AIM:To investigate the role and mechanisms of p21 activated kinase 1(Pak1)in myocardial met-abolic reprogramming(MR)in diabetes mellitus(DM)mice and its protective effects on cardiomyocytes.METHODS:Pak1flox/flox(Pak1f/f)mice and cardiomyocyte-specific Pak1 knockout(Pak1CKO)mice were randomly divided into 4 groups(n=6 per group):Pak1f/f group,Pak1f/f+DM group,Pak1CKO group,and Pak1CKO+DM group.Diabetes was induced by in-traperitoneal injection of streptozotocin.Cardiac function was evaluated by echocardiography 6 weeks after successful mod-eling.Ventricular myocardium was harvested after euthanasia.Myocardial pathological changes and lipid accumulation were assessed by HE staining and oil red O staining.Protein expression levels of Pak1,p-Pak1,peroxisome proliferator-activated receptor α(PPARα),PPARγ,lipoprotein lipase(LPL),carnitine palmitoyltransferase 1(CPT1),scavenger receptor B2(SCARB2/CD36),fatty acid binding protein 3(FABP3),pyruvate dehydrogenase kinase 4(PDK4)and the ratio of phosphorylated pyruvate dehydrogenase E1α subunit(p-PDHA1)to PDHA1 were determined by Western blot.The mRNA expression levels of diacylglycerol acyltransferase 1/2(DGAT1/2)were detected by RT-qPCR.RESULTS:Compared with Pak1f/f group,both Pak1f/f+DM and Pak1CKO groups showed significantly decreased left ventricular ejection fraction(EF)and fractional shortening(FS),as well as increased left ventricular end-diastolic volume(LV Vold)and end-systolic volume(LV Vols)(P<0.01).Significant myocardial pathological damage with excessive lipid accumulation was observed.Myocardial p-Pak1 and Pak1 protein expression decreased(P<0.01),while PPARα,PPARγ,CPT1,LPL,CD36,FABP3,and PDK4 protein expression significantly increased(P<0.01),along with elevated p-PDHA1/PDHA1 ratio(P<0.01).mRNA expression levels of DGAT1 and DGAT2 were significantly reduced(P<0.01).The Pak1CKO+DM group showed the same trend as the Pak1f/f+DM group but with greater severity;compared with the Pak1f/f+DM group,the Pak1CKO+DM group still showed significant differences in all indicators except EF,FS,and LVVold(P<0.05 or P<0.01).CONCLUSION:Myocardial Pak1 protein expression is suppressed in diabetic mice,which mediates MR through activation of the PPARα/γ signaling pathway,resulting in increased myocardial fatty acid uptake and utiliza-tion while reducing glucose oxidation capacity.This leads to lipid accumulation in cardiomyocytes,myocardial damage,and cardiac systolic and diastolic dysfunction.

AIM:To investigate the role and mechanisms of p21 activated kinase 1(Pak1)in myocardial met-abolic reprogramming(MR)in diabetes mellitus(DM)mice and its protective effects on cardiomyocytes.METHODS:Pak1flox/flox(Pak1f/f)mice and cardiomyocyte-specific Pak1 knockout(Pak1CKO)mice were randomly divided into 4 groups(n=6 per group):Pak1f/f group,Pak1f/f+DM group,Pak1CKO group,and Pak1CKO+DM group.Diabetes was induced by in-traperitoneal injection of streptozotocin.Cardiac function was evaluated by echocardiography 6 weeks after successful mod-eling.Ventricular myocardium was harvested after euthanasia.Myocardial pathological changes and lipid accumulation were assessed by HE staining and oil red O staining.Protein expression levels of Pak1,p-Pak1,peroxisome proliferator-activated receptor α(PPARα),PPARγ,lipoprotein lipase(LPL),carnitine palmitoyltransferase 1(CPT1),scavenger receptor B2(SCARB2/CD36),fatty acid binding protein 3(FABP3),pyruvate dehydrogenase kinase 4(PDK4)and the ratio of phosphorylated pyruvate dehydrogenase E1α subunit(p-PDHA1)to PDHA1 were determined by Western blot.The mRNA expression levels of diacylglycerol acyltransferase 1/2(DGAT1/2)were detected by RT-qPCR.RESULTS:Compared with Pak1f/f group,both Pak1f/f+DM and Pak1CKO groups showed significantly decreased left ventricular ejection fraction(EF)and fractional shortening(FS),as well as increased left ventricular end-diastolic volume(LV Vold)and end-systolic volume(LV Vols)(P<0.01).Significant myocardial pathological damage with excessive lipid accumulation was observed.Myocardial p-Pak1 and Pak1 protein expression decreased(P<0.01),while PPARα,PPARγ,CPT1,LPL,CD36,FABP3,and PDK4 protein expression significantly increased(P<0.01),along with elevated p-PDHA1/PDHA1 ratio(P<0.01).mRNA expression levels of DGAT1 and DGAT2 were significantly reduced(P<0.01).The Pak1CKO+DM group showed the same trend as the Pak1f/f+DM group but with greater severity;compared with the Pak1f/f+DM group,the Pak1CKO+DM group still showed significant differences in all indicators except EF,FS,and LVVold(P<0.05 or P<0.01).CONCLUSION:Myocardial Pak1 protein expression is suppressed in diabetic mice,which mediates MR through activation of the PPARα/γ signaling pathway,resulting in increased myocardial fatty acid uptake and utiliza-tion while reducing glucose oxidation capacity.This leads to lipid accumulation in cardiomyocytes,myocardial damage,and cardiac systolic and diastolic dysfunction.

Background and purpose:Lobaplatin,as a traditional chemotherapeutic drug,is widely used in the treatment of malignant tumor.In recent years,its application in the field of hyperthermic intraperitoneal chemotherapy(HIPEC)has garnered increasing attention.This study evaluated the efficacy and safety of lobaplatin-based HIPEC in advanced abdominal metastatic cancer.Methods:This study collected data of patients with advanced cancers and malignant ascites who treated in the Cancer Center of Shanghai Tenth People's Hospital,Tongji University School of Medicine,from January 2019 to January 2023.We excluded patients who did not meet the inclusion criteria.Short-term efficacy was assessed by changes in ascitic fluid volume,and long-term survival was analyzed using the Kaplan-Meier method.The correlation between CA12-5 levels before and after treatment was evaluated using Pearson correlation analysis.Baseline characteristics and treatment outcomes were described using descriptive statistics,and the changes in CA12-5 levels before and after treatment were compared using significance tests(P＜0.01).Data entry and statistical analyses were conducted using SPSS version 26.0,and survival curves and efficacy plots were generated with GraphPad Prism(10.4.0 version).The study was approved by the Ethics Committee of Shanghai Tenth People's Hospital(Ethics approval number:SHSY-IEC-5.0/24K134/P01).This prospective single-arm study strictly adhered to the guideline of Consolidated Standards of Reporting Trials(CONSORT)checklist.Results:A total of 21 patients were enrolled in this study.The median age of the patients was 61 years(ranging from 31 to 71 years).Among the 21 patients,5(23.8%)achieved complete remission(CR),5(23.8%)achieved partial remission(PR),8(38.1%)had stable disease(SD),and 3(14.3%)experienced disease progression(PD).The overall response rate(ORR)was 47.6%,and the disease control rate(DCR)was 85.7%.Survival analysis revealed a median progression-free survival(PFS)of 12.33 months and a median overall survival(OS)of 16.37 months.Analysis of tumor markers showed a significant negative correlation between efficacy and CA12-5 levels(P＜0.01).Adverse reactions primarily included myelosuppression,hepatic and renal impairment,and nausea and vomiting,with most adverse events being mild to moderate.Conclusion:Lobaplatin-based HIPEC is effective in the treatment of advanced gastrointestinal malignancies with malignant ascites,providing survival benefits and demonstrating good safety.CA12-5 may serve as a valuable predictor of poor prognosis.

Background and purpose:Lobaplatin,as a traditional chemotherapeutic drug,is widely used in the treatment of malignant tumor.In recent years,its application in the field of hyperthermic intraperitoneal chemotherapy(HIPEC)has garnered increasing attention.This study evaluated the efficacy and safety of lobaplatin-based HIPEC in advanced abdominal metastatic cancer.Methods:This study collected data of patients with advanced cancers and malignant ascites who treated in the Cancer Center of Shanghai Tenth People's Hospital,Tongji University School of Medicine,from January 2019 to January 2023.We excluded patients who did not meet the inclusion criteria.Short-term efficacy was assessed by changes in ascitic fluid volume,and long-term survival was analyzed using the Kaplan-Meier method.The correlation between CA12-5 levels before and after treatment was evaluated using Pearson correlation analysis.Baseline characteristics and treatment outcomes were described using descriptive statistics,and the changes in CA12-5 levels before and after treatment were compared using significance tests(P＜0.01).Data entry and statistical analyses were conducted using SPSS version 26.0,and survival curves and efficacy plots were generated with GraphPad Prism(10.4.0 version).The study was approved by the Ethics Committee of Shanghai Tenth People's Hospital(Ethics approval number:SHSY-IEC-5.0/24K134/P01).This prospective single-arm study strictly adhered to the guideline of Consolidated Standards of Reporting Trials(CONSORT)checklist.Results:A total of 21 patients were enrolled in this study.The median age of the patients was 61 years(ranging from 31 to 71 years).Among the 21 patients,5(23.8%)achieved complete remission(CR),5(23.8%)achieved partial remission(PR),8(38.1%)had stable disease(SD),and 3(14.3%)experienced disease progression(PD).The overall response rate(ORR)was 47.6%,and the disease control rate(DCR)was 85.7%.Survival analysis revealed a median progression-free survival(PFS)of 12.33 months and a median overall survival(OS)of 16.37 months.Analysis of tumor markers showed a significant negative correlation between efficacy and CA12-5 levels(P＜0.01).Adverse reactions primarily included myelosuppression,hepatic and renal impairment,and nausea and vomiting,with most adverse events being mild to moderate.Conclusion:Lobaplatin-based HIPEC is effective in the treatment of advanced gastrointestinal malignancies with malignant ascites,providing survival benefits and demonstrating good safety.CA12-5 may serve as a valuable predictor of poor prognosis.

Objective:To detect the expression levels of neuropilin1 (NRP1)mRNA and miR-9 in non-small cell lung cancer (NSCLC)tissue samples, and to explore the correlations between the expressions of NRP1 mRNA, miR-9 and the clinicopathological characteristics of the patients with NSCLC.Methods:Informed consent was obtained from each patient before surgery.The tissue samples including 45 NSCLC tissue ,45 adjacent carcinoma tissue and 45 normal lung tissue were collected from China-Japan Union Hospital of Jilin University from 2010 to 2011.qRT-PCR was used to detect the expression levels of NRP1 mRNA and miR-9 in three kinds of lung tissue, and the correlation between the expressions of NRP1 mRNA, miR-9 and clinicopathological characteristics of the patients with NSCLC was analyzed.Results:Compared with normal tissue,the expression level of NRP1 mRNA in adjacent carcinoma tissue had no change (P>0.05),but the expression level of NRP1 mRNA in non-small cell lung cancer tissue was significantly decreased (P<0.05).Compared with normal tissue,the expression level of miR-9 in adjacent carcinoma tissue had no change (P>0.05),but the expression level of miR-9 in non-small cell lung cancer tissue was significantly increased (P < 0.05 ). Furthermore, in adjacent carcinoma tissue, the expression level of miR-9 in the males was lower than that in the females (P<0.05 ). In NSCLC tissue, the expression level of NRP1 mRNA had no relationship with sex,age,differentiation degree,TNM stage and clinical stage,but was significantly correlated to the histological subtype and lymph node metastasis (P<0.05).In NSCLC tissue,the expression level of miR-9 had no relationship with age, pathological type, lymph node metastasis, differentiation degree,TNM stage,and clinical stage (P>0.05),but was correlated to the sex (P<0.05). Conclusion:The expression level of miR-9 is up-regulated and the expression level of NRP1 mRNA is down-regulated significantly in non-small cell lung cancer tissue. The detection of the expression level of NRP1 mRNA contributes to j udge the histological subtype and lymph node metastasis of NSCLC.

This study was aimed to evaluate the hemostatic effect and mechanism of action for water decoction of Blumea megacephala (Randeria) Chang et Tseng in order to understand its influence to the liver function. The glass slides method and capillary tube method were used in the measurement of the coagulation time (CT). And the tail-cutting method was used to measure the bleeding time (BT), prothrombin time (PT), activated part clotting live en-zyme time (APTT), thrombin time (TT), content of plasma fibrinogen (FIB), platelet count (PLC), plasma complex cal-cium time (PRT), alanine aminotransferase (ALT) and aspartate transaminase (AST). The results showed that intragastric administration with different doses of water decoction of Blumea megacephala (Randeria) Chang et Tseng (6.7 g·kg-1, 13.4 g·kg-1, 26.8 g·kg-1) can reduce CT and BT of mice. And intragastric administration with different doses of wa-ter decoction of Blumea megacephala (Randeria) Chang et Tseng (4.7 g·kg-1, 9.4 g·kg-1, 18.9 g·kg-1) can produce different degrees of impact on PT, APTT, TT and PRT of rats. Certain dose of water decoction of Blumea megacepha-la (Randeria) Chang et Tseng can reduce ALT and AST. It was concluded that Blumea megacephala (Randeria) Chang et Tseng had the hemostatic effect and its mechanism of action may be through the activation of the intrinsic and extrinsic coagulation system. There was no obvious damage to the liver.