BACKGROUND:Studies have demonstrated that postmenopausal osteoporosis is related to female reproductive characteristics and exercise diets,but few studies have demonstrated whether female reproductive characteristics and exercise diets have an effect on vitamin D in postmenopausal women. OBJECTIVE:To investigate the relationship of vitamin D levels with female reproductive characteristics and exercise diets and their influencing factors in postmenopausal women in Beijing. METHODS:Totally 727 postmenopausal women with an age range of 46-75 years old who received on-site questionnaires in 17 communities of Beijing from September 2017 to May 2018 were selected as the study subjects,and the questionnaires included the subjects'basic information and history of menstruation,menopause,pregnancy,and exercise diet.An electrochemiluminescence immunoassay analyzer and its auxiliary reagents were used to determine 25-(OH)D levels.Bone mineral density and T values of the lumbar spine(L1-L4,whole)and both hips(femoral neck,whole)were determined using a dual-energy X-ray bone mineral density detector.The correlation of vitamin D with reproductive characteristics and exercise diet was observed,as well as the influencing factors of vitamin D were analyzed. RESULTS AND CONCLUSION:There were 136 cases(18.7%)in the vitamin D normal group,389 cases(53.5%)in the vitamin D insufficient group,and 202 cases(27.8%)in the vitamin D deficient group.The mean vitamin D level was(15.60±5.85)ng/mL.With the increase of vitamin D level,the bone mineral density value and T value of different parts of the body also increased.Vitamin D level was positively correlated with age at menarche,days of menstrual duration,stage of menopause,activity,diet type,and dietary preference(P<0.05);was negatively correlated with menstrual cycle,age at menopause,and number of childbearing(P<0.05);and had no correlation with age at first conception and number of pregnancies(P>0.05).The results of multifactorial ordered Logistic regression analyses showed that there was a positive correlation between the frequency of drinking dairy products and vitamin D level(P<0.05),and dairy products were a protective factor for vitamin D level.To conclude,vitamin D levels are generally insufficient and bone mineral density values are generally low in postmenopausal women in Beijing.Vitamin D levels are correlated with some reproductive characteristics and exercise diets,and drinking dairy products is a protective factor.Therefore,it is possible to intervene in the dietary situation of postmenopausal women by means of health education about osteoporosis and by increasing vitamin D levels in order to increase bone density values and reduce the prevalence of osteoporosis in the postmenopausal period.

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

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.

Flagella are important protein structures on the cell surface of bacteria and the main appendage for bacterial swimming. Flagella play a crucial role in bacterial motility, chemotaxis, pathogenicity, and environmental sensing. With the development of microscopic tracking technology and flagellum visualization tools, new forms of flagellar motility and increasing roles of flagella in the physiological activities of bacteria have been discovered. This review introduces the visualization methods of flagella and the applications of these methods in studying flagellar functions, giving insights into exploring the functions of flagella and laying a theoretical foundation for its future applications in inhibiting bacterial transmission and treating bacterial infections.
Flagella/physiology* ; Bacterial Physiological Phenomena ; Chemotaxis/physiology* ; Bacteria

Objective:To understand the regional prevalence and hotspot mutations through analysis of genetic screening results for newborns with pseudohypertrophic muscular dystrophy.Methods:A total of 22 813 newborns (12 065 males and 10 748 females) born at the Women's Hospital of Nanjing Medical University from March 18, 2022, to October 31, 2023, were selected. The Dystrophin gene ( DMD) was detected using chip capture next-generation sequencing technology, followed by bioinformatics analysis. Pathogenic mutations identified were validated using multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing. Serum creatine kinase levels were also tested in suspected male patients. Descriptive analysis was applied for this study. Results:Among the 10 748 girls, 14 carriers of DMD gene were detected (0.013%), of which, nine cases were validated in the family; one case was a de novo mutation, five were inherited from the mother, and three were inherited from the father. The screening identified nine suspected patients among the boys (0.075%), and eight of them were confirmed by family validation, in which three were de novo mutations, and five were inherited from the mother. Among all identified DMD mutations, deletions were the most common one, accounting for 52.2% (12/23), incluling four cases of deletion at 49-51 exon. Conclusions:Newborn genetic screening based on chip capture next-generation sequencing technology combined with bioinformatics analysis is helpful in early detection of patients and carriers of pseudohypertrophy muscular dystrophy. According to the preliminary statistics, the incidence rate of DMD/BMD in this area is 1/1 341 male infants and the hotspot mutation is exon 49 to 51 deletion.

Objective To investigate the correlation between muscle strength level and bone mineral density and bone metabolism indexes in postmenopausal women in Beijing.Methods Postmenopausal women who were investi-gated by on-site questionnaires and followed by bone mineral density examination in Beijing from September 2017 to May 2018 were recruited as study subjects.They were divided into early menopausal group,middle menopausal group,late menopausal group,and twilight menopausal group according to the years of menopause.Changes in grip strength,5 times sit-to-stand test(FTSST)with bone mineral density(BMD)and bone metabolism indexes were observed in the four groups and their correlations were analyzed.Results A total of 815 cases of postmenopausal women were included.At different menopausal stages,muscle strength was all found to decrease with the increase of menopausal years(P＜0.05),there was non-significance of different bone metabolism indexes among the four groups(P＞0.05);Femoral neck and lumbar spine BMD decreased with the increase of menopausal years(P＜0.05).Maximum grip strength was positively correlated with both femoral neck and lumbar spine BMD(R=0.158,P＜0.05;R=0.130,P＜0.05).There was no correlation between muscle strength and bone metabo-lism indexes(P＜0.05).Conclusions Different bone metabolism indexes are not associated with muscle strength in menopausal women.Maximum grip strength is positively correlated with bone mineral density,which can be used as an auxiliary screening tool for osteoporosis(OP)in women.The FTSST suggests that the lower limb muscle strength of menopausal women decreases with age,which can be used as one of the indicators for predicting the risk of falls in menopausal women.

Objective To observe the drainage pathways of interstitial fluid(ISF)and substance clearance pattern in rat brain with fluorescence tracing imaging and treacer-based MRI.Methods Thirty-three male SD rats were randomly divided into fluorescence tracing group(F group,n=18)and treacer-based MRI group(MRI group,n=15),then further divided into thalamic,hippocampal and caudate nucleus subgroups,respectively.Evans blue was injected to rats in F group,and cardiac perfusion was performed after injection,then brain tissue was harvested,and frozen sections were made to observe the drainage pathways of IFS in different subgroups.MRI was performed on rats in MRI group before and after injection of gadolinium-diethylenetriamine pentaacetic acid(Gd-DTPA)to observe signal intensity in ROI of brain regions in different subgroups,the signal unit ratio was calculated,and the changing trend was explored.Results ISF in thalamus,hippocampus and caudate nucleus had different dominant drainage pathways,and the time of tracer reached to adjacent brain regions and whole brain in F group were different.In MRI group,within 4 h after injection of Gd-DTPA,there were differences in direction and clearance rate among tracer in thalamus,hippocampus and caudate nucleus,mainly manifesting as the tracer in thalamus and hippocampus drained to the ipsilateral cortex and lateral ventricle,while the tracer in the caudate nucleus diffused to the cortex and midbrain,and there were differences of the peak time of tracer signal among adjacent drainage brain regions.Conclusion Fluorescence and MR dual-mode imaging showed that there were differences in the dominant drainage pathways of IFS and clearance rates of small molecule substances among hypothalamus,hippocampus and caudate nucleus of rats.

Objective To investigate effects of ligustilide(LIG)on proliferation,apoptosis,angiogenic mimicry and Ras homolog gene family member A(RhoA)/Rho associated coiled coil containing protein kinase 1(ROCK)signaling pathway in esophageal cancer cells.Methods Esophageal cancer cell line EC-109 was treated with LIG at concentrations of 0,12.5,25,50,100,and 200 μmol/L to detect cell activity,and the suitable concentration was selected for subsequent experiments.EC-109 cells were grouped into the control group,the LIG low,medium and high concentration groups(LIG-L,LIG-M and LIG-H groups),and the LIG-H+RhoA activator Naciclassine group(LIG-H+Naciclassine group).Edu was applied to detect cell proliferation,and flow cytometry was applied to detect cell apoptosis.Angiogenetic mimicry was observed.Western blot assay was applied to detect expression levels of proteins related to cell proliferation and apoptosis,and RhoA,ROCK proteins.Nude mouse tumor transplantation experiment was applied to verify the effect of LIG on the growth of esophageal cancer tumors.Immunohistochemistry was applied to detect expression levels of angiogenesis related factors(VEGF),RhoA and ROCK proteins in transplanted tumors.Results Compared with the control group,the vascular mimicry tubular structure of EC-109 cells decreased sequentially in the LIG-L group,the LIG-M group and the LIG-H group.The positive rate of Edu,the expression levels of Cyclin D1,Ki67,Bcl-2,RhoA and ROCK reduced in turn.P21,cell apoptosis rate,the expression of Bax and Caspase-3 increased in sequence(P＜0.05).Naciclasine,RhoA activator,partially reversed the effect of LIG on cell proliferation,apoptosis and vasculogenic mimicry of esophageal cancer cells.Nude mouse transplantation tumor experiment showed that compared with the control group,the growth rate of transplanted tumor showed down,tumor volume decreased and the expression levels of RhoA,ROCK and VEGF decreased in the LIG group(P＜0.05).Conclusion Ligustilide inhibits the proliferation and angiogenic mimicry of esophageal cancer cells by inhibiting RhoA/ROCK signaling pathway,and promotes the apoptosis of esophageal cancer cells.

Objective:To investigate diagnostic and prognostic value of actin-binding protein ANLN in clear cell renal cell carcinoma(ccRCC)and its relationship with tumor microenvironment.Methods:Gene expression data and clinical data for ccRCC were downloaded from The Cancer Genome Atlas(TCGA).Relationship between ANLN expression and clinicopathological features was assessed by Wilcoxon rank sum test and Logistic regression.Receiver operating characteristic(ROC)curve was used to assess diagnostic value of ANLN expression in ccRCC.Kaplan-Meier and Cox regression analysis were used to investigate effect of ANLN expression on overall survival.Gene set enrichment analysis(GSEA)was used to identify signaling pathways associated with ANLN in ccRCC.Relationship between ANLN expression and immune infiltration was analyzed by ESTIMATE algorithm,tumor immune estima-tion resource(TIMER)and CIBERSORT algorithms.Relationship between ANLN and drug sensitivity was calculated using CellMiner database.Results:ANLN expression was significantly upregulated in ccRCC tissues.ANLN expression in ccRCC was correlated with clinicopathological features.ROC analysis showed that ANLN had a high diagnostic value in ccRCC.High ANLN expression was signifi-cantly associated with poor prognosis.Multivariate Cox regression analysis showed that high ANLN expression was an independent risk factor for overall survival in ccRCC patients.GSEA showed that ANLN was associated with multiple signaling pathways.In terms of immunity,ANLN was closely associated with tumor microenvironment,immune infiltration and immune checkpoint molecules in ccRCC.ANLN expression was negatively correlated with sensitivity of most antitumor drugs.Conclusion:ANLN is a potential diagnos-tic and prognostic biomarker and immunotherapeutic target for ccRCC.

Objective:To investigated the relationship between magnetic resonance imaging(MRI)parameters and the molecular pathology of primary central nervous system lymphoma(PCNSL).Methods:We retrospectively analyzed 26 patients from The First Affiliated Hospital of Harbin Medical University between January 2020 and June 2023 classified into germinal center B-cell like(GCB)and non-germinal center B-cell like(non-GCB)groups based on cell origin,into Ki-67≥75%and<75%groups based on the Ki-67 index,into BCL-2+and BCL-2-groups based on BCL-2 expression,and into responsive and non-responsive groups based on their response to MAP+Bruton's tyrosine kinase inhib-itor(BTKi)treatment.We extracted and compared first-order parameters between the groups,including mean value,standard deviation,variance,coefficient of variation,skewness,kurtosis,and entropy from baseline MRI images.Results:Four parameters(variance,kurtosis,skewness,and coefficient of variation)showed no significant differences between groups.However,three parameters(mean,standard devi-ation,and entropy)significantly differed between the groups based on Ki-67 and BCL-2 expression.For the Ki-67 index,the three parameters'areas under the curve(AUC)were 0.731,0.831,and 0.913,respectively.For BCL-2 expression,the mean and standard deviation AUCs were 0.889 and 0.938,respectively.In addition,the mean and entropy parameters significantly differed between the groups categorized by cell origin and treatment responsiveness(P<0.05).Multi-parameter joint analysis demonstrated greater identification accuracy compared to util-izing individual quantitative parameters from texture analysis.Conclusions:The mean,standard deviation,and entropy MRI parameters can help predict Ki-67 and BCL-2 expression in patients with PCNSL and have evaluative functions for treatment.They are beneficial for preoper-ative non-invasive assessment of tumor malignancy,providing vidence for prognosis and treatment planning.