• McCarthy Covington posted an update 6 days, 4 hours ago

    The relevance of circular RNAs (circRNAs) has been indicated in the progression of various diseases. Nevertheless, the precise function of circRNAs in osteoarthritis (OA) remains to be established. Therefore, we aimed to investigate changes in the expression of a specific circRNA, hsa_circ_0134111 (circ_PDE1C) and predict its functions in OA. A rat model of OA was constructed to detect circ_PDE1C expression in knee joint tissues. Subsequently, CHON-001 chondrocytes were treated with IL-1β to mimic OA in vitro. circ_PDE1C was significantly overexpressed in knee cartilage tissues from OA patients relative to amputation patients. Knockdown of circ_PDE1C inhibited extracellular matrix (ECM) degradation and chondrocyte apoptosis. Furthermore, circ_PDE1C could target miR-224-5p, and miR-224-5p expressed poorly in knee cartilage tissues from OA patients. Overexpression of miR-224-5p inhibited ECM degradation and apoptosis in chondrocytes. miR-224-5p also targeted CCL2, which activated the JAK2/STAT signaling pathway, thereby promoting cartilage degradation and exacerbating the symptoms of OA patients. In conclusion, our findings underscore a novel role of circ_PDE1C in OA pathogenesis and suggest that targeting circ_PDE1C/miR-224-5p/CCL2 axis might provide an attractive approach for OA therapy.

    The aim of the present study was to assess thiol/disulfide homeostasis (TDH) parameters and ischemia-modified albumin (IMA) levels in children with Wilson Disease (WD) and to compare them to healthy controls.

    Based on the inclusion and exclusion criteria, fifteen children with WD and twenty-nine healthy children were enrolled, and serum thiol/disulfide and IMA levels were compared between groups.

    The mean values of native and total thiols were significantly lower in the WD group than in the control group. The mean value of disulfide was significantly higher in the WD group than in the control group. The mean percentages of disulfide/total thiol and native thiol/total thiol were higher in the WD group than in the control group. The IMA value was also higher in the WD group than in the control group.

    The present study demonstrating altered thiol/disulfide parameters indicates increased oxidative stress in children with WD.

    The aim of the present study was to assess thiol/disulfide homeostasis (TDH) parameters and ischemia-modified albumin (IMA) levels in children with Wilson Disease (WD) and to compare them to healthy controls. Methods Based on the inclusion and exclusion criteria, fifteen children with WD and twenty-nine healthy children were enrolled, and serum thiol/disulfide and IMA levels were compared between groups. Results The mean values of native and total thiols were significantly lower in the WD group than in the control group. The mean value of disulfide was significantly higher in the WD group than in the control group. The mean percentages of disulfide/total thiol and native thiol/total thiol were higher in the WD group than in the control group. The IMA value was also higher in the WD group than in the control group. Conclusion The present study demonstrating altered thiol/disulfide parameters indicates increased oxidative stress in children with WD.Background Different scoring systems (A2DS2, AISAPS, ISAN) have been designed to predict the risk of in-hospital stroke-associated pneumonia (SAP). Studies have assessed the accuracy of these scores for predicting SAP. We performed this meta-analysis to consolidate the evidence on the predictive accuracies for SAP of the A2DS2, AISAPS, and ISAN scores.Materials and methods We conducted a systematic search for all studies reporting the SAP predictive accuracy of A2DS2, AISAPS, or ISAN scores in the databases of PubMed Central, SCOPUS, MEDLINE, Embase, and Cochrane from inception until December 2020. We used the STATA software for the meta-analysis.Results We included 19 studies with 35 849 patients. The pooled score sensitivities were 78% (95% CI, 71%-83%) for A2DS2, 79% (95% CI, 77%-81%) for AISAPS, and 79% (95% CI, 77%-81%) for ISAN. The pooled score specificities were 73% (95% CI, 65%-80%) for A2DS2, 74% (95% CI, 69%-79%) for AISAPS, and 74% (95% CI, 69%-79%) for ISAN. We found significant heterogeneity for all the scoring systems based on the chi-square test results and an I2 statistic > 75%. We performed meta-regression to explore the source of heterogeneity and found that patient selection (p less then 0.05) and reference standards (p less then 0.05) in the sensitivity model, index test standards (p less then 0.05), flow and timing of tests (p less then 0.01) in the specificity model, and mean age (p less then 0.001) in the joint model were the source of heterogeneity.Conclusions To summarize, we found that A2S2, AISAPS and ISAN have moderate predictive accuracy for SAP with A2S2 having a stable cutoff value.Objective This study aims to develop a nomogram model to predict the survival of refractory cardiogenic shock (RCS) patients that received veno-arterial extracorporeal membrane oxygenation (VA-ECMO).Methods A total of 235 and 209 RCS patients were supported with VA-ECMO from January 2018 to December 2019 in Guangdong Provincial People’s Hospital, and from January 2020 to December 2020 in four third-grade and class-A hospitals were a development cohort (DC) and validation cohort (VC), respectively. Finally, 137 and 98 patients were included in the DC and VC. Multivariate logistic regression analysis was used to identify variables, and only these independent risk factors were used to establish the nomogram model. CCT245737 purchase The receiver operating characteristic curve (ROC), calibration plot, decision curve, and clinical impact curves were used to evaluate the nomogram’s discriminative ability, predictive accuracy, and clinical application value.Results Pre-ECMO cardiogenic arrest (pre-ECA), lactate (Lac), inotropic score (IS), and modified nutrition risk in the critically ill score (mNUTRIC score) were incorporated into the nomogram. This showed good discrimination in the DC, with an area under ROC (AUROC) and a 95% confidence interval (CI) of 0.959 (0.911-0.986). The AUROC (95% CI) of the VC was 0.928 (0.858-0.971). The calibration plots of the DC and VC presented good calibration results. The decision curve and clinical impact curve of the nomogram provided improved benefits for RCS patients.Conclusions This study established a prediction nomogram composed of pre-ECA, Lac, IS, and mNUTRIC scores that could help clinicians to predict the survival probability at hospital discharge precisely and rapidly for RCS patients that received VA-ECMO.This study investigates the effect of stent thickness and stent porosity which are important factors determining the post-treatment intra-aneurysmal hemodynamics. The study uses computational fluid dynamics (CFD) to estimate the hemodynamic behaviour flow velocity, pressure distributions, time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), besides relative residence time (RRT) blood flow distribution in a proposed stent and three other commercially available stents. The hemodynamic behaviour is compared between four different cases. In each case, each stent has the specific thickness and porosity values. The results show that the velocity magnitude inside the sac declined in thinner stents and lower porosity stents, TAWSS on the aneurysmal wall declined linearly in lower porosity stents, OSI and RRT increased obviously in thicker stents and higher porosity stents. Finally, the results conclude that the stent with the lowest thickness and porosity has the best performance that leads to post-stent thrombus formation and healing. However, the proposed stent design, a more porous construct, has a higher RRT compared to the used commercially available stents, which helps promote the thrombus growth inside the aneurysm sac.MiR-206 is abnormally expressed in infant hemangioma endothelial cells (HemECs), but the mechanism is not clear. We explored the intervention of miR-206 in HemECs in relation to extracellular matrix (ECM) metabolism. We selected 48 cases of infantile hemangioma (IH) from volunteer organizations. After the isolated and extracted HemECs were interfered with overexpressed or silenced miR-206, the effects of miR-206 on the proliferation, migration and invasion of HemECs were examined through basic cell function experiments. The expression differences of miR-206, DNA Methyltransferase 3A (DNMT3A) and ECM-related genes were analyzed as needed by qRT-PCR or Western blot. TargetScan and dual-luciferase experiments were applied to predict and confirm the binding relationship between miR-206 and DNMT3A. The correlation between miR-206 and DNMT3A was analyzed in IH tissues by Pearson correlation coefficient, and further confirmed in HemECs by conducting rescue experiments. A nude mouse model of xenograft tumor was constructed to verify the results of in vitro experiments. MiR-206, which was downregulated in proliferative hemangioma, suppressed the malignant development of HemECs by regulating ECM-related genes. As the target gene of miR-206, DNMT3A was high-expressed in IH tissues and was negatively correlated with miR-206. Overexpressed DNMT3A counteracted the inhibitory effect of miR-206 mimic on HemECs and its regulatory effect on ECM. The results of in vivo experiments were consistent with those from cell experiments. Thus, miR-206 could promote ECM accumulation through targeted inhibition of DNMT3A, further inhibiting the malignant development of HemECs and relieving IH.Purpose To investigate the clinical outcomes of methicillin-resistant Staphylococcus aureus (MRSA) endophthalmitis.Methods Clinical courses were reviewed for 17 eyes (15 patients) with endogenous MRSA endophthalmitis based on positive blood and vitreous culture or clinical suspicion between 2013 to 2019 at Duke University Hospitals.Results Of 17 eyes, initial VA ranged from 20/40 to light perception. Of 15 patients, 9 had predisposing risk factors for bacteremia. All eyes received intravitreal vancomycin, 13 also received ceftazidime, and 2 also received amikacin instead of ceftazidime. Nine eyes developed retinal detachment; 6 underwent vitrectomy. Final VA ranged from 20/20 to no light perception and was ≥20/200 in 8 eyes. Eleven eyes had improved VA, 2 eyes were unchanged, and 4 were worse.Conclusions This study is the largest series on endogenous MRSA endophthalmitis to date. Patients had a higher proportion of final VA ≥20/200, similarly high rate of RD, and fewer enucleations compared to prior reports.Purpose The meibomian glands are located in the tarsal plate of the upper and lower eyelid and are responsible for the production of a lipid-rich secretion, the meibum, which forms the outer component of the tear film. Meibomian gland dysfunction results in excessive evaporation of the tear film and is the leading cause of dry eye disease (DED). Despite the high prevalence of DED, the etiology of meibomian gland dysfunction is only basically understood. In addition, the molecular mechanisms of meibomian gland maturation and physiological function are currently the focus of research.Methods A systematic literature search was performed using the main scientific databases, including all relevant published articles up to September 2020.Results This article provides an overview of the current state of knowledge about meibomian gland stem cells, cell surface marker expression and PPARγ signaling, as well as the pathological causes of meibomian gland dysfunction.Conclusion Androgen deficiency, hyperkeratinization, PPARγ signaling and inflammatory reactions including neutrophil extracellular traps (NETs) seem to be key factors within the pathological processes of the meibomian gland.