Mass cytometry-based peripheral blood analysis as a novel tool for early detection of solid tumours: a multicentre study.

OBJECTIVE: Early detection of a tumour remains an unmet medical need, and approaches with high sensitivity and specificity are urgently required. Mass cytometry time-of-flight (CyTOF) is a powerful technique to profile immune cells and could be applied to tumour detection. We attempted to establish diagnostic models for hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC). DESIGN: We performed CyTOF analysis for 2348 participants from 15 centres, including 1131 participants with hepatic diseases, 584 participants with pancreatic diseases and 633 healthy volunteers. Diagnostic models were constructed through random forest algorithm and validated in subgroups. RESULTS: We determined the disturbance of systemic immunity caused by HCC and PDAC, and calculated a peripheral blood immune score (PBIScore) based on the constructed model. The PBIScore exhibited good performance in detecting HCC and PDAC, with both sensitivity and specificity being around 80% in the validation cohorts. We further established an integrated PBIScore (iPBIScore) by combining PBIScore and alpha-fetoprotein or carbohydrate antigen 19-9. The iPBIScore for HCC had an area under the curve (AUC) of 0.99, 0.97 and 0.96 in training, internal validation and external validation cohorts, respectively. Similarly, the iPBIScore for PDAC showed an AUC of 0.99, 0.98 and 0.97 in the training, internal validation and external validation cohorts, respectively. In early-stage and tumour-marker-negative patients, our iPBIScore-based models also showed an AUC of 0.95-0.96 and 0.81-0.92, respectively. CONCLUSION: Our study proved that the alterations of peripheral immune cell subsets could assist tumour detection, and provide a ready-to-use detection model for HCC and PDAC.

Effects of oral tauroursodeoxycholic acid and/or intestinal probiotics on serum biochemical indexes and bile composition in patients with cholecystolithiasis.

Background: In recent years, gallstones have become a major condition affecting people's health. Cholecystectomy remains an effective treatment method, but it has large risk factors. It is well known that the hepatoenteric axis plays a key role in gallstone formation, and it is gradually becoming a research focus. Cholesterol homeostasis can be regulated by the liver and intestinal tract in our bodies, and intestinal flora can regulate the digestion and absorption of cholesterol. These two factors are closely related to the formation of gallstones. Aim: To investigate the effects of tauroursodeoxycholic acid (TUDCA) and/or intestinal probiotics on serum biochemical indexes and bile composition in patients with cholecystolithiasis. Methods: For this study, 96 patients with cholecystolithiasis were recruited at our hospital. The patients were randomly divided into four groups according to a random number table: group Ⅰ (TUDCA, 24 cases), group Ⅱ (intestinal probiotics, 24 cases), group Ⅲ (TUDCA and intestinal probiotics, 24 cases) and group Ⅳ (control group, 24 cases). All patients underwent laparoscopic gallbladder-preserving lithotomy or laparoscopic cholecystectomy. Bile samples were identified and extracted during the operation. Results: The results revealed that the levels of serum total bile acid (TBA), serum total cholesterol (TCHOL) and serum triglyceride in groups I, II and III before and after the intervention were statistically significant (p < 0.05). There were significant differences in serum low-density lipoprotein cholesterol (LDL-C) between groups I and II before and after the intervention (p < 0.05), but the serum LDL-C level in group Ⅲ before and after the intervention was similar (p > 0.05). Regarding bile, TBA levels demonstrated no significant difference between groups I and III (p > 0.05), and the differences between the other two groups were statistically significant (p < 0.05). No significant difference was identified in phospholipid and TCHOL levels between groups I and Ⅲ (p > 0.05), and the differences between the other two groups were statistically significant (p < 0.05). There were significant differences in the levels of free Ca2+, pH value and glycoprotein in bile among the four groups (p < 0.05). The levels of cholic acid, chenodeoxycholic acid and deoxycholic acid in bile were significantly different among the four groups (p < 0.05). The level of lithocholic acid (LCA) in groups Ⅱ and Ⅲ was similar, as was the level of LCA in groups I and ⅠV, but the difference in level between the other two groups was statistically significant (p < 0.05). Conclusion: The combination of TUDCA and intestinal probiotics did not enhance the effect of either treatment. The use of intestinal probiotics alone can maximise the reverse development of bile composition in patients with cholecystolithiasis compared with TUDCA alone and a combination of TUDCA and intestinal probiotics, thereby reducing gallstone formation.