1.Role of mTOR signaling pathway in crizotinib-induced apoptosis of EML4-ALK fusion gene-positive lung adenocarcinoma cell line H2228
Hui DAI ; Xiangqun SONG ; Xingchen PAN ; Haiyan PENG ; Jiang WEI ; Shaozhang ZHOU
Chinese Journal of Pathophysiology 2014;(6):1103-1109
AIM:To investigate the mammalian target of rapamycin ( mTOR) signaling pathway as the center playing a role in the crizotinib-induced apoptosis of non-small cell lung cancer (NSCLC) cell line H2228, which represents positive echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene. METHODS:H2228 cells were processed according to different purposes .Fluorescence quantitative PCR is used to ob-serve the gene states .MTT assay is used to detect the cell inhibition rates .The cell apoptosis and cell cycle were analyzed by flow cytometry .The expression and activation levels of the key proteins in the mTOR signaling pathway were determined by Western blotting .RESULTS:Crizotinib promoted the apoptosis of H 2228 cells in a time-and dose-dependent manner . Crizotinib blocked the H2228 cells staying at the G1 phase.In apoptotic H2228 cells processed with crizotinib, the activa-tion level of mTOR was decreased , and the activation levels of the key proteins in upstream and downstream of mTOR path -way were both declined .The expression level of the fusion protein EML 4-ALK variant 3 was not affected , but its active form of p-ALK was significantly suppressed .CONCLUSION:mTOR signaling pathway has a certain relationship with the crizotinib-induced apoptosis of lung cancer cell H 2228, which represents positive EML4-ALK fusion gene.
2.Analysis of the monitoring results of nail snails in the Tongjiang River channel of Zhenjiang section on the south bank of Yangtze River from 2019 to 2023
WANG Zhiqin ; CHEN Xingchen ; SHEN Xuehui ; DAI Jianrong ; LI Aihua ; WANG Lin ; LI Yefang ; LI Zhiwei
China Tropical Medicine 2024;24(1):53-
Objective To timely understand the current status and distribution of nail snails (Oncomelania hupensis) in Tongjiang River channels in Zhenjiang City, providing a scientific basis for achieving the goal of eliminating schistosomiasis. Methods From 2019 to 2023, nine Tongjiang River channels on the south bank of the Yangtze River under the jurisdiction of Zhenjiang City were selected as the monitoring area. Snail monitoring was carried out onshore and beach nail snails floats in the Tongjiang River channels, nail snails on attachments in hardened areas, snails induced by straw curtains, and snails carried by boats and domestic animals. Results The monitoring results of shoreline snail from 2019 to 2023 showed that the snail situation in the Tongjiang River channel and its outer river bank remained relatively stable from 2019 to 2020; however, in 2021, under the influence of the Yangtze River flooding disaster in 2020, the area of snails increased significantly. In 2021, the area with snails in the Tongjiang River channel and the outer river bank increased by 45.70% (11.95/26.15) and 100.00% (20.00/20.00) compared to 2020; the average density of nails snails in the Tongjiang River channel and the outer river bank and the emergence rate of snail frames both showed a significant increase, rising by 94.73% (0.18/0.19) and 68.08% (8.68/12.75) compared to 2020, and by 122.73% (0.81/0.66) and 102.78% (43.26/42.09), respectively. The differences in the increase in the occurrence rate of spiked frames in the Tongjiang River channel Chili River and Renmin River were not statistically significant (χ2=0.329, P>0.05; χ2=0.646, P>0.05). From 2022 to 2023, the density of nail snails and the occurrence rate of framed snails in the Tongjiang River channel showed a decreasing trend (F=4.72, P=0.04 and χ2=372.58, P<0.01). The area of nail snails, density of live snails, and occurrence rate of framed snails in the outer river bank showed a decreasing trend (F=13.96, P=0.02; F=23.43, P<0.01; χ2=1 029.69, P<0.01). During the five years, no nail snails were detected in the ancient canal and 11 tributaries. From 2019 to 2023, 180 times of 3 003 kg of floating objects were salvaged, with a total of 148 live snails detected. A total of 17 live snails were captured on attachments in the hardened berm area; a total of 11 live snails were captured by straw curtain snail baiting;112 boats were inspected, and no snails were found; there were 112 boats surveyed, and no snails were found; 97 cattle were observed, and 2 cattle were found to carry 1 live snail on their hooves; 321 sheep were observed, and no snails were found on their hooves; and no infectious snails were found in the monitoring area in 5 years. Conclusions Nail snails continue to exist in the Tongjiang River channel, and the risk factors for schistosomiasis transmission have not been completely eliminated. It is still necessary to carry out accurate monitoring of the snail situation in the Tongjiang River and the river bank, so as to grasp the risk of transmission in time and take emergency measures.
3.Identification of an immune-related risk signature and nomogram predicting the overall survival in patients with endometrial cancer
Yuan CHENG ; Xingchen LI ; Yibo DAI ; Yangyang DONG ; Xiao YANG ; Jianliu WANG
Journal of Gynecologic Oncology 2021;32(3):e30-
Objective:
Aimed to construct an immune-related risk signature and nomogram predicting endometrial cancer (EC) prognosis.
Methods:
An immune-related risk signature in EC was constructed using the least absolute shrinkage and selection operator regression analysis based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A nomogram integrating the immune-related genes and the clinicopathological characteristics was established and validated using the Kaplan-Meier survival curve and receiver operating characteristic (ROC) curve to predict the overall survival (OS) of EC patients. The Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) R tool was used to explore the immune and stromal scores.
Results:
CCL17, CTLA4, GPI, HDGF, HFE2, ICOS, IFNG, IL21R, KAL1, NR3C1, S100A2, and S100A9 were used in developing an immune-related risk signature evaluation model. The Kaplan-Meier curve indicated that patients in the low-risk group had better OS (p<0.001).The area under the ROC curve (AUC) values of this model were 0.737, 0.764, and 0.782 for the 3-, 5-, and 7-year OS, respectively. A nomogram integrating the immune-related risk model and clinical features could accurately predict the OS (AUC=0.772, 0.786, and 0.817 at 3-, 5-, and 7-year OS, respectively). The 4 immune cell scores were lower in the high-risk group. Forkhead box P3 (FOXP3) and basic leucine zipper ATF-like transcription factor (BATF) showed a potential significant role in the immune-related risk signature.
Conclusion
Twelve immune-related genes signature and nomogram for assessing the OS of patients with EC had a good practical value.
4.Application of binomial distribution-based statistical process control method in blood quality control
Xingchen LIU ; Huayou DAI ; Junhong YANG ; Danli CUI ; Siqi WU ; Pengwei YIN ; Xia HUANG ; Yongzhu XU
Chinese Journal of Blood Transfusion 2024;37(2):196-202
【Objective】 This study endeavors to introduce the statistical process control (SPC) method to analyze the quality control index concerning red blood cells in additive solution with leukocytes reduced, with the aspiration to advance the effective utilization of blood quality control data, thereby providing empirical foundations for the continual enhancement of blood quality. 【Methods】 Between 2020 and 2022, test data pertaining to the quality control index of red blood cells in additive solution with leukocytes reduced were amassed from six blood stations in Chongqing area. Utilizing Minitab software, the SPC analysis was carried out, p-control charts were delineated, the non-conformance rates of each quality control index along with their 95% confidence intervals were computed, as well as the Process Capability Index (Z value). 【Results】 In accordance with the Whole Blood and Blood Components Quality Requirements, the appraisal of the quality control indexes for red blood cells in additive solution with leukocytes reduced manifested a conformity rate of 100% for appearance, end-of-storage hemolysis rate and sterility test. Nonetheless, the conformity rates for volume, hemoglobin, hematocrit and residual leukocytes did not attain 100%, albeit all were ≥75%. Through the employment of binomial distribution-based p-control charts, the controlled state of the production process was discerned. Although the overarching conformity rate satisfied the national standard stipulations, it was discerned that there were out-of-control points concerning volume, hemoglobin, hematocrit, and residual leukocytes across different institutions, exhibiting palpable trends. The non-conformance rates of all quality control indexes were less than 25%, yet at a 95% confidence level, the residual leukocyte counts from institutions B, C, E, and F did not adhere to the stipulations (exceeding 25%). By architecting the ability evaluation index Z value for count data process capability analysis, it was unveiled that the volume of institution E, the hematocrit of institutions B, C, and F, and the residual leukocytes Z values of all six blood collection and supply institutions were below 2, hinting at avenues for amelioration. 【Conclusion】 The SPC method anchored in binomial distribution exhibits substantial application merit in blood component quality management, facilitating real-time surveillance of blood collection, preparation, and storage procedures.
5.Expression and clinical significance of Hsp90α in colon adenocarcinoma
Yang ZHANG ; Xiaoting WU ; Fang WANG ; Xingchen DAI ; Yuhuan ZHANG ; Yujing GAO
Chinese Journal of Clinical and Experimental Pathology 2024;40(8):845-852
Purpose To investigate the expression and po-tential clinical value of heat shock protein 90α(Hsp90α)in co-lon adenocarcinoma.Methods The expression level of Hsp90αin colon adenocarcinoma and its relationship with clinicopatho-logical features,prognosis and immune cell infiltration were ana-lyzed by bioinformatics and immunohistochemistry.The prolifer-ation ability of colon cancer cells before and after Hsp90AA1 knockout was detected by CCK-8 cell proliferation assay and plate cloning assay.Results The bioinformatics tools showed that Hsp90AA1 was abnormally higher in colon cancer tissues than adjacent tissues,and the higher the expression level,the worse the prognosis of patients.The expression of Hsp90AA1 was positively correlated with the infiltration levels of CD4+T cells(Th2),CD8+T cells,myeloid inhibitory cells,Tregs cells,neutrophils,macrophages,M1 macrophages and M2 macropha-ges.Immunohistochemical results showed that the expression of Hsp90α in colon cancer tissues was significantly higher than in its adjacent tissues.The expression of Hsp90α was related to age(P<0.05),not related to gender,tumor size,location,clini-cal classification,differentiation degree,tumor node metastasis,lympho-vascular invasion,perineural invasion(P>0.05).The high expression of Hsp90α was an independent risk factor for the prognosis of colon cancer patients.The results of cell experi-ments showed that Hsp90AA1 knockout inhibited the growth and proliferation of colon cancer cells.Conclusion Hsp90α is highly expressed in colon adenocarcinoma,which may be a po-tential molecular marker for poor prognosis of colon adenocarci-noma.