Platelet RNA enables accurate detection of ovarian cancer: an intercontinental, biomarker identification study

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.

Transcriptome and Regulatory Network Analyses of CD19-CAR-T Immunotherapy for B-ALL / 基因组蛋白质组与生物信息学报·英文版

Chimeric antigen receptor (CAR) T cell therapy has exhibited dramatic anti-tumor efficacy in clinical trials. In this study, we reported the transcriptome profiles of bone marrow cells in four B cell acute lymphoblastic leukemia (B-ALL) patients before and after CD19-specific CAR-T therapy. CD19-CAR-T therapy remarkably reduced the number of leukemia cells, and three patients achieved bone marrow remission (minimal residual disease negative). The efficacy of CD19-CAR-T therapy on B-ALL was positively correlated with the abundance of CAR and immune cell subpopulations, e.g., CD8 T cells and natural killer (NK) cells, in the bone marrow. Additionally, CD19-CAR-T therapy mainly influenced the expression of genes linked to cell cycle and immune response pathways, including the NK cell mediated cytotoxicity and NOD-like receptor signaling pathways. The regulatory network analyses revealed that microRNAs (e.g., miR-148a-3p and miR-375), acting as oncogenes or tumor suppressors, could regulate the crosstalk between the genes encoding transcription factors (TFs; e.g., JUN and FOS) and histones (e.g., HIST1H4A and HIST2H4A) involved in CD19-CAR-T therapy. Furthermore, many long non-coding RNAs showed a high degree of co-expression with TFs or histones (e.g., FOS and HIST1H4B) and were associated with immune processes. These transcriptome analyses provided important clues for further understanding the gene expression and related mechanisms underlying the efficacy of CAR-T immunotherapy.

Surgical treatment of tibia Pilon fractures / 中国骨伤

<p><b>OBJECTIVE</b>To evaluate the choice of operative method,timing of surgery and the outcome of tibia Pilon fractures.</p><p><b>METHODS</b>From March 1999 to November 2008, 52 patients of Pilon fractures were treated including 38 males and 14 females with the average age of 38 years old ranging from 23 to 59 years. There were 17 cases of open fractures and 35 cases of closed fractures. According to Ruedi-Allgower type,there were 6 cases of type I fracture, 29 cases of type II, 17 cases of type III. Thirty-three cases selected emergency surgery and 19 cases selected the selective operation, the average period between injury and surgery was 8.3 days. According to the type of fracture, open reduction and plate fixation of Trilobal, limited internal fixation combined with external fixation were applied for treatment of different surgical methods.</p><p><b>RESULTS</b>All patients were followed-up for from 10 to 55 months (averaged 28 months). According to Mazur's criterion, the result of treatment was evaluated as excellent in 28 cases,good in 14 and fair in 10. After operation, 5 cases occurrenced skin and soft tissue infection and necrosis, 1 case of nonunion healed again after bone graft in re-operation, 6 patients occurrenced ankle traumatic arthritis later.</p><p><b>CONCLUSION</b>According to fracture type, degree of injury and timely and effective surgical treatment is the key to achieve a satisfactory effect, which can effectively avoid the occurrence of complications.</p>