Uncovering the Heterogeneity and Clinical Relevance of Circulating Tumor-Initiating Cells in Hepatocellular Carcinoma Using an Integrated Immunomagnetic-Microfluidic Platform.

Circulating tumor-initiating cells (CTICs) with stem cell-like properties play pivotal roles in tumor metastasis and recurrence. However, little is known about the biology and clinical relevance of CTICs in hepatocellular carcinoma (HCC). Here, we investigated the molecular heterogeneity and clinical relevance of CTICs in HCC using a novel integrated immunomagnetic-microfluidic platform (iMAC). We constructed the iMAC and evaluated its ability to detect CTICs using a series of spiked cell experiments. A four-channel microfluidic chip was applied to investigate the composition of CTICs in patients with primary and recurrent HCC utilizing microbeads labeled with one of four stem-related markers: epithelial cell adhesion molecule (EpCAM), CD133, CD90, and CD24. The dynamic changes of these four CTIC subsets were serially monitored during treatment courses. Finally, single-cell RNA profiling was used to reveal the molecular characteristics of the four CTIC subsets. The iMAC platform detected significantly more EpCAM+ CTICs in the blood samples from 33 HCC patients than the FDA-approved CellSearch system (0.92 ± 0.94 vs 0.23 ± 0.36, P < 0.001). The number of EpCAM+ CTICs (≥0.75/mL) detected by iMAC was a predictor of early recurrence (P = 0.007). The distinct stem-related markers' expression of CTICs could distinguish primary HCC, recurrent HCC, and TACE-resistant HCC. Single-cell transcriptional profiling proved the heterogeneity among individual CTICs and separated the four CTIC subsets into distinct phenotypes. Dissecting the heterogeneity of CTICs using the iMAC represents a novel and informative method for accurate CTIC detection and characterization. This innovative technology will enable more indepth cancer biology research and clinical cancer management than is currently available.

Effects of high temperature on children s emergency admissions during summer from 2016 to 2018 in Beijing / 中国学校卫生

Objective@#To explore the adverse effects of high temperature on emergency admissions of children during the summer in Beijing.@*Methods@#Child emergency admissions was collected from 30 hospitals in Beijing during the summer of 2016-2018, as well as data related to meteorological factors and air pollutant concentrations. A generalized linear model was used to analyze the association between the daily mean temperature and emergency admissions of children due to total non accidental diseases, circulatory diseases, and respiratory diseases during the summer in Beijing.@*Results@#During the summer of 2016 to 2018 in Beijing, the daily mean temperature was (24.06±3.59)℃, and the daily mean relative humidity was (65.08±17.45)%. Every 1 ℃ increase in the daily mean temperature on the day of exposure had a significant effect on emergency admissions of children, aged 0-14 years old, due to total non accidental diseases and respiratory diseases in Beijing, such that the risk of emergency admissions increased by 0.21, 0.64 times, respectively. The effect of high temperature on emergency admissions due to circulatory diseases was not significant. High temperature had inconsistent effects on emergency admissions of children from different age groups. Among them, the largest increase in the risk of emergency admissions due to total non accidental diseases was observed among children aged 5-9 years old, while children aged 0-4 were vulnerable to emergency admissions for respiratory diseases, and emergency admissions for circulatory diseases were the highest among children aged 10-14.@*Conclusion@#High temperature had a significant effect on emergency admissions of children during the summer in Beijing. Pediatric respiratory diseases are sensitive diseases that are associated with a high temperature in summer, and greater attention should be given to this issue.

Recent Advance in Source, Property, Differentiation, and Applications of Infrapatellar Fat Pad Adipose-Derived Stem Cells.

Infrapatellar fat pad (IPFP) can be easily obtained during knee surgery, which avoids the damage to patients for obtaining IPFP. Infrapatellar fat pad adipose-derived stem cells (IPFP-ASCs) are also called infrapatellar fat pad mesenchymal stem cells (IPFP-MSCs) because the morphology of IPFP-ASCs is similar to that of bone marrow mesenchymal stem cells (BM-MSCs). IPFP-ASCs are attracting more and more attention due to their characteristics suitable to regenerative medicine such as strong proliferation and differentiation, anti-inflammation, antiaging, secreting cytokines, multipotential capacity, and 3D culture. IPFP-ASCs can repair articular cartilage and relieve the pain caused by osteoarthritis, so most of IPFP-related review articles focus on osteoarthritis. This article reviews the anatomy and function of IPFP, as well as the discovery, amplification, multipotential capacity, and application of IPFP-ASCs in order to explain why IPFP-ASC is a superior stem cell source in regenerative medicine.