New thinking in the age of great health

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Human beings have entered an aging society, and they are facing the threat of chronic diseases while living a long life. Unlike infectious diseases caused by foreign pathogens, chronic diseases are c

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    Human beings have entered an aging society, and they are facing the threat of chronic diseases while living a long life. Unlike infectious diseases caused by foreign pathogens, chronic diseases are caused by problems in the body, and the causes are complex and changeable. More troubling, chronic diseases show marked differences between individuals, even within individuals. Therefore, we should not simply "see a doctor", but "see a person". Chronic diseases take time to develop, usually from a state of health to a state of illness.               Therefore, it is necessary to use the "window period" before the onset of disease to move the "threshold" of disease resistance, early monitoring and early intervention, and implement health management and maintenance of the whole life cycle.
    Two aspects of an aging society: "longevity" and "chronic diseases"
Mankind has entered an aging society. Since the 20th century, life expectancy has increased significantly in developed countries such as the United States and Japan, and the trend will continue. In this sense, people have greatly improved their ability to control and maintain their own health.     Longevity is one of the core goals of human pursuit. China has been pursuing immortality since the time of emperor qin shihuang. Real or virtual, it reflects a desire to live longer in the world. In the 30 years of reform and opening up, China has achieved the success that western developed countries have achieved after more than 100 years of efforts, and entered an aging society in an all-round way. A 2015 United Nations report predicted that China's population would surpass that of the United States by 2035.
    Longevity is a sign of progress in a country. In government work reports in recent years, it is common to mention that life expectancy has increased again. The increase in life expectancy per person is an important indicator in the health China 2030 agenda: from 76 in 2015 to 79 in 2030. However, most things in the world tend to have two sides. Living longer is the good side, but it is also accompanied by an increase in chronic noncommunicable diseases (chronic diseases). According to a world bank report on aging at the end of 2015, longevity and prosperity: aging societies in east Asia and the Pacific, 36% of the world's over-65s now live in northeast Asia. By 2030, cancer, heart disease, diabetes, alzheimer's and other age-related chronic diseases are expected to account for 85 percent of all illnesses in the region. In the past, most of the diseases that caused human death were infectious diseases.         Today chronic diseases have replaced infectious diseases as the leading cause of human death.
Chronic diseases are not only harmful to personal health, but also to society. Chronic diseases usually require long-term treatment, which is a heavy financial burden for the whole society and for every family. According to statistics, China spent more than 300 billion yuan on alzheimer's disease in 2015. It costs money to see a doctor and more money to treat chronic diseases. The world health organization estimates that the cost of alzheimer's disease worldwide will exceed $1 trillion by 2018 and $2 trillion by 2030. This shows that chronic diseases are a great economic pressure on society and individuals.
    Why is living long associated with chronic diseases? The main risk factor for chronic diseases is age: the older you are, the higher your risk of them. For example, neurodegenerative diseases are associated with cognitive decline. According to a statistical study by Chinese and American scientists, the cognitive abilities of middle-aged and old people in China show a linear decline with the increase of age, regardless of men and women [1]. All in all, chronic diseases such as cancer, diabetes, cardiovascular and cerebrovascular diseases and alzheimer's disease are more likely to occur with age.
    For thousands of years in civilized society, the main threat to human health has been infectious diseases. Bubonic plague, known as the black death, was a severe epidemic in the middle ages. In just three short years in the middle of the 14th century, nearly 30 million people in Europe were killed by the black death. The number of deaths from smallpox was also significant; According to statistics, the total number of European deaths from smallpox in the whole of the 18th century was more than 150 million. With the continuous progress of science and medicine, human's ability to fight against infectious diseases is also improving. As far as fighting trichoderma is concerned, everyone knows that the most effective way is to grow vaccinia. As early as the 16th century, there has been a literature on vaccination in China. After British doctor Edward jenner discovered vaccinia in the 1770s, British researchers perfected the vaccine and applied it to the prevention of the disease. Because of the success of these anti-infectious technologies, people can even eliminate an infectious disease from the earth. On October 26, 1979, the world health organization (who) announced in Nairobi, Kenya's capital, that human smallpox had been eradicated and that October 25 every year was designated as "human smallpox eradication day".
    Because the past has been so successful in fighting infectious diseases, it is sometimes assumed that chronic diseases can be eliminated like infectious diseases, and that the threat of chronic diseases can be eliminated completely. Every now and then we read in the press about the elimination of tumors or certain chronic diseases; For example, former U.S. President barack Obama announced in congress in January 2016 that the government would launch a "lunar mission" to eliminate cancer, with the goal of "Let's make America the countrythat cures cancer once and for all." So can we eliminate chronic diseases like cancer and diabetes as well as infectious diseases?
    We must recognize the essential difference between chronic diseases and infectious diseases. Infectious diseases are invariably caused by attacks on humans by foreign organisms, such as smallpox or yersinia pestis. So, we can eliminate these exogenous pathogens completely. However, diseases such as cancer, obesity and alzheimer's are all internal problems.         Tumors are caused by mutations in one or more cells in the body, obesity by problems in the tissues or organs responsible for regulating energy metabolism, and alzheimer's by the death of brain nerve cells. Therefore, we cannot eliminate chronic diseases from the earth like infectious diseases.
    We can think of the body as a car with about 400,000 billion cells, each of which has thousands of different types of genes and proteins. Apparently, the longer the body USES the car, the more likely its cells, genes, proteins and other components are to go wrong. Why weren't chronic diseases as bad as they are today? Because of the bad road conditions in the past -- there were germs everywhere -- the car was knocked over by an epidemic before long. Now the car is running on the road in good condition, and it will not turn over if it drives 80,000 or 100,000 kilometers. As a result, it is obvious that various problems will occur in the body parts of this "car" due to its long use. Obviously, even if science and technology or medicine are developed in the future, age, the most important risk factor for chronic diseases, cannot be eliminated. It should be emphasized that "longevity" is still the main goal of human beings. Therefore, faced with the challenge of chronic diseases and the challenge of infectious diseases, our response measures should be different.
    Evolution of disease view: from "seeing a doctor" to "seeing a person"
In the era of fighting infectious diseases, the primary task is to determine the etiology. An infectious disease must correspond to a specific pathogen. For example, while smallpox was the source of trichoderma, bubonic plague was caused by yersinia pestis. In other words, the causes of infectious diseases are usually single and definite. Therefore, the modern medical "disease view" has been formed: the occurrence of diseases has a definite reason, and the same diseases have the same etiology. Obviously, according to such a disease view, the difference between patients is not important, it needs to focus on the disease itself rather than the individual patient.
"Evidence-based medicine" is the main medical model for chronic diseases, and its theoretical basis is the non-individualized disease view. Evidence-based medicine emphasizes that the basis of diagnosis and treatment of diseases is a clinical guide with scientific evidence. This scientific evidence is mainly from "Randomized controlled trial". This term may sound complicated, but it's actually quite simple to understand. The first is to have a lot of trial samples, for example, to test the efficacy of a drug, you need to find hundreds of thousands of patients to participate in the trial. Second, the individual differences among these patients should be eliminated as far as possible, that is, the subjects should be selected as consistent as possible according to specific criteria, and the subjects should be randomly assigned to the experimental group and the control group. Such a study could be used to test the probability of therapeutic effects. For example, if there are 90 people who respond to a drug, the efficacy of the drug is very high. If only 10 of the 100 patients responded to the drug, it would not work well. Therefore, evidence-based medicine is a typical non-individualized medicine, which focuses on the characteristics of the disease itself rather than the individual differences between patients.
    Although evidence-based medicine as the mainstream of modern medicine, plays an important role in the current fight against chronic disease, but its statistical characteristics of the obvious problem of "the accuracy", published in April 2015, according to an article in the journal nature in the UK, points out that in drug sales income of the top ten in the U.S. are used in the treatment of chronic diseases, but their effectiveness is not high, only three kinds of drug efficiency reached 25%, the rest of the seven kinds of efficient is low; For example, a drug commonly used to treat hypercholesterolemia, rosuvastatin, is only 5 percent effective, meaning that only one in 20 people taking it is effective [2]. In other words, although randomized controlled trials can find the maximum probability that a drug or treatment regimen will be effective for a given condition, it doesn't guarantee that the drug will actually be effective when applied to a specific patient. On the contrary, for every specific patient, the medicine that always wants to be taken is completely effective.
    Why does modern medicine face this kind of non-precision problem in the face of chronic diseases? Because chronic diseases are very complicated diseases. First of all, from the perspective of etiology, it usually involves not only one factor, but many internal physical factors and external environmental factors, as well as the interaction between these internal and external factors. Cancer, for example, is caused by a large number of genetic mutations. Not long ago, researchers analyzed more than 7,000 samples from 30 different types of tumors through advanced sequencing technology, and found a total of nearly 5 million individual cell mutations, with an average of more than 160,000 sequence mutations per tumor [3]. At the same time, the environment plays an important role in the formation of tumors. For example, smoking cigarettes can induce gene mutation, which can significantly promote the occurrence of lung cancer. Excessive sun exposure often leads to skin cancer. It has been pointed out that external environmental factors play a more important role in the occurrence of many types of tumors than internal factors such as gene mutation [4]. Obviously, the complexity of this etiology leads to different pathogenesis of the same type of disease.
    It has been well recognized that there are significant individual differences between patients with chronic diseases, and that performance and response to drugs are often different among individuals with the same disease, even if they have the same disease. On the one hand, it may be caused by different pathogenesis between individuals, on the other hand, it can be attributed to different genetic backgrounds and different living environments among individuals. And, more importantly, the researchers found that now, diseases such as tumor has not only difference between individuals (Intertumour heterogeneity), and also has the obvious individual differences within (Intratumour heterogeneity). For example, through single-cell sequencing technology, it is found that the genetic variation of different tumor cells is different in the same patient's breast cancer tumor [5]. It's a hassle. A drug can only kill tumor cells that are sensitive to it, not non-sensitive tumor cells. For example, there is a targeted drug for lung cancer called gefitinib that targets a specific mutation in a particular gene in a lung cancer cell. The drug works so well that any cell with the mutation can be killed. But doctors know that after three months, the medicine often doesn't work. This is because there are still tumor cells in the body that do not have this mutation, and they are not sensitive to the drug, and over time the tumor regrows.
    To address the inaccuracy of evidence-based Medicine in the fight against chronic diseases, a new international model, Precise Medicine, has emerged. In 2011, the American academy of sciences released a strategic report on how medicine should develop in the future, "towards precision medicine -- building a knowledge network of biomedical research and a new classification of diseases" [6]. The word "march toward" clearly describes the current state of medicine and the future direction of medicine. Second, future medicine will have to be "precise".
    Accurate medicine core is to "individual as the center", to complete access to the individual from the genome and proteome molecular level to the physiological and pathological character, intestinal flora of phenotypic level data, and the environment behavior and the macro level data, used to construct individual disease knowledge network, and on this basis to realize the individual health maintenance and precise diagnosis and treatment. Although the concept and theory of precision medicine remain to be improved, it is clear that precision medicine is a typical individualized medicine. In the face of complex chronic diseases, we should not simply "see a doctor" as we do in the face of infectious diseases, but "see a person" from the perspective of the complexity of the body and the disease.


    Here's an example of dietary control to help you understand the precise medical research strategy. People with obesity and diabetes need specific dietary controls in addition to medication. It used to be believed that different foods had different effects on the changes of blood glucose concentration in the body after a meal, but the same food had the same effect on blood glucose in different individuals. Therefore, doctors do not pay attention to patients when guiding diet control The differences between individuals are primarily about the differences between foods, such as not eating foods that significantly increase blood sugar. Not long ago, the Israeli scientists on 800 volunteers in 46000 measured blood glucose change after meals, at the same time also collected these subjects information such as the intestinal flora and way of life, then has carried on the statistical analysis of these data, to find the same kind of food in blood sugar effect between people, in fact, there is a very big difference [7]. Therefore, it can be expected that sometimes the blood glucose control of a diabetic patient is not up to the standard, maybe it is not the insufficient implementation of the diet control requirements of the doctor, but the individual differences lead to the doctor's diet control requirements not getting the expected response. Ideally, find individual differences in diet, and then propose individualized diet control plans for specific individual differences.
    Key words in health: from "disease" to "health"
China has entered an era of great health. In 2016, the Chinese government convened the first national health and health conference, at which it proposed the goal of building a healthy China -- providing health and health services for the whole life cycle of the people. It is important to note that the term "whole life cycle" was coined to mean that the task of safeguarding people's health is no longer the same as in the past, with health services focused on the diagnosis and treatment of diseases. The new view is made clearer in the national health China 2030 planning outline: "accelerate the transformation of the development mode in the health sector, maintain and safeguard people's health in all directions and throughout the whole cycle", and "achieve health services and health protection from the fetus to the end of life".
The key to this shift is to move the disease barrier forward and make health a priority. This fully reflected in the program for the health of China's 2030 first put forward by the principle: "put health on the priority development of strategic position, based on national conditions, to promote the concept of health into the whole process of public policy implementation, speed up the formation of healthy way of life, ecological environment and the economic and social development pattern, realize the benign coordinate health and economic and social development".
    Arguably, the shift is mainly for chronic diseases. One of the main differences between chronic diseases and infectious diseases is that infectious diseases usually start quickly, while chronic diseases take a long time to occur. Taking the occurrence of type 2 diabetes as an example, the body usually moves from the normal glucose metabolism stage to a sub-healthy stage of decreased insulin sensitivity, which is called insulin resistance. At this time, the body can still compensate by increasing insulin secretion, without showing clinical symptoms. If the body loses its ability to compensate, it enters a high-risk period called pre-diabetes, when blood sugar levels rise to a tipping point. If this metabolic abnormality develops further, the body will enter the clinical stage of diabetes. A survey report on diabetes epidemic released by Chinese researchers in 2013 indicates that the number of diabetes patients in China is about 100 million, while the number of people at high risk of pre-diabetes is nearly 500 million [8].
    It can be seen that the formation of chronic diseases is a process of gradual transformation from a healthy state to a disease state. Before the appearance of clinical symptoms, various transition states, such as sub-health state or pre-disease state, will appear first. Clearly, such a pre-onset sub-health "window period" offers an important opportunity to combat chronic diseases. People should not wait for diseases to appear before they are diagnosed and treated as in the past. For example, we should move the diabetes threshold up to 500 million people at high risk of pre-diabetes, monitor them early and intervene early, slow them down to the clinical stage of diabetes, and even bring them back to normal from the early stage of the disease. In the case of cars, for example, if you regularly maintain your car during use, the time of major problems will be delayed. On the contrary, if it is not maintained in time and only used blindly, it will break down quickly. There is a classic saying in traditional Chinese medicine, "go up to cure no disease", that is, the wise doctor has been aware of the disease before it occurs, and is about to intervene. This conventional view is very much in line with today's idea of moving the disease barrier forward.
    Moving forward against chronic diseases is not only the best policy from the perspective of disease prevention, but also the best policy from the perspective of social economy. Once most chronic diseases enter the clinical stage, they are often difficult to cure and require lifelong medication. What's more, the prognosis of these chronic diseases is often poor, the development period or complications are harmful, and the rate of death and disability is high in the later stage of the disease. As a result, the treatment of chronic diseases is often "cost-effective", with more investment and less benefit. The "move forward" strategy can significantly improve the "cost-effectiveness" of the fight against chronic diseases. A popular belief is that a dollar spent by the government and society on chronic disease prevention is equivalent to six dollars spent on treatment.
    From an individual's point of view, the same conclusion can be reached. Take enjoying life as an "output", take healthy maintenance as an "input", and make an analysis of the "input output ratio" : when we are in a healthy state, we do not have much investment in maintaining health and can enjoy life to the fullest, so the "input output ratio" is very ideal. Once suffering from chronic diseases, such as diabetes, the investment in maintaining health is significantly increased. Patients need to go to the doctor and take medicine. If the disease continues to develop, such as diabetes complications, more money will be spent on treatment, and the quality of life will become worse. The "input-output ratio" in terms of individual health could conceivably be worse. Therefore, it is more economic and reasonable for the country and society, as well as for families and individuals, to move the "battlefield" against chronic diseases beyond hospitals.
    The U.S. government is proposed to carry out accurate medicine in 2015, the main content is to start a cohort study on 1 million volunteers in the United States, plans to turn these individuals within the period of 10 years or so of biomedical data are collected, analysis process and their physiological and pathological change, thus for health management and provide guidance to fight against chronic diseases. The main goal of the precision medicine program proposed by the americans is not to care about how diseases are diagnosed and treated, but to focus on how individuals evolve from healthy to sick. Thus it can be seen that the main goal of precision medicine initiated by americans is to move the barrier against chronic diseases forward. The us national institutes of health published a detailed plan on the 1m us volunteer Cohort study in September 2015, called the Precise Medicine Initiative Cohort Program. It is worth noting that a year later, the nih decided to change the name of the Program to "All of Us Research Program" to further emphasize the "great health" features of the Program.
    For more than two thousand years, human society has established typical clinical medicine on the basis of combating infectious diseases. People have formed a "disease-centered" thinking habit, "curing diseases and saving people" is the primary task of medicine. It can be said that "disease" is the key word in this era of clinical medicine. Around the "disease", various diagnostic techniques have been developed, from simple stethoscopes to sophisticated imaging machines, as well as various treatments such as surgery, vaccines and drugs. Hospitals and other places for patients' diagnosis and treatment were established, and a medical insurance system was created to help patients and society pay for the treatment of diseases.
    In the 21st century, mankind has entered a new era of great health. The main threats to human health have shifted from infectious diseases to chronic diseases. "moving forward" and "health first" are more reasonable and economical strategies to combat chronic diseases. Therefore, in such a new era of health medicine, the key word should be changed to "health". Around the "health", we need to develop to the body's new technique for early detection of pathological changes, develop to maintain health and prevent disease early intervention method, set up for the whole life cycle of the individual community health management system, create a capable of supporting the whole society and the individual demand for health maintenance costs of health care system.