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.Concordance and pathogenicity of copy number variants detected by non-invasive prenatal screening in 38,611 pregnant women without fetal structural abnormalities.
Yunyun LIU ; Jing WANG ; Ling WANG ; Lin CHEN ; Dan XIE ; Li WANG ; Sha LIU ; Jianlong LIU ; Ting BAI ; Xiaosha JING ; Cechuan DENG ; Tianyu XIA ; Jing CHENG ; Lingling XING ; Xiang WEI ; Yuan LUO ; Quanfang ZHOU ; Ling LIU ; Qian ZHU ; Hongqian LIU
Chinese Medical Journal 2025;138(4):499-501
3.Analgesic effects and mechanisms of Hegu acupoint catgut embedding in a rat model of labor
Zijing ZHANG ; Minli HUANG ; Hongfei DAI ; Jiaxin LI ; Zuen LIN ; Feng SUN ; Ruiping PANG ; Lingling WU
Chinese Journal of Pathophysiology 2024;40(10):1943-1949
AIM:This study aimed to observe the analgesic effects of Hegu acupoint catgut embedding in a rat model of labor and investigate its influence on biomarkers such as calcitonin gene-related peptide(CGRP)signals at the Hegu acupoint.METHODS:Thirty-six pregnant rats were randomly divided into three groups:control group,Hegu acu-puncture group,and Hegu catgut embedding group.Pain threshold changes were assessed using the tail immersion test and paw withdrawal thermal latency at four time points:pre-induction,before the onset of labor,at the onset of labor,and at the mid-stage of labor.Tissue samples from the Hegu acupoint were collected at the mid-stage of labor to detect the ex-pression of CGRP,substance P(SP),and mast cells using immunofluorescence.The concentrations of ATP and ade-nosine were measured using ELISA.RESULTS:Before labor induction,there was no significant difference in tail immer-sion test and paw withdrawal thermal latency among the three groups(P>0.05).Before the onset of labor,both the acu-puncture and catgut embedding groups exhibited significantly higher tail-flick times and paw withdrawal latencies com-pared to the control group(P<0.05).At labor initiation and mid-labor,the catgut embedding group had significantly higher tail-flick times and paw withdrawal latencies compared to both the control and acupuncture groups(P<0.05).During mid-labor,the expression of CGRP,SP,mast cells,ATP,and adenosine concentrations in the catgut embedding group was significantly higher than that in the control and acupuncture groups(P<0.05),with co-expression of CGRP,SP,and mast cells observed.CONCLUSION:Hegu acupoint catgut embedding effectively alleviates labor pain,and its mechanism may involve increased local expression of CGRP and SP,promoting mast cell degranulation,and increasing ATP release and its conversion to adenosine.
4.A multicenter prospective study on early identification of refractory Mycoplasma pneumoniae pneumonia in children
Dan XU ; Ailian ZHANG ; Jishan ZHENG ; Mingwei YE ; Fan LI ; Gencai QIAN ; Hongbo SHI ; Xiaohong JIN ; Lieping HUANG ; Jiangang MEI ; Guohua MEI ; Zhen XU ; Hong FU ; Jianjun LIN ; Hongzhou YE ; Yan ZHENG ; Lingling HUA ; Min YANG ; Jiangmin TONG ; Lingling CHEN ; Yuanyuan ZHANG ; Dehua YANG ; Yunlian ZHOU ; Huiwen LI ; Yinle LAN ; Yulan XU ; Jinyan FENG ; Xing CHEN ; Min GONG ; Zhimin CHEN ; Yingshuo WANG
Chinese Journal of Pediatrics 2024;62(4):317-322
Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.
5.Effects and mechanisms of 2.5T terahertz radiation exposure on testis injury in mice
Qinlong MA ; Min LIN ; Peng GAO ; Lingling YANG ; Yonghui LU ; Yanwen ZHANG ; Zhengping YU ; Chunhai CHEN
Journal of Army Medical University 2024;46(19):2197-2207
Objective To investigate the effects of terahertz(THz)radiation on mouse testicular tissue and its potential molecular mechanisms.Methods A total of 125 male C57BL/6J mice(6~8 weeks old)were randomly divided into control group and low-,medium-and high-radiation power groups.The mice of the latter 3 groups were exposed to THz radiation at a frequency of 2.5 T,with an average power density of 38,115,or 318 mW/cm2,for 5 or 10 min.The detection time was immediately or 24 h after exposure.HE staining was used to observe pathological damage.ELISA was employed to detect the expression of inflammatory factors in testicular tissue.RNA-seq was utilized to detect the global changes of gene expression.The differentially expressed genes(DEGs)were screened and bioinformatics was used to cluster them.The screened genes were further analyzed with RT-qPCR to determine the time-dependent and dose-dependent relationships of the expression with THz exposure.Finally,sperm quality was evaluated morphologically using a microscope.Results Three doses of THz radiation exposure did not cause significant pathological damages to mouse testicular tissue.TNF-α expression was increased immediately after exposure at average power density of 115 mW/cm2(P<0.01),and the expression of IL-1β and TNF-α were both increased when the dose reached 318 mW/cm2(P<0.01).However,all the 3 factors returned to normal levels in 24 h after exposure.RNA-seq results showed that THz radiation exposure caused abnormal expression of 56 genes.Cluster analysis indicated that these DEGs were mainly enriched in immune and inflammatory responses,enzyme activity,sperm development and capacitation functions.Then for 5 selected key genes,Crisp1,Adam7,Ltf,Rnase9,and Bsph1,the expression of Crisp1 and Rnase9 was decreased immediately after exposure to 115 mW/cm2 THz radiation,the dose of 318 mW/cm2 resulted in obvious changes in the expression of the 5 genes(P<0.05),and their expression returned to normal levels in 24 h after exposure.Morphological observation displayed that exposure to all the 3 doses of THz had no influence on sperm quality.Conclusion THz radiation exposure causes temporary inflammatory response in testicular tissue and abnormal expression of sperm functions-related genes.However,these changes return to normal 24 h after exposure,and additionally,do not impair sperm quality.
6.Efficacy analysis of blood inflammation and liver function indexes in ICP diagnosis and delivery mode prediction
Yuanyan ZHANG ; Lingling ZHANG ; Lin KONG ; Yanting CHEN ; Qiyun HUANG ; Lichun TANG
Chongqing Medicine 2024;53(4):522-527
Objective To observe the changes of laboratory blood indexes in patients with intrahepatic cholestasis of pregnancy(ICP),and analyze the value of blood inflammation indexes and liver function indexes in the diagnosis of ICP and the prediction of delivery mode.Methods A total of 251 patients diagnosed with ICP in this hospital from January 2021 to December 2022 were selected as the ICP group,and another 200 healthy pregnant women were selected as the control group.The patients with ICP were further divided into the severe ICP group(n=47)and the mild ICP group(n=204),the vaginal delivery group(n=113)and the cesarean section group(n=138)according to the severity of ICP and delivery mode.Mann-Whitney U test was used for comparison of parameters between groups,and Spearman method was used for correlation analy-sis.Receiver operating characteristic(ROC)curves were used to evaluate the efficacy of laboratory indicators in diagnosing ICP and predicting delivery mode.Results Neutrophil/lymphocyte ratio(NLR)[6.01(4.45,8.37)vs.3.36(4.12,3.51)]and aspartate transaminase(AST)level[20.00(16.00,33.00)U/L vs.15.00(13.00,18.00)U/L]in the ICP group were significantly higher than those in the control group(P<0.05),and NLR in the severe ICP group was significantly higher than that in the mild ICP group[4.93(3.87,7.35)vs.4.14(3.12,5.17),P<0.05].Correlation analysis showed that NLR was positively correlated with AST level(r=0.279,P<0.001)and ICP severity(r=0.139,P=0.028)in patients with ICP.The area under ROC curve(AUC)of NLR combined with AST for ICP diagnosis was 0.882(95%CI:0.851-0.913).In ad-dition,cholinesterase(CHE)[6 020.00(5 499.50,6 703.50)U/L vs.5 341.50(4 651.75,6 259.25)U/L]and prealbumin(PA)[199.00(177.71,225.20)mg/Lvs.169.17(139.18,204.40)mg/L]levels in the va-ginal delivery group were significantly higher than those in the cesarean section group(P<0.05),and the AUC of CHE combined with PA for predicting vaginal delivery in ICP patients was 0.727(95%CI:0.664-0.789).Conclusion NLR and AST have potential value in the diagnosis of ICP,and CHE and PA have poten-tial value in predicting delivery mode of ICP patients.
7.Hypofractionated radiotherapy in 10 fractions following modified radical mastectomy for breast cancer: a phase Ⅱ study
Huayong JIANG ; Dawei ZHAO ; Yanrong LUO ; Lingling MENG ; Xiangkun DAI ; Wei YU ; Lin MA
Chinese Journal of Radiological Medicine and Protection 2024;44(11):931-935
Objective:To evaluate the safety and clinical efficacy of hypofractionated radiotherapy (HFRT) at 36.5 Gy in 10 fractions for the chest wall and reginal lymph nodes following modified radical mastectomy for breast cancer.Methods:This was a prospective, single-arm, phase Ⅱ clinical study. A total of 85 patients who received HFRT at 36.5 Gy in 10 fractions to the chest wall ± supraclavicular region following modified radical mastectomy for locally advanced breast cancer from March 2014 to December 2015 were included. The primary endpoint was radiotherapy toxicities. The secondary endpoints were locoregional failure-free survival (LRFFS), disease-free survival (DFS), and overall survival (OS).Results:The median follow-up period was 98 (94.0-109.0) months. Radiotherapy toxicities were mild. The incidence rates of grade 1 acute cutaneous and pulmonary toxicities were 52.9% and 40%, and those of grade 1 late cutaneous, pulmonary, and cardiac toxicities and upper extremity edema were 10.6%, 29.4%, 2.4%, and 21.2%, respectively. Only 1 (1.2%) patient suffered from grade 2 radiation-induced brachial plexus injury. Of the 85 patients, one patient had regional recurrence (supraclavicular lymph nodes), six patients had distant metastasis, and six patients died of breast cancer. The 9-year LRFFS, DFS, and OS were 97.7%, 91.8%, and 92.8%, respectively.Conclusions:HFRT at 36.5 Gy in 10 fractions following modified radical mastectomy for breast cancer is associated with mild toxicities. A phase Ⅲ study is necessary for validating HFRT's clinical efficacy.
8.The concept of Health-Literate Schools and implications for China
TONG Yingge ; WEI Yeling ; QIAN Jinwei ; LI Yixuan ; LIN Ying ; WANG Miaoling ; LUO Lingling
Journal of Preventive Medicine 2024;36(3):264-267
Abstract
Enhancing the health literacy of the entire population is a prerequisite for improving the health of the entire population, and since the health attitudes and behaviors formed during childhood and adolescence have a profound impact on the health patterns of adulthood, the enhancement of health literacy of children and adolescents is of particular importance. As the main place for children and adolescents to receive education, schools should better fulfil the function of education and promotion of health literacy. China has been carrying out the pilot and promotion of health promoting schools (HPS) since 1995, and is currently in the stage of comprehensive improvement of HPS construction. This paper introduces the background and characteristics of Health-Literate Schools (HeLit-Schools) in foreign countries and compares them with HPS in China, drawing on the advantages of HeLit-Schools to provide a new idea and a new way of thinking for the construction of HPS in China and for the practice of the "Healthy China Initiative".
9.Preparation of heparinized acellular vascular scaffold and hemocompatibility evaluation
Xiafei LI ; Lingling ZHAO ; Feng LIANG ; Xuewei ZHANG ; Jinjin ZHANG ; Fei LIN ; Tuo YANG ; Liang ZHAO
Chinese Journal of Tissue Engineering Research 2024;28(17):2631-2636
BACKGROUND:Acellular vascular scaffolds can mimic the microstructure and function of native blood vessels,but some extracellular matrix loss occurs during their preparation,which affects their hemocompatibility.Therefore,it is necessary to modify them to improve their hemocompatibility. OBJECTIVE:To assess the hemocompatibility of acellular vascular scaffold prepared by Triton-x100/heparin sodium treatment. METHODS:The abdominal aorta was taken from SD rats and randomly divided into control and experimental groups.The control group was treated with Triton-x100 for 48 hours.The experimental group was treated with Triton-x100 for 48 hours and then treated with heparin sodium.The morphology and hydrophilicity of the two groups of acellular vascular scaffolds were detected.The hemocompatibility of the two groups of acellular vascular scaffold was evaluated by recalcification coagulation time test,platelet adhesion test,dynamic coagulation time test,hemolysis test,and complement activation test. RESULTS AND CONCLUSION:(1)Scanning electron microscopy showed that the surface of the two groups of vascular scaffolds was relatively intact,and a large number of fiber filaments appeared on the surface of the scaffolds after decellularity treatment,and the surface microstructure changed significantly.The water contact angle of the two groups of vascular scaffolds was smaller than that of natural vessels(P<0.000 1).There was no significant difference in water contact angle between the two groups(P>0.05).(2)The coagulation time of vascular scaffold was longer in the experimental group than in the control group(P<0.05).The number of platelets attached to the scaffold membrane was less in the experimental group than that in the control group(P<0.000 1).The coagulation index was greater in the experimental group than that in the control group(P<0.01),and the complement level was lower in the experimental group than that in the control group(P<0.001).The hemolysis rate of the two groups was lower than 5%of the national standard.(3)To conclude,acellular scaffold treated with Triton-x100/heparin sodium has excellent hemocompatibility.
10.A Potential Novel Targeted Drug for the Treatment of Pulmonary Arterial Hypertension:Imatinib
Shanshan XIE ; Ye LI ; Lingling YU ; Jinjin WAN ; Zhiying HUANG ; Huanyu LIN ; Weifang ZHANG
Herald of Medicine 2024;43(2):262-266
Pulmonary hypertension has a high mortality rate,and although targeted therapy is available,it is still incurable,and the long-term prognosis for patients is poor.As a tyrosine kinase inhibitor,imatinib was approved for marketing in China in 2002 for the treatment of chronic myelogenous leukemia and other tumor diseases.In addition to the antitumor effects,imatinib was found to improve hemodynamics and exercise tolerance in patients with severe pulmonary arterial hypertension,but the safety was suboptimal.With the emergence of new formulations of imatinib targeted at the lungs,it is expected to become a new targeted drug for pulmonary arterial hypertension.


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