摘要
Objective:To screen T-cell exhaustion-related signature genes as the prognostic marker for osteosarcoma and establish a prognostic model for osteosarcoma patients based on weighted gene co-expression network analysis(WGCNA)and Least absolute shrinkage and selection operator(LASSO)-COX regression analysis. Methods:GSE21257 dataset was downloaded from Gene Expression Omnibus(GEO)database for the establishment of the prognostic model for osteosarcoma.4 T-cell exhaustion-related gene sets were downloaded from The Molecular Signatures Database(MisgDB)and their enrichment scores in GSE21257 samples were calculated by single sample gene set enrichment analysis(ssGSEA).WGCNA was carried out to screen the gene module that is highly associated with T-cell exhaustion based on ssGSEA results followed by GO(Gene Ontology)and KEGG(Kyoto Encyclopedia of Genes and Genomes)analysis of the biological processes and signaling transduction pathways that those genes are involved in.The signature genes that are highly associated with the prognosis of osteosarcoma patients were obtained through LASSO-COX regression and a prognostic model was established based on these signature genes.Osteosarcoma-related expression profile data from the GSE21257 and TAEGET datasets on XENA were downloaded from the Gene Expression Omnibus.Clinical information for the training and validation sets was obtained.T-cell exhaustion-related genes were screened using a weighted correlation network analysis.Realtime fluorescence quantitative PCR,COX regression analysis,external dataset and nomogram were used to evaluate the reliability and accuracy of the prognostic model.A immunotherapy-related dataset was used to assess the efficacy of this prognostic model for the prediction of patients'responses to immunotherapy. Results:Analysis results based on the ssGSEA scores showed that T-cell exhaustion-related genes were related to the metastasis and age of osteosarcoma patients.Many T-cell exhaustion-related genes were found to be differentially expressed in metastatic and non-metastatic osteosarcoma patients.1 256 T-cell exhaustion-related genes were identified through WGCNA and these candidate markers were mainly distributed in structures like secretory granule membranes and endocytic vesicles and were involved in T-cell activation.COX regression analysis screened 68 significant prognostic markers out of the 1 256 genes,and 12 signature genes were further confirmed with LASSO-COX regression analysis.A prognostic model was established based on the 12 signature genes.Results of real-time fluorescence quantitative PCR showed a similar trend in the expression of most of the signature genes in different osteosarcoma cell lines.COX regression analysis of the internal and external datasets verified that the risk score calculated with the prognostic model was an independent prognostic factor for osteosarcoma patients,and high-risk score was associated with poor prognosis of the patients.Receiver operating characteristic(ROC)curves demonstrated excellent prognostic efficacy of the model.Nomogram analysis verified the prognostic model is highly accurate and reliable in predicting the prognosis of osteosarcoma patients.Analysis using the immunotherapy-related dataset indicated that this prognostic model could also be used to predict patients'responses to immunotherapy. Conclusion:The 12 signature gene(CD300LB,TRO,SNX3,VENTX,PPM1M,DOT1L,CDC37,NAT9,TRMT1,PPP1R3C,CHTF18 and NSUN5)-based prognostic model can effectively predict the prognosis and responses to immune check-point inhibitors for osteosarcoma patients,which may provide evidence for the prediction of prognosis as well as the selection of immunotherapy plans in clinical practice.
摘要
Thirty-six puerperas who underwent emergency cesarean section at Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology from January 24, 2020 to February 9, 2020, who all wore medical surgical masks, were retrospectively included in this study.Anesthesia management was performed under tertiary medical protection measures.A dedicated anesthesia equipment was separately sterilized.Narcotic drugs were used for one patient only, and disposable medical supplies were used for anesthetic supplies.Contact transmission should be avoided when a neonate required resuscitation, and early isolation and nucleic acid testing were provided for the neonates.The rate of suspected cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was 11% , and the rate of clinically diagnosed cases was 17% before surgery.The rate of clinically diagnosed cases of SARS-CoV-2 was 22%, the rate of confirmed cases was 8%, and the total positive rate of diagnosis was 31% after surgery.The rate of neuraxial anesthesia was 86%, the rate of general anesthesia was 14%, the time of spinal puncture was (15±7) min, the time of tracheal intubation under general anesthesia was (2.1±1.3) min, the operation time was (95±36) min, and blood loss was (276±166) ml.The Apgar score of newborns was 8.8±0.5.There was 1 neonate whose mother was diagnosed as having coronavirus disease 2019 after operation, an oropharyngeal swab specimen was obtained at 36 h of birth, and the swab was tested positive for SARS-CoV-2 by nucleic acid testing.As of February 10, 2020, an anesthesiologist involved in the operation was diagnosed to have infection by SARS-CoV-2.In conclusion, diagnosis of coronavirus disease 2019 during pregnancy is more difficult, it is necessary to perform anesthesia management for cesarean section under tertiary medical protection.Although the difficulty in anesthesia operation is increased under tertiary medical protection, anesthesiologists can carry out standardized anesthesia management and guarantee the safety of maternal and infants and anesthesiologists themselves as long as they are rigorously trained and adhere to protective protocols.
摘要
Objective: To investigate the effect of pleiotrophin (PTN) on the chemotherapy resistance of osteosarcoma cells, and its possible molecular mechanism. Methods: The expression levels of PTN and microRNA (miR)-137-3p in osteosarcoma drug-resistant MG63/ADR cells and parental MG63 cells were detected by real-time fluorescent quantitative PCR. SiRNA-PTN or miR-137-3p mimic was transfected into MG63/ADR cells, while the PTN recombinant plasmid or miR-137-3p inhibitor was transfected into MG63 cells. After the transfection efficiency was verified by real-time fluorescent quantitative PCR, the cell proliferation activity was detected by CCK-8 and clony formation assay. The interaction between miR-1373p and the target gene PTN was verified by dual luciferase reporter gene system. The miR-137-3p mimic, siRNA-PTN or miR-137-3p mimic+PTN recombinant plasmid was respectively transfected into osteosarcoma MG63/ADR cells, then the expressions of PTN mRNA and protein were detected by real-time fluorescent quantitative PCR and Western blotting, and the cell viability was detected by CCK-8 method. Results: PTN was significantly highly expressed in drug-resistant MG63/ ADR cells (P < 0.01), while miR-137-3p was significantly lowly expressed (P < 0.01). After transfection with siRNA-PTN or miR-137-3p mimic, the proliferation and clone formation abilities of MG63/ADR cells were significantly reduced (all P < 0.01). After transfection with PTN vector or miR-137-3p inhibitor, the proliferation and clone formation abilities of parental MG63 cells were significantly increased (all P < 0.01). PTN was a downstream target gene of miR-137-3p, and miR-137-3p negatively regulated the expression of PTN gene (P < 0.01). After transfection with siRNA-PTN or miR-137-3p mimic, the expression levels of PTN mRNA and protein in MG63/ADR cells were reduced (both P < 0.01), but the overexpression of PTN could reverse the effect of miR-137-3p on the viability of osteosarcoma drug-resistant cells (P < 0.01). Conclusion: PTN can regulate the chemotherapy resistance of osteosarcoma, and its mechanism may be related to miR-137-3p downregulating PTN expression.
摘要
Thirty-six puerperas who underwent emergency cesarean section at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 24, 2020 to February 9, 2020, who all wore medical surgical masks, were retrospectively included in this study. Anesthesia management was performed under tertiary medical protection measures. A dedicated anesthesia equipment was separately sterilized. Narcotic drugs were used for one patient only, and disposable medical supplies were used for anesthetic supplies. Contact transmission should be avoided when a neonate required resuscitation, and early isolation and nucleic acid testing were provided for the neonates. The rate of suspected cases of novel coronavirus (2019-nCoV) was 11% , and the rate of clinically diagnosed cases was 17% before surgery. The rate of clinically diagnosed cases of 2019-nCoV was 22%, the rate of confirmed cases was 8%, and the total positive rate of diagnosis was 31% after surgery. The rate of neuraxial anesthesia was 86%, the rate of general anesthesia was 14%, the time of spinal puncture was (15±7) min, the time of tracheal intubation under general anesthesia was (2.1±1.3) min, the operation time was (95±36) min, and blood loss was (276±166) ml. The Apgar score of newborns was 8.8 ± 0.5. There was 1 neonate whose mother was diagnosed as having 2019 novel coronavirous disease after operation, an oropharyngeal swab specimen was obtained at 36 h of birth, and the swab was tested positive for 2019-nCoV by nucleic acid testing. As of February 10, 2020, an anesthesiologist involved in the operation was diagnosed to have infection by 2019-nCoV. In conclusion, diagnosis of 2019 novel coronavirous disease during pregnancy is more difficult, it is necessary to perform anesthesia management for cesarean section under tertiary medical protection. Although the difficulty in anesthesia operation is increased under tertiary medical protection, anesthesiologists can carry out standardized anesthesia management and guarantee the safety of maternal and infants and anesthesiologists themselves as long as they are rigorously trained and adhere to protective protocols.
摘要
Objective To investigate the clinical features, diagnosis, treatment and outcome of patients with Takayasu arteritis associated pulmonary hypertension (TA-PH). Methods Patients diagnosed as TA-PH in Shanghai Pulmonary hospital from 2008 to 2017 were retrospectively reviewed and followed up. Baseline characteristics including hemodynamics were collected. Data were summarized as mean ± standard deviation or frequency (％). Survival analyses were performed using the Kaplan-Meier method. Results Thirteen TA-PH patients (10 female, aged 39±11 years old) were included. The duration from symptoms onset to diagnosis was 2 months to 50 years, and ten patients were diagnosed TA and PH at the same time. Shortness of breath was the most common clinical manifestation (12 cases), followed by chest pain and tightness (8 cases) and palpitation (6 cases). All patients had a moderated WHO functional class and 8 patients were in active phase. Vessel wall thickening, lumen narrowing, occlusion and/or dilation were found in CT pulmonary angiography and angiography. Mean pulmonary arterial pressure (48.0±14.0) mmHg and pulmonary vascular resistant (7.59±4.21) Wood U were increased. All patients received PH-specific therapies, and patients at active status took glucocorticoid. Stentimplantation in pulmonary artery was performed in 4 patients. Three patients died during the follow-up. Conclusions Patients with TA are at risk of PH, and PH can be the first manifestation of TA, which suggest that PH should be screened regularly in patients with TA and shortness of breath. The prognosis of TA-PH is poor. PH-specific therapies and vascular reconstruction therapy may be effective, but need further investigation.