Genetically predicted causal effects of gut microbiota on spinal pain: a two-sample Mendelian randomization analysis.

Background: Observational studies have hinted at a correlation between the gut microbiota and spinal pain (SP). However, the impact of the gut microbiota on SP remains inconclusive. Methods: In this study, we employed a two-sample Mendelian randomization (MR) analysis to explore the causal relationship between the gut microbiota and SP, encompassing neck pain (NP), thoracic spine pain (TSP), low back pain (LBP), and back pain (BP). The compiled gut microbiota data originated from a genome-wide association study (GWAS) conducted by the MiBioGen consortium (n = 18,340). Summary data for NP were sourced from the UK Biobank, TSP from the FinnGen Biobank, and LBP from both the UK Biobank and FinnGen Biobank. Summary data for BP were obtained from the UK Biobank. The primary analytical approach for assessing causal relationships was the Inverse Variance Weighted (IVW) method, supplemented by various sensitivity analyses to ensure result robustness. Results: The IVW analysis unveiled 37 bacterial genera with a potential causal relationship to SP. After Benjamini-Hochberg corrected test, four bacterial genera emerged with a strong causal relationship to SP. Specifically, Oxalobacter (OR: 1.143, 95% CI 1.061-1.232, P = 0.0004) and Tyzzerella 3 (OR: 1.145, 95% CI 1.059-1.238, P = 0.0007) were identified as risk factors for LBP, while Ruminococcaceae UCG011 (OR: 0.859, 95% CI 0.791-0.932, P = 0.0003) was marked as a protective factor for LBP, and Olsenella (OR: 0.893, 95% CI 0.839-0.951, P = 0.0004) was recognized as a protective factor for low back pain or/and sciatica. No significant heterogeneity or horizontal pleiotropy was observed through alternative testing methods. Conclusion: This study establishes a causal relationship between the gut microbiota and SP, shedding light on the "gut-spine" axis. These findings offer novel perspectives for understanding the etiology of SP and provide a theoretical foundation for potential interventions targeting the gut microbiota to prevent and treat SP.

Intelligent structure prediction and visualization analysis of non-coding RNA in osteosarcoma research.

Background: Osteosarcoma (OS) is the most common bone malignant tumor in children and adolescents. Recent research indicates that non-coding RNAs (ncRNAs) have been associated with OS occurrence and development, with significant progress made in this field. However, there is no intelligent structure prediction and literature visualization analysis in this research field. From the perspective of intelligent knowledge structure construction and bibliometrics, this study will comprehensively review the role of countries, institutions, journals, authors, literature citation relationships and subject keywords in the field of ncRNAs in OS. Based on this analysis, we will systematically analyze the characteristics of the knowledge structure of ncRNAs in OS disease research and identify the current research hotspots and trends. Methods: The Web of Science Core Collection (WoSCC) database was searched for articles on ncRNAs in OS between 2001 and 2023. This bibliometric analysis was performed using VOSviewers, CiteSpace, and Pajek. Results: This study involved 15,631 authors from 2,631 institutions across 57 countries/regions, with a total of 3,642 papers published in 553 academic journals. China has the highest number of published papers in this research field. The main research institutions include Nanjing Medical University (n = 129, 3.54%), Shanghai Jiao Tong University (n = 128, 3.51%), Zhengzhou University (n = 110, 3.02%), and China Medical University (n = 109, 2.99%). Oncology Letters (n =139, 3.82%), European Review for Medical Pharmacological Sciences (120, 3.31%), and Molecular Medicine Reports (n = 95, 2.61%) are the most popular journals in this field, with Oncotarget being the most co-cited journal (Co-Citation = 4,268). Wei Wang, Wei Liu, and Zhenfeng Duan published the most papers, with Wang Y being the most co-cited author. "miRNA", "lncRNA" and "circRNA" are the main focuses of ncRNAs in OS studies. Key themes include "migration and invasion", "apoptosis and proliferation", "prognosis", "biomarkers" and "chemoresistance". Since 2020, hotspots and trends in ncRNA research in OS include "tumor microenvironment", "immune" and "exosome". Conclusion: This study represents the first comprehensive bibliometric analysis of the knowledge structure and development of ncRNAs in OS. These findings highlight current research hotspots and frontier directions, offering valuable insights for future studies on the role of ncRNAs in OS.

Gene association analysis to determine the causal relationship between immune cells and juvenile idiopathic arthritis.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is a type of chronic childhood arthritis with complex pathogenesis. Immunological studies have shown that JIA is an acquired self-inflammatory disease, involving a variety of immune cells, and it is also affected by genetic and environmental susceptibility. However, the precise causative relationship between the phenotype of immune cells and JIA remains unclear to date. The objective of our study is to approach this inquiry from a genetic perspective, employing a method of genetic association analysis to ascertain the causal relationship between immune phenotypes and the onset of JIA. METHODS: In this study, a two-sample Mendelian randomization (MR) analysis was used to select single nucleotide polymorphisms (SNPs) significantly associated with immune cells as instrumental variables to analyze the bidirectional causal relationship between 731 immune cells and JIA. There were four types of immune features (median fluorescence intensity (MFI), relative cellular (RC), absolute cellular (AC), and morphological parameters (MP)). Finally, the heterogeneity and horizontal reproducibility of the results were verified by sensitivity analysis, which ensured more robust results. RESULTS: We found that CD3 on CM CD8br was causally associated with JIA at the level of 0.05 significant difference (95% CI = 0.630 ~ 0.847, P = 3.33 × 10-5, PFDR = 0.024). At the significance level of 0.20, two immunophenotypes were causally associated with JIA, namely: HLA DR on CD14+ CD16- monocyte (95% CI = 0.633 ~ 0.884, P = 6.83 × 10-4, PFDR = 0.16) and HLA DR on CD14+ monocyte (95% CI = 0.627 ~ 0.882, P = 6.9 × 10-4, PFDR = 0.16). CONCLUSION: Our study assessed the causal effect of immune cells on JIA from a genetic perspective. These findings emphasize the complex and important role of immune cells in the pathogenesis of JIA and lay a foundation for further study of the pathogenesis of JIA.

Effects of breathing exercises on low back pain in clinical: A systematic review and meta-analysis.

OBJECTIVE: This study aims to systematically evaluate the effect of breathing exercises on the low back pain (LBP). METHODS: The studies of relevant randomized controlled trials (RCTs) testing the effect of breathing exercises on LBP were selected after strict screening from the establishment of PubMed, EMBASE, Cochrane Library, Web of Science, CBM, and CNKI databases until September 2022. The studies included were then independently assessed for risk bias by two investigators. The PRISMA 2020 statement was followed in this study. RESULTS: 11 RCTs involving 383 patients were included in this analysis. Results showed that the effective rate of LBP patients after breathing exercises was significantly higher than those in the control group, and the VAS (Visual Analogue Score) and ODI (Oswestry Disability Index) scores of LBP patients were significantly lower than those in the control group [VAS: MD = -0.50, 95% CI (-0.88, -0.11), I2 = 76%, p = 0.0009; ODI: MD = -2.46, 95% CI (-3.41, -1.52), I2 = 20%, p = 0.28]. The results of subgroup showed that the duration of treatment had little effect on the effect of breathing exercises, and breathing exercises alone could also have a positive effect on LBP. However, there were methodological limitations in the included studies, future studies should ensure blinded outcome assessors and full reporting to reduce bias risks. Because this review is a study of breathing exercises as an intervention without any adverse events, all studies did not involve safety assessments. CONCLUSIONS: The results indicated that breathing exercises have a positive effect on alleviating LBP, but due to the lack of methodological rigor and some limitations of the included studies, more critical RCTs are still needed in the future to verify the precision of this conclusion. The protocol was registered in PROSPERO (No. CRD42022345561).

Manual Therapy for a Chronic Non-Specific Low Back Pain Rat Model.

Chronic low back pain (CLBP) is a highly prevalent condition worldwide and a major cause of disability. The majority of patients with CLBP are diagnosed with chronic non-specific low back pain (CNLBP) due to an unknown pathological cause. Manual therapy (MT) is an integral aspect of traditional Chinese medicine and is recognized as Tuina in China. It involves techniques like bone-setting and muscle relaxation manipulation. Despite its clinical efficacy in treating CNLBP, the underlying mechanisms of MT remain unclear. In animal experiments aimed at investigating these mechanisms, one of the main challenges is achieving normative MT on CNLBP model rats. Improving the stability of finger strength is a key issue in MT. To address this technical limitation, a standardized procedure for MT on CNLBP model rats is presented in this study. This procedure significantly enhances the stability of MT with the hands and alleviates common problems associated with immobilizing rats during MT. The findings of this study are of reference value for future experimental investigations of MT.

Lever positioning manipulation alters real-time brain activity in patients with lumbar disc herniation: An amplitude of low-frequency fluctuation and regional homogeneity study.

INTRODUCTION: Lumbar disk herniation (LDH) is the preeminent disease of lever positioning manipulation (LPM), a complex disorder involving alterations in brain function. Resting-state functional magnetic resonance imaging (rs-fMRI) has the advantages of non-trauma, zero radiation, and high spatial resolution, which has become an effective means to study brain science in contemporary physical therapy. Furthermore, it can better elucidate the response characteristics of the brain region of LPM intervention in LDH. We utilized two data analysis methods, the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) of rs-fMRI, to assess the effects of LPM on real-time brain activity in patients with LDH. METHODS: Patients with LDH (Group 1, n = 21) and age-, gender- and education-matched healthy controls without LDH (Group 2, n = 21) were prospectively enrolled. Brain fMRI was performed for Group 1 at two-time points (TPs): before LPM (TP1) and after one LPM session (TP2). The healthy controls (Group 2) did not receive LPM and underwent only one fMRI scan. Participants in Group 1 completed clinical questionnaires assessing pain and functional disorders using a Visual Analog Scale and the Japanese Orthopaedic Association (JOA), respectively. Furthermore, we employed MNL90 (Montreal Neurological Institute) as a brain-specific template. RESULTS: Compared to the healthy controls (Group 2), the patients with LDH (Group 1) had significant variation in ALFF and ReHo values in brain activity. After the LPM session (TP2), Group 1 at TP1 also showed significant variation in ALFF and ReHo values in brain activity. In addition, the latter (TP2 vs TP1) showed more significant changes in brain regions than the former (Group 1 vs Group 2). The ALFF values were increased in the Frontal_Mid_R and decreased in the Precentral_L in Group 1 at TP2 compared with TP1. The Reho values were increased in the Frontal_Mid_R and decreased in the Precentral_L in Group 1 at TP2 compared with TP1. The ALFF values were increased in the Precuneus_R and decreased in the Frontal_Mid_Orb_L in Group 1 compared with Group 2. Only three brain areas with significant activity in Group 1 compared with Group 2: Frontal_Mid_Orb_L, Frontal_Sup_Orb_L, and Frontal_Mid_R. ALFF value in the Frontal_Mid_R at TP2 correlated positively with the change rates of JOA scores between TP1 and TP2 (P = 0.04, r = 0.319, R2 = 0.102). DISCUSSION: Patients with LDH showed abnormal brain ALFF and ReHo values, which were altered after LPM. The default mode network, prefrontal cortex, and primary somatosensory cortex regions could predict real-time brain activity for sensory and emotional pain management in patients with LDH after LPM.

Bibliometric Analysis of Functional Magnetic Resonance Imaging Studies on Manual Therapy Analgesia from 2002-2022.

Background: Research on the brain mechanisms underlying manual therapy (MT)-induced analgesia has been conducted worldwide. However, no bibliometric analysis has been performed on functional magnetic resonance imaging (fMRI) studies of MT analgesia. To provide a theoretical foundation for the practical application of MT analgesia, this study examined the current incarnation, hotspots, and frontiers of fMRI-based MT analgesia research over the previous 20 years. Methods: All publications were obtained from the Science Citation Index-Expanded (SCI-E) of Web of Science Core Collection (WOSCC). We used CiteSpace 6.1.R3 to analyze publications, authors, cited authors, countries, institutions, cited journals, references, and keywords. We also evaluated keyword co-occurrences and timelines, and citation bursts. The search was conducted from 2002-2022 and was completed within one day on October 7, 2022. Results: In total, 261 articles were retrieved. The total number of annual publications showed a fluctuating but overall increasing trend. Author B. Humphreys had the highest number of publications (eight articles) and J. E. Bialosky had the highest centrality (0.45). The United States of America (USA) was the country with the most publications (84 articles), accounting for 32.18% of all publications. Output institutions were mainly the University of Zurich, University of Switzerland, and the National University of Health Sciences of the USA. The Spine (118) and the Journal of Manipulative and Physiological Therapeutics (80) were most frequently cited. The four hot topics in fMRI studies on MT analgesia were "low back pain", "magnetic resonance imaging", "spinal manipulation", and "manual therapy." The frontier topics were "clinical impacts of pain disorders" and "cutting-edge technical capabilities offered by magnetic resonance imaging". Conclusion: fMRI studies of MT analgesia have potential applications. fMRI studies of MT analgesia have linked several brain areas, with the default mode network (DMN) garnering the most attention. Future research should include international collaboration and RCTs on this topic.

A systematic review and meta-analysis of randomized controlled trials of manipulative therapy for patients with chronic neck pain.

BACKGROUND: An increasing number of people suffer from chronic neck pain due to increased telecommuting. Manual therapy is considered a safe and less painful method and has been increasingly used to alleviate chronic neck pain. However, there is controversy about the effectiveness of manipulation therapy on chronic neck pain. Therefore, this systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to determine the effectiveness of manipulative therapy for chronic neck pain. METHODS: A search of the literature was conducted on seven databases (PubMed, Cochrane Center Register of Controlled Trials, Embase, Medline, CNKI, WanFang, and SinoMed) from the establishment of the databases to May 2022. This study included RCTs on chronic neck pain managed with manipulative therapy compared with sham, exercise, and other physical therapies. The retrieved records were independently reviewed by two researchers. Further, the methodological quality was evaluated using the PEDro scale. All statistical analyses were performed using RevMan V.5.3 software. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) assessment was used to evaluate the quality of the study results. RESULTS: Seventeen RCTs, including 1190 participants, were included in this meta-analysis. Manipulative therapy showed better results regarding pain intensity and neck disability than the control group. Manipulative therapy was shown to relieve pain intensity (SMD = -0.83; 95% confidence interval [CI] = [-1.04 to -0.62]; p < 0.0001) and neck disability (MD = -3.65; 95% CI = [-5.67 to - 1.62]; p = 0.004). However, the studies had high heterogeneity, which could be explained by the type and control interventions. In addition, there were no significant differences in adverse events between the intervention and the control groups. CONCLUSIONS: Manipulative therapy reduces the degree of chronic neck pain and neck disabilities.

Efficacy of traditional Chinese exercises in patients with post-COVID-19 chronic fatigue syndrome: A protocol for systematic review and meta-analysis.

BACKGROUND: Some patients develop long-term symptoms after Corona virus disease 2019 (COVID-19), and chronic fatigue syndrome (CFS) is one of the main symptoms. CFS is characterized by fatigue lasting for more than 6 months accompanied by sleep disorders, anxiety, and depression, which causes a certain degree of harm to both physiological and psychological aspects of the individual. Traditional Chinese exercises (TCEs) are an ancient Chinese therapy and has recently been reported to be effective for CFS. Therefore, we will conduct a systematic review and meta-analysis aiming to accurately evaluate the efficacy of TCEs on post-COVID-19 CFS and provide an alternative treatment for post-COVID-19 CFS. METHODS: Seven databases (PubMed, Ovid Embase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), and Wanfang) will be searched from establishment to August 2022, and we will only include randomized controlled trials of TCEs for post-COVID-19 CFS. Two reviews will independently include the research according to the inclusion and exclusion criteria. Review Manager 5.2 software will be used to analyze the accepted literature, and the relative risk ratio (RR) and 95% confidence interval (CI) will be used as effect indicators for the outcome indicator dichotomous variables. For continuous variables, weighted mean difference (MD) and 95% CI will be used as effect indicators. The heterogeneity test will be assessed using the I2 statistic and Q statistic. The PEDro scale was used to evaluate the methodological quality of the included studies. Subgroup analysis was performed according to different TCEs, age, gender, and duration of CFS. RESULTS: This systematic review and meta-analysis will evaluate the efficacy of TCEs in post-COVID-19 CFS. CONCLUSION: The results of this study will provide reliable evidence for the effects of TCEs for post-COVID-19 CFS on patients' fatigue, anxiety, depression, sleep, and quality of life.

Effectiveness and safety of acupuncture and moxibustion for chronic prostatitis: A protocol for an overview of systematic reviews and meta-analysis.

BACKGROUND: Chronic prostatitis (CP) refers to a disease characterized by local pain and discomfort, urination discomfort, and quality of life. Acupuncture (ACU) and moxibustion are widely used in the treatment of CP, and the curative effect is satisfactory. Several systematic reviews (SRs) and meta-analyzes have reported the effectiveness of ACU and moxibustion in treating patients with CP. However, the evidence is not systematically integrated. This overview aims to integrate and evaluate the reliability of these SRs and the evidence generated from the ACU and moxibustion for CP meta-analysis. METHODS: We will make a comprehensive retrieval in seven databases as following: Embase, Cochrane Library, Pubmed, Chinese databases SinoMed (previously called the Chinese Biomedical Database), Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wanfang Data (WF). The time is limited from the construction of the library to May 2021. We will use the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) tool to evaluate methodological quality. Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols (PRISMA-P) will be used in the report checklist to assess the quality of reports in the study. The GRADE will be used to evaluate the included SRs and meta-analysis. Our reviewers will conduct SRs, qualification evaluation, data extraction, methodological quality and evidence quality screening in pairs. The outcomes of interest include: NIH-Chronic Prostatitis Symptom Index (NIH-CPSI), effective rate, other CP symptom scales, EPS-WBC, and adverse events. Evidence will be combined based on patient subgroups and results where appropriate. RESULTS: The results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: INPLASY202150018. CONCLUSION: This overview will provide comprehensive evidence of ACU and moxibustion for patients with CP.