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The clinical data of two children with Imerslund-Gräsbeck syndrome (IGS) who were admitted to the First Affiliated Hospital of Zhengzhou University in August 2019 was analyzed retrospectively. The two cases were siblings, aged 8 years and 8 months and 6 years and 2 months, respectively. These two boys had megaloblastic anemia, low level of vitamin B12, hyperhomocysteinemia, accompanied by proteinuria and renal tubular injury, while they showed normal folate level and renal function. Blood tandem mass spectrometry and urine organic acid analysis suggested methylmalonic acidemia (MMA). The initial diagnosis was MMA with homocysteinemia. No known pathogenic gene mutation related to MMA was found by gene sequencing. Compound heterozygous variants of amnionless (AMN) gene were detected: c.43+5G>A and c.C717G. The corrected diagnosis was IGS. Both brothers were treated with long-term intramuscular injection of vitamin B12. After follow-up for one year, these two cases had no clinical symptoms, and their blood indicators remained normal, but proteinuria and renal tubular injury persisted. Blood tandem mass spectrometry and urine organic acid analysis alone may easily lead to misdiagnosis, but combined with genetic testing can improve the accuracy of diagnosis of IGS. Lifelong parenteral vitamin B12 replacement therapy can effectively reverse the clinical and biochemical results, but is uncertain in alleviating albuminuria and renal tubule injury. It's necessary to monitor the renal function regularly.
Assuntos
Anemia Megaloblástica , Deficiência de Vitamina B 12 , Anemia Megaloblástica/genética , Criança , Humanos , Síndromes de Malabsorção , Masculino , Proteinúria , Estudos Retrospectivos , Irmãos , Vitamina B 12RESUMO
To study the curative effects and safety for patients who adopt both gefitinib and platinum-based chemotherapy or only platinum-based chemotherapy in the treatment of lung adenocarcinoma, 80 EGFR mutation-positive lung adenocarcinoma patients in stage IIIB/IV were divided into two groups. Half of them received both gefitinib and standard chemotherapy (group A), and the others (group B) received only standard chemotherapy. Overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and the related toxicities of both groups were recorded in order to take certain nursing measures for a variety of toxicities. Next, statistical methods were used to analyze the curative effects and safety of the two treatments. The results showed that ORR, DCR and median progression-free (mPFS) survival of the two groups of patients showed no statistical difference (P >0.05). However, group A (18.56 months) had a longer median overall survival (mOS) than group B (14.87 months), which was of statistical significance (P less than 0.05). Nausea and loss of appetite were common mild adverse reactions, and anemia and leukocytopenia were moderate common adverse reactions. The difference between these two groups of patients regarding adverse reactions was not statistically significant (P>0.05). In conclusion, the two treatments have similar safety, but lung adenocarcinoma patients with drug resistance during stage IIIB/IV after using first-line gefitinib therapy have lower survival benefits than patients who take both gefitinib and platinum-based chemotherapy.
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Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Cisplatino/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Quinazolinas/administração & dosagem , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Adulto , Idoso , Cisplatino/efeitos adversos , Intervalo Livre de Doença , Feminino , Gefitinibe , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Quinazolinas/efeitos adversos , Taxa de SobrevidaRESUMO
UNLABELLED: Microalgae are a sustainable bioresource, and the biofuel they produce is widely considered to be an alternative to limited natural fuel resources. However, microalgae harvesting is a bottleneck in the development of technology. Axenic Chlorella vulgaris microalgae exhibit poor harvesting, as expressed by a flocculation efficiency of 0·2%. This work optimized the co-culture conditions of C. vulgaris and bioflocculant-producing bacteria in synthetic wastewater using response surface methodology (RSM), thus aiming to enhance C. vulgaris harvesting and lipid content. Three significant process variables- inoculation ratio of bacteria and microalgae, initial glucose concentration, and co-culture time- were proposed in the RSM model. F-values (3·98/8·46) and R(2) values (0·7817/0·8711) both indicated a reasonable prediction by the RSM model. The results showed that C. vulgaris harvesting efficiency reached 45·0-50·0%, and the lipid content was over 21·0% when co-cultured with bioflocculant-producing bacteria under the optimized culture conditions of inoculation ratio of bacteria and microalgae of 0·20-0·25, initial glucose concentration of <1·5 kg m(-3) and co-culture time of 9-14 days. This work provided new insights into microalgae harvesting and cost-effective microalgal bioproducts, and confirmed the promising prospect of introducing bioflocculant-producing bacteria into microalgae bioenergy production. SIGNIFICANCE AND IMPACT OF THE STUDY: This work optimized the co-culture conditions of microalgae (C. vulgaris) and bioflocculant-producing bacteria (F2, Rhizobium radiobacter) in synthetic wastewater using response surface methodology, aiming to enhance C. vulgaris harvesting and lipid produced content. Bioflocculant-producing microbes are environmentally friendly functional materials. They avoid the negative effects of traditional chemical flocculants. This work provided new insights into microalgae harvesting and cost-effective production of microalgal bioproducts, and confirmed the promising prospect of introducing bioflocculant-producing bacteria into microalgae bioenergy production.
Assuntos
Agrobacterium tumefaciens/metabolismo , Chlorella vulgaris/metabolismo , Microalgas/crescimento & desenvolvimento , Microalgas/metabolismo , Águas Residuárias/microbiologia , Agrobacterium tumefaciens/crescimento & desenvolvimento , Biocombustíveis , Chlorella vulgaris/crescimento & desenvolvimento , Técnicas de Cocultura , Metabolismo Energético/fisiologia , Floculação , Lipídeos/biossínteseRESUMO
We investigated the effect of neural stem cells (NSC) and erythropoietin (EPO) on axon regeneration in adult rats with transected spinal cord injury, and provided an experimental basis for clinical treatment. Forty Wistar rats with T10-transected spinal cord injury were randomly divided into four groups of ten rats: a control group (group A), an NSC-transplant group (group B), an NSC-transplant and EPO group (group C), and an EPO group (group D). Biotinylated dextran amines (BDA) anterograde corticospinal cord neuronal tracing and Fluoro-Gold (FG) retrograde tracing were carried out at the 8th week after operation to observe the regeneration of nerve fibers. The Basso, Beattie, and Bresnahan (BBB) locomotor score was used to evaluate restoration. 1) BDA and FG immunofluorescence staining: in group C, a large number of regenerated axons were observed and some penetrated the injured area. In group B, only a small number of regenerated axons were observed and none penetrated the injured area. In group D, only sporadic regenerated nerve fibers were observed occasionally, while in group A, no axonal regeneration was observed. In group C, a small number of cones and axons emitted yellow fluorescence, and no FG-labeled cells were observed in the other groups. 2) The BBB scores for group C were higher than those for the other groups, and the differences were statistically significance (P < 0.05). NSC transplantation combined with EPO intraperitoneal injection may benefit axon regeneration in rats with transected spinal cord injury, and accelerate the functional recovery of the hindlimb locomotor.
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Eritropoetina/administração & dosagem , Regeneração Nervosa/fisiologia , Células-Tronco Neurais/transplante , Traumatismos da Medula Espinal/terapia , Animais , Axônios/fisiologia , Humanos , Ratos , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal/fisiopatologiaRESUMO
Testis-specific serine kinases (TSSKs) are a family of serine/threonine kinases highly expressed in the testes that are responsible for regulating many spermatogenesis-related protein activities. Mutations in this family have a positive relationship with oligospermia and azoospermia in human and mouse. Here, five members of the TSSK family from a Banna mini-pig inbred line (BMI) were cloned, sequenced, and characterized. The full-length coding sequences of BMI TSSKs varied from 807 (TSSK3) to 1095 bp (TSSK1) and encoded 268 to 364 amino acids with molecular weights in the range 30.11 to 41.34 kDa. Following comparison with TSSK4 genes in other species, BMI TSSK4 was found to contain three alternatively spliced variants, inform1, inform 3, and inform 4. BMI TSSK1 and TSSK2 are co-localized on the Sus scrofa chromosome (SSC) 14, and consist of a single exon; TSSK3, TSSK4, and TSSK6 are on SSC6, SSC7, and SSC2, and consist of two, four, and one exon, respectively. Multiple protein sequence alignment and phylogenetic analysis showed that the regions spanning the S_TKc domains were more conserved between pig and other animals: with TSSK1 and TSSK2 and TSSK3 and TSSK6 displaying the greatest degree of homology across species, and the TSSK4 protein clearly distinct from other members. Multi-tissue RT-PCR showed BMI TSSK1, TSSK3, and TSSK4 were only expressed in the testes and seminal vesicle, TSSK2 was confined to testes only, while TSSK6 was expressed widely in adult tissues but was highest in the testes.
Assuntos
Família Multigênica/genética , Proteínas Serina-Treonina Quinases/genética , Espermatogênese/genética , Testículo/crescimento & desenvolvimento , Adulto , Sequência de Aminoácidos/genética , Animais , Clonagem Molecular , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Masculino , Camundongos , Especificidade de Órgãos/genética , Filogenia , Proteínas Serina-Treonina Quinases/biossíntese , Glândulas Seminais/crescimento & desenvolvimento , Glândulas Seminais/metabolismo , Suínos , Porco Miniatura , Testículo/metabolismoRESUMO
Yunnan is situated in the Southwest China and encompasses regions having high biodiversity, including habitats for several ancestral species of domestic animals such as chicken. Domestic chickens in Yunnan were kept by peoples of varied ethnic and economic backgrounds living in highly varied geographic environments. To identify the genetic background of Yunnan domestic chickens and their relationships with Red Junglefowl, we applied 28 widely used microsatellite DNA markers to genotype 340 birds from 7 chicken breeds and Red Junglefowl indigenous to Yunnan. Among a total of 342 alleles identified, 121 (35.4%) were breed specific, with Red Junglefowl harboring most microsatellite alleles (23). High levels of heterozygosity were observed within populations indicated by a mean unbiased HE value of 0.663, which was higher than the reported for most populations elsewhere. The FIS value of domestic populations ranged from -0.098-0.005, indicating a lack of inbreeding among these populations. A high proportion of significant departures (89) from the 224 HWE tests for each locus in each population reflected an excess of heterozygosity and population substructure. Individual assignment tests, high FST values (0.1757-0.3015), and Nei's DA genetic distances (0.4232-0.6950) indicated clear differentiation among these populations. These observations, along with the close genetic distance between indigenous domestic populations and Red Junglefowl, were consistent with the primitive and ancestral state of Yunnan indigenous chickens. Protecting the unique variants of these indigenous poultry varieties from contamination with commercial breeds might provide values for improving modern agricultural livestock and breeding programs. Thus, the current study may benefit breeding management and conservation efforts.
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Cruzamento , Galinhas/genética , Variação Genética , Repetições de Microssatélites/genética , Alelos , Animais , China , Carne , Filogenia , Polimorfismo GenéticoRESUMO
The lymphotoxin beta receptor (LTßR) is a member of the tumor necrosis factor family of receptors (TNFR). It plays a role in regulating lymphoid organogenesis and homeostasis of the immune system. In the present study, the full coding region of a putative LTßR gene of Sus scrofa was amplified by reverse transcription-polymerase chain reaction (RT-PCR) and cloned for the first time (accession Nos. JX457347 and AFU74012). In addition, analysis of the tissue expression profile was carried out via RT-PCR. The full-length coding region of porcine LTßR had 1266 nucleotides (molecular weight, 45.61 kDa; pI, 5.71) and encoded 421 amino acids. Bioinformatic prediction indicates that LTßR belongs to the TNFR superfamily and contains a TNFR domain. The sequence homology analysis revealed that the amino acid sequences of S. scrofa LTßR had 82.9, 82.4, 81.3, 80.5, 78.7, 74.6, and 73.0% identity with those of Equus caballus, Canis lupus, Ailuropoda melanoleuca, Oryctolagus cuniculus, Bos taurus, Mus musculus, and Homo sapiens, respectively. The phylogenetic tree based on the amino acid sequences of LTßR from 8 species revealed that S. scrofa was more closely related to E. caballus, C. lupus, and A. melanoleuca. RT-PCR analysis showed that the porcine LTßR gene was differentially expressed (e.g., high, moderate, low, or nonexistent) in various tissues (e.g., prostate, pituitary, brainstem, and esophagus, respectively). This may be related to differences in the regulation of LTßR in the different tissues.
Assuntos
Clonagem Molecular , Receptor beta de Linfotoxina/química , Fases de Leitura Aberta , Suínos/genética , Sequência de Aminoácidos , Animais , Tronco Encefálico/metabolismo , Bovinos , Cães , Esôfago/metabolismo , Cavalos , Humanos , Ponto Isoelétrico , Receptor beta de Linfotoxina/genética , Receptor beta de Linfotoxina/metabolismo , Masculino , Camundongos , Dados de Sequência Molecular , Peso Molecular , Especificidade de Órgãos , Hipófise/metabolismo , Próstata/metabolismo , Estrutura Terciária de Proteína , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência de Aminoácidos , Suínos/metabolismo , UrsidaeRESUMO
OBJECTIVE: This study aimed to systematically evaluate the effect of whole-body vibration (WBV) training on the improvement of limb function in patients with Parkinson's disease (PD). MATERIALS AND METHODS: An electronic search was performed on the databases, including PubMed, Web of Science, Scopus, SCI-hub, ScienceDirect, Embase, IEEE, Medline, Wiley, ClinicaIKey, CNKI, Wanfang, VIP database, Chinese Medical Association, and CBM Database from inception to May 2022 to collect randomized controlled studies on whole-body vibration training for patients with Parkinson's disease. Two researchers independently screened the literature, extracted the data, and evaluated the quality of the literature, then used ReviewManager 5.4 software for quantitative statistical analysis, including heterogeneity test, sensitivity analysis, risk of bias assessment, combined outcome index effect size and effect size inspection. RESULTS: A total of 9 studies were included in the meta-analysis, including 346 patients, 174 patients in the control group and 172 patients in the observation group. Meta-analysis results showed that, compared with conventional physical therapy or drug therapy alone, whole-body vibration reduced the Unified Parkinson's Disease Rating Scale (UPDRSIII) score and significantly improved the motor function of patients with Parkinson's disease [MD=-2.39, 95% CI (-4.41, -0.37), Z=2.14 (p=0.23)]. Moreover, whole-body vibration significantly improved the walking stability of Parkinson's patients [MD=-1.96, 95% CI (-2.71-1.21), Z=1.17 (p=0.03)]. However, its improvement in balance ability [MD=-0.06, 95% CI (-0.77, 0.65), Z=1.07 (p=0.19)] and daily living ability [MD=0.03, 95% CI (-1.68, 0.74), Z=0.24 (p=0.87)] of patients, it was not t statistically significant. CONCLUSIONS: Compared with conventional therapy, WBV has certain advantages in improving the balance function and gait performance of PD patients, but the effect on balance ability and daily living ability is not significant. Thus, more high-quality research is required for further verification.
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Doença de Parkinson , Vibração , Humanos , Marcha , Doença de Parkinson/terapia , Vibração/uso terapêuticoRESUMO
Objective: To investigate the efficacy of the first-day suspension method for improving the success rate of construction of nasopharyngeal carcinoma-patient derived organoids (NPC-PDO). Methods: The tumor samples of 14 nasopharyngeal carcinoma(NPC) patients, i.e.,13 males and 1 female, with a mean age of 43.0±12.0 years old, were collected from the Affiliated Tumor Hospital of Guangxi Medical University and the First Affiliated Hospital of Guangxi Medical University from January 2022 to July 2022. The tumor samples of 3 patients were digested into single cell suspension and divided into 2 groups, for comparing the efficacy of NPC-PDO construction by the direct inoculation method and the first-day suspension method. The remaining 11 patients were randomized to receive either the direct inoculation method or the first-day suspension method for NPC-PDO construction. The diameter and the number of spheres of NPC-PDO constructed by the two methods were compared by optical microscope; the 3D cell viability detection kit was used to compare the cell viability; the survival rates were compared by trypan blue staining; the success rates of the two construction methods were compared; the number of cases which could be successfully passaged for more than 5 generations and were consistent with the original tissue by pathological examination was counted; and the dynamic changes of cells in suspension overnight were observed by live cell workstation. The independent sample t-test was applied to compare the measurement data of the two groups, and the chi-square test was used to compare the classification data. Results: Compared with the direct inoculation, the diameter and the number of spheres of NPC-PDO constructed by the first-day suspension method were increased, with a higher cell activity, and the success rate of construction was obviously improved (80.0% vs 16.7%, χ2=4.41, P<0.05). In the suspension state, some of the cells aggregated and increased their ability to proliferate. Conclusion: The first-day suspension method can improve the success rate of NPC-PDO construction, especially for those whose original tumor sample size is small.
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Microscopia , Neoplasias Nasofaríngeas , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , China , OrganoidesRESUMO
INTRODUCTION: Three percent sodium chloride (NaCl) treatment has been shown to reduce brain edema and inhibited brain aquaporin 4 (AQP4) expression in bacterial meningitis induced by Escherichia coli. Lipopolysaccharide (LPS) is the main pathogenic component of E. coli. We aimed to explore the effect of 3% NaCl in mouse brain edema induced by LPS, as well as to elucidate the potential mechanisms of action. METHODS: Three percent NaCl was used to treat cerebral edema induced by LPS in mice in vivo. Brain water content, IL-1ß, TNFα, immunoglobulin G (IgG), AQP4 mRNA and protein were measured in brain tissues. IL-1ß, 3% NaCl and calphostin C (a specific inhibitor of protein kinase C) were used to treat the primary astrocytes in vitro. AQP4 mRNA and protein were measured in astrocytes. Differences in various groups were determined by one-way analysis of variance. RESULTS: Three percent NaCl attenuated the increase of brain water content, IL-1ß, TNFα, IgG, AQP4 mRNA and protein in brain tissues induced by LPS. Three percent NaCl inhibited the increase of AQP4 mRNA and protein in astrocytes induced by IL-1ß in vitro. Calphostin C blocked the decrease of AQP4 mRNA and protein in astrocytes induced by 3% NaCl in vitro. CONCLUSIONS: Osmotherapy with 3% NaCl ameliorated LPS-induced cerebral edema in vivo. In addition to its osmotic force, 3% NaCl exerted anti-edema effects possibly through down-regulating the expression of proinflammatory cytokines (IL-1ß and TNFα) and inhibiting the expression of AQP4 induced by proinflammatory cytokines. Three percent NaCl attenuated the expression of AQP4 through activation of protein kinase C in astrocytes.
Assuntos
Aquaporina 4/antagonistas & inibidores , Aquaporina 4/biossíntese , Edema Encefálico/metabolismo , Edema Encefálico/prevenção & controle , Lipopolissacarídeos/toxicidade , Solução Salina Hipertônica/uso terapêutico , Animais , Edema Encefálico/induzido quimicamente , Regulação da Expressão Gênica , Camundongos , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Solução Salina Hipertônica/farmacologiaRESUMO
Schizandrin is recognized as the major absorbed effective constituent of Fructus schisandrae, which is extensively applied in Chinese medicinal formula. The present study aimed to profile the phase I metabolites of schizandrin and identify the cytochrome P450 (CYP) isoforms involved. After schizandrin was incubated with human liver microsomes, three metabolites were isolated by high-performance liquid chromatography (HPLC) and their structures were identified to be 8(R)-hydroxyl-schizandrin, 2-demethyl-8(R)-hydroxyl-schizandrin, 3-demethyl-8(R)-hydroxyl-schizandrin, by liquid chromatography-mass spectrometry (LC-MS), (1)H-nuclear magnetic resonance (NMR), and (13)C-NMR, respectively. A combination of correlation analysis, chemical inhibition studies, assays with recombinant CYPs, and enzyme kinetics indicated that CYP3A4 was the main hepatic isoform that cleared schizandrin. Rat and minipig liver microsomes were included when evaluating species differences, and the results showed little difference among the species. In conclusion, CYP3A4 plays a major role in the biotransformation of schizandrin in human liver microsomes. Minipig and rat could be surrogate models for man in schizandrin pharmacokinetic studies. Better knowledge of schizandrin's metabolic pathway could provide the vital information for understanding the pharmacokinetic behaviours of schizandrin contained in Chinese medicinal formula.
Assuntos
Ciclo-Octanos/farmacocinética , Citocromo P-450 CYP3A/metabolismo , Lignanas/farmacocinética , Redes e Vias Metabólicas , Microssomos Hepáticos/enzimologia , Compostos Policíclicos/farmacocinética , Animais , Catálise/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Ciclo-Octanos/química , Inibidores do Citocromo P-450 CYP3A , Humanos , Cetoconazol/farmacologia , Lignanas/química , Espectrometria de Massas , Microssomos Hepáticos/efeitos dos fármacos , Compostos Policíclicos/química , Ratos , Suínos , Porco Miniatura , Troleandomicina/farmacologiaRESUMO
The SnO2 thin film CO gas sensors have been fabricated on silicon nanostructured surface made using a femtosecond pulsed laser irradiation. The measurement shows a significant response to the CO gas at room temperature. While a SnO2 sensor fabricated on a flat surface shows no response when CO gas exists at room temperature. The high area/volume ratio and sharp structures of the nanospikes enhance the sensitivity of SnO2 at room temperature.
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OBJECTIVE: To discover the effect and mechanism of exogenous microRNA-29b (miR-29b) on proliferation, apoptosis and the sensitivity to chemotherapy of osteosarcoma (OS) cells. PATIENTS AND METHODS: We assessed the expression of microRNA-29b in osteosarcoma tissues evaluating the regulation of in on the OS cell growth and drug sensitivity in human osteosarcoma MG-63 cell model. Firstly, quantitative RT-PCR (reverse transcription-PCR, RT-PCR) was used to measure the expression of miR-29b and matrix metallopeptidase 9(MMP-9) in primary osteosarcoma samples, and to evaluate the correlation between the two molecules. Secondly, miR-29b mimics or mimics were used to modify its expression in MG-63 cells. Luciferase reporter assay, Western blotting, cell viability, colony forming assay and apoptosis examination were performed to assess the regulation by manipulated miR-29b in the osteosarcoma-derived cells. RESULTS: We found that miR-29b is down-expressed, whereas the MMP-9 level was markedly higher in primary osteosarcoma tissues and osteosarcoma-derived cells. We also found that exogenous miR-29b reduces the proliferation, promotes the apoptosis and upregulates the sensitivity to chemotherapy (doxorubicin) of osteosarcoma cells via direct targeting of the MMP-9. CONCLUSIONS: Our data suggest that the reduced miRNA-29b may serve as a predictor of response to chemotherapy and as a therapeutic target in human osteosarcomas.
Assuntos
Neoplasias Ósseas/patologia , Metaloproteinase 9 da Matriz/metabolismo , MicroRNAs/metabolismo , Osteossarcoma/patologia , Regiões 5' não Traduzidas , Adulto , Antagomirs/metabolismo , Antibióticos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Sequência de Bases , Neoplasias Ósseas/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Doxorrubicina/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Metaloproteinase 9 da Matriz/química , Metaloproteinase 9 da Matriz/genética , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Osteossarcoma/genética , Alinhamento de Sequência , Adulto JovemRESUMO
Triptolide, the primary active component of a traditional Chinese medicine Tripterygium wilfordii Hook F, has a wide range of pharmacological activities. In the present study, the metabolism of triptolide by cytochrome P450s was investigated in human and rat liver microsomes. Triptolide was converted to four metabolites (M-1, M-2, M-3, and M-4) in rat liver microsomes and three (M-2, M-3, and M-4) in human liver microsomes. All the products were identified as mono-hydroxylated triptolides by liquid chromatography-mass spectrometry (LC-MS). The studies with chemical selective inhibitors, complementary DNA-expressed human cytochrome P450s, correlation analysis, and enzyme kinetics were also conducted. The results demonstrate that CYP3A4 and CYP2C19 could be involved in the metabolism of triptolide in human liver, and that CYP3A4 was the primary isoform responsible for its hydroxylation.
Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Diterpenos/metabolismo , Microssomos Hepáticos/enzimologia , Fenantrenos/metabolismo , Animais , Cromatografia Líquida , Inibidores das Enzimas do Citocromo P-450 , DNA Complementar/genética , DNA Complementar/metabolismo , Inibidores Enzimáticos/farmacologia , Compostos de Epóxi/metabolismo , Humanos , Hidroxilação , Cinética , Espectrometria de Massas , Microssomos Hepáticos/metabolismo , RatosRESUMO
Objective: To investigate the etiology, clinical and pathological characteristics of laryngeal leukoplakia and the predictive risk factors of recurrence and malignant transformation. Methods: Clinical data of 263 patients with laryngeal leukoplakia between January 2000 and December 2015 were analyzed retrospectively. Results: The pathological diagnoses included squamous epithelial hyperplasia (54.4%), mild dysplasia (17.9%), moderate dysplasia (12.2%), severe dysplasia and carcinoma in situ (12.5%), and invasive carcinoma (3.0%). Age and the extent of lesion were statistically different among different pathological groups (P<0.05). Gender, smoking and alcohol consumption did not show statistical differences among different pathological groups (P>0.05). Follow-up of 215 patients, excluding 6 cases of invasive carcinoma. The recurrence rate was 20.6%(43/209), and the malignant transformation rate was 5.3%(11/209). Multivariate analysis showed that pathological classification of moderate to severe dysplasia was the independent risk factor for recurrence and malignant transformation of laryngeal leukoplakia (P<0.05). In patients with severe dysplasia and carcinoma in situ, the recurrence proportion of conservative treatment, vocal cords (partial) resection and radiotherapy were 8/10, 0/10 and 2/11 respectively. Conclusions: Laryngeal leukoplakia occurs frequently in elderly men with long-term smoking history. Pathological diagnoses are different. The grade of dysplasia is the predictive risk factor for the recurrence and malignant transformation of laryngeal leukoplakia. More aggressive treatment and closer follow-up should be warranted for patients with moderate dysplasia, severe dysplasia and carcinoma in situ.
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Carcinoma in Situ/patologia , Doenças da Laringe/patologia , Leucoplasia/patologia , Consumo de Bebidas Alcoólicas/efeitos adversos , Carcinoma/etiologia , Carcinoma/patologia , Carcinoma/terapia , Carcinoma in Situ/etiologia , Carcinoma in Situ/terapia , Transformação Celular Neoplásica/patologia , Feminino , Humanos , Hiperplasia/patologia , Hiperplasia/terapia , Doenças da Laringe/etiologia , Doenças da Laringe/terapia , Neoplasias Laríngeas/etiologia , Neoplasias Laríngeas/patologia , Leucoplasia/etiologia , Leucoplasia/terapia , Masculino , Recidiva Local de Neoplasia , Recidiva , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Fumar/efeitos adversos , Prega Vocal/cirurgiaRESUMO
Objective: To explore the feasibility and effectiveness of transoral surgery (TOS) for the treatment of hypopharyngeal carcinoma by means of the radiofrequency coblation(RFC). Methods: Twenty-two patients with hypopharyngeal carcinoma who were treated with TOS using RFC during the years of 2010-2016 were enrolled. Among these patients, 15 suffered from pyriform sinus carcinoma, 4 suffered from postcricoid carcinoma, and 3 suffered from posterior hypopharyngeal wall carcinoma. According to the AJCC 2002 guideline, the tumor stages were T1N0M0 for 3 patients, T2N0M0 for 9 patients, T1N1M0 for 1 patient, T1N2M0 for 1 patient, T2N1M0 for 4 patients, and T2N2M0 for 4 patients respectively. All patients with N+ underwent concurrent neck dissection; 2 patients underwent concurrent prophylactic tracheotomy; 17 underwent post-operative radiotherapy for 50-66 Gy. The follow-up time was 6-72 months with a median 35 months.Two patients were lost to follow-up. Results: All patients except 2 underwent the TOS successfully, while the two patients were treated with open approach surgery due to unsure safe margin. Most patients returned to oral feeding within one week. Among the 18 patients with complete follow up data, 3 had the local recurrence of the tumor (16.7%) and one died due to local recurrence, multiple primary esophageal carcinoma, and distant metastasis 4 years after surgery (5.6%). According to the Kaplan-Meier method, the 5-years local control rate and survival rate were 57.8% and 67.5% respectively. All patients had no disorders in speech, swallowing and respiration during the follow up. Conclusions: The RFC can be applied in TOS for the treatments of hypopharyngeal carcinoma with high cutting efficiency and better control of intraoperative hemorrhage, which is useful in lowering the operation difficulty. The oncologic results are comparable to the open surgery with satisfactory postoperative organ function preservation.
Assuntos
Carcinoma/cirurgia , Ablação por Cateter/métodos , Neoplasias Hipofaríngeas/cirurgia , Seio Piriforme/cirurgia , Carcinoma/mortalidade , Carcinoma/patologia , Carcinoma/radioterapia , Terapia Combinada/métodos , Estudos de Viabilidade , Feminino , Humanos , Neoplasias Hipofaríngeas/mortalidade , Neoplasias Hipofaríngeas/patologia , Neoplasias Hipofaríngeas/radioterapia , Estimativa de Kaplan-Meier , Neoplasias Laríngeas/cirurgia , Perda de Seguimento , Masculino , Esvaziamento Cervical , Seio Piriforme/patologia , Taxa de Sobrevida , TraqueotomiaRESUMO
Objective: To introduce the method of transoral coblation-assisted endoscopic minimally invasive surgery for superficial tongue base tumour. Methods: A total of 15 patients treated with transoral coblation-assisted endoscopic minimally invasive surgery from Mar. 2006 to Aug. 2016 were retrospectively reviewed. There were 9 patients with malignant tumors, 6 patients with benign neoplasms. Adjuvant postoperative radiation therapy was applied in three cases of squamous cell carcinoma, neck was performed in four cases of cancer. One case of non-Hodgkin lymphoma received postoperative chemotherapy. Results: One case with ectopic thyroid gland was treated by subtotal resection and one case with squamous cell carcinoma changed into open surgery because of major lingual artery bleeding. The En bloc resection under edoscope was achieved in 92.86%(13/14)of patients. Fifteen cases of neoplasms were followed-up for 8-50 months(median 20 months), one patient with Cowden syndrome was lost to follow-up because of appendical carcinoid combined pulmonary metastasis, one patient with non-Hodgkin lymphoma died of recurrence in other head neck areas 2 years after chemotherapy. Conclusion: Transoral coblation-assisted endoscopic surgery can successfully treat for the patients with superficial tongue base tumours.
Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Laríngeas/cirurgia , Cirurgia Endoscópica por Orifício Natural/métodos , Neoplasias da Língua/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Feminino , Humanos , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/radioterapia , Perda de Seguimento , Linfoma não Hodgkin/radioterapia , Masculino , Procedimentos Cirúrgicos Minimamente Invasivos , Boca , Recidiva Local de Neoplasia , Radioterapia Adjuvante , Estudos Retrospectivos , Neoplasias da Língua/patologia , Neoplasias da Língua/radioterapiaRESUMO
Schisandrin B is an active monomer of the Chinese magnolia vine (Schisandra chinensis) that can reduce transaminase activity in liver cells, inhibit lipid peroxidation, enhance antioxidant status, has protective effects in the liver and has antitumor effects. The present study investigated the potential protective effects of schisandrin B on the p53 signaling pathway in attenuating the inflammatory response, oxidative stress and apoptosis induced by traumatic spinal cord injury (TSCI) in adult rats. Behavioral examination, inclined plate test and spinal cord water content were used to evaluate the protective effect of schisandrin B in TSCI rats. The expression levels of superoxide dismutase (SOD), malondialdehyde (MDA), nuclear factor (NF)κB subunit p65 and tumor necrosis factor (TNF)α were examined using ELISA kits. Western blot analysis was performed to analyze the protein expression of caspase3 and phosphorylated (p)p53 in TSCI rats. In the present study, schisandrin B improved behavioral examination results and the maximum angle of inclined plate test, and inhibited spinal cord water content in rats with TSCI. Notably, schisandrin B reduced the activation of traumatic injuryassociated pathways, including SOD, MDA, NFκB p65 and TNFα, in TSCI rats. In addition, schisandrin B suppressed the TSCIinduced expression of caspase3 and pp53 in TSCI rats. These results indicated that schisandrin B may attenuate the inflammatory response, oxidative stress and apoptosis in TSCI rats by inhibiting the p53 signaling pathway in adult rats.
Assuntos
Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Lignanas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Compostos Policíclicos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Traumatismos da Medula Espinal/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Anti-Inflamatórios/química , Biomarcadores , Caspase 3/metabolismo , Ciclo-Octanos/química , Ciclo-Octanos/farmacologia , Modelos Animais de Doenças , Lignanas/química , Masculino , NF-kappa B/metabolismo , Compostos Policíclicos/química , Ratos , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/patologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Objective:Pharyngeal stenosis as a postoperative complication following pharyngeal surgery (tonsillectomy/adenoidectomy) with coblation is rare and may be difficult to treat. This report is to explore the causes of pharyngeal stenosis and presents our successful treatment experience. Method:From Jan 2012 to July 2016, 5 children with pharyngeal stenosis (2 nasopharyngeal stenosis and 3 nasopharyngeal stenosis combined with oropharyngeal stenosis) secondary to pharyngeal surgery (tonsillectomy/adenoidectomy) in Peking Union Medical College Hospital were analyzed. Five cases with severe nasopharyngeal stenosis received surgery of scar resection, horizontal-to-vertical pharyngoplasty and local pharyngeal flap rotation; and three of them received free skin transplantation. After stenosis repair surgery, prolonged nasopharyngeal hollow stents were used for more than 6 months. To evaluate the therapeutic effect, pharyngeal cavities and symptoms of difficulty nasal breathing, mouth breathing, difficulty in blowing nose, hyponasal speech, snoring, restless sleep, anosmia, dysphagia were assessed and compared before and after surgery. Result:With 7-46 months follow-up, all symptoms of the 5 cases are ameliorated and the diameters of nasopharyx are more than 1.5 cm. No velopharyngeal insufficiency complication happened. Conclusion:Improper operation with coblation can cause severe pharyngeal stenosis. Flap rotation, horizontal-to-vertical pharyngoplasty and prolonged use nasopharyngeal hollow stents are reliable methods to correct pharyngeal stenosis following children's pharyngeal surgery.
Assuntos
Adenoidectomia/efeitos adversos , Faringe/patologia , Tonsilectomia/efeitos adversos , Criança , Constrição Patológica/cirurgia , Humanos , Insuficiência VelofaríngeaRESUMO
Objective: To explore the safety and validity of endoscopic cricopharyngeal myotomy in patients with cricopharyngeal achalasia. Methods: A total of 19 patients with cricopharyngeal achalasia suffered from sustained dysphagia were enrolled in this study. The patients were divided into transcervical cricopharyngeal myotomy(CPM) group and endoscopic CPM (ECPM) group. Swallowing function and complications were evaluated.SPSS7.0 software was used to analyze the data. Results: The swallowing function improved significantly in seven patients in ECPM group, and 9 patients improved in CPM group.The video fluoroscopic swallowing study(VFSS)-swallowing score, VFSS-aspiration score and drinking test score were (3.1±1.1), (3.4±0.8) and (2.0±0.6)in post-ECPM, (3.4±1.4), (3.0±0.9) and (2.2±0.6)in post-CPM. No statistical difference was found in validity between CPM group and ECPM group(t=-0.435, t=1.086, t=-0.607, P>0.05). No statistical difference was observed on the occurrence of complication between two groups. Only one patient had subcutaneous emphysema after operation in ECPM. Conclusions: New surgical instruments and endoscopic surgical technique were safe and effective for cricopharyngeal achalasia. Because these instruments are cheaper, laryngeal endoscopic cricopharyngeal myotomy is easier to be popularized more easily than microscopic laser assistted CPM.