Objective To explore the clinical efficacy of rabeprazole combined with mosapride in the treatment of reflux esophagitis.MethodsThe clinical data of 315 patients with reflux esophagitis from December 2015 to December 2016 in our hospital were retrospectively analyzed, were randomly divided into two groups according to the time of admission.The control group (157 cases)was treated with rabeprazole, the observation group (158 cases) given rabeprazole combined with mosapride treatment.The clinical symptom scores before and after treatment, the effective rate of treatment, the quality of life before and one month after treatment and three months after treatment of two groups were compared.ResultsAfter treatment,the symptoms scores of the two groups were significantly lower than those before treatment, but the the scores in the observation group were significantly lower than those in the control group (P<0.05);The total effective rate was 96.2% in the observation group, which was significantly higher than that in the control group (79.0%), the difference between the two groups was statistically significant (P<0.05);The quality of life scores of the two groups were significantly higher than that before treatment, but the scores of one months after treatment and three months after treatment in observation group were significantly higher than those in control group (P<0.05).ConclusionReflux esophagitis with rabeprazole combined with mosapride treatment is significant,can better improve the clinical symptoms of patients, improve the treatment efficiency, and improve the quality of life of patients.

Objective To observe the vaccination reactions and immunogenicity of the application of lyophilized Vero cell rabies vaccine without adjuvant in a way of low-dose intradermal injection for post-exposure group. Methods Conducting post-exposure immunization for 256 persons with the class Ⅱ level exposure to rabies. Based on a randomized, single-blind principle, all subjects were divided into intradermal injection (ID) group (n= 128),injected 0.1 ml for each site in accordance with 0,3,7,28,90 d,2 sites,2 sites,2sites,1 site,1 site respectively, and intramuscular injection(IM) group(n= 128) in accordance with 0,3,7,14,28 d in full-volume (0.5ml) PVRV Deltoid injection. The local and systemic vaccination reactions were observed for the different injection ways. The indirect sandwich ELISA assay was used to analyze the antibody levels. Results For the intradermal injection group, the incidence rates for local redness and swelling, induration, pain, itch were 1.27%, 0.29% ,0.49% ,11.43% respectively,for the intramuscular group, the incidence rates were 1.09% ,0. 16% ,2. 81% ,1.41% respectively. From the point of systemic reactions,the incidence rates of fever,rash,headache,fatigue and weakness were 0.31 % ,0. 16% ,0. 31 % , 1.09% respectively in the intradermal injection group,and the rates were 0.31% ,0.31% ,0.63% , 1.09% respectively in intramuscular group. All the adverse effects often occurred following the 1st,2nd injection. The seroconversion rates for intradermal injection and intramuscular were 94.53% ,95.31% following 14 d immunization respectively,the rates were 96. 83% ,97.64% following 42 d immunization respectively. For the post-exposure group,no statistical difference in significance was found between the two seroconversion rates. Conclusion For the application of domestic lyophilized Vero cell rabies vaccine,its adverse reactions are mild,and immunogenicity is good.

Objectives:To assess the effectiveness and safety of ivabradine for the treatment of chronic heart failure in the context of the new quadruple combination. Methods:Clinical data of 656 chronic heart failure patients hospitalized in Nanjing Drum Tower Hospital from March 2021 to June 2022 were retrospectively collected,and the patients were divided into control group(n=361)and observation group(n=295)according to ivabradine use,and both groups were treated with the new quadruple drug therapy.Propensity score matching was performed,268 patients in the observation group and 268 patients in the control group were successfully matched.The effectiveness(primary endpoint was the composite endpoint of cardiovascular death and rehospitalisation for worsening heart failure within 1 year of discharge;secondary endpoints were rehospitalisation for worsening heart failure,all-cause rehospitalisation,cardiovascular death,and all-cause death)and safety outcome measures(including bradycardia,atrial fibrillation,blurred vision,renal impairment,and hypertension)were compared between the two groups at 1 year after treatment. Results:After matching,there were no statistically significant differences at baseline characteristics between the two groups.Kaplan-Meier survival curve showed that the occurrence rates of primary endpoints(P=0.031),readmission for worsening heart failure(P=0.020),and all-cause readmission(P=0.036)were lower in the observation group than in the control group.Multivariate Cox proportional hazard regression analysis showed that the occurrence rates of primary endpoint events(P=0.045)and readmission for heart failure worsening(P=0.028)were lower in the observation group than in the control group. Conclusions:The ivabradine use on top of the new quadruple therapy regimen in patients with chronic heart failure is beneficial to improve one-year prognosis with favorable safety profile.

Objective To construct a carbon dioxide(CO2)laser-induced corneal injury model in mice and observe the process of corneal wound healing.Methods Twenty eyes of ten C57BL/6J mice were divided into 4 groups.The cen-tral corneas in each group were irradiated by CO2 laser with a wavelength of 10.6 μm,spot diameter of 2 mm and power of 0.94 W.The exposure doses were 3.0 J·cm-2,4.5 J·cm-2,7.5 J·cm-2 and 10.5 J·cm-2,with corresponding expo-sure durations of 0.10 s,0.15 s,0.25 s and 0.35 s.Corneal injury severity was assessed using a slit lamp microscope,opti-cal coherence tomography and histopathological evaluation at 1 day after the exposure to determine the proper exposure dose for constructing a corneal injury model.Subsequently,the corneal injury model was constructed and the same meth-ods were used to monitor wound healing before,and 0 hours to 6 months after the exposure.Results No obvious corne-al injury was observed at an exposure dose of 3.0 J·cm-2.At an exposure dose of 4.5 J·cm-2,an off-white injury area appeared on the central cornea with loss of epithelium and endothelium.At an exposure dose of 7.5 J·cm-2 or 10.5 J·cm-2,the injury area became porcelain white,the cornea was thickened,and the iris was seen adhering to the margin of the cornea.Therefore,4.5 J·cm-2 CO2 laser was selected to construct a corneal injury model.At this exposure dose,the cornea swelled and thickened rapidly after injury,reached the maximum thickness 1 day after the exposure,and then grad-ually recovered,returning to normal by 14 days after the exposure.In the early stage(0 hours to 3 days after the expo-sure),the cornea showed shedding of injured epithelium and endothelium,migration of new epithelium and endothelium,and infiltration and regression of inflammatory cells.At the late stage(7 days to 6 months after the exposure),the cornea gradually returned to a normal physiological state,but some of the injured cornea exhibited stromal hyperplasia.Conclu-sion A CO2 laser with an exposure dose of 4.5 J·cm-2 can be used to construct a corneal injury model in mice.The a-cute phase of corneal injury primarily occurs within 3 days after the exposure.The cornea tends to restore its original physi-ological structure,but the corneal transparency cannot return to a normal state.

Objective To explore the corneal wound healing mechanism after 3.74 μm infrared laser irradiation.Methods Twenty-seven C57BL/6J mice(six to eight weeks old)were randomly divided into a normal group(3 mice)and an experimental group(24 mice).Mice in the normal group were not subjected to any treatment.The corneas of mice in the experimental group were damaged by infrared laser at a wavelength of 3.74 μm.The spot diameter was 2 mm,the exposure duration 0.8 s,and the radiant exposure 23.2 J·cm-2.Pathological sectioning of corneas was performed at 3 h,6 h,12 h,1 d,3 d,7 d,14 d,and 21 d after laser irradiation in the experimental group,with 3 mice at each time point.It was the same for mice in the normal group.Immunohistochemical staining was conducted to examine neutrophil elastase,CD68,CD163 and thrombomodulin-positive cells and identify neovascularization.Results Neutrophil elastase,CD68,CD163,and thrombomodulin-positive cells were not detected in the corneal stroma of mice in the normal group.Neutrophil elastase-positive cells were detected in the damaged corneal periphery of mice in the experimental group at 3 h,migrated to the damaged area at 12 h,peaked at 1 d,and then decreased gradually with time,but still existed slightly at 21 d after laser irradiation.CD68-positive cells were detected in the damaged corneal periphery of mice in the experimental group at 12 h and in the damaged area at 1 d through 21 d after laser irradiation.CD163-positive cells were found in the damaged corneal periphery of mice in the experimental group at 7 d and in the damaged area at 14 d and 21 d after laser irradiation.Throm-bomodulin-positive cells were found in the damaged area of the corneal stroma at 14 d and 21 d after laser irradiation.Con-clusion During the wound healing process after 3.74 μm infrared laser-induced full-thickness corneal injury in mice,a large number of inflammatory cells migrate from the damaged corneal periphery or limbus to the damaged area.Neutrophils and M1 macrophages infiltrate in the early stage,while M2 macrophages are involved in the later stage,accompanied by neovascularization.

OBJECTIVE To evaluate the cost-effectiveness of ivabradine in the treatment of chronic heart failure （CHF） in the context of “Quadruple Therapy” from the perspective of the health system. METHODS Based on real-world cohort data， the Markov model was constructed according to the natural progression of CHF， with a cycle time of 3 months， a study timeframe of 20 years， and a discount rate of 5%. Using quality-adjusted life year （QALY） and incremental cost-effectiveness ratios （ICER） as the output indexes， the cost-utility analysis was used to evaluate the cost-effectiveness of ivabradine in combination with the “Quadruple Therapy” regimen， compared with the “Quadruple Therapy” regimen for the treatment of CHF， and the robustness of the results of the base analysis was verified by univariate sensitivity analysis and probabilistic sensitivity analysis. RESULTS The results of the base analysis showed that the ICER of ivabradine combined with the “Quadruple Therapy” regimen was 165 065.54 yuan/QALY， compared with the “Quadruple Therapy” regimen， which was lower than the willingness-to-pay （WTP） threshold （257 094 yuan/QALY） based on 3 times of China’s gross domestic product （GDP） per capita in 2022. The results of the univariate sensitivity analysis showed that the discount rate had the greatest impact on the robustness of the model. The probabilistic sensitivity analysis showed that the probability that the ivabradine combined with the “Quadruple Therapy” regimen was cost-effective under the WTP threshold in this study was 59.50%. CONCLUSIONS When using 3 times China’s 2022 GDP per capita （257 094 yuan/ QALY） as the WTP threshold， the combination of ivabradine and the “Quadruple Therapy” regimen for treating CHF is cost- effective.

OBJECTIVE To evaluate the effects of ivabradine on vascular endothelial function in patients with coronary artery disease. METHODS PubMed， Embase， the Cochrane Library， Web of Science， CNKI， Wanfang Data， VIP and CBM databases were retrieved to collect randomized controlled trials （RCTs） about ivabradine （intervention group） versus placebo or β-blocker （control group） from the inception to Mar. 20th 2023. The meta-analysis was performed by using RevMan 5.4 software after literature screening， data extraction and quality evaluation. RESULTS A total of 12 RCTs were included， involving 1 206 patients. The results of meta-analysis showed that the levels of flow-mediated dilation （FMD） [MD＝1.71， 95%CI （0.96， 2.46）， P＜0.000 01] and nitric oxide （NO） [MD＝5.80， 95%CI （5.02， 6.59）， P＜0.000 01] in the intervention group were significantly higher than control group， while endothelin-1（ET-1） level was significantly lower than control group [MD＝－7.45， 95%CI （－8.42， －6.47）， P＜0.000 01]. There was no statistical significance in nitroglycerin-mediated dilation （NMD） level between 2 groups [MD＝0.13， 95%CI（－0.74， 1.00）， P＝0.77]. Subgroup analyses based on the different medications and intervention time in the control group showed better improvement in FMD level of patients receiving ivabradine， compared with placebo （P＜0.05）； compared with placebo and β-blocker， the level of NO in patients receiving ivabradine was improved significantly （P＜0.05）， while ET-1 level was decreased significantly （P＜0.05）. Regardless of the duration of the intervention， the levels of FMD， NO， and ET-1 in the intervention group were significantly improved compared to the control group （P＜0.01）， while the difference in NMD was not statistically significant （P＞0.05）. CONCLUSIONS Ivabradine can improve vascular endothelial function in patients with coronary artery disease.

OBJECTIVE To evaluate the clinical effectiveness and safety of domestic generic and imported original clopidogrel for antiplatelet therapy in patients with acute coronary syndrome （ACS）. METHODS The clinical data of ACS patients in Nanjing Drum Tower Hospital of China Pharmaceutical University from January 2020 to June 2021 were retrospectively collected by using electronic medical record system， and the patients were divided into original drug group （321 cases） and generic drug group （328 cases） according to the drug use. Both groups were given dual antiplatelet therapy with clopidogrel and aspirin. The effectiveness and safety outcomes of the two groups were followed up for 12 months and compared， the related influential factors were analyzed. RESULTS Major adverse cardiovascular events （MACE） occurred in 16 and 22 patients in original drug group and generic drug group respectively， including nonfatal myocardial infarction （4 and 5 cases）， stroke （2 and 4 cases）， revascularization （8 and 3 cases）， cardiovascular related death （2 and 4 cases）， and all-cause death （4 and 6 cases）. There were 12 and 7 patients with major bleeding events， 38 and 29 patients with minor bleeding events， and 33 and 21 patients with non-bleeding adverse events. There was no statistically significant difference in the cumulative incidence of related events （P values of Log-Rank tests were all greater than 0.05）. Cox regression analysis showed that the use of generic clopidogrel did not increase the risk of MACE and major bleeding events in ACS patients [hazard ratio of 1.305 and 0.416， 95% confidence interval of （0.678， 2.512） and （0.155， 1.117）， respectively， P＞0.05]， and the combination of proton pump inhibitors （PPI） could reduce the risk of major bleeding events [hazard ratio of 0.196， 95% confidence interval of （0.063， 0.611）， P＜0.05]. CONCLUSIONS Compared with imported original drug， domestic generic clopidogrel has similar clinical effectiveness and good safety. Combined use of PPI may be a beneficial factor to reduce the occurrence of major bleeding events in patients.