The comorbidity rate of gastroesophageal reflux disease （GERD） and sleep disorders is high， and the two form a vicious circle through the “brain-gut axis”， which seriously impacts the patients’ quality of life. Traditional Chinese medicine （TCM）， guided by the core principles of “holistic concept” and “syndrome differentiation and treatment”， features multi-targeted therapeutic effects with minimal side effects， offering diverse intervention options for clinical practice. From the perspective of the “brain-gut axis”， this article reviews the relationship between the comorbidity of GERD and sleep disorders and systematically examines relevant research findings on how TCM regulates the “brain-gut axis” to intervene in this comorbid condition. The study reveals that the “brain-gut axis” may participate in the pathological progress of GERD accompanied by sleep disorders through pathways such as abnormalities in the secretion of brain-gut peptides （including gastrointestinal secretin）， as well as intestinal dysbiosis. By closely focusing on core pathogenic mechanisms such as “disharmony between the liver and stomach” and “insomnia due to stomach disharmony”， various approaches can be employed， including TCM formulas （e.g.， modified Sini powder combined with Zuojin pills）， external TCM therapies （e.g.， back-shu point digital acupressure）， and integrated traditional Chinese and Western medicine treatments （e.g.， modified Chaihu guizhi ganjiang decoction combined with proton pump inhibitors）. These methods can regulate the levels of neurotransmitters， gastrointestinal hormones， inflammatory factors， and the composition of intestinal microbiota associated with the “brain-gut axis”， thereby achieving simultaneous improvement in both GERD and sleep disorders.

OBJECTIVE To investigate the molecular mechanism of Tiaozhong huashi decoction in improving gastroesophageal reflux disease （GERD） by regulating endoplasmic reticulum autophagy in rat esophageal interstitial cells of Cajal （ICC） through p62 signaling pathway.METHODS After establishing a rat GERD model via the weak acid intragastric administration and irregular diet， the rats were randomly divided into model group， western medicine group [1.56 mg/（kg·d） of mosapride， 3.125 mg/（kg·d） of lansoprazole] and low-， medium- and high-dose Tiaozhong huashi decoction [4.713， 9.425， 18.85 g/（kg·d）] groups. A blank group was also set up， with 8 rats in each group. The rats in each group were intragastrically administered with corresponding liquid or normal saline twice a day for 14 days. During the intervention period， the general conditions of rats’ hair， spirit， diet and defecation were observed. After the last gavage， the pathological changes of esophageal tissue and the ultrastructure of ICC were observed. The relative expression and positive expression levels of p62， autophagy-related protein 8 （ATG8）， 200 kDa FAK family kinase-interacting protein （FIP200） and Unc-51 like autophagy activating kinase 1 （ULK1） in esophageal tissue were detected.RESULTS Compared with the blank group， rats in the model group exhibited listlessness； thickening of the esophageal basal layer， elongation of lamina propria papillae with inflammatory cell infiltration； markedly dilated endoplasmic reticulum appearing as round vacuolar cisternae with ribosome detachment； and a small number of accumulated autophagosomes. The relative expression and positive expression levels of p62， ATG8， FIP200， and ULK1 were significantly decreased （ P ＜0.05）. Compared with the model group， the above pathological injuries in the medium- and high-dose Tiaozhong huashi decoction groups had all improved to varying degrees； the damaged endoplasmic reticulum structure was repaired， and no autophagosome accumulation was observed. In particular， the relative expression levels and positive expression levels of p62， ATG8， FIP200， and ULK1 in esophageal tissue of rats in the medium-dose Tiaozhong huashi decoction group were significantly increased （ P ＜0.05）.CONCLUSIONS Tiaozhong huashi decoction ameliorated esophageal mucosal injury in GERD rats， and its mechanism was possibly associated with activation of the p62 signaling pathway and restoration of the endoplasmic reticulum structure， morphology， and autophagic capacity of ICC.

Diarrhea-predominant irritable bowel syndrome （IBS-D） is a common digestive system disease with high prevalence and recurrence rates for years， high treatment costs， and serious impacts on patients' quality of life and economic burden. Therefore， it is important to explore new and safe treatment methods. The pathogenesis of IBS-D is complex， in which the gut-brain axis is a key factor. The gut-brain axis， a bidirectional signaling pathway connecting the gastrointestinal tract and the central nervous system， regulates gastrointestinal motility， secretion， and immune responses， playing a key role in the occurrence and development of IBS-D. Up to now， antidiarrheal agents， probiotics， and neurotransmitter modulators are the main methods for the clinical treatment of IBS-D. Although they can partially curb the progression of this disease， the therapeutic effects remain to be improved. Studies have confirmed that traditional Chinese medicine （TCM） has significant advantages in the treatment of IBS-D since it can regulate the gut-brain axis via multiple pathways and targets to improve the gastrointestinal motility and strengthen immune defenses. However， there is a lack of systematic reviews on the regulation of the gut-brain axis by TCM in the treatment of IBS-D. Based on the review of IBS-D-related articles published in recent years， this paper systematically summarized the relationship between the gut-brain axis and IBS-D and the role of TCM in the treatment， providing new ideas for the treatment of IBS-D.

Acute pancreatitis （AP） is one of the most clinically common acute digestive disorders characterized by quick onset，rapid progression，severe condition，and high mortality. If the disease is not timely intervened in the early stage，it can develop into severe AP in the later stage，which damages the long-term quality of life and brings serious economic burden to patients and their families. However， the pathogenesis of this disease is complex and has not been fully explained. The generation and development of AP is closely related to many signaling pathways. Among them，Toll-like receptor 4（TLR4），as a transmembrane signal transduction receptor，can mediate immune response and inflammatory response，and play a key role in the occurrence and development of AP. Traditional Chinese medicine（TCM）can regulate the TLR4 signaling pathway with multiple targets，multiple effects，and multiple administration methods to inhibit inflammatory response，and effectively intervene in the progression of AP， which has gradually become a new craze for preventing and treating AP. Many studies have shown that TCM has obvious advantages in the prevention and treatment of AP. It can effectively treat AP by regulating TLR4 signaling pathway，strengthening immune resistance and defense，and inhibiting inflammatory response. Despite of the research progress，there is still a lack of comprehensive review on TCM regulation of TLR4 signaling pathway in the treatment of AP. Therefore，the literature on TCM regulation of TLR4 signaling pathway published in recent years was systematically reviewed and elaborated，aiming to provide new ideas for the treatment of AP and further drug development.

Hepatic fibrosis is a pathological process of chronic liver injury. Without timely intervention and treatment， liver fibrosis may eventually lead to liver cirrhosis and cancer. Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling pathway is closely associated with the occurrence and development of liver fibrosis. Based on this， this paper summarized and analyzed the mechanism and effects of active ingredients and compounds of traditional Chinese medicine improving liver fibrosis based on JAK/STAT signaling pathway. It is found that the active ingredients and compounds of traditional Chinese medicine that promote blood circulation and remove blood stasis （ingredients such as ethanol extract of Euonymus alatus and paclitaxel， as well as compounds such as Ershiwuwei songshi pill and Ganfukang）， clear away heat and toxic material （ingredients such as betulinic acid， total flavonoids from Persicaria perfoliata， as well as compounds such as Pianzaihuang and Kehuang capsules）， and sooth the liver and promote qi circulation （ingredients such as fraxetin and cucurbitacin B， as well as compounds such as Chaihu shugan powder and Xiaochaihu decoction） can all relieve liver fibrosis by inhibiting the activity of the JAK/STAT signaling pathway， reducing inflammatory reactions， and inhibiting the proliferation of hepatic stellate cells.

Gastroesophageal reflux disease （GERD） is a gastrointestinal motility disorder characterized by the reflux of gastric contents into the esophagus， leading to symptoms such as acid reflux and heartburn. The incidence of GERD is closely associated with psychological disorders， including anxiety and depression. The brain-gut axis， serving as a mediator of the bidirectional connection between the brain and the gastrointestinal tract， plays a crucial role in the occurrence and development of GERD with anxiety and depression. Various therapeutic approaches， including compound Chinese medicine internal therapy （such as Pingchong jiangni decoction， Tiaozhong huashi decoction， etc.）， combination therapy of internal and external Chinese medicine （such as Lianzhi xiere decoction combined with acupoint application， acupuncture at the back segment of governor vessel plus Chinese medication of soothing the liver and gallbladder， etc.）， and combination therapy of internal Chinese and western medicine （including Jianpi shugan decoction combined with rabeprazole， rabeprazole combined with Jianzhong jiangni decoction， etc.）， have been shown to regulate brain-gut peptides， intestinal flora， inflammatory factors and gastrointestinal hormones， thereby effectively alleviating GERD symptoms， anxiety and depression， and enhancing patients’ quality of life.

Sepsis is a life-threatening Organ Dysfunction disease caused by the dysregulated response of the body to infection.It is characterized by fever,chills,shortness of breath,altered consciousness,and even severe complications such as Multiple Organ Dysfunction Syndrome(MODS).The morbidity and mortality of this disease are high year after year,and there are problems such as large consumption of medical resources and poor prognosis,which seriously affect the quality of life and economic burden of patients.Therefore,it is important to explore new treatments with high efficiency,safety and low cost.The disease pathogenesis is complex,including inflammation imbalance is the main pathogenesis of sepsis.Mitogen-Activated Protein Kinases(MAPK)signaling pathway is a signaling pathway activated by environmental factors or inflammatory factors,which mediates proliferation,differentiation,inflammatory response and apoptosis,and plays a key role in the occurrence and development of sepsis.At present,antibiotics,fluid resuscitation and mechanical ventilation are the main methods for clinical treatment of sepsis.Although they can curb the progress of some diseases,some treatment effects are not good.A large amount of literature has confirmed that Chinese medicine intervention in sepsis has significant advantages,its through many channels,regulation and control of multiple targets,MAPK signaling pathways,inhibit inflammation,strengthening immune defense and effective in the treatment of sepsis,sepsis is current research hotspot.However,there is still a lack of systematic reviews on the regulation of MAPK signaling pathway by traditional Chinese medicine in the treatment of sepsis.Therefore,based on the retrieval database sepsis related literature at home and abroad in recent years,a systemic summary of MAPK signal pathway and sepsis relations and the role of traditional Chinese medicine in them,will be new drugs for the treatment of sepsis and development provides new theoretical support.

Sepsis is a life-threatening Organ Dysfunction disease caused by the dysregulated response of the body to infection.It is characterized by fever,chills,shortness of breath,altered consciousness,and even severe complications such as Multiple Organ Dysfunction Syndrome(MODS).The morbidity and mortality of this disease are high year after year,and there are problems such as large consumption of medical resources and poor prognosis,which seriously affect the quality of life and economic burden of patients.Therefore,it is important to explore new treatments with high efficiency,safety and low cost.The disease pathogenesis is complex,including inflammation imbalance is the main pathogenesis of sepsis.Mitogen-Activated Protein Kinases(MAPK)signaling pathway is a signaling pathway activated by environmental factors or inflammatory factors,which mediates proliferation,differentiation,inflammatory response and apoptosis,and plays a key role in the occurrence and development of sepsis.At present,antibiotics,fluid resuscitation and mechanical ventilation are the main methods for clinical treatment of sepsis.Although they can curb the progress of some diseases,some treatment effects are not good.A large amount of literature has confirmed that Chinese medicine intervention in sepsis has significant advantages,its through many channels,regulation and control of multiple targets,MAPK signaling pathways,inhibit inflammation,strengthening immune defense and effective in the treatment of sepsis,sepsis is current research hotspot.However,there is still a lack of systematic reviews on the regulation of MAPK signaling pathway by traditional Chinese medicine in the treatment of sepsis.Therefore,based on the retrieval database sepsis related literature at home and abroad in recent years,a systemic summary of MAPK signal pathway and sepsis relations and the role of traditional Chinese medicine in them,will be new drugs for the treatment of sepsis and development provides new theoretical support.

Ulcerative colitis （UC） is a chronic non-specific inflammatory disease characterized by the damage of the epithelial barrier of the colon and the destruction of immune homeostasis. It has a long course， no recovery and high recurrence rate， and is recognized as a difficult digestive disease. MicroRNA （miRNA） has been confirmed to be specifically or differentially expressed in both UC patients and UC animal models， so miRNA can be used as markers for UC diagnosis or reference for treatment evaluation. TCM therapy has a definite therapeutic effect， a wide range of effects， and minimal side effects in the treatment of UC， so this article takes miRNA as the starting point and systematically elaborates on the mechanism of TCM regulating UC related signaling pathways by regulating the expression of miRNA. The results show that chlorogenic acid， Anchang decoction， and Fuyang huoxue jiedu formula can regulate the expressions of miR-155， miR-146a and miR-31-5p， etc.， thereby inhibiting signal transducer and activator of transcription （STAT） signal pathway transduction to improve UC. Limonin， ginsenoside Rh2， artesunate， etc. can inhibit nuclear factor-κB （NF-κB） signaling pathway conduction to improve UC by regulating the expressions of miR-214， miR- 155 and miR-19a， etc. Nitidine chloride， berberine， resveratrol， etc. can regulate the expressions of miR-31， miR-146a， miR- 146b， etc.， thereby inhibiting the Toll-like receptor 4 （TLR4） signaling pathway to improve UC. Mango polyphenolics， Compound qinbai granules， and Astragalus membranaceus polysaccharides can regulate the expressions of miR-126 and miR-193a-3p， thereby inhibiting the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/AKT/mTOR） signaling pathway to improve UC.

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.