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1.
Br J Dermatol ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34498260

RESUMO

BACKGROUND: Structural variations (SVs, defined as DNA variants ≥50 bp) have been associated with various complex human diseases. However, research to screen the whole genome for SVs predisposing to psoriasis is still lacking. OBJECTIVES: This study aimed to investigate the association of SVs and psoriasis. METHODS: We performed a genome-wide screen on SVs using an imputation method on 5 independent cohorts with 45,386 subjects from the Chinese Han population. Fine mapping analysis, genetic interaction analysis and RNA expression analysis were conducted to explore the mechanism of SVs. RESULTS: We obtained 4,535 SVs in total and identified 2 novel deletions (esv3608550, OR=2.73, P<2.00×10-308 ; esv3608542, OR=0.47, P=7.40×10-28 ) at 6q21.33 (MHC), 1 novel Alu element insertion (esv3607339, OR=1.22, P=1.18×10-35 ) at 5q33.3 (IL12B), and confirmed 1 previously reported deletion (esv3587563, OR=1.30, P=9.52×10-60 ) at 1q21.2 (LCE) for psoriasis. Fine mapping analysis including SNPs and small Insertions/Deletions (InDels) revealed that esv3608550 and esv3608542 were independently associated with psoriasis, and a novel independent SNP (rs9378188, OR=1.65, P=3.46×10-38 ) was identified at 6q21.33. By genetic interaction analysis and RNA expression analysis, we speculate that the association of 2 deletions at 6q21.33 with psoriasis might relate to their influence on the expression of HLA-C. CONCLUSIONS: Our study constructed the most comprehensive SV map for psoriasis thus far and enriched the genetic architecture and pathogenesis of psoriasis as well as highlighted the nonnegligible impact of SVs on complex diseases.

2.
Zhonghua Yi Xue Za Zhi ; 101(28): 2195-2202, 2021 Jul 27.
Artigo em Chinês | MEDLINE | ID: mdl-34333931

RESUMO

Objective: To investigate the effects of four therapeutic methods in the comprehensive treatment of China liver cancer staging (CNLC)Ⅱa~Ⅲa stage multiple hepatocellular carcinoma. Method: A retrospective study was conducted to collect clinical data of patients with multiple hepatocellular carcinoma (CNLC stage Ⅱa-Ⅲa), who received transhepatic arterial chemoembolization (TACE group, 73 cases), radiofrequency ablation (RFA group, 70 cases), TACE combined RFA (TACE combined RFA group, 69 cases) and surgical resection combined RFA (surgical resection combined RFA group, 57 cases) in the First Hospital of Lanzhou University from January 11, 2010 to January 31, 2017. The general data of age, gender, primary tumor, and laboratory examination were collected. The differences in overall survival rates and the survival rates among stratified subgrouping with different clinical factors between the four groups of patients were compared by the Kaplan-Meier method. Cox proportional hazards regression model analyzed the prognostic factors. Result: A total of 269 patients were enrolled and there were 194 males and 59 females with a median age of 58 years ranging from 23 to 84. The TACE group's 1, 3, and 5-year survival rates were 43.5%, 10.2%, and 0, respectively. The RFA group were 46.3%, 17.7%, and 0, respectively. The TACE combined RFA group were 56.8%, 21.5%, and 2.3%, respectively. The surgical resection combined RFA group was 76.5%, 38.7%, and 3.8%, respectively. The surgical resection combined RFA group has the best outcome(P<0.05). Univariate analysis showed that surgery combined RFA, tumor diameter<5 cm, no vascular invasion, preoperative AFP≤400 µg/L and TB<34 µmol/L are protective factors to improve the survival prognosis of patients with CNLCⅡa~Ⅲa stage multiple hepatocellular carcinoma(HR=0.784,0.718,0.633,0.846,0.617;all P<0.05). Multivariate Cox analysis showed that surgery combined RFA, tumor diameter<5 cm, preoperative AFP≤400 µg/L were independent risk prognostic factors for CNLCⅡa-Ⅲa stage multiple hepatocellular carcinoma (HR=0.702,0.743,0.647;all P<0.05). Conclusions: Surgical resection combined RFA is an effective method for the treatment of stage Ⅱa-Ⅲa hepatocellular carcinoma. Surgical resection combined RFA has more advantages in treatment patients with complicated hepatocellular carcinoma whose diameter<5 cm, tumor number<3, and preoperative AFP≤400 µg/L. Surgical resection combined RFA, tumor diameter<5 cm, preoperative AFP≤400 µg/L are independent influencing factors for the survival prognosis of patients with complicated hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular , Ablação por Cateter , Quimioembolização Terapêutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/terapia , China , Terapia Combinada , Feminino , Humanos , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
3.
Mycologia ; 113(1): 78-91, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33125292

RESUMO

A new species, Botrytis polygoni, was isolated from several species of Polygonaceae in 2011 and 2012 in Tongwei County, Gansu Province, China. The species infects Fagopyrum esculentum, F. tataricum, and Fallopia convolvulus, causing brown leaf spots and large blotches with concentric rings in the field. Botrytis polygoni is morphologically characterized by conidia spherical, unicellular, hyaline to pale brown or brown, (10.2-)14.3-21.4(-23.5) µm; and sclerotia black, spherical to subspherical, allantoid, or irregular-shaped, 0.2-4.1 × 0.1-3.0 mm. Comparison of the nuc rDNA internal transcribed spacer region (ITS1-5.8S-ITS2) sequences confirmed its placement in the genus Botrytis. Phylogenetic analysis based on the protein-coding genes glyceraldehyde 3-phosphate dehydrogenase (G3PDH), heat shock protein 60 (HSP60), and DNA-dependent RNA polymerase subunit II (RPB2) showed that the new species is clustered close but separate from Botrytis pyriformis, which was distant from 37 other Botrytis species and 17 undescribed species. Pathogenicity tests showed that the new species has aggressive pathogenicity to four species of Polygonaceae, specifically Fag. tataricum, Fal. convolvulus, Polygonum sibiricum, and Pol. aviculare, weak pathogenicity to Vicia faba in the Fabaceae, and no pathogenicity to eight other tested plants: Amaranthus retroflexus, Cirsium arvense, Convolvulus arvensis, Kalanchoe blossfeldiana, Lagopsis supine, Mentha canadensis, Plantago asiatica, and Raphanus sativus.

4.
Eur Rev Med Pharmacol Sci ; 24(21): 11334-11343, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33215453

RESUMO

Apoptin is a small molecular weight protein derived from chicken anemia virus, which can induce the apoptosis of transformed cells and tumor cells and leave primary and nontransformed cells unharmed. Apoptin's cell localization depends on its own phosphorylation state and cell type. In tumor cells, phosphorylated apoptin enters the nucleus and induces apoptosis. While, in normal cells apoptin mainly exists in the cytoplasm. Apoptin, as a disordered protein in cells, interacts with many proteins in cell signal pathways to induce apoptosis of tumor cells. The specific mechanism of apoptosis induced by apoptin has not been completely elucidated. Therefore, apoptin has become a potential anticancer agent. This review summarizes the research results of apoptin in our laboratory and reveals the specific antitumor mechanism of apoptin expressed by oncolytic virus vector on a variety of tumor cells and mouse models.


Assuntos
Antineoplásicos/metabolismo , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismo , Neoplasias/metabolismo , Vírus Oncolíticos/genética , Animais , Apoptose , Vírus da Anemia da Galinha/química , Humanos , Camundongos , Neoplasias/patologia , Neoplasias/terapia , Fosforilação
5.
Zhonghua Zhong Liu Za Zhi ; 41(9): 708-711, 2019 Sep 23.
Artigo em Chinês | MEDLINE | ID: mdl-31550863

RESUMO

Objective: To investigate the effect of omeprazole on plasma concentration, efficacy and adverse reactions of capecitabine in patients with colon cancer. Methods: Seventy-two patients with colon cancer treated with capecitabine were analysed retrospective. The patients treated with capecitabine combined with omeprazole were identified as experimental group and the capecitabine treatment alone as control group.The differences of blood concentration and the side effects of capecitabine between these two groups were compared. Results: The plasma concentration of 5-Fluorouracilum in experimental group was (126.25±50.59) µg/ml, without significant difference of (123.09±56.70) µg/ml in control group (P=0.121). The incidence of Ⅲ to Ⅳ degree bone marrow suppression, nausea, vomiting, diarrhea and hand-foot syndrome in experimental group were 13.8%, 0%, 0% and 19.4%, respectively. In control group, the incidence of Ⅲ to Ⅳ degree bone marrow suppression, nausea, vomiting, diarrhea and the hand-foot syndrome were 11.1%, 0%, 0% and 19.4%, respectively, without significant difference of experimental group (P>0.05). The incidence of acid reflux and heartburn in the control group was 72.2%, significantly higher than 44.4% of the experimental group (P<0.05). The objective response rate (ORR) and progression-free survival time (PFS) in these two groups were 30.6% and 33.3%, and 8.0 month and 8.5 month, respectively, without significant difference (P>0.05). Conclusion: The intravenous omeprazole attenuates reflux and heartburn of colon cancer patients treated with capecitabine, without affecting its plasma concentration and side effects and has no impact on the PFS of these patients.


Assuntos
Capecitabina/efeitos adversos , Capecitabina/sangue , Neoplasias do Colo/tratamento farmacológico , Omeprazol/efeitos adversos , Omeprazol/sangue , Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina/uso terapêutico , China/epidemiologia , Neoplasias do Colo/mortalidade , Intervalo Livre de Doença , Fluoruracila/administração & dosagem , Refluxo Gastroesofágico/induzido quimicamente , Refluxo Gastroesofágico/epidemiologia , Azia/induzido quimicamente , Azia/epidemiologia , Humanos , Omeprazol/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
6.
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi ; 33(5): 458-460;463, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31163558

RESUMO

Objective: To compare the diagnostic value of the 2015 American Thyroid Association(ATA) guidelines and the American College of Radiology Thyroid Imaging Reporting and Data System(ACR TI-RADS) classification for thyroid nodules. Method: Retrospective analysis of 340 cases of 386 thyroid nodules confirmed by surgery or pathology from November 2016 to November 2018 in Yan' an University Hospital was conducted, using 2015 ATA, ACR TI-RADS for classification. Histopathology or cytology was the gold standard, The receiver operating characteristic(ROC) curve was plotted, using χ test to compare the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the two methods. Result: Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of ACR TI-RADS were 961%, 741%, 645%, 974%, 813%, respectively, and the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the 2015 ATA guidelines was 937%, 733%, 632%, 960%, 801%,respectively. There was no statistically significant difference between the two groups. The area under ACR TI-RADS and 2015 ATA guide curve is 0851 and 0839, respectively. Conclusion: Both ACR TI-RADS and 2015 ATA guidelines have high diagnostic value. The two classification methods are equally effective in assessing the benign and malignant thyroid nodules.


Assuntos
Neoplasias da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/patologia , Humanos , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Ultrassonografia
7.
Zhonghua Yi Xue Za Zhi ; 99(20): 1562-1566, 2019 May 28.
Artigo em Chinês | MEDLINE | ID: mdl-31154723

RESUMO

Objective: To investigate the effect of Toll-like receptor 7 (TLR7) in CD8(+) T cells activity from patients with breast cancer. Methods: Thirty-three patients with breast cancer, twenty-three patients with benign breast tumor, and twenty healthy individuals were collected from The First Affiliated Hospital of Xinxiang Medical University between December 2017 and March 2018. Peripheral blood mononuclear cells (PBMCs) were isolated, and CD8(+) T cells were purified. TLR7 protein and mRNA relative expression in CD8(+) T cells was measured using flow cytometry and real-time PCR, respectively. mRNA relative expressions corresponding to perforin, granzyme B, and FasL in CD8(+) T cells were measured in response to TLR7 agonist stimulation. Direct/indirect contact co-culture system of CD8(+) T cells and breast cancer cell line MCF-7 was also used to assess cytolytic and noncytolytic function in response to TLR7 agonist CL097 stimulation. Results: The mean fluorescence intensity corresponding to TLR7 protein in CD8(+) T cells from breast cancer patients was 124.0±15.32, which was significantly down-regulated in comparison with benign breast tumor patients (255.5±54.91) and healthy individuals (261.9±68.65) (P<0.000 1). TLR7 mRNA relative level was also remarkably reduced in CD8(+) T cells from breast cancer patients (1.97±1.18) in comparison with benign breast tumor patients (4.84±1.01) and healthy individuals (4.75±1.40) (P<0.000 1). TLR7 agonist CL097 stimulation notably increased mRNA relative levels of perforin and granzyme B mRNA in CD8(+) T cells (P<0.01), but not elevated FasL mRNA (P>0.05).Furthermore, TLR7 agonist CL097 stimulation enhanced the cytolytic and noncytolytic function of CD8(+) T cells to MCF-7 cells, which presented as the elevation of target cell death and increase of interferon-γ production in direct and indirect contact co-culture system. Conclusion: TLR7 agonist promoted CD8(+) T cells function from breast cancer patients.


Assuntos
Neoplasias da Mama , Receptor 7 Toll-Like/metabolismo , Linfócitos T CD8-Positivos , Humanos , Leucócitos Mononucleares , Perforina
8.
Clin Exp Ophthalmol ; 47(6): 749-756, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31017701

RESUMO

IMPORTANCE: Management of cystic bleb leak is difficult. It would be essential to look for a method to strengthen the original pathological conjunctiva and reverse bleb leak. BACKGROUND: To evaluate the long-term efficacy and safety of collagen crosslinking in patients with leaking cystic bleb. DESIGN: Prospective interventional case series at a university-based hospital. PARTICIPANTS: Twelve eyes in 12 subjects with late-onset bleb leak from cystic bleb, without indications for prompt surgical interventions were included. METHODS: The subjects underwent crosslinking with 0.1% riboflavin application to bleb surface, followed by ultraviolet irradiation for 30 minutes. The subjects were followed up at baseline and at 1 week, 1 month, 3 months, 6 months post-treatment and then every 6 months afterwards. MAIN OUTCOME MEASURES: Interval from treatment to cessation of bleb leak, recurrence rate of bleb leak and side effects of treatment. RESULTS: The mean follow-up after crosslinking was 29.33 ± 12.45 months. Bleb leak subsided in 11 (92%) of 12 patients after a single session of crosslinking, after 1 to 8 weeks (median 3 weeks). Time to leak cessation was significantly correlated with the number of prior glaucoma interventions (R = .71, P = .014). Bleb wall at 3 months was significantly thicker than at baseline (0.70 ± 0.67 vs 0.81 ± 0.62 mm, P = .008). None of the patients experienced any complications. CONCLUSIONS AND RELEVANCE: Crosslinking achieves resolution of cystic bleb leak which lasts for at least 12 months, without the need of subsequent surgical interventions. Crosslinking is a simple, non-invasive treatment for bleb leak. It aims to restore the integrity of conjunctiva.


Assuntos
Colágeno/metabolismo , Túnica Conjuntiva/metabolismo , Reagentes para Ligações Cruzadas , Cirurgia Filtrante/efeitos adversos , Glaucoma de Ângulo Aberto/cirurgia , Hipotensão Ocular/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Hipotensão Ocular/etiologia , Hipotensão Ocular/metabolismo , Hipotensão Ocular/fisiopatologia , Fotoquimioterapia/métodos , Estudos Prospectivos , Riboflavina/uso terapêutico , Resultado do Tratamento , Raios Ultravioleta
9.
Zhonghua Xue Ye Xue Za Zhi ; 40(1): 17-23, 2019 Jan 14.
Artigo em Chinês | MEDLINE | ID: mdl-30704223

RESUMO

Objective: To analyze the clinical characteristics of recurrent thrombosis in patients with polycythemia vera (PV) and essential thrombocythemia (ET) to probe the risk factors for recurrent thrombosis in patients with ET and PV. Methods: The clinical data of 104 ET and PV patients with thrombosis in Beijing Anzhen Hospital from February 2001 to November 2016 were retrospectively analyzed. Thrombosis reoccurred in 38 patients. Statistical analyses were performed by multivariate logistic regression for risk factors of recurrent thrombosis in ET and PV patients. Results: Recurrent thrombosis occurred in 36.5% of patients with ET/PV, the total incidence rate in ET and PV patients was 9.8% patient-years, 12.3% patient-years and 5.7% patient-years in ET and PV respectively. There were a total of 56 re-thrombotic events, and 42.1% of events occurred within 1 year after the first thrombosis. The arterial re-thrombosis was 97.4% (most of acute coronary syndrome, ACS), and venous events was 2.6%. The most common cases of re-thrombosis were ACS in ET patients (18 cases, 64.3%), and cerebral infarction in PV patients (7 cases, 70.0%). The number of PV patients with 2 times or more re-thrombotic events was significantly higher than that of ET patients (9 cases, 90.0% vs 7 cases, 25.0%). The proportion of the patients with WBC>12.5×10(9)/L or Hct>45%, and thrombosis history or splenomegaly and high risk thrombotic events were higher than those with a single thrombus (52.6% vs 31.8%; 50.0% vs 30.0%; 86.8% vs 13.6%; 84.2% vs 33.3%; 52.6% vs 15.2%; 94.7% vs 53.0%; P values were 0.036,0.046, <0.001, <0.001, <0.001 and <0.001, respectively). Logistic regression analysis showed that thrombosis history (OR=13.697, P=0.025), splenomegaly (OR=13.301, P=0.034) and high risk stratification of thrombotic events (OR=44.618, P=0.025) were independent risk factors for recurrent thrombotic events. Conclusions: ET and PV patients had a higher risk of re-thrombosis. The incidence of re-thrombosis in ET was higher than in PV, ACS was more common cases of re-thrombotic events; but PV patients were more susceptible to multiple re-thromboses than ET ones, also with more cerebral infarction. Previous thrombus history, splenomegaly and high risk stratification of thrombotic events were independent risk predictors for re-thrombosis of ET and PV patients.


Assuntos
Policitemia Vera , Trombocitemia Essencial , Trombose , Humanos , Estudos Retrospectivos , Fatores de Risco
10.
Insect Mol Biol ; 28(3): 380-391, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30548717

RESUMO

Isopentenylation at A37 (i6 A37) of some transfer RNAs (tRNAs) plays a vital role in regulating the efficiency and fidelity of protein synthesis. However, whether insects, which are well known for their highly efficient protein synthesis machinery, employ this regulatory mechanism remains uninvestigated. In the current study, a candidate tRNA isopentenyltransferase (IPT) gene with three alternative splicing isoforms (BmIPT1-BmIPT3) was identified in Bombyx mori (silkworm). Only BmIPT1 could complement a yeast mutant lacking tRNA IPT. Phylogenetic analysis showed that silkworm tRNA IPT is conserved in the Lepidoptera. BmIPT was expressed in all B. mori tissues and organs that were investigated, but was expressed at a significantly higher level in silk glands of the fourth instar compared to the first day of the fifth instar. Interestingly, BmIPT was expressed at a significantly higher level in the domesticated silkworm, B. mori, than in wild Bombyx mandarina in multiple tissues and organs. Knock-down of BmIPT by RNA interference caused severe abnormalities in silk spinning and metamorphosis. Constitutive overexpression of BmIPT1 using a cytoplasmic actin 4 promoter in B. mori raised its messenger RNA level more than sixfold compared with nontransgenic insects and led to significant decreases in the body weight and cocoon shell ratio. Together, these results confirm the first functional tRNA IPT in insects and show that a suitable expression level of tRNA IPT is vital for silk spinning, normal growth, and metamorphosis. Thus, i6 A modification at position A37 in tRNA probably plays an important role in B. mori protein synthesis.


Assuntos
Alquil e Aril Transferases/genética , Bombyx/crescimento & desenvolvimento , Bombyx/genética , Proteínas de Insetos/genética , RNA de Transferência/genética , Alquil e Aril Transferases/química , Alquil e Aril Transferases/metabolismo , Sequência de Aminoácidos , Animais , Bombyx/metabolismo , Homeostase , Proteínas de Insetos/química , Proteínas de Insetos/metabolismo , Larva/genética , Larva/crescimento & desenvolvimento , Larva/metabolismo , Filogenia , Pupa/genética , Pupa/crescimento & desenvolvimento , Pupa/metabolismo , RNA de Transferência/metabolismo , Alinhamento de Sequência
11.
Zhonghua Yi Xue Za Zhi ; 98(40): 3240-3243, 2018 Oct 30.
Artigo em Chinês | MEDLINE | ID: mdl-30392288

RESUMO

Objective: To compare the effects of different types of anesthesia on postoperative cardiopulmonary complications in patients aged 80 years and above who received unilateral hip fracture surgery. Methods: The perioperative data of patients aged 80 and above who underwent unilateral hip fracture surgery in Peking Union Medical College Hospital from July 2009 to June 2014 were collected and grouped based on the types of anesthesia including general anesthesia, neuraxial anesthesia, and peripheral nerve block. Variables were analyzed including preoperative general conditions (age, sex, type of fracture, ASA physical status classification, preoperative cardiopulmonary complications), intraoperative conditions (type of surgical procedure, operative time, blood loss, total intraoperative fluid infusion), and postoperative conditions (length of hospital stay, postoperative hospital stay, ICU stay, postoperative newly developed cardiopulmonary complications, postoperative in-hospital death, hospitalization costs). The incidences of postoperative cardiopulmonary complications of each group were analyzed and compared. Results: A total of 219 cases were finally analyzed including general anesthesia (n=46), neuraxial anesthesia (n=90) and nerve block group (n=83). Fewer cases with preoperative pulmonary complications were noticed in general anesthesia group (15 cases, 32.6%) than in neuraxial anesthesia group (45 cases, 50%) and nerve block group (47 cases, 56.6%) (χ(2)=6.912, P=0.032). No statistical differences were found between groups regarding preoperative cardiovascular complications and other variables. There were no significant differences in postoperative cardiopulmonary complications. However, the cost of hospitalization was lower in neuraxial anesthesia group (45.6±21.4) thousand RMB and nerve block group (48.2±25.8) thousand RMB compared with general anesthesia group (56.3±21.6) thousand RMB, the difference was statistically significant(F=9.951, P=0.007). Conclusions: For elderly patients undergoing unilateral hip surgery, the type of anesthesia does not affect the incidence of postoperative cardiopulmonary complications. However, neuraxial anesthesia and nerve block may reduce the cost of hospitalization.


Assuntos
Anestesia Geral , Fraturas do Quadril , Idoso de 80 Anos ou mais , Humanos , Bloqueio Nervoso , Complicações Pós-Operatórias , Estudos Retrospectivos , Resultado do Tratamento
12.
J Dent Res ; 97(2): 155-162, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28910570

RESUMO

Tooth agenesis is one of the most common developmental anomalies affecting function and esthetics. The paired-domain transcription factor, Pax9, is critical for patterning and morphogenesis of tooth and taste buds. Mutations of PAX9 have been identified in patients with tooth agenesis. Despite significant progress in the genetics of tooth agenesis, many gaps in knowledge exist in refining the genotype-phenotype correlation between PAX9 and tooth agenesis. In the present study, we complete genetic and phenotypic characterization of multiplex Chinese families with nonsyndromic (NS) tooth agenesis. Direct sequencing of polymerase chain reaction products revealed 9 novel (c.140G>C, c.167T>A, c.332G>C, c.194C>A, c.271A>T, c.146delC, c.185_189dup, c.256_262dup, and c.592delG) and 2 known heterozygous mutations in the PAX9 gene among 120 probands. Subsequently, pedigrees were extended, and we confirmed that the mutations co-segregated with the tooth agenesis phenotype (with exception of families in which DNA analysis was not available). In 1 family ( n = 6), 2 individuals harbored both the PAX9 c.592delG mutation and a heterozygous missense mutation (c.739C>T) in the MSX1 gene. Clinical characterization of families segregating a PAX9 mutation reveal that all affected individuals were missing the mandibular second molar and their maxillary central incisors are most susceptible to microdontia. A significant reduction of bitter taste perception was documented in individuals harboring PAX9 mutations ( n = 3). Functional studies revealed that PAX9 haploinsufficiency or a loss of function of the PAX9 protein underlies tooth agenesis.


Assuntos
Anodontia/genética , Análise Mutacional de DNA , Fator de Transcrição PAX9/genética , Adolescente , Adulto , Criança , China , Ensaio de Desvio de Mobilidade Eletroforética , Feminino , Imunofluorescência , Estudos de Associação Genética , Humanos , Fator de Transcrição MSX1/genética , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Linhagem , Reação em Cadeia da Polimerase , Distúrbios do Paladar/genética
13.
Zhonghua Xue Ye Xue Za Zhi ; 38(10): 825-830, 2017 Oct 14.
Artigo em Chinês | MEDLINE | ID: mdl-29166732

RESUMO

Objective: To evaluate the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in prophylaxis neutropenia after chemotherapy in patients with lymphoma. Methods: This was a multicenter, single arm, open, phase Ⅳ clinical trial. Included 410 patients with lymphoma received multiple cycles of chemotherapy and PEG-rhG-CSF was administrated as prophylactic. The primary endpoint was the incidence of Ⅲ/Ⅳ grade neutropenia and febrile neutropenia (FN) after each chemotherapy cycle. Meanwhile the rate of antibiotics application during the whole period of chemotherapy was observed. Results: ①Among the 410 patients, 8 cases (1.95%) were contrary to the selected criteria, 35 cases (8.54%) lost, 19 cases (4.63%) experienced adverse events, 12 cases (2.93%) were eligible for the termination criteria, 15 cases (3.66%) develpoed disease progression or recurrence, thus the rest 321 cases (78.29%) were into the Per Protocol Set. ②During the first to fourth treatment cycles, the incidences of grade Ⅳ neutropenia after prophylactic use of PEG-rhG-CSF were 19.14% (49/256) , 12.5% (32/256) , 12.18% (24/197) , 13.61% (20/147) , respectively. The incidences of FN were 3.52% (9/256) , 0.39% (1/256) , 2.54% (5/197) , 2.04% (3/147) , respectively. After secondary prophylactic use of PEG-rhG-CSF, the incidences of Ⅳ grade neutropenia decreased from 61.54% (40/65) in the screening cycle to 16.92% (11/65) , 18.46% (12/65) and 20.75% (11/53) in 1-3 cycles, respectively. The incidences of FN decreased from 16.92% (11/65) in the screening cycle to 1.54% (1/65) , 4.62% (3/65) , 3.77% (2/53) in 1-3 cycles, respectively. ③The proportion of patients who received antibiotic therapy during the whole period of chemotherapy was 34.39% (141/410) . ④The incidence of adverse events associated with PEG-rhG-CSF was 4.63% (19/410) . The most common adverse events were bone pain[3.90% (16/410) ], fatigue (0.49%) and fever (0.24%) . Conclusion: During the chemotherapy in patients with lymphoma, the prophylactic use of PEG-rhG-CSF could effectively reduce the incidences of grade Ⅲ/Ⅳ neutropenia and FN, which ensures that patients with lymphoma receive standard-dose chemotherapy to improve its cure rate.


Assuntos
Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Neutropenia/induzido quimicamente , Neutropenia/prevenção & controle , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Neoplasias Pulmonares , Linfoma , Recidiva Local de Neoplasia , Estudos Prospectivos , Proteínas Recombinantes
14.
Methods Enzymol ; 585: 377-395, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28109439

RESUMO

Mass spectrometry-based proteomics has experienced an unprecedented advance in comprehensive analysis of proteins and posttranslational modifications, with particular technical progress in liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) and isobaric labeling multiplexing capacity. Here, we introduce a deep proteomics profiling protocol that combines 10-plex tandem mass tag (TMT) labeling with an optimized LC-MS/MS platform to quantitate whole proteome and phosphoproteome. The major steps include protein extraction and digestion, TMT labeling, two-dimensional liquid chromatography, TiO2-mediated phosphopeptide enrichment, high-resolution mass spectrometry, and computational data processing. This protocol routinely leads to confident quantification of more than 10,000 proteins and approximately 30,000 phosphosites in mammalian samples. Quality control steps are implemented for troubleshooting and evaluating experimental variation. Such a multiplexed robust method provides a powerful tool for dissecting proteomic signatures at the systems level in a variety of complex samples, ranging from cell culture, animal tissues to human clinical specimens.


Assuntos
Cromatografia Líquida/métodos , Fosfoproteínas/análise , Proteoma/análise , Proteômica/métodos , Espectrometria de Massas em Tandem/métodos
15.
Hum Exp Toxicol ; 36(10): 1087-1099, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27920337

RESUMO

Acrylamide (ACR) is a chemical intermediate utilized in industry. ACR is also formed during heating of foods containing carbohydrates and amino acids. Therefore, humans are widely exposed to ACR, and ACR neurotoxicity in humans is a significant public health issue attracting wide attention. In this study, we investigated the potential neuroprotective effects of epigallocatechin-3-gallate (EGCG), the most abundant polyphenolic compound in green tea, in PC12 cells treated with ACR. ACR-treated PC12 cells pretreated with various concentrations of EGCG (2.5, 5 and 10 µM) for 24 h had increased viability and acetylcholinesterase activity and reduced apoptosis and necrosis compared to cells exposed to ACR alone. EGCG reduced the expression of bax mRNA, decreased cytochrome c release, reduced intracellular calcium levels, inactivated caspase 3 and increased mitochondrial membrane potential, suggesting that EGCG prevents ACR-induced apoptosis through a mitochondrial-mediated pathway. In addition, EGCG inhibited the formation of reactive oxygen species and lipid peroxidation while enhancing superoxide dismutase activity and glutathione levels, thereby reducing oxidative stress. Our results indicate that pretreatment of PC12 cells with EGCG attenuates ACR-induced apoptosis by reducing oxidative stress. Therefore, drinking green tea may reduce nerve injury induced by ACR.


Assuntos
Acrilamida/toxicidade , Catequina/análogos & derivados , Fármacos Neuroprotetores/farmacologia , Acetilcolinesterase/metabolismo , Animais , Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Caspase 3/metabolismo , Catequina/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Citocromos c/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Ratos , Espécies Reativas de Oxigênio/metabolismo
16.
Beijing Da Xue Xue Bao Yi Xue Ban ; 48(1): 686-91, 2016 Feb 18.
Artigo em Chinês | MEDLINE | ID: mdl-27538153

RESUMO

OBJECTIVE: To screen the ectodysplasin A (EDA) gene mutation in the patients with non-syndromic tooth agenesis and ectodermal dysplasia, and to analyze the phenotype of missing teeth pattern in these two groups of patients. METHODS: In the study, 174 patients with tooth agenesis (143: non-syndromic, 31: ectodermal dysplasia) and 451 health control volunteers were enrolled from the clinic, and the genome DNA was extracted from either peripheral blood or oral mucosal swab. The coding region of EDA gene was then amplified by PCR, sequenced and blasted to online NCBI database. The missing teeth were recorded for all patients, and the missing teeth from patients with EDA mutation were compared among the different dentition sites. RESULTS: 33 patients were identified with EDA mutation. In the non-syndromic patients, 13/143(9.09%) were identified with EDA mutation, while in patients with ectodermal dysplasia, 20/31(64.52%) were found with EDA mutation. Ten novel EDA mutations were identified (c.769G>C[p.G257R ],c.936C>G[p.I312M],c.223G>A[p.E75K], .1166C>T[p.P389L],c.133G>C[p.G45R],c.1109G>A[p.E370K],c.914G>T[p.S305I], c.916C>T[p.Q306X],c.602G>T[p.G201V],c.88-89insG[p.A30GfsX69]). For each dentition site there was no statistic difference in the number of missing teeth between the left and right sides, so the number from both sides were combined later in the analysis. In the patients with EDA mutation, the non-syndromic patients had fewer missing teeth (15.9±6.4 missing teeth for each, 207/364 in total) than the patients with ectodermal dysplasia (23.9±4.3, 478/560). In the non-syndromic patients with EDA mutation, the maxillay central incisors and first molars were less affected, with the same missing rate as 19.2% (5/26). While the mandibular central incisors (with a missing rate of 76.9%, 20/26), the maxillary lateral incisors (the missing rate: 88.5%, 23/26), the mandibular lateral incisors (the missing rate: 80.8%, 21/26), and the maxillary first premolars (the missing rate: 80.8%, 21/26) were more likely to be missing. In the ectodermal dysplasia patients with EDA mutation, only maxillary central incisors (the missing rate: 60%, 24/40), maxillary canines (the missing rate: 70%, 28/40), mandibular canines (the missing rate: 67.5%, 27/40), maxillary first molars (the missing rate: 65%, 26/40) and mandibular first molars (the missing rate: 72.5%, 29/40) had higher possibility of persistence. Teeth at other dentition sites were more likely to be affected (the minimum missing rate: 87.5%, 35/40). CONCLUSION: The findings would help to reveal the EDA gene and its function in ectodermal organogenesis.

17.
J Biol Regul Homeost Agents ; 30(2): 505-10, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27358139

RESUMO

The purpose of this study was to evaluate the clinical effect of embolic microspheres in the treatment of primary hepatic carcinoma. Fifty-eight patients who were confirmed with primary hepatic carcinoma by imaging were retrospectively analyzed. They were firstly perfused with 50 mg of oxaliplatin and 40 mg of epirubicin. Embolic microspheres were then injected into the distal end of targeted blood vessels. After this procedure, dynamic observation was carried out until tumor stain disappeared. Liver function and blood indexes were reexamined on days 5, 6, 7 and 28 after treatment, and moreover, the liver was examined with Magnetic Resonance Imaging (MRI) or computed tomography (CT). Compared to traditional lipiodol embolization, embolic microspheres did not aggregate the damage on liver function and the imaging examination suggested necrosis of some tumor tissues. Embolic microspheres proved to be effective in treating primary hepatic carcinoma. It produces no damage on liver function and can lead to significant shrinkage of hepatic carcinoma and necrosis of some tumor tissues. Embolic microspheres, which merely block distal branches of tumor-feeding artery, can avoid collateral circulation induced by permanent blocking, thus achieve a good treatment effect.


Assuntos
Carcinoma Hepatocelular/terapia , Embolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Microesferas , Adulto , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
18.
Beijing Da Xue Xue Bao Yi Xue Ban ; 48(4): 686-691, 2016 Aug 18.
Artigo em Chinês | MEDLINE | ID: mdl-29263514

RESUMO

OBJECTIVE: To screen the ectodysplasin A (EDA) gene mutation in the patients with non-syndromic tooth agenesis and ectodermal dysplasia, and to analyze the phenotype of missing teeth pattern in these two groups of patients. METHODS: In the study, 174 patients with tooth agenesis (143: non-syndromic, 31: ectodermal dysplasia) and 451 health control volunteers were enrolled from the clinic, and the genome DNA was extracted from either peripheral blood or oral mucosal swab. The coding region of EDA gene was then amplified by PCR, sequenced and blasted to online NCBI database. The missing teeth were recorded for all patients, and the missing teeth from patients with EDA mutation were compared among the different dentition sites. RESULTS: 33 patients were identified with EDA mutation. In the non-syndromic patients, 13/143(9.09%) were identified with EDA mutation, while in patients with ectodermal dysplasia, 20/31(64.52%) were found with EDA mutation. Ten novel EDA mutations were identified (c.769G>C[p.G257R ],c.936C>G[p.I312M],c.223G>A[p.E75K], .1166C>T[p.P389L],c.133G>C[p.G45R],c.1109G>A[p.E370K],c.914G>T[p.S305I], c.916C>T[p.Q306X],c.602G>T[p.G201V],c.88-89insG[p.A30GfsX69]). For each dentition site there was no statistic difference in the number of missing teeth between the left and right sides, so the number from both sides were combined later in the analysis. In the patients with EDA mutation, the non-syndromic patients had fewer missing teeth (15.9±6.4 missing teeth for each, 207/364 in total) than the patients with ectodermal dysplasia (23.9±4.3, 478/560). In the non-syndromic patients with EDA mutation, the maxillay central incisors and first molars were less affected, with the same missing rate as 19.2% (5/26). While the mandibular central incisors (with a missing rate of 76.9%, 20/26), the maxillary lateral incisors (the missing rate: 88.5%, 23/26), the mandibular lateral incisors (the missing rate: 80.8%, 21/26), and the maxillary first premolars (the missing rate: 80.8%, 21/26) were more likely to be missing. In the ectodermal dysplasia patients with EDA mutation, only maxillary central incisors (the missing rate: 60%, 24/40), maxillary canines (the missing rate: 70%, 28/40), mandibular canines (the missing rate: 67.5%, 27/40), maxillary first molars (the missing rate: 65%, 26/40) and mandibular first molars (the missing rate: 72.5%, 29/40) had higher possibility of persistence. Teeth at other dentition sites were more likely to be affected (the minimum missing rate: 87.5%, 35/40). CONCLUSION: The findings would help to reveal the EDA gene and its function in ectodermal organogenesis.


Assuntos
Anodontia/genética , Ectodisplasinas/genética , Fenótipo , Sequência de Bases , Humanos , Mutação
19.
Osteoarthritis Cartilage ; 24(3): 514-20, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26485068

RESUMO

OBJECTIVE: To evaluate the efficacy of Danshen on histological parameters and antioxidative activity in the articular cartilage of rabbits with osteoarthritis (OA). DESIGN: Twenty-four rabbits were randomly divided into three groups (control, OA, and Danshen OA; eight rabbits per group). Anterior cruciate ligament transection (ACLT) of the left hind knees was performed in all rabbits in the OA and Danshen OA group for induction of OA. The rabbits in the control group underwent a sham operation. After surgery, 3 g/kg body weight of Danshen granules dissolved in 5 mL distilled water was administered by gastric intubation once per day and over a 6-week period to the Danshen OA group. The same volume of distilled water was administered to the OA and control groups. After 6 weeks, the medial femoral condyles and synoviums of the left hind knees in all three groups were harvested and used for histological and biochemical analyses. RESULTS: Severe articular cartilage degeneration as well as lower proteoglycan (PG) content were noted in the OA group compared to the Danshen OA group (P < 0.05). The glutathione (GSH) levels in the synovium and articular cartilage of the rabbits in the Danshen OA group were significantly higher compared to the OA group (P < 0.001). The malondialdehyde (MDA) levels of the synovium and articular cartilage in the Danshen OA group was markedly depleted compared to the OA group (P < 0.001). CONCLUSION: Danshen can prevent articular cartilage degeneration in OA through the defense against oxidative stress.


Assuntos
Antioxidantes/uso terapêutico , Artrite Experimental/prevenção & controle , Doenças das Cartilagens/prevenção & controle , Cartilagem Articular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/uso terapêutico , Osteoartrite/prevenção & controle , Animais , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Doenças das Cartilagens/metabolismo , Doenças das Cartilagens/patologia , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Glutationa/metabolismo , Masculino , Malondialdeído/metabolismo , Osteoartrite/metabolismo , Osteoartrite/patologia , Estresse Oxidativo/efeitos dos fármacos , Proteoglicanas/metabolismo , Coelhos , Distribuição Aleatória , Membrana Sinovial/metabolismo
20.
Dis Esophagus ; 29(7): 740-746, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26316375

RESUMO

The objective of this study was to investigate the prognostic value of peripheral blood monocytes in esophageal squamous cell carcinoma (ESCC) patients who underwent esophagectomy. Records from 218 consecutive patients with histologically diagnosed ESCC who underwent esophagectomy at Qilu Hospital of Shandong University from January 2007 to December 2008 were retrospectively reviewed. The median disease-free survival (DFS) of this cohort was 29.0 months, and the 5-year DFS rate was 34.4%. The median overall survival (OS) was 35.0 months, and the 5-year OS rate was 37.6%. The cut-off value of 0.42 × 109 /L for the absolute monocyte count (AMC) was chosen as optimal to discriminate between survival and death by applying receiver operating curve analysis. There were 131 patients (60.1%) who had high AMC (≥0.42 × 109 /L) preoperatively. We found that AMC was significantly associated with gender, tumor location, and platelet count. Kaplan-Meier survival analysis of patients with high preoperative AMC had a significant worse prognosis for DFS (high vs. low: 27.5% vs. 39.0%, P = 0.015) and OS (high vs. low: 31.1% vs. 44.8%, P = 0.009) than those with low preoperative AMC. In a multivariate analysis, preoperative AMC was an independent prognostic factor for DFS (P = 0.025, hazard ratio [HR]: 1.469, 95% confidence interval [CI]: 1.050-2.054) and OS (P = 0.015, HR: 1.547, 95% CI: 1.088-2.200). In addition, among 140 patients without both preoperative and postoperative therapy, significantly worse OS (P = 0.012) and marginally reduced DFS (P = 0.079) were found in the high AMC cohort versus the low AMC cohort. A higher preoperative absolute peripheral monocyte count can be considered as a useful prognostic marker of ESCC patients who underwent esophagectomy.


Assuntos
Carcinoma de Células Escamosas/sangue , Neoplasias Esofágicas/sangue , Esofagectomia/mortalidade , Contagem de Leucócitos , Monócitos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Período Pré-Operatório , Estudos Retrospectivos , Taxa de Sobrevida
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