【Abstract】 Objective To investigate the effect of retinoic acid (RA) on cell apoptosis and gene regulation of IGF-2in chondrocyte. Methods One 1-month-old Chinese rabbit weighted 500 g was used in this experiment. The chondrocyte from rabbit knee were cultured by enzyme digestion. Twenty-five μL all-trans-retinoic acid (ATRA) (1×10-6 mol/L) were added in the media of cultured chondrocyte for 24 hours as experimental group, while 25 μL DMEM were added as control group. The secretion of collagen Ⅱ was observed by immunohistochemistry method, cell apoptosis was detected by flow cytometry, IGF-2 mRNA and protein expression in chondrocyte were detected by RT-PCR and Western blot analysis. Results The expression of collagen Ⅱ was down-regulated by ATRA in the experimental group. The cell apoptosis in chondrocyte exposed to ATRA at 1 ×10-6 mol/L was 21% ± 2%, which increased 5 times compared with the control group（5% ± 1%）. The IGF-2 mRNA and protein level in the experimental group were decreased 75% and 57%, respectively, compared to the control group. There weresignificant difference between the experimental group and control group in each index (P lt; 0.05). Conclusion RA may down-regulate the secretion and cell prol iferation, but up-regulate the cell apoptosis in chondrocyte. The apoptotic effect may carry out through inhibiting the IGF-2 expression of chondrocyte.
Objective To evaluate the long-term anticoagulation outcomes of target international normalized ratio (INR) 1.60 to 2.20 and weekly dosage adjustment of warfarin in patients after mechanical heart valve replacement. Methods Outpatients after mechanical heart valve replacement at least 6 months were registered continually from July 2011 to July 2016 in department of cardiothoracic surgery at Zigong No.4 People's Hospital and West China Hospital. There were 1 690 females (70.62%) and 703 males (29.38%) with a median age of 47 years, ranging from 14 to 80 years. All patients were followed up for 6-61 months. Target INR was 1.60 to 2.20 and warfarin dosage were adjusted weekly. Unexpected bleeding, thrombogenesis and thromboembolism, time in therapeutic range (TTR) and fraction of TTR (FTTR) were recorded and calculated to evaluate the outcome of anticoagulation management. Results A total of 2 393 patients with 26 521 INR values were included for data analysis. INR values varied from 0.90-8.39 (1.82±0.45) and required weekly doses of warfarin were 1.75-61.25 (21.72±7.39) mg. TTR of target INR and acceptable INR was 59.38% (1 449 514.0 days/2 441 060.0 days) and 73.57% (1 795 971.0 days/2 441 060.0 days), respectively. FTTR of target INR and acceptable INR were 50.71% (13 450 times/26 521 times), 65.25% (17 305 times/26 521 times). During the follow-up , anticoagulation-related complications included: cerebral infarction in 21 patients (complete recovery in 18 patients, physical activity disorder in 3 patients), cerebral hemorrhage in 4 patients (death in 1 patient, complete recovery in 3 patients), severe gastrointestinal bleeding in 3 patients (completely recovered) and uterine bleeding in 1 patient (surgical removal of the uterus). Conclusion Target INR 1.60–2.20 and warfarin weekly dosage adjustment for patients after mechanical heart valve replacement is reasonable and safe.
ObjectivesTo evaluate the efficacy and safety of four antiplatelet regimens after coronary drug-eluting stents by network meta-analysis.MethodsPubMed, The Cochrane Library, EMbase and Web of Science databases were electronically searched to collect randomized controlled trials (RCTs) of the comparison of different antiplatelet regimens after coronary drug-eluting stenting from inception to December 31st, 2019. Two reviewers independently screened literature, extracted data and assessed risk bias of included studies. Network meta-analysis was then performed by using Gemtc14.3 software, Stata16.0 software and RevMan5.3 software.ResultsA total of 23 RCTs involving 45 837 patients were included. The results of network meta-analysis showed that: in terms of prevention of myocardial infarction (MI) recurrence, the aspirin monotherapy after short-term dual antiplatelet therapy was inferior to the triple antiplatelet therapy (OR=2.13, 95%CI 1.08 to 4.03). In terms of reducing the incidence of ischemic compound events, the triple antiplatelet therapy was superior to the standard dual antiplatelet therapy (OR=0.53, 95%CI 0.39 to 0.72), the aspirin monotherapy after short-term dual antiplatelet therapy (OR=0.49, 95%CI 0.35 to 0.69) and the P2Y12 inhibitor monotherapy after short-term dual antiplatelet therapy (OR=0.51, 95%CI 0.35 to 0.73). There was no statistically significant difference among the four interventions in reducing the rate of in-stent thrombosis and all-cause mortality (P>0.05). In terms of safety, the bleeding rate of aspirin monotherapy after short-term dual antiplatelet therapy was lower than that of standard dual antiplatelet therapy (OR=0.70, 95%CI 0.55 to 0.86) and triple antiplatelet therapy (OR=0.58, 95%CI 0.36 to 0.90), and the bleeding rate of P2Y12 inhibitor monotherapy after short-term dual antiplatelet therapy was also lower than that of standard dual antiplatelet therapy (OR=0.51, 95%CI 0.39 to 0.65) and triple antiplatelet therapy (OR=0.43, 95%CI 0.26 to 0.67). The probability ranking diagram showed that: in terms of the recurrence rate of MI, the rate of in-stent thrombosis and the incidence of ischemic compound events, triple antiplatelet therapy was the lowest and aspirin monotherapy after short-term dual antiplatelet therapy was the highest. However, in terms of all-cause mortality and bleeding rate, aspirin or P2Y12 inhibitor monotherapy after short-term dual antiplatelet therapy was the lowest and triple antiplatelet therapy was the highest.ConclusionsThe available evidence suggests that when the risk of ischemia is low, we should choose aspirin or P2Y12 inhibitor monotherapy after short-term dual antiplatelet therapy, and P2Y12 inhibitor monotherapy may have a lower risk of ischemia and bleeding. When the risk of ischemia is high and bleeding is low, the triple or standard dual antiplatelet therapy should be selected, and the efficacy of triple antiplatelet therapy is superior, while the safety may be inferior.
Abstract： Objective To investigate diagnosis and treatment of concealed intrathoracic anastomotic leak of the esophagus. Methods We retrospectively analyzed the clinical data of 32 patients who presented with unexplained sepsis （temperature＞38 ℃ and elevated white blood cell count） after esophagectomy and intrathoracic anastomosis for esophageal carcinoma or gastric cardia carcinoma in Affiliated Hospital, Medical College of Qingdao University from January 2006 to December 2010. All the patients underwent oral water-soluble contrast esophagogram and oral water-soluble contrast computerized tomography of the chest. None of the patients had any sign of contrast leak in these diagnostic examinations, but their chest computerized tomography all showed peri-anastomotic bubble and encapsulated effusion. Fifteen patients were treated as concealed intrathoracic anastomotic leak of the esophagus, including fasting, broad spectrum antibiotic treatment, prolonged gastrointestinal decompression and enteral nutrition via naso-intestinal feeding tube. The other 17 patients were not treated as anastomotic leak of the esophagus and only received broad spectrum antibiotic treatment. Results None of the 15 patients who were treated as concealed intrathoracic anastomotic leak finally developed anastomotic leak proved by oral water-soluble contrast esophagogram and computerized tomography of the chest （0%, 0/15）. Among the 17 patients who were not treated as anastomotic leak, fourteen patients developed anastomotic leak later （82.4%, 14/17）, 2 patients died of aorto-esophageal fistula and 3 patients died of multiple organ dysfunction syndrome. Conclusion Peri-anastomotic bubble and irregular encapsulated effusion in oral water-soluble contrast esophagogram and computerized tomography of the chest should be considered as specific signs of concealed intrathoracic anastomotic leak of esophagus after esophagectomy and intrathoracic anastomosis. Patients with such signs should be treated as anastomotic leak.
ObjectiveTo investigate the effect of Masquelet technique combined with artificial dermis on repairing bone and soft tissue defects in rabbits, and to observe the microstructure and vascularization of induced membrane, so as to guide the clinical treatment of Gustilo-Anderson type Ⅲ open fracture with large bone defect and soft tissue defect.MethodsEighty male rabbits, weighing 2.03-2.27 kg (mean, 2.11 kg), were selected. The bilateral thighs of 64 rabbits were randomly divided into experimental group and control group, the remaining 16 rabbits were sham operation group. Bone and soft tissue defect models of femur were made in all rabbits. In the experimental group, the first stage of Masquelet technique was used [polymethyl methacrylate bone cement was filled in bone defect area] combined with artificial dermis treatment; in the control group, the first stage of Masquelet technique was used only; in the sham operation group, the wound was sutured directly without any treatment. Four rabbits in sham operation group and 16 rabbits in the experimental group and control group were sacrificed at 2, 4, 6, and 8 weeks after operation, respectively. The induced membranes and conjunctive membranes were observed on both sides of the femur. The membrane structure was observed by HE staining, and the microvessel density (MVD) was counted by CD34 immunohistochemical staining.ResultsGross observation showed that the spongy layer of collagen in the artificial dermis of the experimental group disappeared completely at 4 weeks after operation, and the induced membrane structure of the experimental group and the control group was complete; the membrane structure of the control group was translucent, and the membrane structure of the experimental group was thicker, light red opaque, accompanied by small vessel proliferation. The membrane structure of the experimental group and the control group increased gradually from 6 to 8 weeks after operation. In the sham operation group, only scar tissue proliferation was observed over time. HE staining showed that a large number of muscle fibers and a small amount of collagen fibers proliferation with inflammatory cell infiltration could be seen in the experimental group and the control group at 2 weeks after operation; most of the sham operation group were muscle fibers with a small amount of interfibrous vessels. At 4 weeks after operation, collagen fibers increased and some blood vessels formed in the experimental group. The nuclei of collagen fibers in the control group were round-like, while those in the experimental group were flat-round. At 6 and 8 weeks after operation, the collagen fibers in the experimental group and the control group increased. The nuclei of the collagen fibers in the control group were still round-like. The nuclei of the collagen fibers in the experimental group were fusiformis and deeply stained compared with those in the control group. The proliferation of blood vessels was observed in both groups, and the number of proliferation vessels in the experimental group was increased compared with that in the control group. In the sham operation group, a large number of fibroblasts still appeared, but no significant proliferation of blood vessels with time was observed. CD34 immunohistochemical staining showed that MVD in each group increased gradually with the prolongation of time after operation. MVD in the sham operation group was significantly higher than that in the experimental group and the control group at 2 weeks after operation, and significantly smaller than that in the experimental group and the control group at 4, 6, and 8 weeks after operation (P<0.05). MVD in the experimental group was significantly higher than that in the control group at 4 and 6 weeks after operation (P<0.05), but there was no significant difference in MVD between the two groups at 2 and 8 weeks (P>0.05).ConclusionMasquelet technique combined with artificial dermis in the treatment of femoral bone defect and soft tissue defect in rabbits can significantly promote the vascularization of membrane structure at 4-6 weeks after operation. The combination of these two methods has guiding significance for the treatment of Gustilo-Anderson type Ⅲ open fracture with bone and soft tissue defects.