Objective To investigate the potential mechanism of tumor-derived exosome miR-3173-5p promoting the activation of cancer-associated fibroblasts(CAFs)and regulating the proliferation,invasion and apoptosis of non-small cell lung cancer(NSCLC)cells.Methods Exosome(Exo)of NSCLC cell A549 was extracted,the morphology of Exo was observed by transmission electron microscopy,and the expression of Exo marker protein was detected by Western blot.Real-time quantitative fluorescent PCR(qRT-PCR)was used to detect the expression of miR-3173-5p in A549 cells and Exo.The binding of miR-3173-5p to F-box/WD-40 domain protein11(FBXW11)was predicted by Starbase database,and verified by luciferase reporter gene analysis.Human lung fibroblast cell line(MRC-5)was treated with Exo and Exo inhibitor GW4869 or NC inhibitor/mimic or miR-3173-5p inhibitor/mimic and/or FBXW11 overexpression/empty vector,NC group,Exo group,Exo+GW4869 group,Exo-NC inhibitor group,Exo-miR-3173-5p inhibitor group,Exo-NC mimic group,Exo-miR-3173-5p mimic group,Exo-miR-3173-5p mimic+Vector group and Exo-miR-3173-5p mimic+FBXW11 group were set up respectively.The level of CAFs marker protein[Matrix metalloproteinase-9(MMP-9),α-Smooth muscle aorta(α-SMA),Chemokine(C-X-C motif)ligand 12(CXCL12),Fibronectin,Vimentin,Interleukin-1β(IL-1β),Interleukin-6(IL-6),Interleukin-8(IL-8)]in cells of each group was detected by Western blot analysis,and the influence of exosome miR-3173-5p and FBXW11 expression on CAFs activation was analyzed.Exo and Exo-miR-3173-5P mimic were separated and the supernatant of MRC-5 cells incubated with Exo-FBXW11 was used as conditioned medium(CM)to culture A549 cells.The NC-CM group,Exo-CM group,Exo-miR-3173-5p mimic-CM group and Exo-FBXW11-CM group were set up respectively.MTT assay,Transwell assay and flow cytometry were used to detect the effects of CAFs activation on proliferation,invasion and apoptosis of NSCLC cells.Results Transmission electron microscopy showed that the diameter of exosomal vesicles derived from NSCLC cells was about 30～100 nm.Western blot analysis showed that all exosome labeled proteins were positive.The expression of miR-3173-5p(33.45±3.16)in NSCLC-derived exosomes was significantly higher than that in tumor cells(1.01±0.07),and the difference was statistically significant(t=1.263,P<0.001).MiR-3173-5p targets FBXW11 and inhibits its expression.Compared with NC group,CAFs marker protein levels in Exo group were significantly increased(t=12.214～24.908),the expression of CAFs marker protein in Exo+GW4869 group was significantly inhibited compared with Exo group(t=13.160～25.143),the differences were statistically significant(all P<0.01),respetively.Compared with Exo group,miR-3173-5p inhibitor inhibited EXO-induced CAFs marker protein expression(t=11.059～21.094),and miR-3173-5p mimic promoted the expression of CAFs marker protein(t=12.943～18.671),the differences were statistically significant(all P<0.01),respectively.Overexpression of FBXW11 reversed the induction of CAFs activation by miR-3173-5p mimic.Compared with the NC-CM group,the proliferation activity and invasion rate of A549 cells in the Exo-CM group were significantly enhanced,and the apoptosis rate was significantly inhibited(t=10.207,2.359,3.001),miR-3173-5p mimic enhanced the promoting effect of Exo-CM on proliferation and invasion of A549 cells and the inhibitory effect on apoptosis(t=9.399,3.438,3.208),while overexpression of FBXW11 can antagonize the promotion effect of Exo-CM on proliferation and invasion of A549 cells and the inhibition effect on apoptosis(t=18.868,7.070,9.813),the differences were statistically significant(all P<0.05),respectively.Conclusion Tumor-derived exosome miR-3173-5p promotes CAFs activation through targeted inhibition of FBXW11 expression,further promotes proliferation and invasion of NSCLC cells,inhibits cell apoptosis,and regulates the occurrence and development of NSCLC.

Objective To investigate the potential mechanism of tumor-derived exosome miR-3173-5p promoting the activation of cancer-associated fibroblasts(CAFs)and regulating the proliferation,invasion and apoptosis of non-small cell lung cancer(NSCLC)cells.Methods Exosome(Exo)of NSCLC cell A549 was extracted,the morphology of Exo was observed by transmission electron microscopy,and the expression of Exo marker protein was detected by Western blot.Real-time quantitative fluorescent PCR(qRT-PCR)was used to detect the expression of miR-3173-5p in A549 cells and Exo.The binding of miR-3173-5p to F-box/WD-40 domain protein11(FBXW11)was predicted by Starbase database,and verified by luciferase reporter gene analysis.Human lung fibroblast cell line(MRC-5)was treated with Exo and Exo inhibitor GW4869 or NC inhibitor/mimic or miR-3173-5p inhibitor/mimic and/or FBXW11 overexpression/empty vector,NC group,Exo group,Exo+GW4869 group,Exo-NC inhibitor group,Exo-miR-3173-5p inhibitor group,Exo-NC mimic group,Exo-miR-3173-5p mimic group,Exo-miR-3173-5p mimic+Vector group and Exo-miR-3173-5p mimic+FBXW11 group were set up respectively.The level of CAFs marker protein[Matrix metalloproteinase-9(MMP-9),α-Smooth muscle aorta(α-SMA),Chemokine(C-X-C motif)ligand 12(CXCL12),Fibronectin,Vimentin,Interleukin-1β(IL-1β),Interleukin-6(IL-6),Interleukin-8(IL-8)]in cells of each group was detected by Western blot analysis,and the influence of exosome miR-3173-5p and FBXW11 expression on CAFs activation was analyzed.Exo and Exo-miR-3173-5P mimic were separated and the supernatant of MRC-5 cells incubated with Exo-FBXW11 was used as conditioned medium(CM)to culture A549 cells.The NC-CM group,Exo-CM group,Exo-miR-3173-5p mimic-CM group and Exo-FBXW11-CM group were set up respectively.MTT assay,Transwell assay and flow cytometry were used to detect the effects of CAFs activation on proliferation,invasion and apoptosis of NSCLC cells.Results Transmission electron microscopy showed that the diameter of exosomal vesicles derived from NSCLC cells was about 30～100 nm.Western blot analysis showed that all exosome labeled proteins were positive.The expression of miR-3173-5p(33.45±3.16)in NSCLC-derived exosomes was significantly higher than that in tumor cells(1.01±0.07),and the difference was statistically significant(t=1.263,P<0.001).MiR-3173-5p targets FBXW11 and inhibits its expression.Compared with NC group,CAFs marker protein levels in Exo group were significantly increased(t=12.214～24.908),the expression of CAFs marker protein in Exo+GW4869 group was significantly inhibited compared with Exo group(t=13.160～25.143),the differences were statistically significant(all P<0.01),respetively.Compared with Exo group,miR-3173-5p inhibitor inhibited EXO-induced CAFs marker protein expression(t=11.059～21.094),and miR-3173-5p mimic promoted the expression of CAFs marker protein(t=12.943～18.671),the differences were statistically significant(all P<0.01),respectively.Overexpression of FBXW11 reversed the induction of CAFs activation by miR-3173-5p mimic.Compared with the NC-CM group,the proliferation activity and invasion rate of A549 cells in the Exo-CM group were significantly enhanced,and the apoptosis rate was significantly inhibited(t=10.207,2.359,3.001),miR-3173-5p mimic enhanced the promoting effect of Exo-CM on proliferation and invasion of A549 cells and the inhibitory effect on apoptosis(t=9.399,3.438,3.208),while overexpression of FBXW11 can antagonize the promotion effect of Exo-CM on proliferation and invasion of A549 cells and the inhibition effect on apoptosis(t=18.868,7.070,9.813),the differences were statistically significant(all P<0.05),respectively.Conclusion Tumor-derived exosome miR-3173-5p promotes CAFs activation through targeted inhibition of FBXW11 expression,further promotes proliferation and invasion of NSCLC cells,inhibits cell apoptosis,and regulates the occurrence and development of NSCLC.

Objective To investigate the articles on liver diseases published by authors from China (excluding Hong Kong, Macao, and Taiwan regions) in Gastroenterology & Hepatology journals indexed in Science Citation Index Expanded (SCIE) in 2016-2020, to analyze the bibliographic and citation data of these articles, and to understand the contribution and impact of Chinese scholars in the field of liver disease research in recent years. Methods The data for bibliometric analysis came from the SCIE database and Journal Citation Reports (JCR). The SCIE database was searched for the journal articles published in JCR Gastroenterology & Hepatology journals in 2016-2020, with a title or abstract containing "Liver", "Hepatocellular", "Hepatitis", "Cirrhosis", or "Hepatic" and a publication type of Article. Clinical guidelines were excluded, and the records with the corresponding author's affiliation containing institutions in China (excluding Hong Kong, Macao, and Taiwan regions) were screened out. R package bibliometrix was used to calculate the frequency of citations of included articles by liver disease studies published by Chinese and global authors in the Gastroenterology & Hepatology journals in 2016-2020, and R package DescTools was used to perform the Cochran-Armitage trend test to observe the change in composition ratio. Results In the Q1 Gastroenterology & Hepatology journals in 2016-2020, liver disease studies published by Chinese authors accounted for 9.5%. In recent years, the proportion of liver disease studies published by Chinese authors in Q1 Gastroenterology & Hepatology journals continues to increase from 6.0% to 12.2% ( P < 0.001). Among the liver disease studies published by Chinese authors in Q1 Gastroenterology & Hepatology journals, 79.7% were funded by National Natural Science Foundation of China, and there was no significant change in the proportion of studies funded by National Natural Science Foundation of China and published by Chinese authors in each partition of Gastroenterology & Hepatology journals in 2016-2020. The frequency of citations of included articles by liver disease studies published by Chinese and global authors in the Gastroenterology & Hepatology journals showed that liver disease studies published by Chinese authors had a high impact in both domestic and international academic communities. Conclusion In recent years, there has been a constant increase in the number of liver disease studies published by Chinese authors in high-impact Gastroenterology & Hepatology journals indexed in SCIE, and most of these studies have been funded by National Natural Science Foundation of China. The liver disease studies published by Chinese authors in Gastroenterology & Hepatology journals have been widely recognized by domestic and international academic communities.

Objective To evaluate the change of clinicopathological features and prognosis of papillary thyroid cancer over a 15-year period.Methods The clinicopathological features and outcomes of papillary thyroid cancer patients were analyzed in three groups according to the time of diagnosis:group Ⅰ (1997-2001),group Ⅱ (2002-2006),and group Ⅲ (2007-2011).Results As time advanced,the average age of papillary thyroid cancer patients increased,tumor stage,like size,extrathyroid invasion and lymph node metastasis decreased dramatically (P ＜ 0.01).The percentage of multifocality and bilaterality increased.The long-term follow up data (median follow up time was 6.6 years),indicated that the 15-year over all survival was 97.8％ and the 15-year disease-free survival was 90.2％.Tumor ≥3 cm,bilaterality,extrathyroid invasion,lymph node metastasis and AJCC stage were correlated with tumor recurrence.By multivariate COX-regression analysis only lymph node metastasis and bilaterality were independent risk factors.Conclusion The clinicopathological features of papillary thyroid cancer changed over 15 years,with the percentage of early-staged patients increased.Lymph node metastasis and bilaterality are two risk factors for tumor recurrence.

Objective To analyze the characteristics of left ventricular systolic function in Kawasaki disease (KD) patients with intravenous immunoglobulin (IVIG) resistant during acute phase by two-dimensional speckle tracking imaging (2D STI).Methods IVIG resistant patients (n=40) as well as age and gender matched IVIG responder patients (n=40) were selected from KD patients in acute phase.Patients in IVIG resistant group were further divided into coronary artery dilation (CAD) subgroup and no coronary artery dilation (NCAD) subgroup.Then conventional echocardiography,2D STI and laboratory indexes were acquired and compared between IVIG resistant group and IVIG responder group,as well as between CAD and NCAD subgroup.ROC curve analysis was used to determine threshold values of 2D STI measurements associated with IVIG resistance.Results Compared with IVIG responder group,coronary artery dilation,left ventricular mass and left ventricular mass index increased,systolic global longitudinal strain (GLS) and systolic global circumferential strain (GCS) decreased,albumin,erythrocyte sedimentation rate,C-reactive protein and platelet increased in IVIG resistant group (all P＜0.05).Taking absolute GLS 16.8％ as a threshold,the area under curve (AUC) was 0.769 (P=0.021),sensitivity,specificity in diagnosis of IVIG resistant was 79.27％,68.36％.Taking absolute GCS 15.9％ as a threshold,AUC was 0.749 (P=0.038),sensitivity,specificity in diagnosis of IVIG resistant was 71.43％,57.28％.Conclusion IVIG resistant KD patients present significantly greater systolic dysfunction compared with responders in patients with KD,which may be the results of myocardium infection other than coronary artery lesions.2D STI may predict myocardial injury in IVIG resistant KD patients.

Objective To explore the distribution change and antimicrobial resistance of pathogens causing catheter associat‐ed urinary tract infection in ICU .Methods 500 cases of patients received by emergency department ICU in our hospital from 2012 April~ 2014 June were collected ,urine samples were collected by closed drainage bag after indwelling catheter in 3 ,7 ,14 ,21ds .By culture ,separation ,purification ,screening and identification and antimicrobial disc diffusion experiments ,distribution changes and resistantance of pathogens causing catheter related infections were analyzed .Results 358 strains were found in catheter associated urinary tract infections ,in which 175 strains were Gram‐positive bacteria ,mainly were Staphylococcus aureus (48 .57% ) and en‐terococci (46 .86% ) ,137 were Gram‐negative bacteria ,mainly were E .coli (56 .93% ) ,46 fungi ,mainly were Candida albicans (47 .83% );Gram‐positive bacteria showed a decreasing trend ,while Gram‐negative bacteria increased every year;resistance rates of Staphylococcus aureus and enterococci to penicillins ,cephalosporins and quinolones were more than 50% ;Escherichia coli and Kleb‐siella pneumoniae had strong resistance to penicillins ,cephalosporins and quinolones ;resistance rate of Pseudomonas aeruginosa to ampicillin ,sulbactam and ampicillin cefazolin up to 100% .Conclusion Escherichia coli is the major pathogens causing ICU catheter associated urinary tract infections;pathogens resistance are strong ,clinical monitoring should be strengthened .

BACKGROUND:The biological substances fixed onto the implant surface, including specific proteins, enzymes, polypeptides, could promote the proliferation and differentiation of osteogenic cells in order to achieve a good osteogenic effect.
OBJECTIVE:To introduce the biological characteristics of the arginine-glycine-aspartic acid (RGD) peptides, cellbiological behavior and implant osseointegration in osteoporosis.
METHODS:Authors retrieved the relevant articles in PubMed database (January 1984 to January 2013), Wanfang database (January 2002 to December 2012) and CHKD database (January 2002 to December 2012) using the key words“RGD peptides, osteoporosis, bone marrow mesenchymal stem cells, osseointegration, osteoblast, induced differentiation”. Papers were included concerning the biological characteristics of RGD peptides, the biological behavior of cells and the bone-implant integration in osteoporosis.
RESULTS AND CONCLUSION:Osseointegration on the surface between implant and bone tissue can be further improved by grafting biological y active substance. Bionics modification, to simulate the extracellular matrix environment in vivo, can promote celladhesion and growth, which is an effective way to improve osseointegration and is also an important direction of research in the field of tissue engineering recently. The future research is focused on designing specific and efficient polypeptides and simple and effective fixation methods.

ObjectiveTo evaluate the efficacy and safety profiles of enteeavir (ETV) in patients with advanced schistosomiasis and hepatitis B virus (HBV) co-infection.Methods Totally sixty patients with advanced schistosomiasis and HBV co-infection were enrolled in this study.The patients were divided into ETV treatment group (n=30) and rhubarb treatment group who refused to receive antiviral treatment (n=30).The patients were treated with ETV or rhubarb thelepus ball on the basis of routine supportive therapy for 52 weeks.The hepatic fibrosis markers (e.g.hyaluronic acid,type Ⅲ procollagen,type Ⅳ collagen,laminin and fibronectin),alanine transaminase (ALT),HBV DNA,Child-Pugh score between two groups were compared.Intention to treat (ITT) population was used for analysis.The measurement data and the enumeration data were analyzed by t test and x2 test,respectively.ResultsAfter 52-week treatment,the hepatic fibrosis markers (hyaluronic acid,type Ⅲ procollagen,type Ⅳ collagen,laminin and fibronectin) were significantly improved in ETV treatment group compared to the rhubarb treatment group (t =3.952,3.765,3.857,3.122 and 3.735,respectively; all P＜0.05),and the fibrosis of liver tissue in ETV treatment group was significantly improved compared with rhubarb treatment group (x2 =11.207,P＜0.05).The ALT level,HBV DNA,Child-Pugh score after 52-weeks treatment in ETV treatment group were statistically reduced compared with rhubarb treatment group (t =3.287,4.382 and 3.872,respectively; all P＜0.05),meanwhile,the ALT normalization rate and HBV DNA undetectable rate were significantly increased in ETV treatment group (x2 =17.376 and 39.095,respectively; both P＜0.05).In addition,no obvious adverse reaction was observed during ETV treatment.Conclusion Entecavir is safe and effective in patients with advanced schistosomiasis and HBV co-infection.

Objective To assess the preventive effect of artesunate against reinfection of Schistosoma japonicum.Methods Volunteers were divided into 3 groups,Medication Group Ⅰ took artesunate 6 mg/kg ,once a week for 4 weeks,Medication Group Ⅱ took artesunate 6 mg/kg in the 1st and 3rd week,twice a week,and a control group was given a placebo.The 3 teams took praziquantel 40 mg/kg on the 4th weekend.The effects of artesunate in early treatment were observed at the 8th weekend,and the preventive effects of artesunate against reinfection were assessed at the 12th weekend.The positive rate of fecal examination was used as the indicator.Results In the stage of early treatment,the positive rates of fecal examination in Medication Group Ⅰ ,Ⅱdecreased significantly compared with the data before the study with all P values less than 0.05 ;in the stage of preventing reinfection,compared with the data before the study,the positive rates of the fecal examination declined significantly in Medication Group Ⅰ,Ⅱ ,with all P values less than 0.05.While in the control group,the positive rates of the fecal examination had no significant changes in the two stages.Conclusions Artesunate has a valid effect against schistosome infections in the early treatment and can prevent residents from reinfection,and the suitable dosage is 6 mg/kg,once a week for 4 weeks.

Objective To evaluate the management of biliary complications (BC) following orthotopic liver transplantation (OLT). Methods From Feb 1999 to Feb 2004, 236 cases underwent OLT with end-to-end choledocho-choledochostomy. Biliary anastomosis was performed by intermittent suture with T tube placement in 96 cases, without T tube in 39 cases, by continuous suture in posterior wall and intermittent suture in anterior wall and without T tube in 101 cases. Results Thirty-two (13.3%) patients developed BC, with incidences in group 1, 2 and 3 of 17.7%, 15.4% and 7.9%, respectively. The incidence of hepatic hilar and/or intrahepatic bile duct strictures was 8.3%, 2.6% and 1.0%, respectively. BC incidence in group 3 significantly decreased. Twenty patients with biliary stricture underwent endoscopic and/or radiological interventions, and stricture resolution was achieved in 90% of patients with anastomotic strictures and 60% of patients with hepatic hilar and/or intrahepatic strictures. Conclusions Modified biliary tract reconstruction technique contributes to the decrease of BC. Endoscopic and/or radiological interventions should be used for non-ischemic anastomotic biliary strictures or simple hepatic hilar strictures.