Apolipoprotein A-1 downregulation promotes basal-like breast cancer cell proliferation and migration associated with DNA methylation.

Apolipoprotein A-I (APOA1) performs different roles in different subtypes of breast cancer. It is hypothesized to function as a tumor suppressor in basal-like breast cancer (BLBC). However, the specific role of APOA1 in BLBC and its underlying mechanisms remain unknown. The findings of the present study demonstrated a positive correlation between the expression level of APOA1 and the overall survival of patients with BLBC. Ectopic expression of APOA1 effectively inhibits the proliferation and metastasis of BLBC cells in vitro, and these effects are closely related to DNA methylation. To the best of our knowledge, the present study is the first to report increased methylation of the promoter region and decreased methylation of the structural genes of APOA1 in BLBC cells. These alterations resulted in the downregulation of APOA1 expression and suppression of BLBC tumor growth. Collectively, the results of the present study suggested that APOA1 mRNA expression is negatively regulated by DNA methylation in BLBC. Therefore, low expression of APOA1 may be a potential risk biomarker to predict survival in patients with BLBC.

Disparities in quality of life among patients with breast cancer based on surgical methods: a cross-sectional prospective study.

To determine the impact of breast conservation on quality of life and identify treatment-related and other demographic factors associated with post-breast cancer treatment quality of life. A prospective study was conducted on 392 women who underwent breast cancer surgery at Hangzhou Cancer Hospital from January 1, 2013, to December 31, 2022. Operable breast cancer patients who had completed all treatments except endocrine therapy were included. Patients with tumor recurrence/metastasis, bilateral or male breast cancer, and other primary malignancies were excluded. After enrollment, patients were asked to complete the BREAST-Q scale, and their pathological and medical records were reviewed. Analysis of variance was used to compare the quality of life scores among the groups. Univariate and multivariate linear regression analyses were performed to identify independent factors associated with quality of life scores in different domains. Participants completed the BREAST-Q scale at a median of 4.6 years after surgery. Quality of life scores varied based on the therapeutic strategy. Breast conservation has significant advantages over mastectomy in terms of breast satisfaction, psychosocial, and sexual well-being. Compared to oncoplastic breast-conserving surgery, mastectomy was independently associated with decreased breast satisfaction, psychosocial, and sexual well-being, while conventional breast-conserving surgery showed comparable outcomes to oncoplastic breast-conserving surgery in terms of these factors. Breast conservation leads to an improvement in quality of life compared to mastectomy. Oncoplastic breast-conserving surgery does not lead to a decrease in quality of life compared to conventional breast-conserving surgery and offers better outcomes compared to mastectomy.

Potential of metallurgical iron-containing solid waste-based catalysts as activator of persulfate for organic pollutants degradation.

The production of solid wastes in the metallurgical industry has significant implications for land resources and environmental pollution. To address this issue, it is crucial to explore the potential of recycling these solid wastes to reduce land occupation while protecting the environment and promoting resource utilization. Steel slag, red mud, copper slag and steel picking waste liquor are examples of solid wastes generated during the metallurgical process that possess high iron content and Fe species, making them excellent catalysts for persulfate-based advanced oxidation processes (PS-AOPs). This review elucidates the catalytic mechanisms and pathways of Fe2+ and Fe0 in the activation PS. Additionally, it underscores the potential of metallurgical iron-containing solid waste (MISW) as a catalyst for PS activation, offering a viable strategy for its high-value utilization. Lastly, the article provides an outlook towards future challenges and prospects for MISW in PS activation for the degradation of organic pollutants.

Bulk RNA-sequencing, single-cell RNA-sequencing analysis, and experimental validation reveal iron metabolism-related genes CISD2 and CYP17A1 are potential diagnostic markers for recurrent pregnancy loss.

BACKGROUND: Recurrent pregnancy loss (RPL) is associated with variable causes. Its etiology remains unexplained in about half of the cases, with no effective treatment available. Individuals with RPL have an irregular iron metabolism. In the present study, we identified key genes impacting iron metabolism that could be used for diagnosing and treating RPL. METHODS: We obtained gene expression profiles from the Gene Expression Omnibus (GEO) database. The Molecular Signatures Database was used to identify 14 gene sets related to iron metabolism, comprising 520 iron metabolism genes. Differential analysis and a weighted gene co-expression network analysis (WGCNA) of gene expression revealed two iron metabolism-related hub genes. Reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry were used on clinical samples to confirm our results. The receiver operating characteristic (ROC) analysis and immune infiltration analysis were conducted. In addition, we analyzed the distribution of genes and performed CellChat analysis by single-cell RNA sequencing. RESULTS: The expression of two hub genes, namely, CDGSH iron sulfur domain 2 (CISD2)and Cytochrome P450 family 17 subfamily A member 1 (CYP17A1), were reduced in RPL, as verified by both qPCR and immunohistochemistry. The Gene Ontology (GO) analysis revealed the genes predominantly engaged in autophagy and iron metabolism. The area under the curve (AUC) demonstrated better diagnostic performance for RPL using CISD2 and CYP17A1. The single-cell transcriptomic analysis of RPL demonstrated that CISD2 is expressed in the majority of cell subpopulations, whereas CYP17A1 is not. The cell cycle analysis revealed highly active natural killer (NK) cells that displayed the highest communications with other cells, including the strongest interaction with macrophages through the migratory inhibitory factor (MIF) pathway. CONCLUSIONS: Our study suggested that CISD2 and CYP17A1 genes are involved in abnormal iron metabolism, thereby contributing to RPL. These genes could be used as potential diagnostic and therapeutic markers for RPL.

m5 C regulator-mediated methylation modification patterns and tumor microenvironment infiltration characteristics in acute myeloid leukemia.

BACKGROUND: Recently, many studies have been conducted to examine immune response modification at epigenetic level, but the candidate effect of RNA 5-methylcytosine (m5 C) modification on tumor microenvironment (TME) of acute myeloid leukemia (AML) is still unknown at present. METHODS: We assessed the patterns of m5 C modification among 417 AML cases by using nine m5 C regulators. Thereafter, we associated those identified modification patterns with TME cell infiltration features. Additionally, stepwise regression and LASSO Cox regression analyses were conducted for quantifying patterns of m5 C modification among AML cases to establish the m5 C-score. Meanwhile, we validated the expression of genes in the m5C-score model by qRT-PCR. Finally, the present work analyzed the association between m5 C-score and AML clinical characteristics and prognostic outcomes. RESULTS: In total, three different patterns of m5 C modification (m5 C-clusters) were identified, and highly differentiated TME cell infiltration features were also identified. On this basis, evaluating patterns of m5 C modification in single cancer samples was important for evaluating the immune/stromal activities in TME and for predicting prognosis. In addition, the m5 C-score was established, which showed a close relation with the overall survival (OS) of test and training set samples. Moreover, multivariate Cox analysis suggested that our constructed m5 C-score served as the independent predicting factor for the prognosis of AML (hazard ratio = 1.57, 95% confidence interval = 1.38-1.79, p < 1e-5 ). CONCLUSIONS: This study shows that m5 C modification may be one of the key roles in the formation of diversity and complexity of TME. Meanwhile, assessing the patterns of m5 C modification among individual cancer samples is of great importance, which provides insights into cell infiltration features within TME, thereby helping to develop relevant immunotherapy and predict patient prognostic outcomes.

The earliest optimal timing for total-body 68Ga-fibroblast activation protein inhibitor-04 PET scans: an evidence-based single-centre study.

OBJECTIVES: To investigate the earliest optimal timing for positron emission tomography (PET) scans after 68Ga-fibroblast activation protein inhibitor-04 ([68Ga]Ga-FAPI-04) injection. METHODS: This prospective study enrolled patients who underwent 60-min dynamic 68Ga-FAPI-04 total-body PET/CT scans; the images were reconstructed at 10-min intervals (G0-10, G10-20, G20-30, G30-40, G40-50, and G50-60), and the [68Ga]Ga-FAPI-04 uptake patterns were evaluated. The standardised uptake value (SUV), liver signal-to-noise ratio (SNR), and lesion-to-background ratios (LBRs) for different time windows were calculated to evaluate image quality and lesion detectability. The period from 30 to 40 min was then split into overlapping 5-min intervals starting 1 min apart for further evaluation. G50-60 was considered the reference. RESULTS: A total of 30 patients with suspected malignant tumours were analysed. In the images reconstructed over 10-min intervals, longer acquisition times were associated with lower background uptake and better image quality. Some lesions could not be detected until G30-40. The lesion detection rate, uptake, and LBRs did not differ significantly among G30-40, G40-50, and G50-60 (all p > 0.05). The SUVmean and LBRs of primary tumours in the reconstructed images did not differ significantly among the 5-min intervals between 30 and 40 min; for metastatic and benign lesions, G34-39 and G35-40 showed significantly better SUVmean and LBR values than the other images. The G34-39 and G50-60 scans showed no significant differences in uptake, LBRs, or detection rates (all p > 0.05). CONCLUSION: The earliest optimal time to start acquisition was 34 min after injection of half-dose [68Ga]Ga-FAPI-04. CLINICAL RELEVANCE STATEMENT: This study evaluated 68Ga-fibroblast activation protein inhibitor-04 ([68Ga]Ga-FAPI-04) uptake patterns by comparing the image quality and lesion detection rate with 60-min dynamic [68Ga]Ga-FAPI-04 total-body PET/CT scans and identified the earliest optimal scan time after [68Ga]Ga-FAPI-04 injection. KEY POINTS: • A prospective single-centre study showed that the earliest optimal time point to start acquisition was 34 min after injection of half-dose [68Ga-fibroblast activation protein inhibitor-04 (68Ga]Ga-FAPI-04). • There were statistically significant differences in standardised uptake value, lesion-to-background ratios, and lesion detectability between scans before and after 34 min from the injection of [68Ga]Ga-FAPI-04, but these values did not change further from 34 to 60 min after injection. • With a reasonable acquisition time, the image quality could still meet diagnostic requirements.

Relationship between stress hyperglycemia and worsening heart failure in patients with significant secondary mitral regurgitation.

BACKGROUND AND AIMS: Secondary mitral regurgitation (sMR), a major valvular disease, is prevalent in patients with coronary artery disease (CAD), and is associated with higher incidence of heart failure (HF) and mortality when present in combination with abnormal glucose metabolism. We aimed to evaluate the relationship between stress hyperglycemia ratio (SHR) and worsening HF in CAD patients with significant (grade ≥2) sMR. METHODS: We performed a multi-center observational study of 874 participants with significant sMR following percutaneous coronary intervention (PCI) in the Cardiorenal Improvement-II (CIN-II) cohort. Patients with glucose and glycated hemoglobin (HbA1c) data at admission were included in the analysis, and categorized according to the SHR, the ratio of mmol/L blood glucose to % HbA1c, as quartiles: Q1: <0.74; Q2: 0.74-0.91; Q3: 0.91-1.14; and Q4: ≥1.14. The primary clinical endpoint was worsening HF and the secondary endpoint was major adverse cardiac events (MACE). RESULTS: Of the 874 participants (64.1 ± 10.8 years, 80% male), 174 showed worsening HF and 226 developed MACE during a median follow-up of 3.7 years (interquartile range: 1.8-6.2 years). Compared to participants in the lowest quartile (Q1) of SHR, the highest quartile group (Q4) was at significantly higher risks of worsening HF (adjusted hazard ratio, 2.44; 95% confidence interval, 1.51-3.94; p< 0.001), while this was not associated with increased risk of MACE (p>0.05) after adjustment for potential covariates. For worsening HF, the results obtained for the normal glucose regulation subgroup may be more meaningful than those for the diabetes mellitus (DM) and pre-DM groups (p-interaction<0.001). For MACE, the acute myocardial infarction (AMI) (Q4 vs. Q1; HR: 0.65, 95%CI: 0.26-1.59) and non-AMI (Q4 vs. Q1; HR: 2.20, 95%CI: 1.36-3.54) subgroups differed significantly on MACE (p-interaction = 0.006). CONCLUSIONS: Increasing SHR is associated with a higher risk of worsening of HF in patients with significant sMR, especially in those with normoglycemia.

Study on Erosion Behavior of Laser Wire Feeding Cladding High-Manganese Steel Coatings.

High-manganese steel (HMnS) coating was prepared using laser wire feeding cladding technology. Erosion damage behavior and erosion rate of both the HMnS coating and the HMnS substrate were investigated at room temperature using an erosion testing machine. SEM/EDS, XRD, EPMA, and microhardness analyses were used to characterize the cross sections of the coating and matrix, as well as the morphology, phase composition, and microhardness of the eroded surface. The phase composition, orientation characteristics, and grain size of the eroded surfaces of both the coating and substrate were examined by using the EBSD technique. The erosion mechanism under different erosion angles was revealed. By analyzing the plastic deformation behavior of the subsurface of the HMnS coating, the impact hardening mechanism of the high-manganese steel coating during the erosion process was investigated. The results demonstrated that the HMnS coating, prepared through laser wire feeding cladding, exhibited excellent metallurgical bonding with the substrate, featuring a dense microstructure without any cracks. The erosion rate of the coatings was lower than that of the substrate at different erosion angles, with the maximum erosion rate occurring at 35° and 50°. The damage to the coating and substrate under low-angle erosion was primarily attributed to the micro-cutting of erosion particles and a minor amount of hammering. At the 90° angle, the dominant factor was hammering. After erosion, the microhardness of both the coating and substrate sublayer increased to 380HV0.3 and 359HV0.3, respectively. Dendrite segregation, refined grains, low-angle grain boundaries, and localized dislocations, generated by laser wire feeding cladding, contributed to the deformation process of HMnS. These factors collectively enhance the hardening behavior of HMnS coatings, thereby providing excellent erosion resistance.

Head-to-head intra-individual comparison of total-body 2-[18F]FDG PET/CT and digital PET/CT in patients with malignant tumor: how sensitive could it be?

OBJECTIVES: To comparatively evaluate the lesion-detecting ability of 2-[18F]FDG total-body PET/CT (TB PET/CT) and conventional digital PET/CT. METHODS: This study enrolled 67 patients (median age, 65 years; 24 female and 43 male patients) who underwent a TB PET/CT scan and a conventional digital PET/CT scan after a single 2-[18F]FDG injection (3.7 MBq/kg). Raw PET data for TB PET/CT were acquired over the course of 5 min, and images were reconstructed using data from the first 1, 2, 3, and 4 min and the entire 5 min (G1, G2, G3, G4, and G5, respectively). The conventional digital PET/CT scan acquired in 2-3 min per bed (G0). Two nuclear medicine physicians independently assessed subjective image quality using a 5-point Likert scale and recorded the number of 2-[18F]FDG-avid lesions. RESULTS: A total of 241 lesions (69 primary lesions; 32 liver, lung, and peritoneum metastases; and 140 regional lymph nodes) among 67 patients with various types of cancer were analyzed. The subjective image quality score and SNR (signal-to-noise ratio) increased gradually from G1 to G5, and these values were significantly higher than the values at G0 (all p < 0.05). Compared to conventional PET/CT, G4 and G5 of TB PET/CT detected an additional 15 lesions (2 primary lesions; 5 liver, lung, and peritoneum lesions; and 8 lymph node metastases). CONCLUSION: TB PET/CT was more sensitive than conventional whole-body PET/CT in detecting small (4.3 mm, maximum standardized uptake value (SUVmax) of 1.0) or low-uptake (tumor-to-liver ratio of 1.6, SUVmax of 4.1) lesions. CLINICAL RELEVANCE STATEMENT: This study explored the gain of the image quality and lesion detectability of TB PET/CT, compared to conventional PET/CT, and recommended the appropriate acquisition time for TB PET/CT in clinical practice with an ordinary 2-[18F] FDG dose. KEY POINTS: • TB PET/CT increases the effective sensitivity to approximately 40 times that of conventional PET scanners. • The subjective image quality score and signal-to-noise ratio of TB PET/CT from G1 to G5 were better than those of conventional PET/CT. • 2-[18F]FDG TB PET/CT with a 4-min acquisition time at a regular tracer dose detected an additional 15 lesions compared to conventional PET/CT.

Realizing of ZSM-5 microspheres with enhanced catalytic properties prepared from iron ore tailings via solid-phase conversion method.

The comprehensive utilization of iron ore tailings (IOTs) not only resolved environmental problems but also brought huge economic benefits. In this study, the synthetic route presented herein provides a novel method for the synthesis of ZSM-5 microspheres from IOTs. The effects of Si/Al molar ratios and the pH of the precursor solution on the formation of zeolite was evaluated by various analytical methods. The catalytic performance of the catalyst prepared by the solid-phase conversion method (denoted as MP-ZSM-5) was evaluated by methanol-to-propylene (MTP) reaction. Compared with the zeolite catalyst that synthesized via the conventional hydrothermal method (denoted as HM-ZSM-5), MP-ZSM-5 not only prolongs catalytic lifetime from 18.7 to 36.0 h but also has higher selectivity for propylene by MP-ZSM-5 (43.7%) than that for HM-ZSM-5 (38.6%). In addition, Kissinger-Akahira-Sunose (KAS) model is applied to the TG result to study the template removal process kinetics. The average activation energy values required for the removal of CTAB and TPABr are 201.11 ± 13.42 and 326.88 ± 16.91 kJ∙mol-1, respectively. Furthermore, this result is well coupled with the model-free kinetic algorithms to determine the conversion and isoconversion of the TPABr and CTAB decomposition in ZSM-5, which serves as important guidelines for the industrial production process.

Association of malnutrition with all-cause and cardiovascular mortality in patients with mild to severe chronic kidney disease undergoing coronary angiography: a large multicenter longitudinal study.

PURPOSE: Evidence on the prognostic impact of malnutrition was focused on patients with advanced kidney disease. The relationships between malnutrition and all-cause and cardiovascular mortality in patients with different severity of chronic kidney disease (CKD) have not been adequately addressed. We aimed to reveal the prevalence of malnutrition and its prognostic value in patients with different severity of CKD undergoing coronary angiography (CAG). METHODS: This was a multicenter, longitudinal, and retrospective cohort study of 12,652 patients with non-dialysis dependent CKD (defined as estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2) undergoing CAG from five tertiary hospitals between January 2007 and December 2020. The controlling nutritional status (CONUT) score was applied to assess nutritional status. Cox regression models and competing risk Fine and Gray models were used to examine the relationships between malnutrition, all-cause and cardiovascular mortality. Further stratified analysis was performed according to baseline CKD severity (mild, moderate and severe, defined by eGFR < 30, 30-44 and 45-59 ml/min/1.73 m2). RESULTS: During a median follow-up of 5.5 years (interquartile range: 3.2 to 8.6 years), 3801 patients (30.0%) died, and 2150 (17.0%) definitely died of cardiovascular disease. After controlling for confounders, patients had higher all-cause mortality (mild, moderate, and severe vs. absent: HR 1.27, 95 CI % [1.17-1.39]; HR 1.54, 95 CI % [1.39-1.71]; HR 2.22, 95 CI % [1.78-2.77], respectively; P for trend < 0.001) and cardiovascular mortality (mild, moderate and severe vs. absent: HR 1.35, 95 CI % [1.21-1.52]; HR 1.67, 95 CI % [1.45-1.92]; HR 2.10, 95 CI % [1.55-2.85], respectively; P for trend < 0.001) with the severity of malnutrition. In further stratified analysis, a similar prognostic impact of malnutrition was observed in patients with mild to moderate CKD, while mild malnutrition did not seem to have a consistent effect on severe CKD patients. CONCLUSION: Malnutrition is common among patients with mild to severe CKD undergoing CAG and is strongly associated with increased risk of all-cause and cardiovascular mortality. Malnutrition seems to have a modestly stronger impact on mortality in patients with mild to moderate CKD. This study was registered at Clinicaltrials.gov as NCT05050877.

Lateral thoracic adipofascial flaps in the reconstruction of defects after breast-conserving surgery in breasts with ptosis mild ptosis or without ptosis.

OBJECTIVE: To study the feasibility, safety, and effectiveness of lateral thoracic adipofascial flaps in reconstructing the defects following breast-conserving surgery (BCS) in breasts with either no ptosis or mild ptosis. METHODS: 37 female patients who underwent BCS and lateral thoracic adipofascial flap breast reconstruction between June 2020 and July 2022 were analysed. Surgery-related complications, intraoperative positive margin, local recurrence, and cosmetic outcome were assessed. RESULTS: Three local complications occurred in patients, all of which were cured by conservative treatment. Additionally, four patients had intraoperative positive margins. After a median follow-up period of 17.5 months, none of the patients showed local recurrence. All patients achieved a satisfactory breast shape. Further, patients without ptosis achieved good volume and symmetry. However, the breast symmetry was not satisfactory for patients with ptosis. CONCLUSION: It is reliable and effective to use the lateral thoracic adipofascial flaps to reconstruct the defects after BCS when the breast is not ptotic and the lesions are located in the lateral and central quadrants.

KMT2D Regulates the NCOA6/THRB Signal Axis through Epigenetic Modification to Promote the Migration and Invasion of Papillary Thyroid Cancer.

BACKGROUND: The histone lysine methyltransferase Histone-lysine N-methytransferase 2D (KMT2D) is a common mutated gene in a variety of cancers, including papillary thyroid cancer (PTC). However, the mechanism of KMT2D on the progression of PTC remains unclear. METHODS: In this study, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to evaluate KMT2D expression between human normal cell (Nthy-ori 3-1) and PTC cells (TPC1, IHH-4 and BCPAP). Proliferation, migration and invasion of TPC1, IHH-4 and BCPAP were assessed by Cell Counting Kit-8 (CCK-8), Wound-healing assay and Transwell assay. The mechanism of KMT2D on thyroid papillary cancer was explored with Chromatin immunoprecipitation assay (ChIP), qRT-PCR and Western blotting. RESULTS: The expression of KMT2D in PTC cells was significantly increased. Downregulation of KMT2D significantly decreased the proliferation, migration and invasion of PTC cells, which was correlated with decreased expression levels of H3K4me2, H3K9me2, NCOA6 and THRB. Meanwhile, ChIP assay demonstrated that KMT2D was associated with NCOA6. CONCLUSIONS: Study have shown that the downregulation of KMT2D reduces proliferation, migration and invasion of thyroid papillary carcinoma cells through epigenetic modification of NCOA6/THRB signal axis. These results provide a new insight into the role of KMT2D in migration and invasion of PTC.

Association of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and acute kidney disease in patients undergoing coronary angiography: a cohort study.

BACKGROUND: Acute kidney disease (AKD) following coronary angiography (CAG) indicates a higher risk of chronic kidney disease and follow-up cardiovascular comorbidities. However, the predictive risk factor of AKD is not clear. We sought to verify whether preoperative N-terminal pro-B-type natriuretic peptide (NT-proBNP) level was associated with AKD in patients undergoing CAG. METHOD: We analyzed 7602 patients underwent CAG in this multi-center registry cohort study. Cardiorenal ImprovemeNt II (CIN-II) in five Chinese tertiary hospitals from 2007 to 2020. The primary outcome was AKD, defined as a ≥ 50% increase of serum creatinine within 7-90 days. Multivariable logistic regressions were used to assess the association between NT-proBNP and AKD. RESULT: 1009 patients (13.27%) eventually developed AKD, who were more likely to be female, older, and with comorbidities of chronic heart failure and anemia. After adjusting to the potential confounders, the NT-proBNP level remained an independent predictor of AKD (lnNT-proBNP OR: 1.20, 95% CI 1.13-1.28, p < 0.005). Restricted cubic spline analysis demonstrated a linear relationship between elevated NT-proBNP and AKD (p for trend < 0.001). In the subgroup analysis, elevated NT-proBNP level in patients with percutaneous coronary intervention (p for interaction < 0.001) or without previous congestive heart failure (p for interaction = 0.0346) has a more significant value of AKD prediction. CONCLUSION: Pre-operative NT-proBNP level was independently associated with the risk of AKD in patients following CAG. Perioperative strategies are warranted to prevent AKD in patients with elevated NT-proBNP levels.

Association between triglyceride glucose index and worsening heart failure in significant secondary mitral regurgitation following percutaneous coronary intervention.

BACKGROUND: The triglyceride glucose (TyG) index is an alternative to insulin resistance (IR) as an early indicator of worsening heart failure (HF). Patients with secondary mitral regurgitation (sMR) often experience progressive deterioration of cardiac function. This study aimed to investigate the relationship between the TyG index and worsening of HF in significant sMR (grade ≥ 2) following percutaneous coronary intervention (PCI). METHODS: This study enrolled participants with significant sMR following PCI from a multicenter cohort study. The patients were divided into the following 3 groups according to tertiles of TyG index: T1, TyG ≤ 8.51; T2, TyG > 8.51 to ≤ 8.98; and T3, TyG > 8.98. The main clinical outcome was worsening HF including unplanned rehospitalization or unscheduled physician office/emergency department visit due to HF and unplanned mitral valve surgery. RESULTS: A total of 922 patients (mean ± SD age, 64.1 ± 11.0 years; 79.6% male) were enrolled. The incidence of worsening HF was 15.5% in T1, 15.7% in T2, and 26.4% in T3. In the multivariable model, the highest TyG tertile (T3 group) was more strongly correlated with worsening HF than the lowest tertile (T1 group) after adjusting for confounders (adjusted hazard ratio, 2.44; 95% confidence interval, 1.59-3.72; P < 0.001). The addition of TyG to risk factors such as N-terminal pro brain natriuretic peptide and clinical models improved the predictive ability of TyG for worsening HF. CONCLUSIONS: Elevated preprocedural TyG index is a significant and independent risk factor for worsening HF in sMR following PCI that can be used for risk stratification.

MAP7 Promotes Breast Cancer Cell Migration and Invasion by Regulating the NF-B Pathway.

OBJECTIVE: To investigate and explore the molecular mechanisms of MAP7 on breast cancer cell migration and invasion. METHODS: The MAP7 transcript data in TCGA database was firstly statistically analyzed. Then, immunohistochemistry and western blot assays were applied to check MAP7 expression levels in breast cancer tissues or cell lines. EdU immunofluorescent staining assay was applied to reveal the cell proliferation of breast cancer cells after knockdown or overexpression of MAP7. Scratch and Transwell assays were applied to observe cell invasion and migration after knockdown or overexpression of MAP7. The western blot assays were employed to prove the expression levels of NF-B p65 and IBα after knockdown or overexpression of MAP7. Finally, breast xenograft model was established to verify the tumor volume and weight in mice. RESULTS: The results indicated the mRNA and protein expression of MAP7 was higher in breast cancer tissues or cell lines than that in normal tissue or normal breast epithelial cells, respectively. MAP7 promoted proliferation, migration, and invasion of breast cancer cells. Knockdown or overexpression of MAP7 in breast cancer cells would inhibit or promote phosphorylation of NF-B p65 and IBα protein. Finally, MAP7 can also promote tumor growth in mice. CONCLUSIONS: MAP7 facilitated breast cancer cell migration and invasion by regulating the NF-B pathway.

Necroptosis-associated long noncoding RNAs can predict prognosis and differentiate between cold and hot tumors in ovarian cancer.

Objective: The mortality rate of ovarian cancer (OC) is the highest among all gynecologic cancers. To predict the prognosis and the efficacy of immunotherapy, we identified new biomarkers. Methods: The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression Project (GTEx) databases were used to extract ovarian cancer transcriptomes. By performing the co-expression analysis, we identified necroptosis-associated long noncoding RNAs (lncRNAs). We used the least absolute shrinkage and selection operator (LASSO) to build the risk model. The qRT-PCR assay was conducted to confirm the differential expression of lncRNAs in the ovarian cancer cell line SK-OV-3. Gene Set Enrichment Analysis, Kaplan-Meier analysis, and the nomogram were used to determine the lncRNAs model. Additionally, the risk model was estimated to evaluate the efficacy of immunotherapy and chemotherapy. We classified necroptosis-associated IncRNAs into two clusters to distinguish between cold and hot tumors. Results: The model was constructed using six necroptosis-associated lncRNAs. The calibration plots from the model showed good consistency with the prognostic predictions. The overall survival of one, three, and five-year areas under the ROC curve (AUC) was 0.691, 0.678, and 0.691, respectively. There were significant differences in the IC50 between the risk groups, which could serve as a guide to systemic treatment. The results of the qRT-PCR assay showed that AL928654.1, AL133371.2, AC007991.4, and LINC00996 were significantly higher in the SK-OV-3 cell line than in the Iose-80 cell line (P < 0.05). The clusters could be applied to differentiate between cold and hot tumors more accurately and assist in accurate mediation. Cluster 2 was more vulnerable to immunotherapies and was identified as the hot tumor. Conclusion: Necroptosis-associated lncRNAs are reliable predictors of prognosis and can provide a treatment strategy by screening for hot tumors.

Optimizing acquisition times for total-body positron emission tomography/computed tomography with half-dose 18F-fluorodeoxyglucose in oncology patients.

BACKGROUND: The present study aimed to explore the boundary of acquisition time and propose an optimized acquisition time range for total-body positron emission tomography (PET)/computed tomography (CT) oncological imaging using half-dose (1.85 MBq/kg) 18F-fluorodeoxyglucose activity based on diagnostic needs. METHODS: In this retrospective study based on a total-body PET system (uEXPLORER), an exploration cohort (October 2019-December 2019) of 46 oncology patients was first studied. The acquisition time for all patients was 15 min, and the acquired images were reconstructed and further split into 15-, 8-, 5-, 3-, 2-, and 1-min duration groups (abbreviated as G15, G8, G5, G3, G2, and G1). The image quality and lesion detectability of reconstructed PET images with different acquisition times were evaluated subjectively (5-point scale, lesion detection rate) and objectively (standardized uptake values, tumor-to-background ratio). In the same way, the initial optimized acquisition times were further validated in a cohort of 147 oncology patients (December 2019-June 2021) by using the Gs images (the images obtained using the 15- and 10-min acquisition times) as controls. RESULTS: In the exploration cohort, the subjective scores for G1, G2, G3, G5, and G8 images were 2.0 ± 0.2, 2.9 ± 0.3, 3.0 ± 0.0, 3.9 ± 0.2, and 4.2 ± 0.4, respectively. Two cases in G1 were rated as 1 point. No significant difference in scores was observed between G5 and G8 (p > 0.99). In general, groups with a longer acquisition time showed lower background uptake and lesion conspicuity. Compared with G15, lesion detection rate significantly reduced to 85.3% in G1 (p < 0.05). In the validation cohort, the subjective score was 3.0 ± 0.2 for G2, 3.0 ± 0.1 for G3, 3.6 ± 0.5 for G5, 4.0 ± 0.3 for G8, and 4.4 ± 0.5 for Gs. Only the scores between G2 and G3 were not significantly different (p > 0.99). The detection rates (204 lesions) significantly reduced to 94.1-90.2% in G3 and G2 (all p < 0.05). CONCLUSION: A 2-min acquisition time provided acceptable performance in certain groups and specific medical situations. And protocols with acquisition times ≥ 5 min could provide comparable lesion detectability as regular protocols, showing better compatibility and feasibility with clinical practice.

circNup188/miR-760-3p/Map3k8 axis regulates inflammation in cerebral ischemia.

INTRODUCTION: Cerebral ischemia is a serious acute disease with high mortality and disability rates. circRNAs are associated with cerebral ischemia inflammation and can be used as therapeutic targets. We aimed to investigate circNup188/miR-760-3p/Map3k8 role in inflammation during cerebral ischemia. METHODS: According to the sequencing results of previously published, signaling pathways and circRNAs related to inflammation were screened and looped for verification. In vitro OGD/R cell model was constructed to detect OGD/R effects on PC12 cell viability, apoptosis, inflammatory cytokines TNF-α, IL-1ß and IL-6. qRT-PCR assessed circRNAs, circNup188 bound miRNAs, and four mRNAs associated with inflammation and brain diseases expressions. p65 and IkB-α and their phosphorylated proteins in NF-κB pathway and Map3k8 expressions were assessed by Western blot. RESULTS: KEGG analysis revealed MAPK and NF-kappaB signaling pathways played a vital role in it, and were classic inflammatory pathways. circNup188, circU2, and circCnot2 were verified to be the loop structure. circNup188 might play an essential role in OGD/R cell model. Regulating circNup188 expression could affect OGD/R cells function. In addition, miR-760-3p might play a vital role in OGD/R cell model. Moreover, circNup188 regulated cerebral ischemia by sponging miR-760-3p. miR-760-3p might be involved in inflammation in OGD/R cell model by regulating Map3k8 to activate the NF-κB pathway. CONCLUSIONS: circNup188 might up-regulate Map3k8 expression through sponging miR-760-3p and then activate NF-κB pathway, which was involved in cerebral ischemia development. This study provided a new target for cerebral ischemia treatment.