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Ivermectin as an adjunct treatment for hospitalized adult COVID-19 patients: A randomized multi-center clinical trial

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Asian Pacific Journal of Tropical Medicine 2021年第6期14卷 266-273页

作者： Morteza Shakhsi Niaee Peyman Namdar Abbas Allami Leila Zolghadr Amir Javadi Amin Karampour Mehran Varnaseri Behzad Bijani Fatemeh Cheraghi Yazdan Naderi Fatemeh Amini Masoumeh Karamyan Mohammad Jafar YadYad Ramin Jamshidian Nematollah Gheibi Sciences and Technology Park QazvinIran Department of Surgery Qazvin University of Medical SciencesQazvinIran Department of Infectious Diseases Clinical Research Development UnitBouAliSina HospitalQazvin University of Medical SciencesQazvinIran Department of Chemistry Imam Khomeini International University QazvinIran Department of Social Sciences School of Medicine Qazvin University of Medical SciencesQazvinIran Infectious and Tropical Diseases Research center Ahvaz Jundishapur University of Medical SciencesAhvazIran Department of Infectious Diseases Qazvin University of Medical SciencesQazvinIran Cellular and Molecular Research center Research Institute for Prevention of Non-Communicable DiseasesQazvin University of Medical SciencesQazvinIran Department of Persian Medicine School of MedicineShiraz University of Medical SciencesShirazIran

Objective: To evaluate different doses of ivermectin in adult patients with mild COVID-19 and to evaluate the effect of ivermectin on mortality and clinical ***: A randomized, double-blind, placebo-controlled, multicenter clinical trial was performed at five hospitals. A total of 180 mild hospitalized patients with COVID-19 confirmed by PCR or chest image tests were enrolled and allocated to six arms including hydroxychloroquine 200 mg twice per day, placebo plus hydroxychloroquine 200 mg twice per day, single dose ivermectin(200 μg/kg), three low interval doses of ivermectin(200, 200, 200 μg/kg), single dose ivermectin(400 μg/kg), and three high interval doses of ivermectin(400, 200, 200 μg/kg). The primary endpoint of this trial was all-cause of mortality or clinical recovery. The radiographic findings, hospitalization and low O_2 saturation duration, and hematological variables of blood samples were analyzed. Results: A total of 16.7%(5/30) and 20.0%(6/30) patients died in arms treated with hydroxychloroquine 200 mg twice per day and placebo plus hydroxychloroquine 200 mg twice per day, respectively, and a reduction in mortality rate in patients receiving ivermectin treatment to 0%, 10%, 0% and 3.3% for arms 1-4 were observed. Risk of mortality was also decreased about 15% in the ivermectin treated arms. Conclusions: Ivermectin as an adjunct reduces the rate of mortality, time of low O_2 saturation, and duration of hospitalization in adult COVID-19 patients. The improvement of other clinical parametersshows that ivermectin, with a wide margin of safety, had a high therapeutic effect on COVID-19.

关键词： SARS-COV-2 Ivermectin Randomized controlled trial Dose-respond relationship

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Efficacy of Huadananshen mistura on insomnia: a randomized, double-blind, placebo-controlled, and multi-center clinical trial

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Journal of Traditional Chinese Medicine 2013年第4期33卷 423-427页

作者： Huafang Li Xiaoli Yan Ting Li Jian Xu Qiaochu Wang Yifeng Xu Department of Psychiatry Shanghai Mental Health Center Shanghai Jiao Tong University School of Medicine Department of Insomnia Shanghai Chinese Medicine Hospital

OBJECTIVE: To evaluate the effect of Huadananshen mistura in clinical treatment of Chinese patients with insomnia. METHODS: In this randomized, double-blind, placebo-controlled, multi-center study, 244 patients with insomnia were randomly assigned to a placebo group, a low-dose (10 mL/day), or a high-dose (20 mL/day) mistura group. Efficacy was assessed by using the sleep dysfunction rating scale (SDRS) and clinical Global Impression-Improvement (CGI-I) scores. Safety and tolerability assessments included emergent adverse events, laboratory tests, and electrocardiograms. RESULTS: Total SDRS scores decreased in all three groups, and there were significant differences between the placebo group and the lowand high-dose mistura groups (P=0.000). CGI-I ratings in the lowand high-dose mistura groups were sig-nificantly better than that of the placebo group (P= 0.000). Incidences of rebound insomnia were similar in all three groups (placebo group: 6.94% , low-dose mistura group: 12.99% , and high-dose mistura group: 10.96% ; P=0.475). The efficacy of Huadananshen mistura in the lowor high-dose group was significantly better than that of the placebo group (P=0.000), but with no significant difference found between the lowand high-dose mistura groups (P=0.887). The rates of adverse events were similar in the three groups (placebo 2.44% , low-dose mistura 0%, and high-dose mistura 5%; P=0.088). CONCLUSION: Huadananshen mistura is an effective and generally well-tolerated hypnotic medicine for the treatment of Chinese patients with insomnia.

关键词： Sleep initiation and maintenance disorders Medicine Chinese traditional Randomized controlled trials Double-blind method Huadananshen mistura

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Interaction of major facilitator superfamily domain containing 2A with the blood-brain barrier

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Neural Regeneration Research 2025年第8期20卷 2133-2152页

作者： Yilun Ma Taiwei Dong Fei Luan Juanjuan Yang Feng Miao Peifeng Wei College of Pharmacy and First clinical Medical College Shaanxi University of Chinese MedicineXianyangShaanxi ProvinceChina National Drug clinical trial Agency The Second Affiliated Hospital of Shaanxi University of Chinese Medicine/Xixian New District Central HospitalXi′anShaanxi ProvinceChina

The functional and structural integrity of the blood-brain barrier is crucial in maintaining homeostasis in the brain microenvironment;however,the molecular mechanisms underlying the formation and function of the blood-brain barrier remain poorly *** major facilitator superfamily domain containing 2A has been identified as a key regulator of blood-brain barrier *** plays a critical role in promoting and maintaining the formation and functional stability of the blood-brain barrier,in addition to the transport of lipids,such as docosahexaenoic acid,across the blood-brain ***,an increasing number of studies have suggested that major facilitator superfamily domain containing 2A is involved in the molecular mechanisms of blood-brain barrier dysfunction in a variety of neurological diseases;however,little is known regarding the mechanisms by which major facilitator superfamily domain containing 2A affects the blood-brain *** paper provides a comprehensive and systematic review of the close relationship between major facilitator superfamily domain containing 2A proteins and the blood-brain barrier,including their basic structures and functions,cross-linking between major facilitator superfamily domain containing 2A and the blood-brain barrier,and the in-depth studies on lipid transport and the regulation of blood-brain barrier *** comprehensive systematic review contributes to an in-depth understanding of the important role of major facilitator superfamily domain containing 2A proteins in maintaining the structure and function of the blood-brain barrier and the research progress to *** will not only help to elucidate the pathogenesis of neurological diseases,improve the accuracy of laboratory diagnosis,and optimize clinical treatment strategies,but it may also play an important role in prognostic *** addition,the effects of major facilitator superfamily domain containing 2A on blood-brain barrier lea

关键词： blood-brain barrier(BBB) caveolin-1 central nervous system docosahexaenoic acid endothelial cells lysophosphatidylcholine major facilitator superfamily domain containing 2A(MFSD2A) transcytosis

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Lipid droplets in the nervous system:involvement in cell metabolic homeostasis

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Neural Regeneration Research 2025年第3期20卷 740-750页

作者： Yuchen Zhang Yiqing Chen Cheng Zhuang Jingxuan Qi Robert Chunhua Zhao Jiao Wang School of Life Sciences Shanghai UniversityShanghaiChina School of Medicine Shanghai UniversityShanghaiChina Institute of Basic Medical Sciences Chinese Academy of Medical Sciences School of Basic MedicinePeking Union Medical CollegeBeijingChina center of Excellence in Tissue Engineering Chinese Academy of Medical SciencesBeijingChina Beijing Key Laboratory of New Drug Development and clinical trial of Stem Cell Therapy BeijingChina

Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous *** droplet formation begins with the synthesis of neutral lipids in the endoplasmic ***,lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis;however,recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous *** addition to their role in regulating cell metabolism,lipid droplets play a protective role in various cellular stress ***,lipid droplets exhibit specific functions in neurons and glial *** of lipid droplet formation leads to cellular dysfunction,metabolic abnormalities,and nervous system *** review aims to provide an overview of the role of lipid droplets in the nervous system,covering topics such as biogenesis,cellular specificity,and ***,it will explore the association between lipid droplets and neurodegenerative *** the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.

关键词： Alzheimer's disease lipid droplet biogenesis lipid droplets lipid metabolism nervous system neurodegenerative disorders oxidative stress Parkinson's disease

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Antithetical impacts of deleterious LRP1B mutations in non-squamous and squamous NSCLCs on predicting benefits from immune checkpoint inhibitor alone or with chemotherapy over chemotherapy alone: retrospective analyses of the POPLAR/OAK and CHOICE-01 trial

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Science China Life Sciences 2025年第1期 249-262页

作者： Jinliang Wang Wenyong Zhou Yu Xu Jianchun Duan Qiaoxia Zhou Guoqiang Wang Leo Li Chunwei Xu Wenxian Wang Shangli Cai Zhijie Wang Jie Wang Department of Oncology The Fifth Medical Center of Chinese PLA General Hospital Department of Thoracic Surgery Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong University Burning Rock Biotech CAMS Key Laboratory of Translational Research on Lung Cancer State Key Laboratory of Molecular OncologyDepartment of Medical OncologyNational Cancer Center/National Clinical Research Center for ancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College Institute of Basic Medicine and Cancer (IBMC) Chinese Academy of Sciences Department of clinical trial The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)

In non-small cell lung cancers,the non-squamous and squamous subtypes（nsqNSCLC and sqNSCLC） exhibit disparities in pathophysiology,tumor immunology,and potential genomic correlates affecting responses to immune checkpoint inhibitor（ICI）-based *** our inhouse training cohort（n=85）,the presence of the LRP1B deleterious mutation（LRP1B-del） was associated with longer and shorter progression-free survival（PFS） on ICIs alone in nsqNSCLCs and sqNSCLCs,respectively(Pinteraction=0.008).These results were validated using a larger public ICI cohort(n=208,Pinteractionclinical utility of LRP1B-del in guiding treatment choices for nsqNSCLCs and sqNSCLCs,emphasizing the necessity for a detailed analysis based on pathological subtypes when investigating biomarkers for cancer therapeutics.

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Effects of raloxifene hydrochloride on bone mineral density, bone metabolism and serum lipids in Chinese postmenopausal women with osteoporosis: a multi-center, randomized, placebo-controlled clinical trial

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Chinese Medical Journal 2004年第7期117卷 1029-1035页

作者：刘建立朱汉民黄琪仁张忠兰李慧林秦跃娟张颖魏道林陆敬辉刘慧陈小平刘玉娟 Abie Ekangaki 郑以漫 Adolfo Diez-Perez Kristine Harper Department of Obstetrics and Gynaecology Department of Gerontology center for Preventing and Treating Osteoporosis Eli Lilly and Company

Background Raloxifene has been approved for prevention and treatment of postmenopausal osteoporosis in Caucasian women. It also has some positive effects on serum lipids in Caucasians. The objective of this study was to determine the effect of raloxifene hydrochloride on lumbar spine and total hip bone mineral density (BMD), bone metabolism, and serum lipids in Chinese postmenopausal women with *** This was a multi-center, randomized, double-blind, placebo-controlled clinical trial in which 204 postmenopausal Chinese women with osteoporosis were assigned to receive raloxifene (60 mg) or placebo treatment daily for 12 months. BMD, serum bone metabolism markers, and serum lipids were measured before and after drug administration. BMD was measured by Dual-Energy X-Ray Absorptiometry (DEXA) and bone metabolism markers were analyzed by one-step enzyme-linked immunosorbent assay. Serum lipids were measured by enzymatic *** At the end of the 12-month study, lumbar spine BMD increased in both groups with a mean increase of (3.3±4.8) % in the raloxifene group and (1.0±4.9) % in the placebo group (P0.05). In the raloxifene group, the median decreases in the biochemical markers of bone metabolism serum osteocalcin and C-telopeptide were 41.7% and 61.5%, respectively. These changes were statistically significant compared with those in the placebo group (10.6% and 35.6%, P<0.001, respectively). Both total cholesterol and low-density lipoprotein cholesterol decreased significantly in the raloxifene group compared with those in the placebo group (P<0.001, respectively) and there was no significant effect of raloxifene on high-density lipoprotein cholesterol and triglycerides compared

关键词： raloxifene · bone density · bone metabolism markers · osteoporosis postmenopausal

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Understanding the link between type 2 diabetes mellitus and Parkinson's disease:role of brain insulin resistance

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Neural Regeneration Research 2025年第11期20卷 3113-3123页

作者： Theodora Ntetsika Sergiu-Bogdan Catrina Ioanna Markaki Department of clinical Neuroscience Karolinska InstituteStockholmSweden Department of Neurology Karolinska University HospitalStockholmSweden Department of Molecular Medicine and Surgery Karolinska InstituteStockholmSweden center for Diabetes Academic Specialist CenterStockholmSweden center for Neurology Academic Specialist CenterStockholmSweden

Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic *** data supporting a close relationship between these two aging-related diseases have resulted in the investigation of shared pathophysiological molecular *** insulin signaling in the brain has gained increasing attention during the last decade and has been suggested to contribute to the development of Parkinson's disease through the dysregulation of several pathological *** contribution of type 2 diabetes mellitus and insulin resistance in neurodegeneration in Parkinson's disease,with emphasis on brain insulin resistance,is extensively discussed in this article and new therapeutic strategies targeting this pathological link are presented and reviewed.

关键词： brain insulin resistance brain insulin signaling diabetes type 2 GLP-1 receptor agonists GLP-1 signaling insulin resistance insulin signaling neurodegeneration Parkinson's disease targeted therapy

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Inhibitory gamma-aminobutyric acidergic neurons in the anterior cingulate cortex participate in the comorbidity of pain and emotion

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Neural Regeneration Research 2025年第10期20卷 2838-2854页

作者： Lu Guan Mengting Qiu Na Li Zhengxiang Zhou Ru Ye Liyan Zhong Yashuang Xu Junhui Ren Yi Liang Xiaomei Shao Jianqiao Fang Junfan Fang Junying Du Department of Neurobiology and Acupuncture Research Third School of Clinical MedicineZhejiang Chinese Medical UniversityHangzhouZhejiang ProvinceChina Key Laboratory for Research of Acupuncture Treatment and Transformation of Emotional Diseases Third School of Clinical MedicineZhejiang Chinese Medical UniversityHangzhouZhejiang ProvinceChina Fuchun Community Health Service center of Fuyang District HangzhouZhejiang ProvinceChina

Pain is often comorbid with emotional disorders such as anxiety and *** of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid *** review primarily aims to outline the main circuitry(including the input and output connectivity)of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons;it also describes the neurotransmitters/neuromodulators affecting these neurons,their intercommunication with other neurons,and their importance in mental comorbidities associated with chronic pain *** understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these ***,the mechanisms that regulate gamma-aminobutyric acidergic systems remain *** is also unclear as to whether the mechanisms are presynaptic or *** exploration of the complexities of this system may reveal new pathways for research and drug development.

关键词： anterior cingulate cortex anxiety chronic pain circuit communication comorbidity depression gamma-aminobutyric acidergic neurons parvalbumin neurons synaptic transmission

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Recent progress in the applications of presynaptic dopaminergic positron emission tomography imaging in parkinsonism

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Neural Regeneration Research 2025年第1期20卷 93-106页

作者： Yujie Yang Xinyi Li Jiaying Lu Jingjie Ge Mingjia Chen Ruixin Yao Mei Tian Jian Wang Fengtao Liu Chuantao Zuo Key Laboratory of Arrhythmias Ministry of EducationDepartment of Medical GeneticsShanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina Department of Neurology National Research Center for Aging and MedicineNational Center for Neurological Disordersand State Key Laboratory of Medical NeurobiologyHuashan HospitalFudan UniversityShanghaiChina Department of Nuclear Medicine&PET center National Center for Neurological Disordersand National Clinical Research Center for Aging and MedicineHuashan HospitalFudan UniversityShanghaiChina International Human Phenome Institutes(Shanghai) ShanghaiChina Human Phenome Institute Fudan UniversityShanghaiChina

Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of *** review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest *** conducted a thorough literature search using reputable databases such as PubMed and Web of *** criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical *** findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting ***,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo *** validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic *** summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.

关键词： aromatic amino acid decarboxylase brain imaging dopamine transporter Parkinson’s disease parkinsonism positron emission tomography presynaptic dopaminergic function vesicle monoamine transporter type 2

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Decreased levels of phosphorylated synuclein in plasma are correlated with poststroke cognitive impairment

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Neural Regeneration Research 2025年第9期20卷 2598-2610页

作者： Yi Wang Yuning Li Yakun Gu Wei Ma Yuying Guan Mengyuan Guo Qianqian Shao Xunming Ji Jia Liu Department of clinical Laboratory Beijing Bo’ai HospitalChina Rehabilitation Research CenterCapital Medical UniversityBeijingChina Beijing Institute of Brain Disorders Laboratory of Brain DisordersMinistry of Science and TechnologyCollaborative Innovation Center for Brain DisordersBeijing Advanced Innovation Center for Big Data-based Precision MedicineCapital Medical UniversityBeijingChina Department of Neurosurgery Xuanwu HospitalCapital Medical UniversityBeijingChina

Poststro ke cognitive impairment is a major secondary effect of ischemic stroke in many patients;however,few options are available for the early diagnosis and treatment of this *** aims of this study were to(1)determine the specific relationship between hypoxic andα-synuclein during the occur of poststroke cognitive impairment and(2)assess whether the serum phosphorylatedα-synuclein level can be used as a biomarker for poststro ke cognitive *** found that the phosphorylatedα-synuclein level was significantly increased and showed pathological aggregation around the cerebral infa rct area in a mouse model of ischemic *** addition,neuronalα-synuclein phosphorylation and aggregation were observed in the brain tissue of mice subjected to chronic hypoxia,suggesting that hypoxia is the underlying cause ofα-synuclein-mediated pathology in the brains of mice with ischemic *** phosphorylatedα-synuclein levels in patients with ischemic stroke were significantly lower than those in healt hy subjects,and were positively correlated with cognition levels in patients with ischemic ***,a decrease in serum high-density lipoprotein levels in stroke patie nts was significantly correlated with a decrease in phosphorylatedα-synuclein *** ischemic stroke mice did not show significant cognitive impairment or disrupted lipid metabolism 14 days after injury,some of them exhibited decreased cognitive function and reduced phosphorylatedα-synuclein *** together,our results suggest that serum phosphorylatedα-synuclein is a potential biomarker for poststroke cognitive impairment.

关键词： biomarker high-density lipoprotein ischemic stroke phosphorylatedα-synuclein poststroke cognitive impairment

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