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.

[Intervention effect of Tuina pressing and kneading the Huantiao (GB30) acupoint on NF-κB p65 protein at spinal cord dorsal horn in sciatica rats].

OBJECTIVE: To observe the analgesic effect of Tuina by pressing and kneading the Huantiao (GB30) acupoint on rats with chronic constriction injury (CCI) and to explore the analgesic mechanism of Tuina on sciatica rats. METHODS: Thirty-two SPF male SD rats weighing 180 to 220 g were randomly divided into fore groups:blank group (without any treatment), sham group (only exposed without sciatic nerve ligating), model group (sciatic nerve ligating) and Tuina group (manual intervention after lsciatic nerve ligating). The CCI model was prepared by ligating the right sciatic nerve of the rats, on the third day of modeling, the rats in the Tuina group were given pressing and kneading the Huantiao (GB30) point for 14 days, and the changes of paw withdrawal threshold(PWT), paw withdrawal latency(PWL) were measured before and on the 1st, 3rd, 7th, 10th, 14th and 17th days after modeling. The changes of sciatic functional index(SFI) were measured before and on the 1st and 17th day after modeling. The morphological changes of the sciatic nerve were observed by hematoxylin-eosin(HE) staining;and the differences in NF-κB protein expression in the right dorsal horn of the spinal cord of rats were detected. RESULTS: Following modeling, there was no significant difference in PWT, PWL and SFI between the blank group and the sham group (P>0.05), but the PWT, PWL and SFI of the model group and the Tuina group decreased significantly (P<0.01). After manual intervention, the pain threshold of rats in Tuina group increased. On the 8th day of manual intervention (the 10th day after modeling), PWT in Tuina group increased significantly compared with that in model group (P<0.01). On the 5th day of manual intervention (the 7th day after modeling), the PWL of the massage group was significantly higher than that of the model group (P<0.01). The pain threshold of rats in Tuina group continued to rise with the continuous manipulation intervention. After 14 days of manipulative intervention, the sciatic nerve function index of rats in the Tuina group increased significantly(P<0.01). Compared with the blank group and sham group, the myelinated nerve fibers of sciatic nerve in the model group were disordered and the density of axons and myelin sheath was uneven. Compared with the model group, the nerve fibers of rats in the Tuina group were gradually continuous and the axons and myelin sheath were more uniform than those in the model group. Compared with the blank group and sham group, the expression of NF-κB protein in the right spinal dorsal horn of the model group was significantly increased(P<0.01). Compared with the model group, the expression of NF-κB protein in the right spinal dorsal horn of rats in Tuina group decreased significantly(P<0.01). CONCLUSION: Pressing and kneading the Huantiao (GB30) point restores nerve fiber alignment;and improves the PWT、PWL and SFI in the CCI model by decreasing NF-κB p65 protein expression in the spinal dorsal horn. There fore, Tuina demmstrates an analgesic effect and improves the gait of rats with sciatica.

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.

[Correlative analysis of cervical curvature and atlantoaxial instability].

OBJECTIVE: To investigate the correlation between the changes of cervical curvature and atlantoaxial instability. METHODS: The correlation between the changes of cervical curvature and atlantoaxial instability was retrospectively studied in 50 outpatients with abnormal cervical curvature (abnormal cervical curvature group) from January 2018 to December 2019. There were 24 males and 26 females in abnormal cervical curvature group, aged from 18 to 42 years old with an average of(30.62±5.83) years. And 53 patients with normal cervical curvature (normal cervical curvature group) during the same period were matched, including 23 males and 30 females, aged from 21 to 44 years with an average of(31.98±6.11) years. Cervical spine X-ray films of 103 patients were taken in lateral position and open mouth position. Cervical curvature and variance of bilateral lateral atlanto-dental space(VBLADS) were measured and recorded, Pearson correlation coefficient analysis was used to study the correlation between the changes of cervical curvature and atlantoaxial instability. RESULTS: Atlantoaxial joint instability accounted for 39.6%(21/53) in normal cervical curvature group and 84.0%(42/50) in abnormal cervical curvature group. There was significant difference between two groups(P<0.01). VBLADS in abnormal cervical curvature group was (1.79±1.01) mm, which was significantly higher than that in normal cervical curvature group(0.55±0.75) mm(P<0.01). Pearson correlation coefficient analysis showed that the size of cervical curvature was negatively correlated with VBLADS. CONCLUSION: Cervical curvature straightening and inverse arch are the cause of atlantoaxial instability, the smaller the cervical curvature, the more serious the atlantoaxial instability.