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The prevalence of sleep disorders and cognitive dysfunction has overwhelmingly increased, with insomnia and Alzheimer’s disease (AD) being the most common form. A multitude of studies have linked the alterations in sleep continuity or sleep architecture with cognitive impairment bilaterally, but the management of disrupted sleep patterns in preclinical AD could be more beneficial since there is no cure for AD. This review mainly focuses on the altered sleep patterns in insomnia, and summarizes potential pathways underlying the relationship between insomnia and cognitive impairment, aiming to establish certain sleep pattern changes as biomarkers for cognitive decline and explore potential therapeutic targets based on evidence from research advances.

EPM2A has been certified as a causative gene in patients with Lafora disease (LD), which is a rare autosomal recessive and severe form of progressive myoclonus epilepsy. LD classically starts in adolescence, characterized by various types of seizure with myoclonic seizure as the main type. Typically within 10 years, intractable seizure attack, rapidly progressing dementia, and a vegetative state were present. LD is particularly frequently found in Mediterranean countries. Here, we report a Chinese family with a novel compound heterozygous mutation in the EPM2A gene, characterized by recurrent vomiting, intractable epilepsy, and progressive cognitive decline.

To describe the clinical and neuroimaging features, treatment response and outcomes of adult myelin oligodendrocyte glycoprotein (MOG) antibody-associated cortical encephalitis.In this retrospective study, adult patients fulling the criteria of encephalitis but not fulfilling those of ADEM and tested positive for serum MOG antibody were recruited from Xiangya Hospital, Central South University (2019-2021). Clinical symptoms, laboratory data, imaging, and outcomes were analyzed.Eleven MOG antibody-associated cortical encephalitis patients consisting of 4 female (36.4%) and 7 male (63.6%) were included with a median onset age of 27 years (ranging: 16-32 years). Fever (8/11), headache (9/11) and seizures (7/11) were the most common symptoms of adult MOG cortical encephalitis, and generalized seizure was the dominant seizure type (4/7). Increased intracranial pressure (5/10, median 280 mm H2O, ranging 240-380 mm H2O), CSF pleocytosis (5/10, median 48 cells/μL, ranging: 18-1800 cells/μL), and protein elevation (4/10, median 0.67 g/L, ranging: 0.46-1.92 g/L) were common. Serum MOG antibody was detected in all patients and the coexistence of CSF NMDAR antibody was found in one case. Imaging showed abnormal brain MRI in 10 patients (90.9%) and 10/10 had the cortical involvement. 8/10 had unilateral lesions while 2/10 had bilateral lesions. 2/10 had the juxta cortical white matter lesions and 2/10 had the corpus callosum lesions. No involvement of deep gray matter or other white matter structure was noted. 5/11 had leptomeningeal and/or lesional enhancements. 10/11 patients had favorable outcomes and 2/11 had clinical relapses with persisting MOG antibody positive during the median follow-up interval of 10 months (ranging: 3-23months).Atypical clinical features for demyelinating diseases including seizures, remarkably increased intracranial pressure, pleocytosis, and protein elevation are common in MOG cortical encephalitis. Involvement of the corpus callosum and cortex around the midline could be unique imaging features of MOG antibody-associated bilateral cortical encephalitis.

Blood circulating microRNAs (miRNAs) are proposed to be promising biomarkers for many neurodegenerative disorders, including Parkinson’s disease (PD). However, there is a lack of identified differentially expressed miRNAs in PD from different studies. The aim of this study was to evaluate miRNAs expression in PD. We measured plasma circulating miRNA expression in three independent sets with a total of 151 PD patients, 21 multiple system atrophy (MSA) patients and 138 healthy controls using high-throughput RT-PCR. We identified that elevated miR-133b and miR-221-3p discriminated early-stage PD from controls with 94.4% sensitivity and 91.1% specificity. Elevated miR-133b and miR-221-3p distinguished PD from controls with 84.8% sensitivity and 88.9% specificity. In addition, miR-4454 distinguished PD from MSA with 57.1% sensitivity and 82.6% specificity. Hence, elevated miR-133b and miR-221-3p potentially represent good biomarkers for early PD, and a combination of miR-133b, miR-221-3p and miR-4454 has the potential to serve as a non-invasive biomarker for PD diagnosis.

Objectives: The epidemiological and clinical characteristics of patients with coronavirus disease 2019 (COVID-19) have been researched. However, the prevalence of repositivity by real-time PCR for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear. Methods: A retrospective study was conducted involving 599 discharged patients with COVID-19 in a single medical centre. The clinical features of patients during their hospitalization and 14-day post-discharge quarantine were collected. Results: A total of 122 patients (20.4%) out of 599 patients retested positive after discharge. Specifically, 94 (15.7%) retested positive within 24 h of discharge, and another 28 patients (4.7%) were repositive on day 7 after discharge, although none showed any clinical symptomatic recurrence. Both repositives and non‑repositives have similar patterns of IgG and IgM. Notably, the length of hospitalization of non-repositive patients was longer than that of 24-h repositive patients and 7-day repositive patients. In addition, the length of hospitalization of 24-h repositive patients was shorter than that of 7-day repositive patients, indicating that the length of hospitalization was also a determinant of viral shedding. Conclusion: Our study provides further information for improving the management of recovered and discharged patients, and further studies should be performed to elucidate the infectiveness of individuals with prolonged or RNA repositivity.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease accompanied with severe paralysis or even death, while the pathogenesis of ALS is still unclear and no effective therapy exists. The accumulating evidence has indicated the association between gut microbiota and various neurological diseases. Thus, to explore the potential role of gut microbiome in ALS, 20 patients diagnosed with probable or definite ALS and 20 healthy controls were enrolled and their fecal excrements were collected. The analysis of fecal community diversity with 16S rDNA sequencing showed an obvious change in microbial structure of ALS patients, where Bacteroidetes at the phylum level and several microbes at the genus level were up-regulated, while Firmicutes at the phylum level and Megamonas at the genus level were down-regulated compared to healthy controls. Additionally, decreased gene function associated with metabolic pathways was observed in ALS patients. The metagenomics further demonstrated the discrepancies in microflora at the species level and relevant metabolites thereof were also revealed when combined with metabolomics. In conclusion, the altered composition of the gut microbiota and metabolic products in ALS patients provided deeper insights into the pathogenesis of ALS, and these biomarkers might be established as potential therapeutic targets which deserve further exploration.

Background: Amyotrophic lateral sclerosis (ALS) is a neurological disorder clinically characterized by motor system dysfunction, with intraneuronal accumulation of the TAR DNAbinding protein 43 (TDP-43) being a pathological hallmark. Riluzole is a primarily prescribed medicine for ALS patients, while its therapeutical efficacy appears limited. TDP-43 transgenic mice are existing animal models for mechanistic/translational research into ALS. Methods: We developed a transgenic rat model of ALS expressing a mutant human TDP-43 transgene (TDP-43M337V) and evaluated the therapeutic effect of Riluzole on this model. Relative to control, rats with TDP-43M337V expression promoted by the neurofilament heavy subunit (NEF) gene or specifically in motor neurons promoted by the choline acetyltransferase (ChAT) gene showed progressive worsening of mobility and grip strength, along with loss of motor neurons, microglial activation, and intraneuronal accumulation of TDP-43 and ubiquitin aggregations in the spinal cord. Results: Compared to vehicle control, intragastric administration of Riluzole (30 mg/kg/d) did not mitigate the behavioral deficits nor alter the neuropathologies in the transgenics. Conclusion: These findings indicate that transgenic rats recapitulate the basic neurological and neuropathological characteristics of human ALS, while Riluzole treatment can not halt the development of the behavioral and histopathological phenotypes in this new transgenic rodent model of ALS.

Novel molecular signatures are needed to improve the early and accurate diagnosis of autism spectrum disorder (ASD), and indicate physicians to provide timely intervention. This study aimed to identify a robust blood non-coding RNA (ncRNA) signature in diagnosing ASD. One hundred eighty six blood samples in the microarray dataset were randomly divided into the training set (n = 112) and validation set (n = 72). Then, the microarray probe expression profile was re-annotated into the expression profile of 4143 ncRNAs though probe sequence mapping. In the training set, least absolute shrinkage and selection operator (LASSO) penalized generalized linear model was adopted to identify the 20-ncRNA signature, and a diagnostic score was calculated for each sample according to the ncRNA expression levels and the model coefficients. The score demonstrated an excellent diagnostic ability for ASD in the training set (area under receiver operating characteristic curve [AUC] = 0.96), validation set (AUC = 0.97) and the overall (AUC = 0.96). Moreover, the blood samples of 23 ASD patients and 23 age- and gender-matched controls were collected as the external validation set, in which the signature also showed a good diagnostic ability for ASD (AUC = 0.96). In subgroup analysis, the signature was also robust when considering the potential confounders of sex, age, and disease subtypes. In comparison with a 55-gene signature deriving from the same dataset, the ncRNA signature showed an obviously better diagnostic ability (AUC: 0.96 vs 0.68, P

Background Mutant transactive response DNA-binding protein (TDP-43) is closely correlated to the inherited form of amyotrophic lateral sclerosis (ALS). TDP-43 transgenic rats can reproduce the core phenotype of ALS and constitutive expression of TDP-43 caused postnatal death. Objective The study aimed to understand whether neurologic deficiency caused by mutant TDP- 43 is dependent on its temporal expression. Method Transgenic rats were established that express mutant human TDP-43 (M337V substitution) in neurons, then a Tet-off system was used to regulate its expression. Results TDP-43 mutant transgenic rats developed significant weakness after the transgene was activated. Rats with expression of mutant TDP-43 at 30 days showed a more aggressive phenotype. More severe pathological changes in neurogenic atrophy were observed in these rats. Conclusion Temporal expression of mutant TDP-43 in neurons promoted serious phenotype in rats. The dysfunction of TDP-43 had a profound impact on the development of motor neurons and skeletal muscles.

Supplemental Digital Content is available in the text, Pioglitazone may have potential benefits in the treatment of cutaneous and metabolic derangements of psoriasis, but its role in the treatment of psoriasis remains in debate. We therefore conducted a meta-analysis to evaluate the clinical efficacy and safety of pioglitazone in psoriasis vulgaris (PsV). We performed a comprehensive search in database of PubMed, Web of Science, Cochrane library, Embase and China National Knowledge Infrastructure (CNKI), and Wan fang database through March 2019 to identify eligible studies. Randomized controlled trials that have evaluated the effect and safety of pioglitazone in PsV were included. Treatment success was defined as ≥75% reduction in psoriasis area and severity index (PASI) score after treatment. Weighted mean differences (WMD), relative risks (RRs) and the corresponding 95% confidence intervals (CIs) were pooled to compare the clinical efficacy and safety between different groups. Six randomized controlled trials (n = 270) were included. Meta-analysis showed that pioglitazone was associated with a remarkable reduction in PASI score in patients with PsV (weight mean difference: 2.68, 95% CI 1.41–3.94, P

Reliable molecular signatures are needed to improve the early and accurate diagnosis of autism spectrum disorder (ASD), and indicate physicians to provide timely intervention. This study aimed to identify a robust blood small nuclear RNA (snRNA) signature in diagnosing ASD. 186 blood samples in the microarray dataset were randomly divided into the training set (n = 112) and validation set (n = 72). Then, the microarray probe expression profiles were re-annotated into the expression profiles of 1253 snRNAs though probe sequence mapping. In the training set, least absolute shrinkage and selection operator (LASSO) penalized generalized linear model was adopted to identify the 9-snRNA signature (RNU1-16P, RNU6-1031P, RNU6-258P, RNU6-335P, RNU6-485P, RNU6-549P, RNU6-98P, RNU6ATAC26P, and RNVU1-15), and a diagnostic score was calculated for each sample according to the snRNA expression levels and the model coefficients. The score demonstrated a good diagnostic ability for ASD in the training set (area under receiver operating characteristic curve (AUC) = 0.90), validation set (AUC = 0.87), and the overall (AUC = 0.88). Moreover, the blood samples of 23 ASD patients and 23 age- and gender-matched controls were collected as the external validation set, in which the signature also showed a good diagnostic ability for ASD (AUC = 0.88). In subgroup analysis, the signature was robust when considering the confounders of gender, age, and disease subtypes, and displayed a significantly better performance among the female and younger cases (P = .039; P = .002). In comparison with a 55-gene signature deriving from the same dataset, the snRNA signature showed a better diagnostic ability (AUC: 0.88 vs 0.80, P = .049). In conclusion, this study identified a novel and robust blood snRNA signature in diagnosing ASD, which might help improve the diagnostic accuracy for ASD in clinical practice. Nevertheless, a large-scale prospective study was needed to validate our results.

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by progressive cognitive decline. It can be divided into familial AD (FAD) and sporadic AD (SAD) based on the family history. Recently dysregulation of cholesterol homeostasis has been implicated in the development of late-onset AD. ATP-binding cassette transporter A7 (ABCA7) gene, regulating the transport of cholesterol, has been recently identified as a susceptible gene of AD by several large genome-wide association studies. To test the genetic effect of ABCA7 rs3764650 on blood lipid levels in Southern Chinese Han population and investigate the risk factors of SAD, a total of 118 SAD patients and 120 healthy matched controls were recruited and the genotyping in ABCA7 rs3764650 was conducted on the Sequenom MassARRAY iPLEX platform. Meanwhile, the levels of fasting lipid profile and mini-mental state examination (MMSE) scores were tested. There was significant difference in genotype distribution between SAD patients and controls (p=0.001). While the difference of ABCA7 rs3764650 allele distribution between SAD patients and controls was only significant in APOEe4-noncarriers (p=0.039). The association between blood lipid levels and ABCA7 rs3764650 genotypes was influenced by APOEe4 status. In APOEe4-noncarriers of SAD, the total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels in GG genotype group were significantly lower than those in GT and TT genotype groups (all p

Paroxysmal kinesigenic dyskinesia (PKD) is characterized by recurrent and brief attacks of dystonia or chorea precipitated by sudden movements. It can be sporadic or familial. Proline-Rich Transmembrane Protein 2 (PRRT2) has been shown to be a common causative gene of PKD. However, less than 50% of patients with primary PKD harbor mutations in PRRT2. The aim of this study is to use eight families with PKD to identify the pathogenic PRRT2 mutations, or possible novel genetic cause of PKD phenotypes. After extensive clinical investigation, direct sequencing and mutation analysis of PRRT2 were performed on patients from eight PKD families. A genome-wide STR and SNP based linkage analysis was performed in one large family that is negative for pathogenic PRRT2 mutations. Using additional polymorphic markers, we identified a novel gene locus on chromosome 3q in this PRRT2-mutation-negative PKD family. The LOD score for the region between markers D3S1314 and D3S1256 is 3.02 and we proposed to designate this locus as Episodic Kinesigenic Dyskinesia (EKD3). Further studies are needed to identify the causative gene within this locus.

Depression has been associated with reduced expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. Genetic association studies of the BDNF Val66Met polymorphism (rs6265) in geriatric depression have produced inconsistent results. A meta-analysis of studies was conducted to compare the frequency of the BDNF Val66Met variant between cases with geriatric depression and age-matched controls. A total of five studies involving 523 cases with geriatric depression and 1,220 psychiatrically healthy controls was included. Met allele carriers had an increased risk for geriatric depression when compared to Val/Val homozygotes (P = 0.004, OR = 1.48, 95% CI = 1.13-1.93). Our findings suggest the BDNF Met allele may confer increased risk for depression as individual age.

Background Schistosoma japonicum is the most widespread schistosoma in the world. Although gastrointestinal system involvement with S japonicum appears to be considerably common, cerebral schistosomiasis is not frequent. Cerebral schistosomiasis japonica intestinal and hepatosplenic involvement is more rare. We collected 2 cases of cerebral schistosomiasis identified by pathological diagnosis, lacking extracranial involvement. In addition, one of them had multiple lesions, which was also rare. Case Description Two male patients came from Dongting Lake region, Hunan province, one of the oldest and most severe endemic areas of China. Their clinical symptoms varied, such as headache, dizziness, seizures, and others. Studies in blood were normal except for eosinophilia. Computed tomography of brains showed hyperdense areas, and MRI showed isointense signal on T1-weighted images, hyperintense signal on T2-weighted images, and heterogeneous enhancement. The definitive diagnosis was cerebral schistosomiasis japonium by biopsy. Standard use of praziquantel and corticosteroid drugs was applied, and the prognosis was good. Conclusion Cerebral schistosomiasis japonica without intestinal and hepatosplenic involvement is exactly rare and easily ignored. The diagnosis sometimes is difficult. Laboratory and imaging examinations are helpful but not specific. Although operation can give the definitive diagnosis, it is not imperative. The administration of praziquantel and corticosteroid drugs in early stages is good for prognosis.

Paroxysmal kinesigenic dyskinesia (PKD) is a rare neurologic inherited disease with heterogeneity. Autosomal dominant (AD) is the common inherited mode. There have been two loci mapped to 16 chromosome for PKD. However, no gene responsible for it has been identified so far. We collected 6 pedigrees from Chinese mainland. There were 122 members in all, including 26 affected. According to New diagnostic criteria of Bruno, they were diagnosed as pure PKD. From the clinic data, we found that the onset age was earlier and the severity was increasing in the subsequent generations in 4 pedigrees of them, which suggested genetic anticipation. Linkage analysis was applied in 2 of these pedigrees. The maximum LOD score and NPL score were negative. The followed haplotypes analysis excluded the PKD locus in both families from chromosome 16, providing evidence for a novel locus.

Summary Aim To assess the efficacy and safety of dipeptidyl peptidase 4-inhibitors (DPP4-I) compared with sulphonylureas in adults with type 2 diabetes (T2D) mellitus. Method Randomised controlled trials were collected from PubMed, EMBASE, Google Scholar and conference. The primary outcome was the change in HbA1c. Secondary outcomes included weight gain, the change in postprandial plasma glucose (PPG), insulin resistance and fasting plasma glucose (FPG), adverse event (AE) and incidence of hypoglycaemia. Results Fourteen studies including 5480 patients randomised to DPP4-I and 5214 patients randomised to sulphonylureas were eligible for the meta-analysis. Compared with sulphonylureas, DPP4-I were associated with a smaller decline in HbA1c (WMD, weighted mean differences 0.08%, 95% CI: 0.03–0.14, p = 0.001), and resulted in weight loss of 1.945 kg (95% CI: −2.237 to −1.653, p < 0.0001). The effect of DPP4-I lowering FPG was inferior to that of sulfonylureas (WMD, 0.268 mmol/l, 95% CI, 0.151–0.385, p < 0.0001), and similar in reducing PPG (WMD, 0.084, 95% CI, −0.701 to 0.869, p = 0.833). According to the follow-up period, the included trials were separated into three groups (group 1: less than half one year, group 2: from half one year to 1 year, group 3: more than 1 year). Subgroup analysis showed that the difference in HbA1c between DPP4-I and sulphonylureas presented a decline curve (group 1: 0.50, 95% CI: 0.15–0.84, group 2: 0.05, 95% CI: −0.05 to 0.15, group 3: 0.09, 95% CI: 0.03–0.15). DPP4-I had a favourable insulin resistance compared with sulfonylureas (WMD, −0.673, 95% CI, −1.248 to −0.097, p = 0.022). In addition, compared with sulfonylureas, DPP4-I was associated with a decrease in overall risk for AE (RR, 0.93, 95% CI, 0.91–0.96, p < 0.0001). The incidence of hypoglycaemia was lower with DPP4-I (RR, 0.24, 95% CI, 0.21–0.27, p < 0.001). Conclusion Patients with T2D who receive DPP4-I could achieve almost similar glycaemic targets with sulphonylureas, with favourable effects on body weight and lower incidence of hypoglycaemia.

Summary Background and aims Tenuigenin (Ten) is a Chinese herbal extract with antioxidative and antiinflammatory effects on toxin-induced cell models of Parkinson's disease (PD); however, its effects on α-synuclein toxicity-based PD models remain unknown. α-synuclein hyperphosphorylation is a key event in PD pathogenesis and potential target of therapeutic interventions. We tested whether Ten alleviates α-synuclein-induced cytotoxicity via reducing kinases that phosphorylate α-synuclein. Methods SH-SY5Y cells transiently transfected with wild-type or A53T mutant α-synuclein were used to evaluate the effect of Ten on the levels of α-synuclein phosphorylation-related kinases. Cells treated with 10 μM Ten for 24 h were measured for viability (proliferation and apoptosis assays) and cellular proteins harvested and fractioned. The levels of total and phosphorylated α-synuclein and five associated kinases (polo-like kinase [PLK] 1–3, casein kinase [CK] 1–2) were evaluated by Western blotting. Results Overexpression of either wild-type or A53T mutant α-synuclein decreased cell viability and increased α-synuclein phosphorylation. Ten treatment-protected cells from this α-synuclein-induced toxicity and dramatically reduced α-synuclein phosphorylation and PLK3 (but not other kinase) levels. Conclusion In α-synuclein cell model of PD, Ten is effective in attenuating α-synuclein-induced toxicity and α-synuclein phosphorylation probably via targeting PLK3, suggesting it could be an efficient therapeutic drug to treat α-synuclein-related neurodegeneration.

Lewy bodies are made from insoluble, phosphorylated α-synuclein, but the earliest changes that precipitate such pathology still remain conjecture. In this study, we quantify and identify relationships between the levels of the main pathologic form of phosphorylated α-synuclein over the course of Parkinson’s disease in regions affected early through to end-stage disease. Brain tissue samples from 33 cases at different disease stages and 13 controls were collected through the Australian Network of Brain Banks. 500 mg of frozen putamen (affected preclinically) and frontal cortex (affected late) was homogenized, fractionated and α-synuclein levels evaluated using specific antibodies (syn-1, BD Transduction Laboratories; S129P phospho-α-synuclein, Elan Pharmaceuticals) and quantitative western blotting. Statistical analyses assessed the relationship between the different forms of α-synuclein, compared levels between groups, and determined any changes over the disease course. Soluble S129P was detected in controls with higher levels in putamen compared with frontal cortex. In contrast, insoluble α-synuclein occurred in Parkinson’s disease with a significant increase in soluble and lipid-associated S129P, and a decrease in soluble frontal α-synuclein over the disease course. Increasing soluble S129P in the putamen correlated with increasing S129P in other fractions and regions. These data show that soluble non-phosphorylated α-synuclein decreases over the course of Parkinson’s disease, becoming increasingly phosphorylated and insoluble. The finding that S129P α-synuclein normally occurs in vulnerable brain regions, and in Parkinson’s disease has the strongest relationships to the pathogenic forms of α-synuclein in other brain regions, suggests a propagating role for putamenal phospho-α-synuclein in disease pathogenesis.