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Background: Congenital cytomegalovirus (cCMV) infection can lead to a range of adverse outcomes. The majority of cCMV neonates with clinical symptoms are infected postnatally; however, established cases of intrauterine infection are uncommon, resulting in a paucity of reports on clinical findings and lymphocytes expression in CMV-infected neonates. Case presentation: We followed a neonate with cCMV infection from the onset of hospitalization to several months of follow-up. This infant was intrauterine CMV-positive in the amniotic fluid of the mother at 21 weeks' gestation and received intravenous ganciclovir infusion and sequential oral valganciclovir after birth. The typical clinical signs manifested in the nervous system, liver, and peripheral blood and were documented during the hospitalizaion period and up to the follow-up visit. Flow cytometry was employed to examine the expression of T cells, their subsets, and the associated cytokines in peripheral blood samples at various time points. The flow data for the cCMV neonate were compared with those of the controls at each time point. Following treatment, clinical symptoms improved and the infant became CMV negative. However, developmental delays occurred later in life. The proportion of CD8+CD28− Tregs in the peripheral blood of the neonate with congenital CMV infection was higher than that in the controls at the three time points. The expression levels of perforin and granzyme B secreted by γδ T cells (Vδ1 and Vδ2 T cells), increased during the course of hospitalization until follow-up and were higher than those in the controls at the three time points. Conclusions: Despite the alleviation of clinical symptoms, developmental delay in later life remains inevitable in this intrauterine cCMV neonate. CD8+CD28− Tregs and Vδ1 and Vδ2 T cells secreting perforin and granzyme B may be involved in congenital CMV infection, although this hypothesis requires validation in a larger study. This report may contribute to our understanding of the effect of current treatment and the immune status of intrauterine cCMV-infected neonates. [ABSTRACT FROM AUTHOR]

Objective: To explore the application effect of mini clinical evaluation exercise (Mini-CEX) combined with direct observation of procedural skills (DOPS) in the standardized training of general practitioners in community clinics. Methods: From June 2022 to June 2023,20 general practitioners who received standardized training for residents in the general outpatient department of Changqing Community Health Service Center of Wuhan Fourth Hospital were collected as the research objects. Mini-CEX combined with DOPS was used to evaluate the general practitioners at the time of admission, 2 weeks of training and 4 weeks of training, and the results were fed back. Results: The scores of 20 general practitioners at 2 weeks and 4 weeks of training were compared with the scores at the time of admission, and the difference was statistically significant, p < 0.05. Conclusion: Mini-CEX combined with DOPS can improve the teaching effect of standardized training of residents in community general clinics. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is one of the most common autoimmune disorders characterized by the infiltration of immune cells into the brain and demyelination. The unwanted immunosuppressive side effect of therapeutically successful natalizumab led us to focus on the choroid plexus (CP), a key site for the first wave of immune cell infiltration in experimental autoimmune encephalomyelitis (EAE), for the control of immune cells trafficking. Adenosine A2A receptor (A2AR) is emerging as a potential pharmacological target to control EAE pathogenesis. However, the cellular basis for the A2AR-mediated protection remains undetermined.Methods: In the EAE model, we assessed A2AR expression and leukocyte trafficking determinants in the CP by immunohistochemistry and qPCR analyses. We determined the effect of the A2AR antagonist KW6002 treatment at days 8-12 or 8-14 post-immunization on T cell infiltration across the CP and EAE pathology. We determined the critical role of the CP-A2AR on T cell infiltration and EAE pathology by focal knock-down of CP-A2AR via intracerebroventricular injection of CRE-TAT recombinase into the A2ARflox/flox mice. In the cultured CP epithelium, we also evaluated the effect of overexpression of A2ARs or the A2AR agonist CGS21680 treatment on the CP permeability and lymphocytes migration.Results: We found the specific upregulation of A2AR in the CP associated with enhanced CP gateway activity peaked at day 12 post-immunization in EAE mice. Furthermore, the KW6002 treatment at days 8-12 or 8-14 post-immunization reduced T cell trafficking across the CP and attenuated EAE pathology. Importantly, focal CP-A2AR knock-down attenuated the pathogenic infiltration of Th17+ cells across the CP via inhibiting the CCR6-CCL20 axis through NFκB/STAT3 pathway and protected against EAE pathology. Lastly, activation of A2AR in the cultured epithelium by A2AR overexpression or CGS21680 treatment increased the permeability of the CP epithelium and facilitated lymphocytes migration.Conclusion: These findings define the CP niche as one of the primary sites of A2AR action, whereby A2AR antagonists confer protection against EAE pathology. Thus, pharmacological targeting of the CP-A2AR represents a novel therapeutic strategy for MS by controlling immune cell trafficking across CP. [ABSTRACT FROM AUTHOR]

Background: To explore the feasibility and safety of retroperitoneal laparoscopic partial nephrectomy with sequential segmental renal artery clamping for the patients with multiple renal tumor of who have solitary kidney or contralateral kidney insufficiency.Methods: Nine patients who have undergone retroperitoneal laparoscopic partial nephrectomy with sequential segmental renal artery clamping between October 2010 and January 2017 were retrospectively analyzed. Clinical materials and parameters during and after the operation were summarized.Results: Nineteen tumors were resected in nine patients and the operations were all successful. The operation time ranged from 100 to 180 min (125 min); clamping time of segmental renal artery was 10 ~ 30 min (23 min); the amount of blood loss during the operation was 120 ~ 330 ml (190 ml); hospital stay after the operation is 3 ~ 6d (5d). There was no complication during the perioperative period, and the pathology diagnosis after the surgery showed that there were 13 renal clear cell carcinomas, two papillary carcinoma and four perivascular epithelioid cell tumors with negative margins from the 19 tumors. All patients were followed up for 3 ~ 60 months, and no local recurrence or metastasis was detected. At 3-month post-operation follow-up, the mean serum creatinine was 148.6 ± 28.1 μmol/L (p = 0.107), an increase of 3.0 μmol/L from preoperative baseline.Conclusions: For the patients with multiple renal tumors and solitary kidney or contralateral kidney insufficiency, retroperitoneal laparoscopic partial nephrectomy with sequential segmental renal artery clamping was feasible and safe, which minimized the warm ischemia injury to the kidney and preserved the renal function effectively. [ABSTRACT FROM AUTHOR]

Background: The development of a dose-volume-histogram (DVH) estimation model for knowledge-based planning is very time-consuming and it could be inefficient if it was only used for similar upcoming cases as supposed. It is clinically desirable to explore and validate other potential applications for a configured model. This study tests the hypothesis that a supine volumetric modulated arc therapy (VMAT) model can optimize intensity modulated radiotherapy (IMRT) plans of other patient setup orientations.Methods: Based on RapidPlan, a DVH estimation model was trained using 81 supine VMAT rectal plans and validated on 10 similar cases to ensure the robustness of its designed purpose. Attempts were then made to apply the model to re-optimize the dynamic MLC-sequences of the duplicated IMRT plans from 30 historical patients (20 prone and 10 supine) that were treated with the same prescription as for the model (50.6 and 41.8 Gy to 95 % of PGTV and PTV simultaneously/22 fractions). The performance of knowledge-based re-optimization and the impact of setup orientations were evaluated dosimetrically.Results: The VMAT model validation on similar cases showed comparable target dose distribution and significantly improved organ sparing (by 10.77 ~ 18.65 %) than the original plans. IMRT plans of either setup can be re-optimized using the supine VMAT model, which significantly reduced the dose to the bladder (by 25.88 % from 33.85 ± 2.96 to 25.09 ± 1.32 Gy for D50 %; by 22.77 % from 33.99 ± 2.77 to 26.25 ± 1.22 Gy for mean dose) and femoral head (by 12.27 % from 15.65 ± 3.33 to 13.73 ± 1.43 Gy for D50 %; by 10.09 % from 16.26 ± 2.74 to 14.62 ± 1.10 Gy for mean dose), all P < 0.01. Although the dose homogeneity and PGTV conformity index (CI_PGTV) changed slightly (≤0.01), CI_PTV of IMRT plans was significantly increased (Δ = 0.17, P < 0.01) by the manually defined target-objectives in the VMAT optimizer. The semi-automated IMRT planning increased the global maximum dose and V107 % due to the missing of hot spot suppression by specific manual optimizing or fluence map editing.Conclusions: The Varian RapidPlan model trained on a technique and orientation can be used for another. Knowledge-based planning improves organ sparing and quality consistency, yet the target-objectives defined for VMAT-optimizer should be readapted to IMRT planning, followed by manual hot spot processing. [ABSTRACT FROM AUTHOR]

Background: Gap junctional intercellular communication (GJIC) is typically decreased in malignant tumors. Gap junction is not presented between hematopoietic cells but occurred in bone marrow stromal cells (BMSCs). Connexin 43 (Cx43) is the major gap junction (GJ) protein; our previous study revealed that Cx43 expression and GJIC were decreased in acute leukemic BMSCs. All-trans retinoic acid (ATRA) increases GJIC in a variety of cancer cells and has been used to treat acute promyelocytic leukemia, but the effects of ATRA on leukemic BMSCs is unknown. In this study, we evaluated the potential effects of ATRA on cell cycle, proliferation, and apoptosis of leukemic BMSCs. Effects of ATRA on Cx43 expression and GJIC were also examined. Methods: Human BMSCs obtained from 25 patients with primary acute leukemia, and 10 normal healthy donors were cultured. Effects of ATRA on cell cycle, cell proliferation, and apoptosis were examined with or without co-treatment with amphotericin-B. Cx43 expression was examined at both the mRNA and protein expression levels. GJIC was examined by using a dye transfer assay and measuring the rate of fluorescence recovery after photobleaching (FRAP). Results: ATRA arrested the cell cycle progression, inhibited cell growth, and increased apoptosis in leukemic BMSCs. Both Cx43 expression and GJIC function were increased by ATRA treatment. Most of the observed effects mediated by ATRA were abolished by amphotericin-B pretreatment. Conclusions: ATRA arrests cell cycle progression in leukemic BMSCs, likely due to upregulating Cx43 expression and enhancing GJIC function. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) are small non-coding RNAs that recognize sites of complementarity of target messenger RNAs, resulting in transcriptional regulation and translational repression of target genes. In Huntington's disease (HD), a neurodegenerative disease caused by a trinucleotide repeat expansion, miRNA dyregulation has been reported, which may impact gene expression and modify the progression and severity of HD. Methods: We performed next-generation miRNA sequence analysis in prefrontal cortex (Brodmann Area 9) from 26 HD, 2 HD gene positive, and 36 control brains. Neuropathological information was available for all HD brains, including age at disease onset, CAG-repeat size, Vonsattel grade, and Hadzi-Vonsattel striatal and cortical scores, a continuous measure of the extent of neurodegeneration. Linear models were performed to examine the relationship of miRNA expression to these clinical features, and messenger RNA targets of associated miRNAs were tested for gene ontology term enrichment. Results: We identified 75 miRNAs differentially expressed in HD brain (FDR q-value <0.05). Among the HD brains, nine miRNAs were significantly associated with Vonsattel grade of neuropathological involvement and three of these, miR-10b-5p, miR-10b-3p, and miR-302a-3p, significantly related to the Hadzi-Vonsattel striatal score (a continuous measure of striatal involvement) after adjustment for CAG length. Five miRNAs (miR-10b-5p, miR-196a-5p, miR-196b-5p, miR-10b-3p, and miR-106a-5p) were identified as having a significant relationship to CAG length-adjusted age of onset including miR-10b-5p, the mostly strongly over-expressed miRNA in HD cases. Although prefrontal cortex was the source of tissue profiled in these studies, the relationship of miR-10b-5p expression to striatal involvement in the disease was independent of cortical involvement. Correlation of miRNAs to the clinical features clustered by direction of effect and the gene targets of the observed miRNAs showed association to processes relating to nervous system development and transcriptional regulation. Conclusions: These results demonstrate that miRNA expression in cortical BA9 provides insight into striatal involvement and support a role for these miRNAs, particularly miR-10b-5p, in HD pathogenicity. The miRNAs identified in our studies of postmortem brain tissue may be detectable in peripheral fluids and thus warrant consideration as accessible biomarkers for disease stage, rate of progression, and other important clinical characteristics of HD. [ABSTRACT FROM AUTHOR]

Background: Habitual snoring, a prominent symptom of sleep-disordered breathing, is an important indicator for a number of health problems in children. Compared to adults, large epidemiological studies on childhood habitual snoring and associated predisposing factors are extremely scarce. The present study aimed to assess the prevalence and associated factors of habitual snoring among Chinese school-aged children.Methods: A random sample of 20,152 children aged 5.08 to 11.99 years old participated in a cross-sectional survey, which was conducted in eight cities of China. Parent-administrated questionnaires were used to collect information on children's snoring frequency and the possible correlates.Results: The prevalence of habitual snoring was 12.0% (14.5% for boys vs. 9.5% for girls) in our sampled children. Following factors were associated with an increased risk for habitual snoring: lower family income (adjusted odds ratio [OR] = 1.46), lower father's education (OR = 1.38 and 1.14 for middle school or under and high school of educational level, respectively), breastfeeding duration < 6 months (OR = 1.17), pregnancy maternal smoking (OR = 1.51), obesity (OR = 1.50), overweight (OR = 1.35), several respiratory problems associated with atopy and infection, such as chronic/allergic rhinitis (OR = 1.94), asthma (OR = 1.43), adenotonsillar hypertrophy (OR = 2.17), and chronic otitis media (OR = 1.31), and family history of habitual snoring (OR = 1.70).Conclusion: The prevalence of habitual snoring in Chinese children was similar to that observed in other countries. The potential predisposing factors covered socioeconomic characteristics, environmental exposures, chronic health problems, and family susceptibility. Compared to socioeconomic status and family susceptibility, environmental exposures and chronic health problems had greater impact, indicating childhood habitual snoring could be partly prevented by health promotion and environmental intervention. [ABSTRACT FROM AUTHOR]

Precision Medicine may be considered as another strategic effort of "from-bench-to-beside" translation. In order to have a maximal impact on population health, the translation must go further. A new translational medicine paradigm is proposed to improve the clarity of conceptual pathways and facilitate translation from research to health policy. The latter is particularly important in low- and middle-income countries where the need to improve population health is immediate and immense. [ABSTRACT FROM AUTHOR]

Background: Previous studies have postulated that sleep-disordered breathing (SDB) may be associated with the occurrence and exacerbation of asthma. However, there was limited quantitative evidence on the topic. This study aimed at investigating the prevalence and predisposing factors of asthma, and quantifying the association between SDB and asthma among school-aged children in China. In addition, a comprehensive meta-analysis of the published evidences and our findings were further conducted.Methods: To test the hypothesis, we conducted a multicentric cross-sectional study involving 22,478 children aged 5-12 years recruited from eight cities in China. Furthermore, a meta-analysis based on both previously published studies and our cross-sectional study was performed.Results: The prevalence rate of SDB and asthma was 12.0% and 3.5% among our cross-sectional study sample. It was demonstrated that symptoms of SDB, such as habitual snoring (OR = 1.28, 95%CI: 1.01-1.62), and obstructive sleep apnea (OSA) (OR = 1.92, 95%CI: 1.34-2.76), were significantly associated with asthma, after adjusting for potential confounding factors. In the meta-analysis, SDB was correlated with the prevalence of asthma in both children (OR = 1.58, 95%CI: 1.35-1.80) and adults (OR = 1.55, 95%CI: 1.42-1.67).Conclusions: Our results provide further evidence for the independent association between SDB and asthma. The clinical significance of our findings lies in the emphasis that children undergoing examination or treatment for asthma should be routinely screened for sleep problems. Further systematic study is required to illuminate the underlying mechanism. [ABSTRACT FROM AUTHOR]

Background: Intracranial aneurysms are pathological dilatations of the cerebral artery, while rupture of intracranial aneurysms causes life-threatening subarachnoid hemorrhage. The molecular mechanisms of pathogenesis of intracranial aneurysms are poorly understood. MicroRNAs have fundamental roles in modulating vascular biology and disease. In the present study, we carried out a genome-wide characterization on expressions of microRNAs, and performed integrative analyses in conjunction with changes of the transcriptome in human intracranial aneurysms.Methods: Genome-wide microRNA screening was performed in 6 intracranial aneurysmal samples and 6 normal superficial temporal arteries. Each case and control pair was individually matched with gender, age (±5 years), and high blood pressure history. Microarray analysis was performed using Agilent Human miRNA arrays.Results: As compared to normal arteries, we identified 157 microRNAs that were differentially expressed in the aneurysmal tissue (P < 0.05 and fold change ≥ 2), including 72 upregulated and 85 downregulated. The changed microRNAs included endothelium-enriched microRNAs such as members of the let-7 family, miR-17, miR-23b, miR-126, hsa-miR-24-1 and miR-222, and vascular smooth muscle-enriched miRNAs such as miR-143 and miR-145. Moreover, miR-1, miR-10a, miR-125b, and miR-26a, which were implicated in modulating vascular smooth muscle cell functions such as proliferation, apoptosis and shift of phenotype, were also changed. In contrast, microRNAs involved in monocyte and macrophage functions, such as miR-155, miR-146a, miR-223, and miR-124a, were not significantly changed. Bioinformatic analysis revealed that the changed microRNAs were associated with several biological processes related to aneurysm formation, including inflammation, dysregulation of extracellular matrix, smooth muscle cell proliferation, programmed cell death, and response to oxidative stress. Interestingly, we found that a subset of the potential microRNA target genes belonged to the protein translation machinery, including various eukaryotic translation initiation factors and ribosomal proteins, and this finding was highly correlated with our previous transcriptome data showing that multiple genes of the ribosomal proteins and translation initiation and elongation factors were significantly downregulated in human intracranial aneurysms.Conclusions: Our results support that dysregulated microRNAs may have a pathogenic role in intracranial aneurysms. Disruption of the protein translation process may have a pathogenic role in the development of intracranial aneurysms. [ABSTRACT FROM AUTHOR]

Translational medicine entails not only "from-bench-to-bedside" but also preventive medicine. The present article proposes a conceptual framework of translational research from scientific research to health care policy and public health policy. We highlight the importance of translational medicine to bridge between research and policy and share our experience of translating medical research to public health policy in China as well as obstacles and challenges we are facing in the translation process. [ABSTRACT FROM AUTHOR]

Background: Retinopathy of prematurity (ROP) remains a major cause of childhood blindness and current laser photocoagulation and anti-VEGF antibody treatments are associated with reduced peripheral vision and possible delayed development of retinal vasculatures and neurons. In this study, we advanced the translational potential of adenosine A2A receptor (A2AR) antagonists as a novel therapeutic strategy for selectively controlling pathological retinal neovascularization in oxygen-induced retinopathy (OIR) model of ROP. Methods: Developing C57BL/6 mice were exposed to 75% oxygen from postnatal (P) day 7 to P12 and to room air from P12 to P17 and treated with KW6002 or vehicle at different postnatal developmental stages. Retinal vascularization was examined by whole-mount fluorescence and cross-sectional hematoxylin-eosin staining. Cellular proliferation, astrocyte and microglial activation, and tip cell function were investigated by isolectin staining and immunohistochemistry. Apoptosis was analyzed by TUNEL assay. The effects of oxygen exposure and KW6002 treatment were analyzed by two-way ANOVA or Kruskal-Wallis test or independent Student's t-test or Mann-Whitney U test. Results: The A2AR antagonist KW6002 (P7-P17) did not affect normal postnatal development of retinal vasculature, but selectively reduced avascular areas and neovascularization, with the reduced cellular apoptosis and proliferation, and enhanced astrocyte and tip cell functions in OIR. Importantly, contrary to our prediction that A2AR antagonists were most effective at the hypoxic phase with aberrantly increased adenosine-A2AR signaling, we discovered that the A2AR antagonist KW6002 mainly acted at the hyperoxic phase to confer protection against OIR as KW6002 treatment at P7-P12 (but not P12-P17) conferred protection against OIR; this protection was observed as early as P9 with reduced avascular areas and reduced cellular apoptosis and reversal of eNOS mRNA down-regulation in retina of OIR. Conclusions: As ROP being a biphasic disease, our identification of the hyperoxic phase as the effective window, together with selective and robust protection against pathological (but not physiological) angiogenesis , elevates A2AR antagonists as a novel therapeutic strategy for ROP treatment. [ABSTRACT FROM AUTHOR]

Background: To explore the feasibility and safety of retroperitoneal laparoscopic partial nephrectomy with sequential segmental renal artery clamping for the patients with multiple renal tumor of who have solitary kidney or contralateral kidney insufficiency., Methods: Nine patients who have undergone retroperitoneal laparoscopic partial nephrectomy with sequential segmental renal artery clamping between October 2010 and January 2017 were retrospectively analyzed. Clinical materials and parameters during and after the operation were summarized., Results: Nineteen tumors were resected in nine patients and the operations were all successful. The operation time ranged from 100 to 180 min (125 min); clamping time of segmental renal artery was 10 ~ 30 min (23 min); the amount of blood loss during the operation was 120 ~ 330 ml (190 ml); hospital stay after the operation is 3 ~ 6d (5d). There was no complication during the perioperative period, and the pathology diagnosis after the surgery showed that there were 13 renal clear cell carcinomas, two papillary carcinoma and four perivascular epithelioid cell tumors with negative margins from the 19 tumors. All patients were followed up for 3 ~ 60 months, and no local recurrence or metastasis was detected. At 3-month post-operation follow-up, the mean serum creatinine was 148.6 ± 28.1 μmol/L (p = 0.107), an increase of 3.0 μmol/L from preoperative baseline., Conclusions: For the patients with multiple renal tumors and solitary kidney or contralateral kidney insufficiency, retroperitoneal laparoscopic partial nephrectomy with sequential segmental renal artery clamping was feasible and safe, which minimized the warm ischemia injury to the kidney and preserved the renal function effectively.

Precision Medicine may be considered as another strategic effort of "from-bench-to-beside" translation. In order to have a maximal impact on population health, the translation must go further. A new translational medicine paradigm is proposed to improve the clarity of conceptual pathways and facilitate translation from research to health policy. The latter is particularly important in low- and middle-income countries where the need to improve population health is immediate and immense.

Background: The development of a dose-volume-histogram (DVH) estimation model for knowledge-based planning is very time-consuming and it could be inefficient if it was only used for similar upcoming cases as supposed. It is clinically desirable to explore and validate other potential applications for a configured model. This study tests the hypothesis that a supine volumetric modulated arc therapy (VMAT) model can optimize intensity modulated radiotherapy (IMRT) plans of other patient setup orientations., Methods: Based on RapidPlan, a DVH estimation model was trained using 81 supine VMAT rectal plans and validated on 10 similar cases to ensure the robustness of its designed purpose. Attempts were then made to apply the model to re-optimize the dynamic MLC-sequences of the duplicated IMRT plans from 30 historical patients (20 prone and 10 supine) that were treated with the same prescription as for the model (50.6 and 41.8 Gy to 95 % of PGTV and PTV simultaneously/22 fractions). The performance of knowledge-based re-optimization and the impact of setup orientations were evaluated dosimetrically., Results: The VMAT model validation on similar cases showed comparable target dose distribution and significantly improved organ sparing (by 10.77 ~ 18.65 %) than the original plans. IMRT plans of either setup can be re-optimized using the supine VMAT model, which significantly reduced the dose to the bladder (by 25.88 % from 33.85 ± 2.96 to 25.09 ± 1.32 Gy for D50 %; by 22.77 % from 33.99 ± 2.77 to 26.25 ± 1.22 Gy for mean dose) and femoral head (by 12.27 % from 15.65 ± 3.33 to 13.73 ± 1.43 Gy for D50 %; by 10.09 % from 16.26 ± 2.74 to 14.62 ± 1.10 Gy for mean dose), all P < 0.01. Although the dose homogeneity and PGTV conformity index (CI&#95;PGTV) changed slightly (≤0.01), CI&#95;PTV of IMRT plans was significantly increased (Δ = 0.17, P < 0.01) by the manually defined target-objectives in the VMAT optimizer. The semi-automated IMRT planning increased the global maximum dose and V107 % due to the missing of hot spot suppression by specific manual optimizing or fluence map editing., Conclusions: The Varian RapidPlan model trained on a technique and orientation can be used for another. Knowledge-based planning improves organ sparing and quality consistency, yet the target-objectives defined for VMAT-optimizer should be readapted to IMRT planning, followed by manual hot spot processing.

Background: Gap junctional intercellular communication (GJIC) is typically decreased in malignant tumors. Gap junction is not presented between hematopoietic cells but occurred in bone marrow stromal cells (BMSCs). Connexin 43 (Cx43) is the major gap junction (GJ) protein; our previous study revealed that Cx43 expression and GJIC were decreased in acute leukemic BMSCs. All-trans retinoic acid (ATRA) increases GJIC in a variety of cancer cells and has been used to treat acute promyelocytic leukemia, but the effects of ATRA on leukemic BMSCs is unknown. In this study, we evaluated the potential effects of ATRA on cell cycle, proliferation, and apoptosis of leukemic BMSCs. Effects of ATRA on Cx43 expression and GJIC were also examined., Methods: Human BMSCs obtained from 25 patients with primary acute leukemia, and 10 normal healthy donors were cultured. Effects of ATRA on cell cycle, cell proliferation, and apoptosis were examined with or without co-treatment with amphotericin-B. Cx43 expression was examined at both the mRNA and protein expression levels. GJIC was examined by using a dye transfer assay and measuring the rate of fluorescence recovery after photobleaching (FRAP)., Results: ATRA arrested the cell cycle progression, inhibited cell growth, and increased apoptosis in leukemic BMSCs. Both Cx43 expression and GJIC function were increased by ATRA treatment. Most of the observed effects mediated by ATRA were abolished by amphotericin-B pretreatment., Conclusions: ATRA arrests cell cycle progression in leukemic BMSCs, likely due to upregulating Cx43 expression and enhancing GJIC function.

Background: Genetic heritability and expression study have shown that different diabetes traits have common genetic components and pathways. A computationally efficient pathway analysis of GWAS results will benefit post-GWAS study of SNP associations and identification of common genetic pathways from diabetes GWAS can help to improve understanding of the disease pathogenesis., Results: We proposed a uniform-score gene-set analysis (USGSA) with implemented package to unify different gene measures by a uniform score for identifying pathways from GWAS data, and use a pre-generated permutation distribution table to quickly obtain multiple-testing adjusted p-value. Simulation studies of uniform score for four gene measures (minP, 2ndP, simP and fishP) have shown that USGSA has strictly controlled family-wise error rate. The power depends on types of gene measure. USGSA with a two-stage study strategy was applied to identify common pathways associated with diabetes traits based on public dbGaP GWAS results. The study identified 7 gene sets that contain binding motifs at promoter region of component genes for 5 transcription factors (TFs) of FOXO4, TCF3, NFAT, VSX1 and POU2F1, and 1 microRNA of mir-218. These gene sets include 25 common genes that are among top 5% of the gene associations over genome for all GWAS. Previous evidences showed that nearly all of these genes are mainly expressed in the brain., Conclusions: USGSA is a computationally efficient approach for pathway analysis of GWAS data with promoted interpretability and comparability. The pathway analysis suggested that different diabetes traits share common pathways and component genes are potentially regulated by common TFs and microRNA. The result also indicated that the central nervous system has a critical role in diabetes pathogenesis. The findings will be important in formulating novel hypotheses for guiding follow-up studies.

Background: Unintentional injuries are a major cause of death among children. Data suggest that the retention of knowledge and skills about first aid declined over time. The purpose of this study was to assess the effects of pediatric first aid training among teachers., Methods: A stratified random sampling method was used to select 1,067 teachers. The selected trainees received pediatric first aid training. Follow-up assessments were conducted 6 months, 9 months and 4 years following the training. A standardized collection of demographics was performed, and participants were given a questionnaire to indicate knowledge of and emotions about first aid., Results: In the pretest, 1067 people responded with a mean of 21.0 correct answers to 37 questions, whereas in the post-test period, the mean score increased to 32.2 correct answers of 37 questions (P <0.001). There was a decrease in scores from post-test to 6 months, 9 months and 4 years after the training. However, the mean at the 6-month, 9-month and 4-year marks were higher than the pretest mean (P < 0.001). A total of 82.8% of the participants achieved a pass mark of 80% or above; 42.8% of participants achieved the pass mark at 6 months, 41.7% at 9 months and 11.7% at 4 years (compared with pre-test, P < 0.001). The mean score of the subjects' emotions in the post-test period increased to 81 (P < 0.001). The mean scores of emotions at 9 months or 4 years were higher than the pretest mean (P < 0.001). At the 4-year mark, the majority of preschool staff (>70%) had administered correct first aid for injuries., Conclusions: This study demonstrated that the acquisition of knowledge, both short and long term, significantly improves. Despite appreciable decreases in knowledge long term, knowledge retention was modest but stable.