Human gestational diabetes mellitus-derived exosomes impair glucose homeostasis in pregnant mice and stimulate functional maturation of offspring-islets.

AIMS: Pancreatic islets undergo critical development and functional maturation during the perinatal period when they are highly sensitive to microenvironment. We aim to determine the effects and mechanisms of gestational diabetes mellitus (GDM) hypermetabolic stress on glucose homeostasis in pregnant mice and functional maturation of the islets of their offspring. MAIN METHODS: Exosomes were extracted from the umbilical vein blood of individuals with or without GDM for administration to pregnant mice. The blood glucose, serum insulin, glycosylated hemoglobin, and lipopolysaccharide levels were measured in pregnant mice. The expression and localization of insulin, glucagon, PC1/3, PDX1, and p-S6 in the islets of neonatal rats were continuously monitored using immunofluorescence to evaluate their functional status. Primary islet cells were cultured and treated with GDM exosomes and exendin to determine the expression of GLP-1R, AKT, p-AKT, and p-S6 via western blotting. KEY FINDINGS: GDM exosomes induced remarkable oral glucose intolerance, hyperinsulinemia, and metabolic inflammation in pregnant mice. The islets of GDM offspring exhibited high insulin, glucagon, PC1/3, PDX1, and p-S6 expression at and after birth, and activation of the local GLP-1/GLP-1R axis. The functional maturation of normal-offspring islets did not commence until after birth, while it was activated prior to birth in GDM offspring, seriously disrupting the whole process. GDM exosomes activated the GLP-1/GLP-1R axis between α and ß cells, and stimulated functional maturation of ß cells via the Akt-mTORC1-pS6 pathway. SIGNIFICANCE: These findings provide preliminary insights into the mechanisms underlying the high incidence of diabetes in the offspring of mothers with GDM.

Melatonin as an add-on treatment for epilepsy: A systematic review and meta-analysis.

PURPOSE: Epilepsy, one severe prevalent brain disorder, primarily relies on drug treatment. However, approximately one-third of patients with epilepsy do not achieve effective control with current medications, underscoring the need for more innovative treatment approaches. Notably, melatonin has gained attention for its anti-seizure properties and favourable safety profile. This systematic review aimed to evaluate the efficacy and safety of melatonin as an add-on treatment for epilepsy. METHODS: We searched for articles published before June 2023 in Web of Science, Cochrane Library, and PubMed. We used RevMan 5.4 software to compute relative risks (RRs) and 95 % confidence intervals (CIs). Key outcomes included total sleep time, wakefulness after sleep onset, sleep latency, seizure frequency, seizure severity, and safety. The quality of randomised controlled studies (RCTs) was assessed using the Cochrane Risk of Bias tool. RESULTS: Of the 264 publications retrieved, 10 RCTs were included in the meta-analysis. Add-on melatonin treatment improved sleep latency (RR: 0.56; 95 %CI: 0.10-1.02; P = 0.02) and seizure severity (RR: 0.33; 95 %CI: 0.04-0.62; P = 0.03) compared with placebo treatment. Adverse events (increased headache severity in children with a history of migraines, bronchitis, ear infections, agitation, and urinary frequency) were reported in only one trial. CONCLUSION: This systematic review found that add-on melatonin therapy improved sleep latency and seizure severity in patients with epilepsy. However, several of the included studies did not systematically assess sleep quality, seizures, and safety and lacked long-term follow-up data. Further RCTs with extended follow-up periods are required to definitively determine the efficacy and safety of melatonin.

Association between Sleep and Alzheimer's Disease: A Bibliometric Analysis from 2003 to 2022.

INTRODUCTION: Alzheimer's disease (AD) often presents with sleep disorders, which are also an important risk factor for AD, affecting cognitive function to a certain extent. This study aimed to reveal the current global status, present hotspots, and discuss emerging trends of sleep and AD using a bibliometric approach. METHODS: Research and review articles related to sleep and AD from 2003 to 2022 were extracted from the Web of Science Core Collection. VOSviewer 1.6.18.0, Scimago Graphica, and CiteSpace 6.2.R2 were used to map the productive and highly cited countries, institutions, journals, authors, references, and keywords in the field. RESULTS: Overall, 4,008 publications were included in this bibliometric analysis. The number of publications and citations showed an increasing trend over the past two decades. The USA and China had the largest and second largest, respectively, number of publications and citations and cooperated with other countries more closely. Ancoli-Israel Sonia published the most papers, and Holtzman David M was co-cited most frequently. The most productive journal was Journal of Alzheimer's Disease, and Neurology was the most frequently cited journal. The risk factors, ß-amyloid (Aß), tau, neuroinflammation, astrocytes, glymphatic system, orexin, functional connectivity, and management have been the main research directions of researchers over the past few years and may be the future trend of valuable research. CONCLUSION: We identified hotspots and emerging trends including risk factors, Aß, tau, neuroinflammation, the glymphatic system, orexin, and management, which may help identify new therapeutic targets and improve clinical efficacy of sleep and AD.

Tenecteplase vs. Alteplase for Intravenous Thrombolytic Therapy of Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

INTRODUCTION: In recent years, as one of the drugs for the treatment of acute ischemic stroke (AIS), the clinical application of tenecteplase is still controversial. Therefore, we aimed to evaluate the safety and efficacy of tenecteplase versus alteplase to guide clinical practice. METHODS: A search of PubMed, MEDLINE, EMBASE, Cochrane Library, and Web of Science databases until February 15, 2023 was conducted to identify eligible articles. The quality of the included studies was assessed using the Cochrane Risk of Bias tool. RevMan 5.3 and Stata 17 were used to perform the meta-analysis and detect publication bias, and risk ratios (RRs) with 95% confidence intervals (95% CIs) were reported for each outcome measure. RESULTS: A total of 1326 records were retrieved in this meta-analysis. As a result of the limited reports on tenecteplase in patients with AIS and the lack of high-quality randomized controlled trials (RCTs), and considering the impact of publication bias, we did not include any of these studies published before 2015. Ultimately we included 16 RCTs with a total of 7508 patients, including 3940 patients treated with alteplase and 3568 patients treated with tenecteplase. Tenecteplase was associated with better early neurological improvement (RR 0.10; 95% CI 0.00-0.19; P = 0.04), recanalization of blood vessels (RR 0.24; 95% CI 0.07-0.40; P = 0.01), and 90-day excellent neurological recovery (RR 0.12; 95% CI 0.01-0.24; P = 0.04). In addition, there were no significant differences in other efficacy and safety outcomes between the two groups. The funnel plot and Begg's as well as Egger's tests showed no significant publication bias. CONCLUSIONS: This meta-analysis showed that tenecteplase was not inferior to alteplase in early thrombolytic therapy in patients with AIS, and was even better than alteplase on some efficacy outcomes with no significant differences in safety. However, as a result of some inherent limitations of this study, more high-quality prospective clinical studies are needed to confirm these results.

In recent years, there has been controversy surrounding the use of tenecteplase, a drug for treating acute ischemic stroke (AIS). To help doctors make better decisions, we compared the safety and effectiveness of tenecteplase with another drug called alteplase. We looked at various research articles from PubMed, MEDLINE, EMBASE, Cochrane Library, and Web of Science databases until February 15, 2023. After careful analysis, we found 16 relevant studies with a total of 7508 patients, including those treated with alteplase and tenecteplase. Our findings showed that tenecteplase was as effective as alteplase in providing early thrombolytic therapy for patients with AIS. In fact, tenecteplase even showed better results in some aspects of treatment, without compromising safety. However, we acknowledge some limitations in our study and recommend more high-quality clinical studies to validate these results.

Risk assessment model for sleep disturbance based on gastrointestinal myoelectrical activity in middle-aged and elderly people.

Background: Sleep disturbance has become a considerable factor affecting the quality of life for middle-aged and elderly people; however, there are still many obstacles to screening sleep disturbance for those people. Given the growing awareness of the association between gastrointestinal function and sleep disturbance, our study aims to predict the risk of sleep disturbance using gastrointestinal electrophysiological signals. Methods: The Pittsburgh Sleep Quality Index and gastrointestinal electrophysiological signals of 914 participants in western China were used to establish the model. Demographic characteristics and routine blood test were collected as covariates. Participants were randomly assigned into two sets with a 7:3 ratio for training and validation. In the training set, the least absolute shrinkage and selection operator (LASSO) regression and stepwise logistic regression were used, respectively for variables selection and optimization. To assess the model performance, receiver operator characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were utilized. Then, validation was performed. Results: Thirteen predictors were chosen from 46 variables by LASSO regression. Then, age, gender, percentage of normal slow wave and electrical spreading rate on the pre-meal gastric channel, dominant power ratio on the post-meal gastric channel, coupling percent and dominant frequency on the post-meal intestinal channel were the seven predictors reserved by logistic regression. The area under ROC curve was 0.65 in the training set and 0.63 in the validation set, both exhibited moderate predictive ability. Furthermore, by overlapping the DCA results of two data-sets, there might be clinical net benefit if 0.35 was used as reference threshold for high risk of sleep disturbance. Conclusion: The model performs a worthy predictive potency for sleep disturbance, which not only provides clinical evidence for the association of gastrointestinal function with sleep disturbance, but also can be considered as an auxiliary assessment for screening sleep disturbance.

A bibliometric analysis of cerebral microbleeds and cognitive impairment.

BACKGROUND AND OBJECTIVES: Cerebral microbleeds (CMBs) are imaging markers for small cerebral vascular diseases, which can accumulate and impact the corresponding brain networks. CMBs can affect cognitive function, including executive function, information processing speed, and visuospatial memory. Bibliometrics is a scientific and innovative method that can analyze and visualize the scientific field quantitatively. In this study, we aimed to use bibliometric analysis to demonstrate the relationship and mechanisms between CMBs and cognitive impairment. Furthermore, we reviewed the relationship between CMBs and different cognitive disorders. The use of bibliometrics can help further clarify this relationship. METHODS: We retrieved articles on CMBs and cognitive impairment from the Web of Science Core Collection. The keywords (such as stroke, dementia, and cerebral amyloid angiopathy), authors, countries, institutions and journals, in the field were visually analyzed using VOSviewer software and bibliometric websites. RESULTS: This bibliometric analysis reveals the related trends of CMBs in the field of cognitive impairment. CMBs, along with other small vascular lesions, constitute the basis of cognitive impairment, and studying CMBs is essential to understand the mechanisms underlying cognitive impairment. CONCLUSION: This bibliometric analysis reveals a strong link between CMBs and cognitive impairment-related diseases and that specific brain networks were affected by CMBs. This provides further insights into the possible mechanisms and causes of CMBs and cognitive impairment. The direct and indirect damage (such as oxidative stress and neuroinflammation) to the brain caused by CMBs, destruction of the frontal-subcortical circuits, elevated Cystatin C levels, and iron deposition are involved in the occurrence and development of cognitive impairment. CMBs may be a potential marker for detecting, quantifying, and predicting cognitive impairment.

Loss of TDP-43 promotes somatic CAG repeat expansion in Huntington's disease knock-in mice.

TAR binding protein 43 (TDP-43) is normally present in the nucleus but mislocalized in the cytoplasm in a number of neurodegenerative diseases including Huntington's disease (HD). The nuclear loss of TDP-43 impairs gene transcription and regulation. However, it remains to be investigated whether loss of TDP-43 influences trinucleotide CAG repeat expansion in the HD gene, a genetic cause for HD. Here we report that CRISPR/Cas9 mediated-knock down of endogenous TDP-43 in the striatum of HD knock-in mice promoted CAG repeat expansion, accompanied by the increased expression of the DNA mismatch repair genes, Msh3 and Mlh1, which have been reported to increase trinucleotide repeat instability. Furthermore, suppressing Msh3 and Mlh1 by CRISPR/Cas9 targeting diminished the CAG repeat expansion. These findings suggest that nuclear TDP-43 deficiency may dysregulate the expression of DNA mismatch repair genes, leading to CAG repeat expansion and contributing to the pathogenesis of CAG repeat diseases.

Bioinformatics-based analysis of mechanistic differences in vascular endothelial injury ischemic stroke induced by atrial fibrillation and atherosclerosis.

Studies of the intracranial vasculature in patients with ischemic stroke caused by atherosclerosis (AS) and cardiac embolism have revealed significantly different degrees of AS, plaque, and vascular stenosis. And the endothelium has a great influence on the vasculature throughout the circulatory system, especially in the brain. This study aimed to investigate the mechanistic differences in endothelial injury between atrial fibrillation (AF)- and AS-induced ischemic stroke. All target genes of AF, AS, and the vascular endothelial cell (VC) were obtained from the GeneCards database; the differential genes of AF and AS separately associated with the VC were established by a Venn diagram. A protein-protein interaction network was created, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases were used to perform genomic enrichment and functional enrichment analysis. Hub genes were selected by Maximal Clique Centrality algorithm ranking and correlation linkage in the STRING database, and then, clinical serum samples were used to verify the quantitative expressions in the AF, AF stroke, AS, and AS stroke groups. Fifty-five AF-VC-related genes and ninety-three AS-VC-related genes were screened, which differed in biological function, cellular composition, and molecular function. The genes correlation between AF and vascular endothelial cells (VCs) was KRAS and PTPN11, and those correlation between AS and VCs was IL-4, IFNG, IL-17A, and CSF-2. IL-4 and CSF-2 may be relevant proteins involved in the differences in stroke mechanisms between AF and AS, and they may act by further influencing the function of their downstream cells. This study provides a preliminary theoretical basis for investigating the differences in mechanisms of endothelial injury between AF- and AS-induced ischemic stroke.

Ketogenic diet alleviates brain iron deposition and cognitive dysfunction via Nrf2-mediated ferroptosis pathway in APP/PS1 mouse.

Progressive cognitive decline and increased brain iron deposition with age are important features of Alzheimer's disease. Previous studies have found that the short-term ketogenic diet has neuroprotective effects in a variety of neurodegenerative diseases, but the effects of an early and long-term ketogenic diet on brain iron content and cognition of Alzheimer's disease have not been reported. In our study, 8-week-old APP/PS1 mice were given a 12-month ketogenic or standard diet, while C57BL/6 mice matched with the age and genetic background of APP/PS1 mice were used as normal controls to be given a standard diet for the same length of time. We found that 12 months of an early ketogenic diet improved the impaired learning and memory ability of APP/PS1 mice. The improvement of cognitive function may be related to the reduction of amyloid-beta deposition and neuronal ferroptosis. The mechanism was achieved by the regulation of ferroptosis-related pathways after activation of nuclear factor erythroid 2-related factor 2 by ketogenic diet-induced elevated ß-hydroxybutyrate. In addition, blood biochemical results showed that compared with the standard diet group of the disease, although the early and long-term ketogenic diet increased blood lipids to some extent, it seemed to reduce liver, renal, and myocardial damage caused by genetic differences. This will provide a piece of positive evidence for the early and long-term use of ketogenic diets in people at risk of Alzheimer's disease.

A novel full solar light spectrum responsive antimicrobial agent of WS2 quantum dots for photocatalytic wound healing therapy.

Photocatalytic antimicrobial therapy (PCAT) is considered to be a potential therapeutic treatment for bacterial-infection diseases. However, the antibacterial efficiency is unsatisfactory due to the limited application scope of photocatalysis. In this work, full-spectrum responsive tungsten disulfide quantum dots (WS2 QDs) are prepared for killing bacteria and enabling wound healing through photocatalytic reactive oxygen species (ROS) generation and glutathione (GSH) depletion. On the one hand, these ultrasmall WS2 QDs exhibit an excellent full spectrum (UV-Vis-NIR)-responsive photocatalytic effect by hindering the recombination of electron-hole pairs, thereby achieving the full use of the energy spectrum. Furthermore, the full-spectrum photocatalytic property of the as-prepared WS2 QDs can be effectively strengthened by redox reaction to deplete GSH for accelerated wound healing. In a word, the as-prepared nanoplatform exhibits the ability to act as an admirable antibacterial reagent with full-spectrum catalytic performance for photocatalytic wound healing therapy. Therefore, this work will not only provide an effective full-spectrum photocatalytic reagent for anti-bacteria therapy and wound healing, but also provide a rational idea for the development of other novel antibacterial agents for applications in the biomedical field.

Neuroprotective Role of MiRNA-9 in Neurological Diseases: A Mini Review.

MicroRNAs (miRNAs) are a class of non-coding small RNAs with about 22 nucleotides in eukaryotes. They regulate gene expression at the post-transcriptional level and play a key role in physiological and pathological processes. As one of the most abundant miRNAs in the human brain, miRNA-9 (miR-9) has attracted extensive attention due to its important role in the maintenance of normal function of the nervous system and the occurrence and development of nervous system diseases. Hence, we reviewed the neuroprotective effect of miR-9 in neurological diseases. MiR-9 may be a potential target of nervous system diseases.

A Meta-analysis of Randomized Controlled Trials Comparing the Efficacy and Safety of Pregabalin and Gabapentin in the Treatment of Postherpetic Neuralgia.

OBJECTIVE: To systematically evaluate the clinical efficacy of pregabalin and gabapentin in the treatment of postherpetic neuralgia (PHN), including the difference in pain control and occurrence of adverse reactions. METHODS: PubMed, MEDLINE, EMBASE, Cochrane Library, and Web of Science databases were searched for randomized controlled trials (RCTs) comparing the efficacy of pregabalin and gabapentin in patients with PHN. Data from studies meeting the inclusion criteria were extracted and the Cochrane Risk of Bias risk assessment tool was used to evaluate the quality of the included studies. Revman 5.3 and Stata17 were used to perform the meta-analysis and to detect publication bias. RESULTS: A total of 14 RCTs with 3545 patients were included in this study, including 926 in the pregabalin treatment group, 1256 in the gabapentin treatment group, and 1363 in the placebo control group. Pregabalin was better than gabapentin in alleviating pain and improving the global perception of change in pain and sleep (P < 0.05). Gabapentin was associated with a lower incidence of adverse events than pregabalin (P < 0.05). Funnel plot and Begg's and Egger's tests showed no significant publication bias. CONCLUSION: Pregabalin appears to have a better overall therapeutic effect than gabapentin for patients with PHN, but gabapentin has a lower incidence of adverse reactions and a better safety profile. Clinicians should comprehensively consider patient factors and fully evaluate the advantages and disadvantages of each treatment option to select the most suitable drugs for patient use. Considering the limited quantity and quality of the existing literature, high-quality RCTs are needed to confirm the advantages of pregabalin over gabapentin in the treatment of PHN and guide clinical decision-making.

Bioinformatics and network pharmacology analysis of drug targets and mechanisms related to the comorbidity of epilepsy and migraine.

OBJECTIVE: The present study aimed to explore the mechanisms underlying the comorbidity of epilepsy and migraine, identify potential common targets for drug intervention, and provide insight into new avenues for disease prevention and treatment using an integrated bioinformatic and network pharmacology approach. METHODS: Disease targets in epilepsy and migraine were screened using the DisGeNET database to identify intersecting gene targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEEG) enrichment analyses were then performed using the WebGestalt database. Furthermore, the STRING database was used to construct a protein-protein interaction (PPI) network, and Cytoscape software was used to analyze the protein molecular signals at the intersection of epilepsy and migraine. The Drugbank database was used to identify common targets for antiepileptic drugs in epilepsy and migraine to further analyze the disease-gene-target-drug interaction network. Finally, molecular docking simulations were performed to verify the hypothesis that migraine and epilepsy share common diseases and drug targets. RESULTS: A total of 178 common targets for epilepsy and migraine were identified using the DisGeNET database, and the 24 genes most related to the diseases were screened using the Score_gda gene scoring system. GO enrichment analysis indicated that common targets were mainly enriched in biological processes and molecular functions, including membrane potential regulation, inorganic ion transmembrane transport, axonal signaling, and ion channel activity. KEGG pathway enrichment analysis indicated that the mechanism of action might be related to neuroactive ligand receptors, AGE-RAGE, cAMP, and VEGF signaling pathways. The PPI network construction and analysis results showed that the PPI grid had 23 central nodes and 24 connected edges, with an average node degree of 2.09 and an average clustering coefficient of 0.384. The 10 genes with potentially important roles in epilepsy and migraine were CACNA1A, KCNQ2, KCNA1, SCN1A, PRRT2, SCN8A, KCNQ3, SCN2A, GRIN2A, and GABRG2. Drugbank database results indicated that antiepileptic drugs, including lamotrigine, topiramate, valproic acid, carbamazepine, gabapentin, and perampanel, also had common targets with migraine. The three most important targets exhibited strong binding affinity with drugs in the molecular docking simulations. CONCLUSION: Our systematic and comprehensive analyses of disease-gene-target-drug interaction networks identified several biological processes and molecular functions common to migraine and epilepsy, most of which were related to neuroactive ligand-receptor interactions. These data provide a new theoretical basis and reference for the clinical treatment of comorbid epilepsy and migraine and may aid in the development of novel pharmacological strategies.

The efficacy and safety of third-generation antiseizure medications and non-invasive brain stimulation to treat refractory epilepsy: a systematic review and network meta-analysis study.

Background: The new antiseizure medications (ASMs) and non-invasive brain stimulation (NIBS) are controversial in controlling seizures. So, this network meta-analysis aimed to evaluate the efficacy and safety of five third-generation ASMs and two NIBS therapies for the treatment of refractory epilepsy. Methods: We searched PubMed, EMBASE, Cochrane Library and Web of Science databases. Brivaracetam (BRV), cenobamate (CNB), eslicarbazepine acetate (ESL), lacosamide (LCM), perampanel (PER), repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS) were selected as additional treatments for refractory epilepsy in randomized controlled studies and other cohort studies. Randomized, double-blind, placebo-controlled, add-on studies that evaluated the efficacy or safety of medication and non-invasive brain stimulation and included patients with seizures were uncontrolled by one or more concomitant ASMs were identified. A random effects model was used to incorporate possible heterogeneity. The primary outcome was the change in seizure frequency from baseline, and secondary outcomes included the proportion of patients with ≥50% reduction in seizure frequency, and the rate of treatment-emergent adverse events. Results: Forty-five studies were analyzed. The five ASMs and two NIBS decreased seizure frequency from baseline compared with placebo. The 50% responder rates of the five antiseizure drugs were significantly higher than that of placebo, and the ASMs were associated with fewer adverse events than placebo (p < 0.05). The surface under the cumulative ranking analysis revealed that ESL was most effective in decreasing the seizure frequency from baseline, whereas CNB provided the best 50% responder rate. BRV was the best tolerated. No significant publication bias was identified for each outcome index. Conclusion: The five third-generation ASMs were more effective in controlling seizures than placebo, among which CNB, ESL, and LCM were most effective, and BRV exhibited better safety. Although rTMS and tDCS did not reduce seizure frequency as effectively as the five drugs, their safety was confirmed. Systematic review registration: PROSPERO, https://www.crd.york.ac.uk/prospero/ (CRD42023441097).

The effect of blood pressure variability on the prognosis of patients with acute cerebral hemorrhage: Possible mechanism.

Background: Antihypertensive therapy in the acute phase of intracerebral hemorrhage (ICH) can reduce hematoma expansion. Numerous studies have demonstrated that blood pressure variability secondary to antihypertensive therapy has adverse effects on neurological outcomes, but the conclusions are diverse, and the mechanism of this occurrence is unknown. The aim of this research was to analyze the impact of blood pressure variability after antihypertensive treatment on the prognosis of patients with acute ICH, along with the possible mechanism. Materials and methods: A total of 120 patients within 20 h of onset of ICH were divided into a good prognosis group (mRS ≤ 2 points) and a poor prognosis group (mRS ≥ 3 points) according to their 90-day mRS scores. The basic patient information, NIHSS score, GCS score, mRS score at 90 days after admission, head CT examination at admission and 24 h and CTP examination at 24 h were collected from some patients. The blood pressure values of patients were collected within 24 h, and multiple blood pressure variation (BPV) parameters within 1 and 24 h were calculated. Results: (1) After excluding confounding factors such as age, whether the hematoma ruptured into the ventricle, confounding signs, amount of bleeding, edema around the hematoma, NIHSS on admission, operation or non-operation, and 24-h hematoma increment, the fourth quartile systolic blood pressure (SBP) maximum and minimum difference within 1 h [OR: 5.069, CI (1.036-24.813) P = 0.045] and coefficient of continuous variation (SV) within 24 h [OR: 2.912 CI (1.818-71.728) P = 0.009] were still independent factors affecting the 90-day mRS in ICH patients. (2) There was a negative correlation between SBP SV and CBF in terms of the difference between the contralateral side and the perihematomal region at 24 h (Rs = -0.692, P = 0.013). Conclusion: Blood pressure variability after antihypertensive therapy in acute ICH is one of the influencing factors for 90-day mRS in patients. A 1-h dramatic drop in SBP and 24-h SBP SV may affect the long-term prognosis of patients by reducing whole cerebral perfusion.

A bibliometric analysis of the recent advances in diazepam from 2012 to 2021.

Background: Diazepam is a classic benzodiazepine drug that has been widely used for disorders such as anxiety, sleep disorders, and epilepsy, over the past 59 years. The study of diazepam has always been an important research topic. However, there are few bibliometric analyses or systematic studies in this field. This study undertook bibliometric and visual analysis to ascertain the current status of diazepam research, and to identify research hotspots and trends in the past 10 years, to better understand future developments in basic and clinical research. Methods: Articles and reviews of diazepam were retrieved from the Web of Science core collection. Using CiteSpace, VOSviewer, and Scimago Graphica software, countries, institutions, authors, journals, references, and keywords in the field were visually analyzed. Results: A total of 3,870 publications were included. Diazepam-related literature had high volumes of publications and citations. The majority of publications were from the USA and China. The highest number of publications and co-citations, among the authors, was by James M Cook. Epilepsia and the Latin American Journal of Pharmacy were the journals with the most publications on diazepam and Epilepsia was the most frequently cited journal. Through a comprehensive analysis of keywords and references, we found that current research on diazepam has focused on its mechanism of action, application in disease, pharmacokinetics, risk, assessment, and management of use, status epilepticus, gamma-aminobutyric acid receptors (GABAR), intranasal formulation, gephyrin, and that ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) is the current research hotspot. Conclusion: Research on diazepam is flourishing. We identified research hotspots and trends in diazepam research using bibliometric and visual analytic methods. The clinical applications, mechanisms of action, pharmacokinetics, and assessment and management of the use of diazepam are the focus of current research and the development trend of future research.

Effect of vertebrobasilar dolichoectasia on endovascular therapy in acute posterior circulation infarction.

Background and purpose: This study aimed to analyze the feasibility and safety of endovascular therapy (EVT) in patients with acute posterior circulation stroke and vertebrobasilar dolichoectasia (VBD). Materials and methods: BASILAR was a national prospective registry of consecutive patients with symptomatic and imaging-confirmed acute stroke in the posterior circulation within 24 h of symptom onset. We evaluated EVT feasibility and safety in patients with VBD. Primary outcomes included improvement in modified Rankin Scale scores (mRS) at 90 days and mortality within 90 days. The secondary outcome was the rate of favorable functional outcome, defined as mRS ≤ 3 (indicating independent ambulation) at 90 days. Safety outcomes included surgery-related complications and other serious adverse events. Results: A total of 534 cases were included: 159 with VBD and 375 controls. No significant difference in mRS at 90 days was found between groups, but patients with VBD had a higher baseline National Institutes of Health Stroke Scale (NIHSS) score [30 (19-33) vs. 25 (15-32)] and were older [65 (59-74) vs. 63 (55-72) year]. After propensity score matching, there were no significant differences in baseline NIHSS score between the two groups, and the efficacy and safety of EVT were similar between patients with or without VBD. Furthermore, the prognostic effect of puncture-to-recanalization time on the probability of mortality within 90 days in EVT-treated patients with VBD was significant {adjusted odds ratio, 1.008 [95% confidence interval (1.001-1.015)]}. Conclusion: Endovascular therapy is safe and feasible in patients with acute posterior circulation stroke and VBD. The puncture-to-recanalization time is important for predicting the prognosis of EVT-treated patients with VBD.

CXCL14 exacerbates seizures by inhibiting GABA metabolism in epileptic mice.

OBJECTIVE: Epilepsy is a common central nervous system disorder with pathological mechanisms including inflammation, ion channel impairment, and neurotransmitter imbalance. Despite the rapid development of current anti-epileptic drugs, epilepsy is not well controlled, so there is still a need for research on the mechanisms and new drug targets for epilepsy. CXCL14 is a member of the CXC family of chemokines, and its receptor is currently unknown. Chemokines are the third major communication mediators in the central nervous system and play a role in many diseases. Therefore, we explore the expression of CXCL14 in epilepsy and its possible mechanisms. MATERIALS AND METHODS: We chose the kainic acid (KA) mouse model as the epilepsy model, and studied the expression of CXCL14 in this model by western blot. Subsequently, after knocking down CXCL14, we explored the effect of CXCL14 on seizures by electrophysiology and FJB (Fluoro-Jade B) staining. Western blot and ELISA were used to explore the possible mechanism of CXCL14 affecting seizures. RESULTS: CXCL14 expression gradually increased after a seizure until it peaked at 72 hours and then gradually decreased again. The knockdown of CXCL14 resulted in prolonged seizure latency, decreased seizure grade, and reduced degenerative necrosis of neurons in mice. Levels of GABA (γ-aminobutyric acid), GAD67 (glutamate decarboxylase 67) and GABAA receptor (γ-aminobutyric acid A receptor) were increased. CONCLUSION: Our results suggest that CXCL14 expression is increased after seizures and may exacerbate seizures by regulating GABA metabolism. Based on this, CXCL14 could be a new target for epilepsy treatment and antiepileptic drug development.

Tumor microenvironment-activated single-atom platinum nanozyme with H2O2 self-supplement and O2-evolving for tumor-specific cascade catalysis chemodynamic and chemoradiotherapy.

Nanozyme-based tumor collaborative catalytic therapy has attracted a great deal of attention in recent years. However, their cooperative outcome remains a great challenge due to the unique characteristics of tumor microenvironment (TME), such as insufficient endogenous hydrogen peroxide (H2O2) level, hypoxia, and overexpressed intracellular glutathione (GSH). Methods: Herein, a TME-activated atomic-level engineered PtN4C single-atom nanozyme (PtN4C-SAzyme) is fabricated to induce the "butterfly effect" of reactive oxygen species (ROS) through facilitating intracellular H2O2 cycle accumulation and GSH deprivation as well as X-ray deposition for ROS-involving CDT and O2-dependent chemoradiotherapy. Results: In the paradigm, the SAzyme could boost substantial ∙OH generation by their admirable peroxidase-like activity as well as X-ray deposition capacity. Simultaneously, O2 self-sufficiency, GSH elimination and elevated Pt2+ release can be achieved through the self-cyclic valence alteration of Pt (IV) and Pt (II) for alleviating tumor hypoxia, overwhelming the anti-oxidation defense effect and overcoming drug-resistance. More importantly, the PtN4C-SAzyme could also convert O2·- into H2O2 by their superior superoxide dismutase-like activity and achieve the sustainable replenishment of endogenous H2O2, and H2O2 can further react with the PtN4C-SAzyme for realizing the cyclic accumulation of ∙OH and O2 at tumor site, thereby generating a "key" to unlock the multi enzymes-like properties of SAzymes for tumor-specific self-reinforcing CDT and chemoradiotherapy. Conclusions: This work not only provides a promising TME-activated SAzyme-based paradigm with H2O2 self-supplement and O2-evolving capacity for intensive CDT and chemoradiotherapy but also opens new horizons for the construction and tumor catalytic therapy of other SAzymes.