ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.

Reproductive system diseases are among the primary contributors to the decline in social fertility rates and the intensification of aging, posing significant threats to both physical and mental health, as well as quality of life. Recent research has revealed the substantial potential of the gut microbiota in improving reproductive system diseases. Under healthy conditions, the gut microbiota maintains a dynamic balance, whereas dysfunction can trigger immune-inflammatory responses, metabolic disorders, and other issues, subsequently leading to reproductive system diseases through the gut-gonadal axis. Reproductive diseases, in turn, can exacerbate gut microbiota imbalance. This article reviews the impact of the gut microbiota and its metabolites on both male and female reproductive systems, analyzing changes in typical gut microorganisms and their metabolites related to reproductive function. The composition, diversity, and metabolites of gut bacteria, such as Bacteroides, Prevotella, and Firmicutes, including short-chain fatty acids, 5-hydroxytryptamine, γ-aminobutyric acid, and bile acids, are closely linked to reproductive function. As reproductive diseases develop, intestinal immune function typically undergoes changes, and the expression levels of immune-related factors, such as Toll-like receptors and inflammatory cytokines (including IL-6, TNF-α, and TGF-β), also vary. The gut microbiota and its metabolites influence reproductive hormones such as estrogen, luteinizing hormone, and testosterone, thereby affecting folliculogenesis and spermatogenesis. Additionally, the metabolism and absorption of vitamins can also impact spermatogenesis through the gut-testis axis. As the relationship between the gut microbiota and reproductive diseases becomes clearer, targeted regulation of the gut microbiota can be employed to address reproductive system issues in both humans and animals. This article discusses the regulation of the gut microbiota and intestinal immune function through microecological preparations, fecal microbiota transplantation, and drug therapy to treat reproductive diseases. Microbial preparations and drug therapy can help maintain the intestinal barrier and reduce chronic inflammation. Fecal microbiota transplantation involves transferring feces from healthy individuals into the recipient’s intestine, enhancing mucosal integrity and increasing microbial diversity. This article also delves into the underlying mechanisms by which the gut microbiota influences reproductive capacity through the gut-gonadal axis and explores the latest research in diagnosing and treating reproductive diseases using gut microbiota. The goal is to restore reproductive capacity by targeting the regulation of the gut microbiota. While the gut microbiota holds promise as a therapeutic target for reproductive diseases, several challenges remain. First, research on the association between gut microbiota and reproductive diseases is insufficient to establish a clear causal relationship, which is essential for proposing effective therapeutic methods targeting the gut microbiota. Second, although gut microbiota metabolites can influence lipid, glucose, and hormone synthesis and metabolism via various signaling pathways—thereby indirectly affecting ovarian and testicular function—more in-depth research is required to understand the direct effects of these metabolites on germ cells or granulosa cells. Lastly, the specific efficacy of gut microbiota in treating reproductive diseases is influenced by multiple factors, necessitating further mechanistic research and clinical studies to validate and optimize treatment regimens.

Background The association between occupational physical activity (OPA) and cardiometabolic risk factors remains controversial, potentially due to differences in the associations between OPA and various cardiometabolic indicators, as well as the lack of a clearly defined optimal OPA range for multiple-indicator synergistic benefits. Objective To investigate the relationship between OPA and cardiometabolic risk factors in individuals at high risk of cardiovascular disease (CVD) in Hubei Province, and to explore an optimal OPA range for multi-indicator improvements. Methods Data were derived from the Hubei Province dataset of the China Health Evaluation And Risk Reduction Through Nationwide Teamwork from 2015 to 2023, including 19028 high-risk CVD individuals. OPA (metabolic equivalent·h·d⁻¹, MET·h·d⁻¹) was assessed using the China Kadoorie Biobank physical activity questionnaire, anthropometric measurements (height, weight, waist circumference) and cardiometabolic indicators (blood pressure, fasting blood glucose, lipid profiles) were measured. Multivariate logistic regression was used to analyze the association between logOPA quartiles (Q1-Q4) and abnormal cardiometabolic indicators, while restricted cubic spline (RCS) models were employed to explore their dose-response relationships. Subgroup and interaction analyses were also conducted by gender. Results The median OPA of all participants was 12.86 MET·h·d⁻¹ (male: 14.40 MET·h·d⁻¹, female: 11.14 MET·h·d⁻¹). After adjusting for confounders, compared with the Q1 group, logOPA in the Q4 group was associated with 20% (OR=0.80, 95%CI: 0.72, 0.89), 14% (OR=0.86, 95%CI: 0.78, 0.96), and 13% (OR=0.87, 95%CI: 0.79, 0.95) reduction in the risk of abdominal obesity, low high-density lipoprotein cholesterol (HDL-C), and metabolic syndrome (MS), respectively, and 33% (OR=1.33, 95%CI: 1.18, 1.49), 33% (OR=1.33, 95%CI: 1.18, 1.50), and 38% (OR=1.38, 95%CI: 1.21, 1.57) increase in the risk of high total cholesterol (TC), high low-density lipoprotein cholesterol (LDL-C), and high non-HDL-C, respectively. Similar trends were observed in males and females, with significant positive associations of logOPA with high TC and high non-HDL-C in males (P_interaction<0.05). The risk of low HDL-C decreased rapidly when logOPA was more than 2.213 (OPA>9.14 MET·h·d⁻¹), showing an inverted L-shaped trend. The risk of high TC, high LDL-C, and high non-HDL-C increased beyond logOPA thresholds of 3.244, 2.476, and 3.377 (OPA >25.64, 11.89, and 29.28 MET·h·d⁻¹), respectively, showing a J-shaped trend. However, logOPA exhibited a U-shaped nonlinear dose-response relationship with blood pressure and fasting blood glucose abnormalities (P_non-linear<0.05) , with minimal risks at logOPA 2.969 and 2.372 (OPA of 19.47 and 10.72 MET·h·d⁻¹). Conclusion OPA exhibits heterogeneous dose-response patterns across cardiometabolic indicators. Integrating the inverted L-, J-, and U-shaped association patterns, we suggest an optimal OPA range of 9.14−25.64 MET·h·d⁻¹ for multiple cardiometabolic indicators in total individuals at high-risk of CVD, with ranges of 9.61−31.34 MET·h·d⁻¹ for males and 8.97−22.87 MET·h·d⁻¹ for females. These findings provide critical evidence for developing OPA interventions strategies targeting high-risk population for CVD.

Background::Understanding willingness to undergo pulmonary function tests (PFTs) and the factors associated with poor uptake of PFTs is crucial for improving early detection and treatment of chronic obstructive pulmonary disease (COPD). This study aimed to understand willingness to undergo PFTs among high-risk populations and identify any barriers that may contribute to low uptake of PFTs.Methods::We collected data from participants in the "Happy Breathing Program" in China. Participants who did not follow physicians’ recommendations to undergo PFTs were invited to complete a survey regarding their willingness to undergo PFTs and their reasons for not undergoing PFTs. We estimated the proportion of participants who were willing to undergo PFTs and examined the various reasons for participants to not undergo PFTs. We conducted univariable and multivariable logistic regressions to analyze the impact of individual-level factors on willingness to undergo PFTs.Results::A total of 8475 participants who had completed the survey on willingness to undergo PFTs were included in this study. Out of these participants, 7660 (90.4%) were willing to undergo PFTs. Among those who were willing to undergo PFTs but actually did not, the main reasons for not doing so were geographical inaccessibility ( n = 3304, 43.1%) and a lack of trust in primary healthcare institutions ( n = 2809, 36.7%). Among the 815 participants who were unwilling to undergo PFTs, over half ( n = 447, 54.8%) believed that they did not have health problems and would only consider PFTs when they felt unwell. In the multivariable regression, individuals who were ≤54 years old, residing in rural townships, with a secondary educational level, with medical reimbursement, still working, with occupational exposure to dust, and aware of the abbreviation "COPD" were more willing to undergo PFTs. Conclusions::Willingness to undergo PFTs was high among high-risk populations. Policymakers may consider implementing strategies such as providing financial incentives, promoting education, and establishing community-based programs to enhance the utilization of PFTs.

Aim To investigate the changes in the proliferation and apoptosis of Siha cells after knocking down Rho GTPase-activating protein 30(ARHGAP30).Methods After designing specific shARHGAP30 primers and connecting them to the pLKO.1 vector,we transformed them into Escherichia coli competent cells,then co-transfecting them with lentiviral helper plasmids into HEK-293T cells.We collected and filtered cell supernatant to obtain the vi-rus to infect Siha cells.RT-qPCR and Western blot were used to detect knockdown efficiency,as well as changes in the expression of Bax and Bcl-2 after trans-fection.The CCK-8 method was employed to measure the proliferation level of cells after knockdown.Results After successful construction of a lentiviral plasmid with knockdown of the ARHGAP30 gene and establish-ment of stably transfected Siha cells,ARHGAP30 tran-scription and translation(P＜0.01)in Siha cells de-creased,Bax/Bcl-2 significantly decreased(P＜0.01),indicating decreased apoptosis and increased cell proliferation(P＜0.01).Conclusions This study suggests the involvement of ARHGAP30 in the proliferation and apoptosis of Siha cells,and regulating the ARHGAP30 gene may interfere with the occurrence and development of cervical cancer.

The implementation of amplicon sequencing and metagenomic sequencing methods in the whole-genome sequen-cing for MPXV testing was compared,to provide a technical reference for sequencing,tracing,and epidemic prevention and control of MPXV.For amplicon sequencing,targeted amplification of the viral whole genome was performed on MPXV DNA,and was followed by next-generation sequencing of the amplification products.For metagenomic sequencing,next-generation sequencing was performed directly on MPXV DNA.After the sequences were obtained,software such as CLC and IGV were used to analyze the effective data percentage,sequencing depth,and whole-genome sequencing coverage under different sequen-cing depths for both sequencing methods,to evaluate sequencing quality.Nextclade was used to analyze virus typing,muta-tions,and deletions.Subsequently,the similarity and completeness of sequences obtained through both sequencing methods were further compared.On the basis of mapping to the refer-ence sequence of strain MPXV-M5312_HM12_Rivers(Gen-Bank number NC_063383.1),the percentage effective data obtained from amplicon sequencing and metagenomic sequen-cing was 99.72％and 7.54％,respectively,with a sequencing depth range of 0× to 334 839 ×,and 44 × to 1 000 ×.On the basis of a sequencing depth of 10 ×,the site coverage of the above was 90.3％and 100％,respectively.IGV was used to validate the whole-genome coverage under different sequencing depths.The depth coverage of whole-genome sites for metagenomic sequencing was uniform,whereas that of the whole-genome sites for amplicon sequencing was uneven and significantly differed.Virus typing and sequence similarity analysis indicated that the viral sequences obtained with the two sequencing methods all belonged to the Ⅱb B.1 lineage of MPXV.Comparison with the reference sequence indicated that metagenomic sequencing identified 73 nucleotide mutation sites,whereas amplicon sequen-cing identified 68 mutation sites.Further analysis demonstrated that seven common mutation sites of Ⅱb B.1 were not detected in the amplicon sequencing,and two false positive private mutation sites were identified.Amplicon or metagenomic sequencing methods thus can be flexibly used in MPXV virus whole-genome sequencing.Amplicon sequencing yields more effective data,whereas metagenomic sequencing provides better uniformity of coverage and sequence accuracy.This study provides a prelimi-nary understanding of the efficacy of each method and may serve as a technical reference for improving the success rate of whole-genome sequencing of MPXV.

Loganin(LOG),a bioactive compound derived from Cornus officinalis Siebold & Zucc,has been understudied in the context of osteoarthritis(OA)treatment.In this study,we induced an inflammatory response in chondrocytes using lipopolysaccharide(LPS)and subsequently treated these cells with LOG.We employed fluorescence analysis to quantify reactive oxygen species(ROS)levels and measured the expression of NLRP3 and nuclear factor erythropoietin-2-related factor 2(NRF2)using real-time quantitative polymerase chain reaction(qRT-PCR),Western blotting,and immunofluorescence(IF)techniques.Additionally,we developed an OA mouse model by performing medial meniscus destabilization(DMM)surgery and monitored disease progression through micro-com-puted tomography(micro-CT),hematoxylin and eosin(H&E)staining,safranin O and fast green(S&F)staining,and immunohisto-chemical(IHC)analysis.Our results indicate that LOG significantly reduced LPS-induced ROS levels in chondrocytes,inhibited the activation of the NLRP3 inflammasome,and enhanced NRF2/heme oxygenase 1(HO-1)signaling.In vivo,LOG treatment mitigated cartilage degradation and osteophyte formation triggered by DMM surgery,decreased NLRP3 expression,and increased NRF2 expres-sion.These findings suggest that LOG has a protective effect against OA,potentially delaying disease progression by inhibiting the ROS-NLRP3-IL-1β axis and activating the NRF2/HO-1 pathway.

Objective:This study aims to develop a validated instrument for assessing the degree of integration perceived by patients in the services provided by general practitioner(GP)teams,and to evaluate the current state of integrated medical-prevention services.Methods:The survey tool was initially created through a review of existing literature and semi-structured interviews.It was subsequently refined and enhanced following consultations with experts.The utility of the instrument was confirmed through empirical research,which also facilitated an analysis of the status quo regarding the integration of medical and prevention services.Results:The devised instrument encompasses 18 items distributed across six dimensions:service comprehensiveness,service continuity,depth of service,continuity of relationship,patient-centricity,and service coordination.The cumulative score reflecting patients'perception of the integration level in GP teams'medical-prevention services was 54.30±12.45.Conclusion:The survey instrument developed in this research is characterized by its rationality,novelty,and practical relevance.It offers a patient-centered perspective for assessing the quality of integrated medical and prevention services for primary chronic diseases.While the overall perception of integration among patients is positive,there is a notable deficiency in the depth of services provided.There is a need for optimization of the service process,clarification of the service path,refinement of service management,and development of an integrated incentive mechanism for medical and preventive care,aiming for a deeper integration between medical services and preventive care.

Alzheimer's disease (AD) is a progressive neurodegenerative disease, and in-depth study of its pathogenesis to enable early diagnosis of the disease, as well as identification of potential therapeutic targets, are the current research priority. Cerebrovascular dysfunction is considered to be an important pathophysiological mechanism in AD. Neurovascular coupling, which serves as a bridge between neural activity and vascular response, has emerged as a new frontier in the study of cerebrovascular dysfunction in AD. It provides a new perspective to reveal the correlation between vascular pathology and AD. This article reviewd and summarized existing research on changes in cerebral blood perfusion and neural electrical activity across the AD continuum, using various imaging techniques to assess neurovascular coupling. The results indicate that compensatory mechanisms in cerebral blood perfusion can be observed in AD using multiple imaging techniques, and reductions in cerebral blood perfusion and neural electrical activity correlate with the deterioration of cognitive function. Neurovascular coupling indicators derived from multimodal imaging demonstrate good sensitivity and specificity in distinguishing healthy individuals from patients with varying degrees of cognitive impairment, holding promise as effective imaging biomarkers for assessing AD.

Objective:To evaluate the efficiency of the four domestic language models,ERNIE Bot,ChatGLM2,Spark Desk and Qwen-14B-Chat,all with a massive user base and significant social attention,in response to consultations about PCa-related perio-perative nursing and health education.Methods:We designed a questionnaire that includes 15 questions commonly concerned by patients undergoing radical prostatectomy and 2 common nursing cases,and inputted the questions into each of the four language models for simulation consultation.Three nursing experts assessed the model responses based on a pre-designed Likert 5-point scale in terms of accuracy,comprehensiveness,understandability,humanistic care,and case analysis.We evaluated and compared the performance of the four models using visualization tools and statistical analyses.Results:All the models generated high-quality texts with no mis-leading information and exhibited satisfactory performance.Qwen-14B-Chat scored the highest in all aspects and showed relatively sta-ble outputs in multiple tests compared with ChatGLM2.Spark Desk performed well in terms of understandability but lacked comprehen-siveness and humanistic care.Both Qwen-14B-Chat and ChatGLM2 demonstrated excellent performance in case analysis.The overall performance of ERNIE Bot was slightly inferior.All things considered,Qwen-14B-Chat was superior to the other three models in con-sultations about PCa-related perioperative nursing and health education.Conclusion:In PCa-related perioperative nursing,large language models represented by Qwen-14B-Chat are expected to become powerful auxiliary tools to provide patients with more medical expertise and information support,so as to improve the patient compliance and the quality of clinical treatment and nursing.