1.Research progress on the pathogenic mechanisms of α-synuclein and related disease models
Yuandong LIN ; Yawen JIANG ; Xiangxing ZHU ; Chunling LU ; Tao WANG ; Yingshan CHEN ; Dongsheng TANG
Acta Laboratorium Animalis Scientia Sinica 2025;33(9):1340-1359
The core pathological feature of Parkinson's disease(PD)is the abnormal aggregation of α-synuclein and the result ing neuronal damage.α-Synuclein exhibits toxic effects when it forms oligomers or fibrils,leading to neuronal death via multiple pathways,including mitochondrial dysfunction,impaired vesicular trafficking,dopamine auto-oxidation,and neuroinflammation.In addition,α-synuclein can propagate between cells via exosomes,endocytosis/exocytosis,tunneling nanotubes,or vagal nerve axonal transport,creating a cascade of pathological effects.Animal models of PD that recapitulate the key pathological hallmark of α-synuclein accumulation are indispensable tools for elucidating disease mechanisms and developing novel therapeutic interventions.To date,various strategies,including transgenic techniques,bacterial artificial chromosome(BAC)-mediated expression,viral vector-mediated overexpression,and gene editing,have been employed to develop α-synuclein overexpression animal models.These models have significantly advanced our exploration of the relationship between PD and α-synuclein.This systematic review considers the structure and function of α-synuclein,its mechanisms of toxicity,intercellular propagation pathways,animal models of overexpression,and potential therapeutic targets based on its pathogenic mechanisms.
2.Research progress on the pathogenic mechanisms of α-synuclein and related disease models
Yuandong LIN ; Yawen JIANG ; Xiangxing ZHU ; Chunling LU ; Tao WANG ; Yingshan CHEN ; Dongsheng TANG
Acta Laboratorium Animalis Scientia Sinica 2025;33(9):1340-1359
The core pathological feature of Parkinson's disease(PD)is the abnormal aggregation of α-synuclein and the result ing neuronal damage.α-Synuclein exhibits toxic effects when it forms oligomers or fibrils,leading to neuronal death via multiple pathways,including mitochondrial dysfunction,impaired vesicular trafficking,dopamine auto-oxidation,and neuroinflammation.In addition,α-synuclein can propagate between cells via exosomes,endocytosis/exocytosis,tunneling nanotubes,or vagal nerve axonal transport,creating a cascade of pathological effects.Animal models of PD that recapitulate the key pathological hallmark of α-synuclein accumulation are indispensable tools for elucidating disease mechanisms and developing novel therapeutic interventions.To date,various strategies,including transgenic techniques,bacterial artificial chromosome(BAC)-mediated expression,viral vector-mediated overexpression,and gene editing,have been employed to develop α-synuclein overexpression animal models.These models have significantly advanced our exploration of the relationship between PD and α-synuclein.This systematic review considers the structure and function of α-synuclein,its mechanisms of toxicity,intercellular propagation pathways,animal models of overexpression,and potential therapeutic targets based on its pathogenic mechanisms.
3.Effects of dexmedetomidine assisted postoperative analgesia on sleep quality in elderly patients after abdominal surgery
Tianhui CHEN ; Yingshan ZHANG ; Jiyuan LI ; Yanjing ZHANG ; Xiaojing LI ; Yiwen ZHANG
The Journal of Clinical Anesthesiology 2024;40(9):928-932
Objective To investigate the effects of dexmedetomidine used to supplement analgesia on sleep quality in elderly patients after abdominal surgery.Methods Ninety-eight elderly patients,56 males and 42 females,aged 65-80 years,BMI 18.5-25.0 kg/m2,ASA physical status Ⅱ or Ⅲ,who un-derwent elective abdominal surgery under general anesthesia were selected and divided into two groups using the random number table method:dexmedetomidine group(group D)and control group(group C),49 pa-tients in each group.The two groups were used the same drugs for induction and maintenance of anesthesia,with different analgesic formulas after surgery.Analgesia formula in group C was sufentanil 2 μg/kg,tropi-setron 4 mg,and normal saline to 100 ml,and in group D was sufentanil 2 μg/kg,dexmedetomidine 5μg/kg,tropisetron 4 mg,and normal saline to 100 ml.In the form of questionnaire survey,consensus sleep diary(CSD)was used to record the patient's sleep latency,number of awakenings and duration of waking after sleep 1 day before surgery and 1 day,3,and 7 days after surgery,and then the actual sleep time and sleep efficiency were calculated.The patient's venous blood was collected at 5:00 to 7:00 in the morning to detect serum melatonin,interleukin-6(IL-6),interleukin-1β(IL-1β)and tumor necrosis factor(TNF-α)concentration.Extubation time,the incidence of cough,agitation,respiratory depression,postoperative bradycardia,nausea and vomiting,lethargy,urinary retention,and other adverse reactions were recorded.Results Compared with group C,the sleep latency was significantly reduced,the actual sleep time and the sleep efficiency were significantly increased 1 day,3,and 7 days after surgery(P<0.05).Compared with group C,the concentration of postoperative melatonin in group D were significantly increased 1 day,3,and 7 days after surgery(P<0.05),the concentration of IL-6,IL-1β and TNF-α in group D were significantly reduced 1 and 3 days after surgery(P<0.05).There was no significant difference in the incidence of ad-verse reactions between the two groups.Conclusion Patient-controlled intravenous analgesia with dexme-detomidine assisted in elderly patients after abdominal surgery can improve sleep efficiency,increase sleep time and postoperative sleep quality,which may be related to the changes of melatonin and inflammatory factors after surgery.
4.Changes in iron content, lipid peroxidation, and ferroptosis-related gene expression in vascular endothelial cells in vitro induced by vibration
Siheng WU ; Qingsong CHEN ; Yingshan ZENG ; Yun XIA ; Hongyu YANG
Journal of Environmental and Occupational Medicine 2024;41(5):560-566
Background Vascular endothelial injury is an important pathogenic step of vibration-induced hand arm vibration disease (HAVD), and long-term vibration exposure can lead to vascular endothelial cell dysfunction and cell damage. Cell ferroptosis may be one of the important mechanisms of vibration-induced vascular endothelial cell injury and HAVD. Objective To explore whether vibration can induce changes in ferroptosis-related indicators in vascular endothelial cells in vitro. Methods Human umbilical vein endothelial cells (HUVEC) were divided into four vibrationgroups and two control groups. The vibration groups were exposed to an vibration setting of 125 Hz, 6.5 m·s−2 frequency band and for different durations: 1 d 2 h (total 1 d, 2 h per day), 1 d 4 h (total 1 d, 4 h per day), 2 d 2 h (total 2 d, 2 h per day), and 2 d 4 h (total 2 d, 4 h per day), respectively. All control groups were treated the same as the experimental groups except no vibration exposure. When the cells were 80% confluent, the control groups and the corresponding experimental groups were harvested at the same time. The effects of subgroup treatments on iron, reduced glutathione (GSH), and malondialdehyde (MDA) in HUVEC were detected with a cell ferrous colorimetric test kit, a reduced GSH colorimetric test kit, and a trace MDA test kit, respectively. Real-time quantitative polymerase chain reaction (RT-PCR) was used to detect the mRNA expressions of ferroptosis-related genes acyl-CoA synthetase long chain family member 4 (ACSL4), tumor protein 53 (P53), recombinant human ferritin heavy chain (FTH1), and glutathione peroxidase 4 (GPX4). Western blot (WB) was used to detect the expression levels of ferroptosis-related proteins in HUVEC. Results Compared with the control groups, the vibration induced an increase in the iron content of HUVEC with a dose-response trend. Compared with the control groups, the reduced GSH content of HUVEC in the vibration group decreased with the increase of vibration time and frequency, and there was a dose-response trend. Compared with the control groups, the intracellular MDA content of HUVEC in the 1 d 2 h, 1 d 4 h, and 2 d 4 h vibration groups increased, and the MDA content in the 1 d 2 h and 1 d 4 h vibration group increased with time. The RT-PCR results showed that the mRNA expression levels of ACSL4 and P53 in the 1 d 4 h group increased compared with the 1 d 2 h group. Compared with the 2 d control group, the mRNA expression levels of ACSL4 in the 2 d 2 h vibration group and the 2 d 4 h vibration group increased, and the mRNA expression level of P53 in the 2 d 4 h vibration group increased. Compared with the 1 d control group, the mRNA expression levels of FTH1 and GPX4 in endothelial cells in the vibration 1 d 2 h group decreased. The WB results showed that compared with the control groups, the expression level of ferroptosis-related protein ACSL4 in endothelial cells increased in the vibration 1 d 2 h group; the expression levels of P53 in the 1 d 2 h and 2 d 4 h vibration groups increased; the expression levels of GPX4 decreased in the 1 d 4 h and 2 d 2 h vibration group, and the decrease was more obvious in the 2 d 2 h vibration group than in the 1 d 2 h vibration group; the above differences were statistically significant (P<0.05). Conclusion Vibration induces an increase in iron content, a decrease in GSH, and an increase in MDA in vascular endothelial cells in vitro, as well as mRNA and protein expressions of ferroptosis-related genes ACSL4, P53, FTH1, and GPX4.
5.Long-term Survivals, Toxicities and the Role of Chemotherapy in Early-Stage Nasopharyngeal Carcinoma Patients Treated with Intensity-Modulated Radiation Therapy: A Retrospective Study with 15-Year Follow-up
Lin WANG ; Jingjing MIAO ; Huageng HUANG ; Boyu CHEN ; Xiao XIAO ; Manyi ZHU ; Yingshan LIANG ; Weiwei XIAO ; Shaomin HUANG ; Yinglin PENG ; Xiaowu DENG ; Xing LV ; Weixiong XIA ; Yanqun XIANG ; Xiang GUO ; Fei HAN ; Chong ZHAO
Cancer Research and Treatment 2022;54(1):118-129
Purpose:
This study was aimed to investigate long-term survivals and toxicities of early-stage nasopharyngeal carcinoma (NPC) in endemic area, evaluating the role of chemotherapy in stage II patients.
Materials and Methods:
Totally 187 patients with newly diagnosed NPC and restaged American Joint Committee on Cancer/ International Union Against Cancer 8th T1-2N0-1M0 were retrospectively recruited. All received intensity-modulated radiotherapy (IMRT)±chemotherapy (CT) from 2001 to 2010.
Results:
With 15.7-year median follow-up, 10-year locoregional recurrence-free survival, distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS) were 93.3%, 93.5%, 92.9% and 88.2%, respectively. Multivariable analyses showed cervical lymph nodes positive and pre-treatment prognostic nutritional index ≥ 52.0 could independently predict DMFS (p=0.036 and p=0.011), DSS (p=0.014 and p=0.026), and OS (p=0.002 and p < 0.001); Charlson comorbidity index < 3 points could predict DSS (p=0.011); age > 45 years (p=0.002) and pre-treatment lactate dehydrogenase ≥ 240 U/L (p < 0.001) predicted OS. No grade 4 late toxicity happened; grade 3 late toxicities included subcutaneous fibrosis (4.3%), deafness or otitis (4.8%), skin dystrophy (2.1%), and xerostomia (1.1%). No differences on survivals were shown between IMRT+CT vs. IMRT alone in stage II patients, even in T2N1M0 (p > 0.05). Unsurprising, patients in IMRT+CT had more acute gastrointestinal reaction, myelosuppression, mucositis, late ear toxicity, and cranial nerve injury (all p < 0.05) than IMRT alone group.
Conclusion
Superior tumor control and satisfying long-term outcomes could be achieved with IMRT in early-stage NPC with mild late toxicities. As CT would bring more toxicities, it should be carefully performed to stage II patients.
6.Study on the epidemic status and risk factors of type 2 diabetes mellitus complicated with nephropathy in Nanchong, Sichuan
Wei ZHANG ; Lirong WANG ; Yu CHEN ; Hang YU ; Dongmei ZHU
Journal of Public Health and Preventive Medicine 2021;32(2):137-140
Objective To explore and analyze the risk factors of type 2 diabetes with kidney disease in Nanchong, Sichuan. Methods A retrospective analysis of 192 cases of type 2diabetic nephropathy (study group) and 224 cases of simple type 2 diabetes (control group) in Nanchong area was conducted. The general data and laboratory test results of the two groups were compared, and logistic regression analysis was used to explore the risk factors. Results In this study, there were a total of 353 patients with type 2diabetes complicated with kidney disease, and the incidence rate was 13.46%. The proportion of smoking and drinking, BMI, fasting blood glucose, glycosylated hemoglobin, total cholesterol, creatinine and blood uric acid in the diabetic nephropathy group were higher than those in the simple diabetes group. The course of disease in the diabetic nephropathy group was longer than that in the simple diabetes group. Course of diabetes, smoking-history, BMI, glycosylated hemoglobin, total cholesterol, and serum uric acid were independent risk factors for type 2 diabetic kidney disease. Conclusion The occurrence and development of diabetic kidney disease is the result of the interaction of multiple factors such as the disease course, smoking, obesity, poor blood glucose control, total cholesterol and serum uric acid. Early detection and control of risk factors can delay the progression of diabetic kidney disease.
7.The correlation between the serum resistin and the collapse process of femoral head necrosis
Xiaoming HE ; Shuidi GONG ; Fengxiang PANG ; Xiaojun CHEN ; Weifeng LI ; Yingshan SHEN ; Lixin CHEN ; Fan YANG ; Shaojun LIU ; Qiushi WEI
The Journal of Practical Medicine 2019;35(4):579-583
Objective We aimed to explor the correlation between the serum resistin levels and the collapse process of femoral head necrosis. Methods Eighty-eight patients with osteonecrosis of the femoral head were included in this study (26, 34 and 28 cases at ARCO stage Ⅱ, Ⅲ and Ⅳ, respectively). Fifty healthy controls were enrolled. The serum resistin levels were detected with ELISA method. We compared the serum resistin levels between the patient group and control group. The differences of serum resistin levels between different ARCO stagesand various disease causes were analyzed in the patient group. Results The resistin levels were significantly higher in patients with osteonecrosis of the femoral than healthy control group (P = 0.026). Compared with control group, the resistin levels significantly increased in patients at ARCO stage Ⅲ and ARCO stage Ⅳ respectively (P = 0.001).The resistin levels of procollapse group (ARCO stage Ⅲ and Ⅳ) were significantly higher than that of precollapse group (ARCO stage Ⅱ) (P = 0.000). There was no statistic difference between ARCO stage Ⅲ andⅣ in resistin levels (P> 0.05). No statistical significance was found between different disease causes. ROC curve analysis of resisrin level indicated theertain accuracy (AUC = 0.749) , sensitivity and significant specificity (77.4%, 61.5%, respectively) in the diagnosis of femoral head necrosis. Conclusions Resistin is closely related to the collapse process of femoral head necrosis. The level of resistin was significantly increased after the collapse of femoral head, which could be useful for the clinical diagnosis of the collapse of femoral head necrosis.
8.Application of bibliometrics and visualization techniques to analyze the global research status and trends of rehabilitation after arthroplasty
Shuidi GONG ; Xiaoming HE ; Xiaolong ZHENG ; Fengxiang PANG ; Weifeng LI ; Lixin CHEN ; Xiaojun CHEN ; Yingshan SHEN ; Fan YANG ; Wei HE ; Shaojun LIU ; Qiushi WEI
Chinese Journal of Orthopaedics 2019;39(3):160-168
Objective To investigate the global research status and trends ofrehabilitation after arthroplasty.Methods The Wed of Science database was used to search the publications on rehabilitation after arthroplasty from 1994 to 2018.The included publish items were statistically analyzed by bibliometrics.VOSviewer software was used to analyze the visual transformation of literature coupling (including author coupling,mechanism coupling and country coupling) and co-occurrence analysis.The research status and trends of rehabilitation after arthrop]asty in recent years were analyzed and predicted.Results A total of 1 702 studies were included in the present study.The number of literatures increased year by year globally,including 612 in the United States as the top number of studies in the world.The total citation frequency (15 433 times) and H index (61) of the research publications were also the highest in the world.China (79 literatures) ranked 6th in the number of global research publications,with total citation frequency (451 times) and H index (12) ranked 14th.The number of publications published by JOURNAL OF ARTHROPLASTY and ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION on rehabilitation after arthroplasty was the highest.The University of Pittsburgh and the University of Toronto were the biggest contributors to publications on rehabilitation after arthroplasty.The theme of rehabilitation after arthroplasty can be divided into five categories:pain management,functional exercise,hospital management,complications and clinical trials.Hospital management wasthe main research field recently and the orthopedic specialty hospital would become a hot research topic in the fulure.Conclusion According to the current global trends,rehabilitation study is deepening and the number of publications will increase continuously.The United States is the largest contributor in this area.The current researches focus on the "hospital management" after arthroplasty.The new type of orthopedic specialty hospital may be the next research hotspot for arthroplasty.
9.The clinical effect of two thrombolytic regimens in patients with arteriovenous fistula embolism
Fengjuan GU ; Yanzi ZHANG ; Xiaolu SUI ; Yunpeng XU ; Aisha ZHANG ; Xun SHEN ; Linghui LIN ; Yingshan LIU ; Jihong CHEN
Journal of Chinese Physician 2018;20(6):847-850
Objective To observe the clinical effect of single urokinase and urokinase pump combined with low-molecular-weight Heparin in the treatment of autogenous arteriovenous fistula thrombolysis,and the influence on inflammatory factors [interleukin (IL)-1,IL-6,tumor necrosis factor-α (TNF-α)] and CD62p.Methods 20 hemodialysis patients hospitalized in our hospital for the treatment of thrombosis in fistula were selected.They were randomly divided into group A (n =10) and group B (n =10).The group A was treated by urokinase infusion,and the group B was treated with urokinase pump combined with low-molecular heparin respectively.Results Compared with that before thrombolysis,the blood flow rate was increased significantly while the IL-1,TNF-oα and CD62p decreased significantly in the two groups after thrombolytic treatment,with statistically significant difference (P < 0.05).Compared with the group A,the IL-1,IL-6 and CD62p in group B were decreased after thrombolytic therapy,with statistically significant difference (P < 0.05).Conclusions Urokinase combined with low-molecular-weight heparin is better than single urokinase in the treatment of arteriovenous fistula thrombolysis,providing a theoretical basis for clinical fistula thrombolysis treatment.
10.Survey on cognitive status quo of nursing staffs on patients safety culture in second-class and tertiary hospitals of Nanchang City
Jingjing ZHANG ; Xia QIAN ; Yuan CHEN ; Guofu HUANG ; Yan LIU ; Ping ZHANG ; Yingshan SHI ; Fengbao XIONG
Chongqing Medicine 2017;46(12):1659-1662,1665
Objective To investigate the current situation of nursing staffs in second-class and tertiary hospitals of Nanchang City and influencing factors in order to provide a basis for the management and research of patients safety.Methods The convenience cluster sampling method was adopted to extract the whole nursing staffs from 7 hospitals(4 second-class hospitals and 3 tertiary hospitals)in Nanchang City as the research subjects.Then the multiple regression method was adopted to analyze the influencing factors of patients safety culture in the second-class and tertiary hospitals of Nanchang City.Results The advantage fields of cognition of the nursing staffs in the second-class hospitals on the patients safety culture were the intra-department teamwork,expectation actions of managers for promoting safety,organizational learning and continuous improvement,feedback and communication of mistakes,while the fields needing to be improved were the communication openness,personnel allocation,non-penalty reactions on mistakes;the advantage fields in the tertiary hospitals were same to those in the second-class hospitals,and the fields needing to be improved included the inter-department cooperation,personnel allocation,non-penalty reactions on mistakes.Conclusion The cognition of nursing staffs in 7 hospitals of Nanchang City on the patients safety culture is in a higher level,but insufficiency still exists,partial fields need to be continuously improved.


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