Acute myocardial infarction(AMI)is a common cardiovascular emergency in clinic.Early reperfusion is a typical and effective method for the treatment of AMI.However,the recovery of blood supply after reperfusion therapy will accelerate the damage of ischemic myocardium and cause myocardial ischemia-reperfusion injury(MI/RI).In recent years,studies have found that TCM has the unique advantages of multi-component,multi-channel and multi-target in the intervention of MI/RI.Janus tyrosine kinase/signal transducer and activator of transcription(JAK/STAT)signaling pathway is closely related to MI/RI,which can reduce MI/RI process by regulating inflammation,oxidative stress,cell proliferation,differentiation and apoptosis.This article reviewed the mechanism of JAK/STAT signaling pathway in MI/RI and the research of TCM targeting this pathway,in order to provide references for the prevention and treatment of MI/RI and further drug development.

Objective:Hepatic fibrosis is a common pathological basis for many chronic liver diseases and can progress to cirrhosis,a leading cause of mortality in liver diseases.Early identification and reversal of hepatic fibrosis are key in the treatment of chronic liver disease.This study aims to compare the expression levels of serum core fucosylated low molecular weight kininogen(LMWK-Fc)and alpha-galactosylated(α-Gal)antibodies in patients with hepatic fibrosis at different stages,and to evaluate their diagnostic efficacy for hepatic fibrosis. Methods:A retrospective analysis was conducted on 275 patients with chronic liver disease who visited the Department of Infectious Diseases at the Second Xiangya Hospital of Central South University between June 2022 and March 2023.Among these,115 patients underwent liver biopsy.Based on the extent of collagen deposition and its impact on liver structure and microcirculation,patients were staged from 0 to 4:S0(no significant collagen deposition in liver tissues;liver structure and microcirculation are normal),S1(mild collagen deposition in liver tissues,with partial disruption of lobule structure,but microcirculation remains largely normal),S2(moderate collagen deposition in liver tissues,with partial disruption of lobule structure and microcirculation),S3(extensive collagen deposition in liver tissues,with substantial disruption of lobule structure and microcirculation),and S4(development of cirrhosis,with heavy collagen deposition,complete disruption of lobule structure,and severe impairment of microcirculation).Patients were grouped as no fibrosis(S0),fibrosis(S1-S2),and significant fibrosis(S3-S4).For the 160 patients without liver biopsy,they were categorized based on liver stiffness measurement(LSM)value:no fibrosis(F0:LSM＜7.3 kPa),fibrosis(F1-F2:LSM 7.3-12.4 kPa),and significant fibrosis(F3-F4:LSM＞12.4 kPa).Demographic data(age,gender)and laboratory indicators(alanine transaminase,aspartate transaminase,gamma-glutamyl transferase,alkaline phosphatase,alpha-fetoprotein,platelet count)were collected to calculate the fibrosis-4 index(FIB-4)and aspartate aminotransferase-to-platelet ratio index(APRI).Serum LMWK-Fc and α-Gal antibodies were measured and compared across the groups,and their correlation with fibrosis severity was analyzed.The receiver operating characteristic(ROC)curve was used to assess the predictive value of serum LMWK-Fc and α-Gal antibody levels for hepatic fibrosis. Results:Among the 160 patients without complete liver biopsy,serum α-Gal antibody and LMWK-Fc levels increased progressively from the no fibrosis group to the significant fibrosis group,with statistically significant differences(P＜0.05).Among the 115 patients with liver biopsy,serum LMWK-Fc levels were significantly higher in the fibrosis group and the significant fibrosis groups compared with the no fibrosis group,and α-Gal antibody levels were significantly higher in the significant fibrosis group compared with the no fibrosis group and the fibrosis group(P＜0.001,P=0.032,respectively).Univariate and multivariate linear regression analyses showed that hepatic fibrosis was correlated with gender and LMWK-Fc levels(both P＜0.05),but not with age,α-Gal antibody levels,FIB-4,or APRI(all P＞0.05). Conclusion:The expression levels of serum LMWK-Fc and α-Gal antibodies vary across different stages of hepatic fibrosis,suggesting a potential association with fibrosis progression.LMWK-Fc levels have a certain predictive value for the diagnosis of hepatic fibrosis.

AIM:To explore the potential targets and mechanisms of Angelica sinensis and Astraga-lus membranaceus ultrafiltration(RAS-AM)in the treatment of radiation induced myocardial fibrosis(RIMF)through network pharmacology combined experimental validation.METHODS:Using the TC-MSP database TCM@TAIWAN The Taiwan Tradition-al Chinese Medicine Database and TCMID Tradition-al Chinese Medicine Database screen the compo-nents and targets of RAS-AM,and use the Swiss Target Prediction database for target prediction.Obtain RIMF disease targets from Gene Cards and OMIM databases,obtain intersection targets of dis-eases and drugs through Wayne's online tool,ob-tain protein interaction relationships(PPIs)through STRING database,and use Cytoscape 3.9.1 soft-ware to construct a visualized network topology di-agram of"drug component target disease".Con-duct GO and KEGG enrichment analysis on core tar-gets through the David database,and use the mi-crobiome platform for mapping.Experimental veri-fication:Sixty Wistar rats were randomly divided in-to a blank group,a model group,a positive drug group,a RAS-AM low-dose group,a RAS-AM medi-um dose group,and a RAS-AM high-dose group.A RIMF model was established using a 38Gy dose of radiation induction,and was administered orally for 4 weeks.The general condition of the rats was also observed.After blood and heart collection in rats,HE staining was used to observe the morpho-logical changes of myocardial tissue,and ELISA and Western blot methods were used to detect key tar-gets for network pharmacology prediction.RE-SULTS:Network pharmacology analysis revealed 34 active components and 705 targets of Angelica si-nensis and Astragalus membranaceus ultrafiltra-tion,with a total of 154 targets,with IL-6,VEGFA,MMP2,MMP9,and ACE as the top five core tar-gets;GO enrichment analysis screened a total of 153 entries,and KEGG enrichment had 25 path-ways.Experimental part:HE staining results showed that the degeneration and necrosis of myo-cardial cells improved in each medication group,the infiltration of inflammatory cells in the myocar-dial interstitium decreased,and the proliferation of fibrous connective tissue in the myocardial intersti-tium decreased.ELISA and Western blot results showed that compared with the normal group,the expression of IL-6,VEGFA,and MMP-9 in the mod-el group increased.Compared with the model groupthe expression of IL-6,VEGFA,and MMP-9 in each medication group decreased to varying de-grees,in a dose-dependent manner.CONCLUSION:RAS-AM may inhibit RIMF by downregulating core targets such as IL-6,VEGFA protein,MMP-9 pro-tein,and regulating inflammatory pathways,colla-gen degradation,and other processes.

Objective To observe the effects of Angelica Sinensis Radix and Astragali Radix extract(ASR-AR)on HUVEC pyroptosis;To explore its mechanism of treating coronary microvascular disease.Methods HUVEC were divided into blank group,model group,MCC950 group,ASR-AR low-,medium-and high-dosage groups.After modeling and treatment with drug containing serum,cell viability was detected by CCK-8 method,and cell apoptosis was detected by flow cytometry,phalloidin staining was used to detect cytoskeletal morphology,immunofluorescence staining was used to detect the expressions of VEGF,eNOS,Ang-2,ROS,ET-1 and TXA2,ELISA was used to detect the contents of IL-1β and IL-18 in cell supernatant,Western blot was used to detect the expressions of NLRP3,ASC,Caspase-1 and GSDMD protein in cells.Results Compared with the blank group,the model group showed a decrease in HUVEC cell viability(P<0.01)and an increase in cell apoptosis rate(P<0.01),cellular microfilament structure was in disorder and knotting,the expressions of VEGF and eNOS decreased,and expressions of Ang-2,ROS,ET-1 and TXA2 increased,the contents of IL-1β and IL-18 in cell supernatant increased(P<0.01),and the expressions of NLRP3,ASC,Caspase-1 and GSDMD protein in cells increased(P<0.01).Compared with the model group,ASR-AR low-,medium-and high-dosage containing serum could increase cell viability(P<0.05),decrease cell apoptosis rate(P<0.05),improve cell microfilament structure,elevate VEGF and eNOS expressions,decrease Ang-2,ROS,ET-1,TXA2 expressions,reduce IL-1β and IL-18 contents in cell supernatant(P<0.05),and decrease NLRP3,ASC,Caspase-1 and GSDMD protein expressions(P<0.05).ASR-AR medium-dosage group was more obvious(P<0.05).Conclusion ASR-AR can inhibit pyroptosis of HUVEC induced by AngⅡ,attenuate endothelial cell dysfunction,thus treating coronary microvascular disease,and its mechanism may be related to the inhibition of the assembly of NLRP3 inflammasome.

Myocardial infarction （MI） is a common cardiovascular disease in clinical practice and one of the main causes of cardiovascular mortality. Its pathogenesis is complex and associated with oxidative stress reactions. Nuclear factor E₂-related factor 2 （Nrf2） is a key factor in regulating oxidative stress reactions. It can regulate the expression of heme oxygenase-1 （HO-1）， playing a role in maintaining the oxidative-reductive homeostasis in the body. During the course of MI， the biological activity and levels of Nrf2 and HO-1 decrease， leading to weakened tissue antioxidant and anti-inflammatory capabilities， endothelial damage in myocardial blood vessels， release of vascular cell adhesion factors， and impaired endothelial function. In recent years， many basic research studies have explored the role and mechanisms of traditional Chinese medicine （TCM） in treating MI by modulating the Nrf2/HO-1 signaling pathway. The results have indicated that the Nrf2/HO-1 signaling pathway is an important potential target for TCM in the treatment of MI. This article reviewed the mechanism of the Nrf2/HO-1 signaling pathway in MI and the research progress of TCM in targeting and regulating this pathway， aiming to provide a theoretical basis for the prevention and treatment of MI and further drug development.

Background/Aims: This study aimed to investigate the biological function and regulatory mechanism of TCN1 in colorectal cancer (CRC). Methods: We studied the biological function of TCN1 by performing gain-of-function and loss-offunction analyses in HCT116 cell lines; examined the effects of TCN1 on the proliferation, apoptosis, and invasion of CRC cells; and determined potential molecular mechanisms using HCT116 and SW480 CRC lines and mouse xenotransplantation models. Tumor xenograft and colonization assays were performed to detect the tumorigenicity and metastatic foci of cells in vivo. Results: TCN1 knockdown attenuated CRC cell proliferation and invasion and promoted cell apoptosis. Overexpression of TCN1 yielded the opposite effects. In addition, TCN1-knockdown HCT116 cells failed to form metastatic foci in the peritoneum after intravenous injection. Molecular mechanism analyses showed that TCN1 interacted with integrin subunit β4 (ITGB4) to positively regulate the expression of ITGB4. TCN1 knockdown promoted the degradation of ITGB4 and increased the instability of ITGB4 and filamin A. Downregulation of ITGB4 at the protein level resulted in the disassociation of the ITGB4/plectin complex, leading to cytoskeletal damage. Conclusions TCN1 might play an oncogenic role in CRC by regulating the ITGB4 signaling pathway.

Objective:To explore the impact of donor cold ischemia time(CIT)on early recovery after liver transplantation(LT).Methods:From January 2016 to December 2020, the relevant clinical data were retrospectively reviewed for 456 LT recipients.According to the value of CIT of donor liver, they were assigned into two groups of CIT >5 h and CIT≤5 h. T, Mann-Whitney U or Chi square test was employed for statistical processing.Intraoperative findings and liver function(LF)parameters of two groups were compared, including operative duration, intraoperative volume of hemorrhage, erythrocyte transfusion and anhepatic phase.LF parameters included alanine aminotransferase(ALT), aspartate aminotransferase(AST)and total bilirubin(TB)within Day 1-7 post-LT.Postoperative recovery was evaluated by postoperative stay of intensive care unit(ICU), normalization time of liver function recovery, length of postoperative hospitalization and incidence of postoperative complications.Results:Among them, 407(89.3%)patients underwent classic orthotopic LT.Median CIT of donor liver was 309 min.In CIT≤5 h and CIT >5 h groups, operative duration was[(446.3+ 76.8)vs.(526.0+ 98.1)min], anhepatic phase time[(51.9+ 13.3)vs.(62.6+ 18.9)min]and intraoperative volume of erythrocyte transfusion[(7.3+ 5.8)vs.(10.0+ 6.87)U]. And the differences were statistically significant( P<0.001, 0.001 & 0.001). Postoperative hospitalization stay was longer[(29.1±15.9)vs.(27.1±13.0)]day.And the incidence of postoperative complications was higher in CIT >5 h group[22.7%(54/238)vs.12.4%(27/218)]. And the difference was statistically significant( P=0.045 & 0.004). As compared with CIT≤5 h group, ALT, AST & TB spiked in CIT >5 h group at Day 1 post-operation and the differences were statistically significant( P=0.002, P<0.001, P=0.001). In CIT >5 h group, ALT rose at Day 2/5/6/7 post-LT( P=0.026, 0.026, 0.015 & 0.011), AST jumped from Days 2-6( P=0.002, 0.004, 0.035, 0.029 and 0.019)and TB increased from Days 2-7 post-LT and the differences were statistically significant( P=0.003, 0.014, 0.030, 0.039, 0.027 & 0.009). LF recovered at CIT≤5 h and CIT>5 h group[(10.0±3.2)vs.(10.7±3.3)day]. There were significantly statistical differences( P=0.044). Conclusions:Non-conducive to patient recovery, prolonged cold ischemic time aggravates early LF injury post-LT.

Objective To clarify the intervention effect of Angelica Radix Astragali ultrafiltrate(RAS-RH)on radiation-induced myocardial fibrosis by inhibiting the overexpression of cardiac CILP1.Methods Forty SPF Wistar male rats were randomly divided into normal group,model group,Benazepril hydrochloride group,RAS-RH group and Benazepril hydrochloride +RAS-RH group.Cardiomyocytes were induced by X-ray.The rat model of myocardial fibrosis was prepared by injury.The benazepril hydrochloride group was given benazepril hydrochloride 1.0 mg·kg-1 by gavage;the RAS-RH group was given RAS-RH 0.6 g·kg-1 by gavage;benazepril hydrochloride was given by gavage Pril + RAS-RH group was given benazepril hydrochloride 1.0 mg·kg-1 and RAS-RH 0.6 g·kg-1 by gavage;model group and normal group were given equal volume of normal saline by gavage,once a day,After 4 weeks of drug intervention,the serum NT-ProBNP,CTnⅠ and CTnT contents of the rats in each group were detected by ELISA method;HE staining was used to evaluate the pathological changes of myocardial tissue of the rats in each group;Masson staining was used to evaluate the myocardial collagen deposition of the rats in each group and calculated Collagen volume fraction(CVF);immunohistochemistry to detect the expression levels of α-SMA,Col-Ⅰ,Col-Ⅲ protein in myocardial tissue of rats in each group;Western blot method to detect TGF-β1 and smad3 in myocardial tissue of rats in each group,CILP1 protein expression.Results Compared with the blank group,the serum levels of NT-ProBNP,CTnⅠ and CTnT in the model group were significantly increased(P<0.01).Blue-stained fibrous tissue increased significantly,myocardial CVF increased significantly,and myocardial tissue α-SMA,Col-Ⅰ,Col-Ⅲ,TGF-β1,Smad3,CILP1 protein expression increased(P<0.01);Serum contents of NT-ProBNP,cTnⅠ and CTnT in rats in napril group,RAS-RH group and benazepril hydrochloride + RAS-RH group were significantly decreased(P<0.01).Sexual cell infiltration was improved,myocardial CVF was significantly decreased(P<0.01),and the protein expressions of α-SMA,Col-Ⅰ,Col-Ⅲ,TGF-β 1,Smad3 and CILP1 in myocardial tissue were significantly decreased(P<0.05).Conclusion Angelica sinensis ultrafiltrate can alleviate X-ray radiation-induced myocardial fibrosis in rats by inhibiting the overexpression of CILP 1 in the heart.

AIM: To study the mechanism of Ginseng Yixin granules (QSYXG) in treating ejection fraction preserved heart failure (HFpEF) based on network pharmacology. METHODS: Effective chemical composition information of QSYXG particles was collected through TCMSP database; DisGeNET, GeneCards, OMIM database for obtaining HFpEF related targets; Metascape GO and KEGG enrichment analysis of the intersection targets of HFpEF; STRING Construction and analysis of the database PPI network; Cytoscape3.7.2 Software construction network diagram; Docking of the major active components to the core target with the AutoDock Vina software molecules, the results were visualized and analyzed with pymol. RESULTS: A total of 66 components and corresponding targets were obtained, HFpEF corresponds to 1 931 targets, The intersection of 127 targets, the main active ingredients are quercetin, kaempferol, β-sitosterol, etc.; TNF, AKT1, IL-6, P53 and JUN as the core targets, Good docking of the key components with the core targets; Mainly involving the positive regulation of gene expression, signal transduction, negative regulation of apoptotic process, positive regulation of cell proliferation and senescence, hypoxia response, negative regulation of gene expression, inflammatory response and so on, PI3K-Akt, AGE-RAG, MAPK, TNF, IL-17, and HIF-1 are the main associated signaling pathways. CONCLUSION: QSYXG may treat HFpEF by activating targets of TNF, AKT1, IL-6, P53, JUN, and regulating apoptotic process, cell proliferation, hypoxia response, and inflammatory response.

Background/Aims: Colorectal cancer (CRC) patients often exhibit peritoneal metastasis, which negatively impacts their prognosis. CD31 and D2-40 have recently been suggested to be predictors of breast cancer prognosis, but their role in colorectal peritoneal metastasis (CRPM) remains unknown. Methods: The expression profiles of CD31 and D2-40 were analyzed in CRC patients with or without CRPM and in CRC cell lines with increasing metastatic potential. Overexpression and short hairpin RNA knockdown assays were performed in CRC cells, and the effects of these alterations on epithelial-mesenchymal transition (EMT) in vitro, growth of xenograft tumors in vivo, and peritoneal metastasis potential in a mouse model of CRPM were examined. Results: The expressions of CD31 and D2-40 were upregulated in CRC tumor tissues and was elevated further in tumor tissues from patients with CRPM. CD31 and D2-40 expression levels exhibited increasing trends parallel to the EMT potential of CRC cells. CD31 and D2-40 are essential for CRC cell EMT in vitro as well as for xenograft tumor growth and peritoneal metastasis in vivo. Conclusions CD31 and D2-40 contribute to CRPM by promoting EMT and may serve as prognostic markers and therapeutic targets for CRC, particularly in patients with peritoneal metastasis.