Objective To investigate the mechanism of kaempferol(KPF)in the treatment of macular edema sec-ondary to retinal vein occlusion(RVO-ME).Methods RVO model was established in SD rats using photocoagulation.Twenty SD rats were randomly divided into:Control group(normal rats,saline injection),Model group(RVO model rats,saline injection),Low KPF group[RVO model rats,KPF injection(8 mg·kg-1·d-1)],High KPF group[RVO model rats,KPF injection(16 mg·kg-1·d-1)],with 5 rats per group for 14 days.Fundus photography observed retinal vessels;HE staining evaluated retinal structural changes.HRMECs were randomly divided into:control group(no intervention),CoCl2 group(300 μmol·L-1 CoCl2),Low-dose KPF group(300 μmol·L-1 CoCl2+20 μmol·L-1 KPF),High-dose KPF group(300 μmol·L-1 CoCl2+30 μmol·L-1 KPF)and pathway inhibitor group(DAPT group)(300 μmol·L-1 CoCl2+20 μmol·L-1 DAPT),with 24-hour intervention.CCK-8 assay detected cell viability;Scratch test measured cell migration rate;ELISA quantified inflammatory factors[interleukin(IL)-6,tumor necrosis factor(TNF)-α];FITC-dextran assay evalu-ated endothelial monolayer permeability;Immunofluorescence detected zonula occludens(ZO)-1 expression;Western blot and RT-PCR measured protein and mRNA levels of ZO-1,Occludin,Notch1,and Hes1.Results Fundus photography showed interrupted venous blood flow and retinal edema in Model group,alleviated by KPF.HE staining revealed disorder-ed retinal arrangement and severe edema in the Model group,improved by KPF.Compared with CoCl2 group,Low-and High-dose KPF groups showed reduced cell migration rate,increased cell vitality(both P＜0.05),IL-6 and TNF-α levels de-creased in Low-and High-dose KPF groups and DAPT group(all P＜0.05),permeability coefficient decreased in Low-and High-dose KPF groups and DAPT group(all P＜0.05),ZO-1 expression increased in Low-and High-dose KPF groups and DAPT group(all P＜0.05),ZO-1 and Occludin protein/mRNA levels increased;Notch1 and Hes1 protein/mRNA levels de-creased in Low-and High-dose KPF groups and DAPT group(all P＜0.05).Conclusion KPF treat RVO-ME by inhibiting the Notch1/Hes1 pathway,exerting anti-inflammatory effects and improving intercellular tight junctions.

Objective To investigate the mechanism of kaempferol(KPF)in the treatment of macular edema sec-ondary to retinal vein occlusion(RVO-ME).Methods RVO model was established in SD rats using photocoagulation.Twenty SD rats were randomly divided into:Control group(normal rats,saline injection),Model group(RVO model rats,saline injection),Low KPF group[RVO model rats,KPF injection(8 mg·kg-1·d-1)],High KPF group[RVO model rats,KPF injection(16 mg·kg-1·d-1)],with 5 rats per group for 14 days.Fundus photography observed retinal vessels;HE staining evaluated retinal structural changes.HRMECs were randomly divided into:control group(no intervention),CoCl2 group(300 μmol·L-1 CoCl2),Low-dose KPF group(300 μmol·L-1 CoCl2+20 μmol·L-1 KPF),High-dose KPF group(300 μmol·L-1 CoCl2+30 μmol·L-1 KPF)and pathway inhibitor group(DAPT group)(300 μmol·L-1 CoCl2+20 μmol·L-1 DAPT),with 24-hour intervention.CCK-8 assay detected cell viability;Scratch test measured cell migration rate;ELISA quantified inflammatory factors[interleukin(IL)-6,tumor necrosis factor(TNF)-α];FITC-dextran assay evalu-ated endothelial monolayer permeability;Immunofluorescence detected zonula occludens(ZO)-1 expression;Western blot and RT-PCR measured protein and mRNA levels of ZO-1,Occludin,Notch1,and Hes1.Results Fundus photography showed interrupted venous blood flow and retinal edema in Model group,alleviated by KPF.HE staining revealed disorder-ed retinal arrangement and severe edema in the Model group,improved by KPF.Compared with CoCl2 group,Low-and High-dose KPF groups showed reduced cell migration rate,increased cell vitality(both P＜0.05),IL-6 and TNF-α levels de-creased in Low-and High-dose KPF groups and DAPT group(all P＜0.05),permeability coefficient decreased in Low-and High-dose KPF groups and DAPT group(all P＜0.05),ZO-1 expression increased in Low-and High-dose KPF groups and DAPT group(all P＜0.05),ZO-1 and Occludin protein/mRNA levels increased;Notch1 and Hes1 protein/mRNA levels de-creased in Low-and High-dose KPF groups and DAPT group(all P＜0.05).Conclusion KPF treat RVO-ME by inhibiting the Notch1/Hes1 pathway,exerting anti-inflammatory effects and improving intercellular tight junctions.

OBJECTIVE： To provide experience and reference for the study of medical insurance budget impact analysis （BIA） in China. METHODS： Retrieved from PubMed， ProQuest， CNKI， Wanfang database and CBM， related literatures about medical insurance BIA research in China and the United States were collected since the establishment of the database. The basic information， analysis results and data sources were summarized and sorted out， and descriptive analysis of the included literature was carried out on basis of seven key elements such as model design， research perspective， treatment cost， reference scenario， target population， research time limit and discount/inflation， sensitivity analysis. RESULTS： A total of 72 literatures were included in this study， involving 24 （33.33％） studies in China， 48 （66.67％） studies in the United States； the indications of 45 studies were chronic diseases （62.50％）， and those of 21 studies were acute diseases （37.50％）. Among the research methods， 49 studies （68.06％） used BIA alone and 23 studies （31.94％） adopted BIA combined with pharmaceutical economics. In terms of model design， 50 studies （69.44％） adopted cost calculation models. In terms of research perspective， 60 studies （81.94％） were based on the perspective of medical insurance department research. In the calculation of treatment cost， 69 studies （95.84％） included drug cost. In terms of reference scenarios， 61 studies （84.72％） compared the economics of different drug-based treatment groups. For target population， only 31  （43.06％） studies used real world data. In terms of research duration and discount/inflation， 14 studies （19.44％） used treatment or length of hospitalization to indicate research duration， and 19 studies （26.39％） used discount rate or inflation rate to adjust costs. As for sensitivity analysis， 62 studies （86.11％） conducted sensitivity analysis， of which 49 （68.06％） used single factor sensitivity analysis. CONCLUSIONS： There are still some limitations in medical insurance BIA research literature in China and the United States， such as unreasonable use of data， incomplete coverage of the cost， and unreasonable setting of sensitivity analysis variables. It is recommended that BIA research should standardize data sources to improve the quality of budget evidence quality， reasonably evaluate market size to improve the authenticity of prediction， scientifically set variables and their scope of change to improve the stability of results， establish BIA research paradigms or evaluating standards so as to guide BIA research scientifically.

Objective To evaluate the cardiac safety of trastuzumab﹣containing regimens in patients with HER2﹣positive tumors. Methods The clinical data of adult patients with HER2﹣positive breast cancer,gastric cancer or gastroesophageal junction adenocarcinoma,with normal electrocardiogram and echocardiography before treatments,and treated with trastuzumab﹣containing regimens in Zhongshan Hospital Affiliated to Fudan University from January 2016 to February 2018 were collected through the hospital information system and cardiac adverse events after trastuzumab﹣containing regimens were retrospectively analyzed. ,The patients were divided into 4 groups according to the application history of antineoplastic drugs:group A ( neither anthracyclines nor fluoropyrimidines application history ), group B ( only anthracyclines application history),group C( only fluoropyrimidines application history),and group D (both anthracyclines and fluoropyrimidines application history). The occurrences of cardiac adverse events in the 4 groups were compared. Results A total of 90 patients were enrolled,including 34 males and 56 females,aged(60 ± 12)years. Of them,43 patients(47. 8% )were with breast cancer,46(51. 1% ) were with gastric cancer,and 1(1. 1% )was with gastroesophageal junction adenocarcinoma. Group A,B, C,and D comprised 11,20,52,and 7 patients,respectively. Of the 90 patients,65 patients developed 96 cases of adverse cardiac events. The incidence of adverse cardiac events was 72. 2% . The severity of cardiac adverse events was grade 1 in 91 cases and grade 2 in 5 cases. The adverse events with higher incidence were arrhythmia( 36. 7% ,33/90 ),abnormal cardiac structure ( 22. 2% ,20/90 ), valvular reflux (22. 2% ,20/90),and increased pulmonary arterial systolic pressure( 10. 0% ,9/90 ). There was no significant difference in the incidence of cardiac adverse events after trastuzumab treatment in patients with different antineoplastic drug application history among the 4 groups(all P﹥0. 05). Except for 2 patients with grade 2 sinus tachycardia whose heart rate returned to normal after treatment with beta﹣blocker,the other 63 patients did not need medical intervention. Conclusion The incidence of cardiac adverse events of trastuzumab treatment in patients with HER2﹣positive tumors was higher,but the severity of most of them were grade 1,which rarely cause serious cardiac functional or structural damage.

Objective To evaluate the cardiac safety of trastuzumab﹣containing regimens in patients with HER2﹣positive tumors. Methods The clinical data of adult patients with HER2﹣positive breast cancer,gastric cancer or gastroesophageal junction adenocarcinoma,with normal electrocardiogram and echocardiography before treatments,and treated with trastuzumab﹣containing regimens in Zhongshan Hospital Affiliated to Fudan University from January 2016 to February 2018 were collected through the hospital information system and cardiac adverse events after trastuzumab﹣containing regimens were retrospectively analyzed. ,The patients were divided into 4 groups according to the application history of antineoplastic drugs:group A ( neither anthracyclines nor fluoropyrimidines application history ), group B ( only anthracyclines application history),group C( only fluoropyrimidines application history),and group D (both anthracyclines and fluoropyrimidines application history). The occurrences of cardiac adverse events in the 4 groups were compared. Results A total of 90 patients were enrolled,including 34 males and 56 females,aged(60 ± 12)years. Of them,43 patients(47. 8% )were with breast cancer,46(51. 1% ) were with gastric cancer,and 1(1. 1% )was with gastroesophageal junction adenocarcinoma. Group A,B, C,and D comprised 11,20,52,and 7 patients,respectively. Of the 90 patients,65 patients developed 96 cases of adverse cardiac events. The incidence of adverse cardiac events was 72. 2% . The severity of cardiac adverse events was grade 1 in 91 cases and grade 2 in 5 cases. The adverse events with higher incidence were arrhythmia( 36. 7% ,33/90 ),abnormal cardiac structure ( 22. 2% ,20/90 ), valvular reflux (22. 2% ,20/90),and increased pulmonary arterial systolic pressure( 10. 0% ,9/90 ). There was no significant difference in the incidence of cardiac adverse events after trastuzumab treatment in patients with different antineoplastic drug application history among the 4 groups(all P﹥0. 05). Except for 2 patients with grade 2 sinus tachycardia whose heart rate returned to normal after treatment with beta﹣blocker,the other 63 patients did not need medical intervention. Conclusion The incidence of cardiac adverse events of trastuzumab treatment in patients with HER2﹣positive tumors was higher,but the severity of most of them were grade 1,which rarely cause serious cardiac functional or structural damage.

AIM:To determine circular RNA (circRNA) profiles in the diabetic mouse myocardium , and to investigate the effect of circRNA_000203 on fibrotic phenotypes in cardiac fibroblasts .METHODS:Masson trichrome stai-ning was performed on the myocardium of the diabetic db /db mice and the non diabetic db/m control mice .circRNA ex-pression profile in the diabetic myocardium was detected by circRNAs microarray .The expression of circRNA_000203 was determined by real time fluorescence quantitative PCR ( RT-qPCR ) .Recombinant circRNA_000203 adenovirus was pre-pared for enforced the expression of circRNA_000203 in mouse cardiac fibroblasts.The expression of Col1a2, Col3a1andα-SMA was determined in circRNA_000203-modified cardiac fibroblasts , respectively .RESULTS:Masson trichrome stai-ning showed that fibrosis was increased in the diabetic mouse myocardium .The results of circRNA array detection revealed that circRNAs were dysregulated in the diabetic myocardium .circRNA_000203 was up-regulated in the diabetic myocardi-um.Significant over-expression of circRNA_000203 was achieved in the cardiac fibroblasts after infection with the recombi-nant circRNA_000203 adenovirus.The mRNA and protein expression of Col1a2, Col3a1 and α-SMA was significantly in-creased in the cardiac fibroblasts with over-expression of circRNA_000203.CONCLUSION:circRNA_000203 is up-regu-lated in the diabetic mouse myocardium .It has pro-fibrotic effect on the cardiac fibroblasts .

AIM:To investigate the effect of microRNA-214 ( miR-214) on cardiomyocyte hypertrophy and the expression of the potential target genes .METHODS:A cell model of hypertrophy was established based on angiotensin-Ⅱ( Ang-Ⅱ)-induced neonatal mouse ventricular cardiomyocytes ( NMVCs) .Dual luciferase reporter assay was performed to verify the interaction between miR-214 and the 3’ UTR of MEF2C.The expression of MEF2C and hypertrophy-related genes at mRNA and protein levels was determined by RT-qPCR and Western blot , respectively .RESULTS:The expression of ANP, ACTA1,β-MHC and miR-214 was markedly increased in Ang-Ⅱ-induced hypertrophic cardiomyocytes .Dual lu-ciferase reporter assay revealed that miR-214 interacted with the 3’ UTR of MEF2C, and miR-214 was verified to inhibit MEF2C expression at the transcriptional level .The protein expression of MEF2C was markedly increased in the hypertro-phic cardiomyocytes .Moreover, miR-214 mimic, in parallel to MEF2C siRNA, inhibited the expression of hypertrophy-re-lated genes in Ang-Ⅱ-induced NMVCs.CONCLUSION:MEF2C is a target gene of miR-214, which mediates the effect of miR-214 on attenuating cardiomyocyte hypertrophy .

Background and objectiveIncidence and mortality rates of lung cancer are rising sharply. Small cell lung cancer patients prefer chemotherapy than surgery because of the insigniifcant side effects of Chinese medicine. Studies have shown that solasonine possesses an anti-tumor property. hTe aim of this study is to investigate the effect of solasonine on the apoptosis of lung cancer cell line H446.MethodsAppropriate concentration and time were selected with a CCK8 kit. hTe drug that was used in H446 cells was divided into four different concentrations: 0 μmol/L, 3.4 μmol/L, 6.8 μmol/L and 13.6 μmol/L. hTe changes in forms and nucleus of H446 cells that were stained with DAPI were observed under an inverted optical microscope. hTe effects on H446 cell apoptosis were detected by FCM. hTe changes in apoptosis-related proteins BCL2, BAX, and CASP3 were investigated using Western blot for 24 h.Results Solasonine reduced the survival ratio of H446 cells and in-hibited the proliferation with a dose-related effect. hTe survival ratio of H446 cells could be reduced to 16.77% (P<0.001), and the highest apoptosis ratio was 44.62% (P<0.001). Apoptosis was observed in H446 cells. Moreover, Western blot showed that the apoptosis-related proteins BAX and CASP3 were upregulated (P<0.05).ConclusionhTe proliferation of H446 cells can be inhibited by solasonine, and the expression of pro-apoptotic proteins is up-regulated, and the expression of anti-apoptotic proteins is down-regulated, thereby promoting the apoptosis of cells.