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.

Perioperative Blood Loss Can Be Reduced If Total Knee Arthroplasty Was Performed in the Si Hour-Period, Compared with the Wei Hour-Period: A Retrospective Cohort Study.

OBJECTIVE: To investigate the efficacy and safety of performing primary unilateral total knee arthroplasty (TKA) in the "Si hour-period" meaning 09:00 a.m. to 11:00 a.m. (one of the 12 two-hour periods into which the day was traditionally divided, each being given the name of one of the 12 earthly branches), compared with the "Wei hour-period" (13:00-15:00). METHODS: Patient documentations were studied for those who underwent a primary unilateral TKA performed by the same surgical team with a tourniquet between January 2018 and January 2021 at our medical center. Eighty-four patients were enrolled and assigned into group A (in Si hour-period) and group B (in Wei hour-period). The main outcomes were total blood cell loss (TBL), hidden blood loss (HBL), visible blood loss (VBL), maximum hemoglobin (Hb) drop, and transfusion rate. Secondary outcomes were length of hospital stay (LOS), postoperative femorotibial mechanical axis (FTMA), FTMA correction, platelet count, plasma D-dimer (D-D), prothrombin time (PT), international normalized ratio (INR), and the incidence of postoperative complications. RESULTS: Group A showed statistical significance lower at the mean TBL, the mean HBL, and the maximum Hb drop (95% CI: -352.8 to -46.1,P=0.011, 95% CI: -348.0 to -40.1,P=0.014, and 95% CI: -9.5 to -0.7,P=0.023, respectively) after TKA than group B. The postoperative platelet count of group A was more significant than that of group B (95% CI:3.1 to 52.9, P=0.028). The VBL, transfusion rate, the LOS, postoperative FTMA, FTMA correction, plasma D-D, PT, INR, and the incidence of postoperative complications (wound complications, calf muscular vein thrombosis, infection, pulmonary embolism, and deep vein thrombosis) were similar between the two groups (P > 0.05, respectively). CONCLUSION: Our study shows that blood loss can be reduced when TKA is performed in the "Si hour-period," which may be due to increasing platelet count, and postoperative complications did not increase, compared with the Wei hour-period. We recommend that the selective operation, such as TKA, should be performed in the "Si hour-period" in clinical practice between the two hour-period.