Association between rheumatoid arthritis and chronic respiratory diseases in a Japanese population: A Mendelian randomization study.

Past observational studies have documented an association between rheumatoid arthritis (RA) and chronic respiratory diseases. Undertaking the approach of Mendelian randomization (MR) analysis, this research aims to delve deeper into the probability of a causal connection between RA and chronic respiratory diseases. Collated genome-wide association study data covering RA with 4199 cases against 208,254 controls, asthma comprising 8216 cases versus 201,592 controls, and chronic obstructive pulmonary disease (COPD) detailing 3315 cases in contrast to 201,592 controls were derived from the repository of the Japanese Biobank. A selection of 10 RA-related, 8 asthma-related, and 4 COPD-related single nucleotide polymorphisms notable for their statistical significance (P < 5 × 10-8) were identified as instrumental variables. The primary analytical technique was the inverse variance-weighted (IVW) method, alongside the MR-Egger protocol, weighted median, and weighted mode to reinforce the validity and solidity of the principal results. For scrutinizing possible implications of horizontal pleiotropy, we harnessed the MR-Egger intercept examination and the Mendelian Randomization Pleiotropy REsidual Sum and Outlier test. Employing the inverse variance-weighted technique, we established a positive correlation between genetic predispositions for RA and actual occurrences of asthma (odds ratios [OR] = 1.14; 95% confidence intervals [CI]: 1.04-1.24; P = .003). This correlation remained strong when testing the results utilizing various methods, including the MR-Egger method (OR = 1.32; 95% CI: 1.09-1.60; P = .023), the weighted median (OR = 1.16; 95% CI: 1.06-1.26; P < .001), and the weighted mode (OR = 1.21; 95% CI: 1.11-1.32; P = .002). Furthermore, our findings from the inverse variance-weighted method also demonstrated a positive association between genetically predicted RA and COPD (OR = 1.12; 95% CI: 1.02-1.29; P = .021). However, no such link was discerned in supplementary analyses. In a shifted perspective-the reverse MR analysis-no correlation was identified between genetically predicted instances of asthma (IVW, P = .717) or COPD (IVW, P = .177) and RA. The findings confirm a causal correlation between genetically predicted RA and an elevated risk of either asthma or COPD. In contrast, our results offer no support to the presumed causal relationship between genetic susceptibility to either asthma or COPD and the subsequent development of RA.

Intra-articular injection of tranexamic acid in patients with haemophilia arthritis: retrospective controlled study in total knee arthroplasty.

PURPOSE: Total knee arthroplasty is the main method for the treatment of advanced haemophilic knee arthritis. Due to the particularity of hemophilia, the blood management plan is the focus of the perioperative period for haemophilia patients. This study aimed to investigate the clinical effect and safety of intra-articular injection of tranexamic acid in patients with haemophilia. METHODS: This is a retrospective study. According to whether tranexamic acid is used or not, patients are divided into tranexamic acid group (n=30) and non-tranexamic acid group (n=29). Total blood loss, intraoperative blood loss, complete blood count, total amount of coagulation factor VIII (FVIII) usage, coagulation biomarkers, inflammatory biomarkers, knee range of motion, knee joint function, pain status, complication rate, and patient satisfaction were assessed and compared at a mean follow-up of 16 months. RESULTS: Injecting tranexamic acid into the knee joint cavity can effectively reduce the hidden blood loss and total blood loss (P<0.001), and reduce the patient's early postoperative inflammation biomarkers, pain status, and limb swelling. Therefore, the patient can obtain a better range of motion following total knee arthroplasty. In the long run, in terms of joint function and surgical satisfaction, there are no statistically significant differences. In addition, there are no statistically significant differences between the two groups of patients in terms of the total amount of FVIII usage, length of stay, and hospitalization expenses. CONCLUSION: In patients with haemophilia, intra-articular injection of tranexamic acid during total knee arthroplasty can effectively reduce postoperative blood loss, early postoperative inflammation levels, pain and limb swelling, and enable patients to receive higher-quality rehabilitation exercises to get better joint function. Previous studies on TKA in haemophilic patients have already demonstrated the efficacy of intra-articular injections of TXA in reducing postoperative blood loss. Our study confirms this efficacy.

Osteoporosis and associated risk factors in patients with severe hemophilia A: a case-control study from China.

INTRODUCTION: People with hemophilia risk osteoporosis more than healthy people, which may be related to specific factors. METHODS: This case-control study included 53 patients with severe hemophilia type A and 49 healthy participants. Dual-energy X-ray absorptiometry (DXA) was used to determine bone mineral density (BMD). Collected information on age, body mass index (BMI), number of joint arthropathies, functional independence score in hemophilia (FISH), bone turnover markers, antibodies, treatment modalities. Identified independent risk factors for osteoporosis. RESULTS: The BMD of the femoral neck (0.80 g/cm2vs.0.97 g/cm2), ward's triangle (0.62 g/cm2vs.0.83 g/cm2), tuberosity (0.63 g/cm2vs.0.80 g/cm2) and hip (0.80 g/cm2vs.0.98 g/ cm2) in the case group were significantly lower than those in the control group, all of which were P < 0.001. However, there was no significant difference in the overall BMD of lumbar spine(L1-L4) (1.07 g / cm2vs. 1.11 g / cm2). The frequency of osteoporosis in the case group was 41.51%. BMI and FISH score were considered as independent risk factors for BMD decrease. CONCLUSION: The BMD of patients with severe hemophilia A is much lower than that of healthy population, and this difference is mainly reflected in the hip. The clear influencing factors were low BMI and functional independence decrease. Osteoclast was active while osteoblast activity was not enhanced synchronously, which may be the pathological mechanism of BMD decrease.

Quercetin mediates TSC2-RHEB-mTOR pathway to regulate chondrocytes autophagy in knee osteoarthritis.

OBJECTIVE: This study aimed to explore the specific molecular mechanism of the therapeutic effect of quercetin in knee osteoarthritis (KOA). METHODS: The KOA rat model was constructed by excising the medial meniscus and transecting the anterior meniscus. Joint injuries in rats were determined by Hematoxylin-Eosin (H&E) and Safranin O staining. The severity of KOA was then assessed according to the Osteoarthritis Research Society International (OARSI). The expressions of TSC2 and LC2B in joint tissue were measured by immunohistochemistry. Besides, chondrocytes treated with 10 ng/ml IL-1ß were used to construct a chondrocyte arthritis model, while those treated with 4 or 8 µM quercetin were served as treatment groups. MTT, flow cytometry and toluidine blue staining were used to detect cell viability, apoptosis and mucopolysaccharide synthesis, respectively. qRT-PCR or Western blot was performed to determine the expressions of MMP-13, collagen II, Aggrecan, TSC2, RHEB, mTOR, p-mTOR, ULK1, p-ULK1, LC3B-I, LC3B-II and P62 in chondrocytes. RESULTS: Quercetin alleviated the joint injury and suppressed the increase in MMP-13 expression and the decreases in collagen II and Aggrecan expressions in KOA rats. In addition, quercetin suppressed RHEB, p-mTOR, p-ULK1 and P62 expressions but promoted TSC2 and LC3BII expressions in KOA rats. Furthermore, quercetin could relieve the decrease of cell viability and the increase of apoptosis that induced by IL-1ß, and promote the synthesis of IL-1ß-inhibited mucopolysaccharide in chondrocytes. Nevertheless, siTSC2 partially offset the therapeutic effects of quercetin in chondrocytes. CONCLUSION: Quercetin alleviated KOA by mediating the TSC2-RHBE-mTOR signaling pathway.

[Progress on surgical treatment for hemophiliac arthropathy].

Surgical treatment is the main treatment for hemophilia arthritis, including synoviectomy, joint replacement and joint fusion. Synoviectomy is suitable for early hemophilia synovitis, and is divided into radiation, chemical, arthroscopy, and open operation. Radionuclides were recommended as the first choice due to its positive efficacy and less side effects, but exsit some problems such as scarcity of nuclides. Chemical synoviectomy is cheap and easy to operate, which is suitable for developing countriesm, while mutiple doses and pain after injection are main fault. Synoviectomy under arthroscope has a significant effect on the advanced lesion, but has a higher surgical risk. Open surgery with severe trauma and postoperative joint stiffness, is rarely performed. Joint replacement could effectively improve range of motion in advanced patients and is suitable for joints with high range of motion. Arthrodesis are effective in improving symptoms but lead to loss of range of motion and are suitable for joints with low range of motion. Operation for hemophilia arthritis has some problems, such as single operation, untimely diagnosis and treatment in early stage, and unsatisfactory curative effect in late stage. In addition, the treatment of hemophilia arthritis should focus on the early treatment, the formation of the whole process, the system of individual treatment concept.