Experiences of a Community-Based Digital Intervention Among Older People Living in a Low-Income Neighborhood: Qualitative Study.

BACKGROUND: Older adults worldwide experienced heightened risks of depression, anxiety, loneliness, and poor mental well-being during the COVID-19 pandemic. During this period, digital technology emerged as a means to mitigate social isolation and enhance social connectedness among older adults. However, older adults' behaviors and attitudes toward the adoption and use of digital technology are heterogeneous and shaped by factors such as age, income, and education. Few empirical studies have examined how older adults experiencing social and economic disadvantages perceive the learning of digital tools. OBJECTIVE: This study aims to examine the motivations, experiences, and perceptions toward a community-based digital intervention among older adults residing in public rental flats in a low-income neighborhood. Specifically, we explored how their attitudes and behaviors toward learning the use of smartphones are shaped by their experiences related to age and socioeconomic challenges. METHODS: This study adopted a qualitative methodology. Between December 2020 and March 2021, we conducted semistructured in-depth interviews with 19 participants aged ≥60 years who had completed the community-based digital intervention. We asked participants questions about the challenges encountered amid the pandemic, their perceived benefits of and difficulties with smartphone use, and their experiences with participating in the intervention. All interviews were audio recorded and analyzed using a reflexive thematic approach. RESULTS: Although older learners stated varying levels of motivation to learn, most expressed ambivalence about the perceived utility and relevance of the smartphone to their current needs and priorities. While participants valued the social interaction with volunteers and the personalized learning model of the digital intervention, they also articulated barriers such as age-related cognitive and physical limitations and language and illiteracy that hindered their sustained use of these digital devices. Most importantly, the internalization of ageist stereotypes of being less worthy learners and the perception of smartphone use as being in the realm of the privileged other further reduced self-efficacy and interest in learning. CONCLUSIONS: To improve learning and sustained use of smartphones for older adults with low income, it is essential to explore avenues that render digital tools pertinent to their daily lives, such as creating opportunities for social connections and relationship building. Future studies should investigate the relationships between older adults' social, economic, and health marginality and their ability to access digital technologies. We recommend that the design and implementation of digital interventions should prioritize catering to the needs and preferences of various segments of older adults, while working to bridge rather than perpetuate the digital divide.

Risk Factors of Long-Term Sequelae After Transcatheter Closure of Perimembranous Ventricular Septal Defect in Young Children.

BACKGROUND: Complications arising from transcatheter closure of perimembranous ventricular septal defects (pmVSD) in children, such as residual shunts and aortic regurgitation (AR), have been observed. However, the associated risk factors remain unclear. This study identified risk factors linked with residual shunts and AR following transcatheter closure of pmVSD in children aged 2-12 years.Methods and Results: The medical records of 63 children with pmVSD and a pulmonary-to-systemic blood flow ratio <2.0 who underwent transcatheter closure between 2011 and 2018 were analyzed with a minimum 3-year follow-up. The success rate of transcatheter closure was 98.4%, with no emergency surgery, permanent high-degree atrioventricular block, or mortality. Defects ≥4.5 mm had significantly higher odds of persistent residual shunt (odds ratio [OR] 6.85; P=0.03). The use of an oversize device (≥1.5 mm) showed a trend towards reducing residual shunts (OR 0.23; P=0.06). Age <4 years (OR 27.38; 95% confidence interval [CI] 2.33-321.68) and perimembranous outlet-type VSD (OR 11.94, 95% CI 1.10-129.81) were independent risk factors for AR progression after closure. CONCLUSIONS: Careful attention is crucial for pmVSDs ≥4.5 mm to prevent persistent residual shunts in transcatheter closure. Assessing AR risk, particularly in children aged <4 years, is essential while considering the benefits of pmVSD closure.

Impact of Previous Conventional Cardiac Surgery on the Clinical Outcomes After Heart Transplantation.

The impact of the type, purpose, and timing of prior surgery on heart transplantation (HT) remains unclear. This study investigated the influence of conventional cardiac surgery (PCCS) on HT outcomes. This study analyzed HTs performed between 1999 and 2019 at a single institution. Patients were categorized into two groups: those with and without PCCS. Short-term outcomes, including post-transplant complications and mortality rates, were evaluated. Cox proportional and Kaplan-Meier survival analyses were used to identify risk factors for mortality and assess long-term survival, respectively. Of 368 patients, 29% had PCCS. Patients with PCCS had a higher incidence of post-transplant complications. The in-hospital and 1 year mortality rates were higher in the PCCS group. PCCS and cardiopulmonary bypass time were significant risk factors for 1 year mortality (hazard ratios = 2.485 and 1.005, respectively). The long-term survival rates were lower in the PCCS group, particularly in the first year. In sub-analysis, patients with ischemic cardiomyopathy and PCCS had the poorest outcomes. The era of surgery and timing of PCCS in relation to HT did not significantly impact outcomes. In conclusion, PCCS worsen the HT outcomes, especially in patients with ischemic etiology. However, the timing of PCCS and era of HT did not significantly affect this concern.

Smartphone ownership, digital literacy, and the mediating role of social connectedness and loneliness in improving the wellbeing of community-dwelling older adults of low socio-economic status in Singapore.

INTRODUCTION: During the COVID-19 pandemic, safe-distancing measures resulted in many community-dwelling older adults being socially isolated and lonely, with its attending negative impact on wellbeing and quality of life. While digital technology may have mitigated this, older adults of low socioeconomic status (SES) are more likely to be digitally excluded and hence susceptible to the adverse effects of social isolation and loneliness. This study aims to understand the factors that affect digital literacy, smartphone ownership, and willingness to participate in a digital literacy program (DLP), and to test the hypothesized relations between digital literacy, social connectedness, loneliness, wellbeing, and quality of life amongst community dwelling older adults of low SES. MATERIALS AND METHODS: A questionnaire assessing digital literacy, social connectedness, wellbeing and quality of life was administered. Socio-demographic variables, pre-existing internet-enabled, and willingness to participate in a home-based DLP was also collected. Logistic regression was used to identify demographic factors associated with digital literacy, smartphone ownership, and willingness to enroll in a DLP. Serial mediation analysis was also performed using a structural equation model framework. RESULTS: A total of 302 participants were recruited. Female gender, older age, lower education levels were associated with lower digital literacy. Those who owned a smartphone tended to be younger and better educated. Older adults who were better educated, of Chinese descent (the ethnic majority in Singapore), and who had lower digital literacy, were most willing to enroll in the digital literacy education program. Social-use digital literacy had a positive indirect effect on well-being ([Formula: see text]) and Quality of life ([Formula: see text]), mediated by social connectedness and loneliness. In contrast, instrumental-use digital literacy had a negative indirect effect on well-being ([Formula: see text]) and Quality of life ([Formula: see text]), mediated by social connectedness and loneliness. DISCUSSION: The results suggest there are demographic barriers to participation in DLPs and highlight the benefit of focusing on enhancing social-use digital literacy. Further study is needed to evaluate how well specific interventions to improve social-use digital literacy help to reduce social isolation and loneliness, and ultimately improve wellbeing and quality of life.

Prognostic Prediction Value and Biological Functions of Non-Apoptotic Regulated Cell Death Genes in Lung Adenocarcinoma.

Objective To explore the potential biological functions and prognostic prediction values of non-apoptotic regulated cell death genes (NARCDs) in lung adenocarcinoma.Methods Transcriptome data of lung adenocarcinoma were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. We identified differentially expressed NARCDs between lung adenocarcinoma tissues and normal tissues with R software. NARCDs signature was constructed with univariate Cox regression analysis and the least absolute shrinkage and selection operator Cox regression. The prognostic predictive capacity of NARCDs signature was assessed by Kaplan-Meier survival curve, receiver operating characteristic curve, and univariate and multivariate Cox regression analyses. Functional enrichment of NARCDs signature was analyzed with gene set variation analysis, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes. In addition, differences in tumor mutational burden, tumor microenvironment, tumor immune dysfunction and exclusion score, and chemotherapeutic drug sensitivity were analyzed between the high and low NARCDs score groups. Finally, a protein-protein interaction network of NARCDs and immune-related genes was constructed by STRING and Cytoscape software. Results We identified 34 differentially expressed NARCDs associated with the prognosis, of which 16 genes (ATIC, AURKA, CA9, ITGB4, DDIT4, CDK5R1, CAV1, RRM2, GAPDH, SRXN1, NLRC4, GLS2, ADRB2, CX3CL1, GDF15, and ADRA1A) were selected to construct a NARCDs signature. NARCDs signature was identified as an independent prognostic factor (P < 0.001). Functional analysis showed that there were significant differences in mismatch repair, p53 signaling pathway, and cell cycle between the high NARCDs score group and low NARCDs score group (all P < 0.05). The NARCDs low score group had lower tumor mutational burden, higher immune score, higher tumor immune dysfunction and exclusion score, and lower drug sensitivity (all P < 0.05). In addition, the 10 hub genes (CXCL5, TLR4, JUN, IL6, CCL2, CXCL2, ILA, IFNG, IL33, and GAPDH) in protein-protein interaction network of NARCDs and immune-related genes were all immune-related genes. Conclusion The NARCDs prognostic signature based on the above 16 genes is an independent prognostic factor, which can effectively predict the clinical prognosis of patients of lung adenocarcinoma and provide help for clinical treatment.

Validation of the European system for cardiac operative risk evaluation II in a large Taiwan cardiac surgical centre.

BACKGROUND: The European System for Cardiac Operative Risk Evaluation (EuroSCORE II) is a well-established scoring system for predicting mortality in cardiac surgery. This system was derived predominantly from a European patient cohort; however, no validation of this system has been conducted in Taiwan. We sought to assess the performance of EuroSCORE II at a tertiary centre. METHODS: The 2161 adult patients receiving cardiac surgery between 2017 and 2020 in our institution were included. RESULTS: Overall, the in-hospital mortality rate was 7.89%. The performance of EuroSCORE II was assessed using the area under the receiver operator curve (AUC) for discrimination and the Hosmer-Lemeshow (H-L) test for calibration. Data were analysed for type of surgery, risk stratification, and status of the operation. EuroSCORE II had good discriminative power (AUC=0.854, 95% Confidence Interval (CI): 0.822-0.885) and good calibration (χ2=5.19, p=0.82) for all types of surgery except ventricular assist devices (AUC=0.618, 95% CI: 0.497-0.738). EuroSCORE II also showed good calibration for most types of surgery except coronary artery bypass surgery (CABG) combined procedure (P=0.033), heart transplantation (HT) (P=0.017), and urgent operation (P=0.041). EuroSCORE II significantly underestimated the risk for CABG combined procedure and urgent operations, and overestimated the risk for HT. CONCLUSION: EuroSCORE II had satisfactory discrimination and calibration power to predict surgical mortality in Taiwan. However, the model is poorly calibrated for CABG combined procedure, HT, urgent operation, and, likely, lower- and higher-risk patients.

Preoperative chemoradiation-induced hematological toxicity and related vertebral dosimetry evaluations in patients with locally advanced gastric cancer: data from a phase III clinical trial.

BACKGROUND: To explore the hematological toxicity (HT) induced by neoadjuvant chemoradiotherapy (nCRT) compared with neoadjuvant chemotherapy (nCT) and to identify the appropriate vertebral body (VB) dosimetric parameters for predicting HT in patients with locally advanced gastric cancer (GC). METHODS: In the phase III study, 302 patients with GC from an ongoing multi-center randomized clinical trial (NCT01815853) were included. Patients from two major centers were grouped into training and external validation cohorts. The nCT group received three cycles of XELOX chemotherapy, while the nCRT received the same dose-reduced chemotherapy plus 45 Gy radiotherapy. The complete blood counts at baseline, during neoadjuvant treatment, and in the preoperative period were compared between the nCT and nCRT groups. The VB was retrospectively contoured and the dose-volume parameters were extracted in the nCRT group. Patients' clinical characteristics, VB dosimetric parameters, and HTs were statistically analyzed. Instances of HT were graded according to the Common Terminology Criteria for Adverse Events v5.0 (CTCAE v5.0). The receiver operating characteristic (ROC) curves were generated to identify the optimal cut-off points for dosimetric variables and verify the prediction efficiency of the dosimetric index in both training and external validation cohorts. RESULTS: In the training cohort, 27.4% Grade 3 + HTs were noted in the nCRT group and 16.2% in the nCT group (P = 0.042). A similar result was exhibited in the validation cohort, with 35.0% Grade 3 + HTs in the nCRT group and 13.2% in the nCT group (P = 0.025). The multivariate analysis of the training cohort revealed that V5 was associated with Grade 3 + leukopenia (P = 0.000), Grade 3 + thrombocytopenia (P = 0.001), and Grade 3 + total HTs (P = 0.042). The Spearman correlation analysis identified a significant correlation of V5 with the white blood cell nadir (P = 0.0001) and platelet nadir (P = 0.0002). The ROC curve identified the optimal cut-off points for V5 and showed that V5 < 88.75% could indicate a decreased risk of Grade 3 + leukopenia, thrombocytopenia, and total HTs in the training as well as the external validation cohorts. CONCLUSIONS: Compared with nCT, nCRT could increase the risk of Grade 3 + HT in patients with locally advanced GC. Dose constraints of V5 < 88.75% in irradiated VB could reduce the incidence of Grade 3 + HT.

Validation of Multi-epitope Peptides Encapsulated in PLGA Nanoparticles Against Influenza A Virus.

BACKGROUND: Influenza is a highly contagious respiratory disease which poses a serious threat to public health globally, causing severe diseases in 3-5 million humans and resulting in 650,000 deaths annually. The current licensed seasonal influenza vaccines lacked cross-reactivity against novel emerging influenza strains as they conferred limited neutralising capabilities. To address the issue, we designed a multi-epitope peptide-based vaccine delivered by the self-adjuvanting PLGA nanoparticles against influenza infections. METHODS: A total of six conserved peptides representing B- and T-cell epitopes of Influenza A were identified and they were formulated in either incomplete Freund's adjuvant containing CpG ODN 1826 or being encapsulated in PLGA nanoparticles for the evaluation of immunogenicity in BALB/c mice. RESULTS: The self-adjuvanting PLGA nanoparticles encapsulating the six conserved peptides were capable of eliciting the highest levels of IgG and IFN- γ producing cells. In addition, the immunogenicity of the six peptides encapsulated in PLGA nanoparticles showed greater humoral and cellular mediated immune responses elicited by the mixture of six naked peptides formulated in incomplete Freund's adjuvant containing CpG ODN 1826 in the immunized mice. Peptide 3 from the mixture of six peptides was found to exert necrotic effect on CD3+ T-cells and this finding indicated that peptide 3 should be removed from the nanovaccine formulation. CONCLUSION: The study demonstrated the self-adjuvanting properties of the PLGA nanoparticles as a delivery system without the need for incorporation of toxic and costly conventional adjuvants in multi-epitope peptide-based vaccines.

Neoadjuvant chemoradiotherapy induced lymphopenia in gastric cancer and associations with spleen dosimetry and survival outcomes.

Background: Few studies concentrate on spleen dosimetry of radiotherapy for gastric cancer (GC). Although there is no consensus on the spleen dose-volume threshold for lymphopenia, several studies indicated that the higher the spleen dose, the higher the risk of lymphopenia. This study aimed to identify the appropriate spleen dosimetric parameters for predicting grade 4 + lymphopenia in patients with locally advanced GC. Material and methods: A total of 295 patients treated with nCRT and nChT from June 2013 to December 2021 at two major centers were included, of whom 220 were assigned to the training cohort and 75 to the external validation cohort. Results: Grade 4 + lymphopenia was more common in the nCRT than in the nChT group (49.5% vs. 0, P < 0.001 in the training cohort; 25.0% vs. 0, P = 0.001 in the external validation cohort). Age ≥ 60 years (P = 0.006), lower pretreatment absolute lymphocyte count (P = 0.001), higher spleen volume (SPV) (P = 0.001), and higher V20 (P = 0.003) were significant risk factors of grade 4 + lymphopenia for patients treated with nCRT. Patients with grade 4 + lymphopenia had significantly worse PFS (P = 0.043) and showed a negative correlation trend with OS (P = 0.07). Limiting V20 to < 84.5% could decrease the incidence of grade 4 + lymphopenia by 35.7%. The predictive effectiveness of the multivariable model in the training and external validation cohorts was 0.880 and 0.737, respectively. Conclusion: Grade 4 + lymphopenia during nCRT was more common than nChT, and was associated with a worse PFS in GC patients. Constraining the spleen V20 to < 84.5% may indirectly improve outcomes through lymphocyte preservation.

Total Anomalous Pulmonary Venous Connection: Surgical Outcomes and Risk Factors for Postoperative Pulmonary Vein Obstruction.

Background: Total anomalous pulmonary venous connection (TAPVC) is a fatal congenital cardiac anomaly that requires urgent surgical intervention. The development of postoperative pulmonary vein obstruction (PVO) negatively impacts long-term survival. Objectives: The present study aimed to evaluate the surgical outcomes of TAPVC repair and risk factors associated with postoperative PVO. Methods: Patients who underwent primary TAPVC repair at our institute between 2004 and 2022 were retrospectively enrolled, and those with right atrial isomerism and single ventricle physiology were excluded. Factors associated with survival and postoperative PVO were analyzed. Results: A total of 116 patients were enrolled in the present study. The early mortality rate was 6.9%. Nineteen patients (16.4%) developed postoperative PVO within a median time of 59 days of the primary repair, of whom 10 were successfully relieved without any recurrent obstruction. In long-term follow-up, patients with postoperative PVO had significantly lower long-term survival rates than those without postoperative PVO [57.9%, 95% confidence interval (CI) = 34.8-79.5%; vs. 90.4%, 95% CI = 83-96.6% at 10 years, p < 0.001]. Risk factors for postoperative PVO development included lower body weight, younger age, preoperative mechanical ventilation, preoperative inotrope use, and emergency operation. Conclusions: Postoperative PVO was significantly associated with a higher long-term mortality rate after primary TAPVC repair, with the risk being higher in patients with critical preoperative status. The long-term outcome was good for patients in whom the obstruction was successfully relieved. Early detection and prompt intervention for postoperative PVO after TAPVC repair can improve overall survival in these patients.

Biventricular Repair for Aortic Atresia, Ventricular Septal Defect, and Type C Interrupted Aortic Arch.

Interrupted aortic arch is a rare congenital heart defect. Among patients with interrupted aortic arch, an interruption between the innominate artery and left common carotid artery (type C) is the rarest. Herein, we report the case of a neonate with aortic atresia, ventricular septal defect, type C interrupted aortic arch, and aberrant right subclavian artery who underwent Norwood stage I operation and staged biventricular repair. Due to aortic atresia, coronary artery perfusion was retrograde from the right common carotid artery. The surgical technique and special considerations for cardiopulmonary bypass are presented.

Role of percutaneous pulmonary artery cannulation in extracorporeal life support for acute cardiac failure: A single-center case series.

BACKGROUND: Pulmonary artery (PA) cannulation is an effective extracorporeal life support (ECLS) management for left ventricular (LV) decompression or right ventricular (RV) support. This case series explores the results of PA cannulation during ECLS for acute cardiac failure. METHODS: Patients receiving percutaneous PA cannulation between January 2017 and December 2020 in a single institution were retrospectively reviewed. Patients receiving PA cannulation by a surgical cutdown method were excluded. Based on the hemodynamic needs of the patients, percutaneous PA cannulation was applied with ECLS for LV unloading and/or RV support. The primary endpoint was the successful weaning from circulatory support. The secondary endpoints included 30-day or in-hospital mortality, significant periprocedural complications, and successful hospital discharge without major complications. RESULTS: Fifteen patients (13 men, age range 11.2-70.8 years) presented acute heart failure and were initially managed by conventional ECLS mode. Percutaneous PA cannulation was performed for LV unloading in 13 patients (86.67%) and isolated RV circulatory support in two patients (13.33%). Weaning from circulatory support was achieved in 11 patients (73.33%). No significant periprocedural complication, including bleeding, infection, or vascular event requiring surgical exploration, was reported. The 30-day or in-hospital mortality rate was 33.33%. Eight cases (53.33%) were successfully discharged without major complications, including permanent stroke or the need for long-term hemodialysis. CONCLUSIONS: PA cannulation, especially percutaneously performed, was effective and safe for LV unloading and/or RV support during ECLS. Further investigation is required to confirm the efficacy and safety of our approach and management in a larger patient population.

Outcomes of pediatric patients supported with ventricular assist devices single center experience.

BACKGROUND: There has been a remarkable increase in the number of pediatric ventricular assist device (VAD) implanted over the past decade. Asian pediatric heart centers had not participated in the multicenter registries among the Western countries. This article aimed to report the outcomes of pediatric VAD in our hospital. METHODS: The study enrolled all patients aged <18 years at the time of VAD implantation in our institution between 2008 and 2021. RESULTS: There were 33 patients with diagnosis of acute fulminant myocarditis (n = 9), congenital heart disease (n = 5), dilated cardiomyopathy (n = 16), and others. Paracorporeal continuous-flow pump was the most frequently implanted (n = 27). Most of the devices were implanted in patients with INTERMACS profile 1 (n = 24). The median duration on VAD was 22 days (range 2-254). The proportion of patients attaining positive outcomes (alive on device, bridge to transplantation or recovery) was 72.7% at 1 month, 67.7% at 3 months, and 67.7% at 6 months. Most of the deaths on device occurred within the first month post-implant (n = 9), with neurological complications being the most frequent cause of death. All recovered cases were successfully weaned off the device within the first month of implantation. CONCLUSION: We demonstrated a favorable outcome in pediatric patients supported with VAD at our institution.

Nanovaccines against Viral Infectious Diseases.

Infectious diseases have always been regarded as one of the greatest global threats for the last century. The current ongoing COVID-19 pandemic caused by SARS-CoV-2 is living proof that the world is still threatened by emerging infectious diseases. Morbidity and mortality rates of diseases caused by Coronavirus have inflicted devastating social and economic outcomes. Undoubtedly, vaccination is the most effective method of eradicating infections and infectious diseases that have been eradicated by vaccinations, including Smallpox and Polio. To date, next-generation vaccine candidates with novel platforms are being approved for emergency use, such as the mRNA and viral vectored vaccines against SARS-CoV-2. Nanoparticle based vaccines are the perfect candidates as they demonstrated targeted antigen delivery, improved antigen presentation, and sustained antigen release while providing self-adjuvanting functions to stimulate potent immune responses. In this review, we discussed most of the recent nanovaccines that have found success in immunization and challenge studies in animal models in comparison with their naked vaccine counterparts. Nanovaccines that are currently in clinical trials are also reviewed.

Building Digital Literacy in Older Adults of Low Socioeconomic Status in Singapore (Project Wire Up): Nonrandomized Controlled Trial.

BACKGROUND: In a rapidly digitalizing world, the inability of older adults to leverage digital technology has been associated with weaker social connections and poorer health outcomes. Despite the widespread digital adoption in Singapore, older adults, especially those of lower socioeconomic status (SES), still face difficulties in adopting information and communications technology and are typically digitally excluded. OBJECTIVE: We aimed to examine the impact of the volunteer-led, one-on-one, and home-based digital literacy program on digital literacy and health-related outcomes such as self-reported loneliness, social connectedness, quality of life, and well-being for older adults of low SES. METHODS: A nonrandomized controlled study was carried out in Singapore between July 2020 and November 2021 involving 138 digitally excluded community-dwelling older adults aged ≥55 years and of lower SES. Older adults awaiting participation in the program served as controls. Older adults under the intervention were equipped with a smartphone and cellular data, underwent fortnightly to monthly digital literacy training with volunteers to learn digital skills, and digitally connected to their existing social networks. Primary outcome was the improvement in self-reported digital literacy. Secondary outcomes included improvements in University of California, Los Angeles 3-item loneliness scale, Lubben Social Network Scale-6, EQ-5D-3L and EQ visual analogue scale scores, and Personal Wellbeing Score. RESULTS: There were significant improvements in digital literacy scores in the intervention group as compared to controls (mean difference 2.28, 95% CI 1.37-3.20; P<.001). Through multiple linear regression analyses, this difference in digital literacy scores remained independently associated with group membership after adjusting for differences in baseline scores, age, gender, education, living arrangement, housing type, and baseline social connectivity and loneliness status. There was no statistically significant difference in University of California, Los Angeles 3-item loneliness scale, Lubben Social Network Scale-6, Personal Wellbeing Score, or EQ-5D Utility and visual analogue scale score. CONCLUSIONS: This study adds to the growing research on digital inclusion by showing that a volunteer-led, one-on-one, and home-based digital literacy program contributed to increase digital literacy in older adults of low SES. Future studies should look into developing more older adult-friendly digital spaces and technology design to encourage continued digital adoption in older adults and, eventually, impact health-related outcomes.

Huoxue Qingre decoction used for treatment of coronary heart disease network analysis and metabolomic evaluation.

Objective: Network pharmacology provides new methods and references for the research of traditional Chinese medicine, but some problems remain, such as single evaluation components and index methods, imperfect relevant databases, unscientific prediction results, and lack of verification of results. Herein, we used a modified network pharmacology research method to explore the potential network analysis mechanism of Huoxue Qingre decoction in the treatment of coronary heart disease and utilized clinical trials for assessment. Methods: Based on literature research, the targets corresponding to the drug were obtained with the assistance of the TCMSP database and Swiss Target Prediction, and the target proteins were corrected using the UniProt database. The targets related to coronary heart disease was obtained through the GeneCards database. A protein-protein interaction network diagram was constructed, and a "component-intersection target" network diagram was drawn based on Cytoscape 3.6.2 software. The mapped targets were imported into the DAVID bioinformatics platform, which underwent Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and the network pharmacology prediction results were evaluated through clinical trials. Results: We obtained 151 compounds related to Huoxue Qingre decoction, 286 genes after evaluation and deduplication, and 426 genes related to coronary heart disease. Finally, 81 common target genes were obtained with 32 pathways according to the KEGG pathway enrichment analysis. The validation results of the clinical trials showed that a total of 98 differential metabolites were found in the treatment of coronary heart disease with Huoxue Qingre decoction, involving a total of 16 metabolic pathways. Compared with the network pharmacology prediction results, it was found that only the pathways in cancer (hsa05200) were the common pathways in the top 32 signaling pathways predicted by network pharmacology. The expanded network pharmacology prediction results revealed that the sphingolipid signaling pathway (hsa04071) and prostate cancer pathway (hsa05215) matched the predicted metabolic pathways, with differential metabolites of N-oleoyl-D-sphingomyelin and 1-methyl-6-phenyl-1h-imidazole[4,5-b]pyridine-2-amine. Conclusion: Through the network analysis and metabolomic evaluation, there may be three signaling pathways that involve the Huoxue Qingre decoction in the treatment of coronary heart disease: pathways in cancer (hsa05200), sphingolipid signaling pathway (hsa04071), and prostate cancer pathway (hsa05215).

Extreme size mismatch: bronchus compression by an oversized donor heart in small children.

Studies have suggested that a more liberal criterion of donor-recipient weight ratio (DRWR) is associated with superior waitlist survival without compromising posttransplant outcomes in selected critically ill patients. Successful transplantation of an extremely oversized donor heart into a small recipient is herein described. A 2-year-old girl accepted a size-mismatched adult donor heart offer (DRWR of 4.4) due to frequent complications with a left ventricular assist device. During the immediate postoperative period, spatial constraints within the thoracic cavity compromised graft function. Computed tomography revealed severe compression of the left bronchus due to the oversized allograft with lobar collapse of the left lung. With temporary extracorporeal membrane oxygenation support, graft function improved within 1 month after transplantation. Subsequent adaptive size remodeling of the transplanted heart with concomitant left bronchus re-expansion was observed within 6 months after transplantation. Despite a complicated posttransplant recovery, the patient was discharged home with minimal respiratory sequelae. Our report describes an alternative strategy for managing early morbidities related to an oversized graft and supports extending the criteria of size matching in pediatric heart transplantations.

Microrna-486-5P Regulates Human Pulmonary Artery Smooth Muscle Cell Migration via Endothelin-1.

Pulmonary arterial hypertension (PAH) is a fatal or life-threatening disorder characterized by elevated pulmonary arterial pressure and pulmonary vascular resistance. Abnormal vascular remodeling, including the proliferation and phenotypic modulation of pulmonary artery smooth muscle cells (PASMCs), represents the most critical pathological change during PAH development. Previous studies showed that miR-486 could reduce apoptosis in different cells; however, the role of miR-486 in PAH development or HPASMC proliferation and migration remains unclear. After 6 h of hypoxia treatment, miR-486-5p was significantly upregulated in HPASMCs. We found that miR-486-5p could upregulate the expression and secretion of ET-1. Furthermore, transfection with a miR-486-5p mimic could induce HPASMC proliferation and migration. We also found that miRNA-486-5p could downregulate the expression of SMAD2 and the phosphorylation of SMAD3. According to previous studies, the loss of SMAD3 may play an important role in miRNA-486-5p-induced HPASMC proliferation. Although the role of miRNA-486-5p in PAH in in vivo models still requires further investigation and confirmation, our findings show the potential roles and effects of miR-486-5p during PAH development.

Pharmacological properties of total flavonoids in Scutellaria baicalensis for the treatment of cardiovascular diseases.

BACKGROUND: Scutellaria baicalensis, a medicinal herb belonging to the Lamiaceae family, has been recorded in the Chinese, European, and British Pharmacopoeias. The medicinal properties of this plant are attributed to the total flavonoids of Scutellaria baicalensis (TFSB), particularly the main component, baicalin. This study provides a systematic and comprehensive list of the identified TFSB components and their chemical structures. The quality control process, pharmacokinetics, clinical application, and safety of Scutellaria baicalensis are discussed, and its pharmacological effect on cardiovascular diseases (CVDs) is detailed. Finally, the future research trends and prospects of this medicinal plant are provided. METHODS: The Chinese and English papers related to TFSB were collected from the PubMed and CNKI databases using the relevant keywords. To highlight the pharmacological mechanism, clinical application, and safety of TFSB, the collected articles were screened and classified based on their research content. RESULTS: TFSB contains at least 100 different kinds of flavonoids, of which baicalin, baicalein, wogonin, wogonoside, scutellarin, and scutellarein are the main active ingredients. The preparation process of TFSB is relatively well established, and the extraction rate can be significantly increased by enzymatic pretreatment and ultrasonication. The low oral availability of TFSB may be effectively enhanced using nanoformulations. The available pharmacokinetic data show that flavonoid glycosides and aglycones with the same parent nucleus may be converted to structures that are conducive to absorption in vivo. Moreover, TFSB can protect against CVDs by inhibiting apoptosis, regulating oxidative stress response, participating in inflammatory response, protecting against myocardial fibrosis, inhibiting myocardial hypertrophy, and regulating blood vessels. In terms of clinical application and animal safety, the available studies show that TFSB can be applied in a wide range of clinical treatments and is safe to use is animals. CONCLUSION: This article systematically reviews the therapeutic effect and underlying pharmacological mechanism of TFSB against CVDs. The available studies clearly suggest that TFSB has great potential for the treatment of CVDs and is worthy of in-depth research and development.