1.Advancements in the research of the structure, function, and disease-related roles of ARMC5.
Yang QU ; Fan YANG ; Yafang DENG ; Haitao LI ; Yidong ZHOU ; Xuebin ZHANG
Frontiers of Medicine 2025;19(2):185-199
The armadillo repeat containing 5 (ARMC5) gene is part of a family of protein-coding genes that are rich in armadillo repeat sequences, are ubiquitously present in eukaryotes, and mediate interactions between proteins, playing roles in various cellular processes. Current research has demonstrated that reduced expression or absence of the ARMC5 gene in various tumor tissues can lead to uncontrolled cell proliferation, thereby inducing a range of diseases. The ARMC5 gene was initially extensively studied in the context of bilateral macronodular adrenocortical disease (BMAD), with harmful pathogenic variants in ARMC5 identified in approximately 50% of BMAD patients. With advancing research, scientists have discovered that ARMC5 pathogenic variants may also have potential effects on other diseases and could be associated with increased susceptibility to certain cancers. This review aims to present the latest research progress on how the ARMC5 gene plays its role in tumors. It outlines the basic structure of ARMC5 and the regions where it functions, as well as the diseases currently proven to be associated with ARMC5. Moreover, some evidence suggests its relation to embryonic development and the regulation of immune system activity. In conclusion, the ARMC5 gene is a crucial focal point in genetic and medical research. Understanding its function and regulation is of great importance for the development of new therapeutic strategies related to diseases associated with its pathogenic variants.
Humans
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Neoplasms/genetics*
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Armadillo Domain Proteins/genetics*
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Animals
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Genetic Predisposition to Disease
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Cytoskeletal Proteins/genetics*
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Tumor Suppressor Proteins/genetics*
2.Investigation and analysis of external exposure levels of radiation workers in selected veterinary clinics in China, 2022
Shuxia HAO ; Haitao YU ; Mengxue LI ; Shengnan FAN ; Tuo WANG ; Jingguo ZHANG ; Jun DENG
Chinese Journal of Radiological Health 2024;33(6):649-653
Objective With the increase in pet-owning households in China, veterinary clinics have increased at an annual rate of 19.86%. However, the management blind area that may exist in multi-department supervision has led to a significantly worse working environment of radiation workers in veterinary clinics than that of medical institutions. The purpose of this study was to understand the levels of occupational external exposure of radiation workers in veterinary clinics in China, analyze the occupational risks faced by radiation workers in veterinary clinics, contribute to the protection of the occupational health of radiation workers, and provide data and scientific basis for the formulation of national relevant regulations and standards. Methods The individual dose monitoring data of radiation workers in selected veterinary clinics in 2022 were obtained from the National Individual Dose Registration System. Results This study involved 1868 radiation workers from
3.High LINC00626 expression promotes esophagogastric junction adenocarcinoma metastasis:the mediating role of the JAK1/STAT3/KHSRP axis
Feng ZHANG ; Linlin FAN ; Xia KANG ; Haitao WEI ; Li LI
Journal of Southern Medical University 2024;44(3):541-552
Objective To investigate the role of JAK1/STAT3/KHSRP axis in mediating the regulatory effect of LINC00626 on progression of esophagogastric junction adenocarcinoma.Methods We collected surgical tumor and adjacent tissue specimens from 64 patients with esophagogastric junction adenocarcinoma and examined the expression levels of LINC00626 and KHSRP.qRT-PCR was used to detect the expressions of LINC00626 and KHSRP in 6 esophageal adenocarcinoma cell lines(OE-19,TE-7,Bic-1,Flo-1,SK-GT-4,and BE-3)and a normal esophageal epithelial cell line(HET-1A).OE-19 and TE-7 cell lines with stable LINC00626 knockdown and FLO-1 and SK-GT-4 cells stably overexpressing LINC00626 were constructed by lentiviral transfection,and the changes in proliferation,migration and invasion of the cells were evaluated using Cell Counting Kit-8(CCK-8)assay and Transwell migration/invasion assay.The expressions of KHSRP and JAK/STAT pathway proteins in the transfected cells were detected with Western blotting.The effects of LINC006266 knockdown and overexpression on subcutaneous tumor formation and lung metastasis of OE-19 and FLO-1 cell xenografts were tested in nude mice.Results The expression levels of LINC00626 and KHSRP were significantly increased in esophagogastric junction adenocarcinoma tissues and in esophageal adenocarcinoma cells.LINC00626 knockdown obviously inhibited the proliferation,migration and invasion of esophageal adenocarcinoma cells in vitro and decreased their tumor formation and lung metastasis abilities in nude mice,while overexpression of LINC00626 produced the opposite effects.In esophageal adenocarcinoma cells,LINC0626 knockdown significantly decreased and LINC00626 overexpression strongly enhanced the phosphorylation of JAK1 and STAT3.Conclusion High LINC00626 expression promotes esophageal-gastric junction adenocarcinoma metastasis by activating the JAK1/STAT3/KHSRP signal axis.
4.The value of quantitative flow ratio in the hemodynamic evaluation of myocardial bridge
Meng WANG ; Xingman FAN ; Quanlong WANG ; Yukun CAO ; Chenyue MA ; Qiongyi HE ; Haitao ZHANG
Chinese Journal of Cardiology 2024;52(2):165-171
Objective:To explore the application value of quantitative flow ratio (QFR) in the hemodynamic evaluation of myocardial bridge and to preliminarily evaluate the correlation and related influencing factors between deformation quantitative flow ratio (D-QFR) and QFR.Methods:This is a cross-sectional study. Patients with CAG-confirmed simple myocardial bridge of the middle anterior descending coronary artery from June 2012 to June 2022 at the Air Force Medical Center were retrospectively included in this study. Systolic stenosis of mural coronary arteries (MCA) and myocardial bridge length were measured using quantitative coronary angiography. The patients were divided into mild stenosis group (<50% systolic stenosis) and moderate-to-severe stenosis group (≥50% systolic stenosis) according to the Nobel grading criteria. At different time periods (systolic and diastolic), the QFR values were measured at 3 locations (1 to 2 cm before the MCA entrance, the middle segment of the MCA, and 1 to 2 cm after the MCA exit), denoted as QFRa, QFRb, and QFRc, respectively, and the D-QFR values, incorporating vessel deformation information, were recorded. The MCA distal QFR≤0.8 in either stage was defined as an abnormal QFR value. QFR values were compared between the two groups at different locations and within each group. Factors associated with abnormal QFR values were analysed using multifactorial logistic regression. Spearman rank correlation analysis was used to examine the correlation between D-QFR values and systolic and diastolic QFR values.Multiple linear regression was used to analyse the factors associated with D-QFR.Results:A total of 83 patients were enrolled, including 58 males, aged (57.1±13.1) years. There were 48 cases in the mild stenosis group and 35 cases in the moderate-to-severe stenosis group, and the differences in systolic and diastolic QFRb and QFRc values between the two groups were statistically significant (all P<0.05). Within-group comparisons showed the values of QFRb and QFRc in the systolic phase were lower than those in the diastolic phase; QFRb and QFRc were both lower than QFRa during the same period (all P<0.05). Multifactorial logistic regression analysis showed that MCA systolic stenosis ( OR=1.225, 95% CI 1.093-1.372, P<0.001) was an influential factor for abnormal QFR. D-QFR values were positively correlated with both systolic and diastolic QFR values (correlation coefficients were 0.849 and 0.675, respectively, both P<0.01). Multiple linear regression analysis showed that D-QFR values were negatively correlated with age ( β=-0.208, P=0.029), systolic stenosis ( β=-0.500, P<0.001), and myocardial bridge length ( β=-0.211, P=0.036). Conclusions:The QFR values in middle and distal of myocardial bridge decrease. The systolic stenosis rate of myocardial bridge is an important factor affecting QFR value. D-QFR is positively correlated with both systolic and diastolic QFR values. Age, myocardial bridge systolic stenosis rate and length are factors influencing the D-QFR values.
5.High LINC00626 expression promotes esophagogastric junction adenocarcinoma metastasis:the mediating role of the JAK1/STAT3/KHSRP axis
Feng ZHANG ; Linlin FAN ; Xia KANG ; Haitao WEI ; Li LI
Journal of Southern Medical University 2024;44(3):541-552
Objective To investigate the role of JAK1/STAT3/KHSRP axis in mediating the regulatory effect of LINC00626 on progression of esophagogastric junction adenocarcinoma.Methods We collected surgical tumor and adjacent tissue specimens from 64 patients with esophagogastric junction adenocarcinoma and examined the expression levels of LINC00626 and KHSRP.qRT-PCR was used to detect the expressions of LINC00626 and KHSRP in 6 esophageal adenocarcinoma cell lines(OE-19,TE-7,Bic-1,Flo-1,SK-GT-4,and BE-3)and a normal esophageal epithelial cell line(HET-1A).OE-19 and TE-7 cell lines with stable LINC00626 knockdown and FLO-1 and SK-GT-4 cells stably overexpressing LINC00626 were constructed by lentiviral transfection,and the changes in proliferation,migration and invasion of the cells were evaluated using Cell Counting Kit-8(CCK-8)assay and Transwell migration/invasion assay.The expressions of KHSRP and JAK/STAT pathway proteins in the transfected cells were detected with Western blotting.The effects of LINC006266 knockdown and overexpression on subcutaneous tumor formation and lung metastasis of OE-19 and FLO-1 cell xenografts were tested in nude mice.Results The expression levels of LINC00626 and KHSRP were significantly increased in esophagogastric junction adenocarcinoma tissues and in esophageal adenocarcinoma cells.LINC00626 knockdown obviously inhibited the proliferation,migration and invasion of esophageal adenocarcinoma cells in vitro and decreased their tumor formation and lung metastasis abilities in nude mice,while overexpression of LINC00626 produced the opposite effects.In esophageal adenocarcinoma cells,LINC0626 knockdown significantly decreased and LINC00626 overexpression strongly enhanced the phosphorylation of JAK1 and STAT3.Conclusion High LINC00626 expression promotes esophageal-gastric junction adenocarcinoma metastasis by activating the JAK1/STAT3/KHSRP signal axis.
6.LINC00626 promotes the malignant process of colorectal cancer metastasis through the JAK1/STAT3/KHSRP axis
Yanyan YU ; Xia KANG ; Linlin FAN ; Haifeng ZHANG ; Xiaolong WANG ; Haitao WEI ; Li LI
The Journal of Practical Medicine 2024;40(12):1643-1650
Objective To examine the regulation of malignant progression of colorectal cancer by LINC00626 via the JAK1/STAT3/KHSRP signaling axis and its molecular mechanism.Methods 96 individuals diagnosed with colorectal cancer at our hospital during June 11,2021 and June 11,2023 were chosen as research subjects,and their cancerous tissue and nearby normal tissue were collected.Cultivate colorectal cancer cell lines(SW620,HCT116,HT29,DLD-1,LOVO,Caco-2)and normal colorectal cells(NCM460)in vitro,and detect the expression of LINC00626 and KHSRP in colorectal cancer tissue and cell lines using qRT-PCR.Screening out cell lines infected with lentivirus,SW620 and HCT116 cell lines were transfected with knockdown lentivirus and its control,while HT29 and DLD-1 cell lines were transfected with overexpressing lentivirus and its control,respectively.Select stable transfected cell lines for cell function experiments to detect proliferation,migration,and invasion abilities.Detection of the effect of LINC00626 on the growth and migration of colorectal cancer tumors in live mouse experiments.The expression level of KHSRP protein in stable labeled cells was determined using a western blot analysis.Rescue experimental research on the regulatory relationship between LINC00626 and KHSRP.Results qRT-PCR showed low expression of LINC00626 and high expression of KHSRP in colorectal cancer tissues and cell lines.Cell function experiments showed that compared with the sh-NC group,the sh-LINC00626 group promoted cell proliferation,migration,and invasion in SW620 and HCT116 cells,while the overexpression group showed the opposite.Cell rescue experiments showed that,LINC00626+KHSRP significantly reversed the promotion effects of knocking down LINC00626 on cell proliferation,migration,and invasion.In the nude mouse experiment,com-pared with the sh-NC group,the sh-LINC00626 group showed a significant increase in tumor volume and weight,cell proliferation rate,and the number of lung metastases from colorectal cancer in the nude mice;Overexpression results in the opposite.The signal pathway experiment revealed that relative to the sh-NC group,the expression levels of JAK1 and STAT3 mRNA in the sh-LINC00626 group were significantly increased,whereas the results in the overexpression group were the opposite.Conclusion LINC00626 suppression the malignant progression of colorec-tal cancer metastasis through the JAK1/STAT3/KHSRP signaling axis.
7.Impact of Physician Cumulative Workload on the Diagnostic Results of the Head-up Tilt Test for Vasovagal Syncope
Xiaosheng CHEN ; Jia HE ; Yandong SU ; Haitao YANG ; Xiaohan FAN
Chinese Circulation Journal 2024;39(11):1103-1109
Objectives:The purpose of this study is to evaluate the impact of the cumulative workload of HUTT testing physicians on diagnostic outcomes. Methods:This study retrospectively and consecutively included the data of testing physicians and patients who underwent HUTT at Fuwai Hospital,Chinese Academy of Medical Sciences,from January 2016 to December 2022.Based on the cumulative workload of physicians during the period from the initiation of tilt tests at the hospital to the end of the study,the physicians were categorized into low (50-100 sases),moderate (100-350 sases),and high (1000-4000 sases) cumulative workload groups,the cumulatie workload of no physician is 351-999 sases.Additionally,physicians were grouped by sex,educational background,and professional title to analyze differences in diagnostic rates of tilt table test reports within and between these groups. Results:The study included 22 testing physicians and 6122 patients.There were statistically significant differences in the rates of positive,suspicious positive,and negative reports among the 22 physicians (P<0.001).The average suspicious positive report rate in the moderate cumulative workload group was significantly higher than in the low and high cumulative workload groups (3.21% vs.1.09% vs.1.62%,P=0.001).The suspicious positive report rate was higher in the female physician group compared to the male physician group (2.25% vs.1.07%,P=0.017),in the undergraduate physician group compared to the postgraduate physician group (2.46% vs.1.52%,P=0.013),and in the junior title group compared to the intermediate and senior title groups (3.40% vs.1.75% vs.2.53%,P=0.024).Multivariate logistic regression analysis showed that a moderate cumulative workload was an influencing factor for suspicious positive reports,regardless of whether negative or positive was used as the reference (all P<0.05). Conclusions:There are certain differences in the diagnostic report rates of HUTT among different individual physicians.Physicians with a moderate cumulative workload are more likely to issue suspicious positive HUTT diagnostic reports.
8.Efficacy and safety of hyperthermic intraperitoneal chemotherapy combined with immune checkpoint inhibitors in treatment of gastric cancer with ascites
Haitao LI ; Tongfei WANG ; Shuangyan ZHANG ; Hong XU ; Tian XU ; Fan YANG ; Lei WU ; Haoran ZHENG ; Biaofei YE
Cancer Research and Clinic 2024;36(11):852-857
Objective:To investigate the efficacy and safety of hyperthermic intraperitoneal chemotherapy combined with immune checkpoint inhibitors in treatment of gastric cancer with ascites.Methods:A retrospective case-control study was conducted. The clinical data of 39 gastric cancer patients with malignant ascites treated in Xi'an Third Hospital from May 2021 to June 2023 were retrospectively analyzed. All patients were divided into the routine group (18 cases) and the observation group (21 cases) according to different treatment methods. The patients in the routine group were treated with hyperthermic intraperitoneal chemotherapy combined with systemic intravenous chemotherapy; the patients in the observation group were treated with immune checkpoint inhibitors on the basis of hyperthermic intraperitoneal chemotherapy combined with systemic intravenous chemotherapy. The clinical efficacy, tumor marker levels, Karnofsky scores, and incidence of adverse reactions of both groups were compared. Kaplan-Meier method was used to analyze the overall survival (OS) of both groups.Results:There were 12 males (66.7%) and 6 females (33.3%) in the routine group, with the age of (57±13) years; 13 males (61.9%) and 8 females (38.1%) in the observation group, with the age of (59±12) years. After treatment, the serum carcinoembryonic antigen (CEA), carbohydrate 125 (CA125), carbohydrate 199 (CA199) levels in the 2 groups were lower than those before treatment, and the differences were statistically significant (all P < 0.05). After treatment, the serum CEA, CA125, CA199 levels in the observation group were lower than those in the routine group, and the differences were statistically significant (all P < 0.05). After treatment, Karnofsky scores in the observation group were higher than those before treatment [(78.6±7.5) scores vs. (69.5±8.9) scores], and Karnofsky scores in the observation group were higher than those in the routine group [(78.6±7.5) scores vs. (72.8±7.9) scores],and the differences were statistically significant ( t = -3.65, 2.33, all P < 0.05). The objective remission rate (ORR) was 55.6% (10/18) and 71.4%(15/21), respectively in the routine group and the observation group, and the difference was statistically significant ( χ2 = 9.24, P = 0.002). The median OS time was 38.97 months (95% CI: 34.99-42.95 months) and 23.62 months (95% CI: 18.49-28.74 months), respectively in the observation group and the routine group, and the difference was statistically significant ( χ2 = 3.88, P = 0.049). There was no statistically significant difference in the incidence of adverse events between the 2 groups (all P > 0.05). No serious treatment-related complications were found in the observation group. Conclusions:Hyperthermic intraperitoneal chemotherapy combined with immune checkpoint inhibitors shows a good therapeutic effect in the treatment of gastric cancer with ascites, and the adverse reactions are controllable.
9.A novel TNKS/USP25 inhibitor blocks the Wnt pathway to overcome multi-drug resistance in TNKS-overexpressing colorectal cancer.
Hongrui ZHU ; Yamin GAO ; Liyun LIU ; Mengyu TAO ; Xiao LIN ; Yijia CHENG ; Yaoyao SHEN ; Haitao XUE ; Li GUAN ; Huimin ZHAO ; Li LIU ; Shuping WANG ; Fan YANG ; Yongjun ZHOU ; Hongze LIAO ; Fan SUN ; Houwen LIN
Acta Pharmaceutica Sinica B 2024;14(1):207-222
Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APCmin/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.
10.Research progress in data processing methods of neuronal soma calcium imaging
Wenlong XIA ; Zhe ZHAO ; Ming FAN ; Haitao WU
Military Medical Sciences 2024;48(1):68-74
The recording and analysis of activities of calcium signals in neurons is of critical importance in the field of neuroscience.Over the past three decades,various fluorescent calcium imaging techniques not only have been used in the imaging study of functional activities of neuronal communities,but also can be combined with specific markers to record the functional activities of specific types of neuronal communities.To analyze neural activities at the cellular level,a series of preprocessing such as motion correction,cell body recognition,calcium signal extraction and peak deconvolution is required for the collected video.However,current methods for manual preprocessing are time-consuming and laborious,so computer automatic analysis technology is urgently needed to quickly repair the jitter in the video,identify the position and outline of a single cell,extract its activity trajectory and infer the action potential peak.In this paper,the methods of calcium imaging data processing used in recent years are summarized,and the future developments are predicted.

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