BACKGROUND:The content of serum thrombin in patients with osteoarthritis is significantly higher than that in normal individuals,and thrombin can induce inflammatory degeneration of rat chondrocytes,suggesting that inhibiting the function of thrombin may become a method for treating osteoarthritis.Celecoxib is a common therapeutic drug for the clinical treatment of osteoarthritis.It is not yet known whether it improves chondrocyte degeneration by inhibiting the activity of thrombin. OBJECTIVE:To investigate the effect of celecoxib on thrombin-induced degeneration of rat chondrocytes. METHODS:Thrombin levels in the serum of osteoarthritis patients and normal individuals were detected by an ELISA kit.Primary chondrocytes of neonatal Sprague-Dawley rats were isolated,and all experiments were performed with cells from passage one.Chondrocytes were randomly divided into three groups:control group,thrombin group,and celecoxib group.The cell morphology of the three groups was observed under an inverted microscope,and an Edu kit was used to detect the cell proliferation.qRT-PCR was used to detect the expression of extracellular matrix components(aggrecan,elastin,cartilage oligomeric matrix proteins),inflammatory factors(interleukin-1,interleukin-6,and tumor necrosis factor-α),and chemokines(monocyte chemotactic protein 2,monocyte chemotactic protein 7,granulocyte chemotactic protein 6).The expression of type 2 collagen α1 was detected by immunofluorescence.Western blot method was used to detect the expression of catabolic metabolism genes,such as matrix metalloproteinase 9,matrix metalloproteinase 13,and cyclooxygenase 2. RESULTS AND CONCLUSION:Patients with osteoarthritis had higher levels of thrombin in the serum compared with normal individuals.Under the microscope,celecoxib was found to significantly inhibit fibroid changes in chondrocytes.Compared with the thrombin group,celecoxib inhibited the proliferation of chondrocytes.The downregulation of extracellular matrix gene expression,such as type II collagen α1,in the thrombin group was inhibited by celecoxib(P<0.05).Thrombin promoted the expression of inflammatory factors(interleukin-1,interleukin-6,and tumor necrosis factor-α),chemokines(monocyte chemotactic protein 2,monocyte chemotactic protein 7,granulocyte chemotactic protein 6),as well as catabolic genes(matrix metalloproteinase 9,matrix metalloproteinase 13,and cyclooxygenase 2),and under the intervention of celecoxib,the expression of these genes could be downregulated(P<0.05).Overall,these findings indicate that celecoxib inhibits the pro-inflammatory effects of thrombin and thereby ameliorates chondrocyte degeneration in rats.

Objective To investigate the incidence and influencing factors of right-to-left shunt(RLS)in patients with iatrogenic atrial septal defect(iASD)after atrial septal puncture during in-terventional therapy for atrial fibrillation and analyze the correlation with new onset migraine in order to provide a basis for the prevention and treatment of related clinical events.Methods A to-tal of 54 patients with atrial fibrillation who underwent interventional surgery[including radio-frequency catheter ablation(RFCA),left atrial appendage closure(LAAC),and'one-stop'sur-gery]in cardiologic department of our hospital from November 2022 to March 2023 were enrolled in this study.According to existence of RLS in iASD within 48 h after surgery,they were divided into RLS group(24 patients)and non-RLS group(30 patients).The general information and tran-sthoracic echocardiographic data were collected and analyzed for the occurrence and influencing factors of RLS.The incidence of new onset migraine within 3 months after operation was recorded in both groups.Results All these patients had left-to-right shunt of iASD,24 patients had RLS(44.44％),and the defect size was 5.12±0.80 mm.During the 3 months'follow-up period,there was no significant difference in the incidence of new onset migraine between the two groups(P＞0.05).Older age,increased proportion of persistent atrial fibrillation,and larger iASD size was seen in the RLS group than the non-RLS group(P＜0.05,P＜0.01).Multivariate logistic regres-sion analysis showed that iASD size was a risk factor for RLS(OR=2.245,95％CI:1.040-4.846,P=0.040).Conclusion RLS is common in iASD after interventional treatment of atrial fibrillation,which is not related to the early occurrence of new onset migraine in these patients.The size of iASD is a risk factor for RLS.At the same time,more attention should be paid to the influence of iASD on hemodynamics and clinical events.