基于生物信息学筛选早发性乳腺癌差异表达基因

目的筛选并分析与早发性乳腺癌发生、发展相关的靶基因。 方法(1)在美国国立生物技术信息中心的公共基因芯片数据库(GEO)中检索早发性乳腺癌样本及非早发性乳腺癌样本相关基因芯片数据。对上述数据使用GEO2R、R4.1.2及Venn软件筛选出相关差异表达基因(DEGs)，并运用在线分析工具(Web Gestalt)对DEGs，进行相关功能和信号通路富集分析。(2)同时，通过String在线数据库构建DEGs编码的蛋白质-蛋白质相互作用(PPI)网络，并利用Cytohubba插件对该网络中的基因进行评分，筛选出枢纽基因。将枢纽基因导入Kaplan-Meier生存分析工具(Kaplan-Meier Plotter)，评估枢纽基因在早发性乳腺癌的预后价值。(3)将肿瘤基因组图谱(TCGA)数据库中的肿瘤组织以年龄为标准进行分组，分析枢纽基因在各年龄组中的表达，并与正常组织中的表达进行比较，对得到的枢纽基因进行验证。DEGs表达量的多组间比较使用Kruskal-Wallis H检验，使用Bonferroni法进行两两比较。 结果(1)筛选出编号为GSE89116、GSE109169、GSE36295的基因芯片数据集，共得到80个差异表达基因，其中上调差异表达基因17个，下调差异表达基因63个。富集分析显示：DEGs主要富集在脂质代谢和氧化还原过程以及PPAR信号通路、AMPK信号通路上。(2)在PPI中发现主要的关键基因为PPARG、ADIPOQ、LIPE、PCK1、PDK4、ACACB、PLIN1、CAV1、CD36、ANGPTL4。ACACB、ADIPOQ、CAV1、LIPE、PLIN1、PPARG基因的低表达与乳腺癌患者的不良OS相关(HR＝0.69、0.84、0.76、0.88、0.78、0.82；95%CI：0.59~0.80、0.76~0.93、0.67~0.83、0.79~0.97、0.70~0.86、0.73~0.90；P均<0.050)。(3)ACACB、ADIPOQ、LIPE、PLIN1、CAV1及PPARG这6个与预后相关的基因在正常组织中的表达量均远高于各年龄组肿瘤组织中的表达量(χ²＝104.03、179.57、161.85、189.87、118.56、103.62，P均<0.001)，早发性乳腺癌组(21~40岁)的LIPE、PLIN1表达量低于41~60岁、61~80岁年龄组，差异具有统计学意义(LIPE: Z＝21.07、23.12, P均<0.050; PLIN1：Z＝16.89、18.76, P均<0.050)。 结论早发性乳腺癌与非早发性乳腺癌存在差异基因表达谱，LIPE、PLIN1可能是早发性乳腺癌发生、发展的关键基因。     

狼疮肾炎合并抗磷脂抗体综合征的中西医结合诊疗

抗磷脂抗体综合征(APS)是系统性红斑狼疮(SLE)常见继发病症。以循环中出现抗磷脂抗体、血栓形成和病态妊娠为特征性表现。合并APS的狼疮肾炎(LN)患者易出现更多并发症，预后较差，对治疗的敏感性降低。抗凝和(或)抗血小板是治疗LN合并APS的关键，血浆置换则对重症APS患者有一定疗效。近年来，新型药物与治疗方法如利伐沙班、美罗华及干细胞移植展现出了巨大的治疗潜力。中西医结合治疗是另一种极有希望的治疗方法，多位中医大家均认为活血化瘀法可有效治疗LN合并APS患者。现代临床与药理研究也发现了中药治疗LN合并APS的价值。     

Two novel genetic variants in the STK38L and RAB27A genes are associated with glioma susceptibility

Glioma is the most common malignant primary brain tumors with poor prognosis. Genome wide association studies (GWAS) of glioma in populations with Western European ancestry were completed in the US and UK. However, our previous results strongly suggest the genetic heterogeneity could be important in glioma risk. To systematically investigate glioma risk–associated variants in Chinese population, we performed a multistage GWAS of glioma in the Han Chinese population, with a total of 3,097 glioma cases and 4,362 controls. In addition to confirming two associations reported in other ancestry groups, this study identified one new risk-associated locus for glioma on chromosome 12p11.23 (rs10842893, p_meta = 2.33x10-12, STK38L) as well as a promising association at 15q15-21.1 (rs4774756, p_meta = 6.12x10-8, RAB27A) in 3,097 glioma cases and 4,362 controls. Our findings demonstrate two novel association between the glioma risk region marked by variant rs10842893 and rs4774756) and glioma risk. These findings may advance the understanding of genetic susceptibility to glioma.     

多学科管理下鸟氨酸氨甲酰基转移酶缺乏症妇女连续三次妊娠分娩健康儿一例

本文报告1例鸟氨酸氨甲酰基转移酶缺乏症患者3次妊娠,最终在多学科管理下分娩一健康新生儿的诊疗经过。2013年患者首次妊娠,孕28周出现急性高氨血症收入上海交通大学医学院附属新华医院,诊断为鸟氨酸氨甲酰基转移酶缺乏症。给予低蛋白饮食及降血氨治疗,并在多学科管理下于孕32周剖宫产一男婴,但该男婴生后第3天死亡。基因分析提示患者及其新生儿鸟氨酸氨甲酰基转移酶基因均存在c.583G>A(G195R)突变。2015年患者再次自然妊娠,但产前诊断提示胎儿为男性,且鸟氨酸氨甲酰基转移酶基因存在同一位点纯合突变,于孕21周引产终止妊娠。2017年借助体外受精-胚胎移植及植入前基因诊断技术第3次妊娠,并在多学科管理下最终顺利分娩一名健康男婴。     

Dynamic biomechanical effect of lower body positive pressure treadmill training for hemiplegic gait rehabilitation after stroke: A case report

BACKGROUNDLower body positive pressure (LBPP) treadmill has potential applications for improving the gait of patients after stroke, but the related mechanism remains unclear.CASE SUMMARYA 62-year-old male patient suffered from ischemic stroke with hemiplegic gait. He was referred to our hospital because of a complaint of left limb weakness for 2 years. The LBPP training was performed one session per day and six times per week for 2 wk. The dynamic plantar pressure analysis was taken every 2 d. Meanwhile, three-digital gait analysis and synchronous electromyography as well as clinical assessments were taken before and after LBPP intervention and at the 4-wk follow-up. During LBPP training, our patient not only improved his lower limb muscle strength and walking speed, but more importantly, the symmetry index of various biomechanical indicators improved. Moreover, the patient’s planter pressure transferring from the heel area to toe area among the LBPP training process and the symmetry of lower body biomechanical parameters improved.CONCLUSIONIn this study, we documented a dynamic improvement of gait performance in a stroke patient under LBPP training, which included lower limb muscle strength, walking speed, and symmetry of lower limb biomechanics. Our study provides some crucial clues about the potential dynamic mechanism for LBPP training on gait and balance improvement, which is related to rebuilding foot pressure distribution and remodeling symmetry of biomechanics of the lower limb.     

基于大自然时间轴的测量时序分类法

因果推断中，时序（或方向性）的概念尚未完全明确。本文从因果思维出发，以真实因和真实果的发生时间将大自然时间轴划分为3个时域和2个时点，从而锚定了因果推断只能实现于第3时域。测量时序可分为5种类型：跨第1和3时域纵向时序（实验性时序）、跨第2和3时域纵向时序、同时域纵向时序、同时域逆纵向时序和同时域横向时序（观察性时序）。这种分类法适用于首次或多次测量、及时和延后测量等所有测量策略。除了实验中真实因的测量（或干预措施）在其发生之前（第1时域）或观察和实验中真实因的测量在真实果发生之前（第2时域）的情形外，所有其他测量策略类似于历史重建或"考古"，测量时序的重要性次于测量的准确性。从研究设计应整合偏倚设计的观点来看，本文提出基于大自然时间轴的测量时序五分类法，概念清楚并将有助于判断研究过程中可能出现的偏倚，为正确进行因果推断研究奠定基础。     

Reconstruction of skull base bone defects using an in situ bone flap after endoscopic endonasal transplanum-transtuberculum approaches

European Archives of Oto-Rhino-Laryngology - The creation of bone flaps which can be later repositioned and fixed in situ for repairing the bone defects during the endoscopic endonasal approaches...     

复发胶质瘤的病理学特征及其预后分析

目的探讨复发胶质瘤的病理学特征及其与患者预后的关系。方法回顾性分析2002年8月到2016年12月中山大学肿瘤防治中心神经外科收治的54例复发胶质瘤患者的临床资料。所有患者均再次行肿瘤切除术治疗,术后行病理学检测,包括肿瘤的世界卫生组织(WHO)分级、Ki-67指数、O6-甲基鸟嘌呤-DNA-甲基转移酶(MGMT)表达状态、异柠檬酸脱氢酶1(IDH1)状态;同时根据组织坏死程度、是否存在肿瘤细胞及肿瘤细胞活性情况进行病理学分型。采用Kaplan-Meier法分析患者的总生存期(OS)。进一步采用单因素和多因素Cox回归分析法判断影响复发胶质瘤患者OS的临床因素。结果54例患者的病理学检测结果,(1)WHO分级:Ⅱ级6例(11.1%)、Ⅲ级14例(25.9%)、Ⅳ级30例(55.6%),另4例(7.4%)未见肿瘤细胞。与初次手术比较,32例患者(59.2%)的WHO分级无变化,7例(13.0%)降低,15例(27.8%)升高。(2)Ki-67指数:共32例两次均行相关检测,其中15例的Ki-67指数降低、14例升高,另3例无改变。(3)IDH1状态:共29例两次均行相关检测,其中9例为突变型,20例为野生型;两次检测均未发生变化。(4)MGMT表达状态:共8例两次均行相关检测,6例无变化,其中3例表达阳性、3例表达阴性;另2例结果改变,均为初次表达阳性,二次表达阴性。(5)病理学分型:4例为坏死型,20例为混合型,30例为活性型。54例患者的随访时间为(16.1±3.2)个月(1.3~160.3)个月。Kaplan-Meier法分析结果显示,54例患者的中位OS(范围)为14.4个月(9.2~19.5个月)。多因素Cox回归分析结果显示,复发肿瘤WHO分级高(HR=2.80,95%CI:1.42~5.53,P<0.01)和术后未行放疗(HR=4.05,95%CI:1.41~11.64,P=0.01)是影响复发胶质瘤患者OS的独立危险因素。结论初步提示复发胶质瘤再次手术后的组织病理学会发生变化;再次手术后WHO病理分级低和术后行放疗是复发胶质瘤患者预后较好的临床因素。     

Comprehensive analysis of tumor immune infiltration associated with endogenous competitive RNA networks in lung adenocarcinoma

Cancer immunotherapy has achieved unprecedented success in the treatment of cancer. However, different patients have different responses to immunotherapy. More and more studies have shown that tumor immune heterogeneity has an important influence on the prognosis of cancer. Therefore, understanding the clinical impact of tumor immune infiltration and the regulatory mechanism of RNA molecules is crucial for exploring the pathogenesis of lung adenocarcinoma (LUAD) and the development of immunotherapy protocols.The endogenous competitive RNA hypothesis provides new ideas for studying immune heterogeneity. Therefore, by using the method of immune genomics, this article explores the relationship between immune infiltration and prognosis of patients with lung adenocarcinoma, and found that B-cell immune infiltration highly affects the survival of patients. Through differential analysis, differential mRNAs, lncRNAs and miRNAs were extracted, and 318 differentially expressed mRNAs related to B cell immunity were screened by correlation analysis, and prognosis of patients with COX risk regression model was predicted and analyzed. Through multiple database searches, an immune-related ceRNA regulatory network was constructed, containing 3 key mRNAs, 4 miRNAs, and 50 lncRNAs. Three mRNAs and most miRNAs, lncRNAs, are significantly associated with LUAD prognosis. Bioinformatics analysis of the network showed that LINC00337 may up-regulate the expression of PBK and KIF23 through competitive binding of has-mir-373 and has-mir-519d. The competitive binding of has-mir-373 and has-mir-372 can up-regulate the expression of SLC7A11. The interaction between these RNAs may have an important regulatory role in the immune infiltration in lung adenocarcinoma, thereby affecting the patient's prognosis and immunotherapy efficacy.