The causal relationship between human brain morphometry and knee osteoarthritis: a two-sample Mendelian randomization study.

Background: Knee Osteoarthritis (KOA) is a prevalent and debilitating condition affecting millions worldwide, yet its underlying etiology remains poorly understood. Recent advances in neuroimaging and genetic methodologies offer new avenues to explore the potential neuropsychological contributions to KOA. This study aims to investigate the causal relationships between brain-wide morphometric variations and KOA using a genetic epidemiology approach. Method: Leveraging data from 36,778 UK Biobank participants for human brain morphometry and 487,411 UK Biobank participants for KOA, this research employed a two-sample Mendelian Randomization (TSMR) approach to explore the causal effects of 83 brain-wide volumes on KOA. The primary method of analysis was the Inverse Variance Weighted (IVW) and Wald Ratio (WR) method, complemented by MR Egger and IVW methods for heterogeneity and pleiotropy assessments. A significance threshold of p < 0.05 was set to determine causality. The analysis results were assessed for heterogeneity using the MR Egger and IVW methods. Brain-wide volumes with Q_pval < 0.05 were considered indicative of heterogeneity. The MR Egger method was employed to evaluate the pleiotropy of the analysis results, with brain-wide volumes having a p-value < 0.05 considered suggestive of pleiotropy. Results: Our findings revealed significant causal associations between KOA and eight brain-wide volumes: Left parahippocampal volume, Right posterior cingulate volume, Left transverse temporal volume, Left caudal anterior cingulate volume, Right paracentral volume, Left paracentral volume, Right lateral orbitofrontal volume, and Left superior temporal volume. These associations remained robust after tests for heterogeneity and pleiotropy, underscoring their potential role in the pathogenesis of KOA. Conclusion: This study provides novel evidence of the causal relationships between specific brain morphometries and KOA, suggesting that neuroanatomical variations might contribute to the risk and development of KOA. These findings pave the way for further research into the neurobiological mechanisms underlying KOA and may eventually lead to the development of new intervention strategies targeting these neuropsychological pathways.

Non-pharmaceutical interventions for depressive symptoms in patients with breast cancer: protocol for a systematic review and network meta-analysis.

INTRODUCTION: Patients with breast cancer often suffer from depressive symptoms throughout various stages of cancer, significantly impacting their quality of life and treatment outcomes. Non-pharmaceutical interventions such as psychotherapy, mind-body therapies and physical exercise have shown effectiveness in addressing cancer-related depression. However, the efficacy and safety of different non-pharmacological interventions remain a topic of debate. Therefore, to provide an objective assessment and comparison of the impact of different non-pharmaceutical interventions on depression, we will conduct a network meta-analysis (NMA) to explore the effects of different non-pharmaceutical interventions on reducing depressive symptoms among patients with breast cancer. METHODS AND ANALYSIS: We will search nine Chinese and English-language databases, from database inception to 31 July 2023, for randomised controlled trials published in Chinese or English. The English-language databases are PubMed, Medline, Embase, Web of Science and Cochrane Central Register of Controlled Trials, and the Chinese databases are CBM, CNKI, VIP and Wanfang. Two independent researchers will perform information extraction from eligible articles. The primary outcome will be the changes in depressive symptoms, while the secondary outcome will include adverse events. STATA V.15.0 will be used to conduct paired meta-analysis and NMA. Grading of Recommendations Assessment, Development and Evaluation will be used to assess the quality of evidence, and the Cochrane tool for assessing the risks of bias in randomised trials V.2 will be used for risk of bias assessment. ETHICS AND DISSEMINATION: The study does not require ethical approval as it will analyse data from existing studies. It is expected that the results of the study will be published in peer-reviewed journals and presented at relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42023450494.

Continuous infusion of lidocaine in pediatric colonoscopy: A randomized double-blind placebo-controlled study.

BACKGROUND: Propofol is commonly used for providing procedural sedation during pediatric colonoscopy. Intravenous (i.v.) lidocaine can mitigate visceral pain and reduce propofol requirements during surgery. The aim of this study is to investigate the effect of i.v. lidocaine on perioperative propofol and sufentanil dose, pulse oxygen saturation, postoperative pain score, and recovery time during pediatric colonoscopy. METHODS: We designed a randomized, double-blind, placebo-controlled study and enrolled 40 children aged from 3 to 10 years who underwent colonoscopy. After titration of propofol to achieve unconsciousness, the patients were given i.v. lidocaine (1.5 mg/kg later 2 mg/kg/hour) or the same volume of saline. Sedation was standardized and combined propofol with sufentanil. The primary outcome variables were intraoperative propofol and sufentanil requirements, and the number of oxygen desaturation episodes. Secondary outcome variables were recovery time after colonoscopy and post-colonoscopy pain. RESULTS: Lidocaine infusion resulted in a significant reduction in propofol requirements: (median (quartile) 1.8 (1.5-2.0) vs. 3.0 (2.8-3.3) mg/kg respectively; P < 0.001) and sufentanil requirements: (median (quartile) 0.06 (0.05-0.08) vs. 0.1 (0.1-0.1) µg/kg respectively; P < 0.001). The number of subjects who experienced oxygen desaturation below 95% in the lidocaine group was also significantly less than that in the control group: 1 vs. 6 (P = 0.04). The mean (SD) recovery time was significantly shorter in the lidocaine group: (19.2 (2.6) vs. 13.3 (2.6) min respectively; P < 0.001). There was no significant difference in post-colonoscopy pain. CONCLUSION: Continuous infusion of lidocaine resulted in reduction of propofol and sufentanil requirements, recovery time, and risk of hypoxemia during pediatric colonoscopy.

Efficacy and safety of Shi-style cervical manipulation therapy for treating acute and subacute neck pain: study protocol for a randomized controlled trial.

BACKGROUND: Neck pain is a common clinical disease, which seriously affects people's mental health and quality of life and results in loss of social productivity. Improving neck pain's curative effect and reducing its recurrence rate are major medical problems. Shi's manipulation therapy has unique advantages and technical features that aid in the diagnosis and treatment of neck pain. Compared with first-line non-steroidal anti-inflammatory drug (NSAID) treatment of neck pain, Shi's cervical manipulation lacks the relevant research basis of therapeutic advantage, safety, and satisfaction for treating acute and subacute neck pain. Herein, we aim to confirm our hypothesis in a clinical trial that the safety and efficacy of Shi's cervical manipulation will be more effective, safer, and more satisfactory than NSAIDs to treat acute and subacute neck pain. METHODS: In this multicenter, positive-controlled, randomized clinical trial, traditional analgesic drug (NSAID) is used to evaluate and show that Shi's manipulation is more effective, safe, and satisfactory for treating acute and subacute neck pain. Overall, 240 subjects are randomly divided into the trial and control groups, with both groups treated by the corresponding main intervention method for up to 12 weeks. Clinical data will be collected before the intervention and immediately after the first treatment; at 3 days and 1, 2, 4, 8, and 12 weeks after the intervention; and at 26 and 52 weeks after treatment follow-up of clinical observation index data collection. The clinical observation indices are as follows: (1) cervical pain is the primary observation index, measured by Numerical Rating Scale. The secondary indices include the following: (2) cervical dysfunction index, measured by patient self-evaluation using cervical Neck Disability Index; (3) cervical activity measurement, measured by the cervical vertebra mobility measurement program of Android mobile phone system; (4) overall improvement, measured by patient self-evaluation with SF-36; and (5) satisfactory treatment, determined by patient self-evaluation. DISCUSSION: We will discuss whether Shi's cervical manipulation has greater advantages in efficacy, safety, and satisfaction of acute and subacute neck pain than traditional NSAIDs, to provide a scientific basis for the dissemination and application of Shi's cervical manipulation. TRIAL REGISTRATION: China Registered Clinical Trial Registration Center ChiCTR1900021371 . Registered on 17 February 2019.

Metabonomic-Transcriptome Integration Analysis on Osteoarthritis and Rheumatoid Arthritis.

PURPOSE: This study is aimed at exploring the potential metabolite/gene biomarkers, as well as the differences between the molecular mechanisms, of osteoarthritis (OA) and rheumatoid arthritis (RA). METHODS: Transcriptome dataset GSE100786 was downloaded to explore the differentially expressed genes (DEGs) between OA samples and RA samples. Meanwhile, metabolomic dataset MTBLS564 was downloaded and preprocessed to obtain metabolites. Then, the principal component analysis (PCA) and linear models were used to reveal DEG-metabolite relations. Finally, metabolic pathway enrichment analysis was performed to investigate the differences between the molecular mechanisms of OA and RA. RESULTS: A total of 976 DEGs and 171 metabolites were explored between OA samples and RA samples. The PCA and linear module analysis investigated 186 DEG-metabolite interactions including Glycogenin 1- (GYG1-) asparagine_54, hedgehog acyltransferase- (HHAT-) glucose_70, and TNF receptor-associated factor 3- (TRAF3-) acetoacetate_35. Finally, the KEGG pathway analysis showed that these metabolites were mainly enriched in pathways like gap junction, phagosome, NF-kappa B, and IL-17 pathway. CONCLUSIONS: Genes such as HHAT, GYG1, and TRAF3, as well as metabolites including glucose, asparagine, and acetoacetate, might be implicated in the pathogenesis of OA and RA. Metabolites like ethanol and tyrosine might participate differentially in OA and RA progression via the gap junction pathway and phagosome pathway, respectively. TRAF3-acetoacetate interaction may be involved in regulating inflammation in OA and RA by the NF-kappa B and IL-17 pathway.

Suppression of Development of Ankylosing Spondylitis Through Soluble Flt-1.

BACKGROUND/AIMS: Circulating monocytes/macrophages are origins of osteoclasts that mediate the development of ankylosing spondylitis (AS). Moreover, infiltrated macrophages facilitate the AS progression through production and secretion of pro-inflammatory cytokines. Thus, suppression of the recruitment of circulating monocytes/macrophages may be an effective AS treatment, which is, however, not available so far in clinic. Soluble fms-like tyrosine kinase-1 (sFlt-1) is a decoy receptor for vascular endothelial growth factor (VEGF) to compete with VEGF receptor (VEGFR2) for VEGF binding in endothelial cells, while its application in treating AS and effects on the recruitment of circulating monocytes/macrophages has not been reported before. METHODS: We used a proteoglycan-induced arthritis (PGIA) mouse model for human AS. We injected sFlt-1 into the articular cavity and evaluated its effects on PGIA by incidence of arthritis, and clinical and pathological arthritis severity. We isolated and analyzed macrophages and endothelial cells in the articular cavity before and after treatment. RESULTS: Injection of sFlt-1 significantly decreased the incidence and severity of PGIA in mice, and significantly reduced the number of infiltrated macrophages, possibly through reduction of vessel permeability, in a VEGFR2-dependent manner. CONCLUSION: Our data suggest that sFlt-1 may have a therapeutic effect on AS, resulting from suppression of VEGF signaling-mediated recruitment of circulating monocytes/macrophages.

Influence of pain severity on health-related quality of life in Chinese knee osteoarthritis patients.

OBJECTIVE: The aim of this cross-sectional study was to examine the relationship among pain and other symptoms intensity, and health-related quality of life (HRQoL) in Chinese patients with knee osteoarthritis (OA). METHODS: The study was cross-sectional, descriptive, and correlational. A convenience sample of 466 patients with knee OA was recruited in the study. Age, gender, body mass index (BMI), duration of disease, and Kellgren- Lawrence (KL) scores were recorded. HRQoL and symptoms were assessed using the 36-item Short Form Health Survey (SF-36) and the Western Ontario and McMaster (WOMAC) index in participants. RESULTS: The sample was predominantly female (82%) with mean age 56.56 years and mean BMI 24.53 kg/m(2). We found that WOMAC subscale scores significantly negative correlated with the majority of SF-36 subscale scores in knee OA patients (P < 0.05). There were no correlations between BMI, duration of disease, KL score and the vast majority of SF-36 subscale scores in patients (P > 0.05). In addition, there was a significant correlation between age and PCS, gender and MCS in patients (P < 0.05). Regression analysis showed, WOMAC subscale scores significantly negative correlated with the vast majority of SF-36 subscale scores. WOMAC-pain score had the strongest relationship with SF-36 PCS and MCS scores. CONCLUSIONS: In summary, pain severity has a greater impact on HRQoL than patient characteristics, other joint symptoms and radiographic severity in Chinese knee OA patients. Relieving of knee symptoms may help to improve patients' HRQOL. The study provided the evidence that relieving pain should be the first choice of therapy for knee osteoarthritis.

Overexpression of miR-506 inhibits growth of osteosarcoma through Snail2.

Osteosarcoma (OS) is a prevalent primary bone malignancy and its distal metastasis accounts for the majority of OS-related death. MicroRNAs (miRNAs) play critical roles during cancer metastasis. Thus, elucidation of the involvement of specific miRNAs in the metastasis of OS may provide novel therapeutic targets for OS treatment. Here, we showed that in the OS specimens from patients, the levels of miR-506 were significantly decreased and the levels of Snail2 were significantly increased, compared to the paired normal bone tissue. MiR-506 and Snail2 inversely correlated in patients' specimen. Bioinformatics analyses predicted that miR-506 may target the 3'-UTR of Snail2 mRNA to inhibit its translation, which was confirmed by luciferase-reporter assay. Moreover, miR-506 overexpression inhibited Snail2-mediated cell invasiveness, while miR-506 depletion increased Snail2-mediated cell invasiveness in OS cells. Together, our data suggest that miR-506 suppression in OS cells may promote Snail2-mediated cancer metastasis.

Glucan HBP-A increase type II collagen expression of chondrocytes in vitro and tissue engineered cartilage in vivo.

OBJECTIVE: Although chondroprotective activities have been documented for polysaccharides, the potential target of different polysaccharide may differ. The study was aimed to explore the effect of glucan HBP-A in chondrocyte monolayer culture and chondrocytes-alginate hydrogel constructs in vivo, especially on the expression of type II collagen. METHODS: Chondrocytes isolated from rabbit articular cartilage were cultured and verified by immunocytochemical staining of type II collagen. Chondrocyte viability was assessed after being treated with HBP-A in different concentrations. Morphological status of chondrocytes-alginate hydrogel constructs in vitro was observed by scanning electron microscope (SEM). The constructs were treated with HBP-A and then injected to nude mice subcutaneously. Six weeks after transplantation, the specimens were observed through transmission electron microscopy (TEM). The mRNA expressions of disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTs-5), aggrecan and type II collagen in both monolayer culture and constructs were determined by real time polymerase chain reaction (PCR). The expression of type II collagen and matrix metalloproteinases-3 (MMP-3) in chondrocyte monolayer culture was also tested through Western blot and enzyme linked immunosorbent assay (ELISA), respectively. RESULTS: MMP-3 secretion and ADAMTs-5 mRNA expression in vitro were inhibited by HBP-A at 0.3 mg/mL concentration. In morphological study, there were significant appearance of collagen in those constructs treated by HBP-A. Accordingly, in both chondrocyte monolayer culture and chondrocytes-alginate hydrogel constructs, the expression of type II collagen was increased significantly in HBP-A group when compared with control group (P<0.001). CONCLUSIONS: The study documented that the potential pharmacological target of glucan HBP-A in chondrocytes monolayer culture and tissue engineered cartilage in vivo may be concerned with the inhibition of catabolic enzymes MMP-3, ADAMTs-5, and increasing of type II collagen expression.

Adverse events of massage therapy in pain-related conditions: a systematic review.

Pain-related massage, important in traditional Eastern medicine, is increasingly used in the Western world. So the widening acceptance demands continual safety assessment. This review is an evaluation of the frequency and severity of adverse events (AEs) reported mainly for pain-related massage between 2003 and 2013. Relevant all-languages reports in 6 databases were identified and assessed by two coauthors. During the 11-year period, 40 reports of 138 AEs were associated with massage. Author, year of publication, country of occurrence, participant related (age, sex) or number of patients affected, the details of manual therapy, and clinician type were extracted. Disc herniation, soft tissue trauma, neurologic compromise, spinal cord injury, dissection of the vertebral arteries, and others were the main complications of massage. Spinal manipulation in massage has repeatedly been associated with serious AEs especially. Clearly, massage therapies are not totally devoid of risks. But the incidence of such events is low.

[Case-control study on close manipulative reduction combined with minimally invasive percutaneous plate fixation for the treatment of proximal humeral fractures].

OBJECTIVE: To compare the clinical effects of close manipulative reduction combined with minimally invasive percutaneous plate fixation(MIPPO) and conventional open reduction and internal fixation (ORIF) for the treatment of proximal humerus fractures. METHODS: From April 2008 to March 2013, among the 75 patients with fractures of proximal humerus, 26 patients were male and 49 patients were female, ranging in age from 22 to 80 years; 18 patients had injuries caused by traffic accident and 57 patients had injuries caused by falling down. According to Neer classification, there were 49 cases of two-part fractures and 26 cases of three-part fractures. All the patients were divided into two groups: MIPPO group and ORIF group. There were 12 males and 21 females in the MIPPO group,including 22 cases of Neer two parts and 11 cases of Neer three parts, who were treated with close manipulative reduction combined with MIPPO. While the other 42 patients were in the ORIF group,including 16 males and 26 females. Among those patients,27 cases belonged to Neer two parts and 15 cases of Neer three parts, who were treated with ORIF. Length of the incision, blood loss, operating time, early postoperative pain(recorded by VAS), neck-shaft angle of proximal humerus and postoperative function of shoulder(recorded by Constant-Murley score, including pain, function, ROM and muscle length) were compared. RESULTS: The mean lengths of incision were (6.74 +/- 0.38) cm in MIPPO group and (16.82 +/- 1.74) cm in ORIF group;blood losses were (110.15 +/- 29.49) ml in MIPPO group and (326.19 +/- 59.71) ml in ORIF group; operation times were (48.60 +/- 10.18) min in MIPPO group and (68.84-16.22) min in ORIF group. VAS of patients in MIPPO group on the 1st and 3rd days postoperatively were lower than those of patients in the ORIF group. The postoperative radiographs verified good position of all screws and satisfactory reduction of bone fracture reduction in both groups. All the patients were followed up,and the durig ranged from 8 to 24 months (mean 14.2 months). In the MIPPO group, there was no humeral head necrosis and all patients gained bone union; while in the ORIF group, 3 patients sustained nonunion and received reoperation for bone grafting, and 2 patients sustained humeral head necrosis. The mean Constant-Murley scores of shoulder were 88.94 +/- 2.57 in the MIPPO group and 86.00 +/- 3.36 in the ORIF group. CONCLUSION: The close manipulative reduction combined with MIPPO is a better choice for fixation of proximal humerus fractures, compared with conventional plate. This method possesses such advantages as a shorter incision, less disturbance of the blood supply and stable fixation of the fracture, allowing early exercise so that the function of shoulder recovers rapidly.

Effectiveness, medication patterns, and adverse events of traditional chinese herbal patches for osteoarthritis: a systematic review.

Objective. The aim of this study is to systematically evaluate the evidence whether traditional Chinese herbal patches (TCHPs) for osteoarthritis (OA) are effective and safe and analyze their medication patterns. Methods. A systematic literature search was performed using all the possible Medical Subject Headings (MeSH) and keywords from January 1979 to July 2013. Both randomized controlled trials (RCTs) and observational studies were included. Estimated effects were analyzed using mean difference (MD) or relative risk (RR) with 95% confidence intervals (CI) and meta-analysis. Results. 86 kinds of TCHPs were identified. RCTs and controlled clinical trials (CCTs) which were mostly of low quality favored TCHPs for local pain and dysfunction relief. TCHPs, compared with diclofenac ointment, had significant effects on global effectiveness rate (RR = 0.50; 95% CI (0.29, 0.87)). Components of formulae were mainly based on the compounds "Xiao Huo Luo Dan" (Minor collateral-freeing pill) and "Du Huo Ji Sheng Tang" (Angelicae Pubescentis and Loranthi decoction). Ten kinds of adverse events (AEs), mainly consisting of itching and/or local skin rashes, were identified after 3-4 weeks of follow-up. Conclusions. TCHPs have certain evidence in improving global effectiveness rate for OA; however, more rigorous studies are warranted to support their use.

[Application of biomarker CTX- II in osteoarthritis].

Effective biomarkers for clinical usage of osteoarthritis are still limited. It was confirmed that C-terminal crosslinking telopeptide of type I collagen (CTX- II) was a specific marker reflecting degradation of articular cartilage. Detection of CTX- II could promptly reflect level of cartilage injury and degradation ,diagnose OA,predict its progress,monitor effects of drug treatment, thus, reflect the condition of osteoarthritis patient indirectly. Application of CTX- II focused mainly on in the early stage of OA and need together to detect with other biomarkers,in order to more accurately reflection of the pathological changes of OA,but the specific clinical significance of CTX- II results still need to improve further.

[Study on the diagnostic value of whole-organ magnetic resonance imaging score (WORMS) in knee osteoarthritis].

OBJECTIVE: To explore the diagnostic value of whole-organ magnetic resonance imaging score (WORMS) in knee osteoarthritis (KOA). METHODS: From November 2009 to January 2011,70 patients with KOA combined with knee effusion among outpatient and inpatient were analyzed retrospectively. Among the patients, 12 patients were male, 58 patients were female,ranging in age from 46 to 75 years,with a mean age of (59.66 +/- 9.93) years. The clinical symptoms were evaluated by WOMAC, the imaging of KOA was assessed by K-L score and WORMS, and COMP and CTX- II were measured respectively by ELISA. The correlation analyses and multiple linear regression analysis were studied to determine associations among biomarkers, clinical variables and radiographic findings of knee joints. RESULTS: The average scores of WOMAC and WORMS were (57.50 +/- 8.20) and (64.54 +/- 16.45) respectively. The median of CTX- II nd COMP were 2.42 ng/ml and 4.56 ng/ml respectively. Grouped by less than the lowest quartile and more than the highest quartile of WORMS, COMP was significantly different (Z=2.04, P=0.039), but there was no significant difference in CTX-II (Z=0.79, P=0.427). WORMS were positively correlated with WOMAC and K-L score (r=0.777, P<0.01; r=0.716, P<0.01; respectively); WOMAC was also positively correlated with K-L score (r=0.692, P<0.01). WORMS's cartilage, osteophytes and synovitis were positively correlated with WOMAC, K-L score and COMP respectively (r=0.771, P<0.01; r=0.509, P<0.01; r=0.917, P<0.01). It was determined by stepwise regression that the KOA was mainly affected by WORMS, K-L score (P=0.015, P=0.025 respectively) when WOMAC as a dependent variable, age, gender, K-L score, WORMS, COMP and CTX- II as independent variables (F=20.327, P<0.01). CONCLUSION: WORMS has a better reference value for diagnosis of KOA. The expression of COMP is high in the synovial fluid when WORMS at the high point. The clinical symptoms of knee osteoarthritis are mainly affected by WORMS and K-L score.

[Wnt signaling pathways and osteoarthritis].

The Wnt signaling exists in every kinds of species and regulates a variety of biological processes including cell fate, proliferation and function, immunity, stress, apoptosis and so on. During the researching, Wnt signaling also plays an important role in chondrocyte differentiation and maturation. So it has been the new spot in pathogenesis of osteoarthritis study.