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Purpose. The purpose of this study was to develop and initially validate a nomogram model in order to predict the 3-year and 5-year survival rates of neuroendocrine tumor patients. Methods. Accordingly, 348 neuroendocrine tumor patients were enrolled as study objects, of which 244 (70%) patients were included in the training set to establish the nomogram model, while 104 (30%) patients were included in the validation set to verify the robustness of the model. First, the variables related to the survival rate were determined by univariable analysis. In addition, variables that were sufficiently significant were selected for constructing the nomogram model. Furthermore, the concordance index (C-index), receiver operating characteristic (ROC), and calibration curve analysis were used to evaluate the performance of the proposed nomogram model. The survival analysis was then used to evaluate the return to survival probability as well as the indicators of constructing the nomogram model. Results. According to the multivariable analysis, lymphatic metastasis, international normalized ratio (INR), prothrombin time (PT), tumor differentiation, and the number of tumor metastases were found to be independent predictors of survival rate. Moreover, the C-index results demonstrated that the model was robust in both the training set (0.891) and validation set (0.804). In addition, the ROC results further verified the robustness of the model either in the training set ( AUC = 0.823 ) or training set ( AUC = 0.768 ). Furthermore, the calibration curve results showed that the model can be used to predict the 3-year and 5-year survival probability of neuroendocrine tumor patients. Meaningfully, five variables were found: lymphatic metastasis ( p = 0.0095 ), international standardized ratio ( p = 0.024 ), prothrombin time ( p = 0.0036 ), tumor differentiation ( p = 0.0026 ), and the number of tumor metastases ( p = 0.00096 ), which were all significantly related to the 3-year and 5-year survival probability of neuroendocrine tumor patients. Conclusion. In summary, a nomogram model was constructed in this study based on five variables (lymphatic metastasis, international normalized ratio (INR), prothrombin time (PT), tumor differentiation, and number of tumor metastases), which was shown to predict the survival probability of patients with neuroendocrine tumors. Additionally, the proposed nomogram exhibited good ability in predicting survival probability, which may be easily adopted for clinical use.

Background. Single nucleotide polymorphism (SNP) of complement component 2 (C2) has been found to be significantly associated with hepatocellular carcinoma (HCC). However, little is known about the role and mechanism of C2 in HCC. In the present study, we aimed to explore the prognostic value of C2 and its correlation with tumor-infiltrating immune cells in HCC. Materials and Methods. mRNA expression was downloaded from TCGA (365 HCC patients and 50 healthy controls), GSE14520 (220 HCC patients and 220 adjacent normal tissues), and ICGC HCC (232 HCC patients) cohorts. Unpaired Student’s t-tests or ANOVA tests were used to evaluate differences of C2 expression. Univariate and multivariate analyses were used to analyze the prognostic value of C2. CIBERSORT was used to calculate the proportion of 22 kinds of tumor-infiltrating immune cells. Results. Significantly lower C2 expression was found at HCC compared to healthy controls, and C2 was associated with TNM stages. Higher C2 expression was significantly associated with better prognosis, and multivariate analysis showed that C2 was also an independent factor for the prognosis of HCC. Moreover, elevated CD4 T cells were found at HCC patients with higher C2 expression while the higher proportion of macrophage M0 cells was found in HCC patients with lower C2 expression. KEGG analysis showed that “cell cycle,” “AMPK signaling pathway,” and “PPAR signaling pathway” were enriched in HCC patients with higher C2 expression. Conclusion. C2 is a prognostic factor for HCC and may be used as a therapeutic target for future treatment of HCC.

We explored the difference in expression of tubulin alpha 1b (TUBA1B) between Wilms’ tumor (WT) and normal tissues (NT) from in-house patients and databases, to determine TUBA1B expression in WT and the predictive pathways of coexpressed genes. In-house RNA-sequencing data were performed with WT and NT from three patients from our institute. Other four RNA-sequencing and microarray data were also downloaded from multiple public databases. The TUBA1B expression between WT and NT was analyzed by Student’s t-test and meta-analysis. The correlation between the expression of TUBA1B and other genes in each study was analyzed. Genes with p<0.05 and r>0.5 were considered as the coexpressing genes of TUBA1B. Overlapping the coexpressed genes of the five studies, including three in-house patients (3 WT vs. 3 NT), GTEx-TARGET (126 WT vs. 51 NT), GSE2172 (18 WT vs. 3 NT), GSE11024 (27 WT vs. 12 NT), and GSE73209 (32 WT vs. 6 NT), were performed with limma and VennDiagram packages in R software. The website of WEB-based GEne SeT AnaLysis toolkit were used to analyze the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotations for the overlapped genes. The results showed that the relative expression of TUBA1B in WT tissues from in-house three patients was 280.0086, 141.7589, and 303.8292 and that in NT was 16.5836, 104.8141, and 12.79 (3 WT vs. 3 NT, p=0.0285, ROC=100%, SMD=2.74). Student’s t-test and meta-analysis in all studies revealed that the expression of TUBA1B was upregulated in WT tissues compared to that in NT (p<0.05, SMD=2.89, sROC=0.98). Finally, the research identified the expression of TUBA1B in WT tissues was significantly upregulated than that in NT. The coexpressed genes of TUBA1B were enriched in the pathway of DNA replication, mismatch repair, cell cycle, pathogenic Escherichia coli infection, and spliceosome.

Objectives. Dual-energy X-ray absorptiometry (DXA) is frequently used to measure the areal bone mineral density (aBMD) in clinical practice. However, DXA measurements are affected by the bone thickness and the body size and are unable to indicate nonosseous areas within the trabecular bone. This study aims to quantify the volumetric bone mineral density (vBMD) using computed tomography (CT) images and the two-compartment model (TCM) methods. Methods. The TCM method was proposed and validated by dipotassium phosphate (K2HPO4) phantoms and a standard forearm phantom. 28 cases with DXA scans and pelvic CT scans acquired within six months were retrospectively collected. The vBMD calculated by TCM was compared with the aBMD obtained from DXA. Results. For the K2HPO4 phantoms with vBMD ranging from 0.135 to 0.467 g/cm3, the average difference between the real and calculated vBMD was 0.009 g/cm3 and the maximum difference was 0.019 g/cm3. For the standard forearm phantom with vBMD of 0.194, 0.103, and 0.054 g/cm3, the average differences between the real and calculated vBMD were 0.017, 0.014, and 0.011 g/cm3. In the clinical CT image validation, a good linear relationship between vBMD and aBMD was observed with the Pearson correlation coefficient of 0.920 (p<0.01). Conclusions. The proposed TCM method in combination with the homemade cortical bone equivalent phantom provides accurate quantification and spatial distribution of bone mineral content.

Almost all the patients with hepatocellular carcinoma (HCC) at advanced stage experience pathological changes of chronic liver cirrhosis, which generally leads to moderate ascites. Recognition of novel biomarkers in malignant ascites could be favorable for establishing a diagnosis for the HCC patients with ascites, and even predicting prognosis, such as risk of distant metastasis. To distinguish the proteomic profiles of malignant ascites in HCC patients from those with nonmalignant liver cirrhosis, an iTRAQ pipeline was built up to analyze the differentially distributed proteins in the malignant ascites from HCC patients (n=10) and benign ascites from hepatic decompensation (HD) controls (n=9). In total, 112 differentially distributed proteins were identified, of which 69 proteins were upregulated and 43 proteins were downregulated (ratio 1.3, respectively) in the malignant ascites. Moreover, 19 upregulated proteins (including keratin 1 protein and rheumatoid factor RF-IP20, ratio>1.5) and 8 downregulated proteins (including carbonic anhydrase 1, ratio

Background. Serum bilirubin is a potent endogenous antioxidant with anti-inflammatory properties. Several cross-sectional studies have reported that bilirubin was negatively associated with metabolic syndrome. However, in recent longitudinal studies, the relations between bilirubin and metabolic syndrome are inconsistent. Moreover, previous studies mainly focused on serum total bilirubin which is the sum of direct bilirubin and indirect bilirubin. For these reasons, the longitudinal effect of bilirubin subtypes on incident metabolic syndrome was evaluated in Chinese men. Methods. The study cohort involved 1339 Chinese men without metabolic syndrome. Metabolic syndrome was defined by the American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLBI) criteria, using BMI for the replacement of waist circumference. Results. There are 117 incident metabolic syndrome cases (8.7%) during 5 years of follow-up among 1339 metabolic syndrome-free participants at baseline. After adjusting for age, drinking, smoking, physical activity, TG, and LDL-C, the odd ratios (ORs) and 95% confidence intervals (CIs) for MetS incidence in the second, third, and fourth quartiles versus the first quartile of DBil concentration were 1.00 (0.61–1.63), 0.57 (0.32–1.02), and 0.51 (0.28–0.92) (Ptrend=0.031), respectively. Conclusions. Our findings support the negative association between direct bilirubin and incident metabolic syndrome in healthy Chinese men over 5-year period.

Primordial follicle formation represents a critical phase of the initiation of embryonic reproductive organ development, while the primordial follicle transition into primary follicle determines whether oestrus or ovulation will occur in female animals. To identify molecular mechanism of new proteins which are involved in ovarian development, we employed 2D-DIGE to compare the protein expression profiles of primordial follicles and primary follicles of fetal ovaries in pigs. Fetal ovaries were collected at distinct time-points of the gestation cycle (g55 and g90). The identified proteins at the g55 time-point are mainly involved in the development of anatomical structures [reticulocalbin-1 (RCN1), reticulocalbin-3 (RCN3)], cell differentiation (actin), and stress response [heterogeneous nuclear ribonucleoprotein K (HNRNPK)]. Meanwhile, at the g90 stage, the isolated proteins with altered expression levels were mainly associated with cell proliferation [major vault protein (MVP)] and stress response [heat shock-related 70 kDa protein 2 (HSPA2)]. In conclusion, our work revealed that primordial follicle formation is regulated by RCN1, RCN3, actin, and HNRNPK, while the primordial follicle transformation to primary follicle is regulated by MVP and HSPA2. Therefore, our results provide further information for the prospective understanding of the molecular mechanism(s) involved in the regulation of the ovarian follicle development.

Phyllanthus niruri L., a well-known medicinal plant, has been used as a folk antitumor remedy in the worldwide scale. However, the antitumor components in P. niruri have not been reported. In order to verify the antitumor components of P. niruri and the plants which have the high content of these components, we isolated the antitumor components with bioguided fraction and isolation, by different chromatographic methods from the ethyl acetate fraction of P. niruri., and identified them as ethyl brevifolincarboxylate and corilagin by 1H-NMR, 13C-NMR, 2D-NMR, and mass spectrometric analyses. Cell cytotoxicity assays showed that corilagin has broad-spectrum antitumor activity, a better antitumor potential, and lower toxicity in normal cells. Besides, the coefficient of drug interaction (CDI) of 10 μM corilagin and 20 μM cDDP reached up to 0.77, which means corilagin can promote the antitumor activity of cDDP. Furthermore, by the extensive screening among 10 species of plants reported to contain corilagin, we found that Dimocarpus longan Lour. has the maximum content of corilagin. In conclusion, corilagin is the major active antitumor composition in P. niruri. L. on HCC cells and has high content in D. longan.

Background. The impact of the various components of metabolic syndrome (MetS) on chronic kidney disease has been conflicting. We aim to investigate the association between MetS and microalbuminuria and identify the major contributing components of MetS that result in microalbuminuria in the Chinese aged population. Methods. A total of 674 adults aged 55–98 years (males: 266; mean age: 66.5±7.5 years) were studied. MetS was defined by the 2004 Chinese Diabetes Society criteria and microalbuminuria by urine albumin-creatinine ratio (UACR) ≥3 mg/mmoL. Results. The prevalence of microalbuminuria was gradually increased with increasing number of MetS components (P<0.05). In multivariate regression, after adjusting for age and sex, MetS was the strongest correlate of microalbuminuria (OR = 1.781, 95% CI = 1.226–2.587; P<0.05) followed by the fasting plasma glucose (FPG) (OR = 1.217, 95% CI = 1.044–1.092; P<0.05), systolic blood pressure (SBP) (OR = 1.011, 95% CI = 1.107–1.338; P<0.05), and high-density lipoprotein cholesterol (HDL-C) (OR = 0.576, 95% CI = 0.348–0.953; P<0.05). Conclusions. MetS is independently associated with microalbuminuria in the Chinese aged population. Elevated FPG is the most predominant component of metabolic syndrome associated with microalbuminuria followed by elevated SBP and reduced HDL-C.

Background. Aberrant expression of high mobility group box-1 protein (HMGB1) contributes to the progression of various inflammatory diseases. This meta-analysis focused on the clinical significance of serum HMGB1 levels in pancreatitis patients, with the goal of building a novel diagnostic score model.Method. We conducted a meta-analysis by searching in the PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, China BioMedicine (CBM), and China National Knowledge Infrastructure (CNKI) databases without any language restrictions. Studies were pooled and standard mean difference (SMD) and its corresponding 95% confidence intervals (95% CIs) were calculated. Version 12.0 STATA software was used for statistical analysis.Results. We performed a final analysis of 841 subjects from 12 clinical case-control studies. The meta-analysis results showed a positive association between serum HMGB1 levels and the progression of pancreatitis. In the subgroup analysis by country, high serum level of HMGB1 may be related to pancreatitis progression in China, Korea, Hungary, and Japan populations (allP<0.05).Conclusion. The present meta-analysis indicated that serum HMGB1 level was statistically elevated in patients with pancreatitis, and thus serum levels of HMGB1 could be determined to be a useful biomarker for pancreatitis patients.