[Application of esmolol in severe hand, foot, and mouth disease].

OBJECTIVE: To study the clinical effect and mechanism of action of esmolol in the treatment of severe hand, foot, and mouth disease (HFMD). METHODS: A prospective randomized controlled trial was performed. A total of 102 children with severe HFMD were enrolled in the study and were randomly divided into conventional treatment and esmolol treatment groups (n=51 each). The children in the conventional treatment group were given conventional treatment according to the guidelines for the diagnosis and treatment of HFMD. Those in the esmolol treatment group were given esmolol in addition to the conventional treatment. The heart rate (HR), systolic blood pressure (SBP), and respiratory rate (RR) were continuously monitored for all children. Blood samples were collected from all children before treatment and 1, 3, and 5 days after treatment to measure the levels of norepinephrine (NE), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and nuclear factor-kappa B (NF-κB) p65 in mononuclear cells. Serum levels of myocardial enzymes and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured before treatment and after 5 days of treatment. RESULTS: There were no significant differences in HR, SBP, RR, NE, TNF-α, IL-6, NF-κB p65, serum myocardial enzymes, and NT-proBNP before treatment between the conventional treatment and esmolol treatment groups. Both groups had significant reductions in these parameters at each time point (P<0.05). Compared with the conventional treatment group, the esmolol treatment group had significant improvements in the above parameters after 1 and 3 days of treatment (P<0.05). After 5 days of treatment, the esmolol treatment group had significant improvements in serum levels of myocardial enzymes and NT-proBNP compared with the conventional treatment group (P<0.05). CONCLUSIONS: Early application of esmolol can effectively stabilize the vital signs of the children with severe HFMD. Its mechanism of action may be related to reducing serum catecholamine concentration, alleviating myocardial damage, improving cardiac function, and reducing inflammatory response.

[Expression of vasoactive intestinal peptide in peripheral blood of children with hand, foot and mouth disease].

OBJECTIVE: To investigate the expression of vasoactive intestinal peptide (VIP) in peripheral blood of children with hand, foot and mouth disease and its significance. METHODS: According to the condition of the disease, 86 children with hand, foot and mouth disease were classified into phase 1 group (19 children) and phase 2 group (67 children). ELISA was used to measure the concentrations of plasma VIP, interferon-γ (IFN-γ), and interleukin-4 (IL-4) in peripheral blood. Flow cytometry was used to measure CD3+, CD4+, and CD8+ T lymphocyte subsets. RT-PCR was used for qualitative detection of enterovirus 71 (EV71) RNA in stool. RESULTS: Compared with the phase 1 group, the phase 2 group had a significantly higher positive rate of EV71-RNA (P<0.05) and significantly higher serum levels of IgG, IgA, IgM, and C3 (P<0.05). The phase 2 group had significantly lower proportions of peripheral CD3+, CD4+, and CD8+ T lymphocyte subsets than the phase 1 group (P<0.05), as well as significantly lower proportion of peripheral B cells and CD4+/CD8+ ratio than the phase 1 group (P<0.05). The phase 2 group also had a significantly lower concentration of VIP in peripheral blood than the phase 1 group (P<0.05). In the 86 children with hand, foot and mouth disease, the concentration of VIP in peripheral blood was positively correlated with the proportion of CD4+ T lymphocyte subset and CD4+/CD8+ ratio (r=0.533 and 0.532 respectively; P<0.05). CONCLUSIONS: VIP may be an important marker of the severity of hand, foot and mouth disease.

Differential effects of paraoxonase 1 (PON1) polymorphisms on cancer risk: evidence from 25 published studies.

Paraoxonase is an HDL-associated enzyme that plays a preventive role against oxidative stress, which is thought to contribute to cancer development. PON1 activity varies widely among individuals, which is in part related to two common nonsynonymous polymorphisms in the PON1 gene (Q192R and L55M). The polymorphisms in PON1 have been implicated in cancer risk. However, results from the studies to date have been conflicting. To clarify the association, a meta-analysis was performed for 7,073 cases and 9,520 controls from 25 published case-control studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. Significant associations between PON1-L55M but not Q192R polymorphism and total cancer were observed from all the comparisons. In stratified analyses, PON1-55M allele was a risk factor for breast cancer. Similarly, increased risk was observed for prostate cancer (OR = 1.18, 95% CI: 1.01-1.36, P (heterogeneity) = 0.260) and Caucasian population (OR = 1.18, 95% CI: 1.02-1.38, P (heterogeneity) = 0.1) of the LM genotype, compared with the LL genotype. For PON1-Q192R polymorphism, PON1-192R allele was a decreased risk factor for cancer in the Asian group (RR vs QQ: OR = 0.61, 95% CI: 0.38-0.98, P (heterogeneity) = 0.268; QR vs QQ: OR = 0.71, 95% CI: 0.52-0.96, P (heterogeneity) = 0.130; RR + QR vs QQ: OR = 0.71, 95% CI: 0.53-0.95, P (heterogeneity) = 0.135). Although some modest bias could not be eliminated, this meta-analysis suggests that the PON1-55M allele is a risk factor for the development of cancer, in particular for breast cancer. Future studies with larger sample sizes are warranted to further evaluate these associations.

Ratios of CD64 expressed on neutrophils, monocytes, and lymphocytes may be a novel method for diagnosis of neonatal sepsis.

INTRODUCTION: Neutrophil CD64 expression has been demonstrated as an improved diagnostic marker of infection and sepsis. The purpose of this study was to develop a new method to evaluate neutrophil CD64 expression for diagnosis of neonatal sepsis. METHODOLOGY: Eighty neonates with neonatal sepsis (21 culture positive, 59 negative) were enrolled in this prospective study along with 19 neonates with no symptoms or signs of infection as controls. Expressions of CD64 on monocytes, lymphocytes, and neutrophils were evaluated with flow cytometry (FCM). Ratios were calculated with these levels of CD64 expression. Blood culture and other laboratory exams were done at the same time for the diagnosis of neonatal sepsis. Results were compared between the neonatal sepsis and control groups. RESULTS: CD64 ratios showed significant difference between the groups (p < 0.01). Receiver operating curve (ROC) analysis showed that the CD64 ratios possessed high sensitivity (90%) and specificity (89.5%) in neonatal sepsis identification. CONCLUSIONS: The novel CD64 evaluation method, CD64 ratio, can be used as a supplementary method for diagnosis of neonatal sepsis.

Methionine synthase reductase A66G polymorphism and leukemia risk: evidence from published studies.

Methionine synthase reductase (MTRR) is required for the reductive methylation of cobalamin, which is the functional cofactorial form of methionine synthase (MS) in the remethylation of homocysteine to methionine. The MTRR A66G (rs1801394) polymorphism is found to be associated with decreased enzyme affinity for MTR, the gene that encodes MS, and has been widely investigated for cancer risk, including leukemia. However, the conclusions of epidemiological studies have always been contradictory. To further clarify the association of MTRR A66G polymorphism with the risk of leukemia, this meta-analysis was performed for 2913 cases and 4764 controls. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. Pooled ORs were determined for the co-dominant model (GG vs. AA, AG vs. AA), dominant model (GG + AG vs. AA) and recessive model (GG vs. AA+ AG), respectively. No significant associations were found for all comparisons in the overall pooled analysis. However, the results of stratified analyses revealed that MTRR A66G GG genotype was associated with decreased leukemia risk in the Caucasian population, in children and for acute lymphoblastic leukemia (ALL). In contrast, increased risk was observed in the Asian population and for acute myeloid leukemia (AML). This meta-analysis suggests that MTRR A66G GG is associated with decreased risk of leukemia in a Caucasian population and in children, especially for ALL.