CircHAT1 regulates the proliferation and phenotype switch of vascular smooth muscle cells in lower extremity arteriosclerosis obliterans through targeting SFRS1.

This study aimed to decipher the mechanism of circular ribonucleic acids (circRNAs) in lower extremity arteriosclerosis obliterans (LEASO). First, bioinformatics analysis was performed for screening significantly down-regulated cardiac specific circRNA-circHAT1 in LEASO. The expression of circHAT1 in LEASO clinical samples was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression of splicing factor arginine/serine-rich 1 (SFRS1), α-smooth muscle actin (α-SMA), Calponin (CNN1), cyclin D1 (CNND1) and smooth muscle myosin heavy chain 11 (SMHC) in vascular smooth muscle cells (VSMCs) was detected by Western blotting. Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) and Transwell assays were used to evaluate cell proliferation and migration, respectively. RNA immunoprecipitation (RNA-IP) and RNA pulldown verified the interaction between SFRS1 and circHAT1. By reanalyzing the dataset GSE77278, circHAT1 related to VSMC phenotype conversion was screened, and circHAT1 was found to be significantly reduced in peripheral blood mononuclear cells (PBMCs) of LEASO patients compared with healthy controls. Knockdown of circHAT1 significantly promoted the proliferation and migration of VSMC cells and decreased the expression levels of contractile markers. However, overexpression of circHAT1 induced the opposite cell phenotype and promoted the transformation of VSMCs from synthetic to contractile. Besides, overexpression of circHAT1 inhibited platelet-derived growth factor-BB (PDGF-BB)-induced phenotype switch of VSMC cells. Mechanistically, SFRS1 is a direct target of circHAT1 to mediate phenotype switch, proliferation and migration of VSMCs. Overall, circHAT1 regulates SFRS1 to inhibit the cell proliferation, migration and phenotype switch of VSMCs, suggesting that it may be a potential therapeutic target for LEASO.

Effect of Shenqi Fuzheng Injection on Leukopenia and T-cell Subsets in Patients with Non-small Cell Lung Cancer Undergoing Radiotherapy.

Purpose: The aim of this study is to evaluate the effect of Shenqi fuzheng injection on leukopenia and T-cell subsets in patients with non-small cell lung cancer (NSCLC) undergoing radiotherapy. Methods: A total of 124 patients with advanced NSCLC treated in the oncology department of our hospital from January 2017 to January 2019 were included and assigned at a ratio of 1 : 1 to receive conventional radiotherapy (control group, n = 62) or conventional radiotherapy plus Shenqi Fuzheng injection (study group, n = 62) via the random number table method. Results: The study group showed a significantly higher objective response rate (ORR) and a lower incidence of leukopenia versus the control group (P < 0.05). After the treatment, Shenqi Fuzheng injection resulted in significantly lower levels of carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) in the study group versus conventional treatment given to the control group. After the treatment, the control group showed significantly decreased ratios of CD3+ T cells, CD4+ T cells, and CD4+/CD8+, and an increased ratio of CD8+ T cells, and significant differences when compared with the study group. The T-cell subsets of the patients in the study group showed no significant changes than those between the treatment. The median OS was 20.0 months in the control group and 23.5 months in the study group. The differences between the two groups in terms of OS did not come up to the statistical standard. Conclusion: Shenqi Fuzheng injection for NSCLC patients undergoing radiotherapy elevates the number of white blood cells, regulates T-cell immune function, reduces tumor markers, and enhances clinical efficacy. Further clinical trials are, however, required prior to clinical promotion.

Long non-coding RNA DLX6-AS1 knockdown suppresses the tumorigenesis and progression of non-small cell lung cancer through microRNA-16-5p/BMI1 axis.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a huge threat to sufferers' life and overall health. Long non-coding RNA (lncRNA) distal-less homeobox 6 antisense RNA 1 (DLX6-AS1) has been revealed to function as a carcinogenesis factor in some cancers. This research aimed to scrutinize the role and mechanism underlying DLX6-AS1 in NSCLC tumorigenesis and progression. METHODS: The levels of DLX6-AS1, microRNA-16-5p (miR-16-5p), and BMI1 mRNA were estimated via reverse transcription-quantitative PCR (RT-qPCR) assay. The protein levels were disclosed by western blot assay. Cell proliferative potential was estimated by colony formation and Cell Counting Kit-8 (CCK-8) assays. Cell migration was estimated by Transwell and wound healing assay. A Transwell assay was executed to estimate cell invasion. The relationships of DLX6-AS1, miR-16-5p, and BMI1 were forecasted by bioinformatics analysis, and confirmed by luciferase reporter assay and RNA immunoprecipitation (RIP) assay. A xenograft mice model was employed to to inspect the function of DLX6-AS1 knockdown on NSCLC tumorigenesis in vivo. RESULTS: DLX6-AS1 was overexpressed in NSCLC tissues and cells, and was inextricably linked with the poor prognosis of NSCLC patients. Depletion of DLX6-AS1 oppressed cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT) but promoted apoptosis in NSCLC. MiR-16-5p is a target of DLX6-AS1 and directly targets BMI1. Moreover, the anti-tumor impacts of miR-16-5p were overturned by overexpression of DLX6-AS1 or BMI1 in NSCLC cells. Additionally, DLX6-AS1 silencing inhibited tumor growth of NSCLC in vivo. CONCLUSIONS: In conclusion, lncRNA DLX6-AS1 downregulation suppressed the tumorigenesis and progression of NSCLC via miR-16-5p/BMI1 axis in vitro and in vivo, elucidating the vital roles and downstream targets of DLX6-AS1 in NSCLC.

Portopulmonary Hypertension: A Complex Case Derived from Multiple Penetrating Trauma-Induced Mesenteric Arteriovenous Fistulae.

Portopulmonary hypertension (PoPH) is a well-recognized complication of portal hypertension. This study reports a case of PoPH that was secondarily caused by post-traumatic mesenteric arteriovenous fistula. A 38-year-old man with a history of knife stabbing wounds in the abdomen in 2003 was admitted to the hospital with exertional shortness of breath and a mechanic murmur over the umbilical region. Computed tomography indicated signs of PoPH and mesenteric arteriovenous fistula. Percutaneous catheter-directed embolization was first performed but failed. Subsequently, the patient was successfully treated with fistula resection and partial enterectomy. The patient had been postoperatively followed regularly, and chief symptoms had been alleviated significantly and pulmonary pressure had successfully decreased to normal range. We believe that this is the first case of PoPH caused by mesenteric arteriovenous fistula.

[Carotid artery stenosis treated with modified carotid endarterectomy: report of two cases].

OBJECTIVE: Based on standard carotid endarterectomy, we performed modified carotid endarterectomy in two cases of carotid artery stenosis by changing the direction of the carotid artery incision to avoid restenosis of the internal carotid artery without using a patch. The two patients recovered smoothly without any complications. Compared with eversion or patch endarterectomy, this modified carotid endarterectomy avoids restenosis of the carotid artery and shortens operation time.

Hairy/enhancer of Split Homologue-1 Suppresses Vascular Endothelial Growth Factor-induced Angiogenesis via Downregulation of Osteopontin Expression.

Angiogenesis plays a critical role in the progression and vulnerability of atherosclerotic plaques; however, the orchestration of angiogenesis in atherosclerotic plaque formation remains unclear. The results of microarray analysis, real-time PCR and immunohistochemical analyses showed that Hairy/enhancer of split homologue-1 (Hes-1) expression was significantly decreased, while that of osteopontin (OPN) was increased, in atherosclerotic plaques. Meanwhile, immunofluorescence results demonstrated that both Hes-1 and OPN were expressed in endothelial cells (ECs) of neovessels in atherosclerotic plaques. The results of an in vitro study showed that Hes-1 was downregulated, while OPN was upregulated, in a time- and dose-dependent manner in human umbilical vein endothelial cells (HUVECs) by VEGF treatment. In addition, Hes-1 knockdown was found to have transcriptional promotion effect on OPN expression in HUVECs and enhance OPN-induced angiogenesis in response to VEGF. On the contrary, Hes-1 overexpression inhibited OPN expression in HUVECs and reduced angiogenesis in vitro and in vivo. The results of this study suggest that decreased Hes-1 expression in atherosclerotic plaques exaggerate VEGF-induced angiogenesis by upregulating OPN. Therefore, restoring Hes-1 expression and inhibiting OPN expression may be a promising strategy to prevent vulnerable plaque formation in patients with atherosclerosis.

Impact of genetic polymorphisms in thrombin activatable fibrinolysis inhibitor (TAFI) on venous thrombosis disease: A meta-analysis.

BACKGROUND: Reported studies have showed that Thrombin Activatable Fibrinolysis Inhibitor (TAFI) may be associated with an increased risk of venous thromboembolism. But the relation of VT with TAFI gene SNPs could not be clearly demonstrated. Thus, we conducted a meta-analysis to analyze the associations between three TAFI variants -438G/A, 505G/A and 1040C/T and the risk of venous thrombosis. METHODS: We carried out a systematic search to obtain all the eligible studies published before 30th October 2014. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were computed to assess the association. RESULTS: 13 eligible studies were enrolled including 2321 patients and 2464 controls. There was a significant association between 505G/A and the risk of VTD under all models except recessive model (G vs. A: OR=1.13, 95% CI: 1.02, 1.26; GG vs. AA:OR=1.47, 95% CI: 1.14, 1.88; GA vs. AA: OR=1.36, 95% CI: 1.06, 1.73; GG+GA vs. AA: OR=1.41, 95% CI: 1.12, 1.77). Similarly, obvious relationship was observed in subgroup analyses in light of type of disease and ethnicity. Likewise, for 1040C/T variant, significant associations were identified under homozygote, heterozygote and dominant models (CC vs. TT: OR=1.65, 95% CI: 1.06, 2.59; CT vs. TT: OR=1.55, 95% CI: 1.19, 2.03; CC+CT vs. TT: OR=1.55, 95% CI: 1.20, 2.00). Sub-analysis presented significant associations in non-CVT and non-Asian group under homozygote, heterozygote, and dominant models and CVT group in recessive model. CONCLUSION: This meta-analysis showed that -438G/A variant was not associated with the incidence of venous thrombosis. But in non-Asian populations, G allele and GG genotype of 505G/A may increase the risk of venous thrombosis diseases. GG genotype of 505G/A and one C carrier (CC and CT) of 1040C/T gave rise to the development of venous thrombosis diseases except CVT. Additionally, the heterozygote CT may be a potential contributing factor of gene effect in venous thrombosis.

[Hybrid operation for acute left leg deep venous thrombosis secondary to left iliac vein compression syndrome: analysis of 36 cases].

OBJECTIVE: To evaluate the surgical techniques for acute left deep venous thrombosis (LDVT) secondary to left iliac vein compression syndrome (IVCS). METHODS: Thirty-six patients with acute LDVT secondary to IVCS received inferior vena cava filter placement, and in 2 of the cases, stent implantation was canceled for acute episode of obsolete DVT. The remaining 34 patients underwent left femoral venotomy for iliofemoral thrombectomy with Fogarty catheter and distal femoral vein thrombus removal by sequential compression of the legs, followed by implantation of stent-graft (2 cases) or bare-metal stents (32 cases) in the left common iliac veins. With routine anticoagulation and thrombolytic treatments, the patients were regularly examined for postoperative blood flow in the affected limb. RESULTS: In 2 of the cases undergoing bare-metal stent implantation, the residue thrombi were squeezed into the stent by balloon, which was managed subsequently with local thrombolysis. One patient with bare-metal stent implantation received a secondary stenting for posterior stent displacement. Three patients had self-limited bleeding due to decreased serum FBG. Significant improvements were achieved at 3, 6, 30 and 180 days postoperatively in the circumferences of the affected limb (P<0.05) and in the levels of D-dimer (P=0.011), and FBG level showed no significant variations (F=1.163, P=0.345). The total rate of excellent outcomes was 83.3% (26/34) with a total effective rate of 91.2% (31/34) in these cases. CONCLUSIONS: Thrombectomy to revascularize the inflow tract and stent implantation to enlarge stenosed iliac veins are key issues in treatment of acute LDVT secondary to IVCS.

[Hybrid operation for acute left leg deep venous thrombosis secondary to left iliac vein compression syndrome: analysis of 36 cases].

OBJECTIVE: To evaluate the surgical techniques for acute left deep venous thrombosis (LDVT) secondary to left iliac vein compression syndrome (IVCS). METHODS: Thirty-six patients with acute LDVT secondary to IVCS received inferior vena cava filter placement, and in 2 of the cases, stent implantation was canceled for acute episode of obsolete DVT. The remaining 34 patients underwent left femoral venotomy for iliofemoral thrombectomy with Fogarty catheter and distal femoral vein thrombus removal by sequential compression of the legs, followed by implantation of stent-graft (2 cases) or bare-metal stents (32 cases) in the left common iliac veins. With routine anticoagulation and thrombolytic treatments, the patients were regularly examined for postoperative blood flow in the affected limb. RESULTS: In 2 of the cases undergoing bare-metal stent implantation, the residue thrombi were squeezed into the stent by balloon, which was managed subsequently with local thrombolysis. One patient with bare-metal stent implantation received a secondary stenting for posterior stent displacement. Three patients had self-limited bleeding due to decreased serum FBG. Significant improvements were achieved at 3, 6, 30 and 180 days postoperatively in the circumferences of the affected limb (P<0.05) and in the levels of D-dimer (P=0.011), and FBG level showed no significant variations (F=1.163, P=0.345). The total rate of excellent outcomes was 83.3% (26/34) with a total effective rate of 91.2% (31/34) in these cases. CONCLUSIONS: Thrombectomy to revascularize the inflow tract and stent implantation to enlarge stenosed iliac veins are key issues in treatment of acute LDVT secondary to IVCS.

[Efficacy of regional administration of urokinase and argatroban via small saphenous vein catheter for treatment of acute deep venous thrombosis in the lower limb].

OBJECTIVE: To investigate the clinical value of local regional administration of urokinase and argatroban through small saphenous vein (SSV) catheter in the treatment of acute deep venous thrombosis in the lower limb (LDVT). METHODS: Fifty-six patients with acute LDVT were prospectively randomized into the study group (21 cases, 24 limbs) and control group (35 cases, 36 limbs) for treatment with urokinase and argatroban regionally administered via the SSV catheter and with the same agents given via the peripheral vein, respectively. The patients were examined for changes in serum fibrinogen (FBG) and D-dimer and the perimeter of the affected limbs, and the complications in relation to the agents were observed. RESULTS: By corrected Chi-square test, the incidence of complications was significantly lower in the study group than in the control group (1/21 vs 4/36, χ(2)=1.92, P≤0.05). Wilcoxon's sign rank test suggested no statistically significant difference between the two groups in the total effective rate (95.8% vs 94.4%, V=0.52, P>0.05), but the total excellent rate differed significantly between them (83.3% vs 55.6%, V=2.36, P≤0.05). Serum FBG underwent no significant variations in the study group during thrombolysis (P>0.05), but decreased significantly in the control group (P≤0.05). The decreases in serum D-dimer and perimeter of the affected limbs occurred earlier in the study group than in the control group (P≤0.05). CONCLUSION: Regional administration of urokinase and argatroban via small saphenous vein catheter can promote the thrombolytic effect and reduce the risk of hemorrhage in the treatment of LDVT.

[Experience with endovenous laser treatment combined with high ligation and Muller's phlebectomy for C3-6 grade primary superficial varicose in the lower limbs].

OBJECTIVE: To summarize the experience with endovenous laser treatment(EVLT) combined with high ligation and Muller's phlebectomy for primary superficial varicose in the lower limbs. METHODS: In 95 patients with C3-6 grade primary superficial varicose in 146 lower limbs, the extent of varicose was accurately marked, the guiding wires were manipulated precisely, and the proximal great saphenous veins (GSV) were ligated after exsanguinations. The stems of the GSV were ablated with laser with the lower limbs lift up and pressed hard along the stems, and Muller's incisions were carefully planned. RESULTS: All the operations were completed successfully. The guiding wires entered into the deep veins through the communicating branches in 2 limbs, 1 patient experienced capillary hemorrhage from Muller's incisions, 8 had thrombotic phlebitis of the GSV, 7 sustained heat-related injury of the saphenous nerves, 1 experienced skin heat-related lesion, 2 developed hematoma in the inguinal region, 2 had pitting edema in the dorsum of the foot, 1 had fat liquefaction of the Muller incision, and 1 showed rejection of the thrum. After conservative treatment, all the patients recovered and were discharged. Part of the superficial varicose remained after the operation in 6 limbs. CONCLUSION: It is necessary to standardize the routine procedure of EVLT combined with high ligation and Muller's phlebectomy to reduce the complications.