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Glymphatic system:a gateway for neuroinflammation

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Neural Regeneration Research 2024年第12期19卷 2661-2672页

作者： Kailu Zou Qingwei Deng Hong Zhang Changsheng Huang Department of Anesthesiology Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina xiangya school of medicine Central South UniversityChangshaHunan ProvinceChina National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

The glymphatic system is a relatively recently identified fluid exchange and transpo rt system in the brain.Accumulating evidence indicates thatglymphatic function is impaired not only in central nervous system disorders but also in systemic diseases.Systemic diseases can trigger the inflammatory responses in the central nervous system,occasionally leading to sustained inflammation and functional disturbance of the central nervous system.This review summarizes the current knowledge on the association between glymphatic dysfunction and central nervous system inflammation.In addition,we discuss the hypothesis that disease conditions initially associated with peripheral inflammation ove rwhelm the performance of the glymphatic system,thereby triggering central nervous system dysfun ction,chronic neuroinflammation,and neurodegeneration.Future research investigating the role of the glymphatic system in neuroinflammation may offer innovative therapeutic approaches for central nervous system disorders.

关键词： aquaporin-4 central nervous system disease cerebrospinal fluid chronic neuroinflammation glymphatic dysfunction neurodegeneration peripheral nerve injury perivascular space systemic disease vicious cycle

Research Progress on the Association between Schizophrenia and Toxoplasma gondii Infection

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Biomedical and Environmental Sciences 2024年第6期37卷 647-660页

作者： Yiting Zhu Xiaohui Yang Miaoru Chen Yu Hu Yunfeng Chang Xiang Wu Department of Forensic medicine Science Xiangya School of Basic MedicineCentral South UniversityChangsha 410013HunanChina Nursing Department The Third Xiangya Hospital of Central South UniversityChangsha 410013HunanChina Department of Basic medicine Science Xiangya School of Basic MedicineCentral South UniversityChangsha 410013HunanChina Department of Parasitology Xiangya School of Basic MedicineCentral South UniversityChangsha 410013HunanChina

Toxoplasma gondii(T.gondii or Tg),is an obligatory intracellular parasite with humans as its intermediate hosts.In recent years,significant correlations between T.gondii infection and schizophrenia have been reported,including the possible mediating mechanisms.Currently,mechanisms and hypotheses focus on central neurotransmitters,immunity,neuroinflammation,and epigenetics;however,the exact underlying mechanisms remain unclear.In this article,we review the studies related to T.gondii infection and schizophrenia,particularly the latest research progress.Research on dopamine(DA)and other neurotransmitters,the blood-brain barrier,inflammatory factors,disease heterogeneity,and other confounders is also discussed.In addition,we also summarized the results of some new epidemiological investigations.

关键词： Toxoplasma gondii Schizophrenia Neurotransmitters Neuroinflammation Immunity Epigenetics

Klebsiella pneumoniae infections after liver transplantation:Drug resistance and distribution of pathogens,risk factors,and influence on outcomes

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World Journal of Hepatology 2024年第4期16卷 612-624页

作者： Long Guo Peng Peng Wei-Ting Peng Jie Zhao Qi-Quan Wan Department of Respiratory and Critical Care medicine The Third Xiangya Hospital of Central South UniversityChangsha 410013Hunan ProvinceChina Clinical Laboratory medicine Center Zhuzhou Hospital Affiliated to Xiangya School of MedicineCentral South UniversityZhuzhou 421007Hunan ProvinceChina The Second Affiliated Hospital Class Xiangya School of MedicineCentral South UniversityChangsha 410013Hunan ProvinceChina Department of Liver Surgery Renji HospitalShanghai Jiaotong University School of MedicineShanghai 200127China Department of Transplant Surgery The Third Xiangya Hospital of Central South UniversityChangsha 410013Hunan ProvinceChina Engineering and Technology Research Center for Transplantation medicine of National Health Commission The Third Xiangya Hospital of Central South UniversityChangsha 410013Hunan ProvinceChina

BACKGROUND Liver transplantation(LT)is the only curative treatment for end-stage liver disease.However,LT recipients are susceptible to infection,which is the leading cause of early mortality after LT.Klebsiella pneumoniae infections(KPIs)in the bloodstream are common in LT recipients.We hypothesized that KPIs and carbapenemresistant Klebsiella pneumoniae(CRKP)infections may affect the outcomes of LT recipients.AIM To assess KPI incidence,timing,distribution,drug resistance,and risk factors following LT and its association with outcomes.METHODS This retrospective study included 406 patients undergoing LT at The Third xiangya Hospital of Central South University,a tertiary hospital,from January 2015 to January 2023.We investigated the risk factors for KPIs and assessed the impact of KPIs and CRKP infections on the prognosis of LT recipients using logistic regression analysis.RESULTS KPI incidence was 7.9%(n=32),with lung/thoracic cavity the most frequent site of infection;the median time from LT to KPI onset was 7.5 d.Of 44 Klebsiella pneumoniae isolates,43(97.7%)and 34(77.3%)were susceptible to polymyxin B or ceftazidime/avibactam and tigecycline,respectively;>70%were resistant to piperacillin/tazobactam,ceftazidime,cefepime,aztreonam,meropenem,and levofloxacin.Female sex[odds ratio(OR)=2.827,95%confidence interval(CI):1.256-6.364;P=0.012],pre-LT diabetes(OR=2.794,95%CI:1.070-7.294;P=0.036),day 1 post-LT alanine aminotransferase(ALT)levels≥1500 U/L(OR=3.645,95%CI:1.671-7.950;P=0.001),and post-LT urethral catheter duration over 4 d(OR=2.266,95%CI:1.016-5.054;P=0.046)were risk factors for KPI.CRKP infections,but not KPIs,were risk factors for 6-month all-cause mortality post-LT.CONCLUSION KPIs occur frequently and rapidly after LT.Risk factors include female sex,pre-LT diabetes,increased post-LT ALT levels,and urethral catheter duration.CRKP infections,and not KPIs,affect mortality.

关键词： Liver transplantation Klebsiella pneumoniae infections Carbapenem-resistant Klebsiella pneumoniae Risk factors Outcomes

Role of adhesion molecules in cancer and targeted therapy

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Science China(Life Sciences) 2024年第5期67卷 940-957页

作者： Chunmei Fan Fang Xiong Shanshan Zhang Zhaojian Gong Qianjin Liao Guiyuan Li Can Guo Wei Xiong He Huang Zhaoyang Zeng NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha 410000China Department of Histology and Embryology Xiangya School of MedicineCentral South UniversityChangsha410013China Department of Stomatology Xiangya HospitalCentral South UniversityChangsha 410078China Department of Oral and Maxillofacial Surgery The Second Xiangya HospitalCentral South UniversityChangsha 410011China Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education Cancer Research InstituteCentral South UniversityChangsha 410078China

Adhesion molecules mediate cell-to-cell and cell-to-extracellular matrix interactions and transmit mechanical and chemical signals among them.Various mechanisms deregulate adhesion molecules in cancer,enabling tumor cells to proliferate without restraint,invade through tissue boundaries,escape from immune surveillance,and survive in the tumor microenvironment.Recent studies have revealed that adhesion molecules also drive angiogenesis,reshape metabolism,and are involved in stem cell self-renewal.In this review,we summarize the functions and mechanisms of adhesion molecules in cancer and the tumor microenvironment,as well as the therapeutic strategies targeting adhesion molecules.These studies have implications for furthering our understanding of adhesion molecules in cancer and providing a paradigm for exploring novel therapeutic approaches.

关键词： adhesion molecules tumor microenvironment invasion and metastasis reshaping metabolism angiogenesis immune evasion tumor stemness therapeutic strategy

Multifunctional nanoparticle-mediated combining therapy for human diseases

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Signal Transduction and Targeted Therapy 2024年第2期9卷 343-375页

作者： Xiaotong Li Xiuju Peng Makhloufi Zoulikha George Frimpong Boafo Kosheli Thapa Magar Yanmin Ju Wei He school of Pharmacy China Pharmaceutical UniversityNanjing 2111198PR China xiangya school of Pharmaceutical Sciences Central South UniversityChangsha 410013PR China Shanghai Skin Disease Hospital Tongji University School of MedicineShanghai 200443China

Combining existing drug therapy is essential in developing new therapeutic agents in disease prevention and treatment.In preclinical investigations,combined effect of certain known drugs has been well established in treating extensive human diseases.Attributed to synergistic effects by targeting various disease pathways and advantages,such as reduced administration dose,decreased toxicity,and alleviated drug resistance,combinatorial treatment is now being pursued by delivering therapeutic agents to combat major clinical illnesses,such as cancer,atherosclerosis,pulmonary hypertension,myocarditis,rheumatoid arthritis,inflammatory bowel disease,metabolic disorders and neurodegenerative diseases.Combinatorial therapy involves combining or co-delivering two or more drugs for treating a specific disease.Nanoparticle(NP)-mediated drug delivery systems,i.e.,liposomal NPs,polymeric NPs and nanocrystals,are of great interest in combinatorial therapy for a wide range of disorders due to targeted drug delivery,extended drug release,and higher drug stability to avoid rapid clearance at infected areas.This review summarizes various targets of diseases,preclinical or clinically approved drug combinations and the development of multifunctional NPs for combining therapy and emphasizes combinatorial therapeutic strategies based on drug delivery for treating severe clinical diseases.Ultimately,we discuss the challenging of developing NP-codelivery and translation and provide potential approaches to address the limitations.This review offers a comprehensive overview for recent cutting-edge and challenging in developing NP-mediated combination therapy for human diseases.

关键词： drugs diseases prevention

Left lower lobe sleeve resection for the clear cell variant of pulmonary mucoepidermoid carcinoma:A case report

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World Journal of Clinical Cases 2024年第8期12卷 1422-1429页

作者： Xiao-Hui Yu Wen-Xiang Wang De-Song Yang Liang-Hui Gong Department of Pathology Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha 410031Hunan ProvinceChina The Second Department of Thoracic Surgery Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha 410031Hunan ProvinceChina

BACKGROUND Pulmonary mucoepidermoid carcinoma(PMEC)is a rare malignancy that arises from minor salivary glands within the tracheobronchial tree.The clear cell variant of PMEC is exceptionally uncommon and presents notable diagnostic challenges,primarily attributable to its morphological similarity to other tumors containing clear cells.CASE SUMMARY A 22-year-old male,formerly in good health,came in with a two-month duration of persistent cough and production of sputum.Subsequent imaging and bronchoscopy examinations revealed a 2 cm tumor in the distal left main bronchus,which resulted in complete atelectasis of the left lung.Further assessment via positron emission tomography/computed tomography scans and endoscopic biopsy confirmed the primary malignant nature of the tumor,charac-terized by clear cell morphology in most of the tumor cells.The patient underwent a left lower lobe sleeve resection accompanied by systematic mediastinal lymph node dissection.Molecular pathology analysis subsequently revealed a CRTC3-MAML2 gene fusion,leading to a definitive pathological diagnosis of the clear cell variant of PMEC,staged as T2N0M0.After surgery,the patient experienced a smooth recovery and exhibited no signs of recurrence during the one-and-a-half-year follow-up period.CONCLUSION This article describes an unusual case of a clear cell variant of PMEC characterized by the presence of a CRTC3-MAML2 gene fusion in a 22-year-old male.The patient underwent successful left lower lobe sleeve resection.This case underscores the distinctive challenges associated with diagnosing and treating this uncommon malignancy,underscoring the importance of precise diagnosis and personalized treatment strategies.

关键词： Pulmonary mucoepidermoid carcinoma Clear cell variant CRTC3-MAML2 gene fusion Sleeve lobectomy Case report

Clinical effect of laparoscopic radical resection of colorectal cancer based on propensity score matching

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World Journal of Gastrointestinal Surgery 2024年第1期16卷 124-133页

作者： Yang Liu Xian-Xue Wang Yu-Lin Li Wen-Tao He Hong Li Hua Chen Department of General Surgery Changde HospitalXiangya School of MedicineCentral South University(The First People’s Hospital of Changde City)Changde 415000Hunan ProvinceChina Department of Anesthesiology Changde HospitalXiangya School of MedicineCentral South University(The First People’s Hospital of Changde City)Changde 415000Hunan ProvinceChina

BACKGROUND The incidence of colorectal cancer(CRC)is increasing annually.Laparoscopic radical resection of CRC is a minimally invasive procedure preferred in clinical practice.AIM To investigate the clinical effect of laparoscopic radical resection of CRC on the basis of propensity score matching(PSM).METHODS The clinical data of 100 patients who received inpatient treatment for CRC at Changde Hospital,xiangya school of medicine,Central South University(The First People’s Hospital of Changde City)were analyzed retrospectively.The control group included patients who underwent open surgery(n=43),and those who underwent laparoscopic surgery formed the observation group(n=57).The baseline information of both groups was equipoised using 1×1 PSM.Differences in the perioperative parameters,inflammatory response,immune function,degree of pain,and physical status between the groups were analyzed.RESULTS Thirty patients from both groups were successfully matched.After PSM,baseline data showed no statistically significant differences between the groups:(1)Periop-erative parameters:The observation group had a longer surgery time,less intra-operative blood loss,earlier first ambulation and first anal exhaust times,and shorter gastric tube indwelling time than the control group;(2)Inflammatory response:24 h after surgery,the levels of interleukin-6(IL-6),C-reactive protein(CRP),and tumor necrosis factor-α(TNF-α)between groups were higher than preoperatively.IL-6,CRP,and TNF-αlevels in the observation group were lower than in the control group;(3)Immune function:At 24 h after surgery,counts of CD4-positive T-lymphocytes(CD4+)and CD4+/CD8-positive T-lymphocytes(CD8+)in both groups were lower than those before surgery,whereas CD8+was higher than that before surgery.At 24 h after surgery,both CD4+counts and CD4+/CD8+in the observation group were higher than those in the control group,whereas CD8+counts were lower;(4)Degree of pain:The visual analog scale scores in the observation group were lower than those in the control group at

关键词： Colorectal cancer Laparoscopic Open surgery Inflammatory reaction Immune function Propensity score

Extracellular vesicles from human urine-derived stem cells delay aging through the transfer of PLAU and TIMP1

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1166-1186页

作者： Shanshan Rao Zehui He Zun Wang Hao Yin Xiongke Hu Yijuan Tan Tengfei Wan Hao Zhu Yi Luo Xin Wang Hongming Li Zhenxing Wang Xinyue Hu Chungu Hong Yiyi Wang Mingjie Luo Wei Du Yuxuan Qian Siyuan Tang Hui Xie Chunyuan Chen Department of Orthopedics Movement System Injury and Repair Research CenterXiangya HospitalCentral South UniversityChangsha 410008China Hunan Key Laboratory of Angmedicine Changsha 410008China xiangya school of Nursing Central South UniversityChangsha 410013China Department of Pediatric Orthopedics Hunan Children’s HospitalUniversity of South ChinaChangsha 410007China Department of Respiratory medicine Xiangya HospitalCentral South UniversityChangsha 410008China school of Nursing Xinjiang Medical UniversityUrumqiXinjiang 830000China Department of Rehabilitation Xiangya HospitalCentral South UniversityChangsha 410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangsha 410008China

Aging increases the risks of various diseases and the vulnerability to death.Cellular senescence is a hallmark of aging that contributes greatly to aging and aging-related diseases.This study demonstrates that extracellular vesicles from human urine-derived stem cells(USC-EVs)efficiently inhibit cellular senescence in vitro and in vivo.The intravenous injection of USC-EVs improves cognitive function,increases physical fitness and bone quality,and alleviates aging-related structural changes in different organs of senescence-accelerated mice and natural aging mice.The anti-aging effects of USC-EVs are not obviously affected by the USC donors’ages,genders,or health status.Proteomic analysis reveals that USC-EVs are enriched with plasminogen activator urokinase(PLAU)and tissue inhibitor of metalloproteinases 1(TIMP1).These two proteins contribute importantly to the anti-senescent effects of USC-EVs associated with the inhibition of matrix metalloproteinases,cyclin-dependent kinase inhibitor 2A(P16INK4a),and cyclin-dependent kinase inhibitor 1A(P21cip1).These findings suggest a great potential of autologous USC-EVs as a promising anti-aging agent by transferring PLAU and TIMP1 proteins.

关键词： Extracellular vesicles Urine-derived stem cells Cellular senescence Anti-aging PLAU TIMP1 Senescence-accelerated mice Natural aging mice

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Bone Research 2024年第1期12卷 122-136页

作者： Nan-Yu Zou Ran Liu Mei Huang Yu-Rui Jiao Jie Wei Yangzi Jiang Wen-Zhen He Min Huang Yi-Li Xu Ling Liu Yu-Chen Sun Mi Yang Qi Guo Yan Huang Tian Su Ye Xiao Wei-Shan Wang Chao Zeng Guang-Hua Lei Xiang-Hang Luo Chang-Jun Li Department of Endocrinology Endocrinology Research CenterXiangya Hospital of Central South UniversityChangshaHunan 410008China Department of Orthopaedics Xiangya Hospital of Central South UniversityChangshaHunan 410008China Department of Epidemiology and Health Statistics Xiangya School of Public HealthCentral South UniversityChangshaChina Hunan Key Laboratory of Joint Degeneration and Injury ChangshaHunan 410008China Key Laboratory of Aging-related Bone and Joint Diseases Prevention and Treatment Ministry of EducationXiangya HospitalCentral South UniversityChangshaChina school of Biomedical Sciences Institute for Tissue Engineering and Regenerative MedicineFaculty of MedicineThe Chinese University of Hong KongHong Kong SARChina Department of Orthopaedics The First Affiliated Hospital of Shihezi UniversityShiheziXinjiangChina National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan 410008China

Skeletal stem/progenitor cell(SSPC)senescence is a major cause of decreased bone regenerative potential with aging,but the causes of SSPC senescence remain unclear.In this study,we revealed that macrophages in calluses secrete prosenescent factors,including grancalcin(GCA),during aging,which triggers SSPC senescence and impairs fracture healing.Local injection of human rGCA in young mice induced SSPC senescence and delayed fracture repair.Genetic deletion of Gca in monocytes/macrophages was sufficient to rejuvenate fracture repair in aged mice and alleviate SSPC senescence.Mechanistically,GCA binds to the plexin-B2 receptor and activates Arg2-mediated mitochondrial dysfunction,resulting in cellular senescence.Depletion of Plxnb2 in SSPCs impaired fracture healing.Administration of GCA-neutralizing antibody enhanced fracture healing in aged mice.Thus,our study revealed that senescent macrophages within calluses secrete GCA to trigger SSPC secondary senescence,and GCA neutralization represents a promising therapy for nonunion or delayed union in elderly individuals.

关键词： healing union senescence