穴位埋线配合针刺及康复训练治疗中风后肢体偏瘫的临床观察

目的观察穴位埋线配合针刺及康复训练治疗对中风后恢复期肢体偏瘫患者的临床治疗效。 方法选择2018年6月至2019年8月贵州省铜仁市碧江区中医院康复科收治住院的98例中风恢复期肢体偏瘫患者，按随机数值表法随机分为对照组48例(针刺联合康复训练治疗)和治疗组50例(穴位埋线配合针刺联合康复训练治疗)，连续治疗4周，治疗前和治疗后神经功能缺损程度评定量表(NDS)、Berg平衡功能进行评定量表(BBS)、巴氏(Barthe)指数组间比较采用两独立样本t检验，治疗前后比较采用自身配对t检验；2组总有效率比较采用χ²检验。 结果(1)总有效率：治疗组有效50例，无效0例，治疗总有效率100.0%(50/50)；对照组有效43例，无效5例，总有效率89.6%(43/48)，治疗组总有效率高于对照组(χ²＝12.163，P<0.05)。(2)2组治疗前后自身比较：治疗4周后，治疗组与对照组患者NDS评分均较治疗前降低(t＝18.39、16.22，均P<0.05)，治疗组治疗后Barthel指数、BBS评分均较治疗前评分增高(t＝145.00、54.25，均P<0.05)，对照组治疗后Barthel指数、BBS评分均较治疗前评分增高(t＝126.00、27.13，均P<0.05)，差异均有统计学意义。(3)治疗组与对照组比较：治疗4周后，治疗组患者NDS评分均较照组降低(t＝-5.299，P<0.05)，治疗组Barthel指数、BBS评分均较照组评分增高(t＝2.805、13.203，均P<0.05)。 结论埋线疗法结合针刺、康复训练对中风恢复期肢体偏瘫患者有良好治疗作用，能更好、更快地提高患者的运动功能和日常生活能力及生存的质量，此法值得临床推广。     

加兰他敏和石杉碱甲生物合成的研究进展

植物来源的加兰他敏、石杉碱甲等乙酰胆碱酯酶抑制剂(AChEIs)以其高效低毒的优势成为当前临床治疗阿尔茨海默病的主流药物。由于目前加兰他敏、石杉碱甲等AChEIs尚未实现工业规模化合成,故仍主要依赖植物提取。然而,药源植物培育周期长、难度大,药效物质含量低,随着社会需求的急剧攀升,供求矛盾日益突出。开发新替代资源以及利用现代基因工程技术合成加兰他敏、石杉碱甲等AChEIs是缓解当前矛盾的有效途径。对近年来加兰他敏和石杉碱甲生物合成的相关研究进展进行综述,总结了替代资源的开发研究现状,以期为挖掘加兰他敏、石杉碱甲等AChEIs优势新资源及利用代谢工程合成药效物质研究提供参考。     

山西营养与慢性病家庭队列人群体质指数与死亡率的关系

目的 分析山西营养与慢性病家庭队列人群BMI与总死亡率的关系。方法 以"2002年中国居民营养与健康状况调查"山西省调查人群为基线建立队列，于2015年12月至2016年3月对研究对象进行随访调查，对逝者进行死因回顾调查。2002年基线信息完整的≥ 18岁研究对象7 007人，随访到5 360人，随访率为76.5%。将研究对象按BMI分为8组，计算死亡率，以死亡率最低组作为参照，采用Cox比例风险回归模型估计全人群、分性别、年龄（≥ 60岁、<60岁）的各组死亡风险比（HR）及95% CI，模型调整基线年龄、性别、吸烟、饮酒、文化程度等因素，并进行敏感性分析。结果 共随访67 129人年，平均随访12.5年，死亡615人，队列总死亡率为916/10万人年。BMI为26.0~27.9 kg/m²组死亡率最低，以该组为参照组，多因素调整后，BMI<18.5、18.5~19.9、22.0~23.9和≥ 30.0 kg/m²组的死亡风险明显升高，调整HR值（95% CI）分别为1.90（1.26~2.86）、1.68（1.15~2.45）、1.49（1.08~2.06）和1.72（1.07~2.76）。对于≥ 60岁老年人，BMI<18.5 kg/m²组的死亡风险明显升高，调整HR值（95% CI）为1.94（1.20~3.15）。结论 BMI ≤ 19.9、22.0~23.9及≥ 30.0 kg/m²均会增加全因死亡风险。除关注肥胖外，低体重营养不良造成的老年人高死亡风险应特别引起重视。     

基于德尔菲法构建呼吸与危重症医学科住院医师规范化培训出科考核指标体系

目的　根据临床需求，结合医院实际，建立一套适应呼吸与重症医学科发展的科学、系统的出科考核评价体系。方法　采用文献分析法和德尔菲法，经过两轮咨询确定指标体系，采用优序图法确定指标权重。采用SPSS 22.0统计软件进行数据分析。结果　两轮咨询专家积极系数为100%和95.65%；两次咨询群体专家权威系数平均值为0.85；两轮专家咨询的协调系数分别为0.513、0.516；最终确立一级指标5项、二级指标14项。结论　专家积极程度和协调系数好，结果可信。确立的指标体系可用于医院呼吸与危重症医学科住院医师规范化培训考核评估。     

安罗替尼联合替吉奥治疗三线及以上晚期非小细胞肺癌的安全性和有效性

目的:前瞻性应用安罗替尼联合替吉奥治疗三线及以上晚期非小细胞肺癌，观察临床疗效和药物的安全性。方法:均经组织病理或细胞学明确诊断晚期非小细胞肺癌，且二线化疗治疗后疾病进展。口服安罗替尼胶囊8 mg/d，d1~14联合替吉奥胶囊60 mg/m2 bid d1~14，21天为一个周期。治疗终止时间为疾病进展或出现不可接受的毒副反应。结果:本研究结果显示，总体客观缓解率（ORR）可达到26.8%，总体疾病控制率（DCR）可达到80.5%，中位无进展生存期（mPFS）达到5.2个月（95%CI:3.9~6.6个月）。单因素分析，脑转移组患者mPFS（4.8个月）对比无脑转移组患者mPFS（5.9个月），两组差异具有统计学意义（P=0.039）。多变量回归分析显示，ECOG评分(P=0.002)、治疗线数（P=0.015）和疗效(P=0.014)是PFS的独立影响因素。最常见毒副反应为高血压、蛋白尿、骨髓抑制、胃肠道反应、疲乏和口腔黏膜炎。结论:安罗替尼联合替吉奥胶囊在晚期非小细胞肺癌三线及以上治疗中，其总体的疗效确切且药物毒副反应可控。     

Epidemiological and clinical comparisons of paediatric and adult sporotrichosis in Jilin Province,China

Sporotrichosis is endemic in Jilin Province of Northeast China. While paediatric cases make a substantial contribution to the epidemiological profile of sporotrichosis, the differences in the epidemiology and clinical manifestations of sporotrichosis between paediatric and adult patients remain unclear. We retrospectively reviewed the clinical records of 2968 cases of sporotrichosis (2113 adult patients aged ≥ 15 years and 855 paediatric patients aged < 15 years) over a nine-year period (01/01/2010-31/12/2018-). All the patients were diagnosed with sporotrichosis based on fungal culture of material from a skin lesion. In paediatric patients, the male:female ratio was 1.3:1, the incidence of sporotrichosis in the cold seasons was high (79.0%), most lesions occurred in the facial region (92.2%), and there was a preponderance of fixed cutaneous sporotrichosis (86.8%). In adult patients, the male:female ratio was 1:2.4, the incidence of sporotrichosis in the cold seasons was 66.0%, most lesions affected the extremities (48.6%) and the face (44.9%), and fixed cutaneous sporotrichosis was common (69.3%). The results indicate there were significant differences in the distribution of paediatric and adult sporotrichosis patients by sex, season with the highest occurrence of sporotrichosis, lesion sites and clinical types. Our results suggest that the epidemiology and clinical manifestations between paediatric and adult patients were different, and the route of infection of sporotrichosis in children may differ from that of adults in Jilin Province.     

Neoadjuvant Crizotinib in Resectable Locally Advanced Non–Small Cell Lung Cancer with ALK Rearrangement

Background

Locally advanced NSCLC is one of the most heterogeneous conditions, with multidimensional treatments involved. Neoadjuvant therapy had been commonly considered an optimal management strategy for patients with operable locally advanced. However, as targeted therapy has been widely applied in advanced NSCLC, neoadjuvant targeted therapy has remained poorly explored in locally advanced disease.

Different expression levels of exosomal miR-503 in peritoneal dialysis effluent from patients of different peritoneal transport characteristics and bioinformatics analysis

Objective To compare the expression level of exosomal miR-503 in peritoneal dialysis effluent (PDE) from patients of different peritoneal transport characteristics, predict the target genes of miR-503 and provide bioinformatic data for researches of peritoneal transport characteristics. Methods Twenty-four stable peritoneal dialysis (PD) patients were selected and divided into high transport group (H group, n=12) and low transport group (L group, n=12) according to the results of peritoneal equilibration tests (PET). The 500 ml PDE that was left on the patient's abdomen overnight was collected and concentrated using ultrafiltration cell. Exosomes in PDE were resuspended in phosphate buffered saline (PBS) after ultracentrifugation and the characteristics of PDE exosomes were identified by transmission electron microscope (TEM), nanoparticle tracking analysis (NTA), Western blotting and fluorescent staining. MicroRNAs were extracted from PDE exosomes. The expression levels of PDE exosomal miR-503 in the two groups were detected by quantitative real-time PCR. Then the relations between the relative quantity of PDE exosomal miR-503 and PET values or 24 h ultrafiltration volume (UF) were analyzed. Targetscan and miRDB databases were used to predict the target genes of miR-503. Gene ontology (GO) functional enrichment and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway analysis were relied on DAVID (https://david.ncifcrf.gov/). Results The exosomes in PDE showed a round and cup-shaped morphology under TEM, and the diameters were approximately 100 nm measured by NTA. The specific biomarkers of exosomes, CD63, CD81 and heat shock protein -70 (HSP-70) were all detected by Western blotting. The internalization and uptake of the exosomes was observed after fluorescent staining. The relative expression level of PDE exosomal miR-503 in H group was found to be significantly higher than that in L group (P=0.002), and the relative quantity of PDE exosomal miR-503 was significantly positively correlated with PET values (r=0.547, P=0.006), but not 24 h UF (r=-0.297, P=0.159). There were 156 target genes of miR-503 in total that could be predicted by two different databases at the same time. GO analysis of these 156 target genes was mainly focused on kinase binding, regulation of protein modification and catabolic process as well as regulation of epithelial cell proliferation. KEGG enriched many tumor associated or classical signaling pathways, including transforming growth factor-β (TGF-β) signaling pathway and vascular endothelial growth factor (VEGF) signaling pathway. The prediction showed that vascular endothelial growth factor A (VEGFA) was a direct target gene of miR-503 and it was also related to many proteins involved in fibrosis mechanism. Conclusions The expression level of PDE exosomal miR-503 is significantly higher in H group, and positively correlates with PET values, which may regulate the angiogenesis of peritoneal vessels by targeting VEGFA.     

Tao Liu research group of Peking University School of Pharmaceutical Sciences and Mo Li research group of Peking University Third Hospital joint developed CRISPR non-natural amino acid coupling technique to improve the efficiency of precise genome editing

Tao Liu research group of Peking University School of Pharmaceutical Sciences and Mo Li research group of Peking University Third Hospital joint developed CRISPR non-natural amino acid coupling technique to improve the efficiency of precise genome editing.