Differential Expression of PD-L1 Between Sporadic and VHL-Associated Hereditary Clear-Cell Renal Cell Carcinoma and Its Correlation With Clinicopathological Features

Background

Programmed death ligand-1 (PD-L1) is a potential predictive biomarker for immunotherapy in several malignancies. However, the expression level and clinical significance of PD-L1 in von Hippel–Lindau (VHL)-associated hereditary clear-cell renal cell carcinoma (ccRCC) remain unclear.

Variant analysis and genotype/phenotype association study in 42 Chinese patients with Bartter syndrome type 3

Objective To analyze the variants of 42 Chinese patients with Bartter syndrome type 3 (BS3) and explore the characteristics of genotype and phenotype. Methods Forty-two genetically diagnosed patients from 40 Han and one Hui families were collected in the Affiliated Hospital of Qingdao University and the Affiliated Qingdao Municipal Hospital of Qingdao University during the period of June 2012 to October 2018. The second-generation sequencing and multiplex ligase probe-dependent amplification (MLPA) technique were used to analyze the CLCNKB gene variation and its characteristics in children with BS3. The clinical data were collected, and the therapeutic effect and growth improvement were observed and followed up. Thirty eight patients were divided into severe (n=26) and light (n=12) groups according to the severity of genetic variation. The clinical phenotypic characteristics of the two groups were compared. Results Thirty-six variants including 16 novel ones of CLCNKB gene were found. The whole gene deletion of CLCNKB gene was the most frequent mutation (40%), and the rate of large deletions was up to 55%. The most common symptoms included development retardation (38/42), polydipsia and polyuria (35/42), constipation (31/42) and vomiting (27/42). All patients presented with hypokalemia, hypochloremia and metabolic alkalosis. After the medicine treatment that based on indomethacin and potassium chloride, most patients could achieve obvious recovery of growth rate and restoration of hypokalemia. The severe group showed more severe metabolic alkalosis than the light group. Conclusions Thirty-six variants of CLCNKB gene have been found in this study, including 16 novel ones, which enrich the human gene mutation database (HGMD) and provide valuable references to diagnosis, treatment and the genetic counseling of Chinese population.     

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.     

A rare case of monozygotic triplets with Duchenne muscular dystrophy

Twins with Duchenne muscular dystrophy (DMD) have been widely studied. We report the first rare case of monozygotic triplets with DMD who shared consistent phenotypes, including delayed motor and language milestones, muscle wasting and weakness, joint contracture, and lumbar lordosis. Muscle magnetic resonance imaging and biopsy revealed the similar muscle injury characteristics and dystrophin absence. Short tandem repeat analysis confirmed monozygosity. A de novo mutation (exon 49–52 deletion) was found in the triplets but not in their mother. Treatment included prednisone, idebenone, and rehabilitation management. At the 2-year follow-up, motor function had deteriorated, and muscle fatty infiltration was more extensive and severe. Our case offers a unique opportunity for genetic and therapeutic research. Furthermore, it highlights the critical role of genetic factors in DMD phenotypes and provides a potential choice for treatment observations.     

Impact of Multifocality and Multilocation of Positive Surgical Margin After Radical Prostatectomy on Predicting Oncological Outcome

Objective

To assess the impact of focality and location of positive surgical margins (PSM) on long-term outcomes after radical prostatectomy (RP) for prostate cancer (PCa), including biochemical recurrence (BCR), metastasis and overall mortality.

浅谈现代化设备对血液成分制备工作的影响

随着近些年科学技术的不断进步,关于制备血液的设备也陆续出现,改变了以往靠人工制备血液的传统方式,不仅增加血液储备,同时也避免了血液的浪费,提升了血站的血液供应能力,可减少不良事件发生例数,使信息一体化,能够帮助血液成分制备工作顺利进行。该文将细致探讨现代化设备对血液成分制备工作的影响。     

Adoption of the 275-patient buprenorphine treatment waiver for treating opioid use disorder: A state-level longitudinal analysis

Abstract

Background: Increasing access to buprenorphine treatment is a critical tool for addressing the opioid epidemic in the United States. In 2016, a federal policy change allowed physicians who meet specific requirements to treat up to 275 concurrent buprenorphine patients. This study examines state-level measures of buprenorphine treatment supply over 21?months since this policy change and estimates associations between the supply of 275-patient waivers and state characteristics. Methods: Monthly state-level measures of the number of physicians holding the 275-patient waiver per 100,000 residents were constructed from September 2016 to May 2018 using the Drug Enforcement Agency’s Controlled Substance Act database. State characteristics were obtained from publicly available sources. Mixed-effects regression models were estimated to examine change over time. Results: During the 21-month period, the number of physicians waivered to treat 275 patients increased from 153 to 4009 physicians. The mean supply of 275-patient physicians per 100,000 state residents significantly increased from 0.07 (SD?=?0.21) in September 2016 to 1.43 (SD?=?1.08) in May 2018 (t?=??9.84, df?=?50, P?<?.001). The final mixed-effects regression model indicated that Census division and the preexisting supply of 100-patient waivered physicians were correlated with the rate of growth in 275-patient waivers over the study period. Conclusions: Although uptake of the 275-patient waiver has exceeded initial projections, growth is uneven across the United States. Unequal patterns of growth pose a challenge to efforts to increase treatment availability as a means of addressing the opioid epidemic.     

康复运动操联合牵引在老年腰椎间盘突出症患者中的应用效果研究

目的探讨康复运动操联合牵引在老年腰椎间盘突出症患者中的应用效果及对腰椎活动度的影响。 方法选择2018年10月至2019年9月老年腰椎间盘突出症患者86例作为对象，随机分为对照组（n=43例）和观察组（n=43例）。对照组采用常规牵引治疗，观察组在对照组基础上联合康复运动操治疗，4周治疗后对患者效果进行评估，比较两组视觉模拟疼痛（VAS）评分、炎症因子水平、腰椎活动度及满意度。 结果观察组治疗后1、2、3、4周VAS评分低于对照组（P<0.05）；观察组治疗后4周IL-1β、TNF-α及TXB2水平均低于对照组（P<0.05）；观察组治疗后4周前屈、后伸、侧屈均高于对照组（P<0.05）；观察组治疗后4周遵医治疗、康复运动、定期复查、治疗效果及治疗形式满意度均高于对照组（P<0.05）。 结论康复运动操联合牵引能减轻老年腰椎间盘突出症患者疼痛，提高患者腰椎活动度，且两种方法干预能降低机体炎症瀑布联级反应，提高患者治疗满意度，值得推广应用。     

A Review of Machine Learning Techniques for Keratoconus Detection and Refractive Surgery Screening

ABSTRACT

Various machine learning techniques have been developed for keratoconus detection and refractive surgery screening. These techniques utilize inputs from a range of corneal imaging devices and are built with automated decision trees, support vector machines, and various types of neural networks. In general, these techniques demonstrate very good differentiation of normal and keratoconic eyes, as well as good differentiation of normal and form fruste keratoconus. However, it is difficult to directly compare these studies, as keratoconus represents a wide spectrum of disease. More importantly, no public dataset exists for research purposes. Despite these challenges, machine learning in keratoconus detection and refractive surgery screening is a burgeoning field of study, with significant potential for continued advancement as imaging devices and techniques become more sophisticated.