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Chengxiang Yuan,1,* Siyan Chen,1,* Yiting Ruan,1 Yuntao Liu,1 Haoran Cheng,1 Yaying Zeng,1 Yunbin Chen,1 Qianqian Cheng,2 Guiqian Huang,1 Weilei He,1 Jincai He1 1Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People’s Republic of China; 2School of Mental Health, Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jincai HeDepartment of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, People’s Republic of ChinaTel/Fax +86 0577 55579363Email hjc@wmu.edu.cnBackground: Hemorrhagic transformation (HT) is a severe complication occurring in acute ischemic stroke (AIS) patients. Stress hyperglycemia is frequent in patients with acute illness such as stroke. We aimed to explore the association between stress hyperglycemia and HT in AIS patients.Methods: A total of 287 consecutive participants with HT and 285 age- and sex-matched stroke patients without HT were enrolled in this study. Baseline glucose and glycated hemoglobin (HbA1c) levels were collected to measure stress hyperglycemia. The stress hyperglycemia ratio (SHR) was calculated by dividing the fasting plasma glucose at admission with HbA1c. HT was diagnosed by follow-up imaging assessment, and was radiologically classified as hemorrhagic infarction type (HI) 1 or 2 or parenchymal hematoma type (PH) 1 or 2.Results: Univariate analysis showed that SHR is significantly higher among patients with HT than those without HT. Compared to the patients in the lower three quartiles of SHR, the incidence of HT was significantly higher among patients with the highest quartile of SHR in total population, diabetic and non-diabetic population. We also observed that patients with the highest SHR quartile were associated with an increased risk of hemorrhagic transformation after adjusted for potential covariates (68.4% versus 39.1%; adjusted odds ratio, 2.320; 95% confidence interval, 1.207– 4.459; P=0.012).Conclusion: The stress hyperglycemia ratio, representing the state of stress hyperglycemia, was significantly associated with an increased risk of hemorrhagic transformation in patients with acute ischemic stroke.Keywords: hyperglycemia, hemorrhagic transformation, acute ischemic stroke, stress hyperglycemia

The stability of the intestinal microenvironment is the basis for maintaining the normal physiological activities of the intestine. On the contrary, disordered dynamic processes lead to chronic inflammation and disease pathology. Pinus massoniana pollen polysaccharide (PPPS), isolated from Taishan Pinus massoniana pollen, has been reported with extensive biological activities, including immune regulation. However, the role of PPPS in the intestinal microenvironment and intestinal diseases is still unknown. In this work, we initiated our investigation by using 16S rRNA high-throughput sequencing technology to assess the effect of PPPS on gut microbiota in mice. The result showed that PPPS regulated the composition of gut microbiota in mice and increased the proportion of probiotics. Subsequently, we established immunosuppressive mice using cyclophosphamide (CTX) and found that PPPS regulated the immunosuppressive state of lymphocytes in Peyer's patches (PPs). Moreover, PPPS also regulated systemic immunity by acting on intestinal PPs. PPPS alleviated lipopolysaccharide (LPS) -induced Caco2 cell damage, indicating that PPPS has the ability to reduce the damage and effectively improve the barrier dysfunction in Caco2 cells. In addition, PPPS alleviated colonic injury and relieved colitis symptoms in dextran sodium sulfate (DSS)-induced colitis mice. Overall, our findings indicate that PPPS shows a practical regulatory effect in the intestinal microenvironment, which provides an essential theoretical basis for us to develop the potential application value of PPPS further.

At present, most studies on the relationship between hepatitis B virus (HBV) and IL-33/ST2 axis focus on clinical detection, but the underlying molecular mechanisms of HBx and IL-33/ST2 axis regulation and Th cell function regulation have not been explored. In this study, serum samples of patients with chronic hepatitis B (CHB) and HBV-related liver cancer (HBV-HCC), and healthy controls, as well as the supernatant solutions of HL7702-WT, HL7702-NC, and HL7702-HBx cells were collected to detect the content of soluble ST2 (sST2). The contents of Th1 cytokines (TNF-α and TNF-γ) and Th2 cytokines (IL-6 and IL-10) in the supernatant of different co-culture groups were detected. The effects of GATA2 on ST2 promoter transcription were investigated by upregulation or interference with GATA2 expression, dual-luciferase reporting, and ChIP experiments. The combined detection of sST2 and FIB-4 was beneficial to the non-invasive diagnosis of liver fibrosis. HBx promotes sST2 expression in liver cells, upregulates Th2 cell function, and inhibits Th1 cell function through IL-33/ST2 axis. HBx interacts with GATA2 to influence the activity of ST2 promoter. Serum sST2 detection is an invaluable indicator for the assessment of the progress of HBV infectious diseases, and the IL-33/ST2 axis plays an important role in changing the cellular immune function caused by HBV infection.

Background:Stroke-associated pneumonia (SAP) is one of the common complications of stroke patients. Higher lactic dehydrogenase (LDH) and lower albumin levels were associated with SAP, but the contribution of the LDH to albumin ratio (LAR) to the risk of SAP in acute ischemic stroke (AIS) patients remained unclear.Methods:A total of 3173 AIS patients were included in this study, divided into SAP (n= 417) and non-SAP groups (n= 2756). Characteristics were compared between these two groups. The receiver operating characteristic curves (ROC) were used to evaluate the discrimination ability of the LAR, LDH, and albumin levels in predicting SAP. Logistic regression analysis was furtherly adopted to estimate the association between LAR and SAP. We also used the restricted cubic spline (RCS) to clarify the relationship between LAR and the risk of SAP.Results:LAR in the SAP group was significantly higher than that of the non-SAP group (8.75 ± 4.58 vs. 6.10 ± 2.55,P< 0.001). According to the results of ROC, LAR had the highest prognostic accuracy compared to LDH and albumin (P< 0.05). Besides, the logistic regression model showed that higher LAR (LAR > 6.75) were more vulnerable to SAP (OR, 2.80; 95% CI, 2.18–3.59,P< 0.001), controlling the confounders. The RCS model showed that there was a non-linear relationship between LAR and the risk of SAP.Conclusion:High LAR was associated with an increased risk of SAP in patients with AIS. LAR may be a potential predictor for the incidence of SAP. Appropriate prevention measures were needed in patients with high LAR (LAR > 6.75).

Objective: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an acute form of encephalitis of autoimmune etiology. We aimed to evaluate the risk factors that predicted the need for mechanical ventilation during the acute phase of anti-NMDAR encephalitis through an analysis of the clinical characteristics and biochemical test results of the patients with anti-NMDAR encephalitis.Methods: In this retrospective study, patients who primarily presented with anti-NMDAR encephalitis and exhibited anti-NMDAR antibody positivity in the cerebrospinal fluid (CSF) between November 2015 and February 2020 were included. Data on the clinical characteristics, biochemical test results, and treatment methods selected for the patients were collected for the analysis of factors predicting the need for mechanical ventilation.Results: Thirty-one patients with a median age of onset of 31 years (inter-quartile range: 21–48 years) were included in this study, of which 15 were male (48.4%). Psychosis (23, 74.2%), seizures (20, 64.5%), and memory deficit (20, 64.5%) were the most common clinical manifestations. At admission, 17 patients (54.8%) presented with pyrexia, of which 12 (38.7%) had a body temperature ≥38°C, and six patients (19.4%) presented with central hypoventilation. All patients received first-line therapy (glucocorticoids, intravenous immunoglobulin, or plasmapheresis alone or combined), whereas two patients (6.5%) received rituximab, a second-line agent, as well. Seven patents required mechanical ventilation. Results of univariate logistic regression analysis revealed that body temperature ≥38°C [odds ratio (OR) = 18, 95% confidence interval (CI): 1.79–181.31, P < 0.05] and central hypoventilation at admission (OR = 57.50, 95% CI: 4.32–764.89, P < 0.05) were the risk factors for mechanical ventilation. Multivariate logistic regression analysis showed that central hypoventilation at admission was the only risk factor predicting the need for mechanical ventilation.Conclusion: Central hypoventilation at admission is a key risk factor for mechanical ventilation during hospitalization in patients with anti-NMDAR encephalitis.

Objectives: To describe the incidence, predictors, and clinical impact of permanent pacemaker insertion (PPI) following transcatheter aortic valve replacement (TAVR) in women. Background: Data on pacemaker insertion complicating TAVR in women are scarce. Methods: The Women's International Transcatheter Aortic Valve implantation (WIN-TAVI) is a prospective registry evaluating the safety and efficacy of TAVR in women. We included patients without preprocedural pacemakers and divided them into two groups: (1) PPI and (2) no-PPI. We identified PPI predictors using logistic regression and studied its clinical impact on the Valve Academic Research Consortium (VARC)-2 efficacy and safety endpoints. Results: Out of 1019 patients, 922 were included in the analysis. Post-TAVR PPI occurred in 132 (14.3%) patients. Clinical and procedural characteristics were similar in both groups. Pre-existing right bundle branch block (RBBB) was associated with a high risk of post-TAVR PPI (OR 3.62, 95% CI 1.85–7.06, p < 0.001), while implantation of balloon-expandable prosthesis was associated with a lower risk (OR 0.47, 95% CI 0.30–0.74, p < 0.001). Post-TAVR PPI prolonged in-hospital stay by a median of 2 days (11 [9–16] days in PPI vs. 9 [7–14] days in no-PPI, p = 0.005), yet risks of VARC-2 efficacy and safety endpoints at 1 year were similar in both groups (adjHR 0.95, 95% CI 0.60–1.52, p = 0.84 and adjHR 1.22, 95% CI 0.83–1.79, p = 0.31, respectively). Conclusion: Pacemaker implantation following TAVR is frequent among women and is associated with pre-existing RBBB and valve type. PPI prolongs hospital stay, albeit without any significant impact on 1-year outcomes.

The association between hemoglobin A1c (HbA1c) and clinical outcomes of acute ischemic stroke is uncertain. We aimed to evaluate the association between initial hemoglobin A1c level and clinical outcome after acute ischemic stroke.A total of 408 patients with first-ever acute ischemic stroke were included in this study. We divided the patients into three groups according to HbA1c level: low HbA1c level (HbA1c5.7%), moderate HbA1c level (HbA1c 5.7-6.4%), and high HbA1c level (HbA1c ≥6.5%). Poor neurological outcomes were defined as modified Rankin Scale (mRS) score of 2-6 at 3 months after stroke. The relation between HbA1c value and clinical outcomes were evaluated by using multivariate logistic regression analyses.Moderate HbA1c level was present in 126 (30.9%) patients and high HbA1c level in 129 (31.6%) patients. After adjustment for potential confounding variables, both patients in the high HbA1c level group (adjusted odds ratio [OR]: 2.387; 95% confidence interval [CI], 1.201-4.745; P = .013) and moderate HbA1c level group (adjusted OR: 1.797; 95% CI, 1.005-3.214; P = .048) had a significantly higher poor neurological outcomes than the group in the low HbA1c level. When separately analyzed according to with or without diabetes, the HbA1c level as continuous variable was also associated with poor functional outcome at 3 months in the diabetic patients (adjusted OR: 1.482, 95% CI, 1.013-2.167, P = .042), nor in nondiabetic group.Higher HbA1c on admission was an independent predictor of adverse functional outcome in ischemic stroke patients. Based on this point, tight glycemic control must be necessary for high-risk diabetic patients.

Gender-specific differences were found in serum uric acid (SUA) levels and the risk of isolated distal deep vein thrombosis (IDDVT). This study aimed to explore the association among gender, SUA, and IDDVT in stroke patients.Finally, 3404 patients were recruited and divided into two groups: IDDVT (n = 1233) and Non-IDDVT (n = 2171) groups. Propensity score matching (PSM) was conducted to match the patients. Binary logistic regression was adopted to explore the association between SUA and IDDVT, with the SUA divided into quartiles. After PSM, 975 patients were included in each group. Non-IDDVT group had a larger proportion of male than IDDVT group (64.9% vs. 52.7%, p 0.001). Moreover, males showed higher SUA levels than females (316.7 ± 102.1 vs. 261.8 ± 94.0 μmol/L, t = 12.1, p 0.001). The highest quartile of SUA (≥346 μmol/L) showed a lower risk of IDDVT (OR = 0.629, p = 0.001), while the lowest quartile (≤225 μmol/L) showed a higher risk of IDDVT (OR = 1.361, p = 0.022).In patients with stroke, SUA played a protective role in IDDVT. Females had a higher risk of IDDVT, which may be owing to the lower SUA levels than males. In clinical practice, more attention should be paid to the risk of IDDVT in females, especially those with lower SUA levels.

Mounting evidence suggests that mitochondrial dysfunction and impaired mitophagy lead to Parkinson's disease (PD). Quercetin, one of the most abundant polyphenolic flavonoids, displays many health-promoting biological effects in many diseases. We explored the neuroprotective effect of quercetin in vivo in the 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD and in vitro in 6-OHDA-treated PC12 cells. In vitro, we found that quercetin (20 μM) treatment improved mitochondrial quality control, reduced oxidative stress, increased the levels of the mitophagy markers PINK1 and Parkin and decreased α-synuclein protein expression in 6-OHDA-treated PC12 cells. Moreover, our in vivo findings demonstrated that administration of quercetin also relieved 6-OHDA-induced progressive PD-like motor behaviors, mitigated neuronal death and reduced mitochondrial damage and α-synuclein accumulation in PD rats. Furthermore, the neuroprotective effect of quercetin was suppressed by knockdown of either Pink1 or Parkin.

Objective To explore whether poor sleep is associated with post‐stroke anxiety (PSA) in Chinese patients with acute ischemic stroke (AIS) and to verify whether poor sleep is a predictor of PSA. Methods A total of 327 patients with AIS were enrolled and followed up for 1 month. Sleep quality within 1 month before stroke was evaluated using the Pittsburgh Sleep Quality Index (PSQI) at admission. The patients were divided into the poor sleep group (PSQI > 7, n = 76) and good sleep group (PSQI ≤ 7, n = 251). One month after stroke, patients with obvious anxiety symptoms and a Hamilton Anxiety Scale score >7 were diagnosed with PSA. Results Eighty‐seven patients (26.6%) were diagnosed with PSA. Compared to the good sleep quality group, the incidence of PSA in patients with poor sleep quality was higher (42.1% vs. 21.9%, p = .001). Poor sleep quality is more common in patients with PSA (35.6% vs. 18.8%, p = .001). A logistic regression analysis indicated that poor sleep quality was significantly associated with PSA (OR: 2.265, 95% CI: 1.262–4.067, p = .003). After adjusting for conventional and identified risk factors, poor sleep quality was found to be independently associated with PSA (OR: 2.676, 95% CI: 1.451–4.936, p = .001). Conclusions Poor sleep quality before stroke was associated with PSA and may be an independent risk factor of PSA 1 month after AIS onset., We found that the incidence rate of poor sleep quality is significantly higher in PSA patients than in non‐PSA patients. Poor sleep quality before stroke is independently associated with the development of PSA, even after adjustment for several conventional confounders. These findings suggested poor sleep quality before stroke could provide important predictive information for anxiety after acute ischemic stroke.

While machine learning approaches to analyzing Alzheimer disease connectome neuroimaging data have been studied, many have limited ability to provide insight in individual patterns of disease and lack the ability to provide actionable information about where in the brain a specific patient's disease is located. We studied a cohort of patients with Alzheimer disease who underwent resting state functional magnetic resonance imaging and diffusion tractography imaging. These images were processed, and a structural and functional connectivity matrix was generated using the HCP cortical and subcortical atlas. By generating a machine learning model, individual-level structural and functional anomalies detection and characterization were explored in this study. Our study found that structural disease burden in Alzheimer's patients is mainly focused in the subcortical structures and the Default mode network (DMN). Interestingly, functional anomalies were less consistent between individuals and less common in general in these patients. More intriguing was that some structural anomalies were noted in all patients in the study, namely a reduction in fibers involving parcellations in the right anterior cingulate. Alternately, the functional consequences of connectivity loss were cortical and variable. Integrated structural/functional connectomics might provide a useful tool for assessing AD progression, while few concerns have been made for analyzing the mismatch between these two. We performed a preliminary exploration into a set of Alzheimer disease data, intending to improve a personalized approach to understanding individual connectomes in an actionable manner. Specifically, we found that there were consistent patterns of white matter fiber loss, mainly focused around the DMN and deep subcortical structures, which were present in nearly all patients with clinical AD. Functional magnetic resonance imaging shows abnormal functional connectivity different within the patients, which may be used as the individual target for further therapeutic strategies making, like non-invasive stimulation technology.

Background and Purpose: According to previous studies, the mean platelet volume-to-lymphocyte ratio (MPVLR) represents a novel marker of a poor short-term prognosis in patients with a myocardial infarction who underwent primary percutaneous coronary intervention. We aimed to evaluate the association between MPVLR and clinical outcomes of patients with acute ischemic stroke who were treated with intravenous thrombolysis.Methods: Two hundred forty-one patients with ischemic stroke receiving intravenous thrombolysis were prospectively enrolled in this study. Blood samples for MPVLR were obtained at admission and at 18–24 h after treatment with intravenous thrombolysis. A poor functional outcome was defined as a modified Rankin scale score of 3–6 at 3 months after stroke.Results: At admission, the area under the curve of MPVLR to predict poor functional outcomes at 3 months was 0.613 [95% confidence interval (CI), 0.541–0.686; P = 0.003), and the best predictive MPVLR value was 5.8. Patients with an MPVLR ≥5.8 had a 3.141-fold increased risk of a poor outcome at 3 months (95% CI, 1.491–6.615; P = 0.003) compared to patients with an MPVLR

OBJECTIVE It is unknown whether prediabetes is a predictor of poststroke depression (PSD). We aimed to explore the relationship between prediabetes and PSD in Chinese patients with acute ischemic stroke. METHODS This is a prospective cohort study, and a total of 358 patients with acute ischemic stroke were recruited and enrolled. Patients were divided into 3 groups: normal glucose group (NGT, n = 96), prediabetes group (preDM, n = 134, impaired fasting glucose (IFG), and/or impaired glucose tolerance (IGT) and/or HbA1c (A1c) 5.7%-6.4%), and the diabetes mellitus group (DM, n = 128). At 1 month after stroke, patients with a Hamilton Depression Scale score of ≥8 were diagnosed as PSD. RESULTS In post hoc comparisons, the risk of PSD in patients with diabetes and prediabetes was higher than patients with NGT (37.5% vs 31.3% vs 14.6%, P = .001). Compared with NGT, the incidence rate of PSD in patients with prediabetes with HbA1c 5.7% to 6.4% and patients with prediabetes with IFG/IGT + HbA1c 5.7% to 6.4% was higher (35.3% vs 14.6%, 38.0% vs 14.6%; P = .006; P = .003, respectively). In logistic regression, prediabetes with HbA1c 5.7% to 6.4% and prediabetes with IFG/IGT + HbA1c 5.7% to 6.4% were a significant independent predictor of PSD after adjusting for potential confounding factors, with odd ratios of 1.731 and 1.978, respectively. CONCLUSIONS Our study showed that prediabetes was associated with PSD and may predict its development at 1 month poststroke. In prediabetes subgroups, patients with HbA1c 5.7% to 6.4% were more likely to develop PSD compared to NGT and IFG/IGT groups.

A genome-wide association study (GWAS) reported that the single nucleotide polymorphism (SNP) rs4618210 in the PLCL2 gene is related to myocardial infarction (MI) in the Japanese population, but no study has examined the correlation of PLCL2 with ischemic stroke (IS). The present study was designed to investigate whether the genetic variation in PLCL2 is associated with large artery atherosclerotic (LAA) stroke in a Han Chinese population. Tagging SNPs (tSNPs) of the PLCL2 gene were determined by a fine-mapping strategy and were genotyped by improved multiplex ligation detection reaction (iMLDR) technology in 669 LAA stroke patients and 668 healthy controls. A logistic regression model was used to analyze the associations between genetic variation at PLCL2 and the risk of LAA stroke. Two SNPs were significantly associated with the risk of LAA stroke after adjusting for potential confounders: for rs4685423, the AA genotype and CA genotype decreased the risk of LAA stroke compared with the CC genotype (multivariate-adjusted, P = 0.001); for rs4618210, the AA genotype and GA genotype decreased the risk of LAA stroke compared with the GG genotype (multivariate-adjusted, P = 0.007). In addition, haplotype analysis indicated that compared with haplotype TTT, haplotype TAT decreased the risk of LAA stroke in block 2 (adjusted OR, 0.706; 95% CI, 0.550–0.907; P = 0.006). The analysis of SNP–SNP interactions showed that rs4685423 was the most influential contributor to LAA stroke risk. SNPs rs4685423 and rs4618210 in the PLCL2 gene may be related to the risk of LAA stroke in Han Chinese.

Prolonged pulsatile administration of Levodopa (L-dopa) can generate L-dopa–induced dyskinesia (LID). Numerous studies have shown that continuous dopamine delivery (CDD) was helpful in reducing the expression of LID. 6-OHDA lesioned rats were randomly divided into two groups to receive intermittent L-dopa stimulation (L-dopa/benserazide) or Levodopa/benserazide PLGA microsphere (LBPM) for 3 weeks. rAAV (recombinant adeno-associated virus) vector were used to overexpress and ablation of β-arrestin2. We found that LBPM developed less AIM severity compared with standard L-dopa administration, whereas selective deletion of β-arrestin2 in striatum neurons dramatically enhanced the severity of dyskinesia by LBPM. On the contrary, the effects of LBPM in terms of ALO AIM was further relieved by β-arrestin2 overexpression. Furthermore, no significant change in motor behavior were seen neither in inhibition nor overexpression of β-arrestin2. In short, our experiments provided evidence that LBPM prevented LID behavior was likely to through β-arrestin2, suggesting that a therapy modulating β-arrestin2 may provide a more effective anti-dyskinetic approach with a low risk of untoward effects.

Objective: Patients with poor-grade aneurysm subarachnoid hemorrhage (SAH) have commonly been considered to have a poor prognosis. The objective of this study was to investigate the independent risk factors affecting clinical outcomes in intracranial aneurysm patients with poor-grade aneurysm subarachnoid hemorrhage (aSAH) underwent different intervention therapies. Methods: A multicenter observational registry of 324 poor-grade aSAH patients treated at tertiary referral centers from October 2010 to March 2012 were enrolled in this study. The clinical data including patient characteristics on admission and during treatment course, treatment modality, aneurysm size and location, radiologic features, signs of cerebral herniation (dilated pupils), and functional neurologic outcome were collected. Clinical outcomes were assessed via a modified Rankin Scale at 12 months. Multivariate logistic regression models were used to develop prognostic models. The area under the receiver operator characteristic curves (AUC) and Hosmer-Lemeshow tests were used to assess discrimination and calibration. WAP score was developed to predict risk of poor outcome. Results: Older age, female gender, ventilated breathing status, non-reactive pupil response, pupil dilation, lower GCS score, a WFNS grade of V, intraventricular hemorrhage, a higher Fisher grade, a higher modified Fisher grade, and conservative treatment were calculated to be associated with a relatively poor outcome. Multivariate analyses revealed that older age, lower Glasgow coma scale score (GCS), the absence of pupillary reactivity, higher modified Fisher grade, and conservative treatment were independent predictors of poor outcome, showed good discrimination and calibration. Patients with WFNS grade V, older age and non-reactive pupillary reactivity were predicted to have a poor outcome by WAP risk score. Conclusions: A simple WAP risk score had good discrimination and calibration in the prediction of outcome. The risk score can be easily measured and may complement treatment decision-making.

Objective: To describe the clinical features, laboratory data, treatment, and outcomes of anti-N-methyl-D-aspartate (NMDAR) encephalitis in Chinese patients. Methods: This retrospective study included hospitalized patients definitively diagnosed with anti-NMDAR encephalitis and positive for anti-NMDAR antibodies in the cerebrospinal fluid (CSF) in Shenzhen People's hospital, between November 2015 and February 2020. The clinical manifestation, laboratory data, treatments and outcomes were collected retrospectively. Patients were followed up for more than 1 year. Results: The study included 31 patients (15 men, 48.4%) with a median age of 31 years (interquartile range 21-48). The most common clinical presentations were psychosis (n = 23, 74.2%), seizures (n = 20, 64.5%), and memory impairment (n = 20, 64.5%). Total magnetic resonance imaging abnormalities were found in 11 patients (35.5%), with the medial temporal and frontal lobes as the most commonly involved. Abnormal electroencephalogram was observed in 16 patients (51.6%). Five out of 31 patients (19.5%) were diagnosed as neoplasm, including five females with ovarian teratoma and one male with a central nervous system tumor. Multiple immune antibodies, including anti-SSA antibody in four patients (15.4%), anti-Ro52 antibody in four (15.4%), antinuclear antibody (ANT) in four (15.4%), anti-thyroglobulin antibodies (TGAb) in five (17.2%), and thyroid peroxidase antibodies (TPOAb) in three (10.3%) were present. All patients received first-line immunization therapy (intravenous immunoglobulin, glucocorticoids, or plasmapheresis alone or combined), and only two patients (7.3%) received second-line immunization therapy (rituximab). Mechanical ventilation was more necessary in women (37.5%) than in men (6.7%) (p = 0.04), and 29 (93.5%) had favorable clinical outcomes. At more than 12 months of follow-up, the median modified Rankin Scale score decreased from 4 to 0. Conclusions: Patients with anti-NMDAR encephalitis in China had high rates of psychosis and seizures, with low rates of underlying neoplasms. A higher proportion of female patients required mechanical ventilation. Complications with other positive autoimmune antibodies were a common clinical symptoms of anti-NMDAR encephalitis. Majority of the patients obtained satisfactory outcomes in combination with early first-line and long-term immunization therapy.

Alzheimer’s disease (AD) is the most common cause of dementia in elderly that serves to be a formidable socio-economic and healthcare challenge in the 21st century. Mitochondrial dysfunction and impairment of mitochondrial-specific autophagy, namely mitophagy, have emerged as important components of the cellular processes contributing to the development of AD pathologies, namely amyloid-β plaques (Aβ) and neurofibrillary tangles (NFT). Here, we highlight the recent advances in the association between impaired mitophagy and AD, as well as delineate the potential underlying mechanisms. Furthermore, we conduct a systematic review the current status of mitophagy modulators and analyzed their relevant mechanisms, evaluating on their advantages, limitations and current applications in clinical trials for AD patients. Finally, we describe how deep learning may be a promising method to rapid and efficient discovery of mitophagy inducers as well as general guidance for the workflow of the process.

Objective To prospectively evaluate the effect of morning blood pressure peak (MBPP) on early progressive ischemic stroke (EPIS). Patients and Methods A total of 135 patients with acute ischemic stroke were enrolled and completed all assessments. The patients were divided into EPIS group and non-EPIS group, with 22 and 113 cases in each group, respectively, according to the assessment of Scandinavian stroke scale within three days after onset. All cases received conventional treatment for stroke and its risk factors. 24 -h dynamic blood pressure monitoring was performed within 24 h after admission. Based on the 24 -h mean blood pressure, MBPP, morning blood pressure, and other risk factors for EPIS, we conducted a logistic regression analysis to evaluate whether MBPP was an independent risk factor for EPIS. Results Mean systolic blood pressure, systolic and diastolic MBPP, morning systolic and diastolic blood pressure were all significantly higher in EPIS group than in non-EPIS group (p = 0.037, p = 0.001, p = 0.035, p = 0.003, p = 0.042, respectively). Logistic regression analysis showed that MBPP was an independent risk factor for EPIS (OR = 1.057, 95% CI 1.014–1.102, p = 0.009). Further stratified analysis showed that incidences of EPIS in patients with elevated MBPP combined with large artery atherosclerosis or small artery occlusion were comparable (41.2% vs. 25.0%, p = 0.367), and the systolic MBPP was significantly higher in morning EPIS group than in non-morning EPIS group (p = 0.041). Conclusion Elevated systolic MBPP might be an independent risk factor for EPIS, and play a more obvious effect on EPIS manifesting in the morning especially.

Background To investigated distinct manifestations of Sjögren’s syndrome (SS) patients with neurological complications and the potential risk factors associated with neurological complications in SS, and to produce a disease evaluation and neurological involvement prediction for SS. Methods 566 patients who fulfilled the 2002 classification criteria for SS from the Rheumatology Department of the First Affiliated Hospital of Wenzhou Medical University were included in the cross-sectional study. Clinical, immunological and histological characteristics were surveyed, and potential risk factors for neurological complications were examined by multivariate analysis. Results Among 566 SS patients, 184 (32.5%) patients had neurological involvement, with more than 10% got limbs pain, limbs numbness and cerebral infarction, respectively. Of these 184 SS patients with neurological complications, secondary SS (sSS) patients had a higher prevalence of peripheral nervous system (PNS) involvement than primary SS (pSS) patients (31.1 vs. 19%). And sSS patients showed higher total ESSPRI score and higher prevalence of xerostomia and low C3, C4 levels with more liver, articular involvement and saliva gland atrophy, and more severe lymphocyte infiltration in salivary glands than pSS patients. As for the specific factors associated with neurological involvement, low C3 level were found to be significant in pSS or sSS patients who were younger 50 year old, and ANA positivity, cardiac involvement, saliva gland atrophy were demonstrated to be associated in elder pSS patients. And xerophthalmia was found to be associated in sSS patients. Conclusion Low complement (C3) levels, xerophthalmia, ANA positive, cardiac involvement and labial salivary gland histological result were good ways to predict neurological complications in different subgroups of SS, which might provide insight into better clinical decision-making, especially at early stages of the disease.

Objective To evaluate the effect of fluoxetine on three-year recurrence rate of acute ischemic stroke. Patients and Methods 404 enrolled patients with acute ischemic stroke were randomly divided into control and treatment groups, and underwent conventional secondary preventive therapy for ischemic stroke. In addition, the treatment group was administered fluoxetine (20 mg daily for 90 days). A three-year follow-up was performed, and indicators related to risk factors of stroke were assessed at day 90 of follow-up. The effect of fluoxetine on the three-year recurrence rate of acute ischemic stroke was evaluated by survival analysis, as well as multifactor Cox regression analysis. Results The values of systolic blood pressure, blood total cholesterol, blood low density lipoprotein and glycosylated hemoglobin at day 90 of follow-up were significantly lower in treatment group than control group (P = 0.002, P = 0.002, P = 0.018, P = 0.011, respectively). The occurrence rates of epilepsy, gastrointestinal bleeding, syncope, allergic reactions, hemorrhagic infarction, and death were not significantly different between the two groups during the follow-up (P > 0.05). The recurrence-free survival rate of ischemic stroke was significantly lower in the treatment group than control group as assessed by the Kaplan-Meier test (85.1% Vs 75.7%, P = 0.016), as well as the recurrence-free survival rate after day 90 in the three-year follow-up (87.0% Vs 79.3%, P = 0.043). Multifactor Cox regression analysis demonstrated treatment with fluoxetine was an independent factor reducing three-year recurrence in acute ischemic stroke (HR = 0.594, 95% CI: 0.376–0.938). Conclusion Treatment with fluoxetine for 90 days after acute ischemic stroke significantly reduces the three-year recurrence rate of ischemic stroke.

Backgrounds Long non-coding RNA (LncRNA) have been reported to be involved in the pathogenesis of neurodegenerative diseases, but whether it can serve as a biomarker for Alzheimer disease (AD) is not yet known. Methods The present study selected four specific LncRNA (17A, 51A, BACE1 and BC200) as possible AD biomarker. RT-qPCR was performed to validate the LncRNA. Receiver operating characteristic curve (ROC) and area under the ROC curve (AUC) were applied to study the potential of LncRNA as a biomarker in a population of 88 AD patients and 72 control individuals. Results We found that the plasma LncRNA BACE1 level of AD patients was significantly higher than that of healthy controls (p = 0.006). Plasma level of LncRNA 17A, 51A and BC200 did not show a significant difference between two groups (p = 0.098, p = 0.204 and p = 0.232, respectively). ROC curve analysis showed that LncRNA BACE1 was the best candidate of these LncRNA (95% CI: 0.553–0.781, p = 0.003). In addition, no correlation was found for expression of these LncRNA in both control and AD groups with age or MMSE scale (p > 0.05). Conclusions Our present study compared the plasma level of four LncRNA between AD and non-AD patients, and found that the level of the BACE1 is increased in the plasma of AD patients and have a high specificity (88%) for AD, indicating BACE1 may be a potential candidate biomarker to predict AD. Electronic supplementary material The online version of this article (10.1186/s12883-017-1008-x) contains supplementary material, which is available to authorized users.

Dementia is an acquired progressive cognitive dysfunction, affecting the content of consciousness rather than the level of consciousness. Most dementia is senile dementia, accounting for the majority of dementia. The most important and common form of senile dementia is refractory dementia, which includes Alzheimer's disease (AD) and vascular dementia (VD). Due to the diversity and uncertainty of the pathogenic mechanism of VD and AD, no significantly effective drug currently exists. Berberine is a natural isoquinoline alkaloid extracted from Coptis chinensis that has a wide range of pharmacological effects. studies in recent years have also found that berberine can additionally treat senile dementia by affecting neurotransmitter, anti-oxidative stress, metabolism and other multi-target pathways. Multi-target treatment of senile dementia by berberine is a potential avenue of study for senile dementia treatment.

Isolated distal deep venous thrombosis (IDDVT) is a common complication after ischemic stroke. However, there is a paucity of evidence regarding the clinical features and risk factors of IDDVT in patients with acute ischemic stroke. This study aimed to establish and validate a clinical prediction scale of IDDVT at an early stage of ischemic stroke development.We retrospectively studied consecutive patients with stroke admitted to our neurology department between January and December 2016. Selected clinical variables were assessed by multivariable logistic regression to determine the independent risk factors for IDDVT. A prediction scale was developed and verified by the receiver operating characteristic curve.A total of 671 patients with ischemic stroke were included in the study, with 450 patients allocated into the derivation group and 221 patients into the validation group. A substantial proportion (22.1%) of patients developed IDDVT. A 16-point prediction scale (female gender = 2, older age [≥60 years] = 3, atrial fibrillation = 2, acute infection = 2, active cancer = 5, and higher [≥2.6 mmol/L] level of low-density lipoprotein = 2) derived from a multivariable logistic regression model was highly predictive of 10-day risk of IDDVT in both the validation group (c statistic = .70, 95% confidence interval [CI], .63-0.78, P .0001) and the derivation group (c statistic = .68, 95% CI, .63-0.74, P .0001).This prediction scale may help to identify patients with ischemic stroke who are at a higher risk of developing IDDVT.

This study investigates the neuroprotective properties of berberine (a natural isoquinoline alkaloid isolated from the Rhizoma coptidis) and finds that berberine could promote β-amyloid (Aβ) clearance and inhibit Aβ production in the triple-transgenic mouse model of Alzheimer's disease (3×Tg-AD). During the study, berberine was first administrated to treat 3×Tg-AD mice and primary neurons. Morris water maze assay, western blotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining and histological analysis, transmission electron microscopic analysis were then used to evaluate the effects of the berberine administration. The result showed that berberine significantly improved 3×Tg-AD mice's spatial learning capacity and memory retention, promoted autophagy activity identified by the enhancement of brain LC3-II, beclin-1, hVps34, and Cathepsin-D levels as well as the reduction of brain P62 and Bcl-2 levels in AD mice, facilitated reduction of Aβ and APP levels, reduced Aβ plaque deposition in the hippocampus of AD mice, and inhibited b-site APP cleavage enzyme 1 (BACE1) expression. Similar results were also found in 3×Tg-AD primary hippocampal neurons: berbernine treatment decreased the levels of extracellular and intracellular Aβ1-42, increased the protein levels of LC3-II, beclin-1, hVps34, and Cathepsin-D, and decreased the levels of P62, Bcl-2, APP and BACE1 levels. In summary, berberine shows neuroprotective effects on 3×Tg-AD mice and may be a promising multitarget drug in the preventionand protection against AD.

This study aims to investigate the inflammatory response characteristics of liver cells caused by HBV x protein (HBx) and the unique function of the PGE2 inhibitor on HBx-positive liver cells. Tetrazolium blue colorimetric method, flow cytometry, and Western blot were performed to detect the proliferation, cycle, and apoptosis protein expression of HBx-positive HL7702 liver and control cells. The effect of the PGE2 inhibitor 15-Deoxy-Δ(12,14)-prostaglandin J2 (15d-PGJ2) on the growth of HL7702-HBx was also observed. HBx induces the PGE2 accumulation in HL7702 liver cells and promotes their growth and inhibits their apoptosis. HL7702-HBx and HL7702 cells showed increased apoptosis rate, increased apoptosis-promoting protein expression, and reduced apoptosis-inhibiting protein expression under the effect of 15d-PGJ2, and the changes in HL7702-HBx cells were more significant than in HL7702 cells. HBx expression causes liver cells to be more sensitive to the apoptosis-promoting function of 15d-PGJ2. Therefore, the use of 15d-PGJ2 may be a new method for the prevention or treatment of inflammatory changes to cancer caused by HBV infection in liver cells.