Numerical Study on Chemical Kinetic Characteristics of Counterflow Diffusion Flame Extinction of Methane/Ammonia/Air Flame under High Pressure or Air Preheating Temperature.

Green ammonia has become an increasingly popular fuel in recent years because of its combustion process without carbon oxide release. Adding ammonia to methane fuel for co-combustion has become one of the important research topics in the current combustion field. In the present study, the CH4/NH3/Air counterflow diffusion flame was taken as the research object, and Chemkin-2019 R3 software was used to explore and analyze the flame extinction limit and chemical kinetics characteristics under different ammonia mixing ratios, initial pressures, and air preheating temperatures. It was obtained that the flame extinction stretch rate was decreased by increasing the NH3 mole fraction in the CH4/NH3 mixed fuel. The increase in pressure or air preheating temperature would accelerate the chemical reaction rate of each component in the combustion process, increase the flame extinction limit, and counteract the "stretching effect" of the flame, thus restraining the flame extinguishing phenomenon. The results of a path analysis show that the formation and consumption of OH had an important influence on flame extinction in the chain reaction. The net reaction rate of OH increases with increasing the initial pressure or air preheating temperature, which leads to an increase in flame intensity, combustion stability, and the extinction limit. Furthermore, the function curve between the reaction influences the RIF factor and the stretch rate of the first-to-ten reactions, affected by the heat release of flame combustion, was drawn and quantitatively analyzed. Eventually, a sensitivity analysis of the flame under different working conditions was completed, which found that promoting the forward reaction R39 H + O2<=>O + OH also promotes the positive combustion as a whole when the flame was near extinction. The sensitivity coefficient of R39 in the CH4/NH3/Air flame increases with the growing initial pressure. The increasing air preheating temperature was capable of switching the reaction of R248 NH2 + OH<=>NH + H2O in the CH4/NH3/Air flame from an inhibiting reaction to a promoting reaction, while decreasing the sensitivity coefficient of inhibiting the forward reaction R10 O + CH3<=>H + CH2O, R88 OH + HO2<=>O2 + H2O, and R271 H + NO + M<=>HNO + M. Thus, the inhibition effect of flame extinction was weakened, and the positive progress of combustion was promoted.

Deep-learning radiomics based on ultrasound can objectively evaluate thyroid nodules and assist in improving the diagnostic level of ultrasound physicians.

Background: The incidence rate of thyroid nodules has reached 65%, but only 5-15% of these modules are malignant. Therefore, accurately determining the benign and malignant nature of thyroid nodules can prevent unnecessary treatment. We aimed to develop a deep-learning (DL) radiomics model based on ultrasound (US), explore its diagnostic efficacy for benign and malignant thyroid nodules, and verify whether it improved the diagnostic level of physicians. Methods: We retrospectively included 1,076 thyroid nodules from 817 patients at three institutions. The radiomics and DL features of the US images were extracted and used to construct radiomics signature (Rad_sig) and deep-learning signature (DL_sig). A Pearson correlation analysis and least absolute shrinkage and selection operator (LASSO) regression analysis were used for feature selection. Clinical US semantic signature (C_US_sig) was constructed based on clinical information and US semantic features. Next, a combined model was constructed based on the above three signatures in the form of a nomogram. The model was constructed using a development set (institution 1: 719 nodules), and the model was evaluated using two external validation sets (institution 2: 74 nodules, and institution 3: 283 nodules). The performance of the model was assessed using decision curve analysis (DCA) and calibration curves. Furthermore, the C_US_sigs of junior physicians, senior physicians, and expers were constructed. The DL radiomics model was used to assist the physicians with different levels of experience in the interpretation of thyroid nodules. Results: In the development and validation sets, the combined model showed the highest performance, with areas under the curve (AUCs) of 0.947, 0.917, and 0.929, respectively. The DCA results showed that the comprehensive nomogram had the best clinical utility. The calibration curves indicated good calibration for all models. The AUCs for distinguishing between benign and malignant thyroid nodules by junior physicians, senior physicians, and experts were 0.714-0.752, 0.740-0.824, and 0.891-0.908, respectively; however, with the assistance of DL radiomics, the AUCs reached 0.858-0.923, 0.888-0.944, and 0.912-0.919, respectively. Conclusions: The nomogram based on DL radiomics had high diagnostic efficacy for thyroid nodules, and DL radiomics could assist physicians with different levels of experience to improve their diagnostic level.

In vitro study of ATP1A3 p.Ala275Pro mutant causing alternating hemiplegia of childhood and rapid-onset dystonia-parkinsonism.

Introduction: We previously reported that ATP1A3 c.823G>C (p.Ala275Pro) mutant causes varying phenotypes of alternative hemiplegia of childhood and rapid-onset dystonia-parkinsonism in the same family. This study aims to investigate the function of ATP1A3 c.823G>C (p.Ala275Pro) mutant at the cellular and zebrafish models. Methods: ATP1A3 wild-type and mutant Hela cell lines were constructed, and ATP1A3 mRNA expression, ATP1A3 protein expression and localization, and Na+-K+-ATPase activity in each group of cells were detected. Additionally, we also constructed zebrafish models with ATP1A3 wild-type overexpression (WT) and p.Ala275Pro mutant overexpression (MUT). Subsequently, we detected the mRNA expression of dopamine signaling pathway-associated genes, Parkinson's disease-associated genes, and apoptosisassociated genes in each group of zebrafish, and observed the growth, development, and movement behavior of zebrafish. Results: Cells carrying the p.Ala275Pro mutation exhibited lower levels of ATP1A3 mRNA, reduced ATP1A3 protein expression, and decreased Na+-K+-ATPase activity compared to wild-type cells. Immunofluorescence analysis revealed that ATP1A3 was primarily localized in the cytoplasm, but there was no significant difference in ATP1A3 protein localization before and after the mutation. In the zebrafish model, both WT and MUT groups showed lower brain and body length, dopamine neuron fluorescence intensity, escape ability, swimming distance, and average swimming speed compared to the control group. Moreover, overexpression of both wild-type and mutant ATP1A3 led to abnormal mRNA expression of genes associated with the dopamine signaling pathway and Parkinson's disease in zebrafish, and significantly upregulated transcription levels of bad and caspase-3 in the apoptosis signaling pathway, while reducing the transcriptional level of bcl-2 and the bcl-2/bax ratio. Conclusion: This study reveals that the p.Ala275Pro mutant decreases ATP1A3 protein expression and Na+/K+-ATPase activity. Abnormal expression of either wild-type or mutant ATP1A3 genes impairs growth, development, and movement behavior in zebrafish.

Inhibitory effects of cold plasma-activated water on the generation of advanced glycation end products and methylimidazoles in cookies and mechanistic evaluation using electron paramagnetic resonance.

The inhibitory effects of cold plasma-activated water (PAW) on the formation of AGEs and methylimidazoles in cookies was examined. The results showed that different PAW (parameters: 50 W-50 s, 50 W-100 s, 50 W-150 s, 100 W-50 s, 100 W-100 s, and 100 W-150 s) reduced the contents of AGEs and methylimidazoles, in which the maximum inhibition rates were 47.38% and 40.17% for free and bound AGEs and 44.16% and 40.31% for free and bound methylimidazoles, respectively. Moreover, the mechanisms associated with the elimination of carbonyl intermediates and free radicals was determined by electron paramagnetic resonance (EPR) and high performance liquid chromatography-ultraviolet/visible absorption detector (HPLC-UV/Vis). The results showed the quenching of total free radicals, alkyl free radicals, and HO· by PAW, leading to the suppression of glyoxal and methylglyoxal intermediates. These findings support PAW as a promising agent to enhance the safety of cookies.

Fabrication and characterization of TPGS-modified chlorogenic acid liposomes and its bioavailability in rats.

Chlorogenic acid (CGA), a polyphenol compound, exhibits excellent anti-oxidative, anti-hypoxic, antibacterial, antiviral, and anti-inflammatory activities, however the bioactivity of it has not been fully utilized in vivo due to its instability and low bioavailability. To address these issues, we prepared and characterized CGA-TPGS-LP, which is a TPGS-modified liposome loaded with CGA. The pharmacokinetics of CGA-TPGS-LP were studied in rats after oral administration. CGA-TPGS-LP was fabricated using a combination of thin film dispersion and ion-driven methods. The liposomes were observed to be uniformly small and spherical in shape. Their membranes were composed of lecithin, cholesterol, and TPGS lipophilic head with a TPGS hydrophilic tail chain coating on its surface. The loading efficiency and encapsulation efficiency were found to be 11.21% and 83.22%, respectively. The physicochemical characterisation demonstrated that the CGA was present in an amorphous form and retained its original structural state within the liposomal formulation. The stability of CGA was significantly improved by fabricating TPGS-LP. CGA-TPGS-LP exhibited good sustained-release properties in both simulated gastric and intestinal fluids. Following oral administration, ten metabolites were identified in rat plasma using UPLC-QTOF-MS. UPLC-QqQ-MS/MS quantitative analysis demonstrated that the oral bioavailability of CGA encapsulated in TPGS-modified liposomes was enhanced by 1.52 times. In addition, the three main metabolites of CGA had higher plasma concentrations and slower degradation rate. These results demonstrate that TPGS-modified liposomes could be a feasible strategy to further enhance the oral bioavailability of CGA, facilitating its clinical use.

Understanding the sources, function, and irreplaceable role of cobamides in organohalide-respiring bacteria.

Halogenated organic compounds are persistent pollutants that pose a serious threat to human health and the safety of ecosystems. Cobamides are essential cofactors for reductive dehalogenases (RDase) in organohalide-respiring bacteria (OHRB), which catalyze the dehalogenation process. This review systematically summarizes the impact of cobamides on organohalide respiration. The catalytic processes of cobamide in dehalogenation processes are also discussed. Additionally, we examine OHRB, which cannot synthesize cobamide and must obtain it from the environment through a salvage pathway; the co-culture with cobamide producer is more beneficial and possible. This review aims to help readers better understand the importance and function of cobamides in reductive dehalogenation. The presented information can aid in the development of bioremediation strategies.

Impact of Gold-Standard Label Errors on Evaluating Performance of Deep Learning Models in Diabetic Retinopathy Screening: Nationwide Real-World Validation Study.

BACKGROUND: For medical artificial intelligence (AI) training and validation, human expert labels are considered the gold standard that represents the correct answers or desired outputs for a given data set. These labels serve as a reference or benchmark against which the model's predictions are compared. OBJECTIVE: This study aimed to assess the accuracy of a custom deep learning (DL) algorithm on classifying diabetic retinopathy (DR) and further demonstrate how label errors may contribute to this assessment in a nationwide DR-screening program. METHODS: Fundus photographs from the Lifeline Express, a nationwide DR-screening program, were analyzed to identify the presence of referable DR using both (1) manual grading by National Health Service England-certificated graders and (2) a DL-based DR-screening algorithm with validated good lab performance. To assess the accuracy of labels, a random sample of images with disagreement between the DL algorithm and the labels was adjudicated by ophthalmologists who were masked to the previous grading results. The error rates of labels in this sample were then used to correct the number of negative and positive cases in the entire data set, serving as postcorrection labels. The DL algorithm's performance was evaluated against both pre- and postcorrection labels. RESULTS: The analysis included 736,083 images from 237,824 participants. The DL algorithm exhibited a gap between the real-world performance and the lab-reported performance in this nationwide data set, with a sensitivity increase of 12.5% (from 79.6% to 92.5%, P<.001) and a specificity increase of 6.9% (from 91.6% to 98.5%, P<.001). In the random sample, 63.6% (560/880) of negative images and 5.2% (140/2710) of positive images were misclassified in the precorrection human labels. High myopia was the primary reason for misclassifying non-DR images as referable DR images, while laser spots were predominantly responsible for misclassified referable cases. The estimated label error rate for the entire data set was 1.2%. The label correction was estimated to bring about a 12.5% enhancement in the estimated sensitivity of the DL algorithm (P<.001). CONCLUSIONS: Label errors based on human image grading, although in a small percentage, can significantly affect the performance evaluation of DL algorithms in real-world DR screening.

Exploring the heart-brain and brain-heart axis: Insights from a bidirectional Mendelian randomization study on brain cortical structure and cardiovascular disease.

INTRODUCTION: The bidirectional relationship between the brain cortex and cardiovascular diseases (CVDs) remains inadequately explored. METHODS: This study employed bidirectional Mendelian randomization (MR) analysis to investigate the interaction between nine phenotypes, namely hypertension, heart failure, atrial fibrillation (AF), and coronary heart disease (CHD), and brain cortex measurements, including total surface area (SA), average thickness (TH), and the SA and TH of 34 regions based on the Desikan-Killiany atlas. The nine traits were obtained from sources such as the UK Biobank and FinnGen, etc., while MRI-derived traits of cortical structure were sourced from the ENIGMA Consortium. The primary estimate was obtained using the inverse-variance weighted approach. False discovery rate adjustment was applied to p-values (q-values) in the analyses for regional cortical structure. RESULTS: A total of 1260 two-sample MR analyses were conducted. Existing CHD demonstrated an influence on the SA of the banks of the superior temporal sulcus (bankssts) (q = 0.018) and the superior frontal lobe (q = 0.018), while hypertension was associated with changes in the TH of the lateral occipital region (q = 0.02). Regarding the effects of the brain cortex on CVD incidence, total SA was significantly associated with the risk of CHD. Additionally, 15 regions and four areas exhibited significant effects on blood pressure and AF risk, respectively (q < 0.05). These regions were primarily located in the frontal, temporal, and cingulate areas, which are responsible for cognitive function and mood regulation. CONCLUSION: The detection of cortical changes through MRI could aid in screening for potential neuropsychiatric disorders in individuals with established CVD. Moreover, abnormalities in cortical structure may predict future CVD risk, offering new insights for prevention and treatment strategies.

Expert consensus on the diagnosis and treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia in children.

BACKGROUND: Mycoplasma pneumoniae (M. pneumoniae) is a significant contributor to community-acquired pneumonia among children. Since 1968, when a strain of M. pneumoniae resistant to macrolide antibiotics was initially reported in Japan, macrolide-resistant M. pneumoniae (MRMP) has been documented in many countries worldwide, with varying incidence rates. MRMP infections lead to a poor response to macrolide antibiotics, frequently resulting in prolonged fever, extended antibiotic treatment, increased hospitalization, intensive care unit admissions, and a significantly higher proportion of patients receiving glucocorticoids or second-line antibiotics. Since 2000, the global incidence of MRMP has gradually increased, especially in East Asia, which has posed a serious challenge to the treatment of M. pneumoniae infections in children and attracted widespread attention from pediatricians. However, there is still no global consensus on the diagnosis and treatment of MRMP in children. METHODS: We organized 29 Chinese experts majoring in pediatric pulmonology and epidemiology to write the world's first consensus on the diagnosis and treatment of pediatric MRMP pneumonia, based on evidence collection. The evidence searches and reviews were conducted using electronic databases, including PubMed, Embase, Web of Science, CNKI, Medline, and the Cochrane Library. We used variations in terms for "macrolide-resistant", "Mycoplasma pneumoniae", "MP", "M. pneumoniae", "pneumonia", "MRMP", "lower respiratory tract infection", "Mycoplasma pneumoniae infection", "children", and "pediatric". RESULTS: Epidemiology, pathogenesis, clinical manifestations, early identification, laboratory examination, principles of antibiotic use, application of glucocorticoids and intravenous immunoglobulin, and precautions for bronchoscopy are highlighted. Early and rapid identification of gene mutations associated with MRMP is now available by polymerase chain reaction and fluorescent probe techniques in respiratory specimens. Although the resistance rate to macrolide remains high, it is fortunate that M. pneumoniae still maintains good in vitro sensitivity to second-line antibiotics such as tetracyclines and quinolones, making them an effective treatment option for patients with initial treatment failure caused by macrolide antibiotics. CONCLUSIONS: This consensus, based on international and national scientific evidence, provides scientific guidance for the diagnosis and treatment of MRMP in children. Further studies on tetracycline and quinolone drugs in children are urgently needed to evaluate their effects on the growth and development. Additionally, developing an antibiotic rotation treatment strategy is necessary to reduce the prevalence of MRMP strains.

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This study presents a multi-center clinical data management platform that facilitates unified and structured management of real-world data and serves as an ideal tool to enhance the quality and progress of clinical research related to severe acute pancreatitis (SAP). The use of the platform enables clinical teams to obtain safe, accurate, structurally unified, traceable, scene-clear, and fully functional real-world medical data in the diagnosis, treatment, and research of acute pancreatitis (AP).

Reuterin promotes pyroptosis in hepatocellular cancer cells through mtDNA-mediated STING activation and caspase 8 expression.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer with poor prognosis. The available drugs for advanced HCC are limited and substantial therapeutic advances including new drugs and new combination therapies are still in urgent need. In this study, we found that the major metabolite of Lactobacillus reuteri (L. reuteri), reuterin showed great anti-HCC potential and could help in sorafenib treatment. Reuterin treatment impaired mitophagy and caused the aberrant clustering of mitochondrial nucleoids to block mitochondrial DNA (mtDNA) replication and mitochondrial fission, which could promote mtDNA leakage and subsequent STING activation in HCC cells. STING could activate pyroptosis and necroptosis, while reuterin treatment also induced caspase 8 expression to inhibit necroptosis through cleaving RIPK3 in HCC cells. Thus, pyroptosis was the main death form in reuterin-treated HCC cells and STING suppression remarkably rescued the growth inhibitory effect of reuterin and concurrently knockdown caspase 8 synergized to restrain the induction of pyroptosis. In conclusion, our study explains the detailed molecular mechanisms of the antitumor effect of reuterin and reveals its potential to perform as a combinational drug for HCC treatment.

Prevalence and genotype distribution of human papillomavirus infection among 66000 women from 2014 to 2023 in the plateau region of Southwest China.

BACKGROUND: Persistent infection with high-risk human papillomavirus (HR-HPV) plays a key role in the onset of cervical cancer. This study was designed to examine the epidemiological trends and genotype distribution of HPV from 2014 to 2023 in the plateau region of Southwest China. METHODS: The findings could offer valuable insights for clinical screening of cervical cancer and the formulation of HPV vaccination policies. This retrospective study analyzed 66,000 women who received HPV-DNA testing at the First People's Hospital of Qujing, Yunnan, China, between 2014 and 2023. The cohort consisted of 33,512 outpatients, 3,816 inpatients, and 28,672 individuals undergoing health examinations. Cervical cells were collected for DNA extraction, and PCR amplification along with Luminex xMAP technology were used to detect 27 HPV genotypes. The data analysis was conducted using GraphPad Prism and IBM SPSS Statistics 27 software. RESULTS: The overall HPV infection rate at the First People's Hospital of Qujing declined from 24.92% in 2014 to 16.29% in 2023, averaging 16.02%. Specific infection rates were 18.50% among outpatients, 12.97% among inpatients, and 13.53% for health examination attendees. The predominant high-risk HPV genotypes identified were HPV52 (2.61%), HPV16 (2.06%), HPV58 (1.81%), HPV53 (1.55%), and HPV39 (1.09%). Meanwhile, the most frequent low-risk HPV genotypes were HPV6 (1.30%), HPV61 (1.21%), and HPV11 (0.85%). In HPV-positive cases, the distribution of single, double, triple, and quadruple or more infections were 79.90%, 15.17%, 3.59%, and 1.33%, respectively. The proportions of pure LR-HPV, pure HR-HPV, and mixed infections were 22.16%, 67.82%, and 10.02%, respectively. Age-specific analysis revealed a bimodal distribution of HPV infection, with the infection rate rapidly decreasing from 44.02% in the ≤ 19 age group to 19.55% in the 20-29 age group and 13.84% in the 30-39 age group, followed by a gradual increase to 14.64% in the 40-49 age group, 16.65% in the 50-59 age group, and 22.98% in the ≥ 60 age group. The coverage rates of the three available vaccines are all below 50%. The results of this study indicated a declining trend in HPV prevalence in the plateau region of Southwest China over the period from 2014 to 2023, especially in the reduction of genotypes targeted by vaccines. CONCLUSION: There were significant variations in the genotypes prevalent among different age groups, years, and patient sources within the same region. The underwhelming vaccination rates emphasize the critical need for developing either a multivalent vaccine or a personalized vaccine that targets the HPV genotypes common in the Chinese population. Furthermore, vaccinating adolescents to curb HPV infection and ensuring regular cervical cancer screenings for postmenopausal women are crucial steps.

The Interaction of Calcium-Sensing Receptor with KIF11 Enhances Cisplatin Resistance in Lung Adenocarcinoma via BRCA1/cyclin B1 pathway.

Cisplatin (DDP) is commonly used in the treatment of non-small cell lung cancer (NSCLC), including lung adenocarcinoma (LUAD), and the primary cause for its clinical inefficacy is chemoresistance. Here, we aimed to investigate a novel mechanism of chemoresistance in LUAD cells, focusing on the calcium-sensing receptor (CaSR). In this study, high CaSR expression was detected in DDP-resistant LUAD cells, and elevated CaSR expression is strongly correlated with poor prognosis in LUAD patients receiving chemotherapy. LUAD cells with high CaSR expression exhibited decreased sensitivity to cisplatin, and the growth of DDP-resistant LUAD cells was inhibited by cisplatin treatment in combination with CaSR suppression, accompanied by changes in BRCA1 and cyclin B1 protein expression both in vitro and in vivo. Additionally, an interaction between CaSR and KIF11 was identified. Importantly, suppressing KIF11 resulted in decreased protein levels of BRCA1 and cyclin B1, enhancing the sensitivity of DDP-resistant LUAD cells to cisplatin with no obvious decrease in CaSR. Here, our findings established the critical role of CaSR in promoting cisplatin resistance in LUAD cells by modulating cyclin B1 and BRCA1 and identified KIF11 as a mediator, highlighting the potential therapeutic value of targeting CaSR to overcome chemoresistance in LUAD.

Interfacial interactions of nanoscale zero-valent iron particles with clay minerals in the aquatic environments: Experimental and theoretical calculation study.

The environmental transport and fate of nanoscale zero-valent iron particles (nZVI) in soil and groundwater can be altered by their hetero-aggregation with clay mineral particles (CMP). This study examines the interactions between bare or carboxymethyl cellulose (CMC)-coated nZVI with typical CMP, specifically kaolinite and montmorillonite. Methods include co-settling experiments, aggregation kinetic studies, electron microscopy, Derjaguin-Landau-Verwey-Overbeek (DLVO) and extended DLVO (EDLVO) energy analysis, and density functional theory calculations, focusing on the pH dependency of these interactions. The EDLVO theory effectively described the interactions between nZVI and CMP in aquatic environments. Under acidic conditions (pH 3.5), the interfacial interaction between bare nZVI and kaolinite is regulated by van der Waals forces, while complexation, van der Waals forces, and electrostatic attraction govern the interaction of bare nZVI with montmorillonite, primarily depositing on the SiO face. In contrast, the positively charged AlO face and edge of CMP are the main deposition sites for CMC-coated nZVI through hydrogen bonding, van der Waals forces, and electrostatic attraction. At neutral (pH 6.5) and alkaline (pH 9.5) conditions, both bare and CMC-coated nZVI predominantly attach to the AlO face and edge, facilitated by complexation or hydrogen bonding, alongside van der Waals forces. The attachment of CMC-coated nZVI to CMP surfaces shows reversible aggregation or deposition due to the steric repulsion from the CMC coating. These findings hold significant implications for the environmental applications and risk of nZVI.

Usefulness of estimated glucose disposal rate in detecting heart failure: results from national health and nutrition examination survey 1999-2018.

BACKGROUND: Estimated glucose disposal rate (eGDR) is a novel, clinically available, and cost-effective surrogate of insulin resistance. The current study aimed to assess the association between eGDR and prevalent heart failure (HF), and further evaluate the value of eGDR in detecting prevalent HF in a general population. METHODS: 25,450 subjects from the National Health and Nutrition Examination Survey 1999-2018 were included. HF was recorded according to the subjects' reports. Logistic regression was employed to analyze the association between eGDR and HF, the results were summarized as Per standard deviation (SD) change. Then, subgroup analysis tested whether the main result from logistic regression was robust in several conventional subpopulations. Finally, receiver-operating characteristic curve (ROC) and reclassification analysis were utilized to evaluate the potential value of eGDR in improving the detection of prevalent HF. RESULTS: The prevalence of reported HF was 2.96% (753 subjects). After adjusting demographic, laboratory, anthropometric, and medical history data, each SD increment of eGDR could result in a 43.3% (P < 0.001) risk reduction for prevalent HF. In the quartile analysis, the top quartile had a 31.1% (P < 0.001) risk of prevalent HF compared to the bottom quartile in the full model. Smooth curve fitting demonstrated that the association was linear in the whole range of eGDR (P for non-linearity = 0.313). Subgroup analysis revealed that the association was robust in age, sex, race, diabetes, and hypertension subgroups (All P for interaction > 0.05). Additionally, ROC analysis displayed a significant improvement in the detection of prevalent HF (0.869 vs. 0.873, P = 0.008); reclassification analysis also confirmed the improvement from eGDR (All P < 0.001). CONCLUSION: Our study indicates that eGDR, a costless surrogate of insulin resistance, may have a linear and robust association with the prevalent HF. Furthermore, our findings implicate the potential value of eGDR in refining the detection of prevalent HF in the general population.

Efficacy of robot-assisted thoracoscopic surgery in the treatment of pulmonary sequestration in children.

Objective: This study was performed to evaluate the efficacy of robot-assisted thoracoscopic surgery (RATS) in the treatment of pulmonary sequestration (PS) in children. Methods: All video-assisted thoracoscopic surgery (VATS) and RAST performed on patients with PS at a single center from May 2019 to July 2023 were identified. The χ 2 and Wilcoxon tests were used to compare the perioperative outcomes between VATS and RATS groups. Results: Ninety-three patients underwent RATS while 77 patients underwent VATS. In both two groups, one patient converted to thoracotomy and no surgical mortality case. The median operation time was longer for the RATS group compared with the VATS group (75 min vs. 60 min, p <0.001). A lower ratio of chest tube indwelling (61.3% vs. 90.9%, p <0.001), fewer drainage days (1.0 day vs. 2.0 days, p <0.001), and a shorter postoperative length of stay (5.0 days vs. 6.0 days, p <0.001) were found in the RATS group than that in the VATS group. No significant difference was found in the incidence of short-term postoperative complications (hydrothorax and pneumothorax) between two groups. Conclusions: RATS was safe and effective in children with PS over 6 months old and more than 7 kg. Furthermore, RATS led to better short-time postoperative outcome than VATS. Multi-institutional studies are warranted to compare differences in long-term outcomes between RATS and VATS.

Targeting BRD4 to attenuate RANKL-induced osteoclast activation and bone erosion in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that can cause destruction of cartilage and bone's extracellular matrix. Bromodomain 4 (BRD4), as a transcriptional and epigenetic regulator, plays a key role in cancer and inflammatory diseases. While, the role of BRD4 in bone destruction in RA has not been extensively reported. Our study aimed to investigate the effect of BRD4 on the bone destruction in RA and, further, its mechanism in the pathogenesis of the disease. In this study, receiving approval from the Ethical Committee of the Affiliated Hospital of Qingdao University, we evaluated synovial tissues from patients with RA and OA for BRD4 expression through advanced techniques such as immunohistochemistry, quantitative real-time PCR (qRT-PCR), and Western blotting. We employed a collagen-induced arthritis (CIA) mouse model to assess the therapeutic efficacy of the BRD4 inhibitor JQ1 on disease progression and bone destruction, supported by detailed clinical scoring and histological examinations. Further, in vitro osteoclastogenesis assays using RAW264.7 macrophages, facilitated by TRAP staining and resorption pit assays, provided insights into the mechanistic effects of JQ1 on osteoclast function. Statistical analysis was rigorously conducted using SPSS, applying Kruskal-Wallis, one-way ANOVA, and Student's t-tests to validate the data. In our study, we found that BRD4 expression significantly increased in the synovial tissues of RA patients and the ankle joints of CIA mice, with JQ1, a BRD4 inhibitor, effectively reducing inflammation, arthritis severity (p < 0.05), and bone erosion. Treatment with JQ1 not only improved bone mass and structural integrity in CIA mice but also downregulated osteoclast-related gene expression and the RANKL/RANK signaling pathway, indicating a suppression of osteolysis. Furthermore, in vitro assays demonstrated that JQ1 markedly inhibited osteoclast differentiation and function, underscoring the pivotal role of BRD4 in osteoclastogenesis and its potential as a target for therapeutic intervention in RA-induced bone destruction. Our study concludes that targeting BRD4 with the inhibitor JQ1 significantly mitigates inflammation and bone destruction in rheumatoid arthritis, suggesting that inhibition of BRD4 may be a potential therapeutic strategy for the treatment of bone destruction in RA.

Prognostic Value of S100 Family mRNA Expression in Hepatocellular Carcinoma.

BACKGROUND/AIMS:  The S100 family contains more than 20 Ca2+-binding proteins that participate in numerous cellular biological processes. However, the prognostic value of individual S100s in hepatocellular carcinoma (HCC) remains unclear. Therefore, we comprehensively assessed the prognostic value of S100s in HCC. MATERIALS AND METHODS:  The mRNA level of S100s in distinct types of cancer was analyzed through Oncomine. The clinical prognostic significance of each S100 was evaluated using Kaplan-Meier plotter and OncoLnc. The expression and mutation of S100s were determined through cBioPortal. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were used to predict the functions and pathways of S100s. RESULTS:  The analyses revealed that, relative to normal tissues, liver cancer tissues showed aberrant mRNA expression of most S100s. In the survival analysis with Kaplan-Meier plotter, elevated expression levels of S100PBP, S100A2, S100A7, S100A10, and S100A13 were related to shorter overall survival (OS), whereas increased S100A5 expression was associated with longer OS. Moreover, results obtained using OncoLnc showed that increased expression levels of S100P, S100PBP, S100A13, S100A11, S100A10, and S100A2 were related to shorter OS. Thus, S100PBP, S100A13, S100A10, and S100A2 exhibited the same prognostic trend in the 2 databases. However, all S100 member gene mutational changes had no considerable prognostic value in OS and disease-free survival of HCC patients. CONCLUSION:  Although the findings need to be further confirmed by experiments, they provide new evidence for the prognostic significance of the S100s in HCC.