1.Mechanism Exploration of Doxorubicin and Sepsis Induced Myocardial Injury: Differences and Convergences
Tao ZHANG ; Zihan NAN ; Lixia LIU ; Jiaqi LIU ; Xiukai CHEN ; Xiaoting WANG ; Suwen SU
Medical Journal of Peking Union Medical College Hospital 2026;17(1):23-32
Doxorubicin (DOX)-induced cardiotoxicity and sepsis-induced myocardial injury (SIMI) represent significant clinical challenges in patients undergoing chemotherapy, sharing a common pathological basis of oxidative stress and mitochondrial dysfunction. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has recently been shown to play a critical role in DOX-induced cardiotoxicity and lipopolysaccharide (LPS)-induced SIMI. This article systematically reviews the mechanisms underlying myocardial injury caused by DOX and sepsis, identifying ferroptosis as a central common pathway. DOX triggers a burst of reactive oxygen species within mitochondria and inhibits glutathione peroxidase 4 (GPX4) activity through redox cycling of its quinone group and high-affinity accumulation in mitochondrial cardiolipin. LPS, by activating pattern recognition receptors and related inflammatory signaling pathways, provokes a cytokine storm and mitochondrial dysfunction. Both can disrupt the core regulatory axis of cysteine-glutathione (GSH)-GPX4, synergistically promoting ferroptosis in cardiomyocytes. Moreover, epigenetic regulation plays a key role in DOX- and LPS-induced cardiomyocyte ferroptosis and may serve as a promising therapeutic target. A deeper understanding of the ferroptosis mechanism and its epigenetic regulatory network in the synergistic injury induced by DOX and sepsis is of great importance for developing novel strategies to mitigate chemotherapy-related cardiotoxicity and improve outcomes in cancer patients with concurrent infections.
2.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.
3.Analysis of one year follow up on anisometropia changes among primary school students in Beihai
WANG Wei, OU Shengyu, ZHAN Lixia
Chinese Journal of School Health 2026;47(2):246-249
Objective:
To analyze the one year follow up changes and influencing factors of anisometropia among primary school students in Beihai, so as to provide data support for formulating targeted prevention and control strategies.
Methods:
In 2023 and 2024, visual acuity and refractive screening were conducted on primary school students in Beihai. A cohort matching method was used based on unique identifiers to link data from 2023 (baseline) Grades one to five with those from 2024 (follow up) Grades two to six, obtaining a total of 59 743 complete datasets. McNemar test and generalized estimating equations(GEE) model were employed to analyze the changing patterns of anisometropia.
Results:
The detection rate of anisometropia among primary school students in Beihai increased from 10.88% in 2023 to 12.30% in 2024 ( χ 2=97.12, P <0.01). Among them, the detection rate in Grade 1 decreased from 8.82% in 2023 to 7.50% in 2024, Grade 3 increased from 10.15% to 11.52%, Grade 4 increased from 12.10 % to 15.22%, Grade 5 increased from 14.61% to 17.88% ( χ 2=16.51,18.03,95.52,95.95,all P <0.05). The GEE results showed that the risk of anisometropia development was higher in girls than in boys ( OR =1.15), the risk of anisometropia increased by 16% with each 1 year increment in age ( OR =1.16) among primary school students, the risk of anisometropia development in Grade 5 was 2.20 times higher than that in Grade 1 ( OR =2.20)(all P <0.05). In lower grades, only the baseline anisometropia status in lower grades had a statistically significant effect on anisometropia among primary school students( OR =59.09), while the positive effects of gender and age difference gradually emerged and strengthened in middle and higher grades (all P <0.05).
Conclusions
The detection rate of anisometropia among primary school students in Beihai shows dynamic changes and influencing factors vary by grade level. It is necessary to develop stratified prevention and control strategies tailored to different grades.
4.Effect of Shixiaosan on Neurological Function and Ferroptosis in Rats with Cerebral Ischemia-reperfusion Injury Based on Nrf2/SLC7A11/GPX4 Signaling Pathway
Ying WEI ; Lixia WANG ; Junjun YIN ; Xiaohong CHEN ; Lijuan SONG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):22-31
ObjectiveTo investigate whether Shixiaosan can improve neurological function and inhibit ferroptosis in rats with cerebral ischemia-reperfusion injury (CIRI) by regulating the nuclear factor E2-related factor 2 (Nrf2)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) pathway. MethodsA rat model of CIRI was established using the intraluminal filament method. Briefly, cervical blood vessels were separated, branches of the external carotid artery were ligated, and the common carotid artery and internal carotid artery were clamped. A nylon filament was inserted through the opening of the external carotid artery to the origin of the middle cerebral artery to block blood flow and induce cerebral ischemia. After 60-120 min of ischemia, the filament was withdrawn to restore blood flow, and the external carotid artery incision was ligated. The rats were divided into a CIRI group, a Shixiaosan low-dose (-L) group (intragastric administration of 1.26 g·kg-1 Shixiaosan), a Shixiaosan high-dose (-H) group (intragastric administration of 2.52 g·kg-1 Shixiaosan), a donepezil hydrochloride tablet (DON) group (intragastric administration of 0.45 mg·kg-1 DON), and a Shixiaosan -H + Nrf2 inhibitor (ML385) group (intragastric administration of 2.52 g·kg-1 Shixiaosan combined with intraperitoneal injection of 30 mg·kg-1 ML385). An additional 12 rats underwent cervical artery separation followed by incision suturing and served as the control group. Equal volumes of double-distilled water were administered to the CIRI and control groups. Neurological function impairment was assessed using the modified Garcia JH score. Magnetic resonance imaging was used to determine the cerebral infarct volume ratio. Hematoxylin-eosin (HE) staining and Prussian blue staining were performed to observe neuronal injury and iron accumulation in the ischemic penumbra, respectively. Transmission electron microscopy was used to examine the ultrastructure of neuronal mitochondria in the ischemic penumbra. Commercial kits were used to measure ferrous iron (Fe2+), malondialdehyde (MDA), reduced glutathione (GSH) content, and reactive oxygen species (ROS) activity in the ischemic penumbra. The BODIPY (581/591) C11 fluorescent probe was used to detect intracellular lipid peroxidation levels. Western blot was performed to detect protein expression levels of Nrf2, SLC7A11, GPX4, transferrin receptor 1 (TFRC), ferritin heavy chain (FHC), and ferritin light chain (FLC) in the ischemic penumbra. ResultsCompared with the control group, the CIRI group exhibited neuronal injury in the ischemic penumbra, characterized by reduced neuron numbers, nucleolar shrinkage, and interstitial edema. Marked iron accumulation was observed in the tissue. Neuronal mitochondria showed atrophy and rupture, with reduced mitochondrial cristae and increased membrane density. The cerebral infarct volume ratio, Fe2+ content, MDA content, ROS activity, and lipid peroxidation levels were increased, whereas the modified Garcia JH score, GSH content, and protein expression levels of Nrf2, SLC7A11, GPX4, FHC, and FLC were decreased, and TFRC protein expression was increased (P<0.05). Compared with the CIRI group, the Shixiaosan -L group, Shixiaosan -H group, and DON group showed attenuated neuronal injury in the ischemic penumbra, reduced iron accumulation, alleviated mitochondrial damage, decreased cerebral infarct volume ratio, Fe2+ and MDA contents, ROS activity, and lipid peroxidation levels, as well as increased modified Garcia JH scores, GSH content, and protein expression levels of Nrf2, SLC7A11, GPX4, FHC, and FLC, while TFRC protein expression was decreased (P<0.05). The magnitude of changes in all indicators was greater in the Shixiaosan -H group than in the Shixiaosan -L group (P<0.05). Compared with the Shixiaosan -H group, all measured indicators in the Shixiaosan -H + ML385 group showed opposite trends (P<0.05). ConclusionShixiaosan may inhibit ferroptosis and restore neurological function in rats with CIRI by activating the Nrf2/SLC7A11/GPX4 pathway.
5.Application value of fibrosis-4 index and liver transient elastography in liver fibrosis risk stratification for metabolic associated fatty liver disease in community health institutions
Haiqing GUO ; Yaning LI ; Xiaohui LIU ; Jing ZHANG ; Yumin WANG ; Li CAO ; Lixia QIU
Journal of Clinical Hepatology 2026;42(6):1294-1300
ObjectiveTo perform metabolic associated fatty liver disease (MAFLD) screening among individuals attending community health institutions, to identify the patients at a low, moderate or high risk of advanced liver fibrosis based on fibrosis-4 index (FIB-4) and liver stiffness measurement (LSM) measured by liver transient elastography, and to implement stratified management. MethodsA cross-sectional study was conducted among 630 individuals attending Beijing Baizhifang Community Health Service Center from January to July 2024, and they were divided into MAFLD group and non-MAFLD group. According to body mass index (BMI), the MAFLD group was further divided into lean MAFLD group (BMI<23 kg/m2) and non-lean MAFLD group (BMI≥23 kg/m2). The above groups were compared in terms of demographic features, laboratory markers, hepatic steatosis, and LSM. Fibrosis risk stratification was performed for MAFLD patients based on FIB-4 and LSM, and a closed-loop management system involving referral to tertiary hospitals and follow-up at community health institutions was implemented. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. ResultsThere were 445 individuals (70.6%) in the MAFLD group and 185 individuals (29.4%) in the non-MAFLD group. Compared with the non-MAFLD group, the MAFLD group had a significantly lower proportion of male individuals (χ2=4.299, P<0.05), a significant reduction in the level of high-density lipoprotein cholesterol (Z=3.484, P<0.05), and significant increases in body weight (Z=-7.366, P<0.05), BMI (Z=-9.740, P<0.05), waist circumference (Z=-6.397, P<0.05), hip circumference (Z=-6.935, P<0.05), alanine aminotransferase (ALT) (Z=-2.765, P<0.05), fasting blood glucose (Z=-3.646, P<0.05), triglyceride (TG) (Z=-6.569, P<0.05), total cholesterol (Z=-2.033, P<0.05), low-density lipoprotein cholesterol (Z=-2.935, P<0.05), controlled attenuation parameter (CAP) (Z=-19.784, P<0.05), and LSM (Z=-5.703, P<0.05). Within the MAFLD group, there were 124 individuals (27.9%) in the lean MAFLD group and 321 individuals (72.1%) in the non-lean MAFLD group. Compared with the non-lean MAFLD group, the lean MAFLD group had significantly lower body weight (Z=-12.414, P<0.05), BMI (Z=-16.363, P<0.05), waist circumference (Z=-7.733, P<0.05), hip circumference (Z=-8.595, P<0.05), ALT (Z=-2.835, P<0.05), aspartate aminotransferase (Z=-1.972, P<0.05), TG (Z=-2.407, P<0.05), CAP (Z=-4.429, P<0.05), degree of steatosis (χ2=16.588, P<0.05), and LSM (Z=-3.908, P<0.05). Based on the results of FIB-4 and LSM, 76 patients at a moderate or high risk of liver fibrosis should be referred to a higher-level hospital for further management. ConclusionThe detection rate of MAFLD reaches 70.6% among the individuals attending community health institutions, among whom 76 (17.1%) should be referred to a higher-level hospital. Establishing a liver fibrosis risk stratification and management system based on FIB-4 and LSM among MAFLD individuals in communities provides a practical pathway for chronic disease management and referral system construction in community health institutions.
6.Exploring Content and Distribution Patterns of 22 Ginsenosides in Stems and Leaves of Panax ginseng with Different Stem Colors by UHPLC-QqQ-MS
Tianxin ZHANG ; Yang YANG ; Jiabing ZHANG ; Lixia WANG ; Xiaoxu CHEN ; Xiaoyu ZHU ; Dade YU ; Hongwei WU ; Zhuju WANG ; Kaiyang LIU ; Liying TANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):198-209
ObjectiveTo systematically elucidate the accumulation characteristics of secondary metabolites in the stems and leaves of Panax ginseng with different stem colors. MethodsUltra-high-performance liquid chromatography-triple quadrupole-tandem mass spectrometry (UHPLC-QqQ-MS) was employed to determine the of 22 ginsenosides in the stems and leaves of 2- to 5-year-old P. ginseng plants with green and purple stems. Principal component analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA), and one-way analysis of variance (ANOVA) were performed to explore the distribution patterns of ginsenosides from three dimensions: tissue distribution, growth duration, and stem color. Results① Tissue distribution: Leaves served as the primary organ for ginsenoside accumulation, exhibiting significantly higher total ginsenoside content than stems, which indicated distinct tissue-specific distribution of ginsenosides. ② Growth duration: Ginsenoside levels in stems generally peaked in the 2-year-old plants before stabilizing, while those in leaves displayed a declining-rebounding pattern, indicating that the 2-year-old plants (harvest stage) was a critical time point for the resurgence of leaf ginsenosides. ③ Stem color: A stage-specific correlation was observed between stem color and ginsenoside accumulation. In stems, the early-growth stage (2-year-old) of purple-stemmed plants exhibited higher content of specific ginsenosides (e.g., ginsenoside Rk1 and notoginsenoside R1), which may be associated with its stronger early-stage stress resistance. In leaves, the content of core ginsenosides (e.g., ginsenosides Re and Rd) in 5-year-old plants with green stems showed a surpassing trend, demonstrating higher potential of resource development. ConclusionThe accumulation of ginsenosides in P. ginseng stems and leaves is multidimensionally regulated by tissue type, growth duration, and stem color phenotypes. Purple-stemmed plants exhibit early-stage specific ginsenoside accumulation and stress resistance potential, whereas green-stemmed plants are more advantageous for core leaf ginsenoside development at the harvest stage. The findings confirm that aboveground stem color can serve as a biomarker for directed breeding and efficient resource utilization of P. ginseng.
7.Exploring Content and Distribution Patterns of 22 Ginsenosides in Stems and Leaves of Panax ginseng with Different Stem Colors by UHPLC-QqQ-MS
Tianxin ZHANG ; Yang YANG ; Jiabing ZHANG ; Lixia WANG ; Xiaoxu CHEN ; Xiaoyu ZHU ; Dade YU ; Hongwei WU ; Zhuju WANG ; Kaiyang LIU ; Liying TANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):198-209
ObjectiveTo systematically elucidate the accumulation characteristics of secondary metabolites in the stems and leaves of Panax ginseng with different stem colors. MethodsUltra-high-performance liquid chromatography-triple quadrupole-tandem mass spectrometry (UHPLC-QqQ-MS) was employed to determine the of 22 ginsenosides in the stems and leaves of 2- to 5-year-old P. ginseng plants with green and purple stems. Principal component analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA), and one-way analysis of variance (ANOVA) were performed to explore the distribution patterns of ginsenosides from three dimensions: tissue distribution, growth duration, and stem color. Results① Tissue distribution: Leaves served as the primary organ for ginsenoside accumulation, exhibiting significantly higher total ginsenoside content than stems, which indicated distinct tissue-specific distribution of ginsenosides. ② Growth duration: Ginsenoside levels in stems generally peaked in the 2-year-old plants before stabilizing, while those in leaves displayed a declining-rebounding pattern, indicating that the 2-year-old plants (harvest stage) was a critical time point for the resurgence of leaf ginsenosides. ③ Stem color: A stage-specific correlation was observed between stem color and ginsenoside accumulation. In stems, the early-growth stage (2-year-old) of purple-stemmed plants exhibited higher content of specific ginsenosides (e.g., ginsenoside Rk1 and notoginsenoside R1), which may be associated with its stronger early-stage stress resistance. In leaves, the content of core ginsenosides (e.g., ginsenosides Re and Rd) in 5-year-old plants with green stems showed a surpassing trend, demonstrating higher potential of resource development. ConclusionThe accumulation of ginsenosides in P. ginseng stems and leaves is multidimensionally regulated by tissue type, growth duration, and stem color phenotypes. Purple-stemmed plants exhibit early-stage specific ginsenoside accumulation and stress resistance potential, whereas green-stemmed plants are more advantageous for core leaf ginsenoside development at the harvest stage. The findings confirm that aboveground stem color can serve as a biomarker for directed breeding and efficient resource utilization of P. ginseng.
8.A study on the congenital hypodysfibrinogenemia family and its pathogenic mechanism
Jiawei ZHENG ; Xiaomei LU ; Lixia HAO ; Linna LU ; Jia YANG ; Lidong ZHAO ; Dongyan FU ; Duanyang WANG ; Gang WANG ; Linhua YANG
Chinese Journal of Hematology 2025;46(6):571-574
The proband was a 32-year-old female patient who sought medical attention for over 9 months of pregnancy, reduced fetal movement, and discomfort in the lower abdomen. The proband and her father had normal activated partial thromboplastin time and prothrombin time, decreased fibrinogen activity and antigen levels, and prolonged thrombin time, whereas the test results of her mother were normal. Ultrasonography showed intermuscular vein thrombosis in the left calf of the proband. Peripheral blood DNA was extracted from the proband and her parents, and Sanger sequencing was performed to detect the base sequences of the FGA, FGB, and FGG genes. The proband and her father had heterozygous missense mutations in exon 6 c.615A > C (p. Leu205Phe) and exon 8 c.1121A > C (p. Tyr374Ser) of the FGG gene. Bioinformatics analysis suggested that the two gene mutations may be the pathogenic mechanism of this congenital hypodysfibrinogenemia family.
9.Analysis of association of IL-23R gene polymorphisms with susceptibility for psoriasis
Quan GAN ; Lixia WANG ; Beibei WANG ; Manman ZHANG ; Mingliang DONG ; Beibei SU
Chinese Journal of Medical Genetics 2025;42(4):505-511
Objective:To assess the association of single nucleotide polymorphisms (SNPs) of interleukin-23 receptor ( IL-23R) gene with susceptibility to psoriasis. Methods:Two hundred and ten psoriasis patients admitted to Xinxiang Central Hospital from January 2019 to December 2024 were selected as the study group, and 210 healthy individuals undergoing physical examination during the same period were selected as the control group. 3 mL of peripheral venous blood sample was collected from each individual from the two groups, and PCR - Restriction fragment length polymorphism (PCR-RFLP) assay was used to determine the polymorphisms of the IL-23R gene at rs2201841, rs1004819, rs10889677, rs1343151 and rs1495965 loci. Genotypic and allelic distribution of each SNP locus was calculated to assess the association between SNPs of the IL-23R gene with the onset of psoriasis, and the difference in serum IL-23 levels among patients with different genotypes at each locus was compared. This study was approved by the Medical Ethics Committee of Xinxiang Central Hospital (Ethic No. 2024-749). Results:The results showed that the frequency of CC genotype at rs1004819 locus of the study group was significantly higher than that of the control group (26.19% vs. 18.10%, P<0.05), and the frequency of C allele was also significantly higher than that of the control group (54.05% vs. 42.62%, P<0.05). There was no significant difference in allelic and genotypic frequencies between the two groups at rs2201841, rs10889677, rs1343151, and rs1495965 loci ( P>0.05). The dominant and recessive inheritance patterns at the rs1004819 locus are associated with susceptibility to psoriasis ( P<0.05), while the different inheritance patterns at rs2201841, rs10889677, rs1343151, and rs1495965 loci are not associated with psoriasis ( P>0.05). The serum IL-23 levels of patients with CC genotype at the rs1004819 locus were higher than those with CT and TT genotypes ( P<0.05). No significant difference was detected in the serum levels of IL-23 between patients with different genotypes for the rs2201841, rs10889677, rs1343151, and rs1495965 loci ( P>0.05). Conclusion:The polymorphism at the rs1004819 locus of the IL-23R gene is associated with susceptibility to psoriasis, and individuals carrying the CC genotype and C allele have a higher risk of developing the disease.
10.A study of factors associated with neonatal necrotizing enterocolitis
Qiyue YANG ; Xinhua ZHANG ; Xiaoyun JIA ; Hao ZHOU ; Yanan KANG ; Xingyu WANG ; Lixia BAI
Chinese Journal of Epidemiology 2025;46(3):492-498
Objective:To explore the related risk factors of neonatal necrotizing enterocolitis (NEC) by constructing and comparing nine regression models.Methods:All NEC patients admitted to the neonatal internal medicine department, neonatal surgery department, and neonatal intensive care unit of Shanxi Provincial Children's Hospital (Shanxi Provincial Maternity and Child Health Center) from 2020 to 2022 were included as the case group. A control group consisted of children admitted during the same period based on the inclusion and exclusion criteria. The NEC data collected were used for feature selection by using the Boruta algorithm. Logistic regression, multi-decision tree gradient boosting, efficient gradient one-sided sampling, random forest, decision tree, gradient boosting decision tree (GBDT), neural network, support vector machine, and K-nearest neighbor models were constructed. The optimal model was selected through rigorous comparison and Shap explainable analysis was performed on the GBDT model.Results:Thirteen key factors were identified through screening for nine regression models construction. After strict comparison and analysis, the GBDT model showed higher stability compared with other eight regression models. In the validation set, the area under the receiver operating characteristic curve of the GBDT model was 0.958, with an accuracy of 0.925, and sensitivity and specificity of 0.827 and 0.950, respectively. Shap explainable analysis on the GBDT model revealed that suffering from anemia, non-invasive ventilator use, procalcitonin use, premature birth, and low birth weight increased the risk for NEC, while breastfeeding and probiotics decreased the risk for NEC.Conclusion:This study identified the risk factors and protective factors for NEC by using the GBDT model, which provided evidnce for the prevention and treatment of NEC.


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