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The powder modification technology was used to improve the powder properties and microstructure of Dioscoreae Rhizoma extract powder, thereby solving the problem of poor solubility of Dioscoreae Rhizoma formula granules. The influence of modifier dosage and grinding time on the solubility of Dioscoreae Rhizoma extract powder was investigated with the solubility as the evaluation index, and the optimal modification process was selected. The particle size, fluidity, specific surface area, and other powder properties of Dioscoreae Rhizoma extract powder before and after modification were compared. At the same time, the changes in the microstructure before and after modification was observed by scanning electron microscope, and the modification principle was explored by combining with multi-light scatterer. The results showed that after adding lactose for powder modification, the solubility of Dioscoreae Rhizoma extract powder was significantly improved. The volume of insoluble substance in the liquid of modified Dioscoreae Rhizoma extract powder obtained by the optimal modification process was reduced from 3.8 mL to 0 mL, and the particles obtained by dry granulation of the modified powder could be completely dissolved within 2 min after being exposed to water, without affecting the content of its indicator components adenosine and allantoin. After modification, the particle size of Dioscoreae Rhizoma extract powder decreased significantly, d_(0.9) decreased from(77.55±4.57) µm to(37.91±0.42) µm, the specific surface area and porosity increased, and the hydrophilicity improved. The main mechanism of improving the solubility of Dioscoreae Rhizoma formula granules was the destruction of the "coating membrane" structure on the surface of starch granules and the dispersion of water-soluble excipients. This study introduced powder modification technology to solve the solubility problem of Dioscoreae Rhizoma formula granules, which provided data support for the improvement of product quality and technical references for the improvement of solubility of other similar varieties.
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Tecnologia Farmacêutica , Tecnologia , Pós , Solubilidade , Extratos Vegetais , Tamanho da PartículaRESUMO
Animal medicines have been called "medicine with affinity to flesh and blood" by doctors of all ages, which always act as an important branch of Chinese medicine. They have various types, extensive sources and long application history, with unique cli-nical effects in anti-coagulation, anti-thrombosis, anti-fatigue, immune regulation, anti-tumor, anti-convulsion and so on. Most animal medicines contain proteins, fatty acids, and trimethylamine oxides, which are prone to decomposition and produce substances such as biological amines, aldehydes, ketones, alcohols, trimethylamine and ammonia with unpleasant odors. The stench produced by the combination of various odors can easily cause side effects such as nausea and vomiting, which would probably affect the drug compliance and clinical efficacy in patients, and block the development of high-quality animal medicines. At present, we have insufficient understanding on sources and formation mechanism of the stench of animal medicines, lacking development of taste-masking technology. Therefore, the universality, formation, vomiting mechanism, evaluation methods, and masking technology of stench of animal medicines were summarized in this paper, so as to deepen the recognition of stench, provide references for the development of animal medicines deodorization technology, enhance patients' compliance with animal medicines, and promote animal drugs to better serve public health in the new era.
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Neoplasias , Paladar , Animais , Fadiga , Humanos , TecnologiaRESUMO
BACKGROUND: A second allogeneic hematopoietic stem-cell transplantation and donor lymphocyte infusion using cells from the same donor is a therapeutic option in the case of stem-cell graft failure or disease relapse, but little is known about the factors associated with the CD34+ cell yields from second donations. METHODS: One-hundred healthy donors who underwent a second mobilization treatment and peripheral blood stem-cell (PBSC) collection were studied. For both mobilization processes, 5 µg of granulocyte colony-stimulating factor per kg per day was administered. The blood counts of the donors were monitored during the processes. RESULTS: The second donations from the same donors provided lower apheresis yields than did the initial collections. The number of CD34+ cells collected from normal donors after a second cycle of PBSC mobilization was associated with their steady-state lymphocyte counts and the intertransplantation interval. Female sex negatively affected the CD34+ cell yields. The cutoff value for the steady-state absolute lymphocyte count was 2.055 × 109/L. CONCLUSION: To harvest greater numbers of CD34+ cells from second collections, male donors and those with intervals of longer than 9 months between donations should be selected. The lymphocyte counts prior to the first donations may predict the content of CD34+ cells in the allografts prepared using the second donations.
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Antígenos CD34/metabolismo , Doadores de Tecidos , Adolescente , Adulto , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Células-Tronco de Sangue Periférico/citologia , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVE: To prepare andrographolide composite particles, and evaluate their particle structure and dissolution. METHOD: The mechanical crushing method was adopted to prepare andrographolide and polyethylene glycol (PEG) 6000 composite particles. The structures were characterized by the scanning electron microscope (SEM) and the differential scanning calorimeter (DSC). The contact angles were determined by the contact angle analyzer. The in vitro dissolution curve was detected. RESULT: Andrographolide and PEG 6000 gave rise to coated composite particle structures, with the decrease in the crystallinity of andrographolide. The in vitro dissolution rate of composite particles was significantly obvious than that of its raw materials, ultrafine powder and their physical mixtures. CONCLUSION: Andrographolide composite particles based on the mechanical crushing method could notably enhance the in vitro dissolution of andrographolide.
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Diterpenos/química , Medicamentos de Ervas Chinesas/química , Varredura Diferencial de Calorimetria , Química Farmacêutica/métodos , Tamanho da Partícula , Solubilidade , Torção MecânicaRESUMO
The hydrophilicity of the normal decoction pieces (NDP) of Indigo Naturalis is not good, therefore, it is not suit for decoctions. In this paper, powder modification technology is used and some NDP and alcohol are ground together in the vibromill to prepare the hydrophilic decoction pieces (HDP) of Indigo Naturalis. Initially, the properties of NDP, ultrafine decoction pieces (UDP) and HDP are compared, the hydrophilicity of UDP was promoted slightly, that of HDP is promoted dramatically. Then, three batches of Indigo Naturalis are prepared to HDP separately, but there is no obvious difference in the contact angle. Furthermore, the size distribution, surface area and micro-shape of HDP are bigger than that of UDP and smaller than NDP. The contents of indigo and indirubin in three decoction pieces are the same, as well as the species of inorganic substance, although there is a little difference in the proportion of five inorganic substances. The fact suggests the change of physical state and the qualitative and quantitative change of organism and inorganic substances are not the main factors to influence the hydrophilicity. In addition, hydroxyl, methylene and methyl can be identified at the wavenumber of 3 356 cm(-1) and 1 461 cm(-1) in infrared spectrum; the content of alcohol in HDP is 0.67% measured by gas chromatogram. The stability of HDP in the heating condition is studied, the fact suggests the hydrophilic effect of HDP at 40 degrees C is relatively stable. All above research suggests that the alcohol is the main factor to influence the hydrophilicity and maybe the intermolecular force which fixed alcohol molecule on the surface of Indigo Naturalis is the basic principle to produce the hydrophilicity.
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Interações Hidrofóbicas e Hidrofílicas , Índigo Carmim/química , Tecnologia Farmacêutica/métodos , Acanthaceae/química , Álcoois/análise , Índigo Carmim/análise , Índigo Carmim/isolamento & purificação , Indóis/análise , Isatis/química , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Plantas Medicinais/química , Polygonum/química , Pós , Propriedades de Superfície , Difração de Raios XRESUMO
OBJECTIVE: To prepare dental ulcer powder by using particle design technology, and compare the effect on the micromeritic property of dental ulcer powder with regular grinding and ultrafine grinding methods. METHOD: Above three methods were respectively used to make dental ulcer powder, in order to evaluate their difference in appearance character, grain size distribution, specific surface area and porosity, contact angle, micro-morphological character and borneol's stability. RESULT: Compared with normal powder, ultrafine powder and particle design showed increase in color uniformity and decrease in sour taste, and the particle design powder smells almost no borneol. Their grain size distributions were significantly less that of normal powder (P < 0.01), with the same grain size distribution in ultrafine powder and particle design powder. Their specific surface areas and porosities were significantly more than that of normal powder (P < 0.01), with the highest figures in ultrafine powder. Their contact angles were significantly more than that of normal powder (P < 0.01), with the highest figure in particle design powder. The surface of normal powder was smooth, with a few of small particle adhered. The surface of ultrafine powder was partially coated with small particles, where as the surface of particle design powder was mostly coated with particles. There was difference in micro-morphological character and surface attachment among the three. The 10-day accelerate stability experiment showed that normal power, ultrafine powder and particle design powder lost borneol by 90. 13% , 66. 48% and 40.57%, respectively. Particle design powder showed the highest stability, followed by ultrafine powder and normal powder. CONCLUSION: The preparation process can affect the micromeritic properties, by changing microscopic structure of the powders. We can design the macroscopic property of powder by regulating the formation of the microscopic structure with particle design technology.
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Medicina Tradicional Chinesa/métodos , Úlceras Orais/terapia , Pós , Silicones/química , Tecnologia Farmacêutica/métodos , Materiais para Moldagem Odontológica/química , Estabilidade de Medicamentos , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Material Particulado , Reprodutibilidade dos Testes , Propriedades de SuperfícieRESUMO
OBJECTIVE: To study the micromeritic properties of different particle size of Scutellaria baicalensis and provide a basis for being directly used or as raw material of Chinese herba preparation. METHODS: Size distribution, surface area and pore volume, contact angle, angle of repose and bulk density, moisture absorption, micromorphology, Infrared spectrum, HPLC fingerprint were used to evaluate the differences of micromeritic properties of 4 kinds of Scutellaria baicalensis superfine grinding. RESULTS: With the particle size of powders decreased, size distribution and bulk density decreased, the surface area and pore volume, contact angle and moisture absorption increased, angle of repose first increased and then decreased. Infrared spectrum and HPLC fingerprint showed no change of chemical composition of Scutellaria baicalensis. CONCLUSION: Different particle size of Scutellaria baicalensis leads to the differences of micromeritic properties. Superfine grinding III is determined as a better particle size.
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Medicamentos de Ervas Chinesas/química , Pós , Scutellaria baicalensis/química , Tecnologia Farmacêutica/métodos , Química Farmacêutica , Estabilidade de Medicamentos , Tamanho da Partícula , Raízes de Plantas/química , Reprodutibilidade dos Testes , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de SuperfícieRESUMO
Bamboo charcoal, a type of manufactured biochar, is produced by pyrolyzing bamboo residue under anoxic conditions. Its beneficial properties in absorption, catalyst support, and agricultural function have attracted significant attention; however, relatively few studies have examined its effects on the soil microbiota. In this study, we analyzed the effects of bamboo charcoal on soil physicochemical properties, enzymes, and microbial community structure in tea plantations and investigated the optimal amount of bamboo charcoal to be added to organic fertilizer. The results show that bamboo charcoal can further increase soil available nitrogen, total and available phosphorus and potassium, organic carbon content, pH, and urease activity. However, only the combined use of bamboo charcoal and organic fertilizer significantly increased total nitrogen, sucrase, and ß-glucosidase activities in the soil. Bamboo charcoal also significantly increased the Chao1 and Shannon indices of microbiota diversity in a concentration-dependent manner. The structure of the bacterial community changed significantly after the bamboo charcoal addition, with Proteobacteria, Actinobacteria, and Firmicutes increasing and Acidobacteria decreasing. This study provides fundamental insights into the suitability of bamboo charcoal application for the ecological remediation of diseased soils.
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OBJECTIVE: To explore the relationship between the causes and length of posterior malleolar fragment and treatment strategies of adult patients with three types of ankle joint injury. METHODS: The investigators recruited 233 cases of type C injury, 35 cases of type B injury and 91 cases of type A injury. Type A injury referred to simple ankle joint fracture with the involvement of posterior malleolar fragment. Type B injury tibial shaft fracture with ipsilateral ankle joint fracture. And posterior malleolar fracture line was the continuity of tibial shaft fracture line. Type C injury appeared similar to Type B injury, but tibial and malleolar fracture lines were not continued. The ratio between the length of posterior malleolar articular and the total length of articular surface was calculated in theses three types of injuries in sagittal CT scan slice. Different treatment regimens were used to manage the posterior malleolar fractures. And visual analogue score (VAS) was introduced to assess the therapeutic outcomes. RESULTS: The ratio between the length of posterior malleolar articular and the total length of articular surface decreased from Type A to Type C (χ(2) = 187.453, P = 0.0000). The ratio was (34 ± 15)% for Type A, (30 ± 9)% for Type B and (12 ± 10)% for Type C. A follow-up study was performed in Type A injury (n = 58), Type B injury (n = 31) and Type C injury (n = 167) at 12 months. According to VAS score, there was no significant difference between the patients undergoing fixation and not (all P > 0.05). CONCLUSION: Different causes of posterior malleolar fracture results in different sizes of posterior malleolar fragment and strategies of treatment. The anatomic reduction of posterior malleolar fragment remains a key aspect of achieving satisfactory outcomes in all kinds of injury.
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Traumatismos do Tornozelo/cirurgia , Fraturas Ósseas/cirurgia , Fraturas da Tíbia/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Articulação do Tornozelo/cirurgia , Feminino , Fraturas Ósseas/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
NK-lysins (NKLs) are a family of multifunctional antimicrobial peptides that have activity against various microorganisms. However, the immunomodulatory activity of NKL in fish remains unclear. In this study, the cDNA sequence of barbel steed (Hemibarbus labeo) NKL gene was cloned. Barbel steed NKL amino acid sequence comprised a signal peptide and a mature peptide. The saposin B domain in the mature peptide has six conserved cysteines that form three disulfide bonds. Phylogenetic analysis showed that the barbel steed NKL was most closely related to that of the common carp (Cyprinus carpio) NKL. Differential expression analysis showed that the barbel steed NKL gene was expressed in all tested tissues, with the highest expression in the spleen. In response to Aeromonas hydrophila infection, NKL was significantly upregulated in the liver, spleen, head kidney, and gill. The barbel steed NKL showed strong antibacterial activity against Vibrio parahaemolyticus, V. alginolyticus, V. vulnificus, and Listeria monocytogenes. However, NKL had no antibacterial activity against the pathogenic bacteria A. hydrophila. Lactate dehydrogenase release assays showed that NKL damaged the V. parahaemolyticus cell membrane. NKL significantly increased barbel steed survival rate after A. hydrophila infection and upregulated IL-1ß and TNF-α expression in the spleen and head kidney. NKL induced monocyte/macrophage chemotaxis and enhanced the respiratory burst and proinflammatory cytokine expression. Our study shows that fish NKL exhibits immunomodulatory effects and protects the host from pathogenic infections independent of direct bacterial clearance.
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Aeromonas hydrophila/imunologia , Carpas/imunologia , Infecções por Bactérias Gram-Negativas/imunologia , Macrófagos/imunologia , Monócitos/imunologia , Proteolipídeos/imunologia , Sequência de Aminoácidos/genética , Animais , Carpas/microbiologia , Membrana Celular/patologia , Quimiotaxia/imunologia , Clonagem Molecular , Infecções por Bactérias Gram-Negativas/prevenção & controle , Rim Cefálico/metabolismo , Imunomodulação/imunologia , Interleucina-1beta/metabolismo , Listeria monocytogenes/imunologia , Domínios Proteicos/genética , Proteolipídeos/genética , Baço/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Vibrio/imunologiaRESUMO
BACKGROUND: This study aimed to evaluate the effects of different iterative reconstruction (IR) algorithms on coronary artery calcium (CAC) score quantification using the reduced radiation dose (RRD) protocol in an anthropomorphic phantom and in patients. METHODS: A thorax phantom, containing 9 calcification inserts with varying hydroxyapatite (HA) densities, was scanned with the reference protocol [120 kv, 80 mAs, filtered back projection (FBP)] and RRD protocol (120 kV, 20-80 mAs, 5 mAs interval) using a 256-slice computed tomography (CT) scanner. Raw data were reconstructed with different reconstruction algorithms [iDose4 levels 1-7 and iterative model reconstruction (IMR) levels 1-3]. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and Agatston score (AS) were calculated for each image series. The correction factor was derived from linear regression analysis between the reference image series and other image series with different parameters. Additionally, 40 patients were scanned with the RRD protocol (50 mAs) and reconstructed with FBP, iDose4 level 4, and IMR level 2. AS was calculated for the 3-group image series, and was corrected by applying a correction factor for the IMR group. The agreement of risk stratification with different reconstruction algorithms was also analyzed. RESULTS: For the phantom study, the iDose4 and IMR groups had significantly higher SNR and CNR than the FBP group (all P<0.05). There were no significant differences in the total AS after comparing image series reconstructed with iDose4 (level 1-7) and FBP (all P>0.05), while AS from the IMR (level 1-3) image series were lower than the FBP group (all P<0.05). The tube current of 50 mAs was determined for the clinical study, and the correction factor was 1.14. For the clinical study, the median AS from the iDose4 and IMR groups were both significantly lower compared to the FBP image series [(112.89 (63.01, 314.09), 113.22 (64.78, 364.95) vs. 118.59 (65.05, 374.48), both P<0.05]. After applying the correction factor, the adjusted AS from the IMR group was not significantly different from that of the FBP group [126.48 (69.62, 355.85) vs. 118.59 (65.05, 374.48), P=0.145]. Moreover, the agreement in risk stratification between FBP and IMR improved from 0.81 to 0.85. CONCLUSIONS: The RRD CAC scoring scan using the IMR reconstruction algorithm is clinically feasible, and a correction factor can help reduce the AS underestimation effect.
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OBJECTIVE: To investigate the association between metabolic syndrome (MS) and the incidence of atrial fibrillation (AF) in essential hypertensive (EH) patients without left ventricular hypertrophy. METHODS: A total of 972 EH without left ventricular hypertrophy were divided into EH + non MS group (n = 606) and EH + MS group (n = 366). Incidence of AF were compared between two groups. RESULTS: (1) Incidence of AF in EH + MS group was significantly higher than that in EH + non MS group (12.84% vs. 6.93%, P < 0.01). (2) Left atrial diameter (LAD), left ventricular end-diastolic diameter (LVEDd), interventricular septum thickness (IVS), left ventricular posterior wall thickness (LVPW) and left ventricular mass (LVM) were all significantly higher in EH + MS group than those in EH + non MS group (all P < 0.01) while left ventricular mass index (LVMI) and ejection fraction (EF) were similar between two groups. (3) Logistic regression analysis showed age, hypertension duration, LAD, LVEDd and MS were significantly correlated with incidence of AF in EH patients (OR: 1.683, 1.308, 2.262, 3.848 and 1.853, P < 0.05) and obesity was the independent predictor for incidence of AF (OR: 1.706, P = 0.029). CONCLUSION: MS was associated with increased incidence of AF in EH patients without left ventricular hypertrophy in this cohort.
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Fibrilação Atrial/etiologia , Hipertensão/fisiopatologia , Síndrome Metabólica/fisiopatologia , Idoso , Feminino , Humanos , Hipertensão/complicações , Hipertrofia Ventricular Esquerda , Incidência , Masculino , Síndrome Metabólica/complicações , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Interleukin-1ß (IL-1ß) is a pivotal proinflammatory cytokine that plays important roles in regulating immune responses and in inducing a series of inflammatory reactions in response to infection. Recently, increasing attention has focused on the regulatory mechanisms of IL-1ß activity in teleosts. In this regard, IL-1 receptor type 1 plays a crucial role in immune responses, whereas IL-1 receptor type 2 is a decoy receptor that functions as an IL-1ß signaling inhibitor. However, the interactions of these three proteins with respect to fish immunity have rarely been studied. In the present study, cDNAs of the il1b, il1r1, and il1r2 genes of the barbel steed (Hemibarbus labeo) were cloned and sequenced. Amino acid sequence analysis revealed that the IL-1ß protein and its two receptors identified in barbel steed are conserved in most teleosts, whereas phylogenetic tree analysis indicated that these three proteins are closely related to those of cyprinids. In response to lipopolysaccharide treatment, expression of the genes encoding IL-1ß and its two receptors was significantly upregulated in the immune-related tissues of barbel steed. Furthermore, expression of the il1r1 and il1r2 genes was induced in monocytes/macrophages in response to stimulation with recombinant IL-1ß.
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Cyprinidae/metabolismo , Proteínas de Peixes/metabolismo , Interleucina-1beta/metabolismo , Receptores de Interleucina-1/metabolismo , Sequência de Aminoácidos , Animais , Células Cultivadas , Cyprinidae/genética , Proteínas de Peixes/genética , Perfilação da Expressão Gênica , Interleucina-1beta/genética , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Monócitos/citologia , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Filogenia , Receptores de Interleucina-1/genética , Homologia de SequênciaRESUMO
Motile sperm domain containing 2 (MOSPD2) is a single-pass membrane protein to which until recently little function had been ascribed. Although its mammalian homologs have been identified, the status of the mospd2 gene in lower vertebrates is still unknown. In the present study, cDNA of the mospd2 gene of barbel steed (Hemibarbus labeo) was cloned and sequenced to characterize its potential involvement in the innate immune system of this fish. Sequence analysis revealed that the predicted barbel steed MOSPD2 protein contained an N-terminal extracellular portion composed of a CRAL-TRIO domain, a motile sperm domain, and a transmembrane domain, as well as a short C-terminal intracellular domain. Phylogenetic tree analysis indicated that barbel steed MOSPD2 is closely related to that of zebrafish. Barbel steed mospd2 transcripts were detected in a wide range of tissues, with the highest level being found in the gill. In response to lipopolysaccharide (LPS) treatment or Aeromonas hydrophila infection, mospd2 gene expression was significantly altered in the head kidney, spleen, and mid-intestine. The expression of mospd2 gene was detected in monocytes/macrophages (MO/MФ), neutrophils, and lymphocytes, and was found to be mainly expressed in MO/MФ. At the same time, using flow cytometry, we also confirmed that MOSPD2 protein is located on MO/MФ, neutrophil, and lymphocyte membranes. Following treatment with LPS or A. hydrophila, MOSPD2 protein expression was induced in these immune cells. The migration of MO/MФ and neutrophils decreased significantly upon MOSPD2 blockade with anti-MOSPD2 IgG in a dose-dependent manner, whereas this treatment had no significant effect on lymphocytes migration. To the best of our knowledge, our study, for the first time, provides evidence that MOSPD2 mediates the migration of MO/MФ and neutrophils in a fish species.
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Quimiotaxia/fisiologia , Cyprinidae/fisiologia , Proteínas de Peixes/fisiologia , Proteínas de Membrana/fisiologia , Aeromonas hydrophila/imunologia , Animais , Clonagem Molecular , Cyprinidae/genética , Cyprinidae/imunologia , Doenças dos Peixes/genética , Doenças dos Peixes/imunologia , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Macrófagos/fisiologia , Proteínas de Membrana/genética , Monócitos/fisiologia , Neutrófilos/fisiologia , Análise de Sequência de DNARESUMO
OBJECTIVE: To investigate the effect of other gene mutations outside the fusion gene on the first complete remission (CR1) induced by one course of induction chemotherapy in patients with core binding factor-associated acute myeloid leukemia (CBF-AML). METHODS: DNA was extracted from bone marrow or peripheral blood samples of newly diagnosed CBF-AML patients admitted to the Hematology Department of the Second Hospital of Shanxi Medical University from January 2015 to January 2019. Next-generation sequencing was used for detection of 34 kinds of hematologic malignancy-related gene mutations in patients with CBF-AML, the effect of related gene mutations on the first complete remission (CR1) rate in one course of induction chemotherapy was analyzed by combineation with clinical characteristics. RESULTS: 34 kinds of genes in bone marrow or peripheral blood of 43 patients were detected by high throughput sequencing and the gene mutations were detected in 16 out of 34 genes. The mutation rate of KIT gene was the highest (48.8%), followed by NRAS (16.3%), ASXL1 (16.3%), TET2 (11.6%), CSF3R (9.3%), FLT3 (9.3%), KRAS (7.0%). The detection rates of mutations in different functional genes were as follows: genes related with signal transduction pathway (KIT, FLT3, CSF3R, KRAS, NRAS, JAK2, CALR, SH2B3, CBL) had the highest mutation frequency (72.1% (31/43); epigenetic modification gene mutation frequency was 30.2% (13/43), including ASXL1, TET2, BCOR); transcriptional regulation gene mutation frequency was 7.0% (3/43), including ETV6, RUNX1, GATA2). Splicing factor related gene mutation frequency was 2.3% (1/43), including ZRSR2). The CR1 rate was 74.4% after one course of induction chemotherapy. At first diagnosis, patients with low expression of WT1 (the median value of WT1 was 788.9) were more likely to get CR1 (P=0.032) and the RFS of patients who got CR1 after one course of induction chemotherapy was significantly longer than that of patients without CR1 [7.6 (2.2-44.1) versus 5.8 (1-19.4), (P=0.048)]. The rate of CR1 in the signal transduction pathway gene mutation group was significantly lower than that in non-mutation group (64.5% vs 100%) (P=0.045), while the level of serum hydroxybutyrate dehydrogenase (HBDH) was significantly higher than that in non-mutation group [(418 (154-2702) vs 246 (110-1068)] (P=0.032). There was no difference in CD56 expression between the two groups (P=0.053), which was limited to the difference between (≥20%) expression and non-expression. (P=0.048). CONCLUSION: CBF-AML patients with signal transduction pathway gene mutation are often accompanied by high HBDH level and CD56 expression, moreover, the remission rate induced by one course of treatment is low.
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Leucemia Mieloide Aguda , Transdução de Sinais , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação , PrognósticoRESUMO
At present, there are no effective methods for the treatment of hemophilia B, and it has high mortality and disability. Therefore, it is very important for the carriers to carry out genetic counseling and make prenatal diagnosis. In this study, we made gene and prenatal diagnoses in a family with a novel F9 gene mutation, and report a novel F9 gene mutation.All exon sequences and flanking sequences of F9 gene were analyzed by Sanger sequencing in the proband; and then according to the F9 gene mutation in the proband, the F9 gene sequencing was performed on the family members. Based on the above results, the pathogenic mutation in F9 gene was finally identified, which was used for prenatal diagnosis.Sanger sequencing revealed c.1232G>C [p.Ser411Thr] mutation in F9 gene in the proband. c.1232G>C heterozygous mutation was also found in the proband's mother and grandmother, but male family members without hemophilia B had no this mutation. The analyses of amniotic fluid samples indicated positive sex-determining region on Y chromosome (SRY), and no c.1232G>C [p.Ser411Thr] mutation in F9 gene.We identified a pathogenic mutation in F9 gene in the family, made a prenatal diagnosis for the female carrier and reported a novel F9 gene mutation.
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Hemofilia B/genética , Diagnóstico Pré-Natal/métodos , Adulto , Éxons , Feminino , Testes Genéticos , Humanos , Masculino , Mutação , GravidezRESUMO
The aim of our study was to evaluate the impact of oral arsenic (the realgar-indigo naturalis formula, RIF) and all-trans retinoic acid (ATRA) on coagulopathy in acute promyelocytic leukemia (APL) compared with intravenous arsenic trioxide (ATO) and ATRA during induction. Mitoxantrone was added to all the patients at a dose of 1.4mg/m2 per day for 5-7 days. D-dimer levels, prothrombin time (PT), fibrinogen (Fbg) levels and the platelet count were comparably analyzed among 83 newly diagnosed APL patients treated with RIF (n=45) or with ATO (n=38). Since induction therapy with RIF and ATRA, the median levels of Fbg, PT and platelets were recovered to the normal range within 4days, 10days and 28days, respectively. The last day of platelet and plasma transfusion was day 12 (range: 0-24 days) and day 3 (range: 0-27 days), respectively. Among the 42 patients with a disseminated intravascular coagulation (DIC) score=4, the consumption of transfused platelets was less in the RIF group than that in the ATO group (P=0.037). In the 17 patients with a DIC score <4, prompt recovery of Fbg levels (P=0.028) was observed in the RIF group compared with that in the ATO group (P=0.401). RIF and ATO showed similar effects on the recovery of coagulopathy in APL patients. RIF had a potential beneficial effect in accelerating the recovery of thrombocytopenia and hypofibrinogenemia for subclinical DIC patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Trióxido de Arsênio/uso terapêutico , Coagulação Intravascular Disseminada/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Leucemia Promielocítica Aguda/complicações , Leucemia Promielocítica Aguda/tratamento farmacológico , Tretinoína/uso terapêutico , Administração Oral , Adolescente , Adulto , Trióxido de Arsênio/administração & dosagem , Transfusão de Sangue , Coagulação Intravascular Disseminada/complicações , Coagulação Intravascular Disseminada/fisiopatologia , Coagulação Intravascular Disseminada/terapia , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Humanos , Leucemia Promielocítica Aguda/sangue , Masculino , Pessoa de Meia-Idade , Mitoxantrona/uso terapêutico , Transfusão de Plaquetas , Estudos Retrospectivos , Tretinoína/administração & dosagem , Adulto JovemRESUMO
The development of acute lymphoblastic leukemia (ALL) from myelodysplastic syndrome (MDS) is a very rare event. The current report presents a rare case of a 33-year-old man who was diagnosed with MDS with multiple-lineage dysplasia (MDS-MLD) that transformed into pro-B-ALL. A missense mutation (S1231F) of the additional sex combs like 1, transcriptional regulator gene was identified, which may have a substantial role in the progression, however does not act as an unfavorable prognostic marker. The patient died during induction chemotherapy. The present study further conducted an analysis on 30 patients to determine progression to ALL. Patients were predominantly male (76.7%, 23/30) with a median age of 56 years (3-90 years). The median time to transformation was 5.5 months (2-50 months). The most common type of MDS with ALL transformation comprised of MDS-excess blasts (MDS-EB; 40%, 12/30), MDS with single-lineage dysplasia (MDS-SLD; 30%, 9/30) and MDS with ring sideroblasts (MDS-RS; 16.7%, 5/30). The majority of the patients transformed to B-cell (66.7%, 16/24) followed by T-cell (33.3%, 8/24) ALL. From the 25 cases where data was available, the complete remission rate was 75% (15/20) with ALL-directed chemotherapy and the median remission duration was 15 months (range 4.5 to 51 months). However, the results indicated that ALL following MDS is characterized by a high rate of early death (20%, 5/25).
RESUMO
The intron 22 inversion is caused by intrachromosomal homologous recombination of the Int22h (intron 22 homologous region) repeats in opposite orientation, accounting for almost 45%-50% of all cases of severe hemophilia A. By contrast, recombinations between similarly oriented int22h repeats in the same chromosome, homologous chromosomes or chromatids may cause deletion or duplication of the intermediate region between the two int22h copies, resulting in false-positive or false-negative possibility that obscure the characterization of intron 22 inversion. The modified long distance PCR(LD-PCR) and inverse shifting PCR(IS-PCR) would distinguish all the possible int22h-mediated rearrangements.
Assuntos
Fator VIII/genética , Hemofilia A/genética , Reação em Cadeia da Polimerase/métodos , Genótipo , Humanos , Íntrons , Recombinação GenéticaRESUMO
In the present case study, a 42-year-old Chinese woman fulfilling the WHO criteria for idiopathic hypereosinophilic syndrome (IHES) who exhibited clinical manifestations of eosinophilic infiltration of multiple tissues including the lungs, heart, central and peripheral nervous system, gastrointestinal tract, spleen, liver and unexplained clinical findings is described. Laboratory investigations revealed the topmost white blood cell and eosinophil that were 150 × 10(9)/L and 136 × 10(9)/L (90.6 %), respectively. To our knowledge, such a large number of eosinophils has rarely been reported, and all reactive causes of hypereosinophilia were excluded. Treatment with cytotoxic chemotherapy, prednisone and dexamethasone was not beneficial. The patient showed a remarkable hematological response when methylprednisolone pulse therapy was initiated when progression of respiratory symptoms occurred, but without clinical remission. The patient subsequently died. We consider that her critical organ damage and poor prognosis were related to the large number of eosinophils and delayed effective anti-eosinophilic therapy after severe organ damage occurred. This case highlights the clinical importance of methylprednisolone pulse therapy which should be initiated without delay once the diagnosis of IHES is made.