Objective:To investigate the characteristics of the endometrial microbiota in patients with varying degrees of intrauterine adhesion (IUA).Methods:This single-center cross-sectional observational study enrolled 115 patients with IUA who were treated at the Hysteroscopic Center of Fuxing Hospital, Capital Medical University, from May 2022 to October 2023. After quality control and data preprocessing, 81 samples met the inclusion criteria for analysis. Patients were grouped according to an established IUA scoring and grading system into mild IUA ( n=38) and moderate-to-severe IUA ( n=43). Endometrial tissue was collected under sterile conditions. Bacterial genomic DNA was extracted, the 16S rRNA V3-V4 region was amplified, and sequencing was performed on an Illumina platform. Differences in endometrial microbiota diversity and composition were compared between the two groups. Results:Patients with varying degrees of IUA exhibited comparable species richness, evenness and diversity of endometrial microbiota. At the phylum level, the endometrial microbiota across all subjects was predominantly composed of Proteobacteria, Firmicutes, Cyanobacteriota, Bacteroidota, and Actinobacteriota, with Proteobacteria (32.29%) and Firmicutes (23.82%) showing the highest mean relative abundances. At the genus level, Ralstonia (16.67%), Lactobacillus (13.45%), and Streptococcus (7.07%) were the most abundant genera. Group comparisons showed that the abundance of Ralstonia was higher in the mild IUA group, whereas Lactobacillus, Vibrio and Pseudoalteromonas were more abundant in the moderate-to-severe IUA group; however, these differences did not reach statistical significance (all P>0.05). LEfSe analysis further indicated that Lactobacillus, Vibrio, Pseudoalteromonas, Aeromonas, Ureaplasma and Acetobacterium were relatively enriched in the moderate-to-severe IUA group, while Geobacillus, Stomatobaculum and Fusicatenibacter were more abundant in the mild IUA group. Conclusion:The composition of the endometrial microbiota differs among patients with varying IUA severity. IUA progression may be associated with alterations in the endometrial microbiota; however, causal relationships and underlying mechanisms require further investigation.

Endometriosis presents a common challenge in global women's health.Ferroptosis,as an emerging form of regulated cell death,has recently attracted attention in relation to endometriosis.In terms of disease mechanisms,ferroptosis drives ovarian endometrial fibrosis via the induction of iron overload,and promotes disease progression by regulating multiple signaling pathways,such as p38 mitogen-activated protein kinase/signal transducer and activator of transcription 6(p38MAPK/STAT6),promote angiogenesis,autophagy,etc,fueling disease progression.In terms of infertility,ferroptosis affects embryo development and ovarian function,thereby reducing fertility.From a diagnostic perspective,high expression of ferroptosis-related genes provides potential biomarkers for the early diagnosis of endometriosis,effectively distinguishing patients from healthy individuals,and showing important clinical value.In terms of treatment strategies,non-natural compounds such as Erastin,as well as natural compounds such as resveratrol,ursolic acid,and baicalein,have shown potential therapeutic effects in relieving the pathological process and related symptoms of endometriosis.This review comprehensively elucidates the key role of ferroptosis in endometriosis in terms of the disease mechanisms,infertility,diagnosis,and treatment,and explores its potential as a diagnostic biomarker and therapeutic target,thus providing new theoretical support and treatment strategies for the management of endometriosis.

Objective To observe changes of white matter function in adolescent smoker(AS)with resting-state functional MRI(rs-fMRI)fractional amplitude of low-frequency fluctuation(fALFF)technique.Methods Forty-five adolescents(AS group)and 45 control subjects(control group)were prospectively enrolled,and brain rs-fMRI were acquired.Brain regions with fALFF being different between groups were observed,and the correlations with clinical indicators were analyzed.Results Compared with that in control group,fALFF of the right superior longitudinal fasciculus significantly elevated in AS group(FDR correct Q＜0.05),in which the peak of the cluster was positively correlated with score of Fagerstr?m test for nicotine dependence(FTND)(r=0.294,P=0.049).Conclusion White matter function changed in AS,presenting as significantly increased fALFF in right superior longitudinal fasciculus,which was positively correlated with nicotine dependence.

Aim To investigate the regulatory mecha-nisms of donepezil on the expression and enzymatic ac-tivity of cytochrome P450 3A4(CYP3A4),elucidate the synergistic impact of hypoxia on CYP3A4 function,and reveal its potential association with drug-induced cardiotoxicity,particularly QT interval prolongation.Methods Western blot,co-immunoprecipitation,and gene knockdown techniques were employed to evaluate the effects of donepezil and hypoxia on CYP3A4 pro-tein expression.CYP3A4 enzymatic activity was as-sessed using an in vitro incubation system with rat liver microsomes combined with high-performance liquid chromatography(HPLC),and the half-maximal inhib-itory concentration(IC50)was determined.Results Donepezil(10 μmol·L-1)and hypoxia reduced CYP3A4 protein expression to 31.75％and 45.90％of the control levels,respectively.Both interventions activated the gp78-mediated ubiquitin-proteasome path-way,significantly increasing CYP3A4 ubiquitination levels by 2.1-fold compared to the control group,thereby promoting proteasomal degradation.Donepezil inhibited CYP3A4 enzyme activity with an IC50 of 83.4μmol·L-1,and hypoxia synergistically enhanced this inhibitory effect,reducing the IC50 to 20.79 μmol·L-1.Conclusion Donepezil downregulates CYP3A4 function through dual mechanisms involving ubiquitin-mediated proteasomal degradation and direct enzymatic inhibition.Hypoxia potentiates this effect,leading to impaired metabolism of CYP3A4 substrate drugs,ele-vated plasma drug concentrations(1.6-2.3-fold in-crease compared to normal metabolic conditions),and an increased risk of QT interval prolongation and other forms of cardiotoxicity.

Objective To investigate the dynamic functional connectivity differences between insomnia patients and healthy controls in triple brain networks[the significant network(SN),the default mode network(DMN),and the executive control network(ECN)]using functional magnetic resonance imaging,and uncover their associations with cognitive ability.Methods Dynamic functional connectivity analysis was performed on functional magnetic resonance imaging data from 40 insomnia patients and 40 healthy controls.The changes in dynamic functional connectivity values were studied for SN,DMN,ECN[including the left executive control network(LECN)and the right executive control network(RECN)];the similarities and differences in time characteristic indicators such as time score,average dwell time,and conversion rate were explored;and their associations with clinical information were analyzed.Results The SN-LECN and DMN-RECN dynamic functional connectivity was significantly higher in insomnia patients than in healthy controls(P=0.013,0.047),while the RECN-LECN and RECN internal functional connectivity strength was lower in insomnia patients than in healthy controls(P<0.001).Additionally,the fractional time in state 2 in insomnia group was significantly higher than that in healthy controls(P<0.001),and it was positively correlated with the Pittsburgh sleep quality index(r=0.524,P=0.001).Conclusion Insomnia patients exhibit significant abnormalities in triple brain network dynamic functional connectivity,which may be related to abnormalities in cognitive control and sensory processing in insomnia patients.These findings provide a new perspective for further research on the neural mechanisms and potential intervention strategies for insomnia.

Aim To investigate the effects of the fangchinoline derivative LYY-32 on the biological prop-erties of the BLM642-1290 DNA helicase,in order to lay a foundation for further research on its antitumor activity.Methods Fluorescence polarization assay,malachite green-phosphate and ammonium molybdate colorime-try,and fluorescein-labeled DNA gel electrophoresis experiments were conducted to study the effects of fangchinoline derivative LYY-32 on the DNA binding activity,ATPase activity,and DNA unwinding activity of BLM642-1290 DNA helicase.The effects of LYY-32 on the DNA unwinding activity of DNA helicase in cells were studied using fluorescent techniques and time-lapse microscopy.Ultraviolet spectral scanning was used to investigate the effects of LYY-32 on the confor-mation of the BLM642-1290 DNA helicase.Results At a concentration of 10 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to dsDNA was 53.17％.At a concentration of 5 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to ssDNA was 88.49％.The inhibition rate of LYY-32 on the ATPase activity of BLM642-1290 DNA he-licase was 89.3％at a concentration of 50 μmol·L-1.When the concentration of LYY-32 exceeded 5μmol·L-1,its inhibition rate on the DNA unwinding activity of BLM642-1290 DNA helicase was 100％.LYY-32 also significantly inhibited the DNA unwinding ac-tivity of DNA helicase in cells.However,LYY-32 had no effect on the conformation of BLM642-1290 DNA heli-case.Conclusion The DNA binding activity,AT-Pase activity,and DNA unwinding activity of BLM642-1290 DNA helicase could be significantly inhibi-ted by the fangchinoline derivative LYY-32.

Objective:To construct a framework for evaluating the quality of health economic evaluation methodology based on the pragmatic clinical trial.Methods:An evaluation framework was constructed based on existing quality evaluation tools for health economic evaluation other quality evaluation tools.The weights of each item in the framework were determined by the Delphi method,and the weighted average was calculated using the expert authority coefficient.Results:A total of 23 experts were consulted,and the expert authority coefficients were 0.88 and 0.90,respectively.The results of the Wilcoxon signed-rank test showed no statistically signifi-cant differences among the expert opinions in two rounds(P＞0.05).Finally,a framework with 3 dimensions and 8 items was estab-lished.Conclusion:The evaluation framework has high scientificity and reliability.

The health and well-being of the elderly have become a focal point for all sectors of society. As an effective means of preventing and controlling infectious diseases, vaccination plays a critical role in safeguarding human health. For older adults, timely and scientifically guided vaccination can significantly reduce the risk of serious illnesses while alleviating the associated economic burdens and pressure imposed on society. However, in practice, deficiencies in policy support, accessibility of vaccination services, and public awareness hinder some elderly individuals from fully benefiting from the protective effects of vaccines. This paper analyzes current vaccination practices for the elderly globally and proposes strategies to improve vaccination coverage, providing a scientific basis for advancing effective vaccination initiatives for this demographic in China.

Vaccination has become one of the key public health interventions for reducing child mortality. With the implementation of the expanded programme on immunization, the number of vaccine types children need to receive is increasing, necessitating further optimization of childhood immunization strategies. The World Health Organization recommends simultaneous vaccination as one of the core strategies for optimizing childhood immunization schedules. This article analyzes the current status, challenges, and prospects of simultaneous vaccination strategies for children in China, aiming to provide a scientific basis for promoting and implementing strategies for the simultaneous administration of multiple vaccines to children.

Objective:To investigate the characteristics of the endometrial microbiota in patients with varying degrees of intrauterine adhesion (IUA).Methods:This single-center cross-sectional observational study enrolled 115 patients with IUA who were treated at the Hysteroscopic Center of Fuxing Hospital, Capital Medical University, from May 2022 to October 2023. After quality control and data preprocessing, 81 samples met the inclusion criteria for analysis. Patients were grouped according to an established IUA scoring and grading system into mild IUA ( n=38) and moderate-to-severe IUA ( n=43). Endometrial tissue was collected under sterile conditions. Bacterial genomic DNA was extracted, the 16S rRNA V3-V4 region was amplified, and sequencing was performed on an Illumina platform. Differences in endometrial microbiota diversity and composition were compared between the two groups. Results:Patients with varying degrees of IUA exhibited comparable species richness, evenness and diversity of endometrial microbiota. At the phylum level, the endometrial microbiota across all subjects was predominantly composed of Proteobacteria, Firmicutes, Cyanobacteriota, Bacteroidota, and Actinobacteriota, with Proteobacteria (32.29%) and Firmicutes (23.82%) showing the highest mean relative abundances. At the genus level, Ralstonia (16.67%), Lactobacillus (13.45%), and Streptococcus (7.07%) were the most abundant genera. Group comparisons showed that the abundance of Ralstonia was higher in the mild IUA group, whereas Lactobacillus, Vibrio and Pseudoalteromonas were more abundant in the moderate-to-severe IUA group; however, these differences did not reach statistical significance (all P>0.05). LEfSe analysis further indicated that Lactobacillus, Vibrio, Pseudoalteromonas, Aeromonas, Ureaplasma and Acetobacterium were relatively enriched in the moderate-to-severe IUA group, while Geobacillus, Stomatobaculum and Fusicatenibacter were more abundant in the mild IUA group. Conclusion:The composition of the endometrial microbiota differs among patients with varying IUA severity. IUA progression may be associated with alterations in the endometrial microbiota; however, causal relationships and underlying mechanisms require further investigation.