1.Effects of Mitochondrial Unfolded-Protein Response on Aggregation Toxicity of Amyloid-β Protein
Qiong PENG ; Sixu ZHAO ; Wenjuan DENG ; Ziyuan ZHONG ; Weizhang JIA
Journal of Sun Yat-sen University(Medical Sciences) 2017;38(4):481-488
[Objective] To investigate the effects of mitochondrial unfolded-protein response (UPRmt) on the aggregation toxicity of Aβ protein in Alzheimer's disease (AD).[Methods] By cloning the mitochondrial outer membrane tomm-22,inner membrane E04A4.5 and atfs-1 genes of Caenorhabditis elegans (C.elegans) and constructing the L4440 interference vectors,HT115 competent cells were transformed to prepare tomm-22,E04A4.5 and atfs-1 RNAi bacteria.The effects of tomm-22 and E04A4.5 RNAi on the process of paralysis were investigated through transgenic AD disease models CL4176 and CL2006.The life span of wild type N2 C.elegans was observed after RNAi of tomm-22 and E04A4.5.The regulatory role of ATFS-1 signaling by atfs-1 RNAi in inhibition of Aβ protein aggregation was detected.The dynamic changes of UPRmt in transgenic SJ4100 nematode and the autophagy level in transgenic DA2123 nematodes were analyzed by tomm-22 and E04A4.5 RNAi.[Results] We successfully established the UPRmt model by cloning mitochondrial tomm-22 and E04A4.5 of C.elegans and further constructing RNAi bacteria,and showed that they can suppress aggregation toxicity of Amyloid-β (Aβ) protein in AD model CL4176,and slow down paralysis process.The life span of wild type N2 was significantly shortened after feeding with the tomm-22 and E04A4.5 RNAi bacteria.At the same time,the progressive paralysis AD model CL2006 shows a delayed paralysis in the early stage of life cycle but get acceleration in the late.These results illustrate that the UPRmt can alleviate the mitochondrial stress and improve the function of mitochondria at least in the short term.The atfs-1 RNAi confirmed that delayed paralysis process of AD model CL4176 is not directly related to the ATFS-1 signal.However,tomm-22 and E04A4.5 RNAi can gradually increase the UPRmt response and induce the expression level of autophagy-related molecules LGG-1,suggesting that tomm-22 and E04A4.5 RNAi may play a role in delaying the AD disease process by enhancing the activity of autophagy in C.elegans.[Conclusions] The study found that the UPRmt can inhibit the accumulation of A β protein by coordinating the signal transduction between mitochondria and nucleus,and can help to restore mitochondria and even intracellular protein homeostasis for protecting the normal physiological function of cells,and also provides new targets for prevention and treatment of neurodegenerative diseases such as AD.
2.Perioperative complications of stenting with symptomatic intracranial artery stenosis
Zhugui QIN ; Weizhang ZHONG ; Yuan CHEN ; Binglin FAN ; Jidong XIAO ; Cuifang LIAO
The Journal of Practical Medicine 2017;33(18):3030-3034
Objective To investigate the perioperative complications of stenting with symptomatic intracra-nial artery stenosis and study the mechanism and prevention of complications. Methods 63 patients were collect-ed from Stroke Center of Guangxi. They were proved intracranial artery stenosis and performed intracranial stents. Patients′ age,with hypertension,diabetes and hyperlipidemia or not,smoking or not,types and occurrence time of complications were registered. Results 63 patients were registered and 2 patients terminated operation due to blood vessels circuity or serious vessel spasm. Operation success rate reached 96.83%. 5 patients had complications among 63 cases,with complication incidence of 8.20%. 3 patients experienced cerebral hemorrhage and two cere-bral infarction in peri-operation period. 2 patients died of complications and mortality rate was 3.28%. Conclu-sions The incidence rate of complications of intracranial stenting with symptomatic intracranial artery stenosis is relatively high and it can be reduced by preoperative sufficient assessment and prudent selection ,careful operation and strict management after operation.
3.Influence of classification of psychological guidance on anxiety and pain in endovascular interventional treatment of patients with cerebrovascular stenosis disease
Juandai CHEN ; Guifen FU ; Huiwen HUANG ; Caihong ZHANG ; Weizhang ZHONG
Chinese Journal of Modern Nursing 2017;23(25):3212-3215
Objective To discuss the effects of the classification of psychological guidance on the emotion and prognosis of patients with cerebrovascular stenosis disease undergoing intravascular interventional therapy and to investigate effective interventions.Methods A total of 101 patients with cerebrovascular stenosis disease who underwent intravascular interventional treatment from June 2014 to September 2016 were selected and divided into experimental group (n=52) and control group (n=49) using random number method. Patients in the control group accepted conventional preoperative education instruction, while patients in the experimental group received additional postoperative classified psychological guidance. The Hamilton Anxiety Scale (HAMA), pain scores, postoperative blood pressure changes and adverse reactions were compared between the two groups before and after surgery.Results The number of preoperative patients who were not anxiety, possible anxiety and anxiety were 5, 20, and 27 respectively in the experimental group, and were 3, 19, and 27 in the control group. There was no statistic difference between two groups (Z=0.444,P=0.657). The number of postoperative patients who were not anxiety, possible anxiety and anxiety were 29, 17, and 6 respectively in the experimental group, and were 14, 24, and 11 in the control group. There was a statistically significant difference between two groups (Z=2.710,P=0.007). There were significant differences in pain score, blood pressure, dysuria and insomnia between the two groups after operation (P<0.05).Conclusions The classification of psychological guidance can effectively stabilize the patients' psychology and emotion who underwent the cerebral vascular interventional operation, relieve the pain, help to control the blood pressure, reduce complications and adverse reactions, and improve the prognosis of patients.
4.The analysis on the risk factors of infection after cerebral infarction
Binglin FAN ; Lvli LI ; Junjie WEI ; Weizhang ZHONG ; Zhi CHEN ; Yanhua LI
Chinese Journal of Nervous and Mental Diseases 2017;43(11):651-655
Objective To explore the risk factors of poststroke infection after cerebral infarction. Methods We consecutively included 283 patients with acute ischemic infarcts confirmed by diffusion-weighted imaging (DWI) within 72 hours from Guangxi stroke center. Based on infection status, patients were divided into Not infection group(n=198) and infection group (n=85). The serum cortisol and plasma IL-4 were assessed using chemiluminescent system and double antibody sandwich enzyme linked immunosorbent assay at admission and seventh day later,respectively. Results Compare to no infection group, smoking, mechanical ventilation, diabetes mellitus, dysphagia, COPD,level of consciousness, cortisol and IL-4 at admission, NIHSS, middle area and large area infarction, large atherosclerosis and cardiogenic infarction, left side,both side and subtentorial infarction are more liable to infection(P<0.05);After a Single-factor and Multivariate analysis,we found that cortisol(OR 3.26)and IL-4(OR 2.83)at admission,large area infarction(OR 2.67),left side(OR 3.78)and subtentorial infarction(OR 3.12)were significant correlated with infection, suggesting that they might be the independent risk factors for infection after cerebral infarction. Conclusion Immunological factors and different regional cerebral infarction may increase susceptibility to infection after stroke.