BACKGROUND:Wogonin is a flavonoid extracted from the root of Scutellaria baicalensis.Previous studies have shown that baicalein has protective effects against cerebral ischemia-reperfusion injury,and can also reduce blood sugar and complications in diabetic mice,but its role and mechanism in diabetic cerebral infarction remain unclear. OBJECTIVE:To explore the effect of wogonin on nerve injury in rats with diabetic cerebral infarction and its mechanism. METHODS:Sprague-Dawley rats were randomly divided into six groups:control group,model group,low-dose wogonin group,medium-dose wogonin group,high-dose wogonin group,and high-dose wogonin+Ras homolog gene family member A(RhoA)activator group.Except for the control group,the other rats were established with diabetes and cerebral ischemia models using intraperitoneal injection of streptozotocin and middle cerebral artery occlusion.Low,medium-and high-dose wogonin groups were intragastrically given 10,20,40 mg/kg wogonin,respectively;high-dose wogonin+RhoA activator group was intragastrically given 40 mg/kg wogonin and intraperitoneally injected 10 mg/kg lysophosphatidic acid;control group and model group were given the same amount of normal saline once a day for 7 consecutive days.Rats in each group were evaluated for neurological deficits and their blood glucose levels were measured after the last dose.TTC staining was applied to detect the volume of cerebral infarction.Hematoxylin-eosin staining was applied to observe pathological changes in brain tissue.ELISA kit was applied to detect tumor necrosis factor-α,interleukin-6,malondialdehyde,and superoxide dismutase levels in brain tissue.Western blot was applied to detect the protein expression of RhoA and Rho-associated protein kinase(ROCK)2 in brain tissue. RESULTS AND CONCLUSION:Compared with the control group,the neuronal structure of rats in the model group was severely damaged,with cell necrosis and degeneration,the neurological deficit score,blood glucose level,and infarct volume were significantly elevated(P<0.05),the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue were significantly increased(P<0.05),and the superoxide dismutase level was decreased(P<0.05).Compared with the model group,the low-,medium-,and high-dose wogonin groups showed improved neuronal damage,reduced cell degeneration and necrosis,a significant reduction in neurological deficit score,blood glucose level,infarct volume,and the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue,and an increase in the superoxide dismutase level(P<0.05).Compared with the high-dose wogonin group,the high-dose wogonin+RhoA activator group significantly weakened the improvement in the above indexes of rats with diabetic cerebral infarction(P<0.05).To conclude,wogonin can improve the blood glucose level in rats with diabetic cerebral infarction,reduce cerebral infarction and nerve injury,and its mechanism may be related to the inhibition of RhoA/ROCK signaling pathway.

OBJECTIVE To systematically evaluate pharmacoeconomic studies on treatment strategies for transfusion- dependent β thalassemia （TDT） both in China and internationally， to inform clinical decision-making and health resource allocation， and provide methodological references for future domestic research in China. METHODS Databases including PubMed， Embase， Web of Science， the Cochrane Library， CNKI， Wanfang Data， and VIP were searched for pharmacoeconomic studies related to TDT treatments from inception to December 2024. Two researchers independently screened the literature， extracted data， and assessed risk of bias using the Consolidated Health Economic Evaluation Reporting Standards 2022 （CHEERS 2022） checklist. A qualitative systematic review was conducted focusing on model structure， costs， health outcomes， uncertainty analysis， and economic evaluation results. RESULTS A total of 1 685 articles were initially identified， and 13 pharmacoeconomic studies were ultimately included. The overall quality of the included studies was relatively high， covering interventions including blood transfusion and iron chelation therapy （BT-ICT）， hematopoietic stem cell transplantation （HSCT）， and gene therapy. All studies employed cost-utility analysis from societal， healthcare system， and payer perspectives. Markov models were most frequently used in model design. Most studies adopted a lifetime horizon with a cycle length of one year and a discount rate of 1.5% to 5%. Costs mainly focused on direct medical costs， sourced from national insurance databases and published literature. Utility values were primarily derived from literature or measured using techniques such as time trade-off. Most studies conducted both deterministic and probabilistic sensitivity analyses， identifying the costs of iron chelators and utility values as key influential parameters. Some studies also performed scenario analyses. CONCLUSIONS HSCT was likely more cost-effective than BT-ICT for pediatric/ adolescent patients. BT-ICT demonstrated superior cost-utility for adult patients， with the deferiprone regimen potentially being the most cost-effective option. Current domestic and international pharmacoeconomic evaluations for TDT remain limited. Future research should adopt a societal perspective， use a lifetime horizon， and strictly follow the CHEERS 2022 checklist when conducting pharmacoeconomic evaluations of treatments for TDT.

OBJECTIVE To explore the lipid-regulating mechanism of the classic prescription Zexie Decoction on hyperlipidemia model mice.METHODS ELISA method was used to detect the four blood lipid indexes,liver function indicators and cholesterol acyltransferase levels in serum.HE and Oil Red O staining were used to determine the pathology of liver tissue.Network pharmacology was used to predict the lipid-lowering related targets of Zexie Decoction,and the GO function and KEGG pathway enrichment analyses of the intersection targets were realized.PCR chip technology was used to detect the target genes for network pharmacology screening,and qPCR and Western blot were used to detect gene and protein expression levels.RESULTS Zexie Decoction significantly regula-ted the four blood lipid indexes in hyperlipidemia model mice,improved the increase in liver damage indicators caused by high lipids,and had a reverse regulatory effect on the key enzymes HMGR and CYP7A1 of lipid metabolism and the lipid transporters ABCA1 and Apo-A1 in liver tissue.HE and Oil Red O staining showed that Zexie Decoction improved the pathological morphology of liver tissue,reduced lipid deposition in liver tissue,and significantly decreased the positive area ratio(P<0.01).The PCR chip obtained 44 re-verse-regulated genes,GO functional enrichment analysis obtained 266 entries,and KEGG pathway enrichment analysis screened 99 signaling pathways.The results of qPCR and Western blot showed that Zexie Decoction significantly downregulated the expression of PIK3CG,AKT1,and IL-6 genes(P<0.05,P<0.01),upregulated the expression of ABCG1 gene(P<0.05),downregulated PI3Kinase p110β,p-AKT(Ser473)and SREBP-1c protein expression levels(P<0.01),and reversely regulated miR21-5p(P<0.01).CONCLUSION Zexie Decoction has a significant regulatory effect on lipid metabolism in hyperlipidemia model mice and can improve liver damage caused by hyperlipidemia.Its lipid-regulating effect may be related to regulating cholesterol metabolism and transport in the body,and is closely linked to the miR21/PI3K-Akt/SREBP pathway.The lipid-regulating effect of the whole formula of Zexie Decoction is better than that of a single herb.

Objective:To analyze the influencing factors of short-term efficacy of 125I seed implantation for recurrent cervical metastatic lymph nodes of esophageal squamous cell carcinoma after external beam radiation therapy (RESCC). Methods:From January 2013 to March 2019, 47 patients (42 males, 5 females; age: 47-77 years) with RESCC who underwent CT guided 125I seed implantation in Hebei General Hospital were retrospectively analyzed. Patients were divided into effective group (complete remission (CR)+ partial remission (PR)) and ineffective group (stable disease (SD)+ progressive disease (PD)) according to response evaluation criteria in solid tumors (RECIST) at 3 months after implantation. Multivariate logistic regression was used to analyze the independent influencing factors of short-term efficacy. Cut-off values were determined by ROC curve. Results:Of 47 patients, 26 were effective (3 were CR and 23 were PR) and 21 were ineffective (7 were SD, 14 were PD). Multivariate regression analysis showed that tumor diameter, immediate postoperative dose delivered to 90% gross tumor volume ( D90), recurrence interval time were independent influencing factors of short-term efficacy (odds ratio ( OR; 95% CI): 4.240(1.220-14.737), 0.999(0.999-1.000), 0.989(0.979-1.000), Wald values: 5.163, 5.043, 3.956, all P<0.05). ROC curve showed that the AUC of tumor diameter, D90 and recurrence interval time were 0.782, 0.786 and 0.838 respectively, with cut-off values of 4.85 cm, 115.78 Gy and 297.5 d respectively. Conclusions:The short-term efficacy of 125I seed implantation for RESCC is mainly related to the tumor diameter, immediate postoperative D90 and recurrence interval time. Patients with tumor diameter <4.85 cm, immediate postoperative D90>115.78 Gy and recurrence interval time >297.5 d have better efficacy.

OBJECTIVE To evaluate the econo mical efficiency of ensatinib i n the first-line treatment of anaplastic lymphoma kinase（ALK）positive-advanced non-small cell lung cancer （NSCLC），so as to provide reference for China ’s medical insurance decision-making and rational drug use in clinic. METHODS A three-state partitioned survival model was constructed from the perspective of China ’s health system ，based on the data of the international multi-center phase Ⅲ clinical trial （eXalt3 trail），with simulation time limit of 10 years，cycle period of 30 days. The economical efficiency of ensatinib was compared with that of crizotinib（standard treatment ）in the first-line treatment of ALK positive-advanced NSCLC. The incremental cost-effectiveness ratio （ICER） was calculated with quality-adjusted life years （QALYs） as utility index. The stability of basic analysis results was validated through uncertainty analysis. RESULTS The basic analysis results showed that compared with crizotinib group ， incremental cost per capita of ensatinib group was －343 370.36 yuan，incremental utility per capita was 0.76 QALYs，ICER was －454 292.25 yuan/QALY，which was far lower than the willingness-to-pay （WTP）threshold of 1 time of China ’s per capita gross domestic product （GDP，80 976 yuan）in 2021. The results of univariate sensitivity analysis showed that progression-free survival （PFS）status utility ，progression of disease （PD）status utility and subsequent treatment cost of crizotinib had a greater impact on ICER，but these parameters could not cause the reversal of basic analysis results. Probabilistic sensitivity analysis showed that with 1 time of China ’s per capita GDP in 2021 as the WTP threshold ，the probability of ensatinib group ’s treatment possessed economical efficiency was 100％. In the situational analysis ，ICER obtained by changing the ensatinib group ’s follow-up treatment regimen was －217 671.43 yuan/QALY，which was far below WTP threshold. CONCLUSIONS For Chinese patients with ALK positive-advanced NSCLC ，compared with commonly used the first-line treatment （crizotinib），ensartinib is economical and absolutely dominant.

Objective:To explore the criteria of general practice doctoral supervisors.Methods:The expert consultation questionnaire was formed by literature analysis. Experts in the field of general medicine from universities and tertiary hospitals in Shanghai were invited to participate in two rounds of Delphi consultation. The consultation content included the basic requirements and the importance evaluation of the selection criteria for general practice doctoral supervisors. Descriptive analysis and Analytic Hierarchy Process (AHP) were used to analyze the results of the study.Results:A total of 29 experts participated in the consultation, all with senior professional titles and doctoral degrees. The positive coefficient and expert authority coefficient of the two rounds of expert consultation were 1.0 and 0.925, respectively. The Kendall coordination coefficient of indicator importance evaluation were 0.436 and 0.397, respectively. The ethics, age, professional title, educational background and academic degree and diploma were considered to be included in the basic qualifications. The optimal standards for supervisor selection included teaching ability, scientific research ability, student training and team promotion ability that subdivided into 13 evaluation indexes.Conclusion:The basic qualifications and optimal standards for general practice doctoral supervisors have been preliminarily developed, which provides reference for selection of qualified general practice doctoral supervisors.

OBJECTIVE To eva luate the economy of loratinib versus crizo tinib in the first-line treatment of anaplastic lymphoma kinase （ALK）-positive advanced non-small cell lung cancer （NSCLC）from the perspective of China ’s health system ， and to provide reference for the product pricing and related medical decisions of the drug in other regions of China except for Hong Kong. METHODS Markov model and partition survival model both constructed based on the CROWN data （the simulation time limit was 10 years and the cycle period was 4 weeks）；the quality adjusted life year （QALY）was used as the outcome index to calculate the incremental cost-effectiveness ratio （ICER）. One-way sensitivity analysis ，probability sensitivity analysis and scenario analysis were used to verify the robustness of the results. RESULTS The basic analysis results based on Markov model showed that compared with crizotinib group ，the per capita cost of loratinib group increased by 17 867 588.63 yuan，the per capita utility increased by 1.76 QALYs，and the ICER was 10 152 038.99 yuan/QALY. The basic analysis results based on the partition survival model showed that compared with the crizotinib group ，the Δ 基金项目：江苏省博士后科研资助计划项目（No.2021K496C）； per capita cost of loratinib group increased by 18 009 592.54 2020年度高校哲学社会科学研究一般项目（No.2020SJA0070） yuan，the per capita utility increased by 1.74 QALYs，and the ＊硕士研究生 。研究方向 ：药物经济学 、卫生经济与政策 。 E-mail：sunlei_cpu@163.com ICER was 10 350 340.54 yuan/QALY. The results of one-way # 通信作者：教授，博士生导师。研究方向：药物经济学、卫生经 sensitivity analysis of the two models both showed that 济与政策。E-mail：ma86128@sina.com progression-free survival （PFS）state utility v alue，progression- ·1102· China Pharmacy 2022Vol. 33 No. 9 中国药房 2022年第33卷第9期 disease（PD）state utility value and loratinib cost had great influence on the results. The results of probability sensitivity analysis showed that when 1-3 times of China ’s per capita GDP in 2020 was taken as the willingness to pay threshold ，the probability of loratinib being economical was 0. The recommended unit price of loratinib per 100 mg was 657.10-815.60 yuan. CONCLUSIONS For patients with ALK-positive advanced NSCLC ，loratinib is more effective than crizotinib in the first-line treatment ，but it is not economical under the current price ；reasonably lowering the price of loratinib can increase the probability of its economy.

OBJECTIVE To ev aluate the economical efficiency of nivolumab versus everolimus in the second-line treatment of metastatic clear cell renal cell carcinoma. METHODS From the perspective of China ’s health system ，cost-effectiveness analysis of the two therapies was carried out by developing a three-state partitioned survival model. The clinical parameters were from the updated CheckMate 025 study，and the cost and health utility were from relevant websites and published literatures. The model adopted a 2-week cycle and a lifetime research time. The robustness of the results was verified by sensitivity analysis. The economical efficiency of two therapy schemes were evaluated in the scenario of model simulation time of 80 months and charitable drug donation scheme. RESULTS The results of basic analysis showed that compared with everolimus ，the incremental cost-effectiveness ratio （ICER）of nivolumab was 586 982.60 yuan/quality-adjusted life year （QALY），which was far higher than 3 times of China ’s per capita gross domestic product （GDP）in 2020. The results of single-factor sensitivity analysis showed that the 3 parameters that had the greatest impact on the economic evaluation results were the cost of nivolumab ，the utility value of nivolumab group and everolimus group in progressive disease state. The results of probability sensitivity analysis verified the robustness of the basic analysis results. Results of scenario analysis showed that in the first scenario analysis ，in which model simulation time lasted for 80 months，ICER of nivolumab was 417 204.52 yuan/QALY；in the second scenario analysis ，in which nivolumab charitable drug donation program for low-income people was considered ，ICER of nivolumab was 124 988.58 yuan/QALY. CONCLUSIONS Under the threshold of 1-3 times of China ’s per capita GDP in 2020，compared with everolimus ，it is not economical to use nivolumab as the second-line treatment for metastatic clear cell renal cell carcinoma ； nivolumab is economical when considering its charitable drug donation program for low-income people.

OBJECTIVE：To com pare the efficacy and safety of 5 direct antiviral agents in the treatment of chronic hepatitis C infection as glecaprevir （GLE）/pibrentasvir（PIB），ledipasvir（LDV）/sofosbuvir（SOF），SOF/velpatasvir（VEL），elbasvir（EBR）/ grazoprevir（GZR）compound preparation and danoprevir （DNV）+ peginterferon combined with ribavirin （P/R）. METHODS ： Retrieved from PubMed ，Embase，Cochrane Library ，Web of Science ，CNKI，VIP，Wanfang database and other databases ，RCTs about 5 direct antiviral agents in the treatment of chronic hepatitis C infection were collected during the inception to Jun. 2020. After literature screening and data extraction ，the quality of included literatures were evaluated with bias risk evaluation tool recommended by Cochrane system evaluator manual 5.1.0. Meta-analysis was performed by using Stata 15.0 software. RESULTS ： A total of 48 RCTs with 12 227 patients in trial group were included. Results of Meta-analysis showed that the descending order of sustained virological response （SVR）rate was GLE/PIB ＞LDV/SOF＞SOF/VEL＞EBR/GZR＞DNV+P/R；weighted SVR rates of GLE/PIB，LDV/SOF，SOF/VEL and EBR/GZ were more than 95％. The incidence of any severe adverse event and adverse event in ascending order was EBR/GZR ＜GLE/PIB＜SOF/VEL＜LDV/SOF＜DNV+P/R. The incidence of nausea/vomiting in ascending order was GLE/PIB ＜LDV/SOF＜EBR/GZR＜SOF/VEL＜DNV+P/R. The incidence of rash in ascending order was LDV/SOF ＜ GLE/PIB＜SOF/VEL＜EBR/GZR＜DNV + P/R. The incidence of insomnia from low to high was GLE/PIB ＜EBR/GZR＜SOF/ VEL＜LDV/SOF＜DNV+P/R. CONCLUSIONS ：GLE/PIB，LDV/SOF，SOF/VEL and EBR/GZR have higher and similar effective rates in the treatment of chronic hepatitis C ，especially the weighted SVR rate of GLE/PIB is the best ，and the safety of EBR/GZR and GLE/PIB is relatively better.

OBJECTIVE：To provide reference for impro ving the quality of programmed cell death protein 1 （PD-1）/ programmed cell death 1 ligand（PD-L1）inhibitors in the treatment of non-small cell lung cancer related pharmacoeconomic studies in China. METHODS ：Retrieved from Embase ，PubMed，Medline，Cochrane Library ，CNKI，Wanfang database ，VIP and other Chinese and English database ，cost-utility studies about PD- 1/PD-L1 inhibitors in the treatment of non-small cell lung cancer published during Jan. 2016-Jan. 2021 were collected. The data of the included studies were extracted. After the quality of the included studies was evaluated by using the Consolidated Health Economic Evaluation Reporting Standards list ，the relevant data were summarized and compared from the aspects of model framework ，model parameters and uncertainty analysis. RESULTS & CONCLUSIONS：A total of 17 studies were finally included ，the overall quality of them was high but the differences in methodology were great. Markov model or partition survival model based on three states was adopted for 16 studies. The time horizon ranged from 5 years to lifetime ；the cycle length ranged from 1 week to 6 weeks. A total of 8 studies used the standard parameter distribution method for parameter fitting ，and 7 studies additionally adopted other parameters estimation methods as KM curves or spline models. Eleven studies performed the validation of model extrapolation. All studies considered the direct medical costs and reported the incremental cost-effectiveness ratio using quality-adjusted life years as the health outcome. Sixteen studies conducted the deterministic sensitivity analysis and probabilistic sensitivity analysis to improve the stability of the model. It is suggested that studies should keep the integrity of the report ； format，choose the appropriate positive comparators ，selectthe health economic model and construct reasonable assumptions according to the available data format ， use Cholesky decomposition to explore the uncertainty of the parameter fitting ， perform the validation of extrapolation combined with external data and use the appropriate indirect comparison in the absence of the head-to-head clinical trials to improve the quality of related pharmacoeconomic studies in China.