Association of health behaviors in life's essential 8 and hypertension in adolescents: a cross-sectional study from the NHANES database.

BACKGROUND: Hypertension is a common condition during adolescence with increasing prevalence globally, alongside the epidemic of unhealthy lifestyles and obesity. Health behaviors have been shown to be associated with hypertension risk in adults. Life's essential 8 (LE8), as a comprehensive indicator to evaluate cardiovascular health (CVH), includes 4 health factors and 4 health behaviors. This study aims to evaluate the association between health behaviors defined in LE8 and hypertension among adolescents. METHODS: Data of this study were extracted from the National Health and Nutrition Examination Surveys (NHANES) 2007-2018. Health behaviors of LE8 including diet, physical activity and tobacco smoke exposure. The outcome was the odd of hypertension in adolescents. The weighted univariate and multivariate logistic regression was unitized to explore the relationship between CVH score and hypertension in adolescents. Subgroup analysis and sensitivity analysis were further conducted to explore the association across different populations. RESULTS: Totally 3,941 adolescents aged 12-17 years were included, with the mean aged of 14.48 ± 0.04 years. Of whom, 203 (5.15%) had hypertension. After adjusted all covariates, high CVH score was associated with the lower odds of hypertension (OR = 0.32, 95%CI: 0.17-0.61), especially in boys (OR = 0.23, 95%CI: 0.11-0.51) and adolescents with overweight/obesity (OR = 0.24, 95%CI: 0.10-0.56). Sensitivity analysis reported that the association between CVH score and the odds of hypertension was also robust after excluding self-reported hypertension and medication taking (OR = 0.37, 95%CI: 0.18-0.74). CONCLUSION: A high CVH score, indicating a greater adherence of health behaviors, was associated with a reduced odds of hypertension, especially among boys and overweight/obesity adolescents. Large-scale prospective cohort studies are needed to further explore the association between health behaviors defined in LE8 and hypertension among adolescents.

The role of AKR1B10 in osteogenic differentiation of mesenchymal stem cells and atrophic nonunion.

Atrophic nonunion is a chronic disease without effective medications. Here, high-throughput mRNA sequencing was used to explore the novel targets in atrophic nonunion. AKR1B10, a member of aldo-keto reductase family 1, is upregulated in atrophic nonunion tissues. There are currently no studies to reveal the role of AKR1B10 in atrophic nonunion. We used rat bone marrow-derived mesenchymal stem cells (BMSCs) to explore the effect of AKR1B10 on the osteogenic differentiation and autophagy. In vivo, we implanted collagen sponges loaded with LV-shAKR1B10-transduced BMSCs into rat fractured femurs to explore the role of AKR1B10 in fracture healing. The results showed that AKR1B10 reduced the activity of ALP, suppressed the expression of COL1A1, RUNX2 and OCN, and inhibited calcification deposition in osteogenically differentiated BMSCs. AKR1B10 reduced the expression of LC3II, decreased the number of autophagosomes, and promoted the expression of p62. In addition, the promoting effect of AKR1B10 knockdown on osteogenic differentiation of BMSCs was attenuated by 3-MA treatment. Implantation of collagen sponges found that knockdown of AKR1B10 promoted bone fracture healing. In conclusion, AKR1B10 inhibited the osteogenic differentiation and autophagy, and delayed the bone fracture healing. These results provide a new perspective on revealing the role of AKR1B10 in nonunion and may also provide a new therapeutic target for the treatment of nonunion.

A Novel Scale System Based on the Frailty Index and Laboratory Indicators for the Short-Term Prognosis of Patients with Acute Myocardial Infarction: A Retrospective Cohort Study.

Objective: Current scoring systems for short-term prognosis in patients with acute myocardial infarction (AMI) lack coverage of risk factors and have limitations in risk stratification. The aim of this study was to develop a novel assessment system based on laboratory indicators and frailty quantification to better infer short-term prognosis and risk indication in patients with AMI. Methods: A total of 365 patients with MI from January 2022 to June 2023 in Northern Jiangsu Province Hospital were included. The primary endpoint was all-cause mortality and major adverse cardiac events (MACE) during follow-up. A novel scoring model ranging from 0 to 12 was constructed, and the predictive ability of this scoring system was evaluated using the area under the receiver operating characteristic curve (AUC). Results: During follow-up, 68 patients experienced MACE. Five scoring indicators were selected through multivariate logistic regression analysis, resulting in a composite score with an AUC of 0.925, demonstrating good prognostic accuracy. Conclusion: The novel prognostic assessment system, which integrates age, Stress Hyperglycemia Ratio (SHR), Neutrophil to Lymphocyte Ratio (NLR), lactate, and frailty score, exhibits good predictive value for short-term MACE in patients with acute myocardial infarction and may enable more accurate risk classification for future use in MI patient risk management.

Selective translation of nuclear mitochondrial respiratory proteins reprograms succinate metabolism in AML development and chemoresistance.

Mitochondrial adaptations dynamically reprogram cellular bioenergetics and metabolism and confer key properties for human cancers. However, the selective regulation of these mitochondrial responses remains largely elusive. Here, inspired by a genetic screening in acute myeloid leukemia (AML), we identify RAS effector RREB1 as a translational regulator and uncover a unique translation control system for nuclear-encoded mitochondrial proteins in human cancers. RREB1 deletion reduces mitochondrial activities and succinate metabolism, thereby damaging leukemia stem cell (LSC) function and AML development. Replenishing complex II subunit SDHD rectifies these deficiencies. Notably, inhibition of complex II re-sensitizes AML cells to venetoclax treatment. Mechanistically, a short RREB1 variant binds to a conserved motif in the 3' UTRs and cooperates with elongation factor eEF1A1 to enhance protein translation of nuclear-encoded mitochondrial mRNAs. Overall, our findings reveal a unique translation control mechanism for mitochondrial adaptations in AML pathogenesis and provide a potential strategy for targeting this vulnerability of LSCs.

Effect of preoperative oral nutritional supplements on clinical outcomes in patients undergoing surgery for gastrointestinal cancer: A systematic review and meta-analysis.

BACKGROUND: The clinical benefit of preoperative oral nutritional supplements (ONS) in patients undergoing surgery for gastrointestinal cancer remains controversial. OBJECTIVE: To evaluate the effect of preoperative ONS on postoperative clinical outcomes in patients with gastrointestinal cancer. METHODS: We searched PubMed, EMBASE, Web of Science, Cochrane Library, Scopus, and the Chinese National Knowledge Infrastructure databases for randomized controlled trials evaluating preoperative ONS in patients undergoing surgery for gastrointestinal cancer from inception until April 2024. Two researchers independently assessed the quality of the included literature and performed statistical analyses using Review Manager 5.4 software. RESULTS: A total of 12 eligible studies with 1201 patients (600 ONS group and 601 control group) were included in this meta-analysis. Compared with a normal diet, preoperative ONS effectively reduced infectious complications (odds ratio = 0.63; 95% confidence interval [CI], 0.40-0.98; P = .04), white blood cell count (mean difference [MD] = -0.66; 95% CI, -1.04 to -0.28; P = .0007), C-reactive protein (MD = -0.26; 95% CI, -0.33 to -0.19; P < .00001), and markedly improved albumin levels (MD = 1.71; 95% CI, 0.97-2.46; P < .00001), prealbumin (MD = 24.80; 95% CI, 1.72-47.88; P = .04), immunoglobulin G (MD = 0.86; 95% CI, 0.44-1.28; P < .00001), CD4 T lymphocyte cells (MD = 3.06; 95% CI, 2.21-3.92; P < .00001), and CD4 T lymphocyte cells/CD8 T lymphocyte cells (MD = 0.33; 95% CI, 0.10-0.56; P = .004). However, there were no significant differences between the 2 groups in terms of noninfectious complications (odds ratio = 0.77; 95% CI, 0.39-1.53; P = .46), immunoglobulin A (MD = -0.21; 95% CI, -0.44 to 0.02; P = .08) or length of hospital stay (MD = -0.04; 95% CI, -0.71 to 0.64; P = .92). CONCLUSION: Preoperative ONS may effectively reduce postoperative infectious complications, improve postoperative nutritional status and immune function, and relieve the inflammatory response in gastrointestinal cancer patients. Therefore, we recommend that preoperative nutrition could be optimized with ONS in patients undergoing gastrointestinal cancer surgery.

Comparison of intravascular ultrasound-guided with optical coherence tomography-guided percutaneous coronary intervention for left main distal bifurcation lesions: Rationale and design of the ISOLEDS trial.

BACKGROUND: Percutaneous coronary intervention (PCI) can provide benefits for anatomically suitable left main coronary artery (LMCA) lesions. When compared to traditional coronary angiography (CAG) -guided PCI, the use of intravascular ultrasound (IVUS) guidance has shown significant long-term prognostic improvements in LMCA PCI. Optical coherence tomography (OCT) offers a higher axial resolution than IVUS. However, there is currently a lack of relevant randomized controlled trials investigating the use of OCT specifically for left main distal bifurcation lesions. METHODS: The ISOLEDS trial is an ongoing multicenter study that aims to compare IVUS-guided PCI with OCT-guided PCI for patients with true LMCA distal bifurcation lesions. This prospective, randomized, controlled, non-inferiority trial will enroll a total of 664 patients with visually-defined Medina 1,1,1 or 0,1,1 classification of left main distal bifurcation lesions. The patients will be randomly assigned in a 1:1 ratio to either IVUS-guided or OCT-guided PCI. The primary endpoint is to assess the occurrence of target lesion failure (TLF) within 12 months after the procedure. After undergoing PCI, patients are required to visit the hospital for a 12-month clinical follow-up. During this clinical assessment, CAG can be performed to evaluate the status of target lesions. DISCUSSION: The ISOLEDS trial represents the first attempt to compare two distinct intracoronary imaging techniques for guiding PCI in patients with true LMCA distal bifurcation lesions. By evaluating and comparing the outcomes of these two imaging techniques, the trial results will aid operators in selection of the most effective approach for guiding PCI in these patients.

Deep Learning Model for Pathological Grading and Prognostic Assessment of Lung Cancer Using CT Imaging: A Study on NLST and External Validation Cohorts.

RATIONALE AND OBJECTIVES: To develop and validate a deep learning model for automated pathological grading and prognostic assessment of lung cancer using CT imaging, thereby providing surgeons with a non-invasive tool to guide surgical planning. MATERIAL AND METHODS: This study utilized 572 cases from the National Lung Screening Trial cohort, dividing them randomly into training (461 cases) and internal validation (111 cases) sets in an 8:2 ratio. Additionally, 224 cases from four cohorts obtained from the Cancer Imaging Archive, all diagnosed with non-small cell lung cancer, were included for external validation. The deep learning model, built on the MobileNetV3 architecture, was assessed in both internal and external validation sets using metrics such as accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). The model's prognostic value was further analyzed using Cox proportional hazards models. RESULTS: The model achieved high accuracy, sensitivity, specificity, and AUC in the internal validation set (accuracy: 0.888, macro AUC: 0.968, macro sensitivity: 0.798, macro specificity: 0.956). External validation demonstrated comparable performance (accuracy: 0.807, macro AUC: 0.920, macro sensitivity: 0.799, macro specificity: 0.896). The model's predicted signatures correlated significantly with patient mortality and provided valuable insights for prognostic assessment (adjusted HR 2.016 [95% CI: 1.010, 4.022]). CONCLUSIONS: This study successfully developed and validated a deep learning model for the preoperative grading of lung cancer pathology. The model's accurate predictions could serve as a useful adjunct in treatment planning for lung cancer patients, enabling more effective and customized interventions to improve patient outcomes.

Comparable efficacy and safety of generic and branded imatinib for patients with chronic myeloid leukemia in China.

Background: Generics imatinib became an alternative treatment option for chronic myeloid leukemia (CML) patients in China. However, clinicians and patients alike harbor concerns regarding the long-term safety of generic imatinib. Objectives: Patients with chronic phase CML receiving frontline imatinib treatment. Design: A retrospective study was used to evaluate the blood concentration, effectiveness, and safety of generic in 170 CML patients. Methods: Imatinib plasma concentrations were detected by high-performance liquid chromatography-tandem mass spectrometry. Results: Among the 170 patients, 73 (42.9%) patients treated with branded imatinib as first-line therapy, while 22 (12.9%) switched to generic imatinib during treatment due to economic considerations. No significant differences in trough concentrations between branded and generic imatinib (1549.9 ± 648.8 ng/mL vs 1479.0 ± 507.0 ng/mL; p = 0.95). During the 2-year follow-up, there were no significant differences in molecular response rates (major molecular response (MMR): 33.3% vs 37.0%; deep molecular response: 56.9% vs 42.9%, p = 0.17) between the branded and generic imatinib. Both groups showed similar rates of switching to second-generation tyrosine kinase inhibitor (11.8% vs 15.1%, p = 0.56). Furthermore, there were no significant differences in event-free survival or failure-free survival between branded and generic imatinib. Twenty-two (12.9%) switched to generic imatinib during treatment, 68.2% maintained their level of response, 27.3% improved, and only one patient (4.5%) lost MMR. There were no significant differences in the incidence of various adverse events. Conclusion: Generic imatinib are equally effective and safe compared to branded molecules, both for newly diagnosed patients and those who switch from branded.

No difference in oncological outcomes and perioperative complications between patients with ESRD with unilateral and bilateral UTUC receiving radical nephroureterectomy.

Patients with end stage renal disease (ESRD) are at high risk of developing upper tract urothelial carcinoma (UTUC). Due to high recurrence rate of UTUC in contralateral kidney and ureter, and high risk of complications related to surgery and anesthesia, whether it's necessary to remove both kineys and ureters at one time remains in debate. We utilized Taiwanese UTUC Registry Database to valuate the difference of oncological outcomes and perioperative complications between patients with ESRD with unilateral and bilateral UTUC receiving surgical resection. Patients with ESRD and UTUC were divided into three groups, unilateral UTUC, previous history of unilateral UTUC with metachronous contralateral UTUC, and concurrent bilatetral UTUC. Oncological outcomes, perioperative complications, and length of hospital stays were investiaged. We found that there is no diffence of oncological outcomes including overall survival, cancer specific survival, disease free survival and bladder recurrence free survival between these three groups. Complication rate and length of hospital stay are similar. Adverse oncological features such as advanced tumor stage, lymph node involvement, lymphovascular invasion, and positive surgical margin would negatively affect oncological outcomes.

Deep learning large-scale drug discovery and repurposing.

Large-scale drug discovery and repurposing is challenging. Identifying the mechanism of action (MOA) is crucial, yet current approaches are costly and low-throughput. Here we present an approach for MOA identification by profiling changes in mitochondrial phenotypes. By temporally imaging mitochondrial morphology and membrane potential, we established a pipeline for monitoring time-resolved mitochondrial images, resulting in a dataset comprising 570,096 single-cell images of cells exposed to 1,068 United States Food and Drug Administration-approved drugs. A deep learning model named MitoReID, using a re-identification (ReID) framework and an Inflated 3D ResNet backbone, was developed. It achieved 76.32% Rank-1 and 65.92% mean average precision on the testing set and successfully identified the MOAs for six untrained drugs on the basis of mitochondrial phenotype. Furthermore, MitoReID identified cyclooxygenase-2 inhibition as the MOA of the natural compound epicatechin in tea, which was successfully validated in vitro. Our approach thus provides an automated and cost-effective alternative for target identification that could accelerate large-scale drug discovery and repurposing.

Targeting Macrophage Phenotypes and Metabolism as Novel Therapeutic Approaches in Atherosclerosis and Related Cardiovascular Diseases.

PURPOSE OF THE REVIEW: Macrophage accumulation and activation function as hallmarks of atherosclerosis and have complex and intricate dynamics throughout all components and stages of atherosclerotic plaques. In this review, we focus on the regulatory roles and underlying mechanisms of macrophage phenotypes and metabolism in atherosclerosis. We highlight the diverse range of macrophage phenotypes present in atherosclerosis and their potential roles in progression and regression of atherosclerotic plaque. Furthermore, we discuss the challenges and opportunities in developing therapeutic strategies for preventing and treating atherosclerotic cardiovascular disease. RECENT FINDINGS: Dysregulation of macrophage polarization between the proinflammatory M1 and anti-inflammatory M2 phenotypealters the immuno-inflammatory response during atherosclerosis progression, leading to plaque initiation, growth, and ultimately rupture. Altered metabolism of macrophage is a key feature for their function and the subsequent progression of atherosclerotic cardiovascular disease. The immunometabolism of macrophage has been implicated to macrophage activation and metabolic rewiring of macrophages within atherosclerotic lesions, thereby shifting altered macrophage immune-effector and tissue-reparative function. Targeting macrophage phenotypes and metabolism are potential therapeutic strategies in the prevention and treatment of atherosclerosis and atherosclerotic cardiovascular diseases. Understanding the precise function and metabolism of specific macrophage subsets and their contributions to the composition and growth of atherosclerotic plaques could reveal novel strategies to delay or halt development of atherosclerotic cardiovascular diseases and their associated pathophysiological consequences. Identifying biological stimuli capable of modulating macrophage phenotypes and metabolism may lead to the development of innovative therapeutic approaches for treating patients with atherosclerosis and coronary artery diseases.

LRG1 promotes atherosclerosis by inducing macrophage M1-like polarization.

Atherosclerosis is a chronic inflammatory disease of the arterial wall characterized by the accumulation of cholesterol-rich lipoproteins in macrophages. How macrophages commit to proinflammatory polarization under atherosclerosis conditions is not clear. Report here that the level of a circulating protein, leucine-rich alpha-2 glycoprotein 1 (LRG1), is elevated in the atherosclerotic tissue and serum samples from patients with coronary artery disease (CAD). LRG1 stimulated macrophages to proinflammatory M1-like polarization through the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) pathways. The LRG1 knockout mice showed significantly delayed atherogenesis progression and reduced levels of macrophage-related proinflammatory cytokines in a high-fat diet-induced Apoe-/- mouse atherosclerosis model. An anti-LRG1 neutralizing antibody also effectively blocked LRG1-induced macrophage M1-like polarization in vitro and conferred therapeutic benefits to animals with ApoE deficiency-induced atherosclerosis. LRG1 may therefore serve as an additional biomarker for CAD and targeting LRG1 could offer a potential therapeutic strategy for CAD patients by mitigating the proinflammatory response of macrophages.

A predictive model for therapy failure in patients with chronic myeloid leukemia receiving tyrosine kinase inhibitor therapy.

ABSTRACT: Although tyrosine kinase inhibitor (TKI) therapy has markedly improved the survival of people with chronic-phase chronic myeloid leukemia (CML), 20% to 30% of people still experienced therapy failure. Data from 1955 consecutive patients with chronic-phase CML diagnosed by the European LeukemiaNet recommendations from 1 center receiving initial imatinib or a second-generation (2G) TKI therapy were interrogated to develop a clinical prediction model for TKI-therapy failure. This model was subsequently validated in 3454 patients from 76 other centers. Using the predictive clinical covariates associated with TKI-therapy failure, we developed a model that stratified patients into low-, intermediate- and high-risk subgroups with significantly different cumulative incidences of therapy failure (P < .001). There was good discrimination and calibration in the external validation data set, and the performance was consistent with that of the training data set. Our model had the better prediction discrimination than the Sokal and European Treatment and Outcome Study long-term survival scores, with the greater time-dependent area under the receiver-operator characteristic curve values and a better ability to redefine the risk of therapy failure. Our model could help physicians estimate the likelihood of initial imatinib or 2G TKI-therapy failure in people with chronic-phase CML.

Chromosome-scale genome assemblies of sexually dimorphic male and female Acrossocheilus fasciatus.

Acrossocheilus fasciatus is a stream-dwelling fish species of the Barbinae subfamily. It is valued for its colorfully striped appearance and delicious meat. This species is also characterized by apparent sexual dimorphism and toxic ovum. Biology and aquaculture researches of A. fasciatus are hindered by the lack of a high-quality reference genome. Here, we report chromosome-level genome assemblies of the male and female A. fasciatus. The HiFi-only genome assemblies for both female and male individuals were 899.13 Mb (N50 length of 32.58 Mb) and 885.68 Mb (N50 length of 33.06 Mb), respectively. Notably, a substantial proportion of the assembled sequences, accounting for 96.15% and 98.35% for female and male genomes, respectively, were successfully anchored onto 25 chromosomes utilizing Hi-C data. We annotated the female assembly as a reference genome and identified a total of 400.62 Mb (44.56%) repetitive sequences, 27,392 protein-coding genes, and 35,869 ncRNAs. The high-quality male and female reference genomes will provide genomic resources for developing sex-specific molecular markers, inform single-sex breeding, and elucidate genetic mechanisms of sexual dimorphism.

A bifunctional primitive strategy induces enhancements of large second harmonic generation and wide UV transmittance in rare-earth borates containing [B5O10] groups.

Strong second-harmonic generation (SHG) and a short ultraviolet (UV) cutoff edge are two crucial yet often conflicting parameters that must be finely tuned in the exploration of nonlinear optical (NLO) materials. In this study, two new rare earth borate NLO crystals, K7BaSc2B15O30 (KBSBO) and Rb21Sr3.8Sc5.2B45O90 (RSSBO), were rationally designed through a bifunctional primitive strategy to achieve an optimized balance between favorable SHG efficiency and UV transparency. As anticipated, both KBSBO and RSSBO exhibit a wide UV transparency window below 190 nm. Notably, these tailored crystals display strong SHG responses, with RSSBO achieving a remarkable enhancement in SHG efficiency (2 × KDP), surpassing that of most deep-UV rare earth borates containing [B5O10] groups known to date. Theoretical calculations and structural analyses reveal that the impressive SHG activities primarily stem from the [B5O10] groups and [ScO6] polyhedra. These findings suggest promising potential for KBSBO and RSSBO crystals as beryllium-free deep UV NLO materials.

Aerobic Se(IV) reducing bacteria and their reducing characteristics in estuarine sediment.

Microorganisms play a critical role in the biogeochemical cycling of selenium in natural ecosystems, particularly in reducing selenite (Se(IV)) to element selenium (Se(0)) which reduces its mobility and bioavailability. However, Se(IV)-reducing bacteria and their reducing characteristics in estuarine sediments remain inadequately understood. In this study, the reduction of Se(IV) was confirmed to be microbially driven through the cultivation of a mixture of estuarine sediment and Se(IV) under aerobic conditions. Community analysis indicates that Bacillus was primarily involved in the reduction of Se(IV). A strain with high salt tolerance (7.5 % NaCl) and Se(IV) resistance (up to 200 mM), Bacillus cereus SD1, was isolated from an estuarine sediment. The reduction of Se(IV) occurred concomitantly with the onset of microbial growth, and reduction capacity increased approximately 5-fold by adjusting the pH. In addition, Se(IV) reduction in Bacillus cereus SD1 was significantly inhibited by sulfite, and the key enzyme activity tests revealed the possible presence of a sulfite reductase-mediated Se(IV) reduction pathway. These research findings provide new insights into the bioreducing characteristics and the biogeochemical cycling of selenium in estuarine environments.

Safety and efficacy of flumatinib as later-line therapy in patients with chronic myeloid leukemia.

To evaluate the efficacy and safety of flumatinib in the later-line treatment of Chinese patients with Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia (CP-CML previously treated with tyrosine kinase inhibitors (TKIs). Patients with CML-CP were evaluated for the probabilities of responses including complete hematologic response (CHR), cytogenetic response, and molecular response (MR) and adverse events (AEs) after the later-line flumatinib therapy. Of 336 enrolled patients with median age 50 years, median duration of treatment with flumatinib was 11.04 (2-25.23) months. Patients who achieved clinical responses at baseline showed maintenance of CHR, complete cytogenetic response (CCyR)/2-log molecular response (MR2), major molecular response (MMR), and 4-log molecular response or deep molecular response (MR4/DMR) in 100%, 98.9%, 98.6%, and 92.9% patients, respectively. CHR, CCyR/MR2, MMR, and MR4/DMR responses were achieved in 86.4%, 52.7%, 49.6%, and 23.5% patients respectively, which showed the lack of respective clinical responses at baseline. The patients without response at baseline, treated with flumatinib as 2L TKI, having no resistance to prior TKI or only resistance to imatinib, with response to last TKI, and with BCR::ABL ≤10% had higher CCyR/MR2, MMR, or MR4/DMR. The AEs observed during the later-line flumatinib treatment were tolerable and consistent with those reported with the first-line therapy. Flumatinib was effective and safe in patients who are resistant or intolerant to other TKIs. In particular, 2L flumatinib treatment induced high response rates and was more beneficial to patients without previous 2G TKI resistance, thus serving as a probable treatment option for these patients.