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A review of the neurotransmitter system associated with cognitive function of the cerebellum in Parkinson's disease

Neural Regeneration Research 2024年第2期19卷 324-330页

作者： Xi Chen Yuhu Zhang Department of Neurology Guangdong Neuroscience InstituteGuangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong ProvinceChina Shantou university Medical College ShantouGuangdong ProvinceChina

The dichotomized brain system is a concept that was generalized from the‘dual syndrome hypothesis’to explain the heterogeneity of cognitive impairment,in which anterior and posterior brain systems are independent but partially overlap.The dopaminergic system acts on the anterior brain and is responsible for executive function,working memory,and planning.In contrast,the cholinergic system acts on the posterior brain and is responsible for semantic fluency and visuospatial function.Evidence from dopaminergic/cholinergic imaging or functional neuroimaging has shed significant insight relating to the involvement of the cerebellum in the cognitive process of patients with Parkinson’s disease.Previous research has reported evidence that the cerebellum receives both dopaminergic and cholinergic projections.However,whether these two neurotransmitter systems are associated with cognitive function has yet to be fully elucidated.Furthermore,the precise role of the cerebellum in patients with Parkinson’s disease and cognitive impairment remains unclear.Therefore,in this review,we summarize the cerebellar dopaminergic and cholinergic projections and their relationships with cognition,as reported by previous studies,and investigated the role of the cerebellum in patients with Parkinson’s disease and cognitive impairment,as determined by functional neuroimaging.Our findings will help us to understand the role of the cerebellum in the mechanisms underlying cognitive impairment in Parkinson’s disease.

关键词： anterior brain system cerebellum cholinergic cognitive impairment dopaminergic dual syndrome hypothesis neuroimage neurotransmitter Parkinson’s disease posterior brain system therapeutic targets

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Epidemiological Surveillance: Genetic Diversity of Rotavirus Group A in the Pearl River Delta, guangdong, China in 2019

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Biomedical and Environmental Sciences 2024年第3期37卷 278-293页

作者： JIANG Jie Ying LIANG Dan WANG Li XIAO Yun LIANG Yu Feng KE Bi Xia SU Juan XIAO Hong WANG Tao ZOU Min LI Hong Jian KE Chang Wen School of Public Health Shantou UniversityShantou 515063GuangdongChina guangdong Provincial Center for Disease Control and Prevention Guangdong Workstation for Emerging Infectious Disease Control and PreventionGuangzhou 511430GuangdongChina guangdong Provincial Key Laboratory of Virology Institute of Medical MicrobiologyJinan UniversityGuangzhou 510632GuangdongChina School of Public Health Sun Yat-sen UniversityGuangzhou 510275GuangdongChina School of Public Health Southern Medical UniversityGuangzhou 510515GuangdongChina Shantou university Medical College Shantou 515041GuangdongChina

Objective This study aimed to understand the epidemic status and phylogenetic relationships of rotavirus group A(RVA)in the Pearl River Delta region of guangdong Province,China.Methods This study included individuals aged 28 days–85 years.A total of 706 stool samples from patients with acute gastroenteritis collected between January 2019 and January 2020 were analyzed for 17 causative pathogens,including RVA,using a Gastrointestinal Pathogen Panel,followed by genotyping,virus isolation,and complete sequencing to assess the genetic diversity of RVA.Results The overall RVA infection rate was 14.59%(103/706),with an irregular epidemiological pattern.The proportion of co-infection with RVA and other pathogens was 39.81%(41/103).Acute gastroenteritis is highly prevalent in young children aged 0–1 year,and RVA is the key pathogen circulating in patients 6–10 months of age with diarrhea.G9P[8](58.25%,60/103)was found to be the predominant genotype in the RVA strains,and the 41 RVA-positive strains that were successfully sequenced belonged to three different RVA genotypes in the phylogenetic analysis.Recombination analysis showed that gene reassortment events,selection pressure,codon usage bias,gene polymorphism,and post-translational modifications(PTMs)occurred in the G9P[8]and G3P[8]strains.Conclusion This study provides molecular evidence of RVA prevalence in the Pearl River Delta region of China,further enriching the existing information on its genetics and evolutionary characteristics and suggesting the emergence of genetic diversity.Strengthening the surveillance of genotypic changes and gene reassortment in RVA strains is essential for further research and a better understanding of strain variations for further vaccine development.

关键词： Infectious diarrheal disease Rotavirus Phylogenetic analysis Gene rearrangement Codon usage bias Genetic diversity

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Interplay between microglia and environmental risk factors in Alzheimer's disease

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Neural Regeneration Research 2024年第8期19卷 1718-1727页

作者： Miaoping Zhang Chunmei Liang Xiongjin Chen Yujie Cai Lili Cui guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases Affiliated Hospital of Guangdong Medical UniversityZhanjiangGuangdong ProvinceChina

Alzheimer s disease,among the most common neurodegenerative disorders,is chara cterized by progressive cognitive impairment.At present,the Alzheimer’s disease main risk remains genetic ris ks,but major environmental fa ctors are increasingly shown to impact Alzheimer’s disease development and progression.Microglia,the most important brain immune cells,play a central role in Alzheimer’s disease pathogenesis and are considered environmental and lifestyle"sensors."Factors like environmental pollution and modern lifestyles(e.g.,chronic stress,poor dietary habits,sleep,and circadian rhythm disorde rs)can cause neuroinflammato ry responses that lead to cognitive impairment via microglial functioning and phenotypic regulation.However,the specific mechanisms underlying interactions among these facto rs and microglia in Alzheimer’s disease are unclear.Herein,we:discuss the biological effects of air pollution,chronic stress,gut micro biota,sleep patterns,physical exercise,cigarette smoking,and caffeine consumption on microglia;consider how unhealthy lifestyle factors influence individual susceptibility to Alzheimer’s disease;and present the neuroprotective effects of a healthy lifestyle.Toward intervening and controlling these environmental risk fa ctors at an early Alzheimer’s disease stage,understanding the role of microglia in Alzheimer’s disease development,and to rgeting strategies to to rget microglia,co uld be essential to future Alzheimer’s disease treatments.

关键词： Alzheimer’s disease chronic stress environmental factor gut microbiota microglia particulate matter with diameter<2.5μm

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Large deviation rates for supercritical multitype branching processes with immigration

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Acta Mathematica Sinica,English Series 2024年

作者： Liu Yan LI Jun Ping LI School of Statistics and Mathematics Guangdong University of Finance and Economics School of Mathematics and Statistics Central South University guangdong university of science and technology

Let{X_n}n≥0be a p-type （p≥2） supercritical branching process with immigration and mean matrix M.Suppose that M is positively regular andρis the maximal eigenvalue of M with the corresponding left and right eigenvectors v and u.Letρ>1 and ■,where the vectorλdenotes the mean immigration rate.In this paper,we will show that Ynis a martingale and converges to a r.v.Y as n→∞.We study the rates of convergence to 0 as n→∞of ■ for any ε>0,i=1,···,p,1=（1,···,1） and l∈Rp,the p-dimensional Euclidean space.It is shown that under certain moment conditions,the first two decay geometrically,while conditionally on the event Y≥α （α>0） supergeometrically.The decay rate of the last probability is always supergeometric under a finite moment generating function assumption.

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Artificial intelligence-based analysis of tumor-infiltrating lymphocyte spatial distribution for colorectal cancer prognosis

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Chinese Medical Journal 2024年第4期137卷 421-430页

作者： Ming Cai Ke Zhao Lin Wu Yanqi Huang Minning Zhao Qingru Hu Qicong Chen Su Yao Zhenhui Li Xinjuan Fan Zaiyi Liu Department of Radiology Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong 510080China guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application GuangzhouGuangdong 510080China guangdong Cardiovascular Institute Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong 510080China Medical Research Institute Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong 510080China Department of Pathology The Third Affiliated Hospital of Kunming Medical UniversityYunnan Cancer HospitalYunnan Cancer CenterKunmingYunnan 650118China The Second School of Clinical Medicine Southern Medical UniversityGuangzhouGuangdong 510515China Institute of Computing Science and Technology Guangzhou UniversityGuangzhouGuangdong 510006China Department of Pathology Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong 510080China Department of Pathology The Sixth Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510655China

Background:Artificial intelligence(AI)technology represented by deep learning has made remarkable achievements in digital pathology,enhancing the accuracy and reliability of diagnosis and prognosis evaluation.The spatial distribution of CD3^(+)and CD8^(+)T cells within the tumor microenvironment has been demonstrated to have a significant impact on the prognosis of colorectal cancer(CRC).This study aimed to investigate CD3_(CT)(CD3^(+)T cells density in the core of the tumor[CT])prognostic ability in patients with CRC by using AI technology.Methods:The study involved the enrollment of 492 patients from two distinct medical centers,with 358 patients assigned to the training cohort and an additional 134 patients allocated to the validation cohort.To facilitate tissue segmentation and T-cells quantification in whole-slide images(WSIs),a fully automated workflow based on deep learning was devised.Upon the completion of tissue segmentation and subsequent cell segmentation,a comprehensive analysis was conducted.Results:The evaluation of various positive T cell densities revealed comparable discriminatory ability between CD3_(CT) and CD3-CD8(the combination of CD3^(+)and CD8^(+)T cells density within the CT and invasive margin)in predicting mortality(C-index in training cohort:0.65 vs.0.64;validation cohort:0.69 vs.0.69).The CD3_(CT) was confirmed as an independent prognostic factor,with high CD3_(CT) density associated with increased overall survival(OS)in the training cohort(hazard ratio[HR]=0.22,95%confidence interval[CI]:0.12–0.38,P<0.001)and validation cohort(HR=0.21,95%CI:0.05–0.92,P=0.037).Conclusions:We quantify the spatial distribution of CD3^(+)and CD8^(+)T cells within tissue regions in WSIs using AI technology.The CD3_(CT) confirmed as a stage-independent predictor for OS in CRC patients.Moreover,CD3_(CT) shows promise in simplifying the CD3-CD8 system and facilitating its practical application in clinical settings.

关键词： Colorectal cancer Artificial intelligence Deep learning Digital pathology Prognosis Immune cells CD3 CD8 TME

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Genetically modified non-human primate models for research on neurodegenerative diseases

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Zoological Research 2024年第2期45卷 263-274页

作者： Ming-Tian Pan Han Zhang Xiao-Jiang Li Xiang-Yu Guo guangdong Key Laboratory of Non-human Primate Research Guangdong-Hongkong-Macao Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong 510632China

Neurodegenerative diseases(NDs)are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease(AD),Parkinson's disease(PD),Huntington's disease(HD),and amyotrophic lateral sclerosis(ALS).Currently,there are no therapies available that can delay,stop,or reverse the pathological progression of NDs in clinical settings.As the population ages,NDs are imposing a huge burden on public health systems and affected families.Animal models are important tools for preclinical investigations to understand disease pathogenesis and test potential treatments.While numerous rodent models of NDs have been developed to enhance our understanding of disease mechanisms,the limited success of translating findings from animal models to clinical practice suggests that there is still a need to bridge this translation gap.Old World nonhuman primates(NHPs),such as rhesus,cynomolgus,and vervet monkeys,are phylogenetically,physiologically,biochemically,and behaviorally most relevant to humans.This is particularly evident in the similarity of the structure and function of their central nervous systems,rendering such species uniquely valuable for neuroscience research.Recently,the development of several genetically modified NHP models of NDs has successfully recapitulated key pathologies and revealed novel mechanisms.This review focuses on the efficacy of NHPs in modeling NDs and the novel pathological insights gained,as well as the challenges associated with the generation of such models and the complexities involved in their subsequent analysis.

关键词： Neurodegeneration Non-human primate Macaque monkey Animal model Gene modification

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Integrated multi-omics analysis reveals liver metabolic reprogramming by fish iridovirus and antiviral function of alpha-linolenic acid

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Zoological Research 2024年第3期45卷 520-534页

作者： Lin Liu Ya Zhang Meng-Di Yuan Dong-Miao Xiao Wei-Hua Xu Qi Zheng Qi-Wei Qin You-Hua Huang Xiao-Hong Huang College of Marine Sciences South China Agricultural UniversityGuangdong Laboratory for Lingnan Modern AgricultureGuangzhouGuangdong 510642China Nansha-South China Agricultural university Fishery Research Institute GuangzhouGuangdong 511464China Southern Marine Science and Engineering guangdong Laboratory ZhuhaiGuangdong 519082China

Iridovirus poses a substantial threat to global aquaculture due to its high mortality rate;however,the molecular mechanisms underpinning its pathogenesis are not well elucidated.Here,a multi-omics approach was applied to groupers infected with Singapore grouper iridovirus(SGIV),focusing on the roles of key metabolites.Results showed that SGIV induced obvious histopathological damage and changes in metabolic enzymes within the liver.Furthermore,SGIV significantly reduced the contents of lipid droplets,triglycerides,cholesterol,and lipoproteins.Metabolomic analysis indicated that the altered metabolites were enriched in 19 pathways,with a notable down-regulation of lipid metabolites such as glycerophosphates and alpha-linolenic acid(ALA),consistent with disturbed lipid homeostasis in the liver.Integration of transcriptomic and metabolomic data revealed that the top enriched pathways were related to cell growth and death and nucleotide,carbohydrate,amino acid,and lipid metabolism,supporting the conclusion that SGIV infection induced liver metabolic reprogramming.Further integrative transcriptomic and proteomic analysis indicated that SGIV infection activated crucial molecular events in a phagosome-immune depression-metabolism dysregulation-necrosis signaling cascade.Of note,integrative multi-omics analysis demonstrated the consumption of ALA and linoleic acid(LA)metabolites,and the accumulation of L-glutamic acid(GA),accompanied by alterations in immune,inflammation,and cell death-related genes.Further experimental data showed that ALA,but not GA,suppressed SGIV replication by activating antioxidant and anti-inflammatory responses in the host.Collectively,these findings provide a comprehensive resource for understanding host response dynamics during fish iridovirus infection and highlight the antiviral potential of ALA in the prevention and treatment of iridoviral diseases.

关键词： Iridovirus Liver damage Metabolic reprogramming SGIV Alpha-linolenic acid Antiinflammatory

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Large animal models for Huntington's disease research

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Zoological Research 2024年第2期45卷 275-283页

作者： Bofeng Han Weien Liang Xiao-Jiang Li Shihua Li Sen Yan Zhuchi Tu guangdong-Hongkong-Macao CNS Regeneration Institute of Jinan university Key Laboratory of CNS Regeneration(Jinan University)-Ministry of EducationGuangdong Key Laboratory of Non-Human Primate ResearchGuangzhouGuangdong 510632China Department of Pathophysiology School of MedicineJinan UniversityGuangzhouGuangdong 510632China

Huntington'sdisease(HD)isahereditary neurodegenerative disorder for which there is currently no effectivetreatmentavailable.Consequently,the development of appropriate disease models is critical to thoroughly investigate disease progression.The genetic basis of HD involves the abnormal expansion of CAG repeats in the huntingtin(HTT)gene,leading to the expansion of a polyglutamine repeat in the HTT protein.Mutant HTT carrying the expanded polyglutamine repeat undergoes misfolding and forms aggregates in the brain,which precipitate selective neuronal loss in specific brain regions.Animal models play an important role in elucidating the pathogenesis of neurodegenerative disorders such as HD and in identifying potential therapeutic targets.Due to the marked species differences between rodents and larger animals,substantial efforts have been directed toward establishing large animal models for HD research.These models are pivotal for advancing the discovery of novel therapeutic targets,enhancing effective drug delivery methods,and improving treatment outcomes.We have explored the advantages of utilizing large animal models,particularly pigs,in previous reviews.Since then,however,significant progress has been made in developing more sophisticated animal models that faithfully replicate the typical pathology of HD.In the current review,we provide a comprehensive overview of large animal models of HD,incorporating recent findings regarding the establishment of HD knock-in(KI)pigs and their genetic therapy.We also explore the utilization of large animal models in HD research,with a focus on sheep,non-human primates(NHPs),and pigs.Our objective is to provide valuable insights into the application of these large animal models for the investigation and treatment of neurodegenerative disorders.

关键词： Huntington's disease Large animal models Sheep Non-human primates Transgenic pigs

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A novel mouse model of PEDF-associated serious liver inflammation,hepatic tumorigenesis and cardiovascular injury mimics human nonalcoholic steatohepatitis

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Genes & Diseases 2024年第1期11卷 11-14页

作者： Xinghui Li Haiping Wang Yandi Wu Li Zou Shijie Dengg Xintu Fu Tongsheng Huang Conghui Shen Teng Wu Weibin Cai guangdong Engineering&Technology Research Center for Disease-Model Animals Laboratory Animal CenterZhongshan School of MedicineSun Yat-sen UniversityGuangzhouGuangdong 510080China Department of Biochemistry Zhongshan School of MedicineSun Yat-sen UniversityGuangzhouGuangdong 510080China School of Pharmacy Guangdong Pharmaceutical UniversityGuangzhouGuangdong 510006China guangdong Provincial Key Laboratory of Digestive Cancer Research The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhenGuangdong 518107China

There are no approvedtherapeuticdrugs for nonalcoholic steatohepatitis(NASH)due to the many bottlenecks,including the lack of preclinical animal models that can perfectly mimic human NASH features,such as systemic metabolic disorders,hepatic steatosis,intense liver inflammation and fibrosis,liver tumorigenesis,and cardiovascularcomplications.i,2"Pigment"epitheliumderived factor(PEDF)is a lipid metabolism regulator with high expression in the liver,and its reduced expression in the liver is closely related to the development of nonalcoholic fatty liver disease(NAFLD).

关键词： inflammation PEDF hepatic

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Prognostic implications of overt congestion in heart failure with preserved ejection fraction and the interaction with spironolactone: Insights from TOPCAT

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中华医学杂志(英文版) 2024年第10期137卷 1249-1251页

作者： Lin Yingwen Zhao Hengli Hu Dongtu Huang Jia Peng You Li Juncong Xu Dingli Zeng Qingchun State Key Laboratory of Organ Failure Research Department of Cardiology Nanfang Hospital Southern Medical University Guangzhou Guangdong China guangdong Provincial Key Laboratory of Clinical Pharmacology Medical Research Institute Guangdong Provincial People’s Hospital Guangdong Academy of Medical Sciences Guangzhou Guangdong China Department of Radiology The Third Affiliated Hospital of Guangzhou Medical University Guangzhou Guangdong China Department of Obstetrics and Gynecology Nanfang Hospital Southern Medical University Guangzhou Guangdong China

Heart failure with preserved ejection fraction (HFpEF) is a clinical entity characterized by impaired diastolic function. Until recently, there have been few studies directly evaluating how volume status impacts future cardiac events for patients with HFpEF. Evidence supporting the application of spironolactone in HFpEF is mainly derived from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. Even though primary analysis of the trial reached a neutral result, subgroup and subsequent post hoc analyses have confirmed its efficacy in selected groups of patients, suggesting that identifying the potential subgroups of patients who would benefit from spironolactone treatment is important.[1] Data regarding the impact of congestion status on the efficacy of spironolactone in HFpEF are lacking. A comprehensive evaluation of volume status could be complicated to some extent. Determining clinically overt congestion by physical signs is expected to be straightforward and practical. Nevertheless, not all physical signs of congestion are present in a patient simultaneously, which necessitates a comprehensive judgment in clinical practice. Latent class analysis (LCA) is a clustering statistical method that can achieve this goal. It has been used to identify potentially distinct subgroups within populations that share certain characteristics. In this study, by leveraging data from the TOPCAT trial, we identified the subgroup of patients with HFpEF with clinically overt congestion by selecting typical signs of congestion for LCA and explored the prognostic implications of baseline overt congestion and time-updated congestive status as well as its interaction with spironolactone treatment.

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