Ulcerative colitis （UC） is a chronic inflammatory bowel disease with complex etiology. The pathogenesis of this disease， due to a combination of factors， is complex and has not yet been elucidated. Among them， intestinal mucosal barrier damage is the basic pathological change of UC. As a non-destructive response of cells， autophagy regulates intestinal mucosal immunity， inflammation， oxidative stress， and bacterial homeostasis through degradation and reabsorption to actively repair damaged intestinal mucosal barrier， exerting a key role in the occurrence and development of UC. The disease is mainly treated clinically with aminosalicylic acid preparations， glucocorticoids， and immunosuppressants. Western medicine treatment of the disease has a fast onset of effect， and the short-term efficacy is definite， but the long-term application is easy to be accompanied by more adverse reactions. Moreover， some drugs are expensive， bringing great physical and mental pain and economic burden to patients. Therefore， it is urgent to explore new therapies with stable efficacy and mild adverse effects. In recent years， a large number of studies have shown that Chinese medicine can regulate autophagy of the intestinal mucosa with multiple targets and effects and repair the intestinal mucosal barrier function， thereby inhibiting the development of UC. Many experiments have shown that the active ingredient or monomers and compound formulas of Chinese medicine can improve the immunity of the intestinal mucosa， inflammation， oxidative stress， and flora by regulating the level of autophagy to maintain the normal function of the intestinal mucosal barrier to effectively intervene in UC， providing a new measure for the prevention and treatment of UC. However， there is a lack of systematic review of Chinese medicine in regulating the level of autophagy in the intestinal mucosa for the prevention and treatment of UC. Therefore， based on the current research on UC， autophagy process， and Chinese medicine treatment， this article reviewed the relationship of autophagy and its key target proteins with UC to clarify the key role of autophagy in UC production and systematically summarized Chinese medicines targeting the regulation of autophagy to treat UC in recent years to provide new ideas for the treatment and drug development of UC.

Ulcerative colitis （UC） is a chronic， non-specific inflammatory bowel disease. The pathogenesis of this disease is complex and is attributed to multiple factors. Intestinal mucosal barrier damage is the basic pathological change of UC， and intestinal flora disorder is one of the important characteristics of UC. Intestinal flora plays a key role in the pathological process of UC by regulating intestinal mucosal immunity and inflammatory response to repair the damaged intestinal mucosal barrier. At present， western medicine has the advantages of rapid action onset and significant short-term efficacy， but the curative effect of long-term use is not good， accompanied by many adverse reactions， causing great physical and mental pain to patients. Therefore， it is urgent to explore new treatment methods with definite long-term efficacy and mild adverse reactions. A large number of studies have shown that Chinese medicine can regulate intestinal flora through multiple targets in an all-around way， restore the homeostasis of the flora， and repair the damaged intestinal mucosal barrier， thereby inhibiting the progression of UC. Numerous studies have shown that the active components， monomers， and compounds of Chinese medicine can effectively antagonize UC by regulating the intestinal flora to improve the intestinal mucosal immunity， reduce the inflammatory response of the intestinal mucosa， and restore the normal physiological function of the intestinal mucosal barrier， providing a new strategy for UC prevention and treatment. Although there are some studies of the regulation of intestinal flora by Chinese medicine to prevent and treat UC， those studies have the shortcomings of systematic and comprehensive inadequacy. Therefore， based on the research status of UC， intestinal flora， and Chinese medicine treatment， this study reviewed the relationship between intestinal flora and UC and clarified the key role of intestinal flora in the occurrence and development of UC. At the same time， this paper comprehensively summarized the Chinese medicine that targeted the regulation of intestinal flora for the treatment of UC in the past five years to provide new strategies and ideas for UC treatment.

Background::Heterotaxy (HTX) is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease (CHD). The aim of this study was to analyze rare copy number variations (CNVs) in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/CHD.Methods::Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients, and available samples from parents were used to confirm the inheritance pattern. Potential candidate genes in CNVs region were prioritized via the DECIPHER database, and PNPLA4 was identified as the leading candidate gene. To validate, we generated PNPLA4-overexpressing human induced pluripotent stem cell lines as well as pnpla4-overexpressing zebrafish model, followed by a series of transcriptomic, biochemical and cellular analyses. Results::Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients (12.5%). Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort, and PNPLA4 in the Xp22.31 was a candidate gene associated with HTX/CHD. PNPLA4 is expressed in the lateral plate mesoderm, which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation, and in the neural crest cell lineage. Through a series of in vivo and in vitro analyses at the molecular and cellular levels, we revealed that the biological function of PNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP production. Conclusions::Our findings demonstrated a significant association between CNVs and HTX/CHD. Our data strongly suggested that an increased genetic dose of PNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.

Ulcerative colitis （UC） mainly occurs in the colon and rectum， with complex pathological mechanism. The occurrence of ulcerative colitis is associated with the uncontrollable inflammatory response of the intestine. The Western medicine therapy of UC mainly uses glucocorticoids and immunosuppressants to reduce intestinal inflammation. While blocking the progress of UC to a certain extent， it causes severe adverse reactions. More and more studies have confirmed that traditional Chinese medicine （TCM） has obvious advantages in the prevention and treatment of UC and can significantly reduce the recurrence of the disease. Pyroptosis， a novel form of cell death， can destroy cell structure， release intracellular pro-inflammatory substances， and mediate intestinal immune response in UC. TCM can promote pyroptosis （removing excess） or inhibit pyroptosis （replenishing deficiency）， which is consistent with the regulation of Yin and Yang. TCM plays a role in the treatment of UC mainly by inhibiting pyroptosis （replenishing deficiency） and reducing intestinal immune response. In recent years， a large number of studies have been carried out to decipher the mechanism of TCM in the treatment of UC via NOD-like receptor protein domain 3 （NLRP3）-mediated pyroptosis pathway. The results have demonstrated that NLRP3 pathway is the key target of TCM in the treatment of UC. However， a comprehensive summary remains to be carried out on the inhibition of NLRP3-mediated pyroptosis pathway by TCM in the treatment of UC. Therefore， we retrieved the articles in this field in recent years with the keywords "pyroptosis"， "NLRP3"， "ulcerative colitis"， and "Chinese medicine". The Chinese medicines regulating NLRP3 pathway mainly have the functions of clearing heat and drying dampness， harmonizing Qi and blood， moving Qi and dredging fu-organs， and invigorating spleen and removing dampness. The findings can help researchers to fully understand the mechanism of TCM in the treatment of UC via the NLRP3 pathway and provide a theoretical basis for the treatment of UC and further drug development.

Ulcerative colitis （UC）， a disease that affects the colon or rectum， is characterized by long-term recurrent inflammation and eventually leads to ulcers in the inner wall of the intestine. The disease has a high incidence and is difficult to be cured， which causes severe physical and mental discomfort and economic burden to the patients. Therefore， it is urgent to develop new therapies with high cure rate and low side effect. The pathological mechanism of UC is complex and involves multiple factors. The intestinal mucosal barrier damage is the main pathological basis of UC， which is a hot topic and a new research direction. Intestinal tight junction （TJ）， as the structural basis of the intestinal mucosal mechanical barrier， can actively regulate mucosal function and play a key role in the pathogenesis of UC. Traditional Chinese medicine （TCM） can regulate TJ protein via multiple pathways and multiple targets， repair the intestinal mucosal barrier， and thus block the progression of UC. Studies have demonstrated that Chinese herbal medicines and their components， Chinese medicine compound prescriptions， and Chinese medicine preparations can treat UC by regulating TJ protein to maintain the function and reduce the permeability of intestinal epithelium， providing a new therapeutic strategy for UC. Although TCM has unique advantages that western medicine cannot replace by mediating TJ protein expression in UC， a comprehensive review of this field remains to be carried out. Focusing on the status of UC and TCM syndrome differentiation and treatment， we retrieved relevant articles with ''ulcerative colitis''， ''tight junction''， and ''Chinese medicine'' as the keywords， and summarized the relationship of TJ and its key target proteins with UC to clarify the critical role of TJ in UC pathophysiology. Furthermore， we summarized the Chinese medicines regulating TJ in the treatment of UC in recent years， aiming to provide a theoretical basis for the development of drugs for this disease.

Ulcerative colitis （UC） is a disease that affects the mucosal and submucosal layers of the colon and is characterized by inflammation of the intestinal mucosa. The incidence of UC is increasing year by year， and it is complex and refractory， severely impacting the physical and mental health of patients. The pathological mechanism of this disease is complex， with immune responses and uncontrollable inflammatory reactions in the intestine being important physiopathologic mechanisms. Toll-like receptor 4 （TLR4）， as a transmembrane signaling receptor， plays a key role in mediating immune responses and inflammatory reactions in the development of UC. Currently， the treatment of UC mainly relies on salicylic acids， glucocorticoids， and other agents to reduce intestinal inflammation. While these drugs can partially inhibit the progression of the disease， they often come with significant adverse effects and the potential for relapse upon discontinuation. Traditional Chinese medicine （TCM） offers multiple pathways， effects， and targets for regulating the TLR4 pathway， suppressing inflammatory responses， and effectively intervening in the progression of UC. This approach has become a hot topic in the prevention and treatment of UC. Numerous studies have shown that TCM treatment of UC has unique advantages. TCM can enhance immune defenses， suppress inflammatory responses， promote intestinal mucosal healing， and maintain the balance of the intestinal microbiota by regulating the TLR4 signaling pathway， thereby effectively treating UC， with substantial progress achieved. However， there is currently a lack of comprehensive reviews on the role of TCM in regulating the TLR4 signaling pathway for the treatment of UC. Therefore， this article systematically summarized the relationship between the TLR4 signaling pathway and UC， as well as the role of TCM in this context， by reviewing relevant literature from recent years， aiming to provide new insights into the potential treatment and new drug development for UC.

Ulcerative colitis （UC） is a clinical chronic intestinal disease， and the damage of the intestinal epithelial mucus barrier is an important pathological mechanism of UC. Mucin 2 （MUC2） is a major component of the intestinal mucus barrier， and goblet cells are the “main force” of MUC2 secretion， maintaining and renewing the intestinal mucus layer to ensure its integrity. Therefore， repairing the intestinal mucus barrier by promoting the synthesis of MUC2 by goblet cells is an important strategy for the treatment of UC. Traditional Chinese medicine scholars believe that there is an inherent layer of “lipid membrane” or “fat paste” in the intestine， and pathological factors such as moisture and heat lead to the thinning of this structure， which is the fundamental pathogenesis of “diarrhea” and “intestinal dysentery”. It coincides with the damage of intestinal mucus barrier leading to UC in modern medicine. Based on this， this paper summarized the mechanism of Chinese herbal compounds or Chinese herbal active components in regulating intestinal mucus barrier to interfere with UC. It was found that Chinese herbal compounds such as Huanglian jiedu decoction， Shaoyao decoction and Compound Kusen decoction， as well as Chinese herbal active ingredients such as volatile oil of Atractylodes lancea， paeoniflorin and papaya triterpenes could promote the synthesis and secretion function of goblet cells， and achieve the purpose of “thickening intestine”， thus relieving UC symptoms.

Gastric cancer （GC） is a digestive tract tumor that occurs in the epithelial tissues of the gastric mucosa， seriously affecting the life and health of patients， and its mortality rate ranks the third among malignancies. Although medical technology has made great progress in recent years， the progression of GC still cannot be effectively controlled by surgery， chemotherapy， and targeted therapy. The pathogenesis of GC is extremely complex and is closely related to the tumor microenvironment， chronic inflammation， and immune escape， among which the reduction of tumor cell apoptosis is one of the important mechanisms for the occurrence and development of GC. Apoptosis refers to the process of spontaneous termination of cell life caused by genes under specific physiological or pathological conditions， which is of great significance for maintaining the stability of the internal environment. Researchers have found that in the GC state， mitochondrial endogenous apoptosis， endoplasmic reticulum stress， external death receptors， and other apoptosis pathways are regulated by multiple signaling pathways and genes， which together lead to the decline of GC cell apoptosis rate and thus promote the progression of GC. Chinese medicine is advantageous and characterized by multiple components， multiple targets， synergistic effect， and few adverse reactions. A large number of studies have shown that polysaccharide components， as effective components of Chinese medicine， have biological activities such as cancer inhibition， blood sugar control， anti-inflammation， antioxidant damage， and anti-virus， and can effectively inhibit the deterioration of GC by inducing cell apoptosis， gradually becoming a hot spot in GC drug research and development. However， systematic reviews on the apoptosis of GC induced by Chinese medicine polysaccharides are rarely reported. Therefore， this paper analyzed and summarized the studies of Chinese medicine polysaccharides in promoting apoptosis and interfering with GC， in order to provide a theoretical basis for the basic research， new drug development， and clinical application of Chinese medicine polysaccharides in the intervention of GC.

Diarrhea-predominant irritable bowel syndrome （IBS-D） is a chronic intestinal disease characterized by abdominal pain and increased water content in stool. The pathological mechanism of this disease is complex and attributed to many factors， where the impairment of intestinal mucosal barrier is pivotal in the pathogenesis of IBS-D. The intercellular tight junction （TJ）in intestinal mucosa is mainly composed of Occludin，Claudins， and zonula occludens （ZOs），which is an important component of mechanical barrier and can significantly affect mucosal function. Since modern medicine holds that the pathogenesis of this disease is not fully revealed，symptomatic treatment is the first choice in clinical practice even though the outcomes are not satisfactory. According to traditional Chinese medicine （TCM），the epithelial barrier function in intestinal mucosa corresponds to the TCM theory of "the spleen acts as the guard". Many studies have reported that the active components of Chinese medicine and compound prescriptions can restore the intestinal epithelial barrier function of IBS-D rats by regulating TJ protein，reduce its permeability， and inhibit intestinal water and electrolyte exudation，thereby improving symptoms. This study reviewed the relationship of IBS-D with TJ and its key target proteins to clarify the key role of TJ in the pathophysiology of IBS-D and summarized the TCM treatment of IBS-D through the target regulation of TJ， with the purpose to provide a theoretical basis for the treatment of IBS-D and further drug development.

Ulcerative colitis（UC）is a disease characterized by chronic persistent inflammation of the colorectal mucosa. Its complex pathological mechanism is related to immune inflammation and enhanced apoptotic activity. The Janus kinase（JAK）/signal transducer and activator of transcription（STAT）is an important regulatory pathway in the body's physiological function, which can regulate the release of intestinal pro-inflammatory factors and induce apoptosis, resulting in colon tissue damage. In the condition of UC, the biological activities and expression levels of JAK and STAT increased, and the tissue inflammatory response and apoptosis rate increased, which led to the destruction of intestinal mucosal tissues. At present, in the treatment of UC, glucocorticoids and immunosuppressants are mainly employed to reduce intestinal inflammation. Although they can block the progress of UC to some extent, the adverse reactions are severe. A large number of studies have shown that traditional Chinese medicine（TCM） has significant advantages in the prevention and treatment of UC and can significantly reduce the recurrence rate of this disease. In recent years, plenty of studies have been carried out to explore the role of TCM in the treatment of UC by regulating the JAK/STAT pathway. The results have shown that the JAK/STAT pathway is the key target pathway of TCM in the treatment of UC. Based on the etiology and pathogenesis of deficiency and excess, TCM regulates the JAK/STAT pathway by clearing heat, drying dampness, cooling and activating blood, invigorating the spleen, warming the kidney, and performing both tonification and elimination to maintain the balance between pro-inflammatory factors and anti-inflammatory factors, weaken colonic inflammatory response, inhibit apoptosis, and play a role in the treatment of UC. The present study analyzed the mechanism and effect of TCM in intervening in UC by targeting the JAK/STAT signaling pathway and summarized the molecular mechanisms of different cytokines such as interleukin-6（IL-6）, IL-10, IL-23, microRNA（miRNA）-146a, and suppressors of cytokine signaling 2/3（SOCS2/3） on many family subtypes of the JAK/STAT signaling pathway to facilitate the comprehensive understanding of researchers on the mechanism of TCM on the JAK/STAT pathway in UC, which is expected to provide a theoretical basis for the treatment of UC and further drug development.