1.Intra-and peri-tumoral radiomics model for predicting the response to concurrent chemoradiotherapy in cervical squamous cell carcinoma based on dynamic contrast-enhanced MRI
Yaying SU ; Dan ZHAO ; Zhiying PANG ; Fei YANG ; Shujun CUI
Journal of Practical Radiology 2024;40(3):411-416
Objective To investigate the correlation between intra-and peri-tumoral radiomics features and the response to con-current chemoradiotherapy(CCRT)in cervical squamous cell carcinoma,and to explore the difference of predictive performance between 2D and 3D radiomics models.Methods The imaging data of 132 patients were analyzed retrospectively and randomly divided into training set(n=92)and validation set(n=40).Radiomics features were extracted based on the dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI),the correlation analysis and least absolute shrinkage and selection operator(LASSO)algorithm were used for dimensionality reduction and screening,then the radiomics score was calculated and the logistic model was constructed.The receiver operating characteristic(ROC)curve,internal validation of Bootstrap and Brier score were used to evaluate the discrimina-tion and calibration of the model,and the improvement in predictive performance of 3D model compared with 2D model was evaluated by the integrated discrimination improvement(IDI).Results In the training set,the ROC curve showed that the area under the curve(AUC)of the models(2D-intratumoral,3D-intratumoral,3D-peritumoral,3D-combined)ranged from 0.774 to 0.893.The internal validation of Bootstrap showed the AUC were 0.772,0.860,0.847 and 0.888,respectively,while in the validation set,the AUC were 0.757,0.849,0.824 and 0.887,respectively.The Brier scores indicated that the models were well calibrated.In the training set and the validation set,the IDI values were 0.155 and 0.179,respectively,and the differences were statistically significant(P<0.05).Conclusion The radiomics analysis based on the tumor volume can fully explore the tumor heterogeneity.The intra-and peri-tumoral radiomics combined model shows the best predictive performance,which is important to assist clinicians in developing individualized therapies.
2.Construction of a Quality Control System for Oncology Medical Records Based on Natural Language Processing
Weiwei LIU ; Lijun WANG ; Juan PANG ; Dan WANG ; Fanxiu HENG
Journal of Medical Informatics 2024;45(2):77-81,91
Purpose/Significance Through the establishment of a quality control system for electronic medical record(EMR)con-tent,the standardization and normalization of medical record writing is realized,and the quality of hospital medical record is improved.Method/Process The intelligent medical data center is built based on hospital medical data,and the knowledge base and rule base with tumor specialty characteristics are formed by combining natural language processing(NLP)and machine learning technology.The new quality control mode of"pre-audit,comprehensive coverage,process supervision and closed-loop management"of EMR is realized.Result/Conclusion After the application of the medical record quality control system based on NLP,the quality control coverage rate in-creased from 1%to 100%,and the rate of class A medical records increased to more than 96%,with good real-time and accuracy,providing a solid information foundation for the high-quality development of hospital medical records.
3.Clinical trial of rituximab and leflunomide in the treatment of patients with systemic lupus erythematosus
Jia-Hui GUO ; Jun-Jie ZOU ; Yang-Yang WANG ; Jin-Long ZHANG ; Dan-Dan PANG ; Xiao-Yan XU
The Chinese Journal of Clinical Pharmacology 2024;40(11):1547-1550
Objective To observe the clinical efficacy and safety of rituximab injection combined with leflunomide tablets in the treatment of patients with systemic lupus erythematosus(SLE).Methods The SLE patients were divided into control and treatment groups according to cohort method.The control group received leflunomide with 50 mg·d-1 after meal in the first 3 days of treatment and was adjusted to 20 mg·d-1 thereafter.On the basis of control group,the treatment group was combined with rituximab,375 mg·m-2 was given intravenously every 2 weeks in the first 3 times of treatment,and adjusted to once every 4 weeks from the 4th dose.Two groups were treated for 24 weeks.The clinical efficacy,systemic lupus erythematosus disease activity index(SLEDAI)scores,serological indicators,24-hour urinary protein and adverse drug reactions were compared between two groups.Results The treatment and control groups were enrolled 74 cases and 72 cases,respectively.After treatment,the total effective rates of treatment and control groups were 91.89%(68 cases/74 cases)and 79.17%(57 cases/72 cases)with significant difference(P<0.05).After treatment,the SLEDAI scores of treatment and control groups were(7.21±1.67)and(9.03±1.35)points;the levels of anti-Smith/ribonucleoprotein antibodies were(81.43±18.25)and(59.38±14.61)U·mL-1;the levels of immunoglobulin G were(12.04±2.15)and(17.28±2.64)g·L-1;the levels of interleukin-10 were(33.39±7.13)and(39.87±9.02)pg·mL-1;24-hour urinary protein quantification were(1.46±0.32)and(2.67±0.54)g·24 h-1;all the differences were statistically significant(all P<0.05).The drug adverse reactions of two groups were liver and kidney function injury and digestive tract reactions.The total incidences of drug adverse reactions in the treatment and control groups were 13.51%and 5.56%without significant difference(P>0.05).Conclusion Rituximab injection combined with leflunomide tablets has a definitive clinical efficacy in the treatment of SLE patients,which can significantly reduce disease activity and inflammatory reactions,improve immune function,without increasing the incidence of drug adverse reactions.
4.Changes in the Non-targeted Metabolomic Profile of Three-year-old Toddlers with Elevated Exposure to Polycyclic Aromatic Hydrocarbons
Yang LI ; Dan LIN ; Qin Xiu ZHANG ; Xiu Guang JU ; Ya SU ; Qian ZHANG ; Ping Hai DUAN ; Sen Wei YU ; Ling Bing WANG ; Tao Shu PANG
Biomedical and Environmental Sciences 2024;37(5):479-493
Objective To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons(PAHs)during critical brain development and explore their potential link with the intestinal microbiota. Methods Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs(OH-PAHs)in 36-month-old children.Subsequently,37 children were categorized into low-and high-exposure groups based on the sum of the ten OH-PAHs.Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine samples.Furthermore,fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina MiSeq. Results The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group(variable importance for projection>1,P<0.05).Most of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene,fluorine,and phenanthrene(r=0.336-0.531).The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states,including amino acid,lipid,and nucleotide metabolism.Additionally,these distinct metabolites were significantly associated with specific intestinal flora abundances(r=0.34-0.55),which were mainly involved in neurodevelopment. Conclusion Higher PAH exposure in young children affected metabolic homeostasis,particularly that of certain gut microbiota-derived metabolites.Further investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.
5.Association between waist circumference and ischemic stroke: a prospective study in adults from Qingdao
Yuhui LI ; Lei LIU ; Dan HU ; Xiaoyan ZHENG ; Jun LYU ; Canqing YU ; Pei PEI ; Haiping DUAN ; Ruqin GAO ; Zengchang PANG ; Xiaocao TIAN ; Dianjianyi SUN
Chinese Journal of Epidemiology 2024;45(2):178-184
Objective:To analyze the association between waist circumference (WC) and ischemic stroke (IS).Methods:The data for the present study were from the prospective cohort study of China Kadoorie Biobank in Qingdao. Using baseline information and IS events of the participants, the Cox proportional hazard regression model and restricted cubic spline (RCS) were used to analyze the association between WC and IS.Results:A total of 33 355 participants were included in the study, with 302 008.88 person-years of follow-up. A total of 1 093 new cases of IS were observed. Multivariate Cox proportional hazard regression model analysis showed that compared to the respondents with normal WC (male <85.0 cm, female <80.0 cm), respondents with excessive WC (male ≥85.0 cm, female ≥80.0 cm) had a 78% higher risk of IS incidence [hazard ratio( HR)=1.78, 95% CI: 1.51-2.10], and the risk increased by 72% ( HR=1.72, 95% CI: 1.40-2.12) and 83% ( HR=1.83, 95% CI: 1.40-2.39) in men and women. According to the RCS, the increase in WC and the risk of IS showed an "S" trend of nonlinear dose-response relationship. Conclusions:The risk of IS would increase with the WC. Keeping a normal WC is important for preventing IS.
6.Association of solid fuel use for heating and smoking with respiratory diseases: a prospective cohort study
Yang YU ; Xiaocao TIAN ; Hua ZHANG ; Dan HU ; Jun LYU ; Canqing YU ; Pei PEI ; Dianjianyi SUN ; Ruqin GAO ; Zengchang PANG ; Haiping DUAN
Chinese Journal of Epidemiology 2024;45(10):1356-1361
Objective:To investigate the association between solid fuel use for heating, smoking, and respiratory diseases.Methods:This study is based on the Qingdao project of the China Kadoorie Biobank. After screening, 26 165 individuals were included in the study. We employed Cox proportional hazards regression models, stratified by risk age (in 5-year intervals) and sex while adjusting for confounding variables such as occupation and physical activity level to analyze the association between solid fuel use for heating, smoking, and increased risk of respiratory diseases.Results:Among the 26 165 participants, the average age of those using solid fuel for heating was (52.57±10.31) years, with females constituting 58.04% and former/current smokers accounting for 65.38%. The results indicated that both the solid fuel group and the former/current smoking group had a higher risk of respiratory diseases, with hazard ratios ( HR) (95% CI) of 1.21 (1.04-1.41) and 1.41 (1.16-1.71), respectively. For the duration of solid fuel use, the HR (95% CI) for 20 years or more, it was 1.27 (1.07-1.51). The multiplicative interaction term between solid fuel use and smoking was statistically significant. Conclusions:The use of solid fuel for heating and smoking significantly increases the risk of respiratory diseases, and there may be a multiplicative interaction between solid fuel use and smoking.
7.Progress of circulating tumor DNA methylation for gastric cancer screening and management
Qinxing CAO ; Li YAN ; Nengyi HOU ; Jinfeng CHEN ; Song YU ; Hejiang LU ; Zhenjia DAN ; Minghui PANG
Chinese Journal of Gastrointestinal Surgery 2024;27(5):535-544
Circulating tumor DNA (ctDNA) is cell-free DNA released by tumors or circulating tumor cells, containing abundant tumor-specific information that can serve as biomarkers for cancer early screening, monitoring, prognosis, and prediction of treatment response. This is particularly attractive in the field of gastric cancer, where high-quality screening, monitoring, and prediction methods are currently lacking. Gastric cancer exhibits significant tumor heterogeneity, with large differences in genetic and epigenetic characteristics among different subgroups. Methylated ctDNA has high sensitivity and specificity, which can help clarify tumor genotyping and facilitate the formulation of precise diagnostic and therapeutic strategies. Furthermore, numerous studies have confirmed the unique advantages of methylated DNA in predicting treatment response, adjuvant therapy, and drug resistance assessment, which may be used in the future to enhance the efficacy of chemotherapy regimens and improve patient chemotherapeutic response, and even treat multidrug resistance. However, there are several challenges associated with methylated ctDNA, such as low sensitivity and specificity at single-target sites, limited association between some gastric cancer subtypes and ctDNA, off-target risks, and the lack of large-scale and high-quality clinical research evidence. This review mainly summarizes current research on the methylation status of ctDNA in gastric cancer and connects these findings to early screening, recurrence monitoring, and potential treatment opportunities for gastric cancer. With advances in technology and the deepening of interdisciplinary research, ctDNA detection will reveal more disease information and become an essential foundation for gastric cancer research and precision medicine treatment.
8.Progress of circulating tumor DNA methylation for gastric cancer screening and management
Qinxing CAO ; Li YAN ; Nengyi HOU ; Jinfeng CHEN ; Song YU ; Hejiang LU ; Zhenjia DAN ; Minghui PANG
Chinese Journal of Gastrointestinal Surgery 2024;27(5):535-544
Circulating tumor DNA (ctDNA) is cell-free DNA released by tumors or circulating tumor cells, containing abundant tumor-specific information that can serve as biomarkers for cancer early screening, monitoring, prognosis, and prediction of treatment response. This is particularly attractive in the field of gastric cancer, where high-quality screening, monitoring, and prediction methods are currently lacking. Gastric cancer exhibits significant tumor heterogeneity, with large differences in genetic and epigenetic characteristics among different subgroups. Methylated ctDNA has high sensitivity and specificity, which can help clarify tumor genotyping and facilitate the formulation of precise diagnostic and therapeutic strategies. Furthermore, numerous studies have confirmed the unique advantages of methylated DNA in predicting treatment response, adjuvant therapy, and drug resistance assessment, which may be used in the future to enhance the efficacy of chemotherapy regimens and improve patient chemotherapeutic response, and even treat multidrug resistance. However, there are several challenges associated with methylated ctDNA, such as low sensitivity and specificity at single-target sites, limited association between some gastric cancer subtypes and ctDNA, off-target risks, and the lack of large-scale and high-quality clinical research evidence. This review mainly summarizes current research on the methylation status of ctDNA in gastric cancer and connects these findings to early screening, recurrence monitoring, and potential treatment opportunities for gastric cancer. With advances in technology and the deepening of interdisciplinary research, ctDNA detection will reveal more disease information and become an essential foundation for gastric cancer research and precision medicine treatment.
9.Expression of UBE2C in liver cancer tissues and its effect on proliferation and invasion of hepatocellular carcinoma cells HepG2
Ping ZHAO ; Dan PANG ; Xi-Zeng ZHU ; Hai-Xia SHAN ; Hui-Wen JIA
Chinese Journal of Current Advances in General Surgery 2024;27(7):511-516
Objective:To investigate the expression level of UBE2C in liver cancer tissues and its effect on the proliferation and invasion of hepatocellular carcinoma cells HepG2 after UBE2C silencing.Methods:The data set of liver cancer was downloaded from the TCGA database.Ac-cording to the median expression level of UBE2C mRNA in liver cancer tissues,all liver cancer pa-tients were divided into UBE2C higher(n=169)and lower expression group(n=205),respectively.The expression level of UBE2C mRNA in liver cancer tissues and its relationship with the patients prognosis was analyzed.COX regression was used to analyze the influencing factors of the liver cancer patients prognosis.The human hepatocellular carcinoma cell lines(HepG2,Huh7 and SMMC-7721)and human nromal hepatic epithelial cell line(THLE-3)were selected,and the ex-pression level of UBE2C in the four cell lines were detected by Western blot and real-time fluores-cence quantitative PCR,respectively.The HepG2 cell line was protein and mRNA expression leves divided into control group,NC group and si-UBE2C group according to UBE2C silencing.The ef-fects of UBE2C silencing on proliferation and invasion of HepG2 cell line were analyzed.Results:The expression level of UBE2C mRNA in liver cancer tissues and adjacent normal liver tissues were 4.342(3.239,5.635)and 0.905(0.587,1.230),respectively.Compared with adjacent normal liver tissues,UBE2C mRNA levels in liver cancer tissues were significantly higher(P<0.001).The UBE2C mRNA expression levels in liver cancer tissues and paired adjacent normal liver tissues were 4.266(3.342,5.054)and 0905(0.587,1.230),respectively.Compared with paired adjacent normal liver tissues,UBE2C mRNA expression levels in liver cancer tissues were significantly higher(P<0.001).The median survival time of UBE2C mRNA higher and lower expression groups was 48.85 months and 69.38 months.Compared with the lower expression group,the median survival time of UBE2C mRNA higher expression group was significantly shortened(P=0.045).T staging(T3/T4)and UBE2C expression(higher expression)were independent risk factors for poor prognosis in patients with liver cancer(P<0.05).Compared with human liver epithelial cell line THLE-3,UBE2C protein and mRNA were significantly higher expressed in human hepatocellular carcinoma cell line HepG2,Huh7 and SMMC-7721(P<0.05).The expression level of UBE2C protein and mRNA expression was the most significant in human hepatocellular carcinoma cell line HepG2 relative to cell line Huh7 and SMMC-7721.The CCK-8 results show that the cell proliferation rate in si-UBE2C group were significantly decreased protein and mRNA expression levels compared to control group and NC group at 72 h and 96 h,and the differences were significant(P<0.05).The number of invasive cells in control group,NC group and si-UBE2C group were(23.12±3.45),(24.33±2.83)and(10.21±1.14),respectively.Compared with control group and NC group,the number of invasive cells in si-UBE2C group was significantly decreased(P<0.05).Conclusion:UBE2C was higher expressed in liver cancer,and can be used as a biomarker for poor prognosis of patients with liver cancer.After silencing of UBE2C gene can significantly inhibit proliferation and invasion of HepG2.
10.Minimal improvement in coronary artery disease risk prediction in Chinese population using polygenic risk scores: evidence from the China Kadoorie Biobank.
Songchun YANG ; Dong SUN ; Zhijia SUN ; Canqing YU ; Yu GUO ; Jiahui SI ; Dianjianyi SUN ; Yuanjie PANG ; Pei PEI ; Ling YANG ; Iona Y MILLWOOD ; Robin G WALTERS ; Yiping CHEN ; Huaidong DU ; Zengchang PANG ; Dan SCHMIDT ; Rebecca STEVENS ; Robert CLARKE ; Junshi CHEN ; Zhengming CHEN ; Jun LV ; Liming LI
Chinese Medical Journal 2023;136(20):2476-2483
BACKGROUND:
Several studies have reported that polygenic risk scores (PRSs) can enhance risk prediction of coronary artery disease (CAD) in European populations. However, research on this topic is far from sufficient in non-European countries, including China. We aimed to evaluate the potential of PRS for predicting CAD for primary prevention in the Chinese population.
METHODS:
Participants with genome-wide genotypic data from the China Kadoorie Biobank were divided into training ( n = 28,490) and testing sets ( n = 72,150). Ten previously developed PRSs were evaluated, and new ones were developed using clumping and thresholding or LDpred method. The PRS showing the strongest association with CAD in the training set was selected to further evaluate its effects on improving the traditional CAD risk-prediction model in the testing set. Genetic risk was computed by summing the product of the weights and allele dosages across genome-wide single-nucleotide polymorphisms. Prediction of the 10-year first CAD events was assessed using hazard ratios (HRs) and measures of model discrimination, calibration, and net reclassification improvement (NRI). Hard CAD (nonfatal I21-I23 and fatal I20-I25) and soft CAD (all fatal or nonfatal I20-I25) were analyzed separately.
RESULTS:
In the testing set, 1214 hard and 7201 soft CAD cases were documented during a mean follow-up of 11.2 years. The HR per standard deviation of the optimal PRS was 1.26 (95% CI:1.19-1.33) for hard CAD. Based on a traditional CAD risk prediction model containing only non-laboratory-based information, the addition of PRS for hard CAD increased Harrell's C index by 0.001 (-0.001 to 0.003) in women and 0.003 (0.001 to 0.005) in men. Among the different high-risk thresholds ranging from 1% to 10%, the highest categorical NRI was 3.2% (95% CI: 0.4-6.0%) at a high-risk threshold of 10.0% in women. The association of the PRS with soft CAD was much weaker than with hard CAD, leading to minimal or no improvement in the soft CAD model.
CONCLUSIONS
In this Chinese population sample, the current PRSs minimally changed risk discrimination and offered little improvement in risk stratification for soft CAD. Therefore, this may not be suitable for promoting genetic screening in the general Chinese population to improve CAD risk prediction.
Male
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Humans
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Female
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Coronary Artery Disease/genetics*
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Biological Specimen Banks
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East Asian People
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Risk Assessment/methods*
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Genetic Predisposition to Disease/genetics*
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Risk Factors
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Genome-Wide Association Study

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