Individualized Use of 6-Mercaptopurine in Chinese Children with ALL: A Multicenter Randomized Controlled Trial.

Continuous 6-mercaptopurine (6-MP) dose titration is necessary because of its narrow therapeutic index and frequently encountered dose-limiting hematopoietic toxicity. However, evidence-based guidelines for gene-based 6-MP dosing have not been established for Chinese children with acute lymphoblastic leukemia (ALL). This multicenter, randomized, open-label, active-controlled clinical trial randomly assigned Chinese children with low- or intermediate-risk ALL in a 1:1 ratio to receive TPMT-NUDT15 gene-based dosing of 6-MP (N = 44, 10 to 50 mg/m2 /day) or standard dosing (N = 44, 50 mg/m2 /day) during maintenance therapy. The primary end point was the incidence of 6-MP myelosuppression in both groups. Secondary end points included frequencies of 6-MP hepatotoxicity, duration of myelosuppression and leukopenia, event-free survival, and steady-state concentrations of active metabolites (6-thioguaninenucleotides and 6-methylmercaptopurine nucleotides) in erythrocytes. A 2.2-fold decrease in myelosuppression, the primary end point, was observed in the gene-based-dose group using ~ 50% of the standard initial 6-MP dose (odds ratio, 0.26, 95% confidence interval, 0.11 to 0.64, P = 0.003). Patients in the gene-based-dose group had a significantly lower risk of developing thiopurine-induced myelosuppression and leukopenia (P = 0.015 and P = 0.022, respectively). No significant differences were observed in the secondary end points of the incidence of hepatotoxicity and steady-state concentrations of active metabolites in erythrocytes between the two groups. TPMT- and NUDT15-based dosing of 6-MP will significantly contribute toward further reducing the incidence of leukopenia in Chinese children with ALL. This trial is registered at www.clinicaltrial.gov as #NCT04228393.

CXCR4 enhances the inhibitory effects of bone mesenchymal stem cells on lung cell apoptosis in a rat model of smoking-induced COPD.

Chronic obstructive pulmonary disease is the 3rd leading cause of death worldwide, and the available treatments are unsatisfactory, resulting in a major economic burden. As cellular therapy is commonly used for lung disease, we investigated a treatment with CXCR4-overexpressing BMSCs in a COPD model. We extracted and purified Bone marrow mesenchymal stem cells (BMSCs) from SD rats. COPD apoptosis model was established by cigarette smoke exposure. BMSCs (1 × 106 cells per injection)were transplanted in vivo twice a month during model establishment, and alveolar rupture in the lung was assessed. Lung cell apoptosis was assessed by terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) analysis, and the concentrations of apoptotic proteins in the lungs were detected by Western blotting. We successfully isolated BMSCs and established CXCR4-overexpressing BMSCs. qRT‒PCR and Western blotting detection both reveal that CXCR4 mRNA level and protein both significantly higher expression in CXCR4-BMSCs than the pBABE-BMSCs. Continuous cigarette smoke exposure caused alveolar septal rupture: In the model group, the alveolar mean linear intercept in the first month was significantly lower than that in the third month (p < 0.05). In the third month, the alveolar mean linear intercept values of the control and CXCR4-BMSC groups were lower than those of the model group (control group p < 0.01, CXCR4-BMSC group p < 0.05), and TUNEL staining revealed that the apoptosis rates of the control and CXCR4-BMSC groups were significantly lower than those of the model group (p < 0.01). Furthermore, the levels of the apoptotic proteins cleaved caspase-8, cleaved caspase-3 and cleaved PARP-1 were higher in the model group than in the control group (p < 0.05) and significantly lower in the CXCR4-BMSC group than in the model group (p < 0.05). The transplantation of CXCR4-overexpressing BMSCs during COPD model generation significantly inhibited apoptosis via the extrinsic apoptosis pathway. CXCR4 enhances the inhibitory effects of bone mesenchymal stem cells on lung cell apoptosis in a rat model of smoking-induced COPD.

The General Self-Efficacy Scale in a population planned for bariatric surgery in Sweden: a psychometric evaluation study.

OBJECTIVES: This study psychometrically evaluated General Self-Efficacy (GSE) Scale in patients planned for bariatric surgery in Sweden. DESIGN: A cross-sectional psychometric study. The psychometric evaluation was guided by the COnsensus-based Standards for the selection of health status Measurement Instruments checklist for health-related reported-patient outcomes. SETTING: Three bariatric centres in Sweden. PARTICIPANTS: Adult patients≥18 years old scheduled for primary bariatric surgery (with sleeve gastrectomy or Roux-en-Y gastric bypass). PRIMARY AND SECONDARY MEASURES: Psychometric properties of the GSE. RESULTS: In total, 704 patients were included in the analysis. Mean values for GSE items were 2.9-3.4 and the mean GSE sum score was 31.4 (SD 4.7). There were no floor or ceiling effects. Cronbach's alpha was 0.89. Men reported a higher mean GSE than did women, that is, 31.2 (SD 4.8) for women versus 32.1 (SD 4.3) for men, p=0.03. Correlation coefficients were weak or negligible: GSE and mental component summary score of 36-Item Short Form Health Survey (SF-36)/RAND 36, r=0.18 (p<0.00); GSE and physical component summary score of SF-36/RAND 36, r=0.07 (p=0.138); GSE and obesity-related problem scale r=-0.15 (p=0.001) and GSE and level of education, r=0.04 (p=0.35). Confirmatory factor analysis indicated a one-factor construct with a satisfactory goodness of fit, that is, Comparative Fit Index=0.927, root mean square error of approximation=0.092 and standardised root mean square residual=0.045. The factor GSE explained almost half or over half of the variance of each item (0.45-0.75, p-values<0.001). CONCLUSIONS: The GSE scale is a valid and reliable scale that can be used to assess general self-efficacy in patients undergoing bariatric surgery.

Hypothesis testing in multivariate normal models with block circular covariance structures.

In this article, we address the problem of simultaneous testing hypothesis about mean and covariance matrix for repeated measures data when both the mean vector and covariance matrix are patterned. In particular, tests about the mean vector under block circular and doubly exchangeable covariance structures have been considered. The null distributions are established for the corresponding likelihood ratio test statistics, and expressions for the exact or near-exact probability density and cumulative distribution functions are obtained. The application of the results is illustrated by both a simulation study and a real-life data example.

Validity and reliability of the Swedish Functional Health Literacy scale and the Swedish Communicative and Critical Health Literacy scale in patients undergoing bariatric surgery in Sweden: a prospective psychometric evaluation study.

OBJECTIVES: The aim was to psychometrically test and evaluate the Swedish functional health literacy scale and the Swedish communicative and critical health literacy scale in patients undergoing bariatric surgery. DESIGN: A prospective cross-sectional psychometric study. SETTING: Patients from three bariatric centres in Sweden were consecutively included in this study. PARTICIPANTS: A total of 704 patients undergoing bariatric surgery filled in the questionnaires preoperatively. Inclusion criteria were scheduled for primary bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy) and greater than 17 years, proficiency in Swedish. PRIMARY AND SECONDARY MEASURES: Psychometric outcomes of the Swedish Functional Health Literacy scale and the Swedish Communicative and Critical Health Literacy scale. RESULTS: There was a higher proportion of females (74.4%, n=523) to males (25.6%, n=180). The mean age was 42 years (SD 11.5). Limited functional health literacy and limited communicative and critical health literacy (including both inadequate and problematic health literacy) was reported in 55% (n=390) and 40% (n=285), respectively. Cronbach alpha for the Swedish Functional Health Literacy scale was α=0.86 and for the Swedish Communicative and Critical Health Literacy scale, α=0.87. Construct validity showed weak to negative correlations between the Swedish Functional Health Literacy scale and income, education and SF-36/RAND36 summary scores. Confirmatory factor analysis showed a one-factor solution for the Swedish Functional Health Literacy scale and a two-factor solution for the Swedish Communicative and Critical Health Literacy scale. CONCLUSIONS: The Swedish Functional Health Literacy scale and the Swedish Communicative and Critical Health Literacy scale are valid and reliable to use for patients undergoing bariatric surgery in a Swedish context. Measuring dimensions of health literacy can be used as a guide for the development of health literacy friendly patient information in patients undergoing bariatric surgery.

A novel epidermal growth factor receptor inhibitor for treating lung cancer.

To investigate the effects of a novel synthetic epidermal growth factor receptor inhibitor, COMPOUND7809, on the inhibition of lung cancer growth in vitro and the underlying mechanisms, we treated three lung tumor cell lines (A549, SK-LU-1, and NCI-H23) with COMPOUND7809 and a Food and Drug Administration-approved epidermal growth factor receptor inhibitor gefitinib. Then, we examined cell growth in a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell survival in a Cell Counting Kit-8 assay, and cell apoptosis by Annexin V flow cytometry in the presence of fluorouracil. We found that compared to gefitinib, COMPOUND7809 inhibited cell growth more potentially and induced more cell death in the presence of fluorouracil. Thus, our study demonstrates that COMPOUND7809 may be a promising epidermal growth factor receptor inhibitor for human lung cancer therapy.

Association of p73 G4C14-to-A4T14 polymorphism with lung cancer risk.

Conflicting results were implicated in both single case-control studies and meta-analyses of the correlation between p73 G4C14-to-A4T14 polymorphism and lung cancer risk. We designed this study to further assess the association by meta-analysis. A meta-analysis was performed based on five case-control studies (5,467 subjects) retrieved from PubMed and Embase. Odds ratios (ORs) with 95 % confidence intervals (CIs) were measured for the association using the models of random effects and fixed effects. The results showed no evidence between p73 G4C14-to-A4T14 polymorphism and lung cancer risk in any genetic model (allele model: OR, 1.06, 95 % CI, 0.89-1.26; homozygote genotypes: OR, 1.18, 95 % CI, 0.80-1.73; heterozygote genotypes: OR, 1.04, 95 % CI, 0.89-1.23; dominant model: OR, 1.05, 95 % CI, 0.89-1.24; recessive model: OR, 1.17, 95 % CI, 0.93-1.47). Subgroup analyses according to ethnicity, however, detected significant association in Caucasian population. Our study provides evidence that p73 G4C14-to-A4T14 polymorphism may play a major role in susceptibility to lung cancer in Caucasians.