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This pilot study was intended to evaluate the effects of active game play on cognition, quality of life, and depression for older people with dementia.Thirty-eight older people with dementia were recruited. Eighteen people received eight-week active game play using Xbox 360 Kinect. Twenty people received their usual care. The Mini Mental State Examination, Quality of Life-Alzheimer's Disease and Cornell Scale for Depression in Dementia were used to measure the outcomes.The results showed that there was no significant improvement on the mean scores of Mini Mental State Examination (The study demonstrated that the active game play was effective in improving quality of life and alleviating depression in older people with dementia.Findings highlight the potential for gaming as a non-pharmacological interventions for older people with dementia.

Alzheimer disease (AD) is the most common neurodegenerative disease of the central nervous system. The stability of the telomere-telomerase system is closely related to AD. A previous meta-analysis indicated that AD patients had shorter telomere length (TL) than control subjects. However, there are no consistent telomerase activity findings in AD patients, and the published telomerase studies were not meta-analyzed yet.We searched all the related studies that probed into TL and/or telomerase activity in AD patients based on PubMed and Embase database from the establishment to September 2020. The Chinese National Knowledge Infrastructure, Wanfang and China Science and Technology Journal Database were also utilized. The quality of the included studies was evaluated by using Newcastle-Ottawa Scale. All the statistical analyses of this meta-analysis were performed using Stata version 15.0.Analyzing 30 TL data from 2248 AD patients and 4865 controls, AD patients had a significantly shorter TL than the controls, with a standardized mean difference of -0.70 (confidence interval: -0.95 to -0.46; P0.05). The meta-analysis included 3 primary studies and did not find a significant difference in the telomerase activity between 233 AD patients and 132 controls, but AD patients had a trend of increased telomerase activity compared with controls (standardized mean difference: 0.47; confidence interval: -0.29 to 1.23; P0.05).Our results showed that compared with the control group, the AD group had a shorter TL and may have higher telomerase activity.

OBJECTIVE The antenatal screening strategy remains inadequate for eliminating congenital syphilis. To further eliminate maternal fetal transmission, preconception syphilis screening is considered an option. In this study, we investigated syphilis seropositivity and intra-couple discordance among married couples planning a pregnancy in China to provide essential baseline evidence for preconception syphilis screening. DESIGN Population-based survey. SETTING National preconception registered data. POPULATION Married Chinese couples planning conception within 6 months between 2013 and 2018. METHODS Syphilis was screened using rapid plasma reagin (RPR); infection self-reporting and sociodemographic characteristics were collected through questionnaires and medical records, respectively. r 3.2.2 and arcgis 10.2 were used for statistical analyses and geographic mapping. MAIN OUTCOME MEASURES RPR seropositivity. RESULTS Among 31 955 041 couples, 29 737 172 (93.06%) had complete RPR results for both spouses; of those, 0.62% (186 100) were seropositive, with dramatic intra-couple discordance, with 0.33% positivity in wives, 0.24% positivity in husbands and 0.05% positivity in both spouses. Across time, both seropositivity and intra-couple discordance remained stable. Seropositivity in different regions varied significantly, with provincial rates ranging geographically from Tibet (0.8%) to Hebei (0.2%) (P

Background By comparing the detection rate and type of targeted gene mutations in non-small cell lung cancer (NSCLC) between amplification refractory mutation system PCR (ARMS-PCR) and next-generation sequencing (NGS), the characteristics and application advantages of non-small cell lung cancer detection are explained, providing a basis for clinicians to effectively select the corresponding detection methods. Methods and materials The cases of targeted genes for lung cancer were selected from the First Affiliated Hospital of Chongqing Medical University from January 2016 to October 2020. A sample of 4467 cases was selected, and they were diagnosed with NSCLC by Pathological biopsy. Sample sources include surgical resection, bronchoscope biopsy, metastatic biopsy, blood, sputum, cytology of pleural effusion. Among them, 3665 cases were detected by ARMS-PCR technique, and 802 cases were detected by NGS technology. The detection rate and type of ARMS-PCR and NGS techniques for EGFR gene mutations (including exon 18, exon 19, exon 20, exon 21 and so on) in different NSCLC samples were compared, respectively. Results The total mutation rate of EGFR gene detected by ARMS-PCR was 47.6% while 42.4% detected by NGS which indicated that there was a significant difference between the two methods in detecting total mutation of EGFR gene (P Conclusion It showed that NGS could direct the drug use for the resistant patients. However, some rare loci could be detected by NGS but the importance and directed meaning are still unknown and the number of rare mutations is rare too. Further research on new biomarkers and technique is still needed for early diagnosis, directing drug use and assessing the therapy prognosis.

Introduction Chronic vertebral basilar artery occlusion is one of the most common causes of ischemic stroke, which accounts for roughly 20% of all cases. However, the evidence for the precise clinical effect in treatment of the initial segment of chronic vertebral basilar artery occlusion is not sufficient. Aim To evaluate the feasibility and efficacy of endovascular therapy in the initial segment of chronic vertebral basilar artery occlusion. Material and methods This is a retrospective study based on data obtained from Lishui Hospital of Zhejiang University. We identified patients who underwent treatment for initial segment occlusion of the vertebral basilar artery from September 2014 to September 2018. Results Among a total of twenty-two subjects, 77.27% of them were men and the median age was 61 years old. The primary medical history of these patients included hypertension (15, 68.18%), hyperlipidemia (13, 59.09%), diabetes mellitus (11, 50.00%), and coronary artery disease (6, 27.27%). About 54.54% of the patients were current smokers. Successful recanalization was achieved in 86.36% of patients. Five cases of balloon dilatation were recanalized and fourteen cases were treated by balloon dilation combined with stent implantation. During the follow-up period, there were no recurrent cerebral ischemic events, including transient ischemic attack or stroke. Six (27.27%) arteries were found to exhibit angiographic re-stenosis. Conclusions The clinical effect of balloon dilatation or balloon dilatation combined with stenting in the treatment of chronic vertebral basilar artery occlusion in the beginning segment was feasible and safe.

Creatine kinase is a muscle enzyme that has been reported at various levels in different studies involving patients with amyotrophic lateral sclerosis. In the present retrospective case-control study, we included 582 patients with amyotrophic lateral sclerosis and 582 age- and sex-matched healthy controls. All amyotrophic lateral sclerosis participants received treatment in the Department of Neurology, West China Hospital, China, between May 2008 and December 2018. Serum creatine kinase levels in patients with amyotrophic lateral sclerosis were significantly higher than those in healthy controls. Subgroup analysis revealed that serum creatine kinase levels in men were higher than those in women in both amyotrophic lateral sclerosis patients and healthy controls. Compared with patients with bulbar-onset amyotrophic lateral sclerosis, patients with limb-onset amyotrophic lateral sclerosis had higher creatine kinase levels. Spearman’s correlation analysis revealed that serum creatine kinase levels were not correlated with body mass index, Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised score, or progression rate. After adjusting for prognostic covariates, higher log creatine kinase values were correlated with higher overall survival in the amyotrophic lateral sclerosis patients. We also investigated the longitudinal changes in serum creatine kinase levels in 81 amyotrophic lateral sclerosis patients; serum creatine kinase levels were decreased at the second blood test, which was sampled at least 6 months after the first blood test. Together, our results suggest that serum creatine kinase levels can be used as an independent factor for predicting the prognosis of amyotrophic lateral sclerosis patients. This study received ethical approval from the Ethics Committee of West China Hospital, China (approval No. 2015(236)) on December 23, 2015.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the death of motor neurons. A fundamental pathogenesis of ALS is the prolonged cell stress in neurons, which is caused by either accumulation of protein aggregates or reactive oxygen species. However, the mechanistic link between stress sensing and cell death is unsettled. Here, we identify that miR‐183‐5p, a neuron‐enriched miRNA, couples stress sensing and cell death programming in ALS. miR‐183‐5p is immediately induced by hydrogen peroxide, tunicamycin or TNF‐α in neurons. The overexpression of miR‐183‐5p increases neuron survival under stress conditions, whereas its knockdown causes neuron death. miR‐183‐5p coordinates apoptosis and necroptosis pathways by directly targeting PDCD4 and RIPK3, and thus protects neurons against cell death under stress conditions. The consistent reduction of miR‐183‐5p in ALS patients and mouse models enhances the notion that miR‐183‐5p is a central regulator of motor neuron survival under stress conditions. Our study supplements current understanding of the mechanistic link between cell stress and death/survival, and provides novel targets for clinical interventions of ALS.

Purpose: Atherosclerosis causes plaque to build-up in arteries. Effect of the specific local hemodynamic environment around an atherosclerotic plaque on the thrombosis formation does not remain quite clear but is believed to be crucial. The aim of this study is to uncover the flow effects on plaques formation. Methods: To study the mechanically regulated plaque formation, the flow fields in artery blood vessels with different stenosis rates at various Reynolds numbers were simulated numerically with the two-dimensional axisymmetric models, and the hemodynamic characteristics around the plaque were scaled with stenosis rate and Reynolds number. Results: The results showed that increases of both Reynolds number and stenosis rate facilitated the occurrence of flow separation phenomenon, extended recirculation zone, and upregulated the maximum normalized wall shear stress near the plaque throat section while downregulated the minimal normalized wall shear stress at the front shoulder of plaque, as it should be; in the atherosclerotic plaque leeside of the recirculation zone, an obvious catch bond region of wall shear stress might exist especially under low Reynolds number with stenosis rate smaller than 30%. This catch bond region in the plaque leeside might be responsible for the LBF (low blood flow)-enhanced formation of the atherosclerotic plaque. Conclusions: This work may provide a novel insight into understanding the biomechanical effects behind the formation and damage of atherosclerotic plaques and propose a new strategy for preventing atherosclerotic diseases.

BACKGROUND Stenting appears to be a safe means of treatment for vertebral artery ostium stenosis with low complication rates and positive long-term effects, but the incidence of in-stent restenosis (ISR) after stenting is high. Different treatment strategies are applied for the revascularization of ISR; however, currently the optional approach is not recommended. The study was designed to investigate the feasibility, safety, and effectiveness of balloon-assisted angioplasty for the treatment of ISR after vertebral artery ostium stenosis. METHODS In this study, we included patients from the Department of Neurology, Lishui Hospital of Zhejiang University, who were treated with balloon-assisted angioplasty as a result of suffering from ISR after previously undergoing vertebral artery ostium stenting. We retrospectively analyzed the clinical and functional outcomes of the patients. RESULTS From January 2015 to December 2019, 11 patients were included in the study. The technical success rate reached 100% and the average operation time was 73 minutes. The Thrombolysis in Cerebral Infarction Score 2b-3 was acquired in all patients except 1 patient, who was presented with symptoms of hypoperfusion syndrome. The remaining 10 patients did not experience any intraoperative or postoperative complications. No restenosis, new cerebral infarction or transient ischemic attack were reported within 6 months of follow-up. CONCLUSION Balloon-assisted angioplasty could be feasible for the treatment of ISR after vertebral artery ostium stenting, however, more research is needed to confirm this.

Mycoplasma gallisepticum (MG) is the pathogen that causes chronic respiratory diseases in chickens. Gut microbiota plays an important role in maintaining body health and resisting respiratory infection, but the correlation between gut microbiota and MG infection is poorly defined. Therefore, in this study, the correlation between gut microbiota and MG infection was explored by disturbing gut microbiota in chickens with antibiotic cocktail. The results showed that the gut microbiota dysbiosis impairs pulmonary immune response against MG infection. It has been noted that MG colonization in the lung was significantly increased following gut microbiota dysbiosis, and this could be reversed by intranasally administrated toll-like receptor 2 (TLR2) ligand, recombinant chicken IL-17 protein or recombinant chicken granulocyte-macrophage colony-stimulating factor (GM-CSF) protein. In addition, the levels of short-chain fatty acids (SCFAs) and vitamin A were significantly reduced in gut microbiota dysbiosis group, however, butyric acid or vitamin A as feed additives promoted MG clearance in the lung of gut microbiota dysbiosis group via increasing TLR2/IL17/GM-CSF and host defense peptides genes expression. The present study revealed an important role of gut microbiota in the defense against MG colonization in the lung of chicken.

Introduction: Major depressive disorder (MDD) and Alzheimer’s disease (AD) are often co-existing in the elderly and have been suggested to share common pathological and physiological links. Understanding the connections between these two diseases could benefit for revealing new possible strategies of early diagnosis and therapeutic intervention. Methods: we conducted a meta-analysis to identify differentially expressed genes (DEGs) in MDD microarray datasets including 180 MDD and 281 control prefrontal cortex of brain samples. Using identified DEGs, we performed gene ontology (GO), pathway and protein-protein interaction (PPI) analysis. Results: We identified 1400 DEGs, of which 846 were upregulated and 554 was downregulated in MDD. 198 DEGs were found over-lapping between AD and MDD compared with the previous study on AD. The over-lapping DEGs were particularly enriched in the protein binding of gene ontology and Signal Transduction, Immune System, Metabolism of proteins as for pathways. CDC42 was the most important gene in PPI network which had the most connections with other genes.Conclusion: Our study shows that MDD and AD share significant common DEGs and pathways and add some new potential perspectives to the comprehensive neurobiologic model between MDD and the development of AD.

Eggplant is a vegetable crop with high economic value that is cultivated worldwide. The dwarf mutant is an important germplasm material that has been extensively used in crop breeding. However, no eggplant dwarf mutants have been reported, and little is known regarding the genes responsible for dwarfism in eggplant. In this study, we isolated an eggplant dwarf mutant (dwf) from an ethyl methyl sulfonate (EMS)-induced mutant library. Genetic analysis revealed that dwf was caused by a single recessive gene. A candidate gene SmCPR1, encoding cytochrome P450 reductases (CPR1), was identified by bulked segregant analysis (BSA). Mutation from G to A at 8216 bp of SmCPR1 resulted in mutation of the amino acid from valine to isoleucine. The results of KASP and Sanger sequencing further support the conclusion that SmCPR1 is a candidate gene responsible for the dwarfism of dwf. Moreover, the activity of SmCPR1 was significantly increased in dwf, which might be a response to dwarfism in dwf.

Background: Previous studies explored the associations between body weight index (BMI) at diagnosis, weight change after diagnosis and survival in amyotrophic lateral sclerosis (ALS). But significance of weight stability before diagnosis remains to be established.Objective: The aim of this study is to clarify the weight loss from baseline (6 months before diagnosis) to diagnostic and the effect on disease prognosis.Methods: Total of 911 patients were enrolled from 2014 to 2018 in West China Hospital of Sichuan University. BMI is divided into four subgroups: lean, normal, overweight, and obese. The formula for calculating the rate of weight change = (weight at baseline - weight at diagnosis)/weight at baseline * 100%. Survival analysis was performed using Kaplan-Meier curves and Cox proportional hazard models.Results: The mean age of onset was 55.4 ± 11.1 years. The percentage of overweight and obesity in ALS at baseline were significantly lower than healthy controls. The median of weight loss was 2.9%. 36.9% patients had weight loss more than 5%, and 16.5% of them lose weight more than 10%. Patients with bulbar onset, bulbar impairment, lower ALS functional rating scale-revised score had more serious weight loss. The Kaplan-Meier curve showed that, compared to other patients, patients with weight loss more than 10% had a shorter survival time (30.5 months vs. 48.8 months, log-rank p

Continual discoveries of new genes and unraveling the genetic etiology in amyotrophic lateral sclerosis (ALS) have provided greater insight into the underlying pathogenesis in motor neuron degeneration, as well as facilitating the disease modeling and the testing of targeted therapeutics. While, the genetic etiology accounted for two-thirds of FALS and approximately 11% of SALS in Caucasians. However, the contributions of these causative genes to ALS vary among different populations. Furthermore, the prominent difference between Chinese population and other ethnics remains a source of ongoing debate. We systemically reviewed genetics literature of Chinese ALS populations and updated the mutation frequencies of the main ALS-implicated genes aiming to determine the genetic features of ALS in Chinese population. We also reviewed the associations between ALS-implicated single nucleotide polymorphisms (SNPs) and the risk of ALS in Chinese population. A total of 116 studies were included in this analysis (86 gene mutation study articles and 30 SNPs study articles). The results showed that the overall gene mutation rates of ALS-related causative genes were 55.0% in familial ALS (FALS) and 11.7% in sporadic ALS (SALS) in Chinese population. In Chinese FALS, the highest mutation frequency was found in SOD1 gene (25.6%), followed by FUS (5.8%), TARDBP (5.8%), DCTN1 (3.6%) and C9orf72 (3.5%). In Chinese SALS, the highest mutation frequency was also identified in SOD1 gene (1.6%), followed by ANXA11 (1.4%), FUS (1.3%), SQSTM1 (1.0%), OPTN (0.9%) and CCNF (0.8%). The associations between several SNPs and risk of ALS were also reported in Chinese population. The genetic features of ALS in Chinese population are significantly different from those in Caucasian population, indicating an association between genetic susceptibility and origin of population. Further explorations are required to understand the gene complexity of ALS, including the contribution of most minor genes and the molecular mechanisms in ALS pathologies.

Dwarfism is a desirable trait in eggplant breeding, as it confers higher lodging resistance and allows simplified management and harvest. However, a few dwarf mutants have been reported, and the molecular mechanism underlying dwarfism in eggplant is completely unknown. Here, we report a dwarf mutant (dwf) isolated from an ethyl methyl sulfonate (EMS)-induced mutant library. The hypocotyl length, plant height, and length of internode cells of dwf were significantly decreased compared to those of the wild-type parent ‘14-345’ (WT). Differential gene expression analysis revealed that GA-related genes, including GA2ox and DELLA, were up-regulated whereas the gibberellin (GA3) content decreased in dwf. Moreover, exogenous GA3 treatment significantly increased the relative growth rate of dwf compared to WT, further indicating the important roles of GA in regulating the dwarf phenotype of dwf. Collectively, our findings shed light on GA-mediated dwarfism in dwf plants and offer a good germplasm that could be used for eggplant dwarfism breeding in the future.

BackgroundAccumulating evidence has revealed that peripheral immunity is involved in Parkinson’s disease (PD). However, the results regarding the percentage of T-cell subsets are inconsistent, and the changes of immunoglobins levels have been seldom studied in PD patients.MethodsSerum levels of the percentage of T-cell subsets and immunoglobulins were measured in 761 PD patients and 761 age- and gender-matched healthy controls. The correlations between the variables of peripheral immune activation (PIA) and the clinical characteristics of PD were analyzed using correlation analysis.ResultsThe pooled results showed that PD patients had higher proportional levels of CD3+ T and CD4+ T lymphocytes than healthy controls. CD8+ T cell percentages were similar in PD patients and controls, and the CD4/CD8 ratio was significantly higher in the PD population. No significant differences in IgG, IgA, or IgM levels between these two groups were found. CD4+ T cell percentage was inversely correlated with the H&Y stage, and IgG level was positively correlated with disease duration and UPDRS part III. Subgroup analyses showed that these associations existed in female patients, but not in male patients.ConclusionThe enhanced immune activation in the peripheral system is indicated in PD, and dynamic alterations in CD4+ T cell percentage and IgG level suggest an active role for peripheral immunity in the disease progression, especially in female PD patients.

Background Age at onset (AAO) is an essential feature of Parkinson's disease (PD) and can help predict disease progression and mortality. Identification of genetic variants influencing AAO of PD could lead to a better understanding of the disease's biological mechanism and provide clinical guidance. However, genetic determinants for AAO of PD remain mostly unknown, especially in the Asian population. Objectives To identify genetic determinants for AAO of PD in the Asian population. Methods We performed a genome-wide association meta-analysis on AAO of PD in 5166 Chinese patients with PD (Ndiscovery = 3628, Nreplication = 1538). We then conducted a further cross-ethnic meta-analysis using our results and summary statistics for the AAO of PD from the European population. Results The total heritability of AAO of PD was around 0.10 ~ 0.14, similar to that (~0.11) estimated in populations of European ancestry. One novel significant intergenic locus rs9783733 (NDN; PWRN4) was identified (P = 3.14E-09, beta = 2.30, SE = 0.39). Remarkably, this variant could delay AAO of PD by ~2.43 years, with a more considerable effect on males (~3.18 years) than females (~1.45 years). The variant was suggestively significant in the cross-ethnic meta-analysis and suggested a positive selection in the East Asian population. Additionally, cross-ethnic meta-analysis identified a significant locus rs356203 in SNCA (P = 2.35E-11, beta = -0.71, SE = 0.01). Conclusions These findings improve the current understanding of the genetic etiology of AAO of PD in different ethnic groups, and provide a new target for further research on PD pathogenesis and potential therapeutic options. © 2021 International Parkinson and Movement Disorder Society.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are genetically, pathologically and clinically-related progressive neurodegenerative diseases. Thus far, several SQSTM1 variations have been identified in patients with ALS and FTD. However, it remains unclear how SQSTM1 variations lead to neurodegeneration. To address this issue, we investigated the effects of ectopic expression of SQSTM1 variants, which were originally identified in Japanese and Chinese sporadic ALS patients, on the cellular viability, their intracellular distributions and the autophagic activity in cultured cells. Expression of SQSTM1 variants in PC12 cells exerted no observable effects on viabilities under both normal and oxidative-stressed conditions. Further, although expression of SQSTM1 variants in PC12 cells and Sqstm1-deficient mouse embryonic fibroblasts resulted in the formation of numerous granular SQSTM1-positive structures, called SQSTM1-bodies, their intracellular distributions were indistinguishable from those of wild-type SQSTM1. Nonetheless, quantitative colocalization analysis of SQSTM1-bodies with MAP1LC3 demonstrated that among ALS-linked SQSTM1 variants, L341V variant showed the significantly lower level of colocalization. However, there were no consistent effects on the autophagic activities among the variants examined. These results suggest that although some ALS-linked SQSTM1 variations have a discernible effect on the intracellular distribution of SQSTM1-bodies, the impacts of other variations on the cellular homeostasis are rather limited at least under transiently-expressed conditions.

Background: Fibrosis is an important histological change occurring in preeclamptic placentas, and might depends on the excess deposition of collagen I. However, the role of fibrotic placentas and collagen I in the pathogenesis of preeclampsia remains unclear. Methods: Collagen deposition and the expression of Collagen I in human placentas were analysed by Masson staining, Sirius red staining and western blotting. The role of collagen I in preeclampsia pathogenesis was studied in C57BL/6 mice.HTR-8/SVneo cells were used to investigate the mechanisms underlying the effects of collagen I in trophoblasts by transcriptome sequencing and pharmacological agonists. Finding: Human preeclamptic placentas exhibited a higher degree of fibrosis in stem villi and terminal villi than normal placentas, and were characterized by collagen I deposition. In vivo, a single injection of collagen I on gestational day 0.5 led to an increase in systolic pressure of pregnant mice from gestational day 4.5 -17.5, to a decrease in weight and number of viable embryos, and to enhanced placental collagen I expression, and degree of fibrosis compared with control mice. In vitro, collagen I attenuated the proliferation and invasion of HTR-8SV/neo cells. This effect could be reversed by treatment with agonist s of ERK and β-catenin. Transcriptome sequencing demonstrated that pathways related to cell proliferation and invasion were significantly downregulated in HTR-8/SVneo cells. Interpretation: Collagen I induced preeclampsia-like symptoms by suppressing the proliferation and invasion of trophoblasts through inhibition of the ERK phosphorylation and WNT/β-catenin signalling pathways. Funding: National Natural Science Foundation of China and Guangdong Province. Declaration of Interest: The authors declare no conflicts of interest. Ethical Approval: The collection of placentas was approved by the Ethics Committee of Nanfang Hospital（NFEC-2017-055）. All participants gave written consent prior to donating their placenta.

It is of great clinical significance to study the relationship between coronary bifurcation's morphometrical feature change and coronary artery disease (CAD) lesion. The purpose of this study is to determine the morphological changes in patients with CAD lesion when compared with non-CAD subjects and to find indicators that may be used for cardiovascular disease diagnosis. Computed tomography angiography images from Southern Chinese populations were used to reconstruct three-dimensional coronary arterial trees. Murray's law was introduced to assess the level of deviation of the realistic vascular networks from their optimal state. The results showed CAD Left had the highest deviation values of

Objectives: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and sporadic Creutzfeldt–Jakob disease (sCJD) share similar clinical features. Here, we present two unusual cases of anti-NMDAR encephalitis who were misdiagnosed as sCJD at first.Methods: We described two patients' clinical manifestations, as well as the string of symptomatological evolution, treatments, and follow-up results.Results: Our patients presented with rapidly progressive dementia, memory problems, psychiatric symptoms, and movement disorders, and we considered all these symptoms as a presenting feature of sCJD at first, but the cerebrospinal fluid examination showed positive results for both the 14-3-3 protein and antibodies against NMDAR. Immunomodulatory treatment led to a resolution of these deficits, and both of them remained in remission after treatment.Conclusion: Anti-NMDAR encephalitis can present with rapidly progressive cognitive decline, and sometimes laboratory investigations can be misleading. The examination for the presence of NMDAR antibodies is necessary, even with the presence of 14-3-3 protein. Early immunomodulatory therapy should be considered, especially for patients with high titers of NMDAR antibodies.

Background: Studies have investigated the lipid profile in amyotrophic lateral sclerosis (ALS), including the levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), and higher low-density lipoprotein (LDL), and the associations with mortality of ALS, but the results were inconsistent. Therefore, we conducted this meta-analysis to systematically answer this unsolved question. Methods: We searched all the related studies that probed into the association between serum lipid levels and ALS based on PubMed, EMBASE, and Cochrane library from January 1990 to July 2020. The quality of the included studies was evaluated by using the Newcastle–Ottawa Scale (NOS). All the statistical analyses of this meta-analysis were performed using the Stata version 12.0 software. Results: Fourteen studies with a total of 3,291 ALS patients and 3,367 controls were included. Among them, 10 studies compared the lipid profile between ALS patients and controls. The results indicated that compared with controls, ALS patients from both Europe and Asia had lower levels of TG and HDL, but the levels of TC and LDL were higher in ALS patients from Europe. However, after systemic analyses, the altered TC level was significant only in Asian ALS patients; the differences of other lipids were not significant. Concerning the effect of lipid profile on mortality of ALS, analyses of four cohort studies showed that the levels of all lipids were not associated with overall mortality in ALS. Conclusion: The results of the present study showed that Asian ALS patients had lower TC levels than controls, and the levels of all lipids were not associated with mortality of ALS.

α-synuclein is involved in the pathogenesis of multiple system atrophy (MSA) and can be regulated by peripheral immune activation (PIA). We aimed to clarify the correlations between PIA and the prevalence of MSA and to analyze the role of PIA in the progression of the disease. A total of 321 patients with probable MSA and 321 age- and gender-matched healthy controls were included in this study. Lymphocyte subsets, including CD3+, CD4+, and CD8+ cells, and the levels of immunoglobulins IgG, IgM, and IgA were evaluated. The proportions of CD3+ and CD4+ T-lymphocytes were significantly increased in MSA patients compared with those of normal controls. In addition, the ratio of CD4+ to CD8+ cells was significantly increased in male MSA patients and IgG concentrations were decreased in female MSA patients. Furthermore, the concentrations of IgM in female MSA patients were dynamically different at various disease stages and gradually decreased from the early stage until the end stage of the disease (p = 0.029). Other detected immunological indexes were not significantly different during the entire disease course. In this study, high proportions of CD3+ and CD4+ T-lymphocytes and decreased IgG levels were associated with an increased risk for MSA in a Chinese patient population. In addition, PIA may be involved in the progression of MSA.

Serum creatinine (Cr) is a biosynthetic product of creatine phosphate metabolism in muscles and is closely related to total muscle mass, but it is not easily affected by diet. Several studies have tried to explore the role of serum Cr levels in amyotrophic lateral sclerosis (ALS), but the results were inconsistent. Therefore, our study aims to explore the differences of serum Cr levels between ALS patients and controls and whether serum Cr at baseline is an independent predictor of survival. Methods: We searched all the related studies that probed into the association between Serum Cr levels and ALS based on PubMed, EMBASE and Cochrane library from October 1952 to February 2019. The quality of the included studies was evaluated by using Newcastle-Ottawa Scale (NOS), and all the statistical analysis of this meta-analysis was performed by Stata version 12.0. Results: Eight studies with a total of 11377 ALS patients and 937 controls were included. Among them, five studies indicated that ALS patients had lower serum Cr levels (SMD = −0.78, 95%CI [−0.97, −0.60]) compared to controls, and three studies showed that higher serum Cr levels in ALS patients were related to lower overall mortality (HR 0.89, 95%CI [0.80, 0.99]). Conclusion: The levels of serum Cr in ALS patients are significantly lower than those in controls, and they are inversely related to overall mortality in ALS patients. Therefore, the serum Cr, an easily accessible serological factor, may serve as a prognostic biomarker.

The glycosyltransferase 8 domain containing 1 (GLT8D1) gene was identified to be an amyotrophic lateral sclerosis (ALS)-causative gene via pedigree cosegregation and burden analysis. In the present study, 977 Chinese sporadic ALS (sALS) cases and 47 Chinese familial ALS (fALS) cases underwent whole-exome sequencing. Rare variants with minor allele frequency0.1% in GLT8D1 were analyzed. One likely pathogenic variant in the exon 4 was identified in a fALS case and validated within the family. Moreover, 3 rare variants of uncertain significance in 4 patients with sALS and 1 rare variant of uncertain significance in 1 patient with fALS were also identified. Furthermore, by using the East Asian controls from the gnomAD database, there was no significant enrichment of rare variants of GLT8D1 at the whole-gene level or the exon 4-specific level in Chinese patients with sALS. In conclusion, cosegregation findings further support the pathogenic role of GLT8D1 in fALS. However, no pathogenic mutation and no enrichment of rare variants were found in patients with sALS, which implies that GLT8D1 may not play a role in Chinese patients with sALS.

With the increasing incidence of papillary thyroid cancer (PTC), it is important to risk-stratify patients who may have a more aggressive tumor biology. The present study aimed to evaluate the risk factors for lymph node metastasis (LNM) in patients with PTC, which may provide a significant reference for clinical diagnosis and treatment. In total, 1,045 patients with PTC [313 with PT microcarcinoma (PTMC) and 732 with non-PTMC] between August 2016 and August 2019 were investigated. The B-type Raf kinase (BRAF) V600E mutation was tested in all samples. The clinical data (sex, age, tumor location, sample type and pathological features) were retrospectively analyzed. Logistic regression analysis was performed to evaluate independent risk factors for LNM. A total of 181/313 (57.8%) PTMC cases and 145/732 (19.8%) non-PTMC cases had a BRAF V600E mutation. In the PTMC cases, significant differences in sex and sample type were identified (BRAF V600E mutation vs. wild-type). In the non-PTMC cases, significant differences in sex and age were identified (BRAF V600E mutation vs. wild-type). Female sex and tumor diameter ≤1 cm were significant independent predictors of LNM in PTC. In PTMC, female sex was a significant independent predictor of LNM. A bilateral tumor was an independent protective factor for LNM in PTC, PTMC and non-PTMC. The BRAF V600E mutation rate of ultrasound-guided fine-needle aspiration cytology was higher compared with FFPE in PTMC (P=0.018). In contrast to previous studies, the results of the present study suggested that being female and having a tumor of diameter ≤1 cm were risk factors for LNM, and that the BRAF wild-type of PTMC may be more aggressive than other types. Notably, the position of the tumor in the bilateral thyroid was also an independent protective factor for LNM. Therefore, ultrasound-guided fine-needle aspiration should be recommended for gene analysis (BRAF V600E) in PTMC. In addition, clinicians should consider an individualized treatment according to gene mutations, sex, age, tumor size and the location of the tumor, in order to achieve an improved therapeutic efficacy.

Background: In recent years, the role of iron metabolism in amyotrophic lateral sclerosis (ALS) attracts more and more attention, and some studies have focused on the link between abnormal serum iron indicators and ALS. However, there are still big conflicts and inconsistency among different studies. To study the possible relationship between ALS and disturbed iron metabolism, we conducted this meta-analysis to conclude characteristics of abnormal serum iron-status indicator changes in ALS patients.Methods: We searched and screened main databases, including the PubMed, Embase, and Cochrane Library, to find studies related to the association between iron metabolism and ALS. The Revman 5.3 software was used to conduct meta-analysis.Results: Eleven studies were finally included in our analysis, composed of 1,599 ALS patients and 1,255 controls in total. The results showed that the ferritin level was much higher in ALS patients compared with controls (MD = 70.48, 95% CI [51.41, 89.55], p < 0.00001), and the transferrin level was decreased in ALS patients compared with controls (SMD = −0.28, 95% CI [−0.38, −0.18], p < 0.00001), while there was no statistical difference in iron levels (SMD = 0.48, 95% CI [−0.07, 1.03], p = 0.09) between ALS patients and controls.Conclusions: Our research finds unusual changes in several indicators representing iron status, which suggest possible iron metabolism abnormalities in ALS patients. That may provide evidence for the link between iron metabolism and the pathogenesis of ALS.

Better understanding of survival factors in amyotrophic lateral sclerosis (ALS) could help physicians and patients schedule therapeutic interventions. We conducted a study to evaluate the predictive factors associated with longer survival and construct prognostic nomogram in ALS patients. A total of 553 ALS patients were enrolled and divided into 2 groups: a training set and a validation set. Risk factors for survival were identified using logistic regression analysis, and a nomogram created by R program was performed to predict the probability of longer survival in the training set; then receiver operating characteristic (ROC) analysis was applied to assess predictive value of the nomogram model. The median survival time was 3.2 years for all patients. Multivariate analyses revealed that age of onset, rate of disease progression, hemoglobin A1c (HbA1c) level, body mass index, creatinine, creatine kinase (CK), and non-invasive positive pressure ventilation (NIPPV) were independent predictors of longer survival. A nomogram based on the above seven predictive factors was developed to predict the possibility of longer survival. The ROC curve of the nomogram demonstrated good discrimination ability with an AUC of 0.92 (95% CI: 0.88-0.96) in the validation set. In ALS, serum CK, creatinine and HbA1c levels at baseline were independent biomarkers of longer survival. The prognostic nomogram model that integrated all significant independent factors for those who survived longer than 3 years provides an effective way to predict the probability of longer survival and can help doctors evaluate the disease progression and give personalized treatment recommendations.

Bingbing Liu,1 Xueping Chen,1 Yang Li,1 Hui Liu,2 Shasha Guo,2 Ping Yu3 1Nursing Department, Qianjiang College, Hangzhou Normal University, Hangzhou, China; 2Medicine Department, Hangzhou Normal University, Hangzhou, China; 3School of Computing and Information Technology, Faculty of Engineering and Information Sciences, University of Wollongong, Wollongong, NSW, Australia Background: Dementia adds burden to society. As it is not curable, physical exercise activities are optimal to improve the physical strength and quality-of-life of people with dementia. Aim: Design, implementation, and examination of a set of passive finger exercises and their effects on improving grip strength and activities of daily living (ADL) for older people with dementia. Methods: Forty older people with dementia were recruited and randomly allocated into an experimental group and a control group, each with 20 people. The control group received routine nursing care. In addition to this, the experimental group received 25-minutes of passive finger exercises every day for 12 weeks. The health outcomes measured were grip strength and ADL, before and after the intervention. Grip strength was assessed by electrical hand muscle dynamometer. ADL were assessed with Barthel index. Results: Although there was no effect on grip strength, passive finger exercises led to significant improvements in urinary control, defecation function, and overall ADL in comparison with the control group. Implications for practice: Passive finger exercises can be integrated into physical exercise programs for older people with dementia to improve their urinary control, defecation function, and ADL. Keywords: physical exercise, passive finger exercise, grip strength, urinary control, defecation, activities of daily living, ADL, dementia

Objective Autoimmune encephalitis associated with antibodies against gamma-aminobutyric-acid B receptor (GABABR) has not been described in detail in Chinese patients. Methods Patients with anti-GABABR encephalitis treated between January 2013 and December 2015 were analyzed in terms of clinical characteristics, laboratory findings, tumor presence, autoantibody patterns, treatment response and outcomes. Results Eleven patients were identified (male, N = 8; female, N = 3), with the median age of 51 years. All patients presented with seizures (N = 11; 100%), and they were given anti-epileptic drugs and first-line immunotherapy to address the disease. Seizures always accompanied by limbic manifestations (N = 10; 90.9%). Extralimbic manifestations were present in 4 patients (N = 4; 36.4%). MRI Brain abnormality with increased medio-temporal lobe T2/FLAIR signal were present in 2 patients (N = 2; 18.2%), and epileptiform epileptiform activity on electroencephalography were observed in 2 patients (N = 2; 18.2%). Small-cell lung cancer was histologically confirmed in 3 patients (N = 3; 27.3%). Seven patients showed good outcomes (mRS 1-2; N = 7; 63.6%), one patient showed poor neurological status with minimal changes (mRS 4; N = 1; 9.1%), and three patients died during follow-up (mRS = 6; N = 3; 27.3%). Outcomes were correlated with age-of-onset, and were worse among older patients (P = 0.0112). Conclusion Anti-GABABR encephalitis is a potentially treatable disorder involving seizures as the most predominant presentation at admission. It should be considered as a possible diagnosis in middle-aged and older patients with refractory new-onset epilepsy.

The vesicular monoamine transporter type 2 (VMAT2) and transmembrane Protein 106B (TMEM106B) were reported to be associated with neurodegenerative diseases. Recent studies found that two polymorphisms (rs363371 and rs363324) in VMAT2 might be a risk factor for Parkinson's disease (PD) in Caucasians, while the two other variants (rs1990622 and rs3173615) in TMEM106B increased the risk for frontotemporal dementia (FTD). Considering the overlap between clinical manifestation and pathologic characteristics in neurodegenerative diseases, we conducted a large-sample study to investigate the associations between these four polymorphisms and the risk for PD, sporadic amyotrophic lateral sclerosis (SALS), and multiple system atrophy (MSA) in a Chinese patient population.A total of 1121 PD, 863 SALS, and 356 MSA patients, as well as 829 healthy controls (HCs), were included in the study. These four polymorphisms were genotyped using Sequenom iPLEX Assay technology.Significant differences were found in the genotype distribution of VMAT2 rs363371 between SALS patients and HCs (p=0.001). In an additive model, "GG" of rs363371 significantly decreased the risk for SALS (p0.001, OR: 0.49, 95% CI [0.36-0.67]). The frequencies of minor alleles for rs1990622 and rs3173615 in TMEM106B were significantly different between PD patients with initial symptoms of tremor and rigidity/bradykinesia (p=0.001), and between patients with initial symptom of rigidity/bradykinesia and HCs (p0.001). The minor alleles "T" of rs1990622 and "C" of rs3173615 increased the risk for PD patients with initial symptom of rigidity/bradykinesia (OR: 1.21[1.10-1.34] and OR: 1.19[1.07-1.31], respectively). No differences were found in the genotype distribution and allele frequency of the four polymorphisms between MSA patients and HCs.In this Chinese patient population, "GG" of rs363371 in VMAT2 may reduce the risk for SALS, while minor alleles of rs1990622 and rs3173615 in TMEM106B may be associated with PD patients with initial symptom of rigidity/bradykinesia.

Phthalates are commonly used in plastic products in daily life. The endocrine-disrupting effects of phthalates have been widely reported. Accumulating evidence from human cohorts and lab animals indicate exposure to phthalates might impair neurodevelopment. However, the direct causal relationship and mechanism between phthalates with neurodevelopment and neurotoxicity have not been firmly established. We found that phthalates (i.e. DBP, DINP, BBP) disrupted the expression of estrogen receptors (esr1, esr2a, esr2b), and impaired neurogenesis in the brain of zebrafish during embryonic development. Moreover, the abnormal expression of estrogen receptors, especially esr2a, was partly rescued in zebrafish which exposed to phthalates, with the estrogen receptor antagonist tamoxifen. Hence, impaired neurogenesis of zebrafish exposed to phthalates was partly reversed by tamoxifen treatment. Moreover, our results show that induced pluripotent stem cells (iPSC)-derived human neurons exposed to phthalates triggered double-strand DNA breaks in vitro. Overall, this study demonstrates that exposure to phthalates affects neurodevelopment in zebrafish embryos and induces neurotoxicity in human neurons partly through disrupting the expression of estrogen receptors.

Introduction/Background The purpose of our study was to presentgenetic susceptibility and treatment related gene profiling in Chinese ovarian cancer patients. Methodology We have applied next-generation sequencing in consecutive patients who underwent primary surgery for ovarian cancer since 2016 at our institution. 241 patients have been enrolled for blood tests so far. Paired tumor samples from 62 patients have been tested for somatic deleterious mutations. Results The median (range) age of patients was 54 (35–83) years old. 27.4% (66/241) patients had germline deleterious mutations. The most frequently reported genes were as follows: 29 (12.8%) BRCA1 mutations, 19 (7.9%) BRCA2 mutations, 6 (2.5%) RAD51C mutations, and 6 (2.5%) RAD51D mutations. Other mutated genes investigated included BRIP1 (2), CHEK2 (2), RAD50 (2), MRE11A (2), PMS1 (1) and MLH1 (1). 4 patients had dual gene mutation, that is BRCA1/PMS1, BRCA1/RAD50, BRCA2/BRIP1, and BRCA2/RAD51D. For the paired tumor samples, 19 (30.6%) deleterious TP53 mutations were identified, 4 patients had somatic BRCA1 mutations and 1 patient had somatic BRCA2 mutation. Conclusion Our results suggest a comprehensive profiling for Chinese ovarian cancer patients. Somatic genetic test could help better stratify patients for individualized treatment. Disclosure Nothing to disclose.

Metabolic dysfunction is a hallmark of age-related neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). But the crosstalk between metabolic alteration and disease progression in ALS is still largely unknown. Glycogen, a branched polymer of glucose residues, is universally recognized as the energy reserve of the central nervous system (CNS), where its aberrant accumulation instigates neurodegeneration. Glycogen was reported to be accumulated in both CNS and visceral organs of SOD1G93A mice, a well-known ALS model, and contributes to the pathological process of ALS. However, the accumulative patterns and mechanisms are not well elucidated. Here, we provide extensive evidence to demonstrate that glycogen accumulated in the lumbar spinal cord of ALS mice along with the disease progression, but not in the motor cortex. This regional accumulation of glycogen was caused by deteriorated glycogenolysis, which was triggered by decreased glycogen phosphorylase, brain form (PYGB). Moreover, miR-338-3p, an elevated miRNA in the spinal cord of SOD1G93A mice, directly targeted PYGB and was responsible for the decreased glycogenolysis and subsequent glycogen accumulation. Our work is helpful for better understanding of of of metabolic dysfunctions in ALS and provides novel targets for the therapeutic intervention in the future.

OBJECTIVE To update the oncological results and identify recurrent risk factors in young patients with early stage cervical cancers following abdominal radical trachelectomy (ART). DESIGN Retrospective study. SETTING A university-based cancer hospital. POPULATION Three hundred and thirty-three patients. METHODS We conducted a retrospective analysis from a prospectively maintained database of patients undergoing ART from April 2004 to December 2017. MAIN OUTCOME MEASURES Survival rate, clinicopathological factors related to recurrences. RESULTS Two hundred and seventy-one patients had squamous carcinomas (SCC), 51 had pure adenocarcinomas (AC), and 11 had adenosquamous carcinomas (AS). One hundred thirty-two women (39.6%) had tumours ≥2 cm. With a median follow up of 56 months (range, 6-169), 11 patients (3.3%) had recurrence, and five patients (1.5%) died. The cumulative 5-year recurrence-free survival and overall survival rates were 96.3 and 98.6%, respectively. The recurrence rate in women with tumours ≥2 cm was comparable to that in patients with tumours

Objective: Little is known whether disease clinical stage would influence the serological values in Amyotrophic lateral sclerosis (ALS). We aimed to explore the association between the levels of serological factors with clinical progression determined by the King’s College staging system. Methods: ALS Patients were registered from May 2008 to December 2016. The differences of serological values between patients and healthy controls, and the correlation of these serological values with disease stage were examined. Results: A total of 571 patients and 571 age-/gender-/BMI-matched healthy controls were included. The levels of creatinine, uric acid (UA), albumin, total protein, total cholesterol, and high-density lipoprotein (HDL) were significantly lower, and the low-density lipoprotein/HDL ratio was higher in ALS patients than those in healthy controls. The levels of UA, albumin, and total protein were significantly reversely correlated with diseases stages. The longitudinal observation of 81 ALS patients also showed that the levels of UA, creatinine, albumin, total protein, and HDL were significantly decreased in the second hematological examinations. Conclusions: In the present study, ALS patients and control subjects were evenly matched with regard to sex, age, and BMI value, this finding could be considered as a metabolite signature in ALS. The changes of metabolite-based serological factors with progression of disease stage might be related to the pathophysiology of disease, and might have clinical utility in clinical practice.

Recently, LRP10 has been identified as a causative gene for Parkinson's disease (PD). However, subsequent studies showed inconsistent conclusions. To explore its relevance to PD, we systematically analyzed LRP10 rare mutations in a large Han Chinese familial PD cohort of 385 unrelated probands using segregation analysis, transcriptional effect analysis, and burden test. As a result, 3 missense variants and 1 splicing region variant in LRP10 were identified in 4 probands. Segregation analysis revealed 1 variant p.Arg66His cosegregating with PD status, 1 variant p.Ala613Ser not, and the other variant p.Gln581His unknown. The variant c.406+5G>T located at the splicing region has no effect on splicing, suggesting it is likely a rare neutral intronic variant. The burden test suggested no significant over-representation of rare variants in PD probands. Therefore, more robust independent studies are warranted to explore the pathogenicity of LRP10 mutations.

The hexanucleotide repeat expansions in the C9ORF72 gene has been found in some patients with atypical Parkinsonism. A number of hexanucleotide repeats were examined in a Chinese population, including 619 patients with Parkinson's disease (PD), 381 patients with multiple system atrophy (MSA), and 632 healthy controls. We did not identify any pathogenic repeat expansions in either patients or controls, and any associations between repeats number and disease risk. C9ORF72 expansions are not involved the wider spectrum of Parkinsonism.

Neurotoxicity is one of the major potential side effects of colistin therapy. However, the mechanistic aspects of colistin-induced neurotoxicity remain largely unknown. The objective of this study was to examine the effects of colistin on the blood-brain barrier (BBB) and amino acid neurotransmitters in the cerebral cortex of mouse. Mice were divided into four groups (n=5) and were administrated intravenously with 15mg/kg/day of colistin sulfate for 1, 3 and 7days successively while the control group was administrated intravenously with saline solution. The permeability and ultrastructure of the BBB were detected using the Evans blue (EB) dye and transmission electron microscopy (TEM), and the expression of Claudin-5 were determined by real-time PCR examination and western blotting. The brain uptake of colistin was measured by high-performance liquid chromatography (HPLC). The effects of colistin on amino acid neurotransmitters and their receptors were also examined by HPLC and real-time PCR. The results of EB extravasation, TEM and expression of Claudin-5 showed that colistin treatment did not affect the BBB integrity. In addition, multiple doses of colistin could induce accumulation of this compound in the brain parenchyma although there was poor brain uptake of colistin. Moreover, colistin exposure significantly increased the contents of glutamate (Glu) and gamma aminobutyric acid (GABA), and enhanced the mRNA expression levels of gamma aminobutyric acid type A receptor (GABAAR), gamma aminobutyric acid type B receptor (GABABR), N-methyl-d-aspartate 1 receptor (NR1), N-methyl-d-aspartate 2A receptor (NR2A) and N-methyl-d-aspartate 2B receptor (NR2B) in the cerebral cortex. Our data demonstrate that colistin is able to accumulate in the mouse brain and elevate the levels of amino acid neurotransmitters. These findings may be associated with colistin-induced neurotoxicity.

Mutations in the coiled-coil-helix-coiled-coil-helix domain-containing protein 10 gene (CHCHD10), involved in mitochondrial function, have recently been reported as a causative gene of amyotrophic lateral sclerosis (ALS). The aim of this study was to obtain the mutation prevalence of CHCHD10 and the phenotypes with mutations in Chinese ALS patients. A cohort of 499 ALS patients including 487 sporadic ALS (SALS) and 12 familial ALS (FALS), from the Department of Neurology, West China Hospital of Sichuan University, were screened for mutations of all exons of the CHCHD10 gene by Sanger sequencing. Novel candidate mutations or variants were confirmed by polymerase chain reaction-restriction fragment length polymorphism in 466 healthy individuals. All patients identified with mutations of CHCHD10 gene were screened for mutations of the common ALS causative genes including C9orf72, SOD1, TARDBP, FUS, PFN1, and SQSTM1. Three heterozygous variants, including two missense mutations (c.275A > G (p.Y92C) and c.306G > C (p.Q102H)) and a synonymous change c.306G > A (p.Q102Q), were found in exon 3 of CHCHD10 in three alive SALS individuals (with the longest disease duration of 8.6 years), all of which were not detected in healthy controls. No mutation in CHCHD10 was identified in FALS patients. No mutation was found in the aforementioned common ALS causative genes in the patients who carried CHCHD10 mutations. The mutation frequency of CHCHD10 (0.4 %, 2/487) in a Chinese SALS population suggests CHCHD10 gene mutation appears to be an uncommon cause of ALS in Chinese populations. CHCHD10 mutations are associated with a slow progression and long disease duration.

Background Non-motor symptoms (NMS) are gaining increasing relevance in the management of Parkinson's disease (PD), but little is known about their progression, especially among patients with different ages. Methods A total of 117 PD patients who were divided into four age groups ( 70years old) were included to assess NMS at baseline and follow-up visit (21.6±5.6months). The frequency and severity of NMS were assessed using the Non-Motor Symptom Scale (NMSS). Results After adjusting for confounding factors, patients at the last visit had significantly higher frequency of "Difficulty falling asleep" item ( p =0.034) and "Urinary" domain ( p =0.017), and higher total NMSS score ( p =0.011) as well as scores for "Sleep/fatigue" ( p =0.013) and "Sexual dysfunction" ( p =0.014) domains and scores for "Fatigue" ( p =0.004), "Lack of motivation" ( p =0.033), "Interest in sex" ( p =0.014) and "Problems having sex" ( p =0.031) items than patients at baseline. The frequency changes of each NMS among four age groups exhibited an anfractuous result, while the annual severity changes of each NMS were not significant different among four age groups. Multinomial logistic regression model indicated that age had no correlation with the changes of NMS frequency and severity. Conclusions The severity of NMS in PD tends to become progressively worse with the course of the disease. Age is not related to the progression of NMS in PD.

Background: Early accurate detection of coronary artery disease (CAD) is one of the most important medical research areas. Researchers are motivated to utilize machine learning techniques for quick and accurate detection of CAD. Methods: To obtain the high quality of features used for machine learning, we here extracted the coronary bifurcation features from the coronary computed tomography angiography (CCTA) images by using the morphometric method. The machine learning classifier algorithms, such as logistic regression (LR), decision tree (DT), linear discriminant analysis (LDA), k-nearest neighbors (k-NN), artificial neural network (ANN), and support vector machine (SVM) were applied for estimating the performance by using the measured features. Results: The results showed that in comparison with other machine learning methods, the polynomial-SVM with the use of the grid search optimization method had the best performance for the detection of CAD and had yielded the classification accuracy of 100.00%. Among six examined coronary bifurcation features, the exponent of vessel diameter (n) and the area expansion ratio (AER) were two key features in the detection of CAD. Conclusions: This study could aid the clinicians to detect CAD accurately, which may probably provide an alternative method for the non-invasive diagnosis in clinical.

IntroductionPancreatic cancer is a highly aggressive digestive system tumour with poor prognosis. Venous thromboembolism (VTE) is a well-known complication of pancreatic cancer, and tissue factor (TF) contributes to the generation of a hypercoagulable state and thrombotic disease in pancreatic cancer. Several studies showed that an elevated TF level was related to the development of VTE and influenced the survival of patients with pancreatic cancer. Thus, we wish to conduct a systematic review of literature to clarify the prognostic significance of TF in pancreatic cancer.Methods and analysisStudies comparing the circulating microparticle-associated TF (MP TF) level between patients who had pancreatic cancer with and without VTE will be included to evaluate the roles of TF in VTE development. Studies comparing the survival data between patients with high TF expression and low TF expression will also be included to explore the association of TF expression with patient survival. The outcomes are plasma MP TF level and survival endpoints (overall and progression-free survival), respectively. Primary studies of any type published in English will be included. Two reviewers will search Medline, EMBASE and Cochrane databases from inception to June 2020, retrieve relevant studies, and independently select the literatures and extract data from the included studies. The quality of each included study will be assessed by the Newcastle-Ottawa Scale score. The HR and 95% CI of each study will be pooled for survival outcome, and the standardised mean difference (SMD) with 95% CIs will be used for continuous outcomes. If meta-analysis is inappropriate, the result will only be reported qualitatively. Subgroup and sensitivity analyses will be considered to identify sources of heterogeneity. The Grades of Recommendation, Assessment, Development and Evaluation method will be applied to assess the level of evidence of this systematic review.Ethics and disseminationThere are no concerning ethical issues. The results will be published.PROSPERO registration numberCRD42019133665.

Objective: It is important to explore the utility of clinical staging systems in the management of amyotrophic lateral sclerosis (ALS). Our aim was to assess the validity of King's College in a Chinese ALS cohort, by evaluating the duration and informativeness of each stage and examining the association between stage and prognosis.Methods: From May 2008 to December 2016, patients with a likely diagnosis of ALS were registered. We prospectively assessed the progression of the patients through the stages and calculated the duration of each stage.Results: The median duration in Stage 1 was 12.00 months, Stage 2 7.50 months, Stage 3 6.50 months, and Stage 4 4.10 months. Subset analysis revealed that the spinal-onset and early-onset patients had a longer median time in Stage 1 compared to bulbar-onset and late-onset patients, respectively. Riluzole treatment extended the durations of Stages 1 and 2, and the effect was maintained in patients with long-term use of riluzole (>6 months). Patients who initiated long-term riluzole therapy early, in Stage 1 or 2, had a longer Stage 2. Patients who received percutaneous gastrostomy endoscopy (PEG) or non-invasive positive-pressure ventilation (NIPPV) showed longer durations of Stage 4. The differences in survival time measured from each stage to death or censor date were significant.Conclusions: We validated the King's College staging system in a Chinese population, and showed this system to be useful in clinical practice. Patients with bulbar-onset or an age of onset>45 years tended to have rapidly progressing ALS. Riluzole may be more effective when initiated in an early disease stage and continued long-term. PEG and NIPPV treatments can extend disease duration of Stage 4.

Objectives To explore the natural history, clinical features, and survival relevance of patients presenting with amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) with different phenotypes. Methods All patients were prospectively enrolled in a hospital-based register from 2006 to 2015. Cases were classified according to established phenotypes: classic, bulbar, flail arm, flail leg, upper motor neuron dominate, respiratory, pure lower motor neuron and pure upper motor neuron. Survival was analyzed using Kaplan-Meier curves and Cox regression analysis. Results A total of 1157 patients with complete clinical information were registered in the current cohort study. The classic phenotype was the most frequent phenotype. The mean age of onset, diagnostic delay, smoking status, exposure to pesticides and mean survival time were significantly different among different phenotypes. The median survival time was 3.1 years for all patients. At the end of the analysis, the 3-year survival rate was 62.1%, the 5-year survival rate was 39.6%, and the 10-year survival rate was 22.0%. The Cox analysis revealed that the disease phenotype was an independent predictor of survival (hazard ratio = 0.825, P Conclusions This study showed the natural history data of ALS/MND and supported the theory that varied disease phenotypes had different clinical, demographic and prognostic characteristics, which provided the basis for analysis of future management and treatment for ALS/MND. Furthermore, the phenotypic expression of ALS/MND with distinctive characteristics is important for providing complementary information for identifying the underlying mechanisms of the diseases.

To investigate the occurrence and clinical associations of festination in Chinese patients with Parkinson's disease (PD).A total of 480 PD patients were recruited in this cross-sectional study. Assessments scales included the Unified PD Rating Scale (UPDRS) part III, PD Questionnaire-39 (PDQ-39), Non-Motor Symptoms Scale (NMSS), Mini-Mental State Examination (MMSE), frontal assessment battery (FAB), Montreal Cognitive Assessment (MoCA), Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA).One hundred and forty PD patients (29.2%) reported festination. Festination occurred more frequently in patients with lower limbs as the site of onset and patients with longer disease duration or higher Hoehn and Yahr (HY) stage (P0.05). The mean age, levodopa and entacapone use, incidences of motor complications, falls and freezing of gait, and the scores for the UPDRS part III, NMSS, HAMD and HAMA were higher in patients with festination than those without festination (P0.05). There were no differences in the scores for the PDQ-39, MMSE, FAB and MoCA between the patients with and without festination. The binary logistic regression model indicated that UPDRS part III, lower limbs as the site of onset, freezing of gait and falls were associated with festination.Festination is a relatively common disabling symptom in Chinese PD patients. Patients with lower limbs as the site of onset and more severe disability were more likely to experience festination. Festination in PD is not related to non-motor symptoms and cognitive dysfunction.

Previous studies have found an association between the granulin gene rs5848 and microtubule-associated protein tau gene (MAPT) rs242557 polymorphisms and susceptibility to Parkinson's disease (PD). However, the results of association studies between the two polymorphisms and PD have been inconsistent. Given the overlap in clinical and pathological characteristics of PD and multiple system atrophy (MSA), we examined the associations of these two polymorphisms with PD and MSA in a subset of the Chinese population.In total, 1270 PD patients, 360 MSA patients and 830 healthy controls (HCs) were included in the study. All subjects were genotyped for the two polymorphisms using Sequenom iPLEX Assay technology. After combining our results with the available published data, a meta-analysis was conducted to investigate the association between MAPT rs242557 and the risk of PD.The minor allele "T" of GRN rs5848 decreased the risk for PD (p = 0.0309, odds radio [OR], 0.86; 95% CI, 0.76-0.99). No differences in the genotype distributions and minor allele frequency (MAF) of MAPT rs242557 were observed between the PD and the HCs in our Chinese population. Our meta-analysis revealed an association between MAPT rs242557 and PD in Caucasian and Asian population in a recessive model (p = 0.049 and p = 0.046, respectively). However, no significant differences in the genotype distributions and MAFs of the two polymorphisms were found between the MSA patients and HCs.Our results indicate that GRN rs5458 may decrease the risk of PD in Chinese individuals, and the MAPT rs242557 is marginally associated with PD.

Although rs75932628 in triggering receptor expressed on myeloid cells 2 (TREM2) was shown to increase the risk for Alzheimer’s disease, there is no agreement on the association between this variant and the risk for Parkinson’s disease (PD). Considering the overlapping of clinical manifestation and pathologic characteristics of PD and multiple system atrophy (MSA), we conducted a large-sample study to investigate the associations between this variant and these two neurodegenerative diseases in a Chinese population. A total of 1216 PD, 406 MSA patients, and 869 healthy controls were included. All cases were genotyped for the Single Nucleotide Polymorphisms (SNP) using Sequenom iPLEX Assay technology. The rs75932628-T variant of the TREM2 gene was not identified in PD patients and controls. The genotype frequency of rs75932628-T SNP in MSA patients was 0.25 % (1/406). However, no significant correlation was identified between this variant and the risk for MSA. TREM2 rs75932628 is unlikely to play a major role in the pathogenesis of these neurodegenerative diseases. Our findings argue against a generalized immune dysfunction triggered by the variant in the TREM2 gene.

The associations between neuropsychiatric symptoms and cognition, frontal lobe function and frontal behavioral changes in the Chinese idiopathic Parkinson's disease (PD) population are largely unknown. This study included 348 idiopathic PD patients from southwest China. Neuropsychiatric symptoms were investigated using the Neuropsychiatric Inventory Questionnaire (NPI), and cognition was assessed using Addenbrooke's Cognitive Examination-Revised (ACE-R). The Frontal Assessment Battery (FAB) was used to evaluate frontal function and the Frontal Behavior Inventory (FBI) was used to assess frontal behavioral changes. The mean (± standard deviation) age of the PD patients was 60.24 ± 12.07 years, and the mean disease duration was 3.88 ± 3.34 years. The mean NPI score was 3.49 ± 4.00. The mean score of ACE-R was 76.82 ± 16.73. The mean score of FAB was 15.27 ± 2.90, and the mean score of FBI was 3.18 ± 5.17. Weak negative correlations between the NPI and ACE-R scores as well as FAB score were found in the total sample, the male patient subgroup, the early onset PD subgroup and the late onset PD subgroup. Strong positive correlations were found between the NPI and FBI scores in the total sample (r=0.661, p

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease, so it is important to explore the survival factors for ALS. Our aim was to evaluate the predictors of survival in Chinese ALS patients. A total of 1049 sporadic ALS patients were enrolled. Kaplan-Meier curves were used to compare survival time. Cox proportional hazards function and the hazard ratio were used to identify adjusted prognostic predictors. Results showed that the mean age of onset was 52.6 ± 12.0 years. During follow-up, 155 patients (14.8%) were lost and 378 patients were deceased. Median survival was 33 months for the deceased patients. In the adjusted Cox proportional hazard model, age of onset, diagnosis delay, rate of disease progression, and non-invasive positive pressure ventilation (NIPPV) treatment had an effect on survival in ALS. In conclusion, our study provides information on survival factors for Chinese ALS patients. Although the onset age of Chinese ALS patients is earlier than that of Caucasian patients, survival factors, including the age of onset, diagnostic delay, rate of disease progression, and NIPPV treatment, are similar.