Objective:To study the effect of Yigan capsule on the expression of high mobility group protein B1(HMGB1),nuclear factor-B(NF-κB)and receptor for advanced glycation end products(RAGE)in anti-tuberculosis drug-induced...Objective:To study the effect of Yigan capsule on the expression of high mobility group protein B1(HMGB1),nuclear factor-B(NF-κB)and receptor for advanced glycation end products(RAGE)in anti-tuberculosis drug-induced liver injury(ATB-DILI),and to explore its protective effect and mechanism on ATB-DILI,so as to provide experimental basis for the clinical application of Yigan capsule.Methods:Twenty-four rats were divided into two groups.Except for the blank group(n=6),the other 18 rats were given isoniazid(INH)+rifampicin(RFP)(50 mg/kg.d)for 4 weeks.Then 18 rats were randomly divided into three groups(model group,low dose group of Yigan capsule and high dose group of Yigan capsule)according to 6 rats in each group.The blank group and the model group were given 0.9%sodium chloride solution by intragastric administration.The low dose group of Yigan capsule was 0.468 g/kg,and the high dose group of Yigan capsule was 1.872 g/kg[1].After 4 weeks,the pathological changes of liver were observed by HE staining.The contents of ALT,AST,ALP,γ-GT and TBIL were detected.The expression of HMGB1,NF-κBp65 and RAGE protein was detected by IHC.The expression levels of HMGB1,NF-κBp65,RAGE,TNF-αand IL-1βwere detected by WB.Result:HE staining showed that the structure of the liver in the model group was disordered,the liver cells showed swelling and fusion,the number of inflammatory cells increased and accompanied by punctate necrosis,while the above pathological changes in each treatment group of Yigan capsule were significantly improved.The contents of ALT,AST,ALP,γ-GT and TBIL in the model group were higher than those in the blank group(P<0.05).The contents of ALT,AST,ALP,γ-GT and TBIL in each treatment group were significantly lower than those in the model group(P<0.05).Compared with the blank group,the expression levels of TNF-αand IL-1βin the model group were increased(P<0.05),and the expression levels of HMGB1,NF-κBp65 and RAGE were increased(P<0.05).Compared with the model group,the expression levels of TNF-αand IL-1βin each treatment group of Yigan capsule decreased(P<0.05),and the expression of HMGB1,NF-κBp65 and RAGE decreased(P<0.05).Conclusion:Yigan capsule may inhibit the secretion of inflammatory factors through HMGB1/RAGE/NF-κBp65 signaling pathway,thus protecting ATB-DILI.展开更多
微粒体谷胱甘肽S-转移酶1(microsomal glutathione S-transferase 1,MGST1)是谷胱甘肽S-转移酶(glutathione S-transferase,GST)超家族和花生四烯酸与谷胱甘肽代谢中的膜相关蛋白(membrane-associated proteins in eicosanoid and gluta...微粒体谷胱甘肽S-转移酶1(microsomal glutathione S-transferase 1,MGST1)是谷胱甘肽S-转移酶(glutathione S-transferase,GST)超家族和花生四烯酸与谷胱甘肽代谢中的膜相关蛋白(membrane-associated proteins in eicosanoid and glutathione metabolism,MAPEG)超家族的共同成员,它通过催化外源性物质的II相解毒过程,从而保护细胞膜免受氧化应激的损伤。众多研究发现MGST1与恶性肿瘤的发生发展密切相关,有望成为癌症治疗的新型分子靶点。本文就MGST1在恶性肿瘤中的研究进展予以综述。展开更多
Objective:Definitive chemoradiotherapy(dCRT)is the standard treatment for unresectable locally advanced esophageal cancer.However,this treatment is associated with substantial toxicity,and most malnourished or elderly...Objective:Definitive chemoradiotherapy(dCRT)is the standard treatment for unresectable locally advanced esophageal cancer.However,this treatment is associated with substantial toxicity,and most malnourished or elderly patients are unable to complete this therapy.Therefore,there is a need for a more suitable radiotherapy combination regimen for this population.This study was aimed to evaluate the efficacy and safety of a combination regimen comprising chemotherapy with nimotuzumab and S-1 and concurrent radiotherapy for patients with fragile locally advanced esophageal cancer with a high Nutritional Risk Screening 2002(NRS-2002)score.Methods:Eligible patients with unresectable esophageal carcinoma who had an NRS-2002 score of 2 or higher were enrolled.They were treated with S-1 and nimotuzumab with concurrent radiotherapy,followed by surgery or definitive radiotherapy.The primary endpoint was the locoregional control(LRC)rate.Results:A total of 55 patients who met the study criteria were enrolled.After completion of treatment,surgery was performed in 15 patients and radiotherapy was continued in 40 patients.The median follow-up period was 33.3[95%confidence interval(95%CI,31.4−35.1)]months.The LRC rate was 77.2%(95%CI,66.6%−89.4%)at 1 year in the entire population.The overall survival(OS)rate and event-free survival(EFS)rate were 57.5%and 51.5%at 3 years,respectively.Surgery was associated with better LRC[hazard ratio(HR)=0.16;95%CI,0.04−0.70;P=0.015],OS(HR=0.19;95%CI,0.04−0.80;P=0.024),and EFS(HR=0.25;95%CI,0.08−0.75;P=0.013).Most adverse events were of grade 1 or 2,and no severe adverse events occurred.Conclusions:For malnourished or elderly patients with locally advanced esophageal cancer,radiotherapy combined with nimotuzumab and S-1 is effective and has a good safety profile.展开更多
Objective:To investigate the regulatory effect of Qiliqiangxin Capsule on mitochondrial Ca^(2+)related genes in rats with myocardial infarction(MI).Methods:The rat model of MI was established by ligation of the left a...Objective:To investigate the regulatory effect of Qiliqiangxin Capsule on mitochondrial Ca^(2+)related genes in rats with myocardial infarction(MI).Methods:The rat model of MI was established by ligation of the left anterior descending coronary artery.After operation,the rats were randomly assigned to the model group,the Qiliqiangxin group and the captopril group;a sham-operated group was also available as a control.After four weeks of treatment,the extent of infarction in rats was observed by gross cardiac structure and the morphological changes of myocardial histopathology were observed by HE staining.Detection of mitochondrial Ca^(2+)transport-related genes such as inositol-1,4,5-trisphosphate receptor 2(IP3R2),glucose regulated protein 75(GRP75),voltage-dependent anion channel 1(VDAC1),and mitofusion 2(Mfn2)and mitochondrial apoptosis-related genes such as B-cell lymphoma-2(Bcl-2)and Bcl-2 related X protein(Bax)mRNA expression changes was measured by RT-PCR in the infarct margins of the heart;Western blot was used to detect changes in Bcl-2,Bax protein expression in myocardial tissue.The rate of apoptosis in cardiac myocardial tissue was detected by TUNEL staining.Results:Compared with the sham group,the anterior left ventricular wall of the model group showed a large area of infarction,and the structure of myocardial tissue was disordered.The mRNA expression level of mitochondrial Ca^(2+)transport-related genes such as IP3R2,GRP75,VDAC1,and Mfn2 were significantly increased(P<0.05,P<0.01);The mRNA and protein expression of Bcl-2,a molecule related to mitochondrial apoptosis,were significantly decreased(P<0.01),while the mRNA and protein expression of Bax were significantly increased(P<0.01);and apoptosis rate was significantly increased(P<0.01).Compared with the model group,the infarct size of cardiac gross specimens in the Qiliqiangxin group and the captopril group was reduced and myocardial fibers were relatively well ordered;The mRNA expression of mitochondrial Ca^(2+)transport-related genes such as IP3R2,GRP75,VDAC1,and Mfn2 were significantly reduced(P<0.01);the mRNA and protein expression of Bcl-2,a molecule related to mitochondrial apoptosis,were increased(P<0.05,P<0.01),and the mRNA and protein expression of Bax were significantly decreased(P<0.05,P<0.01).and apoptosis rate was significantly decreased(P<0.01).Conclusion:Qiliqiangxin Capsule can improve the morphological structure of the heart of rats with MI,and its mechanism is related to regulation of the gene expression of mitochondrial Ca^(2+)transport complex IP3R2/GRP75/VDAC1,thereby inhibiting apoptosis.展开更多
OBJECTIVE: To investigate the effects of Maixuekang Capsules combined with edaravone on serum matrix metalloproteinase-9(MMP-9), S-100β protein levels and neurological functions in patients with hemorrhagic cerebral ...OBJECTIVE: To investigate the effects of Maixuekang Capsules combined with edaravone on serum matrix metalloproteinase-9(MMP-9), S-100β protein levels and neurological functions in patients with hemorrhagic cerebral infarction. METHOSDS: A total of 76 patients with hemorrhagic cerebral infarction treated in the First Affiliated Hospital of Henan University of Science and Technology from January 2017 to May 2018 were selected and were randomly divided into treatment group and control group, with 38 patients in each group. The control group was given edaravone, and the treatment group was given Maixuekang Capsules on the basis of the control group. The clinical efficacy, serum MMP-9 and S-100β protein levels, neurological function recovery, activity of daily living and incidence rate of adverse reactions were compared between the 2 groups. RESULTS: The total effective rate of the treatment group was 92.11%, which was higher than 71.05% of the control group(P < 0.05); the National Institutes of Health Stroke Scale(NIHSS) score in the 2 groups decreased(P < 0.05), and the Activity of Daily Living Scale(ADL) score increased(P < 0.05), the improvement of the above 2 scores in the treatment group were better than those in the control group(P < 0.05); the level of MMP-9 was gradually decreasing in the 2 groups, on the 7th day, 14 th day after treatment, and the levels of MMP-9 decreased significantly(P < 0.05), and the treatment group was lower than the control group at all time points(P < 0.05); on the 3rd day after treatment, the levels of S-100β protein in the 2 groups increased significantly(P < 0.05); on the 7th day, 14 th day after treatment, the levels of S-100β protein in the two groups decreased significantly(P < 0.05), and the treatment group was significantly lower than the control group(P < 0.05); there was no significant difference in incidence rate of adverse reactions between 7.89% in the control group and 5.26% in the treatment group(P > 0.05). CONCLUSION: The combination of Maixuekang Capsules and edaravone is effective in treating hemorrhagic cerebral infarction, and it can significantly improve neurological function defect and daily living ability, reduce serum MMP-9 and S-100β protein levels, and has higher safety.展开更多
Objective: The aim of this study was to evaluate the efficacy and safety profile of DeFazio (S-l) combined with oxaliplatin against unresectable advanced or metastatic gastric cancer. Methods: Oxaliplatin was give...Objective: The aim of this study was to evaluate the efficacy and safety profile of DeFazio (S-l) combined with oxaliplatin against unresectable advanced or metastatic gastric cancer. Methods: Oxaliplatin was given intravenously at 130 mg/m2 for 2 h on dl and S-1 was administered bid. at 80 mg/m2/day on d1-14 followed by a 7-day rest during the 3-week schedule. Results: All 62 patients were assessed for efficacy and adverse events. The response and disease control rates were 47.3% and 80.8%, respectively. The median time to progression was 7.8 months, and the median overall survival was 11.6 months. The grade 3/4 adverse events were hematological toxicities, including neutropenia (11.3%), thrombocytopenia (9.7%) and gastrointestinal reactions (6.5%). Conclusion: The SOX regimen (oxaliplatin, 130 mg/m2 d l; S-1, 80 mg/m2/day, bid. d1-14, q3w) provide a favorable efficacy and safety profile in patients with advanced gastric cancer.展开更多
基金Scientific Research Project of Heilongjiang Provincial Education Department(No.12531608)。
文摘Objective:To study the effect of Yigan capsule on the expression of high mobility group protein B1(HMGB1),nuclear factor-B(NF-κB)and receptor for advanced glycation end products(RAGE)in anti-tuberculosis drug-induced liver injury(ATB-DILI),and to explore its protective effect and mechanism on ATB-DILI,so as to provide experimental basis for the clinical application of Yigan capsule.Methods:Twenty-four rats were divided into two groups.Except for the blank group(n=6),the other 18 rats were given isoniazid(INH)+rifampicin(RFP)(50 mg/kg.d)for 4 weeks.Then 18 rats were randomly divided into three groups(model group,low dose group of Yigan capsule and high dose group of Yigan capsule)according to 6 rats in each group.The blank group and the model group were given 0.9%sodium chloride solution by intragastric administration.The low dose group of Yigan capsule was 0.468 g/kg,and the high dose group of Yigan capsule was 1.872 g/kg[1].After 4 weeks,the pathological changes of liver were observed by HE staining.The contents of ALT,AST,ALP,γ-GT and TBIL were detected.The expression of HMGB1,NF-κBp65 and RAGE protein was detected by IHC.The expression levels of HMGB1,NF-κBp65,RAGE,TNF-αand IL-1βwere detected by WB.Result:HE staining showed that the structure of the liver in the model group was disordered,the liver cells showed swelling and fusion,the number of inflammatory cells increased and accompanied by punctate necrosis,while the above pathological changes in each treatment group of Yigan capsule were significantly improved.The contents of ALT,AST,ALP,γ-GT and TBIL in the model group were higher than those in the blank group(P<0.05).The contents of ALT,AST,ALP,γ-GT and TBIL in each treatment group were significantly lower than those in the model group(P<0.05).Compared with the blank group,the expression levels of TNF-αand IL-1βin the model group were increased(P<0.05),and the expression levels of HMGB1,NF-κBp65 and RAGE were increased(P<0.05).Compared with the model group,the expression levels of TNF-αand IL-1βin each treatment group of Yigan capsule decreased(P<0.05),and the expression of HMGB1,NF-κBp65 and RAGE decreased(P<0.05).Conclusion:Yigan capsule may inhibit the secretion of inflammatory factors through HMGB1/RAGE/NF-κBp65 signaling pathway,thus protecting ATB-DILI.
基金supported by grants from Beijing Xisike Clinical Oncology Research Foundation(No.YYoung2023-0114).
文摘Objective:Definitive chemoradiotherapy(dCRT)is the standard treatment for unresectable locally advanced esophageal cancer.However,this treatment is associated with substantial toxicity,and most malnourished or elderly patients are unable to complete this therapy.Therefore,there is a need for a more suitable radiotherapy combination regimen for this population.This study was aimed to evaluate the efficacy and safety of a combination regimen comprising chemotherapy with nimotuzumab and S-1 and concurrent radiotherapy for patients with fragile locally advanced esophageal cancer with a high Nutritional Risk Screening 2002(NRS-2002)score.Methods:Eligible patients with unresectable esophageal carcinoma who had an NRS-2002 score of 2 or higher were enrolled.They were treated with S-1 and nimotuzumab with concurrent radiotherapy,followed by surgery or definitive radiotherapy.The primary endpoint was the locoregional control(LRC)rate.Results:A total of 55 patients who met the study criteria were enrolled.After completion of treatment,surgery was performed in 15 patients and radiotherapy was continued in 40 patients.The median follow-up period was 33.3[95%confidence interval(95%CI,31.4−35.1)]months.The LRC rate was 77.2%(95%CI,66.6%−89.4%)at 1 year in the entire population.The overall survival(OS)rate and event-free survival(EFS)rate were 57.5%and 51.5%at 3 years,respectively.Surgery was associated with better LRC[hazard ratio(HR)=0.16;95%CI,0.04−0.70;P=0.015],OS(HR=0.19;95%CI,0.04−0.80;P=0.024),and EFS(HR=0.25;95%CI,0.08−0.75;P=0.013).Most adverse events were of grade 1 or 2,and no severe adverse events occurred.Conclusions:For malnourished or elderly patients with locally advanced esophageal cancer,radiotherapy combined with nimotuzumab and S-1 is effective and has a good safety profile.
基金This study was supported by Beijing University of Traditional Chinese Medicine Dongzhimen Hospital 2022 Science and Technology Innovation Special Project(DZMKJCX-2022-008)。
文摘Objective:To investigate the regulatory effect of Qiliqiangxin Capsule on mitochondrial Ca^(2+)related genes in rats with myocardial infarction(MI).Methods:The rat model of MI was established by ligation of the left anterior descending coronary artery.After operation,the rats were randomly assigned to the model group,the Qiliqiangxin group and the captopril group;a sham-operated group was also available as a control.After four weeks of treatment,the extent of infarction in rats was observed by gross cardiac structure and the morphological changes of myocardial histopathology were observed by HE staining.Detection of mitochondrial Ca^(2+)transport-related genes such as inositol-1,4,5-trisphosphate receptor 2(IP3R2),glucose regulated protein 75(GRP75),voltage-dependent anion channel 1(VDAC1),and mitofusion 2(Mfn2)and mitochondrial apoptosis-related genes such as B-cell lymphoma-2(Bcl-2)and Bcl-2 related X protein(Bax)mRNA expression changes was measured by RT-PCR in the infarct margins of the heart;Western blot was used to detect changes in Bcl-2,Bax protein expression in myocardial tissue.The rate of apoptosis in cardiac myocardial tissue was detected by TUNEL staining.Results:Compared with the sham group,the anterior left ventricular wall of the model group showed a large area of infarction,and the structure of myocardial tissue was disordered.The mRNA expression level of mitochondrial Ca^(2+)transport-related genes such as IP3R2,GRP75,VDAC1,and Mfn2 were significantly increased(P<0.05,P<0.01);The mRNA and protein expression of Bcl-2,a molecule related to mitochondrial apoptosis,were significantly decreased(P<0.01),while the mRNA and protein expression of Bax were significantly increased(P<0.01);and apoptosis rate was significantly increased(P<0.01).Compared with the model group,the infarct size of cardiac gross specimens in the Qiliqiangxin group and the captopril group was reduced and myocardial fibers were relatively well ordered;The mRNA expression of mitochondrial Ca^(2+)transport-related genes such as IP3R2,GRP75,VDAC1,and Mfn2 were significantly reduced(P<0.01);the mRNA and protein expression of Bcl-2,a molecule related to mitochondrial apoptosis,were increased(P<0.05,P<0.01),and the mRNA and protein expression of Bax were significantly decreased(P<0.05,P<0.01).and apoptosis rate was significantly decreased(P<0.01).Conclusion:Qiliqiangxin Capsule can improve the morphological structure of the heart of rats with MI,and its mechanism is related to regulation of the gene expression of mitochondrial Ca^(2+)transport complex IP3R2/GRP75/VDAC1,thereby inhibiting apoptosis.
文摘OBJECTIVE: To investigate the effects of Maixuekang Capsules combined with edaravone on serum matrix metalloproteinase-9(MMP-9), S-100β protein levels and neurological functions in patients with hemorrhagic cerebral infarction. METHOSDS: A total of 76 patients with hemorrhagic cerebral infarction treated in the First Affiliated Hospital of Henan University of Science and Technology from January 2017 to May 2018 were selected and were randomly divided into treatment group and control group, with 38 patients in each group. The control group was given edaravone, and the treatment group was given Maixuekang Capsules on the basis of the control group. The clinical efficacy, serum MMP-9 and S-100β protein levels, neurological function recovery, activity of daily living and incidence rate of adverse reactions were compared between the 2 groups. RESULTS: The total effective rate of the treatment group was 92.11%, which was higher than 71.05% of the control group(P < 0.05); the National Institutes of Health Stroke Scale(NIHSS) score in the 2 groups decreased(P < 0.05), and the Activity of Daily Living Scale(ADL) score increased(P < 0.05), the improvement of the above 2 scores in the treatment group were better than those in the control group(P < 0.05); the level of MMP-9 was gradually decreasing in the 2 groups, on the 7th day, 14 th day after treatment, and the levels of MMP-9 decreased significantly(P < 0.05), and the treatment group was lower than the control group at all time points(P < 0.05); on the 3rd day after treatment, the levels of S-100β protein in the 2 groups increased significantly(P < 0.05); on the 7th day, 14 th day after treatment, the levels of S-100β protein in the two groups decreased significantly(P < 0.05), and the treatment group was significantly lower than the control group(P < 0.05); there was no significant difference in incidence rate of adverse reactions between 7.89% in the control group and 5.26% in the treatment group(P > 0.05). CONCLUSION: The combination of Maixuekang Capsules and edaravone is effective in treating hemorrhagic cerebral infarction, and it can significantly improve neurological function defect and daily living ability, reduce serum MMP-9 and S-100β protein levels, and has higher safety.
文摘Objective: The aim of this study was to evaluate the efficacy and safety profile of DeFazio (S-l) combined with oxaliplatin against unresectable advanced or metastatic gastric cancer. Methods: Oxaliplatin was given intravenously at 130 mg/m2 for 2 h on dl and S-1 was administered bid. at 80 mg/m2/day on d1-14 followed by a 7-day rest during the 3-week schedule. Results: All 62 patients were assessed for efficacy and adverse events. The response and disease control rates were 47.3% and 80.8%, respectively. The median time to progression was 7.8 months, and the median overall survival was 11.6 months. The grade 3/4 adverse events were hematological toxicities, including neutropenia (11.3%), thrombocytopenia (9.7%) and gastrointestinal reactions (6.5%). Conclusion: The SOX regimen (oxaliplatin, 130 mg/m2 d l; S-1, 80 mg/m2/day, bid. d1-14, q3w) provide a favorable efficacy and safety profile in patients with advanced gastric cancer.