Design of customized coronavirus receptors.

Although coronaviruses use diverse receptors, the characterization of coronaviruses with unknown receptors has been impeded by a lack of infection models1,2. Here we introduce a strategy to engineer functional customized viral receptors (CVRs). The modular design relies on building artificial receptor scaffolds comprising various modules and generating specific virus-binding domains. We identify key factors for CVRs to functionally mimic native receptors by facilitating spike proteolytic cleavage, membrane fusion, pseudovirus entry and propagation for various coronaviruses. We delineate functional SARS-CoV-2 spike receptor-binding sites for CVR design and reveal the mechanism of cell entry promoted by the N-terminal domain-targeting S2L20-CVR. We generated CVR-expressing cells for 12 representative coronaviruses from 6 subgenera, most of which lack known receptors, and show that a pan-sarbecovirus CVR supports propagation of a propagation-competent HKU3 pseudovirus and of authentic RsHuB2019A3. Using an HKU5-specific CVR, we successfully rescued wild-type and ZsGreen-HiBiT-incorporated HKU5-1 (LMH03f) and isolated a HKU5 strain from bat samples. Our study demonstrates the potential of the CVR strategy for establishing native receptor-independent infection models, providing a tool for studying viruses that lack known susceptible target cells.

Trend analysis of quality indicators in palliative home care among terminally ill cancer and non-cancer patients in Taiwan: a 6-year observational study.

PURPOSE: Palliative home care services (PHCS) have been emerging for years. However, limited data exist regarding quality indicators for pain control, unplanned hospital readmissions, and household deaths among terminal cancer and non-cancer patients receiving PHCS. METHODS: We conducted a retrospective collection and recording of data from 1242 terminally ill cancer and non-cancer patients receiving PHCS. The data were obtained from the Hospice-Palliative Clinical Database (HPCD) of Taichung Veterans General Hospital (TCVGH) for the period from 2016 to 2021. T test and chi-square test were applied for characteristics and the quality indicators among cancer and non-cancer groups. Chi-square test was used for trend analysis of the number of patients receiving PHCS and the quality indicators among cancer and non-cancer groups throughout the study period. RESULTS: A total of 1242 terminally ill cancer and non-cancer patients who had received PHCS were documented by TCVGH from the years 2016 to 2021, including 221 non-cancer patients and 1021 cancer patients having an average age of 70. The number of terminally ill cancer and non-cancer patients receiving PHCS has increased annually since 2016. Another finding was that age was a statistically significant factor impacting quality indicators. On the other hand, compared to non-cancer patients, cancer patients had a higher likelihood of receiving treatment with analgesics when needed. Their odds of needing analgesics more than three times within 4 days after PHCS enrollment were significantly elevated [OR 4.188, 95% CI (1.002, 17.51)]. CONCLUSION: The results of this 6-year observational study indicate a substantial increase in the number of terminal cancer and non-cancer patients receiving PHCS over the past decade. Furthermore, aging plays an important role in life quality of terminal cancer and non-cancer patients.

Silymarin Synergizes with Antiviral Therapy in Hepatitis B Virus-Related Liver Cirrhosis: A Propensity Score Matching Multi-Institutional Study.

Hepatitis B virus (HBV)-related liver cirrhosis (HBV-LC) presents a substantial mortality and hepatocellular carcinoma (HCC) risk. While antiviral therapy (AVT) is the standard, complete HBV clearance remains elusive and may not reduce the risk of death in patients with decompensated cirrhosis. Silymarin, a centuries-old herbal remedy, has shown promise against HBV infection and as an antifibrosis therapy. This study explores the potential of silymarin combined with AVT to reduce mortality and HCC incidence in patients with HBV-LC. This research, spanning from 2001 to 2019, entailed a multi-institutional retrospective cohort study which included 8447 HBV-LC patients all undergoing AVT. After applying inclusion and exclusion criteria, the study comprised two cohorts: a case cohort receiving silymarin alongside AVT for at least 30 days, and a control cohort on AVT alone. Propensity score matching, based on baseline parameters including HBV-DNA levels, comorbidity, and an important LC medication, namely, non-selective ß-blockers, was employed to ensure balanced groups, resulting in 319 patients in each cohort for subsequent analyses. Overall mortality was the primary outcome, with HCC occurrence as a secondary outcome. Among 319 patients in both cohorts, the case cohort exhibited significant improvements in the international normalized ratio (INR), model for end-stage liver disease (MELD) score and the Charlson comorbidity index (CCI) one year after the index date. A competing risk survival analysis demonstrated superior one-year and two-year mortality outcomes in the case cohort. However, no significant impact on one-year and two-year HCC occurrence was observed in either cohort. The combination of silymarin and AVT in HBV-LC patients demonstrated a synergistic effect, leading to decreased overall mortality and an improved comorbidity index. While the incidence of HCC remained unchanged, our results suggested promising potential for further clinical trials investigating the synergistic role of silymarin in the treatment of HBV-LC.

A survey of knowledge, attitudes, and practices among paediatric intensive care unit nurses for preventing pressure injuries: An analysis of influencing factors.

To explore the knowledge, attitudes and practice (KAP) status of preventing pressure injury among clinical nurses working in paediatric ICU, and to examine factors affecting nurses' KAP. A questionnaire survey was conducted among 1906 paediatric ICU nurses in 18 children's hospitals by convenience sampling method. The survey tools were self-designed general data questionnaire, KAP questionnaire for the prevention of pressure injury and the influencing factors were analysed. A total of 1906 valid questionnaires were collected. The scores of overall KPA, knowledge, attitudes, and practice were 101.24 ± 17.22, 20.62 ± 9.63, 54.93 ± 5.81and 25.67 ± 6.76, respectively. The results of multiple linear regression analysis showed that education background, professional title, age and specialist nurse were the main influencing factor of nurses' knowledge of preventing PI; education background and specialist nurse were the main influencing factors of nurses' attitudes of preventing PI; knowledge, attitudes and education background were the main influencing factors of nurses' practice of preventing PI. Paediatric ICU nurses have a positive attitude towards the prevention of PI, but their knowledge and practice need to be improved. According to different characteristics of nurses, nursing managers should carry out training on the knowledge of prevention of PI to establish a positive attitude, so as to drive the change of nursing practice and improve the nursing practice level of ICU nurses to prevent of PI.

2024 Update of the TSOC Expert Consensus of Fabry Disease.

As an X-linked inherited lysosomal storage disease that is caused by α-galactosidase A gene variants resulting in progressive accumulation of pathogenic glycosphingolipid (Gb3) accumulation in multiple tissues and organs, Fabry disease (FD) can be classified into classic or late-onset phenotypes. In classic phenotype patients, α-galactosidase A activity is absent or severely reduced, resulting in a more progressive disease course with multi-systemic involvement. Conversely, late-onset phenotype, often with missense variants (e.g., IVS4+919G>A) in Taiwan, may present with a more chronic clinical course with predominant cardiac involvement (cardiac subtype), as they tend to have residual enzyme activity, remaining asymptomatic or clinically silent during childhood and adolescence. In either form, cardiac hypertrophy remains the most common feature of cardiac involvement, potentially leading to myocardial fibrosis, arrhythmias, and heart failure. Diagnosis is established through α-galactosidase enzyme activity assessment or biomarker analyisis (globotriaosylsphingosine, Lyso-Gb3), advanced imaging modalities (echocardiography and cardiac magnetic resonance imaging), and genotyping to differentiate FD from other cardiomyopathy. Successful therapeutic response relies on early recognition and by disease awareness from typical features in classic phenotype and cardiac red flags in cardiac variants for timely therapeutic interventions. Recent advances in pharmacological approach including enzyme replacement therapy (agalsidase alfa or beta), oral chaperone therapy (migalastat), and substrate reduction therapy (venglustat) aim to prevent from irreversible organ damage. Genotype- and gender-based monitoring of treatment effects through biomarker (Lyso-Gb3), renal assessment, and cardiac responses using advanced imaging modalities are key steps to optimizing patient care in FD.

CircMAT2B facilitates the progression of head and neck squamous cell carcinoma via sponging miR-491-5p to trigger ASCT2-mediated glutaminolysis.

Circular RNAs (circRNAs) are well-known to exert significant roles in regulating the pathological processes, including human carcinogenesis. Currently, less is known about their exact roles in head and neck squamous cell carcinoma (HNSCC). Herein, we aimed to investigate and validate the role of a novel circRNA, circMAT2B, as well as its potential molecular mechanism in HNSCC progression. A cohort of 41 paired of HNSCC tumor tissues and adjacent normal tissues from HNSCC patients were collected. Further, we characterized circMAT2B expression patterns in HNSCC tissues and cell lines, as well as exploring its association with the prognosis of HNSCC patients. Biological functions on cell proliferation, apoptosis, migration, and invasion were assessed using Cell Counting Kit-8, EdU incorporation, TUNEL, wound healing, and transwell assays. Glutaminolysis was evaluated by measuring glutamine, glutamate, and α-ketoglutarate (α-KG) levels. The regulatory network of circMAT2B/miR-491-5p/ASCT2 axis was verified by RNA immunoprecipitation and luciferase reporter assays. Western blot was conducted to detect the level of ASCT2 and GLS1. Remarkably overexpressed circMAT2B was observed in HNSCC tissues and cell lines, of which high abundance was positively correlated with patients' poor prognosis. Silencing of circMAT2B inhibited cell proliferation, migration, and invasion, as well as glutaminolysis. miR-491-5p, interacted with ASCT2, was identified to be a downstream target of circMAT2B, thereby involving in circMAT2B-mediated biological effects. In summary, we draw a conclusion that circMAT2B could modulate the processes of cell proliferation, migration, invasion, and glutaminolysis of HNSCC cells partly via the miR-491-5p/ASCT2 axis by a molecular mechanism of competing endogenous RNA (ceRNA), implying an underlying circRNA-targeted therapy for HNSCC treatment.

Cardiovascular outcomes in patients with atrial fibrillation concomitantly treated with antiarrhythmic drugs and non-vitamin k antagonist oral anticoagulants.

AIMS: Limited data compared antiarrhythmic drugs (AADs) with concomitant non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients, hence the aim of the study. METHODS AND RESULTS: National health insurance database were retrieved during 2012-17 for study. We excluded patients not taking AADs, bradycardia, heart block, heart failure admission, mitral stenosis, prosthetic valve, incomplete demographic data, and follow-up <3 months. Outcomes were compared in Protocol 1, dronedarone vs. non-dronedarone; Protocol 2, dronedarone vs. amiodarone; and Protocol 3, dronedarone vs. propafenone. Outcomes were acute myocardial infarction (AMI), ischaemic stroke/systemic embolism, intracranial haemorrhage (ICH), major bleeding, cardiovascular death, all-cause mortality, and major adverse cardiovascular event (MACE) (including AMI, ischaemic stroke, and cardiovascular death). In Protocol 1, 2298 dronedarone users and 6984 non-dronedarone users (amiodarone = 4844; propafenone = 1914; flecainide = 75; sotalol = 61) were analysed. Dronedarone was associated with lower ICH (HR = 0.61, 95% CI = 0.38-0.99, P = 0.0436), cardiovascular death (HR = 0.24, 95% CI = 0.16-0.37, P < 0.0001), all-cause mortality (HR = 0.33, 95% CI = 0.27-0.42, P < 0.0001), and MACE (HR = 0.56, 95% CI = 0.45-0.70, P < 0.0001). In Protocol 2, 2231 dronedarone users and 6693 amiodarone users were analysed. Dronedarone was associated with significantly lower ICH (HR = 0.53, 95%=CI 0.33-0.84, P = 0.0078), cardiovascular death (HR = 0.20, 95% CI = 0.13-0.31, P < 0.0001), all-cause mortality (HR 0.27, 95% CI 0.22-0.34, P < 0.0001), and MACE (HR = 0.53, 95% CI = 0.43-0.66, P < 0.0001), compared with amiodarone. In Protocol 3, 812 dronedarone users and 2436 propafenone users were analysed. There were no differences between two drugs for primary and secondary outcomes. CONCLUSION: The use of dronedarone with NOACs was associated with cardiovascular benefits in an Asian population, compared with non-dronedarone AADs and amiodarone.

Use and impact of a novel nurse-led consultation model in a palliative care consultation service for terminally ill cancer patients in Taiwan: an 11-year observational study.

PURPOSE: The early integration of palliative care for terminally ill cancer patients improves quality of life. We have developed a new nurse-led consultation model for use in a palliative care consultation service (PCCS) to initiate early palliative care for cancer patients. METHODS: In this 11-year observational study, data were collected from the Hospice-Palliative Clinical Database (HPCD) of Taichung Veterans General Hospital (TCVGH). Terminally ill cancer patients who had received PCCS during the years 2011 to 2021 were enrolled. Trend analysis was performed in order to evaluate differences in outcomes seen within the categories of either a nurse-led consultation model or ordinary consultation model throughout the study period. Analysis included studying the duration of PCCS and DNR declaration, as well as awareness of disease by both patients and families before and after PCCS. RESULTS: In total, 6923 cancer patients with an average age of 64.1 years received PCCS from 2011 to 2021, with the average duration of PCCS being 11.1 days. Three thousand four hundred twenty-one patients (49.4%) received both a nurse consultation and doctor consultation during PCCS. Being admitted to the Department of Hematology, a longer duration of hospitalization, a DNR declaration after PCCS, and having had a PCCS consultation by a nurse only or both with a nurse and a doctor were significant determinants of a PCCS duration of more than 7 days. CONCLUSION: This 11-year observational study shows that the number of terminal cancer patients receiving a novel nurse-led consultation during PCCS has increased significantly during the past decade, while a nurse-led consultation model during PCCS was effective in improving the duration of PCCS among terminally ill cancer patients.

Prognostic Effects of Liver Fibrosis and Steatosis Determined Using Transient Elastography in Patients with Chronic Hepatitis B or C.

BACKGROUND: The prognostic effects of liver fibrosis and steatosis in patients with chronic hepatitis B or C are unclear. We investigated the prognostic effects of liver fibrosis and steatosis determined through transient elastography (TE) in patients with chronic hepatitis B or C. METHODS: This retrospective cohort study enrolled 5528 patients with chronic hepatitis B or C who received TE. Multivariate Cox regression was used to evaluate the associations between fibrosis and steatosis grades and the occurrence of hepatic-related events, cardiovascular events, and mortality. Liver stiffness measurements of ≥ 7.1, ≥ 9.5, and ≥ 12.5 kPa were considered to indicate significant fibrosis (≥ F2), advanced fibrosis (≥ F3), and cirrhosis (≥ F4), and controlled attenuation parameters of ≥ 230 and ≥ 264 dB/m were considered to indicate mild (S1) and moderate-to-severe (S2-S3) steatosis, respectively. RESULTS: During a median follow-up of 3.1 years, 489 patients died, 814 had hepatic-related events, and 209 had cardiovascular events. The incidences of these outcomes were lowest among individuals with no- or mild-fibrosis (F0-F1), and increased with fibrosis severity. The incidence of adverse outcomes was highest among patients without steatosis (S0) and lowest among those with moderate-to-severe steatosis. Adjusted models indicated that F2, F3, and F4 were independent risk factors and that moderate-to-severe steatosis was a favorable marker for hepatic-related events. Cirrhosis was an independent factor for mortality. CONCLUSIONS: According to TE, increasing fibrosis grades and absence of steatosis were associated with higher risks of hepatic-related events, whereas cirrhosis was a risk factor for mortality in patients with chronic hepatitis B or C.

WWOX Polymorphisms as Predictors of the Biochemical Recurrence of Localized Prostate Cancer after Radical Prostatectomy.

The downregulation of WW domain-containing oxidoreductase (WWOX), a tumor suppressor gene, is associated with the tumorigenesis and poor prognosis of various cancers. In this study, we investigated the associations between the polymorphisms of WWOX, clinicopathologic features of prostate cancer (PCa), and risk of postoperative biochemical recurrence (BCR). We evaluated the effects of five single-nucleotide polymorphisms (SNPs) of WWOX on the clinicopathologic features of 578 patients with PCa. The risk of postoperative BCR was 2.053-fold higher in patients carrying at least one "A" allele in WWOX rs12918952 than in those with homozygous G/G. Furthermore, patients with at least one polymorphic "T" allele in WWOX rs11545028 had an elevated (1.504-fold) risk of PCa with seminal vesicle invasion. In patients with postoperative BCR, the risks of an advanced Gleason grade and clinical metastasis were 3.317- and 5.259-fold higher in patients carrying at least one "G" allele in WWOX rs3764340 than in other patients. Our findings indicate the WWOX SNPs are significantly associated with highly aggressive pathologic features of PCa and an elevated risk of post-RP biochemical recurrence.

A Circular RNA, hsa_circ_0018180 (circPARD3), Triggers Glycolysis and Promotes Malignancy of Head and Neck Squamous Cell Carcinoma Through the miR-5194/ENO1 Axis.

Emerging evidence has demonstrated the pivotal roles of circular RNAs (circRNAs) in the modulation of malignancy and pathological progression among multiple human cancers. Glucose metabolism reprogramming is a widely identified characteristic for contributing to facilitate tumorigenesis. Nonetheless, their contributions to head and neck squamous cell carcinoma (HNSCC) cell glycolysis remain to be further elucidated. Herein, we aim to investigate the role of circRNA, hsa_circ_0018180 (also named as circPARD3) in HNSCC. Expression patterns of circPARD3 in HNSCC tissues and different cell lines were determined by qRT-PCR assay, as well as its correlation with the prognosis of survival. CCK-8, EdU incorporation, and transwell assays were carried out to assess the cell viability, proliferation, migration, and invasion, respectively. Glucose uptake and lactate production were evaluated by preforming glycolysis. Mechanistically, the circPARD3/miR-5194/ENO1 axis was verified by RNA immunoprecipitation (RIP) and luciferase reporter assays. Western blot analysis was employed to measure the epithelial-mesenchymal transition (EMT)-associated biomarkers. Upregulated circPARD3 observed in HNSCC tissues and cell lines indicated the poor prognosis of patients. Stable knockdown of circPARD3 dramatically exerted the suppressive effects on cell viability, proliferation, migration, and invasion, as well as glucose uptake and lactate production. Mechanistically, circPARD3 harbored miR-5194, serving as a miRNA sponge, thereby increasing ENO1 expression. Moreover, ENO1 evidently reversed miR-5194-mediated attenuated malignant behaviors. Collectively, our study identified an oncogenic role of circPARD3 in HNSCC through a novel machinery of circPARD3/miR-5194/ENO1 and provided a promising therapeutic target for HNSCC.

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OBJECTIVES: To study the value of serum fibroblast growth factor 23 (FGF23) in the diagnosis of hypophosphatemic rickets in children. METHODS: A total of 28 children who were diagnosed with hypophosphatemic rickets in Children's Hospital of Nanjing Medical University from January 2016 to June 2021 were included as the rickets group. Forty healthy children, matched for sex and age, who attended the Department of Child Healthcare of the hospital were included as the healthy control group. The serum level of FGF23 was compared between the two groups, and the correlations of the serum FGF23 level with clinical characteristics and laboratory test results were analyzed. The value of serum FGF23 in the diagnosis of hypophosphatemic rickets was assessed. RESULTS: The rickets group had a significantly higher serum level of FGF23 than the healthy control group (P<0.05). In the rickets group, the serum FGF23 level was positively correlated with the serum alkaline phosphatase level (rs=0.38, P<0.05) and was negatively correlated with maximum renal tubular phosphorus uptake/glomerular filtration rate (rs=-0.64, P<0.05), while it was not correlated with age, height Z-score, sex, and parathyroid hormone (P>0.05). Serum FGF23 had a sensitivity of 0.821, a specificity of 0.925, an optimal cut-off value of 55.77 pg/mL, and an area under the curve of 0.874 in the diagnosis of hypophosphatemic rickets (P<0.05). CONCLUSIONS: Serum FGF23 is of valuable in the diagnosis of hypophosphatemic rickets in children, which providing a theoretical basis for early diagnosis of this disease in clinical practice.

Risk of major bleeding associated with concomitant use of anticancer drugs and direct oral anticoagulant in patients with cancer and atrial fibrillation.

This study evaluated the risk of major bleeding associated with concomitant use of direct oral anticoagulant (DOAC) and anticancer drugs (ACDs), which share metabolic pathways, in patients with atrial fibrillation (AF) and cancer. We performed a retrospective cohort study using Taiwan's National Health Insurance database and included patients with AF and cancer who received DOAC prescriptions from 1 to 2012 to 31 December 2017. The incidence of major bleeding in person-quarters with concomitant use of DOAC and any of 15 ACDs with inhibitory or competitive effects of CYP3A4 or P-gp activity (docetaxel, vinorelbine, methotrexate, irinotecan, etoposide, doxorubicin, cyclophosphamide, imatinib, nilotinib, abiraterone, bicalutamide, tamoxifen, anastrozole, cyclosporine, tacrolimus) was compared with that in person-quarters with DOAC alone. Adjusted incidence-rate differences between DOAC use with and without concurrent ACDs were estimated using Poisson regression models weighted by the inverse probability of treatment. In 13,158 patients with AF and cancer (76.9 ± 8.9 years; male 60%), 1545 major bleeding events occurred during 90,540 DOAC-exposed person-quarters. Concurrent use of DOAC and any of 15 ACDs occurred in only 18% of patients. Compared with use of DOAC alone, concomitant use of DOAC and these ACDs was not associated with an increased risk of major bleeding. Co-medication with DOAC and ACDs with inhibitory or competitive effects on CYP3A4 or P-gp activity was not associated with a higher risk of major bleeding than DOAC alone. Our findings may provide clinicians with confidence regarding the safety of concurrent use of DOAC and ACDs in patients with AF and cancer.

Dual versus Single Antiplatelet Therapy in Medically Treated Acute Myocardial Infarction Patients with Baseline Thrombocytopenia - Insights from a Multi-Institute Cohort Study.

Background: The safety and efficacy of dual antiplatelet therapy (DAPT) in medically treated acute myocardial infarction (AMI) patients with baseline thrombocytopenia (platelet count < 150 × 103/uL) are unclear. Methods: In this multi-institute retrospective cohort study, we included 468 patients with medically treated AMI with baseline thrombocytopenia and separated them into single antiplatelet therapy (SAPT) and DAPT groups according to the discharge anti-thrombotic strategy. The primary outcome was net clinical adverse events (NACEs), defined as a composite of death, ischemic events (myocardial infarction, ischemic stroke, and transient ischemic attack), and major bleeding within 30 days. Results: There were 168 patients in the SAPT group (100 taking aspirin and 68 taking clopidogrel) and 300 in the DAPT group. A primary outcome occurred in 35 (24.11 per 100 patient-months) patients in the SAPT group and 39 (14.26 per 100 patient-months) patients in the DAPT group [adjusted hazard ratio (HR): 0.67; 95% confidence interval (CI): 0.40-1.10; p = 0.1145]. Kaplan-Meier curves showed favorable results in the DAPT group (log-rank p = 0.0243). Bleeding events occurred in 18 (10.71 per 100 patient-months) patients in the SAPT group and 18 (6.40 per 100 patient-months) patients in the DAPT group (adjusted HR: 0.66; 95% CI: 0.32-1.36; p = 0.2573). Conclusions: DAPT versus SAPT as discharge anti-thrombotic strategy in thrombocytopenic patients with medically treated AMI did not significantly improve NACEs at 30 days. However, there was a trend towards favorable outcomes in the DAPT group. These results should be interpreted carefully with respect to the relatively limited trial population and study design.

Dioscin ameliorates murine ulcerative colitis by regulating macrophage polarization.

Restoring immune balance by targeting macrophage polarization is a potentially valuable therapeutic strategy for ulcerative colitis (UC). Dioscin is a steroidal saponin with potent anti-inflammatory, immunoregulatory, and hypolipidemic effects. This study examined the protective effect of Dioscin on UC in mice and explored the underlying mechanisms. Mice were induced colitis by dextran sulfate sodium (DSS) and concurrently treated with Dioscin oral administration. RAW264.7 cells were skewed to M1 macrophage polarization by lipopolysaccharide (LPS) and interferon-γ (INF-γ) in vitro, and received Dioscin treatment. The results showed that Dioscin ameliorated colitis in mice, reduced macrophage M1 polarization, but markedly promoted M2 polarization in mice colon. Dioscin inhibited mammalian target rapamycin complex 1 (mTORC1)/hypoxia-inducible factor-1α (HIF-1α) signaling and restrained glycolysis in RAW264.7; however, it activated mammalian target rapamycin complex 2 (mTORC2)/peroxisome proliferator-activated receptor-γ (PPAR-γ) signal and facilitated fatty acid oxidation (FAO). The modulation of mTORs signaling may inhibit M1, but promote M2 polarization. Furthermore, the effect of Dioscin on M2 polarization was neutralized by the FAO inhibitor Etomoxir and the mTORC2 inhibitor JR-AB2-011. In parallel, the inhibitory effect of Dioscin on M1 polarization was mitigated by the mTORC1 agonist L-leucine. Both JR-AB2-011 and L-leucine blocked the therapeutic effect of Dioscin in mice with UC. Therefore, Dioscin ameliorated UC in mice, possibly by restraining M1, while skewing M2 polarization of macrophages. Regulation of mTORC1/HIF-1α and mTORC2/PPAR-γ signals is a possible mechanism by which Dioscin inhibited aerobic glycolysis and promoted FAO of macrophages. In summary, Dioscin protected mice against DSS-induced UC by regulating mTOR signaling, thereby adjusting macrophage metabolism and polarization.

Incidence and consequences of resuming oral anticoagulant therapy following hematuria and risks of ischemic stroke and major bleeding in patients with atrial fibrillation.

Following hematuria, it is uncertain to what extent a vitamin K antagonist (VKA) or non-VKA oral anticoagulant (NOAC) is resumed, and the risks of ischemic stroke/systemic embolism and major bleeding associated with NOAC and VKA resumption are unknown. A cohort study was conducted using electronic medical records collected from 2009 to 2017 at a multicenter healthcare provider in Taiwan. The cohort included 4155 atrial fibrillation patients receiving anticoagulant therapy with hematuria (age: 71.4 ± 11.2 years; 48.8% female). Within 90 days following hematuria, 3287 patients (79.1%) resumed oral anticoagulants including VKA (n = 1554, 37.4%) and NOACs (n = 1733, 41.7%), whereas 868 patients did not resume anticoagulant. Follow-up was initiated 90 days after the occurrence of hematuria, and time-varying multiple Cox regression analyses were used for comparisons between the resumption of NOAC and VKA. The event rates per 100 person-years in the VKA resumption and NOAC resumption groups were 3.04 and 3.28 for ischemic stroke/systemic embolism, and 2.63 and 2.92 for major bleeding, respectively. Patients resuming NOAC had similar risks of ischemic stroke/systemic embolism (hazard ratio 1.14, 95% CI 0.75-1.74) and major bleeding (hazard ratio 1.12, 95% CI 0.72-1.74) compared with those resuming VKA. Since 2011, the proportion of NOAC resumption has increased, whereas the proportions of VKA resumption and non-resumption have decreased. In conclusion, more and more patients who suffer a hematuria while on oral anticoagulant therapy resume NOAC. Patients resuming NOAC have similar risks of ischemic stroke/systemic embolism and major bleeding compared with those resuming VKA.

Exome-based preconception carrier testing for consanguineous couples in China.

OBJECTIVE: To evaluate the utility of clinical exome sequencing (ES)-based carrier screening in Chinese consanguineous couples. METHODS: Consanguineous couples were screened for autosomal recessive (AR) disorders using the clinical ES of 5000 genes associated with human diseases. RESULTS: We recruited 14 couples who elected to have sequencing. One couple was related as first cousins and 13 as second cousins. Both partners carrying the same pathogenic variant were detected in four couples. One couple was found in which one partner carried a splice variant, and the other had a missence variant of the same gene. These five couples were identified as being at risk of having a child affected by an AR disorder. CONCLUSION: Our study demonstrates that ES-based preconception screening yields a clinical value for Chinese consanguineous couples. It enables to detect at-risk couples for rare AR diseases.

Trend analysis of palliative care consultation service for terminally ill non-cancer patients in Taiwan: a 9-year observational study.

BACKGROUNDS: Early integration of palliative care for terminally ill non-cancer patients improves quality of life. However, there are scanty data on Palliative Care Consultation Service (PCCS) among non-cancer patients. METHODS: In this 9-year observational study Data were collected from the Hospice-Palliative Clinical Database (HPCD) of Taichung Veterans General Hospital (TCVGH). Terminally ill non-cancer patients with 9 categories of diagnoses who received PCCS during 2011 to 2019 were enrolled. Trend analysis was performed to evaluate differences in categories of diagnosis throughout study period, duration of PCCS, patient outcomes, DNR declaration, awareness of disease by patients and families before and after PCCS. RESULTS: In total, 536 non-cancer patients received PCCS from 2011 to 2019 with an average age of 70.7 years. The average duration of PCCS was 18.4 days. The distributions of age, gender, patient outcomes, family's awareness of disease before PCCS, and patient's awareness of disease after PCCS were significantly different among the diagnoses. Organic brain disease and Chronic kidney disease (CKD) were the most prevalent diagnoses in patients receiving PCCS in 2019. For DNR declaration, the percentage of patients signing DNR before PCCS remained high throughout the study period (92.8% in 2019). Patient outcomes varied according to the disease diagnoses. CONCLUSION: This 9-year observational study showed that the trend of PCCS among non-cancer patients had changed over the duration of the study. An increasing number of terminally ill non-cancer patients received PCCS during late life, thereby increasing the awareness of disease for both patients and families, which would tend to better prepare terminally ill patients for end-of-life as they may consider DNR consent. Early integration of PCCS into ordinary care for terminally non-cancer patients is essential for better quality of life.

Resuscitation outcomes of a wireless ECG telemonitoring system for cardiovascular ward patients experiencing in-hospital cardiac arrest.

BACKGROUND/PURPOSE: In-hospital cardiac arrest is a serious issue for hospitalized patients. The documented initial rhythm and detected medical events have been reported to influence the survival of cardiopulmonary resuscitation. This study aimed to identify the effect of continuous real-time electrocardiogram (ECG) monitoring on the prognosis of resuscitated patients in a general cardiac ward. METHODS: We conducted this retrospective study using medical records of hospitalized patients in a cardiovascular ward who experienced an in-hospital cardiac arrest and received cardiopulmonary resuscitation from February 2015 to December 2018. The patients who were considered to be at high risk of cardiac events such as ventricular arrhythmia would receive continuous ECG monitoring. A wireless ECG telemonitoring system was introduced to replace traditional bedside ECG monitors. The outcome measures were the initial success of resuscitation, 24-h survival after resuscitation, and survival to discharge. RESULTS: We enrolled 115 patients with a cardiac arrest during hospitalization, of whom 73 (63%) patients received wireless ECG telemonitoring. Patients receiving continuous ECG monitoring were associated with higher opportunities of initial success of resuscitation and 24-h survival after resuscitation (67.1% vs. 40.5%, p = 0.005; and 49.3% vs. 26.2%, p = 0.015, respectively) when comparing to the non-monitoring group; but no significant difference in survival to discharge (21.9% vs. 16.7%, p = 0.498) was observed. With adjustment of the covariates, the monitoring group was associated with a higher likelihood to reach the initial success of resuscitation (odds ratios [ORs], 3.21; 95% confidence interval [CI], 1.03-9.98). However, the effect of monitoring on 24-h survival and survival to discharge was close to null after adjusting for covariates. CONCLUSION: A wireless ECG telemonitoring system were beneficial to the initial success of resuscitation for patients at high risk of cardiovascular events suffering an in-hospital cardiac arrest; but had less impact on 24-h survival and survival to discharge.

2021 TSOC Expert Consensus on the Clinical Features, Diagnosis, and Clinical Management of Cardiac Manifestations of Fabry Disease.

Fabry disease (FD) is an X-linked, rare inherited lysosomal storage disease caused by α-galactosidase A gene variants resulting in deficient or undetectable α-galactosidase A enzyme activity. Progressive accumulation of pathogenic globotriaosylceramide and its deacylated form globotriaosylsphingosine in multiple cell types and organs is proposed as main pathophysiology of FD, with elicited pro-inflammatory cascade as alternative key pathological process. The clinical manifestations may present with either early onset and multisystemic involvement (cutaneous, neurological, nephrological and the cardiovascular system) with a progressive disease nature in classic phenotype, or present with a later-onset course with predominant cardiac involvement (non-classical or cardiac variant; e.g. IVS4+919G>A in Taiwan) from missense variants. In either form, cardiac involvement is featured by progressive cardiac hypertrophy, myocardial fibrosis, various arrhythmias, and heart failure known as Fabry cardiomyopathy with potential risk of sudden cardiac death. Several plasma biomarkers and advances in imaging modalities along with novel parameters, cardiac magnetic resonance (CMR: native T1/T2 mapping) for myocardial tissue characterization or echocardiographic deformations, have shown promising performance in differentiating from other etiologies of cardiomyopathy and are presumed to be helpful in assessing the extent of cardiac involvement of FD and in guiding or monitoring subsequent treatment. Early recognition from extra-cardiac red flag signs either in classic form or red flags from cardiac manifestations in cardiac variants, and awareness from multispecialty team work remains the cornerstone for timely managements and beneficial responses from therapeutic interventions (e.g. oral chaperone therapy or enzyme replacement therapy) prior to irreversible organ damage. We aim to summarize contemporary knowledge based on literature review and the gap or future perspectives in clinical practice of FD-related cardiomyopathy in an attempt to form a current expert consensus in Taiwan.