Tumor metastasis is attributed to circulating tumor cells (CTC) or CTC clusters. Many strategies have hitherto been designed to isolate CTCs, but there are few methods that can capture and gently release CTC clusters as efficient as single CTCs. Herein, we developed a three-dimensional (3D) scaffold chip with thermosensitive coating for high-efficiency capture and release of individual and cluster CTCs. The 3D scaffold chip successfully combines the specific recognition and physically obstructed effect of 3D scaffold structure to significantly improve cell clusters capture efficiency. Thermosensitive gelatin hydrogel uniformly coated on the scaffold dissolves at 37 °C quickly, and the captured cells are gently released from chip with high viability. Notably, this platform was applied to isolate CTCs from cancer patients' blood samples. This allows global DNA and RNA methylation analysis of collected single CTC and CTC clusters, indicating the great potential of this platform in cancer diagnosis and downstream analysis at the molecular level.

Effective isolation of circulating tumor cells (CTCs) has great significance for cancer research but is highly challenged. Here, we developed a microchip embedded with a three-dimensional (3D) PDMS scaffold by a quadratic-sacrificing template method for high-efficiency capture of CTCs. The microchip was gifted with a 3D interconnected macroporous structure, strong toughness, and excellent flexibility and transparency, enabling fast isolation and convenient observation of CTCs. Especially, 3D scaffold chip perfectly integrates the two main strategies currently used for enhancement of cell capture efficiency. Spatially distributed 3D scaffold compels cells undergoing chaotic or vortex migration in the channel, and the spatially distributed nanorough skeleton offers ample binding sites, which synergistically and significantly improve CTCs capture efficiency. Our results showed that 1-118 CTCs/mL were identified from 14 cancer patients' blood and 5 out of these cancer patients showed 1-14 CTC clusters/mL. This work demonstrates for the first time the development of microchip with transparent interconnected 3D scaffold for isolation of CTCs and CTC clusters, which may promote in-depth analysis of CTCs.

Background: Overhydration is common among peritoneal dialysis (PD) patients and can affect PD-related outcomes. This paper aims to systematically investigate whether bioimpedance-assessed overhydration is a predictor for mortality and technique failure in PD patients. Methods: We conducted a systematic review and meta-analysis of cohort studies on overhydration and prognosis in PD patients, strictly complying with the Preferred Reporting Items for Systematical Reviews and Meta-analyses. Results: Eight articles met the selection criteria and 5 studies were included in the meta-analysis. Meta-analyses-revealed overhydration, defined as a high ratio of extracellular water/total body water (ECW/TBW), was significantly associated with higher risk for all-cause mortality and technique failure. Other higher dichotomized overhydration indicators and continuous hydration variables all indicated overhydration as a significant risk factor for all-cause mortality. Conclusion: Overhydration, defined by a higher ratio of ECW/TBW, might be an independent predictor for all-cause mortality and technique failure among PD patients. However, more studies are needed to confirm this conclusion. Video Journal Club ‘Cappuccino with Claudio Ronco’ at https://www.karger.com/Journal/ArticleNews/223997?​sponsor=52

DIS3-like 3 0-5 0 exoribonuclease 2 (DIS3L2) degrades aberrant RNAs, however, its function in tumorigenesis remains largely unexplored. Here, aberrant DIS3L2 expression promoted human hepatocellular carcinoma (HCC) progression via heterogeneous nuclear ribonucleoproteins (hnRNP) U-mediated alternative splicing. DIS3L2 directly interacted with hnRNP U through its cold-shock domains and promoted inclusion of exon 3b during splicing of pre-Rac1 independent of its exonuclease activity, yielding an oncogenic splicing variant, Rac1b, which is known to stimulate cellular transformation and tumorigenesis. DIS3L2 regulated alternative splicing by recruiting hnRNP U to pre-Rac1. Rac1b was critical for DIS3L2 promotion of liver cancer development both in vitro and in vivo. Importantly, DIS3L2 and Rac1b expression highly correlated with HCC progression and patient survival. Taken together, our findings uncover an oncogenic role of DIS3L2, in which it promotes liver cancer progression through a previously unappreciated mechanism of regulating hnRNP U-mediated alterative splicing. Significance: These findings establish the role and mechanism of the 3 0-5 0 exoribonuclease DIS3L2 in hepatocellular carcinoma carcinogenesis.