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G protein-coupled receptor 39 (GPR39) agonist weakens oxidized low-density lipoprotein (ox-LDL)-induced attachment of monocytes to vascular endothelial cells and thus alleviates atherosclerosis. This study looks at whether GPR39 protects macrophages against ox-LDL-induced inflammation and apoptosis and ameliorates lipid accumulation in atherosclerosis and investigates its mechanism. Following inducement of ox-LDL, the expression of GPR39 and tumor necrosis factor alpha-induced protein 3 (TNFAIP3, also known as A20) in Raw 264.7 cells was detected by RT-qPCR and western blotting. The viability of macrophages treated with GPR39 agonist was detected by a cell counting kit 8 kit. GPR39 and A20 expression in ox-LDL-challenged macrophages was assayed by RT-qPCR and western blot with or without GPR30 agonist. After transfection of small interfering RNA (siRNA)-A20, the expression of pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 and anti-inflammatory cytokine IL-10 as well as NF-κB p65 and COX2 was detected. Lipid accumulation was observed through Oil Red O Staining. Total cholesterol (TC) and free cholesterol (FC) in macrophages were detected by commercial kits. Lastly, macrophage apoptosis was observed through TUNEL, and apoptosis-related proteins were detected by western blotting . Results indicated that decreased expression of GPR39 and A20 was observed in ox-LDL-induced macrophages. GPR39 agonist significantly increased A20 expression in ox-LDL-treated macrophages. Furthermore, A20 interference reversed the inhibitory effect of GPR39 agonist on ox-LDL-induced inflammation, lipid accumulation, TC and FC overexpression as well as cell apoptosis. In conclusion, activating GPR39 alleviates ox-LDL-induced macrophage inflammation, lipid accumulation and apoptosis in an A20-dependent manner., Graphical abstract

To determine the efficacy of Venastent - a novel iliac vein stent for non-thrombotic iliac vein lesions (NIVLs).From October 2018 to January 2021, 256 NIVL patients were recruited at 19 Chinese hospitals. A randomised controlled trial was conducted to compare the efficacy of the new iliac vein stent-Venastent (Tianhong China) with Zilver stent (Cook USA). All patients were allocated randomly to two groups: the experimental group patients used Venastent, while the control group received the Zilver stent. The trial was registered in Chinese Clinical Trial Registry (ChiCTR2200057851).A total of 123 patients in the experimental group and 122 patients in the control group had a full set of data collected (p = ns). The technical success rate was 100% (n = 245/245). The patency rate was 100% (n = 123/123) in the experimental group and 98.4% (n = 120/122) in control group one year after operation (p = ns). The lower extremity swelling remission rate was 79.1% (n = 87/110) in the experimental group and 78.4% (n = 91/116) in the control group (p = ns). The lower extremity pain relief rate was 68.8% (n = 50/80) in the experimental group and 77.2% (n = 71/92) in the control group (p = ns). The ulcer healing rate was 90% (n = 18/20) in the experimental group and 87% (n = 20/23) in the control group (p = ns). There was no difference in stent re-stenosis or clinical remission between the two groups.The new iliac vein stent, Venastent, had a comparable high patency rate and safety profile as the Zilver stent (Cook) in NIVLs patients. Venastent significantly reduced symptoms of chronic venous disease.

Vascular smooth muscle cell (VSMC) proliferation and migration play critical roles in the development and progression of atherosclerosis. C1q/tumor necrosis factor-related protein 6 (CTRP6), a member of CTRPs family, was involved in cardiovascular diseases, inflammatory reaction and adipogenesis. However, the role of CTRP6 in VSMCs remains largely unknown. The purpose of this study is to investigate the effects of CTRP6 on VSMC proliferation and migration and explore the possible mechanism. Our results indicated that CTRP6 expression was dramatically down-regulated in human atherosclerotic tissues and in cultured VSMCs stimulated by platelet-derived growth factor-BB (PDGF-BB). In addition, CTRP6 overexpression significantly inhibited the proliferation and migration of VSMCs exposed to PDGF-BB, as well as increased expression of α-SMA and SM22α in PDGF-BB-stimulated VSMCs. Furthermore, CTRP6 overexpression efficiently prevented the activation of PI3K/Akt/mTOR in VSMCs in response to PDGF-BB. In conclusion, these findings showed that CTRP6 inhibits PDGF-BB-induced VSMC proliferation and migration, at least in part, through suppressing the PI3K/Akt/mTOR signaling pathway. Therefore, CTRP6 may be a potential target for the treatment of atherosclerosis.

Tissue factor pathway inhibitor 2 (TFPI-2), also known as placental protein and matrix-associated serine protease inhibitor, plays an important role in angiogenesis, intravascular fibrinolysis, wound healing, tumor invasion, metastasis by plasmin, and trypsin mediated activation of zymogen matrix metalloproteinases. To detect whether TFPI-2 can be expressed in human pancreatic carcinoma samples and to investigate its role in the growth, invasion, and metastasis of pancreatic carcinoma cell in vitro and in vivo, we collected eight normal pancreatic tissue samples and 50 pancreatic carcinoma samples, and stably transfected the human pancreatic carcinoma cell line Panc-1 with a vector capable of expressing TFPI-2 gene. RT-PCR and Western blot analysis revealed that the levels of TFPI-2 expression were markedly lower in pancreatic carcinoma samples compared with normal pancreas samples. The level of TFPI-2 protein was significantly higher in cells transfected with TFPI-2 gene than that in the untransfected cells. The results of MTT assay showed that TFPI-2 inhibited Panc-1 cells growth in vitro. The invasive capacity of the cells transfected with TFPI-2 gene was also markedly less than that of untransfected cells in vitro as determined by the Matrigel invasion/migration assay. Moreover, TFPI-2 inhibited tumor growth, invasion, and metastasis in vivo in an orthotopic pancreatic carcinoma model. Our findings suggest that TFPI-2 plays a significant role in the growth, invasion, and metastasis of pancreatic carcinoma cell in vitro and in vivo, and has potential in anticancer therapy.

Tissue factor pathway inhibitor-2 (TFPI-2) is a matrix-associated kunitz-type serine proteinase inhibitor that plays an important role in plasmin and trypsin-mediated activation of zymogen matrix metalloproteinases involved in tumor angiogenesis, invasion and metastasis. Earlier studies have shown that the production of TFPI-2 is downregulated during the progression of various tumors. To detect whether TFPI-2 can be expressed in human pancreatic carcinoma samples, to evaluate its prognostic significance on pancreatic carcinoma and to investigate its effect on tumor invasion and metastasis, we collected 9 normal pancreatic tissue samples and 41 pancreatic carcinoma samples and stably transfected the human pancreatic carcinoma cell line Panc-1 with a vector capable of expressing TFPI-2 gene. RT-PCR and Western blot analysis revealed that the expression of TFPI-2 in pancreatic carcinoma samples was markedly lower than that in normal pancreas samples, and there was no TFPI-2 expression in Panc-1 cell. Its expression was related with biological characters of pancreatic carcinoma. The results of Boyden chamber assay and orthotopic pancreatic carcinoma model showed that TFPI-2 could inhibit invasion and metastasis ability of pancreatic carcinoma in vitro and in vivo. Kaplan-Meier survival curve and Cox proportional hazards model assay identified TFPI-2 as an independent prognostic factor for pancreatic carcinoma. Our data suggest that TFPI-2 plays a significant role in the invasion and metastasis of pancreatic carcinoma cell in vitro and in vivo and is determined to be an important prognostic factor for pancreatic carcinoma patients.

Partial portosystemic shunts have been popularized because of a reported low rate of mortality and morbidity (especially encephalopathy, liver failure and occlusion). The results of partial portacaval shunts [small-diameter expanded polytetrafluoroethylene (ePTFE) H-graft portacaval shunt] were retrospectively reviewed to evaluate the clinical efficacy in the treatment of portal hypertension. Forty-three patients with portal hypertension were treated by small-diameter H-graft of ePTFE portacaval shunt from May 1995 to April 2006. Thirty-three had externally ringed grafts and ten had non-ringed ones. Ten had grafts of 10 mm in diameter and 33 had grafts of 8 mm. The left gastric artery and coronary vein were ligated in all the cases. Six had pericardial devascularization and splenectomy was performed in 42. An average decrease of free portal pressure (FPP) from (33.24 ± 4.78) cmH2O before shunting and (13.65 ± 5.65) cmH2O after shunting was observed. The portal blood flow was reduced by one-third of that before shunt. Thirty-eight patients survived and no upper gastro-intestinal rebleeding occurred in the follow-up period (50.5 months in average). Two were out of contact. Color Doppler ultrasonography and/or portography revealed the shunts were patent in 38 cases and were occluded in three cases (3/41, 7.3%). Encephalopathy developed in five cases (5/41, 12.2%). Partial (small-diameter ePTFE H-graft) portacaval shunting can reduce the portal pressure effectively. Majority of the hepatic flow from the portal vein can be maintained adequately. The shunts with reinforced grafts can keep a higher rate of patency. The morbidity of encephalopathy was lower than those with total shunt. The partial portacaval shunt is effective in preventing recurrent variceal bleeding.