Objective Obesity is a risk factor for knee osteoarthritis (KOA) development and progression. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are indicated for type 2 diabetes mellitus (T2DM) and obesity. However, whether KOA patients can benefit from GLP-1RA therapies has not been sufficiently investigated, especially in the long term. Methods The Shanghai Osteoarthritis Cohort study is a prospective, observational, multicentre study of >40 000 adults with clinically diagnosed osteoarthritis aged >45 years in Shanghai. We identified all KOA participants with comorbid T2DM enrolled from 1 January 2011 to 1 January 2017. Primary outcome was incidence of knee surgery after enrolment. Secondary outcomes included pain-relieving medication use, number of intra-articular therapies, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and medial femorotibial joint cartilage thickness. To evaluate the effects of GLP-1RA, we performed before-and-after comparison and comparison with participants who had no GLP-1RA exposure. Results For an intergroup comparison (non-GLP-1RA vs GLP-1RA), more weight loss (adjusted mean difference in weight change from baseline −7.29 kg (95% CI −8.07 to −6.50 kg), p<0.001) and lower incidence of knee surgery (93/1574 (5.9%) vs 4/233 (1.7%), adjusted p=0.014) were observed in the GLP-1RA group. Statistically significant differences in mean change from baseline for the WOMAC total and pain subscale scores were observed (adjusted mean difference in WOMAC total score −1.46 (95% CI −2.84 to −0.08), p=0.038; adjusted mean difference in WOMAC pain subscore −3.37 (95% CI −5.79 to −0.94), p=0.007). Cartilage-loss velocity of the medial femorotibial joint was significantly lower in the GLP-1RA group postadjustment for baseline characteristics (adjusted mean difference −0.02 mm (95% CI −0.03 to −0.002 mm), p=0.004). For the before-and-after comparison within the GLP-1RA group, we observed a significant decrease of symptom-relieving medication consumption and cartilage loss velocity of medial femorotibial joint (after-treatment vs before-treatment: −0.03±0.05 vs −0.05±0.07 mm/year, p<0.001). The association between GLP-1RA exposure and decreased incidence of knee surgery was mediated by weight reduction (mediation proportion: 32.1%), instead of glycaemic control (too small to calculate). Conclusion With sufficient treatment duration, GLP-1RA therapies might be disease-modifying for KOA patients with comorbid T2DM, possibly mediated by weight loss. Further investigation is needed to elucidate effects of GLP-1RA on disease process, joint structure and patient-reported outcomes of osteoarthritis.

The pHs of extracellular fluids (ECFs) in normal tissues are commonly maintained at 7.35 to 7.45. The acidification of the ECF is one of the major characteristics of tumour microenvironment. In this study, we report that decreased extracellular pH promotes the transformation of mesenchymal stem cells (MSCs) into cancer-associated fibroblasts (CAFs), termed CAF activation. Furthermore, we demonstrate that GPR68, a proton-sensing G-protein-coupled receptor (GPCR), is required for the pH-dependent regulation of the differentiation of MSCs into CAFs. We then identify Yes-associated protein 1 (YAP) as a downstream effector of GPR68 for CAF activation. Finally, we show that knockdown of GPR68 in MSCs can prevent the CAF activation under cancer microenvironment. Systemic transplantation of GPR68-silenced MSCs suppresses in-situ tumour growth and prolong life span after cancer graft.

Chronic ankle instability (CAI) is a common sequela following an acute lateral ankle sprain (LAS). To treat an acute LAS more effectively and efficiently, it is important to identify patients at substantial risk for developing CAI. This study identifies magnetic resonance imaging (MRI) manifestations for predicting CAI development after a first episode of LAS and explores appropriate clinical indications for ordering MRI scans for these patients. All patients with a first-episode LAS who received plain radiograph and MRI scanning within the first 2 weeks after LAS from December 1, 2017 to December 1, 2019 were identified. Data were collected using the Cumberland Ankle Instability Tool at final follow-up. Demographic and other related clinical variables, including age, sex, body mass index, and treatment were also recorded. Univariable and multivariable analyses were performed successively to identify risk factors for CAI after first-episode LAS. A total 131 out of 362 patients with a mean follow-up of 3.0 ± 0.6 years (mean ± SD; 2.0-4.1 years) developed CAI after first-episode LAS. According to multivariable regression, development of CAI after first-episode LAS was associated with 5 prognostic factors: age (odds ratio (OR) = 0.96, 95% confidence interval (95%CI): 0.93-1.00, p = 0.032); body mass index (OR = 1.09, 95%CI: 1.02-1.17, p = 0.009); posterior talofibular ligament injury (OR = 2.17, 95%CI: 1.05-4.48, p = 0.035); large bone marrow lesion of the talus (OR = 2.69, 95%CI: 1.30-5.58, p = 0.008), and Grade 2 effusion of the tibiotalar joint (OR = 2.61, 95%CI: 1.39-4.89, p = 0.003). When patients had at least 1 positive clinical finding in the 10-m walk test, anterior drawer test, or inversion tilt test, they had a 90.2% sensitivity and 77.4% specificity in terms of detecting at least 1 prognostic factor by MRI. MRI scanning is valuable in predicting CAI after first-episode LAS for those patients with at least 1 positive clinical finding in the 10-m walk test, anterior drawer test, and inversion tilt test. Further prospective and large-scale studies are necessary for validation.

Background: The functional outcomes and therapeutic costs between digit replantation and revision amputation have remained controversial. Methods: A total of 1023 patients with single-digit traumatic amputation or devascularization who underwent successful digit replantation (failure excluded) or revision amputation from January 1, 2013, to January 1, 2016, were included in this study. All cases were subgrouped based on Tamai level of amputation and the injured digit. The clinical outcomes were assessed using the Michigan Hand Outcomes Questionnaire 1 year after the initial operation. The authors also compared the cost of treatment, the duration of hospitalization, and the duration of sick leave between the two treatments. Results: Replantation of small (level I to V), ring (level I to III), and long (level I) fingers showed no functional benefit compared with initial revision amputation. In contrast, replantation of thumb (level I to V), index (level I to V), long (level II to V), and ring (level IV to V) fingers had better outcomes. The cost of replantation was higher and the durations of hospitalization and sick leave of replantation were also longer compared with the revision amputation group. Conclusions: Single amputated injuries of small (level I to V), ring (level I to III), and long (level I) fingers are a relative contradiction for replantation. Replantation of thumb (level I to V), index (level I to V), long (level II to V), and ring (level IV to V) fingers showed extra benefit compared with revision amputation.