Aim To determine the tolerance and acceptance of hepatic venous pressure gradient (HVPG) measurements in patients with liver cirrhosis. Methods This prospective international multicenter study included 271 patients with cirrhosis who were scheduled to undergo HVPG measurement between October 2019 and June 2020. Data related to the tolerance and acceptance of HVPG measurements were collected using descriptive questionnaires. Results HVPG measurements were technically successful in all 271 patients, with 141 (52.0%) undergoing HVPG measurement alone. The complication rate was 0.4%. Postoperative pain was significantly lower than preoperative expected pain (p < 0.001) and intraoperative pain (p < 0.001), and intraoperative pain was also significantly lower than preoperative expected pain (p = 0.036). No, mild, moderate, severe, and intolerable discomfort scores were reported by 36.9%, 44.6%, 11.1%, 6.3%, and 0.4% of these patients, respectively, during HVPG measurement and by 54.6% 32.5%, 11.4%, 1.5%, and 0%, respectively, after HVPG measurement. Of these patients, 39.5% had little understanding and 10% had no understanding of the value of HVPG measurement, with 35.1% and 4.1% regarding HVPG measurements as being of little or no help, respectively. Most patients reported that they would definitely (15.5%), probably (46.9%), or possibly (29.9%) choose to undergo additional HVPG measurements again, and 62.7% regarded the cost of the procedure as acceptable. Conclusion HVPG measurement was safe and well‐tolerated in patients with cirrhosis, but patient education and communication are warranted to improve the acceptance of this procedure.

Background Skeletal muscle‐secreted myokines widely participate in lipids metabolism through autocrine, paracrine and endocrine actions. The myokines represented by FGF21 and Irisin can promote the browning of adipocytes and serve as promising targets for treating obesity. Although recombinant myokines replacement therapy and AAV (adeno‐associated virus)‐based myokines overexpression have shown a definite effect in ameliorating obesity, novel myokine activation strategies with higher efficacy and safety are still in pressing need. This study aimed to evaluate the therapeutic potential of a novel CRISPR‐based myokines activation strategy in obesity treatments. Methods In this study, we used lentivirus and a single AAV vector containing dCas9‐VP64 with a single‐guide RNA to selectively activate Fgf21 and Fndc5 expression in skeletal muscles both in vitro and in vivo. The activation efficacy of the CRISPRa system was determined by qRT‐PCR, Western blotting and ELISA. The treatment effect of CRISPR‐based myokines activation was tested in 3T3‐L1‐derived adipocytes and diet‐induced obese (DIO) mice (male C57BL/6 mice, induced at 6‐week‐old for 10 weeks). Results The virus upregulates myokines expression in both mRNA and protein levels of muscle cells in vitro and in vivo. Myokines secreted by muscle cells promoted browning of 3T3‐L1‐derived adipocytes. In vivo activation of myokines by AAVs can reduce body weight and fat mass, increase the adipocytes browning and improve glucose tolerance and insulin sensitivity in DIO mice. Conclusions Our study provides a novel CRISPR‐based myokines activation strategy that can ameliorate obesity by promoting adipocytes browning.

Chronic liver disease (CLD) has become a major health problem worldwide owing to its increased morbidity and mortality. Evaluation of the degree of liver injury is crucial for the clinical management and treatment of CLD patients. In the current clinical practice, liver biopsy with histological analysis is the clinical standard for assessing the degree of CLD injury. However, liver biopsy is an invasive procedure that is limited by sampling errors and interobserver variability and is insufficient for screening and monitoring. Advanced three-dimensional magnetic resonance elastography (3D MRE) is a simple, fast, safe, and noninvasive technology. This offers comprehensive insight into increased liver stiffness beyond stage-specific fibrosis. This technology exhibits considerable potential for comprehensively and simultaneously assessing early necroinflammation, discriminating necroinflammation from fibrosis, detecting nonalcoholic steatohepatitis severity, predicting cirrhosis complications, and identifying tumor recurrence. Nevertheless, the clinical application and promotion of this technology are currently required in China. 3D MRE should evolve towards better clinical convenience and satisfaction to provide an imaging basis to improve treatment selection in CLD patients and facilitate its widespread use.