1.Development and clinical application of a machine learning-driven model for metabolite-based diagnosis of small cell lung cancer
Xin HUANG ; Jiahui LIU ; Jingwen YE ; Wenli QIAN ; Wanxing XU ; Lin WANG
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(8):1009-1016
Objective·To develop an early diagnostic model for small cell lung cancer(SCLC)based on differences in serum metabolite expression profiles between patients with SCLC and those with benign pulmonary diseases,using machine learning algorithms.Methods·Serum samples were collected from 29 SCLC patients and 67 patients with benign lung diseases at Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,as the training cohort.An independent external validation cohort included 20 SCLC patients and 40 patients with benign lung diseases from Gansu Provincial Cancer Hospital.A total of 69 serum metabolites were quantitatively analyzed using liquid chromatography-tandem mass spectrometry(LC-MS/MS).The XGBoost Classifier was employed to rank metabolite importance,and a forward feature selection strategy based on XGBoost was used to identify a subset of key metabolites.Diagnostic models were constructed using AdaBoost,random forest(RF),and light gradient boosting machine(LGBM)algorithms.Model performance was assessed using receiver operating characteristic(ROC)curves and the area under the curve(AUC),and validated on the external test cohort.Results·Principal component analysis(PCA)and orthogonal projections to latent structures-discriminant analysis(OPLS-DA)of the training cohort revealed distinct metabolic profiles between SCLC and benign lung disease patients.Based on feature importance rankings,six key metabolites were selected to construct the MTB-6 diagnostic model.Among the models,AdaBoost achieved the best performance,with an AUC of 0.943,sensitivity of 75.0%,and specificity of 90.9%in the training cohort.In the external test cohort,the model demonstrated robust performance with an AUC of 0.921,sensitivity of 80.0%,and specificity of 87.5%.Conclusion·The MTB-6 model,based on six serum metabolites and the AdaBoost algorithm,exhibits excellent diagnostic performance and holds potential for the differential diagnosis of SCLC and benign pulmonary diseases.
2.Selection and research advances of intraperitoneal drug treatment for colorectal peritoneal metastasis
Xiaoyan HUANG ; Jingwen XIE ; Xiusen QIN ; Yuanxin ZHANG ; Rui LUO ; Huabin HU ; Junwen YE ; Huaiming WANG ; Lili CHU ; Rongkang HUANG ; Hui WANG ; Xiaoyan LI
Chinese Journal of Gastrointestinal Surgery 2025;28(5):564-573
Peritoneal metastasis is a common form of distant metastasis in patients with colorectal cancer, and it is typically associated with a poor prognosis. The development of peritoneal metastasis involves complex molecular mechanisms and multifactorial regulation of the tumor microenvironment. Due to the presence of the blood-peritoneal barrier, only a small amount of systemic medication reaches the peritoneal cavity, resulting in limited efficacy against peritoneal metastasis. Intraperitoneal administration shows significant therapeutic advantages as it can directly target the tumor microenvironment, maintain high local drug concentrations, and reduce systemic toxicity. Intraperitoneal chemotherapy, especially hyperthermic intraperitoneal chemotherapy, has become a cornerstone therapeutic strategy in the clinical treatment of peritoneal metastasis. When selecting chemotherapy drugs and drug combinations, pharmacokinetic properties, efficacy, and safety must be comprehensively considered to optimize the treatment outcomes. In addition, the unique microenvironment of the peritoneal cavity provides new treatment approaches for biological treatment strategies, including antitoxins, vaccines, immune checkpoint inhibitors, etc. Techniques such as pressurized intraperitoneal aerosol chemotherapy and novel drug delivery systems demonstrate potential for enhanced efficacy, offering promising alternatives to improve patient outcomes. This article will review peritoneal barrier characteristics, intraperitoneal drug transport, intraperitoneal chemotherapy, and intraperitoneal biological therapies, thereby establishing a theoretical framework for precision therapy in colorectal cancer peritoneal metastasis.
3.GSTP1-mediated inhibition of ACSL4-dependent ferroptosis via JNK pathway in DOX-induced cardiomyopathy.
Mingbo WU ; Ye ZHAO ; Dong LI ; Xueli HU ; Jiaojiao ZHOU ; Siyi CHEN ; Xin YANG ; Zegang LI ; Xiaomiao RUAN ; Jingwen YANG ; Wenwu LING
Chinese Medical Journal 2025;138(19):2498-2510
BACKGROUND:
Doxorubicin hydrochloride (DOX) is extensively used in the treatment of various tumors. However, its clinical application is limited due to dose-dependent cardiotoxicity. Currently, few effective strategies exist to mitigate or eliminate DOX-induced cardiomyopathy (DIC). Although ferroptosis is implicated in DIC and its inhibition partially alleviates the condition, the direct targets of DOX in the progression of cardiotoxicity remain unclear. This study aimed to discover the direct targets of DOX in ferroptosis-mediated DIC.
METHODS:
A DOX pulldown assay was performed to identify proteins specifically binding to DOX in murine hearts, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify candidate proteins. A cardiac injury mouse model was established by DOX treatment. Based on this, multiple ferroptosis biomarkers were detected by flow cytometry, quantitative real-time polymerase chain reaction, western blotting, immunochemistry, etc. Besides, specific activator and inhibitor of signaling pathways were applied to illuminate molecular mechanisms.
RESULTS:
Glutathione S-transferase P1 (GSTP1) was identified as a DOX target. GSTP1 activity was inhibited in DOX-treated cardiomyocytes, while its overexpression significantly alleviated DIC. Moreover, GSTP1 overexpression inhibited acyl-CoA synthetase long-chain family member 4 (ACSL4)-dependent ferroptosis. Mechanistically, GSTP1 overexpression suppressed c-Jun N-terminal kinase (JNK) phosphorylation, thereby reducing reactive oxygen species (ROS) production and inhibiting ferroptosis in DIC.
CONCLUSIONS
This study identifies the DOX/GSTP1/JNK axis as a critical pathway mediating ACSL4-dependent ferroptosis in DIC. GSTP1 is highlighted as a potential key mediator of ferroptosis and a promising therapeutic target for DIC.
4.Development and clinical application of a machine learning-driven model for metabolite-based diagnosis of small cell lung cancer
Xin HUANG ; Jiahui LIU ; Jingwen YE ; Wenli QIAN ; Wanxing XU ; Lin WANG
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(8):1009-1016
Objective·To develop an early diagnostic model for small cell lung cancer(SCLC)based on differences in serum metabolite expression profiles between patients with SCLC and those with benign pulmonary diseases,using machine learning algorithms.Methods·Serum samples were collected from 29 SCLC patients and 67 patients with benign lung diseases at Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,as the training cohort.An independent external validation cohort included 20 SCLC patients and 40 patients with benign lung diseases from Gansu Provincial Cancer Hospital.A total of 69 serum metabolites were quantitatively analyzed using liquid chromatography-tandem mass spectrometry(LC-MS/MS).The XGBoost Classifier was employed to rank metabolite importance,and a forward feature selection strategy based on XGBoost was used to identify a subset of key metabolites.Diagnostic models were constructed using AdaBoost,random forest(RF),and light gradient boosting machine(LGBM)algorithms.Model performance was assessed using receiver operating characteristic(ROC)curves and the area under the curve(AUC),and validated on the external test cohort.Results·Principal component analysis(PCA)and orthogonal projections to latent structures-discriminant analysis(OPLS-DA)of the training cohort revealed distinct metabolic profiles between SCLC and benign lung disease patients.Based on feature importance rankings,six key metabolites were selected to construct the MTB-6 diagnostic model.Among the models,AdaBoost achieved the best performance,with an AUC of 0.943,sensitivity of 75.0%,and specificity of 90.9%in the training cohort.In the external test cohort,the model demonstrated robust performance with an AUC of 0.921,sensitivity of 80.0%,and specificity of 87.5%.Conclusion·The MTB-6 model,based on six serum metabolites and the AdaBoost algorithm,exhibits excellent diagnostic performance and holds potential for the differential diagnosis of SCLC and benign pulmonary diseases.
5.Selection and research advances of intraperitoneal drug treatment for colorectal peritoneal metastasis
Xiaoyan HUANG ; Jingwen XIE ; Xiusen QIN ; Yuanxin ZHANG ; Rui LUO ; Huabin HU ; Junwen YE ; Huaiming WANG ; Lili CHU ; Rongkang HUANG ; Hui WANG ; Xiaoyan LI
Chinese Journal of Gastrointestinal Surgery 2025;28(5):564-573
Peritoneal metastasis is a common form of distant metastasis in patients with colorectal cancer, and it is typically associated with a poor prognosis. The development of peritoneal metastasis involves complex molecular mechanisms and multifactorial regulation of the tumor microenvironment. Due to the presence of the blood-peritoneal barrier, only a small amount of systemic medication reaches the peritoneal cavity, resulting in limited efficacy against peritoneal metastasis. Intraperitoneal administration shows significant therapeutic advantages as it can directly target the tumor microenvironment, maintain high local drug concentrations, and reduce systemic toxicity. Intraperitoneal chemotherapy, especially hyperthermic intraperitoneal chemotherapy, has become a cornerstone therapeutic strategy in the clinical treatment of peritoneal metastasis. When selecting chemotherapy drugs and drug combinations, pharmacokinetic properties, efficacy, and safety must be comprehensively considered to optimize the treatment outcomes. In addition, the unique microenvironment of the peritoneal cavity provides new treatment approaches for biological treatment strategies, including antitoxins, vaccines, immune checkpoint inhibitors, etc. Techniques such as pressurized intraperitoneal aerosol chemotherapy and novel drug delivery systems demonstrate potential for enhanced efficacy, offering promising alternatives to improve patient outcomes. This article will review peritoneal barrier characteristics, intraperitoneal drug transport, intraperitoneal chemotherapy, and intraperitoneal biological therapies, thereby establishing a theoretical framework for precision therapy in colorectal cancer peritoneal metastasis.
6.Construction and Application of Decision Support System for Learning Experience of TCM Master Zhou Zhongying in Diag-nosing and Treating Major Chronic Diseases
Jingwen ZHOU ; Liu LI ; Fang YE
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(12):1303-1307
Based on the research on the inheritance of clinical experience of traditional Chinese medicine(TCM)master Zhou Zhongying in the diagnosis and treatment of major chronic diseases,a decision support system for learning experience of Zhou Zhongy-ing in diagnosing and treating major chronic diseases was constructed based on intelligent technology.First,the outpatient paper medi-cal records kept by Professor Zhou Zhongying since the 1980s were digitized.Then,data mining was performed on the electronic data-base to form a structured database and knowledge element module network.Finally,the mined results were used to interview famous doctors.The promotion and application of this system in clinical practice has realized a new method of original inheritance and learning of the experience of Zhou Zhongying in diagnosing and treating major chronic diseases.It has greatly improved the diagnosis and treat-ment ideas of middle-aged and young Chinese medicine practitioners in dealing with personalized,complex and changeable major chro-nic diseases,breaking through the traditional one-to-one teaching model of"master-apprentice",and forming a new model of large-scale TCM inheritance education.
7.Construction and Application of Decision Support System for Learning Experience of TCM Master Zhou Zhongying in Diag-nosing and Treating Major Chronic Diseases
Jingwen ZHOU ; Liu LI ; Fang YE
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(12):1303-1307
Based on the research on the inheritance of clinical experience of traditional Chinese medicine(TCM)master Zhou Zhongying in the diagnosis and treatment of major chronic diseases,a decision support system for learning experience of Zhou Zhongy-ing in diagnosing and treating major chronic diseases was constructed based on intelligent technology.First,the outpatient paper medi-cal records kept by Professor Zhou Zhongying since the 1980s were digitized.Then,data mining was performed on the electronic data-base to form a structured database and knowledge element module network.Finally,the mined results were used to interview famous doctors.The promotion and application of this system in clinical practice has realized a new method of original inheritance and learning of the experience of Zhou Zhongying in diagnosing and treating major chronic diseases.It has greatly improved the diagnosis and treat-ment ideas of middle-aged and young Chinese medicine practitioners in dealing with personalized,complex and changeable major chro-nic diseases,breaking through the traditional one-to-one teaching model of"master-apprentice",and forming a new model of large-scale TCM inheritance education.
8.A case report of severe hematuria after transrectal prostate biopsy treated by repeat interventional embolization
Jingwen REN ; Ye TIAN ; Guangheng LUO
Chinese Journal of Urology 2023;44(5):390-391
Hemorrhage after prostate biopsy is common, but hemorrhagic shock is rare. We reported a case of sudden severe hematuria on the third day after prostate biopsy, which was considered to be bleeding at the puncture site. Conservative treatment was ineffective, and interventional embolization was performed. Bilateral bulbar urethral arteries were embolized, and the bleeding was stopped successfully. On the 4th day after embolization, the patient developed hypovolemic shock. Angiography showed bilateral prostatic artery bleeding, and the bleeding site and its superior branch arteries were embolized immediately. At 4 months after embolization, no bleeding related events occurred.
9.Effect of 5 methods of critical illness score in the prognosis evaluation of sepsis-associated encephalopathy
Yihao CHEN ; Yuxiong GUO ; Xufeng LI ; Xiaoting YE ; Jingwen ZHANG ; Chun WANG ; Yan HU ; Jing WANG ; Jiaxing WU ; Guilang ZHENG ; Yueyu SUN ; Yiyu DENG ; Yiyun LU
Chinese Journal of Emergency Medicine 2022;31(4):520-527
Objective:To explore the effect of pediatric critical illness score (PCIS), pediatric risk of mortality Ⅲ score (PRISM Ⅲ), pediatric logistic organ dysfunction 2 (PELOD-2), pediatric sequential organ failure assessment (p-SOFA) score and Glasglow coma scale (GCS) in the prognosis evaluation of septic-associated encephalopathy (SAE).Methods:The data of children with SAE admitted to the Pediatric Intensive Care Unit (PICU), Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences from January 2010 to December 2020 were retrospectively analyzed. They were divided into the survival and death groups according to the clinical outcome on the 28th day after admission. The efficiency of PCIS, PRISM Ⅲ, PELOD-2, p-SOFA and GCS scores for predicting death were evaluated by the area under the ROC curve (AUC). The Hosmer-Lemeshow goodness-of-fit test assessed the calibration of each scoring system.Results:Up to 28 d after admission, 72 of 82 children with SAE survived and 10 died, with a mortality rate of 12.20%. Compared with the survival group, the death group had significantly lower GCS [7 (3, 12) vs. 12 (8, 14)] and PCIS scores [76 (64, 82) vs. 82 (78, 88)], and significantly higher PRISM Ⅲ [14 (12, 17) vs. 7 (3, 12)], PELOD-2 [8 (5, 13) vs. 4 (2, 7)] and p-SOFA scores [11 (5, 12) vs. 6 (3, 9)] ( P<0.05). The AUCs of PCIS, PRISM Ⅲ, PELOD-2, p-SOFA and GCS scores for predicting SAE prognosis were 0.773 ( P=0.012, AUC>0.7), 0.832 ( P=0.02, AUC>0.7), 0.767 ( P=0.014, AUC>0.7), 0.688 ( P=0.084, AUC<0.7), and 0.692 ( P=0.077,AUC<0.7), respectively. Hosmer-Lemeshow goodness-of-fit test showed that PCIS ( χ2=5.329, P=0.722) predicted the mortality and the actual mortality in the best fitting effect, while PRISM Ⅲ ( χ2=12.877, P=0.177), PELOD-2 ( χ2=8.487, P=0.205), p-SOFA ( χ2=9.048, P=0.338) and GCS ( χ2=3.780, P=0.848) had poor fitting effect. Conclusions:The PCIS, PRISM Ⅲ and PELOD-2 scores have good predictive ability assessing the prognosis of children with SAE, while the PCIS score can more accurately evaluate the fitting effect of SAE prognosis prediction.
10.The preference for Front-of-Pack Labeling and its association with the understanding of Nutrition Facts Panel among residents aged 18 to 70: results of a survey in 6 provinces of China
Yiluan HU ; Ruijie YAN ; Yan JIANG ; Jingwen ZHANG ; Lihong YE ; Lin XIANG ; Jia CUI ; Yuxiang TANG ; Chao GAO ; Li XIAO ; Yuexin YANG ; Juan ZHANG
Chinese Journal of Preventive Medicine 2022;56(7):952-959
Objective:To investigate the preference for Front-of-Pack Labeling (FOP) and its association with the understanding of the Nutrition Facts Panel among Chinese residents.Methods:A multi-stage sampling strategy was adopted to select 3 002 people aged between 18 and 70 years old from the eastern region of China (Beijing, Jiangsu Province, Guangdong Province), the northeast region (Heilongjiang Province), the central region (Henan Province) and the western region (Sichuan Province) from July 2020 to March 2021. Socio-demographic characteristics of participants and their understanding of the Nutrition Facts Panel and preference for FOP were collected. The χ2 test was conducted to compare the preference for FOP in different groups of population, and multivariate logistic regression was used to analyze the association between the preference for FOP and the understanding of the Nutrition Facts Panel. Results:The mean age of 3 002 participants was (42.3±13.4) years, of which 1 914 (63.8%) were females and 69.3% could not understand the Nutrition Facts Panel. About 2 458 respondents (81.9%) suggested that FOP could be promoted. The top three nutrients that should be labeled were sugar (68.4%), salt (68.2%) and total fat (62.4%). The number of participants who believed that the Multiple Traffic Lights (MTL) could be easier to help consumers to quickly choose healthy food, attract attention and provide the most needed information was 1 064 (35.4%), 1 026 (34.2%) and 1 140 (38.0%), respectively. The multivariate logistic regression analysis showed that, compared with the Guideline Daily Amount (GDA) system, participants who could not understand the Nutrition Facts Panel preferred (1) Nutri-Score, Warning labels, and Health logos: Smart Choice in terms of"Which format of FOP could quickly help you choose food more easily?"[ OR (95% CI): 2.21 (1.62-3.02), 1.64 (1.22-2.22), 1.79 (1.31-2.45), respectively]; (2) Nutri-Score, Warning labels, and Health logos: Smart Choice in terms of"Which format of FOP could attract your attention the most?"[ OR (95% CI): 2.62 (1.92-3.59), 1.96 (1.45-2.66), 2.25 (1.66-3.04), respectively]; and (3) Nutri-Score, Warning labels, and Health logos: Smart Choice in terms of"Which format of FOP could provide you with the most needed information?"[ OR (95% CI): 2.33 (1.70-3.21), 2.21 (1.66-2.95), 2.01 (1.50-2.71), respectively]. Conclusion:The residents from six provinces in China have a supportive attitude towards FOP. The interpretive FOP with color information, specific nutrient information and summary indicator can be launched. The nutrition information of sugar, salt and total fat could be prioritized to be labeled on the FOP.

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