Sepsis is a life‐threatening organ dysfunction syndrome, and liver is a susceptible target organ in sepsis, because the activation of inflammatory pathways contributes to septic liver injury. Oxidative stress has been documented to participate in septic liver injury, because it not only directly induces oxidative genotoxicity, but also exacerbates inflammatory pathways to potentiate damage of liver. Therefore, to ameliorate oxidative stress is promising for protecting liver in sepsis. Wogonin is the compound extracted from the medicinal plant Scutellaria baicalensis Geogi and was found to exert therapeutic effects in multiple inflammatory diseases via alleviation of oxidative stress. However, whether wogonin is able to mitigate septic liver injury remains unknown. Herein, we firstly proved that wogonin treatment could improve survival of mice with lipopolysaccharide (LPS)‐ or caecal ligation and puncture (CLP)‐induced sepsis, together with restoration of reduced body temperature and respiratory rate, and suppression of several pro‐inflammatory cytokines in circulation. Then, we found that wogonin effectively alleviated liver injury via potentiation of the anti‐oxidative capacity. To be specific, wogonin activated Nrf2 thereby promoting expressions of anti‐oxidative enzymes including NQO‐1, GST, HO‐1, SOD1 and SOD2 in hepatocytes. Moreover, wogonin‐induced Nrf2 activation could suppress NF‐κB‐regulated up‐regulation of pro‐inflammatory cytokines. Ultimately, we provided in vivo evidence that wogonin activated Nrf2 signalling, potentiated anti‐oxidative enzymes and inhibited NF‐κB‐regulated pro‐inflammatory signalling. Taken together, this study demonstrates that wogonin can be the potential therapeutic agent for alleviating liver injury in sepsis by simultaneously ameliorating oxidative stress and inflammatory response through the activation of Nrf2.

Hepatocellular carcinoma (HCC) is the malignancy derived from normal hepatocytes with increasing incidence and extremely poor prognosis worldwide. The only approved first‐line systematic treatment agent for HCC, sorafenib, is capable to effectively improve advanced HCC patients’ survival. However, it is gradually recognized that the therapeutic response to sorafenib could be drastically diminished after short‐term treatment, defined as primary resistance. The present study is aimed to explore the role of stress‐inducible protein Sestrin2 (SESN2), one of the most important sestrins family members, in sorafenib primary resistance. Herein, we initially found that SESN2 expression was significantly up‐regulated in both HCC cell lines and tissues compared to normal human hepatocytes and corresponding adjacent liver tissues, respectively. In addition, SESN2 expression was highly correlated with sorafenib IC ₅₀ of HCC cell lines. Thereafter, we showed that sorafenib treatment resulted in an increase of SESN2 expression and the knockdown of SESN2 exacerbated sorafenib‐induced proliferation inhibition and cell apoptosis. Further mechanistic study uncovered that SESN2 deficiency impaired both AKT and AMPK phosphorylation and activation after sorafenib treatment. Moreover, the correlations between SESN2 expression and both phosphor‐AKT and phosphor‐AMPK expression were illustrated in HCC tissues. Taken together, our study demonstrates that SESN2 activates AKT and AMPK signaling as a novel mechanism to induce sorafenib primary resistance in HCC.

Background: Self-management plays an important role in the disease management of glaucoma patients. The effectiveness of the program can be improved by assessing the patient’s perspective and needs to tailor self-management support. Most studies have focused on assessing one of these self-management behaviours, such as medication adherence, and there is a lack of systematic assessment of the support needs and challenges of self-management for patients with glaucoma. Therefore, in this study, we conducted an in-depth investigation into the self-management challenges and support needs of patients with primary glaucoma, providing a basis for nursing staff to implement self-management support. Method: The phenomenological method and semistructured interviews were used in this study. A total of 20 patients with primary glaucoma were recruited between June and December 2022. Colaizzi’s analysis method was used to analyse the interview data. Results: Challenges for patients include becoming an expert in glaucoma, managing negative emotions, adapting to daily life changes and resuming social activities. To address these challenges, four themes of patient self-management support needs were identified: (1) health information support, (2) social support, (3) psychological support, and (4) daily living support. Conclusion: Patients with primary glaucoma experience varying degrees of challenge in dealing with medical, emotional, and social aspects. Comprehending the support needs of patients, healthcare professionals should deliver targeted, personalized and comprehensive self-management interventions to enhance their capacity of patients to perform self-management and improve their quality of life.

Previous studies have demonstrated that ATP citrate lyase (ACLY) plays an important role in the development of many cancers. Our current study aims to assess the effects of functional single nucleotide polymorphisms (SNPs) in ACLY gene on recurrence and survival of colorectal cancer (CRC) patients. A total of 697 resected Chinese CRC patients were included in this study. Two functional single nucleotide polymorphisms in ACLY gene were examined using the Sequenom iPLEX genotyping system. Multivariate Cox proportional hazards model and Kaplan-Meier curve were used for the prognosis analysis. Multivariate Cox regression analysis showed that there was no significant association between SNPs in ACLY gene and the prognosis of total patient cohort. However, in patients with stage III + IV diseases, the two functional SNPs (rs2304497 and rs9912300) exhibited a significant association with the risks of death (HR = 0.47, 95% CI = 0.24–0.90 and HR = 0.59, 95% CI = 0.37–0.92, respectively) and recurrence (HR = 0.46, 95% CI = 0.24–0.86 and HR = 0.54, CI = 0.35–0.83, respectively). Kaplan-Meier analysis indicated that those CRC patients carrying heterozygous (WV) or homozygous variant (VV) genotypes in rs2304497 and rs9912300 had significantly better overall survival (OS) and recurrence-free survival (RFS). Moreover, we observed remarkable cumulative effects of these two SNPs on overall survival and recurrence-free survival (P for trend = 0.012 and 0.003, respectively). Compared with patients carrying zero unfavorable genotype, those carrying two unfavorable genotypes had a 2.24-fold and 2.33-fold increase of death and recurrence risks, respectively. The SNPs in ACLY gene may serve as independent prognostic markers for patients with advanced stage CRC.

Over-expression of de novo lipogenesis (DNL) pathway genes is associated with the prognosis of various types of cancers. However, effects of single nucleotide polymorphisms (SNPs) in these genes on recurrence and death of hepatocellular carcinoma (HCC) patients after surgery are still unknown. A total of 492 primary HCC patients treated with surgery were included in this study. Nine SNPs in 3 genes (ACACA, FASN and ACLY) of DNL pathway were genotyped. Multivariate Cox proportional hazard regression model and Kaplan-Meier curve were used to analyze the association of SNPs with clinical outcomes. Two SNPs in ACACA gene were significantly associated with overall survival of HCC patients. Patients carrying homozygous variant genotype (VV) in rs7211875 had significantly increased risk of death, while patients carrying VV genotype in rs11871275 had significant decreased risk of death, when compared with those carrying homozygous wild-type or heterozygous genotypes. Moreover, patients carrying VV genotype in rs11871275 had decreased recurrence risk, while patients carrying variant genotype in rs4485435 of FASN gene had increased recurrence risk. Further cumulative effect analysis showed significant dose-dependent effects of unfavorable SNPs on both death and recurrence. SNPs in DNL genes may serve as independent prognostic markers for HCC patients after surgery.