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Prevalence of gene mutations in a Chinese 46,XY disorders of sex development cohort detected by targeted next-generation sequencing

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Asian Journal of Andrology 2021年第1期23卷 69-73页

作者： Bing-Qing Yu Zhao-Xiang Liu yin-jie gao Xi Wang Jiang-Feng Mao Min Nie Xue-Yan Wu NHC Key Laboratory of Endocrinology Department of EndocrinologyPeking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100730China

46,XY disorders of sex development(DSD)is characterized by incomplete masculinization genitalia,with gonadal dysplasia and with/without the presence of Mullerian structures.At least 30 genes related to 46,XY DSD have been found.However,the clinical phenotypes of patients with different gene mutations overlap,and accurate diagnosis relies on gene sequencing technology.Therefore,this study aims to determine the prevalence of pathogenic mutations in a Chinese cohort with 46,XY DSD by the targeted nextgeneration sequencing(NGS)technology.Eighty-seven 46,XY DSD patients were enrolled from the Peking Union Medical College Hospital(Beijing,China).A total of fifty-four rare variants were identified in 60 patients with 46,XY DSD.The incidence of these rare variants was approximately 69.0%(60/87).Twenty-five novel variants and 29 reported variants were identified.Based on the American College of Medical Genetics and Genomics(ACMG)guidelines,thirty-three variants were classified as pathogenic or likely pathogenic variants and 21 variants were assessed as variants of uncertain significance.The overall diagnostic rate was about 42.5%based on the pathogenic and likely pathogenic variants.Androgen receptor{AR),steroid 5-alpha-reductase 2(SRD5A2)and nuclear receptor subfamily 5 Group A member 1(NR5A1)gene variants were identified in 21,13 and 13 patients,respectively.The incidence of these three gene variants was about 78.3%(47/60)in patients with rare variants.It is concluded that targeted NGS is an effective method to detect pathogenic mutations in 46,XY DSD patients and AR,SRD5A2,and NR5A1 genes were the most common pathogenic genes in our cohort.

关键词： 46,XY disorders of sex development mutations targeted next-generation sequencing

Gonadotropin treatment for male partial congenital hypogonadotropic hypogonadism in Chinese patients

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Asian Journal of Andrology 2020年第4期22卷 390-395页

作者： Ming Hao Min Nie Bing-Qing Yu yin-jie gao Xi Wang Wan-Lu Ma Qi-Bin Huang Rui Zhang Jiang-Feng Mao Xue-Yan Wu NHC Key laboratory of Endocrinolog Peking Union Medical College HospitalDepartment of EndocrinologyPeking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100730China Department of Endocrinology The First Affiliated Hospital of Harbin Medical UniversityHarbin 150001China

Partial congenital hypogonadotropic hypogonadism(PCHH)is caused by an insufficiency in,but not a complete lack of,gonadotropin secretion.This leads to reduced testosterone production,mild testicular enlargement,and partial pubertal development.No studies have shown the productivity of spermatogenesis in patients with PCHH.We compared the outcomes of gonadotropin-induced spermatogenesis between patients with PCHH and those with complete congenital hypogonadotropic hypogonadism(CCHH).This retrospective study included 587 patients with CHH who were treated in Peking Union Medical College Hospital(Beijing,China)from January 2008 to September 2016.A total of 465 cases were excluded from data analysis for testosterone or gonadotropin-releasing hormone treatment,cryptorchidism,poor compliance,or incomplete medical data.We defined male patients with PCHH as those with a testicular volume of≥4 ml and patients with a testicular volume of<4 ml as CCHH.A total of 122 compliant,noncryptorchid patients with PCHH or CCHH received combined human chorionic gonadotropin and human menopausal gonadotropin and were monitored for 24 months.Testicular size,serum luteinizing hormone levels,follicle-stimulating hormone levels,serum total testosterone levels,and sperm count were recorded at each visit.After gonadotropin therapy,patients with PCHH had a higher spermatogenesis rate(92.3%)than did patients with CCHH(74.7%).During 24-month combined gonadotropin treatment,the PCHH group took significantly less time to begin producing sperm compared with the CCHH group(median time:11.7 vs 17.8 months,P<0.05).In conclusion,after combined gonadotropin treatment,patients with PCHH have a higher spermatogenesis success rate and sperm concentrations and require shorter treatment periods for sperm production.

关键词： gonadotropin treatment partial congenital hypogonadotropic hypogonadism spermatogenesis

Modelling and validation of flash flood inundation in drylands

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Journal of Geographical Sciences 2024年第1期34卷 185-200页

作者： gao Dan yin jie WANG Dandan YANG Yuhan LU Yi CHEN Ruishan School of Geographic Sciences East China Normal UniversityShanghai 200241China Key Laboratory of Geographic Information Science of Ministry of Education East China Normal UniversityShanghai 200241China National Disaster Reduction Center of China Ministry of Emergency Management of People's Republic of ChinaBeijing 100124China School of Design Shanghai Jiao Tong UniversityShanghai 200240China

In the context of climate change and human activities,flood disasters in arid mountainous areas have become increasingly frequent,and seriously threatened the safety of people's lives and property.Rapid and accurate flash flood inundation modelling is an essential foundational research area,which can aid in the reduction of casualties and the minimization of disaster losses;however,this modelling is also very difficult,and models need to be urgently developed to address flash flood forecasting and warnings.The objective of this study is to construct a numerical modelling method for flash floods in drylands.Based on a 2D high-resolution flood numerical model(Flood Map-Hydro Inundation2D),we hindcasted the dynamic process of flash flooding and show the spatio-temporal characteristics of flash flood inundation for the“8·18”flash flood disaster that occurred in Datong county,Qinghai province.The results showed that the model output effectively agreed with the observed inundation after the event in terms of both spatial extent and temporal process.Extensive flooding mainly occurred between 00:00 and 01:00 on August 18,2022.Qingshan,Hejiazhuang and Longwo villages were affected most heavily.We further conducted model sensitivity analysis and found that the model was highly sensitive to both roughness and hydraulic conductivity in drylands,and the effect of hydraulic conductivity was more pronounced.Our study confirmed the good performance of our model for the simulation of flash flooding in arid areas and provides a potential method for flash flood assessment and management in arid areas.

关键词： flash flood numerical modelling arid areas Datong county Flood Map-Hydro Inundation2D

Biomaterials-based anti-inflammatory treatment strategies for Alzheimer's disease

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Neural Regeneration Research 2024年第1期19卷 100-115页

作者： Jianjian Chu Weicong Zhang Yan Liu Baofeng Gong Wenbo Ji Tong yin Chao gao Danqi Liangwen Mengqi Hao Cuimin Chen Jianhua Zhuang jie gao You yin Department of Neurology Second Affiliated Hospital(Shanghai Changzheng Hospital)of Naval Medical UniversityShanghaiChina School of Pharmacy University College LondonLondonUK Department of Clinical Pharmacy Xinhua HospitalShanghai Jiao Tong University School of MedicineClinical Pharmacy Innovation InstituteShanghai Jiao Tong University School of MedicineShanghaiChina School of Health Science and Engineering University of Shanghai for Science and TechnologyShanghaiChina Changhai Clinical Research Unit Shanghai Changhai HospitalNaval Medical UniversityShanghaiChina

The current therapeutic drugs for Alzheimer's disease only improve symptoms,they do not delay disease progression.Therefo re,there is an urgent need for new effective drugs.The underlying pathogenic factors of Alzheimer's disease are not clear,but neuroinflammation can link various hypotheses of Alzheimer's disease;hence,targeting neuroinflammation may be a new hope for Alzheimer's disease treatment.Inhibiting inflammation can restore neuronal function,promote neuro regeneration,reduce the pathological burden of Alzheimer's disease,and improve or even reverse symptoms of Alzheimer's disease.This review focuses on the relationship between inflammation and various pathological hypotheses of Alzheimer's disease;reports the mechanisms and characteristics of small-molecule drugs(e.g.,nonsteroidal anti-inflammatory drugs,neurosteroids,and plant extracts);macromolecule drugs(e.g.,peptides,proteins,and gene therapeutics);and nanocarriers(e.g.,lipid-based nanoparticles,polymeric nanoparticles,nanoemulsions,and inorganic nanoparticles)in the treatment of Alzheimer's disease.The review also makes recommendations for the prospective development of anti-inflammatory strategies based on nanocarriers for the treatment of Alzheimer's disease.

关键词： Alzheimer's disease anti-inflammation blood-brain barrier drug delivery microglia nanoparticles neuroinflammation plant extracts

Dual ligand-targeted Pluronic P123 polymeric micelles enhance the therapeutic effect of breast cancer with bone metastases

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Oncology Research 2024年第4期32卷 769-784页

作者： HUAN gao jie ZHANG TONY GKLEIJN ZHAOYONG WU BING LIU YUJIN MA BAOYUE DING DONGFENG yin Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics Department of PharmaceuticsCollege of MedicineJiaxing UniversityJiaxing314001China Department of Pharmacy The General Hospital of Xinjiang Military RegionUrumqi830000China Department of Pathology and Medical Biology University Medical Center GroningenUniversity of GroningenGroningen9713 GZThe Netherlands Department of Pathology Laboratory of Experimental OncologyErasmus MCRotterdam3015 GDThe Netherlands Department of Pharmacy Jiaxing Maternal and Child Health Care HospitalAffiliated Hospital of Jiaxing UniversityJiaxing314001China Qinghai Enlu Biotechnology Co. Ltd.Haidong810700China

Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival.The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect.To improve the treatment efficacy,we developed Pluronic P123(P123)-based polymeric micelles dually decorated with alendronate(ALN)and cancer-specific phage protein DMPGTVLP(DP-8)for targeted drug delivery to breast cancer bone metastases.Doxorubicin(DOX)was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity(3.44%).The DOX-loaded polymeric micelles were spherical,123 nm in diameter on average,and exhibited a narrow size distribution.The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release.The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells.Rapid binding of the micelles to hydroxyapatite(HA)microparticles indicated their high affinity for bone.P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model.In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity.In conclusion,our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.

关键词： Pluronic micelles Targeted nanotherapeutics Nanoparticulate drug delivery system Breast cancer with bone metastasis Therapeutic efficacy

Honokiol Prevents Intestinal Barrier Dysfunction in Mice with Severe Acute Pancreatitis and Inhibits JAK/STAT1 Pathway and Acetylation of HMGB1

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Chinese Journal of Integrative Medicine 2024年第6期30卷 534-542页

作者： LI jie CHEN Ya-feng gao Lei LI Yi-jie FENG Dian-xu Department of General Surgery Putuo HospitalShanghai University of Traditional Chinese MedicineShanghai200062China

Objective To investigate the effect of honokiol(HON)and the role of high-mobility group protein B1(HMGB1)on the pathogenesis of severe acute pancreatitis(SAP).Methods Thirty mice were numbered according to weight,and randomly divided into 5 groups using a random number table,including control,SAP,SAP and normal saline(SAP+NS),SAP and ethyl pyruvate(SAP+EP),or SAP+HON groups,6 mice in each group.Samples of pancreas,intestine,and blood were collected 12 h after SAP model induction for examination of pathologic changes,immune function alterations by enzyme linked immunosorbent assay(ELISA),and Western blot.In vitro experiments,macrophages were divided into 5 groups,the control,lipopolysaccharide(LPS),LPS+DMSO(DMSO),LPS+anti-HMGB1 monoclonal antibody(mAb),and LPS+HON groups.The tight connection level was determined by transmission electron microscopy and fluorescein isothiocyanate-labeled.The location and acetylation of HMGB1 were measured by Western blot.Finally,pyridone 6 and silencing signal transducer and activator of the transcription 1(siSTAT1)combined with honokiol were added to determine whether the Janus kinase(JAK)/STAT1 participated in the regulation of honokiol on HMGB1.The protein expression levels of HMGB1,JAK,and STAT1 were detected using Western blot.Results Mice with SAP had inflammatory injury in the pancreas,bleeding of intestinal tissues,and cells with disrupted histology.Mice in the SAP+HON group had significantly fewer pathological changes.Mice with SAP also had significant increases in the serum levels of amylase,lipase,HMGB1,tumor necrosis factor-α,interleukin-6,diamine oxidase,endotoxin-1,and procalcitonin.Mice in the SAP+HON group did not show these abnormalities(P<0.01).Studies of Caco-2 cells indicated that LPS increased the levels of occludin and claudin-1 as well as tight junction permeability,decreased the levels of junctional adhesion molecule C,and elevated intercellular permeability(P<0.01).HON treatment blocked these effects.Studies of macrophages indicated that LPS led to low nucle

关键词： severe acute pancreatitis intestinal barrier dysfunction honokiol high-mobility group protein B1 Januskinase signal transducerand activatorof transcription1

DNA Damage-driven Inflammatory Cytokines:Reprogramming of Tumor Immune Microenvironment and Application of Oncotherapy

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Current Medical Science 2024年第2期44卷 261-272页

作者： Meng-jie WANG Yu XIA Qing-lei gao Department of Obstetrics and Gynecology National Clinical Research Center for Obstetrics and GynecologyTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Key Laboratory of Cancer Invasion and Metastasis(Ministry of Education) Hubei Key Laboratory of Tumor Invasion and MetastasisTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

DNA damage occurs across tumorigenesis and tumor development.Tumor intrinsic DNA damage can not only increase the risk of mutations responsible for tumor generation but also initiate a cellular stress response to orchestrate the tumor immune microenvironment(TIME)and dominate tumor progression.Accumulating evidence documents that multiple signaling pathways,including cyclic GMP-AMP synthase-stimulator of interferon genes(cGAS-STING)and ataxia telangiectasia-mutated protein/ataxia telangiectasia and Rad3-related protein(ATM/ATR),are activated downstream of DNA damage and they are associated with the secretion of diverse cytokines.These cytokines possess multifaced functions in the anti-tumor immune response.Thus,it is necessary to deeply interpret the complex TIME reshaped by damaged DNA and tumor-derived cytokines,critical for the development of effective tumor therapies.This manuscript comprehensively reviews the relationship between the DNA damage response and related cytokines in tumors and depicts the dual immunoregulatory roles of these cytokines.We also summarize clinical trials targeting signaling pathways and cytokines associated with DNA damage and provide future perspectives on emerging technologies.

关键词： DNA damage tumor immune microenvironment inflammatory cytokines cancer therapy

Identification of a novel inflammatory-related gene signature to evaluate the prognosis of gastric cancer patients

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 945-967页

作者： Jia-Li Hu Mei-Jin Huang Halike Halina Kun Qiao Zhi-Yuan Wang Jia-jie Lu Cheng-Liang yin Feng gao Department of Gastroenterology People's Hospital of Xinjiang Uygur Autonomous RegionUrumqi 830001Xinjiang Uygur Autonomous RegionChina Xinjiang Clinical Research Center for Digestive Disease Urumqi 830001Xinjiang Uygur Autonomous RegionChina Department of Oncology 920th Hospital of PLA Joint Logistics Support ForceKunming 650032Yunnan ProvinceChina Faculty of Medicine Macao University of Science and TechnologyMacao 999078China

BACKGROUND Gastric cancer(GC)is a highly aggressive malignancy with a heterogeneous nature,which makes prognosis prediction and treatment determination difficult.Inflammation is now recognized as one of the hallmarks of cancer and plays an important role in the aetiology and continued growth of tumours.Inflammation also affects the prognosis of GC patients.Recent reports suggest that a number of inflammatory-related biomarkers are useful for predicting tumour prognosis.However,the importance of inflammatory-related biomarkers in predicting the prognosis of GC patients is still unclear.AIM To investigate inflammatory-related biomarkers in predicting the prognosis of GC patients.was constructed using the least absolute shrinkage and selection operator Cox regression model based on the GEO database.GC patients from the GSE26253 cohort were used for validation.Univariate and multivariate Cox analyses were used to determine the independent prognostic factors,and a prognostic nomogram was established.The calibration curve and the area under the curve based on receiver operating characteristic analysis were utilized to evaluate the predictive value of the nomogram.The decision curve analysis results were plotted to quantify and assess the clinical value of the nomogram.Gene set enrichment analysis was performed to explore the potential regulatory pathways involved.The relationship between tumour immune infiltration status and risk score was analysed via Tumour Immune Estimation Resource and CIBERSORT.Finally,we analysed the association between risk score and patient sensitivity to commonly used chemotherapy and targeted therapy agents.RESULTS A prognostic model consisting of three inflammatory-related genes(MRPS17,GUF1,and PDK4)was constructed.Independent prognostic analysis revealed that the risk score was a separate prognostic factor in GC patients.According to the risk score,GC patients were stratified into high-and low-risk groups,and patients in the high-risk group had significantly worse prognoses according to age

关键词： Gastric cancer Inflammation Immune infiltration Prognosis signature Subt

Advances of Electrochemical and Electrochemiluminescent Sensors Based on Covalent Organic Frameworks

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Nano-Micro Letters 2024年第2期16卷 395-422页

作者： Yue Cao Ru Wu Yan‑Yan gao Yang Zhou Jun‑jie Zhu Key Laboratory for Organic Electronics and Information Displays(KLOEID)and Institute of Advanced Materials(IAM) Nanjing University of Posts and Telecommunications(NJUPT)Nanjing 210023People’s Republic of China State Key Laboratory of Analytical Chemistry for Life Science School of Chemistry and Chemical EngineeringNanjing UniversityNanjing 210023People’s Republic of China

Covalent organic frameworks(COFs),a rapidly developing category of crystalline conjugated organic polymers,possess highly ordered structures,large specific surface areas,stable chemical properties,and tunable pore microenvironments.Since the first report of boroxine/boronate ester-linked COFs in 2005,COFs have rapidly gained popularity,showing important application prospects in various fields,such as sensing,catalysis,separation,and energy storage.Among them,COFs-based electrochemical(EC)sensors with upgraded analytical performance are arousing extensive interest.In this review,therefore,we summarize the basic properties and the general synthesis methods of COFs used in the field of electroanalytical chemistry,with special emphasis on their usages in the fabrication of chemical sensors,ions sensors,immunosensors,and aptasensors.Notably,the emerged COFs in the electrochemiluminescence(ECL)realm are thoroughly covered along with their preliminary applications.Additionally,final conclusions on state-of-the-art COFs are provided in terms of EC and ECL sensors,as well as challenges and prospects for extending and improving the research and applications of COFs in electroanalytical chemistry.

关键词： Covalent organic frameworks Electrochemistry Electrochemiluminescence Sensors