Tracing volitional recovery in post-stroke akinetic mutism using longitudinal microstructure imaging: Insights from a single case study.

Lesions in the frontal-subcortical circuitry can lead to akinetic mutism (AM) characterized by diminished volition. However, the microstructural changes in the damaged network underlying its recovery remain unknown. Clinical examination and neuropsychological assessment were performed on a patient with post-stroke AM. Multimodal MRI scans were performed at baseline and follow-ups. We used diffusion MRI and biophysical models, specifically utilizing neurite orientation dispersion and density imaging for assessing gray matter microstructure, and fixel-based analysis for the evaluation of white matter. Longitudinal comparisons were performed between the patient and healthy controls. Pronounced recovery of volition was observed after dopamine agonist therapy combined with physical therapy. In addition to infarcts in the bilateral medial cortex, microstructure imaging detected reduced neurite density in extensive areas, specifically in temporal areas and subcortical nuclei, and decreased fiber density of white matter tracts (TFCE-corrected p < .05). Microstructural degeneration in the anterior cingulate cortex and cingulum was relatively persistent (Bonferroni-corrected p < .05). However, most tracts within the frontal-subcortical circuitry showed increased fiber density during the recovery stage. Microstructure of an extensive network may contribute to the disruption and recovery of volition. Fiber density within the frontal-subcortical circuitry could be a promising biomarker indicating volitional recovery.

Influence of prenatal aquatic activities on fetal outcomes and maternal physical and mental outcomes: a systematic review and meta-analysis.

BACKGROUND: Aquatic activities are becoming increasingly popular as a form of exercise during pregnancy. However, the effects of these activities on the physical and mental health outcomes of pregnant women during and after pregnancy as well as fetal outcomes remain unclear. This meta-analysis evaluated the current evidence regarding the effects of aquatic activities during pregnancy on neonatal and maternal outcomes. METHODS: Three databases (PubMed, Cochrane Central electronic database, Embase) were searched from inception to July 17, 2024 for randomized controlled trials (RCTs) comparing the effects of aquatic activities versus standard prenatal care or no exercise on neonatal and maternal outcomes. Pooled outcome measures were determined using random-effects models. RESULTS: Ten RCTs including 1949 patients met the criteria for inclusion in this meta-analysis. The results showed that prenatal aquatic activities could significantly improve maternal weight control (mean difference [MD]= -0.91, 95% confidence interval [CI]= -1.64 to -0.18, P = 0.01, I2 = 0.00%), improve maternal quality of life (standard mean difference [SMD] = 0.16, 95%CI = 0.03 to 0.28, P = 0.01, I2 = 0.00%), and extend fetal birth length (MD = 0.48, 95%CI = 0.10 to 0.87, P = 0.01, I2 = 0.00%) compared with standard prenatal care or no exercise, while no significant differences were observed in fetal birth weight, Apgar score at 1 min, Apgar score at 5 min, pH of umbilical cord blood, gestational age, rate of preterm delivery, incidence of postnatal depression and mode of delivery. CONCLUSIONS: Prenatal aquatic activities can significantly improve maternal weight control and quality of life during pregnancy, and may promote longer birth length. However, additional studies are needed to confirm these findings.

Catheter and Non-Catheter-Related Venous Thromboembolism in Cancer Patients: Survival, Anticoagulation Efficacy, and Safety.

PURPOSE: To investigate the differences in survival after venous thromboembolism (VTE) and anticoagulation efficacy and safety between catheter (CRVTE) and non-catheter-related VTE (NCRVTE) in cancer patients. METHODS: A retrospective research was conducted, and consecutive cancer (digestive, respiratory, genitourinary, blood and lymphatic, and the other cancers) patients with VTE were enrolled. The anticoagulation therapies included low-molecular-weight heparin (LMWH), warfarin, new type of direct oral anticoagulants (NDOACs), LMWH combined with warfarin, and LMWH combined with NDOACs. Data were collected from the electronic medical record database of our hospital and were analyzed accordingly by Kruskal-Wallis H Test, Chi-square test, Fisher's exact test, Logistic regressions, Kaplan-Meier analysis, and Cox regressions. RESULTS: 263 patients were included, median age in years (interquartile range) was 64(56-71) and 60.5% were male. VTE recurrence rate was 16.7% in CRVTE group which was significantly lower than 34.8% in NCRVTE group (P = .032). Heart diseases were independently associated with VTE recurrence (P = .025). Kaplan-Meier survival estimates at 1, 2, and 3 years for CRVTE group were 62.5%, 60.0%, and 47.5%, respectively, compared with 47.9% (P = .130), 38.7% (P = .028), and 30.1% (P = .046), respectively, for NCRVTE group. Cox regression showed surgery (P = .003), anticoagulation therapy types (P = .009), VTE types (P = .006) and cancer types (P = .039) were independent prognostic factors for 3-year survival after VTE. Nonmajor and major bleeding were not significantly different (P = .417). Anticoagulation therapy types were independently associated with the bleeding events (P = .030). CONCLUSIONS: Cancer patients with CRVTE potentially have a better anticoagulation efficacy and survival compared to NCRVTE, and the anticoagulation safety seems no significant difference.

Point-of-care ultrasound in the diagnosis and treatment of Budd-Chiari syndrome: A rare case report and literature review.

Budd-Chiari syndrome (BCS) is a life-threatening disease characterized by the partial or complete obstruction of hepatic venous outflow anywhere from the liver to the heart. In China, secondary BCS is rare. We present a case of secondary BCS caused by compression of the suprahepatic inferior vena cava (IVC), mainly due to local bile accumulation in the caudate lobe of the liver. This case highlights the scarcity of secondary BCS worldwide and the importance of point-of-care ultrasound (POCUS) in the diagnosis and treatment, especially in critical and comatose patients. Prompt diagnosis and recanalization with POCUS-guided puncture and drainage help improve patient prognosis.

Dysregulation of parvalbumin expression and neurotransmitter imbalance in the auditory cortex of the BTBR mouse model of autism spectrum disorder.

Individuals diagnosed with autism spectrum disorder (ASD) frequently exhibit abnormalities in auditory perception, a phenomenon potentially attributed to alterations in the excitatory and inhibitory cells constituting cortical circuits. However, the exact genetic factors and cell types affected by ASD remain unclear. The present study investigated the balance of excitatory and inhibitory activity in the auditory cortex using BTBR T+ Itpr3tf/J (BTBR) mice, a well-established model for autism research. Our investigation unveiled a reduction in parvalbumin-positive (PV+) neurons within the AC of BTBR mice. Remarkably, in vivo magnetic resonance spectroscopy studies disclosed an elevation in glutamate (Glu) levels alongside a decrement in γ-aminobutyric acid (GABA) levels in this cortical region. Additionally, transcriptomic analysis of the mouse model facilitated the classification of several ASD-associated genes based on their cellular function and pathways. By comparing autism risk genes with RNA transcriptome sequencing data from the ASD mouse model, we identified the recurrent target gene Scn1a and performed validation. Intriguingly, we uncovered the specific expression of Scn1a in cortical inhibitory neurons. These findings hold significant value for understanding the underlying neural mechanisms of abnormal sensory perception in animal models of ASD.

Effects of mind-body interventions on polycystic ovary syndrome: a comprehensive meta-analysis.

BACKGROUND: Mind-body interventions (MBI) have emerged as a potential therapeutic approach, but their effectiveness in the treatment of Polycystic Ovary Syndrome (PCOS) remains inconclusive. This study systematically evaluates the effectiveness of MBI on quality of life, anthropometry, androgen secretion, glucose, and lipid metabolism in PCOS. METHODS: A computer search was conducted across three databases: PubMed, the Cochrane Library, and EMBASE, to identify randomized controlled trials (RCTs) related to MBI for PCOS from their inception until July 2024. DerSimonian and Laird's random-effects model and Stata 17.0 software was employed for our meta-analysis. RESULTS: Twelve RCTs were included. MBI significantly improved PCOSQ subscale scores, including emotional disturbances (MD: 7.75, 95% CI: 6.10 to 9.40), body hair (MD: 2.73, 95% CI: 0.54 to 4.91), menstrual problems (MD: 3.79, 95% CI: 2.89 to 4.69), and weight (MD: 1.48, 95% CI: 0.03 to 2.93). Furthermore, there was a reduction in depression levels (MD: -1.53, 95% CI: -2.93 to -0.13). Sensitivity analysis confirmed the robustness of PCOSQ-Emotional disturbances and PCOSQ-Menstrual problems, with a high GRADE level of evidence for these subscales. Secondary outcome measures, including waist-hip ratio, fasting blood glucose, and HOMA-IR exhibited statistically significant differences. Subgroup analysis revealed that obesity could influence treatment outcomes. CONCLUSION: MBI can serve as an alternative therapy, modulating effect on the quality of life and depression in PCOS patients. Future well-designed, high-quality, and large-scale studies should be conducted to thoroughly assess the impact of different Mind-Body Interventions (MBI) on various PCOS phenotypes. TRIAL REGISTRATION: PROSPERO (CRD42023472035).

Acupuncture for poststroke coma: A systematic review and meta-analysis.

BACKGROUND: Despite being widely applied in clinical practice, the wake-promoting effect of acupuncture in poststroke coma patients remains controversial. OBJECTIVE: This study aimed to evaluate the efficacy of acupuncture for the treatment of poststroke coma. METHODS: Randomized controlled trials (RCTs) of acupuncture for treating poststroke coma were identified in PubMed, Cochrane Library, EMBASE, CNKI, WanFang and VIP up to 25 November 2023. The main outcomes were Glasgow Coma Scale (GCS) score, National Institute of Health Stroke Scale (NIHSS) score, awakening ratio and clinically effective ratio. Stata 17 and Review Manager 5.4 software were used for mate analysis. RESULTS: A total of 34 RCTs involving 2757 patients were included. GCS (WMD = 1.78; 95% CI: 1.35 to 2.21) and NIHSS score (WMD = -2.84; 95% CI: -3.84 to -1.84) were significantly increased in acupuncture group compared with control group. Acupuncture combined with routine treatment may be better than routine treatment in improving the awakening ratio (RR= 1.65; 95% CI: 1.24 to 2.91) and the clinically effective ratio (RR= 1.20; 95% CI: 1.13 to 1.27). Some methodological flaws were identified in the included studies, including non-implementation of blinding, inappropriate disease assessment and heterogeneous interventions. CONCLUSIONS: The existing evidence suggests that acupuncture combined with conventional treatment may be an effective treatment for poststroke coma patients. In the meantime, more high-quality RCTs are needed to demonstrate these findings due to methodological weaknesses like randomization, blinding, heterogeneous interventions and long-term follow-up.

Pellino1 orchestrates gut-kidney axis to perpetuate septic acute kidney injury through activation of STING pathway and NLRP3 inflammasome.

AIMS: Intestinal barrier dysfunction is the initial and propagable factor of sepsis in which acute kidney injury (AKI) has been considered as a common life-threatening complication. Our recent study identifies the regulatory role of Pellino1 in tubular death under inflammatory conditions in vitro. The objective of our current study is to explore the impact of Pellino1 on gut-kidney axis during septic AKI and uncover the molecular mechanism (s) underlying this process. MATERIALS AND METHODS: Immunohistochemistry (IHC) was conducted to evaluate Pellino1 and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) levels in renal biopsies from critically ill patients with a clinical diagnosis of sepsis. Functional and mechanistic studies were characterized in septic models of the Peli-knockout (Peli1-/-) mice by histopathological staining, enzyme-linked immunosorbent assay (ELISA), flow cytometry, immunofluorescence, biochemical detection, CRISPR/Cas9-mediated gene editing and intestinal organoid. KEY FINDINGS: Pellino1, together with NLRP3, are highly expressed in renal biopsies from critically ill patients diagnosed with sepsis and kidney tissues of septic mice. The Peli1-/- mice with sepsis become less prone to develop AKI and have markedly compromised NLRP3 activation in kidney. Loss of Peli1 endows septic mice refractory to intestinal inflammation, barrier permeability and enterocyte apoptosis that requires stimulator of interferons genes (STING) pathway. Administration of STING agonist DMXAA deteriorates AKI and mortality of septic Peli1-/- mice in the presence of kidney-specific NLRP3 reconstitution. SIGNIFICANCE: Our studies suggest that Pellino1 has a principal role in orchestrating gut homeostasis towards renal pathophysiology, thus providing a potential therapeutic target for septic AKI.

Targeting SLC22A5 fosters mitophagy inhibition-mediated macrophage immunity against septic acute kidney injury upon CD47-SIRPα axis blockade.

Efferocytosis of apoptotic neutrophils (PMNs) by macrophages is helpful for inflammation resolution and injury repair, but the role of efferocytosis in intrinsic nature of macrophages during septic acute kidney injury (AKI) remains unknown. Here we report that CD47 and signal regulatory protein alpha (SIRPα)-the anti-efferocytotic 'don't eat me' signals-are highly expressed in peripheral blood mononuclear cells (PBMCs) from patients with septic AKI and kidney samples from mice with polymicrobial sepsis and endotoxin shock. Conditional knockout (CKO) of SIRPA in macrophages ameliorates AKI and systemic inflammation response in septic mice, accompanied by an escalation in mitophagy inhibition of macrophages. Ablation of SIRPA transcriptionally downregulates solute carrier family 22 member 5 (SLC22A5) in the lipopolysaccharide (LPS)-stimulated macrophages that efferocytose apoptotic neutrophils (PMNs). Targeting SLC22A5 renders mitophagy inhibition of macrophages in response to LPS stimuli, improves survival and deters development of septic AKI. Our study supports further clinical investigation of CD47-SIRPα signalling in sepsis and proposes that SLC22A5 might be a promising immunotherapeutic target for septic AKI.

A neutrophil elastase inhibitor, sivelestat, attenuates sepsis-induced acute kidney injury by inhibiting oxidative stress.

Background: Sivelestat, a selective inhibitor of neutrophil elastase (NE), can mitigate sepsis-related acute lung injury. However, the role of sivelestat in inhibiting oxidative stress and attenuating sepsis-related acute kidney injury (AKI) remains unclear. Here, we reported the effects of sivelestat against oxidative stress-induced AKI by suppressing the production of oxidative stress indicators. Materials and methods: A male Sprague-Dawley rat model of sepsis was established by cecal ligation and puncture (CLP). Sivelestat or normal saline was administered into jugular vein with a sustained-release drug delivery system. Indicators of inflammation and AKI, including white blood cells (WBC), neutrophils, lymphocytes, C-reactive proteins (CRP), procalcitonin (PCT), blood urea nitrogen (BUN), creatinine (Cr) and uric acid (UA), were assessed at 24 h post-sivelestat treatment. Indicators of liver injury, including direct bilirubin (DBIL), indirect bilirubin (IBIL), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), were also assessed at 24 h post-sivelestat treatment. Indicators of oxidative stress, including superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px), were assessed at 12 h and 24 h post-sivelestat treatment. At 24 h post-sivelestat treatment, H&E staining of kidney and liver tissue was performed to observe pathological alterations. Results: At 24 h post normal saline or sivelestat (0.2 g/kg body weight) treatment, WBC, neutrophil, CRP, PCT, MDA, BUN, Cr, UA, AST, ALT, DBIL and IBIL were increased, while SOD and GSH-Px were decreased, in septic rats treated with normal saline compared with that in non-septic rats treated with normal saline (all p < 0.05). The changes of these indicators were reversed in septic rats treated with sivelestat compared with that in septic rats treated with normal saline (all p < 0.05). Similar results were found regarding the levels of oxidative stress indicators at 12 h post-sivelestat treatment. The degenerative histopathological changes in both kidney and liver tissues were ameliorated upon sivelestat treatment. Conclusions: Sivelestat plays a protective role in sepsis-related AKI by inhibiting oxidative stress. Our study reveals a possible therapeutic potential of sivelestat for oxidative stress-induced AKI.

Effects of whole-body vibration training on physical function, activities of daily living, and quality of life in patients with stroke: a systematic review and meta-analysis.

Purpose: This systematic review and meta-analysis aimed to evaluate the efficacy of whole-body vibration training (WBVT) in patients with stroke, specifically focusing on its effects on physical function, activities of daily living (ADL), and quality of life (QOL). Additionally, potential moderators influencing WBVT outcomes were explored. Methods: We conducted a systematic search of PubMed, Embase, and Cochrane Library from inception to September 2022. Eligible studies were randomized controlled trials employing WBVT in patients with stroke. Two investigators independently extracted the data and calculated the standardized mean difference (SMD) using random-effect models. Results: Twenty-five studies involving 991 patients were included in this meta-analysis. WBVT demonstrated significant reductions in spasticity (SMD = -0.33, 95% CI = -0.61 to -0.06, p = 0.02), improvements in motor function (SMD = 0.39, 95% CI = 0.16 to 0.61, p < 0.01), and enhancements in balance function (SMD = 0.28, 95% CI = 0.09 to 0.47, p < 0.01) in patients with stroke. However, no significant effects were observed for gait (SMD = -0.23, 95% CI = -0.50 to 0.04, p = 0.10), ADL (SMD = -0.01, 95% CI = -0.46 to 0.44, p = 0.97), or QOL (SMD = 0.12, 95% CI = -0.30 to 0.53, p = 0.59). Subgroup analyses revealed that variable frequency vibration and side-alternating vibration exhibited significant efficacy in reducing spasticity and improving motor and balance functions, while fixed frequency vibration and vertical vibration did not yield significant therapeutic benefits in these domains. Conclusion: Our findings indicate that WBVT may serve as a viable adjunct therapy for stroke patients to alleviate spasticity and enhance motor and balance functions. Variable frequency and side-alternating vibration appear to be crucial factors influencing the therapeutic effects of WBVT on these dysfunctions. Nonetheless, WBVT did not show significant effects on gait, ADL, or QOL in stroke patients. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier (CRD42022384319).

Electromyographic biofeedback therapy for improving limb function after stroke: A systematic review and meta-analysis.

BACKGROUND: Upper and lower limb impairment is common after stroke. Electromyographic biofeedback therapy is a non-invasive treatment, and its effectiveness in functional rehabilitation of the limb after stroke still remains uncertain. OBJECTIVE: The objective of this study was to evaluate whether electromyographic biofeedback can improve upper and lower limb dysfunction in stroke patients. METHODS: PubMed, Embase, Cochrane Library, and Physiotherapy Evidence Database (PEDro) were searched from inception to 1st May 2022. Inclusion criteria were randomized controlled clinical trials of electromyographic biofeedback therapy interventions reporting changes in upper and lower limb function in post-stroke patients. Data were extracted by two independent reviewers and pooled in random-effects models using Review manager (RevMan) software. RESULTS: Our analyses included 10 studies enrolling a total of 303 participants. Electromyographic biofeedback therapy can effectively improve limb function after stroke (standardized mean difference [SMD], 0.44; 95% confidence interval [CI], 0.12-0.77; P = 0.008) and in subgroup analyses, the effect sizes of short-term effect (SMD, 0.33; 95% CI, 0.02-0.64; P = 0.04) was significant, but the long-term was not (SMD, 0.61; 95% CI, -0.11-1.33; P = 0.10). In addition, Electromyographic biofeedback therapy can improve the active range of motion of shoulder (SMD, 1.49; 95% CI, 2.22; P<0.0001) and wrist joints (SMD, 0.77; 95% CI, 0.13-1.42; P = 0.02) after stroke. CONCLUSION: In this meta-analysis, electromyographic biofeedback therapy intervention can improve upper and lower limb function in patients with stroke. Short-term (less than one month) improvement after electromyographic biofeedback therapy was supported, while evidence for long-term (more than one month) benefits was lacking. Range of motion in the glenohumeral and wrist joints were improved. Stronger evidence for individualized parameters, such as optimal treatment parameters and intervention period, is needed in the future. SYSTEMATIC REVIEW REGISTRATION: [https://www.crd.york.ac.uk/prospero/display_record.php?recordID=267596], identifier [CRD42022354363].

NODDI Identifies Cognitive Associations with In Vivo Microstructural Changes in Remote Cortical Regions and Thalamocortical Pathways in Thalamic Stroke.

The roles of cerebral structures distal to isolated thalamic infarcts in cognitive deficits remain unclear. We aimed to identify the in vivo microstructural characteristics of remote gray matter (GM) and thalamic pathways and elucidate their roles across cognitive domains. Patients with isolated ischemic thalamic stroke and healthy controls underwent neuropsychological assessment and magnetic resonance imaging. Neurite orientation dispersion and density imaging (NODDI) was modeled to derive the intracellular volume fraction (VFic) and orientation dispersion index. Fiber density (FD) was determined by constrained spherical deconvolution, and tensor-derived fractional anisotropy (FA) was calculated. Voxel-wise GM analysis and thalamic pathway tractography were performed. Twenty-six patients and 26 healthy controls were included. Patients exhibited reduced VFic in remote GM regions, including ipsilesional insular and temporal subregions. The microstructural metrics VFic, FD, and FA within ipsilesional thalamic pathways decreased (false discovery rate [FDR]-p < 0.05). Noteworthy associations emerged as VFic within insular cortices (ρ = -0.791 to -0.630; FDR-p < 0.05) and FD in tracts connecting the thalamus and insula (ρ = 0.830 to 0.971; FDR-p < 0.001) were closely associated with executive function. The VFic in Brodmann area 52 (ρ = -0.839; FDR-p = 0.005) and FA within its thalamic pathway (ρ = -0.799; FDR-p = 0.003) correlated with total auditory memory scores. In conclusion, NODDI revealed neurite loss in remote normal-appearing GM regions and ipsilesional thalamic pathways in thalamic stroke. Reduced cortical dendritic density and axonal density of thalamocortical tracts in specific subregions were associated with improved cognitive functions. Subacute microstructural alterations beyond focal thalamic infarcts might reflect beneficial remodeling indicating post-stroke plasticity.

Effects of vibration therapy for post-stroke spasticity: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The efficacy of vibration therapy (VT) in people with post-stroke spasticity (PSS) remains uncertain. This study aims to conduct a comprehensive meta-analysis to assess the effectiveness of VT in PSS. METHODS: PubMed, Embase, Cochrane Library, Physiotherapy Evidence Database, and Web of Science were searched from inception to October 2022 for randomized controlled trials (RCTs) of VT in people with PSS. The primary outcome was spasticity, and secondary outcomes included pain, motor function, gait performance, and adverse events. A meta­analysis was performed by pooling the standardized mean difference (SMD) with 95% confidence intervals (CI). RESULTS: A total of 12 studies met the inclusion criteria. Overall, VT had significant effects on reducing spasticity (SMD = - 0.77, 95% CI - 1.17 to - 0.36, P < 0.01) and pain (SMD = - 1.09, 95% CI - 1.74 to - 0.45, P < 0.01), and improving motor function (SMD = 0.42, 95% CI 0.21 to 0.64, P < 0.01) in people with PSS. However, VT had no significant effect on gait performance (SMD = - 0.23, 95% CI - 0.56-0.10). In addition, subgroup differences in short-term anti-spasticity effects between different vibration subtypes, vibration frequencies, vibration durations, frequency of sessions, control therapy, spasticity distribution, and population classification were not significant. CONCLUSION: We found that VT significantly alleviated spasticity and pain in people with PSS and improved motor function, but its effect on gait performance was unclear. However, further studies are needed to validate these findings.

P2Y12 receptor mediates apoptosis and demyelination to affect functional recovery in mice with spinal cord injury.

Among diseases of the central nervous system (CNS), spinal cord injury (SCI) has a high fatality rate. It has been proven that P2Y G protein-coupled purinergic receptors have a neuroprotective role in apoptosis and regeneration inside the damaged spinal cord. The P2Y12 receptor (P2Y12R) has recently been linked to peripheral neuropathy and stroke. However, the role of P2Y12R after SCI remains unclear. Our study randomly divided C57BL/6J female mice into 3 groups: Sham+DMSO, SCI+DMSO, and SCI+MRS2395. MRS2395 as a P2Y12R inhibitor was intraperitoneally injected at a dose of 1.5 mg/kg once daily for 7 days. We showed that the P2Y12R was markedly activated after injury, and it was double labeled with the microglial and neuron. Behavioral tests were employed to assess motor function recovery. By using immunofluorescence staining, the NeuN expression level was detected. The morphology of neurons was observed by hematoxylin-eosin and Nissl staining. P2Y12R, Bax, GFAP, PCNA and calbindin expression levels were detected using Western blot. Meanwhile, mitochondria and myelin sheath were observed by transmission electron microscopy (TEM). Our findings demonstrated that MRS2395 significantly enhanced motor function induced by SCI and that was used to alleviate apoptosis and astrocyte scarring. NeuN positive cells in the SCI group were lower than in the therapy group, although Bax, GFAP, PCNA and calbindin expression levels were considerably higher. Moreover, following MRS2395 therapy, the histological damage was reversed. A notable improvement in myelin sheath and mitochondrial morphology was seen in the therapy group. Together, our findings indicate that activation of P2Y12R in damaged spinal cord may be a critical event and suggest that inhibition of P2Y12R might be a feasible therapeutic strategy for treating SCI.

10 Hz repetitive transcranial magnetic stimulation (rTMS) may improve cognitive function: An exploratory study of schizophrenia patients with auditory hallucinations.

Objectives: Cognitive impairment in schizophrenia patients with auditory hallucinations is more prominent compared to those without. Our study aimed to investigate the cognitive improvement effects of 10 Hz repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) in schizophrenia with auditory hallucinations. Methods: A total of 60 schizophrenic patients with auditory hallucinations in this study were randomly assigned to sham or active group. Both groups received 10 Hz or sham rTMS targeted in left DLPFC for 20 sessions. The Positive and Negative Syndrome Scale (PANSS), the Auditory Hallucination Rating Scale (AHRS), the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and the Udvalg for Kliniske Under-sogelser (UKU) side effect scale were used to measure psychiatric symptoms, auditory hallucinations, cognition, and side reaction, respectively. Results: Our results indicated that the active group experienced greater improvements in RBANS-total score (P = 0.043) and immediate memory subscale score (P = 0.001). Additionally, the PANSS-total score, negative and positive subscale score were obviously lower in the active group compared to the sham group (all P < 0.050). Furthermore, our study found that the improvement of RBANS-total score was positively associated with the decline of positive factor score, and the improvement of language score in RBANS was positively associated with the reduction in PANSS-total scale, negative and positive subscale score in the real stimulation group (all P < 0.050). Conclusion: Our results demonstrated that a four-week intervention of 10 Hz rTMS over the left DLPFC can improve cognition (particularly immediate memory) among schizophrenia patients with auditory hallucinations. Future studies with larger sample size are needful to verify our preliminary findings.

Disentangling in-vivo microstructural changes of white and gray matter in mild cognitive impairment and Alzheimer's disease: a systematic review and meta-analysis.

The microstructural characteristics of white and gray matter in mild cognitive impairment (MCI) and the early-stage of Alzheimer's disease (AD) remain unclear. This study aimed to systematically identify the microstructural damages of MCI/AD in studies using neurite orientation dispersion and density imaging (NODDI), and explore their correlations with cognitive performance. Multiple databases were searched for eligible studies. The 10 eligible NODDI studies were finally included. Patients with MCI/AD showed overall significant reductions in neurite density index (NDI) of specific white matter structures in bilateral hemispheres (left hemisphere: -0.40 [-0.53, -0.27], P < 0.001; right: -0.33 [-0.47, -0.19], P < 0.001), involving the bilateral superior longitudinal fasciculus (SLF), uncinate fasciculus (UF), the left posterior thalamic radiation (PTR), and the left cingulum. White matter regions exhibited significant increased orientation dispersion index (ODI) (left: 0.25 [0.02, 0.48], P < 0.05; right: 0.27 [0.07, 0.46], P < 0.05), including the left cingulum, the right UF, and the bilateral parahippocampal cingulum (PHC), and PTR. Additionally, the ODI of gray matter showed significant reduction in bilateral hippocampi (left: -0.97 [-1.42, -0.51], P < 0.001; right: -0.90 [-1.35, -0.45], P < 0.001). The cognitive performance in MCI/AD was significantly associated with NDI (r = 0.50, P < 0.001). Our findings highlight the microstructural changes in MCI/AD were characterized by decreased fiber orientation dispersion in the hippocampus, and decreased neurite density and increased fiber orientation dispersion in specific white matter tracts, including the cingulum, UF, and PTR. Moreover, the decreased NDI may indicate the declined cognitive level of MCI/AD patients.

Effects of synovial macrophages in osteoarthritis.

Osteoarthritis (OA) is a common degenerative disease in mammals. However, its pathogenesis remains unclear. Studies indicate that OA is not only an aging process that but also an inflammation-related disease. Synovitis is closely related to the progression of OA, and synovial macrophages are crucial participants in synovitis. Instead of being a homogeneous population, macrophages are polarized into M1 or M2 subtypes in OA synovial tissues. Polarization is highly associated with OA severity. However, the M1/M2 ratio cannot be the only factor in OA prognosis because intermediate stages of macrophages also exist. To better understand the mechanism of this heterogeneous disease, OA subtypes of synovial macrophages classified by gene expression were examined. Synovial macrophages do not act alone; they interact with surrounding cells such as synovial fibroblasts, osteoclasts, chondrocytes, lymphocytes and even adipose cells through a paracrine approach to exacerbate OA. Treatments targeting synovial macrophages and their polarization are effective in relieving pain and protecting cartilage during OA development. In this review, we describe how synovial macrophages and their different polarization states influence the progression of OA. We summarize the current knowledge of the interactions between macrophages and other joint cells and examine the current research on new medications targeting synovial macrophages.

Resveratrol inhibits ferroptosis via activating NRF2/GPX4 pathway in mice with spinal cord injury.

Ferroptosis is a newly defined form of cell death involved in neurologic disease. Resveratrol is a non-flavonoid polyphenolic compound with anti-inflammatory and antioxidant properties, but its potential therapeutic mechanism in spinal cord injury (SCI) remains unknown. Therefore, this study evaluates the mechanism by which resveratrol promotes neurological and motor function recovery in mice with SCI. The motor function of mice was evaluated using the Basso Mouse Scale score and footprint test. The effect of resveratrol on the neuronal cell state was observed using NeuN, fluoro-Jade C, and Nissl staining. The expression of iron content in injured segments was observed using Perls blue and Diaminobenzidine staining. The effect of resveratrol on the levels of malondialdehyde, glutathione, Fe2+ , and glutathione peroxidase 4 enzyme activity was also investigated. The mitochondrial ultrastructures of injured segment cells were observed using transmission electron microscope, while the protein levels of ferroptosis-related targets were detected using Western blot. Our findings show that resveratrol improves motor function after SCI and has certain neuroprotective effects; in ferroptosis-related studies, resveratrol inhibited the expression of ferroptosis-related proteins and ions. Resveratrol improved changes in mitochondrial morphology. Mechanistically, the Nrf2 inhibitor ML385 reversed the inhibitory effect of resveratrol on ferroptosis-related genes, indicating that resveratrol inhibits ferroptosis through the Nrf2/GPX4 pathway. Our findings elucidate that resveratrol promotes functional recovery, inhibits ferroptosis post-SCI, and provides an experimental basis for subsequent clinical translational research. Our study shows that resveratrol inhibits the production of lipid peroxide and the accumulation of iron by activating Nrf2/GPX4 signaling pathway, thereby inhibiting neuronal ferroptosis. At the same time, it can promote the recovery of motor function of mice.

Bibliometric Analysis of Global Research on Transient Receptor Potential Vanilloid 1 in the Field of Pain.

Background: Transient Receptor Potential Vanilloid 1 (TRPV1) is a heat-activated cation channel modulated by inflammatory mediators, which is closely related to pain and serves as a potential analgesic target. However, the bibliometric analyses summarizing TRPV1 in the field of pain are scarce. This study aims to summarize the current status of TRPV1 in pain and the potential research direction. Methods: Articles regarding TRPV1 in the pain field between 2013 and 2022 were extracted from the Web of Science core collection database on 31 December 2022. Scientometric software (VOSviewer and CiteSpace 6.1.R6) were used to perform bibliometric analysis. This study provided data on the trend of the annual outputs, countries/regions, institutions, journals, authors, co-cited references and keywords. Results: A total of 2462 publications related to TRPV1 in the field of pain were extracted from 2013 to 2022, which were written by 12,005 authors of 2304 institutions, 68 countries/regions in 686 journals, with 48,723 citations totally. The number of publications has grown rapidly over the past 10 years. Most publications were from the USA and China; the Seoul Natl Univ was the most active institution; Tominaga M published the most papers and Caterina MJ was the most productive co-cited author; The top-contributing journal was Pain; The most cited references was the article authored by Julius D. "Neuropathic pain", "inflammatory pain", "visceral pain" and "migraine" were the most common types of pain in this field. The mechanism of TRPV1 in pain was one of the main research directions. Conclusion: This study presented an overview of the major research directions of TRPV1 in the pain field by bibliometric methods over the past decade. The results could reveal the research trends and the hotspots in the field and provide helpful information for clinical treatments of pain.