Circulating miRNAs (microRNAs) are emerging as promising biomarkers for several pathological conditions, and the aim of this study was to investigate the feasibility of using serum miRNAs as biomarkers for liver pathologies. Real-time qPCR (quantitative PCR)-based TaqMan MicroRNA arrays were first employed to profile miRNAs in serum pools from patients with HCC (hepatocellular carcinoma) or LC (liver cirrhosis) and from healthy controls. Five miRNAs (i.e. miR-885-5p, miR-574-3p, miR-224, miR-215 and miR-146a) that were up-regulated in the HCC and LC serum pools were selected and further quantified using real-time qPCR in patients with HCC, LC, CHB (chronic hepatitis B) or GC (gastric cancer) and in normal controls. The present study revealed that more than 110 miRNA species in the serum samples and wide distribution ranges of serum miRNAs were observed. The levels of miR-885-5p were significantly higher in sera from patients with HCC, LC and CHB than in healthy controls or GC patients. miR-885-5p yielded an AUC [the area under the ROC (receiver operating characteristic) curve] of 0.904 [95% CI (confidence interval), 0.837–0.951, P<0.0001) with 90.53% sensitivity and 79.17% specificity in discriminating liver pathologies from healthy controls, using a cut off value of 1.06 (normalized). No correlations between increased miR-885-5p and liver function parameters [AFP (α-fetoprotein), ALT (alanine aminotransferase), AST (aspartate aminotransferase) and GGT (γ-glutamyl transpeptidase)] were observed in patients with liver pathologies. In summary, miR-885-5p is significantly elevated in the sera of patients with liver pathologies, and our data suggest that serum miRNAs could serve as novel complementary biomarkers for the detection and assessment of liver pathologies.

Exosomal microRNAs have recently been studied as the potential diagnostic marker for various malignancies, including hepatocellular carcinoma (HCC). The aim of this study was to investigate serum exosomal microRNA profiles as HCC diagnostic marker. Transmission electron microscopy and Western blot were used to identify serum exosomes. Deep sequencing was performed to screen differentially expressed microRNAs between HCC (n = 5) and liver cirrhosis (LC, n = 5) groups. Three upregulated and two downregulated microRNAs were selected for qPCR analysis. The levels of selected microRNAs were normalized to Caenorhabditis elegans miR‐39 microRNA mimics. Serum exosomal level of miR‐122, miR‐148a, and miR‐1246 was further analyzed and significantly higher in HCC than LC and normal control (NC) groups (P < 0.001), but not different from chronic hepatitis group (P > 0.05). The receiver operating characteristic curve was used to evaluate the diagnostic performance of candidate microRNAs. Area under the curve (AUC) of miR‐148a was 0.891 [95% confidence interval (CI), 0.809–0.947] in discriminating HCC from LC, remarkably higher than alpha‐fetoprotein (AFP) (AUC: 0.712, 95% CI: 0.607–0.803). Binary logistic regression was adopted to establish the diagnostic model for discriminating HCC from LC. And the combination of miR‐122, miR‐148a, and AFP increased the AUC to 0.931 (95% CI, 0.857–0.973), which can also be applied for distinguishing early HCC from LC. miR‐122 was the best for differentiating HCC from NC (AUC: 0.990, 95% CI, 0.945–1.000). These data suggest that serum exosomal microRNAs signature or their combination with traditional biomarker may be used as a suitable peripheral screening tool for HCC.

We have investigated the changing rule of serum form of GP73 (sGP73) in different hepato‐pathologic processes and identified the sGP73 role in inflammation, fibrosis and carcinogenesis since sGP73 has been regarded as a candidate tumor marker. Quantitative enzyme‐linked immunosorbent assay detected sGP73 in 535 subjects with hepatocellular carcinoma (HCC), liver cirrhosis (LC), hepatitis, focal nodular hyperplasia (FNH), angioma, intra‐hepatic cholangio‐carcinoma (ICC) and metastatic cancer from adenocarcinomas (MC). Median sGP73 in LC was higher than in HCC and hepatitis (p = 0.001), and sGP73 in all three groups were higher than those in healthy individuals (p < 0.001); sGP73 in LC patients with Child‐Pugh class A was lower than in class B and C (p = 0.001), no significant difference was found between early and advanced HCC groups (110.4 μg/L vs. 102.8 μg/L). AFP/GP73 had a sensitivity of 75.8% and specificity of 79.7% with an area under the receiver operating curve (AUROC) of 0.844 vs. 0.812 for AFP (p = 0.055) with a sensitivity of 95.2% and specificity of 47.1%; in detecting early HCC, AUROC of AFP/GP73 was 0. 804 vs. 0.766 for AFP (p = 0.086). sGP73 correlated with AST, AST/ALT, ALB, A/G and ALP in LC. The positive rate of sGP73 in angioma, FNH, ICC, and MC was 0, 50, 63.3, 53.3%, respectively; AFP/GP73 was 0.796 with the sensitivity of 81.4% and specificity of 70.0% when differentiating MC from AFP‐negative HCC. Increased sGP73 is related to hepatic impairment and chronic fibrosis, and when combined with AFP could improve the differential diagnosis of hepatic diseases.

Proton pump inhibitors (PPIs) are commonly used to lessen symptoms in patients with gastroesophageal reflux disease (GERD). However, the effects of PPI therapy on the gastrointestinal microbiota in GERD patients remain unclear. We examined the association between the PPI usage and the microbiota present in gastric mucosal and fecal samples from GERD patients and healthy controls (HCs) using 16S rRNA gene sequencing. GERD patients taking PPIs were further divided into short-term and long-term PPI user groups. We showed that PPI administration lowered the relative bacterial diversity of the gastric microbiota in GERD patients. Compared to the non-PPI-user and HC groups, higher abundances of Planococcaceae, Oxalobacteraceae, and Sphingomonadaceae were found in the gastric microbiota from the PPI-user group. In addition, the Methylophilus genus was more highly abundant in the long-term PPI user group than in the short-term PPI-user group. Despite the absence of differences in alpha diversity, there were significant differences in the fecal bacterial composition of between GERD patients taking PPIs and those not taking PPIs. There was a higher abundance of Streptococcaceae, Veillonellaceae, Acidaminococcaceae, Micrococcaceae, and Flavobacteriaceae present in the fecal microbiota from the PPI-user group than those from the non-PPI-user and HC groups. Additionally, a significantly higher abundance of Ruminococcus was found in GERD patients on long-term PPI medication than that on short-term PPI medication. Our study indicates that PPI administration in patients with GERD has a significant effect on the abundance and structure of the gastric mucosal microbiota but only on the composition of the fecal microbiota.

Early detection of pancreatic cancer is promising for improving clinical outcome; however, no effective biomarker has yet been identified. Here, we detected 61 clinical serum parameters in 200 healthy controls (Ctrls), 163 pancreatic ductal adenocarcinoma (PDAC) patients and 109 benign pancreatitis patients (Benign) in the training group. A metropolis algorithm with Monte Carlo simulation was used for identifying parameter panels. Sera from 183 Ctrl, 129 PDAC and 95 Benign individuals were used for cross‐validation. Samples from 77 breast, 72 cervical, 101 colorectal, 138 gastric, 108 prostate and 132 lung cancer patients were collected for evaluating cancer selectivity. A panel consisting of carbohydrate antigen (CA)19‐9, albumin (ALB), C‐reactive protein (CRP) and interleukin (IL)−8 had the highest diagnostic value for discriminating between PDAC and Ctrl. The sensitivity (SN) was 99.39% for all‐stage, 96.10% for early‐stage and 98.80% for advanced‐stage PDAC at 90% specificity (SP). In the validation group, the sensitivities were 93.80, 93.10 and 94.40%, respectively, at 90% SP. This panel also identified 80.52% of the breast cancer, 66.67% cervical cancer, 86.14% colorectal cancer, 89.86% gastric cancer, 71.30% prostate cancer and 93.85% lung cancer samples as non‐PDAC. The panel consisting of CA19‐9, carbon dioxide, CRP and IL‐6 panel had the highest diagnostic value for discriminating between PDAC and Benign. The SN was 74.23% for all‐stage, 75.30% for early‐stage and 74.40% for advanced‐stage PDAC at 90% SP. In the validation group, the sensitivities were 72.10, 76.10 and 67.20%, respectively, at 90% SP. Our parameter panels may aid in the early detection of PDAC to improve clinical outcome.

It is indicated that non-HDL cholesterol and lipid ratios, including total/HDL cholesterol and LDL/HDL cholesterol ratios, are risk indicators with greater predictive value for coronary atherosclerotic progression or regression compared with conventional lipid profile. However, there have been few reports about the correlation between serum lipid profile with carotid intima-media thickness (IMT) and plaque in Chinese general people. We examined 402 subjects without apparent diseases in a cross-sectional study (mean age 50.16 years; 36.07% female). Demographics, anthropometrics, and laboratory data were collected. The presence of carotid plaque and intima-media thickness were evaluated by ultrasonography. Univariate correlations showed carotid IMT was correlated with LDL-C (r = 0.137, p = 0.009), non-LDL-C levels (r = 0.140, p = 0.008) and LDL-C/HDL-C ratio (r = 0.169, p = 0.001). After adjustment for potential covariates, LDL-C/HDL-C ratio (β = 0.132, p < 0.001) were independent variables that interacted on carotid IMT. Other risk factors including age and systolic blood pressure were independently associated with carotid IMT. LDL-C levels, non-HDL-C levels, TC/HDL-C and LDL-C/HDL-C ratios were significantly higher, but HDL-C levels were significantly lower in subjects with carotid plaque than those without it. The subsequent multiple logistic regression analysis showed that LDL-C (OR; 1.325, 95% CI; 1.046-1.821, p = 0.033) and HDL-C levels (OR; 0.093, 95% CI; 0.038-0.227, p < 0.001) were significantly associated with the presence of carotid plaque after adjustment of age. Furthermore, LDL-C combined with HDL-C levels showed the highest area under the curve (0.788, 95% CI; 0.740–0.837, p < 0.001). Serum LDL-C/HDL-C ratio represents as an independent index associated with increased carotid IMT and LDL-C combined with HDL-C levels may be useful markers for predicting the presence of carotid plaque in the Chinese general population.