Ulcerative colitis （UC）， which is characterized by a complex and multifactorial etiology， remains one of the challenging disorders in the international field of digestive system diseases. In recent years， rectal administration preparations have made rapid progress in UC therapeutic applications. This study systematically reviews the dosage forms， mechanisms of action， and clinical applications of rectally-administered preparations for the treatment of UC. It is found that suppositories are the most commonly used dosage forms for rectal administration. The newer suppositories have the advantages of high bioavailability and good stability. Enemas can retain the drug in the intestine as much as possible to achieve the effects of diluting intestinal toxins， cleansing the bowel， and reducing inflammation. Gels can achieve a drug-sustained-release effect and effectively improve intestinal mucosal damage. The mechanism of action of this type of preparation is mainly to inhibit inflammatory cell infiltration， regulate intestinal microbial homeostasis， and increase the expression of tight-junction proteins， so as to play anti-inflammatory， regulate the intestinal bacterial flora， repair the intestinal mucosa， and other efficacies. The diversity of rectal administration forms provides a wide range of choices for the clinical treatment of UC， such as Mesalazine suppositories， Lianshao enemas， and temperature- sensitive gels loaded with drugs for UC.

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Objective To comprehensively understand the map of transcripts during mitosis and their regulatory mechanisms of HAP 1 cells by conducting transcriptome sequencing analysis after being released by mitotic synchro-nization arrest.Methods HAP1 cells were subjected to mitotic synchronous arrest with nocodazole and samples were collected after 0,20,80 min release,and RNA sequencing(RNA-seq)were performed.The transcriptome data was cleaned and the differentially expressed genes,expression trend clustering and functional enrichment com-bined with the protein interaction network were analyzed to explore the changes of signaling pathways in HAP 1 cells during mitosis.Results The transcriptome of HAP1 cells after synchronous release from mitosis underwent significant changes in time series,and differential gene cluster analysis revealed four gene clusters were enriched in important biological processes such as p53 signaling and cytoplasmic translation.Conclusions The transcriptome time-dependent dynamic changes during mitosis in HAP1 cells are coordinated regulation of key signaling pathways including cellular stress response,translational control and chromatin remodeling,ensuring a balance between growth and stress response upon mitotic exit.

Objective To explore the therapeutic effects of temperature-controlled radiofrequency combined with electrical stimulation biofeedback on postpartum dyspareunia in women.Methods In this study,166 patients suffering from dyspareunia due to pelvic floor muscle hypertonicity who visited the Pelvic Floor Rehabilitation Medicine Center of our hospital were selected as subjects.They were randomly divided into three groups:the electrical stimulation biofeedback treatment group(55 cases),the radiofrequency treatment group(55 cases),and the combined electrical stimulation biofeedback and radiofrequency treatment group(56 cases).Patients in the electrical stimulation biofeedback therapy group received only electrical stimulation biofeedback therapy;patients in the radiofrequency group were treated solely with radiofrequency therapy;and patients in the combined treatment group began receiving gynecological radiofrequency treatment from the second week,in addition to the same treatment as the electrical stimulation biofeedback treatment group.To evaluate the effectiveness of the three treatment methods,comparative analyses were conducted on the pelvic floor modified Oxford muscle strength measurement results,pelvic floor surface electromyography values,and sexual function(FSFI)scores of the three groups of patients before and after treatment.Results After treatment,the average resting electromyography(EMG)value of the combined treatment group decreased(P＜0.05),indicating a significant improvement in muscle relaxation function.After treatment,the combined treatment group showed significant improvements in the pelvic floor modified Oxford muscle strength test,the maximum EMG value of fast-twitch(type Ⅱ fibers)muscles,the average EMG value of slow-twitch(type Ⅰ fibers)muscles,and the average EMG value of endurance test,and also demon-strated significant improvements in sexual function(FSFI)scores,which were superior to the electrical stimulation biofeedback treatment group and the radiofrequency treatment group(P＜0.05).Conclusion The combined treatment of temperature control radiofrequency and electrical stimulation with biofeedback has shown significant therapeutic effects in the treatment of postpartum dyspareunia,offering a broad prospect for clinical application.

Objective To investigate the clinical efficacy of intravaginal CO2 fractional laser combined with interferon in treating persistent high-risk HPV infection of the cervix and its impact on vaginal microecology.Methods A total of 211 patients with persistent high-risk HPV infection of the cervix who visited Kunming Maternal and Child Health Care Hospital from June 2022 to July 2024 were selected and randomly divided into a follow-up(blank control)group(n=70),an interferon treatment group(n=70),and a combined treatment group(n=71).The follow-up group received regular follow-ups.The interferon treatment group was treated with recombinant human interferon α-2b,and the combined treatment group received a combination of CO2 matrix laser and interferon treatment.The total effective rate,levels of inflammatory factors,and vaginal microecological recovery were compared among the three groups at 3 and 6 months after treatment.Results Overall efficacy:The overall efficacy rates of the combined treatment group at 3 months and 6 months were 73.24%and 81.69%,respectively,significantly higher than those of the interferon group(47.14%and 60.00%)and the blank control group(11.43%and 18.57%)(all P<0.001).Inflammatory factors:Post-treatment levels of IL-1 and TNF-α in the combined treatment group were significantly lower than those in the other two groups(P<0.001).Vaginal microbiota:The combined treatment group had a significantly higher rate of normal PH(84.51%)and normal lactobacillus levels(92.96%)compared to the other two groups(P<0.001).Conclusion CO2 lattice laser combined with interferon can effectively eliminate HPV,improve inflammation and vaginal microenvironment,and demonstrates superior efficacy to monotherapy,with good safety.

Objective Chlorination is often used to disinfect recreational water in large amusement parks;however,the health hazards of chlorination disinfection by-products(DBPs)to occupational populations are unknown.This study aimed to assess the exposure status of chlorinated DBPs in recreational water and the health risks to employees of large amusement parks. Methods Exposure parameters of employees of three large amusement parks in Shanghai were investigated using a questionnaire.Seven typical chlorinated DBPs in recreational water and spray samples were quantified by gas chromatography,and the health risks to amusement park employees exposed to chlorinated DBPs were evaluated according to the WHO's risk assessment framework. Results Trichloroacetic acid,dibromochloromethane,bromodichloromethane,and dichloroacetic acid were detected predominantly in recreational water.The carcinogenic and non-carcinogenic risks of the five DBPs did not exceed the risk thresholds.In addition,the carcinogenic and non-carcinogenic risks of mixed exposure to DBPs were within the acceptable risk limits. Conclusion Typical DBPs were widely detected in recreational water collected from three large amusement parks in Shanghai;however,the health risks of DBPs and their mixtures were within acceptable limits.

Objective To comprehensively understand the dynamic transcriptional landscape during infection through investigating the temporal molecular changes in macrophages RAW 264.7 upon infection with Salmonella typhimurium SL1344.Methods Macrophages RAW 264.7 were infected with Salmonella typhimurium SL1344,and cell samples were collected at 0 h,8 h,and 16 h for RNA-sequencing(RNA-seq).Upstream and downstream analyses of the transcriptome data including differential gene expression,clustering,functional annotation,and mo-lecular network studies were conducted to elucidate the signaling pathways changes in macrophages.Results Infec-ted macrophages exhibited significant morphological and transcriptional changes.Differential gene analysis identified significant upregulation and downregulation patterns.Clustering revealed six gene clusters involving various signaling pathways,such as immune response,membrane transport,and lipid catabolic process.Conclusions Macrophages dynamically respond to Salmonella typhimurium infection,displaying distinct temporal gene expression patterns.The coordinated activation of immune response,membrane transport,and lipid catabolic process pathways implies a multifaceted cellular adaptation to external infections,providing essential insights into the molecular mechanisms of macrophage response to Salmonella typhimurium infection.

Objective To explore the research dynamics and hotspots of project management in the field of hospital man-agement,and analyze the contents that still need to be improved,so as to provide references for the subsequent research,and provide hospital managers with practical experience in hospital management.Methods Based on the PubMed database,we used the citexs data analysis platform to analyze the literature and big data from January 2012 to December 2022 on the application of project management in the field of hospital management.Results The effective literature was retrieved from 4236 articles,and the analysis found thatthe annualnumberofpublicationsinthisfield hasbeenincreasing,2021 sawthe highestannualnumberof 573 articles,and the fastest growth rate was 20.36% in 2017.The country with the most publications is the United States(1 546 articles,36.5% ),the research institution with the most publications is Monash University,Australia,the journal with the most publications is BMJ Open(124 articles),and the key words with the highest frequency of occurrence in the retrieved literature are quality improvement,primary care improvement,covid-19,telemedicine.Conclusion The research in this field has been rapidly developed and is in a fast rising phase.In almost every organization and industry,the share of project management or"projectization"is increasing,and project management has become an important part of hospital management research and prac-tice.In the context of building a modern hospital management system,the application of project management to hospital manage-ment is an effective means of improving the level of fine hospital management.

Objectives:To investigate the impact of baseline non-high-density lipoprotein cholesterol(non-HDL-C)levels on new-onset cardiovascular disease(CVD)in postmenopausal women. Methods:This prospective cohort study selected 8 893 postmenopausal women who participated from 2006 to 2018 employee health examination of Kailuan Group and had complete total cholesterol(TC)and HDL-C data and no history of CVD.Participants were followed up to 31 December,2021.The primary endpoint was the occurrence of CVD or death.According to the Chinese Lipid Management Guidelines(2023),the participants were divided into non-HDL-C<4.1 mmol/L group(n=6 079),4.1 mmol/L≤non-HDL-C<4.9 mmol/L group(n=1 824)and non-HDL-C≥4.9 mmol/L group(n=990).The cumulative incidence of CVD in different groups of non-HDL-C levels was calculated using the Kaplan-Meier method and tested by log-rank analysis.Multivariate Cox regression model was used to analyze the effects of different non-HDL-C levels on CVD. Results:The mean follow-up time was(10.78±4.48)years,the cumulative incidence of CVD in different non-HDL-C level groups was 1.82%,3.24%and 2.89%,respectively.Kaplan-Meier survival curve showed a statistically significant difference in cumulative incidence among the three groups(log-rank P<0.0001).The results of Cox regression analysis showed that after adjusting for confounding factors such as age and sex,the HR(95%CI)values for CVD in the 4.1≤non-HDL-C<4.9 mmol/L group and the non-HDL-C≥4.9 mmol/L group were 1.40(1.13-1.74)and 1.35(1.03-1.78),respectively. Conclusions:High non-HDL-C levels are an independent risk factor for new-onset CVD in postmenopausal women.

Pyroptosis, an inflammatory caspase-dependent programmed cell death, plays a vital role in maintaining tissue homeostasis and activating inflammatory responses. Orthodontic tooth movement (OTM) is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament (PDL) progenitor cells. However, whether and how force induces PDL progenitor cell pyroptosis, thereby influencing OTM and alveolar bone remodeling remains unknown. In this study, we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process. Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively. Using Caspase-1^-/- mice, we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1. Moreover, mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro, which influenced osteoclastogenesis. Mechanistically, transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells. Overall, this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli, indicating a promising approach to accelerate OTM by targeting Caspase-1.
Animals ; Humans ; Mice ; Rats ; Bone Remodeling/physiology* ; Caspase 1 ; Periodontal Ligament ; Pyroptosis ; Tooth Movement Techniques