1.COPB1 promotes the development and progression of esophageal squamous cell carcinoma by activating the PI3K/AKT pathway and regulating the tumor immune microenvironment
LIN Yan ; YU Shuangjian ; JIA Sifan ; LI Feiyu ; ZHAO Chenpu ; DONG Zhiming ; SHEN Supeng ; LIANG Jia ; GUO Yanli
Chinese Journal of Cancer Biotherapy 2025;32(12):1236-1246
[摘 要] 目的:探究包被蛋白复合体β1亚基(COPB1)在食管鳞状细胞癌(ESCC)中的表达,及其对ESCC细胞恶性生物学行为的影响、作用机制及临床意义。方法:采用2014~2018年间在河北医科大学第四医院生物样本库中82例ESCC组织及癌旁组织,常规培养正常食管鳞状上皮细胞HEEC和食管癌细胞KYSE-150、KYSE-170、Eca109、TE1、KYSE-30、KYSE-450,用转染试剂将pcDNA3.1-vector(空载体)、pcDNA3.1-COPB1载体,si-NC和si-COPB1转染至KYSE-150、TE1细胞中,记为NC、COPB1-OE、si-NC和si-COPB1组。用数据库数据分析COPB1 mRNA在泛癌组织中的表达及其表达与免疫细胞浸润的关系,qPCR法检测ESCC组织和细胞中COPB1、PIK3CB、CD68、CD163、CD206、ARG1、IL-10 mRNA水平表达情况,WB法检测ESCC组织和各组细胞中的COPB1、PI3K、CD68、CD163、CD206、p-AKT蛋白表达,克隆形成实验和MTS实验检测各组细胞的增殖能力,划痕愈合实验和Transwell实验检测各组细胞的迁移和侵袭能力,免疫组织化学染色(IHC)法检测ESCC组织中COPB1和CD206蛋白表达。以人单核细胞白血病细胞(THP-1)构建巨噬细胞模型,用佛波酯(PMA)和IL-3和IL-4和ESCC细胞上清液诱导巨噬细胞转型,用qPCR和WB法检测CD68和CD206m RNA和蛋白的表达。结果:COPB1在泛癌组织和ESCC组织中均呈高表达且与淋巴结转移和TNM分期有关联(均P < 0.01),COPB1高表达的ESCC患者总生存期短(P < 0.05),COPB1是潜在的ESCC的诊断标志物。COPB1在KYSE-150和TE1细胞中也呈高表达(均P < 0.05),过表达或敲减COPB1可明显抑制或促进KYSE-150和TE1细胞的增殖能力、迁移和侵袭能力(均P < 0.05)。COPB1表达变化诱导的差异表达基因主要富集于PI3K/AKT通路(均P < 0.001), COPB1可促进PI3K/AKT通路的活化(P < 0.05),COPB1高表达可导致M2型巨噬细胞浸润增加(P < 0.05),COPB1高表达促进TAM/M2极化(P < 0.05)。结论:COPB1在ESCC组织中呈高表达,其可激活PI3K/AKT通路及调控肿瘤免疫微环境促进 ESCC发生发展,COPB1有望成为ESCC诊断和预后的生物标志物及治疗靶点。
2.Drug discovery of sclerostin inhibitors.
Sifan YU ; Dijie LI ; Ning ZHANG ; Shuaijian NI ; Meiheng SUN ; Luyao WANG ; Huan XIAO ; Dingdong LIU ; Jin LIU ; Yuanyuan YU ; Zongkang ZHANG ; Samuel Tin Yui YEUNG ; Shu ZHANG ; Aiping LU ; Zhenlin ZHANG ; Baoting ZHANG ; Ge ZHANG
Acta Pharmaceutica Sinica B 2022;12(5):2150-2170
Sclerostin, a protein secreted from osteocytes, negatively regulates the WNT signaling pathway by binding to the LRP5/6 co-receptors and further inhibits bone formation and promotes bone resorption. Sclerostin contributes to musculoskeletal system-related diseases, making it a promising therapeutic target for the treatment of WNT-related bone diseases. Additionally, emerging evidence indicates that sclerostin contributes to the development of cancers, obesity, and diabetes, suggesting that it may be a promising therapeutic target for these diseases. Notably, cardiovascular diseases are related to the protective role of sclerostin. In this review, we summarize three distinct types of inhibitors targeting sclerostin, monoclonal antibodies, aptamers, and small-molecule inhibitors, from which monoclonal antibodies have been developed. As the first-in-class sclerostin inhibitor approved by the U.S. FDA, the monoclonal antibody romosozumab has demonstrated excellent effectiveness in the treatment of postmenopausal osteoporosis; however, it conferred high cardiovascular risk in clinical trials. Furthermore, romosozumab could only be administered by injection, which may cause compliance issues for patients who prefer oral therapy. Considering these above safety and compliance concerns, we therefore present relevant discussion and offer perspectives on the development of next-generation sclerostin inhibitors by following several ways, such as concomitant medication, artificial intelligence-based strategy, druggable modification, and bispecific inhibitors strategy.
3.Study on the value of different diagnostic/classification criteria for the diagnosis of Takayasu's arteritis
Sifan WU ; Lili MA ; Huiyong CHEN ; Wensu YU ; Zhenqi DING ; Yan YAN ; Rongyi CHEN ; Yun LIU ; Lindi JIANG
Chinese Journal of Rheumatology 2021;25(11):727-732
Objective:To compare the diagnostic efficacy of Chinese diagnostic model, the 1990 American College of Rheumatology (ACR) classification criteria and the 2018 ACR new classification criteria (draft) for Takayasu arteritis (TA).Methods:A total of 196 TA patients who came to our hospital from January 1, 2009 to May 31, 2019 in the TA database of the department of rheumatology and immunology, Zhongshan Hospital, Fudan University and 131 patients with other vascular diseases visited during the same period were selected. General characteristics, clinical data, laboratory tests and imaging tests of all patients were collected. Categorical variables were presented as numbers and percentages, between-group differences were analyzed using the χ2 test. Continuous variables were presented as the Mean± SD for a normal distribution or median and interquartile range (IQR) for a non-normal distribution. Between-group differences were analyzed using the Student's t-test or Mann- Whitney test, as appropriate. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy and receiver operating characteristics of the above diagnostic/classification criteria area under the curve were analyzed. P<0.05 was considered significant. Results:In terms of sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and area under receiver operating characteristic curve (ROC), Chinese diagnostic models was 85.7%, 96.2%, 89.9%, 97.1%, 81.5%, 0.909, 1990 ACR criteria was 47.4%, 97.7%, 67.6%, 96.9%, 55.4%, 0.726, 2018 ACR classification criteria was 79.1%, 98.5%, 86.5%, 98.7%, 75.9%, 0.888. The difference between the Chinese diagnostic model and the 2018 ACR criteria in AUC was not statistically significant ( Z=1.186 , P>0.05). The sensitivity, accuracy and diagnostic efficiency of Chinese diagnostic model was the best, that of the 1990 ACR classification criteria was the worst, and the specificity of the 2018 ACR classification criteria was the highest. The Kappa value of the 2018 ACR classification criteria and the Chinese diagnostic model was 0.719, which had good consistency, and the Kappa value of the consistency between the 1990 ACR classification criteria and the Chinese TA diagnostic model was 0.516. Conclusion:The Chinese diagnostic model, which is based on the clinical characteristics of the Chinese TA population, has a good diagnostic efficacy for the Chinese population. The 2018 ACR classification criteria (draft) is highly consistent with the Chinese TA diagnostic model, and can be promoted and applied in practice.
4.Clinical significance of PCT,DD,and CRP levels in patients with infection in acute-on-chronic liver fail-ure
Liming TAN ; Yimei MENG ; Tingting LONG ; Xiaolin GUAN ; Sifan WU ; Wei ZHENG ; Huiying FU ; Qiaohua WANG ; Yang WU ; Tingting ZENG ; Yongjian TIAN ; Jianlin YU ; Juanjuan CHEN ; Hua LI ; Lip-Ing CAO ; Hui XU
The Journal of Practical Medicine 2018;34(3):410-415
Objective To investigate the clinical diagnostic value of serum procalcitonin(PCT),D-dimer (DD),C-reactive protein(CRP)in acute-on-chronic liver failure(ACLF). Methods 124 ACLF patients, 63 chronic hepatitis B patients,32 chronic hepatitis C patients,24 chronic hepatitis E patients and 60 healthy controls from the second affiliated hospital of Nanchang University were enrolled in this study.PCT was detected by a sandwish immunodetection method. D-dimer was detected by Latex Turbidimetry. CRP was detected by rate nephenometry. The detection results were used for analyzing the clinical diagnostic value of ACLF with infection. Results(1)The level of PCT,DD and CRP in ACLF group were significantly higher than non-ACLF group and healthy controls(P<0.05).The levels of PCT,DD and CRP in the infection group were significantly higher than non-infection group(P<0.05).(2)The positive rates of PCT,DD and CRP in the infection group were 93.24%, 78.38%,89.19%,which were significantly higher than the non-infection group and healthy controls respectively (P < 0.05).(3)The sensitivity(93.24%)and specificity(90.00%)of PCT were the highest among all indexes. (4)The area under the ROC curve of PCT,DD,CRP were 0.892,0.715,0.755,respectively.PCT had the highest diagnostic value. Conclusion The levels of serum PCT,DD and CRP have a significant clinical value for the early diagnosis of ACLF with infection.
5.Design and application of ophthalmologic peri-operative information systems
Jun LIU ; Jinping HU ; Zheng LIU ; Ying CHE ; Sifan YU
Chinese Journal of Practical Nursing 2015;(30):2293-2297
Objective To research patients with ophthalmologic perioperative information systems, strengthening the information management of nursing work, achieving consensus and sharing of health care information resources, and then to explore the clinical application effects of this ophthalmologic peri- opera-tive information systems. Methods The convenient sampling method was used in the study. The control group was consisted of 1 740 patients in our hospital from January to March 2013 (before the application of ophthalmologic perioperative information systems). The observation group included 2 078 patients of the same hospital (after the application of ophthalmologic perioperative information systems). The control group adopted routine pre- operative information acquisition method, the observation group applied ophthalmologic perioperative information systems, which included input function, reading function and statistical function. The incidence rate of canceled operation and satisfaction were compared between two groups. Results Ophthalmologic peri- operative information systems provided patients with information gathering, query and analysis in different periods. The rate of the canceled operation reduced in the observation group from 3.74% (65/1 740) to 2.69% (56/2 078) in the control group, χ2=3.91, P<0.05. The satisfaction degree increased from 91.84 % (1 598/1 740) in the observation group to 96.78% (2 011/2 078) in the control group, χ2=44.60, P<0.05, the difference was statistically different. The hospitalization days from April to September in 2013 shortened compared with those of the same period in 2012. Conclusions Ophthalmologic peri- operative information systems promotes the scientific and informatization of nursing information, which is worthy of wide clinic application.

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