First-Principles Study of Penta-PtXY (X = Se, Te; Y = S, Te; X ≠ Y) Monolayer with Highly Anisotropic Electronic and Optical Properties.

Two-dimensional (2D) semiconducting materials with anisotropic physical properties have induced lively interest due to their application in the field of polarizing devices. Herein, we have designed a family of penta-PtXY (X = Se, Te; Y = S, Te; X ≠ Y) monolayers and predicted the electronic and optical properties based on the first-principles calculation. The results suggest that the penta-PtXY (X = Se, Te; Y = S, Te; X ≠ Y) monolayers are indirect-gap semiconductors with a medium bandgap of 2.29-2.66 eV. The penta-PtXY (X = Se, Te; Y = S, Te; X ≠ Y) monolayers own a remarkable mechanical anisotropy with a high Young's modulus anisotropic ratio (3.0). In addition, the penta-PtXY (X = Se, Te; Y = S, Te; X ≠ Y) monolayers exhibit a high anisotropy ratio of hole/electron mobility in the x and y directions (1.16-3.54). The results calculated by the G0W0+BSE method indicate that the single-layers also bear a salient optical anisotropy ratio (1.56-2.11). The integration of the anisotropic electronic, optical, and mechanical properties entitles penta-PtXY (X = Se, Te; Y = S, Te; X ≠ Y) monolayers as potential candidates in multifunctional polarized nanodevices.

Gasdermin D could be lost in the brain parenchyma infarct core and a pyroptosis-autophagy inhibition effect of Jie-Du-Huo-Xue decoction after stroke.

Background: The Chinese ethnic medicine Jie-Du-Huo-Xue Decoction (JDHXD) is used to alleviate neuroinflammation in cerebral ischemia (CI). Our previous studies have confirmed that JDHXD can inhibit microglial pyroptosis in CI. However, the pharmacological mechanism of JDHXD in alleviating neuroinflammation and pyroptosis needs to be further elucidated. New research points out that there is an interaction between autophagy and inflammasome NLRP3, and autophagy can help clear NLRP3. The NLRP3 is a key initiator of pyroptosis and autophagy. The effect of JDHXD promoting autophagy to clear NLRP3 to inhibit pyroptosis on cerebral ischemia-reperfusion inflammatory injury is currently unknown. We speculate that JDHXD can inhibit pyroptosis in CI by promoting autophagy to clear NLRP3. Methods: Chemical characterization of JDHXD was performed using LC-MS. Model of middle cerebral artery occlusion/reperfusion (MCAO/R) was established in SD rats. Neurological deficits, neuron damage, and cerebral infarct volume were evaluated. Western Blot and immunofluorescence were used to detect neuronal pyroptosis and autophagy. Results: 30 possible substance metabolites in JDHXD medicated serum were analyzed by LC-MS (Composite Score > 0.98). Furthermore, JDHXD protects rat neurological function and cerebral infarct size after CI. JDHXD inhibited the expression of pyroptosis and autophagy after CI. Our western blot and immunofluorescence results showed that JDHXD treatment can reduce the expression of autophagy-related factors ULK1, beclin1, and LC3-Ⅱ. The expression of NLRP3 protein was lower in the JDHXD group than in the I/R group. Compared with the I/R group, the expressions of pyroptosis-related factors caspase-1 P 10, GSDMD-NT, IL-18, and IL-1ß decreased in the JDHXD group. Furthermore, we observed an unexpected result: immunofluorescence demonstrated that Gasdermin D (GSDMD) was significantly absent in the infarct core, and highly expressed in the peri-infarct and contralateral cerebral hemispheres. This finding challenges the prevailing view that GSDMD is elevated in the ischemic cerebral hemisphere. Conclusion: JDHXD inhibited pyroptosis and autophagy after MCAO/R. JDHXD suppressed pyroptosis and autophagy by inhibiting NLRP3, thereby alleviating CI. In addition, we present a different observation from previous studies that the expression of GSDMD in the infarct core was lower than that in the peri-infarct and contralateral non-ischemic hemispheres on day 3 of CI.

Network-level crash risk analysis using large-scale geometry features.

Road traffic crashes are common occurrences that create substantial losses and hazards to society. A complex interaction of components, including drivers, vehicles, roads, and the environment, can impact the causes of these crashes. Due to its complexity, crash identification, and prediction research over large-scale areas faces several obstacles, including high costs and challenging data collecting. This study offers a method for large-scale road network crash risk identification based on open-source data, given that roadways' horizontal and vertical geometric alignment is crucial in highway traffic crashes. This methodology includes a comprehensive technique for feature extraction from horizontal curves (H-curves) and vertical curves (V-curves) and a novel way of combining the XGBoost model's attributes with the Harris Hawks Optimization (HHO) algorithm-referred to as the HHO-XGBoost model. Using this model on the road geometry-crash risk dataset developed specifically for this study, the HHO approach adaptively identifies the optimal set of XGBoost hyperparameters and yields favorable outcomes. This study creates a three-dimensional road geometry database that may be utilized for various road infrastructure management, operation, and safety in addition to completing a tiered risk analysis of "region-road-segment" for large-scale road networks. It also offers direction on using swarm intelligence algorithms in integrated learning models.

Precise and efficient measurement of tibial slope on magnetic resonance imaging (MRI): two novel autonomous pipelines by traditional and deep learning algorithms.

Background: The measurement of posterior tibial slopes (PTS) can aid in the screening and prevention of anterior cruciate ligament (ACL) injuries and improve the success rate of some other knee surgeries. However, the circle method for measuring PTS on magnetic resonance imaging (MRI) scans is challenging and time-consuming for most clinicians to implement in practice, despite being highly repeatable. Currently, there is no automated measurement scheme based on this method. To enhance measurement efficiency, consistency, and reduce errors resulting from manual measurements by physicians, this study proposes two novel, precise, and computationally efficient pipelines for autonomous measurement of PTS. Methods: The first pipeline employs traditional algorithms with experimental parameters to extract the tibial contour, detect adhesions, and then remove these adhesions from the extracted contour. A cyclic process is employed to adjust the parameters adaptively and generate a better binary image for the following tibial contour extraction step. The second pipeline utilizes deep learning models for classifying MRI slice images and segmenting tibial contours. The incorporation of deep learning models greatly simplifies the corresponding steps in pipeline 1. Results: To evaluate the practical performance of the proposed pipelines, doctors utilized MRI images from 20 patients. The success rates of pipeline 1 for central, medial, and lateral slices were 85%, 100%, and 90%, respectively, while pipeline 2 achieved success rates of 100%, 100%, and 95%. Compared to the 10 minutes required for manual measurement, our automated methods enable doctors to measure PTS within 10 seconds. Conclusions: These evaluation results validate that the proposed pipelines are highly reliable and effective. Employing these tools can effectively prevent medical practitioners from being burdened by monotonous and repetitive manual measurement procedures, thereby enhancing both the precision and efficiency. Additionally, this tool holds the potential to contribute to the researches regarding the significance of PTS, particularly those demanding extensive and precise PTS measurement outcomes.

"Urological age" as a proxy of healthy longevity: analysis of prospective population-based cohorts in U.S. and China.

BACKGROUND: Assessing urinary symptoms poses a complex challenge for primary care practitioners. In evaluating urological function, our approach involves constructing an urological age through the analysis of laboratory parameters and indicators of the urinary system. METHODS: Based on the National Health and Nutrition Examination Survey (NHANES), urological laboratory tests and age-related symptoms were included in the development of urological age (UA) and urological age acceleration (UAA) through the Klemera Doubal method. In relation to mortality associated with UAA, the metric was categorized into grades (0, 1, 2) as a discrete variable. We investigated the correlation between UAA and its grades with mortality, conducted survival analysis based on UAA grades, and explored the correlation between multisystem ageing-related disorders and UAA grades based on the NHANES and the West China Natural Population Cohort Study. RESULTS: UA was related to age with the r to 0.85 in men and 0.84 in women. Each year the increase in UAA was related to higher 1% and 4% mortality for men and women. Those with UAA grades 1 and 2 were associated with more risk of mortality than individuals with UAA grade 0 (men 8% and 40%, women 24% and 157%). The advanced UAA grades kept pace with multisystem ageing. Healthy diets and lifestyle habits are associated with lower UAA. CONCLUSION: Urological age is related to multisystem ageing and increases mortality risk, and urological age can be used to screen high-risk individuals and inform precision clinical development for ageing intervention.

Glutaminolysis is a Potential Therapeutic Target for Kidney Diseases.

Metabolic reprogramming contributes to the progression and prognosis of various kidney diseases. Glutamine is the most abundant free amino acid in the body and participates in more metabolic processes than other amino acids. Altered glutamine metabolism is a prominent feature in different kidney diseases. Glutaminolysis converts glutamine into the TCA cycle metabolite, alpha-ketoglutarate, via a cascade of enzymatic reactions. This metabolic pathway plays pivotal roles in inflammation, maladaptive repair, cell survival and proliferation, redox homeostasis, and immune regulation. Given the crucial role of glutaminolysis in bioenergetics and anaplerotic fluxes in kidney pathogenesis, studies on this cascade could provide a better understanding of kidney diseases, thus inspiring the development of potential methods for targeted therapy. Emerging evidence has shown that targeting glutaminolysis is a promising therapeutic strategy for ameliorating kidney disease. In this narrative review, equation including keywords related to glutamine, glutaminolysis and kidney are subjected to an exhaustive search on Pubmed database, we identified all relevant articles published before 1 April, 2024. Afterwards, we summarize the regulation of glutaminolysis in major kidney diseases and its underlying molecular mechanisms. Furthermore, we highlight therapeutic strategies targeting glutaminolysis and their potential clinical applications.

Dual Attention-Based 3D U-Net Liver Segmentation Algorithm on CT Images.

The liver is a vital organ in the human body, and CT images can intuitively display its morphology. Physicians rely on liver CT images to observe its anatomical structure and areas of pathology, providing evidence for clinical diagnosis and treatment planning. To assist physicians in making accurate judgments, artificial intelligence techniques are adopted. Addressing the limitations of existing methods in liver CT image segmentation, such as weak contextual analysis and semantic information loss, we propose a novel Dual Attention-Based 3D U-Net liver segmentation algorithm on CT images. The innovations of our approach are summarized as follows: (1) We improve the 3D U-Net network by introducing residual connections to better capture multi-scale information and alleviate semantic information loss. (2) We propose the DA-Block encoder structure to enhance feature extraction capability. (3) We introduce the CBAM module into skip connections to optimize feature transmission in the encoder, reducing semantic gaps and achieving accurate liver segmentation. To validate the effectiveness of the algorithm, experiments were conducted on the LiTS dataset. The results showed that the Dice coefficient and HD95 index for liver images were 92.56% and 28.09 mm, respectively, representing an improvement of 0.84% and a reduction of 2.45 mm compared to 3D Res-UNet.

Carcinogenic health outcomes associated with endocrine disrupting chemicals exposure in humans: A wide-scope analysis.

Endocrine-disrupting chemicals (EDCs) are persistent and pervasive compounds that pose serious risks. Numerous studies have explored the effects of EDCs on human health, among which tumors have been the primary focus. However, because of study design flaws, lack of effective exposure levels of EDCs, and inconsistent population data and findings, it is challenging to draw clear conclusions on the effect of these compounds on tumor-related outcomes. Our study is the first to systematically integrate observational studies and randomized controlled trials from over 20 years and summarize over 300 subgroup associations. We found that most EDCs promote tumor development, and that exposure to residential environmental pollutants may be a major source of pesticide exposure. Furthermore, we found that phytoestrogens exhibit antitumor effects. The findings of this study can aid in the development of global EDCs regulatory health policies and alleviate the severe risks associated with EDCs exposure.

Investigation of nutrition status and analysis of 180-day readmission factors in elderly hospitalized patients with COPD.

BACKGROUND AND OBJECTIVE: Malnutrition is prevalent among elderly patients with COPD, who also experience a high rate of readmission. Therefore, it is imperative to investigate the nutrition status of these patients, identify risk factors for readmission, and offer insights for clinical management. To achieve this, a cross-sectional study was conducted to investigate factors influencing nutrition status using GLIM criteria and explore the 180-day readmission factors among hospitalized elderly COPD patients. METHORDS AND RESULTS: The data were collected from a hospital in Southwest China, encompassing a cohort of 319 eligible patients. Among elderly hospitalized COPD patients, the prevalence of malnutrition was 49.53% (158/319). Multivariate logistic regression revealed malnutrition (OR = 3.184), very severe airway obstruction (OR = 3.735), and Number of comorbidities ≥ 3 (OR = 5.754) as significant risk factors for 180-day readmission. CONCLUSIONS: These findings suggest that malnutrition is a prevalent issue among elderly hospitalized patients with COPD and constitutes one of the risk factors contributing to the 180-day readmission rate. Therefore, timely identification and treatment for malnourished patients are crucial.

Anti-CTLA-4 m2a Antibody Exacerbates Cardiac Injury in Experimental Autoimmune Myocarditis Mice By Promoting Ccl5-Neutrophil Infiltration.

The risk for suffering immune checkpoint inhibitors (ICIs)-associated myocarditis increases in patients with pre-existing conditions and the mechanisms remain to be clarified. Spatial transcriptomics, single-cell RNA sequencing, and flow cytometry are used to decipher how anti-cytotoxic T lymphocyte antigen-4 m2a antibody (anti-CTLA-4 m2a antibody) aggravated cardiac injury in experimental autoimmune myocarditis (EAM) mice. It is found that anti-CTLA-4 m2a antibody increases cardiac fibroblast-derived C-X-C motif chemokine ligand 1 (Cxcl1), which promots neutrophil infiltration to the myocarditic zones (MZs) of EAM mice via enhanced Cxcl1-Cxcr2 chemotaxis. It is identified that the C-C motif chemokine ligand 5 (Ccl5)-neutrophil subpopulation is responsible for high activity of cytokine production, adaptive immune response, NF-κB signaling, and cellular response to interferon-gamma and that the Ccl5-neutrophil subpopulation and its-associated proinflammatory cytokines/chemokines promoted macrophage (Mφ) polarization to M1 Mφ. These altered infiltrating landscape and phenotypic switch of immune cells, and proinflammatory factors synergistically aggravated anti-CTLA-4 m2a antibody-induced cardiac injury in EAM mice. Neutralizing neutrophils, Cxcl1, and applying Cxcr2 antagonist dramatically alleviates anti-CTLA-4 m2a antibody-induced leukocyte infiltration, cardiac fibrosis, and dysfunction. It is suggested that Ccl5-neutrophil subpopulation plays a critical role in aggravating anti-CTLA-4 m2a antibody-induced cardiac injury in EAM mice. This data may provide a strategic rational for preventing/curing ICIs-associated myocarditis.

Role of natural resources, renewable energy sources, eco-innovation and carbon taxes in carbon neutrality: Evidence from G7 economies.

Global warming has created problems for human life, and it has been increasing for a few years. All the developing and developed countries are establishing policies to attain zero carbon status. This study extends the ongoing debate on carbon emissions. It examines the effect of natural resources and RE (Biofuel and other renewable sources) on greenhouse gas (CO2 emission and PM2.5) emissions while using data over 22 years (1999-2021) from G7 countries. In addition, this study has investigated the effect of carbon taxes, financial development, and environmental policies on carbon neutrality. The cross-sectional-ARDL, the Common correlated effect means group (CCEMG), and the Augmented mean group (AMG) cutting-edge model have been employed. Quantile regression has been employed for robustness. The study results demonstrate that biofuel and other renewable energy (RE) sources, carbon taxes, environmental policy, and eco-innovation decrease greenhouse gas emissions (CO2 emissions). Meanwhile, financial development, and natural resource dependence positively impact carbon neutrality. The robustness result also verifies the findings from CS-ARDL, AMG, and CCEMG methods. The empirical findings are used to infer policy implications for G7 economies.

Transperineal 3-Core Magnetic Resonance Imaging Ultrasound Fusion Targeted Plus Laterally 6-Core Systematic Biopsy in Prostate Cancer Diagnosis.

INTRODUCTION: It is important to explore strategies reducing the number of SB cores taken to minimize biopsy-related morbidity and patient's discomfort during biopsy. This study aims to optimize prostate biopsy procedures by reducing the number of systematic biopsy (SB) cores while preserving cancer detection rates in the era of combined biopsy. PATIENTS AND METHODS: We prospectively recruited patients with ≥1 magnetic resonance imaging (MRI) lesions and they underwent transperineal combined 12-core SB+3-core targeted prostate biopsy (TB, reference standard). New strategy was defined as a laterally 6-core SB+3-core TB. Patients were served as their own control. Detection rates for overall prostate cancer (PCa) and clinically significant PCa (csPCa) were compared among the standard SB, MRI-TB, 6-core SB +3-core TB, and reference standard. Pathology consistency was assessed using the Kappa test. RESULTS: A total of 204 men were included, of which 111 (54.41%) and 92 (45.10%) harbored overall PCa and csPCa. Referenced combined biopsy detected significantly 6.86% (P = .0005) or 4.90% (P = .0044) more csPCa than performing only SB or 3-core TB, but was comparable to the new biopsy strategy. (45.10% vs. 43.14%, P = .1336) Similar results persisted when limiting patients in biopsy-naïve men or stratified by Prostate Imaging Reporting and Data System scores, PSAD, and index lesion parameters. Additionally, performing 6-core SB+3-core TB demonstrated high consistency with reference standard in grade group distribution (Kappa coefficient: 0.952 for all, 0.961 for biopsy-naïve men) and achieved superior sensitivity of 95.7% (All: 95% CI: 89.2%-99.8%) and 96.9% (Biopsy-naïve: 95% CI: 91.1%-99.7%), respectively. CONCLUSIONS: The 6-core SB+3-core TB approach maintains expected detection rates while reducing the total core count, offering a promising alternative to the reference standard, which may help to tailor transperineal combined biopsy procedures.

Long-term outcomes and predictive factors of achieving low disease activity status in childhood systemic lupus erythematosus: a Chinese bicentric retrospective registered study.

Background: This study aims to explore the clinical value of low disease activity state (LDAS) in the treat-to-target strategy of pediatric systemic lupus erythematosus (pSLE) and find the risk factors for never reaching LDAS. Methods: A total of 272 children with SLE who were diagnosed and followed up in two tertiary hospitals in China during the period from January 2012 to December 2019 were involved in this study, and the clinical presentation, pathology, and treatment were retrospectively studied. Results: The male-to-female ratio was 1:5.2, the age at diagnosis was 11.1 years (IQR, 9.8-13.1 years), the disease duration was 1.0 month (IQR, 0.5-2.0 months), and follow-up was 36.5 months (IQR, 25.7-50.9 months). During follow-up, 230 children achieved LDAS, and 42 were never been in. Male (P = 0.018), mucosal ulcer (P = 0.048), liver function damage (P = 0.026), cardiac effusion (P = 0.034), anemia (P = 0.048), urine red blood cells (P = 0.017), urinary leukocytes (P = 0.032), and endothelial cell proliferation in renal biopsy (P = 0.004)-these indexes have statistical differences between the two groups in the baseline. At baseline, endothelial cell proliferation (P = 0.02) is an independent risk factor for never achieving LDAS by multivariate logistic analysis. During follow-up, non-compliance was a risk factor for never achieving LDAS by comparing between groups. Children with biologics achieved LDAS at a higher rate than children without biologics (P = 0.038). The proportion of organ damage in patients never been in LDAS was significantly higher than that in patients who achieved LDAS (P < 0.001). Conclusion: Endothelial cell proliferation in renal biopsy and non-compliance during follow-up were independent risk factors for never achieving LDAS. At the end of the follow-up, the organ damage in the remission group was similar to that in the LDAS group, indicating that LDAS can be used as a target for pSLE treatment.

Enhancing the Biological Performance of Titanium Alloy through In Situ Modulation of the Surface Nanostructure: Near-Infrared-Responsive Antibacterial Function and Osteoinductivity.

The poor clinical performance of titanium and its alloy implants is mainly attributed to their lack of antibacterial ability and poor osseointegration. The key and challenge lie in how to enhance their osteoinductivity while imparting antibacterial capability. In this study, a titanium oxide metasurface with light-responsive behavior was constructed on the surface of titanium alloy using an alkaline-acid bidirectional hydrothermal method. The effects of the acid type, acid concentration, hydrothermal time, hydrothermal temperature, and subsequent heat treatments on the optical behavior of the metasurface were systematically investigated with a focus on exploring the influence of the metasurface and photodynamic reaction on the osteogenic activity of osteoblasts. Results show that the type of acid and heat treatment significantly affect the light absorption of the titanium alloy surface, with HCl and post-heat-treatment favoring redshift in the light absorption. Under 808 nm near-infrared (NIR) irradiation for 10 min, in vitro antibacterial experiments demonstrate that the antibacterial rate of the metasurface titanium alloy against Staphylococcus aureus and Escherichia coli were 96.87% and 99.27%, respectively. In vitro cell experiments demonstrate that the nanostructure facilitates cell adhesion, proliferation, differentiation, and expression of osteogenic-related genes. Surprisingly, the nanostructure promoted the expression of relevant osteogenic genes of MC3T3-E1 under 808 nm NIR irradiation. This study provides a method for the surface modification of titanium alloy implants.

Exploring the relationships between exposure levels of bisphenols and phthalates and prostate cancer occurrence.

We established an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for simultaneously analyzing the metabolites of bisphenols and phthalates in urine to identify the associations between these exposure levels and prostate cancer (PCa) based on a case-control study. After purifying urine samples with SPE, 18 metabolites were separated on a C18 column, and MS detection was performed. The UPLC-MS/MS method has been proven effective at evaluating bisphenol and phthalate exposure (0.020-0.20 µg/L of the limits of detection, 71.8 %∼119.4 % of recoveries, 0.4 %∼8.2 % of precision). Logistic regression explored the association between exposure level and PCa in 187 PCa cases and 151 controls. The detection rates of bisphenol A (BPA) and most phthalate metabolites were 100 % ranging from 0.06-46.74 and 0.12-899.92 µg/g creatinine, respectively, while the detection rates of other bisphenols and mono-benzyl phthalate (MBzP) are low, ranging from 0 % to 21.85 %. Correlation analysis of the metabolite levels indicated that the exposure sources of BPA, di-ethyl phthalate (DEP), and di(2-ethylhexyl) phthalate (DEHP) were different, and that the exposure sources of di-n-butyl phthalate (DnBP) and di-isobutyl phthalate (DiBP) may differ between two groups. Logistic regression analysis revealed that BPA (OR<0.45 vs ≥1.43 =10.02) and DEHP exposure (OR<21.75 vs ≥45.42 =48.26) increased the risk of PCa.

Preoperative N-terminal Pro-B-type Natriuretic Peptide and High-sensitivity Cardiac Troponin T and Outcomes after Major Noncardiac Surgery: A Prospective Cohort Study.

BACKGROUND: Patients undergoing noncardiac surgery have varying risk of cardiovascular complications. This study evaluated preoperative N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T to enhance cardiovascular events prediction for major noncardiac surgery. METHODS: This prospective cohort study included adult patients with cardiovascular disease or risk factors undergoing elective major noncardiac surgery at four hospitals in China. Blood samples were collected within 30 days before surgery for NT-proBNP and high-sensitivity troponin T (hs-TnT) measurements. The primary outcome was a composite of any cardiovascular events within 30 days after surgery. Logistic regression models were used to assess associations, and the predictive performance was evaluated primarily using area under the receiver operating characteristics curve (AUC) and fraction of new predictive information. RESULTS: Between June 2019 and September 2021, a total of 2,833 patients were included, with 435 (15.4%) experiencing the primary outcome. In the logistic regression model that included clinical variables and both biomarkers, the odds ratio for the primary outcome was 1.68 (95% CI, 1.37 to 2.07) when comparing the 75th percentile to the 25th percentile of NT-proBNP distribution, and 1.91 (95% CI, 1.50 to 2.43) for hs-TnT. Each biomarker enhanced model discrimination beyond clinical predictors, with a change in AUC of 0.028 for NT-proBNP and 0.029 for high-sensitivity cardiac troponin T, and a fraction of new information of 0.164 and 0.149, respectively. The model combining both biomarkers demonstrated the best discrimination, with a change in AUC of 0.042 and a fraction of new information of 0.219. CONCLUSIONS: Preoperative NT-proBNP and hs-TnT both improved the prediction for cardiovascular events after noncardiac surgery in addition to clinical evaluation, with their combination providing maximal predictive information.

Trends in the global, regional, and national burden of testicular cancer from 1990 to 2019: an observational study with 30-year global data.

BACKGROUND: Testicular cancer (TC) is currently the most common malignancy in young and middle-aged men. A comprehensive assessment of TC burden is in lack. METHOD: Global incidence, deaths, and disability-adjusted life-years (DALYs) of TC from 1990 to 2019 were obtained. Estimated annual percentage change (EAPC) was calculated to quantify trends in TC changes during the period. Relationships between disease burden and age, socio-demographic index (SDI) levels, human development index (HDI) were further analyzed. RESULTS: Globally, incident cases of TC more than doubled from 1990 to 2019, together with an increasing of global age-standardized incidence rates (ASIR) of TC from 1.9 to 2.8. The age-standardized deaths rates (ASDR) remained stable from 0.31 to 0.28. The similar results were reflected in the DALYs. In 2019, the highest ASIR were found in Southern Latin America, Central Europe and Western Europe. Analogously, the highest ASDR were found in Southern Latin America followed by Central Latin America and Central Europe. The burden of incidence increased with SDI, appropriately reached a peak at about 0.78, and then declined. Similarly, the burden of deaths increased with SDI, met a maximum at about 0.7. CONCLUSIONS: From 1990 to 2019, the ASIR of TC has increased significantly, while the ASDR has been relatively stable and slightly decreased. The disease burden of TC is shifting to regions and countries with moderate to high levels of development. TC remains a rapidly growing global health problem, and new changes in TC burden should be considered when formulating new TC control policies.

Metabolomics for Clinical Biomarker Discovery and Therapeutic Target Identification.

As links between genotype and phenotype, small-molecule metabolites are attractive biomarkers for disease diagnosis, prognosis, classification, drug screening and treatment, insight into understanding disease pathology and identifying potential targets. Metabolomics technology is crucial for discovering targets of small-molecule metabolites involved in disease phenotype. Mass spectrometry-based metabolomics has implemented in applications in various fields including target discovery, explanation of disease mechanisms and compound screening. It is used to analyze the physiological or pathological states of the organism by investigating the changes in endogenous small-molecule metabolites and associated metabolism from complex metabolic pathways in biological samples. The present review provides a critical update of high-throughput functional metabolomics techniques and diverse applications, and recommends the use of mass spectrometry-based metabolomics for discovering small-molecule metabolite signatures that provide valuable insights into metabolic targets. We also recommend using mass spectrometry-based metabolomics as a powerful tool for identifying and understanding metabolic patterns, metabolic targets and for efficacy evaluation of herbal medicine.

Diabetes and aortic dissection: unraveling the role of 3-hydroxybutyrate through mendelian randomization.

BACKGROUND: In observational and experimental studies, diabetes has been reported as a protective factor for aortic dissection. 3-Hydroxybutyrate, a key constituent of ketone bodies, has been found to favor improvements in cardiovascular disease. However, whether the protective effect of diabetes on aortic dissection is mediated by 3-hydroxybutyrate is unclear. We aimed to investigate the causal effects of diabetes on the risk of aortic dissection and the mediating role of 3-hydroxybutyrate in them through two-step Mendelian randomization. MATERIALS AND METHODS: We performed a two-step Mendelian randomization to investigate the causal connections between diabetes, 3-hydroxybutyrate, and aortic dissection and calculate the mediating effect of 3-hydroxybutyrate. Publicly accessible data for Type 1 diabetes, Type 2 diabetes, dissection of aorta and 3-hydroxybutyrate were obtained from genome-wide association studies. The association between Type 1 diabetes and dissection of aorta, the association between Type 2 diabetes and dissection of aorta, and mediation effect of 3-hydroxybutyrate were carried out separately. RESULTS: The IVW method showed that Type 1 diabetes was negatively associated with the risk of aortic dissection (OR 0.912, 95% CI 0.836-0.995), The weighted median, simple mode and weighted mode method showed consistent results. The mediated proportion of 3-hydroxybutyrate on the relationship between Type 1 diabetes and dissection of aorta was 24.80% (95% CI 5.12-44.47%). The IVW method showed that Type 2 diabetes was negatively associated with the risk of aortic dissection (OR 0.763, 95% CI 0.607-0.960), The weighted median, simple mode and weighted mode method showed consistent results. 3-Hydroxybutyrate does not have causal mediation effect on the relationship between Type 2 diabetes and dissection of aorta. CONCLUSION: Mendelian randomization study revealed diabetes as a protective factor for dissection of aorta. The protective effect of type 1 diabetes on aortic dissection was partially mediated by 3-hydroxybutyrate, but type 2 diabetes was not 3-hydroxybutyrate mediated.

Endoscopic papillectomy for synchronous adenoma of the major and minor duodenal papilla.

OBJECTIVES: Synchronous adenomas of the major and minor duodenal papilla are seldom reported. The aim of this study was to describe the characteristics of synchronous major and minor papilla adenomas and to evaluate the safety and efficacy of endoscopic papillectomy (EP) for the management of the disease. METHODS: Consecutive patients who underwent endoscopy for synchronous major and minor papilla adenomas from January 1, 2013 to August 31, 2023 were analyzed retrospectively. Patients' characteristics, clinical manifestations, laboratory, imaging and endoscopic findings were collected. RESULTS: The nine patients with synchronous major and minor papilla adenomas had an average age of 50.78 ± 10.70 years. The diameter of major and minor papilla adenomas was 12.11 ± 3.41 mm and 6.11 ± 1.05 mm, respectively. Most major papilla adenomas had R0 horizontal margins (n = 8), while R0 vertical margins were achieved in all patients. While minor papilla adenomas were resected with both R0 horizontal and vertical margins in all patients. Post-EP bleeding was observed in one patient, which was classified as mild. Post-EP hyperamylasemia and pancreatitis was observed in two and four patients, respectively; the latter consisted of three with mild pancreatitis and one with severe pancreatitis. No perforation was observed. The mean follow-up duration was 9.22 ± 5.99 months. Histologically confirmed recurrence at the resection site was detected in one patient at 3 months after the procedure. CONCLUSIONS: Synchronous major and minor papilla adenomas may not be as rare as previously speculated. EP may be an effective and safe alternative modality for their management.