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Author: insight ciyu

Let flowers become flowers and trees become trees.

After middle age, life seems to enter a difficult mode.

Open your eyes and be busy with trivial matters at home and difficult work, close your eyes and worry about the money in your pocket and bother your children’s studies.

40 years old is like a watershed.

You can’t be light any more, and the weight of life is hung on your body, and the years are in a mess.

But the bitterness of life, we can’t avoid it, we can only change the way of living.

Learn to start a minimalist life and manage the following three points, and life will not be too sad.

01

save money

When we were young, we pursued the idea that making money costs nothing and living is meaningless.

I didn’t understand until I was a certain age. If I don’t take money seriously, money won’t take you seriously.

Recently, after revisiting Friends, actor Joey immediately moved into a luxury apartment after becoming the main character.

The weekly salary is used by him to buy brand-name clothes, purses and jewelry.

Occasionally, he is short of cash, and he uses his fame to "brush his face" in the business.

A friend advised him that it was rare for his career to improve and he should seize this opportunity to save more money.

He didn’t agree: why do you have to live like a supporting role when you finally start playing the leading role?

Three months later, the crew cut Joey’s role because the ratings of the series declined.

Joey moved out of the luxury apartment, and the luxury goods he bought at a high price could only be sold at a low price.

When his friend saw him again, he was holding his stomach and auditioning painfully.

It turned out that Joey was infected with hernia shortly after he left the crew. Because he had no savings, he had to find a job first, and then he could reimburse the operation expenses through labor insurance.

From spending money like water to being short of money, Joey’s story verifies Munger’s words:

"The importance of saving money lies not in how happy you are when you have money, but in how embarrassed you are when you have no money."

How many middle-aged people don’t understand this truth

In order to lose face, when a friend buys a limousine, you have to bite your teeth and change it.

For the sake of so-called exquisiteness, you should choose all kinds of famous brands to wear, and you need tens of thousands of clothes.

Earning money is like picking dirt, spending money is like pushing sand with water, and our wallets will be flat if we are not careful.

Now, I agree with an old saying more and more: soup without salt is not as good as water, and people without money are not as good as ghosts.

When is the heart the most bitter? When you treat a disease, your pocket is cleaner than your face, and your heart is the most bitter at this time.

When is the most humiliating time? When you use money, you humbly ask for help everywhere, which is the most shameful.

The writer Li Ao told a story in Money is a Good Thing.

When Sima Guang was prime minister, people often came to visit him.

When he chats with people, the most common question he asks is: "Is your family rich?"

Many people are curious about why Sima Guang asked.

Sima guang explained: if you have no money, you can’t help but bend your back for five buckets of rice; Only when you have money can you have an independent personality. You can not be an official at any time.

Money can not only keep you from starving to death, but also protect your freedom.

How well it is said, money is an amulet, a ship crossing the sea of suffering.

The money to be spent, thousands of dollars and two thousand dollars; You should save every penny of money you shouldn’t spend.

When people reach middle age, everything will rest, and only money can solve their worries.

02

health maintenance

45-55 years old is an interesting age group.

We all say it is the golden age of life.

Doctors call it: the swamp of life journey.

At this age, the body began to decline, organs began to age, and various problems occurred frequently.

Zhihu netizen @ Liyong is a doctor of cardiovascular medicine. He received a 50-year-old uncle.

This uncle is a chain smoker.

He must have three or two glasses of white wine before eating these two meals at noon and evening. If it is a family gathering or a friend’s dinner, he has to drink until he is drunk.

Smoking is even more fierce, with three packs a day. When you are busy, you can have one to relieve your fatigue. When you are free, you can smoke and relax.

Long-term uncontrolled drinking and smoking have laid many hidden dangers for his health.

This winter, once he had a stroke and fainted at home because of excessive drinking. Fortunately, his family sent him to see a doctor in time before he picked up one.

Uncle couldn’t help dying.

In case someone else is really gone, will the whole family collapse?

If he is paralyzed by a stroke, will it drag down his children and partners?

Middle-aged people are the pillar of a family, so they can’t get sick or fall down.

When people reach middle age, it is time to be healthy, not only for themselves, but also for their families.

Here, I have two suggestions for keeping fit.

One is health, health first.

Drink less, smoke less, and plug the loopholes in health from the root.

Exercise more, pay more attention to diet and nutrition, and take good care of your body.

At the same time, insist on regular physical examination every year, track and review the problematic indicators in time, and sweep away hidden dangers.

The second is health care, and it is necessary to raise the heart.

There is a proper noun called "cancer personality".

Modern medicine found that long-term anxiety, fear, sadness and other emotions, these bad emotions will affect and reduce the body’s immunity with a chronic and sustained stimulus, and increase the incidence of cancer.

An inch wider than the heart, ten feet away from illness.

Forget what you should forget, let go, and you will be safe in your heart.

Philosophers have a famous saying: keeping healthy is the responsibility of being a man.

Taking care of your health is the responsibility of middle-aged people.

When we have a good health, we are qualified to protect our families and enjoy family happiness.

03

Bujiwa

For middle-aged parents, the difficulty of life is half the hardship of making a living and half the worry of children’s education.

Especially for the latter, education is a mountain on them.

A wrong question can make them crazy, and a failure in the exam will make them worry.

This should be a word from Professor Peng Kaiping: Education is one of the most anxious places in this society.

In recent years, the news that chickens are anxious is not uncommon.

For example, a boy in Shanxi was slapped by his mother because he was unfamiliar with the knowledge of chemistry.

A pair of 985 master’s parents were so angry with their son that they always had quick-acting rescue pills.

You see, in the end, the parents are exhausted and the parent-child relationship is in jeopardy.

Blogger @ 中中中中 works as a Chinese teacher in a key primary school.

After her son goes to primary school, she will make detailed study plans for her children every day and every week.

Apart from teaching at school, she devoted almost all her time to her children’s study.

In the evening, she will accompany him to finish his homework in various subjects, supervise him to preview and review, and correct problems as soon as they are found.

On weekends, she took her children around in various interest training classes.

Who would have thought that such a chick tortured the children and drove herself crazy.

The child is tired of learning because of the pressure she exerts.

She was angry when she saw the child’s poor learning state.

Mother and son unconsciously fell into a vicious circle of "she is in charge-the child won’t listen-she gets angry-the child loses his temper and doesn’t want to study".

She had to change the way of education: give her children a relaxed learning environment and stop interfering too much.

During that time, she focused on teaching when she was busy, reading books and arranging flowers to entertain her body and mind when she was free, and asked about her children’s learning once a week.

She finally found herself annoyed less often, and her children no longer rejected learning.

Blindly following the trend will only make children depressed and make themselves anxious.

Alison Gopnik, a child psychologist, divides parents into "gardeners" and "carpenters".

The former focuses on children’s habits without excessive intervention.

The latter focuses on their own standards and requirements and transforms children step by step.

Good parents are gardeners.

They only provide soil for children to grow freely.

Let flowers become flowers and trees become trees, which is to free children and fulfill themselves.

▽

Balzac said: In the stormy weather of life, we should learn from the captain and throw away the heavy cargo in the stormy weather to reduce the weight of the ship.

Once a man reaches middle age, he becomes a captain at the helm.

Looking at our life, one thing after another, one level after another, makes people have to rest.

But after careful combing, you will find that the most important things are nothing more than three things: money, health and children.

Halfway through life, learn to switch to minimalist mode.

When we can solve these three major events, we can actually solve our lives.

Original title: "Minimalist life of middle-aged people: saving money, preserving health and not having a baby"

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Recently, the Ministry of Finance, the Ministry of Industry and Information Technology, the Ministry of Science and Technology and the Development and Reform Commission (hereinafter referred to as the four ministries) jointly issued the Notice of the Development and Reform Commission of the Ministry of Industry and Information Technology of the Ministry of Finance on the Financial Subsidy Policy for the Promotion and Application of New Energy Vehicles in 2022 (Cai Jian [2021] No.466, hereinafter referred to as the Notice), which is now interpreted as follows:

First, about the background of the "Notice"

In accordance with the decision-making arrangements of the CPC Central Committee and the State Council, since 2009, the Ministry of Finance and relevant departments have strongly supported the development of new energy automobile industry. Thanks to the joint efforts of all parties, the technical level of new energy vehicles in China has been continuously improved, and the product performance has been significantly improved. The production and sales scale has ranked first in the world for six consecutive years.

In April 2020, the four ministries and commissions jointly issued the Notice on Improving the Financial Subsidy Policy for the Promotion and Application of New Energy Vehicles (Cai Jian [2020] No.86), which clarified that "in principle, the subsidy standards for 2020 -2022 will be reduced by 10%, 20% and 30% respectively on the basis of the previous year, and the vehicles that meet the requirements in the public transportation field will not be reduced in 2020. In 2021, the new energy automobile industry still achieved substantial growth in the face of adverse effects such as global epidemic spread and chip shortage, and the industrial development trend was good. In 2022, the subsidy policy will continue to decline in an orderly manner according to the established arrangements, creating a stable policy environment. The four ministries and commissions jointly issued the Notice in the near future, clarifying the relevant requirements of the financial subsidy policy.

Two, about the new energy vehicle purchase subsidy standard in 2022

According to document No.86 [2020] of Caijian, the subsidy standard for purchasing new energy vehicles in 2022 will be reduced by 30% on the basis of 2021; For new energy vehicles that meet the requirements in urban public transport, road passenger transport, rental (including online car rental), sanitation, urban logistics and distribution, postal express delivery, civil aviation airports and official fields of party and government organs, the subsidy standard in 2022 will be reduced by 20% on the basis of 2021. According to this, the "Notice" clarifies the subsidy standards for different types and different fields of vehicle products, and will be implemented as of January 1, 2022.

III. Requirements for technical indicators of new energy vehicle products in 2022

In recent years, under the guidance of subsidy policy, the supply quality of new energy automobile products in China has been continuously improved, the technical level has been significantly improved, and the practicality of products has been greatly improved. According to document No.86 [2020] of Caijian, "In principle, the technical indicators will be generally stable in 2021-2022", the purchase subsidy policy in 2022 will keep the thresholds of technical indicators such as energy density, driving range and energy consumption of the power battery system unchanged, and stabilize enterprise expectations.

Four, on the clear purchase subsidy deadline node

According to the requirements of Caijian [2020] No.86 document, the implementation period of financial subsidy policy for the promotion and application of new energy vehicles will be extended to the end of 2022, taking into account factors such as technological progress and scale effect. Considering the development plan of new energy automobile industry, market sales trend and the smooth transition of enterprises, in order to maintain the good development momentum of new energy automobile industry and stabilize the expectations of the industry and consumers, the Notice clarifies that the subsidy policy for new energy automobile purchase will be terminated on December 31, 2022, and vehicles that are licensed after December 31 will no longer be subsidized.

V. On Further Strengthening Product Safety Supervision

The safety of new energy automobile products concerns the vital interests of consumers and is an important guarantee for the healthy and orderly development of new energy automobile industry. In recent years, new energy vehicle products with intelligent networking characteristics have been gradually applied to the market, and the problems such as data security and network security have become important concerns. Fires and safety accidents of new energy vehicles still occur from time to time in China. In order to further strengthen product safety supervision, ensure vehicle quality and information safety, and effectively protect the interests of consumers, the Notice clearly puts forward measures such as improving the safety supervision system of new energy vehicles and further compacting the main responsibilities of new energy vehicle manufacturers. At the same time, an inter-departmental information sharing mechanism and a vehicle accident reporting system will be established around vehicle fires, major accidents, etc. For enterprises that conceal accidents and do not cooperate with the investigation, the vehicle subsidy qualification will be suspended or cancelled according to the seriousness of the case.

Original Socrates’ afternoon tea medical rheumatism immunity channel

* For medical professionals only.

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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