Construction of a Prognostic Model of Multiple Myeloma Based on Metabolism-Related Genes / 中国实验血液学杂志

OBJECTIVE@#To screen the prognostic biomarkers of metabolic genes in patients with multiple myeloma (MM), and construct a prognostic model of metabolic genes.@*METHODS@#The histological database related to MM patients was searched. Data from MM patients and healthy controls with complete clinical information were selected for analysis.The second generation sequencing data and clinical information of bone marrow tissue of MM patients and healthy controls were collected from human protein atlas (HPA) and multiple myeloma research foundation (MMRF) databases. The gene set of metabolism-related pathways was extracted from Molecular Signatures Database (MSigDB) by Perl language. The biomarkers related to MM metabolism were screened by difference analysis, univariate Cox risk regression analysis and LASSO regression analysis, and the risk prognostic model and Nomogram were constructed. Risk curve and survival curve were used to verify the grouping effect of the model. Gene set enrichment analysis (GSEA) was used to study the difference of biological pathway enrichment between high risk group and low risk group. Multivariate Cox risk regression analysis was used to verify the independent prognostic ability of risk score.@*RESULTS@#A total of 8 mRNAs which were significantly related to the survival and prognosis of MM patients were obtained (P<0.01). As molecular markers, MM patients could be divided into high-risk group and low-risk group. Survival curve and risk curve showed that the overall survival time of patients in the low-risk group was significantly better than that in the high risk group (P<0.001). GSEA results showed that signal pathways related to basic metabolism, cell differentiation and cell cycle were significantly enriched in the high-risk group, while ribosome and N polysaccharide biosynthesis signaling pathway were more enriched in the low-risk group. Multivariate Cox regression analysis showed that the risk score composed of the eight metabolism-related genes could be used as an independent risk factor for the prognosis of MM patients, and receiver operating characteristic curve (ROC) showed that the molecular signatures of metabolism-related genes had the best predictive effect.@*CONCLUSION@#Metabolism-related pathways play an important role in the pathogenesis and prognosis of patients with MM. The clinical significance of the risk assessment model for patients with MM constructed based on eight metabolism-related core genes needs to be confirmed by further clinical studies.

Exploration of omics mechanism and drug prediction of coronavirus-induced heart failure based on clinical bioinformatics / 中华心血管病杂志

Objective: Present study investigated the mechanism of heart failure associated with coronavirus infection and predicted potential effective therapeutic drugs against heart failure associated with coronavirus infection. Methods: Coronavirus and heart failure were searched in the Gene Expression Omnibus (GEO) and omics data were selected to meet experimental requirements. Differentially expressed genes were analyzed using the Limma package in R language to screen for differentially expressed genes. The two sets of differential genes were introduced into the R language cluster Profiler package for gene ontology (GO) and Kyoto gene and genome encyclopedia (KEGG) pathway enrichment analysis. Two sets of intersections were taken. A protein interaction network was constructed for all differentially expressed genes using STRING database and core genes were screened. Finally, the apparently accurate treatment prediction platform (EpiMed) independently developed by the team was used to predict the therapeutic drug. Results: The GSE59185 coronavirus data set was searched and screened in the GEO database, and divided into wt group, ΔE group, Δ3 group, Δ5 group according to different subtypes, and compared with control group. After the difference analysis, 191 up-regulated genes and 18 down-regulated genes were defined. The GEO126062 heart failure data set was retrieved and screened from the GEO database. A total of 495 differentially expressed genes were screened, of which 165 were up-regulated and 330 were down-regulated. Correlation analysis of differentially expressed genes between coronavirus and heart failure was performed. After cross processing, there were 20 GO entries, which were mainly enriched in virus response, virus defense response, type Ⅰ interferon response, γ interferon regulation, innate immune response regulation, negative regulation of virus life cycle, replication regulation of viral genome, etc. There were 5 KEGG pathways, mainly interacting with tumor necrosis factor (TNF) signaling pathway, interleukin (IL)-17 signaling pathway, cytokine and receptor interaction, Toll-like receptor signaling pathway, human giant cells viral infection related. All differentially expressed genes were introduced into the STRING online analysis website for protein interaction network analysis, and core genes such as signal transducer and activator of transcription 3, IL-10, IL17, TNF, interferon regulatory factor 9, 2'-5'-oligoadenylate synthetase 1, mitogen-activated protein kinase 3, radical s-adenosyl methionine domain containing 2, c-x-c motif chemokine ligand 10, caspase 3 and other genes were screened. The drugs predicted by EpiMed's apparent precision treatment prediction platform for disease-drug association analysis were mainly TNF-α inhibitors, resveratrol, ritonavir, paeony, retinoic acid, forsythia, and houttuynia cordata. Conclusions: The abnormal activation of multiple inflammatory pathways may be the cause of heart failure in patients after coronavirus infection. Resveratrol, ritonavir, retinoic acid, amaranth, forsythia, houttuynia may have therapeutic effects. Future basic and clinical research is warranted to validate present results and hypothesis.

Measurement of the tibial alignment after total knee replacement without the extramedullary cutting guide / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the accuracy and analysis of the influencing factors of the tibia prosthetic coronal alignment after total knee arthroplasty without tibia extramedullary cutting guide.@*METHODS@#In the study, 76 patients (96 knees) who had primary total knee arthroplasty in Peking University First Hospital from February 2012 to April 2016 were selected retrospectively. All of the cases were performed by the same experienced orthopedic surgeon team. The patients were divided into 2 groups randomly: tibia cutting without guide group and tibia cutting with extramedullary guide group. Lower extremity standard anterior and posterior X-ray films of the knees were taken before and after surgery, and the anatomical tibial angle (AT), the posterior slope angle (PSA) before and after surgery, the tibia component angle (TCA) were measured in the X-ray films. We also recorded the beginning and finishing time of the operation, the operation sequence of the day respectively at the same time. The data were analyzed by correlation analysis, t test and chi square test between the two groups.@*RESULTS@#The age, gender, body mass index, AT/PSA before the surgery and TCA/PSA after the surgery of the two groups were no significant differences (P>0.05). The rate of 90-TCA≥ 3° was 31.5% (17 knees) and 31% (12 knees) respectively, there were no significant differences (P=0.956) between the two groups. The postoperative TCA of two groups was not correlated with age, gender, body mass index (BMI), operation side (P>0.05), there was also no correlation between the postoperative TCA and the start time of the operation, the whole operation time, and the operation sequence of the day (P>0.05). The two groups were divided into subgroups according to 90-AT before the operation (0°≤90-AT<3°, 3°≤90-AT<5°, 5°≤90-AT<8°, 90-AT≥8°), and there was no difference among them. But we found there was a much higher rate of 90-TCA<3° in the group without cutting guide than the group with extramedullary guide when 90-AT≥8° before the surgery (the rates were 71.4 % and 42.9%, P<0.05).@*CONCLUSION@#There is no significant difference of the tibia prosthetic coronal alignment accuracy between the tibia cutting without guide and the traditional extramedullary guided bone cutting by experienced surgeons. Only if when patients already have suffered severe malformation of knee joint (90-AT≥8°) before the operation, tibia cutting without cutting guide is more effective to rectify the tibia prosthetic coronal alignment.