Efficiency of different annuloplasty in treating functional tricuspid regurgitation and risk factors for recurrence

AbstractBackgroundFunctional tricuspid regurgitation (FTR) is frequent in patients with mitral valve disease. Untreated tricuspid regurgitation (TR) may cause poor clinical outcomes. The surgical factors involved in annuloplasty for FTR remain controversial. Our objective was to compare effectiveness of different tricuspid annuloplasty (TVP), and reveal the risk factors of recurrence.MethodsWe analyzed the clinical details of 399 consecutive patients who underwent mitral surgery with concomitant TVP, from 2006 to 2011, in two Chinese single-centers. Three methods were used for TVP: De Vega surgery was completed in 242 patients; annuloplasty using a flexible band was completed in 98 patients; and surgery with a rigid ring was performed in 59 patients.ResultsThe operative mortality rate was 2.3%. After surgery, the TR grade of all patients decreased significantly. At three years postoperatively, 13.7% of patients were diagnosed with recurrent FTR. At the three year time point, severe TR in the De Vega group was 18%, which was higher than those in the flexible (8.4%) and rigid planner ring groups (5.2%). During follow-up, the recurrent rates in the rigid group were significantly lower than in the flexible group. Multivariate analysis revealed that pre-operative atrial fibrillation, severe TR, large left atrial, ejection fraction (EF)<40%, De Vega annuloplasty, and postoperative permanent pacemaker installation were independent risk factors for severe recurrent TR.ConclusionsRigid ring annuloplasty efficaciously improved post-operative tricuspid valve function in patients with FTR. Atrial fibrillation, a large left atrium, low EF and postoperative permanent pacemaker installation were independent risk factors for severe recurrent TR

Integrated machine learning identifies a cellular senescence-related prognostic model to improve outcomes in uterine corpus endometrial carcinoma

BackgroundUterine Corpus Endometrial Carcinoma (UCEC) stands as one of the prevalent malignancies impacting women globally. Given its heterogeneous nature, personalized therapeutic approaches are increasingly significant for optimizing patient outcomes. This study investigated the prognostic potential of cellular senescence genes(CSGs) in UCEC, utilizing machine learning techniques integrated with large-scale genomic data.MethodsA comprehensive analysis was conducted using transcriptomic and clinical data from 579 endometrial cancer patients sourced from the Cancer Genome Atlas (TCGA). A subset of 503 CSGs was assessed through weighted gene co-expression network analysis (WGCNA) alongside machine learning algorithms, including Gaussian Mixture Model (GMM), support vector machine - recursive feature elimination (SVM-RFE), Random Forest, and eXtreme Gradient Boosting (XGBoost), to identify key differentially expressed cellular senescence genes. These genes underwent further analysis to construct a prognostic model.ResultsOur analysis revealed two distinct molecular clusters of UCEC with significant differences in tumor microenvironment and survival outcomes. Utilizing cellular senescence genes, a prognostic model effectively stratified patients into high-risk and low-risk categories. Patients in the high-risk group exhibited compromised overall survival and presented distinct molecular and immune profiles indicative of tumor progression. Crucially, the prognostic model demonstrated robust predictive performance and underwent validation in an independent patient cohort.ConclusionThe study emphasized the significance of cellular senescence genes in UCEC progression and underscored the efficacy of machine learning in developing reliable prognostic models. Our findings suggested that targeting cellular senescence holds promise as a strategy in personalized UCEC treatment, thus warranting further clinical investigation

The relationship between neuromyelitis optica spectrum disorder and autoimmune diseases

ObjectiveThere have been reports of neuromyelitis optica spectrum disorder (NMOSD) coexisting with connective tissue disorders. The objective of this study was to describe the characteristics of NMOSD coexisting with autoimmune diseases (AID).MethodsThis retrospective study evaluated NMOSD patients with and without AID. The enrolled patients had at least one attack, with duration of more than 1 year. Data on the demographics, clinical features, and laboratory findings were assessed. The Poisson model was used to investigate the risk factors associated with the annualized relapse rate (ARR), whereas the Cox model was used to evaluate the risk factors for the first relapse.ResultsA total of 180 patients (154 women and 26 men) with NMOSD were identified: 45 had AID and 135 did not. Female patients had a higher prevalence of concomitant AID (p = 0.006) and a greater relapse rate within the first year. There were no statistically significant differences in the characteristics of patients. Kaplan–Meier analysis revealed that NMOSD patients with seropositive aquaporin 4 antibodies (AQP4-Ab; log-rank: p = 0.044), had a shorter time to relapse. Patients seropositive for AQP4-Ab (HR = 2.402, 95%CI = 1.092–5.283, p = 0.029) had a higher risk of suffering a first relapse, according to the Cox model. Patients with and without AID showed a similar declining tendency in terms of change in ARR throughout the first 5 years of the disease. The ARR was greater in the first year [incidence rate ratio (IRR) = 1.534, 95%CI = 1.111–2.118] and the first 2 years (IRR = 1.474, 95%CI = 1.056–2.058) in patients with coexisting AID diagnosis prior to the NMOSD onset.ConclusionsPatients with NMOSD with coexisting AID had similar characteristics when compared with those without AID. NMOSD patients with AID diagnosed before onset had a higher risk of relapse in the early stage of the disease

Research Progress on the Effects of Anthocyanidin Compounds on Physicochemical Properties of Starch

Anthocyanidin compounds include proanthocyanidins, anthocyanidins, anthocyanins, etc. Among them, proanthocyanidin is a kind of polyphenol compound, then anthocyanidin and anthocyanin belong to flavonoid compounds. When heated in an acidic medium, proanthocyanidins can produce anthocyanidins, which combine with sugars via glycosidic bonds to produce anthocyanins. Proanthocyanidins, anthocyanidins and anthocyanins are widely distributed in dark grains, berries and vegetables, all of them have various functional effects. Starch is low in price, rich in sources, and has a variety of functional properties. The sensory quality and nutritional value of starch-based foods are mainly determined by the changes of starch gelatinization properties, thermodynamic properties, rheological properties, aging properties and digestive properties. There have been many studies about the co-existence of starch and other compounds that can improve the original properties of starch. However, there is limited overview on the effects of anthocyanidin compounds on starch properties. Therefore, this paper reviews the latest research progress of anthocyanidin compounds and their effects on the gelatinization properties, thermodynamic properties, rheological properties, aging properties and digestive properties of starch through increasing the gelatinization temperature of starch and reducing its gelatinization enthalpy can affect its thermodynamic properties, as well as reduce its aging enthalpy and aging rate, additionally and the digestion rate of starch etc. These can provide guidance for the use of anthocyandin compounds to improve the processing properties, sensory and nutritional quality of starch-based foods

Mapping of Cu and Pb Contaminations in Soil Using Combined Geochemistry, Topography, and Remote Sensing: A Case Study in the Le’an River Floodplain, China

Heavy metal pollution in soil is becoming a widely concerning environmental problem in China. The aim of this study is to integrate multiple sources of data, namely total Cu and Pb contents, digital elevation model (DEM) data, remote sensing image and interpreted land-use data, for mapping the spatial distribution of total Cu and Pb contamination in top soil along the Le’an River and its branches. Combined with geographical analyses and watershed delineation, the source and transportation route of pollutants are identified. Regions at high risk of Cu or Pb pollution are suggested. Results reveal that topography is the major factor that controls the spatial distribution of Cu and Pb. Watershed delineation shows evidence that the streamflow resulting from rainfall is the major carrier of metal pollutants

Presynaptic density determined by SV2A PET is closely associated with postsynaptic metabotropic glutamate receptor 5 availability and independent of amyloid pathology in early cognitive impairment

INTRODUCTION: Metabotropic glutamate receptor 5 (mGluR5) is involved in regulating integrative brain function and synaptic transmission. Aberrant mGluR5 signaling and relevant synaptic failure play a key role in the pathophysiological mechanism of Alzheimer's disease (AD). METHODS: Ten cognitively impaired (CI) individuals and 10 healthy controls (HCs) underwent 18FSynVesT-1 and 18FPSS232 positron emission tomography (PET)/magnetic resonance to assess synaptic density and mGluR5 availability. The associations between mGluR5 availability and synaptic density were examined. A mediation analysis was performed to investigate the possible mediating effects of mGluR5 availability and synaptic loss on the relationship between amyloid deposition and cognition. RESULTS: CI patients exhibited lower mGluR5 availability and synaptic density in the medial temporal lobe than HCs. Regional synaptic density was closely associated with regional mGluR5 availability. mGluR5 availability and synaptic loss partially mediated the relationship between amyloid deposition and cognition. CONCLUSIONS: Reductions in mGluR5 availability and synaptic density exhibit similar spatial patterns in AD and are closely linked. Highlights - Cognitively impaired patients exhibited lower mGluR5 availability and synaptic density in the medial temporal lobe than HCs. - Reductions in mGluR5 availability and synaptic density exhibit similar spatial patterns in AD. - Regional synaptic density was closely associated with regional mGluR5 availability. - mGluR5 availability and synaptic loss partially mediated the relationship between amyloid deposition and global cognition. - With further research, modulating mGluR5 availability might be a potential therapeutic strategy for improving synaptic function in AD

Oncogenic KRAS Drives Lipofibrogenesis to Promote Angiogenesis and Colon Cancer Progression

Oncogenic KRAS (KRAS*) contributes to many cancer hallmarks. In colorectal cancer, KRAS* suppresses antitumor immunity to promote tumor invasion and metastasis. Here, we uncovered that KRAS* transforms the phenotype of carcinoma-associated fibroblasts (CAF) into lipid-laden CAFs, promoting angiogenesis and tumor progression. Mechanistically, KRAS* activates the transcription factor CP2 (TFCP2) that upregulates the expression of the proadipogenic factors BMP4 and WNT5B, triggering the transformation of CAFs into lipid-rich CAFs. These lipid-rich CAFs, in turn, produce VEGFA to spur angiogenesis. In KRAS*-driven colorectal cancer mouse models, genetic or pharmacologic neutralization of TFCP2 reduced lipid-rich CAFs, lessened tumor angiogenesis, and improved overall survival. Correspondingly, in human colorectal cancer, lipid-rich CAF and TFCP2 signatures correlate with worse prognosis. This work unveils a new role for KRAS* in transforming CAFs, driving tumor angiogenesis and disease progression, providing an actionable therapeutic intervention for KRAS*-driven colorectal cancer

Elevated Brain Cannabinoid CB1 Receptor Availability in Posttraumatic Stress Disorder: A Positron Emission Tomography Study

Endocannabinoids and their attending cannabinoid type 1 receptor (CB1) have been implicated in animal models of posttraumatic stress disorder (PTSD). However, their specific role has not been studied in people with PTSD. Herein, we present an in vivo imaging study using positron emission tomography (PET) and the CB1-selective radioligand [11C]OMAR in individuals with PTSD, and healthy controls with lifetime histories of trauma (trauma controls [TC]) and those without such histories (healthy controls [HC]). Untreated individuals with PTSD (N=25) with non-combat trauma histories, and TC (N=12) and HC (N=23) participated in a magnetic resonance (MR) imaging scan and a resting PET scan with the CB1 receptor antagonist radiotracer [11C]OMAR, which measures volume of distribution (VT) linearly related to CB1 receptor availability. Peripheral levels of anandamide, 2-arachidonoylglycerol (2-AG), oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and cortisol were also assessed. In the PTSD group, relative to the HC and TC groups, we found elevated brain-wide [11C]OMAR VT values (F(2,53)=7.96, p=.001; 19.5% and 14.5% higher, respectively) which were most pronounced in women (F(1,53)=5.52, p=.023). Anandamide concentrations were reduced in the PTSD relative to the TC (53.1% lower) and HC (58.2% lower) groups. Cortisol levels were lower in the PTSD and TC groups relative to the HC group. Three biomarkers examined collectively—OMAR VT, anandamide, and cortisol—correctly classified nearly 85% of PTSD cases. These results suggest that abnormal CB1 receptor-mediated anandamide signaling is implicated in the etiology of PTSD, and provide a promising neurobiological model to develop novel, evidence-based pharmacotherapies for this disorder

Integrative Clinical and Genomic Characterization of MTAP-deficient Metastatic Urothelial Cancer

Deficiency of MTAP (MTAPdef) mainly occurs because of homozygous loss of chromosome 9p21, which is the most common copy-number loss in metastatic urothelial cancer (mUC). We characterized the clinical and genomic features of MTAPdef mUC in 193 patients treated at MD Anderson Cancer Center (MDACC) and 298 patients from the phase 2 IMvigor210 trial, which investigated atezolizumab in cisplatin-ineligible and platinum-refractory disease. In the MDACC cohort, visceral metastases were significantly more common for MTAPdef (n = 48) than for MTAP-proficient (MTAPprof; n = 145) patients (75% vs 55.2%; p = 0.02). MTAPdef was associated with poor prognosis (median overall survival [mOS] 12.3 vs 20.2 mo; p = 0.007) with an adjusted hazard ratio of 1.93 (95% confidence interval 1.35–2.98). Similarly, IMvigor210 patients with MTAPlo (n = 29) had a higher incidence of visceral metastases than those with MTAPhi tumors (n = 269; 86.2% vs 72.5%; p = 0.021) and worse prognosis (mOS 8.0 vs 11.3 mo; p = 0.042). Hyperplasia-associated genes were more frequently mutated in MTAPdef tumors (FGFR3: 31% vs 8%; PI3KCA: 31% vs 19%), while alterations in dysplasia-associated genes were less common in MTAPdef tumors (TP53: 41% vs 67%; RB1: 0% vs 16%). Our findings support a distinct biology in MTAPdef mUC that is associated with early visceral disease and worse prognosis