Increasing evidence has underscored the significance of post-stroke alterations along gut-brain axis, while its role in pathogenesis and treatment of ischemic stroke (IS) remains largely unexplored. This study aimed to elucidate the therapeutic effects and action targets of Panax notoginseng saponins (PNS) on IS and explore a novel pathogenesis and treatment strategy of IS via profiling the microbial community and metabolic characteristics along gut-brain axis. Our findings revealed for the first time that the therapeutic effect of PNS on IS was microbiota-dependent. Ischemia/reperfusion (I/R) modeling significantly down-regulated Lactobacilli in rats, and PNS markedly recovered Lactobacilli, particularly Lactobacillus reuteri (L.Reu). Metabolomics showed a significant reduction in serum histidine (HIS) in clinical obsolete IS patients and rehabilitation period I/R rats. Meanwhile, the L.Reu colonization in I/R rats exhibited significant neuroprotective activity and greatly increased HIS in serum, gut microbiota, and brain. Moreover, exogenous HIS demonstrated indirect neuroprotective effects through metabolizing to histamine. Notably, vagus nerve severance in I/R rats was performed to investigate HIS's neuroprotective mechanism. The results innovatively revealed that PNS could promote HIS synthesis in gut by enhancing L.Reu proportion, thereby increasing intracerebral HIS through peripheral pathway. Consequently, our data provided novel insights into HIS metabolism mediated by L.Reu in the pathogenesis and treatment of IS.

Objective To evaluate the effect of Helicobacter pylori(H.pylori)infection on colorectal adenoma(CRA)recurrence after polypectomy and to study other potential prognosis factors associated with CRA recurrence.Methods This single-centered retrospective cohort study included 808 patients with CRA who underwent colonoscopy,polypectomy,and gastroscopy between January 2005 and October 2022.The patients were classified into three groups based on H.pylori infection status:persistently negative(group A,n=626),initially positive but turned negative(group B,n=141),and persistently positive(group C,n=41).The CRA recurrence and high-risk CRA or colorectal cancer(CRC)occurrence were assessed,and potential prognosis factors for recurrence were analyzed.Results During a median follow-up period of 1.6(1.1,2.4)years,the recurrence rate was 56.4%(456/808),including 124 cases(15.3%)of high-risk CRA/CRC[of which 5 cases(0.6%)were CRC]and 332 cases(41.1%)of low-risk CRA.The recurrence rates in the three groups were 55.4%(347/626),60.3%(85/141),and 58.5%(24/41),respectively,with no statistically significant difference(log-rank χ2=0.525,P=0.769).The high-risk CRA/CRC recurrence rates in the three groups were 14.9%(93/626),17.7%(25/141),and 14.6%(6/41),respectively,showing no significant intergroup differences(log-rank χ2=0.340,P=0.844).Multivariate analysis identified increasing age(HR=1.011,95%CI:1.002-1.021,P=0.020)and baseline high-risk CRA(HR=1.428,95%CI:1.183-1.724,P<0.001)as independent prognosis factors for CRA recurrence.Conclusions This study did not find a significant correlation between H.pylori infection and CRA recurrence after polypectomy.Increasing age and baseline high-risk CRA are prognosis factors for CRA recurrence.

Objective:To investigate the key technical aspects of laparoscopic anti-reflux surgery (LARS) in complex gastroesophageal reflux disease (GERD) with hiatal hernia (HH) and evaluate the feasibility and efficacy of reoperation.Methods:A retrospective analysis was conducted on 28 patients with complex GERD treated at Zhejiang Provincial People's Hospital from Feb 2020 to May 2024. Preoperative examinations were recorded, and surgical videos were reviewed to reconstruct operative time, critical intraoperative steps, complications, and management techniques. Postoperative follow-up via telephone and outpatient visits assessed symptom relief, complications, and medication use.Results:All 28 patients (4 robotic-assisted and 24 conventional laparoscopic surgeries) successfully underwent LARS, with an operative duration of (152.6±10.3) minutes and a postoperative hospital stay of (4.0±1.9) days. Large HH 9 cases, intraoperative bleeding 6 cases, pleural rupture 3 case, and esophageal perforation 1 case, preoperative diagnoses included short esophagus 2 cases and 7 redo surgeries. The overall recurrence rate was 11%. Postoperative complications occurred in 14%. The redo surgeries group achieved 71% symptom resolution. At 1-12 months of follow-up, 82% of patients were asymptomatic, and 82% discontinued proton pump inhibitor therapy.Conclusions:Complex scenarios requiring specialized techniques in LARS increase surgical difficulty and risks. Standardized management of the hernia sac, hiatal repair, neurovascular protection, identification of anatomical landmarks in reoperations, selection of biological mesh, and adhesiolysis may reduce recurrence rates and complication risks.

Background and Aims:Gamma-aminobutyric acid(GABA),the principal inhibitory neurotransmitter in the central nervous system,has been increasingly recognized in recent years as being closely associated with various liver-related diseases,such as hepatic encephalopathy,liver cirrhosis,and hepatocellular carcinoma.Abnormal GABA expression is strongly linked to pathological processes including cognitive impairment and neuroinflammation.Although numerous studies have investigated the mechanistic roles of GABA in neurological complications of liver disease,a systematic overview of the field's research trends,collaborative networks,and emerging hotspots remains lacking.This study employs bibliometric methods to comprehensively map the evolution and frontier topics in GABA and liver-related disease research from 2005 to 2024,aiming to inform future research planning and resource allocation in this area.Methods:English-language publications from 2005 to 2024 related to GABA and liver-related diseases were retrieved from the Web of Science Core Collection.Eligible articles were analyzed using VOSviewer,CiteSpace,and the R package"bibliometrix"to visualize and evaluate contributions by countries/regions,institutions,authors,and journals.Additional analyses included keyword clustering,co-citation analysis,and thematic evolution of research topics.Results:A total of 237 articles were included,contributed by 1 340 authors across 456 institutions in 47 countries,and published in 168 journals.The United States and China are leading contributors in this field.Although countries such as the United Kingdom and Italy had fewer publications,they demonstrated higher average citation counts,indicating strong research quality.Notably,Spain's Centro Investigación Principe Felipe and the research team led by Felipo Vicente exhibited high academic influence.Neurochemistry International and Hepatology were identified as core journals,with Hepatology having the highest impact factor(12.9).Keyword clustering revealed major research focuses including the regulatory role of GABA in the neural mechanisms of hepatic encephalopathy,the impact of liver-related metabolic disorders on neurotransmitter balance,the development and evaluation of GABA receptor-targeted therapeutics,and the function of the GABAergic system in the pathogenesis of hepatocellular carcinoma.As research deepens,the frequency of emerging keywords has diversified,with recent emphasis on terms such as"quality of life,""gene expression,"and"fatty liver disease,"reflecting a shift from fundamental mechanisms to clinical translation and interdisciplinary integration.Conclusion:The relationship between GABA and liver diseases has become a focal point of interdisciplinary research.Investigations have expanded from pathological mechanisms to therapeutic applications,with growing interest in GABA's roles in hepatic encephalopathy,metabolic dysregulation,and tumor progression.Future studies should explore the specific functions of GABA receptor subtypes,promote the development of precision-targeted therapies,and investigate novel mechanisms such as the gut microbiota-GABA metabolism-brain-liver axis to broaden the clinical and translational potential of GABA in neurological,metabolic,and oncological contexts.

ObjectiveTo employ Helicobacter hepaticus (H.hepaticus, H.h) to induce intestinal fibrosis in vitamin D receptor deletion (VDR^-/-) mice, thereby establishing a model of inflammatory bowel disease to investigate its pathological characteristics and underlying mechanisms. MethodsFive male WT and five male VDR^-/- mice were orally administered a suspension containing 2×10⁸ CFU of H.hepaticus (referred to as the WT+H.h group and the VDR^-/-+H.h group, respectively), with treatments occurring every other day for three administrations. Concurrently, two uninfected control groups were established, consisting of five WT and five VDR^-/- mice, which were administered an equivalent volume of PBS. Seven days after the final administration, the infection status of the mice was assessed, and their body weight was recorded weekly. At the 16^th week post-infection, the mice were dissected, and the length of the colon tissue was measured, with fecal moisture content analyzed. The colon tissue was partitioned into four parts: one for paraffin embedding for HE, alcian blue-periodic acid Schiff (AB-PAS), Masson's trichrome staining, and immunohistochemical analysis; one for DNA extraction to evaluate the colonization levels of H.hepaticus through real-time fluorescent quantitative polymerase chain reaction (RFQ-PCR), thereby assessing the impact of the infection; one for RNA extraction to analyze cytokine expression via reverse transcription-PCR (RT-PCR); and one for protein extraction to measure the expression levels of alpha smooth muscle actin (α-SMA) and interleukin (IL)-33 using Western blotting. Results All mice in the infected groups successfully were infected with H. hepaticus after three oral gavages. Compared to VDR^-/- control group, VDR^-/- mice exhibited significant weight loss (P<0.05), intestinal hemorrhage, and higher fecal water content after 16 weeks of H. hepaticus infection than the uninfected control group and the WT+H.h group (P<0.05). Compared to the WT+H.h group, HE staining of the VDR^-/-+H.h group showed inflammatory cell infiltration, AB-PAS staining revealed irregular atrophy of intestinal glands and reduced acini, and Masson staining showed increased collagen area. RT-PCR demonstrated that the transcription levels of inflammation and fibrosis-related genes, including IL-6, IL-33, tumor necrosis factor-α (TNF-α), and α-SMA (P < 0.000 1), were significantly upregulated in the colon tissues of VDR^-/-+H.h group. Additionally, immunohistochemical analysis and Western blotting showed that the protein expression levels of IL-33 and α-SMA were markedly increased (P<0.001) in the VDR^-/-+H.h group. ConclusionVDR^-/- mice infected with H.hepaticus exhibit more severe inflammatory responses, including mucosal inflammatory infiltration, impaired mucosal tissue function, and collagen deposition, indicating successful construction of the inflammatory bowel disease model. Further research suggests that VDR deficiency may exacerbate the intestinal fibrosis process associated with inflammatory bowel disease by affecting IL-33 expression.

Prescription optimization is a crucial aspect in the study of traditional Chinese medicine （TCM） compounds. In recent years， the introduction of mathematical methods， data mining techniques， and artificial neural networks has provided new tools for elucidating the compatibility rules of TCM compounds. The study of TCM compounds involves numerous variables， including the proportions of different herbs， the specific extraction parts of each ingredient， and the interactions among multiple components. These factors together create a complex nonlinear dose-effect relationship. In this context， it is essential to identify methods that suit the characteristics of TCM compounds and can leverage their advantages for effective application in new drug development. This paper provided a comprehensive review of the cutting-edge optimization experimental design methods applied in recent studies of TCM compound compatibilities. The key technical issues， such as the optimization of source material selection， dosage optimization of compatible herbs， and multi-objective optimization indicators， were discussed. Furthermore， the evaluation methods for component effects were summarized during the optimization process， so as to provide scientific and practical foundations for innovative research in TCM and the development of new drugs based on TCM compounds.

Objective To analyze the main epidemiological characteristics of fungal infection in this hospital in the past 7 years,and to provide reference for clinical treatment and prevention and control strategies of fun-gal infection.Methods The fungal data and clinical data of related patients isolated from clinical samples in Peking Union Medical College Hospital from early January 2018 to the end of May 2024 were selected,and the main epidemiological characteristics of fungal infection in this hospital were identified and described through multi-angle statistical analysis.Results A total of 4 479 patients with filamentous fungal infection were en-rolled.The proportion of male patients[57.5％(2 576/4 479)]was higher than that of female patients[42.5％(1 903/4 143)],mainly distributed in internal medicine,Intensive Care Unit(ICU)and emergency de-partment,among which internal medicine accounted for the highest proportion[50.0％(2 241/4 479)].About 90.0％of the specimens were from the lower respiratory tract,in addition to specimens from skin and soft tis-sue,tissue,ear and blood culture.In terms of seasonal distribution,there are more patients in winter.The fun-gi were mainly composed of Aspergillus,Mucor,Cerdosporium,Fusarium and Penicillium,among which As-pergillus was the most abundant,accounting for 74.6％of the total.Aspergillus fumigatus was the most a-bundant Aspergillus,accounting for 42.5％of the total Aspergillus(1 418/3 340).Among the related infec-tions caused by mold,Aspergillus was the most common in the lower respiratory tract,accounting for 76.8％.Among them,Aspergillus fumigatus accounted for the highest proportion(33.6％).98.6％of the molds infected the ear were Aspergillus,of which Aspergillus niger and Aspergillus terreus were the most common.Skin infections are mainly caused by Sporothrix schenckii,Trichophyton rubrum,Microsporum ca-nis.The results of in vitro drug sensitivity test showed that the four common Aspergillus isolated in this hos-pital were sensitive to voriconazole,and amphotericin B had better antifungal activity against Mucorales in vitro.Conclusion Based on the main epidemiological characteristics of fungal infections in this hospital,it is recommended that special attention be paid to the admission of patients in the respiratory department during the peak infection period in autumn and winter.In the treatment of fungal infections in different regions and on different body parts,attention should be paid to the differences in the distribution of bacterial species.

Objective This study aimed to explore the underlying mechanisms between parental neglect and depression of adolescents.Methods This study utilized data from the 2020 China Family Panel Studies(CFPS)and included 1902 adolescents aged 10～15.Correlation analysis,multivariable logistic regression,structural equation modeling,and the bootstrap method were employed to examine the relationships between parental neglect,social trust,and depressive symptoms in adolescents.Results This study found that the prevalence of depressive symptoms among adolescents was 10.9%.Parental neglect was associated with an increased risk of depressive symptoms(OR:1.772,95%CI:1.310～2.636),and social trust acted as a mediator between parental neglect and depressive symptoms(mediating effect:17.20%,P<0.001).Additionally,gender moderated the latter half of the mediation model(β:0.127,95%CI:0.016～0.236,P<0.001).Conclusion The experiences of parental neglect are closely related to higher levels of depressive symptoms among adolescents,with social trust serving as a mediating factor.This mediating effect of social trust is particularly significant among females.It is crucial to cultivate a supportive environment and develop a harmonious family atmosphere.

Background and Aims:Tumor deposits(TDs)may influence prognosis beyond the current 8th edition AJCC pTNM nodal classification in gastric cancer(GC).This study investigates the prognostic value of TD number and proposes an improved pN staging(mpN)that classifies patients with TD number>1 as pN3b.We validated the mpN staging against the 8th AJCC pN staging.Methods:A dual-center retrospective cohort study was performed,including 1 327 patients who underwent radical gastrectomy at Sun Yat-sen University Cancer Center(2011-2015;test cohort)and 340 patients from Guangdong Provincial People's Hospital(2015-2022;validation cohort).Patients were dichotomized into low-TD(≤1)and high-TD(>1)groups.Outcomes were overall survival(OS)and disease-free survival(DFS).Survival analyses used Kaplan-Meier curves,IPTW,and Cox regression.Predictive performance of staging systems was assessed by time-dependent ROC(tROC)/tAUC,concordance index(C-index)and Akaike information criterion(AIC).Results:TDs were present in 435/1 327(32.7%)in the test cohort.Presence of TD was associated with worse OS(IPTW-adjusted HR=2.69,95%CI=2.18-3.31,P<0.01)and DFS(HR=2.82,95%CI=2.32-3.42,P<0.01).In multivariable models,TD remained an independent adverse factor for OS(HR=1.65,95%CI=1.34-2.05;P<0.01)and DFS(HR=1.74,95%CI=1.43-2.11,P<0.01).Increasing TD number correlated with progressively poorer survival;X-tile identified>1 as an optimal cutoff,with high-TD patients showing markedly worse outcomes(OS:adjusted HR=3.65,95%CI=2.74-4.88;DFS:adjusted HR=3.74,95%CI=2.85-4.91;both P<0.01).Incorporation of TD number into the mpN staging(assigning TD>1 to pN3b)improved prognostic discrimination:in the test cohort 5-year OS tAUC was 0.746 for mpN vs.0.703 for AJCC pN(C-index 0.738 vs.0.721,AIC 5 805.27 vs.5 849.30);similar improvements were observed in the validation cohort.Conclusion:TD presence and number exert significant negative prognostic impact in GC.Classifying patients with TD number>1 as pN3b enhances prognostic accuracy.Routine reporting of TD counts and further prospective multicenter validation of mpN staging are warranted.

Objective This study aimed to explore the underlying mechanisms between parental neglect and depression of adolescents.Methods This study utilized data from the 2020 China Family Panel Studies(CFPS)and included 1902 adolescents aged 10～15.Correlation analysis,multivariable logistic regression,structural equation modeling,and the bootstrap method were employed to examine the relationships between parental neglect,social trust,and depressive symptoms in adolescents.Results This study found that the prevalence of depressive symptoms among adolescents was 10.9%.Parental neglect was associated with an increased risk of depressive symptoms(OR:1.772,95%CI:1.310～2.636),and social trust acted as a mediator between parental neglect and depressive symptoms(mediating effect:17.20%,P<0.001).Additionally,gender moderated the latter half of the mediation model(β:0.127,95%CI:0.016～0.236,P<0.001).Conclusion The experiences of parental neglect are closely related to higher levels of depressive symptoms among adolescents,with social trust serving as a mediating factor.This mediating effect of social trust is particularly significant among females.It is crucial to cultivate a supportive environment and develop a harmonious family atmosphere.