Background Large-for-gestational-age (LGA) births are associated with adverse perinatal outcomes and increased risks of offspring obesity, metabolic syndrome, and cardiovascular diseases later in life. Beyond traditional risk factors, exposure to environmental factors, especially fine particulate matter (PM_2.5), before and during pregnancy may contribute to excessive fetal growth; however, the roles of specific chemical constituents and critical exposure windows remain unclear. Objective To examine the associations between maternal exposures to PM_2.5 and its chemical constituents before and during pregnancy and the risk of delivering LGA infants. Methods Singleton pregnancies from the National Free Preconception Health Examination Project between 2010 and 2014 were included. Individual exposures to PM_2.5 and its constituents were estimated for preconception and pregnancy windows using geocoded residential addresses. The associations of single and mixed exposures with LGA risk were analyzed using generalized linear models (GLMs) and qg-computation. Results Exposures to PM_2.5 and its major chemical constituents were significantly associated with an increased LGA risk, with differences in effect magnitude across components. Secondary inorganic aerosols showed the strongest associations. For full-pregnancy exposure, nitrate (OR=1.330, 95%CI: 1.313, 1.347), ammonium (OR=1.279, 95%CI: 1.263, 1.295), and sulfate (OR=1.242, 95%CI: 1.227, 1.257) had larger effects on LGA risk than black carbon and organic matter. Analysis by exposure window indicated that the month preceding conception and the third trimester of pregnancy were critical exposure windows for susceptibility, while the strongest effect was observed for full-pregnancy exposure, suggesting a cumulative effect over time. Mixed exposure analysis further showed that nitrate and sulfate consistently accounted for the main positive contributions across different time windows. Conclusion Maternal exposures to PM_2.5 and its chemical components before and during pregnancy are associated with an elevated LGA risk. Nitrate and sulfate show consistent and strong associations across pregnancy stages, underscoring the importance of component composition and exposure timing in fetal overgrowth.

Objective:To discuss the promotive effect of nerve growth factor(NGF),which is highly expressed in the adipose-derived stem cell(ADSC)-induced Schwann-like cells(SCLCs),on the growth of dorsal root ganglion(DRG)cell processes in the rats,and to clarify its mechanism.Methods:The ADSCs were extracted from the epididymal adipose tissue of the SD rats,and their multidirectional differentiation potential was identified through osteogenic,adipogenic,and chondrogenic induction.The ADSCs were induced to differentiate into the SCLCs,and the expression levels of glial fibrillary acidic protein(GFAP)and S100 calcium-binding protein β(S100β)protein in the ADSCs and SCLCs were detected by immunofluorescence staining and Western blotting methods.The DRG cells were isolated and cultured,and immunofluorescence staining was used to detect the βⅢ-tubulin expression in the DRG cells for identification.The SCLCs were co-cultured with the DRG cells(co-culture group),the single-culture DRG cells were regared as DRG group and toluidine blue staining was used to observe and measure the length of DRG cell processes under the optical microscope in co-culture group and DRG group.Small interfering RNA(siRNA)transfection was used to knock down NGF,and plasmid transfection was used to over-express NGF.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the NGF mRNA expression levels in the cells in various groups;enzyme-linked immunosorbent assay(ELISA)method was used to detect the NGF protein levels in the cell supernatants.The transfected SCLCs were co-cultured with DRG cells and divided into control group,siNC/vector group,NGF knockdown group(si-NGF group),and NGF over-expression group(oe-NGF group).The lengths of DRG cell processes in various groups were observed.Results:The primary ADSCs adhered within 24 h after seeding,with a small number of lipid droplets remaining.After 3 d of culture,the cells were mostly short spindle-shaped,fusiform,or polygonal,growing rapidly in a vortex pattern.After passaging,the cells exhibited a uniform morphology,appearing as long spindles arranged in a fish-school pattern.After 14 d of adipogenic induction,the cell morphology changed from spindle-shaped to flat-round,with translucent lipid droplets forming in the cytoplasm,which were stained red by Oil Red O.After 28 d of osteogenic induction,the cells appeared sand-like with blurred morphology,and calcified nodules were observed,which were stained red by Alizarin Red and deposited in the extracellular matrix.After 28 d of chondrogenic induction in a 3D culture system,millet-sized chondrogenic spheres formed.Frozen sections of the spheres were stained with Alcian Blue,and acidic mucopolysaccharides in the cartilage tissue were stained blue under the microscope.Under the fluorescence microscope,the third-passage purified ADSCs showed positive expression of CD29[fluorescein isothiocy anate(FITC)-labeled green fluorescence]and CD44(Cy3-labeled red fluorescence).The immunofluorescence staining results showed that GFAP was labeled with FITC(green fluorescence),and S100β was labeled with Cy3(red fluorescence).The Western blotting results showed that compared with ADSCs,the expression levels of S100β and GFAP proteins in the SCLCs were increased(P<0.05).The primary DRG cells began to adhere 6 h after conventional culture,and after 3 d,the cell bodies appeared round and bright,with two linear processes extending from them.Under fluorescence microscope,the cells positively expressed the neuron-specific marker βⅢ-tubulin,confirming that the isolated cells were DRG cells.Compared with the ADSCs,the NGF protein expression level in the SCLCs was increased(P<0.05).Compared with DRG group,the length of DRG cell processes in co-culture group was the highest when DRG cells and SCLCs were co-cultured at a 1∶2 ratio(P<0.05).The RT-qPCR results showed that compared with si-NC group,the expression levels of NGF mRNA in the cell supernatant in si-NGF-1,si-NGF-2,and si-NGF-3 groups were significantly decreased(P<0.05),with si-NGF-1 showing the highest knockdown efficiency,which was selected for subsequent experiments.The ELISA results showed that compared with si-NC group,the NGF levels in the cell supernatant of si-NGF-1,si-NGF-2,and si-NGF-3 groups were decreased(P<0.05).Compared with Vector group,the expression level of NGF mRNA and NGF protein level in the supernatant in oe-NGF group were increased(P<0.05).Compared with control group and siNC/vector group,the length of DRG cell processes in si-NGF group was decreased(P<0.05),while the length of DRG cell processes in oe-NGF group was increased(P<0.05).Conclusion:ADSCs can be directionally differentiated into SCLCs,and the differentiated cells highly express NGF.Knockdown or overexpression of NGF can affect the growth of DRG cell processes.

Nitrogen oxides(NOx=NO+NO2)are important precursors of ozone(O3),and NOx and its oxides together constitute reactive nitrogen oxides(NOy)in the atmosphere.A comprehensive understanding of the total NOy level in the atmosphere is of great significance for a deeper understanding of the atmospheric nitrogen cycle and oxidation,as well as for formulating strategies for air pollution prevention and control.In this work,a thermal decomposition-broadband cavity enhanced absorption spectroscopy(TD-BBCEAS)technique for online measurement of total NOy in the atmosphere was developed.With this method,the NOy was efficiently converted into NO2,and the total NOy concentration in the atmosphere was indirectly obtained by measuring NO2.Focusing on the key factors affecting the measurement of total NOy,the influence of NO titration efficiency and other NOy component TD efficiency on measurement accuracy was emphasized.By changing the oxygen(O2)flow rate through the mercury lamp to alter the O3 concentration for titrating NO,the conversion efficiency of NO was evaluated.At O2 flow rate of 6 mL/min,the conversion efficiency of NO was greater than 99%.TD efficiency testing and analysis on NO2,peroxyacetyl nitrate(PAN),nitric acid(HNO3),and nitrous acid(HONO),which account for a large proportion of atmospheric NOy components,was carried out using 680℃as the optimal TD temperature for efficient conversion of NOy.With NO and HONO sample gases as typical verification gases,the conversion efficiency of NOy and the accuracy of NOy measurement by TD-BBCEAS system were verified by switching the on and off modes of mercury lamp and TD device.At integration time of 60 s,the detection limit of the system for NOy was 2.83×1010 molecules/cm3(60 s,2σ).A comparative measurement of actual atmospheric NOy was conducted between the TD-BBCEAS system and the NOy analyzer.The observation results showed a correlation coefficient(R2)of 0.98 and a slope of 0.93,further verifying the feasibility and accuracy of applying the TD-BBCEAS system to measurement of total NOy.

Objective To explore the mechanism underlying the role of disulfidptosis-related genes(DRGs)in the disease progression of metabolically associated fatty liver disease(MAFLD)based on bioinformatics.Methods In this study,the GEO database was utilized to screen for eligible MAFLD expression data,conduct differential gene analysis,and identify DRGs through consistent clustering to subtype MAFLD patients.The immune infiltration status among subtypes was further evaluated,and the infiltration of immune cells was analyzed using the CIBERSORT algorithm.The gene modules related to the disease were selected through weighted gene co-expression network analysis(WGCNA).Subsequently,a diagnostic model was constructed based on DRGs using machine learning models,and the performance of the model was verified.Finally,the stability of DRGs among different subtypes was evaluated using an external dataset,and the significance of the results was analyzed using statistical tests.Results Through the analysis of the dataset GSE31803,six disulfide death genes,namely,SLC3A2,NCKAP1,CYFIP1,FLNA,MYL6 and MYH10,which were closely related to the clinical characteristics of MAFLD,were screened out.MAFLD patients were classified into two subtypes,with subtype 1 having a higher level of immune cell infiltration.Key gene modules were identified through WGCNA.Through machine learning screening,the support vector machine(SVM)model was determined as the optimal classification model.External validation confirmed the stability and effectiveness of the key genes in different subtypes of MAFLD.Conclusion Based on DRGs,two highly heterogeneous subtypes of MAFLD were identified,which exhibited significant differences in clinical characteristics,biological processes and immune status,indicating that DRGs play a crucial role in the occurrence and development of MAFLD.

Azvudine and nirmatrelvir/ritonavir (Paxlovid) are recommended for COVID-19 treatment in China, but their safety and efficacy in the elderly population are not fully known. In this multicenter, retrospective, cohort study, we identified 5131 elderly hospitalized COVID-19 patients from 32,864 COVID-19 patients admitted to nine hospitals in Henan Province, China, from December 5, 2022, to January 31, 2023. The primary outcome was all-cause death, and the secondary outcome was composite disease progression. Propensity score matching (PSM) was performed to control for confounding factors, including demographics, vaccination status, comorbidities, and laboratory tests. After 2:1 PSM, 1786 elderly patients receiving azvudine and 893 elderly patients receiving Paxlovid were included. Kaplan-Meier and Cox regression analyses revealed that compared with Paxlovid group, azvudine could significantly reduce the risk of all-cause death (log-rank P = 0.002; HR: 0.71, 95% CI: 0.573-0.883, P = 0.002), but there was no difference in composite disease progression (log-rank P = 0.52; HR: 1.05, 95% CI: 0.877-1.260, P = 0.588). Four sensitivity analyses verified the robustness of above results. Subgroup analysis suggested that a greater benefit of azvudine over Paxlovid was observed in elderly patients with primary malignant tumors (P for interaction = 0.005, HR: 0.32, 95% CI: 0.18-0.57) compared to patients without primary malignant tumors. Safety analysis revealed that azvudine treatment had a lower incidence of adverse events and higher lymphocyte levels than Paxlovid treatment. In conclusion, azvudine treatment is not inferior to Paxlovid treatment in terms of all-cause death, composite disease progression and adverse events in elderly hospitalized COVID-19 patients.

The advancement of surgical techniques enables effective treatment for many patients with oral and maxillofacial tumors.How-ever,post-surgery problems such as chewing,swallowing and speech difficulty may arise due to the defects in speech organs and inade-quate compensatory function of tissue flap repair.Speech disorders,in particular,isolate patients by making it difficult for them to com-municate with others,not only impact their quality of life but also potentially lead to psychological problems and social interaction disor-ders.Although the decline in life quality and other related issues caused by speech dysfunction due to surgery and radiotherapy or chemo-therapy have been widely recognized,there is currently no standardized and universally applicable assessment method and standardized re-habilitation treatment management guideline or consensus for speech disorders following oral and maxillofacial tumor surgery at home and abroad.Based on previous clinical practice,combined with the characteristics of speech disorders in patients after oral and maxillofacial tumor surgery,the clinical experience of the experts in maxillofacial tumor surgery and rehabilitation and the relevant domestic and foreign literature,relevant experts organized discussions and modifications,reach a consensus on core content such as the assessment of speech disorders and the implementation plan for early rehabilitation treatment management,providing a reference for clinical practice,in order to improve patients'speech-related life quality and enhance the assessment and rehabilitation treatment techniques for speech disorders after oral and maxillofacial tumor surgery.

Artificial intelligence (AI) integrated with time-lapse (TL) imaging for embryo selection significantly minimizes subjectivity and workload in traditional methods, marking a pivotal advancement in the realm of assisted reproductive technology. This review comprehensively summarizes the representative studies conducted in recent years within these domains and delves into the application of AI combined with TL imaging for embryo selection from three perspectives: data selection, model selection, and model evaluation. While AI research has yet to fully achieve automated embryo selection, it has already commenced assisting embryologists in annotating and selecting embryos to a considerable extent, thereby reducing subjective discrepancies and easing the workload. Existing software for oocyte quality scoring, embryo ploidy prediction, and transfer outcome forecasting has exhibited promising performance in studies. However, there remains an ongoing need for the development of high-quality datasets and the conduct of prospective, multicenter studies with large sample sizes across diverse devices. The evolution of AI combined with TL imaging in the field of embryo selection merits heightened attention from both clinicians and embryologists.

Objective To investigate the effects of long non-coding RNA FGD5-AS1 on the proliferation,migration,and invasion of pituitary adenoma(PA)cells,and to analyze its potential mechanism of action.Methods Human PA cell lines HPAs,RC-4BC,HP75,and human astrocyte cell line NHA were cultured in vitro.The expression levels of FGD5-AS1 and miR-15a in the above cell lines were detected by RT-PCR.HP75 cells in the logarithmic growth phase were randomly divided into the silencing group and the negative control group.The silencing group was transfected with shRNA-FGD5-AS1,while the negative control group was transfected with shRNA-NC.The expression levels of FGD5-AS1 and miR-15a in the two groups of cells were detected by RT-PCR.The proliferation,migration and invasion abilities of the two groups of cells were determined by CCK-8 assay,wound healing assay,and Transwell assay.The expression of proteins related to the Wnt/β-catenin signaling pathway in the two groups of cells was detected by Western blot.The targeting relationship between FGD5-AS1 and miR-15a was verified by dual-luciferase reporter gene assay.Results Compared with the NHA cell,the expression level of FGD5-AS1 was significantly increased in the HPAs,RC-4BC,and HP75 cells((P<0.05),whereas the expression level of miR-15a was significantly decreased(P<0.05).Compared with the negative control group,the expression level of FGD5-AS1 was decreased(P<0.05),the expression level of miR-15a was increased(P<0.05),the OD value was decreased(P<0.05),the migration and invasion abilities of cells were reduced(P<0.05),and the expression of Wnt3a and β-catenin proteins was decreased in the silencing group of HP75 cells(P<0.05).FGD5-AS1 could specifically bind to miR-15a,leading to a decrease in cell luciferase activity(P<0.05).Conclusion FGD5-AS1 is overexpressed in PA cells,and silencing FGD5-AS1 can inhibit the proliferation,migration,and invasion of PA cells,and the mechanism is related to its targeted regulation of miR-15a.

Objective To compare the effect of small optical zone orthokeratology lenses(OK lenses)and repeated low-level red-light(RLRL)therapy in controlling myopia progression for adolescents,and the therapeutic effectiveness of RLRL is evaluated.Methods A retrospective analysis was conducted on the clinical data of 80 adolescent myopic patients in the First Affiliated Hospital of Army Medical University.The patients were divided into the RLRL group and the OK lenses group according to different intervention methods,with 40 cases in each group.Patients in the RLRL group received RLRL therapy combined with single-vision spectacles,and patients in the OK lenses group were treated with OK lenses.The changes of spherical equivalent(SE),axial length and subfoveal choroidal thickness(SFCT)1,3,6,and 12 months after treatment compared with the baseline,and color vision of patients were assessed.Based on the mean baseline axial length of the RLRL group,the patients in this group were subdivided into the short axial group and the long axial group,and the changes of the axial length and SFCT were further analyzed.Results The diopter 1,3,6,and 12 months after treatment in the RLRL group were not significantly different from the baseline(P>0.05).Axial lengths of patients in the RLRL group progressively shortened after treatment and returned close to the baseline 12 months after treatment.In contrast,axial lengths of patients in the OK lens continued to grow within 12 months after treatment;the axial lengths at each time point after treatment of patients in the two groups were significantly different from the baseline(P<0.05).The changes of axial length of patients in the RLRL group at each time point after treatment were significantly smaller than those in the OK lenses group(P<0.05).The SFCT changes of patients in the RLRL group at each time point after treatment were all greater than those in the OK lenses group(P<0.05).The SFCT at each time point after treatment in the RLRL group were significantly different from the baseline(P<0.05),whereas the SFCT at each time point after treatment in the OK lenses group were not significantly different from the baseline(P>0.05).The changes of axial length at each time point after treatment of patients in the long axial group were all greater than those in the short axial group(P<0.05);the SFCT changes 6 months after treatment of patients in the long axial group was greater than that in the short axial group(P<0.05);the SFCT at each time point after treatment of patients in the two groups were signifi-cantly different from the baseline(P<0.05).Color vision tests revealed no abnormities after treatment in the RLRL group and the OK lenses group.Conclusion RLRL therapy is effective in controlling myopia progression and demonstrates superior axial length control compared to orthokeratology lenses.

Objective:This study aimed to analyze the prognostic risk factors for hepatoid adenocarcinoma of the stomach (HAS) and construct two nomogram-based clinical prediction models to predict overall survival (OS) and recurrence-free survival (RFS) in patients with HAS.Methods:Data were retrospectively collected from 82 patients (64 males, 18 females; mean age 60.3 ± 9.4 years) who underwent radical gastrectomy and were pathologically diagnosed with gastric hepatoid adenocarcinoma at the First Medical Center of the PLA General Hospital between February 2006 and September 2023. Statistical analyses were conducted using SPSS 25.0 and R 4.3.2. Survival analyses were performed using the Kaplan-Meier method, and univariate analyses were used to identify clinical and pathological factors associated with prognosis. Variables with P<0.05 in the univariate analysis were included in multivariate Cox regression models to identify independent risk factors for OS and RFS. These factors were incorporated into the prediction models to construct nomograms. The discriminatory power of the models was assessed using the area under the curve (AUC) of receiver operating characteristic (ROC) analyses, while calibration curves, decision curve analysis (DCA), and comparisons with the 8th edition of the TNM staging system of the American Joint Committee on Cancer (AJCC) were employed to evaluate model performance. Results:Among the 82 patients, 36 (43.9%) exhibited vascular infiltration, 61 (74.4%) had nerve infiltration, and lymph node metastasis was observed in 60 cases (73.2%). Pathological stages I, II, III, and IV were distributed as 11 (13.4%), 26 (31.7%), 44 (53.7%), and 1 (1.2%) cases, respectively. Inflammatory markers included neutrophil-to-lymphocyte ratio (NLR) ≥ 4.33 in 22 cases (26.8%), platelet-to-lymphocyte ratio (PLR) ≥ 142.2 in 50 cases (61.0%), monocyte-to-lymphocyte ratio (MLR) ≥ 0.411 in 22 cases (26.8%), α-fetoprotein (AFP) ≥ 2.48 μg/L in 64 cases (78.0%), and C-reactive protein (CRP) ≥ 7.506 mg/L in 12 cases (14.6%). Among the 82 patients, 3 cases (3.6%) were lost to follow-up. The median follow-up time was 52 (range: 8–147) months, with a median OS of 61(2–147) months. The 1-year and 3-year OS rates were 78.5% and 58.5%, respectively, while the 1-year and 3-year RFS rates were 77.3% and 60.3%, respectively. Multivariate analysis identified several independent risk factors influencing OS in patients with HAS: advanced pathological stage, MLR ≥ 0.411, AFP ≥ 2.545 μg/L, and CRP ≥ 7.51 mg/L. The hazard ratios (HRs) and 95% confidence intervals (CIs) were as follows: 5.218 (1.230–22.143), 2.610 (1.287–5.294), 2.950 (1.013–8.589), and 2.594 (1.145–5.877), respectively (all P < 0.05). For RFS, advanced pathological stage, PLR ≥ 152.0, and MLR ≥ 0.411 were independent risk factors, with HRs (95% CIs) of 4.735 (1.080–20.760), 3.759 (1.259–11.226), and 2.714 (1.218–6.048), respectively (all P < 0.05). The AUC values for OS prediction at 1 year, 3 years, and 5 years were 0.7765, 0.7525, and 0.7702, respectively. For RFS, the AUC values were 0.7304, 0.8137, and 0.8307 at 1 year, 3 years, and 5 years, respectively. The calibration curves demonstrated strong agreement between nomogram- predicted outcomes and observed survival data. DCA indicated that both TNM staging and the nomogram-based clinical prediction models provided a net positive benefit in predicting OS and RFS in HAS patients, with the nomogram model demonstrating superior performance. Conclusion:The nomogram-based clinical prediction models developed in this study demonstrated robust performance in predicting long-term OS and RFS in patients with HAS.