Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective To explore the effect of transcription factor E2F7 on the proliferation,migration,invasion,and tumor growth of anaplastic thyroid cancer(ATC)cells in vitro and to elucidate the underlying mechanisms.Methods Lentivirus transfection was used for a stable E2F7 knockdown in CAL-62 cells,and real-time PCR was used to detect E2F7 expression in these cells to verify the trans-fection efficiency.CAL-62 cells were divided into sh-NC and sh-E2F7 groups,and cell proliferation was measured using the CCK-8 assay,whereas cell migration and invasion abilities were measured using the Transwell assay.CAL-62 cells were subcutaneously injected into nude mice to observe tumor growth.The EPD website predicted an E2F7 binding site on the CXCL5 promoter,and the dual-lucif-erase reporter gene assay measured the effect of E2F7 knockdown on the luciferase activity of the CXCL5 promoter.The impact of E2F7 knockdown on CXCL5 levels in CAL-62 cells was assessed through real-time PCR and ELISA.Further,CAL-62 cells were divided into sh-E2F7+vector and sh-E2F7+CXCL5 groups to study the effects of CXCL5 overexpression on cell proliferation,migration,invasion,and the CXCR2/ERK signaling pathway following E2F7 knockdown.Results E2F7 knockdown inhibited CAL-62 cell proliferation,migra-tion,and invasion in vitro and tumor growth in vivo.The CXCL5 promoter has an E2F7 binding site,and E2F7 knockdown reduced the luciferase activity of the CXCL5 promoter.CXCL5 overexpression reversed the inhibitory effect of E2F7 knockdown on cell proliferation,migration,invasion,and the CXCR2/ERK signaling pathway in CAL-62 cells.Conclusion E2F7 promotes ATC cell proliferation,migra-tion,invasion,and tumor growth in vitro by activating the CXCL5/CXCR2/ERK signaling pathway mediated by CXCL5 transcription.

To investigate the existence of tick-borne pathogens infection of rodents at the border of China and the Demo-cratic People's Republic of Korea(DPRK).PCR was used to detect the spotted fever group rickettsiae(SFGR)ompA gene,Ehrlichia chaffeensis(Ec)and Anaplasma phagocytophilum(Ap)16S rRNA,Candidatus Neoehrlichia mikurensis(CNm)groEL gene,Bartonella(Ba)rpoB gene,and Francisella tularensis(Ft)fopA gene in rodents samples collected from Ji'an of Jilin province and Kuandian of Liaoning Province.The positivity rates of 132 wild rats spleen samples,SFGR,Ec,Ap,CNm,Ba,and Ft were 9.85％,12.88％,5.30％,3.79％,51.52％,and 6.06％,respectively,with statistical differences in in-fection rates(x2=149.236,P=0.000).The infection rate of Ba was the highest in wild rats in this area.There was no signifi-cant difference in the infection rate of SFGR,Ec,Ap,CNm,and Ft among different rats species,but there were significant differences in the infection rate of Ba(x2=13.36,P=0.010).The infection rate of Apodemus agrarius was the highest.A-mong 132 wild rats specimens,the coinfection rate of the two pathogens was 15.9％(21/132),with Ba as the main species(15/132),and two cases of coinfection with three pathogens were detected.The infection of six tick-borne pathogens is common in wild rats at the China/DPRK border.Co-infection of two or three pathogens indicates a risk of multiple tick-borne pathogens and mixed natural foci of multiple tick-borne infec-tious diseases.

Investigating the species/biovars,distribution patterns,and genetic correlations of Brucella from sheep in north-west China is critical to reveal the population and epidemiological characteristics of the Brucella melitensis.In this study,con-ventional identification and AMOS-PCR were used to determine the species/biovars of Brucella isolated from 13 regions in northwest China.MLST and MLVA-16 genotyping methods were used to analyze the genetic characteristics of the strains.Con-ventional identification and AMOS-PCR detection revealed that 59 Brucella melitensis were isolated in this study,in-cluding 22 strains from Inner Mongolia,17 strains from Xin-jiang,13 strains from Gansu,and 7 strains from Qinghai,of which 58 strains were B.melitensis biovar 3,and one strain was B.melitensis biovar 1.MLST analysis indicated that 90％(53/59)of B.melitensis were of ST8 sequence type,the dominant epidemic population.The MLVA-11 survey demonstrated that 59 B.melitensis strains clustered into six MLVA-11 genotypes,and 87％of the strains were of MLVA-11 genotype 116.Therefore,the predominant strains in the northwest region were from the Eastern Mediterranean lineage.MLVA-16 divided 59 strains of B.melitensis into 40 gen-otypes,eight of which were shared genotypes.Each genotype was composed of two to seven strains from the same region,thereby indicating that the cases of each shared genotype were outbreaks from a common source of infection.All shared MLVA-16 genotypes comprised strains from the same province,thus indicating apparent regional clustering characteristics of strains in each province.In a genetic comparison between populations and isolated strains from the spleens of sheep,multiple identical MLVA-16 genotypes were found to be composed of strains from different hosts.These findings indicated a transmission path-way from sheep/goats to humans.B.melitensis biovar 3 was the main pathogen causing animal brucellosis in the northwest re-gion,and infected sheep were the main brucellosis infection source in the regional population.The ST8 strains were the domi-nant epidemic population,and the MLVA genotype of strains in each region showed clear regional clustering characteristics.

Objective To explore the effects of the long non-coding RNA(lncRNA)NK2 homeobox 1-antisense RNA 1(NK2-1-AS1),which mediates the microRNA(miR)-96-5p/PR domain-containing protein 16(PRDM16)axis,on anaplastic thyroid cancer(ATC)cell proliferation,migration,and invasion in vitro and transplanted tumor growth in vivo.Methods The differentially expressed lncRNA NKX2-1-AS1 in ATC tissues and cells,its target miRNA miR-96-5p,and its downstream target gene PRDM16 were screened using a bioinformatics analysis.The dual-luciferase reporter assay validated the relationship between NKX2-1-AS1 and miR-96-5p as well as the connection between miR-96-5p and PRDM16.Western blotting was performed to detect the effect of miR-96-5p overexpression on PRDM16 in CAL-62 cells overexpressed with NKX2-1-AS1.Plate clone formation,scratch,and Transwell assays were used to detect the effects of PRDM16knockdown on the proliferation,migration,and invasion of CAL-62 cells overexpressing NKX2-1-AS1.CAL-62 cells were injected subcutaneously into nude mice and the effect was observed of PRDM16knockdown on the growth of transplanted tumors of CAL-62 cells overexpressing NKX2-1-AS1.Results The bioinformatics analysis revealed that the NK2-1-AS1/miR-96-5p/PRDM16 axis was involved in regulating ATC development.The dual-luciferase reporter assay demonstrated that NKX2-1-AS1 bound to miR-96-5p and miR-96-5p bound to PRDM16.NKX2-1-AS1 overexpression upregulated PRDM16 protein expression in CAL-62 cells,while miR-96-5p overexpression reversed this phenomenon.NKX2-1-AS1 overexpression inhibited CAL-62 cellular proliferation,migration,and invasion in vitro and transplanted tumor growth in vivo,while knocking down PRDM16 reversed these phenomena.Conclusion NK2-1-AS1 may compete with miR-96-5p as an endogenous RNA to bind to its downstream target gene,PRDM16,and upregulate its expression,thus inhibiting ATC cell proliferation,migration,and invasion in vitro and transplanted tumor growth in vivo.

Anaplastic thyroid carcinoma(ATC)is the most aggressive malignancy with poor prognosis.The pathogenesis of ATC is complex,and there is no effective treatment at present.In recent years,with the deep understanding of the genetic(such as BRAF V600E,TP53,TERT,PIK3CA mutations,etc.)and epigenetic(such as histone methylation,histone deacetylation,microRNA regulatory pathways,etc.)changes driving ATC,molecular targeted therapy has brought new hope to ATC patients.This article reviews the molecular mechanisms of ATC and the latest achievements in targeted therapy and other therapies.

Objective:To investigate the expression of HBB in anaplastic thyroid cancer(ATC)cells and its regulatory effect on proliferation,invasion,migration and apoptosis of ATC cells and its potential mechanism.Methods:The expression of HBB in thyroid cancer and paracancerous tissues was analyzed through TIMER database.The correlation between the expression of HBB and the overall survival time of thyroid cancer patients was analyzed through KM-plotter database.The expression of HBB mRNA in ATC cells was detected by RT-qPCR.The HBB knockout or overexpression plasmid was transfected into ATC cells.The expression of HBB protein was detected by Western blot.The proliferation activity was detected by CCK-8 assay.The migration and invasion ability was detected by Transwell assay.The apoptosis was detected by flow cytometry.The expression of β-catenin was detected by Western blot.Results:The expression of HBB was low in thyroid cancer,and the overall survival time of patients with high expression of HBB was high.The expression of HBB protein was down-regulated in ATC cells.Knockout of HBB increased the ability of proliferation,migration and invasion of ATC cells and the expression of β-catenin protein,and inhibited apoptosis.However,overexpression of HBB decreased the ability of proliferation,migration and invasion of ATC cells and the expression of β-catenin protein,and promoted apoptosis.Conclusions:High HBB expression is associated with higher overall survival in patients with thyroid cancer.It may inhibit the proliferation,migration and invasion of ATC cells and promote apoptosis through Wnt/β-catenin signal pathway.

Objective To investigate the value of polar residual network(PResNet)model for assisting evaluation on rat myocardial infarction(MI)segment in myocardial contrast echocardiography(MCE).Methods Twenty-five male SD rats were randomly divided into MI group(n=15)and sham operation group(n=10).MI models were established in MI group through ligation of the left anterior descending coronary artery using atraumatic suture,while no intervention was given to those in sham operation group after thoracotomy.MCE images of both basal and papillary muscle levels on the short axis section of left ventricles were acquired after 1 week,which were assessed independently by 2 junior and 2 senior ultrasound physicians.The evaluating efficacy of MI segment,the mean interpretation time and the consistency were compared whether under the assistance of PResNet model or not.Results No significant difference of efficacy of evaluation on MI segment was found for senior physicians with or without assistance of PResNet model(both P＞0.05).Under the assistance of PResNet model,the efficacy of junior physicians for diagnosing MI segment was significantly improved compared with that without the assistance of PResNet model(both P＜0.01),and was comparable to that of senior physicians.Under the assistance of PResNet model,the mean interpretation time of each physician was significantly shorter than that without assistance(all P＜0.001),and the consistency between junior physicians and among junior and senior physicians were both moderate(Kappa=0.692,0.542),which became better under the assistance(Kappa=0.763,0.749).Conclusion PResNet could improve the efficacy of junior physicians for evaluation on rat MI segment in MCE images,shorten interpretation time with different aptitudes,also improve the consistency to some extent.