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MPDZ variants associated with epilepsies and/or febrile seizures and the individualized genotype-phenotype correlation

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Genes & Diseases 2024年第4期11卷 124-127页

作者： Junxia Luo yun li Yong Lv Xin li Bing qin Chuanfang Cheng Xiaorong liu Weiping liao jie wang Zaifen Gao Department of Epilepsy Center Children's Hospital Affiliated to Shandong UniversityJinanShandong 250022China Department of Epilepsy Center Jinan Children's HospitalJinanShandong 250022China Department of Brain Function and Neuroelectrophysiology The Affiliated Nanhua HospitalHengyang Medical SchoolUniversity of South ChinaHengyangHunan 421001China Department of Pediatrics The First Affiliated Hospital of University of Science and Technology of China(Anhui Provincial Hospital)HefeiAnhui 230001China Department of Pediatrics The Second HospitalCheeloo College of MedicineShandong UniversityJinanShandong 250033China Epilepsy Center and Department of Neurosurgery The First Affliated Hospital of Jinan UniversityGuangzhouGuangdong 510630China Department of Cardiology The Second Afiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong 510260China Institute of Neuroscience and Department of Neurology of the Second affiliated hospital of Guangzhou Medical {2. GuangzhouGuangdong 510260China Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of china GuangzhouGuangdong 510260China

The multiple PDZ domain crumbs cell polarity complex component gene(MPDZ;MIM:603785),is highly expressed in the brain across the whole *** encodes the multiple PDZ domain protein,which is a member of the NMDAR signaling complex that may play a role in the control of AMPAR potentiation and synaptic plasticity in excitatory synapses."Previously,MPDZ variants have been demonstrated to be associated with autosomal recessive congenital hydrocephalus-2.HYC2.MIM:6152.9)which is commonly complicated by brain abnormalities and developmental *** were reported in only one *** association between MPDz and epilepsy requires clarification.

关键词： epilepsy febrile congenital

RPRD1B/CREPT facilitates the progression of diffuse large B-cell lymphoma by inhibiting apoptosis through the NF-κB signaling pathway

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Asian Pacific Journal of Tropical Biomedicine 2024年第7期14卷 307-318页

作者： Lu Xu Zhi-hao Xie Jun li Shi Tao Fang-li Ren Yin-Yin wang Zhi-{4.e Chang Xin-Bao hao Department of Hematology The First Affiliated Hospital of Hainan Medical UniversityHaikou570102China State Key Laboratory of Membrane Biology School of MedicineTsinghua UniversityBeijing 100084China Heya Beijing Med-Biotech Inc. Beijing 100084China Department of Hematology Roswell Park Comprehensive Cancer CenterNY 14263USA

Objective:To investigate the role of RPRD1B in the progression of diffuse large B-cell lymphoma(DLBCL)and its potential as a therapeutic ***:This study analyzed RPRD1B expression in DLBCL and normal tissues using public databases and assessed its prognostic impact through survival *** vitro and in vivo experiments were conducted to explore the mechanisms by which RPRD1B influences tumor growth and ***:RPRD1B expression was significantly elevated in DLBCL compared to normal tissues and was associated with poor *** vitro and in vivo experiments demonstrated that RPRD1B promoted lymphoma cell proliferation and inhibited apoptosis through the NF-κB signaling ***:RPRD1B plays a critical role in the progression of DLBCL by modulating apoptosis and cellular *** RPRD1B may offer a novel therapeutic strategy for DLBCL,suggesting its potential as a prognostic marker and therapeutic target in hematological malignancies.

关键词： RPRD1B RNAPⅡ Diffuse large B-cell lymphoma NF-κB Apoptosis

Early detection of multiple endocrine neoplasia type 1: A case report

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World Journal of Gastroenterology 2024年第26期30卷 3247-3252页

作者： jie-hao Yuan Su Luo Ding-Guo Zhang {2.-Sheng wang Department of Gastroenterology Shenzhen People’s Hospital(The Second Clinical Medical CollegeJinan University)Shenzhen 518020Guangdong ProvinceChina

BACKGROUND Multiple endocrine neoplasias(MENs)are a group of hereditary diseases invol-ving multiple endocrine glands,and their prevalence is *** type 1(MEN1)has diverse clinical manifestations,mainly involving the parathyroid glands,gastrointestinal tract,pancreas and pituitary gland,making it easy to miss the clinical *** SUMMARY We present the case of a patient in whom MEN1 was detected early.A middle-aged male with recurrent abdominal pain and diarrhea was admitted to the *** tests at admission revealed hypercalcemia and hypophosphatemia,and emission computed tomography of the parathyroid glands revealed a hy-perfunctioning parathyroid *** findings suggested a duodenal bulge and *** endoscopy revealed a hypoechoic lesion in the duodenal *** blood tests revealed elevated levels of serum *** was performed,and pathological analysis of the surgical specimens revealed a parathyroid adenoma after parathyroidectomy and a neuroendocrine tumor after duodenal *** time from onset to the definitive diagnosis of MEN1 was only approximately 1 *** For patients who present with gastrointestinal symptoms accompanied by hyper-calcemia and hypophosphatemia,clinicians need to be alert to the possibility of MEN1.

关键词： Multiple endocrine neoplasia type 1 Gastrointestinal symptoms Hypercal-cemia Early detection Case report

Biomimetic design of highly flexible metal oxide nanofibrous membranes with exceptional mechanical performance for superior phosphopeptide enrichment

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Nano Research 2024年第5期17卷 4270-4278页

作者： Xue Mao Zhen-Zhen li Dong-lian {2. Wei-Dong Han Gao-Peng li Yao-Yu {4. Kun Zhang School of Textile Science and Engineering Key Laboratory of Functional Textile Material and Product(Ministry of Education)Xi’an Polytechnic UniversityXi’an 710048China Key Laboratory of Magnetic Molecules&Magnetic Information Materials of the Ministry of Education School of Chemistry&Material ScienceShanxi Normal UniversityTaiyuan 030031China Department of Clinical Laboratory The Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710004China Shanghai iProteome Biotechnology Co. LtdShanghai 201210China College of Chemistry&Materials Science Northwest UniversityXi'an 710127China

Developing free-standing and mechanical robust membrane materials capable of superior enrichment of phosphopeptides for analyzing and identifying the specific phosphoproteome of cancer cells is significant in understanding the molecular mechanisms of cancer development and exploring new therapeutic approaches,but still a significant challenge in materials *** this end,we firstly constructed highly flexible ZrTiO_(4. nanofibrous membranes(NFMs)with excellent mechanical stabi{2.ty through a cost-effective and scalable electrospinning and subsequent calcination ***,to further increase the enrichment capacity of the phosphopeptide,the biomimetic TiO_(2.@ZrTiO_(4. NFMs with root hair or leaf {2.ke branch microstructure are developed by the hydrothermal post-synthetic modification of ZrTiO_(4. NFMs through growing unfur{2.ng TiO_(2. nanosheets onto the ZrTiO_(4. ***,remarkable flexibi{2.ty and mechanical stabi{2.ty enable the resulting TiO_(2.@ZrTiO_(4. NFMs excellent practicabi{2.ty,while the biomimetic microstructure allows it outstanding enrichment abi{2.ty of the phosphopeptide and identification abi{2.ty of the specific phosphoproteins in the digest of cervical cancer ***,6770 phosphopeptides can be enriched by TiO_(2.@ZrTiO_(4. NFMs(2.05 corresponding phosphoproteins can be identified),and the value is much higher than that of ZrTiO_(4. NFMs(6399 phosphopeptides and 2.32.identified phosphoproteins)and commercial high-performance TiO_(2. particles(4.2. phosphopeptides and 1811 identified phosphoproteins).These results demonstrate the super abi{2.ty of TiO_(2.@ZrTiO_(4. NFMs in phosphopeptide enrichment and great potential for exploring the pathogenesis of cancer.

关键词： inorganic nanofibers flexible ceramic nanofibrous membranes biomimetic materials exceptional mechanical performance flexibility

Genistein stimulates osteoblastic differentiation via p38 MAPK-Cbfa1 pathway in bone marrow culture

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Acta Pharmacologica Sinica 2007年第10期28卷 1597-1602页

作者： qing-chuan liAO~2.Zhou-sheng XIAO~({2.5),Yan-fang qin~3,Hong-hao ZHOU~{2.2.{{2. Children's hospital,Nanjing Medical university,Nanjing 2.0008,china,~3 Department of Pathology,School of Medicine,{12.university,Guangzhou 510632.china ~{2.Institute of Clinical Pharmacology,Central South university,Changsha {2.0078,china ated Childrenos hospital Nanjing Medical University Nanjing 210008 China. xiaozs64@***.

Aim:To test the hypothesis that genistein stimulates the osteoblastic differentia-tion through the p38 mitogen activated protein kinase (MAPK)-core-binding fac-tor 1 (Cbfa1) ***:The activation of p38 MAPK was detected byWestern *** phosphatase (ALP) activity and calcium depositionwere assessed for osteoblastic differentiation of bone marrow-derived mesenchy-mal stem cell (BMSC) *** expression of Cbfa1 was analyzed at both themRNA and protein *** activity of Cbfa1 was detected by electrophoreticmobility shift *** sialoprotein (BSP),ALP,osteocalcin (OC),andosteopontin (OPN) gene transcription were also evaluated by either RT-PCR orNorthern ***:Genistein (0.01-1 μmol/L) dose dependently led tothe rapid and sustained activation of the p38 MAPK pathway in mouse *** with genistein (1 μmol/L) resulted in increased ALP activityand calcium deposition of BMSC cultures as a function of *** alsoenhanced Cbfa1 DNA binding activity and promoted the expressions of Cbfa1itself as well as several Cbfa1-regulated genes,including ALP,BSP,OC,and *** treatment with p38 MAPK inhibitor (SB2.3580) diminished thegenistein-induced osteoblastic maturation and p38 MAPK-Cbfa1 activation inmouse BMSC ***:These results indicated that genistein couldstimulate the osteoblastic differentiation of BMSC cultures through the p38MAPK-Cbfa1 pathway.

关键词： bone marrow-derived mesenchymal stem cells core-binding factor 1 osteoblastic differentiation genistein mitogen-activated protein kinase

Unveiling the role of hypoxia-inducible factor 2.lpha in osteoporosis:Implications for bone health

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World Journal of Stem Cells 2024年第4期16卷 389-409页

作者： ling-ling {2. Zhan-jin Lu Shun-Kui Luo {4. li Zhe Yang Hong-{4. Lu Department of Gerontology The Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhai 519000Guangdong ProvinceChina Department of Endocrinology and Metabolism The Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhai 519000Guangdong ProvinceChina Guangdong Provincial Key Laboratory of Biomedical Imaging The Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhai 519000Guangdong ProvinceChina Department of Endocrinology and Metabolism Zhuhai People’s Hospital(Zhuhai Clinical Medical College of Jinan Universitythe First Hospital Affiliated with Medical College of Macao University of Science and Technology)Zhuhai 519000Guangdong ProvinceChina

BACKGROUND Osteoporosis(OP)has become a major public health problem *** OP treatments are based on the inhibition of bone resorption,and it is necessary to identify additional treatments aimed at enhancing *** the bone marrow(BM)niche,bone mesenchymal stem cells(BMSCs)are exposed to a hypoxic ***,a few studies have demonstrated that hypoxiainducible factor 2.lpha(HIF-2.)is involved in BMSC osteogenic differentiation,but the molecular mechanism involved has not been *** To investigate the effect of HIF-2.on the osteogenic and adipogenic differentiation of BMSCs and the hematopoietic function of hematopoietic stem cells(HSCs)in the BM niche on the progression of *** Mice with BMSC-specific HIF-2.knockout(Prx1-Cre;Hif-2.fl/fl mice)were used for in vivo *** quantification was performed on mice of two genotypes with three interventions:Bilateral ovariectomy,semilethal irradiation,and dexamethasone ***,the hematopoietic function of HSCs in the BM niche was compared between the two mouse *** vitro,the HIF-2.agonist roxadustat and the HIF-2.inhibitor PT2.99 were used to investigate the function of HIF-2.in BMSC osteogenic and adipogenic ***,we investigated the effect of HIF-2.on BMSCs via treatment with the mechanistic target of rapamycin(mTOR)agonist MHY14.5 and the mTOR inhibitor *** The quantitative index determined by microcomputed tomography indicated that the femoral bone density of Prx1-Cre;Hif-2.fl/fl mice was lower than that of Hif-2.fl/fl mice under the three intervention *** vitro,Hif-2.fl/fl mouse BMSCs were cultured and treated with the HIF-2.agonist roxadustat,and after 7 d of BMSC adipogenic differentiation,the oil red O staining intensity and mRNA expression levels of adipogenesis-related genes in BMSCs treated with roxadustat were decreased;in addition,after 14.d of osteogenic differentiation,BMSCs treated with roxadusta

关键词： Hypoxia-inducible factor-2. Bone marrow niche Bone mesenchymal stem cells Osteoporosis Osteogenic/adipogenic differentiation Mechanistic target of rapamycin signaling pathway

Effectiveness of cardioneuroablation in different subtypes of vasovagal syncope

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Journal of Geriatric Cardiology 2024年第6期21卷 651-657页

作者： Bin TU Zi-hao LAI Ai-Yue CHEN Zhi-Yuan WENG Si-Min cai Zhu-Xin ZHANG {2.-Kun ZHOU {2.-Hui ZHENG Yan YAO Arrhythmia Center Fuwai HospitalNational Center for Cardiovascular DiseasesNational Key LaboratoryChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Cardiac Center Beijing Chaoyang HospitalCapital Medical UniversityBeijingChina Cardiovascular Department The First Affiliated HospitalFujian Medical UniversityFujian Institute of HypertensionFujianChina Department of Cardiovascular The Second Affiliated Hospital of Zhejiang University School of MedicineZhejiangChina

BACKGROUND Cardioneuroablation(CNA)has shown encouraging results in patients with vasovagal syncope(VVS).However,data on different subtypes was *** This observational study retrospectively enrolled 14. patients[mean age:4.±18 {2.ars,51 males(36.2.)]with the diagnosis of *** characteristics among different types of VVS and the outcomes after CNA were *** After a mean follow-up of 4.3±1.5 {2.ars,4. patients(2..1%)experienced syncope/pre-syncope events after ***/pre-syncope recurrence significantly differed in each subtype(P=0.04..The cardioinhibitory type of VVS had the lowest recurrence rate after the procedure(n=6,16.7%),followed by mixed(n=2.,30.6%)and vasodepressive(n=9,4..0%).Additionally,a significant difference was observed in the analyses of the Kaplan-Meier survival curve(P=0.02..Syncope/pre-syncope burden was significantly reduced after CNA in the vasodepressive type(Pline deceleration capacity(DC)level than those without(7.4.1.0 ms vs.9.0±1.6 ms,P=0.01).Patients with DC4.ms had an 8.1(HR=8.1,95%CI:2.2.30.0,P=0.02.times risk of syncope/pre-syncope recurrence after CNA compared to patients with DC≥8.4.ms,and this association still existed after adjusting for age and sex(HR=8.1,95%CI:2.2.30.1,P=0.02..CONCLUSIONS Different subtypes exhibit different event-free *** vasodepressive type exhibited the lowest event-free rate,but those patients with DC≥8.4.ms might benefit from CNA.

关键词： syncope subtypes diagnosis

Mitochondrial dysfunction:mechanisms and advances in therapy

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2362-2390页

作者： Yao Zong hao li Peng liao long Chen Yao {4. Yongqiang Zheng Changqing Zhang Delin liu Minghao Zheng Junjie Gao Centre for Orthopaedic Research Medical SchoolThe University of Western AustraliaNedlandsWA 6009Australia Department of Orthopaedics Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200233China Institute of Microsurgery on Extremities and Department of Orthopedic SurgeryShanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200233China State Key Laboratory of Cell Biology Shanghai Institute of Biochemistry and Cell BiologyCAS Center for Excellence in Molecular Cell ScienceChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China Sixth People’s hospital Fujian No.16Luoshan SectionJinguang RoadLuoshan StreetJinjiang CityQuanzhouFujianChina

Mitochondria,with their intricate networks of functions and information processing,are pivotal in both health regulation and disease ***,mitochondrial dysfunctions are identified in many common pathologies,including cardiovascular diseases,neurodegeneration,metabolic syndrome,and ***,the multifaceted nature and elusive phenotypic threshold of mitochondrial dysfunction complicate our understanding of their contributions to ***,these complexities do not prevent mitochondria from being among the most important therapeutic *** recent {2.ars,strategies targeting mitochondrial dysfunction have continuously emerged and transitioned to clinical *** intervention such as using healthy mitochondria to replenish or replace damaged mitochondria,has shown promise in preclinical trials of various *** components,including mtDNA,mitochondria-located microRNA,and associated proteins can be potential therapeutic agents to augment mitochondrial function in immunometabolic diseases and tissue ***,we review current knowledge of mitochondrial pathophysiology in concrete examples of common *** also summarize current strategies to treat mitochondrial dysfunction from the perspective of dietary supplements and targeted therapies,as well as the clinical translational situation of related pharmacology ***,this review discusses the innovations and potential applications of mitochondrial transplantation as an advanced and promising treatment.

关键词： dysfunction injuries replace

Anti-atherosclerotic effects and molecular targets of ginkgolide B from Ginkgo biloba

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Acta Pharmaceutica Sinica B 2024年第1期14卷 1-19页

作者： Weile ye jiaojiao wang Peter J{4.ttle jiami Zou Zhihua Zheng jing Lu Yanjun Yin hao {4.u Dongmei Zhang Peiqing {4.u Suowen Xu Wencai ye Zhiping {4.u International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education(MOE)of china Jinan UniversityGuangzhou 510632China Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research College of PharmacyJinan UniversityGuangzhou 510632China State Key Laboratory of Bioactive Molecules and Druggability Assessment Jinan UniversityGuangzhou 510632China Pharmacy Australia Centre of Excellence School of PharmacyUniversity of QueenslandWoolloongabba QLD 4102Australia Sunshine Coast Health Institute and School of Health and Behavioural Sciences University of the Sunshine CoastBirtinya QLD 4575Australia National-Local Joint Engineering Lab of Druggability and New Drugs Evaluation Guangdong Provincial Key Laboratory of New Drug Design and EvaluationSun Yat-sen UniversityGuangzhou 510006China School of Pharmacy Bengbu Medical CollegeBengbu 233030China Institute of Endocrine and Metabolic Diseases the First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230026China

Bioactive compounds derived from herbal medicinal plants modulate various therapeutic targets and signaling pathways associated with cardiovascular diseases(CVDs),the world’s primary cause of *** biloba,a well-known traditional Chinese medicine with notable cardiovascular actions,has been used as a cardio-and cerebrovascular therapeutic drug and nutraceutical in Asian countries for *** studies have shown that ginkgolide B,a bioactive component in Ginkgo biloba,can ameliorate atherosclerosis in cultured vascular cells and disease *** clinical relevance,several clinical trials are ongoing or being completed to examine the efficacy and safety of ginkgolide B-related drug preparations in the prevention of cerebrovascular diseases,such as ischemia ***,we present a comprehensive review of the pharmacological activities,pharmacokinetic characteristics,and mechanisms of action of ginkgolide B in atherosclerosis prevention and *** highlight new molecular targets of ginkgolide B,including nicotinamide adenine dinucleotide phosphate oxidases(NADPH oxidase),lectin-like oxidized LDL receptor-1(LOX-1),sirtuin 1(SIRT1),platelet-activating factor(PAF),proprotein convertase subtilisin/kexin type 9(PCSK9)and ***,we provide an overview and discussion of the therapeutic potential of ginkgolide B and highlight the future perspective of developing ginkgolide B as an effective therapeutic agent for treating atherosclerosis.

关键词： Cardiovascular disease Atherosclerosis Ginkgo biloba Ginkgolide B Endothelial dysfunction LOX-1 PCSK9 PAF-R antagonist