1.Construction of machine learning classification prediction model for vancomycin blood concentrations based on MIMIC-Ⅳ database
Xiaohui LIN ; Yujia WANG ; Lingling ZHANG ; Shuanglin XU
China Pharmacy 2025;36(19):2448-2453
		                        		
		                        			
		                        			OBJECTIVE To construct a classification prediction model for vancomycin blood concentration, and to optimize its precision dosing strategies. METHODS Patient records meeting inclusion criteria were extracted from the Medical Information Mart for Intensive Care database. Following data cleaning and preprocessing, a final cohort of 9 902 patient was analyzed. Feature selection was performed through correlation analysis and the Boruta feature selection algorithm. Vancomycin blood concentrations were discretized into three categories based on clinical therapeutic windows: low (<10 μg/mL), intermediate (10-20 μg/mL), and high (≥20 μg/mL). Six machine learning algorithms were employed to construct classification models: tabular prior-data fitted network (TabPFN), logistic regression (LR), random forest (RF), extreme gradient boosting (XGBoost), support vector machine (SVM), K-nearest neighbors (KNN). Model performance was evaluated using 10-fold cross-validation (10-CV), with primary metrics including: accuracy, balanced accuracy, precision macro, recall macro, macro F1, area under the receiver operating characteristic curve (OvR-AUC). Shapley Additive Explanations (SHAP) was adopted to analyze the direction and magnitude of the impact that different features had on the model’s predictive outcomes. RESULTS The results showed that the RF and TabPFN models performed the best (with accuracy of 0.741 4 and 0.737 7, and OvR-AUC of 0.907 0 and 0.895 8, respectively). XGBoost model exhibited moderate performance, while LR, SVM, and KNN models demonstrated relatively poor performance. Confusion matrix heatmap analysis revealed that both RF and TabPFN achieved higher accuracy in predicting high- concentration cases but exhibited slightly lower performance in the low and medium concentration categories. Bootstrap with 10-CV revealed that the RF model demonstrated stable performance across various evaluation metrics (accuracy: 0.741 4; balanced accuracy: 0.740 3; precision macro: 0.732 1; recall macro: 0.736 0; macro F1: 0.736 0; OvR-AUC: 0.907 0), indicating good classification performance and generalization ability. SHAP analysis revealed that creatinine, urea nitrogen, daily cumulative dose and administration frequency of vancomycin, which were key predictors, had a significant impact on the prediction results. CONCLUSIONS RF and TabPFN models demonstrate certain advantages in the classification prediction of vancomycin trough blood concentrations; however, their performance in the low to moderate concentration categories still requires improvement.
		                        		
		                        		
		                        		
		                        	
2.Effect of Icariin on Myocardial Remodeling in Rats Based on Vitamin D Regulation of Dendritic Cell Phenotype
Qian LI ; Yujia CHEN ; Yan ZHOU ; Wen LI ; Liancheng GUAN ; Huanzhen WANG ; Yunzhi CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):76-85
		                        		
		                        			
		                        			ObjectiveTo investigate the effect of icariin (ICA) on the phenotype of dendritic cells (DCs) in heart tissue of the Dahl salt-sensitive myocardial remodeling model of rats and its regulation on the vitamin D system. MethodsMale Dahl salt-resistant rats were divided into a normal group, and male Dahl salt-sensitive rats were divided into a model group, low-, medium-, and high-dose ICA groups (30, 60, 120 mg·kg-1·d-1), and Vitamin D group (3×10-5 mg·kg-1·d-1). In addition to the normal group, the other groups were given an 8% high salt diet to establish a myocardial remodeling model and received intragastric administration after successful modelling once a day for six weeks. The dynamic changes in tail artery blood pressure were monitored, and detection of cardiac ultrasound function in rats was performed. Hematoxylin-eosin (HE) staining and Masson staining were used to observe the morphological changes in rat heart tissue. The phenotype of DCs and T helper cell 17 (Th17)/regulatory T cell (Treg) ratio were detected by flow cytometry. The mRNA and protein expression of vitamin D receptor (VDR), 1α-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1), forkhead frame protein 3 (FoxP3), solitaire receptor γt (RORγt), myocardial type Ⅰ collagen (ColⅠ), and type collagen (ColⅢ) in heart tissue was detected by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot. ResultsCompared with the normal group, the model group showed disordered arrangement and rupture of myocardial cells, nuclear condensation, significant edema of myocardial tissue, significant proliferation of collagen fibers in a network distribution, and a significant increase in tail artery blood pressure, left ventricular end diastolic diameter (LVEDD), and left ventricular end systolic diameter (LVESD) (P<0.05). The phenotype of cardiac DCs was CD40, CD80, and CD86, and the levels of major histocompatibility complex Ⅱ (MHC-Ⅱ), Th17 cells, and Th17/Treg were significantly increased (P<0.05). The mRNA and protein expression of CYP24A1 and RORγt in the heart, as well as the mRNA expression of ColⅠ and ColⅢ, were significantly increased (P<0.05). The left ventricular ejection fraction (LVEF), interventricular septal thickness (IVSD), and left ventricular posterior wall thickness (LVPWD) were significantly decreased (P<0.05). The phenotype of cardiac DCs such as CD11, CD11b, and Treg cells, were significantly reduced (P<0.05), while the mRNA and protein expression of cardiac VDR, CYP27B1, and FoxP3 were significantly decreased (P<0.05). Compared with the model group, the low-, medium-, and high-dose ICA groups and vitamin D group significantly reduced myocardial cell rupture and nuclear consolidation in rats. The high-dose ICA group and vitamin D group showed a small amount of myocardial cell rupture and nuclear consolidation, improving myocardial fiber arrangement to varying degrees and significantly reducing myocardial fiber rupture and proliferation. The tail artery blood pressure, LVEDD, and LVESD were significantly decreased in the low-, medium-, and high-dose ICA groups and vitamin D group (P<0.05), and the phenotype of cardiac DCs including CD40, CD80, CD86, MHC-Ⅱ, Th17 cells, and Th17/Treg were significantly decreased (P<0.05). The mRNA and protein expression of CYP24A1 and RORγt, and the mRNA expression of ColⅠ and ColⅢ in the heart were significantly decreased in the medium- and high-dose ICA groups and vitamin D group (P<0.05). The LVEF, IVSD, and LVPWD of myocardial remodeling model rats in the low-, medium-, and high-dose ICA groups and vitamin D group were significantly increased (P<0.05). The phenotypes of cardiac DCs including CD11, CD11b, and Treg cells were significantly increased in the medium- and high-dose ICA groups and the Vitamin D group (P<0.05). The mRNA and protein expressions of VDR, CYP27B1, and FoxP3 in the heart were significantly increased in the medium- and high-dose ICA groups and vitamin D group (P<0.05). ConclusionICA can regulate tail artery blood pressure, cardiac structural and functional damage, and myocardial tissue fibrosis and inhibit phenotype and functional maturation of DCs in heart tissue in the myocardial remodeling model of Dahl salt-sensitive rats. It can also affect the gene and protein expression of VDR, CYP24A1, and CYP27B1, achieving its intervention in Th17/Treg balance in the immune process of myocardial remodeling possibly by regulating vitamin D/VDR in heart tissue. 
		                        		
		                        		
		                        		
		                        	
3.The effect and mechanism of Huangkui capsule pretreatment of human umbilical cord mesenchymal stem cell-derived exosomes on improving renal ischemia-reperfusion injury
Yawei YAO ; Jiahui HE ; Hao WANG ; Yutong WANG ; Ruiyan WANG ; Xingyu WAN ; Yujia LIU ; Xinghua LÜ
Organ Transplantation 2025;16(2):237-245
		                        		
		                        			
		                        			Objective To explore the effects and mechanisms of human umbilical cord mesenchymal stem cell (HUC-MSC)-derived exosomes (Exo) pretreated with Huangkui capsules on renal ischemia-reperfusion injury (IRI). Methods HUC-MSCs were cultured in media containing different concentrations of Huangkui capsules for 24 hours to determine cell viability and select an appropriate concentration for subsequent experiments. HUC-MSCs were pretreated with 50 μg/mL Huangkui capsules for 24 hours, and Exo were extracted using an exosome extraction kit. The morphology was observed under a transmission electron microscope, particle size was measured by nanoparticle tracking analysis, and the expression of exosomal membrane surface marker proteins was detected by Western blot. Human renal tubular epithelial cells (HK-2 cells) were randomly divided into hypoxia/reoxygenation group (M group), hypoxia/reoxygenation + Exo group (E group), and hypoxia/reoxygenation + Huangkui capsules pretreated Exo group (H group). Western blotting was used to measure the expression of endoplasmic reticulum stress (ERS)-related proteins, and real-time fluorescent quantitative reverse transcription polymerase chain reaction was used to measure the expression of ERS-related gene messenger RNA (mRNA). Mice were randomly divided into sham operation group (Sham group), ischemia-reperfusion group (I/R group), ischemia-reperfusion + Exo group (E group), and ischemia-reperfusion + Huangkui capsules pretreated Exo group (H group). Renal histological assessment, serum creatinine (Scr), blood urea nitrogen (BUN) measurement and inflammatory factor detection were performed 24 hours later. Results Both Exo and Huangkui capsules prereated Exo had a bilayer membrane structure and a cup-shaped morphology; their average particle sizes were 116.8 nm and 81.3 nm, respectively. Both expressed CD9, CD63, TSG101. Compared with the M group, the E group had decreased relative expression of transcription factor 6 (ATF6) and protein kinase R-like endoplasmic reticulum kinase (PERK) proteins, increased mRNA relative expression, increased relative expression of C/EBP homologous protein (CHOP) protein, and decreased mRNA relative expression. Compared with the E group, the H group had decreased relative expression of ATF6, PERK, CHOP proteins, and decreased mRNA relative expression of ATF6 and PERK (all P<0.05). Animal experimental results showed that compared with the Sham group, the I/R group had increased renal tubular injury scores, Scr, BUN, interleukin (IL)-1β, IL-10, IL-18, tumor necrosis factor (TNF)-α levels. Compared with the I/R group, the E and H groups had decreased renal tubular injury scores and Scr, BUN, IL-1β, IL-10, IL-18, TNF-α levels. Compared with the E group, the H group had decreased renal tubular injury scores and Scr, BUN, IL-1β, IL-10, IL-18, TNF-α levels (all P<0.05). Conclusions Huangkui capsules pretreatment HUC-MSC-derived Exo may alleviate renal IRI by inhibiting ERS.
		                        		
		                        		
		                        		
		                        	
4.Protective effect of brain-derived neurotrophic factor on retinal neurovascular unit
Suyu WANG ; Yujia YAO ; Jiajun LI ; Keran LI
International Eye Science 2024;24(2):216-220
		                        		
		                        			
		                        			 Based on the neurovascular unit(NVU), neurovascular coupling functions as a barrier to maintain the homeostasis of the microenvironment by regulating the signaling and metabolic activity of nerve cells and capillaries. Widely dispersed across the retina, the NVU is essential to preserving its normal physiological function. A disturbance in retinal neurovascular homeostasis produced by a range of factors can result in a variety of retinal disorders, such as diabetic retinopathy(DR), glaucoma, retinitis pigmentosa(RP)and age-related macular degeneration(ARMD). The retina also has a widespread distribution of brain-derived neurotrophic factor(BDNF), which functions to promote neuron growth and repair damage by binding to its receptor TrkB. In recent years, BDNF was found to play a protective role against damage in the early stage of retinal neurovascular homeostasis imbalance, often known as the neurodegenerative stage. It also helps to reduce the production of pro-angiogenic substances of neurological origin and offers a fresh approach for the early detection and treatment of associated eye disorders. 
		                        		
		                        		
		                        		
		                        	
5.A preliminary investigation of the key parameters of average value articulator based on mandibular movement trajectories in 100 adults with individual normal occlusion
Shenyao SHAN ; Yujia ZHU ; Junjie WANG ; Aonan WEN ; Zixiang GAO ; Qingzhao QIN ; Wenbo LI ; Yong WANG ; Yijiao ZHAO
Chinese Journal of Stomatology 2024;59(12):1228-1233
		                        		
		                        			
		                        			Objective:To explore the method of obtaining the key parameters of the average value articulator in healthy people based on mandibular movement trajectory data, with a view to providing a reference for the clinical application of the average value articulator.Methods:One hundred healthy volunteers (42 males and 58 females) with individual normal occlusion, aged 18-55 years old, who met the inclusion criteria were recruited from Beijing, and their mandibular movement trajectory data were collected. The left and right sagittal condylar inclination(SCI) and transversal condylar inclination(TCI) were obtained from the values of the articulator parameters which were generated in the mandibular movement analysis system.The SCI and TCI were grouped by gender and calculated separately for the two groups and the overall sample; the gender differences in the two parameters and the differences between the mean values of the two parameters and the average value articulator empirical values (35° for SCI and 15° for TCI) for the overall sample were compared.Results:The differences between SCI (35.8°±7.4°) and TCI [11.2° (11.3°)] in males and the corresponding parameters [35.6°±8.3° and 10.8° (9.5°), respectively] in females were not statistically significant ( t=0.10, P=0.922; Z=-0.60, P=0.552); the overall sample SCI (35.7°±7.9°) did not differ statistically from the average value articulator empirical value ( t=1.23, P=0.221), and the overall sample TCI [10.9° (10.3°)] was significantly smaller than the average value articulator empirical value ( W=5 825.00, P<0.001). Conclusions:The mandibular movement trajectory data of 100 adults with individual normal occlusion in this study shows that the gender factor does not affect the setting of the key parameters of the average value articulator, the SCI of the average value articulator empirical values is appropriate, and the TCI has the possibility of being on the large side. In the clinical use of the articulator to assist in the design of restorations, the parameter values should be rationally adjusted according to the actual situation of the patient′s dentition and mandibular movement.
		                        		
		                        		
		                        		
		                        	
6.Preliminary application study of digital technology for constructing three-dimensional facial symmetry reference planes in anterior dental esthetic restoration
Lijuan MA ; Xianghai YU ; Dong YIN ; Yujia ZHU ; Yong WANG ; Yijiao ZHAO
Chinese Journal of Stomatology 2024;59(12):1234-1239
		                        		
		                        			
		                        			Objective:To explore the impact of digital technology in constructing a three-dimensional (3D) symmetry reference plane (SRP) for esthetic restoration of anterior teeth and to evaluate its clinical applicability.Methods:A cross-sectional study was conducted from February to May 2024, involving 20 patients [11 males and 9 females, aged (36.8±11.4) years] who underwent anterior esthetic restorations at the Department of Stomatology, People′s Hospital of Ningxia Hui Autonomous Region. Symmetrical reference planes of patients′ 3D facial models were constructed using three different algorithms: weighted Procrustes analysis (WPA), Procrustes analysis (PA) based on the ontology-mirror correlation method, and iterative closest point (ICP). The SRP defined by an associate chief physician served as the control (true-value group). The angular errors between each algorithm group and the true-value group were compared. The optimal algorithm was selected and combined with a three-dimensional digital smile design (DSD) to create virtual patients, followed by designing anterior restorations. The visual analogue scale (VAS) was used by patients to score the aesthetic restoration results of the conventional design (control group) and the algorithm-based design (algorithm group).Results:The angular errors of the WPA, PA, and ICP groups were 1.43°±0.66°, 1.82°±0.88°, and 4.74°±2.03° respectively, with statistically significant differences among the groups ( F=41.10, P<0.001). Pairwise comparisons showed that the WPA group had significantly smaller angular errors compared to the PA and ICP groups ( P<0.05). The VAS scores for aesthetic restoration were significantly higher in the algorithm group (8.09±0.74) compared to the control group (6.30±1.38) ( t=-5.49, P<0.001). Conclusions:The SRP constructed using the WPA algorithm demonstrated minimal angular error when compared to the expert-defined SRP and is considered the optimal choice in clinical practice, yielding high patient satisfaction.
		                        		
		                        		
		                        		
		                        	
7.Clinical Study on the Analgesic Effect of Electroacupuncture Combined with Indomethacin Suppository in Transvaginal Ultra-sound-Guided Oocyte Retrieval
Yixin WANG ; Yanyun YIN ; Yujia KOU ; Yumeng DONG ; Yanni ZHANG ; Zhihao GAO ; Xiaocui LIU
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(6):628-632
		                        		
		                        			
		                        			OBJECTIVE To observe the auxiliary analgesic effect of electroacupuncture at Hegu and Neiguan combined with in-domethacin suppository in patients undergoing transvaginal ultrasound-guided oocyte retrieval(TUGOR and its effect on the outcome of in vitro fertilization(IVF.METHODS 64 IVF-ET patients undergoing TUGOR were randomly divided into a treatment group and a control group,32 cases in each group.One case dropped out of the treatment group during the treatment.The control group was given indomethacin suppository rectal administration,and the treatment group was given electroacupuncture at Hegu and Neiguan in addition to the treatment of the control group.The patients'tenderness threshold,VAS score,pain grade score,respiratory rate,and pulse rate were evaluated before and after TUGOR operation.The number of oocytes obtained,the rate of two pronuclei(2PN,embryo utiliza-tion rate,and high-quality embryo rate were evaluated after TUGOR operation.The adverse reactions of the two groups were monitored during and after operation.RESULTS After TUGOR operation,the VAS score and pain grade of the treatment group were signifi-cantly lower than those of the control group(P<0.01;the tenderness threshold of the two groups was significantly reduced after opera-tion(P<0.05,P<0.01,and the treatment group was better than the control group(P<0.05;the incidence of nausea during opera-tion,abdominal distension and nausea 48 h after operation in the treatment group were better than those in the control group(P<0.05;the high-quality embryo rate in the treatment group was better than that in the control group(P<0.05.CONCLUSION Electroacupuncture at Hegu and Neiguan combined with indomethacin suppository can effectively assist in analgesia,and can reduce the incidence of adverse reactions during and after TUGOR to varying degrees,and may have certain advantages in improving the rate of high-quality embryos.
		                        		
		                        		
		                        		
		                        	
8.Objective structured clinical examination-based annual assessment design and feedback
Chinese Journal of Medical Education Research 2024;23(5):613-618
		                        		
		                        			
		                        			Since 2004, Beijing Children's Hospital affiliated to Capital Medical University has applied objective structured clinical examination (OSCE) to comprehensively assess the post competency of pediatric residents during standardized training. While exploring a hierarchical and progressive training model for standardized residency training, according to the competency requirements for residents of different grades, our hospital has studied annual assessment strategies based on OSCE stations, and designed targeted annual assessment content and corresponding training courses, providing a reference for further improving the quality of training of pediatric residents.
		                        		
		                        		
		                        		
		                        	
9.Expert consensus on postoperative care of patients with a left ventricular assistant device
Nursing Professional Committee of the National Cardiovascular Disease Expert Committee ; Yan MA ; Rong WU ; Chen ZHANG ; Qingyin LI ; Yujia HUANG ; Mingjing ZHAO ; Qiang FU ; Yonggang LI ; Jiani WANG
Chinese Journal of Nursing 2024;59(14):1687-1690
		                        		
		                        			
		                        			Objective To standardize nursing management on postoperative patients with a left ventricular assist-ant device(LVAD).Methods The first draft of the Consensus was formed on the basis of literature review.2 rounds of expert consultations and a round of online meeting discussion were held for adjustments and modifications the draft of the Consensus.Results The recovery rate of the inquiry questionnaire was 93.75%.The authority coefficients of the 2 rounds of inquiry experts were 0.927 and 0.920.The concentration degree of expert opinions for each indicator was greater than 3.5 score,and the coefficient of variation was less than 0.25.The Kendall harmony coefficients for 2 rounds of correspondence were 0.402 and 0.407(P<0.01).The final Consensus formed through expert consultations and meetings includes 7 themes:hemodynamic monitoring,LVAD function monitoring,coagulation function monitoring,percutaneous cable and wound care,exercise rehabilitation care,health education and guidance,and pre-discharge assessment.Conclusion The Consensus is scientific,rigorous,and authoritative.The Consensus covers all aspects of postoperative care for patients with LVAD,and it will benefit to clinical practice.
		                        		
		                        		
		                        		
		                        	
10.Effect of Icariin on Peripheral Blood Dendritic Cells and Th17/Treg Balance in Myocardial Remodeling Model of Dahl Salt-sensitive Rats
Qian LI ; Yan ZHOU ; Yujia CHEN ; Wen LI ; Huanzhen WANG ; Liancheng GUAN ; Yunzhi CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):46-55
		                        		
		                        			
		                        			ObjectiveTo investigate the effect of icariin (ICA)-mediated vitamin D system on peripheral blood dendritic cells (DCs) and helper T cells 17 (Th17)/regulatory T cells (Treg) balance in myocardial remodeling model of Dahl salt-sensitive rats. MethodFifty SPF Dahl salt-sensitive rats were divided into model group, vitamin D group (3×10-5 mg·kg-1·d-1), and high-, medium-, and low-dose ICA groups (120, 60, 30 mg·kg-1·d-1), and 10 Dahl salt-resistant rats were used as normal group. The myocardial remodeling model was established by feeding rats with a high-salt diet containing 8% NaCl. After six weeks of modeling, the normal group and the model group were given an equal volume of ultrapure water by gavage, and other groups were continuously administrated for six weeks. Cardiac echocardiography, hematoxylin-eosin (HE) staining, and Masson staining were used to observe the pathological changes in cardiac structure and fibrosis. The levels of serum 25(OH)D3, B-type N-terminal pro-brain natriuretic peptide (NT-ProBNP), interleukin (IL)-17, transforming growth factor (TGF)-β1, IL-12, and IL-10 were detected by enzyme-linked immunosorbent assay (ELISA). The phenotype of peripheral blood DCs and the ratio of Th17/Treg cells of rats were detected by flow cytometry. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to detect the mRNA and protein expressions of vitamin D receptor (VDR),1α-hydroxylase (CYP27B1), and 24-hydroxylase (CYP24A1) in peripheral blood DCs of rats. ResultCompared with the control group, the rats in the model group had pathological changes such as disordered arrangement of myocardial cells and cytoplasmic hypertrophy and swelling. Myocardial collagen fibers proliferated significantly, and the arrangement of myocardial fibers was disordered. The levels of serum 25(OH)D3 and IL-10 were significantly decreased, and the levels of serum IL-17, TGF-β1, IL-6, IL-12, and NT-ProBNP were significantly increased (P<0.05). The costimulatory molecules CD40, CD80, CD86, and MHC-Ⅱ were highly expressed in the peripheral blood DCs, and the expression of CD11 and CD11b was lower (P<0.05). The proportion of Th17 cells in the peripheral blood was significantly increased, and the proportion of Treg cells was decreased. The ratio of Th17/Treg was increased (P<0.05). The mRNA and protein expressions of CYP24A1 in peripheral blood DCs increased, and the mRNA and protein expressions of CYP27B1 and VDR decreased (P<0.05). Compared with the model group, the arrangement of myocardial fibers in each drug administration group was relatively regular, and the swelling of myocardial cells was significantly reduced. The pathological morphology of myocardial tissue was improved to varying degrees. The pathological changes in myocardial tissue were improved and alleviated to varying degrees. The drug could reduce the serum levels of NT-ProBNP, IL-17, TGF-β1, IL-6, and IL-12 and increase the level of serum 25(OH)D3 and IL-10 (P<0.05). The expression of costimulatory molecules CD40, CD80, CD86, and MHC-Ⅱ in the peripheral blood DCs of rats was decreased, and the expression of CD11 and CD11b molecules was increased (P<0.05). The drug could reduce the proportion of Th17 cells in peripheral blood and the ratio of Th17/Treg cells and increase the proportion of Treg cells (P<0.05). It could decrease the mRNA and protein expressions of CYP24A1 in peripheral blood DCs of rats and elevate the mRNA and protein expression of VDR and CYP27B1 (P<0.05). ConclusionICA can regulate the phenotype of peripheral blood DCs and the ratio of Th17/Treg cells by regulating the vitamin D system and play a role in improving myocardial remodeling from the perspective of immune balance. 
		                        		
		                        		
		                        		
		                        	
            
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