Problems related to the central nervous system have a major impact on survival and quality of life. The aim of this retrospective study was to evaluate the incidence of neurological complications after liver transplantation (LT), including both cadaveric and living donor liver transplantation. Between April 2001 and March 2004 174 patients (120 cadaveric liver transplantations, 54 living donor transplantations) were admitted to our intensive care after liver transplantation. Of the transplanted patients 24.7% developed neurological complications. These patients' stay in the intensive care (14.2 +/- 17.2 days) was much longer than that of all admitted patients (8.4 +/- 10.5 days, p < 0.05). The most common neurological complications were encephalopathy (72.1%) and seizures (11.6 %). The incidence of neurological complications in living donor liver transplanted patients was significantly lower than in cadaveric transplantation patients (20.4% vs 26.7 %). The cold ischemia time in living donor transplanted patients was significantly shorter in comparison with cadaveric transplanted patients (215 +/- 119.3 vs. 383.7 +/- 214.7). The survival rate after liver transplantation of patients with neurological complications was lower than that of patients without, but not significantly different (79.1 % vs. 82.4%, p > 0.05). The incidence of neurological symptoms was found to be similar between the patients treated with cyclosporine (25%) and tacrolimus (23.8 %) in this study. In conclusion, there was a high incidence of neurological complications after LT, prolonging the patients' stay in intensive care significantly. The major neurological manifestation in our patients was encephalopathy followed by seizures. Living donor liver transplantation was associated with a significantly lower incidence of neurological complications compared with patients who had received a cadaveric graft. This might be due to the good quality of the organ and the much shorter cold ischemia time of the graft when the donor was alive.

Golgi phosphoprotein 2 (GOLPH2) is a resident Golgi type-II membrane protein upregulated in liver disease. Given that GOLPH2 traffics through endosomes and can be secreted into the circulation, it is a promising serum marker for liver diseases. The structure of GOLPH2 and the functions of its different protein domains are not known. In the current study, we investigated the structural determinants for Golgi localization using a panel of GOLPH2 truncation mutants. The Golgi localization of GOLPH2 was not affected by the deletion of the C-terminal part of the protein. A truncated mutant containing the N-terminal portion (the cytoplasmic tail and transmembrane domain (TMD)) localized to the Golgi. Sequential deletion analysis of the N-terminal indicated that the TMD with a positively charged residue in the cytoplasmic N-terminal tail were sufficient to support Golgi localization. We also showed that both endogenous and secreted GOLPH2 exist as a disulfide-bonded dimer, and the coiled-coil domain was sufficient for dimerization. This structural knowledge is important for the understanding the pathogenic role of GOLPH2 in liver diseases, and the development of GOLPH2-based hepatocellular cancer diagnostic methods.

Background: Golgi protein-73 (GP73) is a newly identified candidate serum marker for liver diseases. The utility of this biomarker remains limited, largely due to the lack of quantitative information. The aims of this study were to quantify serum GP73 (sGP73) in healthy individuals and in patients with liver diseases, and to validate sGP73 as a biomarker for early diagnosis of liver disease. Methods: Recombinant GP73 was used to generate monoclonal (mAb) and polyclonal antibodies ( pAb). Using these antibodies in a quantitative enzyme-linked immunosorbent assay, GP73 was measured in serum from 263 patients with various forms of liver and other diseases. Results: The median sGP73 in patients with liver disease was significantly higher (P , 0.001) than in healthy individuals and in patients with other diseases. When sGP73 was used to detect liver disease, it had a sensitivity of 82% and a specificity of 80% at the optimal cut-off value of 85.5 mg/L. The area under the receiver-operating characteristic curve was 0.9. Conclusion: sGP73 concentration in patients with liver disease was three-fold higher than in healthy individuals. However, sGP73 concentrations did not differ significantly between patients from each liver disease group. Furthermore, sGP73 was not significantly elevated in patients with diseases other than liver disease compared with healthy individuals. These results suggest that sGP73 may be used as a serum marker for the diagnosis of liver disease.

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Tumor angiogenesis, growth and metastasis are three closely related processes. We therefore explored the effects of (-)-oleocanthal (OC) on the three processes in melanoma and investigated underlying mechanisms. In vitro, OC suppressed proliferation, migration, invasion and induced apoptosis in melanoma cells. In addition, OC inhibited proliferation, migration, invasion and tube formation in human umbilical vascular endothelial cells. In vivo, it exhibited potent activity in suppressing tumor growth in a subcutaneous xenograft model. Furthermore, OC suppressed proliferation and angiogenesis as measured by immunohistochemical staining of Ki-67 and CD31. In addition, OC was found to inhibit metastasis of melanoma in a lung metastasis model. Mechanistically, OC significantly suppressed signal transducer and activator of transcription 3 (STAT3) phosphorylation, decreased STAT3 nuclear localization and inhibited STAT3 transcriptional activity. OC also downregulated STAT3 target genes, including Mcl-1, Bcl-xL, MMP-2, MMP-9, VEGF, which are involved in apoptosis, invasion and angiogenesis of melanoma. These results support further investigation of OC as a potential anti-melanoma drug.

To identify the risk factors of mortality for the coronavirus disease 19 (COVID-19) patients admitted to intensive care units (ICUs) through a retrospective analysis. The demographic, clinical, laboratory, and chest imaging data of patients admitted to the ICU of Huoshenshan Hospital from February 10 to April 10, 2020 were retrospectively analyzed. Student's t-test and Chi-square test were used to compare the continuous and categorical variables, respectively. The logistic regression model was employed to ascertain the risk factors of mortality. This retrospective study involved 123 patients, including 64 dead and 59 survivors. Among them, 57 people were tested for interleukin-6 (IL-6) (20 died and 37 survived). In all included patients, the oxygenation index (PaO2/FiO2) was identified as an independent risk factor (odd ratio [OR] = 0.96, 95% confidence interval [CI]: 0.928–0.994, p = 0.021). The area under the curve (AUC) was 0.895 (95% CI: 0.826–0.943, p < 0.0001). Among the patients tested for IL-6, the PaO2/FiO2 (OR = 0.955, 95%CI: 0.915–0.996, p = 0.032) and IL-6 (OR = 1.013, 95%CI: 1.001–1.025, p = 0.028) were identified as independent risk factors. The AUC was 0.9 (95% CI: 0.791–0.964, p < 0.0001) for IL-6 and 0.865 (95% CI: 0.748–0.941, p < 0.0001) for PaO2/FiO2. PaO2/FiO2 and IL-6 could potentially serve as independent risk factors for predicting death in COVID-19 patients requiring intensive care.

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