ObjectiveTo explore the "efficacy-toxicity" association mechanisms of Tripterygium wilfordii polyglycoside tablets （TWPT） by establishing and analyzing an interaction network associated with the clinical efficacy of TWPT in the treatment of rheumatoid arthritis （RA） and TWPT-induced liver injury. MethodOn the basis of the TWPT efficacy-related gene expression profile and TWPT-induced liver injury-related protein expression profile which were both obtained from our clinical cohorts， the "efficacy-toxicity" association network of TWPT was constructed， and the key network targets were identified by calculating the topological values of the nodes， including the degree， closeness and betweenness. After that， the biological functions and pathways of the key network targets were investigated by enrichment analysis. ResultA total of 119 differentially expressed genes （58 up-regulated and 61 down-regulated） between RA patients with TWPT well and weak response were identified as TWPT efficacy-related genes by clinical transcriptomics， and 49 differentially expressed proteins （36 up-regulated and 13 down-regulated） were demonstrated to be TWPT-induced liver injury-related proteins by clinical proteomics. In addition， the clinical symptom enrichment analysis indicated that the TWPT efficacy-related genes were significantly associated with various clinical symptoms of arthralgia in traditional Chinese medicine and clinical phenotypes of modern medicine， and most of the TWPT-induced liver injury-related proteins were involved in digestive system abnormalities. Therefore， the aforementioned multi-omics data represented the main clinical symptoms of TWPT treating RA and inducing liver injury. Mechanically， the "efficacy-toxicity" association network revealed that both TWPT efficacy-related genes and TWPT-induced liver injury-related core proteins were involved in the "immune-inflammatory" imbalance， especially playing an important role in neutrophil degranulation， complement cascade reaction， and immune-inflammatory response mediated by protein post-translational modification. Notably， the above genes and proteins were also enriched in various signaling pathways related to cell proliferation and cell cycle regulation， such as RAS and mitogen-activated protein kinase （MAPK） signaling pathway， and in several liver functional processes， such as glycogen metabolism and redox reaction. ConclusionThis study systematically explained the "efficacy-toxicity" association characteristics and molecular mechanisms of TWPT by applying a research strategy integrating clinical phenomics， transcriptomics and proteomics， laying a good data foundation for exploring the "efficacy enhancing and toxicity-reducing" mechanisms of TWPT.

Objective To predict the potential suitable habitat of Haemaphysalis concinna in Heilongjiang Province under different climatic scenarios. Methods The geographic locations of ticks in Heilongjiang Province from 1980 to 2022 were captured from literature review and field ticks monitoring data from Harbin Center for Disease Control and Prevention in Heilongjiang Province, and the tick distribution sites with spatial correlations were removed using the software ArcGIS 10.2. The environment data under historical climatic scenarios from 1970 to 2000 and the climatic shared socioeconomic pathways (SSP) 126 scenario model from 2021 to 2040 and from 2041 to 2060 were downloaded from the WorldClim website, and the elevation (1 km, 2010), population (1 km grid population dataset of China, 2010) and annual vegetation index (1 km, 2010) data were downloaded from the Resource and Environmental Science and Data Center, Institute of Geographical Sciences and Natural Resources, Chinese Academy of Sciences. The contribution of environmental factors to H. concinna distribution was evaluated and environmental variables were screened using the software MaxEnt 3.4.1 and R package 4.1.0, and the areas of suitable habitats of H. concinna and changes in center of gravity were analyzed using the maximum entropy model in Heilongjiang Province under different climatic scenarios. In addition, the accuracy of the maximum entropy model for prediction of H. concinna distribution was assessed using the area under curve (AUC) of the receiver operating characteristic curve. Results A total of 79 H. concinna distribution sites and 24 environmental variables were collected, and 70 H. concinna distribution sites and 9 environmental factors that contributed to distribution of the potential suitable habitats of H. concinna in Heilongjiang Province were screened. The three most significant contributing factors included precipitation seasonality, annual precipitation, and mean temperature of the driest quarter, with cumulative contributions of 60.7%. The total area of suitable habitats of H. concinna was 29.05 × 10⁴ km² in Heilongjiang Province under historical climatic scenarios, with the center of gravity of suitable habitats located at (47.31° N, 129.16° E), while the total area of suitable habitats of H. concinna reduced by 0.97 × 10⁴ km² in Heilongjiang Province under the climatic SSP126 scenario from 2041 to 2060, with the center of gravity shifting to (47.70° N, 129.28° E). Conclusions The distribution of suitable habitats of H. concinna strongly correlates with temperature and humidity in Heilongjiang Province. The total area of potential suitable habitats of H. concinna may appear a tendency towards a decline with climatic changes in Heilongjiang Province, and high-, medium- and low-suitable habitats may shift.

Objective:To investigate the segmentation methods of pancreatic ductal adenocarcinoma (PDAC) tumor regions in 18F-fluorodeoxyglucose (FDG) PET/CT images, as well as their impact on radiomic features-based pathological grade prediction. Methods:A total of 72 patients (46 males, 26 females, age range: 25-87 years) with pathologically confirmed PDAC and a preoperative 18F-FDG PET/CT scan in Peking Union Medical College Hospital between September 2010 and January 2016 were enrolled retrospectively. The cohort of patients was classified as well differentiated group and non-well differentiated group based on the pathological grade of PDAC, and patients were divided into training set and validation set in the ratio of 3∶1 randomly. Two physicians performed manual contours in the tumor region (referred as region of interest (ROI)_M1 and ROI_M2) and semi-automatic ROIs based on standardized uptake value (SUV) gradient edge search (referred as ROI_G) and 40% threshold applied to the maximum SUV (SUV max; referred as ROI_S) were drawn. The four types of segmentation results were compared in terms of volume and Dice similarity coefficient (DSC). Shape, first-order, and texture features were extracted from PET/CT original and preprocessed images, and the interclass correlation coefficient (ICC) was used to assess each feature′s consistency across all segmentations. Kruskal-Wallis rank sum test, independent-sample t test or z test were used to analyze the data. The area under the receiver operating characteristic curve was used to assess model accuracy, and cross validation was used to assess generalization ability. Results:There were 55 patients in the training set (14 well differentiated cases and 41 non-well differentiated cases) and 17 patients in the validation set (4 well differentiated cases and 13 non-well differentiated cases). A total of 44 selected features were predictive of the pathological grade of PDAC among 20 feature groups. There was significant difference among the volumes of ROI_M1, ROI_M2, ROI_G and ROI_S (10.29(4.01, 19.43), 9.34(4.26, 17.27), 11.86(5.52, 19.74) and 15.08(9.62, 27.44) cm 3; H=18.641, P<0.05). The degree of contour coincidence and feature consistency between ROI_M1 and ROI_M2 were both higher (DSC=0.86 (0.76, 0.90), ICC=0.86 (0.74, 0.94)). Compared to manual contours, the degree of contour coincidence and feature consistency of ROI_G (DSC: 0.86(0.75, 0.91), 0.91(0.85, 0.96); ICC: 0.87(0.72, 0.94), 0.94(0.88, 0.98)) were better. There was no statistically significant difference in model accuracy or generalization ability between ROI_M1 and ROI_G ( z=1.052, t=0.712, both P>0.05). The accuracy of ROI_M2 was better than ROI_G ( z=3.031, P=0.002), but the generalization ability of ROI_M2 was insufficient ( t=3.086, P=0.012). Conclusions:Although the manual contour prediction models are highly accurate, their performance are unstable. Semi-automatic contouring based on gradient can achieve comparable accuracy to manual contouring, and the model′s generalization ability is stronger.

OBJECTIVE： To obtain Ginkgo biloba antimicrobial peptide （GBA） recombinant protein， and to investigate in vivo/in vitro antimicrobial activity of the protein so as to provide experimental basis for solving bacterial resistance and large-scale production of new plant-derived antimicrobial agents. METHODS： Based on gene technology， according to GBA gene sequence   （FJ 865399） published by Genebank， recombinant expression vector plasmid pET32a（+）-GBA was constructed. Prokaryotic expression of recombinant protein was conducted by Escherichia coli， and then the protein was purified and identified by gel electrophoresis and Western blotting. Drug sensitivity of obtained recombinant protein to E. coli， Staphylococcus aureus， Pseudomonas aeruginosa， Salmonella typhimurium were investigated by Kirby-Bauer test. The minimum antibacterial concentration （MIC） and minimum bactericidal concentration （MBC） were determined by broth dilution method. The protective effects of recombinant protein on S. aureus infection model mice were investigated. RESULTS： Target recombinant protein was expressed successfully and purified （molecular weight of 32 kDa）. The recombinant protein was moderately sensitive to S. aureus and low sensitive to other three bacterias. MIC and MBC of the recombinant protein to S. aureus were （50.00±5.00）mg/mL and（138.33±12.58）mg/mL， and MIC was significantly higher than those to other 3 kinds of bacterias （P＜0.05）. High-dose of recombinant protein （8.0 g/kg） could significantly reduce the S. aureus-induced mortality of mice （P＜0.05）， and had similar protective effect as positive drug penicillin. CONCLUSIONS： Obtained recombinant protein has obvious antimicrobial effects on S. aureus， inhibits E. coli and P. aeruginosa to certain extent and shows poor inhibitive effect on S. typhimurium. High-dose of  recombinant protein shows significant protective effect for S. aureus infection model mice.

Objective To explore the application value of the real-time three-dimensional ultrasound Bi plane technology in evaluation of the foramen ovale blood in fetus.Methods The coronal plane of inferior vena cava entering the right atrium in 186 normal fetuses were obtained.The dimensions of foramen ovale (DFO) and inferior vena cava at the entrance of right atrium (DIVC) were measured in the coronal plane.The ratio of DFO and DIVC (DFO/DIVC) was calculated.The correlation be tween DFO/DIVC and gestational age was analyzed.Results There was no correlation between DFo/DIvc and gestational age (r=0.228,P＞0.05).There were 155 cases during second trimester (21 28 weeks),and the DFO was (4.46±0.57)mm,DIVC was (4.55±1.22)mm,DFO/DIVC was 1.03±0.22.There were 31 cases during late pregnancy (29-36 weeks),and the DFO was (5.20±0.43)mm,DIVC was (5.90±1.33)mm,DFO/DIVC was 0.92±0.17.The mean 95％ confidence interval of DFO/DIVC was (0.98,1.04),the 95％ normal reference range was (0.80,1.44).Conclusion The coronal plane of inferior vena cava entering the right atrium can be obtained with real-time three-dimensional ultrasound Bi-plane technology,the flow from the inferior vena cava enters right atrium which is divided by the upper atrial septum can be observed,which is important in evaluating the foramen ovale blood.

The foramen ovale (FO) is an important intra-atrium communication in fetuses.FO restriction or closure in fetuses with or without congenital heart defects can cause hemodynamics abnormality in utero.Fetal echocardiography plays an irreplaceable role in diagnosis of disease about FO.Progresses of ultrasound in fetuses with restricted or premature closed FO were reviewed in this article.

Objective To analyze the abnormal fetal ductus arteriosus (DA) by echocardiography.Methods Seventy fetuses of abnormal DA diagnosed prenatally were retrospectively reviewed.Transverse scans combined with color Doppler were used to acquire four chamber view,left and right ventricular outflow tract views,three vessel view,and three-vesseltrachea view.In addition,sagittal scans with color Doppler were used to get vena cava long axis view,aortic arch view,and ductal arch view.The spatial relationship of the great arteries and trend of DA were observed.Results Abnormal fetal DA is mainly composed of DA absence,DA abnormal function and DA morphological abnormality.Among 70 cases of fetal DA,9 cases were diagnosed with DA absence,8 cases were DA atresia,11 cases were DA completed closure nearly,9 cases were shown with reverse DA blood perfusion,33 cases were shown with DA curvature and dilatation.Conclusion Prenatal diagnosis of DA absence and DA abnormal function is of great significance.Three-vessel-trachea view and ductal arch view combined with CDFI can make a definitive diagnosis.

Objective To explore the ultrasonographic method in fetal coronary sinus (CS) dilation.Methods Totally 145 normal fetuses (normal group) and 72 fetuses of CS dilation (CS group) diagnosed prenatally were retrospectively reviewed.The long axis of coronary sinus was displayed in the non-standard four chamber view and the area of the sagittal view of CS was measured.Transverses scans combined with color Doppler were used to acquire four chamber view,left and right ventricular outflow tract views,three vessel view.In addition,sagittal scans with color Doppler were used to get short-axis view at the level of great arteries,vena cava long axis view,aortic arch view,and ductal arch view.The characteristics of CS were observed.Results CS area of sagittal view was positively correlated with gestational age (normal group:r=0.954,P＜0.05;CSgroup:r=0.904,P＜0.05).In the samegestational weeks,the CS area of the sagittal view in the normal group was less than that in the CS group (all P＜0.01).In CS group,52 fetuses were persistent left superior vena cava,15 fetuses were total anomalous pulmonary venous connection,5 fetuses were associated with right heart pressure overload.Conclusion Fetal CS sagittal section area is positively correlated with gestational age.When the fetal heart ultrasonography found CS dilation,other intracardiac malformations should also be considered.The etilogies of CS dilation should be analyzed clinically through multi-slice,multi-angle scanning.

Objective To explore the correlation between the expressions of matrix metalloproteinase -9 (MMP-9), Toll-likeReceptor 4 ( TLR4) and lung revascularization in patients with chronic obstructive pulmonary disease .Methods Lung tissues frompatients with chronic obstructive pulmonary disease (COPD) (COPD group,n =25) and those without COPD (non-COPD group,n =25) were obtained from surgically resected specimens .The ratio of the area of the wall to that of the pulmonary arterioles (WA %) andthe ratio of the thickness of the wall to the external diameter of the pulmonary arterioles (WT %) were analyzed by computer-based imageanalysis system.Immunohistochemical technique was applied to investigate the expressions of TLR 4, proliferative cell nuclear antigen(PCNA) and MMP-9 in vascular smooth muscle cells.Results ⑴ The inflammatory infiltration degree, WA %, and WT %were significantly higher than that of non -COPD group ( P <0.01), respectively.⑵Compared with non-COPD group, the expressionsof PCNA, TLR4, and MMP-9 in vascular smooth muscle cells were increased significantly ( P <0.01).⑶The expressions of TLR4,MMP-9 had a positive correlation with WA%, WT%, degree of inflammatory infiltration, and the expression of PCNA ( r =0.67,0.74,0.47,0.44;0.59,0.71,0.61,0.33, P <0.01), up-regulated expression of TLR4 was closely related with the expression of MMP-9 ( r =0.55, P <0.01).Conclusions The pulmonary arterioles of COPD patients showed marked inflammatory and arteriolemuscularization, the TLR4 might aggravate inflammation,induced upregulation of MMP-9 expression, played an important role in the pulmonary vascular remodeling process.

Objective To investigate the expression of aquaporin (AQP) 1, AQP4, inward rectifying potassium channel 4.1 (Kir4.1) and cytoskeleton features of rat spinal cord astrocytes after cytochalasin D (CytD) intervention. Methods Spinal cord astrocytes isolated from 2~3-day-old rats were cultured till confluency. MTT was used to assess survival rate of astrocytes 2 h, 12 h and 24 h after co-cultured with 0.05 μg/ml, 0.10 μg/ml, 0.20 μg/ml, 0.40 μg/ml, 0.80 μg/ml and 1.00 μg/ml of CytD, respectively. Confocal microscopy was used to observe cytoskeleton features of astrocytes 2 h after co-cultured with 0.05 μg/ml, 0.10 μg/ml, 0.20 μg/ml, 0.40 μg/ml of CytD. The expression of AQP1, AQP4, Kir4.1 mRNA were determined with real-time PCR 2 h after co-cultured with 0.05 μg/ml, 0.10 μg/ml, 0.20 μg/ml, 0.40 μg/ml, 0.80 μg/ml and 1.00 μg/ml of CytD. Results The survival rate of rat spinal cord astrocytes reduced with the time of co-culture and concentration of CytD (P<0.05). The cytoskeleton of astrocytes was reconstructed. The expression of AQP1, AQP4 and Kir4.1 mRNA increased after co- cultured with 0.05~0.40 μg/ml of CytD. Conclusion The appropriate dosage of CytD may remodel the cytoskeleton and increase the mRNA expression of AQP1, AQP4 and Kir4.1 in spinal cord astrocytes of rats.