子宫浆液性癌的分子学特征及靶向治疗研究进展

子宫浆液性癌（uterine serous carcinoma,USC）是一种特殊类型的子宫内膜癌。有别于常见的子宫内膜样腺癌,USC较为少见,且恶性程度高,侵袭转移风险高,临床上预后较差。随着子宫内膜癌分子学研究的不断深入,分子学特征被应用于子宫内膜癌的病理分型诊断、治疗和预后评价中。研究发现USC中存在多种基因的突变,这些相关基因的突变对该病的诊断和预后具有重要的指导意义。同时,特异性的分子学改变为USC的靶向治疗提供了潜在的治疗靶点。目前,多种靶向治疗手段包括人表皮生长因子受体2（human epidermal growth factor receptor 2,HER2）抑制剂、免疫检查点抑制剂、抗血管生成治疗、磷脂酰肌醇3激酶（phosphoinositide 3-kinases,PI3K）通路抑制剂和多腺苷二磷酸核糖聚合酶[poly(ADP-ribose) polymerase,PARP]抑制剂等被应用于USC的临床治疗研究中,针对性的靶向治疗有望成为USC治疗的新突破。     

A prognostic signature based on immune-related genes for cervical squamous cell carcinoma and endocervical adenocarcinoma

Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) is the fourth commonest female malignancy worldwide. CESC progresses in immune-microenvironment mainly composed of infiltrating immune and stromal cells. Here, we performed an integrated analysis incorporating the expression profiles from the Cancer Genome Atlas (TCGA) database and scores of immune and stromal cells calculated by Estimation of Stromal and Immune cells in Malignant Tumours using Expression data (ESTIMATE) algorithm. A two-gene signature (CD1C and CD6 genes) was established to predict the prognosis of CESC. Based on this signature, patients were divided into the high- and low-risk groups, and this signature showed good prognostic performance according to the results of Kaplan-Meier analysis and receiver operating characteristic (ROC) analysis in train set and two validation sets. A nomogram was built for evaluating the clinical applicability of this signature. In addition, based on Tumor Immune Estimation Resource (TIMER) database, 2 hub genes showed negative correlations with tumor purity and positive correlations with infiltrating levels of immune filtrating cells. What’s more, we propose new treatment strategies for the two prognostic subtypes. Low- risk patients were found presenting with a higher level of immune checkpoint molecules and showing higher immunogenicity in immunophenoscore (IPS) analysis, which indicated a better response for immunotherapy. Meanwhile, estimated by Genomics of Drug Sensitivity in Cancer (GDSC) database, the high-risk patients showed sensitive responses to five chemotherapy drugs. Finally, 10 candidate small-molecule drugs for CESC were defined. In summary, the CD1C-CD6 signature can accurately predict the prognosis of CESC.     

Identification of key genes and pathways in discoid lupus skin via bioinformatics analysis

Discoid lupus erythematosus (DLE) is the most common skin manifestation of lupus; however, the molecular mechanisms underlying DLE remain unknown. Therefore, we aimed to identify key differentially expressed genes (DEGs) in discoid lupus skin and investigate their potential pathways.To identify candidate genes involved in the occurrence and development of the disease, we downloaded the microarray datasets {"type":"entrez-geo","attrs":{"text":"GSE52471","term_id":"52471"}}GSE52471 and {"type":"entrez-geo","attrs":{"text":"GSE72535","term_id":"72535"}}GSE72535 from the Gene Expression Database (GEO). DEGs between discoid lupus skin and normal controls were selected using the GEO2R tool and Venn diagram software (http://bioinformatics.psb.ugent.be/webtools/Venn/). The Database for Annotation, Visualization, and Integrated Discovery (DAVID), Enrichr, and Cytoscape ClueGo were used to analyze the Kyoto Encyclopedia of Gene and Genome pathways and gene ontology. Protein-protein interactions (PPIs) of these DEGs were further assessed using the Search Tool for the Retrieval Interacting Genes version 10.0.Seventy three DEGs were co-expressed in both datasets. DEGs were predominantly upregulated in receptor signaling pathways of the immune response. In the PPI network, 69 upregulated genes were selected. Furthermore, 4 genes (CXCL10, ISG15, IFIH1, and IRF7) were found to be significantly upregulated in the RIG-I-like receptor signaling pathway, from analysis of Enrichr and Cytoscape ClueGo.The results of this study may provide new insights into the potential molecular mechanisms of DLE. However, further experimentation is required to confirm these findings.     

子痫前期高危孕妇阿司匹林抵抗与基因多态性相关性

子痫前期是妊娠期特有的高血压疾病，近年尤其是早发型子痫前期，是孕产妇和新生儿发病和死亡的重要原因。低剂量的阿司匹林在国外已明确用于子痫前期的预防，可以减少子痫前期的发展，并降低早产和胎儿生长受限的发生率。但部分患者不能达到预期效果，存在阿司匹林抵抗。在阿司匹林预防血栓相关研究中同样存在阿司匹林抵抗现象。目前基因多态性与阿司匹林抵抗的相关性已成为研究热点。研究较多的有ABC转运蛋白家族基因、环氧合酶（COX）基因（COX-1和COX-2）、TXA2R基因、ADP受体基因、GP受体等基因多态性及其相互作用。由于其在孕妇中鲜有研究而在心脑血管疾病中研究较多，现重点从基因多态性角度阐述在心脑血管疾病中阿司匹林抵抗的可能机制，以指导阿司匹林在孕妇这类特殊人群的用药，改善妊娠结局。     

葡萄糖激酶W257R突变致青少年发病的成人型糖尿病一家系分析

青少年发病的成人型糖尿病（MODY）是一类以常染色体显性模式遗传的单基因疾病，临床表现以无症状、轻度空腹血糖升高为特征，很少出现糖尿病并发症。本文报道一例中国人群中葡萄糖激酶（GCK）基因新发W257R突变所致的MODY。在先证者及父亲、弟弟中均发现GCK基因（Chr744187343）第7号外显子的杂合突变c.769T>C（p.W257R）。该家系中W257R突变在中国人群中为首发。     

Interstitial lung diseases in children

Interstitial lung disease (ILD) in children (chILD) is a heterogeneous group of rare respiratory disorders that are mostly chronic and associated with high morbidity and mortality. The pathogenesis of the various chILD is complex and the diseases share common features of inflammatory and fibrotic changes of the lung parenchyma that impair gas exchanges. The etiologies of chILD are numerous. In this review, we chose to classify them as ILD related to exposure/environment insults, ILD related to systemic and immunological diseases, ILD related to primary lung parenchyma dysfunctions and ILD specific to infancy. A growing part of the etiologic spectrum of chILD is being attributed to molecular defects. Currently, the main genetic mutations associated with chILD are identified in the surfactant genes SFTPA1, SFTPA2, SFTPB, SFTPC, ABCA3 and NKX2-1. Other genetic contributors include mutations in MARS, CSF2RA and CSF2RB in pulmonary alveolar proteinosis, and mutations in TMEM173 and COPA in specific auto-inflammatory forms of chILD. However, only few genotype-phenotype correlations could be identified so far. Herein, information is provided about the clinical presentation and the diagnosis approach of chILD. Despite improvements in patient management, the therapeutic strategies are still relying mostly on corticosteroids although specific therapies are emerging. Larger longitudinal cohorts of patients are being gathered through ongoing international collaborations to improve disease knowledge and targeted therapies. Thus, it is expected that children with ILD will be able to reach the adulthood transition in a better condition.     

斑驳病致病基因的研究进展

斑驳病是一种较少见的由黑素细胞发育不良引起的常染色体显性遗传病,典型临床特征是先天性额部中央呈三角形或菱形的白斑和白发.该病具有遗传异质性,大多数斑驳病由kit基因突变引起.遗传分析揭示,kit基因突变点与临床表型关系密切,少数报告表明,可能存在其他因素引起基因型与表型不一致,有学者对该病的常染色体显性遗传特点提出质疑.kit基因编码蛋白属Ⅲ型酪氨酸激酶受体,kit基因突变导致受体酪氨酸激酶功能下降或失活,信号传导功能受损,成黑素细胞在胚胎发育期的增殖和迁移发生障碍,从而导致斑驳病的发生.     

强直性脊柱炎异位骨化机制研究进展

强直性脊柱炎是一种发病机制不明的慢性炎性脊柱关节病,主要侵犯骶髂关节、脊柱关节等,严重者可发生脊柱、关节的畸形和强直。临床表现为炎性腰背痛,夜间及休息后加重,活动后减轻。该病发病率男性高于女性,且男性主要表现为中轴关节改变,而女性大多首发于外周关节。目前生物制剂肿瘤坏死因子抑制剂通过控制炎症,从而改善病情发展,被认为是最前沿的药物,但其在阻断新骨形成方面尚未经循证医学证实有效。本文着眼于新骨形成角度,从基因及细胞因子层面探讨强直性脊柱炎的病因。目前相关研究发现LRP5、ANTXR2、PTGER4、ANKH等基因的异常表达激活骨形成信号通路,在多种细胞因子及相关蛋白(如Noggin蛋白、DKK、转化生长因子-β、骨形态发生蛋白、碳酸酐酶1等)直接或间接作用下将骨形成信号传至靶细胞表面,进而传入细胞核,改变靶细胞正常生理代谢过程,导致过度骨形成,造成异位骨化。近年的临床影像学病例分析也提示了骨赘形成的分布特点,进而推断机械应力是促进其形成的外部因素。本文对强直性脊柱炎异位骨化方面进行了文献综述,以期待能进一步加深对本病的认识,为临床治疗研究提供新的思路。