1.Explainable Machine Learning Model for Predicting Prognosis in Patients with Malignant Tumors Complicated by Acute Respiratory Failure: Based on the eICU Collaborative Research Database in the United States
Zihan NAN ; Linan HAN ; Suwei LI ; Ziyi ZHU ; Qinqin ZHU ; Yan DUAN ; Xiaoting WANG ; Lixia LIU
Medical Journal of Peking Union Medical College Hospital 2026;17(1):98-108
To develop and validate a model for predicting intensive care unit (ICU) mortality risk in patients with malignant tumors complicated by acute respiratory failure (ARF) based on an explainable machine learning framework. Clinical data of patients with malignant tumors and ARF were extracted from the eICU Collaborative Research Database in the United States, including demographic characteristics, comorbidities, vital signs, laboratory test indicators, and major interventions within the first 24 hours after ICU admission.The study outcome was ICU death.Enrolled patients were randomly divided into a training set and a validation set at a ratio of 7:3.Predictor variables were selected using least absolute shrinkage and selection operator (LASSO) regression.Five machine learning algorithms-extreme gradient boosting (XGBoost), support vector machine (SVM), Logistic regression, multilayer perceptron (MLP), and C5.0 Decision Tree-were employed to construct predictive models.Model performance was evaluated based on the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and other metrics.The optimal model was further interpreted using the Shapley additive explanations (SHAP) algorithm. A total of 3196 patients with malignant tumors complicated by ARF were included.The training set comprised 2, 261 patients and the validation set 935 patients; 683 patients died during ICU stay, while 2513 survived.LASSO regression ultimately selected 12 variables closely associated with patient ICU outcomes, including sepsis comorbidity, use of vasoactive drugs, and within the first 24 hours after ICU admission: minimum mean arterial pressure, maximum heart rate, maximum respiratory rate, minimum oxygen saturation, minimum serum bicarbonate, minimum blood urea nitrogen, maximum white blood cell count, maximum mean corpuscular volume, maximum serum potassium, and maximum blood glucose.After model evaluation, the XGBoost model demonstrated the best performance.The AUCs for predicting ICU mortality risk in the training and validation sets were 0.940 and 0.763, respectively; accuracy was 88.3% and 81.2%;sensitivity was 98.5% and 95.9%.Its predictive performance also remained optimal in sensitivity analyses.SHAP analysis indicated that the top five variables contributing to the model's predictions were minimum oxygen saturation, minimum serum bicarbonate, minimum mean arterial pressure, use of vasoactive drugs, and maximum white blood cell count. This study successfully developed a mortality risk prediction model for ICU patients with malignant tumors complicated by ARF based on a large-scale dataset and performed explainability analysis.The model aids clinicians in early identification of high-risk patients and implementing individualized interventions.
2.LINC00657 Promotes Malignant Progression of Cervical Cancer by Sponging miR-30a-5p to Regulate Skp2 Expression
Changhui ZHOU ; Jingqin REN ; Zhen CHEN ; Qi YAN ; Nan YANG ; Jiaqi ZHAO ; Rong LI
Cancer Research on Prevention and Treatment 2026;53(2):103-111
Objective To investigate the role and regulatory mechanism of LINC00657 in the progression of cervical cancer. Methods Bioinformatics analysis predicted potential binding sites between LINC00657 and miR-30a-5p and between miR-30a-5p and Skp2. These sites were verified by using RNA immunoprecipitation and dual-luciferase reporter experiments. LINC00657, miR-30a-5p, and Skp2 mRNA expression levels in cervical cancer tissues and cell lines were assessed by utilizing RT-qPCR. Western blot analysis was employed to examine the protein levels of Skp2 in cells and subcutaneous xenograft tumor models in nude mice. Immunohistochemistry was applied to analyze Skp2 expression in animal tissues. The cellular processes of cervical cancer cell lines were evaluated through CCK-8, scratch, and Transwell assays. Results LINC00657 and Skp2 presented binding sites for miR-30a-5p. In cervical cancer, LINC00657 and Skp2 showed high expression levels (P<0.05), whereas miR-30a-5p displayed low expression (P<0.05). Functional experiments demonstrated that linc00657 upregulates Skp2 expression, a process that is dependent on its sequestration of miR-30a-5p. Conclusion LINC00657 promoted the malignant progression of cervical cancer by upregulating Skp2 expression through specifically sequestering miR-30a-5p, thereby relieving its inhibitory effect on the target gene Skp2.
3.UPLC-Q-TOF-MS Reveals Mechanisms of Modified Qing'e Formula in Delaying Skin Photoaging and Regulating Circadian Rhythm
Wanyu YANG ; Xiujun ZHANG ; Yan WANG ; Chunjing SONG ; Haoming MA ; Lifeng WANG ; Nan LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):88-97
ObjectiveTo reveal the active substances and mechanisms of modified Qing'e formula (MQEF) in delaying skin photoaging by ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF-MS),network pharmacology, and cell experiments. MethodsUPLC-Q-TOF-MS and a literature review were employed to analyze the transdermally absorbed components in mice after the topical application of MQEF. The potential targets of MQEF in treating skin photoaging were retrieved from databases.The compound-potential target network and protein-protein interaction network were constructed to screen the key components and core targets. A photoaging cell model was established by irradiating HaCaT cells with medium-wave ultraviolet B (UVB). The safe doses of bakuchiol (BAK) and salvianolic acid B (SAB) for treating HaCaT cells and the effects of BAK and SAB on the viability of cells exposed to UVB irradiation were determined by the cell counting kit-8 (CCK-8) method.The reactive oxygen species (ROS) fluorescent probe was used to measure the ROS production in the cells treated with BAK and SAB.The expression levels of genes related to oxidative stress,inflammation,collagen metabolism,and circadian rhythm clock were measured by Real-time PCR. ResultsA total of 24 transdermally absorbed components of MQEF were identified,which acted on 367 potential targets,and 417 targets related to skin photoaging were screened out,among which 47 common targets were predicted as the targets of MQEF in treating skin photoaging. MQEF exerted the anti-photoaging effect via key components such as BAK and SAB,which acted on core proteins such as serine/threonine kinase 1 (Akt1) and mitogen-activated protein kinase 3 (MAPK3) and intervened in core pathways such as the tumor necrosis factor (TNF) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathways.Compared with the model group,the administration of BAK and SAB increased the survival rate of HaCaT cells (P<0.01),down-regulated the mRNA levels of cyclooxygenase-2 (COX-2),interleukin-6 (IL-6),tumor necrosis factor-α (TNF-α),matrix metalloproteinase-1 (MMP-1),and matrix metalloproteinase-9 (MMP-9) (P<0.01),and up-regulated the mRNA levels of heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO-1) (P<0.05,P<0.01) in photoaged HaCaT cells.In addition,it eliminated excess ROS production induced by UVB and up-regulated the mRNA levels of brain and muscle ARNT-like 1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK) associated with circadian clock (P<0.05,P<0.01). ConclusionMQEF delays skin photoaging through the coordinated effects of various components,multiple targets,and diverse pathways.The key components BAK and SAB in MQEF exhibit anti-photoaging properties,which involve inhibiting oxidative stress,preventing collagen degradation,mitigating inflammation,and maintaining normal skin circadian rhythms by regulating clock gene expression.
4.Mechanisms of reproductive toxicity and ferroptosis induced by polystyrene microplastics in male mice
Jiabo WANG ; Rong LI ; Setiniaz NAZIRA ; Chengqing LIU ; Nan YANG ; Qi YAN
Journal of Environmental and Occupational Medicine 2025;42(2):224-231
Background Polystyrene microplastics (PS-MPs) attract widespread public attention due to their adverse effects on mammalian reproductive systems. However, it is currently unclear whether ferroptosis is related to testicular damage and decreased sperm quality in mice exposed to PS-MPs. Objective To clarify the reproductive damage in male mice exposed to PS-MPs and investigate the mechanism of ferroptotic effects. Methods Five-week-old male BALB/c mice were randomly divided into four experimental groups, including one control group and three PS-MPs groups at low dose (0.5 mg·kg−1), medium dose (5 mg·kg−1), and high dose (50 mg·kg−1), respectively, with 6 mice in each group. The treatment was delivered by gavage for 35 consecutive days (one time per day). After the mice were neutralized, the wet weights of testis and epididymis were measured, and organ coefficients were then calculated. Sperm was counted by hematimetry, and sperm motility and adenosine triphosphate (ATP) level were evaluated using CCK-8 and CellTiter Glo ® Kit 2.0 Assay respectively. In addition, serum testosterone, follicle-stimulating hormone, and luteinizing hormone were determined using ELISA kit, total testicular iron content was measured using tissue iron kit, and pathological changes in testicular tissue were observed after hematoxylin-eosin (HE) staining. We also used glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD) assays to examine their changes to better understand the physiological status of testicular tissue. Finally, the expression levels of ferroptosis-associated proteins glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) were detected by Western blotting. Results Compared with the control group, the testicular index in the high dose group decreased, and the epididymal index decreased in all dose groups (P<0.05). The results of sperm quality analysis showed that the sperm count in each dose group was lower than that of the control group; the sperm motility decreased, sperm malformation rate increased, and ATP level in sperm decreased in the medium and high dose groups. The results of HE staining showed that the spermatogenic epithelium was disordered and the arrangement of spermatogenic cells were loose in the low dose group, the spermatogenic gap was enlarged in the middle dose group, and the cells in the high dose group were vacuolated and even azoospermic. The results of serum sex hormone levels showed that the serum testosterone levels decreased in each dose group, the serum follicle-stimulating hormone levels decreased in the medium and high dose groups, and the serum luteinizing hormone levels decreased in the high dose group (P<0.05). The iron content in the testicular tissue homogenate of the high dose group increased (P<0.05). The levels of GSH and SOD in the homogenate of testicular tissue decreased in the medium and high dose groups, while the levels of MDA increased (P<0.05). The results of Western blotting showed that the protein expression level of GPX4 in the testis in the high dose group was lower than that in the control group. The protein expression levels of SLC7A11 in the medium and high dose groups were lower than that in the control group. The results of correlation analysis showed that the expression level of GPX4 was positively correlated with sperm count, and negatively correlated with MDA level (P<0.05). SLC7A11 expression level was positively correlated with sperm count, and negatively correlated with sperm malformation rate and MDA level (P<0.05). Conclusion PS-MPs exposure leads to decreased sperm quality, testicular damage, and decreased serum sex hormone levels in male mice, and its mechanism of action may involve ferroptosis.
5.Spermine Synthase : A Potential Prognostic Marker for Lower-Grade Gliomas
Chen LIU ; Hongqi LI ; Xiaolong HU ; Maohui YAN ; Zhiguang FU ; Hengheng ZHANG ; Yingjie WANG ; Nan DU
Journal of Korean Neurosurgical Society 2025;68(1):75-96
Objective:
: The objective of this study was to assess the relationship between spermine synthase (SMS) expression, tumor occurrence, and prognosis in lower-grade gliomas (LGGs).
Methods:
: A total of 523 LGG patients and 1152 normal brain tissues were included as controls. Mann-Whitney U test was performed to evaluate SMS expression in the LGG group. Functional annotation analysis was conducted to explore the biological processes associated with high SMS expression. Immune cell infiltration analysis was performed to examine the correlation between SMS expression and immune cell types. The association between SMS expression and clinical and pathological features was assessed using Spearman correlation analysis. In vitro experiments were conducted to investigate the effects of overexpressing or downregulating SMS on cell proliferation, apoptosis, migration, invasion, and key proteins in the protein kinase B (AKT)/epithelialmesenchymal transition signaling pathway.
Results:
: The study revealed a significant upregulation of SMS expression in LGGs compared to normal brain tissues. High SMS expression was associated with certain clinical and pathological features, including older age, astrocytoma, higher World Health Organization grade, poor disease-specific survival, disease progression, non-1p/19q codeletion, and wild-type isocitrate dehydrogenase. Cox regression analysis identified SMS as a risk factor for overall survival. Bioinformatics analysis showed enrichment of eosinophils, T cells, and macrophages in LGG samples, while proportions of dendritic (DC) cells, plasmacytoid DC (pDC) cells, and CD8+ T cells were decreased.
Conclusion
: High SMS expression in LGGs may promote tumor occurrence through cellular proliferation and modulation of immune cell infiltration. These findings suggest the prognostic value of SMS in predicting clinical outcomes for LGG patients.
6.Application of In-fusion Cloning Technology as a Teaching Example in the Molecular Biology Laboratory(A National First-class Undergraduate Course)
Jing LUO ; Ya-Nan LI ; Yi-Di WANG ; Dong YANG ; Li TONG ; Hong-Yu SHEN ; Yan-Xia YIN
Chinese Journal of Biochemistry and Molecular Biology 2025;41(10):1552-1558
In-fusion cloning technology,as a revolutionary and efficient molecular biology tool,has been applied in multiple research fields such as basic biology,biotechnology,and biomedicine.In this article,we introduce a teaching reform project suitable for undergraduate students in the course of"Molecular Bi-ology Laboratory",which utilizes in-Fusion cloning technology to construct a prokaryotic expression vector for alkaline phosphatase mutant genes.Through specific teaching cases,we systematically explored the design and implementation of experimental projects,and focused on analyzing the key and difficult points of the teaching content.Our teaching practice has found that the implementation of this educational re-form project has achieved very good results in enhancing students' core biological literacy,bioinformatics skills,research thinking,and innovation abilities.At the same time,the application of this technology can significantly improve the quality of experimental teaching,providing new ideas and practical refer-ences for promoting the reform and innovation of National First-Class Courses.
7.Prevalence and influencing factors of chronic somatic comorbidities in patients with schizophrenia in Shanghai communities
Wei-bo ZHANG ; Jiang-nan LI ; Yan-li LIU ; Yi-zhou JIANG ; Yi ZHU ; Na WANG ; Jun CAI
Fudan University Journal of Medical Sciences 2025;52(4):484-491,499
Objective To investigate the prevalence of chronic somatic comorbidities in schizophrenic patients in Shanghai communities,and to explore the factors influencing comorbidities.Methods Based on Shanghai community-based severe mental disorders cohort,5 422 patients with schizophrenia(SCZ)were included in the study.12 common chronic somatic diseases,defined by patients'self-report,were selected to analyze the prevalence of comorbidity,and Logistic regression model was used to analyze the factors influencing the number of somatic comorbidities.Results The total prevalence of somatic comorbidity was 37.0%in 5 422 patients with SCZ,with the highest prevalence of hypertension(22.6%)and diabetes mellitus(13.1%)among 12 somatic diseases selected.Older age was the main factor associated with chronic somatic comorbidities in community schizophrenic patients.The risk of 1-2 comorbidities in patients aged≥60 years was 3.34(95%CI:2.74-4.07)times higher than those aged<45 years,while the risk of≥3 comorbidities was 3.27(95%CI:2.11-5.09)times higher,correspondingly.Female gender,marriage,smoking,and longer duration of illness were also risk factors for comorbidity.Women after menopause had higher risk of comorbidity than perimenopausal women.Conclusion Cardiovascular and metabolic diseases were common somatic comorbidities among schizophrenic patients in Shanghai communities.Older age,female gender,marriage,smoking,and longer duration of illness were risk factors for increasing number of comorbidities.
8.Investigation of effects of petroleum ether fraction from Derris eriocarpa on glucose and lipid metabolism in a mouse model of metabolic syndrome via ATF3/HNF4ɑ/CYP7A1 pathway
Jing YAN ; Jie WENG ; Xuan ZHANG ; Xue LI ; Chao-nan KONG ; Hong-cun LIU ; Li-fang YANG ; Ming-guo JIANG ; Qiu-yan LIANG ; Li-ting HE
Chinese Traditional Patent Medicine 2025;47(9):2902-2911
AIM To investigate effects of petroleum ether fraction from Derris eriocarpa How on glucose and lipid metabolism in a mouse model of metabolic syndrome(MS).METHODS KM mice were fed a high-fat diet and administered streptozotocin intraperitoneally to establish MS models.The MS mice were then randomly assigned to the model group,the metformin hydrochloride group,the lovastatin group,the ursolic acid group,and the high-,medium-and low-dose D.eriocarpa petroleum ether fraction groups,with 10 mice in each group.Ten additional mice maitained on a normal diet served as the normal control group.After 4 weeks of intragastric administration,glucose and lipid metabolism indicators were measured.Hepatic pathological changes were assessed using HE staining and oil red O staining.Liver tissue mRNA expressions of ATF3,PEPCK,FXR,CYP7A1,HNF4ɑ,CYP8B1 and SRB1 were quantified by RT-qPCR.Hepatic protein expressions of ATF3,HNF4ɑ,PEPCK,FXR and CYP7A1 was analyzed by Western blot in MS mice.RESULTS Compared to the model group,the high-dose D.eriocarpa petroleum ether fraction group exhibited significant glucose tolerance improvement(reduced OGTT-AUC,P<0.01);favorable serum lipid modulation in terms of increased HDL-C levels(P<0.01)and decreased TG,TC,LDL-C(P<0.01);reduced renal biomarkers(BUN,SCR)and hepatotoxic indicators of TBA,AST and ALT activities(P<0.01);alleviated hepatic lipid accumulation and histopathological damage;downregulated mRNA and protein expressions of ATF3,HNF4ɑ and PEPCK,as well as CYP8B1 mRNA expression(P<0.01);and upregulated mRNA and protein expressions of FXR and CYP7A1,along with SRB1 mRNA expression(P<0.01).CONCLUSION D.eriocarpa petroleum ether fraction ameliorates glucose and lipid metabolism dysregulation in MS mice by modulating the ATF3/HNF4ɑ/CYP7A1 signaling pathway,consequently eliciting hypoglycemic,hypolipidemic,hepatoprotective and nephroprotective effects.
9.The value of deep learning image reconstruction algorithm to improve the quality of low keV monochromatic portal vein images of energy spectrum CT
Li SHEN ; Taiping HE ; Qian TIAN ; Nan YU ; Dong HAN ; Zhanli REN ; Yongjun JIA ; Yangyang YAN
Journal of Practical Radiology 2025;41(4):664-668
Objective To explore the value of deep learning image reconstruction(DLIR)algorithm to improve the quality of low keV monochromatic portal vein images of energy spectrum CT.Methods Fifty patients who underwent enhanced upper abdominal energy spectrum CT scan were selected.Mixed-model adaptive statistical iterative reconstruction-Veo(50%ASIR-V)algorithm and high-deep learning image reconstruction(DLIR-H)algorithm were used to obtain monochromatic images at 40-70 keV(with intervals of 10 keV).The CT and standard deviation(SD)values of the portal vein trunk,left and right branches,and erector spinae muscle were measured in the transverse position,and the signal-to-noise ratio(SNR)and portal vein contrast-to-noise ratio(CNR)were calculated for objective evaluation.The portal vein image quality between the two algorithms and different energy was subjectively scored by two physicians.Results In terms of objective evaluation:compared with 50%ASIR-V,the CNR and SNR of portal vein in monochromatic DLIR-H images at the same keV between 40-70 keV energy levels were increased while the SD value was decreased(P<0.05),and the CT value was unchanged;there was no statistical difference in the magnitude of change in CNR between the two algorithms at different energy levels(P>0.05);there was a statistically significant difference in the magnitude of change in SNR and SD value(P<0.05)and the magnitude of change was the largest at 40 keV;comparison between different energy levels of DLIR-H,the CNR and SD value of 40 keV DLIR-H were the highest(P<0.05),and there was no significant difference in the SNR(P>0.05).In terms of subjective evaluation:there was no significant difference between the subjective scores of the two algorithms at the same keV from 40-70 keV(P>0.05),and the two reconstruction algorithms at 40 keV and 50 keV had the highest subjective scores between different keV.Conclusion The DLIR algorithm can reduce the noise of low keV monochromatic images,improve the image quality of portal vein.
10.Wu Jutong's Diagnosis and Treatment of Evil Invading Shaoyang
Manrou YAN ; Nan LI ; Jingsi FU ; Linlin QIAN ; Xiaobei MA
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(4):431-435
Wu Jutong's academic thoughts are inherited from Ye Tianshi and traced back to Zhongjing,and have a unique under-standing and play of the evil invading Shaoyang.Wu Jutong believes that Shaoyang has two major functional characteristics:ascending and pivoting.The principle of treating evil invading Shaoyang is to follow the ascending nature of Shaoyang and restore the pivoting function of Shaoyang.For Shaoyang fire-heat syndrome,follow Shaoyang to ascend and disperse to penetrate heat,and often use light,scavenging and dispersing products;for Shaoyang phlegm-fluid syndrome,creat Xiangfu Xuanfuhua Decoction to benefit the liver and gallbladder and resolve phlegm-fluid;for malaria invading Shaoyang,turn the pivot to stop malaria,and use Xiaochaihu Decoction and Qinghao Biejia Decoction for the treatment;for yin evil invading Shaoyang and Jueyin,Xiao Chaihu Decoction and Bupleurum chinense DC.are often used to turn the pivot of Shaoyang and warm and unchoke Jueyin.The contraindications of Xiao Chaihu Decoction are al-so summarized.

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