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.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.
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.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.
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.Mechanisms of Shexiang Baoxin Pill in homo-therapy for heteropathy in type 2 diabetes mellitus and coronary heart disease based on network pharmacology
Zifan ZHU ; Zhicong WANG ; Bin XIE ; Runhui LIU
Journal of Pharmaceutical Practice and Service 2024;42(4):173-180
Objective To probe into the mechanism of Shexiang Baoxin Pill in homo-therapy for heteropathy for type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD) based on network pharmacology. Methods All chemical components and action targets of these seven traditional Chinese medical in Shexiang Baoxin Pill were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Traditional Chinese Medicines Integrated Database (TCMID), The Encyclopedia of Traditional Chinese Medicine (ETCM) and BATMAN-TCM platform, and the DisGeNET and GeneCards databases were used to obtain CHD and T2DM-related Disease targets. The “drug-component-target” network map was constructed by Cytoscape 3.8.2 software, the protein-protein interaction (PPI) network map was constructed by STRING database, and the GO biological process analysis and KEGG pathway enrichment analysis were performed on the common targets of Shexiang Baoxin Pill for T2DM and CHD using DAVID online database. Results A total of 101 potential active ingredients for the treatment of T2DM and CHD in Shexiang Baoxin Pill were screened out, corresponding to 229 targets. Network analysis results showed that the common main active ingredients in Shexiang Baoxin Pill for treating T2DM and CHD might be chenodeoxycholic acid, ursodeoxycholic acid, cinnamic aldehyde, bile acids, cinnamic acid, and ginsenosides. The results of pathway enrichment analysis showed that the mechanism of action of Shexiang Baoxin Pill in the treatment of type 2 diabetes and coronary heart disease in treating T2DM and CHD might be related to the inhibition of inflammatory response and oxidative stress. Conclusion Shexiang Baoxin Pill could play a role in treating CHD and T2DM through multiple components, multiple targets and multiple pathways, which provided a certain theoretical basis for the clinical application and further research of Shexiang Baoxin Pill.
8.Predictive value of systemic immune-inflammation index and prognostic nutrition index in preterm infants with early-onset sepsis
Yubing PANG ; Zifan TONG ; Wenqiang LIU ; Yan XU ; Jun WANG
Chinese Pediatric Emergency Medicine 2024;31(5):327-332
Objective:To explore the predictive ability of systemic immune-inflammation index(SII)and prognostic nutrition index(PNI)for early-onset sepsis in preterm infants.Methods:Seventy preterm infants of 28 to 32 weeks,who were born in the Affiliated Hospital of Xuzhou Medical University from January 2019 to December 2022, and transferred to neonatal intensive care unit within 1 h conforming to EOS diagnostic criteria were selected as the EOS group,and 1∶1 matched non-infected preterm infants hospitalized during the same period were selected as control group.Relevant data were collected to compare the differences regarding clinical data,blood routine indicators,C-reactive protein(CRP),serum albumin levels(ALB),SII and PNI between two groups.The ability of SII and PNI to predict EOS was evaluated by Logistic regression analysis and receiver operating characteristic(ROC)curve.Results:Compared with control group,the EOS group had lower 1-minute and 5-minute Apgar scores,higher rates of cesarean section delivery and tracheal intubation,as well as higher rates of suppurative meningitis,bronchopulmonary dysplasia,retinopathy of prematurity and intracranial hemorrhage.The levels of blood routine parameters,ALB,SII and PNI in the EOS group were lower than those in control group,while CRP was increased.The differences were all statistically significant( P<0.05).Multivariate Logistic regression analysis showed that tracheal intubation,CRP,SII and PNI were independently influential factors of EOS( P<0.05).ROC curve analysis showed that the areas under curve of SII,PNI,CRP and SII combined with PNI were 0.808(95% CI 0.730-0.886),0.792(95% CI 0.718-0.865),0.633(95% CI 0.541-0.725)and 0.866(95% CI 0.803-0.929),the sensitivity were 74.3%,64.3%,42.9%,78.6%,and the specificity were 88.6%,82.9%,81.4%,90.0%,respectively.The cut-off values of SII,PNI and CRP were 221.36,38.65 and 0.80 mg/L,respectively. Conclusion:SII and PNI have a certain predictive value for EOS in preterm infants,and their combined diagnosis efficiency is more stronger.
9.Analysis of perioperative blood transfusion in patients with acute Stanford type A aortic dissection surgery
Shaoqiang ZHANG ; Qing LIU ; Zifan MENG ; Shuzhen LIU
Chinese Journal of Blood Transfusion 2024;37(9):1018-1022
【Objective】 To retrospectively analyze the blood transfusion of 322 patients with Stanford type A aortic coarctation in our hospital, and to explore the influencing factors of perioperative blood transfusion in patients and evaluate the effect. 【Methods】 The patients with Stanford A type aortic coarctation who underwent surgical treatment in our hospital from October 2020 to October 2023 were selected to analyze the differences in blood transfusion and the monitoring of blood routine and coagulation function between different surgical modalities, and to evaluate the influencing factors of massive blood transfusion. 【Results】 The intraoperative allogeneic red blood cell transfusion rate was 63.98% and the perioperative allogeneic red blood cell transfusion rate was 85.71% in patients with Stanford type A aortic coarctation. The intraoperative red blood cell, plasma, cryoprecipitates and platelet transfusion volumes for the Bentall procedure were (3.75±3.81) U, (608.13±314.77) mL, (15.25±8.39) U and (1.53±0.78) therapeutic doses, respectively, and had no difference compared with those for Sun′s procedure with the transfusion volume of (3.13±4.04) U, (707.61± 461.21) mL, (15.79±6.59) U and (1.54±0.64) therapeutic doses and those for Bentall&Sun’s procedure with the transfusion volume of (3.04±4.41) U, (813.48±582.02) mL, (18.39±6.43) U and (1.76±0.58) therapeutic doses(P>0.05). Preoperative hemoglobin levels were significantly lower in patients treated with Bentall procedure (127.75±23.17) g/L and in patients treated with Sun′s procedure (126.07±16.14) g/L than in patients treated with Bentall & Sun′s procedure(133.17±18.12) g/L(P<0.05). Postoperative hemoglobin, APTT and platelet counts were not statistically different between groups(P>0.05). Perioperative erythrocyte massive infusion accounted for 53.42%. The length of hospital days(days) in the massive transfusion group (23.83±9.74) was significantly higher than that in the conventional transfusion group (31.71±22.98), and the mortality rate in the massive infusion group 34.88% was significantly higher than that in the conventional transfusion group (5.33%)(P<0.05), and the hemoglobin level (g/L) at discharge in the massive infusion group(95.65±11.58)was lower than that in the conventional transfusion group(101.93±15.77)(P<0.05). 【Conclusion】 Blood transfusion is necessary to ensure the perioperative treatment of patients with acute Stanford type A aortic coarctation. Massive transfusion of red blood cells is accompanied by an increase in mortality rate and prolonged hospital stay. The test of coagulation function is helpful in guiding the use of blood components, and individualized restrictive transfusion strategy can reduce unnecessary blood transfusion and is conductive to patient safety.
10.Research progress in the effect of alternative splicing on radiosensitivity of cancer cells
Zifan QIN ; Xiaoli ZHENG ; Kangdong LIU ; Hong GE
Chinese Journal of Radiation Oncology 2024;33(5):479-484
Radiation therapy is one of the most important treatment methods for malignant tumors. Radiosensitivity is the key factor affecting the therapeutic effect of radiation therapy for tumor patients, which has been a hot topic of research. Alternative splicing is a vital post-transcriptional regulatory step in the process of gene expression. It can produce a variety of different splicing isoforms of pre-mRNA, and then produce various proteins which play a crucial role in maintaining normal life activities of the body. Compared with normal cells, tumor cells have a higher proportion of splicing disorder events, which can lead to the occurrence of pathological processes such as genomic instability and angiogenesis, thus resulting in the progression of diseases. Abnormal splicing events occurring in tumors can be used as new therapeutic targets. In this article, RNA alternative splicing, splicing events affecting radiosensitivity, and the prospects were reviewed.

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