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.Efficacy and safety of Shuganning injection in treatment of liver injury: A clinical analysis
Qiaoxin WEI ; Mei LIU ; Daimeng SHI ; Shaoli YOU ; Yu CHEN ; Shuangsuo DANG ; Dongliang YANG ; Yuemin NAN ; Mingliang CHENG ; Zhongping DUAN
Journal of Clinical Hepatology 2026;42(6):1349-1357
ObjectiveTo investigate the efficacy and safety of Shuganning injection in the treatment of liver injury by observing the clinical outcome of patients with liver injury after treatment with Shuganning injection and comparing it with reduced glutathione (GSH). MethodsThis study was conducted among 175 patients with liver injury who attended 6 hospitals in China (Beijing YouAn Hospital, Capital Medical University; Nanyang First People’s Hospital; The Second Affiliated Hospital of Xi’an Jiaotong University; The Fifth Medical Center of Chinese PLA General Hospital; The Third Hospital of Hebei Medical University; The Affiliated Hospital of Guizhou Medical University) from April 25, 2019 to February 28, 2022. The patients were divided into experimental group (89 patients treated with Shuganning injection) and control group (86 patients treated with GSH), and the course of treatment was 4 weeks for both groups. Related indicators were recorded before treatment, after treatment, and after drug withdrawal for 8 weeks, including liver function parameters, blood biochemical parameters, blood lipids, coagulation profiles, liver fibrosis markers, traditional Chinese medicine (TCM) syndrome score, and ultrasound findings, as well as adverse events during treatment. The Wilcoxon rank-sum test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Wilcoxon signed-rank test was used for comparison of observation indicators before treatment, at week 4 of treatment, and after drug withdrawal for 8 weeks. When the efficacy evaluation of TCM syndromes was used as the outcome, a pooled analysis was performed for the effective cases and the markedly effective cases, and a Logistic regression model was used to calculate the odds ratio (OR) and its 95%CI. ResultsAfter 4 weeks of treatment with Shuganning injection, the patients showed significant reductions in TCM syndrome score (P<0.001) and the levels of aspartate aminotransferase, alanine aminotransferase, total bilirubin, and direct bilirubin (all P<0.001) and a significant increase in the level of albumin (P=0.002), and these significant improvements persisted after drug withdrawal for 8 weeks. Furthermore, compared with the control group, the experimental group had a significantly higher proportion of patients assessed as effective or markedly effective cases (48.31% vs 32.56%, P=0.033). Compared with the control group, the experimental group had a significantly greater change in TCM syndrome score at weeks 1-4 of treatment and after drug withdrawal for 8 weeks (P<0.05). At week 4 of treatment, the experimental group had a significantly greater reduction in alanine aminotransferase than the control group (P<0.05), and at week 8 after drug withdrawal, the experimental group had a significantly greater reduction in alanine aminotransferase and aspartate aminotransferase than the control group (all P<0.05). One patient in the experimental group (1.12%) experienced an adverse event, which was determined to be associated with the progression of viral hepatitis. ConclusionShuganning injection can effectively improve liver injury, with good long-term efficacy and a low incidence rate of adverse reactions.
3.Mechanism of tight junctional function injury of testicular Sertoli cells induced by high-fat diet based on NF-κB/NLRP3 signaling pathway
Run-min MAO ; Hai-xia ZHAO ; Hai-li DUAN ; Zi-hui GAO ; Ya-nan QU ; Guo-qing FU ; Jian-min MAO ; Jian-ming SUN ; Chang-cheng ZHANG
Chinese Pharmacological Bulletin 2025;41(11):2134-2142
Aim To investigate the effect of high-fat diet on the tight junction function injury of Sertoli cells through the NF-κB/NLRP3 signaling pathway in mice and to explore the underlying mechanism.Methods Male C57BL/6J mice were fed with high-fat or normal diet for five months.The body and gonadal organ weight of mice were measured,and their indices were calculated.The sperm concentration,the sperm viabili-ty,the testicular histomorphology and the expression levels of tight junction proteins ZO-1,Occludin and Claudin-11 were measured.TM4 cells were treated with palmitic acid(PA)for 24 h.Cell viability was detected by CCK-8 method.Then,TM4 cells were di-vided into different groups treated with PA(0,50,100,200 and 300 μmnol·L-1),and the expression lev-els of tight junction proteins ZO-1,Occludin and Clau-din-11 were detected by Western blot.The tight junc-tion permeability of TM4 cells were detected by transepithelial electrical resistance(TEER)and FITC-dextran.The expression levels of mRNA and proteins for the NF-κB/NLRP3 pathway-related factors were de-tected by RT-qPCR and Western blot.Results The results from animal experiments showed that high-fat diet increased body weight and seminal vesicle weight of mice,and decreased testicular index,epididymal in-dex,sperm concentration and sperm motility of mice.High-fat diet also caused testicular tissue structure damage and down-regulated the expression levels of tight junction proteins ZO-1 and Occludin,without af-fecting the expression of Claudin-11.In vitro,PA sig-nificantly down-regulated the expression levels of ZO-1,Occludin and Claudin-11 in TM4 cells,increased the cell permeability,as well as up-regulated the mRNA and protein expression levels of NLRP3/NF-κB signa-ling pathway-related factors in TM4 cells.Conclusions High-fat diet can impair the function of tight junction of testicualr Sertoli cells,and the machanism may be related to the activation of the NF-κB/NLRP3 signaling pathway,resulting in Sertoli cell inflammation in mice.
4.Mechanism of tight junctional function injury of testicular Sertoli cells induced by high-fat diet based on NF-κB/NLRP3 signaling pathway
Run-min MAO ; Hai-xia ZHAO ; Hai-li DUAN ; Zi-hui GAO ; Ya-nan QU ; Guo-qing FU ; Jian-min MAO ; Jian-ming SUN ; Chang-cheng ZHANG
Chinese Pharmacological Bulletin 2025;41(11):2134-2142
Aim To investigate the effect of high-fat diet on the tight junction function injury of Sertoli cells through the NF-κB/NLRP3 signaling pathway in mice and to explore the underlying mechanism.Methods Male C57BL/6J mice were fed with high-fat or normal diet for five months.The body and gonadal organ weight of mice were measured,and their indices were calculated.The sperm concentration,the sperm viabili-ty,the testicular histomorphology and the expression levels of tight junction proteins ZO-1,Occludin and Claudin-11 were measured.TM4 cells were treated with palmitic acid(PA)for 24 h.Cell viability was detected by CCK-8 method.Then,TM4 cells were di-vided into different groups treated with PA(0,50,100,200 and 300 μmnol·L-1),and the expression lev-els of tight junction proteins ZO-1,Occludin and Clau-din-11 were detected by Western blot.The tight junc-tion permeability of TM4 cells were detected by transepithelial electrical resistance(TEER)and FITC-dextran.The expression levels of mRNA and proteins for the NF-κB/NLRP3 pathway-related factors were de-tected by RT-qPCR and Western blot.Results The results from animal experiments showed that high-fat diet increased body weight and seminal vesicle weight of mice,and decreased testicular index,epididymal in-dex,sperm concentration and sperm motility of mice.High-fat diet also caused testicular tissue structure damage and down-regulated the expression levels of tight junction proteins ZO-1 and Occludin,without af-fecting the expression of Claudin-11.In vitro,PA sig-nificantly down-regulated the expression levels of ZO-1,Occludin and Claudin-11 in TM4 cells,increased the cell permeability,as well as up-regulated the mRNA and protein expression levels of NLRP3/NF-κB signa-ling pathway-related factors in TM4 cells.Conclusions High-fat diet can impair the function of tight junction of testicualr Sertoli cells,and the machanism may be related to the activation of the NF-κB/NLRP3 signaling pathway,resulting in Sertoli cell inflammation in mice.
5.Influence of Oatp4c1-P-gp transmembrane transport system in the kidneys of obese mice on the pharmacokinetics of digoxin
Jing-wen MEN ; Lu SUN ; Hao-ran YUE ; Zhao-yue DUAN ; Hui-nan HOU ; Ting GUI ; Jun-hong XIN ; Zhi-bo GAI
Chinese Pharmacological Bulletin 2025;41(7):1318-1324
Aim To investigate the expression of or-ganic anion transporting polypeptide 4C1(Oatp4c1)-P-glycoprotein(P-gp)in the kidneys of obese mice in-duced by high-fat diet(HFD),and its impact on the pharmacokinetic changes of digoxin.Methods C57BL/6 mice were randomly divided into the Chow group and the HFD group.Body weight and blood glu-cose were recorded weekly.After successful model es-tablishment,digoxin was intraperitoneally injected,and blood was collected at different time points.Part of the blood samples was used for LC-MS/MS detection,and the other part was used for the detection of other bio-chemical indicators.After 16 weeks,the organs were removed and weighed.HE and immunohistochemical staining was used to observe the renal pathology and the expression of Villin,a marker of proximal tubules.Western blot and qPCR were combined to detect the expression of Villin,Oatp4c1 and P-gp.Results In the HFD group,body weight and blood glucose in-creased significantly.The blood concentration of digox-in rose,the area under the curve increased,and the half-life was prolonged.The proximal tubular epithelial cells shed,and the protein expression of Villin,Oatp4c1 and P-gp decreased significantly.Conclu-sions The down-regulation of Oatp4c1-P-gp expres-sion in the kidneys of HFD mice leads to an increase in the blood concentration of digoxin and a decrease in re-nal clearance.
6.Comparison of the early postoperative efficacy between Kahook dual blade internal trabeculectomy and internal gonioscope-assisted transluminal trabe-culotomy in the treatment of primary open-angle glaucoma
Ying DUAN ; Mingxia CUI ; Yang ZHANG ; Lingbo SHU ; Nan LI
Recent Advances in Ophthalmology 2025;45(6):486-490
Objective To investigate the early postoperative efficacy between Kahook dual blade(KDB)internal tra-beculectomy and internal gonioscopy-assisted transluminal trabeculotomy(GATT)in the treatment of primary open-angle glaucoma(POAG).Methods A total of 120 patients(120 eyes)with POAG were included and divided according to dif-ferent surgical treatment methods.Among them,62 patients(62 eyes)undergoing internal trabeculectomy by KDB were di-vided into Group A,and 58 patients(58 eyes)undergoing GATT were divided into Group B.Relevant data of patients in the two groups were collected,and the efficacy of the two surgical methods was compared.Results The intraocular pres-sure in both groups decreased 1 day,1 week,and 1 month after surgery compared with preoperative levels(all P<0.05).However,there was no significant difference in the intraocular pressure measured at the above time points between the two groups(all P>0.05).The type of drugs for reducing the intraocular pressure in both groups decreased significantly 1 day,1 week,and 1 month after surgery compared with preoperative levels(all P<0.05).However,there was no significant difference in the type of drugs for reducing the intraocular pressure at the above time points between the two groups(all P>0.05).There was no statistically significant difference in the total incidence of complications between Group A(45.16%)and Group B(39.66%)(P>0.05).Specifically,the main complications in Group A included anterior chamber hemorrhage and intraocular pressure rebound,while those in Group B included anterior chamber hemorrhage and ciliary detachment.Conclusion Both KDB internal trabeculectomy and GATT can effectively reduce the intraocular pressure in patients with POAG and reduce the use of postoperative intraocular pressure-lowering drugs.There was no significant difference in surgical complications between the two surgical methods.The selection of surgical procedures in clinical prac-tice can be determined based on patients' wishes and actual situation.
7.Best evidence summary for nutritional management in adult with metabolic dysfunction-associated fatty liver disease
Nan WANG ; Jie ZHANG ; Peibei DUAN ; Zhenzhen SUN ; Li YANG
Modern Clinical Nursing 2025;24(1):59-67
Objective To summarise the evidence on nutritional management in adults with metabolic dysfunction-associated fatty liver disease(MAFLD),therefore to provide a guidance for clinical practice.Methods According to the"6S"model,literature on the nutritional management in adult MAFLD were retrieved from domestic and international databases and websites,including National Guide Library of the United States,National Institute for Health and Care Excellence,Guidelines International Network,the American Association for the Study of the Liver Disease,Europe Association for the Study of the Liver,Asian Pacific Association for the Study of the Liver,American Association of Clinical Endocrinologists,Italian Association for the Study of the Liver,European Society of Clinical Nutrition and Metabolism,American Society for Parenteral and Enteral Nutrition,BMJ Best Practice,UpToDate,Joanna Briggs Institute(JBI)Evidence database,PubMed,Cochrane Library,Web of Science,Embase,CINAHL,Medlive,CNKI,VIP,Wanfang,China Biology Medicine,from the inception of databases to 1st March,2024.The literature included guidelines,expert consensus,recommended practices,systematic reviews and evidence summaries.Two researchers independently evaluated the quality of literature and extracted data to summarise the best evidence.Results A total of 24 publication were finally included,with 36 pieces of best evidence summarised,covering six themes:assessment and goals,dietary patterns,diet structure,dietary supplements,exercise guidance and health education.Conclusion The best evidence on nutritional management summarised in this study provides the evidence-based support for healthcare providers with better nutritional management for adult MAFLD,it also offers a guidance in formulation of individualised nutritional management plans.
8.Analysis of 8 cases of primary mediastinal large B-cell lymphoma
Linlin ZHANG ; Chunju ZHOU ; Nan LI ; Shuang HUANG ; Meng ZHANG ; Ling JIN ; Jing YANG ; Yonghong ZHANG ; Yanlong DUAN
Chinese Journal of Pediatrics 2025;63(8):901-905
Objective:To investigate the clinical features, pathologic characteristics, treatment and prognosis of primary mediastinal large B-cell lymphoma (PMBCL) in children.Methods:Clinical data including clinical manifestations, treatment, clinical efficacy of 8 cases of childhood PMBCL treated in Beijing Children′s Hospital, Capital Medical University from March 2017 to February 2024 were collected retrospectively, the clinical characteristics and prognosis of them were summarized.Results:Among the 8 children, there were 5 males and 3 females. The age at the time of initial diagnosis was 11.0 (10.3, 13.5) years. The first clinical symptoms were cough (8 cases) and stridor (6 cases). The lesions most often involved the mediastinum (8 cases), lungs (5 cases, hilum more often), pericardium (5 cases), and pleura (4 cases). Extra thoracic invasion was present in 4 cases, 7 cases had huge tumor lesions and 7 cases were phase Ⅲ clinical stage. Except for 1 case who underwent surgical resection of the tumor, the remaining 7 cases were treated with DA-EPOCH+R (dose adjusted-etoposide+prednisone+vincristine+cyclo-phosphamide+doxorubicin+rituximab) chemotherapy. The follow-up time was 25.0 (10.5, 43.3) months, with 7 cases in complete and partial metabolism response, 1 case had disease progression. All 8 cases survived.Conclusions:PMBCL is most common in school-age boys and most of them present with huge mediastinal tumor focus. PMBCL expresses B-cell spectrum antigens and weakly expresses CD30.The application of DA-EPOCH+R is effective in the treatment of PMBCL in children.
9.Analysis of 7 cases of childhood blastic plasmacytoid dendritic cell neoplasm
Ziqing FENG ; Chunju ZHOU ; Ningning ZHANG ; Ling JIN ; Jing YANG ; Shuang HUANG ; Meng ZHANG ; Nan LI ; Yanlong DUAN
Chinese Journal of Pediatrics 2025;63(11):1207-1211
Objective:To evaluate the clinical characteristics, pathology, treatment and prognosis of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in children.Methods:Clinical data (including gender, age of disease onset, affected sites, treatment, timing of allogeneic hematopoietic stem cell transplantation (allo-HSCT), etc.) of 7 children with BPDCN who were admitted to Beijing Children′s Hospital, Capital Medical University from December 2018 to December 2023 were analyzed retrospectively. Clinical outcomes were also assessed, with patients followed up until December 2024.Results:Among 7 patients, there were 3 males and 4 females. Age at disease onset ranged from 3.2 to 12.9 years. Initial presentations included subcutaneous nodules in 5 cases, rash in 1 case, and ankle pain in 1 case. Extra-cutaneous involvement was seen in the bone marrow, lymph nodes, and central nervous system. Six patients received induction chemotherapy using a modified lymphoblastic lymphoma regimen, 1 patient received the high-risk protocol for pediatric lymphoblastic lymphoma/leukemia and salvage therapy regimens. Allo-HSCT was performed soon after chemotherapy remission. The time to bridge allo-HSCT was 3.5 to 6.5 months. The follow-up time was 1.6 to 6.0 years. Six patients were in disease-free survival, while 1 patient survived with disease after recurrence following transplantation.Conclusions:BPDCN is rare in children and presents diverse clinical manifestations, with skin involvement being the predominant feature. Early allo-HSCT following complete remission with chemotherapy can improve prognosis.
10.Biomechanical characteristics of lower limbs in female patients with different types of patellofemoral pain syndrome
Youqing DONG ; Zixuan WEI ; Haiou WU ; Ruixiong CHEN ; Peng DUAN ; Nan CHEN ; Xikai LIN
Chinese Journal of Tissue Engineering Research 2025;29(21):4458-4468
BACKGROUND:Currently,research both domestically and internationally on patellofemoral pain syndrome has explored the kinematics and dynamics during daily activities such as stair ascent and descent,and walking. However,there is a lack of studies examining the lower limb biomechanical characteristics of young female patients with patellofemoral pain syndrome in different squatting conditions.OBJECTIVE:To investigate the lower limb biomechanical characteristics among young female patients with patellofemoral pain syndrome in different functional states of the subtalar joint,providing theoretical support for the clinical treatment of various types of patellofemoral pain syndrome.METHODS:A total of 33 participants were included in this study. There were 10 subjects in the healthy control group (group C). The other 27 subjects with patellofemoral pain syndrome were divided into two groups according to the foot posture index:14 subjects in the normal subtalar joint group (group A,foot posture index 0-6 points) and 13 subjects in the abnormal subtalar joint group (group B,foot posture index 7-12 points). The biomechanical indices of thesubjects in each group were collected and compared when they walked on stairs at normal speed. The kinematic indices included the three-dimensional joint angles of the hip and knee and the sagittal plane joint angles of the ankle at the initial contact moment and the moment of maximum knee flexion angle during the stance period. The dynamic indices included the three-dimensional joint torques of the hip and knee and the sagittal plane joint torques of the ankle at the moment of maximum knee flexion angle during the stance period. The surface electromyography indices included the root mean square amplitudes of the vastus medialis,vastus lateralis,rectus femoris,semitendinosus and semimembranosus,biceps femoris,and gluteus medius in the pre-activation stage and the buffering stage.RESULTS AND CONCLUSION:(1) At the initial ground contact moment,group A exhibited a greater knee flexion angle (P<0.05),greater hip external rotation angle (P<0.01),and smaller knee external rotation angle (P<0.01) compared to group B. Compared to group C,group A showed a greater knee flexion angle and smaller hip flexion angle (both P<0.01). Group B demonstrated a greater knee external rotation angle and smaller hip external rotation angle and hip flexion angle (all P<0.01) compared to group C. (2) At the moment of maximum knee flexion,group A had a smaller knee valgus angle (P<0.05),smaller knee external rotation angle (P<0.05),and greater knee flexion angle (P<0.01) compared to group B. Compared to group C,group A showed a smaller knee valgus angle (P<0.05),smaller hip flexion angle (P<0.01),and smaller hip external rotation angle (P<0.05). Group B had a smaller knee flexion angle,hip flexion angle,hip external rotation angle,and greater knee external rotation angle (all P<0.01) compared to group C. Additionally,group A exhibited a greater hip internal rotation moment (P<0.05) and plantarflexion moment (P<0.01) compared to group C. (3) At normal speed during the staircase buffering phase,group C showed higher activation levels than group A in the vastus lateralis (P<0.05),vastus medialis (P<0.01),gluteus medius (P<0.01),and biceps femoris (P<0.05). Group C also had higher activation levels than group B in the vastus medialis (P<0.01),gluteus medius (P<0.01),and biceps femoris (P<0.05). Additionally,group A showed higher activation in the semitendinosus and semimembranosus muscles compared to group B (P<0.05). (4) These findings indicate that young female patients with patellofemoral pain syndrome have stiffer hip and knee joint buffering while descending stairs,potentially compensated by the ankle joint. Low muscle activation levels contribute to patellofemoral pain,with those having normal subtalar joints but experiencing pain showing the lowest and most abnormal activation. ③ Abnormal biomechanics in the normal subtalar joint group are mainly due to insufficient hip and knee flexion. Abnormal biomechanics in the abnormal subtalar joint group are mainly due to excessive subtalar joint pronation.

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