Background Preterm birth complications are one of the leading causes of death among children under 5 years of age. Despite advances in medical care, many survivors face a lifetime of disability, including mental and physical retardation, and chronic lung disease. More recently, both allogenic and autogenic cord blood cells have been applied in the treatment of neonatal conditions such as hypoxic-ischemic encephalopathy (HIE) and bronchopulmonary dysplasia (BPD). Objective To assess the safety of autologous, volume- and red blood cell- (RBC-) reduced, noncryopreserved umbilical cord blood (UCB) cell infusion to preterm infants. Method This study was a phase I, open-label, single-arm, single-center trial to evaluate the safety of autologous, volume- and RBC-reduced, noncryopreserved UCB cell (5 × 107cells/kg) infusion for preterm infants <37 weeks gestational age. UCB cell characteristics, pre- and postinfusion vital signs, and laboratory investigations were recorded. Clinical data including mortality rates and preterm complications were recorded. Results After processing, (22.67 ± 4.05) ml UCB cells in volume, (2.67 ± 2.00) × 108 cells in number, with (22.67 ± 4.05) × 106 CD34+, (3.72 ± 3.25) × 105 colony forming cells (CFU-GM), and (99.7 ± 0.17%) vitality were infused to 15 preterm infants within 8 hours after birth. No adverse effects were noticed during treatment. All fifteen patients who received UCB infusion survived. The duration of hospitalization ranged from 4 to 65 (30 ± 23.6) days. Regarding preterm complications, no BPD, necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP) was observed. There were 1/15 (7%) infant with intraventricular hemorrhage (IVH), 5/15 (33.3%) infants with ventilation-associated pneumonia, and 10/15 (66.67%) with anemia, respectively. Conclusions Collection, preparation, and infusion of fresh autologous UCB cells to preterm infants is feasible and safe. Adequately powered randomized controlled studies are needed.

No abstract

Tumor cells transform into endothelial cells by epithelial-to-mesenchymal transition, which is characterized by vasculogenic mimicry (VM). VM not only accelerates tumor progression but also increases drug-induced resistance. However, very little is currently known about the molecular determinants that enable VM. Targeting VM might bring a new breakthrough in cancer treatment. Thrombin is the key enzyme of the blood coagulation system and could contribute to tumor progression. Nevertheless, the association between thrombin and VM formation remains largely unknown. We found that VM was associated with the overall survival of non-small-cell lung cancer (NSCLC) patients, and that thrombin expression was closely related to VM formation. This research revealed that thrombin induced VM formation via PAR-1-mediated NF-κB signaling cascades. The novel thrombin inhibitors r-hirudin and DTIP inhibited VM formation and spontaneous metastases in subcutaneous tumors. Clinical pathological analysis confirmed that NSCLC patients with thrombin-positive/PAR-1-high expression had the poorest prognosis and were the most likely to form VM. The promotional activity of thrombin in VM formation and tumor metastasis was abolished in PAR-1deficient NSCLC cells. The EGFR inhibitor gefitinib had no effect on VM and increased VEGF expression in tumors. The combination therapy of DTIP and gefitinib achieved a better therapeutic effect than either agent alone. This study is the first to illustrate that thrombin substantially contributes, together with PAR-1, to VM formation and to illustrate that VM might be a target of r-hirudin and DTIP to suppress tumor progression. The anticoagulants r-hirudin and DTIP could be employed for antitumor therapy. Combination therapy with DTIP with an EGFR inhibitor might achieve superior therapeutic effects.

Tumor growth, especially in the late stage, requires adequate nutrients and rich vasculature, in which PKM2 plays a convergent role. It has been reported that PKM2, together with FOXM1D, is upregulated in late-stage colorectal cancer and associated with metastasis; however, their underlying mechanism for promoting tumor progression remains elusive. Herein, we revealed that FOXM1D potentiates PKM2-mediated glycolysis and angiogenesis through multiple protein-protein interactions. In the presence of FBP, FOXM1D binds to tetrameric PKM2 and assembles a heterooctamer, restraining PKM2 metabolic activity by about a half and thereby promoting aerobic glycolysis. Furthermore, FOXM1D interacts with PKM2 and NF-jB and induces their nuclear translocation with the assistance of the nuclear transporter importin 4. Once in the nucleus, PKM2 and NF-jB complexes subsequently augment VEGFA transcription. The increased VEGFA is secreted extracellularly via exosomes, an event potentiated by the interaction of FOXM1 with VPS11, eventually promoting tumor angiogenesis. Based on these findings, our study provides another insight into the role of PKM2 in the regulation of glycolysis and angiogenesis.

With fewer repeated surgical procedures, higher EQ, and comparable total costs, PCNL is recommended as the first choice for the treatment of large renal calculi in patients with a solitary kidney. As for specific indications such as anticoagulant drugs, RIRS is a safer choice with fewer complications and acceptable final stone-free rate.

No abstract

For the first time, we have shown that AGXT2L1 is down-regulated in HCC and its low expression indicates a poor prognosis. Our findings also demonstrated that AGXT2L1 is a crucial gene in the abnormal lipogenesis of HCC tissue.

Suicide and associated behaviors represent a significant health disparity among refugees and displaced persons. Despite this burden, evidence for prevention programing in these populations is limited. This study aimed to inform the selection and implementation of suicide prevention strategies in refugee camps in Northwestern, Thailand—camps that had experienced recent spikes in suicides and suicide attempts at the time of the study. We leveraged community-based system dynamics (CBSD) modeling through a series of four workshops with key local stakeholders and suicide prevention experts, to build a qualitative systems model that accounts for complexities and is aimed at assisting local partners with selecting the most promising strategies for implementation and evaluation. The process expanded local understanding of the causes and consequences of suicide and resulted in selection of priority interventions aimed at reducing suicide in this context. Our research illustrates the application of a novel methodology that aims to account for the complexities of suicide prevention in the context of displacement and helps to optimize local suicide prevention efforts.