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The development and benefits of metformin in various diseases

《医学前沿（英文）》 2023年 第17卷 第3期   页码 388-431 doi: 10.1007/s11684-023-0998-6

摘要： Metformin has been used for the treatment of type II diabetes mellitus for decades due to its safety, low cost, and outstanding hypoglycemic effect clinically. The mechanisms underlying these benefits are complex and still not fully understood. Inhibition of mitochondrial respiratory-chain complex I is the most described downstream mechanism of metformin, leading to reduced ATP production and activation of AMP-activated protein kinase (AMPK). Meanwhile, many novel targets of metformin have been gradually discovered. In recent years, multiple pre-clinical and clinical studies are committed to extend the indications of metformin in addition to diabetes. Herein, we summarized the benefits of metformin in four types of diseases, including metabolic associated diseases, cancer, aging and age-related diseases, neurological disorders. We comprehensively discussed the pharmacokinetic properties and the mechanisms of action, treatment strategies, the clinical application, the potential risk of metformin in various diseases. This review provides a brief summary of the benefits and concerns of metformin, aiming to interest scientists to consider and explore the common and specific mechanisms and guiding for the further research. Although there have been countless studies of metformin, longitudinal research in each field is still much warranted.

关键词： metformin     metabolism     cancer     aging     neurological disorder    

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Translational application of neuroimaging in major depressive disorder: a review of psychoradiological

Ziqi Chen, Xiaoqi Huang, Qiyong Gong, Bharat B. Biswal

《医学前沿（英文）》 2021年 第15卷 第4期   页码 528-540 doi: 10.1007/s11684-020-0798-1

摘要： Major depressive disorder (MDD) causes great decrements in health and quality of life with increments in healthcare costs, but the causes and pathogenesis of depression remain largely unknown, which greatly prevent its early detection and effective treatment. With the advancement of neuroimaging approaches, numerous functional and structural alterations in the brain have been detected in MDD and more recently attempts have been made to apply these findings to clinical practice. In this review, we provide an updated summary of the progress in translational application of psychoradiological findings in MDD with a specified focus on potential clinical usage. The foreseeable clinical applications for different MRI modalities were introduced according to their role in disorder classification, subtyping, and prediction. While evidence of cerebral structural and functional changes associated with MDD classification and subtyping was heterogeneous and/or sparse, the ACC and hippocampus have been consistently suggested to be important biomarkers in predicting treatment selection and treatment response. These findings underlined the potential utility of brain biomarkers for clinical practice.

关键词： psychoradiology     major depressive disorder     MRI     biomarker    

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Relationship between expression of hepatocyte grow factor and apoptosis of trophoblasts in hypertensive disorder

OUYANG Shan, ZHANG Qinghua, QIAO Fuyuan

《医学前沿（英文）》 2007年 第1卷 第4期   页码 386-389 doi: 10.1007/s11684-007-0075-6

摘要： The aim of this study was to investigate the expression of hepatocyte growth factor (HGF) and Fas in placentas of uncomplicated pregnant women and those with hypertensive disorder complicating pregnancy (HDCP), and elucidate the possible relationship between HGF and apoptosis of trophoblasts. Reverse transcription-polymerase chain reaction (RT-PCR) was undertaken to examine the concentration of HGF mRNA and Fas mRNA obtained from 34 cases of HDCP and 30 cases of uncomplicated pregnancy. The expression of HGF mRNA in mild preeclampsia, severe preeclampsia and eclampsia cases was significantly lower than that in the uncomplicated cases (0.43±0.12, 0.38±0.09, 0.19±0.17 versus 0.67±0.19, <0.05), while the expression of Fas mRNA in mild preeclampsia, severe preeclampsia and eclampisa cases was significantly higher than that in the uncomplicated cases (1.58±0.26, 2.96±0.14, 5.98±1.17 versus 1.01±0.36, <0.05). For HGF mRNA and Fas mRNA, there was no difference between gestational hypertension cases and control cases. Decreased HGF mRNA or increased Fas mRNA was found along with the progress of HDCP. Negative correlation was found between the expressions of HGF and Fas. These results indicate that HGF inhibits the apoptosis mediated by Fas, and the reduced expression of HGF in HDCP may be responsible for the apoptosis of trophoblasts.

关键词： pregnancy     concentration     possible relationship     responsible     hepatocyte    

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Overexpression of netrin-1 improves neurological outcomes in mice following transient middle cerebral

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《医学前沿（英文）》 2011年 第5卷 第1期   页码 86-93 doi: 10.1007/s11684-011-0118-x

摘要：

Netrin-1 (NT-1) is one of the axon-guiding molecules that are critical for neuronal development. Because of its structural homology to the endothelial mitogens, NT-1 may have similar effects on vascular network formation. NT-1 was shown to be able to stimulate the proliferation and migration of human cerebral endothelial cells in vitro and also promote focal neovascularization in adult brain in vivo. In the present study, we reported the delivery of NT-1 using an adeno-associated virus (AAV) vector (AAV-NT-1) into mouse brain followed by transient middle cerebral artery occlusion (tMCAO). We found that AAV vectors did not elicit a detectable inflammatory response, cell loss or neuronal damage after brain transduction. The level of NT-1 was increased in the AAV-NT-1-transduced tMCAO mice compared with the control mice. Furthermore, the neurobehavioral outcomes were significantly improved in AAV-NT-1-transduced mice compared with the control animals (P<0.05) 7 days after tMCAO. Our data suggests that NT-1 plays a neuronal function recovery role in ischemic brain and that NT-1 gene transfer might present a valuable approach to treat brain ischemic disorders.

关键词： adeno-associated virus     angiogenesis     gene transfer     ischemia     middle cerebral artery occlusion     netrin-1    

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肠道菌群是调节神经系统功能紊乱的潜在靶点 Review

武万强, 孔庆敏, 田培郡, 翟齐啸, 王刚, 刘小鸣, 赵建新, 张灏, Yuan Kun Lee, 陈卫

《工程（英文）》 2020年 第6卷 第4期   页码 415-423 doi: 10.1016/j.eng.2019.07.026

摘要：

众所周知，肠道菌群在调节宿主生理功能方面具有重要作用，如调节免疫和代谢平衡。近年来，越来越多证据表明肠道菌群能够通过肠-脑轴调节中枢神经系统功能，这为研究肠道和大脑间的相互作用关系开辟了一条新路径。本文首先介绍了肠道菌群与大脑相互作用的肠–脑轴分子机制，以及肠道菌群失调引发的神经系统功能紊乱；然后介绍了调节肠道菌群失衡是干预神经系统功能紊乱的潜在策略，如益生菌、益生元、合生元以及饮食等干预措施。目前关于肠道菌群–肠–脑轴方面的研究尚处在起步阶段，但继续深入阐明肠道菌群调节神经系统功能的分子机制不仅能揭示神经系统功能紊乱的新型病理机制，而且能够为神经系统功能紊乱提供潜在的诊断标志物和干预策略。

关键词： 肠道菌群     肠-脑轴     神经系统功能紊乱     干预策略    

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Neurological manifestations of patients with COVID-19: potential routes of SARS-CoV-2 neuroinvasion from

Zhengqian Li, Taotao Liu, Ning Yang, Dengyang Han, Xinning Mi, Yue Li, Kaixi Liu, Alain Vuylsteke, Hongbing Xiang, Xiangyang Guo

《医学前沿（英文）》 2020年 第14卷 第5期   页码 533-541 doi: 10.1007/s11684-020-0786-5

摘要： Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a global pandemic in only 3 months. In addition to major respiratory distress, characteristic neurological manifestations are also described, indicating that SARS-CoV-2 may be an underestimated opportunistic pathogen of the brain. Based on previous studies of neuroinvasive human respiratory coronaviruses, it is proposed that after physical contact with the nasal mucosa, laryngopharynx, trachea, lower respiratory tract, alveoli epithelium, or gastrointestinal mucosa, SARS-CoV-2 can induce intrinsic and innate immune responses in the host involving increased cytokine release, tissue damage, and high neurosusceptibility to COVID-19, especially in the hypoxic conditions caused by lung injury. In some immune-compromised individuals, the virus may invade the brain through multiple routes, such as the vasculature and peripheral nerves. Therefore, in addition to drug treatments, such as pharmaceuticals and traditional Chinese medicine, non-pharmaceutical precautions, including facemasks and hand hygiene, are critically important.

关键词： coronavirus disease 2019 (COVID-19)     SARS-CoV-2     neurological manifestations     neuroinvasion     brain    

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A rare case of B-lymphoproliferative disorder with villous lymphocytes harboring t(8;14)(q24;q32) translocation

null

《医学前沿（英文）》 2018年 第12卷 第3期   页码 324-329 doi: 10.1007/s11684-017-0558-z

摘要：

Splenic lymphoma with villous lymphocytes (SLVL) or splenic marginal zone lymphoma with circulating villous lymphocytes is rare, and prolymphocytic transformation of SLVL is rarer. At present, only one case of SLVL with t(8;14)(q24;q32) translocation has been reported. In this study, we report a case of B-lymphoproliferative disorder with villous lymphocytes harboring t(8;14)(q24;q32) chromosome translocation that we inclined to SLVL with a prolymphocytic transformation. A 73-year-old female showed marked hepatosplenomegaly and high lymphocytosis (lymphocytes>200×109/L). The abnormal lymphocytes had short coarse villi and round nuclei with prominent nucleoli. The immunophenotypes showed CD19+, CD20+, HLA-DR+, CD22+, CD5+, Kappa+, CD25dim, CD71dim, Lambda−, CD7−, CD10−, CD23−, CD34−, CD33−, CD13−, CD14−, CD117−, CD64−, CD103−, and CD11c−. The karyotype showed complex abnormality: 46XX,+3,−10, t(8;14)(q24;q32)[11]/46XX[9]. The cytoplasmic projection, immunological characteristics, and trisomy 3 chromosome abnormality supported the diagnosis of SLVL. However, the presence of prominent nucleoli and high lymphocytosis suggested prolymphocytic transformation, probably as a result of t(8,14) chromosome translocation. In this report, we described an unusual case of B-lymphoproliferative disorder with villous lymphocytes harboring t(8;14)(q24;q32) translocation, which could provide help in the diagnosis and differential diagnosis of B-lymphocytic proliferative diseases.

关键词： splenic lymphoma with villous lymphocytes     splenic marginal zone lymphoma     transformation     chromosome translocation    

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Cytokines and inflammation in adipogenesis: an updated review

Ning Jiang, Yao Li, Ting Shu, Jing Wang

《医学前沿（英文）》 2019年 第13卷 第3期   页码 314-329 doi: 10.1007/s11684-018-0625-0

摘要： The biological relevance of cytokines is known for more than 20 years. Evidence suggests that adipogenesis is one of the biological events involved in the regulation of cytokines, and pro-inflammatory cytokines (e.g., TNF and IL-1 ) inhibit adipogenesis through various pathways. This inhibitory effect can constrain the hyperplastic expandability of adipose tissues. Meanwhile, chronic low-grade inflammation is commonly observed in obese populations. In some individuals, the impaired ability of adipose tissues to recruit new adipocytes to adipose depots during overnutrition results in adipocyte hypertrophy, ectopic lipid accumulation, and insulin resistance. Intervention studies showed that pro-inflammatory cytokine antagonists improve metabolism in patients with metabolic syndrome. This review focuses on the cytokines currently known to regulate adipogenesis under physiological and pathophysiological circumstances. Recent studies on how inhibited adipogenesis leads to metabolic disorders were summarized. Although the interplay of cytokines and lipid metabolism is yet incompletely understood, cytokines represent a class of potential therapeutic targets in the treatment of metabolic disorders.

关键词： cytokines     inflammation     adipogenesis     type 2 diabetes mellitus     metabolic disorder    

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我国人群血脂水平现状及其对策

陈灏珠,金雪娟

《中国工程科学》 2002年 第4卷 第11期   页码 1-6

摘要：

回顾分析50年来我国健康人群血脂水平的变化，结果显示血总胆固醇（TC）、甘油三酯（TG）和低密度脂蛋白胆固醇（LDL-C）随年龄而增高,50岁以前男女间无差别,50岁以后女性高于男性,城市居民高于农村居民；高密度脂蛋白胆固醇（HDL-C）随年龄的变化不明显,男性低于女性；血TC、TG和LDL-C随年代而增高,20世纪90年代末达最高峰,而HDL-C则下降；血TC高于正常者（＞200～220 mg/dL）男性占17.8 %～54.9 %,女性占14.9 %～53.4 %，也随年代而增多；血脂水平的变化与饮食结构转变为低碳水化合物、高脂肪、高胆固醇有关。对策:恢复健康的饮食习惯,摄取平衡饮食；建立良好生活习惯，减少其他心血管病危险因素,特别建议进行体育锻炼；已有血脂异常,经饮食调节和体育锻炼3个月以上仍未见好转者,宜接受调脂药物治疗。

关键词： 血脂     流行病学     预防    

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Panoramic variation analysis of a family with neurodevelopmental disorders caused by biallelic loss-of-function variants in , , and

《医学前沿（英文）》 doi: 10.1007/s11684-023-1006-x

摘要： Highly clinical and genetic heterogeneity of neurodevelopmental disorders presents a major challenge in clinical genetics and medicine. Panoramic variation analysis is imperative to analyze the disease phenotypes resulting from multilocus genomic variation. Here, a Pakistani family with parental consanguinity was presented, characterized with severe intellectual disability (ID), spastic paraplegia, and deafness. Homozygosity mapping, integrated single nucleotide polymorphism (SNP) array, whole-exome sequencing, and whole-genome sequencing were performed, and homozygous variants in TMEM141 (c.270G>A, p.Trp90*), DDHD2 (c.411+767_c.1249-327del), and LHFPL5 (c.250delC, p.Leu84*) were identified. A Tmem141p.Trp90*/p.Trp90* mouse model was generated. Behavioral studies showed impairments in learning ability and motor coordination. Brain slice electrophysiology and Golgi staining demonstrated deficient synaptic plasticity in hippocampal neurons and abnormal dendritic branching in cerebellar Purkinje cells. Transmission electron microscopy showed abnormal mitochondrial morphology. Furthermore, studies on a human in vitro neuronal model (SH-SY5Y cells) with stable shRNA-mediated knockdown of TMEM141 showed deleterious effect on bioenergetic function, possibly explaining the pathogenesis of replicated phenotypes in the cross-species mouse model. Conclusively, panoramic variation analysis revealed that multilocus genomic variations of TMEM141, DDHD2, and LHFPL5 together caused variable phenotypes in patient. Notably, the biallelic loss-of-function variants of TMEM141 were responsible for syndromic ID.

关键词： neurodevelopmental disorder     autosomal recessive intellectual disability     consanguinity     spastic paraplegia     hearing loss     TMEM141    

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Identification of differentially expressed miRNAs associated with chronic kidney disease–mineral bone disorder

null

《医学前沿（英文）》 2017年 第11卷 第3期   页码 378-385 doi: 10.1007/s11684-017-0541-8

摘要：

The purpose of this study is to characterize a meta-signature of differentially expressed mRNA in chronic kidney disease (CKD) to predict putative microRNA (miRNA) in CKD–mineral bone disorder (CKD–MBD) and confirm the changes in these genes and miRNA expression under uremic conditions by using a cell culture system. PubMed searches using MeSH terms and keywords related to CKD, uremia, and mRNA arrays were conducted. Through a computational analysis, a meta-signature that characterizes the significant intersection of differentially expressed mRNA and expected miRNAs associated with CKD–MBD was determined. Additionally, changes in gene and miRNA expressions under uremic conditions were confirmed with human Saos-2 osteoblast-like cells. A statistically significant mRNA meta-signature of upregulated and downregulated mRNA levels was identified. Furthermore, miRNA expression profiles were inferred, and computational analyses were performed with the imputed microRNA regulation based on weighted ranked expression and putative microRNA targets (IMRE) method to identify miRNAs associated with CKD occurrence. TLR4 and miR-146b levels were significantly associated with CKD–MBD. TLR4 levels were significantly downregulated, whereas pri-miR-146b and miR-146b were upregulated in the presence of uremic toxins in human Saos-2 osteoblast-like cells. Differentially expressed miRNAs associated with CKD-MBD were identified through a computational analysis, and changes in gene and miRNA expressions were confirmed with an in vitro cell culture system.

关键词： chronic kidney disease     microRNA     mineral bone disorder     uremia    

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人体微生态与健康

王保红, 姚铭飞, 吕龙贤, 凌宗欣, 李兰娟

《工程（英文）》 2017年 第3卷 第1期   页码 71-82 doi: 10.1016/J.ENG.2017.01.008

摘要：

数以万亿计的微生物寄生于人体表面和体内，并与人类起演变多种环境因素可影响胃肠道微生的平衡，这些改变与人体健康和疾病密切相关本文重点关注人体微生与宿主之间的相互作用，总体概括微生物在人体基本生命过程中以及主要疾病中起的作用，如感染性疾病肝脏疾病胃肠道肿瘤、代谢疾病呼吸系统疾病精神或心理疾病和自身免疫疾病等。我们还综述了微生物研究相关术的重要进展，如DNA 测序、代谢组学和基于计算生物信息学的蛋白质组学目前对人类微生态的研究已经更加复杂和全面建议研究应更多关注–宿主微生物的相互作用和因果关系，这有助于我们更好地了解肠道微生物在人类健康和疾病中的作用，并为临床实践提供新的治疗靶点和方法。

关键词： 微生物     健康     传染病     肝病     胃肠道恶性肿瘤     代谢紊乱     微生物技术     益生菌    

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PET imaging on neurofunctional changes after optogenetic stimulation in a rat model of panic disorder

Xiao He, Chentao Jin, Mindi Ma, Rui Zhou, Shuang Wu, Haoying Huang, Yuting Li, Qiaozhen Chen, Mingrong Zhang, Hong Zhang, Mei Tian

《医学前沿（英文）》 2019年 第13卷 第5期   页码 602-609 doi: 10.1007/s11684-019-0704-x

摘要： Panic disorder (PD) is an acute paroxysmal anxiety disorder with poorly understood pathophysiology. The dorsal periaqueductal gray (dPAG) is involved in the genesis of PD. However, the downstream neurofunctional changes of the dPAG during panic attacks have yet to be evaluated . In this study, optogenetic stimulation to the dPAG was performed to induce panic-like behaviors, and positron emission tomography (PET) imaging with F-flurodeoxyglucose ( F-FDG) was conducted to evaluate neurofunctional changes before and after the optogenetic stimulation. Compared with the baseline, post-optogenetic stimulation PET imaging demonstrated that the glucose metabolism significantly increased ( <0.001) in dPAG, the cuneiform nucleus, the cerebellar lobule, the cingulate cortex, the alveus of the hippocampus, the primary visual cortex, the septohypothalamic nucleus, and the retrosplenial granular cortex but significantly decreased ( <0.001) in the basal ganglia, the frontal cortex, the forceps minor corpus callosum, the primary somatosensory cortex, the primary motor cortex, the secondary visual cortex, and the dorsal lateral geniculate nucleus. Taken together, these data indicated that PET imaging can successfully detect downstream neurofunctional changes involved in the panic attacks after optogenetic stimulation to the dPAG.

关键词： panic disorder (PD)     positron emission tomography (PET)     optogenetics     dorsal periaqueductal gray (dPAG)    

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两种特殊类型排卵障碍的超声监测和促排卵治疗疗效观察

刘莉,吴春林,胡雅君

《中国工程科学》 2015年 第17卷 第6期   页码 31-35

摘要：

目的：了解正常排卵、小卵泡排卵以及未破裂卵泡黄素化患者的临床特征及观察后两者经阴道B超再次监排情况和促排卵治疗效果。方法：回顾性分析了正常排卵组（258例）、小卵泡排卵组（65例）及未破裂卵泡黄素化组（27例）患者年龄、排卵前卵泡大小和基础性激素水平差异，观察了后两组排卵障碍患者经阴道B超再次监排情况。并对两次监排结果一致的58例小卵泡排卵和25例未破裂卵泡黄素化患者进行克罗米芬促排卵治疗，分别观察了这两种排卵障碍患者的正常排卵率及临床妊娠率。结果：正常排卵组、小卵泡排卵组和未破裂卵泡黄素化组患者平均年龄、基础性激素水平均无显著性差异。三组间排卵前卵泡最大平均径线有显著性差异（F=117.9，P<0.01）。小卵泡排卵和未破裂卵泡黄素化的发生率分别为18.57 %和7.71 %。两者再次监排后，再发率分别为89.23 %和92.59 %。经克罗米芬促排卵联合黄体支持治疗后，小卵泡排卵组和未破裂卵泡黄素化组正常排卵率分别为70.69 %和80 %，临床妊娠率分别为29.31 %和48 %。结论：年龄、基础性激素水平不能预测是否正常排卵，经阴道B超监测是诊断小卵泡排卵以及未破裂卵泡黄素化的直观方法。不经过治疗两者再发率高，促排卵治疗联合黄体支持是治疗小卵泡排卵以及未破裂卵泡黄素化的有效方法。

关键词： 经阴道超声；排卵监测；小卵泡排卵；未破裂卵泡黄素化；促排卵治疗    

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包容性工程——借助工程技术发明为身体或精神障碍人士赋能

Peter T. Cummings, Philippe M. Fauchet, Michael Goldfarb, Martha W.M. Jones, Maithilee Kunda, Jonathan B. Perlin, Nilanjan Sarkar, Keivan G. Stassun, Zachary E. Warren, Karl E. Zelik

《工程（英文）》 2021年 第7卷 第2期   页码 141-143 doi: 10.1016/j.eng.2020.06.020

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标题 作者 时间 类型 操作

The development and benefits of metformin in various diseases

期刊论文

Translational application of neuroimaging in major depressive disorder: a review of psychoradiological

Ziqi Chen, Xiaoqi Huang, Qiyong Gong, Bharat B. Biswal

期刊论文

Relationship between expression of hepatocyte grow factor and apoptosis of trophoblasts in hypertensive disorder

OUYANG Shan, ZHANG Qinghua, QIAO Fuyuan

期刊论文

Overexpression of netrin-1 improves neurological outcomes in mice following transient middle cerebral

null

期刊论文

肠道菌群是调节神经系统功能紊乱的潜在靶点

武万强, 孔庆敏, 田培郡, 翟齐啸, 王刚, 刘小鸣, 赵建新, 张灏, Yuan Kun Lee, 陈卫

期刊论文

Neurological manifestations of patients with COVID-19: potential routes of SARS-CoV-2 neuroinvasion from

Zhengqian Li, Taotao Liu, Ning Yang, Dengyang Han, Xinning Mi, Yue Li, Kaixi Liu, Alain Vuylsteke, Hongbing Xiang, Xiangyang Guo

期刊论文

A rare case of B-lymphoproliferative disorder with villous lymphocytes harboring t(8;14)(q24;q32) translocation

null

期刊论文

Cytokines and inflammation in adipogenesis: an updated review

Ning Jiang, Yao Li, Ting Shu, Jing Wang

期刊论文

我国人群血脂水平现状及其对策

陈灏珠,金雪娟

期刊论文

Panoramic variation analysis of a family with neurodevelopmental disorders caused by biallelic loss-of-function variants in , , and

期刊论文

Identification of differentially expressed miRNAs associated with chronic kidney disease–mineral bone disorder

null

期刊论文

人体微生态与健康

王保红, 姚铭飞, 吕龙贤, 凌宗欣, 李兰娟

期刊论文

PET imaging on neurofunctional changes after optogenetic stimulation in a rat model of panic disorder

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