Plasma Deoxycholic Acid Levels are Associated with Hemodynamic and Clinical Outcomes in Acute Pulmonary Embolism Patients.

This study aimed to evaluate the correlation of plasma deoxycholic acid (DCA) levels with clinical and hemodynamic parameters in acute pulmonary embolism (APE) patients. Total 149 APE adult patients were prospectively recruited. Plasma DCA levels were measured using rapid resolution liquid chromatography-quadrupole time-of-flight mass spectrometry. Baseline clinical and hemodynamic parameters were evaluated according to plasma DCA levels. The plasma DCA levels were significantly lower in APE patients than in those without APE (P < 0.001). APE patients with adverse events had lower plasma DCA levels (P < 0.001). Low DCA group patients presented more adverse cardiac function, higher NT-proBNP levels (P = 0.010), and higher WHO functional class levels (P = 0.023). Low DCA group also presented with an adverse hemodynamic status, with higher pulmonary vascular resistance levels (P = 0.027) and lower cardiac index levels (P = 0.024). Both cardiac function and hemodynamic parameters correlated well with plasma DCA levels. Kaplan-Meier survival analysis demonstrated that APE patients with lower plasma DCA levels had a significantly higher event rate (P = 0.009). In the univariate and multivariate Cox regression analyses, the plasma DCA level was an independent predictor of clinical worsening events after adjusting for age, sex, WHO functional class, NT-proBNP level, pulmonary vascular resistance, and cardiac index (HR 0.370, 95% CI 0.161, 0.852; P = 0.019). Low plasma DCA levels predicted adverse cardiac function and hemodynamic collapse. A low DCA level was correlated with a higher clinical worsening event rate and could be an independent predictor of clinical outcomes in multivariate analysis.

Blood mercury mediates the associations between fish consumption and serum uric acid levels among Chinese adults: A nationally representative study.

Fish consumption can increase purine load in human body, and the enrichment of mercury in fish may affect the glomerular filtration function, both resulting in increased serum uric acid (SUA) levels. The data of blood mercury (BHg), fish consumption frequency and SUA levels of 7,653 participants aged 18 years or older was from China National Human Biomonitoring (2017-2018). The relationships between fish consumption frequency, ln-transformed BHg and SUA levels were explored through weighted multiple linear regressions. The mediating effect of BHg levels between fish consumption frequency and SUA levels was evaluated by mediation analysis. We found that both the fish consumption frequency and BHg were positively associated with SUA levels in both sexes. Compared to participants who had never consumed fish, participants who consumed fish once a week or more had higher SUA levels [ß (95% confidence interval, CI): 20.39 (2.16, 38.62) in males; ß (95% CI): 10.06 (0.76, 19.37) in females] and ln-transformed BHg [ß (95% CI): 0.97 (0.61, 1.34) in males; ß (95% CI): 0.84 (0.63, 1.05) in females]. Each 1-unit increase in ln-transformed BHg, the SUA levels rose by 4.78 (95% CI: 0.01, 9.54) µmol/L for males and 3.81 (95% CI: 1.60, 6.03) µmol/L for females. The relation between fish consumption with SUA levels was mediated by ln-transformed BHg with the percent mediated of 34.66% in males and 26.58% in females. It revealed that BHg played mediating roles in the elevation of SUA levels caused by fish consumption. This study's findings could promote the government to intervene in mercury pollution in fish, so as to ensure the safety of fish consumption.

Feasibility experimental study on plugging leakage in goaf based on two-phase foam.

Air leakage in goaf often leads to coal spontaneous combustion (CSC), which not only directly affects the safety production of mines but also causes significant environmental damage. Therefore, effectively sealing the airflow in goaf is crucial for preventing CSC. Feasibility experiments on using two-phase foam to seal air leakage in goaf were conducted, leveraging the advantages of large flow rate, wide diffusion range, and good accumulation characteristics of two-phase foam. The research results indicate that continuous injection of foam into loose media with maintained ventilation can completely seal the air leakage, with the foam capable of withstanding wind pressures of nearly 600 Pa. When the foam is used for one-time sealing with a length of 2 m, it remains effective for 60 min, and the sealing effectiveness improves with longer distances sealed against air leakage. Numerical simulation analysis and field measurements of airflow leakage in mine working faces reveal that effectively sealing the airflow passage in the goaf behind the corner of the return airway is crucial for preventing CSC. Two methods are proposed for sealing external airflow during coal mining: foam injection using a point drilling method near the heading and an incremental buried pipe injection method. Finally, the feasibility of two-phase foam sealing technology for goaf airflow leakage is analyzed from multiple perspectives including sealing effectiveness, practicality, economy, foaming process, and engineering implementation. The research findings provide new insights into goaf sealing technology, aiding in addressing safety and environmental issues caused by spontaneous combustion in goaf areas.

Association between non-alcoholic fatty liver disease and the risk of pulmonary nodules in patients with intestinal polyps.

Background: Associations between metabolic risk factors and lung cancer remain elusive, and evidence on the linkage between non-alcoholic fatty liver disease (NAFLD) and pulmonary nodules is limited. This study sought to examine the independent association between NAFLD and the risk of pulmonary nodules. Methods: Cross-sectional analyses of 1,119 patients with intestinal polyps hospitalized at the Department of Gastroenterology, Minhang District Central Hospital of Shanghai, China, were conducted. NAFLD was diagnosed based on hepatic ultrasonography or computed tomography (CT) findings of hepatic steatosis, with exclusion criteria ensuring patients had no history of significant alcohol consumption, viral infections, or hepatic autoimmune diseases. The currently accepted definition of a pulmonary nodule is a solid or sub-solid shadow ≤3 cm in diameter that appears as a solid or semi-solid pattern on a chest CT scan (our specific treatment is pulmonary nodule size: 5 mm to 3 cm). Adjusted 95% confidence intervals (CIs) and odds ratios (ORs) for NAFLD and the clinical features connected with pulmonary nodule risk were determined using a multivariable logistic regression analysis. Results: Among the 979 intestinal polyp patients, the prevalence rates of NAFLD and pulmonary nodules were 25.9% and 32.8%, respectively. Patients with pulmonary nodules exhibited higher rates of NAFLD (31.5% vs. 23.3%, P=0.006) and obesity (41.4% vs. 32.5%, P=0.006) compared to those without pulmonary nodules. After removing all the possible confounding variables, the adjusted ORs for NAFLD, an older age, smoking, and obesity were 1.370 (95% CI: 1.006-1.867, P=0.04), 1.022 (95% CI: 1.010-1.033), 1.599 (95% CI: 1.033-2.475), and 1.410 (95% CI: 1.057-1.880), respectively (all P values <0.05). NAFLD showed a significant association with an increased risk of pulmonary nodules. Conclusions: NAFLD was independently linked to an increased incidence of pulmonary nodules in intestinal polyp patients, which emphasizes the importance of screening and managing these conditions in lung cancer prevention.

Integrating gravity-driven ceramic membrane filtration with hydroponic system for nutrient recovery from primary municipal wastewater.

In this study, a gravity-driven membrane (GDM) filtration system and hydroponic system (cultivating basil and lettuce) were combined for nutrient recovery from primary municipal wastewater. The GDM system was optimized by increasing the periodic air sparging flow rate from 1 to 2 L/min (∼15 hr per 3-4 days), resulting in a ∼52% reduction of irreversible fouling. However, the total fouling was not alleviated, and the water productivity remained comparable. The GDM-filtrated water was then delivered to hydroponic systems, and the effects of hydroponic operation conditions on plant growth and heavy metal uptake were evaluated, with fertilizer- and tap water-based hydroponic systems and soil cultivation system (with tap water) for comparison. It was found that (i) the hydroponic system under batch mode facilitated to promote vegetable growth with higher nutrient uptake rates compared to that under flow-through feed mode; (ii) a shift in nutrient levels in the hydroponic system could impact plant growth (such as plant height and leaf length), especially in the early stages. Nevertheless, the plants cultivated with the GDM-treated water had comparable growth profiles to those with commercial fertilizer or in soils. Furthermore, the targeted hazard quotient levels of all heavy metals for the plants in the hydroponic system with the treated water were greatly lower than those with the commercial fertilizer. Especially, compared to the lettuce, the basil had a lower heavy metal uptake capability and displayed a negligible impact on long-term human health risk, when the treated water was employed for the hydroponic system.

Imbalance of mitochondrial quality control regulated by STING and PINK1 affects cyfluthrin-induced neuroinflammation.

Nervous system diseases are a global health problem, and with the increase in the elderly population around the world, their incidence will also increase. Harmful substances in the environment are closely related to the occurrence of nervous system diseases. China is a large agricultural country, and thus the insecticide cyfluthrin has been widely used. Cyfluthrin is neurotoxic, but the mechanism of this injury is not clear. Inflammation is an important mechanism for the occurrence of nervous system diseases. Mitochondria are the main regulators of the inflammatory response, and various cellular responses, including autophagy, directly affect the regulation of inflammatory processes. Mitochondrial damage is related to mitochondrial quality control (MQC) and PTEN-induced kinase 1 (PINK1). As an anti-inflammatory factor, stimulator of interferon genes (STING) participates in the regulation of inflammation. However, the relationship between STING and mitochondria in the process of cyfluthrin-induced nerve injury is unclear. This study established in vivo and in vitro models of cyfluthrin exposure to explore the role of MQC and to clarify the mechanism of action of STING and PINK1. Our results showed that cyfluthrin can increase the reactive oxygen species (ROS) level, resulting in mitochondrial damage and inflammation. In this process, an imbalance in MQC leads to the aggravation of mitochondrial damage, and high STING expression drives the occurrence of inflammation. We established a differential expression model of STING and PINK1 to further determine the underlying mechanism and found that the interaction between STING and PINK1 regulates MQC to affect the levels of mitochondrial damage and inflammation. When STING and PINK1 expression are downregulated, mitochondrial damage and STING-induced inflammation are significantly alleviated. In summary, a synergistic effect between STING and PINK1 on cyfluthrin-induced neuroinflammation may exist, which leads to an imbalance in MQC by inhibiting mitochondrial biogenesis and division/fusion, and PINK1 can reduce STING-driven inflammation.

A Real-Time Contact-Free Atrial Fibrillation Detection System for Mobile Devices.

As the global population ages, the death and prevalence of atrial fibrillation (AF) continue to rise, posing significant concerns due to its strong association with stroke-related disabilities. Detecting AF early before a stroke occurs has become paramount. However, existing methods face challenges in achieving quick, easy, and affordable detection in complex environments characterized by motion interference and varying light conditions. To address these challenges, we propose a system that is employable for edge computing devices like smartphones, tablets, or laptops. Meanwhile, to ensure that the dataset reflects real-world scenarios, we collect 7,216 30-second segments from 452 subjects, categorized into Atrial Fibrillation (AF), Normal Sinus Rhythm (NSR), and Other Arrhythmias (Others), with a subject ratio of 105:116:231. Our lightweight non-contact facial rPPG atrial fibrillation detection system utilizes a Convolution Neural Network (CNN) with a large receptive field and a bidirectional spatial mapping augmented attention module (BiSME-ATT) coupled with a bidirectional feature pyramid network layer (BiFPN), optimized for deployment on mobile devices by reducing model parameters and floating-point operations per second (FLOPs). Our approach significantly improves AF detection accuracy, sensitivity, specificity, positive predictive value, and negative predictive value to 94.39%, 91.57%, 95.44%, 88.06%, and 96.93%, respectively, in AF vs. Non-AF scenarios. Furthermore, the results demonstrate notable enhancements in AF detection across various motion and light intensity levels.

Fabric structure and polymer composition as key contributors to micro(nano)plastic contamination in face masks.

The surge in face mask use due to COVID-19 has raised concerns about micro(nano)plastics (MNPs) from masks. Herein, focusing on fabric structure and polymer composition, we investigated MNP generation characteristics, mechanisms, and potential risks of surgical polypropylene (PP) and fashionable polyurethane (PU) masks during their wearing and photoaging based on stereomicroscope, µ-Fourier transform infrared spectroscopy (µ-FTIR), and scanning electron microscope (SEM) techniques. Compared with new PP and PU masks (66 ± 16 MPs/PP-mask, 163 ± 83 MPs/PU-mask), single- and multiple-used masks exhibited remarkably increased MP type and abundance (600-1867 MPs/PP-mask, 607-2167 MPs/PU-mask). Disinfection exacerbated endogenous MP generation in masks, with washing (416 MPs/PP-mask, 30,708 MPs/PU-mask) being the most prominent compared to autoclaving (219 MPs/PP-mask, 553 MPs/PU-mask) and alcohol spray (162 MPs/PP-mask, 18,333 MPs/PU-mask). Photoaging led to massive generation of MPs (8.8 × 104-3.7 × 105 MPs/PP-layer, 1.0 × 105 MPs/PU-layer) and NPs (5.2 × 109-3.6 × 1013 NPs/PP-layer, 3.5 × 1012 NPs/PU-layer) from masks, presenting highly fabric structure-dependent aging modes as "fragmentation" for fine fiber-structure PP mask and "erosion" for 3D mesh-structure PU mask. The MNPs derived from PP/PU mask caused significant deformities of Zebrafish (Danio rerio) larvae. These findings underscore the potential adverse effects of masks on humans and aquatic organisms, advocating to enhance proper use and rational disposal for masks.

Lomitapide repurposing for treatment of malignancies: A promising direction.

The development of novel drugs from basic science to clinical practice requires several years, much effort, and cost. Drug repurposing can promote the utilization of clinical drugs in cancer therapy. Recent studies have shown the potential effects of lomitapide on treating malignancies, which is currently used for the treatment of familial hypercholesterolemia. We systematically review possible functions and mechanisms of lomitapide as an anti-tumor compound, regarding the aspects of apoptosis, autophagy, and metabolism of tumor cells, to support repurposing lomitapide for the clinical treatment of tumors.

Associations of Serum Per- and Polyfluoroalkyl Substances with Hyperuricemia in Adults: A Nationwide Cross-Sectional Study.

There has been widespread concern about the health hazards of per- and polyfluoroalkyl substances (PFAS), which may be the risk factor for hyperuricemia with evidence still insufficient in the general population in China. Here, we conducted a nationwide study involving 9,580 adults aged 18 years or older from 2017 to 2018, measured serum concentrations of uric acid and PFAS (PFOA, PFOS, 6:2 Cl-PFESA, PFNA, PFHxS) in participants, to assess the associations of individual PFAS with hyperuricemia, and estimated a joint effect of PFAS mixtures. We found positive associations of higher serum PFAS with elevated odds of hyperuricemia in Chinese adults, with the greatest contribution from PFOA (69.37%). The nonmonotonic dose-response (NMDR) relationships were observed for 6:2 Cl-PFESA and PFHxS with hyperuricemia. Participants with less marine fish consumption, overweight, and obesity may be the sensitive groups to the effects of PFAS on hyperuricemia. We highlight the potential health hazards of legacy long-chain PFAS (PFOA) once again because of the higher weights of joint effects. This study also provides more evidence about the NMDR relationships in PFAS with hyperuricemia and emphasizes a theoretical basis for public health planning to reduce the health hazards of PFAS in sensitive groups.

Machine learning predicts the serum PFOA and PFOS levels in pregnant women: Enhancement of fatty acid status on model performance.

Human exposure to per- and polyfluoroalkyl substances (PFASs) has received considerable attention, particularly in pregnant women because of their dramatic changes in physiological status and dietary patterns. Predicting internal PFAS exposure in pregnant women, based on external and relevant parameters, has not been investigated. Here, machine learning (ML) models were developed to predict the serum concentrations of PFOA and PFOS in a large population of 588 pregnant participants. Dietary exposure characteristics, demographic parameters, and in particular, serum fatty acid (FA) data were used for the model development. The fitting results showed that the inclusion of FAs as covariates significantly improved the performance of the ML models, with the random forest (RF) model having the best predictive performance for PFOA (R2 = 0.33, MAE = 1.51 ng/mL, and RMSE = 1.89 ng/mL) and PFOS (R2 = 0.12, MAE = 2.65 ng/mL, and RMSE = 3.37 ng/mL). The feature importance analysis revealed that serum FAs greatly affected PFOA concentration in the pregnant women, with saturated FAs being associated with decreased PFOA levels and unsaturated FAs with increased levels. Comparison with one-compartment pharmacokinetic model further demonstrated the advantage of the ML models in predicting PFAS exposure in pregnant women. Our models correlate for the first time blood chemical concentrations with human FA status using ML, introducing a novel perspective on predicting PFAS levels in pregnant women. This study provides valuable insights concerning internal exposure of PFASs generated from external exposure, and contributes to risk assessment and management in pregnant populations.

Engineered Exosomes Containing microRNA-29b-2 and Targeting the Somatostatin Receptor Reduce Presenilin 1 Expression and Decrease the ß-Amyloid Accumulation in the Brains of Mice with Alzheimer's Disease.

Purpose: Exosomes are membrane vesicles secreted by various cells and play a crucial role in intercellular communication. They can be excellent delivery vehicles for oligonucleotide drugs, such as microRNAs, due to their high biocompatibility. MicroRNAs have been shown to be more stable when incorporated into exosomes; however, the lack of targeting and immune evasion is still the obstacle to the use of these microRNA-containing nanocarriers in clinical settings. Our goal was to produce functional exosomes loaded with target ligands, immune evasion ligand, and oligonucleotide drug through genetic engineering in order to achieve more precise medical effects. Methods: To address the problem, we designed engineered exosomes with exogenous cholecystokinin (CCK) or somatostatin (SST) as the targeting ligand to direct the exosomes to the brain, as well as transduced CD47 proteins to reduce the elimination or phagocytosis of the targeted exosomes. MicroRNA-29b-2 was the tested oligonucleotide drug for delivery because our previous research showed that this type of microRNA was capable of reducing presenilin 1 (PSEN1) gene expression and decreasing the ß-amyloid accumulation for Alzheimer's disease (AD) in vitro and in vivo. Results: The engineered exosomes, containing miR29b-2 and expressing SST and CD47, were produced by gene-modified dendritic cells and used in the subsequent experiments. In comparison with CD47-CCK exosomes, CD47-SST exosomes showed a more significant increase in delivery efficiency. In addition, CD47-SST exosomes led to a higher delivery level of exosomes to the brains of nude mice when administered intravenously. Moreover, it was found that the miR29b-2-loaded CD47-SST exosomes could effectively reduce PSEN1 in translational levels, which resulted in an inhibition of beta-amyloid oligomers production both in the cell model and in the 3xTg-AD animal model. Conclusion: Our results demonstrated the feasibility of the designed engineered exosomes. The application of this exosomal nanocarrier platform can be extended to the delivery of other oligonucleotide drugs to specific tissues for the treatment of diseases while evading the immune system.

Positive Associations of Perfluoroalkyl and Polyfluoroalkyl Substances With Hypertension May Be Attenuated by Endogenous Sex Hormones: A Nationally Representative Cross-Sectional Study.

BACKGROUND: Perfluoroalkyl and polyfluoroalkyl substance (PFAS) has endocrine-disrupting properties and may affect blood pressure. Endogenous hormones also play a crucial role in the progression of hypertension. However, their interaction with hypertension remains to be explored. METHODS: This study included 10 794 adults aged ≥18 years from the China National Human Biomonitoring program. Weighted multiple logistic regression and linear regression were used to examine the associations of serum PFAS with hypertension, diastolic blood pressure, and systolic blood pressure. Joint effects of PFAS mixtures on hypertension, diastolic blood pressure, and systolic blood pressure were evaluated using quantile-based g-computation. Additive and multiplicative interactions were used to assess the role of PFAS with testosterone and estradiol on hypertension. RESULTS: The prevalence of hypertension in Chinese adults was 35.50%. Comparing the fourth quartile with the first quartile, odds ratio (95% CI) of hypertension were 1.53 (1.13-2.09) for perfluorononanoic acid, 1.40 (1.03-1.91) for perfluorodecanoic acid, 1.34 (1.02-1.78) for perfluoroheptane sulfonic acid, and 1.46 (1.07-1.99) for perfluorooctane sulfonic acid. Moreover, PFAS mixtures, with perfluorononanoic acid contributing the most, were positively associated with hypertension, diastolic blood pressure, and systolic blood pressure. PFAS and endogenous hormones had an antagonistic interaction in hypertension. For example, the relative excess risk ratio, attributable proportion, and synergy index for perfluorononanoic acid and estradiol were -3.61 (-4.68 to -2.53), -1.65 (-2.59 to -0.71), and 0.25 (0.13-0.47), respectively. CONCLUSIONS: Perfluorononanoic acid, perfluorodecanoic acid, perfluoroheptane sulfonic acid, perfluorooctane sulfonic acid, and PFAS mixtures showed positive associations with hypertension, systolic blood pressure, and diastolic blood pressure. Positive associations of PFAS with hypertension might be attenuated by increased levels of endogenous sex hormones.

Mitochondria fission accentuates oxidative stress in hyperglycemia-induced H9c2 cardiomyoblasts in vitro by regulating fatty acid oxidation.

Oxidative stress plays a pivotal role in the development of diabetic cardiomyopathy (DCM). Previous studies have revealed that inhibition of mitochondrial fission suppressed oxidative stress and alleviated mitochondrial dysfunction and cardiac dysfunction in diabetic mice. However, no research has confirmed whether mitochondria fission accentuates hyperglycemia-induced cardiomyoblast oxidative stress through regulating fatty acid oxidation (FAO). We used H9c2 cardiomyoblasts exposed to high glucose (HG) 33 mM to simulate DCM in vitro. Excessive mitochondrial fission, poor cell viability, and lipid accumulation were observed in hyperglycemia-induced H9c2 cardiomyoblasts. Also, the cells were led to oxidative stress injury, lower adenosine triphosphate (ATP) levels, and apoptosis. Dynamin-related protein 1 (Drp1) short interfering RNA (siRNA) decreased targeted marker expression, inhibited mitochondrial fragmentation and lipid accumulation, suppressed oxidative stress, reduced cardiomyoblast apoptosis, and improved cell viability and ATP levels in HG-exposed H9c2 cardiomyoblasts, but not in carnitine palmitoyltransferase 1 (CPT1) inhibitor etomoxir treatment cells. We also found subcellular localization of CPT1 on the mitochondrial membrane, FAO, and levels of nicotinamide adenine dinucleotide phosphate (NADPH) were suppressed after exposure to HG treatment, whereas Drp1 siRNA normalized mitochondrial CPT1, FAO, and NADPH. However, the blockade of FAO with etomoxir abolished the above effects of Drp1 siRNA in hyperglycemia-induced H9c2 cardiomyoblasts. The preservation of mitochondrial function through the Drp1/CPT1/FAO pathway is the potential mechanism of inhibited mitochondria fission in attenuating oxidative stress injury of hyperglycemia-induced H9c2 cardiomyoblasts.

A Prospective Cohort Study of Antimony Exposure and Cognitive Impairment in Older Adults - China, 2017-2021.

What is already known about this topic?: Antimony (Sb) has been identified as a new neurotoxicant that impacts neurological functions in animal studies. However, its effects on the human population remain unknown. What is added by this report?: The study reveals that there is an association between exposure to Sb and a higher incidence of cognitive impairment in older adults. The dose-response curve demonstrates that the risk of cognitive impairment consistently increased with higher levels of Sb exposure without a discernible threshold. What are the implications for public health practice?: Reducing exposure to Sb may have a beneficial effect in delaying or preventing the onset of cognitive impairment. This intervention has the potential to significantly decrease the disease burden associated with cognitive impairment, ultimately contributing to social development.

Multimodal data-driven, vertical visualization prediction model for early prediction of atherosclerotic cardiovascular disease in patients with new-onset hypertension.

BACKGROUND: : Hypertension is an important contributing factor to atherosclerotic cardiovascular disease (ASCVD), and multiple risk factors, many of which are implicated in metabolic disorders, contribute to the cause of hypertension. Despite the promise of multimodal data-driven prediction model, no such prediction model was available to predict the risk of ASCVD in Chinese individuals with new-onset hypertension and no history of ASCVD. METHODS: : A total of 514 patients were randomly allocated to training and verification cohorts (ratio, 7 : 3). We employed Boruta feature selection and conducted multivariate Cox regression analyses to identify variables associated with ASCVD in these patients, which were subsequently utilized for constructing the predictive model. The performance of prediction model was assessed in terms of discriminatory power (C-index), calibration (calibration curves), and clinical utility [decision curve analysis (DCA)]. RESULTS: : This model was derived from four clinical variables: 24-h SBP coefficient of variation, 24-h DBP coefficient of variation, urea nitrogen and the triglyceride-glucose (TyG) index. Bootstrapping with 500 iterations was conducted to adjust the C-indexes were C-index = 0.731, 95% confidence interval (CI) 0.620-0.794 and C-index: 0.799, 95% CI 0.677-0.892 in the training and verification cohorts, respectively. Calibration plots with 500 bootstrapping iterations exhibited a strong correlation between the predicted and observed occurrences of ASCVD in both the training and verification cohorts. DCA analysis confirmed the clinical utility of this prediction model. The constructed nomogram demonstrated significant additional prognostic utility for ASCVD, as evidenced by improvements in the C-index, net reclassification improvement, integrated discrimination improvement, and DCA compared with the overall ASCVD risk assessment. CONCLUSION: The developed longitudinal prediction model based on multimodal data can effectively predict ASCVD risk in individuals with an initial diagnosis of hypertension. TRIAL REGISTRATION: : The trial was registered in the Chinese Clinical Trial Registry (ChiCTR2300074392).

Structural Insights into the Mechanisms Underlying Polyaminopathies.

Polyamines are ubiquitous in almost all biological entities and involved in various crucial physiological processes. They are also closely associated with the onset and progression of many diseases. Polyaminopathies are a group of rare genetic disorders caused by alterations in the function of proteins within the polyamine metabolism network. Although the identified polyaminopathies are all rare diseases at present, they are genetically heritable, rendering high risks not only to the carriers but also to their descendants. Meanwhile, more polyaminopathic patients might be discovered with the increasing accessibility of gene sequencing. This review aims to provide a comprehensive overview of the structural variations of mutated proteins in current polyaminopathies, in addition to their causative genes, types of mutations, clinical symptoms, and therapeutic approaches. We focus on analyzing how alterations in protein structure lead to protein dysfunction, thereby facilitating the onset of diseases. We hope this review will offer valuable insights and references for the future clinical diagnosis and precision treatment of polyaminopathies.

[Mid-term effectiveness of LU-tarjet procedure for recurrent anterior shoulder dislocation].

Objective: To evaluate the mid-term effectiveness of limited unique coracoid osteotomy suture button fixation Latarjet (LU-tarjet) procedure in treatment of recurrent anterior shoulder dislocation. Methods: Between March 2017 and February 2019, 56 patients with recurrent shoulder dislocation were treated with arthroscopic LU-tarjet procedure. There were 44 males and 12 females with an average age of 26.3 years (range, 18-41 years). Shoulder joint dislocation occurred 2-16 times, with an average of 7.5 times. The time from the initial dislocation to operation ranged from 6 months to 13 years, with a median of 4.6 years. Preoperative shoulder joint fear test and re-reduction test were positive in all patients. The Beighton score of joint relaxation ranged from 1 to 7, with an average of 4.1. The shoulder Instability Severity Index Score (ISIS) ranged from 5 to 10, with an average of 7.8. The size of glenoid defects on the affected side ranged from 15% to 32% (mean, 22.4%). All patients had Hill-Sachs injuries of varying degrees. Six patients had re-dislocation after Bankart surgery. The operation time, incision healing, and postoperative complications were recorded. The range of motion (shoulder flexion, extension, abduction, external rotation, 90° external rotation, and internal rotation) and muscle strength in shoulder flexion, abduction, external rotation, and internal rotation) of shoulder joint were compared between pre- and post-operation. The improvement of shoulder function was evaluated using the American Association for Shoulder and Elbow Surgery (ASES) score, Walch-Duplay score, and Rowe score. X-ray films and three-dimensional CT were used to analyze the location, healing, and remolding of bone graft, the repair of glenoid defect, and degenerative changes of the shoulder joint. Results: All operations were successfully completed. The operation time ranged from 42 to 98 minutes, with an average of 63 minutes. All incisions healed by first intention. All patients were followed up 5-7 years (mean, 6.3 years). During follow-up, 2 patients experienced shoulder subluxation within 1 year after operation and 1 patient experienced recurrent shoulder joint pain. The remaining patients had no related complications. At last follow-up, there was no significant difference between the two groups ( P>0.05) in range of motion (shoulder flexion, extension, abduction, external rotation, 90° external rotation, and internal rotation) and muscle strength in shoulder flexion, abduction, external rotation, and internal rotation). The ASES score, Rowe score, and Walch-Duplay score of shoulder significantly improved when compared with those before operation ( P<0.05). Postoperative CT showed that 53 cases (94.64%) of coracoid bone masses were centered placed vertically, 2 cases (3.57%) were superior, and 1 case (1.79%) was inferior; 49 cases (87.50%) of the coracoid bone grafts were flush with the glenoid, 2 cases (3.57%) and 5 cases (8.93%) were medially and laterally positioned. The volume of coracoid bone graft decreased first and then increased, and the shape of the bone graft was continuously remodeling and gradually matched with the track of the humerus head (the optimal circle of the glenoid), all coracoid bone grafts healed. At last follow-up, the coverage rate of optimal glenoid circle was 89.6%-100%, with an average of 97.4%. The area of glenoid defect was 2.6%±1.3%, which significantly decreased when compared with preoperative (22.4%±5.4%) ( P<0.05). At last follow-up, no obvious degenerative changes of shoulder joint was observed. Conclusion: LU-tarjet procedure for recurrent anterior shoulder dislocation has good mid-term effectiveness with short operation time and few complications.

[Anatomical study of the limited osteotomy suture button fixation Latarjet procedure with coracoacromial ligament preservation].

Objective: To investigate the morphological characteristics of the glenohumeral joint (including the glenoid and coracoid) in the Chinese population and determine the feasibility of designing coracoid osteotomy based on the preoperative glenoid defect arc length by constructing glenoid defect models and simulating suture button fixation Latarjet procedure. Methods: Twelve shoulder joint specimens from 6 adult cadavers donated voluntarily were harvested. First, whether the coracoacromial ligament and conjoint tendon connected was anatomically observed and their intersection point was identified. The vertical distance from the intersection point to the coracoid, the maximum allowable osteotomy length starting from the intersection point, and the maximum osteotomy angle were measured. Next, the anteroinferior glenoid defect models of different degrees were randomly constructed. The arc length and area of the glenoid defect were measured. Based on the arc length of the glenoid defect of the model, the size of coracoid oblique osteotomy was designed and the actual length and angle of the coracoid osteotomy were measured. A limited osteotomy suture button fixation Latarjet procedure with the coracoacromial ligament and pectoralis minor preservation was performed and the position of coracoid block was observed. Results: All shoulder joint specimens exhibited crossing fibers between the coracoacromial ligament and the conjoint tendon. The vertical distance from the tip of the coracoid to the coracoid return point was 24.8-32.2 mm (mean, 28.5 mm). The maximum allowable osteotomy length starting from the intersection point was 26.7-36.9 mm (mean, 32.0 mm). The maximum osteotomy angle was 58.8°-71.9° (mean, 63.5°). Based on the anteroinferior glenoid defect model, the arc length of the glenoid defect was 22.6-29.4 mm (mean, 26.0 mm); the ratio of glenoid defect was 20.8%-26.2% (mean, 23.7%). Based on the coracoid block, the length of the coracoid osteotomy was 23.5-31.4 mm (mean, 26.4 mm); the osteotomy angle was 51.3°-69.2° (mean, 57.1°). There was no significant difference between the arc length of the glenoid defect and the length of the coracoid osteotomy ( P>0.05). After simulating the suture button fixation Latarjet procedure, the highest points of the coracoid block (suture loop fixation position) in all models located below the optimal center point, with the bone block concentrated in the anteroinferior glenoid defect position. Conclusion: The size of the coracoid is generally sufficient to meet the needs of repairing larger glenoid defects. The oblique osteotomy with preserving the coracoacromial ligament may potentially replace the traditional Latarjet osteotomy method.

The neurophysiological mechanisms of medial prefrontal-perirhinal cortex circuit mediating temporal order memory decline in early stage of AD rats.

The temporal component of episodic memory has been recognized as a sensitive behavioral marker in early stage of Alzheimer's disease (AD) patients. However, parallel studies in AD animals are currently lacking, and the underlying neural circuit mechanisms remain poorly understood. Using a novel AppNL-G-F knock-in (APP-KI) rat model, the developmental changes of temporal order memory (TOM) and the relationship with medial prefrontal cortex and perirhinal cortex (mPFC-PRH) circuit were determined through in vivo electrophysiology and microimaging technique. We observed a deficit in TOM performance during the object temporal order memory task (OTOMT) in APP-KI rats at 6 month old, which was not evident at 3 or 4 months of age. Alongside behavioral changes, we identified a gradually extensive and aggravated regional activation and functional alterations in the mPFC and PRH during the performance of OTOMT, which occurred prior to the onset of TOM deficits. Moreover, coherence analysis showed that the functional connectivity between the mPFC and PRH could predict the extent of future behavioral performance. Further analysis revealed that the aberrant mPFC-PRH interaction mainly attributed to the progressive deterioration of synaptic transmission, information flow and network coordination from mPFC to PRH, suggesting the mPFC dysfunction maybe the key area of origin underlying the early changes of TOM. These findings identify a pivotal role of the mPFC-PRH circuit in mediating the TOM deficits in the early stage of AD, which holds promising clinical translational value and offers potential early biological markers for predicting AD memory progression.