Apolipoprotein L Domain Containing 1 Inhibits Tissue Factor to Impede Thrombus Formation in a Rat Model of Deep Vein Thrombosis via Activating PI3K/Akt Pathway.

BACKGROUND: Deep venous thrombosis (DVT) is one of the major health problems worldwide. Apolipoprotein L domain containing 1 (APOLD1) was reported to be downregulated in DVT. The present study intended to investigate whether APOLD1 affects thrombus formation in a rat model of DVT. METHODS: The rat model of DVT was established by inferior vena cava (IVC) stenosis. At 6 hr, 12 hr, 24 hr, and 48 hr after IVC stenosis, the gross IVC with thrombus was dissected and observed. Then, the rats were preinjected with the lentiviral overexpression vector, APOLD1-LVs, 1 hr before IVC stenosis, to evaluate the influence of APOLD1 on thrombosis in rats. The serum levels of D-dimer and TAT as well as the content of TF in IVC tissues were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: IVC stenosis resulted in thrombus formation in rats, increased serum levels of D-dimer and TAT, and decreased APOLD1 expression. APOLD1 overexpression inhibited in vivo thrombosis, reduced serum levels of D-dimer, and downregulated tissue factor (TF) activity and level. APOLD1 overexpression also increased p-PI3K and p-Akt protein levels. CONCLUSIONS: APOLD1 suppresses thrombus formation in a rat model of DVT via downregulating TF expression by activating the PI3K/Akt pathway.

Drug-coated balloon angioplasty versus balloon angioplasty for treating patients with in-stent restenosis in the femoropopliteal artery: A meta-analysis.

BACKGROUND: The introduction of endovascular surgery has led to frequent stent use, although in-stent restenosis (ISR) remains a challenging issue. Drug-coated balloon (DCB) and conventional balloon angioplasty (BA) are common endovascular procedures for addressing ISR in the femoropopliteal artery. However, there is controversy regarding which procedure provides the greatest benefit to patients. METHODS: The PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched for prospective controlled trials that compared DCB and BA for patients with ISR in the femoropopliteal artery. The study has been approved by Ethics Committee of Wuhan Central Hospital. RESULTS: The meta-analysis included 6 prospective trials with 541 patients. We found that DCB use was associated with significant reductions in binary restenosis at 6 months (relative risk [RR]: 0.45, 95% confidence interval [CI]: 0.33-0.63; P < .00001), binary restenosis at 1 year (RR: 0.44, 95% CI: 0.34-0.57; P < .00001), target lesion revascularization (TLR) at 6 months (RR: 0.36, 95% CI: 0.20-0.65; P = .0006), and TLR at 1 year (RR: 0.38, 95% CI: 0.27-0.54; P < .00001). The DCB group also had significantly better clinical improvement (RR: 1.39, 95% CI: 1.13-1.71; P = .002), although we did not detect inter-group differences in terms of death, target vessel thrombosis, or ipsilateral amputation. The brand of DCB may a cause of heterogeneity. CONCLUSION: Relative to BA, DCB use increases the durability of treatment for ISR in the femoropopliteal artery, based on significant reductions in binary restenosis and TLR at 6-12 months after the procedure. Furthermore, DCB use was associated with better clinical improvement. However, additional randomized controlled trials are needed to validate these findings.

[Expression of vascular endothelial growth factor C in pancreatic cancer and its effect upon lymph node metastasis].

OBJECTIVE: To investigate the expression of vascular endothelial growth factor C (VEGF-C) and the effect of antisense oligonucleotide (ASODN) upon lymph node metastasis of pancreatic cancer cell. METHODS: We selected 15 cases of human pancreatic cancer and detected the expression of VEGF-C in primary tumor and lymph node metastasis tissues with immunohistochemistry. Meanwhile, the spontaneous lymphatic metastasis model in nude mice was established with orthotopic implantation for the human pancreatic cancer cell line PANC-1, isolation and culture of primary tumor and spontaneous lymphatic metastasis. The effect of VEGF-C special ASODN upon the apoptosis of pancreatic cancer cell derived from primary tumor and spontaneous lymphatic metastasis were detected by reverse transcription polymerase chain reaction (RT-PCR), enzyme linked immunosorbent assay (ELISA), flow cytometer and terminal deoxynucleotidyl transferase mediated-dUTP nick end labeling (TUNEL). RESULTS: In tissues of human pancreatic cancer, the values of VEGF-C on lymph nodes metastasis were more higher than primary tumor (P < 0.05). About the expression of VEGF-C on pancreatic cancer cell derived from spontaneous lymphatic metastasis and primary tumor in nude mice model, the mRNA levels of VEGF-C were 0.87 +/- 0.11 and 0.61 +/- 0.15 respectively, the VEGF-C levels in culture supernatants were (1682 +/- 157) pg/ml and (1404 +/- 128) pg/ml. The expression of VEGF-C on pancreatic cancer cells derived from lymphatic metastasis were also more higher than primary tumor (P < 0.05). In vitro and vivo, transfection of VEGF-C ASODN decreased the expression of VEGF-C in pancreatic cancer cell. In control group, scramble-sense oligonucleotide (SODN) group and ASODN group, the apoptosis rates of pancreatic cancer cells derived from lymph node metastasis were (2.8 +/- 1.0)%, (5.0 +/- 2.1)%, (13.2 +/- 2.2)% respectively in vitro, and were (1.8 +/- 0.5)%, (2.0 +/- 0.7)%, (4.4 +/- 1.0)% respectively in vivo, the apoptosis was increased significantly after transfection of VEGF-C ASODN (all P < 0.01). But pancreatic cancer cells derived from primary tumor were not effected (all P > 0.05). CONCLUSION: In human pancreatic cancer and nude mice model, the expression of VEGF-C on lymphatic metastasis was higher than primary tumor. The apoptosis of pancreatic cancer cells derived from spontaneous lymphatic metastasis were promoted by transfection of VEGF-C ASODN specially.

Combination of endovascular graft exclusion and drug therapy in AAA with hypertension or hyperglycemia.

BACKGROUND: The objective of the present study was to evaluate the efficacy of combination of endovascular graft exclusion and drugs for hypertension/hyperglycemia for the treatment of abdominal aortic aneurysm (AAA). METHODS: We analyzed 156 patients with AAA. Eighty-four patients were hypertensive and 72 were hyperglycemic. After endovascular graft exclusion, hypertensive patients were divided into four groups and treated with cyclopenthiazide, reserpine, propranolol, and placebo respectively. Hyperglycemic patients were divided into three groups and treated with metformin, insulin, and placebo respectively. Body temperature and peripheral blood leukocytes were measured at day 1, 2, 7, and 14 after endovascular graft exclusion. Size of AAAs, blood pressure, and blood sugar were measured again after 1 year. RESULTS: In hypertensive patients, the size of AAAs reduced after endovascular graft exclusion, while the combined treatments with cyclopenthiazide, reserpine, or propranolol helped to reduce blood pressure (blood pressure decrease <10 mmHg (18/21), <10 mmHg (12/21), <10 mmHg (8/21), and <10 mmHg (10/21) in the control group, cyclopenthiazide group, reserpine group, and propranolol group, respectively. AAA size decreased in the control group (P<0.001) and in the other three groups (P<0.0001). Similar results were obtained in hyperglycemic patients. The size of AAAs reduced after endovascular graft exclusion. Combined treatment with Metformin and Insulin reduced blood sugar (control, blood sugar >7.8 mmol/L (22/24), AAA size (P<0.001); metformin, blood sugar >7.8 mmol/L (14/24), AAA size (P<0.0001); insulin, blood sugar >7.8 mmol/L (11/24), AAA size (P<0.0001). CONCLUSIONS: Combination of endovascular graft exclusion with medicine is more effective than the former treatment alone for AAA therapy.