In vivo evaluation of safety and performance of a tapered nitinol venous stent with inclined proximal end in an ovine iliac venous model.

A tapered stent with inclined proximal end is designed for fitting the iliac anatomically. The aim of the present study was to evaluate the safety and performance of the new stent in ovine left iliac veins. The experiment was performed in 30 adult sheep, and one nitinol-based VENA-BT® iliac venous stent (KYD stent) was implanted into each animal's left common iliac vein. Follow-up in all sheep consisted of angiographic, macroscopic, and microscopic examinations at Day 0 (< 24 h), Day 30, Day 90, Day 180 and Day 360 post-stenting (six animals per each time-point). 30 healthy ~ 50 kg sheep were included in this study and randomly divided into five groups according to the follow-up timepoint. All stents were implanted successfully into the left ovine common iliac vein. No significant migration occurred at follow-up. There is no statistically significant difference between the groups (p > 0.05), indicating no serious lumen loss occurred during the follow-up period. Common iliac venous pressure was further measured and the results further indicated the lumen patency at follow-up. Histological examinations indicated that no vessel injury and wall rupture, stent damage, and luminal thrombus occurred. There was moderate inflammatory cell infiltration around the stent in Day-0 and Day-30 groups with the average inflammation score of 2.278 and 2.167, respectively. The inflammatory reaction was significantly reduced in Day-90, Day-180 and Day-360 groups and the average inflammation scores were 0.9444 (p < 0.001, Day-90 vs Day-0), 1.167 (p < 0.001, Day-180 vs Day-0) and 0.667 (p < 0.001, Day-90 vs Day-0), respectively. The microscopic examinations found that the stents were well covered by endothelial cells in all follow-up time points. The results suggested that the KYD stent is feasible and safe in animal model. Future clinical studies may be required to further evaluate its safety and efficacy.

Role of microRNA-4739 in enhancing cisplatin chemosensitivity by negative regulation of RHBDD2 in human cervical cancer cells.

BACKGROUND: Cisplatin (DDP) is a widely used chemotherapy drug for advanced cervical cancer (CC), but resistance poses a significant challenge. While miR-4739 has been implicated in tumor development, its specific role in regulating DDP resistance in CC remains unclear. METHODS: We analyzed the expression levels of miR-4739 and RHBDD2 in DDP-resistant and DDP-sensitive CC tissues using quantitative real-time polymerase chain reaction (PCR) and assessed their correlation through Spearman's correlation analysis. DDP-resistant CC cell lines (HeLa/DDP and SiHa/DDP) were established by gradually increasing DDP concentrations, followed by transfection with miR-4739 mimics, si-RHBDD2, or a RHBDD2 overexpression vector. A series of functional assays, including CCK-8 assay, colony formation, flow cytometry, and transwell assay were performed. The interaction between miR-4739 and RHBDD2 was confirmed by luciferase reporter assay. We examined the protein levels of RHBDD2, P-gP, MRP1, cleaved caspase-3, and E-cadherin through western blot analysis. Moreover, we generated xenograft tumors by injecting stably transfected HeLa/DDP cells into mice to compare their tumorigenesis capacity. RESULTS: We observed downregulation of miR-4739 and upregulation of RHBDD2 in DDP-resistant CC tissues and cell lines. MiR-4739 was shown to directly bind to RHBDD2 gene sequences to repress RHBDD2 expression in HeLa/DDP and SiHa/DDP cells. Our in vitro and in vivo experiments demonstrated that overexpressing miR-4739 overcame DDP resistance in CC cells by targeting RHBDD2. Furthermore, RHBDD2 overexpression reversed the effects of miR-4739 mimics on drug-resistance-related proteins (P-gP and MRP1) and the expression of cleaved caspase-3 and E-cadherin in HeLa/DDP cells. CONCLUSIONS: In summary, our study revealed that miR-4739 can reverse DDP resistance by modulating RHBDD2 in CC cells.

Simple and robust 3D bioprinting of full-thickness human skin tissue.

Artificial skins have been used as skin substitutes for wound healing in the clinic, and as in vitro models for safety assessment in cosmetic and pharmaceutical industries. The three-dimensional (3D) bioprinting technique provides a promising strategy in the fabrication of artificial skins. Despite the technological advances, many challenges remain to be conquered, such as the complicated preparation conditions for bio-printed skin and the unavailability of stability and robustness of skin bioprinting. Here, we formulated a novel bio-ink composed of gelatin, sodium alginate and fibrinogen. By optimizing the ratio of components in the bio-ink, the design of the 3D model and the printing conditions, a fibroblasts-containing dermal layer construct was firstly fabricated, on the top of which laminin and keratinocytes were sequentially placed. Through air-liquid interface (ALI) culture by virtue of sterile wire mesh, a full-thickness skin tissue was thus prepared. HE and immunofluorescence staining showed that the bio-printed skin was not only morphologically representative of the human skin, but also expressed the specific markers related to epidermal differentiation and stratum corneum formation. The presented easy and robust preparation of full-thickness skin constructs provides a powerful tool for the establishment of artificial skins, holding critical academic significance and application value.

The Association between Dietary Protein Intake and the Risk of Pancreatic Cancer: Evidence from 14 Publications.

Many studies have been published to assess the association about dietary protein intake on the risk of pancreatic cancer, but with inconsistent result. This meta-analysis aimed to evaluate whether protein intake could affect the risk of pancreatic cancer. A systematic literature search was performed in PubMed, EMBASE and Web of Science up to October 1, 2019. Pooled relative risks (RR) and 95% confidence intervals (CI) were calculated using a random-effect model. A total of 14 studies (12 case-control studies and two cohort studies) were included. Overall, total protein intake had no significant association on the risk of pancreatic cancer (RR = 1.02, 95%CI= 0.85-1.22, I2=45.7%). Subgroup analyses showed such relationships were almost not influenced by study design and geographic location. Interestingly, when we performed the subgroup analysis by protein type, the opposite association was found in animal protein intake (RR = 1.37, 95%CI= 0.93-2.01) and vegetable protein intake (RR = 0.78, 95%CI= 0.54-1.14), although these two groups were not statistically significant. In conclusion, this meta-analysis indicated that dietary total protein intake may be not associated with the risk of pancreatic cancer. However, protein type may be affecting the result which was found from our research. Therefore, studies with detailed information, especially protein type, are warranted to further confirm these findings.

The crescendo pulse frequency of shear stress stimulates the endothelialization of bone marrow mesenchymal stem cells on the luminal surface of decellularized scaffold in the bioreactor.

A completely confluent endothelial cell (EC) monolayer is required to maintain proper vascular function in small diameter tissue-engineered vascular graft (TEVG). However, the most effective method for EC attachment to the luminal surface and formation of an entire endothelium layer that works in vitro remains a complicated challenge that requires urgent resolution. Although pulsatile flow has been shown to be better suited for the generation of functional endothelium, the optimal frequency setting is unknown. Several pulsatile flow frequencies were used to implant rat bone mesenchymal stem cells (MSC) into the lumen of decellularized porcine carotid arteries. The endothelium's integrity and cell activity were investigated in order to determine the best pulse frequency settings. The results showed that MSC were maximally preserved and exhibited maximal morphological changes with improved endothelialization performance in response to increased pulse stimulation frequency. Increased pulse frequency stimulation stimulates the expression of mechanoreceptor markers, cytoskeleton reorganization in the direction of blood flow, denser skeletal proteins fibronectin, and stronger intercellular connections when compared to constant pulse frequency stimulation. MSC eventually develops an intact endothelial layer with anti-thrombotic properties on the inner wall of the decellularized tubular lumen. Conclusion: The decellularized vessels retain the three-dimensional structure of the vasculature, have a surface topography suitable for MSC growth, and have good mechanical properties. By increasing the frequency of pulsed stimulation, MSC endothelialize the lumen of the decellularized vasculature. It is expected to have anti-thrombotic and anti-neointimal hyperplasia properties after implantation, ultimately improving the patency of TEVG.

Overexpression of miR-664 is associated with poor overall survival and accelerates cell proliferation, migration and invasion in hepatocellular carcinoma.

INTRODUCTION: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. This study aimed to investigate the expression patterns of microRNA-664 (miR-664) in HCC tissues and cells, and assess its clinical significance and functional role in HCC. PATIENTS AND METHODS: One hundred and thirty-four paired HCC and non-cancerous tissues were collected from patients who underwent surgery in Qianfoshan Hospital affiliated to Shandong University (Shandong, China) between 2009 and 2012. Expression of miR-664 was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Prognostic value of miR-664 in HCC was evaluated using Kaplan-Meier survival analysis and Cox regression analysis. Cell proliferation was analyzed using the CCK-8 assay, and cell migration and invasion of HCC cells was evaluated by the Transwell assay. RESULTS: Expression of miR-664 was significantly upregulated in HCC tissues and cells when compared with the normal controls (all P<0.05). MiR-664 expression was associated with lymph node metastasis, TNM stage and differentiation (all P<0.05) in the HCC patients. High miR-664 expression predicted poor overall survival (log-rank P=0.004) and acted as an independent prognostic factor (HR =1.945, 95% CI=1.078-3.508, P=0.027). According to cell experiments, the upregulation of miR-664 could promote, whereas the downregulation of miR-664 could inhibit proliferation, migration and invasion of HCC cells (all P<0.05). SIVA1 was predicted as a direct target gene of miR-664 in HCC. CONCLUSION: All data indicated that overexpression of miR-664 is associated with poor prognosis of HCC patients, and may enhance tumor progression of HCC by targeting SIVA1. MiR-664 may be a candidate therapeutic target for HCC treatment.

Diagnosis and treatment of acquired arteriovenous fistula after lower extremity deep vein thrombosis.

BACKGROUND: Deep vein thrombosis (DVT) is a rare cause of arteriovenous fistula (AVF). The pathogenesis of acquired AVF after DVT remains unclear, and publications focusing on therapy and follow-up are also inadequate. In this study, the diagnosis and treatment of 24 patients with acquired AVF in the lower extremity after DVT was reported. METHODS: This is a retrospective study. We studied 24 patients with acquired AVF after DVT who were screened by ultrasound and confirmed by arteriography or computed tomographic arteriography (CTA) in our hospital. Treatments included simple compression therapy (SCT), venous hypertension-relieving therapy (VHRT) and transarterial embolization; VHRT included iliac vein stenting and Palma-Dale surgery (fem-fem bypass). RESULTS: All 24 patients exhibited symptoms in the left lower extremity including swelling (24 cases, 100%), pain (14 cases, 58.33%), pigmentation (13 cases, 54.17%) and ulcers (8 cases, 33.33%). No cardiac enlargement or cardiac insufficiency was reported in any case. The initial ultrasound screening suggested PTS in all 24 cases, with arterialized waveform in veins in 24 cases and high-velocity turbulent flow within the fistulas in 16 cases. The AVF recurrence rate of embolization was 66.7% (4/6). In 7 patients who underwent SCT, the circumference difference of bilateral lower limbs at the 1-year follow-up was not significantly different from that before treatment (thigh, P=0.413; calf, P=0.478). In 14 patients who underwent VHRT, the circumference difference of bilateral lower limbs at the 1-year follow-up was significantly smaller than that before treatment (thigh, P=0.000; calf, P=0.001), and the follow-up difference value of the Venous Insufficiency Epidemiological and Economic Study-Quality of Life (VEINES-QOL) scores was significantly higher than that in the SCT group (1 month, P=0.012; 6 months, P=0.000; 1 year, P=0.000; 2 years, P=0.003). CONCLUSIONS: Ultrasound plays an important role in screening and diagnosing AVF. Iliac vein obstruction rather than AVF was most likely the primary cause of the symptoms. Due to the high recurrence rate of DVT, transarterial embolization of AVF is not effective; thus, VHRT should be recommended as the preferred treatment.

Hybrid Therapy Consisting of Bowel Resection and Fluoroscopic-Assisted Balloon Thrombectomy for Small Bowel Infarction Caused by Acute Mesenteric Venous Thrombosis.

BACKGROUND: To investigate the effect of bowel resection combined with fluoroscopic-assisted balloon thrombectomy for small bowel infarction caused by acute mesenteric venous thrombosis (AMVT). METHODS: Between June 2016 and August 2017, nine patients (seven males and two females; range, 40-73 years; mean, 55.11 ± 10.08 years) with small bowel infarction caused by AMVT underwent bowel resection combined with fluoroscopic-assisted balloon thrombectomy. The demographics, risk factors, therapeutic effect, complications, mortality, and follow-up of the study population were assessed. RESULTS: The effective rate was 100% with substantial clinical improvement in symptoms. All patients underwent small bowel resection with primary anastomosis. The length of bowel resection ranged from 60 to 170 cm (108.67 ± 35.05). In none of the cases there was surgery with second look. The patients were discharged 13-42 days (20.11 ± 8.75) after admission without perioperative complication or death. The follow-up period was 8-21 months (12.89 ± 4.65), and the follow-up rate was 100%. All patients returned to normal activities, regained lost body weight, and remained asymptomatic during the follow-up period. CONCLUSIONS: The combination therapy of bowel resection and fluoroscopic-assisted balloon thrombectomy is technically feasible and may be beneficial for small bowel infarction caused by AMVT in removing a thrombus efficiently, relieving symptoms rapidly, averting second-look surgery, lowering extensive surgical resections, and improving the prognosis.