Objective: To investigate the association between screen time (ST) during leisure time and anxiety-depression symptoms among middle school students, so as to provide a basis for formulating relevant intervention measures. Methods: From November to December 2023, a stratified cluster random sampling method was used to select 2 542 students from junior and senior high school in Taiyuan City. A self designed questionnaire, the Generalized Anxiety Disorder Scale (GAD-7), and the Patient Health Questionnaire (PHQ-9) were used to investigate ST and anxiety/depression symptoms among middle school students. The Logistic regression model was used to explore the association of ST with symptoms of anxiety and depression, as well as with anxiety and depression comorbiditles (CAD). Results: The detection rates of anxiety symptoms, depression symptoms, and CAD were 13.69%, 15.77%, and 10.11%, respectively. The median ST was 2.00 h/d [interquartile range ( IQR =2.38) for weekly averages], with 0.33 h/d ( IQR =1.67) on work days and 5.00 h/d ( IQR=5.50) on rest days. Logistic regression analysis indicated that the total ST of mobile phones during rest days ( OR =1.07, 1.10, 1.11) and the averages ST of mobile phones over a week ( OR = 1.20 , 1.22, 1.29), as well as the total ST of all screen types during rest days ( OR =1.04, 1.04, 1.05) and the averages ST of all screen types over a week ( OR =1.08, 1.09, 1.21) were positively correlated with anxiety symptoms, depression symptoms, and CAD (all P <0.01). Conclusions Among middle school students in Taiyuan City, screen time is positively correlated with symptoms of anxiety or depression and the comorbidity of anxiety and depression, especially smartphone screen time and weekend screen use. Therefore, measures should be implemented to reduce unnecessary screen time among middle school students, especially the use of mobile phones, in order to mitigate the occurrence of anxiety and depression.

The p21-activated kinase 4 (PAK4), a key regulator of malignancy, is negatively correlated with immune infiltration and has become an emergent drug target of cancer therapy. Given the lack of high efficacy PAK4 inhibitors, we herein reported the identification of a novel inhibitor 13 bearing a tetrahydrobenzofuro[2,3-c]pyridine tricyclic core and possessing high potency against MIA PaCa-2 and Pan02 cell lines with IC₅₀ values of 0.38 and 0.50 μmol/L, respectively. This compound directly binds to PAK4 in a non-ATP competitive manner. In the mouse Pan02 model, compound 13 exhibited significant tumor growth inhibition at a dose of 100 mg/kg, accompanied by reduced levels of PAK4 and its phosphorylation together with immune infiltration in mice tumor tissue. Overall, compound 13 is a novel allosteric PAK4 inhibitor with a unique tricyclic structural feature and high potency both in vitro and in vivo, thus making it worthy of further exploration.

Objective:To explore the relationship between thyroid hormone sensitivity and metabolic dysfunction-associated steatotic liver disease(MASLD) in a population with normal thyroid function, with a particular focus on sex-specific differences.Methods:This retrospective study included 41 355 euthyroid cases who underwent routine health examinations at the Health Management Centre of the Second Affiliated Hospital of Dalian Medical University from January 2014 to December 2023 were included. The free triiodothyronine(FT 3) to free thyroxine(FT 4) ratio(FT 3/FT 4) was calculated in order to reflect the peripheral sensitivity of the thyroid gland. Similarly, thyroid feedback quantile-based index(TFQI), thyrotrophic thyroxine resistance index(TT 4RI), and the FT 3-based TFQI-derived index(TFQI-FT 3) were calculated in order to reflect the central sensitivity of the thyroid gland. A Logistic regression was employed to analyse the effect of sex-specific thyroid hormone sensitivity indices on the prevalence of MASLD. The restricted cubic spline was used to analyse the non-linear relationship between the thyroid sensitivity hormone indices and MASLD. Furthermore, the correlation between the thyroid hormone sensitivity indices and MASLD in different subgroups was also analysed. Results:The prevalence of MASLD in the study population was 28.8%. After adjusting the model for confounders, the risk of MASLD increased by 7%, 3%, 10%, and 5% for each standard deviation increase in FT 3/FT 4, TFQI, TFQI-FT 3, and TT 4RI in the total population, respectively. The risk of MASLD increased by 6% and 5% for each standard deviation increase in FT 3/FT 4 and TFQI-FT 3 in men, respectively. For each standard deviation increase in FT 3/FT 4, TFQI, TFQI-FT 3, and TT 4RI in women, the risk of MASLD increased by 6%, 5%, 11%, and 5%, respectively. Higher FT 3/FT 4 and TFQI-FT 3 were positively associated with the risk of developing MASLD in men, and higher FT 3/FT 4, TFQI, TFQI-FT 3, and TT 4RI were positively associated with the risk of developing MASLD in women. There was a non-linear, inverted U-shaped relationship between TFQI and risk of MASLD in women. Subgroup analyses showed positive associations between FT 3/FT 4, TFQI, TFQI-FT 3, and MASLD. Conclusions:The thyroid hormone sensitivity indices may provide a basis for clinical prevention and management of MASLD in individuals with normal thyroid function. Additionally, FT 3/FT 4 and TFQI-FT 3 may indicate the risk of MASLD in the general population, while TFQI and TT 4RI are more suitable for assessing the risk of MASLD in women.

Objective:To observe the curative effect of a personalized surgical scheme based on scanning source optical coherence tomography (SS-OCT) image features in the treatment of congenital optic disc pit (ODP) with maculopathy (ODP-M).Methods:A prospective interventional cohort study. From September 2019 to May 2024, 15 patients with 15 eyes who were diagnosed with ODP-M by ophthalmology examination in Department of Ophthalmonogy of The First Affiliated Hospital of Zhengzhou University were included in the study. Best corrected visual acuity (BCVA) and SS-OCT were performed in all affected eyes. Standard E word visual acuity chart was used for BCVA examination, which was converted into logarithm of the minimum angle of resolution (logMAR) BCVA for record. The center retinal thickness (CRT) was measured by SS-OCT examination of macular area using VG200D of Henan SVision Imaging Technology Co., LTD. According to the morphological characteristics of ODP and the splitting, edema and detachment of macular region, combined with the degree of pulling of the boundary membrane between the posterior vitreous cortex and macular region, a personalized surgical method was designed. Class I: pars plana vitrectomy combined with macular boundary film stripping, ODP boundary film packing and vitreous cavity gas filling. Class Ⅱ: pars plana vitrectomy combined with non-retained macular boundary film stripping or ODP inner boundary film packing, vitreous cavity gas filling. Class Ⅰ and Class Ⅱ operations were performed in 10 and 5 eyes of 15 eyes, respectively. The postoperative follow-up time was >6 months. Follow-up time was performed with the same equipment before surgery. BCVA changes, CRT reduction rate and complications were observed. BCVA and CRT were compared before and after operation by paired sample t test. Results:There were 15 eyes in 15 cases, 4 eyes in 4 males and 11 eyes in 11 females. The age was (28.87±16.5) years. logMAR BCVA of the affected eye was 0.94±0.51. CRT was (697.80±301.80) μm. At the last follow-up, the logMAR BCVA was 0.53±0.49. CRT was (392.53±167.55) μm. Compared with before operation, BCVA and CRT were significantly improved, and the difference was statistically significant ( t=3.23, 3.25; P=0.006, 0.006). After surgery, transient intraocular hypertension occurred in 2 eyes, and the intraocular pressure returned to normal level after 3 to 7 days without special treatment. Two eyes underwent an unexpected second operation. Among them, one eye underwent Class Ⅰ surgery, the tunnel at ODP was closed after surgery, and there was a small amount of subretinal fluid in the macular area. Class Ⅱ surgery was performed in 1 eye with retinal reattachment. Conclusion:Personalized surgical treatment of ODP-M based on SS-OCT image features can reduce CRT and improve visual acuity.

Bio-mineralization has emerged as a promising strategy to enhance vaccine immunogenicity. This study optimized the calcium phosphate (CaP) mineralization process of foot-and-mouth disease virus-like particles (FMD VLPs) to achieve high mineralization efficiency and scalability. Key parameters, including concentrations of Ca²⁺, HPO₄^2-, NaCl, and VLPs, as well as stirring speed, were systematically optimized. Stability of the scaled-up reaction system and immunogenicity of the mineralized vaccine were evaluated. Optimal conditions [25.50 mmol/L Ca(NO₃)₂, 15 mmol/L Na₂HPO₄, 300 mmol/L NaCl, 0.75 mg/mL VLPs, and 1 500 r/min] yielded CaP-mineralized VLPs (VLPs-CaP) with high mineralization efficiency, uniform morphology, and a favorable particle size. Scaling up the reaction by 25 folds maintained consistent mineralization efficiency and particle characteristics. Immunization in mice demonstrated that VLPs-CaP induced higher titers of specific antibodies and neutralizing antibodies than unmineralized VLPs (P < 0.05). Higher IgG2a/IgG1 ratio and enhanced IFN-γ secretion (P < 0.05) further indicated robust cellular immune responses. We establish a stable and scalable protocol for VLPs-CaP, providing a theoretical and technical foundation for developing high-efficacy VLPs-CaP vaccines.
Vaccines, Virus-Like Particle/immunology* ; Immunogenicity, Vaccine ; Calcium Phosphates/chemistry* ; Foot-and-Mouth Disease Virus ; Biomineralization ; Particle Size ; Animals ; Mice ; Antibodies, Neutralizing/blood* ; Antibodies, Viral/blood* ; Immunity, Cellular

Vaccination is a crucial strategy for the prevention and control of infectious diseases. Virus-like particles (VLPs), composed of structural proteins, have garnered significant attention as a novel type of vaccine due to their excellent safety and immunogenicity. However, similar to most vaccine antigens, VLPs exhibit insufficient thermal stability, which not only restricts the widespread application of vaccines but also increases the risk of vaccine inactivation. This study aims to enhance the stability and shelf life of VLPs derived from type A foot-and-mouth disease virus (FMDV) by employing vacuum freeze-drying technology. The optimal lyoprotectant formulation was determined through single-factor and combinatorial screening. Subsequently, the correlation between the immunogenicity of the freeze-dried vaccine and the content of FMDV VLPs was evaluated via a mouse model. The stability of FMDV VLPs before and after freeze-drying was further assessed by storing them at 4, 25, and 37 ℃ for varying time periods. Results indicated that the lyoprotectant formulation No.1, composed of 7.5% trehalose, 0.1% Tween 80, 50 mmol/L glycine, 1% sodium glutamate, and 3% polyvinylpyrrolidone (PVP), effectively preserved the content of FMDV VLPs during the vacuum freeze-drying process. The immunization trial in mice revealed that the levels of specific antibodies, immunoglobulin G1 (IgG1), interleukin-4 (IL-4), and neutralizing antibodies induced by freeze-dried FMDV VLPs were comparable to those induced by non-freeze-dried FMDV VLPs. The heat treatment results showed that the storage periods of freeze-dried FMDV VLPs at 4, 25, and 37 ℃ were significantly longer than those of non-freeze-dried FMDV VLPs. In conclusion, the selected lyoprotectant formulation effectively improved the stability of FMDV VLPs vaccines. This study provides valuable insights for enhancing the stability of novel subunit vaccines.
Freeze Drying/methods* ; Animals ; Foot-and-Mouth Disease Virus/immunology* ; Mice ; Vaccines, Virus-Like Particle/chemistry* ; Foot-and-Mouth Disease/immunology* ; Vacuum ; Drug Stability ; Mice, Inbred BALB C ; Viral Vaccines/immunology*

Objective : To establish a method for measuring major organic acids in the tricarboxylic acid cycle using a high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS) system, and to investigate the changes in six tricarboxylic acid cycle organic acids(fumaric acid, malic acid, succinic acid, α-ketoglutaric acid, cis-aconitic acid, and citric acid) in the serum, liver, and placenta of mice exposed to di(2-ethylhexyl) phthalate(DEHP) during pregnancy. Methods : The serum, liver and placental samples from pregnant mice were processed and eluted through a Waters ACQUITY UPLC BEH Amide Column(130 Å, 1.7 μm, 2.1 mm × 150 mm) using a gradient elution program. Mobile phase A comprised an aqueous solution of 10 mmol/L ammonium acetate and 5 μmol/L methanephosphonic acid, while mobile phase B consisted of a 90% acetonitrile aqueous solution containing 10 mmol/L ammonium acetate and 5 μmol/L methanephosphonic acid, with a flow rate maintained at 0.35 ml/min. The mass spectrometry detection system utilized an electrospray ionization technique with negative ion mode for multiple reaction monitoring. Results : The correlation coefficients of the standard curves for the six tricarboxylic acid cycle organic acid metabolites were all above 0.996 within the quantitative range. The method's accuracy ranged from 97.14% to 108.26%, with inter-day and intra-day precision relative standard deviation between 1.35% and 6.73%. The matrix effect was between 93.29% and 107.47%, and the extraction recovery rate ranged from 94.82% to 112.57%. Analysis of six tricarboxylic acid cycle organic acids in the liver, serum, and placenta of DEHP-exposed mice during pregnancy showed significant reductions in fumaric acid, malic acid, α-ketoglutaric acid, cis-aconitic acid, and citric acid compared to the control group(P<0.05). Conclusion The HPLC-MS/MS method established in this study for detecting six tricarboxylic acid cycle organic acids in the serum, liver, and placenta of DEHP-exposed pregnant mice is stable, highly sensitive and selective. Prenatal DEHP exposure induced alterations in the levels of tricarboxylic acid(TCA) cycle organic acid metabolites in the liver, serum, and placenta of mice, suggesting that DEHP exposure during pregnancy may interfere with mitochondrial TCA cycle processes. These findings indicate potential value in the diagnosis and treatment of diseases associated with prenatal DEHP exposure.

ObjectiveTo explore the effect of Polygonati Odorati Rhizoma polysaccharides on hyperlipidemia in mice by modulating the gut microbiota. MethodsNinety male C57BL/6J mice were randomized into the following groups （n=15）： control， model， simvastatin， low- （100 mg·kg^-1）， medium- （200 mg·kg^-1）， and high-dose （400 mg·kg^-1） Polygonati Odorati Rhizoma polysaccharides groups. Other groups except the control group were fed with a high-fat diet for the modeling of hyperlipidemia， and drug interventions lasted for 12 weeks. Serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were measured by an automatic biochemical analyzer. The pathological changes in the liver and epididymal fat were observed by hematoxylin-eosin staining， and lipid accumulation in the liver was assessed by oil red O staining. The gut microbiota was analyzed by 16S rRNA gene sequencing. ResultsCompared with the control group， the model group exhibited an increase in body weight （P<0.01）， along with marked elevations in serum levels of TC， TG， and LDL-C （P<0.05，P<0.01）. Furthermore， the model group showcased increase in the liver index and epididymal fat coefficient （P<0.05）， increased liver fat accumulation， enlargement of adipocytes in the epididymal fat， decreases in both alpha and beta diversity of the gut microbiota， and an increase in the relative abundance of Allobaculum （P<0.01）. Compared with the model group， Polygonati Odorati Rhizoma polysaccharides suppressed the increase in body weight （P<0.01）， lowered the serum levels of TC， TG， and LDL-C （P<0.05，P<0.01）， reduced the liver index and epididymal fat coefficient （P<0.05）， alleviated liver fat accumulation， and decreased the size of adipocytes in the epididymal fat. Furthermore， it enhanced the alpha and beta diversity of the gut microbiota in mice， reduced the relative abundance of Allobaculum， Erysipelotrichaceae， and Clostridium （P<0.01）， and increased the relative abundance of Akkermansia and Blautia （P<0.01）. ConclusionPolygonati Odorati Rhizoma polysaccharides can ameliorate hyperlipidemia induced by a high-fat diet in mice by regulating the diversity and composition of the gut microbiota.

Objective : To investigate the protective effect of dimethyl fumarate(DMF) on maternal intrahepatic cholestasis(ICP) during pregnancy induced by di(2-ethylhexyl) phthalate(DEHP) exposure and its mechanism. Methods : Thirty-two 8-week-old female institute of cancer research(ICR) mice were randomly divided into 4 groups: Ctrl group, DEHP group, DMF group and DEHP+DMF group. DEHP and DEHP+DMF groups were treated with DEHP(200 mg/kg) by gavage every morning at 9:00 a.m. DMF and DEHP+DMF groups were treated with DMF(150 mg/kg) from day 13 to day 16 of gestation by gavage. After completion of gavage on day 16 of pregnancy, maternal blood, maternal liver, placenta, and amniotic fluid were collected from pregnant mice after a six-hour abrosia. The body weight of the mother rats and the body weight of the fetus rats were sorted and analyzed; the levels of total bile acid(TBA), alkaline phosphatase(ALP), aspartate aminotransferase/alanine aminotransferase(AST/ALT) in serum and TBA in liver, amniotic fluid and placenta were detected by biochemical analyzer; HE staining was used to observe the pathological changes of liver tissue; Quantitative reverse transcription PCR(RT-qPCR) was used to detect the expression levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-6, IL-1, IL-18 and NOD-like receptor thermal protein domain associated protein 3(NLRP3) in the liver; Western blot was used to detect the expression of the nuclear factor KappaB(NF-κB) and NLRP3. Results : Compared with the control group, the body weight of the DEHP-treated dams and pups decreased(P<0.05); the levels of TBA, ALP, AST/ALT in the serum of dams and the levels of TBA in the liver, amniotic fluid, and placenta of dams increased(P<0.05); the histopathological results showed that liver tissue was damaged, bile ducts were deformed, and there was inflammatory cell infiltration around them; the levels of inflammation-related factors TNF-α, IL-6, IL-1, IL-18 and NLRP3 transcription in maternal liver increased(P<0.05); the expression of NF-κB and NLRP3 protein in maternal liver significantly increased( P<0. 05). Compared with the DEHP group,the body weight of both dams and fetuses significantly increased in DEHP + DMF group( P<0. 05); the levels of TBA,ALP,AST/ALT in the serum of dams and amniotic fluid of fetuses decreased( P<0. 05); the degree of liver lesions was improved; the transcription levels of inflammation-related factors TNF-α,IL-6,IL-1,IL-18 and NLRP3 in maternal liver decreased( P<0. 05); the expression of NF-κB and NLRP3 protein in maternal liver significantly decreased( P<0. 05). Conclusion DMF can effectively protect the DEHP exposure to lead to female ICP,and its mechanism may be through inhibiting the NF-κB/NLRP3 pathway and reducing liver inflammation.

Objective:To explore the correlation between serum ferritin (SF) and risk of lean non-alcoholic fatty liver disease (NAFLD), so as to provide the basis for the prevention and treatment of lean NAFLD.Methods:A total of 7 187 people without NAFLD at baseline who took at least 2 physical examinations in the Health Management Center of the Second Hospital of Dalian Medical University from January 2014 to December 2023 and met the selection criteria were selected as the research subjects, and all the subjects had no NAFLD at baseline. Subjects were divided into four groups according to baseline SF quartiles: 1 797 cases in the first quartile ( Q1) group, 1 797 cases in the second quartile ( Q2) group, 1 797 cases in the third quartile ( Q3) group, and 1 796 cases in the fourth quartile ( Q4) group. The incidence of lean NAFLD in each group were observed. Kaplan-Meier curve was plotted to calculate the cumulative incidence of lean NAFLD which compared by log-rank test. Cox proportional hazard regression model was used to analyze the correlation between SF and new-onset lean NAFLD, Q1, Q2, Q3 and Q4 of SF were taken as continuous variables into the model for trend test.The stability of the results was verified by two item sensitivity analyses. Time-dependent receiver operating characteristic curve (ROC) was plotted to evaluate the predictive value of SF for the onset of lean NAFLD. Results:The cumulative follow-up were 25 076 person-years. There were 230 new cases of lean NAFLD, and the incidence density was 9.172/1 000 person-years. The incidence densities of lean NAFLD in Q1, Q2, Q3 and Q4 groups were 6.915/1 000 person-years, 8.552/1 000 person-years, 9.641/1 000 person-years, 12.003/1 000 person-years, respectively. Kaplan-Meier curve indicated that the incidence of lean NAFLD was increased with the increment of SF, and the difference was statistically significant (log-rank test, χ2=9.92, P=0.019). Cox proportional hazard regression model results showed that the risk of developing lean NAFLD in Q4 group increased by 72.8% ( HR=1.728, 95% confidence interval (95% CI): 1.059 to 2.820) compared with Q1 group. Trend analysis revealed that the risk of lean NAFLD increased by 18.9% for each one-quartile increase of SF( HR=1.189, 95% CI: 1.012 to 1.396). Two sensitivity analyses indicated that the risk of NAFLD in Q4 group was 1.795 times ( HR=1.795, 95% CI: 1.083 to 2.975) or 1.654 times ( HR=1.654, 95% CI: 1.022 to 2.678) higher than that in Q1 group. The area under the curve (95% CI) of SF for predicting the incidence of lean NAFLD at 2-, 3-, 7- and 8-year follow-up based on time-dependent ROC were 0.645 (0.593 to 0.698), 0.652 (0.603 to 0.700), 0.605 (0.539 to 0.672) and 0.716 (0.597 to 0.836), respectively. Conclusion:SF is an independent risk factor for lean NAFLD and has predictive value for the new-onset of lean NAFLD.