Objective:To explore the relevant risk factors for deep venous thrombosis (DVT) of lower limb occurring 3 months after joint replacement surgery.Methods:A retrospective analysis was conducted on the clinical data of 1,782 patients who underwent joint replacement surgery at Drum Tower Hospital, School of Medicine of Nanjing University, from February 2015 to December 2018. Of these, 1,298 were male and 484 were female, with an average age of 65.4±12.3 years (range, 18-95 years). Fourteen factors associated with DVT occurrence at 3 months were investigated, including age, gender, body mass index (BMI), season of surgery, preoperative coagulation function, type of surgery, selection of minimally invasive approach, occurrence of lower limb venous thrombosis 1 day after surgery, history of previous thrombotic diseases, smoking, tumors, diabetes, hypertension, and heart disease. Independent sample t-tests and chi-square tests were used to analyze the risk factors for DVT occurrence. Indicators with statistically significant differences were included in a binary logistic regression analysis to determine the risk factors for DVT 3 months after surgery. The risk prediction model was established according to the results of logistic regression analysis, and the receiver operating characteristic curve was drawn. The area under the curve of the prediction model was calculated. Results:A total of 1,782 patients were included. The overall incidence of DVT occurring 3 months after joint replacement surgery was 10.5% (187/1,782). The thrombosis group included 5 symptomatic cases and 182 asymptomatic cases, with 13 proximal and 174 distal cases. DVT was found in the iliac vein (1 case), femoral vein (10 cases), popliteal vein (8 cases), peroneal vein (14 cases), and intramuscular vein (168 cases). Single-factor analysis showed that female gender, increasing age, previous thrombotic disease, hypertension, surgery in autumn, and the occurrence of DVT on the first day after surgery were correlated with DVT occurring 3 months after joint replacement surgery ( P<0.05). After excluding the missing data, a total of 1,744 patients were included in the final analysis. DVT occurrence on the first day after surgery [ OR=7.498, 95% CI (5.312, 10.584), P<0.001], surgery in autumn [ OR=1.834, 95% CI (1.215, 2.769), P=0.004], age [ OR=1.024, 95% CI (1.007, 1.042), P=0.009], female gender [ OR=1.863, 95% CI(1.184, 2.931), P=0.007], and history of previous thrombotic diseases [ OR=0.012, 95% CI (1.136, 2.830), P=0.012] were found to be associated with DVT occurrence at 3 months after surgery. The area under the curve (AUC) for predicting DVT three months after hip or knee arthroplasty was 0.803 [95% CI (0.761, 0.844)]. Conclusion:Advanced age, female gender, history of previous thrombotic diseases, occurrence of DVT on the first day after surgery, and surgery in autumn are risk factors for DVT occurring 3 months after joint replacement surgery.

Background: and Purpose Non-high-density lipoprotein cholesterol (non-HDL-C), which represents the total cholesterol content of all pro-atherogenic lipoproteins, has recently been included as a new target for lipid-lowering therapy in high-risk atherosclerotic patients in multiple guidelines. Herein, we aimed to explore the relationship between non-HDL-C level and the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in preventing stroke recurrence. Methods: This study comprised a post hoc analysis of the CHANCE-2 (Ticagrelor or Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II) trial, from which 5,901 patients with complete data on non-HDL-C were included and categorized by median non-HDL-C levels, using a cutoff of 3.5 mmol/L. The primary efficacy and safety outcomes were recurrent stroke and severe or moderate bleeding within 90 days. Results: Ticagrelor-aspirin significantly reduced the risk of recurrent stroke in patients with low non-HDL-C (71 [4.8%] vs. 119 [7.7%]; adjusted hazard ratio [HR] 0.54; 95% confidence interval [CI], 0.40–0.74), but not in those with high non-HDL-C (107 [7.3%] vs. 108 [7.6%]; adjusted HR, 0.88; 95% CI, 0.67–1.16), compared with clopidogrel-aspirin (P for interaction=0.010). When analyzed as a continuous variable, the benefit of ticagrelor-aspirin for recurrent stroke decreased as non-HDL-C levels increased. No significant differences in the treatment assignments across the non-HDL-C groups were observed in terms of the rate of severe or moderate bleeding (5 [0.3%] vs. 8 [0.5%] in the low non-HDL-C group; 4 [0.3%] vs. 2 [0.1%] in the high non-HDL-C group; P for interaction=0.425). Conclusion CHANCE-2 participants with low non-HDL-C levels received more clinical benefit from ticagrelor-aspirin versus clopidogrel-aspirin compared to those with high non-HDL-C, following minor ischemic stroke or transient ischemic attack.

Objective To investigate the impact of overweight on the prognosis of patients with acute mild ischemic stroke or moderate-high risk transient ischemic attack (TIA). Methods A total of 366 patients with acute mild ischemic stroke or moderate-high risk TIA who carried CYP2C19 loss-of-function alleles were included in the study. Baseline data were collected at admission, and clinical outcomes were collected within 3 months post-onset (primary outcomes: stroke recurrences within 3 months post-onset; secondary outcomes: composite outcome of stroke recurrence or death within 3 months post-onset, vascular events, and quality of life within 3 months). Kaplan-Meier method was used to plot the cumulative incidence curve of outcomes. Multivariate Cox proportional hazards model and multivariate Logistic regression model were used to evaluate the relationship between overweight and clinical outcomes within 3 months post-onset in patientswith ischemic stroke or TIA. The integrated discrimination improvement index (IDI) and net reclassification improvement index (NRI) were calculated to assess the predictive value of adding body mass index (BMI, whether overweight or not) based on traditional models for predicting the prognosis of acute ischemic stroke or TIA. Results After 3 months of follow-up, 28 patients had stroke recurrence, 1 patient died, and 31 patients had vascular events. The Kaplan-Meier cumulative incidence curve showed that the cumulative incidences of stroke recurrence, stroke recurrence or death, and vascular events after 3 months of onset were lower in overweight patients compared with non-overweight patients (Log-rank P < 0.05). Multivariate analysis showed that compared with non-overweight patients, overweight patients had significantly reduced risks of stroke recurrence within 3 months (HR=0.24; 95%CI, 0.08 to 0.71), composite outcome of stroke recurrence or death (HR=0.24; 95%CI, 0.08 to 0.69), and vascular events (HR=0.22; 95%CI, 0.07 to 0.63), and significantly improved quality of life within 3 months (OR=0.39; 95%CI, 0.20 to 0.76). The IDI and NRI calculations showed that compared with traditional models, the new model adding BMI (whether overweight) had significantly improved predictive ability for the prognosis of acute ischemic stroke or TIA. Conclusion Overweight may be a protective factor for the prognosis of TIA patients with acute mild ischemic stroke or moderate-high risk who carry CYP2C19 loss-of-function alleles. Compared with non-overweight patients, overweight patients have reduced risks of stroke recurrence, composite outcome of stroke recurrence or death, and vascular events within 3 months post-onset, and improved quality of life within 3 months post-onset.

Objective:To explore the relevant risk factors for deep venous thrombosis (DVT) of lower limb occurring 3 months after joint replacement surgery.Methods:A retrospective analysis was conducted on the clinical data of 1,782 patients who underwent joint replacement surgery at Drum Tower Hospital, School of Medicine of Nanjing University, from February 2015 to December 2018. Of these, 1,298 were male and 484 were female, with an average age of 65.4±12.3 years (range, 18-95 years). Fourteen factors associated with DVT occurrence at 3 months were investigated, including age, gender, body mass index (BMI), season of surgery, preoperative coagulation function, type of surgery, selection of minimally invasive approach, occurrence of lower limb venous thrombosis 1 day after surgery, history of previous thrombotic diseases, smoking, tumors, diabetes, hypertension, and heart disease. Independent sample t-tests and chi-square tests were used to analyze the risk factors for DVT occurrence. Indicators with statistically significant differences were included in a binary logistic regression analysis to determine the risk factors for DVT 3 months after surgery. The risk prediction model was established according to the results of logistic regression analysis, and the receiver operating characteristic curve was drawn. The area under the curve of the prediction model was calculated. Results:A total of 1,782 patients were included. The overall incidence of DVT occurring 3 months after joint replacement surgery was 10.5% (187/1,782). The thrombosis group included 5 symptomatic cases and 182 asymptomatic cases, with 13 proximal and 174 distal cases. DVT was found in the iliac vein (1 case), femoral vein (10 cases), popliteal vein (8 cases), peroneal vein (14 cases), and intramuscular vein (168 cases). Single-factor analysis showed that female gender, increasing age, previous thrombotic disease, hypertension, surgery in autumn, and the occurrence of DVT on the first day after surgery were correlated with DVT occurring 3 months after joint replacement surgery ( P<0.05). After excluding the missing data, a total of 1,744 patients were included in the final analysis. DVT occurrence on the first day after surgery [ OR=7.498, 95% CI (5.312, 10.584), P<0.001], surgery in autumn [ OR=1.834, 95% CI (1.215, 2.769), P=0.004], age [ OR=1.024, 95% CI (1.007, 1.042), P=0.009], female gender [ OR=1.863, 95% CI(1.184, 2.931), P=0.007], and history of previous thrombotic diseases [ OR=0.012, 95% CI (1.136, 2.830), P=0.012] were found to be associated with DVT occurrence at 3 months after surgery. The area under the curve (AUC) for predicting DVT three months after hip or knee arthroplasty was 0.803 [95% CI (0.761, 0.844)]. Conclusion:Advanced age, female gender, history of previous thrombotic diseases, occurrence of DVT on the first day after surgery, and surgery in autumn are risk factors for DVT occurring 3 months after joint replacement surgery.

Osteoarthritis (OA), in which M1 macrophage polarization in the synovium exacerbates disease progression, is a major cause of cartilage degeneration and functional disabilities. Therapeutic strategies of OA designed to interfere with the polarization of macrophages have rarely been reported. Here, we report that SHP099, as an allosteric inhibitor of src-homology 2-containing protein tyrosine phosphatase 2 (SHP2), attenuated osteoarthritis progression by inhibiting M1 macrophage polarization. We demonstrated that M1 macrophage polarization was accompanied by the overexpression of SHP2 in the synovial tissues of OA patients and OA model mice. Compared to wild-type (WT) mice, myeloid lineage conditional Shp2 knockout (cKO) mice showed decreased M1 macrophage polarization and attenuated severity of synovitis, an elevated expression of cartilage phenotype protein collagen II (COL2), and a decreased expression of cartilage degradation markers collagen X (COL10) and matrix metalloproteinase 3 (MMP3) in OA cartilage. Further mechanistic analysis showed thatSHP099 inhibited lipopolysaccharide (LPS)-induced Toll-like receptor (TLR) signaling mediated by nuclear factor kappa B (NF-κB) and PI3K-AKT signaling. Moreover, intra-articular injection of SHP099 also significantly attenuated OA progression, including joint synovitis and cartilage damage. These results indicated that allosteric inhibition of SHP2 might be a promising therapeutic strategy for the treatment of OA.

【Objective】 To establish the reference interval of Thromboelastography(TEG)of healthy adult in Hainan, compare with the interval provided by the manufacturers, and analyze the influencing factors. 【Methods】 A total of 308 healthy adult volunteers were included according to the inclusion and exclusion criteria. The TEG was analyzed based on adequate quality control, and the reference interval of each parameter was calculated with 95% CI. 【Results】 The reference interval of these volunteers were R 4.27~9.20 min, K 1.60~3.83 min, Angle 44.22°~67.78°, MA 47.82~64.17 mm, CI -5.63~1.12 and G 4.58~9.03. 14.94% (46/308) of these volunteers had at least one index exceeded the reference interval provided by manufacturers. A total of 74 healthy volunteers were diagnosed with coagulation disorder, with the specificity at 79.22%. Significant differences of R, K, Angle, MA, CI, G were observed between males and females (P<0.05). Hypercoagulability was not associated with the age. 【Conclusion】 This study established a reference interval of TEG of healthy adults in Hainan, which provided reference for related clinical and basic science study.

【Objective】 To investigate the correlation between preoperative thromboelastography (TEG) parameters and routine coagulation tests of malignant tumor patients. 【Methods】 A total of 79 patients with malignant tumors, receiving preoperative TEG tests and routine coagulation tests between January 2019 and June 2020, were included. The correlation and regression between coagulation indexes and TEG parameters were analyzed. 【Results】 In patients with malignant tumors, the coagulation time(K) was negatively correlated with Plt and fibrinogen (FIB), while Angle, Ma, and G were respectively positively correlated with Plt and FIB. 【Conclusion】 There is a correlation between preoperative TEG parameters and routine coagulation tests in patients with malignant tumors. There is complementarity but not reciprocal substitutability between these two tests.

Objective:To explore the incidence and risk factors of preoperative deep vein thrombosis (DVT) of elective total joint arthroplasty (TJA).Methods:Data of 500 patients before TJA from March 2015 to August 2016 who underwent ultrasound surveillance were retrospectively analyzed. All patients were divided into DVT group and non-DVT group according to results of ultrasound. Parameters including demographic data, basic medical history, and surgical information and laboratory indexes were collected. Risk factors were assessed via univariate, multivariate and logistic regression analysis.Results:Preoperative DVT was detected in 23 cases (4.6%, 23/500), all of which occurred in the intermuscular vein with no symptom, and among them there were 16 cases (5.6%, 16/285) before total knee arthroplasty and 7 cases (3.3%, 7/215) before total hip arthroplasty. Univariate analysis showed that age ( t=2.266, P=0.024), female patients ( χ2=4.028, P=0.045), history of hypertension ( χ2=7.907, P=0.005), D-dimer ≥0.5 μg/ml ( χ2=13.171, P < 0.001) were significantly higher than those in non-DVT group, and the differences were statistically significant. Multivariate analysis showed that D-dimer ≥0.5 μg/ml [ OR=6.655, 95% CI (1.929, 22.960), P=0.003] and history of hypertension [ OR=2.715, 95% CI (1.017, 7.250), P=0.046] were independent risk factors for preoperative DVT. Among them, the thrombus of 14 cases located in the operation side, 6 cases in non-operation side, and 3 cases in bilateral sides. Postoperative ultrasound showed that newly DVT occurred in 9 patients of whom 5 cases located in the contralateral muscular veins and 4 cases in the nearby muscular veins. After discharge, 22 patients (95.7%) with preoperative DVT were further evaluated by ultrasound. The average follow-up time was 3.0 months (range from 6 weeks to 9 months). The results showed that thrombus of 7 cases were completely dissolved, 13 cases were partially dissolved, and 2 cases remained unchanged. Thrombus extensions to proximal veins or symptomatic PE were not found. Conclusion:The incidence of preoperative DVT in patients with elective joint replacement was about 4.6%, among which D-dimer ≥0.5 μg/ml and history of hypertension were the risk factors for preoperative thrombosis.

Objective To find out if there is any difference in intercondylar fossa width and notch width index (NWI) between tibial intercondylar eminence avulsion fracture and anterior cruciate ligament (ACL) injury.Methods A retrospective study was conducted of the patients who had sought medical attention at Department of Sports Medicine and Adult Reconstructive Surgery,Drum Tower Hospital from June 2014 to May 2018.There were 10 patients with tibial intercondylar eminence avulsion fracture (4 males and 6 females with an average age of 32.7 ± 9.2 years),13 patients with ACL injury (8 males and 5 females with an average age of 31.8 ± 10.9 years) and 22 patients with simple meniscus injury as controls (13 males and 9 females with an average age of 30.9 ± 10.6 years).They all had MRI examination of the knee before surgery.The width of intercondylar fossa and the width and height of bilateral femoral condyles were measured on high resolution images of MRI axial view.NWI was calculated.The 3 groups were compared in intercondylar fossa width and NWI.Results The 3 groups of patients were comparable because there were no significant differences in gender,age,height,weight or BMI between them (P ＞ 0.05).The intercondylar fossa width in the ACL injury group (17.4 ± 3.5 mm) was significantly smaller than that in the avulsion fracture group (20.8 ± 1.1 mm) or in the control group (20.2 ±2.6 mm) (P ＜ 0.05),but no significant difference was detected between the avulsion fracture group and the control group (P ＞ 0.05).NWI in the avulsion fracture group (0.301 ±0.011) was similar to that in the control group (0.280 ±0.039) (P ＞ 0.05) but significantly higher than that in the ACL injury group (0.25 ± 0.05) (P ＜ 0.05).NWI in the ACL injury group was significantly lower than that in the control group (P ＜ 0.05).Conclusions Intercondylar notch stenosis may be a risk factor for ACL injury but may not be associated with tibial intercondylar eminence avulsion fracture.The difference in pathogenesis between tibial intercondylar eminence avulsion fracture and ACL injury may be associated with their difference in NWI.

Objective To evaluate the feasibility of anticoagulant therapy for acute proximal deep vein thrombosis without inferior vena cava filter placement for femoral neck patients before hip arthroplasty.Methods From January 2013 to August 2017,9 femoral neck fractures patients with acute proximal deep vein thrombosis before hip arthroplasty were enrolled into this study.There were 3 men and 6 women.The average age was 76.44±5.39 years old (range,69 to 83 years old).The average injured time before admission was 4.00±4.06 days.All patients received anticoagulant therapy without placement of inferior vena cava filter before hip arthroplasty.Four patients received Rivaroxaban 10mg,two times per day,while two patients received Enoxaparin 0.4 ml,two times per day;3 cases received Batroxobin 0.5 ml,every other day combined with Rivaroxaban 10 mg one time per day or Enoxaparin 0.4 ml,one time per day.The size of thrombus before and after treatment,changes of coagulation markers,the outcome of thrombosis before surgery,during surgery,postoperatively and during follow-up,the related complications were recorded.Results The diagnosis time for proximal DVT was 3.89±3.01 days after admission.8 patients showed proximal DVT combined with distal thrombus and 1 patient showed isolated proximal DVT.The average length of proximal thrombus was 10.78±6.10 cm (range,4.0-20.0 cm).The mean duration of treatment was 14.22±7.03 days.The results showed 5 proximal DVTs have complete disappeared,3 cases significantly improved,and 1 case had no change but showed stable.After treatment,the length of the proximal thrombus was significantly decreased (10.77±6.10 cm vs.4.39±6.50 cm),there were statistically significant between two groups (t=3.429,P=0.009);D-dimer was significantly lower after treatment (10.47±4.87 μg/ml vs.2.59± 1.60 μg/ml) with statistical difference (t=4.970,P=O.O01).However,no statistical significance was found in other coagulation parameters such as plasma prothrombin time,the international normalized ratio,activated partial thromboplastin time,thrombin time,fibrinogen.Incision exudate occurred in one patient and anticoagulant therapy was paused,however,two days later,DVT recurred and then the patient received continuous therapy with drug anticoagulation.The average time for postoperative follow-up was 8.3±7.6 months.At the latest follow-up,4 cases had thoroughly recovered with the thrombi fully resolved;4 cases had significantly improved including three thrombi partly locating in the muscular veins and one partly locating in the infra-popliteal vein.One case became more severe after discharge and received continuous anticoagulant therapy.No death,symptomatic pulmonary embolism,bleeding and other adverse events occurred.Conclusion Inferior vena cava filter placement for femoral neck fracture patients with acute proximal venous thrombosis before hip arthroplasty may not be potent.Anticoagulant therapy which make the proximal thrombus completely dissolved or stabilized before surgery may be effective.