Surgical Outcomes of Posterior Short Segment Fixation for Thoracolumbar Burst Fractures: A Study of Patients Treated without Vertebroplasty

There is no widespread agreement regarding the treatment of thoracolumbar burst fractures. While performing posterior short segment fixation of thoracolumbar burst fractures, we evaluated therapeutic outcomes in patients treated with screw insertion into fractured vertebral bodies without vertebroplasty. We also investigated the limitations associated with the treatment of burst fractures when vertebroplasty is not performed. Twenty-one of 51 patients with thoracolumbar burst fractures who were treated surgically in Ohta Nishinouchi Hospital were evaluated in the present study. These patients underwent posterior short segment fixation with screw insertion into the fractured vertebral bodies (only pedicle screws were inserted one level above and one level below the fractured vertebral bodies) without vertebroplasty. Vertebral angles were measured before surgery, immediately after surgery, and at the final follow-up examination. Changes in vertebral angles were compared and analyzed. The mean vertebral angles before and after surgery and at the final follow-up examination were 15.4°, 6.6°, and 9.1°, respectively. The mean postoperative correction loss was 2.5°. The therapeutic outcomes of posterior short segment fixation with screw insertion into fractured vertebral bodies without vertebroplasty were generally favorable

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Analysis of miRNA Expression in Breast Cancer

Triple-negative breast cancer (TNBC), lacking estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor (HER2) expression, is resistant to conventional therapies. Recent studies have focused on microRNAs (miRNAs) as novel molecular targets for treating TNBC because they modulate gene expression and tumor progression. In the current study, we analyzed the expression of selected miRNAs (miR-145 and miR-182) and tumor promoting factors such as Fascin and poly (ADP-ribose) polymerase (PARP) in human TNBC tissues and "Luminal A" breast cancer tissues, which express ER and PgR, but not HER2, as well as breast cancer cell lines including the triple-negative MDA-MB-231 and Luminal A MCF-7. The results showed that miR-145 and miR-182 were expressed in Luminal A breast cancer tissues and MCF-7 cells, but not in TNBC tissues and MDA-MB-231 cells. In contrast, Fascin and PARP proteins were highly expressed in TNBC and MDA-MB-231, but poorly expressed in Luminal A tissues and MCF-7 cells, indicating a negative correlation between expression of these miRNAs and that of the tumor promoting factors Fascin and PARP. The current study therefore suggests that miR-145 and miR-182 could be potential novel therapeutic targets for TNBC therapy