Pharmacoeconomic evaluation of Keluoxin capsule combined with chemical medicine in the treatment of diabetic kidney disease / 中国药房

OBJECTIVE To evaluat e the cost-effectiveness of Keluoxin capsule combi ned with chemical medicine in the treatment of diabetic kidney disease （DKD）from the perspective of the whole society. METHODS Six-state Markov model with 1 year cycle and 40 years time horizon was constructed by means of secondary literature review ，medical record analysis of sample hospital and clinical expert consultation. The cost-effectiveness of Keluoxin capsule combined with chemical medicine versus chemical medicine alone for DKD was evaluated by taking the quality-adjusted life year （QALY）as the output index ，setting the discount rate as 5％，and taking one time domestic gross domestic product （GDP）per capita in 2020 of China as the judgement threshold of incremental cost-effectiveness ratio （ICER）. RESULTS Within 40 years，Keluoxin capsule combined with chemical medicine group spent 8 644.09 yuan per capita more than chemical medicine alone group ，and gained more 0.143 QALYs；ICER was 60 460.25 yuan/QALY，which was less than one times GDP per capita of China in 2020（72 447 yuan）. The results of sensitivity analysis showed that the annual days of using Keluoxin capsule ，the health utility value of DKD at early stage had a great influence on the results of cost-effectiveness analysis. The results of probabilistic sensitivity analysis suggested that the basic analysis results of this study were robust. CONCLUSIONS At the current price level ，Keluoxin capsule combined with chemical medicine is more cost-effective to treat DKD than chemical medicine alone. The dosage of Keluoxin capsule and health utility value should be paid attention in specific decision- bjmu.edu.cn making scenarios.

Real World Safety of Shujin Jianyao Pills in 3 033 Cases Under Intensive Hospital Monitoring Based on Active Monitoring / 中国实验方剂学杂志

ObjectiveTo further assess the safety of clinical application of Shujin Jianyao pills after marketing and find its potential risk factors as early as possible， to obtain the real world medication situation of Shujin Jianyao pills and its incidence of adverse reactions and clinical characteristics， and to explore the factors affecting the occurrence of adverse drug reactions （ADR）. MethodIn this study， prospective， large-sample， multi-center and intensive whole-hospital monitoring with continuous registration was carried out， combined with telephone follow-up visits 2-4 weeks after the end of medication， for whole treatment course monitoring among patients. In addition， the three-level quality control was strictly implemented in the monitoring process. The study used a proprietary electronic data management system for data management， and SAS 9.4 and R software were used for statistical analysis. ResultFrom May 2018 to July 2020， the study completed the safety monitoring of 3 033 patients taking Shujin Jianyao pills in 30 clinical departments of 25 hospitals in China. A total of 36 ADR cases （49 times） were confirmed by expert assessment on data and supervision quality and expert interpretation of ADR. ConclusionAccording to the World Health Organization （WHO）， the symptoms of adverse reactions were mainly classified into occasional adverse reactions （0.1%≤ADR<1%： abdominal distension， oral ulcer， dry mouth， constipation） and rare adverse reactions （0.01%≤ADR<0.1%： loss of appetite， rash， fatigue， increased ALT， increased creatinine， dizziness， stomachache， stomach distension， liver discomfort， pruritus， dysphoria， acid regurgitation， numbness in mouth， abdominal pain， sore throat， earache， tinnitus）. Moreover， through the synthetic minority oversampling technique （SOMTE） combined with logistic regression， the following factors might affect ADR： taking Shujin Jianyao pills for 1-14 days， aged 46-65， 66-80 and 81 and above as well as combined use of atorvastatin， cobamamide， calcitriol capsules， Gushukang capsules， glucosamine， nifedipine， methylcobalamin， metformin， Tenghuang Jiangu pills， Bugu tablets， and diclofenac sodium sustained-release tablets. This study provided a real world basis for the safety and standardized use of Shujin Jianyao pills in clinical practice.

Huangqi Sijunzi decoction for treating cancer-related fatigue in breast cancer patients: a randomized trial and network pharmacology study / 南方医科大学学报

OBJECTIVE@#To evaluate the clinical efficacy of Huangqi Sijunzi decoction (HQSJZD) for treating cancer-related fatigue (CRF) of spleen and stomach Qi deficiency type after chemotherapy in patients with breast cancer.@*METHODS@#A total of 94 breast cancer patients who developed CRF of spleen and stomach Qi deficiency type after chemotherapy were randomized into chemotherapy group (n=47) and traditional Chinese medicine (TCM) + chemotherapy group (n=47). The patients in chemotherapy group received the AC or EC regimen and non-drug interventions including psychological counseling, and those in TCM + chemotherapy group received oral administration of HQSJZD in addition to chemotherapy for 21 days as a treatment cycle, after which improvement of fatigue was assessed using Modified Piper Fatigue Scale. The active ingredients and targets of HQSJZD were screened using the TCM System Pharmacology Analysis Platform (TCMSP); the CRF- and breast cancer-related disease targets were retrieved based on data from the GeneCards, NCBI gene and OMIM databases to construct the component-target network and the protein-protein interaction (PPI) network. GO functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes KEGG pathway enrichment analysis of the target genes were performed to construct the component-disease-pathway-target biological network. The binding strength of the major drug ingredients and CRF key targets were predicted using AutoDock software.@*RESULTS@#The scores for somatic fatigue, emotional fatigue and cognitive fatigue, along with the overall fatigue score, showed more significant improvements in TCM+chemotherapy group than in chemotherapy group (P < 0.001), and the response rate reached 89.4% in the combined treatment group. We identified 250 targets for HQSJZD, 2653 CRF-related genes, 15 329 breast cancer-related genes and 161 prescription-disease intersected targets, from which topological analysis identified 66 potential key targets. GO and KEGG enrichment analyses predicted multiple pathways related with the disease. Molecular docking results suggested that the core ingredients of HQSJZD showed high affinities to the key targets AKT1, CASP3, IL6, JUN and VEGFA, among which AKT1 might be the most important target for HQSJZD to treat CRF.@*CONCLUSION@#HQSJZD can obviously improve CRF symptoms in breast cancer patients possibly by regulating multiple signaling pathways including PI3K-Akt through AKT1.

Preliminary experience with double-tract reconstruction combined with π-shaped esophagojejunal anastomosis after total laparoscopic proximal gastrectomy for the treatment of adenocarcinoma of esophagogastric junction / 中华胃肠外科杂志

Objective: To explore the feasibility and preliminary technical experience of the double-tract reconstruction combined with π-shaped esophagojejunal anastomosis after total laparoscopic proximal gastrectomy (TLPG) in the treatment of adenocarcinoma of esophagogastric junction (AEG). Methods: A descriptive case series study method was used. Clinical data of 12 AEG patients who underwent the double-tract reconstruction combined with π-shaped esophagojejunal anastomosis after TLPG from January 2021 to June 2021 at the Department of General Surgery, First Medical Center, PLA General Hospital were retrospectively analyzed. Among the 12 patients, the median tumor diameter was 2.0 (1.5-2.9) cm, and the pathological stage was T1-3N0-3aM0. All the patients routinely underwent TLPG and D2 lymph node dissection with double-tract reconstruction combined with π-shaped esophagojejunal anastomosis: (1) Double-tract reconstruction combined with π-shaped esophagojejunal anastomosis: mesentery 25 cm away from the Trevor ligament was treated, and an incision of about 1 cm was made on the mesenteric border of the intestinal wall and the right wall of the esophagus, two arms of the linear cutting closure were inserted, and esophagojejunal side-to-side anastomosis was performed. A linear stapler was used to cut off the lower edge of the anastomosis and close the common opening to complete the esophagojejunal π-shaped anastomosis. (2) Side-to-side gastrojejunostomy anastomosis: an incision of about 1 cm was made at the jejunum to mesenteric border and at the greater curvature of the remnant stomach 15 cm from the esophagojejunostomy, and a linear stapler was inserted to complete the gastrojejunostomy side-to-side anastomosis. (3) Side-to-side jejunojejunal anastomosis: an incision of about 1 cm was made at the proximal and distal jejunum to the mesangial border 40 cm from the esophagojejunostomy, and two arms of the linear stapler were inserted respectively to complete the side-to-side jejunojejunal anastomosis. A midline incision about 4-6 cm in the upper abdomen was conducted to take out the specimen, and an abdominal drainage tube was placed, then layer-by-layer abdominal closure was performed.@*INDICATIONS@#(1) adenocarcinoma of esophagogastric junction (Seiwert type II-III) was diagnosed by endoscopy and pathological examination; (2) ability to preserve at least 1/2 of the distal stomach after R0 resection of proximal stomach was evaluated preoperatively.@*CONTRAINDICATIONS@#(1) evaluation indicated distant metastasis of tumor or invasion of other organs; (2) short abdominal esophagus or existence of diaphragmatic hiatal hernia was assessed during the operation; (3) mesentery was too short or the tension was too high; (4) existence of severe comorbidities before surgery; (5) only palliative surgery was required in preoperative evaluation; (6) poor nutritional status.@*MAIN OUTCOME MEASURES@#operation time, intraoperative blood loss, postoperative complications, time to first flatus and time to start liquid diet, postoperative hospital stay, operation cost, etc. Continuous variables that conformed to normal distribution were presented as mean ± standard deviation, and those that did not conform to normal distribution were presented as median (Q1,Q3). Results: All the patients successfully completed TLPG with double-tract reconstruction combined with π-shaped esophagojejunal anastomosis, and postoperative pathology showed that no cancer cells were found on the upper incision margin. The operation time was (247.9±62.4) minutes, the median intraoperative blood loss was 100.0 (62.5, 100.0) ml, no intraoperative blood transfusion was required, the incision length was (4.9±1.0) cm, and the operation cost was (55.5±0.7) thousand yuan. The median time to start liquid diet was 1.0 (1.0, 2.0) days, and the mean time to flatus was (3.1±0.9) days. All the patients were discharged uneventfully. Only 1 patient developed postoperative paralytic ileus and infectious pneumonia with Clavien-Dindo classification of grade II. The patient recovered after conservative treatment. There was no surgery-related death. The postoperative hospital stay was (8.3±2.1) days. Conclusion: The double-tract reconstruction combined with π-shaped esophagojejunal anastomosis after TLPG is safe and feasible, which can minimize surgical trauma and accelerate postoperative recovery.

A comparative study on short-term outcomes and quality of life for gastric cancer patients between totally laparoscopic total gastrectomy using an endoscopic linear stapler and laparoscopic-assisted total gastrectomy using a circular stapler / 中华胃肠外科杂志

Objective: To explore the differences of short-term outcomes and quality of life (QoL) for gastric cancer patients between totally laparoscopic total gastrectomy using an endoscopic linear stapler and laparoscopic-assisted total gastrectomy using a circular stapler. Methods: A retrospective cohort study was conducted. Clinicopathological data of patients with stage I to III gastric adenocarcinoma who underwent laparoscopic total gastrectomy from January 2017 to January 2020 were retrospectively collected. Those who were ≥80 years old, had serious complications that could affect the quality of life, underwent multi-organ resections, palliative surgery, emergency surgery due to gastrointestinal perforation, obstruction, bleeding, died or lost to follow-up within 1 year after surgery were excluded. A total of 130 patients were enrolled and divided into circular stapler group (CS group, 77 cases) and linear stapler group (LS group, 53 cases) according to the surgical method. The differences of age, gender, body mass index, number of comorbidities, history of abdominal surgery, ASA, tumor location, degree of differentiation, tumor length, tumor T stage, tumor N stage, tumor pathological stage and preoperative quality of life between the two groups were not statistically significant (all P>0.05). The observation indicators: (1) Surgery and postoperative conditions. (2) Postoperative complications: Any adverse conditions that require conservative treatment or surgical intervention after surgery were defined as postoperative complications, of which, complications occurring within 30 days after surgery were defined as early complications; complications occurring within 30 days to 1 year after surgery were defined as late complications. (3) Postoperative quality of life was assessed by the quality of life core scale (QLQ-C30) and gastric cancer specific module scale (QLQ-STO22). The higher the scores of functional scales and global health status, the better the corresponding quality of life. The higher the scores of symptoms scales, the worse the corresponding quality of life. Results: (1) Surgery and postoperative conditions: Compared with the CS group, the LS group presented less intraoperative blood loss [50.0 (50.0-100.0) ml vs. 100.0 (100.0-100.0) ml, Z=-3.111, P=0.002] and earlier time to flatus [(3.1±0.8) days vs. (3.5±1.1) days, t=-2.490, P=0.014]. However, there were no statistically significant differences between two groups of patients in terms of operation time, time to start a liquid diet and postoperative hospital stay (all P>0.05). (2) Postoperative complications: The early complication rates of the CS group and the LS group were 22.1% (17/77) and 18.9% (10/53), respectively, while the late complication rate were 18.2% (14/77) and 15.1% (8/53), respectively, whose differences were not statistically significant (all P>0.05). (3) Postoperative quality of life: After 1-year follow-up, 7 (5.4%) patients were lost, including 5 in CS group and 2 in LS group. One year after operation, the QLQ-C30 scale showed that the score of financial difficulty of the LS group was significantly higher than that of the CS group [33.3 (0 to 33.3) vs.0 (0 to 33.3), Z=-1.972, P=0.049] with statistically significant difference, and there were no statistically significant differences in the scores of other functional fields and symptom fields between the two groups (all P>0.05). The QLQ-STO22 scale showed that the scores of dysphagia [0 (0 to 5.6) vs. 0 (0 to 11.1), Z=-2.094, P=0.036] and eating restriction were significantly lower [0 (0 to 4.2) vs. 0 (0 to 8.3), Z=-2.011, P=0.044] in patients of the LS group than those of the CS group. There were no significant differences in scores of other symptoms between two groups (all P>0.05). Conclusions: Compared with the circular stapler, the esophagojejunostomy with linear stapler for gastric cancer patients can reduce intraoperative blood loss, shorten the time to flatus after operation, alleviate the symptoms of dysphagia and eating restriction but increase the economic burden to a certain degree.

Effectiveness of quality of care for patients with type 2 diabetes in China: findings from the Shanghai Integration Model (SIM) / 医学前沿

This cross-sectional study aimed to investigate the quality of care of diabetes in Shanghai, China. A total of 173 235 patients with type 2 diabetes in 2017 were included in the analysis. Profiles of risk factors and intermediate outcomes were determined. The patients had a mean age of 66.43 ± 8.12 (standard deviation (SD)) years and a mean diabetes duration of 7.95 ± 5.53 (SD) years. The percentage of patients who achieved the target level for HbA1c (< 7.0%) was 48.6%. Patients who achieved the target levels for blood pressure (BP) < 130/80 mmHg and low-density lipoprotein-cholesterol (LDL-c) < 2.6 mmol/L reached 17.5% and 34.0%, respectively. A total of 3.8% achieved all three target levels, and the value increased to 6.8% with an adaptation of the BP target level (< 140/90 mmHg) for those over 65 years. Multivariable analysis identified the factors associated with a great likelihood of achieving all three target levels: male, young age, short diabetes duration, low body mass index, macrovascular complications, no microvascular complications, prescribed with lipid-lowering medication, and no prescription of antihypertensive medication. In conclusion, nearly 50% and one-third of the patients with diabetes met the target levels for HbA1c and LDL-c, respectively, with a low percentage achieving the BP target level. The percentage of patients who achieved all three target levels needs significant improvement.

Optimization of formulation of paclitaxel nanosuspension encapsulated by erythrocyte membrane based on Box-Behnken method / 中国中药杂志

In view of the longevity and innate immune escape of red blood cells, this study designed the red blood cell membrane-coated paclitaxel nanosuspension [RBC-(PTX)NS] and investigated its physicochemical properties and antitumor effect in vitro. Paclitaxel nanosuspension [(PTX)NS] was prepared by ultrasonic precipitation and then RBC-(PTX)NS by ultrasonic coating. The formulation of(PTX)NS was optimized with Box-Behnken method and indexes of particle diameter, zeta potential, and stability. The morphology, particle diameter, stability, in vitro dissolution, and antitumor effect of(PTX)NS and RBC-(PTX)NS were characterized. The results showed that the particle diameter and zeta potential were(129.38±0.92) nm and(-22.41±0.48) mV, respectively, for the optimized(PTX)NS, while(142.5±0.68) nm and(-29.85±0.53) mV, respectively, for RBC-(PTX)NS. Under the transmission electron microscope,(PTX)NS was spherical and RBC-(PTX)NS had obvious core-shell structure. RBC-(PTX)NS remained stable for 5 days at 4 ℃. The in vitro dissolution test demonstrated that the cumulative release rate of RBC-(PTX)NS reached 79% within 20 min, which was significantly higher than that(25%) of(PTX)NS(P<0.05). As evidenced by MTT assay, RBC-(PTX)NS highly inhibited the proliferation of HepG2 cells in a dose-dependent manner. The cell membrane-coated nano-preparation preparation method is simple and reproducible. It improves the solubility of PTX and endows RBC-(PTX)NS with higher stability and stronger cytotoxicity. Thus, it is a new method for the delivery of PTX via nanocrystallization.

Clinical comprehensive evaluation of Tianshu Capsules in treatment of migraine (syndrome of blood stasis blocking collaterals and syndrome of ascendant hyperactivity of liver Yang) / 中国中药杂志

This study systematically sorted out the existing studies about Tianshu Capsules in the treatment of migraine(syndrome of blood stasis blocking collaterals, syndrome of ascendant hyperactivity of liver Yang), and conducted comprehensive clinical evaluation through "6+1" dimensions of safety, effectiveness, economy, innovation, suitability, accessibility, and characteristics of traditional Chinese medicine(TCM) to embody the advantages and characteristics and clarify the precise clinical position of Tianshu Capsules. The value of each dimension was calculated via health technology assessment, the multi-criteria decision analysis(MCDA) mo-del and CSC v2.0 software. The results were graded into four levels of A, B, C, or D from high to low. According to the available studies, Tianshu Capsules had low and controllable risks, with the safety rated as A. The drug has obvious clinical significance in the treatment of migraine(syndrome of blood stasis blocking collaterals, syndrome of ascendant hyperactivity of liver Yang), with the effectiveness rated as A. It has clear economic results, with the economy rated as B. The clinical innovation, service system innovation, and industrial innovation are all good, and thus the innovation of Tianshu Capsules is grade A. The drug can meet clinical medication demand of medical care and patients, and thus its suitability is grade A. In view of the reasonable drug price, affordability, and availability, the accessibility is grade A. The prescription originated from the Daxiong Pills recorded in the classic Comprehensive Recording of Sage-like Benefit. In clinical trials, 4 675 patients have used Tianshu Capsules, which indicates rich experience in human administration, and the characteristics of traditional Chinese medicine is grade B. The statutory drug information complies with national stan-dards, and the non-statutory information is standard and accurate. Based on the comprehensive evaluation results of various dimensions of evidence, the clinical value of Tianshu Capsules in the treatment of migraine(syndrome of blood stasis blocking collaterals and syndrome of ascendant hyperactivity of liver Yang) is class A. According to the Comprehensive Clinical Evaluation Management Guidelines of Drugs(trial version 2021) issued by the National Health Commission of the People's Republic of China, we recommend that Tianshu Capsules treating migraine can be transformed into relevant policy results for clinical medication management according to procedures.

Clinical comprehensive evaluation of Ginkgolide Injection in treatment of cerebral infarction / 中国中药杂志

This clinical value-oriented comprehensive evaluation of drugs was carried out in accordance with Guidelines for Management of Comprehensive Clinical Evaluation of Drugs(trial version 2021), with the qualitative and quantitative evaluation methods adopted. Based on the evidence-based medicine, epidemiology, clinical medicine, pharmacoeconomics, mathematical statistics, and health technology evaluation(HTA), the clinical value of Ginkgolide Injection was evaluated from the "6+1" dimension by giving weight to the criterion level and index level and calculating with multi-criteria decision analysis(MCDA) model and CSC v2.0. After entering the market, Ginkgolide Injection has been subjected to phase Ⅳ clinical trial, spontaneous reporting system(SRS)-based data monitoring, systematic review and Meta-analysis, acute toxicity and long-term toxicity assays, active monitoring, and RCTs, and the evidence of safety was sufficient. The results of active monitoring showed that the incidence of adverse reactions was 0.09%(rare), mainly manifested as flushing, dizziness, rash, nausea, and vomiting. According to the nested case-control study, the adverse reactions of this drug had nothing to do with the product batch, implying that the drug quality was controllable. The adverse reactions mainly resulted from the pharmacodynamic reactions. Because the drug was effective in resisting platelet aggregation, the resulting adverse reactions such as flushing, dizziness, headache, and phlebitis were caused by vasodilation. Skin rash and gastrointestinal symptoms were mainly attributed to the patients' sensitivity to drugs and their own allergic constitution. According to the sufficiency of evidence and the incidence of adverse reactions in the safety research, the safety of Ginkgolide Injection was grade A. The results of Meta-analysis showed that Ginkgolide Injection combined with conventional western medicine was superior to conventional western medicine in improving the clinical effective rate, neurological function score, and activity of daily living score of patients with cerebral infarction. The validity evidence was evaluated according to the PICO principle to be high. According to the GREAD evaluation principle, the quality of such evidence as clinical effective rate, National Institute of Health stroke scale(NIHSS), and Barthel Index(BI) was evaluated, and the results demonstrated that the evidence quality of clinical effective rate and activity of daily living score was medium. The effectiveness of Ginkgolide Injection was grade A. According to the economic report of Ginkgolide Injection, it had short-term and long-term pharmacoeconomic advantages in the treatment of ischemic stroke, and the economic evidence value was good. According to the CASP economic evaluation checklist, the overall quality evaluation results of the economic report are basically clear. To be specific, the economic evidence quality was high. Based on the comprehensive economic evidence quality and economic value, the economy of this drug was grade A. The innovation of this product was evaluated from three aspects: clinical innovation, enterprise service system innovation, and industrial innovation. Ginkgolide Injection could be used 24 h after intravenous thrombolysis for improving patients' neurological function without increasing bleeding, indicating its important clinical innovation. There were many innovations in ensuring drug supply, especially at the grass roots, drug safety, effectiveness, and reasonable price, which has provided reference for establishing enterprise philosophy, managing drug resources, developing process and technology, and determining enterprise management and marketing. Therefore, its innovation was grade A. The drug had no special medication plan in use, exhibiting good suitability for doctors, nurses, and patients. The suitability was grade B. Compared with similar drugs, its price was at a medium level, meaning good affordability, sufficient production capacity, and easy accessibility. Its accessibility was therefore grade B. This drug belonged to Chinese medicinal injection. The large-sample real-world research revealed rich human use experience, so it was grade C for the traditional Chinese medicine characteristic. According to the comprehensive evaluation, the clinical value of Ginkgolide Injection in the treatment of cerebral infarction fell into class A. It is suggested that it can be transformed into the relevant policy results of basic clinical medication management according to the procedure.

Clinical comprehensive evaluation of Reyanning Mixture in treatment of acute upper respiratory tract infection (heat-toxin attacking lung syndrome) / 中国中药杂志

This study systematically sorted out the evidence data of the safety, effectiveness, economy, innovation, suitability, accessibility, and characteristics of traditional Chinese medicine(TCM) of Reyanning Mixture in the treatment of acute upper respiratory tract infection(heat-toxin attacking lung syndrome) with the qualitative and quantitative evaluation methods adopted. Based on evidence-based medicine, epidemiology, clinical medicine, evidence-based pharmacy, pharmacoeconomics, and health technology evalua-tion(HTA), the clinical value of Reyanning Mixture was evaluated using multi-criteria decision analysis(MCDA) model, Chinese patent medicine clinical evidence, and value evaluation software(CSC v2.0). The SRS monitoring data, Meta-analysis, and other safety evidence showed that the main adverse reactions of Reyanning Mixture were nausea, diarrhea, and rash, and no serious adverse reactions were found. The pharmacovigilance system was sound, and the system was perfect. There was no recall, notification, or interview for unqualified products. Based on the existing research, the evidence was sufficient, and the risk was controllable. Hence, its safety was grade A. Meta-analysis showed that in the treatment of acute upper respiratory tract infection, Reyanning Mixture combined with Amoxicillin Capsules was better than Amoxicillin Capsules alone in shortening the complete fever relief time and improving the cure rate. Besides, it was superior to Shuanghuanglian Granules in shortening the complete fever relief time, cough relief time, nasal congestion relief time, and pharyngeal congestion relief time. The Meta-analysis was conducted based on AMSTAR standard, and its ove-rall quality was proved good. The evidence quality in GRADE system evaluation was medium and low. The quality of evidence was medium, and the clinical value was obvious. Hence, its effectiveness was grade A. The results of pharmacoeconomic research showed that compared with Amoxicillin Capsules, Reyanning Mixture alone or in combination with Amoxicillin Capsules had cost-effectiveness advantages in the treatment of acute upper respiratory tract infection, and the results were stable in sensitivity analysis. According to the CASP economic evaluation checklist, the research problems were clear and the results were reliable. As revealed by the comprehensive evaluation, the evidence quality was sufficient and the result was clear. Its economy was grade B. Reyanning Mixture had multiple therapeutic targets like anti-virus, anti-bacteria, antipyresis, and anti-cough, with good clinical innovation. There were many innovative initiatives in ensuring drug supply, especially at the grass roots, drug safety, and effectiveness, and also multiple innovative contributions to production technology, quality control, scientific and technological research and development, and enterprise management and marketing. Therefore, its innovation was grade B. The dosage form of Reyanning was mixture, which made it convenient for storage and transportation. The usage was easy to be mastered and accepted by doctors and nurses, exhibiting good suitability for clinicians, nurses, pharmacists, and patients who received this drug and basically meeting the needs of clinical medication. The suitability was grade B. The average daily cost of this drug was 8.082 yuan, and the price was low. The treatment cost accounted for a small proportion of the annual disposable income of urban and rural residents, indicating that it was affordable. Reyanning Mixture was available in 31 provinces, cities and autonomous regions, covering 6 910 hospitals. The allocation of hospitals at all levels was more than 50%. There was no shortage or supply restriction of medicinal material resources. The annual production capacity was sufficient to meet the supply demand, so its accessibility was grade A. Reyanning Mixture, sourced from "pneumonia Ⅲ", has been subjected to a real-world study of its clinical application, with 4 367 cases involved, and the characteristic of TCM was grade B. The comprehensive evaluation results demonstrated that the clinical value score of Reyanning Mixture in the treatment of acute upper respiratory tract infection(heat-toxin attacking lung syndrome) was 0.80, making it rated class A. According to the Guidelines for Management of Comprehensive Clinical Evaluation of Drugs(trial version 2021), it is recommended to convert it into the relevant policy results of basic clinical medication management according to the procedures.

Clinical comprehensive evaluation of Guanxin Shutong Capsules in treatment of coronary heart disease angina pectoris with heart blood stasis syndrome / 中国中药杂志

This study aims to comprehensively summarize articles on the treatment of coronary heart disease angina pectoris with heart blood stasis syndrome(CHD-AP-HBSS) by Guanxin Shutong Capsules(GSC), and comprehensively evaluate the evidence and value of the formula in "6+1" dimensions based on multi-criteria decision analysis(MCDA) model and Guidelines for Management of Comprehensive Clinical Evaluation of Drugs(trial version 2021) with quantitative and qualitative methods, which is expected to highlight the clinical characteristics and advantages of the prescription and serve as a reference for medical and health departments. The dimensions are grade A, B, C, or D. In terms of safety, according to the reports from the spontaneous reporting system of National Center for ADR Monitoring, and literature analysis, GSC mainly results in the adverse reactions of mild or moderate nausea, diarrhea, rash, palpitation, and headache, with favorable prognosis in patients. Nevertheless, severe adverse reactions have been reported after marketing. Thus, additional evidence for its safety should be accumulated, and the current safety is grade B. Meta-analysis proves that GSC in combination with conventional treatment is superior to conventional treatment alone in alleviating AP and symptoms indicated by electrocardiogram(ECG). Therefore, the effectiveness of the medicine is grade A. As for the pharmacoeconomic value, based on the assumption that the per capita disposable income in 2020 is the willingness-to-pay threshold, it is more economical for CHD-AP patients to use GSC combined with conventional treatment than conventional treatment alone. However, as the currently available clinical parameters fail to support the difference in indirect cost between the two groups, the accuracy in the cost of intervention plan needs to be further improved. Therefore, the economy of the prescription is grade B. GSC has been awarded 13 national invention patents and 1 utility model patent, and won a lot of national and provincial patent awards, marking the enterprise service awareness and innovativeness. As a result, it is grade A in aspect of innovation. A questionnaire on the suitability of GSC suggests that publicity and promotion influence patients' choice and thus additional efforts should be made in this aspect. The suitability of this formula is grade B. Both rural and urban residents can afford the medicine for the whole course and the price is close to that of similar Chinese patent medicines. In addition, it is accessible regardless of season and place, so accessibility is grade A. As a Mongolian empirical formula destined to treat heart stabbing pain, it has the effects of activating blood and resolving stasis, dredging channels and activating collaterals, and moving Qi to relieve pain, and boasts the empirical evidence of more than 2 000 human cases. With prominent characteristics of traditional Chinese medicine, it is grade B. Based on the MCDA model and CSC v2.0, GSC is comprehensively class A in the treatment of CHD-AP-HBSS. The result can serve as a reference for basic clinical medication management.

Clinical comprehensive evaluation of Qilong Capsules in treatment of ischemic stroke with Qi deficiency and blood stasis syndrome / 中国中药杂志

The present study systematically sorted out the existing research on Qilong Capsules in the treatment of ischemic stroke with Qi deficiency and blood stasis syndrome and comprehensively evaluated its clinical evidence and value to highlight the advantages and characteristics of products and provide references for the decision-making of national pharmaceutical management departments. Based on the evidence-based medicine, epidemiology, clinical medicine, evidence-based pharmacy, and pharmacoeconomics, the qualitative and quantitative evaluation of "6+1" dimensions of safety, effectiveness, economy, innovation, suitability, and accessibility, as well as characteristics of traditional Chinese medicine(TCM) was performed with multi-criteria decision analysis(MCDA) mo-del using the information, such as public data, literature data, pharmaceutical research, and questionnaire survey, and CSC v2.0 was used to calculate the clinical value of Qilong Capsules. The evaluation results were grade A, B, C, or D. Spontaneous reporting system(SRS) monitoring data, literature reports, clinical trials, and other multi-source safety evidence showed that the main adverse reactions of this drug included dry mouth, nausea, and rash, and no severe adverse reactions was found. The evidence was sufficient with small and controllable known risks, and the safety was grade A. Meta-analysis showed that Qilong Capsules combined with conventional western medicine in the treatment of acute ischemic stroke was superior to the control group in improving neurological deficits, clinical total response rate, patients' activities of daily living, and hemorheological indexes. The level of evidence was high with manifest clinical significance, and the effectiveness was grade A. The results of pharmacoeconomic research showed that Qilong Capsules combined with conventional western medicine in the treatment of ischemic stroke were advantageous in cost-effectiveness as compared with conventional western medicine alone, but the incremental effect was not significant. The quality evaluation results of the economic report were comparatively clear, and the economy was grade B. Aiming at major cerebrovascular diseases in the society and giving full play to the advantages of TCM, Qilong Capsules focused on the inheritance of classics and scientific and technological innovation, and innovation was grade B. The results of the questionnaire survey showed that the technical characteristics and drug application could meet the medication needs of clinical doctors and patients, and the suitability was grade B. The price level of this drug was comparatively high and the affordability was good since the treatment cost accounted for a small proportion of disposable income. The drug accessibility was good with a wide range of drug sales, sufficient production capacity, and sustainable medicinal materials resources, and was grade B. This drug was derived from the classic prescription Buyang Huanwu Decoction with rich experience of human application, which could regulate Qi and blood circulation, and the section of TCM characteristics was grade B. Based on the evidence evaluation results of "6+1" dimensions of Qilong Capsules, the comprehensive evaluation of clinical value was class A. It is suggested that it can be transformed into relevant policy results of basic clinical medication management according to procedures.

Pharmacoeconomic evaluation of Qidong Yixin Oral Liquid in treatment of viral myocarditis (Qi-Yin deficiency syndrome) with TreeAge Pro / 中国中药杂志

To evaluate the pharmacoeconomic value of Qidong Yixin Oral Liquid in the treatment of viral myocarditis(Qi-Yin deficiency syndrome) by supplementing Qi, nourishing the heart, calming the mind, and relieving palpitation, the present study performed the Meta-analysis based on the published papers on Qidong Yixin Oral Liquid by AMSTAR and carried out pharmacoeconomic evaluation using TreeAge Pro by the cost-effectiveness analysis. The results showed that the quality of the included papers was good. After four weeks of treatment, Qidong Yixin Oral Liquid combined with the conventional treatment regimen was superior to the conventional treatment in improving creatine kinase isoenzyme, and the difference was statistically significant. Furthermore, the treatment cost was also higher than that of conventional treatment, with an incremental cost-effectiveness ratio of CNY 95.89, accounting for 0.30% of per capita disposable income. The results of sensitivity analysis showed that the research results were robust. Therefore, based on the assumption that the per capita disposable income in 2020 was the threshold of patients' willingness to pay, it is more economical for patients with viral myocarditis to use Qidong Yixin Oral Liquid combined with conventional secondary prevention regimen than conventio-nal secondary prevention regimen alone. The economic evaluation of Qidong Yixin Oral Liquid in the treatment of viral myocarditis will help physicians and patients choose optimal treatment options, improve rational clinical medication, and provide references for the efficient allocation and utilization of medical resources in China.

Monitoring mechanism for high group behavior based on the big data diagnosis-intervention packet / 中华医院管理杂志

One of the challenges to diagnosis-intervention packet is how to detect and avoid the institutional behavior of pursuing a higher score group. Based on the analysis method of big data, the authors analyzed the objective distribution characteristics of the treatment methods corresponding to a diagnosis, and compared the distribution of diseases with high and low scores in the region to find out the selection trend of treatment methods for the same diagnosis in various hospitals. Combined with hospital positioning, the authors found out whether there was a tendency of pursuing a higher score group. Scientific support will be provided for the reasonable payment of medical insurance expenses and the development planning of hospitals.

Research on price-formation in the big data diagnosis-intervention packet / 中华医院管理杂志

Objective:To explore the price formation method and price standard in the big data diagnosis-intervention packet.Methods:The expenditure data and income data of 95 medical institutions in Shanghai in 2018 were used for analysis, including 33 municipal hospitals and 62 district hospitals. After using the standardized data of disease score, the medical institutions in the region were divided into four quadrants with the regional average of unit price per index and cost per index as the coordinate axis. The best quadrant of income and cost was found out, namely the high quality range. The geometric center was calculated in the high quality range, and the unit price per index of the geometric center was taken as the cost standard.Results:For the district hospitals, there were 20 hospitals in the first quadrant, 8 in the second quadrant, 24 in the third quadrant and 10 in the fourth quadrant; For the municipal hospitals, there were 7 hospitals in the first quadrant, 5 in the second quadrant, 12 in the third quadrant and 9 in the fourth quadrant. In the third quadrant, the average income and cost of medical institutions were lower than the average of the city, and the income could cover the cost. The third quadrant was the high quality range. The unit price per index of the third quadrant geometric center of district hospitals was 14 115.4 yuan, and that in municipal hospitals was 15 559.1 yuan, which could be used as the corresponding cost standard.Conclusions:The price discovery mechanism based on objective data and high-quality interval geometric center method can remove the impact of unreasonable charges or unreasonable behavior on medical income, and reflect the guidance of the standard price of medical insurance payment.

The big data diagnosis-intervention packet payment method: experience from Shanghai and Guangzhou / 中华医院管理杂志

Medical insurance payment model is transforming from project-based purchases to service bundle-based strategic purchases. The new form of bundled purchases should found on a scientifically-led design process of such bundles. The core to bundled purchase would be the payment standard, and the key to its success would be process control. Establishment of such a foundation, a core, and a key, would promote the current price standards, and lead service providers to a standardized medical service standard, so as to ensure a precise rewarding system of payment and service. The big data diagnosis-intervention packet(DIP)is able to fulfill mentioned ambitions by integrating insurance payment and supervision into one management. DIP is a full-process payment mode that encompasses pre-service estimation, in-service process control, post-service grading, and resource allocation. It is an innovative practice in line with China′s national conditions for the modern governance of medical security and medical services.

Biomarkers and Target Mechanisms of Epimedii Folium Intervention on Breast Cancer Stem Cells Based on Chip Analysis and Network Pharmacology / 中国实验方剂学杂志

Objective:To elucidate the potential molecular markers and drug-compound-target mechanism of Epimedii Folium intervention on breast cancer stem cells（BCSCs） through chip analysis combined with network pharmacology and experimental validation. Method:Relevant drug information was retrieved in Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） to obtain the active components and potential targets of Epimedii Folium. "Breast Cancer Stem Cells" were searched in Gene Expression Omnibus（GEO）database，and GSE98239 chip data were obtained through analysis and screening. Then GEO2R online analysis tool was used to obtain the differential genes to draw differential gene heat map and volcano map. The differential gene network map of Epimedii Folium intervention for breast cancer stem cells was constructed by Cytoscape 3.8.0，and Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG）enrichment analysis of drug and disease genes were performed. Human breast cancer MDA-MB-231 cells were divided into 20%，40%，60% Epimedii Folium drug-containing serum group and control group. Cell counting kit-8（CCK-8），and Western blot were used to detect the effect of Epimedii Folium drug-containing serum intervention on cell activity and target protein expression in breast cancer cells. Result:Twenty-three active components including flavones，sterols，alkaloids and sesquiterpenoids were obtained from Epimedii Folium. It was found that Epimedii Folium interacted with B-cell lymphoma-2-like protein 1（BCL2L1），matrix metallopeptidase 2（MMP2），prostaglandin-endoperoxide synthase 2（PTGS2），vascular endothelial growth factor A（VEGFA），transforming growth factor beta receptor 1（TGFBR1） and other pivotal genes in breast cancer stem cells，participated in the induction of new angiogenesis and cell migration，enabled the continuous self-renewal of BCSCs，decreased apoptosis and cell migration，thus promoting the recurrence and metastasis of breast cancer. KEGG results showed that Epimedii Folium intervened in multiple differential expressed genes（DEGs）of transforming growth factor-<italic>β</italic>（TGF-<italic>β</italic>），vascular endothelial growth factor（VEGF），phosphoinositide 3kinase/protein kenase B（PI3K/Akt），mitogen-activated protein kinese（MAPK）and mammalian target of rapamycin（mTOR）subpathways in cancer signaling pathways to exert its efficacy in intervening breast cancer stem cells. Experiments showed that the survival rate of breast cancer cells was significantly reduced and the expression levels of TGFBR1 and Smad2 in breast cancer cells significantly decreased after the intervention of Epimedii Folium drug-containing serum（<italic>P</italic><0.01）. Conclusion:Several components in different concentrations of drug-containing serum of Epimedii Folium can synergistically act on target differentially expressed genes of breast cancer stem cells，and inhibit the proliferation of breast cancer cells by down-regulating the expression levels of TGFBR1，a key molecule in the TGF-<italic>β</italic> pathway，and Smad2，a downstream signal.

The development status and analysis of Traditional Chinese Medicine in Malaysia / 国际中医中药杂志

Malaysia is a multi-ethnic and multi-cultural constitutional monarchy and federal system located in Southeast Asia. The top three diseases that cause deaths are ischemic heart disease, lower respiratory tract infections and stroke. Lower respiratory tract infections, colorectal cancer and Alzheimer’s disease have been the fastest growing diseases in recent years. The health insurance system complements public and private health care system. Traditional medicine in Malaysia includes Malaysian Medicine, Traditional Chinese Medicine (TCM), Indian Medicine, Islamic Medicine and homeopathy. Although TCM, such as acupuncture, has not been covered by health insurance, it is widely used under the impetus of the local Chinese people. At present, in Malaysia, the TCM public acceptance and education need promotion, and scientific researches need to be improved. It is hoped that in the future, the development of TCM in Malaysia will be better developed and disseminated by promoting TCM relevant legislation, increasing public awareness, focusing on education and training, and carrying out international scientific research cooperation.

Risk factors of postoperative complication after total gastrectomy in advanced gastric cancer patients receiving neoadjuvant chemotherapy / 中华胃肠外科杂志

Objective: At present, there are few studies focusing on the factors short-term complications after total gastrectomy in patients with advanced gastric cancer receiving neoadjuvant chemotherapy (NACT). The purpose of this study is to provide a reference for clinical prevention of complications in these patients. Methods: A retrospective case-control study was conducted. Case inclusion criteria: (1) clinical stage II-III gastric cancer diagnosed by preoperative gastroscopy, pathology, abdominal CT, EUS or PET-CT; (2) evaluated suitable for NACT by MDT discussion; (3) no previous history of other malignant tumors and no concurrent tumor; (4) undergoing total gastrectomy+ D2 lymphadenectomy after NACT. Exclusion criteria: (1) age <18 or >80 years old; (2) severe concurrent diseases, and ASA classification>grade III; (3) stump gastric cancer or history of gastric surgery; (4) incomplete clinicopathological data. According to the above criteria, clinicopathological data of 140 advanced gastric cancer patients who underwent total gastrectomy after NACT in Chinese PLA General Hospital between June 2012 and June 2019 were collected, including 109 males and 31 females with mean age of (56.9±11.4) years and body mass indey (BMI) of (23.3±3.1) kg/m(2). Logistic analysis was used to analyze the relationship between postoperative complication and clinicopathological data. Factors in univariate analysis with P<0.05 were included in the multivariate analysis. Results: Postoperative complications (Clavien-Dindo classification ≥ II) occurred in 35 cases (25.0%) and severe complications (Clavien-Dindo classification ≥ IIIa) occurred in 4 cases (2.9%), including 1 case of esophago-jejunal anastomotic leakage, 1 case of vena cava thrombosis, 1 case of pleural effusion, 1 case of septic shock during perioperative days resulting in death. Univariate analysis showed that BMI (P=0.011), cycle of NACT (P=0.027), tumor diameter (P=0.021), and vascular invasion (P=0.033) were associated with postoperative complication within 30 days, while open/laparoscopic total gastrectomy were not associated with postoperative complication (P=0.926). Multivariate analysis revealed that BMI ≥ 25 kg/m(2) (OR=3.294, 95% CI: 1.343-8.079, P=0.009) and < 4 cycles of NACT (OR=2.922, 95% CI: 1.217-7.016, P=0.016) were independent risk factors for postoperative complication. The 3-year overall survival rates of patients with or without complication were 54.4% and 64.0%, respectively (P=0.395), and 3-year disease-free survival rates were 47.4% and 52.9%, respectively (P=0.587). Conclusions: Higher BMI and fewer cycles of NACT are independent risk factors of postoperative complication in advanced gastric cancer patients undergoing total gastrectomy after NACT. No obvious association is found between postoperative complication and surgical approaches.

Comparison of acquired immure deficiency syndrome-related knowledge and behavior between persons with and without human immunodeficiency virus- infection among young male students who have sex with men / 北京大学学报(医学版)

OBJECTIVE@#To understand the differences between young male students who have sex with men (MSM) with and without human immunodeficiency virus (HIV)-infection in acquired immure deficiency syndrome (AIDS)-related knowledge and behavior, and to provide a scientific reference to make targeted and effective measures in AIDS prevention.@*METHODS@#Using snow balling sampling combined with participants' referral, we conducted a questionnaire survey among 548 young MSM students (in whom there were both HIV-positive and HIV-negative) in Harbin, Tianjin, Xi'an, and Chongqing cities from April 2017 to March 2018. The chi-square test and binary Logistic regression were used to compare the differences in AIDS-related knowledge and behavior between males with and without HIV-infection.@*RESULTS@#A total of 583 questionnaires were obtained, of which 548 were valid, with an effective rate of 94.0%. Having a junior college education or below (P=0.002), a monthly consumption level of less than 2 000 RMB (P=0.021), and living off campus (P=0.004) were associated with being tested positive for HIV. In any period of schooling, receiving AIDS prevention education was a protective factor for HIV infection [Primary school OR=0.203 (0.073－0.561), junior high school OR=0.287 (0.142－0.581), senior high school OR=0.271 (0.142－0.518), and university OR=0.322 (0.168－0.616)]. There was no statistical difference between HIV positive and negative young MSM students in the cognition of "AIDS-related Knowledge for Public"(P=0.907) and "AIDS-related Knowledge for Youth"(P=0.782), with the awareness rate all about 90%. There was a statistical difference in the need for some specific knowledge (For "AIDS prevention and treatment policy", P=0.012, for "Ways to identify and prevent high-risk sexual behavior", P < 0.001). HIV-positive males had a younger age of first sexual activity (P=0.006), had more sexual partners in the early (P < 0.001) and had lower frequency of condom use (P < 0.001). However, there was no statistical difference in the later number of sexual partners (P=0.247) and the frequency of condom use (For regular sex partners, P=0.735, and for casual sex partners, P=0.765), which might be related to the change of sexual behavior characteristics caused by HIV infection (For regular sex partners, P < 0.001, and for casual sex partners, P=0.006).@*CONCLUSION@#There was no statistical difference between HIV positive and negative young MSM students in the cognition of "AIDS-related Knowledge for Public" and "AIDS-related Knowledge for Youth", which were both lower than 95% required by the state. However, the specificity in the knowledge needs was certainly shown. There was no significant difference in the recent sexual behavior between the two groups, but HIV positive students were more likely to have high-risk sexual behaviors in the early stage, so we should strengthen and move forward the sex education and AIDS prevention education with adjusted contents, and prevent high-risk sexual behaviors within young MSM students in the early stage.