【Objective】 To compare the risk of generalization in patients with ocular myasthenia gravis (OMG) receiving or not receiving immunosuppressive treatment. 【Methods】 The data of patients with OMG registered in Tangdu Hospital of Air Force Military Medical University from January 1, 2015 to May 1, 2019 were reviewed; the patients were divided into treatment group and control group according to whether they had received immunosuppressive treatment. The multivariate Cox proportional hazards regression model analysis was used to compare the risk of generalization between the two groups of patients within 2 years of onset. Sensitivity analysis was used to evaluate the duration of immunosuppressive treatment and the risk of generalization under different immunotherapy regimens. By using stratified analysis, the consistency of the main results across different levels of subgroup factors was evaluated. 【Results】 A total of 702 OMG patients were collected. Of them 367 patients (52.3%) were included in the treatment group, with an average onset age of (50.54±15.1) years, and 159 (43.3%) being female. Another 335 patients (47.7%) were included in the control group, with an average age of (49.1±14.6) years, and 159 ones (47.5%) were female. A total of 28 cases (7.7%) in the treatment group and 106 cases (31.6%) in the control group developed generalization during the observation period. After multivariate-adjusted Cox model analysis, patients who had received immunosuppressive treatment had a significantly lower risk of generalization compared with the control group (HR=0.24; 95% CI: 0.15-0.37; P<0.001). Sensitivity analysis found that the longer the duration of immunosuppression, the lower the risk of generalization (HR=0.88; 95% CI: 0.85-0.91; P<0.001). Stratified analysis showed that immunosuppressive therapy reduced the risk of generalization in different subgroups of patients. 【Conclusion】 Early immunosuppressive treatment can significantly reduce the risk of generalization in patients with OMG.

Background: and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. Methods: This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). Results: Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. Conclusions In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.

Background: and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. Methods: This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). Results: Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. Conclusions In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.

Objective: To explore the relationship between plasma amyloid-β (Aβ) and cognitive decline during 2 year follow-up in a population-based cohort in Xi′an rural areas. Methods: The study was conducted in Qubao village in Xi′an suburbs cognitively normal residents over 40 years old were recruited from October 2014 to March 2015 and given a face-to-face standardized interview. Mini-mental state examination (MMSE) was employed to evaluate the global cognitive function, and quantification of plasma Aβ was measured by sandwich enzyme-linked immunosorbent assay (ELISA) at baseline. Two years later, MMSE was tested at the end of study. Then logistic regression was performed to analyze the relationship between baseline Aβ and cognitive change during 2 year follow-up. Results: A total of 1 020 participants completed the study, among whom 223 subjects (21.9%) presented MMSE scores decline (defined as MMSE scores decreased ≥2 points). Compared with those without decline, participants in the MMSE decline group were older (P<0.001) and had lower education level (P<0.001), while gender, hypertension, hyperlipemia, diabetes mellitus and APOE genotype were not significantly different between two groups. One-way analysis of variance (ANOVA) showed that the MMSE score decline was slighter in the lower tertile of baseline Aβ₁-40 compared with middle tertile (P=0.012), while MMSE decline were similar between different Aβ₁-42 level groups and Aβ_1-42/Aβ_1-40 ratio groups (P=0.758, P=0.671, respectively). Multivariable logistic regression analysis showed that MMSE scores in the lower baseline plasma Aβ_1-40 level declined more slowly (OR=0.565, 95%CI 0.379-0.845, P=0.005). However, the MMSE decline were also similar among different baseline plasma Aβ_1-42 levels groups and Aβ_1-42/Aβ_1-40 ratio groups. Conclusion Population with lower level of baseline plasma Aβ_1-40 manifests lower cognitive decline during 2 years, however further investigation on dynamics of plasma Aβ and long term follow up are needed.

To explore the relationship between plasma amyloid?β (Aβ) and cognitive decline during 2 year follow?up in a population?based cohort in Xi′an rural areas. Methods The study was conducted in Qubao village in Xi′an suburbs cognitively normal residents over 40 years old were recruited from October 2014 to March 2015 and given a face?to?face standardized interview. Mini?mental state examination (MMSE) was employed to evaluate the global cognitive function, and quantification of plasma Aβ was measured by sandwich enzyme?linked immunosorbent assay (ELISA) at baseline. Two years later, MMSE was tested at the end of study. Then logistic regression was performed to analyze the relationship between baseline Aβ and cognitive change during 2 year follow?up. Results A total of 1 020 participants completed the study, among whom 223 subjects (21.9%) presented MMSE scores decline (defined as MMSE scores decreased≥2 points). Compared with those without decline, participants in the MMSE decline group were older (P<0.001) and had lower education level (P<0.001), while gender, hypertension, hyperlipemia, diabetes mellitus and APOE genotype were not significantly different between two groups. One?way analysis of variance (ANOVA) showed that the MMSE score decline was slighter in the lower tertile of baseline Aβ1?40 compared with middle tertile (P=0.012), while MMSE decline were similar between different A β 1?42 level groups and A β 1?42/A β 1?40 ratio groups (P=0.758, P=0.671, respectively). Multivariable logistic regression analysis showed that MMSE scores in the lower baseline plasma A β 1?40 level declined more slowly (OR=0.565, 95%CI 0.379-0.845, P=0.005). However, the MMSE decline were also similar among different baseline plasma Aβ1?42 levels groups and Aβ1?42/Aβ1?40 ratio groups. Conclusion Population with lower level of baseline plasma Aβ1?40 manifests lower cognitive decline during 2 years, however further investigation on dynamics of plasma Aβ and long term follow up are needed.

Objective To investigate the correlation between serum interleukin-6 (IL-6) to albumin ratio (IAR) at admission and early outcome of patients with acute noncardioembolic ischemic stroke.Methods From January 2013 to May 2015,patients with acute noncardioembolic ischemic stroke admitted to the Department of Neurology,the First Affiliated Hospital of Xi'an Jiaotong University were enrolled retrospectively.Three months after onset,the clinical outcome were assessed by the modified Rankin scale (mRS),0-2 was good outcome,and ＞ 2 was poor outcome.The baseline clinical data,laboratory tests,and IAR in both groups were compared.Multivariate logistic regression analysis was used to determine the independent risk factors affecting early outcomes.Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of IAR for early outcome.Results A total of 236 patients were enrolled in the study,including good outcome in 143 (60.6％) and poor outcome in 93 (39.4％).Univariate analysis showed that age (62.99 ± 11.34 years vs.59.62 ± 11.83 years;t =-2.176,P=0.031),serum IL-6 (37.56 ± 3.82 ng/L vs.34.82 ± 3.13 ng/L;t =-6.016,P ＜ 0.001),IAR (1.02 ± 0.08 vs.0.93 ± 0.07;t =-9.474,P＜0.001),and the proportions of patients with severe stroke (6.5％ vs.0％;x2 =8.142,P =0.012) and combined CHD (30.1％ vs.18.2％;x2 =4.542,P =0.033) of the poor outcome group were significantly higher than those of the good outcome group.Multivariate logistic regression analysis showed that high IAR at admission was an independent risk factor for early poor outcome (odds ratio,5.192,95％ confidence interval 3.283-8.213;P ＜0.001).ROC curve analysis showed the optimal cut-off value of IAR predicting for early outcome was 1.00,and the area under the ROC curve was 0.807 (95％ confidence interval 0.748 to 0.860).The sensitivity was 62.4％,the specificity was 88.1％,the positive predictive value was 69.2％,the negative predictive value was 79.3％,and the accuracy was 75.4％.Conclusions High serum IAR at admission was an independent risk factor for early poor outcome in patients with acute noncardioembolic ischemic stroke.It had a certain predictive value for the outcomes.

Objective To explore the characteristics and influencing factors of cognitive dysfunction in patients with essential tremor (ET).Methods We recruited ET patients diagnosed by the Department of Neurology of the First Affiliated Hospital of Xi`an Jiaotong University and healthy volunteers who matched the ET patients in age, gender and education level for the study.We recorded all the patients` demographic information, tremor degree, and family history based on the family tree.All the participants were tested by MMSE, MoCA, ADL, HAMD and HAMA.Results There were 88 ET patients and 63 normal subjects included in the study.According to MMSE, 31.82％ of the patients had cognitive dysfunctions, with orientation, short-term memory, calculation ability, language skills, retelling, reading comprehension, three-level command and drawing being significantly lower than those of the healthy volunteers (P<0.01);orientation was the most serious damage in cognitive function domain (K=0.624, S=0.726);three-level command was the least serious damage (K=0.274, S=0.319).According to MoCA, 86.36％ of the ET patients had cognitive dysfunction higher than normal people (P<0.05);visual space and execution, clock drawing task, naming, attention, 100-7, language skills, abstract thinking and orientation were significantly lower than normal people (P<0.01);the most serious damage in cognitive function domain was visual space and execution (K=0.651, S=0.786); the least serious damage cognitive function domain was “100-7” (K=0.406, S=0.484). Education level and age affected cognitive dysfunction (P<0.05). ADL scores showed negative correlation with cognitive function (correlation =－0.375 and －0.383, respectively; P<0.001). After the effects of anxiety and depression were excluded, onset age and tremor grading were correlated with cognitive dysfunction (P<0.05). When the above factors were put into binary Logistic regression model, education level was found to be contributed to the model (P<0.05).Conclusion Patients with ET widely suffer from cognitive impairment. Age, education level, daily life disability, age of onset, and tremor degree classification can affect cognitive dysfunction.

Objective To investigate the abnormalities of brain gray matter volume in patients with clinically-confirmed essential tremor (ET)of the hands only.Methods We analyzed brain gray matter voxel of 1 7 patients (younger than 55 years)with ET of the hands only and 1 7 healthy controls matched in age,gender and education by optimized voxel-based morphometry (VBM).Results VBM showed marked expansion of the bilateral cerebella, occipital fusiform cortices,and precentral lobes (P uncorrected < 0.005 )in ET patients compared with the controls. Atrophy was only detected in left parietal lobe.We also found volume enlargement in the thalamus,midbrain,and melluda of the left side by region of interest (ROI )analysis (P uncorrected <0.005).Conclusion Patients with arm tremor show expansion of gray matter,which might represent the adaptive reorganizational compensation through the increased demand on the visuospatial control of skilled movements in ET patients with early-stage arm tremor. These morphological changes may help to assess early stage and distinguish subtype of ET.

Objective To investigate the relationship between plasma homocysteine (Hcy) and cognitive impairment so as to provide basis for dementia prevention.Methods Subjects at high risk for stroke were selected from the Screening and Prevention Program of Stroke (organized by the Ministry of Health,from August to December,2012) in Yanta area,Xi' an.Fasting blood was taken from cubital vein to measure Hcy.When Hcy＞ 15 μmol/L was defined as hyperhomocysteinmia,Hcy in the range of 16-30 μ mol/L was considered mild,≥31 μ mol/L as moderate-severe hyperhomocysteinemia.The cognitive function was evaluated by the Mini Mental State Examination (MMSE).MMSE grades under normal value were defined as cognitive impairment.Results 393 subjects were randomly recruited,including 173 men (44.0％) and 220 women (56.0％).Number of cases with cognitive impairment was 70 (17.8％ of the total subjects),with hyperhomocysteinmia was 220 (56.0％ of the total subjects).The prevalence of cognitive impairment did not show significant difference with hyperhomocysteinemia or normal Hcy group (16.8％ vs.19.1％,P ＞ 0.05),neither with mild and moderate-severe hyperhomocysteinemia group (17.0％ vs.16.3％,P＞0.05).Results from Spearman correlation analysis indicated that there was no correlation between MMSE grades and Hcy (rs=-0.01,P=0.85).Prevalence of cognitive impairment in the smoking group was higher than that in the non-smoking group(21.3％ vs.7.8％,P＜0.01),but higher in hypertension group than that in the normal blood pressure group (21.7％ vs.8.0％,P＜0.01).In the stroke group,prevalence of cognitive impairment was seen higher than that in the non-stroke group (25.3％ vs.15.4％,P＜0.05).Based on the results from Binary logistic regression,cognitive impairment appeared to be associated with the levels of education (OR=0.90,95％ CI:0.81-0.98,P=0.02),histories of hypertension (OR=1.02,95％CI:1.01-1.04,P=0.01) and stroke (OR=1.86,95％CI:1.04-3.33,P=0.04),but there was no correlation seen between Hcy and cognitive impairment (OR=0.90,95％ CI:0.51-1.58,P=0.71).Conclusion Plasma homocysteine did not seem a risk factor for cognitive impairment.

The characteristics of virus-like particle (VLP) of JC virus (JCV) as a vector for targeting gene delivery was determined. The exogenous DNA (PUC19) packaged in VLP-Z was resistant to DNase I. VLP-Z was able to deliver a reporter plasmid pEGFP-N1 into HeLa cells and the green fluorescent reporter protein was expressed in these cells. VLP-Z was also able to bind IgG by interaction with the Z fragment of VLP-Z and IgG. These results suggested that VLP-Z might be used as a vector to deliver therapeutic genes to target cells with incorporating IgG antibodies.
Gene Targeting ; methods ; Gene Transfer Techniques ; Genetic Therapy ; methods ; Genetic Vectors ; genetics ; HeLa Cells ; Humans ; Immunoglobulin G ; metabolism ; JC Virus ; genetics ; metabolism ; Virion ; genetics ; metabolism