人滋养细胞表面抗原（Trop-2）在病变子宫内膜中表达的研究

摘要 目的：探讨人滋养细胞表面抗原（trophoblast cell-surface antigens2,Trop-2）在病变子宫内膜中的表达及其临床相关性。方法：采用免疫组化法检测100例正常子宫内膜或病变子宫内膜组织中Trop-2蛋白的表达,其中单纯增生子宫内膜患者26例,复杂或不典型增生子宫内膜患者34例,子宫内膜腺癌患者20例,对照组为20例增生期子宫内膜患者。结果：免疫组织化学法研究结果显示,Trop-2蛋白在正常增生子宫内膜和单纯性增生子宫内膜中几乎不表达,在复杂或不典型增生子宫内膜组织中以及子宫内膜腺癌呈阳性表达。主要分布在细胞膜上,阳性率分别为35.29 %和65.00 %,经过对比子宫内膜癌组的阳性表达率显著高于复杂型或伴不典型增生子宫内膜组的阳性表达率（P<0.05）,且复杂型或伴不典型增生子宫内膜组的阳性表达率显著高于单纯性增生子宫内膜组（P<0.05）,其表达水平随内膜病变程度的加重而升高,呈正相关关系（P＜0.05）。结论：Trop-2蛋白在子宫内膜病变中的表达与其严重程度一致,可反映子宫内膜病变的发生发展,或可作为判断其严重程度的指标。     

乌司他丁联合连续性肾脏替代治疗对严重脓毒症患者炎症反应和血流动力学的影响

目的:探讨乌司他丁联合连续性肾脏替代(CRRT)治疗对严重脓毒症患者炎症反应和血流动力学的影响。方法:选取2015年5月～2019年4月期间我院收治的严重脓毒症患者119例,将所有患者根据随机数字表法分为对照组(n=59)和研究组(n=60),对照组给予CRRT治疗,研究组在对照组基础上联合乌司他丁治疗,比较两组患者临床疗效、炎症反应指标、血流动力学参数,记录两组患者住院时间及28d内病死率。结果:研究组治疗7 d后的临床总有效率高于对照组(P0.05)。两组治疗7 d后血清白介素-6(IL-6)、降钙素原(PCT)、肿瘤坏死因子-α(TNF-α)水平均下降,且研究组低于对照组(P0.05)。两组患者治疗7 d后心率、平均动脉压(MAP)、血乳酸下降,氧合指数升高(P0.05),研究组治疗7 d后氧合指数高于对照组,血乳酸则低于对照组(P0.05)。研究组住院时间短于对照组(P0.05),两组28d内病死率比较无统计学差异(P0.05)。结论:乌司他丁联合CRRT治疗严重脓毒症患者的疗效确切,可有效抑制机体炎症反应,改善血流动力学,减少住院时间,具有一定的临床应用价值。     

气候变化和经济发展对肾综合征出血热发生的影响

肾综合征出血热(hemorrhagic fever with renal syndrome, HFRS)是一种啮齿动物传播的自然疫源性疾病, 危害严重, 已成为全球重要的公共卫生问题。本研究采用数理统计模型及小波分析方法, 对陕西省西安市鄠邑区1984-2016年HFRS的发生与鼠类、气候和经济因素的关系进行分析, 探讨气候和经济因素对HFRS发生的影响。小波分析结果表明, 该地区的HFRS暴发史可能分为两个时期, 推测每个时期具有不同的主要宿主, 在2002年褐家鼠(Rattus norvegicus)可能取代黑线姬鼠(Apodemus agrarius)成为HFRS疫源地的主要宿主。广义可加模型模拟结果表明, HFRS的发生与1984-2001年黑线姬鼠密度间存在极显著非线性效应(F_2.06,9.02 = 102.415, P < 0.01), 两者间显现为正相关; 与2002-2016年的褐家鼠密度间呈正相关(F_1.67,9.02 = 73.929, P < 0.01); HFRS主要宿主的这种变化可能与当地气候变化和经济发展有关: HFRS的发生与年平均温度存在极显著的非线性效应(F_2.93,9.02 = 12.164, P < 0.01), 两者间呈负相关; 同样, HFRS的发生与上一年的国内生产总值(GDP)也存在显著非线性效应(F_1.70,9.02 = 2.917, P < 0.05), 两者间也呈负相关。结构方程模型通过直接和间接的影响途径证明了这种转移机制, 发现温度对HFRS发生有显著的直接负向影响以及通过褐家鼠的间接正向影响; GDP对HFRS发生有直接的负向影响。本研究表明HFRS的发生与气候变化和经济发展相关, 两者均能影响HFRS的暴发, 该结论有助于今后更好地对HFRS疾病进行预防和控制。     

Penalized survival models for the analysis of alternating recurrent event data

Recurrent event data are widely encountered in clinical and observational studies. Most methods for recurrent events treat the outcome as a point process and, as such, neglect any associated event duration. This generally leads to a less informative and potentially biased analysis. We propose a joint model for the recurrent event rate (of incidence) and duration. The two processes are linked through a bivariate normal frailty. For example, when the event is hospitalization, we can treat the time to admission and length-of-stay as two alternating recurrent events. In our method, the regression parameters are estimated through a penalized partial likelihood, and the variance-covariance matrix of the frailty is estimated through a recursive estimating formula. Moreover, we develop a likelihood ratio test to assess the dependence between the incidence and duration processes. Simulation results demonstrate that our method provides accurate parameter estimation, with a relatively fast computation time. We illustrate the methods through an analysis of hospitalizations among end-stage renal disease patients.     

Study of FABP's interactome and detecting new molecular targets in clear cell renal cell carcinoma

Fatty acids (FAs) play a crucial role in the development of clear cell renal cell carcinoma (ccRCC), FAs function requires the participation of fatty-acid-binding protein (FABP). Current studies have shown that different members of the FABP's family play different roles in the tumorigenesis of ccRCC. Therefore, the systematic analysis of FABPs will be of great significance. However, the diverse expression patterns and prognostic values of nine FABPs have yet to be elucidated. In this study, through multiple analysis and verification of multiple databases, such as ONCOMINE, The Human Protein Atlas, UALCAN, Gene Expression Profiling Interactive Analysis, and cBioPortal, we found that the expression of FABP1 was significantly downregulated and the expression of FABP5/6/7 was significantly upregulated in ccRCC compared with renal tissues, and the patients with high messenger RNA (mRNA) levels of the FABP5/6/7 or low mRNA levels of FABP1 were predicted to have a lower overall survival or disease-free survival. Further analysis by the protein–protein interaction (PPI), Gene Ontology pathway, and Kyoto Encyclopedia of Genes and Genomes pathway showed that FABPs were mainly involved in the peroxisome proliferator-activated receptor (PPAR) pathway. In coexpression analysis, we found that FABP1/5/6/7 was coexpressed with transforming growth factor-β1 (TGF-β1), PPARA, and LPL. This study implied that FABP1/5/6/7 could act as an important tumor biomarker of ccRCC; the role of FABPs may be related to PPAR or TGF-β pathway.     

Identification of methylation-driven genes related to prognosis in clear-cell renal cell carcinoma

With the participation of the existing treatment methods, the prognosis of advanced clear-cell renal cell carcinoma (ccRCC) is poor. More evidence indicates the presence of methylation in ccRCC cancer cells, but there is a lack of studies on methylation-driven genes in ccRCC. We analyzed the open data of ccRCC in The Cancer Genome Atlas database to obtain ccRCC-related methylation-driven genes, and then carried out pathway enrichment, survival, and joint survival analyses. More important, we deeply explored the correlation between differential methylation sites and the expression of these driving genes. Finally, we screened 29 methylation-driven genes via MethylMix, of which six were significantly associated with the survival of ccRCC patients. This study demonstrated that the effect of hypermethylation or hypomethylation on prognosis is different, and the level of methylation of key methylation sites is associated with gene expression. We identified methylation-driven genes independently predicting prognosis in ccRCC, which offers theoretical support in bioinformatics for the study of methylation in ccRCC and a new perspective for the epigenetic study of ccRCC.     

Identification of novel prognostic alternative splicing signature in papillary renal cell carcinoma

Papillary renal cell carcinoma (pRCC) is a heterogeneous disease containing multifocal or solitary tumors with an aggressive phenotype. Increasing evidence has indicated the involvement of aberrant splicing variants in renal cell cancer, while systematic profiling of aberrant alternative splicing (AS) in pRCC was lacking and largely unknown. In the current study, comprehensive profiling of AS events were performed based on the integration of pRCC cohort from the Cancer Genome Atlas database and SpliceSeq software. With rigorous screening and univariate Cox analysis, a total of 2077 prognoses AS events from 1642 parent genes were identified. Then, stepwise least absolute shrinkage and selection operator method-penalized Cox regression analyses with 10-fold cross-validation followed by multivariate Cox regression were used to construct the prognostic AS signatures within each AS type. And a final 21 AS event-based signature was proposed which showed potent prognostic capability in stratifying patients into low- and high-risk subgroups (P < .0001). Furthermore, time-dependent receiver operating characteristics curves confirmed that the final AS signature was effective and robust in predicting overall survival for pRCC patients with the area under the curve above 0.9 from 1 to 5 years. In addition, splicing correlation network was built to uncover the potential regulatory pattern among prognostic splicing factors and candidate AS events. Besides, gene set enrichment analysis revealed the involvement of these candidates AS events in tumor-related pathways including extracellular matrix organization, oxidative phosphorylation, and P53 signaling pathways. Taken together, our results could contribute to elucidating the underlying mechanism of AS in the oncogenesis process and broaden the novel field of prognostic and clinical application of molecule-targeted approaches in pRCC.     

果蝇干细胞研究进展

本文主要介绍了果蝇五种干细胞,包括生殖干细胞、神经干细胞、造血干细胞、小肠干细胞、肾干细胞及其微环境（niche）的组成成份;简述了五种干细胞系统对应的分子标记;最后重点介绍了调控每种干细胞系统的信号通路。     

斑潜蝇及天敌复合生态系统的主成份分析方法

本文以蚕豆田间斑潜蝇及天敌复合生态系统为例,首先确定了复合生态系统中的昆虫种群,然后运用主成份分析方法对复合生态系统起主要作用的昆虫种群进行了分析,并进一步建立评价函数对复合生态系统各时期进行评分并排序,比较复合生态系统各时期复合体的大小,其结果可直接用于指导实践.