Altered Resting-State Amygdalar Functional Connectivity in Primary Angle-Closure Glaucoma Patients.

BACKGROUND: Glaucoma patients frequently present with depressive symptoms, the development of which is closely associated with amygdalar activity. However, no studies to date have documented glaucoma-related changes in the functional connectivity (FC) of the amygdala. Accordingly, resting-state functional magnetic resonance imaging (rs-fMRI) analyses were herein used to evaluate changes in amygdalar FC in primary angle-closure glaucoma (PACG) patients. METHODS: In total, this study enrolled 36 PACG patients and 33 healthy controls (HCs). Complete eye exams were conducted for all PACG patients. After the preprocessing of magnetic resonance imaging (MRI) data, the bilateral amygdala was selected as a seed point, followed by the comparison of resting-state FC between the PACG and HC groups. Then, those brain regions exhibiting significant differences between these groups were identified, and relationships between the FC coefficient values for these regions and clinical variables of interest were assessed. RESULTS: These analyses revealed that as compared to HC individuals, PACG patients exhibited reductions in FC between the amygdala and the cerebellum_8, vermis_4_5, anterior central gyrus, supplementary motor area, paracentral lobule, putamen, middle frontal gyrus, and posterior cingulate gyrus, while enhanced FC was detected between the right and left amygdala. No significant correlations between these changes in amygdalar any any disease-related clinical parameters or disease duration were noted. CONCLUSIONS: Patients with PACG exhibit extensive resting state abnormalities with respect to the FC between the amygdala and other regions of the brain, suggesting that dysregulated amygdalar FC may play a role in the pathophysiology of PACG.

Toxicity evaluation of processing Evodiae fructus based on intestinal microbiota.

Background: With the development of healthcare services, drug efficacy, and safety have become the focus of drug use, and processing alters drug toxicity and efficacy, exploring the effects of processing on Evodiae fructus (EF) can guide the clinical use of drugs. Methods: Fifty male Kunming mice were randomly divided into the control group (CCN), raw small-flowered EF group (CRSEF), raw medium-flowered EF group (CRMEF), processing small-flowered EF group (CPSEF), and processing medium-flowered EF group (CPMEF). The CRSEF, CRMEF, CPSEF, and CPMEF groups were gavaged with aqueous extracts of raw small-flowered EF dry paste (RSEF), medium-flowered EF dry paste (RMEF), processing small-flowered EF dry paste (PSEF) and processing medium-flowered EF dry paste (PMEF), respectively, for 21 days at 5 times the pharmacopeial dosage. Upon concluding the experiment, histopathological sections of liver and kidney tissues were examined. Additionally, levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum creatinine (SCr), and blood urea nitrogen (BUN) were determined. DNA from the intestinal contents of the mice was extracted, and 16S rRNA full-length high-throughput sequencing was performed. Results: After fed EF 21 days, mice exhibited a decreasing trend in body weight. Comparative analysis with the CCN group revealed an upward trend in SCr, BUN, AST, and ALT levels in both CRSEF and CRMEF groups. The CRMEF group displayed notably elevated BUN and AST levels, with an observed increasing trend in Scr and ALT. Kidney sections unveiled cellular edema and considerable inflammatory cell infiltrates, whereas significant liver damage was not evident. Compared with CRSEF, Bun levels were significantly lower while AST levels were significantly higher in the CPMEF group. Additionally, the intestinal microbiota diversity and the relative abundance of Psychrobacter decreased significantly, and the relative abundance of Staphylococcus, Jeotgalicoccus, and Salinicoccus increased significantly in the CPMEF group. AST, ALT, and SCr were positively correlated with Staphylococcus, Jeotgalicoccus, and Salinicoccus. Conclusion: In conclusion, PMEF significantly increased harmful bacteria (Staphylococcus, Jeotgalicoccus, and Salinicoccu) and decreased beneficial bacteria. SEF with 5 times the clinical dose showed nephrotoxicity and SEF nephrotoxicity decreased after processing, but EF hepatotoxicity was not significant, which may be due to insufficient dose concentration and time.

Disrupted topological organization of functional brain networks in traumatic axonal injury.

Traumatic axonal injury (TAI) may result in the disruption of brain functional networks and is strongly associated with cognitive impairment. However, the neural mechanisms affecting the neurocognitive function after TAI remain to be elucidated. We collected the resting-state functional magnetic resonance imaging data from 28 patients with TAI and 28 matched healthy controls. An automated anatomical labeling atlas was used to construct a functional brain connectome. We utilized a graph theoretical approach to investigate the alterations in global and regional network topologies, and network-based statistics analysis was utilized to localize the connected networks more precisely. The current study revealed that patients with TAI and healthy controls both showed a typical small-world topology of the functional brain networks. However, patients with TAI exhibited a significantly lower local efficiency compared to healthy controls, whereas no significant difference emerged in other small-world properties (Cp, Lp, γ, λ, and σ) and global efficiency. Moreover, patients with TAI exhibited aberrant nodal centralities in some regions, including the frontal lobes, parietal lobes, caudate nucleus, and cerebellum bilaterally, and right olfactory cortex. The network-based statistics results showed alterations in the long-distance functional connections in the subnetwork in patients with TAI, involving these brain regions with significantly altered nodal centralities. These alterations suggest that brain networks of individuals with TAI present aberrant topological attributes that are associated with cognitive impairment, which could be potential biomarkers for predicting cognitive dysfunction and help understanding the neuropathological mechanisms in patients with TAI.

Construction and validation of a risk prediction model for acute kidney injury in patients after cardiac arrest.

OBJECTIVE: Identifying patients at high risk for cardiac arrest-associated acute kidney injury (CA-AKI) helps in early preventive interventions. This study aimed to establish and validate a high-risk nomogram for CA-AKI. METHODS: In this retrospective dataset, 339 patients after cardiac arrest (CA) were enrolled and randomized into a training or testing dataset. The Student's t-test, non-parametric Mann-Whitney U test, or χ2 test was used to compare differences between the two groups. Optimal predictors of CA-AKI were determined using the Least Absolute Shrinkage and Selection Operator (LASSO). A nomogram was developed to predict the early onset of CA-AKI. The performance of the nomogram was assessed using metrics such as area under the curve (AUC), calibration curves, decision curve analysis (DCA), and clinical impact curve (CIC). RESULTS: In total, 150 patients (44.2%) were diagnosed with CA-AKI. Four independent risk predictors were identified and integrated into the nomogram: chronic kidney disease, albumin level, shock, and heart rate. Receiver operating characteristic (ROC) analyses showed that the nomogram had a good discrimination performance for CA-AKI in the training dataset 0.774 (95%CI, 0.715-0.833) and testing dataset 0.763 (95%CI, 0.670-0.856). The AUC values for the two groups were calculated and compared using the Hanley-McNeil test. No statistically significant differences were observed between the groups. The calibration curve demonstrated good agreement between the predicted outcome and actual observations. Good clinical usefulness was identified using DCA and CIC. CONCLUSION: An easy-to-use nomogram for predicting CA-AKI was established and validated, and the prediction efficiency of the clinical model has reasonable clinical practicability.

Sex differences of the triple network model in children with autism: A resting-state fMRI investigation of effective connectivity.

Autism spectrum disorder (ASD) has a pronounced male predominance, but the underlying neurobiological basis of this sex bias remains unclear. Gender incoherence (GI) theory suggests that ASD is more neurally androgynous than same-sex controls. Given its central role, altered structures and functions, and sex-dependent network differences in ASD, the triple network model, including the central executive network (CEN), default mode network (DMN), and salience network (SN), has emerged as a candidate for characterizing this sex difference. Here, we measured the sex-related effective connectivity (EC) differences within and between these three networks in 72 children with ASD (36 females, 8-14 years) and 72 typically developing controls (TCs) (36 females, 8-14 years) from 5 sites of the Autism Brain Imaging Data Exchange repositories using a 2 × 2 analysis of covariance factorial design. We also assessed brain-behavior relationships and the effects of age on EC. We found significant diagnosis-by-sex interactions on EC: females with ASD had significantly higher EC than their male counterparts within the DMN and between the SN and CEN. The interaction pattern supported the GI theory by showing that the higher EC observed in females with ASD reflected a shift towards the higher level of EC displayed in male TCs (neural masculinization), and the lower EC seen in males with ASD reflected a shift towards the lower level of EC displayed in female TCs (neural feminization). We also found significant brain-behavior correlations and significant effects of age on EC.

[Predictive value of sequential organ failure assessment on 28-day mortality in patients with post-cardiac arrest syndrome].

OBJECTIVE: To evaluate the predictive value of sequential organ failure assessment (SOFA) for 28-day mortality in patients with post-cardiac arrest syndrome (PCAS). METHODS: Retrospective analysis of 125 patients with PCAS who were treated in Emergency Intensive Care Unit (EICU) of Wenzhou People's Hospital from July 2016 to July 2021. Clinical data were collected, including age, gender, underlying diseases, acute physiology and chronic health evaluation II (APACHE II), SOFA score on admission to EICU and 28-day mortality. Univariate and multivariate Logistic regression model was constructed to analyze the influencing factors of PCAS patients, which was used to examine the independent correlation between SOFA score and 28-day mortality. Receiver operator characteristic curve (ROC curve) was used to determine the best predictive value of SOFA score and 28-day mortality in PCAS patients. RESULTS: Among the 125 PCAS patients, there were 91 males and 34 females with an average age of (58.7±15.1) years old, and 97 died and 28 survived within 28 days. The overall SOFA score ranged from 7 to 15 points, with an average of 10.9 (10.0, 12.0) points. The SOFA score of non-survival group was significantly higher than that of the survival group [points: 11.0 (10.0, 12.0) vs. 9.5 (9.0, 10.0), P < 0.05]. This difference between SOFA score mainly caused by the neurological and cardiovascular systems. After excluding neurological factors, the SOFA score of the non-survival group was still significantly higher than that of the survival group [points: 8.0 (6.0, 8.0) vs. 6.5 (6.0, 7.0), P < 0.05]. SOFA score was found to be an independent risk factor for 28-day mortality in PCAS patients by multifactorial Logistic regression analysis [odds ratio (OR) = 1.97, 95% confidence interval (95%CI) was 1.24-3.04]. The correlation between neurological score and mortality was the highest in subgroups (OR = 3.47, 95%CI was 1.04-11.52). The area under the ROC curve (AUC) predicted by SOFA score was 0.81 (95%CI was 0.73-0.89). When SOFA score cut-off value was 10.5 points (10 or 11 points), the sensitivity and specificity of SOFA score for predicting 28-day mortality in patients with PCAS were 67.0% and 82.1%, respectively. CONCLUSIONS: The SOFA score is quite accurate in predicting 28-day mortality in patients with PCAS.

Relationship between serum lactate dehydrogenase and mortality after cardiac arrest: A retrospective cohort study.

Serum lactate dehydrogenase (LDH) has been identified as an independent risk factor for predicting all-cause mortality in patients with multiple diseases. However, the prognostic value of LDH levels in post-cardiac arrest patients remains uncertain. This study aimed to assess the association between LDH and mortality in intensive care unit (ICU) patients after cardiac arrest. This retrospective observational study is based on data from the Dryad Digital Repository, which included 374 consecutive adult patients after cardiac arrest. Patients were divided into 2 groups based on median LDH values. A multivariate Cox proportional hazards model was established to assess the independent relationship between LDH and ICU mortality. Cumulative mortality was compared using Kaplan-Meier curves. The cohort included 374 patients, of which 51.9% (194/374) died in the ICU. The overall death rate from cardiac arrest was significantly higher for patients with LDH ≥ 335 IU/L (59.6%) than for those with LDH < 335 IU/L (44.1%). In multiple Cox regression models, hazard ratios (HR) and corresponding 95% confidence intervals (CI) for logLDH and the 2 LDH groups were 1.72 (1.07, 2.78) and 1.42 (1.04, 1.93), respectively. Participants with LDH ≥ 335IU/L had a higher incidence of ICU mortality than LDH < 335 IU/L, as shown by the Kaplan-Meier curves (P = .0085). Subgroup analysis revealed that the association between LDH and ICU mortality was vitally stable, with all P interactions from different subgroups >.05. Serum LDH levels are positively associated with ICU mortality in patients after cardiac arrest, especially for patients with LDH ≥ 335 IU/L.

River Ecosystem Health Assessment Using a Combination Weighting Method: A Case Study of Beijing Section of Yongding River in China.

(1) Background: River health assessment provides the foundation for sustainable river development and management. However, existing assessments have no uniform standards and methods. (2) Methods: The combination weighting method was proposed, drawing on the advantages of subjective and objective weighting methods. To comprehensively investigate the river health level, an index system based on 16 indices selected from river morphology, river water environment, riparian condition, and social services level was established. The method and framework were applied to the Beijing section of Yongding River in China. (3) Results: The comprehensive weights of river morphology, river water environment, riparian condition, and social services are 0.1614, 0.3170, 0.4459, and 0.0757, respectively. The river health comprehensive index of Yongding River is 3.805; the percentages of excellent, healthy, sub-healthy, unhealthy, and sick river segments are 0%, 11%, 69%, 20%, and 0%, respectively. (4) Conclusions: The results indicate that Yongding River is in a sub-healthy state, and the riparian condition is the key factor that affects the river ecosystem health. Health level exhibited a remarkable spatial variation, mainly influenced by anthropogenic activities, and effective measures are needed to minimize the impact in fragile ecological areas.

Altered functional connectivity of the thalamus in primary angle-closure glaucoma patients: A resting-state fMRI study.

Background and objectives: Glaucoma is one of the leading irreversible causes of blindness worldwide, and previous studies have shown that there is abnormal functional connectivity (FC) in the visual cortex of glaucoma patients. The thalamus is a relay nucleus for visual signals; however, it is not yet clear how the FC of the thalamus is altered in glaucoma. This study investigated the alterations in thalamic FC in patients with primary angle-closure glaucoma (PACG) by using resting-state functional MRI (rs-fMRI). We hypothesized that PACG patients have abnormal FC between the thalamus and visual as well as extravisual brain regions. Methods: Clinically confirmed PACG patients and age- and gender-matched healthy controls (HCs) were evaluated by T1 anatomical and functional MRI on a 3 T scanner. Thirty-four PACG patients and 33 HCs were included in the rs-fMRI analysis. All PACG patients underwent complete ophthalmological examinations; included retinal nerve fiber layer thickness (RNFLT), intraocular pressure (IOP), average cup-to-disc ratio (A-C/D), and vertical cup-to-disc ratio (V-C/D). After the MRI data were preprocessed, the bilateral thalamus was chosen as the seed point; and the differences in resting-state FC between groups were evaluated. The brain regions that significantly differed between PACG patients and HCs were identified, and the correlations were then evaluated between the FC coefficients of these regions and clinical variables. Results: Compared with the HCs, the PACG patients showed decreased FC between the bilateral thalamus and right transverse temporal gyrus, between the bilateral thalamus and left anterior cingulate cortex, and between the left thalamus and left insula. Concurrently, increased FC was found between the bilateral thalamus and left superior frontal gyrus in PACG patients. The FC between the bilateral thalamus and left superior frontal gyrus was positively correlated with RNFLT and negatively correlated with the A-C/D and V-C/D. The FC between the left thalamus and left insula was negatively correlated with IOP. Conclusion: Extensive abnormal resting-state functional connections between the thalamus and visual and extravisual brain areas were found in PACG patients, and there were certain correlations with clinical variables, suggesting that abnormal thalamic FC plays an important role in the progression of PACG.

Is Brain Network Efficiency Reduced in Young Survivors of Acute Lymphoblastic Leukemia?-Evidence from Individual-Based Morphological Brain Network Analysis.

Altered cerebral structure and function have been observed in young survivors of acute lymphoblastic leukemia (ALL). However, the topological organization of the morphological brain networks (MBNs) has not yet been investigated at the individual level. Twenty-three young survivors of ALL and twenty healthy controls (HCs) were recruited and underwent T1-weighted magnetic resonance imaging (MRI) scanning. After preprocessing and segmentation, individual-based MBNs were constructed based on the morphological similarity of gray matter using the combined Euclidean distance. Young survivors showed a significantly lower global clustering coefficient (p = 0.008) and local efficiency (p = 0.035) compared with HCs. In addition, ALL survivors exhibited bidirectional alterations (decreases and increases) in nodal centrality and efficiency around the Rolandic operculum and posterior occipital lobe (p < 0.05, false discovery rate (FDR) corrected). Altered nodal topological efficiencies were associated with off-therapy duration and verbal memory capacity in the digit span test (p < 0.05, FDR corrected). Network-based statistical analysis revealed decreased morphological connections mainly in the pallidum subnetwork, which was negatively correlated with off-therapy durations (p < 0.05). Overall, the topological organization of the individual-based MBNs was disrupted in the young survivors of ALL, which may play a crucial role in executive efficiency deficits.

Efficacy and safety of ubrogepant for migraine: a meta-analysis of randomized controlled studies.

Introduction: The efficacy of ubrogepant 50 mg versus 100 mg daily for migraine remained controversial. We conducted a systematic review and meta-analysis to compare the efficacy and safety of ubrogepant 50 mg versus 100 mg daily on treatment in migraine patients.Methods: We have searched PubMed, EMbase, Web of science, EBSCO, Cochrane library databases and SCOPUS through 21 March 2022 for randomized controlled trials (RCTs) assessing the effect of ubrogepant 50 mg versus 100 mg on treatment efficacy in migraine patients. This meta-analysis was performed using the random-effect model.Results: Three RCTs were included in the meta-analysis. Overall, compared with ubrogepant 100 mg in migraine patients, ubrogepant 50 mg obtained comparable pain freedom at 2 h (OR = 0.86; 95% CI = 0.64-1.15; p = 0.310), sustained pain freedom 2-24 h (OR = 0.76; 95% CI = 0.54-1.07; p = 0.110), photophobia absence at 2 h (OR = 0.80; 95% CI = 0.63-1.02; p = 0.070), phonophobia absence at 2 h (OR = 1.07; 95% CI = 0.82-1.40; p = 0.620) and nausea absence at 2 h (OR = 1.02; 95% CI = 0.79-1.32; p = 0.880). In terms of safety, adverse events were found to be increased in ubrogepant 100 mg as compared to ubrogepant 50 mg (OR = 0.81; 95% CI = 0.67-0.99; p = 0.040), and there was no statistical difference of serious adverse events between two groups (OR = 0.87; 95% CI = 0.40-1.91; p = 0.720).Conclusions: Ubrogepant 50 mg and 100 mg may be equally effective to alleviate migraine, but ubrogepant 100 mg led to increase incidence of adverse events.

Suboptimal states and frontoparietal network-centered incomplete compensation revealed by dynamic functional network connectivity in patients with post-stroke cognitive impairment.

Background: Neural reorganization occurs after a stroke, and dynamic functional network connectivity (dFNC) pattern is associated with cognition. We hypothesized that dFNC alterations resulted from neural reorganization in post-stroke cognitive impairment (PSCI) patients, and specific dFNC patterns characterized different pathological types of PSCI. Methods: Resting-state fMRI data were collected from 16 PSCI patients with hemorrhagic stroke (hPSCI group), 21 PSCI patients with ischemic stroke (iPSCI group), and 21 healthy controls (HC). We performed the dFNC analysis for the dynamic connectivity states, together with their topological and temporal features. Results: We identified 10 resting-state networks (RSNs), and the dFNCs could be clustered into four reoccurring states (modular, regional, sparse, and strong). Compared with HC, the hPSCI and iPSCI patients showed lower standard deviation (SD) and coefficient of variation (CV) in the regional and modular states, respectively (p < 0.05). Reduced connectivities within the primary network (visual, auditory, and sensorimotor networks) and between the primary and high-order cognitive control domains were observed (p < 0.01). Conclusion: The transition trend to suboptimal states may play a compensatory role in patients with PSCI through redundancy networks. The reduced exploratory capacity (SD and CV) in different suboptimal states characterized cognitive impairment and pathological types of PSCI. The functional disconnection between the primary and high-order cognitive control network and the frontoparietal network centered (FPN-centered) incomplete compensation may be the pathological mechanism of PSCI. These results emphasize the flexibility of neural reorganization during self-repair.

Using Fractional Amplitude of Low-Frequency Fluctuations and Functional Connectivity in Patients With Post-stroke Cognitive Impairment for a Simulated Stimulation Program.

Stroke causes alterations in local spontaneous neuronal activity and related networks functional connectivity. We hypothesized that these changes occur in patients with post-stroke cognitive impairment (PSCI). Fractional amplitude of low-frequency fluctuations (fALFF) was calculated in 36 patients with cognitive impairment, including 16 patients with hemorrhagic stroke (hPSCI group), 20 patients with ischemic stroke (iPSCI group). Twenty healthy volunteers closely matched to the patient groups with respect to age and gender were selected as the healthy control group (HC group). Regions with significant alteration were regarded as regions of interest (ROIs) using the one-way analysis of variance, and then the seed-based functional connectivity (FC) with other regions in the brain was analyzed. Pearson correlation analyses were performed to investigate the correlation between functional indexes and cognitive performance in patients with PSCI. Our results showed that fALFF values of bilateral posterior cingulate cortex (PCC)/precuneus and bilateral anterior cingulate cortex in the hPSCI group were lower than those in the HC group. Compared with the HC group, fALFF values were lower in the superior frontal gyrus and basal ganglia in the iPSCI group. Correlation analysis showed that the fALFF value of left PCC was positively correlated with MMSE scores and MoCA scores in hPSCI. Besides, the reduction of seed-based FC values was reported, especially in regions of the default-mode network (DMN) and the salience network (SN). Abnormalities of spontaneous brain activity and functional connectivity are observed in PSCI patients. The decreased fALFF and FC values in DMN of patients with hemorrhagic and SN of patients with ischemic stroke may be the pathological mechanism of cognitive impairment. Besides, we showed how to use fALFF values and functional connectivity maps to specify a target map on the cortical surface for repetitive transcranial magnetic stimulation (rTMS).

The Efficacy of Memantine for the Treatment of Migraine: A Meta-Analysis of Randomized Controlled Studies.

INTRODUCTION: The efficacy of memantine for migraine remains controversial. We conduct a systematic review and meta-analysis to explore the influence of memantine versus placebo on treatment in migraine patients. METHODS: We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through February 2020 for randomized controlled trials assessing the effect of memantine versus placebo on treatment efficacy in migraine patients. This meta-analysis is performed using the random-effect model. RESULTS: Three randomized controlled trials are included in the meta-analysis. Overall, compared with control group in migraine patients, memantine treatment is associated with substantially reduced monthly attack frequency (mean difference [MD], -2.14; 95% confidence interval [CI], -2.83 to -1.46; P < 0.00001), number of migraine days (MD, -4.17; 95% CI, -6.40 to -1.93; P = 0.0003) and Migraine Disability Assessment (MD, -5.63; 95% CI, -6.46 to -4.79; P < 0.00001), but demonstrates no obvious influence on acute pain medications (MD, -1.23; 95% CI, -4.63 to 2.17; P = 0.48). CONCLUSIONS: Memantine treatment may benefit to the control of migraine.

Gensenoside Rg1 protects against lipopolysaccharide- and d-galactose-induced acute liver failure via suppressing HMGB1-mediated TLR4-NF-κB pathway.

AIM: Acute liver failure (ALF) is a life-threatening acute liver injury (ALI) with high mortality. Gensenoside Rg1 (G-Rg1) effects on Lipopolysaccharide- (LPS-) and d-galactose-(D-gal-) induced ALI, but its effects on ALF remained unclear. This paper aimed to validate its possible efficacy on ALF prevention. METHODS: For in vivo studies, histological examination was performed using hematoxylin-eosin (H&E) staining, and alanine aminotransferase (ALT), aspartate aminotransminase (AST), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) contents were measured. Levels of inflammatory cytokines tumor necrosis factor-α (TNF-α) and Interleukin-6 (IL-6) were quantified via enzyme-linked immunosorbent assay (ELISA). Human bronchial epithelial cell line BEAS-2B was used for ALF model in vitro and its viability was measured by MTT assay. Expressions of high mobility group box 1 (HMGB1) and toll-like receptor 4-Nuclear Factor-κB (TLR4-NF-κB) pathway-related proteins were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot as needed. RESULTS: G-Rg1 relieved LPS- and D-gal-induced hepatic injury, and reduced ALT, AST and MDA levels but upregulated SOD and GSH levels, with downregulation on TNF-α and IL-6 levels. Expressions of HMGB1, TLR4 and NF-κB pathway-related proteins were also down-regulated after G-Rg1 treatment both in vivo and in vitro, while BEAS-2B cell viability was increased. However, overexpressed HMGB1 reversed the effects of G-Rg1 treatment in vitro. CONCLUSION: G-Rg1 had a protective effect against LPS- and D-gal-induced ALF both in vitro and in vivo, which might be related to inhibited HMGB1-mediated TLR4-NF-κB Pathway. These discoveries suggested that G-Rg1 could be a potential agent for prevention against ALF.

Altered Effective Connectivity Measured by Resting-State Functional Magnetic Resonance Imaging in Posterior Parietal-Frontal-Striatum Circuit in Patients With Disorder of Consciousness.

OBJECTIVE: Disorder of consciousness (DoC) resulting from severe brain injury is characterized by cortical and subcortical dysconnectivity. However, research on seed-based effective connectivity (EC) of DoC might be questioned as to the heterogeneity of prior assumptions. METHODS: Functional MRI data of 16 DoC patients and 16 demographically matched healthy individuals were analyzed. Revised coma recovery scale (CRS-R) scores of patients were acquired. Seed-based d mapping permutation of subject images (SDM-PSI) of meta-analysis was performed to quantitatively synthesize results from neuroimaging studies that evaluated resting-state functional activity in DoC patients. Spectral dynamic causal modeling (spDCM) was used to assess how EC altered between brain regions in DoC patients compared to healthy individuals. RESULTS: We found increased effective connectivity in left striatum and decreased effective connectivity in bilateral precuneus (preCUN)/posterior cingulate cortex (PCC), bilateral midcingulate cortex and left middle frontal gyrus in DoC compared with the healthy controls. The resulting pattern of interaction in DoC indicated disrupted connection and disturbance of posterior parietal-frontal-striatum, and reduced self-inhibition of preCUN/PCC. The strength of self-inhibition of preCUN/PCC was negatively correlated with the total score of CRS-R. CONCLUSION: This impaired EC in DoC may underlie disruption in the posterior parietal-frontal-striatum circuit, particularly damage to the cortico-striatal connection and possible loss of preCUN/PCC function as the main regulatory hub.

Decreased Functional Connectivities of Low-Degree Level Rich Club Organization and Caudate in Post-stroke Cognitive Impairment Based on Resting-State fMRI and Radiomics Features.

BACKGROUND: Stroke is an important cause of cognitive impairment. Rich club organization, a highly interconnected network brain core region, is closely related to cognition. We hypothesized that the disturbance of rich club organization exists in patients with post-stroke cognitive impairment (PSCI). METHODS: We collected data on resting-state functional magnetic resonance imaging (rs-fMRI) with 21 healthy controls (HC), 16 hemorrhagic stroke (hPSCI), and 21 infarct stroke (iPSCI). 3D shape features and first-order statistics of stroke lesions were extracted using 3D slicer software. Additionally, we assessed cognitive function using the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). RESULTS: Normalized rich club coefficients were higher in hPSCI and iPSCI than HC at low-degree k-levels (k = 1-8 in iPSCI, k = 2-8 in hPSCI). Feeder and local connections were significantly decreased in PSCI patients versus HC, mainly distributed in salience network (SN), default-mode network (DMN), cerebellum network (CN), and orbitofrontal cortex (ORB), especially involving the right and left caudate with changed nodal efficiency. The feeder and local connections of significantly between-group difference were positively related to MMSE and MoCA scores, primarily distributed in the sensorimotor network (SMN) and visual network (VN) in hPSCI, SN, and DMN in iPSCI. Additionally, decreased local connections and low-degree ϕnorm(k) were correlated to 3D shape features and first-order statistics of stroke lesions. CONCLUSION: This study reveals the disrupted low-degree level rich club organization and relatively preserved functional core network in PSCI patients. Decreased feeder and local connections in cognition-related networks (DMN, SN, CN, and ORB), particularly involving the caudate nucleus, may offer insight into pathological mechanism of PSCI patients. The shape and signal features of stroke lesions may provide an essential clue for the damage of functional connectivity and the whole brain networks.

Altered Functional Connectivity Density in Young Survivors of Acute Lymphoblastic Leukemia Using Resting-State fMRI.

OBJECTIVE: Using functional connectivity density (FCD) mapping measured by resting-state functional magnetic resonance imaging (rs-fMRI), an ultrafast data-driven graph theory approach, we attempted to study the abnormalities in neural activity of young survivors of acute lymphoblastic leukemia (ALL) and to explore the neuropathological evidence of chemotherapy-related cognitive impairment of patients. METHODS: Twenty young survivors of ALL and 18 well-matched healthy controls (HCs) were recruited in this study. All ALL patients and healthy controls underwent rs-fMRI scans and completed neurocognitive testing. The between-group differences in short-range and long-range FCD were calculated by the option of degree centrality (DC) in MATLAB software after preprocessing. The correlations between the FCD value and each of the neurocognitive outcomes were analyzed in the ALL patients. RESULTS: The group-averaged FCD maps showed similar spatial patterns between the two groups. Compared with the HCs, ALL patients showed decreased long-range FCD in regions of the bilateral lingual gyrus, cingulate cortex, hippocampal gyrus, and right calcarine fissure. Simultaneously, decreased regions in the short-range FCD map were the bilateral lingual gyrus, cingulate cortex, parahippocampal gyrus and right calcarine fissure. Increased functional connectivity (FC) was observed between the region with decreased long-range FCD and the posterior cerebellar lobe, and decreased FC was observed between the region and the middle occipital gyrus, cuneus and lingual gyrus. Thus, there existed no brain areas with increased FCD. The decreased short-range FCD value of ALL patients was positively correlated with the score on the Digit Span Test (Forward), and the increased FC value was negatively correlated with the score on the Trail Making Test part A. CONCLUSION: Our results suggest the altered functional connectivity of young survivors of ALL in the posterior region of the brain and posterior lobe of the cerebellum. Alterations in spontaneous neuronal activity seem to parallel the neurocognitive testing, which indicates that the rs-fMRI could be used as a neuroimaging marker for neurological impairment in ALL patients.

The efficacy of dexketoprofen for migraine attack: A meta-analysis of randomized controlled studies.

BACKGROUND: The efficacy of dexketoprofen for migraine attack remains controversial. We conduct a systematic review and meta-analysis to explore the influence of dexketoprofen supplementation versus placebo on pain control in migraine attack patients. METHODS: We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through March 2019 for randomized controlled trials (RCTs) assessing the effect of dexketoprofen supplementation versus placebo on pain control for migraine attack patients. This meta-analysis is performed using the random-effect model. RESULTS: Five RCTs involving 794 patients are included in the meta-analysis. Overall, compared with control group for migraine attack, dexketoprofen supplementation is associated with substantially increased pain free at 2 hours (RR = 1.90; 95% CI = 1.43-2.53; P < .0001), pain free at 48 hours (RR = 1.63; 95% CI = 1.07-2.49; P = .02), good or excellent treatment (RR = 1.48; 95% CI = 1.24-1.78; P < .0001) and pain relief at 2 hours (RR = 1.80; 95% CI = 1.17-2.77; P = .007), as well as reduced need for rescue drug (RR = 0.64; 95% CI = 0.43-0.94; P = .02), with no significant increase in adverse events (RR = 1.51; 95% CI = 0.87-2.62; P = .14). CONCLUSION: Dexketoprofen supplementation benefits to improve pain control at 48 hours and reduce the need for rescue drug in migraine attack patients.

The Efficacy of Mesenchymal Stem Cells for Cardiomyopathy: A Meta-analysis of Randomized Controlled Trials.

INTRODUCTION: The efficacy of mesenchymal stem cells (MSCs) for cardiomyopathy remains controversial. We conducted a systematic review and meta-analysis to explore the influence of MSCs versus placebo on the treatment efficacy of cardiomyopathy. METHODS: We searched PubMed, EMbase, Web of Science, EBSCO, and Cochrane Library databases through November 2018 for randomized controlled trials (RCTs) assessing the treatment efficacy of MSCs versus placebo for cardiomyopathy. This meta-analysis was performed using the random-effect model. RESULTS: Five RCTs were included in the meta-analysis. Overall, compared with the control group for cardiomyopathy, MSCs treatment showed significantly positive effect on LVEF (MD = 5.85; 95% CI = 3.88 to 7.83; P < .00001), NYHA classification (MD = -1.11; 95% CI = -1.45 to -0.77; P < .00001), LVEDd (MD = -3.00; 95% CI = -5.37 to -0.64; P = .01), and the proportion of fixed defects (MD = -4.22; 95% CI = -6.91 to -1.52; P = .002), but had no obvious influence on death (RR = 0.42; 95% CI = 0.12 to 1.50; P = 0.18) or adverse events (RR = 1.14; 95% CI = 0.70 to 1.86; P = .59). CONCLUSION: MSCs treatment showed favorable impact on LVEF, NYHA classification, LVEDd, and the proportion of fixed defects for cardiomyopathy patients.