RESUMO
Objective: To study the clinical efficacy of chimeric antigen receptor T-cell (CART) treatment followed by a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with B-cell acute lymphoblastic leukemia (ALL) who relapsed following the first HSCT. Methods: Retrospective analysis of the clinical characteristics and prognosis of 41 patients with B-cell ALL who received a second allo-HSCT from October 2015 to June 2020 in Hebei Yanda Lu Daopei Hospital. After the first HSCT, all patients received CD19-CART, or CD22-CART treatment following a relapse of bone marrow morphology or extramedullary leukemia. Results: A total of 41 patients (male, 21; female, 20) were included in this study. The median age at the second HSCT was 16 (3-46) years. There were 31 cases of bone marrow recurrence (75.6%) , 5 cases of extramedullary recurrence (12.2%) , and 5 cases of bone marrow and extramedullary recurrences (12.2%) . After relapse, 35 patients (85.4%) received CD19-CART treatment, 2 patients received CD22-CART treatment (4.9%) , and 4 patients received CD19-CART and CD22-CART treatments (9.8%) . The expected 3-year overall survival (OS) , leukemia-free survival, cumulative relapse incidence, and non-relapse mortality (NRM) of patients after the second HSCT were 48.9% (95%CI 23.0%-70.6%) , 41.8% (95%CI 17.3%-64.9%) , 8.8% (95%CI 2.9%-26.4%) , and 51.1% (95%CI 31.2%-83.6%) , respectively. The 1-year OS of patients who relapsed ≤6 months and >6 months after the first HSCT were 45.0% (95%CI 12.7%-73.5%) and 75.0% (95%CI 51.4% -88.8%) (P=0.017) , respectively. Conclusion: CART bridging in the second HSCT enables some B-cell ALL patients who relapsed after the first HSCT to achieve long-term survival. However, because of the high NRM, further modifications could help improve the outcome.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Linfócitos B , Feminino , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Recidiva , Estudos RetrospectivosRESUMO
Objective: To compare the efficacy of haplotype hematopoietic stem cell transplantation (HIDT) and sibling matched hematopoietic stem cell transplantation (MSDT) in the treatment of complete remission (CR) acute T-lymphoblastic leukemia (T-ALL) . Methods: We retrospectively analyzed the clinical characteristics and outcomes of 98 patients who underwent HSCT in Hebei Yanda Ludaopei hospital with HID (n=81) or ISD (n=17) between May 2012 and May 2016. Results: The incidence of grades 2-4 and 3-4 acute-versus-host disease 100 days after HSCT were 51.9% (95% Confidence interval [CI] 42.0%-64.0%) vs 29.4% (95% CI 14.1%-61.4%) (P=0.072) and 9.8% (95% CI 5.1%-19.1%) vs 11.8% (95% CI 3.2%-43.3%) (P=1.000) for HIDT and MSDT. The 100-day cumulative incidences of CMV and EBV viremia were 53.1% (95% CI 43.3%-65.2%) vs 29.4% (95% CI 14.1%-61.4%) (P=0.115) and 35.8% (95% CI 26.8%-47.9%) vs11.8% (95% CI 3.2%-43.3%) (P=0.048) . The 5-year overall survival, leukemia-free survival, cumulative incidences of relapse, and no-relapse mortality were 60.5% (95% CI 5.4%-49.0%) vs 68.8% (95% CI 11.8%-40.0%) (P=0.315) , 58.0% (95% CI 5.5%-46.5%) vs 68.8% (95% CI 11.8%-40.0%) (P=0.258) , 16.1% (95% CI 9.8%-26.4%) vs 11.8% (95% CI 3.2%-43.3%) (P=0.643) , 25.9% (95% CI 17.9%-37.5%) vs 19.4% (95% CI 6.9%-54.4%) (P=0.386) for HIDT and MSDT, respectively. Conclusion: HID could be a valid alternative donor for patients with T-ALL in CR lacking an identical donor.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , Estudos Retrospectivos , Irmãos , Transplante de Células-Tronco , Linfócitos TRESUMO
Objective: To evaluate the association of TP53 mutations with the clinical outcomes of Ph-negative B-ALL following allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Total 300 patients with Ph-negative B-ALL who underwent allo-HSCT at the Hebei Yanda Ludaopei Hospital from May 2012 to May 2017 were retrospectively analyzed; their clinical characteristics, TP53 gene mutation type, and association between TP53 mutations and transplantation outcomes, including leukemia-free survival (LFS) , overall survival (OS) , non-relapse mortality (NRM) , relapse, and GVHD, were evaluated. Results: Total 23 patients had TP53 mutations; all the TP53 mutations affected P53'DNA-binding domain. The 5-year-LFS, OS, and RI were 34.8% and 62.3% (P=0.001) , 41.9% and 65.1% (P=0.020) , and 47.8% and 14.8% (P=0.000) , respectively, for TP53 mutations and wild-type TP53 patients. However, there were no significant differences in NRM and GVHD. Multivariate analysis showed that TP53 mutations remained adverse prognostic factors for LFS, OS, and RI after allo-HSCT. Conclusion: Some patients with TP53 mutations can achieve long-term survival with allo-HSCT. TP53 mutations are adverse prognostic factors for Ph-negative B-ALL patients who undergo allo-HSCT.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Proteína Supressora de Tumor p53/genética , Doença Aguda , Humanos , Mutação , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Prognóstico , Estudos Retrospectivos , Transplante Homólogo , Resultado do TratamentoRESUMO
Objective: To study the clinical results and prognostic factors for allo-HSCT of Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL) in complete remission (CR) in the era of tyrosine kinase inhibitors (TKI) . Methods: We performed a retrospective analysis of the clinical characteristics of 116 patients with Ph(+)ALL who underwent allo-HSCT while in CR. Results: The study population included 72 men and 44 women. The median patient age was 20 years (4-64 years) . The patients received sibling-identical donor (n=21) , haplo (n=77) , and unrelated donor (n=18) HSCT. The overall survival (OS) rate at 5 years was 73.2% (95% CI 63.8% -80.5% ) . In particular, the 5-year OS can reach 87.5% when the time from diagnosis to transplant is <180 days. The 5-years DFS was 61.4% (95% CI 51.8% -69.7% ) , the 5-year molecular and morphology cumulative relapse incidence was 18.5% (95% CI 12.6% -27.3% ) , and the 5-year TRM was 19.9% (95% CI 13.8% -28.7% ) . A multivariate analysis showed that an age range of 15-39 years (HR=2.730, P=0.044) , time from diagnosis to HSCT ≥ 180 days (HR=4.534, P=0.010) , and â ¢-â £grade aGVHD (HR=7.558, P=0.000) were significantly associated with an inferior overall survival. Limited cGVHD subgroup had better OS (HR=0.300, P=0.034) . Sex, WBC count at diagnosis, type of BCR-ABL fusion genes, somatic gene mutations, CR(1) or >CR(1), MRD negative or positive, conditioning regimen based on TBI or Bu, conditioning intensity, donor source, GVHD prophylactic proposal using cyclosporine or tacrolimus, presence/absence of CMV viremia, and presence/absence of EBV viremia were not significantly different in terms of the OS and DFS. Conclusion: Factors influencing the overall survival of Ph(+) ALL patients who underwent allo-HSCT in CR in the TKI era include age, time form diagnosis to HSCT, and aGVHD severity.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Prognóstico , Inibidores de Proteínas Quinases , Estudos Retrospectivos , Adulto JovemRESUMO
Objective: To investigate the distribution of tear film lipid layer thickness (LLT) and the relationship between symptoms and signs of dry eye and tear film LLT in the population of Taishitun Community in Beijing. Methods: A cross-sectional study. From May 2016 to August 2016, three streets of Taishitun Community were randomly selected as survey districts and 540 persons were taken as investigation subjects. Every participant completed 6 items of dry eye examinations as follows: questionnaire (Ocular Surface Disease Index, OSDI), measurement of tear film LLT, tear film break-up time (TBUT), corneal and conjunctival staining, Schirmerâ test and the infrared meibomian photography. According to their age, all participants were divided into four groups: junior group (<18 years old), youth group (18 to 40 years old), middle-aged group (41 to 59 years old) and the elderly group (over 60 years old). With the OSDI criteria, no dry eye symptom group (score, <12 points), mild to moderate dry eye symptom group (score, 12 to 32) and severe dry eye symptom group (score, 33-100) were included. With the statistical methods of variance analysis and multivariate Logistic regression analysis, distribution of the variables of LLT and the relationship between dry eye symptoms and LLT were studied. Results: A total of 473 residents finally participated in this study, and the response ratio was 87.6%. The values of LLT were normally distributed. The average LLT was (59.87±18.50) nm [(60.16±19.15) nm in males and (59.67±18.57) nm in females], and the comparison of LLT with different genders was not statistically significant (t=0.198, P=0.843). The tear film LLT of four different age groups had statistical significance (F=15.092, P<0.05), and increased with age [(56.10±18.33) nm in the junior group, (54.60±16.29) nm in the youth group, (60.61±19.18) nm in the middle-aged group and (73.25±14.58) nm in the elderly group]. The LLT was inversely proportional to the severity of dry eye symptoms. With a thinner LLT, the symptoms of the subjects turned severe. In the elderly with different degrees of symptoms, the LLT was significantly different (F=0.019, P<0.05), while in the youth and middle-aged groups with different degrees of symptoms, the LLT was not significantly different (F=0.096, P>0.05. F=0.538, P>0.05). In the OSDI symptom questionnaire, only blurred vision and decreased visual acuity were related to the tear film LLT (P<0.05). There was no significant correlation between the TBUT, Schirmerâ test result, meibomian gland loss rate and the tear film LLT (P>0.05). Conclusions: In Taishitun Community of Beijing, the values of tear film LLT had a normal distribution. The LLT was positively correlated with age, but inversely correlated with the severity of the symptoms of dry eye. There was no significant correlation between the LLT and the TBUT, Schirmerâ test result and meibomian gland loss rate.(Chin J Ophthalmol, 2017, 53: 495-501).
Assuntos
Síndromes do Olho Seco , Lipídeos , Lágrimas , Adolescente , Adulto , Idoso , Pequim/epidemiologia , Estudos Transversais , Síndromes do Olho Seco/epidemiologia , Estudos Epidemiológicos , Feminino , Humanos , Lipídeos/análise , Masculino , Glândulas Tarsais , Pessoa de Meia-Idade , Lágrimas/química , Adulto JovemRESUMO
Objective: To investigate three different types of donor hematopoietic stem cell transplantation (HSCT) for intermediate and high-risk myelodysplastic syndrome (MDS) . Methods: Between August 2001 and May 2015, 167 consecutive patients with MDS in intermediate and high-risk who underwent allogeneic HSCT were analyzed retrospectively. Results: With the median follow up of 60 (12-177) months, The total 5-year DFS was 67.8% (95%CI 60.0%-75.6%) . Among three different types of donor, 5-year DFS rates were 68.0% (95%CI 54.1%-81.9%) in MSD-HSCT vs 77.4% (95%CI 62.1%-92.7%) in MUD-HSCT vs 64.0% (95% CI 52.4%-75.6%) in Haplo-HSCT (P=0.632) , respectively. Univariate analysis showed that median disease course before HSCT was the influencing factor of DFS (P=0.018) . Five-year relapse and TRM had no correlation with the above-mentioned factor. Conclusions: Haplo-HSCT for intermediate and high-risk MDS achieved similar effect produced by MUD or MSD, Haplo-HSCT could be used as an important alternative donor. allo-HSCT must be performed on intermediate and high-risk MDS patients as early as possible after diagnosis.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas , Doença Crônica , Humanos , Recidiva , Estudos Retrospectivos , Fatores de Risco , Doadores de Tecidos , Condicionamento Pré-Transplante , Transplante HomólogoRESUMO
OBJECTIVE: MicroRNAs are reported to play key roles in regulating the main risk factors for osteoarthritis (OA) chondrogenesis. In the current study, we focused on miR-138, which has never been explored in OA. PATIENTS AND METHODS: The expression of miR-138 and p65 was explored in the cartilage tissues of OA patients and compared with those of normal controls. We then explored the effects of miR-138 on NF-κB signaling activation in both human OA chondrocytes and chondrogenic SW1353 cells in the presence of 10 nM TNFα. The protein levels of p65, COX-2 and IL6 were determined using Western blot analysis. To validate the target gene of miR-138, a dual luciferase reporter assay was performed. RESULTS: The level of miR-138 was markedly reduced in the OA cartilage tissues compared with those of normal controls. Real-time PCR analysis demonstrated that the level of miR-138 decreased after TNFα treatment for 3, 6, and 12 h in the normal chondrocytes and OA chondrocytes. Furthermore, overexpression of miR-138 suppressed the protein levels of p65, COX-2 and IL6 in human OA chondrocytes and chondrogenic SW1353 cells. A dual luciferase reporter assay demonstrated that miR-138 significantly suppressed the relative luciferase activity of pmirGLO-p65-3'UTR. More importantly, treatment with TNFα significantly enhanced the protein levels of p65, COX-2 and IL6. However, overexpression of miR-138 could partially abolish such effects. CONCLUSIONS: We demonstrated that reduced miR-138 expression enhanced the destruction of the cartilage tissues among OA patients, mainly through targeting p65.
Assuntos
MicroRNAs/fisiologia , Osteoartrite/prevenção & controle , Fator de Transcrição RelA/genética , Idoso , Progressão da Doença , Humanos , MicroRNAs/análise , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/fisiologiaRESUMO
Objective: To investigate the effect of minimal residual disease (MRD) monitoring by multiparameter flow cytometry (MFC) pre-conditioning on prognosis of acute myeloid leukemia in first complete remission (CR(1)-AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) , and to explore the value of MRD monitoring by MFC in the prognosis evaluation on allo-HSCT in CR(1)-AML. Methods: Between April 2012 and March 2015, consecutive 186 patients with CR(1)-AML who underwent allo-HSCT were analyzed retrospectively. MRD in BM before conditioning was detected by eight-color MFC. Any level of residual disease was considered to be MRD positive. Results: â Of 186 patients, MRD was negative in 151 patients, positive in 35 patients (<1% in 25 patients and 1% to 3% in 10 patients) . â¡ With the median follow up of 18 (5-41) months, two-year DFS was 80.0% (95%CI 68.5%-92.3%) . Univariate analysis showed that MRD positive patients had lower DFS[62.9% (95%CI 50.6%-75.2%) vs 88.9% (95%CI 76.6%-100.0%) , P<0.001], higher relapse[11.4% (95%CI 4.1%-29.0%) vs 3.3% (95% CI 0.6%-20.9%) , P=0.003] and higher NRM [25.7% (95% CI 8.1%-43.3%) vs 7.9% (95% CI 1.3%-26.5%) , P=0.001] after HSCT compared with that of MRD negative patients. Secondary AML showed lower DFS than primary AML [60.0% (95% CI 42.4%-76.6%) vs 86.0% (95% CI 68.4%-100.0%) , P=0.004]. â¢Multivariate analysis indicated that MRD positive pre-HSCT was the independent risk factor on DFS [HR=4.565 (95%CI 2.918-9.482) , P<0.001], relapse [HR=5.854 (95%CI 1.538-22.288) , P=0.010] and NRM [HR=3.379 (95%CI 1.361-8.391) , P=0.009] after allo-HSCT in CR(1)-AML. Conclusion: MRD positive pre-conditioning was the only negative impact factor for patients with CR(1)-AML after allo-HSCT. MRD by MFC can be used to assess the prognosis of CR(1)-AML after allo-HSCT.
Assuntos
Neoplasia Residual , Doença Crônica , Citometria de Fluxo , Transplante de Células-Tronco Hematopoéticas , Humanos , Fator de Impacto de Revistas , Leucemia Mieloide Aguda , Prognóstico , Recidiva , Estudos Retrospectivos , Fatores de Risco , Transplante HomólogoRESUMO
Based on the one-dimensional tight-binding Su-Schrieffer-Heeger (SSH) model, and using the molecular dynamics method, we discuss the dynamics of electron and hole polarons propagating along a polymer chain, as a function of the distance between side radicals and the magnitude of the transfer integrals between the main chain and the side radicals. We first discuss the average velocities of electron and hole polarons as a function of the distance between side radicals. It is found that the average velocities of the electron polarons remain almost unchanged, while the average velocities of hole polarons decrease significantly when the radical distance is comparable to the polaron width. Second, we have found that the average velocities of electron polarons decrease with increasing transfer integral, but the average velocities of hole polarons increase. These results may provide a theoretical basis for understanding carriers transport properties in polymers chain with side radicals.
Assuntos
Polímeros/química , Elétrons , Simulação de Dinâmica Molecular , Estrutura MolecularRESUMO
Objective: To analyze the effect of NCCN (2015) risk stratification on prognosis of patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Retrospective analysis of 258 patients with AML in CR (186 cases in CR(1), 72 cases in CR(2)) who underwent allogeneic HSCT in our hospital between April 2012 and March 2015 according to NCCN (2015) risk stratification. Of them, 63 cases were classified as low risk, 112 cases intermediate risk and 83 cases high risk. Results: â With the median follow up of 18 (5-41) months, two-year disease free surviva (DFS) in 258 patients was 78.0% (95% CI 60.4%-96.6%) . Two-year DFS in AML after transplantation was 78.6% (95% CI 61.0%-96.2%) in low risk, 76.0% (95% CI 84.0%-93.6%) in intermediate risk and 80.3% (95% CI 62.7%-97.9%) (P=0.886) in high risk groups respectively. â¡Univariate analysis showed that DFS has no significant difference in patient age, the median disease course before HSCT, the WBC number at the beginning of the disease, blood routine and chromosomes examination before transplantation, extramedullary disease before transplantation, disease status before transplantation, conditioning regimen, donor type, donor and recipient sex, recipient blood type, transfused MNC number, transfused CD34(+) cell number and transfused CD3(+) cell number. DFS was significant lower in primary AML than that in secondary AML (P=0.006) and also lower in MRD positive than that in MRD negative (P=0.003) . The accumulative relapse was significant higher in CR(2) compared to that in CR(1) (P=0.046) . Accumulative non-relapse mortality (NRM) was significanlyt higher in secondary AML compared to that in primary AML (P=0.004) and also higher in MRD positive compared to that in MRD negative (P=0.010) . â¢Multivariate analysis showed that MRD positive was the only significant factor in DFS and NRM. Conclusion: Allo-HSCT treatment of AML CR patients could achieve a high efficacy, which is similar between CR(1) and CR(2) patients. There is no significant correlation between NCCN (2015) risk stratification and the prognosis of AML patients with allo-HSCT treatment. Pre-conditioning MRD status monitored by multiparameter flow cytometry was the only impact factor on DFS and NRM in allo-HSCT for CR-AML patients.
Assuntos
Leucemia Mieloide Aguda , Doença Crônica , Citometria de Fluxo , Transplante de Células-Tronco Hematopoéticas , Humanos , Fator de Impacto de Revistas , Prognóstico , Recidiva , Estudos Retrospectivos , Risco , Doadores de Tecidos , Transplante HomólogoRESUMO
BACKGROUND: Endoscopic submucosal dissection (ESD) has been developed to allow en bloc resection of early neoplasia of the gastrointestinal tract, including colorectal tumors. The aim of the present study was to evaluate the safety and efficacy of ESD for laterally spreading tumors (LSTs) in the rectum with diameters of 40 mm or more. METHODS: Between January 2010 and October 2014, 35 patients with a total of 36 LSTs of the rectum measuring ≥40 mm were included in this study. Clinical and pathological characteristics and clinical outcomes were examined and analyzed. RESULTS: The mean operating time was 125.8 ± 61.4 min, and the mean size of the tumors was 59.4 ± 19.8 mm. The rate of en bloc resection and en bloc R0 resection were 91.7 % (33/36) and 88.9 % (32/36), respectively. Perforation occurred in three patients (8.6 %) and was managed conservatively. Postoperative bleeding occurred in one patient (2.9 %) and was treated by endoscopic hemostasis. Excluding five patients, who either underwent additional surgery (n = 1) or were lost to follow-up (n = 4), two patients in our cohort (6.7 %) presented with recurrence of a small adenoma. The remaining patients (n = 28) were free of recurrence during a mean follow-up period of 18.7 ± 4.2 months (range 12-43 months). CONCLUSIONS: Our results indicated that ESD is an effective and safe therapeutic option with high curative rates for LSTs in the rectum ≥40 mm. To prove its long-term efficacy, a large multicenter prospective study is required.
Assuntos
Adenoma/cirurgia , Carcinoma in Situ/cirurgia , Ressecção Endoscópica de Mucosa , Perfuração Intestinal/etiologia , Recidiva Local de Neoplasia , Hemorragia Pós-Operatória/etiologia , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Adenoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma in Situ/patologia , Intervalo Livre de Doença , Ressecção Endoscópica de Mucosa/efeitos adversos , Feminino , Hemostase Endoscópica , Humanos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Neoplasia Residual , Duração da Cirurgia , Hemorragia Pós-Operatória/terapia , Carga TumoralRESUMO
OBJECTIVES: To determine whether amlodipine/valsartan/hydrochlorothiazide single pill combination (SPC) is associated with improved persistence, adherence and reduced healthcare utilization and costs compared to the corresponding free combination (FC). METHODS: Adult (≥18 years) patients covered by commercial and Medicare Supplemental insurance in the Truven MarketScan database with hypertension (HTN) diagnosis between October 2009 and December 2011 were included. At least two filled prescriptions for the SPC cohort or two periods of minimum 15 days of concurrent use of amlodipine, valsartan and hydrochlorothiazide (HCT) for the FC cohort were required. Cohorts were propensity score matched (PSM) to balance on important confounders. Outcomes included: 1) adherence (proportion of days covered [PDC] and medication possession ratio [MPR]); 2) persistence (treatment gap >30 days); 3) all-cause and HTN-specific healthcare utilization and costs at 12 months. RESULTS: After cohort matching with PSM, patients taking SPC (N = 9221) exhibited better outcomes than FC (N = 1884): higher mean adherence (85.7% vs. 77.0%), mean PDC (73.8% vs. 60.6%) and persistence (46.8% vs. 23.6%) (all p < 0.0001). Patients taking SPC were associated with higher odds of persistence (OR: 3.51; 95% CI: 3.08-4.02), MPR ≥80% (OR: 2.72; 95% CI: 2.40-3.08) and PDC ≥80% (OR: 2.88; 95% CI: 2.55-3.26). After PSM, the SPC cohort exhibited statistically significantly lower mean number of resource utilization events compared to FC. Patients in the SPC cohort also had a statistically significantly (p < 0.05) lower percentage of patients with ≥1 all-cause hospitalization (15.0% vs. 18.2%), ≥1 all-cause emergency room (ER) visits (25.7 vs. 31.4%), and ≥1 ER HTN-specific visits (9.7% vs. 14.1%). The costs incurred by SPC cohort patients were 2.8% to 41.7% numerically lower than the FC cohort, statistically significant for all-cause ER costs ($430.6 vs. $549.5, p < 0.05). CONCLUSIONS: Real-world data indicate an association of the amlodipine/valsartan/HCT SPC with improved adherence and persistence vs. FC with no difference in overall healthcare or hypertension specific costs between the cohorts.
Assuntos
Anlodipino/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Hidroclorotiazida/administração & dosagem , Valsartana/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Combinação de Medicamentos , Feminino , Hospitalização , Humanos , Hipertensão/tratamento farmacológico , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Estudos RetrospectivosRESUMO
Infectious bronchitis virus (IBV) can multiply effectively in chick embryo kidney (CEK) cells after adapting to the chick embryo. To investigate the dynamic changes in IBV load in the supernatant of primary CEK cells, we developed an SYBR Green I-based real-time polymerase chain reaction assay to quantify nucleic copy numbers of the IBV-Sczy3 strain. The 20, 54, and 87th generations of CEK-adapted IBV-Sczy3 strains were used to infect CEK cells, and then nucleic copy numbers in the samples of supernatant collected at 12, 24, 36, 48, 60, and 72 h were detected. The results showed that the rapid growth period of the virus load of all the 3 generations was approximately 12-36 h post-infection; the peak of the virus load appeared at 36 h post-infection and then decreased gradually in the order of 20th > 54th > 87th for the 3 generations of CEK-adapted strains; the dynamic change curve of the IBV load in the supernatant of primary CEK cells showed a single peak. The results of this study provide a useful reference for CEK-adapted IBV field strains and the production of CEK-attenuated IBV vaccine.
Assuntos
Infecções por Coronaviridae/imunologia , Vírus da Bronquite Infecciosa/imunologia , Doenças das Aves Domésticas/imunologia , Vacinas Atenuadas/imunologia , Vacinas Virais/imunologia , Animais , Embrião de Galinha/imunologia , Embrião de Galinha/virologia , Infecções por Coronaviridae/prevenção & controle , Infecções por Coronaviridae/virologia , Vírus da Bronquite Infecciosa/patogenicidade , Rim/imunologia , Rim/virologia , Doenças das Aves Domésticas/prevenção & controle , Doenças das Aves Domésticas/virologia , Cultura Primária de Células , Vacinas Atenuadas/uso terapêutico , Carga Viral/imunologia , Vacinas Virais/uso terapêuticoRESUMO
The rates of radial oxygen loss (ROL), root porosity, concentrations of arsenic (As), iron (Fe) and manganese (Mn) in shoot and root tissues and on root surfaces, As tolerances, and their relationships in different wetland plants were investigated based on a hydroponic experiment (control, 0.8, 1.6 mg As L(-1)) and a soil pot trail (control, 60 mg As kg(-1)). The results revealed that wetland plants showed great differences in root porosity (9-64%), rates of ROL (55-1750 mmo1 O2 kg(-1) root d.w.d(-1)), As uptake (e.g., 8.8-151 mg kg(-1) in shoots in 0.8 mg As L(-1) treatment), translocation factor (2.1-47% in 0.8 mg As L(-1)) and tolerance (29-106% in 0.8 mg As L(-1)). Wetland plants with higher rates of ROL and root porosity tended to form more Fe/Mn plaque, possess higher As tolerance, higher concentrations of As on root surfaces and a lower As translocation factor so decreasing As toxicity.
Assuntos
Arsênio/metabolismo , Oxigênio/metabolismo , Raízes de Plantas/metabolismo , Áreas Alagadas , Ferro/metabolismo , Manganês/metabolismoRESUMO
The influence of salicylic acid on the production of taxanes in plant cell culture was studied. Experimental results showed that addition of salicylic acid at concentration of 0.1 mg/L could enhance the production of taxol to three-fold. The concentration of 10-DAB and baccatin III was also increasing while taxol concentration increases under salicylic acid elicitation. On the basis of the kinetic analysis about the simplified taxol biosynthesis pathway, a probable reason that salicylic acid improves the rate of 10-DAB producing reaction was introduced. The results above can direct its inducing mechanic research and provide the basis of multiple-elicitors synergism. The concentration of taxol arrives at 39 mg.L-1 induced by salicylic acid with silver nitrate, being 150 percent of the sum of taxol obtained under elicitation of salicylic acid and silver nitrate respectively.
Assuntos
Antineoplásicos Fitogênicos/biossíntese , Paclitaxel/biossíntese , Ácido Salicílico/farmacologia , Nitrato de Prata/farmacologiaRESUMO
The discovery of the reversible antifertility action of an extract from Tripterygium wilfordii both in male rats and in men in 1986 stimulated worldwide interest. International and national collaborations aimed at the bioassay-directed sub-fractionation of materials extracted from the plant was then organized and to date, a series of six male antifertility diterpene epoxides have been isolated. Their chemical structures have been identified and found to be triptolide, tripdiolide, triptolidenol, tripchlorolide, 16-hydroxytriptolide and T7/19 (structure not yet published). At the ED95 dosage levels, they act mainly on metamorphosing spermatids and testicular and epdidymal spermatozoa with exfoliation and inhibition of basic nuclear protein turnover of late spermatids, delayed spermiation and sperm head-tail separation and microtubule, microfilament and membrane damages. A preliminary toxic evaluation indicated that these compounds were immunosuppressive at dose levels 5-12 times their antifertility doses. Immuno-suppression is an important weakness for an antifertility agent, but if the immuno-suppressive dose of a drug is much higher than its antifertility dose, it could yet be regarded as a safe contraceptive. Therefore, in the safety evaluation of compounds isolated from Tripterygium wilfordii, it warrants our attention to probe deeply into their precise dose/immuno-effect relationship.