Acute-on-chronic liver failure (ACLF) is an acute decompensated syndrome that occurs on the basis of chronic liver disease, with rapid disease progression and poor prognosis, thus being an important cause of death in patients with cirrhosis. Predisposing factors play an important role in the occurrence, progression and prognosis of ACLF, which are heterogeneous in different definitions and regions. With the development of medical and health services and changes in lifestyles, the composition of predisposing factors also changes. These factors cause damage to organ function in various ways, leading to different types of organ failure and prognosis. Early warning of the predisposing factors can prevent the occurrence of ACLF. Actively removing predisposing factors can improve the prognosis of ACLF. Reasonable management of precipitating factors is important for ACLF.

Liver cirrhosis is the end stage of chronic liver diseases with various complications, thereby imposing great burden to the patient's family and public health care. Abnormal nutritional status, mainly including malnutrition and overnutrition(overweight/obesity), are related to the occurrence of many chronic liver diseases, and have major impact on the progression and outcome of liver cirrhosis. Nutritional status of cirrhotic patients should be comprehensively assessed based on various factors, including underlying diseases, diet, clinical manifestations, and laboratory tests, etc. Cirrhotic patients with malnutrition should receive individualized nutritional support therapy in timely fashion, and those with overweight/obesity should undergo dietary intervention or physical activity to improve the quality of life and reduce the risk of death.

Portal vein thrombosis (PVT) is a common complication of liver cirrhosis. Decreased portal vein velocity is the most important risk factor for cirrhotic PVT, and the etiology and severity of liver cirrhosis, hemostasis status, and inflammatory and immune mechanisms may also be associated with the development of cirrhotic PVT. The natural history of cirrhotic PVT includes improvement, stabilization, progression, and recurrence. Non-occlusive PVT and improvement of liver function may be associated with spontaneous improvement of cirrhotic PVT. The impact of different occlusion degree of cirrhotic PVT on patients' prognosis is inconsistent. Non-occlusive PVT may not significantly affect patients' outcomes; occlusive PVT may increase the risk of death, and PVT involving the mesenteric veins may also lead to intestinal ischemia and infarction. Clinical management strategies for cirrhotic PVT include wait-and-see strategy (no intervention), anticoagulation, thrombolysis, and transjugular intrahepatic portosystemic shunt (TIPS). When the degree of PVT is less than 50% and the mesenteric veins are not involved, immediate intervention may not be required. Anticoagulation is the first-line choice for cirrhotic PVT requiring treatment. Thrombolysis and TIPS are mainly used for patients with contraindications of anticoagulation and those who do not respond to anticoagulation. This paper reviews the clinical assessment of cirrhotic PVT and its predictors, natural history, impact on prognosis, treatment, and prophylaxis.

Objective To investigate the effect of ROCK inhibitor fasudil (FS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and its possible mechanisms. Methods Forty male C57BL/6 mice were randomly divided into four groups (n=10): control group, ALI group, FS group, and ALI+FS group. After administration of LPS or FS, lung histopathological changes, inflammatory cytokine levels, expression levels of Rho kinase (ROCK), and cell pyroptosis-related proteins, including NLRP3, ASC, caspase-1, cleaved caspase-1, GSDMD, cleaved GSDMD, and IL-1β, were assessed. In vitro, human umbilical vein endothelial cells (HUVECs) were cultured and the cell activity, LDH release rate, inflammatory factor levels, and the expression levels of cell pyroptosis-related proteins were measured after administration of LPS+ATP and FS. Results In vivo experiments on mice demonstrated that the alveolar hemorrhage, alveolar septum thickening, and lung tissue edema were more pronounced in ALI group compared to the control group, and FS pretreatment significantly reduced these histopathological changes. Compared with the control group, mice in ALI group showed increased lung wet/dry weight ratio, increased total cell count and total protein concentration in alveolar lavage fluid, increased levels of TNF-α, IL-6, IL-18, and IL-1β, and increased expression of ROCK1, ROCK2, and pyroptosis-related proteins including NLRP3, ASC, cleaved caspase 1, cleaved GSDMD, and IL-1β in pulmonary tissues (P<0.05); compared with mice in ALI group, mice in ALI+FS group had a lower lung wet/dry weight ratio, a lower total cell count and total protein concentration in alveolar lavage fluid, lower levels of inflammatory factors and lower expression levsls of ROCK1, ROCK2, and pyroptosis-related proteins in lung tissue (P<0.05). In vitro experiments on HUVECs cells confirmed that compared with the control group, ALI group showed a significant decrease in cell viability, an increase in LDH release rate, cell death rate, and inflammatory factor levels, and an upregulation of the expression of the pyroptosis-related proteins (P<0.05); compared with ALI group, ALI+FS group showed an increase in cell viability, a significant decrease in LDH release rate, cell death rate, and inflammatory factor levels, and downregulation of the expression of pyroptosis proteins (P<0.05). Conclusion FS may alleviate LPS-induced ALI by inhibiting endothelial cell pyroptosis.

Objective To investigate the effect and mechanism of Yes-associated protein (YAP) on rat cardiac fibroblasts(CFs) proliferation and transdifferentiation induced by high glucose. Methods The CFs cells were isolated and cultured of newborn SD rats aged 1-3 days, then treated with 40 mmol/L D-glucose for concentration of diabetes cardiomyopathy model(DCM), and the relative expression levels were detected with Western blotting of YAP, α-smooth muscle actin (α-SMA), collagenⅠ, collagen Ⅲ and connective tissue growth factor (CTGF), respectively, at the time points 24 hours. The CFs cells were divided into normal glucose (NG) control group (5.5 mmol/L D-glucose), high glucose (HG) group (40.0 mmol/L D-glucose), normal glucose +0.5 μmol/L verteporfin (NG+VP) group and high glucose + 0.5 μmol/L verteporfin (HG+VP) group. Verteporfin is an inhibitor of YAP, which blockades the interaction between YAP and TEAD. Immunofluorescence of vimentin was used to identify CFs. Immunofluorescence of Ki-67 was used to detect the proliferation activities of CFs in various groups. Western blotting was performed to detect the levels of α-SMA, collagen Ⅰ and collagen Ⅲ, YAP and CTGF proteins in CFs of various groups. Results The positive result of vimentin immunofluorescence prompted that the primary cultured cells were rat's CFs. Immunofluorescence of Ki-67 showed that, the positive rate (%) of Ki-67 in CFs was obviously higher in HG group than in NG group (67.33±5.14 vs. 22.94±4.88, P<0.05); After treatment with VP, the positive rate (%) of Ki-67 in CFs decreased markedly (46.83±3.86 vs. 67.33±5.14, P<0.05). Western blotting showed that, compared with NG group, the relative expression levels of α-SMA, collagenⅠ and collagen Ⅲ in CFs increased significantly in HG group (1.43±0.98 vs. 0.93±0.06, 1.80±0.09 vs. 1.08±0.09, 1.43±0.09 vs. 0.88±0.10, P<0.05), and the relative expression levels of VAP and CTGF protein also increased (1.93±0.15 vs. 1.17±0.09, 1.80±0.18 vs. 1.23±0.16, P<0.05). Compared with the HG group, the relative expression levels of α-SMA, collagen I, collagen Ⅲand CTGF proteins decreased significantly in HG+VP group (1.27±0.06 vs. 1.71±0.12, 2.05±0.23 vs. 3.03±0.17, 1.10±0.12 vs. 1.82±0.18, 1.31±0.16 vs. 1.57±0.03, P<0.05), while compared with NG group, the relative expression levels of α-SMA, collagen Ⅰ and CTGF proteins were higher in HG+VP group (P<0.05). Conclusion High glucose promotes the proliferation and activation of neonatal rats CFs and excessive synthesis of extracellular matrix proteins such as collagen by regulating the YAP/TEAD/CTGF signaling pathway.

Objective To explore the effect of miR-491-5p on the apoptosis of trophoblast cells induced by hypoxia and the process of preeclampsia. Methods Human trophoblast cells were divided into control group, hypoxia group, hypoxia+miR-491-5p mimic group and hypoxia+miR-491-5p inhibit group. Cell viability staining was used to detect hypoxia-induced trophoblast cell apoptosis. qRT-PCR was used to detect the expression of miR-491-5p in hypoxia-induced trophoblast cells; TargetScan database to predict miR-491-5p target; Detection of dual-luciferase reporter gene was used to confirm the targeting relationship between miR-149-5p and BCL2l2; miR-491-5p mimic and inhibitor single-stained embryonic trophoblast cells, qRT-PCR was used to detect the expression of miR-491-5p. Western blotting was used to detect changes of BCL2l2 expression in trophoblast after overexpression and inhibition of miR-491-5p; cell viability staining, Western blotting, and flow cytometry to detect trophoblast apoptosis. Results Compared with control group, the hypoxia group had significantly increased cell apoptosis and increased expression of miR-491-5p (2.784±0.214 vs. 1.000±0.000, P<0.01); bioinformatics detection and dual luciferase detection report experiments showed that miR-491-5p can targete and regulate BCL2l2 expression. Compared with control group, the miR-491-5p content in hypoxia+miR-491-5p mimic group was significantly increased (7659.300±191.300 vs. 5.467±0.503, P<0.05), while that in miR-491-5p inhibit group was the opposite (0.139±0.022 vs. 0.323±0.035, P<0.01). Compared with hypoxia group, the apoptosis rate of trophoblast cells was decreased (11.56%±0.452% vs. 16.67%±0.750%, P<0.01), the expressions of BCL2L2 (0.702±0.047 vs. 0.312±0.007, P<0.001) and Bcl-2 (0.752±0.055 vs. 0.415±0.005, P<0.01) were increased, and the expression of Bax (1.221±0.066 vs. 1.652±0.085, P<0.01) was decreased in hypoxia+miR-491-5p inhibit group; but in hypoxia+miR-491-5p mimic group, the apoptosis rate was increased (23.54%±1.233% vs. 16.67%±0.750%, P<0.001), the contents of BCL2L2 (0.211±0.013 vs. 0.312±0.007, P<0.01) and Bcl-2 (0.203±0.011 vs. 0.415±0.005, P<0.001) was decreased, and Bax (2.362±0.284 vs. 1.652±0.085, P<0.01) expression was increased. Conclusions miR-491-5p might negatively regulates the expression of BCL2L2, increases the apoptosis of trophoblast cells induced by hypoxia and accelerates the development of preeclampsia.

Objective To investigate the action mechanism of Xibining decoction on mitigation of pain of knee osteoarthritis (KOA) through regulation of redox homeostasis of synoviocytes by carnitine palmitoyl transferase 1 (CPT1) enzyme. Methods Fibroblast-like synovial cells (FLS) were extracted from rats' knee joint and the optimal concentration of the freeze-dried powder of Xibining decoction on FLS was selected by CCK-8. Subsequently, the cells were divided into control group, KOA group and Xibining group. The inflammatory environment of KOA was induced by 5 μg/ml lipopolysaccharide (LPS) in the last two groups, and in Xibining group, 100 μg/ml Xibining were added and cultured for 24 hours. The mRNA and protein expressions of CPT1 and carnitine/organic cation transporters 1 (OCTN1) were detected by Real-time PCR and Western blotting. The activities of CPT1 and superoxide dismutase (SOD) and malondialdehyde (MDA) content were detected by assay kits. Reactive oxygen species(ROS) level was detected by a 2',7'-dichlorofluorescein diacetate assay. The dorsal root ganglion (DRG) neurons were extracted from rats and identified by βⅢ-tubulin and glial fibrillary acidic protein (GFAP) immunofluorescence. The neurons were divided into control group, KOA group and Xibining group, the FLS supernatants of the three groups were added to the DRG for 24 hours. The mRNA and protein expression of transient receptor potential A1 ion channel (TRPA1) were detected by Real-time PCR and Western blotting. Ca²⁺ influx in DRG neurons after TRPA1 opening was observed by Real-time fluorescent calcium imaging. ELISA assay was used to detect the content of calcitonin gene related peptide (CGRP) and substance P (SP) in DRG supernatant. Results The ideal freeze-dried powder of Xibining decoction concentration was identified as 100 μg/ml. Real-time PCR and Western blotting results showed that the expression levels of mRNA and protein in CPT1 and OCTN1 of Xibining group were significantly higher than those in KOA group (P<0.05). Compared with control group, the average fluorescence intensity and MDA contents increased significantly in KOA group [(5.52±0.78) AU vs. (26.46±2.07) AU; (2.77±0.03) nmol/ml vs. (3.13±0.02) nmol/ml] (P<0.05); the activities of CPT1 and SOD were significantly downregulated [(11.50±0.21) nmol/min vs. (4.98±0.02) nmol/min; (17.6±0.07) U/ml vs. (11.38±0.05) U/ml] (P<0.05). Compared with KOA group, the fluorescence intensity and MDA contents significantly decreased in Xibining group [(14.07±1.41) AU and (2.87±0.01) nmol/ml] (P<0.05), the activities of CPT1 and SOD [(7.94±0.21) nmol/min and (13.81±0.07) U/ml] were significantly upregulated (P<0.05). Compared with KOA group, after treatment with FLS supernatant in Xibining group, the mRNA and protein expression of TRPA1, and Ca²⁺ influx after TRPA1 opening were inhibited in DRG (P<0.05). In addition, the expression of CGRP and SP were also reduced in Xibining group [(19.93±1.2) ng/L vs. (30.19±1.58) ng/L, P<0.05; (84.23±1.26) ng/L vs. (123.16±2.95) ng/L, P<0.05]. Conclusion Xibining can regulate the local redox homeostasis of FLS through CPT1 enzyme, which can further influence the Ca²⁺ influx on the TRPA1 ion channel of DRG and reduce the secretion of pain factor to alleviate KOA pain.

Objective To investigate the effect and mechanism of Paris saponins on iron death in triple negative breast cancer cells. Methods MDA-MB-231 cells were treated with 0, 10, 20, 30, 40 and 50 μmol/L of Paris saponins. Cell viability was detected by CCK-8 method. MDA-MB-231 cells at logarithmic growth stage were randomly divided into control group, Paris saponin group (treated with 30 μmol/L Paris saponin for 12 h), inhibitor group (treated with 2 μmol/L Ferrostatin for 12 h) and Paris saponin + inhibitor group (treated with 30 μmol/L Paris saponin for 12 h after treatment with 2 μmol/L Ferrostatin-1 for 12 h), cell viability was detected by CCK-8 method, cell apoptosis rate was detected by flow cytometry. The expressions of divalent metal ion transporter 1 (DMT1), transferrin receptor 1 (TFR1), glutathione peroxidase 4 (GPX4), p53 and p53/SLC7A11 were detected by qRT-PCR and Western blotting. Results CCK-8 assay showed that the survival rate of MDA-MB-231 cells was decreased with the increase of the concentration of Paris saponin in a dose-dependent manner (P<0.05). Compared with control group, the cell survival rate, the relative expression levels of CPX4, SLC7A11 mRNA and protein decreased, while of apoptosis rate, the relative, expression levels of TFR1, DMT1, p53 mRNA and protein increased in Paris saponin group, the relative expression levels of CPX4, SLC7A11 mRNA and protein increased in inhibitor group, the apoptosis rate and the relative expressions of TFR1, DMT1 and p53 mRNA and protein were decreased (P<0.05). Compared with inhibitor group, the cell survival rate and the mRNA and protein relative expressions of CPX4 and SLC7A11 decreased, while the apoptosis rate and the mRNA and protein relative expressions of TFR1, DMT1 and p53 increased in parisaponin + inhibitor group (P<0.05). Conclusion Paris saponin inhibits the proliferation of triple negative breast cancer cells and promotes iron death in cancer cells, possibly through the regulation of p53/SLC7A11 signal axis.

Objective To explore the alternative value of internal jugular vein collapsibility index (IJVCI) and subclavian vein collapsibility index (SCVCI) used to substitute for inferior vena cava collapsibility index (IVCCI) in volume evaluation under spontaneous breathing and mechanical ventilation. Methods A total of 100 patients were selected who underwent elective surgery in the Department of Anesthesiology, the First Affiliated Hospital of Chongqing Medical University from December 2020 to August 2021, the cyclic indicators of patients with different respiratory states were compared. According to the cut-off value of IVCCI, the patients were divided into hypovolemic group and non-hypovolemic group, and the cyclic indicators of the two groups were compared under different respiratory states. Pearson correlation analysis and Bland-Altman analysis were used to determine the relevance and consistency between IJVCI, SCVCI and IVCCI. ROC curve was used to analyze the efficiency of IJVCI and SCVCI in volume evaluation. Results Under mechanical ventilation condition, compared to spontaneous breathing condition, the SpO₂ of patients was obviously increased, and heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), IVCCI, IJVCI and SCVCI were significantly decreased (P<0.01). IJVCI and SCVCI in non-hypovolemic group were significantly lower than those in hypovolemic group under the condition of spontaneous respiration (P<0.001). Under the condition of mechanical ventilation, SBP in non-hypovolemic group was significantly increased than that in hypovolemic group (P<0.05), while IJVCI and SCVCI were significantly lower than those in hypovolemic group (P<0.001). Under the condition of spontaneous breathing and mechanical ventilation, there was a significant positive correlation and consistency between IJVCI and IVCCI (r=0.586, P<0.01; r=0.514, P<0.001), and that a significant positive correlation and consistency between SCVCI and IVCCI (r=0.385, P<0.01; r=0.521, P<0.01). The area under the ROC curve (AUC) of IJVCI and SCVCI for the diagnosis of hypovolemia was 0.828, 0.684, and the best cut-off value was 22.2%, 25.4% under the condition of spontaneous breathing. The AUC of hypovolemia diagnosed by IJVCI and SCVCI were 0.701, 0.773, and the best cut-off value was 19.8%, 13.2% under the condition of mechanical ventilation. Conclusion Both IJVCI and SCVCI can replace IVCCI for volume evaluation in different respiratory states, but the alternative value of IJVCI is higher in spontaneous breathing state while of SCVCI is higher in mechanical ventilation state for volume evaluation.

Objective To explore the application value of routine electrocardiogram in the diagnosis of left ventricular hypertrophy (LVH) in hypertensive patients using different configuration diagnostic criteria. Methods The clinical data were collected of 228 patients with essential hypertension treated in Qilu Hospital of Shandong University from September 2016 to March 2021, and the results of echocardiography and electrocardiogram were retrospectively analyzed. Ganau classification of left ventricle was done according to 2018 European Society of Cardiology (ESC)/European Society of Hypertension (ESH) criteria. The patients were divided into normal configuration (NG, n=58) group, concentric remodeling (CR, n=107) group, eccentric hypertrophy (EH, n=24) group and concentric hypertrophy (CH, n=39) group. The classification was done again according to the Echocardiographic Measurements in Normal Chinese Adults (EMINCA) criteria, patients were divided into NG group (n=105), CR group (n=27), EH group (n=81) and CH group (n=15). The consistency of the results of left ventricular configuration classification according to different criteria was compared, and the diagnostic value of ECG in different left ventricular configuration and the difference between groups were analyzed. Results The results of configuration classified according to the 2018 ESC/ESH criteria and EMINCA criteria had statistical difference (P<0.01), and the consistency was poor (Kappa=0.330, P<0.01). According to the 2018 ESC/ESH criteria, the positive rate of ECG in NG group, CR group, EH group and CH group were 5.2%, 7.5%, 29.2%, and 30.8%, respectively. The differences among groups were statistically significant (P<0.01). The positive rate of EH group or CH group was significantly higher than that in NG group or CR group (P<0.0083). The sensitivity and specificity of ECG in diagnosing LVH were 30.2% and 93.3%, respectively. According to the EMINCA criteria, the positive rate of ECG in diagnosing LVH in NG group, CR group, EH group and CH group were 1.9%, 3.7%, 25.9%, and 40.0% respectively. The differences among groups were statistically significant (P<0.01). The positive rate in EH and CH group was significantly higher than that in in NG group (P<0.0083). The sensitivity and specificity of ECG in diagnosing LVH were 28.1% and 97.7%, respectively. Conclusions 2018 ESC/ESH criteria and EMINCA criteria showed a significant difference in classification of left ventricular configuration. In the two different criteria, ECG has low sensitivity and high specificity in the diagnosis of LVH.