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

Objective:To analyze the epidemiological characteristics and spatiotemporal distribution of hepatitis C in Henan province from 2012 to 2022.Methods:The case report data on hepatitis C from counties and districts in Henan between 2012 and 2022 were collected. The distribution characteristics were analyzed by descriptive epidemiological methods, and GeoDa1.2 software was used to perform spatial autocorrelation analysis. The spatiotemporal epidemiological analysis was conducted using SaTScan 10.1 software.Results:A total of 274 485 hepatitis C cases were reported in Henan from 2012 to 2022. The reported annual average incidence rate was 25.84/100 000 and showed an overall downward trend from 2012 to 2022 ( Z=-4.05, P<0.001). More cases were reported in women. The cases were mainly aged 40-69 years and farmers. Spatial autocorrelation analysis showed that the reported cases of hepatitis C present spatial clustering during 2012—2022, and the areas with high incidence were mainly distributed in counties or districts of Zhengzhou, Zhumadian, Xuchang, Zhoukou, and Nanyang. One class I clustering area was detected by spatiotemporal scanning, which mainly covered Xuchang, Pingdingshan and the surrounding counties ( LLR=16 117.73, RR=1.81, P<0.001). Conclusion:The reported cases of hepatitis C in Henan Province show an overall downward trend from 2012 to 2022 and present spatiotemporal clustering. The seasonal regularity of the hepatitis C epidemic is not obvious. People aged 40-69 years old and farmers are the key population for prevention and control.

Objective:To investigate tetanus antibody levels and distribution characteristics in a healthy population of Henan Province.Methods:A cross-sectional survey was conducted in Henan Province from 2022 to 2023 to investigate the permanent population. Enzyme-linked immunosorbent assay (ELISA) was used to detect anti-tetanus toxoid IgG antibody (anti-TT), and the positive rate (≥0.01 IU/ml), protection rate (≥0.1 IU/ml) and concentration differences of tetanus antibodies in different populations were analyzed.Results:The age M ( Q1, Q3) of 5 494 participants was 14 (4, 40) years old, with a minimum age of 8 months and a maximum age of 81 years old. The male-to-female ratio was 1.00∶1.18. The total positive rate, protective rate and mean concentration (MC) [ M ( Q1, Q3)] of Anti-TT were 76.48%, 41.72% and 0.067 (0.010, 0.154) IU/ml, respectively. The positive rates of Anti-TT in individuals aged <3, 3-5, 6-9, and 10-14 were 95.32%, 96.05%, 97.81%, and 93.17%, respectively, but gradually decreased with age ( χ2trend=1 283.02, P<0.001). The antibody protection rate [82.13% (579/705)] and MC [ M ( Q1, Q3) of 0.160 (0.122, 0.259) IU/ml] in the population under 3 years old were relatively high, and both showed a decreasing trend with age (protection rate: χ2trend=1 889.49, P<0.001; MC: t=-54.22, P<0.001). There were significant differences in antibody levels among populations of different ages, regions, occupations, and immunization histories (all P<0.001). Within 13 years after the last dose of TTCV vaccination, the positive rate of Anti-TT was all greater than 90%, but the protection rate and MC continued to decrease with the prolongation of vaccination time (protection rate: χ2trend=160.58, P<0.001; MC: t=-14.93, P<0.001). After the last dose of vaccination, the protection rate and MC [ M ( Q1, Q3)] decreased to 30.43% and 0.055 (0.036, 0.115) IU/ml, respectively, for 10-13 years. The protection rates of Anti-TT for farmers, workers, people aged 60 and above, and women of childbearing age (20-45 years old) were 7.77%, 22.96%, 8.39%, and 12.72%, respectively. Conclusion:The level of tetanus antibodies in infants and young children in Henan Province is relatively high from 2022 to 2023, but it decreases with age and prolonged post-immunization time. There are significant differences in antibody levels among individuals of different ages, regions, occupations, and immunization histories. Occupational high-risk groups such as farmers and workers, elderly people, and women of childbearing age lack sufficient immunization protection.

In February 2025, a local cluster outbreak caused by the D8 genotype Measles virus (MV) was first discovered in Henan Province. Epidemiological investigations and laboratory testing were conducted, including the collection of serum and throat swabs for MV IgM antibody and nucleic acid detection, virus isolation and genetic homology analysis. Measures such as close contact tracing, vaccination rate assessment and supplementary immunization activities were implemented, successfully preventing broader community transmission. A total of three cases were reported during the outbreak, including one imported-related adolescent and two secondary local adult cases. All cases presented with typical symptoms such as fever and rash. Both adult cases were complicated by pneumonia, with one case developing into severe pneumonia. MV genotyping showed that the two secondary cases were both the D8 genotype, with the viral sequences being completely homologous to the Kazakhstan strain. Among the close contacts, 98.2% were adults, and 142 individuals received emergency vaccination.

This research study focuses on addressing the limitations of current neuropathic pain (NP) treatments by developing a novel dual-target modulator, E0199, targeting both Na_V1.7, Na_V1.8, and Na_V1.9 and K_V7 channels, a crucial regulator in controlling NP symptoms. The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP. Through an experimental design involving both in vitro and in vivo methods, E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury (CCI) mouse model. The results demonstrated that E0199 significantly inhibited Na_V1.7, Na_V1.8, and Na_V1.9 channels with a particularly low half maximal inhibitory concentration (IC₅₀) for Na_V1.9 by promoting sodium channel inactivation, and also effectively increased K_V7.2/7.3, K_V7.2, and K_V7.5 channels, excluding K_V7.1 by promoting potassium channel activation. This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses, indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically. The safety of E0199 was supported by neurobehavioral evaluations. Conclusively, E0199 represents a ground-breaking approach in NP treatment, showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP. This study introduces a promising direction for the future development of NP therapeutics.

This study was aimed at exploring the prevalence and drug sensitivity of Gordonia strains isolated from sputum samples in Henan Province,to provide data to aid in the prevention and treatment of Gordonia infection.A combination of 16S rDNA and sec A1 gene sequencing was used to identify the isolated strains,and susceptibility to16 drugs was determined with the broth microdilution method.A total of 21 strains were identified through 16S rDNA gene and sec A1 gene sequencing,including five strains of Gordonia broncians,eight strains of Gordonia paraphernivans,seven strains of Gordonia sputi,and one strain of Gordonia aichiensis.Drug sensi-tivity testing showed high Gordonia sensitivity to drugs such as ceftriaxone,linezolid,doxycycline,amoxicillin/clavulanic acid,mino-cycline,cefotaxime,trimethoprim/sulfamethoxazole,imipenem,tobramycin,and clarithromycin.The sensitivity rates of the isolated strains were 90.48%(19/21),100%(21/21),90.48%(19/21),90.48%(19/21),95.24%(20/21),90.48%(19/21),90.48%(19/21),90.48%(19/21),and 95.24%(20/21),respectively.Gordonia showed high resistance to rifampicin and cefepime,with rates of 28.57%(6/21)and 19.05%(4/21),respectively.Meanwhile,the resistance varied among bacterial strains.The resistance rate of G.sputi to rifampicin reached 71.43%(5/7),whereas that of G.parapffinivoras to cefepime was 37.5%(3/8).The main species of Gordo-nia isolated from sputum samples of patients in Henan Province were G.bronchialis,G.paraffinivoras,G.sputi,and G.aichiensis.Drug sensitivity tests indicated that drugs including amoxicillin/clavulanic acid,ceftriaxone,cefotaxime,tobramycin,clarithromycin,mi-nocycline,trimethoprim/sulfamethoxazole,linezolid,and doxycycline had good antibacterial effects against Gordonia.

This research study focuses on addressing the limitations of current neuropathic pain(NP)treatments by developing a novel dual-target modulator,E0199,targeting both Nav1.7,Nay1.8,and Nay1.9 and Kv7 channels,a crucial regulator in controlling NP symptoms.The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP.Through an experimental design involving both in vitro and in vivo methods,E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury(CCI)mouse model.The results demonstrated that E0199 significantly inhibited Nav1.7,Nav1.8,and Nav1.9 channels with a particularly low half maximal inhibitory concentration(ICs0)for Nay1.9 by promoting sodium channel inactivation,and also effectively increased Kv7.2/73,Kv7.2,and Kv7.5 channels,excluding Kv7.1 by promoting potassium channel acti-vation.This dual action significantly reduced the excitability of dorsal root ganglion neurons and alle-viated pain hypersensitivity in mice at low doses,indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically.The safety of E0199 was supported by neurobehavioral evaluations.Conclusively,E0199 represents a ground-breaking approach in NP treatment,showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe thera-peutic option for NP.This study introduces a promising direction for the future development of NP therapeutics.

Objective To investigate the the levels of magnesium,lead,iron,zinc,copper,manganese,calci-um in whole blood in children aged 0-12 years in Henan province,understand the health status of children and provide a basis for their nutrition and health management.Methods Data were collected from totally 135 385 children aged 0-12 years who underwent trace element testing at Zhengzhou Kingmed Clinical Labo-ratory Inc.from 2019 to 2023 were selected,and agilent inductively coupled plasma mass spectrometer was used to detect seven elements(magnesium,lead,iron,zinc,copper,manganese,and calcium).The elemental detection method in the laboratory has been strictly methodologically verified,and has participated in the ex-ternal quality assessment organized by National Center for Clinical Laboratories.Grouping was conducted based on gender,age,season,region,and year to compare the deficiencies and lead exceedances of six elements(magnesium,iron,zinc,copper,manganese,calcium)under different conditions.Results In this study,the mean P-values of seven elements in different age groups,gender groups,year groups,and regional groups were all＜0.001.Except for lead with a P-value of 0.002,all other elements in different season groups were＜0.001.The P-values were all less than 0.05,indicating statistically significant differences.Among them,Mag-nesium,iron,and zinc in children's whole blood showed an increasing trend with age,while copper,manga-nese,and calcium showed a decreasing trend with age.The proportions of children aged 0-1 years with iron,zinc,and manganese deficiencies were the highest,at 24.70％,48.20％,and 0.65％,respectively.The highest proportion of copper and calcium deficiency was in the age range of 11-12 years old,accounting for 20.43％and 0.17％respectively.The highest proportion of lead exceeding the standard was 0.87％among children aged 0-1.Except for manganese and calcium levels,the levels of the other five elements were higher in boys than in girls.Magnesium and copper levels were highest in spring,iron,zinc,and calcium levels were highest in winter,and manganese and lead levels were highest in summer.Magnesium deficiency,calcium deficiency,and lead excess were showing a decreasing trend year by year.Among them,the lead levels of children in Sanme-nxia and Jiyuan were relatively high compared to other areas.Conclusion 0-2 years children are mainly char-acterized by calcium and zinc deficiency in Henan province.Attention should be paid to iron and zinc supple-mentation in infants and young children.At the same time,it should also be noted that the deficiency rate of copper increases with age,and attention should be paid to the supplementation of copper in children.

Objective:To analyze the epidemiological characteristics and spatiotemporal distribution of hepatitis C in Henan province from 2012 to 2022.Methods:The case report data on hepatitis C from counties and districts in Henan between 2012 and 2022 were collected. The distribution characteristics were analyzed by descriptive epidemiological methods, and GeoDa1.2 software was used to perform spatial autocorrelation analysis. The spatiotemporal epidemiological analysis was conducted using SaTScan 10.1 software.Results:A total of 274 485 hepatitis C cases were reported in Henan from 2012 to 2022. The reported annual average incidence rate was 25.84/100 000 and showed an overall downward trend from 2012 to 2022 ( Z=-4.05, P<0.001). More cases were reported in women. The cases were mainly aged 40-69 years and farmers. Spatial autocorrelation analysis showed that the reported cases of hepatitis C present spatial clustering during 2012—2022, and the areas with high incidence were mainly distributed in counties or districts of Zhengzhou, Zhumadian, Xuchang, Zhoukou, and Nanyang. One class I clustering area was detected by spatiotemporal scanning, which mainly covered Xuchang, Pingdingshan and the surrounding counties ( LLR=16 117.73, RR=1.81, P<0.001). Conclusion:The reported cases of hepatitis C in Henan Province show an overall downward trend from 2012 to 2022 and present spatiotemporal clustering. The seasonal regularity of the hepatitis C epidemic is not obvious. People aged 40-69 years old and farmers are the key population for prevention and control.

Objective:To investigate tetanus antibody levels and distribution characteristics in a healthy population of Henan Province.Methods:A cross-sectional survey was conducted in Henan Province from 2022 to 2023 to investigate the permanent population. Enzyme-linked immunosorbent assay (ELISA) was used to detect anti-tetanus toxoid IgG antibody (anti-TT), and the positive rate (≥0.01 IU/ml), protection rate (≥0.1 IU/ml) and concentration differences of tetanus antibodies in different populations were analyzed.Results:The age M ( Q1, Q3) of 5 494 participants was 14 (4, 40) years old, with a minimum age of 8 months and a maximum age of 81 years old. The male-to-female ratio was 1.00∶1.18. The total positive rate, protective rate and mean concentration (MC) [ M ( Q1, Q3)] of Anti-TT were 76.48%, 41.72% and 0.067 (0.010, 0.154) IU/ml, respectively. The positive rates of Anti-TT in individuals aged <3, 3-5, 6-9, and 10-14 were 95.32%, 96.05%, 97.81%, and 93.17%, respectively, but gradually decreased with age ( χ2trend=1 283.02, P<0.001). The antibody protection rate [82.13% (579/705)] and MC [ M ( Q1, Q3) of 0.160 (0.122, 0.259) IU/ml] in the population under 3 years old were relatively high, and both showed a decreasing trend with age (protection rate: χ2trend=1 889.49, P<0.001; MC: t=-54.22, P<0.001). There were significant differences in antibody levels among populations of different ages, regions, occupations, and immunization histories (all P<0.001). Within 13 years after the last dose of TTCV vaccination, the positive rate of Anti-TT was all greater than 90%, but the protection rate and MC continued to decrease with the prolongation of vaccination time (protection rate: χ2trend=160.58, P<0.001; MC: t=-14.93, P<0.001). After the last dose of vaccination, the protection rate and MC [ M ( Q1, Q3)] decreased to 30.43% and 0.055 (0.036, 0.115) IU/ml, respectively, for 10-13 years. The protection rates of Anti-TT for farmers, workers, people aged 60 and above, and women of childbearing age (20-45 years old) were 7.77%, 22.96%, 8.39%, and 12.72%, respectively. Conclusion:The level of tetanus antibodies in infants and young children in Henan Province is relatively high from 2022 to 2023, but it decreases with age and prolonged post-immunization time. There are significant differences in antibody levels among individuals of different ages, regions, occupations, and immunization histories. Occupational high-risk groups such as farmers and workers, elderly people, and women of childbearing age lack sufficient immunization protection.