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1.
Curr Oncol ; 30(2): 2405-2416, 2023 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-36826144

RESUMO

PURPOSE: Pleomorphic xanthoastrocytoma (PXA) is an uncommon astrocytoma that tends to occur in children and young adults and has a relatively favorable prognosis. The 2021 WHO classification of tumors of the central nervous system (CNS WHO), 5th edition, rates PXAs as grade 2 and grade 3. The histological grading was based on mitotic activity (≥2.5 mitoses/mm2). This study specifically evaluates the clinical, morphological, and, especially, the molecular characteristics of grade 2 and 3 PXAs. METHODS: Between 2003 and 2021, we characterized 53 tumors with histologically defined grade 2 PXA (n = 36, 68%) and grade 3 PXA (n = 17, 32%). RESULTS: Compared with grade 2 PXA, grade 3 PXA has a deeper location and no superiority in the temporal lobe and is more likely to be accompanied by peritumoral edema. In histomorphology, epithelioid cells and necrosis were more likely to occur in grade 3 PXA. Molecular analysis found that the TERT promoter mutation was more prevalent in grade 3 PXA than in grade 2 PXA (35% vs. 3%; p = 0.0005) and all mutation sites were C228T. The cases without BRAF V600E mutation or with necrosis in grade 3 PXA had a poor prognosis (p = 0.01). CONCLUSION: These data define PXA as a heterogeneous astrocytoma. Grade 2 and grade 3 PXAs have different clinical and histological characteristics as well as distinct molecular profiles. TERT promoter mutations may be a significant genetic event associated with anaplastic progression. Necrosis and BRAF V600E mutation play an important role in the prognosis of grade 3 PXA.


Assuntos
Astrocitoma , Proteínas Proto-Oncogênicas B-raf , Criança , Adulto Jovem , Humanos , Proteínas Proto-Oncogênicas B-raf/genética , Astrocitoma/genética , Astrocitoma/patologia , Mutação , Prognóstico
2.
J Gene Med ; 25(1): e3461, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36314054

RESUMO

BACKGROUND: Congenital heart disease (CHD) frequently manifests as a complex phenotype and approximately one-third of cases may be caused by genetic factors. BCOR, an X-linked gene encoding the corepressor of BCL6, has been demonstrated to be closely involved in human heart development. However, whether BCOR variants represent the genetic etiology underlying CHD needs further investigation. METHODS: We performed whole exome sequencing on CHD nuclear families and identified a candidate gene, BCOR, by robust bioinformatic analysis and medical literature searches. Targeted DNA sequencing of the candidate gene was conducted and then the association between variants and the risk of developing CHD was analyzed. The effects of BCOR mutations on gene expression, localization, protein interaction, and signaling pathways were evaluated in vitro. RESULTS: We identified a BCOR hemizygous missense variant (c.1448C>T, p.Pro483Leu) in a male proband presented with CHD/heterotaxy. Sanger sequencing confirmed that this variant was inherited from his asymptomatic mother. Interestingly, through literature searches, we observed another novel BCOR hemizygous missense variant (c.1619G>A, p.Arg540Gln) in a CHD patient with heterotaxy, supporting the pathogenic evidence of BCOR variants. Functional experiments conducted in vitro revealed that the variant p.Pro483Leu altered the subcellular localization of BCOR protein, disrupted its interaction with BCL6, and significantly promoted cell proliferation, whereas the variant p.Arg540Gln displayed no obvious effects. Nevertheless, transcriptional analysis revealed that down-regulation of BCOR substantially enhanced the activities of mitogen-activated protein and phosphoinositide 3-kinase-AKT signaling pathways, which are closely attributed to heart development. Targeted sequencing of 932 sporadic CHD patients enriched nine variants of BCOR predicted as likely rare and damaging and a septal defect was present in 81.8% (9/11) of them, including the two probands, which was consistent with the possible phenotype caused by BCOR defects. CONCLUSIONS: The findings of the present study indicate that variants in BCOR may predispose individuals to CHD in the Chinese Han population.


Assuntos
Cardiopatias Congênitas , Defeitos dos Septos Cardíacos , Humanos , Masculino , Genes Ligados ao Cromossomo X , População do Leste Asiático , Fosfatidilinositol 3-Quinases , Cardiopatias Congênitas/genética , Defeitos dos Septos Cardíacos/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Repressoras/genética
3.
Pharmacol Ther ; 232: 108004, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34597754

RESUMO

The liver has the ability to repair itself after injury; however, a variety of pathological changes in the liver can affect its ability to regenerate, and this could lead to liver failure. Mesenchymal stem cells (MSCs) are considered a good source of cells for regenerative medicine, as they regulate liver regeneration through different mechanisms, and their efficacy has been demonstrated by many animal experiments and clinical studies. Induced pluripotent stem cells, another good source of MSCs, have also made great progress in the establishment of organoids, such as liver disease models, and in drug screening. Owing to the recent developments in MSCs and induced pluripotent stem cells, combined with emerging technologies including graphene, nano-biomaterials, and gene editing, precision medicine and individualized clinical treatment may be realized in the near future.


Assuntos
Células-Tronco Pluripotentes Induzidas , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Animais , Humanos , Regeneração Hepática , Medicina Regenerativa
4.
Front Immunol ; 12: 690565, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34054880

RESUMO

Immunotherapy has become an indispensable part of the comprehensive treatment of hepatocellular carcinoma (HCC). Immunotherapy has proven effective in patients with early HCC, advanced HCC, or HCC recurrence after liver transplantation. Clinically, the most commonly used immunotherapy is immune checkpoint inhibition using monoclonal antibodies, such as CTLA-4 and PD-1. However, it cannot fundamentally solve the problems of a weakened immune system and inactivation of immune cells involved in killing tumor cells. T cells can express tumor antigen-recognizing T cell receptors (TCRs) or chimeric antigen receptors (CARs) on the cell surface through gene editing to improve the specificity and responsiveness of immune cells. According to previous studies, TCR-T cell therapy is significantly better than CAR-T cell therapy in the treatment of solid tumors and is one of the most promising immune cell therapies for solid tumors so far. However, its application in the treatment of HCC is still being researched. Technological advancements in induction and redifferentiation of induced pluripotent stem cells (iPSCs) allow us to use T cells to induce T cell-derived iPSCs (T-iPSCs) and then differentiate them into TCR-T cells. This has allowed a convenient strategy to study HCC models and explore optimal treatment strategies. This review gives an overview of the major advances in the development of protocols to generate neoantigen-specific TCR-T cells from T-iPSCs. We will also discuss their potential and challenges in the treatment of HCC.


Assuntos
Antígenos de Neoplasias/imunologia , Carcinoma Hepatocelular/terapia , Imunoterapia Adotiva , Células-Tronco Pluripotentes Induzidas/transplante , Neoplasias Hepáticas/terapia , Linfócitos T/transplante , Animais , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/metabolismo , Diferenciação Celular , Humanos , Células-Tronco Pluripotentes Induzidas/imunologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/metabolismo , Fenótipo , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Resultado do Tratamento
5.
Zhongguo Zhong Yao Za Zhi ; 46(9): 2254-2259, 2021 May.
Artigo em Chinês | MEDLINE | ID: mdl-34047128

RESUMO

Rhus chinensis is an important resource plant. The aqueous extract of R. chinensis roots or stems was to produce Shuguantong Syrup, which is mainly used for the treatment of coronary heart disease and angina pectoris with definite curative effect. On this basis, the crude phenolic part of R. chinensis prepared by macroporous resin was evaluated for the cardio protective effect against myocardial ischemia in mice. The results showed that the phenolic part group with oral administration at the dosages of 190.8-381.6 mg·kg~(-1), compared with the model group, reduced the values of left ventricular end systolic diameter(LVEDs) and the left ventricular end diastolic diameter(LVEDd), and increased the cardiac ejection fraction(EF) and left ventricular fractional shortening(FS) rate, which could effectively improve cardiac function and exert its anti-myocardial ischemia effect, and reduce the rising levels of creatine kinase isoenzyme(CK-MB) and lactate dehydrogenase(LDH) in serum. HE staining showed that the phenolic part group reduced the infiltration of myocardial inflammatory cells and alleviated the degree of myocardial fibrosis and collagen deposition. TUNEL staining showed that the blue-green fluorescence of the phenolic part group decreased successively, and the degree of myocardial cell apoptosis was reduced. Immunohistochemical staining suggested that it could reduce the number of positive cells for p53 protein expression and significantly improve myocardial cell damage. All above data suggested that the phenolic part group had an anti-mycardial ischemis effect. Related mechanism studies revealed that the crude phenolic part could regulate the expressions of the p53 gene(p53), Bcl-2-associated X protein(Bax), B lymphoma-2 gene(Bcl-2), and caspase-3 protein(caspase-3) in myocardial tissue, suggesting that it could reduce cardiac remodeling and myocardial ischemic damage, and improve cardiac function by inhibiting myocardial apoptosis.This research laid a foundation for the elucidation of the pharmacological ingredients R. chinensis.


Assuntos
Isquemia Miocárdica , Extratos Vegetais/farmacologia , Rhus , Animais , Apoptose , Camundongos , Isquemia Miocárdica/tratamento farmacológico , Miocárdio , Miócitos Cardíacos , Proteína X Associada a bcl-2
6.
Zhongguo Zhong Yao Za Zhi ; 45(2): 303-311, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32237312

RESUMO

The Aspongopus chinensis is an insect of the genus Hemiptera, which can be used both as a medicinal and as a gourmet in the folk. It has a long history as a drug, which has the effect of regulating Qi and relieving pain, and warming the Yang. It is mainly used to treat stomach cold and pain, liver and stomach pain, kidney deficiency and impotence, and waist and knee pain. Modern pharmacological studies have shown that A. chinensis has a variety of pharmacological activities. For example, it can be used to fight tumors, improve reproductive damage, and antibacterial, anti-oxidation, anti-coagulation, anti-ulcer, anti-fatigue and so on. The chemical constituents of A. chinensis currently reported mainly include odorous components, vitamins, fatty acids and proteins, amino acids, and other nutrients, as well as nucleosides and dopamines. This study summarizes and analyzes the related research literatures of A. chinensis in China and abroad, and provides a reference for its further development and research from the aspects of chemical composition, pharmacological action and clinical application.


Assuntos
Produtos Biológicos/química , Heterópteros/química , Animais , China , Medicina Tradicional Chinesa
7.
Zhongguo Zhong Yao Za Zhi ; 45(24): 5917-5928, 2020 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-33496131

RESUMO

Saussurea lappa originates in India, and now mainly grow in Yunnan, Sichuan and other places in China. It is one of the commonly used traditional herbal medicines in Tibet and other minority regions, with effects in regulating qi to relieve pain and invigo-rating spleen to promote food. It has been used in clinic for gastrointestinal diseases, such as Qi stagnation syndrome of spleen and stomach, diarrhea and tenesmus. More than 200 compounds have been identified from S. lappa. Among them, sesquiterpenoids attracted much attention. In terms of the number of compounds, eudesmanetype is dominant, guaiane and germacranetypes have also been reported frequently. Pharmacological studies have involved extracts, volatile oils and monomeric components represented by dehydrocostus lactone. Anti-tumor, anti-inflammatory and anti-bacterial effects on digestive system have attracted great attention. However, due to the complex sources of S. lappa and widely used in clinical practice, there is few research progress on relevant chemical constituents and pharmacological activities. This paper systematically summarizes terpenes and the pharmacological effects of S. lappa, in order to provide basis for further studies and clinical applications.


Assuntos
Saussurea , Sesquiterpenos , China , Extratos Vegetais , Terpenos , Tibet
8.
Front Cell Dev Biol ; 8: 622393, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33553159

RESUMO

Acute lymphoblastic leukemia (ALL) as a common cancer is a heterogeneous disease which is mainly divided into BCP-ALL and T-ALL, accounting for 80-85% and 15-20%, respectively. There are many differences between BCP-ALL and T-ALL, including prognosis, treatment, drug screening, gene research and so on. In this study, starting with methylation and gene expression data, we analyzed the molecular differences between BCP-ALL and T-ALL and identified the multi-omics signatures using Boruta and Monte Carlo feature selection methods. There were 7 expression signature genes (CD3D, VPREB3, HLA-DRA, PAX5, BLNK, GALNT6, SLC4A8) and 168 methylation sites corresponding to 175 methylation signature genes. The overall accuracy, accuracy of BCP-ALL, accuracy of T-ALL of the RIPPER (Repeated Incremental Pruning to Produce Error Reduction) classifier using these signatures evaluated with 10-fold cross validation repeated 3 times were 0.973, 0.990, and 0.933, respectively. Two overlapped genes between 175 methylation signature genes and 7 expression signature genes were CD3D and VPREB3. The network analysis of the methylation and expression signature genes suggested that their common gene, CD3D, was not only different on both methylation and expression levels, but also played a key regulatory role as hub on the network. Our results provided insights of understanding the underlying molecular mechanisms of ALL and facilitated more precision diagnosis and treatment of ALL.

9.
Chin Med J (Engl) ; 132(17): 2105-2108, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31348032

RESUMO

OBJECTIVE: In recent years, attempting the biventricular pathway or biventricular conversions in patients with borderline ventricle has become a hot topic. However, inappropriate pursuit of biventricular repair in borderline candidates will lead to adverse clinical outcomes. Therefore, it is important to accurately assess the degree of ventricular development before operation and whether it can tolerate biventricular repair. This review evaluated ventricular development using echocardiography for a better prediction of biventricular repair in borderline ventricle. DATA SOURCES: Articles from January 1, 1990 to April 1, 2019 on biventricular repair in borderline ventricle were accessed from PubMed, using keywords including "borderline ventricle," "congenital heart disease," "CHD," "echocardiography," and "biventricular repair." STUDY SELECTION: Original articles and critical reviews relevant to the review's theme were selected. RESULTS: Borderline left ventricle (LV): (1) Critical aortic stenosis: the Rhodes score, Congenital Heart Surgeons Society regression equation and another new scoring system was proposed to predict the feasibility of biventricular repair. (2) Aortic arch hypoplasia: the LV size and the diameter of aortic and mitral valve (MV) annulus should be taken into considerations for biventricular repair. (3) Right-dominant unbalanced atrioventricular septal defect (AVSD): atrioventricular valve index (AVVI), left ventricular inflow index (LVII), and right ventricle (RV)/LV inflow angle were the echocardiographic indices for biventricular repair. Borderline RV: (1) pulmonary atresia/intact ventricular septum (PA/IVS): the diameter z-score of tricuspid valve (TV) annulus, ratio of TV to MV diameter, RV inlet length z-score, RV area z-score, RV development index, and RV-TV index, etc. Less objective but more practical description is to classify the RV as tripartite, bipartite, and unipartite. The presence or absence of RV sinusoids, RV dependent coronary circulation, and the degree of tricuspid regurgitation should also be noted. (2) Left-dominant unbalanced AVSD: AVVI, LV, and RV volumes, whether apex forming ventricles were the echocardiographic indices for biventricular repair. CONCLUSIONS: Although the evaluation of echocardiography cannot guarantee the success of biventricular repair surgery, echocardiography can still provide relatively valuable basis for surgical decision making.


Assuntos
Ecocardiografia/métodos , Cardiopatias Congênitas/cirurgia , Ventrículos do Coração/cirurgia , Hemodinâmica , Humanos
10.
Clin Cancer Res ; 25(3): 1070-1086, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30397177

RESUMO

PURPOSE: Cancer stem-like cells (CSCs) contribute to bladder cancer chemotherapy resistance and progression, but the associated mechanisms have not been elucidated. This study determined whether blocking an autocrine signaling loop in CSCs improves the therapeutic effects of cis-platinum on bladder cancer. EXPERIMENTAL DESIGN: The expression of the epithelial marker OV6 and other markers in human bladder cancer specimens was examined by IHC. The CSC properties of magnetic-activated cell sorting (MACS)-isolated OV6+ and OV6- bladder cancer cells were examined. Molecular mechanisms were assessed through RNA-Seq, cytokine antibody arrays, co-immunoprecipitation (co-IP), chromatin immunoprecipitation (ChIP) and other assays. An orthotopic bladder cancer mouse model was established to evaluate the in vivo effects of a YAP inhibitor (verteporfin) and a PDGFR inhibitor (CP-673451) on the cis-platinum resistance of OV6+ CSCs in bladder cancer. RESULTS: Upregulated OV6 expression positively associated with disease progression and poor prognosis for bladder cancer patients. Compared with OV6- cells, OV6+ bladder cancer cells exhibited strong CSC characteristics, including self-renewal, tumor initiation in NOD/SCID mice, and chemotherapy resistance. YAP, which maintains the stemness of OV6+ CSCs, triggered PDGFB transcription by recruiting TEAD1. Autocrine PDGF-BB signaling through its receptor PDGFR stabilized YAP and facilitated YAP nuclear translocation. Furthermore, blocking the YAP/TEAD1/PDGF-BB/PDGFR loop with verteporfin or CP-673451 inhibited the cis-platinum resistance of OV6+ bladder cancer CSCs in an orthotopic bladder cancer model. CONCLUSIONS: OV6 could be a helpful indicator of disease progression and prognosis for patients with bladder cancer, and targeting the autocrine YAP/TEAD1/PDGF-BB/PDGFR loop might serve as a remedy for cis-platinum resistance in patients with advanced bladder cancer.


Assuntos
Comunicação Autócrina/genética , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Células-Tronco Neoplásicas/efeitos dos fármacos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Benzimidazóis/farmacologia , Linhagem Celular Tumoral , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos Endogâmicos NOD , Camundongos SCID , Células-Tronco Neoplásicas/metabolismo , Quinolinas/farmacologia , Receptores do Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores , Receptores do Fator de Crescimento Derivado de Plaquetas/metabolismo , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/metabolismo , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Verteporfina/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Proteínas de Sinalização YAP
11.
Appl Biochem Biotechnol ; 181(4): 1372-1387, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27796874

RESUMO

Six characteristic di-acetylated lactonic sophorolipids with C16:1, C16:0, C18:0, C18:1, C18:2, and C18:3 fatty acid were obtained from Starmerella bombicola CGMCC 1576. In order to confirm their anticancer activity against human cervical cancer cells and reveal the structure-activity relationships, their anti-proliferation effects on HeLa and CaSki cells were estimated. The cytotoxicity of sophorolipid molecules with different degrees of unsaturation was proved to be influenced by carbon chain length of sophorolipids. The longer the carbon chain length, the stronger the cytotoxicity of sophorolipids. The inhibitory mechanism of a di-acetylated lactonic C18:1 sophorolipid on HeLa cells was investigated. The cells developed many features of apoptosis and cell cycle was blocked at G0 phase and partly at G2 phase. The expression of CHOP and Bip/GRP78 was induced. Caspase-12 and caspase-3 were both activated. However, mitochondrial membrane potential and concentration of cytosolic cytochrome C did not change. The induced apoptosis of HeLa cells was probably triggered through endoplasmic reticulum signaling pathway without involvement of mitochondria. In vivo, 5, 50, and 500 mg/kg lactonic sophorolipids showed 29.90, 41.24, and 52.06 % of inhibition without significant toxicity to tumor-bearing mice, respectively. Our findings may suggest a potential use of sophorolipids in human cervical cancer treatment.


Assuntos
Antineoplásicos/farmacologia , Glicolipídeos/farmacologia , Neoplasias do Colo do Útero/patologia , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/patologia , Chaperona BiP do Retículo Endoplasmático , Feminino , Glicolipídeos/química , Glicolipídeos/isolamento & purificação , Células HeLa , Humanos , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Saccharomycetales/química , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade , Ensaios Antitumorais Modelo de Xenoenxerto
12.
BMC Med Genet ; 17(1): 87, 2016 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-27876007

RESUMO

BACKGROUND: The purpose of the study was to investigate the effects of the pregnane X receptor (PXR)*1B polymorphisms on CYP3A4 enzyme activity and postoperative fentanyl consumption in Chinese patients undergoing gynecological surgery. METHODS: A total of 287 females of Han ethnicity, aged 20 to 50 years old, ASA I or II, scheduled to abdominal total hysterectomy or myomectomy under general anesthesia were enrolled. The analgesic model used was fentanyl consumption via patient-controlled intravenous analgesia (PCIA) in the post-operative period. Additionally, pain was assessed using a visual analog score (VAS). Pain scores, occurrence of adverse reactions and consumption of fentanyl were recorded during the 24 h postoperative period. The enzyme activity of CYP3A4 was evaluated by measuring the plasma ratio of 1'-hydroxymidazolam to midazolam 1 h after intravenous administration of 0.1 mg/kg midazolam. PXR genotyping was performed by direct DNA sequencing and the PXR * 1B haplotype was analyzed via PHASE V.2.1 software. RESULTS: The polymorphism frequency of PXR11156A > C/11193 T > C and 8055C > T were 49.6 and 49.3%, and the rate of PXR * 1B haplotype was 48.8% in our study. None of the pain scores, consumption of fentanyl 24 h post-operatively or enzyme activity of CYP3A4, showed differences among different genotypes. CONCLUSIONS: PXR11156A > C, PXR11193T > C, PXR8055C > T or the PXR * 1B haplotype do not appear to be important factors contributing to CYP3A4 activity and interindividual variations in postoperative fentanyl consumption in Han female patients undergoing gynecological surgery. TRIAL REGISTRATION: The DNA samples were obtained since 2007 to 2010 year in our hospital, there was no registration at that time. So this section is not applicable to our research.


Assuntos
Povo Asiático/genética , Fentanila/administração & dosagem , Dor Pós-Operatória/prevenção & controle , Receptores de Esteroides/genética , Adulto , Alelos , Analgesia Controlada pelo Paciente , China , Citocromo P-450 CYP3A/metabolismo , DNA/química , DNA/isolamento & purificação , DNA/metabolismo , Análise Mutacional de DNA , Feminino , Frequência do Gene , Genótipo , Procedimentos Cirúrgicos em Ginecologia , Haplótipos , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Receptor de Pregnano X
13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 24(2): 444-7, 2016 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-27151007

RESUMO

OBJECTIVE: To investigate the therapeutic efficacy of rituximab combined with methotrexate on patients with primary central nervous system lymphoma. METHODS: Fifty eight patients with central nervous system lymphoma treated in our hospital from February 2008 to September 2011 years were randomly divided into the observation group and the control group. The control group was treated with methotrexate combined with whole brain radiotherapy; the observation group was treated by rituximab combined with methotrexate. The curative efficacy, adverse effects, life quality, and the 1 and 3 year survival rate after 2 cycles of treatment were compared between 2 groups. RESULTS: The total effective rate of observation group was 82.76%, which significantly higher than 58.62% of the control group (P < 0.05). In observation group, the incidences of anemia, liver damage, gastrointestinal side effect and oral ulcer were significantly lower than that in control group, respectively (P < 0.05). The physiological function, physical function, health status, social and emotional function in the observation group were significantly higher than those in the control group (P < 0.05), 1 and 3 years survival rates in the observation group were 86.21% and 62.07%, significantly higher than 58.62% and 31.03% in the control group (P < 0.05). CONCLUSION: Targeted therapy combined with chemotherapy for the primary central nervous system lymphoma can improve the patients' outcomes, reduce adverse effects, and improve the quality of life and survival rate.


Assuntos
Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Metotrexato/uso terapêutico , Rituximab/uso terapêutico , Humanos , Qualidade de Vida , Taxa de Sobrevida , Resultado do Tratamento
14.
Chronic Dis Transl Med ; 2(1): 55-60, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29063026

RESUMO

OBJECTIVE: Previous studies have revealed inconsistent results regarding the association between occult hepatitis B virus (HBV) infection and chronic kidney disease (CKD). Therefore, we conducted a prospective cohort study to evaluate the association between occult HBV infection and CKD. METHODS: A total of 4329 adults, aged 46.2 ± 13.7 years, without CKD at baseline were enrolled while undergoing physical examinations. Occult HBV infection was defined as seropositivity for antibody to HBV core antigen. CKD was defined as decreased estimated glomerular filtration rate (eGFR < 60 ml·min-1·1.73 m-2) or presence of proteinuria ≥1+, assessed using a repeated dipstick method. eGFR was computed using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. RESULTS: The prevalence of occult HBV infection was 8.1% (352/4329). During 5 years of follow-up, 165 patients (3.8%) developed CKD. Univariate Logistic regression analysis showed that occult HBV infection was positively associated with decreased eGFR, with an odds ratio (OR) of 2.15 (95% confidence interval (CI): 1.05-4.11). In contrast, occult HBV infection was not associated with either proteinuria or CKD (P > 0.05). After adjustment for potential confounders in the multivariate Logistic regression analysis, age, hypertension, diabetes, and the highest quartile of uric acid were associated with CKD, with ORs of 1.04 (95% CI: 1.02-1.05), 2.1 (95% CI: 1.46-3.01), 2.02 (95% CI: 1.36-2.99), and 1.86 (95% CI: 1.17-2.95), respectively. However, occult HBV infection was not associated with CKD, with an OR of 1.12 (95% CI: 0.65-1.95). CONCLUSIONS: This study did not find an association between occult HBV infection and CKD. However, high-risk patients infected with HBV should still be targeted for monitoring for the development of CKD.

15.
Pharmacology ; 96(1-2): 55-60, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26088794

RESUMO

PURPOSE: This study aimed to investigate whether CYP3A4*1G genetic polymorphism influences the metabolism of fentanyl in human liver microsomes in Chinese patients. METHODS: The human liver microsomes were obtained from 88 hepatobiliary surgery patients who accepted liver resection surgery in this study. A normal liver sample (confirmed by the Department of Pathology) was taken from the outer edge of the resected tissue. The metabolism of fentanyl in human liver microsomes was studied. The concentration of fentanyl was measured by high performance liquid chromatography. The CYP3A4*1G variant allele was genotyped using the PCR restriction fragment length polymorphism method. RESULTS: The frequency of the CYP3A4*1G variant allele was 0.188 in the 88 Chinese patients who had received hepatobiliary surgery. The metabolic rate of fentanyl in patients homozygous for the *1G/*1G variant (0.85 ± 0.37) was significantly lower than that in patients bearing the wild-type allele *1/*1 (1.89 ± 0.58) or in patients heterozygous for the *1/*1G variant (1.82 ± 0.65; p < 0.05). There were no gender-related differences in the metabolic rate of fentanyl (p > 0.05) nor was there any correlation between age and metabolic rate of fentanyl (p > 0.05). Results from different hepatobiliary diseases showed no significant difference in the metabolic rate of fentanyl (p > 0.05). The difference of CYP3A4 mRNA among different CYP3A4*1G variant alleles was significant (p < 0.05). There was positive correlation between CYP3A4 mRNA and metabolic rate of fentanyl (p < 0.01). CONCLUSIONS: CYP3A4*1G genetic polymorphism decreases the metabolism of fentanyl. There is a positive correlation between CYP3A4 mRNA level and metabolism of fentanyl.


Assuntos
Povo Asiático/genética , Citocromo P-450 CYP3A/genética , Fentanila/metabolismo , Microssomos Hepáticos/metabolismo , Polimorfismo Genético/genética , Alelos , China , Feminino , Fentanila/farmacocinética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade
16.
Front Biosci (Landmark Ed) ; 20(6): 964-74, 2015 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-25961536

RESUMO

Ventricular septal defect (VSD) is one of the common congenital heart malformations. Several factors lead to the development of VSD, including familial causes, exposure to certain drugs, infectious agents, and maternal metabolic disturbances. We considered that induced pluripotent stem (iPS) cells derived from VSD patients can be used to study the origin and pathogenesis of the VSD. Here, we show generation and cardiomyocyte differentiation potential of iPS cells from thymic epithelial cells of a patient with VSD (TECs-VSD) by overexpressing the four factors: OCT4, SOX2, NANOG, and LIN28 with lentiviral vectors. The self-renewal and pluripotency of the VSD-iPS cells was verified in iPS cells by in vitro expression of pluripotency markers and formation of teratoma in vivo. iPS cell lines from VSD patients differentiated into functional cardiomyocytes can serve as a model system for studying the pathophysiology and identifying etiology of VSD.


Assuntos
Diferenciação Celular , Células-Tronco Pluripotentes Induzidas/citologia , Miócitos Cardíacos/citologia , Animais , Técnicas de Cultura de Células , Linhagem Celular , Comunicação Interventricular/patologia , Humanos , Camundongos Endogâmicos , Timo/citologia
18.
Carbohydr Polym ; 97(2): 690-4, 2013 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-23911502

RESUMO

Phosphorylated polysaccharide PLEP-1a, with the PO4³â» content of 6.39%, was prepared from LEP-1a by phosphorylation. IR, (13)C NMR and (31)P NMR results of PLEP-1a showed that the original basic structure of the polysaccharide was not changed, and the -H2PO3 group was linked at C6 of LEP-1a. The results of anti-tumor experiments in vivo showed that 100 mg/kg and 400 mg/kg of LEP-1a could significantly improve the food consumption, body weight, tumor inhibition rate and thymus index of S180 sarcoma mice, and increase the levels of SOD, IL-2 and TNF-α in mice blood serum, indicating that LEP-1a had an excellent anti-tumor activity. Furthermore, PLEP-1a had a significantly enhanced inhibitory effect on S180 sarcoma mice than LEP-1a, suggesting that phosphorylation is an effective way of improving the biological activity of LEP-1a.


Assuntos
Antineoplásicos/farmacologia , Ascomicetos/química , Polissacarídeos/farmacologia , Animais , Comportamento Alimentar/efeitos dos fármacos , Feminino , Interleucina-2/metabolismo , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Especificidade de Órgãos/efeitos dos fármacos , Fosfatos/análise , Fosforilação/efeitos dos fármacos , Padrões de Referência , Sarcoma 180/enzimologia , Sarcoma 180/patologia , Espectrofotometria Infravermelho , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Aumento de Peso/efeitos dos fármacos
19.
J Huazhong Univ Sci Technolog Med Sci ; 33(3): 447-451, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23771676

RESUMO

The purpose of this study was to evaluate the value of multi-detector computed tomography (MDCT) angiography for the diagnosis of congenital aortic arch anomalies and present the radiological images of congenital aortic arch anomalies in Chinese children. MDCT angiography and transthoracic echocardiography (TTE) were applied for the diagnosis of congenital aortic arch anomalies in 362 Chinese children between May 2006 and December 2011 (age ranges from 5 days to 12 years; mean age, 3.3 years). Surgery and/or catheter angiography (CA) were conducted in all patients to confirm the final diagnosis. In the 362 Chinese children with congenital heart anomalies, congenital aortic arch anomalies were definitely diagnosed in 198 children and 164 children ruled out by operation and/or (CA). Among the 198 children with anomalies, coarctation of aorta (CoA), interruption of aortic arch (IAA), right aortic arch, aberrant right subclavian artery and double aortic arch were diagnosed in 134, 32, 20, 10 and 2 children respectively, and there were 6 cases with uncommon congenital aortic arch anomalies: 2 had double aortic arch including 1 with five branches of the aortic arch, 2 had isolation of the right subclavian artery with two patent ductus arteriosus (PDA), 1 had an isolation of the common carotid artery with a PDA, and 1 had double PDA with a single ventricle and pulmonary artery atresia. Among the 32 children with IAA, 28 were of type A, and 4 were of type B. The diagnostic sensitivity, specificity and accuracy of MDCT angiography for congenital aortic arch anomalies were 100% (198/198), 98% (161/164) and 99% (359/362), respectively. The diagnostic sensitivity, specificity and accuracy of TTE were 92% (182/198), 81% (133/164) and 87% (315/362), respectively. In conclusion, MDCT angiography is a reliable, noninvasive imaging technique for the diagnosis of congenital aortic arch anomalies in children. Sometimes, even more information can be obtained from this technique than from conventional angiography.


Assuntos
Anormalidades Múltiplas/diagnóstico por imagem , Aorta Torácica/anormalidades , Aorta Torácica/diagnóstico por imagem , Síndromes do Arco Aórtico/diagnóstico por imagem , Aortografia/métodos , Tomografia Computadorizada Multidetectores/métodos , Tomografia Computadorizada por Raios X/métodos , Criança , Pré-Escolar , China , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
20.
Biotechnol Lett ; 35(6): 901-8, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23386226

RESUMO

Sophorolipids (SLs) were synthesized by Wickerhamiella domercqiae var. sophorolipid CGMCC 1576 grown on fish oil and glucose. They were purified using preparative HPLC and their structures were identified by MS/MS. The yields of total and lactonic SLs were 47 and 19 g l(-1) in shake-flasks when fish oil 4 % (v/v) was used with glucose in the medium. The composition of SL mixture contained more than 20 SL molecules. Several unconventional SL molecules with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) including zero-, mono- and di-acetylated acidic SLs with EPA and a di-acetylated acidic SL with DHA were obtained. Two unconventional lactonic SL molecules, non-acetylated lactonic SL with 22:3 and non-acetylated lactonic SL with 20:0, were also obtained.


Assuntos
Carbono/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Ácido Eicosapentaenoico/metabolismo , Óleos de Peixe/metabolismo , Glicolipídeos/metabolismo , Saccharomycetales/metabolismo , Cromatografia Líquida de Alta Pressão , Glucose/metabolismo , Glicolipídeos/isolamento & purificação , Saccharomycetales/crescimento & desenvolvimento
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