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Total glucosides of paeony alleviates cGAS-STING-mediated diseases by blocking the STING-IRF3 interaction

Chinese Journal of Natural Medicines 2024年第5期22卷 402-415页

作者： XIU Ye WANG Sihao ZHANG Ping LI Chengwei WU Zhixin WEN Jincai XU Yingjie LV Guiji ZHAO Xiaomei DONG Xu CHEN Yichong LI Junjie WANG Yan ZOU Liang XIAO Xiaohe BAI Zhaofang School of Pharmacy Fujian University of Traditional Chinese MedicineFuzhou 350122China Department of Hepatology The Fifth Medical Center of PLA General HospitalBeijing 100039China China military Institute of Chinese Materia Fifth Medical Center of Chinese PLA General HospitalBeijing 100039China Department of Pharmacy Medical Supplies Center of PLA General HospitalBeijing 100039China School of Food and Biological Engineering Chengdu UniversityChengdu 610106China National Key Laboratory of Kidney Diseases Chinese PLA General HospitalBeijing 100039China

In the realm of autoimmune and inflammatory diseases,the cyclic GMP-AMP synthase(cGAS)stimulator of interferon genes(STING)signaling pathway has been thoroughly investigated and *** this,the clinical approval of drugs targeting the cGAS-STING pathway has been *** Total glucosides of paeony(TGP)is highly anti-inflammatory and is commonly used in the treatment of rheumatoid arthritis(RA),emerged as a subject of our *** found that the TGP markedly reduced the activation of the cGAS-STING signaling pathway,triggered by various cGAS-STING agonists,in mouse bone marrow-derived macrophages(BMDMs)and Tohoku hospital Pediatrics-1(THP-1)*** inhibition was noted alongside the suppression of interferon regulatory factor 3(IRF3)phosphorylation and the expression of interferon-beta(IFN-β),C-X-C motif chemokine ligand 10(CXCL10),and inflammatory mediators such as tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6).The mechanism of action appeared to involve the TGP’s attenuation of the STING-IRF3 interaction,without affecting STING oligomerization,thereby inhibiting the activation of downstream signaling *** vivo,the TGP hindered the initiation of the cGAS-STING pathway by the STING agonist dimethylxanthenone-4-acetic acid(DMXAA)and exhibited promising therapeutic effects in a model of acute liver injury induced by lipopolysaccharide(LPS)and D-galactosamine(D-GalN).Our findings underscore the potential of the TGP as an effective inhibitor of the cGAS-STING pathway,offering a new treatment avenue for inflammatory and autoimmune diseases mediated by this pathway.

关键词： Total glucosides of gaeony cGAS-STING pathway Inflammation LPS/D-GalN STING inhibitor

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Surface demineralized freeze-dried bone allograft followed by reimplantation in a failed mandibular dental implant

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Regenerative Biomaterials 2024年第1期3卷 82-93页

作者： Jing Zhang Jie Wang Jiayi You Xuan Qin Huimin Chen Xiantong Hu Yantao Zhao Yang Xia Jiangsu Key Laboratory of Oral Diseases Nanjing Medical UniversityNanjingJiangsu 210029PR China Jiangsu Province Engineering Research Center of Stomatological Translational Medicine Nanjing Medical UniversityNanjingJiangsu 210029PR China Department of Restorative Dental Sciences Faculty of DentistryThe University of Hong KongHong Kong SARPR China Senior Department of Orthopedics The Fourth Medical Center of PLA General HospitalBeijing100048PR China Beijing Engineering Research Center of Orthopedics Implants Beijing 100048PR China State Key Laboratory of military Stomatology Xi'an 710032PR China

The removal of a failed implant with high torque causes significant damage to the surrounding tissue,compromising bone regeneration and subsequent osseointegration in the defect ***,we report a case of carrier screw fracture followed by immediate implant removal,bone grafting and delayed reimplantation.A dental implant with a fractured central carrier screw was removed using the bur-forceps *** resulting three-wall bone defect was filled with granular surface demineralized freeze-dried bone allograft(SD-FDBA).Cone-beam computerized tomography was performed at 1week,6months and 15months postoperatively and standardized for quantitative *** alveolar bone width and height at 15months post-surgery were about 91%of the original values,with a slightly lower bone density,calculated using the gray value *** graft site was reopened and was found to be completely healed with dense and vascularized bone along with some residual bone *** followed by restoration was performed 8months *** quality of regenerated bone following SD-FDBA grafting was adequate for osseointegration and longterm implant *** excellent osteogenic properties of SD-FDBA are attributed to its human origin,cortical bone-like structure,partly demineralized surfaces and bone morphogenetic protein-2-containing *** investigation with more cases and longer follow-up was required to confirm the final clinical effect.

关键词： dental implant implant failure allogeneic bone bone regeneration reimplantation

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Advances in the treatment of IgA nephropathy with biological agents

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Chronic Diseases and Translational Medicine 2024年第1期10卷 1-11页

作者： Yongze Zhuang Hailing Lu Junxia Li Department of Nephrology 900 Hospital of the Joint Logistics TeamPLAFuzhou General Clinical Medical CollegeFujian Medical UniversityFuzhouFujianChina

Immunoglobulin A nephropathy(IgAN)is the most common primary glomerular disease,and the“four-hit”theory represents its currently accepted pathogenic *** immunity triggered by infections in the respiratory tract,intestines,or other areas leads to antigen presentation,T cell stimulation,B cell maturation,and the production of IgA-producing plasma *** proteins B-lymphocyte stimulator(BLyS)and a proliferation-inducing ligand(APRIL)are involved in this process,and alternative complement and lectin pathway activation are also part of the pathogenic *** Disease Improving Global Outcomes guidelines indicate that a specific effective treatment for IgAN is lacking,with renin-angiotensin-aldosterone system inhibitors being the primary *** research shows that biological agents can significantly reduce proteinuria,stabilize the estimated glomerular filtration rate,and reverse some pathological changes,such as endocapillary proliferation and crescent *** are four main categories of biological agents used to treat IgA nephropathy,specifically anti-CD20 monoclonal antibodies,anti-BLyS or APRIL monoclonal antibodies,monoclonal antibodies targeting both BLyS and APRIL(telitacicept and atacicept),and monoclonal antibodies inhibiting complement system activation(narsoplimab and eculizumab).However,further research on the dosages,treatment duration,long-term efficacy,and safety of these biological agents is required.

关键词： anti-CD20 monoclonal antibodies APRIL biological agents BLyS complement IgAnephropathy

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The Relationship between Viral Replication and the Severity of Hepatic Necroinflammatory Damage Changed before HBeAg Loss in Patients with Chronic Hepatitis B Virus Infection

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Journal of Clinical and Translational Hepatology 2024年第4期12卷 381-388页

作者： Leijie Wang Jian Wang Kunyu Zhao Lina Jiang Xinxin Zhang Jingming Zhao Jie Li Fengmin Lu Department of Microbiology and Immunology College of Basic Medical SciencesZhengzhou UniversityZhengzhouHenanChina Department of Microbiology&Infectious Disease Center School of Basic Medical SciencesPeking UniversityBeijingChina Department of Infectious Diseases Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsuChina Department of Pathology and Hepatology The Fifth Medical Center of PLA General HospitalBeijingChina Department of Infectious Diseases Rui Jin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

Background and Aims:Disease progression of chronic hepatitis B virus(HBV)infection is driven by the interactions between viral replication and the host immune response against the *** study aimed to clarify the relationship between HBV replication and hepatic inflammation during disease ***:Two cross-sectional,one validation cohort,and meta-analyses were used to explore the relationship between HBV replication and liver *** analysis,multiple linear regression,and logistic regression were used to explore the relationship between ***:In the cross-sectional cohorts A and B including 1,350 chronic hepatitis B patients,Spearman analysis revealed a negative relationship between HBV replication(such as HBV DNA)and liver inflammation(such as ALT)in HBeAg-positive patients with higher HBV DNA>2×10^(6) IU/mL(rho=0.278 and 0.260)and HBeAg-negative patients(rho=0.450 and 0.363).After adjustment for sex,age,and anti-HBe,results from logistic regression and multiple linear regression showed the opposite relationship still existed in HBeAg-positive patients with different DNA levels;the opposite relationship in HBeAg-positive patients with different DNA levels was validated in a third cohort;the opposite relationship in patients with different HBeAg status was partially confirmed by meta-analysis(overall R:-0.004 vs 0.481).Conclusions:These results suggested a negative relationship between viral replication and liver inflammation in HBeAgpositive patients with high HBV DNA,which changed to a positive relationship for those HBeAg-positive patients with DNA less than 2×10^(6) IU/mL and HBeAg-negative patients.

关键词： Chronic hepatitis B HBeAg HBV DNA ALT.

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Nucleotide excision repair gene polymorphisms and hepatoblastoma susceptibility in Eastern Chinese children:A five-center case-control study

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Chinese Journal of Cancer Research 2024年第3期36卷 298-305页

作者： Huimin Yin Xianqiang Wang Shouhua Zhang Shaohua He Wenli Zhang Hongting Lu Yizhen Wang Jing He Chunlei Zhou Department of Pediatric Surgery Guangzhou Institute of PediatricsGuangdong Provincial Key Laboratory of Research in Structural Birth Defect DiseaseGuangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangzhou 510623China Department of Pediatric Surgery Senior Department of Pediatricsthe Seventh Center of Chinese People’s Liberation Army(PLA)General HospitalBeijing 100000China Department of general Surgery Jiangxi Provincial Children’s HospitalNanchang 330006China Department of Pediatric Surgery Shengli Clinical Medical College of Fujian Medical UniversityFuzhou 350001China Department of Pediatric Surgery Qingdao Women and Children’s HospitalQingdao 266000China Department of Pathology Anhui Provincial Children’s HospitalHefei 230051China Department of Pathology Children’s Hospital of Nanjing Medical UniversityNanjing 210008China

Objective:Nucleotide excision repair(NER)plays a vital role in maintaining genome stability,and the effect of NER gene polymorphisms on hepatoblastoma susceptibility is still under *** study aimed to evaluate the relationship between NER gene polymorphisms and the risk of hepatoblastoma in Eastern Chinese Han ***:In this five-center case-control study,we enrolled 966 subjects from East China(193 hepatoblastoma patients and 773 healthy controls).The TaqMan method was used to genotype 19 single nucleotide polymorphisms(SNPs)in NER pathway genes,including ERCC1,XPA,XPC,XPD,XPF,and ***,multivariate logistic regression analysis was performed,and odds ratios(ORs)and 95%confidence intervals(95%CIs)were utilized to assess the strength of ***:Three SNPs were related to hepatoblastoma *** rs2229090 and XPD rs3810366 significantly contributed to hepatoblastoma risk according to the dominant model(adjusted OR=1.49,95%CI=1.07−2.08,P=0.019;adjusted OR=1.66,95%CI=1.12−2.45,P=0.012,respectively).However,XPD rs238406 conferred a significantly decreased risk of hepatoblastoma under the dominant model(adjusted OR=0.68,95%CI=0.49−0.95;P=0.024).Stratified analysis demonstrated that these significant associations were more prominent in certain ***,there was evidence of functional implications of these significant SNPs suggested by online expression quantitative trait loci(eQTLs)and splicing quantitative trait loci(sQTLs)***:In summary,NER pathway gene polymorphisms(XPC rs2229090,XPD rs3810366,and XPD rs238406)are significantly associated with hepatoblastoma risk,and further research is required to verify these findings.

关键词： Nucleotide excision repair polymorphisms hepatoblastoma susceptibility

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Changes in brain function and anatomical structure following treatment of hyperbaric oxygen for visual pathway abnormalities in 16 cases Evaluation of functional magnetic resonance imaging combined with diffusion tensor imaging

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Neural Regeneration Research 2008年第2期3卷 117-123页

作者： Ziqian Chen Ping Ni Hui Xiao Jinhua Chen Gennian Qian Youqiang Ye Shangwen Xu Jinliang Wang Xizhang Yang Department of Medical Imaging Center Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA Fuzhou 350025 Fujian Province China Deparment of Medical Engineering Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA Fuzhou Province China Department of Medical Statistics Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA Fuzhou Province China

BACKGROUND： There is a growing research focus on the combination of blood oxygenation level dependent functional magnetic resonance imaging （BOLD-fMRI） and diffusion tensor imaging （DTI） to evaluate visual cortical function and structural changes in the cerebrum, as well as morphological changes to the white matter fiber tracks, after visual pathway lesions. However, the combined application of BOLD-fMRI and DTI in treating of visual pathway abnormalities still requires further studies. OBJECTIVE： To observe and evaluate the effects of hyperbaric oxygen on visual pathway abnormalities, and to evaluate the characteristics of cerebral function and anatomic structural changes by using BOLD-fMRI combined with DTI technique. DESIGN： Case contrast observation. SETTING： fuzhou general hospital of nanjing military Area command of Chinese pla. PARTICIPANTS： Sixteen patients （9 males and 7 females, 15-77 years old） with lateral or bilateral visual disorder induced by visual pathway lesions were selected from the Department of Neurology, fuzhou general hospital of nanjing military Area command of Chinese pla from January 2006 to May 2007. These patients comprised the lesion group. Measures of interventional therapy： hyperbaric oxygen of two normal atmospheres for three courses （10 d/course） and routine internal medicine treatment. In addition, 12 healthy subjects of similar sex and age to the lesion group were regarded as the control group. The control group underwent routine ophthalmological and ocular fundus examinations; diagnostic results were normal. The experiment received confirmed consent from the local ethic committee, and all patients provided informed consent. METHODS： BOLD-fMRI and DTI manifestations in the lesion group were observed before and after hyperbaric oxygen intervention, and the results were compared with the control group. The subjects were positioned on their back, and BOLD-fMRI images were collected with the following GRE EPI sequence： TR = 2

关键词： vision functional magnetic resonance imaging diffusion tensor imaging hyperbaric oxygen therapy

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Treatment with β-sitosterol ameliorates the effects of cerebral ischemia/reperfusion injury by suppressing cholesterol overload, endoplasmic reticulum stress, and apoptosis

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Neural Regeneration Research 2024年第3期19卷 642-649页

作者： Xiuling Tang Tao Yan Saiying Wang Qingqing Liu Qi Yang Yongqiang Zhang Yujiao Li Yumei Wu Shuibing Liu Yulong Ma Le Yang Precision Pharmacy&Drug Development Center Department of PharmacyTangdu HospitalAir Force Medical UniversityXi’anShaanxi ProvinceChina Department of Clinical Pharmacy Jinling HospitalMedical School of Nanjing UniversityNanjingJiangsu ProvinceChina Department of Pharmacology School of PharmacyAir Force Medical UniversityXi’anShaanxi ProvinceChina Department of Anesthesiology The First Medical Center of Chinese PLA General HospitalBeijingChina Department of Anatomy Histology and Embryology and K.K.Leung Brain Research CentreAir Force Medical UniversityXi’anShaanxi ProvinceChina

β-Sitosterol is a type of phytosterol that occurs naturally in *** studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic *** we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced *** investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic *** addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its *** conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.

关键词： apoptosis blood-brain barrier β-sitosterol cerebral ischemia/reperfusion injury cholesterol overload cholesterol transport endoplasmic reticulum stress ischemic stroke molecular docking NPC1L1

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中国胃癌肝转移患者临床诊疗特征及预后分析:全国多中心队列研究(RECORD研究)

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Science Bulletin 2024年第3期69卷 303-307页

作者：高云鹤郗洪庆商亮唐兆庆卫勃乔治唐云王鑫鑫周静汪学非黄昌明陆俊李国新余江梁延锐季加孚李子禹薛侃梁寒柯彬臧潞何子锐谢少华黄华徐泽宽田艳涛熊建平李佶阳崔秋霞李力卢婷婷宋奇嬴刘诗贺孙益红李乐平陈凛 RECORD研究协作组 Section of Gastric Surgery Senior Department of General SurgeryThe First Medical CenterChinese PLA General HospitalBeijing 100853China Section of Abdominal Trauma Surgery Senior Department of General SurgeryThe First Medical CenterChinese PLA General HospitalBeijing 100853China Institute of general Surgery The First Medical CenterChinese PLA General HospitalBeijing 100853China Department of Gastrointestinal Surgery Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250021China Department of general Surgery Fudan University Zhongshan HospitalShanghai 200032China Department of general Surgery Fujian Medical University Union HospitalFuzhou 350001China Department of general Surgery Nanfang Hospital Affiliated to Southern Medical UniversityGuangzhou 510515China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Gastrointestinal Cancer CenterPeking University Cancer Hospital&InstituteBeijing 100142China Department of Gastric Cancer Surgery Tianjin Medical University Cancer Institute and HospitalTianjin 300060China Department of general Surgery Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Institute of Population Medicine and School of Public Health Fujian Medical UniversityFuzhou 350122China Department of Gastric Surgery Fudan University Shanghai Cancer CenterShanghai 200032China Department of general Surgery Jiangsu Province HospitalNanjing Medical UniversityNanjing 210029China Department of Pancreatic and Gastric Surgery National Cancer CenterNational Clinical Research Center for CancerCancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100029China

Despite surgical improvements and pharmacological advances,management of late-stage gastric cancer patients,especially those with hepatic metastasis remains challenging[1–3].Although nationwide registry data from SEER(Surveillance,Epidemiology,and End Results)[4]and the Nordic database[5]in Western countries have provided epidemiological information for patients with gastric cancer liver metastasis(GCLM),little is known about the detailed clinical characteristics.

关键词：胃癌肝转移 metastasis cancer

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Prevalence,patterns,risk factors and outcomes of peritoneal metastases after laparoscopic hepatectomy for hepatocellular carcinoma:a multicenter study from China

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Hepatobiliary Surgery and Nutrition 2024年第1期13卷 3-15,I0001-I0004页

作者： Yuan-Xiang Lu Jian-Ping Zhao Guan-Dou Yuan Ming-Gen Hu Chuan-Dong Sun Kun-Lun Chen Yao Chen Yong-Yi Zeng Zhi-Ying Yang Wan-Guang Zhang Hepatic Surgery Center Tongji Hospital of Tongji Medical College of Huazhong University of Science and TechnologyWuhanChina Department of Hepatobiliary Surgery The First Affiliated Hospital of Guangxi Medical UniversityNanningChina Faculty of Hepato-Pancreato-Biliary Surgery Chinese PLA General HospitalBeijingChina Department of Hepatobiliary and Pancreatic Surgery The Affiliated Hospital of Qingdao UniversityQingdaoChina Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina Department of Radiology Intervention The Affiliated Tumor Hospital of Zhengzhou UniversityHenan Cancer HospitalZhengzhouChina Department of Hepatobiliary Surgery Mengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouChina Department of general Surgery China-Japan Friendship HospitalBeijingChina

Background:We aim to investigate the prevalence,patterns,risk factors,and outcomes of peritoneal metastases(PM)after curative laparoscopic hepatectomy(LH)for hepatocellular carcinoma(HCC).Methods:A multicenter cohort of 2,138 HCC patients who underwent curative LH from August 2010 to December 2016 from seven hospitals in China was retrospectively *** incidence of PM following LH was evaluated and compared with that in open hepatectomy(OH)after 1:1 propensity score matching(PSM).Results:PM prevalence was 5.1%(15/295)in the early period[2010-2013],2.6%(47/1,843)in the later period[2014-2016],and 2.9%(62/2,138)in all LH patients,which was similar to 4.0%(59/1,490)in the OH *** recurrence patterns,timing,and treatment did not significantly vary between the LH and OH patients(P>0.05).Multivariate logistic regression revealed that tumor diameter>5 cm,non-anatomical resection,presence of microvascular invasion,and lesions<2 cm from major blood vessels were independent risk factors of PM after *** the 62 cases with PM,26(41.9%)had PM only,34(54.9%)had intrahepatic recurrence(IHR)and PM,and 2(3.2%)had synchronous extraperitoneal metastases(EPM).Patients with resectable PM had a 5-year overall survival(OS)of 65.0%compared to 9.0%for unresectable PM(P=0.001).Conclusions:The prevalence,patterns and independent risk factors of PM were identified for HCC patients after *** was not associated with increased incidence of PM in HCC patients for experienced *** re-excision of PM was associated with prolonged survival.

关键词： Prevalence hepatocellular carcinoma(HCC) peritoneal metastases(PM) laparoscopic hepatectomy(LH) open hepatectomy(OH)

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Identification of two novel missense WFS1 mutations,H696Y and R703H,in patients with non-syndromic low-frequency sensorineural hearing loss

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Journal of Genetics and Genomics 2011年第2期38卷 71-76页

作者： Yi Sun Jing Cheng Yanping Lu Jianzhong Li Yu Lu Zhanguo Jin Pu Dai Rongguang Wang Huijun Yuan Institute of Otolaryngology Chinese PLA General Hospital Beijing 100853 China Department of Otolaryngology Chinese PLA Wuhan General Hospital of Guangzhou Military Command Wuhan 430070 China Department of Obstetrics and Gynecology Chinese PLA General Hospital Beijing 100853 China fuzhou general hospital of nanjing military command pla Fuzhou 350025 China

Non-syndromic low-frequency sensorineural hearing loss （LFSNHL） is an unusual type of hearing loss in which frequencies ≤2000 Hz predominantly are affected. To date, different mutations in two genes, DIAPHI and WFSI, have been found to be associated with LFSNHL. Here, we report a five-generation Chinese family with postlingual and progressive LFSNHL. We mapped the disease locus to a 2.5 Mb region on chromosome 4p16 between markers SNP_A-2167174 and D4S431, overlapping with the DFNA6/14/38 locus. Sequencing of candidate gene revealed a heterozygous c.2086C〉T substitution in exon 8 of WFS1, leading to p.H696Y substitution at the C-terminus of Wolframin （WFS 1）. In addition, we performed mutational screening of WFS1 in 37 sporadic patients, 7--50 years of age, with LFSNHL. We detected a heterozygous c.2108G〉A substitution in exon 8 of WFSI, leading to p.R703H substitution in a patient. The H696 and R703 in WFS1 are highly conserved across species, including human, orangutan, rat, mouse, and frog （Xenopus）, Sequence analysis demonstrated the absence of c.2086C〉T or c.210gG〉A substitutions in the WFS1 genes among 200 unrelated control subjects of Chinese background, supporting the hypothesis that they represent causative mutations, and not rare polymorphisms. Our data provide additional molecular and clinical information for establishing a better genotype-phenotype correlation for LFSNHL.

关键词： DFNA6/14/38 WFS1 Mutation Low-frequency hearing loss

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