Sex Differences in Quality of Life and Clinical Outcomes in Patients with Heart Failure

Background: Heart failure (HF) is generally associated with poor quality of life (QoL). Limited data are available characterizing health-related QoL (HRQL) in Chinese patients with HF. Methods: We used the Minnesota Living with Heart Failure Questionnaire (MLHFQ) to record QoL in 4082 patients with HF from China who were followed up over 12 months in the Heart Failure Registry of Patient Outcomes (HERO) study. Baseline HRQL and differences in QoL between women and men with heart failure were compared. We used multivariable Cox regression with adjustment for variables to assess the association between MLHFQ summary scores and a composite of all-cause mortality and HF hospitalization. Result: At baseline, the mean MLHFQ in the overall population was 42.9 ± 19.57; the scores for physical and emotional domains were 22.0 ± 8.69 and 8.66 ± 6.08, respectively. Women had a higher (poorer) MLHFQ summary score (44.27 ± 19.13) than men (41.63 ± 19.90) (P<0.001). Female patients also had higher MLHFQ physical and emotional scores than male patients (P<0.001). The specific scores of the questionnaire were higher in women than men. NYHA class was the strongest independent predictor of MLHFQ score (β=6.12 unit increment; P<0.001). Sex was not independently associated with higher MLHFQ scores after multivariable adjustments. The 12-month mortality in the overall cohort was 19.6%, the hospitalization rate was 24.4%, and the composite endpoint was 40.15%. A 10-point increase in MLHFQ score was associated with higher risk of mortality (female and male HRs=1.19 [95% CI 1.12–1.26]; P<0.001 and 1.18 [95% CI 1.12–1.24]; P<0.001, respectively) and composite outcomes (HRs=1.08 [95% CI 1.04–1.13]; P<0.001 and 1.11 [95% CI 1.07–1.14]; P<0.001, respectively). Females did not show a significant association between HRQL and hospitalization (HR=1.04 [95% CI 0.99–1.09]; P=0.107). Conclusion: Quality of life was largely poorer in women than men, but was similar between sexes in terms of physical burden and emotional limitation. HRQL is an independent predictor of all-cause death and HF hospitalization in patients with HF

Trans-omics biomarker model improves prognostic prediction accuracy for early-stage lung adenocarcinoma

Limited studies have focused on developing prognostic models with trans-omics biomarkers for early-stage lung adenocarcinoma (LUAD). We performed integrative analysis of clinical information, DNA methylation, and gene expression data using 825 early-stage LUAD patients from 5 cohorts. Ranger algorithm was used to screen prognosis-associated biomarkers, which were confirmed with a validation phase. Clinical and biomarker information was fused using an iCluster plus algorithm, which significantly distinguished patients into high- and low-mortality risk groups (Pdiscovery = 0.01 and Pvalidation = 2.71×10-3). Further, potential functional DNA methylation-gene expression-overall survival pathways were evaluated by causal mediation analysis. The effect of DNA methylation level on LUAD survival was significantly mediated through gene expression level. By adding DNA methylation and gene expression biomarkers to a model of only clinical data, the AUCs of the trans-omics model improved by 18.3% (to 87.2%) and 16.4% (to 85.3%) in discovery and validation phases, respectively. Further, concordance index of the nomogram was 0.81 and 0.77 in discovery and validation phases, respectively. Based on systematic review of published literatures, our model was superior to all existing models for early-stage LUAD. In summary, our trans-omics model may help physicians accurately identify patients with high mortality risk

SIPA1L3 methylation modifies the benefit of smoking cessation on lung adenocarcinoma survival: an epigenomic-smoking interaction analysis

Smoking cessation prolongs survival and decreases mortality of patients with non‐small‐cell lung cancer (NSCLC). In addition, epigenetic alterations of some genes are associated with survival. However, potential interactions between smoking cessation and epigenetics have not been assessed. Here, we conducted an epigenome‐wide interaction analysis between DNA methylation and smoking cessation on NSCLC survival. We used a two‐stage study design to identify DNA methylation-smoking cessation interactions that affect overall survival for early‐stage NSCLC. The discovery phase contained NSCLC patients from Harvard, Spain, Norway, and Sweden. A histology‐stratified Cox proportional hazards model adjusted for age, sex, clinical stage, and study center was used to test DNA methylation-smoking cessation interaction terms. Interactions with false discovery rate‐q ≤ 0.05 were further confirmed in a validation phase using The Cancer Genome Atlas database. Histology‐specific interactions were identified by stratification analysis in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients. We identified one CpG probe (cg02268510SIPA1L3) that significantly and exclusively modified the effect of smoking cessation on survival in LUAD patients [hazard ratio (HR)interaction = 1.12; 95% confidence interval (CI): 1.07-1.16; P = 4.30 × 10-7]. Further, the effect of smoking cessation on early‐stage LUAD survival varied across patients with different methylation levels of cg02268510SIPA1L3. Smoking cessation only benefited LUAD patients with low methylation (HR = 0.53; 95% CI: 0.34-0.82; P = 4.61 × 10-3) rather than medium or high methylation (HR = 1.21; 95% CI: 0.86-1.70; P = 0.266) of cg02268510SIPA1L3. Moreover, there was an antagonistic interaction between elevated methylation of cg02268510SIPA1L3 and smoking cessation (HRinteraction = 2.1835; 95% CI: 1.27-3.74; P = 4.46 × 10−3). In summary, smoking cessation benefited survival of LUAD patients with low methylation at cg02268510SIPA1L3. The results have implications for not only smoking cessation after diagnosis, but also possible methylation‐specific drug targeting

Poly(lactic-co-glycolic) Acid/Nanohydroxyapatite Scaffold Containing Chitosan Microspheres with Adrenomedullin Delivery for Modulation Activity of Osteoblasts and Vascular Endothelial Cells

Adrenomedullin (ADM) is a bioactive regulatory peptide that affects migration and proliferation of diverse cell types, including endothelial cells, smooth muscle cells, and osteoblast-like cells. This study investigated the effects of sustained release of ADM on the modulation activity of osteoblasts and vascular endothelial cells in vitro. Chitosan microspheres (CMs) were developed for ADM delivery. Poly(lactic-co-glycolic) acid and nano-hydroxyapatite were used to prepare scaffolds containing microspheres with ADM. The CMs showed rough surface morphology and high porosity, and they were well-distributed. The scaffolds exhibited relatively uniform pore sizes with interconnected pores. The addition of CMs improved the mechanical properties of the scaffolds without affecting their high porosity. In vitro degradation tests indicated that the addition of CMs increased the water absorption of the scaffolds and inhibited pH decline of phosphate-buffered saline medium. The expression levels of osteogenic-related and angiogenic-related genes were determined in MG63 cells and in human umbilical vein endothelial cells cultured on the scaffolds, respectively. The expression levels of osteogenic-related and angiogenic-related proteins were also detected by western blot analysis. Their expression levels in cells were improved on the ADM delivery scaffolds at a certain time point. The in vitro evaluation suggests that the microsphere-scaffold system is suitable as a model for bone tissue engineering

Mesenchymal Stem Cells Enhance Therapeutic Effect and Prevent Adverse Gastrointestinal Reaction of Methotrexate Treatment in Collagen-Induced Arthritis

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by articular destruction and functional loss. Methotrexate (MTX) is effective in RA treatment. However, MTX induces several adverse events and 20%-30% of patients do not respond to MTX. Thus, it is urgent to enhance the therapeutic effects and reduce the side effects of MTX. Recent studies showed that mesenchymal stem cells (MSCs) were participants in anti-inflammation, immunoregulation, and tissue regeneration. However, whether the combined application of MSCs and MTX promotes the therapeutic effects and reduces the side effects of MTX has not been studied. In this study, we used bovine type II collagen to induce rheumatoid arthritis in mice (collagen-induced arthritis, CIA). Then, CIA mice were subjected to MTX or MSC treatment, or both. The therapeutic effect and adverse events of different treatments on RA were evaluated with micro-CT, HE staining, and immunohistochemistry in vivo. Apoptosis and proliferation of MODE-K cells were measured after treated with MTX or/and cocultured with UCs. To test M2 polarization, Raw264.7 macrophages were stimulated by MTX with different concentrations or cocultured with UCs. We found that the combined application of MSCs and MTX increased the therapeutic effects on RA, as evidenced by decreased arthritis score, inflammatory responses, and mortality. Moreover, in this combination remedy, MTX prefers to suppress inflammation by facilitating macrophage polarization to M2 type while UCs prefer to eliminate gastrointestinal side effects of MTX via mitigating the apoptosis of intestinal epithelial cells. Thus, a combination of MTX and UCs is a promising strategy for RA treatment

Early Sucrose Degradation and the Dominant Sucrose Cleavage Pattern Influence Lycoris sprengeri Bulblet Regeneration In Vitro

Bulblet formation and development determine the quantitative and qualitative traits, respectively, of bulb yield for most flowering bulbs. For Lycoris species, however, the underlying molecular mechanism remains elusive. Here, clonal bulblets of Lycoris sprengeri (Ls) derived from the same probulb were used as explants to establish efficient and inefficient in vitro regeneration systems by adjusting the 6-benzyladenine (BA) concentrations in media. BA application did not change the biological processes among groups but led to earlier decreases in sucrose and total soluble sugar (TSS) contents. Correlation analyses showed that the BA treatments changed the interaction between carbohydrate and endogenous hormone contents during bulblet regeneration. We found that two sucrose degradation enzyme-related genes, cell wall invertase (CWIN) and sucrose synthase, exhibited exactly opposite expression patterns during the competence stage. In addition, the regeneration system that obtained more bulblets showed significantly higher expression of LsCWIN2 than those that obtained fewer bulblets. Our data demonstrate the essential role of BA in accelerating sucrose degradation and the selection of a dominant sucrose cleavage pattern at the competence stage of in vitro bulblet regeneration. We propose that a relatively active CWIN-catalyzed pathway at the competence stage might promote bulblet regeneration, thus influencing bulb yield

Association Between Socioeconomic Status and Adherence to Fecal Occult Blood Tests in Colorectal Cancer Screening Programs: Systematic Review and Meta-Analysis of Observational Studies

BackgroundScreening adherence is important in reducing colorectal cancer (CRC) incidence and mortality. Disparity in CRC screening adherence was observed in populations of different socioeconomic status (SES), but the direction and strength of the association remained unclear. ObjectiveWe aimed to systematically review all the observational studies that have analyzed the association between SES and adherence to organized CRC screening based on fecal occult blood tests. MethodsWe systematically reviewed the studies in PubMed, Embase, and Web of Science and reference lists of relevant reviews from the inception of the database up until June 7, 2023. Individual SES, neighborhood SES, and small-area SES were included, while any SES aggregated by geographic areas larger than neighbors were excluded. Studies assessing SES with any index or score combining indicators of income, education, deprivation, poverty, occupation, employment, marital status, cohabitation, and others were included. A random effect model meta-analysis was carried out for pooled odds ratios (ORs) and relative risks for adherence related to SES. ResultsOverall, 10 studies, with a total of 3,542,379 participants and an overall adherence rate of 64.9%, were included. Compared with low SES, high SES was associated with higher adherence (unadjusted OR 1.73, 95% CI 1.42-2.10; adjusted OR 1.53, 95% CI 1.28-1.82). In the subgroup of nonindividual-level SES, the adjusted association was significant (OR 1.57, 95% CI 1.26-1.95). However, the adjusted association was insignificant in the subgroup of individual-level SES (OR 1.46, 95% CI 0.98-2.17). As for subgroups of the year of print, not only was the unadjusted association significantly stronger in the subgroup of early studies (OR 1.97, 95% CI 1.59-2.44) than in the subgroup of late studies (OR 1.43, 95% CI 1.31-1.56), but also the adjusted one was significantly stronger in the early group (OR 1.86, 95% CI 1.43-2.42) than in the late group (OR 1.26, 95% CI 1.14-1.39), which was consistent and robust. Despite being statistically insignificant, the strength of the association seemed lower in studies that did not adjust for race and ethnicity (OR 1.31, 95% CI 1.21-1.43) than the overall estimate (OR 1.53, 95% CI 1.28-1.82). ConclusionsThe higher-SES population had higher adherence to fecal occult blood test–based organized CRC screening. Neighborhood SES, or small-area SES, was more competent than individual SES to be used to assess the association between SES and adherence. The disparity in adherence between the high SES and the low SES narrowed along with the development of interventions and the improvement of organized programs. Race and ethnicity were probably important confounding factors for the association

Combining fecal immunochemical testing and questionnaire-based risk assessment in selecting participants for colonoscopy screening in the Chinese National Colorectal Cancer Screening Programs: A population-based cohort study.

BackgroundScreening reduces colorectal cancer (CRC) burden by allowing early resection of precancerous and cancerous lesions. An adequate selection of high-risk individuals and a high uptake rate for colonoscopy screening are critical to identifying people more likely to benefit from screening and allocating healthcare resources properly. We evaluated whether combining a questionnaire-based interview for risk factors with fecal immunochemical test (FIT) outcomes for high-risk assessment is more efficient and economical than a questionnaire-based interview-only strategy.Methods and findingsIn this multicenter, population-based, prospective cohort study, we enrolled community residents aged 40 to 74 years in 29 provinces across China. From 2016 to 2020, a total of 1,526,824 eligible participants were consecutively enrolled in the Cancer Screening Program in Urban China (CanSPUC) cohort, and 940,605 were enrolled in the Whole Life Cycle of Cancer Screening Program (WHOLE) cohort, with follow-up to December 31, 2022. The mean ages were 56.89 and 58.61 years in CanSPUC and WHOLE, respectively. In the WHOLE cohort, high-risk individuals were identified by combining questionnaire-based interviews to collect data on risk factors (demographics, diet history, family history of CRC, etc.) with FIT outcomes (RF-FIT strategy), whereas in the CanSPUC cohort, high-risk individuals were identified using only interview-based data on risk factors (RF strategy). The primary outcomes were participation rate and yield (detection rate of advanced neoplasm, early-stage detection rate of CRCs [stage I/II], screening yield per 10,000 invitees), which were reported for the entire population and for different gender and age groups. The secondary outcome was the cost per case detected. In total, 71,967 (7.65%) and 281,985 (18.47%) individuals were identified as high-risk and were invited to undergo colonoscopy in the RF-FIT group and RF group, respectively. The colonoscopy participation rate in the RF-FIT group was 26.50% (19,071 of 71,967) and in the RF group was 19.54% (55,106 of 281,985; chi-squared test, p ConclusionsColonoscopy participation and screening yield were better with the RF-FIT strategy. The association with CRC incidence and mortality reduction should be evaluated after long-term follow-up