1.EZH2 promotes malignant biological behavior in esophageal squamous cell carcinoma via EMT.
Yuying JING ; Kaige YANG ; Yiting CHENG ; Tianping HUANG ; Sufang CHEN ; Kai CHEN ; Jianming HU
Journal of Central South University(Medical Sciences) 2025;50(2):155-166
OBJECTIVES:
Esophageal squamous cell carcinoma (ESCC) is characterized by complex pathogenesis and poor prognosis. In recent years, epithelial-mesenchymal transition (EMT) in tumor initiation and progression has attracted increasing attention. Enhancer of zeste homolog 2 (EZH2), which is aberrantly expressed in various tumors, may be closely related to the EMT process. This study aims to examine the expression and correlation of EZH2 and EMT markers in ESCC cells and tissues, evaluate the effects of EZH2 knockdown on ESCC cell proliferation, invasion, and migration, and explore how EZH2 contributes to the malignant biological behavior of ESCC.
METHODS:
Bioinformatics analyses were used to assess EZH2 expression levels in ESCC. Small interfering RNA was used to knock down EZH2 in ESCC cell lines EC109 and EC9706. Cell proliferation, invasion, and migration were evaluated using cell counting kit-8 (CCK-8), wound healing, and Transwell assays. Protein and mRNA expression levels of EZH2, E-cadherin (E-cad), and vimentin (Vim) were detected by Western blotting and real time fluorogenic quantitative PCR (RT-qPCR), respectively. Immunohistochemical (IHC) staining was performed on 70 ESCC tissue samples and 40 paired adjacent normal tissues collected from the First Affiliated Hospital of Shihezi University between 2010 and 2016 to assess the expression of EZH2, E-cad, and Vim, and to analyze their associations with clinicopathological feature and patient prognosis.
RESULTS:
Bioinformatics analysis showed that EZH2 was highly expressed in ESCC (P<0.001), and high EZH2 expression was associated with worse prognosis (P<0.001). CCK-8, wound healing, and Transwell assays demonstrated that EZH2 knockdown significantly suppressed the proliferation, invasion, and migration of ESCC cells (P<0.001). In addition, Vim expression was significantly reduced, while E-cad expression was significantly increased at both protein and mRNA levels in EZH2-silenced cells (all P<0.05). IHC staining analysis revealed higher expression of EZH2 and Vim and lower expression of E-cad in ESCC tissues compared to adjacent normal tissues. Kaplan-Meier survival analysis showed that low expression of EZH2 and Vim and high expression of E-cad were associated with longer survival (all P<0.05).
CONCLUSIONS
EZH2 promotes malignant biological behavior in ESCC by mediating EMT. Elevated EZH2 expression is associated with poor prognosis in ESCC patients.
Humans
;
Enhancer of Zeste Homolog 2 Protein/physiology*
;
Esophageal Squamous Cell Carcinoma/pathology*
;
Epithelial-Mesenchymal Transition/genetics*
;
Esophageal Neoplasms/metabolism*
;
Cell Proliferation
;
Cell Line, Tumor
;
Cell Movement
;
Cadherins/genetics*
;
Vimentin/genetics*
;
Male
;
Female
;
Middle Aged
;
Neoplasm Invasiveness
;
Prognosis
;
RNA, Small Interfering/genetics*
;
Gene Expression Regulation, Neoplastic
2.Structures and functions of the MICOS: Pathogenesis and therapeutic implications in Alzheimer's disease.
Zihan WANG ; Kaige ZHANG ; Minghao HUANG ; Dehao SHANG ; Xiaomin HE ; Zhou WU ; Xu YAN ; Xinwen ZHANG
Acta Pharmaceutica Sinica B 2025;15(6):2966-2984
Mitochondrial dysfunction is a critical factor in the pathogenesis of Alzheimer's disease (AD). The mitochondrial contact site and cristae organizing system (MICOS) plays a pivotal role in shaping the inner mitochondrial membrane, forming cristae junctions and establishing interaction sites between the inner and outer mitochondrial membranes and thereby serving as a cornerstone of mitochondrial structure and function. In the past decade, MICOS abnormalities have been extensively linked to AD pathogenesis. In particular, dysregulated expression of MICOS subunits and mutations in MICOS-related genes have been identified in AD, often in association with hallmark pathological features such as amyloid-β plaque accumulation, neurofibrillary tangle formation, and neuronal apoptosis. Furthermore, MICOS subunits interact with several etiologically relevant proteins, significantly influencing AD progression. The intricate crosstalk between these proteins and MICOS subunits underscores the relevance of MICOS dysfunction in AD. Therapeutic strategies targeting MICOS subunits or their interacting proteins may offer novel approaches for AD treatment. In the present review, we introduce current understanding of MICOS structures and functions, highlight MICOS pathogenesis in AD, and summarize the available MICOS-targeting drugs potentially useful for AD.
3.Promoting Innovative Development of Traditional Chinese Medicine Case Report Based on China Clinical Cases Library of Traditional Chinese Medicine
Kaige ZHANG ; Hongcai SHANG ; Yong ZHU ; Weijun HUANG ; Xiaoxiao ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(6):190-195
China Clinical Cases Library of Traditional Chinese Medicine is built to promote the establishment of a scientific and technological talent evaluation system oriented on innovative value, ability and contribution in the backgroud of breaking the four only and setting new standards required by the document jointly issued by several national administrations and commissions. In the process of the construction, in order to further consolidate the foundation and ensure the quality and authority of case reports, we need to fully understand the origin and development of Chinese medical cases. Therefore, we clarified the development situation of Chinese medical cases by combing the characteristics of ancient and modern case reports, comparing the differences between Chinese and western medical case reports in terms of content and writing requirements, finally formed the main points of systematic case report norms and quality evaluation system, aiming to fully explore the unique advantages of Chinese medical cases in the fields of discipline development, scientific research innovation, clinical practice and guidance, talent evaluation and training, so as to promote its innovative development in a broader direction.
4.Construction and evaluation of a nomogram prognostic model for patients of prostate cancer with high tumor load bone metastases
Xin HUANG ; Yakun HOU ; Ning TAO ; Tao ZHUO ; Aihaiti RENAGULI ; Kaige ZHANG ; Miao YAO ; Hengqing AN
Journal of Modern Urology 2024;29(3):205-211
【Objective】 To identify the risk factors of patients of bone metastatic prostate cancer with high tumor load progressed to castration resistant prostate cancer (CRPC), establish a nomogram prediction model and evaluate its consistency and accuracy. 【Methods】 A total of 164 patients diagnosed by puncture and imaging during 2012 and 2022 were included.The general characteristics were analyzed with IBM SPSS software; the variables were screened with Cox regression; the multivariate risk factors with P<0.05 were included in the nomogram prediction model.The consistency and prediction accuracy of the model were evaluated with C-index, receiver operating characteristic (ROC) curve and calibration chart. 【Results】 In univariate analysis, initial prostate-specific antigen (PSA), prostate-specific antigen density (PSAD), Gleason score, T stage, alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were correlated with CRPC (P<0.05).Multivariate analysis showed that initial PSA, Gleason score, T stage, ALP and LDH were independent risk factors of CRPC (P<0.05).Based on the above five risk factors, a nomogram prediction model was constructed.The C-index was 0.801, the area under ROC curve (AUC) of 1-year progression-free survival (PFS) was 0.701 (0.608-0.794), and the AUC of 2-year PFS was 0.857 (0.767-0.947).The calibration chart showed that the prediction probability of the model was in good agreement with the actual probability. 【Conclusion】 Initial PSA, Gleason score, T stage, ALP and LDH are independent risk factors of CRPC.The predictive model may be an effective tool for the initial diagnosis of high tumor load bone metastatic prostate cancer, but more data are needed for internal and external validation.
5.Promoting Reform of Talent Evaluation Based on China Clinical Cases Library of Traditional Chinese Medicine
Kaige ZHANG ; Yong ZHU ; Jisheng WANG ; Liangzhen YOU ; Weijun HUANG ; Jie YANG ; Candong LI ; Genping LEI ; Chuan ZHENG ; Shuzhen GUO ; Longtao LIU ; Zhining TIAN ; Xinping QIU ; Wenli SU ; Zuo LI ; Wei YAN ; Hongcai SHANG ; Xiaoxiao ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):220-226
Talents are the main force for the development of traditional Chinese medicine(TCM), and the construction of TCM talents and the reformation of talent evaluation system are essential to promote the inheritance and innovation of TCM. At present, we are still exploring and developing in the fields of the formulation, implementation and evaluation indicators of TCM talent evaluation system. However, there are shortcomings and difficulties. For instance, insufficient stratification in the evaluation, excessive emphasis on the quantity of achievements, neglecting the quality of the achievements and the actual contribution, imperfect assessment indicators, and the weak characteristics of TCM. Therefore, national ministries and commissions have jointly issued a document requesting to break the four only and set a new standard, in order to promote the construction of a scientific and technological talent evaluation system oriented by innovation value, ability and contribution. For the evaluation of TCM clinical talents, China Association for Science and Technology commissioned China Association of Chinese Medicine to build the China Clinical Cases Library of TCM(CCCL-TCM), which aims at collecting the most authoritative and representative TCM clinical cases and exploring the advantages of applying clinical cases as masterpiece of achievement in TCM clinical talents evaluation. CCCL-TCM can promote the construction of a talent evaluation system that is more in line with the development characteristics of TCM industry, and to carry out relevant pilot in TCM colleges and institutions across the country in order to promote the reformation of TCM talent evaluation system.
6. Interaction effect and predictive efficacy of blood glucose and blood calcium on the prognosis of patients with acute severe pancreatitis
Kaige HUANG ; Qinhua XU ; Wei WANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(11):1227-1234
AIM: To investigate the interactive effects of blood glucose and blood calcium on the prognostic impact of patients with acute severe pancreatitis (SAP) and to analyze their predictive efficacy on prognosis. METHODS: One hundred and seven patients with SAP admitted to our hospital from September 2019 to October 2022 were selected for the study and were divided into poor and good groups according to their prognosis within 28 d. The blood glucose, blood calcium, modified Marshall score, bedside acute pancreatitis severity score (BISAP) were compared between the two groups before treatment, after 3 d of treatment, and after 7 d of treatment, and the correlation between blood glucose, blood calcium and modified Marshall score and BISAP score was analyzed. The blood glucose levels of patients with different blood calcium were compared. Cox regression was used to analyze the factors associated with prognosis. The presence and type of interaction between blood glucose and blood calcium on prognosis were analyzed using the interaction coefficient γ and relative risk (RR) values. The subject operating characteristic curve (ROC) was used to analyze the predictive efficacy of blood glucose and blood calcium on prognosis. RESULTS: The blood glucose, modified Marshall score, and BISAP score of the adverse group after treatment were higher than those of the good group, while the blood calcium was lower than that of the good group (P<0.05). After 3 and 7 days of treatment, blood glucose was positively correlated with improved Marshall score and BISAP score (P<0.05). The blood glucose level in patients with decreased blood calcium was higher than that in patients with normal blood calcium (P<0.05). The decrease of blood calcium had positive interaction with the increase of blood glucose (P<0.05). After 3 and 7 days of treatment, the AUC of blood glucose combined with blood calcium was greater than that predicted by single index (P< 0.05). CONCLUSION: Blood glucose and blood calcium are related to the severity of the disease in SAP patients. There is an interaction between blood glucose and blood calcium in predicting the prognosis of SAP patients. The combined detection of blood glucose and blood calcium has a certain predictive effect on the prognosis of SAP patients.
7.Clinical characteristics and prognostic factors after percutaneous coronary intervention of women with the first non-ST-segment elevation myocardial infarction
Hong CHEN ; Lu LI ; Kaige FENG ; Lei HUANG ; Ying DIAO ; Qiulin WANG
The Journal of Practical Medicine 2018;34(1):111-114,118
Objective To investigate the clinical characteristics and prognostic factors after percutaneous coronary intervention of women with the first non-ST-segment elevation myoeardial infarction.Methods A total of 123 female patients with AMI,including 70 patients with NSTEMI and 53 patients with ST-segment elevation myocardial infarction (STEMI),who received PCI within 24 hours of onset were selected from June 2013 to June 2015.The clinical data were compared between patients with NSTEMI and with STEMI.Cox regression model was used to analyze the prognostic factors for the elderly patients with NSTEMI.Results The female patients with NSTEMI had more cases of patients with hypertension (48 vs.26),diabetes (38 vs.38) and hyperlipidemia (52 vs.29)than the female patients with STEMI.Significant differences in systolic blood pressure [(134.31±22.26)mmHg vs.(125.04 ± 19.63) mmHg],levels of white blood cell [(9.02 ± 3.75) 109/L vs.(11.37 ± 3.63) 109/L] and troponin Ⅰ [(8.63 ± 18.34) μg/L vs.(18.79 ± 27.76) μg/L] were observed in the above two groups (l P < 0.05,respectively).The rates of revascularization,major adverse cardiovascular events in NSTEMI group were higher than those in STEMI group during 1 year after discharge (47.7% vs.28.0%,62.9% vs.35.8%) (P < 0.05,respectively).Cox survival analysis showed that white blood cell (HR =1.241) and troponin-Ⅰ (HR =1.026) elevation were the risk prognostic factors after PCI for women with the first NSTEMI.Conclusion More hypertension,diabetes,hyperlipidemia and higher levels of systolic blood pressure,lower levels of white blood cell and troponin Ⅰ were observed in women with the first NSTEMI.The long-term prognosis of female patients with NSTEMI is poor.And elevated levels of white blood cell and troponin-Ⅰ were the risk prognostic factors after PCI for women with the first NSTEMI.

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