爱上海419论坛-阿拉上海后花园419-夜上海最新论坛社区-上海品茶工作室

[This week’s market trend]

From August 12, 2024 to August 16, 2024, the Shanghai Composite Index rose by 0.6% to 2,879.43 points. The growth enterprise market index fell 0.26% to 1591.46 points. The Shenzhen Component Index fell 0.52% to 8349.87 points. () It fell by 0.61% in the last week, rose by 9.40% in the last month and fell by 59.15% in the last year.

[Review of competing products]

[week-related information]

Company news

Zotye Auto became a low-priced stock with a total market value of 8.32 billion yuan.

Summary: 1. Zotye Auto became a "one-dollar stock", and its closing price was lower than that of 1 yuan for 20 consecutive days, so it faced the risk of delisting.

2. Zotye Auto focuses on R&D, manufacturing and sales of complete vehicles, and its products cover multiple market segments.

3. The net profit attributable to Zotye Automobile from 2022 to the first quarter of 2024 was-921 million yuan,-927 million yuan and-124 million yuan respectively.

4. Zotye Automobile has 194,000 shareholders, with a per capita shareholding of 41,300 yuan.

Zotye Auto became a low-priced stock with a total market value of 7.866 billion yuan.

Summary: 1. Zotye Auto’s share price fell for 20 consecutive days, approaching the delisting line in 1 yuan, with a market value of 7.866 billion yuan.

2. Zotye Auto focuses on R&D, manufacturing and sales of complete vehicles, and its products cover multiple market segments.

3. The net profit attributable to Zotye Automobile from 2022 to the first quarter of 2024 was-921 million yuan,-927 million yuan and-124 million yuan respectively.

4. Zotye Automobile has 181,000 shareholders, with a per capita shareholding of 37,500 yuan.

Industry news

Reuters: China led the global sales of electric vehicles to increase by 21% year-on-year in July.

Summary: 1. The market research company Lomoshen said that the global sales of pure electric and plug-in hybrid vehicles increased by 21% year-on-year in July, reaching 1.35 million vehicles. Among them, China has the strongest growth, with a year-on-year increase of 31%, reaching 880,000 vehicles.

2. The demand in Europe is declining, but the strong growth in China is enough to offset this impact.

Janice recalled 1,583 imported G80 and GV80 cars in China, and there were manufacturing problems with the fuel pump impeller.

Summary: 1. Jennisseth Automobile Sales (Shanghai) Co., Ltd. recalled 1,583 imported Jennisseth G80 and GV80, which were produced between August 27th, 2021 and September 8th, 2022, due to the manufacturing problems of fuel pump impellers and potential safety hazards.

2. The company will replace the fuel pump for the vehicles within the recall range free of charge.

[Data] China ranks first! In the first half of 2024, the global sales of hydrogen fuel vehicles decreased by 34.1% year-on-year.

Summary: 1. Hyundai Motor ranked first in the global sales of hydrogen fuel vehicles in the first half of this year.

2. In the first half of 2024, the total sales volume of global registered hydrogen fuel cell vehicles was 5,621, a decrease of 34.1% compared with the same period of last year.

3. NEXO and ELEC of Hyundai Motor

Analysis on the Production and Marketing of New Energy Vehicles in July 2024

Summary: 1. According to the analysis of China Automobile Industry Association, the production and sales of new energy vehicles maintained a rapid growth year-on-year in July 2024.

2. In July 2024, the production and sales of new energy vehicles were 984,000 and 991,000 respectively, up by 22.3% and 27% respectively.

3. From January to July 2024, the production and sales of new energy vehicles were 5.914 million and 5.934 million respectively, up by 28.8% and 31.1% respectively.

4. In July, 2024, the domestic sales volume of new energy vehicles was 887,000, a year-on-year increase of 30.7%.

5. From January to July, 2024, the domestic sales volume of new energy vehicles was 5.226 million, a year-on-year increase of 34.3%.

6. In July 2024, 103,000 new energy vehicles were exported, an increase of 20.6% from the previous month.

7. From January to July 2024, 708,000 new energy vehicles were exported, up 11.4% year-on-year.

BMW Brilliance and BMW (China) recalled some domestic and imported cars.

Summary: 1. BMW Brilliance Automobile Co., Ltd. and BMW (China) Automobile Trading Co., Ltd. recalled some domestic and imported cars, because the driver’s front airbag may be equipped with an ammonium nitrate gas generator without desiccant, which may burst when the airbag is deployed, causing debris to fly out, injuring people inside the car, which is a potential safety hazard.

2. The company will replace it for free to eliminate potential safety hazards.

Tucki’s acquisition of Didi’s smart car business assets is completed, and it is about to enter the "gambling" cashing stage.

Summary: 1. MONA, a mass production vehicle, was produced in Xpeng Motors and delivered to customers. The SOP delivery took place on August 13th.

2. Xpeng Motors will allot and issue 4.64 million Class A ordinary shares to Didi as the consideration shares of SOP, and the related income of Didi’s smart car business has been incorporated into the performance of Tucki.

Mercedes-Benz China recalled some imported E-class and AMG GT cars, totaling 1,716 vehicles.

Summary: 1. Mercedes-Benz (China) Automobile Sales Co., Ltd. recalled 1,716 imported E-Class and AMG GT cars, and the production date was between June 8, 2018 and April 8, 2022, because the electrical connector of the gearbox harness may not be repaired correctly, which may cause fire risk.

2. This recall is another recall of the recall activity on October 21st, 2022. Mercedes-Benz authorized dealers will replace the improved gearbox wiring harness for free.

Janice recalled 1,583 imported Janice G80 and GV80 series cars.

Summary: 1. Jennisseth Automobile Sales Co., Ltd. recalled 1,583 imported Jennisseth G80 and GV80, because the manufacturing problem of fuel pump impeller may lead to flameout in high temperature environment.

2. The company has replaced the fuel pump for free to eliminate potential safety hazards.

Mercedes-Benz (China) Automobile Sales Co., Ltd. recalled some imported cars.

Summary: 1. Mercedes-Benz (China) Automobile Sales Co., Ltd. recalled some imported E-class, S-class and AMG GT vehicles, totaling 1,423 vehicles, and the production date was from February 13, 2017 to July 15, 2022.

2. The connecting hose of the low-pressure fuel pipe may accelerate the aging, resulting in fuel dripping and obvious fuel smell, and there is unreasonable discharge.

3. Mercedes-Benz (China) Automobile Sales Co., Ltd. will replace the connecting hose of low-pressure fuel pipeline and install heat insulation device for free.

4. This recall belongs to the expanded recall of the recall activity released on July 1, 2022.

Chery automobile set up two battery companies.

Summary: 1. Chery Automobile established two battery companies to expand the power battery territory.

2. Deyi Energy has become an important carrier of self-developed batteries, and has landed in two battery project bases, with a planned investment of 28.008 billion yuan.

3. Chery Automobile’s "Eta Ursae Majoris 2025" strategy proposes to launch all () battery products in 2025, and the cruising range will be increased to 1000+ kilometers.

The official interior map of the first model L60 of Weilai Automobile was announced starting from 219,900 yuan.

Summary: 1. The L60, the first model of Ledao Automobile, was officially launched recently, and the official interior map was announced, which is positioned in a medium-sized SUV. The pre-sale price starts at 219,900 yuan and it is expected to be listed in September.

2. The interior design of the new car is simple and generous, equipped with a 17.2-inch 3K retina-level resolution LCD screen with a display ratio of 16:10. The car machine system adopts the global operating system SkyOS of Weilai.

3. In terms of power, the new car is equipped with a battery with a capacity of 60.6 kWh and adopts a single motor or a dual motor drive system.

4. Generally speaking, the L60, the first model of Ledao Automobile, has a brand-new design concept and rich configuration functions, and performs well in riding experience and driving performance. It is expected that this new car will become a dark horse in the market.

BBA’s sales of new energy vehicles plummeted by 30%. People who know cars are more willing to buy domestic cars.

Summary: 1. The price war of new energy vehicles lasted for nearly 600 days.

2. The sales volume of BBA dropped by 30% within two weeks after it withdrew from the price competition.

3. People who know cars are more inclined to buy brands such as domestic new energy vehicles or Tesla, rather than some foreign brands that lack competitiveness and obvious disadvantages.

4. The whole automobile industry is accelerating the transformation to new energy vehicles.

5. The market share of fuel vehicles will be smaller and smaller, and the brand time like BBA is running out.

New energy sales are bleak! South Korea’s electric vehicles cut prices by 29.5%

Summary: 1. In response to the continuous decline in the sales of electric vehicles, large Korean automakers have increased their sales incentives, including Audi, BMW and Hyundai Motor.

2. These measures are regarded as part of the efforts of automobile manufacturers to cope with the possible decline in sales of electric vehicles.

In the first week of March and August, compared with the previous week, the sales of second-hand electric vehicles increased by 184%.

4. From January to July this year, the number of newly registered electric vehicles in Korea was 80,613, a year-on-year decrease of 13.4%.

Sales stall and end-to-end, Xpeng Motors has no way out.

Summary: 1. The organizational structure of Xpeng Motors is adjusted, focusing on the development of end-to-end intelligent driving technology.

2. The XOS 5.2.0 version of Tucki AI Tianji system was released, with over 35 iteration versions every two days.

3. The senior management of Xpeng Motors Zhijia Team continued to "change blood".

Automobile debt: the credit qualification of the industry is neutral, and the brand competitiveness is the core —— The fourth series of reports on the framework of industrial debt

Summary: 1. Automobile industry bonds are supported by science and technology bonds and science and technology bills, and the related bonds of the head company are worthy of attention.

2. Supply structure: Since 2009, the cumulative circulation of the top three automobile entities has accounted for more than one-third of the whole industry.

3. The supply of bond issuance in the automobile industry has declined since 2021. Thanks to the downward interest rate of bond financing and the support of the science and technology variety bond policy, the pace of bond issuance has slightly accelerated.

4. Spread trend: The spread of the automobile industry is highly differentiated, and the spread of middle and low grades is relatively high.

5. The main bodies with a stock of more than 20 billion yuan include Zhejiang Geely Holding Group and Beijing Automotive Group.

Xpeng Motors released a new model Mona M03 to enter the low-end market below 140,000 yuan.

Summary: 1. Xpeng Motors released a new model MONA M03 with a starting price of less than 140,000 yuan, trying to enter the low-end market. () and other new energy automobile giants are their competitors.

2. MONA M03 in Tucki is equipped with the latest advanced intelligent driver assistance system from Tucki, which improves the comprehensive strength in interior design, dynamic performance, endurance and intelligent configuration.

3. However, there are uncertainties in the sinking market, and competitors launch similar models, so Xpeng Motors needs time to verify whether it can succeed.

4. To consider the cost, independent brands need to make a difference in technology, brand and service without raising the price.

Beijing Litong Automobile Consulting Service Co., Ltd. was complained on August 16th, involving a consumption amount of 68,000.00 yuan.

Summary: 1. Beijing Litong Automobile Consulting Service Co., Ltd. was complained by consumers, involving a consumption amount of 68,000.00 yuan. The content of the complaint is that other financial services provided by the company may have personality rights and interests problems (reputation rights), and consumers demand compensation for losses, stop infringement, verify tort liability and apologize.

2. Beijing Litong Automobile Consulting Service Co., Ltd. was established on November 27th, 2014 with a registered capital of RMB 27 million, located at Room 618, Floor 6, Building 8, No.69, Fushi Road, Haidian District, Beijing.

Acquisition of the third largest automobile company in the United States? Byd rumors

Summary: 1. Li Yunfei, General Manager of Brand and Public Relations Department of BYD Group, denied the news that BYD bought Chrysler on the Internet.

2. Chrysler is the third largest automobile company in the United States. It was on the verge of bankruptcy due to the financial crisis and was later acquired by Fiat.

3. GAC Fick went bankrupt due to poor car sales, and the asset auction in the bankruptcy liquidation case was auctioned again because no one bid.

Weifang Jinshitong Automobile Maintenance Service Co., Ltd. won the bid for the ninth vehicle maintenance project of Weifang High-tech Industrial Development Zone People’s Court, with a turnover of 17,488 yuan.

Summary: 1. On August 16th, 2024, the People’s Court of Weifang Hi-tech Industrial Development Zone made nine vehicle maintenance transactions. The supplier of the transaction was Weifang Jinshitong Automobile Maintenance Service Co., Ltd., with a purchase quantity of 7 and a transaction amount of 17,488 yuan.

2. The announcement of this transaction is publicized on the national public resource trading platform.

North America’s automobile capacity utilization rate will drop sharply

Summary: 1. As the automobile industry turns to electric vehicles, the capacity utilization rate of North American automobile factories may fall below 2/3. GlobalData predicts that from 2025, the overall automobile capacity utilization rate in North America will decline again, with an average of 65% in 2030 and 63% in 2035. This is due to the weak demand for electric vehicles and the slow transformation of electric vehicles.

2. According to the data of S&P Global Mobility, in May this year, the number of new car registrations of electric vehicles in the United States increased by about 10% year-on-year, which was much slower than the 52% year-on-year increase in the same period last year.

Automobile price war leads to negative growth, and it is doomed to be short-term only by price involution.

Summary: 1. According to the data of china automobile dealers association Passenger Car Market Information Joint Branch, the retail sales of domestic narrow passenger car market declined in July, down 2.8% year-on-year and 2.6% quarter-on-quarter; The cumulative sales from January to July increased by 2.4% year-on-year.

2. The competition in the automobile market is fierce, the industry is under pressure, and the production and sales are both down year-on-year. The price reduction of some models is "strong", and there are many models involved in the price reduction, which affects the high-quality development of the industry.

3. The profit of the automobile manufacturing industry has been declining year by year, and it has been declining year by year since 2017, with a profit rate of only 4.98%.

4. In the field of intelligent networked new energy vehicles, enterprises will change from competing tomorrow to competing now, and long-term research and development is not important.

5, the car boss "reasonable profit theory" was accidentally injured.

Zu Sijie stepped down as the legal representative of Shanghai Chuangshi Automobile Technology Co., Ltd. and Yan Li took over.

Summary: 1. Zu Sijie, the legal representative of Shanghai Chuangshi Automobile Technology Co., Ltd., stepped down and was replaced by Yan Li.

2. This industrial and commercial change may lead to changes in the person in charge of the enterprise and the shareholding structure, which needs timely attention.

On March 28th, Marvell Perfect Electronics announced that it would show the industry’s first end-to-end optical PCIe 6.0 connection together with TeraHop at the OFC 2025 Optical Fiber Communication Conference and Exhibition which opened on March 30th.

Compared with the traditional electrical PCIe signal transmission,Optical communication has obvious advantages in terms of loss, transmission distance and energy efficiency.It can also unlock a series of new designs, such as physical separation of storage and computing, and is regarded as a feasible scheme for high-speed PCIe communication within AI server clusters in the future. However, due to the traditional use of electrical signals and other reasons, the optical PCIe scheme is still in the early stage.

In this exhibition, the Terahep adapter integrated with Marvell Alaska P PCIe Gen 6 retimer will be used, and the 10-meter TeraHop OSFP-XD active optical cable will be used to transmit signals between the host and endpoint devices.

Marvell saidThis solution can ensure AI accelerator, CPU, CXL pooled memory, SSD and NIC. (IT house note: network card)And realize reliable high-speed connection between them., unlocking new possibilities for the AI-driven data center.

Marvell vice president and general manager of connectivity business department said:

Marvell continues to lead the industry with the first end-to-end optical PCIe Gen 6 connectivity solution, providing the key interconnection technologies needed to expand the AI infrastructure.

With our strong leadership in PAM technology, generations of expertise in PCIe evolution and customized accelerated infrastructure chips, we can help very large enterprises optimize their AI architecture to achieve the highest performance, efficiency and scalability.

　　On July 29th, a white-haired old man and his family sat around a table in the study room of Lianyungang Retirement Center for Retired Cadres in Jiangsu Military Region, solemn and pious. There is a white cake on the red wooden table in front of us, and the bright party flag and the number "92" painted on the cake show the unusual significance of this day.

　　The old man’s name is Zhang Kejing. He is 100 years old. He is an old soldier. This year, in order to celebrate the upcoming 92nd Army Day, he gathered all the children who had joined the army and exercised all over the country to spend a special "birthday" with them. (Correspondent Dong Hongwang, Fan Ting Zi Niu journalist Zhang Lingfei)

　　The 92nd Army Day

　　The younger generation rushed back from all over the country to celebrate.

　　Zhang Ke, who respects the elderly, was born in Bazhou, Hebei Province in April 1919. He joined the army in February 1939 and joined the party in 1942. In the 1960s, the old man came to Lianyungang with the army to settle down. He and his wife participated in War of Resistance against Japanese Aggression, the War of Liberation and the War to Resist US Aggression and Aid Korea, and dozens of military medals on his chest witnessed his glorious years. In 2014, his wife died unfortunately due to illness, and the elderly’s daily life was taken care of by their children in turn.

　　For the elderly people in Zhang Ke, the annual August 1st Army Day is a must. "Before the coming of the Army Day this year, my father wondered if he could call all his children to Lianyungang to celebrate this special festival with him." Zhang Lijun, the fifth son of Zhang Kejing, said.

　　The children of the old man came from all directions immediately after receiving the notice. "The elder sister is from Weihai, the eldest brother is from Qingdao, the second brother is from Xi ‘an, the third brother is from Suzhou, and the fourth brother, my sixth brother and I are all in Lianyungang. Let’s celebrate the 92nd Army Day with the old man."

　　Zhang Xiaoxia, the eldest daughter of Zhang Ke, told Zi Niu news reporter that there are seven brothers and sisters, she is the eldest daughter and the eldest, Zhang Guoqing is her eldest brother, Zhang Zhengping is her second brother, Zhang Haibin is her third brother, Zhang Yuejin is her fourth brother, Zhang Lijun is her fifth brother, and Zhang Mingming is her sixth brother. From 1965 to 1978, seven sisters were sent to the army for exercise by their parents. "My grandfather, grandfather and uncle are all the Eighth Route Army. My parents plus our brothers and sisters, my wife and the younger generation have been in the army for more than a dozen people." Zhang Xiaoxia said proudly. The emergency back, there are seven of their brothers and sisters, and granddaughter (Zhang Guoqing’s daughter) Zhang Na.

　　At 9: 30 in the morning, Zi Niu news reporter saw in the study room of the cadre’s rest home that a red banner was hung on one wall of the room: "Three generations of soldiers greet Bayi", and two tables were set in front of the banner. There was a big cake on the table, with a bright red flag painted on it and the number "92" below the red flag. Later, under the care of their children, the elderly people in Zhang Ke came to the study room to celebrate the August 1st Army Day in advance.

　　Although the old man’s language expression is not so clear, facing the camera, Zhang Ke smiled respectfully and told everyone slowly: "Our good life is given by the party! Long live communist party! Warmly congratulate the 92nd Army Day. "

　　Party age of 77 years

　　Both husband and wife were inspired by Bethune to study medicine to save lives.

　　The Zi Niu news reporter learned that after Zhang Kejing joined the army in 1939, he was sent to Bethune School in Shanxi-Chahar-Hebei Military Region for study in the following year, and worked in the Shanxi-Chahar-Hebei Military Region after graduation. Zhang Kejing joined the Party in 1942.

　　What makes the elderly people in Zhang Ke proud is that his wife Liu Yan once worked with international friend Bethune, and he was once the first student of Bethune School. Influenced by Bethune’s spirit, the couple decided to learn medicine well and save more people. During the war years, their main job was to fight in the front line of rescue with gunfire, and countless comrades-in-arms regained their lives because of them.

　　"Yan Liu and I have been together for 70 years in the Spring and Autumn Period. Under the excellent situation of reform and opening up, our life has become sweeter. Whenever I recall that experience, I feel very emotional in my heart. " Zhang Ke respect for the elderly wrote in his memoirs.

　　Zhang Xiaoxia told Zi Niu news reporter that her mother Yan Liu (formerly known as Li Xiu) joined the army with her grandfather in 1938, because her grandfather was an administrator in the rear hospital of Jizhong Military Region, and her 13-year-old mother studied in the nursing training team of the military hospital after joining the army. In 1939, her mother met Bethune, and once Bethune said in a speech to medical staff, "It is necessary to rescue the wounded in the battlefield quickly. If the wounded are bandaged one minute earlier, the wounded will lose one minute of blood and their lives may be saved." Bethune’s speech has always been engraved on his mother’s mind. My mother worked hard to save the wounded in many battles later, and was not afraid of hardship and fatigue. She was repeatedly rated as a model worker.

　　70 years in the same boat

　　Love in the era of war

　　When it comes to his wife Yan Liu, the dignified expression of Zhang Ke’s respect for the elderly reveals a smile. He wrote in his memoirs: "In 1943, after I returned to the Jizhong Plain with the troops of the Ninth Division of Jizhong, I developed two abscesses because of frequent fighting, hard life and poor sanitary conditions. At that time, Li Xiu (later renamed Yan Liu), a female nurse who changed my dressing, was only seventeen or eighteen years old, with fine features, graceful figure and generous manners. Although she didn’t talk to each other when changing my dressing, I was deeply impressed by her thoughtful service. Since then, her figure has often emerged in my mind. "

　　After the victory of the Anti-Japanese War in 1945, Zhang Ke Jing and Yan Liu were introduced to establish a love relationship. In early 1946, they were married in Xigugang Village, Xidong, Tianjin.

　　With the needs of the war, the Jizhong Military Region established an independent field brigade, and Zhang Kejing was transferred to the health center directly under the brigade, and Yan Liu was also transferred to the institute. It’s a long way to March, sometimes marching hundreds of miles in one night. At that time, Yan Liu was pregnant with their first child. It had been four or five months, and her legs were swollen, but she still walked quickly and never left behind. In the later days, the couple fought with the army in the south and the north, sharing weal and woe and fighting side by side.

　　After the liberation of the whole country, on July 1, 1951, they crossed the Yalu River together to participate in the War to Resist US Aggression and Aid Korea. In order to rescue the wounded on the Korean battlefield, the couple were not afraid of hardship or fatigue. Sometimes they took care of more than 20 wounded people by themselves, carried a stretcher through the enemy blockade and gave their lives to the party and the people until the war was won.

　　"Today’s victory is hard-won. I hope that young people will not forget history and the spirit of hard struggle because they live in peacetime." As he spoke, the old man’s voice choked: "I am very lucky, so many comrades have not seen the victory."

　　Self-improvement all his life

　　Wenchuan earthquake took the lead in donating money, living a simple life and having a strict family style.

　　After retiring, Zhang Kejing and his wife served as the director of the management committee and the old committee for 30 years. They were respected and respected, and each family had a family shortage, so the couple came forward to help solve it. Almost all the activities of the retirement home were planned and organized by the couple.

　　"After the Wenchuan earthquake, the old man took the lead in donating 2,000 yuan, and together with his wife, he sent a special party fee of 6,000 yuan, which made a good start for other comrades." Chen Yan, director of the retired cadres’ office, said, "In fact, for so many years, the elderly have been donating money to those in need every year, but they never like to leave their names."

　　"Parents are self-disciplined, and our education is very strict. At the annual family gathering, my father should read his own family style and family instructions before the younger generation, and give everyone a copy of his family style written by himself. Influenced by them, our brothers and sisters are very friendly, respect and love each other, and always have a grateful heart. " Zhang Kejing’s son Zhang Lijun said.

　　Write down with deep affection: "centenary military salute to the party"

　　Recently, among the elderly, Zi Niu journalists saw a corner of the study full of various honorary certificates of the elderly, while the old man’s desk was full of books and pen and ink. The old man said that he wanted to present gifts to the party and the people’s army in a special way. After that, the old man picked up a writing brush, dipped it in ink, and wrote the seven characters "Centennial military salute to the party" on the paper. Calligraphy is vigorous and powerful, and it has a good demeanor.

　　回顾战争年代的经历，完全可以用“九死一生”来形容。而这个戎马大半生的军人，却在离休后做出了一个“文绉绉”的决定：每天练习毛笔字，把传统文化传承下去。

　　他的儿子张立军经常感慨：“开始以为父亲这项爱好只是突发奇想，没想到他坚持这项兴趣爱好近40年了，直到100岁热情仍不见消退，每天都坚持练两小时。”除了练字，老人的国画也是炉火纯青，一幅《芦雁飞鸣食宿图》惟妙惟肖，十分生动。而且，老人都是自学成才的。

　　“张老爱读书练字，特别喜欢用小楷抄写党的政策方针，装订成册后送给我们这些年轻人阅读。练字除了能传承传统文化，最主要的是能从中感悟到人生哲理，让自己更加豁达开朗，这也许是老人长寿的秘诀吧。”干休所干事陈岩说。

　　知道老人爱书法，海州诗词楹联协会会长朱成安携书法家向张克敬老人送来了楹联书法作品，上面写道：“克敌雄风，今虽百岁军威耀；敬身本色，永是初心国梦追！”这副楹联书法作品，正是老人的真实写照。

Bai Shuangxia is exactly 40 years old this year. She is a supervisor of Jianbei Squadron of Shijiazhuang Digital Urban Management Chang ‘an District Supervision Brigade. She has a slim appearance. Over the years, she has always had a special hobby of "donating blood". Since 2008, she has insisted on voluntary blood donation every year, which lasts for eight years. During an accidental blood donation in 2010, Bai Shuangxia and her lover filled out a voluntary donation of hematopoietic stem cells. She said that at that time, this volunteer letter was not filled in at will, and she felt that she was filling in a responsibility.

Everyone should be familiar with blood donation, but it may be rare to donate hematopoietic stem cells, because the probability of non-blood relationship is only one in ten thousand to one in ten thousand, and the probability of successful blood matching is very low. In March, Bai Shuangxia received a phone call from the Red Cross, saying that a patient had successfully matched her. Bai Shuangxia immediately told the news to her lover and his 15-year-old son. A strange phone call made Bai Shuangxia’s wish buried in her heart come true.

From then on, Bai Shuangxia began to exercise every day to ensure adequate sleep, and her favorite spicy food was also far away. She hoped that her body could be kept in the best condition to better help patients. In her heart, she would do her best to help boys through life difficulties. Bai Shuangxia is the 288th successful donation of hematopoietic stem cells in Hebei Province and the 8th in Shijiazhuang this year. Speaking of donating hematopoietic stem cells, Bai Shuangxia said that she was also influenced by her lover. Now, even her son Xiaobai is infected by his mother’s actions. "When I reach the age, I will also donate blood and register as a volunteer for hematopoietic stem cell donation." Before the bed, her son solemnly and Bai Shuangxia said.

Nowadays, more and more people are paying attention to this great public welfare undertaking, and more healthy people of school age, especially young people, have actively joined the team of donating hematopoietic stem cells, offering "seeds of life" to patients with hematological diseases and helping them get a new life. Life is more meaningful because of the selflessness of donors. They are admirable. Let’s say thank you to this brave, selfless and kind "most beautiful supervisor"!

　　From July 13th to September 26th, National Cultural Heritage Administration Underwater Cultural Heritage Protection Center, Liaoning Provincial Institute of Cultural Relics and Archaeology, and Dalian Institute of Cultural Relics and Archaeology jointly conducted an archaeological investigation on the wreckage of an iron sunken ship in Dalian waters, and confirmed that the ship was a far-off ship sunk by Beiyang Navy in the Sino-Japanese War of 1894-1895. This is another major achievement in underwater archaeology in China after Zhiyuan Ship. After the news was released, it triggered a heated discussion in society. On September 28th, the staff who participated in the archaeology gave more details about the sunken ship passing through the distant ship in the Sino-Japanese War in Dalian waters discovered by the underwater archaeological team.

　　Disappeared for a hundred years, the sinking ship appeared in Dalian waters.

　　The ship that disappeared for more than 100 years was found. Recently, the news released by National Cultural Heritage Administration triggered a hot discussion among netizens. Jingyuan Ship was an important warship of Beiyang Navy in the late Qing Dynasty, which was sunk by the Japanese in the Sino-Japanese War of 1894-1895, and its whereabouts were unknown for more than a century.

　　In the summer of 2014, an underwater archaeological team found the remains of an iron sunken ship in the south sea area of Laorenshi, Heidao, Zhuanghe, Dalian, Liaoning Province based on data clues and magnetometer geophysical data, and speculated that it was a passing ship, but it lacked decisive evidence. Therefore, from July 13th to September 26th this year, National Cultural Heritage Administration Underwater Cultural Heritage Protection Center, Liaoning Provincial Institute of Cultural Relics and Archaeology, and Dalian Institute of Cultural Relics and Archaeology jointly conducted an archaeological investigation on the iron wreck in Dalian waters, and confirmed that the remains of this ship were the Jing Yuan ship of Beiyang Navy.

　　On September 28th, Zhou Chunshui, the leader of National Cultural Heritage Administration Underwater Cultural Heritage Protection Center who participated in the underwater archaeology of the long-distance ship, wrote in official website, National Cultural Heritage Administration that the water depth of the site area was about 10 meters, and the visibility was poor, and the visibility was less than half a meter for a long time during the archaeological period. To this end, the investigation has increased the investment in geophysical exploration technology, and used many technologies such as multi-beam sea survey, three-dimensional imaging and differential positioning.

　　After a hundred years, the name of the ship is still hanging on the side of the ship

　　Zhou Chunshui and others said that this underwater archaeological investigation is divided into two stages. The main goal of the first stage is to search, locate and evaluate the sinking situation. The underwater archaeological team used equipment to collect relic data, and through data comparison and file analysis, combined with diving exploration, searched, found and confirmed the exact position of the passing ship, and found the ring protective armor belt "Tiejiabao" which can mark its identity. At the same time, according to the attitude and inclination of the hull, the hull should be inverted.

　　The goal of the second stage is to partially clean up, so as to confirm the identity of the sunken ship and find out the preservation status of the sunken ship. The underwater archaeological team carried out sand pumping operation on the starboard outer wall of the middle and rear section of the hull, and revealed the hull structure on the side one after another, including gangways, portholes, various pipeline facilities, etc., and all the components were in an inverted state, which confirmed the inference that the hull was upside down.

　　In order to determine the identity of the sunken ship, the underwater archaeological team made a special work plan, and finally found the name of the "Jingyuan" ship buried 5.5 meters below the seabed on September 15, and it has been hanging on the outer wall of the ship’s side for more than 100 years. Underwater archaeologists also unearthed a wooden sign with the word "Jingyuan" stamped on it during the site cleaning. Before the end of the work, the archaeological team covered the wooden ship names and backfilled all the extracted hull areas. Finally, zinc blocks are welded along the periphery of Tiejiabao by sacrificing anodes to delay the corrosion of iron ships by seawater.

　　Traces of fire can be seen in some cultural relics coming out of the water.

　　Zhou Chunshui and others introduced that a large number of relics were extracted from the water in this survey, and more than 500 specimens were selected by archaeologists. Among them, the representative cultural relics include: small iron boilers (providing steam power for windlass hoists), diagonal trusses, large transverse ribs, portholes, hatches, armored fort linings and other hull structural facilities, Mao Se rifle bullets, Weiblie revolver bullets, 37mm Hakikkai rapid-fire shells, 47mm Hakikkai shells. In addition, the archaeologists also found 53mm Grusen gun cartridge and 120mm shell primer, both of which are not found in the factory files of Jingyuan Ship. Archaeologists speculate that it should be an emergency weapon and equipment added before the Sino-Japanese War of 1894 to strengthen the firepower of the stern.

　　Archaeologists also found a "canopy pole" used to hang a sunshade. The wood was covered with fire marks and almost carbonized, which confirmed the theory that Jingyuan ship was hit and caught fire in the naval battle. At the bow of the ship, archaeologists found some hookahs, mahjong tiles, mazars, oil lamps, wooden pots, shoes soles and other items. According to reports, this place is the living quarters of junior soldiers.

　　Archaeologists have found many bullets of Mao Se rifles in the bow area of Jingyuan Ship. It is speculated that this may indicate that at the beginning of the naval battle, the soldiers of Jingyuan Ship had plans to board Japanese warships with guns.

　　"The underwater archaeological achievements of the remote ship have extremely important historical and scientific value for the study of the history of the Sino-Japanese War, the history of the navy and the history of ships. The discovery of some investigation objects provides a new understanding for the research work, such as ‘ Jingyuan ’ The nameplate is the nameplate of the Beiyang Navy warship discovered for the first time, and its material, technology and installation method are also clear for the first time. " Zhou Chunshui and others introduced.

　　conversation

　　Archaeologist: The soldiers who passed the distant ship were heroes who fought to the last minute.

　　Yu Haiming, an underwater archaeologist from Dalian Institute of Cultural Relics and Archaeology, participated in the underwater archaeology of the remote ship. On the 28th, he told the Beijing Youth Daily reporter that the most crucial evidence to prove the true identity of the remote ship — — The "Jingyuan" nameplate was discovered before a typhoon, when archaeology had come to an end. "This is the most shocking moment in the whole archaeological process."

　　Beiqing Daily: How did you participate in this underwater archaeology?

　　Yu Haiming: I completed the training of underwater archaeology from May to June this year, because the sunken warship in this investigation was on Zhuanghe side of Dalian, so I was invited by National Cultural Heritage Administration Underwater Cultural Heritage Protection Center to participate in the investigation of the sunken ship passing through the distant ship in this Sino-Japanese War. I came to the archaeological site of Jingyuan Ship in early July and participated in the follow-up archaeological investigation.

　　Beiqing Daily: You said that your views on Beiyang Navy have changed through this archaeological investigation?

　　Yu Haiming: In the past, we might think that Beiyang Navy was influenced by the Qing Dynasty and had many corruption problems, which led to the defeat of Beiyang Navy in the Sino-Japanese War. Many people who participated in the underwater archaeology this time are very familiar with the history of Beiyang Navy. Every day, everyone works and lives together, and the topic of conversation is Beiyang Navy. They will also take out old photos and materials, and analyze each other together. I feel that my previous views may be misunderstood.

　　It can be seen that Beiyang Navy has been affected by corruption, but the officers and men of Beiyang Navy are indeed heroes. Not only did they fight to the last minute after crossing the distant ship, but in some diaries left by the Japanese army, they also admired the spirit of Beiyang Navy in fighting to the end. A large number of Beiyang Navy officers died in battle or committed suicide.

　　Beiqing Daily: What impressed you the most in this survey?

　　Yu Haiming: What impressed me the most was when the word "Jingyuan" was discovered in the later period of archaeology. The typhoon was coming soon that day. At 6 o’clock in the morning, an archaeological teacher went into the water to investigate. He first photographed the word "far" passing by a distant ship. At that time, the wind and waves were already very heavy, so we asked him to get out of the water quickly. Then everyone looked at the instrument and basically confirmed that the sunken ship must have passed by a distant ship. Later, we successfully found the word "Jing" with gold on it, and everyone was very excited. The identity of Jing Yuan Ship was confirmed like this.

　　Beiqing Daily: How was the wooden sign with the word "Jingyuan" discovered?

　　Yu Haiming: The’ re’ was drawn when pumping sand. There are many things like shells in the pumped sand. During sorting, we found this’ re’ in it. Because when the distant ship sinks, it carries a lot of coal, and these cinders will dye some wooden cultural relics black. This’re like this. At first, I couldn’t see what it was, but I could vaguely see the word "Jing". Then I took this’re "and went to the team leader. According to the experience, the team leader judged that it might be the word "Jingyuan". Later, through some processing, the word "Jingyuan" appeared.

　　Beiqing Daily: What impressed you about the cultural relics coming out of the water?

　　Yu Haiming: Some teachers are very familiar with Beiyang Navy. I found a 120 mm shell primer when sorting cultural relics. I don’t know much about this cultural relic, but one teacher was very excited. He said that this kind of shell itself was not recorded in the equipment of Jingyuan Ship, and it was suspected that it was specially added to prepare for the Sino-Japanese War. It can be seen that Beiyang Navy had actively prepared its combat effectiveness before the war. In addition, unlike some previous legends, we found some hookahs in archaeology, but we didn’t find any big hookahs. The hookahs are normal when sailing on the sea, and we know that we need such a pastime when sailing. This is inconsistent with the previous statement that some Beiyang Navy officers smoked opium.

　　memory

　　The distant ship is a distant ship.

　　Jingyuan Ship is one of the important warships of China Beiyang Navy in Qing Dynasty. It was built by German Vulcan Shipyard and launched on January 3, 1887. It has a length of 82.4 meters (waterline), a width of about 12 meters and a speed of 15.5 knots. Its main weapons include Krupp 210 mm, 2 caliber guns, 2 150 mm caliber guns and 4 torpedo tubes.

　　Jing Yuan Ship returned to China at the end of 1887, and at that time, as the current ship of Zhiyuan Ship, he was incorporated into Beiyang Navy. Deng Shichang and Lin Yongsheng, the famous generals, respectively served as the duct tape (captains) of the two ships. On September 17th, 1894, the Sino-Japanese Sino-Japanese Sino-Japanese War of 1894 broke out in Dadonggou in the northern part of the Yellow Sea. The officers and men of Beiyang Navy fought bravely against Japan, and the Qing army lost four warships in this battle, namely Yang Wei, Chaoyong, Zhiyuan and Jingyuan.

　　In the battle, Zhiyuan and Jingyuan, under the leadership of Deng Shichang and Lin Yongsheng, fought bravely to kill the enemy, but unfortunately they sank successively. Among them, the distant ship was besieged by four Japanese ships, namely Yoshino, Takachiho, Akinzhou and Nobukuro. The officers and men of the whole ship, led by Lin Yongsheng, took up the battle bravely and never raised the flag until their death. There are more than 200 officers and men in the whole ship. Except for more than 10 people who swam to the nearby Old Man Stone to survive, most of them sank with the ship.

　　Zhou Chunshui and others wrote that the Sino-Japanese War of 1894-1895 was a landmark historical event in the modern history of East Asia. For the Qing Empire, this war ended the historical process in which Emperor Guangxu, Li Hongzhang and other upper-level rulers in the late Qing Dynasty tried to realize the rich country of Qiang Bing through the Westernization Movement and naval construction, and China slipped into the abyss of being poor and weak and being trampled upon by others. For the Japanese side, it became famous in the world after the decisive battle and World War I, and finally it was possible to re-examine China as a victor, thus fueling its ambition of conquering China and dominating East Asia. This edition/reporter Qu Chang

　　The transformation of cell fate is determined by precise and complex signal regulation and epigenetic regulation, and the study of its molecular mechanism is one of the core problems that need to be solved urgently in the development of cell biology. Studies have shown that mouse pluripotent stem cells have two different states in signal maintenance and function, namely, primitive Epiblast stem cells, EpiSCs) and naive Embryonic stem cells, ESCs). In vitro, these two kinds of pluripotent stem cells can transform each other. Under the stimulation of ActivinA and bFGF signals, naive ESCs can differentiate into primed EpiSCs. On the contrary, by overexpressing a single naive pluripotent gene, such as Esrrb, Klf2, Nr5a2, etc., the initial to naive transition (PNT) can also be realized. Studying the mechanism of cell fate change in mouse PNT process can provide reference for isolating or inducing naive pluripotent stem cells from different species, but the main molecular mechanism of cell fate change in mouse PNT is still unclear.
　　On May 11th, Pei Duanqing’s research group and Liu Jing’s research group of Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences published a research paper entitled BMP4 resets mouse epi blast stem cells to naive proliferation through zbtb7a/b-mediated chromatin remolding online in the journal Nature Cell Biology. In this study, we first found that BMP4 can induce PNT in mice, and established an efficient PNT induction system with clear components. Subsequently, high-throughput sequencing techniques such as ATAC-seq were used to reveal the specific molecular mechanism of mouse PNT process.
　　At first, researchers found that growth factor BMP4 can induce PNT in mice. With the help of visual reporting system and screening of compound library, it was found that EZH2 inhibitor EPZ6438 and DOT1L inhibitor EPZ5676 can significantly improve the induction efficiency, and then a mouse PNT induction system with a clear chemical composition with an induction efficiency of 80% within 8 days was established.
　　On the basis of this platform, researchers combined bioinformatics analysis based on chromatin transposase accessibility sequencing (ATAC-Seq). The dynamic changes of chromatin accessibility in the process of PNT induced by small chemical molecules in mice were described, and it was found that the most critical factor in this system, BMP4, mediated the progress of PNT by regulating chromatin accessibility, on the one hand, inhibiting the opening of differentiation-related sites, on the other hand, promoting the opening of naive pluripotent gene sites. By analyzing the gene sites where BMP4 opens and activates expression, the researchers found that the new downstream targets of BMP4, Zbtb7a and Zbtb7b, regulate the function of PNT by influencing chromatin remodeling. Furthermore, chromatin immunoprecipitation (Chip) proved that Zbtb7a directly binds to and activates the expression of naive pluripotent genes such as Esrrb, Klf2, Nr5a2, thus regulating the occurrence of PNT.
　　To sum up, this study established an efficient technical platform for chemical induction of mouse PNT, revealed the molecular mechanism and found new targets from the perspective of chromatin accessibility, and made new discoveries in the study of cell fate transformation mechanism, which provided a new understanding and breakthrough point for the study of chemical regulation of cell fate transformation, and also provided a very meaningful reference direction for other research systems, such as the acquisition of naive pluripotent stem cells in human system.
　　Researchers Pei Duanqing and Liu Jing are the corresponding authors of this paper. Doctoral students Yu Shengyong and Zhou Chunhua, Ph.D. students Cao Shangtao and He Jiangping are the co-first authors of this paper.
　　Paper link
　　Cell fate transition process, chromatin changes and intervening regulatory proteins

Recently, a group of renderings of M8, which were drawn by a car blogger according to the patent drawings, have a high similarity with the final vehicle products. The front face design of Wenjie M8 adopts a zigzag daytime running light, and the middle decorative plate can be lit at the edge, and the logo stands in it, so the overall shape is simple and atmospheric. The Xinghe design of vehicles is an important symbol to distinguish different levels of vehicles. The higher the level, the brighter the Xinghe. There is no "Xinghe" area in the M7, while the M8 has a full side shape, and the tail design is a reduced version of M9. The size of the light group is reduced, and the license plate frame is moved down. The first model chose the color scheme of "Purple Gas from the East", which added a sense of fantasy.

The front face design of the M8 is different, which is considered as a design strategy to prevent "one loss and one loss" and spread risks. Bloggers predict that the M8 in the world may be positioned at the level of 300,000 yuan, and the price is between M7 and M9. The design and positioning of this model have attracted the attention and discussion of the market.

　　Beijing, January 30th, 2007 (Reporter Chang Yafei of the Central Television Station) Recently, there was a picture circulating on the Internet: the central government required "returning home from a low-risk area with a green code", but in the province, it became "negative proof of nucleic acid test", in the city, it became "home isolation", in the town, it became "nucleic acid proof+centralized isolation+home isolation", and in the village, it became "please leave gracefully". The reporter’s interview and investigation found that although this picture on the Internet has deductive elements, it is also a reflection of the facts at the grassroots level. Especially in some places, the epidemic prevention policy is "overweight" or even "one size fits all".

　　On January 27th, at the press conference of the joint prevention and control mechanism in the State Council, Zhao Chenxin, secretary-general and spokesman of the National Development and Reform Commission, and Zeng Yixin, deputy director of National Health Commission, proposed that all localities should not be allowed and do not want to make "one size fits all" treatment when implementing the relevant policies formulated by the state for returning home for the New Year, and should not block people from traveling and returning home, but should give more protection and convenience to the people. What problems did the "Spring Festival returnees" encounter? Why is the "return home policy" being "overweight" in implementation?

　　National Health Commission recently issued the Notice on Printing and Distributing the Work Plan of COVID-19 Epidemic Prevention and Control in Rural Areas in Winter and Spring (hereinafter referred to as the Notice). The "Notice" clarifies that returnees need to return home with a negative result of effective nucleic acid test within 7 days, and implement home health monitoring for 14 days after returning home, during which they will not gather or flow, and carry out nucleic acid testing every 7 days. On January 14th, Xiao Li returned to a low-risk area in Benxi City, Liaoning Province from nangang district, a low-risk area in Harbin, with a negative report of nucleic acid test. When he returned to the village, he was asked to stay at home for 7 days.

　　Xiao Li told reporters: "Normally, those who return home from low-risk areas and have negative reports of nucleic acid testing can move at home normally without isolation. However, our village said that according to the superior’s opinion, I was still quarantined at home for 7 days. However, after the expiration of 7 days of isolation, no one gave me a nucleic acid test, and there were no measures and guarantees during the isolation process. In fact, it was a mere formality. "

　　Xiao Li said that because of the recurrence of the epidemic in Heilongjiang Province, his colleague Xiao Zhang returned to a low-risk area in his hometown of Hubei for 10 days and was isolated in his hometown. He said: "He had already returned home for about 10 days, and there were sporadic cases in Heilongjiang, so the local government asked them to concentrate on isolation again. From the day he came home, he was not released until 14 days after the quarantine expired. Not all of Hubei is like this, but only some parts of Hubei, such as a certain district or a certain township. This is actually the grassroots blindly pursuing prevention and control effects in the process of prevention and control without considering the actual situation. "

　　Mr. Wang from Shanghai recently returned his high-speed train ticket to his hometown in Jiaozuo, Henan. He said that in mid-January, he paid attention to his hometown’s policy of returning home. He learned from the neighborhood Committee that people returning from low-risk areas only need to provide proof of nucleic acid testing within 7 days and then monitor their health at home. He also took the initiative to declare his trip to the neighborhood Committee. But I didn’t expect that the feedback policy of the neighborhood Committee changed two days later: when he returned from Shanghai, he needed to be isolated at his own expense.

　　Mr. Wang said: "My mother called me and said that people in the community came to tell me that if I went back, I would go to the designated hotel for 14 days at my own expense. There is no point in going back like this, because the annual leave is only seven days. This is a soft way to let you not come back. "

　　Ms. Zhou from Anqing City, Anhui Province told the Voice of China reporter that she had planned to go back from Shanghai to visit her grandmother with a cerebral infarction during the Spring Festival, but because the community where her hometown is located requires that she be isolated at home for 14 days and have a nucleic acid test every seven days. Ms. Zhou calculated that the second nucleic acid test after returning home coincided with the date of the doctoral examination, and the neighborhood Committee stressed that the date of nucleic acid could not be revised, so she had to stay in Shanghai.

　　"Even if the nucleic acid testing, why can’t we reschedule? Wouldn’t it be nice to advance or postpone one day? But the people in the neighborhood Committee kept saying ‘ No ’ . In the process of talking to the staff of the (neighborhood) Committee, I found it hard to accept what she said. She said, ‘ I don’t care if you are low-risk or what kind of risk, as long as you come to us, that’s it. ’” Ms. Zhou said.

　　Requirements of returning home for epidemic prevention and control in Anqing City, Anhui Province

　　The "overweight" epidemic prevention policy has also been corrected in some places.

　　On January 24th, a village in Linxi County, Xingtai, Hebei Province issued a notice forbidding villagers working outside to go home for the New Year. After being reported by the media, the village secretary said that there was something wrong with the statement of the notice, but he just hoped that the villagers outside would try not to go home and had corrected the notice. Some netizens also reported that in Taocheng District, Hengshui City, Hebei Province, residents’ committees or property requirements, if they have to return to Hengshui under special circumstances, need to report to the community residents’ committees for registration in advance. After the personnel arrive, they will be isolated for 14 days at their own expense. After media reports, residents’ committee staff said that they had received orders from their superiors to cancel the notice. At present, the requirement is to carry out nucleic acid testing twice within 3 days after returning home, and to monitor the physical condition at home during this period, and not to go out unless necessary.

　　Regarding the deformation of the policy of returning home during the Spring Festival in some areas, Yang Hongshan, a professor at the School of Public Administration of Renmin University of China, told the Voice of China reporter that this is a manifestation of insufficient refined management in some places. He said: "The relationship between epidemic prevention and control, local resumption of production and normal production and living order is actually a parallel relationship, not a one-way choice relationship. Therefore, we can see that in today’s local epidemic situation, maybe our place needs to take care of all aspects. Simply considering only one factor and pursuing absolute safety or absolute self-exemption may also be a manifestation of insufficient initiative and meticulous management in some places. In the process of operation, the basic top-down epidemic prevention and control policies and related laws and regulations are sometimes ignored by grassroots governments. "

　　Yang Hongshan believes that it is necessary to attract the attention of local governments through media publicity and reports, so as to urge them to take corresponding measures in time to stop the "overweight" epidemic prevention and control behavior. Local governments should adopt differentiated management by regions and levels, and pay more attention to "embroidery" and human feelings.

　　"Today, in the face of big data, there is also a collaborative management mechanism between different regions. It is necessary to take the clues of the epidemic itself as the guide, and adopt refined prevention and control measures for local and sporadic epidemics. In the case of complete control, just for the convenience of one’s own work, regardless of the convenience of the other party, and completely ignoring the interests and rights of the other party, it is actually a bit simple and rude, and it is also a manifestation of not taking measures according to people’s policies in local governance. The more you are in the grass-roots governance, the more you face the vivid reality, and the more you know all kinds of differentiated situations. In fact, in the process of grassroots governance, it is more necessary to consider the human touch. " Yang Hongshan said.

Original Wuyuan Li Na and other SIFIC infection horizons　

Author: Wu Yuan Li Na Jin Wenting Ma Yuyan

Review: Hu Bijie and Pan Jue

First, a brief introduction to medical history

Male, 63 years old, from Shanghai, was admitted to the Infectious Diseases Department of Zhongshan Hospital for the second time on November 23, 2022.

Chief complaint: indwelling catheterization with repeated urine color turbidity for 2 months and then 8 days.

Current medical history:

On September 19, 2022, I went to a hospital in Shanghai for fatigue, anorexia and dysuria. WBC 10.12×10 9/L, N 87.6%, Hb 53g/L, hsCRP 135.22mg/L, ESR 62mm/H, albumin 30.1g/L, Scr 589μmol/L, K 2 were examined. Urine routine: WBC 3892/ul, occult blood 3+/RBC 5579/ul, protein 2+; Chest CT: bilateral pleural effusion, partial atelectasis of lower lobe of both lungs; Abdominal pelvic CT: Bilateral middle and upper ureteral dilatation and renal pelvis and calyceal dilatation, the patch in the right part of calyceal is slightly high density, the bladder wall is thickened, there is a little flocculent blur around the left renal fat sac and ileocecal part, and there is a little effusion in the pelvic cavity. A large amount of turbid urine was drained by indwelling catheter. Urine culture showed that Klebsiella pneumoniae was positive. Considering urinary tract infection, acute kidney injury, hypokalemia and severe anemia, patients were given symptomatic support treatment such as anti-infection, bladder irrigation, antioxidation, potassium supplementation and blood transfusion. The symptoms of patients improved and the urine was slightly clarified. 10-18 Review urine routine: WBC3+, RBC3+, protein 1+, SCR 263 μ mol/L.

I was admitted to our department on October 19, 2022. Blood routine: WBC 5.08X10 9/L, N 66.1%, inflammatory markers: ESR 19mm/H, hsCRP 52.3mg/L, PCT 0.52ng/ml, Scr 257μmol/L, and urine routine: WBC 28493/μ. Urinary color Doppler ultrasound: hydronephrosis, bilateral ureteral dilatation, bladder wall thickening significantly; Abdominal pelvic CT: hydronephrosis of both renal pelvis and ureter, thickening of ureter wall (inflammatory change), inflammatory change of bladder and ureter may be large, the volume of both kidneys increases and the substance is thin. Meropenem 1g q12h is given for empirical anti-infection. Urology consultation considers the acute stage of infection, so it is not suitable to put double J tubes. If necessary, pyelostomy can be done, but it does not improve renal function much. Bladder irrigation is recommended. 10-20 middle-stage urine culture (sampling on October 19): Klebsiella pneumoniae was positive; 10-22 urine culture drug sensitivity: Carbapenem-resistant Klebsiella pneumoniae (CRKP), adjusted to ceftazidime and abamectin 2.5g q12h for anti-infection, and daily bladder irrigation. After treatment, the urine color of the patients gradually became clear, and the urine white blood cell and bacterial count gradually decreased during follow-up. The urine bacterial culture was negative on November 1 and November 4. Check the urine routine on November 09: WBC 28/uL, RBC 4/uL, urine protein+,bacterial count 29/UL;Blood WBC 7.64×10 9/L, N 76.5%, hs-CRP 0.4mg/L, ESR 25mm/H, PCT 0.18ng/mL, Scr 175μmol/L, which were significantly improved compared with those at admission. Stop ceftazidime and abamectin on November 11 and be discharged.

On November 15, 2022, the patient appeared turbid urine again, and there was no fever and other discomfort. On November 23, he was admitted to the hospital for a second diagnosis and treatment.

Past history: In September, 1991, T12-L1 comminuted fracture was treated with internal fixation. After operation, the catheter was retained for half a year due to urinary incontinence, and then the catheter was removed after urination. There was no urinary tract infection during this period. Diabetes for 16 years, insulin therapy, blood sugar control can be; Hypertension for 5 years, oral amlodipine to reduce blood pressure, blood pressure control can be.

Second, the admission examination (admitted on November 23, 2022)

[physical examination]

T: 36.2℃ P: 90 times/min R: 20 times/min BP: 176/105 mmHg.

Stay in bed, feel refreshed and calm, lose weight, and muscle atrophy of lower limbs; Breathing sounds in both lungs are thick, and dry and wet rales are not heard; The rhythm of the heart is regular, the abdomen is soft, without tenderness and rebound pain, without mass, without percussion pain in both kidneys, without tenderness at ureter point and rib and waist point, and the lower abdomen does not touch the enlarged bladder. During indwelling catheterization, the urine in the urine collection bag is turbid and more white flocs are deposited. Limbs are not swollen.

[Laboratory examination]

Blood routine: WBC 7.85×10 9/L, N 81.3%, HB 121g/L, PLT 170×10 9/L.

Urine routine: WBC 2775/μ l; RBC 2/μl, bacterial count: 39879/μl, nitrite positive, leukocyte esterase+++.

Inflammation markers: hs-CRP 17.9mg/L, ESR 68mm/H, PCT 0.12ng/mL.

Biochemistry: ALT/AST 23/21U/L, Alb 47g/L, Scr 199μmol/L, eGFR 30ml/min/1.73m2, na/k 140/5.5mmol/l.

Third, clinical analysis

Characteristics of medical history: middle-aged and elderly male, indwelling catheter, with repeated urinary turbidity and abnormal urine routine. Urine culture showed CRKP one month ago, and it improved after ceftazidime-ababactam treatment, but urine turbidity reappeared three days after drug withdrawal, blood inflammatory index increased, urinary leukocyte and bacterial count increased significantly, and the diagnosis of urinary tract infection was clear. The reasons for short-term recurrence after antibacterial drug treatment improved were considered:

Recurrence of CRKP infection: The patient has been indwelling catheter for 2 months, and there may be biofilm formation of catheter and abnormal urinary tract structure, which makes it difficult to completely eliminate the infection and relapse after stopping taking the drug. Therefore, urine culture and drug sensitivity test can be improved.

New infection: the patient has high risk factors of recurrent urinary tract infection, and the pathogen may be different each time. The patient’s previous CRKP infection treatment was effective, and the possibility of new pathogen infection should be considered in the short term, until the urine culture is perfect and clear.

Multiple infections: patients with abnormal urinary tract structure, indwelling catheter and other risk factors can not be removed, so it is necessary to be alert to the possibility of multiple pathogens including fungi combined with infection, repeat the cultivation of urine bacteria, mycoplasma, fungi and mycobacteria, and improve urine mNGS to help clarify the infected pathogens.

Four, further examination, diagnosis and treatment process and treatment response

On November 23, 2022, the middle urine smear was used to find bacteria: moderate amount of G- bacilli, and continued ceftazidime and abamectin 2.5g q12h ivgtt for anti-infection and bladder irrigation.

On November 26, 2022, the bacterial drug sensitivity of the middle-stage urine culture (sampling on November 23) was CRKP, ≥ 100,000 /ml, and urine mNGS: a large number of Klebsiella pneumoniae (species strict sequence number: 406,866) was detected.

On November 29, 2022, the abdominal and pelvic CT was reexamined: bilateral dilated hydronephrosis accompanied with inflammatory changes of ureter, and the parenchyma of both kidneys was thin, and the inflammatory changes of cystitis might be larger, similar to that of 22-10-20 slices.

November 30, 2022 (sampling on November 29): Enterococcus faecalis was positive. On December 2, according to the drug sensitivity, fosfomycin 3g qod was added orally, and ceftazidime and abamectin were suspended.

Repeated urine cultures on March, April and June, December, 2022: Enterococcus faecalis was positive and CRKP was negative.

On December 8, 2022, the urine WBC was 38738/μ L, and the bacterial count was 43285/μ L; Urine culture: CRKP positive, Enterococcus faecalis negative.

Phage therapy was carried out from the afternoon of December August, 2022: Phage cocktail (composed of 5 strains of Klebsiella pneumoniae phages A103KP172, A106KP176, A121KP192, A49KP106 and A58KP118, 5mL each), injected with 225mL physiological saline (according to the estimated bladder volume), and the total volume was 250mL, and then the catheter was clamped.

Urine routine on the third day of phage treatment on December 11, 2022: white blood cell count: 235/uL, bacterial count: 722/uL；; Urine bacterial culture was negative.

Urine routine on the 5th day of phage therapy on December 13th, 2022: white blood cell count: 279/uL, bacterial count: 92/ul; Urine bacterial culture was negative; Blood WBC 6.35X109/L, N 70%, hs-CRP 0.9mg/L, ESR 26mm/H, and inflammatory index decreased compared with before; Re-examination of urinary color ultrasound showed that bilateral renal pelvis separation and upper ureteral dilatation were better than before (10-20), and the thickness of bladder wall was reduced (12-25mm→13mm).

He was discharged from hospital on December 14, 2022 for follow-up.

V. Final diagnosis and diagnosis basis

Final diagnosis:

Complex urinary tract infection (CRKP, Enterococcus faecalis)

Neurogenic bladder, hydronephrosis and hydroureter (indwelling catheter)

Renal insufficiency

Diagnostic basis:

The patient is a middle-aged and elderly male with neurogenic bladder caused by paraplegia, indwelling catheter, turbid urine with flocs, increased CRP and PCT, significantly increased WBC and bacterial count in urine, repeated CRKP positive in urine culture, positive in enterococcus faecalis, abdominal basin CT: hydronephrosis of renal pelvis and ureter, anti-infection, normal inflammatory markers and urine routine after phage treatment, clear urine and negative urine culture, so complicated urinary tract infection.

The patient suffered from anorexia and dysuria, and the serum creatinine increased obviously. Abdominal CT showed that both kidneys were enlarged, the cortex was thin, and bilateral urinary tract was hydronephrosis. After active treatment such as controlling infection and improving renal function, the serum creatinine decreased, so the diagnosis of renal insufficiency was clear.

Six, experience and experience

Phage is a targeted sterilization virus in nature and a sterilization star in the "pre-antibiotic era". Phage therapy has a history of more than 100 years, but the discovery and application of broad-spectrum antibiotics have gradually marginalized it. With the increasingly serious problem of bacterial drug resistance, phages have once again received attention and become the most promising supplement and alternative therapy for treating superbugs. The clinical application of phage in China is relatively late, but it has developed rapidly in recent years. In 2017, the Shanghai Institute of Phage and Drug Resistance was established, with Professor Hu Bijie as an academic member. Since 2018, the institute has carried out the first clinical trial of phage therapy in China. At present, it has treated nearly 100 patients with drug-resistant bacterial infections from all over the country and accumulated rich clinical experience in phage therapy, which is a leading position in the field of clinical phage therapy in China.

Phage has many advantages, such as host bacteria dependence, targeted specific sterilization, no infection to eukaryotic cells (little influence on normal flora), no influence on bacterial drug resistance, synergy with antibacterial drugs, penetration of biofilm and so on. The cure rate of acute bacterial infection is high, and the therapeutic effect of chronic bacterial infection is no less than that of antibacterial drugs, and the safety of phage treatment is also extremely high. A systematic retrospective study showed that the vast majority of patients who received phage therapy had no or only slight adverse reactions, 86.7% patients’ clinical symptoms improved, and 78.8% patients achieved the eradication of pathogenic bacteria. Our clinical trials also show that more than 70% of patients have achieved good therapeutic effects, and there are no obvious cases of adverse reactions. This patient was repeatedly infected with Klebsiella pneumoniae due to long-term paraplegia, abnormal urinary tract structure, indwelling catheter and other factors. The diagnosis of complicated urinary tract infection was unquestionable, and the choice of antibacterial drugs was limited due to multi-drug resistance and renal insufficiency. Phage therapy is very suitable.

The disadvantages of phage therapy include narrow host spectrum, individualized plan (it is difficult to treat empirically), no unified standard for the best treatment decision, and rapid tolerance. Phage cocktails, combined antibacterial drugs and multiple treatments are usually used in clinic to improve the curative effect. At present, the targeted pathogens of phage therapy in our team mainly include: multi-drug resistant Gram-negative bacteria (Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecalis); Covering respiratory system, urinary system, abdominal cavity, bones and joints, skin and soft tissue and other infected sites; Treatment depends on the site of infection, and intravenous application of phage is still being explored. In this case, the patient didn’t have percutaneous nephrostomy because of the little clinical benefit, so he was treated by transurethral bladder perfusion, and the phage could not cover the whole urinary tract evenly. Although the pathogen turned negative in a short period of time and was well tolerated, its long-term curative effect may not be good, and it needs repeated phage treatment.

Phage therapy has huge clinical demand and broad market. In recent years, our team has focused on the clinical application (treatment and prevention and control of nosocomial infection) and basic research of phage therapy, with a view to becoming a powerful weapon to curb drug-resistant bacteria in the future.

references

[1] Uyttebroek S, Chen B, Onsea J, Ruythooren F, Debaveye Y, Devolder D, Spriet I, Depypere M, Wagemans J, Lavigne R, Pirnay JP, Merabishvili M, De Munter P, Peetermans WE, Dupont L, Van Gerven L, Metsemakers WJ. Safety and efficacy of phage therapy in difficult-to-treat infections: a systematic review. Lancet Infect Dis. 2022 Aug; 22(8):e208-e220.

[2] Chegini Z, Khoshbayan A, Taati Moghadam M, Farahani I, Jazireian P, Shariati A. Bacteriophage therapy against Pseudomonas aeruginosa biofilms: a review. Ann Clin Microbiol Antimicrob. 2020 Sep 30; 19(1):45.

[3] Lusiak-Szelachowska M, Weber-Dabrowska B, Gorski A. Bacteriophages and Lysins in Biofilm Control[J]. Virol Sin, 2020,35(2):125-133.

Every Monday night

The Department of Infectious Diseases of Zhongshan Hospital affiliated to Fudan University in Shanghai will be with you!

Photo: Xiaoxiao

Original title: "Detective Case: The Nemesis of Super Bacteria is Coming"

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　　February 4th is the 17th World Cancer Day, and this year’s theme is "WE CAN, I CAN". The member of the Standing Committee of Cancer Radiotherapy Committee of China Anti-Cancer Association and the president of Cancer Hospital said: At present, 70% of cancer patients in our city are in the middle and late stage when they are diagnosed, so it may be a better choice for them to eliminate the fear of cancer and realize coexistence with cancer.

　　70% of cancer patients need to live with tumors.

　　Mr. Luo, who lives in Yubei District, is 55 years old. He is used to working from nine to five every day. If no one tells him, no one will think that he is actually a cancer patient. Five years ago, he suddenly felt that he was always urinating, but he couldn’t urinate. At first, he thought he was getting angry. But a pile of heat-clearing drugs didn’t improve after eating, and the more urgent the urine, the less smooth it was, and sometimes it was accompanied by pain. At this time, he thought about going to the hospital for examination.

　　I didn’t want to be diagnosed with prostate cancer and have bone metastasis. I have lost the best opportunity for surgery and can only use antiandrogen drugs to control my condition. In the face of cancer, he did not intend to give up, but actively cooperated with the treatment. After one year, his condition gradually stabilized, and Mr. Luo began to plan to go to work in the unit.

　　Professor Dean of the Municipal Cancer Hospital said that according to the "2015 China Cancer Statistics" issued by the National Cancer Center, there were 4.3 million new cancer cases in China in 2015, and the number of cancer deaths exceeded 2.8 million; In Chongqing, there were about 80,000 new tumors and more than 50,000 cancer deaths in 2014. Because the incidence of tumor is relatively concealed, more than 70% of cancers are found in the middle and late stages, and the best opportunity for surgical treatment is lost. For them, survival with tumor may be a better choice.

　　Unfortunately, in real life, there are not many patients who can scientifically understand the survival with tumors like Mr. Luo. As soon as many patients heard that they could not operate, their spirits suddenly collapsed and they thought they were hopeless. In fact, surgical treatment is not the only treatment for all tumors; Even if we miss the best opportunity for surgical treatment, it doesn’t mean that there is no cure. At present, tumor treatment advocates comprehensive treatment, which includes surgery, chemotherapy, radiotherapy, endocrine therapy, traditional Chinese medicine treatment and other ways. Experienced specialists will choose the appropriate treatment according to the results of tumor pathological examination, course of disease and development trend.

　　"It is very important for cancer patients and their families to accept" survival with tumor ",which is a more pragmatic method for treating advanced cancer." Dean said that cancer is essentially a genetic disease, and all cancers come from genetic mutation, which is caused by genetic mutation and epigenetic regulation. At present, human beings can’t use drugs to reverse this genetic mutation and "kill all cancer cells" in the body.

　　It is also a pragmatic choice for patients in the middle and late stage to realize long-term "survival with tumor" and "peaceful coexistence" with tumor. Everyone should treat it as a medical disease with disease, and treat tumor as a chronic disease such as hypertension, diabetes and coronary heart disease, which is more conducive to treatment.

　　The misunderstanding of survival with tumor needs to be vigilant

　　There may be many people who don’t understand that living with a tumor is not cured. There is a tumor in the body, and the condition may deteriorate at any time. Can this be safe? Dean Wu Yongzhong said that in fact, survival with tumor is not to let it go, but to choose a suitable treatment model, which is also the core of "individual medicine" developed from "evidence-based medicine" in recent years. First of all, we should recognize the fact that the dream of conquering tumor has not been realized.

　　WHO has regarded tumor as a chronic disease, because its condition has a process of development, which can not be cured and exists for life, just like diabetes, hypertension and coronary heart disease. Secondly, sometimes over-active treatment is also a kind of injury. In clinic, some elderly cancer patients are often encountered. When children hear that they can have surgery and treat at all costs, they have not achieved good results. This is because the elderly, especially those over 80 years old, have degraded their physical functions and cannot tolerate surgery and chemotherapy at all.

　　At this time, you don’t have to think about eliminating the tumor at all. You can choose radiotherapy alone or other treatments, so as to survive with cancer. Advocating survival with tumor again also means waiting for treatment conservatively. If it can be cured by surgical resection, radiotherapy and other treatment methods, tumor patients should still be encouraged to actively treat.

　　Age-related macular degeneration (AMD) mostly occurs in people over the age of 50, and it is one of the main blinding diseases of the elderly in the world. According to statistics in 2010, there are more than 23 million AMD patients worldwide. The patient’s chief complaint is decreased vision, which is characterized by the absence of central visual field (see schematic diagram).

　　Normal visual field (left), central visual field damage caused by AMD (right)

　　Age-related macular degeneration can be divided into Dry AMD and Wet AMD. Dry amd is characterized by no vascular proliferation, while wet amd is characterized by obvious vascular proliferation in macular area. There is almost no treatment for dry age-related macular degeneration, while wet age-related macular degeneration is mainly aimed at vascular proliferation. For vascular proliferation, Genentech’s Ranibizumab (trade name: Lucentis) is a fragment antibody against VEGFA, and it costs two thousand dollars for a shot. However, many places bypass Ranibizumab and choose Avastin (Avastin), which is also anti-VEGF, for only fifty dollars. It can be seen that there are policies and countermeasures, which are available to people at all times and all over the world, but the interests are accelerating. In addition, laser therapy is also aimed at vascular proliferation. Although there is symptomatic treatment for vascular hyperplasia, it is also a temporary solution, because macular degeneration itself has not improved.

　　A core problem of macular degeneration is degeneration of retinal pigment epithelial cells (RPE). These cells are close to the interlayer between Choroid and optic nerve cells in retina, and are responsible for bringing blood nutrition to optic nerve cells. If this layer of cells degenerates, the optic nerve cells will not get nutrition, so the vision will decrease. There’s an old saying in China, what can I do without fur? Is the image explanation of this disease.

　　A remarkable pathological feature of macular degeneration is yellow sediment distributed on the retina, which is a mixture of protein and lipid, but its source is unknown, and it may be an inflammatory product, and its pathological function is to destroy retinal pigment epithelial cells (RPE). See the figure below.

　　Since it is a degenerative disease, the research and development of drugs lacks molecular targets, which are a bit like Alzheimer’s disease and neurodegeneration, and there are not many effective targets. In contrast, the stem cell technology that surfaced in the past ten years is an ideal choice. Stem cells are induced to differentiate into retinal pigment epithelial cells (RPE), which provides a feasible and effective method for the treatment of macular degeneration.

　　Can normal retina replace diseased retina? A few decades ago, someone replaced the diseased retina with the baby’s retina (of course, the source was the baby who died in a car accident under two years old), and the success rate was very low, because the source of newborn retina was difficult, the protection was difficult, and the operation was difficult, which were all restrictive factors. However, some people have gained some vision (such as light perception and figure) through retinal replacement. This scheme can at least prove that infant retinal replacement is a direction that can be improved. However, it is not successful to replace the bad eye retina with the good eye retina of the same adult, which shows that the physiological age of retina is an important reason. Nowadays, retinal pigment epithelial cells (RPE) can be produced from stem cells, whether from embryonic sources (hESC) or from self-induced sources (iPSC), and they can be made into Sheet, which is beneficial to surgical implantation. Of course, there are many technical problems, mainly the problem of eye surgery and the problem of ensuring the survival of cells after implantation. A positive factor is that the eye is an immune escape, so don’t use immunosuppressants, immune rejection should be small, which is conducive to survival.

　　Regenerative medicine is a new field, and big pharmaceutical companies are unwilling to take this risk. Seven years ago, the author worked in the world’s largest ophthalmic pharmaceutical company (Allergan) and once recommended this project, but the decision makers are interested in Miu Miu. At present, several small companies have pushed the application of regenerative medicine in senile macular degeneration into the clinical stage. Although I dare not predict when it will be approved by the FDA, it is still expected as a promising direction. After all, there is no other way at present. Although the experiment of regenerative medicine is still in the "primary stage of socialism", the AMD market is very large, and there are still some large and medium-sized pharmaceutical companies to follow up. Not long ago, Astra, the second largest pharmaceutical company in Japan, bought Ocata Therapeutics LLC to jointly develop this method for treating AMD, which mainly focuses on hESC inducing retinal pigment epithelial cells (RPE).

　　Regenerative medicine is not only dedicated to age-related degenerative macular degeneration (AMD), but also can be used to treat another cause of blindness, Retinal pigmentosa. It also damages retinal pigment epithelial cells (RPE), but retinal pigment degeneration damages peripheral visual field, and other eye diseases such as glaucoma and corneal burn. In order to give you a big picture of regenerative medicine in treating ophthalmic diseases, the author summarizes the general situation of some companies entering clinical trials at present. I sincerely hope that these companies can succeed in regenerative medicine and bring good news to patients with ophthalmic diseases.

　　Table 1. Summary of Clinical Trials of Regenerative Medicine in Treating Ophthalmic Diseases