Mechanism of ferroptosis in breast cancer and research progress of natural compounds regulating ferroptosis.

Breast cancer is the most prevalent cancer worldwide and its incidence increases with age, posing a significant threat to women's health globally. Due to the clinical heterogeneity of breast cancer, the majority of patients develop drug resistance and metastasis following treatment. Ferroptosis, a form of programmed cell death dependent on iron, is characterized by the accumulation of lipid peroxides, elevated levels of iron ions and lipid peroxidation. The underlying mechanisms and signalling pathways associated with ferroptosis are intricate and interconnected, involving various proteins and enzymes such as the cystine/glutamate antiporter, glutathione peroxidase 4, ferroptosis inhibitor 1 and dihydroorotate dehydrogenase. Consequently, emerging research suggests that ferroptosis may offer a novel target for breast cancer treatment; however, the mechanisms of ferroptosis in breast cancer urgently require resolution. Additionally, certain natural compounds have been reported to induce ferroptosis, thereby interfering with breast cancer. Therefore, this review not only discusses the molecular mechanisms of multiple signalling pathways that mediate ferroptosis in breast cancer (including metastasis, invasion and proliferation) but also elaborates on the mechanisms by which natural compounds induce ferroptosis in breast cancer. Furthermore, this review summarizes potential compound types that may serve as ferroptosis inducers in future tumour cells, providing lead compounds for the development of ferroptosis-inducing agents. Last, this review proposes the potential synergy of combining natural compounds with traditional breast cancer drugs in the treatment of breast cancer, thereby suggesting future directions and offering new insights.

Optimal therapeutic strategies for hepatic metachronous oligometastatic nasopharyngeal carcinoma: Insights from a retrospective study.

Hepatic metachronous oligometastatic nasopharyngeal carcinoma (hmoNPC) exhibits distinct clinical characteristics compared to other types of metastatic NPC. We investigated the optimal therapy for hmoNPC. 160 patients with hmoNPC treated in Sun Yat-sen University Cancer Center between 2010 and 2021 were retrospectively recruited. A total of 56 patients were classified into the local therapy (LT) cohort, 23 into the systemic therapy (ST) cohort and 81 into the combination therapy (LT + ST) cohort. The median PFS was 7.9 months (95% confidence interval [CI]: 4.1-11.9 months) in the LT cohort, 15.5 months (95% CI: 10.5-32.3 months) in the ST cohort, and 31.3 months (95% CI: 20.3 to NA months) in the LT + ST cohort. The median OS was 41.1 months (95% CI: 30.0-54.0 months) in the LT cohort, 50.4 months (95% CI: 41.5 to NA months) in the ST cohort and not reached (NR) (95% CI: 77.3 to NA months) in the LT + ST cohort. Cox analysis was used to construct nomograms to predict patient outcomes. Among patients with no evidence of disease status after LT, the prognosis was significantly better in the LT + ST cohort than LT cohort (median PFS: NR [95% CI: 29.0 to NA months] vs. 20.0 months [95% CI: 10.4 to NA months]). More survival benefits were achieved with platinum-based chemotherapy than oral monotherapy (median PFS: NR [95% CI: 21.7 to NA months] vs. 17.2 months [95% CI: 10.2 to NA months]). Fewer postoperative early progression events were observed in neoadjuvant chemotherapy cohort than in adjuvant chemotherapy cohort (2.78% vs. 18.81%, P = .013). In conclusion, combining neoadjuvant platinum-based chemotherapy and local therapy was the best strategy for patients with hmoNPC.

Characterization of the m6A/m1A/m5C/m7G-related regulators on the prognosis and immune microenvironment of glioma by integrated analysis of scRNA-seq and bulk RNA-seq data.

BACKGROUND: Proliferation, metabolism, tumor occurrence and development in gliomas are greatly influenced by RNA modifications. However, no research has integrated the four RNA methylation regulators of m6A, m1A, m5C and m7G in gliomas to analyze their relationship with glioma prognosis and intratumoral heterogeneity. METHODS: Based on three in-house single-cell RNA-sequencing (scRNA-seq) data, the glioma heterogeneity and characteristics of m6A/m1A/m5C/m7G-related regulators were elucidated. Based on publicly available bulk RNA-sequencing (RNA-seq) data, a risk-score system for predicting the overall survival (OS) for gliomas was established by three machine learning methods and multivariate Cox regression analysis, and validated in an independent cohort. RESULTS: Seven cell types were identified in gliomas by three scRNA-seq data, and 22 m6A/m1A/m5C/m7G-related regulators among the marker genes of different cell subtypes were discovered. Three m6A/m1A/m5C/m7G-related regulators were selected to construct prognostic risk-score model, including EIFA, NSUN6 and TET1. The high-risk patients showed higher immune checkpoint expression, higher tumor microenvironment scores, as well as higher tumor mutation burden and poorer prognosis compared with low-risk patients. Additionally, the area under the curve values of the risk score and nomogram were 0.833 and 0.922 for 3 year survival and 0.759 and 0.885 for 5 year survival for gliomas. EIF3A was significantly highly expressed in glioma tissues in our in-house RNA-sequencing data (p < 0.05). CONCLUSION: These findings may contribute to further understanding of the role of m6A/m1A/m5C/m7G-related regulators in gliomas, and provide novel and reliable biomarkers for gliomas prognosis and treatment.

ZNF131 facilitates the growth of hepatocellular carcinoma by acting as a transcriptional activator of SMC4 expression.

ZNF131 is a Zinc finger protein that acts as a transcription factor with oncogenic effects in multiple cancers. In this study, we aimed to explore the alternative splicing profile of ZNF131 in hepatocellular carcinoma (HCC), its regulatory effects on cell-cycle progression, and the downstream effectors. ZNF131 transcriptional profile and HCC survival analysis were conducted using data from the Cancer Genome Atlas (TCGA)-Liver Hepatocellular Cancer (LIHC) dataset. Chromatin immunoprecipitation (ChIP)-qPCR and dual-luciferase reporter assays were utilized to explore transcriptional regulation. CCK-8, colony formation and xenograft tumor models were used to study HCC tumor growth. Results showed that ZNF131 isoform 2 is upregulated in HCC tissues and its upregulation was associated with unfavorable overall survival (OS) and progression-free interval (PFI). Knockdown of endogenous ZNF131 inhibits HCC cell growth and induces G2/M cell-cycle arrest. ZNF131 binds to the SMC4 promoter by interacting with ZBTB33 and the ZBTB33 recognizing motif. ZNF131 transcriptionally activates SMC4 expression in HCC cells. The tumor-suppressive effects of ZNF131 shRNA could be partially reversed by enforced SMC4 overexpression. In summary, this study highlights the ZNF131/ZBTB33/SMC4 axis as a driver of pathological cell cycling and proliferation in HCC.

Quercetin inhibits endothelial & hepatocellular carcinoma cell crosstalk via reducing extracellular vesicle-mediated VEGFR2 mRNA transfer.

This study aims to investigate the regulatory effects of quercetin extracellular vesicles (EVs)-mediated expression of vascular endothelial growth factor receptor 2 (VEGFR2) in hepatocellular carcinoma (HCC)-derived circulating tumor cells (CTCs) and the underlying mechanisms. CTCs were isolated from patients with pathologically diagnosed HCC, with VEGFR2 expression visualized by fluorescence in situ hybridization (FISH). The human HCC cell line Huh-7 and SK-HEP-1 were used for in vitro studies to assess EVs uptake, VEGFR2 mRNA transfer, invasion, migration, cancer stem cell (CSC) properties, and VEGF secretion. Results showed that VEGFR2 mRNA was commonly expressed in HCC-CTCs, with a higher incidence in biphenotypic CTCs. Its expression was limited in HCC cell lines, but present in certain liver cells. In vitro experiments confirmed that VEGFR2 mRNA could be transferred to HCC cells via EVs from primary tumor endothelial cells (PTECs), which was impaired by quercetin treatment. Quercetin significantly reduced VEGFR2 mRNA and protein expression in HCC cells, weakened their invasive and metastatic capacities, and diminished VEGFR2-mediated CSC properties. In vivo, quercetin reduced VEGF secretion, impaired angiogenesis, slowed tumor growth, and decreased the number and proportion of VEGFR2-positive CTCs. In summary, VEGFR2 mRNA is present in HCC-CTCs, potentially sourced from PTECs-derived EVs. Quercetin effectively inhibits VEGFR2 expression, impacting HCC cell invasion, metastasis, and CSC characteristics. Besides, it reduces VEGFR2-positive CTCs in vivo. These effects support its therapeutic potential in HCC treatment by targeting the angiogenesis and tumor dissemination pathway.

Non-native plants tend to be phylogenetically distant but functionally similar to native plants under intense disturbance at the Three Gorges Reservoir Area.

Darwin's two opposing hypotheses, proposing that non-native species closely or distantly related to native species are more likely to succeed, are known as 'Darwin's Naturalization Conundrum'. Recently, invasion ecologists have sought to unravel these hypotheses. Studies that incorporate rich observational data in disturbed ecosystems that integrate phylogenetic and functional perspectives have potential to shed light on the conundrum. Using 313 invaded plant communities including 46 invasive plant species and 531 native plant species across the Three Gorges Reservoir Area in China, we aim to evaluate the coexistence mechanisms of invasive and native plants by integrating phylogenetic and functional dimensions at spatial and temporal scales. Our findings revealed that invasive plants tended to co-occur more frequently with native plant species that were phylogenetically distant but functionally similar in the reservoir riparian zone. Furthermore, our study demonstrated that the filtering of flood-dry-flood cycles played a significant role in deepening functional similarities of native communities and invasive-native species over time. Our study highlights the contrasting effects of phylogenetic relatedness and functional similarity between invasive and native species in highly flood-disturbed habitats, providing new sights into Darwin's Naturalization Conundrum.

Abbreviated MRI Protocols in the Abdomen and Pelvis.

Abbreviated MRI (AMRI) protocols rely on the acquisition of a limited number of sequences tailored to a specific question. The main objective of AMRI protocols is to reduce exam duration and costs, while maintaining an acceptable diagnostic performance. AMRI is of increasing interest in the radiology community; however, challenges limiting clinical adoption remain. In this review, we will address main abdominal and pelvic applications of AMRI in the liver, pancreas, kidney, and prostate, including diagnostic performance, pitfalls, limitations, and cost effectiveness will also be discussed. Level of Evidence: 3 Technical Efficacy Stage: 3.

Disentangling the role of environmental filtering and biotic resistance on alien invasions in a reservoir area.

Large-scale water conservancy projects benefit human life but have modified the landscape and provided opportunities for alien plant invasions. Understanding the environmental (e.g., climate), human-related (e.g., population density, proximity to human activities), and biotic (e.g., native plant, community structure) factors driving invasions is essential in the management of alien plants and biodiversity conservation in areas with intense human pressure. To this end, we investigated the spatial patterns of alien plant species distribution in the Three Gorges Reservoir Area (TGRA) of China and distinguished the role of the external environment and community characteristics in determining the occurrence of alien plants with differing levels of known invasion impacts in China using random forest analyses and structural equation models. A total of 102 alien plant species belonging to 30 families and 67 genera were recorded, the majority being annual and biennial herbs (65.7%). The results showed a negative diversity-invasibility relationship and supported the biotic resistance hypothesis. Moreover, percentage coverage of native plants was found to interact with native species richness and had a predominant role in resisting alien plant species. We found alien dominance was mainly the result of disturbance (e.g., changes in hydrological regime), which drove native plant loss. Our results also demonstrated that disturbance and temperature were more important for the occurrence of malignant invaders than all alien plants. Overall, our study highlights the importance of restoring diverse and productive native communities in resistance to invasion.

Do atrophic gastritis and intestinal metaplasia reverse after Helicobacter pylori eradication?

BACKGROUND: It's still controversial whether Helicobacter pylori (H. pylori) eradication can reverse atrophic gastritis (AG) and intestinal metaplasia (IM). Therefore, we performed a meta-analysis to estimate the effect of H. pylori eradication on AG and IM. METHODS: We searched the PubMed, Web of Science and EMBASE datasets through April 2023 for epidemiological studies, which provided mean glandular atrophy (GA) or IM score before and after H. pylori eradication, or provided ORs, RRs or HRs and 95% CIs for the association of AG or IM with H. pylori eradication. Weighted mean difference (WMD) and pooled ORs and 95%CIs were used to estimate the effect of H. pylori eradication on AG and IM. RESULTS: Twenty articles with a total of 5242 participants were included in this meta-analysis. H. pylori eradication significantly decreased GA score in the antrum (WMD -0.36; 95% CI: -0.52, -0.19, p < 0.01), GA score in the corpus (WMD -0.35; 95% CI: -0.52, -0.19, p < 0.01), IM score in the antrum (WMD -0.16; 95% CI: -0.26, -0.07, p < 0.01) and IM score in the corpus (WMD -0.20; 95% CI: -0.37, -0.04, p = 0.01). H. pylori eradication significantly improved AG (pooled OR 2.96; 95% CI: 1.70, 5.14, p < 0.01) and IM (pooled OR 2.41; 95% CI: 1.24, 4.70, p < 0.01). The association remained significant in the subgroup analyses by study design, sites of lesions, regions and follow-up time. Although Publication bias was observed for AG, the association remained significant after trim-and-fill adjustment. CONCLUSIONS: H. pylori eradication could significantly improve AG and IM at early stage.

Single-Cell Transcriptomics Reveals Crucial Cell Subsets and Functional Heterogeneity Associated With Carotid Atherosclerosis and Cerebrovascular Events.

BACKGROUND: Carotid atherosclerosis is a chronic inflammatory disorder and is responsible for the vast majority of ischemic strokes. Inappropriate innate and adaptive immune responses synergize with malfunctional vascular wall cells to cause atherosclerotic lesions. Yet, functional characteristics of specific immune and endothelial cell subsets associated with atherosclerosis and cerebrovascular events are poorly understood. METHODS: Here, using single-cell RNA sequencing, the unprecedentedly largest data set from 20 patients' carotid artery plaques and paired peripheral blood mononuclear cells was generated, with which an ultra-high-precision cellular landscape of the atherosclerotic microenvironment involving 372 070 cells was depicted. RESULTS: Compared with peripheral blood mononuclear cells, 3 plaque-specific T-cell subsets exhibiting proatherogenic features of both activation and exhaustion were identified. Strikingly, usually antiatherogenic, CD4+FOXP3+ regulatory T cells from plaques of patients with symptomatic disease acquired proinflammatory properties by probably converting to T helper 17 and T helper 9 cells, while CD4+NR4A1+/C0 and CD8+SLC4A10+ T cells related to cerebrovascular events possessed atherogenic attributes including proinflammation, polarization, and exhaustion. In addition, monocyte-macrophage dynamics dominated innate immune response. Two plaque-specific monocyte subsets performed diametrically opposed functions, EREG+ monocytes promoted cerebrovascular events while C3+ monocytes are anti-inflammatory. Similarly, IGF1+ and HS3ST2+ macrophages with classical proinflammatory M1 macrophage features were annotated and contributed to cerebrovascular events. Moreover, SULF1+ (sulfatase-1) endothelial cells were also found to participate in cerebrovascular events through affecting plaque vulnerability. CONCLUSIONS: This compendium of single-cell transcriptome data provides valuable insights into the cellular heterogeneity of the atherosclerotic microenvironment and the development of more precise cardiovascular immunotherapies.

Inverse association between maternal serum concentrations of trace elements and risk of spontaneous preterm birth: a nested case-control study in China.

Few studies have evaluated the joint effect of trace elements on spontaneous preterm birth (SPTB). This study aimed to examine the relationships between the individual or mixed maternal serum concentrations of Fe, Cu, Zn, Se, Sr and Mo during pregnancy, and risk of SPTB. Inductively coupled plasma MS was employed to determine maternal serum concentrations of the six trace elements in 192 cases with SPTB and 282 controls with full-term delivery. Multivariate logistic regression, weighted quantile sum regression (WQSR) and Bayesian kernel machine regression (BKMR) were used to evaluate the individual and joint effects of trace elements on SPTB. The median concentrations of Sr and Mo were significantly higher in controls than in SPTB group (P < 0·05). In multivariate logistic regression analysis, compared with the lowest quartile levels of individual trace elements, the third- and fourth-quartile Sr or Mo concentrations were significantly associated with reduced risk of SPTB with adjusted OR (aOR) of 0·432 (95 CI < 0·05). In multivariate logistic regression analysis, compared with the lowest quartile levels of individual trace elements, the third- and fourth-quartile Sr or Mo concentrations were significantly associated with reduced risk of SPTB with adjusted aOR of 0·432 (95 % CI 0·247, 0·756), 0·386 (95 % CI 0·213, 0·701), 0·512 (95 % CI 0·297, 0·883) and 0·559 (95 % CI 0·321, 0·972), respectively. WQSR revealed the inverse combined effect of the trace elements mixture on SPTB (aOR = 0·368, 95 % CI 0·228, 0·593). BKMR analysis confirmed the overall mixture of the trace elements was inversely associated with the risk of SPTB, and the independent effect of Sr and Mo was significant. Our findings suggest that the risk of SPTB decreased with concentrations of the six trace elements, with Sr and Mo being the major contributors.

The Buerger's rabbit model: a closer step to unravelling thromboangiitis obliterans?

OBJECTIVE: Thromboangiitis obliterans (TAO) remains clinical challenging due to its rarity and underwhelming management outcomes. This study aimed to describe a novel TAO rabbit model that demonstrates a closer resemblance to TAO. METHODS: Thirty-six New Zealand rabbits underwent the surgical implantation of calibrated gelatin sponge particles (CGSPs) into their right femoral artery. The CGSPs were soaked in different solutions to simulate different types of thrombi: normal (NT; normal saline); inflammatory TAO thrombus (TAO; dimethylsulfoxide [DMSO]), and DMSO with methotrexate (MTX). All groups underwent clinical assessment, digital subtraction angiography (DSA) and histopathological analysis at time points day 0 (immediate), week 1 (acute), week 2 (subacute), and week 4 (chronic). RESULTS: The TAO rabbit presented with signs of ischemia of the right digit at week 4. On DSA, the TAO rabbits exhibited formation of corkscrew collaterals starting week 1. On H&E staining, gradual CGSP degradation was observed along with increased red blood cell aggregation and inflammatory cells migration in week 1. On week 2, disorganization of the tunica media layer and vascular smooth muscle cell (VSMC) proliferation was observed. In the TAO rabbit, migrated VSMCs, inflammatory cells, and extracellular matrix with collagen-like substances gradually occluded the lumen. On week 4, the arterial lumen of the TAO rabbit was filled with relatively-organized VSMC and endothelial cell clusters with less inflammatory cells. Neorevascularization was found in the MTX-treated group. CONCLUSION: The novel TAO rabbit model shows a closer resemblance to human TAO clinically, radiographically, and histopathologically. Histological analysis of the IT progression in the TAO model suggests that it is of VSMC origin.

Nine new nor-3,4-seco-dammarane triterpenoids from the leaves of Cyclocarya paliurus and their hypoglycemic activity.

This manuscript describes the isolation of nine new nor-3,4-seco-dammarane triterpenoids, norqingqianliusus A-I (1-9) and one known nortriterpenoid (10) from Cyclocarya paliurus leaves. Norqingqianliusus A and B (1 and 2) possess a unique 3,4-seco-dammarane-type C26 tetranortriterpenoid skeleton. The compounds were structurally characterized through modern spectroscopic techniques. Moreover, the potential mechanism of hypoglycemic activity was further explored by studying the effects on glucosamine-induced insulin resistant HepG2 cells. In vitro hypoglycemic effects of all of the isolates were investigated using insulin resistant HepG2 cells. The glucose consumption was significantly promoted by compound 10, in a dose-dependent manner, thus alleviating damage in IR-HepG2 cells. Besides, it reduced the PEPCK and GSK3ß gene expression, involved in glucose metabolism. The anti-diabetic effects of the plant, utilized traditionally, can hence be attributed to the presence of nor-3,4-seco-dammarane triterpenoids in the leaves.

Natural autophagy modulators in non-communicable diseases: from autophagy mechanisms to therapeutic potential.

Non-communicable diseases (NCDs) are defined as a kind of diseases closely related to bad behaviors and lifestyles, e.g., cardiovascular diseases, cancer, and diabetes. Driven by population growth and aging, NCDs have become the biggest disease burden in the world, and it is urgent to prevent and control these chronic diseases. Autophagy is an evolutionarily conserved process that degrade cellular senescent or malfunctioning organelles in lysosomes. Mounting evidence has demonstrated a major role of autophagy in the pathogenesis of cardiovascular diseases, cancer, and other major human diseases, suggesting that autophagy could be a candidate therapeutic target for NCDs. Natural products/phytochemicals are important resources for drugs against a wide variety of diseases. Recently, compounds from natural plants, such as resveratrol, curcumin, and ursolic acid, have been recognized as promising autophagy modulators. In this review, we address recent advances and the current status of the development of natural autophagy modulators in NCDs and provide an update of the latest in vitro and in vivo experiments that pave the way to clinical studies. Specifically, we focus on the relationship between natural autophagy modulators and NCDs, with an intent to identify natural autophagy modulators with therapeutic potential.

Study on agricultural water resource utilization efficiency under the constraint of carbon emission and water pollution.

Agricultural water resource utilization efficiency in China is facing significant challenges due to the dual constraints of carbon emissions and water pollution. The inefficiency in water usage in agriculture not only impacts the sustainability of water resources but also contributes to environmental degradation through increased carbon emissions and water pollution. Agricultural water resource utilization efficiency under the constraint of carbon emission and water pollution has been a critical issue in China from 2005 to 2022. This study employs the Quantile Autoregressive Distributed Lag (QARDL) method to comprehensively assess and analyze the complex relationship that exists between agricultural water usage, carbon emissions, and water pollution. By analyzing distinct quantiles of the data distribution, the research investigates how different levels of water resource utilization efficiency relate to carbon emissions and water pollution under various conditions. The findings reveal nuanced insights into the dynamic interactions among these components within the agricultural sector. This research project focuses on the efficiency of water resource utilization in agriculture while considering the constraints of carbon emission and water pollution. Given the dynamic and time-dependent character of these components, the QARDL methodology makes it possible to get a detailed knowledge of how they interact within the framework of agriculture. The study aims to give significant insights and policy suggestions to improve agricultural practices while minimizing environmental concerns linked to carbon emissions and water pollution.

Biomarkers for congenital ventricular outflow tract malformations based on maternal serum lipid metabolomics analysis.

BACKGROUND: The congenital ventricular outflow tract malformations (CVOTMs) is a major congenital heart diseases (CHDs) subtype, and its pathogenesis is complex and unclear. Lipid metabolic plays a crucial role in embryonic cardiovascular development. However, due to the limited types of detectable metabolites in previous studies, findings on lipid metabolic and CHDs are still inconsistent, and the possible mechanism of CHDs remains unclear. METHODS: The nest case-control study obtained subjects from the multicenter China Teratology Birth Cohort (CTBC), and maternal serum from the pregnant women enrolled during the first trimester was utilized. The subjects were divided into a discovery set and a validation set. The metabolomics of CVOTMs and normal fetuses were analyzed by targeted lipid metabolomics. Differential comparison, random forest and lasso regression were used to screen metabolic biomarkers. RESULTS: The lipid metabolites were distributed differentially between the cases and controls. Setting the selection criteria of P value < 0.05, and fold change (FC) > 1.2 or < 0.833, we screened 70 differential metabolites. Within the prediction model by random forest and lasso regression, DG (14:0_18:0), DG (20:0_18:0), Cer (d18:2/20:0), Cer (d18:1/20:0) and LPC (0:0/18:1) showed good prediction effects in discovery and validation sets. Differential metabolites were mainly concentrated in glycerolipid and glycerophospholipids metabolism, insulin resistance and lipid & atherosclerosis pathways, which may be related to the occurrence and development of CVOTMs. CONCLUSION: Findings in this study provide a new metabolite data source for the research on CHDs. The differential metabolites and involved metabolic pathways may suggest new ideas for further mechanistic exploration of CHDs, and the selected biomarkers may provide some new clues for detection of COVTMs.

Association of maternal phthalates exposure and metabolic gene polymorphisms with congenital heart diseases: a multicenter case-control study.

BACKGROUND: The majority of congenital heart diseases (CHDs) are thought to result from the interactions of genetics and the environment factors. This study aimed to assess the association of maternal non-occupational phthalates exposure, metabolic gene polymorphisms and their interactions with risk of CHDs in offspring. METHODS: A multicenter case-control study of 245 mothers with CHDs infants and 268 control mothers of health infant was conducted from six hospitals. Maternal urinary concentrations of eight phthalate metabolites were measured by ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Twenty single nucleotide polymorphisms (SNPs) in cytochrome P450 family 2 subfamily C member 9 (CYP2C9) and 19 (CYP2C19), uridine diphosphate (UDP) glucuronosyl transferase family 1 member A7 (UGT1A7), family 2 member B7 (UGT2B7) and B15(UGT2B15) genes were genotyped. The multivariate logistic regressions were used to estimate the association between maternal phthalates exposure or gene polymorphisms and risk of CHDs. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene-gene and gene-phthalates exposure interactions. RESULTS: There was no significant difference in phthalate metabolites concentrations between the cases and controls. No significant positive associations were observed between maternal exposure to phthalates and CHDs. The SNPs of UGT1A7 gene at rs4124874 (under three models, log-additive: aOR = 1.74, 95% CI:1.28-2.37; dominant: aOR = 1.86, 95% CI:1.25-2.78; recessive: aOR = 2.50, 95% CI: 1.26-4.94) and rs887829 (under the recessive model: aOR = 13.66, 95% CI: 1.54-121) were significantly associated with an increased risk of CHDs. Furthermore, the associations between rs4124874 (under log-additive and dominant models) of UGT1A7 were statistically significant after the false discovery rate correction. No significant gene-gene or gene-phthalate metabolites interactions were observed. CONCLUSIONS: The polymorphisms of maternal UGT1A7 gene at rs4124874 and rs887829 were significantly associated with an increased risk of CHDs. More large-scale studies or prospective study designs are needed to confirm or refute our findings in the future.

Retrospective analysis of a novel grading system for evaluating the long-term benefit of revascularization on carotid artery stenosis.

OBJECTIVE: To estimate revascularization benefit for carotid artery stenosis, with a novel grading system containing symptoms, stenosis, plaque, and collaterals collateral compensation (SSPC grading system). METHODS: A retrospective multicenter study examined 945 consecutive patients diagnosed with carotid stenosis from January 2013 to December 2017. The cohort was classified into two groups: the revascularization group and the best medical therapy (BMT) group. Demographic, clinical, and lesion characteristics of all patients were recorded and five-year non-procedural stroke survival was calculated using Kaplan-Meier curve analyses. RESULTS: Of the 945 patients, 514 underwent carotid revascularization (483 for carotid endarterectomy [CEA] and 31 for transfemoral-carotid artery stenting [TF-CAS]) and 431 patients were treated with BMT. Patients in the revascularization group had a significantly higher proportion of preprocedural stroke/transient ischemic attack (TIA) and grades of stenosis. Of the patients in the revascularization group, 3.1% were classified as SSPC I, 10.3% as SSPC II, 41.4% as SSPC III, and 45.1% as SSPC IV. Meanwhile, 17.9% were classified as SSPC I, 19.7% as SSPC II, 49.2% as class III, and 13.2% had class IV in the BMT group. Procedural stroke developed in 13 patients (2.5%) following revascularization (10 of them were non-disabling). The overall rate of freedom from any non-procedural stroke was 94.1±1.1% in the revascularization group and 89.5±1.6% in the BMT group (P=0.01). Subgroup analysis was conducted for asymptomatic carotid stenosis (ACS) and carotid near-occlusion (CNO) patients. Non-significance was noted in the rate of freedom from any non-procedural stroke between revascularization and BMT in both ACS and CNO subgroups (P=0.09 and 0.12, respectively). Of note, in ACS patients graded as SSPC III, a significant difference in stroke survival was found between the revascularization and BMT group (96.0±2.0% vs. 89.1±2.4%, P=0.04). Meanwhile, in symptomatic CNO patients, similar results were found regarding SSPC classification (94.8±3.6% vs. 63.8±14.9%, P=0.01). CONCLUSIONS: The SSPC grading system stratifies the patients with carotid artery stenosis and predicts the long-term benefits of revascularization. Meanwhile, potential revascularization benefits could be better attained via SSPC classes in specific patients with ACS and CNO.

Accuracy of deep learning in the differential diagnosis of coronary artery stenosis: a systematic review and meta-analysis.

BACKGROUND: In recent years, as deep learning has received widespread attention in the field of heart disease, some studies have explored the potential of deep learning based on coronary angiography (CAG) or coronary CT angiography (CCTA) images in detecting the extent of coronary artery stenosis. However, there is still a lack of a systematic understanding of its diagnostic accuracy, impeding the advancement of intelligent diagnosis of coronary artery stenosis. Therefore, we conducted this study to review the accuracy of image-based deep learning in detecting coronary artery stenosis. METHODS: We retrieved PubMed, Cochrane, Embase, and Web of Science until April 11, 2023. The risk of bias in the included studies was appraised using the QUADAS-2 tool. We extracted the accuracy of deep learning in the test set and performed subgroup analyses by binary and multiclass classification scenarios. We performed a subgroup analysis based on different degrees of stenosis and applied a double arcsine transformation to process the data. The analysis was done by using R. RESULTS: Our systematic review finally included 18 studies, involving 3568 patients and 13,362 images. In the included studies, deep learning models were constructed based on CAG and CCTA. In binary classification tasks, the accuracy for detecting > 25%, > 50% and > 70% degrees of stenosis at the vessel level were 0.81 (95% CI: 0.71-0.85), 0.73 (95% CI: 0.58-0.88) and 0.61 (95% CI: 0.56-0.65), respectively. In multiclass classification tasks, the accuracy for detecting 0-25%, 25-50%, 50-70%, and 70-100% degrees of stenosis at the vessel level were 0.78 (95% CI: 0.73-0.84), 0.86 (95% CI: 0.78-0.93), 0.83 (95% CI: 0.70-0.97), and 0.70 (95% CI: 0.42-0.98), respectively. CONCLUSIONS: Our study shows that deep learning models based on CAG and CCTA appear to be relatively accurate in diagnosing different degrees of coronary artery stenosis. However, for various degrees of stenosis, their accuracy still needs to be further improved.

Association between changes of frailty status/frailty components status and rapid loss of kidney function in middle- aged and older populations.

BACKGROUND: Frailty and its components are proposed to associate with kidney function, but little attention is paid to the significance of changes in their status on rapid loss of kidney function. This study aimed to investigate the association between changes in frailty and its components status with rapid loss of renal function. METHODS: This study used data from China Health and Retirement Longitudinal Study (CHARLS). Frailty status was measured using the Fried frailty phenotype (FP) scale, including five components: slowness, weakness, exhaustion, inactivity, and shrinking. Frailty status was further classified into three levels: robust (0 component), prefrail (1-2 components) and frail (3-5 components). Changes in frailty status were assessed by frailty status at baseline and 4- year follow-up. Rapid loss of kidney function was defined as a rate of estimate glomerular filtration rate(eGFR) decline ≥ 4 ml/min per 1.73 m2per year. Logistic regression models were performed to assess the association between changes in frailty status and its components status with rapid eGFR decline. RESULTS: A total of 2705 participants were included with 316 (11.68%) participants categorized as rapid eGFR decline during the 4-year follow-up. Compared with baseline prefrail participants who progressed to frail, prefrail participants who maintained prefrail or recovered to robust status had decreased risks of rapid eGFR decline (stable prefrail status, OR = 0.608, 95% CI: 0.396-0.953; recover to robust, OR = 0.476, 95% CI: 0.266-0.846). In contrast, among baseline robust or frail participants, we did not find changes in frailty status significantly affect the risks of rapid loss of kidney function. Moreover, participants who experienced incident weakness showed the significant relationship with an increased risk of rapid eGFR decline (OR = 1.531, 95% CI: 1.051-2.198) compared to stable non-weakness participants. Other changes of frailty components status did not significantly affect the risks of rapid eGFR decline. CONCLUSIONS: The progression of frailty status increases the risks of rapid eGFR decline among prefrail populations. Preventing weakness, may benefit kidney function.