Clinical features in antiglycine receptor antibody-related disease: a case report and update literature review.

Background and objectives: Antiglycine receptor (anti-GlyR) antibody mediates multiple immune-related diseases. This study aimed to summarize the clinical features to enhance our understanding of anti-GlyR antibody-related disease. Methods: By collecting clinical information from admitted patients positive for glycine receptor (GlyR) antibody, the clinical characteristics of a new patient positive for GlyR antibody were reported in this study. To obtain additional information regarding anti-GlyR antibody-linked illness, clinical data and findings on both newly reported instances in this study and previously published cases were merged and analyzed. Results: A new case of anti-GlyR antibody-related progressive encephalomyelitis with rigidity and myoclonus (PERM) was identified in this study. A 20-year-old man with only positive cerebrospinal fluid anti-GlyR antibody had a good prognosis with first-line immunotherapy. The literature review indicated that the common clinical manifestations of anti-GlyR antibody-related disease included PERM or stiff-person syndrome (SPS) (n = 179, 50.1%), epileptic seizure (n = 94, 26.3%), and other neurological disorders (n = 84, 24.5%). Other neurological issues included demyelination, inflammation, cerebellar ataxia and movement disorders, encephalitis, acute psychosis, cognitive impairment or dementia, celiac disease, Parkinson's disease, neuropathic pain and allodynia, steroid-responsive deafness, hemiballism/tics, laryngeal dystonia, and generalized weakness included respiratory muscles. The group of PERM/SPS exhibited a better response to immunotherapy than others. Conclusions: The findings suggest the presence of multiple clinical phenotypes in anti-GlyR antibody-related disease. Common clinical phenotypes include PERM, SPS, epileptic seizure, and paraneoplastic disease. Patients with RERM/SPS respond well to immunotherapy.

Evaluation of the causal effects of immune cells on ischemic stroke: a Mendelian randomization study.

Background: Ischemic stroke (IS) is a cerebrovascular disease caused by various factors, and its etiology remains inadequately understood. The role of immune system dysfunction in IS has been increasingly recognized. Our objective was to evaluate whether circulating immune cells causally impact IS risk. Methods: We conducted two-sample Mendelian randomization analyses to evaluate the causal effects of 731 immune cell traits on IS, utilizing publicly available genome-wide association studies (GWAS) summary statistics for 731 immune cell traits as exposure data, and two GWAS statistics for IS as outcome data. A set of sensitivity analyses, including Cochran's Q test, I 2 statistics, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out sensitivity analyses, were performed to assess the robustness of the results. Additionally, meta-analyses were conducted to combine the results from the two different IS datasets. Finally, we extracted instrumental variables of immune cell traits with causal effects on IS in both IS datasets for SNP annotation. Results: A total of 41 and 35 immune cell traits were identified to have significant causal effects on IS based on two different IS datasets, respectively. Among them, the immune cell trait CD62L- plasmacytoid Dendritic Cell AC and CD4+ CD8dim T cell%leukocyte respectively served as risk factor and protective element in both IS datasets. The robustness of the causal effects was confirmed through the sensitivity analyses. The results of the meta-analyses further support the causal effects of CD62L- plasmacytoid Dendritic Cell AC (pooled OR=1.030, 95%CI: 1.011-1.049, P=0.002) and CD4+ CD8dim T cell%leukocyte (pooled OR=0.959, 95%CI: 0.935-0.984, P=0.001). Based on these two immune cell traits, 33 genes that may be related to the causal effects were mapped. Conclusions: Our study demonstrated the potential causal effects of circulating immune cells on IS, providing valuable insights for future studies aimed at preventing IS.

Analysis and projections of disease burden for different risk factors and sexes of ischemic stroke in young adults in China.

To estimate the rate of death, and disability-adjusted life years (DALYs) and project the disease burden of ischemic stroke due to relevant risk factors in young adults age 20-49 years by sex in China. Data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 were used. The age-standardized mortality (ASMR), age-standardized DALYs rate (ASDR), and estimated annual percentage changes (EAPC) were calculated to evaluate the temporal trends from 1990 to 2019. We also used the NORDPRED model to predict ASMR for ischemic stroke due to related risk factors in Chinese young adults over the next 10 years. From 1990 to 2019, the general age-standardized mortality [from 2.39 (1.97 to 2.99) in 1990 to 1.8 (1.41 to 2.18) in 2019, EAPC = - 1.23] and DALYs rates (from 171.7 (140.34 to 212.36) in 1990 to 144.4 (114.29 to 177.37) in 2019, EAPC = - 0.86) decreased for ischemic stroke in young adults in China. ASMR and ASDR decreased for all level 1 risk factors (including behavioral, environmental/occupational, and metabolic) from 1990 to 2019, with the slightest decrease for metabolic risks [ASMR from 1.86 (1.39 to 2.41) in 1990 to 1.53 (1.15 to 1.92) in 2019, ASDR from 133.68 (99.96 to 173.89) in 1990 to 123.54 (92.96 to 156.98) in 2019] and the largest decrease for environmental/occupational risks [ASMR from 1.57 (1.26 to 1.98) in 1990 to 1.03 (0.78 to 1.29) in 2019, ASDR from 110.91 (88.44 to 138.34) in 1990 to 80.03 (61.87 to 100.33) in 2019]. In general, high body-mass index, high red meat intake, and ambient particulate matter pollution contributed to the large increase in ASMR and ASDR between 1990 and 2019. Significant reductions in ASMR and ASDR were observed in low vegetables intake, household air pollution from solid fuels, lead exposure, and low fiber intake. In addition, there were sex differences in the ranking of ASMR attributable to risks in ischemic stroke. The disease burden of ischemic stroke attributable to relevant risk factors in young adults in China is greater and has a faster growth trend or a slower decline trend in males than in females (except for secondhand smoke). The apparent increasing trend of ASMR attributable to high fasting plasma glucose, high systolic blood pressure, high body-mass index, and high red meat intake was observed in males but not in females. The projected analysis showed an increasing trend in ASMR between 1990 and 2030 for all specific metabolic risks for males, but a decreasing trend for females. ASMR attributable to ambient particulate matter pollution showed an increasing trend from 1990 to 2030 for both males and females. The burden of ischemic stroke in young adults in China showed a downward trend from 1990 to 2019. Specific risk factors associated with the burden of ischemic stroke varied between the sexes. Corresponding measures need to be developed in China to reduce the disease burden of ischemic stroke among young adults.

Association between stress hyperglycemia ratio and prognosis in acute ischemic stroke: a systematic review and meta-analysis.

BACKGROUND: Stress hyperglycemia is a relatively transient increase in blood glucose in response to inflammation of the body and neurohormonal disorders. It is still debated whether stress hyperglycemia ratio (SHR) in the acute phase, a new indicator of stress hyperglycemia, is related to poor prognosis in acute ischemic stroke (AIS) patients. This meta-analysis provides insight into the connection between SHR and prognosis in AIS patients. METHODS: We screened all potentially relevant studies using a comprehensive database search. The standardized mean difference (SMD) and 95% confidence interval (CI) were utilized to investigate the relationship between SHR in the acute phase and the prognosis of AIS. RESULTS: The pooled results revealed that AIS patients with poor prognoses had significantly higher SHR values than those with good prognoses (SMD = 0.56, 95%CI: 0.37-0.75, p<0.001). Subgroup analysis indicated that study design and differences in post-stroke treatment might be the sources of heterogeneity in this meta-analysis. CONCLUSIONS: High SHR in the acute period is related to poor prognosis after AIS. SHR may be a new predictor of poor outcomes in AIS patients.

CircPTK2 may be associated with depressive-like behaviors by influencing miR-182-5p.

BACKGROUND: Major depressive disorder (MDD) is a severe psychiatric disorder with uncertain causes. Recent studies have indicated correlations between circular RNAs (circRNAs) and psychiatric disorders. However, the potential role of circRNAs in MDD remains largely unknown. METHODS: We investigated the expression and diagnostic significance of circRNA protein tyrosine kinase 2 (circPTK2) by recruiting 50 MDD patients and 40 healthy subjects. Additionally, chronic unpredictable mild stress (CUMS) mouse model was established in animal experiments. QRT-PCR was adopted for circPTK2 and miR-182-5p levels. To investigate the role of circPTK2 in MDD, we utilized microinjection of circPTK2 adeno-associated virus into the mouse hippocampus. Depressive-like behaviors of mice were assessed through forced swim test and open field test. Additionally, the interaction between circPTK2 and miR-182-5p was validated using a dual luciferase reporter assay. RESULTS: Decreased expression of circPTK2 was found in peripheral blood mononuclear cells of MDD patients and in hippocampus of CUMS mice, which was useful for distinguishing MDD patients from healthy subjects. Notably, overexpression of circPTK2 was associated with depressive-like behaviors induced by CUMS. Further mechanism research demonstrated that circPTK2 functioned as the sponge for miR-182-5p, which may contribute to the beneficial effect of circPTK2. CONCLUSION: Collectively, our findings suggest the participation of circPTK2 and its underlying mechanism in MDD, which might provide a potential target for MDD therapy.

Effect and Mechanism of LIN28 on Ferroptosis in Mg2+-free Rat Hippocampal Neuron Model of Epilepsy.

Studies have demonstrated that LIN28 is expressed in the CNS and may exert protective effects on neurons. However, it remains unknown whether LIN28 regulates ferroptosis in the context of epilepsy. In this study, we established an epilepsy model by culturing hippocampal neurons from rats in a magnesium-free (Mg2+-free) medium. In Mg2+-depleted conditions, hippocampal neurons exhibited reduced LIN28 expression, heightened miR-142-5p expression, decreased glutathione peroxidase (GPX) activity and expression, elevated levels of reactive oxygen species (ROS) and malondialdehyde (MDA), resulting in a significant decline in cell viability and an increase in ferroptosis. Conversely, overexpression of LIN28 reversed these trends in the mentioned indices. Altogether, this study reveals that LIN28 may exert neuroprotective effects by inhibiting the miR-142-5p expression and suppressing ferroptosis in hippocampal neurons induced by Mg2+-free via increasing GPX4 expression.

Changing Patterns of Stroke and Subtypes Attributable to High Systolic Blood Pressure in China From 1990 to 2019.

BACKGROUND: It is unknown whether high systolic blood pressure had a similar effect on the disease burden of stroke subtypes. The aim of our study is to compare the long-term trends of stroke subtypes and sex groups attributable to high systolic blood pressure in China from 1990 to 2019. METHODS: Data about the age-standardized mortality rate and the age-standardized disability-adjusted life-year rate of stroke subtypes attributable to high systolic blood pressure in China were extracted in GBD (Global Burden of Disease) 2019. The trends in the age-standardized mortality rate and the age-standardized disability-adjusted life-year rate were calculated using the liner regression and age-period-cohort method, adjusted for age, period, and cohort. RESULTS: The estimated annual percentage change for mortality of stroke attributable to high systolic blood pressure was different from subtypes, with an estimated annual percentage change and 95% CI of 0.56 (0.37-0.74) for ischemic stroke (IS), -1.52 (-1.97 to -1.07) for intracerebral hemorrhage, and -7.02 (-7.86 to -6.17) for subarachnoid hemorrhage (SAH). The curve of the net drifts showed a downward trend for intracerebral hemorrhage and SAH, but that showed a stable trend for IS. The curve of local drifts showed a slow upward trend with age for IS, a slow downward trend for intracerebral hemorrhage, and a sharp downward trend for SAH. The drift curves showed different trends for males and females. The proportion of stroke mortality in young males was gradually increasing. The cohort rate ratio varied by subtypes, with the greatest decline for SAH, a slight decrease for intracerebral hemorrhage, and a slight increase for IS. The period rate ratio had decreased over the past 3 decades, with the greatest decline for SAH and the weakest decrease for IS. Moreover, both the period and cohort rate ratios for IS mortality due to high systolic blood pressure in males have increased significantly over the past 3 decades. CONCLUSIONS: Our results provided strong evidence that the disease burden of stroke attributable to high systolic blood pressure varied by subtypes and sex in China from 1990 to 2019. The age-standardized mortality rate and the age-standardized disability-adjusted life-year rate decreased for hemorrhagic stroke but increased for IS. Males had a higher mortality and exposure risk but a slighter decreasing trend than females. Our study suggested that greater attention should be given to the prevention of the burden of IS attributable to systolic blood pressure in China, especially for males.

Efavirenz restored NMDA receptor dysfunction and inhibited epileptic seizures in GluN2A/Grin2a mutant mice.

Introduction: N-methyl-D-aspartate receptor (NMDAR) is one of the main receptor of the excitatory neurotransmitter glutamate in the brain, which is the key determinant of the excitatory/inhibitory balance of neural network. GluN2A/GRIN2A is one of the subunits of NMDAR and plays an important role in epilepsy. Approximately 78% of patients with GluN2A/Grin2a mutations have epilepsy, and the underlying mechanism of this association is not well characterized. Methods: We constructed a mouse model of hyperthermic seizure, and conducted in vitro and in vivo electrophysiological and behavioral studies to clarify the pathogenic characteristics and mechanism of GluN2A/GRIN2A-V685G mutation. In addition, the drug efavirenz (EFV), which is used to treat HIV infection, was administrated to mutant animals to assess whether it can restore the loss of function. Results: Mutant mice showed no significant change in the mRNA or protein expressions of NMDAR compared with wild type (WT) mice. Mice with GluN2A/GRIN2A-V685G mutation exhibited shorter latency to seizure, increased frequency of seizure-like events, decreased peak current and current area of NMDAR excitatory postsynaptic current, and decreased event frequency of micro-inhibitory postsynaptic current, compared to WT mice. They also exhibited decreased threshold, increased amplitude, increased input resistance, and increased root number of action potential. EFV administration reversed these changes. The loss-of-function (LoF) mutation of NMDAR changed the excitatory/inhibitory balance of neural network, rendering animal more prone to seizures. Discussion: EFV was indicated to hold its potential in the treatment of inherited epilepsy.

Research landscape and trends of cerebral amyloid angiopathy: a 25-year scientometric analysis.

Background: Cerebral amyloid angiopathy (CAA), a cerebral small vessel disease affecting leptomeningeal and cortical small blood vessels, is a common cause of spontaneous lobar intracerebral hemorrhage and cognitive impairment, particularly in elderly patients. This study aims to investigate the field of CAA research from a scientometric perspective. Methods: Publications related to CAA from January 1st, 1999 to September 29th, 2023 were retrieved from the Web of Science Core Collection database. The scientometric software VOSviewer and CiteSpace were used to analyze and visualize the publication trends, countries/regions, institutions, authors, journals, cited references, and keywords of CAA. Results: A total of 2,798 publications related to CAA from 73 countries/regions, led by the United States, were included. The number of publications showed an increasing trend over time. Massachusetts General Hospital was the most productive institution, and authors Greenberg and Charidimou published the most papers and were most frequently co-cited. Journal of Alzheimer's Disease was the most prolific journal in this field, and Neurology was the most co-cited journal. Apart from "cerebral amyloid angiopathy", the most frequently used keywords were "Alzheimer's disease", "amyloid beta", "intracerebral hemorrhage", and "dementia". The burst keywords in recent years included "cortical superficial siderosis" and "dysfunction". Conclusions: This scientometric analysis provides a comprehensive overview of CAA research over the past 25 years, and offers important insights for future research directions and scientific decision-making in this field.

Comparative efficacy and acceptability of selective serotonin reuptake inhibitor antidepressants for binge eating disorder: A network meta-analysis.

Background: There are several selective serotonin reuptake inhibitor (SSRI) antidepressants currently used to treat binge eating disorder (BED), but the efficacy and acceptability of these antidepressants are still controversial. Therefore, we designed a network meta-analysis (NMA) to compare the efficacy and acceptability of different SSRI antidepressants for the treatment of BED. Methods: Four databases including PubMed, Embase, the Cochrane Library, and Web of Science were systematically searched for the eligible randomized controlled trials (RCTs) for the treatment of patients with BED. The analysis was performed with Stata16 software. Results: 9 RCTs were included in this NMA. The results of the study showed that compared with placebo, sertraline and fluoxetine could significantly reduce the frequency of binge eating. Fluoxetine was shown to be the drug with the greatest reduction in Hamilton Rating Scale for Depression (HAMD) score. Besides, all SSRI antidepressants were ineffective in losing weight. In addition, all the investigated antidepressants were found to be well acceptable in regards to the acceptability reflected by the dropout rate. Conclusion: As far as both efficacy and acceptability were concerned, fluoxetine might be the best choice.

Higher levels of peripheral blood glucose in the acute stage of stroke increase the risk of post-stroke depression: A systematic review and meta-analysis.

BACKGROUND: Multiple investigations have shown that diabetes mellitus is a predictor of post-stroke depression (PSD). However, whether elevated levels of fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) are associated with an increased risk of PSD remains controversial. METHODS: We comprehensively searched databases for eligible studies. Standard mean differences and 95% confidence intervals were used to examine the relationship between peripheral blood glucose levels during the acute phase of stroke and the risk of PSD. Narrative syntheses and meta-analyses were conducted when appropriate unadjusted or adjusted ORs were available. RESULTS: A total of 21 prospective cohort studies were included in the analysis. PSD patients had significantly higher peripheral blood glucose levels than non-PSD patients (FPG: SMD, 0.28, 95% CI, 0.11-0.45, p＜0.01, HbA1c: SMD, 0.49, 95%CI, 0.20-0.78, p＜0.01, respectively). In the subgroup analyses by classifying the time point of depression assessment, HbA1c was more statistically significant associated with the risk of PSD than FPG. Differences in the prevalence of diabetes were not heterogeneity sources. CONCLUSION: Higher levels of peripheral blood glucose in the acute phase of stroke increase the risk of PSD. HbA1c might be a better biomarker for the risk of PSD than FPG.

Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Monocyte-to-Lymphocyte Ratio in Depression: An Updated Systematic Review and Meta-Analysis.

Background: Research on neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) in depression is still emerging and has increased 3-fold since the first meta-analysis. An updated meta-analysis with sufficient studies can provide more evidence for a potential relationship between NLR, PLR, MLR, and depression. Methods: We identified 18 studies from the PubMed, EMBASE, Cochrane library, and Web of Science databases. Meta-analyses were performed to generate pooled standardized mean differences (SMDs) and 95% confidence intervals (CIs) between patients with depression and controls. Sensitivity analysis, subgroup analysis, meta-regression, and publication bias were conducted. Results: A total of 18 studies including 2,264 depressed patients and 2,415 controls were included. Depressed patients had significantly higher NLR and PLR compared with controls (SMD = 0.33, 95% CI: 0.15-0.52, p < 0.001 and SMD = 0.24, 95% CI: 0.02-0.46, p < 0.05, respectively). MLR was slightly higher in depressed individuals compared to controls (SMD = 0.15, 95% CI: -0.26 to 0.55, p > 0.05), despite the absence of significance. Sensitivity analysis removing one study responsible for heterogeneity showed a higher and significant effect (SMD = 0.32, 95% CI: 0.20-0.44) of MLR. Three subgroup analyses of NLR, PLR, MLR, and depression revealed obvious differences in the inflammatory ratios between depressed patients and controls in China and the matched age and gender subgroup. Individuals with post-stroke depression (PSD) had higher NLR and MLR values as compared to non-PSD patients (SMD = 0.51, 95% CI: 0.36-0.67, p < 0.001 and SMD = 0.46, 95% CI: 0.12-0.79, p < 0.01, respectively). Meta-regression analyses showed that male proportion in the case group influenced the heterogeneity among studies that measured NLR values (p < 0.05). Conclusions: Higher inflammatory ratios, especially NLR, were significantly associated with an increased risk of depression. In the subgroup of China and matched age and gender, NLR, PLR, and MLR were all elevated in depressed patients vs. controls. Individuals with PSD had higher NLR and MLR values as compared to non-PSD patients. Gender differences may have an effect on NLR values in patients with depression.

Risk Factors for Mechanical Ventilation in Patients with Guillain-Barré Syndrome.

BACKGROUND: Respiratory support is required in 20-30% of patients with Guillain-Barré syndrome (GBS). We investigated clinical and biological risk factors for mechanical ventilation (MV) in northeast China through a retrospective GBS study. The Erasmus GBS Respiratory Insufficiency Score (EGRIS) is a prognostic model for MV in patients with GBS, and its usefulness has been validated in several countries but not in China. Therefore, we intended to validate the EGRIS model in our GBS cohort. METHODS: A total of 252 patients with GBS were included in this study from January 2013 to October 2017. Risk factors for MV were identified via multivariate logistic regression analysis. The prognostic value of the EGRIS was validated via receiver operating characteristic curve analysis. RESULTS: Thirty-one patients (12.3%) required MV (mean age 54.19 years), with a majority being male (77.4%). The risk factors for MV were male sex [odds ratio (OR) 3.720, 95% confidence interval (CI) 1.155-11.985, p < 0.05], shorter interval from onset to admission (OR 0.830, 95% CI 0.711-0.970, p < 0.05), lower Medical Research Council sum score at admission (OR 0.942, 95% CI 0.911-0.973, p < 0.001), neutrophil-to-lymphocyte ratio at admission (OR 1.174, 95% CI 1.049-1.315, p < 0.01), and cranial nerve deficit (OR 3.805, 95% CI 1.373-10.541, p < 0.05). The EGRIS had a good predictive ability for MV (area under the receiver operating curve 0.861) in patients with GBS, and a high EGRIS was a predictor for MV (OR 8.778, 95% CI 3.432-22.448, p < 0.001). However, there was no significant difference in ganglioside administration between ventilated and nonventilated patients. CONCLUSIONS: An elevated neutrophil-to-lymphocyte ratio at admission and a high EGRIS could serve as predictors for MV in our GBS cohort.

Higher levels of C-reactive protein in the acute phase of stroke indicate an increased risk for post-stroke depression: A systematic review and meta-analysis.

BACKGROUND: Investigations have revealed the association between inflammation and post-stroke depression (PSD). However, whether the C-reactive protein (CRP) level, a biomarker of inflammation, would affect the development of PSD is still controversial. METHODS: A systematic search of databases was performed for eligible studies. Standardized Mean Difference (SMD) with 95 % Confidence Interval (CI) was used to assess the association between the CRP level in the acute phase of stroke and the risk of PSD. RESULTS: 13 cohort studies that involved 3536 participants were included. Combined results showed that compared with non-PSD patients, the CRP level of PSD patients was significantly higher on admission (SMD = 0.19, 95 % CI: 0.12-0.27). A subgroup analysis by classifying the assessment time of depression showed obvious differences of the CRP levels between the PSD patients who were diagnosed more than 1 month after stroke and the non-PSD (1-3 months: SMD = 0.16, 95 % CI: 0.06-0.25; >3months: SMD = 0.34, 95 % CI: 0.18-0.51). CONCLUSION: A higher level of CRP in the acute phase of stroke suggests an increased risk for PSD.

RNF34 ablation promotes cerebrovascular remodeling and hypertension by increasing NADPH-derived ROS generation.

Cerebrovascular remodeling is the most common cause of hypertension and stroke. Ubiquitin E3 ligase RING finger protein 34 (RNF34) is suggested to be associated with the development of multiple neurological diseases. However, the importance of RNF34 in cerebrovascular remodeling and hypertension is poorly understood. Herein, we used mice with a global RNF34 knockout as well as RNF34 floxed mice to delete RNF34 in endothelial cells and smooth muscle cells (SMCs). Our results showed that global RNF34 knockout mice substantially promoted angiotensin II (AngII)-induced middle cerebral artery (MCA) remodeling, hypertension, and neurological dysfunction. Endothelial cell RNF34 did not regulate the development of hypertension. Rather, SMC RNF34 expression is a critical regulator of hypertension and MCA remodeling. Loss of RNF34 enhanced AngII-induced mouse brain vascular SMCs (MBVSMCs) proliferation, migration and invasion. Furthermore, MCA and MBVSMCs from SMC RNF34-deficient mice showed increased superoxide anion and reactive oxygen species (ROS) generation as well as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, but exhibited no marked effect on mitochondria-derived ROS. Knockout of RNF34 promoted p22phox expression, leading to increased binding of p22phox/p47phox and p22phox/NOX2, and eventually NADPH oxidase complex formation. Immunoprecipitation assay identified that RNF34 interacted with p22phox. RNF34 deletion increased p22phox protein stability by inhibiting ubiquitin-mediated degradation. Blockade of NADPH oxidase activity or knockdown of p22phox significantly abolished the effects of RNF34 deletion on cerebrovascular remodeling and hypertension. Collectively, our study demonstrates that SMC RNF34 deficiency promotes cerebrovascular SMC hyperplasia and remodeling by increased NADPH-derived ROS generation via reducing p22phox ubiquitin-dependent degradation.

A Case With IgG4-Related Spinal Pachymeningitis Causing Spinal Cord Compression.

Immunoglobulin G4 (IgG4)-related disease is a systemic disease characterized by sclerosing lesions and an increased serum IgG4 level. This condition can involve any organ, but IgG4-related spinal pachymeningitis is relatively rare. In the current study, we report a case of spinal cord compression caused by IgG4-related spinal pachymeningitis. A 39-year-old man presented to us with a 15-day history of back pain and a 3-day history of dysuresia, exacerbated by weakness in the lower extremities for 2 days. Cervical magnetic resonance imaging (MRI) showed strip-shaped abnormal signals along the anterior and posterior borders of the spinal cord at the C5-T4 levels. The IgG level in cerebrospinal fluid was 718.0 mg/L. Thoracic MRI revealed strip-shaped abnormal signals with remarkable enhancement along the anterior and posterior borders of the dural sac at the T1-T6 levels. Histopathological examination confirmed IgG4-related spinal pachymeningitis. The symptoms worsened rapidly, and surgical resection of the space-occupying lesion in the vertebral canal was performed for spinal decompression. Corticosteroid therapy was administered, and the patient's motor functions were mildly improved. IgG4-related disease can manifest as spinal pachymeningitis and cause spinal cord compression. Clinicians should be aware of this rare condition, and early diagnosis, timely surgical decompression, and appropriate corticosteroid therapy should be highlighted.

ClC-3 induction protects against cerebral ischemia/reperfusion injury through promoting Beclin1/Vps34-mediated autophagy.

Acute ischemic stroke is a devastating disease with very limited therapeutics. Growing appreciation of dysregulated autophagy contributes to the progression of brain ischemic injury, making it to be an appealing intervention target. In terms of its well-characterized consequences, the signal molecules required for autophagy activation are rather poorly defined. Here, we found the induction of chloride channel-3 (ClC-3) directly activated autophagy, which played an important role in limiting cerebral ischemia/reperfusion (I/R) injury. Further mechanism exploration discovered that the up-regulation of ClC-3 was critical for the interaction of Beclin1 and Vps34. After ClC-3 knockdown using adeno-associated virus vectors in vivo, the autophagy activation was partially inhibited through disrupting the formation of Beclin1 and Vps34 complex. Consistent with these observations, ClC-3 knockdown could also significantly aggravated cerebral I/R injury through suppressing autophagy in vivo, which further confirmed the neuroprotective roles of ClC-3. Collectively, we provided an novel evidence for ClC-3 serving as a crucial regulator of autophagy; and our results indicated that the induction of ClC-3 may serve as a self-protective mechanism against cerebral I/R injury.

Short-Term Efficacy and Tolerability of Paroxetine Versus Placebo for Panic Disorder: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To explore the short-term efficacy and tolerability of paroxetine in the treatment of panic disorder in adults. METHODS: Multiple electronic databases were searched to find randomized controlled trials (RCTs) on paroxetine and panic disorder. The primary efficacy outcomes were: the mean change compared to the baseline in the total number of full panic attacks, Clinical Global Impression-Severity of Illness (CGI-S) score, and the proportion of participants with zero full panic attacks and with a 50% or greater reduction in the number of full panic attacks. The tolerability outcomes included withdrawal rate and the incidence of adverse events (AEs). RESULTS: 13RCTs were included. The pooled analyses showed patients who received paroxetine experienced greater improvements in the number of full panic attacks (total: MD=-1.96, 95%CI -3.45 to -0.47, P=0.010; ≥50% reduction: OR=1.66, 95%CI 1.08 to 2.55, P=0.02; zero full panic attacks: OR=1.70, 95%CI 1.42 to 2.03, P < 0.00001) and CGI-S (MD=-0.37, 95%CI -0.74 to -0.01, P=0.05) than placebo. There was no evident difference in the total withdrawal rate (OR=0.91, 95%CI 0.76 to 1.08, P=0.26) and withdrawal rate due to AEs (OR=1.29, 95%CI 0.97 to 1.72, P=0.07) between the two groups. Withdrawal rate due to lack of efficacy or relapse (OR=0.44, 95%CI 0.31 to 0.63, P < 0.00001) and the incidence of serious AEs (OR=0.42, 95%CI 0.23 to 0.79, P=0.007) in the paroxetine group was lower than the placebo group. Meanwhile, the incidence of any treatment-emergent adverse events (TEAEs) (OR=1.32, 95%CI 1.05 to 1.64, P=0.02) in the paroxetine group was higher in comparison with the placebo. CONCLUSIONS: Paroxetine is an effective and well-tolerated short-term treatment for adults with panic disorder.

Efficacy and tolerability of paroxetine in adults with social anxiety disorder: A meta-analysis of randomized controlled trials.

OBJECTIVE: The present study aimed to estimate the comprehensive efficacy and tolerability of paroxetine in adult patients with social anxiety disorder (SAD). METHODS: We conducted a comprehensive literature review of the PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials databases for eligible randomized controlled trials (RCTs). The efficacy outcome was the mean change of different kinds of scale scores as well as response and remission rates. The secondary outcome was tolerability, defined as the discontinuation rate and the incidence of adverse events (AEs). RESULTS: Our meta-analysis included 13 RCTs. Mean changes in the Liebowitz Social Anxiety Scale (LSAS) total score, fear and avoidance subscale of LSAS scores were all significantly greater in patients with SAD that received paroxetine compared to those received placebo (total: MD = 13.46, 95%CI 10.59-16.32, P < .00001; fear: MD = 6.76, 95%CI 4.89-8.62, P < .00001; avoidance: MD = 6.54, 95%CI 4.63-8.45, P < .00001). Response and remission rates were both significantly greater in patients with SAD that received paroxetine compared to those received placebo (response: OR = 3.02, 95%CI 2.30-3.97, P < .00001; remission: OR = 3.14, 95%CI 2.25-4.39, P < .00001). There was no significant difference in discontinuation rate due to any reason between two groups (OR = 1.06, 95%CI 0.81-1.39, P = .65). Discontinuation rate due to AEs was higher in paroxetine than placebo group (OR = 3.41, 95%CI 2.45-4.72, P < .00001) whereas the rate due to lack of efficacy was higher in placebo as compared with paroxetine group (OR = 0.14, 95%CI 0.09-0.22, P < .00001). The incidence of any AE was significantly increased in patients that received paroxetine (OR = 1.83, 95%CI 1.43-2.35, P < .00001). CONCLUSION: Paroxetine was an effective and well-tolerated treatment option for adult patients with SAD.

Ligustrazine prevents basilar artery remodeling in two-kidney-two-clip renovascular hypertension rats via suppressing PI3K/Akt signaling.

OBJECTIVE: In the present study, we used a two-kidney-two-clip (2k2c) stroke-prone renovascular hypertension rat model (RHRSP) to investigate the protective effects of ligustrazine (TMP) on cerebral arteries and to examine PI3K/Akt pathway behavior under this protection. METHODS: The cerebral artery remodeling was induced by 2k2c-induced renovascular hypertension. Brain basilar artery tissues were isolated and their histological changes were detected through H&E and EVG staining, α-SMA IHC staining, and transmission electron microscopy at four, eight, and twelve weeks after 2k2c surgery, both with and without TMP treatment. Meanwhile, the ET-1, Ang II, and NO levels in basilar arteries and plasma were determined. Furthermore, the PTEN expression and the activation of PI3K/Akt in basilar artery tissues were detected through IHC and Western Blot. In addition, the primary basilar artery smooth muscle cells (BASMCs) were cultured and TMP protection of BASMCs stimulated with ET-1/Ang II in the presence or absence of insulin-like growth factor 1 (IGF-1) was determined. RESULTS: TMP attenuated basilar artery remodeling, decreased ET-1 and Ang II levels and increased NO level in basilar arteries and plasma of RHRSP rats. Moreover, TMP reduced BASMCs proliferation upon ET-1/Ang II stimulation. We also found that TMP could effectively suppress the activation of PI3K/Akt in 2k2c-RHRSP rat basilar artery and ET-1/Ang II stimulated BASMCs. Most importantly, IGF-1, as an activator of PI3K/Akt, could damage the protective effect of TMP. CONCLUSIONS: TMP exerts its protective effects and prevents basilar artery remodeling in RHRSP rats at least partly through the inhibition of PI3K/Akt pathway.