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.Clinicopathological characteristics of SEMA5A and PD-L1 expression and correla-tion of the two genes in gastric cancer
Shilan PENG ; Zifan XU ; Jiarong YANG ; Sha LI ; Yuanyuan XU ; Guoqing PAN
Chinese Journal of Clinical and Experimental Pathology 2025;41(3):304-310,316
Purpose To investigate the expression of semaphorin 5 A(SEMA5A)and programmed death ligand-1(PD-L1)and their clinicopathological significance in gastric cancer.Methods Clinical data of 41 cases of gastric cancer tissues and paired adjacent tissues were collected.Immunohistochemical staining and RT-qPCR were used to de-tect the expression levels of SEMA5A and PD-L1,and analysed the correlation between SEMA5A and PD-L1 and clini-copathological features.In addition,we used lentivirus to construct SEMA5A stable low-expression cell lines.RT-qPCR and Western blot were used to analyse the correlation between the expression of SEMA5A and PD-L1 in gastric cancer tissues.Results The high expression rate of SEMA5A was 65.9%(27/41)in gastric cancer tissues and 39.0%(16/41)in paracancerous tissues,respectively.The positive rates of PD-L1 were 58.5%(24/41)and 14.6%(6/41),respectively.RT-qPCR showed that the relative expression levels of SEMA5A mRNA in gastric cancer and paracancerous tissues were 1.30±0.50 and 0.81±0.48,respectively,while the relative expression levels of PD-L1 mRNA were 0.70±0.42 and 0.12±0.09,respectively.SEMA5A expression was correlated with histological typ-ing of gastric cancer and lymph node metastasis(P<0.05).PD-L1 expression was correlated with tumour size,T stage,and pathological stage of gastric cancer(P<0.05).Pearson correlation analysis showed a positive correlation between the expression of SEMA5A and PD-L1 mRNA in gastric cancer tissues,and spearman correlation analysis showed that there was no correlation between the expression of the two in paracancerous tissues.Knockdown of SE-MA5A gene in human gastric adenocarcinoma cell lines resulted in down-regulation of PD-L1 expression.Conclusion Both SEMA5A and PD-L1 are highly expressed in gastric cancer tissues,and there is a correlation between the ex-pressions of SEMA5A and PD-L1.They can serve as potential molecular markers for prognostic evaluation and combi-nation therapy of gastric cancer.
3.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.
4.Neonatal alloimmune thrombocytopenia complicated with piperacillin drug antibody: a case report
Zifan MENG ; Shaoqiang ZHANG ; Qiang JU ; Ying LI ; Songxia YAN ; Haiyan WANG
Chinese Journal of Blood Transfusion 2025;38(7):969-974
Objective: To investigate the clinical symptoms, laboratory tests, and treatment strategies of a case of fetal/neonatal alloimmune thrombocytopenia (FNAIT) complicated with piperacillin drug antibody. Methods: The platelet antibodies in the mother were screened and identified by ELISA. The HLA antigens of the newborn were genotyped through PCR-SSO, while the specificity of HLA antibodies in the mother was determined using a Single Antigen kit. The drug antibody was detected by a piperacillin kit. Results: Maternal antibodies against paternally-derived platelet antigens were detected. The HLA genotypes of the newborn were identified as HLA A
33∶03 and HLA B
58∶01. The mother exhibited strong positive antibodies against the specific platelet antigens of the newborn, namely anti-HLA-A33 and anti-HLA-B58 antibodies. The piperacillin antibody was detected in the newborn. Following treatment of continuous intravenous immunoglobulin (IVIG), platelet transfusions, red blood cell transfusions and discontinuation of piperacillin treatment, the platelet count and hemoglobin levels increased in the newborn. Conclusion: The newborn in this case was diagnosed with FNAIT complicated by the presence of anti-HLA-A33 and anti-HLA-B58 antibodies, as well as drug-induced hemolytic anemia caused by piperacillin drug antibody. The condition is more complicated under the influence of dual immune antibodies. Laboratory detection techniques such as platelet antibody and drug antibody tests can assist in early clinical diagnosis. At the same time, more active drug and blood transfusion treatments should be given in clinical practice to improve the prognosis.
5.Neonatal alloimmune thrombocytopenia complicated with piperacillin drug antibody: a case report
Zifan MENG ; Shaoqiang ZHANG ; Qiang JU ; Ying LI ; Songxia YAN ; Haiyan WANG
Chinese Journal of Blood Transfusion 2025;38(7):969-974
Objective: To investigate the clinical symptoms, laboratory tests, and treatment strategies of a case of fetal/neonatal alloimmune thrombocytopenia (FNAIT) complicated with piperacillin drug antibody. Methods: The platelet antibodies in the mother were screened and identified by ELISA. The HLA antigens of the newborn were genotyped through PCR-SSO, while the specificity of HLA antibodies in the mother was determined using a Single Antigen kit. The drug antibody was detected by a piperacillin kit. Results: Maternal antibodies against paternally-derived platelet antigens were detected. The HLA genotypes of the newborn were identified as HLA A
33∶03 and HLA B
58∶01. The mother exhibited strong positive antibodies against the specific platelet antigens of the newborn, namely anti-HLA-A33 and anti-HLA-B58 antibodies. The piperacillin antibody was detected in the newborn. Following treatment of continuous intravenous immunoglobulin (IVIG), platelet transfusions, red blood cell transfusions and discontinuation of piperacillin treatment, the platelet count and hemoglobin levels increased in the newborn. Conclusion: The newborn in this case was diagnosed with FNAIT complicated by the presence of anti-HLA-A33 and anti-HLA-B58 antibodies, as well as drug-induced hemolytic anemia caused by piperacillin drug antibody. The condition is more complicated under the influence of dual immune antibodies. Laboratory detection techniques such as platelet antibody and drug antibody tests can assist in early clinical diagnosis. At the same time, more active drug and blood transfusion treatments should be given in clinical practice to improve the prognosis.
6.The significance and advancements of circulating tumor DNA in the diagnosis and treatment of operable non-small cell lung cancer
Zifan LI ; Yue HE ; Kezhong CHEN
Chinese Journal of Surgery 2025;63(2):171-176
Non-small cell lung cancer, characterized by high incidence and mortality rates, significantly threatens human health. Precisely assessing patient prognosis and implementing adaptive treatment strategies have emerged as pivotal issues in contemporary thoracic oncology. Postoperative minimal residual disease (MRD) detection through liquid biopsy has demonstrated substantial potential. Circulating tumor DNA (ctDNA) enables real-time dynamic monitoring of tumor alterations. With advancements in ctDNA detection technologies, ctDNA has become a core method for MRD assessment. In the context of postoperative surveillance, ctDNA detection facilitates more accurate prognostic stratification and early prediction of tumor recurrence. Regarding therapeutic interventions, ctDNA detection can predict the efficacy of neoadjuvant and adjuvant therapies. In the future, further elucidating the value of assessing ctDNA status in predicting patient prognosis and guiding drug therapies will contribute to the advancement of precision medicine and adaptive treatments.
7.Clinicopathological characteristics of SEMA5A and PD-L1 expression and correla-tion of the two genes in gastric cancer
Shilan PENG ; Zifan XU ; Jiarong YANG ; Sha LI ; Yuanyuan XU ; Guoqing PAN
Chinese Journal of Clinical and Experimental Pathology 2025;41(3):304-310,316
Purpose To investigate the expression of semaphorin 5 A(SEMA5A)and programmed death ligand-1(PD-L1)and their clinicopathological significance in gastric cancer.Methods Clinical data of 41 cases of gastric cancer tissues and paired adjacent tissues were collected.Immunohistochemical staining and RT-qPCR were used to de-tect the expression levels of SEMA5A and PD-L1,and analysed the correlation between SEMA5A and PD-L1 and clini-copathological features.In addition,we used lentivirus to construct SEMA5A stable low-expression cell lines.RT-qPCR and Western blot were used to analyse the correlation between the expression of SEMA5A and PD-L1 in gastric cancer tissues.Results The high expression rate of SEMA5A was 65.9%(27/41)in gastric cancer tissues and 39.0%(16/41)in paracancerous tissues,respectively.The positive rates of PD-L1 were 58.5%(24/41)and 14.6%(6/41),respectively.RT-qPCR showed that the relative expression levels of SEMA5A mRNA in gastric cancer and paracancerous tissues were 1.30±0.50 and 0.81±0.48,respectively,while the relative expression levels of PD-L1 mRNA were 0.70±0.42 and 0.12±0.09,respectively.SEMA5A expression was correlated with histological typ-ing of gastric cancer and lymph node metastasis(P<0.05).PD-L1 expression was correlated with tumour size,T stage,and pathological stage of gastric cancer(P<0.05).Pearson correlation analysis showed a positive correlation between the expression of SEMA5A and PD-L1 mRNA in gastric cancer tissues,and spearman correlation analysis showed that there was no correlation between the expression of the two in paracancerous tissues.Knockdown of SE-MA5A gene in human gastric adenocarcinoma cell lines resulted in down-regulation of PD-L1 expression.Conclusion Both SEMA5A and PD-L1 are highly expressed in gastric cancer tissues,and there is a correlation between the ex-pressions of SEMA5A and PD-L1.They can serve as potential molecular markers for prognostic evaluation and combi-nation therapy of gastric cancer.
8.The significance and advancements of circulating tumor DNA in the diagnosis and treatment of operable non-small cell lung cancer
Zifan LI ; Yue HE ; Kezhong CHEN
Chinese Journal of Surgery 2025;63(2):171-176
Non-small cell lung cancer, characterized by high incidence and mortality rates, significantly threatens human health. Precisely assessing patient prognosis and implementing adaptive treatment strategies have emerged as pivotal issues in contemporary thoracic oncology. Postoperative minimal residual disease (MRD) detection through liquid biopsy has demonstrated substantial potential. Circulating tumor DNA (ctDNA) enables real-time dynamic monitoring of tumor alterations. With advancements in ctDNA detection technologies, ctDNA has become a core method for MRD assessment. In the context of postoperative surveillance, ctDNA detection facilitates more accurate prognostic stratification and early prediction of tumor recurrence. Regarding therapeutic interventions, ctDNA detection can predict the efficacy of neoadjuvant and adjuvant therapies. In the future, further elucidating the value of assessing ctDNA status in predicting patient prognosis and guiding drug therapies will contribute to the advancement of precision medicine and adaptive treatments.
9.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.
10.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.

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