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Novel MIP gene mutation causes autosomal-dominant congenital cataract

International Journal of Ophthalmology(English edition) 2024年第3期17卷 454-465页

作者： Jing-Lan Ni Hua-ming Wen Xiao-Sheng huang Qian-Wen Li Jia-Min Cai bao-Jian Fan Jun Zhao The Second Clinical Medical College Jinan UniversityShenzhen 518020Guangdong ProvinceChina Department of Ophthalmology Dongguan Chang’an HospitalDongguan 523843Guangdong ProvinceChina Shenzhen Eye Hospital Affiliated to Jinan University Shenzhen Eye InstituteShenzhen 518040Guangdong ProvinceChina Department of Oral&Maxillofacial Surgery Shenzhen Stomatology Hospital Affiliated to Shenzhen UniversityShenzhen 518040Guangdong ProvinceChina Department of Neurosurgery Massachusetts General Hospital and Harvard Medical SchoolBoston 02114MassachusettsUSA Department of Ophthalmology Shenzhen People’s Hospital(the Second Clinical Medical CollegeJinan Universitythe First Affiliated HospitalSouthern University of Science and Technology)Shenzhen 518020Guangdong ProvinceChina

●AIM:To identify disease-causative mutations in families with congenital cataract.●METHODS:Two Chinese families with autosomaldominant congenital cataract(ADCC)were recruited and underwent comprehensive eye examinations.Gene panel next-generation sequencing of common pathogenic genes of congenital cataract was performed in the proband of each family.Sanger sequencing was used to valid the candidate gene mutations and sequence the other family members for co-segregation analysis.The effect of sequence changes on protein structure and function was predicted through bioinformatics analysis.Major intrinsic protein(MIP)-wildtype and MIP-G29R plasmids were constructed and microinjected into zebrafish single-cell stage embryos.Zebrafish embryonic lens phenotypes were screened using confocal microscopy.●RESULTS:A novel heterozygous mutation(c.85G>A;p.G29R)in the MIP gene was identified in the proband of one family.A known heterozygous mutation(c.97C>T;p.R33C;rs864309693)in MIP was found in the proband of another family.In-silico prediction indicated that the novel mutation might affect the MIP protein function.Zebrafish embryonic lens was uniformly transparent in both wild-type PCS2+MIP and mutant PCS2+MIP.●CONCLUSION:Two missense mutations in the MIP gene in Chinese cataract families are identified,and one of which is novel.These findings expand the genetic spectrum of MIP mutations associated with cataracts.The functional studies suggest that the novel MIP mutation might not be a gain-of-function but a loss-of-function mutation.

关键词： congenital cataract major intrinsic protein missense mutation zebrafish model

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Inflection Point Age in the Middle and Older Women—Jiangxi Province,China,2020-2022

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China CDC weekly 2024年第9期6卷 162-167页

作者： Shanlan Yang Langlang Zhang Helang huang Jiaofeng Wang Lei Wu Zhijun bao Shanghai Institute of Infectious Disease and Biosecurity Fudan UniversityShanghaiChina Department of Gerontology Huadong Hospital Affiliated to Fudan UniversityShanghai Key Laboratory of Clinical Geriatric MedicineResearch Center on Aging and MedicineFudan UniversityShanghaiChina Jiangxi Provincial Key Laboratory of Preventive Medicine School of Public HealthNanchang UniversityNanchang CityJiangxi ProvinceChina

Summary What is already known about this topic?Previous studies have predominantly examined the micro-level aspects of women aging inflection points,while macro-level research using big data on the inflection points o... 详细信息

关键词： Middle Jiangxi currently

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Kinesin 26B modulates M2 polarization of macrophage by activating cancer-associated fibroblasts to aggravate gastric cancer occurrence and metastasis

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World Journal of Gastroenterology 2024年第20期30卷 2689-2708页

作者： Lian-Meng huang ming-Jin Zhang Department of General Surgery The 901st Hospital of PLAHefei 230031Anhui ProvinceChina

BACKGROUND The regulatory effects of KIF26B on gastric cancer(GC)have been confirmed,but the specific mechanism still needs further exploration.Pan-cancer analysis shows that the KIF26B expression is highly related to immune infiltration of cancerassociated fibroblasts(CAFs),and CAFs promote macrophage M2 polarization and affect cancers’progression.AIM To investigate the regulatory functions of KIF26B on immune and metastasis of GC.METHODS We analyzed genes’mRNA levels by quantitative real-time polymerase chain reaction.Expression levels of target proteins were detected by immunohistochemistry,ELISA,and Western blotting.We injected AGS cells into nude mice for the establishment of a xenograft tumor model and observed the occurrence and metastasis of GC.The degree of inflammatory infiltration in pulmonary nodes was observed through hematoxylin-eosin staining.Transwell and wound healing assays were performed for the evaluation of cell invasion and migration ability.Tube formation assay was used for detecting angiogenesis.M2-polarized macrophages were estimated by immunofluorescence and flow cytometry.RESULTS KIF26B was significantly overexpressed in cells and tissues of GC,and the higher expression of KIF26B was related to GC metastasis and prognosis.According to in vivo experiments,KIF26B promoted tumor formation and metastasis of GC.KIF26B expression was positively associated with CAFs’degree of infiltration.Moreover,CAFs could regulate M2-type polarization of macrophages,affecting GC cells’migration,angiogenesis,invasion,and epithelial-mesenchymal transition process.CONCLUSION KIF26B regulated M2 polarization of macrophage through activating CAFs,regulating the occurrence and metastasis of GC.

关键词： metastasis invasion macrophage

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Global Zero-relaxation Limit Problem of the Electro-diffusion Model Arising in Electro-Hydrodynamics

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Acta Mathematicae Applicatae Sinica 2024年第1期40卷 241-268页

作者： ming-hua Yang Si-ming huang Jin-yi Sun Department of Mathematics Jiangxi University of Finance and EconomicsNanchang330032China School of Public Administration Guangdong University of Foreign StudiesGuangzhou510006China College of Mathematics and Statistics Northwest Normal UniversityLanzhou730070China

In this paper,we study a global zero-relaxation limit problem of the electro-diffusion model arising in electro-hydrodynamics which is the coupled Planck-Nernst-Poisson and Navier-Stokes equations.That is,the paper deals with a singular limit problem of{u^(∈)_(t)+u^(∈)·▽u^(∈)-Δu^(∈)+▽P^(∈)=Δφ^(∈)▽φ^(∈),in R^(3)×(0,∞),▽·u^(∈)=0,in R^(3)×(0,∞),n^(∈)_(t)+u^(∈)·▽n^(∈)-Δn^(∈)=-▽·(n^(∈)▽φ^(∈)),in R^(3)×(0,∞),ct+u^(∈)·▽c^(∈)-Δc^(∈)=▽·(c^(∈)▽φ^(∈)),in R^(3)×(0,∞),∈^(-1)φ^(∈)_(t)=Δφ^(∈)-n^(∈)+c^(∈),in R^(3)×(0,∞),(u^(∈),n^(∈),c^(∈),φ^(∈))|t=0=(u0,n0,c0,φ0),in R^(3) involving with a positive,large parameter^(∈).The present work show a case that(u^(∈),n^(∈),c^(∈))stabilizes to(u^(∞),n∞,c∞):=(u,n,c)uniformly with respect to the time variable as^(∈)→+∞with respect to the strong topology in a certain Fourier-Herz space.

关键词： fourier-Herz space littlewood-Paley decomposition stability limit dissipative system

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An isolated symmetrical 2T2R cell enabling high precision and high density for RRAM-based in-memory computing

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Science China(Information Sciences) 2024年第5期67卷 287-294页

作者： Yaotian LING Zongwei WANG Yuhang YANG Lin bao Shengyu bao Qishen WANG Yimao CAI Ru huang School of Integrated Circuits Beijing Advanced Innovation Center for Integrated Circuits Peking University State Key Laboratory of Information Photonics and Optical Communications Beijing University of Posts and Telecommunications

In-memory computing(IMC), leveraging emerging memories, holds significant promise in overcoming memory limitations and improving energy efficiency. However, the prevailing IMC array structure based on serially connected transistors and memory cells(1T1R/2T2R), along with the signed weight mapping scheme, can lead to asymmetrical weight sensing issues(AWS) due to electrical asymmetry within the1T1R/2T2R structure, particularly in highly scaled cells where the transistor's resistance becomes significant. In this paper, we propose and fabricate an electrically symmetric memory cell based on a physically isolated 2T2R structure for IMC. This design aims to enhance the precision and density of RRAM-based IMC arrays. The 2T2R cells are manufactured using the back-end-of-line(BEOL) process of a commercial40 nm technology platform. The feasibility of this design is verified through measured and simulated results,showcasing its capability to address the issue of AWS. Compared to conventional 2T2R cells, this design achieves a considerably smaller transistor footprint without compromising accuracy, while also improving integration density by 42.2%. These innovative memory cell advancements have the potential to further advance high-energy-efficient IMC technology.

关键词： RRAM 2T2R multi-level storage weight asymmetry in-memory computing

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Drug repurposing for cancer therapy

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1981-2013页

作者： Ying Xia ming Sun Hai huang Wei-Lin Jin Center for Clinical Laboratories The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550004PR China The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine Guiyang 550001PR China School of Clinical Laboratory Science Guizhou Medical UniversityGuiyang 550004PR China Division of Gastroenterology and Hepatology Department of Medicine andDepartment of OncologySidney Kimmel Comprehensive Cancer CenterJohns Hopkins University School of MedicineBaltimoreMD 21287USA Institute of Cancer Neuroscience Medical Frontier Innovation Research CenterThe First Hospital of Lanzhou UniversityThe First Clinical Medical College of Lanzhou UniversityLanzhou 730000PR China

Cancer,a complex and multifactorial disease,presents a significant challenge to global health.Despite significant advances in surgical,radiotherapeutic and immunological approaches,which have improved cancer treatment outcomes,drug therapy continues to serve as a key therapeutic strategy.However,the clinical efficacy of drug therapy is often constrained by drug resistance and severe toxic side effects,and thus there remains a critical need to develop novel cancer therapeutics.One promising strategy that has received widespread attention in recent years is drug repurposing:the identification of new applications for existing,clinically approved drugs.Drug repurposing possesses several inherent advantages in the context of cancer treatment since repurposed drugs are typically cost-effective,proven to be safe,and can significantly expedite the drug development process due to their already established safety profiles.In light of this,the present review offers a comprehensive overview of the various methods employed in drug repurposing,specifically focusing on the repurposing of drugs to treat cancer.We describe the antitumor properties of candidate drugs,and discuss in detail how they target both the hallmarks of cancer in tumor cells and the surrounding tumor microenvironment.In addition,we examine the innovative strategy of integrating drug repurposing with nanotechnology to enhance topical drug delivery.We also emphasize the critical role that repurposed drugs can play when used as part of a combination therapy regimen.To conclude,we outline the challenges associated with repurposing drugs and consider the future prospects of these repurposed drugs transitioning into clinical application.

关键词： drugs integrating spite

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Hybrid treatment of varied orthodontic appliances for a patient with skeletal class II and temporomandibular joint disorders:A case report and review of literature

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World Journal of Clinical Cases 2024年第2期12卷 431-442页

作者： Tong Lu Li Mei bao-Chao Li Zi-Wei huang huang Li Department of Orthodontics Nanjing Stomatological HospitalThe Affiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008Jiangsu ProvinceChina Discipline of Orthodontics Department of Oral ScienceFaculty of DentistryUniversity of OtagoDunedin 9016New Zealand

BACKGROUND The relation between orthodontic treatment and temporomandibular disorders(TMDs)is under debate;the management of TMD during orthodontic treatment has always been a challenge.If TMD symptoms occur during orthodontic treatment,an immediate pause of orthodontic adjustments is recommended;the treatment can resume when the symptoms are managed and stabilized.CASE SUMMARY This case report presents a patient(26-year-old,female)with angle class I,skeletal class II and TMDs.The treatment was a hybrid of clear aligners,fixed appliances and temporary anchorage devices(TADs).After 3 mo resting and treatment on her TMD,the patient’s TMD symptom alleviated,but her anterior occlusion displayed deep overbite.Therefore,the fixed appliances with TAD were used to correct the anterior deep-bite and level maxillary and mandibular deep curves.After the levelling,the patient showed dual bite with centric relation and maximum intercuspation discrepancy on her occlusion.After careful examination of temporomandibular joints(TMJ)position,the stable bite splint and Invisible Mandibular Advancement appliance were used to reconstruct her occlusion.Eventually,the improved facial appearance and relatively stable occlusion were achieved.The 1-year follow-up records showed there was no obvious change in TMJ morphology,and her occlusion was stable.CONCLUSION TMD screening and monitoring is of great clinical importance in the TMD susceptible patients.Hybrid treatment with clear aligners and fixed appliances and TADs is an effective treatment modality for the complex cases.

关键词： Temporomandibular disorder Skeletal class II Deep overbite Dual bite Invisible mandibular advancement appliance Case report

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A Review of Type 1 and Type 2 Intraductal Papillary Neoplasms of the Bile Duct

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Current Medical Science 2024年第3期44卷 485-493页

作者： Xia-hui huang Tian-xiang CHEN Hong-liang LIU ming-wen huang Department of General Surgery The Second Affiliated Hospital of Nanchang UniversityNanchang330006China

Intraductal papillary neoplasm of the bile duct(IPNB)is a heterogeneous disease similar to intraductal papillary mucinous neoplasm of the pancreas.These lesions have been recognized as one of the three major precancerous lesions in the biliary tract since 2010.In 2018,Japanese and Korean pathologists reached a consensus,classifying IPNBs into type l and type 2 IPNBs.IPNBs are more prevalent in male patients in East Asia and are closely related to diseases such as cholelithiasis and schistosomiasis.From a molecular genetic perspective,IPNBs exhibit early genetic variations,and different molecular pathways may be involved in the tumorigenesis of type 1 and type 2 IPNBs.The histological subtypes of IPNBs include gastric,intestinal,pancreaticobiliary,or oncocytic subtypes,but type 1 IPNBs typically exhibit more regular and well-organized histological features than type 2 IPNBs and are more commonly found in the intrahepatic bile ducts with abundant mucin.Due to the rarity of these lesions and the absence of specific clinical and laboratory features,imaging is crucial for the preoperative diagnosis of IPNB,with local bile duct dilation and growth along the bile ducts being the main imaging features.Surgical resection remains the optimal treatment for IPNBs,but negative bile duct margins and the removal of lymph nodes in the hepatic hilum significantly improve the postoperative survival rates for patients with IPNBs.

关键词： intraductal papillary neoplasm of the bile duct subclassification neoplasms precancerous tissue prognosis

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Assessment of Wet Season Precipitation in the Central United States by the Regional Climate Simulation of the WRFG Member in NARCCAP and Its Relationship with Large-Scale Circulation Biases

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Advances in Atmospheric Sciences 2024年第4期41卷 619-638页

作者： Yating ZHAO ming XUE Jing JIANG Xiao-ming HU Anning huang School of Atmospheric Sciences Nanjing UniversityNanjing 210023China Center for Analysis and Prediction of Storms and School of Meteorology The University of OklahomaNorman 73072U.S.A

Assessment of past-climate simulations of regional climate models(RCMs)is important for understanding the reliability of RCMs when used to project future regional climate.Here,we assess the performance and discuss possible causes of biases in a WRF-based RCM with a grid spacing of 50 km,named WRFG,from the North American Regional Climate Change Assessment Program(NARCCAP)in simulating wet season precipitation over the Central United States for a period when observational data are available.The RCM reproduces key features of the precipitation distribution characteristics during late spring to early summer,although it tends to underestimate the magnitude of precipitation.This dry bias is partially due to the model’s lack of skill in simulating nocturnal precipitation related to the lack of eastward propagating convective systems in the simulation.Inaccuracy in reproducing large-scale circulation and environmental conditions is another contributing factor.The too weak simulated pressure gradient between the Rocky Mountains and the Gulf of Mexico results in weaker southerly winds in between,leading to a reduction of warm moist air transport from the Gulf to the Central Great Plains.The simulated low-level horizontal convergence fields are less favorable for upward motion than in the NARR and hence,for the development of moist convection as well.Therefore,a careful examination of an RCM’s deficiencies and the identification of the source of errors are important when using the RCM to project precipitation changes in future climate scenarios.

关键词： NARCCAP Central United States precipitation low-level jet large-scale environment diurnal variation

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Pre-MASLD:Should it be defined separately?

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 1-3页

作者： Hang-Kai huang You-ming Li Cheng-Fu Xu Department of Gastroenterology Zhejiang Provincial Clinical Research Center for Digestive Diseasesthe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases,yet it has not received sufficient attention[1].Over the past two decades,the overall global prevalence of NAFLD has risen from 25%to 37%[2].The disease burden of NAFLD is fueled by the epidemic of obesity and diabetes[3].It is estimated that more than half of patients with diabetes have NAFLD.

关键词： NAFLD liver diseases

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