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Abstract Background Early-life cardiovascular risk factors (CVRFs) are known to be associated with target organ damage during adolescence and premature cardiovascular morbidity and mortality during adulthood. However, contemporary data describing whether the prevalence of CVRFs and treatment and control rates have changed are limited. This study aimed to examine the temporal trends in the prevalence, treatment, and control of CVRFs among US adolescents over the past 2 decades. Methods This is a serial cross-sectional study using data from nine National Health and Nutrition Examination Survey cycles (January 2001—March 2020). US adolescents (aged 12 to 19 years) with information regarding CVRFs (including hypertension, elevated blood pressure [BP], diabetes, prediabetes, hyperlipidemia, obesity, overweight, cigarette use, inactive physical activity, and poor diet quality) were included. Age-adjusted trends in CVRF prevalence, treatment, and control were examined. Joinpoint regression analysis was performed to estimate changes in the prevalence, treatment, and control over time. The variation by sociodemographic characteristics were also described. Results A total of 15,155 US adolescents aged 12 to 19 years (representing ≈ 32.4 million people) were included. From 2001 to March 2020, there was an increase in the prevalence of prediabetes (from 12.5% [95% confidence interval (CI), 10.2%-14.9%] to 37.6% [95% CI, 29.1%-46.2%]) and overweight/obesity (from 21.1% [95% CI, 19.3%-22.8%] to 24.8% [95% CI, 21.4%-28.2%]; from 16.0% [95% CI, 14.1%-17.9%] to 20.3% [95% CI, 17.9%-22.7%]; respectively), no improvement in the prevalence of elevated BP (from 10.4% [95% CI, 8.9%-11.8%] to 11.0% [95% CI, 8.7%-13.4%]), diabetes (from 0.7% [95% CI, 0.2%-1.2%] to 1.2% [95% CI, 0.3%-2.2%]), and poor diet quality (from 76.1% [95% CI, 74.0%-78.2%] to 71.7% [95% CI, 68.5%-74.9%]), and a decrease in the prevalence of hypertension (from 8.1% [95% CI, 6.9%-9.4%] to 5.5% [95% CI, 3.7%-7.3%]), hyperlipidemia (from 34.2% [95% CI, 30.9%-37.5%] to 22.8% [95% CI, 18.7%-26.8%]), cigarette use (from 18.0% [95% CI, 15.7%-20.3%] to 3.5% [95% CI, 2.0%-5.0%]), and inactive physical activity (from 83.0% [95% CI, 80.7%-85.3%] to 9.5% [95% CI, 4.2%-14.8%]). Sex and race/ethnicity affected the evolution of CVRF prevalence differently. Whilst treatment rates for hypertension and diabetes did not improve significantly (from 9.6% [95% CI, 3.5%-15.8%] to 6.0% [95% CI, 1.4%-10.6%]; from 51.0% [95% CI, 23.3%-78.7%] to 26.5% [95% CI, 0.0%-54.7%]; respectively), BP control was relatively stable (from 75.7% [95% CI, 56.8%-94.7%] to 73.5% [95% CI, 40.3%-100.0%]), while glycemic control improved to a certain extent, although it remained suboptimal (from 11.8% [95% CI, 0.0%-31.5%] to 62.7% [95% CI, 62.7%-62.7%]). Conclusions From 2001 to March 2020, although prediabetes and overweight/obesity increased, hypertension, hyperlipidemia, cigarette use, and inactive physical activity decreased among US adolescents aged 12 to 19 years, whereas elevated BP, diabetes, and poor diet quality remained unchanged. There were disparities in CVRF prevalence and trends across sociodemographic subpopulations. While treatment and control rates for hypertension and diabetes plateaued, BP control were stable, and improved glycemic control was observed.

Abstract Effective therapeutic targets and early diagnosis are major challenges in the treatment of gastrointestinal tract (GIT) cancers. SALL4 is a well-known transcription factor that is involved in organogenesis during embryonic development. Previous studies have revealed that SALL4 regulates cell proliferation, survival, and migration and maintains stem cell function in mature cells. Additionally, SALL4 overexpression is associated with tumorigenesis. Despite its characterization as a biomarker in various cancers, the role of SALL4 in GIT cancers and the underlying mechanisms are unclear. We describe the functions of SALL4 in GIT cancers and discuss its upstream/downstream genes and pathways associated with each cancer. We also consider the possibility of targeting these genes or pathways as potential therapeutic options for GIT cancers.

Abstract It is a great challenge to discover novel chemical reactions suitable for biological analysis in a living system. The development of novel protein thiol blocking agents is a crucial need for exploring protein thiol functions in protein refolding, signal transduction, and redox regulation. We are always keen on seeking novel chemical reactions applied to endogenous biological macromolecules or protein thiol sensing, blocking, and labeling. In the present work, we have successfully developed a novel agent to block protein thiol by enhanced electron‐withdrawing inductive effects. This sensing and blocking process was detailedly monitored by UV‐vis, fluorescent spectra, and SDS‐Page gel separation. The spectral studies demonstrated that the agent could react ultrafastly with thiol within seconds at μM level. Furthermore, fluorescent imaging in cells and in vivo was further used for the validation of its ability to sensing and blocking thiol, providing evidence of downregulated protein thiols in Parkinson's disease. The enhanced electron‐withdrawing inductive effect strategy in this work may provide a general guideline for designing protein thiol agent.

In this study, ozone catalysts (hydrogenation-modified red mud, HM-RM) successfully prepared by hydrogenation-modification of industrial hazardous solid waste red mud (RM) as a raw material in accordance with the viewpoint of treating waste with waste and using waste. Meanwhile, as for the common phenomenon of membrane fouling, uneven distribution of multiphase solid catalysts and ozone in liquids, the addition of ultrasound can not only disperse materials, but also play a role in online cleaning of ceramic membranes and catalysts. The optimum treatment conditions for Rhodamine B (RhB) solution with volume of 2 L and concentration of 40 mg/L were catalyst concentration of 0.4 mg/L, reaction temperature of 45 °C, ultrasonic time of 1 h, ultrasonic intensity of 600 W, removal rate of RhB was up to 90 %. In addition, the computational fluid dynamics (CFD) simulation method was used to investigate the fluid flow between the two gas-liquid phases and the effect of the negative pressure of the membrane pump on the fluid by the analysis of flow, pressure and ozone flux of the ceramic membrane(CM) reaction apparatus. The CFD simulation results showed that at the inlet gas-liquid flow rate of 3 m/s and the negative pressure of 20,000 Pa, the maximum flow rates of CM-1 were 3 m/s, 0.752 m/s for CM-2, and 0.228 m/s for CM-3, respectively. Vortices, which are beneficial to solid-liquid mixing and gas-liquid mass transfer, formed between the suction port CM-1 of CM-1 and the inlets of CM-2 and CM-3. This discovery is consistent with relevant experimental research results. Significantly higher concentrations of both •OH and dissolved ozone were observed in the US/HM-RM/O3 system compared to other systems, indicating the significant improvement in ozone utilization rate through the application of ultrasound. The superiority of the US/HM-RM/O3 device was demonstrated. The real dye effluent was tested under optimum operating conditions and the results showed that COD and TOC were reduced by 81.34 % and 60.23 % respectively after 180 min of treatment. The above research can provide technical support for the treatment of dye wastewater using Ultrasound-enhanced ozone oxidation ceramic membranes.

Abstract Background The influence of sarcopenic obesity (SO) on overall survival in older adults with hypertension has not been addressed. The aim of this study was to investigate the prevalence and mortality predictive value of various body composition phenotypes, focusing mainly on SO, in older adults with hypertension. Methods We included 1105 hypertensive patients aged ≥ 60 years from the National Health and Nutrition Examination Survey 1999–2004. Sarcopenia was broadly defined based on low lean mass (LLM; as measured by dual-energy X-ray absorptiometry), and was defined using appendicular lean mass (ALM) divided by height squared (ALM/height2), weight (ALM/weight), and body mass index (BMI; ALM/BMI), respectively. Obesity was defined as BMI ≥ 30 kg/m2, body fat percentage ≥ 30/42%, or waist circumference ≥ 102/88 cm. The prevalence of LLM with obesity was estimated according to each ALM index (ALMI). Multivariable Cox regression analysis and sensitivity analysis were used to examine the association between various body composition phenotypes and all-cause mortality. Results In older adults with hypertension, the prevalence of LLM with obesity by the ALM/height2 index (9.8%) was lower relative to the ALM/weight (11.7%) and ALM/BMI indexes (19.6%). After a median follow-up of 15.4 years, 642 deaths occurred. In the fully adjusted models, LLM with obesity was significantly associated with a higher risk of all-cause mortality (hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.14–2.49, P = 0.008; HR 1.48, 95% CI 1.04–2.10, P = 0.028; HR 1.30, 95% CI 1.02–1.66, P = 0.037; respectively) compared with the normal body phenotype, with no statistical differences found in individuals with LLM or obesity alone. Sensitivity analysis confirmed the robustness of the results. Conclusions The prevalence of LLM with obesity markedly differed in older adults with hypertension according to the 3 different ALMIs, varying from 9.8%, 11.7%, to 19.6%. Patients with both LLM and obesity had a higher risk of all-cause mortality. Further large, prospective, cohort studies are warranted to validate these findings and uncover underlying mechanisms.

Abstract Aims The early identification and appropriate management may provide clinically meaningful and substained benefits in patients with acute heart failure (AHF). This study aimed to develop an integrative nomogram with myocardial perfusion imaging (MPI) for predicting the risk of all‐cause mortality in AHF patients. Methods and results Prospective study of 147 patients with AHF who received gated MPI (59.0 [47.5, 68.0] years; 78.2% males) were enrolled and followed for the primary endpoint of all‐cause mortality. We analysed the demographic information, laboratory tests, electrocardiogram, and transthoracic echocardiogram by the least absolute shrinkage and selection operator (LASSO) regression for selection of key features. A multivariate stepwise Cox analysis was performed to identify independent risk factors and construct a nomogram. The predictive values of the constructed model were compared by Kaplan–Meier curve, area under the curves (AUCs), calibration plots, continuous net reclassification improvement, integrated discrimination improvement, and decision curve analysis. The 1, 3, and 5 year cumulative rates of death were 10%, 22%, and 29%, respectively. Diastolic blood pressure [hazard ratio (HR) 0.96, 95% confidence interval (CI) 0.93–0.99; P = 0.017], valvular heart disease (HR 3.05, 95% CI 1.36–6.83; P = 0.007), cardiac resynchronization therapy (HR 0.37, 95% CI 0.17–0.82; P = 0.014), N‐terminal pro‐B‐type natriuretic peptide (per 100 pg/mL; HR 1.02, 95% CI 1.01–1.03; P

Background: This study explores the relationship between waist circumference and morbidity of cardiovascular diseases (CVD) and all-cause mortality in metabolically healthy individuals. Methods: A cohort of 5775 metabolically healthy participants from the 2001–2014 US National Health and Nutrition Examination Survey and National Death Index database was tracked over a median period of 81 months. These participants were divided into quartiles (Q1, Q2, Q3, Q4) based on increasing waist circumference. To compensate for missing covariates, multivariate multiple imputation methods were used. Adjusted logistic regression models were employed to examine the correlation between waist circumference and cardiovascular disease prevalence. Furthermore, Kaplan-Meier curves and multivariable Cox regression analysis were utilized to evaluate the association between waist circumference and all-cause mortality, both qualitatively and quantitatively. Results: The adjusted logistic regression model indicated that a 10 cm increase in waist circumference was associated with a 1.45 times higher prevalence of CVD. As a categorical variable, there was a significant upward trend in CVD incidence across quartiles of waist circumference. The adjusted odds ratios (95% confidence intervals) were 2.41 (1.13–5.53) for Q2, 2.65 (1.18–6.39) for Q3, and 2.53 (0.9–7.44) for Q4, compared to Q1. Notably, individuals with high waist circumference showed significantly poorer survival compared to those with low waist circumference (p = 0.008). The Cox regression analysis revealed that each 10 cm increase in waist circumference contributed to an ~8% increase in all-cause mortality. Conclusions: This study underscores a positive correlation between waist circumference and both CVD morbidity and all-cause mortality in metabolically healthy individuals. The findings highlight the significance of routinely monitoring waist circumference for effective CVD risk management, regardless of metabolic health status.

Abstract Spectrum matching is the most common method for compound identification in mass spectrometry (MS). However, some challenges limit its efficiency, including the coverage of spectral libraries, the accuracy, and the speed of matching. In this study, a million-scale in-silico EI-MS library is established. Furthermore, an ultra-fast and accurate spectrum matching (FastEI) method is proposed to substantially improve accuracy using Word2vec spectral embedding and boost the speed using the hierarchical navigable small-world graph (HNSW). It achieves 80.4% recall@10 accuracy (88.3% with 5 Da mass filter) with a speedup of two orders of magnitude compared with the weighted cosine similarity method (WCS). When FastEI is applied to identify the molecules beyond NIST 2017 library, it achieves 50% recall@1 accuracy. FastEI is packaged as a standalone and user-friendly software for common users with limited computational backgrounds. Overall, FastEI combined with a million-scale in-silico library facilitates compound identification as an accurate and ultra-fast tool.

To achieve an adjustable setting time and significantly improved early strength of a new type of sulphoaluminate cement-based double-liquid grouting material (SACDL), the effects of calcium formate, sodium sulfate, lithium carbonate, and a composite early strength agent on the setting hardening and early hydration behavior of SACDL paste were studied by means of setting time, fluidity, compressive strength, and viscosity tests. The results showed that the adsorption and osmosis of calcium formate, the complex decomposition of sodium sulfate, the precipitation polarization of lithium carbonate and the synergistic action of the composite early strength agent could accelerate the early hydration rate of SACDL, shorten the coagulation time, and improve the early strength of SACDL. The composite effect of 0.8% calcium formate and 0.5% sodium sulfate is the most significant in promoting coagulation and early strength; the initial setting time and final setting time of the slurry were shortened to 5 min and 10 min, respectively; and the 3 h compressive strength was capable of reaching 16.7 MPa, 31% higher than that of the blank group. In addition, X-ray diffraction and SEM morphology observation were used to study the composition of the hydration products and the evolution of the microstructure, which revealed the early hydration mechanism of SACDL under the synergistic effect of the composite early strength agent: (1) The solubility of tricalcium aluminate (C3A) and dihydrate gypsum (CaSO4·2H2O) increased under the low content composite early strength agent condition, which increased the ettringite (AFt) formation rate. HCOO− was able to penetrate the hydration layers of tricalcium silicate (C3S) and dicalcium silicate (C2S), accelerating the dissolution of C3S and C2S and promoting the early hydration of SACDL. (2) Under the condition of a high dosage of the composite early strength agent, the further increase in Ca2+ concentration promoted the crystallization nodules and precipitation of CH and accelerated the formation of calcium silicate hydrate (C-S-H) gel. C-S-H was filled between a large number of rod-like AFt crystals, thus making the structure more dense.

Non-alcoholic Fatty Liver Disease (NAFLD) is a chronic liver disease that is strongly related to insulin resistance and metabolic syndrome, and it has become the most common liver disorder in developed countries. NAFLD embraces the full pathological process of three conditions: steatosis, non-alcoholic steatohepatitis, and finally, cirrhosis. As NAFLD progresses, symptoms will become increasingly severe as fibrosis develops. Therefore, evaluating the fibrosis stage is crucial for patients with NAFLD. A liver biopsy is currently considered the gold standard for staging fibrosis. However, due to the limitations of liver biopsy, non-invasive alternatives were extensively studied and validated in patients with NAFLD. The advantages of non-invasive methods include their high safety and convenience compared with other invasive approaches. This review introduces the non-invasive methods, summarizes their benefits and limitations, and assesses their diagnostic performance for NAFLD-induced fibrosis.

AimsTo date, the prognostic effects of permanent pacemaker implantation (PPI) after transcatheter aortic valve replacement (TAVR) remain controversial. The purpose of this meta-analysis was to investigate the mid- (1 year) to long-term (> 1 year) clinical and echocardiographic effects of post-procedural PPI in patients after TAVR.MethodsPubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched from the establishment of databases up to 1 December 2021. Studies comparing clinical and echocardiographic outcomes between patients with and without post-TAVR PPI of ≥ 1-year follow-up were collected for further meta-analysis.ResultsA total of 39 studies comprising of 83,082 patients were included in this meta-analysis. At mid-term follow-up (1 year), the pooled results demonstrated a higher risk of all-cause mortality in patients with post-procedural PPI than those without following TAVR (relative risk (RR), 1.17; 95% CI, 1.10–1.24; P < 0.00001). No significant differences were observed in cardiovascular mortality (RR, 0.86; 95% CI, 0.71–1.03; P = 0.10) or heart failure rehospitalization (RR, 0.91; 95% CI, 0.58–1.44; P = 0.69) at 1-year follow-up. At long-term follow-up (> 1 year), post-TAVR PPI had negative effects on all-cause mortality (RR, 1.18; 95% CI, 1.09–1.28; P < 0.0001) and heart failure rehospitalization (RR, 1.42; 95% CI, 1.18–1.71; P = 0.0002). There was no difference in long-term cardiovascular mortality between the two groups (RR, 1.15; 95% CI, 0.97–1.36; P = 0.11). Left ventricular ejection fraction (LVEF) was not significantly different at baseline (mean difference, 1.40; 95% CI, –0.13–2.93; P = 0.07), but was significantly lower in the PPI group at 1-year follow-up (mean difference, –3.57; 95% CI, –4.88 to –2.26; P < 0.00001).ConclusionOur meta-analysis provides evidence that post-TAVR PPI has negative clinical and echocardiographic effects on patients at mid- to long-term follow-up. Further studies are urgently needed to explore the cause of these complications and optimize the treatment and management of patients requiring permanent pacing after TAVR.Systematic Review Registration[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021289935], identifier [CRD42021289935].

BackgroundNeutrophil counts to high-density lipoprotein cholesterol ratio (NHR), a composite marker of inflammation and lipid metabolism, has been considered as a predictor of clinical outcomes in patients with acute ischemic stroke and acute myocardial infarction. However, the predictive value of NHR for all-cause and cardiovascular mortality in the general population remains unclear.MethodsOur study population comprised 34,335 adults in the United States obtained from the National Health and Nutrition Examination Survey (NHANES) (1999–2014) and were grouped in accordance with tertiles of NHR. Kaplan–Meier curves and log-rank test were used to investigate the differences of survival among groups. Multivariate Cox regression, restricted cubic spline analysis, and subgroup analysis were applied to explore the relationship of NHR with all-cause and cardiovascular mortality.ResultsThe mean age of the study cohort was 49.6 ± 18.2 years and 48.4% were men. During a median follow-up of 82 months, 4,310 (12.6%) all-cause deaths and 754 (2.2%) cardiovascular deaths occurred. In a fully-adjusted Cox regression model, participants in the highest tertile had 29% higher hazard of all-cause mortality than those in the lowest tertile [hazard ratio (HR) = 1.29, 95% CI: 1.19–1.41]. For cardiovascular mortality, the continuously increased HR with 95% CIs among participants in the middle and highest tertile were 1.30 (1.06–1.59) and 1.44 (1.17–1.78), respectively. The restricted cubic spline curve indicated that NHR had a non-linear association with all-cause mortality (p for non-linearity < 0.001) and a linear association with cardiovascular mortality (p for non-linearity = 0.553).ConclusionIncreased NHR was a strong and independent predictor of all-cause and cardiovascular mortality in the general population.

Background: Early identification of individuals at a high risk of cardiovascular disease (CVD) is crucial. This study aimed to construct a nomogram for CVD risk prediction in the general population. Methods: This retrospective study analyzed the data between January 2012 and September 2020 at the Physical Examination Center of the Second Affiliated Hospital of Nanjing Medical University (randomized 7:3 to the training and validation cohorts). The outcome was the occurrence of CVD events, which were defined as sudden cardiac death or any death related to myocardial infarction, acute exacerbation of heart failure, or stroke. The least absolute shrinkage and selection operator (LASSO) method and multivariate logistic regression were applied to screen the significant variables related to CVD. Results: Among the 537 patients, 54 had CVD (10.1%). The median cardiac myosin-binding protein-C (cMyBP-C) level in the CVD group was higher than in the no-CVD group (42.25 pg/mL VS 25.00 pg/mL, p = 0.001). After LASSO selection and multivariable analysis, cMyBP-C (Odds ratio [OR] = 1.004, 95% CI [CI, confidence interval]: 1.000–1.008, p = 0.035), age (OR = 1.023, 95% CI: 0.999–1.048, p = 0.062), diastolic blood pressure (OR = 1.025, 95% CI: 0.995–1.058, p = 0.103), cigarettes per day (OR = 1.066, 95% CI: 1.021–1.113, p = 0.003), and family history of CVD (OR = 2.219, 95% CI: 1.003–4.893, p = 0.047) were associated with future CVD events (p < 0.200). The model, including cMyBP-C, age, diastolic blood pressure, cigarettes per day, and family history of CVD, displayed a high predictive ability with an area under the curve (AUC) of 0.816 (95% CI: 0.714–0.918) in the training cohort (specificity and negative predictive value of 0.92 and 0.96) and 0.774 (95% CI: 0.703–0.845) in the validation cohort. Conclusions: A nomogram based on cMyBP-C, age, diastolic blood pressure, cigarettes per day, and family history of CVD was constructed. The model displayed a high predictive ability.

Aims: This study investigates the association between circulating tumor cells (CTCs) and breast cancer metastasis. Methods: A retrospective study was conducted using patients with histologically confirmed breast cancer recruited from the First Affiliated Hospital of Nanjing Medical University during the period of August 2017–October 2020. We used adjusted logistic regression, the random forest algorithm, and sensitivity analysis to study the association between CTC enumeration and tumor metastasis. Further, we performed next-generation sequencing (NGS) on the CTCs obtained from two patients with breast cancer brain metastasis. Results: A total of 41 out of 116 enrolled patients were identified with tumor metastasis. CTC enumeration was significantly higher in patients with liver metastasis than in those without liver metastasis. Patients with CTCs ≥ 5 exhibited a higher risk of tumor metastasis than those with CTCs < 5 in the adjusted model (odds ratios (OR) = 6.25, 95% confidence interval (CI) = 2.63–15.58). The random forest model identified CTC enumeration as a significant metastasis-related variable with the highest mean decrease accuracy and mean decrease Gini score. No significant association was found between CTCs and visceral metastasis with an OR of 1.29 (95% CI = 0.98–2.05, p = 0.232). Upon further investigating organ-specific metastasis, we found that patients with high CTC levels were more likely to develop liver metastasis (OR = 4.87, 95% CI = 1.34–20.17, p = 0.021). The NGS study of CTCs identified a total of 120 indel mutations (e.g., CNGB1, NTSR1, ZG16). The enriched biological processes were mechanoreceptor differentiation and macrophage activation involved in the immune response. The enriched KEGG pathways included focal adhesion, the PI3K-Akt signaling pathway, and microRNAs involved in cancer. Conclusions: Our study revealed that CTCs ≥ 5 are a risk factor for tumor metastasis in breast cancer patients. In addition, we reported that CTCs ≥ 5 might be associated with a higher risk of liver metastasis in patients with metastatic breast cancer. We have provided the mutational profiles of CTCs based on next-generation sequencing.

The book Just Hierarchies: Why Social Hierarchies Matter in China and the Rest of the World by Daniel A. Bell and Pei Wang aims to answer the following question: 'Should morally justifiable social hierarchies structure our social lives on an everyday basis, including our relations with loved ones?' Bell and Wang respond positively. In this article, I mainly focus on the relations between intimates, examining the arguments from the perspective of social egalitarianism and feminism. Bell and Wang argue that hierarchies involving shifting roles are justified, but I shall argue that the defence of hierarchy in intimate relations is not completely convincing. First, the authors mistake hierarchical societies for hierarchical organisations. I will explain why this conflation is detrimental to the defence of hierarchies. Second, the authors neglect to mention some of the significant moral wrongs perpetuated by hierarchical systems. A hierarchy such as a caste system not only fixes inferior and superior positions but also conveys demeaning messages to those who are lower in rank. In addition, we also need to consider the macro-background of specific interpersonal hierarchies to be able to make sense of the wrongs of intimate hierarchies. Third, the practical implications of the defence of intimate hierarchies are ambiguous. I argue that, ultimately, the authors are not able to defend what they set out to defend at the very beginning of the book. [ABSTRACT FROM AUTHOR]