The Gender Gap in the Relationship between Metabolic Syndrome and Restrictive Ventilatory Defects.

BACKGROUND: Given the fundamental physiological differences between the sexes, this study aimed to investigate the effect of metabolic syndrome on ventilatory defects stratified by sex. METHODS: We conducted a nationwide, pooled, cross-sectional study. Data from 45,788 participants (men, n = 15,859; women, n = 29,929) aged 30 years or more were obtained from the Taiwan Biobank. Age-sex-adjusted and multivariate logistic regression models were used to estimate the risk of developing impaired pulmonary function (restrictive or obstructive ventilatory defects) in individuals with or without metabolic syndromes. Separate models were also used to estimate the effect of metabolic syndrome scores and the effect of individual metabolic abnormalities on the risk of restrictive ventilatory defects. RESULTS: The overall prevalence of metabolic syndrome was estimated to be 15.9% in Taiwan, much higher in men than in women (18.6% versus 14.4%). A significant association was observed between metabolic syndromes and the risk of restrictive ventilatory defects. The risk of developing a restrictive ventilator defect was 35% higher in participants with metabolic syndromes (odds ratio, 1.35; 95% confidence interval, 1.26-1.45) than in those without metabolic syndromes. Elevated blood pressure and a triglycerides abnormality were important predictors of restrictive ventilator defects. Sex-stratified subgroup analyses of the individual metabolic abnormalities indicated that men with abdominal obesity and women with dysglycemia were more likely to develop restrictive ventilatory defects. CONCLUSIONS: Our study's evidence suggested that metabolic syndromes were important predictors of impaired pulmonary function and an increased risk of developing restrictive ventilatory defects, and its risk increased with increasing numbers of metabolic abnormalities.

Performance of pharmaceutical products removal in a bioelectrochemical system at low temperatures and changes in microbial communities and antibiotic resistance genes.

Biological methods do not effectively remove pharmaceutical products (PPs) and antibiotic resistance genes (ARGs) from wastewater at low temperatures, leading to environmental pollution. Therefore, anaerobic-aerobic-coupled upflow bioelectrochemical reactors (AO-UBERs) were designed to improve the removal of PPs at low temperatures (10 ± 2 °C). The result shows that diclofenac (DIC) and ibuprofen (IBU) removals in the system with aerobic anodic and anaerobic cathodic chambers were 91.7% and 94.7%, higher than that in the control system (12.2 ± 1.5%, 36.5 ± 5.9%), and aerobic zone favors DIC and IBU removal; fluoroquinolone antibiotics (FQs) removals in the system with aerobic cathodic and anaerobic anodic chambers were 17.5-22.4% higher than that in the control system (9.1-22.4%), and anaerobic zone favors FQs removal. Analysis of microbial community structure and ARGs showed that different electrotrophic microbes (Flavobacterium, Acinetobacter, and Delftia) with cold-resistant ability to degrade PPs were enriched in different electrode combinations, and the aerobic cathodic chambers could remove certain ARGs. These results showed that AO-UBERs under intermittent electrical stimulation mode are an alternative method for the effective removal of PPs and ARGs at low temperatures.

Efficacy and safety of VEGFR inhibitors for recurrent ovarian cancer: a systematic review.

Aim: Vascular endothelial growth factor receptor inhibitors (VEGFRIs) have been common used for recurrent ovarian cancer (ROC), but insufficient high-level evidence on verifying its efficacy and safety. Methods: Randomized controlled trials (RCTs) were searched under eight electronic databases. Stata 14.0 and Review Manager 5.3 were used for data analysis. Certainty of the evidence was assessed using the GRADE profiler. This systematic review (SR) was registered under INPLASY (INPLASY202120019). Conclusion: Totally 23 RCTs involving 2810 patients were included in this SR. Current evidence revealed that VEGFRIs had better efficacy, survival and quality of life in the treatment of ROC. Though VEGFRIs increase some drug-related adverse events (AEs), all the AEs could be manageable in the clinical practice.

The expression of VEGF/VEGF receptors (VEGFRs) in ovarian cancer (OC) tissue was found to be higher than in benign or normal ovarian tissue. Therefore angiogenesis inhibitors play an essential role in OC treatment. Many anti-angiogenic agents have been developed in recent years. The role of small-molecule inhibitors of VEGFRs for recurrent OC (ROC) has demonstrated significant antitumor efficacy. These drugs include Nintedanib, Axitinib, Pazopanib, Sorafenib, Vandetanib, Sunitinib, Cediranib, Ramucirumab and Apatinib, and more are in the way. However, insufficient high-level evidence from systematic reviews (SRs) focused on VEGFRIs for ROC. Therefore, we performed an SR to investigate the efficacy and safety of VEGFRIs for patients with ROC. This SR was registered under INPLASY (INPLASY202120019). Totally 23 RCTs involving 2810 patients were included in this SR. The results indicate that VEGFRIs have better efficacy and survival in the treatment of ROC. Though VEGFRIs increase some drug-related adverse events, all the adverse events could be manageable in clinical practice.

The association of haemoglobin A1c variability with adverse outcomes in patients with atrial fibrillation prescribed anticoagulants.

AIMS: The association of haemoglobin A1c (HbA1c) variability with the risk of adverse outcomes in patients with atrial fibrillation (AF) prescribed anticoagulants remains unclear. This study aimed to evaluate the association of HbA1c variability with the risk of ischaemic stroke (IS)/systemic embolism (SE) and all-cause mortality among patients with non-valvular AF prescribed anticoagulants. METHODS AND RESULTS: Patients newly diagnosed with AF from 2013 to 2018 were included. Variability in HbA1c, indexed by the coefficient of variation (CV), was determined for those with at least three HbA1c measurements available from the time of study enrolment to the end of follow-up. To evaluate whether prevalent diabetes would modify the relationship between HbA1c variability and outcomes, participants were divided into diabetes and non-diabetes groups. The study included 8790 patients (mean age 72.7% and 48.5% female). Over a median follow-up of 5.5 years (interquartile range 5.2, 5.8), the incident rate was 3.74 per 100 person-years for IS/SE and 4.89 for all-cause mortality in the diabetes group. The corresponding incident rates in the non-diabetes group were 2.41 and 2.42 per 100 person-years. In the diabetes group, after adjusting for covariates including mean HbA1c, greater HbA1c variability was significantly associated with increased risk of IS/SE [hazard ratio (HR) = 1.65, 95% confidence interval (CI): 1.27-2.13) and all-cause mortality (HR = 1.24, 95% CI: 1.05-1.47) compared with the lowest CV tertile. A similar pattern was evident in the non-diabetes group (IS/SE: HR = 1.58, 95% CI: 1.23-2.02; all-cause mortality: HR = 1.35, 95% CI: 1.10-1.64). CONCLUSION: Greater HbA1c variability was independently associated with increased risk of IS/SE and all-cause mortality among patients with AF, regardless of diabetic status.

In patients with atrial fibrillation (AF), greater haemoglobin A1c (HbA1c) variability was independently associated with increased risk of ischaemic stroke/systemic embolism and all-cause mortality, regardless of diabetic status. The usefulness of HbA1c variability as a risk predictor is significant and could be integrated into the stratification of patients with AF. Even if HbA1c measurements are within standard guideline limits, patients with larger fluctuations in HbA1c level may be at higher risk of thromboembolism and death than patients with more stable HbA1c level.

Molecular characteristics of patients with colorectal signet-ring cell carcinoma with different ABO blood groups.

Background: Colorectal signet-ring cell carcinoma (SRCC) is a rare subtype of malignant adenocarcinoma, accounting for approximately 1 % of colorectal cancer (CRC) cases. Its biomarkers and molecular characteristics remain controversial, and there are no specific therapeutic targets or strategies for its clinical treatment. Methods: A retrospective study was conducted between January 2010 and December 2021. 1058 colorectal cancer cases from the Sun Yat-sen University Cancer Center and 489 cases from the Tumor Genome Atlas Project were included in the analysis, of which 64 were SRCC. Data extraction included patient demographics, blood types and risk factors, including clinical variables and genomics (either a 19-gene panel NGS or 1021-gene panel NGS). Univariate analyses were performed to identify factors significantly associated with overall survival. Results: The blood groups of 27 (42.2 %), 18 (28.1 %), 12 (18.8 %), and seven (10.9 %) patients were classified as O, A, B, and AB, respectively. We found that O was a unique blood group characterized by a low frequency of KRAS mutations, a high frequency of heterozygosity at each HLA class I locus, and a high tumor mutational burden (TMB). Patients in blood group A with high-frequency KRAS mutations and those in blood group B with anemia and metabolic abnormalities required targeted treatment. Furthermore, genetic alterations in SRCC differed from those in adenocarcinoma and mucinous adenocarcinoma. Conclusions: Our study revealed genomic changes in SRCC patients across different blood groups, which could advance the understanding and precise treatment of colorectal SRCC.

Genetic and clinical characteristics of catecholaminergic polymorphic ventricular tachycardia in a Taiwanese nationwide cohort.

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare and lethal arrhythmia. Ryanodine receptor 2 (RYR2) mutation accounts for ∼60% of CPVT patients which is inherited in an autosomal dominant pattern. OBJECTIVE: This study aimed to identify CPVT-related mutations and clinical characteristics among Taiwanese CPVT patients and compare to other cohorts worldwide. METHODS: Clinical and genetic data were obtained from the Sudden Arrhythmia Death Syndrome Registry in Taiwan (SADS-TW). Forty clinically diagnosed Taiwanese CPVT patients were included. RESULTS: This is the first nationwide CPVT cohort in Taiwan. Among the 29 Taiwanese patients with CPVT-related gene mutations, 55% had RYR2 mutations, a rate similar to other ethnicities. Three out of 12 RYR2 variants were unreported. Exercise-induced symptoms including syncope and cardiac arrest were more frequent in East Asian cohorts (Taiwanese 79%, Japanese 91%), compared to Caucasian cohorts (59%) (p = 0.002). CONCLUSION: The discovery of diverse RYR2 mutations in the Taiwanese CVPT population demonstrates the importance of genetic testing in different ethnicities.

Epigallocatechin Gallate Derivative Y6 Reverses Oxaliplatin Resistance in Hepatocellular Carcinoma via Targeting the MiR-338-3p/HIF-1α/TWIST Axis to Inhibit EMT.

BACKGROUND: The emergence of drug resistance to oxaliplatin (OXA) is one of the critical obstacles in the therapy of advanced Hepatocellular Carcinoma (HCC). As an ethyl derivative of the natural compound epigallocatechin gallate (epigallocatechin-3-gallate, EGCG), Y6 was found to be able to enhance the sensitivity of HCC cells to doxorubicin. This study aimed to investigate the effect of Y6 on oxaliplatin resistance in HCC. METHODS: MTT was used to determine the reversal effect of Y6 on OXA resistance. To further explore the reversal mechanism, we treated OXA alone or in combination with Y6 or EGCG in drugresistant cells and observed the morphological changes of the cells. At the same time, transwell assay was used to detect the invasion and migration ability of cells. Moreover, Real-time PCR and Western blot analysis were performed to determine the expression levels of the miR-338-3p gene, HIF-1α/Twist proteins, and EMT-related proteins. RESULTS: We found that Y6 could inhibit the proliferation of HCC cells and effectively reverse the drug resistance of oxaliplatin-resistant human liver cancer cells (SMMC-7721/OXA) to OXA, and the reversal effect was more significant than that of its lead drug EGCG. Most of the cells in the control group and OXA group showed typical mesenchymal-like cell morphology, while most of the cells in co-administration groups showed typical epithelioid cell morphology, and the ability of the cells to invade and migrate decreased dramatically, particularly in Y6 plus OXA group. At the same time, Y6 could up-regulate the EMT epithelial marker protein E-cadherin and down-regulate the interstitial marker protein Vimentin. In addition, in co-administration groups, the expression of miR-338-3p was up-regulated, while the expression of HIF-1α and Twist was down-regulated. CONCLUSION: Y6 significantly enhanced the susceptibility of drug-resistant cells to OXA, and the process may be related to the regulation of miR-338-3p/HIF-1α / TWIST pathway to inhibit EMT. Therefore, Y6 could be considered an effective medication resistance reversal agent, which could improve the therapeutic effect for hepatocellular cancer patients.

Quercetin protects against hypertensive renal injury by attenuating apoptosis: an integrated approach using network pharmacology and RNA-Seq.

Quercetin is kown for its antihypertensive effects. However, its role on hypertensive renal injury has not been fully eucidated. In this study, hematoxylin and eosin staining, terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) staining, and Annexin V staining were used to assess the pathological changes and cells apoptosis in the renal tissues of Ang II-infused mice and Ang II- stimulated renal tubular epithelial cell line (NRK-52E). A variety of technologies, including network pharmacology, RNA-sequencing, immunohistochemistry, and Western blotting were performed to investigate its underlying mechanisms. Network pharmacology analysis identified multiple potential candidate targets (including TP53, Bcl-2 and Bax) and enriched signaling pathways (including apoptosis and p53 signaling pathway). Quercetin treatment significantly alleviated the pathological changes in renal tissues of Ang II-infused mice and reversed 464 differentially expressed transcripts (DETs), as well as enriched several signaling pathways, including those related apoptosis and p53 pathway. Furthermore, quercetin treatment significantly inhibited the cell apoptosis in renal tissues of Ang II-infused mice and Ang II-stimulated NRK-52E cells. Additionally, quercetin treatment inhibited the upregulation of p53, Bax, cleaved-caspase-9, and cleaved-caspase-3 protein expression and the downregulation of Bcl-2 protein expression in both renal tissue of Ang II-infused mice and Ang II-stimulated NRK-52E cells. Moreover, the molecular docking results indicated a potential binding interaction between quercetin and TP53. Quercetin treatment significantly attenuated hypertensive renal injury and cell apoptosis in renal tissues of Ang II-infused mice and Ang II-stimulated NRK-52E cells, and by targeting p53 may be one of the potential underlying mechanisms.

PI3K/AKT confers intrinsic and acquired resistance to pirtobrutinib in chronic lymphocytic leukemia.

PURPOSE: Pirtobrutinib, a non-covalent Bruton's tyrosine kinase (BTK) inhibitor, has been approved as the first agent to overcome resistance to covalent BTK inhibitors (such as ibrutinib, acalabrutinib, and zanubrutinib). However, the mechanisms of pirtobrutinib resistance in chronic lymphocytic leukemia (CLL) remain poorly understood. METHODS: To investigate pirtobrutinib resistance, we established resistant cell models using BTK knock-out via CRISPR-Cas9 or chronic exposure to pirtobrutinib in MEC-1 cells. These models mimicked intrinsic or acquired resistance, respectively. We then analyzed differential protein expression between wild-type (WT) and resistant MEC-1 cells using Revers Phase Protein microArray (RPPA) and confirmed the findings through Western Blot. Additionally, we evaluated potential drugs to overcome pirtobrutinib resistance by conducting cell proliferation assays, apoptosis studies, and animal experiments using both sensitive and resistant cells. RESULTS: MEC-1 cells developed resistance to pirtobrutinib either through BTK knock-out or prolonged drug exposure over three months. RPPA analysis revealed significant activation of proteins related to the PI3K/AKT pathway, including AKT and S6, in the resistant cells. Western Blot confirmed increased phosphorylation of AKT and S6 in pirtobrutinib-resistant MEC-1 cells. Notably, both the PI3K inhibitor (CAL101) and the AKT inhibitor (MK2206) effectively reduced cell proliferation and induced apoptosis in the resistant cells. The anti-tumor efficacy of these drugs was mediated by inhibiting the PI3K/AKT pathway. In vivo animal studies further supported the potential of targeting PI3K/AKT to overcome both intrinsic and acquired resistance to pirtobrutinib. CONCLUSION: The PI3K/AKT pathway plays a crucial role in both intrinsic and acquired resistance to pirtobrutinib in CLL. Therapeutically targeting this pathway may offer a promising strategy to overcome pirtobrutinib resistance.

Training students to serve as standardized patients in an objective structured clinical examination is feasible: A mixed-methods study.

AIM: This study aimed to evaluate examinees' perceptions of the performance of student standardized patients (SPs) and to explore student SPs' experiences. BACKGROUND: Objective structured clinical examination (OSCE) is a standard approach to the task of evaluating students' clinical competency that relies on SPs. However, professional SPs are characterized by high costs and insufficient availability. Training students to serve as SPs can help address this lack of OSCE resources. However, only preliminary evidence regarding this process and its feasibility has been reported. DESIGN: We used a concurrent mixed-method study design that included quantitative surveys and qualitative group interviews. METHODS: Our sample consisted of two-year Bachelor of Nursing program students and trained student SPs who were recruited in May 2021. We used a 5-item performance evaluation tool to assess the SPs' performance. The reliability of this evaluation tool was indicated by a Cronbach's α coefficient of.95. Descriptive statistics were used to assess the examinees' satisfaction with the student SPs' performance using SPSS 28.0 software. We used a semi-structured interview guide during a group interview; the interview was transcribed verbatim and analyzed via thematic analysis with the assistance of Microsoft Word software. RESULTS: Eighty-two nursing school students responded to the survey and 10 student SPs were included in a group interview. Nursing school students rated SPs' performance favorably. The mean score assigned to the SPs on the performance scale was 4.41 out of 5. The student SPs described the challenges and benefits that they experienced regarding their role. The challenges they described included 1) staying true to my role, 2) overcoming a physically overwhelming role and 3) facing the threat of insecurity. However, the corresponding benefits included 1) gaining rewards, 2) advancing nursing competency and 3) experiencing a sense of accomplishment. CONCLUSION: After undergoing training, the SPs performed well. They experienced a variety of challenges and obtained certain benefits. In health care education, recruiting students to serve as SPs is feasible.

Construction of multifunctional interface engineering on Cu-SSZ-13@Ce-MnOx/Mesoporous-silica catalyst for boosting activity, SO2 tolerance and hydrothermal stability.

Although small pore Cu-SSZ-13 catalysts have been successful as commercial catalysts for controlling NOx emissions from mobile sources, the challenges of high light-off temperature, SO2 tolerance and hydrothermal stability still need to be addressed. Here, we synthesized a multifunctional core-shell catalyst with Cu-SSZ-13 as the core phase and Ce-MnOx supported Mesoporous-silica (Meso-SiO2) as the shell phase via self-assembly and impregnation. The core-shell catalyst exhibited excellent low-temperature activity, SO2 tolerance and hydrothermal stability compared to the Cu-SSZ-13. The Ce-MnOx species dispersed in the shell are found to enhance both the acidic and oxidative properties of the core-shell catalyst. More critically, these species can rapidly activate NO and oxidize it to NO2, which allows the NH3-SCR reaction on the core-shell catalyst to be initiated in the shell phase. Meanwhile, Ce-MnOx species can react preferentially with SO2 as sacrifice components, effectively avoiding the sulfur inactivation of the copper active sites. Furthermore, the hydrophobic Meso-SiO2 shell provides an important barrier for the core phase, which reduces the loss of active species, acid sites and framework Al of the aged core-shell catalyst and mitigates the collapse of the zeolite framework. This work provides a new strategy for the design of novel and efficient NH3-SCR catalysts.

The Structures and Compositions Design of the Hollow Micro-Nano-Structured Metal Oxides for Environmental Catalysis.

In recent decades, with the rapid development of the inorganic synthesis and the increasing discharge of pollutants in the process of industrialization, hollow-structured metal oxides (HSMOs) have taken on a striking role in the field of environmental catalysis. This is all due to their unique structural characteristics compared to solid nanoparticles, such as high loading capacity, superior pore permeability, high specific surface area, abundant inner void space, and low density. Although the HSMOs with different morphologies have been reviewed and prospected in the aspect of synthesis strategies and potential applications, there has been no systematic review focusing on the structures and compositions design of HSMOs in the field of environmental catalysis so far. Therefore, this review will mainly focus on the component dependence and controllable structure of HSMOs in the catalytic elimination of different environmental pollutants, including the automobile and stationary source emissions, volatile organic compounds, greenhouse gases, ozone-depleting substances, and other potential pollutants. Moreover, we comprehensively reviewed the applications of the catalysts with hollow structure that are mainly composed of metal oxides such as CeO2, MnOx, CuOx, Co3O4, ZrO2, ZnO, Al3O4, In2O3, NiO, and Fe3O4 in automobile and stationary source emission control, volatile organic compounds emission control, and the conversion of greenhouse gases and ozone-depleting substances. The structure-activity relationship is also briefly discussed. Finally, further challenges and development trends of HSMO catalysts in environmental catalysis are also prospected.

Combined Electrochemical Deposition and Photo-Reduction to Fabricate SERS-Active Silver Substrates: Characterization and Application for Malachite Green Detection in Aquaculture Water.

This research introduces a novel approach using silver (Ag) nanostructures generated through electrochemical deposition and photo-reduction of Ag on fluorine-doped tin oxide glass substrates (denoted as X-Ag-AgyFTO, where 'X' and 'y' represent the type of light source and number of deposited cycles, respectively) for surface-enhanced Raman spectroscopy (SERS). This study used malachite green (MG) as a Raman probe to evaluate the enhancement factors (EFs) in SERS-active substrates under varied fabrication conditions. For the substrates produced via electrochemical deposition, we determined a Raman EF of 6.15 × 104 for the Ag2FTO substrate. In photo-reduction, the impact of reductant concentration, light source, and light exposure duration were examined on X-Ag nanoparticle formation to achieve superior Raman EFs. Under optimal conditions (9.0 mM sodium citrate, 460 nm blue-LED at 10 W for 90 min), the combination of blue-LED-reduced Ag (B-Ag) and an Ag2FTO substrate (denoted as B-Ag-Ag2FTO) exhibited the best Raman EF of 2.79 × 105. This substrate enabled MG detection within a linear range of 0.1 to 1.0 µM (R2 = 0.98) and a detection limit of 0.02 µM. Additionally, the spiked recoveries in aquaculture water samples were between 90.0% and 110.0%, with relative standard deviations between 3.9% and 6.3%, indicating the substrate's potential for fungicide detection in aquaculture.

Risk factors for AKI or mortality and long-term follow-up in COVID-19 infected patients in the era nefore vaccination.

BACKGROUND: Acute kidney injury (AKI) is a severe complication of coronavirus disease 2019 (COVID-19) and is associated with a higher risk of mortality. Understanding the risk factors contributing to COVID-19-related AKI and mortality before vaccination is important for the initiation of preventative measures and early treatment strategies. METHODS: This study included patients aged ≥18 years diagnosed with COVID-19 through polymerase chain reaction from May 2020 to July 2021, admitted in three local hospitals in Taiwan, with an extended follow-up until June 30, 2022. A median follow-up period of 250 days was used to assess AKI development and mortality. AKI was defined according to the Kidney Disease Improving Global Outcomes criteria. Multivariate Cox regression analysis of AKI and mortality-related risk factors was performed. RESULTS: Of the 720 hospitalized patients with COVID-19, 90 (22%) developed AKI. Moreover, 80%, 10.1%, and 8.9% of the patients had stage 1, 2, and 3 AKI, respectively. Patients with stage 1-3 AKI had significantly lower survival rates than those without AKI (p = 0.0012). The mean duration of post-admission AKI occurrence was 9.50 ± 11.32 days. Older age, hypoalbuminemia, and higher D-dimer and ferritin levels were associated with COVID-19 mortality. In COVID-19 AKI, in addition to older age and high D-dimer and ferritin levels, chronic kidney disease emerged as an independent risk factor. CONCLUSION: COVID-19-related AKI develops early, exhibits a temporal association with respiratory failure, and is linked to an unfavorable prognosis. The mortality rate increased according to the AKI stage (p = 0.0012). Age; albumin, D-dimer, and ferritin levels; and the underlying chronic kidney disease status upon admission are crucial factors for predicting AKI development, which increases the mortality risk. Monitoring the renal function not only within 10 days of COVID-19 onset, but also within one month after the disease onset.

Multicenter registry of multisystem inflammatory syndrome in children (MIS-C) and Paired comparison with Kawasaki disease.

OBJECTIVES: This study aimed to identify clinical characteristics to differentiate multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) in Taiwan, an island with a delayed cluster of MIS-C and a high incidence of KD. Additionally, we studied risk factors for developing severe complications in patients with MIS-C. METHODS: We conducted a retrospective, multicenter, cohort, and observational study that linked data on patients with MIS-C between May and December 2022 and patients with KD between 2019 and 2021 from 12 medical centers. Hemodynamic compromise, defined as the need for inotropic support or fluid challenge, was recorded in patients with MIS-C. We also evaluated maximal coronary Z-scores before treatment and one month after disease onset. RESULTS: A total of 83 patients with MIS-C and 466 patients with KD were recruited. A 1:1 age and gender-matched comparison of 68 MIS-C and KD pairs showed that MIS-C patients had a lower percentage of positive BCG red halos, lower leukocyte/platelet counts, more gastrointestinal symptoms, and a higher risk of hemodynamic compromise. In Taiwan, 38.6% of MIS-C patients experienced hemodynamic compromise, with presence of conjunctivitis and elevated levels of procalcitonin (>1.62 ng/mL) identified as independent risk factors. CONCLUSIONS: We identified two independent risk factors associated with hemodynamic compromise in MIS-C patients. The comparison between matched MIS-C and KD patients highlighted significant differences in clinical presentations, like BCG red halos, which may aid in the differential diagnosis of the two disease entities, especially in regions with a high incidence rate of KD.

[Two new pinophol derivatives from endophytic fungus Penicillium herquei JX4 hosted in Ceriops tagal].

An OSMAC strategy was used to study secondary metabolites and anti-inflammatory activities of the endophytic fungus Penicillium herquei JX4 hosted in Ceriops tagal. The PDB ferment of fungus P. herquei JX4 was isolated, purified, and identified by using silica gel column chromatography, gel column chromatography, octadecylsilyl(ODS) column chromatography, and semi-preparative high-performance liquid chromatography. Two new pinophol derivatives, pinophol H(1) and pinophol I(2) were isolated and identified, and they were evaluated in terms of the inhibitory activities against the nitric oxide(NO) production induced by lipopolysaccharide(LPS) in mouse macrophage RAW264.7 cells. The results showed that compound 1 had significant inhibitory activity on NO production, with an IC_(50) value of 8.12 µmol·L~(-1).

Atrial flutter/fibrillation in adult congenital heart disease: Insights from a large Asian cohort.

BACKGROUND: The incidence of atrial fibrillation/atrial flutter (AF/AFL) in general population is lower in Asia compared to Western countries. It is unclear whether a similar trend exists among adults with congenital heart disease (ACHD). We determine the profile, risk factors, and impact of AF/AFL in an Asian ACHD cohort. METHODS: We included all ACHD patients diagnosed in an Asia tertiary care center between 2007 and 2018, analyzing AF (sustained and paroxysmal AF) and AFL, collectively./Purpose. RESULTS: The study encompassed 4391 patients (55.9% women), with 81% having simple, 16.3% moderate and 2.8% severe CHD. AF/AFL was observed in 6.7% of the patients, with 54.6% having paroxysmal AF, 27.3% sustained AF, and 18.1% AFL. Incidence of AF/AFL increased with age and was higher in patients with pulmonary hypertension (PH), severe CHD, and metabolic syndrome. We found a progressive trend in the onset age of arrhythmia: AFL at a younger age, followed by paroxysmal and sustained AF. Risk factors for AF/AFL included severe and moderate CHD, PH, previous interventions, and male sex (odds ratio 11.2 and 3.15, 2.03, 1.75, and 1.71, respectively). When stratifying by CHD severity, PH and male sex were significant risk factors in simple CHD, while only PH in severe CHD. Patients with AF/AFL had a significantly lower major adverse cardiovascular events-free survival rate. CONCLUSIONS: This large ACHD cohort from Asia exhibited a high incidence of AF/AFL, similar to Western reports. The risk of AF/AFL was primarily associated with hemodynamic factors such as PH and CHD severity.

Mechanism of Lian Hua Qing Wen capsules regulates the inflammatory response caused by M1 macrophage based on cellular experiments and computer simulations.

PURPOSE: The polarization of macrophages with the resulting inflammatory response play a crucial part in tissue and organ damage due to inflammatory. Study has proved Lian Hua Qing Wen capsules (LHQW) can reduce activation of inflammatory response and damage of tissue derived from the inflammatory reactions. However, the mechanism of LHQW regulates the macrophage-induced inflammatory response is unclear. Therefore, we investigated the mechanism of LHQW regulated the inflammatory response of M1 macrophages by cellular experiments and computer simulations. METHODS: This study has analysed the targets and mechanisms of macrophage regulating inflammatory response at gene and protein levels through bioinformatics. The monomeric components of LHQW were analyzed by High Performance Liquid Chromatography (HPLC). We established the in vitro cell model by M1 macrophages (Induction of THP-1 cells into M1 macrophages). RT-qPCR and immunofluorescence were used to detect changes in gene and protein levels of key targets after LHQW treatment. Computer simulations were utilized to verify the binding stability of monomeric components and protein targets. RESULTS: Macrophages had 140,690 gene targets, inflammatory response had 12,192 gene targets, intersection gene targets were 11,772. Key monomeric components (including: Pinocembrin, Fargesone-A, Nodakenin and Bowdichione) of LHQW were screened by HPLC. The results of cellular experiments indicated that LHQW could significantly reduce the mRNA expression of CCR5, CSF2, IFNG and TNF, thereby alleviating the inflammatory response caused by M1 macrophage. The computer simulations further validated the binding stability and conformation of key monomeric components and key protein targets, and IFNG/Nodakenin was able to form the most stable binding conformation for its action. CONCLUSION: In this study, the mechanism of LHQW inhibits the polarization of macrophages and the resulting inflammatory response was investigated by computer simulations and cellular experiments. We found that LHQW may not only reduce cell damage and death by acting on TNF and CCR5, but also inhibit the immune recognition process and inflammatory response by regulating CSF2 and IFNG to prevent polarization of macrophages. Therefore, these results suggested that LHQW may act through multiple targets to inhibit the polarization of macrophages and the resulting inflammatory response.