期刊文献+
任意字段
题名或关键词
题名
关键词
摘要
作者
第一作者
机构
刊名
分类号
参考文献
作者简介
基金资助
栏目信息
共找到2,918篇文章
< 1 2 … 146 >
每页显示 20 50 100
已选0条
引用分析
参考文献
引证文献
 统计分析
检索结果
已选文献
显示方式：
Engineering Prime Editing System for Concurrent Gene Knockout and Point Mutation Induction (KAPSi) in Rice 认领 引用
1
作者 LIU Xiaoshuang MA Chong +5 位作者 WANG Dongmei XU Youshen QIN Ruiying LI Juan XU Rongfang WEI Pengcheng 《Rice science》 SCIE CAS CSCD 2026年第3期277-281,I0001-I0010,共5页
Precise manipulation of complex agronomic traits often requires the simultaneous introduction of mutations at multiple gene loci,a capability that remains challenging for existing genome-editing technologies.In this s... Precise manipulation of complex agronomic traits often requires the simultaneous introduction of mutations at multiple gene loci,a capability that remains challenging for existing genome-editing technologies.In this study,we developed and systematically compared five strategies for concurrent knockout and point mutation induction(KAPSi)based on prime editing,aiming to integrate precise nucleotide substitutions with efficient gene knockout within a single editing framework. 展开更多
关键词 manipulation complex agronomic traits prime editingaiming concurrent gene knockout introduction mutations editing framework prime editing integrate precise nucleotide substitutions concurrent knockout point mutation induction kapsi based
暂未订购 下载PDF
Emerging role of DNA polymerase epsilon non-exonuclease domain mutations in colorectal cancer:From sequence variants to clinical implications 认领 引用
2
作者 Jia-Ju Xu Chun-Xiao Ni Jia-Ju Xu 《World Journal of Gastroenterology》 SCIE CAS 2026年第6期7-14,共8页
This editorial highlights the emerging significance of non-exonuclease domain mutations(non-EDMs)in DNA polymerase epsilon(POLE)in colorectal cancer(CRC),inspired by the recent study by Taskiran et al.Their study reve... This editorial highlights the emerging significance of non-exonuclease domain mutations(non-EDMs)in DNA polymerase epsilon(POLE)in colorectal cancer(CRC),inspired by the recent study by Taskiran et al.Their study revealed an exceptionally high frequency of POLE mutations(53.65%)in a Turkish CRC cohort,primarily attributed to a specific frameshift variant(p.V1446fs3)with undetermined pathogenic significance.Notably,the non-EDMs showed significant co-occurrence with mutations in critical genes,such as MLH3,MSH3,KRAS,PIK3CA,and BRAF,implying a potential synergistic interaction between impaired DNA repair mechanisms and activation of oncogenic pathways.Although POLE-mutant tumors rarely display high microsatellite instability,their hypermutator phenotype may make them more responsive to immunotherapy.This commentary underscores the need for functional assays and validation through multi-center studies to establish the pathogenicity and clinical relevance of non-EDMs.Furthermore,it advocates for the incorporation of comprehensive POLE sequencing,including non-EDM regions,into standard molecular subtyping frameworks for CRC to refine personalized treatment strategies. 展开更多
关键词 DNA polymerase epsilon Colorectal cancer Non-exonuclease domain mutations Co-mutation Tumor mutational burden
暂未订购 下载PDF
Novel germline JAK2 L808W and E305Vfs*4 mutations in familial essential thrombocythemia:Evidence from two pedigrees 认领 引用
3
作者 Jianxin Liu Wenqing Hu +4 位作者 Chunjian Wang Yayun Zhang Min Ouyang Hanyun Ren Meixiang Zhang 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2026年第2期285-288,共4页
The classical Philadelphia chromosome-negative myeloproliferative neoplasms(MPNs),including polycythemia vera,essential thrombocythemia(ET),and primary myelofibrosis,are clonal hematopoietic disorders driven by somati... The classical Philadelphia chromosome-negative myeloproliferative neoplasms(MPNs),including polycythemia vera,essential thrombocythemia(ET),and primary myelofibrosis,are clonal hematopoietic disorders driven by somatic mutations in JAK2(most notably V617F),CALR,or MPL,all of which converge on constitutive activation of the JAK-STAT pathway(1).Triple-negative essential thrombocythemia(TN-ET)is a distinct subtype of ET,accounting for approximately 10%-20%of all ET cases.These cases lack MPN driver mutations but still exhibit histopathological and clinical features sufficient for the diagnosis of ET.A subset of TN-ET cases shows familial predisposition and is caused by germline mutations in JAK2 and MPL(2).Unlike the common somatic V617F mutation,these germline variants are often atypical,located outside classic mutational hotspots,and display variable penetrance(3). 展开更多
关键词 primary myelofibrosisare clonal hematopoietic disorders Jak E VFS mpn driver mutations Jak L W germline mutations familial essential thrombocythemia triple negative essential thrombocythemia
暂未订购 下载PDF
Rapid on-site genotyping of the ovine prolific FecBBmutation using a CRISPR/Cas12a-based detection system 认领 引用 被引量：2
4
作者 Tingjie Wu Jiayuan Sun +5 位作者 Lijin Lu Chen Wang Shiwei Zhou Yulin Chen Xinjie Wang Xiaolong Wang 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2026年第4期1597-1605,共9页
BMPR1B is a pivotal gene that influences reproductive performance in sheep.The sheep populations that carry the FecBBmutation within this gene exhibit significantly higher lambing rates compared to wild-type popula... BMPR1B is a pivotal gene that influences reproductive performance in sheep.The sheep populations that carry the FecBBmutation within this gene exhibit significantly higher lambing rates compared to wild-type populations.Therefore,screening for individuals carrying the FecBBmutation is crucial for effective sheep breeding programs.This study aims to establish a rapid,precise,and visualised on-site detection method for genotyping the prolific FecBBmutation in sheep.We combined the CRISPR/Cas12a system with the recombinase-polymerase amplification(RPA)technique.We introduced an additional nucleotide mismatch on the amplification primers to form a Cas12a-recognised protospacer adjacent motif(PAM)sequence.In addition,mismatches were introduced in CRISPR-derived RNA(crRNA)to enable naked-eye differentiation of the assay results.Subsequently,we validated the accuracy of the method by examining additional blood samples from 56 sheep representing four breeds.The results of using our developed system were highly consistent with the Sanger sequencing.Overall,the CRISPR/Cas12a-based detection provides a rapid and more versatitle method for FecBBgenotyping.It holds promise in enhancing efficiency in livestock breeding programmes for any single nucleotide mutations. 展开更多
关键词 CRISPR/Cas12a isothermal amplification SNP detection BMPR1B FecBBmutation sheep
暂未订购 下载PDF
Clinical spectrum and genotype-phenotype correlation of ABCB4 mutations in children:Insights from a North Indian cohort 认领 引用
5
作者 Chennakeshava Thunga Suvradeep Mitra +4 位作者 Alisha Babbar Raghav Lal Arnab Pal Nandita Kakkar Sadhna Bhasin Lal 《World Journal of Hepatology》 2026年第1期124-140,共17页
BACKGROUND Progressive familial intrahepatic cholestasis type 3,caused by mutations in the ABCB4 gene,is a rare genetic disorder.Although severe phenotypes due to biallelic mutations are well described,emerging data s... BACKGROUND Progressive familial intrahepatic cholestasis type 3,caused by mutations in the ABCB4 gene,is a rare genetic disorder.Although severe phenotypes due to biallelic mutations are well described,emerging data seem to suggest the clinical relevance of monoallelic variants.AIM To describe the clinical spectrum and genotype-phenotype correlation of ABCB4 mutations in children in a cohort of North Indian children.METHODS This is a retrospective analysis of a prospectively maintained database from a single tertiary care centre.Children(≤18 years)with ABCB4 mutations between January 2021 and March 2025 were analysed.The clinical presentation,laboratory investigations,genetic sequencing and outcomes were recorded.Patients were stratified into group 1(homozygous/compound heterozygous)and group 2(heterozygous).Variant pathogenicity was assessed using the American College of Medical Genetics guidelines and available predictive tools.RESULTS Of the 26 patients,16 had biallelic mutations,and 10 had monoallelic mutations.Group 1 exhibited higher rates of positive family history(75%vs 30%,P=0.04),ascites(43.2%vs 0%,P=0.02),larger varices(40%vs 0%,P=0.009),higher gamma glutamyl transferase levels(171 U/L vs 38 U/L,P=0.007),and lower platelet counts(162×109/L vs 415×109/L,P=0.007).Notably,two-thirds of patients in group 1 experienced disease progression,and one-third died during follow-up.Certain missense variants(e.g.,c.2860T>C)and all nonsense variants were linked to rapid deterioration.Most children in group 2 had transient cholestasis with a good outcome,but two older children succumbed.CONCLUSION Mutations in the ABCB4 gene contribute significantly to pediatric chronic liver disease.Patients with severe biallelic mutations frequently experience a progressive disease course,whereas those with monoallelic mutations may progress slowly.Genetic testing for ABCB4 should be considered in children with cryptogenic chronic liver disease,especially those with high gamma-glutamyltransferase cholestasis and portal hypertension. 展开更多
关键词 ABCB4 Monoallelic mutation Biallelic mutation Progressive familial intrahepatic cholestasis type 3 Chronic liver disease Decompensation End-stage liver disease Portal hypertension Sclerosing cholangitis
暂未订购 下载PDF
Letter to the Editor:Not one disease-ethnic-specific mutational pathways redefine precision oncology in esophageal cancer 认领 引用
6
作者 Rui-Jie Ming Hua-Wen Liu 《World Journal of Gastroenterology》 SCIE CAS 2026年第27期173-175,共3页
Precision oncology in esophageal squamous cell carcinoma has long operated under the implicit assumption that it is a single biological entity.In a study published in the World Journal of Gastroenterology,Wei et al pr... Precision oncology in esophageal squamous cell carcinoma has long operated under the implicit assumption that it is a single biological entity.In a study published in the World Journal of Gastroenterology,Wei et al provide a compelling and definitive challenge to this monolithic view.Through whole-exome sequencing of Han and Kazakh populations,they revealed not just different driver genes,but fundamentally distinct carcinogenic processes:A predominance of the apolipoprotein B messenger RNA-editing enzyme catalytic polypeptide-related mutational signatures in the Han cohort vs signatures of defective DNA mismatch repair in the Kazakh group.This finding transcends descriptive genomics;it suggests that esophageal squamous cell carcinoma in these populations may represent two different diseases at the molecular level.Clinically,this has profound implications.It questions the global applicability of clinical trial data derived from homogeneous populations and argues for the urgent need to incorporate ethnic diversity into genomic databases and trial design.Most provocatively,the authors uncover a crucial paradox:The Kazakh cohort,despite having poorer historical survival,exhibits a higher tumor mutational burden,a biomarker that paradoxically suggests the potential for heightened sensitivity to immune checkpoint inhibitors.This study is therefore a landmark,shifting the paradigm from treating a single cancer type to tailoring therapy based on distinct,ethnic-specific mutational etiologies. 展开更多
关键词 Esophageal squamous cell carcinoma Ethnic genomics Mutational signatures Precision oncology Tumor mutational burden Health equity
暂未订购 下载PDF
A novel A-to-G mutation in circBDP1 alters adipocyte proliferation and differentiation and affects bovine carcass traits 认领 引用
7
作者 Enhui JIANG Chiyuan ZHANG +7 位作者 Zhuoyuan HE Yuli ZHANG Yuta YANG Chuanying PAN Fugui JIANG Enliang SONG Sihuan ZHANG Xianyong LAN 《Journal of Zhejiang University-SCIENCE B》 SCIE CAS CSCD 2026年第8期918-922,I0024-I0032,共5页
Fat deposition in cattle,influenced by factors such as genetics,age,sex,and nutrition,plays a crucial role in determining growth rates,beef yield,and meat quality.Among these,genetics is the predominant factor(Kim et ... Fat deposition in cattle,influenced by factors such as genetics,age,sex,and nutrition,plays a crucial role in determining growth rates,beef yield,and meat quality.Among these,genetics is the predominant factor(Kim et al.,2020;Xing et al.,2025).Research in-dicates a high heritability for visceral(36%)and sub-cutaneous(57%)fat(Fox et al.,2012).Gene muta-tions that affect adipocyte function are significant con-tributors to variations in fat deposition and meat quality(Mannen,2011;Mwangi et al.,2019;Sun et al.,2023;Dementieva et al.,2024).Therefore,investigat-ing genetic variations in fat-related genes is essential for enhancing cattle performance. 展开更多
关键词 circbdp adipocyte function novel mutation carcass traits fat deposition adipocyte proliferation genetics adipocyte differentiation
暂未订购 下载PDF
Kdf1 missense mutation caused enamel defects by disrupting cell adhesion and Hippo-YAP signaling in dental epithelium 认领 引用
8
作者 Pei Li Runling Zeng +6 位作者 Jingyan Xue Yaling Song Jie Wu Binghui Zeng Ling Lin Dongsheng Yu Wei Zhao 《International Journal of Oral Science》 SCIE CAS CSCD 2026年第3期561-572,共12页
Amelogenesis imperfecta is a hereditary enamel defect arising from dental epithelium dysfunction.Although keratinocyte differentiation factor 1(KDF1)acts as an intracellular regulator in epithelial cells,the underlyin... Amelogenesis imperfecta is a hereditary enamel defect arising from dental epithelium dysfunction.Although keratinocyte differentiation factor 1(KDF1)acts as an intracellular regulator in epithelial cells,the underlying disease mechanism of the patient-derived KDF1 missense mutation in amelogenesis remains unclear.Here,we show that a patient-derived KDF1 mutation(c.908 G>C,p.R303P)causes enamel defects by disrupting cell adhesion and Hippo-YAP signaling.Immunohistochemistry revealed strong KDF1 expression throughout dental epithelium development,particularly at the cell membrane.Kdf1 mutation knock-in heterozygotes and homozygotes displayed graded defective enamel with reduced thickness,inadequate mineralization and disorganized microstructure.This phenotype correlated with a gradual reduction in enamel matrix proteins and proteases across genotypes.Bulk RNA sequencing of ameloblasts suggested marked changes in adhesion-related genes and the Hippo-YAP pathway.We characterized cellular consequences of this variant using both LS8 and ALC cell lines,which appeared abnormalities including accelerated proliferation,undermined differentiation,weakened adhesion,and enhanced migration.In vivo and in vitro findings supported a model wherein the KDF1 mutation impaired intercellular and cell-matrix adhesion in ameloblasts.As a result,ameloblast differentiation was hampered through excessive nuclear yes-associated protein(YAP)accumulation and overactivation of downstream proliferative genes.Pharmacological blockade of YAP and TEA domain family member 1(TEAD1)interaction rescued the mutant phenotypes.Taken together,Kdf1 mutation compromised murine amelogenesis through adhesion defects and subsequent Hippo-YAP dysregulation. 展开更多
关键词 epithelial cellsthe intracellular regulator dental epithelium dysfunctionalthough enamel defect keratinocyte differentiation factor amelogenesis imperfecta KDF mutation
暂未订购 下载PDF
Integrative multi-omic analysis identified ERBB2 mutations and senescence-driven immune suppression as dual therapeutic targets in LAR triple-negative breast cancer 认领 引用
9
作者 Yaxin Zhao Han Wang +3 位作者 Ying Wang Yizhou Jiang Xin Hu Zhiming Shao 《Cancer Biology & Medicine》 SCIE CAS CSCD 2026年第3期374-391,共18页
Objective:The luminal androgen receptor(LAR)subtype of triple-negative breast cancer(TNBC)differentiation displays low proliferation yet strong metastatic potential and a poor chemotherapy response.This study aimed to... Objective:The luminal androgen receptor(LAR)subtype of triple-negative breast cancer(TNBC)differentiation displays low proliferation yet strong metastatic potential and a poor chemotherapy response.This study aimed to define the molecular basis of the LAR subtype and identify actionable therapeutic targets.Methods:Comprehensive multi-omic analyses were performed on the FUSCC-TNBC cohort,integrating whole-exome sequencing,RNA sequencing,and functional validation in vitro and in vivo.Somatic mutation profiling,gene set enrichment analysis(GSEA),and weighted gene co-expression network analysis(WGCNA)were used to define genomic and transcriptomic signatures.A machine learning model using the Mime1 package was applied to derive a senescence-associated prognostic signature(LAR-S)and validation in external cohorts.Immune deconvolution was performed to decipher the tumor microenvironment.Functional assays,patient-derived organoids(PDOs),and TS/V mouse models were used to evaluate therapeutic responses to senescence-modulating agent and immunotherapy combinations.Results:The LAR subtype was enriched for PIK3CA,PTEN,and ERBB2 kinase domain mutations.Functional studies confirmed ERBB2 variants(e.g.,V777L and E698_P699delinsA)as oncogenic drivers conferring sensitivity to neratinib.Transcriptomic analyses revealed a dominant cellular senescence program associated with immune suppression.The LAR-S signature stratified survival across cohorts and predicted immunotherapy resistance.Targeting cellular senescence inhibited LAR subtype organoid growth and when combined with anti-PD-1 therapy synergistically suppressed tumor growth in vivo.Conclusions:The LAR subtype harbors two therapeutic vulnerabilities:ERBB2 mutation-driven kinase activation;and senescencemediated immune evasion.The LAR-S signature enables precise patient stratification and supports senescence-targeted and immunotherapy combination strategies as promising approaches for this refractory TNBC subtype. 展开更多
关键词 Triple-negative breast cancer luminal androgen receptor subtype ERBB2 mutation cellular senescence immunotherapy resistance
暂未订购 下载PDF
Enriched NKX2-1 Mutations in Bronchiolar Adenoma Variants:Evidence for Malignant Transformation or an Indolent Entity 认领 引用
10
作者 Lu-yao Li Gong-ming Dong +4 位作者 Yi-xin Ma Jie Liu Yan Shi Fu-quan Jia Guan-jun Zhang 《Current Medical Science》 SCIE CAS CSCD 2026年第1期116-130,共15页
Objective Bronchiolar adenoma(BA)is a peripheral pulmonary neoplasm characterized by a bilayered cell structure com-posed of basal cells and luminal cells.Owing to its low incidence and limited research data,clinician... Objective Bronchiolar adenoma(BA)is a peripheral pulmonary neoplasm characterized by a bilayered cell structure com-posed of basal cells and luminal cells.Owing to its low incidence and limited research data,clinicians and pathologists still have an insufficient understanding of this disease.This study aims to characterize the morphological,immunohistochemical,and genetic features of BA and its variants,and to determine whether BA can progress to a malignancy.Methods Among these 33 cases,21 were histologically characterized by double-layered tumors with continuous basal cell layers.Six patients exhibited a partial classic bilayer,transitioning from a bilayer to a monolayer in certain lesion areas(mixed-type BAs).Six other BA-like tumors with monolayered components might represent the early stage of malignant transformation of BA.Next-generation sequencing analysis was conducted on 33 cases to elucidate the genetic spectrum.Results All the cellular components exhibited a relatively mild morphology.Immunohistochemical analysis revealed that basal cells coexpressed p40 and cytokeratin 5/6.Thyroid transcription factor 1 was expressed in the double-cell layer,which consists of ciliated columnar epithelial cells,basal cells,nonciliated columnar epithelial cells,and cuboidal epithelial cells.The pan-cancer gene panel was used to observe driver alterations in 9 of 21 classic bilayered BAs(43%),2 of 6 mixed-type BAs(33%),and 3 of 6 monolayered BA-like lesions(50%).Genetically,monolayered BA-like lesions shared some alterations with classic BAs in mutational signatures,whereas NKX2-1 mutations were enriched only in monolayered BA-like lesions.Conclusion These findings underscore the histopathological and genetic characteristics of BA and its variants,suggesting that monolayered BA-like lesions have the potential to develop into lung adenocarcinoma.In the future,more cases should be recruited to further explore the malignant transformation of this specific entity via the multidimensional spectrum. 展开更多
关键词 Bronchiolar adenoma Monolayered BA-like lesions Histopathology Genomic analysis NKX2-1 mutation Lung adenocarcinoma Next-generation sequencing TTF-1
暂未订购 下载PDF
Expert consensus on the detection and clinical application of tumor mutational burden 认领 引用
11
作者 Zhenying Guo Chunwei Xu +168 位作者 Shirong Zhang Yue Hao Xiaotong Hu Ming Zhao Chan Xiang Yingshi Piao Pingli Sun Xueping Xiang Jing Zhao Huanwen Wu Weixing Li Jinpu Yu Jingping Yuan Shuangshuang Wang Cong Wang Yun Gu Bingjian Lv Liping Zhang Yueping Liu Xiaobin Cui Weizhong Gu Yining Li Wei Wang Wenjun Yang Weiguo Long Jingjing Xiang Hong Mou Biao Liu Huajuan Ruan Yubin Wang Yongjie Zhu Feng Wang Zhonghua Wang Xiaomin Feng Xing Liu Peng Li Min Deng Bin Lian Lili Mao Qian Wang Wenxian Wang Zhengbo Song Ziming Li Wenzhao Zhong Zhijie Wang Shengxiang Ren Wenfeng Fang Yongchang Zhang Jingjing Liu Xiuyu Cai Anwen Liu Wen Li Ping Zhan Hongbing Liu Tangfeng Lv Liyun Miao Lingfeng Min Yu Chen Yu Zhang Feng Wang Zhansheng Jiang Gen Lin Long Huang Xingxiang Pu Rongbo Lin Weifeng Liu Chuangzhou Rao Dongqing Lv Zongyang Yu Peng Shen Xiaoyan Li Chuanhao Tang Chengzhi Zhou Junping Zhang Junli Xue Hui Guo Qian Chu Rui Meng Jingxun Wu Rui Zhang Jin Zhou Zhengfei Zhu Yongheng Li Hong Qiu Fan Xia Yuanyuan Lu Xiaofeng Chen Rui Ge Enyong Dai Yu Han Jian Zhang Yinghua Ji Xianbin Liang Hongmei Zhang Xuelei Ma Xuewen Liu Yu Yao Peng Luo Weiwei Pan Fei Pang Fan Wu Dejian Gu Li Wang Liping Wang Youcai Zhu Li Lin Weiwen Li Xinqing Lin Jing Cai Ling Xu Jisheng Li Xiaodong Jiao Kainan Li Jia Wei Huijing Feng Lin Wang Yingying Du Wang Yao Xuefei Shi Xiaomin Niu Dongmei Yuan Yanwen Yao Yinbin Zhang Binbin Song Wenfeng Li Jianfei Fu Hong Wang Mingxiang Ye Dong Wang Zhaofeng Wang Qing Ji Yuan Fang Qing Wei Zhen Wang Bin Wan Donglai Lv Xiaofeng Li Shengjie Yang Jing Kang Jiatao Zhang Chao Zhang Lin Shi Yina Wang Bihui Li Zhang Zhang Ke Wang Zhefeng Liu Nong Yang Lin Wu Xiaobing Chen Gu Jin Zhongwu Li Miao Li Guansong Wang Jiandong Wang Meiyu Fang Yong Fang Xiaojia Wang Jing Chen Yiping Zhang Xixu Zhu Yi Shen Shenglin Ma Biyun Wang Lu Si Yong Song Yuanzhi Lu Aijun Liu Yuchen Han 《Cancer Biology & Medicine》 SCIE CAS CSCD 2026年第2期218-246,共29页
As an emerging biomarker,tumor mutational burden(TMB)has attracted increasing attention from clinicians in predicting the efficacy of tumor immunotherapy.Currently,TMB is detected primarily by whole-exome sequencing o... As an emerging biomarker,tumor mutational burden(TMB)has attracted increasing attention from clinicians in predicting the efficacy of tumor immunotherapy.Currently,TMB is detected primarily by whole-exome sequencing or targeted panel sequencing on high-throughput sequencing platforms.However,the lack of uniformity in detection methods,threshold settings,and reporting formats,as well as the significant differences in TMB values among different cancer types,have hindered the standardized application of this biomarker in clinical practice.This consensus focuses on the definition,standardization of detection,clinical significance,and limitations of TMB,and provides consensus recommendations for the clinical application of TMB in real-world practice in China.This consensus is aimed at helping clinicians and laboratory personnel understand the clinical significance and testing standards of TMB,promoting more accurate interpretation of test results,and improving patient care. 展开更多
关键词 Biomarkers tumor mutational burden tumor immunotherapy targeted panel sequencing whole-exome sequencing
暂未订购 下载PDF
Rabson-Mendenhall syndrome caused by a novel splice-site mutation(c.1123+2 T>C)of insulin receptor:A case report and review of literature 认领 引用
12
作者 Kun Wang Juan Zheng +4 位作者 Long-Chao Gu Rong-Rong Li Xu-Dong Su Jie Bai Lin Liao 《World Journal of Diabetes》 SCIE 2026年第1期211-220,共10页
BACKGROUND Rabson-Mendenhall syndrome(RMS)is an extremely rare monogenic form of diabetes caused by mutations in the insulin receptor(INSR)gene,with only about 50 cases reported worldwide to date.Here,we report a case... BACKGROUND Rabson-Mendenhall syndrome(RMS)is an extremely rare monogenic form of diabetes caused by mutations in the insulin receptor(INSR)gene,with only about 50 cases reported worldwide to date.Here,we report a case of RMS caused by a previously unreported c.1123+2 T>C splice mutation.CASE SUMMARY The patient was diagnosed with acanthosis nigricans and hypertrichosis at birth,and the growth rate was slower than that of normal children.At age 5,the patient had severe hyperinsulinemia,congenital heart abnormalities,and pineal cysts.At age 13,he was diagnosed with diabetes and exhibited symptoms of hyperinsulinemia,low body weight,growth retardation,acanthosis nigricans,dental anomalies,an oversized penis,and a pineal cyst.Sequencing results indicated an INSR c.1123+2 T>C mutation,and bioinformatic analysis suggested that this mutation led to splicing abnormalities,thereby affecting INSR function.Both parents carried the mutated gene,whereas his brother had a normal genotype.CONCLUSION Genetic diagnosis is vital in RMS;c.1123+2 T>C mutation of INSR causes pancreatic decline;current treatments show limited effectiveness. 展开更多
关键词 Rabson-Mendenhall syndrome Insulin receptor gene Splice mutation Hyperinsulinemia Case report
暂未订购 下载PDF
Impact of Germline BRCA1/2 Mutations on Clinical Outcomes in Metastatic Triple-Negative Breast Cancer Patients Treated with Sacituzumab Govitecan—An International CEBCC Study from Poland,the Czech Republic and Slovakia 认领 引用
13
作者 Renata Pacholczak-Madej Mirosława Püsküllüoğlu +24 位作者 Anna Polakiewicz-Gilowska Małgorzata Pieniążek Iveta Kolářová Miroslava Malejčíková Lenka Rušinová MilošHolánek Renata Soumarová Karolina Winsko-Szczęsnowicz JustynaŻubrowska Aleksandra Konieczna Agnieszka Młodzińska Daniel Krejčí Iwona Danielewicz Magdalena Szymanik-Resko Tomasz Ciszewski Maja Lisik-Habib Anika Pękala HanaŠtudentová JanŠustr Bogumiła Czartoryska-Arłukowicz AleksandraŁacko Jolanta Smok-Kalwat MichałJarząb Zuzana Bielčiková Marcin Kubeczko 《Oncology Research》 SCIE 2026年第6期457-470,共14页
Background:Germline breast cancer susceptibility gene 1/2(BRCA1/2)variants guide breast cancer treatment,but their clinical relevance in metastatic triple-negative breast cancer(mTNBC)treated with sacituzumab goviteca... Background:Germline breast cancer susceptibility gene 1/2(BRCA1/2)variants guide breast cancer treatment,but their clinical relevance in metastatic triple-negative breast cancer(mTNBC)treated with sacituzumab govitecan(SG)remains unclear.The study aimed to evaluate the association between BRCA status and outcomes in SG-treated mTNBC.Methods:We retrospectively analyzed 264 patients with mTNBC and known germline BRCA1/2(gBRCA1/2)status who received SG between August 2021 and May 2025 across multiple oncology centers in Poland,the Czech Republic and Slovakia.Survival outcomes were compared between patients with gBRCA1/2 mutations(gBRCA1/2m)and those with gBRCA1/2 wild-type(gBRCA1/2wt)using Kaplan–Meier estimates,the log-rank test,and multivariable Cox proportional hazards models.Two-sided p<0.05 was considered statistically significant.Results:Among 264 patients,35(13.3%)were gBRCA1/2m and 229(86.7%)were gBRCA1/2wt.After a median follow-up of 9.9 months,the median progression-free survival(PFS)was 4.5 months(95%confidence interval[CI]2.1–6.3)in gBRCA1/2 carriers versus 4.2 months(95%CI 3.5–5.8)in gBRCA1/2wt patients(p=0.10).Median overall survival(OS)was 9.1 months(95%CI 5.0–15.1)in gBRCA1/2 carriers compared to 11.5 months(95%CI 10.3–13.5)in gBRCA1/2wt patients(p=0.26).Brain metastases were more frequent in carriers(20%vs.8.3%,p=0.06).In multivariable analysis,Eastern Cooperative Oncology Group(ECOG)performance status was the only independent predictor of poorer survival(hazard ratio 1.97,95%CI 1.42–2.74,p<0.01),while gBRCA1/2 status showed no independent association.Conclusions:In this large retrospective cohort of mTNBC patients treated with SG,the presence of gBRCA1/2 was not associated with statistically significant differences in PFS or OS. 展开更多
关键词 Triple-negative breast cancer sacituzumab govitecan BRCA1/2 germline mutations real-world evidence international multicenter cohort
暂未订购 下载PDF
Letter to the Editor:From colorectal to pan-gastrointestinal cancer:Unlocking the therapeutic potential of DNA polymerase epsilon mutations 认领 引用
14
作者 Ling-Feng Zou Sui-Qi Yang +1 位作者 Shao-Ding Yu Cheng-Long Wang 《World Journal of Gastroenterology》 SCIE CAS 2026年第29期150-154,共5页
A recent investigation by Taskiran et al published in the World Journal of Gastroenterology on DNA polymerase epsilon(POLE)mutations in colorectal cancer prompted a broader discussion on the role of pathogenic variant... A recent investigation by Taskiran et al published in the World Journal of Gastroenterology on DNA polymerase epsilon(POLE)mutations in colorectal cancer prompted a broader discussion on the role of pathogenic variants as pangastrointestinal therapeutic biomarkers.Pathogenic exonuclease domain mutations(EDMs)in POLE have been identified in other digestive system malignancies including gastric,pancreatic,biliary,and hepatocellular carcinomas.Although rare,POLE EDMs consistently confer a hypermutator phenotype and high tumor mutational burden,irrespective of the tissue of origin.This shared biological consequence serves as a powerful predictor of response to immune checkpoint inhibitors,offering a vital,tissue-agnostic therapeutic option for patients with advanced or refractory diseases with established tumor mutational burden-high approvals.Therefore,to ensure that these rare but highly actionable opportunities are not missed,broader implementation of comprehensive genomic profiling,including POLE analysis,is warranted for all patients with advanced pan-gastrointestinal cancers. 展开更多
关键词 DNA polymerase epsilon Pan-gastrointestinal cancer Immune checkpoint inhibitors Tumor mutational burden Biomarker Mismatch repair deficiency
暂未订购 下载PDF
Optic neuropathy arising from the synergy between YARS2 and mitochondrial COX1 mutations 认领 引用
15
作者 Huiying Li Cheng Ai +5 位作者 Xiaofen Jin Jing Wang Jun Yu Yinglong Gao Douglas CWallace Min-Xin Guan 《Journal of Genetics and Genomics》 SCIE CAS CSCD 2026年第7期1266-1282,共17页
Leber hereditary optic neuropathy(LHON)is a paradigm for mitochondrial retinopathy.Here,we investigate the mechanism underlying the interaction between nuclear modifier and mtDNA mutation(s)that manifests optic neurop... Leber hereditary optic neuropathy(LHON)is a paradigm for mitochondrial retinopathy.Here,we investigate the mechanism underlying the interaction between nuclear modifier and mtDNA mutation(s)that manifests optic neuropathy in vivo to develop an effective therapeutic approach for this disease,using mouse models bearing LHON-linked Yars2G186V or COIV421A mutation alone and double mutations.Yars2G186V alters mitochondrial translation and assembly and activities of complex Ⅰ,Ⅲ,and Ⅳ,while COIV421A reduces complex Ⅳ activity.However,a single Yars2G186V orCOIV421A mutation causes mild declines in ATP production and yields relatively mild degeneration of retinal ganglion cells(RGCs).Notably,the synergy between COIV421A and Yars2G186V mutations aggravates mitochondrial dysfunction and oxidative stress.Interestingly,COIV421A mainly promotes apoptosis,and Yars2G186V contributes to ferroptosis.The combination of two mutations accelerates the degeneration of RGCs and photoreceptors.Strikingly,AAV-mediated Yars2 expression in the mouse retina carrying both Yars2G186V and COIV421A mutations corrects the defective translation and ferroptosis arising from the Yars2G186V mutation and remarkably improves mitochondrial function and causes morphologic and functional recovery of RGCs and photoreceptors.These findings provide mechanistic insights into the pathophysiology of LHON arising from nuclear modifiers and mtDNA mutation(s)and potential therapeutic strategies for LHON and other mitochondrial diseases. 展开更多
关键词 Optic neuropathy Mitochondrial DNA mutation Mitochondrial tyrosyl-tRNA synthetase Oxidative phosphorylation Ferroptosis Apoptosis Gene therapy
暂未订购 下载PDF
Multimodal artificial intelligence predicts PIK3CA mutation in breast cancer from digital pathology and clinical data:a multicenter study 认领 引用
16
作者 Jiaxian Miao Qi Liu +11 位作者 Jianing Zhao Shishun Fan Shenwen Wang Feng Ye Si Wu Jinze Li Huirui Zhang Meng Zhang Hong Bu Xiao Han Lianghong Teng Yueping Liu 《Cancer Biology & Medicine》 SCIE CAS CSCD 2026年第3期430-450,共21页
Objective:Accurate detection of PIK3CA mutations is essential for guiding PI3K-targeted therapies in breast cancer,yet sequencing is not universally accessible,and single-modality prediction models have limited perfor... Objective:Accurate detection of PIK3CA mutations is essential for guiding PI3K-targeted therapies in breast cancer,yet sequencing is not universally accessible,and single-modality prediction models have limited performance.This study developed a multimodal deep learning framework integrating whole-slide imaging(WSI)and structured clinical data to improve mutation prediction.Methods:A total of 1,047 patients from TCGA and 166 patients from 3 external centers were included.The histopathology model used a transformer-based pretrained encoder(H-optimus-0)and a clustering-constrained attention multiple instance learning(CLAM-SB MIL)classifier to generate WSI-level representations.The clinical model incorporated engineered clinical variables and an extreme gradient boosting(XGBoost)model.A decision-level late fusion strategy(Multimodal PIK3CA Model,MPM)combined probabilistic outputs from both branches.Performance was evaluated with the area under the curve(AUC)and secondary metrics.Interpretability was assessed via attention heatmaps and shapley additive explanations(SHAP)analysis.Results:MPM outperformed single-modality models.It achieved an AUC of 0.745 on TCGA and maintained stable performance across external cohorts(0.695,0.690,and 0.680).SHAP analysis identified molecular subtype as the most influential clinical feature,whereas attention maps highlighted mutation-associated morphological regions.Conclusions:The developed multimodal framework effectively integrates complementary morphological and clinical information,and provides a robust and generalizable method for predicting PIK3CA mutation status.Strong multicenter adaptability and biological interpretability support its potential use as a clinical decision-support tool and an accessible alternative to molecular testing. 展开更多
关键词 Breast cancer PIK3CA mutation multimodal artificial intelligence whole-slide imaging computational pathology
暂未订购 下载PDF
Independent prognostic value of KRAS mutation in resected colorectal cancer based on multi-gene sequencing 认领 引用
17
作者 Sheng-Qiang Zhao Zhao-Feng Luo +2 位作者 Zhan-Feng Yang Wei-Shan Zhang Yu-Ming Fu 《World Journal of Gastrointestinal Oncology》 SCIE 2026年第6期125-140,共16页
BACKGROUND Colorectal cancer(CRC)shows marked molecular heterogeneity,yet the clinicopathological and prognostic utility of routinely tested driver mutations in resected CRC remains incompletely defined.AIM To evaluat... BACKGROUND Colorectal cancer(CRC)shows marked molecular heterogeneity,yet the clinicopathological and prognostic utility of routinely tested driver mutations in resected CRC remains incompletely defined.AIM To evaluate the associations of KRAS,PIK3CA,FBXW7,and TP53 mutations with clinicopathological features and overall survival(OS)in patients with curatively resected CRC.METHODS We retrospectively analyzed 87 patients who underwent curative-intent CRC resection(2015-2020).Mutations in KRAS,PIK3CA,FBXW7,and TP53 were assessed using next-generation sequencing on formalin-fixed,paraffin-embedded tumor samples.Associations with clinicopathological variables were tested using appropriate categorical/continuous analyses.OS was evaluated by Kaplan-Meier/log-rank methods and Cox regression.Median follow-up was 60 months(cutoff:April 2025).RESULTS Mutation frequencies were KRAS of 44.8%,PIK3CA of 13.8%,FBXW7 of 27.6%,and TP53 of 64.4%.KRAS mutation clustered with adverse phenotypes(including perineural invasion,nodal/distant metastasis,multifocality,larger tumor size,and elevated tumor markers).PIK3CA mutation correlated with larger tumor diameter,while FBXW7 and TP53 showed selective clinicopathological associations.The 3-year and 5-year OS rates were 63.2%and 41.4%,respectively.KRAS mutation independently predicted worse OS(hazard ratio=3.57),whereas PIK3CA mutation showed a protective association(hazard ratio=0.26);FBXW7 and TP53 were not independent prognostic factors.CONCLUSION In resected CRC,KRAS mutation delineates a high-risk subgroup with inferior survival,supporting routine KRAS genotyping to enhance postoperative risk stratification and surveillance planning;larger,prospectively profiled cohorts are warranted to refine multi-gene prognostic models. 展开更多
关键词 Colorectal cancer Gene mutation KRAS TP53 Prognosis
暂未订购 下载PDF
Integrative analytical and statistical framework for optimization of multiplex qPCR detection of TGFBI mutations in refractive surgery candidates 认领 引用
18
作者 Yunfeng GU Liping MAO +7 位作者 Xiaoling LI Kangxuan SUN Qiuruo JIANG Wenhui WU Yangyang SHEN Shihao CHEN Meiqin ZHENG Yi XU 《Journal of Zhejiang University-SCIENCE B》 SCIE CAS CSCD 2026年第6期645-655,I0019-I0026,共11页
Refractive surgery can unmask or accelerate transforming growth factor-β-induced(TGFBI)-related corneal dystrophies that are undetectable by routine slit-lamp examination,creating a clear need for a rapid,standardize... Refractive surgery can unmask or accelerate transforming growth factor-β-induced(TGFBI)-related corneal dystrophies that are undetectable by routine slit-lamp examination,creating a clear need for a rapid,standardized,preoperative genetic screening.We developed a multiplex,allele-specific real-time quantitative polymerase chain reaction(qPCR)panel targeting five high-frequency TGFBI hotspots(R124C/L/H,R555W/Q)and built a statistics-driven analytical framework to optimize assay decisions.Receiver operating characteristic(ROC)analysis defined locus-specific cycle threshold(CT)cut-offs that were harmonized to a single decision threshold(CT=36)to simplify deployment.Analytical sensitivity was established by Probit modeling of serial two-fold dilutions,and confirmed by≥20 replicates per level.In a 158-sample validation set(38 mutation-positive;120 negative),qPCR agreed perfectly with Sanger sequencing(Cohen’s kappa coefficient(κ)=1.0).Probit analysis yielded locus-specific limit of detection(LoD)values ranging from 0.035 to 0.200 ng/μL;at 0.200 ng/μL,the detection rate was over 95%.Repeatability and intermediate precision were high(CT coefficient of variation(CV)0.34%-1.21%).No cross-reactivity was observed against non-target TGFBI variants or other ophthalmic genes,and interference from blood,oral florainse,or toothpaste produced small,bounded shifts(approximately−7.8%to+2.8%).Calibration with serial dilutions demonstrated linear CT-log(copy)relationships suitable for routine quality control.Prospective screening of 10055 refractive surgery candidates identified six TGFBI carriers(0.06%)harboring R124H(including one homozygote),R124L,R124C,or R555W mutation,all confirmed by Sanger sequencing.This study established a clinically applicable,statistically optimized multiplex qPCR platform that integrated ROC-derived cut-offs and Probit-defined LoD with rigorous evaluations of precision,specificity,and robustness,enabling large-scale population implementation.Positive screening results guide clinical decision-making through a standardized post-screening workflow,and the targeted hotspot screening strategy serves as a cost-effective first-tier high-throughput approach for preoperative risk assessment.The framework provides a transparent,reproducible path to standardize preoperative TGFBI screening and reduce iatrogenic risk in refractive surgery candidates. 展开更多
关键词 Multiplex real-time quantitative polymerase chain reaction(qPCR) Transforming growth factor-β-induced(TGFBI)mutation Preoperative genetic screening Probit regression analysis Refractive surgery
暂未订购 下载PDF
A novel compound heterozygous mutation in ADAMTS17 identified in a Chinese family with Weill-Marchesani syndrome 认领 引用
19
作者 Hao-Yue Wu Si-Wei Liu +3 位作者 Zhao Liu Cheng Pei Chang-Rui Wu Shan Gao 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2026年第2期239-246,共8页
AIM:To investigate the genetic basis of Weill-Marchesani syndrome(WMS)in a Chinese family and clarify the pathogenic mechanism of novel ADAMTS17 mutations.METHODS:Comprehensive clinical assessments and genetic analyse... AIM:To investigate the genetic basis of Weill-Marchesani syndrome(WMS)in a Chinese family and clarify the pathogenic mechanism of novel ADAMTS17 mutations.METHODS:Comprehensive clinical assessments and genetic analyses were performed on a Chinese family with two affected siblings.Whole-exome sequencing(WES)was conducted for the proband and other family members.Bioinformatics tools were used to evaluate the conservation,predicted pathogenicity,and structural effects of the identified ADAMTS17 variants.In addition,protein structure modeling was applied to assess the functional impacts of the mutations.RESULTS:The proband(a 32-year-old male)and his elder sister(42y)presented typical clinical features of WMS,including short stature,brachydactyly,high myopia,ectopia lentis,and secondary glaucoma.WES identified a novel compound heterozygous mutation in ADAMTS17:a splicing mutation(c.451-2A>G)inherited from the father and a missense mutation(c.1043G>A;p.C348Y)inherited from the mother.The splicing mutation disrupted normal mRNA splicing and processing,leading to premature translation termination.The missense mutation,which is located in the metalloprotease catalytic domain,was predicted to abolish a critical disulfide bond,thereby impairing protein stability.Both mutations exhibited high evolutionary conservation and were predicted to be pathogenic by multiple bioinformatics algorithms.CONCLUSION:A novel compound heterozygous mutation in ADAMTS17 is identified in this WMS-affected Chinese family,and its pathogenicity is verified via bioinformatics analysis and protein structural modeling.These findings are expected to facilitate the genetic diagnosis of WMS and deepen the understanding of its molecular pathogenesis. 展开更多
关键词 Weill-Marchesani syndrome ADAMTS17 compound heterozygous mutation molecular genetics bioinformatics
暂未订购 下载PDF
Early-onset hepatic fibrosis linking to a novel PYROXD2 mutation:A case report 认领 引用
20
作者 Zhen-Yao Jiang Rong-Qiang Liu +5 位作者 Meng-Juan Tang Han-Dong Fan Wen-Jun Yang Ling Gong Xiao-Xiao Mi Jun-Ping Shi 《World Journal of Hepatology》 2026年第5期303-312,共10页
BACKGROUND Early-onset liver fibrosis is predominantly driven by inherited genetic mutations that disrupt critical metabolic or structural pathways in the liver.Pyridine nucleotide-disulfide oxidoreductase domain 2(PY... BACKGROUND Early-onset liver fibrosis is predominantly driven by inherited genetic mutations that disrupt critical metabolic or structural pathways in the liver.Pyridine nucleotide-disulfide oxidoreductase domain 2(PYROXD2)(formerly named YueF)is a mitochondrial inner membrane/matrix-localized protein,regulating mitochondrial respiratory chain function.While emerging evidence highlights the role of PYROXD2 in mitochondrial redox homeostasis and respiratory chain integrity,its pathological contribution to early-onset liver fibrosis remains poorly characterized,particularly in the context of monogenic metabolic disorders and oxidative stress-mediated hepatocyte injury.CASE SUMMARY This report represents the first description of early-onset liver fibrosis in a patient harboring a heterozygous variant in the PYROXD2 gene.The patient presented with severe obesity,recurrent abnormalities in liver enzyme levels,and hyperuricemia,and demonstrated a suboptimal or absent response to hepatoprotective therapies.Wholeexome sequencing followed by Sanger validation identified a frameshift variant in the PYROXD2 gene(NM_032709.3,c.1082dupT,p.Phe361 Leu fs*50)in the affected patient.The variant was absent from population databases(gnomAD,1000 Genomes)and had not been previously reported in the literature.Computational pathogenicity predictions consistently classified it as pathogenic.Protein modeling using SWISS-MODEL indicated that the variant induces deleterious conformational alterations.CONCLUSION Collectively,the present case highlights PYROXD2 as a novel candidate gene,contributing to early-onset liver fibrogenesis.The identification of this variant in the PYROXD2 gene in the patient demonstrates a previously unrecognized molecular pathway in juvenile hepatic fibrosis,with potential implications for personalized diagnosis and treatment. 展开更多
关键词 Early-onset liver fibrosis PYROXD2 Obesity Hyperuricemia Frameshift mutation Mitochondrial dysfunction Metabolic disorder Case report
暂未订购 下载PDF
已选0条
引用分析
参考文献
引证文献
 统计分析
检索结果
已选文献
上一页 1 2 … 146 下一页 到第 页
在线咨询 使用帮助 返回顶部 意见反馈