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.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.
3.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
4.The correlation between the increase of peripheral blood B cells and the recurrence of autoimmune encephalitis
Li LI ; Mange LIU ; Fei WANG ; Siyuan FAN ; Lin BAI ; Haitao REN ; Hongzhi GUAN
Chinese Journal of Neurology 2024;57(1):24-30
Objective:To analyze the correlation between peripheral blood lymphocyte subsets, especially B cells, and the relapse of autoimmune encephalitis (AE).Methods:A retrospective analysis was conducted on patients with AE who were diagnosed and treated in Peking Union Medical College Hospital from January 2012 to January 2023. The clinical data including gender, age and changes in related indicators of CD19 +B cells, CD16/56 +NK cells, CD3 +T cells, CD4 +T cells, CD8 +T cells, IgG, IgA, and IgM before and after recurrence were analyzed.Binary Logistic regression analysis was applied to the study of correlation between AE recurrence and gender, age, CD19 +B cells, CD16/56 +NK cells, CD3 +T cells, CD4 +T cells, CD8 +T cells, IgG, IgA and IgM. The receiver operating characteristic (ROC) curves of the cells that affect AE recurrence (CD19 +B cells, CD16/56 +NK cells, CD3 +T cells, CD4 +T cells and CD8 +T cells) were plotted separately. Results:A total of 198 eligible AE patients were included, including 98 males and 100 females, aged (39.52±17.91) years. Among these patients, 78 cases had relapses, with a recurrence rate of 39.4%. The results of Logistic regression analysis showed that CD19 +B cells ( B=0.006, P<0.001), CD16/56 +NK cells ( B=0.004, P<0.05), CD3 +T cells ( B=-0.011, P<0.05), CD4 +T cells ( B=0.014, P<0.05) and CD8 +T cells ( B=0.010, P<0.05) were highly correlated with the relapse of AE. ROC curve analysis showed that CD19 +B cells (area under the curve: 0.833, P<0.001, critical value: 73.5/μl; sensitivity: 69.2%, specificity: 86.7%), CD3 +T cells (area under the curve: 0.784, P<0.001), CD4 +T cells (area under the curve: 0.808, P<0.001), and CD8 +T cells (area under the curve: 0.742, P<0.001) all had a certain predictive value for AE relapse. Among all the indicators, the area under the curve of CD19 +B cells was the largest, which had a higher value in predicting AE recurrence. Conclusion:The increase in peripheral blood CD19 +B cells has high predictive value for the relapse of AE.
5.Current status of blood pressure control in elderly hypertensive patients under the antihypertensive standard recommended by Chinese experts
Qiongyi HE ; Xingman FAN ; Chenyue MA ; Meng WANG ; Jing ZHANG ; Haitao ZHANG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(1):34-37
Objective To analyze the antihypertensive compliance rate,drug use and complication distribution among very old hypertensive inpatients under the antihypertensive standard of 150/90 mm Hg in our country(1 mm Hg=0.133 kPa).Methods A total of 409 hospitalized patients aged ≥80 years and diagnosed with hypertension in all departments of Air Force Medical Center of PLA were enrolled,and according to their clinical outcomes,they were divided into intensive antihypertensive group(106 cases,SBP<130 mm Hg),standard antihypertensive group(155 ca-ses,SBP 130-149 mm Hg)and non-standard blood pressure group(148 cases,SBP ≥150 mm Hg).The status of blood pressure control was analyze in each group.Results When 150/90 mm Hg was used as the blood pressure standard,25.9%were in the intensive blood pressure group,37.9%were in the standard blood pressure group,36.2%were in the non-standard blood pressure group.The proportion of patients aged>90 years was significantly lower in the non-standard blood pressure group than the intensive antihypertensive group and the standard anti-hypertensive group(4.1%vs 7.5%and 12.3%,P<0.05).The ratio of single-drug therapy was significantly higher in the standard antihypertensive group than the intensive antihypertensive group(46.5%vs 32.1%,P<0.05),and that of dual combination therapy was obviously higher in the intensive antihypertensive group than the standard antihypertensive group(35.8%vs 22.6%,P<0.05).The proportions of heart damage and cerebrovascular damage were significantly higher(43.4%vs 21.9%,26.4%vs 14.8%),and the proportion of complicated retinopathy was notably lower(11.3%vs 23.9%)in the intensive antihypertensive group than the standard antihypertens-ive group(P<0.05).Conclusion For very old hypertensive patients in our country,it is more sci-entific and practical to use 150/90 mm Hg as the starting standard for blood pressure reduction.Intensified blood pressure reduction increases cardiovascular and cerebrovascular damages in them instead.
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.Different methods for treating pulmonary arteriovenous malformation under multi-disciplinary treatment model
Zeyang FAN ; Peng HUANG ; Haitao GUAN ; Yinghua ZOU
Chinese Journal of Interventional Imaging and Therapy 2024;21(1):12-16
Objective To observe the effectiveness and safety of different methods under multi-disciplinary treatment(MDT)model for treating pulmonary arteriovenous malformation(PAVM).Methods MDT were retrospectively performed in 31 patients with PAVM.The effectiveness and safety of interventional therapy,surgical treatment and conservative therapy for PAVM were compared.Results Among 31 cases of PAVM,22 cases underwent interventional therapies(interventional group),4 cases received surgical treatments(surgical group)and 5 cases underwent conservative therapies(conservative group).In interventional group,PAVM was successfully embolized in all 22 cases,with the technical success rate was 100%(22/22).Pleurisy was occurred in 3 cases(3/22,13.64%),while recurrence of PAVM was noticed in 4 cases(4/22,18.18%)during follow-up.No recurrence occurred in interventional group after the second interventional therapies.In surgical group,4 cases were successfully treated with thoracoscopic lobectomy,with the technical success rate of 100%(4/4).No postoperative complication occurred,while recurrence of PAVM was noticed in 2 cases(2/4,50.00%)during follow-up,including 1 case underwent interventional therapy and 1 case underwent conservative therapy.In conservative group,progressive PAVM was observed in 3 cases(3/5,60.00%),including 2 cases who were cured with interventional therapy and 1 case died of stroke after conservative therapy.Conclusion Individualized treatments of PAVM were feasible under MDT model.Compared with surgical treatments and conservative therapies,interventional therapies of PAVM were more effective and relatively safe.
8.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.
9.HDCGUnet:a neural network for image segmentation of calcium imaging
Wenlong XIA ; Yan WU ; Zhe ZHAO ; Ming FAN ; Haitao WU
Military Medical Sciences 2024;48(2):122-128
Objective To build a neural network based on the Unet infrastructure for recognition and segmentation of two-dimensional calcium imaging fluorescence images.Methods The in vivo miniaturized two-photon microscope(mTPM)was used for brain calcium imaging in freely moving mice.The imaging data was motion corrected using the NoRMCorre algorithm and processed using ImageJ software to obtain the original images after correction,and the labels were produced using the Labelme software.The neural network HDCGUnet was built using the original images and labels for training,and optimized to improve the model structure according to the training effect.Finally,the evaluation indexes were selected and compared with those of other models to verify the utility of this model.Results The HDCGUnet model,which was collected and made on our own,performed best in the two-photon calcium imaging dataset compared to other models,and performed well on the BBBC dataset either.Conclusion The HDCGUnet model provides a novel alternative for the recognition and segmentation of two-photon calcium imaging images.
10.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.

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