Background Intrauterine growth restriction (IUGR) is closely associated with placental dysfunction. However, the effects of preconception co-exposure to β-cypermethrin (β-CYP) and emamectin benzoate (EMB) on fetal growth and placental function remain unclear. Objective To investigate the effects of prenatal exposure to β-CYP and EMB on embryonic development in female rats and to elucidate the mechanisms by which these substances cause IUGR from the perspectives of placental structure, progesterone synthesis, and mitochondrial autophagy. Methods Forty-eight specific pathogen-free (SPF) adult female Sprague-Dawley (SD) rats were randomly assigned to a control group, a β-CYP group, an EMB group, and a co-exposure group (n=12 per group). A whole-body dynamic inhalation exposure system was used to simulate greenhouse exposure. Rats in the control group were exposed to clean air, whereas those in the exposure groups were exposed to β-CYP (55 mg·m⁻³), EMB (7.8 mg·m⁻³), or their combination for 2 h per day for 90 consecutive days. After exposure, ovarian and serum estradiol (E₂) levels were determined in six rats from each group, while the remaining six rats were mated. Of the mated rats, three per group were sacrificed on gestational day 18, and the other remaining three were allowed to deliver naturally. Pregnancy outcomes and fetal development were evaluated. Placental morphology, progesterone (Prog) levels, progesterone synthesis-related factors, oxidative stress, mitochondrial function, and mitophagy-related indicators were subsequently assessed. Results Compared with the control group, fetal body weight on gestational day 18 and neonatal body weight were significantly decreased, whereas the incidence of IUGR was significantly increased in the β-CYP, EMB, and co-exposure groups (P<0.05). The EMB and co-exposure groups exhibited an increased proportion of the placental junctional zone thickness to total placental thickness and a reduced proportion of the labyrinth zone (P<0.05). Ovarian E₂ and placental Prog levels were decreased in all three exposure groups. In addition, the placental expression of cytochrome P450 family 11 subfamily A member1(CYP11A1)、3β-hydroxysteroid dehydrogenase type 1(HSD3B1)、progesterone receptor(PgR) was downregulated, catalase (CAT) activity and adenosine triphosphate (ATP) content were reduced, and lactate dehydrogenase (LDH) activity was increased in all exposure groups (P < 0.05). Furthermore, the expression of translocase of outer mitochondrial membrane 2 was decreased, whereas the expression levels of microtubule-associated protein 1 light chain 3 (LC3), PTEN-induced kinase 1 (PINK1), parkin RBR E3 ubiquitin-protein ligase (Parkin), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) were increased in all exposure groups (P<0.05). Conclusion Prenatal exposure to β-CYP and EMB can cause structural damage to the rat placenta, affect the expression of markers related to progesterone synthesis, and is accompanied by oxidative stress, mitochondrial dysfunction, and alterations in PINK1/Parkin-mediated mitochondrial autophagy, ultimately affecting the intrauterine growth and development of the fetus.

Objective:To investigate the mechanism by which histone deacetylase 6 (HDAC6) exerts immune protective effects in Chlamydia trachomatis respiratory tract infection. Methods:Wild-type (WT) C57BL/6 mice and HDAC6 gene knockout (HDAC6 -/-) mice were used to establish mouse models of Chlamydia muridarum ( Cm) respiratory infection by nasal inhalation of Cm. qPCR and Western blot were used to detect the relative expression of HDAC6 in lung tissues of WT mice after Cm infection. Intracellular factor staining was used to detect the percentages and absolute numbers of CD4 + T cell subsets (Th1, Th17 and Th2 cells)in mouse lung tissues after infection. The levels of IL-4 in spleen cell culture supernatants were measured by ELISA. One-way or two-way analysis of variance (ANOVA) was used for statistical analysis. Results:Cm respiratory tract infection significantly promoted the expression of HDAC6 at both mRNA and protein levels in lung tissues of WT mice ( P<0.001). HDAC6 -/- mice lost more weight than WT mice and took longer to recover to the normal level. Chlamydia load ( P<0.001 and P<0.05) and pathological damage ( P<0.05 and P<0.000 1) in lung tissues were more serious in HDAC6 -/- mice than in WT mice at 7 and 14 d after infection. Neither the percentage nor the absolute number of Th1 (CD4 + IFN-γ + T) and Th17 (CD4 + IL-17 + T) cells showed significant differences between WT and HDAC6 -/- mice, while the percentage and absolute number of Th2 (CD4 + IL-4 + T) cells increased in HDAC6 -/- mice ( P<0.05 and P<0.01). Moreover, in HDAC6 -/- mice, the expression of IL-4 mRNA increased ( P<0.000 1) and the level of IL-4 in the splenic cell culture supernatants increased ( P<0.01). Conclusions:HDAC6 plays an immune protective role in Cm infection. It can reduce the susceptibility of host to Cm respiratory tract infection and alleviates the pathological damage in lung tissues by inhibiting the immune response of Th2 cells.

Objective:To digitally measure the three-dimensional (3D) size of primary tooth crowns and the dimensions of the dental arch in children with individual normal primary dentition, preliminarily obtaining baseline data on the 3D size of primary tooth crowns as well as the length and width of the dental arch, and their influence factors. This study aims to provide a data foundation for the design of reference models for primary dentition.Methods:From May to June 2021, 122 caries-free children aged 3.5-4.5 years with individual normal occlusion were selected from five kindergartens in Haidian District, Beijing. Impressions were taken and plaster models were cast. After preliminary screening, 67 eligible models were scanned to obtain digital dental models. Digital measurement software was used for landmark-based measurements. Parameters included 3D crown dimensions (mesiodistal diameter, buccolingual diameter, and occlusogingival height), dental arch dimensions (length and width at specific regions), and occlusal measurements (overjet and overbite at the primary central incisors, and Bolton index for anterior and full dentition). Gender differences in crown dimensions and bilateral symmetry of homologous teeth, as well as the correlations between arch dimensions and gender, height, weight, and body mass index (BMI) were analyzed.Results:The homonymous teeth of 67 children exhibited strong bilateral symmetry in all 3D dimensions ( P>0.05). Gender differences were observed in the buccolingual dimension for all deciduous molars except for the right mandibular first deciduous molar ( P<0.05). For the occlusogingival dimension, gender differences were found in the right maxillary first and second deciduous molars, left maxillary first deciduous molar, and left mandibular first and second deciduous molars ( P<0.05). For the mesiodistal dimension, only the left mandibular second deciduous molar and right mandibular deciduous canine showed gender differences ( P<0.05). All significant differences above indicated larger dimensions in boys compared to girls. In both maxillary and mandibular arches, the lengths and widths at various locations were significantly larger in boys than in girls ( P<0.05). Univariate correlation analysis revealed that body weight was positively correlated with the width of the terminal plane in both the maxilla and mandible and the total length of the mandibular dental arch, while BMI was positively correlated with the width of the maxillary terminal plane and the widths at all measured sites in the mandible ( P<0.05). Multiple regression analysis demonstrated that, after controlling for relevant variables, BMI was a significant positive predictor for the lengths and widths at various sites of the dental arch ( P<0.05), and height was a positive predictor for dental arch length ( P<0.05), as well as body weight was a positive predictor for the width in the molar region ( P<0.05). Overjet at the primary central incisors was 2.28 (1.57, 2.66) mm, and overbite was 1.13 (0.75, 1.92) mm. The anterior Bolton index was 0.79±0.03, and the overall Bolton index was 0.94±0.03. Conclusions:Primary tooth crowns of individual normal occlusion children demonstrate strong bilateral symmetry in homologous teeth. Most primary molars exhibit gender differences in buccolingual and occlusogingival dimensions, with larger values in boys. Arch dimensions (length and width) are consistently larger in boys.

Objective:To digitally measure the three-dimensional (3D) size of primary tooth crowns and the dimensions of the dental arch in children with individual normal primary dentition, preliminarily obtaining baseline data on the 3D size of primary tooth crowns as well as the length and width of the dental arch, and their influence factors. This study aims to provide a data foundation for the design of reference models for primary dentition.Methods:From May to June 2021, 122 caries-free children aged 3.5-4.5 years with individual normal occlusion were selected from five kindergartens in Haidian District, Beijing. Impressions were taken and plaster models were cast. After preliminary screening, 67 eligible models were scanned to obtain digital dental models. Digital measurement software was used for landmark-based measurements. Parameters included 3D crown dimensions (mesiodistal diameter, buccolingual diameter, and occlusogingival height), dental arch dimensions (length and width at specific regions), and occlusal measurements (overjet and overbite at the primary central incisors, and Bolton index for anterior and full dentition). Gender differences in crown dimensions and bilateral symmetry of homologous teeth, as well as the correlations between arch dimensions and gender, height, weight, and body mass index (BMI) were analyzed.Results:The homonymous teeth of 67 children exhibited strong bilateral symmetry in all 3D dimensions ( P>0.05). Gender differences were observed in the buccolingual dimension for all deciduous molars except for the right mandibular first deciduous molar ( P<0.05). For the occlusogingival dimension, gender differences were found in the right maxillary first and second deciduous molars, left maxillary first deciduous molar, and left mandibular first and second deciduous molars ( P<0.05). For the mesiodistal dimension, only the left mandibular second deciduous molar and right mandibular deciduous canine showed gender differences ( P<0.05). All significant differences above indicated larger dimensions in boys compared to girls. In both maxillary and mandibular arches, the lengths and widths at various locations were significantly larger in boys than in girls ( P<0.05). Univariate correlation analysis revealed that body weight was positively correlated with the width of the terminal plane in both the maxilla and mandible and the total length of the mandibular dental arch, while BMI was positively correlated with the width of the maxillary terminal plane and the widths at all measured sites in the mandible ( P<0.05). Multiple regression analysis demonstrated that, after controlling for relevant variables, BMI was a significant positive predictor for the lengths and widths at various sites of the dental arch ( P<0.05), and height was a positive predictor for dental arch length ( P<0.05), as well as body weight was a positive predictor for the width in the molar region ( P<0.05). Overjet at the primary central incisors was 2.28 (1.57, 2.66) mm, and overbite was 1.13 (0.75, 1.92) mm. The anterior Bolton index was 0.79±0.03, and the overall Bolton index was 0.94±0.03. Conclusions:Primary tooth crowns of individual normal occlusion children demonstrate strong bilateral symmetry in homologous teeth. Most primary molars exhibit gender differences in buccolingual and occlusogingival dimensions, with larger values in boys. Arch dimensions (length and width) are consistently larger in boys.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Objective In this study,we aimed to predict the inhibitory mechanism of Shenlingcao oral liquid(SLC)in non-small cell lung cancer(NSCLC)by network pharmacology and verify it by molecular docking and in vivo experiments.Methods The active ingredients and corresponding targets of SLC and NSCLC were obtained by database and literature search.Targets of SLC common to NSCLC were selected to construct the protein interaction network,and GO and KEGG enrichment analysis and molecular docking were performed.A Lewis lung cancer mouse model was constructed and divided into Model group,SH group,and SL group.The latter two groups were intragastrically administered 8.75 g SLC lyophilized powder/kg and 3.50 g SLC lyophilized powder/kg,respectively.After 14 days of drug intervention,tumor growth,pathological changes in tumor tissue,and apoptosis in tumor tissue were observed in tumor-bearing mice;changes in blood routine indexes and the tumor tissue expression of p-AKT,AKT,p-PI3K,PI3K,and Bcl-2 protein of mice were detected.The result of the KEGG enrichment analysis were verified.Results Network pharmacological analysis showed that there were 77 active ingredients,618 potential targets,1498 potential targets for NSCLC,and 179 drug and disease intersection targets.Target intersection enrichment analysis showed that they were mainly concentrated in the phosphatidylinositol 3 kinase-protein kinase B(PI3K-AKT)signaling pathway,mitogen-activated protein kinase(MAPK)signaling pathway,and other related pathways.Molecular docking showed that the top 10 core components had good bonding ability with the top 10 core targets.In the animal experiments,compared with the Model group,SH group and SL group had significantly decreased tumor volume and weight(P＜0.05,P＜0.01),and significantly decreased white blood cell,neutrophil,and monocyte numbers(P＜0.01,P＜0.001).Red blood cells,platelets,and hemoglobin were significantly increased(P＜0.05,P＜0.01,P＜0.001);apoptotic cells were significantly increased in early tumor tissue(P＜0.05,P＜0.01),and the protein expression levels of p-PI3K/PI3K,p-AKT/AKT,and Bcl-2/GAPDH were significantly decreased(P＜0.05,P＜0.01).The expression levels of PI3K,AKT1,and Bcl-2 genes were significantly decreased(P＜0.05,P＜0.01).Conclusions The mechanisms of SLC activity against NSCLC may be related to the activation of the PI3K-AKT pathway and the promotion of apoptosis.

Objective:To explore the molecular mechanism by which the methionine adenosyltransferase 2A (MAT2A)/β-catenin/zinc finger E-box binding homeobox 1 (ZEB1)/epithelial-mesenchymal transition (EMT) pathway regulates neural tube defect (NTD) through intracellular S-adenosylmethionine (SAM).Methods:A mouse NTD model was induced using the SAM metabolic disorder inhibitor ethionine. Eighty specific pathogen-free C57BL/6 mice were divided into three groups: a normal group (36 mice), an ethionine group (46 mice), and an ethionine+SAM group (44 mice). Phosphate-buffered saline (PBS), ethionine, and ethionine+SAM were respectively injected intraperitoneally on embryonic day 7.5 (E7.5), and the mice were sacrificed on E10.5. Embryonic tissues were collected, and the morphology of embryos in each group was observed under a stereomicroscope. The interaction between ethionine and MAT2A was analyzed using Autodock software. The expression levels of MAT2A, β-catenin, ZEB1, and EMT-related proteins in the brain tissues of embryos from the three groups were measured using immunofluorescence, immunohistochemistry, Western blotting, enzyme-linked immunosorbent assay (ELISA), and real-time quantitative polymerase chain reaction (RT-qPCR). Variance analysis was used for intergroup comparisons.Results:(1) Autodock analysis results showed that MAT2A binds to ethionine through covalent bonds, exhibiting a complementary effect, thereby accelerating the expression of MAT2A. (2) After successful construction of the NTD model, normal embryos were plump with well-developed brains. NTD embryos showed delayed development, obvious anencephaly, unclosed neural tubes, and asymmetry. (3) The levels of SAM and SAH in the embryonic tissues of the ethionine group were significantly lower than those in the normal group (1 737.56±95.64 vs. 872.33±205.11, and 89.17±9.50 vs. 51.25±9.48, respectively). The SAM and SAH levels in the ethionine+SAM group was 1 197.00±222.27 and 66.61±12.25, significantly higher than those in the ethionine group ( P<0.017). Compared with the normal group and the ethionine+SAM group, the expression of MAT2A mRNA in the embryonic brain tissue of the ethionine group was significantly upregulated (1.00±0.00, 1.59±0.52, and 2.42±0.53, respectively, F=49.64, P<0.001; pairwise comparisons between groups P<0.017). (4) Compared with the normal group, the expression of Ctnnb1 in the ethionine group was reduced, and the expression of Ctnnb1 in the ethionine+SAM group was higher than that in the ethionine group (1.00±0.00, 0.38±0.16, and 0.76±0.10, respectively, F=149.03, P<0.001; pairwise comparisons between groups P<0.017). (5) The expression of ZEB1 in the ethionine group was higher than that in the normal group and the ethionine+SAM group (2.91±0.55, 1.00±0.00, and 1.61±0.20, respectively, F=150.01, P<0.001; pairwise comparisons between groups P<0.017). (6) The expression levels of E-cadherin and Vimentin in the ethionine group were lower than those in the normal group. In contrast, the expression of N-cadherin was higher than that in the normal group. After SAM supplementation, the expression levels of E-cadherin and Vimentin were upregulated, and the expression level of N-cadherin was downregulated (0.54±0.12, 1.00±0.00, and 0.72±0.14, respectively, F=87.44; 0.53±0.17, 1.00±0.00, and 0.76±0.09, F=87.44; 3.11±0.53, 1.00±0.00, and 2.13±0.56, F=95.54; all P<0.001; pairwise comparisons within the same index group P<0.017]). Conclusions:Ethionine promotes the expression of MAT2A, leading to reduced SAM production. Ethionine regulates the level of ZEB1 by increasing MAT2A and inhibits the EMT process to interfere with methionine cycle metabolism, ultimately resulting in NTD.

Objectives:This study aims to evaluate the relationship between the triglyceride-glucose body mass index(TyG-BMI),the right pericoronary fat attenuation index(RCA-FAI),and prognosis in patients with coronary artery disease(CAD).Methods:This study included 513 CAD patients who underwent coronary computed tomography angiography(CCTA)and coronary angiography between April 2018 and June 2023.Data collection and parameter calculations were performed for all research variables.The patients were stratified into three groups based on TyG-BMI tertiles:T1 group(TyG-BMI≤207.02,n=171),T2 group(207.02

With the increasing aging of the population in China,the problem of cognitive decline with age is becoming more prominent,and how to move forward to maintain and improve cognitive function in older adults has become an important research topic.Active participation in social activities has a protective effect on cognitive function in older adults.This paper summarizes the concepts of social activities,relationships with cognitive function,and strategies for promoting interventions.The corresponding nursing inspirations were proposed,aiming to provide new perspectives for improving cognitive function in older adults.

Purpose To evaluate the application value of CE-Boost technology in head and neck CT angiography(CTA)with low tube voltage,low contrast agent dosage and low injection rate.Materials and Methods A prospective study was conducted on patients who underwent head and neck CTA at Ji'nan People's Hospital Affiliated to Shandong First Medical University from September to December 2023.Using block randomization,patients were divided into group A(n=30)and group B(n=30).Group A underwent conventional scanning with 120 kV tube voltage,50 ml iodinated contrast agent and 5.0 ml/s injection rate;while group B underwent scanning with 100 kV tube voltage,30 ml iodinated contrast agent and 3.0 ml/s injection rate.CE-Boost images(group B2)were generated by performing flexible subtraction between the enhanced images of group B(group B1)and non-contrast images.CT values,noise,signal-to-noise ratio and contrast-to-noise ratio of major vessels were measured and calculated.Subjective image quality was assessed using a 5-point scale.Vascular CT values,noise,signal-to-noise ratio,contrast-to-noise ratio,subjective scores and radiation dose were compared among the three groups.Results No significant differences in noise were observed among group A,B1 and B2(all P>0.05).The aortic arch CT values,signal-to-noise ratio and contrast-to-noise ratio in group B2 were significantly higher than those in group B1 and A(all P<0.05),while group B1 exhibited significantly lower values than group A(all P<0.05).For other vessels,group B2 demonstrated significantly higher CT values,signal-to-noise ratio and contrast-to-noise ratio than group B1(all P<0.05),but no significant differences were found compared with group A(all P>0.05).Subjective scores were significantly higher in group A[5(5,5)point]and group B2[5(5,5)point]than in group B1[4(3,4)point](Z=-4.790,-4.564,both P<0.001),with no significant difference between groups A and B2(Z=-1.076,P=0.163).Group B reduced iodine intake and injection rate by 40%compared with group A(iodine intake:11.1 g vs.18.5 g;injection rate:3.0 ml/s vs.5.0 ml/s)and achieved a 30%reduction in effective radiation dose[(1.02±0.95)mSv vs.(1.44±1.66)mSv,t=12.217,P<0.001].Conclusion For patients with body mass index<28 kg/m2,CE-Boost combined with 100 kV tube voltage,30 ml iodinated contrast agent and 3.0 ml/s injection rate in head and neck CTA significantly reduces radiation dose,iodine load and injection rate while maintaining image quality.