Positive feedback loop PU.1-IL9 in Th9 promotes rheumatoid arthritis development.

OBJECTIVES: T helper 9 (Th9) cells are recognised for their characteristic expression of the transcription factor PU.1 and production of interleukin-9 (IL-9), which has been implicated in various autoimmune diseases. However, its precise relationship with rheumatoid arthritis (RA) pathogenesis needs to be further clarified. METHODS: The expression levels of PU.1 and IL-9 in patients with RA were determined by ELISA, western blotting (WB) and immunohistochemical staining. PU.1-T cell-conditional knockout (KO) mice, IL-9 KO and IL-9R KO mice were used to establish collagen antibody-induced arthritis (CAIA), respectively. The inhibitor of PU.1 and IL-9 blocking antibody was used in collagen-induced arthritis (CIA). In an in vitro study, the effects of IL-9 were investigated using siRNAs and IL-9 recombinant proteins. Finally, the underlying mechanisms were further investigated by luciferase reporter analysis, WB and Chip-qPCR. RESULTS: The upregulation of IL-9 expression in patients with RA exhibited a positive correlation with clinical markers. Using CAIA and CIA model, we demonstrated that interventions targeting PU.1 and IL-9 substantially mitigated the inflammatory phenotype. Furthermore, in vitro assays provided the proinflammatory role of IL-9, particularly in the hyperactivation of macrophages and fibroblast-like synoviocytes. Mechanistically, we uncovered that PU.1 and IL-9 form a positive feedback loop in RA: (1) PU.1 directly binds to the IL-9 promoter, activating its transcription and (2) Th9-derived IL-9 induces PU.1 via the IL-9R-JAK1/STAT3 pathway. CONCLUSIONS: These results support that the PU.1-IL-9 axis forms a positive loop in Th9 dysregulation of RA. Targeting this signalling axis presents a potential target approach for treating RA.

Sex differences in dorsolateral prefrontal cortical and superior colliculus activities support the impact of alcohol use severity and sleep deficiency on two-back memory.

Background: Working memory refers to a process of temporary storage and manipulation of information to support planning, decision-making, and action. Frequently comorbid alcohol misuse and sleep deficiency have both been associated with working memory deficits. However, how alcohol misuse and sleep deficiency interact to impact working memory remains unclear. In this study, we aim to investigate the neural processes inter-relating alcohol misuse, sleep deficiency and working memory. Methods: We curated the Human Connectome Project (HCP) dataset and investigated the neural correlation of working memory in link with alcohol use severity and sleep deficiency in 991 young adults (521 women). The two were indexed by the first principal component (PC1) of principal component analysis of all drinking metrics and Pittsburgh Sleep Quality Index (PSQI) score, respectively. We processed the imaging data with published routines and evaluated the results with a corrected threshold. We used path model to characterize the inter-relationship between the clinical, behavioral, and neural measures, and explored sex differences in the findings. Results: In whole-brain regression, we identified ß estimates of dorsolateral prefrontal cortex response (DLPFC ß) to 2- vs. 0-back in correlation with PC1. The DLPFC showed higher activation in positive correlation with PC1 across men and women (r=0.16, P<0.001). Path analyses showed the model PC1 → DLPFC ß â†’ differences in reaction time (2- minus 0-back; RT2-0) of correct trials → differences in critical success index (2- minus 0-back; CSI2-0) with the best fit. In women alone, in addition to the DLPFC, a cluster in the superior colliculus (SC) showed a significant negative correlation with the PSQI score (r=-0.23, P<0.001), and the path model showed the inter-relationship of PC1, PSQI score, DLPFC and SC ß's, and CSI2-0 in women. Conclusions: Alcohol misuse may involve higher DLPFC activation in functional compensation, whereas, in women only, sleep deficiency affects 2-back memory by depressing SC activity. In women only, path model suggests inter-related impact of drinking severity and sleep deficiency on 2-back memory. These findings suggest potential sex differences in the impact of drinking and sleep problems on working memory that need to be further investigated.

Effects of scapular treatment on chronic neck pain: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Chronic neck pain (CNP) is a common public health problem that affects daily living activities and quality of life. There is biomechanical interdependence between the neck and scapula. Studies have shown that shoulder blade function might be related to chronic neck pain. We therefore evaluated the effects of scapular targeted therapy on neck pain and function in patients with CNP. METHODS: Databases, including MEDLINE (via PubMed), EMBASE (via Ovid), Ovid, Web of Science, and Scopus, were systematically searched for randomized controlled trials published in English investigating treatment of the scapula for CNP before July 16, 2023. RESULTS: A total of 313 participants were included from 8 RCTs. Compared with those in the control group, the intervention in the scapular treatment group exhibited greater improvement in pain intensity (standardized mean difference (SMD) = 2.55; 95% CI = 0.97 to 4.13; P = 0.002), with moderate evidence. Subgroup analysis for pain intensity revealed a significant difference between the sexes, with only the female population (SMD = 6.23, 95% CI = 4.80 to 7.65) showing better outcomes than those with both sexes (SMD = 1.07, 95% CI = 0.57 to 1.56) (p < 0.00001). However, moderate evidence demonstrated no improvement in neck disability after scapular treatment (SMD of 0.24[-0.14, 0.62] of Neck Disability Index or Northwick Park Neck Pain Questionnaire). No effect of scapular treatment was shown on the pressure pain threshold (PPT). The cervical range of motion (CROM) and electromyographic activity of neck muscles could not be conclusively evaluated due to limited support in the articles, and further study was needed. However, the patient's head forward posture appeared to be corrected after scapular treatment. CONCLUSION: Scapular therapy was beneficial for relieving pain intensity in patients with CNP, especially in women. Head forward posture might also be corrected with scapular therapy. However, scapular therapy may have no effect on the PPT or neck disability. However, whether scapular therapy could improve CROM and cervical muscle activation in patients with CNPs had not been determined and needed further study.

Efficacy and safety of transcranial direct current stimulation in the treatment of fibromyalgia: A systematic review and meta-analysis.

OBJECTIVES: To update a systematic review of the efficacy and safety of transcranial direct current stimulation (tDCS) for analgesia, for antidepressant effects, and to reduce the impact of fibromyalgia (FM), looking for optimal areas of stimulation. METHODS: We searched five databases to identify randomized controlled trials comparing active and sham tDCS for FM. The primary outcome was pain intensity, and secondary outcome measures included FM Impact Questionnaire (FIQ) and depression score. Meta-analysis was conducted using standardized mean difference (SMD). Subgroup analysis was performed to determine the effects of different regional stimulation, over the primary motor cortex (M1), dorsolateral prefrontal cortex (DLPFC), opercular-insular cortex (OIC), and occipital nerve (ON) regions. We analyzed the minimal clinically important difference (MCID) by the value of the mean difference (MD) for an 11-point scale for pain, the Beck Depressive Inventory-II (BDI-II), and the Fibromyalgia Impact Questionnaire (FIQ) score. We described the certainty of the evidence (COE) using the tool GRADE profile. RESULTS: Twenty studies were included in the analysis. Active tDCS had a positive effect on pain (SMD= -1.04; 95 % CI -1.38 to -0.69), depression (SMD= -0.46; 95 % CI -0.64 to -0.29), FIQ (SMD= -0.73; 95 % CI -1.09 to -0.36), COE is moderate. Only group M1 (SD=-1.57) and DLPFC (SD=-1.44) could achieve MCID for analgesia; For BDI-II, only group DLPFC (SD=-5.36) could achieve an MCID change. Adverse events were mild. CONCLUSION: tDCS is a safe intervention that relieves pain intensity, reduces depression, and reduces the impact of FM on life. Achieving an MCID is related to the stimulation site and the target symptom.

Abnormal white matter structural network topological property in patients with temporal lobe epilepsy.

BACKGROUND: Diffusion tensor imaging (DTI) studies have demonstrated white matter (WM) abnormalities in patients with temporal lobe epilepsy (TLE). However, alterations in the topological properties of the WM structural network in patients with TLE remain unclear. Graph theoretical analysis provides a new perspective for evaluating the connectivity of WM structural networks. METHODS: DTI was used to map the structural networks of 18 patients with TLE (10 males and 8 females) and 29 (17 males and 12 females) age- and gender-matched normal controls (NC). Graph theory was used to analyze the whole-brain networks and their topological properties between the two groups. Finally, partial correlation analyses were performed on the weighted network properties and clinical characteristics, namely, duration of epilepsy, verbal intelligence quotient (IQ), and performance IQ. RESULTS: Patients with TLE exhibited reduced global efficiency and increased characteristic path length. A total of 31 regions with nodal efficiency alterations were detected in the fractional anisotropy_ weighted network of the patients. Communication hubs, such as the middle temporal gyrus, right inferior temporal gyrus, left calcarine, and right superior parietal gyrus, were also differently distributed in the patients compared with the NC. Several node regions showed close relationships with duration of epilepsy, verbal IQ, and performance IQ. CONCLUSIONS: Our results demonstrate the disruption of the WM structural network in TLE patients. This study may contribute to the further understanding of the pathological mechanism of TLE.

Surveillance and Outcomes of Pediatric Hematopoietic Stem Cell Transplantation Recipients During the Recent COVID-19 Outbreak in China.

Background: The COVID-19 pandemic presents challenges for healthcare systems globally, especially in vulnerable populations such as pediatric hematopoietic stem cell transplant (HSCT) recipients. This study examines the clinical characteristics and outcomes of COVID-19 infection in pediatric HSCT recipients within one year post-HSCT. Methods: Retrospective analysis was conducted on data from 247 pediatric patients. None of them had received SARS-CoV-2 vaccination or had prior infection. SARS-CoV-2 infection was confirmed using RT-PCR testing. COVID-19 disease severity was categorized according to established guidelines. Demographic, clinical, laboratory, imaging and treatment data were collected. Results: The median age of the cohort was 7±3.7 years, with thalassemia major as the predominant underlying disease. Allogeneic HSCT was performed in the majority of cases, with haploidentical donors being the most common source of grafts. Nearly half of the patients developed COVID-19, with significantly higher infection rates observed in recipients over 100 days compared to recipients within 100 days post-HSCT (40.1% vs 21.7%, p<0.05, Fisher's Exact test). Fever (n=107, 43.2%) and cough (n=88, 35.6%) were the most common symptoms. While most patients had mild disease and did not require specific anti-viral treatment, a significant proportion required hospitalization (n=34, 13.8%). Various treatments were employed hospitalized patients, including Paxlovid (n=19, 55.9%), methylprednisolone (n=7, 20.6%), IL-6 antibody (n=2, 5.9%), mesenchymal stem cells (n=3, 8.8%), and exosomes nebulization therapy (n=2, 5.9%). Despite multidisciplinary approaches, one patient died from severe respiratory failure. However, overall survival of all patients remained high (99.53%; CI 96.72-99.93%), indicating favorable outcomes in pediatric HSCT recipients with COVID-19. Conclusion: This study provides insights into clinical features, therapeutic measures, and outcomes of pediatric HSCT recipients following COVID-19 infection in a large HSCT center in China. These findings contribute to our understanding of COVID-19 in this population and inform strategies to mitigate the impact the pandemic's impact on their care.

Corrigendum: Hydroxychloroquine attenuates autoimmune hepatitis by suppressing the interaction of GRK2 with PI3K in T lymphocytes.

[This corrects the article DOI: 10.3389/fphar.2022.972397.].

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OBJECTIVES: To explore the risk factors for hemorrhagic cystitis (HC) in children with ß-thalassemia major (TM) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A retrospective analysis was conducted on clinical data of 247 children with TM who underwent allo-HSCT at Shenzhen Children's Hospital from January 2021 to November 2022. The children were divided into an HC group (91 cases) and a non-HC group (156 cases) based on whether HC occurred after operation. Multivariable logistic regression analysis was used to explore the risk factors for HC, and the receiver operating characteristic curve was used to analyze the predictive efficacy of related factors for HC. RESULTS: Among the 247 TM patients who underwent allo-HSCT, the incidence of HC was 36.8% (91/247). Univariate analysis showed age, incompatible blood types between donors and recipients, occurrence of acute graft-versus-host disease (aGVHD), positive urine BK virus deoxyribonucleic acid (BKV-DNA), and ≥2 viral infections were associated with the development of HC after allo-HSCT (P<0.05). Multivariable analysis revealed that incompatible blood types between donors and recipients (OR=3.171, 95%CI: 1.538-6.539), occurrence of aGVHD (OR=2.581, 95%CI: 1.125-5.918), and positive urine BKV-DNA (OR=21.878, 95%CI: 9.633-49.687) were independent risk factors for HC in children with TM who underwent allo-HSCT. The receiver operating characteristic curve analysis showed that positive urine BKV-DNA alone or in combination with two other risk factors (occurrence of aGVHD, incompatible blood types between donors and recipients) had a certain accuracy in predicting the development of HC after allo-HSCT (area under the curve >0.8, P<0.05). CONCLUSIONS: Incompatible blood types between donors and recipients, occurrence of aGVHD, and positive urine BKV-DNA are risk factors for HC after allo-HSCT in children with TM. Regular monitoring of urine BKV-DNA has a positive significance for early diagnosis and treatment of HC.

The effectiveness and safety of botulinum toxin injections for the treatment of sialorrhea with Parkinson's disease: a systematic review and meta-analysis.

BACKGROUND: Botulinum toxin (BoNT) injection is an important adjunctive method to treat sialorrhea. The purpose of this systematic review was to analyze the effect and safety of BoNT injections in the intervention of sialorrhea with Parkinson's disease (PD). METHODS: We searched PubMed, Web Of Science (WOS), Scopus, Cochrane CENTRAL, and Embase from inception until April 2022. Randomized controlled trials or randomized crossover trials comparing BoNT with placebo in sialorrhea with PD were eligible. PRISMA guidelines were used to carry out the meta-analysis. The Drooling Severity Frequency Scale (DSFS) score and the number of adverse events (AEs) were the primary and secondary outcomes, respectively. Standardized mean differences (SMDs) and risk differences (RDs) are used to express continuous and categorical outcomes, respectively. Heterogeneity among these studies was evaluated using I2 tests. We used the GRADE tool to assess the certainty of evidence (COE). RESULTS: Eight articles involving 259 patients compared BoNT injections with a placebo for PD with sialorrhea. This meta-analysis showed a significant reduction in DSFS scores between BoNT injections and placebo (SMD=-0.98; 95% CI, -1.27 to 0.70, p<0.001; COE: high). This meta-analysis showed a significant difference in AEs between BoNT injections and placebo (RD=0.15; 95% CI, 0.05 to 0.24, p=0.002; COE: low). CONCLUSIONS: The pooled results suggest that BoNT injections have some effect on DSFS scores with sialorrhea caused by PD. There are also mild adverse events, which generally recover within a week or so. The results indicate that BoNT injection is one of the treatments for sialorrhea caused by PD, but we need to pay attention to adverse events. In addition, the follow-up time was extended to observe oral hygiene, ulceration or dental caries, and digestive function. TRIAL REGISTRATION: Our review protocol was registered on PROSPERO (42021288334).

Engineering multifunctional rhizosphere probiotics using consortia of Bacillus amyloliquefaciens transposon insertion mutants.

While bacterial diversity is beneficial for the functioning of rhizosphere microbiomes, multi-species bioinoculants often fail to promote plant growth. One potential reason for this is that competition between different species of inoculated consortia members creates conflicts for their survival and functioning. To circumvent this, we used transposon insertion mutagenesis to increase the functional diversity within Bacillus amyloliquefaciens bacterial species and tested if we could improve plant growth promotion by assembling consortia of highly clonal but phenotypically dissimilar mutants. While most insertion mutations were harmful, some significantly improved B. amyloliquefaciens plant growth promotion traits relative to the wild-type strain. Eight phenotypically distinct mutants were selected to test if their functioning could be improved by applying them as multifunctional consortia. We found that B. amyloliquefaciens consortium richness correlated positively with plant root colonization and protection from Ralstonia solanacearum phytopathogenic bacterium. Crucially, 8-mutant consortium consisting of phenotypically dissimilar mutants performed better than randomly assembled 8-mutant consortia, suggesting that improvements were likely driven by consortia multifunctionality instead of consortia richness. Together, our results suggest that increasing intra-species phenotypic diversity could be an effective way to improve probiotic consortium functioning and plant growth promotion in agricultural systems.

Magnetoencephalography-based approaches to epilepsy classification.

Epilepsy is a chronic central nervous system disorder characterized by recurrent seizures. Not only does epilepsy severely affect the daily life of the patient, but the risk of premature death in patients with epilepsy is three times higher than that of the normal population. Magnetoencephalography (MEG) is a non-invasive, high temporal and spatial resolution electrophysiological data that provides a valid basis for epilepsy diagnosis, and used in clinical practice to locate epileptic foci in patients with epilepsy. It has been shown that MEG helps to identify MRI-negative epilepsy, contributes to clinical decision-making in recurrent seizures after previous epilepsy surgery, that interictal MEG can provide additional localization information than scalp EEG, and complete excision of the stimulation area defined by the MEG has prognostic significance for postoperative seizure control. However, due to the complexity of the MEG signal, it is often difficult to identify subtle but critical changes in MEG through visual inspection, opening up an important area of research for biomedical engineers to investigate and implement intelligent algorithms for epilepsy recognition. At the same time, the use of manual markers requires significant time and labor costs, necessitating the development and use of computer-aided diagnosis (CAD) systems that use classifiers to automatically identify abnormal activity. In this review, we discuss in detail the results of applying various different feature extraction methods on MEG signals with different classifiers for epilepsy detection, subtype determination, and laterality classification. Finally, we also briefly look at the prospects of using MEG for epilepsy-assisted localization (spike detection, high-frequency oscillation detection) due to the unique advantages of MEG for functional area localization in epilepsy, and discuss the limitation of current research status and suggestions for future research. Overall, it is hoped that our review will facilitate the reader to quickly gain a general understanding of the problem of MEG-based epilepsy classification and provide ideas and directions for subsequent research.

Distinguishing Patients with MRI-Negative Temporal Lobe Epilepsy from Normal Controls Based on Individual Morphological Brain Network.

Temporal Lobe Epilepsy (TLE) is the most common subtype of focal epilepsy and the most refractory to drug treatment. Roughly 30% of patients do not have easily identifiable structural abnormalities. In other words, MRI-negative TLE has normal MRI scans on visual inspection. Thus, MRI-negative TLE is a diagnostic and therapeutic challenge. In this study, we investigate the cortical morphological brain network to identify MRI-negative TLE. The 210 cortical ROIs based on the Brainnetome atlas were used to define the network nodes. The least absolute shrinkage and selection operator (LASSO) algorithm and Pearson correlation methods were used to calculate the inter-regional morphometric features vector correlation respectively. As a result, two types of networks were constructed. The topological characteristics of networks were calculated by graph theory. Then after, a two-stage feature selection strategy, including a two-sample t-test and support vector machine-based recursive feature elimination (SVM-RFE), was performed in feature selection. Finally, classification with support vector machine (SVM) and leave-one-out cross-validation (LOOCV) was employed for the training and evaluation of the classifiers. The performance of two constructed brain networks was compared in MRI-negative TLE classification. The results indicated that the LASSO algorithm achieved better performance than the Pearson pairwise correlation method. The LASSO algorithm provides a robust method of individual morphological network construction for distinguishing patients with MRI-negative TLE from normal controls.

Differences in the Default Mode Network of Temporal Lobe Epilepsy Patients Detected by Hilbert-Huang Transform Based Dynamic Functional Connectivity.

Resting-state functional connectivity, constructed via functional magnetic resonance imaging, has become an essential tool for exploring brain functions. Aside from the methods focusing on the static state, investigating dynamic functional connectivity can better uncover the fundamental properties of brain networks. Hilbert-Huang transform (HHT) is a novel time-frequency technique that can adapt to both non-linear and non-stationary signals, which may be an effective tool for investigating dynamic functional connectivity. To perform the present study, we investigated time-frequency dynamic functional connectivity among 11 brain regions of the default mode network by first projecting the coherence into the time and frequency domains, and subsequently by identifying clusters in the time-frequency domain using k-means clustering. Experiments on 14 temporal lobe epilepsy (TLE) patients and 21 age and sex-matched healthy controls were performed. The results show that functional connections in the brain regions of the hippocampal formation, parahippocampal gyrus, and retrosplenial cortex (Rsp) were reduced in the TLE group. However, the connections in the brain regions of the posterior inferior parietal lobule, ventral medial prefrontal cortex, and the core subsystem could hardly be detected in TLE patients. The findings not only demonstrate the feasibility of utilizing HHT in dynamic functional connectivity for epilepsy research, but also indicate that TLE may cause damage to memory functions, disorders of processing self-related tasks, and impairment of constructing a mental scene.

Successful Treatment of Rare Pulmonary Coprinopsis cinerea Infection in a 17-Year-Old Female After Hematopoietic Stem Cell Transplantation: A Case Report.

Invasive fungal infections (IFIs) are among the most severe complications in recipients of hematopoietic stem cell transplantation (HSCT) recipients and in patients with hematological malignancies. An increasing number of uncommon fungal infections have been reported in this era of antifungal prophylaxis. Coprinopsis cinerea is a rare pathogen that causes opportunistic infections in the immunocompromised patients, including HSCT recipients and is associated with very high mortality rates. Herein, we present a successfully treated pediatric HSCT patient with breakthrough pulmonary IFI caused by Coprinopsis cinerea despite posaconazole, prophylaxis using multidisciplinary approaches.

Association between cadmium exposure and pulmonary function reduction: Potential mediating role of telomere attrition in chronic obstructive pulmonary disease patients.

BACKGROUND: Environmental cadmium (Cd) exposure is linked to pulmonary function injury in the general population. But, the association between blood Cd concentration and pulmonary function has not been investigated thoroughly in chronic obstructive pulmonary disease (COPD) patients, and the potential mechanisms are unclear. METHODS: All eligible 789 COPD patients were enrolled from Anhui COPD cohort. Blood specimens and clinical information were collected. Pulmonary function test was conducted. The subunit of telomerase, telomerase reverse transcriptase (TERT), was determined through enzyme linked immunosorbent assay (ELISA). Blood Cd was measured via inductively coupled-mass spectrometer (ICP-MS). RESULTS: Blood Cd was negatively and dose-dependently associated with pulmonary function. Each 1-unit increase of blood Cd was associated with 0.861 L decline in FVC, 0.648 L decline in FEV1, 5.938 % decline in FEV1/FVC %, and 22.098 % decline in FEV1 % among COPD patients, respectively. Age, current-smoking, self-cooking and higher smoking amount aggravated Cd-evoked pulmonary function decrease. Additionally, there was an inversely dose-response association between Cd concentration and TERT in COPD patients. Elevated TERT obviously mediated 29.53 %, 37.50 % and 19.48 % of Cd-evoked FVC, FEV1, and FEV1 % declines in COPD patients, respectively. CONCLUSION: Blood Cd concentration is strongly associated with the decline of pulmonary function and telomerase activity among COPD patients. Telomere attrition partially mediates Cd-induced pulmonary function decline, suggesting an underlying mechanistic role of telomere attrition in pulmonary function decline from Cd exposure in COPD patients.

The role of transforming growth factor ß1 /Smad pathway in Alzheimer's disease inflammation pathology.

Alzheimer's disease (AD), a progressive disorder, has become a global health problem and is now the main cause of dementia. The aetiology of AD is complex and remains elusive making effective AD treatment difficult. Current drugs for AD only improve symptoms but do not interfere with pathogenic mechanisms. Three main hypotheses have been brought forward regarding AD aetiology, one of them being the 'inflammation hypothesis'. A number of studies have demonstrated that inflammation plays a critical role in AD. Self-limiting neuroinflammation is considered beneficial to AD, whereas chronic inflammation aggravates brain injury and neuronal death. Transforming growth factor ß 1(TGF-ß1) is an anti-inflammatory cytokine with neuroprotective properties. Smad proteins are downstream molecules of TGF-ß signalling. They are cytoplasmic transcription factors that can regulate targeted gene expression. In AD, impairments of TGF-ß1/Smad pathways have been observed. Moreover, microglia, astrocytes, inflammasomes, and insulin resistance also have been implicated in AD pathogenesis. Elucidating the molecular mechanisms underlying AD pathogenesis is a fundamental step toward designing new treatment options. In this review, we detail the changes in TGF-ß1/Smad pathways in AD and hope this will facilitate further research on AD treatment.

Comparative Efficacy of Neuromodulation Technologies for Overactive Bladder in Adults: A Network Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: The aim of this study was to investigate the comparative efficacy of neuromodulation technologies for overactive bladder (OAB) syndrome in adults. DATA SOURCES: A computerized search was conducted of Cochrane Library, EMBASE, MEDLINE (via PubMed), Web of Science, CNKI, Wan Fang Data, and ClinicalTrials.gov up to April 21, 2022. STUDY SELECTION: The search selected clinical trials with random allocation to percutaneous tibial nerve stimulation (PTNS), transcutaneous tibial nerve stimulation (TTNS), vaginal electrical stimulation (VES), sacral neuromodulation (SNM), parasacral stimulation (PS), pudendal neuromodulation, or placebo. DATA EXTRACTION: The main outcomes were the voiding diary, OAB-related quality of life, and positive response rate. The Cochrane Risk of Bias tool (RoB 2.0) was used to assess the risk of bias of each included study, and the Grading of Recommendations Assessment, Development, and Evaluation tool was used to evaluate the overall evidence quality of key outcomes. DATA SYNTHESIS: The study included 21 randomized controlled trials involving 1433 participants, and all trials were used for the meta-analysis. In the network meta-analyses, five of six neuromodulation technologies, including PTNS, TTNS, VES, SNM, and PS, were related to higher efficacy than the placebo. Ranking probability showed that SNM was the most efficacious therapy for improving OAB-related quality of life, urinary episodes, and urinary frequency. For urgency incontinence episodes and the number of pads, PTNS and TTNS were the most efficacious modalities, respectively. CONCLUSION: Neuromodulation technologies, including PTNS, TTNS, VES, SNM, and PS, may be effective and safe solutions for OAB syndrome in adults. Moreover, SNM is the most efficacious regimen for OAB-related quality of life, urinary episodes, and urinary frequency. PTNS and TTNS are the most efficacious modalities for reducing urgency incontinence episodes and the number of pads, respectively. Future studies should pay more attention to the quality of study design and report, patients who may benefit the most from neuromodulation, and the long-term effect, cost-effectiveness, and satisfaction of neuromodulation.

Effects and parameters of community-based exercise on motor symptoms in Parkinson's disease: a meta-analysis.

BACKGROUND: Community-based exercise is a continuation and complement to inpatient rehabilitation for Parkinson's disease and does not require a professional physical therapist or equipment. The effects, parameters, and forms of each exercise are diverse, and the effect is affected by many factors. A meta-analysis was conducted to determine the effect and the best parameters for improving motor symptoms and to explore the possible factors affecting the effect of community-based exercise.  METHODS: We conducted a comprehensive search of six databases: PEDro, PubMed/Medline, CENTRAL, Scopus, Embase, and WOS. Studies that compared community-based exercise with usual care were included. The intervention mainly included dance, Chinese martial arts, Nordic walking, and home-based exercise. The primary outcome measure was the Unified Parkinson's Disease Rating Scale part III (UPDRS-III) score. The mean difference (95% CI) was used to calculate the treatment outcomes of continuous outcome variables, and the I2 statistic was used to estimate the heterogeneity of the statistical analysis. We conducted subgroup analysis and meta-regression analysis to determine the optimal parameters and the most important influencing factors of the exercise effect.  RESULTS: Twenty-two studies that enrolled a total of 809 subjects were included in the analysis. Exercise had a positive effect on the UPDRS-III (MD = -5.83; 95% CI, -8.29 to -3.37), Timed Up and Go test (MD = -2.22; 95% CI -3.02 to -1.42), UPDRS ((MD = -7.80; 95% CI -10.98 to -6.42), 6-Minute Walk Test (MD = 68.81; 95% CI, 32.14 to 105.48), and Berg Balance Scale (MD = 4.52; 95% CI, 2.72 to 5.78) scores. However, the heterogeneity of each included study was obvious. Weekly frequency, age, and duration of treatment were all factors that potentially influenced the effect. CONCLUSIONS: This meta-analysis suggests that community-based exercise may benefit motor function in patients with PD. The most commonly used modalities of exercise were tango and tai chi, and the most common prescription was 60 min twice a week. Future studies should consider the influence of age, duration of treatment, and weekly frequency on the effect of exercise. PROSPERO TRIAL REGISTRATION NUMBER: CRD42022327162.

Cognitive function and brain activation before and after transcutaneous cervical vagus nerve stimulation in healthy adults: A concurrent tcVNS-fMRI study.

Transcutaneous vagus nerve stimulation, which involves the application of electrical currents to the cervical (tcVNS) or auricular (taVNS) branches of the vagus nerve, may be a potential treatment for improving cognitive dysfunction. taVNS may improve cognitive performance in healthy adults, and fewer studies have been performed on the effects of tcVNS on cognition in healthy subjects. We conducted a randomized, single-blind, crossover-controlled trial to investigate the effects of tcVNS stimulation on cognitive function and neural activity in the brains of healthy adults. This study provides support for further tcVNS studies for the treatment of cognitive impairment. Twenty-one participants were randomly divided into two groups, A and B. Group A received tcVNS first and then sham-tcVNS, while group B received the intervention in the reverse order, receiving sham stimulation first and then true stimulation. All subjects were required to perform cognitive function tests before and after receiving intervention, and functional magnetic resonance imaging (fMRI) was performed concurrently during the intervention. We hypothesized that tcVNS would have an effect on the cognitive performance of the subjects and alter the neural activity of the brain. The present study showed that tcVNS had beneficial effects on cognitive performance, mainly improving memory and language skills and attention. tcVNS intervention produced significant spontaneous neural activity in the calcarine gyrus, fusiform gyrus, lingual gyrus, and parahippocampal gyrus of the brain. Future tcVNS/fMRI trials will need to explore the effects of changes in stimulus parameters on the neural activity response of the brain.

Tumor Necrosis Factor: What Is in a Name?

Tumor Necrosis Factor was one of the first cytokines described in the literature as a soluble mediator of cytotoxicity to tumors. Over the years, more extensive research that tried to employ Tumor Necrosis Factor in cancer treatments showed nevertheless that it mainly functioned as a proinflammatory cytokine. However, this did not stop the search for the holy grail of cancer research: A cytokine that could act as a one-stop treatment for solid tumors and lymphomas. This review will summarize the long experimental history of Tumor Necrosis Factor that caused the initial observations of a tumor necrotizing cytokine that could serve as a potential cancer treatment and discuss the current state of research into this side of the activities of Tumor Necrosis Factor.