Background::Hepatic ischemia-reperfusion injury (HIRI) remains a common complication during liver transplantation (LT) in patients. As a key downstream effector of the Hippo pathway, Yes-associated protein (YAP) has been reported to be involved in various physiological and pathological processes. However, it remains elusive whether and how YAP may control autophagy activation during ischemia-reperfusion.Methods::Human liver tissues from patients who had undergone LT were obtained to evaluate the correlation between YAP and autophagy activation. Both an in vitro hepatocyte cell line and in vivo liver-specific YAP knockdown mice were used to establish the hepatic ischemia-reperfusion models to determine the role of YAP in the activation of autophagy and the mechanism of regulation. Results::Autophagy was activated in the post-perfusion liver grafts during LT in patients, and the expression of YAP positively correlated with the autophagic level of hepatocytes. Liver-specific knockdown of YAP inhibited hepatocytes autophagy upon hypoxia-reoxygenation and HIRI ( P <0.05). YAP deficiency aggravated HIRI by promoting the apoptosis of hepatocytes both in the in vitro and in vivo models ( P <0.05). Attenuated HIRI by overexpression of YAP was diminished after the inhibition of autophagy with 3-methyladenine. In addition, inhibiting autophagy activation by YAP knockdown exacerbated mitochondrial damage through increasing reactive oxygen species ( P <0.05). Moreover, the regulation of autophagy by YAP during HIRI was mediated by AP1 (c-Jun) N-terminal kinase (JNK) signaling through binding to the transcriptional enhanced associate domain (TEAD). Conclusions::YAP protects against HIRI by inducing autophagy via JNK signaling that suppresses the apoptosis of hepatocytes. Targeting Hippo (YAP)-JNK-autophagy axis may provide a novel strategy for the prevention and treatment of HIRI.

Objective:To analyze the influence of vitamin D 3 supplementation on the clinical efficacy of mesalazine in patients with ulcerative colitis (UC). Methods:From January 2015 to December 2020, patients with mild-to-moderate active UC were retrospectively and continuously enrolled, who accepted mesalazine treatment for at least 12 months at the Second Affiliated Hospital of Wenzhou Medical University. According to simultaneous supplement of vitamin D 3 (125 IU/d), the patients were divided into study group and control group. Demographic and disease characteristics, serum 25-hydroxyvitamin D[25(OH)D] levels and other information were collected through retrieving hospital database. Student′s t-test, Mann-Whitney U test and Chi-square test were applied for comparison of disease characteristics. The changes of modified Mayo scores[ΔMayo] and 25(OH)D[Δ25(OH)D] were compared before and after treatment by paired t-test, Wilcoxon signed rank test and Chi-square test. Multiple linear regression model was used to analyze the independent factors affecting ΔMayo and Δ25(OH)D, and variables with P-values less than 0.20 in the univariate analysis were allowed for further multivariate analysis. Results:A total of 74 UC patients (44 males, 30 females), with median age (range) 39.5 (20-76) years old, were analyzed and respectively assigned into study group ( n=36) and control group ( n=38). In study group, the average level of serum 25(OH)D was significantly increased at month 12 compared with that at baseline [(22.87±7.30) μg/L vs. (18.15±7.48) μg/L, P<0.001]. However, no significant elevation of serum 25(OH)D was found in control group [(19.17±8.49) μg/L vs. (19.82±9.47) μg/L, P=0.466]. Furthermore, there was a significant decrease of modified Mayo score [-3(-4.75, -1.25) vs.-2(-3.25, 0), P=0.034] and a higher clinical remission rate (55.6% vs. 28.9%, P=0.020) at month 12 in study group than those in control group. In addition, according to the baseline level of serum 25(OH)D before mesalazine treatment, 74 UC patients were divided into vitamin D deficiency group ( n=38, serum 25(OH)D<20 μg/L) and non-deficiency group ( n=36, serum 25(OH)D≥20 μg/L). At month 12 in vitamin D deficiency group, patients with vitamin D3 supplementation had a greater decline in modified Mayo score [-4(-5.75, -2) vs.-2(-4, 0), P=0.048] and a higher clinical remission rate (60.0% vs. 22.2%, P=0.019) compared with those without. Conclusions:In patients with mild-to-moderate active UC receiving mesalazine treatment, vitamin D3 supplementation may improve the clinical efficacy, especially in patients with vitamin D deficiency.

Objective To establish an acute rejection model of cervical heart transplantation in mice and evaluate the survival and dynamic rejection process post-transplantation. Methods Mice were randomly divided into sham operation group (n=10), syngeneic transplantation group (n=21), and allogeneic transplantation group (n=65). Sham operation, syngeneic cervical heart transplantation, and allogeneic cervical heart transplantation were performed respectively. The survival of recipient mice and grafts, histopathological changes of graft tissues, subpopulations of splenic lymphocytes, and expression of inflammatory factors in serum and grafts were observed. Results The survival rate and graft survival rate of the sham operation group and syngeneic transplantation group were 100% at 7 days after surgery. In the allogeneic transplantation group, 5 cases failed and died on the first day after surgery. The survival rate at 7 days after surgery was 86%, and all surviving mice had grafts that stopped beating at 7 days after surgery. The allogeneic transplantation group showed significant rejection at 7 days after surgery, accompanied by tissue damage and CD8⁺ T cell infiltration. The proportion of CD8⁺ T cells in the spleen continued to rise post-operation, while the proportion of CD4⁺ T cells showed a downward trend. The expression of interferon-γ in serum and grafts peaked at 5 days after surgery, while the expression of tumor necrosis factor-α showed no statistical significance. Conclusions Acute rejection following heart transplantation in mice intensifies between 5 to 7 days after surgery, which may be a critical time window for immunological intervention.