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Prognostic biomarkers for the pancreatic neuroendocrine tumors are needed. Proteomic study on insulinoma has been rarely reported. We identified the differential expression of proteins between insulinoma and their paired tissues by proteomic analysis, and evaluated the prognostic significance of specific proteins in pancreatic neuroendocrine tumors including insulinoma. The differential expression of select proteins was validated in more than 300 tumors using immunohistochemical staining and western blot. Methylation of UCH-L1 promoter in tumors was examined by methylation specific PCR and validated by sequencing. The concurrent expression of UCH-L1 and α-internexin was correlated with the prognosis in 2 independent collectives of patients with tumors. Sixty-two and 219 proteins were significantly down-regulated and up-regulated in insulinomas, respectively. Demethylation of UCH-L1 promoter was associated with UCH-L1 expression in tumors (p = 0.002). The concurrent expression of UCH-L1 and α-internexin in pancreatic neuroendocrine tumors was significantly associated with better overall survival and disease-free survival in the combination of both cohorts (log rank p = 3.90 × 10−4 and p = 3.75 × 10−5, respectively) and in each of cohorts. The prognostic value of both proteins was also validated in patients with stage II and III tumors (p = 0.017 and p = 0.006, respectively). The proteins UCH-L1 and α-internexin could be independent prognostic biomarkers of pancreatic neuroendocrine tumors.

Castleman’s disease (CD) is a rare lymphoproliferative disorder with clinical features and prognostic factors that are incompletely characterized. This retrospective single-center study reviewed the largest HIV-negative CD patient cohort (n = 145) to date. By clinical classification, we identified 69 patients (47.6%) as unicentric CD (UCD) and 76 patients (52.4%) as multicentric CD (MCD). Pathological classification identified 74 patients (51.0%) with the hyaline-vascular variant, 51 patients (35.2%) with the plasma-cell variant and 20 patients (13.8%) with a mixed variant. After a median follow-up duration of 58 months (range, 1–180 months), the 1-year and 5-year survival rates were 95.1% and 91.0%, respectively. UCD patients exhibited significantly better survival (1-year and 5-year survival rates of 98.5% and 97.1%, respectively) compared with MCD patients (1-year and 5-year survival rates of 92.1% and 85.5%, respectively; p = 0.005). By univariate and multivariate Cox regression analyses, the estimated glomerular filtration rate

The use of combination drugs is considered to be a promising strategy to control complex diseases such as ischemic stroke. The detection of metabolites has been used as a versatile tool to reveal the potential mechanism of diverse diseases. In this study, the levels of 12 endogenous AAs were simultaneously determined quantitatively in the MCAO rat brain using RRLC-QQQ method. Seven AAs were chosen as the potential biomarkers, and using PLS-DA analysis, the effects of the new combination drug YQJD, which is composed of ginsenosides, berberine, and jasminoidin, on those 7 AAs were evaluated. Four AAs, glutamic acid, homocysteine, methionine, and tryptophan, which changed significantly in the YQJD-treated groups compared to the vehicle groups (P < 0.05), were identified and designated as the AAs to use to further explore the synergism of YQJD. The result of a PCA showed that the combination of these three drugs exhibits the strongest synergistic effect compared to other combination groups and that ginsenosides might play a pivotal role, especially when combined with jasminoidin. We successfully explored the synergetic mechanism of multi-component and provided a new method for evaluating the integrated effects of combination drugs in the treatment of complex diseases.