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Original Socrates’ afternoon tea medical rheumatism immunity channel

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AAV is a systemic necrotizing vasculitis involving multiple organs and systems.

Recently, a summary of clinical practice on the diagnosis and treatment of ANCA-associated vasculitis (AAV) was published in Rheumatology. Let’s take a look at what dry goods are available ~

Figure 1: Screenshot of this overview.

Performance of AAV

AAV is a group of systemic vasculitis characterized by the detection of ANCA in serum, which mainly involves small blood vessels. It is characterized by full-thickness inflammation, necrosis and granuloma formation in small blood vessels.

Common symptoms can be manifested as fever, joint pain, myalgia, fatigue, weight loss, etc. When lung, kidney, gastrointestinal tract, nervous system and five senses are involved, corresponding clinical manifestations will appear. Musculoskeletal symptoms of the whole body are not specific, but they are common; The following clinical manifestations can also occur alone or in combination: chronic recurrent sinusitis accompanied by nasal scab, hollow pulmonary nodules, rapidly progressive necrotizing oligoimmune complex glomerulonephritis, multiple mononeuropathy, pericarditis or myocarditis and obvious purpura, while respiratory and renal failure at the same time is called "pneumorenal syndrome", which is an acute and severe manifestation of AAV.

Generally speaking, multiple organs and systems involved at the same time and obvious inflammatory reaction are often the key clues to diagnose AAV.

How to diagnose?

1, patient evaluation and diagnostic evaluation

When the diagnosis of AAV is suspected, a comprehensive clinical evaluation should be conducted to assess whether all the organs that may be involved are involved (see Table 1).

Table 1: Patient Assessment and Diagnostic Assessment

Routine blood tests should be carried out, and alveolar hemorrhage should be highly suspected if there is a continuous decrease in hemoglobin level.

Urine analysis is essential in finding hematuria, proteinuria and urine culture to eliminate infection, and the detection of proteinuria needs to be evaluated by quantitative urine protein/creatinine ratio.

All patients underwent chest X-ray examination. When respiratory involvement (such as alveolitis, pulmonary infiltration or nodules) is suspected, chest CT examination should be conducted in time.

When ENT involvement is suspected, CT examination of paranasal sinuses must be performed and evaluated by ENT experts (including nasal and laryngeal fibroscopy, etc.).

Electromyography was performed when peripheral nerve involvement was suspected.

In a word, it is suggested to carry out multidisciplinary examination according to the organ system involved.

2. The value of ANCA screening

It is strongly recommended to screen ANCA, and the detection of protease 3(PR3)-ANCA and myeloperoxidase (MPO)-ANCA is highly specific.

In the meta-analysis of evaluating the value of ANCA, the sensitivity and specificity of anti-PR3 antibody were 80% and 93%, while the sensitivity and specificity of anti-MPO antibody were 58% and 96%. The specificity of ANCA was different between granulomatous vasculitis (GPA) and microscopic polyangiitis (MPA), with PR3-ANCA positive accounting for 78%-87% in GPA and MPO-ANCA in MPA.

ANCA was not detected in the blood of about 10% patients with GPA and MPA, reminding us that there may be other biomarkers that have not been found when considering the diagnosis of AAV.

Besides AAV, ANCA is occasionally found in some patients with infection, other autoimmune diseases and other vasculitis.

3. When will the biopsy be performed?

Biopsy of kidney, lung, nose, nerve and muscle tissue can provide reliable evidence for the diagnosis and differential diagnosis of diseases.

The diagnostic rate of pathology may vary significantly with different biopsy sites. For example, renal biopsy has a high diagnostic rate, while paranasal sinus biopsy often suggests nonspecific inflammation.

Although biopsy is the gold standard and strongly recommended, in clinical practice, when the clinical manifestations are consistent with ANCA detection, biopsy can be omitted. In the latest classification standards of American Rheumatology Association (ACR) and European Union Against Rheumatism (EULAR) in 2022, when other diseases simulating vasculitis are excluded and diagnosed as vasculitis, biopsy is not a mandatory standard.

In short, biopsy (especially renal biopsy) should always be considered for patients suspected of active disease to evaluate the condition.

4. Classification criteria of MPA and GPA

At present, there is no diagnostic standard for AAV, so clinical manifestations, histological and laboratory data are very important for diagnosis.

Figure 2: GPA classification standard updated by 2022 ACR/EULAR

Figure 3: MPA classification standard updated by 2022 ACR/EULAR

The total score ≥5 points can diagnose GPA or MPA.

Treatment

1. Glucocorticoid

When the diagnosis of AAV is suspected, GC should be started, and the initial measurement is 1mg/kg prednisone (or equivalent) per day, or 500-1000mg methylprednisolone intravenously for 3-5 days.

PEXIVAS research shows that for critically ill patients who initially received methylprednisolone shock therapy, the GC dosage is reduced faster than that of the traditional regimen, that is, prednisone is reduced to 20mg per day within 7 weeks after starting treatment and 5mg per day within 19 weeks, which is as safe and effective as the standard dosage. The research shows that the risk of serious infection is low within one year.

LOVAS study showed that the initial remission of AAV (inanimate/severe organ involvement) was induced by GC of 0.5mg/kg/ day. As RITAZAREM study showed, the incidence of hypogammaglobulinemia (IgG<5g/L) was halved during the follow-up period.

It is mentioned that GC should be gradually reduced after induction of remission, and may be stopped gradually within the first year after diagnosis. At present, there is no high-quality evidence to support the need to maintain the optimal dose and duration of GC for AAV remission, so GC treatment should be individualized.

2. Immunosuppressive drugs that induce remission

① severe AAV

GC combined with cyclophosphamide (CTX) or rituximab is the standard scheme to induce severe disease remission at present, although more and more evidence shows that in some subgroups of patients, such as PR3-ANCA positive patients and patients with disease recurrence, rituximab is better than CTX to maintain fertility.

CTX can be administered intravenously or orally, and the dosage should be reduced in elderly patients with renal insufficiency. The dosage of 15mg/kg is selected according to the most widely used CYCLOPS regimen in Europe. Compared with the daily oral regimen (2mg/kg/d), the cumulative dosage of CTX can be reduced by 50%, and the remission rate is similar, while the end-stage renal disease, adverse events or survival time have not increased, but the risk of disease recurrence has increased in the long run.

The two regimens usually stop taking drugs 3-6 months after remission, and then start maintenance treatment.

Rituximab (375mg/m2 per week, four times in total or 1000mg twice every two weeks) is not inferior to CTX in inducing remission, and it is more advantageous in PR3-ANCA positive or recurrent patients.

There is little evidence to compare CTX with rituximab in patients with low glomerular filtration rate (< 20 ml/min/1.73m2). According to the suggestion of KDIGO guidelines in 2021, in addition to the first and third intravenous use of 15mg/kg CTX, such patients can also choose to use 375mg/m2 of rituximab combined with CTX for four consecutive weeks. However, this combination may bring additional risk of infection, and a recent retrospective study showed that rituximab alone may be as effective as CTX in inducing remission in patients with eGFR<30ml/min/1.73m2.

In all patients, compound sulfamethoxazole should be taken orally for at least 3 months after the last use of CTX to prevent pneumocystis carinii pneumonia (atrovaquinone or pentamidine aerosol should be used in case of intolerance/allergy) until B cells are rebuilt after rituximab treatment.

② Non-severe AAV

For non-serious disease-induced remission, rituximab is more effective than conventional immunosuppressants, and MTX and MMF can be used as substitutes when rituximab or CTX cannot be used. Studies have shown that MTX and MMF are not inferior to CTX in the remission rate of 6 months, but the recurrence rate during follow-up is higher than CTX, especially in PR3-ANCA positive patients.

3. Immunosuppressive drugs to maintain remission

After CTX or rituximab combined with low-dose GC induction therapy, rituximab (500 mg every 6 months) is superior to azathioprine in the maintenance and remission of GPA and MPA. It has been proved that the maintenance treatment of rituximab (1000mg once every 4 months) is safe and effective in patients with recurrence. For patients with contraindications to rituximab, AZA or MTX can be considered as alternative therapy.

On the other hand, the use of rituximab may lead to hypogammaglobulinemia and increased risk of infection, so it is suggested to use low-dose rituximab to maintain remission. In clinical practice, not only drug safety but also the risk of disease recurrence should be considered.

AZA(2mg/kg/ day) and MTX(0.3mg/kg increased to the maximum of 25mg/ week) have similar effects on maintaining remission of AAV, and they are second-line drugs for maintaining remission. Patients with impaired renal function (eGFR<45ml/min) should avoid using MTX.

At present, EULAR recommends maintaining treatment for at least 2 years, and recent studies using rituximab or AZA regimen show that immunosuppressive treatment for more than 2 years can reduce the recurrence rate of the disease.

4, plasma exchange and complement C5 receptor inhibitors

PEXIVAS research shows that routine plasma exchange treatment for severe GPA/MPA patients with glomerulonephritis (eGFR<50ml/min/1.73m2) or alveolar hemorrhage has no benefit. This result is contrary to the previous MEPEX1 study, which may be due to the stricter inclusion criteria of the latter [creatinine (> 5.8mg/dl) and glomerulonephritis confirmed by biopsy are required]. The subgroup analysis of PEXIVAS study showed that plasma exchange did not benefit significantly in these subgroups.

Meta-analysis published recently shows that plasma exchange at the age of 12 months in patients with severe renal disease may be beneficial to the prognosis of kidney if the infection rate is high.

Therefore, even with severe renal disease, the use of plasma exchange is still controversial, and it is not recommended as a routine treatment.

It is worth noting that the position of international guidelines on plasma exchange of AAV is quite different. The KDIGO Alliance recommends plasma exchange for patients who need dialysis or whose creatinine increases rapidly > 500 mol/L (> 5.8 mg/DL), or for patients with severe hypoxemia and alveolar hemorrhage, while the 2021 ACR guidelines suggest that plasma exchange is not recommended for patients with active AAV glomerulonephritis or alveolar hemorrhage. EULAR 2022 suggested that plasma exchange should be considered in patients with rapid increase of creatinine > 300μmol/l, but there is no evidence that routine plasma exchange can treat alveolar hemorrhage.

Recently, in addition to CTX or rituximab, avacopan, an oral complement factor C5 receptor inhibitor, has been approved and licensed for the induced remission and maintenance treatment of severe AAV, in order to replace or limit the dosage of GC.

So which patients will benefit the most from this new treatment, especially considering the cost of the drug, is still worth discussing.

According to the study of its mechanism of action, avacopan seems to be the most useful for patients with severe kidney disease and alveolar hemorrhage, as well as patients with high risk of GC-induced comorbidity, including the elderly.

summary

When the patient is highly suspected of AAV, further ANCA detection is needed, and all organs are evaluated, and if necessary, tissue biopsy is performed to make a definite diagnosis.

Clinical treatment strategies should vary according to the severity, age, weight, complications and prognosis of AAV.

Recent studies support rituximab as the first choice to induce and maintain remission.

In addition, compared with the conventional scheme, a small amount of GC is equally effective and safer in inducing remission.

There is insufficient evidence to support the routine use of plasma exchange for treatment.

References:

Baptiste Chevet, Divi Cornec, Marta Casal Moura, Emilie Cornec-Le Gall, Diagnosing and treating ANCA-associated vasculitis: an updated review for clinical practice.[J] Rheumatology.

This article is the first channel of rheumatism immunity in medical field.

The author of this article is Socrates’ afternoon tea.

This article reviews Chen Xinpeng, Deputy Chief Physician.

Responsible editor, cassette tape

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Smart rice cookers, large-capacity commercial rice cookers, multifunctional electric cookers … In the online exhibition area of Canton Fair of Guangdong Huaqiang Electric Appliance Group Co., Ltd., a dazzling array of small household appliances attracted many buyers to stay in the exhibition area. "In the past few days, the company has reached cooperation with 12 customers, and the order amount is about 650,000 US dollars." Lu Runhua, general manager of the company, said with satisfaction.

From April 15th to 24th, China Import and Export Fair (Canton Fair) was held for the fourth time. The cumulative number of visitors in official website is 10.09 million, with 33.9 million visits; 536,000 overseas buyers from 228 countries and regions registered to watch the exhibition, which was 41.8% higher than the 130th session … The enthusiasm for participating in the exhibition was high and online transactions were busy. The "cloud" Canton Fair set up a unique economic and trade bridge for Chinese and foreign exhibitors and buyers.

Stable scale, more new products.

Canton Fair is regarded as a "barometer" and "weather vane" of foreign trade. The overall scale of the Canton Fair has remained stable, and the quality of exhibitors has steadily improved. According to Xu Bing, spokesman of Canton Fair, there are about 25,500 exhibitors at home and abroad, and 50 exhibition areas are set up according to 16 categories of goods. Domestic and foreign exhibitors uploaded a total of 3,052,100 exhibits, including 951,500 new products, all of which reached record highs.

Held continuously for more than 60 years, the Canton Fair has accumulated a large number of "fans". Although affected by the epidemic situation in COVID-19, exhibitors and buyers are enthusiastic and full of gains with the help of various new technologies and forms, such as pictures, texts, videos, 3D and VR.

"Six consecutive broadcasts a day!" Wang Dingying, deputy general manager of Ningbo Yongtaiping Import and Export Co., Ltd. said excitedly. The company’s products cover 14 exhibition areas of the Canton Fair, covering hardware, clothing, home accessories, shoes and bags, office appliances, consumer electronics, home appliances and many other categories. Wang Dingying introduced that the live broadcast of household appliances is the most popular, and new small household appliances such as coffee machines and wall-breaking machines were welcomed by buyers in India, the Philippines and other countries as soon as they appeared. "As long as customers need it, we are not afraid of being tired."

High-tech content and many new products are the highlights of this year’s Canton Fair.

On April 17th, at the launch event of new products in Canton Fair, a VR game device named "Lexiang Go-kart" attracted much attention. This product of Guangzhou Zhuo Yuan Virtual Reality Technology Co., Ltd. adopts the patent of crank technology, and brings people a realistic driving experience through the steering wheel, throttle, brake and blowing special effects. "With the guidance of’ fist products’, we have reached an intentional transaction amount of 360,000 US dollars at this Canton Fair." The person in charge of the company said.

Compared with previous years, more exhibitors launched their own research and development, independent brand exhibits, and made new achievements. Following the international fashion trend, the "high-value" aluminum cookware and the stainless steel cookware with thumb groove on bakelite handle … A large number of new products of Shanghai Longtou Import & Export Co., Ltd., a subsidiary of Dongfang International Group, have attracted many overseas buyers for their novel design, excellent materials and close market demand.

Practicing the concept of "creating green", green and low-carbon products have become a hot topic in this Canton Fair.

"Bamboo will not cause soil erosion when it is cut down, and its growth cycle is faster. It can replace trees as raw materials for production and play a role in protecting the environment and saving resources." Feng Limei, general manager of Foshan Meijia Green Environmental Protection Materials Co., Ltd. introduced that the company brought many new environmentally-friendly bamboo products at the Canton Fair, including degradable PLA cups and environmentally-friendly lunch boxes. "The epidemic has affected consumers’ living and eating habits, which has greatly increased the demand for disposable tableware, and our degradable tableware has gained a lot of negotiation intentions."

"Buy the world, sell the world" on the cloud.

"Cloud" exhibition, how to make the supply and mining better docking?

This year’s Canton Fair held 50 "Bridge of Trade" cloud promotion activities around the world, providing accurate docking services for multinational head enterprises and domestic key industrial clusters and brand enterprises, and enhancing the effectiveness of trade matching. The mascots of the Canton Fair "BEE" and "HONEY" became online recommenders, and eight trade promotion and matching activities of "Haobao and Haoni exploring and making friends" led millions of overseas fans to experience the Canton Fair in an immersive way. At the same time, the online platform was further optimized. For the first time, enterprise and product characteristic signs such as specialization, novelty, high-tech, green and low-carbon, and intelligent products were added, and the function of authorizing buyers’ information was added to make the platform more fluent and responsive.

In order to fit the characteristics of "cloud", exhibitors have adjusted their strategies to improve the "sense of presence" of product display through virtual reality and augmented reality technology. Ningbo Zhongji Huitong Group Co., Ltd. built a 3D online exhibition hall to provide buyers with a "360-degree no dead angle" exhibition experience. Ying Xiuzhen, vice president of the company, said: "Our exhibition hall has realized the dream linkage between virtual and reality. After wearing VR equipment, foreign businessmen can experience products more intuitively."

The Canton Fair moved to the "cloud", and exhibitors overcame the obstacles of time difference and distance to attract customers and open up markets.

Guangzhou Gao En Machinery Technology Co., Ltd. adjusts the online activity arrangement according to the time difference of customers, and informs new and old customers in advance. "The first online display after the opening ceremony lasted only 1 hour and 44 minutes, and the total number of likes reached 420,000. In the afternoon, the company arranged two online exhibitions, and soon received purchasing intentions from overseas buyers such as Mexico, Chile, India, Russia, Colombia, Spain and Germany. " Huo Liyi, general manager of the company, said.

According to the time difference of different customer groups, Haida Gate Control Co., Ltd. has set up a six-time online display. "In recent days, we have received dozens of customer inquiries, and the total amount of intentional orders has reached 148,000 US dollars." Liu Chunlin, the company’s foreign trade manager, said.

After watching the online exhibition of Oulusha Co., Ltd., Bangladeshi buyer Idis became interested in the bathroom cabinets and smart toilets produced by Oulusha, and finally reached the first intentional order of 300,000 US dollars. "Oulusha’s products are novel and full of design sense. We have learned about the whole company in detail in the online display, and we are also looking forward to visiting the factory in China after the epidemic." Idis said.

Overseas exhibitors are also full of gains. Spanish soap, Chilean red wine, Turkish coffee pot, Korean mask, German bearing … In the online import exhibition area of Canton Fair, 402 overseas enterprises from 32 countries and regions around the world exhibited many delicious, fun, good-looking and easy-to-use goods. Afghan exhibitor Ali brought a variety of high-quality products such as handmade blankets and pine nuts. He lamented: "China consumers have strong demand and purchasing power for high-quality specialty products."

According to statistics, during the current Canton Fair, the total number of visitors to the cloud exhibition hall of exhibitors was 6,223,100, and exhibitors held a total of 85,300 online exhibitions.

Unicom’s domestic and international double circulation

Recently, domestic epidemics have occurred frequently, and the production and business activities of some foreign trade enterprises have been limited, and logistics and transportation have been blocked. In this context, the significance of "Unicom’s domestic and international double cycle" in this Canton Fair has become increasingly prominent.

Expand the "circle of friends" to build a high-quality platform for foreign trade enterprises and create more business opportunities.

There are 170 global partners in this Canton Fair, including 50 partners from countries along the Belt and Road and more than 40 partners from RCEP member countries, achieving full coverage of RCEP member countries. "The Canton Fair is the golden signboard of China’s foreign trade development, and it has accumulated a huge credit advantage for more than 60 years. With the platform of the Canton Fair, we have established long-term cooperative relations with many domestic and foreign customers. " Lin Xiaofeng, vice president of overseas marketing of Shenzhen Tuori New Energy Technology Co., Ltd. said.

Improve the support ability and facilitate enterprises to "go out to sea".

In order to alleviate the difficulties of foreign trade enterprises in "finding ships" and "finding cabinets", this year’s Canton Fair has set up a trade service section, which is divided into four categories: testing and certification, cross-border e-commerce, logistics and transportation, and comprehensive services, covering 26 logistics and transportation enterprises, 7 cross-border e-commerce enterprises and 4 comprehensive service enterprises, and set up a cross-border e-commerce area to escort the order fulfillment of participating foreign trade enterprises.

Promote the integration of domestic and foreign trade, and help foreign trade enterprises to "walk on two legs" in export and domestic sales.

Shanghai Guanhua Stainless Steel Products Co., Ltd., a veteran foreign trade enterprise, was hit by the epidemic, and some orders were cancelled or delayed, resulting in a backlog of inventory. Through the Canton Fair, enterprises can get to know more domestic buyers, build their own brands and explore the domestic market. At present, the company’s domestic products account for 20% of the total sales.

Behind the strong popularity of the Canton Fair is the China market with unlimited business opportunities and the resilient China economy.

For seven consecutive quarters, the year-on-year growth was positive. In the first quarter, the total import and export value of goods trade was 9.42 trillion yuan, up 10.7% year-on-year … The outstanding performance of China’s foreign trade has conveyed confidence and strength to Chinese and foreign exhibitors in this Canton Fair. Becca Meka Belize, president of the Georgian Chamber of Commerce and Industry in Guangdong Province, believes that the "cloud" Canton Fair has provided solid support for ensuring the stability of the global industrial chain supply chain and injected strong impetus into the global economic recovery. "The creative Cloud Canton Fair fully embodies the wisdom of China, which has opened up new trade channels for me. The market in China is very broad, and I have sufficient confidence to dig deep in this layout. " Becca said.

In the long run, how to build a "Digital Canton Fair" with high standards and high quality? Wang Shouwen, Vice Minister of Commerce, said that China will open wider to the outside world, and the Canton Fair will also play a more important role in this process. In the future, the online exhibition of the Canton Fair will innovate mechanisms, enrich formats and expand functions, and realize the integrated development of online and offline. "The Canton Fair will continue to improve the service level for exhibitors and strive to provide more display channels and service content; Continue to increase the invitation of professional buyers, and strive to achieve the increase of buyers’ participation enthusiasm, stable quantity, optimized structure and improved quality; Continue to create a safe, reliable and mutual trust exhibition environment, and strive to make the platform more stable, more functional and more effective. " Wang Shouwen said. (Reporter Wang Wenzheng)

Before talking about extreme yue, it is necessary to talk about Wei Lai first.

In November, Weilai Automobile achieved a sales volume of 20,575 vehicles. Although 5,082 of them were contributed by the second brand Ledao, in any case, from the total sales volume of the two major brands, Weilai Automobile has stabilized at more than 20,000 vehicles for seven consecutive months. In the new power camp of independent pure electricity, this achievement is the existence of the top five, the absolute head echelon!

In addition to sales, look at the financial report. As we all know, up to now, Weilai Automobile has not achieved profitability.

In the first three quarters of this year, the quarterly net loss of Weilai Automobile exceeded 5 billion yuan. Looks dangerous, doesn’t it? However, according to the third quarter financial report, Weilai’s gross profit margin has not only increased to 13.1%, but also its free cash flow has turned positive, which means that Weilai Automobile has the ability of self-hematopoiesis and its financial health is continuously improving.

In addition, Weilai Automobile has lost tens of billions in recent years, which is also related to Weilai Automobile’s huge investment in the field of power exchange. In the past year or so, Weilai Automobile has signed power exchange strategic agreements with many domestic mainstream car companies, and the power exchange alliance with Weilai as the link is growing.

With the gradual landing of the power exchange layout of various car companies, this is a signal that Weilai is expected to enter the "payback period". You know, the alliance is getting bigger and bigger, car companies share the cost, the standards are gradually unified, and Weilai will invest less and less in the field of power exchange.

In terms of technology, from intelligent cockpit to intelligent driving, from chip to operating system, Weilai has laid a good foundation, and the next "building" speed will only get faster and faster. This year marks the tenth anniversary of Weilai’s founding. It is said that Weilai may release a third brand firefly in the upcoming NIO day 2024.

There is no other reason for saying so much, just to prove that Weilai Automobile is continuing to improve.

What’s the matter with Guan Ji Yue? When Xia Yiping, CEO of Jiyue Automobile, communicated with all employees through video conference, Xia Yiping mentioned that the following four things need to be done when the company enters the 2.0 stage of entrepreneurship: 1. Adhere to the long-term investment in core technologies to maintain the leading edge; 2. Strengthen sales and service capacity building to cope with fierce market competition; 3. Merge departments and posts with duplicate functions and change inefficient internal workflow; 4. Reduce projects that cannot improve financial performance in the short term.

Are these four measures familiar? About a year ago, Weilai Automobile was experiencing the second "bankruptcy rumor".

At that time, Li Bin’s internal staff letter "Organizational Optimization and Two-year Priorities" mentioned Weilai Automobile’s organizational and business optimization plan: to ensure long-term investment in core key technologies and maintain the leading edge of technology and products; Ensure that sales and service capabilities can cope with fierce market competition; Ensure that 9 products of 3 brands are listed as scheduled; Organize and improve efficiency, merge redundant departments and posts, and change inefficient internal workflow and division of labor; Improve the efficiency of resources, postpone and reduce the project investment that can not improve the company’s financial performance within 3 years.

Comparatively speaking, the similarity between Ji Yue and Wei Lai’s "self-help" plan is at least 90%, right?

It is a compulsory course for rulers of past dynasties in historical civilization to learn from others’ experience and spur themselves, and it is also a truth that quality education has taught for a long time. A year ago, Wei Lai, like Ji Yue now, faced a "big test" about life and death. Now Weilai has stepped out of the quagmire of public opinion. Even though there are still losses, there are still challenges in development. However, compared with the situation of "life and death" in 2019 and the situation a year ago, Weilai has greatly improved.

Whether Xia Yiping copied it or carefully pondered Weilai’s organizational optimization strategy, it seems that there is nothing wrong with taking the road of Weilai Automobile. Stabilizing the storm of public opinion, strengthening superficial confidence, reducing staff and costs, and cutting down projects with large investment are indeed things that need to be done at present. Only by doing these things well can we survive.

However, Xia Yiping seems to have overlooked one thing. In the past ten years since its establishment, Weilai Automobile has suffered a bankruptcy storm, and it has been on the verge of life and death for several times, with a loss of nearly 100 billion yuan. However, Weilai Automobile’s pre-sales and after-sales service, power exchange advantages, user reputation, technology matrix and high-end brand tonality all have Weilai characteristics. In the fierce market competition, Weilai Automobile is not a fight with bare hands.

However, in order to do these characteristics well, Weilai Automobile’s excessive investment in marketing and huge investment in changing power stations really need to be "changed" through the optimization of organizational structure. In other words, what Wei Lai mainly needs to change is the thinking and mentality of spending money lavishly.

This is the difference between Extreme Yue and Weilai, and it is also the reason why the organizational structure optimization strategy of Weilai Automobile may be difficult to apply to Extreme Yue.

From the birth point of view, as a new force car enterprise that Baidu and Geely Automobile cooperate, it is more reasonable to say that it is a new force car enterprise born with a golden spoon, which has more foundation than the new cross-border forces such as Weilai, Tucki and Ideality. However, the design at the product level is too advanced, the pricing is not close to the people, and the impression of the organization level, the secret game between the two companies, the disagreement of the leadership and other factors has finally failed to make Extreme Yue "an instant hit".

Since it went public in October last year, its sales have not improved much. After the price reduction again in July this year, the Extreme Yue 01 has a certain growth, but it has gone downhill since it sold 2147 units in August. As the second model of Extreme Yue, it has learned the experience of Extreme Yue 01, and the price in one step has finally made Extreme Yue "proud" in the vertical sense, with orders exceeding 5000+ within 48 hours of listing.

From September to November, the sales volume of Extreme Vietnam in 2007 was 927, 1936 and 1030 respectively. Although it is much better than the data of Extreme Yue 01, we should know that the medium and large pure electric car market where Extreme Yue 07 is located is not only full of strong rivals, but also its monthly sales volume has exceeded 20,000 vehicles for two consecutive months, and the latest Tucki P7+ has achieved 6,950 vehicles in the first month of listing.

Compared with the sales of most models of the same class, Extreme Yue 07 has also become an "upset".

It is worth mentioning that, although Extremely Yue has always emphasized that it is the best car company in intelligent driving, as of now, Extremely Yue has not opened the city pilot, and the label of the strongest intelligent driving has not been set up, while the other three power companies, chassis and architecture, mainly rely on Geely’s output. In other words, there is almost no visible capital that can make capital and market trust again.

What does this mean? It means that the process of "actively promoting financing" mentioned by Ji Yue will be very difficult, and it also means that it may be difficult for both shareholders to rekindle confidence. Since the release of Taizhou Declaration, Geely has moved from strategic expansion to strategic focus. On the basis of focusing on Great Geely and Great Krypton, it may be difficult for Geely to be distracted.

According to media reports, Extreme Yue has not only owed Geely a lot of OEM expenses and suppliers’ payment, but Baidu is not optimistic about the prospect of achieving profitability for Extreme Yue, so it chooses to stop loss in time. Of course, there is also a saying in the industry that Baidu is willing to continue to invest, but only if Xia Yiping must leave the CEO position.

No matter what the facts are, Baidu’s timely stop loss or watching the fire from the other side, from the rumor of bankruptcy to the rapid fermentation and spread in the industry, to the extreme crossing of Xia Yiping by employees, to the extreme crossing of the line of life and death, and now it is basically isolated and helpless.

In the eyes of many people, the ending of the extreme leap seems to have been doomed.

It is true that in recent years, the new car companies, once Weimar, Baiteng, Aichi, etc., have been gradually forgotten by the market. The high merger at the beginning of the year did not usher in a real reversal on schedule. The joint venture established by GAC and Weilai did not wait for the support of both shareholders, and Nezha, who was deeply involved in the rumors of bankruptcy, even though it was rumored again and again, the storm continued …

There are too few car companies like Weilai Automobile that have rallied from a state of near delisting and re-emerged. However, Ji Yue is not Weilai and Xia Yiping is not Li Bin, so it is hard for the market to believe that Ji Yue can become a new miracle.

Of course, for Xia Yiping, who is surrounded by employees, this philosophical problem is obviously not what he has time to think about.

Red dot observation:

From the Gaohe Ding Lei at the beginning of the year to the extreme Yue Xia Yi Ping at the end of the year, history is once again staged, and the whistle of the knockout stage is pressing. Ji Yue will not be the last one, and Xia Yiping will not be the last one. In the end, we still don’t know what the ultimate outcome is, whether it’s going against the sky or really "dissolving" on the spot, but what is certain is that it will never be easy and simple to get through this difficulty.

　　Introduction:In recent years, public security organs around the country have further simplified administration and decentralized power, innovated management and optimized services around the vital interests of the people, and constantly promoted the implementation of public security traffic management reform measures, which have been widely praised by the society and the masses. Let’s review the new convenience measures that have achieved remarkable results in 2017 and are closely related to our lives.

　　New measures of public security reform to facilitate the people and benefit the people

　　Keywords: hukou and residence permit, certificate issued by police station, convenience and benefit service platform.

　　First, the comprehensive reform of the household registration system

　　Focus on promoting the urbanization of agricultural transfer population, speeding up the implementation of the residence permit system, solving the problem of non-hukou registration, promoting the acceptance of resident ID cards in different places, cleaning up and rectifying household registration management, improving the timeliness of household registration, and unblocking the supervision channels for household registration.

　　Up to now, 23,613 cross-provincial acceptance points for resident identity cards have been set up in various places, handling more than 11.49 million resident identity cards and issuing more than 50 million residence permits for the masses in different places; There were 38,000 windows for reporting the loss and claiming lost property, and more than 9.07 million pieces of information were accepted for reporting the loss. The problem of more than 13 million people without registered permanent residence left over from history was basically solved.

　　Second, the certificate issued by the police station is simplified

　　In accordance with the principles of "according to the law" and "who is in charge, who is responsible", unnecessary certificates and procedures have been thoroughly cleared, and the types and quantities of certificates issued by police stations have generally dropped sharply. Chongqing, Jilin, Hunan, Zhejiang and other places have integrated more than 48 billion pieces of basic information, further promoted information sharing among departments, and provided information verification in 93 batches for more than 60 million people.

　　At the same time, local public security organs actively promote the collection, integration and sharing of departmental data, and strive to "let the data run more and let the people run less errands". According to statistics, the types of certificates in Jilin, Chongqing, Sichuan and Xinjiang decreased by 82%, 82%, 85% and 87% respectively, and the number of certificates issued in Liaoning, Heilongjiang, Hunan, Zhejiang, Guangdong and Hainan decreased by about 40%, 67%, 26%, 36%, 23% and 20% respectively.

　　Third, the "internet plus" household administration convenience Huimin service launched innovation

　　Henan, Heilongjiang and other places launched the "internet plus" service platform, which simplified the procedures, continued to introduce measures to facilitate the people and enterprises, innovated the service methods of public security and household registration, and actively responded to the people’s new demands and expectations for police work.

　　Among them, Henan Province has launched the "internet plus" household administration convenience service platform, and since the opening of the "Henan Police-People Connect" mobile APP and the "Henan Public Security Micro-Police Service" WeChat service number, it has opened up all aspects of online real-name authentication, online payment, online mailing and other online procedures, and realized 29 household administration services such as birth registration and house purchase. Since the platform was launched, it has handled 54,800 household registration businesses submitted by the masses, which has become the main business content of the largest "internet plus Government Affairs" comprehensive service platform in the province.

　　(The picture shows the public security police introducing the "Henan Police-People Connect" mobile APP and the "Henan Public Security Micro Police" WeChat service number to the masses. )

　　Measures to facilitate the people and benefit the people in traffic service management

　　Keywords: driving test reform, vehicle inspection reform, license plate management reform

　　First, the driving test reform was launched.

　　Since the reform of self-driving test was successfully started and implemented, it is more convenient to study driving, and the quality of driving school training service has also improved.

　　Online self-registration:All the 31 provinces in China have opened the Internet to take their own exams, and 247 million people have taken exams online, which has achieved a fair distribution of exam resources. There are 1097 new examination rooms in China, and 901 counties and cities have carried out all-subject examinations for small cars.

　　Measures to facilitate the people and benefit the people are fully implemented:A series of service measures have been fully implemented, such as releasing the examination and replacement in different places, relaxing the driving conditions for disabled people and optimizing the medical examination requirements for the elderly. At present, 86,000 people have applied for the driver’s license of large vans in different places, 5.657 million people have renewed and verified their driver’s licenses in different places, and 54,000 people with visual impairment and upper limb disabilities have obtained their driver’s licenses. More than 11 million elderly drivers aged 60 to 70 no longer undergo annual physical examination.

　　Second, the reform of vehicle inspection continued to advance

　　Since the implementation of vehicle inspection reform, local public security traffic management departments have actively cooperated with quality inspection departments to effectively promote stricter and more standardized vehicle inspection, fairer and fairer market and more convenient and efficient service.

　　Effective solution to the problem of "difficult vehicle inspection";There are 1,832 new automobile inspection agencies and 3,450 inspection lines in China, with an increase of 57.7% and 61.2% respectively, effectively solving the problems of difficulty in vehicle inspection and long queues, and the situation of illegal intermediary disturbing people and illegal charges has also been significantly reduced.

　　Vehicle inspection is faster and more convenient;The six-year exemption for private cars, the exemption for new cars, the appointment for inspection, and the inspection in different places in the province were fully implemented. 328 cities including Beijing launched the appointment inspection service and the inspection on Saturdays and Sundays continued. 154 million private cars enjoyed the exemption policy, and 19.76 million car owners realized the inspection in different places in the province.

　　More standardized development of vehicle inspection industry;Information-based remote supervision platforms have been established in various places, and 816 illegal inspection institutions have been investigated and dealt with, and 89 serious illegal inspection institutions have been revoked, effectively purifying the inspection industry and significantly improving the standardization of vehicle inspection.

　　Three, the smooth implementation of motor vehicle license plate management reform.

　　In May this year, the Ministry of Public Security officially launched the reform of motor vehicle license plate, resolutely unified and standardized, resolutely eliminated the accumulated disadvantages, and significantly improved the standard level of license plate management.

　　The license plate issuance is fully fair and open;The nationwide promotion of motor vehicle number plate selection system, unified number plate distribution, unified number pool management, unified number supervision, put an end to human operation, all number plate numbers are distributed to the masses fairly and openly, and online number selection, "one out of 20 ~ 50" and other service measures are fully implemented, which are widely welcomed by the society.

　　Comprehensive popularization and application of new energy vehicle license plate;In December 2016, after the pilot projects in Shanghai, Nanjing, Wuxi, Jinan and Shenzhen were launched, in July this year, the special number plates for new energy vehicles were fully promoted and applied. Up to now, a total of 19 cities have launched special number plates for new energy vehicles, and a total of 150,000 new number plates have been issued.

　　Measures for the convenience and benefit of entry-exit service management

　　Keywords: foreigners’ permanent residence certificate, travel service measures, border inspection policies and measures.

　　First, it is more convenient for foreigners to apply for permanent residence certificates.

　　On June 16, the new version of the permanent residence identity card for foreigners was issued, and the permanent residence certificate for foreigners was machine-readable. Since the card was put into use, it has been issued smoothly and received good response, and all sectors of society have given positive comments. Up to now, 4,819 new permanent residence identity cards for foreigners have been signed and renewed.

　　Second, the service measures to facilitate the people to travel for permits continued to be introduced.

　　Provide convenience for people to apply for permits at home and 24-hour self-service, study and standardize the work of setting up acceptance windows for entry and exit documents in police stations, and set up acceptance points in 901 police stations in 15 provinces (autonomous regions and municipalities directly under the Central Government); Actively promote the policy of residence permit holders applying for entry and exit documents at their places of residence, and the implementation scope has been extended to 284 cities across the country.

　　At the same time, in order to actively promote the electronic reform of entry and exit documents, the electronic pass to and from Taiwan was fully launched on April 24 this year. All five types of entry and exit documents mainly for private purposes in China were electronically realized, and the holder’s self-service customs clearance was realized simultaneously, and the anti-counterfeiting performance of documents and the efficiency of issuing and checking were significantly improved. At present, the exit-entry administration departments of public security organs across the country have issued a total of 199 million electronic exit-entry certificates.

　　(The picture shows that the exit-entry administration department of the public security organ in Luohu District, Shenzhen, Guangdong Province has built a 24-hour self-service accreditation service area. )

　　Third, the border inspection policies and measures continue to be optimized.

　　Shanghai and other hub air ports have carried out convenient measures such as trial implementation of direct round-trip crew exemption from border inspection procedures and the opening of the "single window" platform for international trade by the national seaport border inspection authorities. Take Shanghai Hongqiao Airport as an example. Since the implementation of this policy on March 26th, Shanghai Border Inspection Station has handled the formalities of exemption from border inspection for the direct flight crew of eight airlines, providing convenience for the crew of 4102 flights with 55378 passengers.

　　At the same time, the self-service customs clearance service has also been vigorously promoted, and passengers with electronic travel permits "L" can now carry out self-service customs clearance. Since the beginning of this year, 912 self-service channels built at 62 travel inspection ports across the country have cleared 125 million inbound and outbound passengers, accounting for 42.8% of the total number of inbound and outbound personnel.

　　It is understood that the Ministry of Public Security and the China Insurance Regulatory Commission have deployed and promoted the work of quick compensation for road traffic accidents in highway and rural areas nationwide in order to solve the problems of long period and complicated procedures in handling and settling claims for road traffic accidents in rural areas, which has played an important role in improving the efficiency of accident handling, alleviating traffic congestion and avoiding secondary accidents.

　　In addition, the Ministry of Public Security has joined hands with China Post to carry out postal outlets to handle public security traffic control business, which has been successfully piloted in Wuxi, Jinhua and Chengdu. Zhejiang has deployed and promoted it throughout the province, effectively expanding the service network and extending the service tentacles, making it convenient for people to handle traffic control business nearby.

　　In terms of entry and exit management, the implementation of Beijing-Tianjin-Hebei regional linkage has also been promoted. Guangdong Province has implemented a 144-hour visa-free transit policy for foreigners, and Hainan has also implemented a visa-free entry policy for 59 countries.