Objective To observe the value of 3D Res2Net deep learning model for predicting volume doubling time(VDT)of solid pulmonary nodule.Methods Chest CT data of 734 patients with solid pulmonary nodules were retrospectively analyzed.The patients were divided into progressive group(n=218)and non-progressive group(n=516)according to whether lung nodule volume increased by ≥25％during follow-up or not,also assigned into training set(n=515)and validation set(n=219)at a ratio of 7∶3.Then a clinical model was constructed based on clinical factors being significantly different between groups,CT features model was constructed based on features of nodules on 2D CT images using convolutional neural network,and 3D Res2Net model was constructed based on Res2Net network using 3D CT images as input.Receiver operating characteristic curve was drawn,and the area under the curve(AUC)was calculated.Taken actual VDT as gold standard,the efficacy of the above models for predicting solid pulmonary nodule'VDT≤400 days were evaluated.Results No significant difference of predicting efficacy for solid pulmonary nodule'VDT≤400 days was found among clinical model,CT feature model and 3D Res2Net model,the AUC of which was 0.689,0.698 and 0.734 in training set,0.692,0.714 and 0.721 in validation set,respectively.3D Res2Net model needed 5-7 s to predict VDT of solid pulmonary nodules,with an average time of(5.92±1.08)s.Conclusion 3D Res2Net model could be used to predict VDT of solid pulmonary nodules,which might obviously reduce manual interpreting time.

Objective:To explore the effect of Notch1 signaling on regulatory T cells and its roles in vascular damage in patients with Kawasaki disease (KD).Methods:A total of 42 children with KD were enrolled in the present study from March 2019 to June 2020, as 32 age-matched healthy children were recruited as control. The proportions of CD4 +CD25 hiFoxp 3+ regulatory T cells (Treg) and expressions of transcription factor forkhead box protein 3 (Foxp3), cytotoxic T lymphocyte associated antigen-4 (CTLA4), glucocorticoid-induced tumor necrosis factor receptor (GITR), and Notch1 protein were evaluated by flow cytometry. Chromatin immunoprecipitation was conducted to detect acetylation level of histone H4 (H4Ac) associated with the promoter of Foxp3 gene and its binding abilities of Notch1 intracellular domain 1 (NICD1), recombination signal binding protein for immunoglobulin kappa J region (RBP-J) and p300 in CD4 + T cells. Transcription levels of Foxp3, presenilin 1 (PSEN1), mastermind like transcriptional coactivator 1 (MAML1), and RBP-J in CD4 + T cells were determined by real-time polymerase chain reaction (PCR). Concentrations of interleukin (IL)-10 and transforming growth factor-β (TGF-β) in plasma and culture supernatant stimulated with Jagged1 were measured by enzyme linked immunosorbent assay. Independent-sample t-test, Pearson correlation analysis was used as the statistical method in this study. Results:① The frequencies of Treg in acute KD patients decreased significantly [(4.3±1.5)% vs (7.9±2.9)%; t=6.41, P<0.001], as protein levels of Foxp3, CTLA4 and GITR and concentrations of IL-10 and TGF-β in plasma reduced remarkably in acute KD patients ( t=6.87, P<0.001; t=4.26, P<0.001; t=7.88, P<0.001; t=8.42, P<0.001; t=13.01, P<0.001). All parameters afore-mentioned in patients combined with coronary artery lesions (CAL) were lower than those of patients without coronary artery lesions (NCAL) ( t=5.83, P<0.001; t=3.83, P<0.001; t=3.28, P=0.002; t=5.05, P<0.001; t=5.96, P<0.001; t=5.17, P<0.001), and increased after therapy ( t=7.13, P<0.001; t=6.10, P<0.001; t=4.31, P<0.001; t=6.55, P<0.001; t=7.40, P<0.001; t=7.84, P<0.001). ② H4Ac associated with promoter of Foxp3 gene and the binding abilities of NICD1 and p300 in acute KD patients were lower than those of the controls ( t=10.25, P<0.001; t=6.93, P<0.001; t=6.75, P<0.001), and increased remarkably after therapy ( t=7.72, P<0.001; t=4.16, P<0.001; t=5.76, P<0.001). Meanwhile, the three items in CAL group were found to be less than those of NCAL group ( t=6.08, P<0.001; t=2.66, P=0.011; t=6.02, P<0.001). Pearson correlation analysis showed a positive correlation between H4Ac associated with Foxp3 promoter and its mRNA level in acute KD patients ( r=0.47, P<0.001). No statistical significant difference about the binding ability of RBP-J with Foxp3 promoter were found among the groups ( t=0.57, P>0.05; t=0.61, P>0.05; t=1.20, P>0.05). ③ Protein level of Notch1 and the expressions of PSEN1, MAML1 and RBP-J mRNA in CD4 + T cells from acute KD patients were down-regulated remarkably ( t=5.28, P<0.001; t=6.31, P<0.001; t=11.78, P<0.001; t=8.06, P<0.001), and restored after therapy ( t=4.77, P<0.001; t=6.43, P<0.001; t=11.95, P<0.001; t=7.79, P<0.001). In parallel, the four indexes aforementioned of CAL group were lower than those of NCAL group ( t=3.16, P=0.003; t=4.13, P<0.001; t=5.42, P<0.001; t=4.05, P<0.001). Upon rhJagged1 stimulation for 48 hours, H4Ac level of Foxp3 promoter and its binding abilities with NICD1 and p300 in CD4 + T cells in KD patients and control group was significantly higher than those of untreated group [(KD: t=15.36, P<0.001; t=7.25, P<0.001; t=14.29, P<0.001), (Ctrl: t=7.87, P<0.001; t=5.71, P<0.001; t=8.74, P<0.001)], as the binding ability of RBP-J with Foxp3 promoter increased slightly without statistically significant difference (KD: t=1.11, P>0.05; Ctrl: t=1.37, P>0.05). Simultaneously, H4Ac level of Foxp3 promoter and its binding abilities with NICD1 and p300 in KD group were still lower than those of the control group after stimulation ( t=3.86, P<0.001; t=3.42, P=0.001; t=2.85, P=0.006). ④ After incubation of PBMC from heathy children with KD serum, the proportion of Treg cells, protein level of Foxp3 and expressions of Notch1 and RBP-J in CD4 + T cells in the group treated with IVIG increased significantly compared with the untreated group ( t=7.10, P<0.001; t=10.16, P<0.001; t=8.06, P<0.001; t=9.77, P<0.001), as well as H4Ac level of Foxp3 promoter and its binding abilities with NICD1 in the group treat with IVIG were also higher than the latter ( t=7.24, P<0.001; t=8.24, P<0.001). Conclusion:Insufficiency and impaired function of Treg caused by aberrant Notch1 signaling may be the important factor contributing to immune dysfunction and vascular damage in KD.

Objective:To compare the clinical effects of hip arthroplasty through direct anterior approach (DAA) in lateral decubitus in the treatment of hip osteoarthritis caused by Kaschin-Beck disease and congenital acetabular dysplasia.Methods:The prospective study method was used to select the patients who needed hip arthroplasty in the Fourth Department of Orthopedics, the Second Affiliated Hospital of Harbin Medical University from January 2015 to December 2019. All of them were operated with lateral decubitus DAA. According to the inclusion criteria, they were divided into Kacshin-Beck disease hip osteoarthritis group (group A) and congenital acetabular dysplasia hip osteoarthritis group (group B). Hip Harris score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, visual analogue scale (VAS) score were conducted, and hip abduction angle and flexion angle were measured before surgery, 3, 14 days and 1, 3, and 12 months after surgery.Results:Nineteen and twenty-two patients were included in group A and group B, respectively. All patients successfully completed the surgery. There was no significant difference in Harris score between the two groups before surgery, 3, 14 days, and 1, 12 months after surgery ( P > 0.05). There were no significant differences in WOMAC score, VAS score, hip abduction angle and hip flexion angle between the two groups before surgery and each time point after surgery ( P > 0.05). In the same group, there were significant differences in Harris score, WOMAC score, VAS score, hip abduction angle and hip flexion angle at different time points ( P < 0.001). All postoperative indicators were significantly improved compared with those before surgery. Conclusions:There is no significant difference in the clinical effects of hip arthroplasty through lateral decubitus DAA in the treatment of hip osteoarthritis caused by Kaschin-Beck disease and congenital acetabular dysplasia. This surgical method has good therapeutic effect on both types of hip osteoarthritis.

Objective:To investigate the changes and significance of granulocyte-like myeloid-derived suppressor cells (G-MDSC) in the acute phage of Kawasaki disease (KD).Methods:Forty-two children with acute KD were enrolled in the present study and 32 age-matched healthy children were selected as control group. The proportion of HLA-DR -CD11b + CD33 + CD14 -CD15 + G-MDSC, the concentration of reactive oxygen species (ROS) and the expression of arginase-1 (Arg-1), programmed death-ligand 1 (PD-L1), cytotoxic T lymphocyte associated protein 4 (CTLA4), glycoprotein 130 (gp130) and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) at protein level were detected by flow cytometry. Quantitative real-time PCR was used to measure the expression of inducible nitric oxide synthase (iNOS), interferon regulatory factor 8 (IRF-8), IL-6 receptor α subunit (IL-6Rα), granulocyte colony-stimulating factor receptor (G-CSFR), CCAAT/enhancer binding protein β (C/EBPβ), suppressor of cytokine signaling 1 (SOCS1) and SOCS3 at mRNA level in G-MDSC. Chromatin immunoprecipitation was performed to detect the acetylation of histone H3 at the promoters of SOCS1 and SOCS3 genes. Plasma concentrations of IL-6 and granulocyte colony-stimulating factor (G-CSF) and protein levels of IL-10, transforming growth factor-β (TGF-β) and nitric oxide (NO) in the culture supernatant of G-MDSC stimulated with LPS were measured by ELISA. Results:(1) Compared with the control group, the proportion of HLA-DR -CD11b + CD33 + CD14 -CD15 + G-MDSC as well as the concentration of ROS and the expression of inhibitory molecules (Arg-1, PD-L1 and CTLA4) in G-MDSC increased significantly in patients with acute KD ( P<0.05). Moreover, the concentrations of IL-10 and TGF-β in culture supernatant of G-MDSC were also higher than those of the control group after stimulation with lipopolysaccharide for 48 h ( P<0.05). All of the seven afore-mentioned indexes in KD patients with coronary artery lesion (CAL group ) were lower than those in patients without coronary artery lesion (NCAL group) ( P<0.05), and restored to some extent after IVIG therapy ( P<0.05). There were no statistical differences in iNOS expression or NO concentration in culture supernatant of G-MDSC among different groups ( P<0.05). (2) Plasma concentrations of IL-6 and G-CSF, and the expression of IL-6Rα, gp130, G-CSFR, pSTAT3 and C/EBPβ increased remarkably during acute phase of KD ( P<0.05). The expression of IRF-8 at transcription level in patients with acute KD was found to be lower than that of healthy controls ( P<0.05), and restored significantly after IVIG therapy ( P<0.05). Moreover, the plasma concentrations of IL-6 and G-CSF and the expression of IL-6Rα, gp130, G-CSFR and IRF-8 in the CAL group were higher than those in the NCAL group ( P<0.05), while the expression of pSTAT3 and C/EBPβ was lower in the CAL group ( P<0.05), which were restored by IVIG therapy ( P<0.05). (3) In patients with acute KD, the expression of SOCS1 and SOCS3 at mRNA level and histone acetylation at the promoters of SOCS1 and SOCS3 genes were reduced significantly in comparison with those in healthy controls ( P<0.05) , but were increased remarkably after IVIG treatment( P<0.05). The four indexes were higher in the CAL group than in the NCAL group ( P<0.05). Pearson correlation analysis showed the expression of SOCS1 and SOCS3 was negatively correlated with the protein level of pSTAT3 in G-MDSC of patients with acute KD ( r=-0.46 and -0.32, P<0.05). Conclusions:Changes in the number and function of G-MDSC caused by aberrant histone acetylation at SOCS1 and SOCS3 genes might contribute to the immune dysfunction and vascular damage in patients with KD.

Objective:To investigate the changes of monocytic myeloid-derived suppressor cells (M-MDSC) in children with acute Kawasaki disease (KD) and its roles in the immunological pathogenesis of KD.Methods:A total of 38 children with acute KD were enrolled in the present study and 32 age-matched healthy children were selected as control group. The proportions of HLA-DR -CD11b + CD33 + CD15 -CD14 + M-MDSC and CD4 + CD25 + CD127 - regulatory T cells (Treg) in peripheral blood, concentrations of reactive oxygen species (ROS) and expression of arginase-1 (Arg-1), CD39, CD73, CD40, CD40L and CCR5 at protein levels were detected by flow cytometry. Quantitative real-time PCR was used to evaluate the transcription levels of inducible nitric oxide synthase (iNOS) in M-MDSC and the transcription levels of cytotoxic T-lymphocyte associated antigen 4 (CTLA4) and lymphocyte-activation gene 3 (LAG3) in Treg. Concentrations of NO, CCL3, CCL4, CCL5, IL-10 and TGF-β in the supernatants of cell culture were measured by ELISA. Results:(1) The proportion of HLA-DR -CD11b + CD33 + CD15 -CD14 + M-MDSC, the concentration of intracellular ROS and the expression of iNOS, CD39 and CD73 in M-MDSC decreased significantly in patients with acute KD as compared with those in the control group ( P<0.05), and the concentrations of NO, IL-10 and TGF-β in culture supernatant of M-MDSC were lower than those in the control group upon lipopolysaccharide (LPS) stimulation for 48 h ( P<0.05). All of the aforementioned indexes restored to some extent after intravenous immunoglobulin (IVIG) therapy ( P<0.05). No statistical differences were found in Arg-1 expression between healthy controls and patients with KD before or after IVIG therapy ( P<0.05). (2) CD40 expression on M-MDSC was significantly lower in the acute KD group than in the control group ( P<0.05). The concentrations of CCL3, CCL4 and CCL5 in the culture supernatants of M-MDSC were lower in the acute KD group than in the control group after LPS stimulation ( P<0.05). With IVIG treatment, all of the indexes were up-regulated significantly ( P<0.05), although CD40 expression was still lower in the acute KD group than in the control group ( P<0.05). (3) The proportion of CD4 + CD25 + CD127 -Treg and the expression of CTLA4, LAG3, CD40L and CCR5 reduced significantly in patients with acute KD as compared those in healthy controls ( P<0.05), and all increased remarkably after IVIG therapy ( P<0.05). Pearson correlation analysis showed a positive correlation between the proportions of M-MDSC and Treg in patients with acute KD ( r=0.58, P<0.05). Conclusions:Insufficiency and impaired function of M-MDSC might be a major cause of immune dysfunction in patients with acute KD.

Objective To analyze the risk factors of in-hospital mortality in patients with intracerebral hemorrhage (ICH) in the intensive care unit.Methods Patients with intracerebral hemorrhage were retrospectively collected from January 2013 to January 2018 in the Department of Intensive Care Unit,Zhongnan Hospital of Wuhan University.Patients were excluded aged less than 18 years,pregnant women,the onset time of more than 7 days,the length of hospital stay of less than 48 hours,lack of renal function outcomes within 24 hours after admission,the glomerular filtration rate (eGFR) of lower than 15 mL/(min.1.73 m2),the history of chronic kidney disease,regular dialysis and renal transplantation,and incomplete data.Clinical data were collected from baseline characteristics,past history,and laboratory examination.The included patients were divided into the in-hospital non-survival group and the survival group.SPSS 20.0 software as used for statistical analysis,the binary Logistic regression analysis was performed to evaluate risk factors of in-hospital mortality with intracerebral hemorrhage,the prognosis was assessed by receiver operating characteristic (ROC) curve and survival curve (Kaplan-Meier).A P＜0.05 was considered statistically significant.Results In this single-center retrospective study,a total of 300 patients were enrolled,including 96 patients in the hospital nonsurvival group and 204 patients in the survival group.The incidence of in-hospital death in patients with intracerebral hemorrhage in ICU was 32％.Multivariate analysis demonstrated that the risk factors of inhospital mortality were lower GCS score (OR=0.629,95％CI:0.523-0.757,P＜0.01),higher APACHE Ⅱ score (OR=1.590,95％CI:1.369-1.847,P＜0.01),elevated leukocytes (OR=1.082,95％CI:1.028-1.139,P=0.002) and the incidence of acute kidney injury (AKI) (OR=6.978,95％CI:3.381-14.405,P＜0.01).The ROC curve demonstrated that the area under curve (AUC) of APACHE Ⅱ score was the largest with a sensitivity and specificity of 73.96％ and 75.98％,respectively,which can better predict the mortality of patients with cerebral hemorrhage.Kaplan-Meier survival curve showed that in-hospital survival rate of non-AKI patients were higher than that of AKI patients (P＜0.01).Conclusions Lower GCS score,higher APACHE Ⅱ score,elevated white blood cells and AKI are risk factors for predicting in-hospital mortality in patients with intracerebral hemorrhage in the ICU.Therefore,early identification and treatment should be adopted in these high-risk populations.

Objective: To investigate the prognostic value of radiomics analysis in predicting axillary lymph nodes (ALN) metastasis of breast cancer based on dynamic contrast-enhanced MR imaging (DCE-MRI). Methods: One hundred and ninety-six patients with suspected breast cancer were prospectively collected for dynamic breast DCE-MRI. Enhanced MR imaging data of 72 axillary lymph nodes were evaluated separately by a chief radiologist and a resident, and the consistency analysis was performed. Lymph nodes were dichotomized according to the pathology results derived from operation or biopsy under real-time virtual sonography based on MRI data. Clinical and imaging data were also divided into corresponding groups. (Imaging) Data from both groups were respectively classified as training set and testing set by stratified sampling in proportion with 3∶1. AK software was applied to extract 6 major categories of 385 features (including histogram, morphology, texture parameters, gray level co-occurrence matrix, run-length matrix and grey level zone size matrix from imaging), and a set of statistically significant features were subsequently obtained by dimension reduction. The prediction model was established through binary classification logistic regression and employed to externally test the validation set by the method of confusion matrix. Meanwhile, ROC analysis was applied to assess the diagnostic performance of the model. Results: Of the 72 axillary lymph nodes, 35 were metastatic negative and 37 were positive. The consistency of enhanced MRI radiomics features was good, between 0.841 and 0.980. Uniformity, ClusterProminence_AllDirection_offset1_SD, Correlation_AllDirection_offset1, LongRunEmphasis_angle90_offset7 and SurfaceVolumeRatio were statistically significant differences (P<0.01), the area under the ROC between 0.747 and 0.931. In the training and testing group, the areas under the ROC, sensitivity, specificity and accuracy of the model were 0.953, 0.893, 0.926, 92.6% (50/54) and 0.944, 0.900, 1.000, 88.9% (16/18) respectively. Conclusion The prediction model based on radiomic features may provide a non-invasive and effective approach to the assessment of the risk of ALN metastasis of breast cancer.

We aimed to express and purify three rabies virus glycoproteins with different tags and sizes. After analyzing their binding function, we wish to obtain a rabies virus glycoprotein with higher affinity and ability to specifically bind memory B cells. Experiments were carried out to express full length, as well as the ectodomain RVG by gene engineering method. Combined with the antibody of CD19 and CD27, the candidate protein labeling with fluorescence was used to analyze its binding function. Flow cytometry was used to detect the anti-rabies virus specific memory B cells in PBMCs, and confirm the binding ability between the candidate proteins and anti-rabies virus-specific memory B cells. We successfully constructed three expression vectors pGEX-5X-1-RVG, pET28a-RVG and pET30a-G. Three glycoproteins GST-RVG, His-RVG and His-G were obtained by optimized expression and purification conditions. The antigen specificity of purified GST-RVG, His-RVG and His-G were identified by Western blotting and ELISA. The affinity of these three purified glycoproteins to anti-rabies virus antibody were detected by competitive ELISA. Anti-rabies virus specific memory B cells in positive PBMCs gained from people who had ever been injected with the vaccine can be detected by flow cytometry. Thus, we got a recombinant rabies virus glycoprotein that had high-affinity and could sort antigen specific memory B cells.

Objective To discover the operating problems through analysis of the financial situations of the rehabilitation institutions. Methods According to the different regions and different levels of rehabilitation institutions, 416 representative institutions from 26 provinc-es, municipalities and autonomous regions were surveyed. Results 329 effective questionnaires were recalled. 57.75%institutions relied on the superior departments in charge of funding, 51.09%institutions were in breakeven state. They were lack of sustainable development pow-er, and the capital expenditure was mainly used for staff salaries and equipment purchase. Conclusion To solve the shortage of funds in the development of rehabilitation institutions, we should establish a long-term mechanism of internal and external compensation.

Objective:To study the chemical constituents in the roots of Tripterygium wilfordii. Methods: The compounds from Tripterygium wilfordii were isolated and purified by silica gel, Sephadex LH-20 and prep-HPLC chromatography, and their structures were elucidated based on the physiochemical properties and spectroscopic analysis. Results:Twelve compounds were isolated and iden-tified as wilforgine(1),wilforine(2),triptonoterpene methyl ether(3),glut-5-en-3β,28-diol(4),wilforol E(5),triptobenzene L (6),maytenoic acid(7),triptophenolide(8),celastrol(9),demethylzeylasteral(10),1-desacetyl wilforgine(11) and wilfortrine (12). Conclusion:The 1D and 2D NMR data of 1 and 2 are assigned for the first time,and the absolute configurations of 1 are con-firmed by X-ray single crystal diffraction.