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.

Adolescent idiopathic scoliosis(AIS)is a complex three-dimensional deformity involving coronal,sagittal,and axial planes,with a prevalence that should not be overlooked.With advancements in technology and in-depth research,an increasing number of hospitals and physicians are exploring standardized diagnostic and treatment approaches for AIS.Comprehensive and in-depth understanding is required for AIS,including its etiology,screening and diagnosis,classification,assessment and examination,treatment options,exploration of current focus,and evaluation of quality of life.Such understanding ensures that the diagnostic and treatment are scientific,standardized,and timely.Based on the principles of evidence-based medicine,a consensus on the diagnosis and treatment of AIS is reached after multiple discussions among spinal surgery experts,aiming to provide reference and guidance for clinical practice.

Objective To investigate the value of integrin subunit αM(ITGAM)and integrin subunit β2(ITGB2)levels in peripheral blood mononuclear cells(PBMC)in the diagnosis and prognosis evaluation for patients with severe acute pancreatitis(SAP)complicated with acute lung injury(ALI).Methods A total of 205 patients with SAP admitted from November 2022 to February 2024 in the hospital were selected,and they were divided into ALI group(103 cases)and non-ALI group(102 cases)according to whether they were com-plicated with ALI.Meanwhile,110 healthy people who underwent the physical examination were selected as the control group.The differences of the levels of ITGAM and ITGB2 in PBMC in different groups were com-pared.Logistic regression was used to analyze the influencing factors for ALI in patients with SAP.The re-ceiver operating characteristic(ROC)curve was used to analyze the diagnostic value of levels of ITGAM and ITGB2 in PBMC for SAP patients complicated with ALI and the predictive value for poor prognosis.Results The levels of ITGAM,ITGB2 in PBMC,and serum amylase and urine amylase levels in ALI group were higher than those in non-ALI group and control group(P＜0.05).Multivariate Logistic regression anal-ysis showed that the increase of ITGAM,ITGB2 and serum amylase levels were risk factors for ALI in pa-tients with SAP(P＜0.05).ROC curve results showed that the area under the curve(AUC)of ITGAM com-bined with ITGB2 in diagnosing ALI in patients with SAP was significantly higher than those of ITGAM and ITGB2 alone(P＜0.05).The levels of ITGAM and ITGB2 in PBMC in the poor prognosis group were higher than those in the good prognosis group(P＜0.05).ROC curve results showed that the AUC of ITGAM com-bined with ITGB2 in predicting poor prognosis in patients with SAP complicated with ALI was significantly higher than those of ITGAM and ITGB2 alone(P＜0.05).Conclusion Increased levels of ITGAM and IT-GB2 in PBMC are risk factors for ALI in patients with SAP.ITGAM combined with ITGB2 has a good predic-tive efficacy for the poor prognosis in patients with SAP complicated with ALI,which has important value in clinical practice and is expected to become potential biomarkers.

Objective To investigate the protective effects of paeonol(PAE)on autophagy in human neuroblastoma cells(SH-SY5Y)induced by overexpression of α-synuclein(α-Syn),and to explore its related mechanism.Methods SH-SY5Y cells served as control group,while those induced with A53T-α-Syn mutation were used as model group.Additional groups included PAE(150 μg/ml)group,3-MA(1 mmol/L)group,and PAE(150 μg/ml)+3-MA(1 mmol/L)group.Cell viability was assessed using CCK-8 method,cell morphology was observed under an optical microscope,and protein expressions of α-Syn,LC3-Ⅱ,p62,Beclin-1,phosphorylated c-Jun N-terminal kinase(p-JNK),and p-Bcl-2 were determined by Western blotting.Results Compared with control group,model control exhibited decreased cell survival(P＜0.01),increased α-Syn expression(P＜0.001),reduced expression of autophagy-related proteins LC3-Ⅱ and Beclin-1(P＜0.01,P＜0.05),elevated autophagy substrate protein p62(P＜0.05),and decreased expression of autophagy pathway-related proteins p-JNK and Bcl-2(P＜0.05,P＜0.01).Compared with model group,PAE group showed increased cell survival(P＜0.01),decreased α-Syn and p62 protein expression(P＜0.01,P＜0.05),and increased expression of LC3-Ⅱ,Beclin-1,p-JNK and Bcl-2(P＜0.05).Compared with PAE group,3-MA+PAE group demonstrated increased α-Syn expression(P＜0.05).Conclusions PAE could attenuate the injury of SH-SY5Y cells induced by A53T-α-Syn and eliminate over-expressed α-Syn by activating autophagy pathway,which may be associated with the upregulation of JNK/Bcl-2 mediated autophagy pathway.

Objective:To investigate the mechanism of extract of ginkgo biloba (EGB) on mitochondrial autophagy in breast cancer cells MCF-7.Methods:Breast cancer MCF-7 cells were divided into four groups. EGB with mass concentrations of 40, 80, 120 mg/L was used to incubate breast cancer MCF-7 cells for 24 h or 48 h, as a low concentration group of EGB, a medium concentration group of EGB, and a high concentration group of EGB. Breast cancer MCF-7 cells without intervention were taken as control group. Cell proliferation was measured using MTT assay; Flow cytometry was used to detect cell apoptosis; Immunofluorescence assay was used to determine the contents of prostacyclin (P62), microtubule-associated protein light chain 3Ⅱ (LC3Ⅱ), and caspase-3; The levels of multidrug resistance-associated protein 1 (MRP1), multidrug resistance gene 1 (MDR1) and breast cancer resistance protein (BCRP) were identified by PCR; Western blotting was used to detect the expression of extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase (MAPK), p-ERK, and p-MAPK proteins in cells.Results:The results of MTT assay for cell proliferation showed that cell proliferation at 24 h in control group, EGB low, medium and high concentration groups were 0.95±0.14, 0.65±0.09, 0.51±0.07, 0.37±0.04, respectively, with a statistically significant difference ( F=43.13, P<0.001), cell proliferation at 48 h were 1.32±0.19, 0.54±0.08, 0.32±0.05, 0.15±0.02, respectively, with a statistically significant difference ( F=141.30, P<0.001). Compared with 24 h, cell proliferation was decreased in EGB low, medium and high concentration groups at 48 h (all P<0.05). Pairwise comparison showed that EGB treatment significantly decreased MCF-7 cell viability and cell proliferation was decreased in turn at 24 and 48 h in control group, low, medium, high EGB groups (all P<0.05). Flow cytometry analysis revealed that the apoptosis rates of MCF-7 cells in control group, EGB low, medium and high concentration groups were 2.12%±0.23%, 9.28%±0.45%, 15.17%±1.28% and 22.21%±2.32%, respectively, with a statistically significant difference ( F=128.80, P<0.001). Pairwise comparison showed that the apoptosis rate of control group, EGB low, medium and high concentration groups were increased in turn (all P<0.05). The results of immunofluorescence assay showed that the protein relative expression levels of P62 protein in MCF-7 cells of control group, EGB low, medium and high concentration groups were 3.34±0.52, 2.85±0.47, 2.02±0.18 and 1.08±0.21, respectively, with a statistically significant difference ( F=41.55, P<0.001). LC3Ⅱ protein relative expression levels were 0.24±0.05, 1.02±0.14, 1.47±0.26, 1.95±0.21, respectively, with a statistically significant difference ( F=94.82, P<0.001). The relative expression levels of caspase-3 protein were 0.25±0.03, 0.68±0.21, 1.12±0.17 and 1.65±0.23, respectively, with a statistically significant difference ( F=68.09, P<0.001). Pairwise comparison showed that LC3Ⅱ and caspase-3 protein expression levels were increased in turn in control group, EGB low, medium and high concentration groups, while P62 protein expression levels were decreased in turn (all P<0.05). The PCR experiment results showed that the MRP1 mRNA level of MCF-7 cells in control group, EGB low, medium and high concentration groups were 1.06±0.14, 0.83±0.18, 0.71±0.11, 0.52±0.08, respectively, with a statistically significant difference ( F=17.41, P<0.001). The mRNA levels of MDR1 were 1.14±0.17, 0.75±0.13, 0.60±0.09, 0.48±0.06, respectively, with a statistically significant difference ( F=34.40, P<0.001). BCRP mRNA levels were 1.09±0.11, 0.88±0.13, 0.69±0.07, 0.57±0.05, respectively, with a statistically significant difference ( F=34.13, P<0.001). Pairwise comparison showed that the levels of MRP1, MDR1 and BCRP mRNA were decreased in turn in control group, EGB low, medium and high concentration groups (all P<0.05). The results of Western blotting showed that the expression of ERK in MCF-7 cells in control group, EGB low, medium and high concentration groups were 2.54±0.38, 1.89±0.25, 1.55±0.21, 1.12±0.16, respectively, with a statistically significant difference ( F=31.18, P<0.001). MAPK expression were 2.47±0.34, 1.96±0.29, 1.63±0.27, 1.20±0.24, respectively, with a statistically significant difference ( F=20.90, P<0.001). p-ERK expression were 2.03±0.29, 1.74±0.21, 1.45±0.11, 1.18±0.24, respectively, with a statistically significant difference ( F=16.31, P<0.001). p-MAPK expression were 2.26±0.47, 1.90±0.41, 1.61±0.33, 1.35±0.16, respectively, with a statistically significant difference ( F=7.01, P=0.002). Pairwise comparison showed that the expressions of ERK, MAPK, p-ERK and p-MAPK in control group, EGB low, medium and high concentration groups were decreased in turn (all P<0.05) . Conclusion:EGB can inhibit the proliferation of breast cancer MCF-7 cells, promote the apoptosis of MCF-7 cells, decrease the expression of P62 protein, increase the expression of LC3Ⅱ and caspase-3 protein, induce mitochondrial autophagy.