OBJECTIVE To comprehensively evaluate the efficacy， safety and cost-effectiveness of insulin icodec in treating type 2 diabetes mellitus （T2DM）， providing evidence-based guidance for new drug selection in hospital and clinical medication decision-making. METHODS PubMed， Cochrane Library， Embase， CNKI， Wanfang， VIP and foreign health technology assessment （HTA） websites were searched by using rapid health technology assessment from inception to 15 July 2025 for systematic reviews/meta-analyses， pharmacoeconomic studies， and HTA reports on insulin icodec in the treatment of T2DM. After data extraction and quality assessment， the findings of the included studies were analyzed descriptively. RESULTS Ten systematic reviews/meta-analyses and three pharmacoeconomic studies were included. Among them， 4 systematic reviews/meta-analyses were of high quality； the overall quality of the 3 pharmacoeconomic studies was relatively good. Regarding efficacy， insulin icodec was superior to once-daily basal insulin in reducing glycated hemoglobin （HbA1c） and in achieving the target of HbA1c＜7% （P＜0.05）. No significant differences were observed between icodec insulin and comparators in lowering fasting plasma glucose （P＞0.05）. For safety， insulin icodec did not increase the incidence of any adverse events （AEs）， serious AEs， clinically significant hypoglycemia （random glucose＜3 mmol/L）， injection-site reactions， or allergic reactions， compared with once-daily basal insulin overall （P＞ 0.05）； however， insulin icodec was associated with a significant increase in body weight （P＜0.05）. Domestic economic evaluations indicated that insulin icodec was more cost-effective than insulin glargine and insulin degludec when its annual costs were in the range of 784.90-1 145.96 and 597.66-736.34 US dollars， respectively. CONCLUSIONS Insulin icodec demonstrates favorable efficacy and safety profiles in the treatment of T2DM； however， attention should be paid to the risk of weight gain. Under China’s healthcare system， insulin icodec demonstrates greater economic value only when the patient’s weekly required basal insulin dose falls within a specific range，and clinical practice requires individualization.

Objective To analyze the correlation between lesion volume,lesion mass,and maximum lesion diameter in the assessment of advanced hepatocarcinoma with lung metastasis,and to evaluate the application value of total volume response and total mass response of lung metastatic lesions in efficacy assessment.Methods A retrospective analysis was conducted on the CT imaging data of 20 patients clinically confirmed with hepatocarcinoma and lung metastases,followed by subsequent follow-up to monitor their survival outcomes.Volume measurement software was used to measure the volume of lesions before and after treatment.We recored lesion diameter,volume measurements and CT values,calculated the mass of the lesions.The correlation between lesion volume,mass and diameter was analyzed,as well as the correlation between the change rates of volume,mass and lesion diameter.Additionally,the total volume and total mass of all lesions were calculated.The correlation between the change rates of total volume/total mass and the change rate of pulmonary lesion diameter under the RECIST 1.1 criteria,as well as the correlation with changes in patients'tumor markers,were analyzed.Furthermore,the overall volume response and overall mass response of lesions were evaluated based on changes in total volume and total mass,and their consistencies with the RECIST 1.1 criteria for efficacy evaluation were analyzed.Finally,univariate Cox regression analysis was performed to explore the association between these variables and patient survival outcomes.Results There was strong correlation between lesion volume,mass and tumor diameter(r=0.771,0.775),between the rate of change in mass and the rate of change in lesion diameter(r=0.846),and between the rates of change in total volume/total mass and the rate of change in pulmonary lesion diameter under the RECIST 1.1 criteria(r=0.800,0.896).The correlation between the rates of change in total volume/total mass and patients'tumor markers was not statistically significant.There was moderate correlation between the rate of change in volume and the rate of change in lesion diameter(r=0.692).The evaluation results of total volume response and total mass response for pulmonary lesions in advanced hepatocarcinoma with lung metastasis were generally consistent with the RECIST 1.1 criteria(Kappa=0.486,0.426).Univariate Cox regression analysis revealed that total lesion volume(P=0.047)and total lesion mass(P=0.049)were independent prognostic factors for survival outcomes.Conclusion Lesion volume,mass,and diameter,as well as their respective change rates,were found to be interrelated.Furthermore,total lesion volume and total lesion mass were identified as independent prognostic factors for survival outcomes.The total volume response and total mass response are promising evaluation methods in evaluating the efficacy of lung metastasis of hepatocarcinoma,which are different from the RECIST 1.1 evaluation criteria.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Objectives:To investigate the predictive value of Murray's law-based quantitative flow ratio(μQFR)in side branches for long-term clinical prognosis in patients with non-left main bifurcation lesions who underwent simple main branch stenting,and to provide a potential functional assessment standard for intervention decision-making on coronary bifurcation lesions.Methods:A retrospective analysis was conducted in 408 patients with non-left main bifurcation lesions who underwent simple main branch stenting at Lianyungang First People's Hospital and Nanjing First Hospital between July 2018 and January 2021.The study utilized third-generation QFR software to analyze pre-and post-procedure anatomical and functional parameters of the target lesion's main branch and key branches.The primary endpoint was target vessel failure(TVF)events during the 3-year follow-up.Patients were stratified into TVF and non-TVF groups.Baseline characteristics,procedural data,and pre-/post-procedural parameters of target vessels were compared between groups.Multivariable Cox regression was performed to identify predictors of TVF.Diagnostic efficacy of predictors was evaluated using area under the receiver operating characteristic(ROC)curve(AUC)with DeLong's method for comparison.Patients were dichotomized based on the optimal cutoffof post-procedural side branch μQFR,with TVF incidence rates compared via Cox regression and Kaplan-Meier analysis.Results:During 3-year follow-up,54 patients(13.2%)experienced TVF(TVF group),data were compared with 354 patients(86.76%)without TVF(non-TVF group).The TVF group showed higher post-procedural side branch diameter stenosis([32.93±17.80]%vs.[22.62±11.96]%,P<0.001)and lower μQFR(0.80±0.10 vs.0.89±0.07,P<0.001).Multivariate Cox regression identified higher post-procedural side branch μQFR as an independent protective factor against 3-year TVF(per 0.01 increase:HR=0.903,95%CI:0.850-0.959,P<0.001).ROC curves indicated that post-procedural side branch μQFR had moderate diagnostic efficacy for predicting 3-year TVF(AUC=0.769,95%CI:0.678-0.861,P<0.001),with a significantly higher AUC value than post-operative side branch area stenosis and minimal lumen diameter(both P<0.001),the optimal cutoffvalue was 0.84.Multivariate Cox regression and Kaplan-Meier survival analysis revealed markedly higher 3-year TVF rates in patients with μQFR≤0.84 compared to patients with μQFR>0.84(HR=4.007,95%CI:2.342-6.855,P<0.001;28.3%vs.7.9%,log-rank P<0.001).Conclusions:For patients with bifurcation lesions not involving the left main,the immediate post-procedural side branch μQFR could better predict 3-year TVF than anatomical indices.Maintaining post-stenting side branch μQFR>0.84 may optimize clinical outcomes when using a single-stent strategy.

Objective:To explore the application effect of BOPPPS teaching model in the teaching of Food Safety Supervision and Management course.Methods:Students of two parallel classes majoring in the Food Quality and Safety of the same grade of a university in Liaoning Province were selected,and the traditional teaching model and BOPPPS teaching model were used for teaching practice respectively.The scores,teaching effect and satisfaction of two groups were compared.Results:The regular performance and total scores of the experimental group were significantly higher than those of the control group(P＜0.05).In terms of enhancing students'interest in food safety supervision,improving knowledge and skills,cultivating self-directed learning and teamwork abilities,strengthening the close connection between the course and real cases,and providing assistance for future career,the experimental group performed significantly better than the control group(P＜0.05).Moreover,the satisfaction of the experimental group was higher than that of the control group(P＜0.05).Conclusion:BOPPPS teaching model has a remarkable effect in the teaching of Food Safety Supervision and Management course,providing an effective approach for the teaching reform of this course.

Aim To investigate the predictive value of the Murray law-based quantitative flow ratio(μQFR)after target vessel pretreatment for vascular-related adverse events in patients with de novo coronary lesions treated with drug-coated balloon.Methods This retrospective study included 223 lesions from 223 patients who underwent drug-coated balloon-only strategy and completed 2-year clinical follow-up.Coronary angiographic images of target vessels pre-procedure,post-balloon and post-procedure were collected,and analyzed using a novel Murray's law-based algorithm.The μQFR analysis of each target vessel included not only the μQFR value of the target vessel,but also the length of the target vessel,the degree of vessel diameter stenosis,the reference lumen diameter,the minimum lumen diameter and blood flow velocity.The primary endpoint was defined as the postoperative vessel-oriented composite endpoint(VOCE).Results During the2-year clinical follow-up period,a total of 25 patients(11.2%)experienced VOCE events.Com-pared with the control group,patients with VOCE events after pretreatment showed a decrease in μQFR(P<0.001).Multivariate Logistic analysis showed that a lower target vessel μQFR after pretreatment(OR=0.931,95%CI:0.894～0.969,P<0.001)was an independent predictor of VOCE events.ROC curve analysis showed that the cut-off value for predicting 2-year VOCE events using preprocessed μQFR was 0.83(95%CI:0.727～0.840),with a sensitivity of 72.7%and a specificity of 84.0%(AUC=0.773,95%CI:0.676～0.870,P<0.001).Survival analysis showed that compared with patients with μQFR>0.83,patients with μQFR≤0.83 had a significantly higher incidence of VOCE events at 1 and 2 years,increasing to 3.909 times(16.9%vs.4.6%,HR=3.909,95%CI:1.539～9.930,P=0.004)and 2.867 times(19.7%vs.7.2%,HR=2.867,95%CI:1.301～6.316,P=0.009).After adjusting for potential con-founds,patients with pretreated μQFR≤0.83 had a 2.567 times in 2-year incidence of VOCE events(HR=2.567,95%CI:1.151～5.727,P=0.021)and a 3.712 times in 1-year incidence of VOCE events(HR=3.712,95%CI:1.478～9.810,P=0.006)compared to patients with good pretreatment.Conclusions For patients with in situ coronary artery disease,a lower μQFR after pretreatment increases the risk of postoperative adverse clinical events.μQFR≤0.83 may be used to evaluate the effectiveness of lesion pretreatment.

Objective:To analyze the epidemiological characteristics and infection sources of cholera in China from 2005 to 2024.Methods:A total of 2 066 cholera cases were included in the study, which were obtained from the China Disease Control and Prevention Information System (CDPCIS) of China CDC. The information on cholera clusters was downloaded from the National Public Health Emergency Event Surveillance System (PHEESS) of China CDC. A total of 128 cholera clusters were included and analyzed in this study. The epidemiological characteristics and infection sources of cholera were analyzed. The Jointpoint model was applied to analyze the incidence trend, and annual percentage change (APC) was also quantified.Results:From 2005 to 2024, a total of 2 066 cholera cases were reported, with an average of 103 cases reported annually. Specifically, the incidence showed a marked downward trend from 2004 to 2015 ( APC=-26.78%, P=0.006). During 2015-2024, the disease remained at low endemic levels, with an average of 18 reported cases annually ( APC=-2.68%, P=0.807). Cholera peak season was from May to October. A total of 24 provinces reported cholera cases, which were mainly distributed in Zhejiang, Fujian, Beijing, Jiangsu, Anhui, Guangdong, and Hainan provinces, accounting for 78.03% of the total cases. Pathogen surveillance indicated an alternating prevalence of Vibrio cholerae serogroups O1 and O139 among laboratory-confirmed cases between 2005 and 2024. There was a disparity in the dominant serogroup of Vibrio cholerae by region. The results from 128 cholera clusters indicated that cholera outbreaks frequently occurred in rural banquets (64.84%), followed by regular restaurants (13.28%). Among these, 63 clusters (49.22%) with identified infection sources indicated that foodborne transmission (95.24%) was the primary mode of cholera transmission, which mainly through seafood and aquatic products, such as soft-shelled turtles, shrimp and shellfish. The characteristics of cholera clusters caused by Vibrio cholerae serogroups O1 and O139 showed statistically significant differences in scale, attack rate, place of residence, setting, and infection source ( P<0.05). Conclusion:Cholera incidence has remained consistently low since 2015 in China, mainly in sporadic cases. Rural gatherings (e.g., wedding banquets) are the main settings for cholera clusters. The main infection sources are predominantly caused by cross-contamination due to improper processing practices of aquatic products, such as soft-shelled turtles.

OBJECTIVE To investigate the in vitro activity of Chansu injection against SARS-CoV-2 infection and determine whether bufalin is the primary active component responsible for its efficacy.METHODS The half-maximal effective concentration(EC50)of Chansu injection and bufalin against SARS-CoV-2 infection was determined using the CellTiter-Glo cell viability assay.qPCR was performed to assess the effects of Chansu injection and bufalin on mRNA levels of SARS-CoV-2 NP protein,inflammatory factors,and interferons in virus-infected cells.A cell-cell membrane fusion model was established,and the impact of the drugs on membrane fusion between HEK-293T and HEK-293T-ACE2 cells was evaluated using a luciferase reporter gene assay.RESULTS Chansu injection exhibited anti-SARS-CoV-2 virus infection activity,with an EC50 of 85.56 ng·mL-1.Chansu injec-tion significantly reduced the mRNA levels of viral NP protein(P<0.05),IFN-λ2/3(P<0.05),ISG-15 and RIG-I(P<0.000 1)in SARS-CoV-2 infected Calu-3 cells,and the mRNA levels of inflammatory factors IL-6 and TNF-α were significantly reduced(P<0.000 1).The EC50 of bufalin in inhibiting SARS-CoV-2 virus-infected cells was 13.3 nmol·L-1,which might be the main active component of Chansu injection in resisting SARS-CoV-2 virus-infected cells.Chansu injection could significantly inhibit the cell membrane fusion mediated by the S protein of SARS-CoV-2 virus,thereby blocking the virus invasion.CONCLUSION Chansu injection demonstrates in vitro anti-SARS-CoV-2 activity by suppressing NP protein expression,reducing inflammatory cytokine lev-els,and blocking viral entry through membrane fusion inhibition.Bufalin is likely the key active component responsible for its anti-SARS-CoV-2 effects.

BACKGROUND:Psoralen has a strong anti-osteoporotic activity and may have a restorative effect on chemotherapy-induced osteoporosis. OBJECTIVE:To explore the restorative effect of psoralen on the osteogenic differentiation of bone marrow mesenchymal stem cells in mice inhibited by cyclophosphamide and its mechanism. METHODS:C57BL/6 mouse bone marrow mesenchymal stem cells were isolated and cultured.Effect of psoralen on viability of bone marrow mesenchymal stem cells was detected by MTT assay.Osteogenic induction combined with alkaline phosphatase staining was used to determine the optimal dose of psoralen to restore the osteogenic differentiation of bone marrow mesenchymal stem cells inhibited by cyclophosphamide.The mRNA expression levels of Runx2,alkaline phosphatase,Osteocalcin,osteoprotegerin,and Wnt/β-catenin signaling pathway-related genes Wnt1,Wnt4,Wnt10b,β-catenin,and c-MYC were measured by RT-qPCR at different time points under the intervention with psoralen.The protein expression of osteogenic specific transcription factor Runx2 and Wnt/β-catenin signaling pathway related genes Active β-catenin,DKK1,c-MYC,and Cyclin D1 was determined by western blot assay at different time points under the intervention with psoralen. RESULTS AND CONCLUSION:(1)There was no significant effect of different concentrations of psoralen on the viability of bone marrow mesenchymal stem cells.The best recovery of the inhibition of osteogenic differentiation of bone marrow mesenchymal stem cells caused by cyclophosphamide was under the intervention of psoralen at a concentration of 200 μmol/L.(2)Psoralen reversed the reduction in osteogenic differentiation marker genes Runx2,alkaline phosphatase,Osteocalcin and osteoprotegerin mRNA expression and Runx2 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(3)Psoralen reversed the decrease in Wnt/β-catenin pathway-related genes Wnt4,β-catenin,c-MYC mRNA and Active β-catenin,c-MYC,and Cyclin D1 protein expression and the increase in DKK1 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(4)The results showed that cyclophosphamide inhibited osteogenic differentiation of bone marrow mesenchymal stem cells in mice,and psoralen had a restorative effect on it.The best intervention effect was achieved at a concentration of 200 μmol/L psoralen,and this protective effect might be related to the activation of Wnt4/β-catenin signaling pathway by psoralen.

According to the principle and current domestic and international construction processes of core outcome set(COS) and the characteristics of post-stroke aphasia, this study built COS with evidence-based support for traditional Chinese medicine(TCM) treatment of post-stroke aphasia. Firstly, a comprehensive review was conducted on the articles about the TCM treatment of post-stroke aphasia that were published in the four major Chinese databases, three major English databases, and three clinical registration centers over the past five years. The articles were analyzed and summarized, on the basis of which the main part of the COS for clinical research on the TCM treatment of post-stroke aphasia was formed. Secondly, clinical doctors and related nursing personnel were interviewed, and important outcome indicators in the clinical diagnosis and treatment process were supplemented to form a pool of core outcome indicators. Two rounds of Delphi surveys were carried out to score the importance of the core outcome indicators in the pool. Finally, a consensus meeting of experts was held to establish the COS for clinical research on the TCM treatment of post-stroke aphasia. The final COS included a total of 268 studies [236 randomized controlled trials(RCTs), 21 Meta-analysis, and 11 clinical registration protocols] and 20 open questionnaire survey results. After two rounds of Delphi surveys, a total of 14 outcome indicators and their corresponding measurement tools were included in the expert consensus meeting. The final expert consensus meeting determined the COS for post-stroke aphasia, which included 9 indicator domains and 12 outcome indicators.
Humans ; Aphasia/therapy* ; Stroke/complications* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Treatment Outcome