miR-21-3p regulates AGE/RAGE signalling and improves diabetic atherosclerosis.

To explore the effects of miR-21-3p on diabetic atherosclerosis. Using enzyme-linked immunosorbent assay (ELISA), we also detected the levels of soluble receptor for advanced glycation endproducts RAGE (sRAGE) in the cellular supernatant of vascular endothelial cells after transfecting them with adenovirus vector having miR-21-3p mimic or inhibitor. We found decrease in the expression levels of miR-21-3p in vascular endothelial cells (VECs) induced by high-concentration glucose. We also observed that the introduction of miR-21-3p mimic significantly increased the expression of ADAM10 in the VECs. Similarly, significantly higher levels of sRAGE were found in the cultured supernatant after administration of miR-21-3p mimic in human vein endothelial cells. The production of reactive oxygen species and expression of inflammatory cytokines in VECs induced by LPS and high-concentration glucose were significantly decreased after administration of miR-21-3p. in vivo studies revealed that intravenous injection of miR-21-3p at regular intervals would reduce the area of atherosclerotic lesion and elevate the serum levels of sRAGE in atherosclerotic diabetic mice. miR-21-3p may be beneficial in diabetic atherosclerosis by promoting the cleaved form of sRAGE and inhibition of RAGE/NADPH oxidase signalling depending on the increased expression of ADAM10. SIGNIFICANCE OF THE STUDY: We identified a novel microRNA, miR-21-3p, which is characteristically at elevated levels in serum derived from diabetic patients and responsible for target degradation of ADAM10 mRNA. Further, we show that miR-21-3p aggravates the atherosclerotic lesion via dysfunction of the ectodomain shedding of molecular binding RAGE in the diabetic atherosclerotic mice.

Investigation of the Incidence of Perioperative Pulmonary Embolism in Patients with Below-Knee Deep Vein Thrombosis after Lower Extremity Fracture and Evaluation of Retrievable Inferior Vena Cava Filter Deployment in These Patients.

BACKGROUND: The objectives of the study were to investigate and compare the incidence of perioperative pulmonary embolism (PE) in trauma patients with below-knee deep vein thrombosis (BKDVT) and above-knee DVT (AKDVT) who need major orthopedic surgery and evaluate the usage of inferior vena cava (IVC) filters in these cases with BKDVT. METHODS: Between January 2003 and December 2017, patients with pelvic and/or lower extremity fracture diagnosed with DVT by duplex ultrasound were eligible for the study. A reduced-dose anticoagulation therapy was administered in patients without absolute contraindication to anticoagulation therapy during the perioperative period. Patients who did not undergo filter insertion with BKDVT were classified as the BKDVT group, and cases with thrombosis involving the popliteal or more proximal veins were classified as the AKDVT group; the incidence of PE was analyzed. Among patients with BKDVT, cases with or without filter deployment were placed in the filter group and control group, respectively, to evaluate the value of IVC filter in these patients. RESULTS: A total of 3295 patients with pelvic and/or lower extremity fracture were diagnosed as having DVT, among which, 2070 cases did not undergo filter insertion. The incidence of PE in the BKDVT group and AKDVT group was 2.08% (24/1154) and 3.17% (29/916), respectively. A total of 366 patients with BKDVT underwent filter placement and no PE occurred. The incidence of PE in the filter group was lower than the control group. In patients without filter placement, the cases received anticoagulation therapy and those who did not, the incidence of PE was 2.21% and 1.94%, respectively, and there was no difference between the two subgroups. CONCLUSIONS: There was no difference in incidence of PE between the AKDVT and BKDVT groups. Reduced-dose anticoagulation therapy does not affect the rates of PE in trauma patients with BKDVT who require ongoing orthopedics operations. For these patients, placement of the retrievable filter may be considered.

An Automatic Classification Method on Chronic Venous Insufficiency Images.

Chronic venous insufficiency (CVI) affect a large population, and it cannot heal without doctors' interventions. However, many patients do not get the medical advisory service in time. At the same time, the doctors also need an assistant tool to classify the patients according to the severity level of CVI. We propose an automatic classification method, named CVI-classifier to help doctors and patients. In this approach, first, low-level image features are mapped into middle-level semantic features by a concept classifier, and a multi-scale semantic model is constructed to form the image representation with rich semantics. Second, a scene classifier is trained using an optimized feature subset calculated by the high-order dependency based feature selection approach, and is used to estimate CVI's severity. At last, classification accuracy, kappa coefficient, F1-score are used to evaluate classification performance. Experiments on the CVI images from 217 patients' medical records demonstrated superior performance and efficiency for CVI-classifier, with classification accuracy up to 90.92%, kappa coefficient of 0.8735 and F1score of 0.9006. This method also outperformed doctors' diagnosis (doctors rely solely on images to make judgments) with accuracy, kappa and F1-score improved by 9.11%, 0.1250 and 0.0955 respectively.

Heparan sulfate inhibits inflammation and improves wound healing by downregulating the NLR family pyrin domain containing 3 (NLRP3) inflammasome in diabetic rats.

BACKGROUND: Heparan sulfate (HS) attenuates the inflammatory response and improves diabetic wound healing in rats. However, the specific mechanisms by which HS suppresses inflammation are not clear. Given that NLR family pyrin domain containing 3 (NLRP3) is a major receptor involved in innate immune regulation, the aim of the present study was to elucidate the effects of HS on NLRP3 and proinflammatory cytokines in diabetic wounds. METHODS: Full-thickness wounds were created on the back of diabetic rats. The experimental group received HS treatment (1 mg/kg, i.m., on Days 0 and 7), whereas the control group received vehicle (0.1% dimethylsulfoxide in 0.9% NaCl). Expression of NLRP3 and its downstream effector molecules, namely cleaved interleukin (IL)-1ß, IL-18, tumor necrosis factor (TNF)-α, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), proteinase inhibitor 9, and caspase-12, in the wound tissues was examined. RESULTS: Treatment with HS accelerated wound healing in diabetic rats. Rats treated with HS exhibited decreased activation of cleaved IL-1ß, IL-18, and TNF-α, as well as decreased expression of NLRP3 and ASC. In addition, HS increased levels of proteinase inhibitor 9 and caspase-12. CONCLUSIONS: Heparan sulfate inhibits inflammation and improves wound healing by downregulating the NLRP3 inflammasome and cleaved IL-1ß during the wound healing process in diabetic rats.

Evaluation of nonpermanent inferior vena cava filter placement in patients with deep venous thrombosis after lower extremity fracture: A single-center retrospective study.

OBJECTIVE: To investigate nonpermanent inferior vena cava (IVC) filter in the prevention of perioperative pulmonary embolism (PE) in patients of lower extremity and/or pelvic bone fracture with deep vein thrombosis (DVT). METHODS: Lower extremity or pelvic bone fracture patients with lower extremity DVT hospitalized in our hospital from January 2003 to October 2014 were retrospectively analyzed. Data was analyzed for age, gender, position of fracture, position of proximal of thrombosis, indications of placement, complications, retrieval rate, and rate of entrapped filter clot. Patients who underwent IVC filter placement were selected as the filter group. The patients who did not perform IVC filter placement after 2008 and the cases between January 2003 and December 2007 were selected as control group 1 and control group 2, respectively. The incidence of perioperative symptomatic PE and mortality were analyzed. RESULTS: A total of 2763 cases complicated with DVT underwent orthopedic surgery between January 2003 and October 2014. 823 nonpermanent filters were inserted. All filters were successfully deployed with no major complications. After a mean 14.2 days indwelling time, all of temporary filters were removed. Retrieval was attempted in 556 patients with retrievable filters and was successful in 545 (98%); mean indwelling time was 16.3 days. The total retrieval rate was 90%. The incidence of PE in the filter group was significantly lower compared with the two control groups. Among the patients who received chemical anticoagulant therapy, the incidence of PE in filter group, control group 1 and control group 2 were 0.14%, 1.60% and 2.10%, respectively. The incidence of PE in filter group was also significant lower compared with control groups. CONCLUSION: Nonpermanent IVC filter placement seems like to be a safe and effective method for preventing perioperative symptomatic and fatal PE in bone fracture patients with DVT in the present retrospective study.

Calcium alginate enhances wound healing by up-regulating the ratio of collagen types I/III in diabetic rats.

Calcium alginate has been proved to favor the skin ulcer healing and collagen synthesis was a critical factor for the wound closure. The present study was to elucidate the mechanism of calcium alginate on the diabetes skin ulceration. Calcium alginate dressing was applied daily on the full-thickness exercising wound created on the back of diabetic rat model as Alg-group (n=6), and the vaseline dressing was used as control (n=6). Rats were respectively sacrificed and the wound tissues were removed and used for the evaluation of various biochemical analysis contained collagen (type I and III) by Western blotting and hydroxyproline level changes by ELISA assay at 3 d, 7 d and 14 d after wounding. The expression of skin collagen I in Alg-group was enhanced from day 3 (0.66 ± 0.25 vs. 0.42 ± 0.09, P<0.05) to day 14 (1.09 ± 0.14 vs. 0.78 ± 0.16, P<0.05). However, no significant difference of collagen III expression was found between two groups during wound healing (P>0.05). And the ratio of collagen I/III in Alg-group was greater than that of Vas-group at day 7 (1.07 ± 0.31 vs. 0.77 ± 0.11, P<0.05) and 14 (1.18 ± 0.30 vs. 0.83 ± 0.14, P<0.05). The hydroxyproline level in skin homogenate of Alg-group was higher than that of Vas-group from day 3 (30.29 ± 0.92 ng/ml vs. 27.52 ± 0.83 ng/ml, P<0.05) to day 14 (89.58 ± 4.97 ng/ml vs. 79.30 ± 4.42 ng/ml, P<0.05). Calcium alginate accelerates the process of wound healing through improving type I collagen synthesis and increasing ratio of collagen I/III in diabetic rats.

[A single-center retrospective study on the intraluminal implantation of inferior vena cava filter for the lower extremity trauma patients with deep venous thrombosis].

OBJECTIVE: To evaluate the application of inferior vena cava filter (IVCF) in prevention of peri-operative pulmonary embolism (PE) in lower limb bone fracture patients with deep venous thrombosis (DVT). METHODS: From January 2003 to December 2012, 2 248 cases of lower limb and pelvic fractures with DVT were retrospectively analyzed. Before the procedure of IVCF implantation began, January 2003 to December 2007, there were 1 052 cases of acute trauma patients with DVT were classified as the group of early none-IVCF. The IVCF implantation was began since January 2008. From that time to December 2012, 712 cases of bone fractures with DVT received filter implantation, which were classified as IVCF group. The other 484 patients who had not undergone filter deployment were divided as group of late none-IVCF. The baseline conditions of the three groups were significantly different in addition to the ages between group of early none-IVCF and IVCF group. The incidences of PE and mortality of PE in each group were recorded and analyzed by χ(2) test. RESULTS: There were totally 31 cases of symptomatic PE, among which 12 cases died. Totally 712 filters were deployed successfully without any major complications. The incidences of symptomatic PE were 0.14% (1/712), 2.19% (23/1 052) and 1.45% (7/484) in IVCF group, group of early none-IVCF and group of late none-IVCF, respectively. The mortality of PE were 0 (0/712), 0.86% (9/1 052) and 0.62% (3/484) in these groups. The incidence of symptomatic PE in IVCF group was significantly different from that in the group of early and late none-IVCF (χ(2) = 11.762, P = 0.001; χ(2) = 7.395, P = 0.007, respectively). The mortality of IVCF group was also significantly lower compared with the other two groups (χ(2) = 6.122, P = 0.013; χ(2) = 4.424, P = 0.035, respectively). CONCLUSION: IVCF implantation effectively prevents symptomatic and fatal PE of patients of lower limb and pelvic fractures with DVT in the peri-operative period.

[Combined use of occluder plus bare stent in the treatment of aortic dissection with tear at the area of visceral branches].

OBJECTIVE: To evaluate the novel method of combinedly use of occluder and bare stent in the treatment of aortic dissection with distal tear at visceral branches. METHODS: From April 2010 to September 2012, 6 patients (5 male and 1 female patients, aged from 29 to 62 years, mean 47.2 years) were diagnosed as Stanford type B aortic dissection that been revealed by CT angiography. The main tears were sealed with stent-grafts firstly, and then the tears at the visceral branch area were evaluated that impossible to close spontaneously. Atrium septal defect occluder and ventricular septal defect were implanted at the tears with the anterior disc in false lumen, while the posterior disc in the true lumen. After that, the bare stents were implanted in the true lumen to pull the occluders on the aortic wall. RESULTS: Among the 6 procedures, occluders were successfully implanted in 5 cases, and 1 failed anchoring at the tear, and the alternative method of coils embolization was applicated. After all the procedures, the immediate aortogrophy revealed that the false lumen disappeared in the 5 cases that occluders were used, and the visceral branches were all patent. No paraplegia, lesion of visceral organs or other complications occurred. All the cases were followed at least 5 months. There was one endoleak due to a non-sealed tear at the descending aorta, one new-occurred small tear in the descending aorta but with no communication to the false lumen. CONCLUSIONS: The combinedly use of occluder and bare stent in the treatment of aortic dissection with tears at the visceral branch area is a sum of two simple technique plus each other. It is easily to master. The lesions at the aortic that ordinary stent-grafting incapable to seal are successfully solved then. The huge trauma of open or hybrid procedures are avoided.

[Application of inferior vena cava filters in prevention of peri-operative pulmonary embolism in patients with bone fracture combined with deep venous thrombosis: a report of 572 cases].

OBJECTIVES: To evaluate the application of inferior vena cava filter (IVCF) in prevention of peri-operative pulmonary embolism in patients with bone fracture combined with deep venous thrombosis (DVT). METHODS: From July 2007 to April 2011, 572 cases of bone fractures consequent with DVT that confirmed by Duplex were deployed IVCF to avoid fatal pulmonary embolism in the para-operative period. There were 318 male and 254 female patients with a mean age of (51±23) years (ranging from 16 to 94 years). RESULTS: All the operations of deployment of the IVCFs were successfully. There were 174 permanent and 399 temporary IVCFs deployed. In all 399 temporary filters, 389 filters were taken out successfully. The mean station time in the IVC of the temporary filters was 22.8 days (7 to 60 days), among which, 118 were found of captured thrombus. After the follow-up of mean 16 months (3 to 40 months) of 566 patients, no pulmonary embolism occurred, but symptomatic DVT were revealed in 15 patients, and the conditions were improved after anticoagulation treatment. No serious complication of post thrombotic syndrome occurred. CONCLUSION: IVCF deployment can prevent the trauma patients with deep vein thrombosis of fatal pulmonary embolism in the peri-operative period, which may also offer a safe condition to the orthopedic operations.