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.

Cerebral perfusion mediated by thalamo-cortical functional connectivity in non-dominant thalamus affects naming ability in aphasia.

Naming is a commonly impaired language domain in various types of aphasia. Emerging evidence supports the cortico-subcortical circuitry subserving naming processing, although neurovascular regulation of the non-dominant thalamic and basal ganglia subregions underlying post-stroke naming difficulty remains unclear. Data from 25 subacute stroke patients and 26 age-, sex-, and education-matched healthy volunteers were analyzed. Region-of-interest-wise functional connectivity (FC) was calculated to measure the strength of cortico-subcortical connections. Cerebral blood flow (CBF) was determined to reflect perfusion levels. Correlation and mediation analyses were performed to identify the relationship between cortico-subcortical connectivity, regional cerebral perfusion, and naming performance. We observed increased right-hemispheric subcortical connectivity in patients. FC between the right posterior superior temporal sulcus (pSTS) and lateral/medial prefrontal thalamus (lPFtha/mPFtha) exhibited significantly negative correlations with total naming score. Trend-level increased CBF in subcortical nuclei, including that in the right lPFtha, and significant negative correlations between naming and regional perfusion of the right lPFtha were observed. The relationship between CBF in the right lPFtha and naming was fully mediated by the lPFtha-pSTS connectivity in the non-dominant hemisphere. Our findings suggest that perfusion changes in the right thalamic subregions affect naming performance through thalamo-cortical circuits in post-stroke aphasia. This study highlights the neurovascular pathophysiology of the non-dominant hemisphere and demonstrates thalamic involvement in naming after stroke.

Effect of Acupuncture Treatment on Post-stroke Depression by Using Diamond-Like Ultra-Thin Nano-Coating Technology.

This study aimed to explore the effect of acupuncture on account of composite diamond-like nano-membrane sensors (DLNF) sensors on post-stroke depression. Titanium/antigen-diamond-like carbon (Ti/Ag-DLC) composite DLNF sensors were prepared by coating Ti and Ag composites on the surface of DLC by radio frequency magnetron sputtering technology. The scanning electron microscope (SEM), X-ray photoelectron spectrometer (XPS), Raman spectrometer, nanoindenter, and sliding friction tester were adopted to analyze the characterization of Ti/Ag-DLC composite membrane, the chemical state of the main constituent elements on the surface, structural characteristics, membrane hardness, and tribological properties, respectively. 132 patients with post-stroke depression in our hospital were selected as the research objects, they were divided into the control group (receiving conventional treatment) and the acupuncture group (receiving acupuncture based on conventional treatment) according to different treatment methods, with 66 cases in each group. The depression of the two groups of patients before the treatment and 4 and 8 weeks after the treatment were compared. The psychological resilience scale and Herth scale were used to evaluate the mental toughness and hope level of patients. The results showed that when the Ag content was less than 0.55%, the Ti/Ag-DLC composite surface was smooth and showed no obvious particles, the membranes with different content had obvious absorption peaks at 1560 cm-1 and the friction life in a high vacuum environment was extended to around 900 revolutions. After 4 and 8 weeks of treatment, the scores of the hammer depression scale (HDS) in the two groups were significantly lower than before treatment (P<0.01) and the scores of the acupuncture group were much lower after 4 and 8 weeks of treatment in contrast to the control group (P<0.01). The optimism, self-strength, and tenacity in the psychological resilience scale of the acupuncture group patients rose higher than those in the control group (P<0.05) after 8 weeks of treatment. The Herth scale score of the acupuncture group was greatly higher compared with that of the control group after 8 weeks of treatment (P<0.01). It showed that the Ti/Ag-DLC composite DLNF sensor with good hardness and friction performance was prepared in this study. Acupuncture therapy could improve the negative emotions of patients with post-stroke depression, enhance mental resilience, and help raise the level of hope. Therefore, it was proved to be a potentially effective treatment.

P2Y2 Receptor Mediated Neuronal Regeneration and Angiogenesis to Affect Functional Recovery in Rats with Spinal Cord Injury.

The aim of this study was to investigate the effect of the P2Y2 receptor (P2Y2R) signaling pathway on neuronal regeneration and angiogenesis during spinal cord injury (SCI). The rats were randomly divided into 3 groups, including the sham+dimethyl sulfoxide (DMSO), SCI+DMSO, and SCI+P2Y2R groups. The SCI animal models were constructed. A locomotor rating scale was used for behavioral assessments. The apoptosis of spinal cord tissues was detected by TUNEL staining. The expression levels of P2Y2R, GFAP, nestin, Tuj1, and CD34 were detected by immunofluorescence staining, and the expression levels of TNF-α, IL-1ß, and IL-6 were detected by enzyme-linked immunosorbent assay. The locomotor score in the model group was significantly lower than the sham group. The expression of P2Y2R was increased after SCI. The expression levels of TNF-α, IL-1ß, and IL-6 were increased remarkably in the SCI model group compared with the sham group. The P2Y2R inhibitor relieved neuronal inflammation after SCI. Compared with the sham group, the apoptotic rate of spinal cord tissue cells in the model group was significantly increased. The P2Y2R inhibitor reduced the apoptosis of the spinal cord tissue. The expressions of CD34, Tuj1, and nestin in the model group were decreased, while the expressions of GFAP and P2Y2R were increased. The P2Y2R inhibitor reversed their expression levels. The P2Y2R inhibitor could alleviate SCI by relieving the neuronal inflammation, inhibiting the spinal cord tissue apoptosis, and promoting neuronal differentiation and vascular proliferation after SCI. P2Y2R may serve as a target for the treatment of SCI.

[The measurements of the similarity of dynamic brain functional network].

Brain functional network changes over time along with the process of brain development, disease, and aging. However, most of the available measurements for evaluation of the difference (or similarity) between the individual brain functional networks are for charactering static networks, which do not work with the dynamic characteristics of the brain networks that typically involve a long-span and large-scale evolution over the time. The current study proposes an index for measuring the similarity of dynamic brain networks, named as dynamic network similarity (DNS). It measures the similarity by combining the "evolutional" and "structural" properties of the dynamic network. Four sets of simulated dynamic networks with different evolutional and structural properties (varying amplitude of changes, trend of changes, distribution of connectivity strength, range of connectivity strength) were generated to validate the performance of DNS. In addition, real world imaging datasets, acquired from 13 stroke patients who were treated by transcranial direct current stimulation (tDCS), were used to further validate the proposed method and compared with the traditional similarity measurements that were developed for static network similarity. The results showed that DNS was significantly correlated with the varying amplitude of changes, trend of changes, distribution of connectivity strength and range of connectivity strength of the dynamic networks. DNS was able to appropriately measure the significant similarity of the dynamics of network changes over the time for the patients before and after the tDCS treatments. However, the traditional methods failed, which showed significantly differences between the data before and after the tDCS treatments. The experiment results demonstrate that DNS may robustly measure the similarity of evolutional and structural properties of dynamic networks. The new method appears to be superior to the traditional methods in that the new one is capable of assessing the temporal similarity of dynamic functional imaging data.

Correlations between Dual-Pathway White Matter Alterations and Language Impairment in Patients with Aphasia: A Systematic Review and Meta-analysis.

While converging evidence suggests linguistic roles of white matter tracts, detailed associations between white matter alterations of dual pathways and language abilities remain unknown in aphasic patients. We aimed to verify language functions of dual-pathway tracts from specific domains and investigate the influence of moderators. PubMed, Web of Science, Embase, and CENTRAL were searched for studies published between January 1, 1985 and March 17, 2019. A meta-analysis of 46 studies including 1353 aphasic patients was performed by pooling correlation coefficients between linguistic domains and diffusion metrics of dual-pathway tracts. Among these tracts, the fractional anisotropy (FA) value of the left inferior fronto-occipital fasciculus predominated across most linguistic aspects, showing the strongest correlations with global severity, comprehension, naming and reading ability. The left uncinate fasciculus and inferior longitudinal fasciculus also showed significant FA - comprehension correlations. For syntactic processing, FA values of the left superior longitudinal fasciculus and arcuate fasciculus showed significant positive correlations. Meta-regression revealed no influence of etiology on FA - language correlations, while sex had a moderating effect on the FA - comprehension correlation of the arcuate fasciculus, and age influenced the FA - naming correlation in the superior longitudinal fasciculus. In conclusion, multifunctional characteristics of tracts were revealed in aphasic patients, including broad linguistic associations of the inferior fronto-occipital fasciculus, and repetition and syntactic involvement of the arcuate fasciculus. Language associations of the inferior longitudinal fasciculus and uncinate fasciculus were clarified regarding comprehension subdomains. The insignificant moderating effect of the etiology indicates damage of dual pathways is the common neural mechanism, while sex and age influence the correlation with comprehension and naming ability, respectively, in specific tracts.

Characteristics and risk factors of deep vein thrombosis in hemiplegic, healthy and bilateral limbs of hemiplegic patients: a 10-year retrospective study.

Deep vein thrombosis (DVT) in hemiplegic patients mainly affects hemiplegic limbs, DVT can also occur only in healthy limbs, and some hemiplegic patients have DVT in both limbs. Characteristics and risk factors of DVT in hemiplegic, healthy, and bilateral limbs are unknown. To describe the proportion, risk factors, extent, and timing of DVT in hemiplegic, healthy and bilateral limbs. A 10-year retrospective review of consecutive patients was performed. DVT affected hemiplegic limbs in 34 (62%), healthy limbs in 11 (20%), and was bilateral in 10 (18%). DVT was more likely to develop in healthy limbs of hemiplegic patients without surgery (odds ratio (OR) 0.022; 95% confidence interval (CI) 0.001-0.922), and without diabetes (OR 0.023, 95% CI 0.001-0.853). Among the veins at the level of which DVT occurred, intermuscular veins represented 20 (45%) in hemiplegic, 5 (37%) in healthy, and 6 (74%) in bilateral limbs. The median time that DVT occurred after hemiplegia onset was 18 days (interquartile range [IQR] 9-79) in hemiplegic, 17 days (IQR 10-56) in healthy, and 21 days (IQR 8-27) in bilateral limbs. Early and effective prevention of DVT after surgery and optimal management of diabetes may reduce the risk of DVT in bilateral limbs. It's important to prevent proximal extension of calf vein DVT. DVT prophylaxis should be started early and continued for at least 3 weeks after hemiplegia onset.

Relationship between white matter integrity and post-traumatic cognitive deficits: a systematic review and meta-analysis.

OBJECTIVE: To investigate relationships between cognitive domains and white matter changes in different regions in patients with cognitive deficits after traumatic brain injury (TBI). METHODS: Databases including PubMed, Embase, Web of Science and CENTRAL were searched for studies published before 5 August 2017. Correlation coefficients between cognition and white matter integrity, measured by diffusion metrics, including fractional anisotropy (FA), were pooled from 49 studies including 1405 patients. The influence of demographic factors was assessed by meta-regression analysis. RESULTS: Significant pooled FA-executive correlations (p<0.001) were found across various regions, including the corpus callosum (CC) (r=0.42, 95% CI 0.30 to 0.54), superior longitudinal fasciculus (r=0.50, 95% CI 0.41 to 0.59) and internal capsule (IC) (r=0.49, 95% CI 0.37 to 0.61). The fornix (r=0.62, 95% CI 0.45 to 0.78) and cingulum (r=0.57, 95% CI 0.34 to 0.81) particularly correlated with memory (p<0.001). The CC and IC also showed significant relationships with attention and processing speed (p<0.001). Demographic factors had no influence overall, except that studies with a greater proportion of males had stronger correlations between memory and white matter (p<0.05). CONCLUSIONS: FA is the most sensitive metric for detecting post-TBI cognitive decline across various domains. Representative white matter regions, such as the CC and IC, perform better than whole-brain white matter for reflecting a wide range of cognitive domains, including memory, attention and executive functions. Moreover, the fornix and cingulum particularly reflect memory function. They yield insights into particular imaging indicators that have neuropsychological value.

Efficiency of Repetitive Transcranial Direct Current Stimulation of the Dorsolateral Prefrontal Cortex in Disorders of Consciousness: A Randomized Sham-Controlled Study.

Conventional transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex (DLPFC) could improve arousal in disorders of consciousness (DOC). However, the comparative effectiveness of anodal stimulation of the left DLPFC and the electrophysiological effect of tDCS are yet to be determined. In this randomized sham-controlled design, patients were separated into three groups (left/right anodal tDCS, sham). Data on the clinical assessments and EEG were collected at baseline and after 2 weeks of tDCS. The outcome at 3-month follow-up was evaluated using the Glasgow Outcome Scale-Extended. Results showed that sessions of the left tDCS facilitated the excitability of the prefrontal cortex, whereas only one patient had a positive outcome. Targeting the right DLPFC was less effective, merely leading to activation of the stimulation site, with no effect on the state of arousal. Moreover, sham stimulation had minimal or no effect on any of the outcomes. These results provide evidence for a hemispheric asymmetry of tDCS effects in patients with DOC. Left anodal tDCS might be more effective for modulating cortical excitability compared to tDCS on the right DLPFC. However, future studies with large sample sizes are needed to confirm these findings. This trial is registered with NCT03809936.

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).

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.

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].

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.

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).

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.

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.

The role of purinergic receptors in neural repair and regeneration after spinal cord injury.

Spinal cord injury is a serious injury of the central nervous system that results in neurological deficits. The pathophysiological mechanisms underlying spinal cord injury, as well as the mechanisms involved in neural repair and regeneration, are highly complex. Although there have been many studies on these mechanisms, there is no effective intervention for such injury. In spinal cord injury, neural repair and regeneration is an important part of improving neurological function after injury, although the low regenerative ability of nerve cells and the difficulty in axonal and myelin regeneration after spinal cord injury hamper functional recovery. Large amounts of ATP and its metabolites are released after spinal cord injury and participate in various aspects of functional regulation by acting on purinergic receptors which are widely expressed in the spinal cord. These processes mediate intracellular and extracellular signalling pathways to improve neural repair and regeneration after spinal cord injury. This article reviews research on the mechanistic roles of purinergic receptors in spinal cord injury, highlighting the potential role of purinergic receptors as interventional targets for neural repair and regeneration after spinal cord injury.

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.

Intracranial Myroides odoratimimus Infection After EVD Successfully Treated with Intravenous Plus Intraventricular Tigecycline: A Case Report.

Intracranial infections are the most serious and common postoperative complications with significant mortality and morbidity. Myroides odoratimimus (M. odoratimimus), a Gram-negative environmental species and an opportunistic microorganism, predominantly infects immunocompromised individuals. Limited clinical experiences and documented multidrug resistance have resulted in a scarcity of data on the treatment of M. odoratimimus infections. As far as we know, this is the first reported case of an intracranial M. odoratimimus infection with external ventricular drains (EVD) that was effectively treated with a combination of intravenous and intraventricular tigecycline in an immunocompetent adult host.