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A novel POU domain class 3 transcription factor 4 mutation causes X-linked non-syndromic hearing loss in a Chinese family

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Chinese Medical Journal 2019年第18期132卷 2251-2253页

作者： Hong-Min Wu Hui-Qun Jie Hui Wang Ya-Qin Wu Zheng-Nong Chen Ya-Zhi Xing Ji-Ping Wang Hai-Bo Shi Shan-Kai Yin Department of Otolaryngology Sixth People’s Hospital Shanghai Jiao Tong University Otolaryngology Institute of Shanghai Jiao Tong University Shanghai 200233 China Shanghai Key Laboratory of Sleep Disordered Breathing Shanghai 200233 China

To the Editor: POU domain class 3 transcription factor 4 or BRN-4 (POU3F4) is a causative gene of non-syndromic X-linked hearing loss (HL), which is characterized by inner ear anomalies. To date, six X-linked non-syndromic HL loci (DFNX1-6) have been mapped to chromosome X and five of these genes have been identified: phosphoribosyl pyrophosphate synthetase 1 (PRPS1)(DFNX1, OMIM: 304500), POU3F4 (DFNX2, OMIM: 304400),[1] small muscle protein, X-linked (SMPX)(DFNX4, OMIM: 300066), apoptosis-inducing factor, mitochondria-associated, 1 (AIFM1)(DFNX5, OMIM: 300614), and collagen, type IV alpha-6 (COL4A6)(DFNX6, OMIM;300914). POU3F4 mutation accounts for nearly 50% of all cases of DFNX.

关键词： hearing loss phosphoribosyl pyrophosphate muscle protein

Effects of melatonin on primary insomnia in middle-aged patients: a randomized placebo controlled study

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Effects of melatonin on primary insomnia in middle-aged pati...

中国睡眠研究会第十一届全国学术年会

作者： Yingjun Qian Xinyi Li Huajun Xu Lili Meng Jianyin Zou Huaming Zhu Suru Liu Hongliang Yi Jian Guan Shankai Yin shanghai Jiao Tong University Affiliated Sixth People’s Hospital Shanghai Key Laboratory of Sleep Disordered Breathing Disorder

Objective To investigate the effects of melatonin on primary insomnia in middle-aged patients. Design: Single center parallel randomized controlled trial. Methods This trial was conducted in a teaching hospital. 111 primary insomnia patients aged 45-60 years recruited from the near neighborhood of the hospital were randomly assigned in the melatonin and placebo group by the random number method in the computer system. The intervention included four-weeks consume of melatonin or placebo with the same appearance and taste daily 1 h before bedtime. Objective sleep parameters（including sleep latency, rapid eye movement sleep latency, wake duration during sleep, wake times during sleep, total sleep time, sleep efficiency, early wake and percentage of N1, N2, N3, rapid eye movement sleep stages） were tested before and right after the 4-weeks treatment. Standard overnight polysomnography were applied with electrodes including electroencephalograms;electrooculogram;bipolar submental electromyographic, thoracic, and abdominal movements;oronasal airflow（employing a thermocouple and a pressure cannula）;and finger pulse oximetry. Subjective sleep performance was measured by the Pittsburgh sleep Quality Index, Insomnia Severity Index and Epworth sleepiness Scale. The participants and those assessing the outcomes were blinded to the group assignment. Results 56 patients were randomized to the melatonin group and 55 to the placebo group. By the end of the treatment, 51 patients in the melatonin and 46 in the placebo groups were analyzed. A greater increase in total sleep time was achieved in the melatonin vs placebo group（11 min vs-17 min;difference, 29.12 min [95% confidence interval, 3.15 to 55.09];P = 0.028）. A greater decrease in early morning wake time was shown in melatonin than placebo group（-6 min vs 32 min;difference,-38.63 min [95% confidence interval,-60.28 to-16.98];P = 0.001）. Rapid eye movement percent increase was greater in the melatonin group than in the placebo group（4.4% vs 0.4%;difference, 4.04% [95% confide

关键词： primary insomnia melatonin randomized polysomnography Pittsburgh sleep Quality Index

Removal of biofilm is essential for long-term ventilation tuberetention

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World Journal of Clinical Cases 2020年第9期8卷 1592-1599页

作者： Qiang Ma Hui Wang Zheng-Nong Chen Ya-Qin Wu Dong-Zhen Yu Peng-Jun Wang Hai-Bo Shi Kai-Ming Su Department of Otorhinolaryngology–Head&Neck Surgery the Sixth People’s Hospital Affiliated to Shanghai Jiaotong UniversityShanghai 200233China Shanghai Key Laboratory of Sleep Disordered Breathing Shanghai 200233China

BACKGROUND Although long-term retention of a ventilation tube is required in many ear diseases,spontaneous removal of conventional ventilation tube is observed in patients within 3 to 12 mo.To address this issue,we aimed to determine a new method for long-term retention of the ventilation tube.AIM To explore the value of removing the biofilm for long-term retention of tympanostomy ventilation tubes.METHODS A case-control study design was used to evaluate the safety and effectiveness of long-term tube retention by directly removing the biofilm(via surgical exfoliation)in patients who underwent myringotomy with ventilation tube placement.The patients were randomly divided into two groups:Control group and treatment group.Patients in the treatment group underwent regular biofilm exfoliation surgery in the clinic,whereas those in the control group did not have their biofilm removed.Only conventional ventilation tubes were placed in this study.Outcome measures were tube position and patency.Tube retention time and any complications were documented.RESULTS Eight patients with biofilm removal and eight patients without biofilm removal as a control group were enrolled in the study.The tympanostomy tube retention time was significantly longer in the treatment group(43.5±26.4 mo)than in the control group(9.5±6.9 mo)(P=0.003).More tympanostomy tubes were found to be patent and in correct position in the treatment group during the follow-up intervals than in the control group(P=0.01).CONCLUSION Despite the use of short-term ventilation tubes,direct biofilm removal can be a well-tolerated and effective treatment for long-term tube retention of tympanostomy ventilation tubes in patients who underwent myringotomy.

关键词： Tympanostomy tubes Biofilm Complication management Long-term retention Ménière disease Refractory otitis media with effusion

A zebrafish model for hearing loss and regeneration induced by blast wave

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Journal of Bio-X Research 2019年第2期2卷 87-97页

作者： Jiping Wang Zheng Yan Yazhi Xing Ke Lai Jian Wang Dongzhen Yu Haibo Shi Shankai Yin Department of Otolaryngology Affiliated Sixth People’s Hospital of Shanghai Jiao Tong University Shanghai Key Laboratory of Sleep Disordered Breathing National key laboratory of Science and Technology on Underwater Acoustic Antagonizing shanghai Marine Electronic Equipment Research Institute ShanghaiChina School of Human Communication Disorder Dalhousie UniversityHalifaxNova ScotiaCanada

Zebrafish have the potential to regrow injured organs and tissues,but their use as a model for hearing regeneration following blast injury has never been reported.In this study,zebrafish were exposed to a blast wave produced by an underwater blast wave generator.The first peak sound pressures produced by this generator were up to 224dB and 160kPa,measured at 25cm away from the machine.Zebrafish hearing sensitivity was examined by analyzing auditory evoked potentials from 1 to 35 days post blast wave exposure.Cell death and cell proliferation in inner ear organs,including the saccule,lagena,and utricle,were investigated using a terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay,and cell proliferation assay using 5-ethynyl-20-deoxyuridine,respectively.Significant differences in auditory evoked potential thresholds were observed between exposed and control groups,demonstrating both blast wave-induced hearing loss and recovery of hearing sensitivity.An apoptosis assay revealed significantly increased numbers of terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labelingpositive cells in the inner ear sensory epithelia of exposed groups compared with the control group.However,numbers of 5-ethynyl-20-deoxyuridine-positive cells in the inner ear of exposed groups recovered to a normal level within 10 post blast wave exposure.Furthermore,blast wave exposure caused brain injury with increased cell apoptosis and decreased neurogenesis.Compared with drug or noise-induced zebrafish models,our blast wave-induced model elicited more serious hearing loss phenotypes,which required more time to return to a normal level.Overall,this zebrafish model can provide a reliable animal model for both hearing loss and regeneration research.The study was approved by the shanghai 6th Hospital Animal Care and Use Committee,China(approval No.2017-0196)on February 28,2017.

关键词： blast wave zebrafish hearing loss brain injury auditory evoked potential hair cell apoptosis regeneration

Epidemiology of sleep disturbances during pregnancy and OSA in the first pregnant trimester:a multicenter cross-sectional study

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Epidemiology of sleep disturbances during pregnancy and OSA ...

中国睡眠研究会第十二届全国学术年会

作者：张楚珺粟义佳许华俊刘玉璞易红良关建殷善开 Department of Otolaryngology-Head and Neck Surgery & Center of sleep Medicine Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai Key Laboratory of Sleep Disordered Breathing Otolaryngology Institute of shanghai Jiao Tong University

＜正＞Objective:We aimed to investigate the prevalence of sleep disturbances and OSA in the pregnant population and how it varied between subgroups.Methods:Type III portable sleep monitor and integrated online sleep questionnaires were used to diagnose various sleep disturbances.Results:4765 valid questionnaires and 152 qualified sleep monitoring records were analyzed.

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Association between Upper-airway Surgery and Ameliorative Risk Markers of Endothelial Function in Obstructive sleep Apnea

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Association between Upper-airway Surgery and Ameliorative Ri...

中国睡眠研究会第十一届全国学术年会

作者： Fan Wang Yuenan Liu Huajun Xu Yingjun Qian Jianyin Zou Hongliang Yi Jian Guan Shankai Yin Department of Otolaryngology Head and Neck Surgery & Center of sleep Medicine Shanghai Jiao Tong University Affiliated Sixth People’s Hospital Shanghai Key Laboratory of Sleep Disordered Breathing Clinical Research Center Shanghai Jiao Tong University School of Medicine

Objectives To evaluate the effects of upper-airway surgery aimed at solving oropharyngeal and retrolingual plane obstruction on improvement of endothelial function-related markers in patients with obstructive sleep apnea(OSA). Methods Subjects with moderate to severe OSA who underwent upper-airway surgery between 2004 and 2013, with a follow-up duration of at least 6 months, were included. Pre-and postoperative polysomnographic variables, Clinical and biochemical measurement and endothelial function-related markers(inflammatory adhesion molecules, endothelial cell propermeability markers, hypercoagulability-related markers and endothelium-stabilizing markers) were compared. Subgroup and correlation analyses were conducted to find possible indicators for better endothelial function-related markers after upper-airway surgery. Results In total, 44 patients with OSA were included. The mean follow-up duration was 1.72 ± 0.92 years. The proportion of surgical success was 40%. Postoperative sleep parameters, including AHI, ODI, CT90, MAI, ESS, mean SpO, and lowest SpO, all improved(p < 0.01). Neither BMI nor WC of the patients changed significantly after surgery. Reductions were evident in a number of cardiovascular-related biomarkers, including fasting glucose(p < 0.05), HOMA-IR(p < 0.05), fasting TC(p < 0.001), fasting LDL-C(p < 0.05), and fasting Apo B(p < 0.001). SBP, DBP, TG, HDL-C, and Apo A did not change significantly after surgery. Serum VEGFA [-20.29(CI:-35.27,-5.31), p<0.05], Ang2 [-0.06(CI:-0.16, 0.03), p<0.05], E-selectin [-7.21(CI:-11.01,-3.41), p<0.001], VWF [-58.83(CI:-103.93,-13.73), p<0.05], VWFCP [-33.52(CI:-66.34,-0.70), p < 0.05], and TM [-0.06(CI:-0.09,-0.03), p < 0.05] were significantly lower after upper-airway surgery. However, other risk markers of endothelial function, such as Ang1, ICAM1, VEGFR1, and VCAM, did not change significantly. Correlations between improved endothelial function-related markers and ameliorated oxyhemoglobin saturation and glucolipid metabolism were established. VEGFA w

关键词： endothelial function obstructive sleep apnea upper-airway surgery

Structural Comparison and Drug Screening of Spike Proteins of Ten SARS-CoV-2 Variants

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Research 2022年第2期2022卷 5-24页

作者： Qiangzhen Yang Xuemin Jian Ali Alamdar Shah Syed Aamir Fahira Chenxiang Zheng zijia Zhu Ke Wang Jinmai Zhang Yangin Wen Zhiqiang Li Dun Pan Tingting Lu Zhuo Wang Yongyong Shi Bio-X Institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders(Ministryof Education)Shanghai jiao Tong University1954 Huashan RoadShanghai 200030China Biomedical Sciences Insttuteof Qingdao University(Qingdao Branch of SJTU Bio-X Institutes) Qingdao University Qingdao 266003China shanghai key laboratory of Psychotic Disorders Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghai 200030China Shanghai Key Laboratory of Sleep Disordered Breathing Shanghai liao Tong University Afliated Sixth People's Hospital.ShanghaiChina The First Afiliated Hospital of Zhengzhou Universily Zhengzhou 450052China Deparment of Psychiary First Teaching Hospital of Xinjiang Medical UniversitUrumqi 830046China

SARS-CoV-2(severe acute respiratory syndrome coronavirus 2)has evolved many variants with stronger infectivity and immune evasion than the original strain,including Alpha,Beta,Gamma,Delta,Epsilon,Kappa,lota,Lambda,and 21H strains.Amino acid mutations are enriched in the spike protein of SARS CoV-2.which plays a crucial role in cell infetion.However,the impact of these mutations on protein structure and function is unclear.Understanding the pathophysiology and pandemic feaures of these SARS-CoV-2 variants requires knowledge of the spike protein structures.Here,we obtained the spike protein structures of 10 main globally endemic SARS CoV-2 strains using AlphaFold2.The clustering analysis based on structural similarity revealed the unique features of the mainly pandemic SARS CoV-2 Delta variants.indicating that structural clusters can reflect the current characteristics of the epidemic more accurately than those based on the protein sequence.The analysis of the binding afinities of ACE2-RBD,antibody-NTD,and antibody-RBD complexes in the different variants revealed that the recognition of antibodies against SI NTD and RBD was decreased in the variants,especally the Delta variant compared with the original strain,which may induce the immune evasion of SARS-CoV-2 variants.Furthermore,by virtual screening the ZINC database against a high-accuracy predicted structure of Delta spike protein and experimental validation,we identified multiple compounds that target S1 NTD and RBD,which might contribute towards the development of clinical anti-SARS-CoV-2 medicines.Our findings provided a basic foundation for future in vitro and in vivo investigations that might speed up the development of potential therapies for the SARS-CoV-2 va riants.

关键词： globally similarity finding

Structural Analysis of the SARS-CoV-2 Omicron Variant Proteins

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Research 2021年第2期2021卷 759-762页

作者： Qiangzhen Yang Ali Alamdar Shah Syed Aamir Fahira Yongyong Shi Bio-X Institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders(Ministry of Education)Shanghai Jiao Tong University1954 Huashan RoadShanghai 200030China Biomedical Sciences Institute of Qingdao University(Qingdao Branch of SJTU Bio-X Institutes) Qingdao UniversityQingdao 266003China shanghai key laboratory of Psychotic Disorders Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghai 200030China Shanghai Key Laboratory of Sleep Disordered Breathing Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghaiChina The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052China Department of Psychiatry First Teaching Hospital of Xinjiang Medical UniversityUrumqi830046China

The spread of the latest SARS-CoV-2 variant Omicron is particularly concerning because of the large number of mutations present in its genome and lack of knowledge about how these mutations would affect the current SARS-CoV-2 vaccines and treatments.Here,by performing phylogenetic analysis using the Omicron spike(S)protein sequence,we found that the Omicron S protein presented the longest evolutionary distance in relation to the other SARS-CoV-2 variants.We predicted the structures of S,M,and N proteins of the Omicron variant using AlphaFold2 and investigated how the mutations have affected the S protein and its parts,S1 NTD and RBD,in detail.We found many amino acids on RBD were mutated,which may influence the interactions between the RBD and ACE2,while also showing the S309 antibody could still be capable of neutralizing Omicron RBD.The Omicron S1 NTD structures display significant differences from the original strain,which could lead to reduced recognition by antibodies resulting in potential immune escape and decreased effectiveness of the existing vaccines.However,this study of the Omicron variant was mainly limited to structural predictions,and these findings should be explored and verified by subsequent experiments.This study provided basic data of the Omicron protein structures that lay the groundwork for future studies related to the SARS-CoV-2 Omicron variant.

关键词： concerning subsequent neutral

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LENG8 regulation of mRNA processing controls mitochondria activity

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LENG8 regulation of mRNA processing controls mitochondria ac...

中国生物化学与分子生物学会2020全国学术在线会议

作者： Yongxu Zhao Xiaoting Wang Yuenan Liu Niannian Li Shengming Wang Hongliang Yi Nan Zhang Qiurong Ding Feng Liu Department of Otolaryngology-Head and Neck Surgery Otolaryngology Institute of Shanghai JiaoTong UniversityShanghai JiaoTong University Affiliated Sixth People's Hospital CAS key laboratory of Nutrition Metabolism and Food SafetyShanghai Institute of Nutrition and HealthShanghai Institutes for Biological SciencesUniversity of Chinese Academy of SciencesChinese Academy of Sciences Shanghai Key Laboratory of Sleep Disordered Breathing Department of Oncology Jinan Central HospitalCheeloo College of MedicineShandong University

mRNA processing is essential for the maintenance of cellular and tissue homeostasis.However,how this process is precisely regulated in mammalian cells remains largely unknown.Here we demonstrate that LENG8 is the mammalian orthologous counterpart of yeast mRNA processing factor Thp3.We show that LENG8 binds mRNA,associates with components of mRNA processing machinery TREX complex and contributes to mRNA export.Loss of LENG8 leads to aberrant accumulation of poly(A) RNA in nucleus in both Hela cells and murine fibroblasts.LENG8 precipitates shows high enrichment of mRNAs and lncRNAs,about half of which are also bound by THO/TREX component THOC1.However when compared to THOC1,LENG8 preferentially bound mRNA encoding mitochondria proteins and depletion of LENG8 dramatically destroys mitochondria structures and reduces mitochondrial respiratory activity.Our work therefore reveals an evolutionarily conserved mRNA processing factor that controls mitochondria activity.

关键词： RNA metabolism mRNA export mRNP biogenesis mitochondria