Tumor recurrence in hepatocellular carcinoma (HCC) patients after radiofrequency ablation (RFA) remains common; some studies have reported that insufficient ablative margin after RFA might contribute to HCC recurrence. The aim of this study was to investigate whether insufficient ablative safety margins determined by early computed tomography (CT) predicts HCC recurrence after RFA. This retrospective study recruited patients with a single HCC lesion after RFA in our department between May 2013 and March 2014. Early follow-up CT was performed within 7 days after RFA. An adequate ablative margin assessed by follow-up CT was defined as (maximum post-RFA CT radius)³/(maximum pre-RFA CT radius + 5 mm)³> 1. All patients in whom complete ablation was achieved underwent a CT scan every 3 months for early detection of HCC recurrence. In total, 72 patients (48 male, mean age 69.4 years) were analyzed. Of these, eight patients had local tumor progression, four had intra-hepatic distant recurrence, and two had extra-hepatic metastasis. Insufficient ablative margin, defined as an ablative volume with a safety margin of less than 5 mm, was an important predictor of local tumor progression (LTP) (p = 0.015) and overall recurrence (p = 0.012). The sensitivity, specificity, and positive and negative predictive values of an insufficient ablative margin for predicting LTP and overall recurrence were 36.4%, 97.2%, 50.0%, and 87.9%, and 46.2%, 89.7%, 42.9%, and 87.9%, respectively. An ablative volume with an ablative margin of less than 5 mm is associated with higher rates of both LTP and overall recurrence in HCC after RFA.

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Intracerebral hemorrhage (ICH) is a subtype of stroke that is followed by primary and secondary brain injury. As a result of the injury, cell metabolism is disrupted and a series of stress responses are activated, such as endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), leading to the re-establishment of cell homeostasis or cell death. As an important mechanism of cell homeostasis, autophagy has been widely studied, and the associations between autophagy, ER stress, and the UPR have also been demonstrated. Whether these mechanisms are beneficial or detrimental remains a matter of controversy, but there is no doubt as to their vital functions. An understanding of the mechanisms of injury and recovery after ICH is crucial to develop therapeutic strategies. In this review, we summarize the related studies and highlight the roles of autophagy, ER stress, and the UPR in disease, especially in ICH. We also provide an overview of therapeutic approaches that target autophagy, and we discuss the prospects for modulating autophagy, ER stress, and UPR mechanisms in ICH therapy.

BaCKgRoUND aND aIMS: PreS mutants of HBV have been reported to be associated with HCC. We conducted a longitudinal study of the role of HBV preS mutations in the development of HCC, particularly in patients with chronic hepatitis B (CHB) having low HBV DNA or alanine aminotransferase (ALT) levels, and investigated the effects of secretion-defective preS2 deletion mutant (preS2ΔMT) on hepatocyte damage in vitro and liver fibrosis in vivo.appRoaCH aND ReSUltS: Association of preS mutations with HCC in 343 patients with CHB was evaluated by a retrospective case-control follow-up study. Effects of preS2ΔMT on HBsAg retention, endoplasmic reticulum (ER) stress, calcium accumulation, mitochondrial dysfunction, and liver fibrosis were examined. Multivariate analysis revealed a significant association of preS mutations with HCC (HR, 3.210; 95% CI, 1.072-9.613; P = 0.037) including cases with low HBV DNA or ALT levels (HR, 2.790; 95% CI, 1.133-6.873; P = 0.026). Antiviral therapy reduced HCC risk, including cases with preS mutations. PreS2ΔMT expression promoted HBsAg retention in the ER and unfolded protein response (UPR). Transmission electron microscopic examination, MitoTracker staining, real-time ATP assay, and calcium staining of preS2ΔMT-expressing cells revealed aberrant ER and mitochondrial ultrastructure, reduction of mitochondrial membrane potential and ATP production, and calcium overload. Serum HBV secretion levels were ~100fold lower in preS2ΔMT-infected humanized Fah-/-/ Rag2-/-/ Il2rg-/-triple knockout mice than in wild-type HBV-infected mice. PreS2ΔMT-infected mice displayed up-regulation of UPR and caspase-3 and enhanced liver fibrosis.

Alzheimer's disease is a neurodegenerative disorder associated with the deposition of the peptide amyloid-beta (Aβ) in senile plaques and cerebral vasculature. The neurotoxic mechanisms of this condition have been linked to oxidative-stress-induced apoptosis leading to widespread neuronal loss. Herein, we demonstrate the neuroprotective effects of a ketone body D-β-hydroxybutyrate (β-HB) in neural cell lines and an animal model induced by injecting Aβ into the hippocampus. Using histological examination and the TUNEL assay, we show that administration of exogenous β-HB effectively prevents Aβ deposition and neuron apoptosis in this rat model. β-HB pretreatment also relieves the oxidative stress in Aβ-induced PC-12 cells, as shown by decreased intracellular reactive oxygen species and Ca(2+) levels, activated Nrf2 and recovered superoxide dismutase and catalase activities. Consequently, the apoptotic pathway is also inhibited in these cells, with decreased levels of p53, caspase-12, caspase-9, caspase-3; a decreased Bax/Bcl-2 ratio; and decreased cytochrome c release. Taken together, our study provides a molecular basis for the neuroprotective effects of β-HB in line with the suppression of oxidative stress and the inhibition of apoptotic protein activation.

Periodontitis induced by bacteria especially Porphyromonas gingivalis (P. gingivalis) is the most prevalent microbial disease worldwide and is a significant risk factor for systemic diseases such as rheumatoid arthritis (RA). RA and periodontitis share similar clinical and pathologic features. Moreover, the prevalence of RA is much higher in patients with periodontitis than in those without periodontitis. To explore the immunologic mechanism of periodontitis involved in RA, we established a mouse model of periodontitis and then induced RA. According to the results of paw thickness, arthritis clinical score, arthritis incidence, microscopic lesion using H&E staining, and micro‐CT analysis, periodontitis induced by P. gingivalis promoted the occurrence and development of collagen‐induced arthritis (CIA) in mice. Furthermore, periodontitis enhanced the frequency of CD19+ B cells, Th17, Treg, gMDSCs, and mMDSCs, whereas down‐regulated IL‐10 producing regulatory B cells (B10) in CIA mice preinduced for periodontitis with P. gingivalis. In vitro stimulation with splenic cells revealed that P. gingivalis directly enhanced differentiation of Th17, Treg, and mMDSCs but inhibited the process of B cell differentiation into B10 cells. Considering that adoptive transfer of B10 cells prevent RA development, our study, although preliminary, suggests that down‐regulation of B10 cells may be the key mechanism that periodontitis promotes RA as the other main immune suppressive cells such as Treg and MDSCs are up‐regulated other than down‐regulated in group of P. gingivalis plus CIA.

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