This study aims to explore the effects and action mechanisms of the active ingredients in Buyang Huanwu Decoction(BYHWD), namely tetramethylpyrazine(TMP) and hydroxy-safflor yellow A(HSYA), on oxygen-glucose deprivation/reglucose-reoxygenation(OGD/R)-induced inflammation and oxidative stress of microglia(MG). Network pharmacology was used to screen the effective monomer ingredients of BYHWD and determine the safe concentration range for each component. Inflammation and oxidative stress models were established to further screen the best ingredient combination and optimal concentration ratio with the most effective anti-inflammatory and antioxidant effects. OGD/R BV2 cell models were constructed, and BV2 cells in the logarithmic growth phase were divided into a normal group, a model group, an HSYA group, a TMP group, and an HSYA + TMP group. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of inflammatory cytokines such as interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6). Oxidative stress markers, including superoxide dismutase(SOD), nitric oxide(NO), and malondialdehyde(MDA), were also measured. Western blot was used to analyze the protein expression of both inflammation-related pathway [Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)] and oxidative stress-related pathway [nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)]. Immunofluorescence was used to assess the expression of proteins such as inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1). The most effective ingredients for anti-inflammatory and antioxidant effects in BYHWD were TMP and HSYA. Compared to the normal group, the model group showed significantly increased levels of IL-1β, TNF-α, IL-6, NO, and MDA, along with significantly higher protein expression of NF-κB, TLR4, Nrf2, and HO-1 and significantly lower SOD levels. The differences between the two groups were statistically significant. Compared to the model group, both the HSYA group and the TMP group showed significantly reduced levels of IL-1β, TNF-α, IL-6, NO, and MDA, lower expression of NF-κB and TLR4 proteins, higher levels of SOD, and significantly increased protein expression of Nrf2 and HO-1. Additionally, the expression of the M1-type MG marker iNOS was significantly reduced, while the expression of the M2-type MG marker Arg-1 was significantly increased. The results of the HSYA group and the TMP group had statistically significant differences from those of the model group. Compared to the HSYA group and the TMP group, the HSYA + TMP group showed further significant reductions in IL-1β, TNF-α, IL-6, NO, and MDA levels, along with significant reductions in NF-κB and TLR4 protein expression, an increase in SOD levels, and elevated Nrf2 and HO-1 protein expression. Additionally, the expression of the M1-type MG marker iNOS was reduced, while the M2-type MG marker Arg-1 expression increased significantly in the HSYA + TMP group compared to the TMP or HSYA group. The differences in the results were statistically significant between the HSYA + TMP group and the TMP or HSYA group. The findings indicated that the combined use of HSYA and TMP, the active ingredients of BYHWD, can effectively inhibit OGD/R-induced inflammation and oxidative stress of MG, showing superior effects compared to the individual use of either component.
Oxidative Stress/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Mice ; Glucose/metabolism* ; Cell Line ; Inflammation/genetics* ; Oxygen/metabolism* ; Pyrazines/pharmacology* ; Microglia/metabolism* ; NF-E2-Related Factor 2/immunology* ; NF-kappa B/immunology* ; Toll-Like Receptor 4/immunology* ; Anti-Inflammatory Agents/pharmacology* ; Humans

BACKGROUND: The detection of pulmonary nodules is a key step to achieving the early diagnosis and therapy of lung cancer. Deep learning based Artificial intelligence (AI) presents as the state of the art in the area of nodule detection, however, a validation with clinical data is necessary for further application. Therefore, the aim of this study is to evaluate the performance of AI in the detection of malignant and non-calcified nodules in chest CT. METHODS: Two hundred chest computed tomography (CT) data were randomly selected from a self-built nodule database from Tianjin Medical University General Hospital. Both the pathology confirmed lung cancers and the nodules in the process of follow-up were included. All CTs were processed by AI and the results were compared with that of radiologists retrieved from the original medical reports. The ground truths were further determined by two experienced radiologists. The size and characteristics of the nodules were evaluated as well. The sensitivity and false positive rate were used to evaluate the effectiveness of AI and radiologists in detecting nodules. The McNemar test was used to determine whether there was a significant difference. RESULTS: A total of 889 non-calcified nodules were determined by experts on chest CT, including 133 lung cancers. Of them, 442 nodules were less than 5 mm. The cancer detection rates of AI and radiologists are 100%. The sensitivity of AI on nodule detection was significantly higher than that of radiologists (99.1% vs 43%, P<0.001). The false-positive rate of AI was 4.9 per CT and decreased to 1.5 when nodules less than 5 mm were excluded. CONCLUSIONS AI achieves the detection of all malignancies and improve the sensitivity of pulmonary nodules detection beyond radiologists, with a low false positive rate after excluding small nodules.
Artificial Intelligence ; Deep Learning ; Humans ; Lung Neoplasms ; diagnosis ; diagnostic imaging ; Multiple Pulmonary Nodules ; diagnosis ; diagnostic imaging ; Tomography, X-Ray Computed

OBJECTIVE： To establish antibiotics use rationality evaluation model in type Ⅰ incision surgery patients， and to provide reference for prescription review of clinical pharmacists. METHODS： Totally 432 inpatients underwent type Ⅰ surgical incision in a hospital from Jan. 1st- Dec. 31st， 2017 were selected as the research objects. The information of diagnosis and treatment including age， nosocomial infection， the number of kinds of antibiotics used were extracted. Based on the results of clinical pharmacists’ comments on the antibiotics use rationality in patients’ prevention and treatment， non-conditional Logistic regression and support vector machine （SVM） in machine learning method were used to convert clinical pharmacists’ comments into objective index that can be recognized by the machine learning model， using categories of antibiotics （preventive or therapeutic use） as dependent variables and the patient’s diagnosis and treatment information as independent variables. Classification and identification model was established for antibiotics use rationality in type Ⅰ incision surgery patients. Using sensitivity， specificity and Youden index as indexes， established mode was validated on the other 61 samples of type Ⅰ incision surgery patients. The rationality of antibiotics prescriptions in type Ⅰ incision surgery patients before （by manual review， Jan.-Dec. 2017） and after （Jan.-Oct. 2018） using the model were collected， and the effects of the model were evaluated. RESULTS： The sensitivity， specificity and Youden index of non-conditional Logistic regression model were 65.63％， 75.00％ and 40.63％， respectively. Main parameters of the model established by SVM included gamma 0.01， cost 10， sensitivity 92.19％， specificity 87.50％， Youden index 79.69％. The model established by SVM was better than non-conditional Logistic regression. SVM was used to validate established mode， and sensitivity， specificity and Youden index were 100％， 88.57％ and 88.57％， respectively. Compared with before using the model， the evaluation ratio increased from 69.44％ to 100％， the rate of prophylactic use of antibiotics decreased from 23.84％ to 16.43％， the rate of rational drug type selection increased from 37.86％ to 54.39％， and treatment course shortened from 5.01 days to 3.26 days after using the model. CONCLUSIONS： Established antibiotics use rationality evaluation model in typeⅠincision surgery patients by SVM in machine learning method fully covers all the patients， promotes rational use of antibiotics in typeⅠincision surgery patients， and provides a new idea for pharmacist prescription comment.

Background and objective The computed tomography (CT) follow-up of indeterminate pulmonary nodules aiming to evaluate the change of the volume and CT value is the common strategy in clinic. The CT dose needs to considered on serious CT scans in addition to the measurement accuracy. The purpose of this study is to quantify the preci-sion of pulmonary nodule volumetric measurement and CT value measurement with various tube currents and reconstruction algorithms in a phantom study with dual-energy CT.Methods A chest phantom containing 9 artificial spherical solid nodules with known diameter (D=2.5 mm, 5 mm, 10 mm) and density (-100 HU, 60 HU and 100 HU) was scanned using a 64-row detector CT canner at 120 Kilovolt & various currents (10 mA, 20 mA, 50 mA, 80 mA,100 mA, 150 mA and 350 mA). Raw data were reconstructed with filtered back projection and three levels of adaptive statistical iterative reconstruction algorithm (FBP, ASIR; 30%, 50% and 80%). Automatic volumetric measurements were performed using commercially available software. The relative volume error (RVE) and the absolute attenuation error (AAE) between the software measures and the reference-standard were calculated. Analyses of the variance were performed to evaluate the effect of reconstruction methods, different scan parameters, nodule size and attenuation on the RPE.Results The software substantially overestimated the very small (D=2.5 mm) nodule's volume [mean RVE: (100.8%±28%)] and underestimated it attenuation [mean AAE: (-756±80) HU]. The mean RVEs of nodule with diameter as 5 mm and 10 mm were small [(-0.9%±1.1%)vs (0.9%±1.4%)], however, the mean AAEs [(-243±26) HUvs (-129±7) HU)] were large. The ANOVA analysis for repeated measurements showed that different tube current and reconstruction algorithm had no significant effect on the volumetric measurements for nodules with diameter of 5 mm and 10 mm (F=5.60,P=0.10 vs F=11.13,P=0.08), but significant effects on the measurement of CT value (F=34.79, P<0.001 vs F=156.14, P<0.001).Conclusion An infinitesimally small errors of volumetric measurement of 5 mm or 10 mm nodule could achieved with very low current and ASIR reconstruction, suggesting a possibility of remarkable radiation dose reductions, while it is not applicable for 5 mm nodule. The attenuation acquired through three dimensional software has large measurement error and can not applied in clinical currently.

Computed tomography (CT) follow-up of indeterminate pulmonary nodules and the quantification of growth characteristics are the commonly adopted strategy in clinical setting. The volume/mass doubling time can be used to quantify the growth velocity based on exponential growth model. Therefore, we reviewed the followed aspects on growth evaluation of pulmonary nodules on chest CT, including the growth model of lung cancer, the methods used for nodule growth quantification and the growth characteristics of different types of pulmonary nodules.

Background and objective hTe management of pulmonary nodules relies on cancer risk assessment, in which the only widely accepted criterion is diameter. hTe development of volumetric computed tomography (CT) and three-dimensional (3D) sotfware enhances the clarity in displaying the nodules’ characteristics. hTis study evaluated the values of the nodules’ volume and 3D morphological characteristics (edge, shape and location) in cancer risk assessment.Methods hTe CT data of 200 pulmonary nodules were retrospectively evaluated using 3D volumetric sotfware. hTe malignancy or benignity of all the nodules was conifrmed by pathology, histology or follow up (>2 years).Logistic regression analysis was performed to calculate the odds ratios (ORs) of the 3D margin (smooth, lobulated or spiculated/irregular), shape (spherical or non-spherical), location (purely intraparenchymal, juxtavascular or pleural-attached), and nodule volume in cancer risk assessment for total and sub-centimeter nodules. hTe receiver operating characteristic (ROC) curve was employed to determine the opti-mal threshold for the nodule volume.Results Out of 200 pulmonary nodules, 78 were malignant, whereas 122 were benign. hTeLogistic regression analysis showed that the volume (OR=3.3;P<0.001) and the 3D margin (OR=13.4, 9.8; bothP=0.001) were independent predictive factors of malignancy, whereas the location and 3D shape exhibited no total predictive value (P>0.05). ROC analysis showed that the optimal threshold for malignancy was 666 mm3. For sub-centimeter nodules, the 3D margin was the only valuable predictive factor of malignancy (OR=60.5, 75.0;P=0.003, 0.007).Conclusion hTe volume and 3D margin are important factors considered to assess the cancer risk of pulmonary nodules. Volumes larger than 666 mm3 can be determined as high risk for pulmonary nodules; by contrast, nodules with lobulated, spiculated, or irregular margin present a high malignancy probability.

Objective:To express fusion protein of mouse thymic stromal lymphopoietin (TSLP) and HIV-1 gp120BAL V1/V2 subdomain in 293F cell.Methods:Full length of the V1V2 sequence from BAL isolate was fused with the C-terminus of mouse thymic stromal lymphopoietin (TSLP) and sub-cloned into pCEP-Pu vector to construct the eukaryotic expression plasmid-pCTV1V2BAL.The recombinant plasmid was confirmed by enzyme digestion and sequencing , then transfected into 293 F cells using PEI as a transfection reagent .The fusion protein was purified by metal chelate affinity chromatography and characterized by SDS -PAGE and Western blot . The epitopes of V1/V2 in fusion protein were identified by ELISA .Results:The SDS-PAGE and Western blot results showed that there were highly heterogeneous glycoprotein bands at the site between 35 kD and 55 kD, which reacted with anti-mTSLP rabbit polyclonal antibody and anti-His tag mouse monoclonal antibody .The ELISA analysis showed that antibodies to V 1/V2BAL existed in the sera of HIV-1 positive patients.Conclusion:The mTSLP-V1/V2 fusion protein was successfully expressed in 293F cells, which may be useful for HIV-1 vaccine research .

Background and objective Sotfware oriented three-dimensional (3D) volumetric measurement of pul-monary nodules has been feasible in the follow-up of indeterminate pulmonary nodules, however, its value need a further vali-dation. hTe purpose of this study is to retrospectively analyze the chest CT data of patients with pulmonary nodules to compare the intra-observer variability of 3D and two-dimensional (2D) volumetric measurement. Methods Eighty-six pulmonary nod-ules in chest CT scans of 79 subjects were retrospectively analyzed. One radiologist measured the nodules twice with a 7 days interval using 2D and 3D methods respectively. hTe maximal diameter (X), the perpendicular diameter (Y) on maximal cross sectional area of the nodule and the caudo-cranial diameter (Z) were measured and the volume was calculated by two models:spherical and elliptical model. hTe 3D measurements were acquired with semi-automated sotfware with manual adjustment on unsatisifed nodule segmentation. Logistic regression analysis was performed to evaluate the effect of nodule location and mor-phology on 3D nodule segmentation. ANOVA and correlation test were used to evaluate the difference among three methods. Bland-Altman method was applied to quantify the intra-observer variability. Results Sotfware achieved satisifed segmentation for 86.4%nodules. hTe irregular and juxtavacular nodules have signiifcantly high odds rations (OR) of unsatisifed segmenta-tion as 4.0, 4.5, respectively. hTe volume measured by three method was signiifcantly different (F=6.5, P=0.012), while the repeated measurements did not led to signiifcant difference (F=1.813, P=0.182). hTe Spearman correlation effcient between 3D volume and 2D volume with sphere and ellipsoid model was 0.97, 0.88. hTe 95%limits of agreement of RD between two repeated measurements were-14%-11.6%,-37.7%-39.9%and-39.8%-45.8%for 3D, 2D with elliptical model and spherical model, respectively. Conclusion hTe 3D volume measurement of pulmonary nodules is more repeatable than 2D volume measurement. Unsatisifed segmentation can occurred on a small number of nodules, especially for irregular and juxtavascular nodules. For these nodules, the measurement of 3D diameters is recommended.

Objective To investigate the feasibility of reduced radiation dose for CT pulmonary angiography (CTPA) and the possible lowest radiation threshold by a phantom study.Methods The CT value difference between air within the trachea and the extracorporeal background region was measured in132 consecutive patients.A noise-measurement phantom and a pulmonary embolism (PE) phantom were made of phenol-formaldehyde, and both phantoms and a water phantom were scanned with standard and lower radiation doses as follow: 280, 200, 160, 100, 90, 80, 70, 60, 50, 40, 30, 20, 15, and 10 mA respectively, at a fixed voltage of 120 kVp.Standard and soft tissue algorithms were used to reconstruct the images.Three experienced doctors independendy evaluate the image quality and the efficiency of detecting PE of the images with various doses.The Pearson correlation analysis, two-tailed paired t test, ANOVA, and Kappa test were employed for the statistical analysis.Results The CT value difference between air within the trachea and the extracorpereal background region in 132 consecutive patients ranged from 20.00 to 55.00 HU, which had a positive correlation with weight[(64.99±11.86) kg], weight-height ratio [(38.71±6.13) kg/m], and BMI[(23.11±3.38) kg/m2](r=0.228,0.374,0.449 respectively; P <0.01).The image noise level with soft-tissue reconstruction algorithm[(16.55±9.08), (16.42±9.40) HU]was significantly lower than that of the image with standard reconstruction algorithm[(22.43±11.25),(21.99±11.67) HU](F=4.316, P < 0.05).The image noise level with soft-tissue reconstruction algorithm at 100 mA was similar to that of the images with standard reconstruction algorithm at 280 mA, and the signal-w-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the image of PE phantom was 23.05 and 20.52 respectively, without any impairment in detectability of embolus.The image noise level with soft-tissue reconstruction algorithm at 60 mA was similar to that of the image with standard reconstruction algorithm at 160 mA, while the SNR and CNR was 18.01 and 15.97 respectively, also with acceptable detectability of embolus.When the tube current was reduced below 30 mA, the image quality decreased significantly, with the SNR and CNR was lower than 12.36 and 10.95 respectively, and the detectability of embolus was degraded.The consistency of the image quality grading by 3 observers was excellent(K=0.807,0.712,0.904 ,respectively; P < 0.01).Conclusions The 100 mA may potentially be the ideal low dose tube current setting, with radiation dose only equal to 36% of 280 mA (standard dose).The 30 mA may possibly be a minimum radiation dose for detecting PE.The soft-tiasue reconstruction algorithm was favorable in preserving the SNR when the radiation dose was reduced.