ADAM10 attenuates the development of abdominal aortic aneurysms in a mouse model.

An abdominal aortic aneurysm (AAA) is a life­threatening disease associated with a high mortality rate. At present, surgery or minimally invasive interventions are used in clinical treatment, especially for small aneurysms. However, the benefits of surgical repair are not obvious, and AAA ruptures can be prevented by aneurysm therapy to inhibit the growth of small aneurysms. Therefore, evaluating effective drugs to treat small AAAs is urgently required. Chronic inflammation is the main pathological feature of aneurysmal tissues. The aim of the present study was to investigate the protective role and underlying mechanism of ADAM metallopeptidase domain 10 (ADAM10). In the present study, a mouse model of AAA was established via porcine pancreatic elastase perfusion for 5 min per day for 14 days. ADAM10 (6 mg/kg) was injected intraperitoneally following 3 days of porcine pancreatic elastase perfusion in the ADAM10 group and the treatment continued for 10 days. The maximum inner luminal diameters of the infrarenal abdominal aortas were measured using an animal ultrasound system. The levels of high mobility group box 1 (HMGB1) and soluble receptor for advanced glycosylation end products in serum samples were measured by ELISA. Hematoxylin and eosin and elastin van Gieson staining were performed to observe morphology, integrity of the elastin layers and elastin degradation. CD68 expression was detected by immunohistochemical staining. Reverse transcription­quantitative PCR and western blotting were used for detection of mRNA and protein levels. The gelatinolytic activities of MMP­2 and MMP­9 were quantified via gelatin zymography analysis. These results showed that ADAM10 inhibited HMGB1/RAGE/NF­κB signaling and MMP activity in the pathogenesis of pancreatic elastase­induced AAA, which provide insight into the molecular mechanism of AAA and suggested that ADAM10 may be a potential therapeutic target for AAA.

Percutaneous mechanical thrombectomy for the treatment of acute limb ischemia / 中华普通外科杂志

Objective:To analyze the application value of the mechanical thrombectomy system in the treatment of acute limb ischemia.Methods:The clinical data of 50 patients with lower limb ischemia who were treated with the Rotarex mechanical thrombectomy system from Jun 2017 to Sep 2019 were retrospectively analyzed.Results:In 4 cases of popliteal artery rupture occurred during the operation. The success rate of the operation was 92%. Catheter-directed thrombolysis was used in 7 cases, percutaneous transluminal angioplasty was used in 4 cases and percutaneous transluminal angioplasty combined with stent implantation was used in 39 cases. The ankle-brachial index of these 50 patients before and after operation was 0.18±0.24 and 0.64±0.28 respectively ( t=12.87, P<0.001). Treatment was successful in 43 cases. Follow-up ranged from 1 to 24 months, 5 cases were amputated, 2 cases had no improvement of toe ulcer gangrene, 9 cases had thrombus recurrence, and no complications such as bleeding were observed. The primary patency rates at 3, 6 and 12 months were 92%, 84% and 74%, respectively. Conclusion:The mechanical thrombectomy system is safe and effective in the treatment of acute lower limb ischemia with ideal short-term patency.

Gene transfer of human ANGPTL4 mediated by recombinant retroviral vector inhibits the growth of liver cancer / 中国普通外科杂志

Objective To construct recombinant retroviral vector containing human hepatocellular carcinoma-related gene ANGPTL4 ( angiopoietin-like 4) cDNA and to evaluate antitumor effect of recombinant retroviral vector-mediated human ANGPTL4 gene transfer. Methods ANGPTL4 cDNA was cloned in vitro from human liver cell lines HL-7702 and subcloned into plasmid vector pMSCV and sequenced. High-tiler recombinant retrovirus pMSCV-ANGPTLA and blank retrovirus pMSCV packaged under mediation of lipofectamine infected HepG2 cells in vitro, respectively. Flow cytometry and fluorescence microscopy detected expression of GFP (green fluorescence protein) in HepG2 cells. The expression of ANGPTL4 mRNA in HepG2 cells was determined. Results Recombinant retroviral vector pMSCV-ANGPTL4 was constructed successfully. Titer of recombinant retrovirus pMSCV-ANGPTL4 packaged is 1. 4 ? 106 infective viral grains /ml. Titer of blank retrovirus pMSCV packaged was 1. 5 ? 106 infective viral grains /ml. Positive cell rate of HepG2-ANGPTL4 cells group expressing GFP was 68.45% , and average intensity of fluorescence of HepG2-ANGPTL4 cells group was 31.67 -fold as that of HepG2 cells group. Positive cell rate of HepG2-pMSCV cells group expressing GFP was 77.72%, and average intensity of fluorescence of HepG2-pMSCV cells group was 64. 87 -fold as that of HepG2 cells group. The expression of ANGPTL4 mRNA in HepG2-ANGPTL4 cells group was higher than that in HepG2-pMSCV cells group (154%) and HepG2 cells group( 161%). The proliferation rate of HepG2-ANGPTL4 cells group in vitro was lower than HepG2-pMSCV cells group and HepG2 cells group (P

Dynamic changes of glucosylceramide synthase and caspase 3 in drug resistance induced by doxorubicin in human gallbladder carcinoma cell line GBC-SD / 中国病理生理杂志

AIM: To investigate the levels of mRNA, protein of glucosylceramide synthase (GCS) and caspase 3 in the drug resistance induced by doxorubicin in human gallbladder carcinoma cell line GBC-SD, the effect of ceramide metabolism in this process was examined. METHODS: Human gallbladder carcinoma cell line GBC-SD was treated by doxorubicin at concentration of 200 ?g/L for 12 weeks (named GBC-SD12). Cytotoxicity, mRNA and protein of GCS were measured on 1st week, 4th week and 12th week by MTT assays, RT-PCR or Western blotting. The levels of caspase 3 were measured by spectrofluorometry. RESULTS: A 3.8-fold increase in drug resistance to doxorubicin in GBC-SD12 was observed. Up-regulation of GCS mRNA and protein were also detected in GBC-SD12 (P