To develop a prognostic model for neoadjuvant immunochemotherapy efficacy in esophageal squamous cell carcinoma by analyzing the immune microenvironment.

Objective: The choice of neoadjuvant therapy for esophageal squamous cell carcinoma (ESCC) is controversial. This study aims to provide a basis for clinical treatment selection by establishing a predictive model for the efficacy of neoadjuvant immunochemotherapy (NICT). Methods: A retrospective analysis of 30 patients was conducted, divided into Response and Non-response groups based on whether they achieved major pathological remission (MPR). Differences in genes and immune microenvironment between the two groups were analyzed through next-generation sequencing (NGS) and multiplex immunofluorescence (mIF). Variables most closely related to therapeutic efficacy were selected through LASSO regression and ROC curves to establish a predictive model. An additional 48 patients were prospectively collected as a validation set to verify the model's effectiveness. Results: NGS suggested seven differential genes (ATM, ATR, BIVM-ERCC5, MAP3K1, PRG, RBM10, and TSHR) between the two groups (P < 0.05). mIF indicated significant differences in the quantity and location of CD3+, PD-L1+, CD3+PD-L1+, CD4+PD-1+, CD4+LAG-3+, CD8+LAG-3+, LAG-3+ between the two groups before treatment (P < 0.05). Dynamic mIF analysis also indicated that CD3+, CD8+, and CD20+ all increased after treatment in both groups, with a more significant increase in CD8+ and CD20+ in the Response group (P < 0.05), and a more significant decrease in PD-L1+ (P < 0.05). The three variables most closely related to therapeutic efficacy were selected through LASSO regression and ROC curves: Tumor area PD-L1+ (AUC= 0.881), CD3+PD-L1+ (AUC= 0.833), and CD3+ (AUC= 0.826), and a predictive model was established. The model showed high performance in both the training set (AUC= 0.938) and the validation set (AUC= 0.832). Compared to the traditional CPS scoring criteria, the model showed significant improvements in accuracy (83.3% vs 70.8%), sensitivity (0.625 vs 0.312), and specificity (0.937 vs 0.906). Conclusion: NICT treatment may exert anti-tumor effects by enriching immune cells and activating exhausted T cells. Tumor area CD3+, PD-L1+, and CD3+PD-L1+ are closely related to therapeutic efficacy. The model containing these three variables can accurately predict treatment outcomes, providing a reliable basis for the selection of neoadjuvant treatment plans.

Prognostic significance of positive lymph node regression grade to neoadjuvant chemoradiation for esophageal squamous cell carcinoma.

BACKGROUND AND PURPOSE: To assess the relationship between metastatic lymph node (LN) responder status and recurrence-free survival (RFS) in patients undergoing neoadjuvant chemoradiotherapy (NCRT). MATERIALS AND METHODS: We retrospectively reviewed 304 patients with local advanced esophageal squamous cell carcinoma received NCRT followed by esophagectomy. For 112 patients with positive node, according to the proportion of residual viable tumor cells area within the whole tumor beds of all metastatic LNs, we classified LN-tumor regression grade (LN-TRG) into four categories: grade 1, 0%; 2, <10%; 3, 10%-50%; 4, >50%. Patients with grade 1-2 LN-TRG of were considered LN responders, and those with grades 3-4, as LN nonresponders. Univariate and multivariate analyses of RFS were estimated by a Cox regression model, Kaplan-Meier curve, and log-rank test. RESULTS: The median follow-up time of a total of 112 patients was 29.6 months. Fifty-two (46.4%) patients have experienced recurrence. In Cox univariate analysis, differentiation, AJCC stage LN responder status, nerve invasion, and lymphovascular invasion significantly correlated with RFS. Multivariate analysis for RFS revealed that LN responder status and AJCC stage (p < 0.05) were independent prognostic factor. The 3-year RFS rates for patients with LN-TRG of 1-4 grades were 72.7%, 76.5%, 37.4%, and 28.5%, respectively, and the median RFS times were not reach, 43.56, 28.09, and 22.77, respectively. CONCLUSIONS: LN responder status is an independent prognostic factor for RFS in esophageal cancer patients who received NCRT.

The value of pre-pregnancy BMI, gestational maximum fasting blood glucose and weight gain during pregnancy to evaluate fetal macrosomia after 28 weeks of gestational diabetes mellitus / 中国医师杂志

Objective:To analyze the relationship between pre-pregnancy body mass index (BMI), gestational random fasting glucose maximum, weight gain during pregnancy, and the occurrence of macrosomia in pregnant women diagnosed with gestational diabetes after 28 weeks gestation.Methods:The clinical data of 310 pregnant women with gestational diabetes after 28 weeks of diagnosis in Xuanwu Hospital of Capital Medical University in 2014 were retrospectively analyzed. They were divided into observation group (96 cases) with macrosomia and control group (214 cases) with normal birth weight according to the weight of newborn. The differences of BMI before pregnancy, the highest value of fasting blood glucose during pregnancy and weight gain during pregnancy between the two groups were analyzed.Results:The pre-pregnancy BMI , the highest value of random fasting blood glucose and weight gain during pregnancy in macrosomia group were significantly higher than those in non macrosomia group ( P<0.05); And the best cut-off point for predicting the delivery of macrosomia in pregnant women with gestational diabetes after 28 weeks of pregnancy was 22.077 kg/m 2, 4.965 mmol/L and 17.400 kg, respectively. The area under the curve (AUC) was 0.646, 0.595 and 0.699 respectively. After correction of confounding factors, the BMI ( OR=1.238, 95% CI: 1.132, 1.354, P<0.001) and weight gain during pregnancy ( OR=1.189, 95% CI: 1.120, 1.262, P<0.001) were risk factors for macrosomia in gestational diabetes mellitus after 28 weeks of gestation ( P<0.05). Conclusions:Pre-pregnancy BMI>22.077 kg/m 2, gestational maximum fasting blood glucose >4.965 mmol/L and gestational weight gain >17.400 kg were all high risk factors for gestational diabetes mellitus pregnant women after 28 weeks. For pregnant women with gestational diabetes, active prenatal intervention and health management are of great significance in reducing the risk of macrosomia.

Systematic Review of Methodological Guidelines for Health Technology Assessment at Home and Abroad / 中国药房

OBJECTIVE：To evaluate guidelines f or health technology assessment （HTA）at home and abroad ，and to provide reference for scientific formulation of HTA guidelines in China. METHODS ：Databases including PubMed ，Embase，Guidenlines International Network and 83 official websites from 26 countries governments and academic organizations were searched to collect HTA guidelines from inception to April 2020. Two reviewers independently screened literature and extracted data ，including basic characteristics， content of guideline and assessment content. Then a descriptive analysis was conducted. RESULTS & CONCLUSIONS：A total of 19 guidelines published during 2001 to 2018 were included ，7 guidelines（36.8％）were published in 2015-2020；in addition to 1 guideline from WHO ，14 guidelines （73.7％）were published in Europeand ，2 guidelines（10.5％） in North America and 1 guideline each from South America and Asia （5.3％）. There were 11 guidelines（57.9％）developed by academic organizations and 8 guidelines（42.1％）by health administration ；11 guidelines（57.9％）were evidence-based ，while the others weren ’t evidence- based （42.1％）. The purpose ，content and object of assessment are demonstrated in 19 guidelines；18 guidelines specified the assessment method （94.7％），and 16 guidelines（84.2％）defined the subject of assessment ；14 guidelines （73.7％）specified the HTA assessment process ；12 guidelines（63.3％）mentioned the conflict of interest in HTA assessment process；7 guidelines（36.8％）mentioned the application of assessment results. There are some differences in the formulation methods and contents of HTA guidelines in foreign countries ，but the core contents ar e basically the same. At present ，there is a lack of HTA guidelines in China. We can refer to foreign guidelines，and establish applicable HTA guidelines which aresuitable for national conditions ，so as to provide scientific guidance for HTA research.

Anti-TNF-α Monoclonal Antibody for Ulcerative Colitis：Methodology/Reporting Quality Reevaluation of Meta-analysis/ Systematic Evaluation / 中国药房

OBJECTIVE： To conduct methodology/reporting quality reevaluation for Meta-analysis/systematic evaluation of anti-TNF-α monoclonal antibody in the treatment of ulcerative colitis. METHODS： Retrieved from the Cochrane library， PubMed， Embase， CBM， Wanfang database and CNKI during data base establishment to Nov. 2018， Meta-analysis/systematic evaluations of anti-TNF-αmonoclonal antibody in the treatment of ulcerative colitis were collected. After data extraction of literatures that meet the inclusion criteria， methodological quality and reporting quality of included studies were evaluated by using AMSTAR scale and the PRISMA statement. RESULTS： Fourteen literatures of Meta-analysis/systematic evaluation were included. The average score of AMSTAR methodology quality （full score of 11 points） was 6.89， with medium methodological quality. PRISMA score （full score of 27 points） ranged from 15 to 26.5. CONCLUSIONS： Meta-analysis/systematic evaluations of anti-TNF-α monoclonal antibody for ulcerative colitis have poor methodological and reporting quality.

Efficacy and Safety of Clonidine Transdermal Patch for Child Tic Disorders ：A Meta-analysis / 中国药房

OBJECTIVE： To systematically evaluate the efficacy and safety of Clonidine tansdermal patch for child tic disorders in children， and to provide evidence-based reference for clinical treatment. METHODS： Retrieved from Medline， Embase， Cochrane library， CNKI， VIP， CBM and Wanfang database， randomized controlled trials （RCTs） about Clonidine tansdermal patch （trial group） versus other therapies （control group， including placebo group， thiopride group， haloperidol group） for child tic disorders were collected from datbase estallishment to July 2018. The literatures met inclusion criteria were summarized. After quality evaluation with Cochrane system evaluation manual 5.1.0， Meta-analysis of reduction rate （amount） of YGTSS， the incidence of ADR and response rate was performed by using Rev Man 5.3 statistical software. Descriptive analysis was performed on indicators of groups that were unable to perform Meta-analysis. RESULTS： A total of 8 RCTs involving 1 320 patients were included. Among them， 2 RCTs involved placebo in control group； 2 RCTs involved thiopride， 3 RCTs involved haloperidol， and 1 RCT involved thiopride and haloperidol. Results of Meta-analysis showed that reduction rate of YGTSS in trial group were significantly higher than haloperidol group [MD＝21.94， 95％CI（21.03， 22.86）， P＜0.001]， but there was no statistical significance compared with thiopride group [MD＝10.66， 95％CI（－15.68， 37.00）， P＝0.43]. The incidence of adverse events （mainly including skin itching， redness， dry mouth， dizziness， decreased blood pressure， abnormal electrocardiogram） in trial group were significantly lower than thiopride group [OR＝0.42， 95％CI（0.22， 0.82）， P＝0.01] and haloperidol group [OR＝0.17， 95％CI（0.09， 0.32）， P＜0.001]， but there was no statistical significance compared with placebo group [OR＝0.61， 95％CI（0.29， 1.29）， P＝0.20]. There was no statistical significance in response rate of trial group compared with thiopride group [OR＝1.29，95％CI（0.38， 4.39）， P＝0.69] and haloperidol group [OR＝1.63， 95％CI（0.89， 2.96）， P＝0.11]. The results of descriptive analysis showed that reduction rate （amount） of YGTSS in trial group was significantly higher than that of placebo group （P＜0.05）， and response rate of trial group was significantly higher than that of placebo group （P＜0.01）. CONCLUSIONS： For child tic disorders in children， Clonidine tansdermal patch is better than placebo and haloperidol in reduction rate （amount） of YGTSS， and is similar to thiopride. Response rate of Clonidine tansdermal patch is better than that of placebo， and is similar to those of thiopride and haloperidol. The safety of Clonidine tansdermal patch is better than those of thiopride and haloperidol， and is similar to that of placebo.

Evidence-based Evaluation of Global Existed Diarrhea Guidelines of Children / 中国药房

OBJECTIVE:To evaluate the global existed diarrhea guidelines of children,and provide evidence and methodology reference for clinical practice and the formulation of diarrhea evidence-based guideline of children in China. METHODS:Retrieved from PubMed,Embase,CBM,CNKI,VIP,Wanfang databases and related websites,references included in studies were retrieved additionally from database building to Dec. 2017. The methodological quality of the guideline was evaluated by 2 researchers independently with guideline evaluation toolⅡ(AGREEⅡ). ICC analysis was used to calculate the differences between the evaluation results of 2 researchers and analyze the difference of the guidelines. RESULTS:A total of 1 168 literatures were collected primarily, and 15 guidelines were involved finally,among which 3 guidelines were from USA,2 from British,2 from WHO,each one from Italy,Europe,India,Australia,Malaysia,New South Wales,South Africa and China,respectively. Of 15 guidelines,there were 10 evidence-based guidelines and 5 non-evidence-based guidelines;evidence levels of guidelines and the method of recommendation intensity were different. ICC of 2 researchers were higher than 0.75(P<0.05),indicating good homogeneity among them. The quality of 15 guidelines were not high enough,and the scores of included guidelines in the field of AGREEⅡin descending order were as follows:scope and purpose(84.44%),clarity of presentation(79.82%),stakeholder involvement(45.74%), rigor of development(41.18%), editorial independence (36.39%)and applicability(33.89%). Main prevention and treatment method recommended by guideline included that(1) prevention and treatment of dehydration was the key link in the treatment of children's diarrhea;(2)guidelines generally believed continuous breastfeeding during rehydration could reduce the risk of dehydration in children;(3)zinc preparation was recommended to shorten the course of diarrhea;(4)antibiotics were used rationally, etc. CONCLUSIONS:The quality of global existed diarrhea guidelines of children should be improved. There is no comprehensive diarrhea evidence- based guideline of children in China,and there is a large discrepancy between the situation of pediatric diarrhea therapy in China and WHO standard;it is urgent to establish a standard treatment. It is suggested to formulate high quality pediatric diarrhea guideline in accordance with the national conditions of China,based on standards for international guideline report, comprehensively considering disease burden and characteristics of pediatric diarrhea in China.

Evidence-based Evaluation of Monitoring System for Global Short Drugs / 中国药房

OBJECTIVE:To systematically evaluate the monitoring system for global short drugs,and provide evidence-based reference and policy recommendations for developing the short drug monitoring in China. METHODS:Relevant literatures pub-lished in PubMed,Embase,CNKI,Wanfang,VIP database from building to Apr. 3rd in 2017 were retrieved by using"Drugs (cheap drugs,essential medicines,emergency drugs) storage""Short drugs""Insufficient supply of drugs""Drug shortage"as Chinese keywords,and"Drug storage""Out-of-stock drug""Stortage of medicine""Stock out of medicine"as English keywords. Literatures about monitoring system for short drugs in Baidu,Google and national or regional health administration websites were collected,and general information,data collection,data validation,data reporting method,feedback and improvement measures of monitoring system were extracted. RESULTS & CONCLUSIONS:Totally 25 literatures were included,20 national or regional health administration websites were retrieved. 11 countries and European Union had established monitoring system for short drugs. The main reporting agencies in each country were different,which were production enterprises,business enterprises and medical in-stitutions. It was mainly reported by network. Data validation was mainly conducted by specialized departments or groups for short drugs in each country. The monitoring reporting included information of short drugs and discontinued drugs. Countermeasures in each country mainly included looking for alternative drugs,encouraging production,temporary import,looking for new or other sources of raw materials and speeding up the approval of short drugs. Besides, precautions included implementation relevant laws and guidelines for short drugs,and increasing the cooper-ation with non-government departments,etc. Monitoring sys-tem for short drugs needs to be further improved in China. Itis suggested to establish monitoring and early warning platform for short drugs,and hierarchical intervention mechanism,improv-ing relevant laws and developing guidelines on managing short drugs.