Malvidin attenuates trauma-induced heterotopic ossification of tendon in rats by targeting Rheb for degradation via the ubiquitin-proteasome pathway.

The pathogenesis of trauma-induced heterotopic ossification (HO) in the tendon remains unclear, posing a challenging hurdle in treatment. Recognizing inflammation as the root cause of HO, anti-inflammatory agents hold promise for its management. Malvidin (MA), possessing anti-inflammatory properties, emerges as a potential agent to impede HO progression. This study aimed to investigate the effect of MA in treating trauma-induced HO and unravel its underlying mechanisms. Herein, the effectiveness of MA in preventing HO formation was assessed through local injection in a rat model. The potential mechanism underlying MA's treatment was investigated in the tendon-resident progenitor cells of tendon-derived stem cells (TDSCs), exploring its pathway in HO formation. The findings demonstrated that MA effectively hindered the osteogenic differentiation of TDSCs by inhibiting the mTORC1 signalling pathway, consequently impeding the progression of trauma-induced HO of Achilles tendon in rats. Specifically, MA facilitated the degradation of Rheb through the K48-linked ubiquitination-proteasome pathway by modulating USP4 and intercepted the interaction between Rheb and the mTORC1 complex, thus inhibiting the mTORC1 signalling pathway. Hence, MA presents itself as a promising candidate for treating trauma-induced HO in the Achilles tendon, acting by targeting Rheb for degradation through the ubiquitin-proteasome pathway.

Efficacy of reinforcing sutures for prevention of anastomotic leakage after low anterior resection for rectal cancer: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Anastomotic leakage is a serious complication following surgery for cancer of the rectum. It is not clear whether reinforcing sutures could prevent anastomotic leakage. Therefore, this study aims at evaluating the efficacy of reinforcing sutures on anastomotic leakage. METHODS: We searched PubMed, Embase, and the Cochrane Library databases from inception to January 31, 2023. We included studies comparing anastomosis with reinforcing sutures to anastomosis without reinforcing sutures after low anterior resection. Risk of bias was assessed by the Cochrane tool for RCTs and the Risk of Bias in Non-Randomized Studies (ROBINS)-I tool for observational studies. The overall quality of evidence for primary outcome was assessed using Grading of Recommendations Assessment, Development, and Evaluations methodology. RESULTS: Two RCTs (345 patients) and four observational studies (783 patients) were included. Anastomotic leakage occurred in 4.4% (24 of 548) of patients with reinforcing sutures and 11.9% (69 of 580) of patients without reinforcing sutures. Meta-analysis showed a lower incidence of anastomotic leakage (RR, 0.41; 95% CI 0.25 to 0.66, low certainty) in patients with reinforcing sutures. Operative time (WMD, -3.66; 95% CI -18.58 to 11.25) and reoperation for anastomotic leakage (RR, 0.69; 95% CI 0.23 to 2.08) were similar between patients with reinforcing sutures and those without reinforcing sutures. CONCLUSIONS: While observational data suggest that, there is a clear benefit in terms of reducing the risk of anastomotic leakage with the use of reinforcing sutures, RCT data are less clear. Further large, prospective studies are warranted to determine whether a true clinically important benefit exists with this technique.