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Background: The incidence and outcomes of early cardiac complications in patients with intracerebral hemorrhage (ICH) are poorly understood. These cardiac complications may be part of the so-called stroke-heart syndrome in patients with ICH. We investigated this issue in an individual patient data pooled analysis from an international repository of clinical trial data., Methods: We used the Virtual International Stroke Trials Archive to investigate the incidence of cardiac complications within 30 days post-ICH or acute ischemic stroke (AIS). These complications included acute coronary syndrome encompassing myocardial injury, heart failure/left ventricular dysfunction, atrial fibrillation/atrial flutter, other arrhythmia/ECG abnormalities, and cardiorespiratory arrest. We used propensity score matching to compare the incidence of patients with stroke-heart syndrome in patients with ICH with those following AIS. Factors associated with 90-day mortality were evaluated using multivariate logistic regression analysis in the ICH cohort., Results: We pooled data from 8698 participants recruited in acute stroke trials (mean age, 68±12 years; 56% male), of whom 914 (11%) were patients with ICH. Among the patients with ICH, 123 (13%) had stroke-heart syndrome in patients with ICH. Following propensity score matching, a total of 1828 patients (914 for each of the cohorts) were analyzed. While the overall incidence of cardiac events tended to be lower in the ICH group compared with the AIS group (the cumulative incidence freedom from the event, 86.3% [95% CI, 84.1-88.6] versus 83.6% [95% CI, 81.2-86.0]; P =0.100), the incidences cardiac events other than atrial fibrillation/atrial flutter were comparable between the 2 matched groups. The incidence of atrial fibrillation/atrial flutter was significantly lower in the ICH group than in the AIS group ( P <0.001). The multivariate-adjusted analysis found that stroke-heart syndrome in patients with ICH was associated with 90-day mortality (adjusted odds ratio, 1.12 [95% CI, 1.06-1.19]; P <0.001)., Conclusions: Cardiac events are common and negatively affect prognosis in patients with ICH, just as seen in AIS., Competing Interests: Dr Dawson received speaker fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Medtronic, and Pfizer and a travel fee from MicroTransponder, Inc. Dr Dawson also received investigator-initiated research funding grant from the Stroke Association United Kingdom. Dr Lip is a consultant and a speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi Sankyo, and Anthos. No fees are received personally. He is a National Institute for Health and Care Research Senior Investigator and a co-principal investigator of the AFFIRMO project on multimorbidity in AF (grant agreement 899871), the TARGET project on digital twins for personalized management of atrial fibrillation and stroke (grant agreement 101136244), and the ARISTOTELES project on artificial intelligence for management of chronic long-term conditions (grant agreement 101080189), which are all funded by the Horizon Europe Research and Innovation Programme of the European Union. The other authors report no conflicts.

The development of sequencing technology has promoted discovery of variants in the human genome. Identifying functions of these variants is important for us to link genotype to phenotype, and to diagnose diseases. However, it usually requires researchers to visit multiple databases. Here, we presented a one-stop webserver for variant function annotation tools (VCAT, https://biomed.nscc-gz.cn/zhaolab/VCAT/ ) that is the first one connecting variant to functions via the epigenome, protein, drug and RNA. VCAT is also the first one to make all annotations visualized in interactive charts or molecular structures. VCAT allows users to upload data in VCF format, and download results via a URL. Moreover, VCAT has annotated a huge number (1,262,041,068) of variants collected from dbSNP, 1000 Genomes projects, gnomAD, ICGC, TCGA, and HPRC Pangenome project. For these variants, users are able to searcher their functions, related diseases and drugs from VCAT. In summary, VCAT provides a one-stop webserver to explore the potential functions of human genomic variants including their relationship with diseases and drugs., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The epidermal growth factor receptor 1 (EGFR) plays a crucial role in the progression of various malignant tumors and is considered a potential target for treating triple-negative breast cancer (TNBC). However, the effectiveness of representative tyrosine kinase inhibitors (TKIs) used in EGFR-targeted therapy is limited in TNBC patients. In our study, we observed that the TNBC cell lines MDA-MB-231 and MDA-MB-468 exhibited resistance to Gefitinib. Treatment with Gefitinib caused an upregulation of Fascin-1 (FSCN1) protein expression and a downregulation of miR-221-3p in these cell lines. However, sensitivity to Gefitinib was significantly improved in both cell lines with either inhibition of FSCN1 expression or overexpression of miR-221-3p. Our luciferase reporter assay confirmed that FSCN1 is a target of miR-221-3p. Moreover, Gefitinib treatment resulted in an upregulation of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in MDA-MB-231 cells. Using Stattic, a small-molecule inhibitor of STAT3, we observed a significant enhancement in the inhibitory effect of Gefitinib on the growth, migration, and invasion of MDA-MB-231 cells. Additionally, Stattic treatment upregulated miR-221-3p expression and downregulated FSCN1 mRNA and protein expression. A strong positive correlation was noted between the expression of STAT3 and FSCN1 in breast cancer tissues. Furthermore, patients with high expression levels of both STAT3 and FSCN1 had a worse prognosis. Our findings suggest that elevated FSCN1 expression is linked to primary resistance to EGFR TKIs in TNBC. Moreover, we propose that STAT3 regulates the expression of miR-221-3p/FSCN1 and therefore modulates resistance to EGFR TKI therapy in TNBC. Combining EGFR TKI therapy with inhibition of FSCN1 or STAT3 may offer a promising new therapeutic option for TNBC., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Adverse cardiac events following ischaemic stroke (stroke-heart syndrome, SHS) pose a clinical challenge. We investigated the association between initial blood pressure at stroke presentation and the risk of SHS., Methods: We utilised data from the Virtual International Stroke Trials Archive (VISTA). We defined SHS as the incidence of cardiac complications within 30 days post-ischaemic stroke. These presentations included acute coronary syndrome encompassing myocardial injury, heart failure/left ventricular dysfunction, atrial fibrillation/flutter, other arrhythmia/electrocardiogram abnormalities, and cardiorespiratory arrest. Using Cox proportional hazards models, we assessed the risk trajectories for developing SHS and its presentations associated with initial blood pressure. We also explored the risk trajectories for 90-day mortality related to initial blood pressure., Results: From 16,095 patients with acute ischaemic stroke, 14,965 (mean age 69 ± 12 years; 55% male) were analysed. Of these, 1774 (11.8%) developed SHS. The risk of SHS and initial blood pressure showed a U-shaped relationship. The lowest blood pressures (⩽130 mmHg systolic and ⩽55 mmHg diastolic) were associated with the highest risks (adjusted hazard ratio [95%confidence interval]: 1.40 [1.21-1.63]; p  < 0.001, 1.71 [1.39-2.10]; p  < 0.001, respectively, compared to referential blood pressure range).Cardiorespiratory arrest posed the greatest risk at higher blood pressure levels (2.34 [1.16-4.73]; p  = 0.017 for systolic blood pressure >190 mmHg), whereas other presentations exhibited the highest risk at lower pressures. The 90-day mortality risk also followed a U-shaped distribution, with greater risks observed at high blood pressure thresholds., Conclusions: There is a U-shaped relationship between initial blood pressure at ischaemic stroke presentation and the risk of subsequent SHS., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: HI, BH, WKE, JD and AHAR report no conflicts of interest.GYHL reports Consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Anthos. No fees are received personally. He is a National Institute for Health and Care Research (NIHR) Senior Investigator and co-PI of the AFFIRMO project on multimorbidity in AF (grant agreement No 899871), TARGET project on digital twins for personalised management of atrial fibrillation and stroke (grant agreement No 101136244) and ARISTOTELES project on artificial intelligence for management of chronic long term conditions (grant agreement No 101080189), which are all funded by the EU’s Horizon Europe Research & Innovation programme.

Background: The patient clinical phenotypes at particularly high risk for early cardiac complications after a recent acute ischaemic stroke (AIS), that is, stroke-heart syndrome (SHS), remain poorly defined. We utilised hierarchical cluster analysis to identify specific phenotypic profiles associated with this risk., Methods: We gathered data on patients with AIS from the Virtual International Stroke Trials Archive, a global repository of clinical trial data. We examined cardiac complications within 30 days post-stroke, including acute coronary syndrome, heart failure, arrhythmias and cardiorespiratory arrest. We employed hierarchical cluster analysis to define distinct phenotypic risk profiles. The incidence/risk of SHS and 90-day mortality were compared across these profiles., Results: We included 12,482 patients (mean age 69 ± 12 years; 55% male), yielding five phenotypes: Profile 1 (' elderly and AF '), Profile 2 (' young and smoker '), Profile 3 (' young '), Profile 4 (' cardiac comorbidities ') and Profile 5 (' hypertension with atherosclerotic comorbidities '). Profiles 4 and 1 exhibited the highest risk for SHS (adjusted HR (95% CI): 2.01 (1.70-2.38) and 1.26 (1.05-1.51), respectively, compared to Profile 3), while Profiles 5 and 2 showed moderate risk and Profile 3 had the lowest risk. Although Profiles 1 and 4 were at the highest risk for most SHS presentations, Profile 5 had the highest risk for cardiorespiratory arrest (adjusted HR (95% CI): 2.99 (1.22-7.34)). The 90-day mortality risk was stratified by phenotype, with the highest risk observed in Profiles 5, and 4., Conclusions: Hierarchical cluster analysis effectively identified phenotypes with the highest risk of SHS and early mortality in patients with AIS., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: HI, BH, WKE, JD and AHAR report no conflicts of interest.GYHL reports Consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Anthos. No fees are received personally. He is a National Institute for Health and Care Research (NIHR) Senior Investigator and co-PI of the AFFIRMO project on multimorbidity in AF (grant agreement No 899871), TARGET project on digital twins for personalised management of atrial fibrillation and stroke (grant agreement No 101136244) and ARISTOTELES project on artificial intelligence for management of chronic long term conditions (grant agreement No 101080189), which are all funded by the EU’s Horizon Europe Research & Innovation programme.

Denticleless E3 ubiquitin protein ligase homolog (DTL), the substrate receptor of the CRL4A complex, plays a central role in genome stability. Even though the oncogenic function of DTL has been investigated in several cancers, its specific role in hepatocellular carcinoma (HCC) still needs further elucidation. Data from a clinical cohort (n = 209), RNA-sequencing, and public database (TCGA and GEO) were analyzed, indicating that DTL is closely related to patient prognosis and could serve as a promising prognostic indicator in HCC. Functionally, DTL promoted the proliferation, metastasis, and sorafenib resistance of HCC in vitro. In the orthotopic tumor transplantation and tail vein injection model, DTL promoted the growth and metastasis of HCC in vivo. Mechanically, we revealed for the first time that DTL was transcriptionally activated by hypoxia-inducible factor 1α (HIF-1α) under hypoxia and functioned as a downstream effector molecule of HIF-1α. DTL promotes the ubiquitination of SAFB-like transcription modulator (SLTM) and subsequently relieves the transcriptional repression of Notch1. These results suggested that DTL may be a potential biomarker and therapeutic target for HCC., (© 2024. The Author(s).)

Aims: Left ventricular assist device (LVAD) implantation, a therapy for end-stage heart failure, is associated with platelet (PLT) activation. This study aims to evaluate the prognostic impact of PLT count in patients with LVAD implantation., Methods and Results: Data from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) registry were investigated, and patients were divided into three groups according to tertiles. The dynamic change of PLT counts and its associations with long-term outcomes were analysed. The primary outcome was long-term mortality. A total of 19 517 patients who received the first continuous-flow LVAD were identified from the INTERMACS registry. The PLT count underwent a dynamic change towards normalization after LVAD implantation. Compared with intermediate, both high (hazard ratio [HR], 1.09, 95% confidence interval [CI]: 1.01 to 1.17, P = 0.033) and low (HR, 1.18, 95% CI: 1.10 to 1.27, P < 0.001) pre-implant PLT counts were associated with an increased risk of 2 year mortality. Compared with intermediate, a high post-implant PLT count was associated with an increased risk of 4 year mortality (HR, 1.38, 95% CI: 1.26 to 1.52, P < 0.001). Besides, both pre- and post-implant PLT counts exhibit a U-shaped association with the risk of mortality., Conclusions: LVAD implantation could improve the PLT count towards normalization. Abnormal pre-/post-implant PLT counts were independently associated with increased risks of long-term mortality., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Traffic speed prediction plays a fundamental role in traffic management and driving route planning. However, timely accurate traffic speed prediction is challenging as it is affected by complex spatial and temporal correlations. Most existing works cannot simultaneously model spatial and temporal correlations in traffic data, resulting in unsatisfactory prediction performance. In this article, we propose a novel hybrid deep learning approach, named HDL4TSP, to predict traffic speed in each region of a city, which consists of an input layer, a spatial layer, a temporal layer, a fusion layer, and an output layer. Specifically, first, the spatial layer employs graph convolutional networks to capture spatial near dependencies and spatial distant dependencies in the spatial dimension. Second, the temporal layer employs convolutional long short-term memory (ConvLSTM) networks to model closeness, daily periodicity, and weekly periodicity in the temporal dimension. Third, the fusion layer designs a fusion component to merge the outputs of ConvLSTM networks. Finally, we conduct extensive experiments and experimental results to show that HDL4TSP outperforms four baselines on two real-world data sets.

Interferon-induced transmembrane proteins (IFITMs) are upregulated by interferons. They are not only highly conserved in evolution but also structurally consistent and have almost identical structural domains and functional domains. They are all transmembrane proteins and have multiple heritable variations in genes. The IFITM protein family is closely related to a variety of biological functions, including antiviral immunity, tumor formation, bone metabolism, cell adhesion, differentiation, and intracellular signal transduction. The progress of the research on its structure and related functions, as represented by IFITM3, is reviewed.

Background: Assessment of residual thromboembolic risk in patients with atrial fibrillation (AF) prescribed oral anticoagulants (OACs) remains unexplored. We performed hierarchical cluster analysis to identify phenotypic profiles of these patients and their risks of residual thromboembolic events., Methods: We utilised data from non-valvular AF patients on OACs, as documented in phases II and III of the GLORIA-AF (Global Registry on Long-Term Oral Anti-thrombotic Treatment in Patients With Atrial Fibrillation) registry. We performed a hierarchical cluster analysis to identify distinct phenotypic profiles. We compared the incidence and risks of thromboembolic events (composite of ischaemic stroke, transient ischaemic attack, or systemic embolism) and related outcomes (major bleeding and all-cause death) across the profiles. We determined the optimal number of profiles through visual inspection of the generated dendrograms., Results: We included 22,410 patients (mean age 70 ± 8 years; 56% male), from which five phenotypes were identified: profile 1 ("uncontrolled hypertension"), profile 2 ("young with a history of coronary artery disease"), profile 3 ("young and obese"), profile 4 ("frailty"), and profile 5 ("non-paroxysmal AF with tachycardia"). Profile 4 was associated with the highest rates of thromboembolic events (1.66/100 person-years [95% confidence interval, 1.46-1.89]), major bleeding (1.92/100 person-years [1.70-2.16]), and death (6.02/100 person-years [5.62-6.43]). Profile 3 was associated with the lowest risk across all measured outcomes (thromboembolic events, 0.64 events/100 person-years [0.48-0.82]; major bleeding, 0.83 events/100 person-years [0.65-1.04]; and death, 1.44 events/100 person-years [1.21-1.71]). Profile 1 had a moderate thromboembolic event rate (1.04/100 person-years [0.91-1.08]), while profiles 2 and 5 showed lower rates., Conclusions: The phenotypic profiles of patients with AF prescribed OACs identified using hierarchical cluster analysis are associated with distinct residual thromboembolic risks and related outcomes. This approach has the potential to enhance patient risk-stratification and holistic approaches to management., (© 2024. The Author(s).)

Competing Interests: Conflict of interest: None declared.

Aims: Atrial fibrillation (AF) and diabetes mellitus (DM) are both associated with adverse clinical events, but the associations have not been fully elucidated, particularly with concomitant insulin use. This study aimed to analyse the associations between adverse events and DM, as well as adverse events and sole insulin use., Materials and Methods: Our analysis included individuals with AF from the prospective Global Registry on Long-Term Oral Anti-Thrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) registry with 3-year follow-up. Outcomes included all-cause death, major bleeding, cardiovascular (CV) death, myocardial infarction (MI), stroke, thromboembolism and major adverse cardiovascular events (MACE)., Results: A total of 15 861 AF individuals were included (age 70.0 ± 10.2 years; 55% male, 20% Asian), of whom, 3666 had DM (age 70.0 ± 9.5 years ; 59% male, 21% Asian). After adjustment, those with DM had higher risks of all-cause death (hazard ratio [HR]: 1.46, 95% confidence interval [CI]: 1.28-1.66), CV death (HR: 1.53 95% CI: 1.27-1.86), major bleeding (HR: 1.23, 95% CI: 1.01-1.48), MI (HR: 1.50, 95% CI: 1.17-1.94) and MACE (HR: 1.42, 95% CI: 1.23-1.63). Compared to individuals with DM receiving oral hypoglycaemic agents, those receiving insulin alone were associated with increased risks of all-cause death (HR: 2.16, 95% CI: 1.61-2.91), CV death (HR: 2.24, 95% CI: 1.45-3.47), major bleeding (HR: 1.89, 95% CI: 1. 21-2.95), MI (HR: 2.24, 95% CI: 1.31-3.82) and MACE (HR: 2.11, 95% CI: 1.54-2.88)., Conclusions: DM was independently associated with higher risks of all-cause death, CV death, MI, major bleeding and MACE in AF individuals. Individuals receiving insulin alone were associated with higher risks of all-cause death, CV death, MI, major bleeding and MACE., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: The relationship between free fatty acids (FFAs) and the risk of mortality remains unclear. There is a scarcity of prospective studies examining the associations between specific FFAs, rather than total concentrations, of their effect on long-term health outcomes., Objective: To evaluate the correlation between different FFAs and all-cause and cardiovascular mortality in a large, diverse, nationally representative sample of adults in the US, and examine how different FFAs may mediate this association., Methods: This cohort study included unsaturated fatty acids (USFA) and saturated fatty acids (SFA) groups in the US National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014 and provided blood samples for FFAs levels. Multiple model calibration was performed using Cox regression analysis for known risk factors to explore the associations between FFAs and all-cause and cardiovascular mortality., Results: In the group of USFA, 3719 people were included, median follow-up, 6.7 years (5.8-7.8 years). In the SFA group, we included 3900 people with a median follow-up, 6.9 years (5.9-8 years). In the USFA group, myristoleic acid (14:1 n-5) (hazard ratio (HR) 1.02 [1.006-1.034]; P = 0.004), palmitoleic acid (16:1 n-7) (HR 1.001 [1.001-1.002]; P < 0.001), cis-vaccenic acid (18:1 n-7) (HR 1.006 [1.003-1.009]; P < 0.001), nervonic acid (24:1 n-9) (HR 1.007 [1.002-1.012]; P = 0.003), eicosatrienoic acid (20:3 n-9) (HR 1.027 [1.009-1.046]; P = 0.003), docosatetraenoic acid (22:4 n-6) (HR 1.024 [1.012-1.036]; P < 0.001), and docosapentaenoic acid (22:5 n-6) (HR 1.019 [1.006-1.032]; P = 0.005) were positively associated with the all-cause mortality, while docosahexaenoic acid (22:6 n-3) had a statistically lower risk of all-cause mortality (HR 0.998 [0.996-0.999]; P = 0.007). Among the SFA group, palmitic acid (16:0) demonstrated a higher risk of all-cause mortality (HR 1.00 [1.00-1.00]; P = 0.022), while tricosanoic acid (23:0) (HR 0.975 [0.959-0.991]; P = 0.002) and lignoceric acid (24:0) (HR 0.992 [0.984-0.999]; P = 0.036) were linked to a lower risk of all-cause mortality. Besides 23:0 and 24:0, the other FFAs mentioned above were linearly associated with the risks of all-cause mortality., Conclusions: In this nationally representative cohort of US adults, some different FFAs exhibited significant associations with risk of all-cause mortality. Achieving optimal concentrations of specific FFAs may lower this risk of all-cause mortality, but this benefit was not observed in regards to cardiovascular mortality., (© 2024. The Author(s).)

Background: There is a growing burden of non-obese people with diabetes mellitus (DM). However, their cardiovascular risk (CV), especially in the presence of cardiovascular-kidney-metabolic (CKM) comorbidities is poorly characterised. The aim of this study was to analyse the risk of major CV adverse events in people with DM according to the presence of obesity and comorbidities (hypertension, chronic kidney disease, and dyslipidaemia)., Methods: We analysed persons who were enrolled in the prospective Silesia Diabetes Heart Project (NCT05626413). Individuals were divided into 6 categories according to the presence of different clinical risk factors (obesity and CKM comorbidities): (i) Group 1: non-obese with 0 CKM comorbidities; (ii) Group 2: non-obese with 1-2 CKM comorbidities; (iii) Group 3: non-obese with 3 CKM comorbidities (non-obese "extremely unhealthy"); (iv) Group 4: obese with 0 CKM comorbidities; (v) Group 5: obese with 1-2 CKM comorbidities; and (vi) Group 6: obese with 3 CKM comorbidities (obese "extremely unhealthy"). The primary outcome was a composite of CV death, myocardial infarction (MI), new onset of heart failure (HF), and ischemic stroke., Results: 2105 people with DM were included [median age 60 (IQR 45-70), 48.8% females]. Both Group 1 and Group 6 were associated with a higher risk of events of the primary composite outcome (aHR 4.50, 95% CI 1.20-16.88; and aHR 3.78, 95% CI 1.06-13.47, respectively). On interaction analysis, in "extremely unhealthy" persons the impact of CKM comorbidities in determining the risk of adverse events was consistent in obese and non-obese ones (P int =0.824), but more pronounced in individuals aged < 65 years compared to older adults (P int = 0.028)., Conclusion: Both non-obese and obese people with DM and 3 associated CKM comorbidities represent an "extremely unhealthy" phenotype which are at the highest risk of CV adverse events. These results highlight the importance of risk stratification of people with DM for risk factor management utilising an interdisciplinary approach., (© 2024. The Author(s).)

Background: China has undergone a significant socioeconomic transformation over the past few decades due to the implementation of family planning policies. These societal changes have resulted in an increased susceptibility among females to developing cardiometabolic diseases (CMD). Unfortunately, studies investigating the correlation between family planning policies in China and the incidence of CMD remain scarce., Methods: Data from 1,226 females, aged 30 years or older with ≥ 1 live birth, undergoing routine physical examinations between January 2018 and December 2021 were collected, and they were grouped by number of live births 1, 2, and ≥ 3. A binary logistic regression model was employed to examine the association between the number of live births with CMD. Furthermore, the subgroup analysis was performed to elucidate the impact of the implementation of family planning policies with CMD., Results: Women with live births ≥ 3 tended to be older, had higher gravidities, a greater proportion of central obesity, general obesity, hypertension, and dyslipidemia (all P < 0.05). Across the three groups (live birth = 1, =2 and ≥ 3), the odds ratio (OR) with 95% CI for obesity were: 1.00, 3.32 (2.36-4.69), and 5.73 (3.79-8.68); for dyslipidemia were: 1.00, 1.75 (1.29-2.39), and 2.02 (1.38-2.94); and for CMD were: 1.00, 1.91 (1.44-2.54), and 2.15 (1.46-3.15), respectively (all P < 0.05). In addition, based on the different periods of the childbearing policy in China, a subgroup analysis (where age was divided into ≤ 45, 45-65, and ≥ 65 years old) found that each additional live birth increased the prevalence risk of obesity and CMD in the younger generations, while hypertension and dyslipidemia in the elder generation., Conclusions: Higher live births are positively associated with the prevalence of CMD among women in Southwest China. Moreover, giving birth after the implementation of the one-child policy tends to have a higher risk of developing CMD., (© 2024. The Author(s).)

Zinc finger E-box binding homeobox 1 (ZEB1) promotes epithelial-mesenchymal transition (EMT) in carcinogenesis, but its role in embryo implantation has not yet been well studied. In the present study we evaluated the hypothesis that ZEB1-induced EMT is essential for embryo implantation in vivo. Endometrial epithelium from female Kunming mice (non-pregnant, and pregnant from day 2.5 to 6.5) were collected for assessment of mRNA/protein expression of ZEB1, and EMT markers E-cadherin and vimentin, by employment of real-time quantitative reverse transcription PCR, Western blot, and immunohistochemical staining. To test if knockdown of ZEB1 affects embryo implantation in vivo, mice received intrauterine injection of shZEB1 before the number of embryos implanted was counted. The results showed that, ZEB1 was highly expressed at both mRNA and protein levels in the mouse endometrium on day 4.5 of pregnancy, paralleled with down-regulated E-cadherin and up-regulated vimentin expression (P < 0.05). Intrauterine injection of shZEB1 markedly suppressed embryo implantation in mice (P < 0.01). Conclusively, the present work demonstrated that ZEB1 is essential for embryo implantation under in vivo condition, and is possibly due to its effect on modulation of endometrial receptivity through EMT., (© 2024. The Author(s).)

Background: Acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) carries a high mortality risk. Inflammation and nutrition are involved in the pathogenesis and prognosis of both AMI and CS. The advanced lung cancer inflammation index ratio (ALI) combines the inflammatory and nutritional status. Our present study aimed to explore the prognostic value of ALI in patients with CS following AMI., Methods: In total, 217 consecutive patients with AMI complicated by CS were divided into two groups based on the ALI admissions cut-off: ≤ 12.69 and > 12.69. The primary endpoint of this study was 30-day all-cause mortality. The secondary endpoints were gastrointestinal hemorrhage and major adverse cardiovascular events (MACEs), including 30-day all-cause mortality, atrioventricular block, ventricular tachycardia/ventricular fibrillation, and nonfatal stroke. The association of ALI with the study endpoints was analyzed by Cox regression analysis., Results: During the 30-day follow-up period after admission, 104 (47.9%) patients died and 150 (69.1%) suffered MACEs. The Kaplan-Meier analysis revealed significantly higher cumulative mortality and lower MACE rates in the low-ALI group compared to the high-ALI group (both log-rank p < 0.001). The 30-day mortality rate was significantly higher in patients with ALI ≤ 12.69 compared to ALI > 12.69 (72.1% vs. 22.6%; p < 0.001). Furthermore, the incidence of MACEs was higher in patients with ALI ≤ 12.69 (85.6% vs. 51.9%; p < 0.001). The receiver operating curve showed that ALI had a modest predictive value (area under the curve [AUC]: 0.789, 95% confidence interval [CI]: 0.729, 0.850). After multivariable adjustment, ALI ≤ 12.69 was an independent predictor for both 30-day all-cause mortality (hazard ratio [HR]: 3.327; 95% CI: 2.053, 5.389; p < 0.001) and 30-day MACEs (HR: 2.250; 95% CI 1.553, 3.260; p < 0.001). Furthermore, the addition of ALI to a base model containing clinical and laboratory data statistically improved the predictive value., Conclusions: Assessing ALI levels upon admission can provide important information for the short-term prognostic assessment of patients with AMI complicated by CS. A lower ALI may serve as an independent predictor of increased 30-day all-cause mortality and MACEs., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 The Author(s). Published by IMR Press.)

Background: Trimethylamine-N-oxide (TMAO) is linked with obesity, while limited evidence on its relationship with body fat distribution. Herein, we investigated the associations between serum TMAO and longitudinal change of fat distribution in this prospective cohort study., Methods: Data of 1964 participants (40-75y old) from Guangzhou Nutrition and Health Study (GNHS) during 2008-2014 was analyzed. Serum TMAO concentration was quantified by HPLC-MS/MS at baseline. The body composition was assessed by dual-energy X-ray absorptiometry at each 3-y follow-up. Fat distribution parameters were fat-to-lean mass ratio (FLR) and trunk-to-leg fat ratio (TLR). Fat distribution changes were derived from the coefficient of linear regression between their parameters and follow-up duration., Results: After an average of 6.2-y follow-up, analysis of covariance (ANCOVA) and linear regression displayed women with higher serum TMAO level had greater increments in trunk FLR (mean ± SD: 1.47 ± 4.39, P -trend  = 0.006) and TLR (mean ± SD: 0.06 ± 0.24, P -trend  = 0.011). Meanwhile, for women in the highest TMAO tertile, linear mixed-effects model (LMEM) analysis demonstrated the annual estimated increments (95% CI) were 0.03 (95% CI: 0.003 - 0.06, P = 0.032) in trunk FLR and 1.28 (95% CI: -0.17 - 2.73, P = 0.083) in TLR, respectively. In men, there were no similar significant observations. Sensitivity analysis yielded consistent results., Conclusion: Serum TMAO displayed a more profound correlation with increment of FLR and TLR in middle-aged and older community-dwelling women in current study. More and further studies are still warranted in the future., Trial Registration: NCT03179657., (© 2024. The Author(s).)

This study aimed to evaluate the safety of Moringa by comparing the effects of different gavage doses of Moringa. The general behavior, body weight, food intake, blood indexes, serum biochemical indexes, and histopathology of rats were used to determine the safety threshold and to provide a reference for the further development and use of Moringa as animal feed. 40 Sprague Dawley rats were selected and given transoral gavage for 28 consecutive days. The T1, T2 and T3 groups were observed for general behavior, body weight, and food intake. Blood and serum biochemical indices were quantified, and histopathology was performed to evaluate the effect and safety of Moringa. The results of the toxicological test showed that (1) Only T1 groups experienced diarrhea. (2) The body weight and food intake of rats in each group were normal compared with the control group. (3) The hematological and serum biochemical indices of rats in the T1 group were significantly different from those of CK but were in the normal range; (4) The results of microscopic examination of the heart, liver, spleen, lung, and kidney of rats in each group were normal, but inflammation occurred in stomach and jejunum of rats in the T1 group, but not in the ileum. The gastrointestinal tract of rats in the T2 and T3 groups were normal. (5) No abnormal death occurred in any of the treatment groups.The results of this study revealed that gavage of Moringa homogenate at a dose of 6 g/kg BW can cause diarrhea in rats. Although there is no pathological effect on weight, food intake, blood and serum biochemical indicators in rats, there are pathological textures in the gastrointestinal tissue caused by diarrhea. Therefore, the safety threshold of Moringa homogenate should be ≤ 3 g/kg BW., (© 2024. The Author(s).)

Although some studies have reported on the expression and clinical significance of Fascin-1 (FSCN1) in liver cancer, the clinical application and differential diagnosis value of FSCN1 in liver cancer are still unclear. The aim of this study was to analyze the expression level of FSCN1 protein in liver cancer tissues and explore its diagnostic and application value in differentiating between hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The immunehistochemical analysis was used to detect the expression of FSCN1 in 108 cases of HCC, 26 cases of ICC, 23 cases of liver cirrhosis, and 11 cases of normal liver tissues. The differences in the positive expression rate and strong positive expression rate of FSCN1 among different groups were analyzed. The positive rate of FSCN1 in normal liver tissues, liver cirrhosis, HCC, and ICC tissues was 0.0% (0/11), 0.0% (0/23), 13.9% (15/108), and 92.3% (24/26), respectively, while the strong positive rate was 0.0% (0/11), 0.0% (0/23), 0.9% (1/108), and 69.2% (18/26), respectively. Both the positive rate and strong positive rate of FSCN1 in ICC tissues were significantly higher than those in HCC, liver cirrhosis, and normal liver tissues. Additionally, the positive rate of FSCN1 in moderately to poorly differentiated HCC tissues was 18.8% (15/80), significantly higher than in well-differentiated HCC (0.0%, 0/28) (P = 0.031). In liver cancer, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FSCN1 positive prediction for ICC were 92.3%, 86.1%, 61.5%, and 97.9%, respectively, whereas the sensitivity, specificity, PPV, and NPV of FSCN1 strong positive prediction for ICC were 69.2%, 99.1%, 94.7%, and 93.0%, respectively. These results suggest that FSCN1 may play an important role in the occurrence and progression of liver cancer, and it can be used as a novel diagnostic marker for ICC., (© 2024. The Author(s).)

Twin and family studies have established the genetic contribution to idiopathic generalized epilepsy (IGE). The genetic architecture of IGE is generally complex and heterogeneous, and the majority of the genetic burden in IGE remains unsolved. We hypothesize that gene-gene interactions contribute to the complex inheritance of IGE. CNTN2 (OMIM* 615,400) variants have been identified in cases with familial adult myoclonic epilepsy and other epilepsies. To explore the gene-gene interaction network in IGE, we took the CNTN2 gene as an example and investigated its co-occurrent genetic variants in IGE cases. We performed whole-exome sequencing in 114 unrelated IGE cases and 296 healthy controls. Variants were qualified with sequencing quality, minor allele frequency, in silico prediction, genetic phenotype, and recurrent case numbers. The STRING&#95;TOP25 gene interaction network analysis was introduced with the bait gene CNTN2 (denoted as A). The gene-gene interaction pair mode was presumed to be A + c, A + d, A + e, with a leading gene A, or A + B + f, A + B + g, A + B + h, with a double-gene A + B, or other combinations. We compared the number of gene interaction pairs between the case and control groups. We identified three pairs in the case group, CNTN2 + PTPN18, CNTN2 + CNTN1 + ANK2 + ANK3 + SNTG2, and CNTN2 + PTPRZ1, while we did not discover any pairs in the control group. The number of gene interaction pairs in the case group was much more than in the control group (p = 0.021). Taking together the genetic bioinformatics, reported epilepsy cases, and statistical evidence in the study, we supposed CNTN2 as a candidate pathogenic gene for IGE. The gene interaction network analysis might help screen candidate genes for IGE or other complex genetic disorders., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Nasopharyngeal carcinoma (NPC) originates in the epithelial cells of the nasopharynx and is a common malignant tumor in southern China and Southeast Asia. Metastasis of NPC remains the main cause of death for NPC patients even though the tumor is sensitive to radiotherapy and chemotherapy. Here, we found that the transmembrane protein tetraspanin1 (TSPAN1) potently inhibited the in vitro migration and invasion, as well as, the in vivo metastasis of NPC cells via interacting with the IKBB protein. In addition, TSPAN1 was essential in preventing the overactivation of the NF-kB pathway in TSPAN1 overexpressing NPC cells. Furthermore, reduced TSPAN1 expression was associated with NPC metastasis and the poor prognosis of NPC patients. These results uncovered the suppressive role of TSPAN1 against NF-kB signaling in NPC cells for preventing NPC metastasis. Its therapeutic value warrants further investigation., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Traffic congestion prediction has become an indispensable component of an intelligent transport system. However, one limitation of the existing methods is that they treat the effects of spatio-temporal correlations on traffic prediction as invariable during modeling spatio-temporal features, which results in inadequate modeling. In this paper, we propose an attention-based spatio-temporal 3D residual neural network, named AST3DRNet, to directly forecast the congestion levels of road networks in a city. AST3DRNet combines a 3D residual network and a self-attention mechanism together to efficiently model the spatial and temporal information of traffic congestion data. Specifically, by stacking 3D residual units and 3D convolution, we proposed a 3D convolution module that can simultaneously capture various spatio-temporal correlations. Furthermore, a novel spatio-temporal attention module is proposed to explicitly model the different contributions of spatio-temporal correlations in both spatial and temporal dimensions through the self-attention mechanism. Extensive experiments are conducted on a real-world traffic congestion dataset in Kunming, and the results demonstrate that AST3DRNet outperforms the baselines in short-term (5/10/15 min) traffic congestion predictions with an average accuracy improvement of 59.05%, 64.69%, and 48.22%, respectively.

Dementia, with homocysteine (Hcy) as an important risk factor, is a severe public health problem in the aging society. Betaine serves as a methyl donor and plays an important role in reducing Hcy. However, the effects and mechanisms of betaine on Hcy-induced cognitive impairment remain unclear. Firstly, SD rats were injected with Hcy (400 μg/kg) through vena caudalis, and betaine (2.5 % w/v) was supplemented via drinking water for 14 days. Betaine supplementation could attenuate Hcy-induced cognitive impairment in the Y maze and novel object recognition tests by repairing brain injury. Meanwhile, microglial activation was observed to be inhibited by betaine supplementation using immunofluorescence and sholl analysis. Secondly, HMC3 cells were treated with betaine, which was found to decrease the ROS level, ameliorate cell membrane rupture, reduce the release of LDH, IL-18 and IL-1β, and attenuate the damage of microglia to neurons. Mechanistically, betaine alleviates cognitive impairment by inhibiting microglial pyroptosis via reducing the expressions of NLRP3, ASC, pro-caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-18 and IL-1β. Betaine treatment can increase SAM/SAH ratio, confirming its enhancement on methylation capacity. Furthermore, betaine treatment was found to enhance N 6 -methyladenosine (m 6 A) modification of NLRP3 mRNA, and reduced the NLRP3 mRNA stability through increasing the expression of the m 6 A reader YTH N 6 -methyladenosine RNA binding protein 2 (YTHDF2). Finally, silencing YTHDF2 could reverse the inhibitory effect of betaine on pyroptosis. Our data demonstrated that betaine attenuated Hcy-induced cognitive impairment by suppressing microglia pyroptosis via inhibiting the NLRP3/caspase-1/GSDMD pathway in an m 6 A-YTHDF2-dependent manner., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Twelve studies involving 433 patients were included. After RDN treatment, LVMI decreased by 13.08 g/m 2 (95% confidence interval [CI]: -18.38, -7.78; p < .00001), PWTd decreased by 0.60 mm (95% CI: -0.87, -0.34; p < .00001), IVSTd decreased by 0.78 mm (95% CI: -1.06, -0.49; p < .00001), and LVEF increased by 1.80% (95% CI: 0.71, 2.90; p = .001). However, there were no statistically significant improvements in LVIDd (95% CI: -1.40, 0.24; p = .17) and diastolic function (E/A) (95% CI: -0.04, 0.14; p = .28). Drug treatment for resistant hypertension (RH) is challenging. Renal denervation (RDN) is one of the most promising treatments for RH. Although studies have shown RDN can control blood pressure, the impacts of RDN on cardiac remodeling and cardiac function are unclear. This meta-analysis evaluated the effect of RDN on cardiac structure and function in patients with RH. PubMed, Embase, and Cochrane were used to conduct a systematic search. The main inclusion criteria were studies on patients with RH who received RDN and reported the changes in echocardiographic parameters before and after RDN. Echocardiographic parameters included left ventricular mass index (LVMI), end-diastolic left ventricular internal dimension (LVIDd), left ventricular end-diastolic posterior wall thickness (PWTd), end-diastolic interventricular septum thickness (IVSTd), E/A, and left ventricular ejection fraction (LVEF). Data was analyzed using RevMan. Twelve studies involving 433 patients were included. After RDN treatment, LVMI decreased by 13.08g/m2 (95%confidence interval [CI]: -18.38, -7.78, p < .00001), PWTd decreased by 0.60mm (95% CI: -0.87, -0.34, p < 0.00001), IVSTd decreased by 0.78mm (95% CI: -1.06, -0.49, p < .00001), and LVEF increased by 1.80% (95% CI: 0.71, 2.90, p = .001). However, there were no statistically significant improvements in LVIDd (95% CI: -1.40, 0.24, p = .17) and diastolic function (E/A) (95% CI: -0.04, 0.14, p =.28). This meta-analysis finds that RDN can improve left ventricular hypertrophy and ejection fraction in patients with RH but has no significant effect on LVIDd and diastolic function. However, more studies are warranted due to the lack of a strict control group, a limited sample size, and research heterogeneity., (© 2024 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

Studies have reported inconsistent results about the risk of incident chronic kidney disease (CKD) in people with metabolically healthy obesity (MHO). We designed this systematic review and meta-analysis to evaluate the risk of developing CKD in people with MHO and metabolically unhealthy normal weight (MUNW). We used a predefined search strategy to retrieve eligible studies from multiple databases up to June 20, 2022. Random-effects model meta-analyses were implied to estimate the overall hazard ratio (HR) of incident CKD in obesity phenotypes. Eight prospective cohort studies, including approximately 5 million participants with a median follow-up ranging between 3 and 14 years, were included in this meta-analysis. Compared to the metabolically healthy normal weight (MHNW), the mean differences in cardiometabolic and renal risk factors in MHO, MUNW, and metabolically unhealthy obesity (MUO) were evaluated with overall HR of 1.42, 1.49, and 1.84, respectively. Compared to MHNW, the mean estimated glomerular filtration rate (eGFR) and high-density lipoprotein (HDL) were significantly lower, and low-density lipoprotein (LDL), blood pressure, blood glucose, and triglycerides were higher in MHO and MUNW. In conclusion, MHO and MUNW are not benign conditions and pose a higher risk for incident CKD. Obesity, whether in the presence or absence of metabolic health, is a risk factor for CKD., (© 2023 World Obesity Federation.)

Background: Ventricular functional mitral regurgitation (FMR) is a common morbidity in patients with heart failure (HF). In addition to guideline-directed medical therapy, mitral valve (MV) repair or replacement has become an option for such patients. However, the impact of different treatments on cardiac remodeling, function, and clinical outcomes remains unclear., Methods: We systematically searched PubMed, EMBASE, Medline, Clinical Trials.gov, and the Cochrane Central Register of Controlled Trials with search terms related to mitral regurgitation, mitral valve repair, surgical mitral valve replacement, mitral annuloplasty device, and MitraClip. The outcomes were left ventricular ejection fraction (LVEF), left ventricular (LV) remodeling, all-cause mortality, cardiovascular death, and HF hospitalization. Sensitivity analysis was performed by removing high-bias risk studies. The analysis was done by Review Manager 5.4 Analyzer and MedCalc Statistical Software version 19.2.6., Results: This meta-analysis included 10 studies with a total of 2533 patients (567 with transcatheter MitraClip, 823 with surgical MV repair, 651 with surgical MV replacement, and 492 with medical therapy). Our meta-analysis revealed that surgical MV repair had significant improvement in LVEF compared to the surgical MV replacement (mean differences (MD) 2.32, [95% CI 0.39, 4.25]), while transcatheter MitraClip treatment was associated with LVEF reduction (MD -4.82, [95% CI -7.29, -2.34]). In terms of LV remodeling, transcatheter MitraClip treatment was associated with improvement in left ventricular end-diastolic volume (MD -10.36, [95% CI -18.74, -1.99]). Furthermore, compared to surgical MV replacement, surgical MV repair was not associated with a reduction of all-cause mortality (risk ratio (RR) 0.83, [95% CI 0.61, 1.13]) and cardiovascular death (RR 0.95, [95% CI 0.56, 1.62]), while transcatheter MitraClip was associated with reduced risk of all-cause mortality (RR 0.87, [95% CI 0.78, 0.98])., Conclusions: Surgical MV repair was associated with significant improvement in LVEF but had no significant effect on all-cause mortality compared to surgical MV replacement. Transcatheter MitraClip was associated with better long-term survival than the non-MitraClip group, thus, transcatheter MitraClip could be considered an alternative treatment in patients with HF-complicated ventricular FMR., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 The Author(s). Published by IMR Press.)

Background: Hepatocellular carcinoma (HCC) continues to increase in morbidity and mortality among all types of cancer. DNA methylation, an important epigenetic modification, is associated with cancer occurrence and progression. The objective of this study was to establish a model based on DNA methylation risk scores for identifying new potential therapeutic targets in HCC and preventing cancer progression., Methods: Transcriptomic, clinical, and DNA methylation data on 374 tumor tissues and 50 adjacent normal tissues were downloaded from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma database. The gene expression profiles of the GSE54236 liver cancer dataset, which contains data on 161 liver tissue samples, were obtained from the Gene Expression Omnibus database. We analyzed the relationship between DNA methylation and gene expression levels after identifying the differentially methylated and expressed genes. Then, we developed and validated a risk score model based on the DNA methylation-driven genes. A tissue array consisting of 30 human hepatocellular carcinoma samples and adjacent normal tissues was used to assess the protein and mRNA expression levels of the marker genes by immunohistochemistry and qRT-PCR, respectively., Results: Three methylation-related differential genes were identified in our study: GLS, MEX3B, and GNA14. The results revealed that their DNA methylation levels were negatively correlated with local gene expression regulation. The gene methylation levels correlated strongly with the prognosis of patients with liver cancer. This was confirmed by qRT-PCR and immunohistochemical verification of the expression of these genes or proteins in tumors and adjacent tissues. These results revealed the relationship between the level of relevant gene methylation and the prognosis of patients with liver cancer as well as the underlying cellular and biological mechanisms. This allows our gene signature to provide more accurate and appropriate predictions for clinical applications., Conclusion: Through bioinformatics analysis and experimental validation, we obtained three DNA methylation marker: GLS, MEX3B, and GNA14. This helps to predict the prognosis and may be a potential therapeutic target for HCC patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Luo, Zhu, Chen, Yang, Huang and Zhang.)

Introduction: Chronic fluid accumulation or congestion is considered an important pathophysiologic mechanism in heart failure, leading to cardinal symptoms such as dyspnea, pulmonary congestion, and pitting edema. Edema index (EI) recently emerged as a surrogate for extracellular volume status and has been proven to be able to reflect one's congestion status. In this study, we aimed to evaluate the prognostic value of EI in patients with chronic heart failure (CHF)., Methods: A total of 401 consecutive patients with CHF between August 2019 and October 2021 were prospectively enrolled. EI was obtained by InBody S10. The primary endpoint was long-term all-cause and cardiovascular mortality., Results: Patients with high EI (>0.397) tended to be older, presented with atrial fibrillation, have higher N-terminal brain natriuretic peptide, and have higher creatinine (all p < 0.05). During a median follow-up of 1200 days, the all-cause and cardiovascular mortality rate was significantly higher in the high EI group compared to the low EI group (all-cause mortality rate 43.8% vs. 30.3%, p < 0.001, and cardiovascular mortality rate 17.5% vs. 13.0%, p < 0.001, respectively). In the multivariate Cox proportional hazard analysis, EI > 0.397 was an independent predictor for both all-cause mortality (HR 1.959; 95% CI 1.304, 2.944; p = 0.001) and cardiovascular mortality (HR 2.051; 95% CI 1.276, 3.296; p = 0.003)., Conclusions: Admission EI could be used as a marker for predicting long-term mortality in patients with CHF, and higher EI was associated with an increased risk of all-cause and cardiovascular mortality. Furthermore, EI-guided management could be a promising therapy in patients with CHF., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Ethnopharmacological Relevance: Lobelia chinensis Lour. (LCL) is a common herb used for clearing heat and detoxifying, and it has antitumor activity. Quercetin is one of its important components, which may play an important role in the treatment of hepatocellular carcinoma (HCC)., Aim of the Study: To study the active ingredients of LCL, their mechanism of action on HCC, and lay the foundations for the development of new drugs for the treatment of HCC., Materials and Methods: Network pharmacology was used to examine the probable active ingredients and mechanisms of action of LCL in HCC treatment. Based on an oral bioavailability of ≥30% and a drug-likeness index of ≥0.18, relevant compounds were selected from the Traditional Chinese Medicine Systems Pharmacology database and TCM Database@Taiwan. HCC-related targets were identified using gene cards and the Online Mendelian Inheritance in Man (OMIM) database. A Venn diagram was created to assess the relationship between the intersection of disease and medication targets by creating a protein-protein interaction network, and the hub targets were selected by topology. Gene Ontology enrichment analyses were performed using the DAVID tool. Finally, in vivo and in vitro experiments (qRT-PCR, western blotting, hematoxylin and eosin staining, transwell assays, scratch tests, and flow cytometry assays) verified that LCL demonstrated notable therapeutic effects on HCC., Results: In total, 16 bioactive LCL compounds met the screening criteria. The 30 most important LCL therapeutic target genes were identified. Of these, AKT1 and MAPK1 were the most important target genes, and the AKT signaling pathway was identified as the key pathway. Transwell and scratch assays showed that LCL prevented cell migration, and flow cytometry tests revealed that the LCL-treated group showed a considerably higher rate of apoptosis than the control group. LCL reduced tumor formation in mice in vivo, and Western blot analysis of tumor tissues treated with LCL indicated variations in PTEN, p-MAPK and p-AKT1 levels. The results show that LCL may inhibit the progression of HCC through the PTEN/AKT signaling pathway to achieve the goal of treating HCC., Conclusion: LCL is a broad-spectrum anticancer agent. These findings reveal potential treatment targets and strategies for preventing the spread of cancer, which could aid in screening potential traditional Chinese medicine for anticancer and clarifying their mechanisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Cardiogenic shock (CS) is the most critical complication after acute myocardial infarction (AMI) with mortality above 50%. Both blood urea nitrogen and left ventricular ejection fraction were important prognostic indicators. We aimed to evaluate the prognostic value of admission blood urea nitrogen to left ventricular ejection fraction ratio (BUNLVEFr) in patients with AMI complicated by CS (AMI-CS)., Methods: 268 consecutive patients with AMI-CS were divided into two groups according to the admission BUNLVEFr cut-off value determined by Youden index. The primary endpoint was 30-day all-cause mortality and the secondary endpoint was the composite events of major adverse cardiovascular events (MACEs). Cox proportional hazard models were performed to analyze the association of BUNLVEFr with the outcome., Results: The optimal cut-off value of BUNLVEFr is 16.63. The 30-day all-cause mortality and MACEs in patients with BUNLVEFr≥16.63 was significantly higher than in patients with BUNLVEFr&lt;16.63 (30-day all-cause mortality: 66.2% vs. 17.1%, p &lt; 0.001; 30-day MACEs: 80.0% vs. 48.0%, p &lt; 0.001). After multivariable adjustment, BUNLVEFr≥16.63 remained an independent predictor for higher risk of 30-day all-cause mortality (HR = 3.553, 95% CI: 2.125-5.941, p &lt; 0.001) and MACEs (HR = 2.026, 95% CI: 1.456-2.820, p &lt; 0.001). Subgroup analyses found that the effect of BUNLVEFr was consistent in different subgroups (all p-interaction&gt;0.05)., Conclusion: The admission BUNLVEFr provided important prognostic information for AMI-CS patients., (© 2024 S. Karger AG, Basel.)

Purpose: To analyze the epidemiology, pattern, and prevent measurement of pediatric maxillofacial trauma in Xinjiang, China., Patients and Methods: Clinical records of patients aged 0 to 18 years with maxillofacial trauma over the 5 years were reviewed. Epidemiological features of data were collected for the cause of injury, age and sex distribution, frequency and type of injury, localization and frequency of soft tissue injuries, facial bone fractures, and presence of associated injuries. Statistical analyses performed included descriptive analysis, χ 2 test, and logistic regression analyses., Results: Among the 450 patients, 333 were male and 117 were female, with a male-to-female ratio of 3.8:1, the mean age was 9.2±5.4 years; 223 cases were soft tissue injuries and 227 cases were maxillofacial fractures. The 16 to 18-year-old group was the highest, with the prevalence of maxillofacial fractures. The most common cause of pediatric maxillofacial trauma was traffic injuries., Conclusion: The incidence of maxillofacial trauma in pediatric patients correlates with a number of factors, including age, sex, and etiology of trauma. The 16 to 18-year-old group is the most prevalent group for maxillofacial trauma in pediatric patients, and traffic accidents are the leading cause of maxillofacial trauma in pediatric patients., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Aim: The purpose of this study was to explore whether clinical ethical climate mediates the relationship between resilience and moral courage in a population of clinical nurses during COVID-19, and if moral distress faced by nurses is a moderating factor., Background: Resilience can help nurses maintain their personal health during COVID-19 when they face great physical and psychological shock and are prone to health problems. Moral courage, as an ethical competency, helps nursing staff in adhering to the principles and values of professional ethics. There is a strong correlation between resilience and moral courage, but the mechanism by which resilience contributes to moral courage is unclear., Method: A cross-sectional study research is designed. Three hundred thirty clinical nurses from six hospitals in Beijing, Sichuan, and Fujian of China were included between August 2021 and March 2022. The survey instruments include the Nurses' Moral Courage Scale (NMCS), Connor-Davidson Resilience Scale (CD-RISC), Moral Distress Scale-Revised (MDS-R), and Hospital Ethical Climate Scale (HECS)., Results: Ethical climate mediates 15% of the relationship between resilience and moral courage. The association between resilience and ethical climate, as well as the indirect relationship between resilience and moral courage, was modified by moral distress., Discussion: This study investigated the mechanisms by which resilience affects moral courage in clinical nurses in the context of COVID-19, suggesting that moral courage can be increased by alleviating moral distress and increasing ethical climate., Implications for Nursing and Health Policy: This study confirms the mediating effect of moral climate on the relationship between resilience and moral courage, as well as the moderating effect of moral distress. Hospital policymakers should value nurses' psychological resilience and moral courage, develop effective policies to prevent and manage stressors, build social support systems, and create a positive ethical climate., (© 2023 International Council of Nurses.)

A single-nucleotide polymorphism (SNP) rs12252-C of interferon-induced transmembrane protein 3 ( IFITM3 ), resulting in a truncated IFITM3 protein lacking 21 N-terminus amino acids, is associated with severe influenza infection in the Chinese population. However, the effect of IFITM3 rs12252-C on influenza vaccination and the underlying mechanism is poorly understood. Here, we constructed a mouse model with a deletion of 21 amino acids at the N-terminus (NΔ21) of IFITM3 and then compared the antibody response between Quadrivalent influenza vaccine (QIV) immunized wild-type (WT) mice and NΔ21 mice. Significantly higher levels of haemagglutination inhibition (HI) titre, neutralizing antibodies (NAb), and immunoglobulin G (IgG) to H1N1, H3N2, B/Victory, and B/Yamagata viruses were observed in NΔ21 mice compared to WT mice. Correspondingly, the numbers of splenic germinal centre (GC) B cells, plasma cells, memory B cells, QIV-specific IgG + antibody-secreting cells (ASC), and T follicular helper cells (T FH ) in NΔ21 mice were higher compared with WT mice. Moreover, the 21-amino-acid deletion caused IFITM3 translocation from the endocytosis compartment to the periphery of cells, which also prevented the degradation of a co-stimulatory molecule of B cell receptor (BCR) CD81 on the cell surface. More importantly, a more interaction was observed between NΔ21 protein and CD81 compared to the interaction between IFITM3 and CD81. Overall, our study revealed a potential mechanism of NΔ21 protein enhancing humoral immune response by relocation to prevent the degradation of CD81, providing insight into SNP affecting influenza vaccination.

Bisphenol A (BPA) is a widespread environmental pollutant linked to detrimental effects on human health and reduced life expectancy following chronic exposure. This prospective cohort study aimed to examine the association between BPA exposure and mortality in American adults and to explore the potential mitigating effects of dietary quality on BPA-related mortality. This study utilized data from 8761 American adults in the 2003-2016 National Health and Nutrition Examination Survey (NHANES). Urinary BPA levels were employed to assess BPA exposure, and dietary quality was evaluated using the Healthy Eating Index-2015 (HEI-2015). All-cause, cardiovascular disease (CVD), and cancer mortality statuses were determined until December 31, 2019, resulting in a cumulative follow-up of 80,564 person-years. The results showed that the highest tertile of urinary BPA levels corresponded to a 36% increase in all-cause mortality and a 62% increase in CVD mortality compared to the lowest tertile. In contrast, the highest tertile of HEI-2015 scores was associated with a 29% reduction in all-cause mortality relative to the lowest tertile. Although no significant interaction was found between HEI-2015 scores and urinary BPA levels concerning mortality, the association between HEI-2015 scores and both all-cause and CVD mortality was statistically significant at low urinary BPA levels. Continuous monitoring of BPA exposure is crucial for evaluating its long-term adverse health effects. Improving dietary quality can lower all-cause mortality and decrease the risk of all-cause and CVD mortality at low BPA exposure levels. However, due to the limited protective effect of dietary quality against BPA exposure, minimizing BPA exposure remains a vital goal., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Distant metastasis is the primary reason for treatment failure in patients with nasopharyngeal carcinoma (NPC). In this study, we investigated the effect of ulinastatin (UTI) on NPC metastasis and its underlying mechanism. Highly-metastatic NPC cell lines S18 and 58F were treated with UTI and the effect on cell proliferation, migration, and invasion were determined by MTS and Transwell assays. S18 cells with luciferase-expressing (S18-1C3) were injected into the left hind footpad of nude mice to establish a model of spontaneous metastasis from the footpad to popliteal lymph node (LN). The luciferase messenger RNA (mRNA) was measured by quantitative polymerase chain reaction (qPCR), and the metastasis inhibition rate was calculated. Key molecular members of the UTI-related uPA, uPAR, and JAT/STAT3 signaling pathways were detected by qPCR and immunoblotting. UTI suppressed the migration and infiltration of S18 and 5-8F cells and suppressed the metastasis of S18 cells in vivo without affecting cell proliferation. uPAR expression decreased from 24 to 48 h after UTI treatment. The antimetastatic effect of UTI is partly due to the suppression of uPA and uPAR. UTI partially suppresses NPC metastasis by downregulating the expression of uPA and uPAR., (© 2023 Wiley Periodicals LLC.)

Rationale: ST-segment elevation on electrocardiogram (ECG) is an alarming sign. Although acute myocardial infarction (AMI) is the most common cause of ST-segment elevation, many non-ischemic conditions may produce pseudo-ST segment elevation. Spiked Helmet (SH) sign is one of the pseudo-ST segment elevations that is associated with critical illness and high risk of death. SH sign was characterized by an upward shift starting before the onset of the QRS complex; however, we found some patients presented with a peculiar characteristic on ECG with an upward convex ST-segment elevation after the QRS wave but without elevation before the QRS wave, therefore called Semi-SH sign. Also, this electrocardiographic feature exists in patients with critical disease and is related to poor prognosis. The purpose of this case series is to describe the electrocardiographic Semi-SH sign and enhance the awareness of such electrocardiographic manifestation for clinicians., Patients Concerns: This case series explores the possibility of severe infection induced electrocardiographic changes resembling spiked-helmet sign., Diagnoses: Sepsis-induced secondary myocardial injury or coronary vasospasm., Interventions: Gastric decompression, antibiotics, diuretics, advanced life support., Outcomes: The outcome of this case series is the association of the electrocardiographic Semi-SH sign with the prognosis. All 3 patients died several days post manifestation of electrocardiographic Semi-SH sign., Lesson: Like SH sign, electrocardiographic Semi-SH sign is a life-threatening or deadly ECG sign, and therefore early recognition and aggressive treatment are important., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Esophageal squamous cell carcinoma (ESCC) is a highly lethal tumor type, but studies on the ESCC tumor microenvironment are limited. We found that cystatin SN (CST1) plays an important role in the ESCC tumor microenvironment. CST1 has been reported to act as an oncogene in multiple human cancers, but its clinical significance and underlying mechanism in ESCC remain elusive., Methods: We performed ESCC gene expression profiling with data from RNA-sequencing and public databases and found CST1 upregulation in ESCC. Then, we assessed CST1 expression in ESCC by RT‒qPCR and Western blot analysis. In addition, immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) were used to estimate the expression of CST1 in ESCC tissue and serum. Moreover, further functional experiments were conducted to verify that the gain and loss of CST1 in ESCC cell lines significantly influenced the proliferation and metastasis of ESCC. Mass spectrometry, coimmunoprecipitation, and gelatin zymography experiments were used to validate the interaction between CST1 and matrix metalloproteinase 2 (MMP2) and the mechanism of CST1 influence on metastasis in ESCC., Results: Here, we found that CST1 expression was significantly elevated in ESCC tissues and serum. Moreover, compared with patients with low CST1 expression, patients with high CST1 expression had a worse prognosis. Overall survival (OS) and disease-free survival (DFS) were significantly unfavorable in the high CST1 expression subgroup. Likewise, the CST1 level was significantly increased in ESCC serum compared with healthy control serum, indicating that CST1 may be a potential serum biomarker for diagnosis, with an area under the curve (AUC) = 0.9702 and p < 0.0001 by receiver operating curve (ROC) analysis. Furthermore, upregulated CST1 can promote the motility and metastatic capacity of ESCC in vitro and in vivo by influencing epithelial mesenchymal transition (EMT) and interacting with MMP2 in the tumor microenvironment (TME)., Conclusions: Collectively, the results of this study indicated that high CST1 expression mediated by SPI1 in ESCC may serve as a potentially prognostic and diagnostic predictor and as an oncogene to promote motility and metastatic capacity of ESCC by influencing EMT and interacting with MMP2 in the TME., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)

Background: Data on anemia and its effects on patients supported with continuous-flow left ventricular assist devices (LVADs) are lacking., Objectives: This study sought to describe the presence of anemia over time and investigate its association with mortality, quality of life, exercise capacity, and adverse events in LVAD patients., Methods: Adults receiving durable LVADs between 2008 and 2017 were identified from the INTERMACS database. The full cohort was stratified according to anemia severity (no anemia, mild, and moderate-severe)., Results: The analysis of 19,509 patients (females: 21.2%, age: 56.9 ± 12.9 years) showed that moderate-severe anemia affected 45.2% of patients at baseline, 33.5% of them at 6 months, and 32.3% in the fourth year after implantation. The presence of normal hemoglobin was 24.4% before surgery, 32.5% at 6 months, and 36.6% at 4 years after implantation. Multivariable linear mixed-effect regression revealed that the average hemoglobin over time was significantly lower (β, -0.233, 95% confidence interval (CI): -0.282 to -0.185), and the reduction of hemoglobin over time was bigger (β, -0.032 95% CI: -0.035 to -0.028) for LVAD nonsurvivors compared with LVAD survivors. Adjusted Cox regression showed that the severity of preimplant anemia was associated with higher mortality (HR, mild: 1.19; 95% CI: 1.05-1.35 and moderate-severe: 1.44; 95% CI: 1.28-1.62), with similar results in competing risk regression. Anemia progression during follow-up was associated with decreased Kansas City Cardiomyopathy Questionnaire scores and shorter 6-minute walk distances., Conclusions: In patients supported with LVADs, anemia is a frequent comorbidity, and deterioration over time is associated with poor prognosis., (Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objective: Pheochromocytoma is a rare catecholamine-producing neuroendocrine tumour originating from the chromaffin cells of the adrenal medulla or extra-adrenal paraganglia. However, there are few bibliometric studies on Pheochromocytoma. Therefore, this study was employed to summarize the global trends and current status in pheochromocytoma by bibliometric analysis., Materials and Methods: The Web of Science (WOS) core collection database was searched for publications relating to pheochromocytoma from 2001 to 2021. Bibliometric analysis was used to examine the data, and Microsoft Excel was utilized to create bar graphs. In addition, VOSviewer was used to carry out co-authorship analysis, co-citation analysis and co-occurrence analysis. CiteSpace was used to analyze the keywords citation bursts., Results: A total of 8,653 publications published in 1,806 journals by 38,590 authors in 6,117 organizations from 100 countries/regions were included in our study. Among them, USA was the leading countries in terms of total publications and sum of time cited, whereas Eunice Kennedy Shriver Natl Inst Child Hlth & Hum was the leading institutions. The main publications for pheochromocytoma-related articles were Journal of clinical endocrinology &metabolism . Pacak karel and Eisenhofer Graeme were the main contributing authors. The studies on pheochromocytoma could be grouped into five clusters: Treatment, Mechanism, Etiology, Radiology and Hormones study. Moreover, the radiology study, etiology study and some specific keywords such germlines mutation, mesenchymal stem-cells, autophagy, neuroinflammation, neurotoxicity, and hemodynamic instability, may become the hot spots of future., Conclusion: Although the number of articles on pheochromocytoma has fluctuated slightly over the past 20 years, there has been an overall upward trend. In general, precision medicine research on pheochromocytoma, especially metastatic pheochromocytoma, in terms of diagnosis, treatment, and etiology will be a hot research topic in the future. This study helps to understand the research perspectives, hot spots and trends of pheochromocytoma and provide new insight and a basis for future pheochromocytoma research quickly., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huang, Liu, Teng, Peng, Liu, Li, Liang, Zhang and Wang.)