Comprehensive analysis of the potential pathogenesis of COVID-19 infection and liver cancer.

BACKGROUND: A growing number of clinical examples suggest that coronavirus disease 2019 (COVID-19) appears to have an impact on the treatment of patients with liver cancer compared to the normal population, and the prevalence of COVID-19 is significantly higher in patients with liver cancer. However, this mechanism of action has not been clarified. AIM: To investigate the disease relevance of COVID-19 in liver cancer. METHODS: Gene sets for COVID-19 (GSE180226) and liver cancer (GSE87630) were obtained from the Gene Expression Omnibus database. After identifying the common differentially expressed genes (DEGs) of COVID-19 and liver cancer, functional enrichment analysis, protein-protein interaction network construction and screening and analysis of hub genes were performed. Subsequently, the validation of the differential expression of hub genes in the disease was performed and the regulatory network of transcription factors and hub genes was constructed. RESULTS: Of 518 common DEGs were obtained by screening for functional analysis. Fifteen hub genes including aurora kinase B, cyclin B2, cell division cycle 20, cell division cycle associated 8, nucleolar and spindle associated protein 1, etc., were further identified from DEGs using the "cytoHubba" plugin. Functional enrichment analysis of hub genes showed that these hub genes are associated with P53 signalling pathway regulation, cell cycle and other functions, and they may serve as potential molecular markers for COVID-19 and liver cancer. Finally, we selected 10 of the hub genes for in vitro expression validation in liver cancer cells. CONCLUSION: Our study reveals a common pathogenesis of liver cancer and COVID-19. These common pathways and key genes may provide new ideas for further mechanistic studies.

Analysis of the potential biological value of pyruvate dehydrogenase E1 subunit ß in human cancer.

BACKGROUND: The pyruvate dehydrogenase E1 subunit ß (PDHB) gene which regulates energy metabolism is located in mitochondria. However, few studies have elucidated the role and mechanism of PDHB in different cancers. AIM: To comprehensive pan-cancer analysis of PDHB was performed based on bioinformatics approaches to explore its tumor diagnostic and prognostic value and tumor immune relevance in cancer. In vitro experiments were performed to examine the biological regulation of PDHB in liver cancer. METHODS: Pan-cancer data related to PDHB were obtained from the Cancer Genome Atlas (TCGA) database. Analysis of the gene expression profiles of PDHB was based on TCGA and Genotype Tissue Expression Dataset databases. Cox regression analysis and Kaplan-Meier methods were used to assess the correlation between PDHB expression and survival prognosis in cancer patients. The correlation between PDHB and receiver operating characteristic diagnostic curve, clinicopathological staging, somatic mutation, tumor mutation burden (TMB), microsatellite instability (MSI), DNA methylation, and drug susceptibility in pan-cancer was also analyzed. Various algorithms were used to analyze the correlation between PDHB and immune cell infiltration and tumor chemotaxis environment, as well as the co-expression analysis of PDHB and immune checkpoint (ICP) genes. The expression and functional phenotype of PDHB in single tumor cells were studied by single-cell sequencing, and the functional enrichment analysis of PDHB-related genes was performed. The study also validated the level of mRNA or protein expression of PDHB in several cancers. Finally, in vitro experiments verified the regulatory effect of PDHB on the proliferation, migration, and invasion of liver cancer. RESULTS: PDHB was significantly and differently expressed in most cancers. PDHB was significantly associated with prognosis in patients with a wide range of cancers, including kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, breast invasive carcinoma, and brain lower grade glioma. In some cancers, PDHB expression was clearly associated with gene mutations, clinicopathological stages, and expression of TMB, MSI, and ICP genes. The expression of PDHB was closely related to the infiltration of multiple immune cells in the immune microenvironment and the regulation of tumor chemotaxis environment. In addition, single-cell sequencing results showed that PDHB correlated with different biological phenotypes of multiple cancer single cells. This study further demonstrated that down-regulation of PDHB expression inhibited the proliferation, migration, and invasion functions of hepatoma cells. CONCLUSION: As a member of pan-cancer, PDHB may be a novel cancer marker with potential value in diagnosing cancer, predicting prognosis, and in targeted therapy.

Safety and efficacy of thalidomide in patients with transfusion-dependent ß-thalassemia: a randomized clinical trial.

Thalidomide induces γ-globin expression in erythroid progenitor cells, but its efficacy on patients with transfusion-dependent ß-thalassemia (TDT) remains unclear. In this phase 2, multi-center, randomized, double-blind clinical trial, we aimed to determine the safety and efficacy of thalidomide in TDT patients. A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks, followed by an extension phase of at least 36 weeks. The primary endpoint was the change of hemoglobin (Hb) level in the patients. The secondary endpoints included the red blood cell (RBC) units transfused and adverse effects. In the placebo-controlled period, Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0 (range, 2.5 to 37.5) g/L, whereas Hb in patients treated with placebo did not significantly change. Within the 12 weeks, the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4 ± 5.0 U and 10.3 ± 6.4 U, respectively (P < 0.001). Adverse events of drowsiness, dizziness, fatigue, pyrexia, sore throat, and rash were more common with thalidomide than placebo. In the extension phase, treatment with thalidomide for 24 weeks resulted in a sustainable increase in Hb concentrations which reached 104.9 ± 19.0 g/L, without blood transfusion. Significant increase in Hb concentration and reduction in RBC transfusions were associated with non ß0/ß0 and HBS1L-MYB (rs9399137 C/T, C/C; rs4895441 A/G, G/G) genotypes. These results demonstrated that thalidomide is effective in patients with TDT.

[Influence of femoral neck area on larger anteversion angle of lag screw guide pin initial placement in proximal femoral intramedullary nail fixation].

OBJECTIVE: To invstigate the influence of femoral neck area on larger anteversion angle of lag screw guide pin initial placement in proximal femoral intertrochanteric fracture treated with intramedullary nail. METHODS: From June 2014 to June 2016, 60 patients with femoral intertrochanteric fractures were treated with intramedullary nail, including 27 males and 33 females with an average age of 75 years old ranging from 49 to 88 years old. The lateral images of femoral neck were divided into areas during operation. The anteversion angle of lag screw guide pin of proximal femoral nail was observed at the time of initial insertion. The incidence of normal and larger was counted and the angle index of influencing factors was recorded. RESULTS: Among 60 patients, the screw guide pins of 23 cases were in the central region of the femoral neck and the anteversion angle was normal;screw guide pins of 37 cases were in the front area of the femoral neck, leading to larger anteversion angle. The single factor analysis showed that the independent variables influence factors of larger anteversion were internal collection of the affected limb, internal rotation of the affected limb, hip elevation and screw guide pin level(P<0.05). The multi-factor regression analysis showed that the anteversion angle larger was significantly related to the internal rotation of the affected limb and screw guide pin level, and the screw guide pin level was the most relevant(P=0.030). CONCLUSIONS: The internal rotation of the affected limb and screw guide pin level may affect the anteversion angle of femoral neck when lag screw guide pin initial insertion, cause it to be too large and the screw guide pin level is the main influencing factor.

[Narcotrend for monitoring the anesthetic depth during endotracheal intubation in sevoflurane anesthesia].

OBJECTIVE: To study the feasibility of using Narcotrend (NCT) in monitoring the anesthetic depth during endotracheal intubation in sevoflurane anesthesia. METHODS: Thirty ASA I-II patients (aged 20-49 years) undergoing gynecologic surgery under general anesthesia with tracheal intubation were randomized into sevoflurane group (n=15) and sevoflurane plus rocuronium group (n=15). In the former group, anesthesia was induced with sevoflurane at the primary concentration of 8% till the final end expiratory concentration reaching 2 MAC(minimum alveolar concentration) for 3 min, followed then by tracheal intubation and further observation of the indicators for another 3 min. The patients in sevoflurane plus rocuronium group received identical anesthesia procedures except for the administration of intravenous injection of rocuronium (0.6 mg/kg) after the loss of eyelash reflex. The NCT, BIS and hemodynamics were recorded during the process. RESULTS: No significant differences were noted in NCT, bispectral index (BIS), MAP and heart rate before tracheal intubation between the two groups (P>0.05). The NCT and BIS increased significantly after tracheal intubation in sevoflurane group (P<0.05), but remained below 60. No significant changes in NCT and BIS occurred during intubation in sevoflurane plus rocuronium group (P>0.05). The mean arterial pressure (MAP) and heart rate were significantly increased in both groups after tracheal intubation in comparison with those before tracheal intubation (P<0.05), but the increment in sevoflurane group was significantly greater (P<0.05). CONCLUSION: NCT may reflect the changes of the anesthetic depth resulting from the nociceptive stimulus of tracheal intubation in sevoflurane- induced anesthesia. NCT and BIS can not serve such a purpose in combined anesthesia with sevoflurane and rocuronium.

[Correlation between the Narcotrend index, the cerebral state index and the predicted effect site concentration during different state of consciousness in elderly patients with target controlled infusion of propofol].

OBJECTIVE: To study the correlation between the Narcotrend index, cerebral state index and predicted effect site concentration during different state of consciousness in the absence of surgery in elderly patients with target controlled infusion of propofol. METHODS: Twenty patients aged from 65-75 years categorized as ASA class I - II who were scheduled to undergo general surgery under general anesthesia with target controlled infusion of propofol were recruited. During the target controlled infusion of propofol, the propofol infusion was set at an initial effect site concentration of 0.5 mg/L and increased by 0.5 mg /L every 5 min until the modified observer's assessment of alertness / sedation scale (OAA/S) values of zero. The predicted effect site concentration of propofol, the values of CSI and NCT were recorded and the sedation level was examined by the modified OAA/S every 20 s. The predicted effect site concentrations of propofol in target controlled infusion (TCI) system were recorded when they increased by more than 0.1 mg/L. The predicted effect site concentrations of propofol and the values of NCT and CSI at LVC and LOC of the patients were recorded. RESULTS: There was a good linear correlation between NCT and the predicted effect site concentration of propofol (R2 = 0. 867, P < 0.01), as well as that between CSI and the predicted effect site concentration of propofol (R2 = 0.893, P < 0.01). The predicted effect site concentrations of propofol at LVC was (1.56 +/- 0.13) mg/L while the values of NCT was 74.00 +/- 4.69 and CSI 69.82 +/- 5.47. The predicted effect site concentrations of propofol at LOC was (2.15 +/- 0.27) mg/L while the values of NCT and CSI were 63.30 +/- 7.50 and 58.78 +/- 6.90 respectively. All of the values of NCT, CSI and the predicted effect site concentrations had a good linear correlation with OAA/S. There was a negative correlation between OAA/S and the predicted effect site concentration. At the same time, there was a positive correlation between OAA/S and NCT as well as that between OAA/S and CSI. And the correlation coefficients were - 0.968, 0.938, 0.940 respectively (P < 0.01). The values of NCT were higher significantly than that of CSI in different degree of LOC (P < 0.01). CONCLUSION: During elder people's target controlled infusion of propofol, LVC and LOC occur within a definite range of predicted effect site concentrations. There is a good linear correlation between NCT, CSI and the predicted effect site concentrations of propofol. For the elders, both NCT and CSI reflect the sedation level of propofol. Although there is a significant correlation between NCT and CSI, a deviation does exist in a certain range. Therefore a simple 1:1 transfer from NCT to CSI is inadequate.