Plasma metabolomics signatures of developmental dysplasia of the hip in Tibet plateau.

BACKGROUND: Developmental dysplasia of the hip (DDH) is a common childhood health complaint, whose etiology is multifactorial. The incidence of DDH is variable and higher in Tibet plateau. Here, we collected plasma samples and studied the metabolomics signatures of DDH. METHODS: Fifty babies were enrolled: 25 with DDH and 25 age-matched non-DDH healthy controls (HC group). We collected plasma samples, laboratory parameters and conducted untargeted metabolomics profiling. RESULTS: There are many differential metabolites among patients with DDH, including 4-ß-hydroxymethyl-4-α-methyl-5-α-cholest-7-en-3-beta-ol, ß-cryptoxanthin, α-tocopherol, taurocholic acid, glycocholic acid, 2-(3,4-dihydroxybenzoyloxy)-4,6-dihydroxybenzoate, arabinosylhypoxanthine, leucyl-hydroxyproline, hypoxanthine. The main differential metabolic pathways focused on primary bile acid biosynthesis, arginine and proline metabolism, phenylalanine metabolism, histidine metabolism, purine metabolism. CONCLUSIONS: To our knowledge, this is the first report of metabolomics profile in babies with DHH. By combining the α-tocopherol and taurocholic acid, we could achieve the differential diagnosis of DDH.

Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001).

There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4-11.0) versus 8.0 months (95% CI, 6.6-9.5) (adjusted hazard ratio [HR], 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1-27.3] vs. 15.7 months [13.0-20.2]; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile.

Corrigendum: The Application of Preoperative Three-Dimensional Reconstruction Visualization Digital Technology in the Surgical Treatment of Hepatic Echinococcosis in Tibet.

[This corrects the article DOI: 10.3389/fsurg.2021.715005.].

The Application of Preoperative Three-Dimensional Reconstruction Visualization Digital Technology in the Surgical Treatment of Hepatic Echinococcosis in Tibet.

Objective: The present study aims to explore the application value of three-dimensional (3D) reconstruction technology in the preoperative evaluation of patients with complicated hepatic echinococcosis in Tibet. Methods: A total of 200 patients with complicated hepatic echinococcosis, admitted to our hospital between May 2019 and December 2020, who underwent radical hepatectomy, were enrolled in the present study. The patients were randomly divided into a preoperative computer tomography group and a preoperative 3D reconstruction group. According to the imaging results, a surgical plan was formulated. A comparison was made between the two groups of the coincidence rate of the surgical plan and intraoperative and postoperative complications. Results: The patients with hepatic echinococcosis who underwent 3D visualization reconstruction before surgery had a high compliance rate with the surgical plans and the operating time, the number of cases with blood flow blockage, the blood flow blockage time, intraoperative hemorrhage, and postoperative biliary fistulas were significantly lower. Conclusion: The application of preoperative 3D visualization reconstruction in patients with complicated hepatic echinococcosis in Tibet could effectively improve surgical safety.

Clinical significance of the reduction of UT-B expression in urothelial carcinoma of the bladder.

Urea transporter B (UT-B) is a membrane protein and plays an important role in regulating urea concentration in bladder urothelial cells. It has been reported that UT-B gene mutations were related to bladder carcinogenesis, and UT-B deletion could induce DNA damage and apoptosis in bladder urothelium. However, the functions and clinical significance of UT-B in human bladder cancer remain unknown. The most common type of bladder cancer is urothelial carcinoma (UC). We hypothesized that UT-B expression was related to bladder UC progress. In this study, UT-B was detected using immunohistochemistry in 52 paraffin-embedded specimens of bladder UC and 10 normal urothelium specimens. The results showed that UT-B protein expression in UC tumor cells was significantly lower as compared with normal urothelial cells (P = 0.021). UT-B protein expression was significantly reduced with increasing histological grade (P = 0.010). UT-B protein expression in muscle-invasive stage was significantly lower than in non-muscle-invasive stage (P = 0.014). Taken together, our data suggest that the reduction or loss of UT-B expression may be related to the incidence, progression and invasiveness of bladder UC. UT-B may be a novel diagnostic or prognostic biomarker, as well as a potential therapeutic target in UC of the bladder.

FOXP3 and TLR4 protein expression are correlated in non-small cell lung cancer: implications for tumor progression and escape.

NSCLC (non-small cell lung cancer) is the most common type of lung cancer and usually has poor prognosis. FOXP3 in regulatory T cells (Tregs) and toll-like receptor 4 (TLR4) on some tumor cells are known to be important for tumor escape and clinical tumor formation. Since FOXP3 was found recently in some tumor cells, we speculated if lung tumor cells express FOXP3 and then mimic Tregs to promote tumor escape. As TLR4 induces activation of Tregs, we also hypothesized that FOXP3 and TLR4 may have a correlation in NSCLC progression. The expression levels of FOXP3 and TLR4 protein were detected using immunohistochemistry in 53 postoperative specimens of NSCLC patients and in 15 normal lung tissues from excisions of benign lesion. The relationship between protein expression levels and clinical pathology parameters, as well as the relationship between the expression of FOXP3 and TLR4, were analyzed. FOXP3 and TLR4 expression in NSCLC were significantly elevated as compared to normal lung tissue. FOXP3 expression was closely related with lymph node metastasis and TNM staging, whereas TLR4 expression was closely related with tumor differentiation. The Spearman correlation coefficient indicated a significant positive correlation between FOXP3 and TLR4 expression. These results indicate that FOXP3 and TLR4 may coordinate to play a role in tumor escape and subsequent tumor progression.

In situ analysis of FOXP3+ regulatory T cells and myeloid dendritic cells in human colorectal cancer tissue and tumor-draining lymph node.

Forkhead box protein 3 (FOXP3) regulatory T cells (Tregs) are important in the maintenance of tumor immunity tolerance. Myeloid dendritic cells (mDCs) are antigen-presenting cells (APCs) specialized to initiate and regulate immunity. Tregs and mDCs are suspected of influencing the interaction between the tumor and immune system, and thus the course of tumors. However, the implication and interaction of their concurrent infitration in colorectal cancer (CRC) remain unknown. The aim of this study was to determine FOXP3+ Tregs and CD11c+ mDCs infiltration in CRC and tumor-draining lymph node (TDLN) and to explore the clinical and pathological implication of suppressor and effector immune cell subsets. Immunohistochemical assay was conducted to assess FOXP3+ Tregs and CD11c+ mDCs infiltration in tumor tissue and in metastasis-free TDLN (mfTDLN) and metastatic TDLN (mTDLN). The results showed that FOXP3+ Tregs and CD11c+ mDCs infiltration was higher in tumor tissue compared to adjacent normal mucosa (P<0.001). FOXP3+ Tregs infiltration was associated with advanced tumor-node-metastasis (TNM) stage and lymph node metastasis (P<0.001 and P<0.001, for TNM stage and lymph node metastasis, respectively), whereas less CD11c+ mDCs infiltration of tumor in situ was associated with deeper tumor invasion, advanced TNM stages and lymph node metastasis (P<0.05, P<0.001 and P<0.001, for tumor invasion depth, TNM stages and lymph node metastasis, respectively). Compared to mfTDLN, mTDLN was significantly enriched in FOXP3+ Tregs (P<0.001) and reduced in CD11c+ mDCs (P<0.001). The statistical analysis demonstrated no significant correlations in Tregs and mDCs infiltration. These results suggest that more FOXP3+ Tregs and less CD11c+ mDCs infiltration have stronger prognostic significance in CRC. The presence of tumor cells in mTDLN may contribute to a tolerogenic milieu and facilitate the survival of metastatic tumor cells.