Objective To explore the application value of dual-phase dual-energy CT (DECT) perfusion imaging in preoperative lung function assessment of lung cancer patients. Methods Data were collected from patients with stageⅠA non-small cell lung cancer who underwent surgical treatment in the Department of Thoracic Surgery, the First Affiliated Hospital of Nanjing Medical University, from November 2022 to June 2024. All patients underwent DECT perfusion imaging and pulmonary function testing (PFT) before surgery. PFT observation indicators included ventilation function indicators such as forced expiratory volume in one second (FEV1), forced vital capacity (FVC), 1-second rate (FEV1/FVC), maximal voluntary ventilation (MVV), and diffusion function indicators such as diffusing capacity for carbon monoxide (DLCO) and DLCO per liter of alveolar volume (DLCO/VA). The software eXamine was used to obtain quantitative parameters of DECT perfusion imaging, including volume parameters and perfusion parameters of both lungs and each lung lobe. The correlation between the volume parameters and perfusion parameters of both lungs and the ventilation and diffusion function indicators of the patients, as well as the differences in quantitative parameters of each lung lobe, was analyzed. Results The end-inspiration lung volume and biphasic volume difference were strongly positively correlated with FEV1 and FVC (r=0.636, r=0.682, r=0.614, r=0.624, P<0.001) and moderately positively correlated with MVV and DLCO (r=0.499, r=0.514, r=0.549, r=0.447, P<0.001); the end-expiration lung volume was weakly negatively correlated with DLCO/VA (r=−0.295, P=0.026); the volume ratio was positively correlated with FEV1, FVC, MVV, and MVV% (r=0.424, r=0.399, r=0.415, r=0.310, P<0.05); the end-inspiration iodine content was weakly positively correlated with DLCO/VA% (rs=0.292, P=0.030); the end-expiration iodine content was weakly positively correlated with FEV1, FVC, MVV, DLCO%, and DLCO/VA (r=0.307, r=0.299, r=0.295, r=0.366, r=0.320, P<0.05) and moderately positively correlated with DLCO (r=0.439, P<0.001); the end-inspiration iodine concentration was negatively correlated with FEV1, FVC, MVV, and MVV% (rs=−0.407, rs=−0.426, rs=−0.352, rs=−0.277, P＜0.05); the end-expiratory phase iodine concentration was moderately positively correlated with DLCO/VA (r=0.403, P=0.002); both the iodine concentration difference and the iodine concentration ratio were moderately positively correlated with FEV1, FEV1%, FVC, MVV, MVV% (P<0.05). The lung volume and iodine concentration ratio values were both highest in the left upper lung lobe and lowest in the right middle lung lobe; the differences in lung volume, lung volume ratio, intrapulmonary iodine content, and intrapulmonary iodine concentration were all highest in the lower lobes of both lungs and lowest in the middle lobe of the right lung. Conclusion Dual-phase DECT perfusion imaging can accurately assess overall lung function and quantify regional lung function.

ObjectiveTo analyze the epidemiological characteristics of clustered vomiting and diarrhea outbreaks in Minhang District of Shanghai, to identify the influencing factors of outbreak scale and duration of epidemic, and to provide scientific evidence for further strengthening surveillance early-warning efforts in key settings and for optimizing prevention and control measures. MethodsThe data for describing epidemiological characteristics of clustered vomitting and diarrhea outbreaks in Minhang District from 2018 to 2023 were collected, multivariable logistic regression models were applied to analyze the influencing factors for epidemic scale,and Spearman rank correlation analyses were applied to analyze the factors duration. ResultsA total of 136 clustered vomiting and diarrhea outbreaks were reported in Minhang District from 2018 to 2023, all occurring in school settings, with an overall attack rate of 0.90%. The outbreaks exhibited distinct seasonality, predominantly occurring from October to December (43.38%) and March to May (32.35%). The primary settings were preschools (45.59%) and elementary schools (44.12%), with students accounted for the majority of cases (99.48%). The predominant clinical manifestation was vomiting (90.44%), with person-to-person contact being the primary transmission route (98.53%). Norovirus genogroup Ⅱ was identified as the main pathogen (71.32%). Standardized terminal disinfection of outbreak sites (OR=0.39, 95%CI=0.20‒0.74) and effective isolation of affected classes (OR=0.23, 95%CI=0.09‒0.57) were significant protective factors for reducing outbreak scale. Both response time (r=0.64, P<0.001) and the number of case generations (r=0.71, P<0.001) showed positive correlations with outbreak duration. ConclusionSchools are the key settings for the prevention and control of clustered vomiting and diarrhea outbreaks in Minhang District, with peak occurring in autumn and spring. Early detection, timely reporting, and prompt response to outbreaks are crucial. Strengthening school-based surveillance systems and standardizing outbreak management protocols are of particular importance.

A redox-responsive hyaluronic acid-vitamin E polyethylene glycol succinate nanoparticle loaded with paclitaxel (HA-SS-TPGS@PTX) was designed to investigate its mechanism for overcoming multidrug resistance (MDR) in non-small cell lung cancer (NSCLC) in vitro. HA-SS-TPGS@PTX nanoparticles were prepared using an emulsion-ultrasonication method. Techniques such as flow cytometry and confocal laser scanning microscopy (CLSM) were employed to study their effects on apoptosis induction, mitochondrial function, and the regulation of P-glycoprotein (P-gp) expression in PTX-resistant lung cancer cells (A549/T). Results showed that HA-SS-TPGS@PTX nanoparticles significantly inhibited the proliferation of A549/T cells in vitro, with an IC50 of 1.35 μg/mL. The nanoparticles entered the cells via CD44 receptor-mediated endocytosis. The high intracellular concentration of glutathione (GSH) triggered the release of PTX and TPGS, which subsequently induced a decrease in mitochondrial membrane potential, leading to apoptosis. Meanwhile, HA-SS-TPGS@PTX also inhibited P-gp expression and ATP consumption, thereby blocking drug efflux. The design of HA-SS-TPGS@PTX provides a new strategy for overcoming MDR in NSCLC.

Objective To investigate the effect and mechanism of Xuanfu Daizhe Decoction on the proliferation,migration,and invasion activities of esophageal cancer cells.Methods Human e-sophageal cancer cell line EC 109 was treated with Xuanfu Daizhe Decoction at different concentrations,and the cells were divided into high-concentration group(200 μg/mL),medium-concentration group(100 μg/mL),low-concentration group(50 μg/mL),and blank group(0 μg/mL)based on the concentration.CCK-8 assay,wound healing assay,and Transwell invasion assay were used to detect the proliferation,migration,and invasion activities of the cells in each group,respectively.Western blot and cellular immunofluorescence staining were employed to detect the protein expression levels of glycolysis-related enzymes[hexokinase 2(HK2),lactate dehydrogenase A(LDHA),and phospho-fructokinase 1(PFK1)]in the cells of each group,and real-time quantitative fluorescent polymerase chain reaction(qRT-PCR)was used to detect the relative expression levels of mRNA encoding these enzymes.A nude mouse tumor-bearing model was established and divided into control group and Xuanfu Daizhe Decoction-fed group(20 mg/kg)to observe the effect of Xuanfu Daizhe Decoction on the growth of esophageal cancer in vivo.Results The results of CCK-8 assay,wound healing as-say,and Transwell invasion assay showed that Xuanfu Daizhe Decoction could inhibit the prolifera-tion,migration,and invasion activities of EC 109 cells in a concentration-dependent manner.West-ern blot and cellular immunofluorescence analysis revealed that compared with the blank group,the protein expression levels of HK2,LDHA,and PFK1 in the low-concentration,medium-concentra-tion,and high-concentration groups were decreased(P＜0.05).The qRT-PCR results showed that compared with the blank group,the relative expression levels of HK2 mRNA,LDHA mRNA,and PFK1 mRNA in the low-concentration,medium-concentration,and high-concentration groups were all reduced(P＜0.01 or P＜0.000 1).The tumor volume in the subcutaneous tissue on the back of nude mice in the Xuanfu Daizhe Decoction-fed group was smaller than that in the control group,and the protein expression level of LDHA in the tumor tissue of the Xuanfu Daizhe Decoction-fed group was lower than that in the control group,while the expression level of the pro-apoptotic protein Bax was higher than that in the control group(P＜0.05).Conclusion Xuanfu Daizhe Decoction can inhibit the glycolysis process of esophageal cancer cells in a concentration-dependent manner,there-by inhibiting cell proliferation,migration,invasion,and tumor growth in vivo.

Given that ovarian stimulation is vital for assisted reproductive technology (ART) and results in elevated serum estrogen levels, exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary. We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells (mESCs). Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation; mice treated with only normal saline served as controls. Hyperstimulation resulted in high serum estrogen levels, enlarged ovaries, an increased number of aberrant oocytes, and decreased embryo formation. The messenger RNA (mRNA)‍-sequencing of oocytes revealed the dysregulated expression of lysine-specific demethylase 6b (Kdm6b), which may be a key factor indicating hyperstimulation-induced aberrant oocytes and embryos. In vitro, Kdm6b expression was downregulated in mESCs treated with high-dose estrogen; treatment with an estrogen receptor antagonist could reverse this downregulated expression level. Furthermore, treatment with high-dose estrogen resulted in the upregulated expression of histone H3 lysine 27 trimethylation (H3K27me3) and phosphorylated H2A histone family member X (γ-H2AX). Notably, knockdown of Kdm6b and high estrogen levels hindered the formation of embryoid bodies, with a concomitant increase in the expression of H3K27me3 and γ-H2AX. Collectively, our findings revealed that hyperstimulation-induced high-dose estrogen could impair the demethylation of H3K27me3 by reducing Kdm6b expression. Accordingly, Kdm6b could be a promising marker for clinically predicting ART outcomes in patients with ovarian hyperstimulation syndrome.
Female ; Mice ; Demethylation/drug effects* ; Embryonic Stem Cells ; Estrogens/administration & dosage* ; Gene Expression/drug effects* ; Histones/metabolism* ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Mice, Inbred C57BL ; Oocytes ; Ovary/drug effects* ; Reproductive Techniques, Assisted ; Animals

Autism Spectrum Disorders (ASDs) are reported as a group of neurodevelopmental disorders. The structural changes of brain regions including the hippocampus were widely reported in autistic patients and mouse models with dysfunction of ASD risk genes, but the underlying mechanisms are not fully understood. Here, we report that deletion of Trio, a high-susceptibility gene of ASDs, causes a postnatal dentate gyrus (DG) hypoplasia with a zigzagged suprapyramidal blade, and the Trio-deficient mice display autism-like behaviors. The impaired morphogenesis of DG is mainly caused by disturbing the postnatal distribution of postmitotic granule cells (GCs), which further results in a migration deficit of neural progenitors. Furthermore, we reveal that Trio plays different roles in various excitatory neural cells by spatial transcriptomic sequencing, especially the role of regulating the migration of postmitotic GCs. In summary, our findings provide evidence of cellular mechanisms that Trio is involved in postnatal DG morphogenesis.
Animals ; Dentate Gyrus/metabolism* ; Mice ; Morphogenesis/physiology* ; Neurons/pathology* ; Cell Movement ; Mice, Inbred C57BL ; Autism Spectrum Disorder/pathology* ; Mice, Knockout ; Neural Stem Cells ; Male ; Neurogenesis ; Autistic Disorder/genetics*

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Objective:To analyze the clinical and genetic characteristics of three Chinese pedigrees affected with Genetic epilepsy with febrile seizures plus (GEFS+ ).Methods:Three GEFS+ probands and their pedigree members presented at the Children′s Hospital of Zhengzhou University from January 2020 to December 2021 were selected as the study subjects. Clinical data of the pedigrees were collected. Whole exome sequencing was carried out for the probands, and Sanger sequencing was used to verify the candidate variants.Results:Proband 1 was a 3-year-and-2-month-old male with febrile seizure plus. His father, two aunts, grandmother, aunt grandmother, uncle grandfather, and paternal great-grandmother also had onset of febrile seizures at 1 ~ 2 years of age with remission before 6 years old. Proband 2 was a 1-year-and-4-month-old male with complex febrile seizure. His mother, maternal uncle, and maternal grandmother also had febrile seizures before 5 ~ 6 years of age. Proband 3 was a 3-year-and-11-month-old male with febrile seizure plus. His father and grandfather also had febrile seizures plus with remission at 7 ~ 8 years of age. Genetic testing revealed that proband 1 had harbored a paternally derived heterozygous SCN1A: c. 1613T>C variant, proband 2 had harbored a maternally derived heterozygous SCN1A: c. 2804A>G variant, and proband 3 had harbored a paternally derived heterozygous SCN1A: c. 1271T>C variant. All of the three variants were predicted as likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (PM1+ PM2_Supporting+ PP1+ PP3+ PP4). Conclusion:The c. 1613T>C, c. 2804A>G and c. 1271T>C variants probably underlay the pathogenesis of GEFS+ in these pedigrees.

Objective:To explore the clinical and genetic characteristics of four children with Kabuki syndrome (KS) due to variants of KMT2D gene. Methods:Four children with KS diagnosed at the Children′s Hospital of Shanxi Province between January 2020 and December 2022 were selected as the study subjects. Whole exome sequencing was carried out for the children and their family members. Candidate variants were verified by Sanger sequencing and pathogenicity analysis.Results:The KS phenotype scores for the four children were 7, 8, 6, and 6, respectively. Child 2 also presented with a rare solitary kidney malformation. Genetic testing revealed that all children had harbored novel de novo variants of the KMT2D gene, including c. 16472_16473del, c. 858dup, c. 11899C>T, and c. 12844C>T, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), all of the variants were classified as pathogenic. Conclusion:For children showing phenotypes such as distinctive facial features, intellectual disability, developmental delay, cardiac abnormalities, and urinary system anomalies, KS should be considered. Early diagnosis and intervention can be achieved through genetic testing, especially in the presence of KMT2D gene mutations.

Objective:To establish an evaluation model for occupational hazard prevention and control levels in coal mines, to explore the combination of Analytic Hierarchy Process (AHP) and fuzzy comprehensive evaluation, to evaluate the overall situation of occupational hazard prevention and control in coal mines.Methods:In November 2021, Collect information of occupational hazards and their prevention and control status in 30 coal mines. AHP model was first constructed for the elements of occupational hazard prevention and control in coal mines. Then, the AHP and fuzzy comprehensive evaluation method was applied to comprehensively evaluate and grade the occupational hazard prevention and control in coal mines, using the principles of maximum membership and weighted average.Results:The hierarchical fuzzy comprehensive evaluation results for typical coal mine were basically consistent with its occupational hazard prevention and control situation. The dust prevention and control situation was good, the noise prevention and control situation is average, the occupational health monitoring situation was good, the occupational health management situation was average, and the overall level of occupational hazard prevention and control was good.Conclusion:The hierarchical fuzzy comprehensive evaluation model for occupational hazard prevention and control levels, combined with the principles of maximum membership and weighted average, can objectively evaluate and reflect the overall situation of occupational hazard prevention and control in coal mines.