1.Machine-learning-based models assist the prediction of pulmonary embolism in autoimmune diseases: A retrospective, multicenter study
Ziwei HU ; Yangyang HU ; Shuoqi ZHANG ; Li DONG ; Xiaoqi CHEN ; Huiqin YANG ; Linchong SU ; Xiaoqiang HOU ; Xia HUANG ; Xiaolan SHEN ; Cong YE ; Wei TU ; Yu CHEN ; Yuxue CHEN ; Shaozhe CAI ; Jixin ZHONG ; Lingli DONG
Chinese Medical Journal 2024;137(15):1811-1822
Background::Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD.Methods::In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort.Results::In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962-1.000 in the training cohort and 0.969-0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone.Conclusion::ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE.Trial Registration::Chictr.org.cn: ChiCTR2200059599.
2.Characterization and antibacterial properties of LysinB protein in bacteriophage TM4
Zhifen PAN ; Ziwei ZHOU ; Haiping XU ; Wei WANG
China Modern Doctor 2024;62(21):6-10,25
Objective To analyze the sequence of LysinB protein in bacteriophage TM4,express LysinB protein in E.coli and evaluate its bactericidal activity in vitro.Methods Bacteriophage TM4 LysinB gene was synthesized and the recombinant prokaryotic expression plasmid was constructed.The soluble protein was induced and purified.The biological characteristics of bacteriophage TM4 LysinB protein were analyzed by online software program.Mycobacterium smegmatis was cultured in 7H9 medium,and its bactericidal effect and stability were detected.Results The theoretical isoelectric point was 6.66,the instability index was 28.71,which was a stable and amphiphilic protein.In the secondary structure,The random coil,α-helix,β-fold and turn Angle accounted for 42.00%,40.25%,12.00%and 5.75%;In the tertiary structure,the content of random coil was high.The peptide composed of AA at positions 11 to 73 constituted the peptidoglycan binding domain.The regions of B cell epitopes and the strong binding peptides of T cell epitopes were predicted.LysinB protein has a significant ability to kill Mycobacterium smegmatis in vitro.PBST protein buffer with pH8.0 was beneficial to maintain the bactericidal effect of LysinB proteins during the experimental cycle.Conclusion This study expands the comprehensive understanding of the LysinB protein of mycobacterial phage TM4 lyase,and also provides reference for the development of stable storage of phage enzyme preparation and its clinical application.
3.Effects of Xin-Tong-Tai granule on expression of ox-LDL,ICAM-1 and VCAM-1 in ApoE-/-mice with atherosclerosis
Qinghua ZENG ; Ziwei YIN ; Aisi HUANG ; Jingyi CHEN ; Zhihua GUO ; Jiaming WEI
Chinese Journal of Pathophysiology 2024;40(6):989-996
AIM:To investigate the effects and mechanism of Xin-Tong-Tai granule on oxidized low-density li-poprotein(ox-LDL),intercellular adhesion molecule-1(ICAM-1)and vascular cell adhesion molecule-1(VCAM-1)in ApoE-/-mice with atherosclerosis(AS).METHODS:A total of 72 SPF-grade healthy male ApoE-/-mice aged 6~8 weeks were fed with high-fat diet for 12 weeks to replicate AS models,and 12 SPF-grade healthy male C57BL/6J wild mice were fed with ordinary diet as the control group.After the corresponding drugs were administered for 8 weeks,the body weight and general condition of mice in each group were observed.The serum levels of total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C)were detected by biochemi-cal kits.The pathological structures of aorta were observed by HE and oil red O staining.The levels of serum ox-LDL and aortic ICAM-1 and VCAM-1 were detected by ELISA.The protein levels of NADPH oxidase 4(NOX4),NOX subunit p22phox,inhibitor of κB kinase-α(IKK-α),IKK-β and nuclear factor-κB(NF-κB)in aorta were detected by Western blot.RESULTS:Compared with control group,the mice in model group showed increased body weight(P<0.05),dull and lo-cal shedding hair,slow grasping response,increased serum TC,TG and LDL-C levels,decreased serum HDL-C level(P<0.05),increased the levels of serum ox-LDL and aortic ICAM-1 and VCAM-1(P<0.05),and increased protein expres-sions of NOX4,p22phox,IKK-α,IKK-β and NF-κB in aorta(P<0.05).Compared with model group,the body weight of mice in each treatment group decreased(P<0.05),the hair loss and the response flexibility were also improved.The se-rum levels of TC,TG and LDL-C decreased and HDL-C increased(P<0.05).The levels of serum ox-LDL and aortic ICAM-1(except the low-dose Xin-Tong-Tai granule group)and VCAM-1 decreased(P<0.05).The protein levels of NOX4,p22phox,IKK-α,IKK-β and NF-κB in aorta decreased(P<0.05).HE and oil red O staining showed that typical AS plaques could be seen in blood vessels of the model group,and the red-stained areas were widely distributed.The above lesions were alleviated to different degrees in each treatment group compared with model group.CONCLUSION:Xin-Tong-Tai granule reduces the atherosclerotic plaque area of ApoE-/-mice induced by high-fat diet,decreased serum TC,TG and LDL-C levels,increased HDL-C level,decreased the levels of serum ox-LDL and aorta ICAM-1 and VCAM-1,and inhibited protein expression of NOX4,p22phox,IKK-α and IKK-β in the aorta,thereby attenuating AS.
4.Simultaneous detection of 34 emerging contaminants in tap water by HPLC-MS/MS and health risk assessment
Yixuan CAO ; Ziwei YUAN ; Xiaoxi MU ; Chenshan LV ; Haiyan CUI ; Tao WANG ; Zhiwen WEI ; Zhongbing CHEN ; Hongyan ZOU ; Keming YUN ; Meng HU
Chinese Journal of Forensic Medicine 2024;39(1):31-38
Objective To establish a simultaneous detection approach for 34 emerging contaminants(ECs)in tap water by liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).Human health risk assessment was performed according to the detection results from 43 tap water samples.Methods Tap water samples were concentrated and extracted by solid phase extraction,and then blown to near dry by nitrogen at 40℃.The sample extracts were dissolved in methanol-water solution(95:5,VN)to 0.5 mL for analyzing.Agilent Jet Stream Electrospray Ionization(AJS ESI)and the multiple reaction monitoring(MRM)mode were performed for MS to acquire the data of 34 ECs.A database including precursor ion,product ion and retention times was established accordingly.Results The average linear correlation coefficients(r)of 34 kinds of ECs was 0.995 9.The limits of detection were 0.01~0.60 ng/L and the recoveries were between 60.7%and 119.8%.The intra-group precisions were between 0.05%~9.89%and the intra-day precisions were between 0.20%~14.40%for the spiked samples.The method was applied to analyze 43 tap water samples and a total of 15 ECs were detected.According to the results,the detection rate of caffeine was the highest(84%),and the concentration range was ND~74.42 ng/L.Among all the ECs detected,1,2,3-benzotriazole had the highest concentration(ND~361.15 ng/L),where detection rate was 44%.Humans may be exposed to these ECs by drinking the tap water.The human health risk assessments of 12 kinds of ECs were carried out,however,the estimated risk was negligible(risk quotient<0.01).Conclusion The method is simple,highly sensitive and selective,and could meet the detection needs of ECs at trace level in tap water.There was no human health risk posed for ECs identified in 43 tap water samples analyzed by this method.
5.Expert Consensus of Multidisciplinary Diagnosis and Treatment for Paroxysmal Nocturnal Hemoglobinuria(2024)
Miao CHEN ; Chen YANG ; Ziwei LIU ; Wei CAO ; Bo ZHANG ; Xin LIU ; Jingnan LI ; Wei LIU ; Jie PAN ; Jian WANG ; Yuehong ZHENG ; Yuexin CHEN ; Fangda LI ; Shunda DU ; Cong NING ; Limeng CHEN ; Cai YUE ; Jun NI ; Min PENG ; Xiaoxiao GUO ; Tao WANG ; Hongjun LI ; Rongrong LI ; Tong WU ; Bing HAN ; Shuyang ZHANG ; MULTIDISCIPLINE COLLABORATION GROUP ON RARE DISEASE AT PEKING UNION MEDICAL COLLEGE HOSPITAL
Medical Journal of Peking Union Medical College Hospital 2024;15(5):1011-1028
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disease caused by abnormal expression of glycosylphosphatidylinositol (GPI) on the cell membrane due to mutations in the phosphatidylinositol glycan class A(PIGA) gene. It is commonly characterized by intravascular hemolysis, repeated thrombosis, and bone marrow failure, as well as multiple systemic involvement symptoms such as renal dysfunction, pulmonary hypertension, swallowing difficulties, chest pain, abdominal pain, and erectile dysfunction. Due to the rarity of PNH and its strong heterogeneity in clinical manifestations, multidisciplinary collaboration is often required for diagnosis and treatment. Peking Union Medical College Hospital, relying on the rare disease diagnosis and treatment platform, has invited multidisciplinary clinical experts to form a unified opinion on the diagnosis and treatment of PNH, and formulated the
6.2-APB inhibits H2O2-induced chondrocyte apoptosis through PKCα/HIF-1α signaling pathway
Ziwei OUYANG ; Lei DONG ; Yan WANG ; Yuanzhi CHENG ; Rendi ZHU ; Renpeng ZHOU ; Yingjie ZHAO ; Wei HU
Acta Universitatis Medicinalis Anhui 2024;59(7):1150-1156
Objective To explore the effect of 2-aminoethoxy-diphenyl borate(2-APB)on H2O2-induced chondro-cyte apoptosis and its mechanism.Methods The experiment was divided into control group,H2O2 group,2-APB group and H2O2+2-APB group.CCK-8 method was used to detect the cell viability of each group;The effect of 2-APB on the morphological changes of chondrocytes induced by H2O2 was observed under microscopy;TUNEL meth-od and flow cytometry were used to detect chondrocyte apoptosis;Flow cytometry was used to detect Lipid reactive oxygen species(ROS);Western blot was used to detect the protein expressions of Cleaved-PARP,p-PKCα and HIF-1α in H2O2-induced cells by 2-APB;Immunofluorescence was used to detect the fluorescent expression of HIF-1α in cells induced by H2O2 by PKCα inhibitor BIM-1.Results 2-APB inhibited H2O2-induced apoptosis in chon-drocytes,and the inhibitory effect was the most significant when the concentration of 2-APB was 100 pmol/L(F=235.80,P<0.01);22-APB could inhibit the positive rate of H2O2-induced apoptosis of chondrocytes(F=114.80,P<0.01)and the level of ROS(F=52.99,P<0.01).and inhibited the expression of Cleaved-PARP(F=10.10,P<0.05),p-PKCα(F=24.56,P<0.05)and HIF-1α proteins(F=6.85,P<0.05).The PKCα in-hibitor BIM-Ⅰ could inhibit the increase in HIF-1α fluorescence intensity caused by H2O2.Conclusion 2-APB can inhibit chondrocytes apoptosis induced by H2O2 through the PKCα/HIF-1α pathway and thus protect chondro-cytes.
7.A prediction model of live birth in patients undergoing frozen⁃thawed embryo transfer after TCRA
Ziwei Li ; Ying Wang ; Qiong Xing ; Zhiguo Zhang ; Yunxia Cao ; Zhaolian Wei ; Jianye Wang
Acta Universitatis Medicinalis Anhui 2023;58(11):1947-1951
Objective :
To develop a prediction model for live birth based on the basic characters of patients after
transcervical resection of adhesions (TCRA) undergoing frozen⁃thawed embryo transfer (F⁃ET) .
Methods :
A total of 491 cycles who went F ⁃ET after TCRA were included. The cycles were randomly divided into training (n = 347) and validation (n = 144) cohorts at 7 ∶ 3 ratio. Relevant factors of live birth were selected via logistic regression analysis based on the data from patients in the training cohort. Multivariate logistic regression analysis was used to establish a nomogram , and then this predict model was calibrated and verified.
Results :
Age , body mass index (BMI) , miscarriages and endometrial thickness were significantly related to the live birth. The statistical nomogram was built with the area under the ROC cu2rve for the training cohort was 0. 713 (95% CI: 0. 519 - 0. 815) , Hosmer⁃Lemeshow goodness of fit test were χ = 7. 062 , P = 0. 530 , and the slope of calibration curve was close to 1. AUC of validation cohort was 0. 609 (95% CI: 0. 660 - 0. 561) , presenting a well⁃pleasing goodness⁃of⁃fit and stability in this model.
Conclusion
Age , BMI , miscarriages and endometrial thickness can better predict the probability of live birth undergoing F ⁃ET after TCRA.
8.Progress in preparation and application of sodium alginate microspheres.
Xuanyu LIU ; Yuhui WANG ; Ziwei LIANG ; Xiaojie LIAN ; Di HUANG ; Yinchun HU ; Yan WEI
Journal of Biomedical Engineering 2023;40(4):792-798
Sodium alginate (SA) is a kind of natural polymer material extracted from kelp, which has excellent biocompatibility, non-toxicity, biodegradability and abundant storage capacity. The formation condition of sodium alginate gel is mild, effectively avoiding the inactivation of active substances. After a variety of preparation methods, sodium alginate microspheres are widely used in the fields of biomaterials and tissue engineering. This paper reviewed the common methods of preparing alginate microspheres, including extrusion, emulsification, electrostatic spraying, spray drying and coaxial airflow, and discussed their applications in biomedical fields such as bone repair, hemostasis and drug delivery.
Alginates
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Biocompatible Materials
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Drug Delivery Systems
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Microspheres
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Plastic Surgery Procedures
9.Comparison of Corneal Biomechanical Properties Based on Data from Uniaxial Tensile Test under Fast and Slow Loading
Di ZHANG ; Haixia ZHANG ; Zheng ZENG ; Ziwei YUAN ; Wei WANG ; Lin LI
Journal of Medical Biomechanics 2022;37(4):E669-E675
Objective To compare the corneal biomechanical parameters identified from uniaxial tensile test under fast and slow loading. Methods The stress-strain and stress relaxation data were obtained from uniaxial tensile tests on corneal strips from 15 healthy adult rabbits at average loading rate of 0.16 mm/s and 0.02 mm/s, respectively. A visco-hyperelastic model was applied to analyze the loading and unloading data from the fast tensile tests, where the model parameter set was denoted by Gvh. The first-order Ogden model and second-order Prony series model were used to fit stress-strain and stress relaxation data from the slow tensile tests, respectively, in which the model parameter set was denoted by Gvh. Correlation analysis was used to compare the correlation of parameters between Gvh and GOP. Results All the goodness-of-fits to the three data sets were greater than 0.95. There were significant differences in 5 (μ, A1, A2, τ1, τ2,) of the 6 parameters between Gvh and GOP (P<0.05), and the Ogden model parameters was positively correlated between the two groups. Conclusions There are differences in corneal biomechanical parameters identified by data from uniaxial tensile tests under fast and slow loading. The results provide a preliminary research basis for further exploring the use of clinical data to identify corneal biomechanical properties.
10.Serially evaluation of changes in myocardial perfusion, hibernation myocardium and left ventricular function in the development of chronic coronary artery occlusion by gated SPECT perfusion and gated PET imaging in pigs
Ying ZHANG ; Yi TIAN ; Tiantian MOU ; Mingkai YUN ; Ziwei ZHU ; Yao LU ; Jingjing MENG ; Wei DONG ; Xiang LI ; Xiaoli ZHANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2022;42(5):284-288
Objective:To serially characterize the myocardial perfusion, myocardial hibernation and left ventricular (LV) function as well as LV remodeling in progressive coronary artery stenosis in Chinese mini-pigs.Methods:In 8 Chinese mini-pigs (5 males, 3 females; age: 10 months), chronic progression of coronary stenosis and finally occlusion was established using Ameroid constrictor implantation at the 1 cm below the bifurcation of the first diagonal branch of the left anterior descending (LAD) artery. Serial gated 99Tc m-methoxyisobutylisonitrile(MIBI) SPECT/CT, gated 18F-FDG PET/CT imaging and coronary angiography (CAG) were performed before surgery and at the 1st, 4th and 8th week after surgery. Longitudinally, total perfusion defect (TPD), LV ejection fraction (LVEF), LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), summed motion score (SMS), summed thickening score (STS) and hibernating myocardium (HM) were analyzed. Repeated measures analysis of variance, Kruskal-Wallis rank sum test and Bonferroni correction method were used to analyze data. Results:One mini-pig died of infection after the Ameroid constrictor implantation. In the remaining 7 mini-pigs, TPD was progressively increased with time prolonged (0, 12.0%(0, 33.0%), (41.1±23.7)% and (49.3±24.5)%; H=17.03, P=0.001); Compared with HM before the surgery (100%), HM was gradually reduced from the 1st (21.0%(6.0%, 100%)) to the 4th (18.0%(3.0%, 33.0%)) week after surgery, and then increased to the 8th week after surgery ((23.0±15.4)%; H=13.09, P=0.004), but there was no significant difference between the 1st and 4th week, or between the 4th and 8th week after surgery (both P>0.05 (Bonferroni correction method)). Accordingly, LVEF gradually decreased ((73.7±8.4)%, (63.7±19.1)%, (53.7±14.6)% and (49.9±15.4)%; F=6.22, P=0.004). LVEDV (9.0(6.0, 21.0), (31.4±16.3), (32.9±17.4) and (36.4±17.5) ml; H=8.58, P=0.035)and LVESV ((3.8±3.2), (15.9±15.3), 12.0(10.0, 17.0)and (19.3±10.9) ml; H=10.51, P=0.015) gradually increased. SMS and STS continuously increased as well ( H values: 16.49, 13.33, P values: 0.001, 0.004). Conclusions:With the progression of coronary artery stenosis to occlusion, myocardial perfusion is gradually decreased, while the global and regional LV function, LV remodeling are gradually aggravated, and HM is gradually reduced. After the chronic coronary artery occlusion, myocardial perfusion has a trend to be improved and HM is gradually recovered.


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