Numerous proteases are known to be necessary for cancer development and progression including matrix metalloproteinases (MMPs), tissue serine proteases, and cathepsins. The goal of this research is to develop an Fe/Fe3O4 nanoparticle-based system for clinical diagnostics, which has the potential to measure the activity of cancer-associated proteases in biospecimens. Nanoparticle-based "light switches" for measuring protease activity consist of fluorescent cyanine dyes and porphyrins that are attached to Fe/Fe3O4 nanoparticles via consensus sequences. These consensus sequences can be cleaved in the presence of the correct protease, thus releasing a fluorescent dye from the Fe/Fe3O4 nanoparticle, resulting in highly sensitive (down to 1 × 10(-16) mol l(-1) for 12 proteases), selective, and fast nanoplatforms (required time: 60 min).

SummaryProteases, including matrix metalloproteinases (MMPs), tissue serine proteases, and cathepsins (CTS) exhibit numerous functions in tumor biology. Solid tumors are characterized by changes in protease expression levels by tumor and surrounding tissue. Therefore, monitoring protease levels in tissue samples and liquid biopsies is a vital strategy for early cancer detection. Water-dispersable Fe/Fe3O4-core/shell based nanoplatforms for protease detection are capable of detecting protease activity down to sub-femtomolar limits of detection. They feature one dye (tetrakis(carboxyphenyl)porphyrin (TCPP)) that is tethered to the central nanoparticle by means of a protease-cleavable consensus sequence and a second dye (Cy 5.5) that is directly linked. Based on the protease activities of urokinase plasminogen activator (uPA), MMPs 1, 2, 3, 7, 9, and 13, as well as CTS B and L, human breast cancer can be detected at stage I by means of a simple serum test. By monitoring CTS B and L stage 0 detection may be achieved. This initial study, comprised of 46 breast cancer patients and 20 apparently healthy human subjects, demonstrates the feasibility of protease-activity-based liquid biopsies for early cancer diagnosis.

MicroRNA (miRNA) are negative regulators of gene expression and subsequent protein production. This method of action translates into regulatory control over cellular processes, including development, signaling, metabolism, and apoptosis. A broad range of miRNA are shown to have abnormal expressions in thyroid cancers which could explain the pathology of tumor oncogenesis and disease progression. A review is conducted of the current research on miRNA dysregulation in thyroid cancers, including papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), anaplastic thyroid cancer (ATC), and medullary thyroid carcinoma (MTC). Dysregulated miRNA and their associated regulatory pathways are identified and their oncogenic and pathological significance are discussed.

Objective: The purpose of this article was to investigate whether the combination of urinary beta 2 microglobulin (urinary β 2 -MG) and procalcitonin (PCT) diagnosis could enhance the localization diagnostic precision of pediatric urinary tract infection comparing with single diagnosis. Methods:A study was conducted in the Nephrology Department of Wuhan women and children's health care centre. This study incorporated 85 participants, including 35 children who were diagnosed as upper urinary tract infection (UUTI) with the symptom of fever and 50 children who conducted lower urinary tract infection (LUTI).Levels of PCT and urinary β 2 -MG in both UUTI and LUTI patients were measured and compared.Results: The level of PCT and β 2 -MG were both significantly higher in UUTI group compared with in LUTI group. AUC of urinary β 2 -MG ROC (sensitivity of 71.4%, specificity of 90.0%) was significantly smaller than that of PCT ROC (sensitivity of 77.1%, specificity of 96.0%) in the single diagnosis. Although in the combined diagnosis, the sensitivity and specificity increased to 88.6% and 98%, respectively. Conclusions:Both PCT and β 2 -MG could be used to localize the UTI. Introducing urinary β 2 -MG into PCT diagnosis could increase the sensitivity and specificity of UTI lesion diagnosis in clinical practice. K E Y W O R D Schildren, localization diagnosis, procalcitonin, urinary tract infection, urinary β 2 -MG

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