Functional constipation （FC） is a common functional disorder of the intestines， mainly characterized by reduced bowel movement frequency， difficulty in defecation， a sensation of incomplete evacuation， and hard stools， which severely affect patients’ quality of life. Research indicates that the pathogenesis of FC is closely related to gut microbiota dysbiosis and abnormal bile acid secretion. Bile acids， as endogenous natural laxatives， promote bowel movements by enhancing colonic secretion and regulating intestinal motility； meanwhile， gut microbiota influence colonic transit function by regulating the enteric nervous system， immune system， and their metabolic products. Based on an overview of the relationship between gut microbiota and bile acid metabolism， this article systematically reviews the current research status on the mechanisms of traditional Chinese medicine （TCM） in treating FC by regulating the balance of the gut microbiota-bile acid axis. It is found that single Chinese medicinal herbs （such as Atractylodes macrocephala）， isolated compounds （such as Platycodon grandiflorum polysaccharides）， herbal formulas （such as Shanger huang pill）， acupuncture， and moxibustion can up-regulate the abundance of beneficial bacteria， reshape the microbial structure， correct bile acid metabolism， and activate the Takeda G-protein receptor 5/farnesoid X receptor pathway to treat FC.

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.

Objective To analyze the association between lifestyle and the risk of type 2 diabetes(T2D)among adult residents.Methods The data was sourced from the Shanghai Suburban Adult Cohort and Biobank.A total of 42 096 adult residents who had not developed T2D were recruited from four districts of Shanghai(Songjiang,Jiading,Minhang,and Xuhui)between 2016 and 2019.The follow-up ended on Feb 28,2023.A structured questionnaire was used to collect information on six lifestyle-related items,including smoking,alcohol consumption,BMI,waist circumference(WC),physical activity,and diet.The unhealthy lifestyle scores(UHLS)were calculated by counting the number of all the unhealthy lifestyle items,with a range of 0-6.New-onset T2D events diagnosed by physicians were obtained through the medical information system.Cox proportional hazards regression model and restricted cubic spline model were utilized to evaluate the association between unhealthy lifestyles and the risk of T2D incidence.Results About 28.1%of the participants led 4-6 unhealthy lifestyles.A total of 1 752 new T2D cases were identified during 218 513.4 person-years of follow-up.Analysis of single unhealthy lifestyle showed that abnormal WC(HR=1.5,95%CI:1.4-1.7)and abnormal BMI(HR=1.3,95%CI:1.2-1.5)were associated with an increased risk of T2D.Compared with individuals with a UHLS of 0-1,those with a UHLS of 3 and 4-6 had 30%(95%CI:1.1-1.6)and 50%(95%CI:1.2-1.8)higher risks of T2D,respectively.Each additional unhealthy lifestyle was associated with a 10%increase in T2D incidence risk(HR=1.1,95%CI:1.1-1.2).Conclusion The risk of T2D in adult residents increases with the cumulative number of unhealthy lifestyles.Adult residents with abnormal WC or BMI,or have three or more unhealthy lifestyles accumulated,will increase the risk of new-onset T2D.

Aim To explore the possible regulatory effect of leptin on acyl-CoA synthetase long chain fami-ly member ACSL5 and their effect on migration and in-vasion of breast cancer cell,and to explore the underly-ing mechanism.Methods The expression of leptin receptor was detected by immunofluorescence assay.The migration and invasion ability of MCF-7 cells were detected by wound healing assay and Transwell assay respectively.The downstream target gene of leptin was analyzed by PCR microarray data.The expression of ACSL5 in breast cancer and its correlation with the staging and prognosis of breast cancer patients were as-sessed uing bioinformatics methods.The expression of ACSL5 in MCF-7 cells treated with different concentra-tions of leptin was detected using real time fluorescence quantitative polymerase chain reaction(RT-qPCR).Overexpressing ACSL5 was constructed by lentiviral transfection;the expressions of EMT related proteins,AMPK-α and p-AMPK-α were detected by Western blot.Results Leptin promoted breast cancer cell mi-gration and invasion and EMT.ACSL5 was significant-ly low expressed in breast cancer and related to progno-sis.Leptin downregulated the expression of ACSL5 through OBR.Leptin activated AMPK pathway to downregulate ACSL5 and promote migration,invasion and EMT of breast cancer cells.Conclusions Leptin may promote the migration,invasion and EMT of breast cancer by downregulating ACSL5 through activating AMPK pathway.

Objective:To investigate the neuroprotective effect of non-invasive vagus nerve stimulation(nVNS)on traumatic brain injury(TBI).Methods:Male SD rats were used to prepare controlled cortical impact(CCI)rat mod-el.nVNS treatment was performed.The motor function of rats was detected by beam walking test.The water content of rats was evaluated by the dry-wet ratio of rat brain tissue.The content of lactate dehydrogenase(LDH)in cerebrospinal fluid was detected by commercial kit.The expression of bain-derived neurotrophic factor(BDNF)and nerve growth fac-tor(NGF)mRNA in rat cortex was detected by RT-qPCR.Results:After nVNS stimulation,CCI rats significantly im-proved the neurological function deficit,improved the motor ability,decreased the cerebral water content,decreased the level of LDH in cerebrospinal fluid,and upregulated the expression of BDNF and NGF mRNA in cortex.Conclusion:nVNS has a neuroprotective effect on TBI rats,and its mechanism may be related to the increased expression of BDNF and NGF.

Objective:To investigate the neuroprotective effect of non-invasive vagus nerve stimulation(nVNS)on traumatic brain injury(TBI).Methods:Male SD rats were used to prepare controlled cortical impact(CCI)rat mod-el.nVNS treatment was performed.The motor function of rats was detected by beam walking test.The water content of rats was evaluated by the dry-wet ratio of rat brain tissue.The content of lactate dehydrogenase(LDH)in cerebrospinal fluid was detected by commercial kit.The expression of bain-derived neurotrophic factor(BDNF)and nerve growth fac-tor(NGF)mRNA in rat cortex was detected by RT-qPCR.Results:After nVNS stimulation,CCI rats significantly im-proved the neurological function deficit,improved the motor ability,decreased the cerebral water content,decreased the level of LDH in cerebrospinal fluid,and upregulated the expression of BDNF and NGF mRNA in cortex.Conclusion:nVNS has a neuroprotective effect on TBI rats,and its mechanism may be related to the increased expression of BDNF and NGF.

Objectives:To investigate the expression and clinical prognostic implication of secreted frizzled-related protein 4(SFRP4)in the peripheral blood of patients with dilated cardiomyopathy(DCM)and its.Methods:A total of 259 consecutive patients diagnosed with DCM who were admitted to the Cardiac Center of Zhongshan Hospital,Fudan University,from January 2017 to January 2019 were selected for the DCM group.Additionally,84 individuals who underwent health examinations and echocardiography at our hospital during this period,confirmed to be free of cardiovascular diseases,were selected as the control group.Peripheral serum samples were collected from both groups,and serum SFRP4 levels were measured using enzyme-linked immunosorbent assay(ELISA).The correlation between SFRP4 levels and DCM severity,as well as its predictive value for DCM prognosis,were analyzed.Results:Compared to the control group,the serum SFRP4 levels in the DCM group were significantly elevated([28.54±10.25]ng/ml vs.[52.70±19.74]ng/ml,P<0.05).The DCM group was randomly divided into a training set and a validation set in a 2:1 ratio.Multivariate logistic regression analysis in the training set revealed that serum SFRP4 levels were independently associated with all-cause mortality in DCM patients(OR=1.06,95% CI:1.03-1.10,P<0.001).We further evaluated the model's predictive performance with the receiver operating characteristic(ROC)curves(area under curve>0.8),calibration curves,and decision curve analysis,results indicated that the predictive model containing serum SFRP4 levels showed good performance on predicting all-cause mortality in DCM patients.Kaplan-Meier survival curve analysis demonstrated that during a median follow-up of 33.5(11.0,49.0)months,DCM patients with high peripheral blood SFRP4 levels(≥75th percentile)had a significantly higher incidence of all-cause mortality compared to those with low levels(<75th percentile)(28.81% vs.16.57%,P=0.02).Conclusions:The level of SFRP4 in the peripheral blood of DCM patients is significantly elevated,and peripheral serum SFRP4 levels have potential prognostic value for predicting the all-cause mortality in DCM patients.

Objective:This study aimed to evaluate the application effect of opioid-free anesthesia(OFA)in modified radical mastectomy for breast cancer.Methods:80 patients undergoing unilateral modified radical mastec-tomy were randomly divided into two groups:general anesthesia group(G group)and OFA group(O group).The G group received general anesthesia with opioid drugs and a laryngeal mask,while the O group received general anes-thesia with intravenous lidocaine combined with thoracic paravertebral nerve block and a laryngeal mask.The average arterial pressure(MAP)and heart rate(HR)of the patients were recorded at the time of admission(T0),induction(T1),start of surgery(T2),gland resection(T3),and admission to the recovery room(T4).The surgical time,awakening time,ex-tubation time,and getting out of bed time were recorded.The VAS score at 2 hours(T5),6 hours(T6),and 12 hours(T7)after surgery,as well as the systemic immune-inflammatory index(SII)before surgery(T8),6 hours after surgery(T9),and 12 hours after surgery(T10)were recorded.The occurrence of postoperative nausea and vomiting(PONV)and post-mastectomy pain syndrome(PMPS)were recorded.The occurrence of adverse events such as poor nerve block effect,pneumothorax,hematoma,and local anesthetic toxicity were also recorded.Results:The MAP and HR of the O group were more stable than those of the G group during surgery(P＜0.05).The awakening time,extubation time,and getting out of bed time in the O group were earlier than those in the G group(P＜0.05).The VAS and SII values after surgery were significantly lower in the O group than in the G group(P＜0.05).The incidence of PONV was also signifi-cantly decreased(P＜0.05).In addition,no adverse events such as pneumothorax,hematoma,or local anesthetic toxic-ity occurred in the O group.Conclusion:Pioid-free anesthesia is safe and effective in modified radical mastectomy for breast cancer,shortening recovery time,time to first flatus,and time to ambulation,while alleviating postoperative pain,systemic inflammatory response,perioperative hemodynamic fluctuations,and the incidence of postoperative nau-sea and vomiting.

Lens injury is an important etiological factor in the reduction of visual function following ocular trauma.Currently, there are no clear standards for the classification of lens injury, and comprehensive diagnostic tools are lacking.This deficiency leads to numerous controversies and challenges in critical areas, such as diagnosis and preoperative evalution, timing of surgery, surgical strategy, and assessment of postoperative prognosis.Tomographic imaging technology, such as computed tomography, magnetic resonance imaging, optical coherence tomography, has introduced a new dimension to the evaluation of lens injury, which is crucial for assessing the transparency, texture, location, morphology, and integrity of the lens, as well as the zonules and nearby intraocular structures.However, the use of tomographic imaging technology is somewhat limited due to the limitations of relying on a single method.With the ongoing advancement of imaging technologies and the rapid development of big data and artificial intelligence, tomographic imaging will become an increasingly essential tool in the future management of lens injury.Our expert group reviewed the epidemiological characteristics and classification of lens injury and the major challenges currently faced in the diagnosis and treatment of lens injury, and provided expert recommendations mainly focusing on the application, shortcomings and limitations of current tomographic imaging technology in the diagnosis and treatment of lens injury, and future development directions.

Objective To analyze the association between lifestyle and the risk of type 2 diabetes(T2D)among adult residents.Methods The data was sourced from the Shanghai Suburban Adult Cohort and Biobank.A total of 42 096 adult residents who had not developed T2D were recruited from four districts of Shanghai(Songjiang,Jiading,Minhang,and Xuhui)between 2016 and 2019.The follow-up ended on Feb 28,2023.A structured questionnaire was used to collect information on six lifestyle-related items,including smoking,alcohol consumption,BMI,waist circumference(WC),physical activity,and diet.The unhealthy lifestyle scores(UHLS)were calculated by counting the number of all the unhealthy lifestyle items,with a range of 0-6.New-onset T2D events diagnosed by physicians were obtained through the medical information system.Cox proportional hazards regression model and restricted cubic spline model were utilized to evaluate the association between unhealthy lifestyles and the risk of T2D incidence.Results About 28.1%of the participants led 4-6 unhealthy lifestyles.A total of 1 752 new T2D cases were identified during 218 513.4 person-years of follow-up.Analysis of single unhealthy lifestyle showed that abnormal WC(HR=1.5,95%CI:1.4-1.7)and abnormal BMI(HR=1.3,95%CI:1.2-1.5)were associated with an increased risk of T2D.Compared with individuals with a UHLS of 0-1,those with a UHLS of 3 and 4-6 had 30%(95%CI:1.1-1.6)and 50%(95%CI:1.2-1.8)higher risks of T2D,respectively.Each additional unhealthy lifestyle was associated with a 10%increase in T2D incidence risk(HR=1.1,95%CI:1.1-1.2).Conclusion The risk of T2D in adult residents increases with the cumulative number of unhealthy lifestyles.Adult residents with abnormal WC or BMI,or have three or more unhealthy lifestyles accumulated,will increase the risk of new-onset T2D.