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Erythropoiesis is a complex multistage process that involves differentiation of early erythroid progenitors to enucleated mature red blood cells, in which lineage-specific transcription factors play essential roles. Erythroid Krüppel-like factor (EKLF/KLF1) is a pleiotropic erythroid transcription factor that is required for the proper maturation of the erythroid cells, whose expression and activation are tightly controlled in a temporal and differentiation stage-specific manner. Here, we uncover a novel role of G-protein pathway suppressor 2 (GPS2), a subunit of the nuclear receptor corepressor/silencing mediator of retinoic acid and thyroid hormone receptor corepressor complex, in erythrocyte differentiation. Our study demonstrates that knockdown of GPS2 significantly suppresses erythroid differentiation of human CD34+ cells cultured in vitro and xenotransplanted in nonobese diabetic/severe combined immunodeficiency/interleukin-2 receptor γ-chain null mice. Moreover, global deletion of GPS2 in mice causes impaired erythropoiesis in the fetal liver and leads to severe anemia. Flow cytometric analysis and Wright-Giemsa staining show a defective differentiation at late stages of erythropoiesis in Gps2-/- embryos. Mechanistically, GPS2 interacts with EKLF and prevents proteasome-mediated degradation of EKLF, thereby increasing EKLF stability and transcriptional activity. Moreover, we identify the amino acids 191-230 region in EKLF protein, responsible for GPS2 binding, that is highly conserved in mammals and essential for EKLF protein stability. Collectively, our study uncovers a previously unknown role of GPS2 as a posttranslational regulator that enhances the stability of EKLF protein and thereby promotes erythroid differentiation.
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Eritropoese/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Fatores de Transcrição Kruppel-Like/fisiologia , Sequência de Aminoácidos , Animais , Células Cultivadas , Sequência Conservada , Células Precursoras Eritroides/citologia , Técnicas de Silenciamento de Genes , Transplante de Células-Tronco Hematopoéticas , Humanos , Subunidade gama Comum de Receptores de Interleucina/deficiência , Peptídeos e Proteínas de Sinalização Intracelular/biossíntese , Peptídeos e Proteínas de Sinalização Intracelular/deficiência , Peptídeos e Proteínas de Sinalização Intracelular/genética , Fatores de Transcrição Kruppel-Like/antagonistas & inibidores , Fatores de Transcrição Kruppel-Like/química , Fígado/embriologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos SCID , Mapeamento de Interação de Proteínas , Processamento de Proteína Pós-Traducional , Estabilidade Proteica , Proteólise , Interferência de RNA , RNA Interferente Pequeno/genética , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Transcrição Gênica , Transplante Heterólogo , Ubiquitinação , Regulação para CimaRESUMO
The nucleotide-binding domain and leucine-rich repeat-containing family pyrin domain containing 3 (NLRP3) inflammasome is involved in various acute and chronic liver diseases, however, it is not clear whether NLRP3 contributes to d-Galactosamine (D-GalN) plus lipopolysaccharide (LPS)-induced acute liver failure (ALF). This study aims to investigate the role of NLRP3 inflammasome in D-GalN/LPS-induced fatal hepatitis. We found that Nlrp3-/- and WT mice showed similar mortality against a lethal dose of D-GalN/LPS treatment. Serum ALT and AST levels, as well as liver necrosis area and hepatocyte apoptosis, were not significantly different between Nlrp3-/- and WT mice at 6 h after D-GalN/LPS injection. Moreover, the numbers of intrahepatic F4/80+ cells and Ly6G+ cells were comparable in two genotype mice following D-GalN/LPS treatment. Besides, Nlrp3-/- mice had reduced IL-1ß levels but similar TNF-α, IL-6, and MCP-1 levels compared with WT mice upon D-GalN/LPS administration. Our findings revealed that NLRP3 ablation does not protect mice from D-GalN/LPS-induced fatal hepatitis and has a marginal effect on intrahepatic inflammatory response upon D-GalN/LPS treatment. This suggests that NLRP3 inflammasome does not appear to be a major contributor to D-GalN/LPS-induced ALF.
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Falência Hepática Aguda/etiologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/fisiologia , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Galactosamina , Inflamassomos/metabolismo , Inflamassomos/fisiologia , Interleucina-1beta/sangue , Lipopolissacarídeos , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/imunologia , Falência Hepática Aguda/metabolismo , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fator de Necrose Tumoral alfa/sangueRESUMO
A nickel-catalyzed decarbonylation or decarbonylation accompanied by decarboxylation cross-coupling reaction of aryl anhydrides with thiophenols as coupling partners was disclosed. This method is promoted by a commercially available, moisture-stable, and inexpensive nickel(II) precatalyst. The process can tolerate a variety of functional groups using ubiquitous aryl anhydrides as cross-coupling precursors to produce thioethers in moderate to excellent yields.
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Efficient one-pot synthesis of N-imidoyl-(1 H)-indoles has been described, which is achieved by the palladium-catalyzed oxidative insertion of 2-(phenylethynyl)aniline, arylboronic acid, and isonitrile. This method provides a new way to synthesize N-imidoyl-(1 H)-indoles, which has a wide substrate scope, good functional group tolerance, and mild reaction condition.
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A novel palladium-catalyzed oxidative three-component coupling of easily accessible N-substituted anthranilamides with isocyanides and arylboronic acids is achieved. This protocol offers an alternative approach toward 2,3-disubstituted quinazolinones with a wide substrate scope and good functional group tolerance.
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A Cu-mediated stereoselective [4+2] annulation between N-hydroxybenzimidoyl cyanides and norbornene (NBE) has been developed for the synthesis of 4 H-1,2-oxazin-4-ones. The reaction proceeds through sequentially forming C-O/C-C bonds. The advantage of this reaction includes high stereoselectivity, excellent yields, as well as simple and mild reaction conditions. A total of 26 examples are presented along with some control experiments.
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BRCA1/BRCA2-containing complex subunit 3 (BRCC3) is a lysine 63-specific deubiquitinase involved in multiple biological processes, such as DNA repair and immune responses. However, the regulation mechanism for BRCC3 protein stability is still unknown. Here, we demonstrate that BRCC3 is mainly degraded through the ubiquitin-proteasome pathway. The HECT-type E3 ubiquitin ligase WWP2 modulates BRCC3 ubiquitination and degradation. ABRO1, a subunit of the BRCC36 isopeptidase complex (BRISC), competes with WWP2 to bind to BRCC3, thereby preventing WWP2-mediated BRCC3 ubiquitination and enhancing BRCC3 stability. Functionally, we show that lentivirus-mediated overexpression of WWP2 in murine macrophages inhibits NLRP3 inflammasome activation by decreasing BRCC3 protein level. This study provides the first insights into the regulation of BRCC3 stability and expands our knowledge about the physiological function of WWP2.
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Enzimas Desubiquitinantes/química , Enzimas Desubiquitinantes/metabolismo , Proteínas Associadas à Matriz Nuclear/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Proteases Específicas de Ubiquitina/metabolismo , Animais , Linhagem Celular , Células Cultivadas , Enzimas Desubiquitinantes/genética , Técnicas de Inativação de Genes , Células HEK293 , Humanos , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos , Proteínas Associadas à Matriz Nuclear/genética , Estabilidade Proteica , Proteólise , Proteases Específicas de Ubiquitina/genética , UbiquitinaçãoRESUMO
Pharmacologically inhibiting nucleotide-binding domain and leucine-rich repeat-containing (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome activation results in potent therapeutic effects in a wide variety of preclinical inflammatory disease models. NLRP3 deubiquitination is essential for efficient NLRP3 inflammasome activity, but it remains unclear whether this process can be harnessed for therapeutic benefit. Here, we show that thiolutin (THL), an inhibitor of the JAB1/MPN/Mov34 (JAMM) domain-containing metalloprotease, blocks NLRP3 inflammasome activation by canonical, noncanonical, alternative, and transcription-independent pathways at nanomolar concentrations. In addition, THL potently inhibited the activation of multiple NLRP3 mutants linked with cryopyrin-associated periodic syndromes (CAPS). Treatment with THL alleviated NLRP3-related diseases in mouse models of lipopolysaccharide-induced sepsis, monosodium urate-induced peritonitis, experimental autoimmune encephalomyelitis, CAPS, and methionine-choline-deficient diet-induced nonalcoholic fatty liver disease. Mechanistic studies revealed that THL inhibits the BRCC3-containing isopeptidase complex (BRISC)-mediated NLRP3 deubiquitination and activation. In addition, we show that holomycin, a natural methyl derivative of THL, displays an even higher inhibitory activity against NLRP3 inflammasome than THL. Our study validates that posttranslational modification of NLRP3 can be pharmacologically targeted to prevent or treat NLRP3-associated inflammatory diseases. Future clinical development of derivatives of THL may provide new therapies for NLRP3-related diseases.
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Enzimas Desubiquitinantes/antagonistas & inibidores , Encefalomielite Autoimune Experimental/tratamento farmacológico , Inflamassomos/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Animais , Enzimas Desubiquitinantes/genética , Enzimas Desubiquitinantes/metabolismo , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/imunologia , Feminino , Sangue Fetal , Humanos , Inflamassomos/imunologia , Inflamassomos/metabolismo , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Lactamas/farmacologia , Lactamas/uso terapêutico , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/imunologia , Gravidez , Cultura Primária de Células , Pirrolidinonas/farmacologia , Pirrolidinonas/uso terapêutico , Células THP-1 , Ubiquitinação/efeitos dos fármacosRESUMO
Objective:Cardiopulmonary resuscitation quality index (CQI) is based on pulse oximetry plethysmographic waveform (POP), which have been proved able to reflect the peripheral circulation state as good as the quality of chest compression during cardiopulmonary resuscitation (CPR). It has been confirmed that CQI is as good as the partial pressure of end-tidal carbon dioxide (P ETCO 2) in prognostic evaluation of CPR patients. The purpose of this study was to explore whether advanced airway establishment affects the prognostic value of CQI during CPR. Methods:This was a prospective descriptive study. 376 patients receiving CPR were divided into advanced airway group and non-advanced airway group according to whether advanced airway was established, each of which was divided into ROSC (return of spontaneous circulation) group and non-ROSC group according to whether they got ROSC. The changes of CQI and P ETCO 2 during CPR were collected, and the relation of these parameters and the prognosis of patients was analyzed. Results:In advanced airway group, both CQI [(63.3±20.7) vs (49.7±23.8)] and P ETCO 2 [(19.8 (11.4, 31.6) vs 8.8 (3.3, 15.8)] mmHg were statistically different between ROSC group and non-ROSC group ( P <0.05). The cut-off value for these two parameters were 60.4 and 16.3 mmHg respectively. There was no significant difference between the two curves ( P>0.05). In the non-advanced airway group, CQI [(63.0±21.8) vs (42.2±29.0)] were also statistically different between the ROSC group and the non-ROSC group ( P <0.05). The cut-off value of CQI in advanced airway group and non-advanced airway group were 60.4 and 61.1, respectively. And there was no statistical difference between the two curves ( P>0.05). Conclusions:During CPR, CQI can be used to evaluate the prognosis of patients, which is as good as that of P ETCO 2. Establishment of advanced airway does not affect the prognostic evaluation of CQI during CPR.
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Objective To investigate the correlation between TRIM29 expression and non-small cell lung cancer (NSCLC) and its different histological types and clinicopathological features. Methods Using computer retrieves data databases such as PubMed, EMbase, China Knowledge Network and Wanfang Data, and collects relevant case-control studies at home and abroad. The time for searching the literature is as of August 1, 2018. Meta-analysis of the relationship between TRIM29 positive expression and clinicopathological features and tissue typing of non-small cell lung cancer was conducted by Review Manager 5.3 software. Results Five studies were included, including 1061 in the NSCLC group and 918 in the control group. Meta-analysis showed statistically significant differences between the expression of TRIM29 between NSCLC group and the control group [OR=18.32, 95%CI (4.62, 72.67), P<0.0001], squamous cell carcinoma and adenocarcinoma group [OR=37.05, 95%CI (2.45, 559.73), P=0.009], NSCLC lymph node metastasis group and NSCLC lymph node without metastasis group [OR=5.62, 95%CI (2.83, 11.17), P<0.00001], NSCLC (Ⅰ+Ⅱ) and (Ⅲ+Ⅳ) [OR=0.18, 95%CI (0.10, 0.32), P<0.00001] and NSCLC well differentiated group and the NSCLC middle and low differentiated group [OR=0.12, 95%CI (0.07, 0.21), P<0.00001], respectively. Conclusions The expression of TRIM29 is significantly correlated with NSCLC and its histological classification, lymph node metastasis, clinical stage and histological grade. This paper has certain help and reference value for the histological and clinical pathological features of NSCLC patients.
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Objective To investigate the clinical efficacy and ultrasonographic changes treated with anti-thyroid drugs ( ATD ) in patients with primary hyperthyroidism(PHT).Methods 83 cases of PHT patients admitted to the department of ultrasound from February 2013 to August 2015 in Zhuji People's Hospital of Zhejiang Province were selected, the patients were divided into two groups according to the results of ultrasonography, echo nonuniform group 41 cases and echo uniform group 42 cases.ATD therapy was administered to the both groups (were treated with methimazole).The thyroid related indexes and hemodynamics of thyroid right superior diagnosed by color doppler ultrasound, and the curative efficacies of the two groups were analyzed.Results After treatment, the systemic vascular resistance index(RI) of echo uniform group was (0.62 ±0.17), and the echo nonuniform group was (0.65 ±0.18), there was no significant difference between the two groups.The echo uniform group of thyroid artery diameter on the right lobe(D), the peak systolic velocity(Vmax), minimum diastolic blood flow velocity(Vmin), thyroid volume(V) and blood flow volume(Q) were significantly lower than the echo nonuniform group, the difference was statistically significant (P <0.05).The total effective rate of the echo nonuniform group (48.78%) was significantly lower than that in the echo uniform group (85.71%), the difference was statistically significant(P <0.05).Conclusion ATD has a good effect in treating PHT, and can significantly improve the thyroid hemodynamics in patients, it has a positive effect on the regulation of thyroid-related parameters in patients, the clinical treatment is effective, and the effect is better especially in patients with uniform echo.
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@#BACKGROUND: Although regulatory T cells (Tregs) are key to the maintenance of immunologic homeostasis and tolerance, little is known about Treg-mediated immunosuppression in the stage of sepsis. This article aimed to review the current literature on the role of Tregs in the pathophysiology of septic response, attempting to investigate the role of Tregs in immune dysfunction during sepsis. DATA SOURCES: A literature search was conducted in January 2014 using the China National Knowledge Infrastructure and PubMed. Articles on the role of Tregs in immune dysfunction during sepsis were identified. RESULTS: The identified articles indicated that Treg levels can be used for the assessment of the course of sepsis. The inhibition of Treg activity can promote the recovery of immune function. CONCLUSION: Since the mechanism of Tregs is complex during the sepsis, more studies are needed.
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Background and purpose:Myelosuppression is the most common dose-limiting toxicity of tumor chemotherapy in which leukocytopenia and neutropenia are the most common conditions. Not only are up-titrations of the doses of chemotherapeutic drugs limited, but also normal process of the chemotherapy is affected. Filgrastim-Recombinant Human Granulocyte Colony-Stimulating Factor (rhG-CSF) has the activity of stimulating the formation of granulocyte colony and promoting the growth, proliferation and differentiation of granulocytes which can be signiifcantly effective on leukocytopenia and neutropenia induced by chemotherapy. In this study, we observed the leukogenic effects, toxic and side effects of low, medium, and high doses of rhG-CSF used prophylactically after chemotherapy in patients with advanced non-small cell lung cancer (NSCLC), to explore a rational application strategy for rhG-CSF..Methods:One hundred and twenty six patients with pathologically proved advanced non-small cell lung cancer (NSCLC) under chemotherapy were digitally randomized to A, B and C groups. Filgrastim was given to patients of the three groups 24h after the end of chemotherapy. The dosages are: Group A (low dose): 300 μg of Filgrastim, s.c., qd × 1 day; Group B (medium dose): 300 μg of Filgrastim, s.c., qd × 2 days; Group C (high dose): 300 μg of Filgrastim, s.c., qd × 3 days. Then the signs and symptoms as well as toxic and side effects of Filgrastim after medication were observed.Results:Prophylactic usage of medium and high dosages of rhG-CSF could maintain WBC count at no less than 4.0×109/L in nearly 60% of patients. In patients with Grade III leukopenia, more days were needed for recovery of white blood cell (WBC) count with the low dose, while signiifcantly (P<0.05) less days were needed with the high dose. In view of the dynamic changes of neutrophil(ANC), additioning of the high dose of rhG-CSF after chemotherapy could increase the average level ofANC, notably shortening the duration of lowANC caused by chemotherapy. The incidence of infections was 4.76% for the 126 patients as a whole, 9.52% for the low dose group, and 4.76% for the middle dose group. The patients could tolerate the slight side effects incurred during treatment with Filgrastim.Conclusion:All of the three doses (low, medium, and high) of prophylactic administration of Filgrastim after chemotherapy can promote recoveries of WBCs and neutrophil granulocytes and reduce opportunities of infections. High doses of rhG-CSF can be faster and safer in increasing WBCs and neutrophil granulocytes.
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BACKGROUND:This study was undertaken to observe the characteristics of blood pressure variability (BPV) and sepsis and to investigate changes in blood pressure and its value on the severity of illness in patients with sepsis. METHODS:Blood parameters, APACHE Ⅱ score, and 24-hour ambulatory BP were analyzed in 89 patients with sepsis. RESULTS:In patients with APACHE Ⅱ score>19, the values of systolic blood pressure (SBPV), diasystolic blood pressure (DBPV), non-dipper percentage, cortisol (COR), lactate (LAC), platelet count (PLT) and glucose (GLU) were significantly higher than in those with APACHE Ⅱ score ≤19 (P<0.05 ), whereas the values of procalcitonin (PCT), white blood cell (WBC), creatinine (Cr), PaO2, C-reactive protein (CRP), adrenocorticotropic hormone (ACTH) and tumor necrosis factor α(TNF-α) were not statistically significant (P>0.05). Correlation analysis showed that APACHE Ⅱ scores correlated significantly with SBPV and DBPV (P<0.01, r=0.732 and P<0.01, r=0.762). SBPV and DBPV were correlated with COR (P=0.018 and r=0.318; P=0.008 and r=0.353 respectively). However, SBPV and DBPV were not correlated with TNF-α, IL-10, and PCT (P>0.05). Logistic regression analysis of SBPV, DBPV, APACHE Ⅱ score, and LAC was used to predict prognosis in terms of survival and non-survival rates. Receiver operating characteristics curve (ROC) showed that DBPV was a better predictor of survival rate with an AUC value of 0.890. However, AUC of SBPV, APACHE Ⅱ score, and LAC was 0.746, 0.831 and 0.915, respectively. CONCLUSIONS:The values of SBPV, DBPV and non-dipper percentage are higher in patients with sepsis. DBPV and SBPV can be used to predict the survival rate of patients with sepsis.
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<p><b>BACKGROUND</b>Osteoarthritis (OA) is the most common form of human polyarthritis. Many genetic factors have been implicated in OA. It was reported that a polymorphism in the gene of interleukin-6 (IL-6) was associated with OA of knee. The aim of this study was to determine whether functional IL-6 promoter -174G/C (rs1800795) polymorphisms confer susceptibility to knee OA.</p><p><b>METHODS</b>A meta-analysis was conducted on the association between the IL-6 polymorphism and knee OA. Electronic search at PubMed, EMBASE, Weipu database, and Wanfang database was conducted to select studies. Case-control studies containing available genotype frequencies of IL-6 -174G/C were chosen, and odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of this association.</p><p><b>RESULTS</b>A total of seven studies involving 6 464 subjects (knee OA 3 331 and controls 3 133) were considered in this study. The results suggested that the variant genotypes were not associated with knee OA risk in all genetic models (additive model: OR = 1.144, 95% CI 0.934-1.402, P = 0.194; recessive model: OR = 1.113, 95% CI 0.799-1.550, P = 0.526; dominant model: OR = 1.186, 95% CI 0.918-1.531, P = 0.191). A symmetric funnel plot, the Begg's test (P > 0.05), suggested that the data lacked publication bias.</p><p><b>CONCLUSIONS</b>This meta-analysis does not support the idea that rs1800795 genotype is associated with increased risk of knee OA. However, to draw comprehensive and more reliable conclusions, further prospective studies with larger numbers of participants worldwide are needed to examine the association between rs1800795 polymorphism and knee OA.</p>
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Humanos , Interleucina-6 , Genética , Osteoartrite do Joelho , Epidemiologia , Genética , Polimorfismo Genético , Genética , Regiões Promotoras Genéticas , GenéticaRESUMO
Objective To observe the features of a rare Miao pedigree of Bardet-Biedl syndrome in Yunnan province and to reserve its gene. Methods Three patients of this pedigree were reported. Their clinical and biochemical features were compared with those of the other pedigree members. Lymphocytes from main members of this pedigree were collected and transformed with cyclosporine A methods. Immortalized B lymphocyte strains were checked by means of chromosome karyotype analysis. Results Patients of this pedigree demonstrated typical clinical characteristics of this syndrome with increased body weight, blood pressure, fasting glucose, and lipoprotein(a)as compared with the other pedigree members(P<0. 05). The chromosome karyotype of the lymphocytes before and after transformation was kept consistent. Conclusions Patients of this Miao pedigree showed typical clinical characteristics of this syndrome as well as abnormal metabolic features. Immortalized B lymphocyte strains with their genetic information were set successfully.
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<p><b>OBJECTIVE</b>To establish immortalized lymphoblastoid cell lines of a Miao core pedigree with Bardet-Biedl syndrome (BBS), in order to provide a long-term source of material for research.</p><p><b>METHODS</b>With Epstein-Barr virus transformation of B cells and addition of cyclosporine A to inhibit the activity of T cells, fresh anticoagulated blood samples with heparin were collected from 12 members of the core pedigree, and were used to establish the immortalized lymphoblastoid cell lines of B lymphocytes.</p><p><b>RESULTS</b>Twelve immortalized lymphoblastoid cell lines of the core BBS pedigree were obtained successfully.</p><p><b>CONCLUSION</b>The immortalized B lymphoblastoid cell lines of the Miao pedigree with BBS can preserve the whole genome information and provide long-term research materials for BBS study.</p>
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Humanos , Linfócitos B , Biologia Celular , Síndrome de Bardet-Biedl , Sangue , Genética , Linhagem Celular , Linhagem Celular Transformada , Transformação Celular Viral , China , Etnologia , Etnicidade , Genética , Herpesvirus Humano 4 , LinhagemRESUMO
Background and purpose. Chemotherapy is a standard treatment for patients with advanced stage non-small cell lung cancer (NSCLC) However, platinum based chemotherapeutic regimen haves high toxicity profile to normal tissues. Lobaplatin (LBP) is a new third-generation antitumour platinum drug. Studies abroad have shown that Iobaplatin has an anticancer activity similar to cisplatin with better tolerance and is more effective for those who are resistant to cisplatin. This study was aimed to observe the effectiveness and toxicities of lobaplatin combined with vinorelbine (NVB) for the treatment of advanced NSCLC. Methods: Sixty-four patients pathologically diagnosed as clinical stage Ⅲ_B-Ⅳ NSCLC who did not receive treatment before, were randomly assigned to two groups. NL group (NVB+LBP): LBP at a dose of 30 mg/m~2 intravenous infusion on day 1, and NVB at a dose of 25 mg/m~2 intravenous infusion on days 1 and 8. NP group (NVB+DDP): Cisplatin (DDP) at a dose of 30 mg/m~2 intravenous infusion on day 1, 2 and 3 and NVB at a dose of 25 mg/m~2 intravenous infusion on days 1 and 8. Treatments were repeated every 21-28 days for 3 cycles. Results: For 34 patients of NL group, there were CR (1 cases), PR(13 cases), NC(15 cases), and PD(5 cases). The overall response rate (RR) was 41.2%, disease control rate (DCR) was 85.3%. In NP group: RR was 43.3%, DCR was 83.3% (X~2=0.05, P>0.05). Median overall survival time was 8.6 months and 8.9 months for NL group and NP group, respectively. The main toxicities in NL group were myelosuppression. Digestive toxicity such as anorexia, nausea,vomiting were less than those in the NP group (X~2=7.43, P<0.05), Peripheral hour,toxicity, serious liver and renal toxicity were not observed in NL group. Conclusion: Compared with cisplatin plus vinorelbine, domestic lobaplatin with vinorelbine yielded similar efficacies for NSCLC, but had less toxicity and well tolerate.
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<p><b>OBJECTIVE</b>To investigate the differential gene expression profile from patients with Bardet-Biedl syndrome (BBS) by oligonucleotide microarray technique.</p><p><b>METHODS</b>Total RNA of 3 probands with BBS and 4 healthy siblings were isolated from peripheral blood mononuclear cells and reverse-transcribed to cDNAs. Then the cDNAs were subjected for microarray screening with Affymetrix U133 Plus 2.0 array. Genechip scanner was applied to screen the hybridization signals. Genes differentially expressed between the BBS probands and controls were identified by using GCOS1.4 software with the standard of two-fold change (P<0.05) of expression.</p><p><b>RESULTS</b>Fifteen genes were up-regulated 2 or more fold and another 15 genes were down-regulated 2 or more fold in the BBS patients, among them 12 genes were related to signaling pathway and cell cycle by Gene Ontology (GO) analysis.</p><p><b>CONCLUSION</b>The differentially expressed genes identified may correlate with the function or structure of cilia. Their roles in the BBS genesis need to be further studied.</p>
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Adulto , Feminino , Humanos , Masculino , Síndrome de Bardet-Biedl , Genética , Metabolismo , Células Cultivadas , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Leucócitos Mononucleares , Metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , IrmãosRESUMO
<p><b>OBJECTIVE</b>To probe into the effect of electroacupuncture (EA) at Shuigou (GV 26) on mild and moderate shock.</p><p><b>METHODS</b>With 3-center randomized control study method, 276 cases were assigned to an EA plus medicine group and a medication group, 138 cases in each group. They were treated respectively with western medicine plus EA at Shuigou (GV 26), and simple western medicine. Their curative effects were observed after treatment for 6 hours.</p><p><b>RESULTS</b>The blood pressure was immediately increased in the EA plus medicine group and the increase of blood pressure was earlier than that in the medication group (P<0.001). The markedly effective rate of 52.9% in the EA plus medicine group was significantly higher than 18.1% in the medication group (P<0.001).</p><p><b>CONCLUSION</b>The therapeutic effect of EA at Shuigou (GV 26) plus western medicine on mild and moderate shock is better than that of simple western medicine.</p>