OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of apixaban in the prevention and treatment of cancer-associated venous thromboembolism （CA-VTE）， and provide evidence-based reference for clinical treatment. METHODS Retrieved from PubMed， the Cochrane Library， CNKI， Wanfang， VIP database and other websites of health technology assessment （HTA）， systematic review/meta-analysis， pharmacoeconomic studies and HTA reports of apixaban in the prevention and treatment of CA-VTE were collected. After data extraction and quality evaluation， the results of the included study were analyzed descriptively. RESULTS A total of 23 literatures were included， involving 16 systematic review/meta-analysis and 7 pharmacoeconomic studies. In terms of efficacy， compared with placebo， prophylactic use of apixaban could significantly reduce the incidence of venous thromboembolism （VTE） in outpatient adult cancer patients receiving chemotherapy （P＜0.05）. Compared with low-molecular weight heparin （LMWH）， rivaroxaban and warfarin， there were no statistically significant differences in the incidence of VTE for apixaban （P＞0.05）； nevertheless， apixaban was ranked as the most preferable choice. For the treatment of patients with CA-VTE， compared with warfarin， apixaban could significantly reduce the recurrence rate of VTE （P＜0.05）. While compared with patients treated with LMWH， rivaroxaban， edoxaban and dabigatran， there were no statistically significant differences in the recurrence rates of VTE， deep venous thrombosis and pulmonary embolism among patients using apixaban （P＞0.05）. In terms of safety， compared with placebo， prophylactic use of apixaban showed a higher occurrence of major bleeding in outpatient adult cancer patients receiving chemotherapy （P＜0.05）， while compared withpatients treated with LMWH， rivaroxaban， and warfarin， there were no statistically significant differences in the incidence of major bleeding among patients using apixaban （P＞0.05）； despite this， apixaban was ranked as the most favorable option. For the treatment of patients with CA-VTE， compared with dalteparin， the incidence of major bleeding and all-cause mortality of apixaban were similar （P＞0.05）， while the incidence of clinically relevant non-major bleeding （CRNMB） was higher （P＜0.05）. Compared with edoxaban， the incidence of major bleeding of apixaban was reduced significantly （P＜0.05）， while there was no significant difference in the incidence of CRNMB， the incidence of clinically relevant bleeding and all-cause mortality （P＞0.05）. Compared with rivaroxaban， warfarin and dabigatran， there were no significant differences in the incidence of major bleeding， the incidence of CRNMB， the incidence of clinically relevant bleeding and all-cause mortality （P＞0.05）. In terms of cost-effectiveness， the researches in China showed that apixaban was cost-effective in preventing CA-VTE； foreign studies showed that apixaban was cost-effective in preventing and treating CA-VTE. CONCLUSIONS Apixaban is effective， safe and cost- effective in the prevention and treatment of CA-VTE.

Objective To develop a rapid and accurate Monte Carlo program(simplified code for dosimetry of carbon ions,SPEEDO)for carbon ion therapy.Methods For electromagnetic process,type Ⅱ condensed history simulation scheme and continuous slowing down approximation were used to simulate energy straggling,range straggling,multiple scattering,and ionization processes.For nuclear interaction,5 types of target nuclei were considered,including hydrogen,carbon,nitrogen,oxygen,and calcium.The produced secondary charged particles followed the same condensed history framework.The study simulated the transport of carbon ions in 4 materials(water,soft tissues,lung,and bone),and the calculated doses were validated against TOPAS(a Monte Carlo simulation software for radiotherapy physics),followed by a comparison with dose measurements in a water phantom from the HIMM-WW(a medical heavy-ion accelerator facility in Wuwei).Results SPEEDO's simulation results showed good consistency with TOPAS.For each material,in the voxel region where the physical dose was greater than 10％of the maximum dose point,the relative maximum dose error of both was less than 2％.At treatment energy of 400 MeV/u,SPEEDO's computation time was significantly less than that of TOPAS(13.8 min vs 105.0 min).SPEEDO's calculation results also showed good agreement with HIMM-WW measurements in terms of lateral dose distribution and integrated dose depth curve.Conclusion SPEEDO program can accurately and rapidly perform Monte Carlo dose calculations for carbon-ion therapy.

Objective To develop a GPU-based Monte Carlo dose calculation module for helical tomotherapy(TOMO),and integrate it into the commercial software ArcherQA to achieve fast and accurate dose verification in clinic.Methods The TOMO treatment head was modeled using TOPAS to obtain phase space files,and a fast weight tuning algorithm was used to simulate particle transport in multi-leaf collimator for improving computational efficiency,and finally,GPU-based Monte Carlo algorithms in ArcherQA were used to simulate particle transport in patients.To verify the model accuracy,the ArcherQA calculated results in water tank were compared with measured data for different open fields.In addition,multiple comparisons among ArcherQA results,TPS results and ArcCHECK results were conducted on 15 clinical cases(5 cases in the head and neck,5 cases in the chest and abdomen,and 5 cases in the whole body).Results In the water tank tests for 40 cm×5.0 cm,40 cm×2.5 cm and 40 cm× 1.0 cm radiation fields,the average global relative errors of the percentage depth dose,transverse dose distribution,and longitudinal dose distribution calculated by ArcherQA with the corresponding measured values were 0.72％,0.66％,and 0.54％,respectively.Over 98％of the voxels had a global relative error of less than 1％.As for 15 clinical cases,in 2％/2 mm criteria,the mean Gamma passing rate was 98.1％between ArcherQA and TPS,99.1％between TPS and ArcCHECK,and 99.4％between ArcherQA and ArcCHECK.The uncertainty of the simulation maintained less than 1％,and the average time taken for calculation based on patient CT vs ArcCHECK phantom was 87 s vs 64 s.Conclusion ArcherQA can be used for independent dose validation for TOMO plans for it can provide fast and accurate dose calculations.

ObjectiveTo discuss the effect of modified Gegen Qinliantang （MGQT） on blood glucose and lipids and Takeda G protein-coupled receptor 5 （TGR5）-related pathways in pancreatic tissue of obese type 2 diabetes mellitus （T2DM） mice. MethodA total of 10 male specific pathogen free （SPF） m/m mice （7 weeks old） and 50 male SPF （7 weeks old） were adaptively fed for one week in SPF laboratory. The m/m mice were included in the blank group. T2DM was induce d in the 50 db/db mice. The model mice were randomized into the model group， metformin group （0.2 g·kg^-1）， high-dose， medium-dose， and low-dose （31.9， 19.1， 6.4 g·kg^-1） MGQT groups， with 10 in each group， and the drug dose was10 mL·kg^-1. The model group and the blank group received distilled water of the same volume. The administration lasted 12 weeks （once/day）. Fasting blood glucose （FBG） was detected regularly. After 12 weeks of administration， serum levels of glycated serum protein （GSP）， serum glucose （GLU）， total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were detected. Pathological changes in the pancreatic tissue were based on hematoxylin-eosin （HE） staining. Western blot was used to determine the protein expression of TGR5， protein kinase A （PKA）， phosphorylated （p）-PKA， cyclic-AMP response element binding protein （CREB）， p-CREB， proprotein convertase 1/3 （PC1/3）， and glucagon-like peptide-1 （GLP-1） in pancreatic tissues. The level of cyclic adenosine monophosphate （cAMP） in pancreatic tissue was determined by enzyme-linked immunosorbent assay （ELISA）. ResultCompared with the blank group， the model group had pathological changes in pancreatic tissue， high levels of FBG， GSP， GLU， TC， TG， and LDL-C （P<0.01）， low level of HDL-C （P<0.05）， low protein expression of TGR5， p-PKA （Thr197）/PKA， p-CREB （Ser133）/CREB， PC1/3， and GLP-1 in pancreatic tissue （P<0.01）， and low content of cAMP in the pancreas （P<0.01）. Pancreatic tissue lesion in the treatment groups were milder than that in the model group. Both the high-dose MGQT and metformin can reduce the levels of FBG， GSP， GLU， TC， TG， and LDL-C in db/db mice （P<0.05， P<0.01） and increase the level of HDL-C （P<0.01）. Except the GLP-1 protein in the medium-dose MGQT group， the protein expression of TGR5， p-PKA （Thr197）/PKA， p-CREB （Ser133）/CREB， PC1/3， and GLP-1 in the high-dose and medium-dose MGQT groups and the metformin group increased compared with that in the model group （P<0.05， P<0.01）. The content of cAMP in the pancreatic tissue of the high-dose and medium-dose MGQT groups and the metformin group was raised compared with that in model group （P<0.05， P<0.01）. ConclusionMGQT can improve the glucose homeostasis in db/db mice with T2DM by regulating TGR5/cAMP/GLP-1 signaling pathway-related protein expression.

ObjectiveTo observe the effect of modified Gegen Qinliantang on the expression levels of proteins related to the farnesoid X receptor/small heterodimer partner/peroxisome proliferator-activated receptor α （FXR/SHP/PPARα） signaling pathway in the liver tissue of db/db model mice with type 2 diabetes mellitus （T2DM） and explore the underlying mechanism of action of modified Gegen Qinliantang. MethodThirty db/db mice were randomly divided into model group， metformin group （0.2 g·kg^-1）， and high-， medium-， and low-dose modified Gegen Qinliantang groups （31.9， 19.1， 6.4 g·kg^-1）， with 6 mice in each group. An additional six m/m mice were assigned to the blank group. Respective drugs were administered via oral gavage for 12 weeks. Mouse body weight， fasting blood glucose （FBG）， total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） levels were measured. Oil red O staining was used to observe hepatic lipid accumulation and periodic acid-schiff （PAS） staining was used to assess hepatic glycogen deposition. Ammonium ferric sulfate staining was used to observe cholesterol deposition in intestinal tissues. Western blot was employed to detect the expression of FXR， cholesterol 7α-hydroxylase （CYP7A1）， SHP， and PPARα proteins in liver tissues， and enzyme-linked immunosorbent assay （ELISA） was used to measure serum free fatty acid （FFA） levels. ResultAt the end of the treatment， compared with the blank group， the model group exhibited significant increases in mouse body weight， FBG， FFA， TC， TG， and LDL-C levels （P<0.01）， along with significant hepatic lipid droplets， reduced hepatic glycogen， noticeable cholesterol accumulation in intestinal tissues， significantly decreased expression of FXR， SHP， PPARα proteins， and significantly increased expression of CYP7A1 protein in liver tissues （P<0.01）. Compared with the model group， the metformin group and the high- and medium-dose modified Gegen Qinliantang groups demonstrated significant reductions in mouse body weight， FBG， FFA， TC， TG， LDL-C levels （P<0.05， P<0.01）， significant increases in HDL-C levels （P<0.05， P<0.01）， decreased hepatic lipid accumulation， increased hepatic glycogen， reduced intestinal cholesterol accumulation， significantly increased expression of FXR， SHP， PPARα proteins， and significantly decreased expression of CYP7A1 protein in liver tissues （P<0.01）. ConclusionModified Gegen Qinliantang may regulate the FXR/SHP/PPARα signaling pathway to suppress FFA levels and improve lipid metabolism in T2DM mice.

OBJECTIVE：To systematic ally ev aluate the efficacy and safety of benralizumab in the treatment of severe eosinophilic asthma ，and to provide evidenced-based reference for clinical treatment. METHODS ：Retrieved from PubMed ， Embase，Cochrane Library ，ClinicalTrials.gov，CNKI，VIP and Wanfang database ，randomized controlled trials （RCTs）about benralizumab+routine treatment （trial group ）versus placebo+routine treatment （control group ）were collected during the inception to Dec. 2020. The relevant references were also retrieved manually. After data extraction ，the quality of included literatures was evaluated with bias risk evaluation tool 2.0 recommended by Cochrane systematic evaluator manual 6.1. Meta-analysis was conducted by using Rev Man 5.4 software. RESULTS ：Totally 5 studies involving 2 646 patients were included. Results of Meta-analysis showed that acute exacerbation rate of asthma [RR ＝0.67，95％ CI（0.61，0.74），P＜0.000 01]，asthma control questionnaire score [MD ＝－0.29，95％CI（－0.37，－0.21），P＜0.000 01] and the incidence of severe adverse event [RR ＝0.67，95％CI （0.53，0.84），P＝0.000 6] in trial group were significantly lower than control group. FEV 1[MD＝0.13，95％CI（0.09，0.17），P＜0.000 01] and asthma quality of life questionnaire score [MD ＝0.23，95％CI（0.13，0.33），P＜0.000 01] in trial group were significantly higher than control group. There was no statistical significance in the incidence of adverse event between 2 groups [RR ＝0.97，95％CI （0.92，1.02），P＝0.28]. CONCLUSIONS ：Benralizumab is effective and safe in the treatment of severe eosinophilic asthma. Due to the relatively limited data ，this conclusion needs to be confirmed by more studies.

Objective:By investigating the demand of " Internet-based health education" for urban and rural residents, to identify the main functions of " Internet-based health education" platform and the priority order that platform design should follow, in an effort to help promote the accurate dissemination of health education.Methods:Since April 2019, a stratified random sampling method was used to collect urban and rural residents in 3 counties and cities of a city. The survey mainly investigated the importance of the preliminary function and the specific demand of residents for " Internet-based health education" . With data collected and based on Kano model, the Better-Worse coefficient was used for quantitative analysis.Results:There are 14 main functions of the function item identification and discovery platform; among them, privacy, and without product placement are regarded requisites of the platform, while simple and stable operation among others rank the expected functions. in addition, artistic interface, fun experience, etc. were seen as the undifferentiated functions.Conclusions:The platform design for " Internet-based health education" should follow the priority order of privacy, without product placement, simple and stable operation, information authority, low attrition, comprehensive functions, perfect supervision, free service and high popularity.

Objective:To develop a deep learning model for predicting three-dimensional (3D) voxel-wise dose distributions for intensity-modulated radiotherapy (IMRT).Methods:A total of 110 postoperative rectal cancer cases treated by IMRT were considered in the study, of which 90 cases were randomly selected as the training-validating set and the remaining as the testing set. A 3D deep learning model named 3D U-Res-Net was constructed to predict 3D dose distributions. Three types of 3D matrices from CT images, structure sets and beam configurations were fed into the independent input channel, respectively, and the 3D matrix of IMRT dose distributions was taken as the output to train the 3D model. The obtained 3D model was used to predict new 3D dose distributions. The predicted accuracy was evaluated in two aspects: the average dose prediction bias and mean absolute errors (MAEs)of all voxels within the body, the dice similarity coefficients (DSCs), Hausdorff distance(HD 95) and mean surface distance (MSD) of different isodose surfaces were used to address the spatial correspondence between predicted and clinical delivered 3D dose distributions; the dosimetric index (DI) including homogeneity index, conformity index, V50, V45 for PTV and OARs between predicted and clinical truth were statistically analyzed with the paired-samples t test. Results:For the 20 testing cases, the average prediction bias ranged from -2.12% to 2.88%, and the MAEs varied from 2.55% to 5.75%. The DSCs value was above 0.9 for all isodose surfaces, the average MSD ranged from 0.21 cm to 0.45 cm, and the average HD 95 varied from 0.61 cm to 1.54 cm. There was no statistically significant difference for all DIs, except for bladder Dmean. Conclusions:This study developed a deep learning model based on 3D U-Res-Net by considering beam configurations input and achieved an accurate 3D voxel-wise dose prediction for rectal cancer treated by IMRT.

OBJECTIVE: Cervical cancer is one of the most common malignant tumors. Our previous results showed that long non-coding RNA (lncRNA) XLOC_006390 plays an important role in cervical cancer. In this study, we have explored the mechanism of action of lncRNA XLOC_006390. METHODS: LncRNA XLOC_006390 was proposed to exercise its function as a competing endogenous RNA (ceRNA), and its potential targeted miRNAs was predicted through the database LncBase Predicted v.2. Two miRNAs, miR-331-3p, and miR-338-3p, were chosen for the study. Expression of miRNAs and lncRNA in cervical cancer cells and tissues was detected by reverse transcription polymerase chain reaction. To determine the correlation, silencing of XLOC_006390, over-expression of miR-331-3p, and miR-338-3p was performed in SiHa and Caski cell lines, respectively. RESULTS: Based on the interactive effect between miRNA and lncRNA, miR-331-3p and miR-338-3p were significantly downregulated in cervical cancer cells and tissues, and their expression levels were negatively related to that of lncRNA. Our results also showed that the expression of miR-331-3p target gene NRP2, miR-338-3p target genes PKM2, EYA2 was significantly downregulated when the XLOC_006390 was knocked down. Further, XLOC_006390 was found to facilitate cervical cancer tumorigenesis and metastasis by downregulating miR-331-3p and miR-338-3p expression. CONCLUSION: Taken together, our study demonstrated that XLOC_006390 may serve as a ceRNA and reversely regulates the expression of miR-331-3p and miR-338-3p, thus facilitating cervical cancer tumorigenesis and metastasis.
Carcinogenesis* ; Cell Line ; MicroRNAs ; Neoplasm Metastasis* ; Polymerase Chain Reaction ; Reverse Transcription ; RNA ; RNA, Long Noncoding* ; Uterine Cervical Neoplasms*

Objective To evaluate the diagnostic value of copeptin and cancer antigen 125 (Ca-125) in acute heart failure (AHF) patients with atrial fibrillation, and to explore the relationship between copeptin, Ca-125 and short-term cardiovascular events. Methods A total of 376 patients with acute left heart failure or permanent atrial fibrillation admitted to the Department of Cardiology of First Affiliated Hospital of Nanjing Medical University from January 2016 to January 2018 were enrolled as the study group. According to whether having atrial fibrillation or not, 376 patients were divided into atrial fibrillation group (n = 108), AHF group (n = 134) and AHF with atrial fibrillation group (n = 134). 102 healthy persons in the same period were enrolled as healthy control group. Copeptin, Ca-125, N-terminal pro-brain natriuretic peptide (NT-proBNP) within 24 hours after admission or on the day of physical examination were determined, and cardiac function indexes including left atrial diameter (LAD), left ventricular diameter (LVD) and left ventricular ejection fraction (LVEF) at 1 week after admission or on the day of physical examination were determined. Correlation analysis among above indexes was conducted by Pearson correlation analysis. Receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of copeptin and Ca-125 in AHF with atrial fibrillation. Results Compared with the healthy control group, copeptin, Ca-125, NT-proBNP, LAD, and LVD in atrial fibrillation group, AHF group and AHF with atrial fibrillation group showed a tendency of gradual increase [copeptin (pmol/L): 12.43±4.36, 18.77±5.29, 32.82±7.07 vs. 6.68±1.94; Ca-125 (kU/L): 18.82±7.39, 27.97±11.47, 61.37±25.49 vs. 4.43±1.74; NT-proBNP (ng/L): 1 070.87±428.84, 1 734.13±725.09, 2 745.92±709.91 vs. 570.40±213.87; LAD (mm): 37.24±6.35, 41.31±7.94, 46.24±10.96 vs. 33.29±4.53; LVD (mm): 49.46±5.19, 52.51±8.09, 55.96±6.49 vs. 45.99±6.26, all P < 0.05], and LVEF showed a tendency of gradual decrease (0.52±0.11, 0.46±0.10, 0.41±0.09 vs. 0.57±0.08, all P < 0.05), indicating that the deterioration of all indexes in AHF patients with atrial fibrillation was more obvious. Correlation analysis showed that copeptin was positively correlated with LAD (r = 0.479, P = 0.012) and LVD (r = 0.513, P = 0.005), and it was negatively correlated with LVEF (r = -0.626, P < 0.001). Ca-125 was positively correlated with LAD (r = 0.479, P = 0.011) and LVD (r = 0.513, P = 0.028), and it was negatively correlated with LVEF (r = -0.645, P = 0.019). ROC curve analysis showed that the area under ROC curve (AUC) of copeptin, Ca-125, NT-proBNP and copeptin combined with Ca-125 in the diagnosis of AHF with atrial fibrillation was 0.750, 0.623, 0.647 and 0.842, respectively, with diagnostic value on AHF with atrial fibrillation. The diagnostic value of copeptin combined with Ca-125 was the largest, with a sensitivity of 72.64% and a specificity of 92.47%. Compared with the healthy control group, the incidence of cardiovascular events after 3 months of follow-up in the atrial fibrillation group, AHF group and AHF with atrial fibrillation group was significantly increased [6.5% (7/108), 9.0% (12/134), 30.6% (41/134) vs. 1.0% (1/102), χ2 = 56.574, P = 0.000], indicating that patients with AHF and atrial fibrillation were more likely to have cardiovascular events. Copeptin combined with Ca-125 showed a significant positive correlation with short-term cardiovascular events (r = 0.641, P = 0.004). Conclusions The combination of copeptin and Ca-125 has a higher diagnostic accuracy for AHF patients with atrial fibrillation. Copeptin and Ca-125 were positively correlated with short-term cardiovascular events. It may be used to assess the prognosis of AHF patients with atrial fibrillation.