Treatment of patent ductus arteriosus and short-term outcomes among extremely preterm infants: a multicentre cohort study.

Background: The optimal treatment strategy for patent ductus arteriosus (PDA) in extremely preterm infants is currently highly controversial. This study aimed to evaluate the association between PDA treatment and short-term outcomes among extremely preterm infants. Methods: This cohort study included all extremely preterm infants (≤27 and 6/7 weeks) who were admitted to hospitals participating in the Chinese Neonatal Network from January 2019 to December 2021, and were diagnosed to have PDA by echocardiogram. PDA treatment was defined as medical treatment and/or surgical ligation of PDA during hospitalization. Short-term outcomes included death, bronchopulmonary dysplasia (BPD), death/BPD, retinopathy of prematurity, necrotizing enterocolitis, and severe brain injury. Multivariate logistic regression was used to evaluate the association between PDA treatment and outcomes. Subgroup analysis were performed among infants with different respiratory support on 3 and 7 days of life. Findings: A total of 2494 extremely preterm infants with the diagnosis of PDA were enrolled, of which 1299 (52.1%) received PDA treatment. PDA treatment was significantly associated with lower risk of death (adjusted odds ratio, 0.48; 95% confidence interval, 0.38-0.60). The decreased risk of death was accompanied by increased risk of BPD and death/BPD. In subgroup analysis according to respiratory support, PDA treatment was associated with lower risk of death among infants who required invasive ventilation. However, the beneficial effect on death was not significant among infants who did not require invasive ventilation. Interpretation: PDA treatment was associated with reduced mortality in extremely preterm infants, but this beneficial effect was mainly present among infants who required invasive ventilation. Funding: This study was funded by the Shanghai Science and Technology Commission's Scientific and Technological Innovation Action Plan (21Y21900800) and the Canadian Institutes of Health Research (CTP87518).

The controlling nutritional status score predicts postoperative mortality in patients with ruptured abdominal aortic aneurysm: a retrospective study.

Background: Ruptured abdominal aortic aneurysms (rAAAs) are challenging for vascular surgeons because they have a high mortality rate. In many diseases, nutritional status is closely associated with prognosis. The Controlling Nutritional Status (CONUT) screening tool score is a prognostic factor in some malignant and chronic diseases; however, the impact of nutritional status on rAAA has not yet been reported. In this study, we explored the relationship between the CONUT score and the postoperative prognosis of patients with rAAA. Methods: This was a retrospective review of 39 patients with rAAA who underwent surgical treatment from March 2018 to September 2021 at one center. Patient characteristics, nutritional status (CONUT score), and postoperative status were recorded. The patients were divided into groups A and B based on the CONUT score. The baseline characteristics of the two groups were compared, and Cox proportional hazards and logistic regression analyses were used to determine independent predictors of mid-term mortality and complications, respectively. Results: The overall mid-term mortality rate was 28.21% (11/39). Compared with group A, group B had higher intraoperative (P = 0.047) and mid-term mortality (P = 0.033) rates. The univariate analysis showed that age [hazard ratio (HR), 1.098; 95% confidence interval (CI), 1.019-1.182; P = 0.014], CONUT score (HR, 1.316; 95% CI, 1.027-1.686; P = 0.03), and surgical procedure (HR, 0.127; 95% CI, 0.016-0.992; P = 0.049) were associated with mid-term mortality, whereas the multivariate analysis showed that the CONUT score (HR, 1.313; 95% CI, 1.009-1.710; P = 0.043) was an independent predictor of mid-term mortality. The multivariate logistic regression analysis did not reveal any associations with complications. The Kaplan-Meier curves showed that group B had a lower mid-term survival rate (log-rank P = 0.024). Conclusion: Malnutrition is closely associated with the prognosis of patients with rAAA, and the CONUT score can be used to predict mid-term mortality.

[Early risk factors for death in neonates with persistent pulmonary hypertension of the newborn treated with inhaled nitric oxide]. / ç»ä¸€æ°§åŒ–æ°®å¸å ¥æ²»ç–—çš„æ–°ç”Ÿå„¿æŒç»­è‚ºåŠ¨è„‰é«˜åŽ‹æ‚£å„¿æ­»äº¡çš„æ—©æœŸå½±å“å› ç´ åˆ†æž.

OBJECTIVES: To evaluate the early risk factors for death in neonates with persistent pulmonary hypertension of the newborn (PPHN) treated with inhaled nitric oxide (iNO). METHODS: A retrospective analysis was performed on 105 infants with PPHN (gestational age ≥34 weeks and age <7 days on admission) who received iNO treatment in the Department of Neonatology, Children's Hospital of Nanjing Medical University, from July 2017 to March 2021. Related general information and clinical data were collected. According to the clinical outcome at discharge, the infants were divided into a survival group with 79 infants and a death group with 26 infants. Univariate and multivariate Cox regression analyses were used to evaluate the risk factors for death in infants with PPHN treated with iNO. The receiver operating characteristic (ROC) curve was used to calculate the cut-off values of the factors in predicting the death risk. RESULTS: A total of 105 infants with PPHN treated with iNO were included, among whom 26 died (26/105, 24.8%). The multivariate Cox regression analysis showed that no early response to iNO (HR=8.500, 95%CI: 3.024-23.887, P<0.001), 1-minute Apgar score ≤3 points (HR=10.094, 95%CI: 2.577-39.534, P=0.001), a low value of minimum PaO2/FiO2 within 12 hours after admission (HR=0.067, 95%CI: 0.009-0.481, P=0.007), and a low value of minimum pH within 12 hours after admission (HR=0.049, 95%CI: 0.004-0.545, P=0.014) were independent risk factors for death. The ROC curve analysis showed that the lowest PaO2/FiO2 value within 12 hours after admission had an area under the ROC curve of 0.783 in predicting death risk, with a sensitivity of 84.6% and a specificity of 73.4% at the cut-off value of 50, and the lowest pH value within 12 hours after admission had an area under the ROC curve of 0.746, with a sensitivity of 76.9% and a specificity of 65.8% at the cut-off value of 7.2. CONCLUSIONS: Infants with PPHN requiring iNO treatment tend to have a high mortality rate. No early response to iNO, 1-minute Apgar score ≤3 points, the lowest PaO2/FiO2 value <50 within 12 hours after admission, and the lowest pH value <7.2 within 12 hours after admission are the early risk factors for death in such infants. Monitoring and evaluation of the above indicators will help to identify high-risk infants in the early stage.

Nonocclusive mesenteric ischemia caused by type B aortic dissection: a case report.

BACKGROUND: Nonocclusive mesenteric ischemia (NOMI) is defined as acute intestinal ischemia because of decreased blood flow in mesenteric vessels. Only a few cases of NOMI that occur secondary to aortic dissection (AD) have been reported, resulting in the lack of sufficient knowledge of diagnosis and treatment. CASE PRESENTATION: We aimed to report a case of NOMI caused by type B Aortic Dissection. A 26-year-old male patient was transferred to our hospital with the diagnose of NOMI and aortic dissection in April 2018. The abdominal computed tomography (CT) assists the diagnosis of paralytic intestinal obstruction, intestinal wall pneumatosis, and perforation. Emergency laparotomy revealed that the bowel wall supplied by the superior mesenteric artery (SMA) was pale with the palpable but weak pulsation of the parietal artery. The small intestine was extremely dilated with a paper-thin, fragile wall that was ruptured easily and could not be sutured. In this case, extensive resection and segmental drainage were done. Postoperatively, the digestive tract was reconstructed. However, the patient suffered from iron deficiency anemia and short bowel syndrome eight months later, and unfortunately died from long-term complications. CONCLUSION: Aortic dissection leads to continuous decrease in blood pressure and blood flow to the SMA, considering as a predisposing factor for NOMI. During the treatment, extensive resection and segmental drainage are the optimal surgical strategy, which can make benefit in emergencies especially.

Elizabethkingia anophelis: An Important Emerging Cause of Neonatal Sepsis and Meningitis in China.

Elizabethkingia anophelis, originally isolated from the midgut of Anopheles gambiae in 2011, is an important cause of sepsis in adults and children and meningitis in newborns, with several reported outbreaks worldwide. Accumulating molecular biological and whole-genome sequencing (WGS) evidence suggests that E. anophelis is the major human pathogen belonging to the genus Elizabethkingia. The source of infection, routes of transmission and pathogenicity of E. anophelis are unclear and should be better understood as the bacterium is capable of causing sepsis and meningitis in newborns, with complications and high mortality rates. Here, we describe two healthy neonates who developed meningitis caused by Elizabethkingia infection. Initial conventional laboratory results revealed that the pathogen was E. meningoseptica; metagenomic findings later confirmed it as E. anophelis. We also summarize reported E. anophelis infections among newborns in China and elsewhere and describe the clinical, pathogenic and genetic characteristics of this bacillus.

TGF-ß Signaling Induces the Expression of OPN in Blood Vessel Endothelial Cells.

BACKGROUND: The mechanism of blood vessel formation and degeneration still remains unclear. Transforming growth factor-ß1 (TGF-ß1) signaling is a critical pathway in this progression and can induce multiple biological effects. Osteopontin (OPN) is involved in mineral metabolism and the inflammatory response associated with vascular calcification. METHODS: To identify the relationship between TGF-ß signaling pathway and OPN, we stimulated human vascular endothelial cells (HVECs) and human aortic endothelial cells (HAECs) using various concentration of TGF-ß1 in vitro. RESULTS: As assessed by flow cytometry and western blots, apoptosis levels were significantly increased with TGF-ß1 treatment. We also demonstrated that OPN increased in vitro with TGF-ß signaling by western blot and quantitative real time polymerase chain reaction (qRT-PCR) analyses. The inhibitory phosphorylation of endothelial nitric-oxide synthase (eNOS) (Thr495) was also up-regulated by TGF-ß signaling. Meanwhile, the anti-inflammatory factor Nrf2 and the activating phosphorylation of eNOS (Ser1177) were down-regulated. CONCLUSIONS: Taken together, our findings demonstrate that TGF-ß signaling can induce the expression of OPN, which may play an important role in the dysfunction of the vascular wall.

Long-Term Outcome of Catheter-Directed Thrombolysis in Pregnancy-Related Venous Thrombosis.

BACKGROUND Venous thromboembolism (VT) is a leading cause of maternal mortality and morbidity worldwide. Catheter-directed thrombolysis (CDT) is an effective and safe treatment modality for VT patients. However, the long-term outcome of CDT in pregnancy-related venous thrombosis are unclear. The aim of this study was to assess long-term results of pregnancy-related VT patients. MATERIAL AND METHODS We reviewed 41 pregnancy-related deep venous thrombosis (DVT) patients who underwent CDT from February 2008 to May 2015. Clinical data, including demographic variables, disease location, vascular risk factors, treatment regimen, interventional procedure and complications, were collected retrospectively. Clinical and color-duplex ultrasonography were performed to monitor venous patency during follow-up. Post-thrombotic syndrome (PTS) was assessed with the Villalta scale and quality of life (QOL) was evaluated by the VEINES-QOL/Sym questionnaire. RESULTS Twenty-three patients underwent spontaneous abortion or induced abortion within 3 months before DVT, and 18 patients had DVT during the first 3 months after delivery. Technical success was achieved in all patients. Grade III (complete) lysis was obtained in 15 patients and grade II (partial) lysis was obtained in 21 patients. The follow-up period was 3 years. Twenty-eight patients had venous patency at 3-year follow-up; 36.6% of patients developed mild or moderate PTS (Villalta score 5-14) and 4.8% with severe PTS (Villalta score ≥15). VEINES-QOL/Sym scores were 55.24±7.35 and 53.25±6.65, respectively. CONCLUSIONS Catheter-directed thrombolysis is a reliable and safe treatment modality for postnatal or abortion patients with DVT. CDT can reduce the incidence rate of PTS and increase the quality of life.

Resveratrol Improves Endothelial Progenitor Cell Function through miR-138 by Targeting Focal Adhesion Kinase (FAK) and Promotes Thrombus Resolution In Vivo.

BACKGROUND Endothelial progenitor cells (EPCs) were found to be a potential therapeutic choice for low extremity deep vein thrombosis. The aim of our research was to investigate the effect of resveratrol (RSV) on EPCs that may promote thrombus resolution and its potential pathway. MATERIAL AND METHODS EPCs were pretreated with RSV and migration; angiogenesis were evaluated ex vivo. Expression of miR-138 and focal adhesion kinase (FAK) was also tested. A murine model of venous thrombosis was developed as an in vivo model. The effects of RSV treatment on mice with inferior venous thrombosis were evaluated. RESULTS We found that RSV increased EPCs migration and tube formation ex vivo. RSV significantly inhibited miR-138 expression. Moreover, we demonstrated that FAK was a target of miR-138 and revealed that FAK knockdown downregulated migration and angiogenesis of RSV-treated EPCs. In addition, RSV-induced EPCs promoted thrombus resolution in a murine model of venous thrombosis. CONCLUSIONS We found the first evidence that intravenous injection of RSV-treated EPCs enhanced thrombus resolution in vivo. RSV exerted its role by reducing miR-138 expression and therefore upregulated FAK.

Bidirectional Pull-Back Technique for Retrieval of Strut-Embedded Cylinder-Shaped Filters in Inferior Vena Cava.

BACKGROUND IVC filters have been widely accepted as an effective method to prevent pulmonary embolism (PE) in patients with deep venous thrombosis (DVT). However, the placement of IVC filters is associated with significant complications and filter retrieval can be challenging when the filter struts are embedded into the caval wall. MATERIAL AND METHODS Over 26 months, we reviewed the safety and efficacy of the bidirectional pull-back technique for removing strut-embedded IVC filters in 15 consecutive patients. Retrieval procedural data such as in-dwell time, retrieval time, and fluoroscopy time were recorded. Clinical outcomes and procedure-related complications were evaluated by venography or enhanced computed tomography. Histologic tissue was analyzed to reveal the pathologic effects of chronic filter implantation. All patients underwent routine clinical follow-up at a mean time of 12 months (range, 8-14 months). RESULTS Technical success of filter retrieval was achieved in 100%, with mean implantation of 46.6 days (range, 27-66 days). Filter types were as follows: OptEase (n=11) and Aegisy (n=4). The mean retrieval time and fluoroscopy time were 21.43±5.42 min and 7.63±2.67 min, respectively. Immediate postprocedure venography showed no procedure-related complications. Thirteen patients discontinued previously prescribed lifelong anticoagulation. There were no long-term complications during follow-up. CONCLUSIONS The bidirectional pull-back technique is safe and efficient for filter retrieval. This complex technique can be particularly useful in selected patients to remove strut-embedded cylindrical-shaped IVC filters previously considered irretrievable.

Metformin inhibits endothelial progenitor cell migration by decreasing matrix metalloproteinases, MMP-2 and MMP-9, via the AMPK/mTOR/autophagy pathway.

The aim of the present study was to investigate the effect of metformin on endothelial progenitor cell (EPC) migration and to explore the possible mechanisms. EPCs were treated with metformin, and the migration of EPCs was evaluated by wound healing and Matrigel invasion assays. We also examined the expression levels of of MMP-2 and MMP-9 in EPCs with or without metformin treatment via RT-PCR and western blot analysis, and activities of MMP-2 and MMP-9 in EPCs under different conditions was examined by zymography. Moreover, we also assessed the AMPK/mTOR/autophagy pathway to explore the possible mechanisms. Metformin treatment significantly downregulated matrix metalloproteinase-2 (MMP-2) and MMP-9 expression, and subsequently decreased the migration of EPCs. Increased levels of phosphorylated (p)-AMPK and LC3II expression, as well as decreased levels of p-mTOR and p62 contributed to this phenomenon. The AMPK inhibitor compound C reversed the effect exerted by metformin. In conclusion, our results showed that metformin inhibited the migration of EPCs by decreasing MMP-2 and MMP-9. The AMPK/mTOR/autophagy pathway was demonstrated to be involved in the regulatory mechanisms.

Mid-term outcome of endovascular treatment for acute lower extremity deep venous thrombosis.

Purposes of the study To evaluate the benefit of stenting the iliac vein in patients with residual iliac vein stenosis treated with catheter-directed thrombolysis for acute iliofemoral deep venous thrombosis. Procedures In this randomized prospective study, patients with a first-time acute lower extremity deep venous thrombosis that had persisted <14 days were treated with catheter-directed thrombolysis. After catheter-directed thrombolysis, patients with >50% residual iliac vein stenosis were randomly divided into two groups: catheter-directed thrombolysis + Stent Group and catheter-directed thrombolysis Alone Group. Patients received urokinase thrombolysis and low-molecular-weight heparin/oral warfarin during the hospitalization period and were administrated oral warfarin after discharge. Cumulative deep vein patency, the Clinical Etiology Anatomic Pathophysiologic classification system, the Venous Clinical Severity Score and the Chronic Venous Insufficiency Questionnaire score were evaluated. Findings The cumulative deep vein patency rate was 74.07% in the catheter-directed thrombolysis + Stent Group and 46.59% in the catheter-directed thrombolysis Alone Group. The mean postoperative Clinical Etiology Anatomic Pathophysiologic classification and Venous Clinical Severity Score was significantly lower in the catheter-directed thrombolysis + Stent Group than in the catheter-directed thrombolysis Alone Group. The mean postoperative Chronic Venous Insufficiency Questionnaire score was significantly higher in the catheter-directed thrombolysis + Stent Group than the catheter-directed thrombolysis Alone Group. Conclusions Placement of an iliac vein stent in patients with residual iliac vein stenosis after catheter-directed thrombolysis for acute lower extremity deep venous thrombosis increases iliac vein patency and improves clinical symptoms and health-related quality of life at mid-term follow-up compared to patients treated with catheter-directed thrombolysis alone.

Risk factors for and causes and treatment of recurrence of inferior vena cava type of Budd-Chiari syndrome after stenting in China: A retrospective analysis of a large cohort.

OBJECTIVES: To explore the risk factors for recurrence of inferior vena cava (IVC)-type Budd-Chiari syndrome (BCS) after stenting and evaluate the feasibility and primary outcomes of endovascular therapies for recurrent BCS. METHODS: A retrospective analysis of 219 patients was performed to identify risk factors for recurrence. The images of the recurrent patients during follow-up duration and interventional surgery were also reviewed to find the possible reasons of recurrence. The outcome of endovascular therapies for recurrent BCS was evaluated by Kaplan-Meier analysis. RESULTS: Among the 219 patients, 172 patients with primary IVC-type BCS underwent stenting and 28 patients experienced recurrence. Multivariate analysis identified age, Child-Pugh score, MELD and total bilirubin as independent recurrent indicators. Possible causes of recurrence include thrombosis in the stent, re-obstruction in or above the stent, and stent-related hepatic vein obstruction. Twenty-five patients with recurrent BCS underwent endovascular therapies with a few complications and achieved a high level of short- and mid-term patency. CONCLUSION: Age, total bilirubin and severity of liver function are the main risk factors for BCS recurrence. These risks might contribute to thrombosis or subsequent fibrous obstruction. Endovascular therapies are effective and safe management options that yield positive outcomes for recurrent BCS. KEY POINTS: • Risk factors for recurrent Budd-Chiari syndrome were identified by multivariate analysis. • Causes of recurrent Budd-Chiari syndrome were investigated by assessing radiological images. • There is a correlation between risk factors and causes of recurrence. • Endovascular therapies for recurrent Budd-Chiari syndrome are effective and safe.

O-6-methylguanine-DNA Methyltransferase Inhibits Gastric Carcinoma Cell Migration and Invasion by Downregulation of Matrix Metalloproteinase 2.

MGMT plays a key role in many kinds of cancers. However, the molecular mechanisms of MGMT involvement in gastric cancer (GC) are poorly elucidated. Here, we investigated the role of MGMT in GC cell migration, invasion and metastatic potential. Our data showed that MGMT expression was negatively correlated with lymph node metastasis and late TNM stages. These findings were accompanied by downregulation of matrix metalloproteinase 2 (MMP2). Loss of MGMT expression induced increases in GC cell metastasis and invasion potential in vitro and in vivo. These effects were reversed by inhibition of MGMT and MMP2. MGMT overexpression downregulated MMP2 protein levels, whereas this effect was counteracted by MGMT siRNA. In summary, MGMT is involved in gastric carcinogenesis via downregulation of MMP2. The MGMT/MMP2 pathway plays an essential role in GC metastasis and may be a potential therapeutic target for GC treatment.

MicroRNA-183 Functions As an Oncogene by Regulating PDCD4 in Gastric Cancer.

MicroRNA-183 (miR-183) has recently been identified to be implicated in a variety of critical processes in multiple human malignancies, and its fuction has been poorly characterized in gastric cancer (GC). Here we reported that miR-183 was markedly over-expressed in GC and its up-regulation was markedly associated with GC clinicopathologicalcharacters. Endogenous miR-183 was inhibited in GC cells, which dramatically attenuated cell proliferation, colony formation, migration, invasion and adhesion and enhancedGC cells apoptosis in vitro. Furthermore, in this study we demonstrated that the tumor suppressor gene PDCD4 was a target of miR-183 in GC. Collectively, these observations showed that miR-183 maybe function as an oncogene by regulating GC cell proliferation, apoptosis and metastasis and the oncogenic effect of miR-183 may relate the direct targeting PDCD4.

Autophagy protein 5 enhances the function of rat EPCs and promotes EPCs homing and thrombus recanalization via activating AKT.

Deep venous thrombosis (DVT) is one of the most common peripheral vascular diseases. The roles of bone marrow-derived endothelial progenitor cells (EPCs) on the recanalization of venous thrombosis has been suggested recently, while the underlying mechanisms are not completely understood. Our objective was to investigate the functions of autophagy protein 5 (ATG5) in rat EPCs and its potential application in DVT. We have found that silencing of ATG5 or pharmacological suppression of ATG5 in rat EPCs reduces both the migration and psudotube formation under hypoxia in vitro. In line, overexpression of ATG5 significantly enhances the EPCs migration and psudotube formation capabilities. More importantly, injection of EPCs that stably express ATG5 increases EPC homing to the ischemic site and promotes thrombus recanalization in a rat DVT model in vivo. Mechanistically, we have shown that ATG5 overexpression enhances psudotube formation via the activation of AKT. These findings suggest that ATG5-AKT signaling plays an essential role in EPC migration and psudotube formation. Regulation of ATG5-AKT signaling may provide a potential novel therapy for DVT.

Metformin regulates differentiation of bone marrow-derived endothelial progenitor cells via multiple mechanisms.

OBJECTIVE: The aim of this study was to investigate the effect of metformin on endothelial progenitor cells (EPCs) differentiation and the possible mechanisms. METHODS: EPCs were treated with metformin and differentiation, migration and tube formation of EPCs were evaluated. Moreover, we also assessed the AMPK-mTOR-p70S6K pathway, AMPK related autophagy pathway and eNOS-NO pathway to explore the mechanisms. RESULTS: Metformin treatment could significantly increase differentiation of EPCs. On the mechanisms, increased level of AMPKand eNOS phosphorylation, LC3 expression and NO production, and decreased mTOR, p70 S6K as well as TGF-ß expression were found in EPCs. The AMPK inhibitor compound C, Atg5 knocking-down and eNOS inhibitor l-NAME could reverse the effect exerted by metformin. CONCLUSIONS: Our results here showed that metformin could regulate the differentiation of EPCs. Autophagy related pathway and AMPK-eNOS-NO pathway were involved in the mechanisms.

Safety and Efficacy of Low Dosage of Urokinase for Catheter-directed Thrombolysis of Deep Venous Thrombosis.

BACKGROUND: Catheter-directed thrombolysis (CDT) has been a mainstay in treating deep venous thrombosis (DVT). However, the optimal dosage of a thrombolytic agent is still controversial. The goal of this study was to evaluate the safety and efficacy of low dosage urokinase with CDT for DVT. METHODS: A retrospective analysis was performed using data from a total of 427 patients with DVT treated with CDT in our single center between July 2009 and December 2012. Early efficacy of thrombolysis was assessed with a thrombus score based on daily venography. The therapeutic safety was evaluated by adverse events. A venography or duplex ultrasound was performed to assess the outcome at 6 months, 1 year and 2 years postoperatively. RESULTS: The mean total dose of 3.34 (standard deviation [SD] 1.38) million units of urokinase was administered during a mean of 5.18 (SD 2.28) days. Prior to discharge, Grade III (complete lysis) was achieved in 154 (36%) patients; Grade II (50-99% lysis) in 222 (52%); and Grade I (50% lysis) in 51 (12%). The major complications included one intracranial hemorrhage, one hematochezia, five gross hematuria, and one pulmonary embolism. Moreover, no death occurred in the study. CONCLUSIONS: Treatment of low-dose catheter-directed thrombosis is an efficacious and safe therapeutic approach in patients with DVT offering good long-term outcomes and minimal complications.

Biocompatibility of porcine small intestinal submucosa and rat endothelial progenitor cells in vitro.

OBJECTIVE: This study investigated the biocompatibility of the small intestinal submucosa (SIS) and endothelial progenitor cells (EPCs) by co-cultivating EPCs and SIS in vitro and observing EPC growth on the SIS. METHODS: The porcine SIS was prepared and bone marrow mononuclear cells (BMMNCs) were isolated from 3 or 4-week old male SD rats. Cellular morphology was observed by light microscopy and scanning electron microscopy (SEM) and viabilities by the MTT assays. Endothelial progenitor cells (EPCs) were phenotyped by immunocytochemistry, immunofluorescence microscopy and flow cytometry. Vascular lumen formation was evaluated by the Matrigel tube formation assays. EPCs were seeded onto the SIS and production of angiogenin-1 and endothelial cell growth factor (VEGF) by EPCs was examined by ELISA and immunoblotting assays. RESULTS: Light microscopy and SEM showed that the mechanically and chemically treated small intestinal submucosa was composed of cell-free extracellular matrix. Immunohistochemistry, and flow cytometry revealed that the EPCs expressed appropriate surface markers including CD34, CD133, and VEGFR-2. Furthermore, the EPCs formed lumen-like structures and the SIS significantly enhanced the growth of EPCs in vitro. CONCLUSION: SIS has good biocompatibility with EPCs. SIS pre-seeded with EPCs can be potentially applied as an alternative scaffold material in artificial blood vessel prosthesis.

Upregulation of MicroRNA-126 Contributes to Endothelial Progenitor Cell Function in Deep Vein Thrombosis via Its Target PIK3R2.

Deep vein thrombosis (DVT) is a common complication of surgery. Endothelial progenitor cells (EPCs) are recruited into resolving venous thrombi. In this report, we investigated the effects of miR-126 on EPCs function and venous thrombus resolution. We demonstrated that overexpression of miR-126 enhanced EPCs' migration and tubulogenic activity in vitro, and promoted EPCs' homing and thrombus resolving in vivo. Moreover, we identified that miR-126 directly targeted PIK3R2 and affected PI3K/Akt signaling axis. Overall, our findings demonstrated that miR-126 promoted EPCs function through suppressing PIK3R2 expression and modulation of miR-126 may represent a potential therapeutic intervention for treating DVT.

HMGB1 Silencing Potentiates the Anti-inflammatory Effects of Sodium Ferulate in ox-LDL-Stimulated Vascular Smooth Muscle Cells.

Atherosclerosis is a sustained inflammatory disease of the arterial wall. The purpose of the current study is to investigate the effect of sodium ferulate on the proliferation and migration of human vascular smooth muscle cells (hVSMCs). In addition, we also sought to determine whether HMGB1 knockdown could potentiate the anti-inflammatory effects of sodium ferulate. hVSMCs were treated with oxidized lower-density lipoprotein (ox-LDL, 50 mg/l) to induce inflammation. Cells were then treated with sodium ferulate and HMGB1 silencing (SiHMGB1) individually or in combination. The phenotypes of the treated cells including proliferation, cell cycle profile, apoptosis, and gene expression were analyzed. Results showed that sodium ferulate or SiHMGB1 treatment inhibited ox-LDL-induced inflammation in hVSMCs. Furthermore, the combination of SiHMGB1 plus sodium ferulate treatment displayed an additive effect in inhibiting the proliferation and migration of hVSMCs. Consistently, the suppression of receptor for advanced glycation end products expression was also observed. ICAM-1 and transforming growth factor-ß suggest that these signaling components were involved in the anti-inflammatory effect. Our study confirms the anti-inflammatory function of sodium ferulate, and uncovered the potentiating effect of HMGB1 knockdown in suppressing ox-LDL-induced proliferation and migration of hVSMCs. Inhibition of HMGB1 expression in addition to sodium ferulate treatment might be a more effective therapeutic approach for atherosclerosis.