Development of a bioluminescent immunoassay based on Fc-specific conjugated antibody-nanoluciferase immunoreagents for determining aflatoxin B1.

Aflatoxin B1 (AFB1) is a potent carcinogen, and is among the most hazardous mycotoxins in agricultural products. Therefore, the development of sensitive and convenient detection methods for AFB1 is significant for food safety against mycotoxins. Herein, a bioluminescent enzyme immunoassay (BLEIA) was developed for ultrasensitive detection of AFB1, based on the novel Fc-specific antibody-nanoluciferase (Ab-Nluc) conjugates which were fabricated using an IgG-binding protein-assisted photo-conjugation strategy. In indirect competitive immunoassay format, the proposed BLEIA exhibited the detection limit of 0.0232 ng mL-1, which was 37.4-fold lower than that obtained using the classical enzyme-linked immunosorbent assay (ELISA) based on Ab-horseradish peroxidase (Ab-HRP) chemical conjugates (0.868 ng mL-1). Meanwhile, the BLEIA exhibited high accuracy and precision. Thus, the proposed Fc-specific Ab-Nluc conjugates-based BLEIA provides an ultrasensitive and reliable method for detecting toxins and has potential for use in food safety monitoring.

Tofacitinib for child-onset systemic lupus erythematosus.

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can cause diverse clinical manifestations in multiple organ systems. Child-onset SLE (cSLE) is associated with significantly higher morbidity and mortality than adult-onset SLE. The traditional treatments for SLE (glucocorticoids, antimalarials, conventional and biological disease-modifying antirheumatic drugs) often have significant adverse effects and may not fully control disease activity. Tofacitinib is an oral Janus kinase (JAK) inhibitor that inhibits the JAK-STAT pathway and has the potential to reduce SLE severity. Methods: cSLE patients who received tofacitinib and had at least one follow-up visit were retrospectively examined. Case histories, laboratory test results, and treatment regimens were analyzed at disease onset, initiation of tofacitinib treatment, and 1, 3, 6, 9, 12, 18, and 24 months after starting tofacitinib. Results: We examined 9 patients with refractory cSLE. All patients were female and the average age at diagnosis was 10.67 years. At initiation of tofacitinib, the average age was 13.28 years and the average disease duration was 2.62 years. Four patients experienced alleviation of symptoms and reduced their daily prednisone dosages; one of them also discontinued cyclosporine A and two of them also discontinued belimumab. The other 5 patients experienced no apparent benefit. Conclusion: Tofacitinib may provide clinical benefits for some patients with refractory cSLE, and can also allow reduction in the glucocorticoid dosage. Tofacitinib has the potential as an adjunctive treatment for some patients with cSLE.

Dual-energy computed tomography-based radiomics for differentiating patients with and without gout flares.

BACKGROUND: There is a current lack of data pertaining to the potential link between gout flares and dual-energy computed tomography radiomic features. This study aimed to construct and validate a comprehensive dual-energy computed tomography-based radiomics model for differentiating patients with and without gout flares. METHODS: The analysis included 200 patients, of whom 150 were confirmed to have experienced at least one flare in the past 12 months; the remaining 50 patients did not experience flares. The radiomic features of the tophi at the bilateral first metatarsophalangeal joints were extracted and analyzed. Optimal radiomic features were selected using the least absolute shrinkage and selection operator method, and logistic regression analysis was used to screen clinical characteristics and establish a clinical model. The optimal radiomic features were then combined with the identified independent clinical variables to develop a comprehensive model. The performances of the radiomic, clinical, and comprehensive models were evaluated using receiver operating characteristic curve analysis, calibration curves, and decision curve analysis. RESULTS: Four radiomic features distinguished patients with at least one flare from those without flares and were used to establish the radiomic model. Disease duration and hypertension were independent factors that differentiated flare occurrences. The radiomic, clinical, and comprehensive models showed favorable discrimination, with areas under the receiver operating characteristic curves of 0.76 (95% CI, 0.69-0.83), 0.72(95% CI, 0.63-0.80), and 0.79(95% CI, 0.73-0.86), respectively. The calibration curves (P > 0.05) showed that the differentiated values of the comprehensive model agreed well with the actual values. Decision curve analysis demonstrated that the comprehensive model achieved higher net clinical benefits than the use of either the radiomic or clinical model alone. CONCLUSION: The results of this study suggest that a radiomics model can distinguish patients with and without gout flares. Our proposed clinical radiomics nomogram can increase the efficacy of differentiating flare occurrence, which may facilitate the clinical decision-making process.

Prevalence and allergy-related risk factors of overactive bladder in children in Northeast China.

Objective: The objective of this study was to investigate the prevalence of overactive bladder (OAB) and its risk factors related to allergies among children in Northeastern China. Methods: A community survey on OAB was conducted in Northeast China from 1 April 2022 to 30 April 2022. The survey targeted children aged 5-14 years and utilized questionnaires. A total of 1,394 children were enrolled, and their parents were requested to fill out a questionnaire to provide basic information about the children. This encompassed details regarding the presence or absence of urgent urination unrelated to urinary tract infection, urinary tract infection, allergic rhinitis, asthma or cough variant asthma, atopic dermatitis, anaphylactic conjunctivitis, urticaria, constipation, and attention deficit hyperactivity disorder (ADHD). The prevalence of OAB was calculated. The chi-squared test was used to analyze OAB-related factors, which were subsequently included in the logistic regression model for multi-factor analysis. Results: The overall OAB prevalence was 10.7% (120 of 1,121), including 47 mild cases (39.2%), 71 moderate cases (59.1%), and 2 severe cases (1.7%). OAB prevalence decreased with age (p < 0.05). The risk factors associated with OAB were allergic asthma (OR = 1.87, 95%CI: 1.12-3.13), atopic dermatitis (OR = 2.45, 95%CI: 1.61-3.73), anaphylactic conjunctivitis (OR = 1.61, 95%CI: 1.07-2.42), and urticaria (OR = 1.93, 95%CI: 1.40-2.66). Conclusion: OAB prevalence among children in Northeastern China was found to be 10.7%, with its risk factors being allergic asthma, anaphylactic conjunctivitis, urticaria, and atopic dermatitis. The identification of allergy-related risk factors may provide new ideas for the prevention and treatment of OAB.

Association between gray matter regional structural-functional connectivity couplings and visual memory in major depressive disorder.

Alterations in structural-functional (SC-FC) coupling have been linked to major depressive disorder (MDD). A newly developed algorithm for regional-specific SC-FC coupling analysis shows potential in advancing psychiatric research. In this study, we calculated the gray matter regional-specific SC-FC coupling of 114 MDD patients and 131 healthy controls (HCs). The delayed matching to sample (DMS) and Pattern Recognition Memory (PRM) subtests of the computerized Cambridge Neurocognitive Test Automated Battery (CANTAB) were used to evaluate visual memory. We found that the Xgboost model exhibited robust discriminative performance (Area under the ROC curve [95% CI]: 0.75 [0.65 to 0.85], Accuracy [95% CI]: 0.73 [0.63 to 0.84], Sensitivity [95% CI]: 0.65 [0.53 to 0.76], Specificity [95% CI]: 0.82 [0.77 to 0.87]). MDD patients showed lower SC-FC coupling in the left inferior frontal orbital gyrus (IFGorb_L) and the right inferior occipital gyrus (IOG_R) and higher SC-FC coupling in the left superior temporal pole (TPOsup_L) and the right middle temporal pole (TPOmid_R) than HCs. SC-FC coupling of IFGorb_L negatively correlated with current duration of illness (r = -0.26, P = 0.007), IOG_R negatively correlated with HAMD-17 cognitive factor score (r = -0.24, P = 0.011), while TPOsup_L positively correlated with percent correct in PRM delayed task among MDD patients (r = 0.31, P = 0.003). In conclusion, the study suggested that altered regional SC-FC coupling may be involved in MDD pathophysiology and associated with visual memory impairment.

Inhibitory effects characteristics of polysaccharide of Polygonati Rhizome on cytochrome P450 enzymes.

PURPOSE: As the major active ingredient of Polygonatum sibriricum Red., polysaccharide of Polygonati Rhizome (PSP) has been reported to possess various pharmacological activities, especially for the treatment of chronic disorders in the elderly. This study evaluated the effect of PSP on the activities of major cytochrome P450 enzymes (CYP450) isoforms, aiming to provide theoretical reference for its co-prescription with other drugs and prevent the risk of adverse drug-drug interaction. METHODS: The activities of CYP450 isoforms were assessed in human liver microsomes with specific probe substances. Through Lineweaver-Burk fitting models, the effect of PSP on the activity of inhibited CYP450 isoforms was characterized by competitive and non-competitive models. Dose-dependent and time-dependent experiments were also performed to completely understand the inhibition. RESULTS: Among experimental isoforms, PSP significantly inhibited the activities of CYP2C9, 2D6, and 3A4 in a concentration-dependent manner with IC50 values of 14.01, 17.63, and 5.33 µM. The inhibition of CYP2C9 and 2D6 was best fitted with the competitive model with the Ki values of 7.15 and 8.92 µM, respectively, while the inhibition of CYP3A4 was non-competitive with the Ki value of 2.63 µM. Additionally, the inhibition of CYP3A4 by PSP also showed time-dependent characteristics with the inhibition parameters, KI of 1.273 µM-1 and Kinact of 0.036 min-1. CONCLUSION: PSP exerted moderate inhibition on CYP2C9 and 2D6 and strong inhibition of CYP3A4. The dosage of CYP2C9-, 2D6-, and 3A4-metabolized drugs should be adjusted when co-administrated with PSP and its sourced herbs.

Effects of depression and cognitive impairment on increased risks of incident dementia: a prospective study from three elderly cohorts.

Depression is usually accompanied with cognitive impairment and increases risk of incident dementia. However, evidence has been limited on the effect size of depression with cognitive impairment and their synergistic effect on future dementia. To explore this, we examined three large cross-country population-based prospective cohorts. Depressive symptoms were assessed by epidemiologic scale, while cognitive impairment was defined by subjective cognitive tests. Dementia was ascertained by self-reported physician-diagnosed conditions. Cox proportional hazard models were employed to determine the hazard ratio (HR) and 95% confidence interval (95% CI), with adjustments of potential confounding variables. Addictive and multiplicative interactions were calculated to evaluate the synergistic effect. A total of 64,706 participants were included at baseline (mean age: 63.9, female: 55.2%), where 4197 (6.5%) individuals had depressive symptoms only, 28,175 (43.5%) individuals had cognitive impairment only, 11,564 (17.9%) individuals had both, and 20,770 (32.1%) individuals had neither. Compared with the neither group, all the other three groups had higher risks of subsequent dementia (depression only: HR 1.65, 95% CI 1.26-2.17; cognitive impairment only: HR 2.71, 95% CI 2.33-3.14; depression with cognitive impairment: HR 3.51, 95% CI 2.95-4.17). There was insignificant additive (RERI, 0.15, 95% CI -0.45-0.75; AP, 0.042, 95% CI -0.13-0.21; SI, 1.06, 95% CI 0.83-1.37) and multiplicative (0.78, 95% CI 0.58-1.06) interaction between depression and cognitive impairment on subsequent dementia. We found depression with cognitive impairment has higher risks of dementia than either condition alone and no significant synergistic effect exists between these two factors.

Relationship of prefrontal cortex activity with anhedonia and cognitive function in major depressive disorder: an fNIRS study.

Background: Major depressive disorder (MDD) is associated with deficits in cognitive function, thought to be related to underlying decreased hedonic experiences. Further research is needed to fully elucidate the role of functional brain activity in this relationship. In this study, we investigated the neurofunctional correlate of the interplay between cognitive function and hedonic experiences in medication-free MDD using functional near-infrared spectroscopy (fNIRS). Methods: We examine differences of brain activation corresponding to the verbal fluency test (VFT) between MDD patients and healthy controls (HCs). Fifty-six MDD patients and 35 HCs underwent fMRI scanning while performing the VFT. In exploratory analyses, cognitive performance, as assessed by the Cambridge Neuropsychological Test Automated Battery (CANTAB), four dimensions of hedonic processing (desire, motivation, effort, and consummatory pleasure) measured by the Dimensional Anhedonia Rating Scale (DARS), and relative changes in oxygenated hemoglobin concentration during the VFT were compared across groups. Results: Patients with MDD demonstrated impairments in sustained attention and working memory, accompanied by lower total and subscale scores on the DARS. Compared to healthy controls, MDD patients exhibited reduced activation in the prefrontal cortex (PFC) during the VFT task (t = 2.32 to 4.77, p < 0.001 to 0.02, FDR corrected). DARS motivation, desire, and total scores as well as sustained attention, were positively correlated with activation in the dorsolateral PFC and Broca's area (p < 0.05, FDR corrected). Conclusions: These findings indicate that changes in prefrontal lobe oxygenated hemoglobin levels, a region implicated in hedonic motivation and cognitive function, may serve as potential biomarkers for interventions targeting individuals with MDD. Our results corroborate the clinical consensus that the prefrontal cortex is a primary target for non-invasive neuromodulatory treatments for depression.

Construction of the whole-process nursing service system for day surgery patient based on the Kano model: A pilot cluster randomized controlled trial.

Objective: The types and number of day surgeries have significantly increased, but the construction of the whole process nursing service system (WPNSS) for preoperative education, intraoperative cooperation, postoperative knowledge, and follow-up for day surgery patients is still in the exploratory stage. The aim of this study is to establish the WPNSS for day surgery patients using the Kano model and to preliminarily assess its efficacy. Methods: WPNSS for day surgery was devised leveraging Internet hospital information systems and patient mobile terminals (WeChat), guided by the World Health Organization's conceptual framework for scaling-up strategies. The system was methodically developed, progressing from defining the overall framework to delineating modular functions and developing specific educational materials and tools. A pilot test was conducted in a hospital in China. Results: WPNSS, a patient-centric remote education and monitoring system, seamlessly amalgamates health education, online consultations, and follow-up functionalities; offering semi-automated surgical consultations, inquiry services, and postoperative follow-ups, as well as autonomously disseminating perioperative health education content. Comprising both client and server components, patients utilizing the system are inclined to recommend day surgery at the hospital to others. Conclusions: WPNSS delivers personalized and precise health education, consultation, and postoperative follow-up services for day surgery patients. Current results suggest that the WPNSS may improve patients' experience. Trial Registration: Chinese Clinical Trial Register (ChiCTR2200066782).

A Risk Correlative Model for Sleep Disorders in Chinese Older Adults Based on Blood Micronutrient Levels: A Matched Case-Control Study.

BACKGROUND: The physical abilities of older adults decline with age, making them more susceptible to micronutrient deficiency, which may affect their sleep quality. OBJECTIVES: This study aimed to construct a risk correlative model for sleep disorders in Chinese older adults based on blood micronutrient levels. METHODS: In this matched case-control study, we recruited 124 participants with sleep disorders and 124 matched controls from the Tianjin Elderly Nutrition and Cognition cohort in China. Micronutrient levels in whole blood were measured using the dried blood spot technique. We compared the differences in micronutrient levels between the two groups and also constructed a receiver operating characteristic (ROC) model and nomogram for sleep disorders. RESULTS: In comparison to the control group, the sleep disorders group showed lower levels of blood vitamin A, vitamin E (VE), folate, magnesium, copper, iron, and selenium (Se) in the univariate analysis (p < 0.05). The ROC curve analysis indicated that the combination of VE + folate + Se may have an excellent diagnostic effect on sleep disorders, with an area under the curve of 0.964. This VE + folate + Se was integrated into a nomogram model to demonstrate their relationship with sleep disorders. The consistency index of the model was 0.88, suggesting that the model assessed sleep disorders well. CONCLUSIONS: The sleep disorders risk correlative model constructed by the levels of VE, folate, and Se in whole blood might show good performance in assessing the risk of sleep disorders in older adults.

Multi-omics landscape of Interferon-stimulated gene OASL reveals a potential biomarker in pan-cancer: from prognosis to tumor microenvironment.

Background: OASL (Oligoadenylate Synthetase-Like), an interferon-induced protein in the OAS family, plays a significant role in anti-viral response. Studies have demonstrated its association with prognosis of certain tumors. However, the mechanism through which OASL affects tumors is unclear. A systemic pan-cancer study of OASL needs to be illustrated. Methods: Analysis of OASL expression across 33 tumors was conducted utilizing TCGA, GTEx and CPTAC databases. COX and Log-Rank regressions were employed to calculate the prognosis. We validated the impact of OASL on apoptosis, migration, and invasion in pancreatic cancer cell lines. Moreover, we employed seven algorithms in bulk data to investigate the association of OASL expression and immune cell infiltration within tumor immune microenvironment (TIME) and ultimately validated at single-cell transcriptome level. Results: We discovered elevated expression of OASL and its genetic heterogeneity in certain tumors, which link closely to prognosis. Validation experiments were conducted in PAAD and confirmed these findings. Additionally, OASL regulates immune checkpoint ligand such as programmed death ligand 1 (PD-L1), through IFN-γ/STAT1 and IL-6/JAK/STAT3 pathways in tumor cells. Meanwhile, OASL affects macrophages infiltration in TIME. By these mechanisms OASL could cause dysfunction of cytotoxic T lymphocytes (CTLs) in tumors. Discussion: Multi-omics analysis reveals OASL as a prognostic and immunological biomarker in pan-cancer.

The association between dietary quality, sleep duration, and depression symptoms in the general population: findings from cross-sectional NHANES study.

BACKGROUND: Unhealthy lifestyles, which include unhealthy diet and unhealthy sleep duration, have been widely recognized as modifiable risk factors for depressive symptoms. This study aims to explore the associations between dietary quality, sleep duration, and depression symptoms, as well as their combined effects. METHODS: The NHANES 2007 to 2014 cycles provided the data for this study, in which 19,134 adults aged 20 years and older were included. Unhealthy diet, measured using an average Healthy Eating Index (HEI)-2015 score below the 60th percentile, and unhealthy sleep duration, measured as sleep duration at night less than 7 h or greater than/equal to 9 h, were the primary exposures. Then participants were divided into four different lifestyles. A weighted-multivariable logistic regression was employed, controlling for relevant variables. Furthermore, stratified analyses were conducted to assess the robustness of the findings and identify potential high-risk groups. RESULTS: The overall prevalence of depressive symptoms among all participants was 8.44%. Among the participants, 56.58% met the criteria for healthy sleep duration, and 24.83% scored at or above the 60th percentile on the HEI-2015. Unhealthy diet (OR: 1.40, 95% CI: 1.18-1.67, p < 0.001) and unhealthy sleep duration (OR: 1.94, 95% CI: 1.63-2.31, p < 0.001) exhibited positive associations with depression symptoms. Individuals who maintained an unhealthy diet but healthy sleep duration (OR: 1.60, 95% CI: 1.20-2.13, p = 0.002), healthy diet but unhealthy sleep duration (OR: 2.50, 95% CI: 1.64-3.80, p < 0.001), or an unhealthy diet and unhealthy sleep duration (OR: 2.91, 95% CI: 2.16-3.92, p < 0.001) were significantly associated with depressive symptoms compared to those with a healthy diet and healthy sleep duration, respectively. In stratified analyses, females, middle-aged individuals, those with a college degree or higher education, and individuals who do not meet the recommended level of physical activity exhibit heightened susceptibility to depressive symptoms when exposed to unhealthy diet and unhealthy sleep duration. CONCLUSION: In summary, our study suggests that individuals affected by the individual and synergistic effect of an unhealthy diet and unhealthy sleep duration are more susceptible to experiencing depressive symptoms.

Vitamin D and Gestational Diabetes Mellitus in the IEU OpenGWAS Project: A Two-Sample Bidirectional Mendelian Randomization Study.

BACKGROUND: Gestational diabetes mellitus (GDM) is one of the most prevalent pregnancy problems, and there is still debate over the relationship between vitamin D and GDM. OBJECTIVES: Our objective is to investigate the correlation between vitamin D and GDM by employing Mendelian randomization (MR) with summary data obtained from genome-wide association studies (GWAS). METHODS: Data on exposures and outcomes, namely vitamin D, vitamin D insufficiency, and GDM, were acquired from the IEU OpenGWAS Project. Bidirectional MR analysis was performed utilizing the inverse variance weighted (IVW) method as the principal analytical approach. The complementary approaches employed in this study encompassed weighted median, simple mode, weighted mode, and MR-Egger regression. A series of sensitivity analysis were conducted in order to assess the reliability of the obtained results. RESULTS: The data were acquired from the IEU OpenGWAS Project. Following the application of the three assumptions of MR, 13 single nucleotide polymorphisms (SNPs) were included in the MR analysis for vitamin D levels and vitamin D deficiency on GDM, and 10 and 26 SNPs were included for GDM on vitamin D levels and deficiency, respectively. The findings from the IVW analysis revealed a significant positive correlation between vitamin D levels and GDM (OR = 1.057, 95% CI: 1.011-1.104, p = 0.015). Conversely, a negative correlation was seen between vitamin D deficiency and GDM (OR = 0.979, 95% CI: 0.959-0.999, p = 0.039). The results of the reverse MR study revealed no evidence of reverse causation between GDM and vitamin D. The findings from multiple MR approaches were in line with the direction of IVW analysis. Sensitivity analysis revealed no evidence of heterogeneity, pleiotropy, or outliers, suggesting the robustness of the results. CONCLUSIONS: There exists a causal association between vitamin D and GDM, whereby vitamin D levels serve as a risk factor for GDM.

Human resource allocation status and equity research of Centers for Disease Control and Prevention in China from 2016 to 2020.

Background: In recent years, the development of global public health has become a matter of great concern and importance for governments worldwide. China, as the largest developing country, plays a crucial role in shaping the development of the public health and its ability to respond to sudden public health emergencies through the fairness of its human resource allocation in center for disease control and prevention (CDC). Objective: This study aims to analyze the situation of health human resource allocation in the China Centers for Disease Control and Prevention (China CDCs), assess the fairness of the allocation, and provide reference for the rational allocation of human resources. Methods: We selected data from the China Health Statistics Yearbook on healthcare technical personnel, other technical personnel, managerial personnel, and workforce technical personnel of China CDCs for the period of 2016-2020. We utilized the Health Resource Density Index to evaluate the level of human resource allocation in China CDCs. Additionally, we used the Gini coefficient and Theil index to assess the fairness of human resource allocation in China CDCs from both a population and geographical perspective. Results: Firstly, the educational qualifications and professional titles of CDC staff have improved, but the workforce is aging. Secondly, HRDI development trends vary among different personnel types and regions with varying levels of economic development. Finally, the results of the Gini coefficient and Theil index indicate that population distribution fairness is better than geographical distribution fairness. Overall, the unfair population distribution is primarily due to regional disparities. Conclusion: The China CDCs should tailor different standards for the allocation of health human resources based on regional characteristics, aiming to enhance the accessibility of health human resources in various regions and achieve equitable allocation.

ß-hydroxybutyrate and mitochondria mediate the association between medium-chain fatty acids, DHA and mild cognitive impairment: a nested case-control study.

BACKGROUND: Medium-chain fatty acids (MCFAs) and docosahexaenoic acid (DHA) could affect the occurrence of mild cognitive impairment (MCI). ß-hydroxybutyrate (BHB), mitochondrial DNA copy number (mtDNAcn) and mitochondrial DNA (mtDNA) deletions might be their potential mechanisms. This study aimed to explore the relationship between MCFAs, DHA and MCI, and potential mechanisms. METHODS: This study used data from Tianjin Elderly Nutrition and Cognition (TENC) cohort study, 120 individuals were identified with new onset MCI during follow-up, 120 individuals without MCI were selected by 1:1 matching sex, age, and education levels as the control group from TENC. Conditional logistic regression analysis and mediation effect analysis were used to explore their relationship. RESULTS: Higher serum octanoic acid levels (OR: 0.633, 95% CI: 0.520, 0.769), higher serum DHA levels (OR: 0.962, 95% CI: 0.942, 0.981), and more mtDNAcn (OR: 0.436, 95% CI: 0.240, 0.794) were associated with lower MCI risk, while more mtDNA deletions was associated with higher MCI risk (OR: 8.833, 95% CI: 3.909, 19.960). Mediation analysis suggested that BHB and mtDNAcn, in series, have mediation roles in the association between octanoic acid and MCI risk, and mtDNA deletions have mediation roles in the association between DHA and MCI risk. CONCLUSION: Higher serum octanoic acid and DHA levels were associated with lower MCI risk. Octanoic acid could affect the incidence of MCI through BHB, then mitochondria function, or through mitochondria function, or directly. Serum DHA level could affect the incidence of MCI through mitochondria function, or directly.

A study on the mediating role of serum hormones in the effects of heavy metals on preeclampsia.

Exposure to environmental heavy metals may pose a risk factor for developing preeclampsia (PE) modified through intervention. This case-control study aimed to investigate the association between serum heavy metal concentrations and PE in pregnant women and whether hormones served as mediating factors in the impact of heavy metals on PE. From October 2020 to 2022, 160 patients with PE and 160 pregnant women with normal deliveries were recruited at Dongguan Songshan Lake Central Hospital. Serum concentrations of manganese (Mn), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), cadmium (Cd), lead (Pb), ß-human chorionic gonadotropin (ß-hCG), progesterone (P), estradiol (E2), testosterone (T), cortisol (Cort), and cortisone (Cor) were measured. Logistic, restricted cubic splines, weighted quantile sum and multivariate linear regression models were employed to account for different aspects and explore the relationships among heavy metals, hormones, and PE. Mediation model analysis was performed to assess the role of hormones in mediation. The median concentrations of Mn, E2, and Cort were lower in the PE group than in the control group. The median concentrations of Cu, Zn, ß-hCG, and T were higher in the PE than in the control. Mn, E2, and Cort showed negative associations with PE, while Cu, Zn, ß-hCG, and T demonstrated positive associations, as determined through logistic regression. Mn, Cu, and Zn displayed linear dose-response relationships with PE. Zn and Cu had high weights in the positive association model of mixed heavy metal exposure with PE. The mediation analysis revealed that serum E2, P, T, Cort, and Cort/Cor might be potential mediators of the association between heavy metals (Mn, Cu, and Zn) and PE.

H3K18 Lactylation Potentiates Immune Escape of Non-Small Cell Lung Cancer.

Recently discovered epigenetic modification lysine lactylation contributes to tumor development and progression in several types of cancer. In addition to the tumor-intrinsic effects, histone lactylation may mediate tumor microenvironment remodeling and immune evasion. In this study, we observed elevated pan-lysine lactylation and histone H3 lysine 18 lactylation (H3K18la) levels in non-small cell lung cancer (NSCLC) tissues, which was positively correlated with poor patient prognosis. Interruption of glycolysis by 2-deoxy-D-glucose and oxamate treatment and silencing of lactate dehydrogenase A and lactate dehydrogenase B reduced H3K18la levels and circumvented immune evasion of NSCLC cells by enhancing CD8+ T-cell cytotoxicity. Mechanistically, H3K18la directly activated the transcription of pore membrane protein 121 (POM121), which enhanced MYC nuclear transport and direct binding to the CD274 promoter to induce PD-L1 expression. In a mouse NSCLC xenograft model, combination therapy with a glycolysis inhibitor and an anti-PD-1 antibody induced intratumoral CD8+ T-cell function and exhibited strong antitumor efficacy. Overall, this work revealed that H3K18la potentiates the immune escape of NSCLC cells by activating the POM121/MYC/PD-L1 pathway, which offers insights into the role of posttranslational modifications in carcinogenesis and provides a rationale for developing an epigenetic-targeted strategy for treating NSCLC. Significance: H3K18 lactylation supports immunosuppression in non-small cell lung cancer by inducing POM121 to increase MYC activity and PD-L1 expression, which can be reversed by metabolic reprogramming and immunotherapy treatment.

[Evaluation of efficacy of denture occlusal plate combined with comprehensive physical therapy for temporomandibular joint disc displacement without reduction].

PURPOSE: To explore the efficacy of denture occlusal plate combined with comprehensive physical therapy for temporomandibular joint disc displacement without reduction(ADDwoR). METHODS: Sixty patients of ADDwoR and dentition defect or severely worn teeth who visited the Department of Orthodontics and Prosthodontics of Hengshui People's Hospital from January 2019 to December 2020 were selected and randomly divided into denture occlusal plate group (group A) and denture occlusal plate + comprehensive physical therapy group (group B) according to the treatment methods. Maximum mouth opening (MMO) and visual analog pain score(VAS) among all patients were recorded before treatment and every three weeks during three months of treatment. Cone-beam CT(CBCT) was taken before and 3 months after treatment. The changes in clinical efficacy indicators before and after treatment and CBCT data between the two groups were analyzed. Statistical analysis was performed with SPSS 26.0 software package. RESULTS: The differences of VAS of group A and B were statistically significant from before treatment to three weeks after treatment(P＜0.05), and group B decreases more. From 3 weeks after treatment, there was a significant difference of group B for MMO and VAS before treatment (P＜0.05). From 9 weeks after treatment, there was a significant difference of group A for MMO before treatment (P＜0.05), but there was no significant difference in MMO and VAS between group A and B(P＞0.05). CBCT showed narrowed anterior joint space, widened posterior joint space, enlarged superior joint space, decreased horizontal angle of the condyle and increased slope of joint nodules (P＜0.05). The difference between joint depth, anteroposterior diameter of the condyle, internal and external diameter was not significant (P＞0.05). There was significant differences in anterior, superior, and posterior joint space, condylar level angle, and slope of joint nodules of group B compared with group A(P＜0.05). CONCLUSIONS: Denture occlusal plate can effectively improve symptoms of ADDwoR, and denture occlusal plate combined with comprehensive physical therapy can quickly improve mouth opening and reduce pain in the joint area.

[The association between preterm birth and hypertension]. / æ—©äº§ä¸Žé«˜è¡€åŽ‹çš„å ³ç³».

In recent years, the number of premature births worldwide has been increasing, and their long-term prognoses, particularly the cardiovascular outcomes of preterm individuals in adulthood, have become a growing concern. Adults who were born prematurely are at a higher risk for cardiovascular diseases, which may be related to changes in cardiovascular structure, renal structure alterations, changes in body composition, and overactivation of the hypothalamic-pituitary-adrenal axis. To improve the outcomes for preterm individuals, long-term follow-up monitoring and effective prevention and treatment measures are necessary. This article aims to review the relevant literature, summarize the risks and mechanisms of hypertension during childhood and adulthood in those born prematurely, and enhance awareness and understanding of the risk of hypertension in adults who were born prematurely.

The impact of admission modes on the treatment outcome and in-hospital mortality rate of STEMI patients undergoing PPCI.

The current research on ST elevation myocardial infarction (STEMI) patients has been mostly limited to Door-to-Balloon (D-to-B) time. This study aimed to compare the effects of different hospital admission modes to on the time metrics of patients undergoing primary percutaneous coronary intervention (PPCI). It also examined the effects of these modes on in-hospital mortality and other influencing factors. The goal was to prompt healthcare facilities at all levels, including chest hospitals, the Centers for Disease Control and Prevention (CDC), and communities to take measures to enhance the treatment outcomes for patients with STEMI. A total of 1053 cases of STEMI patients admitted to Tianjin Chest Hospital from December 2016 to December 2023 and successfully underwent PPCI were selected for this study. They were divided into three groups based on the admission modes: the ambulances group (363 cases), the self-presentation group (305 cases), and the transferred group (385 cases). Multivariate logistic regression was used to explore the impact of different modes of hospital admission on the standard-reaching rate of key treatment time metrics. The results showed that the S-to-FMC time of transferred patients (OR = 0.434, 95% CI 0.316-0.596, P < 0.001) and self-presentation patients (OR = 0.489, 95% CI 0.363-0.659, P < 0.001) were more likely to exceed the standard than that of ambulance patients; The cath lab pre-activation time of self-presented patients was also less likely to meet the standard than that of ambulance patients (OR = 0.695, 95% CI 0.499-0.967, P = 0.031); D-to-W time of self-presentation patients was less likely to reach the standard than that of ambulance patients (OR = 0.323, 95% CI 0.234-0.446, P < 0.001);However, the FMC-to-ECG time of self-presentation patients was more likely to reach the standard than that of ambulance patients (OR = 2.601, 95% CI 1.326-5.100, P = 0.005). The Cox proportional hazards model analysis revealed that for ambulance patients, the time spent at each key treatment time point is shorter, leading to lower in-hospital mortality rate (HR0.512, 95% CI 0.302-0.868, P = 0.013) compared to patients admitted by other means. We found that direct arrival of STEMI patients to the PCI hospital via ambulance at the onset of the disease significantly reduces the S-to-FMC time, FMC-to-ECG time, D-to-W time, and catheterization room activation time compared to patients who self-present. This admission mode enhances the likelihood of meeting the benchmark standards for each time metric, consequently enhancing patient outcomes.