Efficacy of virtual reality exercise in knee osteoarthritis rehabilitation: a systematic review and meta-analysis.

Background: This systematic review and meta-analysis aims to investigate the effects of virtual reality (VR) exercise compared to traditional rehabilitation on pain, function, and muscle strength in patients with knee osteoarthritis (KOA). Additionally, the study explores the mechanisms by which VR exercise contributes to the rehabilitation of KOA patients. Methods: We systematically searched PubMed, the Cochrane Library, Embase, Web of Science, Scopus, and PEDro according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Our search spanned from the library construction to 24 May 2024, focusing on randomized controlled trials Primary outcomes included pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and muscle strength. Meta-analysis was conducted using RevMan (version 5.4) and Stata (version 14.0). The bias risk of included studies was assessed using the Cochrane RoB 2.0 tool, while the quality of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results: This meta-analysis and systematic review included nine studies involving 456 KOA patients. The results indicated that VR exercise significantly improved pain scores (SMD, -1.53; 95% CI: -2.50 to -0.55; p = 0.002), WOMAC total score (MD, -14.79; 95% CI: -28.26 to -1.33; p = 0.03), WOMAC pain score (MD, -0.93; 95% CI: -1.52 to -0.34; p = 0.002), knee extensor strength (SMD, 0.51; 95% CI: 0.14 to 0.87; p = 0.006), and knee flexor strength (SMD, 0.65; 95% CI: 0.28 to 1.01; p = 0.0005), but not significantly for WOMAC stiffness (MD, -0.01; 95% CI: -1.21 to 1.19; p = 0.99) and physical function (MD, -0.35; 95% CI: -0.79 to -0.09; p = 0.12). Conclusion: VR exercise significantly alleviates pain, enhances muscle strength and WOMAC total score in KOA patients, but improvements in joint stiffness and physical function are not significant. However, the current number of studies is limited, necessitating further research to expand on the present findings. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024540061, identifier CRD42024540061.

P2X7 receptors: a bibliometric review from 2002 to 2023.

For many years, there has been ongoing research on the P2X7 receptor (P2X7R). A comprehensive, systematic, and objective evaluation of the scientific output and status of P2X7R will be instrumental in guiding future research directions. This study aims to present the status and trends of P2X7R research from 2002 to 2023. Publications related to P2X7R were retrieved from the Web of Science Core Collection database. Quantitative analysis and visualization tools were Microsoft Excel, VOSviewer, and CiteSpace software. The analysis content included publication trends, literature co-citation, and keywords. 3282 records were included in total, with the majority of papers published within the last 10 years. Based on literature co-citation and keyword analysis, neuroinflammation, neuropathic pain, gastrointestinal diseases, tumor microenvironment, rheumatoid arthritis, age-related macular degeneration, and P2X7R antagonists were considered to be the hotspots and frontiers of P2X7R research. Researchers will get a more intuitive understanding of the status and trends of P2X7R research from this study.

[Effect of moxibustion on JAK2/STAT3 signal pathway in synovial tissues of rabbits with adjuvant arthritis under the overexpression of NLRP3 inflammatory bodies].

OBJECTIVE: To observe the effect of moxibustion on Janus protein tyrosine kinase 2/signal transducer and activator of transcription 3 (JAK2-STAT3) signal pathway and interleukin (IL)-1ß and IL-18 in synovial fluid of adjuvant arthritis (AA) rabbits, so as to explore the mechanism of moxibustion in the treatment of rheumatoid arthritis. METHODS: Twenty-eight rabbits were randomized into control, model, moxibustion, and NLRP3 overexpression groups, with 7 rabbits in each group. AA rabbit model was established by injection of Freund's complete adjuvant (FCA, 0.5 mL/kg) into the rabbits' bilateral hind-knee joint cavities. On the third day after modeling, the NLRP3 lentiviral vector (40 µL) were injected into the bilateral hind-knee joint cavities of rabbits in NLRP3 overexpression group. Moxibustion was used to bilateral "Shenshu" (BL23) and "Zusanli" (ST36), 5 cones every time, once daily, 6 days a week for 3 weeks in the moxibustion and NLRP3 overexpression groups. The perimeters of rabbits' hind legs were measured after modeling and after the intervention. The contents of IL-1ß, IL-18 in synovial fluid were detected by ELISA and the expression levels of NLRP3, JAK2 and STAT3 mRNAs in synovial tissue were detected by real-time PCR. RESULTS: In comparison with the control group, the perimeters of bilateral knee joints were significantly increased at each time point (P<0.05),and the contents of IL-1ß, IL-18 in synovial fluid and the expression levels of NLRP3, JAK2, STAT3 mRNA in synovial tissue were significantly increased (P<0.05) in the model group. Compared with the model group, the perimeters of bilateral knee joints were significantly decreased (P<0.05), and the contents of IL-1ß, IL-18 in synovial fluid and the expression levels of NLRP3, JAK2, STAT3 mRNAs in synovial tissue were significantly decreased (P<0.05) in the moxibusion group. Compared with the moxibustion group, the above indexes were higher in the NLRP3 overexpression group (P<0.05). CONCLUSION: Moxibustion may play an anti-inflammatory and detumescent role in AA rabbits by regulating JAK2-STAT3 signal pathway, and its therapeutic effect may be closely related to the expression of NLRP3.

Effect of chrono-moxibustion and its influence on circadian rhythm for rheumatoid arthritis: A study protocol for a randomized controlled trial.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic disease which is characterized by a circadian variation of key clinical symptoms and findings, with prominent joint swelling, stiffness and pain occurring in the early morning and light clinical symptoms during the day. Chrono-moxibustion is carried out at different time, which could result in dissimilar therapeutic effects. However, its efficacy has seldom been systematically demonstrated and few studies have reported that Chrono-moxibustion may regulate the circadian rhythm of RA. We therefore designed a randomized trial to explore the effective difference of Chrono-moxibustion in RA treatment, as well as to study its influence on circadian rhythm of RA patients. METHODS: This study is a randomized controlled trial involving 120 participants, and a total of 90 eligible RA patients will be randomly allocated to three groups in a 1:1:1 ratio as moxibustion at 7 to 9 am, moxibustion at 5 to 7 pm, and waiting list group, meanwhile, 30 healthy people will be divided into the control group. Patients in moxibustion groups will be treated for 30 minutes per session, 3 times a week, lasting 6 weeks. All of RA patients will be evaluated with questionnaires and laboratory tests before treatment, as well as 3 weeks, 6 weeks, and 3 months after treatment. One way analysis of variance (ANOVA) with multiple comparisons will be applied to identify differences more than two groups. Halberg cosiner software will be used to analysis the circadian rhythm. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: This study will provide evidence-based evidence for the effective difference of Chrono-moxibustion in RA treatment and its influence on circadian rhythm of RA patients.

Changes in glycaemic control of oral anti-diabetic medications assessed by continuous glucose monitors among patients with type 2 diabetes: a protocol of network meta-analysis.

BACKGROUND: Continuous glucose monitors (CGMs) can measure interstitial fluid glucose levels to provide comprehensive real-time glucose profile among people with type 2 diabetes. These can accurately detect glucose levels, hyperglycaemia and hypoglycaemia events compared with conventional self-monitoring. Increased application of CGMs provides a valuable opportunity to evaluate glucose control on oral anti-diabetic medications. This review will compare the efficacy and safety of oral anti-diabetic medications among patients with type 2 diabetes, evaluated by CGM. METHODS: The following databases will be searched: Cochrane Library, PubMed, EMBASE, CINAHL, PsycINFO, Scopus and grey literature (ClinicalTrials.gov, PsycEXTRA, ProQuest Dissertations, Google Scholar and Theses Global) for the identification of studies. The review will include and summarise evidence from randomised clinical trials that use CGMs for blood glucose management in adults (aged ≥ 18 years), published in English between January 2000 and May 2021 without any restrictions of countries. Reference list of all selected articles will independently be screened to identify additional studies left out in the initial search. Primary outcomes will be HbA1c (≤ 7.0%), time spent with hypoglycaemia (< 70 mg/dl) or hyperglycaemia (≥ 180 mg/dl). Secondary outcomes will be change in weight, blood pressure and related comorbidities (cardiovascular mortality, heart failure events, myocardial infarction and stroke). Study selection, data extraction and quality assessment will be conducted independently by at least two reviewers. A third reviewer will determine and resolve discrepancies. At least two independent reviewers will cross-check data synthesis. The quality of evidence of the review will be assessed according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Tool. DISCUSSION: The review is anticipated to provide up to date evidence for further studies and clinic practices regarding glycaemic control, hypoglycaemia, and hyperglycaemia issues. The results will be published in a peer-reviewed journal. TRIAL REGISTRATION: PROSPERO CRD42020188399 .

Barriers and facilitators of diabetes management by continuous glucose monitoring systems among adults with type 2 diabetes: a protocol of qualitative systematic review.

INTRODUCTION: Studies suggest that continuous glucose monitors (CGMs) play an important role in the management of diabetes. Although general acceptance has been reported by patients with type 2 diabetes towards the use of CGMs, potential barriers exist like pain due to sensor insertion, accidental removal of the device or adhesive strip, impacts of daily activities, skin reactions to sensor adhesive, etc. This systematic review of qualitative studies aims to explore the perspectives, experiences and narratives of patients and caregivers about CGM use, and its barriers and facilitators. METHODS AND ANALYSIS: This review will include qualitative studies and cross-sectional and longitudinal cohort studies using open-ended questions, published in English by 30 October 2021. The following electronic databases will be searched: Cochrane Library, PubMed, EMBASE, CINAHL, PsycINFO and Scopus. A search of grey literature will be conducted via an online search of Google Scholar, WorldCat, ClinicalTrials.gov and OpenGrey A combined search strategy using medical subject headings (MeSH), controlled vocabulary and 'free-text' terms will be appropriately revised to suit each database. Primary outcomes will include patient and caregiver perspectives on diabetes management regarding glucose control; living with CGM (quality of life, experience of wearing a CGM); psychological aspects (anxiety, depression, emotional burden); barriers (technical issues, financial issues) to use of CGM and thoughts (interpretation, understanding) on the CGM report. A qualitative meta-synthesis will be conducted employing a systematic literature search of existing literature, quality assessment using study-specific tools and an aggregative thematic synthesis by a multidisciplinary team. ETHICS AND DISSEMINATION: Ethical approval is not required since this is a systematic review. The results will help improve clinical implementation of CGMs on part of both patients and caregivers. PROSPERO REGISTRATION NUMBER: CRD42020152211.

Comparing effects of continuous glucose monitoring systems (CGMs) and self-monitoring of blood glucose (SMBG) amongst adults with type 2 diabetes mellitus: a systematic review protocol.

BACKGROUND: Continuous glucose monitorings (CGMs) have been used to manage diabetes with reasonable glucose control amongst patients with type 2 diabetes (T2D) in recent decades. CGMs measure interstitial fluid glucose levels to provide information about glucose levels, which identify fluctuation that would not have been identified with conventional self-monitoring. Self-monitoring of blood glucose (SMBG) is a classical tool to measure glycaemic changes. However, the effectiveness of glucose control, hypoglycemia, weight change, quality of life and user satisfaction, are needed to evaluate and compare CGMs and SMBG amongst adults with T2D. METHODS: The review will compare the various forms of CGM systems (i.e flash CGM, real-time CGM, retrospective CGM) versus SMBG or usual intervention regarding diabetes management amongst adults with T2D. The following databases will be searched: Cochrane Library, PubMed, EMBASE, CINAHL, PsycINFO, Scopus and grey literature (ClinicalTrials.gov, PsycEXTRA, ProQuest Dissertations, Google Scholar and Theses Global) for the identification of studies. The studies involving adults (aged ≥ 18 years old) will be included. We will only include and summarise randomised clinical trials (RCTs) with respect to authors, publication type, year, status and type of devices. Studies published in English between February 2010 and March 2020, will be included as the field of CGMs amongst T2D patients has emerged over the last decade. Primary outcomes will be HbA1c (glycosylated haemoglobin level) (mmol/L), body weight (kg), time spent with hypoglycaemia (< 70 mg/dl) or hyperglycaemia (≥ 180 mg/dl), blood pressure (< 140/90 mmHg is considered as good management) and quality of life (understanding and feeling of living situation based on culture and value system). Secondary outcome measures will be user satisfaction (patient or treatment/intervention satisfaction or satisfaction scale) and barriers (physical and mental difficulties or issues). Study selection, data extraction and risk of bias assessment will be conducted independently by at least two reviewers. A third reviewer will determine and resolve discrepancies. Moreover, the quality of the evidence of the review will be assessed according to the Grading of Recommendations Assessment, Development and Evaluation tool (GRADE). DISCUSSION: The review will synthesise evidence on the comparison between using CGMs and SMBG. The results will support researchers and health professionals to determine the most effective methods/technologies in the overall diabetes management. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020149212.

[Effects of moxibustion intervention on inflammatory reactions and expression of suppressor of cytokine signaling proteins of synovium cells in rheumatoid arthritis rabbits].

OBJECTIVE: To observe the effect of moxibustion intervention on inflammatory reactions and expression of suppressor of cyfokine signaling 1 (SOCS 1) and SOCS 2 [Which are involved in inhibition of the Janus Kinase-signal transducer and activator of transcrip-tion (JAK/STAT signaling pathway and in sffenuation of cytokine signaling)] in synovium cells of the hind-knee joint in rheumatoid arthritis (RA) rabbits, so as to study its mechanism underlying improvement of RA. METHODS: Forty-two Japanese big-ear white rabbits were randomized into control, model and moxibustion groups respectively, with 14 cases in each group. RA model was established by injection of Freund's Complete Adjuvant (0. 5 mL/kg) into the rabbits' bilateral hind-knee joint cavities. Moxibustion was applied to bilateral "Shenshu" (BL 23) areas, 5 cones every time, once daily for 3 weeks except the Sundays. The perimeters of rabbits' hind legs were measured before and after modeling and after the therapy. The synovial tissue of joint was sampled for analyzing the expression levels of SOCS 1 and SOCS 3 by immunohistochemistry. RESULTS: Before the therapy, the perimeters of bilateral knee joints of the control, model and moxibustion groups were of no statistical significance (P>0. 05). In comparison with the control group, the perimeters of bilateral knee joints were significantly increased on day 1, 7, 14 and 21 in the model group (P<0. 01). Compared with the model group, the perimeters of bilateral knee joints in the moxibustion group were significantly decreased (P<0. 05), suggesting an improvement of the inflammatory reaction after moxibustion intervention. Correspondingly, synovial SOCS 1 and SOCS 3 expression levels were remarkabely higher in the model group than in the control group (P<0. 01), and obviously decreased in the moxibustion group compared with the model group (P<0. 01). CONCLUSIONS: Moxibustion intervention has an anti-inflammatory and detumescent effects in RA rabbits, which may be closely associated with its effects in down-regulating expression of SOCS 1 and SOCS 3 proteins by suppressing negative feedback regulatory JAK/STAT pathway in synovial cells. [KEY WORDS] Moxibustion; Rheumatoid arthritis; Inflammatory reactions; Synovial cells; Suppressor of cytokine signaling proteins; Negative-feedback regulatory factors

[Effects of heat and cool-producing needling manipulations on rectal temperature and serum endotoxin content in endotoxin-induced heat syndrome rabbits].

OBJECTIVE: To observe the effect of traditional manipulations of "Shaoshanhuo" (heat-producing needling) and "Toutianliang"(cool-producing needling) on body temperature and serum endotoxin level in heat syndrome rabbits. METHODS: Twenty-four Japanese rabbits were randomly divided into control, model, Shaoshanhuo and Toutianliang groups. Heat-syndrome model was established by subcutaneous injection of bacterium coli endotoxin solution (40 microg/mL, 2 mL/kg). Heat-producing and cool-producing needling was applied to bilateral "Quchi" (LI 11) for 5 min, respectively. Rectal temperature was detected by using a thermometer, and serum endotoxin content assayed by using Limulus Ameboyte Lysate kit (luminescence measuring). RESULTS: In comparison with the control group, both rectal temperature and serum endotoxin levels were increased significantly in the model group (P < 0.01). While compared to the model group, the rectal temperature and serum endotoxin levels were down-regulated considerably in both Shaoshanhuo and Toutianliang groups (P < 0.05, P < 0.01). The effect of the Toutianliang group was obviously superior to that of the Shaoshanhuo group in reducing serum endotoxin content (P < 0.01). CONCLUSION: Both heat-producing needling and cool-producing needling can lower rectal temperature and serum endotoxin levels in heat-syndrome rabbits, and the effect of cool-producing needling is relatively better in reducing endotoxin content.

[Influence of moxibustion on JAK-STAT signal transduction pathways of synovial cells in rheumatoid arthritis rabbits].

OBJECTIVE: To observe the effect of moxibustion on Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway of synovial cells in rheumatoid arthritis (RA) rabbits for revealing the underlying mechanism of moxibustion in the treatment of RA. METHODS: A total of 30 rabbits (Japanese Big-ear White species) were randomized (stratified random) into control, model and moxibustion groups with 10 cases in each. RA model was established by injection of Freund's Complete Adjuvant (FCA, 0.5 mL/kg) into the animal's bilateral joint cavities. Moxibustion was applied to bilateral "Shenshu" (BL 23), 5 cones every time, once daily (except Sundays), 3 weeks altogether. The synovial tissue of joint was sampled for analyzing the expression of signal molecules associated with JAK-STAT pathway with gene chip and bioinformation analytical techniques. RESULTS: Compared with normal control group, the perimeters of both knee joints in model group increased significantly from the 3rd day to 21st day after injection of FCA (P < 0.01), while compared with model group, those in moxibustion group decreased considerably from the 6th day on (P < 0.05, 0.01). In comparison with control group, JAK-STAT pathway-associated genes with up-regulated expression in model group were C/EBP beta, CBP, CRP, GATA3, IFNAR1, IFNAR2, IFNGR2, IL-10Rb, INDO, SH2B, STAT3, STAT6, JAK3 and GP130, and those with down-regulated expression were A2M, MIG and IL-2Rr, suggesting an abnormal activation of JAK-STAT pathway; while in comparison with model group, the related gene up-regulated in moxibustion group in the expression was IL22R and those down-regulated were Cyclin D1, C/EBP beta, CRP, GATA3, IFNAR2, INDO, JAK2, JAK3, V-JUN, STAT3, STAT5, SH2B and OSM, showing that moxibustion had an apparent inhibitory effect on AR-induced abnormal activation of some genes as C/EBP beta, GATA3, IFNAR2, INDO, etc. CONCLUSION: Moxibustion can resist inflammation and eliminate swelling in RA rabbits, which may be closely with its effect in inhibiting abnormal activation of JAK-STAT pathway in synovial cells.