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 examine the impact of moderate-intensity intermittent aerobic training on the expression of microRNA-21-3p(miR-21-3p),so as to establish a theoretical foundation for under-standing the potential mechanisms of exercise interventions mitigating the decline in learning and memo-ry functions associated with brain aging. Methods Forty-five three-month specific pathogen-free(SPF) male Sprague-Dawley(SD) rats were randomly divided into a control group(group C),an aging group (group A),and an aging+exercise group(group AE),following a one-week acclimatization period. Group A and AE were administered intraperitoneal injections of D-galactose(D-gal) for six weeks,and the latter group underwent an eight-week regimen of moderate-intensity interval aerobic training. Behavioral assessments were conducted in all groups 24 hours after modeling. Nissl staining was used to detect the distribution of neurons,while in situ terminal transferase labeling(TUNEL) was employed to identify apoptosis in hippocampal cells. Moreover,small RNA sequencing was conducted to detect miRNA expression,while real-time quantitative polymerase chain reaction(qRT-PCR) was employed to measure the relative content of miR-21-3p. Meanwhile,the targeting relationship between miR-21-3p and tumor protein p53(p53) was confirmed using the dual luciferase reporter gene assay,while the ex-pression levels of p53,the B lymphoblastoma-2 protein family member X(Bax),and the B lympho-blastoma-2(Bcl-2) were measured using Western Blotting. Results ①The results of the Morris water maze positioning navigation experiment before and after the intervention showed that the overall swim-ming distance of rats in groups A and AE was significantly longer than group C(P<0.05,P<0.01),with that of group AE significantly shorter than group A(P<0.01,P<0.05). ② Nissl's staining re-vealed that,compared to group C,hippocampal neurons in group A exhibited disorganization,reduced staining intensity,indistinct nuclei from surrounding tissues,and a scarcity of Nissl bodies,while those of group AE were sparse,with fewer levels and significantly reduced numbers. However,com-pared with group A,the hippocampal neurons in group AE were arranged more neatly,with more lay-ers and more Nissl bodies. ③TUNEL results showed that the apoptosis rate of hippocampal cells in group A and AE was significantly higher than group C(P<0.01,P<0.05),with that of group AE signif-icantly lower than group A(P<0.01). ④ Small RNA sequencing results showed that the expression of plasma exosomes miR-21-3p in group A and AE was significantly higher than group C(P<0.01,P<0.05),with that of group AE significantly lower than group A(P<0.01). ⑤According to the results of qRT-PCR,the expression of miR-21-3p in group A and AE was significantly higher than group C(P<0.01),with that of group AE significantly lower than group A(P<0.05). ⑥Luciferase experiment showed that miR-21-3p had a targeted relationship with p53. Compared with Vector mimics+pcD-NA3.1-p53,miR-21-3p mimics and pcDNA3.1-p53 co-transfected HEK293T cells could significantly improve p53 luciferase activity. ⑦According to Western Blotting results,the protein expressions of p53 and Bax and the ratio of Bax/Bcl2 in group A and AE were significantly higher than group C(P<0.01,P<0.05),but that of Bcl-2 was significantly lower than the latter group(P<0.01). Moreover,the expression of p53 and Bax protein and the ratio of Bax/Bcl-2 in group AE were significantly low-er than group A(P<0.05,P<0.01),but that of Bcl-2 protein was significantly higher than group A(P<0.01). Conclusions It is suggested that 8-week moderate intensity intermittent aerobic training may down-regulate miR-21-3p mediated by peripheral blood exosomes,reduce the expression of miR-21-3p in brain tissue,target miR-21-3p to bind p53,and reduce the occurrence of apoptosis,thus im-proving the learning and memory ability of rats.

Objective To examine the impact of moderate-intensity intermittent aerobic training on the expression of microRNA-21-3p(miR-21-3p),so as to establish a theoretical foundation for under-standing the potential mechanisms of exercise interventions mitigating the decline in learning and memo-ry functions associated with brain aging. Methods Forty-five three-month specific pathogen-free(SPF) male Sprague-Dawley(SD) rats were randomly divided into a control group(group C),an aging group (group A),and an aging+exercise group(group AE),following a one-week acclimatization period. Group A and AE were administered intraperitoneal injections of D-galactose(D-gal) for six weeks,and the latter group underwent an eight-week regimen of moderate-intensity interval aerobic training. Behavioral assessments were conducted in all groups 24 hours after modeling. Nissl staining was used to detect the distribution of neurons,while in situ terminal transferase labeling(TUNEL) was employed to identify apoptosis in hippocampal cells. Moreover,small RNA sequencing was conducted to detect miRNA expression,while real-time quantitative polymerase chain reaction(qRT-PCR) was employed to measure the relative content of miR-21-3p. Meanwhile,the targeting relationship between miR-21-3p and tumor protein p53(p53) was confirmed using the dual luciferase reporter gene assay,while the ex-pression levels of p53,the B lymphoblastoma-2 protein family member X(Bax),and the B lympho-blastoma-2(Bcl-2) were measured using Western Blotting. Results ①The results of the Morris water maze positioning navigation experiment before and after the intervention showed that the overall swim-ming distance of rats in groups A and AE was significantly longer than group C(P<0.05,P<0.01),with that of group AE significantly shorter than group A(P<0.01,P<0.05). ② Nissl's staining re-vealed that,compared to group C,hippocampal neurons in group A exhibited disorganization,reduced staining intensity,indistinct nuclei from surrounding tissues,and a scarcity of Nissl bodies,while those of group AE were sparse,with fewer levels and significantly reduced numbers. However,com-pared with group A,the hippocampal neurons in group AE were arranged more neatly,with more lay-ers and more Nissl bodies. ③TUNEL results showed that the apoptosis rate of hippocampal cells in group A and AE was significantly higher than group C(P<0.01,P<0.05),with that of group AE signif-icantly lower than group A(P<0.01). ④ Small RNA sequencing results showed that the expression of plasma exosomes miR-21-3p in group A and AE was significantly higher than group C(P<0.01,P<0.05),with that of group AE significantly lower than group A(P<0.01). ⑤According to the results of qRT-PCR,the expression of miR-21-3p in group A and AE was significantly higher than group C(P<0.01),with that of group AE significantly lower than group A(P<0.05). ⑥Luciferase experiment showed that miR-21-3p had a targeted relationship with p53. Compared with Vector mimics+pcD-NA3.1-p53,miR-21-3p mimics and pcDNA3.1-p53 co-transfected HEK293T cells could significantly improve p53 luciferase activity. ⑦According to Western Blotting results,the protein expressions of p53 and Bax and the ratio of Bax/Bcl2 in group A and AE were significantly higher than group C(P<0.01,P<0.05),but that of Bcl-2 was significantly lower than the latter group(P<0.01). Moreover,the expression of p53 and Bax protein and the ratio of Bax/Bcl-2 in group AE were significantly low-er than group A(P<0.05,P<0.01),but that of Bcl-2 protein was significantly higher than group A(P<0.01). Conclusions It is suggested that 8-week moderate intensity intermittent aerobic training may down-regulate miR-21-3p mediated by peripheral blood exosomes,reduce the expression of miR-21-3p in brain tissue,target miR-21-3p to bind p53,and reduce the occurrence of apoptosis,thus im-proving the learning and memory ability of rats.

Objective We studied the EHD2 expression level in NSCLC and its association with clinicopathological features and prognosis.Methods The EHD2 expression level in NSCLC was measured by Western blot in 4 pairs fresh tissues and immunohistochemistry on 91 parffin-embedded slices.These experiments were used to explore the relationship of EHD2 and Ki-67 in the clinical parameters,as well as the relationship with EHD2 and prognosis.Results Western blot showed EHD2 expression level was low in 4 pairs NSCLC tissues.The results by immunohistochemistry showed that the expression of EHD2 was higher in well-differentiated NSCLC tissues than that in poor-differentiated tissues,which was opposite to the Ki-67 expression.Statistical methods revealed that EHD2 protein in NSCLC was significantly correlated with histological grade,pTNM staging,tumor size,lymph node metastasis as well as Ki-67.Low EHD2 expression was correlated with poor prognosis.Conclusions The abnormal expression of EHD2 might be closely related to the initiation and progress of NSCLC.EHD2 might be an indicator of the prognosis of NSCLC,which could be a potential target for NSCLC therapy.