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.Mechanism of Lijin manipulation regulating scar formation in skeletal muscle injury repair in rabbits
Kaiying LI ; Xiaoge WEI ; Fei SONG ; Nan YANG ; Zhenning ZHAO ; Yan WANG ; Jing MU ; Huisheng MA
Chinese Journal of Tissue Engineering Research 2025;29(8):1600-1608
BACKGROUND:Lijin manipulation can promote skeletal muscle repair and treat skeletal muscle injury.However,the formation of fibrosis and scar tissue hyperplasia are closely related to the quality of skeletal muscle repair.To study the regulatory effect of Lijin manipulation on the formation of fibrosis and scar tissue hyperplasia is helpful to explain the related mechanism of Lijin manipulation to improve the repair quality of skeletal muscle injury. OBJECTIVE:To explore the mechanism of Lijin manipulation to improve the repair quality of skeletal muscle injury in rabbits,thereby providing a scientific basis for clinical treatment. METHODS:Forty-five healthy adult Japanese large-ear white rabbits were randomly divided into blank group,model group and Lijin group,with 15 rats in each group.Gastrocnemius strike modeling was performed in both model group and Lijin group.The Lijin group began to intervene with tendon manipulation on the 3rd day after modeling,once a day,and 15 minutes at a time.Five animals in each group were killed on the 7th,14th and 21st days after modeling.The morphology and inflammatory cell count of gastrocnemius were observed by hematoxylin-eosin staining,the collagen fiber amount was observed by Masson staining,the expression of interleukin-6 and interleukin-10 in gastrocnemius was detected by ELISA.The protein and mRNA expressions of paired cassette gene 7,myogenic differentiation factor,myoblastogenin,alpha-actin,transforming growth factor beta 1,and type Ⅰ collagen were detected by western blot and RT-PCR,respectively,and the expression of type Ⅰ collagen protein was detected by immunohistochemistry. RESULTS AND CONCLUSION:Hematoxylin-eosin staining and Masson staining showed that compared with the model group,inflammatory cell infiltration and collagen fiber content decreased in the Lijin group(P<0.01),and the muscle fibers gradually healed.ELISA results showed that compared with the model group,the expression of interleukin-6 in the Lijin group continued to decrease(P<0.05),and the expression of interleukin-10 increased on the 7th day after modeling(P<0.05)and then showed a decreasing trend(P<0.05).Western blot and RT-PCR results showed that compared with the model group,the protein and mRNA expressions of paired cassette gene 7,myogenic differentiation factor,myoblastogenin in the Lijin group were significantly increased on the 14th day after modeling(P<0.05),but decreased on the 21st day(P<0.05);the protein and mRNA expressions of alpha-actin,transforming growth factor beta 1,and type Ⅰ collagen in the Lijin group were significantly decreased compared with those in the model group(P<0.05).Immunohistochemical results showed that the expression of type Ⅰ collagen in the Lijin group was significantly lower than that in the model group(P<0.05).To conclude,Lijin manipulation could improve the repair quality of skeletal muscle injury by inhibiting inflammation,promoting the proliferation and differentiation of muscle satellite cells,and reducing fibrosis.
5.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.
6.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.
7.Research Progress on Electrochemical Sensors for Monoamine Neurotransmitters
Yu ZHONG ; Yu ZHANG ; Xiu-Zhi KANG ; Jing SUN ; Cheng DONG ; Hong-Wei WU ; Yan-Zhao LI ; Nan LI
Chinese Journal of Analytical Chemistry 2025;53(9):1411-1421
Monoamine neurotransmitters mainly include serotonin,dopamine,epinephrine,and norepinephrine.They play an indispensable regulatory role in key physiological activities such as emotion,sleep,and memory within the central nervous system.Precise detection of these neurotransmitters holds great significance in the field of neuroscience research.Detection methods for monoamine neurotransmitters encompass high-performance liquid chromatography,mass spectrometry,capillary electrophoresis,fluorescence spectroscopy,and electrochemical methods,etc.Compared with other methods,electrochemical methods offer advantages such as high sensitivity,good selectivity,low cost,strong portability,convenient operation,and capability for in vivo real-time detection.This article reviewed recent research progress in electrochemical detection of monoamine neurotransmitters,focusing on a retrospective and summary from three aspects:sensor electrode materials,detection of various monoamine neurotransmitters,and in vivo real-time analysis.Furthermore,the future development of electrochemical sensors for monoamine neurotransmitters was prospected.
8.Recent Advances in Surface-Enhanced Raman Spectroscopy for Detection of Nano/Microplastics
Ayimureke ASIKAER ; Zhou ZHANG ; Sen-Sen ZHOU ; Ya-Nan XU ; You-Xin WANG ; Yan-Rong LI ; Dan LI
Chinese Journal of Analytical Chemistry 2025;53(10):1587-1596
Nano/microplastics(NMPs),due to their environmental persistence and resistance to degradation,have emerged as a major contributor to global pollution.NMPs are capable of adsorbing various hazardous chemicals and heavy metals,thereby posing threats to aquatic ecosystem health,which may ultimately cause potential risks to human health.Conventional analytical methods suffered from limited resolution,insufficient chemical information,or destruction of sample,invalidating these assays for on-site detection of NMPs.Surface-enhanced Raman scattering(SERS)offers distinct advantages such as high sensitivity,superior specificity,rich fingerprint information,and non-destructive analysis,thus facilitating the on-site analysis of NMPs in complex matrices.This review summarized recent advances in SERS substrates for detection of NMPs,discussed the construction and applications of SERS-based multimodal detection strategies,and introduced the research progress of SERS detection of NMPs in food safety,environmental pollution,and bioanalysis.Moreover,the main challenges and future directions of SERS-based NMP detection were outlined.
9.Construction of A Chiral Separation Method Using Polystyrene-cyclodextrin Metal-organic Framework Coating for Open-tubular Capillary Electrochromatography
Yan ZHANG ; Hao-Yu LI ; Cai LIU ; Rong-Yue ZHANG ; Xiao-Nan HE ; Juan QIAO
Chinese Journal of Analytical Chemistry 2025;53(10):1751-1760
By using a strategy of leveraging the ability of metal-organic frameworks(MOFs)materials to precisely regulate the spatial orientation of cyclodextrins(CD),a polystyrene-modified γ-cyclodextrin metal-organic frameworks(PS-CD-MOFs)capillary coating was established and applied to the chiral separation of amino acids in open-tubular capillary electrochromatography(OT-CEC)based on the excellent film-forming property of polystyrene(PS).Characterization results by Fourier transform infrared spectroscopy(FT-IR),X-ray diffraction(XRD)indicated that PS was successfully grafted onto the surface of CD-MOFs.The modification significantly improved the structural stability and thermal stability of CD-MOFs while maintaining the integrity of the MOFs.The PS-CD-MOFs coated capillary electrophoresis system exhibited excellent performance in separating dansylated amino acid enantiomers(Dns-D,L-AAs).Specifically,under the optimal separation conditions(Sodium dodecyl sulfate/boric acid buffer system,20 cm capillary,and 10 kV effective voltage),good separation was achieved for D,L-methionine(D,L-Met)and D,L-serine(D,L-Ser).Further quantitative analysis showed that Dns-D,L-Met presented a good linear relationship in the concentration range of 10.0-1500.0 μmol/L,with a correlation coefficient close to 0.998,demonstrating high sensitivity and repeatability.Not only did it overcome the problem that traditional CD(used as additives in capillary electrophoresis)could not precisely control the spatial orientation of chiral resolvents,but also it solved the issues of insufficient stability and bonding amount of CD-MOFs coatings by utilizing the excellent film-forming property of polymers on the inner wall of capillaries.This study provided an efficient and controllable new strategy for construction of chiral separation stationary phases.
10.Modeling methods and evaluation criteria in animal models of steroid-induced osteonecrosis of the femoral head
Xiuli WU ; Xiaoxia YAN ; Zhiqiang REN ; Nan SUN ; Jinju LI
Chinese Journal of Tissue Engineering Research 2025;29(21):4560-4567
BACKGROUND:Steroid-induced osteonecrosis of the femoral head is a key risk factor for non-traumatic femoral head necrosis,and the incidence of it has gradually increased in recent years,but its specific pathogenesis is still unclear,and finding a reasonable animal model is essential for disease research and treatment.OBJECTIVE:To review the commonly used animal models of steroid-induced osteonecrosis of the femoral head in recent years,and to analyze the advantages and disadvantages of different modeling methods and evaluation criteria,so as to provide a reference for follow-up research. METHODS:The articles published from 2013 to 2023 were searched in CNKI,WanFang Data,and PubMed with the keywords "femoral head necrosis,osteonecrosis of the femoral head,steroid-induced osteonecrosis of the femoral head,animal model." Finally,61 articles were involved for comprehensive analysis according to the inclusion criteria,including 38 English articles and 23 Chinese articles.RESULTS AND CONCLUSION:(1) Rabbits,rats,and chickens are the animals that are widely used in the study of steroid-induced osteonecrosis of the femoral head models. (2) Hormone combined with lipopolysaccharide or horse serum modeling has low mortality,high success rate,and strong stability. (3) Histopathology is the gold standard for the evaluation model,but the experiment needs to be terminated,which is not conducive to subsequent experimental research,so finding a non-invasive alternative method is still the direction of future efforts. (4) An ideal model of steroid-induced osteonecrosis of the femoral head has not yet been explored,and future researchers need to continue to strive to achieve breakthroughs in this field as soon as possible.

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