1.Lipidomics Combined with Machine Learning for Screening Biomarkers of Early-Stage Lung Cancer in the Elderly
Qing WANG ; Yue HE ; Xu LIU ; Zifan LI ; Kezhong CHEN
Medical Journal of Peking Union Medical College Hospital 2026;17(3):652-662
Based on plasma lipidomics combined with machine learning approaches, this study aimed to screen molecular biomarkers for the diagnosis of early-stage lung cancer in elderly patients and to evaluate their diagnostic performance. This was a retrospective diagnostic study consisting of two parts. The first part involved molecular biomarker screening. Elderly patients with early-stage lung cancer (early lung cancer group), patients with benign pulmonary nodules (benign nodule group), and contemporaneous healthy individuals undergoing physical examinations (healthy control group) were enrolled from Peking University People's Hospital between November 2023 and November 2024. In addition, early-stage lung cancer patients and healthy controls meeting the inclusion criteria from a previous study of our research group were included as an independent validation cohort. Plasma samples were collected from all subjects, and untargeted lipidomics analysis was performed using high-performance liquid chromatography-mass spectrometry. Principal component analysis and orthogonal partial least squares discriminant analysis were used to evaluate metabolic differences between groups. L1-regularized support vector machine combined with incremental feature selection was employed to screen diagnostic biomarkers for early-stage lung cancer. Model performance was assessed using receiver operating characteristic curves, calibration curves, Brier scores, and decision curve analysis. The second part involved functional validation of the molecular biomarkers using the human lung adenocarcinoma cell line A549, with palmitoylcarnitine (CAR 16∶0) selected as a representative biomarker for functional validation via CCK-8 and cell scratch assays. A total of 36 patients in the early lung cancer group, 35 patients in the benign nodule group, and 41 healthy controls were enrolled, along with an independent validation cohort of 110 individuals (59 patients with early-stage lung cancer and 51 healthy controls). The principal component analysis results demonstrated that quality control samples were tightly aggregated at the centroid of all samples, reflecting robust instrument performance and dependable data quality.Orthogonal partial least squares discriminant analysis revealed significant metabolic differences between the early lung cancer group and the control group (benign nodule group + healthy control group) (R2X=0.406, R2Y=0.529, Q2Y=0.44). L1-regularized support vector machine identified five carnitine-related lipids-palmitoleoylcarnitine(CAR 16∶1), palmitoylcarnitine, The five plasma carnitine-related lipids screened based on untargeted lipidomics and machine learning may serve as potential molecular biomarkers for the diagnosis of early-stage lung cancer in elderly patients. The high-sensitivity characteristic of the model makes it particularly suitable for screening scenarios in early-stage lung cancer.
2.Analysis of the success rate of CT-Guided 3D printed template-navigated radioactive seed implantation in the treatment of pancreatic cancer
Hongyu LIU ; Yunpeng SHI ; Zifan HE ; Baodong GAI ; Kaixian ZHANG
Chinese Journal of Endocrine Surgery 2025;19(5):790-792
Pancreatic cancer is highly malignant and difficult to treat. The implantation of radioactive seed has opened up a new treatment option for pancreatic cancer. Although the implantation of radioactive seed in the treatment of pancreatic cancer has achieved good results, due to the special anatomical location of pancreatic cancer and the dense distribution of important tissues and organs around the tumor, the operation of seed implantation for pancreatic cancer has become a clinical treatment challenge. We applied the method of 3D printing template navigation and constraining the direction of the puncture needle. The puncture needle followed the safe puncture path designed in the preoperative treatment planning system, effectively avoiding important tissues and organs, and implanted radioactive seeds in the tumor. The operation of seed implantation was simplified, homogenized and made safe. In this group of cases, the proportion of successful particle implantation using 3D printing template navigation was 89.5%. All cases met the preoperative treatment plan in postoperative dose verification and achieved the purpose of radioactive seed implantation treatment.
3.Analysis of the success rate of CT-Guided 3D printed template-navigated radioactive seed implantation in the treatment of pancreatic cancer
Hongyu LIU ; Yunpeng SHI ; Zifan HE ; Baodong GAI ; Kaixian ZHANG
Chinese Journal of Endocrine Surgery 2025;19(5):790-792
Pancreatic cancer is highly malignant and difficult to treat. The implantation of radioactive seed has opened up a new treatment option for pancreatic cancer. Although the implantation of radioactive seed in the treatment of pancreatic cancer has achieved good results, due to the special anatomical location of pancreatic cancer and the dense distribution of important tissues and organs around the tumor, the operation of seed implantation for pancreatic cancer has become a clinical treatment challenge. We applied the method of 3D printing template navigation and constraining the direction of the puncture needle. The puncture needle followed the safe puncture path designed in the preoperative treatment planning system, effectively avoiding important tissues and organs, and implanted radioactive seeds in the tumor. The operation of seed implantation was simplified, homogenized and made safe. In this group of cases, the proportion of successful particle implantation using 3D printing template navigation was 89.5%. All cases met the preoperative treatment plan in postoperative dose verification and achieved the purpose of radioactive seed implantation treatment.
4.Clinical value of transcriptome mRNA sequencing-derived SLC12A1 gene in heart failure patients with mildly reduced or preserved ejection fraction
Mengwei WANG ; Hongfei LIU ; Yunqiang ZHANG ; Ze HOU ; Xinyi WANG ; Yingnan YE ; Zifan WANG ; Yuxin ZHANG ; Kegang JIA
Chinese Journal of Laboratory Medicine 2025;48(8):1071-1079
Objective:To explore the relationship between the differential genes derived from transcriptome mRNA sequencing and prognosis among heart failure patients with mildly reduced ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF).Methods:This was a case-control study. Ten patients with HFmrEF and 10 patients with HFpEF treated at TEDA International Cardiovascular Disease Hospital from November 2021 to January 2022 were selected and differentially expressed genes were screened by transcriptome mRNA sequencing. Ten healthy people served as control group. In addition, 50 patients with HFmrEF, 62 patients with HFpEF, who were treated at TEDA International Cardiovascular Disease Hospital at the same period, were selected as validation groups, 57 healthy people served as control validation group. Real-time quantitative PCR (RT-qPCR) was used to detect the expression of differential genes in each group. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to assess the differential diagnosis and prognostic value of differential genes in these patients. Patients were followed up regularly to document adverse events within 1 year after discharge including cardiac death and readmission for heart failure. Survival analysis was performed using Kaplan-Meier curves and tested by log rank test. Cox regression analysis was used to explore whether differential mRNA was risk factors for poor prognosis in HFmrEF and HFpEF patients.Results:A total of four genes were differentially expressed (three upregulated and one downregulated gene) between the HFmrEF group and HFpEF group (adjust P<0.05). SLC12A1, C15orf48 and SPP1 were associated with the progress of cardiovascular disease, and selected for validation in the clinical cohort. RT-qPCR results showed that the gene expression of SLC12A1 in the HFmrEF group was significantly higher than that in the HFpEF group ( P<0.001). The AUC for the adjunctive differential diagnostic value of SLC12A1 for HFmrEF and HFpEF was 0.802 ( P<0.001) and the AUC of SLC12A1 with a cut-off value of 6.634 was 0.737 ( P=0.003) in determining poor prognosis in patients with HFpEF. Kaplan-Meier survival analysis showed that patients with SLC12A1≤6.634 had a higher incidence of adverse cardiac events than patients with SLC12A1 >6.634 ( P=0.001). Cox regression analysis showed that the risk of adverse cardiac events in the SLC12A1 ≤6.634 group was 6.787 times higher than in the SLC12A1 >6.634 group ( HR=6.787, P=0.011). Conclusions:Transcriptome mRNA sequencing analysis is valuable for detecting clinical relevant differentially expressed genes in HFmrEF and HFpEF patients, among which SLC12A1 can be used as a novel molecular biomarker to aid the differential diagnosis of HFmrEF and HFpEF. In addition, SLC12A1 may be used as an adjunctive biomarker for the prognosis evaluation in patients with HFpEF.
5.Safety evaluation of therapeutic plasma exchange in patients with lower hematocrit levels
Ying LI ; Yuanming YANG ; Zifan MENG ; Zheng LIU ; Haiyan WANG
Chinese Journal of Blood Transfusion 2025;38(5):699-703
Objective: To retrospectively assess whether a lower hematocrit level (between 18% and 20%) had any impact on the safety of patients undergoing therapeutic plasma exchange (TPE), and to further determine the threshold for red blood cell supplementation prior to TPE. Methods: Clinical data from 181 adult patients who underwent TPE treatment at the Department of Blood Transfusion of our hospital from March 2023 to July 2024 were collected. The patients were divided into a study group of 44 patients (Hct ≥18% and <20%) and a control group of 137 patients (Hct≥20%). In two groups, blood volume-related safety indicators including respiration rate, heart rate, systolic blood pressure, and blood oxygen saturation levels before and after TPE were compared using t-test. Between-group differences in the grading of adverse reactions such as allergies and hypotension were analyzed using chi-square test. Results: A total of 659 TPE treatments were performed on 181 patients, with 169 TPE treatments on 44 patients in the study group (Hct≥18% and <20%) and 490 TPE treatments on 137 patients in the control group (Hct≥20%). There were no statistically significant differences in age, gender, BMI category, and the presence of cardiac insufficiency between the two groups. In the study group, there were no statistically significant differences in safety indicators such as respiration rate, heart rate, systolic blood pressure, and blood oxygen saturation level before and after TPE. In the control group, there were no statistically significant differences in heart rate and systolic blood pressure before and after TPE, but there were statistically significant differences in respiration rate and blood oxygen saturation level (P<0.05). There were no statistically significant differences in the grading of adverse reactions such as allergic reactions and hypotension between the two groups. Conclusion: For adult patients with stable conditions, maintaining a lower hematocrit level (Hct ≥18% and <20%) during TPE is relatively safe. It is feasible to lower the TPE red blood cell supplementation threshold to 18%≤Hct<20%,which may save blood resources while potentially benefit patients by avoiding unnecessary red blood cell transfusion.
6.Clinical value of transcriptome mRNA sequencing-derived SLC12A1 gene in heart failure patients with mildly reduced or preserved ejection fraction
Mengwei WANG ; Hongfei LIU ; Yunqiang ZHANG ; Ze HOU ; Xinyi WANG ; Yingnan YE ; Zifan WANG ; Yuxin ZHANG ; Kegang JIA
Chinese Journal of Laboratory Medicine 2025;48(8):1071-1079
Objective:To explore the relationship between the differential genes derived from transcriptome mRNA sequencing and prognosis among heart failure patients with mildly reduced ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF).Methods:This was a case-control study. Ten patients with HFmrEF and 10 patients with HFpEF treated at TEDA International Cardiovascular Disease Hospital from November 2021 to January 2022 were selected and differentially expressed genes were screened by transcriptome mRNA sequencing. Ten healthy people served as control group. In addition, 50 patients with HFmrEF, 62 patients with HFpEF, who were treated at TEDA International Cardiovascular Disease Hospital at the same period, were selected as validation groups, 57 healthy people served as control validation group. Real-time quantitative PCR (RT-qPCR) was used to detect the expression of differential genes in each group. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to assess the differential diagnosis and prognostic value of differential genes in these patients. Patients were followed up regularly to document adverse events within 1 year after discharge including cardiac death and readmission for heart failure. Survival analysis was performed using Kaplan-Meier curves and tested by log rank test. Cox regression analysis was used to explore whether differential mRNA was risk factors for poor prognosis in HFmrEF and HFpEF patients.Results:A total of four genes were differentially expressed (three upregulated and one downregulated gene) between the HFmrEF group and HFpEF group (adjust P<0.05). SLC12A1, C15orf48 and SPP1 were associated with the progress of cardiovascular disease, and selected for validation in the clinical cohort. RT-qPCR results showed that the gene expression of SLC12A1 in the HFmrEF group was significantly higher than that in the HFpEF group ( P<0.001). The AUC for the adjunctive differential diagnostic value of SLC12A1 for HFmrEF and HFpEF was 0.802 ( P<0.001) and the AUC of SLC12A1 with a cut-off value of 6.634 was 0.737 ( P=0.003) in determining poor prognosis in patients with HFpEF. Kaplan-Meier survival analysis showed that patients with SLC12A1≤6.634 had a higher incidence of adverse cardiac events than patients with SLC12A1 >6.634 ( P=0.001). Cox regression analysis showed that the risk of adverse cardiac events in the SLC12A1 ≤6.634 group was 6.787 times higher than in the SLC12A1 >6.634 group ( HR=6.787, P=0.011). Conclusions:Transcriptome mRNA sequencing analysis is valuable for detecting clinical relevant differentially expressed genes in HFmrEF and HFpEF patients, among which SLC12A1 can be used as a novel molecular biomarker to aid the differential diagnosis of HFmrEF and HFpEF. In addition, SLC12A1 may be used as an adjunctive biomarker for the prognosis evaluation in patients with HFpEF.
7.Signals mining and analysis of adverse drug events of exenatide based on FAERS database
Qiyao ZHAO ; Yan LIU ; Tianyi YANG ; Jiaoyue LI ; Yunpeng LUO ; Ping LI ; Jinlin DAI ; Zifan HUANG ; Li ZHANG ; Xiaohui YANG
Chinese Journal of Pharmacoepidemiology 2024;33(12):1355-1364
Objective To analyze adverse drug event(ADE)signals associated with exenatide based on data from the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS),and to provide insights for rational medication use in clinical settings.Methods ADE reports of exenatide as the primary suspected drug were obtained by collecting the data of FAERS database from the first quarter 2014 to the second quarter 2024.ADE signals were analyzed by joint reporting odds ratio(ROR)method,proportional reporting odds ratio(PRR)method,Bayesian confidence interval progressive neural network(BCPNN)method and multi-item gamma Poisson shrinker(MGPS)method.Results After data cleaning,118 745 reports of exenatide-related ADEs were collected.These ADEs spanned 14 system-organ classes and involved 185 preferred terms.Commonly reported ADEs included reactions at the injection site,hypoglycemia,reduced appetite,and cholelithiasis.Severe ADEs were primarily cases of acute pancreatitis,in consistent with the drug's labeling.Moreover,the instructions did not record ADE signals of pancreatic cancer,thyroiditis,and reduced frustration tolerance.Conclusion Prescription of the exenatide should be vigilant about the signals not listed on the product labeling,such as pancreatic cancer,thyroid cancer,and decreased frustration tolerance,to improve the safety of medication use in patients.
8.Signals mining and analysis of adverse drug events of pioglitazone based on FAERS database
Ping LI ; Yan LIU ; Tianyi YANG ; Qiyao ZHAO ; Jiaoyue LI ; Yunpeng LUO ; Jinlin DAI ; Zifan HUANG ; Li ZHANG ; Xiaohui YANG
Chinese Journal of Pharmacoepidemiology 2024;33(12):1365-1374
Objective To mine adverse drug event(ADE)signals of pioglitazone,and to provide references for the safe clinical use of the medication.Methods The reporting odds ratio(ROR)method and the Bayesian confidence propagation neural network(BCPNN)method were utilized to analyze pioglitazone ADE reports from the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database,spanning from the first quarter of 2013 to the second quarter of 2024.Results After data cleaning,a total of 16 904 pioglitazone ADE reports were retrieved.The ADE reports primarily involved individuals over the age of 45,with a male predominance,and were mainly reported from the United States.After screening,180 ADE signals were identified,affecting 27 system-organ classes(SOC).Out of these,34 ADE signals were classified as medium to high risk,with 9 ADE signals not mentioned in the product labeling,including ureteral cancer,urethral cancer,gallbladder tumors,malignant tumors of the renal pelvis,pericardial tamponade,left ventricular dysfunction,pulmonary edema,cystitis,and somniloquy.Conclusion In addition to closely monitoring weight gain,systemic edema,and heart failure,clinical attention should be given to left ventricular dysfunction,pulmonary edema,cystitis,and pericardial tamponade ADEs that are not mentioned in the instructions,to ensure the safety of pioglitazone use in clinical practice.
9.Signals mining and analysis of adverse drug events of lixisenatide based on FAERS database
Jinlin DAI ; Yan LIU ; Tianyi YANG ; Jiaoyue LI ; Zifan HUANG ; Yunpeng LUO ; Ping LI ; Qiyao ZHAO ; Li ZHANG ; Xiaohui YANG
Chinese Journal of Pharmacoepidemiology 2024;33(12):1325-1335
Objective To investigate post-marketing adverse drug event(ADE)signals associated with lixisenatide,and to provide guidance for safe clinical use.Methods The ADE reporting data of lixisenatide ADE were mined and the signals were detected from the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database from the first quarter 2013 to the second quarter 2024 using the reporting odds ratio(ROR)method and Bayesian confidence propagation neural network(BCPNN)method.Results After data cleaning,a total of 5 162 ADE reports with lixisenatide as the primary suspected drug were collected.The 85 ADE signals identified by the two statistical analysis methods,affected 14 system-organ classes(SOC).They were primarily concentrated in injuries,poisonings,and procedural complications(25.88%),various examinations(14.12%),systemic diseases and reactions at administration sites(14.12%),gastrointestinal diseases(9.41%),and various neurological diseases(5.88%).There were 28 ADE signals such as pancreatitis,visual impairment,and color blindness,that were not included in the drug instructions.Conclusion In addition to monitoring for common ADE associated with GLP-1 receptor agonists such as hypoglycemia,gastrointestinal,and neurological effects,clinicians should also be vigilant for underlying ADE like pancreatic-related diseases,eye toxicity reaction when using lixisenatide to ensure safe and rational medication use.
10.Signals mining and analysis of adverse drug events of dapagliflozin based on FAERS database
Jiaoyue LI ; Yan LIU ; Qiubo YANG ; Tianyi YANG ; Jinlin DAI ; Qiyao ZHAO ; Yunpeng LUO ; Ping LI ; Zifan HUANG ; Li ZHANG ; Xiaohui YANG
Chinese Journal of Pharmacoepidemiology 2024;33(12):1336-1345
bjective To mine signals of post-marketing adverse drug events(ADEs)associated with dapagliflozin,and to provide insights for safe medication in clinical settings.Methods Data on ADEs related to dapagliflozin from U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)were collected from the first quarter of 2013 to the third quarter of 2024.The analyses involved data mining and signal monitoring using disproportionality analysis techniques including the reporting odds ratio(ROR)method,Medicines and Healthcare Products Regulatory Agency(MHRA)method,Bayesian confidence propagation neural network(BCPNN)method,and multi-item gamma Poisson shrinker(MGPS)method.Results After data cleaning,a total of 55 832 qualified dapagliflozin case reports were obtained,involving 25 090 patients,with a slightly higher percentage of males(44.99%)than females(41.18%).The predominant age group was 45 to 64 years(20.78%).A total of 379 ADE signals were detected across 22 system-organ classes(SOC).The ADEs of dapagliflozin were mainly concentrated in the SOC such as infections and infestations,general disorders and administration sites conditions,and metabolism and nutrition disorders,aligning with information provided in the drug instructions.Additionally,the ADE signals were not documented in drug inserts such as scrotal gangrene,periperineal cellulitis,scrotal abscess,hyperglycemia,ketonuria,and pancreatitis.Conclusion When clinically using dapagliflozin,it is essential to conduct a thorough medication assessment.In addition to closely monitoring diabetes ketoacidosis,fungal infection,and acute renal injury.The latent ADEs that are not mentioned in the instructions to should be noticed ensure safe medication.

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