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Metformin:A promising clinical therapeutical approach for BPH treatment via inhibiting dysregulated steroid hormones-induced prostatic epithelial cells proliferation

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Journal of Pharmaceutical Analysis 2024年第1期14卷 52-68页

作者： tingting yang Jiayu Yuan Yuting Peng Jiale Pang Zhen Qiu Shangxiu Chen Yuhan Huang Zhenzhou Jiang Yilin Fan Junjie Liu Tao Wang Xueyan Zhou Sitong Qian Jinfang Song Yi Xu Qian Lu Xiaoxing Yin Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical UniversityXuzhouJiangsu221004China Department of Pharmacy Affiliated Lianyungang Hospital of Xuzhou Medical UniversityLianyungangJiangsu222061China Department of Pharmacy The Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu221006China New Drug Screening Center Jiangsu Center for Pharmacodynamics Research and EvaluationChina Pharmaceutical UniversityNanjing210009China School of Life Sciences University of EssexEssex CO43SQUnited Kingdom Department of Urology The Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu221006China Department of Pharmacy Affiliated Hospital of Jiangnan UniversityWuxiJiangsu214000China

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.However,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive relationship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met’s anti-proliferative effects were blocked by AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

关键词： Metformin Benign prostatic hyperplasia Sex steroid hormones homeostasis Proliferation DHT YAP1-TEAD4 heterodimer

Clinical characteristics and north-south differences of inflammatory bowel disease in China: A cross-sectional study and meta-analysis

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Frigid Zone Medicine 2024年第1期4卷 23-30页

作者： Qi Liang Bo Qu Chunye Li Yue Hu Chunyi yang tingting yang Yuzhu Di Hui Li Harbin Medical University Harbin 150086China Digestive Department the 2nd Affiliated Hospital of Harbin Medical UniversityHarbin 150086China Huangshi Hospital of Traditional Chinese Medicine Huangshi 435000China

Objective:This study aimed to estimate the incidence rate and clinical characteristics of inflammatory bowel disease(IBD)in the Chinese population,specially comparing the North and South regions.Methods:We designed a questionnaire survey for patients diagnosed with IBD and conducted a systematic literature search in PubMed,China National Knowledge Internet,and Wanfang digital database,covering studies published between 2012 and 2022.Meta-analysis was performed to determine the overall incidence rate and prevalence of clinical manifestations of Crohn's disease(CD)and ulcerative colitis(UC)in China's Mainland.Clinical phenotypes and demographic characteristics were calculated with 95%confidence intervals(CI).A comparison between the northern and southern regions was also conducted.Results:The questionnaire survey included 440 patients,and 64 publications were included for Meta-analysis.The overall incidence rates of IBD,CD,and UC were 1.36(95%CI:0.79-2.33)per 100,000 person-years,0.23(95%CI:0.09-0.58)per 100,000 person-years,and 1.12(95%CI:0.69-1.80)per 100,000 person-years,respectively.The incidence rates of IBD,CD,and UC were all higher in southern China compared to the North.Clinical characteristics of 440 IBD patients from the questionnaire and 2,821 CD patients and 12,809 UC patients from the literature were analyzed.There were more male patients compared to female patients.CD cases in the North exhibited earlier disease diagnosis(P<0.01),more upper gastrointestinal lesions(P<0.01),and higher hospitalizations rates(P<0.01)compared to the South.UC cases in the North had higher severity(P<0.01),anemia rates(P<0.01),and weight loss(P<0.01)compared to the South.Conclusions:The incidence rates of IBD,CD,and UC were higher in southern China than in the North.Northern patients exhibited more severe symptoms compared to their southern counterparts.

关键词： inflammatory bowel disease Crohn's disease ulcerative colitis epidemiology clinical characteristics

Development in oxide metallurgy for improving the weldability of high -strength low-alloy steel-Combined deoxidizers and microalloying elements

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International Journal of Minerals,Metallurgy and Materials 2024年第6期31卷 1263-1284页

作者： tingting Li Jian yang State Key Laboratory of Advanced Special Steel School of Materials Science and EngineeringShanghai UniversityShanghai 200444China

The mechanisms of oxide metallurgy include inducing the formation of intragranular acicular ferrite(IAF)using micron-sized inclusions and restricting the growth of prior austenite grains(PAGs)by nanosized particles during welding.The chaotically oriented IAF and refined PAGs inhibit crack initiation and propagation in the steel,resulting in high impact toughness.This work summarizes the com-bined effect of deoxidizers and alloying elements,with the aim to provide a new perspective for the research and practice related to im-proving the impact toughness of the heat affected zone(HAZ)during the high heat input welding.Ti complex deoxidation with other strong deoxidants,such as Mg,Ca,Zr,and rare earth metals(REMs),can improve the toughness of the heat-affected zone(HAZ)by re-fining PAGs or increasing IAF contents.However,it is difficult to identify the specific phase responsible for IAF nucleation because ef-fective inclusions formed by complex deoxidation are usually multiphase.Increasing alloying elements,such as C,Si,Al,Nb,or Cr,con-tents can impair HAZ toughness.A high C content typically increases the number of coarse carbides and decreases the potency of IAF formation.Si,Cr,or Al addition leads to the formation of undesirable microstructures.Nb reduces the high-temperature stability of the precipitates.Mo,V,and B can enhance HAZ toughness.Mo-containing precipitates present good thermal stability.VN or V(C,N)is ef-fective in promoting IAF nucleation due to its good coherent crystallographic relationship with ferrite.The formation of the B-depleted zone around the inclusion promotes IAF formation.The interactions between alloying elements are complex,and the effect of adding dif-ferent alloying elements remains to be evaluated.In the future,the interactions between various alloying elements and their effects on ox-ide metallurgy,as well as the calculation of the nucleation effects of effective inclusions using first principles calculations will become the focus of oxide metallurgy.

关键词： oxide metallurgy technology heat affected zone high-strength low-alloy steel intragranular acicular ferrite microalloying element

Skin neuropathy and immunomodulation in diseases

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Fundamental Research 2024年第2期4卷 218-225页

作者： Manze Zhang tingting Liu Jing yang Department of Biology Stanford UniversityStanfordCA 94305USA Department of Biochemistry Weill Cornell Medical CollegeNew YorkNY 10065USA IDG/McGovern Institute for Brain Research Center for Life SciencesSchool of Life SciencesPeking UniversityBeijing 100871China Peking University Third Hospital Cancer Center Beijing 100191China

Skin is a vital barrier tissue of the body.Immune responses in the skin must be precisely controlled,which would otherwise cause severe disease conditions such as psoriasis,atopic dermatitis,or pathogenic infection.Research evidence has increasingly demonstrated the essential roles of neural innervations,i.e.,sensory and sympathetic signals,in modulating skin immunity.Notably,neuropathic changes of such neural structures have been observed in skin disease conditions,implicating their direct involvement in various pathological processes.An in-depth understanding of the mechanism underlying skin neuropathy and its immunomodulatory effects could help reveal novel entry points for therapeutic interventions.Here,we summarize the neuroimmune interactions between neuropathic events and skin immunity,highlighting the current knowledge and future perspectives of this emerging research frontier.

关键词： Skin Neuropathy Neuroimmune Psoriasis Atopic dermatitis Pathogenic infection

D-scheduler:A scheduler in time-triggered distributed system through decoupling dependencies between tasks and messages

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Science China(Technological Sciences) 2024年第1期67卷 183-196页

作者： yang tingting ZHANG YuQi YUE FengLai WUNIRI QiQiGe TONG Chao School of Computer Science&Engineering Beihang UniversityBeijing 100191China State Key Laboratory of Virtual Reality Technology and Systems Beihang UniversityBeijing 100191China National Innovation Center of Intelligent and Connected Vehicles Beijing 100176China

Time-triggered architecture,as a mainstream design of the distributed real-time system,has been successfully applied in the aerospace,automotive and mechanical industries.However,time-triggered scheduling is a challenging NP-hard problem.There are few studies that could quickly solve the scheduling problem of large distributed time-triggered systems.To solve this problem,a communication affinity parameter is defined in this paper to describe the degree of bias of the shaper task towards sending or receiving messages.Based on this,an innovative task-message decoupling model named D-scheduler is built to reduce the computation complexity of the scheduling problem in large-scale systems.Additionally,we provide mathematical proof that our model is a convex optimization that is easy to solve with existing computational tools.Our experiments substantiate the efficacy of the D-scheduler.It dramatically reduces the scheduling complexity of large-scale real-time systems with a small loss of solving space compared to the federal scheduler.

关键词： time-triggered architecture time-triggered scheduling communication affinity parameter task-message decoupling model

Perfluorinated iodine alkanes promote the differentiation of mouse embryonic stem cells by regulating estrogen receptor signaling

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Journal of Environmental Sciences 2024年第3期137卷 443-454页

作者： Zhihua Ren Xiaoxi yang tingting Ku Qian S.Liu Jiefeng Liang Qunfang Zhou Francesco Faiola Guibin Jiang State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China College of Resources and Environment University of Chinese Academy of SciencesBeijing 100049China College of Environment and Resource Research Center of Environment and HealthShanxi UniversityTaiyuan 030006China College of Sino-Danish University of Chinese Academy of SciencesBeijing 100049China

Investigating the development toxicity of perfuorinated iodine alkanes(PFIs)is critical,given their estrogenic effects through binding with estrogen receptors(ERs).In the present study,two PFIs,including dodecafuoro-1,6-diiodohexane(PFHx DI)and tridecafuorohexyl iodide(PFHx I),with binding preference to ERαand ERβ,respectively,were selected to evaluate their effects on proliferation and differentiation of the mouse embryonic stem cells(m ESCs).The results revealed that,similar to E_(2),50μmol/L PFHx DI accelerated the cell proliferation of the m ESCs.The PFI stimulation at the exposure concentrations of 2–50μmol/L promoted the differentiation of the m ESCs as characterized by the upregulation of differentiation-related biomarkers(i.e.,Otx2 and Dnmt3β)and downregulation of pluripotency genes(i.e.,Oct4,Nanog,Sox2,Prdm14 and Rex1).Comparatively,PFHx DI exhibited higher induction effect on the differentiation of the m ESCs than did PFHx I.The tests on ER signaling indicated that both PFI compounds induced exposure concentration-dependent expressions of ER signaling-related biomarkers(i.e.,ERα,ERβand Caveolin-1)in the m ESCs,and the downstream ER responsive genes(i.e.,c-fos,c-myc and c-jun)well responded to PFHx I stimulation.The role of ER in PFI-induced effects on the m ESCs was further validated by the antagonistic experiments using an ER inhibitor(ICI).The findings demonstrated that PFIs triggered ER signaling,and perturbed the differentiation program of the m ESCs,causing the potential health risk during early stage of development.

关键词： Perfuorinated iodine alkanes(PFIs) Embryonic stem cells(ESCs) Developmental toxicity Cell differentiation Estrogen receptor-related signaling

Effectiveness and safety of acupuncture in treatment of pregnancyrelated symptoms:a systematic review and Meta-analysis

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Journal of Traditional Chinese Medicine 2024年第1期44卷 16-26页

作者： LIU tingting LIU Tongou LIU Mingfu School of Traditional Chinese Medicine Clinical Medicine Hubei University of Traditional Chinese MedicineWuhan 430000China First Clinical College of Hubei University of Traditional Chinese Medicine Wuhan 430000China Department of Acupuncture and Tuina Affiliated Hospital of Hubei University of Traditional Chinese MedicineHubei Provincial Hospital of Traditional Chinese MedicineWuhan 430000China

OBJECTIVE:To systematically evaluate the efficacy and safety of acupuncture(AM)in the treatment of pregnancyrelated symptoms such as acute vomiting during pregnancy.METHODS:We comprehensively searched the available literature up to November 2021,including Pub Med,Embase,Cochrane Library,Chinese Biomedical Literature Database,and China National Knowledge Infrastructure Database,for randomized controlled trials(RCTs)on AM for the treatment of severe vomiting,insomnia,pharyngeal and pelvic pain,mood abnormalities,and dyspepsia during pregnancy.RESULTS:Sixteen RCTs with a cumulative sample size of 1178 cases were included.Of these,964 patients were included in the Meta-analysis.The Meta-analysis results showed that AM was more efficient than Western medicine in treating discomfort during pregnancy[odds ratio(OR)=1.19,95%confidence interval(CI)(1.11,1.28),P<0.01].AM was better than the control group in improving the visual analog scale scores[standard mean difference(SMD)=0.62,95%CI(0.53,0.71),P<0.01].AM was superior to the control group in improving Numerical Rating Scale(NRS)symptom scores[OR=7.31,95%CI(3.36,15.94),P<0.01].There was no significant difference in adverse effects between the AM and sham-AM groups and the analgesic drug group[OR=0.70,95%CI(0.39,1.28),P=0.25],but the treatment and control groups had mild adverse effects with a low incidence.CONCLUSIONS:AM is more effective than other treatments or pharmacotherapy alone in the treatment of pregnancy-related symptoms,and is relatively safe.However,the quality of the included trials was rather poor,and high-quality studies are required to confirm our findings.

关键词： acupuncture pregnancy nausea vomiting sleep initiation and maintenance disorders low back pain pelvic pain mood abnormalities Meta-analysis systematic review

Potassium and calcium channels in different nerve cells act as therapeutic targets in neurological disorders

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Neural Regeneration Research 2025年第5期20卷 1258-1276页

作者： Qing Qiu Mengting yang Danfeng Gong Haiying Liang tingting Chen Department of Pharmacology School of PharmacyNantong UniversityNantongJiangsu ProvinceChina Jiangsu Province Key Laboratory of Inflammation and Molecular Drug Target NantongJiangsu ProvinceChina Department of Pharmacy Longyan First Affiliated Hospital of Fujian Medical UniversityLongyanFujian ProvinceChina

The central nervous system, information integration center of the body, is mainly composed of neurons and glial cells. The neuron is one of the most basic and important structural and functional units of the central nervous system, with sensory stimulation and excitation conduction functions. Astrocytes and microglia belong to the glial cell family, which is the main source of cytokines and represents the main defense system of the central nervous system. Nerve cells undergo neurotransmission or gliotransmission, which regulates neuronal activity via the ion channels, receptors, or transporters expressed on nerve cell membranes. Ion channels, composed of large transmembrane proteins, play crucial roles in maintaining nerve cell homeostasis. These channels are also important for control of the membrane potential and in the secretion of neurotransmitters. A variety of cellular functions and life activities, including functional regulation of the central nervous system, the generation and conduction of nerve excitation, the occurrence of receptor potential, heart pulsation, smooth muscle peristalsis, skeletal muscle contraction, and hormone secretion, are closely related to ion channels associated with passive transmembrane transport. Two types of ion channels in the central nervous system, potassium channels and calcium channels, are closely related to various neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy. Accordingly, various drugs that can affect these ion channels have been explored deeply to provide new directions for the treatment of these neurological disorders. In this review, we focus on the functions of potassium and calcium ion channels in different nerve cells and their involvement in neurological disorders such as Parkinson's disease, Alzheimer's disease, depression, epilepsy, autism, and rare disorders. We also describe several clinical drugs that target potassium or calcium channels in nerve cells and could be used to treat these disorders. We concluded that

关键词： astrocytes calcium channels central nervous system extracellular ion concentration microglia neurological disorders neurons potassium channels

Molecular design for enhanced spin transport in molecular semiconductors

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Nano Research 2023年第12期16卷 13457-13473页

作者： tingting yang yang Qin Xianrong Gu Xiangnan Sun Key Laboratory of Nanosystem and Hierarchical Fabrication CAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijing 100190China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing 100049China School of Material Science and Engineering Zhengzhou UniversityZhengzhou 450001China

Molecular semiconductors(MSCs),characterized by a longer spin lifetime than most of other materials due to their weak spin relaxation mechanisms,especially at room temperature,together with their abundant chemical tailorability and flexibility,are regarded as promising candidates for spintronic applications.Molecular spintronics,as an emerging subject that utilizes the unique properties of MSCs to study spin-dependent phenomena and properties,has attracted wide attention.In molecular spintronic devices,MSCs play the role as medium for information transport,process,and storage,in which the efficient spin inject–transport process is the prerequisite.Herein,we focus mainly on summarizing and discussing the recent advances in theoretical principles towards spin transport of MSCs in terms of the injection of spin-polarized carriers through the ferromagnetic metal/MSC interface and the subsequent transport within the MSC layer.Based on the theoretical progress,we cautiously present targeted design strategies of MSCs that contribute to the optimization of spin-transport efficiency and give favorable approaches to exploring accessional possibilities of spintronic materials.Finally,challenges and prospects regarding current spin transport are also presented,aiming to promote the development and application of the rosy and energetic field of molecular spintronics.

关键词： molecular spintronics molecular semiconductors spin transport spin injection molecular design