RESUMO
Objective: To analyze the course of disease and epidemiological parameters of COVID-19 and provide evidence for making prevention and control strategies. Methods: To display the distribution of course of disease of the infectors who had close contacts with COVID-19 cases from January 1 to March 15, 2020 in Guangdong Provincial, the models of Lognormal, Weibull and gamma distribution were applied. A descriptive analysis was conducted on the basic characteristics and epidemiological parameters of course of disease. Results: In total, 515 of 11 580 close contacts were infected, with an attack rate about 4.4%, including 449 confirmed cases and 66 asymptomatic cases. Lognormal distribution was fitting best for latent period, incubation period, pre-symptomatic infection period of confirmed cases and infection period of asymptomatic cases; Gamma distribution was fitting best for infectious period and clinical symptom period of confirmed cases; Weibull distribution was fitting best for latent period of asymptomatic cases. The latent period, incubation period, pre-symptomatic infection period, infectious period and clinical symptoms period of confirmed cases were 4.50 (95%CI:3.86-5.13) days, 5.12 (95%CI:4.63-5.62) days, 0.87 (95%CI:0.67-1.07) days, 11.89 (95%CI:9.81-13.98) days and 22.00 (95%CI:21.24-22.77) days, respectively. The latent period and infectious period of asymptomatic cases were 8.88 (95%CI:6.89-10.86) days and 6.18 (95%CI:1.89-10.47) days, respectively. Conclusion: The estimated course of COVID-19 and related epidemiological parameters are similar to the existing data.
Assuntos
COVID-19 , Busca de Comunicante , Estudos de Coortes , Humanos , Incidência , Estudos ProspectivosRESUMO
The androgen receptor (AR) is involved in the differentiation and growth of breast cancer. Genetic markers in the AR gene have a plausible role in modulating the risk of breast cancer. In this study, we studied the association of breast cancer and the trinucleotide repeat polymorphism (CAG)n in exon 1 of the AR gene in 202 patients with breast cancer and 183 healthy controls from our hospital (Yinchuan, China). Repeat lengths were determined by fluorescent DNA fragment analysis using the ABI GeneScan software and DNA sequencing. We detected 17 short tandem repeat alleles in exon 1 in the Han population of Ningxia Province, China. The CAG repeat number ranged from 14 to 31 and the frequency ranged from 0.339 to 24.460%. Generally, (CAG)n repeat lengths <22 were classified as short (S), and those >22 were classified as long (L). No association was found between breast cancer and the S/L (CAG) variants. However, the frequency of the (CAG)25 repeats in the breast cancer group was significantly higher than that in the control group (P = 0.033, odds ratio = 1.790, 95% confidence interval = 1.044-3.069). These findings indicate a role for AR gene (CAG)n variations in breast cancer and might be informative for future genetic or biological studies on breast cancer, although these findings need replication in other populations.
Assuntos
Povo Asiático/genética , Neoplasias da Mama/genética , Etnicidade/genética , Predisposição Genética para Doença , Receptores Androgênicos/genética , Repetições de Trinucleotídeos/genética , Sequência de Bases , Estudos de Casos e Controles , Feminino , Frequência do Gene/genética , Humanos , Pessoa de Meia-Idade , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Fatores de Risco , Análise de Sequência de DNARESUMO
Previous studies suggested that dopamine receptors may be associated with drug dependence and impulsive behavior. In this study, we examined whether dopamine receptor D1 (DRD1) is associated with heroin dependence and the impulsive behavior in patients with heroin dependence. The participants included 367 patients with heroin dependence and 372 healthy controls from a Chinese Han population. We examined the potential association between heroin dependence and 8 single-nucleotide polymorphisms (rs686, rs4867798, rs1799914, rs4532, rs5326, rs265981, rs10078714, rs10078866) of DRD1, and the associations between single single-nucleotide polymorphism, haplotypes, and impulsive behavior. Compared with the healthy controls, heroin dependence patients showed a significantly lower frequency of GG homozygotes of rs5326 (P = 0.027), significantly lower frequency of the G allele of rs5326 (P = 0.007, odds ratio = 0.718, 95% confidence interval = 0.565-0.913), and higher frequency of the rs265981 G allele (P = 0.0002, odds ratio = 1.711, 95% confidence interval = 1.281-2.287). Furthermore, strong linkage disequilibrium was observed in 2 blocks (D' > 0.9). However, no association was observed between haplotypes and heroin dependence in the 2 blocks. This genetic behavior correlation study showed that the 2 single-nucleotide polymorphisms, rs5326 and rs265981, were not associated with the impulsive behavior in patients with heroin dependence. These findings indicate that DRD1 gene polymorphisms are related to heroin dependence in a Chinese Han population and may be informative for future genetic or biological studies on heroin dependence.
Assuntos
Dependência de Heroína/genética , Polimorfismo de Nucleotídeo Único , Receptores de Dopamina D1/genética , Adulto , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , Estudos de Associação Genética , Genótipo , Haplótipos , Humanos , Comportamento Impulsivo , Desequilíbrio de Ligação , Pessoa de Meia-Idade , Razão de ChancesRESUMO
Heroin dependence is a debilitating psychiatric disorder with a complex inheritance mechanism. Genetic polymorphisms in functional regions of the glutamate receptor, N-methyl D-aspartate 2A (GRIN2A) gene, which encodes the 2A subunit of the N-methyl D-aspartate (NMDA) receptor, may modulate the risk of heroin addiction. We investigated the potential association between 8 single nucleotide polymorphisms (SNPs) of the GRIN2A gene (SNPs rs3219790, rs1014531, rs8044472, rs8045712, rs9933624, rs9940680, rs1420040, and rs767749) and heroin addiction using the MassARRAY system and GeneScan. A total of 405 heroin-addicted patients and 397 healthy control subjects were recruited for this study. Statistically significant differences were observed for rs3219790 in the promoter region of the GRIN2A gene. The frequency of the (GT)26 repeats in the heroin addiction group was significantly higher than that in the control group [X(2) = 5.475, P = 0.019, odds ratio (OR) = 1.367, 95% confidence interval (CI) = 1.051-1.776]. Strong linkage disequilibrium was observed in block 1 (D' > 0.9). However, significant evidence of linkage disequilibrium was not observed between the 7 SNPs in our sample population. These data suggest that GRIN2A gene polymorphisms confer susceptibility to heroin addiction and support the hypothesis that dysfunction of GRIN2A is involved in the pathophysiological process of heroin addiction.
Assuntos
Dependência de Heroína/genética , Polimorfismo de Nucleotídeo Único , Receptores de N-Metil-D-Aspartato/genética , Adulto , Estudos de Casos e Controles , Humanos , Desequilíbrio de Ligação , Regiões Promotoras GenéticasRESUMO
Epithelial ovarian cancer (EOC) is the leading cause of death among all gynecological cancers. Nuclear factor-kappa B (NF-κB) is involved in carcinogenesis and in the development of EOC. The ß-transducin repeat-containing protein (ß-TrCP) is a positive regulator of the NF-κB signaling pathway. Recent studies have indicated that the -94 ins/del ATTG polymorphism in the promoter region of the NFKB1 gene, and the 9N ins/del polymorphism in the 3'-untranslated region of the ß-TrCP gene are associated with increased susceptibility to a variety of cancers. We examined a potential association between these two polymorphisms and EOC. Genotypes were determined for 187 patients with EOC and 221 healthy control subjects, using the MassARRAY system. We found a significant association between the -94 ins/del ATTG genotype distribution and EOC. The frequency of the -94 del ATTG allele was significantly lower in EOC patients compared to healthy controls. The NF-κB mRNA level in cancer tissue was significantly correlated with -94 ins/del ATTG genotypes. Compared to the ATTG1/ATTG1 phenotype, the NF-κB mRNA level was 2.089 and 1.257 times higher in the ATTG2 (insertion)/ATTG2 homozygote and the ATTG1 (deletion)/ATTG2 heterozygote, respectively. However, we found no evidence of association between the 9N ins/del polymorphism of the ß-TrCP gene and EOC in this Chinese population. Based on these results, we suggest that the NF-κB -94 ins/del ATTG polymorphism is a risk factor for EOC susceptibility.
Assuntos
Estudos de Associação Genética , Subunidade p50 de NF-kappa B/genética , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Ovarianas/genética , Proteínas Contendo Repetições de beta-Transducina/genética , Adulto , Idoso , Povo Asiático , Carcinoma Epitelial do Ovário , Feminino , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Humanos , Mutação INDEL , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Regiões Promotoras Genéticas , RNA Mensageiro/genéticaRESUMO
Methionine is indispensable for growth and meat formation in pigs. However, it is still unclear that increasing dietary sulphur-containing amino acid (SAA) levels using different methionine sources affects the growth performance and meat quality of barrows and gilts. To investigate this, 144 pigs (half barrows and half gilts) were fed the control (100% SAA, CON), DL-Methionine (125% SAA, DL-Met)-supplemented, or OH-Methionine (125% SAA, OH-Met)-supplemented diets during the 11-110 kg period. The results showed that plasma methionine levels varied among treatments during the experimental phase, with increased plasma methionine levels observed following increased SAA consumption during the 25-45 kg period. In contrast, pigs fed the DL-Met diet had lower plasma methionine levels than those fed the CON diet (95-110 kg). Additionally, gilts fed the DL-Met or OH-Met diets showed decreased drip loss in longissimus lumborum muscle (LM) compared to CON-fed gilts. OH-Met-fed gilts had higher pH45min values than those fed the CON or DL-Met diets, whereas OH-Met-fed barrows had higher L45min values than those fed the CON or DL-Met diets. Moreover, increased consumption of SAA, regardless of the methionine source, tended to decrease the shear force of the LM in pigs. In conclusion, this study indicates that increasing dietary levels of SAA (+25%) appeared to improve the meat quality of gilts by decreasing drip loss and increasing meat tenderness.
Assuntos
Suplementos Nutricionais , Metionina , Suínos , Animais , Feminino , Metionina/farmacologia , Dieta/veterinária , Carne , Sus scrofa , Racemetionina/farmacologia , Ração Animal/análise , Composição CorporalRESUMO
BACKGROUND: We used recombinant adeno-associated virus vector of adiponectin (AAV2/1-Acrp30) to study the effects of increased levels of adioponectin (by the administration of rAAV2/1-Acrp30) on arteriosclerosis, glucose and lipid metabolism in Goto-Kakizaki (GK) rats with arteriosclerosis. METHODS: Thirty GK rats with arteriosclerosis were divided into 3 equal groups: control group 1, control group 2 and the rAAV2/1-Acrp30-administered group. Saline, virus vector or rAAV2/1-Acrp30 (10 12 ng/ml) vector genomes administered to the rats in the corresponding group by intramuscular injection to the posterior limb by single administration, respectively. After 8 weeks, fasting blood glucose, 2-hour postprandial blood glucose, glycosylated haemoglobin, serum insulin, serum total cholesterol, triglycerides, high-density lipoprotein and low-density lipoprotein were measured in each group, and the ultrastructure of the aorta was seen by light and electron microscopy. RESULTS: Compared with control groups 1 and 2, in the rAAV2/1-Acrp30 group, there was a decrease in urine volume, fasting blood glucose, 2-hour postprandial blood glucose, glycosylated haemoglobin, serum total cholesterol, triglycerides and low-density lipoprotein, and an increase in body weight and high-density lipoprotein (p< 0.05), while the level of serum insulin was not changed (p>0.05). Ultrastructure studies of the aorta showed that aortosclerosis in the rAAV2/1-Acrp30-administered group was less, and fewer lipid droplet vacuoles were seen in the vascular endothelial cytoplasm. Also various cell organelles and internal elastic lamina were seen, and there was no formation of lipid droplet and foam cells in the cytoplasm of the media of the smooth muscle. CONCLUSION: Adiponectin could improve blood glucose and lipid parameters and decrease atherosclerosis in the aorta of GK rats.
Assuntos
Adenoviridae/genética , Adiponectina/genética , Doenças da Aorta , Arteriosclerose , Terapia Genética/métodos , Animais , Aorta/patologia , Aorta/ultraestrutura , Doenças da Aorta/metabolismo , Doenças da Aorta/patologia , Doenças da Aorta/terapia , Arteriosclerose/metabolismo , Arteriosclerose/patologia , Arteriosclerose/terapia , Glicemia/metabolismo , Metabolismo dos Lipídeos/genética , Masculino , Ratos , Ratos Endogâmicos , Proteínas Recombinantes/genéticaRESUMO
The COVID-19 pandemic is still ongoing in the world, the risk of COVID-19 spread from other countries or in the country will exist for a long term in China. In the routine prevention and control phase, a number of local COVID-19 epidemics have occurred in China, most COVID-19 cases were sporadic ones, but a few case clusters or outbreaks were reported. Winter and spring were the seasons with high incidences of the epidemics; border and port cities had higher risk for outbreaks. Active surveillance in key populations was an effective way for the early detection of the epidemics. Through a series of comprehensive prevention and control measures, including mass nucleic acid screening, close contact tracing and isolation, classified management of areas and groups at risk, wider social distancing and strict travel management, the local COVID-19 epidemics have been quickly and effectively controlled. The experiences obtained in the control of the local epidemics would benefit the routine prevention and control of COVID-19 in China. The occurrence of a series of COVID-19 case clusters or outbreaks has revealed the weakness or deficiencies in the COVID-19 prevention and control in China, so this paper suggests some measures for the improvement of the future prevention and control of COVID-19.
Assuntos
COVID-19 , Epidemias , COVID-19/epidemiologia , COVID-19/prevenção & controle , China/epidemiologia , Busca de Comunicante , Epidemias/prevenção & controle , Humanos , Pandemias/prevenção & controle , SARS-CoV-2RESUMO
BACKGROUND: : Glucocorticoids are the central effector hormones for the hypothalamic-pituitary-adrenal axis. However, the effects of endogenous glucocorticoids on the immune system are not understood completely. METHODS: : Macrophage function (adherence, chemotaxis and cytokine production) was assessed in the presence of increasing concentrations of corticosterone. The role of endoplasmic reticulum (ER) stress in corticosterone immunoregulation was determined with thapsigargin and plasmid pGCL-GFP-siXBP1. Mifepristone was used to determine the role of glucocorticoid receptor in the corticosterone-induced ER stress response. RESULTS: : Corticosterone exerted immunostimulatory effects on macrophage function at low concentrations. No effects were observed at high concentrations in the absence of immunological stimulation. Low-dose corticosterone induced ER stress, which was correlated to the corticosterone immunostimulatory activities. Expression of X box-binding protein (XBP) 1, but not activating transcription factor 6, was significantly increased at both mRNA and protein levels only in the presence of low-dose corticosterone. Inhibition of XBP1 expression with small interfering RNA significantly inhibited the corticosterone immunostimulatory effects. In addition, pretreatment of macrophages with mifepristone significantly inhibited the expression of glucose response protein 78 and XBP1 in macrophages by low-dose corticosterone. CONCLUSION: : At low concentrations, endogenous glucocorticoids exert immunostimulatory actions on macrophages. The underlying mechanisms may be correlated to ER stress via the glucocorticoid receptor, in which XBP1 plays an important role.
Assuntos
Adjuvantes Imunológicos/farmacologia , Corticosterona/farmacologia , Retículo Endoplasmático/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Animais , Adesão Celular/efeitos dos fármacos , Quimiotaxia/efeitos dos fármacos , Citocinas/biossíntese , Proteínas de Ligação a DNA/fisiologia , Relação Dose-Resposta a Droga , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Mifepristona/farmacologia , Fagocitose/efeitos dos fármacos , Receptores de Glucocorticoides/fisiologia , Fatores de Transcrição de Fator Regulador X , Tapsigargina/farmacologia , Fatores de Transcrição/fisiologia , Proteína 1 de Ligação a X-BoxRESUMO
Objective: To analyze the epidemiological characteristics of the cases firstly reported as "asymptomatic infection of COVID-19" in Guangdong province. Methods: The follow-up observation method was used to continuously track and observe the cases firstly reported as "asymptomatic patients with COVID-19" in Guangdong province from January 14 to March 31, 2020. The epidemiological data of the cases were collected to analyze their epidemiological characteristics, outcome and influencing factors. Results: From January 14 to March 31, 2020, a total of 325 cases were firstly reported as "asymptomatic infections of COVID-19" in Guangdong province. The epidemic curve of asymptomatic infection cases was similar to that of confirmed cases, and it had two peaks. The first peak was from January 27 to February 5, and the second peak was from March 17 to March 26. Of the 325 cases, 184 (56.6%) were subsequently converted to confirmed cases. These cases were defined as incubation period asymptomatic infection cases. The age median of the cases was 40 years, and 93.5% (172/184) of the cases showed symptoms within 3 days after the first positive nucleic acid tests were conducted, and 141 (43.4%) of the 325 cases remained asymptomatic status until they were cured and discharged. They were inapparent infection cases, accounting for 8.6% (141/1 642) of those diagnosed with COVID-19 in Guangdong province during the same period. The age median of inapparent infection cases was 27 years. The median of the interval between the first positive nucleic acid test and discharge was 14 days. Up to 90.8% (138/141) of the inapparent infection cases were discharged for centralized medical observation within 28 days. The longest interval between the first positive nucleic acid test and the last positive nucleic acid test was 73 days. The positive rate of nucleic acid test was 0.3% in close contacts of inapparent infection cases and 2.2% in close contacts of incubation period asymptomatic infection cases. There were significant differences in age distribution and source of infection between incubation period asymptomatic infection cases and inapparent infection cases (P<0.05). Old age was the risk factor for the conversion of firstly reported asymptomatic infection cases to confirmed cases. Compared with the 0-19-year-old group, The patients aged 40-59 years and 60 years and above were more likely to become confirmed cases. The OR (95%CI) values were 2.730 (1.380-5.402) and 5.302 (2.199-12.783), and P values were 0.004 and 0.000, respectively. People being infected in China were more likely to become confirmed cases (OR=7.121, P=0.000). Conclusions: There were asymptomatic infection cases among patients diagnosed with COVID-19. The infectiousness of incubation period asymptomatic infection cases might be stronger than that of inapparent infection cases. The proportion of younger cases among asymptomatic infection cases was higher than that of the confirmed cases. Old age and domestic infection were the risk factors for the conversion of asymptomatic infection cases to confirmed cases, to which more attention should be paid. Further serological investigations are needed to provide a basis for the development of COVID-19 prevention and control strategies.
Assuntos
Infecções Assintomáticas/epidemiologia , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Adolescente , Adulto , COVID-19 , Criança , Pré-Escolar , China/epidemiologia , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Pandemias , Adulto JovemRESUMO
Objective: To analyze the clinical courses and outcomes of COVID-19 cases and the influencing factors in Guangdong province and provide basis for the formulation or adjustment of medical care and epidemic control strategy for COVID-19. Methods: We collected demographic data, medical histories, clinical courses and outcomes of 1 350 COVID-19 patients reported in Guangdong as of 4 March 2020 via epidemiological investigation and process tracking. Disease severity and clinical course characteristics of the patients and influencing factors of severe illness were analyzed in our study. Results: Among 1 350 cases of COVID-19 cases in Guangdong, 72 (5.3%) and 1 049 (77.7%) were mild and ordinary cases, 164 (12.1%) were severe cases, 58 (4.3%) were critical cases and 7 (0.5%) were fatal. The median duration of illness were 23 days (P(25), P(75): 18, 31 days) and the median length of hospitalization were 20 days (P(25), P(75): 15,27 days). For severe cases, the median time of showing severe manifestations was on the 12(th) day after onset (P(25), P(75): 9(th) to 15(th) days), and the median time of severe manifestation lasted for 8 days (P(25), P(75): 4, 14 days). Among 1 066 discharged/fetal cases, 36.4% (36/99) and 1.0% (1/99) of the mild cases developed to ordinary cases and severe cases respectively after admission; and 5.2% (50/968) and 0.6% (6/968) of the ordinary cases developed to severe cases, and critical cases respectively after admission. In severe cases, 11.4% developed to critical cases (10/88). The influencing factors for severe illness or worse included male (aHR=1.87, 95%CI: 1.43-2.46), older age (aHR=1.67, 95%CI: 1.51-1.85), seeking medical care on day 2-3 after onset (aHR=1.73, 95%CI: 1.20-2.50) pre-existing diabetes (aHR=1.75, 95%CI: 1.12-2.73) and hypertension (aHR=1.49, 95%CI: 1.06-2.09). Conclusions: The course of illness and length of hospitalization of COVID-19 cases were generally long and associated with severity of disease clinical outcomes. The severe cases were mainly occurred in populations at high risk. In the epidemic period, classified management of COVID-19 cases should be promoted according to needs for control and prevention of isolation and treatment for the purpose of rational allocation of medical resources.
Assuntos
COVID-19 , Idoso , COVID-19/epidemiologia , China/epidemiologia , Hospitalização , Humanos , Masculino , Alta do Paciente , SARS-CoV-2RESUMO
Objective: To assess the imported risk of COVID-19 in Guangdong province and its cities, and conduct early warning. Methods: Data of reported COVID-19 cases and Baidu Migration Index of 21 cities in Guangdong province and other provinces of China as of February 25, 2020 were collected. The imported risk index of each city in Guangdong province were calculated, and then correlation analysis was performed between reported cases and the imported risk index to identify lag time. Finally, we classified the early warming levels of epidemic by imported risk index. Results: A total of 1 347 confirmed cases were reported in Guangdong province, and 90.0% of the cases were clustered in the Pearl River Delta region. The average daily imported risk index of Guangdong was 44.03. Among the imported risk sources of each city, the highest risk of almost all cities came from Hubei province, except for Zhanjiang from Hainan province. In addition, the neighboring provinces of Guangdong province also had a greater impact. The correlation between the imported risk index with a lag of 4 days and the daily reported cases was the strongest (correlation coefficient: 0.73). The early warning base on cumulative 4-day risk of each city showed that Dongguan, Shenzhen, Zhongshan, Guangzhou, Foshan and Huizhou have high imported risks in the next 4 days, with imported risk indexes of 38.85, 21.59, 11.67, 11.25, 6.19 and 5.92, and the highest risk still comes from Hubei province. Conclusions: Cities with a large number of migrants in Guangdong province have a higher risk of import. Hubei province and neighboring provinces in Guangdong province are the main source of the imported risk. Each city must strengthen the health management of migrants in high-risk provinces and reduce the imported risk of Guangdong province.
Assuntos
Doenças Transmissíveis Importadas , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , COVID-19 , China/epidemiologia , Cidades , Monitoramento Epidemiológico , Humanos , Pandemias , Medição de RiscoRESUMO
Objective: To validate the prognostic value of NCCN-International Prognostic Index (NCCN-IPI) for patients with peripheral T-cell lymphoma (PTCL) treated with CHOP-based chemotherapy. Methods: A retrospective analysis in 162 PTCL patients who were initially diagnosed and treated in Rui Jin Hospital from January 2003 to May 2013 was conducted. Baseline characteristics were collected, and survival analysis was performed according to the IPI and NCCN-IPI model. Results: The estimated 5-year overall survival (OS) rate and progression free survival (PFS) rate were 33% and 20%, with median OS and PFS of 17.0 months and 9.2 months, respectively. Multivariate analysis indicated ECOG score (PFS: HR=2.418, 95%CI 1.535-3.809, P<0.001; OS: HR=2.347, 95%CI 1.435-3.839, P= 0.001) , specific extra-nodal sites (PFS: HR=1.800, 95%CI 1.216-2.665, P=0.003; OS: HR=1.608, 95% CI 1.054-2.454, P=0.027) and pathology type (PFS: HR=0.424, 95% CI 0.184-0.975, P=0.043; OS: HR=0.276, 95% CI 0.087-0.877, P=0.029) were independent prognostic factors of OS and PFS for the patients with PTCL. The survival rates of low risk patients based on NCCI-IPI were remarkably higher than the counterparts based on IPI (5-year OS 74% vs 54%, χ(2)=5.041, P=0.025, 5-year PFS 50% vs 38%, χ(2)= 5.295, P=0.021) . NCCN-IPI was outstanding to identify the subgroup of low risk patients with PTCL, who may benefit from conventional chemotherapy such as CHOP or CHOP-like regimen. Conclusion: NCCN-IPI is more powerful for low risk PTCL patients and a strong supplement for IPI.
Assuntos
Linfoma de Células T Periférico , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Linfoma Difuso de Grandes Células B , Prognóstico , Estudos RetrospectivosRESUMO
Objective: To analyze the efficacy of additional two cycles of rituximab administration for Chinese patients with diffuse large B-cell lymphoma (DLBCL) in first complete remission (CR) after six cycles of standard 21-day rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP21). Methods: Retrospective analysis was performed in 351 patients with DLBCL diagnosed from March 2003 to March 2012. International Prognosis Index (IPI), Revised (R)-IPI and National Comprehensive Cancer Network (NCCN)-IPI were calculated for each patient. Patients were divided into GCB and non-GCB subtype according to Han's Classification. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier methods. Results: 282 (80.3%) patients achieved CR and 132 (46.8%) of 282 cases received additional two rituximab therapy. The other 150 (53.2%) patients entered into observation on the intention of the patients. No significant difference was observed in baseline characteristics between the two groups. 3-year estimated PFS for additional rituximab group and observation group were 80.0% and 78.1% (P=0.334), while 3-year estimated OS were 89.7% vs. 86.1% (P=0.452). By subgroup analysis, prolonged PFS were observed in R-IPI low-risk and NCCN-IPI low-risk patients after additional two rituximab cycles. Conclusion: For patients with DLBCL in first remission after standard six cycles of R-CHOP21 regimen, additional two cycles of rituximab maintenance did not significantly improve the general prognosis, but low-risk subgroups of R-IPI and NCCN-IPI could benefit from this regimen.
Assuntos
Anticorpos Monoclonais Murinos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Rituximab/uso terapêutico , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina , Humanos , Prednisona/administração & dosagem , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Vincristina/administração & dosagemRESUMO
A clinical trial was conducted in order to evaluate the therapeutic effect and side-effects of low-dose ATRA in the treatment of acute promyelocytic leukemia (APL). We compared the pharmacokinetic features in normal individuals with single oral ATRA at 15 mg/m2 and 45 mg/m2, respectively. The results showed that maximal plasma concentration (Cpmax) with oral 15 mg/m2 ATRA was high enough (10(-6) M) to induce APL cell differentiation. Based on these results, 27 cases of de novo APL patients were treated with continuous oral ATRA at the dose of 15-20 mg/m2/day and 24/26 evaluable cases (92%) achieved clinical CR after 13 to 67 days of ATRA treatment. No patient experienced RAS and DIC. The Cpmax with a single dose of ATRA on day 1 of treatment and immediately at CR obtained with continuous ATRA in three cases demonstrated similar values in one patient and an approximately two-fold decrease in two patients. More importantly, compared with a relatively well-matched historic group of 20 APL patients treated with high-dose ATRA, our results suggest that low-dose ATRA is as effective as high-dose in treating APL patients and may provide advantages through decreased hyperleukocytosis and other side-effects.
Assuntos
Fatores Imunológicos/farmacocinética , Leucemia Promielocítica Aguda/terapia , Tretinoína/farmacocinética , Administração Oral , Adulto , Feminino , Meia-Vida , Humanos , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Leucemia Promielocítica Aguda/mortalidade , Leucocitose/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Tretinoína/administração & dosagem , Tretinoína/efeitos adversos , Tretinoína/uso terapêuticoRESUMO
This report firstly describes the pharmacokinetic study of liposomal breviscapine (LB) after oral administration in rats. The mean Cmax and AUC(0-->t) of LB were 3.3 and 3.1-fold higher than those of breviscapine solution (BS). The oral absorption of breviscapine was significantly increased after encapsulation in the liposomal formulation.
Assuntos
Anticoagulantes/farmacocinética , Flavonoides/farmacocinética , Animais , Anticoagulantes/administração & dosagem , Área Sob a Curva , Disponibilidade Biológica , Química Farmacêutica , Cromatografia Líquida de Alta Pressão , Portadores de Fármacos , Composição de Medicamentos , Feminino , Flavonoides/administração & dosagem , Lipossomos , Masculino , Ratos , Ratos Wistar , Reprodutibilidade dos Testes , Espectrofotometria UltravioletaRESUMO
Small unilamellar liposomes (SUV) of different phospholipid/polymer composition were labeled with NBD-PC, which served as a bilayersituated fluorescence marker. Neonatal cardiomyocytes were incubated with liposomes and then the cell-associated fluorescence was measured. The factors influencing the liposome uptake by cardiomyocytes such as concentration of lipid, time of incubation, membrane fluidity of liposomes, charge lipid/polymer modification of liposomes and anoxia of cultured cardiomyocytes were investigated. The liposome uptake by cardiomyocytes increased dose-dependently and time-dependently. Liposome uptake was strongly influenced by the electrical charge and modified polymer. After 2 h incubation, the uptake of positively charged liposomes was 1.7-fold higher than that of negatively charged one and both higher than that of the neutral one. The presence of PE-PEG2000 distinctly reduced the liposome uptake and the difference between the uptake of charged and neutral liposome. Anoxia increased the uptake of liposome at the first hour (increased 20%), but after 2 h incubation the liposome uptake by hypoxia cellswas less than that of normoxia cells (decreased 18%). Mechanisms involved are also discussed.
Assuntos
Lipossomos/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Hipóxia Celular , Células Cultivadas , Eletroquímica , Lipídeos/química , Lipossomos/química , Fluidez de Membrana , Fosfolipídeos , Polietilenoglicóis , RatosRESUMO
Background. We used recombinant adeno-associated virus vector of adiponectin (AAV2/1-Acrp30) to study the effects of increased levels of adioponectin (by the administration of rAAV2/1-Acrp30) on arteriosclerosis, glucose and lipid metabolism in Goto–Kakizaki (GK) rats with arteriosclerosis. Methods. Thirty GK rats with arteriosclerosis were divided into 3 equal groups: control group 1, control group 2 and the rAAV2/1-Acrp30-administered group. Saline, virus vector or rAAV2/1-Acrp30 (1012 ng/ml) vector genomes administered to the rats in the corresponding group by intramuscular injection to the posterior limb by single administration, respectively. After 8 weeks, fasting blood glucose, 2-hour postprandial blood glucose, glycosylated haemoglobin, serum insulin, serum total cholesterol, triglycerides, high-density lipoprotein and low-density lipoprotein were measured in each group, and the ultrastructure of the aorta was seen by light and electron microscopy. Results. Compared with control groups 1 and 2, in the rAAV2/1-Acrp30 group, there was a decrease in urine volume, fasting blood glucose, 2-hour postprandial blood glucose, glycosylated haemoglobin, serum total cholesterol, triglycerides and low-density lipoprotein, and an increase in body weight and high-density lipoprotein (p<0.05), while the level of serum insulin was not changed (p>0.05). Ultrastructure studies of the aorta showed that aortosclerosis in the rAAV2/1-Acrp30-administered group was less, and fewer lipid droplet vacuoles were seen in the vascular endothelial cytoplasm. Also various cell organelles and internal elastic lamina were seen, and there was no formation of lipid droplet and foam cells in the cytoplasm of the media of the smooth muscle. Conclusion. Adiponectin could improve blood glucose and lipid parameters and decrease atherosclerosis in the aorta of GK rats.