Purpose: Breast cancer (BC) is a predominant malignancy globally, surpassing lung cancer in terms of diagnostic frequency, with an escalating incidence rate in recent decades.Recent studies have investigated the role of protein kinase C zeta (PRKCZ) in diverse cellular processes in cancer biology. In this study, we evaluated the association between PRKCZ and deleterious outcomes in BC and elucidated the mechanisms underlying its expression in breast carcinoma. Methods: The correlation between PRKCZ and survival rates of patients with BC was investigated using The Cancer Genome Atlas database. The methylation status of the PRKCZ promoter was analyzed using the UALCAN database. Furthermore, we investigated the mechanisms underlying PRKCZ inactivation in BC by treatment with transferase inhibitors, methylation-specific polymerase chain reaction (PCR) analysis, western blotting, and luciferase reporter gene assays. The degree of methylation and expression levels of PRKCZ, as regulated by DNA methyltransferase 1 (DNMT1), were quantified using quantitative PCR and western blotting. Results: Our analysis revealed that decreased expression of PRKCZ in BC was significantly correlated with poor clinical prognosis. Furthermore, we observed that hypermethylation of the PRKCZ promoter contributed to its reduced expression in BC. Notably, DNMT1 has been identified as a critical regulator of PRKCZ methylation. Conclusion Our findings elucidate the tumor-suppressive function of PRKCZ and provide insights into the molecular mechanisms underlying its downregulation in BC.

Purpose: Breast cancer (BC) is a predominant malignancy globally, surpassing lung cancer in terms of diagnostic frequency, with an escalating incidence rate in recent decades.Recent studies have investigated the role of protein kinase C zeta (PRKCZ) in diverse cellular processes in cancer biology. In this study, we evaluated the association between PRKCZ and deleterious outcomes in BC and elucidated the mechanisms underlying its expression in breast carcinoma. Methods: The correlation between PRKCZ and survival rates of patients with BC was investigated using The Cancer Genome Atlas database. The methylation status of the PRKCZ promoter was analyzed using the UALCAN database. Furthermore, we investigated the mechanisms underlying PRKCZ inactivation in BC by treatment with transferase inhibitors, methylation-specific polymerase chain reaction (PCR) analysis, western blotting, and luciferase reporter gene assays. The degree of methylation and expression levels of PRKCZ, as regulated by DNA methyltransferase 1 (DNMT1), were quantified using quantitative PCR and western blotting. Results: Our analysis revealed that decreased expression of PRKCZ in BC was significantly correlated with poor clinical prognosis. Furthermore, we observed that hypermethylation of the PRKCZ promoter contributed to its reduced expression in BC. Notably, DNMT1 has been identified as a critical regulator of PRKCZ methylation. Conclusion Our findings elucidate the tumor-suppressive function of PRKCZ and provide insights into the molecular mechanisms underlying its downregulation in BC.

Purpose: Breast cancer (BC) is a predominant malignancy globally, surpassing lung cancer in terms of diagnostic frequency, with an escalating incidence rate in recent decades.Recent studies have investigated the role of protein kinase C zeta (PRKCZ) in diverse cellular processes in cancer biology. In this study, we evaluated the association between PRKCZ and deleterious outcomes in BC and elucidated the mechanisms underlying its expression in breast carcinoma. Methods: The correlation between PRKCZ and survival rates of patients with BC was investigated using The Cancer Genome Atlas database. The methylation status of the PRKCZ promoter was analyzed using the UALCAN database. Furthermore, we investigated the mechanisms underlying PRKCZ inactivation in BC by treatment with transferase inhibitors, methylation-specific polymerase chain reaction (PCR) analysis, western blotting, and luciferase reporter gene assays. The degree of methylation and expression levels of PRKCZ, as regulated by DNA methyltransferase 1 (DNMT1), were quantified using quantitative PCR and western blotting. Results: Our analysis revealed that decreased expression of PRKCZ in BC was significantly correlated with poor clinical prognosis. Furthermore, we observed that hypermethylation of the PRKCZ promoter contributed to its reduced expression in BC. Notably, DNMT1 has been identified as a critical regulator of PRKCZ methylation. Conclusion Our findings elucidate the tumor-suppressive function of PRKCZ and provide insights into the molecular mechanisms underlying its downregulation in BC.

OBJECTIVES: To evaluate the early clinical efficacy and safety of trans-catheter aortic valve replacement (TAVR) for patients with severe pure native aortic regurgitation (PNAR) who are not suitable for conventional surgical aortic valve replace-ment. METHODS: A retrospective analysis was conducted on 48 patients with PNAR who underwent TAVR at the Department of Cardiac Surgery, the First Affiliated Hospital of Sun Yat-sen University between March 2019 and February 2025. These included 25 cases with transfemoral approach (TF-TAVR group) and 23 cases with transapical approach (TA-TAVR group). Efficacy and safety were assessed by analyzing baseline characteristics, all-cause mortality, and procedure-related complications. RESULTS: Compared with the TA-TAVR group, the TF-TAVR group exhibited significantly smaller aortic annulus circumference and diameter, left ventricular outflow tract circumference and diameter, diameters of the left, right, and non-coronary sinuses, and sinotubular junction (STJ) diameter, along with a shorter distance from the STJ to the aortic annular plane ring plane, a smaller annulus angle (all P<0.05). Additionally, the TF-TAVR group showed a deeper prosthesis implantation depth relative to the aortic annular plane (P<0.01). The overall technical success rate was 91.67%, and the device success rate was 83.33%. Post-TAVR, both groups demonstrated significant improvement in left ventricular end-diastolic diameter (both P<0.05), while only the TA-TAVR group showed significant reduction in left ventricular end-systolic diameter (P<0.05). For primary outcomes, in-hospital mortality occurred in 2 patients (4.17%). No additional deaths were reported at 60 or 90 d after surgery. During 90-180 d after surgery, one patient in the TF-TAVR group died of sudden cardiac death, and one in the TA-TAVR group died of gastroin-testinal bleeding. During 180 d-1 year after surgery, one patient in the TF-TAVR group died of low cardiac output syndrome. No statistically significant differences were observed in 1-year Kaplan-Meier survival curves between the two groups (P>0.05). No conduction block events occurred in TA-TAVR group during hospitalization or 1-year follow-up, while high-grade atrioventricular block, left bundle branch block, permanent pacemaker implantation occurred in TF-TAVR group during hospitalization (12.00%, 4.00%, and 12.00%, respectively). CONCLUSIONS TAVR demonstrates high feasibility and acceptable safety for severe PNAR patients who are not suitable for conventional SAVR. Both TF-TAVR and TA-TAVR show comparable early postoperative efficacy and safety profiles.
Humans ; Transcatheter Aortic Valve Replacement/adverse effects* ; Aortic Valve Insufficiency/surgery* ; Retrospective Studies ; Male ; Female ; Aged ; Treatment Outcome ; Aortic Valve/surgery* ; Aged, 80 and over ; Heart Valve Prosthesis

Objective To evaluate the association between self-reported neighborhood walkability environments and mortality in China.Methods The Prospective Urban Rural Epidemiology study in China(PURE-China)recruited 47 931 participants aged 35-70 from 12 provinces in China between 2005 and 2009.Neighborhood environmental indicators were collected using the Neighborhood Environment Walkability Scale(NEWS)questionnaire,with higher scores indicating better walkable environments.The primary outcomes were all-cause mortality and cardiovascular mortality,using Cox fragile model to evaluate the association between community walkability and outcomes,as well as exploring mediating pathways.Results Of 35 490 participants included in this study,60%were female,with a mean(SD)age of 51.5(9.6)years.The median follow-up was 11.7 years.This study found an association between higher community walkability score and reduced risk of all-cause mortality,with the total score(HR=0.85;95%CI,0.80-0.89),land-use mix(HR=0.84;95%CI,0.79-0.88),and crime safety(HR=0.84;95%CI,0.80-0.89)showing the most significant associations.NEWS can affect long-term adverse outcomes through lifestyle.Conclusions In the Chinese population,favorable community walkability is associated with lower all-cause mortality risk,which may support policymakers to take actions to mitigate the adverse effects of poor community en-vironments on health.

Objective:The association between air pollutants and the risk of sudden cardiac death (SCD) remains controversial. This study aimed to investigate the relationship between five air pollutants—PM 2.5, PM 2.5–10, PM 10, NO 2, and NO?—and the risk of SCD. Methods:We analyzed data from 460 862 participants in the UK Biobank cohort, all enrolled between 2006 and 2010, with no baseline SCD. Follow-up continued until the study endpoint. Annual average concentrations of the five pollutants were assessed. Associations between pollutants and SCD were evaluated using Cox proportional hazards models, followed by Mendelian randomization (MR) to assess causality.Results:Over a mean follow-up of 12.4 years, 2 662 SCD cases were recorded. After adjusting for confounders, no significant associations were found between air pollutants and SCD risk: PM 2.5 ( HR 1.03, 95% CI 0.99–1.07, P = 0.14), PM 2.5–10 ( HR 1.04, 95% CI 1.00–1.08, P = 0.08), PM 10 ( HR 1.01, 95% CI 0.99–1.03, P = 0.26), NO? ( HR 1.00, 95% CI 0.99–1.00, P = 0.26), and NO x ( HR 1.00, 95% CI 1.00–1.01, P = 0.19). MR analysis further supported the absence of causal relationships: PM 2.5 ( β = -0.149, P = 0.90), PM 2.5–10 ( β = 0.387, P = 0.62), PM 10 ( β = -0.994, P = 0.62), NO? ( β = –0.005, P = 0.99), and NO 2 ( β = –0.827, P = 0.25). Conclusions:This study found no evidence linking PM 2.5, PM 2.5–10, PM 10, NO?, or NO 2 to an increased risk of SCD. Mendelian randomization confirmed the lack of causal associations between these pollutants and SCD.

Background::Although significant advances have been made in the treatment of multiple myeloma (MM), leading to unprecedented response and survival rates among patients, the majority eventually relapse, and a cure remains elusive. This situation is closely related to an incomplete understanding of the immune microenvironment, especially monocytes/macrophages in patients with treatment-na?ve MM. The aim of this study was to provide insight into the immune microenvironment, especially monocytes/macrophages, in patients with treatment-na?ve MM.Methods::This study used the single-cell RNA sequencing (scRNA-seq) data of both patients with MM and heathy donors to identify immune cells, including natural killer (NK) cells, T cells, dendritic cells (DCs), and monocytes/macrophages. Transcriptomic data and flow cytometry analysis of monocytes/macrophages were used to further examine the effect of monocytes/macrophages in treatment-na?ve MM patients.Results::A significant difference was observed between the bone marrow (BM) immune cells of the healthy controls and treatment-na?ve MM patients through scRNA-seq. It is noteworthy that, through an scRNA-seq data analysis, this study found that interferon (IFN)-induced NK/T cells, terminally differentiated effector memory (TEMRA) cells, T-helper cells characterized by expression of IFN-stimulated genes (ISG +Th cells), IFN-responding exhausted T cells, mannose receptor C-type 1 (MRC1) + DCs, IFN-responding DCs, MHCII + DCs, and immunosuppressive monocytes/macrophages were enriched in patients with treatment-na?ve MM. Significantly, transcriptomic data of monocytes/macrophages demonstrated that "don’t eat me" -related genes and IFN-induced genes increase in treatment-na?ve MM patients. Furthermore, scRNA-seq, transcriptomic data, and flow cytometry also showed an increased proportion of CD16 + monocytes/macrophages and expression level of CD16. Cell-cell communication analysis indicated that monocytes/macrophages, whose related important signaling pathways include migration inhibitory factor (MIF) and interleukin 16 (IL-16) signaling pathway, are key players in treatment-na?ve MM patients. Conclusions::Our findings provide a comprehensive and in-depth molecular characterization of BM immune cell census in MM patients, especially for monocytes/macrophages. Targeting macrophages may be a novel treatment strategy for patients with MM.

Objective:Exploration on the mechanism of acupuncture-targeted therapy for rheumatoid arthritis and identification of candidate Chinese materia medica.Methods:Targets of acupuncture for RA were collected from related literature, and GSE205962 gene chips were obtained from GEO database. The weighted co-expression network (WGCNA) was constructed by screening differentially expressed genes using R 4.3.1. The collection targets were taken to intersect with the differential genes, and the common genes were obtained for high-throughput GO and KEGG enrichment. The Hub genes were screened by constructing protein interaction networks using the String database and Cytoscape 3.9.0 software. The CIBERSORT algorithm was used to explore the mechanisms of RA immune infiltration, and finally the Coremine Medical database was applied to predict Chinese materia medica.Results:A total of 8 key targets were selected (RHOA, JAK1, FYN, LCK, STAT1, STAT3, EGF, GATA3). The results of immune infiltration analysis showed that various immune cells were closely related to the biological processes of rheumatoid arthritis, including γδ T cells, monocytes, regulatory T cells, CD8 T cells, etc. Saposheikovize Radix, Cinnamomi Ramulus, Anemarrhenae Rhizoma, Dendrobii Caulis, Rehmannine Radix, Lonicerae Japonicae Flos, Pinelliae Rhizoma, Cimicifugae Rhizoma, Poria, Stephaniae Tetrandrae Radix were the 10 kinds of commonly used key Chinese materia medica in the treatment of RA.Conclusions:Acupuncture and moxibustion may treat RA by regulating RHOA, JAK1, FYN, LCK and other core targets. This study predicts that Chinese materia medica can be used as a source of drugs for the treatment of RA, and can provide new ideas for the combination of acupuncture and medicine for the treatment of RA.

Objective To investigate the characteristics of pulmonary function changes in older children with pertussis.Methods Clinical data and pulmonary function date of older children diagnosed with pertussis in outpatient clinics from April 2021 to December 2023 were collected.The clinical data of the case group were collected.A group of healthy older children were included as the control group.Pulmonary function parameters included peak expiratory flow(PEF),forced expiratory volume in the first second(FEV1),forced vital capacity(FVC),FEV1/FVC,expiratory flow at 50%of vital capacity(FEF50),maximum mid-expiratory flow(MMEF)and expiratory flow rate with 75%vigorous exhalation(FEF75).Results Seventy children(36 boys and 34 girls)with pertussis were recruited in the case group,including 54 children with pertussis only and 16 children with pertussis and asthma together.The incidence of paroxysmal cough was 40.0%(28/70)and inspiratory croup 8.5%(6/70)in the case group.Sixty healthy children(28 boys and 32 girls)were included in the control group.There were no significant differences in gender,age,height and body weight between children with pertussis alone group and the control group(P＞0.05).The pulmonary function parameters were significantly lower in the children with pertussis alone group than those in the control group,and PEF had the most obvious decline:PEF%pred[80.5(62.6,85.9)vs.109.8(103.2,118.7)].Compared with the pertussis alone group,pulmonary function was not decrease further in the pertussis combined with asthma group.After the improvement of clinical symptoms of children in the pertussis alone group,the level of pulmonary function(PEF and FEF50)increased significantly,but they were still lower than those of the control group.Conclusion The pulmonary function declines slightly in loder children with pertussis.The decreased PEF is most significant.

Nowadays,the one hospital with multiple districts has become a common model for the development of large public hospitals at present.Through the analysis of the common problems in the development of one hospital with multiple districts,the homogeneous management of one hospital with multiple districts has practical problems,it reflected in difficulties in space management,difficulties,difficulties in staff management,difficulties in system management,difficulties in collaborative development of medical service,difficulties in assessment,difficulties in cost management,difficulties in culture integrations.The case of the scientific management of one hospital with multiple districts in a tertiary public hospitals of provincial state-owned is analyzed,the experience are summarized in terms of organizational structure level,development orientation level,personnel level,performance pay level,cost control level,basic facilities level,culture level,to expected to provide references for promoting the construction of one hospital with multiple districts in public hospitals.