癌相关成纤维细胞在乳腺癌侵袭转移及耐药中的作用研究进展

癌相关成纤维细胞(CAF)是肿瘤微环境中主要的基质细胞。CAF可在血小板源性生生长因子、成纤维细胞生长因子、白介素6及肝细胞生长因子等多种分泌因子作用下由正常成纤维细胞转化形成,也可由间充质干细胞、脂肪细胞等多种细胞可通过上皮间质转化(EMT)过程形成,还有部分由癌症干细胞转化而来。近来有研究显示,乳腺癌中的CAF可通过分泌多种细胞因子及外泌体、参与EMT及细胞外基质重塑,进而促进乳腺癌细胞侵袭转移,也可在肿瘤缺氧微环境下通过激活相关信号通路促进乳腺癌细胞生长和侵袭。此外,CAF通过增加了乳腺癌细胞的凋亡阈值、作为抗肿瘤药物的物理屏障、分泌的谷氨酰胺增加乳腺癌细胞的存活率、激活生长因子相关的信号通路或增加线粒体功能产生抗凋亡作用等多种途径介导乳腺癌化疗耐药、内分泌治疗耐药及多药耐药。笔者总结CAF的重要来源及其在乳腺癌侵袭转移与治疗耐药中的研究进展。     

肝阴虚证证候特点及辨证用药规律的文献研究

目的:为进一步深入研究和探讨肝阴虚证候的本质,本文分析和整理肝阴虚证的病因病机、证候表征、证候属性疾病及遣方选药的规律。方法:运用检索文献并进行频数统计的方法,检索查阅1960年9月1日至2019年1月10日中国知网中医临床研究文献。结果:肝阴虚证的病因病机为肝失疏泄,气机郁滞,化火伤阴,阴液亏虚,失于濡养;证候辨证要点主要为脉弦细数,舌红少津,头晕目眩,五心烦热,口咽干燥,两目干涩;证候临床属性疾病有肝炎、肝硬化、肝纤维化、肝癌;临床上治疗肝阴虚证使用处方主要为一贯煎、补肝汤、四物汤、芍药甘草汤,临床高频使用中药为生地黄、白芍、枸杞、当归、麦冬。结论:本文对于肝阴虚证的证候特点以及辨证用药规律做出系统的总结与归纳,将有关肝阴虚证的论述联系起来,形成统一的整体,为揭示肝阴虚证的本质与临床上形成较为成熟的肝阴虚证治疗方案提供参考。     

A prognostic signature based on immune-related genes for cervical squamous cell carcinoma and endocervical adenocarcinoma

Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) is the fourth commonest female malignancy worldwide. CESC progresses in immune-microenvironment mainly composed of infiltrating immune and stromal cells. Here, we performed an integrated analysis incorporating the expression profiles from the Cancer Genome Atlas (TCGA) database and scores of immune and stromal cells calculated by Estimation of Stromal and Immune cells in Malignant Tumours using Expression data (ESTIMATE) algorithm. A two-gene signature (CD1C and CD6 genes) was established to predict the prognosis of CESC. Based on this signature, patients were divided into the high- and low-risk groups, and this signature showed good prognostic performance according to the results of Kaplan-Meier analysis and receiver operating characteristic (ROC) analysis in train set and two validation sets. A nomogram was built for evaluating the clinical applicability of this signature. In addition, based on Tumor Immune Estimation Resource (TIMER) database, 2 hub genes showed negative correlations with tumor purity and positive correlations with infiltrating levels of immune filtrating cells. What’s more, we propose new treatment strategies for the two prognostic subtypes. Low- risk patients were found presenting with a higher level of immune checkpoint molecules and showing higher immunogenicity in immunophenoscore (IPS) analysis, which indicated a better response for immunotherapy. Meanwhile, estimated by Genomics of Drug Sensitivity in Cancer (GDSC) database, the high-risk patients showed sensitive responses to five chemotherapy drugs. Finally, 10 candidate small-molecule drugs for CESC were defined. In summary, the CD1C-CD6 signature can accurately predict the prognosis of CESC.     

Enhanced normograms and pregnancy outcome analysis in nonhuman primate developmental toxicity studies

The incidence of spontaneous pregnancy/infant losses is highly variable in long-tailed macaques (cynomolgus monkey), making it potentially difficult to ascertain test item-related effects in developmental toxicity studies. Therefore, pregnancy normograms had been developed by Jarvis et al. [1] to aid in the distinction of normal (e.g. test facility background) versus non-normal pregnancy outcomes. These normograms were mostly derived from embryo-fetal development studies and from PPND studies with a postnatal phase limited to seven days. However, the enhanced pre- and postnatal developmental (ePPND) study paradigm has essentially replaced these former study types. This work aims at providing enhanced normograms (e-normograms) in the context of regulatory ePPND studies. Survival functions for the prenatal phase (286 control pregnancies) and the postnatal phase (222 live infants) were estimated using the Kaplan-Meier estimator. Normograms were generated from survival curves and pseudo-study simulations. Data were available from two test facilities with comparable EU-compliant animal husbandry. Pregnancy duration/outcome as well as survival functions did not differ significantly between test facilities indicating that this husbandry system yields comparable developmental observations across different test facilities, at least in this NHP species. These novel e-normograms were developed for pregnant long-tailed macaques and provide an extended postnatal period up to three months, a new concept of separate normograms for the prenatal and the postnatal period, specific information on the perinatal phase events, a prediction of expected number of live infants for group size management, and the option to evaluate effects on pregnancy duration through distinction of live births and infant losses.     

英国价值定价理念对我国医保药品报销政策的启示

本文在梳理英国医保药品报销政策的基础上,通过对价值定价理念的深入研究和理解,系统探讨其在报销政策制定过程中对药品目录遴选、价值测算、支付标准确定、医保基金平衡和报销效益评估的作用机制,并深入思考通过价值定价理念建立起的药物警戒体系与药品报销政策间的衔接机制。在此基础上总结价值定价理念的特点、应用阶段和具体操作方法,以期为我国提供借鉴。     

Relationship between using cell phone and the risk of accident with motor vehicles: An analytical cross-sectional study

Purpose: Traffic accidents are one of the major health problems in the world, being the first cause of burden of illness and the second leading cause of death in Iran. The Sistan-Baluchestan province is one of the most accidental provinces of Iran with the highest rate of accidents-caused deaths. This study was conducted to determine the risk factors associated with traffic accidents in Zahedan through 2013 to 2016. Methods: This analytical cross-sectional study was carried out on 223 drivers from Zahedan who were traumatized by traffic accident and sent to Zahedan hospitals. The data were obtained through interviews taken by the trained interviewers via refereeing to the medical records and collected in the researcher-made checklist. Census was obtained from the study subjects. For data analysis, independent t-test, one-way ANOVA, Chi-square and logistic regression were used with the Stata software version 11.0. Results: In this study, 223 male subjects with the mean age of (32.54 ± 12.95) years, 39.8% single and 60.2% married, entered for investigation. Most accidents (38.8%) occurred between 12:00 to 17:59. While driving, 47.1% of the study subjects were using cell phones, 89.1% had manual use of mobile phones, 21.9% had a habit of sending short message service (SMS) and 23.4% had sent SMS within 10 min before the accident. The one way analysis of variance showed that the mean age of individuals with marital status, driving experience, education and accident with motorcycle were significantly different (p < 0.05). Also, the multivariate logistic regression test indicated a significant relationship of smoking, ethnicity, insurance and SMS typing while driving with motorcycle accident (p < 0.05). Conclusion: In this study, SMS and smoking while driving had the highest risk among the variables studied in the motorcycle accidents. Therefore, effective education attempting to enhance people''s awareness about the consequences of using cell phone and smoking during driving to reduce traffic accidents seems necessary.     

Osteoarthritis today: Lost in translation?

Osteoarthritis (OA) is a highly prevalent joint disease that is associated with pain, loss of function, and high direct and indirect economic costs. The current therapeutic options are inadequate, providing only a moderate symptom relief without the possibility of disease modification. While treatment options and personalized medicines are increasing for many complex diseases, OA drug development has been impeded by the advanced state of disease at the time of diagnosis and intervention, heterogeneity in both symptoms and rates of progression, and a lack of validated biomarkers and relevant outcome measures. This review article summarizes the OA landscape, including therapies in development as potential OA treatments, potential biomarkers undergoing evaluation by the US Food and Drug Administration, and a summary of current OA treatment guidelines, with a particular focus on the knee OA.     

Variation in the prescription drugs covered by health systems across high-income countries: A review of and recommendations for the academic literature

BackgroundBecause not all medicines are equally safe, effective, and affordable, health systems often use formularies to define explicitly which medicines will be included and excluded from coverage.ObjectiveWe sought to synthesize methods and findings from published studies of formulary variation across health systems in high-income countries.MethodsWe conducted a systematic review of peer-reviewed research papers published from 2000 to 2017, inclusively. Because of the heterogeneous nature of the literature, we used an inductive approach to summarize methods and findings.ResultsNine studies met our study inclusion criteria. Included studies used a variety of methods for selecting medicines for analysis, for measuring coverage levels, and for measuring concordance between formularies. Studies assessing variations in coverage of all licensed medicines and found lower rates of cross-national coverage variation than studies of coverage for selected specialty drugs and indications. The one study that focused on coverage of high-volume medicines found the most complete and consistent levels of formulary listings across countries.ConclusionAlthough published studies contain interesting findings that likely have prompted discussions about their policy implications, the literature can be improved with greater transparency concerning the overarching objective of work in this area and more rigor concerning the selection, analysis, and reporting of data.