low transit constipation （STC） is a common functional intestinal disorder caused by impaired colonic transit function， characterized by reduced bowel movement frequency， hard stools， and difficulty in defecation. The mitogen-activated protein kinase （MAPK） signaling pathway， which mainly includes extracellular signal-regulated kinase （ERK）， c-Jun N-terminal kinase （JNK）， and p38 subtypes， plays a critical regulatory role in the occurrence and development of STC. This paper systematically reviews the multiple pathogenic mechanisms of the MAPK signaling pathway in STC and the research progress of traditional Chinese medicine （TCM） intervention.At the mechanistic level， the MAPK signaling pathway promotes the progression of STC through the following links：（1） Activation of p38 upregulates the expression of aquaporin 3 （AQP3）/AQP4 in the colon， leading to excessive reabsorption of water in the intestinal lumen； （2） It forms a positive feedback loop with nuclear factor-κB （NF-κB） to maintain low-grade intestinal inflammation， releases inflammatory factors such as tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）， and inhibits smooth muscle contraction； （3） Overactivation of p38 downregulates the expression of occludin and mucin 2 while upregulates the expression of claudin-2， thereby disrupting the mucosal barrier； （4） The JNK/p38 signaling pathway activates the caspase cascade to induce apoptosis of intestinal epithelial cells， neurons， and interstitial cells of Cajal； （5） Abnormal ERK signaling and excessive activation of p38/JNK inhibit intestinal smooth muscle contraction and reduce 5-hydroxytryptamine secretion， ultimately resulting in impaired colonic transit function.At the intervention level， TCM compound formulas and single herbs have been proven to improve STC by regulating the MAPK signaling pathway. Their effects are syndrome type-dependent：yin-nourishing formulas （Zengye Chengqi Tang， Tongbian Tang） mainly regulate the ERK/AQP axis； yang-warming formulas （Jichuan Jian） target both ERK/JNK and anti-apoptosis； heat-clearing formulas （Sanren Tang） focus on p38/NF-κB anti-inflammation. A single drug can simultaneously cover multiple aspects including water metabolism， inflammation， barrier function， apoptosis， and intestinal motility.Current relevant studies still have limitations such as mechanisms mostly remaining at the correlational level and a lack of disease-syndrome integrated research models. Future studies should combine specific inhibitors or gene knockout to identify core targets， establish disease-syndrome integrated STC models， and use network pharmacology and molecular docking techniques to deeply analyze the fine mechanism of “component-target-phenotype”， so as to provide high-quality evidence for the precise regulation of the MAPK signaling pathway by TCM in the intervention of STC.

Definitive chemoradiotherapy (dCRT) has become a cornerstone in the treatment of locally advanced esophageal cancer; however, local control remains suboptimal, and persistent lesions or locoregional recurrences after treatment are not uncommon. For patients without distant metastases but with local failure, whether surgical intervention can still offer curative potential remains a major clinical dilemma. Salvage esophagectomy (SE) offers potential long-term survival for selected patients, but this procedure is performed in the context of severe fibrosis, impaired local blood supply, and obscured anatomical planes following chemoradiotherapy, resulting in significantly higher perioperative risk compared to primary esophagectomy. Consequently, controversies exist regarding patient selection, preoperative restaging, choice of surgical approach, extent of lymphadenectomy, gastrointestinal reconstruction, and perioperative management. In recent years, with the refinement of restaging modalities such as PET/CT, the accumulation of experience in high-volume centers, and emerging evidence from clinical studies, the clinical role of SE has gradually shifted from a "high-risk salvage measure" to a "selective curative strategy aimed at achieving long-term survival in carefully selected patients". Nevertheless, standardized guidelines for patient selection, technical approaches, and perioperative management are still lacking. Based on current evidence and clinical experience, experts organized by the Integrated Esophageal Cancer Committee of Chinese Anti-Cancer Association systematically reviewed key issues regarding SE, including its definition, indications, preoperative evaluation, choice of surgical approach, lymphadenectomy, gastrointestinal reconstruction, and perioperative management, and formulated a Chinese expert consensus. This consensus aims to provide guidance for standardized assessment, appropriate referral, individualized surgical decision-making, and optimized perioperative management of patients with locoregional failure after dCRT. Ultimately, this will increase the likelihood of R0 resection, reduce the risk of severe complications, and promote the safer, more judicious, and standardized implementation of SE in high-risk scenarios.

AIM To investigate the effects of volatile oil from Acorus tatarinowii Schott(A.tatarinowii)on neuroinflammation in a rat model of tic disorders.METHODS The SD rats were randomly divided into the blank group(8 rats)and the model group(40 rats).The rat models of tic disorders established successfully by intraperitoneal injection of iminodiapropionitrile(IDPN)were further divided into the model group,the tiapride group and the high-dose,moderate-dose and low-dose A.tatarinowii volatile oil groups,with 8 rats in each group.The 4-week intragastric treatment of respective drug was initiated the next day after the completion of modeling,and normal saline was dosed upon the blank group and the model group,during which the rats' behavioral changes were assessed by stereotyped behavior and motor behavior score every week.After the administration,the rats had their morphological changes of striatal neurons observed by Nissl staining;their levels of TGF-β,IL-10,TNF-αand IL-1β in serum and striatum detected by ELISA;their striatal protein expressions of CX3CL1 and CX3CR1 detected by Western blot and immunohistochemistry;and their striatal expressions of M1,M2 microglia marker proteins CD86,CD206,SYN and PSD-95 detected by immunofluorescence co-staining.RESULTS Compared with the model group,the A.tatarinowii volatile oil groups demonstrated improved twitch-like behavior;decreased scores of motor behavior and rigid behavior(P＜0.01);alleviated damage of Nissl bodies in neurons;increased serum and striatum levels of TGF-β and IL-10(P＜0.05,P＜0.01);decreased levels of TNF-α and IL-1β(P＜0.01);decreased striatal protein expressions of CX3CL1 and CX3CR1(P＜0.01);increased protein expressions of PSD95 and SYN(P＜0.05,P＜0.01);and decreased CD86/Iba1(P＜0.01)and increased CD206/Iba1(P＜0.01)in terms of the fluorescence intensity.CONCLUSION A.tatarinowii volatile oil contributes an anti-tic effect and improves the neuroinflammation in the brain of the rat model of tic disorders by promoting the transformation of microglia into M2 type via CX3CL1/CX3CR1 signal axis.

We reported the clinical manifestations,radiographic characteristics and prognosis of 1 case with Mycolicibacterium wolinskyi pulmonary disease,and provided a comprehensive literature review on this disease.Using"M.wolinskyi"OR"Mycobacterium wolinskyi"OR"Mycolicibacterium wolinskyi"as search term in PubMed database,CNKI and Wanfang database up to August 26 2023,40 reports were retrieved.32 cases from the literature and 1 case of our institution were used for review.A 59-year-old female presented intermittent hemoptysis since 2015.She was diagnosed with tuberculosis and clinical symptoms continued after anti-tuberculosis treatment.After multiple cultures of mycobacterium sputum and species identification in our hospital,M.wolinskyi was finally identified.She was diagnosed with M.Wolinski pulmonary disease according to clinical symptoms,computed tomography findings as well as bacteriological examinations.Combination therapy with Azithromycin,Moxifloxacin hydrochloride and Amikacin were administered based on antimicrobial susceptibility testing.Mycobacterium sputum culture became negative after 1 month treatment and kept negative,and the patient continued this combination therapy for 12 months after first culture negative.M.wolinskyi disease is exceedingly rare in medical institutions,and clinical symptoms are different depending on different location.Most cases were infected with skin,soft tissue or bone tissue infection after trauma or surgery,and a few cases were bloodstream infection.Most patients could have a good prognosis after proper treatment.M.wolinskyi disease is rare and clinically atypical,which may lead to long-term misdiagnosis.With the increase of aged or immunosuppressed population,the diagnosis and treatment of these rare non-tuberculous mycobacterial infections deserve more attention.

Aim To investigate the effect of exosomes derived from bone marrod-derived mesenchymal stem cells(BMSCs)on dexamethasone-induced C2C12 muscular canal atrophy.Methods(1)C57BL/6J mouse bone marrow mesenchymal stem cells were isola-ted and cultured by whole bone marrow adhesion meth-od.(2)Extraction and identification of BMSCs EXOs were performed.(3)Myogenic differentiation of C2C12 cells was carried out.(4)The successfully differentia-ted myotubes were divided into the control group(cul-tured in 2％equine serum medium for 48 h),dexam-ethasone group(dexamethasone,DEX,10 μmol·L-1 concentration of DEX interfered with myotubes for 48 h),and exosomes group(exosomes,EXOs,interfered with myotubes for 48 h),exosome inhibitor group(exo-somes extracted from BMSCs after 10 μm GW4869 in-tervention,interfered with myotubes for 48 h).48 h later,the morphology and diameter of muscle tubes were observed and measured by microscope.Cell via-bility of each group was detected by CCK-8 method.The expression levels of atrogin-1 and MuRF-1,myo-genic differentiation antigen(MYOD)in each group were detected by Western blot.Results BMSCs were long spusiform,and BMSCS-EXOS showed a circular bilayer structure under transmission electron microsco-py,with a diameter of about 200 nm.CD9,CD63 and CD81 were highly expressed.Compared with the con-trol group,cell activity in DEX group decreased(P＜0.01),diameter of myotubes decreased(P＜0.01),expressions of atrogin-1(P＜0.05)and MuRF-1(P＜0.01)were significantly up-regulated,and expression of MYOD(P＜0.01)was significantly down-regula-ted.Compared with the DEX group,cell activity in the BMSCs-EXOs group increased(P＜0.01),diameter of myotubes increased(P＜0.01),expressions of atrogin-1(P＜0.05)and MuRF-1(P＜0.01)were signifi-cantly down-regulated,and expression of MYOD(P＜0.01)was up-regulated.Compared with the BMSCs-EXOs group,cell activity of the BMSCs-EXOs(GW4869)group decreased(P＜0.05),diameter of myotubes decreased(P＜0.01),expressions of atrog-in-1(P＜0.05)and MuRF-1(P＜0.05)were up-regulated,and expression of MYOD(P＜0.01)was down-regulated.Conclusion Bone marrow mesen-chymal stem cell-derived exosomes(BM-MSCs-EXOs)inhibit dexamethasone-induced C2C12 muscle tube at-rophy.

OBJECTIVE To summarize the follow-up,survival time and treatment of a patients who received heart transplantation from a hepatitis B virus(HBV)-positive donor so as to raise the perception and awareness of pre-vention of hepatitis B after receiving the heart transplantation from a HBV-positive donor and extend the survival time of the patient.METHODS A patient who had new onset of hepatitis B after receiving heart transplantation from a HBV-positive donor and was treated in infectious diseases department of Zhongnan Hospital of Wuhan Uni-versity in Mar.2021 was enrolled in the study.The clinical data,including the main clinical symptoms,medication and treatment history,individual history,major positive signs and treatment outcomes,were retrospectively ana-lyzed.The process of diagnosis and treatment was analyzed and was further discussed in combination with litera-ture search.RESULTS The patient was treated with immunosuppression and anti-HBV therapy for 11 months after the heart transplantation,and the patient had anorexia,fatigue,diarrhea,and skin icteric sclera in the current month of withdrawal of drug therapy.The patient was admitted to the hospital and was finally diagnosed with a-cute hepatic failure,acute hepatitis B,acute renal failure,septic shock,heart transplantation and gastrointestinal hemorrhage.The patient died due to ineffective treatment.CONCLUSIONS The patient with new onset of HBV in-fection who receives organ transplantation and takes a long-term use of immunosuppressors may have severe con-sequences such as new onset of hepatitis B and acute hepatic failure.It is necessary to attach great importance to and take comprehensive measures for the prevention of new onset HBV infection in the donor after the organ transplantation,stick to the long-term reexamination of HBV infection-related indexes and maintain the antiviral therapy as long as possible(at least 1 year),which may facilitate the protection of the patient from HBV infec-tion-related adverse events and help to extend the survival time of the patient after the organ transplantation.

Objective:To assess the impact of urban-rural health insurance integration on the non-agricultural employment of rural labor in China.Methods:Using CHFS data(2011-2019)and a DID model,this study analyzed the impact on non-agricultural employment probability and quality(wage income,job stability)and examined the effect of different integration models.Results:The integration of urban and rural health insurance significantly increases the probability and quality of non-agricultural employment among rural labor.This effect operates through three key mechanisms:easing household liquidity constraints,improving health-related human capital,and expanding job search scope.Moreover,the"unified urban-rural tier"model proves more effective than the"one-system-multi-tiers"model in promoting non-agricultural employment and enhancing job quality.Conclusion:The integration positively contributes to improving rural labor allocation efficiency and mobilizing surplus rural labor capacity.Policy recommendations include accelerating the adoption of the"unified urban-rural tier"model and further refining the urban-rural resident health insurance system.

Objective:To assess the impact of elderly medical and nursing services pilots on the health of the elderly and its differentiated effects.Methods:Using five-period unbalanced panel data from China Longitudinal Aging Social Survey conducted between 2014 and 2023,the study employed a PSM-DID method to analyze changes in the health status of the elderly before and after the reform.Results:The pilots significantly improved the health status of the elderly,with the policy's effects most notably enhancing their psychological health.The elderly groups at a disadvantage in terms of resources,such as those with advanced age,low educational levels,or living apart from their children,can obtain greater mental health benefits from the pilots.The long-term care insurance and elderly medical care services pilots formed a policy synergy,but the implementation of multiple overlapping policies may attenuate the pilot's effects.Conclusions:The pilots have yielded initial results,but there is still considerable room for improvement.It is recommended to actively promote the integration of regional medical and nursing resources,precisely meet the needs of disadvantaged the elderly groups,and strengthen interdepartmental collaboration and information sharing.

Aim To study whether intravenous injec-tion of miR-129-3p mimetic(agomir)can resist bone loss caused by hind limb disuse,and to provide new i-deas for preventing bone loss in microgravity environ-ment.Methods Forty-eight C57BL/6J male mice were randomly divided into the control group(CON),tail suspension model group(TS),tail suspension+miR-129-3p agomir administration group(miRNA)and tail suspension+miR-129-3p negative sequence agomir control group(NC).The miRNA group was given 4 mg·kg-1 miR-129-3p agomir by intravenous injection into the medial canthus twice a week.The NC agomir group were consistent with those in the miR-129-3p agomir group,and the CON and TS groups were given only equal volumes of normal saline.After four weeks,all mice were sacrificed and samples were collected.Micro-CT scan of femur,three-point femur bending test,serum bone metabolism index detection,oxidative stress index detection and osteogenesis-related protein expression analysis in bone tissue were per-formed.Results After four weeks,the number of tra-becular bone in the TS group was significantly re-duced,and Tb.BMD,Tb.Th,Tb.N,Tb.BS/TV and Tb.BV/TV were significantly lower than those in the CON group(P＜0.01).While Tb.Sp TS group was significantly higher than the CON group(P＜0.05),the maximum load and flexural strength of the femur significantly decreased(P＜0.01),the content of ser-um bone formation index PINP was significantly lower than that of the CON group(P＜0.01),and the con-tent of bone resorption index CTX-I was significantly higher than that of the CON group(P＜0.01),the content of serum oxidative damage indexes 8-iso-PGF2α and 8-OHdG significantly increased(P＜0.01),and the expression of osteogenesis-related pro-teins in bone tissue markedly decreased(P＜0.01).However,the increase or decrease of all indexes in miRNA group was significantly lower than that in TS group.Conclusions miR-129-3p mimetic can signifi-cantly reduce bone loss caused by hind limb disuse.This experiment provides a new idea and method for preventing bone loss in microgravity environment.

Objective To evaluate the efficacy,safety and economy of vonoprazan in the treatment of post-endoscopic submucosal dissection(ESD)ulcer by rapid health technology assessment method,and to provide reference for clinical treatment decision.Methods PubMed,Cochrane Library,Embase,ScienceDirect,CNKI,WanFang Data databases and the official website of health technology assessment(HTA)agency were electronically searched to collect HTA reports,systematic reviews/Meta-analysis and pharmacoeconomic studies of vonoprazan in the treatment of post-ESD ulcer from inception to July 31,2024.Two researchers independently screened literature,extracted data,and comprehensively analyzed the results of the included literature on the basis of literature quality evaluation.Results A total of 8 studies were included,all were systematic reviews/Meta-analysis.In terms of effectiveness,compared with proton pump inhibitors(PPI),vonoprazan significantly increased the overall ulcer healing rate after ESD and more rapid reduction of ulcer area(P<0.05).The results of subgroup analysis showed that there was no significant difference in ulcer healing rate between vonoprazan and PPI treatment at 4 or 8 weeks after ESD(P>0.05).Vonoprazan significantly increased the rate of postoperative ulcer reduction in H.pylori positive patients compared with PPI(P<0.05).In terms of safety,compared with PPI,vonoprazan reduced the incidence of overall adverse events rate(P<0.05).The difference in the incidence of delayed bleeding and ulcer perforation between vonoprazan and PPIs showed no statistically significant difference.(P>0.05).Conclusion Vonoprazan demonstrated favorable efficacy and safety in the treatment of ESD ulcers,and further economic studies are warranted.