ObjectiveTo investigate the effects of rhizosphere organic acids secreted by the roots of Salvia miltiorrhiza on continuous cropping obstacles. MethodsThe mixed solution of organic acids in the rhizosphere of S. miltiorrhiza in continuous cropping and rotation cropping was added to the hairy roots subcultured for 21 days， and samples were collected on days 0， 2， 4， 6， 8， and 10. The changes of biomass， effective components， primary metabolites， secondary metabolites， antioxidant enzymes， and hormones in hairy roots of S. miltiorrhiza were observed and determined. ResultsCompared with the rotation cropping group and the blank control group， the simulation of organic acid secretion from the roots of S. miltiorrhiza had a significant inhibitory effect on the growth of hairy roots and decreased the content of effective components as well as total sugar and total protein in primary metabolites. Compared with the blank control group， the rotation cropping group and the continuous cropping group showed total sugar and total protein content decreases of 33.9% and 5.1%， respectively. On the other hand， the secretion of organic acids from S. miltiorrhiza roots significantly promoted the accumulation of total phenolic acids and total tanshinone， which showed increases of 14.6% and 1.6%， respectively， in continuous cropping group and rotation cropping group compared with the blank control group. ConclusionThe organic acid environment under continuous cropping significantly inhibited the growth of hairy roots and the accumulation of primary metabolites， while promoting the synthesis and accumulation of secondary metabolites of S. miltiorrhiza.

Objective To investigate the role and mechanism of circular RNA(circRNA)has_circ_0003304(circAZIN1)in regulating chondrocyte degeneration in osteoarthritis(OA).Methods Gene chip was used to detect the expression level of circRNA during the chondrogenic differentiation of human adipose-de-rived stem cells(hADSC).The circAZIN1 was further screened through the chondrocyte inflammation model constructed with interleukin-β(IL-β)and tumor necrosis factor-α(TNF-α)from the top 10 circRNAs with the most differentiated expression detected by gene chip.Real-time fluorescence quantitative polymerase chain re-action PCR(qPCR)was used to detect the effect of circAZIN1 overexpression(transfected with pcDNA3.1-circAZIN1-EF1-ZsGreen plasmid)on the metabolism of chondrocyte extracellular matrix(ECM).RNA-Pull down test was conducted to detect the protein bound by circAZIN1,miRNA-circRNA Interactions predicted the microRNAs(miRNAs)and their sites that circAZIN1 may be sponge-adsorbed,further TargetMiner,miRDB and TargetScan databases were applied to predict miRNAs which circAZIN1 may sponge-adsorbed.circAZIN1,miRNA and downstream mRNA were detected to find whether there was mirror regulation phe-nomenon after overexpression of miRNA.Results CircAZIN1 had the most significant differential expression during the chondrogenic differentiation of hADSC(day 3 and day 21)and in the chondrocyty inflammation model constructed by IL-β,TNF-α(day 3 group vs.day 21 group,the conttrol group vs.the IL-β group,the control group vs.the TNF-α group).Overexpression of circAZIN1 could promote the ECM synthesis in chon-drocytes and inhibit its decomposition.RNA-Pull down test result showed that circAZIN1 obviously bound AGO2 protein,suggesting that circAZIN1 had a high possibility of sponge adsorbing miRNAs.Further data-base predicted that its downstream was hsa-miR-654-3p,and the downstream mRNA of hsa-miR-654-3p was CACNA1I.After the overexpression of hsa-miR-654-3p,qPCR test found that circAZIN1,hsa-miR-654-3p and CACNA1I had a mirror image regulation phenomenon.Conclusion circAZIN1 inhibits the silencing effect of CACNA1I through sponge adsorption of hsa-miR-654-3p and thus plays a role in inhibiting chondrocyte de-generation,which provides a reference for the study of the regulatory mechanism of circRNA in the develop-ment of OA.

This Practice Guidance intends to coalesce best practice recommendations for the identification of portal hypertension （PH）， for prevention of initial hepatic decompensation， for the management of acute variceal hemorrhage （AVH）， and for reduction of the risk of recurrent variceal hemorrhage in chronic liver disease. The most significant changes in the current Guidance relate to recognition of the concept of compensated advanced chronic liver disease， codification of methodology to use noninvasive assessments to identify clinically significant PH （CSPH）， and endorsement of a change in paradigm with the recommendation of early utilization of nonselective beta-blocker therapy when CSPH is identified. The updated guidance further explores potential future pharmacotherapy options for PH， clarifies the role of preemptive transjugular intrahepatic portosystemic shunt in AVH， discusses more recent data related to the management of cardiofundal varices， and addresses new topics such as portal hypertensive gastropathy and endoscopy prior to transesophageal echocardiography and antineoplastic therapy.

Major research efforts in liver cancer have been devoted to increasing the efficacy and effectiveness of surveillance for hepatocellular carcinoma (HCC). As with other cancers, surveillance programmes aim to detect tumors at an early stage, facilitate curative-intent treatment, and reduce cancer-related mortality. HCC surveillance is supported by a large randomized controlled trial in patients with chronic hepatitis B virus infection and several cohort studies in cirrhosis; however, effectiveness in clinical practice is limited by several barriers, including inadequate risk stratification, underuse of surveillance, and suboptimal accuracy of screening tests. There are several proposed strategies to address these limitations, including risk stratification algorithms and biomarkers to better identity at-risk individuals, interventions to increase surveillance, and emerging imaging- and blood-based surveillance tests with improved sensitivity and specificity for early HCC detection. Beyond clinical validation, data are needed to establish clinical utility, i. e. increased early tumor detection and reduced HCC-related mortality. If successful, these data could facilitate a precision screening paradigm in which surveillance strategies are tailored to individual HCC risk to maximise overall surveillance value. However, practical and logistical considerations must be considered when designing and implementing these validation efforts.To address these issues, the International Liver Cancer Association (ILCA) adjourned a single topic workshop on HCC risk stratification and surveillance in June 2022. Herein, we present a white paper on these topics, including the status of the field, ongoing research efforts, and barriers to the translation of emerging strategies.

This article is an excerpt from the Expert Management of Congenital Portosystemic Shunts and Their Complications, which was published by the European Association for the Study of the Liver (EASL). Some of the most challenging systemic complications that often associated with congenital portosystemic shunts (CPSS) are liver nodules, pulmonary hypertension, endocrine abnormalities, and neurocognitive dysfunction. This article mainly provides expert clinical guidance for the management of liver nodules, pulmonary hypertension, and endocrine abnormalities, along with recommendations for shunt closure and follow-up.

Acute variceal bleeding (AVB) continues to be a fatal complications of cirrhotic portal hypertension. Although the hospitalization rate of patients with acute variceal bleeding has significantly decreased with the advancement of medical technology, and the mortality rate has dropped from 50% three decades before to 15%～20% now, the in-hospital mortality rate is still high and is closely related to the severity of cirrhosis, ranging from 0 in Child A grade to 32% in Child C grade. Therefore, it is a good choice to risk stratify these patients and individualize the treatment method according to the expected risk, as the risk of death in patients with acute variceal bleeding is highly heterogeneous. This article mainly reviews the current status of risk stratification and treatment of acute variceal bleeding in cirrhosis.

Liver diseases in pregnancy comprise both gestational liver disorders and acute and chronic hepatic disorders occurring coincidentally in pregnancy.Whether pregnancy-related or not,liver diseases in pregnancy are associated with a significant risk of maternal and fetal morbidity and mortality.Thus,the European Association for the Study of the Liver invited a panel of experts to develop clinical practice guidelines aimed at providing recommendations,based on the best available evidence,for the management of liver diseases in pregnancy for hepatologists,gastroenter-ologists,obstetric physicians,general physicians,training specialists and other healthcare professionals who provide care for this patient population.

Acute-on-chronic liver failure(ACLF),which was first described in 2013,is a severe form of acutely decompensated cirrhosis characterized by the existence of organ system failure(s)and a high risk of short-term mortality.ACLF is caused by an excessive systemic inflammatory response triggered by precipitants that are clinically apparent(e.g.,confirmed microbial infection with sepsis,severe alcohol-related hepatitis)or not.Since the description of ACLF,some important studies have suggested that patients with ACLF may benefit from liver transplantation and should therefore be urgently stabilized for transplantation by receiving appropriate etiological treatment and comprehensive management,including support of organ systems in the intensive care unit(ICU).The goal of the present clinical practice guidelines is to provide the most reliable evidence available to assist the clinical decision-making process in the management of patients with ACLF,to make triage decisions(ICU vs.no ICU),to identify and manage acute precipitants,to identify organ systems that require support or replacement,to define potential criteria for futility of intensive care,and it also provides suggestions for identifying potential indications for liver transplantation.

Liver function can reflect the severity of cirrhosis,and has important clinical value for disease monitoring,efficacy evaluation and surgical risk prediction.At present,the methods commonly used in clinical evaluation of liver function include blood biochemical examination,drug excretion test,comprehensive scoring system and routine imaging examination.All these methods have their limitations.Gd-EOB-DTPA is a hepatocellular specific contrast agent,which is taken up and excreted by liver cells and can directly reflect liver function.Therefore,it is expected to achieve non-invasive segental quantitative evaluation of liver function through enhanced MRI of Gd-EOB-DTPA,which is the focus of current research.In this paper,the methods of Gd-EOB-DTPA enhanced MRI for liver function assessment were reviewed,and the feasibility of Gd-EOB-DTPA in liver function assessment was discussed.

Acute-on-chronic liver failure (ACLF), which was first described in 2013, is a severe form of acutely decompensated cirrhosis characterised by the existence of organ system failure(s) and a high risk of short-term mortality. ACLF is caused by an excessive systemic inflammatory response triggered by precipitants that are clinically apparent (e.g., comfirmed microbial infection with sepsis, severe alcohol-related hepatitis) or not. Since the description of ACLF, some important studies have suggested that patients with ACLF may benefit from liver transplantation and should therefore be urgently stabilized for transplantation by receiving appropriate etiological treatment and comprehesive management, including support of organ systems in the intensive care unit (ICU). The goal of the present clinical practice guidelines is to provide the most reliable evidence available to assist the clinical decision-making process in the management of patients with ACLF, to make triage decisions (ICU vs. no ICU), to identify and manage acute precipitants, to identify organ systems that require support or replacement, to define potential criteria for futility of intensive care, and it also provides suggestions for identifying potential indications for liver transplantation.