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The burden of upper motor neuron involvement is correlated with the bilateral limb involvement interval in patients with amyotrophic lateral sclerosis:a retrospective observational study

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Neural Regeneration Research 2025年第5期20卷 1505-1512页

作者： Jieying Wu Shan Ye Xiangyi Liu Yingsheng Xu Dongsheng Fan Department of Neurology Peking University Third HospitalBeijingChina Beijing Municipal key laboratory of Biomarker and Translational Research in Neurodegenerative Diseases BeijingChina key laboratory for Neuroscience National Health Commission/Ministry of EducationPeking UniversityBeijingChina

Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor *** bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to ***,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is *** address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral *** used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis *** factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb *** results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis *** findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.

关键词： amyotrophic lateral sclerosis bilateral limb involvement Cox proportional hazards regression model horizontal spread restricted cubic spline analysis time interval upper motor neuron vertical spread

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Efficacy,safety and treatment satisfaction of transition to a regimen of insulin degludec/aspart:A pilot study

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World Journal of Diabetes 2025年第1期16卷 65-73页

作者： Na Yang Lu Lv Shu-Meng Han Li-Yun He Zi-Yi Li Yu-Cheng Yang Fan Ping Ling-Ling Xu Wei Li Hua-Bing Zhang Yu-Xiu Li Department of Endocrinology Key Laboratory of Endocrinology of National Health CommissionPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Allergy Beijing Key Laboratory of Precision Medicine for Diagnosis and Treatment of Allergic DiseasesNational Clinical Research Center for Dermatologic and Immunologic DiseasesPeking Union Medical College HospitalChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100730China

BACKGROUND There is a lack of clinical evidence on the efficacy and safety of transitioning from a thrice-daily pre-mixed insulin or basal-prandial regimen to insulin degludec/aspart(IDegAsp)therapy,with insufficient data from the Chinese *** To demonstrate the efficacy,safety,and treatment satisfaction associated with the transition to IDegAsp in type 2 diabetes mellitus(T2DM).METHODS In this 12-week open-label,non-randomized,single-center,pilot study,patients with T2DM receiving thrice-daily insulin or intensive insulin treatment were transitioned to twice-daily injections of insulin *** doses,hemoglobin A1c(HbA1c)levels,fasting blood glucose(FBG),hypoglycemic events,a Diabetes Treatment Satisfaction Questionnaire,and other parameters were assessed at baseline and *** This study included 21 participants.A marked enhancement was observed in the FBG level(P=0.02),daily total insulin dose(P=0.03),and overall diabetes treatment satisfaction(P<0.01)in the participants who switched to *** was a decrease in HbA1c levels(7.6±1.1 vs 7.4±0.9,P=0.31)and the frequency of hypoglycemic events of those who switched to IDegAsp decreased,however,there was no statistically significant *** The present findings suggest that treatment with IDegAsp enhances clinical outcomes,particularly FBG levels,daily cumulative insulin dose,and overall satisfaction with diabetes treatment.

关键词： Insulin degludec/aspart Type 2 diabetes management Basal-bolus insulin therapy Pre-mixed insulin Diabetes treatment satisfaction questionnaire

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Sequencing the Complete Genome of COVID-19 Virus from Clinical Samples Using the Sanger Method

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China CDC weekly 2020年第25期2卷 447-452页

作者： Roujian Lu Peihua Niu Li Zhao Huijuan Wang Wenling Wang Wenjie Tan key laboratory of biosafety National Health and Family Planning CommissionNational Institute for Viral Disease Control and PreventionChina CDCBeijingChina

What is already known on this topic?Coronavirus disease 2019(COVID-19),a disease caused by a novel human coronavirus named the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)or COVID-19 virus,was reported in December *** genomes of the COVID-19 virus from clinical samples using next generation sequencing(NGS)have been *** is added by this report?Here we provide the technical data for sequencing complete genome of COVID-19 virus from clinical samples using the Sanger *** complete COVID-19 virus genome sequences(named WH19004-S and GX0002)were obtained from clinical samples of COVID-19 patients,and two single nucleotide polymorphisms(SNPs)in ORF7a(T/C,nt 27,493)and ORF8(T/C,nt 28,253)of WH19004-S were identified by Sanger *** are the implications for public health practice?The COVID-19 virus genome sequencing by Sanger method reported here could be used to generate data of high enough quality without requirement for expensive NGS equipment,which support sequencing complete genomes from clinical samples and monitoring of viral genetic variations of COVID-19 infections.

关键词： Sanger clinical acute

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Three Novel Real-Time RT-PCR Assays for Detection of COVID-19 Virus

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China CDC weekly 2020年第25期2卷 453-457页

作者： Peihua Niu Roujian Lu Li Zhao Huijuan Wang Baoying Huang Fei Ye Wenling Wang Wenjie Tan key laboratory of biosafety National Health and Family Planning CommissionNational Institute for Viral Disease Control and PreventionChina CDCBeijingChina

What is already known on this topic?A novel human coronavirus,known as SARS-CoV-2 or 2019-nCoV,is the causative agent of the coronavirus disease 2019(COVID-19).We have released the primers and probes of real-time reverse transcription polymerase chain reaction(rRT-PCR)assays for the laboratory detection of COVID-19 *** is added by this report?Here we provide detailed technical data and evaluate the performance of three novel rRT-PCR assays targeting the ORF1ab,N,and E genes for detection of COVID-19 *** application of rRT-PCR assays among four types of specimens(alveolar lavage,sputum,throat swabs,and stool)from patients with COVID-19 indicated that the mean viral loads detected in sputum were higher than other *** are the implications for public health practice?These rRT-PCR assays reported here could be used for laboratory diagnosis of COVID-19 infection with high sensitivity,specificity,and *** rather than throat swabs and stool should be a priority for specimen collection for laboratory detection of COVID-19.

关键词： diagnosis specificity stool

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Cobalamin-dependent radical S-adenosyl-L-methionine protein functions with a partner to successively methylate tricyclic indole alkaloid for chuangxinmycin maturation and derivatization

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Science China Chemistry 2025年第01期 308-316页

作者： Sili Wang Jiancheng Huang Yanan Du Wei Huang Yufeng Xue Xiaokun Xu Guannan Zhong Yuanyuan Shi Bin Hong Xiaoying Bian Wen Liu State key laboratory of Chemical Biology Shanghai Institute of Organic Chemistry University of Chinese Academy of SciencesChinese Academy of Sciences State key laboratory of Microbial Technology Shandong University national health commission (NHC) key laboratory of Biotechnology for Microbial Drugs Institute of Medicinal BiotechnologyChinese Academy of Medical Science & Peking Union Medical College

Cobalamin(Cbl)-dependent radical S-adenosyl-L-methionine(SAM) proteins constitute the largest collection of the radical SAM superfamily that has hundreds of thousands of individual members. Many of these proteins are involved in the biosynthesis of pharmaceutically important natural products to catalyze chemically demanding reactions. In the biosynthetic pathway of chuangxinmycin(CXM), a unique indole alkaloid antibiotic with potent anti-infective activity, functionalization of the characteristic thiopyrano[4,3,2-cd]indole scaffold by regio-and stereoselective C3-methylation is believed to rely on a Cbl-dependent radical process, which, however, remained to be reconstituted biochemically. We here report the dissection of this enzymatic process, which requires the incorporation of Cxm8, a Cbl-dependent radical SAM protein, with Cxm9, a DUF5825family protein that shares no homology to any proteins of known functions. Cxm8 and Cxm9 function together by forming an unexpected heterodimeric complex that selectively catalyzes C3-methylation of the tricyclic indole-S-hetero ring system in a successive manner, achieving CXM and a recently identified, C3-dimethylated congener. Detailed biochemical characterization,isotope labeling, structural simulation and bioinformatics analysis rationalized the catalysis of the Cxm8/Cxm9 complex and particularly the necessity of the DUF5825 protein for C3-methylase activity. This is the first example that a Cbl-dependent protein acts with a partner to exhibit radical SAM activity.

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Neglected Zoonotic Monkeypox in Africa but Now Back in the Spotlight Worldwide

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China CDC weekly 2022年第38期4卷 847-848页

作者： Wenjie Tan George F.Gao key laboratory of biosafety National Health CommissionNational Institute for Viral Disease Control and PreventionChina CDCBeijingChina

On July 23,2022,the World health Organization(WHO)Director-General,*** Adhanom Ghebreyesus claimed monkeypox a Public health Emergency of International Concern(PHEIC),the 7th such an event in the 21st century(1).This is an alarming challenge to the world while we are still combating the coronavirus disease 2019(COVID-19)*** mid-August,approximately 40 thousand cases had been reported in more than 89 nations and regions worldwide(2).

关键词： Director claimed World

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De novo synthesis of atropisomeric benzofurans via Cu/SPDO complex catalyzed asymmetric formal [3 + 2] annulation

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Science China Chemistry 2025年第01期 174-180页

作者： Fan-Xiao Meng Xing-Yu Wang Ka Lu Ju-Song Yang Fu-Min Zhang Ai-Jun Ma Bao Du Yong-Qiang Tu State key laboratory of Applied Organic Chemistry College of Chemistry and Chemical Engineering Lanzhou University School of Chemistry and Chemical Engineering Shanghai Jiao Tong University School of Biotechnology and health Sciences Wuyi University

Herein, the de novo synthesis of atropisomeric benzofurans through the Cu/spirocyclic-pyrrolidine-oxazoline(SPDO) complex catalyze asymmetric formal [3 + 2] cycloaddition between quinones and ynamides is explored, producing a range of structurally diverse axially chiral benzofurans in satisfactory yields with good to excellent enantioselectivities. Furthermore, density functional theory calculations were applied to explain the possible reaction mechanism.

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Novaferon Effectively Inhibits Ancestral SARS-CoV-2 and Omicron Variant in Vitro,2022

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China CDC weekly 2022年第23期4卷 509-512页

作者： Fei Ye Baoying Huang Li Zhao Yao Deng Jiao Ren Wenjie Tan national health commission(NHC)key laboratory of biosafety National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina

Introduction:To identify Novaferon(Nova),a novel recombinant protein of interferon(IFN)-α,antiviral activity against ancestral severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and Omicron variant in ***:Vero cells were infected with SARSCoV-2 and Omicron variant in a biosafety level-3 *** viral replications were accessed using quantitative real-time reverse transcription polymerase chain reaction(RT-PCR).Results:Results demonstrated that Nova has effective inhibition against ancestral SARS-CoV-2 and Omicron variant in ***:The in vivo effects of Nova need to be further tested in animal *** large-scale randomized double-blind clinical trials are needed to reveal its potentially clinical application.

关键词： feron interferon clinical

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Peripheral mitochondrial DNA as a neuroinflammatory biomarker for major depressive disorder

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Neural Regeneration Research 2025年第6期20卷 1541-1554页

作者： Jinmei Ye Cong Duan Jiaxin Han Jinrong Chen Ning Sun Yuan Li Tifei Yuan Daihui Peng Division of Mood Disorder Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Department of Psychiatry First Hospital of Shanxi Medical UniversityTaiyuanShanxi ProvinceChina Shanghai key laboratory of Psychotic Disorders Brain Health InstituteNational Center for Mental DisordersShanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Co-Innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina

In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.

关键词： biomarker cytokine exosomes inflammasome major depressive disorder microglia mitochondrial DNA mitochondrial dysfunction neuroinflammation Toll-like receptor

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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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