Thrombolysis increases the risk of persistent headache attributed to ischemic stroke: A prospective observational study.

BACKGROUND AND OBJECTIVE: Persistent headache attributed to ischemic stroke (PHPIS) is increasingly acknowledged and was added to the 2018 ICHD-3. Intravenous thrombolysis (IVT) is a common treatment for acute ischemic stroke. It remains unknown whether this treatment influences the occurrence of a persistent poststroke headache. We aimed to describe the incidence and clinical characteristics of persistent headaches occurring after acute ischemic stroke in patients with or without IVT and explore the risk factors. METHODS: A prospective observational study was performed between the 234 individuals who received IVT and 226 individuals without IVT in 5 stroke units from Wuhan, China. Subjects were followed for 6 months after stroke via a structured questionnaire. RESULTS: Age, gender, vascular risk factors, and infarct location/ circulation distribution did not differ between the groups, although IVT group had higher initial NIHSS scores. At the end of the follow-up, 12.0% (55/460) of subjects reported persistent headaches after ischemic stroke. The prevalence of persistent headache was significantly higher in the IVT group than non-IVT group (15.4% vs. 8.4%, p = .021). Patients with younger age (p = .033; OR 0.97; 95% CI 0.939-0.997), female sex (p = .007; OR 2.40; 95% CI 1.269-4.520), posterior circulation infarct (p = .024; OR 2.19; 95% CI 1.110-4.311), and IVT (p = .005; OR 2.51; 95% CI 1.313-4.782) were more likely to develop persistent headache after ischemic stroke. CONCLUSION: The potential influence of IVT should be considered when assessing persistent poststroke headache. Future studies will investigate the underlying mechanisms.

Profile of Chinese Cluster Headache Register Individual Study (CHRIS): Clinical characteristics, diagnosis and treatment status data of 816 patients in China.

BACKGROUND: The clinical profile of cluster headache may differ among different regions of the world, warranting interest in the data obtained from the initial Chinese Cluster Headache Register Individual Study (CHRIS) for better understanding. METHODS: We conducted a multicenter, prospective, longitudinal cohort study on cluster headache across all 31 provinces of China, aiming to gather clinical characteristics, treatment approaches, imaging, electrophysiological and biological samples. RESULTS: In total 816 patients were enrolled with a male-to-female ratio of 4.33:1. The mean age at consultation was 34.98 ± 9.91 years, and 24.89 ± 9.77 years at onset. Only 2.33% were diagnosed with chronic cluster headache, and 6.99% had a family history of the condition. The most common bout was one to two times per year (45.96%), lasting two weeks to one month (44.00%), and occurring frequently in spring (76.23%) and winter (73.04%). Of these, 68.50% experienced one to two attacks per day, with the majority lasting one to two hours (45.59%). The most common time for attacks was between 9 am and 12 pm (75.86%), followed by 1 am and 3 am (43.48%). Lacrimation (78.80%) was the most predominant autonomic symptom reported. Furthermore, 39.22% of patients experienced a delay of 10 years or more in receiving a correct diagnosis. Only 35.67% and 24.26% of patients received common acute and preventive treatments, respectively. CONCLUSION: Due to differences in ethnicity, genetics and lifestyle conditions, CHRIS has provided valuable baseline data from China. By establishing a dynamic cohort with comprehensive multidimensional data, it aims to advance the management system for cluster headache in China.

Type A personality, sleep quality, and cerebral small vessel disease: investigating the mediating role of sleep in a community-based study.

Purpose: Type A behavior pattern (TABP) is a personality type characterized by rapid speech, impatience, competition, and hostility. Asymptomatic cerebral small vessel disease (CSVD) is often endemic in older adults. Individuals with TABP commonly experience suboptimal sleep quality, and a correlation exists between sleep disturbances and CSVD. We investigated the relationship between TABP and CSVD markers and further explored the mediating role of sleep quality in the relationship between TABP and CSVD. Methods: A cross-sectional survey included 764 community-dwelling adults aged 55-85 years. The TABP Scale and the Pittsburgh Sleep Quality Index (PSQI) were used to assess personality and sleep quality, respectively. Linear and logistic regression analyses were used to examine relationships between variables of interest. In addition, mediation analyses with bootstrapping were used to test whether sleep quality mediated the relationship between TABP and CSVD. Results: Of the 764 participants [median age 65 (61-69) years, 59.9% female], the population with type A personality accounted for 44.8%. After adjusting for covariates, TABP scores (p = 0.03) and PSQI scores (p < 0.001) were significantly correlated with CSVD. In addition, sleep quality partially mediated the association between type A behavior and CSVD, and the mediating effect was 10.67%. Conclusion: This study showed that type A behavior was a risk factor for CSVD among older community-dwelling adults and that sleep quality mediated the relationship between type A behavior and CSVD. Changing type A behavior may help improve sleep quality, which may in turn reduce the prevalence of CSVD.

Current Knowledge about Headaches Attributed to Ischemic Stroke: Changes from Structure to Function.

Headaches are common after ischemic stroke (IS). Unlike primary headaches, headaches attributed to IS have specific clinical features. This review describes the epidemiology, clinical characteristics, risk factors, and influence of IS headaches. Previous reports were summarized to show the correlations between headaches and structural lesions in the cerebral cortex, subcortical white matter, deep gray matter nuclei, brainstem, and cerebellum. However, the substantial heterogeneity of IS, subjective evaluations of headaches, and inadequate cohort studies make it difficult to explore the pathophysiology of headaches attributed to IS. In our recommendation, favorable imaging techniques, such as magnetic resonance imaging and positron emission tomography, may provide new insights into mechanical studies of IS headaches from structure to function. It may also be helpful to extend the research field by targeting several shared signal transducers between headaches and IS. These markers might be neuropeptides, vasoactive substances, ion channels, or electrophysiologic changes.

NAD+ precursor nutritional supplements sensitize the brain to future ischemic events.

Nicotinamide adenine dinucleotide (NAD+) is a redox cofactor critical for oxidative phosphorylation. Nicotinamide (NAM) and nicotinamide riboside (NR) are NAD+ precursors widely used as nutritional supplements to augment oxidative phosphorylation. Indeed, NAD+ precursors have been reported to improve outcomes in ischemic stroke when administered as a rescue therapy after stroke onset. However, we have also reported that enhanced reliance on oxidative phosphorylation before ischemia onset might worsen outcomes. To address the paradox, we examined how NAD+ precursors modulate the outcome of middle cerebral artery occlusion in mice, when administered either 20 minutes after reperfusion or daily for three days before ischemia onset. A single post-ischemic dose of NAM or NR indeed improved tissue and neurologic outcomes examined at 72 hours. In contrast, pre-ischemic treatment for three days enlarged the infarcts and worsened neurological deficits. As a possible explanation for the diametric outcomes, a single dose of NAM or NR augmented tissue AMPK, PGC1α, SIRT1, and ATP in both naïve and ischemic brains, while the multiple-dose paradigm failed to do so. Our data suggest that NAD+ precursor supplements may sensitize the brain to subsequent ischemic events, despite their neuroprotective effect when administered after ischemia onset.

Regulatory T cells promote functional recovery after spinal cord injury by alleviating microglia inflammation via STAT3 inhibition.

BACKGROUND: Immediately after spinal trauma, immune cells, and proinflammatory cytokines infiltrate the spinal cord and disrupt the focal microenvironment, which impedes axon regeneration and functional recovery. Previous studies have reported that regulatory T cells (Tregs) enter the central nervous system and exert immunosuppressive effects on microglia during multiple sclerosis and stroke. However, whether and how Tregs interact with microglia and modulate injured microenvironments after spinal cord injury (SCI) remains unknown. METHOD: Regulatory T cells spatiotemporal characteristics were analyzed in a mouse contusion SCI model. Microglia activation status was evaluated by immunostaining and RNA sequencing. Cytokine production in injured spinal cord was examined using Luminex. The role of STAT3 in Treg-microglia crosstalk was investigated in a transwell system with isolated Tregs and primary microglia. RESULTS: Regulatory T cells infiltration of the spinal cord peaked on day 7 after SCI. Treg depletion promoted microglia switch to a proinflammatory phenotype. Inflammation-related genes, such as ApoD, as well as downstream cytokines IL-6 and TNF-α were upregulated in microglia in Treg-depleted mice. STAT3 inhibition was involved in Treg-microglia crosstalk, and STAT3 chemical blockade improved function recovery in Treg-depleted mice. CONCLUSION: Our results suggest that Tregs promote functional recovery after SCI by alleviating microglia inflammatory reaction via STAT3.

Effect of PCSK9 inhibition in combination with statin therapy on intracranial atherosclerotic stenosis: A high-resolution MRI study.

Introduction: Intracranial atherosclerotic stenosis (ICAS) is a common cause of stroke worldwide. Evolocumab, a proprotein convertase subtilisin/kexin type-9 inhibitor (PCSK9i), effectively lowers low-density lipoprotein (LDL) and produces favorable changes in coronary atherosclerosis. This study aimed to determine the effects of PCSK9i on intracranial plaques in moderate-intensity statin-treated individuals with ICAS. Methods: This prospective, observational study monitored the imaging and clinical outcomes of individuals with ICAS who were consecutively treated with moderate-intensity statins with or without PCSK9i. Individuals underwent monthly visits and repeat high-resolution MRI (HR-MRI) at week 12. The primary outcome was a change in HR-MRI after 12 weeks of treatment and the secondary outcome was major vascular events during follow-up. Results: Forty-nine individuals were studied (PCSK9i group: 26 individuals with 28 abnormal vascular regions; statin group: 23 with 27 regions). The PCSK9i group showed a significant reduction in the normalized wall index (0.83 vs. 0.86, p = 0.028) and stenosis degree (65.5 vs. 74.2%, p = 0.01). Similarly, a greater percentage of individuals with a good response to the efficacy of treatment were treated in the PCSK9i group than that in the statin group (75 vs. 44.4%, p = 0.021). The incidence of major vascular events was overall similar between the groups. The treatment options (OR = 8.441, p = 0.01) and prior diabetes (OR = 0.061, p = 0.001) were significantly associated with the efficacy of treatment. Discussion: Statin and PCSK9i combination treatment stabilized intracranial atherosclerotic plaques more often compared to statins alone, as documented by HR-MRI. Further study is warranted to determine if combination treatment improves clinical outcomes in ICAS.

Differences in Gray Matter Volume in Cerebral Small Vessel Disease Patients with and without Sleep Disturbance.

Recently, there has been increased interest in the relationship between cerebral small vessel disease (CSVD) and circadian rhythm disruption, particularly sleep disturbance. However, the neural mechanism of sleep disturbance in CSVD patients remains poorly understood. The purpose of this study is to explore the gray matter alterations in CSVD patients with and without sleep disturbance. 59 patients with CSVD and 40 healthy controls (HC) were recruited for the present study. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) questionnaire. CSVD patients were categorized into either the good sleepers group (CSVD-GS, n = 23) or the poor sleepers group (CSVD-PS, n = 36) based on PSQI score. Voxel-based morphometry (VBM) analysis was used to assess differences in gray matter volume (GMV) between groups. Multivariate regression analyses were performed to investigate the relationships between sleep quality, GMV, and white matter hyperintensities (WMH). We observed GMV differences between the three groups in the bilateral caudate, right thalamus, bilateral calcarine cortex, left precentral gyrus, right orbitofrontal cortex, left cingulate gyrus, and right sub-gyral temporal lobe. Additionally, the CSVD-PS group exhibited decreased GMV in the bilateral calcarine cortex yet increased GMV in the right caudate compared to the CSVD-GS group. In fully adjusted models, GMV of the right caudate and bilateral calcarine cortex was associated with sleep quality in CSVD patients. The present study revealed structural brain alterations in CSVD patients with sleep disturbance. These findings may provide novel insights into the neural mechanisms of sleep disturbance in CSVD.

Elevated Plasma Oligomeric Amyloid ß-42 Is Associated with Cognitive Impairments in Cerebral Small Vessel Disease.

Due to the heterogeneity of amyloid ß-42 (Aß42) species, the potential correlation between plasma oligomeric Aß42 (oAß42) and cognitive impairments in cerebral small vessel disease (CSVD) remains unclear. Herein, a sandwich ELISA for the specific detection of Aß42 oligomers (oAß42) and total Aß42 (tAß42) was developed based on sequence- and conformation-specific antibody pairs for the evaluation of plasma samples from a Chinese CSVD community cohort. After age and gender matching, 3-Tesla magnetic resonance imaging and multidimensional cognitive assessment were conducted in 134 CSVD patients and equal controls. The results showed that plasma tAß42 and oAß42 levels were significantly elevated in CSVD patients. By regression analysis, these elevations were correlated with the presence of CSVD and its imaging markers (i.e., white matter hyperintensities). Plasma Aß42 tests further strengthened the predictive power of vascular risk factors for the presence of CSVD. Relative to tAß42, oAß42 showed a closer correlation with memory domains evaluated by neuropsychological tests. In conclusion, this sensitive ELISA protocol facilitated the detection of plasma Aß42; Aß42, especially its oligomeric form, can serve as a biosensor for the presence of CSVD and associated cognitive impairments represented by memory domains.

Proteomics unite traditional toxicological assessment methods to evaluate the toxicity of iron oxide nanoparticles.

Iron oxide nanoparticles (IONPs) are the first generation of nanomaterials approved by the Food and Drug Administration for use as imaging agents and for the treatment of iron deficiency in chronic kidney disease. However, several IONPs-based imaging agents have been withdrawn because of toxic effects and the poor understanding of the underlying mechanisms. This study aimed to evaluate IONPs toxicity and to elucidate the underlying mechanism after intravenous administration in rats. Seven-week-old rats were intravenously administered IONPs at doses of 0, 10, 30, and 90 mg/kg body weight for 14 consecutive days. Toxicity and molecular perturbations were evaluated using traditional toxicological assessment methods and proteomics approaches, respectively. The administration of 90 mg/kg IONPs induced mild toxic effects, including abnormal clinical signs, lower body weight gain, changes in serum biochemical and hematological parameters, and increased organ coefficients in the spleen, liver, heart, and kidneys. Toxicokinetics, tissue distribution, histopathological, and transmission electron microscopy analyses revealed that the spleen was the primary organ for IONPs elimination from the systemic circulation and that the macrophage lysosomes were the main organelles of IONPs accumulation after intravenous administration. We identified 197 upregulated and 75 downregulated proteins in the spleen following IONPs administration by proteomics. Mechanically, the AKT/mTOR/TFEB signaling pathway facilitated autophagy and lysosomal activation in splenic macrophages. This is the first study to elucidate the mechanism of IONPs toxicity by combining proteomics with traditional methods for toxicity assessment.

Identification of a Signature for Predicting Prognosis and Immunotherapy Response in Patients with Glioma.

Glioma is a deadly tumor that accounts for the vast majority of brain tumors. Thus, it is important to elucidate the molecular pathogenesis and potential diagnostic and prognostic biomarkers of glioma. In the present study, gene expression profiles of GSE2223 were obtained from the Gene Expression Omnibus (GEO) database. Core modules and hub genes related to glioma were identified using weighted gene coexpression network analysis (WGCNA) and protein-protein interaction (PPI) network analysis of differentially expressed genes (DEGs). After a series of database screening tests, we identified 11 modules during glioma progression, followed by six hub genes (RAB3A, TYROBP, SYP, CAMK2A, VSIG4, and GABRA1) that can predict the prognosis of glioma and were validated in glioma tissues by qRT-PCR. The CIBERSORT algorithm was used to analyze the difference of immune cell infiltration between the glioma and control groups. Finally, Identification VSIG4 for immunotherapy response in patients with glioma demonstrating utility for immunotherapy research.

Abnormalities of retinal structure and microvasculature are associated with cerebral white matter hyperintensities.

BACKGROUND AND PURPOSE: Whilst retinal microvasculature represents cerebral small vessels, the retinal nerve fiber layer is the extended white matter of the brain. The aim was to investigate the correlation between changes in retina and white matter hyperintensities (WMHs). METHODS: Sixty-four candidates with WMHs received an optical coherence tomography angiography examination. WMHs were divided into mild or moderate/severe groups according to the Fazekas score. After imaging the superficial capillary plexus (SCP) and deep capillary plexus (DCP), the microvascular density parameters (vascular perfusion density [VPD], vascular length density [VLD] and fovea avascular zone area) and morphological parameters (vessel diameter index [VDI], fractal dimension [FD] and vessel tortuosity) were identified. A software algorithm measured the thickness of the peripapillary retina nerve fiber layer (PRNFL). RESULTS: Thirty-two were classified as having mild WMHs and 32 were moderate/severe. The median (interquartile range) ages of the two groups were 58 (54-64) and 61 (57-67) years, respectively. A decrease of FD, VPD and VLD in either SCP or DCP appeared with an increased risk of moderate/severe WMHs. Although changes of capillary plexus were not associated with paraventricular WMHs, decreased FD, VPD, VLD and fovea avascular zone area in either SCP or DCP were associated with an increased risk of moderate/severe deep WMHs (DWMHs). Participants with moderate/severe WMHs demonstrated reduced PRNFL thickness, particularly in the DWMHs, compared with mild WMHs. CONCLUSIONS: Abnormalities of retinal microvascular density, morphological parameters and PRNFL thickness are correlated with the incidence of moderate/severe WMHs, particularly the DWMHs, suggesting that arteriosclerosis and hypoperfusion are the causes of DWMHs.

Acute Treatment with Nicotinamide Riboside Chloride Reduces Hippocampal Damage and Preserves the Cognitive Function of Mice with Ischemic Injury.

Nicotinamide adenine dinucleotide (NAD) is a critical cosubstrate for enzymes involved in supplying energy to the brain. Nicotinamide riboside (NR), an NAD+ precursor, emerges as a neuroprotective factor after chronic brain insults. However, researchers have not determined whether it improves cognition after acute ischemia. In the present study, mice with middle cerebral artery occlusion were treated with NR chloride (NRC, 300 mg/kg, IP., 20 min after reperfusion). The results of the Morris water maze test revealed better recovery of learning and memory function in the NRC-treated group. Acute NRC treatment decreased hippocampal infarct volume, reduced neuronal loss and apoptosis in the hippocampus. Western blot and high-performance liquid chromatography assays of hippocampal tissues revealed that the activation of Sirtin-1 and adenosine 5' monophosphate-activated protein kinase was increased, the NAD content was elevated, and the production of adenosine triphosphate was strengthened by NRC. Collectively, acute NRC treatment increased the energy supply, reduced the neuronal loss and apoptosis, protected the hippocampus and ultimately promoted the recovery of cognitive function after brain ischemia.

Subxiphoid-subcostal thoracoscopic thymectomy for seropositive myasthenia offers equivalent remission rates and potentially faster recovery.

OBJECTIVES: To compare the perioperative and follow-up outcomes of patients with myasthenia gravis (MG) receiving subxiphoid-subcostal or unilateral thoracoscopic thymectomy and to identify the factors affecting MG prognosis. METHODS: From January 2013 to December 2019, a total of 137 consecutive MG patients received subxiphoid-subcostal thoracoscopic thymectomy (STT, n = 65) or conventional unilateral thoracoscopic thymectomy (UTT, n = 72). The primary outcomes of this study were perioperative complications, duration and expenses of hospitalization, VAS score and complete stable remission (CSR). RESULTS: The patients receiving STT had significantly shorter drainage duration and postoperative hospital stay and lower hospitalization expenses (P < 0.01). Pain scores on postoperative Days 1, 3, 7 and 14 were significantly lower in patients undergoing STT (P < 0.01). The average follow-up was 54.3 ± 24.18 months, with a CSR rate of 30.6% and an overall effective rate of 87.3%. Through uni- and multivariable analyses, shorter symptom duration and Myasthenia Gravis Foundation of America (MGFA) class I were independent predictors for CSR in MG patients receiving thymectomy. CONCLUSIONS: The present study not only showed that STT was a safe and feasible technique for MG, with a potentially faster postoperative recovery, lower hospitalization expenses, less postoperative pain and equivalent remission rate, but also revealed that shorter symptom duration and MGFA class I were favourable prognostic factors for CSR.

MiR196a-5p in extracellular vesicles released from human nasopharyngeal carcinoma enhance the phagocytosis and secretion of microglia by targeting ROCK1.

The microenvironment of the brain has become increasingly recognized as an essential regulator in metastatic and primary brain tumors. Recent studies demonstrate that circulating tumor-derived exosomes are critical for the brain tumor microenvironment. Nasopharyngeal carcinoma (NPC), a malignant tumor of the head and neck, often invades the skull base but infrequently extends to brain parenchyma. Neurobiological communication between microglia and tumor-derived extracellular vesicles (EVs) has been extensively studied, but how NPC cells regulate the immune microenvironment in the brain remains unknown. Here, we report that NPC derived EVs lead to increased microglial phagocytosis and proliferation, and heightened levels of IL-6, IL-8, CXCL1 and TGF-ß1. Analysis of microRNAs in EVs reveal that miR196a-5p is the major effector microRNA. Moreover, we demonstrate an enrichment of miR196a-5p in the plasmatic EVs of NPC patients. Further investigation demonstrated that miR196a-5p was transferred to microglia and regulated microglial structure and functions by downregulating the expression of ROCK1. Therefore, these data indicate that NPC-derived EVs are potent modulators of microglial functions in brain microenvironment. Regardless of brain colonization, EVs-mediated functional changes in microglia may be a universal phenomenon that results in the alteration of the tumor host's microenvironment in the brain.

Galectin-1 Contributes to Vascular Remodeling and Blood Flow Recovery After Cerebral Ischemia in Mice.

Galectin-1 is found in the vasculature and has been confirmed to promote angiogenesis in several cancer models. Furthermore, galectin-1 has been demonstrated to improve the recovery of cerebral ischemia. However, whether vascular remodeling contributes to this improvement is still unknown. In the present study, photochemical cerebral ischemia was induced in both galectin-1-treated (2 µg/day, i.c.v, 3 days) and galectin-1 knockout mice. Laser speckle imaging and immunofluorescent staining demonstrated that circulation and vascular remodeling in the ischemic cortex were improved by galectin-1 treatment but disrupted in galectin-1 knockout mice. Western blot analysis showed that the expression of matrix metallopeptidase-9 and vascular endothelial growth factor (VEGF) was regulated by galectin-1 in vivo. To determine how galectin-1 influences endothelial cells, the expression of galectin-1 in bEnd.3 cells was increased by transfection with an expression plasmid and knocked down by siRNA. As demonstrated by quantitative RT-PCR and western blot analysis, the expression of metallopeptidase-9, VEGF, and VEGF receptors was upregulated by galectin-1 overexpression but downregulated after galectin-1 knockdown. Flow cytometry, Transwell assay, and capillary-like tube formation assay were performed on cells after gene manipulation as well as cells treated by exogenous galectin-1 after anoxia. It demonstrated that galectin-1 potentiated the cell proliferation, migration capacity, and tube formation ability. Taken together, these data suggest that by targeting vascular remodeling, galectin-1 contributes to the restoration of blood flow, which promotes the recovery of mice after cerebral ischemic insults.

Thromboelastography predicts dual antiplatelet therapy-related hemorrhage in patients with acute ischemic stroke.

BACKGROUND: Stratification of the risk of hemorrhage in patients with acute ischemic stroke following dual antiplatelet therapy (DAPT) is challenging. It remains unclear whether thromboelastography (TEG) can be used to predict DAPT-related hemorrhagic events. OBJECTIVE: The present study aims to discover predictors for hemorrhage events after DAPT based on parameters such as TEG. METHODS: A total of 859 patients with acute ischemic stroke who received DAPT were recruited consecutively. Demographic, clinical, and neuroimaging characteristics were evaluated at baseline; TEG parameters were obtained 7 days later after DAPT. Hemorrhagic events were monitored about 1 month after the stroke. RESULTS: Of the patients, 61 (7.1%) had hemorrhagic events. Patients in the hemorrhage group had a lower adenosine diphosphate (ADP)-induced platelet-fibrin clot maximum amplitude and a higher ADP inhibition rate (ADP%) than those in the non-hemorrhage group (p<0.05). ADP% was confirmed as an independent predictor of hemorrhagic events with an optimal cut-off point of 83.3% (area under the curve (AUC) = 0.665, 95% CI 0.573 to 0.767, p<0.01). We constructed a logistic model based on D-dimer, National Institutes of Health Stroke Scale scores, and ADP% to predict hemorrhagic events in patients with acute ischemic stroke during DAPT (AUC=0.720, 95% CI 0.625 to 0.858, p<0.01), with a sensitivity of 72.1% and a specificity of 76.5%. CONCLUSIONS: Monitoring changes of TEG parameters helps to guide personalized DAPT for patients with ischemic stroke. A 30-82.3% range of ADP% is recommended for DAPT treatment.

Chemical characters and protective effect of Baqi Lingmao formula on experimental liver injury.

OBJECTIVE: To investigate the chemical characters of water-extract of Baqi Lingmao formula (BQLM formula) and its effects on anti-liver injury in model mice and live cells. METHODS: BQLM formula was composed of ten herbal medicines. We determined the contents of alkaloids, saponins, phenolic acids and flavonoid in BQLM formula by UV spectrophotometry. The active components of alkaloids and phenolic acids in BQLM formula were identified by HPLC chromatography. The anti-hepatic injury effects of BQLM formula were investigated with concanavalin A (ConA)-induced hepatitis model of mice, human liver LO2 and HepG2.2.15 cells. RESULTS: BQLM formula (2 and 10 g/kg, orally) significantly improved the damages of liver tissues and functions caused by ConA in mice, reduced the infiltration of inflammatory cells into liver and inhibited the inflammatory cytokine secretion of interferon-γ, tumor necrosis factor-α and interleukin-6. BQLM formula simultaneously decreased the levels of alanine aminotransferase and aspartate aminotransferase of liver and serum, and recovered the superoxide dismutase and catalase activities of liver to normal levels in ConA-induced hepatic-injury mice. The serum of BQLM formula group stimulated the human liver LO2 cell proliferation in vitro. Further, BQLM formula obviously promoted the proliferation of normal hepatocytes (LO2 cells) and inhibited the hepatocytes death induced by ConA. It also significantly inhibited the proliferation of HepG2.2.15 cells and decreased the secretion of HBsAg and HBeAg in vitro. CONCLUSIONS: BQLM formula has anti-inflammation and anti-hepatitis virus Beffects, and is capable of improving liver injury in vivo and in vitro.

Sleep Quality Mediates the Association Between Cerebral Small Vessel Disease Burden and Frailty: A Community-Based Study.

Background: Physical frailty is a common problem among older adults which usually leads to adverse health outcomes. The imaging markers of cerebral small vessel disease (CSVD) are associated with frailty, but the underlying mechanisms remain unclear. The present study aimed to investigate the mediating role of sleep quality in the relationship between CSVD burden and frailty. Methods: We performed a cross-sectional study and enrolled community residents. Frailty and sleep quality were measured using the Fried frailty phenotype and the Pittsburgh Sleep Quality Index (PSQI), respectively. A multivariate linear regression analysis and a Bootstrap analysis were performed to examine the association among the key variables and the mediating role of sleep quality. Results: Of the 726 participants (mean age: 65.5 ± 6.5 years, 59.8% female), the numbers (percentages) of the frail, prefrail, and robust residents were 49 (6.7%), 310 (42.7%), and 367 (50.6%), respectively. After adjusting for covariates, the CSVD burden and PSQI score were significantly associated with the frailty score. In addition, sleep quality played a partial mediating role in the association between CSVD burden and physical frailty. The mediating effect was 21.9%. Conclusion: The present study suggests that sleep quality is a mediator of this association between CSVD and frailty in community-dwelling older adults. Improving sleep quality might be helpful to mitigate the risk of frailty in CSVD patients.

Triglyceride glucose index influences platelet reactivity in acute ischemic stroke patients.

AIM: Insulin resistance was reported to increase the risk of ischemic stroke, which can be assessed by the triglyceride glucose (TyG) index. However, it remains unclear whether the TyG index influences the platelet reactivity during the treatment of ischemic patients. METHODS: Ischemic stroke patients receiving dual antiplatelet therapy (DAPT) within 48 h onset were consecutively included. The TyG index was calculated as ln (fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2). The top quartile of TyG index was defined as insulin resistance. The platelet reactivity was assessed by thromboelastography. The platelet inhibition rate induced by arachidonic acid (AA) or adenosine diphosphate (ADP) was used to confirm the high residual on-treatment platelet reactivity (HRPR) to aspirin or clopidogrel, respectively. The association between TyG index and platelet reactivity was assessed by Kruskal-Wallis test. The independent risk factors of HRPR were determined by multivariate logistic regression analysis. RESULTS: A total of 1002 patients were included and divided into 4 groups by quartiles of the TyG index (< 2.02; 2.02-2.27; 2.27-2.52; ≥2.52). The findings demonstrated that the maximum intensity of the clot increased, but the AA-induced platelet inhibition rate decreased, depending on the TyG index quartiles. No significant difference was found in the ADP-induced platelet inhibition rate among groups. The prevalence of aspirin HRPR increased depending on the TyG index quartile. Unlike the non-insulin resistance group, the insulin resistance group was independently associated with aspirin HRPR (OR = 1.689, 95% CI 1.14 to 2.51, P = 0.009). CONCLUSIONS: In acute ischemic stroke patients taking DAPT, the elevation of the TyG index is associated with enhanced platelet reactivity and higher prevalence of aspirin HRPR. Insulin resistance assessed by the TyG index could be an independent risk factor for aspirin HRPR.