circ_PPAPDC1A promotes Osimertinib resistance by sponging the miR-30a-3p/ IGF1R pathway in non-small cell lung cancer (NSCLC).

BACKGROUND: Recent evidence has demonstrated that abnormal expression and regulation of circular RNA (circRNAs) are involved in the occurrence and development of a variety of tumors. The aim of this study was to investigate the effects of circ_PPAPDC1A in Osimertinib resistance in NSCLC. METHODS: Human circRNAs microarray analysis was conducted to identify differentially expressed (DE) circRNAs in Osimertinib-acquired resistance tissues of NSCLC. The effect of circ_PPAPDC1A on cell proliferation, invasion, migration, and apoptosis was assessed in both in vitro and in vivo. Dual-luciferase reporter assay, RT-qPCR, Western-blot, and rescue assay were employed to confirm the interaction between circ_PPAPDC1A/miR-30a-3p/IGF1R axis. RESULTS: The results revealed that circ_PPAPDC1A was significantly upregulated in Osimertinib acquired resistance tissues of NSCLC. circ_PPAPDC1A reduced the sensitivity of PC9 and HCC827 cells to Osimertinib and promoted cell proliferation, invasion, migration, while inhibiting apoptosis in Osimertinib-resistant PC9/OR and HCC829/OR cells, both in vitro and in vivo. Silencing circ_PPAPDC1A partially reversed Osimertinib resistance. Additionally, circ_PPAPDC1A acted as a competing endogenous RNA (ceRNA) by targeting miR-30a-3p, and Insulin-like Growth Factor 1 Receptor (IGF1R) was identified as a functional gene for miR-30a-3p in NSCLC. Furthermore, the results confirmed that circ_PPAPDC1A/miR-30a-3p/IGF1R axis plays a role in activating the PI3K/AKT/mTOR signaling pathway in NSCLC with Osimertinib resistance. CONCLUSIONS: Therefore, for the first time we identified that circ_PPAPDC1A was significantly upregulated and exerts an oncogenic role in NSCLC with Osimertinib resistance by sponging miR-30a-3p to active IGF1R/PI3K/AKT/mTOR pathway. circ_PPAPDC1A may serve as a novel diagnostic biomarker and therapeutic target for NSCLC patients with Osimertinib resistance.

Association between pretreatment emotional distress and immune checkpoint inhibitor response in non-small-cell lung cancer.

Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical studies have explored its relationship with response to immune checkpoint inhibitors (ICIs). Here we report results from cohort 1 of the prospective observational STRESS-LUNG study, which investigated the association between ED and clinical efficacy of first-line treatment of ICIs in patients with advanced non-small-cell lung cancer. ED was assessed by Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale. The study included 227 patients with 111 (48.9%) exhibiting ED who presented depression (Patient Health Questionnaire-9 score ≥5) and/or anxiety (Generalized Anxiety Disorder 7-item score ≥5) symptoms at baseline. On the primary endpoint analysis, patients with baseline ED exhibited a significantly shorter median progression-free survival compared with those without ED (7.9 months versus 15.5 months, hazard ratio 1.73, 95% confidence interval 1.23 to 2.43, P = 0.002). On the secondary endpoint analysis, ED was associated with lower objective response rate (46.8% versus 62.1%, odds ratio 0.54, P = 0.022), reduced 2-year overall survival rate of 46.5% versus 64.9% (hazard ratio for death 1.82, 95% confidence interval 1.12 to 2.97, P = 0.016) and detriments in quality of life. The exploratory analysis indicated that the ED group showed elevated blood cortisol levels, which was associated with adverse survival outcomes. This study suggests that there is an association between ED and worse clinical outcomes in patients with advanced non-small-cell lung cancer treated with ICIs, highlighting the potential significance of addressing ED in cancer management. ClinicalTrials.gov registration: NCT05477979 .

Erratum: [Corrigendum] Chloroquine potentiates the anticancer effect of sunitinib on renal cell carcinoma by inhibiting autophagy and inducing apoptosis.

[This corrects the article DOI: 10.3892/ol.2017.7635.].

Downregulation of miR-503-5p Promotes the Development of Pancreatic Cancer by Targeting Cyclin E2.

This study aimed to elucidate the role of microRNA-503 (miR-503) in pancreatic cancer (PC) progression and the underlying regulatory mechanisms. We acquired miR-503-3p and miR-503-5p expression data along with survival times of PC and normal samples from the UCSC Xena database. Using the t-test, we compared the expression of miR-503-3p and miR-503-5p between PC and normal samples, and evaluated their prognostic significance via Kaplan-Meier survival analysis. The expression of miR-503-5p in PC cells was detected by quantitative PCR. We subsequently overexpressed miR-503-5p in PC cells and examined cell viability, apoptosis, and migration through CCK8 assay, flow cytometry, and Transwell assay, respectively. Potential functional targets were identified using miRTarBase and validated by dual-luciferase reporter assay. Both miR-503-3p and miR-503-5p expression were found to be downregulated in PC; however, only miR-503-5p was linked to cancer prognosis based on public data. In vitro experiments demonstrated that overexpression of miR-503-5p substantially decreased cell viability, induced apoptosis, caused G0/G1 arrest, and inhibited cell migration. miR-503-5p was found to target cyclin E2 (CCNE2), and overexpression of CCNE2 could counteract the effects of miR-503-5p on PC cells. Conclusion: The downregulation of miR-503-5p enhances the progression of PC by targeting CCNE2. The detection of miR-503-5p expression may provide valuable insights for the prevention and prognostic evaluation of PC.

Association between postoperative ibuprofen exposure and acute kidney injury after pediatric cardiac surgery.

BACKGROUND: Acute kidney injury (AKI) is a common complication after pediatric cardiac surgery and is associated with worse outcomes. Ibuprofen is widely used in the perioperative period and can affect kidney function in children. However, the association between ibuprofen exposure and AKI after pediatric cardiac surgery has not been determined yet. METHODS: In this retrospective cohort study, children undergoing cardiac surgery with cardiopulmonary bypass were studied. Exposure was defined as given ibuprofen in the first 7 days after surgery. Postoperative AKI was diagnosed using the KDIGO criteria. A multivariable Cox regression model was used to assess the association between ibuprofen exposure and postoperative AKI by taking ibuprofen as a time-varying covariate. RESULTS: Among 1,112 included children, 198 of them (17.8%) experienced AKI. In total, 396 children (35.6%) were exposed to ibuprofen. AKI occurred less frequently among children who were administered ibuprofen than among those who were not (46 of 396 [11.6%] vs. 152 of 716 [21.2%], p < 0.001). Using the Cox regression model accounting for time-varying exposures, ibuprofen treatment was not associated with AKI (adjusted HR, 0.99; 95% CI 0.70-1.39, p = 0.932). This insignificant association was consistent across the sensitivity and subgroup analyses. CONCLUSIONS: Postoperative ibuprofen exposure in pediatric patients undergoing cardiac surgery was not associated with an increased risk of AKI.

Development and Validation of a Nomogram for Predicting Acute Kidney Injury in Pediatric Patients Undergoing Cardiac Surgery.

Acute kidney injury (AKI) is a common complication after cardiac surgery and associated with adverse outcomes. The purpose of this study is to construct a nomogram to predict the probability of postoperative AKI in pediatric patients undergoing cardiac surgery. We conducted a single-center retrospective cohort study of 1137 children having cardiac surgery under cardiopulmonary bypass. We randomly divided the included patients into development and validation cohorts at a ratio of 7:3. The least absolute shrinkage and selection operator regression model was used for feature selection. We constructed a multivariable logistic regression model to select predictors and develop a nomogram to predict AKI risk. Discrimination, calibration and clinical benefit of the final prediction model were evaluated in the development and validation cohorts. A simple nomogram was developed to predict risk of postoperative AKI using six predictors including age at operation, cyanosis, CPB duration longer than 120 min, cross-clamp time, baseline albumin and baseline creatinine levels. The area under the receiver operator characteristic curve of the nomogram was 0.739 (95% CI 0.693-0.786) and 0.755 (95% CI 0.694-0.816) for the development and validation cohort, respectively. The calibration curve showed a good correlation between predicted and observed risk of postoperative AKI. Decision curve analysis presented great clinical benefit of the nomogram. This novel nomogram for predicting AKI after pediatric cardiac surgery showed good discrimination, calibration and clinical practicability.

Postoperative elevated cardiac troponin levels predict all-cause mortality and major adverse cardiovascular events following noncardiac surgery: A dose-response meta-analysis of prospective studies.

STUDY OBJECTIVE: To perform a dose-response meta-analysis for the association between postoperative myocardial injury (PMI) in noncardiac surgery and the risk of all-cause mortality or major adverse cardiovascular event (MACE). DESIGN: Dose-response meta-analysis of prospective studies with weighted (WL) or generalized (GL) linear and restricted cubic spline (RCS) regression. SETTING: Teaching hospitals. PATIENTS: Adult patients undergoing noncardiac surgery. INTERVENTIONS: No. MEASUREMENTS: The primary outcome was all-cause mortality. The secondary outcome was MACE. MAIN RESULTS: 29 studies (53,518 patients) were included. The overall incidence of PMI was 26.0% (95% CI 21.0% to 32.0%). Compared to those without PMI, patients with PMI had an increased risk of all-cause mortality at short- (<12 months) (cardiac troponin[cTn]I: unadj OR 1.71,95%CI 1.22 to 2.41, P < 0.001; cTnT: unadj OR 2.33,95%CI 2.07 to 2.63, P < 0.001), and long-term (≥ 12 months) (cTnI: unadj OR 1.80, 95%CI 1.63 to 1.99; cTnT: unadj OR 1.47,95%CI 1.33 to 1.62) (All P < 0.001) follow-up. For MACE, the group with elevated values was associated with an increased risk (cTnI: unadj OR 1.98, 95% CI 1.13 to 3.47, P = 0.018; cTnT: unadj OR 2.29, 95% CI 1.88 to 2.79, P < 0.001). Dose-response analysis showed positive associations between PMI (per 1× upper reference limit[URL] increment) and all-cause mortality both at short- (unadj OR) (WL, OR 1.09, 95% CI 1.09 to 1.10; GL, OR 1.06, 95% CI 1.06 to 1.07; RCS in the range of 1-2× URL, OR = 2.43, 95%CI 2.25 to 2.62) and long-term follow-up (unadj HR) (WL, OR 1.16, 95% CI 1.14 to 1.17; GL, OR 1.15, 95% CI 1.13 to 1.16; RCS in the range of 1-2.75× URL, OR = 1.23, 95%CI 1.13 to 1.33), and MACE at longest follow-up (unadj OR) (WL: OR 1.53, 95% CI 1.49 to 1.57; GL: OR 1.46, 95% CI 1.42 to 1.50; RCS in the range of 1-2 x URL, OR = 3.10, 95%CI 2.51 to 3.81) (All P < 0.001). For mild cTn increase below URL, the risk of mortality increased with every increment of 0.25xURL (WL, OR 1.03, 95% CI 1.02 to 1.03; GL, OR 1.05, 95% CI 1.03 to 1.07; RCS in the range of 0-0.5 URL, OR = 9.41, 95% CI 7.41 to 11.95) (All P < 0.001). CONCLUSIONS: This study shows positive WL or GL and RCS dose-response relationships between PMI and all-cause mortality at short (< 12 mons)- and long-term (≥ 12 mons) follow-up, and MACE at longest follow-up. For mild cTn increase below URL, the risk of mortality also increases even with every increment of 0.25× URL.

Ultrasound-assisted extraction optimization of polyphenols from Boletus bicolor and evaluation of its antioxidant activity.

Introduction: Boletus bicolor (B. bicolor) mushrooms are widely consumed as a valuable medicinal and dietary ingredient in China, but the active ingredients of this mushroom and their extraction methods were not extensively studied. Methods: In this paper, we propose an optimized ultrasound-assisted extraction (UAE) method to detect natural antioxidant substances in B. bicolor. The antioxidants were quantitatively and quantitatively determined using UPLC-MS, the polyphenols were evaluated based on response surface methodology (RSM), and density functional theory (DFT) calculations were performed. Results: The results showed that the optimal extraction was obtained under the following conditions: ethanol concentration 42%; solvent to solid ratio 34:1 mL/g; ultrasonic time 41 min; and temperature 40°C. The optimized experimental polyphenol value obtained under these conditions was (13.69 ± 0.13) mg/g, consistent with the predicted value of 13.72 mg/g. Eight phenolic compounds in the extract were identiffed by UPLC-MS: syringic acid, chlorogenic acid, gallic acid, rosmarinic acid, protocatechuic acid, catechin, caffeic acid, and quercetin. Chlorogenic acid exhibits the highest HOMO energy (-0.02744 eV) and the lowest energy difference (-0.23450 eV) among the studied compounds, suggesting that the compound might be the strongest antioxidant molecule. Eight phenolic compounds from the B. bicolor signiffcantly inhibited intracellular reactive oxygen species (ROS) generation, reduced oxidative stress damage in H2O2-induced HepG-2 cells. Discussion: Therefore, it was confirmed that the UAE technique is an efficient, rapid, and simple approach for extracting polyphenols with antioxidant activity from B. bicolor.

VIM­AS1 promotes proliferation and drives enzalutamide resistance in prostate cancer via IGF2BP2­mediated HMGCS1 mRNA stabilization.

VIM­AS1, a cancer­specific long non­coding RNA, has been recognized as a pivotal regulator in multiple types of cancer. However, the role of VIM­AS1 in the proliferation and resistance to anti­androgen therapy of LNCaP and C4­2 prostate cancer cells remains to be determined. In the current study, gain­and­loss experiments were used to investigate the effects of VIM­AS on the proliferation and anti­androgen therapy of LNCaP and C4­2 cells. RNA sequencing, RNA pulldown and RNA immunoprecipitation were used to elucidate the underlying mechanism of VIM­AS1 driving prostate progression. It was demonstrated that VIM­AS1 was upregulated in C4­2 cells, an established castration­resistant prostate cancer (CRPC) cell line, compared with in LNCaP cells, an established hormone­sensitive prostate cancer cell line. The present study further demonstrated that VIM­AS1 was positively associated with the clinical stage of prostate cancer. Functionally, overexpression of VIM­AS1 decreased the sensitivity to enzalutamide treatment and enhanced the proliferation of LNCaP cells in vitro, whereas knockdown of VIM­AS1 increased the sensitivity to enzalutamide treatment and reduced the proliferation of C4­2 cells in vitro and in vivo. Mechanistically, 3­hydroxy­3­methylglutaryl­CoA synthase 1 (HMGCS1) was identified as one of the direct downstream targets of VIM­AS1, and VIM­AS1 promoted HMGCS1 expression by enhancing HMGCS1 mRNA stability through a VIM­AS1/insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2)/HMGCS1 RNA­protein complex. Rescue assays indicated that knockdown of HMGCS1 expression ameliorated the increase in proliferation and enzalutamide resistance of prostate cancer cells induced by VIM­AS1 overexpression. Overall, the present study determined the roles and mechanism of the VIM­AS1/IGF2BP2/HMGCS1 axis in regulating proliferation and enzalutamide sensitivity of prostate cancer cells and suggested that VIM­AS1 may serve as a novel therapeutic target for the treatment of patients with CRPC.

Interaction between Illite and a Pseudomonas stutzeri-Heavy Oil Biodegradation Complex.

Illite is a widely distributed clay mineral with huge reserves in Earth's crust, but its effect on heavy oil biodegradation is rarely reported. This study made an investigation of the interactions between illite and a Pseudomonas stutzeri-heavy oil complex (PstHO). Results showed that, although illite exerted a negative effect on P. stutzeri degrading heavy oil by inhibiting the biodegradation of 64 saturated hydrocarbons (SHs) and 50 aromatic hydrocarbons (AHs), it selectively stimulated the biodegradation of 45 AHs with a specific structure, and its biogenic kaolinization at room temperature (35 °C) and pressure (1 atm) was observed in PstHO for the first time. The finding points out for the first time that, in PstHO, illite may change the quasi-sequential of AHs biodegradation of heavy oil, as well as its kaolinization without clay intermediate.

Association of early postoperative serum magnesium with acute kidney injury after cardiac surgery.

INTRODUCTION: Dysmagnesemia has been demonstrated to be involved in the pathophysiology of kidney diseases and is common in cardiac surgical patients. It remains unknown whether changes of serum magnesium after cardiac surgery affect AKI. We aimed to investigate the association of early postoperative magnesium with cardiac surgery-associated AKI in adults. METHODS: We conducted a multicenter retrospective cohort study involving patients who underwent cardiac surgery in the eICU Collaborative Research Database between 2014 and 2015. AKI within 7 days after surgery was defined using both serum creatinine and urine output criteria of Kidney Disease Improving Global Outcomes definition. Postoperative AKI was analyzed using multivariable logistic regression with early postoperative serum magnesium measured within the first 24 h after surgery as a continuous variable and categorically by quartiles. RESULTS: Postoperative AKI was identified in 3498 of 6124 (57.1%) patients receiving cardiac surgery. The median (25th-75th percentiles) early postoperative serum magnesium level of the study population was 2.3 (2.0-2.7) mg/dL. Higher serum magnesium level was associated with a higher risk of developing postoperative AKI (adjusted odds ratio (OR), 1.46 per 1 mg/dL increase; 95% confidence interval (CI), 1.31-1.62; p<.001). The multivariable-adjusted ORs (95% CIs) of postoperative AKI across increasing quartiles of serum magnesium were 1.00 (referent), 1.11 (0.95-1.29), 1.30 (1.12-1.52), and 1.72 (1.47-2.02) (p for trend <.001). CONCLUSIONS: These data demonstrate a significantly higher incidence of AKI in patients with higher early postoperative serum magnesium who underwent cardiac surgery.

Clinical presentation and in-hospital outcomes of intraoperative red blood cell transfusion in non-anemic patients undergoing elective valve replacement.

Background: Intraoperative transfusion is associated with adverse clinical outcomes in cardiac surgery. However, few studies have shown the impact of intraoperative red blood cell (RBC) transfusion on non-anemic patients undergoing cardiac surgery. We assessed the in-hospital clinical outcomes of non-anemic patients undergoing isolated valve replacements and investigated the predictors associated with intraoperative RBC transfusion. Methods: We enrolled 345 non-anemic patients undergoing isolated valve replacements in our department from January 2015 to December 2019. The patients were stratified by the receipt of intraoperative RBC transfusion. Baseline characteristics were compared between groups and multiple logistic regression was used to identify the predictors for intraoperative RBC transfusion. The association between intraoperative RBC transfusion and in-hospital outcomes was also evaluated. Results: Intraoperative RBC transfusion developed in 84 of the 345 enrolled patients (24.3%). Three independent predictors for intraoperative RBC transfusion of non-anemic patients undergoing isolated valve replacements were identified by multivariate logistic analysis, including female, iron deficiency and hemoglobin level. When the two groups were compared, a significant tendency of higher in-hospital mortality (6.0% vs. 1.1%, P = 0.033) and higher incidence of postoperative hypoxemia (9.5% vs. 2.7%, P = 0.007) were observed in the intraoperative RBC transfusion group. After adjustment, the presence of intraoperative RBC transfusion was associated with an increase in postoperative hypoxemia (OR = 3.36, 95% CI: 1.16-9.71, P = 0.026). Conclusion: Intraoperative RBC transfusion was associated with poorer clinical outcomes in non-anemic adults undergoing isolated valve replacements, which significantly increased the risk of postoperative hypoxemia. The independent predictors of intraoperative RBC transfusion, such as iron deficiency and female, were identified, which may be helpful for risk assessment and perioperative management.

Fibroblast growth factor 21 (FGF21) promotes porcine granulosa cell estradiol production and proliferation via PI3K/AKT/mTOR signaling.

The proliferation and steroidogenesis of mammalian ovarian granulosa cells (GCs) are related to follicular development. Previous studies found that fibroblast growth factor 21 (FGF21) regulated female fertility through the hypothalamic-pituitary-gonad axis. However, FGF21 receptors are expressed on GCs, so we speculate that it might affect female reproduction by regulating their physiological activities. Here, we showed that FGF21, fibroblast growth factor receptor-1(FGFR1), and beta-klotho (KLB) were expressed in porcine GCs. ELISA assays showed that estradiol (E2) production was increased significantly when treating GCs with recombinant FGF21 (rFGF21). In addition, rFGF21 upregulated the mRNA and protein levels of E2 synthesis-related genes including StAR, CYP11A1, and CYP19A1 in porcine GCs. Correspondingly, FGF21 siRNA inhibited E2 levels and its synthesis-related gene expression. After rFGF21 treatment, CCK8 showed increased cell viability, and flow cytometry showed that the number of S phase increased, and cycle-related genes also increased. However, treatment with FGF21 siRNA to porcine GCs suppressed the cell cycle, viability, and EdU positive cell number. Consequently, FGF21/FGFR1/KLB forms a complex to activate the phosphatidylinositol-3-kinase (PI3K)/AKT/mTOR signaling pathway and further promote the proliferation and E2 synthesis in porcine GCs. Collectively, these findings suggests that FGF21 regulates porcine ovarian folliculogenesis.

Rational construction of a triphenylphosphine-modified tetra-nuclear Cu(I) coordinated cluster for enhanced chemodynamic therapy.

A triphenylphosphine-modified tetra-nuclear Cu(I) coordinated cluster was constructed for enhanced chemodynamic therapy (CDT) by increasing the number of metal centers. Once inside human bladder cancer (T24) cells, a larger amount of copper accumulated compared with the mono-nuclear Cu(I) complex; the additional copper could generate more •OH and then induce more obvious apoptosis via a Fenton-like reaction, thus further increasing the tumor inhibition effect and ultimately improving the CDT efficiency.

Irisin alleviates FFA induced ß-cell insulin resistance and inflammatory response through activating PI3K/AKT/FOXO1 signaling pathway.

PURPOSE: Type 2 diabetes mellitus is characterized by insulin resistance and ß-cell dysfunction. Elevated free fatty acids-induced lipotoxicity may play a vital role in the pathogenesis of ß-cell insulin resistance. Exercise-stimulated myokine irisin has been reported to be closely related to T2DM. However, its function on ß-cell insulin signaling and the underlying mechanisms are only partially elucidated as yet. METHODS: High-fat diet-fed C57BL/6J mice and palmitic acid-treated MIN6 cell models were utilized as lipotoxic models. Factors associated with ß-cell insulin signaling transduction and inflammatory responses were assessed in these models. Furthermore, the role of irisin in ß-cells and the underlying mechanisms were also explored. RESULTS: Irisin effectively decreased lipid levels in HFD mice, enhanced glucose-stimulated insulin secretion and nullified the expressions of inflammatory cytokines in vivo and in vitro experiments. Moreover, irisin improved PI3K/AKT insulin signaling pathway and inhibited TLR4/NF-κB inflammatory signaling pathway in both islets of HFD mice and PA-treated MIN6 cells. Mechanistic analysis indicated that FOXO1 might serve as a bridge between the two pathways. CONCLUSION: Irisin alleviates lipotoxicity-induced ß-cell insulin resistance and inflammatory response through the activation of PI3K/AKT/FOXO1 signaling pathways and the inhibition of TLR4/NF-κB signaling pathways. Irisin might provide a novel therapeutic strategy for T2DM.

Genome evolution of the psammophyte Pugionium for desert adaptation and further speciation.

Deserts exert strong selection pressures on plants, but the underlying genomic drivers of ecological adaptation and subsequent speciation remain largely unknown. Here, we generated de novo genome assemblies and conducted population genomic analyses of the psammophytic genus Pugionium (Brassicaceae). Our results indicated that this bispecific genus had undergone an allopolyploid event, and the two parental genomes were derived from two ancestral lineages with different chromosome numbers and structures. The postpolyploid expansion of gene families related to abiotic stress responses and lignin biosynthesis facilitated environmental adaptations of the genus to desert habitats. Population genomic analyses of both species further revealed their recent divergence with continuous gene flow, and the most divergent regions were found to be centered on three highly structurally reshuffled chromosomes. Genes under selection in these regions, which were mainly located in one of the two subgenomes, contributed greatly to the interspecific divergence in microhabitat adaptation.

The salutary effect of peritoneal dialysis catheters on enhanced recovery among high-risk pediatric patients undergoing the left coronary transfer procedure: a cohort study.

BACKGROUND: Evidence for peritoneal dialysis catheter (PDC) usage in pediatric patients undergoing surgery for deteriorating cardiac dysfunction is lacking. This investigation explored factors associated with PDC usage and its effectiveness in children with anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). METHODS: Eighty-four children undergoing left coronary artery transfer were retrospectively recruited. The primary endpoint was the postoperative ratio of the general ward/[intensive care unit (ICU)] length of stay. Univariable and multivariable analyses were fitted to assess factors related most strongly to PDC and the ratio of general ward/ICU length of stay. RESULTS: Of the 84 patients, 17 (20.2%) underwent postoperative PDC placement. Patients with extreme cardiac dysfunction [left ventricular ejection fraction (LVEF) ≤25%] were much more likely to require a PDC (OR, 9.88; 95% CI, 2.13-45.76; P = 0.003). Moreover, univariate analysis indicated that concomitant mitral repair significantly decreased the likelihood of PDC placement (OR, 0.25; 95% CI, 0.07-0.85; P = 0.026). In those with cardiac dysfunction (LVEF ≤50%), PDC use was associated with a reduced ratio of ward/ICU length of stay (B, - 1.62; 95% CI, - 2.77- -0.46; P = 0.008), as was age ≤ 12 months (B, - 1.57; 95% CI, - 2.88- -0.26; P = 0.02). At the 1-year follow-up, cardiac improvement was significantly greater in patients with PDC usage than in those without it (P <  0.001), and the number of mitral recoveries was comparable between the groups (64.2% vs. 53.3%, P = 0.434). CONCLUSION: In cohorts with ALCAPA, PDC placement following surgery may be necessary for patients with extreme cardiac compromise, while concomitant mitral repair can probably reduce their usage rate. PDC is beneficial in conferring an improvement in cardiac and mitral performance. Importantly, after patients are transferred from the ICU, recovery efficiency in the general ward can be enhanced by PDC placement, and hospital discharge can therefore be achieved early, especially for patients younger than 12 months or with LVEF ≤50%.

Original Designed Uniportal-Bichannel Spinal Endoscopic System (UBiSES) for Foraminoplasty in Percutaneous Endoscopic Transforaminal Discectomy.

OBJECTIVE: The study introduced uniportal-bichannel spinal endoscopic system (UBiSES) and explored the feasibility of applying UBiSES to conduct lumbar foraminoplasty in percutaneous endoscopic transforaminal discectomy (PETD). METHODS: This is a cohort study. 36 patients confirmed as L5/S1 lumbar disc herniation (LDH) in our hospital from March, 2019 to November, 2019 were enrolled. 36 patients were divided into two groups named the UBiSES group (n = 18, male: female = 8:10) and the TESSYS group (n = 18, male: female = 10:8). The average age of the UBiSES group and the TESSYS group were 40.94 ± 12.39 years old and 39.78 ± 13.02 years old respectively. PETD via uniportal-bichannel foraminoplasty assisted by UBiSES was adopted on the UBiSES group while PETD via conventional foraminoplasty was performed on the TESSYS group. One experienced surgeon with more than 4000 cases of lumbar surgery performed PETD on all patients. The demographic data, the duration of working cannula placement (minutes), decompression time (minutes), radiation exposure time (seconds), complications, Visual Analogue Scale (VAS), Oswestry Disability Index (ODI) scores and modified MacNab criteria were recorded and analyzed. The magnetic resonance imaging (MRI) and computed tomography (CT) were conducted to evaluate the radiographic improvement. RESULTS: PETD via lumbar foraminoplasty was successfully performed in all cases. The follow-up points were 3 months, 6 months, and 12 months. The average follow-up period of all patients was 15.78 ± 2.29 months. There was no statistic difference in age (P = 0.81), sex (P = 0.51) and follow-up (P = 0.14) between two groups. The duration of working cannula placement was 19.08 ± 2.30 min in the UBiSES group and 24.90 ± 4.71 min in the TESSYS group and there was significant difference between two groups (P < 0.05). There was no statistic difference in decompression time between the UBiSES group (44.18 ± 5.70 min) and the TESSYS group (47.46 ± 5.96 min) (P = 1.70). The radiation exposure time was 28.00 ± 4.70 s in the UBiSES group and 40.50 ± 5.73 s in the TESSYS group respectively, and has significant difference between two groups (P < 0.05). Furthermore, there was significant different in the duration of working cannula placement and radiation exposure time in male or female between the UBiSES group and the TESSYS group (P < 0.05). For male or female, no difference observed in decompression time and follow-up period between two groups. Postoperative VAS of low back and leg at every follow-up point (1 day, 3 months, 6 months, 12 months) was improved significantly in both groups compared with their preoperative VAS (P < 0.05). The postoperative ODI (3 months, 6 months, 12 months) has decreased significantly in both the UBiSES group and the TESSYS group compared with their preoperative ODI (P < 0.05). 94.44% patients received an excellent or good recovery in the UBiSES group and 88.89% for the TESSYS group. There was no poor result reported in both groups. The radiographic images showed satisfactory foraminoplasty and sufficient decompression of nerve in both groups. No postoperative complications were observed during follow-ups in the UBiSES group. Two patients in the TESSYS group experienced postoperative dysesthesia and the symptom was disappeared in 5 days and 7 days respectively with dexamethasone and neurotrophic drugs treatment. CONCLUSIONS: The original designed UBiSES could effectively and safely enlarge the foramen with an extensive surgical view and space under full-time and real-time visualization and get satisfactory efficacy.

Export of RNA-derived modified nucleosides by equilibrative nucleoside transporters defines the magnitude of autophagy response and Zika virus replication.

RNA contains a wide variety of posttranscriptional modifications covalently attached to its base or sugar group. These modified nucleosides are liberated from RNA molecules as the consequence of RNA catabolism and released into extracellular space, but the molecular mechanism of extracellular transport and its pathophysiological implications have been unclear. In the present study, we discovered that RNA-derived modified nucleosides are exported to extracellular space through equilibrative nucleoside transporters 1 and 2 (ENT1 and ENT2), with ENT1 showing higher preference for modified nucleosides than ENT2. Pharmacological inhibition or genetic deletion of ENT1 and ENT2 significantly attenuated export of modified nucleosides thereby resulting in their accumulation in cytosol. Using mutagenesis strategy, we identified an amino acid residue in ENT1 that is involved in the discrimination of unmodified and modified nucleosides. In ENTs-deficient cells, the elevated levels of intracellular modified nucleosides were closely associated with an induction of autophagy response as evidenced by increased LC3-II level. Importantly, we performed a screening of modified nucleosides capable of inducing autophagy and found that 1-methylguanosine (m1G) was sufficient to induce LC3-II levels. Pathophysiologically, defective export of modified nucleosides drastically induced Zika virus replication in an autophagy-dependent manner. In addition, we also found that pharmacological inhibition of ENTs by dilazep significantly induced Zika virus replication. Collectively, our findings highlight RNA-derived modified nucleosides as important signaling modulators that activate autophagy response and indicate that defective export of these modified nucleoside can have profound consequences for pathophysiology.

Risk Factors for Prolonged Mechanical Ventilation After Pulmonary Endarterectomy: 7 Years' Experience From an Experienced Hospital in China.

Background: Prolonged mechanical ventilation (PMV) is common after cardiothoracic surgery, whereas the mechanical ventilation strategy after pulmonary endarterectomy (PEA) has not yet been reported. We aim to identify the incidence and risk factors for PMV and the relationship between PMV and short-term outcomes. Methods: We studied a retrospective cohort of 171 who undergoing PEA surgery from 2014 to 2020. Cox regression with restricted cubic splines was performed to identify the cutoff value for PMV. The Least absolute shrinkage and selection operator regression and logistic regressions were applied to identify risk factors for PMV. The impacts of PMV on the short-term outcomes were evaluated. Results: PMV was defined as the duration of mechanical ventilation exceeding 48 h. Independent risk factors for PMV included female sex (OR 2.911; 95% CI 1.303-6.501; P = 0.009), prolonged deep hypothermic circulatory arrest (DHCA) time (OR 1.027; 95% CI 1.002-1.053; P = 0.036), increased postoperative blood product use (OR 3.542; 95% CI 1.203-10.423; P = 0.022), elevated postoperative total bilirubin levels (OR 1.021; 95% CI 1.007-1.034; P = 0.002), increased preoperative pulmonary artery pressure (PAP) (OR 1.031; 95% CI 1.014-1.048; P < 0.001) and elongated postoperative right ventricular anteroposterior dimension (RVAD) (OR 1.119; 95% CI 1.026-1.221; P = 0.011). Patients with PMV had longer intensive care unit stays, higher incidences of postoperative complications, and higher in-hospital medical expenses. Conclusions: Female sex, prolonged DHCA time, increased postoperative blood product use, elevated postoperative total bilirubin levels, increased preoperative PAP, and elongated postoperative RVAD were independent risk factors for PMV. Identification of risk factors associated with PMV in patients undergoing PEA may facilitate timely diagnosis and re-intervention for some of these modifiable factors to decrease ventilation time and improve patient outcomes.