preface
Ulcerative colitis (UC) is a chronic, non-specific intestinal inflammatory disease whose pathogenesis is unknown. In recent years, the incidence and incidence of the disease have increased year by year, and it has become a new treatment.
With the increasing number of severe and refractory diseases and the continuous development of diseases, it is no longer possible to rely on Western medicine or traditional Chinese medicine alone to meet clinical needs.
The combination of traditional Chinese medicine and Western medicine has greater advantages in improving the patient's condition, improving the patient's quality of life and saving medical resources. On this basis, how to better play the advantages of Chinese medicine and Western medicine, as well as the combination of Chinese medicine and Western medicine and the choice of timing, need to be discussed in depth.
Challenges in UC treatment
In recent years, the incidence and incidence of UC has been increasing rapidly worldwide. Western Europe and North America are the countries with the largest incidence of UC, with Norway and the United States with 5.05 million and 2.86 million respectively.
In newly industrialized countries such as Asia and South America, the incidence and incidence of UC are also increasing year by year. The prevalence of UC in Korea increased from 0.34 per 100 000 in 1986-1990 to 3.08 per 100 000 in 2001-2005.
Since 1990, the incidence of ulcerative colitis (UC) in Brazil has increased by 75% and is increasing at an annual rate of 14.9%. At present, there are no systematic and comprehensive reports on the disease in China.
According to statistics, in Taiwan, the incidence of the disease is 105/4.59; in Hong Kong, it is 3.06 per 105 people; 3.44 cities in 105 cities in Guangzhou; and 0.42 in 105 cities in Xi'an. The reports from these regions do not yet fully reflect the rapidly growing number of patients in the country.
At present, 5-aminosalicylic acid (5-ASA), glucocorticoids, immunomodulators, biological agents, and traditional Chinese medicine are mainly used in clinical practice, but its mechanism of action is not clear. 5-ASA is recognized as an essential drug for UC due to its strong antimicrobial activity and strong antimicrobial activity.
The evidence-based consensus published by ECCO and my 2018 Consensus on the Diagnosis and Treatment of Inflammatory Bowel Disease both refer to 5-ASA as the drug of choice for mild and moderate UC, and maintenance therapy during remission.
A UCM eta analysis of mild, moderate, and remission showed that UC was 50.5% topical and 41.3% oral. The ADR for topical drugs was 22/105 (21.0%) and for oral drugs was 36/109 (33.0%).
Glucocorticoids significantly reduce mortality in patients with severe UC. Corticosteroids are not used as maintenance therapy because they cause hormone-dependent and hormonal resistance, as well as side effects such as adrenal insufficiency and osteoporosis.
Our group conducted clinical trials on budesonide foam in the early stage, and the results showed that the incidence of adverse reactions was 45.9%. Immunosuppressants are used to treat refractory UC, mainly for the treatment of hormone-dependent diseases.
One meta-analysis showed that AZA/6-MP was between 42% and 79% effective, but prone to side effects such as nausea, vomiting, abdominal pain, severe diarrhea, bone marrow suppression, hepatotoxicity, and pancreatitis.
In recent years, the emergence of a variety of biological agents has provided new ideas for the prevention and treatment of UC. After meta-analysis of patients with moderate to severe UC, infliximab evoked a response of 34-39% and maintained a response of 50%; adalimumab was 10-21% and 2-23-37%, respectively; The positive rates of vedolizumab were 23% and 37%-46%, respectively.
The East Asian study showed that the total effective rate and mucosal healing rate of patients with 10 mg/day twice a day were 66.7% and 57.1%, respectively, in 52 weeks of tofacitinib treatment, which was significantly higher than that of the placebo group.
However, its high cost is high, mostly used in severe or refractory patients, can not effectively improve the clinical efficacy of patients, and is prone to lymphoma/tumor, blood diseases, liver toxicity and other complications, resulting in reduced drug efficacy. The above two drugs have a good effect on improving the clinical symptoms of UC patients, but they cannot meet the clinical needs.
Efficacy and mechanism of traditional Chinese medicine in the treatment of UC
The therapeutic effect and mechanism of UC are related to the functional disorders of the spleen, liver, kidney, lung and other organs in the large intestine. This virtual standard is the main pathogenesis of UC, and the main pathogenesis is humidity, heat and stasis.
The period of blood circulation and stasis is mostly standardized, and the pathogenesis is mainly humid heat, accompanied by stasis and heat loss; Severe cases are mainly characterized by heat toxicity and stasis, and if it cannot be healed repeatedly, sputum turbidity and blood stasis need to be considered.
In the recovery period, the deficiency is mainly accompanied by humid fever, while the deficiency is mainly spleen deficiency, supplemented by kidney deficiency. Traditional Chinese medicine has a definite therapeutic effect on ulcerative colitis.
In our previous work, we found that after 8 weeks of andrographolide administration, Qingdai cleared heat and detoxification, cooled blood and eliminated spots, and had the effect of "treating puerperal fever and diarrhea" in the "Benjing Fengyuan".
A multicenter, clinical study of Cindai in the treatment of UC showed that the clinical response rate, remission rate and mucosal healing rate of the treatment group were significantly higher than those in the placebo group (P<0.05). Our research group carried out a multi-center randomized controlled study in the early stage and found that traditional Chinese medicine has a significant efficacy in the treatment of UC.
The experimental group was administered sequentially, and the postoperative recurrence rate was 13.24% versus 14.58%.The treatment group controlled pus and blood stool faster than the control group, and the rate of abdominal pain disappearance after 16 weeks was higher than that of the control group.
Previous research on the mechanism of action of UC has shown that colon cleansing and wet formula exerts anti-inflammatory, immunomodulatory and intestinal mucosal repair effects by regulating NF-κ B signaling pathway.
For example, it can inhibit NF-κ B nucleation, reduce the expression of CD40 and MHCII on the DC surface, affect the maturation and differentiation of DC, and reduce its antigen presentation function. It can also inhibit the activation of the JAK/STAT3 signaling pathway, prevent the phosphorylation activation of STAT3 from entering the nucleus, and then alleviate the inflammatory response.
In addition, it can also reduce the expression of pro-inflammatory factors TNF-α, IL-1β, IL-23 and IL-17 in the colonic tissues of UC rats, and promote the release of TGF-β. Previous research in our group found that strengthening the spleen and tonifying the kidney, cleansing the intestines and wetting Chinese medicine can promote the homing of MSCs in the UC injured intestine, and can induce the directional differentiation of MSCs to intestinal stem cells and repair intestinal damage.
The previous research of our group found that the cleansing and wet prescription drugs had a significant improvement effect on the expression of occludin and ZO-1 in the intestinal tissues of UC rats, and its mechanism of action was related to its effect on the adhesion molecule Muc.2 of UC rat intestinal epithelial cells. Curcumin has anti-inflammatory, antioxidant and intestinal mucosal repair functions in UC, but the specific mechanism is unknown.
We used Yunnan baiyao gavage UC mice, using isotonic normal saline as the control group, and found that after Yunnan baiyao gavage, colon inflammation was reduced, and the expression of inflammatory factors such as TNF-α, IL-12p40, IL-17, INF-γ and other inflammatory factors was significantly reduced.
Advantages and clinical application of integrative medicine in the treatment of UC
In summary, both traditional Chinese medicine and Western medicine have a bottleneck in the efficacy of UC, especially for refractory UC, and it is urgent to develop more effective treatment methods. The combination of traditional Chinese and Western medicine has its unique advantages in the treatment of UC.
From induction of remission to maintenance of remission, reduce complications, gradually move to rapid remission, reduce long-term use of hormones, thoroughly repair mucosa, maintain remission for a long time, prevent complications, reduce the rate of postoperative hospitalization, reduce the risk of cancer, and improve the quality of life of patients.
In recent years, new ideas of "deep remission" (including clinical remission, endoscopic remission, tissue remission) and "meeting the standard" have been proposed.
With the improvement of efficacy and efficacy, existing treatment methods are also facing greater challenges. Biologics are effective in promoting and maintaining mucosal healing.
Meta-results showed that the treatment effect of this combination in moderate to severe ulcerative colitis could reach 29% to 60%; The mucosal healing rate in UC patients with severe ulcerative colitis (UC) is 52% to 65%.Even with biologic agents, a significant number of patients are unable to undergo mucosal repair.
However, healing of the mucous membrane does not mean the disappearance of symptoms. Some patients are immobile by gastroscopy, but the clinical manifestations remain severe. On the basis of Western medicine, the dialectical treatment method of traditional Chinese medicine can effectively improve the patient's condition, enable the patient to obtain a better recovery effect, and thus improve the patient's quality of life.
Achieving standard treatment requires strict treatment goals that not only promote clinical remission, but also focus on mucosal healing and histologic remission.
At the same time, it also focuses on personalized treatment, through the evaluation of efficacy, continuous adjustment of treatment plan, and then continuous improvement of efficacy, which is very consistent with the methods and strategies of TCM dialectical treatment.
The combination of "standard-attaining" therapy and TCM dialectical treatment, giving full play to the advantages of multi-component and multi-target of TCM compounds, and carrying out dialectical treatment according to the changes of the disease, is more conducive to achieving deep remission.
In addition, integrated Chinese and Western medicine also has great advantages in health economy, and its benefits, potency and efficiency will be improved, which can reduce the dependence on biological products and other drugs, and save medical resources.
For people suitable for western drug treatment, the UC lesion degree, lesion location, disease stage, and parenteral manifestations should be used as the criteria to determine the suitable population for western drug treatment. Patients with mild or moderate active UC can choose a combination of traditional Chinese and Western medicine for treatment.
If symptoms do not improve well, either fecal occult blood is positive, or the colonic mucosa has not reached the point of healing. For severe or refractory UC, a combination of Western medicine should be used at the same time.
Patients with rectum, sigmoid colon and left colon can choose a simple combination of Chinese and Western medicine. For patients with extensive colitis or extraintestinal symptoms, Western medicine must be used at the same time.
For UC with special conditions such as pregnancy, anemia, malnutrition, etc., or UC with irritable bowel syndrome with abdominal pain and diarrhea, diarrhea and other symptoms, a combination of traditional Chinese and Western medicine can also be performed. During the period of remission, Chinese medicine can be taken as well as Western medicine.
The idea and method of combining traditional Chinese medicine and Western medicine to treat UC, TCM treatment UC has its own characteristics and its own defects. Therefore, how to combine Chinese and Western medicines to treat UC, we should adopt appropriate methods and strategies according to the specific conditions of UC patients, so as to maximize the advantages of combination therapy of Chinese and Western medicines and realize the classification, grading, staging and differentiation of UC patients.
With colon cleansing and dampness as the mainstay, anti-inflammatory, and colon cleansing and moisture, TCM believes that "moist heat and depression" is an important pathogenesis of active UC.
The combination of Western medicine and colon cleansing and wet method can effectively relieve inflammation in the small intestine and promote disease progression. Coptis acorifa, scutellaria baicalensis, yellow cypress, bitter ginseng (woody fragrance), Qin peel, purslane and ground brocade are all common Chinese medicines in clinical practice.
Yu Yuan et al. divided 60 UC patients into two groups, one group with mesalamine enteric-coated tablets, the other group with medication, and the other group with medication, namely Peony Huang An Guo Soup.
After the completion of the course of treatment, the main clinical symptoms (abdominal pain, diarrhea, tenesmus, pus and bloody stool), endoscopic scores, and CD8+ levels of the two groups were significantly improved, and the observation group was more significant than the control group.
The combination of cool blood stasis and anti-inflammatory can quickly reduce clinical symptoms, while humid heat causes stasis, and heat stasis damage is its basic pathogenesis, emphasizing that cool blood stasis can help improve the treatment effect of pus and bloody stool.
Chinese medicines such as Diyu, comfrey, and madder are all common Chinese medicines in clinical practice. A multi-center randomized controlled study in our group found that the treatment of pus and blood symptoms by colon cleansing and wet prescription combined with Chinese proprietary medicine enema was faster and more efficient than mesalazine.
Deng Wenjun et al. studied the treatment of UC with mesalazine combined with danshen injection, the control group took mesalazine, and the observation group took danshen injection in combination with the control group on this basis. There were significant differences between the observation group and the control group.
The total effective rate of clinical treatment of pus and bloody stool was higher than that of the control group (94.5% vs. 80.0%, P<0.05), and the contents of inflammatory factors TNF-α, IL-6 and IL-8 decreased significantly (P<0.05).
Anti-inflammatory matching, to "collect ulcers and muscles" to promote mucosal healing, Western medicine to anti-inflammatory, with traditional Chinese medicine on the protection of the intestinal mucosa, to achieve the purpose of "ulceration and muscle", clinically commonly used traditional Chinese medicines are: white ji, ginseng three seven, blood exhaustion, catechin, raw astragalus, white peony, calamine, plum, diyu, jizi, red stone resin, pomegranate peel, quintuple seed, white alum, yellow cypress, Qingdai and so on.
According to the characteristics of the drug, it can be divided into two ways, one is oral, the other is enema, especially traditional Chinese medicine enema, can play a dual role of chemical and physical effects, can quickly relieve the clinical symptoms of patients, but also can accelerate the healing of mucosal ulcers.
Compared with the method of enteric-coated tablets plus berberine and Yunnan baiyao gavage using mesalazine enteric-coated tablets plus berberine and Yunnan baiyao (P<0.05), the results showed that it had an improving effect on the intestinal mucosa.
Anti-inflammatory, spleen and qi are the main ones, spleen and qi, kidney and yang, kidney and qi are the basic pathogenesis and pathogenesis of UC, and it is the main treatment for consolidating efficacy and preventing recurrence. UC has a long course of disease, mostly showing a combination of "positive" and "evil", with "strengthening the spleen and strengthening qi, supporting the right and consolidating the root" as its treatment.
Therefore, TCM takes the method of strengthening the spleen and invigorating qi as the main treatment method, supplemented by Western medicine anti-inflammatory, which is not only conducive to maintaining remission and preventing the recurrence of the disease, but also restoring intestinal function, improving nutritional status, and achieving the purpose of rejuvenation and dampness.
Commonly used Chinese medicines include astragalus, baiju, poria, yam, codonopsis, chia and so on. Zou Hao et al. used the randomization method to divide UC patients with spleen and stomach deficiency into two groups, one for treatment and the other for control. The two groups of patients took two drugs, one was to strengthen the spleen and the other was mesalazine.
Results: After 8 weeks of treatment, the clinical symptoms of mucopurulent stool, diarrhea and abdominal pain in both groups improved significantly. The treatment response rate, disease activity index, inflammatory index ESR, C-reactive protein level, and remission time of the main clinical symptoms of the two groups were significantly better than the control group.
The results show that the combined application of anti-inflammatory, spleen and qi invigoration methods in Western medicine can not only reduce inflammation and improve the physical fitness of patients, but also make patients' conditions significantly improved.
The main ways of using integrated traditional Chinese and Western medicine are: combination of traditional Chinese and Western medicine oral, western medicine enema, western medicine local treatment, western medicine combined enema, traditional Chinese medicine combined enema, etc. Serotonin (5-ASA) is currently the most widely used western drug combination mode.
Conclusion: On the basis of traditional Chinese medicine, the application of glucocorticoids can enhance the effect of drugs and reduce the tolerance, dependence and toxic side effects of drugs. The combination of traditional Chinese medicine and immunomodulatory drugs can achieve the purpose of attenuating, increasing efficiency and improving efficacy.
perspective
At present, there are three treatment methods for UC: Western medicine, Chinese medicine, and Chinese and Western medicine; Commonly used drugs are intravenous, oral, topical (suppositories, sparing enemas), oral and topical.
The advantage of TCM is that it emphasizes the holistic view, dialectical treatment, to regulate the function of the internal organs, to eliminate the disease, so as to achieve the purpose of curing diseases. The mechanism of Western medicine treatment is clear and well documented.
By combining the two, complementary advantages can be achieved and efficacy can be improved. At its core is the lack of high-quality, evidence-based clinical evidence. Based on the previous work, this project intends to take UC patients as the research object, "integrated traditional Chinese and Western medicine" as the entry point, UC patients as the research object, and "integrated traditional Chinese and Western medicine" as the entry point.
Carry out research on the mechanism of "integrated traditional Chinese and Western medicine" in the intervention of intestinal immune function in UC patients, and the intervention of "integrated traditional Chinese and western medicine" in UC-related colorectal cancer. We believe that on the basis of multicenter, large sample, randomized, double-blind, and multidisciplinary intersection, it will contribute to the in-depth study of the pathogenesis of UC.
Resources
[1] Shen Hong, Zhang Shengsheng, Wang Chujie, et al. Clinical observation of 111 cases of mild and moderate ulcerative colitis. Chinese Journal of Traditional Chinese Medicine, 2011.
[2] ZHAO Qingchun, SHEN Hong, CHENG Haibo, et al. Regulatory effect of colon cleansing formula on IL-6/JAK2/STAT3 signaling pathway in tumor cells. Chinese Journal of Materia Medica, 2015.
[3] Shen H, Liu Zhiqun, Zhu Quan, et al. Intervention effect and possible mechanism of colon cleansing and wet formula on NF-kB/Tolls signaling pathway[J].Chinese Journal of Chinese and Western Materia Medica, 2013.
[4] LU Yuelin, SHEN Hong, YAO Hongfeng, et al. Effects of colon cleansing and mesalazine on IL-17 expression in serum and intestinal mucosa in rats with ulcerative colitis. Chinese Journal of Traditional and Western Materia Medica, 2014.
[5] ZHU Lei, SHEN Hong, GU Peiqing, et al. Effects of kidney and qi invigoration, colon cleansing and moisture-clearing formula and bone marrow mesenchymal stem cells on intestinal mucosal barrier function in rats with ulcerative colitis. Chinese Journal of Gastroenterology, 2016.