Objective: To explore the relationship between serum homocysteine (Hcy), interleukin-5 (IL-5), folate and core symptoms in children with autism spectrum disorders, so as to provide potential biomarkers for early diagnosis and intervention of diseases. Methods: A total of 106 children with autism spectrum disorders and 106 healthy children with matched sex and age in Lu an People s Hospital were enrolled as autism group and healthy group between May 2020 to December 2023. On the day of admission, levels of serum Hcy, IL-5 and folate were detected. The core symptoms in autism group were evaluated by Autism Behavior Checklist (ABC), Wechsler Preschool and Primary Scale of Intelligence-fourth edition(WPPSI-IV), Childhood Autism Rating Scale (CARS) and Social Responsiveness Scale (SRS). The levels of serum Hcy, IL-5 and folate in the two groups were compared by t- test. The relationship between serum Hcy, IL-5, folate and core symptoms in children with autism spectrum disorders was determined by Pearson correlation analysis. Results: The levels of serum Hcy and IL-5 in autism group were (7.48±0.32) μmol/L and (345.77±32.51) pg/mL, higher than those in healthy group [(6.11±0.54) μmol/L, (274.04±25.17) pg/mL], while folate level was lower than that in healthy group [(15.24±3.47) ng/mL, (22.51±4.69) ng/mL], the differences were statistically significant ( t =22.47, 17.96, 12.83, all P < 0.05 ). In autism group, levels of serum Hcy and IL-5 were positively correlated with scores of ABC, CARS and SRS ( r =0.29, 0.53 , 0.54; 0.45, 0.41, 0.50), while negatively correlated with WPPSI-IV score ( r =-0.28, -0.26)(all P <0.05). The folate level was negatively correlated with scores of ABC, CARS and SRS ( r =-0.55, -0.40, -0.25), while positively correlated with WPPSI-IV score ( r =0.41) (all P <0.05). Conclusion Children with ASD show elevated serum Hcy and IL-5 alongside decreased folate,and three markers correlate with core symptoms and intellectual level.

As the biggest tissue of human body, skin is the first barrier of resisting external aggression. Collagen is one of important parts of the skin, which could not only affect the aesthetics of skin, but also influence the health and normal function of skin. It is the great significance to find ways that could inhibit the loss of collagen. The mechanisms of the collagen degradation in skin are complex and multifaceted. Natural bioactive products have unique advantages in treating the loss of collagen, which have multi-targets and mechanisms. In this review, the mechanisms of skin collagen degradation are discussed, and the research progress of natural bioactive products in resisting skin aging through promoting collagen synthesis are reviewed, in order to provide references for futural research.

AIM: To analyze the prevalence, severity, types, and correction of astigmatism in children, and provide scientific evidences for the prevention and treatment of refractive errors.METHODS: This cross-sectional study included 29 153 children aged 6-12 years from Xi'an and Lantian County, Shaanxi Province, China. Visual acuity and non-cycloplegic refraction were measured. Astigmatism was defined as an absolute cylindrical power ≥0.5 D in the right eye. Differences in astigmatism severity, type distribution, and refractive correction were analyzed across age, gender, and region.RESULTS:The prevalence of astigmatism increased with age, peaking at 11 years old(62.88%). Boys(57.10%)had a higher prevalence than girls(54.86%), and the municipal areas(58.29%)had a higher prevalence than county areas(51.75%). Mild astigmatism was the most common(63.82%), with moderate astigmatism increasing with age. The highest prevalence of high astigmatism was observed in 11-years-old children(9.68%). Compound myopic astigmatism(59.28%)and mixed astigmatism(25.16%)were the most frequent types. With increasing age, compound myopic astigmatism increased, while simple myopic, simple hyperopic, and compound hyperopic astigmatism decreased. Mixed astigmatism increased from ages 6 to 7, but declined from ages 7 to 12. For astigmatic axis types, with-the-rule astigmatism was the most prevalent(81.06%)and increased with age, peaking at 11 years(85.74%). Against-the-rule astigmatism showed a declining trend, while oblique astigmatism remained relatively stable. Distribution differences in astigmatism types and axes by gender and region were observed. Significant differences in astigmatism severity, types, and axis types across different ages, genders, and regions were observed(all P<0.05). The overall refractive correction rate for children with astigmatism was only 40.18%.CONCLUSION: The overall prevalence of astigmatism among children aged 6-12 years in Shaanxi Province was 56.02%, with higher prevalence observed in boys and in municipal areas. Age, gender, and region significantly influenced the prevalence of astigmatism. Notably, less than half of the children with astigmatism received refractive correction, highlighting the need for increased attention from parents and relevant authorities.

Purpose: This study assessed the performance of the ultrasound-guided attenuation parameter (UGAP) in diagnosing and grading hepatic steatosis in patients with metabolic dysfunctionassociated steatotic liver disease (MASLD). Magnetic resonance imaging proton density fat fraction (MRI-PDFF) served as the reference standard. Methods: Patients with hepatic steatosis were enrolled in this prospective study and underwent UGAP measurements. MRI-PDFF values of ≥5%, ≥15%, and ≥25% were used as references for the diagnosis of steatosis grades ≥S1, ≥S2, and S3, respectively. Spearman correlation coefficients and area under the receiver operating characteristic curves (AUCs) were calculated. Results: Between July 2023 and June 2024, the study included 88 patients (median age, 40 years; interquartile range [IQR], 36 to 46 years), of whom 54.5% (48/88) were men and 45.5% (40/88) were women. Steatosis grades exhibited the following distribution: 22.7% (20/88) had S0, 50.0% (44/88) had S1, 21.6% (19/88) had S2, and 5.7% (5/88) had S3. The success rate for UGAP measurements was 100%. The median UGAP value was 0.74 dB/cm/MHz (IQR, 0.65 to 0.82 dB/ cm/MHz), and UGAP values were positively correlated with MRI-PDFF (r=0.77, P<0.001). The AUCs of UGAP for the diagnoses of ≥S1, ≥S2, and S3 steatosis were 0.91, 0.90, and 0.88, respectively. In the subgroup analysis, 98.4% (60/61) of patients had valid controlled attenuation parameter (CAP) values. UGAP measurements were positively correlated with CAP values (r=0.65, P<0.001). Conclusion Using MRI-PDFF as the reference standard, UGAP demonstrates good diagnostic performance in the detection and grading of hepatic steatosis in patients with MASLD.

Metabolic associated fatty liver disease （MAFLD） is a liver disease associated with metabolic disorders， and it is characterized by excessive fat deposition in hepatocytes and is closely associated with insulin resistance and genetic susceptibility. Aging is an important factor in the progression of MAFLD and is positively correlated with the mortality rate of patients with MAFLD. The pathophysiological mechanisms of MAFLD involve lipid metabolism disorders， insulin resistance， inflammation， and oxidative stress， and aging exacerbates the pathological process of MAFLD by further affecting these key mechanisms. Cell senescence is an important factor in organismal aging， and therapeutic strategies targeting senescent cells can reduce the number of senescent cells or inhibit the inflammatory factors secreted by such cells， thereby helping to slow down the progression of MAFLD. In addition， the screening of novel regulatory factors provides new targets for the development of new drugs for MAFLD treatment. Although several anti-aging therapies have entered clinical trials， further studies are needed to validate the specificity and potential liver damage of these therapies due to the complex mechanisms of aging on the liver. Transforming multisystem metabolic dysfunction therapies for MAFLD into specialized therapies for aging may provide new ideas for MAFLD drug development.

Objective To investigate the association between gastroesophageal reflux disease(GERD)and the risk of incident chronic obstructive pulmonary disease(COPD)and explore potential effect modifiers influencing this association.Methods Clinical data from 476 175 participants in the UK Biobank(2006-2010)were collected.A Cox proportional hazards model was used to assess the relationship between GERD and the risk of incident COPD.Subgroup analyses were conducted to examine potential modifiers of the primary findings.Results A total of 11 587(2.43%)new COPD cases were diagnosed.The Cox proportional hazards model revealed that GERD was associated with an increased risk of incident COPD(HR=1.59,95%CI=1.46-1.74,P<0.001).GERD was linked to a higher risk of incident COPD in individuals aged<60 years(P<0.001)and non-smokers(P=0.011).No association was observed between GERD and the risk of incident COPD in current smokers with a daily cigarette consumption<10 cigarettes(P=0.261).Conclusion GERD may increase the risk of incident COPD.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Gastroesophageal Reflux/epidemiology* ; Middle Aged ; Proportional Hazards Models ; Incidence ; Male ; Risk Factors ; Female ; Aged

ObjectiveTo investigate the application of the novel inflammatory factor adsorption column CA280 combined with low-dose plasma exchange （LPE） in patients with acute-on-chronic liver failure （ACLF）. MethodsA prospective cohort study was designed， and a total of 93 ACLF patients who were admitted to The Ninth Hospital of Nanchang from June 2023 to January 2025 were enrolled and randomly divided into DPMAS+LPE group with 50 patients and CA280+LPE group with 43 patients. In addition to comprehensive medical treatment， the patients in the DPMAS+LPE group received DPMAS and LPE treatment， and those in the CA280+LPE group received CA280 and LPE treatment. The two groups were observed in terms of routine blood test results， liver function parameters， renal function markers， electrolytes， coagulation function parameters， cytokines， adverse events， and 28-day prognosis before surgery （baseline）， during surgery （DPMAS or CA280）， and after surgery （after sequential LPE treatment）. The paired t-test was used for comparison of normally distributed continuous data before and after treatment within each group， and the independent-samples t test was used for comparison between groups； the Wilcoxon signed-rank test was used for comparison of non-normally distributed continuous data before and after treatment within each group， and the Mann-Whitney U test was used for comparison between groups. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups， and the Spearman test was used for correlation analysis. ResultsAfter CA280 treatment， the ACLF patients had significant reductions in the levels of cytokines （IL-6， IL-8， IL-10， TNF-α， and IFN-γ）， liver function parameters （ALT， AST， ALP， TBil， DBil， Alb， and glutathione reductase）， and the renal function marker urea nitrogen （all P<0.05）， and in terms of coagulation function parameters， there were significant increases in prothrombin time， activated partial thromboplastin time （APTT）， thrombin time， and international normalized ratio （INR） and significant reductions in prothrombin activity （PTA） and fibrinogen （FIB） （all P<0.05）. Compared with the DPMAS+LPE group， the CA280+LPE group showed better improvements in the serum cytokines IL-8 （Z=-2.63， P=0.009）， IL-10 （Z=-3.94， P<0.001）， and TNF-α （Z=-1.53， P=0.023）， and the two artificial liver support systems had a similar effect in improving liver function （ALT， AST， GGT， GR， TBil， and DBil） （all P >0.05）， but the CA280+LPE group showed a significantly greater reduction in Alb （Z=-2.08， P=0.037）. CA280+LPE was more effective in reducing uric acid （Z=-2.97， P=0.003）. Compared with DPMAS+LPE， CA280+LPE treatment resulted in a significant reduction in INR （Z=-4.01， P<0.001）， a significant increase in APTT （Z=-2.53， P=0.011）， and significant greater increases in PTA （Z=-6.28， P<0.001） and FIB （Z=-3.93， P<0.001）. There were no significant differences in the incidence rates of adverse reactions and the rate of improvement at discharge between the two groups （all P>0.05）. The Spearman correlation analysis showed that IL-6 was significantly correlated with WBC （r=0.22， P=0.042）， TBil （r=0.29， P=0.005）， and FIB （r=-0.33， P=0.003）； IL-8 was positively correlated with APTT （r=0.37， P<0.001） and INR （r=0.25， P=0.013）； TNF-α was significantly correlated with WBC （r=0.40， P<0.001） and TBil （r=0.34， P<0.001）. ConclusionCompared with DPMAS， CA280 combined with LPE can effectively clear proinflammatory cytokines and improve liver function in ACLF patients， but it has a certain impact on Alb and coagulation function. This regimen provides a new option for the individualized treatment of ACLF and can improve the short-term prognosis of patients， but further studies are needed to verify its long-term efficacy.

Objective To preliminarily explore the potential efficacy of Xuesaitong Soft Capsule(XST)against post-stroke depression(PSD),and to investigate the material basis of XST's anti-PSD effect based on the metabolomics results to analyze its related pharmacokinetic(PK)characteristics and further analyze the pharmacodynamic(PD)equation of representative ingredients.Methods The initial evaluation of drug effica-cy was conducted by detecting the depressive-like behavior and neurotransmitter levels in rats.The Pearson correlation analysis was employed to analyze the correlation between the main metabolites regulated by XST and the saponin components entering the bloodstream.At various time points after drug administration,the blood concentration of ginsenoside Re and the concentration of norepinephrine(NE)in the serum of PSD rats were measured,and the compartment model was fitted accordingly.Furthermore,the liquid chromatography-mass spectrometry was utilized to determine the content of ginsenoside Re in the liver,spleen,kidney,prefron-tal cortex,hippocampus and striatum of PSD rats.Results Ginsenoside Re showed the optimal correlation by the Pearson correlation analysis.Based on its pharmacokinetic parameters,the pharmacodynamic equation with NE was E=160.462 × Ce/(38.663+Ce).The contents of ginsenoside Re in the liver,spleen,kidney,prefron-tal cortex,hippocampus and striatum of rats were(17.23+11.90),(19.05+5.67),(1.95+0.79),(70.13+6.75),(57.03+3.11),and(72.45+5.45)ng/g,respectively.Conclusion XST could improve the depressive-like behaviors in PSD rats by regulating the expression levels of neurotransmitter NE and 5-HT.Ginsenoside Re may be the pharmacodynamical material foundation for XST's preventative treatment of PSD.

Objective To investigate the synergistic therapeutic effects of HER2 antibody-drug conjugate(HER2-ADC)combined with anti-PD-1 antibody(anti-PD-1)on HER2-expressing bladder cancer and elucidate its regulatory mechanisms on the tumor immune microenvironment.Methods Orthotopic tumor models were established in 40 female C57BL/6 mice(6～8 weeks old,body mass 18～22 g)using MB49 bladder cancer cells overexpressing human HER2.When tumors reached 100 mm3,the mice were randomized into(n=10)control(intraperitoneal injection of 1.0 mL PBS),anti-PD-1(200 μg per mouse every 3 d),HER2-ADC(2.5 mg/kg once weekly),and combination groups(same regimens as above monotherapy).Tumor volume and body mass were measured every 3 d during 28-day treatment.Tumor growth kinetics and survival rates were analyzed.Post-treatment survival was monitored until natural death to determine median survival time(n=5).At day 28,blood and tumor samples(n=5)were collected to detect myeloid-derived suppressor cells(MDSCs;CD11b?Gr1?)and regulatory T cells(Tregs;CD4?CD25?FOXP3?)with flow cytometry,tumor-infiltrating CD3?T,CD8?T,and FOXP3?T cells with immunohistochemical assasy,and liver/kidney functions[alanine aminotransferase(ALT),aspartate aminotransferase(AST),blood urea nitrogen(BUN),creatinine(CRE)]and tissue damage indicators[lactate dehydrogenase isoenzyme(LDH-L)].Results In 28 d after treatment,the combination group obtained significantly smallest tumor volume than the control group and the 2 monotherapy groups(all P<0.01).The longest median survival was observed in the combination group(65 d,P<0.01),followed by the HER2-ADC group(55 d),anti-PD-1 group(53 d)and control group(41 d).After 28 d of treatment,the combination group exhibited obviously the smallest peripheral proportions of MDSCs/Tregs,most tumor-infiltrating CD3?T/CD8?T cells,and less FOXP3?T cells when compared with the 2 monotherapy groups and control group(all P<0.05).While,the 2 monotherapy groups had smaller MDSCs/Tregs proportions than the control group(P<0.05).No significant differences were observed among the 4 groups in serum ALT,AST,BUN,CRE,or LDH-L levels,and all of them were within normal ranges.Conclusion HER2-ADC combined with anti-PD-1 suppresses the growth of orthotopic bladder tumor,probably through their synergic effects on down-regulating MDSCs/Treg and enhancing CD8?T cell infiltration.

Objective To investigate the mechanism by which peripubertal exposure to di-2-ethylhexyl phthalate(DEHP)induces reproductive injury in adult male mice through impairment of Sertoli cell function and the blood-testis barrier.Methods A total of 180 male C57BL/6J mice(3 weeks old)were randomly divided into corn oil group(control group),and 5,25,125,250 and 500 mg/kg DEHP exposure groups.All groups received daily oral gavage for 5 consecutive weeks.Ten mice from each group were sacrificed for first material collection when they were 9 weeks old.The remaining F0 generation mice were mated with unexposed adult female mice at a male-to-female ratio of 1∶2 at 14 weeks of age for a period of 2 weeks.The second material collection was completed at 16 weeks of age,with 20 mice taken from each group.A computer-assisted analysis system was used to detect sperm density and motility in 9-week-old and 16-week-old male mice.The average birth body weight of F1 generation pups,survival rate of pups at 4 d after birth per litter,number of pups per litter,and male-to-female sex ratio within the litter were recorded.ELISA was used to detect hormone levels in the serum.Sperm abnormalities were observed using eosin staining.HE staining was used to observe pathological changes in testicular tissue.Immunofluorescence assay was utilized to detect the protein expression of tight junction protein 1(zonula occludens-1,ZO-1)and gap junction protein 43(connexin43,Cx43)related to the blood-testis barrier in testicular tissue,as well as the protein expression of apoptosis-related molecule Cleaved-Caspase3.Immunohistochemistry was used to detect the expression of Sertoli cell marker SOX9 protein in testicular tissue.TUNEL was used to detect apoptosis in testicular tissue.Comparative toxicogenomics database(CTD)was used to screen for mono-2-ethylhexyl phthalate(MEHP)induced reproductive damage-associated genes and combined with GO/KEGG and Reactome enrichment analysis to predict possible signaling pathways.An in vitro exposure model was established by treating TM4 cells with MEHP at concentrations of 0,50,100,200 and 400 μmol/L,respectively.CCK-8 assay,flow cytometry and Western blotting were applied to detect the cell viability,apoptosis,and protein expression of apoptosis-related proteins B-cell lymphoma 2(Bcl-2)and Bcl-2-associated X protein(Bax),and blood-testis barrier-related proteins ZO-1 and Cx43.Results Compared with the control group,the pregnancy rate was decreased from 80.0%to 52.5%,and the total number of pups was decreased from 212 to 125 in the female mice mating with the male from the 500 mg/kg group.Compared with the control group,the sperm density and motility were significantly reduced,and the total rate of sperm abnormalities was obviously increased in the 9-week-old DEHP-exposed mice(P<0.05),and even in the 16-week-old mice,the sperm motility was still in a dose-dependent downward trend(P<0.05).In the 25,125,250 and 500 mg/kg DEHP exposure groups,the thickness of the seminiferous epithelium was obviously decreased,with more cellular vacuolization and notable epithelial atrophy and degeneration.Cell apoptosis in the testicular tissue was enhanced,while the expression of ZO-1 and Cx43 were decreased in the 250 and 500 mg/kg exposure groups.The levels of androgen-binding protein,gonadotropin-releasing hormone,and testosterone in the serum were decreased in a dose-dependent manner(P<0.05),while those of luteinizing hormone and follicle-stimulating hormone showed a dose-dependent increase(P<0.05).Bioinformatics analysis showed that 153 genes related to male system diseases were screened out by CTD for MEHP.GO enrichment,KEGG pathway,and Reactome enrichment analyses displayed that the apoptosis signaling pathway was significantly enriched.CCK-8 assay showed that TM4 cell viability was decreased in a dose-dependent manner after MEHP treatment when compared with the control group(P<0.05).Western blotting indicated that MEHP treatment reduced the expression levels of Bcl-2,ZO-1 and Cx43(P<0.05),and enhanced that of Bax in comparison with the control group(P<0.05).Conclusion Peripubertal DEHP exposure may lead to reduced sperm quality and reproductive damage in adult male mice by disrupting the blood-testis barrier and activating Sertoli cell apoptosis.