Association of hemoglobin glycation index with clinical outcomes in patients with coronary artery disease: a prospective cohort study.

BACKGROUND: To analyze the association between the hemoglobin glycation index (HGI) and the long-term prognosis of patients with coronary artery disease (CAD). METHODS: HGI represented the difference between laboratory measured Hemoglobin A1c (HbA1c) and predicted HbA1c based on a liner regression between Hb1Ac and fasting plasma glucose (FPG). A total of 10 598 patients who treated with percutaneous coronary intervention (PCI) were stratified into three groups (low HGI group: HGI<-0.506, medium HGI group: -0.506 ≤ HGI < 0.179, and high HGI group: HGI ≥ 0.179). The primary endpoints includes all-cause mortality (ACM) and cardiac mortality (CM). The secondary endpoints were major adverse cardiac events (MACEs) and major adverse cardiac and cerebrovascular events (MACCEs). RESULTS: A total of 321 ACMs, 243 CMs, 774 MACEs, and 854 MACCEs were recorded during a 60-month follow-up period. After adjusting for confounders using a multivariate Cox regression analysis, the patients in the low HGI group had a significantly increased risk of ACM (adjusted HR = 1.683, 95%CI:1.179-2.404, P = 0.004) and CM (HR = 1.604, 95%CI:1.064-2.417, P = 0.024) as compared with patients in the medium HGI group. Similarly, the patients in the high HGI group had an increased risk of MACEs (HR = 1.247, 95% CI: 1.023-1.521, P = 0.029) as compared with patients in the medium HGI group. For ACM, CM, and MACEs, a U-shaped relation were found among these three groups. However, we did not find significant differences in the incidence of MACCEs among these three groups. CONCLUSION: The present study indicates that HGI could be an independent predictor for the risk of mortality and MACEs in patients with CAD.

Bone marrow mesenchymal stem cells-derived exosomal miR-381 alleviates lung ischemia-reperfusion injury by activating Treg differentiation through inhibiting YTHDF1 expression.

AIM: Our study aimed to investigate whether BMSCs-derived exosomal miR-381 promotes Treg cell differentiation in lung ischemia-reperfusion injury (LIRI), and the underlying mechanism. METHODS: The in vitro and in vivo models of LIRI were established by hypoxia/reoxygenation (H/R) treatment and lung ischemia/reperfusion (I/R) surgery, respectively. BMSCs-derived exosomes were isolated and identified by western blot, nanoparticle tracking analysis, and transmission electron microscopy. Cell viability, proliferation, and apoptosis were assessed by CCK-8, EdU, and flow cytometry assay, respectively. IL-18 secretion level in lung microvascular endothelial cells (LMECs) and lung tissue homogenate was examined by ELISA. Treg cell differentiation was determined using flow cytometry. The relationships between miR-381, YTHDF1, and IL-18 were investigated using dual-luciferase reporter gene, RIP, and/or RNA pull-down assays. MeRIP assay was employed to determine m6A modification of IL-18 mRNA in LMECs. The ubiquitination level of Foxp3 protein in CD4+ T cells was analyzed by Co-IP assay. RESULTS: BMSCs-derived exosomes reduced LMECs injury and increased Treg cell differentiation in LIRI, whereas miR-381 inhibition in BMSCs weakened these impacts. Mechanistically, miR-381 inhibited IL-18 translation in LMECs by inhibiting YTHDF1 expression via binding to its 3'-UTR. As expected, YTHDF1 overexpression in LMECs abolished the effects of miR-381-overexpressed exosomes on LMECs injury and Treg cell differentiation. Moreover, LMECs-secreted IL-18 inhibited Treg cell differentiation by promoting the ubiquitination degradation of Foxp3 protein. CONCLUSION: BMSCs-derived exosomal miR-381 suppressed IL-18 translation in LMECs through binding to YTHDF1 3'-UTR, thus suppressing the ubiquitination degradation of Foxp3 in CD4+ T cells, which promoted Treg cell differentiation and mitigated LIRI development.

Passivation performance of Nb microalloyed rebar in concrete carbonation environments with different pH.

In this study, XPS sputtering depth, SEM and electrochemical tests (CV, EIS, M-S, i-t, DPP) were used to study the structural composition and formation mechanism of surface passive film of Nb microalloyed rebar in SCPS with different pH. The results showed that after passivation for 10 d in SCPS with different pH, compared with CS rebar, the stability and compactness of surface passive film of 34Nb rebar gradually increased with the decreases of pH. Firstly, with the decreases of pH, the outer layer of surface passive film of 34Nb rebar was composed of Fe oxides and Fe hydroxides, and the inner layer was composed of Fe oxides and Nb oxides, thus increasing the mass ratio of Fe3+/Fe2+ and Nb2O5/(NbO2 + NbO). Secondly, with the decreases of pH, the addition of Nb promoted the formation of Fe oxides in 34Nb rebar, obtaining the excellent Rct, Ecorr and Ep. Finally, with the decreases of pH, the addition of Nb promoted the enrichment of Nb oxides in 34Nb rebar, inhibiting the degradation of Fe oxides, and the passive film exhibited the P-N type semiconductor, thus significantly decreasing the carrier density and enhancing the passivation rate of 34Nb rebar.

AI-based IsAb2.0 for antibody design.

Therapeutic antibody design has garnered widespread attention, highlighting its interdisciplinary importance. Advancements in technology emphasize the critical role of designing nanobodies and humanized antibodies in antibody engineering. However, current experimental methods are costly and time-consuming. Computational approaches, while progressing, faced limitations due to insufficient structural data and the absence of a standardized protocol. To tackle these challenges, our lab previously developed IsAb1.0, an in silico antibody design protocol. Yet, IsAb1.0 lacked accuracy, had a complex procedure, and required extensive antibody bioinformation. Moreover, it overlooked nanobody and humanized antibody design, hindering therapeutic antibody development. Building upon IsAb1.0, we enhanced our design protocol with artificial intelligence methods to create IsAb2.0. IsAb2.0 utilized AlphaFold-Multimer (2.3/3.0) for accurate modeling and complex construction without templates and employed the precise FlexddG method for in silico antibody optimization. Validated through optimization of a humanized nanobody J3 (HuJ3) targeting HIV-1 gp120, IsAb2.0 predicted five mutations that can improve HuJ3-gp120 binding affinity. These predictions were confirmed by commercial software and validated through binding and neutralization assays. IsAb2.0 streamlined antibody design, offering insights into future techniques to accelerate immunotherapy development.

The Impact of Leisure-Time Physical Activity and Sedentary Behavior on Mortality in Patients with Chronic Obstructive Pulmonary Disease.

OBJECTIVE: This study sought to examine the association between inactive time, leisure-time physical activity (LTPA), and mortality in individuals diagnosed with chronic obstructive pulmonary disease (COPD). DESIGN: This study utilized a nationally representative sample of patients with COPD from National Health and Nutrition Examination Survey (NHANES) survey (n = 1817; weighted population, 23,698,840). Mortality was tracked from the date of interview and examination. LTPA and sedentary time were assessed using a Global Physical Activity Questionnaire. RESULTS: The study found that only 28% of patients with COPD achieved sufficient LTPA (LTPA ≥150 min/week), while 58% reported no physical activity and 47% sat for over six hours per day. Over a nine-year follow-up period, 501 deaths occurred, with 101 due to heart diseases. Adequate LTPA levels were associated with a decreased risk of mortality from any cause. Moreover, patients who engaged in sufficient LTPA and reduced sitting time had a lower risk of mortality from any cause compared to those who did not engage in sufficient LTPA. CONCLUSION: Participating in an adequate amount of LTPA was linked to a reduced risk of death from any cause in patients with COPD. However, irrespective of the extent of the LTPA, there was no significant correlation between sedentary behavior and the risk of mortality.

The U -shape relationship between free fatty acid level and adverse outcomes in coronary artery disease patients with hypertension: evidence from a large prospective cohort study.

BACKGROUND: Evidence is scarce on the effect of free fatty acid (FFA) level in the prognosis of coronary artery disease (CAD) patients with hypertension. This study. METHODS: A large prospective cohort study with a follow-up period of average 2 years was conducted at Xinjiang Medical University Affiliated First Hospital from December 2016 to October 2021. A total of 10,395 CAD participants were divided into groups based on FFA concentration and hypertension status, and then primary outcome mortality and secondary endpoint ischemic events were assessed in the different groups. RESULTS: A total of 222 all-cause mortality (ACMs), 164 cardiac mortality (CMs), 718 major adverse cardiovascular events (MACEs) and 803 major adverse cardiovascular and cerebrovascular events (MACCEs) were recorded during follow-up period. A nonlinear relationship between FFA and adverse outcomes was observed only in CAD patients with hypertension. Namely, a "U -shape" relationship between FFA levels and long-term outcomes was found in CAD patients with hypertension. Lower FFA level (< 310 µmol/L), or higher FFA level (≥ 580 µmol/L) at baseline is independent risk factors for adverse outcomes. After adjustment for confounders, excess FFA increases mortality (ACM, HR = 1.957, 95%CI(1.240-3.087), P = 0.004; CM, HR = 2.704, 95%CI(1.495-4.890, P = 0.001) and MACE (HR = 1.411, 95%CI(1.077-1.848), P = 0.012), MACCE (HR = 1.299, 95%CI (1.013-1.666), P = 0.040) prevalence. Low levels of FFA at baseline can also increase the incidence of MACE (HR = 1.567,95%CI (1.187-2.069), P = 0.002) and MACCE (HR = 1.387, 95%CI (1.070-1.798), P = 0.013). CONCLUSIONS: Baseline FFA concentrations significantly associated with long-term mortality and ischemic events could be a better and novel risk biomarker for prognosis prediction in CAD patients with hypertension. TRIAL REGISTRATION: The details of the design were registered on https://www.chictr.org.cn/ (Identifier NCT05174143).

Association of the Triglyceride-Glucose Index With Resistant Hypertension and a Nomogram Model Construction.

BACKGROUND: Resistant hypertension (RH) remains one of the major risk factors for cardiovascular disease. This study aims to investigate the association between the triglyceride-glucose (TyG) index and RH incidence in patients with hypertension and to construct a nomogram for predicting the occurrence of RH. METHODS AND RESULTS: A retrospective cohort study was conducted on 1635 patients initially diagnosed with hypertension at the Affiliated Traditional Chinese Medicine Hospital of Xinjiang Medical University from August 2019 to August 2021. Patients were followed up for a median of 31 months, with 373 cases (22.81%) developing RH. Least absolute shrinkage and selection operator regression and multivariable Cox regression analysis identified the TyG index as the strongest predictor of RH (hazard ratio, 5.472 [95% CI, 4.028-7.433]; P<0.001). Consistent results were also observed in subgroup analyses across different ages and sexes. In addition to the TyG index, other independent risk factors, including uric acid, age, and the apnea-hypopnea index, were noted. A nomogram model was subsequently developed using these risk factors, and including the TyG index notably enhanced the diagnostic effectiveness of the model in predicting the occurrence of RH. CONCLUSIONS: The TyG index appears to be a potential predictor of RH in patients with hypertension, indicating that insulin resistance might be an important factor in the development and progression of RH.

Prescribed Fixed-Time Control for Constrained Uncertain Nonlinear Cyber-Physical Systems Against Deception Attacks.

In this note, a novel prescribed fixed-time adaptive tracking control scheme is developed to cope with the fixed-time tracking control issue for a category of constrained MIMO nonlinear cyber-physical systems (CPSs) with exogenous perturbations, which suffer from deception attacks started in controller-actuator (C-A) channel. Distinguished from the conservative dynamic surface control (DSC) schemes with a linear filter, a novel nonlinear filter is designed in our strategy, which can tackle the intrinsic issue of explosion of computational complexity and promote the system performance. Besides, a new barrier Lyapunov function (BLF) is designed to ulteriorly enhance the tracking performance on the basis of the prescribed performance function (PPF) approach. Prominently, the proposed control strategy could accommodate the exogenous interferences and deception attacks simultaneously. Furthermore, we have substantiated that the developed approach can not only make certain that all the tracking errors of the resulting closed-loop system, including output tracking errors and virtual tracking errors, enter a prespecified small region near equilibrium point with fixed-time convergence rate, but also guarantee them obey the corresponding constraints throughout the entire control operation, where the regulation time and the tracking accuracy level keep prior known and could be prespecified arbitrarily. Finally, the validity and effectiveness of the proposed control scheme are illustrated through a representative application instance.

Comparative Metabolome and Transcriptome Analysis of Rapeseed (Brassica napus L.) Cotyledons in Response to Cold Stress.

Cold stress affects the seed germination and early growth of winter rapeseed, leading to yield losses. We employed transmission electron microscopy, physiological analyses, metabolome profiling, and transcriptome sequencing to understand the effect of cold stress (0 °C, LW) on the cotyledons of cold-tolerant (GX74) and -sensitive (XY15) rapeseeds. The mesophyll cells in cold-treated XY15 were severely damaged compared to slightly damaged cells in GX74. The fructose, glucose, malondialdehyde, and proline contents increased after cold stress in both genotypes; however, GX74 had significantly higher content than XY15. The pyruvic acid content increased after cold stress in GX74, but decreased in XY15. Metabolome analysis detected 590 compounds, of which 32 and 74 were differentially accumulated in GX74 (CK vs. cold stress) and XY15 (CK vs. cold stressed). Arachidonic acid and magnoflorine were the most up-accumulated metabolites in GX74 subjected to cold stress compared to CK. There were 461 and 1481 differentially expressed genes (DEGs) specific to XY15 and GX74 rapeseeds, respectively. Generally, the commonly expressed genes had higher expressions in GX74 compared to XY15 in CK and cold stress conditions. The expression changes in DEGs related to photosynthesis-antenna proteins, chlorophyll biosynthesis, and sugar biosynthesis-related pathways were consistent with the fructose and glucose levels in cotyledons. Compared to XY15, GX74 showed upregulation of a higher number of genes/transcripts related to arachidonic acid, pyruvic acid, arginine and proline biosynthesis, cell wall changes, reactive oxygen species scavenging, cold-responsive pathways, and phytohormone-related pathways. Taken together, our results provide a detailed overview of the cold stress responses in rapeseed cotyledons.

Multimodal Data Integration Enhance Longitudinal Prediction of New-Onset Systemic Arterial Hypertension Patients with Suspected Obstructive Sleep Apnea.

Background: It is crucial to accurately predict the disease progression of systemic arterial hypertension in order to determine the most effective therapeutic strategy. To achieve this, we have employed a multimodal data-integration approach to predict the longitudinal progression of new-onset systemic arterial hypertension patients with suspected obstructive sleep apnea (OSA) at the individual level. Methods: We developed and validated a predictive nomogram model that utilizes multimodal data, consisting of clinical features, laboratory tests, and sleep monitoring data. We assessed the probabilities of major adverse cardiac and cerebrovascular events (MACCEs) as scores for participants in longitudinal cohorts who have systemic arterial hypertension and suspected OSA. In this cohort study, MACCEs were considered as a composite of cardiac mortality, acute coronary syndrome and nonfatal stroke. The least absolute shrinkage and selection operator (LASSO) regression and multiple Cox regression analyses were performed to identify independent risk factors for MACCEs among these patients. Results: 448 patients were randomly assigned to the training cohort while 189 were assigned to the verification cohort. Four clinical variables were enrolled in the constructed nomogram: age, diabetes mellitus, triglyceride, and apnea-hypopnea index (AHI). This model accurately predicted 2-year and 3-year MACCEs, achieving an impressive area under the receiver operating characteristic (ROC) curve of 0.885 and 0.784 in the training cohort, respectively. In the verification cohort, the performance of the nomogram model had good discriminatory power, with an area under the ROC curve of 0.847 and 0.729 for 2-year and 3-year MACCEs, respectively. The correlation between predicted and actual observed MACCEs was high, provided by a calibration plot, for training and verification cohorts. Conclusions: Our study yielded risk stratification for systemic arterial hypertension patients with suspected OSA, which can be quantified through the integration of multimodal data, thus highlighting OSA as a spectrum of disease. This prediction nomogram could be instrumental in defining the disease state and long-term clinical outcomes.

Predicting depression in patients with heart failure based on a stacking model.

BACKGROUND: There is a lack of literature discussing the utilization of the stacking ensemble algorithm for predicting depression in patients with heart failure (HF). AIM: To create a stacking model for predicting depression in patients with HF. METHODS: This study analyzed data on 1084 HF patients from the National Health and Nutrition Examination Survey database spanning from 2005 to 2018. Through univariate analysis and the use of an artificial neural network algorithm, predictors significantly linked to depression were identified. These predictors were utilized to create a stacking model employing tree-based learners. The performances of both the individual models and the stacking model were assessed by using the test dataset. Furthermore, the SHapley additive exPlanations (SHAP) model was applied to interpret the stacking model. RESULTS: The models included five predictors. Among these models, the stacking model demonstrated the highest performance, achieving an area under the curve of 0.77 (95%CI: 0.71-0.84), a sensitivity of 0.71, and a specificity of 0.68. The calibration curve supported the reliability of the models, and decision curve analysis confirmed their clinical value. The SHAP plot demonstrated that age had the most significant impact on the stacking model's output. CONCLUSION: The stacking model demonstrated strong predictive performance. Clinicians can utilize this model to identify high-risk depression patients with HF, thus enabling early provision of psychological interventions.

Low back pain in medical workers and its influencing factors.

PURPOSE: To investigate the prevalence of occupational lower back pain (OLBP) among medical workers and identify the contributing factors. METHODS: An electronic questionnaire was distributed to medical workers at Yuebei People's Hospital to gather information on various factors, including gender, age, body mass index (BMI), length of employment, job role, education level, professional title, marital status, fertility status, frequency of night shift, weight lifting daily, duration of daily standing at work, frequency of bending, work-related stress, experience with low back protection training, and frequency of waist exercises. Univariate and multivariate logistic regression analyses were conducted to identify the factors associated with OLBP in medical workers. RESULTS: Out of the 98 medical workers surveyed, 67 experienced OLBP (68.37%). The results of multivariate logistic regression analysis revealed that working for more than 5 years, holding a nursing position, and lacking training in low back protection were significant risk factors for developing OLBP in medical workers (all P<0.05). CONCLUSION: OLBP is a prevalent issue among medical workers, and various factors such as length of employment, job role, and training in low back protection can influence its occurrence.

Serum 5'-Nucleotidase as a Novel Predictor of Adverse Clinical Outcomes after Percutaneous Coronary Intervention in Patients with Coronary Artery Disease.

Background: The correlation between 5 ' -Nucleotidase ( 5 ' -NT) and the clinical outcomes in coronary artery disease (CAD) patients following percutaneous coronary intervention (PCI) is not clear. This study aims to clarify this relationship. Methods: The PRACTICE study enrolled 15,250 patients between December 2016 and October 2021. After filtering out those without 5 ' -NT data, a total of 6555 patients were analyzed with a median follow-up of 24 months. Based on the receiver operating characteristic (ROC) curve analysis, a 5 ' -NT level of 5.57 U/L was selected as the optimal cutoff value. All research samples were divided into high-value ( ≥ 5.57 U/L, n = 2346) and low-value groups ( < 5.57 U/L, n = 4209). Key clinical outcomes included all-cause death (ACD), cardiovascular death (CD), major adverse cardiovascular events (MACE), and major adverse cardiovascular and cerebrovascular events (MACCE). After separating patients into high and low value groups, multivariate Cox regression analysis was used to correct for potential confounding variables. Finally, risk ratios and their 95% confidence intervals (CIs) were calculated. Results: During the follow-up period, 129 instances of ACD were recorded-49 cases (1.2%) in the low-value group and 80 cases (3.4%) in the high-value group. Similarly, 102 CDs occurred, including 42 low-value group cases (1.0%) and 60 high-value group cases (2.6%). A total of 363 MACE occurred, including 198 low-value group cases (4.7%) and 165 high-value group cases (7%). A total of 397 cases of MACCE occurred, including 227 low-value group cases (5.4%) and 170 high-value group cases (7.2%). As serum 5 ' -NT increased, the incidence of ACD, CD, MACE and MACCE increased. After multivariate Cox regression, high 5 ' -NT levels were linked with a 1.63-fold increase in ACD risk (hazard ratio [HR] = 2.630, 95% CI: [1.770-3.908], p < 0.001) when compared to low 5 ' -NT patients. Similarly, the risk of CD, MACE, and MACCE increased by 1.298-fold (HR = 2.298, 95% CI: [1.477-3.573], p < 0.001), 41% (HR = 1.410, 95% CI: [1.124-1.768], p = 0.003) and 30.5% (HR = 1.305, 95% CI: [1.049-1.623], p = 0.017), respectively. Conclusions: high serum 5 ' -NT levels were independently correlated with adverse clinical outcomes in CAD patients following PCI, affirming its potential as a prognostic indicator.

Effect of Ce on structural evolution and corrosion resistance of HRB500E rebar corrosion layer.

HRB500E rebar is a low-alloy high-strength steel with excellent mechanical properties and good plasticity but suffers from deficient corrosion resistance. This can be solved by adding trace elements, including rare earth elements. Herein, the corrosion-resistant behavior of rebar was evaluated by weightlessness testing and electrochemical measurements, and the effects of Ce on the structural evolution of the corrosion product layer were investigated by scanning electron microscopy (SEM), Electron Probe X-ray Micro-Analyzer (EPMA), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). The results showed that adding Ce to the rebar improved the densification of the reinforcing surface corrosion products, as well as reduced the corrosion rate of the experimental rebar. Compared to C0 sample without Ce, the rebar sample containing 0.044 wt.% Ce displayed increased Ecorr by 0.051 V, decreased Icorr by 15.573 mA cm-2, enhanced Rc of the corrosion product layer by 112.71 Ω cm2, incremented α-FeOOH content in the corrosion product layer, and boosted ratio of α/γ* in the corrosion product layer by 10.11%. Furthermore, the oxide (CeO2) formed by Ce in the corrosion layer of the rebar bar surface existed in the rust layer, resulting in a stable corrosion product layer with improved blocking ability of the corrosive medium. Overall, the addition of Ce at certain ratios looks promising to produce HRB500E rebar with excellent corrosion resistance and extended service life under harsh conditions.

Association between the C-Reactive Protein-Albumin-Lymphocyte (CALLY) Index and Adverse Clinical Outcomes in CAD Patients after PCI: Findings of a Real-World Study.

Background: The C-reactive protein-albumin-lymphocyte (CALLY) index is a novel inflammatory biomarker, and its association with the prognosis of coronary artery disease (CAD) after percutaneous coronary intervention (PCI) has not previously been studied. Therefore, this study aimed to investigate the effect of using the CALLY index on adverse outcomes in CAD patients undergoing PCI. Methods: From December 2016 to October 2021, we consecutively enrolled 15,250 CAD patients and performed follow-ups for primary endpoints consisting of all-cause mortality (ACM) and cardiac mortality (CM). The CALLY index was computed using the following formula: (albumin × lymphocyte)/(C-reactive protein (CRP) × 10 4 ). The average duration of the follow-up was 24 months. Results: A total of 3799 CAD patients who had undergone PCI were ultimately enrolled in the present study. The patients were divided into four groups according to the CALLY index quartiles: Q1 ( ≤ 0.69, n = 950), Q2 (0.69-2.44, n = 950), Q3 (2.44-9.52, n = 950), and Q4 ( > 9.52, n = 949). The low-Q1 group had a significantly higher prevalence of ACM (p < 0.001), CM (p < 0.001), major adverse cardiac events (MACEs) (p = 0.002), and major adverse cardiac and cerebrovascular events (MACCEs) (p = 0.002). Kaplan-Meier analysis revealed that a low CALLY index was significantly linked with adverse outcomes. After univariate and multivariate Cox regression analysis, the risk of ACM, CM, MACEs, and MACCEs decreased by 73.7% (adjust hazard risk [HR] = 0.263, 95% CI: 0.147-0.468, p < 0.001), 70.6% (adjust HR = 0.294, 95% CI: 0.150-0.579, p < 0. 001), 37.4% (adjust HR = 0.626, 95% CI: 0.422-0.929, p = 0.010), and 41.5% (adjust HR = 0.585, 95% CI: 0.401-0.856, p = 0.006), respectively, in the Q4 quartiles compared with the Q1 quartiles. Conclusions: This study revealed that a decreased CALLY index was associated with worse prognoses for CAD patients after PCI. The categorization of patients with a decreased CALLY index could provide valuable evidence for the risk stratification of adverse outcomes in CAD patients after PCI. Clinical Trial Registration: The details are available at http://www.chictr.org.cn (Identifier: NCT05174143).

A Simple Prognostic Scoring System for Hepatocellular Carcinoma Treated with DEB-TACE.

Objective: To develop a simple and effective prognostic scoring system to predict the efficacy of drug-eluting bead-transcatheter arterial chemoembolization (DEB-TACE) in the treatment of hepatocellular carcinoma (HCC). Methods: Data were retrospectively collected from 230 patients with HCC who received DEB-TACE treatment at six medical centers between January 2019 and December 2022. We developed a predictive score based on independent risk factors for overall survival (OS), validated the model using a validation cohort, and compared its prognostic accuracy with commonly used HCC staging systems. Results: The number of tumors, albumin-bilirubin levels, alpha-fetoprotein levels, and portal vein thrombus grade were identified as independent factors influencing OS. Based on these factors, we established the DEB-TACE treatment of HCC (DTH) scoring system. The DTH score correlated well with OS, which decreased as the DTH score increased. According to the DTH score, patients were categorized into three risk groups: low-risk (DTH-A, 0-4 points), medium-risk (DTH-B, 5-6 points), and high-risk (DTH-A, 7 points). The OS of each risk group was 18.73±0.62 months, 12.73±0.10 months, and 6.93±0.19 months, respectively (p<0.001). The external cohort validation confirmed the accuracy of the DTH score, demonstrating superior predictive performance compared to other commonly used HCC scoring systems. Conclusion: The DTH-HCC scoring system effectively predicts the outcomes of HCC patients undergoing DEB-TACE as initial treatment. This model can aid in the initial planning and decision-making process for DEB-TACE treatment in HCC patients.

Identification and validation of potential common biomarkers for papillary thyroid carcinoma and Hashimoto's thyroiditis through bioinformatics analysis and machine learning.

There is a growing body of evidence suggesting that Hashimoto's thyroiditis (HT) may contribute to an increased risk of papillary thyroid carcinoma (PTC). However, the exact relationship between HT and PTC is still not fully understood. The objective of this study was to identify potential common biomarkers that may be associated with both PTC and HT. Three microarray datasets from the GEO database and RNA-seq dataset from TCGA database were collected to identify shared differentially expressed genes (DEGs) between HT and PTC. A total of 101 genes was identified as common DEGs, primarily enriched inflammation- and immune-related pathways through GO and KEGG analysis. We performed protein-protein interaction analysis and identified six significant modules comprising a total of 29 genes. Subsequently, tree hub genes (CD53, FCER1G, TYROBP) were selected using random forest (RF) algorithms for the development of three diagnostic models. The artificial neural network (ANN) model demonstrates superior performance. Notably, CD53 exerted the greatest influence on the ANN model output. We analyzed the protein expressions of the three genes using the Human Protein Atlas database. Moreover, we observed various dysregulated immune cells that were significantly associated with the hub genes through immune infiltration analysis. Immunofluorescence staining confirmed the differential expression of CD53, FCER1G, and TYROBP, as well as the results of immune infiltration analysis. Lastly, we hypothesise that benzylpenicilloyl polylysine and aspirinmay be effective in the treatment of HT and PTC and may prevent HT carcinogenesis. This study indicates that CD53, FCER1G, and TYROBP play a role in the development of HT and PTC, and may contribute to the progression of HT to PTC. These hub genes could potentially serve as diagnostic markers and therapeutic targets for PTC and HT.

Association between extremely high prognostic nutritional index and all-cause mortality in patients with coronary artery disease: secondary analysis of a prospective cohort study in China.

OBJECTIVES: Decreased prognostic nutritional index (PNI) was associated with adverse outcomes in many clinical diseases. This study aimed to evaluate the relationship between baseline PNI value and adverse clinical outcomes in patients with coronary artery disease (CAD). DESIGN: The Personalized Antiplatelet Therapy According to CYP2C19 Genotype in Coronary Artery Disease (PRACTICE) study, a prospective cohort study of 15 250 patients with CAD, was performed from December 2016 to October 2021. The longest follow-up period was 5 years. This study was a secondary analysis of the PRACTICE study. SETTING: The study setting was Xinjiang Medical University Affiliated First Hospital in China. PARTICIPANTS: Using the 50th and 90th percentiles of the PNI in the total cohort as two cut-off limits, we divided all participants into three groups: Q1 (PNI <51.35, n = 7515), Q2 (51.35 ≤ PNI < 59.80, n = 5958) and Q3 (PNI ≥ 59.80, n = 1510). The PNI value was calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm3). PRIMARY OUTCOME: The primary outcome measure was mortality, including all-cause mortality (ACM) and cardiac mortality (CM). RESULTS: In 14 983 participants followed for a median of 24 months, a total of 448 ACM, 333 CM, 1162 major adverse cardiovascular events (MACE) and 1276 major adverse cardiovascular and cerebrovascular events (MACCE) were recorded. The incidence of adverse outcomes was significantly different among the three groups (p <0.001). There were 338 (4.5%), 77 (1.3%) and 33 (2.2%) ACM events in the three groups, respectively. A restricted cubic spline displayed a J-shaped relationship between the PNI and worse 5-year outcomes, including ACM, CM, MACE and MACCE. After adjusting for traditional cardiovascular risk factors, we found that only patients with extremely high PNI values in the Q3 subgroup or low PNI values in the Q1 subgroup had a greater risk of ACM (Q3 vs Q2, HR: 1.617, 95% CI 1.012 to 2.585, p=0.045; Q1 vs Q2, HR=1.995, 95% CI 1.532 to 2.598, p <0.001). CONCLUSION: This study revealed a J-shaped relationship between the baseline PNI and ACM in patients with CAD, with a greater risk of ACM at extremely high PNI values. TRIAL REGISTRATION NUMBER: NCT05174143.

The role of perirenal adipose tissue deposition in chronic kidney disease progression: Mechanisms and therapeutic implications.

Chronic kidney disease (CKD) represents a significant and escalating global health challenge, with morbidity and mortality rates rising steadily. Evidence increasingly implicates perirenal adipose tissue (PRAT) deposition as a contributing factor in the pathogenesis of CKD. This review explores how PRAT deposition may exert deleterious effects on renal structure and function. The anatomical proximity of PRAT to the kidneys not only potentially causes mechanical compression but also leads to the dysregulated secretion of adipokines and inflammatory mediators, such as adiponectin, leptin, visfatin, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and exosomes. Additionally, PRAT deposition may contribute to renal lipotoxicity through elevated levels of free fatty acids (FFA), triglycerides (TAG), diacylglycerol (DAG), and ceramides (Cer). PRAT deposition is also linked to the hyperactivation of the renin-angiotensin-aldosterone system (RAAS), which further exacerbates CKD progression. Recognizing PRAT deposition as an independent risk factor for CKD underscores the potential of targeting PRAT as a novel strategy for the prevention and management of CKD. This review further discusses interventions that could include measuring PRAT thickness to establish a baseline, managing metabolic risk factors that promote its deposition, and inhibiting key PRAT-induced signaling pathways.

An efficient method for rapid screening of triterpenoid saponins in three Glycyrrhiza species using rapid resolution liquid chromatography quadrupole time-of-flight mass spectrometry combined with mass defect filtering.

Triterpenoid saponins, a major bioactive component of liquorice, possess high hydrophilicity and often co-occur with other impurities of similar polarity. Additionally, subtle structural differences of some triterpenoid saponins bring challenges to comprehensive characterisation. In this study, triterpenoid saponins of three Glycyrrhiza species were systematically analysed using rapid resolution liquid chromatography quadrupole time-of-flight mass spectrometry (RRLC-Q-TOF-MS) coupled with mass defect filtering (MDF). Firstly, comprehensive date acquisition was achieved using RRLC-Q-TOF-MS. Secondly, a polygonal MDF method was established by summarizing known and speculated substituents and modifications based on the core structure to rapidly screen potential triterpenoid saponins. Thirdly, based on the fragmentation patterns of reference compounds, an identification strategy for characterisation of triterpenoid saponins was proposed. The strategy divided triterpenoid saponins into three distinct classes. By this strategy, 98 triterpenoid saponins including 10 potential new ones were tentatively characterised. Finally, triterpenoid saponins of three Glycyrrhiza species were further analysed using principle component analysis (PCA) and orthogonality partial least squares discriminant analysis (OPLS-DA). Among these, 18 compounds with variable importance in projections (VIP) > 1.0 and P values < 0.05 were selected to distinguish three Glycyrrhiza species. Overall, our study provided a reference for quality control and rational use of the three species.