Background The health effects of environmental exposures are often characterized by complex interactions. However, evidence on the joint health effects of ambient oxidizing pollutants and air temperature in the cold regions of Northern China remains limited. Objective To examine the independent and interactive effects of atmospheric oxidizing pollutants and air temperature on daily mortality among residents of Hohhot. Methods Daily data on air quality, meteorological factors, and cause-specific mortality in Hohhot from 2018 to2023 were collected. A quasi-Poisson generalized additive model (GAM) combined with a distributed lag non-linear model (DLNM) was used to examine the effects of ambient oxidant pollutants [ozone (O₃), nitrogen dioxide (NO₂), and total oxidant (Oₓ)] and air temperature on daily circulatory and respiratory mortality. Potential interactions between oxidizing pollutants and temperature were evaluated using bivariate exposure–response surface models and quantified through stratified analyses. Results For each 10 μg·m⁻³ increase in O₃, O_X, and NO₂ concentrations, the strongest associations with circulatory disease mortality occurred at lag1, with excess risks (ERs) of 1.10% (95%CI: 0.50%, 1.71%), 1.84% (95%CI: 0.94%, 2.75%), and 1.49% (95%CI: 0.36%, 2.62%), respectively. The strongest associations of O₃ and O_X with respiratory disease mortality were observed at lag2, with ERs of 1.61% (95%CI: 0.61%, 2.62%) and 2.61% (95%CI: 1.61%, 3.62%), respectively. NO₂ showed the strongest cumulative association with respiratory disease mortality at lag02, with an ER of 3.22% (95%CI: 1.24%, 5.25%). High temperature exhibited immediate or short-term effects, while low temperature showed lagged effects. The exposure–response relationships between temperature and mortality risks for respiratory circulatory diseases were U-shaped. Positive additive interactions were observed between high temperature and high concentrations of O₃ and O_X. For the joint exposure to high temperature and high O₃, the relative excess risks due to interaction (RERIs) for circulatory and respiratory disease mortality were 0.131 (95%CI: 0.086, 0.176) and 0.279 (95%CI: 0.198, 0.360), respectively. For the joint exposure to high temperature and high O_X, the corresponding RERI values were 0.080 (95%CI: 0.038, 0.123) and 0.154 (95%CI: 0.074, 0.234), respectively. In contrast, high temperature and high NO₂ concentration exhibited antagonistic or attenuating interactions. Conclusion Ambient oxidizing pollutants, high temperature, and low temperature are independently associated with increased circulatory and respiratory disease mortality. High temperature combined with high concentrations of O₃ or O_X exerts positive additive interactions, with the respiratory system showing particular vulnerability. The mortality risks associated with NO₂ are more pronounced under low temperature conditions, whereas its interaction with high temperature appear antagonistic, suggesting a temperature-dependent risk-modifying effect.

ObjectiveTo screen for and validate key differentially expressed proteins in serum of patients with metabolic dysfunction‑associated fatty liver disease （MAFLD）， and to provide a basis for identifying diagnostic biomarkers and developing intervention strategies for this disease. MethodsA total of 20 patients who were diagnosed with MAFLD in the third affiliated hospital of Chengdu University of Traditional Chinese Medicine from December 2024 to January 2025 were enrolled as MAFLD group， and 20 healthy controls were enrolled as HC group. Demographic data and serum biochemical parameters were collected from both groups. Data-independent acquisition （DIA） quantitative proteomics was used to measure the relative expression levels of serum proteins， and related methods were used to obtain significantly differentially expressed proteins， including the gene ontology functional enrichment analysis， the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis， protein-protein interaction （PPI） network， Hub node interaction， and weighted gene co-expression network analysis （WGCNA）. Rats were given a high-fat diet to establish a model of MAFLD， and randomly assigned to the control group and model group. Serum biochemical parameters and inflammatory factors were measured， liver histopathological changes were observed， and the protein expression levels of MER proto-oncogene tyrosine kinase （MERTK） and matrix metalloproteinase-9 （MMP-9） in liver tissue were verified. The independent-samples t test was used for comparison of normally distributed continuous data between groups， while the Mann-Whitney U test was used for comparison of non-normally distributed continuous data or data with heterogeneity of variance between groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. ResultsCompared with the HC group， the MAFLD group had significant increases in the serum levels of aspartate aminotransferase （t=-7.348， P<0.05）， alanine aminotransferase （Z=5.088， P<0.05）， alkaline phosphatase （t=-3.943， P<0.05）， triglyceride （Z=2.070， P<0.05）， and high-density lipoprotein cholesterol （t=3.867， P<0.05）. A total of 3 559 proteins were identified by DIA serum proteomics， among which 160 differentially expressed proteins were mainly enriched in pathways including metabolic disorders， immune inflammatory response， and extracellular matrix remodeling. The PPI network and the Hub node analysis showed that serpin family E member 1， MMP-9， and intercellular cell adhesion molecule-1 were core regulatory proteins. WGCNA showed that the MEyellow module was significantly positively correlated with MAFLD phenotype （cor=0.55， P<0.001）， which was functionally enriched in the efferocytosis pathway. MERTK （P<0.001） and MMP-9 （P<0.001） showed the most significant differential expression in this module. A rat model of MAFLD was successfully established using a high-fat diet， and compared with the control group， the model group had enlarged， yellowish， and greasy liver and disordered structure of hepatic lobules， hepatocyte fatty degeneration， and inflammatory cell infiltration based on HE staining， as well as massive lipid droplet deposition based on oil red O staining， while no obvious fibrous cords were observed in Masson staining. Compared with the control group， the model group had significant increases in the serum levels of aspartate aminotransferase （t=-5.148， P<0.05）， alanine aminotransferase （t=-5.663， P<0.05）， total bilirubin （t=-13.061， P<0.05）， triglyceride （Z=-2.722， P<0.05）， total cholesterol （t=3.588， P<0.05）， and tumor necrosis factor-α （t=-16.741， P<0.05）， as well as significant increases in the protein expression levels of MERTK （t=-11.448， P<0.001） and MMP-9 （t=-10.875， P<0.001） in liver tissue. ConclusionMMP-9 and MERTK are abnormally expressed in MAFLD and may be used as potential diagnostic biomarkers for this disease.

Environmental toxicants have been linked to aging and age-related diseases. The emerging evidence has shown that the enhancement of detoxification gene expression is a common transcriptome marker of long-lived mice, Drosophila melanogaster, and Caenorhabditis elegans. Meanwhile, the resistance to toxicants was increased in long-lived animals. Here, we show that farnesoid X receptor (FXR) agonist obeticholic acid (OCA), a marketed drug for the treatment of cholestasis, may extend the lifespan and healthspan both in C. elegans and chemical-induced early senescent mice. Furthermore, OCA increased the resistance of worms to toxicants and activated the expression of detoxification genes in both mice and C. elegans. The longevity effects of OCA were attenuated in Fxr ^-/- mice and Fxr homologous nhr-8 and daf-12 mutant C. elegans. In addition, metabolome analysis revealed that OCA increased the endogenous agonist levels of the pregnane X receptor (PXR), a major nuclear receptor for detoxification regulation, in the liver of mice. Together, our findings suggest that OCA has the potential to lengthen lifespan and healthspan by activating nuclear receptor-mediated detoxification functions, thus, targeting FXR may offer to promote longevity.

Among tumor microenvironment (TME), the entire metabolic characteristics of tumor-resident cells are reprogrammed to benefit the expansion of tumor cells, which count on glutamine in large part to fuel the tricarboxylic acid cycle for energy generation and anabolic metabolism support. Endothelial cells that are abducted by tumor cells to form a pathological tumor vascular network for constructing the hypoxic immunosuppressive TME, also rely on glutaminolysis as the "engine" of angiogenesis. Additionally, the glutamine metabolic preference benefits the polarization of TAMs towards pro-tumoral M2 phenotype as well. Herein, we developed a type of siRNA micelleplexes (MH@siGLS1) to reverse immunosuppressive TME by targeting glutaminolysis within tumor-resident cells for tumor vasculature normalization- and TAMs repolarization-enhanced photo-immunotherapy. Tumor cell starvation and antioxidant system destruction achieved by MH@siGLS1-mediated glutaminolysis inhibition could promote photodynamic therapy efficacy, which was available to trigger immunogenic cell death for adaptive antitumor immune responses. Meanwhile, glutaminolysis inhibition of tumor endothelial cells and TAMs could realize tumor vascular normalization and TAMs repolarization for antitumor immunity amplification. This study provides a unique perspective on cancer treatments by focusing on the interrelations of metabolic characteristics and the biofunctions of various cell types within TME.

OBJECTIVES: To construct an intelligent analysis model for classifying fetal orientation during intrapartum ultrasound videos based on multi-feature fusion. METHODS: The proposed model consists of the Input, Backbone Network and Classification Head modules. The Input module carries out data augmentation to improve the sample quality and generalization ability of the model. The Backbone Network was responsible for feature extraction based on Yolov8 combined with CBAM, ECA, PSA attention mechanism and AIFI feature interaction module. The Classification Head consists of a convolutional layer and a softmax function to output the final probability value of each class. The images of the key structures (the eyes, face, head, thalamus, and spine) were annotated with frames by physicians for model training to improve the classification accuracy of the anterior occipital, posterior occipital, and transverse occipital orientations. RESULTS: The experimental results showed that the proposed model had excellent performance in the tire orientation classification task with the classification accuracy reaching 0.984, an area under the PR curve (average accuracy) of 0.993, and area under the ROC curve of 0.984, and a kappa consistency test score of 0.974. The prediction results by the deep learning model were highly consistent with the actual classification results. CONCLUSIONS The multi-feature fusion model proposed in this study can efficiently and accurately classify fetal orientation in intrapartum ultrasound videos.
Humans ; Female ; Ultrasonography, Prenatal/methods* ; Pregnancy ; Fetus/diagnostic imaging* ; Neural Networks, Computer ; Video Recording

Temporomandibular joint (TMJ) disc displacement is one of the most significant subtypes of temporomandibular joint disorders, but its etiology and mechanism are poorly understood. In this study, we elucidated the mechanisms by which destruction of inflamed collagen fibrils induces alterations in the mechanical properties and positioning of the TMJ disc. By constructing a rat model of TMJ arthritis, we observed anteriorly dislocated TMJ discs with aggravated deformity in vivo from five weeks to six months after a local injection of Freund's complete adjuvant. By mimicking inflammatory conditions with interleukin-1 beta in vitro, we observed enhanced expression of collagen-synthesis markers in primary TMJ disc cells cultured in a conventional two-dimensional environment. In contrast, three-dimensional (3D)-cultivated disc cell sheets demonstrated the disordered assembly of inflamed collagen fibrils, inappropriate arrangement, and decreased Young's modulus. Mechanistically, inflammation-related activation of the nuclear factor kappa-B (NF-κB) pathway occurs during the progression of TMJ arthritis. NF-κB inhibition reduced the collagen fibril destruction in the inflamed disc cell sheets in vitro, and early NF-κB blockade alleviated collagen degeneration and dislocation of the TMJ discs in vivo. Therefore, the NF-κB pathway participates in the collagen remodeling in inflamed TMJ discs, offering a potential therapeutic target for disc displacement.
Animals ; NF-kappa B/metabolism* ; Temporomandibular Joint Disorders/pathology* ; Temporomandibular Joint Disc/metabolism* ; Rats ; Rats, Sprague-Dawley ; Disease Models, Animal ; Male ; Collagen/metabolism* ; Cells, Cultured ; Joint Dislocations/pathology* ; Interleukin-1beta ; Arthritis, Experimental

Objective: To investigate the status quo and associated factors of drinking water knowledge, attitude and behavior among primary school students in rural areas, so as to provide evidence for health behavioral intervention of drinking water in primary school. Methods: Twentythree primary schools in rural area from Hebei, Henan, Shandong and Shanxi provinces were selected by using purposive sampling method from March 1 to April 27 in 2023. Selfdesigned questionnaires regarding knowledge, attitude and behavior of drinking water were distributed to all students in grade 3-6, and 2 173 valid questionnaires were obtained. Multivariate Logistic regression was used to analyze the influencing factors of drinking water knowledge, attitude and behavior of primary school students. Results: The attainment rates of drinking water knowledge, attitude and behavior level were 20.02%, 26.65%, and 31.20%, respectively, among primary school students. The median of daily water intake was 1 000 mL, and the average daily water intake was (1 172.99±771.89)mL. In addition, 66.31% of students water intake reached the minimum standard of 800 mL recommended. The results of multiple Logistic regression indicated that drinking water accessibility in school, health education of drinking water, and individual selfcontrol ability were positively correlated with the knowledge (OR=1.31, 1.57, 1.58), attitude (OR=2.07, 1.65, 1.73), behavior (OR=1.40, 1.49, 1.91) of drinking water and daily water intake (OR=1.41, 1.38, 1.20) (P<0.05). Conclusions Primary school students in rural areas are generally lack of appropriate health awareness on drinking water including knowledge, attitude and behavior. Schools should take targeted measures to focus on the cultivation of students selfcontrol ability, so as to improve students knowledge and attitudes of drinking water, and furthermore help students shape their healthy behaviors of drinking water.

Although fertility-preserving treatment strategies have demonstrated significant clinical efficacy in patients with early-stage endometrial cancer(EC)and atypical endometrial hyperplasia(AEH),some patients who experience recurrence still express a strong desire for fertility and request conservative retreatment.This poses new challenges for clinical management.This article reviews the latest research advances in retreatment for recurrent patients and synthesizes findings from previous studies to draw the following conclusions.First,before formulating a retreatment plan,it is crucial to comprehensively evaluate key factors such as tumor characteristics,fertility intentions,and overall health status of the patient.These factors collectively determine the feasibility and appropri-ateness of an individualized retreatment strategy.Second,studies have shown that retreatment options for AEH/EC are diverse,with high-dose oral progestin remaining the primary approach.Combining progestin with metformin,GnRH-a,and hysteroscopic resection can enhance treatment outcomes.Individualized treatment plans should be tailored to the specific conditions of each patient.Based on literature analysis,the complete remission(CR)rate of retreatment ranges from 81.1%to 88.6%,with a pregnancy rate of 26.5%-50.0%and a live birth rate of 14.3%-29.0%.However,the recurrence rate remains high at 24.5%-45.5%,significantly higher than that of initial treatment.This indicates that while retreatment has achieved some success in disease control and fertility preservation,the risk of recurrence still requires significant attention.Therefore,a strict monitoring and follow-up system must be established during retreatment.Additionally,studies have identified factors associated with a higher risk of recurrence,including age over 35,overweight or obesity,polycystic ovarian syndrome,metabolic syndrome,high pathological grade,and advanced clinical stage.On the other hand,pregnancy following CR,weight loss,and maintenance therapy serve as protective factors against disease recurrence.Patients are encouraged to actively engage in weight management during treatment and consider initiating assisted reproductive technology promptly after achieving CR to optimize pregnancy outcomes while minimizing the risk of recurrence.Future research should prioritize investigating precision treatment strategies informed by molecular classification and identifying predictive biomarkers,thereby enabling the development of more personalized and precise treatment plans tailored to indi-vidual patients.

Objective:To compare the efficacy of posteromedial combined with lateral Frosch approach versus anterior medial and lateral dual incision approach in open reduction and internal fixation for Schatzker type VI tibial plateau fractures.Methods:A retrospective cohort study was conducted to analyze the clinical data of 41 patients with Schatzker type VI tibial plateau fractures, who were admitted to the 940th Hospital of the Joint Logistics Support Force of the PLA from January 2018 to May 2024, including 23 males and 18 females, aged 34-79 years [(50.7±7.7)years]. Twenty-three patients underwent open reduction and internal fixation via the posteromedial combined with lateral Frosch approach (posterior approach group), while 18 patients underwent the same procedure via the anterior medial and lateral dual incision approach (anterior approach group). The following parameters were compared between the two groups: operation duration, intraoperative blood loss, postoperative drainage volume, depth of articular surface depression and tibial plateau width measured preoperatively, at 7 days, 3 months postoperatively, and at the last follow-up, medial proximal tibial angle (MPTA) and posterior proximal tibial angle (PPTA) measured at 7 days, 3 months postoperatively, and at the last follow-up, visual analogue scale (VAS) scores assessed preoperatively, at 7 days postoperatively, and at the last follow-up, American Knee Society (KSS) score and knee flexion range of motion assessed at 7 days, 3 months postoperatively, and at the last follow-up, fracture healing status at the last follow-up, and incidence of postoperative complications.Results:All the patients were followed up for 12-16 months [(14.3±2.1)months]. The operation duration was (119.6±11.8)minutes in the posterior approach group, which was significantly shorter than (140.3±10.6)minutes in the anterior approach group ( P<0.05). There were no statistically significant differences in intraoperative blood loss or postoperative drainage volume between the two groups ( P>0.05). No significant differences were found in the preoperative depth of articular surface depression or tibial plateau width between the two groups ( P>0.05). At 7 days, 3 months postoperatively, and at the last follow-up, the depth of articular surface depression was 0.8(0.6, 1.0)mm, 0.6(0.5, 0.8)mm, and 0.6(0.5, 0.7)mm in the posterior approach group, which were significantly shorter than 1.1(0.9, 1.3)mm, 0.8(0.7, 1.0)mm, and 0.8(0.7, 1.0)mm in the anterior approach group ( P<0.05). The tibial plateau width at the same time points was 71.0(69.1, 73.5)mm, 70.5(69.2, 72.9)mm, and 70.5(69.3, 72.5)mm in the posterior approach group, which were significantly shorter than 73.0(72.3, 74.2)mm, 71.5(71.0, 73.0)mm, and 71.5(71.1, 72.6)mm in the anterior approach group ( P<0.05). At 7 days, 3 months postoperatively, and at the last follow-up, the MPTA values were (87.4±0.7)°, (87.7±0.6)°, and (87.9±0.5)° in the posterior approach group, which were significantly larger than (85.2±2.5)°, (86.0±2.2)°, and (86.3±2.0)° in the anterior approach group ( P<0.01). The PPTA values at the same time points were (9.5±0.7)°, (9.0±0.5)°, and (8.6±0.4)° in the posterior approach group, which were significantly smaller than (11.2±1.0)°, (10.3±0.8)°, and (9.8±0.7)° in the anterior approach group ( P<0.01). There was no significant difference in the preoperative VAS score between the two groups ( P>0.05). At 7 days postoperatively and at the last follow-up, the VAS scores were 4.0(3.0, 5.0)points and 0.5(0.0, 2.0)points in the posterior approach group, which were significantly lower than 5.0(4.0, 5.0)points and 1.0(1.0, 3.0)points in the anterior approach group ( P<0.05). At 7 days, 3 months postoperatively, and at the last follow-up, the KSS scores were 62.5(57.0, 67.5)points, 75.5(72.0, 82.5)points, and 87.0(82.5, 93.5)points in the posterior approach group, which were significantly higher than 61.5(54.5, 63.0)points, 74.0(68.0, 79.0)points, and 85.5(78.0, 88.5)points in the anterior approach group ( P<0.05). The knee flexion range of motion was 90.0(85.0, 95.0)°, 115.0(109.0, 122.0)°, and 126.0(120.0, 130.0)° in the posterior approach group, which were significantly greater than 80.5(75.2, 85.8)°, 110.0(104.0, 115.0)°, and 119.0(113.0, 122.0)° in the anterior approach group ( P<0.05). At the last follow-up, all the fractures were healed in both groups. No statistically significant difference was found in the incidence of postoperative complications between the two groups ( P>0.05). Conclusion:Compared to the anterior medial and lateral dual incision approach, the posteromedial combined with lateral Frosch approach demonstrates superior advantages in operation duration, reduction quality, pain relief, functional recovery in the treatment of Schatzker type VI tibial plateau fractures, while the incidence of complications is comparable.

Objective To investigate the value of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)parameters in evaluating the short-term prognosis of laryngeal cancer patients after postoperative radiotherapy.Methods A case-control study was performed on 127 laryngeal cancer patients admitted to our hospital from January 2021 to December 2023.The patients underwent different tumor treatment followed by radical radiotherapy.According to tumor recurrence or not,they were divided into a recurrence group(n=50)and a non-recurrence group(n=77).DCE-MRI parameters,such as volume transfer constant(Ktrans),rate constant(Kep),and volume fraction of extracellular extravascular space(Ve),and clinical data were compared between the 2 groups.Multivariate logistic regression analysis was used to identify influencing factors for short-term prognosis after radiotherapy.Receiver operating characteristic(ROC)curves were plotted to evaluate the predictive efficacy of DCE-MRI parameters,and the area under the curve(AUC)was calculated.Results The recurrence group had significantly larger proportions of positive surgical margins,preoperative maximum lesion diameter≥4 cm,ulcerative lesions,stages N1～N3,and advanced stages Ⅲ～Ⅳ,and obviously higher Ktrans and Kep values but lower Ve valus than the non-recurrence group(P<0.05).Multivariate logistic regression analysis indicated that positive surgical margins,stages N1～N3,Ktrans,and Kep were independent risk factors for short-term prognosis,while Ve was a protective factor(P<0.05).ROC curve analysis showed that the AUC value of combination of Ktrans,Kep and Ve and of above 5 indicators in predicting short-term prognosis of postoperative radiotherapy for laryngeal cancer was 0.920(95%CI:0.858～0.961)and 0.923(95%CI:0.862～0.963),respectively.Though the AUC value of combined 3 parameters was significantly higher than that of the single indicator alone(P<0.05),there was no difference in the value between the combination of 3 parameters and the combined application of the 5 indicators.Conclusion DCE-MRI parameters Ktrans,Kep,and Ve are closely associated with short-term prognosis of postoperative radiotherapy for laryngeal cancer.Their combination has a good predictive efficacy for the short-term prognosis of the patients.