LncRNA XIST acts as a MicroRNA-520 sponge to regulate the Cisplatin resistance in NSCLC cells by mediating BAX through CeRNA network

Background: In recent years, LncRNA acts as a member of competing endogenous RNA (ceRNA), playing an important role in drug resistance of lung cancer. The aim of this study was to identify potential biomarkers about cisplatin resistant lung cancer cells using a comprehensive ceRNA network.Methods: {"type":"entrez-geo","attrs":{"text":"GSE6410","term_id":"6410"}}GSE6410 (GPL-201) analyzed gene expression changes about cisplatin resistance in A549 NSCLC cells. {"type":"entrez-geo","attrs":{"text":"GSE43249","term_id":"43249"}}GSE43249 (GPL-14613) included noncoding RNA expression profiling derived from the cisplatin resistant A549 lung cells. GEO2R, an online analysis tool, analyzed the differentially expressed mRNAs and miRNAs (DEmRNAs and DEmiRNAs). To explore the functional enrichment implication of differentially expressed mRNAs, we used the GO (Gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis. Through miRDB, Targetscan, Starbase and miRWalk, we found targeted miRNAs. The Kaplan-Meier curve method was used to show clinical survival analysis of targeted RNAs (P<0.05). The Starbase database predicted potential lncRNAs mediated targeted miRNAs. Eventually, the novel ceRNA network of lncRNAs, miRNAs, mRNA was constructed by cytoscape3.7.2.Results: 118 differentially expressed mRNAs were the basis of the mediated ceRNA network. DAVID and Kaplan-Meier picked out BAX, an apoptosis regulator. Venn diagram demonstrated 8 miRNAs commonly regulating BAX. Starbase predicted lncRNA XIST mediated miRNAs. Finally, lncRNA XIST may be a useful biomarker regulating cisplatin resistance in lung cancer cells and further, we explored the BAX may effect tumor-infiltrating immune cells.Conclusions: LncRNA XIST competitively bound to miRNA 520 in the regulation of cisplatin resistance by BAX, participating apoptosis in the p53 signaling pathway.     

Cost–Utility Analysis of Pembrolizumab Versus Chemotherapy as First-Line Treatment for Metastatic Non-Small Cell Lung Cancer With Different PD-L1 Expression Levels

To evaluate the cost–utility of pembrolizumab versus chemotherapy as the first-line setting for metastatic nonsmall cell lung cancer (NSCLC) from the US health care system perspective, a Markov model was developed to compare the lifetime cost and effectiveness of pembrolizumab versus chemotherapy for untreated metastatic NSCLC, based on the clinical data derived from phase III randomized controlled trial (KEYNOTE- 042; ClinicalTrials.gov; NCT02220894). Weibull distribution was fitted to simulate the parametric survival functions. Drug costs were collected from official websites, and utility values were obtained from published literature. Total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were computed as primary output indicators. The impact of different PD-L1 expression levels on ICER was also evaluated. One-way and probabilistic sensitivity analyses were performed to assess the model uncertainty. Compared with chemotherapy, patients treated with pembrolizumab provided an additional 1.13, 1.01, and 0.59 QALYs in patients with PD-L1 expression levels of ≥50%, ≥20%, and ≥1%, with corresponding incremental cost of $53,784, $47,479, and $39,827, respectively. The resultant ICERs of pembrolizumab versus chemotherapy were $47,596, $47,184, and $68,061/QALY, in three expression levels of PD-L1, respectively, all of which did not exceed the WTP threshold of 180,000/QALY. Probability sensitivity analysis outcome supported that pembrolizumab exhibited evident advantage over chemotherapy to be cost-effective. One-way sensitivity analysis found that ICERs were most sensitive to utility value of pembrolizumab in progression survival state. All the adjustment of parameters did not qualitatively change the result. For treatment-naive, metastatic NSCLC patients with PD-L1+, pembrolizumab was estimated to be cost-effective compared with chemotherapy for all PD-L1 expression levels at a WTP threshold of $180,000/QALY in the context of the US health care system.     

谷氨酸受体在左旋多巴诱导的异动症中的相关研究进展

在帕金森病(PD)患者中,长期使用左旋多巴而诱导的异动症(LID)显著影响着左旋多巴的疗效及患者的生活质量,现有的应对方案效果也均不甚理想,其原因与LID的机制目前尚未完全阐明密切相关。近年来越来越多的研究证实,谷氨酸能系统与多巴胺能系统紧密关联,谷氨酸受体在LID中的作用也日益凸显,特别是代谢型谷氨酸受体(mGluR)4、mGluR5以及部分离子型谷氨酸受体(iGluRs)在LID的机制研究和临床药物研究中更是关注热点。笔者现对各类谷氨酸受体在LID中的变化、作用以及相关的临床研究进展进行综述,以期为PD患者中LID的诊治和机制阐明提供新思路。     

组织细胞吞噬性脂膜炎一例

1例主诉为"反复皮疹2个月、发热1个月余"的患儿就诊于深圳市儿童医院,曾被误诊为"结节性脂膜炎",经过基因及病理检查修正诊断为组织细胞吞噬性脂膜炎。本病是一种罕见的特殊类型脂膜炎,易继发噬血细胞综合征,临床上误诊率及病死率极高。     

Prevalence of metabolic syndrome in patients with psoriasis: a cross-sectional study in Singapore

INTRODUCTIONPsoriasis is a chronic inflammatory condition that affects the skin and joints, and is associated with cardiovascular risk factors, including metabolic syndrome (MetS). We aimed to assess the prevalence of MetS in patients with psoriasis and determine whether there was a correlation between psoriasis severity and MetS in a Singapore population.METHODSThis was a cross-sectional study of patients with psoriasis, aged 18–69 years, who attended a tertiary dermatology referral centre in Singapore from October 2007 to February 2009. Fasting glucose, lipids, blood pressure, Psoriasis Area and Severity Index, and body mass index were measured. MetS was diagnosed in the presence of three or more criteria of the modified National Cholesterol Education Program Adult Treatment Panel III.RESULTSAmong 338 patients with psoriasis, there were 238 (70.4%) men and 100 (29.6%) women, who were Chinese (n = 228; 67.5%), Malay (n = 52; 15.4%) and Indian (n = 58; 17.2%). The prevalence of MetS was 45.1%. MetS was 44% more prevalent in patients older than 50 years (p = 0.02). Malay patients with psoriasis were significantly more likely to have hypertriglyceridaemia, elevated fasting plasma glucose and abdominal obesity. There was no significant correlation between psoriasis severity and risk of MetS.CONCLUSIONThe prevalence of MetS in patients with psoriasis in Singapore was 45.1%, or nearly threefold higher than the Singapore general population. Patients with psoriasis should be screened yearly for MetS and any modifiable cardiovascular risk factors should be actively controlled.     

MIR-140-5p affects chondrocyte proliferation,apoptosis, and inflammation by targeting HMGB1 in osteoarthritis

Inflammation Research - This study aimed to test the expression and biological function of miR-140-5p in osteoarthritis (OA), and identify its target gene and explore its mechanism in OA....     

伴双手麻木的结节性皮肤淀粉样变一例

患者男，53岁，因面部、双手、阴茎、臀部结节斑块5年就诊于福州市皮肤病防治院皮肤科。5年前无明显诱因患者前额出现数个粟粒至蚕豆大小结节，因无自觉症状，未予治疗。皮疹逐渐增多、增大，双上眼睑、鼻背、双手指、阴茎、臀部等部位逐渐出现类似皮疹，伴双手麻木感，呈阵发性，与天气冷热无关，无发热、四肢乏力、关节肿痛等不适，曾自行外用多种药膏（具体不详）无效。既往史及家族史无特殊，各系统检查未见明显异常……