Background Optimal therapeutic strategies for hepatocellular carcinoma (HCC) patients are still challenging due to the high recurrence rate after surgical resection and chemotherapy resistance. Growing evidence shows that genetic and epigenetic alterations are involved in HCC progression and resistance to therapy, however the molecular mechanisms underlying resistance to therapy have not been fully understood. Methods Expression of SIRT7 in 17 paired paraffin-embedded HCC tissues and adjacent nontumoral liver tissues was examined by immunohistochemistry and Western blot. The mRNA expression of SIRT7 in 20 paired frozen HCC tissues and adjacent nontumoral liver tissues was analyzed by quantitative RT-PCR. The biologic consequences of overexpression and knockdown of SIRT7 in HCC therapy sensitivity were studied in vitro and in vivo. Interaction between SIRT7 and p53 were studied in HCC cell lines. Results SIRT7 expression was frequently upregulated in clinical HCC samples, and its expression was highly associated with TACE-resistance and poor survival (P = 0.008.) Depletion of SIRT7 from multiple liver cancer cell lines significantly increased doxorubicin toxicity while overexpression of SIRT7 largely abolished doxorubicin induced apoptosis. At the molecular level, we observed that SIRT7 interacts with and induces deacetylation of p53 at lysines 320 and 373. Deacetylated p53 showed significantly less affinity for the NOXA promoter and its transcription. In mouse xenografts, SIRT7 suppression increased doxorubicin induced p53 activation, inhibited tumor growth and induced apoptosis. Conclusion The newly identified SIRT7-p53-NOXA axis partially illustrates the molecular mechanism of HCC resistance to therapy and represents a novel potential therapeutic target for HCC treatment. Electronic supplementary material The online version of this article (10.1186/s13046-019-1246-4) contains supplementary material, which is available to authorized users.

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In this retrospective study of 164 patients with alcohol‐associated hepatitis, we find that the mean absolute monocyte count is 0.95 thousand cells/L, which is significantly higher than the upper limit of normal (0.80 thousand cells/μL) (P < 0.0001). Monocyte count is correlated with disease severity as measured by MELD score (R = 0.400, P < 0.0001) and Maddrey discriminant function (R = 0.330, P < 0.0001).

The management of pain and sedation during burn dressing change is challenging. Previous reviews and studies have identified wide variability in such practices in hospitalized burn patients. This survey-based study aimed to determine the most commonly utilized sedation and analgesia practices in adult burn patients treated in the outpatient setting. The goal was to identify opportunities for improvement and to assist burn centers in optimizing sedation procedures. A 23-question survey was sent to members of the American Burn Association. Nonpharmacological interventions including music, television, games, and virtual reality were used by 68% of survey respondents. Eighty-one percent reported premedicating with oral opioids, 32% with intravenous opioids, and 45% with anxiolytics. Fifty-nine percentage of respondents indicated that the initial medication regimen for outpatient dressing changes consisted of the patient's existing oral pain medications. Forty-three percent indicated that there were no additional options if this regimen provided inadequate analgesia. Fifty-six percentage of respondents felt that pain during dressing change was adequately controlled 75% to 100% of the time, and 32% felt it was adequately controlled 50% to 75% of the time. Nitrous oxide was used by 8%. Anesthesia providers and an acute pain service are available in a minority of cases (13.7% and 28%, respectively) and are rarely consulted. Procedural burn pain remains significantly undertreated in the outpatient setting and the approach to treatment is variable among burn centers in the United States. Such variation likely represents an opportunity for identifying and implementing optimal practices and developing guidelines for burn pain management in the outpatient setting.

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