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The IL-6R/JAK2/STAT3 pathway mediated by interleukin-6 (IL-6) plays an important role in the occurrence and development of multiple myeloma (MM), which is associated with decreased microRNA-451a. However, the biological function of microRNA-451a in MM remains unclear. The bone marrow (BM) of patients with MM was sampled, and the plasma cells were enriched. BM miR-451a, IL-6 and IL-6R levels and Ki-67 expression intensity were evaluated using reverse transcription-quantitative PCR, ELISA and flow cytometry, respectively. U266 cell proliferation, viability and apoptosis were measured using BrdU, CCK-8 and Annexin V/propidium iodide assays, respectively. Total and phospo-(p-)JAK2 and p-STAT3 levels were measured by western blotting. Dual-luciferase reporter assays were performed to validate the predicted target binding sites. miR-451a expression was low in patients with MM and was associated with the Revised International Staging System (R-ISS) stage. IL-6 concentrations were significantly higher in patients with MM than in normal controls and were inversely associated with miR-451a levels (r=−0.96, P<0.0001). IL-6R levels were positively correlated with the R-ISS stage. miR-451a was downregulated, and IL-6R was upregulated in myeloma cell lines. Treatment with an miR-451a mimic inhibited viability and induced apoptosis in U266 cells. p-JAK2 and p-STAT3 levels were significantly lower in mimic-treated U266 cells than in control cells. Thus, miR-451a was shown to regulate myeloma cell proliferation and apoptosis via the IL-6R/JAK2/STAT3 pathway and may be used to predict patient prognosis.

The natural course of multiple myeloma (MM) varies greatly between patients. The Revised MM International Staging System (R-ISS) identifies high-risk patients, but it is unsuitable for assessing minimal residual disease (MRD). Furthermore, the focal location of myeloma cells and clonal evolution often produce false negative results in flow cytometry. Extracellular microRNA (miRNA/miR) expression levels are stable in bodily fluids, and are retrievable and measurable from fresh or archived serum or plasma samples. Therefore, the present study aimed to investigate the clinical utility of circulating miRNA levels in patients with MM, particularly miR-451a, which is commonly downregulated in MM, and whether it could predict the prognosis and relapse of patients with MM. In total, 66 patients with MM, stratified using the R-ISS criteria, were recruited, while 10 healthy subjects (transplantation donors) were enrolled as controls. Reverse transcription-quantitative PCR was used to evaluate miR-451a expression in bone marrow (BM) and in the circulation. IL-6 levels were measured using ELISA, while western blotting was conducted to analyze the protein expression levels of the IL-6 receptor (IL-6R). During follow-up, MRD was assessed via multiparameter flow cytometry (MFC). miR-451a was identified to target IL-6R using a dual-luciferase reporter assay. Circulating miR-451a levels were low in patients with MM, and was found to be 0.39 times that of the control group (U=4.00; P<0.001). Among the 66 patients with MM, the median level of miR-451a was 0.73 and 0.41 times that of the control group in R-ISS stage I MM (15 patients) and R-ISS stage II stage (17 patients), respectively; patients with R-ISS stage III MM (34 patients) had the lowest level, at 0.24 times the value of the control group. Circulating miR-451a levels had a strong positive correlation with miR-451a levels in BM, but negatively correlated with IL-6 and IL-6R levels. After two courses of consolidation chemotherapy, 19 patients achieved complete remission, 10 of whom presented steady circulating miR-451a levels during follow-up; the other nine patients had an abrupt decrease in circulating miR-451a levels. The turning points in the trend appeared 4-8 weeks before positive results were obtained via MFC, and 4-16 weeks before clinical relapse. Moreover, miR-451a overexpression notably downregulated the expression of the IL-6R mRNA and protein. Collectively, circulating miR-451a levels potentially represent a novel biomarker to monitor MRD and predict relapse.

Background To explore how emotional-modulated inhibitory control, as assessed by the emotional Go/No-Go task and EEG, correlates with the multidimensional profile of borderline personality disorder (BPD). Methods Eighty-two participants completed the Personality Assessment Inventory-Borderline Features (PAI-BOR), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7) scale. EEG was recorded during an emotional Go/No-Go task and event-related potential (ERP) components were analyzed for correlations with BPD features. Participants were then divided into groups with or without BPD features, and comparisons of ERP components were then made within groups. Results ERP analysis revealed BPD features correlations with brain activity. Affective instability was positively correlated with left frontal N2 during positive-neutral No-Go trials. Self-harm was associated with left frontal late positive potential(LPP) during negative-neutral Go trials. Left frontal and central LPP slightly related to identity problems. 32 participants grouped into participants with BPD features(the BPF group) showed more depression, anxiety, emotional instability, identity issues, self-harm, and interpersonal problems. The BPF group had impaired performance on No-Go trials, smaller N2 amplitudes at left frontal channels during negative emotional cues, and delayed N2 peak latency. A group-trial type interaction was observed, with higher LPP amplitudes in Go trials for the control group but not in the BPF group, indicating distinct emotion processing between the BPF and control groups. Conclusion The findings of this study propose that there are neural associations among affective instability, self-harm, and identity problems in BPD, which are consistent with the neural foundation of emotion-modulated inhibitory control observed in the emotional Go/No-Go task. The lack of association between negative sociality and ERP components highlights the complex nature of social information processing in BPD. Moreover, significant emotional, cognitive, and neural differences are also observed between the BPF and control groups. These results enhance understanding of how emotional valence modulates inhibitory control processes in individuals with varying levels of BPF.

Abstract Context The significance of an early diagnosis of gestational diabetes mellitus (GDM) with oral glucose tolerance test (OGTT) has not been determined. Objective The objective of this work is to investigate GDM diagnosed by early and standard OGTTs and determine adverse maternal and neonatal outcomes associated with early GDM diagnosis. Research Design and Methods The Early Diagnosis of Gestational Diabetes Mellitus study is a prospective cohort study. Each participant in the study underwent 2 OGTTs, an early OGTT at 18 to 20 gestational weeks (gws) and a standard OGTT at 24 to 28 gws. The reproduciblity between early and standard OGTT were analyzed. Maternal and neonatal metabolic disorders and pregnancy outcomes were compared across groups. Results A total of 522 participants completed both the early and standard OGTTs. The glucose values in the early OGTT were not significantly different from those in the standard OGTT (fasting: 4.31 ± 0.41 mmol/L vs 4.29 ± 0.37 mmol/L, P = .360; 1-hour: 7.68 ± 1.71 mmol/L vs 7.66 ± 1.59 mmol/L, P = .826; 2-hour: 6.69 ± 1.47 mmol/L vs 6.71 ± 1.39 mmol/L, P = .800). The reproducibility of early and standard OGTT results was 74.9%. Pregnant women in the GDM group had higher glycated hemoglobin, C-peptide, and homeostasis model assessment of insulin resistance in the late gestational period. Neonates born to mothers in the GDM group were at a higher risk of being large for gestational age (odds ratio [OR]: 3.665; 95% CI, 1.006-11.91) and were also more prone to neonatal hyperinsulinemia (OR: 3.652; 95% CI, 1.152-10.533). Conclusion Early-onset GDM diagnosed by OGTT at 18 to 20 gws is associated with maternal and neonatal metabolic disorders and adverse pregnancy outcomes. Further randomized controlled trials on the therapeutic efficacy for early-onset GDM will confirm the significance of early screening for GDM.

The safety and clinical effectiveness of extracranial-intracranial (EC-IC) bypass surgery in elderly patients with atherosclerotic internal carotid artery and/or middle cerebral artery steno-occlusive (ACMSO) disease remain ambiguous. Here, we analyzed our experience of EC-IC bypass surgery to evaluate its clinical safety and effect on the cognitive function for elderly patients with ACMSO. This retrospective study enrolled patients >60 years of age diagnosed with ACMSO who underwent EC-IC bypass surgery at the authors' center between January 2018 and January 2021. Indications for bypass surgery included symptomatic ACMSO defined by cerebral angiography and evidence of relative hypoperfusion in the territories of steno-occlusive arteries based on computed tomography perfusion (CTP) neuroimaging. All patients underwent the Montreal Cognitive Assessment preoperatively and 2 years after bypass surgery. Clinical data, such as the National Institute of Health Stroke Scale and cognitive function scores, and CTP parameters were retrospectively analyzed. The study cohort ultimately included data from 65 patients (60-68 years of age; median age, 66 years) who underwent 82 bypass surgeries. The patency rate of bridge arteries was 100% on intraoperative fluoroscopy and 95.0% (76/80) according to cerebral angiography at the last follow-up. The perioperative stroke rate was 1.54 % and the mortality rate was 3.08% in the 2nd year of follow-up. Compared with preoperative data, the mismatch volume of CTP was reduced ( < 0.001), and the Montreal Cognitive Assessment score significantly increased ( < 0.001) 2 years after bypass surgery. Forty patients in the cognitive improvement group had a higher educational level ( = 0.020), shorter course of disease ( = 0.041), shorter mean transit time (MTT) ( < 0.001), and shorter time to peak value ( = 0.015) on CTP, as determined by single-factor analysis before bypass, compared with those in the inactive group. Based on multivariate logistic regression analysis, a shorter preoperative MTT was an independent clinical factor for cognitive improvement after bypass (odds ratio 0.452 [95% confidence interval 0.082-0.760]; = 0.003). EC-IC bypass surgery was safe and improved cognitive function in elderly patients diagnosed with ACMSO. Reversible cerebral perfusion function is one of the better prognoses, which needs to be confirmed in future study.

Abstract Background Suicide has profound effects on individuals, families, and societies globally, underscoring the urgent need for effective early detection and prevention strategies. This systematic review aims to investigate the use of event-related potentials (ERPs) as a tool for identifying and monitoring suicide risk. Methods A comprehensive literature search was conducted, resulting in the inclusion of 23 articles that met the eligibility criteria. The review synthesized findings related to various ERP components associated with suicide risk. Results The analysis revealed that individuals with a history of suicide risk exhibited significantly reduced P3 amplitudes in response to novel stimuli during the go/no-go paradigm compared to healthy controls [standardized mean difference (SMD) = −0.53, 95% confidence interval (CI) = [−0.96; −0.10]]. Additionally, altered P3 responses to positive feedback on rewards indicated impairments in those at risk (SMD = −1.12, 95% CI = [−1.74; −0.49]). Variability in other ERP components was also highlighted, with several moderators, such as sample characteristics and methodological design, influencing ERP components. Conclusion The findings suggest that specific ERP components, particularly the P3, may serve as valuable indicators for assessing suicide risk. The review emphasizes the need for future research to utilize larger, more homogeneous samples and advanced analytical techniques to enhance detection accuracy. The application of ERPs is posited as a promising avenue for improving understanding of the neurocognitive mechanisms associated with suicide risk and enhancing prevention efforts.

DC power grid has the advantages of large power supply capacity, easy access to clean energy, low loss, and easy power control. With the increasing penetration rate of distributed generation and DC load in low-voltage transmission network, the traditional radial AC distribution form develops into AC-DC hybrid form. Large-scale distributed energy access is an important feature of future distribution system. Aiming at the AC-DC hybrid distribution system with soft tie-in switch and voltage source converter, considering the network congestion caused by large-scale access of distributed energy, a two-stage congestion management mechanism is proposed. This strategy solves the congestion problem of AC/DC hybrid transmission network with the help of the power flow control ability of AC/DC transmission network’s own optimization control means and congestion management services provided by distributed energy sources. According to the experiment, the total distributed generation power of DC link is 15 MW, and the load power is 10 MW, that is, the remaining power of DC link is 5 MW, the total distributed generation power of AC link is 8 MW, and the load power is 15 MW, that is, the power shortage of AC link is 7 MW. In the first stage, the tie-in switch, SOP and VSC are coordinated and optimized, and in the second stage, the flexible adjustment ability provided by distributed energy makes up for the deficiency of the adjustment ability of direct control means in some periods of severe congestion and meets the requirements of congestion management of AC-DC hybrid transmission network under high-permeability distributed generation.

The predictive factors for the progression from gestational diabetes mellitus (GDM) to type 2 diabetes remain incompletely elucidated. Our objective was to investigate the link between serum creatinine, a proxy for skeletal muscle mass, and the development of postpartum abnormal glucose metabolism (AGM). Methods: A retrospective review of the medical records of 501 women with GDM was conducted, all of whom underwent a 75 g oral glucose tolerance test (OGTT) between 4 and 12 weeks postpartum. Women were grouped based on quartiles of serum creatinine at the first antenatal visit to estimate the association between serum creatinine and postpartum AGM incidence. Results: Compared with the highest quartile of creatinine, lower quartiles were substantially linked to an increased incidence of postpartum AGM (adjusted odds ratios 3.37 [95% CI 1.77–6.42], 2.42 [95% CI 1.29–4.51] and 2.27 [95% CI 1.23–4.18], respectively). The generalized additive model suggested a linear relationship between serum creatinine levels and the risk of postpartum AGM below 68 µmol/L of serum creatinine levels. A decrease of 2 μmol/L in serum creatinine levels was found to be associated with a 10% increase in the odds of developing postpartum AGM. Linear regression revealed that a low serum creatinine level was linked to a higher postpartum 2-h glucose level and a decreased insulinogenic index (p = 0.007 and p = 0.027, respectively). Conclusions: An association was observed between lower serum creatinine levels in early pregnancy and an increased risk of postpartum AGM and poorer β-cell function in women with a recent history of GDM. Further research is needed to understand the mechanisms underlying our findings, as well as the role of skeletal muscle mass or nutritional status in early pregnancy on later glucose metabolism.

Background Vitiligo is an acquired depigmented disorder that causes great damage to patient's appearance and mental health. Surgical treatment plays a vital role in patients with refractory vitiligo. Recipient‐site preparation (such as liquid nitrogen, mechanical dermabrasion, chemical peeling and laser) is a key step in surgical treatment. Among them, mechanical dermabrasion and CO2 laser can achieve accurate ablation in different parts and depths. Objectives To compare the advantages and disadvantages of mechanical dermabrasion and CO2 laser and their preference for different parts in cultured epithelial sheets transplantation for the treatment of vitiligo. Methods We used a self‐controlled study to compare the efficacy of mechanical dermabrasion and CO2 laser in 120 stable vitiligo patients of different parts at different time points after cultured epithelial sheets transplantation. Results No overall difference between the mechanical dermabrasion group and the CO2 laser group. While the recovery rate of different parts of the mechanical dermabrasion group was significantly different (p < 0.05). Two methods have distinct efficacy for different parts, and CO2 laser is better at treating uneven parts. Conclusions Both mechanical dermabrasion and CO2 laser have good results in cultured epithelial sheets transplantation for the treatment of vitiligo.