Comprehensive analysis of the protein phosphatase 2A regulatory subunit B56ε in pan-cancer and its role and mechanism in hepatocellular carcinoma.

BACKGROUND: B56ε is a regulatory subunit of the serine/threonine protein phosphatase 2A, which is abnormally expressed in tumors and regulates various tumor cell functions. At present, the application of B56ε in pan-cancer lacks a comprehensive analysis, and its role and mechanism in hepatocellular carcinoma (HCC) are still unclear. AIM: To analyze B56ε in pan-cancer, and explore its role and mechanism in HCC. METHODS: The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Profiling Interactive Analysis, and Tumor Immune Estimation Resource databases were used to analyze B56ε expression, prognostic mutations, somatic copy number alterations, and tumor immune characteristics in 33 tumors. The relationships between B56ε expression levels and drug sensitivity, immunotherapy, immune checkpoints, and human leukocyte antigen (HLA)-related genes were further analyzed. Gene Set Enrichment Analysis (GSEA) was performed to reveal the role of B56ε in HCC. The Cell Counting Kit-8, plate cloning, wound healing, and transwell assays were conducted to assess the effects of B56ε interference on the malignant behavior of HCC cells. RESULTS: In most tumors, B56ε expression was upregulated, and high B56ε expression was a risk factor for adrenocortical cancer, HCC, pancreatic adenocarcinoma, and pheochromocytoma and paraganglioma (all P < 0.05). B56ε expression levels were correlated with a variety of immune cells, such as T helper 17 cells, B cells, and macrophages. There was a positive correlation between B56ε expression levels with immune checkpoint genes and HLA-related genes (all P < 0.05). The expression of B56ε was negatively correlated with the sensitivity of most chemotherapy drugs, but a small number showed a positive correlation (all P < 0.05). GSEA analysis showed that B56ε expression was related to the cancer pathway, p53 downstream pathway, and interleukin-mediated signaling in HCC. Knockdown of B56ε expression in HCC cells inhibited the proliferation, migration, and invasion capacity of tumor cells. CONCLUSION: B56ε is associated with the microenvironment, immune evasion, and immune cell infiltration of multiple tumors. B56ε plays an important role in HCC progression, supporting it as a prognostic marker and potential therapeutic target for HCC.

Blood donor recruitment in Guangzhou, China, during the 2019 novel coronavirus (COVID-19) epidemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) epidemic affected blood collection in Guangzhou, China. STUDY DESIGN AND METHODS: This paper includes three studies. The observational study reported the trends of blood collection during the epidemic in Guangzhou, China. The cross-sectional survey investigated factors influencing blood donation during the COVID-19 epidemic, and a self-administered questionnaire was given to 1584 street whole blood donors (SWBDs) who donated during the epidemic. The randomized controlled trial involved 19 491 SWBDs who donated in 2019 but did not donate during the epidemic. Trial participants were randomly assigned to two intervention groups: Group 1 completed Questionnaire 1, which contained precautionary measures in response to COVID-19 and other messages about blood donation during the epidemic; Group 2 completed Questionnaire 2, which did not include this information. A control group did not receive any questionnaire. RESULTS: As measures were implemented, the number of blood donors increased accordingly. Both first-time and repeat SWBDs perceived the same level of blood need and donated blood because it would save lives. SWBDs who completed Questionnaire 1 expressed a greater intention to donate during the epidemic. Enabling blood donors to perceive a higher level of blood need and a lower level of COVID-19 infection risk related to blood donation mobilized experienced SWBDs to donate within 3 weeks. Intention-to-treat analyses and average-treatment-effect-on-the-treated estimations confirmed that Questionnaire 1 could motivate SWBDs to actually donate blood. CONCLUSION: Various measures could ease blood shortage during the COVID-19 epidemic. Administration of Questionnaire 1 could increase blood donations during the epidemic.

Effective methods for reactivating inactive blood donors: a stratified randomised controlled study.

BACKGROUND: Recruiting of sufficient numbers of donors of blood products is vital worldwide. In this study we assessed the efficacy and cost-effectiveness of telephone calls and SMS reminders for re-recruitment of inactive blood donors. METHODS: This single-centre, non-blinded, parallel randomised controlled trial in Guangzhou, China included 11,880 inactive blood donors whose last donation was between January 1 and June 30, 2014. The donors were randomly assigned to one of two intervention groups (telephone call or short message service [SMS] communications) or to a control group without intervention. SMS messages with altruistic appeal were adopted in the SMS group; in addition to altruistic appeal, reasons for deferral of blood donation were also asked in the telephone group. All participants were followed up for 1 year. The primary outcome was re-donation rate, and rates in different groups were compared by intention-to-treat (ITT) analysis and estimation of the average treatment effect on the treated (ATT). Secondary outcomes were the self-reported deterrents. Other outcomes included the re-donation interval, and the incremental cost-effectiveness ratio (ICER) of telephone calls and SMS reminders on re-recruitment. RESULTS: ITT analysis revealed no significant differences in the re-donation rate among the three groups. ATT estimations indicated that among compliers, telephone calls significantly increased re-donation compared to both SMS reminders and no intervention. Donor return behaviour was positively associated with receiving reminders successfully, being male, older age, and previous donation history. The SMS reminder prompted donors to return sooner than no reminder within 6 months, and according to ICER calculations, SMS reminders were more cost-effective than telephone calls. Donors reported time constraints as the most main causes of self-deferral in the telephone group, and altruistic appeal had a positive effect on these donors. CONCLUSIONS: Interventions to reactivate inactive blood donors can be effective, with telephone calls prompting more donors to return but at a greater cost than SMS messages. SMS reminder with altruistic appeal can urge donors to re-donate sooner within 6 months than no reminder. TRIAL REGISTRATION: NCT03366441 (Reactivation of Inactive Blood Donors). Retrospectively registered 4 December 2017.

Combined effects of six cytokine gene polymorphisms and SNP-SNP interactions on hepatocellular carcinoma risk in Southern Guangxi, China.

Cytokine gene single nucleotide polymorphisms (SNPs) are involved in the genesis and progression of hepatocellular carcinoma (HCC). We hypothesized that combined effects of cytokine gene SNPs and SNP-SNP interactions are associated with HCC risk. Six SNPs in cytokine genes (IL-2, IFN-γ, IL-1ß, IL-6, and IL-10) were genotyped in a study of 720 Chinese HCC cases and 784 cancer-free controls. Although none of these SNPs individually had a significant effect on the risk of HCC, we found that the combined effects of these six SNPs may contribute to HCC risk (OR=1.821, 95% CI=1.078-3.075). This risk was pronounced among smokers, drinkers, and hepatitis B virus carriers. A SNP-SNP interaction between IL-2-330 and IFN-γ-1615 was associated with an increased HCC risk (OR=1.078, 95% CI=1.022-1.136). In conclusion, combined effects of SNPs and SNP-SNP interactions in cytokine genes may contribute to HCC risk.

[Relationship between IL6 -572G/C polymorphism and hepatocellular carcinoma in men].

To study the relationship between the interleukin (IL)6 -572G/C polymorphism and risk of hepatocellular carcinoma (HCC) in men.A hospital-based case-control study was conducted with 500 male HCC patients without tumor history in other organs and 590 healthy male controls without history of tumors or chronic diseases. All HCC cases were diagnosed by histopathology. The controls were recruited from the Department of Orthopedic Trauma and Ophthalmology at the same hospital. The IL-6 promoter -572G/C polymorphism and its genotype variants were detected by real-time fluorescence quantitative PCR. The Chi-squared test and unconditional logistic regression analyses were applied to determine the risk of HCC among men carrying the different genotype variants.The frequencies of alleles and distribution of genotypes in the -572G/C loci were not significantly different between the HCC cases and controls (P more than 0.05). The Chi-squared test indicated that the polymorphisms of the loci were not associated with HCC in our male population. However, after adjusting by multivariate logistic regression, the odds ratio (OR) of HCC for the G allele (CG + GG genotypes) carriers was 1.31 (95% confidence interval (CI): 1.00 - 1.71) compared with the CC genotype. Among the male HBV carriers, the CG genotype increased HCC risk significantly (OR = 1.60, 95% CI: 1.14 - 2.24) compared with the CC genotype. A trend test indicated that HCC risk was significantly increased with the numbers of G alleles (P trend less than 0.05). Breslow-Day tests of homogeneity of the ORs indicated an interaction between hepatitis B virus (HBV) infection and polymorphisms of IL-6 (P less than 0.05). The synthetic odds ratio (OReg) of HBV infection and harboring a G allele was 5.95 (95% CI: 3.99-8.87), which represented a super multiplication interaction.Polymorphism of the IL-6 promoter -572 loci may be associated with HCC occurrence in men. Moreover, there is a super multiplication interaction for HCC risk between HBV infection and harboring the IL-6 G allele.

TNF-α -863 polymorphisms and the risk of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common type of highly malignant tumor. Guangxi is an area of China characterized by a high incidence of HCC. Previous epidemiological studies have found that chronic infection with hepatitis B virus (HBV) is one of the major etiological risk factors for HCC in China. With the increased understanding of the host immune response against HBV and the pathogenesis of the virus, at present, greater attention is being given to the immune response of cytokine genes, as polymorphisms may have a major impact on the course and outcome of HBV infection. In the present study, we genotyped tumor necrosis factor-α (TNF-α) rs1800629 (-308G/A), rs1800630 (-863C/A); interleukin-1B rs1143627 (-31T/C); and transforming growth factor ß1 (TGF-ß1) rs1800469 (-509C/T) in a hospital-based study of 772 HCC cases and 852 cancer-free controls. The distribution of the frequency of TNF-α rs1800630 sites of CC, CA, AA were 65.67, 27.46 and 6.87% in the case group, respectively, as compared with 67.02, 29.58 and 3.40% in the controls, all with a statistical significance (P<0.05). The logistic regression analysis revealed that the variant rs1800630 AA genotypes were associated with a significantly increasing risk of HCC (OR=2.058, 95% CI 1.289-3.287), compared with the wild-type rs1800630 CC. Further stratified analyses showed that after stratification for history of alcohol drinking, in a subgroup of individuals without a history of drinking, the HCC risk in the group with the TNF-α rs1800630 A allele was 1.839 times higher than that in the group with TNF-α rs1800630 C (P<0.010). These findings suggest that TNF-α rs1800630 may contribute to the risk of HCC, however, these data require further validation.

[Study on the relationship between single-nucleotide polymorphisms in IL-6, IL-10 genes and HBV-related hepatocellular carcinoma].

OBJECTIVE: To investigate the association between single nucleotide polymorphisms (SNPs) in cytokine IL-6, IL-10 genes and HBV-related hepatocellular carcinoma (HCC). METHODS: A hospital-based case-control study was conducted in 381 cases with HBV-related HCC, 340 HBsAg carriers and 359 non-tumor controls. Genotypes of -572 site of IL-6 gene and -819, -592 sites of IL-10 gene were determined by real-time polymorphism chain reaction. Unconditional logistic regression was used to estimate the odds ratios (ORs) and 95 confidence intervals (CIs). RESULTS: For the G/C alleles of -572 loci on IL-6 gene, there were significant differences between the three groups (P < 0.05). Compared with CC genotype, GG genotype increased the risk of HBV infection (OR = 2.171, 95%CI: 1.068 - 4.415), but did not seem to be associated with HCC. For the alleles of -819 and -592 site of IL-10 gene, there were significant differences between the three groups (P < 0.05). Compared with CC genotype, TT genotype increased the risks of both HCC (OR = 2.791, 95%CI: 1.326 - 5.874), and HCC in HBsAg carriers (OR = 3.522, 95%CI: 1.707 - 7.266). When compared with CC genotype on -592 site, the AA genotype reduced the risk of both HCC (OR = 0.389, 95%CI: 0.173 - 0.875), and HCC in HBsAg carriers (OR = 0.336, 95%CI: 0.154 - 0.734). CONCLUSION: The SNPs in -572 site of IL-6 gene might be associated with the risk of HBV infection. The SNPs in -819 site of IL-10 gene increased the risk of HCC, but -592 site of IL-10 gene decreased the risk of HCC.

[Serum sCD40L detection for risk evaluation of acute coronary syndromes].

OBJECTIVE: To investigate the value of serum soluble CD40 ligand (sCD40L) detection in risk evaluation of acute coronary syndromes (ACS). METHODS: This study involved 200 patients with established diagnosis of ACS, with death or nonfatal myocardial infarction as the end point of observation during the 6-month-long follow-up. Blood samples were obtained from the patients within the initial 72 h of ACS onset, and the levels of sCD40L and C-reactive protein (CRP) were determined with enzyme-linked immunosorbent assay (ELISA). Cardiac troponin I (cTnI) measurement was performed using chemiluminescent immunoassay. RESULTS: Of the 200 patients, 108 had serum sCD40L levels higher than 5.0 microg/L, and the levels of sCD40L, CRP and cTnI were found to significantly correlate with ACS. CONCLUSION: Independent detection of serum sCD40L, CRP and cTnI can help predict the risks of ACS, and their combined measurement may increase the sensitivity of the risk prediction and provide new cardiac makers to replace the cardiac enzymes for laboratory diagnosis and risk evaluation of cardiovascular events.

[Effect of percutaneous coronary intervention on QT dispersion and its clinical implication in patients with acute myocardial infarction].

OBJECTIVE: To observe the effects of percutaneous coronary intervention (PCI) on QT dispersion (QTd) and explore its clinical significance in patients with acute myocardial infarction (AMI). METHODS: The electrocardiograms recorded before and one day after PCI were analyzed in 138 patients with AMI. The duration from the onset of AMI to PCI operation was less than 6 h in 72 patients and 6 to 12 h in the other patients. All the patients underwent emergency percutaneous transluminal coronary angioplasty and subsequent coronary stenting. QT intervals, QTd, and heart rate-corrected QT intervals (QTc) and QTd (QTcd) were measured and calculated. RESULTS: In both patient groups receiving PCI with delay shorter and longer than 6 h after AMI, QT and QTc after PCI were not significantly different from that before PCI, but the QTd and QTcd were remarkably decreased after PCI (all the P <0.01). Moreover, the QTd and QTcd in the patients with delay of PCI less than 6 h were significantly shorter than those in patients the with greater-than-6-hour delay (P<0.05), and the inhospital mortality was 4.2% and 7.6% in the two groups, respectively (P=0.394). CONCLUSION: Successful PCI may notably reduce QTd in the patients with AMI, whose earlier performance usually produces better effects.

[Changes in proinflammatory cytokines and immune function of subeschar tissue fluid during early stage after severe burn].

OBJECTIVE: To evaluate the inflammatory response and immune function of subeschar tissue fluid (STF) in early stage of severe burn. METHODS: Eight patients were observed and samples from blood as well as STF were collected at 16, 24, 32, 40, 48 hours following burn to measure white blood cell (WBC) counts, levels of immunoglobin (IgA, IgG, IgM), complement (C3, C4) values as well as proinflammatory cytokines as tumor necrosis factor-alpha (TNF-alpha), interleukin-6(IL-6) and IL-8. In addition, twenty Balb-c mice were used for the lethal experiment by STF collected at 48 hours after burn. RESULTS: The levels of IgA, IgG, IgM in STF were about half of those in the blood samples (all P<0.01). The WBC counts in STF were 1/100 time of that in the blood (all P<0.01). The contents of TNF-alpha, IL-6 and IL-8 in STF were comparable with those in the blood (P>0.05). Following STF challenge, none of the mice died during 7-day observation period. CONCLUSION: The cells and large molecules seems to be more difficult to enter STF compared with small molecules. No marked local inflammatory response occurs in STF during early stage of severe burn, and STF challenge has no lethal effect. The low WBC counts and low immunoglobin as well as complement levels imply the limited effect of STF on local infection, and effective antibiotics should be timely used after major burn.

[Clinical evaluation of the postburn retention and the metabolism of Imipenem in the third space].

OBJECTIVE: To explore the half life and retention of Imipenem in the third space. METHODS: Eight severely burned patients and eight healthy volunteers were enrolled as the burn group (B) and normal control group (C), respectively. HPLC (high performance liquid chromatography) was employed to determine the contents of Imipenem in the plasma, subeschar tissue fluid (STF) and the changes in its pharmacokinetics. Furthermore, the Imipenem content in the third space was calculated according to the systemic edema degree. RESULTS: The half life of Imipenem in STF (2.53 h) was longer than that in plasma (1.73 h), P < 0.05). The Imipenem content in STF increased gradually along with the lapse of time after repeated intravenous infusion of Imipenem, and at the same the total content of imipenem was increased significantly in the third space. CONCLUSION: There was antibiotic retention in the third space after severe burn injury, and a prolonged action of the drug could be expected when the drug re-entered the blood stream.