1.DNA Methyltransferases 1-Regulated Methylation of Protein Kinase C Zeta Influences Its Expression in Breast Cancer Cells
Xixun ZHANG ; Lianglan BAO ; Mengya SUN ; Jinbin CHEN
Journal of Breast Cancer 2025;28(2):72-85
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.
2.DNA Methyltransferases 1-Regulated Methylation of Protein Kinase C Zeta Influences Its Expression in Breast Cancer Cells
Xixun ZHANG ; Lianglan BAO ; Mengya SUN ; Jinbin CHEN
Journal of Breast Cancer 2025;28(2):72-85
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.
3.DNA Methyltransferases 1-Regulated Methylation of Protein Kinase C Zeta Influences Its Expression in Breast Cancer Cells
Xixun ZHANG ; Lianglan BAO ; Mengya SUN ; Jinbin CHEN
Journal of Breast Cancer 2025;28(2):72-85
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.
4.Clinical efficacy and safety of transcatheter aortic valve replacement for patients with severe pure native aortic regurgitation.
Jiantao CHEN ; Yi ZHANG ; Kangni FENG ; Suiqing HUANG ; Hanri XIAO ; Mengya LIANG ; Zhongkai WU
Journal of Zhejiang University. Medical sciences 2025;54(4):529-540
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
5.Epidemic characteristics of measles and efforts to control measles infections in Zhejiang Province, China
Rui YAN ; Mengya YANG ; Hanqing HE ; Yan FENG ; Yang ZHOU ; Xuewen TANG ; Xuan DENG ; Yao ZHU ; Yuxia DU ; Can CHEN ; Cao KEXIN ; Shigui YANG ;
Epidemiology and Health 2024;46(1):e2024075-
OBJECTIVES:
Several countries have successfully eliminated measles, and China is making significant strides toward achieving this goal. This study focused on investigating the patterns of measles infections in Zhejiang Province, China, as well as control measures. The objective was to provide valuable insights that could contribute to the development of nationwide elimination strategies.
METHODS:
We analyzed measles surveillance data from 2005 to 2022 in Zhejiang Province. We utilized a joinpoint regression model to examine trends in measles. Additionally, we employed SaTScan version 9.5 to identify spatial-temporal clusters. Finally, we used an age-period-cohort model to assess the effects of age, period, and cohort.
RESULTS:
The age-standardized incidence rate (ASIR) of measles infection in Zhejiang Province from 2005 to 2022 was 5.24 per 100,000, showing a consistent and significant downward trend with an annual percentage change of -24.93% (p<0.05). After 2020, the ASIR for measles infection fell to below 0.1 per 100,000. The majority of measles cases occurred in individuals either without an immunization history or with an unknown immunization status, representing 41.06% and 41.40% of the cases from 2010 to 2022, respectively. According to data from the National Measles Surveillance System, the annual rate of discarded measles cases from 2009 to 2014, and the annual rate of discarded measles and rubella cases from 2015 to 2022, were both above 2 per 100,000, indicating the high sensitivity of the measles surveillance system.
CONCLUSIONS
The significant reduction in measles incidence from 2005 to 2022 demonstrates substantial progress in Zhejiang Province towards the elimination of measles.
6.Epidemic characteristics of measles and efforts to control measles infections in Zhejiang Province, China
Rui YAN ; Mengya YANG ; Hanqing HE ; Yan FENG ; Yang ZHOU ; Xuewen TANG ; Xuan DENG ; Yao ZHU ; Yuxia DU ; Can CHEN ; Cao KEXIN ; Shigui YANG ;
Epidemiology and Health 2024;46(1):e2024075-
OBJECTIVES:
Several countries have successfully eliminated measles, and China is making significant strides toward achieving this goal. This study focused on investigating the patterns of measles infections in Zhejiang Province, China, as well as control measures. The objective was to provide valuable insights that could contribute to the development of nationwide elimination strategies.
METHODS:
We analyzed measles surveillance data from 2005 to 2022 in Zhejiang Province. We utilized a joinpoint regression model to examine trends in measles. Additionally, we employed SaTScan version 9.5 to identify spatial-temporal clusters. Finally, we used an age-period-cohort model to assess the effects of age, period, and cohort.
RESULTS:
The age-standardized incidence rate (ASIR) of measles infection in Zhejiang Province from 2005 to 2022 was 5.24 per 100,000, showing a consistent and significant downward trend with an annual percentage change of -24.93% (p<0.05). After 2020, the ASIR for measles infection fell to below 0.1 per 100,000. The majority of measles cases occurred in individuals either without an immunization history or with an unknown immunization status, representing 41.06% and 41.40% of the cases from 2010 to 2022, respectively. According to data from the National Measles Surveillance System, the annual rate of discarded measles cases from 2009 to 2014, and the annual rate of discarded measles and rubella cases from 2015 to 2022, were both above 2 per 100,000, indicating the high sensitivity of the measles surveillance system.
CONCLUSIONS
The significant reduction in measles incidence from 2005 to 2022 demonstrates substantial progress in Zhejiang Province towards the elimination of measles.
7.Epidemic characteristics of measles and efforts to control measles infections in Zhejiang Province, China
Rui YAN ; Mengya YANG ; Hanqing HE ; Yan FENG ; Yang ZHOU ; Xuewen TANG ; Xuan DENG ; Yao ZHU ; Yuxia DU ; Can CHEN ; Cao KEXIN ; Shigui YANG ;
Epidemiology and Health 2024;46(1):e2024075-
OBJECTIVES:
Several countries have successfully eliminated measles, and China is making significant strides toward achieving this goal. This study focused on investigating the patterns of measles infections in Zhejiang Province, China, as well as control measures. The objective was to provide valuable insights that could contribute to the development of nationwide elimination strategies.
METHODS:
We analyzed measles surveillance data from 2005 to 2022 in Zhejiang Province. We utilized a joinpoint regression model to examine trends in measles. Additionally, we employed SaTScan version 9.5 to identify spatial-temporal clusters. Finally, we used an age-period-cohort model to assess the effects of age, period, and cohort.
RESULTS:
The age-standardized incidence rate (ASIR) of measles infection in Zhejiang Province from 2005 to 2022 was 5.24 per 100,000, showing a consistent and significant downward trend with an annual percentage change of -24.93% (p<0.05). After 2020, the ASIR for measles infection fell to below 0.1 per 100,000. The majority of measles cases occurred in individuals either without an immunization history or with an unknown immunization status, representing 41.06% and 41.40% of the cases from 2010 to 2022, respectively. According to data from the National Measles Surveillance System, the annual rate of discarded measles cases from 2009 to 2014, and the annual rate of discarded measles and rubella cases from 2015 to 2022, were both above 2 per 100,000, indicating the high sensitivity of the measles surveillance system.
CONCLUSIONS
The significant reduction in measles incidence from 2005 to 2022 demonstrates substantial progress in Zhejiang Province towards the elimination of measles.
8.Changes of pulmonary function of pertussis in children aged 5-17 years
Wei CHEN ; Mengya ZHAO ; Fei XIAO ; Chuanhe LIU
Tianjin Medical Journal 2024;52(10):1075-1078
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.
9.Identification of potential immune-related mechanisms related to the development of multiple myeloma
Yaomei WANG ; Wenli ZHANG ; Tiandong LI ; Mengmeng LIU ; Mengya GAO ; Xinqing LI ; Yufei CHEN ; Yongping SONG ; Wei LI ; Chunyan DU ; Fang WANG ; Lina LIU
Chinese Medical Journal 2024;137(13):1603-1613
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.
10.Exploring the mechanism of action of acupuncture-targeted therapy for rheumatoid arthritis and identifying candidate traditional Chinese medicines
Mengya LI ; Yue CHEN ; Ning CHENG ; Haixin YOU ; Changsong DING
International Journal of Traditional Chinese Medicine 2024;46(6):764-772
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.

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