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1.
J BUON ; 24(4): 1574-1580, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31646811

RESUMO

PURPOSE: The purpose of the present study was to detect the expression of miR-489 in pancreatic cancer (PC) tissues and cells, and to explore the effects of miR-489 on cell proliferation and apoptosis of human PC cells and to also uncover the underlying mechanism. METHODS: miR-489 expression was assessed by quantitative real time-polymerase chain reaction (qRT-PCR) in PC tissues and PANC-1 and HPDE6-C7 cell lines. The binding-site predictions by bioinformatics showed that AKT Serine/Threonine Kinase 3 (AKT3) might be a potential target of miR-489. AKT3 expression in PC tissues and cells was detected by qRT-PCR, luciferase report assay and Western blotting assay were used to verify the rationality of the target gene. The biological role of miR-489 on cell proliferation, cell cycle and apoptosis were determined in PANC-1 cells by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay and flow cytometry after transfection with miR-NC, miR-489 mimics and si-AKT3. RESULTS: Compared with normal adjacent tissues and normal pancreatic cells, the expression of miR-489 was markedly down-regulated in PC tissues and cells. AKT3 was considered as a downstream gene of miR-489 and it was found that the expression levels of miR-489 and AKT3 were inversely proportional to each other, which was further confirmed by luciferase and Western blot assays. In subsequent experiments, up-regulation of miR-489 by transfection with miR-489 mimics significantly inhibited cell proliferation, blocked the G1/S transition and induced cell apoptosis of PANC-1 cells. However, overexpression of AKT3 significantly counteracted the biological effects of miR-489. CONCLUSIONS: Our findings indicate that up-regulation of miR-489 could suppress PC cell proliferation and facilitate cell apoptosis through targeting AKT3. miR-489 and AKT3 might serve as potential targets in the therapy of PC.

2.
Int J Colorectal Dis ; 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31642970

RESUMO

INTRODUCTION: Epstein-Barr virus (EBV)-associated lymphoproliferative diseases (LPD) with digestive tract involvement in immunocompetent patients is rather rare. Since the symptoms of EBV-associated LPD involving the gastrointestinal tract in immunocompetent patients are similar to those of inflammatory bowel disease (IBD), most patients are initially misdiagnosed. CASE PRESENTATION: In this paper, we present two cases of EBV-associated T cell LPD involving the colon in immunocompetent patients and review the relevant literature. CONCLUSION: EBV serological testing may help in detecting this disease, and our findings suggest that histopathological evidence of EBV, such as the Epstein-Barr encoding region, is very important to establish the diagnosis.

3.
Medicine (Baltimore) ; 98(33): e16915, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415440

RESUMO

BACKGROUND: Chronic lymphocytic leukemia (CLL) is a rare hematological malignancy classified in the non-Hodgkin's lymphoma category. Ibrutinib, a first-in-class Bruton tyrosine kinase inhibitor has been approved for use in the treatment of CLL. This drug has shown beneficial effects including a higher overall response rate, sustained remissions, and a tolerable toxicity level. In this meta-analysis, we aimed to compare the adverse drug events which were associated with the use of ibrutinib for the treatment of patients with CLL. METHODS: A careful search was carried out through the Cochrane Central, EMBASE, MEDLINE (PubMed), and through www.ClinicalTrials.com. The following criteria for inclusion were considered: Both randomized trials and observational cohorts; Studies comparing the adverse drug events observed with the use of ibrutinib versus a control group for the treatment of CLL. The RevMan software (version 5.3) was used to carry out this analysis and the analyzed data were represented by risk ratios (RR) and 95% confidence intervals (CI). RESULTS: A total number of 2456 participants with CLL were included in this analysis. One thousand one hundred thirteen participants were treated with ibrutinib whereas the remaining 1343 participants were assigned to the control (non-ibrutinib) group. Results of this current analysis showed Ibrutinib not to be associated with significantly higher risk of anemia (RR: 0.90, 95% CI: 0.67-1.21; P = .49), thrombocytopenia (RR: 0.61, 95% CI: 0.32-1.14; P = .12), neutropenia (RR: 0.50, 95% CI: 0.25-1.00; P = .05), and febrile neutropenia (RR: 0.89, 95% CI: 0.32-2.49; P = .83) in these patients with CLL. The risk for respiratory tract infection was also similarly manifested (RR: 1.01, 95% CI: 0.78-1.30; P = .96). However, ibrutinib was associated with a high risk of abdominal manifestations in comparison to the control group (RR: 1.62, 95% CI: 1.32-2.00; P = .00001). The risk for diarrhea was also significantly higher in the Ibrutinib group (RR: 2.14, 95% CI: 1.44-3.17; P = .0002). CONCLUSIONS: During the treatment of CLL, ibrutinib was not associated with significantly higher risks of anemia, thrombocytopenia, or neutropenia compared to the control group. However, abdominal manifestations were significantly higher with ibrutinib. Advanced phase trials should further confirm this hypothesis.


Assuntos
Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Pirazóis/efeitos adversos , Pirimidinas/efeitos adversos , Dor Abdominal/induzido quimicamente , Constipação Intestinal/induzido quimicamente , Diarreia/induzido quimicamente , Feminino , Humanos , Masculino , Pirazóis/administração & dosagem , Pirimidinas/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Vômito/induzido quimicamente
4.
Diabetes Ther ; 2019 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-31256352

RESUMO

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a major health issue, especially in patients with coexisting coronary artery disease (CAD). Patients with insulin-treated T2DM (ITDM) have worse outcomes than those with non-insulin-treated T2DM. Very few studies have compared short-term to long-term adverse cardiovascular outcomes following percutaneous coronary intervention (PCI) in patients on insulin therapy. Therefore, in this meta-analysis, we systematically compared short-term to long-term adverse cardiovascular outcomes in a population of patients with ITDM following PCI. METHODS: We searched for English-language publications focusing on PCI in patients with ITDM using specific search terms/phrases. All the participants accepted for inclusion in this meta-analysis were treated with a drug-eluting stent. Post-intervention adverse cardiovascular outcomes observed during short-term and long-term follow-up periods were assessed and compared. Statistical analysis was carried out using the popular RevMan 5.3 software. Odd ratios (OR) with 95% confidence intervals (CI) were calculated. RESULTS: Six studies comprising 1568 participants with ITDM in total were included in this simple meta-analysis. Patient enrollment periods varied but enrollment occurred during the years 1993-2012. When a fixed-effects statistical model was used, post-PCI adverse cardiovascular outcomes-such as major adverse cardiac events (MACEs) (OR 3.33, 95% CI 2.64-4.21; P = 0.00001), all-cause mortality (OR 5.73, 95% CI 3.37-9.73; P = 0.00001), myocardial infarction (MI) (OR 1.47, 95% CI 1.05-2.07; P = 0.02), and repeated revascularization (OR 4.78, 95% CI 3.29-6.94; P = 0.00001)-were found to be significantly more likely during the long-term follow-up period. A similar result was observed with a random-effects statistical model. CONCLUSION: Adverse cardiovascular outcomes post PCI were significantly more likely during the long-term follow-up period than during the short-term follow-up period in these patients with T2DM on insulin therapy. This hypothesis requires confirmation via new comparative trials that consider short-term and long-term follow-up periods.

5.
Hum Mol Genet ; 2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-31127295

RESUMO

Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene-smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene-smoking interaction analysis and 38 were newly identified (P < 5 × 10-8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.

6.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(2): 134-139, 2019 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-30975277

RESUMO

Objective To explore the relationship between the drug resistance gene ATP binding cassette sub-family B member 4 (abcb4) in zebrafish and Wnt/ß-catenin signaling pathway. Methods Wild-type zebrafish and transgenic zebrafish were set in the blank control group, doxorubicin treatment group, vinblastine treatment group, gefitinib treatment group, doxorubicin combined with gefitinib treatment group, and vinblastine combined with gefitinib treatment group. The 100 embryos of each group were treated with drugs until the 5th day, and 50 zebrafish juveniles were tested on the 5th day in each group. The drug resistance of wild-type zebrafish was tested by rhodamine 123 experiment. The fluorescence intensity of transgenic zebrafish was tested by microplate reader, and the fluorescence distribution was tested by living cell workstation. The protein levels of transgenic zebrafish ß-catenin, GSK-3ß, ABCB4 and enhanced green fluorescent protein (EGFP) were tested by Western blot analysis. Results Rhodamine 123 experiments proved that there was drug resistance in zebrafish when treated with doxorubicin and vinblastine. Compared with the blank group, the EGFP fluorescence intensity increased in the transgenic zebrafish when treated with doxorubicin and vinblastine. Western blot assay showed the accumulation of ß-catenin accompanied by the increase of EGFP and ABCB4 proteins in the transgenic zebrafish exposed to adriamycin and vincristine. Conclusion The Wnt/ß-catenin signaling pathway in zebrafish is involved in the activation and drug resistance of zebrafish abcb4 gene.


Assuntos
Resistência a Medicamentos , Via de Sinalização Wnt , Proteínas de Peixe-Zebra , Peixe-Zebra , beta Catenina , Transportadores de Cassetes de Ligação de ATP/genética , Animais , Animais Geneticamente Modificados , Antineoplásicos/farmacologia , Resistência a Medicamentos/genética , Embrião não Mamífero/efeitos dos fármacos , Via de Sinalização Wnt/fisiologia , Proteínas de Peixe-Zebra/genética , beta Catenina/metabolismo
7.
Int Urogynecol J ; 30(6): 945-950, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30863945

RESUMO

INTRODUCTION AND HYPOTHESIS: This study aimed to assess the individual and interactive effects of delivery mode and age on the function of the external anal sphincter (EAS) by analyzing the motor unit properties with intramuscular electromyography (EMG). Results are expected to improve the understanding of delivery-related occult obstetric EAS injuries and its development over the aging process and further support early clinical detection and intervention. METHODS: A total of 49 postpartum women were recruited into four test groups according to their age and delivery mode: young vaginal delivery (Y-VD), elderly vaginal delivery (E-VD), young cesarean section (Y-CS), and elderly cesarean section (E-CS) groups. Anorectal ultrasonography, manometry, and intramuscular EMG were employed for comprehensive evaluation of EAS function. RESULTS: No significant difference in anorectal ultrasonography and most manometry measurements was associated with delivery age or mode. Intramuscular EMG, however, revealed a statistically significant difference in the characteristics of motor unit potentials (MUPs), including duration, turns, phases, and multiphase wave ratio between four subject groups. No significant interaction effect between age and delivery mode was found. CONCLUSIONS: Delivery mode and age have a significant effect on the neuromuscular function of the EAS, suggesting a potential protectiveness of cesarean section against impairment to the EAS. Our results do not provide significant evidence regarding the interaction effect of delivery mode and age; further investigations are needed to confirm this conclusion.

8.
J Am Med Dir Assoc ; 20(3): 312-316, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30824219

RESUMO

OBJECTIVE: To examine the association between body mass index (BMI) and outcomes, including discharge to home, hospitalization, death, or continued residence in the skilled nursing facilities (SNFs), among residents newly admitted to SNFs. DESIGN: Retrospective observational design using the national Minimum Data Set 2.0 from 2006 to 2010. SETTING: SNFs in the United States. PARTICIPANTS: Newly admitted SNF residents. MEASUREMENTS: Four discharge outcomes were assessed at 30 days subsequent to the initial admission to SNF, including discharge to home, hospitalization, death, or continued residence in the SNFs, and examined using a competing hazards model. SNF residents were categorized as underweight (BMI < 18.5), normal to overweight (18.5 ≤ BMI < 30), mildly obese (30 ≤ BMI < 35), and moderately to severely obese (BMI ≥ 35). RESULTS: The study sample was composed of 3,812,333 newly admitted SNF residents. As compared with normal to overweight SNF residents, underweight individuals were less likely [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.82-0.83] to be discharged home and more likely to be hospitalized (HR 1.06, 95% CI 1.05-1.07), or to die (HR 1.59, 95% CI 1.56-1.62), rather than continue to reside in the facility. Residents with mild obesity were more likely (HR 1.12, 95% CI 1.11-1.13) to be discharged home and less likely to be hospitalized (HR 0.96, 95% CI 0.95-0.97) or to die (HR 0.74, 95% CI 0.73-0.76). Moderately to severely obese individuals were also more likely to be discharged home (HR 1.11, 95% CI 1.10-1.11) and less likely to be hospitalized (HR 0.94, 95% CI 0.93-0.95) or die (HR 0.66, 95% CI 0.64-0.68). CONCLUSIONS/IMPLICATIONS: SNF residents with obesity experience more favorable short-term outcomes compared with underweight or normal to overweight residents. Underweight residents are at the greatest risk for adverse outcomes, emphasizing the need for special surveillance and preventive efforts targeting these individuals.

9.
Diabetes Ther ; 2019 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-30905057

RESUMO

INTRODUCTION: With recent advances in interventional cardiology where percutaneous coronary intervention (PCI) has become the most preferred invasive strategy and with advances in adjunctive pharmacotherapy, several newer oral P2Y12 inhibitors have reached the market. In this analysis, we aimed to compare the cardiovascular outcomes and bleeding events which were associated with the use of cangrelor versus clopidogrel in patients with type 2 diabetes mellitus (T2DM) 48 h after PCI. METHODS: The electronic databases MEDLINE (PubMed), www.ClinicalTrials.gov , EMBASE, and Cochrane central were searched for relevant publications comparing canagrelor with clopidogrel during PCI. Patients with T2DM were extracted. Adverse cardiovascular outcomes and bleeding events at 48 h follow-up were considered as the end points. This meta-analysis was carried out with the latest RevMan software (5.30). Odds ratios (OR) and 95% confidence intervals (CI) were used to represent the data. RESULTS: This analysis consisted of a total number of 5031 participants with T2DM (enrolled between the years 2006 and 2012). Compared to clopidgrel, use of cangrelor in these patients with T2DM was not associated with significantly different primary end point (OR 0.94, 95% CI 0.75-1.16; P = 0.55), myocardial infarction (OR 0.96, 95% CI 0.76-1.20; P = 0.71), all-cause death (OR 0.70, 95% CI 0.25-1.96; P = 0.49), ischemia-driven revascularization (OR 0.66, 95% CI 0.32-1.36; P = 0.26), and stent thrombosis (OR 0.45, 95% CI 0.17-1.17; P = 0.10). Thrombolysis in myocardial infarction (TIMI)-defined major and minor bleedings were similarly manifested: (OR 1.02, 95% CI 0.38-2.74; P = 0.96) and (OR 1.39, 95% CI 0.70-2.79; P = 0.35), respectively. Global use of strategies to open occluded arteries (GUSTO)-defined moderate and severe bleeding were also not significantly different: (OR 1.36, 95% CI 0.70-2.67; P = 0.37) and (OR 1.21, 95% CI 0.41-3.59; P = 0.74), respectively. However, GUSTO-defined mild bleeding and acute catheterization and urgent intervention triage strategy (ACUITY)-defined major and minor bleedings were significantly in favor of clopidogrel in comparison to cangrelor in these patients with T2DM: (OR 1.28, 95% CI 1.09-1.50; P = 0.003), (OR 1.43, 95% CI 1.05-1.94; P = 0.02), and (OR 1.23, 95% CI 1.04-1.46; P = 0.02), respectively. Other bleeding outcomes were not significantly different. CONCLUSIONS: In these patients with T2DM, cangrelor was comparable to clopidogrel in terms of efficacy at 48 h following PCI. However, it was associated with significantly higher mild GUSTO bleeding and major and minor ACUITY bleeding, therefore requiring further workups on its safety side. This hypothesis should be explored further and confirmed in other forthcoming trials based strictly on patients with T2DM.

10.
Sci Rep ; 9(1): 1800, 2019 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-30755687

RESUMO

Genome-Wide Association (GWA) with population-based imputation (PBI) has been successful in identifying common variants associated with complex diseases; however, much heritability remains to be explained and low frequency variants (LFV) may contribute. To identify LFV, a study of unrelated individuals may no longer be as efficient as a family study, where rare population variants can be frequent in families. Family-based imputation (FBI) provides an opportunity to evaluate LFV. To compare the performance of PBI and FBI, we conducted extensive simulations, generating genotypes using SeqSIMLA from various reference panels for families. We masked genotype information for variants unavailable in Framingham 550 K GWA genotype data in less informative subjects selected by GIGI-Pick. We implemented IMPUTE2 with duoHMM in SHAPEIT (Impute2_duoHMM) for PBI, MERLIN and GIGI for FBI and PedBLIMP for a hybrid approach. In general, FBI in both MERLIN and GIGI outperformed other approaches with imputation accuracy greater than 0.99 for the squared correlation and imputation quality scores (IQS) especially for LFV, although imputation accuracy from MERLIN depends on pedigree splitting for larger families. PBI performed worst with the exception of good imputation accuracy for common variants when a closely ancestry matched reference is used. In summary, linkage disequilibrium (LD) information from large available genotype resources provides good imputation for common variants with well-selected reference panels without requiring densely sequenced data in family members, while imputation of LFV with FBI benefits more from information on inheritance patterns within families yielding better imputation.

11.
Artigo em Inglês | MEDLINE | ID: mdl-30689774

RESUMO

Background: Obesity prevalence has been increasing over decades among the U.S. population. This study analyzed trends in obesity prevalence among long-stay nursing home residents from 2005 to 2015. Methods: Data came from the Minimum Data Sets (2005-2015). The study population was limited to long-stay residents (ie, those residing in a nursing home ≥100 days in a year). Residents were stratified into body mass index (BMI)-based groups: underweight (BMI < 18.5), normal weight (18.5 ≤ BMI < 25), overweight (25 ≤ BMI < 30), and obese (BMI ≥ 30); residents with obesity were further categorized as having Class I (30 ≤ BMI < 35), Class II (35 ≤ BMI < 40), or Class III (BMI ≥ 40) obesity. Minimum Data Sets assessments for 2015 were used to compare clinical and functional characteristics across these groups. Results: Obesity prevalence increased from 22.4% in 2005 to 28.0% in 2015. The prevalence of Class III obesity increased from 4.0% to 6.2%. The prevalence of underweight, normal weight, and overweight decreased from 8.5% to 7.2%, from 40.3% to 37.1%, and from 28.9% to 27.8%, respectively. In 2015, compared with residents with normal weight, residents with obesity were younger, were less likely to be cognitively impaired, had high levels of mobility impairment, and were more likely to have important medical morbidities. Conclusions and Relevance: There was a steady upward trend in obesity prevalence among nursing home residents for 2005-2015. Medical and functional characteristics of these residents may affect the type and level of care required, putting financial and staffing pressure on nursing homes.

12.
Medicine (Baltimore) ; 98(1): e14025, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30608455

RESUMO

BACKGROUND: Nowadays 57% of the cardiologists based in the United Kingdom and 32% of the cardiologists based in Canada utilize same day discharge (SDD) following elective percutaneous coronary intervention (PCI) as a routine practice. In this analysis, we aimed to systematically assess early versus late clinical outcomes following SDD after elective PCI. METHODS: The Medical Literature Analysis and Retrieval System Online, the Cochrane Central, the Resources from the United States National Library of Medicine (www.ClinicalTrials.gov: http://www.clinicaltrials.gov) and EMBASE were carefully searched for relevant English publications which reported early versus late clinical outcomes in patients who were discharged on the same day following revascularization by PCI. Relevant clinical outcomes which were reported in the original studies were considered as the endpoints in this analysis. Odd ratios (OR) and 95% confidence intervals (CI) were used to represent the data, and RevMan 5.3 was used as the statistical software. RESULTS: A total number of 21, 687 participants (enrollment time period from the year 1998 to the year 2015) were assigned to this analysis. When early versus late clinical outcomes were compared in patients who were discharged on the same day following elective PCI, major adverse cardiac events (OR: 0.75, 95% CI: 0.31-1.79; P = .51), mortality (OR: 0.26, 95% CI: 0.06-1.06; P = .06), stroke (OR: 1.46, 95% CI: 0.72-2.94; P = .29), arrhythmia (OR: 1.30, 95% CI: 0.64-2.63; P = .47), hematoma (OR: 1.00, 95% CI: 0.60-1.66; P = 1.00) and major bleeding from access site (OR: 1.68, 95% CI: 0.22-12.85; P = .62) were not significantly different. Post-procedural myocardial infarction (OR: 2.01, 95% CI: 0.71-5.70; P = .19) and minor bleeding from access site (OR: 6.61, 95% CI: 0.86-50.66; P = .07) were also similarly manifested. However, re-hospitalization was significantly higher in those patients with late clinical outcomes (OR: 0.18, 95% CI: 0.07-0.44; P = .0002). CONCLUSIONS: In those patients who were discharged from the hospital on the same day following elective PCI, no significant difference was observed in the assessed early versus late clinical outcomes. However, late clinical outcomes resulted in a significantly higher rate of re-hospitalization. Larger studies should confirm this hypothesis.


Assuntos
Procedimentos Cirúrgicos Eletivos/métodos , Hospitalização/estatística & dados numéricos , Alta do Paciente/normas , Intervenção Coronária Percutânea/efeitos adversos , Idoso , Canadá/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Reino Unido/epidemiologia , Estados Unidos/epidemiologia
13.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 47(1): 57-63, 2018 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-30146812

RESUMO

OBJECTIVE: : To observe the expression of g6pd gene in the early development stage of wild zebrafish embryos. METHODS: : The collinearity of g6pd gene and the sequence similarity of G6pd protein were analyzed with gene database and BLAST software, respectively. Expression of g6pd gene in different development stages of zebrafish embryos was detected by in situ hybridization. The g6pd-EGFP-pCS2+ recombinant plasmids were microinjected into zebrafish embryos, and fluorescence was observed under a fluorescence microscope. The expression of G6pd protein at 24, 48 and 72 hour post fertilization (hpf) zebrafish embryos was detected by Western blotting; the enzyme activity of G6pd at 24, 48 and 72 hpf zebrafish embryos was detected by modified G6pd quantitative ratio method. RESULTS: : The G6pd protein similarity of zebrafish and human was 88%, and that of zebrafish and mouse was 87%. The results of in situ hybridization showed that the g6pd gene was mainly expressed in the hematopoietic tissues of zebrafish; the results observed after microinjection of g6pd-EGFP-pCS2+ recombinant plasmid were consistent with the results of in situ hybridization. At 24, 48 and 72 hpf, the relative expression levels of G6pd protein in zebrafish embryos were 1.44±0.03, 1.47±0.05, and 1.54±0.02, respectively(P>0.05); the G6pd enzyme activity levels were 1.74±0.17, 1.75±0.12, 1.71±0.22, respectively (P>0.05). CONCLUSIONS: : The study has observed the expression of g6pd gene and G6pd protein, and G6pd enzyme activity in zebrafish embryos at different development phases, which provides a reference for the establishment of a zebrafish G6PD deficiency model.

14.
Gynecol Endocrinol ; : 1-3, 2018 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-30044146

RESUMO

To explore the genetic relationships between LRH-1 (rs2816948), CYP19 (rs727479 and rs700518), and P450scc (rs4077582) as a potential mechanism behind unexplained recurrent spontaneous abortions in a Chinese Han population. A case-control study was used and featured two groups: Patients with unexplained recurrent miscarriage (n = 82, abortion group) and those who voluntary surrendered of a normal early pregnancy (n = 97, control group). Abortion villi samples were obtained from all patients. Genomic DNA was later extracted and sequenced, after which statistical analyses performed to assess the relationship between single nucleotide polymorphisms and unexplained recurrent spontaneous abortions. There were significant differences in the genotypic and allelic distribution (p < .05) for CYP19 (rs727479) between the abortion and the control groups. There were no significant differences in the genotypic or allelic distributions (p > .05) for either the LRH-1 (rs2816948) or CYP19 (rs700518). There were also significant genotypic differences (p < .05) for P450scc (rs4077582), but no significant differences for its allelic distribution (p > .05). There was a significant correlation between the occurrence of unexplained recurrent spontaneous abortion and CYP19 (rs727479) single nucleotide polymorphisms.

15.
J Gerontol A Biol Sci Med Sci ; 73(10): 1403-1409, 2018 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-29506037

RESUMO

Background: To examine the association between body mass index (BMI) and the risk for falls and hip fractures among nursing home (NH) residents. Methods: A cohort study of newly admitted NH residents, excluding those with a prior history of hip fracture. Using the Minimum Data Set 2.0 (2006-2010), we determined the occurrence of new falls and hip fractures among NH residents during their first 3 months of stay. Residents were categorized as underweight (BMI < 18.5), normal-to-overweight (18.5 ≤ BMI < 30), mildly obese (30 ≤ BMI < 35), and moderately-to-severely obese (BMI ≥ 35). Results: Among newly admitted NH residents over the first 3 months, 51.1% of underweight residents, 53.1% of normal-to-overweight residents, 49.1% of residents with mild obesity, and 43.1% of residents with moderate-to-severe obesity experienced a fall; 3.1% of underweight residents, 2.5% of normal-to-overweight residents, 1.5% of residents with mild obesity, and 1.1% of residents with moderate-to-severe obesity experienced a hip fracture. In comparison with normal-to-overweight residents, after adjustment for resident-level and facility-level characteristics, mildly obese residents (odds ratio [OR] = 0.94, 95% confidence interval [CI] = [0.91-0.93]), and moderately-to-severely obese residents (OR = 0.84 [95% CI = 0.83-0.85]) were less likely to experience a fall; Mildly obese residents (OR = 0.65 [95% CI = 0.63-0.68]), and moderately-to-severely obese residents (OR = 0.84 [95% CI = 0.83-0.85]) were less likely, and underweight residents were more likely (OR = 1.22 [95% CI = 1.18-1.26]) to experience a hip fracture. Conclusion: Obesity is associated with reduced risks for falls and hip fractures among newly admitted NH residents. Future studies are needed to explore possible explanations for these associations.

16.
Int Heart J ; 59(2): 361-366, 2018 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-29479015

RESUMO

The abnormalities of blood pressure (BP) nocturnal decline have been found to be predictive for carotid plaque and lacunar infarction in patients with hypertension. In this study, BP dipping patterns in postmenopausal females with hypertension were investigated. The nocturnal decline of systolic BP (SBP) was evaluated using 24-hour ambulatory BP monitoring (ABPM). A total of 163 postmenopausal females were eventually included in our study. The prevalence of reverse-dipper BP pattern was 32.3% in females with menopause age in their 40s and 40% in their 50s. However, after multivariate logistic regression analysis, menopause age was shown to be an independent risk factor for BP reverse dipping (Odds ratio [OR] 1.148; 95%CI 1.020 - 1.292; P = 0.020). Moreover, menopause age was negatively correlated with the decline rate of nocturnal SBP (r = -0.159; P < 0.05) and diastolic BP (r = -0.161; P < 0.05). Our study suggested that the menopause age might serve as a risk factor for reverse-dipper BP pattern in postmenopausal females with hypertension.


Assuntos
Ritmo Circadiano/fisiologia , Hipertensão Essencial/fisiopatologia , Pós-Menopausa/fisiologia , Fatores Etários , Idoso , Monitorização Ambulatorial da Pressão Arterial , China , Feminino , Humanos , Pessoa de Meia-Idade
17.
Am J Hum Genet ; 102(3): 375-400, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29455858

RESUMO

Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined ∼18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p < 5 × 10-8) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p < 5 × 10-8). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling (MSRA, EBF2).

18.
Am J Hum Genet ; 102(1): 88-102, 2018 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-29304378

RESUMO

Bone mineral density (BMD) assessed by DXA is used to evaluate bone health. In children, total body (TB) measurements are commonly used; in older individuals, BMD at the lumbar spine (LS) and femoral neck (FN) is used to diagnose osteoporosis. To date, genetic variants in more than 60 loci have been identified as associated with BMD. To investigate the genetic determinants of TB-BMD variation along the life course and test for age-specific effects, we performed a meta-analysis of 30 genome-wide association studies (GWASs) of TB-BMD including 66,628 individuals overall and divided across five age strata, each spanning 15 years. We identified variants associated with TB-BMD at 80 loci, of which 36 have not been previously identified; overall, they explain approximately 10% of the TB-BMD variance when combining all age groups and influence the risk of fracture. Pathway and enrichment analysis of the association signals showed clustering within gene sets implicated in the regulation of cell growth and SMAD proteins, overexpressed in the musculoskeletal system, and enriched in enhancer and promoter regions. These findings reveal TB-BMD as a relevant trait for genetic studies of osteoporosis, enabling the identification of variants and pathways influencing different bone compartments. Only variants in ESR1 and close proximity to RANKL showed a clear effect dependency on age. This most likely indicates that the majority of genetic variants identified influence BMD early in life and that their effect can be captured throughout the life course.

19.
Nat Commun ; 9(1): 260, 2018 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-29343764

RESUMO

Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7×10-9 at rs8018720 in SEC23A, and P = 1.9×10-14 at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.

20.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 43(12): 1345-1350, 2018 Dec 28.
Artigo em Chinês | MEDLINE | ID: mdl-30643051

RESUMO

OBJECTIVE: To explore the risk factors for and the pathogenic mechanisms of pelvic organ prolapse and urinary incontinence.
 Methods: A total of 2 668 females who completed pelvic floor functional detection from July 2014 to October 2015 in the Physical Examination Center of the Third Xiangya Hospital of Central South University. The patients were divide into 4 groups: an urinary incontinence group, an organ prolapse group, an organ prolapse with urinary incontinence group, and a normal group. We compared the age, BMI, menopause, gravidity and parity, delivery pattern, the coordination of pelvic floor and abdominal muscles among the 4 groups.
 Results: There were statistical differences in age and BMI values among the 4 groups (P<0.05).There were statistical differences in menopause rate, gravidity and parity history among the normal group and the other 3 groups (P<0.05), and between the organ prolapse group and the organ prolapse with urinary incontinence group (P<0.05). However, the urinary incontinence group was not statistically different from the organ prolapse group and the normal group (P>0.05). In the mode of delivery, there were statistical difference among the normal group and the other 3 groups (P<0.05), and between the organ prolapse group with urinary incontinence group and the organ prolapse or the urinary incontinence group (P<0.05). There was no significant difference between the urinary incontinence group and the organ prolapse group (P>0.05). Among the 4 groups, the normal group was the best one in coordination between pelvic floor and abdominal muscles, following by the organ prolapse group, the pelvic organ prolapse group and the urinary incontinence group.
 Conclusion: Aging, menopause, number of pregnancies and delivery, BMI, and mode of delivery all affect the occurrence of pelvic organ prolapse and urinary incontinence. Females with urinary incontinence or organ prolapse are not good in coordination between the pelvic floor and abdominal muscles.


Assuntos
Prolapso de Órgão Pélvico , Incontinência Urinária , Feminino , Humanos , Diafragma da Pelve/patologia , Prolapso de Órgão Pélvico/patologia , Gravidez , Fatores de Risco , Incontinência Urinária/patologia
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