[Patient with Epstein-Barr Virus-Positive Esophagogastric Junctional Cancer with Splenic Metastasis and Underwent Metastasectomy following Immune Checkpoint Therapy].

Recurrent gastric cancer(GC)with splenic metastasis showed poor prognosis, and its treatment strategy remains unclear. Recently, studies identified the considerable prognostic effect of metastasectomy in GC following intensive chemotherapy. Here, we successfully treated a patient with Epstein-Barr virus-positive esophagogastric junctional cancer with splenic metastasis who underwent metastasectomy and obtained pathological complete response following immune checkpoint therapy and had long-term survival. We reviewed the literature to discuss the clinical significance of our treatment strategy.

Generation of hypoimmunogenic induced pluripotent stem cells by CRISPR-Cas9 system and detailed evaluation for clinical application.

In order to expand the promise of regenerative medicine using allogeneic induced pluripotent stem cells (iPSCs), precise and efficient genome editing of human leukocyte antigen (HLA) genes would be advantageous to minimize the immune rejection caused by mismatches of HLA type. However, clinical-grade genome editing of multiple HLA genes in human iPSC lines remains unexplored. Here, we optimized the protocol for good manufacturing practice (GMP)-compatible CRISPR-Cas9 genome editing to deplete the three gene locus (HLA-A, HLA-B, and CIITA genes) simultaneously in HLA homozygous iPSCs. The use of HLA homozygous iPSCs has one main advantage over heterozygous iPSCs for inducing biallelic knockout by a single gRNA. RNA-seq and flow cytometry analyses confirmed the successful depletion of HLAs, and lineage-specific differentiation into cardiomyocytes was verified. We also confirmed that the pluripotency of genome-edited iPSCs was successfully maintained by the three germ layers of differentiation. Moreover, whole-genome sequencing, karyotyping, and optical genome mapping analyses revealed no evident genomic abnormalities detected in some clones, whereas unexpected copy number losses, chromosomal translocations, and complex genomic rearrangements were observed in other clones. Our results indicate the importance of multidimensional analyses to ensure the safety and quality of the genome-edited cells. The manufacturing and assessment pipelines presented here will be the basis for clinical-grade genome editing of iPSCs.

Gender differences in hip and ankle joint kinematics on knee abduction during running.

The knee is the most common site of running injuries, particularly prevalent in females. The purpose of this study was to clarify gender differences in the lower extremity kinematics during running, with a specific emphasis on the relationships between the distal and proximal factors and the knee joint kinematics. Eleven female and 11 male runners participated in this study. Three-dimensional marker positions were recorded with a motion analysis system while the subjects ran along a 25 m runway at a speed of 3.5 m/s. Kinematic variables were analyzed for the stance phase of the right leg. Female runners demonstrated significantly greater peak knee abduction (P<0.05), hip adduction (P<0.01) and internal rotation (P<0.05), whereas male runners demonstrated significantly greater peak rearfoot eversion (P<0.01). The knee abduction angles were positively correlated with hip adduction angles (r=0.49, P<0.05) and negatively correlated with rearfoot eversion (r= -0.69, P<0.001). There was no significant difference in normalised step width between genders (P>0.05). Smaller rearfoot eversion and greater hip adduction related closely to the greater knee abduction as the distal and proximal factors, respectively. These relationships are thought to be the compensatory joint motions in the frontal plane, because there was no significant difference in the normalised step width between females and males. The current results suggest that if the step width is identical, the subjects with greater knee abduction had smaller rearfoot eversion to compensate for greater hip adduction, which were more apparent in females. This explains greater knee abduction found in female runners, which can be linked to a high risk of knee injury.