Wnt/β-catenin signaling pathway is highly conserved in evolution,which involves in the regulation of a variety of biological processes such as embryonic growth,development,energy metabolism and stem cells maintenance.Aberrant activation of Wnt/β-catenin signaling pathway has a closely relationship with tumorigenesis.Investigating the role of Wnt/β-catenin signaling in glioma cell proliferation,invasion,apoptosis and tumor angiogenesis will provide novel therapeutic targets and intervening measures for glioma treatment.

Objective To preliminarily explore the effects of human microRNA-181a on migration of gastric cancer cells and its mechanism.Methods The expression of miRNA-181a-5p in gastric cancer cell line GC9811 and peritoneal high metastasis gastric cancer cell line GC9811-P were tested by quantitative real-time polymerase chain reaction (qRT-PCR ). GC9811 cell line was transfected byendogenous synthetic analog mimic and its homologous negative control of miRNA-181a-5p,which were considered as up-regulated group and its control group respectively;GC9811-P were transfected by miRNA inhibitor and its homologous negative control of miRNA-181a-5p,which were considered as down-regulated group and its control group respectively.After miRNA-181a-5p was up or down-regulated,cell proliferation,migration and apoptosis capabilities of gastric cells were detected by matrix thiazolyl tetrazollium (MTT)assay,cloning-forming assay,Transwell migration test,wound healing assays and apoptosis test.After miRNA-181a-5p was up or down regulated,the changes of matrix metalloproteinase (MMP)14 expression were determined by Western blot.Independent sample t test was performed for mean comparison between samples and chi square test was used for rate comparison.Results The results of qRT-PCR showed the relative expression quantity of miRNA-181a-5p in GC9811 was 1 .000 00 ± 0.021 26 and in GC9811-P was 3.175 61 ±0.106 76,and the difference was statistically significant (t =34.620,P <0.01 ).The results of MTT assay indicated that the cell proliferation rate of up-regulated group was higher than that of up-regulated control group,and that of down-regulated group was lower than down-regulated control group.The cloning-forming assay demonstrated that the number of clone forming and clone forming rate of up-regulated group,up-regulated control group,down-regulated group and down-regulated control group were 234.00±10.12 and 46.8%,93.00±9.61 and 18.6%,51 .00 ±7.96 and 10.2%,99.00±8.05 and 19.8%,respectively.The differences between up-regulated group,down-regulated group and their control group were statistically significant (t = 17.500,7.344,χ2 = 12.27, 9.51 ,all P <0.01).The results of Transwell migration experiment showed the number of cells migrated through membrane hole of up-regulated group was 164.00±19.31 ,and which was higher than that of up-regulated control group (87.00±23.04,t=4.436,P <0.05);that of down-regulated group was 157.00± 11 .50,and which was lower than that of down-regulated control group (234.00 ±12.12,t =7.982,P <0.05).The result of wound healing assays indicated that the rate of migration distance of up-regulated group,up-regulated control group,down-regulated group and down-regulated control group were 2.09 ± 0.18,1 .27 ±0.23,1 .15 ±0.15 and 1 .67 ±0.12,respectively.The differences between up-regulated group,down-regulated group and their control group were statistically significant (t =4.863 and 4.689, both P <0.05).The results of apoptosis experiments demonstrated that the apoptosis rate of up-regulated group,up-regulated control group,down-regulated group and down-regulated control group were (6.10± 1 .02 )%,(9.10 ± 2.13 )%,(12.70 ± 1 .23 )%,(8.70 ± 2.54 )%,respectively,and there was no statistically significant difference between up-regulated group,down-regulated group and their control group (both P *0.05).The results of Western blot showed that the grey value of up-regulated group was 561 .881 ±35 .740,which was higher than that of up-regulated control group (275 .784±23.520);that of down-regulated group was 579.565 ±37.950,which was lower than that of down-regulated control group (1 312.760±51 .270),and the differnces were statistically significant (t =11 .580 and 19.910,both P <0.01).Conclusion miRNA-181a-5p highly expresses in peritoneal high metastasis gastric cancer cell line GC9811-P and promoted the proliferation and migration of gastric cancer cell line GC9811 and GC9811-P with a tendency to suppress apoptosis.

Objective To analyze the massive explosions and burn at Tianjin Port in 2015 resulted in a mass casualty event,and the entire course of response of a hospital to deal with such major sudden accident in order to find a rational strategy for optimal use of medical resources and reduce the critical mortality.Methods This study was done by a retrospective analysis of data from one trauma center at an academic hospital.Data including outcome,triage,severity and pattern of injuries,patient flow,and medical resources used were obtained by the review of hospital records.Results This disaster caused 165 deaths,8 missing contact,and 797 non-fatal casualties.The Pingjin Hospital admitted 298 casualties,and 29 of them were seriously injured referred to by Tianjin Emergency Medical Center.Excessive triage rate made after transfer to another hospital was 62.07% with 11 of the 29 severely injured patients.Maximum (also the first)surge had 147 injured patients arrived around one hour after incident,the second surge had 31 seriously injured patients occurred around 4 hours after incident.Of them,17 patients needed surgery and 17 patients were admitted to the intensive care unit.Conclusions These data showed that the number of casualties in the first surge was substantially larger than predicted and those casualties had less severe trauma,whereas the number of the injured in the second surge was less but the trauma was more severe.In order to maintain the hospital surge capacity,an effective re-triage and a hospital-wide damage control principle can be used to deal with.

Objective To investigate the relationship between the expression of NOD-like receptor protein 3 (NLRP3) inflammasome in colonic mucosal tissues of ulcerative colitis (UC) patients and UC mice model and the activity of UC.Methods From December 2016 to January 2018,at Department of Gastroenterology,the First Affiliated Hospital of Zhejiang Traditional Chinese Medicine University,60 patients with UC were recruited,of which 15 cases at remission phase,15 cases at mild activity phase,and 15 cases at moderate activity phase,and 15 cases at severe activity phase;and 15 healthy subjects were selected as healthy control group.UC mice models were established by dextran sulfate sodium (DSS).Forty-eight BALB/c mice were divided into 2.5％ DSS group,5.0％ DSS group and 7.5％ DSS group and control group.The colon tissues of UC patients and UC mice models were pathologically scored.The expression of NLRP3,cysteinyl aspartate specific proteinase 1 (caspase-1) and apoptosis-associated speck-like protein containing CARD (ASC)at mRNA level in colon tissues of UC patients and UC mice models were determined by real time fluorescence quantitative polymerase chain reaction (PCR).The expression of NLRP3,caspase-1 and ASC at protein level in colon tissues of UC patients and UC mice models were detected by Western blotting.One-way analysis of variance and SNK-t test were performed for statistical analysis.Results The histopathological scores of colon tissues of UC patients at remission phase,at mild activity phase,at moderate activity phase,at severe activity phase and healthy controls were 2.37 ± 0.46,4.84 ± 1.29,6.82 ± 0.96,9.42 ± 1.13 and 1.23 ± 0.55,respectively;the differences were statistically significant (F =67.68,P ＜ 0.01).The higher the degree of inflammation,the higher the pathological score,and the differences were statistically significant (all P ＜ 0.05).The pathological scores of colon tissues of mice in the 2.5％ DSS group,5.0％ DSS group and 7.5％ DSS group were 4.54±0.74,6.02± 1.00 and 8.43 ± 1.46,respectively;the higher the dose of DSS,the higher the pathological score,and the differences were statistically significant (all P ＜ 0.05).The expression of NLRP3 at mRNA level of UC at remission phase,mild activity phase,moderate activity phase,severe activity phase and healthy controls were 1.15 ±0.10,1.49 ±0.13,2.00±0.25,2.05 ±0.33 and 0.61 ±0.09,respectively;the expression ofcaspase-1 at mRNA level were 1.13 ±0.08,1.51 ±0.19,2.10 ±0.23,2.88 ±0.33 and 0.61 ±0.11,respectively;the expression of ASC at mRNA level were 1.12 ± 0.08,1.88 ± 0.33,2.53 ± 0.22,3.20 ± 0.24 and 0.59 ± 0.12,respectively;the differences between groups were statistically significant (F =108.43,63.25 and 105.25,all P ＜ 0.01).The higher the degree of inflammation,the higher the mRNAexpression levels of NLRP3,caspase-1 and ASC,and the differences were statistically significant (all P ＜0.01).The higher the dose of DSS,the higher the protein expression levels of NLRP3,caspase-1 and ASC at mRNA level.The higher the degree of inflammation,the higher expression of NLRP3,caspase-1 and ASC in colon tissues of UC patients.The higher dose of DSS,the higher the protein expression levels of NLRP3,caspase-1 and ASC in colon tissues of mice.Conclusions The expression level of NLRP3 inflammasome is different in different stages of UC,the higher degree of inflammatory activity,the higher the expressie level.It is helpful to evaluate the activity of UC by detecting the expression level of NLRP3 inflammasome.

Aptamers are DNA or RNA fragments that can specifically bind to target substances.Because of the excellent properties such as strong binding force,high specificity,small physical size,chemical synthesis and modification,good biocompatibility,and low immunogenicity aptamers show wide application propects in biomedical researches.Aptamers can also bind specifically to receptors on the surface of cell membranes,and mediate the endocytosis of nanoparticles into cells,making them ideal drug targeting ligands.Organic nanomaterials have excellent application value in nanodrug delivery system because of their good biocompatibility and degradability.In this paper,the recent research progress of aptamers and organic nanomaterials drug delivery systems was reviewed.

Objective: To investigate the efficacy and safety of rapamycin in children with tuberous sclerosis complex (TSC) associated renal disease. Methods: A prospective self-control study was conducted. The clinical data of 92 children diagnosed with tuberous sclerosis complex associated kidney disease at the People′s Liberation Army General Hospital from January 2011 to January 2019 were collected. The long-term rapamycin treatment for all patients initiated at 1 mg/(m²·d), which was gradually adjusted to reach a blood concentration of 5-10 μg/L. The changes of the maximum diameter of renal lesions in children after rapamycin treatment were observed and analyzed with Wilcoxon test. Results: Ninety-two children, including 52 males and 40 females, who met the criteria were analyzed. Sixty patients had only renal angiomyolipoma(RAML), while 24 patients had only multiple renal cysts(MRC), and 8 patients had both lesions. The age of TSC diagnosis was 16.0 (7.0, 42.0) months, and the age of initial treatment with rapamycin was 63.5 (21.0, 103.0) months. The follow-up lasted for 12.0 (4.0, 23.0) months. Sequencing of TSC1 and TSC2 genes was performed in 54 children with TSC, including 3 patients (6%) with mutations in TSC1 gene and 51 patients (94%) with mutations in TSC2 gene. The maximum RAML diameter before treatment was 7.0 (4.0, 9.0) mm. The best effect reached at 3 months of treatment, with the diameter of 4.0 (0,7.0) mm. The maximum diameters at 6 months, 1 year and 1-2 years were 5.0 (0,9.8) mm, 5.0 (1.5, 8.5) mm, 5.5 (3.0, 9.0) mm, respectively, and were significantly different from the baseline (Z=-2.404,-2.350,-2.750,P=0.016,0.019,0.006, respectively). The maximum diameter after 2-3 years, and ≥3 years were 5.0 (3.9,7.0) mm and 6.0 (1.0, 11.0) mm, without significant difference from the baseline (Z=-0.856,-0.102,P=0.393,0.919, respectively).The maximum diameters of MRC after 3 months, 6 months, 1 year,1-2 years, 2-3 years, and ≥3 years were 11.0 (5.0, 14.0) mm,3.0 (0.0,11.0) mm,5.0 (0,21.0) mm,0 (0,14.0) mm,0 (0,10.0) mm, and 0 (0,18.3) mm, respectively, but were not significantly different rom the baseline (7.0 (5.0, 15.7) mm)(Z=-0.944,-1.214,-1.035,-1.896,-1.603,-1.214,P=0.345,0.225,0.301,0.058,0.109,0.225, respectively).Twenty-nine patients (32%) had oral ulcers during the entire treatment period, and no serious adverse reactions were observed. Conclusions Rapamycin could decrease the diameter of TSC-related RAML, but could not inhibit the growth of cysts. It is well tolerated in the treatment of renal diseases associated with tuberous sclerosis complex.

Epilepsy is a common disease in central nervous system;most patients with epilepsy after regular anti-epilepsy drug treatment can be controlled,but drug treatment in about 20％-30％ of patients is invalid,known as refractory epilepsy.With the development of imaging techniques,PET/MRI emerge and they combine anatomical and functional imaging,which makes the imaging more clear,enjoying more accurate anatomical structure.Thus,PET/MRIplay important roles in the process of pathogenesis,diagnosis and preoperative assessment of epilepsy.We mainly introduce the concepts of PET/MRIand the comparison with other imaging technology,and describe the application of PET/MRI in preoperative assessment ofrefractory epilepsy.

Objective:To investigate the epidemiological characteristics of lower extremity deep vein thrombosis (DVT) in patients with femoral fracture.Methods:Retrospectively analyzed were the data of 2,571 patients with femoral fracture who had been treated at the Third Hospital of Hebei Medical University from January 2019 to December 2019. There were 1,079 males and 1,492 females, aged from 14 to 96 years (average, 67.1 years). There were 1,158 femoral neck fractures, 951 femoral intertrochanteric fractures, 309 femoral shaft fractures, and 153 femoral condylar fractures. 2,414 patients were treated surgically while 157 patients non-surgically. Color Doppler ultrasonography of both lower extremities was performed to determine the occurrence of DVT before operation and every week after operation for patients undergoing surgical treatment, and within 48 hours after admission and every week during hospitalization for those undergoing non-surgical treatment. The incidence and location of DVT were recorded for different femoral fractures.Results:The incidence of DVT in this cohort was 35.5%(913/2,517), that of proximal DVT 5.3%(135/2,571), and that of distal DVT 30.3% (778/2,571). In patients with femoral neck fracture, femoral intertrochanteric fracture, femoral shaft fracture and femoral condylar fracture, the incidence of DVT was respectively 28.8% (334/1,158), 44.7% (425/951), 30.7% (95/309) and 38.6% (59/153), the incidence of proximal DVT was respectively 2.7% (31/1,158), 5.6%(53/951), 9.7% (30/309) and 13.7% (21/153), and the incidence of distal DVT was respectively 26.2% (303/1,158), 39.1% (372/951), 21.0% (65/309) and 24.8%(38/153). The incidence of DVT in the femoral vein and above, popliteal vein, tibiofibular vein and intermuscular vein in this cohort was respectively 2.3%(60/2,571), 2.9%(75/2,571), 6.4%(165/2,571) and 23.8%(613/2,571).Conclusions:The incidence of DVT may be high in patients with femoral fracture, and the proximal DVT with a high risk of pulmonary embolism may occur more in patients with femoral condylar fracture.

OBJECTIVE To assess the long-term cost-effectiveness of five glucagon-like peptide-1 receptor agonists （GLP- 1RAs） in the treatment of poorly controlled type 2 diabetes mellitus （T2DM） treated with metformin. METHODS Baseline data from patients in previously published meta-analysis and included randomized controlled trials （RCTs） were extracted to predict survival， long-term efficacy， and costs for each group using the United Kingdom prospective diabetes study outcome model 2.1. The cost-effectiveness of 5 GLP-1RAs （liraglutide， lixisenatide， exenatide， dulaglutide， and semaglutide） was analyzed by cost- utility analysis. Sensitivity analysis and scenario analysis were also performed to verify the uncertainty of basic analysis results. RESULTS A total of 21 RCTs with 6 796 patients were included. Survival analysis curves showed the superiority of semaglutide in reducing the risk of death from cardiovascular disease and dulaglutide in reducing the risk of all-cause mortality over other GLP- 1RAs. The cost-utility analysis showed that the five drugs were economically superior to inferior in the order of lixisenatide， semaglutide， exenatide， dulaglutide， and liraglutide； one-way and probabilistic sensitivity analyses indicated that the results were robust. The scenario analysis results indicated that the price of semaglutide should decrease by at least 54.64% to 369.21 yuan， which is cost-effectiveness compared to lixisenatide. CONCLUSIONS For T2DM patients in China with poor glycemic control after treatment with metformin， lixisenatide and semaglutide may be considered as the preferred regimen.

OBJECTIVE To evaluate the cost-effectiveness of tislelizumab combined with chemotherapy as first-line treatment for locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma. METHODS The data of RATIONALE-305 study and related literature were used to establish a partitioned survival model from the perspective of China’s health system. The cycle was 3 weeks， the simulation time was set as 10 years， and the discount rate was 5%. The quality-adjusted life years （QALYs） were used as the health outcome indicator to evaluate the cost-effectiveness of tislelizumab combined with chemotherapy versus placebo combined with chemotherapy as first-line treatment for locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma， and one-way sensitivity analysis and probabilistic sensitivity analysis were also conducted. RESULTS The base analysis showed that the patients received more 0.268 QALYs with tislelizumab plus chemotherapy， compared with placebo plus chemotherapy， but the cost increased by 70 404.81 yuan with an incremental cost- effectiveness ratio （ICER） of 262 431.62 yuan/QALY， which was less than three times China’s gross domestic product （GDP） per capita in 2023 as the willingness-to-pay （WTP） threshold （268 074 yuan/QALY）. One-way sensitivity analysis showed that the efficacy value of progress free survive and the price of tislelizumab had a greater impact on the ICER value. The results of probability sensitivity analysis showed that when the WTP threshold was 3 times China’s GDP per capita in 2023， the probability of tislelizumab being cost-effective was 53.3%. CONCLUSIONS When the WTP threshold is 3 times China’s GDP per capita in 2023， tislelizumab plus chemotherapy is cost-effective for first-line treatment of locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma， compared with placebo plus chemotherapy.