The past decade has witnessed ongoing progress in precision medicine to improve human health. As an emerging diagnostic technique, liquid biopsy can provide realtime, comprehensive, dynamic physiological and pathological information in a noninvasive manner, opening a new window for precision medicine. Liquid biopsy depends on the sensitive and reliable detection of circulating targets (e.g., cells, extracellular vesicles, proteins, microRNAs) from body fluids, the performance of which is largely governed by recognition ligands. Aptamers are single-stranded functional oligonucleotides, capable of folding into unique tertiary structures to bind to their targets with superior specificity and affinity. Their mature evolution procedure, facile modification, and affinity regulation, as well as versatile structural design and engineering, make aptamers ideal recognition ligands for liquid biopsy. In this review, we present a broad overview of aptamer-based liquid biopsy techniques for precision medicine. We begin with recent advances in aptamer selection, followed by a summary of state-of-the-art strategies for multivalent aptamer assembly and aptamer interface modification. We will further describe aptamer-based micro-/nanoisolation platforms, aptamer-enabled release methods, and aptamer-assisted signal amplification and detection strategies. Finally, we present our perspectives regarding the opportunities and challenges of aptamer-based liquid biopsy for precision medicine.

Due to growing throughput and shrinking cost, massively parallel sequencing is rapidly becoming an attractive alternative to microarrays for the genome-wide study of gene expression and copy number alterations in primary tumors. The sequencing of transcripts (RNA-Seq) should offer several advantages over microarray-based methods, including the ability to detect somatic mutations and accurately measure allele-specific expression. To investigate these advantages we have applied a novel, strand-specific RNA-Seq method to tumors and matched normal tissue from three patients with oral squamous cell carcinomas. Additionally, to better understand the genomic determinants of the gene expression changes observed, we have sequenced the tumor and normal genomes of one of these patients. We demonstrate here that our RNA-Seq method accurately measures allelic imbalance and that measurement on the genome-wide scale yields novel insights into cancer etiology. As expected, the set of genes differentially expressed in the tumors is enriched for cell adhesion and differentiation functions, but, unexpectedly, the set of allelically imbalanced genes is also enriched for these same cancer-related functions. By comparing the transcriptomic perturbations observed in one patient to his underlying normal and tumor genomes, we find that allelic imbalance in the tumor is associated with copy number mutations and that copy number mutations are, in turn, strongly associated with changes in transcript abundance. These results support a model in which allele-specific deletions and duplications drive allele-specific changes in gene expression in the developing tumor.

With the rapid increase in the use of thoracic pedicle screws in scoliosis, accurate and safe placement of screw within the pedicle is a crucial step during the scoliosis surgery. To make thoracic pedicle screw placement safer various techniques are used, Patient-specific drill template with pre-planned trajectory has been thought as a promising solution, it is critical to assess the efficacy, safety profile with this technique. In this paper, we develop and validate the accuracy and safety of thoracic transpedicular screw placement with patient-specific drill template technique in scoliosis. Patients with scoliosis requiring instrumentation were recruited. Volumetric CT scan was performed on each desired thoracic vertebra and a 3-D reconstruction model was generated from the CT scan data. The optimal screw size and orientation were determined and a drill template was designed with a surface that is the inverse of the posterior vertebral surface. The drill template and its corresponding vertebra were manufactured using rapid prototyping technique and tested for violations. The navigational template was sterilized and used intraoperatively to assist with the placement of thoracic screws. After surgery, the positions of the pedicle screws were evaluated using CT scan and graded for validation. This method showed its ability to customize the placement and the size of each pedicle screw based on the unique morphology of the thoracic vertebra. In all the cases, it was relatively very easy to manually place the drill template on the lamina of the vertebral body during the surgery. This method significantly reduces the operation time and radiation exposure for the members of the surgical team, making it a practical, simple and safe method. The potential use of such a navigational template to insert thoracic pedicle screws in scoliosis is promising. The use of surgical navigation system successfully reduced the perforation rate and insertion angle errors, demonstrating the clear advantage in safe and accurate pedicle screw placement of scoliosis surgery.

This study demonstrates a patient-specific template technique that is easy to use, can simplify the surgical act, and generates highly accurate cervical pedicle screw placement. The advantages of this technology over traditional techniques are that it enables planning of the screw trajectory to be completed prior to surgery, and that the screw can be sized to fit the patient's anatomy.