ObjectiveTo establish a new noninvasive， simple， and convenient clinical predictive model by identifying independent predictive factors for rebleeding after endoscopic therapy in cirrhotic patients with esophagogastric variceal bleeding （EGVB）， and to provide a basis for individualized risk assessment and development of clinical intervention strategies. MethodsCirrhotic patients with EGVB who were diagnosed and treated in The First Affiliated Hospital of Xi’an Medical University from September 2018 to October 2023 were enrolled as subjects， and according to whether the patient experienced rebleeding within 1 year after endoscopic therapy， they were divided into rebleeding group with 93 patients and non-rebleeding group with 84 patients. Clinical data were collected and analyzed. The independent samples t-test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. A Logistic model was established based on the results of the univariate and multivariate analyses， and the receiver operating characteristic （ROC） curve and the area under the ROC curve （AUC） were used to assess the accuracy of the model. R software was used to visualize the model by plotting a nomogram， and the Bootstrap method was used for internal validation of the model. ResultsThe multivariate analysis showed that red blood cell count （RBC）， cholinesterase （ChE）， alkaline phosphatase （ALP）， albumin （Alb）， thrombin time （TT）， portal vein trunk diameter， sequential therapy， and primary prevention were independent predictive factors for rebleeding. Based on the results of the multivariate analysis， a logistic model was established as logit（P）=-0.805-1.978×（RBC）+0.001×（ChE）-0.020×（ALP）-0.314×（Alb）+0.567×（TT）+0.428×（portal vein trunk diameter）-2.303×［sequential therapy （yes=1， no=0）］-2.368×［primary prevention （yes=1， no=0）］. The logistic model （AUC=0.928， 95% confidence interval ［CI］： 0.893—0.964， P<0.001） had a better performance in predicting rebleeding than MELD score （AUC=0.603， 95%CI： 0.520—0.687， P=0.003）， Child-Pugh class （AUC=0.650， 95%CI： 0.578—0.722， P=0.001）， and FIB-4 index （AUC=0.587， 95%CI： 0.503—0.671， P=0.045）. The model had an optimal cut-off value of 0.607， a sensitivity of 0.817， and a specificity of 0.817. Internal validation confirmed that the model had good predictive performance and accuracy. ConclusionSequential therapy， implementation of primary prevention， an increase in RBC， and an increase in Alb are protective factors against rebleeding， while prolonged TT and widened main portal vein diameter are risk factors. The logistic model based on these independent predictive factors can predict rebleeding and thus holds promise for clinical application.

OBJECTIVE To investigate the clinical characteristics and risk factors for batroxobin-related severe hypofibrinogenemia （HFIB） and construct a risk prediction model. METHODS A retrospective analysis was conducted on inpatients treated with batroxobin in the First Medical Center of a tertiary hospital from January 1， 2020， to December 31， 2024. Patients were categorized into non-severe HFIB group and severe HFIB group based on the severity of HFIB. Univariate and multivariate Logistic regression analyses were performed to identify the independent influencing factors for batroxobin-related severe HFIB. A nomogram was developed using the “rms” package in R 4.5 software. The predictive performance of the model was evaluated using the receiver operating characteristic curve. Calibration was assessed via the Bootstrap resampling method， and goodness-of-fit was evaluated with the Hosmer-Lemeshow test. RESULTS A total of 1 472 patients were included in this study. Of these， 1 445 developed HFIB， yi elding an incidence of 98.17%. Furthermore， 895 were classified as severe HFIB， accounting for 60.80% of the cohort. Multivariate Logistic regression analysis showed that increased age， high initial dose per 10 kg body weight， use of maintenance dose， and concomitant glucocorticoid use were independent risk factors for batroxobin-related severe HFIB， while high baseline fibrinogen （FIB） level was identified as a protective factor. The model demonstrated an area under the curve of 0.760 （95% CI： 0.735-0.785）. The mean absolute error of the calibration curve was 0.006. The P value of the Hosmer-Lemeshow test was 0.609. CONCLUSIONS Batroxobin can rapidly and significantly reduce FIB levels and carries a risk of inducing severe HFIB. Patients with advanced age， high initial dose per 10 kg body weight， use of maintenance dose and concomitant glucocorticoid use had a higher risk of batroxobin-related severe HFIB， while high baseline FIB level had a lower risk of batroxobin-related severe HFIB. The risk prediction model developed based on these factors can be used to predict the likelihood of batroxobin-related severe HFIB.

ObjectiveTo explore the mechanism through which Banxia Baizhu Tianmatang ameliorates cognitive impairment in epileptic rats induced by lithium chloride-pilocarpine by regulating the neuroinflammatory reaction mediated by NOD-like receptor protein 3 （NLRP3） inflammasomes. MethodsSixty male SD rats were randomly allocated into blank， model， carbamazepine （0.125 g·kg^-1·d^-1）， Banxia Baizhu Tianmatang （1.04 g·kg^-1·d^-1）， and carbamazepine （0.125 g·kg^-1·d^-1） + Banxia Baizhu Tianmatang （1.04 g·kg^-1·d^-1） groups （n=12）. After the modeling of epilepsy， rats were administrated with corresponding agents by gavage for 12 weeks. At the 6th and 12th week of the intervention， the rats’ hyper-excited behavior was evaluated by the stylus experiment， and at the 12^th week of intervention， the cognitive function was evaluated by Barnes maze. At the same time， the seizure frequency and severity grade （Racine score） were recorded. The serum and hippocampus tissue samples were collected after anesthesia for the following tests. Nissl staining was used to evaluate the degree of neuronal damage in the hippocampal CA1 area. The content of malondialdehyde （MDA） in the hippocampus was determined by the thiobarbituric acid （TBA） method. Serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18） were quantified by enzyme-linked immunosorbent assay （ELISA）. Immunohistochemical method was adopted to detect the expression of apoptosis-associated speck-like protein containing a card （ASC） in the hippocampus. Western blot was employed to quantitatively analyze the protein levels of NLRP3， cysteinyl aspartate-specific proteinase-1 （Caspase-1）， and brain-derived neurotrophic factor （BDNF） in the hippocampus. ResultsThe model group showed increased stylus scores at the 6th and 12^th week after modeling， a decreased Barnes maze strategy score at the 12^th week， a prolonged incubation period （P<0.05）， elevated serum levels of inflammatory factors （P<0.05）， decreased neurons with scattered arrangement and large gaps in the hippocampus， increased content of MDA in the hippocampus （P<0.05）， an increased positive expression of ASC， and up-regulated protein levels of Caspase-1， NLRP3， and BDNF （P<0.05）. Compared with the model group， the intervention with Banxia Baizhu Tianmatang for 12 weeks was accompanied by a decreased stylus score， epileptic seizures with a decreased score， a decreased number， and shortened duration， an increased Barnes maze strategy score， shortened escape latency （P<0.01）， declined serum levels of inflammatory factors （P<0.05）， regular morphology of hippocampal neurons， reduced MDA content in the hippocampus （P<0.05）， a decreased positive expression of ASC， and down-regulated protein levels of Caspase-1， NLRP3， and BDNF （P<0.05， P<0.01）. In addition， compared with the carbamazepine group， Banxia Baizhu Tianmatang + carbamazepine showed improved performance in controlling the seizure， improved the cognitive behavior score and morphology of hippocampal neurons， alleviated the oxidative stress products， lowered the levels of inflammatory factors， reduced the positive expression of ASC in the hippocampus， and down-regulated the expression of Caspase-1， NLRP3 and BDNF， with no significant differences. ConclusionBanxia Baizhu Tianmatang may reduce neuroinflammation， control epileptic seizures， and ameliorate cognitive impairment by inhibiting the expression of NLRP3 inflammasomes.

ObjectiveAs a common lifestyle habit, alcohol consumption has a controversial association with the onset of Parkinson’s disease (PD). To demonstrate the correlation between alcohol consumption and PD and to identify associated genes, we integrated findings from clinical surveys, genomics, transcriptomics, and animal experiments. MethodsWe investigated the alcohol consumption rates (including both before and after disease onset) among 244 PD patients in China and 177 PD patients from the U.S. NHANES database. Mendelian randomization (MR) analysis was performed using genome-wide association study (GWAS) data for three alcohol-related traits and seven PD-related datasets from the MRC IEU OpenGWAS database. Transcriptomic data from the substantia nigra of PD patients were obtained from three GEO datasets (GSE7621, GSE20141, and GSE49036) to analyze RIT2 gene transcription. Finally, three groups of animal experiments (water/20% ethanol/20% liquor, with 4 C57BL/6J mice per group) were conducted to examine changes in brain RIT2 gene expression and transcriptomic profiles following alcohol consumption. ResultsThe alcohol consumption rates among PD patients in China and the U.S. (9%-18.87%) were significantly lower than the general population rates of 15%-45% in their respective regions (P<0.001), suggesting a possible negative association between alcohol consumption and PD. Subsequently, in 21 bidirectional MR analyses using 3 alcohol-related GWAS datasets and 7 PD-related GWAS datasets, the forward MR analyses (alcohol intake as exposure, PD as outcome) yielded 12 negative associations (OR_IVW<1) and 9 positive associations (OR_IVW>1). Among these, only two negative associations reached statistical significance: alcohol intake frequency (OR_IVW=0.75, 95% CI: 0.60-0.93, P=0.010) and alcohol consumption (OR_IVW=0.20, 95% CI: 0.05-0.83, P=0.026). The forward MR analysis (alcohol intake→PD) identified 235 SNPs, annotated to 316 genes, while the reverse MR analyses (PD→alcohol intake) identified 37 SNPs, annotated to 53 genes. Notably, only the RIT2 gene appeared in both the forward and reverse MR analyses (alcohol intake→PD: rs28597806, rs8083110; PD→alcohol intake: rs4588066). RIT2 is selectively expressed in the human brain (FPKM: 5.259±2.103), with low or no expression in peripheral tissues (FPKM: <1). Analysis of three human substantia nigra transcriptomic datasets revealed a decreasing trend in RIT2 gene expression in PD patients (GSE20141 array signal: 3.49±1.23 vs. 2.33±0.87, P=0.044). Animal experiments demonstrated that administration of 20% ethanol or 20% liquor (approximately 8% ethanol) stimulated a >2-fold upregulation of RIT2 gene expression in the mouse brain. Furthermore, transcriptomic sequencing revealed that the two alcohol-treated groups exhibited 96 (20% ethanol vs. water control) and 4 (20% liquor vs. water control) differentially expressed genes, respectively, indicating that low-dose alcohol consumption can achieve RIT2 upregulation while minimizing impact on other brain genes. In addition to its anti-infective effects, low-dose alcohol consumption primarily influences signaling pathways related to neurodegenerative diseases such as PD and Prion diseases. ConclusionAlcohol consumption is generally considered as a harmful lifestyle habit. However, some studies have also shown a lower risk of mortality among individuals who consume low doses of alcohol (100 g/week of ethanol) or drink occasionally. Currently, one of the research focuses on alcohol consumption is whether the human body can benefit from low-dose alcohol intake. This study provides new evidence supporting a negative association between alcohol consumption and PD, and for the first time, through MR analysis, identifies the RIT2 gene as a potential mediator of the effect of alcohol consumption on PD. RIT2 is selectively expressed in the human brain. Building upon existing evidence indicating downregulated RIT2 gene expression in PD pathogenesis, our experiments confirm that low-dose alcohol consumption can upregulate RIT2 expression in the brain. In brief, alcohol consumption may suppress the pathogenesis of PD by upregulating RIT2 expression in the substantia nigra. China is facing a serious problem of population aging. This study offers important insights for long-term PD prevention and treatment strategies, with the aim of benefiting more potential PD patients through lifestyle modifications, thereby improving the quality of life of the aging population and reducing the economic burden on healthcare.

The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis （GS/CACM 337-2023） was released by the China Association of Chinese Medicine on December 13^th， 2023. This expert consensus was developed by experts in methodology， pharmacy， and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine （CACM） and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine （pulmonary diseases） and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung， acute bronchitis， and acute attack of chronic bronchitis from the aspects of applicable populations， efficacy evaluation， usage， dosage， drug combination， and safety. It is expected to guide the rational drug use in medical and health institutions， give full play to the unique value of Qinbaohong Zhike oral liquid， and vigorously promote the inheritance and innovation of Chinese patent medicines.

Objective A non-targeted metabolomics analysis of vitreous fluid from patients with proliferative diabetic retinopathy(PDR)is conducted to explore the"metabolic map"of PDR.This approach aims to deepen the understanding of the disease,identify potential biomarkers.Methods From 35 PDR patients and 30 fresh rhegmatogenous retinal de-tachment(RRD)patients,10 PDR patients with vitreoretinal abnormal adhesions were selected as the experimental group(PDR group),and 10 fresh RRD patients were chosen as the control group(RRD group).Using ultra-high-performance liq-uid chromatography-mass spectrometry non-targeted metabolomics technology,the metabolic profiles of vitreous fluid were analyzed to obtain metabolic spectra.One-dimensional and multidimensional statistical methods were used to analyze the differences in metabolites and metabolic pathways between the PDR and RRD groups.Results A total of 165 differential metabolites were identified in the vitreous humor samples of patients in the PDR and RRD groups,these differential metab-olites were significantly enriched in 21 metabolic pathways(P＜0.05),Among these pathways,those with at least 5 differ-ential metabolites include:methionine and cysteine metabolism;glycine,serine,and threonine metabolism;ascorbic acid and aldose metabolism;amino acid biosynthesis;and central carbon metabolism in cancer.Pyruvate,serine,D-2-phospho-glycerate,threonine,phosphoserine,and high serine are present in multiple metabolic pathways,the areas under the curve are 0.96,0.82,0.85,0.78,0.40,and 0.31,respectively.Conclusion There are 21 significantly different metabolic pathways between PDR and RRD patients.Pyruvate stands out in multiple pathways,potentially serving as a biomarker for PDR diagnosis.

To explore the immunomodulatory effects of a new vegetable oil adjuvant(named E515)containing vitamin E(VE)and ginsenosides(GS)on rabbit peripheral blood lymphocytes and Bordetella of rabbit inactivated vaccine.E515,Bordetella bronchiseptica(Bb)and LPS were co-cultured with rabbit peripheral blood lymphocytes in vitro,and the lymphocyte conversion rate was detected by CCK8 method,and the content of lymphocyte supernatant cytokines was detected by ELISA method.After rabbits were immunized with E515-Bb vaccine,the antibody level was detec-ted by indirect ELISA,the serum cytokine content was detected by ELISA,and the protective effect of E515-Bb vaccine on rabbits was observed by challenge test.In vitro cell experiments showed that E515 could significantly increase lymphocyte proliferation and TH1/TH2 cytokine se-cretion in rabbit peripheral blood.In vivo animal experiments showed that E515 adjuvant could sig-nificantly enhance the level of Bb specific antibody induced by Bordetella vaccine in rabbits.In-crease the secretion level of TH1/TH2 cytokines and decrease the secretion level of TNF-α;It can effectively protect rabbits against Bordetella infection with a protection rate of 91.67％.Therefore,E515 as a new vegetable oil adjuvant deserves further study.

Aim To investigate the effects of circ_0071653 targeting miR-197-3p on the proliferation and metastasis of esophageal squamous cell carcinoma(ES-CC)cells.Methods The circular structure of circ_0071653 was confirmed by Sanger sequencing and ribo-nuclease R tolerance experiments.Real-time quantita-tive polymerase chain reaction(RT-qPCR)and tissue fluorescence in situ hybridization assay were performed to detect the circ_0071653 expression levels and ana-lyze its clinical relevance.Cell fluorescence in situ hy-bridization and nuclear cytoplasmic separation assays were used to verify the subcellular localization of circ_0071653 and miR-197-3p.Bioinformatics analysis,dual luciferase reporter gene and RT-qPCR assays were conducted to validate the interactions between circ_0071653 and miR-197-3p.Moreover,the cell counting Kit-8(CCK-8),colony formation,scratch,Transwell invasion and subcutaneous tumor formation in nude mice assays were used to evaluate the effects of circ_0071653 and miR-197-3p on cell viability,prolifera-tion,migration,and invasion and in vivo tumorigenesi-sability.Results Circ_0071653 was a circular RNA,which showed high expression in ESCC cell lines and tissues.The expression of circ_0071653 was signifi-cantly correlated with lymph node metastasis and clini-cal stage of ESCC patients.Circ_0071653 and miR-197-3p were mainly localized in the cytoplasm.The databases predict that circ_0071653 had complementa-ry binding sites with miR-197-3p,and their binding were confirmed by dual luciferase reporter geneand RT-qPCR assays.Moreover,the activity,proliferation,migration,invasion and in vivo tumorigenesis abilities of ESCC cells were significantly reduced after knocking down circ_0071653,and this effect could be reversed by downregulating the expression of miR-197-3p.Con-clusions Circ_0071653 promotes the malignant pro-gression of ESCC through targeted regulation of miR-197-3p.

Objective To analyze the target,signal pathway and potential mechanism of Banxia Baizhu Tianma Decoction in the treatment of epilepsy based on network pharmacology,and to verify it by molecular docking technology and animal experiments.Methods The active ingredients and drug targets of Banxia Baizhu Tianma Decoction were screened by BATMAN and other databases.The targets of epilepsy-related diseases were obtained by GeneCards and other databases,and the intersection targets were taken.Constructing'drug-ingredient-target-disease'network and PPI network to screen the core targets.The core active ingredients were screened according to GO,KEGG functional enrichment analysis and'pathway-target-active ingredient'network.Molecular docking was used to verify the core targets and core active ingredients.In the animal experiment,the rat model of epilepsy was induced by lithium chloride-pilocarpine,and 40 Wistar rats were divided into normal control group,model control group,carbamazepine group and Banxia Baizhu Tianma Decoction group.The seizures were observed by behavior.Nissl staining was used to observe neuronal damage in hippocampus.Immunohistochemistry was used to detect the expression of BAX,BCL-2 and Caspase-3 protein.Results A total of 1072 targets of Banxia Baizhu Tianma Decoction were screened,1046 disease targets of epilepsy were screened,and 220 intersection targets of Banxia Baizhu Tianma Decoction in the treatment of epilepsy were screened.The core targets AKT1,ALB,ACTB,INS and TNF of PPI network were obtained.KEGG pathway mainly involves TNF signaling pathway,IL-17 signaling pathway,cAMP signaling pathway,pathways of neurodegeneration-multiple diseases,serotonergic synapse and Dopaminergic synapse.The core active ingredients with the highest correlation in the'pathway-target-active component'network were Betulin,Ephedrine,Ergotamine and Thymol.Results of molecular docking indicated that the core target had satisfactory affinity with those active ingredients.Animal experiments showed that Banxia Baizhu Tianma Decoction could effectively reduce epileptic seizures in rats,improve hippocampal neuronal damage in rats,significantly reduce the percentage of neuronal apoptosis,significantly down-regulate the expression of pro-apoptotic proteins BAX and Caspase-3,and up-regulate the expression of anti-apoptotic protein BCL-2.Conclusion Banxia Baizhu Tianma Decoction has the characteristics of multi-component,multi-target and multi-pathway in the treatment of epilepsy.Inhibiting neuronal apoptosis and reducing hippocampal neuronal damage may be one of the important mechanisms for its treatment of epilepsy.

Persistent atrial fibrillation and other factors can cause mitral and tricuspid annular dilation and leaflet regurgitation,leading to severe functional mitral and tricuspid regurgitation.Patients often experience significant heart failure symptoms and poor prognosis.For patients with severe mitral or tricuspid regurgitation who are at high risk or contraindicated for surgical procedures,transbronchial repair(TEER)is an important alternative therapy that can effectively reduce valve regurgitation and improve cardiac function;Although there is a lack of large-scale data on atrial functional reflux,existing experience still shows that TEER can significantly reduce reflux and improve patients'quality of life.However,double valve intervention therapy poses challenges,especially when combined with TEER repair,which is technically more complex,time-consuming,and carries higher risks.Foreign data shows that simultaneous or staged double valve intervention can safely improve cardiac function and increase survival rates,but the optimal intervention strategy still needs further research.Due to the fact that tricuspid TEER devices have not yet been launched in China,only staged treatment can be adopted at present.This case report shows a patient with severe atrial functional mitral and tricuspid regurgitation who underwent staged transcatheter edge to edge repair surgery successfully.During a 1-year follow-up,bilateral valve regurgitation continued to improve,indicating that staged repair of bilateral atrioventricular valve regurgitation through the catheter margin is a feasible and effective treatment option.