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Nanomaterials-mediated lysosomal regulation:a robust protein-clearance approach for the treatment of Alzheimer’s disease

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Neural Regeneration Research 2025年第2期20卷 424-439页

作者： Mengqi Hao Jianjian Chu Tinglin Zhang Tong Yin Yuankai Gu Wendanqi Liang Wenbo Ji Jianhua Zhuang Yan Liu Jie Gao You Yin Department of Neurology Second Affiliated Hospital of Naval Medical University(Shanghai Changzheng Hospital)ShanghaiChina School of Health Science and Engineering University of Shanghai for Science and TechnologyShanghaiChina Changhai Clinical Research Unit Shanghai Changhai HospitalNaval Medical UniversityShanghaiChina Department of Clinical Pharmacy Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Neurology Shanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina

Alzheimer’s disease is a debilitating,progressive neurodegenerative disorder characterized by the progressive accumulation of abnormal proteins,including amyloid plaques and intracellular tau tangles,primarily within the ***,crucial intracellular organelles responsible for protein degradation,play a key role in maintaining cellular *** studies have suggested a link between the dysregulation of the lysosomal system and pathogenesis of neurodegenerative diseases,including Alzheimer’s *** the normal physiological function of lysosomes hold the potential to reduce the pathological burden and improve the symptoms of Alzheimer’s ***,the efficacy of drugs in treating Alzheimer’s disease is limited,with major challenges in drug delivery efficiency and ***,nanomaterials have gained widespread use in Alzheimer’s disease drug research owing to their favorable physical and chemical *** review aims to provide a comprehensive overview of recent advances in using nanomaterials(polymeric nanomaterials,nanoemulsions,and carbon-based nanomaterials)to enhance lysosomal function in treating Alzheimer’s *** review also explores new concepts and potential therapeutic strategies for Alzheimer’s disease through the integration of nanomaterials and modulation of lysosomal *** conclusion,this review emphasizes the potential of nanomaterials in modulating lysosomal function to improve the pathological features of Alzheimer’s *** application of nanotechnology to the development of Alzheimer’s disease drugs brings new ideas and approaches for future treatment of this disease.

关键词： Alzheimer’s disease autophagy dysfunction lysosomal acidification lysosomal system nanomaterials neurodegenerative diseases

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Transvaginal natural orifice transluminal endoscopic surgery:A novel gasless technique to hysterectomy

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Laparoscopic, Endoscopic and Robotic Surgery 2022年第1期5卷 35-39页

作者： Suyash naval Shubhada Jajoo Rucha naval Jayashri Rane naval multi speciality hospital M.J.College RoadNear Bhaskar MarketJalgaon 425001India Department of Obstetrics and Gynecology Jawaharlal Nehru Medical CollegeWardha 442107India

Transvaginal natural orifice transluminal endoscopic surgery(vNOTES),as a minimally invasive surgery technique,applies CO_(2) for creating pneumoperitoneum,and uses a closed system to through smoke evacuation from a dedicated outlet or *** has the potential to generate aerosol in the operation room,which can lead to an increased risk of transmission of *** technical note introduces a new technique of gasless pure vNOTES to hysterectomy using silicone face mask as a modified vNOTES port.

关键词： Hysterectomy Natural orifice transluminal endoscopic surgery Transvaginal Gasless

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The functions of exosomes targeting astrocytes and astrocyte-derived exosomes targeting other cell types

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Neural Regeneration Research 2024年第9期19卷 1947-1953页

作者： Hongye Xu He Li Ping Zhang Yuan Gao Hongyu Ma Tianxiang Gao Hanchen Liu Weilong Hua Lei Zhang Xiaoxi Zhang Pengfei Yang Jianmin Liu Neurovascular Center Changhai HospitalNaval Medical UniversityShanghaiChina Department of Emergency Naval Hospital of Eastern TheaterZhoushanZhejiang ProvinceChina

Astrocytes are the most abundant glial cells in the central nervous system;they participate in crucial biological processes,maintain brain structure,and regulate nervous system *** are cell-derived extracellular vesicles containing various bioactive molecules including proteins,peptides,nucleotides,and lipids secreted from their cellular *** evidence shows that exosomes participate in a communication network in the nervous system,in which astrocyte-derived exosomes play important *** this review,we have summarized the effects of exosomes targeting astrocytes and the astrocyte-derived exosomes targeting other cell types in the central nervous *** also discuss the potential research directions of the exosome-based communication network in the nervous *** exosome-based intercellular communication focused on astrocytes is of great significance to the biological and/or pathological processes in different conditions in the *** strategies may be developed for the diagnosis and treatment of neurological disorders by focusing on astrocytes as the central cells and utilizing exosomes as communication mediators.

关键词： astrocytes communication exosomes neurological disorders targeting mechanism

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Reinfection and Risk Factors of SARS-CoV-2 during an Omicron Wave 2022 in Shanghai

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Biomedical and Environmental Sciences 2024年第2期37卷 204-209页

作者： WANG Pei Qin WANG Xiao Hang WANG Jian SHI Zhi Wen CHU Dong Mei WANG Zhi Fei ZHANG Mu Bai LIU Wei ZHOU Zi Jie XIE Wei Fen Department of Gastroenterology Changzheng HospitalNaval Medical UniversityShanghai 200003China Health examination center Changzheng HospitalNaval Medical UniversityShanghai 200003China

multiple waves of coronavirus disease 2019(COVID-19) outbreaks have affected numerous countries worldwide. The first case of SARS-CoV-2 reinfection was reported in Hong Kong in August 2020^([1]), leading to increased interest in the effectiveness of natural immunity acquired from primary infection. While data reports vary across countries, all findings indicate that prior SARS-CoV-2 infection provides substantial protection against reinfection^([2]). However, natural immunity from infection with previous non-Omicron or early Omicron sub-lineages offers lower levels of protection against Omicron reinfection, with rates below 60%^([3]) and approximately 75%[4], respectively.

关键词： immunity infection Omi

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Neoadjuvant radiohormonal therapy for oligo-metastatic prostate cancer:safety and efficacy outcomes from an open-label,dose-escalation,single-center,phase Ⅰ/Ⅱ clinical trial

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Frontiers of Medicine 2023年第2期17卷 231-239页

作者： Yifan Chang Xianzhi Zhao Yutian Xiao Shi Yan Weidong Xu Ye Wang Huojun Zhang Shancheng Ren Department of Urology Shanghai Changhai HospitalNaval Medical UniversityShanghai 200433China Department of Radiation Oncology Shanghai Changhai HospitalNaval Medical UniversityShanghai 200433China Department of Urology Shanghai Changzheng HospitalNaval Medical UniversityShanghai 200003China

To evaluate the safety and efficacy of neoadjuvant radiohormonal therapy for oligometastatic prostate cancer(OMPC),we conducted a 3+3 dose escalation,prospective,phase Ⅰ/Ⅱ,single-arm clinical trial(CHiCTR1900025743),in which long-term neoadjuvant androgen deprivation was adopted 1 month before radiotherapy,comprising intensity modulated radiotherapy to the pelvis,and stereotactic body radiation therapy to all extra-pelvic bone metastases for 4‒7 weeks,at 39.6,45,50.4,and 54 ***-assisted radical prostatectomy was performed after 5‒14 *** primary outcome was treatment-related toxicities and adverse events;secondary outcomes were radiological treatment response,positive surgical margin(pSM),postoperative prostate-specific antigen(PSA),pathological down-grading and tumor regression grade,and survival *** patients were recruited from March 2019 to February 2020,aging 66.2 years in average(range,52‒80).Median baseline PSA was 62.0 ng/*** underwent RARP successfully without open *** patients recorded pathological tumor down-staging(83.3%),and 5(41.7%)with cN1 recorded negative regional lymph nodes on final pathology.66.7%(8/12)recorded tumor regression grading(TRG)–Ⅰ and 25%(3/12)recorded TRG-Ⅱ.Median follow-up was 16.5 *** radiological progression-free survival(RPFS)was 21.3 months,with 2-year RPFS of 83.3%.In all,neoadjuvant radiohormonal therapy is well tolerated for oligometastatic prostate cancer.

关键词： neoadjuvant radiotherapy oligometastatic prostate cancer radical prostatectomy

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Lupenone improves motor dysfunction in spinal cord injury mice through inhibiting the inflammasome activation and pyroptosis in microglia via the nuclear factor kappa B pathway

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Neural Regeneration Research 2024年第8期19卷 1802-1811页

作者： Fudong Li Xiaofei Sun Kaiqiang Sun Fanqi Kong Xin Jiang Qingjie Kong Department of Orthopedics Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Orthopedic Surgery Spine CenterShanghai Changzheng HospitalNaval Medical UniversityShanghaiChina Department of Orthopedic Surgery Naval Medical CenterNaval Medical UniversityShanghaiChina Department of Anesthesiology Shanghai Changzheng HospitalNaval Medical UniversityShanghaiChina

Spinal cord injury-induced motor dysfunction is associated with *** have shown that the triterpenoid lupenone,a natural product found in various plants,has a remarkable anti-inflammatory effect in the context of chronic ***,the effects of lupenone on acute inflammation induced by spinal cord injury remain *** this study,we established an impact-induced mouse model of spinal cord injury,and then treated the injured mice with lupenone(8 mg/kg,twice a day)by intrape ritoneal *** also treated BV2 cells with lipopolysaccharide and adenosine5’-triphosphate to simulate the inflammatory response after spinal cord *** res ults showed that lupenone reduced IKBa activation and p65 nuclear translocation,inhibited NLRP3 inflammasome function by modulating nuclear factor kappa B,and enhanced the conve rsion of proinflammatory M1 mic roglial cells into anti-inflammatory M2 microglial ***,lupenone decreased NLRP3 inflammasome activation,NLRP3-induced mic roglial cell polarization,and microglia pyroptosis by inhibiting the nuclear factor kappa B *** findings suggest that lupenone protects against spinal cord injury by inhibiting inflammasomes.

关键词： inflammasome inflammation lupenone microglia polarization pyroptosis spinal cord injury

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New clinical trial design in precision medicine:discovery,development and direction

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1293-1321页

作者： Xiao-Peng Duan Bao-Dong Qin Xiao-Dong Jiao Ke Liu Zhan Wang Yuan-Sheng Zang Department of Medical Oncology Changzheng HospitalNaval Medical UniversityShanghaiChina

In the era of precision medicine,it has been increasingly recognized that individuals with a certain disease are complex and different from each *** to the underestimation of the significant heterogeneity across participants in traditional"one-sizefits-all"trials,patient-centered trials that could provide optimal therapy customization to individuals with specific biomarkers were developed including the basket,umbrella,and platform trial designs under the master protocol *** recent years,the successive FDA approval of indications based on biomarker-guided master protocol designs has demonstrated that these new clinical trials are ushering in tremendous *** the rapid increase in the number of basket,umbrella,and platform trials,the current clinical and research understanding of these new trial designs,as compared with traditional trial designs,remains *** majority of the research focuses on methodologies,and there is a lack of in-depth insight concerning the underlying biological logic of these new clinical trial ***,we provide this comprehensive review of the discovery and development of basket,umbrella,and platform trials and their underlying logic from the perspective of precision ***,we discuss future directions on the potential development of these new clinical design in view of the"Precision Pro","Dynamic Precision",and"Intelligent Precision".This review would assist trial-related researchers to enhance the innovation and feasibility of clinical trial designs by expounding the underlying logic,which be essential to accelerate the progression of precision medicine.

关键词： clinical approval successive

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Development of preoperative prognostic models including radiological features for survival of singular nodular HCC patients

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Hepatobiliary & Pancreatic Diseases International 2023年第1期22卷 72-80页

作者： Dong-Yang Ding Lei Liu He-Lin Li Xiao-Jie Gan Wen-Bin Ding Fang-Ming Gu Da-Peng Sun Wen Li Ze-Ya Pan Sheng-Xian Yuan Wei-Ping Zhou Third Department of Hepatic Surgery Eastern Hepatobiliary Surgery HospitalNaval Medical UniversityShanghai 200438China Department of Radiodiagnosis Eastern Hepatobiliary Surgery HospitalNaval Medical UniversityShanghai 200438China

Background:Early singular nodular hepatocellular carcinoma(HCC)is an ideal surgical indication in clinical ***,almost half of the patients have tumor recurrence,and there is no reliable prognostic prediction ***,it is unclear whether preoperative neoadjuvant therapy is necessary for patients with early singular nodular HCC and which patient needs *** is critical to identify the patients with high risk of recurrence and to treat these patients preoperatively with neoadjuvant therapy and thus,to improve the outcomes of these *** present study aimed to develop two prognostic models to preoperatively predict the recurrence-free survival(RFS)and overall survival(OS)in patients with singular nodular HCC by integrating the clinical data and radiological ***:We retrospective recruited 211 patients with singular nodular HCC from December 2009 to January 2019 at Eastern Hepatobiliary Surgery hospital(EHBH).They all met the surgical indications and underwent radical *** randomly divided the patients into the training cohort(n=132)and the validation cohort(n=79).We established and validated multivariate Cox proportional hazard models by the preoperative clinicopathologic factors and radiological features for association with RFS and *** analyzing the receiver operating characteristic(ROC)curve,the discrimination accuracy of the models was compared with that of the traditional predictive ***:Our RFS model was based on HBV-DNA score,cirrhosis,tumor diameter and tumor capsule in *** nomogram had fine calibration and discrimination capabilities,with a C-index of 0.74(95%CI:0.68-0.80).The OS nomogram,based on cirrhosis,tumor diameter and tumor capsule in imaging,had fine calibration and discrimination capabilities,with a C-index of 0.81(95%CI:0.74-0.87).The area under the receiver operating characteristic curve(AUC)of our model was larger than that of traditional liver cancer staging system,Korea model and N

关键词： Early-stage hepatocellular carcinoma Singular nodular Radiological features Preoperative prognostic model Recurrence-free survival,Overall survival,Linear equation Neoadjuvant treatment

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The Effect of Acupuncture on Intestinal Motility and Sero－Enzyme Activity in Perioperation

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Chinese Journal of Integrative Medicine 1995年第2期1卷 33-35页

作者： Liu Jian-xin (刘建欣) Zhao Qi (赵琦) Xu De-hua (许德华) Li Zhong-an (李促安) Wang Wei (王炜) Tang Yun (唐云) (naval General hospital, Beijing) (100037) naval General hospital Beijing

The authors studied 39 surgical patients suffering from abdominal illnesses. The patientswere divided into acupuncture and control groups. In the acupuncture group, needles were inserted atacupuncture points Zusanli (St 36) and Sanyinjiao (Sp.6) during the second 12 hours following the opera-tion. The patients were then observed to mark the time of the first passing of flatus. Sero-enzyme activityof glutamic pyruvic transaminase (GPT), glutamic-oxaloacetic transaminase (GOT) and glutamyltranspeptidase ( -GT) was determined before the operation, and measured at two day intervals from the1st to 7th days after the operation. The results show the time of passing flatus in the acupuncture group(58. 78±23. 94 h) was obviously faster than that in the control group (86. 14±20. 43 h) , P

关键词： acupuncture intestinal motility sero-enzyme activity perioperation

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Pathogenic roles of long noncoding RNAs in melanoma: Implications in diagnosis and therapies

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Genes & Diseases 2023年第1期10卷 113-125页

作者： Yuai Xiao Yu Xia Yuchong Wang Chunyu Xue Department of Plastic Surgery Changhai HospitalNaval Medical UniversityShanghai 200433China

Melanoma is one of the most dangerous types of cutaneous neoplasms,which are pigment-producing cells of neuroectodermal origin found all over the body.A great deal of research is focused on the mechanisms of melanoma to promote better diagnostic and treatment options for melanoma in its advanced *** progression of melanoma involves alteration in different levels of gene *** the successful implementation of next-generation sequencing technology,an increasing number of long noncoding RNAs(lncRNAs)sequences have been discovered,and a significant number of them have phenotypic effects in both in vitro and in vivo studies,implying that they play an important role in the occurrence and progression of human cancers,particularly melanoma.A number of evidence indicated that lncRNAs are important regulators in tumor cell proliferation,invasion,apoptosis,immune escape,energy metabolism,drug resistance,epigenetic *** better understand the role of lncRNAs in melanoma tumorigenesis,we categorize melanomaassociated lncRNAs according to their cellular functions and associations with gene expression and signaling pathways in this *** on the mechanisms of lncRNA,we discuss the possibility of lncRNA-target treatments,and the application of liquid biopsies to detect lncRNAs in melanomadiagnosisandprognosis.

关键词： Cellular functions Long noncoding RNAs Melanoma

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