pigenetic reprogramming in small cell lung cancer

Small cell lung cancer(SCLC),a highly lethal lung cancer sub-type with distinct neuroendocrine-like features,accounts for 10%–15%of all lung cancers.The overall 5-year survival rate remains less than 10%.SCLC is characterized by early metastasis,thus minimizing the potential patient benefits of surgery.In recent decades,the first-line treatment for SCLC has remained chemotherapy combining etoposide and cisplatin(E/P).Despite high rates of response to E/P treatment,SCLC eventually relapses and is almost universally resistant to treatment at recurrence,thus making SCLC a recalcitrant malignancy.Moreover,the limited knowledge regarding the molecular mechanisms underlying SCLC metastasis and resistance greatly hinders improvements in overall SCLC survival.To better understand the molecular mechanisms of SCLC and discover potential therapeutic targets,extensive efforts have continued for decades.

Analysis of the arginine biosynthetic gene cluster argCJBDFR of Corynebacterium crenatum

Objective: Corynebacterium crenatum AS1.542, a Gram-positive bacterium and indigenous nonpatho-genic corynebacteria, is widely exploited for the in-dustrial production of amino acids. The objective of this paper is to clarify the genetic information of the arginine biosynthetic pathway, and further more contribute to the improvement of arginine produc-tion. Methods: Polymerase chain reaction (PCR) technology was employed for obtaining the arginine biosynthetic gene sequence, and softwares eg. Laser-gene, BPROM, RNAshapes were used for the analysis of obtained sequences. Results: Arginine biosynethetic gene cluster of C. crenatum, comprising argJ, argB, argD, argF, argR and part of argC, has been ampli-fied and sequenced. The gene order has been estab-lished as argCJBDFR, with a entire length of 6.08kb. Conclusion: An internal promoter was found in the upstream of argB gene, four argBDFR ORFs are lo-cated in a same transcription unit, and the tran-scripiton termination of argC gene is irrelevant with the rho-factor. Comparison with ornithine acetyl-transferase (coded by argJ gene) from C. glutamate, ornithine acetyltransferase from C. crenatum also belongs to the monofunctional enzymes.

简易版色盲生活质量测评量表在红绿色盲中的信效度分析

目的:汉化色盲生活质量测评量表(CBQoL)生成中文版CBQoL,并根据中国文化背景调试整合为简易版CBQoL,分析简易版CBQoL的信效度及二者的相关性。方法:横断面调查研究。根据医疗研究中使用的量表跨文化调试指南,将CBQoL经前译、整合、回译、跨文化验证、专家委员会评定和预调查形成中文版及简易版CBQoL,包括健康与生活方式、情绪、职业,共3个维度。采用方便抽样法抽取于2022年6月至2023年11月在福建医科大学附属第二医院健康体检的红绿色盲患者50例进行中文版及简易版CBQoL的调查测试。采用Cronbach'sα系数和折半系数、重测信度相关分析、内容效度、结构效度对简易版CBQoL进行信效度分析,采用Spearman相关系数评价简易版CBQoL与中文版CBQoL的相关性。结果:简易版CBQoL的Cronbach'sα系数为0.83,折半系数为0.78,重测信度系数0.93。探索性因子分析提取3个公因子,累计方差贡献率为77.0%,结构效度良好。简易版CBQoL与中文版CBQoL的各维度评分及总分相关性分析均呈正相关关系(均P<0.05)。结论:简易版CBQoL不仅与中文版CBQoL评分具有良好的相关性,而且具有良好的信度和效度,可用于评估中文母语色盲者的生活质量。

Lea Symbols视力表在42~78个月儿童视力检查中的重复测量可信度分析

目的:探讨Lea Symbols视力表在学龄前儿童视力检查中的重复测量可信度。方法:横断面研究。2017年4-5月对泉州市泉港区实验幼儿园的250名42~78(61.9±10.3)个月的学龄前儿童进行全面的眼科检查,使用Lea Symbols视力表重复测量右、左眼的单眼远视力,采用LogMAR记录法记录视力值。采用Bland-Altman分析、加权Kappa检验、组内相关系数3种统计分析方法衡量2次测量之间的重复测量可信度。结果:3种分析方法均显示Lea Symbols视力表在学龄前儿童视力检查中的重复测量可信度较好,2次测量间视力的差值94.3%在1行以内,2次测量的视力值之间的相关性较高(r=0.753,P<0.001)。在139名屈光正常儿童中,2次测量的视力值(LogMAR)平均相差0.014。在139名屈光正常儿童中,视力与月龄的相关性是显著的,月龄越大视力越好(r第1次=-0.335,P<0.001;r第2次=-0.424,P<0.001);性别对可重复性没有影响(P=0.197)。结论:Lea Symbols视力表可用于中国42个月及以上学龄前儿童的视力检查,可以在临床视力检查中推广使用。

智能视障辅助器具适配体系研究进展

视力障碍人士需要各种视障辅助器具(简称视障辅具)进行补偿或代偿视觉, 同时接受视障辅具使用训练及定期功能评估以加强技能。目前, 社会机构服务模式、医院低视力门诊模式、流动诊所或项目服务模式等传统的视障辅具适配的康复治疗是有效的, 但受到地域、人才、科技、资源等方面的限制, 服务覆盖面有限, 尚未全面满足视障人士需求。远程、基于互联网的现代化视障辅具智能适配模式已被应用于临床中, 并发挥着重要的作用。现就智能视障辅助器具适配体系研究进展作一综述, 旨在为视障康复提供新的思路, 提高视障康复效率。

Epigenetic drug library screening identified an LSD1 inhibitor to target UTX-deficient cells for differentiation therapy

UTX(also known as KDM6A),a histone 3 lysine 27 demethylase,is among the most frequently mutated epigenetic regulators in myelodysplastic syndrome(MDS)and acute myeloid leukemia(AML).Recent studies have suggested that UTX mutations promote MDS and AML by blocking the differentiation of hematopoietic stem and progenitor cells(HSPCs).Here,we performed an epigenetic drug library screening for small molecules able to release the differentiation block on HSPCs induced by UTX deficiency.We found that SP2509,a selective inhibitor of LSD1,specifically promoted the differentiation of Utx-null HSPCs while sparing wild-type HSPCs.Transcriptome profiling showed that Utx loss reduced the expression of differentiation-related and tumor suppressor genes,correlating with their potential roles in HSPC self-renewal and leukemogenesis.In contrast,SP2509 treatment reversed these changes in gene expression in Utx-null HSPCs.Accordingly,Utx loss decreased H3K4 methylation level probably through the COMPASS-like complex,while LSD1 inhibition by SP2509 partially reversed the reduction of H3K4 methylation in Utx-deficient HSPCs.Further,SP2509 promoted the differentiation of Utx-null AML cells in vitro and in vivo and,therefore,extended the survival of these leukemic mice.Thus,our study identified a novel strategy to specifically target both premalignant and malignant cells with Utx deficiency for differentiation therapy and provided insights into the molecular mechanisms underlying the role of Utx in regulating HSPCs and related diseases.

Whole-exome sequencing of a multicenter cohort identifies genetic changes associated with clinical phenotypes in pediatric nephrotic syndrome

Understanding the association between the genetic and clinical phenotypes in children with nephrotic syndrome(NS)of different etiologies is critical for early clinical guidance.We employed whole-exome sequencing(WES)to detect monogenic causes of NS in a multicenter cohort of 637 patients.In this study,a genetic cause was identified in 30.0%of the idiopathic steroid-resistant nephrotic syndrome(SRNS)patients.Other than congenital nephrotic syndrome(CNS),there were no significant differences in the incidence of monogenic diseases based on the age at manifestation.Causative mutations were detected in 39.5%of patients with focal segmental glomerulosclerosis(FSGS)and 9.2%of those with minimal change disease(MCD).In terms of the patterns in patients with different types of steroid resistance,a single gene mutation was identified in 34.8%of patients with primary resistance,2.9%with secondary resistance,and 71.4%of children with multidrug resistance.Among the various intensified immunosuppressive therapies,tacrolimus(TAC)showed the highest response rate,with 49.7%of idiopathic SRNS patients achieving complete remission.Idiopathic SRNS patients with monogenic disease showed a similar multidrug resistance pattern,and only 31.4%of patients with monogenic disease achieved a partial remission on TAC.During an average 4.1-year follow-up,21.4%of idiopathic SRNS patients with monogenic disease progressed to end-stage renal disease(ESRD).Collectively,this study provides evidence that genetic testing is necessary for presumed steroid-resistant and idiopathic SRNS patients,especially those with primary and/or multidrug resistance.

Identifying a confused cell identity for esophageal squamous cell carcinoma

The cell identity of malignant cells and how they acquire it are fundamental for our understanding of cancer.Here,we report that esophageal squamous cell carcinoma(ESCC)cells display molecular features equally similar but distinct to all three types of normal esophageal epithelial cells,which we term as confused cell identity(CCI).CCI is an independent prognostic marker associated with poor prognosis in ESCC.Further,we identify tropomyosin 4(TPM4)as a critical CCI gene that promotes the aggressiveness of ESCC in vitro and in vivo.And TPM4 creates CCI through activating the Jak/STAT-SOX2 pathway.Thus,our study suggests an unrecognized feature of ESCC cells,which might be of value for clinic prognosis and potential interference.

A genomic association study revealing subphenotypes of childhood steroid-sensitive nephrotic syndrome in a larger genomic sequencing cohort

Dissecting the genetic components that contribute to the two main subphenotypes of steroid-sensitive nephrotic syndrome(SSNS)using genome-wide association studies(GWAS)strategy is important for understanding the disease.We conducted a multicenter cohort study(360 patients and 1835 controls)combined with a GWAS strategy to identify susceptibility var-iants associated with the following two subphenotypes of ssNS:steroid-sensitive nephrotic syn-drome without relapse(SSNswR,181 patients)and steroid-dependent/frequent relapse nephrotic syndrome(SDNS/FRNS,179 patients).The distribution of two single-nucleotide poly-morphisms(SNPs)in ANKRD36 and ALPG was significant between SSNSWR and healthy controls,and that of two SNPs in GAD1 and HLA-DQA1 was significant between SDNS/FRNS and healthy controls.Interestingly,rs1047989 in HLA-DQA1 was a candidate locus for SDNS/FRNS but not for SSNSWR.No significant SNPs were observed between SSNSWR and SDNS/FRNS.Meanwhile,chromosome 2:171713702 in GAD1 was associated with a greater steroid dose(>0.75 mg/kg/d)upon relapse to first remission in patients with SDNS/FRNS(odds ratio=3.14;95%confidence interval,0.97-9.87;P=0.034).rs117014418 in APOL4 was significantly associated with a decrease in eGFR of greater than 20%compared with the baseline in SDNS/FRNS patients(P=0.0001).Protein-protein intersection network construction suggested that HLA-DQA1 and HLA-DQB1 function together through GSDMA.Thus,SSNSWR belongs to non-HLA region-dependent nephropathy,and the HLA-DQA/DQB region is likely strongly associated with dis-ease relapse,especially in SDNS/FRNS.The study provides a novel approach for the GWAS strategy of SsNS and contributes to our understanding of the pathological mechanisms of SSNSWRandSDNS/FRNS.