RESUMO
The clinical data of five cases of relapsed/refractory (R/R) Philadelphia chromosome-positive acute B-lymphocytic leukaemia (Ph+B-ALL) treated with Bcl-2 inhibitor venetoclax combined with tyrosine kinase inhibitor (TKI) and dexamethasone-containing low-dose chemotherapy regimen at Zhengzhou University Cancer Hospital were analyzed, and the efficacy and safety were evaluated. Ponatinib was used in two of the five patients with T315I mutation, and flumatinib was used in other three patients. The results showed that, of the four minimal residual disease (MRD) positive patients, three achieved complete molecular remission (CMR) in the short term and one was ineffective. Another patient with morphological recurrence reached CR in one month. The overall response rate was 80%. Treatment related adverse reactions included mild skin pigmentation, gastrointestinal reactions, fatigue, and grade â -â ¡ bone marrow suppression.
Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes , Leucemia-Linfoma Linfoblástico de Células Precursoras , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Dexametasona/uso terapêutico , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Inibidores de Proteínas Quinases/uso terapêutico , SulfonamidasRESUMO
Objective: To evaluate the predictive value of a multiparametric cardiac magnetic resonance (CMR) approach for ventricular remodeling in ST-segment-elevation myocardial infarction (STEMI) patients with mildly reduced or preserved left ventricular ejection fraction (LVEF). Methods: This study is a prospective cohort study. STEMI patients with acute LVEF>40% after primary percutaneous coronary intervention (PCI) in Beijing Anzhen Hospital from October 2019 to September 2021 were enrolled. All patients received acute (3-7 days) and follow-up (3 months) CMR post-PCI. According to absence or presence of ventricular remodeling, patients were divided into ventricular remodeling group and non-ventricular remodeling group. Basic clinical characteristics and CMR indicators were analyzed and compared between the two groups. Logistic regression and receiver operating characteristic (ROC) curves were used to explore the predictive performance of CMR high-risk attributes for ventricular remodeling in STEMI patients with mildly reduced or preserved LVEF. The predictive value of combining multiple high-risk characteristics of CMR for ventricular remodeling was analyzed and compared with the traditional clinical risk factor model. Results: A total of 123 STEMI patients were enrolled (aged (57.1±11.1) years, 102 (82.9%) males). There were 97 cases (78.9%) patients in the non-ventricular remodeling group and 26 cases (21.1%) in the ventricular remodeling group. After adjustment for clinical risk factors, stroke volume<51.6 ml, global circumferential strain>-13.7%, infarct size>39.2%, microvascular obstruction>0.5%, and myocardial salvage index<43.9 were independently associated with ventricular remodeling in STEMI patients with mildly reduced or preserved LVEF. The incidence of ventricular remodeling increased with the increasing number of CMR high-risk attributes (P<0.01). The number of CMR high-risk attributes ≥3 was an independent predictor of adverse remodeling (adjusted OR=5.95, 95 CI%: 2.25-15.72, P<0.01) in STEMI patients with mildly reduced or preserved LVEF. Furthermore, the number of CMR high-risk attributes had incremental predictive value over baseline clinical risk factors (area under curve: 0.843 vs. 0.696, P<0.01). Conclusions: In STEMI patients with mild reduced or preserved LVEF, 5 CMR characteristics are associated with ventricular remodeling. The combination of ≥3 CMR high-risk characteristics is an independent predictor of ventricular remodeling, which has incremental predictive value beyond traditional risk factors in this patient cohort.
Assuntos
Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Feminino , Humanos , Imagem Cinética por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Estudos Prospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Volume Sistólico , Função Ventricular Esquerda , Remodelação VentricularRESUMO
Objective: To investigate related factors for microalbuminuria in adult type 1 diabetes (T1D) patients of short disease duration (less than 5 years), and provide evidence for prevention of early diabetic kidney disease in this population. Methods: All adult patients enrolled in the Guangdong T1D translational medicine study between 2011 and 2017 with a disease duration of less than 5 years were included in this analysis. At enrollment, patients' demographic and clinical data were documented, and blood and urine samples were collected for the measurements of blood lipids, glycated hemoglobin A1c and urine albuminuria. Insulin resistance was evaluated by estimated glucose disposal rate (eGDR). Patients were categorized into groups based on urine albumin creatitine ratio (UACR): normoalbuminuric group (UACR<30 mg/g) and microalbuminuric group (UACR≥30 mg/g). Stepwise multivariate linear regression analysis was used to analyze risk factors for microalbuminuria in adult T1D patients of short disease duration. Results: A total of 384 patients were included in this analysis, and 51.3% (197/384) of which was female. The onset age of patients was (24.6±12.5) years, with a disease duration of 2.1(0.6, 3.5) years, body mass index of (19.8±3.2) kg/m(2), waist hip ratio of 0.85±0.21, and glycated hemoglobin A1c of (9.8±3.3)% at enrollment. Microalbuminuria occurred in 62 patients (16.1%). Multivariate linear analysis showed that higher glycated hemoglobin A1c, higher systolic blood pressure and more severe insulin resistance were related factors for microalbuminuria (t=2.322, 2.868 and -2.373, respectively, all P<0.05). Conclusions: Microalbuminuria was not rare in adult T1D patients of short disease duration. Inadequate glycemic control and insulin resistance were independent related factors for microalbuminuria in this population.
Assuntos
Diabetes Mellitus Tipo 1 , Nefropatias Diabéticas , Adulto , Albuminúria , Glicemia , Pressão Sanguínea , Feminino , Hemoglobinas Glicadas , HumanosRESUMO
Objective: To explore the risk factors and prognoses of new-onset atrial fibrillation (NOAF) in patients with acute myocardial infarction (AMI). Methods: A total of 468 patients with AMI were admitted into Beijing Anzhen Hospital for emergency pereutaneous coronary intervention (PCI). According to the NOAF occurred during hospitalization, the patients were divided into two groups: the NOAF (n=37) group and the non-NOAF (n=431) group. Parameters including general clinical conditions, coronary lesions, echocardiography, biochemical markers, C-reactive protein (CRP) , N-terminal pro-brain natriuretic peptide (NT-pro-BNP), and myocardial markers were collected. In-hospital mortality and incidence of in-hospital main adverse cardiovascular and cerebrovascular events (MACCE) were compared between the two groups. Logistic multivariate regression analyses were performed for the association between the risk factors and NOAF. Results: The incidence of NOAF was 7.9% in AMI patients undergoing emergency PCI. There were no significant differences in door-to-balloon time, weight, platelet counts, baseline serum creatinine (SCr), postoperative SCr, triglyceride, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, uric acid, glycosylated hemoglobin A1c, preoperative medication, number of lesions, thrombus aspiration, location of myocardial infarction, and history of hypertension, diabetes, peripheral vascular disease and old myocardial infarction between the two groups. The percentage of women was in the NOAF group (32.4% vs. 16.7%, P<0.05) and subjects in this group were significantly elder than those in the non-NOAF groups [(66±10) years vs. (571±11) years, P<0.001]. Moreover, the levels of no-reflow rate (40.5% vs. 12.6%, P<0.001) , CRP [25.2 (15.43, 29.97) mg/L vs.5.21 (2.33, 16.98) mg/L, P<0.001], white blood cell counts [(11.19±3.44)×10(9) vs. (9.91±3.23)×10(9), P=0.022], NT-pro-BNP [(652.6±108.8) ng/L vs. (258.3±105.9) ng/L, P<0.001], and troponin I (TnI) [20.41(1.78, 87.89) µg/L vs.7.72(1.29, 36.39) µg/L, P=0.006] were significantly higher in the NOAF group than in the non-NOAF group, while left ventricular ejection fraction [(47.70±7.34)% vs. (53.35±8.05)%, P<0.001], and hemoglobin [137.0(125.5, 146.0) g/L vs.144.0(133.0,156.0) g/L, P=0.042] were significantly lower in the NOAF group than the non-NOAF group. Patients in the NOAF group had significantly longer hospital stay than those in the non-NOAF group [(8.7±5.6) d vs. (6.0±2.3) d, P=0.007]. The in-hospital mortality (8.1% vs 1.4% P=0.004) and the incidence of in-hospital MACCE (37.8% vs. 7.7%, P<0.001) in the NOAF group were significantly higher than those in the non-NOAF group. Logistic multivariate regression analyses showed that age (HR 1.083, 95%CI 1.028-1.141, P=0.003), CRP (HR 1.116, 95%CI 1.049-1.187, P=0.001), NT-pro-BNP (HR 1.463, 95%CI 1.001-4.064, P=0.001) and no-reflow (HR 4.388, 95%CI 1.006-19.144, P=0.049) were independent predictors of NOAF after AMI. Conclusions: Age, elevated levels of CRP, NT-pro-BNP, and the absence of no-reflow are risk factors for incident NOAF in patients with AMI in hospital.
Assuntos
Fibrilação Atrial/epidemiologia , Fibrilação Atrial/terapia , Infarto do Miocárdio/cirurgia , Idoso , Fibrilação Atrial/sangue , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Intervenção Coronária Percutânea , Prognóstico , Fatores de RiscoRESUMO
To retrospectively analyze the safety and efficacy of low dose subcutaneous decitabine combined with arsenic trioxide in patients with intermediate or high-risk myelodysplastic syndrome (MDS). Three of the total 11 MDS patients achieved complete remission (CR) and 6 achieved hematological improvement (HI), 1 stable disease (SD), and 1 progressive disease (PD). One patient was treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). The median follow-up time was 413(90-1 275) d. Nine patients were still alive. Low dose subcutaneous decitabine combined with arsenic trioxide can be an alternative regimen for intermediate or high-risk MDS patients.
Assuntos
Trióxido de Arsênio/uso terapêutico , Decitabina/administração & dosagem , Síndromes Mielodisplásicas/tratamento farmacológico , Trióxido de Arsênio/administração & dosagem , Decitabina/uso terapêutico , Humanos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The efficacy and safety of co-transplantation of unrelated donor peripheral blood stem cells (UD-PBSCs) combined with umbilical cord mesenchymal stem cells (UC-MSCs) in refractory severe aplastic anemia-â ¡(RSAA-â ¡) were analyzed retrospectively. Fifteen patients with RSAA-â ¡ underwent UD-PBSCs and UC-MSCs co-transplantation, among whom 14 cases had hematopoietic reconstitution without severe graft versus-host disease (GVHD). The 5-year overall survival rate was 78.57%. Combination of UD-PBSCs and UC-MSCs transplantation could be a safe and effective option for RSAA-â ¡.
Assuntos
Anemia Aplástica/cirurgia , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/fisiologia , Cordão Umbilical/fisiologia , Doadores não Relacionados , Anemia Aplástica/imunologia , Anemia Aplástica/mortalidade , Anemia Aplástica/patologia , China/epidemiologia , Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Células-Tronco Hematopoéticas/imunologia , Humanos , Células-Tronco Mesenquimais , Células-Tronco de Sangue Periférico , Estudos Retrospectivos , Taxa de Sobrevida , Doadores de Tecidos , Condicionamento Pré-Transplante/métodos , Resultado do Tratamento , Cordão Umbilical/imunologiaRESUMO
Objective: To observe the changes of intestinal barrier function in patients with acute severe organophosphorus pesticide poisoning (ASOPP) and the effect of early enteral nutrition on them. Methods: A single-center, single-sample, prospective, randomized controlled clinical trial was conducted. A total of 50 patients with ASOPP were divided into 24 h enteral nutrition group (group A) and 48 h (48-72 h) enteral nutrition group (B group) according to the order of hospitalization. The two groups received equal calorie nutritional support, and Serum D-lactic acid (D-LA) and serum human diamine oxidase (DAO) were detected immediately after admission and at 48 h, 72 h and 144 h. At the same time, the worst value of APACHE-â ¡ score was recorded, and the correlation between DAO, D-LA and APACHE-â ¡ score was analyzed. The serum concentration of D-LA and DAO in 15 healthy adults were detected as healthy control group. Results: There was no statistical difference in gender, age, poisoning time and organophosphorus pesticide components between group A and B (P>0.05). The distribution of D-LA concentration in group A poisoned patients at admission, 48 h, 72 h and 144 h was (66±19) µg/L, (68±21) µg/L, (66±19) µg/L, (63±17) µg/L, while in group B they were (62±15) µg/L, (58±17) µg/L, (58±16) µg/L, (67±9) µg/L. There was no statistical difference between the two groups in D-LA concentration and that of healthy people [(67±17) µg/L, P>0.05]. The distribution of DAO concentration in group A poisoned patients at admission, 48 h, 72 h and 144 h was (2.1±0.6) µg/ml, (2.1±0.5) µg/ml, (2.2±0.4) µg/ml, (2.2±0.5) µg/ml, while in group B they were (2.1±0.5) µg/ml, (2.1±0.5) µg/ml, (2.2±0.5) µg/ml, (2.1±0.4) µg/ml. DAO concentration in the early stage of the intoxication of the two groups were higher than that of healthy people (0.1±0.0 µg/ml) (P<0.05). There is no statistical difference in DAO concentration between group A and B at different time points (P>0.05). The APACHEE-â ¡ score of 48 hours and 72 hours in group A (12.2+1.7, 5.5+2.1) was significantly lower than that in group B (14.1+2.4, 8.2+2.6) (P<0.05). D-LA, DAO concentration at different time points was not correlated with APACHE-â ¡ score (P>0.05). D-LA (r, P) was immediate admission (-0.17, 0.24), 48 h (0.04, 0.79), 72 h (0.32, 0.06), 144 h (0.29, 0.07), and DAO (r, P) was immediate admission (-0.12, 0.43), 48 h (0.02, 0.92), 72 h (0.03, 0.85), 144 h (0.03, 0.82). Conclusions: Patients with ASOPP may have obvious injury at intestinal mucosa at early stage (144 h), but the intestinal permeability is normal. Early enteral nutrition therapy can promote the recovery of patients, but has low correlation with intestinal barrier function improvement.
Assuntos
Nutrição Enteral , Intoxicação por Organofosfatos , Humanos , Mucosa Intestinal , Intestinos , Estudos ProspectivosRESUMO
Objective: To evaluate the efficacy and safety of rituximab combined with the modified NHL-BFM-90 protocol in childhood and adolescence with Burkitt's lymphoma (BL). Methods: A retrospective analysis of 67 untreated childhood and adolescence patients with BL was made. All patients were treated with the modified NHL-BFM-90 protocol with or without rituximab. Results: The 64 patients (95.52%) achieved complete remission (CR), 3 patients (4.48%) partial remission (PR), and the overall response rate (CR+PR) was 100%. 67 patients were followed up for a median of 44 (3-89) months. The 3 and 5-year overall survival (OS) were 92.54% and 88.98%, respectively. The 3 and 5-year progression-free survival (PFS) were all 90.34%. The 5-year OS were 100%,91.7% and 80.0% in low risk, moderate risk and high risk group, respectively, and the difference was statistically significant (P=0.048). Of the 67 patients, 55 patients (82.09%) were treated with rituximab plus chemotherapy. Compared with the 5-year OS and PFS of 74.3% and 78.6% in the chemotherapy group, the 5-year OS and PFS in the rituximab plus chemotherapy group were 95.2% and 95.5%, respectively, and the difference was statistically significant (P value was 0.021, and 0.036, respectively). Major toxicity was myelosuppression and mucositis. No treatment related death was found. Conclusions: Rituximab combined with the modified NHL-BFM-90 protocol was highly effective for children and adolescents with BL, and significantly improved long-term survival.
Assuntos
Linfoma de Burkitt , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma de Burkitt/tratamento farmacológico , Criança , Intervalo Livre de Doença , Humanos , Intervalo Livre de Progressão , Indução de Remissão , Estudos Retrospectivos , Rituximab/uso terapêutico , Resultado do TratamentoRESUMO
Objective: To investigate the awareness of preconception care among women of child-bearing age with type 1 diabetes (T1DM) and their self-management status, in order to provide evidence for establishment of management pathway for women with T1DM in pregnancy in China. Methods: This cross-sectional survey recruited female participants of child-bearing age from the cohort of Guangdong Type 1 Diabetes Translational Medicine Study conducted between June 2011 and December 2017. The participants were asked to fill out a questionnaire on the awareness of preconception care, their frequency of self-monitoring of blood glucose (SMBG) and other related variables. Chi-squared test or chi-squared test for trend was used in comparisons of categorical variables, and logistic regression analysis was performed to assess associated factors. Results: Totally, 441 women of child-bearing age with T1DM were investigated. The results show that their awareness of preconception care was poor (15.42%, 68/441). Higher educational level (χ(2trend)=3.990, P=0.046), experience of post-diabetes education evaluation (P<0.001), and better coverage of different modules in diabetes education (survival skills: χ(2)=7.525, P=0.004; basic knowledge: χ(2)=8.598, P=0.002; advanced knowledge: P<0.001) were associated with better awareness of preconception care. The average frequency of SMBG in these participants was 0.29 (0.14, 2.00) times per day, and only 8.5% (37/435) of them reached the frequency (≥4 times per day) recommended by guidelines. Moreover, 21.1% (92/435) of them hardly ever performed SMBG. Conclusion: Child-bearing age women with T1DM in Gunangdong had poor awareness of preconception care, with a much lower SMBG frequency than recommendation.
Assuntos
Diabetes Mellitus Tipo 1 , Conscientização , Automonitorização da Glicemia , China , Estudos Transversais , Diabetes Mellitus Tipo 1/complicações , Feminino , Humanos , Gravidez , Complicações na GravidezRESUMO
Objective: To investigate the relationship between insulin resistance (IR) and dyslipidemia in adults with type 1 diabetes (T1DM) and provide more insights on diabetes-related cardiovascular disease management. Methods: A cross-sectional study recruiting patients from Guangdong T1DM Translational Study cohort was conducted between 2011 and 2017. The patients aged ≥18 years, with a diabetes duration of ≥1 year were enrolled in the study. Plasma lipid profile data of eligible patients, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were collected and their relationships with insulin resistance were analyzed. IR in these adults with T1DM was estimated by glucose disposal rate (eGDR) calculated by a model published previously. Patients with eGDR lower than 25 percentiles were grouped as severe IR, otherwise non-severe IR. Results: In total, 499 eligible patients were studied, among which 274 were women (54.9%). The level of eGDR was 8.43 (6.11, 10.63) mg kg(-1) min(-1) and the overall incidence of lipid disorders was 65.3% (326/499) in the study population. The result showed that eGDR was correlated with TC, TG, HDL-C and LDL-C (r=-0.163, -0.303, 0.170 and -0.150, respectively, all P<0.05). After adjusting for gender, age and diabetes duration, eGDR was still associated with TG, TC and LDL-C (all P<0.05). Stepwise multiple linear regression analysis showed that gender (female), elevated TC and declined HDL-C were independent factors associated with the severity of IR (t=5.651, 5.823 and 2.908, respectively, all P<0.05). Conclusions: IR is associated with dyslipidemiain in adults with T1DM. Elevated TC and decreased HDL-C are independent associated factors for insulin resistance.
Assuntos
Diabetes Mellitus Tipo 1 , Dislipidemias , Resistência à Insulina , Adolescente , Adulto , Estudos Transversais , Diabetes Mellitus Tipo 2 , Feminino , Humanos , Masculino , TriglicerídeosRESUMO
The ocnus (ocn) gene encodes a protein abundant in the testes, implying its role in testis development. When Drosophila melanogaster is infected with the endosymbiont wMel Wolbachia, which affects the spermatogenesis of its hosts, ocn is downregulated in the third-instar larval testes, suggesting a role of ocn in spermatogenesis. In this study, we knocked down ocn in the testes and found that the hatch rates of embryos derived from ocn-knockdown males were significantly decreased, and 84.38% of the testes were much smaller in comparison to controls. Analysis of the smaller testes showed no germ cells but they had an extended hub. Using RNA-sequencing (RNA-Seq), we identified 69 genes with at least a twofold change (q-value < 5%) in their expression after ocn knockdown; of these, eight testes-specific and three reproduction-related genes were verified to be significantly downregulated using quantitative reverse transcription-PCR. Three genes (orientation disruptor, p24-2 and CG13541) were also significantly downregulated in the presence of Wolbachia. Furthermore, 98 genes were not expressed when ocn was knocked down in testes. These results suggest that ocn plays a crucial role in male germ cell development in Drosophila, possibly by regulating the expression of multiple spermatogenesis-related genes. Our data provide important information to help understand the molecular regulatory mechanisms underlying spermatogenesis.
Assuntos
Proteínas de Drosophila/fisiologia , Drosophila melanogaster/fisiologia , Regulação da Expressão Gênica , Monoéster Fosfórico Hidrolases/fisiologia , Espermatogênese , Animais , Fertilidade , Masculino , Testículo/crescimento & desenvolvimento , TranscriptomaRESUMO
To retrospectively analyze the safety and efficacy of low dose rituximab regimen in patients with Epstein-Barr virus (EBV) infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Among 12 cases, 11 achieved complete remission (CR), 1 with partial remission (PR). Patients received 15 infusions with a median of 2.5(1-4) in each. The EBV DNA negative transformation period was 5-25 days with median 12 days. Low dose rituximab could be an alternative choice in patients with EBV infection after allo-HSCT.
Assuntos
Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/virologia , Rituximab/administração & dosagem , Viremia/tratamento farmacológico , Adulto , Anticorpos Monoclonais Murinos/efeitos adversos , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos Clínicos , DNA Viral/sangue , Cálculos da Dosagem de Medicamento , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Indução de Remissão , Estudos Retrospectivos , Rituximab/uso terapêutico , Condicionamento Pré-Transplante , Transplante Homólogo , Viremia/sangue , Viremia/imunologia , Viremia/virologia , Ativação Viral/efeitos dos fármacosRESUMO
Objective: To explore the influence of patatin-like phospholipase domain containing-3 (PNPLA3) wild type 148I/I and mutant type 148M/M on HepG2 cell proliferation and the relative mechanisms. Methods: HepG2 cell line stably overexpressing PNPLA3 148I/I, 148M/M and negative control (NC) were set up. Cell counting kit-8 (CCK8) assay was used to measure cell viability. Edu assay was used to determine the ability of cell proliferation. Western blot was used to detect the protein levels in the phosphatidylinositol 3-kinases (PI3K) pathway. Enzyme-linked immunosorbent assay (ELISA) was used to detect proliferation-related PNPLA3 metabolites[arachidonic acid (AA) and lysophosphatidic acid (LPA)]. Quantitative real-time PCR was used to detect the expression level of prostaglandin G/H synthase 2 (PTGS2) and proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) associated with PNPLA3. Results: The cell viability of overexpression of PNPLA3 148M/M group was about 1/3 times higher than that of overexpression of PNPLA3 148I/I group, and the difference was statistically significant[(98.02±1.29)% vs (71.51±2.89)%, P<0.001]. There was no significant difference between overexpression of PNPLA3 148M/M group and negative control group[(98.02±1.29)% vs (100±2.61)%, P=0.181]. The proliferative activity of overexpression of PNPLA3 148M/M group was about 1/3 times higher than that of overexpression of PNPLA3 148I/I group, and the difference was statistically significant(46.46±1.83 vs 35.96±2.65, P=0.001). There was no significant difference between overexpression of PNPLA3 148M/M group and negative control group(46.46±1.83 vs 46.64±7.33, P=0.965). The PGC1α mRNA expression, total PI3K, PThr-308AKT, PSer2448-mammalian target of rapamycin (PSer2448-mTOR) and PGC1α protein expression levels in the overexpression of PNPLA3 148M/M group were higher than those in the overexpression of PNPLA3 148I/I group, but there were no significant differences in AA and LPA levels, as well as PTGS2 mRNA expression levels. Conclusion: PNPLA3 148M/M cell proliferation was stronger than PNPLA3 148I/I.
Assuntos
Hepatócitos , Proliferação de Células , Genótipo , Lipase , Fígado , Proteínas de Membrana , Fosfatidilinositol 3-Quinases , Fosfolipases A2RESUMO
Objective: To explore the factors associated with glycemic control in children and adolescents with type 1 diabetes mellitus (T1DM) treated with continuous subcutaneous insulin infusion (CSII). Methods: Subjects were enrolled from the Guangdong Type 1 Diabetes Translational Medicine Study between June 2011 and August 2017. Patients with T1DM aged less than 18 years and treated with CSII for at least 6 months were included. Demographic data and clinical information on self-monitoring of blood glucose (SMBG), glycosylated hemoglobin (HbA1c) and insulin treatment were collected. Participants were categorized based on HbA1c levels as sufficient control group (HbA1c<7.5% ) and insufficient control group ( HbA1c≥7.5%). A multivariate logistic regression model was used to examine the factors associated with glycemic control. Results: A total of 142 participants (76 females, 66 males) with a median age of 13.0 (9.9, 15.0) years and a median disease duration of 3.0 (1.6, 5.0) years were enrolled. HbA1c was (8.2±2.0)% and 41.55%(59/142) of patients achieved the target for HbA1c. The frequency of SMBG was 5.0 (2.0, 8.0) and 3.0 (1.0, 4.0) tests per day (P<0.001), and the frequency of hypoglycemia was 2.0 (0.8, 4.0) and 1.0 (0, 2.0) times per week (P=0.003) in sufficient control group and insufficient control group, respectively. Sufficient glycemic control (HbA1c <7.5%) was associated with the frequency of SMBG (OR=1.238, 95% CI: 1.088-1.409, P=0.001). Conclusion: A higher frequency of SMBG is one of the key factors to achieve sufficient glycemic control among children and adolescents with T1DM treated with CSII.
Assuntos
Glicemia , Diabetes Mellitus Tipo 1 , Adolescente , Automonitorização da Glicemia , Criança , Feminino , Hemoglobinas Glicadas , Humanos , Hipoglicemiantes , Insulina , Sistemas de Infusão de Insulina , MasculinoRESUMO
It is known that the autophagy-related protein 1 (ATG1) plays critical roles in the regulation of autophagy in mammals and yeast, whereas the function of ATG1 in lepidopteran insects is not well elucidated. Here Spodoptera litura ATG1 (SlATG1) and its interactions with other ATG proteins were characterized. Alternative splicing of SlAtg1 produced at least four transcript variants. Over-expression and RNA interference knockdown of SlAtg1 demonstrated that SlATG1 enhanced autophagy. SlATG1A-Green fluorescent protein (GFP) tagged localized in the cytoplasm and formed some punctuate dots, which were colocalized with red fluorescent protein mCherry tagged Spodoptera exigua ATG5 (SeATG5). SlATG1A-GFP over-expression reduced the nuclear abundance of mCherry-SeATG5 but increased its cytoplasmic abundance. Pull-down, co-immunoprecipitation and bimolecular fluorescence complementation assays showed that SlATG1A bound to SeATG5 through the N-terminus of SlATG1A. The over-expression of FLAG epitope tagged SlATG1A significantly increased the accumulation of the cleaved GFP from GFP-SeATG5, suggesting the enhanced degradation of GFP-SeATG5. In addition, we confirmed that the interactions of SlATG1 with other autophagy-related proteins were conserved. These results provide the first evidence that ATG1 interacts with ATG5 and enhances its degradation in lepidopteran insect cells, which may have important physiological functions.
Assuntos
Proteína 5 Relacionada à Autofagia/metabolismo , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Spodoptera/metabolismo , Animais , Autofagia , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética , Sequência de Bases , Dados de Sequência Molecular , Análise de Sequência de DNA , Spodoptera/genéticaRESUMO
Prevalence of swine respiratory disease causes poor growth performance in and serious economic losses to the swine industry. In this study, a categorical trait of enzootic pneumonia-like (EPL) score representing the infection gradient of a respiratory disease, more likely enzootic pneumonia, was recorded in a herd of 332 Chinese Erhualian pigs. According to their EPL scores and the disease effect on weight gains, these pigs were grouped into controls (EPL score ≤ 1) and cases (EPL score > 1). The weight gain of the case group reduced significantly at days 180, 210, 240 and 300 as compared to the control group. The heritability of EPL score was estimated to be 0.24 based on the pedigree information using a linear mixed model. All 332 Erhualian pigs and their nine sire parents were genotyped with Illumina Porcine 60K SNP chips. Two genome-wide association studies were performed under a generalized linear mixed model and a case-control model respectively. In total, five loci surpassed the suggestive significance level (P = 2.98 × 10-5 ) on chromosomes 2, 8, 12 and 14. CXCL6, CXCL8, KIT and CTBP2 were highlighted as candidate genes that might play important roles in determining resistance/susceptibility to swine EP-like respiratory disease. The findings advance understanding of the genetic basis of resistance/susceptibility to respiratory disease in pigs.
Assuntos
Predisposição Genética para Doença , Doenças Respiratórias/veterinária , Doenças dos Suínos/genética , Suínos/genética , Animais , Cruzamento , China , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Modelos Lineares , Masculino , Modelos Genéticos , Linhagem , Fenótipo , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Doenças Respiratórias/genéticaRESUMO
Chinese indigenous pigs display marked genetic and phenotypic differences compared with western commercial pigs. In this study, we tested the association between 660K SNPs and longissimus muscle fatty acid composition traits in Chinese Erhualian (n = 331) and Bamaxiang (n = 315) pigs based on a customized 1.4 million SNP array. We identified a total of 64 significant associations for 20 fatty acid composition traits at the p-value threshold of 1 × 10-6 among which 42 associations in low linkage disequilibrium (r2 < .2) with previously reported loci were considered novel. We substantially improved the strength and precision of the associations at four previously detected loci near FADS2, ELOVL7, ELOVL6 and FASN genes, facilitating follow-up candidate gene studies. Moreover, we also identified loci near ABCD2, ACSBG1, ELOVL5, HPGDS, DAGT2, ACAD10 and ACSL1 genes with function relevant to metabolism of fatty acids. In this study, valuable genetic variants and candidate genes associated with fatty acid composition traits were identified in Erhualian and Bamaxiang pigs. Some identified loci could be used to improve pork nutrition in pig breeding practice. Using the SNP array with higher marker density and less ascertainment bias improved QTL detection power and precision in Chinese indigenous pigs.
Assuntos
Ácidos Graxos/genética , Estudo de Associação Genômica Ampla , Músculo Esquelético/química , Locos de Características Quantitativas , Sus scrofa/genética , Animais , Ácidos Graxos/análise , Genótipo , Fenótipo , Polimorfismo de Nucleotídeo ÚnicoRESUMO
To retrospectively analyze the safety and efficacy of low dose subcutaneous decitabine regimen in patients with acute myeloid leukemia (AML) and intermediate- or higer-risk myelodysplastic syndrome (MDS). Of 6 AML cases, 2 achieved complete remission (CR), 2 with partial remission(PR), 1 with stable disease(SD), 1 with progressive disease(PD). As to the 8 MDS patients, one achieved CR and 6 with hematologic improvement (HI), 1 case SD. Low dose subcutaneous decitabine regimen could be an alternative choice of older AML or MDS patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Azacitidina/análogos & derivados , Leucemia Mieloide Aguda/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Azacitidina/administração & dosagem , Azacitidina/uso terapêutico , Decitabina , Humanos , Pessoa de Meia-Idade , Pacientes , Indução de Remissão , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Objective: To describe the insulin regimens and their associations with glycemic control and to explore factors associated with intensive insulin therapy. Methods: Patients with type 1 diabetes (T1DM) were recruited from Guangdong Type 1 Diabetes Mellitus Translational Medicine Study which was conducted in 16 centers in Guangdong province. The demographic and clinical data were collected. Patients were grouped according to different insulin regimens: insulin pump (R1), basal insulin plus regular insulin or short-acting insulin (R2), insulin injection 1-3 times per day (R3). Distribution of insulin regimens and the relationships between insulin regimens and hemoglobin A1c (HbA1c) were described. Multivariate logistic regression was used to identify factors associated with intensive insulin therapy. Results: A total of 1 421 patients with the age of 27.8 (19.4, 38.3) years and a duration of T1DM of 3.3 (0.5, 7.1) years were recruited. There was 12.3% of patients in R1 (n=175), 35.5% in R2 (n=504), and 52.2% in R3 (n=742), respectively. HbA1c was 8.0 (6.8, 9.3)%, 8.9 (7.1, 11.8)%, and 9.2 (7.5, 11.4)% in R1, R2, R3, respectively, and it was associated with insulin regimens (P<0.001). HbA1c target rate was 32.3%, 21.1%, 17.8% in R1, R2, R3, respectively (P=0.002). Older age (OR=1.01, P=0.027), higher education level (college or above) (OR=1.56, P=0.003), and higher household income (>30 000 yuan per year per person)(OR=1.45, P=0.009) were associated with intensive insulin therapy in adult patients. Conclusions: The study suggested that insulin therapy need to be optimized in patients with T1DM. The optimization of insulin regimens and diabetes education may be helpful for improvement of glycemic control.
Assuntos
Diabetes Mellitus Tipo 1 , Adulto , Glicemia , Hemoglobinas Glicadas , Humanos , Hipoglicemiantes , Insulina , Sistemas de Infusão de Insulina , Modelos Logísticos , Adulto JovemRESUMO
To detect Salmonella more efficiently and isolate strains more easily, a novel and simple detection method that uses an enrichment assay and two chromogenic reactions on a chromatography membrane was developed. Grade 3 chromatography paper is used as functionalized solid phase support (SPS), which contains specially optimized medium. One reaction for screening is based on the sulfate-reducing capacity of Salmonella. Hydrogen sulfide (H2S) generated by Salmonella reacts with ammonium ferric citrate to produce black colored ferrous sulfide. Another reaction is based on Salmonella C8 esterase that is unique for Enterobacteriaceae except Serratia and interacts with 4-methylumbelliferyl caprylate (MUCAP) to produce fluorescent umbelliferone, which is visible under ultraviolet light. A very low detection limit (10(1) CFU ml(-1)) for Salmonella was achieved on the background of 10(5) CFU ml(-1) Escherichia coli. More importantly, testing with more than 1,000 anal samples indicated that our method has a high positive detection rate and is relatively low cost, compared with the traditional culture-based method. It took only 1 day for the preliminary screening and 2 days to efficiently isolate the Salmonella cells, indicating that the new assay is specific, rapid, and simple for Salmonella detection. In contrast to the traditional culture-based method, this method can be easily used to screen and isolate targeted strains with the naked eye. The results of quantitative and comparative experiments showed that the visual detection technique is an efficient alternative method for the screening of Salmonella spp. in many applications of large-sized samples related to public health surveillance.