基于真实世界数据探讨中医药治疗糖尿病肾病用药规律的研究＊

目的 基于临床信息系统分析总结真实世界的数据，采用数据挖掘的方法探讨中医药治疗糖尿病肾病的用药规律。方法 收集2018年1月-2020年12月上海中医药大学附属曙光医院宝山分院健康信息系统确诊的糖尿病肾病的门诊或住院患者的诊疗信息，建立Excel数据库，采用Excel 2010软件统计高频药物的四气、五味、归经及功效；使用SPSS Modeler 18.0软件中的Apriori算法分析关联规则，采用web节点建构药对关联网状图；运用SPSS 25统计软件进行因子分析。结果 本研究最终纳入477例接受中药饮片治疗的DKD患者，在1203条方剂信息中，涉及中药462种；使用频数排名前5位的中药分别是黄芪、黄精、石斛、山茱萸、麦冬；使用频数前5类的中药类别分别是补气药、补阴药、清热燥湿药、活血调经药、息风止痉药；在30味高频药物中，苦、甘、辛药味最为常见；药性寒、温数量接近；归脾经、肝经、肺经、肾经居多；关联规则提示，药物组合中置信度最高的组合为地龙-当归-僵蚕，因子分析共得到5个有效因子，累积贡献率为47.33%。结论 中医药治疗DKD在补益气血阴阳的同时，兼顾对瘀血、湿邪和痰饮的治疗，结合证型，可考虑使用黄芪、黄精、石斛、山茱萸、麦冬、金蝉花等药物的使用，清热燥湿药物如黄连、黄芩、黄柏可适当加入，为使邪有去处，大黄、车前子或可增添疗效。     

Epizootic features and control measures for lumpy skin disease in south‐east Serbia in 2016

Lumpy skin disease (LSD) is an infectious disease of cattle caused by virus of the Capripoxvirus genus (LSDV), family Poxviridae. Until 2015, it had not appeared in the Balkans. In June 2016, LSD spread throughout Serbia. This study analyses the first LSD occurrence, epizootic features, applied diagnostic procedures and control measures in five districts in south‐east Serbia (Pcinja, Jablanica, Pirot, Toplica and Nisava). In total, there were 225 LSD outbreaks reported in Serbia, out of which 189 (84%) were located in the study area. The highest number of outbreaks was registered in Pcinja district (169), where LSD was first registered. The median distance and time between the nearest previous outbreak sites were calculated (4.32 km and 9 days). The median altitude of outbreak locations was 992 m with more than 90% above 500 m (p ≤ 0.001). The average herd morbidity rate in the study area was 13.6% and the herd mortality rate was recorded only in Pcinja (0.5%) and Jablanica (1.6%) districts. Samples taken from the cattle suspected to LSD were subjected to real time PCR analysis. Out of 233 samples tested for LSDV 132 (56.7%) were positive. The LSDV genome was identified in skin nodules (85.4%), blood (72.7%) and nasal swabs (62.5%). Phylogenetic analysis indicated that the LSDV strain circulating in Serbia fell within the cluster of field LSDV found worldwide. In response to the LSD epizootic, animal trade and movement were prohibited, complete stamping out, disinfection, disinsection and an entire bovine population vaccination using the homologous Neethling live attenuated vaccine (OBP, South Africa) were conducted. A month and a half after the completion of the vaccination campaign, the LSD epizootic was stopped, and no new cases have been reported since.     

A DNA vaccine expressing an optimized secreted FAPα induces enhanced anti-tumor activity by altering the tumor microenvironment in a murine model of breast cancer

Cancer-associated fibroblasts (CAFs), major components of the tumor microenvironment (TME), promote tumor growth and metastasis and inhibit the anti-tumor immune response. We previously constructed a DNA vaccine expressing human FAPα, which is highly expressed by CAFs, to target these cells in the TME, and observed limited anti-tumor effects in the 4T1 breast cancer model. When the treatment time was delayed until tumor nodes formed, the anti-tumor effect of the vaccine completely disappeared. In this study, to improve the safety and efficacy, we constructed a new FAPα-targeted vaccine containing only the extracellular domain of human FAPα with a tissue plasminogen activator signal sequence for enhanced antigen secretion and immunogenicity. The number of CAFs was more effectively reduced by CD8⁺ T cells induced by the new vaccine. This resulted in decreases in CCL2 and CXCL12 expression, leading to a significant decrease in the ratio of myeloid-derived suppressor cells in the TME. Moreover, when mice were treated after the establishment of tumors, the vaccine could still delay tumor growth. To facilitate the future application of the vaccine in clinical trials, we further optimized the gene codons and reduced the homology between the vaccine and the original sequence, which may be convenient for evaluating the vaccine distribution in the human body. These results indicated that the new FAPα-targeted vaccine expressing an optimized secreted human FAPα induced enhanced anti-tumor activity by reducing the number of FAPα⁺ CAFs and enhancing the recruitment of effector T cells in the 4T1 tumor model mice.     

Efficacy and safety of nivolumab in patients with non-small cell lung cancer: a retrospective study in clinical practice

Nivolumab, a fully human immunoglobulin monoclonal antibody inhibiting the programmed cell death protein‐1 receptor, demonstrated robust efficacy and a manageable safety profile across multiple tumor types in clinical trials. The aim of the present study was to investigate the efficacy and safety of nivolumab for pretreated patients with non-small cell lung cancers in clinical practice. In this observational monocentric retrospective study, 98 patients were enrolled between February 2015 and February 2016. The global median overall survival was 6.34 months (95% confidence interval (CI) : 4.11–10.88) and the global median progression free survival was 1.84 months (95% CI: 1.68–2.73). In the univariate analysis, clinical performance status score was the only factor significantly correlated with overall survival. The safety profile of nivolumab is consistent with that described in prior studies, with only 7% undesirable effects requiring the discontinuation of treatment. The results of the present study demonstrate that nivolumab affords clinical efficacy and manageable tolerability in patients with non-small cell lung cancers.     

T-DM1 Efficacy in Patients With HER2-positive Metastatic Breast Cancer Progressing After a Taxane Plus Pertuzumab and Trastuzumab: An Italian Multicenter Observational Study

BackgroundT-DM1 improves progression-free survival (PFS) and overall survival (OS) in patients with metastatic human epidermal growth factor receptor 2-positive (HER2⁺) breast cancer progressing on prior trastuzumab plus a taxane. A paucity of data is available on T-DM1 efficacy after dual anti-HER2 blockade with pertuzumab and trastuzumab plus a taxane, which represents the current first-line standard of care. The present study is a retrospective/prospective evaluation of the efficacy and activity of second-line T-DM1 after front-line pertuzumab-based therapy.Patients and MethodsEligible patients were identified within the Gruppo Italiano Mammella (GIM) 14/BIOMETA study, a retrospective/prospective multicenter study on treatment patterns and outcomes of patients with metastatic breast cancer (ClinicalTrials.gov Identifier: NCT02284581). We searched for patients who received second-line T-DM1 after taxane plus trastuzumab and pertuzumab between November 15, 2013 and May 31, 2018. We calculated median PFS, median time to treatment failure (TTF), prolonged duration of therapy (PDT), objective response rate (ORR), and 1-year OS.ResultsOf 445 patients with HER2⁺ metastatic breast cancer, 77 were eligible for the analysis. At a median follow-up of 7 months, median PFS was 6.3 months (95% confidence intervals [CI], 4.8-7.7 months), and median TTF was 6.2 months (95% CI, 4-8.6 months). More than one-third of patients (37.6%; n = 29) experienced PDT with an ORR of 27.1%. At data cutoff, the median OS was not reached, and the 1-year OS was 82%.ConclusionsOur results show meaningful activity of T-DM1 after front-line pertuzumab plus trastuzumab and a taxane, with about 27% of patients having an objective response and 40% of patients achieving durable disease control.     

虚实结合的翻转课堂在解剖实验教学中的应用

目的评价虚实相结合的翻转课堂在系统解剖学实验教学中的应用。方法选取齐齐哈尔医学院2018级临床专业和医学影像学专业学生共107名,在系统解剖学实验课中,对某些章节采用部分翻转课堂的教学模式,对照章节则采用传统的教学方法。教学结束后进行考核,比较前后章节的课堂测验成绩,另外采用调查问卷,分析学生对两种教学方法的满意度。结果临床医学和医学影像学专业的学生第二次课堂测试的成绩均高于第一次课堂测试的成绩(P <0.01),同时学生对翻转课堂教学模式的满意度高于传统教学法。结论在系统解剖学实验教学中实行翻转课堂教学模式,同时讲解实物标本并应用数字人解剖学系统进行知识内化,不仅能提高学生的学习成绩,也能调动学生学习系统解剖学的热情,增加教学效果满意度,并为其他解剖学专业课的教学模式改革提供参考和借鉴。     

Quality and denoising in real‐time functional magnetic resonance imaging neurofeedback: A methods review

Neurofeedback training using real‐time functional magnetic resonance imaging (rtfMRI‐NF) allows subjects voluntary control of localised and distributed brain activity. It has sparked increased interest as a promising non‐invasive treatment option in neuropsychiatric and neurocognitive disorders, although its efficacy and clinical significance are yet to be determined. In this work, we present the first extensive review of acquisition, processing and quality control methods available to improve the quality of the neurofeedback signal. Furthermore, we investigate the state of denoising and quality control practices in 128 recently published rtfMRI‐NF studies. We found: (a) that less than a third of the studies reported implementing standard real‐time fMRI denoising steps, (b) significant room for improvement with regards to methods reporting and (c) the need for methodological studies quantifying and comparing the contribution of denoising steps to the neurofeedback signal quality. Advances in rtfMRI‐NF research depend on reproducibility of methods and results. Notably, a systematic effort is needed to build up evidence that disentangles the various mechanisms influencing neurofeedback effects. To this end, we recommend that future rtfMRI‐NF studies: (a) report implementation of a set of standard real‐time fMRI denoising steps according to a proposed COBIDAS‐style checklist ( https://osf.io/kjwhf/ ), (b) ensure the quality of the neurofeedback signal by calculating and reporting community‐informed quality metrics and applying offline control checks and (c) strive to adopt transparent principles in the form of methods and data sharing and support of open‐source rtfMRI‐NF software. Code and data for reproducibility, as well as an interactive environment to explore the study data, can be accessed at https://github.com/jsheunis/quality‐and‐denoising‐in‐rtfmri‐nf.     

Immunotherapy choice and maintenance for generalized myasthenia gravis in China

AimsTo compare long‐term efficacy and safety of immunotherapeutic strategies as maintenance to prevent disease relapses of generalized myasthenia gravis (MG) in real‐world settings.MethodsThis is a retrospective cohort study on generalized MG conducted in seven major neurological centers across China. Eligible participants were patients with generalized MG who were under minimal manifestation status or better. Main outcome measures were probability of patients free of relapses and causes of drug discontinuation.ResultsAmong 1064 patients enrolled, the median (interquartile range) age was 50.3 (37.0‐62.5) years and 641 (60.2%) were women. Disease relapse was significantly lower for rituximab (6.1%) compared with all the other monotherapies (hazard ratio [HR] = 0.18, 95% confidence interval [CI] 0.06 to 0.56, P = .0030). As combination therapies, tacrolimus in combination with corticosteroids reduced risk of disease relapses compared with azathioprine with corticosteroids (HR = 0.45, 95% CI 0.25 to 0.81, P = .0077) or mycophenolate mofetil with corticosteroids (HR = 0.32, 95% CI 0.15 to 0.67, P = .0020). Otherwise, lower‐dose corticosteroids or azathioprine as monotherapy significantly increased risk of disease relapses (HR = 2.78, 95% CI 1.94 to 3.99, P < .0001; HR = 2.14, 95% CI 1.42 to 3.23, P = .0003, respectively). The proportion of discontinuation was lowest in patients with rituximab (20.4%) as monotherapy and tacrolimus with corticosteroids (23.6%). Overall, combination treatment of immunosuppressants with corticosteroids had a lower rate of discontinuation compared with corresponding monotherapy (HR = 0.51, 95% CI 0.36 to 0.71, P < .0001).ConclusionsRituximab as monotherapy and tacrolimus with corticosteroids displayed better clinical efficacy as well as drug maintenance to prevent disease relapses in patients with generalized MG.