Circular RNA CREBBP modulates cartilage degradation by activating the Smad1/5 pathway through the TGFß2/ALK1 axis.

Osteoarthritis, characterized by articular cartilage degradation, is the leading cause of chronic disability in older adults. Studies have indicated that circular RNAs are crucial regulators of chondrocyte development and are involved in the progression of osteoarthritis. In this study, we investigated the function and mechanism of a circular RNA and its potential for osteoarthritis therapy. The expression levels of circCREBBP, screened by circular RNA sequencing during chondrogenic differentiation in adipose tissue-derived stem cells, and TGFß2 were significantly increased in the cartilage of patients with osteoarthritis and IL-1ß-induced chondrocytes. circCREBBP knockdown increased anabolism in the extracellular matrix and inhibited chondrocyte degeneration, whereas circCREBBP overexpression led to the opposite effects. Luciferase reporter assays, rescue experiments, RNA immunoprecipitation, and RNA pulldown assays confirmed that circCREBBP upregulated TGFß2 expression by sponging miR-1208, resulting in significantly enhanced phosphorylation of Smad1/5 in chondrocytes. Moreover, intra-articular injection of adeno-associated virus-sh-circCrebbp alleviated osteoarthritis in a mouse model of destabilization of the medial meniscus. Our findings reveal a critical role for circCREBBP in the progression of osteoarthritis and provide a potential target for osteoarthritis therapy.

[Comparison of hemostatic effect and safety in primary unilateral total hip arthroplasty receiving different anticoagulants after anti-fibrinolysis with tranexamic acid].

OBJECTIVE: To compare the hemostatic effect and safety in primary unilateral total hip arthroplasty (THA) receiving nadroparin calcium, enoxaparin sodium, rivaroxaban, or apixaban after anti-fibrinolysis with tranexamic acid (TXA) and explore the best anticoagulant. METHODS: A retrospective analysis was conducted on 184 patients who underwent the primary unilateral THA between January 2014 and December 2018, administrated 15 mg/kg TXA before surgery and received nadroparin calcium, enoxaparin sodium, rivaroxaban, or apixaban. The patients were divided into four groups based on the different anticoagulants: 46 patients received nadroparin calcium; 45 patients received enoxaparin sodium; 47 patients received rivaroxaban; the other 46 patients received apixaban. There was no significant difference in age, gender, body mass, body mass index, the types of hip joint diseases, complications, anesthesia mode, operation time, and preoperative laboratory indexes (hemoglobin, hematocrit, platelet, prothrombin time, activated partial prothrombin time, blood volume) ( P>0.05). Perioperative blood data (total blood loss, hidden blood loss, dominant blood loss, postoperative drainage volume, maximum loss of hemoglobin, and blood transfusion rate) and complications (incision, bleeding, and thrombosis) were recorded and compared between groups. RESULTS: There was no significant difference in total blood loss, hidden blood loss, dominant blood loss, postoperative drainage volume, maximum loss of hemoglobin, and blood transfusion rate between groups ( P>0.05). The comparison of postoperative complications showed that 1 case (2.1%) of redness and swelling of incision occurred in the rivaroxaban group, and 1 case (2.2%) of the other 3 groups each had poor incision healing. No incision infection, fat liquefaction, or other incision complications occurred in the 4 groups. There was no significant difference in incision complication between groups ( P>0.05). There were 2 cases (4.3%) bleeding events (1 case of right inguinal hematoma and 1 case of subcutaneous ecchymosis in front of left leg) in the nadroparin calcium group, while no bleeding event occurred in the other 3 groups, which had no significant difference in bleeding complication between groups ( χ 2=5.612, P=0.132). There was 1 case (2.2%) of intermuscular vein thrombosis of the lower extremity in the nadroparin calcium group and no case in the other 3 groups, which had no significant difference between groups ( χ 2=2.789, P=0.425). Neither deep venous thrombosis nor pulmonary embolism occurred in any group. CONCLUSION: No significant difference in the hemostatic effect and incidences of complications for patients underwent primary unilateral THA receiving nadroparin calcium, enoxaparin sodium, rivaroxaban, or apixaban after anti-fibrinolysis with TXA. One of the four anticoagulants can be selected to prevent thrombosis after anti-fibrinolysis with TXA, which has certain safety.

[Analysis of hemostatic effect and safety of tranexamic acid in primary simultaneous bilateral total hip arthroplasty].

OBJECTIVE: To explore the effect of tranexamic acid (TXA) on the transfusion rate, dominant blood loss, and postoperative complications in simultaneous bilateral total hip arthroplasty (SBTHA). METHODS: A clinical data of 72 patients who underwent the primary SBTHA between January 2010 and December 2018 was retrospectively analyzed. A single dose of 15 mg/kg TXA was administered intravenously before 5-10 minutes of operation in 48 patients of trial group and 24 patients were not treated with TXA in the control group. There was no significant difference between the two groups ( P>0.05) in the gender, age, body mass index, the type of disease, American Society of Anesthesiologists (ASA) grading, comorbidity, and preoperative hospital stay, hemoglobin, hematocrit, platelet count, coagulation function tests. The operation time, intraoperative blood loss, and postoperative transfusion rate, dominant blood loss, complication, and hospital stay were recorded and compared between the two groups. RESULTS: The median operation time of the trial group was 208.0 minutes, and that of the control group was 202.5 minutes, with no significant difference ( Z=-1.046, P=0.295). Postoperative transfusion was performed in 26 patients (54.2%) in the trial group and 21 patients (87.5%) in the control group, and the difference of transfusion rate between the two groups was significant ( χ 2 =7.843, P=0.005). However, there was no significant difference in the amount of transfused suspended red blood cells and plasma between the two groups ( P>0.05). The median intraoperative blood loss was 550 mL in the trial group and 600 mL in the control group, with no significant difference ( Z=-1.378, P=0.168). The postoperative drainage volume and median dominant blood loss in the trial group were (542±269) and 1 050 mL, respectively, which were significantly lower than those in the control group [(710±316) and 1 270 mL] ( P<0.05). There was 1 case of skin tension blisters around the incision, 1 case of lower limb numbness and muscle strength loss, and 1 case of lacunar cerebral infarction in the trial group, while in the control group, there was 1 case of skin ecchymosis around the incision and 1 case of bilateral lower limb numbness and muscle strength loss, which showed no significant difference in the incidences of complications ( P>0.05). No pulmonary embolism or deep venous thrombosis was found in the two groups. The median postoperative hospital stay and median total hospital stay were 9.0 and 13.0 days in the trial group, while 9.0 and 13.0 days in the control group, respectively, with no significant difference ( P>0.05). CONCLUSION: For patients who are treated with the primary SBTHA, TXA can reduce transfusion rate and perioperative dominant blood loss, and has a good hemostatic effect without increasing complications of incision, pulmonary embolism, deep venous thrombosis, and hospital stay. Therefore, TXA is relative safe.