Intravenous Alteplase Versus Best Medical Therapy for Patients With Minor Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: The efficacy of thrombolysis (IVT) in minor stroke (National Institutes of Health Stroke Scale score, 0-5) remains inconclusive. The aim of this study is to compare the effectiveness and safety of IVT with best medical therapy (BMT) by means of a systematic review and meta-analysis of randomized controlled trials and observational studies. METHODS: We searched the PubMed, Embase, Cochrane Library, and Web of Science databases to obtain articles related to IVT in minor stroke from inception until August 10, 2023. The primary outcome was an excellent functional outcome, defined as a modified Rankin Scale score of 0 or 1 at 90 days. The associations were calculated for the overall and preformulated subgroups by using the odds ratios (ORs). This study was registered with PROSPERO (CRD42023445856). RESULTS: A total of 20 high-quality studies, comprised of 13 397 patients with acute minor ischemic stroke, were included. There were no significant differences observed in the modified Rankin Scale scores of 0 to 1 (OR, 1.10 [95% CI, 0.89-1.37]) and 0 to 2 (OR, 1.16 [95% CI, 0.95-1.43]), mortality rates (OR, 0.67 [95% CI, 0.39-1.15]), recurrent stroke (OR, 0.89 [95% CI, 0.57-1.38]), and recurrent ischemic stroke (OR, 1.09 [95% CI, 0.68-1.73]) between the IVT and BMT group. There were differences between the IVT group and the BMT group in terms of early neurological deterioration (OR, 1.81 [95% CI, 1.17-2.80]), symptomatic intracranial hemorrhage (OR, 7.48 [95% CI, 3.55-15.76]), and hemorrhagic transformation (OR, 4.73 [95% CI, 2.40-9.34]). Comparison of modified Rankin Scale score of 0 to 1 remained unchanged in subgroup patients with nondisabling deficits or compared with those using antiplatelets. CONCLUSIONS: These findings indicate that IVT does not yield significant improvement in the functional prognosis of patients with acute minor ischemic stroke. Additionally, it is associated with an increased risk of symptomatic intracranial hemorrhage when compared with the BMT. Moreover, IVT may not have superiority over BMT in patients with nondisabling deficits or those using antiplatelets.

Poly (ADP-Ribose) polymerase 1 and parthanatos in neurological diseases: From pathogenesis to therapeutic opportunities.

Poly (ADP-ribose) polymerase-1 (PARP-1) is the most extensively studied member of the PARP superfamily, with its primary function being the facilitation of DNA damage repair processes. Parthanatos is a type of regulated cell death cascade initiated by PARP-1 hyperactivation, which involves multiple subroutines, including the accumulation of ADP-ribose polymers (PAR), binding of PAR and apoptosis-inducing factor (AIF), release of AIF from the mitochondria, the translocation of the AIF/macrophage migration inhibitory factor (MIF) complex, and massive MIF-mediated DNA fragmentation. Over the past few decades, the role of PARP-1 in central nervous system health and disease has received increasing attention. In this review, we discuss the biological functions of PARP-1 in neural cell proliferation and differentiation, memory formation, brain ageing, and epigenetic regulation. We then elaborate on the involvement of PARP-1 and PARP-1-dependant parthanatos in various neuropathological processes, such as oxidative stress, neuroinflammation, mitochondrial dysfunction, excitotoxicity, autophagy damage, and endoplasmic reticulum (ER) stress. Additional highlight contains PARP-1's implications in the initiation, progression, and therapeutic opportunities for different neurological illnesses, including neurodegenerative diseases, stroke, autism spectrum disorder (ASD), multiple sclerosis (MS), epilepsy, and neuropathic pain (NP). Finally, emerging insights into the repurposing of PARP inhibitors for the management of neurological diseases are provided. This review aims to summarize the exciting advancements in the critical role of PARP-1 in neurological disorders, which may open new avenues for therapeutic options targeting PARP-1 or parthanatos.

Crosstalk between peripheral and the brain-resident immune components in epilepsy.

Epilepsy is one of the most common neurology diseases. It is characterized by recurrent, spontaneous seizures and accompanied by various comorbidities which can significantly affect a person's life. Accumulating evidence indicates an essential pathophysiological role for neuroinflammation in epilepsy, which involves activation of microglia and astrocytes, recruitment of peripheral leukocytes into the central nervous system, and release of some inflammatory mediators, including pro-inflammatory factors and anti-inflammatory cytokines. There is complex crosstalk between the central nervous system and peripheral immune responses associated with the progression of epilepsy. This review provides an update of current knowledge about the contribution of this crosstalk associated with epilepsy. Additionally, how gut microbiota is involved in epilepsy and its possible influence on crosstalk is also discussed. Such recent advances in understanding suggest innovative methods for targeting the molecules correlated with the crosstalk and may provide a better prognosis for patients diagnosed with epilepsy.

Ketogenic diet prevents paclitaxel-induced neuropathic nociception through activation of PPARγ signalling pathway and inhibition of neuroinflammation in rat dorsal root ganglion.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect during the course of cancer treatment, which is mainly manifested as a series of sensory abnormalities. At present, there are no recommended prevention or treatment strategies, and the underlying mechanisms are unclear. The ketogenic diet (KD), a special diet that is high in fat and low in carbohydrate intake, shows good therapeutic potential in children with epilepsy. In this study, it was found that KD significantly prevented paclitaxel-induced neuropathic nociception. Using the GSE113941 database, 281 differentially expressed genes (DEGs) were found in an animal model of CIPN and controls. The DEGs were mainly enriched in peroxisome proliferator activated receptor (PPAR) and oxidative phosphorylation signalling pathways. As a main regulatory pathway of lipid metabolism, the PPARγ signalling pathway was significantly upregulated in the KD model. In addition, KD also inhibited the expression of pro-inflammatory cytokines and the TLR4/NF-κB signalling pathway in the dorsal root ganglion (DRG) in paclitaxel-treated rats. In vitro, rat primary DRG neurons were used to investigate the role of PPARγ in paclitaxel-induced neurotoxicity. It was found that PPARγ agonist rosiglitazone significantly protected DRG neurons against cell apoptosis and reactive oxygen species generation induced by paclitaxel administration. Therefore, KD is a prospective treatment option when applied as a dietary intervention in the prevention and treatment of paclitaxel-induced neuropathic nociception, possibly through the activation of PPARγ and its neuroprotective functions.

Neuroprotective effects of miR-532-5p against ischemic stroke.

Stroke can cause death and disability and has a high incidence with many complications. So far, effective treatment options for stroke are still limited. MicroRNA-532-5p (miR-532-5p) is significantly downregulated in stroke. However, the role of miR-532-5p in ischemic stroke is still unclear. In this study, we established an in vivo middle cerebral artery occlusion (MCAO) model in mice. The expression level of miR-532-5p, neurological score, infarct area, neuronal apoptosis, and phosphoinositide 3-kinase (PI3K)/Akt signaling pathway-related molecules were examined. Low miR-532-5p levels and high phosphatase and tensin homolog deleted on chromosome 10 (PTEN) levels were detected in the mouse MCAO model. MiR-532-5p overexpression improved neurological dysfunction, reduced the infarct area, attenuated neuronal injury and apoptosis, and promoted the activation of the PI3K/Akt signaling pathway in MCAO mice. In vitro, we treated mouse neuroblastoma cells (N2a) with oxygen-glucose deprivation and reperfusion (OGD/R). The expression level of miR-532-5p, cell viability, cell apoptosis, and the PI3K/Akt signaling pathway-related molecules were detected. Consistent with the in vivo tests, the miR-532-5p level was decreased and the PTEN level was increased in OGD-treated N2a cells in vitro. The miR-532-5p mimic increased cell viability, decreased cell apoptosis, and activated the PI3K/Akt signaling pathway. Furthermore, PTEN was verified as a target gene of miR-532-5p by luciferase reporter assay. PTEN overexpression attenuated the protective effect of miR-532-5p in OGD-treated N2a cells. In summary, these findings reveal that miR-532-5p protects against ischemic stroke by inhibiting PTEN and activating the PI3K/Akt signaling pathway and may serve as a novel therapeutic target for ischemic stroke.

Targeting strategies for chemotherapy-induced peripheral neuropathy: does gut microbiota play a role?

Chemotherapy-induced peripheral neuropathy (CIPN) is a progressive, often irreversible condition that produces severe neurological deficits. Emerging data suggest that chemotherapy also exerts detrimental effects on gut microbiota composition and intestinal permeability, contributing to dysbiosis and inflammation. Compared with other complications associated with chemotherapy, such as diarrhoea and mucositis, CIPN is of particular concern because it is the most common reason for terminating or suspending treatment. However, specific and effective curative treatment strategies are lacking. In this review, we provide an update on current preclinical and clinical understandings about the role of gut microbiota in CIPN. The gut microbiota serves as an intersection between the microbiome-gut-brain and the neuroimmune-endocrine axis, forming a complex network that can directly or indirectly affect key components involved in the manifestations of CIPN. Herein, we discuss several potential mechanisms within the context of the networks and summarize alterations in gut microbiome induced by chemotherapeutic drugs, providing great potential for researchers to target pathways associated with the gut microbiome and overcome CIPN.

Association of apolipoprotein E genotypes with epilepsy risk: A systematic review and meta-analysis.

OBJECTIVE: The objective of this study was to identify the association between certain genotypes or alleles of the APOE (Apolipoprotein E) gene and the epilepsy risk. METHODS: All studies on human APOE genotypes associated with epilepsy were included. Separate meta-analyses were conducted between the patients with epilepsy and the control group from the following three aspects: ε4 carriers or ε2 carriers vs ε3/ε3 (the ε2/ε4 genotype was excluded), ε4 carriers vs ε2 carriers, and five genotypes vs ε3/ε3. The subgroup analysis was conducted on the ethnicity, the control group was healthy or not, and type of epilepsy. RESULTS: Nine studies with 2210 individuals were included. Compared with ε3/ε3 genotype, ε4 carriers increased the epilepsy risk (odds ratios [ORs]: 1.27; 95% confidence intervals [CI]: 1.01 to 1.59; P = 0.042), while ε2 carriers had no association with epilepsy risk (OR: 0.88; 95% CI: 0.66 to 1.18; P = 0.184). The risk of epilepsy was 1.45 times greater in ε4 carriers compared with ε2 carriers (OR: 1.45; 95% CI: 1.02 to 2.04; P = 0.037). When the number of APOE ε4 allele increased, the ORs increased progressively (no ε4 alleles, OR: 0.88, 95% CI: 0.66 to 1.18; one ε4 allele, OR: 1.25, 95% CI: 0.99 to 1.57; two ε4 alleles, OR: 1.84, 95% CI: 0.83 to 4.10). Apolipoprotein E ε4 carriers had a higher epilepsy risk in the population without primary diseases (OR: 1.43; 95% CI: 1.09 to 1.88), and a higher risk in Asian populations (OR: 1.67; 95% CI: 1.12 to 2.49). CONCLUSIONS: Apolipoprotein E ε4 allele genotype was associated with an increased epilepsy risk, which was more prominent in the Asian and the population without primary diseases. These findings may be used to guide the directions of prevention and treatment on epilepsy. Larger clinical studies are needed.

Effects of valproate on reproductive endocrine function in male patients with epilepsy: A systematic review and meta-analysis.

BACKGROUND: Valproate (VPA) is a broad spectrum antiepileptic drug (AED) that is generally used as a first line agent for most idiopathic and symptomatic generalized epilepsies. Many studies have indicated that AEDs cause reproductive endocrine disorders in males, but the exact etiology underpinning these dysfunctions is not clear. This meta-analysis and systematic review was intended to evaluate the effect of VPA on reproductive endocrine function in male patients with epilepsy. METHODS: A literature search was performed using electronic databases up to December 2017 for eligible studies. The differences in the levels of the reproductive factors, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone binding globulin (SHBG), testosterone, dehydroepiandrosterone sulfate (DHEAS), and androstenedione (ADION) in the male patients with epilepsy treated with VPA (treatment group) were compared with the those of the healthy controls (control group) by the use of the Standardized mean difference (SMD) with 95% confidence intervals (CIs). RESULTS: Six publications with a total of 316 subjects were identified. The result revealed that the levels of FSH (SMD = -1.33, 95% CI: -2.60 to -0.07, P = 0.039) and testosterone (SMD = -0.45, 95% CI: -0.87 to -0.03, P = 0.038) of the treatment group were decreased significantly compared with the healthy controls. There was an increase in the levels of SHBG (SMD = 0.41, 95% CI: -0.21 to 1.03, P = 0.197), DHEAS (SMD = 0.20, 95% CI: -0.06 to 0.45, P = 0.126) and ADION (SMD = 0.73, 95% CI: -0.10 to 1.57, P = 0.086), and a decrease in that of LH(SMD = -0.71, 95% CI: -1.49 to 0.07, P = 0.075) in the male patients with epilepsy treated with VPA, but the differences did not reach statistical significance (P > 0.05). CONCLUSIONS: This meta-analysis indicates that VPA may lead to a significant decrease in the levels of FSH and testosterone and alter the concentrations of LH, DHEAS, SHBG, and ADION to some extent, which might contribute to the reproductive endocrine dysfunction in male patients with epilepsy. It is important for clinical neurologists to be cautious when prescribing VPA to reproductive-aged male patients with epilepsy.

Aberrant plasticity in the hippocampus after neonatal seizures.

Purpose/aim of the study: Neonatal seizures are the most frequent type of neurological disorder, and those newborn babies that experience seizures carry an increased risk of epileptogenesis and other long-term morbidities. The aims of this review were to summarize the different effects on hippocampal neurogenesis between neonatal seizures and adult seizures. MATERIALS AND METHODS: Pubmed, Medline and Cochrane Library were searched for articles that examined the aberrant plasticity in the hippocampus after neonatal seizures. RESULTS: Different from the adult animals, the proliferation of newly formed dentate granule cells is reduced in the acute phase and enhanced in the chronic phase after neonatal seizures. Neonatal seizures cause less ectopic migration of newborn neurons. Recurrent neonatal seizures also switch the effect of gamma-aminobutyric acid receptor activation from inhibition to excitation, which may contribute to increased seizure susceptibility. Similar to adult seizures, mossy fiber sprouting and sprouting of basal dendrites had been seen after neonatal seizures. CONCLUSIONS: The effects of seizures on neurogenesis in the hippocampus are age-dependent.

Safety and Efficacy of Thrombolysis in Cervical Artery Dissection-Related Ischemic Stroke: A Meta-Analysis of Observational Studies.

BACKGROUND: Although thrombolysis is considered to be the first-line treatment for ischemic stroke, there remains an ongoing controversy on the safety and efficacy of thrombolysis in cervical artery dissection (CAD). The aim of this meta-analysis was to assess observational data related to the safety and efficacy of thrombolysis in CAD-related ischemic stroke. METHODS: We performed a systematic search of the efficacy of thrombolysis treatment in CAD-related ischemic stroke with appropriate observational studies identified for the study. The meta-analysis models in Comprehensive Meta-Analysis V2 software were applied to calculate the merged rates of favorable outcome (modified Rankin Scale, mRS 0-2), excellent outcome (mRS 0-1), intracranial hemorrhage (ICH), symptomatic ICH (SICH), mortality and recurrent stroke between thrombolysis and non-thrombolysis in CAD-related stroke. The difference of outcomes and adverse events between the 2 groups was compared by analyzing the pooled OR value and chi-square test using the software SPSS. RESULTS: A total of 846 patients were identified from 10 studies (174 with thrombolysis; 672 with non-thrombolysis). The meta-analysis detected no significant statistical difference in the proportion of CAD-related stroke patients enjoying a favorable outcome at the 3 months' follow-up between the thrombolysis and non-thrombolysis groups (53.7 vs. 58.2%, OR 0.782, x03C7;2 = 0.594, p > 0.05); non-thrombolysis was slightly superior than thrombolysis in terms of excellent outcome (52.4 vs. 34.4%, OR 0.489, x03C7;2 = 9.143, p = 0.002). There was no significant difference in SICH, mortality and recurrent stroke rates between the 2 groups (all p > 0.05). ICH rate was higher in the thrombolysis group of CAD-related stroke patients compared to that in the non-thrombolysis group (12.3 vs. 7.4%, OR 2.647, x03C7;2 = 4.127, p = 0.042). CONCLUSION: Thrombolysis seems to be equally safe and will achieve an efficacy similar to the efficacy of non-thrombolysis in patients with acute ischemic stroke due to CAD. It is also as effective as thrombolysis in stroke from miscellaneous causes. Therefore, CAD patients experiencing a stroke should not be denied thrombolysis therapy. However, this will need to be confirmed in large-scale randomized studies, especially involving intravenous thrombolysis treatment.

Oxytocin in the regulation of social behaviours in medial amygdala-lesioned mice via the inhibition of the extracellular signal-regulated kinase signalling pathway.

The neuropeptide oxytocin (OXT) has been implicated in the pathophysiology of behavioural deficits among patients with autism spectrum disorder (ASD). However, the molecular mechanisms underlying its role in ASD remain unclear. In the present study, a murine model with ASD-like phenotypes was induced by intra-medial amygdala injection of N-methyl-d-aspartate, and it was used to investigate the role of OXT in behaviour regulation. Behavioural tests were performed to verify the ASD-like phenotypes of N-methyl-d-aspartate-treated mice, and the results showed that mice with bilateral medial amygdala lesions presented significant behavioural deficits, including impaired learning and memory and increased anxiety and depression. We also observed a notably decreased level of OXT in both the plasma and the hypothalamus of medial amygdala-lesioned mice, and the extracellular signal-regulated kinase (ERK) was activated. Further studies demonstrated that the administration of OXT alleviated ASD-like symptoms and significantly inhibited phosphorylation of ERK; the inhibitory effect was similar to that of U0126, an ERK signalling inhibitor. In addition, OXT administration modulated the expression of downstream proteins of the ERK signalling pathway, such as cyclic adenosine monophosphate response element binding and c-fos. Taken together, our data indicate that OXT plays an important role in ameliorating behavioural deficits in an ASD-like mouse model, which was mediated by inhibiting the ERK signalling pathway and its downstream proteins.

The effect of procyanidin on expression of STAT1 in type 2 diabetes mellitus SD rats with focal cerebral ischemia.

OBJECTIVES: Diabetes with cerebral infarction is a common disease that severely impacts health. This study investigated the effect of procyanidin (PC) on the expression of signal transducers and activators of transcription (STAT1) in type 2 diabetes mellitus SD rats with focal cerebral ischemia. We then explored the protective mechanisms of PC in type 2 diabetes mellitus SD rats with focal cerebral ischemia, to provide theory evidence for its clinical application. METHODS: We set up a type 2 diabetes mellitus-MCAO model, evaluated neurological function, and used immunohistochemistry methods to measure the activity of STAT1. RESULTS: The brain expression of STAT1 in rats of the sham-operation group was low, but more STAT1 positive cells were found in normal rats with ischemia and in rats with both type 2 diabetes and ischemia when groups were compared with the sham-operation group (p<0.01). Compared with rats that had type 2 diabetes and ischemia, the numbers of STAT1 positive cells after low, medium and high-doses of PC were all decreased (p<0.01), whereby the mid and high-dose groups showed a more substantial decrease (p<0.01) and with no variance between the two groups (p>0.05). CONCLUSIONS: These results indicate that PC has a neuroprotective effect on type 2 diabetes mellitus-MCAO; this may be through decreasing the expression of STAT1, which influences the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway that may inhibit apoptosis to relieve neurological impairment.

Single-Cell Mapping of Brain Myeloid Cell Subsets Reveals Key Transcriptomic Changes Favoring Neuroplasticity after Ischemic Stroke.

Interactions between brain-resident and peripheral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ischemia. However, conventional bulk sequencing makes it challenging to depict this complex immune network. Using single-cell RNA sequencing, we mapped compositional and transcriptional features of peri-infarct immune cells. Microglia were the predominant cell type in the peri-infarct region, displaying a more diverse activation pattern than the typical pro- and anti-inflammatory state, with axon tract-associated microglia (ATMs) being associated with neuronal regeneration. Trajectory inference suggested that infiltrated monocyte-derived macrophages (MDMs) exhibited a gradual fate trajectory transition to activated MDMs. Inter-cellular crosstalk between MDMs and microglia orchestrated anti-inflammatory and repair-promoting microglia phenotypes and promoted post-stroke neurogenesis, with SOX2 and related Akt/CREB signaling as the underlying mechanisms. This description of the brain's immune landscape and its relationship with neurogenesis provides new insight into promoting neural repair by regulating neuroinflammatory responses.

Constraint-induced movement therapy overcomes the intrinsic axonal growth-inhibitory signals in stroke rats.

BACKGROUND AND PURPOSE: Constraint-induced movement therapy (CIMT) improves functional outcome in patients with stroke possibly through structural plasticity. We hypothesized that CIMT could enhance axonal growth by overcoming the intrinsic growth-inhibitory signals, leading eventually to improved behavioral performance in stroke rats. METHODS: Focal cerebral ischemia was induced by intracerebral injection of endothelin-1. Adult Wistar rats were divided into a sham-operated group, an ischemic group, and an ischemic group treated with CIMT. CIMT started at postoperative day 7 and continued for 3 weeks. Biotinylated dextran amine was injected into the contralateral sensorimotor cortex at postoperative day 14 to trace crossing axons at the cervical spinal cord. The expressions of Nogo-A, Nogo receptor, RhoA, and Rho-associated kinase in the peri-infarct cortex, and the expressions of biotinylated dextran amine, growth associated protein-43, synaptophysin, vGlut1, and postsynaptic density-95 in the denervated spinal cord were measured by immunohistochemistry and Western blots. Behavioral recovery was analyzed at postoperative days 29 to 32. RESULTS: Infarct volumes were not different between groups after stroke. CIMT significantly increased the length and the number of midline crossings of contralateral corticospinal axons to the denervated cervical spinal cord. CIMT significantly decreased the expressions of Nogo-A/Nogo receptor and RhoA/Rho-associated kinase in the peri-infarct cortex, and increased the expressions of growth associated protein-43, synaptophysin, vGlut1, and postsynaptic density-95 in the denervated cervical spinal cord. Behavioral performances assessed by the beam-walking test and the water maze test were improved significantly by CIMT. CONCLUSIONS: CIMT promoted poststroke synaptic plasticity and axonal growth at least partially by overcoming the intrinsic growth-inhibitory signaling, leading to improved behavioral outcome.

New innovations and educational process in undergraduate neurology education in blended learning.

Many undergraduate students suffer from 'neurophobia,' which refers to a lack of knowledge or confidence in neurology, and this can influence their career choices. Various measures have been taken to address this issue, including the implementation of new technologies and methodologies. Significant advancements have been made in the development of blended learning, and the integration of student-centered learning modules, multimedia, and web-based devices has become a common teaching approach. Nonetheless, the optimal delivery form, as well as assessment for the selected learning format and teaching quality in both theory and clinical practice, are being investigated. The purpose of this review is to provide a summary of the current understanding of blended learning as well as innovative methods, technologies, and assessments of undergraduate neurology education. It aims to highlight opportunities for implementing a novel, comprehensive learning model with a suitable blended learning method within a framework of customized technology-assessment processes for future neurology classes, encompassing both theoretical and clinical training.

Effect of physical activity on risk of Alzheimer's disease: A systematic review and meta-analysis of twenty-nine prospective cohort studies.

OBJECTIVE: Physical activity (PA) is beneficial in reductions of all-cause mortality and dementia. However, whether Alzheimer's disease (AD) risk is modified by PA remains disputable. This meta-analysis aims to disclose the underlying relationship between PA and incident AD. METHODS: Pubmed, Embase, Cochrane Library, and Web of Science were retrieved from inception to June 2023. Random-effects models were employed to derive the effect size, represented by hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Twenty-nine prospective cohort studies involving 2068,519 participants were included. The pooled estimate showed a favorable effect of PA on AD risk decline (HR 0.72, 95% CI 0.65-0.80). This association remained robust after adjusting for maximum confounders (HR 0.85, 95% CI 0.79-0.91). Subgroup analysis of PA intensity demonstrated an inverse dose-response relationship between PA and AD, effect sizes of which were significant in moderate (HR 0.85, 95% CI 0.80-0.93) and high PA (HR 0.56, 95% CI 0.45-0.68), but not in low PA (HR 0.94, 95% CI 0.77-1.15). Regardless of all participants or the mid-life cohort, the protection of PA against AD appeared to be valid in shorter follow-up (<15 years) rather than longer follow-up (≥15 years). In addition to follow-up, the robustness of the estimates persisted in supplementary meta-analyses, meta-regression analyses, and sensitivity analyses. CONCLUSION: PA intervention reduces the incidence of AD, but merely in moderate to vigorous PA with follow-up of less than 15 years, thus conditionally recommending the popularization of PA as a modifiable lifestyle factor to prevent AD.

Blockade of CCR5 suppresses paclitaxel-induced peripheral neuropathic pain caused by increased deoxycholic acid.

Paclitaxel leads to peripheral neuropathy (paclitaxel-induced peripheral neuropathy [PIPN]) in approximately 50% of cancer patients. At present, there are no effective treatment strategies for PIPN, the mechanisms of which also remain unclear. In this study, we performed microbiome and metabolome analysis of feces and serum from breast cancer patients with different PIPN grades due to paclitaxel treatment. Our analysis reveals that levels of deoxycholic acid (DCA) are highly increased because of ingrowth of Clostridium species, which is associated with severe neuropathy. DCA, in turn, elevates serum level of C-C motif ligand 5 (CCL5) and induces CCL5 receptor 5 (CCR5) overexpression in dorsal root ganglion (DRG) through the bile acid receptor Takeda G-protein-coupled receptor 5 (TGR5), contributing to neuronal hyperexcitability. Consistent with this, administration of CCR5 antagonist maraviroc suppresses the development of neuropathic nociception. These results implicate gut microbiota/bile acids/CCR5 signaling in the induction of PIPN, thus suggesting a target for PIPN treatment.

Hemichorea associated with nonketotic hyperglycemia in a female.

A case of a 61-year-old woman with hemichorea associated with nonketotic hyperglycemia is reported. The typical presentation of this disease is nonketotic hyperglycemia, hemichorea, hyper-intense signal on T1-weighted magnetic resonance imaging (MRI) and high-density on computed tomography (CT) in the contralateral striatum. With good glycemic control, the clinical symptoms disappeared.

Impact of drug treatment and drug interactions in post-stroke epilepsy.

Stroke is a huge burden on our society and this is expected to grow in the future due to the aging population and the associated co-morbidities. The improvement of acute stroke care has increased the survival rate of stroke patients, and many patients are left with permanent disability, which makes stroke the main cause of adult disability. Unfortunately, many patients face other severe complications such as post-stroke seizures and epilepsy. Acute seizures (ASS) occur within 1 week after the stroke while later occurring unprovoked seizures are diagnosed as post-stroke epilepsy (PSE). Both are associated with a poor prognosis of a functional recovery. The underlying neurobiological mechanisms are complex and poorly understood. There are no universal guidelines on the management of PSE. There is increasing evidence for several risk factors for ASS/PSE, however, the impacts of recanalization, drugs used for secondary prevention of stroke, treatment of stroke co-morbidities and antiseizure medication are currently poorly understood. This review focuses on the common medications that stroke patients are prescribed and potential drug interactions possibly complicating the management of ASS/PSE.

Exploring the potential biomarkers for prognosis of glioblastoma via weighted gene co-expression network analysis.

BACKGROUND: Glioblastoma (GBM) is the most common malignant tumor in the central system with a poor prognosis. Due to the complexity of its molecular mechanism, the recurrence rate and mortality rate of GBM patients are still high. Therefore, there is an urgent need to screen GBM biomarkers to prove the therapeutic effect and improve the prognosis. RESULTS: We extracted data from GBM patients from the Gene Expression Integration Database (GEO), analyzed differentially expressed genes in GEO and identified key modules by weighted gene co-expression network analysis (WGCNA). GSE145128 data was obtained from the GEO database, and the darkturquoise module was determined to be the most relevant to the GBM prognosis by WGCNA (r =  - 0.62, p = 0.01). We performed enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to reveal the interaction activity in the selected modules. Then Kaplan-Meier survival curve analysis was used to extract genes closely related to GBM prognosis. We used Kaplan-Meier survival curves to analyze the 139 genes in the darkturquoise module, identified four genes (DARS/GDI2/P4HA2/TRUB1) associated with prognostic GBM. Low expression of DARS/GDI2/TRUB1 and high expression of P4HA2 had a poor prognosis. Finally, we used tumor genome map (TCGA) data, verified the characteristics of hub genes through Co-expression analysis, Drug sensitivity analysis, TIMER database analysis and GSVA analysis. We downloaded the data of GBM from the TCGA database, the results of co-expression analysis showed that DARS/GDI2/P4HA2/TRUB1 could regulate the development of GBM by affecting genes such as CDC73/CDC123/B4GALT1/CUL2. Drug sensitivity analysis showed that genes are involved in many classic Cancer-related pathways including TSC/mTOR, RAS/MAPK.TIMER database analysis showed DARS expression is positively correlated with tumor purity (cor = 0.125, p = 1.07e-02)), P4HA2 expression is negatively correlated with tumor purity (cor =-0.279, p = 6.06e-09). Finally, GSVA analysis found that DARS/GDI2/P4HA2/TRUB1 gene sets are closely related to the occurrence of cancer. CONCLUSION: We used two public databases to identify four valuable biomarkers for GBM prognosis, namely DARS/GDI2/P4HA2/TRUB1, which have potential clinical application value and can be used as prognostic markers for GBM.