Chuan Hu

Background: Autophagy-related genes (ARGs) have been confirmed to have an important role in tumorigenesis and tumor microenvironment formation. Nevertheless, a systematic analysis of ARGs and their clinical significance in sarcoma patients is lacking. Methods: Gene expression files from The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx) were used to select differentially expressed genes (DEGs). Differentially expressed ARGs (DEARGs) were determined by matching the DEG and HADb gene sets, which were evaluated by functional enrichment analysis. Unsupervised clustering of the identified DEARGs was conducted, and associations with tumor microenvironment (TME), immune checkpoints, and immune cells were analyzed simultaneously. Two prognostic signatures, one for overall survival (OS) and one for disease-free survival (DFS), were established and validated in an independent set. Results: In total, 84 DEARGs and two clusters were identified. TME scores, five immune checkpoints, and several types of immune cells were found to be significantly different between two clusters. Two prognostic signatures incorporating DEARGs showed favorable discrimination and were successfully validated. Two nomograms combining signature and clinical variables were generated. The C-indexes were 0.818 and 0.747 for the OS and DFS nomograms, respectively. Conclusion: This comprehensive analyses of the ARG landscape in sarcoma showed novel ARGs related to carcinogenesis and the immune microenvironment. These findings have implications for prognosis and therapeutic responses, which reveal novel potential prognostic biomarkers, promote precision medicine, and provide potential novel targets for immunotherapy.

Background: Autophagy-related genes (ARGs) have been confirmed to have an important role in tumorigenesis and tumor microenvironment formation. Nevertheless, a systematic analysis of ARGs and their clinical significance in sarcoma patients is lacking.Methods: Gene expression files from The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx) were used to select differentially expressed genes (DEGs). Differentially expressed ARGs (DEARGs) were determined by matching the DEG and HADb gene sets, which were evaluated by functional enrichment analysis. Unsupervised clustering of the identified DEARGs was conducted, and associations with tumor microenvironment (TME), immune checkpoints, and immune cells were analyzed simultaneously. Two prognostic signatures, one for overall survival (OS) and one for disease-free survival (DFS), were established and validated in an independent set. Results: In total, 84 DEIRGs and two clusters were identified. TME scores, five immune checkpoints, and several types of immune cells were found to be significantly different between twp clusters. Two prognostic signatures incorporating DEARGs showed favorable discrimination and were successfully validated. Two nomograms combining signature and clinical variables were generated. The C-indexes were 0.818 and 0.636 for the OS and DFS nomograms, respectively.Conclusion: This comprehensive analyses of the ARG landscape in sarcoma showed novel ARGs related to carcinogenesis and the immune microenvironment. These findings have implications for prognosis and therapeutic responses, which reveal novel potential prognostic biomarkers, promote precision medicine, and provide potential novel targets for immunotherapy.

The incidence, risk factors, and associated complications of perioperative transfusion in nonfracture patients following total hip arthroplasty (THA) are unclear. The aim of the present research was to study the predictors of transfusion risk in nonfracture patients following THA and develop a nomogram. One thousand six hundred and thirty‐five patients who underwent THA due to nonfracture disease in our institution between September 2013 and July 2017 were included. Independent predictors of transfusion were identified by univariate, LASSO, and multivariate analyses. A nomogram was established based on independent predictors. In addition, a prospective cohort was used to validate the nomogram. The area under the receiver operating characteristic curve was utilized to evaluate the discrimination of the nomogram. Calibration and decision curve analyses were established to evaluate the nomogram. In addition, the association between perioperative transfusion and 30‐ and 90‐day complications was studied. The incidence of transfusion was 15.78%, and 10 independent predictors were confirmed. The areas under the curve of the nomogram were 0.834 and 0.867 in the training and validation cohorts, respectively. Moreover, the area under the curve of the nomogram was significantly higher than that of any single predictor in both the training and validation cohorts. Calibration curve and decision curve analyses in both the training and validation cohorts showed good performance of the nomogram. In addition, perioperative transfusion was identified as an independent risk factor for both 30‐ and 90‐day complications. Generally, ten transfusion‐related factors for nonfracture patients following THA were identified. A validated nomogram was established, and several adverse events were confirmed to be associated with transfusion.

Background: The purpose of this study was to investigate the incidence and timing of postoperative symptomatic pulmonary embolism (PE) in patients receiving non-warfarin following primary total joint arthroplasty (TJA), to clarify the appropriate duration of postoperative VTE prophylaxis. Methods: We retrospectively reviewed the medical records of 11148 patients who underwent primary TJA, including total knee arthroplasty (TKA) and total hip arthroplasty (THA) at our institution from January 2012 to March 2019. The median postoperative day of diagnosis of symptomatic PE and interquartile range for day of diagnosis were determined. Multivariate Cox proportional hazards modeling was used to test the difference of timing for PE based on demographics and comorbidities. Results: The overall 90-day rate of symptomatic PE was 0.71%. The median day of diagnosis for symptomatic PE was 3 day postoperatively (interquartile: 2–7 day). Factors that showed statistical significance on multivariate analysis in association with earlier timing of PE occurrence in patients with atrial fibrillation, diabetes mellitus, coronary heart disease and history of stroke. Conclusion: The vast majority symptomatic PE occurs in the early postoperative period after TJA, and atrial fibrillation, diabetes mellitus, coronary heart disease and history of stroke were independent factors affecting the timing of symptomatic PE.

Notch signaling is an evolutionarily conserved pathway, which involves in various cell life activities. Other studies and our report showed that the Notch signaling plays very important role in follicle development in mammalian ovaries. In luteal cells, Notch ligand, delta-like ligand 4, is involved in normal luteal vasculature. In this study, murine luteal cells were cultured in vitro and treated with Notch signaling inhibitors, L-658,458 and N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycinet-butyl ester (DAPT). We found that L-658,458 and DAPT treatment decrease basal and human chorionic gonadotropin (hCG)-stimulated progesterone secretion. On the contrary, overexpression of intracellular domain of Notch3 increased basal and hCG-stimulated progesterone secretion. Further studies demonstrated that Notch signaling regulated the expression of steroidogenic acute regulatory protein and CYP11A, 2 key enzymes for progesterone synthesis. In conclusion, Notch signaling plays important role in regulating progesterone secretion in murine luteal cells.