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.

PURPOSE: To assess the relationship between dislocation and functional outcomes in supination-external rotation (SER) ankle fractures. METHODS: A retrospective case series study was performed on patients with ankle fractures treated surgically at a large trauma center from January 2015 to December 2021. The inclusion criteria were young and middle-aged patients of 18 - 65 years with SER ankle fractures that can be classified by Lauge-Hansen classification and underwent surgery at our trauma center. Exclusion criteria were serious life-threatening diseases, open fractures, fractures delayed for more than 3 weeks, fracture sites ≥ 2, etc. Then patients were divided into dislocation and no-dislocation groups. Patient demographics, injury characteristics, surgery-related outcomes, and postoperative functional outcomes were collected and analyzed. The functional outcomes of SER ankle fractures were assessed postoperatively at 1-year face-to-face follow-up using the foot and ankle outcome score (FAOS) and American Orthopedic Foot and Ankle Society ankle hindfoot score and by 2 experienced orthopedic physicians. Relevant data were analyzed using SPSS version 22.0 by Chi-square or t-test. RESULTS: During the study period, there were 371 ankle fractures. Among them, 190 (51.2%) were SER patterns with 69 (36.3%) combined with dislocations. Compared with the no-dislocation group, the dislocation group showed no statistically significant differences in gender, age composition, fracture type, diabetes, or smoking history, preoperative waiting time, operation time, and length of hospital stay (all p > 0.05), but a significantly higher Lauge-Hansen injury grade (p < 0.001) and syndesmotic screw fixation rate (p = 0.033). Moreover, the functional recovery was poorer, revealing a significantly lower FAOS in the sport/rec scale (p < 0.001). Subgroup analysis showed that among SER IV ankle fracture patients, FAOS was much lower in pain (p = 0.042) and sport/rec scales (p < 0.001) for those with dislocations. American Orthopedic Foot and Ankle Society ankle hindfoot score revealed no significant difference between dislocation and no-dislocation patients. CONCLUSION Dislocation in SER ankle fractures suggests more severe injury and negatively affects functional recovery, mainly manifested as more pain and poorer motor function, especially in SER IV ankle cases.
Humans ; Ankle Fractures/physiopathology* ; Male ; Female ; Retrospective Studies ; Adult ; Middle Aged ; Supination ; Aged ; Young Adult ; Rotation ; Joint Dislocations/surgery* ; Fracture Fixation, Internal/methods* ; Adolescent ; Recovery of Function ; Treatment Outcome

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

Objective To investigate the role of poly(rC)-binding protein 1(PCBP1)in cadmium(Cd)-induced ferroptosis in mouse neuroblastoma Neuro-2a(N2A)cells.Methods N2A cells were exposed to a concentration gradient of CdCl?(0,1,2,4 μmol/L)for 72 h.Cell viability was assessed by trypan blue staining.Western blotting was employed to detect the expression of ferroptosis-related proteins(GPX4,HMOX1,ACSL4)and PCBP1.Intracellular Fe2? level and lipid peroxidation were detected using FerroOrange and BODIPY581/591 C11 probes,respectively.Ferrostatin-1(Fer-1),a ferroptosis inhibitor,was applied to confirm the critical role of ferroptosis in Cd-induced cytotoxicity.Molecular docking was performed to elucidate the interaction between PCBP1 and ferritin,as well as the binding sites of Cd2?.PCBP1 overexpression plasmid was further constructed for functional validation.Results Cd exposure suppressed cell viability in N2A cells in a dose-dependent manner(P<0.01),significantly down-regulated GPX4 expression(P<0.05),up-regulated HMOX1 expression(P<0.01),and induced Fe2? overload and lipid peroxidation(P<0.01).Molecular docking revealed that Cd2? directly bound to the KH2 domain of PCBP1 and then co-localized on the outer surface of ferritin heavy chain.Overexpression of PCBP1 markedly reversed Cd-induced Fe2? accumulation,GPX4 down-regulation,lipid peroxidation,and cell death.Conclusion Cd exposure disrupts PCBP1-mediated iron homeostasis via transcriptional suppression and competitive displacement of metal ions,and then synergistically drives Fe2? overload-triggered ferroptosis cascades,ultimately leading to neurotoxicity.Targeting PCBP1-mediated iron homeostasis can effectively mitigate Cd-induced neurotoxicity,and may serve as a novel therapeutic strategy.

Objective To explore the repair effect and mechanism of human amniotic mesenchymal stem cells(hAMSCs)on endometrial injury.Methods hAMSCs were isolated using a two-enzyme digestion and then cultured.The third-passage(P3)cells were harvested to detect the surface markers by flow cytometry and to identify their trilineage differentiation potentials.Eighteen nulliparous female SD rats(8～9 weeks old,weighing 250～280 g)were randomly divided into 3 groups(n=6):normal control group,model group,and hAMSCs group.A rat model of intrauterine adhesions(IUA)was established in SD rats by using curettage combined with lipopolysaccharide(LPS)infection.In 2 weeks after modeling,the hAMSCs group received a bilateral uterine horn transplantation of 0.2 mL hAMSCs(1.0×10? cells/mL),while the model group received a same volume of PBS into both uterine horns.All rats were sacrificed in 2 weeks after transplantation.HE and Masson staining was used to observe endometrial thickness and gland number as well as endometrial fibrosis area.RT-qPCR and Western blotting were performed to detect the mRNA and protein levels of TGF-β1,Smad3,Smad7,epithelial-mesenchymal transition(EMT)markers(E-cadherin,Vimentin),fibrosis factor α-SMA,and endometrial estrogen receptor(ER)and progesterone receptor(PR)in endometrial tissues.Results The obtained cells were identified as hAMSCs due to the characteristics of surface markers and differentiation potentials.Compared with the normal control group,the model group showed decreased endometrial thickness,reduced gland number,increased fibrosis area,and enhanced mRNA and protein levels of fibrosis-related factors TGF-β1,Smad3,Vimentin,and α-SMA(P<0.01),while down-regulation of fibrosis-inhibiting molecule Smad7,the EMT marker E-cadherin,and endometrial receptors ER and PR at both mRNA and protein levels(P<0.01).hAMSCs transplantation increased endometrial thickness and gland number,decreased fibrosis area,and down-regulated mRNA expression of the aforementioned fibrosis-related factors(P<0.01),and up-regulated the mRNA expression levels of Smad7,E-cadherin,ER,and PR(P<0.01).The hAMSCs group also exhibited obviously down-regulated protein levels of TGF-β1,Smad3,and α-SMA(P<0.05),while enhanced protein levels of Smad7 and PR(P<0.05).Conclusion Intrauterine transplantation of hAMSCs can promote the repair of endometrial injury,and inhibits endometrial EMT and fibrosis through the TGF-β1/Smad7 signaling pathway.

Objective To investigate the protective effects of secretomes released by three-dimensional cultured mesenchymal stem cells(MSCs)on neurons subjected to seawater immersion(SW)and stretch injury(SI),and to provide new insights into neuronal repair following SW combined with traumatic brain injury(TBI).Methods MSCs were cultured using the hanging drop method,and the conditioned medium(CM)containing MSCs secretomes was collected.A cellular model combining SW with SI was established using mouse hippocampal neuronal cells(HT22 cells).HT22 cells were randomly assigned to five groups:control,SI,SI+SW,SI+CM,and SI+SW+CM groups.Cell viability was assessed using the CCK-8 assay,apoptosis rate was measured by flow cytometry,cell migration ability was evaluated by scratch assay,and the expression levels of apoptosis-related proteins Bcl-2 and Bcl-2-associated protein(Bax),and ferroptosis-related proteins long-chain acyl-CoA synthetase 4(ACSL4)and cyclooxygenase-2(COX-2)were detected by Western blotting.Results Immersion in 15%seawater for 12 h significantly decreased HT22 cell viability(P<0.05).The CCK-8 assay indicated that cell viability in both the SI and SI+SW groups was significantly lower than that in control group after 12 h of treatment(P<0.05).Treatment with CM containing MSCs secretomes significantly increased cell viability in SI+CM group compared to SI group(P<0.0001),and in SI+SW+CM group compared to SI+SW group(P<0.001).Flow cytometry results revealed that the apoptosis rate in SI and SI+SW groups was significantly higher than that in control group(P<0.05 or P<0.001),while in SI+CM group was lower than that in SI group(P<0.05),and in SI+SW+CM group was lower than that in SI+SW group(P<0.05).Western blotting showed that compared to control group,SI and SI+SW groups exhibited reduced Bcl-2 expression level(P<0.01 or P<0.0001)and increased expression levels of Bax,ACSL4,and COX-2(P<0.01 or P<0.0001).Compared to SI group,the SI+CM group displayed increased Bcl-2 expression level(P<0.05)and decreased expression levels of Bax,ACSL4,and COX-2(P<0.05).Compared to SI+SW group,SI+SW+CM group exhibited increased Bcl-2 expression level(P<0.01)and decreased expression levels of Bax,ACSL4,and COX-2(P<0.01 or P<0.001).Scratch assay results demonstrated that at both 12 h and 24 h,the cell migration rate in SI and SI+SW groups was significantly lower than that in control group(P<0.01 or P<0.0001),while the migration rate in SI+CM group was significantly higher than that in SI group(P<0.0001 or P<0.01),and the migration rate in SI+SW+CM group was significantly higher than that in SI+SW group(P<0.0001).Conclusion Secretomes derived from MSCs cultured using the hanging drop method can alleviate neuronal damage caused by SW and TBI,potentially offering a therapeutic approach for SW combined with TBI.

Objective To explore the clinical efficacy and safety of immediate laparoscopic radical prostatectomy immediately following the diagnosis of locally advanced prostate cancer.Methods A retrospective analysis was performed for 63 patients with locally advanced prostate cancer who met the inclusion criteria diagnosed in The 1st People's Hospital of Qujing City,Yunnan Province from January 2018 to January 2023.All patients were diagnosed via ultrasound-guided transperineal prostate biopsy.The experimental group consisted of 37 patients who underwent immediate laparoscopic radical prostatectomy after pathological diagnosis,followed by postoperative adjuvant hormone therapy.The control group included 26 patients who first received 3 months of neoadjuvant hormone therapy before undergoing radical surgery,followed by adjuvant hormone therapy postoperatively.The two groups were compared in terms of surgical duration,intraoperative blood loss,length of hospital stay,duration of catheterization,positive surgical margin rate,rectal injury,positive lymph node rate,incidence of urinary fistula and lymphatic leakage,changes in PSA level,postoperative urinary control,biochemical recurrence and distant metastasis.Results In the control group,serum PSA levels,prostate volume,and clinical staging significantly decreased after neoadjuvant hormon therapy.The positive surgical margin rate in the experimental group was significantly higher than that in the control group,with a statistically significant difference(P<0.05).There were no statistically significant differences between the two groups in terms of surgical duration,intraoperative blood loss,length of hospital stay,duration of catheterization,rectal injury,positive lymph node rate,incidence of urinary fistula and lymphatic leakage(P>0.05).Follow-up at 18 to 36 months revealed no statistically significant differences between the two groups in terms of serum PSA levels at one month post-surgery,complete urinary control rate at six months post-surgery,and biochemical recurrence and distant metastasis at one and two years post-surgery(P>0.05).Conclusion Immediate laparoscopic radical prostatectomy following the diagnosis of locally advanced prostate cancer is a clinically safe and feasible treatment option.Noadjuvant hormone therapy reduces tumor staging,lowers the positive surgical margin rate,significantly decreases prostate volume,and provides greater operational space without increasing surgical risks.

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.

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.