A bypass flow model to study endothelial cell mechanotransduction across diverse flow environments.

Disturbed flow is one of the pathological initiators of endothelial dysfunction in intimal hyperplasia (IH) which is commonly seen in vascular bypass grafts, and arteriovenous fistulas. Various in vitro disease models have been designed to simulate the hemodynamic conditions found in the vasculature. Nonetheless, prior investigations have encountered challenges in establishing a robust disturbed flow model, primarily attributed to the complex bifurcated geometries and distinctive flow dynamics. In the present study, we aim to address this gap by introducing an in vitro bypass flow model capable of inducing disturbed flow and other hemodynamics patterns through a pulsatile flow in the same model. To assess the model's validity, we employed computational fluid dynamics (CFD) to simulate hemodynamics and compared the morphology and functions of human umbilical venous endothelial cells (HUVECs) under disturbed flow conditions to those in physiological flow or stagnant conditions. CFD analysis revealed the generation of disturbed flow within the model, pinpointing the specific location in the channel where the effects of disturbed flow were observed. High-content screening, a single-cell morphological profile assessment, demonstrated that HUVECs in the disturbed flow area exhibited random orientation, and morphological features were significantly distinct compared to cells in the physiological flow or stagnant condition after a two days of flow exposure. Furthermore, HUVECs exposed to disturbed flow underwent extensive remodeling of the adherens junctions and expressed higher levels of endothelial cell activation markers compared to other hemodynamic conditions. In conclusion, our in vitro bypass flow model provides a robust platform for investigating the associations between disturbed flow pattern and vascular diseases.

Outcomes of early cannulation arteriovenous graft versus PTFE arteriovenous graft in hemodialysis patients: A meta-analysis and systematic review.

Arteriovenous graft (AVG) is an alternative for hemodialysis (HD) patients with end-stage renal disease when their permanent vascular accesses fail. Since the last decades, the most widely used materials in these patients have been polytetrafluoroethylene (PTFE)-AVGs. Recently, several studies have reported that early cannulation (EC)-AVG can be an alternative to PTFE-AVG. This systematic review and meta-analysis aimed to compare the outcomes of EC-AVG and PTFE-AVG in HD patients. We searched the Ovid Embase, Ovid MEDLINE, and Cochrane Central Register of Controlled Trials for the relevant studies published from 01.01.2000 to 19.12.2022 by keywords and free words. All randomized controlled trials (RCTs) and observational cohort studies comparing EC-AVG with PTFE-AVG were included. Ten studies were included in analysis: one RCT, six retrospective cohort studies, and three prospective cohort studies. The results showed shorter cannulation intervals (four studies, 1116 participants: mean difference -23.62 days, 95% CI [-32.03, -15.21], p < 0.05) and less central venous catheter (CVC) usage (four studies, 733 participants: OR 0.20, 95% CI [0.04, 0.92], p < 0.05) for EC-AVG compared with PTFE-AVG, while comparable outcomes of primary patency (eight studies, 1712 participants: HR 0.89, 95% CI [0.70, 1.12]), primary assisted patency (five studies, 1355 participants: HR 1.13, 95% CI [0.70, 1.84]), secondary patency (nine studies, 1920 participants: HR 0.93, 95% CI [0.66, 1.31]), and infection risk (four studies, 640 participants: HR 1.12, 95% CI [0.48, 2.58]). When compared to PTFE-AVG in HD patients, EC-AVG seems to exhibit shorter cannulation intervals, less CVC usage, and comparable outcomes of graft patency, and infection risk.

[The Best Time of Minimal Residual Disease Monitoring for Predicting Survival and Prognosis in Children with T-Cell Acute Lymphoblastic Leukemia].

OBJECTIVE: To investigate the optimal time of monitoring minimal residual disease (MRD) for predicting survival and prognosis in children with T-cell acute lymphoblastic leukemia (T-ALL) after treated by CCLG-ALL2008 chemotherapy. METHODS: 96 children with T-ALL receiving CCLG-ALL2008 chemotherapy treated in our hospital from January 2015 to January 2020 were retrospectively summarized. The follow-up time was 9.0-65.0 months, with a median of 43.5 months. Kaplan-Meier survival curve was used to detect the overall event-free survival (EFS) and overall survival (OS) of the patients. The clinical data, MRD levels after 15 d, 33 d and 90 d chemotherapy between EFS group and relapse group, as well as OS group and death group were compared by using univariate analysis. Multivariate Logistic regression analysis was used to screen the main risk factors affecting EFS and OS of the patients. The patients were divided into low, moderate and high-risk according to the MRD level after 15 d, 33 d and 90 d, the differences of EFS and OS between each groups were compared again. RESULTS: By the end of follow-up, 50 patients recurred and other 46 patients non-recurred; 40 patients died and 56 patients survived, the EFS was (49.5±6.3)% and OS was (61.5±5.9)%. Univariate analysis showed that the initial WBC count in EFS group (n=46) was significantly lower than that in relapse group (n=50), and MRD levels after 33 d and 90 d were significantly less also (P<0.05). Prednisone response in OS group (n=56) was better than that in death group (n=40), and central nerve invasion rate was lower, MRD level after 33 and 90 d were lower (P<0.05). Logistic regression analysis showed that MRD level after 90 d was the main risk factor affecting EFS of the patients; prednisone reaction, central nerve invasion and MRD level after 90 d were the main risk factors affecting OS of the patients (P<0.05). There were no differences of EFS or OS between the groups according to the MRD levels after 15 and 33 d (P>0.05), however for 90 d, EFS and OS of the patients in high-risk group were significantly lower than those in medium-risk group, and those in medium-risk group were lower than those in low-risk group (P<0.05). CONCLUSION: The MRD level after 90 days CCLG-ALL2008 chemotherapy may be the best time to predict the survival and prognosis in T-ALL children.

Human embryonic mesenchymal stem cells alleviate pathologic changes of MRL/Lpr mice by regulating Th7 cell differentiation.

Recent evidence indicates that mesenchymal stem cells (MSC) derived from early embryonic tissues have better therapeutic ability as compared with adult tissue-derived stem cells. In the present study, we transplanted human early embryonic MSC (hMSC) into MRL/Lpr mice via tail vein injection to observe the therapeutic efficacy of hMSC and their impact on T helper 17 (Th17) cell differentiation in MRL/Lpr mice. Animals in hMSC treatment group received hMSC (1 × 106/200 µL) via the tail vein at the age of 16 and 19 weeks. We found that hMSC treatment prolonged the survival of MRL/Lpr mice without inducing tumorigenesis, reduced urine protein, and alleviated the renal pathologic changes. In addition, it reduced the proportion of Th17 cells in the spleen of MRL/Lpr mice and the serum interleukin 17 (IL-17) concentration. Our in vitro experiment also demonstrated that hMSC could secrete Th17 differentiation-related cytokines of PGE2, IL-10 and TGF-ß, and IFN-γ stimulation up-regulated the secretion of these immune regulating factors. The results of the present study suggest that hMSC therapy could alleviate systemic and local renal lesions in MRL/Lpr mice, probably by secreting immune regulating factors and regulating Th17 cell differentiation in MRL/Lpr mice.