Extracellular vesicle-mediated regulation of imatinib resistance in chronic myeloid leukemia via the miR-629-5p/SENP2/PI3K/AKT/mTOR axis.

BACKGROUND: Imatinib (IM) is the primary treatment for patients with chronic-phase CML (CML-CP). However, an increasing number of CML-CP patients have developed resistance to IM. Our study aims to explore the expression of miR-629-5p in extracellular vesicles (EVs) from both IM-sensitive (K562) and resistant (K562-Re) CML cell lines and to investigate the impact of regulating miR-629-5p expression on the biological characteristics of K562 and K562-Re cells. METHODS: Assess miR-629-5p expression levels in IM-sensitive and resistant CML cell lines. Separate EVs and verify it. EVs from K562-Re cells were co-cultured with K562 cells to detect the expression level of miR-629-5p. Target genes of miR-629-5p were determined and validated through luciferase experiments. Examined by manipulating miR-629-5p expression in cells using transfection techniques. The expression level of phosphorylated proteins in the PI3K/AKT/mTOR signaling pathway after IM was detected in CML cell lines. In K562-Re cells, the expression level of phosphorylated protein in the PI3K/AKT/mTOR signaling pathway was detected after single transfection of miR-629-5p inhibitor and cotransfection of miR-629-5p inhibitor and siSENP2. RESULTS: Increasing concentrations of EVs from K562-Re cells elevated miR-629-5p expression levels. The expression levels of miR-629-5p in CML cells varied with IM concentration and influenced the biological characteristics of cells. SENP2 was identified as a target gene of miR-629-5p. Furthermore, miR-629-5p was found to modulate the SENP2/PI3K/AKT/mTOR pathway, impacting IM resistance in CML cells. CONCLUSION: EVs from IM-resistant CML cells alter the expression of miR-629-5p in sensitive cells, activating the SENP2/PI3K/AKT/mTOR pathway and leading to IM resistance.

A retrospective study on the efficacy of the ERAS protocol in patients who underwent laparoscopic left and right colectomy surgeries.

Objective: Retrospective analysis and comparison of the effects of Enhanced Recovery After Surgery (ERAS) protocol for patients having left and right colectomy surgeries. Method: Out of the patients admitted to Chengdu Shang Jin Nan Fu Hospital and West China Hospital from December 2019 to December 2022, a total of 498 who met the inclusion criteria were selected, 255 with right colectomy(RC) and 243 with left colectomy (LC). Under the conditions of strict compliance with ERAS protocol, the relevant physical indexes of RC and LC, including postoperative rehabilitation (especially median post-operative stay) and complications (especially prolonged postoperative ileus, PPOI), were statistically analyzed and compared. Results: In terms of intraoperative variables, fluid doses were higher in the LC group than in the RC group (P < 0.05), and there was no significant difference between them in terms of operative time, blood loss, need for open surgery, peritoneal contamination, epidural catheter placement, or opioid use (P > 0.05). Compared with the RC group, the LC group had a higher intake of oral liquid at the second postoperative day (POD), and faster first flatulence (P < 0.05). 30 (11.76%) RC patients required nasogastric tube insertion, while only 3 (1.23%) patients in the LC group required the same (P < 0.05). Prolonged postoperative ileus (PPOI) occurred in 48 (18.82%) and 29 (11.93%) patients in the RC and LC groups, respectively (P < 0.05). No significant differences in terms of postoperative complications or length of hospital stay (LoS). stay were observed. Conclusion: As the location of colon cancer changes, the effectiveness of ERAS also varies. More personalized and precise ERAS protocols can reduce the incidence of postoperative complications and promote rapid recovery after surgery.

Improving denitrification estimation by joint inclusion of suspended particles and chlorophyll a in aquaculture ponds.

The denitrification process in aquaculture systems plays a crucial role in nitrogen (N) cycle and N budget estimation. Reliable models are needed to rapidly quantify denitrification rates and assess nitrogen losses. This study conducted a comparative analysis of denitrification rates in fish, crabs, and natural ponds in the Taihu region from March to November 2021, covering a complete aquaculture cycle. The results revealed that aquaculture ponds exhibited higher denitrification rates compared to natural ponds. Key variables influencing denitrification rates were Nitrate nitrogen (NO3--N), Suspended particles (SPS), and chlorophyll a (Chla). There was a significant positive correlation between SPS concentration and denitrification rates. However, we observed that the denitrification rate initially rose with increasing Chla concentration, followed by a subsequent decline. To develop parsimonious models for denitrification rates in aquaculture ponds, we constructed five different statistical models to predict denitrification rates, among which the improved quadratic polynomial regression model (SQPR) that incorporated the three key parameters accounted for 80.7% of the variability in denitrification rates. Additionally, a remote sensing model (RSM) utilizing SPS and Chla explained 43.8% of the variability. The RSM model is particularly valuable for rapid estimation in large regions where remote sensing data are the only available source. This study enhances the understanding of denitrification processes in aquaculture systems, introduces a new model for estimating denitrification in aquaculture ponds, and offers valuable insights for environmental management.

Association of point-of-care testing for sST2 with clinical outcomes in patients hospitalized with heart failure.

AIMS: This study aimed to investigate the association of soluble suppression of tumorigenicity-2 (sST2) measured by point-of-care testing assay with clinical outcomes in patients hospitalized with heart failure after adjusting for other predictors including N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT). METHODS: A total of 1726 consecutive patients hospitalized with heart failure from July 2015 to December 2021 were enrolled. Baseline serum sST2 concentrations were measured by immunofluorescence assay. Primary endpoint event was the composite of all-cause death, heart transplantation, or left ventricular assist device. RESULTS: During the median follow-up duration of 682 days, 434 patients (25.1%) suffered from primary endpoint events. Baseline sST2 remained an independent predictor of the primary endpoint event in patients hospitalized with heart failure after adjusting for other predictors including NT-proBNP and hs-cTnT [per log (unit) increase, adjusted hazard ratio (HR) (95% confidence interval) (CI): 1.20 (1.09, 1.32), P < 0.001]. And baseline sST2 had a better prognostic value for patients with chronic decompensated heart failure [per log (unit) increase, adjusted HR (95% CI): 1.19 (1.07, 1.31)] than for those with acute new onset heart failure [per log (unit) increase, adjusted HR (95% CI): 1.28 (0.94, 1.75), P value for interaction <0.001], as well as a better prognostic value for patients with New York Heart Association (NYHA) functional class I-II [per log (unit) increase, adjusted HR (95% CI): 1.67 (1.11, 2.52)] than for those with NYHA functional class III-IV [per log (unit) increase, adjusted HR (95% CI): 1.18 (1.07, 1.31), P value for interaction <0.001]. Baseline sST2 was also a good predictor of the primary endpoint event in patients hospitalized with heart failure at 1 month, 3 months, 1 year and 2 years (area under the curve: 0.789, 0.775, 0.736 and 0.733, respectively), and the best cut-off values were 27.2 ng/ml, 27.1 ng/ml, 27.1 ng/ml and 25.1 ng/ml, respectively. Furthermore, baseline sST2 could provide additional prognostic value when added to baseline NT-proBNP and hs-cTnT (all P values <0.05). According to the category of elevated biomarkers (including NT-proBNP, hs-cTnT, and sST2), patients with three elevated biomarkers had a higher risk of the primary endpoint event compared with those with one or two elevated biomarkers (all P values <0.05). CONCLUSIONS: Baseline sST2 remained an independent predictor of adverse events after adjusting for other predictors including NT-proBNP and hs-cTnT, particularly in patients with chronic decompensated heart failure and NYHA functional class I-II. And in the basis of baseline NT-proBNP and hs-cTnT, adding baseline sST2 could provide additional prognostic value for patients hospitalized with heart failure.

miR397 regulates cadmium stress response by coordinating lignin polymerization in the root exodermis in Kandelia obovata.

Secondary lignification of the root exodermis of Kandelia obovata is crucial for its response to adversity such as high salinity and anaerobic environment, and this lignification is also effective in blocking cadmium transport to the roots. However, how the differences in lignification of root exodermis at different developmental stages respond to Cd stress and its regulatory mechanisms have not been revealed. In this study, after analyzing the root structure and cell wall thickness using a Phenom scanning electron microscope as well as measuring cadmium content in the root cell wall, we found that the exodermis of young and mature roots of K. obovata responded to Cd stress through the polymerization of different lignin monomers, forming two different mechanisms: chelation and blocking. Through small RNA sequencing, RLM-5'-RACE and dual luciferase transient expression system, we found that miR397 targets and regulates KoLAC4/17/7 expression. The expression of KoLAC4/17 promoted the accumulation of guaiacyl lignin during lignification and enhanced the binding of cadmium to the cell wall. Meanwhile, KoLAC7 expression promotes the accumulation of syringyl lignin during lignification, which enhances the obstruction of cadmium and improves the tolerance to cadmium. These findings enhance our understanding of the molecular mechanisms underlying the differential lignification of the root exodermis of K. obovata in response to cadmium stress, and provide scientific guidance for the conservation of mangrove forests under heavy metal pollution.

Inhibitors of Cyclophilin A: Current and Anticipated Pharmaceutical Agents for Inflammatory Diseases and Cancers.

Cyclophilin A, a widely prevalent cellular protein, exhibits peptidyl-prolyl cis-trans isomerase activity. This protein is predominantly located in the cytosol; additionally, it can be secreted by the cells in response to inflammatory stimuli. Cyclophilin A has been identified to be a key player in many of the biological events and is therefore involved in several diseases, including vascular and inflammatory diseases, immune disorders, aging, and cancers. It represents an attractive target for therapeutic intervention with small molecule inhibitors such as cyclosporin A. Recently, a number of novel inhibitors of cyclophilin A have emerged. However, it remains elusive whether and how many cyclophilin A inhibitors function in the inflammatory diseases and cancers. In this review, we discuss current available data about cyclophilin A inhibitors, including cyclosporin A and its derivatives, quinoxaline derivatives, and peptide analogues, and outline the most recent advances in clinical trials of these agents. Inhibitors of cyclophilin A are poised to enhance our comprehension of the molecular mechanisms that underpin inflammatory diseases and cancers associated with cyclophilin A. This advancement will aid in the development of innovative pharmaceutical treatments in the future.

Directed Evolution of Escherichia coli Nissle 1917 to Utilize Allulose as Sole Carbon Source.

Sugar substitutes are popular due to their akin taste and low calories. However, excessive use of aspartame and erythritol can have varying effects. While D-allulose is presently deemed a secure alternative to sugar, its excessive consumption is not devoid of cellular stress implications. In this study, the evolution of Escherichia coli Nissle 1917 (EcN) is directed to utilize allulose as sole carbon source through a combination of adaptive laboratory evolution (ALE) and fluorescence-activated droplet sorting (FADS) techniques. Employing whole genome sequencing (WGS) and clustered regularly interspaced short palindromic repeats interference (CRISPRi) in conjunction with compensatory expression displayed those genetic mutations in sugar and amino acid metabolic pathways, including glnP, glpF, gmpA, nagE, pgmB, ybaN, etc., increased allulose assimilation. Enzyme-substrate dynamics simulations and deep learning predict enhanced substrate specificity and catalytic efficiency in nagE A247E and pgmB G12R mutants. The findings evince that these mutations hold considerable promise in enhancing allulose uptake and facilitating its conversion into glycolysis, thus signifying the emergence of a novel metabolic pathway for allulose utilization. These revelations bear immense potential for the sustainable utilization of D-allulose in promoting health and well-being.

Surface and underwater human pose recognition based on temporal 3D point cloud deep learning.

Airborne surface and underwater human pose recognition are crucial for various safety and surveillance applications, including the detection of individuals in distress or drowning situations. However, airborne optical cameras struggle to achieve simultaneous imaging of the surface and underwater because of limitations imposed by visible-light wavelengths. To address this problem, this study proposes the use of light detection and ranging (LiDAR) to simultaneously detect humans on the surface and underwater, whereby human poses are recognized using a neural network designed for irregular data. First, a temporal point-cloud dataset was constructed for surface and underwater human pose recognition to enhance the recognition of comparable movements. Subsequently, radius outlier removal (ROR) and statistical outlier removal (SOR) were employed to alleviate the impact of noise and outliers in the constructed dataset. Finally, different combinations of secondary sampling methods and sample sizes were tested to improve recognition accuracy using PointNet++. The experimental results show that the highest recognition accuracy reached 97.5012%, demonstrating the effectiveness of the proposed human pose detection and recognition method.

Refractory Anti- N -Methyl- d -Aspartate Receptor Autoimmune Encephalitis Induced by Ovarian Teratoma: A Case Report.

OBJECTIVE: Teratoma is a type of germ cell tumor that derived from early embryonic stem cells and germ cell lines, which can lead to a rare complication known as paraneoplastic encephalitis syndrome. Delayed removal of teratoma allows for continuing antigen presentation, inducing affinity maturation of the antibody and the generation of long-lived plasma cells that infiltrate both bone marrow and brain, which makes the patient nonresponsive to later removal of teratoma and refractory to immunotherapy. We present this rare case to remind clinicians to be vigilant for the recognition and removal of teratoma during the treatment of autoimmune encephalitis. METHODS: We retrospectively reviewed the clinical record of this 12-year 5-month-old female patient diagnosed with anti- N -methyl- d -aspartate receptor (anti-NMDAR) autoimmune encephalitis; her ovarian teratoma was unidentified on admission. She did not respond to immunosuppressive therapy until the mature ovarian teratoma identified 45 days after admission and removed the following day, nearly 2 months after symptom onset. This patient experienced nearly complete resolution of symptoms within the subsequent 2 weeks. In addition, we conducted a literature review of the clinical presentations and treatment of anti-NMDAR autoimmune encephalitis associated with ovarian teratoma in the pediatric population. RESULTS: Our findings suggest that clinicians should be vigilant for the recognition and removal of teratoma during the treatment of autoimmune encephalitis. CONCLUSION: Female pediatric patients with suspected anti-NMDAR encephalitis should be screened for ovarian tumors immediately and treated in a multidisciplinary setting including neurology and obstetrics and gynecology.

Renal function modifies the association between hemoconcentration and outcomes in hospitalized heart failure patients.

Evidence-based management of decongestion is lacking in hospitalized heart failure (HHF) patients, especially in patients with impaired renal function. Hemoconcentration is an objective measure of decongestion that portends a favorable prognosis and guides management in HHF patients with preserved renal function. We aim to investigate whether it remains a prognosticator in patients with renal impairment, and to refine the identification of subpopulations who will benefit from hemoconcentration-guided therapy. HHF patients admitted to Heart Failure Center of Fuwai Hospital were consecutively included from December 2006 to June 2018. Patient characteristics were depicted. Relationships between in-hospital hemoconcentration, worsening renal function (WRF), and one-year all-cause mortality were investigated in the total population and compared between renal function groups using survival analysis and cubic splines, with a special focus on renal function-based interactions. The association was further validated in sensitivity analyses. Clinically relevant cut-offs and subpopulations were identified by subpopulation treatment effect pattern plots (STEPP) and subgroup analysis. 3661 participants (30.4% with impaired renal function) were included. Hemoconcentration, reflected by an in-hospital increase in hemoglobin, hematocrit, or a relative reduction in estimated plasma volume from baseline to discharge, was predictive of decreased one-year mortality in the total cohort despite its correlation with higher WRF incidence. The prognostic value of hemoconcentration differed in patients with impaired and preserved renal function. Hemoconcentration was related to a favorable prognosis in patients with preserved renal function (HR, 0.69; 95% CI, 0.53-0.90; P = 0.007), especially in young male patients with New York Heart Association functional class III-IV, reduced ejection fraction, and baseline eGFR > 75 mL/min/1.73m2. Contrarily, impaired renal function patients experienced a higher incidence of WRF, and hemoconcentration was no longer related to outcome (HR, 0.90; 95% CI, 0.64-1.26; P = 0.545), with findings consistent in all clinically relevant subgroups. In HHF patients, the prognostic value of hemoconcentration differs by renal function, and the clinical utility of hemoconcentration is contingent on preserved renal function.

A Strategy for Rescuing a Child From Clonazepam Poisoning: A Case Study.

BACKGROUND: This report describes the successful rescue of a 12-year-old girl who ingested large quantities of clonazepam tablets. METHODS: The patient was promptly treated with flumazenil and hemoperfusion to alleviate the symptoms of central depression. Therapeutic drug monitoring was used to evaluate detoxification efficacy. The authors analyzed the rescue protocol for clonazepam poisoning based on the pathophysiology, clinical manifestations, and pharmacokinetics of clonazepam overdose. RESULTS: The patient responded well to the treatment and was discharged from the hospital without adverse events. CONCLUSIONS: This case study demonstrated the effectiveness and safety of combining flumazenil with hemoperfusion as a treatment for clonazepam poisoning. This study aimed to provide insights into more effective methods for treating clonazepam overdose and contribute to the ongoing issue of managing this condition.

Cumulative remnant cholesterol as a causal risk factor for ischemic heart disease: A prospective cohort study.

BACKGROUND: While previous studies have established a significant correlation between baseline remnant cholesterol (RC) and ischemic heart disease (IHD), the enduring impact of RC on incident IHD remains to be elucidated. This study aimed to investigate the association between cumulative remnant cholesterol(cumRC) and IHD susceptibility. METHODS: Participating from the Kailuan Study (2006-2010) were enrolled, excluding those with prior myocardial infarction, coronary artery revascularization and cancer across three consecutive examinations. The cumRC derived by multiplying the average RC with the interval between the two consecutive assessments. Participants were segmented into quartiles based on cumRC levels: Q1 (cumRC < 2.69 mmol/l); Q2 (2.69 ≤ cumRC < 4.04 mmol/l); Q3(4.04 ≤ cumRC < 5.65 mmol/l) and Q4 (cumRC ≥ 5.65 mmol/l). The correlation between cumRC and IHD risk was ascertained by using multivariable Cox proportional hazard models. RESULT: The analysis encompassed 42,639 participants. Over an average tracking period of 9.97 years, 1,205 instances of IHD were identified. IHD susceptibility augmented with rising cumRC quartiles. After adjusting for potential confounders, the hazard ratios for IHD events were 1.06 (0.88-1.29) for Q2, 1.30 (1.08-1.56) for Q3 and 1.69 (1.42-2.01) for Q4, relative to Q1. Elevated cumRC was significantly associated with a heightened IHD risk, a trend consistent in both subgroup and sensitivity analyses. CONCLUSION: Elevated cumRC significantly correlates with a higher risk of IHD, suggesting that consistent monitoring and regulation of RC might be instrumental in IHD prevention.

Weight fluctuations preceding and succeeding heart failure diagnosis: Implications for all-cause mortality.

OBJECTIVE: This study aims to explore the ramifications of weight fluctuations preceding and succeeding the identification of heart failure (HF) on all-cause mortality. METHODS: The research cohort comprised individuals engaged in the Kailuan Group's health assessments from 2006 to 2018, who were subsequently diagnosed with HF. The moment of HF recognition marked the commencement of the monitoring period, culminating either at the instance of comprehensive mortality or at the conclusion of the monitoring phase (December 31, 2021). RESULTS: Throughout an average monitoring span of 5.8±3.5 years, from the 3115 qualified participants, 957 instances (30.7%) encountered comprehensive mortality. The COX proportional hazards regression model's outcomes revealed that, post the adjustment for potential confounders, in comparison to the Q3 category, the Q1 category had the highest hazard ratios (95% confidence intervals) of 1.71 (1.43-2.05). CONCLUSION: Weight reduction before and post the HF diagnosis stands as an autonomous risk determinant for comprehensive mortality.

A Case of Reversible Cardiomyopathy Due to Pre-Excitation.

BACKGROUND Pre-excitation cardiomyopathy is a specific type of cardiac disease related to asymptomatic pre-excitation. It is rarely reported and is prone to misdiagnosis; therefore, the actual incidence of pre-excitation cardiomyopathy may be underestimated. The purpose of this case report is to present a case of pre-excitation cardiomyopathy caused by an accessory pathway. CASE REPORT A 25-year-old woman was admitted to the hospital with concerns of recurrent chest tightness and decreased exercise tolerance for 3 months. Pre-excitation was found by electrocardiogram. Contraction of the left ventricular wall reduced diffusely, and the overall left ventricle moved asynchronously. The regional septum basal segment swung to the right ventricle like an aneurysm in systolic period. No significant myocardial fibrosis was found. Pathological examination of endomyocardial biopsy demonstrated nonspecific changes of mild interstitial edema. Pre-excitation cardiomyopathy was eventually diagnosed. A right anteroseptal para-hisian manifest accessory pathway was located in an electrophysiological study, and radiofrequency catheter ablation was subsequently performed to block the advanced conduction. During the follow-up at 6 months after ablation, left ventricular dyssynchrony and systolic dysfunction were improved and symptoms were significantly relieved. CONCLUSIONS Pre-excitation cardiomyopathy is characterized by asynchronous left ventricular motion, impaired cardiac function, and manifestations of heart failure. Asynchronous electromechanical contraction coupling plays an essential role in the pathogenesis. Blocking the accessory pathway could help to correct the dyssynchrony, reverse remodeling, improve left ventricular function, and alleviate symptoms. Patients can have a good prognosis through accurate diagnosis and appropriate treatment.

sST2 and Big ET-1 as Alternatives of Multi-Biomarkers Strategies for Prognosis Evaluation in Patients Hospitalized with Heart Failure.

Objective: To identify biomarkers with independent prognostic value and investigate the prognostic value of multiple biomarkers in combination in patients hospitalized with heart failure. Methods: A total of 884 consecutive patients hospitalized with heart failure from 2015 to 2017 were enrolled. Twelve biomarkers were measured on admission, and the relationships between biomarkers and outcomes were assessed. Results: During the median follow-up of 913 days, 291 patients (32.9%) suffered from primary endpoint events. Soluble suppression of tumorigenicity-2 (sST2) (per log [unit] increase, adjusted HR [95% CI]: 1.39 [1.13,1.72], P = 0.002) and big endothelin-1 (big ET-1) (per log [unit] increase, adjusted HR [95% CI]: 1.56 [1.23,1.97], P < 0.001) remained independent predictors of primary endpoint event after adjusting for other predictors including N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT). Both sST2 (C-statistic: 0.810 vs 0.801, P = 0.005, and 0.832 vs 0.826, P = 0.024, respectively) and big ET-1 (C-statistic: 0.829 vs 0.801, P = 0.001, and 0.843 vs 0.826, P < 0.001, respectively) significantly improved the predictive value for primary endpoint event at 1 year and 3 years. However, only big ET-1 (C-statistic: 0.852 vs 0.846, P = 0.014) significantly improved the predictive value at 3 months when added to clinical predictors and known biomarkers. According to the number of elevated biomarkers (including NT-proBNP, hs-cTnT, sST2, and big ET-1), patients with three or more elevated biomarkers had a higher risk of primary endpoint event compared to those with two elevated biomarkers (P = 0.001), as well as in patients with two elevated biomarkers compared to those with one elevated biomarker (P = 0.004). However, the risk of primary endpoint event was comparable between patients with one elevated biomarker and those with no elevated biomarker (P = 0.582). Conclusion: Multiple biomarkers in combination could provide a better prognostic value than a single biomarker. sST2 and big ET-1 could act as alternatives of multi-biomarkers strategies for prognosis evaluation beyond NT-proBNP and hs-cTnT in patients hospitalized with heart failure.

Clinical characteristics and outcomes of patients hospitalized with heart failure with preserved ejection fraction and low NT-proBNP levels.

The aim of this study was to investigate the clinical characteristics and prognosis of patients hospitalized with heart failure with preserved ejection fraction (HFpEF) and low N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Seven hundred ninety consecutive patients hospitalized with HFpEF from 2006 to 2017 were enrolled. Clinical characteristics and outcomes were compared between low NT-proBNP group (<300 ng/L) and elevated NT-proBNP group (≥300 ng/L). 108 HFpEF patients (13.7%) presented with low NT-proBNP levels. Age, body mass index, atrial fibrillation, New York Heart Association functional class, and albumin were independent predictors of low NT-proBNP levels in HFpEF patients. During the median follow-up duration of 1103 days, 11 patients (10.2%) in low NT-proBNP group suffered from primary endpoint event. Elevated NT-proBNP group had a higher risk of all-cause death or heart transplantation than low NT-proBNP group (adjusted HR [95%CI]: 2.36 [1.24,4.49], P = .009). Stratified analyses showed that the association between NT-proBNP (elevated NT-proBNP group vs low NT-proBNP group) and risk of all-cause death or heart transplantation was stronger in non-atrial fibrillation patients than in atrial fibrillation patients (P value for interaction = .025). Furthermore, the associations between NT-proBNP and risk of all-cause death or heart transplantation were stronger in younger and male patients than in older and female patients. However, both subgroups only reached borderline significant (P values for interaction = .062 and .084, respectively). Our findings suggest that low NT-proBNP levels were common in patients hospitalized with HFpEF. Patients with HFpEF and low NT-proBNP levels had a better prognosis than those with elevated NT-proBNP levels, particularly in younger, male, and non-atrial fibrillation patients.

HNEAP Regulates Necroptosis of Cardiomyocytes by Suppressing the m5 C Methylation of Atf7 mRNA.

PIWI-interacting RNAs (piRNAs) are highly expressed in various cardiovascular diseases. However, their role in cardiomyocyte death caused by ischemia/reperfusion (I/R) injury, especially necroptosis, remains elusive. In this study, a heart necroptosis-associated piRNA (HNEAP) is found that regulates cardiomyocyte necroptosis by targeting DNA methyltransferase 1 (DNMT1)-mediated 5-methylcytosine (m5 C) methylation of the activating transcription factor 7 (Atf7) mRNA transcript. HNEAP expression level is significantly elevated in hypoxia/reoxygenation (H/R)-exposed cardiomyocytes and I/R-injured mouse hearts. Loss of HNEAP inhibited cardiomyocyte necroptosis and ameliorated cardiac function in mice. Mechanistically, HNEAP directly interacts with DNMT1 and attenuates m5 C methylation of the Atf7 mRNA transcript, which increases Atf7 expression level. ATF7 can further downregulate the transcription of Chmp2a, an inhibitor of necroptosis, resulting in the reduction of Chmp2a level and the progression of cardiomyocyte necroptosis. The findings reveal that piRNA-mediated m5 C methylation is involved in the regulation of cardiomyocyte necroptosis. Thus, the HNEAP-DNMT1-ATF7-CHMP2A axis may be a potential target for attenuating cardiac injury caused by necroptosis in ischemic heart disease.

Estimated plasma volume status adds prognostic value to hemodynamic parameters in advanced heart failure.

BACKGROUND: Estimated plasma volume status (ePVS) is a marker of intravascular congestion and has prognostic value in patients with heart failure (HF). The elevation of intracardiac filling pressures is defined as hemodynamic congestion and is also associated with poor prognosis. However, the relationship between intravascular congestion and hemodynamic congestion remains unclear. This study sought to explore the correlation between ePVS and hemodynamic parameters and determine the association between ePVS and clinical outcomes in patients with advanced HF. METHODS: Patients with advanced HF underwent right heart catheterization (RHC) for hemodynamic profiles. The sum of right atrial pressure (RAP) and pulmonary arterial wedge pressure (PAWP) > 30 mmHg was considered to present with hemodynamic congestion. Blood tests were conducted within 24 h of RHC. We calculated ePVS using the Strauss-derived Duarte formula. The primary outcome was all-cause mortality. RESULTS: A total of 195 patients were divided into two groups based on the cut-off value of ePVS (4.08 dL/g) calculated from receiver operating characteristic analysis. Patients with ePVS > 4.08 dL/g were more likely to present with wet rales (21.2% vs. 9.9%, P = 0.032) and had a higher risk of death (HR 4.748, 95% CI 2.385-9.453), regardless of whether RAP + PAWP was normal or elevated (all P < 0.05). Hemodynamic parameters and ePVS were not correlated (all P > 0.05). High ePVS significantly improved the predictive value beyond the clinical plus hemodynamic prognostic model (area under the curve of 0.844, Delong test, P = 0.024). CONCLUSION: ePVS could additionally add prognostic value to hemodynamic parameters in advanced heart failure, although not correlated with hemodynamic parameters.