基于数据分析的NFASC与胃癌预后的关系及相关机制

目的:探讨NFASC在胃癌中的预后意义及相关机制。方法:从人类肿瘤相关基因表达汇编（Gene Expression Omibus，GEO）数据库中下载GSE62254胃癌数据集，分析NFASC表达与胃癌临床病理学参数的相关性及对预后的影响；利用Cox模型分析影响胃癌患者总生存期的因素并建立预后预测列线图模型；采用基因集富集分析(GSEA)方法预测NFASC参与的信号通路。结果: NFASC高表达的胃癌患者总生存时间（overall survival，OS）更短（P<0.05），NFASC表达与患者年龄、T分期及Lauren分型相关（P均<0.05）。NFASC高表达富集了TGF-β信号通路、mTOR信号通路、MAPK信号通路和Wnt信号通路等与肿瘤细胞增殖密切相关的通路（P<0.05，FDR<0.25）。结论: NFASC是胃癌的不良预后因素，其表达可能成为胃癌预后预测生物标志物。     

耳穴贴压联合中医饮食调护对糖尿病肾病患者的影响

目的:观察耳穴贴压联合中医饮食调护对糖尿病肾病患者的影响。方法:将糖尿病肾病患者60例按随机数字表法分成2组,对照组30例患者采用耳穴贴压治疗,观察组30例患者采用耳穴贴压联合中医饮食调护治疗。对比2组患者治疗前后肾功能指标、血清糖化血红蛋白、尿微量白蛋白、24h尿蛋白定量变化和肾小管损伤情况。结果:2组治疗后,血尿素氮(BUN)、内生肌酐清除率(CCr)、24 h尿白蛋白排泄率(UAE)和血肌酐(SCr)水平均明显优于治疗前,差异有统计学意义(P<0.05);治疗后,观察组肾功能指标BUN、CCr、UAE低于对照组,SCr则有所提高,差异有统计学意义(P<0.05)。2组患者治疗后,尿蛋白定量、尿微量白蛋白和血清糖化血红蛋白水平均明显优于治疗前,差异有统计学意义(P<0.05);观察组治疗后尿蛋白、尿微量白蛋白、血清糖化血红蛋白指标低于对照组,差异有统计学意义(P<0.05)。2组患者治疗后,β2-微球蛋白(β2-MG)和N-乙酰-β-D-氨基葡萄糖苷酶(NAG)水平均明显优于治疗前,差异有统计学意义(P<0.05);观察组治疗后肾小管损伤指标β2-MG、NAG低于对照组,差异有统计学意义(P<0.05)。结论:耳穴贴压联合中医饮食调护在糖尿病肾病患者中疗效明确,可改善肾功能指标,减轻肾小管损伤,改善临床症状。     

腰痛散循经火疗治疗寒湿腰痛临床研究

目的:观察腰痛散循经火疗治疗寒湿腰痛的临床疗效。方法:选取寒湿腰痛患者60例,按随机数字表法分为治疗组和对照组各30例。对照组采用腰痛散湿热敷,治疗组在对照组湿热敷的基础上运用腰痛散循经火疗。采用疼痛数字评分法(NRS)和日本骨科协会评估治疗分数(JOA)分别对2组患者进行客观评价,比较2组临床疗效。结果:治疗组总有效率为96.66%,显著高于对照组73.33%(P<0.05)。治疗前,2组NRS评分、JOA评分比较,差异均无统计学意义(P>0.05)。治疗后,2组NRS评分较治疗前降低,JOA评分较治疗前升高(P<0.05);且治疗组NRS评分低于对照组,JOA评分高于对照组(P<0.05)。结论:腰痛散循经火疗治疗寒湿腰痛效果显著,症状改善明显,安全有效,进一步提高了患者的生活质量。     

红景天苷通过TLR4调控DC提高T细胞对肺癌3LL细胞的杀伤力

目的：探讨红景天苷（salidroside，SAL）对树突状细胞（dendritic cell，DC）表型及细胞毒性T细胞（cytotoxic T lympho‐cyte，CTL）抗肿瘤能力的影响。方法：选用Lewis肺癌细胞株3LL、野生型C57BL/6和TLR4-/-C57BL/6小鼠，获取小鼠骨髓来源的DC前体细胞，经过培养分化成未成熟DC，收获第6天的DC，经磁珠分选后获得纯度较高的CD11c+DC。将细胞分成PBS组、SAL组和脂多糖（lipopolysaccharide，LPS）组，培养48 h后用流式细胞术检测SAL体外对DC表面分子、吞噬功能、TLR4通路和对T细胞杀伤能力的影响。结果：与 PBS 组比较，SAL组DC的表面分子CD80、CD86、MHC Ⅱ表达水平显著升高（均 P<0.05）、吞噬功能显著下降（P<0.05）、TLR4 表达水平显著升高（P<0.01）；与野生型组比较，TLR4-/-组DC经SAL或LPS处理后，其表面分子CD80、CD86、MHC Ⅱ的表达水平显著降低（均P<0.05）；与PBS组比较，SAL组刺激活化的CTL对肺癌3LL细胞的杀伤效应显著升高（P<0.05）。结论：SAL可以通过调控TLR4诱导DC成熟，从而提高T细胞的杀伤能力     

Evodiamine-inspired dual inhibitors of histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) with potent antitumor activity

A great challenge in multi-targeting drug discovery is to identify drug-like lead compounds with therapeutic advantages over single target inhibitors and drug combinations. Inspired by our previous efforts in designing antitumor evodiamine derivatives, herein selective histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) dual inhibitors were successfully identified, which showed potent in vitro and in vivo antitumor potency. Particularly, compound 30a was orally active and possessed excellent in vivo antitumor activity in the HCT116 xenograft model (TGI = 75.2%, 150 mg/kg, p.o.) without significant toxicity, which was more potent than HDAC inhibitor vorinostat, TOP inhibitor evodiamine and their combination. Taken together, this study highlights the therapeutic advantages of evodiamine-based HDAC1/TOP2 dual inhibitors and provides valuable leads for the development of novel multi-targeting antitumor agents.     

半归-菟丝子干预肾虚血瘀型多囊卵巢综合征网络药理学作用机制

目的:运用网络药理学方法和技术,研究"当归-菟丝子"药对治疗多囊卵巢综合征(PCOS)的主要活性成分、靶点、通路等药理学作用机制。方法:通过数据挖掘获得PCOS肾虚血瘀型核心药对当归-菟丝子;检索中药系统药理学分析平台(TCMSP)筛选出当归和菟丝子的活性成分和潜在靶点;查询NCBI数据库获得PCOS疾病靶点,找到药物和疾病的共靶点;通过David数据库和Omicshare数据库对共靶点进行基因功能GO富集分析和KEGG富集分析;采用Cytoscape软件构建成分-靶标-通路网络。结果:从"当归-菟丝子"药对中筛选得到42个候选活性分子,作用于719个靶点,其中与PCOS重合的22个疾病靶点主要涉及炎性反应、细胞因子、雌激素、胰岛素抵抗等生物学过程中的多条信号通路。结论:当归-菟丝子药对治疗PCOS是通过补肾活血化瘀达到抗炎、抗肿瘤、调节血脂、促进微循环及改善胰岛素抵抗,通过多成分、多靶点、多途径之间的协同作用来恢复机体的平衡,与现代治疗PCOS的作用机制相符合。     

中医药治疗系统性红斑狼疮证型及用药规律演变研究

目的:基于文献整理探讨中医药治疗系统性红斑狼疮(Systemic lupus erythematosus,SLE)的证候分类及用药规律演变。方法:检索中国知网(CNKI)、维普中文科技期刊数据库、中国学术期刊数据库中中医药治疗SLE的相关文献,时间限定为从数据库建立至2018年7月。对证型及药物进行分类并统计分析。结果:纳入文献725篇,总结归纳高频证型11个,出现频次最高的五个证型分别为热毒炽盛证、脾肾两(阳)虚证、阴虚内热(火旺)证、肝肾两(阴)虚证、气阴两虚证,累计频率62.11%。1965-2018年间,阴虚内热(火旺)证呈明显增长趋势;热毒炽盛证、脾肾两(阳)虚证及气阴两虚证在1965-2010年间呈增长趋势,在2011-2018年间呈下降趋势;肝郁气滞(脾虚)证在1965-2018年间呈下降趋势;其余证型均呈动态波动。涉及组方1522个,药物309味,使用15910次,总使用频率最高的5味药分别为生地黄、牡丹皮、茯苓、黄芪、甘草,总累计频率16.42%。使用频率最高药类为清热药和补虚药;生地黄、牡丹皮等清热药的使用频率趋势与热毒炽盛证保持一致,不同年份高频用药大致相似,用药频率存在较小差异。结论:SLE在内以阴阳亏虚为主,在外与热毒侵袭相关,属于本虚标实,其发展与生态环境、社会环境、药物使用等紧密相关,治当以清热凉血、活血祛瘀、益气养阴,并结合个人体质及环境变化辨证治疗。     

完全肿瘤细胞减灭术加腹腔热灌注化疗治疗胃癌腹膜转移的病例筛选策略

目的:构建肿瘤细胞减灭程度(completeness of cytoreduction,CC)预测模型,为肿瘤细胞减灭术(cytoreductive surgery,CRS)加腹腔热灌注化疗(hyperthermic intraperitoneal chemotherapy,HIPEC)治疗胃癌腹膜转移(gastric cancer with peritoneal metastasis,GCPM)提供病例筛选方法。方法:比较完全CRS(complete CRS,CCRS)组和不完全CRS(incomplete CRS,ICRS)组患者基本临床病理特征和治疗参数,通过逻辑回归模型筛选CC独立预测因子,精准预测CCRS可能性。结果:125例患者纳入本研究,其中CC0组52例(41.6%),中位总生存期为30.0(95%CI:16.8~43.3)个月;CC1-3组73例,中位总生存期7.3(95%CI:5.7~8.8)个月,差异有统计学意义(P<0.001),而CC1、CC2和CC3组间中位总生存期差异无统计学意义(P>0.05)。因此,CC0定义为CCRS组,CC1-3定义为ICRS组,构建并优化了以腹膜转移时相(OR=14,95%CI:2.0~97.9,P=0.008)、术前肿瘤标志物(OR=6.5,95%CI:2.1~37.8,P=0.037)和腹膜癌指数(OR=1.5,95%CI:1.3~1.8,P<0.001)预测ICRS的多因素回归模型和预测列线图,内部验证显示,ROC曲线下面积为0.985,列线图显示预测准确度、一致性良好。根据列线图结果将患者分为4个亚组,设定CCRS预测概率≥50%,同时性且术前肿瘤标志物正常组、同时性且术前肿瘤标志物异常组、异时性且术前肿瘤标志物正常组、异时性且术前肿瘤标志物异常组腹膜癌指数界值点分别为:≤16、≤12、≤10和≤5。结论:CCRS+HIPEC可延长部分经选择的GCPM患者生存期,以腹膜癌指数为核心,联合腹膜转移时相和术前肿瘤标志物的病例筛选策略,可有效选择高概率实现CCRS的患者接受CCRS+HIPEC治疗。     

Use of Machine Learning and Artificial Intelligence to predict SARS-CoV-2 infection from Full Blood Counts in a population

Since December 2019 the novel coronavirus SARS-CoV-2 has been identified as the cause of the pandemic COVID-19. Early symptoms overlap with other common conditions such as common cold and Influenza, making early screening and diagnosis are crucial goals for health practitioners. The aim of the study was to use machine learning (ML), an artificial neural network (ANN) and a simple statistical test to identify SARS-CoV-2 positive patients from full blood counts without knowledge of symptoms or history of the individuals. The dataset included in the analysis and training contains anonymized full blood counts results from patients seen at the Hospital Israelita Albert Einstein, at São Paulo, Brazil, and who had samples collected to perform the SARS-CoV-2 rt-PCR test during a visit to the hospital. Patient data was anonymised by the hospital, clinical data was standardized to have a mean of zero and a unit standard deviation. This data was made public with the aim to allow researchers to develop ways to enable the hospital to rapidly predict and potentially identify SARS-CoV-2 positive patients.We find that with full blood counts random forest, shallow learning and a flexible ANN model predict SARS-CoV-2 patients with high accuracy between populations on regular wards (AUC = 94–95%) and those not admitted to hospital or in the community (AUC = 80–86%). Here, AUC is the Area Under the receiver operating characteristics Curve and a measure for model performance. Moreover, a simple linear combination of 4 blood counts can be used to have an AUC of 85% for patients within the community. The normalised data of different blood parameters from SARS-CoV-2 positive patients exhibit a decrease in platelets, leukocytes, eosinophils, basophils and lymphocytes, and an increase in monocytes.SARS-CoV-2 positive patients exhibit a characteristic immune response profile pattern and changes in different parameters measured in the full blood count that are detected from simple and rapid blood tests. While symptoms at an early stage of infection are known to overlap with other common conditions, parameters of the full blood counts can be analysed to distinguish the viral type at an earlier stage than current rt-PCR tests for SARS-CoV-2 allow at present. This new methodology has potential to greatly improve initial screening for patients where PCR based diagnostic tools are limited.