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 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.

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 efficacy and safety of injectable modified sodium hyaluronate gel DX23 in filling and treating midface depression.Methods:A prospective, randomized, multicenter, "no treatment" controlled study was conducted. Patients with midface depression who were treated from March 2019 to February 2021 at Beijing Anzhen Hospital Affiliated to Capital Medical University, Qilu Hospital of Shandong University, and Jining First People’s Hospital were enrolled. Patients were randomized using a stratified block randomization method with a random function list. The experimental group received injectable modified sodium hyaluronate gel DX23 to treat midface depression. The concentration of sodium hyaluronate in DX23 was 23 mg/ml. The syringe was inserted perpendicularly to the skin at a 90-degree angle, and the injection layers were the superficial periosteum or the subcutaneous layer. The injection volume ranged from 1 to 6 ml. The control group received no treatment. The upper boundary of the midface extended outward from the zygomatic arch to the upper margin of the helix and inward to the line connecting the outer canthus. The lower boundary was the line connecting the corner of the mouth to the earlobe. Researchers used the midface aesthetic scales (MAS) response rate at 6 months post-injection as the primary indicator to evaluate the efficacy in improving the severity of midface depression. A reduction of 1 point in the MAS score compared to pre-treatment was considered a response, i. e., effective. Secondary indicators included the MAS response rates at 6 and 12 months after the last treatment (MAS response rate=number of MAS responders/total cases × 100%), the average change in three-dimensional midface volume images, the global aesthetic improvement scale (GAIS) response rate, patient satisfaction regarding the degree of improvement in midface volume, and monitoring of adverse reactions. Data analysis was performed using SPSS 25.0, SAS 9.04, and StataIC 15.0 software. The full analysis set (FAS) and the per-protocol set (PPS) were selected for analysis. Inferential analysis used t-tests and chi-square tests, with P<0.05 considered statistically significant. Results:A total of 164 patients were enrolled. The experimental group included 134 patients (7 males and 127 females) with an average age of 43.0±9.7 years (ranging from 21.6 to 66.6 years). The control group included 30 patients (5 males and 25 females) with an average age of 39.3±11.1 years (ranging from 25.6 to 43.5 years). The experimental group received bilateral midface depression filling, with an initial use of injectable modified sodium hyaluronate gel DX23 at a volume of (4.07±1.28) ml. In the experimental group, 3 cases were lost to follow-up at 30 days, 2 cases at 60 days, and 10 cases were excluded due to protocol violations. Fifteen patients entered FAS but not PPS. Ultimately, 119 patients completed the trial. The MAS response rates in the experimental group at 6 and 12 months post-treatment were 94.96% (113/119) and 56.30% (67/119), respectively. The control group’s MAS response rate at 6 months was 3.33% (1/30). At the 6-month follow-up post-treatment, the GAIS response rates evaluated by researchers and patients in the experimental group were 97.48% (116/119) (PPS) and 97.69% (27/30) (FAS), respectively. In the control group, the GAIS response rate evaluated by researchers was 3.33% (1/30) (FAS, PPS), and the patient GAIS response rate was 0% (0/30) (FAS, PPS). There were statistically significant differences between the two groups in both researcher and patient GAIS response rates (both P<0.01). At 6 months post-injection, comparisons of midface volume changes from baseline between the experimental and control groups showed statistically significant differences [(1.65±1.40) ml (PPS) vs. (0.12±0.85) ml; (1.55±1.44) ml (FAS) vs. (0.12±0.85) ml; both P<0.001]. At the 6-month follow-up in the experimental group, 1 case was lost to follow-up. In the PPS, 81 patients were "satisfied, " 34 were "very satisfied, " and 3 were "neutral." In the control group, 29 patients were "neutral, " and 1 was "dissatisfied." A total of 128 patients in the experimental group experienced injection site reactions, including swelling, hardness, tenderness, pain, lumps (protrusions), and bruising. Over 75% of patients resolved spontaneously within 8 days. Three cases received hot compress treatment and resolved within 28 days. One case experienced swelling of the left lower eyelid 1 day after injection, which resolved after local compression for 3 months. In the control group, 1 case developed circulatory ischemia and carotid atherosclerosis 12 months after the trial began. Conclusion:Injectable modified sodium hyaluronate gel DX23 corrects midface depression through local volume augmentation and is characterized by safety and durability.

Objective:To investigate the efficacy and safety of injectable modified sodium hyaluronate gel DX23 in filling and treating midface depression.Methods:A prospective, randomized, multicenter, "no treatment" controlled study was conducted. Patients with midface depression who were treated from March 2019 to February 2021 at Beijing Anzhen Hospital Affiliated to Capital Medical University, Qilu Hospital of Shandong University, and Jining First People’s Hospital were enrolled. Patients were randomized using a stratified block randomization method with a random function list. The experimental group received injectable modified sodium hyaluronate gel DX23 to treat midface depression. The concentration of sodium hyaluronate in DX23 was 23 mg/ml. The syringe was inserted perpendicularly to the skin at a 90-degree angle, and the injection layers were the superficial periosteum or the subcutaneous layer. The injection volume ranged from 1 to 6 ml. The control group received no treatment. The upper boundary of the midface extended outward from the zygomatic arch to the upper margin of the helix and inward to the line connecting the outer canthus. The lower boundary was the line connecting the corner of the mouth to the earlobe. Researchers used the midface aesthetic scales (MAS) response rate at 6 months post-injection as the primary indicator to evaluate the efficacy in improving the severity of midface depression. A reduction of 1 point in the MAS score compared to pre-treatment was considered a response, i. e., effective. Secondary indicators included the MAS response rates at 6 and 12 months after the last treatment (MAS response rate=number of MAS responders/total cases × 100%), the average change in three-dimensional midface volume images, the global aesthetic improvement scale (GAIS) response rate, patient satisfaction regarding the degree of improvement in midface volume, and monitoring of adverse reactions. Data analysis was performed using SPSS 25.0, SAS 9.04, and StataIC 15.0 software. The full analysis set (FAS) and the per-protocol set (PPS) were selected for analysis. Inferential analysis used t-tests and chi-square tests, with P<0.05 considered statistically significant. Results:A total of 164 patients were enrolled. The experimental group included 134 patients (7 males and 127 females) with an average age of 43.0±9.7 years (ranging from 21.6 to 66.6 years). The control group included 30 patients (5 males and 25 females) with an average age of 39.3±11.1 years (ranging from 25.6 to 43.5 years). The experimental group received bilateral midface depression filling, with an initial use of injectable modified sodium hyaluronate gel DX23 at a volume of (4.07±1.28) ml. In the experimental group, 3 cases were lost to follow-up at 30 days, 2 cases at 60 days, and 10 cases were excluded due to protocol violations. Fifteen patients entered FAS but not PPS. Ultimately, 119 patients completed the trial. The MAS response rates in the experimental group at 6 and 12 months post-treatment were 94.96% (113/119) and 56.30% (67/119), respectively. The control group’s MAS response rate at 6 months was 3.33% (1/30). At the 6-month follow-up post-treatment, the GAIS response rates evaluated by researchers and patients in the experimental group were 97.48% (116/119) (PPS) and 97.69% (27/30) (FAS), respectively. In the control group, the GAIS response rate evaluated by researchers was 3.33% (1/30) (FAS, PPS), and the patient GAIS response rate was 0% (0/30) (FAS, PPS). There were statistically significant differences between the two groups in both researcher and patient GAIS response rates (both P<0.01). At 6 months post-injection, comparisons of midface volume changes from baseline between the experimental and control groups showed statistically significant differences [(1.65±1.40) ml (PPS) vs. (0.12±0.85) ml; (1.55±1.44) ml (FAS) vs. (0.12±0.85) ml; both P<0.001]. At the 6-month follow-up in the experimental group, 1 case was lost to follow-up. In the PPS, 81 patients were "satisfied, " 34 were "very satisfied, " and 3 were "neutral." In the control group, 29 patients were "neutral, " and 1 was "dissatisfied." A total of 128 patients in the experimental group experienced injection site reactions, including swelling, hardness, tenderness, pain, lumps (protrusions), and bruising. Over 75% of patients resolved spontaneously within 8 days. Three cases received hot compress treatment and resolved within 28 days. One case experienced swelling of the left lower eyelid 1 day after injection, which resolved after local compression for 3 months. In the control group, 1 case developed circulatory ischemia and carotid atherosclerosis 12 months after the trial began. Conclusion:Injectable modified sodium hyaluronate gel DX23 corrects midface depression through local volume augmentation and is characterized by safety and durability.

Tacrolimus (TAC), also called FK506, is one of the classical immunosuppressants to prevent allograft rejection after liver transplantation. However, it has been proved to be associated with post-transplant hyperlipemia. The mechanism behind this is unknown, and it is urgent to explore preventive strategies for hyperlipemia after transplantation. Therefore, we established a hyperlipemia mouse model to investigate the mechanism, by injecting TAC intraperitoneally for eight weeks. After TAC treatment, the mice developed hyperlipemia (manifested as elevated triglyceride (TG) and low-density lipoprotein cholesterol (LDL-c), as well as decreased high-density lipoprotein cholesterol (HDL-c)). Accumulation of lipid droplets was observed in the liver. In addition to lipid accumulation, TAC induced inhibition of the autophagy-lysosome pathway (microtubule-associated protein 1 light chain 3β (LC3B) II/I and LC3B II/actin ratios, transcription factor EB (TFEB), protein 62 (P62), and lysosomal-associated membrane protein 1 (LAMP1)) and downregulation of fibroblast growth factor 21 (FGF21) in vivo. Overexpression of FGF21 may reverse TAC-induced TG accumulation. In this mouse model, the recombinant FGF21 protein ameliorated hepatic lipid accumulation and hyperlipemia through repair of the autophagy-lysosome pathway. We conclude that TAC downregulates FGF21 and thus exacerbates lipid accumulation by impairing the autophagy-lysosome pathway. Recombinant FGF21 protein treatment could therefore reverse TAC-caused lipid accumulation and hypertriglyceridemia by enhancing autophagy.
Animals ; Mice ; Tacrolimus ; Liver ; Cholesterol, LDL ; Autophagy ; Disease Models, Animal

Atrial fibrillation (AF) is one of the most common clinical arrhythmias. As the population ages, there is an upward trend in its prevalence. The risk factors associated with increased risk of AF include old age, diabetes, hypertension, and cancer. Studies have shown that in all age groups, the risk of death, hospitalization expenses, and hospitalization time of cancer patients with AF were higher than that without AF. Thus, increased systemic inflammation, electrolyte abnormalities, and neurohormonal changes in patients with prostate cancer (PCa) lead to a significantly higher incidence of AF than other cancers. However, the treatment of prostate cancer, including surgery, chemotherapy and radiotherapy, may also increase the risk of AF. In this review, relevant literatures are collected to understand the mechanism of AF in patients with PCa, determine the relationship between PCa and AF and its effect on hospitalized prognosis, and provide strategies for the prevention and treatment of AF in patients with PCa.