As far as the current research status is concerned, the pathogenesis of ulcerative colon cancer is still unclear, but the main causes of UC are heredity and environment, intestinal wall infection, and then intestinal flora imbalance and abnormal immune regulation, in which the immune regulation of long mucosa is the main reason, and colon, intestinal mucosa and submucosa are one of the main links in the pathogenesis of ulcerative colitis. Because long mucosa belongs to the protective mechanism of colon and has the physiological function of immune barrier, these barrier functions support each other to ensure the normal operation of colon mucosa function, so as not to damage colon. Therefore, the injury of intestinal mucosa is more likely to lead to intestinal infection and abnormal immune response. At the same time, it is found that intestinal microecological imbalance plays an important role in the pathogenesis of ulcerative colitis. In addition, some studies have found that ulcerative colon is also closely related to mental factors.
At present, the 20 17 Opinions on the Treatment of Inflammatory Bowel Disease in Ulcerative Colitis published in China clearly points out that the treatment of ulcerative colitis should first master the principles of classification, staging and treatment by stages. However, with the in-depth study of the pathogenesis of ulcerative colitis, the current treatment methods have been diversified. At the same time, the choice of treatment methods emphasizes the individualization and standardization of treatment schemes. At present, the main treatment methods of ulcerative colitis are: traditional drug therapy, fecal flora transplantation, white blood cell separation, hyperbaric oxygen therapy and so on.
2. Pathogenesis of ulcerative colitis.
At present, a large number of studies believe that the pathogenesis of ulcerative colitis may be: under the influence of environmental factors, with the participation of antigens such as intestinal flora or food, genetic susceptibility starts the intestinal immune system, leading to intestinal over-immunity. And eventually lead to the destruction of intestinal mucosal barrier. Mucosal injury will inevitably lead to pathogenic bacteria and toxins entering the intestine through the mucosal barrier; Entering the portal vein system and lymphatic system induces immune response and develops into ulcerative colitis and other diseases. By consulting a large number of documents, the author summarizes the mechanisms of immune abnormality and intestinal mucosal barrier destruction caused by various factors as follows:
1. Genetic factors
Now the research on ulcerative colitis is hereditary. For example, foreign scholars found that 10. 1% of 454 UC patients had family history. The incidence of white people in Europe and North America is higher, while the incidence of yellow people in Asia is relatively low. This shows that the incidence of UC is related to race, and UC is mainly inherited by genes. It has also been found that miRNA (MicroRNA) plays an important role in the pathogenesis of UC, because its gene can affect the abnormal apoptosis of intestinal epithelial cells, destroy the integrity of intestinal mucosa and intestinal barrier, and lead to increased inflammatory response.
2. Environmental factors
Judging from the current research results, the pathogenesis of ulcerative colon cancer largely lies in the patient's eating habits and living environment. If the patient's long mucosa is damaged because of his eating habits or living environment, it will induce abnormal intestinal immunity and abnormal intestinal flora. At present, these factors are mainly diet, use of antibiotics and non-steroidal anti-inflammatory drugs, stress and infection. For example, some scholars found that meat, eggs and protein-rich foods have a relatively high impact on the risk of ulcerative colitis and the success rate of surgery, but there is no relevant research on the impact of such factors on colitis. Generally speaking, these factors mainly change the integrity of mucosal barrier, abnormal activation of immune response and imbalance of intestinal flora.
Intestinal mucosal barrier is mainly composed of basement membrane, epithelial cell layer and mucus layer on its surface. It can prevent harmful substances such as bacteria and antigens from entering intestinal mucosa, thus avoiding abnormal immune response of innate immune cells. According to the specific functional classification and mucosa can be divided into mechanical, chemical, immune and biological barriers. If the patient's own living habits or living environment lead to serious damage to the long mucosa and submucosa, the patient's long mucosal barrier will also change accordingly, resulting in damage to the intestinal barrier. In addition, low immune function will lead to enterogenous infection, which will lead to the decrease of immunoglobulin content and form a vicious circle.
The main cause of ulcerative colon cancer is immune abnormality of long mucosa, and the cause of mucosal abnormality is mainly immune cells and cytokines secreted by them. It is considered that the level of anti-inflammatory cytokines in intestinal mucosa of UC patients is decreased, while the level of pro-inflammatory cytokines is increased, resulting in imbalance of immune regulation. In addition, the pathogenesis of UC is also related to immune cells such as dendritic cells, and the dysfunction of macrophages may promote the development of intestinal inflammatory response.
3. Microorganisms
There are a large number of bacteria in human intestine, mainly including dominant bacteria (such as Bifidobacterium, Lactobacillus, Enterobacter, fecal bacteria, etc. ) and conditional pathogens (such as Enterobacter and Enterococcus). These bacteria constitute the intestinal microecosystem, which has the function of nonspecific defense and maintenance of intestinal physiological function. At present, most scholars believe that the imbalance of intestinal flora is closely related to the abnormal reproduction of related pathogens, which leads to the inflammatory reaction of intestinal mucosa, further causing immune abnormalities and eventually developing into colitis. Relevant scholars' research shows that compared with normal people, intestinal bacteria in patients with ulcerative colon cancer have an obvious growth trend.
4. Mental factors
Clinically, some patients with ulcerative colitis have many symptoms, mainly including nervousness, anxiety, doubt and hyperhidrosis. These mental symptoms may induce or lead to the further deterioration of ulcerative colitis. In addition, some scholars have found that patients with IBD have autonomic nerve dysfunction, and mental factors can obviously lead to autonomic nerve diseases.
5. Infection factors
The classification of intestinal infection can be roughly divided into two categories: one is intestinal flora infection, and the other is the pathogenesis of viral infection, which is mainly caused by Bacillus and Helicobacter pylori, while viral infection is mainly caused by viruses such as herpes virus and parvovirus. At present, it is generally believed that infection plays a role in the pathogenesis of UC, but so far, no infectious factors closely related to UC have been isolated. It is found that Clostridium and Bacteroides are closely related to the onset and aggravation of UC patients, and the contents of Clostridium and bacteria in the intestine of patients in active stage are obviously increased. At the same time, there are a large number of bacteria in normal human intestine, among which peptidoglycan nucleic acid and its derivatives are a kind of bacteria that mainly induce the development of ulcerative colon cancer, and their derivatives are receptor complexes that mainly move with colon epithelium. Recent studies (43-4) also show that UC is related to Helicobacter pylori, hepatitis B virus and cytomegalovirus.
3. Progress in surgical treatment of ulcerative colon
According to the above literature, the author found that the pathogenesis of ulcerative colitis is not only related to heredity, but also the intestinal immune regulation and shortage imbalance induced by the external environment will cause certain damage to the intestinal mucosa, and the microorganisms and related viruses in the intestine will also affect the abnormality caused by the repair of the long mucosal barrier, thus inducing ulcerative colon cancer and other related diseases. In recent years, scientists have conducted further research on the treatment of ulcerative colon cancer, including drug therapy, fecal bacteria transplantation, hyperbaric oxygen therapy, interventional therapy, leukocyte separation, stem cell therapy, traditional Chinese medicine treatment and surgical treatment.
3. 1 drug therapy
Because the pathogenesis of UC is still unclear, 5-aminosalicylic acid drugs, glucocorticoids and immunosuppressants are the main drug treatment schemes, supplemented by other drugs according to the condition. According to the guidelines for UC diagnosis and treatment, it is suggested to choose different types of drugs mentioned above, and adopt different ways of administration according to the severity and scope of the disease.
aminosalicylic acid
1, sulfasalazine
Sulfasalazine (SASP) is a classic drug of UC. Its mechanism of action is to inhibit the metabolism of arachidonic acid, thus inhibiting the downstream inflammatory factors and playing an anti-inflammatory role. It has no therapeutic effect, but it can be decomposed into salicylic acid and sulfapyridine in the intestine of patients with ulcerative colon cancer, and the specific remission rate can reach 80% or even higher, which is mainly used for mild and severe ulcerative colon cancer. Because the drug is relatively cheap, it has obvious therapeutic effect on mild and severe patients, and has great advantages in the treatment of remission, but there will also be adverse reactions in clinical use.
(1) Special preparation for 5-aminosalicylic acid (5-ASA)
Mesalazine (5-ASA) is a sulfasalazine (SASP) used to treat ulcerative colitis. However, most 5-aminosalicylic acid (5- ASA) is absorbed through the small intestine, so common dosage forms will affect its curative effect. Therefore, in order to achieve better therapeutic effect and reduce adverse drug reactions, a new 5-ASA preparation was developed on the basis of SASP, which mainly includes: slow-release or controlled-release dosage forms represented by Shar Fu. After oral administration, the pH value is released under the ileum.
Oshara has special physical and chemical properties, which makes it relatively stable in the stomach and small intestine. After reaching the colon, it was separated by bacteria in the colon and released 5-ASA, which played an anti-inflammatory role in the colon, thus reducing the irritation to the stomach and small intestine and reducing the adverse reactions of the gastrointestinal tract. Mesalazine exists in the form of granules and high concentration mesalazine, which can slow down the drug release, reduce the number of taking drugs and improve the compliance of patients. For example, Tan Yue found that 5-ASA oral preparation combined with enema is superior to oral preparation alone in the treatment of UC with non-severe multiple lesions. Although 5-ASA can significantly reduce adverse drug reactions, there are still occasional adverse reactions, such as nausea, vomiting, kidney damage, reversible male infertility, granulocytopenia, autoimmune hemolysis, aplastic anemia, myocarditis and so on. Therefore, blood routine, monitoring function and myocardial enzyme spectrum are needed when liver and kidney are administered.
(2) Glucocorticoid drugs
As far as the current research situation is concerned, glucocorticoid is the main cause of ulcerative colon cancer, which can inhibit the immune response of human body, lead to the decline of resistance to promote the growth and reproduction of some flora, and then lead to the onset of ulcerative colon cancer. Therefore, glucocorticoid should be strictly controlled in the process of strict treatment of ulcerative colon cancer, but in order to overcome some traditional drugs, the dose and direction of adverse reactions of glucocorticoid to patients need further study. Some scholars have found that beclomethasone dipropionate can effectively treat colitis and reduce adverse reactions. In addition, because of the side effects of glucocorticoid, it is not used for maintenance treatment of ulcerative colitis.
(3) Immunosuppressants
At present, a large number of literatures believe that the main pathogenesis of ulcerative colitis is the excessive and sustained development of intestinal immune response, which eventually leads to the destruction of intestinal mucosal barrier. Therefore, it can only be used for hormone-dependent or ineffective treatment, and can also be used for maintenance treatment after hormone-induced remission. 20 15 the new knowledge of inflammatory bowel disease group of gastroenterology branch of Chinese medical association suggested that if enough intravenous corticosteroids were used for five consecutive days without any effect, the combination of immunosuppressants should be considered, and cyclosporine A(CS a) was recommended. Because cyclosporine A takes effect quickly, generally less than 1 week. However, when using this drug, blood routine examination should be carried out within a certain period of time. In addition, azathioprine is also one of the immunosuppressants in the treatment of ulcerative colitis, but its action cycle is long, from12 to16 weeks, which is of little significance to clinical treatment. Hui Ding, a scholar from Jiang Kun, analyzed the adverse reactions of A J A in treating ulcerative colitis, and concluded that patients with rheumatoid arthritis would get worse after receiving azathioprine. Therefore, azathioprine is not recommended to induce and relieve ulcerative colitis in clinic and guidelines.
(4) Biological agents
It was found that TNF-α was related to ulcerative colitis. Biological agents play a role by inhibiting the key factors in the immune response pathway. At present, the commonly used biochemical reagents include human anti-TNF monoclonal antibodies, such as infliximab, adalimumab and new cytokine inhibitors. Infoxim can accelerate mucosal repair of intestinal injury and reduce hormone dosage. Such as splendor and so on. 12 week treatment of moderate and moderate ulcerative colon cancer can be divided into 60%, 80% and 90% at the 22nd and 38th week of the 6th week, respectively. Liu Jing, a related scholar, made a study with the English name treatment, and observed the recovery of long mucosa in 29 patients with severe ulcerative colon cancer within 6 weeks after operation, and found that the compound rate was 48%. However, infliximine has adverse reactions, such as infection, autoimmune reaction and local reaction, so it is not recommended for routine clinical use. Adalimumab has the same therapeutic mechanism as infliximab, but has few adverse reactions, so it has become the main drug to replace infliximab. For example, adalimumab was recruited to treat UC in Zhou. Compared with the control group, amino acid salicylic acid or hormone therapy was more effective. At present, due to the high price and potential risk of biological agents, there are few biological agents used in clinical practice in China.
(5) microecological preparation
According to the current research, it can be found that the pathogenesis of patients with ulcerative colon cancer is the long-term damage of mucosal barrier and the confusion of its flora. Probiotics and their derivatives can usually be found in clinic, which shows that the treatment of probiotics is very important for the strict treatment of ulcerative colon cancer. Gu Jiwei and others used Bifidobacterium to treat 120 UC patients, and the effect was good. It can be predicted that microecological agents more suitable for China people will continue to be used in clinic in the future.
3.2 fecal bacterial transplantation therapy
At present, it is believed that there are a large number of microbial values in human intestine, which constitute the biological barrier of intestinal mucosa. Intestinal flora imbalance is mainly manifested in the reduction of probiotics and the reproduction of pathogenic microorganisms. In this case, fecal transplantation therapy, which can maintain the stable structure of intestinal flora and restore the microbial environment of digestive system, has become a hot spot in the treatment of this disease. In the intestine, the normal intestinal flora is reconstructed, so as to achieve the purpose of treating intestinal and parenteral diseases. Fecal transplantation therapy can be traced back to the Eastern Jin Dynasty. The treatment of patients with FMT UC started from 1989, and the treatment effect was good. In addition, 75 patients with moderate UC, such as moayyedi, received fecal transplantation, and the clinical remission rate in the experimental group was 24%. Therefore, FMT is more effective and safe for patients with ulcerative colitis.
Although most literature reports that fecal bacterial transplantation has a good effect on UC, there are still many problems to be solved in clinical application of FMT. For example, the patient's psychological acceptance, the choice of donors, the best transplant dosage, the process of collecting feces, the best transplant time, time and cycle, the preparation of fecal bacteria, the best transplant method and so on. It has been shown that FMT through colonoscopy seems to be more effective than FMT through oral capsules.
3.3 Hyperbaric oxygen therapy
Hyperbaric oxygen therapy is a method to treat diseases by breathing pure oxygen or high concentration oxygen in high pressure environment. The main mechanism of hyperbaric oxygen in treating ulcerative colitis is as follows: 1. Increasing the oxygen concentration in the blood vessels of intestinal mucosa and improving the oxygen supply and metabolism of intestinal mucosa are beneficial to the repair of intestinal mucosa; 2, interfere with bacterial reproduction, play an anti-infection role and prevent further infection. In addition, it can also inhibit cellular immune response and mucosal inflammatory response. Therefore, hyperbaric oxygen is effective and safe in treating ulcerative colitis.
3.4 Hematopoietic Stem Cell Therapy
At the same time, cells with regenerative ability are hematopoietic stem cells. Patients with ulcerative colon cancer are a disease that will affect their own immune system. The main reason is the disorder of immune tolerance system. Therefore, in theory, transplantation of hematopoietic stem cells into patients' intestines and stomach can effectively treat U C and repair intestinal mucosa. The function of colonic mucosal stem cells in patients with ulcerative colitis is inhibited, which will affect the repair of colonic mucosa and lead to delayed inflammation. After hematopoietic stem cell transplantation, intestinal mucosa can be repaired. Therefore, stem cell therapy for UC has shown broad prospects, but a large number of samples are still needed to further study its effectiveness.
3.5 Interventional therapy
Through right femoral artery puncture intubation, superselective drug delivery catheter at the treatment site and injection of anti-inflammatory, immunosuppressive and nutritional drugs, the purpose of treating ulcerative colitis is achieved. It provides a new treatment method for invalid cases in internal surgery.
3.6 Chinese medicine treatment
(1) TCM therapy
At present, the pathogenesis of ulcerative colitis is still unclear. Although some progress has been made in the study of pathogenesis and the choice of western medicine has also increased, most of them are used to treat ulcerative colitis with many adverse reactions. At the same time, biological agents are expensive, and the efficacy of fecal bacterial transplantation has also been reported. In this case, the treatment of ulcerative colitis with traditional Chinese medicine has made some progress and clinical effect. According to the characteristics of clinical symptoms, ulcerative colitis generally belongs to the category of dysentery in traditional Chinese medicine. Traditional Chinese medicine believes that the main causes of the disease are exogenous pathogens and plague, internal injuries caused by improper diet, emotional internal injuries, spleen and stomach intestinal injuries. The main pathological factor of the disease is dampness, and its pathological nature is different from deficiency, cold and high temperature. Clinical treatment should follow the following principles: early dysentery, chronic dysentery, easy astringency, heat dysentery, cold dysentery, warm dysentery, cold and heat mixed, then warm and smooth; Insufficient and excessive mixing, and then slippery; Thirdly, under the guidance of clinical treatment principles, the ideas are divided into treatment and phased treatment. According to the classification and treatment, it can be divided into six syndrome types: stomach damp-heat, spleen-stomach qi deficiency, spleen-kidney yang deficiency, liver depression and spleen deficiency, spleen-stomach deficiency and cold, blood circulation promoting and blood stasis removing, and intestinal collaterals. There are six representative prescriptions: Shaoyao Decoction, Shenshen Baizhu Powder, Lizhong Shen Si Pill, Tongxie Yaofang and Sini Powder, Sijunzi Decoction plus Zhuche Pill, Shaofu Zhuyu Decoction. Staged treatment can be divided into remission stage and active stage. Clinically, the active stage is mainly pathogenic excess, and the treatment is mainly to eliminate pathogenic factors. Representative prescriptions include Shaoyao Decoction and Pulsatilla Decoction. The remission stage is mainly yang deficiency, and the treatment methods are mainly strengthening the body resistance, such as Shenbaizhu Powder and Shen Si Pill. Pulsatilla wengwen decoction is effective in treating ulcerative colitis and has become a research hotspot. Some scholars have found that Pulsatilla decoction can reduce the blocking degree of inflammation. At the same time, Pulsatilla decoction can up-regulate the expression of MUC2, thus protecting and repairing the mucosal barrier.
(2) traditional Chinese medicine enema therapy
The main pathological changes of UC are colonic mucosal ulcer and abscess, and the key to cure UC is to repair the ulcer. Traditional Chinese medicine believes that intestinal lesions are "carbuncle swelling and ulcers" and belong to the category of "internal swelling". According to the origin theory of various diseases. The internal pain of unc syndrome is caused by irregular diet, irregular hot and cold, gastrointestinal chills in internal thoracic diaphragm, cold in blood, stagnation of blood and gas, mutual combing of chills, stagnation, heat multiplication, and then purulent. Therefore, there are strict and effective treatments for ulcerative colon cancer, as well as enema with traditional Chinese medicine. The treatment method is to directly increase the concentration of drugs in the affected part of the intestine, relatively increase the surface area and duration of drugs contacting the intestine, give full play to the medicinal properties of traditional Chinese medicine, and avoid intestinal malabsorption at the same time. There is no obvious side effect on the curative effect of enema with traditional Chinese medicine in clinical application. This broadens the new way of TCM treatment and fully embodies the advantages and characteristics of TCM treatment.
Studies have shown that enema with traditional Chinese medicine can obviously reduce the inflammatory secretion of the focus mucosa and improve the local blood circulation. The longer the residence time, the more fully absorbed the liquid medicine and the faster the recovery. The better the prognosis of this disease. Song et al. Self-made enema is used to treat UC, and liquid enema with more than ten kinds of Chinese medicines is obviously beneficial to clearing away heat and promoting diuresis. In addition, compared with oral sulfur, retention enema has obvious therapeutic advantages. Husband adopts retention enema, combined with different related symptoms, and adopts different formulas, which is important to use. Finally, taking western medicine as the control group, he found that enema with traditional Chinese medicine had obvious effect, which confirmed that pretreatment with traditional Chinese medicine could reduce mucosal injury, improve clinical symptoms and reduce disease activity index. The clinical application of traditional Chinese medicine enema is simple and effective, and it is worth popularizing.
(3) other Chinese medicine treatment methods
There are many ways to treat diseases in Chinese medicine, among which acupuncture, moxibustion, massage, external use of Chinese medicine and pedicure of Chinese medicine are the most common. These methods can be used to heat meridians, relieve pain and improve clinical symptoms.
(4) Life and psychological care
At present, the occurrence of the disease is closely related to mental factors. At the same time, the course of the disease is long, most patients are nervous, depressed or anxious, and their ideological problems are serious, so it is very important to carry out psychological nursing for the disease. At the same time, the occurrence of diseases is closely related to diet, and informing patients of correct eating habits has also become a part of disease treatment. For example, soft and digestible foods should be provided and irritating foods or milk and dairy products should be avoided.
summary
According to the above research on the pathogenesis of ulcerative colitis, the main pathogenesis of UC is summarized as follows: 1. Under the influence of environmental factors, antigens such as intestinal flora or food participate in the activation of intestinal immune system. It will lead to the excessive and sustained development of intestinal immune response and eventually damage the intestinal mucosal barrier. 2. After the long mucosal barrier is damaged, its resistance will be greatly reduced and its immune function will be affected. 3. The intestinal mucosal barrier is seriously damaged, which makes the microbial flora disorder. Toxins will break through the barrier and reach the immune or vascular system, eventually making patients with ulcerative colon cancer sick. Comprehensive treatment, individualized treatment and combination of traditional Chinese and western medicine can all achieve good results.