Gastrodin Liposomes Block Crosstalk between Astrocytes and Glioma Cells via Downregulating Cx43 to Improve Antiglioblastoma Efficacy of Temozolomide.

The crosstalk between glioma cells and astrocytes plays a crucial role in developing temozolomide (TMZ) resistance of glioblastomas, together with the existence of the BBB contributing to the unsatisfactory clinical treatment of glioblastomas. Herein, we developed a borneol-modified and gastrodin-loaded liposome (Bo-Gas-LP), with the intent of enhancing the efficacy of TMZ therapy after intranasal administration. The results showed that Bo-Gas-LP improved GL261 cells' sensitivity to TMZ and prolonged survival of GL261-bearing mice by blocking the crosstalk between astrocytes and glioblastoma cells with the decrease of Cx43. Our study showed that intranasal Bo-Gas-LP targeting the crosstalk in glioblastoma microenvironments proposed a promising targeted therapy idea to overcome the current therapeutic limitations of TMZ-resistant glioblastomas.

Synthesis and biological evaluation of novel 1,2,3,4-tetrahydro-ß-carboline derivatives as potential antibacterial agents.

The quest for novel antibacterial agents is imperative in the face of escalating antibiotic resistance. Naturally occurring tetrahydro-ß-carboline (THßC) alkaloids have been highlighted due to their significant biological derivatives. However, these structures have been little explored for antibacterial drugs development. In this study, a series of 1,2,3,4-THßC derivatives were synthesized and assessed for their antibacterial prowess against both gram-positive and gram-negative bacteria. The compounds exhibited moderate to good antibacterial activity, with some compounds showing superior efficacy against gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA), to that of Gentamicin. Among these analogs, compound 3k emerged as a hit compound, demonstrating rapid bactericidal action and a significant post-antibacterial effect, with significant cytotoxicity towards human LO2 and HepG2 cells. In addition, compound 3k (10 mg/kg) showed comparable anti-MRSA efficacy to Ciprofloxacin (2 mg/kg) in a mouse model of abdominal infection. Overall, the present findings suggested that THßC derivatives based on the title compounds hold promising applications in the development of antibacterial drugs.

Process approach as a cognitive biomarker related to gray matter volume in mild cognitive impairment and Alzheimer's disease.

BACKGROUND: Process approach is valuable for memory assessment in Alzheimer's disease (AD) and mild cognitive impairment (MCI), yet its underlying mechanisms remain elusive. This study aims to synergize the process approach with brain structure analysis to explore both the discriminative capacity and potential mechanisms underlying the process approach. METHODS: 37 subjects of MCI, 35 subjects of AD and 38 subjects of healthy control (HC) were included. The process approach in Auditory Verbal Learning Test (AVLT), including discriminability (A'), response bias (B"D), semantic clustering (LBCsem) and serial clustering (LBCser) was performed. The gray matter volume (GMV) was analyzed by voxel-based morphometry. Receiver operating characteristic (ROC) analysis and partial correlations were conducted to explore the value of the process approach and investigate the relationship between the process approach, traditional indices of AVLT and GMV. RESULTS: ROC analysis showed the value of A', B"D and LBCser in differentiating MCI and AD. Combining AVLT-Immediately Recall (AVLT-IR) and LBCser showed a higher value in diagnosing MCI. Partial correlations revealed that in the MCI group, A' and B"D were mainly positively associated with GMV of the hippocampus and temporal lobe. CONCLUSION: This study indicated that the process approach is a promising cognitive biomarker to detect MCI and AD.

Apnea Testing Practice to Increase Baseline PaCO2 and Frequency of Blood Gas Analyses.

OBJECTIVE: To study the influence of the initial partial pressure of carbon dioxide (PaCO2) and frequency of blood gas analyses on the positivity rate and safety of apnea testing (AT). DESIGN: A prospective multicenter cohort study. SETTING: Seven teaching hospitals. PARTICIPANTS: A total of 55 patients who underwent AT. INTERVENTIONS: Patients were divided into 2 groups according to their initial PaCO2-the experimental group (≥40 mmHg, 27 patients) and the control group (<40 mmHg, 28 patients). Blood gas analysis was performed at 3, 5, and 8 minutes, and vital signs were taken. AT results and complications were compared between the groups. RESULTS: The initial PaCO2 of the experimental group was 42.8 ± 2.2 mmHg v 36.4 ± 2.9 mmHg in the controls. The AT positivity rate was 100%. The experimental group needed less time to reach the target PaCO2 than the control group (4.07 ± 1.27 minutes v 5.68 ± 2.06 minutes; p = 0.001). Twenty-six patients (96.3%) in the experimental group reached the target PaCO2 in 5 minutes v 17 in the control group (60.7%) (p = 0.001). Seven patients (12.7%) were unable to complete 8-minute disconnection due to hypotension. The experimental group had a slightly lower incidence of hypotension than the control group, but there was no statistical difference (7.4% v 17.9%, p = 0.245). CONCLUSION: Increasing the baseline PaCO2 and doing more blood gas analyses can significantly shorten the time needed for AT and improve the AT positivity rate.

New Clerodane Diterpenoids from Tinospora Capillipes with Antibacterial and Anti-Inflammatory Properties.

Four new clerodane diterpenoids, namely tinocapills A-D (1-4), and one known analogue (5) were isolated from the roots of Tinospora capillipes in the present study. The structures of these new compounds, including their absolute configurations, were determined through a combination of detailed spectroscopic analysis and theoretical statistical approaches, including electronic circular dichroism (ECD) analyses and quantum mechanical (QM)-NMR methods. Additionally, the stereostructure of 5 was confirmed via X-ray diffraction analysis. Furthermore, all these isolates were evaluated for their antibacterial and anti-inflammatory activities. Compounds 1, 2 and 5 demonstrated antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) with MICs ranging from 4-64 µg/mL, and compounds 3 and 4 exhibited potential anti-inflammatory effects by suppressing LPS-induced TNF-α and NO releases in RAW264.7 cells.

[Process Approach in Memory Assessment of Patients With Alzheimer's Disease and Mild Cognitive Impairment:A Review].

The process approach,a set of analytical methods used in neuropsychology,quantifies the word-list learning tests and conventional analytical methods and fully reflects the memory profile of the subject.Therefore,it is widely used in the memory assessment of patients with Alzheimer's disease(AD)and mild cognitive impairment(MCI).The common indices of process approach,such as learning slope,semantic clustering,serial position effects,discriminability,and response bias,are key components of memory assessment.This article reviews the application of common indices of process approach in memory assessment of AD and MCI patients and discusses the shortcomings and future research directions of process approach.

Co-occurrence of polyneuritis crainials and visual impairment: a case report and literature review.

BACKGROUND: Polyneuritis cranialis (PNC) with the disease characteristics of Guillain-Barré syndrome (GBS) in addition to both ocular and bulbar weakness in the absence of limb paralysis or ataxia is defined as an unusual variant of GBS. As evidence of central nervous system (CNS) involvement, visual impairment is an unusual finding complicating with GBS spectrum disorders and has never been reported in patients with PNC. METHODS: We describe a very rare case who clinically presented with progressive multiple cranial nerve palsy and visual impairment. Furthermore, a literature search of concurrent GBS and optic neuritis (ON) as well as PNC attributed to GBS was conducted. RESULTS: A diagnosis of PNC was considered due to the typical clinical characteristics as well as the presence of cerebrospinal fluid cytoalbumin dissociation and serum antibodies against gangliosides. The clinical manifestations and the bilateral optic nerve involvement in brain magnetic resonance imaging further suggested possible optic neuritis (ON). The patient received treatment with intravenous immunoglobulin followed by short-term use of corticosteroids and finally achieved a full recovery. Thirty-two previously reported cases (17 women, mean age 40) of concurrent GBS and ON and 20 cases of PNC (5 women, mean age 40) were analyzed. We further provided a comprehensive discussion on the potential etiologies, clinical features, therapeutic strategies, and prognosis. CONCLUSIONS: This rare case with the co-occurrence of PNC and visual impairment and the related literature review may help clinicians advance the understanding of GBS spectrum disorders and make appropriate diagnoses and treatment decisions for the rare variants and CNS complications of GBS.

Comparison of anesthetic effects of different doses of alfentanil combined with ciprofol in elderly patients undergoing ERCP: a randomized controlled trial.

BACKGROUND AND OBJECTS: Patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) are often old and poor in physical fitness. The purpose of this study was to investigate the anesthetic effect of different doses of alfentanil combined with ciprofol in elderly patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). METHODS: In this clinical trial, 137 patients, who were candidates for ERCP were randomly divided into three groups. Group A were given 0.15 µg/kg/min of alfentanil in maintenance stage, Group B were given 0.25 µg/kg/min and Group C were given 0.35 µg/kg/min. Mean arterial pressure (MAP), heart rate (HR), oxygen saturation (SpO2) of the patients at each time point including the entry into the operation room (T0), at the beginning of surgery(T1), 10 min after surgery(T2), 20 min after surgery(T3), 30 min after surgery(T4),endoscopy withdrawal (T5) were recorded. Adverse events(including respiratory depression, body movement and hypoxemia),the dosage of ciprofol, the time of operation time and awakening were recorded. RESULTS: Compared with Group A, MAP and HR in Group B and Group C was decreased during T1-T5 (P < 0.05). Compared with group B, MAP and HR in group C was decreased during T1-T5 (P < 0.05). Compared with Group A and Group C,the number of adverse reactions of Group B was decreased(P < 0.05). There was no statistical difference in surgical time among the three groups(P > 0.05),but a statistically significant difference in recovery time (P < 0.05). CONCLUSION: The adverse events of alfentanil 0.25µg/kg/min combined with ciprofol were low, and the anesthetic effect was the best.

[Changes in Plasma Amyloid-ß Level and Their Relationship With White Matter Microstructure in Patients With Mild Cognitive Impairment].

Objective To investigate the changes in plasma amyloid-ß (Aß) level and their relationship with white matter microstructure in the patients with amnesic mild cognitive impairment(aMCI) and vascular mild cognitive impairment (vMCI).Methods A total of 36 aMCI patients,20 vMCI patients,and 34 sex and age matched healthy controls (HC) in the outpatient and inpatient departments of the First Affiliated Hospital of Anhui Medical University were enrolled in this study.Neuropsychological scales,including the Mini-Mental State Examination,the Montreal Cognitive Assessment,and the Activity of Daily Living Scale,were employed to assess the participants.Plasma samples of all the participants were collected for the measurement of Aß42 and Aß40 levels.All the participants underwent magnetic resonance scanning to obtain diffusion tensor imaging (DTI) data.The DTI indexes of 48 white matter regions of each individual were measured (based on the ICBM-DTI-81 white-matter labels atlas developed by Johns Hopkins University),including fractional anisotropy (FA) and mean diffusivity (MD).The cognitive function,plasma Aß42,Aß40,and Aß42/40 levels,and DTI index were compared among the three groups.The correlations between the plasma Aß42/40 levels and DTI index of aMCI and vMCI patients were analyzed.Results The Mini-Mental State Examination and the Montreal Cognitive Assessment scores of aMCI and vMCI groups were lower than those of the HC group (all P<0.001).There was no significant difference in the Activity of Daily Living Scale score among the three groups (P=0.654).The plasma Aß42 level showed no significant difference among the three groups (P=0.227).The plasma Aß40 level in the vMCI group was higher than that in the HC group (P=0.014),while it showed no significant difference between aMCI and HC groups (P=1.000).The plasma Aß42/40 levels in aMCI and vMCI groups showed no significant differences from that in the HC group (P=1.000,P=0.105),while the plasma Aß42/40 level was lower in the vMCI group than in the aMCI group (P=0.016).The FA value of the left anterior limb of internal capsule in the vMCI group was lower than those in HC and aMCI groups (all P=0.001).The MD values of the left superior corona radiata,left external capsule,left cingulum (cingulate gyrus),and left superior fronto-occipital fasciculus in the vMCI group were higher than those in HC (P=0.024,P=0.001,P=0.003,P<0.001) and aMCI (P=0.015,P=0.004,P=0.019,P=0.001) groups,while the MD values of the right posterior limb of internal capsule (P=0.005,P=0.001) and left cingulum (hippocampus) (P=0.017,P=0.031) in the aMCI and vMCI groups were higher than those in the HC group.In the aMCI group,plasma Aß42/40 level was positively correlated with FA of left posterior limb of internal capsule (r=0.403,P=0.015) and negatively correlated with MD of the right fonix (r=-0.395,P=0.017).In the vMCI group,plasma Aß42/40 level was positively correlated with FA of the right superior cerebellar peduncle and the right anterior limb of internal capsule (r=0.575,P=0.008;r=0.639,P=0.002),while it was negatively correlated with MD of the right superior cerebellar peduncle and the right anterior limb of internal capsule (r=-0.558,P=0.011;r=-0.626,P=0.003).Conclusions Plasma Aß levels vary differently in the patients with aMCI and vMCI.The white matter regions of impaired microstructural integrity differ in the patients with different dementia types in the early stage.The plasma Aß levels in the patients with aMCI and vMCI are associated with the structural integrity of white matter,and there is regional specificity between them.

Submetric Spatial Resolution ROTDR Temperature Sensor Assisted by Wiener Deconvolution.

A submetric spatial resolution Raman optical time-domain reflectometry (ROTDR) temperature sensor assisted by the Wiener deconvolution postprocessing algorithm has been proposed and experimentally demonstrated. Without modifying the typical configuration of the ROTDR sensor and the adopted pump pulse width, the Wiener demodulation algorithm is able to recover temperature perturbations of a smaller spatial scale by deconvoluting the acquired Stokes and anti-Stokes signals. Numerical simulations have been conducted to analyze the spatial resolution achieved by the algorithm. Assisted by the algorithm, a typical ROTDR sensor adopting pump pulses of 20 ns width can realize the distributed temperature sensing with a spatial resolution of 0.5 m and temperature accuracy of 1.99 °C over a 2.1-km sensing fiber.

Changes of white matter integrity and structural network connectivity in nondemented cerebral small-vessel disease.

BACKGROUND: Previous studies have found widespread impairment of white matter (WM) integrity and disruption of structural network connectivity in cerebral small-vessel disease, but have not evaluated these changes jointly in nondemented patients. PURPOSE: To jointly investigate the microstructural impairment of WM and the related alterations of structural network topology in nondemented cerebral small-vessel disease (CSVD-ND). STUDY TYPE: Prospective. POPULATION: Thirty-seven CSVD-ND patients and 34 elderly controls, who were age-, sex-, and education-matched. FIELD STRENGTH/SEQUENCE: 3.0T/diffusion tensor imaging (DTI). ASSESSMENT: Clinical characteristics, lacunar infarct, and white matter hyperintensity (WMH) was assessed. A multiatlas likelihood fusion (MALF) algorithm was used for DTI-based brain segmentation and network node defining. Then the alterations of WM integrity and structural network topology were investigated jointly. STATISTICAL TESTS: Student's t-test, chi-square test, Mann-Whitney U-test, linear regression, Pearson correlation, and multiple comparison correction. RESULTS: Decreased fractional anisotropy and increased trace values were observed in predefined structures (P < 0.05, familywise error rate-corrected), including major commissural fibers, projection fibers, and some association fibers. Topologically, both groups showed small-worldness. CSVD-ND patients showed reduced global and local efficiency (P < 0.001). Despite widespread impairment of WM integrity, CSVD-ND patients only showed reduced nodal efficiency in the right superior occipital gyrus and the right lingual gyrus (P < 0.05, familywise error rate-corrected). The nodal local efficiency of the right precuneus was associated with the processing speed after adjusting the effect of lacunar infarct and WMH (r = -0.499, P = 0.038). DATA CONCLUSION: WM integrity was widely impaired in nondemented CSVD patients but structural network connectivity was relatively preserved. DTI may potentially provide information for the pathophysiology of CSVD in the nondemented phase. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:1162-1169.

Discovery of High-Performance Thermoelectric Chalcogenides through Reliable High-Throughput Material Screening.

High-throughput (HTP) material design is an emerging field and has been proved to be powerful in the prediction of novel functional materials. In this work, an HTP effort has been carried out for thermoelectric chalcogenides with diamond-like structures on the newly established Materials Informatics Platform (MIP). Specifically, the relaxation time is evaluated by a reliable yet efficient method, which greatly improves the accuracy of HTP electrical transport calculations. The results show that all the compounds may have power factors over 10 µW/cm·K2 if fully optimized. A new series of diamond-like chalcogenides with an atomic ratio of 1:2:4 possess relatively higher electrical transport properties among all the compounds investigated. One particular compound, CdIn2Te4, and its variations have been verified experimentally with a peak ZT over 1.0. Further analysis reveals the existence of general conductive networks and the similar Pisarenko relations under the same anion sublattice, and the transport distribution function is found to be a good indicator for the power factors for the compounds investigated. This work demonstrates a successful case study in HTP material screening.

Extensive basal ganglia hematomas treated by local thrombolysis versus conservative management - a comparative retrospective analysis.

OBJECTIVES: Single-target puncture plus catheter insertion into the clot is a routine step in hematoma aspiration and local thrombolysis for spontaneous intracerebral haemorrhage (ICH). However, multiple-target puncture of this procedure may imply faster hematoma reduction for large-area ICH. We retrospectively examined the outcomes after clot aspiration plus local thrombolysis with single-/double-target and conservative therapy for extensive basal ganglic hematomas. METHODS: A case note review was conducted on a consecutive series of ICH patients in a single centre with huge basal ganglia hematomas who underwent clots aspiration and thrombolysis or pure medical therapy. We analysed the clinical presentation, radiological features and treatment outcomes of ICH patients in single-target group, double-target group and conservative group. RESULTS: A total of 92 ICH cases were included in this study. At the post-treatment assessment, the average level by hematoma size in single-target and double-group was respectively smaller than that in the conservative group (20.61 ml vs. 15.75 ml vs 60.53 ml, p < 0.01). The 30-day case fatality rate in conservative group was respectively significantly higher than that in single-target and double-target groups (50% vs. 14.70% vs. 20.59%, p < 0.01). At the time of 6-month follow-up, the proportion of good survival in conservative group was respectively remarkably less than that in single- and double-target group (29.17% vs.64.71% vs. 67.65%, p < 0.01). But no difference was detected with respect to 30-day mortality or long-time outcome between the two micro-invasive groups (p = 0.53 and 0.798, respectively). CONCLUSION: Our data suggested for the massive basal ganglia hematomas, clot aspiration and thrombolysis can improve the short- and long-term prognosis compared with the pure conservative therapy. But, no evidence was found to demonstrate double-target of this procedure to be more effective than single-target to improve the outcome.

[Effect of Modified Dihuang Yinzi Recipe and Huatan Tongluo Decoction on Neurological Function of MCAO Rats].

Objective To observe the effect of Modified Dihuang Yinzi Recipe (MDYR) and Hua- tan Tongluo Decoction (HTD) on neurological function of middle cerebral artery occlusion (MCAO) model rats. Methods Forty SD rats were randomly divided into 5 groups, i.e., the sham-operation group, the model group, the nimodipine (NMDP) group, the MDYR group, and the HTD group, 8 in each group. NMDP liquid was administered to rats in the NMDP group by gastrogavage at the daily dose of 12 mg/kg. MDYR liquid was administered to rats in the MDYR group by gastrogavage at the daily dose of 7. 9 mg/kg. HTD liquid was administered to rats in the HTD group by gastrogavage at the daily dose of 6. 5 mg/kg. Equal volume of distilled water as administered to rats in the sham-operation group and the model group by gastrogavage. All intervention lasted for 7 successive days. MCAO rat model was established. The Zealonga neurology score was measured. Neurological function was scored at 3 and 6 h, day 1 , 6, and 7, respectively. Levels of corticotropin releasing hormone ( CRH) in plasma, adrenocorticotropic hormone (ACTH) and cortisone (CORT) in serum were detected using radioimmunoassay. The expression of ma- trix metalloproteinase-9 ( MMP9 ) in brain tissue was detected using immunohistochemical staining. Results Compared with the sham-operation group, the Zea-longa neurological score increased; levels of CRH and ACTH decreased (P <0. 05, P <0. 01) , expression levels of CORT and MMP-9 (in brain tis- sue) increased in the model group (P <0. 01). Compared with the model group, the Zea-longa neurologi- cal score obviously decreased, levels of CRH and ACTH increased, expression levels of CORT and MMP-9 (in brain tissue) decreased (P <0. 05, P <0. 01) in the MDYR group and the HTD group. Com- pared with the NMDP group, serum CORT decreased in the MDYR group (P <0. 05) ; MMP-9 expression level decreased in the HTD group (P <0. 01). Conclusions MDYR and HTD could obviously improve neurologic function of MCAO rats. Its mechanism might be related to MDYR regulating disordered HPA ax- is and HTD inhibiting MMP-9 expression.

No exacerbation of perihematomal edema with intraclot urokinase in patients with spontaneous intracerebral hemorrhage.

BACKGROUND: Perihematomal edema (PHE) can worsen patient outcomes after spontaneous intracerebral hemorrhage (ICH). Minimally invasive surgery (MIS) in combination with thrombolytic removal of hematoma has been proven to be a promising treatment strategy. However, preclinical studies have suggested that intraclot thrombolysis may exacerbate PHE after ICH. Herein, we investigated the effects of MIS and urokinase on PHE. METHODS: ICH patients were retrospectively identified from our institutional ICH database. Computerized volumetric analysis was applied to assess changes in both ICH and PHE volumes using computed tomographic (CT) scans of T1 (pre-MIS) and T2 (post-MIS) time points. Relative PHE (rPHE) was calculated as a ratio of PHE and T1 ICH volume. RESULTS: Data from 60 MIS plus urokinase (MIS + U), 20 MIS aspiration only (MO), and 30 control patients were analyzed. The ICH volume, PHE volume and rPHE on T2 CT in both MIS + U and MO groups significantly decreased as compared with the control group (ICH volume, 13.7 ± 5.7 ml, 17.0 ± 10.5 ml vs. 30.5 ± 10.3 ml, P < 0.01; PHE volume, 36.5 ± 18.9 ml, 32.2 ± 17.5 ml vs. 45.4 ± 16.0 ml, P < 0.01; rPHE, 0.9 ± 0.4, 0.8 ± 0.4 vs.1.4 ± 0.5, P < 0.01). Between the MIS + U and MO groups, the ICH volume, PHE volume and rPHE at T2 trended towards similarity, but was not significant (P = 0.09, P = 0.40, P = 0.43). Furthermore, we found a significant correlation between the percent of ICH removal and PHE reduction (r = 0.59, P < 0.01). There was no correlation between the cumulative dose of urokinase and either T2 PHE volume (r = 0.19; P = 0.16) or T2 rPHE (r = -0.12; P = 0.37). CONCLUSIONS: Hematoma evacuation using MIS leads to a significant reduction in PHE. Furthermore, the use of urokinase does not exacerbate PHE, making its hypothesized proedematous effects unlikely when the thrombolytic is administered directly into the clot.

Pneumocephalus following the minimally invasive hematoma aspiration and thrombolysis for ICH.

INTRODUCTION: The objective of this study was to clarify whether pneumocephalus occurred and affected the outcome following minimally invasive hematoma aspiration and thrombolysis for intracerebral hemorrhage (ICH). MATERIALS AND METHODS: A prospective case note review on all ICH patients treated with the micro-invasive procedure presenting to our division from 2006 to 2011 was conducted. Demographic, clinical, and outcome data were documented; head CT scans were applied postoperatively to identify the intracranial air collection. The ICH victims with pneumocephalus were included into Group A and the others into Group B. A multi-variant analysis was performed between Groups A and B to examine the effect of pneumocephalus on the prognosis. RESULTS: Data were collected on a total of 134 cases in this study, among whom 72.38% developed pneumocephalus postoperatively. No significant difference was demonstrated in terms of the preoperative and postoperative hematoma volume, Glasgow Coma Scale (GCS) score, middle line shift (MLS), and 30-day mortality rate between Groups A and B, respectively. Moreover, the long-term outcome rated by GCS of these two groups was also similar. Logistic regression analysis indicated double-needle puncture be an independent risk factor for both postoperative pneumocephalus (OR, 2.478; 95% CI, 1.010-6.080; P = 0.045) and its degree (OR, 11.84; 95%CI, 4.141-30.208; P < 0.001). CONCLUSION: The present study shows that pneumocephalus is common following the minimally invasive hematoma aspiration and thrombolysis for ICH but may not affect the outcome. And double-needle puncture may be the risk factor for pneumocephalus.

Intraclot recombinant tissue-type plasminogen activator reduces perihematomal edema and mortality in patients with spontaneous intracerebral hemorrhage.

The study aimed to investigate the impact of intraclot recombinant tissue-type plasminogen activator (rt-PA) on perihematomal edema (PHE) development in patients with intracerebral hemorrhage (ICH) treated with minimally invasive surgery (MIS) and the effects of intraclot rt-PA on the 30-day survival. We reviewed the medical records of ICH patients undergoing MIS between October 2011 and July 2013. A volumetric analysis was done to assess the change in PHE and ICH volumes at pre-MIS (T1), post-MIS (T2) and day 10-16 (T3) following diagnostic computed tomographic scans (T0). Forty-three patients aged 52.8±11.1 years with (n=30) or without rt-PA (n=13) were enrolled from our institutional ICH database. The median rt-PA dose was 1.5 (1) mg, with a maximum dose of 4.0 mg. The ratio of clot evacuation was significantly increased by intraclot rt-PA as compared with controls (77.9%±20.4% vs. 64%±15%; P=0.046). From T1 to T2, reduction in PHE volume was strongly associated with the percentage of clot evacuation (ρ=0.34; P=0.027). In addition, PHE volume was positively correlated with residual ICH volume at the same day (ρ ranging from 0.39-0.56, P<0.01). There was no correlation between the cumulative dose of rt-PA and early (T2) PHE volume (ρ=0.24; P=0.12) or delayed (T3) PHE volume (ρ=0.19; P=0.16). The 30-day mortality was zero in this cohort. In the selected cohort of ICH patients treated with MIS, intraclot rt-PA accelerated clot removal and had no effects on PHE formation. MIS aspiration and low dose of rt-PA seemed to be feasible to reduce the 30-day mortality in patients with severe ICH. A large, randomized study addressing dose titration and long-term outcome is needed.

[Effect of Yishen Daluo Decoction on the expression of PLP, Olig1, and Olig2 in mice with experimental autoimmune encephalomyelitis].

OBJECTIVE: To study the effect of Yishen Daluo Decoction (YDD) on the expression of protein lipoprotein (PLP), oligodendrocyte transcription factor 1 (Olig 1), and oligodendrocyte transcription factor 2 (Olig2) in mice with experimental autoimmune encephalomyelitis (EAE). METHODS: Totally 40 mice were randomly divided into 4 groups, i.e., the normal group, the model group, the Chinese medicine (CM) group, and the Western medicine (WM) group, 10 mice in each group. Each mouse in the model, CM, and WM groups was subcutaneously injected with 200 microL antigen emulsion (containing 150 micro g PLP139 -151 and 400 micro g H37RA) in two parts at the upper abdomen on the first day. 100 microLBordetella pertussis juice (containing 0. 6 x 10(6) Bordetella pertussis) was injected by caudal vein on the first and the third day. On the 7th day after modeling, each mouse in the normal group and the model group was intragastrically given normal saline (0. 1 mL/10 g). YDD (0. 2 g crude drug/10 g) was intragastrically given to mice in the CM group, and prednisone (0. 039 mg/10 g) was intragastrically given to mice in the WM group. All mice were intervened for 54 days. Changes of PLP, Olig1, and Olig2 in the brain tissue of EAE mice were detected by Western blot. Results The levels of PLP and Olig2 in the brain tissue of the model group were less than those of the normal group (P <0.05). Compared with the model group, the levels of PLP, Olig1, and Olig2 in the brain tissue increased in the CM group (P <0.05); the levels of PLP and Olig2 in the brain tissue increased in the WM group (P <0.05). Compared with the WM group, the level of Olig1 in the brain tissue increased in the CM group (P <0.05). CONCLUSION: YDD could enhance remyelination by elevating the levels of Olig1 and Olig2 in the brain tissue of EAE mice.

The altered functional status in vestibular migraine: A meta-analysis.

PURPOSE: Vestibular migraine (VM) is a disorder with prominent vestibular symptoms that are causally correlated with migraine and is the most prevalent neurological cause of episodic vertigo. Nevertheless, the functional underpinnings of VM remain largely unclear. This study aimed to reveal concordant alteration patterns of functional connectivity (FC) in VM patients. METHODS: We searched literature measuring resting-state FC abnormalities of VM patients in PubMed, Embase, Cochrane, and Scopus databases before May 2023. Furthermore, we applied the anisotropic effect size-signed differential mapping (AES-SDM) to conduct a whole-brain voxel-wise meta-analysis to identify the convergence of FC alterations in VM patients. RESULTS: Nine studies containing 251 VM patients and 257 healthy controls (HCs) were included. Relative to HCs, VM patients showed reduced activity in the left superior temporal gyrus and left midcingulate/paracingulate gyri, and increased activity in the precuneus, right superior parietal gyrus, and right middle frontal gyrus. Jackknife's analysis and subgroup analysis further supported the generalization and robustness of the main results. Furthermore, meta-regression analyses indicated that the Dizziness Handicap Inventory (DHI) ratings were positively correlated with the activity in the precuneus, while higher Headache Impact Test-6 and DHI scores were associated with lower activity within the left midcingulate/paracingulate gyri. CONCLUSIONS: The study indicates that VM is associated with specific functional deficits of VM patients in crucial regions involved in the vestibular and pain networks and provides further information on the pathophysiological mechanisms of VM.