Group photo of guests

People’s Daily Online, Beijing, March 19 (Wang Xiaohua) This year’s government work report puts forward that "people-centered development ideas should be adhered to, and efforts should be made to safeguard and improve people’s livelihood, and the people’s sense of gain has been continuously enhanced." Since the first three-year "Action Plan for Further Improving Medical Services" was officially launched in 2015, hospitals at all levels have made positive achievements in innovating service measures and improving people’s medical experience in view of the "bottleneck" problem of medical treatment. With the launch of the new round of improving medical service plan, how to make "seeing a doctor more comfortable, providing more considerate services and increasing people’s sense of obtaining medical treatment"?

During the two sessions of the National People’s Congress in 2018, People’s Daily Online and People’s Health jointly organized a series of roundtable forums on "Healthy Chinese". In the special session of "Further Improving Medical Services" held on March 15th, five guests from government agencies and medical institutions gathered at People’s Daily Online to discuss the beneficial measures of "Further Improving Medical Services".

Innovating medical service mode and improving patients’ accessibility to medical treatment

Jiao Yahui, deputy director of the Medical Administration and Hospital Authority of the National Health and Family Planning Commission, said that after the expiration of the first three-year "Medical Service Improvement Plan", patients’ access and satisfaction were improved through the extensive application of information technology, improvement of service quality, acceleration of sinking of resources and continuous improvement of medical services.

Jiao Yahui introduced that since China launched the first three-year "Action Plan for Further Improving Medical Services" in 2015, the service process has been optimized by means of Internet informationization, which has alleviated the long-standing problem of "three long and one short" (long waiting time for medical treatment, long payment time, long time for taking medicine and short time for seeing a doctor). Through the innovative service model, the number of patients going to and from the hospital, repeated queuing in the hospital, the whole waiting time for outpatient service and the average length of stay were effectively reduced.

According to the data of 5.87 million valid questionnaires of real-time online satisfaction survey, the overall satisfaction of outpatients and inpatients in tertiary hospitals in China reached 90.7 points and 93.9 points; The analysis of 28.83 million pieces of information related to medical services on the Internet shows that netizens’ overall feelings about medical services are positive, which fully reflects the positive results achieved in improving medical services in the past three years.

Building emergency specialist alliance and opening up the "green channel" for emergency patients

Li Weimin, deputy to the National People’s Congress and president of west china hospital, said that this year, Huaxi Hospital will focus on optimizing the medical treatment mode and improving the satisfaction of emergency patients. At the same time, through the construction of emergency specialist alliance, the information triage before emergency admission can be realized, and the rescue and treatment resources can be dispatched in time, so as to truly open a green channel for emergency patients to check and be admitted to hospital.

Li Weimin introduced that since the establishment of the telemedicine network in West China Hospital in 2001, more than 640 hospitals in 20 provinces and cities across the country have joined the telemedicine network, providing telemedicine education and multidisciplinary joint consultation for difficult cases in remote areas and ethnic minority areas, which not only enables grassroots patients to get timely diagnosis and quality treatment programs, but also improves the local medical service level.

Take effective measures to promote the appointment and medical association system

Feng Guosheng, chairman of Beijing Chaoyang Hospital affiliated to Capital Medical University, introduced the effective measures taken by Beijing Chaoyang Hospital in improving medical services in recent years. He pointed out that in terms of appointment diagnosis and treatment, since 2012, Chaoyang Hospital has adopted various forms to carry out appointment registration services to facilitate patients to see a doctor. In the process of diagnosis and treatment, the appointment time, including the examination time, is accurate to 15 minutes, which greatly reduces the waiting time of patients in the hospital and obviously improves the medical environment.

In terms of vigorously developing the construction of medical associations, in 2012, Chaoyang Hospital established a medical association with Chaoyang Hospital as the core and secondary hospitals and community medical centers as participants under the guidance of the government. Through the standardized operation within the medical association, more patients with common diseases and chronic diseases can enjoy the high-quality medical resources of large hospitals at their doorsteps.

Feng Guosheng said that Chaoyang Hospital has also realized telemedicine through information technology, and further strengthened the innovation of outpatient services, such as setting up symptom clinics and special disease clinics to facilitate patients to seek medical treatment.

Extend the service to the grassroots level and let more children enjoy health.

Ni Xin, dean of Beijing Children’s Hospital affiliated to Capital Medical University, pointed out that Beijing Children’s Hospital has implemented a comprehensive appointment system for non-emergency patients since June 2015. Through a variety of ways, patients are guided and facilitated to make appointments and time-sharing visits, so that the waiting time of patients is shortened, the peak flow of outpatients is reduced, and the medical experience is significantly improved. These methods mainly include: dynamically adjusting staff and improving service space; Implement centralized appointment for large-scale examinations to reduce patients’ running back and forth; Increase voluntary service and improve the online and offline guidance system; Open professional outpatient service and expert team outpatient service to make the process of treating intractable diseases more convenient.

Ni Xin introduced that in order to facilitate children to seek medical treatment nearby, Beijing Children’s Hospital and Children’s Research Institute took the lead to promote the common development of pediatrics in 16 municipal general hospitals in Beijing. By hosting three children’s hospitals, the medical level of local hospitals has been further improved. Beijing Children’s Hospital and 23 provincial children’s hospitals across the country set up a cross-provincial specialist alliance to achieve the goal of "doctors move and patients don’t move". In the next step, we will use artificial intelligence to comprehensively improve the level of medical services, extend services to the grassroots, increase support for poor areas, and let more children enjoy health.

Carry out the comprehensive upgrade of information system for the construction of smart hospitals

Jiang Lihong, deputy to the National People’s Congress and president of the First People’s Hospital of Yunnan Province, said that in the past three years, the First People’s Hospital of Yunnan Province has actively implemented the improvement of medical services, mainly focusing on two themes, and has achieved certain results: First, the construction of smart hospitals. The hospital information system has been upgraded in an all-round way, and the people’s appointment registration rate has increased from about 30% to more than 91% after the new system goes online. The hospital implemented the one-card service, and invested in the construction of 126 self-service machines. Patients can register for ID cards or medical insurance cards.

The second is the construction of medical association and graded diagnosis and treatment. People in Yunnan Province, especially in mountainous areas, live in scattered areas, and fewer patients in Yunnan Province are transferred to other provinces for medical treatment. The demand for medical associations and graded diagnosis and treatment is more urgent. The First People’s Hospital of Yunnan Province and 215 state (city) and county hospitals in the province formed a medical association, and 3-5 specialists were selected from 33 state-level hospitals to form a specialist alliance. At the same time, 6 provincial-level expert grass-roots workstations and 66 secondary hospitals and community expert teams were set up to build a "joint laboratory for precision medicine and eugenics" with the hospitals in the medical association, forming a multi-level assistance mechanism such as hospitals, specialist alliances and expert teams.

?　　Foreword　　

In 1993, Belgian scientists discovered a new antibody-nano-antibody (VHHs) in camel serum, which is different from the traditional antibody structure and only consists of heavy chain variable regions. Compared with traditional antibodies, nano-antibodies have the advantages of stable physical and chemical properties, low immunogenicity, strong tissue permeability, and can recognize epitopes that traditional antibodies cannot recognize, which makes them a strong and beneficial supplement to traditional antibodies.

Nano-antibody is only composed of heavy chain variable region, with small molecular weight and simple structure, which enables it to realize stable expression in various expression systems. So far, VHHs has been expressed in many expression systems, from prokaryotic cells, yeast, fungi, insect cells, mammalian cell lines to plants. This paper mainly introduces the expression of nano-antibody in different expression systems, and the present situation and development trend in the field of this system.

Prokaryotic expression system　Prokaryotic expression system is the earliest mature protein expression system studied. Obtaining foreign proteins through prokaryotes can obtain gene expression products in a short time, and the cost required is relatively low. The expression system mainly includes Escherichia coli expression, Bacillus subtilis expression and Streptomyces expression. Among them, Escherichia coli system is the most widely used, and the prokaryotic system generally refers to the expression of Escherichia coli.

Escherichia coli expression system　Escherichia coli expression system is the most important expression platform of recombinant protein in laboratory environment, and the expression is controlled by lactose operon. The host of Escherichia coli system has the advantages of fast growth, simple culture, low price, clear genetic background and high protein expression. However, it can not modify the expression product after translation, and the expression product contains a lot of endotoxin and is easy to form inclusion bodies.

Common host bacteria of Escherichia coli expression system

Periplasmic space, as the only compartment with oxidation environment in Escherichia coli, is the most commonly used expression system of nano-antibodies containing specific disulfide bonds. In addition to aerobic environment, there are many partners and isomerases in the periplasmic space, which can promote the correct formation of disulfide bonds and help protein fold. Nano-antibody protein is first produced in the cytoplasmic space, and then secreted into the periplasmic space through Sec pathway, SPR pathway or Tat pathway. After signal peptide is removed by signal peptidase, the target protein can be obtained [1].

Up to now, many VHHs have been successfully expressed in periplasm, some of which can reach tens of milligrams per liter, but there are still a lot of VHHs with low yield. This is because many fusion proteins can not be effectively secreted in the periplasmic space, and cytoplasmic expression seems to be the only expression mode of such fusion proteins [8].

The cytoplasm is a reduced compartment, so that the proteins expressed through the cytoplasm can not be folded correctly, and most of them are inclusion body proteins. The proteins are protected from the degradation of intracellular enzymes and are easy to be separated in high purity and concentration. However, there are many kinds of proteins in cytoplasm, and it is difficult to purify them. At the same time, nonfunctional inclusion proteins need to be completely denatured and refolded to be recovered from these inclusions, but the recovery of VHHs is usually inefficient [1]. In order to solve the problem of cytoplasmic expression, Xue X and others designed a new dialysis-dilution device in 2016. Using this device, researchers refolded VHHs and achieved a recovery rate of 85%, while the conventional dialysis and dilution methods only reached 13%[9]. Bacterial cytoplasm can be an effective compartment to produce correctly folded nanoparticles when expressed by recombinant vectors with sulfhydryl oxidase and disulfide isomerase activities. Larger volume and wider cytoplasm of chaperone/folding enzyme can achieve high yield of nano-antibody [6]. At the same time, double mutants with defects in thioredoxin and glutathione pathways have been developed. Some of these strains have been sold commercially in recent years, such as Origami (Novagen), Rosetta-gami (Novagen) and SHuffle?T7 (New England Biolabs) [10]. Among them, Shufflet 7 overexpresses a critical periplasmic isomerase DsbC, which can effectively catalyze the isomerization of disulfide bonds. Some studies have found that,The activity of isomerase DsbC can increase the yield of functional recombinant protein in periplasmic research [11].　　

Kavousipour Soudabeh and other modified vectors added four different signal peptide sequences to guide the secretion and expression of nano-antibodies, and found that TrBC signal peptide had the best effect [5]. Jianli Yu et al. used repetitive amino acid sequence motifs (GAGAGS) found in silk fibroin (SFP) as a new fusion tag (SF-tag) to enhance the expression of nanosomes in E.coli.. The transcription level of labeled protein is 2.3-7.0 times that of unlabeled protein, and the yield is increased by 2.5-7.1 times [27]. Xi Xie and others tried to select antifreeze protein AXX, and obtained its reverse transcription protein XXA by synthesizing XXA gene, which was used to develop new soluble fusion tags. It was found that the solubility ratio of fusion protein expressed by XXA fusion tag reached 86%, which was much higher than that of other tags [12].

Other prokaryotic expression systems　Lactic acid bacteria are the most common intestinal probiotics, which are generally considered to be harmless to human body and are very suitable for the production host of therapeutic molecules. However, the existing expression data show that the yield of VHHS produced by lactic acid bacteria is low, about 1-3mg/L, which is much lower than that of Escherichia coli [13,14]. Lactobacillus rhamnosus DSM14870, as a normal flora in human vagina, can express HIV antibody in the form of soluble or cell wall anchor fixation, and is a suitable expression host for HIV antibody [2]. When Bacillus brevis choshinensis was used for 3L fed-batch fermentation, the yield was as high as 3g/L[15]. This system is easy to manipulate genes, has no endotoxin and shows weak protease activity, so it is a very noteworthy system.

Eukaryotic expression system　

Due to the defects of prokaryotic expression system, such as difficult purification of inclusion body protein and incomplete protein modification, people began to use eukaryotic expression system to study genes. At present, eukaryotic expression systems commonly used in genetic engineering research include yeast expression system, insect cell expression system and mammalian cell expression system.

Yeast expression system　Yeast system has clear genetic background, simple operation, easy genetic operation, perfect eukaryotic protein expression control system and advantages of both prokaryotic and eukaryotic expression systems. Yeast eukaryotic protein expression systems include methanol yeast expression system, Saccharomyces cerevisiae expression system, Schizosaccharomyces expression system and Kluyveromyces expression system [17].

Saccharomyces cerevisiae is the first yeast fermented by human beings, which has no specific virus and low cost. At present, it is the largest yeast expression system in shake flask culture, with the output exceeding 100mg/L[16]. Some amino acids in VHHs can participate in the recruitment of molecular chaperones in endoplasmic reticulum, thus narrowing the difference of molecular chaperones between Saccharomyces cerevisiae and mammalian cells, which is beneficial to the folding kinetics of nano-antibodies and improving the yield of nano-antibodies in Saccharomyces cerevisiae [17]. The protein expressed by Saccharomyces cerevisiae is prone to hyperglycosylation, and a large number of endogenous proteins are produced during fermentation, so the secretion efficiency of the target protein is low [1]. Considering the above problems, Saccharomyces cerevisiae is gradually replaced by methanol yeast represented by Pichia pastoris.

Pichia pastoris expression system is an efficient expression system of foreign proteins. This microorganism does not accumulate toxic ethanol, but only secretes a few endogenous proteins, and its glycosylation degree is the same as that of mammalian cells, so its immunogenicity is weak, so it is the most commonly used eukaryotic expression system. Pichia pastoris has a strictly regulated methanol inducible AOX1 promoter, which is suitable for high expression of foreign proteins [1]. But methanol is a highly toxic and dangerous chemical product. The GAP promoter without methanol induction is used instead of AXOI, and the carbon source does not need to be changed during the culture process, so the operation is simpler and the time for foreign proteins to reach the peak level can be shortened. The yield and affinity of nanoparticles produced by this system are similar to those produced by methanol-induced expression. It has been studied that the yield of nano-antibody expressed by this system in shake flask is 51.71mg/L[18] and 16mg/L[19].

Fungal expression system　

Some filamentous fungi, such as Trichoderma and Aspergillus, can secrete a large number of foreign proteins in the culture medium. However, the fungal system not only expresses protein of interest, but also produces many proteases, which affects the yield. Joosten et al. obtained only 1.5 mg/L VHHs in Aspergillus awamori medium. After adding 0.25% BSA, it reached 7 mg/L. It is reported that more than 80% of VHH is degraded or adhered to the cell wall compared with endogenous xylanase secreted efficiently in this system, and researchers believe that the low secretion efficiency of VHHs is the bottleneck of fungal expression [20]. In order to overcome this limitation and protect VHHs from degradation, other researchers fused VHH with the high amylase A signal sequence (sTAA) of Rhizopus oryzae lipase (N28) and the N-terminal 28 amino acid fragment (N28), so that the highest yield of VHHs expressed in Aspergillus oryzae reached 73mg/L, which was 300-800 mg/L lower than that of Escherichia coli [21]. The final yield of GlaB-VHH fusion protein in Aspergillus oryzae can reach 610mg/L, which provides the possibility for high expression of nano-antibody, but its stability needs to be verified [22]. In addition, VHH[23] was expressed by maize head smut in unconventional secretion pathway.

Insect cell expression system　

Insect cells are a widely used eukaryotic expression system, and recombinant baculovirus vectors (such as AcMNPV) can specifically transfect insect cells. Its survival in nature is short, and the strong promoter is inactivated in mammals and cannot infect vertebrates, so the recombinant baculovirus is safe for human beings. Proteins with complex structures under the control of strong promoters may not be able to form correct folding and post-translation modification, which may lead to the aggregation of target proteins and reduce antibody production, so the expression yield of VHHs in this system is much higher than that of other types of antibodies [17].

Gómez-Sebastián and others used the improved baculovirus expression system (IBES? technology) to express VHHs for the first time. The chigger larvae were inoculated with different recombinant baculovirus inoculation methods. The yield of VHH extracted from larvae is 257 mg/L, and the recovery rate after purification is 50%[7]. When expressing anti-endothelial cell selection protein, Drosophila cell SC-2 secreted 12-14mg/L, but the target protein was not detected when expressed in Escherichia coli at the same time, which may be related to the processing and modification ability of insect cells [26].

Mammalian cell expression system　Mammalian cells are the best expression system for therapeutic antibodies, because the produced antibodies have the weakest immunogenicity. At present, the main cell lines include CHO, NS0, Sp2/0, HEK293 and per C6 [17]. Among them, CHO cells grow rapidly and adapt to serum-free suspension culture, which is the most popular host. They can express VHHS up to 100mg/L in shake flask [24]. HEK293 cells are more commonly used in the laboratory because of transient transfection and semi-stable expression, because they require less time and labor. However, monoclonal antibodies approved for the treatment of human diseases are only produced by CHO, NS0 and SP2/0. So far, HEK293 cells have not been used to produce VHHs, and there are few reports about producing antibody fragments by this method [17]. In most literatures, CHO is used to produce antibody fragments. Up to now, 50% of the therapeutic proteins produced in industry are still produced by CHO [1]. The production costs associated with mammalian cell lines are much higher than those associated with any other laboratory research platform.

Common host cells of mammalian expression system

Plant expression system　Compared with other expression systems, plant production platform (stable and transient expression system) is cheap, safe, capable of folding and assembling complex proteins and post-translation modification, easy to expand, and unaffected by human pathogens and diseases. It is an ideal protein expression host and is usually used as an alternative method for mammalian expression systems. In addition, plant expression products can be concentrated in specific organs, such as leaves or seeds, and can be taken orally directly. Tobacco leaves are the most common hosts for expressing VHHs, while the proteins expressed in Arabidopsis and rice seeds have attracted much attention because of their direct oral input of VHHs[1]. The stable transformation methods commonly used in plant system expression have some problems, such as the recombinant gene escaping to nature or the time-consuming transformation. Therefore, some studies have proposed the transient expression system of plant virus expression vector as an alternative method, and the nano-body content with correct conformation reaches 0.45% of the total soluble protein [25].

Present situation and development of nano-antibody expression　

Escherichia coli expression system is the most commonly used expression system of nano-antibody, which has two expression modes: periplasmic expression and cytoplasmic expression, each with its own advantages and disadvantages. Some oxidation engineering strains have been modified, but more experimental support is needed. In addition, various methods of modifying vectors, such as adding labels or signal peptides, have been put forward and have been verified by experiments. Compared with Escherichia coli, Pichia pastoris has excessive glycosylation, which may lead to immunogenicity and ultimately affect its clinical application. The expression systems of fungi, insects, plants and mammals are much more complicated than prokaryotic and eukaryotic expression systems, and are generally not easily adopted after considering the production time, cost and laboratory conditions.

Escherichia coli system is fast, convenient and cheap, and it is the first choice for VHH expression under most laboratory conditions. When some types of VHHs can’t be successfully produced in E.coli, other systems will be used instead.

List of nano-antibody expression

The number of diabetic patients in the world continues to grow. Relevant data show that there is one diabetic in every eight adults in China and one pre-diabetic in every two adults in China.

Diabetes is not terrible, but its complications, such as cardiovascular and cerebrovascular diseases, renal failure, diabetic foot and retinopathy … These chronic complications have gradually become the main cause of death for diabetics.

Dangerous chronic complications of diabetes mellitus

Diabetes is a group of lifelong metabolic diseases caused by multiple causes and characterized by chronic hyperglycemia. The key to lowering the blood sugar level in the body is insulin, which helps glucose from food to enter cells from the blood to generate energy. When insulin is not well produced or utilized, the blood glucose level will rise, and when it rises to a certain extent, diabetes will occur.

Elevated blood sugar is not the end point of diabetes. Long-term high blood sugar damages the body, causing pathological changes in various important organs of the human body. With the extension of the course of disease and poor blood sugar control, diabetic patients will gradually develop chronic complications. Complications will have serious consequences in the later stage, such as blindness, renal failure, myocardial infarction, heart failure, stroke and amputation, which will seriously affect the quality of life of patients.

Chronic complications of diabetes are generally divided into macrovascular complications, microvascular complications, neuropathy and diabetic foot.

I. Cardiovascular diseases

Atherosclerosis is one of the main causes of cardiovascular diseases, and insulin resistance and hyperglycemia are the main factors leading to cardiovascular complications in diabetic patients. Studies have shown that diabetic patients have an increased risk of heart failure and/or cardiac dysfunction, and long-term hyperglycemia can also lead to various cardiac dysfunction, including arrhythmia and sudden cardiac death.

1. Symptoms and manifestations

There may be no symptoms in the early stage, and with the progress of the disease, discomfort symptoms such as chest pain, chest tightness, palpitation, shortness of breath and arrhythmia may appear after work. Some patients may have no obvious pain even when myocardial infarction occurs because of the influence of hyperglycemia on cardiac autonomic nerves.

2. How to screen

For diabetic patients, ECG and echocardiography should be performed at the time of diagnosis, and at least once every six months.

Hyperglycemia increases the risk of stroke. A comprehensive analysis of 102 prospective studies found that compared with non-diabetic patients, the risk of ischemic stroke increased by 2.3 times and the risk of hemorrhagic stroke increased by 1.6 times. This correlation is not only related to the incidence of cerebrovascular disease, but also related to the prognosis and functional status of the disease.

Second, cerebrovascular diseases

1. Symptoms and manifestations

If diabetic patients have symptoms such as dizziness, black eyes or blurred vision, slurred speech, numbness and weakness of one limb, they should be on high alert for possible cerebrovascular diseases and seek medical advice in time.

2. How to screen

If diabetic patients have danger signs of stroke, they should immediately have brain CT or magnetic resonance (MRI) and other related examinations.

Third, kidney disease

Diabetic nephropathy is a common microvascular complication of diabetes, which affects about 25% of diabetic patients. It has become the main cause of chronic kidney disease and end-stage renal disease.

1. Symptoms and manifestations

There are usually no obvious symptoms in the early stage, and some patients may have increased urine foam, renal function damage, hypertension and edema. When the disease develops to the advanced stage, severe renal failure and uremia may occur, and dialysis treatment is needed.

2. How to screen

Generally speaking, patients with type 2 diabetes have a urine test every six months to one year to detect the content of microalbumin. If the index rises abnormally, it is recommended to seek medical examination.

Fourth, retinopathy

Diabetic retinopathy is one of the common complications of diabetes and one of the main causes of blindness.

1. Symptoms and manifestations

There may be no symptoms in the early stage, but with the progress of the disease, symptoms such as blurred vision, visual field defect, decreased vision at night, and floaters may appear. In the late stage, it may develop into serious situations such as retinal hemorrhage and retinal detachment.

2. How to screen

It is recommended that diabetic patients have an annual fundus examination, including optometry, intraocular pressure measurement and fundus examination. Fundus examination can observe the retina by dilating the pupil.

V. Neuropathy

Diabetic neuropathy refers to the damage of diabetes to the nervous system, including the involvement of peripheral nerves and autonomic nerves.

1. Symptoms and manifestations

Common symptoms include paresthesia (such as pain, tingling and numbness), impaired motor function, digestive system problems (such as delayed gastric emptying and constipation) and sexual dysfunction.

2. How to screen

Diabetic patients should have regular nervous system examination, including foot examination, electrophysiological examination and autonomic nervous function test.

6. Diabetic foot

Diabetic foot is one of the serious and costly chronic complications of diabetes, which can lead to amputation and death. In China, the incidence of new foot ulcers in diabetic patients over 50 years old is 8.1% within one year, and the incidence of new foot ulcers in cured diabetic patients is 31.6% within one year.

1. Symptoms and manifestations

In the early stage, numbness and abnormal temperature sensation of the foot may occur, and then redness and skin breakage may occur, which will gradually increase.

2. How to screen

All diabetic patients should have their feet examined regularly.

Check the foot skin for abnormal cyanosis and ulceration;

Check whether the pain, temperature and touch of extremities are normal;

Check whether the pulsation of dorsal foot artery and posterior tibial artery is weakened;

If you suspect vascular diseases, you can check the vascular ultrasound of lower limbs.

"Misunderstanding" of Diabetes

The complications of diabetes are closely related to the degree of blood sugar control. Only by paying attention to the changes of blood sugar can we prevent and control the acute and chronic complications of diabetes. In this regard, there are some misunderstandings that need special attention.

1. Is there no problem without symptoms?

Answer: Wrong!

Many patients often neglect the treatment and management of diabetes in the early stage of diabetes because the symptoms are not obvious, which leads to long-term substandard blood sugar and poor control, which further affects all systems of the whole body and increases the risk of complications.

Once you are diagnosed with diabetes, whether you have symptoms or not, you should insist on regular, scientific and reasonable treatment. Only in this way can we effectively control blood sugar and reduce complications.

Experts remind that the severity of diabetes can not be judged only by the severity of symptoms.

2. Can I stop hypoglycemic drugs without authorization?

Answer: Wrong!

Diabetes is a lifelong disease, and it can’t be cured at present. Just because the symptoms disappear and the blood sugar drops to normal after regular treatment does not mean that the diabetes has been cured, and the drug treatment can be stopped immediately.

The vast majority of patients still need to continue to receive medication after their condition is stable. If the drug is stopped at will, the blood sugar will fluctuate. At this time, the original dosage may not achieve the ideal hypoglycemic effect, and it may be necessary to increase the dosage or even use a variety of hypoglycemic drugs in combination, which will also cause certain damage to the body.

Experts remind: strictly following the doctor’s instructions for drug treatment is the key to control blood sugar and reduce complications.

3. If the blood sugar control is normal, can you relax your diet management?

Answer: Wrong!

In the treatment of diabetes, diet management is very important, which is called one of the "five carriages" of diabetes treatment. Others include exercise, medicine, blood sugar monitoring and self-management education. Failure to control diet is likely to lead to large fluctuations in blood sugar, which is not conducive to maintaining a stable metabolic state and weight.

Experts remind that diet management should run through the whole process of diabetes treatment, so don’t let your guard down just because the blood sugar results are normal, so as to avoid serious consequences due to the unpredictable risk factors such as inaccurate blood sugar monitoring results and drug taboos.

Do all diabetics have complications?

Not all diabetics will have complications.

At present, in clinic, there are many patients whose blood sugar, blood lipid, blood pressure and other indicators have reached the standard, and the course of disease is as long as 30-40 years. It can be seen that diabetic patients should pay attention to the control of blood sugar and cannot ignore the condition.

At the same time, we should follow the doctor’s instructions for drug treatment, and we should not stop taking drugs at will. Diet management is also very important in the treatment of diabetes, even if blood sugar control is normal, diet management can not be relaxed. In addition, not all diabetic patients will have complications, and following the standard treatment can reduce the risk of complications.

1. Control blood sugar, blood pressure and blood lipid.

Achieving the standard of blood sugar is the key to prevent complications in diabetic patients. The general ideal targets are: fasting blood glucose 4.4 ~ 7 mmol/L, postprandial blood glucose ≤10mmol/L, glycosylated hemoglobin (HbA1c)<7.0%, depending on the patient’s age and complications.

Even for patients with well-controlled blood sugar, blood sugar should be monitored 2 ~ 4 times a week. For patients with high blood sugar fluctuation or high blood sugar, blood sugar should be monitored 7 times a day, and treatment should be adjusted in time.

The control of blood pressure and blood lipid plays an important role in reducing the complications of diabetes and the risk of heart disease. Blood pressure should be monitored every time you visit a doctor, and blood lipid and electrocardiogram should be checked at least once a year.

Step 2 change your lifestyle

Reasonable diet, low fat and less oil, small amount of meals, regular quantitative meals. Quit smoking and limit alcohol, exercise properly, work and rest regularly, and control weight.

Step 3 check regularly

Diabetic patients should go to the hospital regularly for relevant examinations, which is not only beneficial to blood sugar control, but also can actively prevent complications and strive for early detection and early treatment. Screening mainly includes blood biochemical examination, glycosylated hemoglobin, urine routine, microalbuminuria, electrocardiogram, fundus examination, neuropathy screening, vascular B-ultrasound, etc., so as to achieve early detection and early treatment.

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The National Bureau of Statistics conducts real-time management of statistical investigation projects of various government departments, and has set up a column of "Examination and Approval of Departmental Investigation Projects" on the website of the National Bureau of Statistics for public inquiry.

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Catalogue of statistical investigation items of government departments

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Postal industry statistical investigation system

Topic: picture channel

　　Mariah Carey, 38, and Nick Cannon, 27.

　　Sohu Entertainment News On April 30th, 38-year-old Maria Kelly and 27-year-old Nick Cannon entered the wedding hall. Mariah Carey’s last marriage was 15 years ago, in 1993, when she married Tommy Mottola, a record company executive, and the marriage lasted for five years. The lightning marriage with my little boyfriend who is 11 years younger than me is really surprising. I sincerely hope they can have a happy marriage. Although "sister-in-law love" is a very common thing at present, it is always more attractive in the entertainment industry. Here, let’s take a look at several famous pairs of "sister-in-law love" in Hollywood:

　　Jennifer Aniston (39) and John Meyer (30)

　　

　　Jennifer Aniston and John Meyer

　　Not long ago, they were photographed touching each other by the pool. According to an insider, John Mayer flew to the crew of Jennifer Aniston’s new film Marley & Me, and they spent five sweet days together. The insider said that the two had been in contact with each other by email before. "Aniston really likes John, and the age gap of 9 years old is not an obstacle. For her, this sister-in-law relationship is obviously not a joke. "

　　Kim Cattrall(50) and Alan Wyse (28)

　　

　　Kim-Cattrall-&-Alan-Wyse

　　"Of course I care about the other person’s age, otherwise he is too young to get a driver’s license, and I don’t want to pick him up by car!" Kim Cattrall, the actor of Samantha in Sex and the City, joked that her boyfriend is 22 years younger than her and is a chef.

　　Madonna (49) and Guy Ritchie (39)

　　

　　Madonna and Geric.

　　"Guy always makes me laugh." Madonna said: "He is very talented and smart. Yes, he is ten years younger than me, but I think we are equal. It is difficult to detect the age gap between us."

　　Demi Moore (45) and Ashton Kucher (30)

　　

　　Demi Moore and Ashton Kucher.

　　"Age has never been a problem for me, but it is a big problem in many parts of the world." Demi Moore said that her ex-husband was a famous actor Bruce Willi. Now her married life with Ashton Kucher is very happy, and Ashton Kucher and Demi Moore get along well with their three daughters born by their ex-husbands.

　　Harry Berry (41) and Gabriel Aubry(32)

　　

　　6 Harry Berry and -Gabriel-Aubry

　　The two met while shooting a print advertisement for Versace. On March 16th this year, the crystallization of their love-daughter Nahla Ariela came to the world.

　　Eva Longoria (33) and Tony Parker (25)

　　

　　Eva Longoria and Tony Parker

　　The heroine of Desperate Housewives described her husband, the star player of the Spurs, as a "romantic, considerate and responsible person."

Editor: Liu Lulu

1905 movie network news Recently, a romantic comedy film directed by Li Kelong and starring Xu Shendong, Wang Wei, Liao Weiwei, Quan Rui, Chen Youjun, Gneki and Feng Jiali released a preview and poster, and announced that it will land in the national cinema on November 11th. The film mainly tells the story that Xu Yunfei, an older man, was forced to participate in a "big data love matching experiment" designed by an intelligent marriage company under the pressure of urging marriage. Under the guidance of Xiao Jia, an AI intelligent robot, he constantly met girls with different personalities. In the process of finding the right girl, the trajectory of life has turned a thousand times, and I have passed by the hostess Li Qiuyue constantly, thus staged a journey of finding love under the background of big data.

The film Love Call Waiting focuses on the love in the near future artificial intelligence era, and it is a brand-new urban imagination by director Li Kelong. In recent years, the problem of marriage and love among older young men and women has become a new social pain point, which has also spawned a variety of dating apps and websites. These social platforms for marriage and love mostly use interests, hobbies, personalities and dietary preferences as labels to make a detailed classification of single men and women for young people as a shortcut to find the other half of their lives. Can seemingly highly intelligent technical means really solve the pain point of "empty nesters"? . In the movie, everyone’s hobbies and life trajectories are controlled by a data company, and Xiaojia, a marriage guidance robot, is developed based on big data.

As a love wingman, Xiao Jia, a robot, always accompanies Xu Yunfei, the male host, and makes suggestions for him. In the daily life of "love each other and kill each other", I gradually integrated into the life of the man. With Xiao Jia’s help, many women with different personalities, such as coldness, cuteness and frankness, also came into the man’s life, so many funny scenes were born. For example, according to the instructions of the robot, the man came to the place where "the right girl" was about to appear with plush toys, and he was greeted by a camouflage suit courting man holding flowers. Under the guidance of Xiao Jia, a vicious tongue, the man has repeatedly changed from the excitement of love to the loss of love, constantly accepting the ridicule of fate. At the same time, the film adopts a double-clue narrative structure to show the emotional lines of the man and the woman. After going around, their life trajectories are finally perfectly intertwined.

Can the fate of "lonely life" really be solved by modern technology? The answer may be pessimistic. Big data seems to never grasp the accuracy of love. Perhaps, the code of love depends more on feelings. Fast food, express, express &hellip; &hellip; In today’s era when everything is fast, can love match quickly? The director tried to make an in-depth discussion through the film. Of course, everyone wants to have a sweet love, and also wants to have a love wingman like Xiao Jia to accompany them and guide their love direction. Then you might as well walk into the cinema to appreciate the many possibilities of life. Perhaps, the person who often passes by you, like the hostess Li Qiuyue, is waiting for you in the near future.

The film "Love Call Waiting" re-examines the views on the subject of "love" in the era of big data from the perspective of contemporary urban men and women.

[Pacific Science and Technology News]On November 22nd, the first model of HarmonyOS Zhixingguan Xuanzunjie brand was officially named "Zunjie S800". This model is scheduled to meet the public for the first time at Huawei Mate Brand Festival on November 26th, 2024. According to Yu Chengdong’s disclosure yesterday (November 21st), the length of the first car in Zunjie is about 5.5 meters, which may exceed 99.99% of the cars on the market. It is definitely "heroic atmosphere" and "larger internal space".

Previously, it was reported that the front design of HarmonyOS Zhixing Zunjie S800 adopts the shape of vertical and horizontal stars with crystal headlights, so that the crystal and the headlights are integrated. The Xinghe headlights present a three-dimensional aesthetic feeling at different angles, and the logo is designed with luminous crystal sections.

The body color is designed in purple and silver, and the side door handle is designed in bright stars, which means that the hand can pick the stars, the chrome-plated design is unique, and the pie wheel hub shows luxury temperament. The rear part, the design concept of the Milky Way scroll and the elements of the Rose Nebula make the whole vehicle more recognizable.

In contrast, the Golden Sunflower Guoya ultra-luxury executive sedan sold by FAW Hongqi at the 2024 Guangzhou Auto Show has a length of 5353mm, and the length of Zunjie S800 will exceed this value.

　　For users who often travel with the whole family, they will definitely give priority to seven-seat or large six-seat models, but they often find that the third row of many cars is either too small and impractical, or too expensive. Then, you might as well consider it. It will tell you with facts what is really big six-seat and what is comfortable and equal rights.

　　Yipai eπ 008 is the second model launched after the eπ 007 (sedan). It is positioned as a home intelligent large SUV and has two power forms: pure electric and range extension. The body length is more than 5 meters, the wheelbase is more than 3 meters, and it is a really large six-seat, and the internal space is quite generous. Dongfeng Yipai eπ 008 is expected to sell for between 20-250,000 yuan, and has a quite high quality and price ratio among the same-class models. It is expected to be officially delivered in June.

　　Let’s talk about the size of Dongfeng Yipai e π 008. The length, width and height of the body are: 5002 * 1972 * 1732mm, and the wheelbase is 3025mm. You can buy a large SUV of this size at a price 200,000, which is enough to be exciting. The appearance design of Dongfeng Yipai e π 008 is very atmospheric, and the length of 5 meters is quite impressive from the visual experience.

　　In terms of details, the intelligent starlight grille that supports a variety of welcome rhythm display effects, coupled with the through-through headlights composed of 536 LEDs that echo back and forth, is also full of fashion and technology.

　　From the side, the Yi Pai e π 008 adopts a flat roof design, and the area of the C-pillar small window is also quite large, which brings a longer visual length and also gives more vision to the third row, which does not make people feel depressed. The design of the lower waist line adds a little sense of agility to the side of the body, and at the same time, the chrome decorative strips running through the front and rear enhance more luxury. The Yi Pai e π 008 also uses hidden door handles, which makes the body feel stronger and reduces some wind resistance. The wind resistance coefficient of the whole vehicle is 0.268Cd.

　　The EPI 008 uses 21-inch low-drag wheels, which are matched with Continental low-roll-resistance silent tires, with a tire size of 265/45 R21. These four tires alone are worth a lot of money, and it does not cost money. It does greatly improve the comfort and silence of the whole vehicle.

　　The D-pillar side window is equipped with an LED indicator light to display the battery level when charging.

　　The tail design of the Yi Pai e π 008 is relatively full, and the decorative lines picked on both sides of the bumper add some sports elements. The through tail lights and the characteristic lines of the license plate area create a more three-dimensional sense of hierarchy.

　　The interior of the Yipai eπ 008 is a more composed style and is more durable. With a 15.6-inch central LCD screen and an 8.8-inch LCD instrument panel, the car is equipped with an 8155 chip, and the content displayed on the car interface can be seen.

　　The cockpit leather is made of 100% environmentally friendly water-based surface treatment, and the center console is made of Benecke suede PVC material, which feels excellent. The suede material absorbs strong light, and the shadow of the interior does not reflect on the front windshield. This is indeed better than what some luxury brands do.

　　The car-machine interface is not only visible, but also has gesture control functions. In addition, the automatic speech recognition ability of Yipai eπ 008 is very accurate, and it can also determine whether the voice is sent from the front or the back, so as to accurately identify the front and rear functions that need to be controlled.

　　The 9.2-inch streaming rearview mirror shows clearly, and the reflection is very weak. When the rear roof entertainment screen is turned on, the ordinary optical rearview mirror will be blocked by the screen. At this time, the streaming rearview mirror is very necessary, and it can be regarded as a safety configuration.

　　The front 50W mobile phone wireless fast charging, with ventilation function, Honor mobile phone can reach the level of extremely fast charging, basically charging for 1 minute, and the mobile phone power increases by 1%.

　　In addition to buying a large SUV, 200,000 people can also buy a refrigerator, color TV, and a large sofa. The Yipai eπ 008 is equipped with a 15.6-inch rear entertainment screen, which can be opened through the rear touchscreen or voice. For children, the rear entertainment screen can make them quiet faster, and for adults, long-distance travel will not be particularly boring.

　　The upper and lower dual touch screens in the rear row can adjust the heating and ventilation of the seats and the nap mode in the rear row; the touch screens below adjust the cooling and warmth of the refrigerator and move back and forth.

　　Yipai eπ 008 uses a semiconductor refrigeration refrigerator with a minimum temperature of 5 ° C and a maximum temperature of 50 ° C. It has an electric front and rear movement function and can be stopped on the slide at any time, making it convenient for passengers in the second and third rows to pick up drinks and items.　　

　　Of course, Yi Pai e π 008 also has a big sofa – a zero-gravity seat, in addition to supporting ventilation and heating, it also has a massage function, making long-distance travel more comfortable.

　　Yipai eπ 008 benefits from the 3025mm wheelbase, which makes the interior of the vehicle have a large "housing rate" of 67.4%. The direct benefit is that it has 6 large sofa seats, and everyone’s comfort is a mobile home.

　　In terms of details, Yi Pai e π 008’s control is also very good. There are 28 + 2 storage spaces in the whole car, and each row of passengers has its own exclusive cup holder. The trunk space can be flexibly arranged through baffle, which is really attentive.

　　The test drive this time is the Yipai eπ 008 pure electric version, which uses a 200kW rear single motor. From the actual driving experience, it is very easy to drive such a large SUV. The power reserve is good, even if the speed reaches 120km/h, the power can still be stepped on. The steering wheel is pointed more accurately, and the whole car is very flexible and does not feel bulky.

　　The most commendable thing is that the quietness of the whole vehicle is excellent, and it also meets the demands of family car users. With the blessing of Continental silent tires, double front windshield, double front and rear window glass, and the excellent NVH design and materials of the vehicle itself, it is almost impossible to hear obvious fetal noise and wind noise when driving at high speed.

　　Another commendable feature was the suspension tuning. Yi Pai E Pi 008 actually used the coil spring + shock absorber to adjust the feeling of the air spring. The fine road vibration was filtered very thoroughly, and the sharp bounce could be resolved in time.

　　Yipai eπ 008 is based on Dongfeng quantum architecture and is equipped with Dongfeng Mach E electric drive system. The maximum efficiency of the electric drive assembly is 94.5%. The comprehensive energy consumption of the pure electric model is as low as 14.7kwh/100km, and the CLTC battery life reaches 636km. In addition, the extended range model is equipped with the industry’s first extended range dedicated engine with a thermal efficiency of 45.18%. The CLTC pure electric battery life is 210km, the feed fuel consumption is as low as 5.55L/100km, and the CLTC comprehensive battery life is 1300km.

　　Yipai eπ 008 is equipped with 32 high-precision sensing hardware, including a black sesame A1000 chip, which supports high-speed NOA pilot auxiliary driving and has functions such as automatic up and down ramp and automatic lane change, which belongs to the level of L2 + intelligent driving.

　　With the launch of the eπ 007 medium and large sedan and the eπ 008, which will be officially launched in June, Dongfeng Yipai will continue to make efforts in the two power tracks of pure electricity and range extension, and compete head-on with mainstream new energy brands in the 15-250,000 level market. Looking forward to the future Dongfeng Yipai will bring more dazzling products and bring more new energy vehicle choices to consumers.

　　　 Movie Network News(Compiler/Ben) According to South Korean media reports, the director of the Korean film popular in Asia, Guo Zairong, will direct the Chinese costume blockbuster "Yang Guifei".

　　　 "Yang Guifei" will focus on the story of the ups and downs of the life of Yang Yuhuan, a beautiful woman in the Tang Dynasty. According to Korean media reports, Yang Guifei will be played by Fan Bingbing, while Zhou Yunfa will play the role of Emperor Xuanzong of Tang. At present, the crew is still in contact with Japanese actor Oda Che Rang, hoping to invite him to star.

　　　 In addition to Guo Jae-yong, a large number of Korean directors have been exploring the overseas film market. In response, the Korea Film Promotion Committee held a "China Film Market Status and Career Briefing Session" on April 4 this year, and made it clear through the briefing that "the entire Asian film market is increasingly concerned about Korean films and their infrastructure. In addition to the greater Chinese market’s interest in Korean films, the demand for Korean actors, directors, film practitioners and scripts is increasing." The committee also stressed the need for the Korean film industry to expand the infrastructure of software and hardware to cope with the long-standing cooperation projects between the film industries of the two countries.

　　　 For the "Concubine Yang" directed by Guo Zairong, Korean public opinion has also given high attention. For the female lead actor Fan Bingbing, Korean media are even more generous with praise, directly calling him "the most beautiful woman in the Chinese circle". In this regard, some Korean netizens also said that they are very much looking forward to seeing Fan Bingbing play the shape of Concubine Yang.

　　　 Fan Bingbing’s popularity in South Korea has also been on the rise in recent years. In South Korean media reports, Fan Bingbing’s face shape and facial features were first interviewed by Jiang Minjun, director of a well-known plastic surgery hospital in South Korea. The director introduced that Fan Bingbing is a typical Cross Line, that is, the vertical line from the forehead to the nose to the chin and the horizontal line of the left and right cheeks parallel to the nose are very balanced, which not only looks very comfortable, but also leaves a good impression. Fan Bingbing’s face shape and facial features are also the beauty that most Korean women like and envy. And the director himself also said that he is very much looking forward to the ancient Chinese beautiful woman Yang Guifei photographed by Guo Zairong.

　　　 Then, Korean media also reported the details of Fan Bingbing, including her birthplace and age, and mentioned that she had starred in the golden lock in the popular Korean TV series "Huanzhu Gege" at the age of 18 (1998).

　　　 The work that brought Fan Bingbing into the eyes of Korean audiences again was her romantic comedy starring Zhang Ziyi and Su Zhixie. Recently, after taking on the work directed by Jiang Digui, the news of her cooperation with Zhang Dongjian has also been frequently reported in the newspapers, and she has become a Chinese actress that has attracted the attention of Korean media.

　　　 Fan Bingbing and Andy Lau were originally scheduled to go to South Korea on August 11 to promote the film’s release in South Korea, but due to the producer’s mistake, the promotion trip was cancelled. The concentrated coverage of the matter in the Korean media and the disappointment revealed in the words can be seen from Fan Bingbing’s popularity in South Korea.

Recently, Q & A Auto officially announced that the new AITO Q & A M7 will be officially released in Shanghai on September 12. Previously, the new Q & A M7 has been officially unveiled at the Chengdu Auto Show. Huawei Managing Director, End Point BG CEO, and Smart Car Solutions BU CEO Yu Chengdong personally unveiled the new model. The listing is imminent, let’s take a look at what the new Q & A M7 has been upgraded to?

In terms of appearance, the new M7 still retains many of the styling features of the previous generation model, such as the super-long through-the-day running light belt, the "gills" vents on both sides, and the rounded body lines, as well as the simple and powerful taillights. The body size has also not changed. The length, width and height are 5020/1945/1760mm respectively, and the wheelbase is 2820mm. So it is almost difficult to tell from the outside which is the new M7 and which is the previous generation model.

Enter the car to find out what the new car is different from the previous generation model. First of all, in addition to the six-seat version, the new Wenjie M7 will also provide a large five-seat layout. The seat design in the car is softer and more comfortable, and the wrapping is stronger. The rear seat backrest angle is adjustable from 27 ° -36 °. Not only are the front and rear rows equipped with 8-point massage/ventilation/heating as standard, but the middle seat can also be heated, and supports a variety of flexible seat layouts. The rear Maglink interface supports dual expansion entertainment screens, which can be used to control the car system, in-car air conditioning, etc.

In terms of space, upgrade to 3338mm large effective space, higher than the ideal L7 Max, BMW X5L and other models of the same level. With a 1.1-meter-long trunk, it can accommodate 12 20-inch suitcases at the same time. There is also a hidden compartment in the trunk that can hold 50 bottles of mineral water. After the second row of seats is put down, the trunk volume can reach 1619L.

In the intelligent part, the new Q-world M7 will be further upgraded and optimized in the Hongmeng car-machine system and ADS intelligent driving assistance system. Among them, the new car will be equipped with ADS 2.0 advanced driver assistance system, which focuses on being more human-like, more active and more efficient. In addition, the Harmony OS in the central control screen will also use the latest version, and the picture clarity, dynamic effects, and human-machine interaction and in-vehicle application experience will also be better.

As for power, the new car will continue to be equipped with an extended range power system composed of a 1.5T four-cylinder range extender and a Huawei motor, and provide two-wheel drive and four-wheel drive options. However, the maximum power of the 1.5T range extender is increased to 112kW. Among them, the rear-drive version is equipped with a drive motor with a maximum power of 200kW; the four-wheel drive model adds a drive motor with a maximum power of 130kW to the front axle, and the comprehensive power of the system is 330kW. Both are matched with a 40.06kWh battery pack, and the pure electric cruising range is not much different from the current model.

The body structure and intelligent driving of the New World M7 have been upgraded, which has greatly improved the safety. Structurally, due to the change of 6 seats to 5 seats, the body needs to be re-matched to open the mold. The body material uses "the industry’s strongest submarine-grade high-strength steel and CBS composite body material" and advanced technology. With the support of the cage body structure design, the submarine-grade thermoformed steel accounts for 24.4% of the whole car, high-strength steel and aluminum alloy account for more than 80%, and can withstand 17 tons per square centimeter.

Wenjie’s new M7 is equipped with 1 lidar, 3 millimeter wave radars, 11 high definition cameras, and 12 ultrasonic radars. This is a multi-sensor fusion sensing system that can achieve 360-degree full-range coverage and can detect up to 200 meters. In addition, there are intelligent driving assistance systems, automatic parking and other functions, ELKA lateral anti-collision system, LAEB low-speed anti-collision, small animal automatic identification, LCC + lane cruise assistance enhancement, and laser radar fusion sensing system. Intelligent safety configurations such as the system greatly enhance the convenience and safety of driving, and fully escort users’ travel!

The investment in vehicle safety of the new Q & J M7 is worthy of recognition. It is also a wise decision to change the six seats to five seats on the basis of the original space volume. The upgrades in these two aspects further strengthen the competitiveness of the model. However, if you want to become a hot-selling model in the market segment, the new Q & J M7 still has a lot of homework to do, such as product marketing and promotion, how to make consumers perceive the advantages of this car, etc… However, I personally think the foundation of the new Q & J M7 is still very solid, and it is a good car worth looking forward to. What do you think?