Construction of a metabolism-malnutrition-inflammation prognostic risk score in patients with heart failure with preserved ejection fraction: a machine learning based Lasso-Cox model.

BACKGROUND: Metabolic disorder, malnutrition and inflammation are involved and interplayed in the mechanisms of heart failure with preserved ejection fraction (HFpEF). We aimed to construct a Metabolism-malnutrition-inflammation score (MIS) to predict the risk of death in patients with HFpEF. METHODS: We included patients diagnosed with HFpEF and without infective or systemic disease. 20 biomarkers were filtered by the Least absolute shrinkage and selection operator (Lasso)-Cox regression. 1000 times bootstrapping datasets were generated to select biomarkers that appeared above 95% frequency in repetitions to construct the MIS. RESULTS: Among 1083 patients diagnosed with HFpEF, 342 patients (31.6%) died during a median follow-up period of 2.5 years. The MIS was finally constructed based on 6 biomarkers, they were albumin (ALB), red blood cell distribution width-standard deviation (RDW-SD), high-sensitivity C-reactive protein (hs-CRP), lymphocytes, triiodothyronine (T3) and uric acid (UA). Incorporating MIS into the basic predictive model significantly increased both discrimination (∆C-index = 0.034, 95% CI 0.013-0.050) and reclassification (IDI, 6.6%, 95% CI 4.0%-9.5%; NRI, 22.2% 95% CI 14.4%-30.2%) in predicting all-cause mortality. In the time-dependent receiver operating characteristic (ROC) analysis, the mean area under the curve (AUC) for the MIS was 0.778, 0.782 and 0.772 at 1, 3, and 5 years after discharge in the cross-validation sets. The MIS was independently associated with all-cause mortality (hazard ratio: 1.98, 95% CI [1.70-2.31], P < 0.001). CONCLUSIONS: A risk score derived from 6 commonly used inflammatory, nutritional, thyroid and uric acid metabolic biomarkers can effectively identify high-risk patients with HFpEF, providing potential individualized management strategies for patients with HFpEF.

Is the transection of the hernia sac during laparoscopic inguinal hernioplasty safe and feasible? An updated systematic review and meta-analysis.

There is a debate over whether to transect or completely reduce the hernia sac during laparoscopic tension-free repair of inguinal hernia. This study endeavors to systematically assess the efficacy and safety of two approaches, namely transected sac (TS) and completely reduced sac (RS), in laparoscopic tension-free repair of inguinal hernia. Utilizing a meta-analysis methodology, we aim to provide a comprehensive analysis of these techniques. A comprehensive search was conducted across PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases to identify comparative studies focusing on laparoscopic tension-free repair of inguinal hernia, specifically comparing TS and RS techniques. The selected studies were subjected to meta-analysis using RevMan 5.3 software. A total of 8 studies, involving 2995 patients with inguinal hernia, were included in the analysis. The meta-analysis results revealed that the TS group had a higher incidence of seroma compared to the RS group [OR = 1.74, 95% CI (1.35, 2.25), P < 0.0001], and a prolonged time to return to normal activity postoperatively [MD = 0.99, 95% CI (0.85, 1.14), P < 0.00001]. However, no statistically significant differences were observed between the two groups in terms of operation time [MD = -1.75, 95% CI (- 8.72, 5.22), P = 0.62], incidence of postoperative pain [OR = 1.00, 95% CI (0.41, 2.44), P = 1.00], overall postoperative complication rate [OR = 0.98, 95% CI (0.43, 2.20), P = 0.95], and recurrence rate fOR = 2.53, 95% CI (0.61, 10.39), P = 0.20]. Transected sac in laparoscopic inguinal hernia repair is associated with an increased incidence of seroma and a longer recovery time for patients to return to normal activity. Clinical trial registration Registration number is INPLASY20223110070.

Clinical characteristics, diagnosis and short-term outcomes of COVID-19-associated acute myocarditis in China.

AIMS: Acute myocarditis (AM) has been recognized as a rare complication of coronavirus disease 2019 (COVID-19) infection. This study was conducted to present the clinical characteristics, disease courses and short-term prognoses of Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induced AM in China, which has been unavailable so far. METHODS AND RESULTS: Data from 28 patients diagnosed with definite COVID-19-associated AM from 6 hospitals in China between 1 December 2022 and 30 June 2023 were collected and analysed. The diagnosis of AM was based on increased troponin level plus typical findings of AM on cardiac magnetic resonance (CMR) imaging and/or endomyocardial biopsy. Among 28 patients with definite COVID-19-related AM, median age was 37 years (Q1-Q3: 22-52) and 53.6% were men. Twenty-three patients occurred within 2 weeks of the onset of COVID-19 infection, 10 patients underwent endomyocardial biopsy and CMR was performed in all patients. Seven (25.0%) patients developed fulminant myocarditis that required inotropic agents or temporary mechanical circulatory support. Of the nine patients (32.1%) with left ventricular ejection fraction (LVEF) below 50% on admission, five had fully recovered LVEF and two demonstrated improvement but to levels below normal at discharge. The comparison of CMR parameters between the baseline and first follow-up showed that ECV was decreased at the first follow-up [28.95 (25.38, 32.55)% vs. 33.65 (31.58, 37.55)%, P = 0.028), while other CMR parameters had no significant changes. Eighteen patients (64.3%) were prescribed with corticosteroids, and seven patients (25.0%) underwent temporary mechanical circulatory support. Only two patients died during hospitalization. CONCLUSIONS: The majority of COVID-19-associated AM occurred within 2 weeks of Omicron variant infection. Fulminant myocarditis complicated by hemodynamic instability requiring temporary mechanical circulatory support was not uncommon. However, short-term outcome was generally good and most AM patients fully recovered.

Astragalus membranaceus and its monomers treat peritoneal fibrosis and related muscle atrophy through the AR/TGF-ß1 pathway.

Background: To anticipate the potential molecular mechanism of Astragalus membranaceus (AM) and its monomer, Calycosin, against peritoneal fibrosis (PF) and related muscle atrophy using mRNA-seq, network pharmacology, and serum pharmacochemistry. Methods: Animal tissues were examined to evaluate a CKD-PF mice model construction. mRNA sequencing was performed to find differential targets. The core target genes of AM against PF were screened through network pharmacology analysis, and CKD-PF mice models were given high- and low-dose AM to verify common genes. Serum pharmacochemistry was conducted to clarify which components of AM can enter the blood circulation, and the selected monomer was further validated through cell experiments for the effect on PF and mesothelial mesenchymal transition (MMT) of peritoneal mesothelial cells (PMCs). Results: The CKD-PF mice models were successfully constructed. A total of 31,184 genes were detected in the blank and CKD-PF groups, and 228 transcription factors had significant differences between the groups. Combined with network pharmacology analysis, a total of 228 AM-PF-related targets were identified. Androgen receptor (AR) was the remarkable transcription factor involved in regulating transforming growth factor-ß1 (TGF-ß1). AM may be involved in regulating the AR/TGF-ß1 signaling pathway and may alleviate peritoneal dialysis-related fibrosis and muscle atrophy in CKD-PF mice. In 3% peritoneal dialysis solution-stimulated HMrSV5 cells, AR expression levels were dramatically reduced, whereas TGF-ß1/p-smads expression levels were considerably increased. Conclusion: AM could ameliorate PF and related muscle atrophy via the co-target AR and modulated AR/TGF-ß1 pathway. Calycosin, a monomer of AM, could partially reverse PMC MMT via the AR/TGF-ß1/smads pathway. This study explored the traditional Chinese medicine theory of "same treatment for different diseases," and supplied the pharmacological evidence of "AM can treat flaccidity syndrome."

Plant-based and planetary-health diets, environmental burden, and risk of mortality: a prospective cohort study of middle-aged and older adults in China.

BACKGROUND: Plant-based diets (PBDs) and planetary-health diets (PHDs) are recommended for their potential health and environmental benefits, but population-based evidence in diverse cultures is scarce. METHODS: We included 9364 adults aged 45 years and older (52·3% female, 47·7% male) from the open cohort of the China Health and Nutrition Survey. Dietary intake was assessed using 3-day 24 h dietary recalls combined with weighing methods from 1997 to 2011, and mortality was documented from 1997 to 2015. We calculated the overall PBD index (PDI), healthful PBD index (hPDI), and unhealthful PBD index (uPDI; ranges 18-90), and the PHD score (range 0-140). We also estimated the related greenhouse gas emissions, land appropriation, and total water footprint and examined their associations with mortality. FINDINGS: PBD indices were inversely related to greenhouse gas emissions, land appropriation, and total water footprint, whereas higher PHD score was related to higher environmental burdens (p<0·0001). During follow-up (mean 9·2 years), 792 (8·5%) death cases were documented. PDI (HR 1·08 [95% CI 0·88-1·32]) and hPDI (0·98 [0·80-1·21]) were not significantly associated with mortality, whereas higher uPDI was related to a higher mortality risk (1·55 [1·26-1·91]). In contrast, higher PHD score was associated with lower mortality risk (0·79 [0·63-0·99]). INTERPRETATION: The PBDs showed environmental benefits, but are not necessarily associated with lower mortality risk. The PHD, developed mainly in western populations, was related to lower mortality risk but higher environmental burdens in the Chinese population. FUNDING: Fundamental Research Funds for the Central Universities, Zhejiang University Global Partnership Fund, and National Natural Science Foundation of China.

Exploring the heart-brain and brain-heart axes: Insights from a bidirectional Mendelian randomization study on brain cortical structure and cardiovascular disease.

INTRODUCTION: The bidirectional relationship between the brain cortex and cardiovascular diseases (CVDs) remains inadequately explored. METHODS: This study used bidirectional Mendelian randomization (MR) analysis to explore the interactions between nine phenotypes associated with hypertension, heart failure, atrial fibrillation (AF), and coronary heart disease (CHD), and brain cortex measurements. These measurements included total surface area (SA), average thickness (TH), and the SA and TH of 34 regions defined by the Desikan-Killiany atlas. The nine traits were obtained from sources such as the UK Biobank and FinnGen, etc., while MRI-derived traits of cortical structure were sourced from the ENIGMA Consortium. The primary estimate was obtained using the inverse-variance weighted approach. A false discovery rate adjustment was applied to the p-values (resulting in q-values) in the analyses of regional cortical structures. RESULTS: A total of 1,260 two-sample MR analyses were conducted. Existing CHD demonstrated an influence on the SA of the banks of the superior temporal sulcus (bankssts) (q=0.018) and the superior frontal lobe (q=0.018), while hypertension was associated with changes in the TH of the lateral occipital region (q=0.02). Regarding the effects of the brain cortex on CVD incidence, total SA was significantly associated with the risk of CHD. Additionally, 16 and 3 regions exhibited significant effects on blood pressure and AF risk, respectively (q<0.05). These regions were primarily located in the frontal, temporal, and cingulate areas, which are associated with cognitive function and mood regulation. CONCLUSION: The detection of cortical changes through MRI could aid in screening for potential neuropsychiatric disorders in individuals with established CVD. Moreover, abnormalities in cortical structure may predict future CVD risk, offering new insights for prevention and treatment strategies.

Clinical phenotypes of heart failure patients with supranormal ejection fraction.

AIMS: Heart failure (HF) with supranormal ejection fraction (HFsnEF) represents a distinct clinical entity characterized by limited treatment options and an unfavourable prognosis. Revealing its phenotypic diversity is crucial for understanding disease mechanism and optimizing patient management. We aim to identify phenotypic subgroups in HFsnEF using unsupervised clustering analysis. METHODS: Consecutive hospitalized patients with a diagnosis of HF and a left ventricular ejection fraction ≥65% at baseline echocardiographic evaluations were included for analysis. We conducted unsupervised hierarchical clustering analysis on principal components (HCPC) to identify HFsnEF phenogroups using mixed data variables including demographics, HF duration, vital signs, anthropometrics, smoking/drinking status, HF aetiology, comorbid diseases, laboratory tests and echocardiographic parameters. We then employed decision tree modelling to identify parameters capable of distinguishing distinct clusters. Clinical outcomes, including all-cause death, cardiovascular (CV) death and CV readmission for different clusters, were examined. RESULTS: Three mutually exclusive clusters were identified from the cohort of 221 HFsnEF patients. Cluster 1 (52.5%) predominantly consisted of patients with valvular heart disease, who had larger cardiac chambers and a higher prevalence of atrial fibrillation/atrial flutter. Cluster 2 (26.2%) primarily comprised older ischaemic patients with a higher prevalence of metabolic comorbidities. Cluster 3 (21.3%) were mainly hypertrophic cardiomyopathy patients. Two clinical variables were identified that could be used to group all HFsnEF patients into one of the clusters; they were HF aetiology and comorbid diabetes. During the median follow-up of 53.4 months, 46 (20.8%) all-cause deaths occurred, among them 39 of CV causes. Seventy (31.7%) patients experienced CV readmissions. Three clusters showed distinct differences in mortality outcomes, with Cluster 1 exhibiting the highest risk of all-cause mortality [Cluster 1 vs. Cluster 2: adjusted hazard ratio (aHR) = 3.32, P = 0.022; Cluster 1 vs. Cluster 3: aHR = 3.81, P = 0.036; Cluster 2 vs. Cluster 3: aHR = 1.15, P = 0.865] and CV mortality (Cluster 1 vs. Cluster 2: aHR = 3.73, P = 0.022; Cluster 1 vs. Cluster 3: aHR = 4.27, P = 0.020; Cluster 2 vs. Cluster 3: aHR = 1.15, P = 0.870). CV readmission risk was comparable among the three clusters (Cluster 1 vs. Cluster 2: aHR = 0.82, P = 0.590; Cluster 1 vs. Cluster 3: aHR = 1.04, P = 0.900; Cluster 2 vs. Cluster 3: aHR = 1.28, P = 0.580). CONCLUSIONS: In a heterogeneous HFsnEF cohort, three clusters were identified by unsupervised HCPC with distinct clinical characteristics and outcomes.

Astragalus polysaccharides augment BMSC homing via SDF-1/CXCR4 modulation: a novel approach to counteract peritoneal mesenchymal transformation and fibrosis.

PURPOSE: This study aimed to evaluate the potential of astragalus polysaccharide (APS) pretreatment in enhancing the homing and anti-peritoneal fibrosis capabilities of bone marrow mesenchymal stromal cells (BMSCs) and to elucidate the underlying mechanisms. METHODS: Forty male Sprague-Dawley rats were allocated into four groups: control, peritoneal dialysis fluid (PDF), PDF + BMSCs, and PDF + APSBMSCs (APS-pre-treated BMSCs). A peritoneal fibrosis model was induced using PDF. Dil-labeled BMSCs were administered intravenously. Post-transplantation, BMSC homing to the peritoneum and pathological alterations were assessed. Stromal cell-derived factor-1 (SDF-1) levels were quantified via enzyme-linked immunosorbent assay (ELISA), while CXCR4 expression in BMSCs was determined using PCR and immunofluorescence. Additionally, a co-culture system involving BMSCs and peritoneal mesothelial cells (PMCs) was established using a Transwell setup to examine the in vitro effects of APS on BMSC migration and therapeutic efficacy, with the CXCR4 inhibitor AMD3100 deployed to dissect the role of the SDF-1/CXCR4 axis and its downstream impacts. RESULTS: In vivo and in vitro experiments confirmed that APS pre-treatment notably facilitated the targeted homing of BMSCs to the peritoneal tissue of PDF-treated rats, thereby amplifying their therapeutic impact. PDF exposure markedly increased SDF-1 levels in peritoneal and serum samples, which encouraged the migration of CXCR4-positive BMSCs. Inhibition of the SDF-1/CXCR4 axis through AMD3100 application diminished BMSC migration, consequently attenuating their therapeutic response to peritoneal mesenchyme-to-mesothelial transition (MMT). Furthermore, APS upregulated CXCR4 expression in BMSCs, intensified the activation of the SDF-1/CXCR4 axis's downstream pathways, and partially reversed the AMD3100-induced effects. CONCLUSION: APS augments the SDF-1/CXCR4 axis's downstream pathway activation by increasing CXCR4 expression in BMSCs. This action bolsters the targeted homing of BMSCs to the peritoneal tissue and amplifies their suppressive influence on MMT, thereby improving peritoneal fibrosis.

Associations of vegetable and fruit intake with cognitive function and its decline: Two longitudinal studies.

OBJECTIVES: Previous studies suggested protective associations of vegetables and fruits (VF) intake with cognitive function, but evidence on specific types of VF was insufficient. METHODS: The current study included 4066 participants from 1997 to 2006 in the China Health and Nutrition Survey (CHNS) and 6170 participants from 2013 to 2020 in the Health and Retirement Study (HRS). Dietary intake (using 3-day 24-h dietary recalls in CHNS and food frequency questionnaire in HRS) and cognitive function (using the Telephone Interview for Cognitive Status-Modified, TICS-m) were measured. Linear mixed-effects models were used to estimate the beta coefficients (ß) and the 95% confidence intervals (CI) to evaluate the association of VF with cognitive function (z-score) and its decline. RESULTS: Highest intake of total VF was associated with better cognitive function and slower cognitive decline. Differences in cognitive function z-score between the highest and lowest tertiles of VF consumption were 0.039 (95% CI: 0.002, 0.076) for CHNS and 0.063 (95% CI: 0.026, 0.100) for HRS. The corresponding differences in annual cognitive decline were 0.011 (95% CI: 0.002, 0.021) and 0.012 (95% CI: 0.003, 0.020) units respectively. Vegetables and fruits showed independent associations with cognitive function and its decline. In specific VF subgroups, when comparing the highest to the lowest tertile intake, cruciferous vegetables (ß = 0.058, 95% CI: 0.017, 0.100 in CHNS and ß = 0.067, 95% CI: 0.032, 0.101 in HRS) and green leafy vegetables (ß = 0.036, 95% CI: -0.001, 0.073 in CHNS and ß = 0.082, 95% CI: 0.046, 0.117 in HRS) was associated with better cognitive function in both cohorts. Similarly, higher intake of dark-colored vegetables (ß = 0.019, 95% CI: 0.008, 0.030 for red/yellow vegetables in CHNS and ß = 0.004, 95% CI: 0.001, 0.007 for green leafy vegetables in HRS) were associated with slower cognitive decline in subsequent years. Moreover, rigorous sensitivity analyses confirmed the stability of the results. CONCLUSIONS: Our findings support the potential beneficial roles of VF, especially cruciferous vegetables, green leafy vegetables, and red/yellow vegetables, in maintaining cognitive function and slowing cognitive decline in middle-aged and older adults.

Comprehensively evaluating the relationships between marital status and other family factors with cardiovascular disease and long-term overall mortality in the elderly: a study of 48 510 Chinese individuals.

BACKGROUND: Marital status is associated with cardiovascular disease (CVD) incidence and overall mortality, yet limited research on this topic in elderly individuals is available. Our aim was to comprehensively assess the impact of marital status and other family factors on CVD incidence and long-term mortality among elderly people. METHODS: Data from the Chinese Longitudinal Healthy Longevity Survey (2002/2005/2008-2018) for participants aged ≥60 years were analysed. A cross-sectional study initially examined the correlation between spouses, offspring, living arrangements, and CVD using logistic regression. Subsequently, a retrospective cohort study investigated the long-term associations of these factors with overall mortality via Kaplan-Meier and Cox regression analyses. RESULTS: The study involved 48 510 subjects (average age: 87 years). The cross-sectional analysis revealed a correlation between living with a spouse and an increased incidence of heart disease (adjusted OR 1.27, 95% CI 1.04-1.55) and cerebrovascular disease/stroke (adjusted OR 1.26, 95% CI 1.11-1.42). According to the retrospective cohort analysis, living with a spouse significantly reduced overall mortality (adjusted HR 0.84, 95% CI 0.80-0.87), irrespective of marital relationship quality. Conversely, living with offspring (adjusted HR 1.12, 95% CI 1.08-1.16), having more children (adjusted Pnonlinearity = 0.427) or cohabitants (adjusted Pnonlinearity < 0.0001) were associated with increased overall mortality. CONCLUSION: In the elderly population, being married and living with a spouse were not significantly associated with a decrease in CVD incidence but were associated with a reduction in long-term overall mortality. Living with offspring, having more children, or having a larger family size did not replicate the protective effect but indicated greater overall mortality.

Development and clinical validation of a dual ddPCR assay for detecting carbapenem-resistant Acinetobacter baumannii in bloodstream infections.

Objective: Acinetobacter baumannii (A. baumannii, AB) represents a major species of Gram-negative bacteria involved in bloodstream infections (BSIs) and shows a high capability of developing antibiotic resistance. Especially, carbapenem-resistant Acinetobacter baumannii (CRAB) becomes more and more prevalent in BSIs. Hence, a rapid and sensitive CRAB detection method is of urgent need to reduce the morbidity and mortality due to CRAB-associated BSIs. Methods: A dual droplet digital PCR (ddPCR) reaction system was designed for detecting the antibiotic resistance gene OXA-23 and AB-specific gene gltA. Then, the specificity of the primers and probes, limit of detection (LOD), linear range, and accuracy of the assay were evaluated. Furthermore, the established assay approach was validated on 37 clinical isolates and compared with blood culture and drug sensitivity tests. Results: The dual ddPCR method established in this study demonstrated strong primer and probe specificity, distinguishing CRAB among 21 common clinical pathogens. The method showed excellent precision (3 × 10-4 ng/µL, CV < 25%) and linearity (OXA-23: y = 1.4558x + 4.0981, R2 = 0.9976; gltA: y = 1.2716x + 3.6092, R2 = 0.9949). While the dual qPCR LOD is 3 × 10-3 ng/µL, the dual ddPCR's LOD stands at 3 × 10-4 ng/µL, indicating a higher sensitivity in the latter. When applied to detect 35 patients with BSIs of AB, the results were consistent with clinical blood culture identification and drug sensitivity tests. Conclusion: The dual ddPCR detection method for OXA-23 and gltA developed in this study exhibits good specificity, excellent linearity, and a higher LOD than qPCR. It demonstrates reproducibility even for minute samples, making it suitable for rapid diagnosis and precision treatment of CRAB in BSIs.

The Association of Allergy-Related and Non-Allergy-Related Olfactory Impairment with Cognitive Function in Older Adults: Two Cross- Sectional Studies.

BACKGROUND: Evidence on the association of Olfactory Impairment (OI) with age-related cognitive decline is inconclusive, and the potential influence of allergy remains unclear. OBJECTIVE: We aimed to evaluate the cross-sectional associations of allergy-related and non-allergy- related OI to cognitive function. METHODS: We included 2,499 participants from the Health and Retirement Study (HRS)-Harmonized Cognitive Assessment Protocol (HCAP) sub-study and 1,086 participants from the English Longitudinal Study of Ageing (ELSA)-HCAP. The Olfactory Function Field Exam (OFFE) using Sniffin' Stick odor pens was used to objectively assess olfactory function and an olfactory score <6/11 indicated OI. Mini-Mental Status Examination (MMSE) was used to assess global cognitive function and define cognitive impairment (<24/30). A neuropsychologic battery was used to assess five cognitive domains. RESULTS: Compared to non-OI participants, individuals with OI had lower MMSE z-score [ßHRS = -0.33, 95% Confidence Interval (CI): -0.41 to -0.24; ßELSA = -0.31, -0.43 to -0.18] and higher prevalence of cognitive impairment (Prevalence Ratio (PR)HRS = 1.46, 1.06 to 2.01; PRELSA = 1.63, 1.26 to 2.11). The associations were stronger for non-allergy-related OI (ßHRS = -0.36; ßELSA = -0.34) than for allergy-related OI (ßHRS = -0.26; ßELSA = 0.13). Similar associations were observed with domain- specific cognitive function measures. CONCLUSION: OI, particularly non-allergy-related OI, was related to poorer cognitive function in older adults. Although the current cross-sectional study is subject to several limitations, such as reverse causality and residual confounding, the findings will provide insights into the OI-cognition association and enlighten future attention to non-allergy-related OI for the prevention of potential cognitive impairment.

Intercellular communication in peritoneal dialysis.

Long-term peritoneal dialysis (PD) causes structural and functional alterations of the peritoneal membrane. Peritoneal deterioration and fibrosis are multicellular and multimolecular processes. Under stimulation by deleterious factors such as non-biocompatibility of PD solution, various cells in the abdominal cavity show differing characteristics, such as the secretion of different cytokines, varying protein expression levels, and transdifferentiation into other cells. In this review, we discuss the role of various cells in the abdominal cavity and their interactions in the pathogenesis of PD. An in-depth understanding of intercellular communication and inter-organ communication in PD will lead to a better understanding of the pathogenesis of this disease, enabling the development of novel therapeutic targets.

Validity of food and nutrient intakes assessed by a food frequency questionnaire among Chinese adults.

BACKGROUND: Studies regarding the validity of the food frequency questionnaire (FFQ) and the food composition table (FCT) are limited in Asian countries. We aimed to evaluate the validity of a 64-item FFQ and different methods of constructing the FFQ FCTs for assessing dietary intakes of foods and nutrients among adults in eastern China. METHODS: A total of 2325 participants (aged 56.2 ± 14.9 years, 51.6% female) from nine cities in Zhejiang province who completed a 64-item FFQ and 3-day 24-hour dietary recalls (24HRs) in 2015 were included. Eight FFQ FCTs were generated covering food items and specific weights estimated using professional knowledge, representative 24HRs data, or the Chinese FCT (CFCT). Energy-adjusted intakes of foods and nutrients were estimated by residual and energy density methods. Spearman correlation coefficients (SCCs) of intakes of 14 food groups and 17 nutrients between FFQ and 24HRs were calculated to evaluate the overall validity of FFQ. RESULTS: The average intakes of most food groups and nutrients assessed with FFQ were higher than those assessed using the 24HRs. For the food groups, the averaged energy-adjusted (residual method) SCC between FFQ and 24HRs was 0.27, ranging from 0.14 (starch-rich beans) to 0.49 (aquatic products). For nutrient assessment, the weighted FCT (WFCT) performs the best, and the averaged energy-adjusted (residual method) SCC was 0.26, ranging from 0.16 (iron) to 0.37 (potassium). Similar correlations with 24HRs were observed when using other FFQ FCT in the calculation of nutrient intakes. CONCLUSION: The 64-item Chinese FFQ and the WFCT were reasonably valid to assess the dietary intakes of certain foods and nutrients among adults in eastern China.

Catalyst-free late-stage functionalization to assemble α-acyloxyenamide electrophiles for selectively profiling conserved lysine residues.

Covalent probes coupled with chemical proteomics represent a powerful method for investigating small molecule and protein interactions. However, the creation of a reactive warhead within various ligands to form covalent probes has been a major obstacle. Herein, we report a convenient and robust process to assemble a unique electrophile, an α-acyloxyenamide, through a one-step late-stage coupling reaction. This procedure demonstrates remarkable tolerance towards other functional groups and facilitates ligand-directed labeling in proteins of interest. The reactive group has been successfully incorporated into a clinical drug targeting the EGFR L858R mutant, erlotinib, and a pan-kinase inhibitor. The resulting probes have been shown to be able to covalently engage a lysine residue proximal to the ATP-binding pocket of the EGFR L858R mutant. A series of active sites, and Mg2+, ATP-binding sites of kinases, such as K33 of CDK1, CDK2, CDK5 were detected. This is the first report of engaging these conserved catalytic lysine residues in kinases with covalent inhibition. Further application of this methodology to natural products has demonstrated its success in profiling ligandable conserved lysine residues in whole proteome. These findings offer insights for the development of new targeted covalent inhibitors (TCIs).

Renal function modifies the association between hemoconcentration and outcomes in hospitalized heart failure patients.

Evidence-based management of decongestion is lacking in hospitalized heart failure (HHF) patients, especially in patients with impaired renal function. Hemoconcentration is an objective measure of decongestion that portends a favorable prognosis and guides management in HHF patients with preserved renal function. We aim to investigate whether it remains a prognosticator in patients with renal impairment, and to refine the identification of subpopulations who will benefit from hemoconcentration-guided therapy. HHF patients admitted to Heart Failure Center of Fuwai Hospital were consecutively included from December 2006 to June 2018. Patient characteristics were depicted. Relationships between in-hospital hemoconcentration, worsening renal function (WRF), and one-year all-cause mortality were investigated in the total population and compared between renal function groups using survival analysis and cubic splines, with a special focus on renal function-based interactions. The association was further validated in sensitivity analyses. Clinically relevant cut-offs and subpopulations were identified by subpopulation treatment effect pattern plots (STEPP) and subgroup analysis. 3661 participants (30.4% with impaired renal function) were included. Hemoconcentration, reflected by an in-hospital increase in hemoglobin, hematocrit, or a relative reduction in estimated plasma volume from baseline to discharge, was predictive of decreased one-year mortality in the total cohort despite its correlation with higher WRF incidence. The prognostic value of hemoconcentration differed in patients with impaired and preserved renal function. Hemoconcentration was related to a favorable prognosis in patients with preserved renal function (HR, 0.69; 95% CI, 0.53-0.90; P = 0.007), especially in young male patients with New York Heart Association functional class III-IV, reduced ejection fraction, and baseline eGFR > 75 mL/min/1.73m2. Contrarily, impaired renal function patients experienced a higher incidence of WRF, and hemoconcentration was no longer related to outcome (HR, 0.90; 95% CI, 0.64-1.26; P = 0.545), with findings consistent in all clinically relevant subgroups. In HHF patients, the prognostic value of hemoconcentration differs by renal function, and the clinical utility of hemoconcentration is contingent on preserved renal function.

Dietary factors in relation to the risk of cognitive impairment and physical frailty in Chinese older adults: a prospective cohort study.

PURPOSE: The study aimed to investigate the independent associations of dietary factors with cognitive impairment (CI) and physical frailty (PF) among Chinese older adults. METHODS: This study included 10,734 participants (mean age = 78.7 years) free of CI and PF at baseline from the Chinese Longitudinal Health Longevity Survey. Dietary intake was collected using a simplified food frequency questionnaire every 3-4 years. The Chinese version Mini-Mental State Examination was used to assess cognition function, participants with a score below 18 were defined as CI. PF was defined using the activities of daily living, instrumental activities of daily living, and functional limitation-related questions. The outcome was defined as the first onset of either CI or PF. Competing risk models were used to estimate the corresponding hazard ratios (HRs) and the 95% confidence intervals (95% CIs). RESULTS: During the study follow-up (mean = 8.1 years), a total of 1220 CI cases and 1451 PF cases were newly identified. Higher frequency of fruits intake was associated with a lower hazard of CI (HR = 0.75, 95% CI 0.58-0.97), whereas higher intake of preserved vegetables demonstrated an opposite association (HR = 1.23, 95% CI 1.07-1.42). In terms of PF, we observed a lower risk associated with higher meat and poultry intake (HR = 0.72, 95% CI 0.61-0.88). In particular, a significant protective association of fish and aquatic products intake with PF was observed among participants with ≥ 28 natural teeth (HR = 0.52, 95% CI 0.27-0.99). CONCLUSION: Our findings suggest divergent roles of major dietary factors in the development of CI and PF among Chinese older adults.

Sex differences in the associations between relative fat mass and all-cause and cardiovascular mortality: A population-based prospective cohort study.

BACKGROUND AND AIMS: The novel sex-specific anthropometric equation relative fat mass (RFM) is a new estimator of whole-body fat %. The study aimed to investigate the predictive role of RFM in cardiometabolic abnormalities, cardiovascular disease (CVD), all-cause and cardiovascular mortality, and explored potential sex differences. METHODS AND RESULTS: The study analyzed data from 26,754 adults in NHANES 1999-2010, with a median follow-up of 13.8 years. The correlation between RFM and body composition as well as fat distribution assessed by dual-energy X-ray absorptiometry was investigated. Weighted multivariable generalized linear models, Cox proportional hazards models and restricted cubic spline were applied to investigate the predictive role of RFM in metabolic markers, cardiovascular risk factors, CVD, all-cause and cardiovascular mortality. RFM exhibited a robust correlation with both whole-body fat % and trunk fat %. Higher RFM exhibited a stronger association with impaired glucose homeostasis, serum lipids, the incidence of hypertension, and coronary heart disease in males, while a stronger association with C-reactive protein in females. A U-shaped association between RFM and all-cause mortality was observed only in males. The hazard ratio (HR) of all-cause and cardiovascular mortality in males increased rapidly when RFM exceeded 30. However, in females, the HR of all-cause and cardiovascular mortality fluctuated until RFM exceeded 45, after which it increased rapidly. CONCLUSION: RFM was a sex-specific estimator for both general and central obesity, sex-specific differences in predicting cardiometabolic abnormalities and adverse events using RFM might be partially attributed to differences in body composition and fat distribution between sexes.

Clinicopathologic characteristics, treatment, prognosis and pregnancy outcomes in rhabdomyosarcoma of the uterine cervix: a case series.

OBJECTIVES: In this retrospective observational study, cases from our institution were included and the published literature reviewed to investigate the diagnosis and prognosis of cervical rhabdomyosarcoma, a rare group of tumours. MATERIAL AND METHODS: The clinicopathological data of 12 patients with cervical rhabdomyosarcoma (RMS) treated at the West China Second University Hospital of Sichuan University from January 2006 to May 2023 were collected, and their clinicopathological characteristics, diagnoses, treatments, prognoses and pregnancy outcomes were retrospectively analysed. RESULTS: (1) Clinical characteristics: The ages of the 12 RMS patients ranged from 15 to 50 years, with a median age of 17 years. Five of the patients were adults, and seven were adolescents. The initial symptoms were vaginal bleeding in 5 patients, vaginal tissue prolapse in 6 patients, and abdominal pain and urinary frequency in 1 patient. Two patients were considered to have "cervical polyps" and underwent polypectomy at the other hospitals, but the cervical mass recurred soon thereafter. (2) Pathological features: The maximum tumour diameter ranged from 3 to 25 cm. The twelve cases of cervical RMS consisted of embryonal rhabdomyosarcoma (ERMS) in 7 adolescents, ERMS in 3 adults, and pleomorphic rhabdomyosarcoma (PRMS) in 2 adults. Immunohistochemical results showed the expression of one or more characteristic markers of RMS. We reclassified tumour stage according to the Intergroup Rhabdomyosarcoma Study (IRS) clinical group and tumour node metastasis (TNM) classification. (3) Treatment: Eight patients underwent radical surgery (66.7%, 8/12), including all 5 of the included adults and 3 of the adolescents, 2 of whom were treated 10 years ago. Conservative surgical resection was performed on four patients (33.3%, 4/12), all of whom were adolescents. Postoperative chemotherapy was given to all patients except one, but one patient who underwent radical surgery discontinued chemotherapy on her own without receiving a full course. Two of the ERMS patients underwent preoperative chemotherapy, and the lesions were significantly reduced. (4) Prognosis: One of the 12 patients with cervical RMS was lost to follow-up. Of the remaining 11 patients, 10 (including seven adolescents and three adults) survived tumour free (90.9%, 10/11), and 1 adult patient with existing pulmonary multiple metastases (IRS stage IV, T2N0M1) at the initial diagnosis survived 9 months with progression-free disease (9.1%, 1/11). The median survival time was 91 months (5 to 213 months). Among 4 patients receiving fertility-sparing management, 1 conceived and delivered successfully (25%). CONCLUSIONS: The treatment of cervical RMS must take the patient's age and reproductive intent into account. The overall prognosis for cervical RMS in children and adolescents is good, and conservative surgical resection combined with chemotherapy is recommended to preserve fertility. The pregnancy outcome is also worth anticipating. For patients who have completed childbirth, radical surgery is preferred. Approaches to accurately assessing the patient's condition, grasping the indications and scope of surgery, and developing chemoradiotherapy regimens deserve further exploration.

sST2 and Big ET-1 as Alternatives of Multi-Biomarkers Strategies for Prognosis Evaluation in Patients Hospitalized with Heart Failure.

Objective: To identify biomarkers with independent prognostic value and investigate the prognostic value of multiple biomarkers in combination in patients hospitalized with heart failure. Methods: A total of 884 consecutive patients hospitalized with heart failure from 2015 to 2017 were enrolled. Twelve biomarkers were measured on admission, and the relationships between biomarkers and outcomes were assessed. Results: During the median follow-up of 913 days, 291 patients (32.9%) suffered from primary endpoint events. Soluble suppression of tumorigenicity-2 (sST2) (per log [unit] increase, adjusted HR [95% CI]: 1.39 [1.13,1.72], P = 0.002) and big endothelin-1 (big ET-1) (per log [unit] increase, adjusted HR [95% CI]: 1.56 [1.23,1.97], P < 0.001) remained independent predictors of primary endpoint event after adjusting for other predictors including N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT). Both sST2 (C-statistic: 0.810 vs 0.801, P = 0.005, and 0.832 vs 0.826, P = 0.024, respectively) and big ET-1 (C-statistic: 0.829 vs 0.801, P = 0.001, and 0.843 vs 0.826, P < 0.001, respectively) significantly improved the predictive value for primary endpoint event at 1 year and 3 years. However, only big ET-1 (C-statistic: 0.852 vs 0.846, P = 0.014) significantly improved the predictive value at 3 months when added to clinical predictors and known biomarkers. According to the number of elevated biomarkers (including NT-proBNP, hs-cTnT, sST2, and big ET-1), patients with three or more elevated biomarkers had a higher risk of primary endpoint event compared to those with two elevated biomarkers (P = 0.001), as well as in patients with two elevated biomarkers compared to those with one elevated biomarker (P = 0.004). However, the risk of primary endpoint event was comparable between patients with one elevated biomarker and those with no elevated biomarker (P = 0.582). Conclusion: Multiple biomarkers in combination could provide a better prognostic value than a single biomarker. sST2 and big ET-1 could act as alternatives of multi-biomarkers strategies for prognosis evaluation beyond NT-proBNP and hs-cTnT in patients hospitalized with heart failure.