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 investigate the effect of propofol on bone metabolism in glucocorticoid induced osteoporo-sis(GIOP)in rat models by regulating the PI3K/AKT/mTOR signaling pathway.Methods Rats were grouped into a blank group,model(GIOP)group,2.5 mg/kg and 5 mg/kg propofol groups and a propofol+LY294002(5 mg/kg propofol+5 mg/kg LY294002)group,with 12 rats in each group.A small animal bone densitometer was used to measure the tibial bone density(BMD)of rats.ELISA was applied to detect the level of bone gla-protein(BGP),procollagen Ⅰ N-terminal propeptide(PINP)and type Ⅰ collagen cross-linked C-terminal peptide(CTX-Ⅰ)in rat serum.HE staining microscopy was applied to observe the pathological morphology of rat bone tis-sue.RT-qPCR was used to detect the mRNA expression of Pi3k,Akt,mTor,Beclin-1,and p62 in bone tissue.Western blot was used to detect the expression level of PI3K/AKT/mTOR signaling pathway related proteins and autophagy related proteins in rat bone tissue.Results Compared with the blank group,the tibial BMD,serum BGP,and CTX-Ⅰ levels of GIOP group decreased(P＜0.05).mRNA expression of Pi3k,Akt,mTor and Beclin-1 in bone tissue decreased(P＜0.05).mRNA and protein expression of p62 increased(P＜0.05).The expression of PI3K/AKT/mTOR signaling pathway related proteins and Beclin-1 protein in bone tissue decreased(P＜0.05).Compared to GIOP group,the changes of above indicators were obviously alleviated in the 2.5 mg/kg and 5 mg/kg propofol groups(P＜0.05).On the basis of treatment with 5 mg/kg propofol,the use of LY294002 inhibited activation of the PI3K/AKT/mTOR signaling pathway and autophagy and interfered with the positive regulatory effects of propofol on bone me-tabolism and bone tissue morphology improvement in GIOP rats(P＜0.05).Conclusions Propofol may improve bone metabolism in rat models of GIOP through potential mechanism of activating PI3K/AKT/mTOR signaling pathway.

Objective:To investigate the predictive role of relative diffusion-weighted imaging (DWI) signal intensity (DWI-rSI) in outcome in patients with anterior circulation large vessel occlusion cardioembolic stroke and successful recanalization after endovascular therapy (EVT).Methods:Patients with anterior circulation large vessel occlusion stroke due to cardioembolic embolism underwent EVT and successful recanalization at the Affiliated Hospital of Yangzhou University from March 2017 to March 2023 were retrospectively included. According to the modified Rankin Scale score 3 months after procedure, the patients were divided into a good outcome group (0-2 points) and a poor outcome group (3-6 points). Multivariate logistic regression analysis was used to identify independent predictive factors for poor outcome. Results:A total of 59 patients were enrolled, including 29 males (49.2%), median age of 74 years (interquartile range, 68-80 years). The median baseline National Institutes of Health Stroke Scale (NIHSS) score was 15 (12-21), and the median DWI Alberta Stroke Program Early CT Score (ASPECTS) was 8 (5-9). Thirty-two patients (54.2%) had good outcome, and 27 (45.8%) had poor outcome. Among them, 9 patients (15.3%) died (6 died from cerebral herniation after malignant brain edema, 2 died from complications, and 1 died from severe intracranial hemorrhage after procedure). Twenty-one patients (35.6%) experienced hemorrhagic transformation, including 12 (20.3%) with symptomatic intracranial hemorrhage. There were significant differences in baseline systolic blood pressure, NIHSS score, DWI-ASPECTS, DWI-rSI, and incidence of symptomatic intracranial hemorrhage between the good outcome group and the poor outcome group (all P<0.05). Multivariate logistic regression analysis showed that baseline systolic blood pressure (odds ratio 0.977, 95% confidence interval 0.919-0.991; P=0.015) and DWI-rSI (odds ratio 11.809, 95% confidence interval 1.932-72.170; P=0.008) were the independent predictors for poor outcome. Conclusion:DWI-rSI can predict the outcome of patients with anterior circulation large vessel occlusion cardioembolic stroke and successful recanalization after EVT.

Objective:To investigate the effect of regional leptomeningeal collateral circulation (rLMC) score based on CT angiography (CTA) and onset-to-reperfusion time (OTR) on the outcome after endovascular treatment (EVT) in patients with anterior circulation acute large vessel occlusive stroke (ACA-LVOS).Methods:Patients with ACA-LVOS underwent EVT in the Department of Neurology, the Affiliated Hospital of Yangzhou University from July 2017 to July 2023 were included retrospectively. The rLMC score 0-10 was defined as poor collateral circulation, and 11-20 were defined as good collateral circulation. At 90 days after EVT, the modified Rankin Scale (mRS) was used to evaluate the outcome. A score of 0-2 was defined as a good outcome and 3-6 were defined as a poor outcome. Multivariate logistic regression analysis was used to determine the independent influencing factors of the outcome after EVT. Results:A total of 144 patients with ACA-LVOS underwent EVT were enrolled, including 78 males (54.2%), median aged 73 years. The median baseline National Institutes of Health Stroke Scale (NIHSS) score was 16, the median baseline Alberta Stroke Program Early CT Score (ASPECTS) was 9, and the median OTR was 330.5 minutes. Eighty patients (55.6%) had good collateral circulation, 63 (43.8%) had poor outcome, including 13 deaths. Univariate analysis showed that there were significant differences in hypertension, previous stroke history, smoking, triglycerides, baseline NIHSS score, baseline ASPECTS, OTR, and collateral circulation status between the good outcome group and the poor outcome group (all P<0.05). Multivariate logistic regression analysis showed that good collateral circulation (odds ratio [ OR] 0.223, 95% confidence interval [ CI] 0.077-0.643; P=0.005) was an independent predictor of good outcome. In the poor collateral circulation group, longer OTR was an independent predictor of poor outcome ( OR 1.020, 95% CI 1.008-1.032; P=0.001). In the good collateral circulation group, longer OTR was not an independent risk factor for poor outcome ( OR 1.005, 95% CI 1.000-1.010; P=0.062). Conclusion:rLMC score based on CTA and OTR are the independent predictors of the outcome after EVT in patients with ACA-LVOS.

Background and Aims:Cholangiocarcinoma,a rare malignant tumor,is difficult to diagnose and often detected at an advanced stage,limiting treatment options to palliative care.Conventional chemotherapy drugs have poor efficacy against cholangiocarcinoma,making the search for new treatments critical.This study was conducted to investigate the effects of Huai'erjunzhi on the malignant biological behavior of human cholangiocarcinoma cells and its relationship with the TGF-β/Smad pathway,aiming to provide a theoretical basis for the use of Huai'erjunzhi in cholangiocarcinoma treatment. Methods:Human normal liver cells(L-02)and human cholangiocarcinoma cells(HuCCT1)were incubated with different concentrations of Huai'erjunzhi for various durations.Cell proliferation was assessed,and the half-maximal inhibitory concentration(IC50)was calculated.HuCCT1 cells were divided into a negative control group(no intervention),a positive control group(15 mg/L cisplatin),and different Huai'erjunzhi intervention groups(1/5 IC50,2/5 IC50,and IC50 based on preliminary experimental results).Scratch and Transwell assays were used to measure cell migration and invasion,while Western blot was employed to detect the expression of proteins related to the TGF-β/Smad pathway in HuCCT1 cells. Results:Only high concentrations of Huai'erjunzhi(＞312.5 mg/L)significantly inhibited the proliferation of L-02 cells.Huai'erjunzhi significantly inhibited the proliferation of HuCCT1 cells at concentrations above 5 mg/L in a concentration-dependent manner(all P＜0.05),with IC50 values of 138.52 mg/L at 24 h,99.41 mg/L at 48 h,and 113.52 mg/L at 72 h.Compared with the negative control group,the positive control group and the three Huai'erjunzhi intervention groups(20,40,and 100 mg/L)exhibited reduced migration distance,decreased invasive cell numbers,lower expression of TGF-β1,Smad2,Smad3,Smad4,N-cadherin,Snail,and Slug,and increased expression of E-cadherin(all P＜0.05).Compared with the positive control group,these changes in the Huai'erjunzhi groups were less pronounced but showed a clear concentration-dependent relationship(all P＜0.05). Conclusion:Huai'erjunzhi can potentially inhibit the malignant biological behavior of HuCCT1 cells by inhibiting the TGF-β/Smad pathway.

Objective To investigate the effects of dexmedetomidine(Dex)on osteoporosis(OP)rats and possible mechanisms.Methods The rats were divided into sham operation group,osteoporosis model group(OP,replica-ting the OP rat model with bilateral ovariectomies),Dex-L,M,and H(Dex low,medium,and high dose treat-ments)groups and Dex-H+XAV-939 group(Wnt/β-catenin pathway inhibitor).Micro-CT was applied to meas-ure bone mineral density(BMD)and bone microstructure of rat femurs.The three-point bending experiment was applied to analyze the biomechanics of the femur(maximum load,fracture deflection,elastic modulus).HE stai-ning was applied to observe pathological changes in the femur of rats.ELISA method was applied to evaluate bone metabolism indicators such as alkaline phosphatase(ALP),typeⅠ procollagen amino-terminal peptide(PINP)and typeⅠcollagen cross-linked C-telopeptide(CTX-Ⅰ).The expression of Runx2 and Wnt3a was examined by Immunohistochemistry.Western blot was applied to detect the protein expression of Runx2 and Wnt3a/β-catenin pathway in femoral tissue.Results Compared to the Sham group,the bone volume and number of trabeculae in OP group were obviously reduced,the maximum load,fracture deflection,elastic modulus,BMD,Tb.Th,Tb.N,BV/TV,ALP,PINP,Runx2,Wnt3a,β-catenin expression decreased,CTX-Ⅰ increased(P＜0.05).Compared to the OP group,the bone trabecular structure in the Dex-L,M,and H groups was restored,the maxi-mum load,fracture deflection,elastic modulus,BMD,Tb.Th,Tb.N,BV/TV,ALP,PINP,Runx2,Wnt3a,β-catenin expression all increased but CTX-Ⅰ decreased(P＜0.05).Compared to the Dex-H group,the bone trabecular injury in the Dex-H+XAV-939 group showed a more severe damage.The maximum load,fracture de-flection,elastic modulus,BMD,Tb.Th,Tb.N,BV/TV,ALP,PINP,Runx2,Wnt3a,β-catenin expression decreased while CTX-Ⅰ increased(P＜0.05).Conclusions Dex may antagonize OP effects by improving bone density,biomechanical properties and microstructure.The underlying mechanism might be related to the activation of the Wnt/β-catenin signaling pathway.

Objective:To compare the effect of middle meningeal artery embolization (MMAE) versus conventional therapy for chronic subdural hematoma (CSDH).Methods:Retrospective analysis of 38 patients with 48 CSDHs treated with MMAE from May 2019 to May 2021 was performed. Comparisons were made with a conventional treatment for 126 patients with 126 CSDHs from January 2016 to May 2021. The MMAE and conventional treatment patients were matched by the propensity score matching method, and a total of 25 pairs of patients (31 pairs of CSDHs) were successfully matched. The CSDH recurrence, rescue treatment, radiographic follow-up outcome, clinical improvement and complication between the two groups were compared by t test, χ 2 test or Fisher exact probability methods. Results:The rescue treatment rate in MMAE group was significantly lower than that in conventional treatment group [0 (0/31) vs 19.4% (6/31), P=0.024] and the complete resolution rate at 6 months follow-up in MMAE group was significantly higher than that in conventional treatment group [96.8 (30/31) vs 74.2% (23/31), P=0.026]. In terms of CSDH recurrence, there was a trend of lower recurrence in the MMAE group [3.2%(1/31) vs 22.6% (7/31), P=0.053]. The complete resolution rate at 3 months follow-up was 61.3% (19/31) in MMAE group and 45.2% (14/31) in conventional treatment, clinical improvement rate was 92.0% (23/25) in MMAE group and 88.0% (22/23) in conventional treatment, good outcome rate (mRS≤2) was 92.0% (23/25) in MMAE group and 84.0% (21/25) in conventional treatment, complication rate was 0(0/25) in MMAE group and 4.0% (1/25) in conventional treatment, and there were no significant differences in all above-mentioned parameters ( P>0.05). Conclusions:The MMAE may be considered as a safe and effective treatment for CSDH, and MMAE for CSDH is associated with lower trend of recurrence, lower rescue treatment rate and better radiographic follow-up outcome than conventional therapy.

Objective: To construct and identify an overexpression recombinant adenovirus vector carrying the mouse PTG gene(NM＿016854), and to lay a foundation for in-depth study of the function of PTG. Methods: The coding sequence of the mouse PTG gene was chemically synthesized, amplified by polymerase chain reaction(PCR), digested with restriction enzymes, and inserted into the GV314 vector(CMV-MCS-3 FLAG-SV40-EGFP) to obtain the recombinant shuttle plasmid pGV314-PTG. BamHⅠ/AgeⅠ double enzyme digestion was further carried out, and the product was transferred into linearized expression vector pDC315 to construct recombinant adenovirus Ad-PTG, which was transfected into HEK293 T cells and packaged into recombinant virus particles. After repeated amplification of several generations of HEK293 T cells, the recombinant adenovirus was purified and titer detected. Finally, PCR, Western blot and sequencing were used to verify the recombinant adenovirus. Results: After PCR, Western blot and sequencing, the results showed that the pGV314-CMV-MCS-3 FLAG-SV40-EGFP-PTG overexpression adenovirus vector(Ad-PTG) was successfully constructed, and the virus titer measured by end-point dilution method was 4×1010PFU/ml, Western blot and RT-qPCR showed that the protein and mRNA expression levels of PTG increased significantly. Conclusion The recombinant adenovirus vector carrying mouse PTG gene is successfully constructed, and the expression of PTG gene in hepatocytes is effectively up regulated.