1.Application of AI software for chromosomal aberration analysis in occupational health surveillance and radiation biological dose estimation
Yingyi PENG ; Qiuying LIU ; Zhifang LIU ; Zongjun ZHANG ; Xiaoyan CHEN ; Kunjie HUANG ; Qiying NONG ; Na ZHAO
China Occupational Medicine 2025;52(2):171-175
Objective To explore the feasibility of applying artificial intelligence (AI) technology in chromosomal aberration (CA) analysis for occupational health surveillance of radiation workers and in biological dose estimation during nuclear emergency responses. Methods Peripheral blood samples from healthy volunteers were irradiated in vitro with X-rays and cobalt-60 (⁶⁰Co) γ rays. Chromosome slides were prepared using an automated harvesting and dropping device. The data training and outcome evaluation of CA analysis was performed on the AI software using chromosome images from occupational medical examination of radiation workers from the current lab or chromosome slides from blood samples irradiated with X-rays. The trained AI software was then used to assist in CA analysis and biological dose estimation among occupational medical examination of radiation workers, with results compared with manual reading and actual exposure doses. Results The trained AI software achieved a CA recognition accuracy of 95.11%. In the occupational health examination of radiation workers, the positive CA detection rate using AI + manual review was 2.25% higher than that in manual reviewing alone. The errors in biological dose estimation for ⁶⁰Co γ rays and X-rays using AI + manual review analysis were 11.86% and 7.33%, respectively, both within the acceptable 20.00% error margin. Conclusion AI + manual review can be effectively applied in CA analysis for occupational health examination and biological dose estimation during nuclear emergencies, significantly improving analysis efficiency.
2.USP51/GRP78/ABCB1 axis confers chemoresistance through decreasing doxorubicin accumulation in triple-negative breast cancer cells.
Yang OU ; Kun ZHANG ; Qiuying SHUAI ; Chenyang WANG ; Huayu HU ; Lixia CAO ; Chunchun QI ; Min GUO ; Zhaoxian LI ; Jie SHI ; Yuxin LIU ; Siyu ZUO ; Xiao CHEN ; Yanjing WANG ; Mengdan FENG ; Hang WANG ; Peiqing SUN ; Yi SHI ; Guang YANG ; Shuang YANG
Acta Pharmaceutica Sinica B 2025;15(5):2593-2611
Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.
3.Biological dose estimation in a patient with radiation dermatitis
Zhifang LIU ; Yingyi PENG ; Xiaolian LIU ; Qiying NONG ; Qiuying LIU ; Na ZHAO ; Xiaoyong LIU ; Weixu HUANG
China Occupational Medicine 2025;52(4):410-415
Objective To estimate the biological dose in a patient who developed radiation dermatitis after a local X-ray exposure incident. Methods Peripheral blood samples, which were used to performed lymphocyte chromosome aberration analysis, were collected from the patient at 54 and 102 days after the last exposure. Biological dose in the patient was estimated using four published X-ray dose-effect calibration curves for chromosomal aberrations. The absorbed dose in the patient was reconstructed using Dolphin′s model and time correction factors. Results The abnormal rates of chromosome aberration at 54 and 102 days after exposure were 1.00% and 0.40%, respectively. Based on the four calibration curves, the estimated local exposure dose at 54 day ranged from 3.59 to 10.51 Gy, and the time-corrected whole-body equivalent dose ranged from 0.27 to 0.87 Gy. The local dose estimated at 102 days ranged from 2.24 to 6.64 Gy, with a time-corrected whole-body equivalent dose of 0.12 to 0.60 Gy, which differed from the day-54 estimates. The biological doses estimated by both methods were lower than the physical dose (29.43 Gy). Conclusion The estimation of local biological dose of patient various in four dose-effect curves selected in this study. Delayed blood sampling will lead to underestimate biological dose. Early blood collection after radiation incidents is critical to ensure accuracy and reliability. Moreover, biological dose reconstruction methods for complex exposure scenarios require further research to improve the accracy of emergency response in radiation accidents.
4.Study on survival analysis and influencing factors of pneumoconiosis patients in Guangzhou
Huiting LIU ; Boning ZHENG ; Qiuying MO ; Yang LIAO
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(11):825-830
Objective:To analyze the survival of pneumoconiosis patients in Guangzhou from 1958 to 2018, explore the factors affecting the survival of pneumoconiosis, and provide scientific basis for formulating the guidelines and policies for treatment and assistance of pneumoconiosis.Methods:From July 2019 to January 2020, 1194 cases of occupational pneumoconiosis patients diagnosed by institutions qualified for pneumoconiosis diagnosis in Guangzhou from June 1, 1958 to December 31, 2018 were studied. Excluding 258 patients who lacked survival data, 936 patients were included in the pneumoconiosis survival analysis. Life table method was used to estimate the survival rate, Kaplan-Meier method was used to draw the survival curve, log-rank test was used to compare the groups, and Cox proportional risk regression model was used to analyze the influencing factors of survival.Results:The 10, 20 and 30 years cumulative survival rates of pneumoconiosis patients in Guangzhou were 62.8%, 35.2% and 15.4%, respectively. The median survival time was 19.4 years. log-rank test showed that there were statistically significant differences in the survival curves of pneumoconiosis patients between group without tuberculosis and group with tuberculosis ( P<0.001), and there were statistically significant differences among different stages and categories of pneumoconiosis ( P<0.001). Age of exposure to dust ( HR=1.03, 95% CI: 1.01-1.05), age of diagnosis ( HR=1.02, 95% CI: 1.00-1.04), combined pulmonary tuberculosis ( HR=1.46, 95% CI: 1.18-1.81), stage of pneumoconiosis (stage Ⅲ vs. stage Ⅰ, HR=2.26, 95% CI: 1.47-3.48) and categories of pneumoconiosis (fibrogenic mineral dust pneumoconiosis and metallogenic pneumoconiosis, HR=2.45, 95% CI: 1.61-3.74; non-fibrogenic mineral pneumoconiosis and metallogenic pneumoconiosis, HR=2.67, 95% CI: 1.47-4.87; mixed pneumoconiosis and metallogenic pneumoconiosis, HR=2.25, 95% CI: 1.11-4.56) were the factors affecting the survival time of pneumoconiosis patients ( P<0.05) . Conclusion:Pulmonary tuberculosis may increase the risk of death in patients with pneumoconiosis. Mineral dust pneumoconiosis, mixed pneumoconiosis and stage Ⅲ pneumoconiosis may also have higher risk of death.
5.Endogenous metabolite nicotinamide alleviates spontaneous lupus nephritis progression in a mouse model
Yanyan SHEN ; Yanhong LIU ; Qiuying HAN ; Ailing LI ; Qing XIA ; Xuemin ZHANG ; Weina ZHANG
Military Medical Sciences 2024;48(6):468-473
Objective To construct an NZB/W(F1)mouse model of systemic lupus erythematosus and evaluate the effects of nicotinamide on each index of lupus nephritis pathogenesis of NZB/W(F1)mice in order to provide data for research on the role of nicotinamide in the treatment of lupus nephritis.Methods Female NZB/W(F1)mice were obtained by crossing male NZW mice with female NZB ones.Urine samples were collected using metabolic cages and proteinuria test strips were used to detect proteinuria.Blood samples were collected through the orbital venous plexus in mice.Enzyme-linked immunosorbent assay(ELISA)was used to detect the level of anti-dsDNA antibody.Levels of serum creatinine and urea nitrogen and liver function indexes were detected using an automatic blood analyzer.Hematoxylin-eosin staining and immunofluorescence technique were used to detect the pathological state of the kidney.Results The levels of proteinuria,double-stranded DNA antibodies,serum creatinine,and urea nitrogen were gradually increased during the natural course of the disease in female NZB/W(F1)mice,indicating that the lupus nephritis disease model was constructed in female NZB/W(F1)mice.Compared to the control group,nicotinamide feeding could obviously decrease the level of proteinuria(P=0.0070),inhibit the production of double-stranded DNA antibodies(P=0.0325),and retard the progression of serum creatinine(P=0.0067)and urea nitrogen indexes(P=0.0166)in serum.In addition,the pathological state of the kidney in the nicotinamide feeding group was significantly alleviated compared with the control group.Conclusion A lupus nephritis disease model is constructed in NZB/W(F1)mice.Nicotinamide feeding can obviously alleviate the disease state of lupus nephritis in NZB/W(F1)mice.
6.Combined application of auditory brainstem response and auditory steady-state response in the evaluation of infants with mild sensorineural hearing loss
Qiuya JIANG ; Qiuying XIE ; Yu HUANG ; Chao HUANG ; Hongli LAN ; Maojie LIU ; Dan LAI
The Journal of Practical Medicine 2024;40(16):2305-2310
Objective To investigate the significance of auditory brainstem response(ABR)combined with auditory steady-state response(ASSR)for the assessment of mild sensorineural hearing loss in infants.Methods Data from 114 infants with mild sensorineural hearing loss were retrospectively analyzed,and their ABR and ASSR results were collected for rank sum test and correlation analysis.Results In the rank sum test,the difference in thresholds between tone-burst ABR(Tb-ABR)and ASSR at 0.5,1,2,4 kHz was statistically significant(P<0.05),and they were also correlated at 0.5,1,2,4 kHz(P<0.05),r=0.613,0.569,0.616,0.71.After grouping by gender and ear,there was a correlation between ABR and ASSR at 0.5,1,2,and 4 kHz,male:r=0.61,0.56,0.671,0.774;female:r=0.581,0.558,0.546,0.608;left ear:r=0.61,0.558,0.576,0.715;right ear:r=0.631,0.581,0.662,0.71.And after grouping by age at diagnosis,only infants diagnosed from 7~12 months of age did not correlate at 0.5 kHz and 1 kHz(P>0.05),while the rest of the groups had a good correlation(P<0.05),0~3 months:r=0.686,0.643,0.671,0.742;4~6 months:r=0.671,0.626,0.616,0.693;7~12 months at 2 kHz and 4 kHz:r=0.571,0.706.Conclusion In infants with mild sensorineural hearing loss,ABR and ASSR correlate in assessing hearing thresholds at all frequencies,and the combination of the two tests could provide a more accurate assessment of the subject's true hearing.
7.Comparison of interobserver variations in delineation of target volumes and organs-at-risk for intensity-modulated radiotherapy of nasopharyngeal carcinoma among physicians from different levels of cancer centers
Meining CHEN ; Yimei LIU ; Yinglin PENG ; Qiuying XIE ; Jinping SHI ; Rong HUANG ; Chong ZHAO ; Xiaowu DENG ; Meijuan ZHOU
Chinese Journal of Medical Physics 2024;41(3):265-272
Objective To assess inter-observer variations(IOV)in the delineation of target volumes and organs-at-risk(OAR)for intensity-modulated radiotherapy(IMRT)of nasopharyngeal carcinoma(NPC)among physicians from different levels of cancer centers,thereby providing a reference for quality control in multi-center clinical trials.Methods Twelve patients with NPC of different TMN stages were randomly selected.Three physicians from the same municipal cancer center manually delineated the target volume(GTVnx)and OAR for each patient.The manually modified and confirmed target volume(GTVnx)and OAR delineation structures by radiotherapy experts from the regional cancer center were used as the standard delineation.The absolute volume difference ratio(△V_diff),maximum/minimum volume ratio(MMR),coefficient of variation(CV),and Dice similarity coefficient(DSC)were used to compare the differences in organ delineation among physicians from different levels of cancer centers and among the 3 physicians from the same municipal cancer center.Furthermore,the IOV of GTVnx and OAR among physicians from different levels cancer centers were compared across different TMN stages.Results Significant differences in the delineation of GTVnx were observed among physicians from different levels of cancer centers.Among the 3 physicians,the maximum values of △V_diff,MMR,and CV were 97.23%±83.45%,2.19±0.75,and 0.31±0.14,respectively,with an average DSC of less than 0.7.Additionally,there were considerable differences in the delineation of small-volume OAR such as the left and right optic nerves,chiasm,and pituitary,with average MMR>2.8,CV>0.37,and DSC<0.51.However,relatively smaller differences were observed in the delineation of large-volume OAR such as the brainstem,spinal cord,left and right eyeballs,and left and right mandible,with average△V_diff<42%,MMR<1.55,and DSC>0.7.Compared with the differences among physicians from different levels cancer centers,the differences among the 3 physicians from the municipal cancer center were slightly reduced.Furthermore,there were also differences in the delineation of target volumes for NPC among physicians from different levels cancer centers,depending on the staging of the disease.Compared with the delineation of target volumes for earlier stage patients(stages I or II),the differences among physicians in the delineation of target volumes for advanced stage patients(stages III or IV)were smaller,with average △V_diff and DSC of 98.31%±67.36%vs 69.38%±72.61%(P<0.05)and 0.55±0.08 vs 0.72±0.12(P<0.05),respectively.Conclusion There are differences in the delineation of GTVnx and OAR in radiation therapy for NPC among physicians from different levels of cancer centers,especially in the delineation of target volume(GTVnx)and small-volume OAR for early-stage patients.To ensure the accuracy of multicenter clinical trials,it is recommended to provide unified training to physicians from different levels of cancer centers and review their delineation results to reduce the effect of differences on treatment outcomes.
8.Study on survival analysis and influencing factors of pneumoconiosis patients in Guangzhou
Huiting LIU ; Boning ZHENG ; Qiuying MO ; Yang LIAO
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(11):825-830
Objective:To analyze the survival of pneumoconiosis patients in Guangzhou from 1958 to 2018, explore the factors affecting the survival of pneumoconiosis, and provide scientific basis for formulating the guidelines and policies for treatment and assistance of pneumoconiosis.Methods:From July 2019 to January 2020, 1194 cases of occupational pneumoconiosis patients diagnosed by institutions qualified for pneumoconiosis diagnosis in Guangzhou from June 1, 1958 to December 31, 2018 were studied. Excluding 258 patients who lacked survival data, 936 patients were included in the pneumoconiosis survival analysis. Life table method was used to estimate the survival rate, Kaplan-Meier method was used to draw the survival curve, log-rank test was used to compare the groups, and Cox proportional risk regression model was used to analyze the influencing factors of survival.Results:The 10, 20 and 30 years cumulative survival rates of pneumoconiosis patients in Guangzhou were 62.8%, 35.2% and 15.4%, respectively. The median survival time was 19.4 years. log-rank test showed that there were statistically significant differences in the survival curves of pneumoconiosis patients between group without tuberculosis and group with tuberculosis ( P<0.001), and there were statistically significant differences among different stages and categories of pneumoconiosis ( P<0.001). Age of exposure to dust ( HR=1.03, 95% CI: 1.01-1.05), age of diagnosis ( HR=1.02, 95% CI: 1.00-1.04), combined pulmonary tuberculosis ( HR=1.46, 95% CI: 1.18-1.81), stage of pneumoconiosis (stage Ⅲ vs. stage Ⅰ, HR=2.26, 95% CI: 1.47-3.48) and categories of pneumoconiosis (fibrogenic mineral dust pneumoconiosis and metallogenic pneumoconiosis, HR=2.45, 95% CI: 1.61-3.74; non-fibrogenic mineral pneumoconiosis and metallogenic pneumoconiosis, HR=2.67, 95% CI: 1.47-4.87; mixed pneumoconiosis and metallogenic pneumoconiosis, HR=2.25, 95% CI: 1.11-4.56) were the factors affecting the survival time of pneumoconiosis patients ( P<0.05) . Conclusion:Pulmonary tuberculosis may increase the risk of death in patients with pneumoconiosis. Mineral dust pneumoconiosis, mixed pneumoconiosis and stage Ⅲ pneumoconiosis may also have higher risk of death.
9.Exploring the Components and Mechanism of Shenbai Jiedu Decoction in Treating CRA Carcinogenesis Based on LC-MS and Network Pharmacology
Li LIU ; Qiuying YAN ; Xiaoxuan FAN ; Minmin FAN ; Liu LI ; Huiping TAO-LI ; Shuchen CHANG ; Haibo CHENG ; Dongdong SUN
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(8):771-784
OBJECTIVE To identify the chemical components of Shenbai Jiedu Decoction(SBJDD),a traditional Chinese medi-cine(TCM)prescription clinically used for the treatment of colorectal adenoma(CRA),and explore the potential mechanism of SBJDD preventing and treating CRA carcinogenesis.METHODS An ultra-high performance liquid chromatography-time of flight-mass spectrometry(UPLC-Q-TOF-MS)method was established to detect the chemical components in the decoction of SBJDD and the plas-ma samples of rats after administration with SBJDD.Based on the network pharmacological method,SBJDD was screened for the poten-tial active ingredients at different stages of CRA carcinogenesis,and the mechanism of the anti-cancer effect of SBJDD was explored.In vitro experiments were also carried out to verify the mechanism of anti-colorectal cancer(CRC)action of SBJDD.RE-SULTS The detection data of UPLC-Q-TOF-MS showed that 152 components were found from SBJDD water extraction.41 chemical compounds were identified in plasma samples from rats administrated with SBJDD.Network pharmacology analysis indicated that during the CREI stage,the potential active ingredients in SBJDD,including epiberberine,and kushenol H,might affect target proteins such as PIK3CA,MAPK3 and PIK3CB.This,in turn,can influence signaling pathways like PI3K-AKT and Ras signaling pathways,and regulate biological processes like protein phosphorylation,and signal transduction.During the CRA stage,the potential active ingredi-ents from SBJDD,such as 3,7-dihydroxycoumarin,palmatine,and kushenol A,might affect target proteins such as AKT and EGFR.This can regulate the negative regulation of apoptotic process,and positive regulation of cell proliferation,and modify HIF-1,and Rap1 signaling pathways.During the progression of CRA carcinogenesis,potential active ingredients such as 3,7-dihydroxycouma-rin may interact with TP53,and impact the PI3K-AKT,and Thyroid hormone signaling pathways to regulate biological processes,in-cluding positive regulation of transcription from RNA polymerase Ⅱ promoter,and negative regulation of apoptotic process.In the CRC stage,core ingredients like p-coumaric acid may bind with proteins such as PRKCB.This binding may impact the signaling pathways that negatively affect EGFR tyrosine kinase inhibitor resistance,and PI3K-AKT signaling pathways.Additionally,it may regulate bio-logical processes,including negative regulation of apoptotic process,signal transduction,and protein phosphorylation.In vitro experi-ment results indicated that SBJDD inhibited the proliferation of HT29 cells and suppressed the expression of EGFR and PKC proteins.CONCLUSION The UPLC-Q-TOF-MS method is established to effectively separate the chemical constituents in SBJDD,which are mainly composed of alkaloids,organic acids and flavonoids components.Components from SBJDD dock with different targets during the carcinogenesis process of CRA and regulate cancer-related signaling pathways to exert therapeutic effects.
10.Immune reconstitution and influencing factors in HIV infected men who have sex with men with access to antiviral therapy in Guangxi Zhuang Autonomous Region from 2005 to 2021
Ni CHEN ; He JIANG ; Huanhuan CHEN ; Qiuying ZHU ; Xiuling WU ; Jianjun LI ; Nengxiu LIANG ; Qin MENG ; Xuanhua LIU ; Jinghua HUANG ; Wenxuan HOU ; Zhaoquan WANG ; Guanghua LAN
Chinese Journal of Epidemiology 2024;45(4):529-535
Objective:To analyze immune reconstitution and influencing factors in HIV infected men who have sex with men (MSM) with access to antiviral therapy (ART) in Guangxi Zhuang Autonomous Region (Guangxi) during 2005-2021.Methods:The data were collected from Chinese Disease Prevention and Control Information System. The study subjects were HIV infected MSM with access to the initial ART for ≥24 weeks in Guangxi from 2005 to 2021 and HIV RNA lower than the detection limit within 24 months. The proportion of infected MSM who had immune reconstitution after ART was calculated. Cox proportional hazard regression model was used to analyze the influencing factors of immune reconstitution. Software SPSS 24.0 was used for statistical analysis.Results:A total of 3 200 HIV infected MSM were enrolled, in whom 15.56 % (498/3 200) had no immune reconstitution, 14.78% (473/3 200) had moderate immune reconstitution, and the rate of complete immune reconstitution was 69.66% (2 229/3 200). The M ( Q1, Q3) of ART time for immune reconstitution was 12 (5, 27) months. Multivariate Cox proportional risk regression model analysis results showed that compared with those with initial ART at age ≥30 years, WHO clinical stage Ⅲ/Ⅳ illness, baseline BMI <18.50 kg/m 2 and baseline CD4 +T lymphocyte (CD4) counts <200 cells/μl, HIV infected MSM with initial ART at age <30 years, WHO clinical stageⅠ/Ⅱ illness, baseline BMI≥24.00 kg/m 2 and baseline CD4 counts ≥200 cells/μl were more likely to have complete immune reconstitution. Conclusions:In the HIV infected MSM in Guangxi, failures to achieve moderate and complete immune reconstitution were observed. Surveillance and ART regimen should be improved for key populations, such as those with older age and low baseline CD4 counts.

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