Cell Stem Cell: dopaminergic progenitor cells derived from human embryonic stem cells in the treatment of Parkinson’s disease

Original biological world

Written by Cong Wang

Edit Wang Duoyu

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Cell therapy is considered to be very suitable for treating Parkinson’s disease (PD) because its pathogenesis is relatively simple and characterized by localized degeneration of dopaminergic neurons in the substantia nigra compacta of the midbrain. In animal experiments and human experiments, transplanting human fetal ventral midbrain tissue or cells has been proved to help restore motor function.

However, these results are often inconsistent, which highlights the need for improved cell therapy programs to ensure that a sufficient number of well-defined midbrain dopaminergic (mDA) neurons are produced and standardized cell preparation and transplantation procedures are adopted.

Recent technological progress has enabled human pluripotent stem cells (hPSC), such as embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC), to efficiently generate mDA neurons, paving the way for establishing transplantation therapy for Parkinson’s disease based on hPSC. Many studies have shown that when transplanted into animal models of Parkinson’s disease, mDA progenitor cells derived from hPSC are well integrated into the host brain and mature into functional mDA neurons, which significantly improves motor function.

Recently, researchers from Yonsei University School of Medicine published a research paper entitled: preclinical and dose-ranging assessment of HESC-derived dopaminergic prognosticators for a clinical trial on Parkinson’s disease [1].

In this study, high-purity midbrain dopaminergic (mDA) progenitor cells were produced on a large scale from clinical human embryonic stem cells (hESC), and the safety and effectiveness of mDA progenitor cells were verified in vitro and in vivo. MDA progenitor cells improved the disease-related behavior of Parkinson’s disease rat model in a dose-dependent manner. Based on these preclinical research results, the research team obtained the approval of the Korean Ministry of Food and Drug Safety for the phase 1/2a clinical trial of cell therapy for Parkinson’s disease, and started the treatment of 12 patients with Parkinson’s disease.

In May, 2020, researchers at Massachusetts General Hospital reported a groundbreaking study in the New England Journal of Medicine (NEJM) [2]. A Parkinson’s patient who received autologous transplantation of mDA progenitor cells from hiPSC showed stable or improved clinical symptoms 24 months after implantation. Now, this method has been further developed, and the mDA progenitor cells derived from hiPSC and hESC began to enter the early clinical trial stage.

The first step in the clinical application of cell transplantation for Parkinson’s disease is to define the characteristics of cell products comprehensively. It is very important to determine whether cells are produced with clinical grade materials under GMP conditions and whether they meet the expected clinical use standards. Subsequently, preclinical research should produce convincing evidence of curative effect through large-scale animal experiments, and systematically examine long-term safety-related issues, such as toxicity, biological distribution and tumorigenicity. In addition, preclinical research needs to determine the optimal cell dose range for transplantation as a reference for human trials. Most importantly, the whole research design must be meticulous and the results must be evaluated in a fair way. This usually requires cooperation with CRO and extensive discussions with regulators.

This paper describes the process and results of a preclinical study aimed at using midbrain dopaminergic (mDA) neurons derived from human embryonic stem cells (hESC) in human clinical trials to treat Parkinson’s disease.

The cell differentiation method used in this study has been optimized for clinical application to ensure that it meets GMP standards. This optimization method can produce mDA progenitor cells with high purity and low temperature preservation on a large scale, while maintaining strict quality control. A year-long large-scale transplantation study by an independent CRO company using immunocompromised rats showed that the transplanted mDA neurons did not cause tumorigenicity, significant toxicity or ectopic integration outside the injection site. In addition, clinical mDA precursor cells showed therapeutic potential and dosage range, and produced therapeutic effects in toxin-induced semi-Parkinson’s rats. These findings provide the necessary information about the appropriate cell dose for human trials.

Specifically, this paper introduces the method of large-scale extraction of high-purity mDA progenitor cells from clinical grade hESC under strict GMP conditions, and also evaluates the toxicity, biological distribution and tumorigenicity of these cells in immunocompromised rats in facilities conforming to good laboratory practices (GLP). Different doses of mDA progenitor cells were transplanted into the semi-Parkinson’s rat model, and it was observed that there was a significant dose-dependent behavior improvement when the minimum effective dose ranged from 5000 to 10000 mDA progenitor cells. These results provide insights for determining the low cell dose (3.15 million cells) in human clinical trials.

Based on these experimental results, the research team obtained the phase 1/2a clinical trial of cell therapy for Parkinson’s disease approved by the Korean Ministry of Food and Drug Safety, and started the clinical trial of treating patients with Parkinson’s disease.

Paper link:

1. https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00401-0

2. https://www.nejm.org/doi/10.1056/NEJMoa1915872

Read the original text

In 2019, the national economy was generally stable, and the annual GDP increased by 6.1% year-on-year. The per capita disposable income of residents exceeded 30,000.

  CCTV News:According to the website of the National Bureau of Statistics, on January 17, the National Bureau of Statistics released the operation of the national economy in 2019.

  According to preliminary accounting, the gross domestic product for the whole year of 2019 was 99,086.5 billion yuan, an increase of 6.1% over the previous year at comparable prices, in line with the expected target of 6%-6.5%. Quarterly, it increased by 6.4% in the first quarter, 6.2% in the second quarter, 6.0% in the third quarter and 6.0% in the fourth quarter. In terms of industries, the added value of the primary industry was 7,046.7 billion yuan, up by 3.1% over the previous year. The added value of the secondary industry was 38,616.5 billion yuan, an increase of 5.7%; The added value of the tertiary industry was 534.233 billion yuan, an increase of 6.9%.

  First, the grain output reached a record high, and the growth of cattle, sheep, poultry, eggs and milk was realized.

  In 2001, the total national grain output was 663.84 million tons, up by 0.9% over the previous year, with an increase of 5.94 million tons, which remained above 650 million tons for five consecutive years. Among them, the output of summer grain was 141.6 million tons, an increase of 2.0%; The output of early rice was 26.27 million tons, down by 8.1%; The output of autumn grain was 495.97 million tons, up by 1.1%. In terms of varieties, the wheat output was 133.59 million tons, an increase of 1.6%; The corn output was 260.77 million tons, an increase of 1.4%; Soybean output was 18.1 million tons, up by 13.3%. The annual output of pigs, cattle, sheep and poultry was 76.49 million tons, down 10.2% from the previous year. Among them, the beef output was 6.67 million tons, an increase of 3.6%; The output of mutton was 4.88 million tons, an increase of 2.6%; The output of poultry meat was 22.39 million tons, an increase of 12.3%; The output of poultry eggs was 33.09 million tons, an increase of 5.8%; The milk output was 32.01 million tons, up by 4.1%; The output of pork was 42.55 million tons, down by 21.3%.

  Second, industrial production continued to develop, and high-tech manufacturing and strategic emerging industries grew rapidly.

  The added value of industrial enterprises above designated size increased by 5.7% over the previous year. In terms of economic types, the added value of state-owned holding enterprises increased by 4.8%; Joint-stock enterprises increased by 6.8%, and foreign-invested enterprises from Hong Kong, Macao and Taiwan increased by 2.0%; Private enterprises increased by 7.7%. In terms of three categories, the added value of mining industry increased by 5.0%, manufacturing industry increased by 6.0%, and electricity, heat, gas and water production and supply industries increased by 7.0%. The added value of high-tech manufacturing and strategic emerging industries increased by 8.8% and 8.4% respectively over the previous year, and the growth rate was 3.1 and 2.7 percentage points faster than that of industries above designated size. In December, the added value of industrial enterprises above designated size increased by 6.9% year-on-year, 0.7 percentage points faster than the previous month and 0.58% higher than the previous month. In December, the manufacturing purchasing managers’ index (PMI) sub-index, the production index, new order index and supplier delivery time index were 53.2%, 51.2% and 51.1%, respectively, all above the critical point. The expected index of manufacturing production and operation activities is 54.4%, which is located in a high boom zone.

  From January to November, the total profits of industrial enterprises above designated size in China reached 5,610.1 billion yuan, down 2.1% year-on-year, and the decline rate was 0.8 percentage points narrower than that in January-October. In November, the total profits of industrial enterprises above designated size increased by 5.4% year-on-year, and decreased by 9.9% in October.

  Third, the service industry developed rapidly, and the modern service industry grew well.

  The national service industry production index increased by 6.9% over the previous year. The added value of information transmission, software and information technology services, leasing and business services, finance, transportation, warehousing and postal services increased by 18.7%, 8.7%, 7.2% and 7.1% respectively, and the growth rate was 11.8, 1.8, 0.3 and 0.2 percentage points faster than that of the tertiary industry respectively. From January to November, the operating income of service enterprises above designated size increased by 9.4% year-on-year. Among them, the operating income of strategic emerging service enterprises, science and technology service enterprises and high-tech service enterprises increased by 12.4%, 12.0% and 12.0% respectively, and the growth rate was 3.0, 2.6 and 2.6 percentage points faster than that of all service enterprises above designated size. The operating profit of service enterprises above designated size increased by 3.5%.

  In December, the business activity index of service industry was 53.0%, which remained above threshold. Among them, the business activity index of railway transportation, accommodation, telecommunications, broadcasting, television and satellite transmission services, Internet software and information technology services, financial services, leasing and business services industries are all in the higher boom zone of more than 55.0%. From the market expectation, the expected index of service business activities is 59.1%, which shows a good growth momentum.

  Fourth, the market sales grew steadily, and the proportion of online retail sales increased significantly.

  The total retail sales of consumer goods in the whole year was 41,164.9 billion yuan, an increase of 8.0% over the previous year. Among them, the retail sales of consumer goods above designated size was 14.801 billion yuan, an increase of 3.9%. According to the location of business units, the retail sales of urban consumer goods was 35,131.7 billion yuan, an increase of 7.9%; The retail sales of rural consumer goods reached 6,033.2 billion yuan, an increase of 9.0%. According to consumption types, catering revenue was 4,672.1 billion yuan, up by 9.4%; Retail sales of commodities reached 36,492.8 billion yuan, up by 7.9%. Consumption-upgrading commodities grew rapidly. The growth rate of retail sales of cosmetics, communication equipment, sports and entertainment goods, household appliances and audio-visual equipment above designated size was 8.7, 4.6, 4.1 and 1.7 percentage points faster than that of retail sales of consumer goods above designated size. In December, the total retail sales of social consumer goods increased by 8.0% year-on-year and 0.53% quarter-on-quarter.

  In 2001, the national online retail sales reached 10,632.4 billion yuan, an increase of 16.5% over the previous year. Among them, the online retail sales of physical goods was 8,523.9 billion yuan, up by 19.5%, accounting for 20.7% of the total retail sales of social consumer goods, up by 2.3 percentage points over the previous year.

  5. Investment in fixed assets grew steadily, while investment in high-tech industries grew rapidly.

  In the whole year, the investment in fixed assets (excluding farmers) was 55,147.8 billion yuan, an increase of 5.4% over the previous year. In terms of fields, infrastructure investment increased by 3.8%, manufacturing investment increased by 3.1%, and real estate development investment increased by 9.9%. The national commercial housing sales area was 1,715.58 million square meters, down by 0.1%; The sales of commercial housing reached 15,972.5 billion yuan, up by 6.5%. By industry, investment in the primary industry increased by 0.6%, investment in the secondary industry increased by 3.2%, and investment in the tertiary industry increased by 6.5%. Private investment was 31,115.9 billion yuan, an increase of 4.7%. Investment in high-tech industries increased by 17.3%, 11.9 percentage points faster than the total investment, among which investment in high-tech manufacturing and high-tech service industries increased by 17.7% and 16.5% respectively. Investment in social fields increased by 13.2%, 7.8 percentage points faster than the total investment, among which investment in education, culture, sports and entertainment increased by 17.7% and 13.9% respectively. In December, fixed asset investment increased by 0.44% month-on-month.

  6. Foreign trade grew against the trend, and the proportion of general trade continued to increase.

  The total import and export volume of goods in the whole year was 31,544.6 billion yuan, an increase of 3.4% over the previous year. Among them, exports were 17,229.8 billion yuan, up by 5.0%; Imports reached 14,314.8 billion yuan, up by 1.6%. Import and export balance, with a surplus of 2,915 billion yuan. The import and export of general trade accounted for 59.0% of the total import and export, an increase of 1.2 percentage points over the previous year. The export of mechanical and electrical products increased by 4.4%, accounting for 58.4% of the total export. China’s import and export to EU and ASEAN increased by 8.0% and 14.1% respectively. With the countries along the Belt and Road, the import and export growth is good. The total import and export growth of countries along the Belt and Road is 10.8%, which is 7.4 percentage points higher than the growth rate of total import and export of goods. In the whole year, industrial enterprises above designated size realized export delivery value of 12,421.6 billion yuan, an increase of 1.3% over the previous year.

  Seven, consumer prices rose in line with the expected target, and industrial producer prices declined slightly.

  The annual consumer price rose by 2.9% over the previous year, in line with the expected target of about 3%. Among them, cities rose by 2.8% and rural areas rose by 3.2%. By category, the prices of food, tobacco and alcohol rose by 7.0%, clothing by 1.6%, housing by 1.4%, daily necessities and services by 0.9%, transportation and communication by 1.7%, education, culture and entertainment by 2.2%, medical care by 2.4% and other goods and services by 3.4%. Among the food, tobacco and alcohol prices, the price of grain rose by 0.5%, the price of fresh vegetables rose by 4.1%, and the price of pork rose by 42.5%. The core CPI excluding food and energy prices rose by 1.6%, down 0.3 percentage points from the previous year. In December, consumer prices rose by 4.5% year-on-year, which was the same as last month. The ex-factory price of industrial producers decreased by 0.3% over the previous year, and decreased by 0.5% in December, which was the same as last month. The purchase price of industrial producers decreased by 0.7% over the previous year, and by 1.3% in December, which was the same as last month.

  Eight, the employment situation remained stable, and the urban survey unemployment rate met the expected goal.

  In the whole year, 13.52 million new jobs were created in cities and towns, which remained above 13 million for seven consecutive years, significantly higher than the expected target of over 11 million, and 122.9% of the annual target was achieved. In December, the national urban survey unemployment rate was 5.2%. In 2019, the national urban survey unemployment rate remained between 5.0% and 5.3%, achieving the expected goal of less than 5.5%. The unemployment rate of the population aged 25-59, the main employment group in China, is 4.7%. In December, the survey unemployment rate in 31 big cities and towns was 5.2%. At the end of 2019, the urban registered unemployment rate was 3.62%, 0.18 percentage points lower than the end of the previous year, which was in line with the expected target of less than 4.5%. At the end of the year, there were 774.71 million employed people in China, including 442.47 million employed people in cities and towns. The total number of migrant workers in the year was 290.77 million, an increase of 2.41 million or 0.8% over the previous year. Among them, there were 116.52 million local migrant workers, an increase of 0.7%; There were 174.25 million migrant workers, an increase of 0.9%. The average monthly income of migrant workers was 3,962 yuan, an increase of 6.5% over the previous year.

  Nine, the income growth of residents and economic growth are basically synchronized, and the ratio of per capita income of urban and rural residents continues to shrink.

  In the whole year, the per capita disposable income of the national residents was 30,733 yuan, a nominal increase of 8.9% over the previous year, and the growth rate was 0.2 percentage points faster than that of the previous year; After deducting the price factor, the real growth rate was 5.8%, which was basically in sync with the economic growth and roughly the same as the per capita GDP growth. According to the permanent residence, the per capita disposable income of urban residents was 42,359 yuan, a nominal increase of 7.9% over the previous year, and a real increase of 5.0% after deducting the price factor; The per capita disposable income of rural residents was 16,021 yuan, a nominal increase of 9.6% over the previous year, and a real increase of 6.2% after deducting the price factor. The per capita income ratio of urban and rural residents was 2.64, 0.05 lower than that of the previous year. The median per capita disposable income of the national residents was 26,523 yuan, a nominal increase of 9.0% over the previous year. Divided into five equal income groups, the per capita disposable income of the low-income group is 7380 yuan, the per capita disposable income of the lower middle income group is 15777 yuan, the per capita disposable income of the middle income group is 25035 yuan, the per capita disposable income of the upper middle income group is 39230 yuan, and the per capita disposable income of the high income group is 76401 yuan.

  In the whole year, the per capita consumption expenditure of the national residents was 21,559 yuan, an increase of 8.6% in nominal terms over the previous year, and the growth rate was 0.2 percentage points faster than that of the previous year. After deducting the price factor, it actually increased by 5.5%. According to the place of permanent residence, the per capita consumption expenditure of urban residents was 28,063 yuan, a nominal increase of 7.5%; The per capita consumption expenditure of rural residents was 13,328 yuan, a nominal increase of 9.9%.

  Ten, key reforms and tackling key tasks have been solidly promoted, and the economic transformation and upgrading trend has continued.

  The structural reform of the supply side has achieved remarkable results. In 2019, the national industrial capacity utilization rate was 76.6%, an increase of 0.1 percentage points over the previous year; Among them, the capacity utilization rates of oil and gas exploitation, ferrous metal smelting and rolling processing industries were 91.2% and 80.0%, respectively, up by 2.9 and 2.0 percentage points over the previous year. The asset-liability ratio of enterprises has declined. At the end of November, the asset-liability ratio of industrial enterprises above designated size was 56.9%, down 0.3 percentage points year-on-year. At the end of the year, the area of commercial housing for sale nationwide was 498.21 million square meters, down 4.9% from the end of the previous year. The unit cost of enterprises continued to decline compared with the beginning of the year. In terms of short board, investment in weak links has grown rapidly. The investment in ecological protection and environmental management, environmental monitoring and management services increased by 37.2% and 33.4% respectively, which was 31.8 and 28.0 percentage points faster than the total investment. The vitality of micro-subjects is enhanced. In 2019, there were 23.77 million newly registered market entities and 20,000 newly registered enterprises per day, with an activity rate of about 70%. At the end of the year, the total number of market entities reached 120 million. Key progress has been made in the three major battles. In the whole year, 11.09 million rural poor people were lifted out of poverty. According to preliminary accounting, the proportion of clean energy consumption such as natural gas, hydropower, nuclear power and wind power in total energy consumption increased by 1.0 percentage points over the previous year; The energy consumption per 10,000 yuan of GDP continued to decline over the previous year, with a decrease of 2.6%. At the end of November, the national local government debt balance was 21,333.3 billion yuan, which was within the limit approved by the National People’s Congress.

  The economic structure continued to be optimized. The added value of the tertiary industry accounted for 53.9% of GDP in the whole year, up 0.6 percentage points from the previous year and 14.9 percentage points higher than that of the secondary industry. The contribution rate to GDP growth is 59.4%. The role of consumption as the main driving force of economic growth has been further consolidated, and the contribution rate of final consumption expenditure to GDP growth is 57.8%, which is 26.6 percentage points higher than the total capital formation. Upgrading and upgrading residents’ consumption. The Engel coefficient of national residents was 28.2%, down 0.2 percentage points from the previous year. In the annual per capita consumption expenditure of national residents, service consumption expenditure accounted for 45.9%, up 1.7 percentage points over the previous year.

  Eleven, the total population grew steadily, and the urbanization rate continued to increase.

  At the end of the year, the total population of Chinese mainland (including active servicemen of 31 provinces, autonomous regions, municipalities directly under the Central Government and the People’s Liberation Army of China, excluding Hongkong, Macao Special Administrative Region, Taiwan Province and overseas Chinese) was 1,400,005, an increase of 4.67 million over the end of last year. The annual birth population was 14.65 million, and the birth rate was 10.48&permil. ; The death population was 9.98 million, and the population mortality rate was 7.14‰ ; The natural population growth rate is 3.34‰ . From the perspective of gender structure, there are 715.27 million males and 684.78 million females, and the sex ratio of the total population is 104.45 (100 females). In terms of age composition, the working-age population aged 16 to 59 is 896.4 million, accounting for 64.0% of the total population; The population aged 60 and over is 253.88 million, accounting for 18.1% of the total population, of which 176.03 million are aged 65 and over, accounting for 12.6% of the total population. From the perspective of urban and rural structure, the permanent population of cities and towns is 848.43 million, an increase of 17.06 million over the end of last year; The rural resident population was 551.62 million, a decrease of 12.39 million; The proportion of urban population in the total population (urbanization rate) was 60.60%, an increase of 1.02 percentage points over the end of last year. The population with separated households (that is, the population whose residence and household registration are not in the same township street and have left the household registration for more than half a year) is 280 million, a decrease of 6.13 million compared with the end of last year; Among them, the floating population is 236 million.5.15 million fewer than the end of last year.

  On the whole, in 2019, the national economy continued to maintain a generally stable, steady and progressive development trend. At the same time, we should also see that the current world economic and trade growth is slowing down, the sources of turmoil and risk points are increasing, domestic structural and institutional cyclical problems are intertwined, and the downward pressure on the economy is still relatively large. In the next stage, we must adhere to the guidance of the Supreme Leader’s Socialism with Chinese characteristics Thought in the new era, follow the decision-making arrangements of the CPC Central Committee and the State Council, adhere to the general tone of striving for progress through stability, adhere to the new development concept and promote high-quality development, adhere to the supply-side structural reform as the main line, persist in taking reform and opening up as the driving force, resolutely win the three tough battles, do a good job in the "six stabilities" work in an all-round way, and make overall plans to promote steady growth, promote reform, adjust the structure, benefit people’s livelihood, prevent risks and ensure stability.

Don’t push the flu. Don’t delay these symptoms!

Influenza is called "influenza" in Chinese. Because of the word "cold" in it, many people think that it is a CommonCold, and they take it lightly, but in fact, getting the flu may cause serious consequences and even be life-threatening.

According to WHO estimates, influenza can cause 3 million to 5 million severe cases and 290,000 to 650,000 respiratory disease-related deaths worldwide every year. A global research data estimated the mortality of 33 countries from 1999 to 2015, and estimated the average annual influenza-related mortality as follows:

pneumonia

The most common complication of influenza

Clinically, people younger than 5 years old, older than or equal to 65 years old (there are also guidelines to limit them to more than 50 years old), pregnant women, people with chronic basic diseases within 2 weeks after delivery are listed as high-risk groups for complications. The risk of influenza complications in healthy young people is low, but the risk cannot be ignored.

Pneumonia is the most common complication of influenza, and its typical manifestations are cough with dyspnea, rapid breathing (> 24 beats/min), hypoxia and fever (> 3 days). Types of pneumonia include:

Primary influenza virus pneumonia: high fever persists 3 ~ 5 days after the onset of influenza, and there are the above pneumonia manifestations. It is usually very serious, and the progress may be rapid. Without active intervention, it will be life-threatening, especially for people with lung or cardiovascular diseases.

Secondary bacterial pneumonia: After the flu symptoms have improved (including fever), fever and expectoration occur again. It usually occurs a few days after the flu (7 ~ 14 days), and it is the most common, accounting for about 1/3 of severe flu. The secondary staphylococcus aureus pneumonia is often critical.

Bacterial and viral mixed infectious pneumonia: referring to the above two, it can be manifested as gradual aggravation of symptoms, or it can be manifested as aggravation after a short improvement.

These flu complications should also be noted.

In addition to pneumonia, influenza and these complications should also be careful:

Cardiac complications: myocardial ischemia, myocardial infarction and heart failure, accounting for about 12% of adult influenza, but influenza myocarditis and pericarditis are rare.

Complications of central nervous system: Seizures are more common in children and epileptic patients, and influenza-related encephalopathy is more common in children. Influenza causes adult encephalitis, cerebrovascular accident, acute disseminated encephalomyelitis and Guillain-Barre syndrome, which is not common in general.

Musculoskeletal complications: severe myositis and rhabdomyolysis (extreme myalgia, weakness and dark urine color) are more common in children. Although myalgia is a prominent feature of influenza, real myositis is not common.

Toxic shock: During the outbreak of influenza A and B in recent years, toxic shock-like syndrome appeared in previously healthy children and adults, mostly related to secondary infection.

Co-infection: including pneumonia (other viruses, bacteria and fungi), bacteremia, meningitis and aspergillosis. For influenza patients who have a fever for more than 3 ~ 5 days, have a fever again after the fever has gone down, or the symptoms continue to worsen after 3 ~ 5 days, they need to be vigilant.

What is the flu?

What’s the difference with the common cold?

Common cold symptoms

The typical common cold is usually characterized by runny nose and obvious nasal congestion. Other common symptoms include dry throat, itching or pain, cough and discomfort. Adult colds rarely have fever or low fever. Cough is more common, often appearing after symptoms of nasal congestion and runny nose; Nasal secretions may be thin or purulent (not necessarily bacterial infection).

flu symptoms

The biggest difference between flu and common cold lies in its severity. Different people have different symptoms after being infected with the flu. Mild symptoms are similar to colds, and severe ones will have the complications mentioned above.

Taking the flu lightly may lead high-risk groups to ignore vaccination or timely use of antiviral drugs, which may lead to serious and irreversible consequences. For example, due to neglect of vaccination, influenza causes serious comprehensive diseases, resulting in the death of children; For the elderly, this problem may be more hidden, but in clinic, we can often see that a seemingly ordinary cold may lead to a sharp decline in the physical condition of the elderly, or even inability to return to the sky.

It is sometimes not very accurate to distinguish flu from cold from symptoms. The quickest and most accurate method is pathogen detection. In clinic, if it is necessary to identify what kind of virus causes a cold, the methods can include virus culture, antigen detection and PCR. However, if there is no way to detect it in time, with the development of the disease, there may still be some differences in symptoms between the two:

Worldwide, influenza causes a large number of hospitalizations and deaths every year, which is a serious public health problem. Even for healthy adults, severe pain may occur after influenza infection, and the resulting temporary labor loss or quality of life decline is even more intense.

What should I do after I get the flu?

A self-judgment

For young people (15-65 years old) who are usually healthy, when they have flu cases in their own communities, schools, offices, etc., and suddenly have symptoms of fever, cough, myalgia or weakness, they can be clinically suspected of flu.

At this time, no flu test is needed to confirm the diagnosis. Home testing of self-purchased antigens is also an option, but due to the influence of sampling technology, the positive accuracy may not reach the expected 50% ~ 70%. When it is necessary to make a definite diagnosis, multiple sampling within 1 ~ 2 days will help to improve the positive accuracy.

With uncomplicated influenza, fever and respiratory symptoms of adults usually last for about 3 days, and then most of them will improve. It may take 10 ~ 14 days to fully recover (the recovery time is longer for the elderly and immunocompromised), and fatigue symptoms of some patients will last for several weeks.

Influenza with complications, or dehydration (thirst, fatigue, low urine yellow), impaired cardiopulmonary function, and mental state change are usually severe and should be hospitalized.

B When the flu is suspected or confirmed, it meets any of the following conditions and needs active antiviral treatment:

High-risk group of complications: antiviral treatment is recommended for influenza in high-risk groups, regardless of the severity of symptoms and whether the course of disease exceeds 2 days.

Contacts of high-risk groups: non-high-risk groups have influenza, but they will come into contact with high-risk groups (such as children and the elderly at home). No matter the severity of symptoms and whether the course of disease exceeds 2 days, antiviral treatment is also recommended.

Persistent or severe influenza: Influenza-like symptoms continue to progress for more than 3 days, or when influenza complications or severe influenza occur. It is recommended to follow the doctor’s advice and choose the corresponding antiviral drugs for timely treatment when the disease is severe or the course of disease exceeds 2 days.

C does not belong to the above three situations. Before taking medicine, weigh the pros and cons: the course of disease is within 48 hours, and you can decide whether to give antiviral treatment according to your own needs in life, work or study, because mild influenza can heal itself, and drugs can shorten the course of disease, but at the same time increase the risk of drug resistance.

If the course of the disease has been more than 48 hours and does not meet the above three requirements, antiviral treatment is not recommended.

Focus

Influenza can be very harmful, which can easily lead to serious complications, especially fatal to high-risk groups. Therefore, we must pay attention to influenza vaccination!

September and October are usually good times to get the flu vaccine every year, but even if you don’t get the vaccine before the end of October, you can get it throughout the flu season. Moreover, because the influenza virus is prone to mutation, the influenza epidemic strain may change every year, so the influenza vaccine should be vaccinated every year!

Push forward the grand cause of Chinese modernization.

  Building a modern and powerful country and realizing the great rejuvenation of the Chinese nation is the grand goal that the Communist Party of China (CPC) people are striving for, which embodies the lifelong efforts of the older generation of revolutionaries such as Comrade Mao Zedong. In his important speech at the symposium commemorating the 130th anniversary of Comrade Mao Zedong’s birth, General Secretary of the Supreme Leader spoke highly of Comrade Mao Zedong’s great achievements for the Chinese nation and the people of China, profoundly expounded that Comrade Mao Zedong’s lofty spiritual demeanor is a powerful driving force to inspire us to move forward, and solemnly declared that the best commemoration for Comrade Mao Zedong is to push forward the cause he started. On the new journey, we must not forget our initial intention, keep our mission in mind, strengthen our historical self-confidence and grasp the historical initiative, and constantly push forward the grand cause of Chinese modernization. Studying and implementing the spirit of the important speech of the Supreme Leader General Secretary is of great significance for us to maintain our political strength, strengthen our confidence in winning, strengthen our responsibility, continue to push forward the cause initiated by Comrade Mao Zedong and other revolutionaries of the older generation, adhere to the Socialism with Chinese characteristics road, and create a new situation of Chinese modernization.

  1. Promote the great rejuvenation of the Chinese nation in the continuous struggle.

  General Secretary of the Supreme Leader pointed out: "Comrade Mao Zedong’s life is a life of unremitting struggle for national prosperity, national rejuvenation and people’s happiness." Chinese modernization is the result of long-term practice and exploration by the people of the Communist Party of China (CPC) and China. Comrade Mao Zedong, as the great founder of China’s socialist modernization, has been striving for the modernization of China, a country with a very backward level of social productive forces. Facing the backward situation of the semi-colonial and semi-feudal society in old China, Comrade Mao Zedong and other revolutionaries of the older generation led our party and led the people of China to fight bloody battles and persevere, found the correct path of the new-democratic revolution, completed the historical task of anti-imperialism and anti-feudalism, established People’s Republic of China (PRC), established the basic socialist system, promoted socialist construction, and realized the most extensive and profound social changes in the history of the Chinese nation. It has made great achievements in socialist construction, laid a fundamental political premise and institutional foundation for all the development and progress of contemporary China, and accumulated important experience in socialist construction in a country with a very backward level of social productive forces, such as China. Comrade Mao Zedong and other revolutionaries of the older generation have made great and fundamental contributions to the cause of socialist modernization in China, which will never be forgotten in the history of the Chinese nation and in the hearts of all China people.

  The great practice of revolution, construction and reform led by our Party is a historical process of continuous struggle and a complete cause of saving the country, rejuvenating the country and strengthening the country, thus realizing the great rejuvenation of the Chinese nation. Comrade Mao Zedong and other revolutionaries of the older generation led the people of China to make great achievements in revolution and construction, which not only provided a solid foundation and institutional guarantee for Chinese modernization, but also enabled the new China to build an independent and relatively complete industrial system and national economic system from "a car, an airplane, a tank and a tractor" to "two bombs and one satellite" and nuclear submarines. China has completely got rid of the danger of being expelled from football and become a big country with important influence in the world, thus laying an important foundation for China to embark on the road of reform and opening up, create Socialism with Chinese characteristics and successfully promote and expand the road of Chinese modernization. It is the central task of the whole party and people of all nationalities in the new era and new journey to comprehensively promote the construction of a strong country and the great cause of national rejuvenation with Chinese modernization. This is the unfinished business of Mao Zedong and other revolutionaries of the older generation, and it is the solemn historical responsibility of contemporary the Communist Party of China (CPC) people. In the new era and new journey, we should firmly grasp the central task of the Party, inherit the historical aspirations of the older generation of revolutionaries such as Comrade Mao Zedong, carry forward the historical initiative spirit, and work hard together with Qi Xin to ensure that the great ship of the Chinese nation will ride the wind and waves and make steady progress.

  2. Chinese modernization is the socialist modernization led by the Communist Party of China (CPC).

  General Secretary of the Supreme Leader pointed out: "the Communist Party of China (CPC), created by Comrade Mao Zedong personally, has been maturing in revolutionary forging, and has always been at the forefront of the times, becoming the backbone of the people of the whole country and the strong leadership core of China’s revolution, construction and reform." The leadership of the Party is directly related to the fundamental direction, future and destiny, and ultimate success or failure of Chinese modernization. In China, a country with a majority of farmers and backward economy and culture, how to build an advanced proletarian political party, how to lead China’s revolution and construction, and how to arm the party and the people’s army with proletarian ideology are the primary problems encountered in China’s revolution and construction. In the process of leading China’s revolution and construction, Comrade Mao Zedong always attached great importance to strengthening Party leadership and Party building, calling it a "great project" and leading the people of China to forge a great, glorious and correct the Communist Party of China (CPC). Comrade Mao Zedong closely combined Marxism–Leninism’s theory of party building with the Communist Party of China (CPC)’s self-construction practice, and always took strengthening the party’s leadership as a major issue, emphasizing that "the party leads everything in seven aspects: industry, agriculture, commerce, learning, military, politics and the party"; Emphasize that "the Communist Party of China (CPC) is the core of the leadership of the people of China. Without such a core, the socialist cause cannot be won. " Comrade Mao Zedong, as the main founder of our party, has always attached great importance to all aspects of party building and put forward the basic principles of ideological party building.Grasping party building as one of the three magic weapons, scientifically clarifying the relationship between party building and the party’s political line, strengthening party building through rectification, and actively exploring a series of major principles and principles for the construction of the ruling party have provided valuable experience and ideological wisdom for in-depth exploration of what kind of party to build in China, how to build the party and how to realize party leadership, and how to continue to build a strong Marxist ruling party in the great cause of Socialism with Chinese characteristics.

  Party, government, military and civilian studies, east, west, north and south, the party is the leader of everything. The Party is the highest political leading force. Comrade Mao Zedong attaches great importance to the party’s leadership and party building, proposes and advocates the purpose of serving the people wholeheartedly, formulates discipline rules such as "three major disciplines and eight attentions", takes a clear-cut stand against subjectivism, sectarianism and stereotyped Party writing, calls on the whole party to bear in mind the "two musts", emphasizes opposing bureaucracy, being an official, preventing the decline of revolutionary will, resolutely punishing corruption, etc., and defines party building and managing the party and governing the party in a certain historical stage. General Secretary of the Supreme Leader pointed out that the leadership of the Party determines the fundamental nature of Chinese modernization. Only by unswervingly adhering to the leadership of the Party can Chinese modernization have a bright future and flourish. To promote Chinese-style modernization in the new era and new journey, we must adhere to a series of glorious traditions and fine styles of strengthening party leadership and party building, keep in mind the "three musts", persistently promote the comprehensive and strict management of the party, implement the general requirements of party building in the new era, guide all the work of party building with party political construction, improve the comprehensive and strict management system of the party, and promote it as a whole to ensure that our party will never deteriorate, change color or taste.

  3. Chinese modernization has goals, plans and strategies, and will certainly be realized.

  General Secretary of the Supreme Leader pointed out: "Comrade Mao Zedong led the people to create an advanced socialist system. Only socialism can save China and develop China. " Building a socialist modern power and realizing the great rejuvenation of the Chinese nation is the grand goal that our party has been striving for for for more than 100 years. From the first five-year plan to the fourteenth five-year plan, the consistent theme is to build China into a socialist modern country. With profound thinking and forward-looking vision, Comrade Mao Zedong made unremitting exploration on how to realize a powerful socialist modernization country, and made indelible historical contributions to the foundation and successful expansion of China’s socialist modernization. On the construction goal, Comrade Mao Zedong pointed out: "Our people should have a grand plan, and strive to change our backward situation in economy, science and culture within a few decades, and quickly reach the advanced level in the world", and pointed out that the goal of the Communist Party of China (CPC) people "lies in building a new society and country of the Chinese nation". The task of the working class in China is not only to fight for the establishment of a new-democratic country, but also to fight for the industrialization and agricultural modernization of China and make China. In terms of construction planning, Comrade Mao Zedong led the formulation of a two-step planning arrangement for the "four modernizations", that is, the first step,Establish an independent and relatively complete industrial system and national economic system; The second step is to fully realize the modernization of agriculture, industry, national defense and science and technology. In terms of development strategy, Comrade Mao Zedong emphasized that China’s socialist modernization can only take its own road and cannot mechanically copy foreign experience; Starting from the basic national condition that China is a big agricultural country, we should correctly handle the relationship between heavy industry, agriculture and light industry on the basis of agriculture and embark on an industrialization road suitable for China’s national conditions. It is necessary to mobilize all positive factors and unite the people of all ethnic groups throughout the country to build a powerful socialist country; It is necessary to grasp the basic contradictions in socialist society and pay attention to adjusting the situation that productivity is incompatible with production relations and economic base is incompatible with superstructure; We must properly handle the ten major relations in socialist construction and the relationship between accumulation and consumption; Take a peaceful approach, adhere to an independent foreign policy of peace and adhere to the Five Principles of Peaceful Coexistence. These forward-looking thinking and strategic exploration have accumulated practical experience and ideological wisdom for China’s socialist modernization.

  General Secretary of the Supreme Leader pointed out that Chinese-style modernization is based on China’s reality, conforms to China’s national conditions, has goals, plans and strategies, and we will make solid progress step by step. A series of important expositions published by the Supreme Leader General Secretary around Chinese modernization are lofty in conception, rich in connotation and profound in thought. It is of great significance to further deepen the understanding of the connotation and essence of Chinese modernization, summarize the China characteristics, essential requirements and major principles of Chinese modernization, and initially construct the theoretical system of Chinese modernization, so as to make Chinese modernization clearer, more scientific and more feasible, and to comprehensively promote the construction of a strong country and the great cause of national rejuvenation with Chinese modernization in the new era and new journey. To realize the great rejuvenation of the Chinese nation with Chinese modernization, we must persist in developing in inheritance and innovating in keeping the right. We should not only learn from Comrade Mao Zedong’s thought of "overall consideration" in socialist modernization, but also ensure the continuous improvement of people’s material and cultural living standards. We should also combine our party’s theoretical innovation and practical creation in the new era to safeguard the foundation, source, root and soul of Chinese modernization. Unswervingly adhere to the China characteristics, essential requirements and major principles of Chinese modernization, deeply explore and answer new topics encountered in practice, open up a new realm of Marxism in China, deepen the understanding of the laws of Chinese modernization, and better promote the great cause of Chinese modernization.

  4. Open a new world of career development through tenacious struggle

  General Secretary of the Supreme Leader pointed out: "More than 100 years ago, Comrade Mao Zedong said: ‘ We always have to work hard! We always have to push forward desperately! Our golden world, the glorious world, is just ahead! ’” Dare to struggle and dare to win is a powerful spiritual force for the Communist Party of China (CPC) to achieve great cause, and it is also a valuable spiritual character that Comrade Mao Zedong has always advocated and practiced all his life. Comrade Mao Zedong viewed the great struggle from a philosophical perspective, emphasizing that contradictions exist and run through the development of things all the time, which is the alternate unity of old and new processes, and the birth and development of new undertakings can only be achieved through struggle. Faced with the history of national humiliation, people’s suffering and civilization, the Communist Party of China (CPC) people, with Comrade Mao Zedong as the main representative, led the people of China in an arduous revolutionary struggle with great fighting spirit, overthrew the three mountains that weighed on the people of China, and realized the national independence and people’s liberation that the people of China dreamed of in modern times. In the historical process of promoting socialist revolution and construction, the people of the Communist Party of China (CPC), with Comrade Mao Zedong as the main representative, persisted in building socialism independently, did not fear the threats of imperialism and hegemonism and challenges from all sides, firmly safeguarded the territorial integrity and national sovereignty of socialist China, and laid a good foundation for the successful promotion of socialist modernization with the great struggle spirit of opening roads on every mountain and bridging bridges when encountering water.

  Our party relies on struggle to create history, but also depends on struggle to win the future. In the new journey of comprehensively promoting the great rejuvenation of the Chinese nation with Chinese modernization, we must inherit and carry forward the great spirit of independence, courage to struggle, courage to win, unbelief in evil, fear of ghosts and oppression, which Comrade Mao Zedong has always advocated, under the strong leadership of the CPC Central Committee with the Supreme Leader as the core. Take the initiative to fight, dare to struggle, seize the day and fight tenaciously, put the development of the country and the nation on the basis of their own strength, firmly hold the destiny of national development and progress in their own hands, overcome all kinds of difficulties and challenges on the road ahead, and March forward courageously along the road of Socialism with Chinese characteristics in order to comprehensively promote the construction of a strong country and the great cause of national rejuvenation with Chinese modernization.

  (Author: Qi Yiping Tang Junfeng, a researcher at the New Era Socialism with Chinese characteristics Thought Research Center, the supreme leader of the National Defense University)

Changsha Mercedes-Benz GLS price reduction news! The maximum profit is 256,000, and the car is sufficient.

In [car home Changsha Preferential Promotion Channel], preferential activities are being carried out, with the highest preferential amount reaching 256,000 yuan and the lowest starting price of 804,000 yuan. If you want to know more preferential information, please click "Check the car price" in the quotation form to get a higher discount.

长沙奔驰GLS降价消息!最高让利25.6万,现车充足

The design of Mercedes-Benz GLS shows the perfect combination of luxury and strength. The front part of the car adopts Mercedes-Benz family front face design, and the large-size air intake grille with exquisite chrome decoration shows the unique charm of Mercedes-Benz brand. The body lines are smooth, and the tough body outline gives GLS a domineering temperament. On the whole, Mercedes-Benz GLS has found a perfect balance between luxury and sportiness, and has become a rare luxury SUV.

长沙奔驰GLS降价消息!最高让利25.6万,现车充足

With its body size of 5210*2030*1823mm and wheelbase of 3135mm, Mercedes-Benz GLS shows a broad and atmospheric appearance. The side lines of the car body are smooth and tough, which shows its luxury and strength. The tires equipped with 275/50 R20 and distinctive rim style enhance the overall sense of movement and luxury atmosphere.

长沙奔驰GLS降价消息!最高让利25.6万,现车充足

The interior of Mercedes-Benz GLS adopts a luxurious and exquisite design style, and the spacious cockpit provides a comfortable space for passengers. The steering wheel is made of leather, which supports electric up and down and forward and backward adjustment, which increases the convenience of driving. The 12.3-inch central control screen is equipped with intelligent voice recognition control system, which can recognize the instructions of multimedia system, navigation, telephone, air conditioner, skylight and window, and improve the convenience and sense of technology of driving. Type-C interface and USB/Type-C interface are also provided under the center console, which is convenient for passengers to charge the equipment. The seat is made of imitation leather. The main and co-pilot seats have the functions of heating, front and rear adjustment, backrest adjustment, height adjustment (4-way), leg rest adjustment and lumbar support (4-way), and also support electric seat memory to ensure the comfort of riding. The second row of seats also supports front-back adjustment and backrest adjustment, and the rear seats can be laid down in proportion, which increases the flexibility of storage space.

长沙奔驰GLS降价消息!最高让利25.6万,现车充足

Mercedes-Benz GLS is equipped with a 3.0T turbocharged engine with 380 horsepower, with a maximum power of 280kW and a maximum torque of 500 N m.. With the 9-speed automatic manual transmission, it provides a smooth and efficient driving experience.

Car home car owners have their own opinions on the fuel consumption performance of Mercedes-Benz GLS: "Don’t save that oil money at this price. After all, the size of the power itself is here. In fact, the fuel consumption is generally around 12 for high speed, and you should be prepared for 15 for urban areas. Although the fuel consumption is not low, considering the level and positioning of the car, I think it is acceptable. After all, if you buy this car, you are not trying to save fuel at all, are you? "

FAW Toyota Crown Land Display: Cost-effective, large space, practical first choice

FAW Toyota, an amazing car.

In terms of price, it is highly competitive, allowing you to own a high-quality SUV without having to pay a high price.

Crown land put luxury two-wheel drive version, the price is only 259,800 yuan, cost-effective.

As a true seven-seater SUV, the Crown Land Display’s spatial performance is even more impressive.

The new Toyota Land is like a reliable partner.

It has a spacious space, like a moving castle, capable of accommodating the trivial and beautiful aspects of life.

Whether it is the daily commute items or the family’s luggage, it can be easily accommodated.

When traveling with the whole family, everyone can find a comfortable spot and never feel tired during a long journey.

The trunk is spacious and can accommodate a large number of luggage and items, providing great convenience for your travel.

Its appearance is atmospheric and stable, showing noble temperament. Strong power and stable handling performance make long-distance travel easy and enjoyable.

The Crown Land Display is equipped with Toyota’s smart electric hybrid dual engine. Not only is it powerful, it responds quickly when starting and accelerating, but also achieves excellent fuel economy.

Whether it is urban roads or outdoor exploration, Crown Land Release can be used with ease.

Crown Land uses space to carry life, chases distance with strength, and accompanies you to start a wonderful life journey.

2022 Mercedes-Benz GLE450 king breath domineering return

  The sides of the 20 450 car bodies are more finely crafted than the 19 models. The top or waist line and tailgate design are very smooth and natural. The rear privacy glass can well protect the privacy of the rear row. The window lines, the design of the front and rear light sets are more focused, the round lines, the 20-inch AMG sports wheels and the overall design of the body are very sporty, and the overall design looks like it is a smaller version.

  The distinctive feature of the 20 GLE450 is that there is a sloping or vertical tailgate at the rear. After opening the door, the luggage compartment space is connected to the passenger space. The rear bumper is wrapped in matte aluminum alloy, which makes it full of texture and wildness. In business situations, it shows domineering, and for family members, this car brings complete security.

  The new generation of Mercedes-Benz GLE450 uses the family design language, which has changed a lot compared to the tough shape of the old model. For the first time, the model provides both off-road and sports appearance kits. The hexagonal large mouth air intake grille has become flatter, and the interior adopts a Mercedes-Benz gypsy dot matrix layout, with thick chrome trim, and a huge three-pronged star logo, which brings a strong visual impact.

  It is very important for the 20 Mercedes-Benz GLE450 to adhere to the classic feelings, and it is also very important to make a big change. Many people around me have chosen other models because of the old GLE’s old and tired interior, so this replacement interior change is imminent. Compared with the old model, the new generation GLE car has changed very thoroughly. The addition of dual screens and the trend of central four air conditioners has brought more technological atmosphere in the car in addition to the usual luxury. The wrapping center console strikes a good balance between sports and luxury. The center console is wrapped in high-end soft materials, and there is also a stitching process and a large area of wood grain veneer to embellish.

  The interior atmosphere of the 20 Mercedes-Benz GLE450 is more luxurious, and the relatively simple function button design also makes the operation more concise. The steering wheel of the new car centralizes the control of the stereo, phone and driving computer. The overall vision of the Mercedes-Benz GLE450 is consistent with the interior style of the center console, bringing endless luxury to drivers and passengers, and also highlighting the high-end atmospheric style and luxurious beauty of Mercedes-Benz.

  20 Mercedes-Benz GLE450 models are equipped with a 3.0TV6 turbocharged engine, with a maximum power of 367 horsepower, a maximum torque speed of 500, and a maximum power of 270. In terms of maximum power speed 5000-6000 transmission, GLE will be fully replaced with Mercedes-Benz’s latest 9AT automatic transmission. Rich driver assistance systems and high-tech configurations, night vision systems, blind spot monitoring, automatic heating wiper systems, pedestrian detection braking systems, and anti-collision driving assistance systems are all on the scene.

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