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Biosimilars are biological medicinal products that are highly similar to an already licensed reference product in terms of quality, safety, and efficacy. BAT1706 is being developed by Bio-Thera Solutions, Ltd. as a proposed biosimilar candidate to bevacizumab reference product (Avastin®). Bevacizumab acts by specifically binding to vascular endothelial growth factor A (VEGF-A), and preventing the interaction of VEGF-A with its receptors on the surface of endothelial cells, then blocking the downstream signaling pathway mediated by ligand-receptor, and inhibiting endothelial angiogenesis, thus inhibiting tumor growth. Comprehensive analytical characterization studies incorporating orthogonal analytical techniques were performed to compare the in vitro functional activities of BAT1706 and Avastin®. BAT1706 and Avastin® showed highly similar binding activity to multiple VEGF-A isoforms and equivalent VEGF-A neutralizing activity, as well as inhibitory activity of VEGF receptor (VEGFR)-2 tyrosine kinase autophosphorylation. Both products exhibited similar binding of the Fcγ receptors and a lack of Fc-related effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Overall, the results demonstrate that BAT1706 and Avastin® are highly similar in terms of in vitro functional activities.
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Azoospermia patients who carry a monogenetic mutation that causes meiotic arrest may have their biological child through genetic correction in spermatogonial stem cells (SSCs). However, such therapy for infertility has not been experimentally investigated yet. In this study, a mouse model with an X-linked testis-expressed 11 (TEX11) mutation (Tex11
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Animais , Masculino , Camundongos , Células-Tronco Germinativas Adultas/metabolismo , Azoospermia/genética , Infertilidade Masculina/terapia , Mutação/genética , Espermatogênese/genéticaRESUMO
Objective • To find out the optimal positive end expiratory pressure (PEEP) by electrical impedance tomography (EIT) for better lung recruitment and ventilation distribution in patients undergoing off pump coronary artery bypass grafting surgery (OPCAB). Methods • 105 patients underwent OPCAB from Jan. 2017 to Dec. 2017 were analysed. Patients were randomly divided into two groups, i.e. experiment group (54 cases) and control group (51 cases). Four regions of interest (ROI) were recorded by EIT. PEEP were 3 cmH2O in control group while PEEP were increased stepwise by 2 cmH2O from 0 cmH2O to 14 cmH2O in experiment group. The optimal PEEP for lung recruitment was applied in experiment group. Postoperative oxygenation index (PaO2/FiO2) and pulmonary complication were compared between two groups. Results • The overall mortality was 2 (1.90%). The incidence of postoperative pulmonary complication, pulmonary infection, atelectasis, pleural effusion were 18.10%, 2.86%, 18.10%, 18.10%, respectively. The optimal PEEP zone was 6-9 cmH2O. PaO2/FiO2 was significantly increased with the optimal PEEP in experiment group (P=0.00). There were significant differences in postoperative pulmonary complication between two groups (P=0.02). Conclusion • EIT can directly monitor ventilation distribution and titrate suitable PEEP for better lung recruitment in patients undergoing OPCAB. It can significantly reduce postoperative pulmonary complication, improve oxygenation, and decrease ICU stay and ventilation duration.
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Objective·To find out the optimal positive end expiratory pressure (PEEP) by electrical impedance tomography (EIT) for better lung recruitment and ventilation distribution in patients undergoing off pump coronary artery bypass grafting surgery (OPCAB). Methods?·?105 patients underwent OPCAB from Jan. 2017 to Dec. 2017 were analysed. Patients were randomly divided into two groups, i.e. experiment group (54 cases) and control group (51 cases). Four regions of interest (ROI) were recorded by EIT. PEEP were 3?cmH2O in control group while PEEP were increased stepwise by 2?cmH2O from 0?cmH2O to 14?cmH2O in experiment group. The optimal PEEP for lung recruitment was applied in experiment group. Postoperative oxygenation index (PaO2/FiO2) and pulmonary complication were compared between two groups. Results?·?The overall mortality was 2 (1.90%). The incidence of postoperative pulmonary complication, pulmonary infection, atelectasis, pleural effusion were 18.10%, 2.86%, 18.10%, 18.10%, respectively. The optimal PEEP zone was 6-9?cmH2O. PaO2/FiO2was significantly increased with the optimal PEEP in experiment group (P=0.00). There were significant differences in postoperative pulmonary complication between two groups (P=0.02). Conclusion?·?EIT can directly monitor ventilation distribution and titrate suitable PEEP for better lung recruitment in patients undergoing OPCAB. It can significantly reduce postoperative pulmonary complication, improve oxygenation, and decrease ICU stay and ventilation duration.
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This study is to construct a rapid and effective method for identification of wild and cultivated Glycyrrhiza uralensis (hereinafter referred to as Glycyrrhizae Radix et Rhizoma) from Ningxia by comparison of the difference in chromatography identification based on index components and near-infrared spectroscopy identification. HPLC and UV methods were used to determine the content of liquiritin, glycyrrhizate and total flavonoids for 9 wild Glycyrrhizae Radix et Rhizoma and 14 cultivated Glycyrrhizae Radix et Rhizoma samples,and the near-infrared spectroscopy was also,collected. The results illustrated that the chromatography identification based on index components could not identify wild and cultivated Glycyrrhizae Radix et Rhizoma from Ningxia, while near-infrared spectroscopy could quickly and effectively achieve it. It provides an effective method for the growth pattern identification and application of Glycyrrhizae Radix et Rhizoma.
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The distribution information of Glycyrrhiza uralensis was collected by interview investigation and field survey, and 46 related environmental factors were collected, some kinds of functional chemical constituents of G.uralensis were analyzed. Integrated climate, topography and other related ecological factors, the habitat suitability study was conducted based on Arc geographic information system(ArcGIS),and maximum entropy model. The AUC of ROC curve was both above 0.95, indicating that the predictive results with the maximum model were highly precise. The results showed that 5 major ecological factors have obvious influence on ecology suitability distributions of G. uralensis, including July average temperature, soil sub category, Dec precipitation, vegetation types and standard deviation of seasonal variation in temperature, et al. It is suitable for the living habits of the G. uralensis, adequate light, low rainfall, summer heat and large temperature difference between day and night, which is suitable for distribution in the northern temperate plains and mountains. In addition, the ecological suitability regionalization based on the chemical constituents of G.uralensis also provides a new suitable distribution area other than the traditional distribution area, which provides a scientific basis for the reasonable introduction of G.uralensis.
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The distribution information of Lycii Fructus was collected by interview investigation and field survey, and 46 related environmental factors were collected, some kinds of functional chemical constituents the of Lycii Fructus were analyzed. Integrated climate, topography and other related ecological factors, the habitat suitability study was conducted based on Arc geographic information system(ArcGIS),and maximum entropy model. The AUC of ROC curve was both above 0.95, indicating that the predictive results with the maximum model were highly precise. The results showed that 5 major ecological factors had obvious influence on ecology suitability distributions of Lycii Fructus, including soil pH, soil subclass, vegetation type and in August the average temperature et al. It is suitable for the living habits of the Lycii Fructus, dry, cool weather, more hardy, drought-resistant, alkali soil, which is suitable for distribution in the northern temperate plains. In addition, the ecological suitability regionalization based on the chemical constituents of Lycii Fructus also provides a new suitable distribution area other than the traditional distribution area, which provides a scientific basis for the reasonable introduction of Lycii Fructus.
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Scutellaria baicalensis is a common and important medicinal plant in China, facing with reducing sharply in wild resources. To meet the needs in Chinese herbwouls medicine market and clinical application, S. baicalensis has been widely cultivated in Ningxia, Hebei, Shanxi, and Gansu et al. HPLC finger-print and near-infrared were studied in the research to evaluate quality difference of S. baicalensis in four districts. The results showed that the similarity of HPLC finger-print of 12 cultivated S. baicalensis and reference crude herb is more than 0.961, and the other is more than 0.983. On the other hand, paired sample t-test indicated there has no significant difference between the common peaks' area of 12 cultivated S. baicalensis and reference crude herb. It was verified that 12 cultivated S. baicalensis has highly consistency with reference crude herb. On the basis of chromatographic finger-print and near-infrared spectrum, the study applied paired sample t-test to verify analysis results, which could avoid erroneous judgment induced by indefinite threshold values in the similarity of chromatographic finger-print and provide reliable basis for the analysis results. Meanwhile, it also provides a new idea for improving the quality control method of Chinese medicinal materials by comparative study about two comprehensive detection means.
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<p><b>OBJECTIVE</b>To study the inhibitory effect of flavonoids from Glycyrrhiza uralensis on thioacetamide-induced chonic hepatic fibrosis in rats and the effect on the protein expressions of transforming growth factor-β1 (TGF-β1) and Caspase-3 in livers.</p><p><b>METHOD</b>Male Sprague-Dawley rats were randomly divided into totally seven groups: the normal control group, the model group, LF groups s (400, 200, 100, 50 mg · kg(-1) · d(-1)) and the silymarin positive control group (30 mg · kg(-1) · d(-1)). The hepatic fibrosis model was induced in the rats through intraperitoneal injection with 3% thioacetamide (TAA) at a dose of 150 mg · kg(-1) body weight twice a week for 12 weeks. During the course, the control group and the model group were orally administered with saline (1 mL · kg(-1) · d(-1)). After the modeling and drug intervention, the pathologic changes and fibrosis in liver tissues were observed by HE staining and Masson's Trichrome staining. The serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and liver hydroxyproline (HYP) contents were assayed by biochemical process. The serum hyaluronic acid (HA) was assessed by radioimmunoassay. In addition, the protein expressions of liver TGF-β1 and Caspase-3 were examined by immunohistochemical method. The mRNA expression of TGF-β1 in hepatic tissues was examined by quantitative Real-time PCR analysis.</p><p><b>RESULT</b>Compared with the model group, flavonoids can protect the integrity of the structure of liver tissues, significantly reduce the hepatic cell degeneration and necrosis and the proliferation of fibrous tissues, notably reduce the serum AST, ALT, ALP and HA and HYP in hepatic tissues and down-regulate the protein expressions of liver TGF-β1 and Caspase-3 and the mRNA expression of TGF-β1 in hepatic tissues.</p><p><b>CONCLUSION</b>The licorice flavonoids can resist the thioacetamide-induced hepatic fibrosis in rats. Its mechanism may be related to the down-regulation of the protein expressions of TGF-β1 and Caspase-3.</p>
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Animais , Masculino , Ratos , Caspase 3 , Flavonoides , Farmacologia , Glycyrrhiza uralensis , Química , Ácido Hialurônico , Sangue , Fígado , Patologia , Cirrose Hepática Experimental , Metabolismo , RNA Mensageiro , Ratos Sprague-Dawley , Tioacetamida , Fator de Crescimento Transformador beta1 , GenéticaRESUMO
Adult rats chronic unpredictable stress model of depression (CUS) was adopted to elucidate the antidepressant pharmacological activity and related neurogenesis protective effect of the total flavonoids extract (licorice flavonoids, LF) from the Glycyrrhiza uralensis Fisch. cultivated locally in Ningxia. The rats were exposed to 9 kinds of unpredictable sequence of stressors and were given flavonoids (300 mg x kg(-1), 100 mg x kg(-1) and 30 mg x kg(-1)) for 28 days. The antidepressant effect was elucidated by open field test, forced swimming test and tail suspension test. The level of serum corticosterone was detected by radioimmunoassay. 5'-Bromo-2'-deoxyuridine (BrdU) labeling experiments was employed to study the neurogenesis protective activities. The flavonoids can increase the sum of line crosses and number of rears, and decrease the number of fecal boli produced in the open field test of the CUS rats. Also the flavonoids can decrease the immobility time in forced swim test as well as in the tail suspension test. In addition, the flavonoids (300 mg x kg(-1)) can decrease the serum corticosterone level of the CUS rats, and increase the number of the new born BrdU positive progenitor cells at the subgranular zone (SGZ) of dentate gyrus (DG) region in hippocampus. The results demonstrated that the total flavonoids extract from the cultivated Glycyrrhiza uralensis Fisch. could produce the anti-depressive effect on chronic unpredictable stress of depression model rats and its mechanism may be associated with its neurogenesis protective effect.
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Animais , Masculino , Ratos , Antidepressivos , Farmacologia , Comportamento Animal , Bromodesoxiuridina , Metabolismo , Corticosterona , Metabolismo , Depressão , Metabolismo , Flavonoides , Farmacologia , Glycyrrhiza uralensis , Química , Elevação dos Membros Posteriores , Hipocampo , Biologia Celular , Metabolismo , Neurogênese , Plantas Medicinais , Química , Distribuição Aleatória , Ratos Sprague-Dawley , Estresse Psicológico , Metabolismo , NataçãoRESUMO
To investigate the expression level of cyclic nucleotide phosphodiesterase (PDE) 7B mRNA and its prognostic value in mantle cell lymphoma (MCL), the real-time quantitative RT-PCR (QPCR) was used to detect pde7b expression levels of bone marrow mononuclear cells from 20 newly diagnosed MCL patients with bone marrow involvement and peripheral blood mononuclear cells from 20 normal persons, the association of pde7b expression levels with prognostic indexes was analyzed by statistical software. The results showed that the median values of pde7b mRNA expression level in 20 MCL patients and normal controls were 8.7 × 10(-4) (4 × 10(-5) - 6.9 × 10(-3)) and 0.5 × 10(-4)(0.18 × 10(-4) - 1.7 × 10(-4)) respectively (p = 0.001). No association was found between pde7b expression and patients' clinical baseline information (gender and age), as well as certain prognostic factors, leukocyte count, lactate dehydrogenase level, CD38 expression and immunoglobulin heavy-chain variable region mutation status, but pde7b mRNA expression was significantly associated with cytogenetic abnormality, β(2)-microglobulin level and ZAP-70 expression. It is concluded that the pde7b mRNA expression is obviously higher in MCL patients compared with normal controls and significantly correlates with unfavorable cytogenetic characteristics in MCL. The pde7b may be used as a novel prognostic indicator in MCL, and has important clinical significance.
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Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos de Casos e Controles , Nucleotídeo Cíclico Fosfodiesterase do Tipo 7 , Genética , Metabolismo , Linfoma de Célula do Manto , Genética , Metabolismo , Patologia , Reação em Cadeia da Polimerase , Métodos , PrognósticoRESUMO
<p><b>OBJECTIVE</b>To study the reproduction characteristic of Cistanche deserticola.</p><p><b>METHOD</b>The reproduction characteristic and growing dynamic in Ningxia plantation were investigated, the contents of boschnaloside and echinacoside were determined during reproduction period.</p><p><b>RESULT</b>The germination period of C. deserticola was in the first ten days of the month, the duration from the germination to flowering lasted about one month. The contents of boschnaloside and echinacoside decreased during reproduction period.</p><p><b>CONCLUSION</b>The reproduction period of C. deserticolais lasts about two months, germination period of C. deserticola is the suitable harvest time.</p>