Objective To investigate the effects of icariin on myocardial cell apoptosis and transforming growth factor-β1(TGF-β1)/Smad3 signaling pathway in rats with septic myocardial damage.Methods A septic myocardial damage model was established in SD rats via intraperitoneal injection of lipopolysaccharide.The rats with septic myocardial damage were randomly divided into model,low-dose icariin,high-dose icariin,and high-dose icariin+SRI-011381 groups(n=10 per group).An additional 10 rats that received intraperi-toneal injection of an equal volume of normal saline served as the control group.The left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular ejection fraction(LVEF),and left ventricular systolic pressure(LVSP)were detected using ultrasound instrument.Hematoxylin and eosin(HE)staining was used to detect the morphology of myocardial tissue.Trans-mission electron microscopy was used to measure the ultrastructure of myocardial tissue.The enzyme-linked immunosorbent assay was used to detect the serum markers of myocardial damage including cardiac troponin T(cTnT)and creatine kinase isoenzyme-MB(CK-MB)and inflammatory cytokines including interlenkin-6(IL-6)and tumor necrosis factor α(TNF-α).Western blotting was performed to assess the expression of TGF-β1/Smad3 pathway-related proteins in the myocardial tissue of rats in each group.Results Compared with the control group,LVEDD,LVESD,myocardial pathological score,myocardial cell apoptosis rate,the cTnT,CK-MB,IL-6,and TNF-α levels,TGF-β1 protein expression,and p-Smad3/Smad3 in the model group were higher(P＜0.05),while LVEF and LVSP were lower(P＜0.05).Compared with the model group,the pathological indictors of rats in the low-and high-dose icariin groups were improved,and high-dose icariin had a stronger effect.SRI-011381 could weaken the improvement effect of icariin on various pathological indicators in rats with septic myocardial damage.Conclusion Icariin can inhibit the inflammatory response in rats with sepsis by blocking the activation of the TGF-β1/Smad3 signaling pathway,thereby reducing myocardial cell apoptosis and myocardial damage.

Objective To investigate whether evodiamine(EVO)can alleviate liver injury in septic rats by influencing the nucleo-tide-binding and oligomerization domain(NOD)-like receptor protein 3(NLRP3)/interleukin-1 β(IL-1β)/caspase-1 signaling pathway.Methods A rat model of sepsis-induced liver damage was constructed,and the successfully modeled rats were assigned to the model,L-EVO,M-EVO,H-EVO(administered orally at 4,8,and 16 mg/kg of EVO),and H-EVO+NLRP3(administered orally at 16 mg/kg of EVO+intraperitoneal injection of 1 mg/kg of NLRP3 signaling pathway activator sodium salt)groups,each with ten rats.In addition,ten normal rats were selected as the control group(that is,the sham surgery group,without ligation or puncture,using the same steps as for the model group).The control and model groups were administered with equal amounts of physiological saline once daily for 28 d,consecutively.A reagent kit was used to assess rat liver function.Hematoxylin and eosin(HE)staining was used to analyze pathological changes in the liver tissue.Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)staining was used to assess apoptosis in liver tissue cells.ELISA was used to analyze IL-6,tumor necrosis factor α(TNF-α),and IL-1β levels in serum.Western blotting was used to detect changes in protein expression of the NLRP3/IL-1β/caspase-1 signaling pathway components in liver tissues.Results For the control group,the liver tissues of rats in the model group lost their normal structure,with an uneven distribution of liver cells accompanied by edema and vacuoles.For the model group,the L-EVO,M-EVO,and H-EVO groups exhibited a relatively neat arrangement of liver tissue cells,reduced edema,and vacuoles.As the dose increased,the morphology of liver tissue cells recovered significantly.For the H-EVO group,the H-EVO+NLRP3 group exhibited a disordered arrangement of liver tissue cells with edema and vacuoles.For the control group,the model group showed increased alanine aminotransferase(ALT),aspartate aminotransferase(AST),liver tissue cell apoptosis rate,serum IL-6,TNF-α,and IL-1β levels,and expression of NLRP,IL-1β,and caspase-1 protein in the liver tissue(P＜0.05).For the model group,the L-EVO,M-EVO,and H-EVO groups showed lower ALT,AST,liver tissue cell apoptosis rate,serum IL-6,TNF-α,and IL-1β levels,and expression of NLRP,IL-1β,and caspase-1 protein in the liver tissue(P＜0.05).For the H-EVO group,the H-EVO+NLRP3 group had higher ALT,AST,liver tissue cell apoptosis rate,serum IL-6,TNF-α,and IL-1β levels,and expression of NLRP,IL-1β,and caspase-1 pro-tein in the liver tissue(P＜0.05).Conclusion EVO can alleviate liver injury in septic rats by influencing the NLRP3/IL-1β/caspase-1 signaling pathway.

Objective To investigate the value of afterload-related cardiac performance(ACP)in evaluating cardiac dysfunction and prognosis in patients with septic shock.Methods This prospective observational study included 45 patients with septic shock.The patients were divided into the death(n=21)or survival(n=24)group according to whether they died within 28 days.Baseline and labora-tory data were collected within 24 h.Cardiac function indices were collected and monitored at 0,6,12,18,and 24 h using the pulse index continuous cardiac output.Variables affecting the prognosis were included in the multivariate Cox proportional hazard model.Prognosis was predicted using a receiver operating characteristic(ROC)curve.Results The ACP in the death group was significantly lower than that in the survival group at 0,6,12,18,and 24 h(all P＜0.05).Logistic regression analysis showed that decreased ACP,increased acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score,increased sequential organ failure assessment(SOFA)score,increased fluid balance at 24 h,increased vasoactive-inotropic score,increased central venous pressure,and decreased mean arterial pressure were risk factors for poor prognosis.The Cox proportional hazard model showed that ACP,APACHE Ⅱ score,and SOFA score were independent risk factors influencing prognosis.ROC analysis showed that the area under the curve of ACP was the largest at 24 h,which was the best time point for predicting 28-day mortality.The corresponding sensitivity,specificity,and best cutoff values were 76.20％,91.70％,and 75.16％,respectively.Conclusion ACP could be used as a valuable index to evaluate cardiac dysfunction and as an independent risk factor for poor prognosis in patients with septic shock.

Objective To investigate the roles of glucose-regulated protein 75(GRP75)and voltage-dependent anion channel 1(VDAC1)in heroin-induced arrhythmia.Methods Based on transcriptomic data from primary myocardial cells treated with heroin and the GSE31821 dataset from the Gene Expression Omnibus(GEO),differentially expressed genes(DEGs)were identified using R software.Enrichment analysis of DEGs was performed.The protein-protein interaction(PPI)network was constructed using STRING database,and key genes were selected using Cytoscape.Molecular docking of key genes was performed using HDOCK,followed by in vivo valida-tion.A total of 60 SD rats were randomly divided into control,model,model+7 d,model+14 d,and model+21 d groups.A rat model of heroin addiction was established,and the expression levels of DEGs in myocardial tissue were assessed using immunohistochemical staining and quantitative real-time PCR.Results A total of 51 DEGs primarily enriched in muscle cell development,myofibrils,actin binding,arrhythmic right ventricular cardiomyopathy,calcium signaling,and apoptosis pathways were identified.Based on the PPI and Cytoscape analyses,GRP75 and VDAC1 were identified as key genes.Molecular docking indicated a strong interaction between GRP75 and VDAC1,which form a stable complex.The results of immunohistochemical staining and qRT-PCR showed that the expression levels of GRP75 and VDAC1 were significantly increased in the model group compared to those in the control group(P＜0.05),and their expres-sion increased(P＜0.05)with the intervention period of heroin in a time-dependent manner.Conclusion GRP75 and VDAC1 may con-tribute to heroin-induced arrhythmogenesis.

Objective To investigate the effect of isoorientin(ISO)on lipopolysaccharide(LPS)-induced myocardial cell damage through regulation of the high-mobility group protein B1(HMGB1)receptor for the advanced glycation end-product(RAGE)signaling pathway.Methods H9c2 myocardial cells were incubated with LPS,and the cells were randomly assigned to an LPS induction group(Model group,1 μg/mL LPS),a low concentration ISO intervention group(ISO-L group,50 μmol/L ISO),a high concentration ISO interven-tion group(ISO-H group,100 μmol/L ISO),or a high concentration ISO+RAGE activator late glycation end-products(AGES)group(ISO-H+AGES group,100 μmol/L ISO+10 μg/mL AGES),with an additional control group(Control group).A cell counting kit 8 assay was used to determine the viability of the H9c2 cells.Flow cytometry was used to determine the rate of apoptosis of the H9c2 cells.An ELISA kit was used to determine the levels of oxidative stress-related factors,superoxide dismutase(SOD),malondialdehyde(MDA),and glutathione peroxidase(GSH-Px)in the H9c2 cells.ELISA method was also used to determine the levels of inflammatory factors,interleukin-1β(IL-1 β),tumor necrosis factor α(TNF-α),and lactate dehydrogenase(LDH)in the H9c2 cells.Western blotting was used to determine the expression levels of the HMGB1-RAGE signaling pathway and apoptosis-related proteins in the H9c2 cells.Results Compared with the Control group,the expression levels of optical density(OD)at 450 nm(48 h and 72 h),SOD,GSH-Px,and B-cell lymphoma-2(Bcl-2)proteins in the H9c2 cells in the Model group were significantly reduced(P＜0.05),and the apoptosis rate,MDA,IL-1β,TNF-α,and LDH levels,and the expression levels of HMGB1,RAGE,Bcl-2 associated X protein(Bax),and cleaved caspase-3 proteins were significantly increased(P＜0.05).Compared with the Model group,the expression levels of OD450(48 h and 72 h),SOD,GSH-Px,and Bcl-2 proteins in the H9c2 cells in the ISO-L and ISO-H groups were significantly increased(P＜0.05),and the apoptosis rate,MDA,IL-1β,TNF-α,and LDH levels,and the expression levels of HMGB1,RAGE,Bax,and cleaved caspase-3 proteins were significantly decreased(P＜0.05).AGES weakened the alleviating effect of ISO on LPS-induced H9c2 cell damage.Conclusion ISO alleviates LPS-induced myocardial cell damage by inhibiting excessive activation of the HMGB-RAGE signaling pathway.

Objective To analyze the expression of long non-coding RNA(lncRNA)ABHD11-AS1 in clear cell renal cell carcinoma(ccRCC)and renal cancer cell lines,and explore its potential functions and mechanisms of action.Methods The bioinformatics tool GEPIA2 software was used to analyze The Cancer Genome Atlas(TCGA)database and compare the expression levels of ABHD11-AS1 in ccRCC and normal kidney tissues.Real-time quantitative PCR was performed to assess ABHD11-AS1 expression in ccRCC tissues,normal kidney tissues,and renal cancer cell lines.Subcellular localization experiments were performed to determine the subcellular locali-zation of ABHD11-AS1 in renal cancer cells.The MTT assay,Transwell assay,real-time quantitative PCR,and Western blotting were used to detect the effects of ABHD11-AS1 and miR-133a-3p on the proliferation,invasion,and expression of SLC6A1 in renal cancer cells.A dual-luciferase reporter gene experiments was performed to validate the binding effect of ABHD11-AS1 to miR-133a-3p and the effect of miR-133a-3p on SLC6A1.Results GEPIA2 software and real-time quantitative PCR analyses indicated that ABHD11-AS1 was highly expressed in ccRCC tissues compared to normal kidney tissues(P＜0.05).Compared to the immortalized renal tubular epithelial cell line HK-2 cells,the expression of ABHD11-AS1 was significantly upregulated in the ACHN,786-O,and SN12-PM6 cells,with the highest expression observed in 786-O cells.The results of the subcellular localization experiments indicated that ABHD11-AS1 was primarily distributed in the cytoplasm of 786-O cells.ABHD11-AS1 knockdown reduced the proliferative and invasive abilities of 786-O cells and decreased SLC6A1 mRNA and protein expression(P＜0.05).Dual-luciferase reporter gene experiments demonstrated that ABHD11-AS1 targets and binds to miR-133a-3p,which in turn binds to SLC6A1.Overexpression of miR-133a-3p reduced the mRNA and protein levels of SLC6A1 in 786-O cells,whereas downregulation of miR-133a-3p had the opposite effect.Downregulation of miR-133a-3p enhanced the proliferation and invasion of 786-O cells,while knockdown of SLC6A1 partially reversed the promoting effect of miR-133a-3p downreg-ulation on the proliferation and invasion of 786-O cells(P＜0.05).Simultaneously,downregulation of miR-133a-3p could also partially reverse the inhibitory effects of ABHD11-AS1 knockdown on 786-O cell proliferation,invasion,and SLC6A1 expression(P＜0.05).Con-clusion ABHD11-AS1 exerts a pro-cancer effect on ccRCC by regulating the miR-133a-3p/SLC6A1 axis,which influences the prolifera-tion and invasion of renal cancer cells.

CELF1 is a multifunctional RNA-binding protein that plays important roles in growth and development by regulating gene expression.CELF1 is involved in mRNA splicing,stability,and regulation of translation,and affects cell proliferation,apoptosis,and cell-cycle processes.In recent years,CELF1 has been implicated in the progression of several non-neoplastic diseases,such as myotonic dystrophy type 1,cardiac hypertrophy,cataract,and type 2 diabetes.In addition,CELF1 is abnormally expressed in many cancers,such as colorectal cancer,hepatocellular carcinoma,non-small cell lung cancer,glioma,and breast cancer,and is closely associated with deve-lopment and drug resistance of these cancers.CELF1 is a potential target for treating diseases,but further studies are required.

Objective To investigate the protective effect and mechanism of adenosine-lidocaine-magnesium sulfate(ALM)resuscita-tion solution against acute lung injury in sepsis were investigated through in vitro and in vivo experiments.Methods ALM resuscitation solution effects on septic lung injury were assessed in SD rats and rat pulmonary micro vascular endothelial cells(PMVEC)in vitro,and the effector mechanism was explored by using network pharmacology combined with molecular biology methods,detecting alterations in nuclear factor kappaB(NF-κB)signaling pathway and inflammatory cytokine key protein expressions.Results Based on in vivo experi-ments,ALM resuscitation solution treatment significantly improved lung histopathological injury in cecal ligation and puncture(CLP)model rats,reduced the lung injury score and lung dry-to-wet ratio(P＜0.01),and significantly suppressed pro-inflammatory cytokine expressions such as that of IL-1β,IL-6,and TNF-α(P＜0.01).Moreover,in vitro experiments confirmed that ALM resuscitation solution significantly reduced p-p65 and p-IκBα protein expressions in LPS-induced PMVEC(P＜0.05),while down-regulating IL-1β,IL-6,and TNF-α protein levels(P＜0.01).Conclusion ALM resuscitation solution exerts a protective effect against acute lung injury in sepsis by inhibiting NF-κB signaling pathway activation and reducing pro-inflammatory cytokine release.

Objective To analyze the clinical characteristics and prognostic risk factors of patients with atrial fibrillation(AF)related to septic shock admitted to the intensive care unit(ICU).Methods This retrospective cohort study included 152 patients with septic shock who were admitted to the ICU between January 2020 and December 2023.Patients were categorized into AF(n=48)and non-AF(n=104)groups based on the occurrence of AF.Clinical parameters were compared between the two groups,and variables with statistically significant differences(P<0.05)were entered into a multivariate logistic regression analysis to identify clinical features associated with AF.Patients were also stratified into survival(n=103)and death(n=49)groups based on 28-day outcomes.Variables showing signifi-cant intergroup differences(P<0.05)were further included in a multivariate model to identify independent risk factors for mortality.Kaplan-Meier survival analysis was performed using AF as a binary variable,and log-rank tests were applied to compare survival curves.Results The incidence of AF was 31.58%among patients with septic shock.Compared with the non-AF group,the AF group was older,received higher cumulative doses of vasoactive agents,and had elevated levels of lactate(Lac),N-terminal brain natriuretic peptide precursor(NT-proBNP),troponin I(cTnI),tumor necrosis factorα(TNF-α),and C-reactive protein(CRP).The AF group also had higher E/e'ratios,left ventricular ejection fraction(LVEF),Acute Physiology and Chronic Health Evaluation-Ⅱ(APACHEⅡ)scores,Sequen-tial Organ Failure Assessment(SOFA)scores,and 28-day mortality rates(all P<0.05).Multivariate logistic regression identified age(odds ratio[OR]=1.060,P=0.015),SOFA score(OR=1.525,P=0.001),TNF-α(OR=1.009,P=0.026),CRP(OR=1.008,P=0.002),and E/e'(OR=1.363,P=0.023)as independent risk factors for AF.The 28-day mortality rate was 32.24%.Compared with survivors,non-survivors had significantly higher Lac,cTnI,E/e',LVEF,and TNF-α levels,higher APACHEⅡand SOFA scores,longer ICU stays,and a higher incidence of AF(all P<0.05).Multivariate analysis identified SOFA score,cTnI,E/e',and AF as independent predictors of 28-day mortality.Kaplan-Meier analysis revealed significantly poorer survival in patients with AF(χ2=6.747,P=0.009).Conclusion AF is common in ICU patients with septic shock.Advanced age,greater organ dysfunction,elevated inflammatory markers,and diastolic dysfunction are associated with AF occurrence.Organ dysfunction,myocardial injury,diastolic dysfunction,and AF are inde-pendent predictors of mortality in this population.Greater clinical attention is warranted in patients with AF and septic shock due to their elevated risk of poor outcomes.

Objective To investigate the effects of leflunomide combined with belimumab on the activity index and renal function of patients with lupus nephritis(LN).Methods A total of 82 patients with LN admitted to Tangshan Gongren Hospital from January 2022 to January 2024 were selected as study subjects and randomly divided into two groups:the combination group(belimumab+leflunomide treatment)and the control group(leflunomide treatment),with 41 patients in each group.Renal function indicators(blood urea nitrogen(BUN),serum creatinine(sCr),uric acid(UA),and 24-hour urine protein),disease activity[Systemic Lupus Erythematosus Disease Activity Index(SLEDAI)score],laboratory indicators(anti-double-stranded DNA antibody,anti-ds-DNA;C-reactive protein,CRP;tumor necrosis factor α,TNF-α),efficacy,and safety were compared before and after treatment between the two groups.Results After treatment,the levels of BUN,sCr,UA,and 24-hour urine protein in the combination group were significantly lower than those in the con-trol group(P<0.05).Furthermore,the SLEDAI score,anti-ds-DNA,CRP,and TNF-α levels in the combination group were also lower than those in the control group(P<0.05).The total effective rate in the combination group(97.56%)was higher than that in the control group(85.37%,P=0.048),despite no statistically significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion Leflunomide combined with belimumab treatment for LN can effectively improve clinical efficacy,reduce disease activity,alleviate inflammation,enhance immune function,and improve renal function,with a certain level of safety,thus making the regimen highly valuable for clinical application and promotion.