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Senktide blocks aberrant RTN3 interactome to retard memory decline and tau pathology in social isolated Alzheimer’s disease mice

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Protein & Cell 2024年第4期15卷 261-284页

作者： He-Zhou Huang Wen-Qing Ai Na Wei Ling-Shuang Zhu Zhi-Qiang Liu Chao-Wen Zhou Man-Fei Deng Wen-Tao Zhang Jia-Chen Zhang Chun-Qing Yang Ya-Zhuo Hu Zhi-Tao Han Hong-Hong Zhang Jian-Jun Jia Jing Wang Fang-Fang Liu Ke Li Qi Xu Mei Yuan Hengye Man Ziyuan Guo Youming Lu Kai Shu Ling-Qiang Zhu Dan Liu department of Pathophysiology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China department of Medical Genetics School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China department of Pathology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450002China department of Pathology School of Basic MedicineZhengzhou UniversityZhengzhou 450002China The Second Affiliated Hospital Department of NeurologyHengyang Medical SchoolUniversity of South ChinaHengyang 421001China Beijing Key Laboratory of Aging and Geriatrics National Clinical Research Center for Geriatric DiseaseInstitute of GeriatricsChinese PLA General Hospital and Chinese PLA Medical AcademyBeijing 100853China department of Neurosurgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China department of Neurology Union HospitalHuazhong University of Science and TechnologyWuhan 430022China department of Biology Boston UniversityBostonMA 02215USA Center for Stem Cell and Organoid medicine(CuSTOM) Division of Developmental BiologyCincinnati Children’s Hospital Medical CenterCincinnatiOH 45229USA

Sporadic or late-onset Alzheimer’s disease(LOAD)accounts for more than 95%of Alzheimer’s disease(AD)cases without any family *** genome-wide association studies have identified associated risk genes and loci for LOAD,numerous studies suggest that many adverse environmental factors,such as social isolation,are associated with an increased risk of ***,the underlying mechanisms of social isolation in AD progression remain *** the current study,we found that 7 days of social isolation could trigger pattern separation impairments and presynaptic abnormalities of the mossy fibre-CA3 circuit in AD *** also revealed that social isolation disrupted histone acetylation and resulted in the downregulation of 2 dentate gyrus(DG)-enriched miRNAs,which simultaneously target reticulon 3(RTN3),an endoplasmic reticulum protein that aggregates in presynaptic regions to disturb the formation of functional mossy fibre boutons(MFBs)by recruiting multiple mitochondrial and vesicle-related ***,the aggregation of RTN3 also recruits the PP2A B subunits to suppress PP2A activity and induce tau hyperphosphorylation,which,in turn,further elevates RTN3 and forms a vicious ***,using an artificial intelligence-assisted molecular docking approach,we determined that senktide,a selective agonist of neurokinin3 receptors(NK3R),could reduce the binding of RTN3 with its ***,application of senktide in vivo effectively restored DG circuit disorders in socially isolated AD *** together,our findings not only demonstrate the epigenetic regulatory mechanism underlying mossy fibre synaptic disorders orchestrated by social isolation and tau pathology but also reveal a novel potential therapeutic strategy for AD.

关键词： Alzheimer’s disease memory impairment synaptic disorder tau pathology

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Patient-centered care in diabetes care-concepts,relationships and practice

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World Journal of Diabetes 2024年第7期15卷 1417-1429页

作者： Tsung-Tai Chen Wei-Chih Su Mei-I Liu department of Public Health College of MedicineFu Jen Catholic UniversityNew Taipei 24205Taiwan department of Gastroenterology Taipei Tzu-Chi HospitalNew Taipei 23142Taiwan department of Pediatric Endocrinology Mackay Children's HospitalTaipei 10449Taiwan

We still do not have comprehensive knowledge of which framework of patientcentered care(PCC)is appropriate for diabetes care,which elements of PCC are evidence-based,and the mechanism by which PCC elements are associated with outcomes through *** this review,we elaborate on these *** found that for diabetes care,PCC elements such as autonomy support(patient individuality),cooperation and collaboration(system-level approach),communication and education(behavior change techniques),emotional support(biopsychosocial approach),and family/other involvement and support are critically *** of these factors are directly associated with different patient outcomes and indirectly associated with outcomes through patient *** present the practical implications of these PCC elements.

关键词： Diabetes mellitus Patient-centered care Autonomy support Patient activation Patient adherence

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Protective and Adverse Roles of DDX3X in Different Cell Types in Nonalcoholic Steatohepatitis Progression

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Research 2024年第3期6卷 561-574页

作者： Suzhen Yang Lin Zhou Tianming Zhao Hanlong Zhu Tingting Luo Kang Jiang Xiaoxiao Shi Chunyan Chen Han Zhang Si Zhao Xiaoping Zou Yuzheng Zhuge Fangyu Wang Lei Wang Mingzuo Jiang Bing Xu department of Gastroenterology the Affiliated Drum Tower Hospital of Nanjing University Medical SchoolJiangsuNanjing210002China. department of Gastroenterology and Hepatology the Affiliated Jinling Hospital of Nanjing University Medical SchoolJiangsuNanjing210002China School of medicine Northwest UniversityShaanxiXi’an710069China. department of Gastroenterology Nanjing Drum Tower HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeJiangsuNanjing210008China.

Persistent hepatic cellular metabolic stress and liver inflammatory stimuli are key signatures of nonalcoholic steatohepatitis(NASH).DDX3X is a vital molecule involved in cell fate decisions in both pro-survival stress granule(SG)and pro-death NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome assembly in response to stress ***,the role of DDX3X in NASH remains *** characterized the cell type-specific roles of DDX3X in *** liver tissues from NASH patients and normal control subjects were collected to assess DDX3X expression and *** steatohepatitis models were constructed by feeding macrophage-specific DDX3X knockout(DDX3^(XΔMφ)),hepatocyte-specific DDX3X knockout(DDX3X^(Δhep)),and wild-type control(DDX3X^(fl/fl))mice a high-fat and high-cholesterol(HFHC)diet,a methionine-and choline-deficient(MCD)diet,and a high-fat/high-iron/high-fructose/high-cholesterol,low-methionine,and choline-deficient(HFHIHFHC-MCD)*** study demonstrated that DDX3X was predominantly expressed in macrophages and hepatocytes in control liver tissues,and its expression was down-regulated in patients or mice with *** to DDX3X^(fl/fl) littermates,DDX3^(XΔMφ)mice showed improved liver histology in nutritional steatohepatitis *** of macrophage DDX3X inhibited NLRP3 inflammasome-mediated pyroptosis,causing anti-inflammatory M2 polarization and alleviating hepatocyte steatohepatitic ***3X^(Δhep) mice developed marked steatohepatitis in multiple nutritional steatohepatitis models compared to DDX3X^(fl/fl) ***3X-deleted hepatocytes showed impaired SG assembly,leading to increased sensitivity and intolerance to metabolic stimulation and resultant *** conclusion,DDX3X plays opposite roles in different cell types during the progression of NASH.A better understanding of the cell-specific differences in the crosstalk between SG formation and NLRP3 activation is crucial for developing pr

关键词： NLRP3 impaired inhibited

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CGG repeat expansion in LOC642361/NUTM2B-AS1 typically presents as oculopharyngodistal myopathy

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Journal of Genetics and Genomics 2024年第2期51卷 184-196页

作者： Yan Shi Chunyan Cao Yiheng Zeng Yuanliang Ding Long Chen Fuze Zheng Xuejiao Chen Fanggui Zhou Xiefeng Yang Jinjing Li Liuqing Xu Guorong Xu Minting Lin Hiroyuki Ishiura Shoji Tsuji Ning Wang Zhiqiang Wang Wan-Jin Chen Kang Yang department of Neurology and Institute of Neurology of First Affiliated Hospital Institute of NeuroscienceFujian Key Laboratory of Molecular NeurologyFujian Medical UniversityFuzhouFujian 350005China department of Neurology National Regional Medical CenterBinhai Campus of the First Affiliated HospitalFujian Medical UniversityFuzhouFujian 350212China The First Affiliated Hospital College of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan 471000China department of Neurology Zhangzhou Municipal Hospital of Fujian Province and Zhangzhou Affiliated Hospital of Fujian Medical UniversityZhangzhouFujian 363000China department of Neurology Jian'ou Municipal Hospital of Fujian ProvinceJian'ouFujian 353100China department of Radiology First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian 350005China department of Neurology Graduate School of MedicineThe University of TokyoTokyo 113-8655Japan department of Neurology Okayama University Graduate School of MedicineDentistry and Pharmaceutical SciencesOkayama 700-8558Japan Institute of Medical Genomics International University of Health and WelfareChiba 286-0048Japan

CGG repeat expansions in LOC642361/NUTM2B-AS1 have recently been identified as a cause of oculopharyngeal myopathy with ***,since only three patients from a single family were reported,it remains unknown whether their clinicopathological features are typical for CGG repeat expansions in LOC642361/***,using repeat-primed-polymerase chain reaction and long-read sequencing,we identify 12 individuals from 3 unrelated families with CGG repeat expansions in LOC642361/NUTM2B-AS1,typically presenting with oculopharyngodistal *** CGG repeat expansions range from 161 to 669 repeat *** of the patients present with ptosis,restricted eye movements,dysphagia,dysarthria,and diffuse limb muscle *** one patient shows T2-weighted hyperintensity in the cerebellar white matter surrounding the deep cerebellar nuclei on brain magnetic resonance *** biopsies from three patients show a myopathic pattern and rimmed *** of muscle biopsies suggest that CGG repeat expansions in LOC642361/NUTM2B-AS1 may deleteriously affect aggrephagic capacity,suggesting that RNA toxicity and mitochondrial dysfunction may contribute to *** study thus expands the phenotypic spectrum for the CGG repeat expansion of LOC642361/NUTM2B-AS1 and indicates that this genetic variant typically manifests as oculopharyngodistal myopathy with chronic myopathic changes with rimmed vacuoles and filamentous intranuclear inclusions in muscle fibers.

关键词： Oculopharyngeal myopathy with leukoencephalopathy Oculopharyngodistal myopathy CGG repeat expansion Rimmed vacuoles

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Deleterious variants in RNF111 impair female fertility and induce premature ovarian insufficiency in humans and mice

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Science China(Life Sciences) 2024年第7期67卷 1325-1337页

作者： Chengcheng Song Yingying Qin Yan Li Bingyi Yang Ting Guo Wenqing Ma Dian Xu Keyan Xu Fangfang Fu Li Jin Yanhua Wu Shuyan Tang Xiaojun Chen Feng Zhang Obstetrics and Gynecology Hospital State Key Laboratory of Genetic EngineeringInstitute of Medical Genetics and GenomicsFudan UniversityShanghai 200011China Human Phenome Institute Zhangjiang Fudan International Innovation CenterFudan UniversityShanghai 201203China Center for Reproductive medicine Cheeloo College of MedicineShandong UniversityJinan 250021China State Key Laboratory of Reproductive medicine and Offspring Health Key Laboratory of Reproductive Endocrinology of Ministry of EducationNational Research Center for Assisted Reproductive Technology and Reproductive GeneticsShandong Key Laboratory of Reproductive MedicineShandong Provincial Clinical Research Center for Reproductive HealthShandong UniversityJinan 250021China department of Obstetrics and Gynecology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China National Demonstration Center for Experimental Biology Education School of Life SciencesFudan UniversityShanghai 200433China department of Gynecology the Tenth People’s Hospital of Tongji UniversityShanghai 200072China Soong Ching Ling Institute of Maternity and Child Health International Peace Maternity and Child Health Hospital of China Welfare InstituteShanghai 200030China

Premature ovarian insufficiency(POI)is a heterogeneous female disorder characterized by the loss of ovarian function before the age of *** represents a significant detriment to female ***,the known POI-causative genes currently account for only a fraction of *** elucidate the genetic factors underlying POI,we conducted whole-exome sequencing on a family with three fertile POI patients and identified a deleterious missense variant in *** a subsequent replication study involving 1,030 POI patients,this variant was not only confirmed but also accompanied by the discovery of three additional predicted deleterious RNF111 *** variants collectively account for eight cases,representing 0.78%of the study cohort.A further study involving 500 patients with diminished ovarian reserve also identified two additional RNF111 ***,RNF111 encodes an E3 ubiquitin ligase with a regulatory role in the TGF-β/BMP signaling *** analysis revealed that RNF111/RNF111 is predominantly expressed in the oocytes of mice,monkeys,and *** further investigate the functional implications of RNF111 variants,we generated two mouse models:one with a heterozygous missense mutation(Rnf111+/M)and another with a heterozygous null mutation(Rnf111^(+/-)).Both mouse models exhibited impaired female fertility,characterized by reduced litter sizes and small ovarian ***,RNA-seq and quantitative proteomics analysis unveiled that Rnf111 haploinsufficiency led to dysregulation in female gonad development and negative regulation of the BMP signaling pathway within mouse *** conclusion,our findings strongly suggest that monoallelic deleterious variants in RNF111 can impair female fertility and induce POI in both humans and mice.

关键词： POI RNF111 female fertility ovarian reserve

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Novel subtype of obesity influencing the outcomes of sleeve gastrectomy:Familial aggregation of obesity

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World Journal of Gastroenterology 2024年第13期30卷 1887-1898页

作者： Ze-Yu Wang Yun-Fei Qu Tian-Ming Yu Zeng-Lin Liu Yu-Gang Cheng Ming-Wei Zhong San-Yuan Hu department of General Surgery The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan HospitalJinan 250000Shandong ProvinceChina department of Postgraduate Shandong First Medical University and Shandong Academy of Medical SciencesJinan 250000Shandong ProvinceChina department of General Surgery Shandong Provincial Qianfoshan HospitalCheeloo College of Medicine Shandong UniversityJinan 250000Shandong ProvinceChina State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese medicine Lunan Pharmaceutical Group Co.Ltd.Linyi 276005Shandong ProvinceChina

BACKGROUND Differences in the preoperative characteristics and weight loss outcomes after sleeve gastrectomy(SG)between patients with familial aggregation of obesity(FAO)and patients with sporadic obesity(SO)have not been *** To explore the impact of SG on weight loss and the alleviation of obesity-related comorbidities in individuals with *** A total of 193 patients with obesity who underwent SG were *** with FAO/SO were matched 1:1 by propensity score matching and were categorized into 4 groups based on the number of first-degree relatives with obesity(1 SO vs 1FAO,2SO vs 2FAO).The baseline characteristics,weight loss outcomes,prevalence of obesity-related comorbidities and incidence of major surgeryrelated complications were compared between *** We defined FAO as the presence of two or more first-degree relatives with *** with FAO did not initially show significant differences in baseline data,short-term postoperative weight loss,or obesity-related comorbidities when compared to patients with SO ***,distinctions between the two groups became evident at the two-year mark,with statistically significant differences in both percentage of total weight loss(P=0.006)and percentage of excess weight loss(P<0.001).The FAO group exhibited weaker remission of type 2 diabetes mellitus(T2DM)(P=0.031),hyperlipidemia(P=0.012),and non-alcoholic fatty liver disease(NAFLD)(P=0.003)as well as a lower incidence of acid reflux(P=0.038).CONCLUSION FAO patients is associated with decreased mid-to-long-term weight loss outcomes;the alleviation of T2DM,hyperlipidemia and NAFLD;and decreased incidence of acid reflux postoperatively.

关键词： Obesity Bariatric surgery Sleeve gastrectomy family history Weight loss

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Absent in melanoma 2 attenuates proliferation and migration and promotes apoptosis of human colorectal cancer cells by activating P38MAPK signaling pathway

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Oncology Research 2024年第2期32卷 353-360页

作者： ZHI ZHANG XIAOSONG LI YING ZHANG HAO ZHU ZHENGUO QIAO YANG LU XIUWEI MI HUIHUA CAO GENHAI SHEN SONGBING HE department of General Surgery Suzhou Ninth People’s HospitalSuzhou Ninth Hospital Affiliated to Soochow UniversitySuzhouChina Medical college of Nantong university NantongChina department of Gastroenterology Suzhou Ninth People’s HospitalSuzhou Ninth Hospital Affiliated to Soochow UniversitySuzhouChina department of General Surgery The First Affiliated Hospital of Soochow UniversitySuzhouChina department of Oncological Surgery Kunshan Traditional Hospital Affiliated to Nanjing University of Chinese MedicineKunshanChina

Colorectal cancer(CRC)stands among the top prevalent cancers worldwide and holds a prominent position as a major contributor to cancer-related mortality *** in melanoma 2(AIM2),a constituent of the interferoninducible hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeats protein family,contributes to both cancer progression and inflammasome *** this understanding,the precise biological functions and molecular mechanisms governed by AIM2 in CRC remain ***,this study endeavors to assess AIM2’s expression levels,explore its potential antitumor effects,elucidate associated cancer-related processes,and decipher the underlying signaling pathways in *** findings showed a reduced AIM2 expression in most CRC cell *** of AIM2 levels suppressed CRC cell proliferation and migration,altered cell cycle by inhibiting G1/S transition,and induced cell *** research uncovered the participation of P38 mitogen-activated protein kinase(P38MAPK)in AIM2-mediated modulation of CRC cell apoptosis and ***,our achievements distinctly underscored AIM2’s antitumor role in ***2 overexpression inhibited proliferation and migration and induced apoptosis of CRC cells via activating P38MAPK signaling pathway,indicating AIM2 as a prospective and novel therapeutic target for CRC.

关键词： Absent in melanoma 2 Proliferation Migration Apoptosis P38MAPK Colorectal cancer

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Effects of SARS-CoV-2 infection on incidence and treatment strategies of hepatocellular carcinoma in people with chronic liver disease

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World Journal of Hepatology 2024年第2期16卷 211-228页

作者： Lung-Yi Mak Matthew Shing Hin Chung Xue Li Francisco Tsz Tsun Lai Eric Yuk Fai Wan Celine Sze Ling Chui Franco Wing Tak Cheng Esther Wai Yin Chan Ching Lung Cheung Ivan Chi Ho Au Xi Xiong Wai-Kay Seto Man-Fung Yuen Carlos King Ho Wong Ian Chi Kei Wong department of medicine The University of Hong KongHong KongChina State Key Laboratory of Liver Research The University of Hong KongHong KongChina department of Pharmacology and Pharmacy The University of Hong KongHong KongChina Laboratory of Data Discovery for Health(D24H) Hong Kong Science and Technology ParkHong KongChina department of family medicine and Primary Care The University of Hong KongHong KongChina School of Nursing The University of Hong KongHong KongChina School of Public Health The University of Hong KongHong KongChina Research department of Practice and Policy University College LondonLondon WC1E 6BTUnited Kingdom Aston School of Pharmacy Aston UniversityBirmingham B47ETUnited Kingdom

BACKGROUND Chronic liver disease(CLD)was associated with adverse clinical outcomes among people with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)*** To determine the effects of SARS-CoV-2 infection on the incidence and treatment strategy of hepatocellular carcinoma(HCC)among patients with *** A retrospective,territory-wide cohort of CLD patients was identified from an electronic health database in Hong *** with confirmed SARS-CoV-2 infection[coronavirus disease 2019(COVID-19)+CLD]between January 1,2020 and October 25,2022 were identified and matched 1:1 by propensity-score with those without(COVID-19-CLD).Each patient was followed up until death,outcome event,or November 15,*** outcome was incidence of *** outcomes included all-cause mortality,adverse hepatic outcomes,and different treatment strategies to HCC(curative,non-curative treatment,and palliative care).Analyses were further stratified by acute(within 20 d)and post-acute(21 d or beyond)phases of SARS-CoV-2 *** rate ratios(IRRs)were estimated by Poisson regression *** Of 193589 CLD patients(>95%non-cirrhotic)in the cohort,55163 patients with COVID-19+CLD and 55163 patients with COVID-19-CLD were included after 1:1 propensity-score *** 249-d median follow-up,COVID-19+CLD was not associated with increased risk of incident HCC(IRR:1.19,95%CI:0.99-1.42,P=0.06),but higher risks of receiving palliative care for HCC(IRR:1.60,95%CI:1.46-1.75,P<0.001),compared to *** both acute and post-acute phases of infection,COVID-19+CLD were associated with increased risks of allcause mortality(acute:IRR:7.06,95%CI:5.78-8.63,P<0.001;post-acute:IRR:1.24,95%CI:1.14-1.36,P<0.001)and adverse hepatic outcomes(acute:IRR:1.98,95%CI:1.79-2.18,P<0.001;post-acute:IRR:1.24,95%CI:1.13-1.35,P<0.001),compared to *** Although CLD patients with SARS-CoV-2 infection were not associated with increased risk of HCC,they

关键词： SARS-CoV-2 infection Chronic liver disease Long COVID Post-COVID-19 syndrome Cirrhosis Hepatocellular carcinoma

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Microphallus early management in infancy saves adulthood sensual life:A comprehensive review

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World Journal of Clinical Pediatrics 2024年第2期13卷 16-37页

作者： Mohammed Al-Beltagi Nermin Kamal Saeed Adel Salah Bediwy Majed A Shaikh Reem Elbeltagi department of Pediatric Faculty of MedicineTanta UniversityTanta 31511Egypt department of Pediatric University Medical CenterKing Abdulla Medical CityArabian Gulf UniversityManama 26671Bahrain department of Pediatric University Medical CenterSulaiman Al Habib Medical GroupManama 26671Bahrain department of Medical Microbiology Section and Pathology Salmaniya Medical ComplexMinistry of HealthKingdom of BahrainManama 12Bahrain department of Medical Microbiology Section and Pathology Irish Royal College of SurgeonBusaiteen 15503Bahrain department of Pulmonology Faculty of MedicineTanta UniversityTanta 31527Egypt department of Pulmonology University Medical CenterKing Abdulla Medical CityArabian Gulf UniversityManama 26671Bahrain department of Pulmonology University Medical CenterSulaiman Al Habib Medical GroupManama 26671Bahrain department of Pediatrics Ibn Al Nafees HospitalManama 54533Bahrain department of medicine The Royal College of Surgeons in Ireland-BahrainBusiateen 15503Bahrain

Microphallus/Micropenis is a rare condition with significant physical and psychological implications for affected *** article comprehensively reviews micropenis,its etiology,epidemiology,and various treatment *** conducted a thorough literature review to collect relevant information on micropenis and microphallus,as well as related *** primary databases were PubMed,Medline,and Google *** searched for articles published in English between 2000 and *** analysis included 67 review articles,56 research studies,11 case reports,one guideline,and one *** search terms included"microphallus","micropenis","congenital hypogonadotropic hypogonadism","androgen insensitivity syndrome","pediatric management of micropenis","testosterone therapy",and"psychosocial implications of micropenis".We focused on diagnosing micropenis and related conditions,including hormonal assessments,medical and surgical treatment options,psychosocial and psychological well-being,sexual development of adolescents,and sociocultural influences on men's perceptions of penile ***,we explored parenting and family dynamics in cases of micropenis and disorders of sex development,implications of hormonal treatment in neonates,and studies related to penile augmentation procedures and their *** article highlights the importance of early diagnosis and intervention in addressing the physical and psychological well-being of individuals with *** procedures,such as penile lengthening and girth enhancement,and non-surgical approaches like hormonal therapy are *** significance of psychological support,education,and lifestyle modifications is *** management and comprehensive care are crucial for individuals with micropenis,from infancy to adolescence and beyond.A multidisciplinary approach involving urologists,endocrinologists,and mental health professionals is *** assessment of treatment e

关键词： Microphallus Micropenis Hypogonadism Children Adults Sensual life Testosterone therapy

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Pien Tze Huang Inhibits Migration and Invasion of Hepatocellular Carcinoma Cells by Repressing PDGFRB/YAP/CCN2 Axis Activity

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Chinese Journal of Integrative medicine 2024年第2期30卷 115-124页

作者： LUO Zhi-yi TIAN Qi CHENG Niang-mei LIU Wen-han YANG Ye CHEN Wei ZHANG Xiang-zhi ZHENG Xiao-yuan CHEN Ming-sheng ZHUANG Qiu-yu ZHAO Bi-xing LIU Cong-sheng LIU Xiao-long LI Qin WANG Ying-chao The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhou(350025)China Fujian Pien Tze Huang Enterprise Key Laboratory of Natural medicine Research and Development Zhangzhou Pien Tze Huang Pharmaceutical Co.Ltd.ZhangzhouFujian Province(363099)China college of Biological Science and Engineering and Mengchao Med-X Center Fuzhou UniversityFuzhou(350116)China department of Internal medicine Mengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhou(350025)China

Objective:To investigate the effects of Pien Tze Huang(PZH) on the migration and invasion of HCC cells and underlying molecular ***:Cell counting kit-8(CCK-8) was applied to evaluate the cell viabilities of SMMC-7721,SK-Hep-1,C3A and HL-7702(6 × 10^(3)cells/well) co-incubated with different concentrations of PZH(0,0.2,0.4,0.6,0.8 mg/mL) for 24 ***,wound healing assay,CCK-8and Annexin V-FITC/PI staining were conducted to investigate the effects of PZH on the migration,invasion,proliferation and apoptosis of SK-Hep-1 and SMMC-7721 cells(650 μg/mL for SK-Hep-1 cells and 330 μg/mL for SMMC-7721 cells),*** vivo,lung metastasis mouse model constructed by tail vein injection of HCC cells was used for evaluating the anti-metastasis function of ***-Hep-1 cells(10^(6)cells/200 μL per mice) were injected into B-NDG mice via tail *** 8 mice were randomly divided into PZH and control groups,4 mice in each *** 2-d inoculation,mice in the PZH group were administered with PZH(250 mg/kg,daily) and mice in the control group received only vehicle(PBS) from the 2nd day after xenograft to day *** analysis based on RNA-seq was subsequently used for deciphering anti-tumor mechanism of *** real-time polymerase chain reaction(qRT-PCR) and Western blot were applied to verify RNA-seq *** reporter assay was performed to examine the transcriptional activity of yes-associated protein(YAP).Results:PZH treatment significantly inhibited the migration,invasion,proliferation and promoted the apoptosis of HCC cells in vitro and in vivo(P<0.01).Transcriptome analysis indicated that Hippo signaling pathway was associated with anti-metastasis function of *** study showed PZH significantly inhibited the expressions of platelet derived growth factor receptor beta(PDGFRB),YAP,connective tissue growth factor(CCN2),N-cadherin,vimentin and matrix metallopeptidase 2(MMP2,P<0.01).Meanwhile,the phosphorylatio

关键词： PienTzeHuang hepatocellular carcinoma RNA-seq Hippo yes-associated protein

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