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1.
J Clin Pharmacol ; 64(6): 672-684, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38363006

RESUMO

The aim of this study was to use a combination of physiologically based pharmacokinetic (PBPK) modeling and urinary glucose excretion (UGE) modeling to predict the time profiles of pharmacokinetics (PK) and UGE for the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (EMP). Additionally, the study aims to explore the compensatory effect of SGLT1 in renal glucose reabsorption (RGR) when SGLT2 is inhibited. The PBPK-UGE model was developed using physicochemical and biochemical properties, renal physiological parameters, binding kinetics, glucose, and Na+ reabsorption kinetics by SGLT1/2. For area under the plasma concentration-time curve, maximum plasma concentration, and cumulative EMP excretion in urine, the predicted values fell within a range of 0.5-2.0 when compared to observed data. Additionally, the simulated UGE data also matched well with the clinical data, further validating the accuracy of the model. According to the simulations, SGLT1 and SGLT2 contributed approximately 13% and 87%, respectively, to RGR in the absence of EMP. However, in the presence of EMP at doses of 2.5 and 10 mg, the contribution of SGLT1 to RGR significantly increased to approximately 76%-82% and 89%-93%, respectively, in patients with type 2 diabetes mellitus. Furthermore, the model supported the understanding that the compensatory effect of SGLT1 is the underlying mechanism behind the moderate inhibition observed in total RGR. The PBPK-UGE model has the capability to accurately predict the PK and UGE time profiles in humans. Furthermore, it provides a comprehensive analysis of the specific contributions of SGLT1 and SGLT2 to RGR in the presence or absence of EMP.


Assuntos
Compostos Benzidrílicos , Glucosídeos , Modelos Biológicos , Transportador 1 de Glucose-Sódio , Inibidores do Transportador 2 de Sódio-Glicose , Glucosídeos/farmacocinética , Humanos , Compostos Benzidrílicos/farmacocinética , Compostos Benzidrílicos/urina , Transportador 1 de Glucose-Sódio/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/farmacocinética , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Glucose/metabolismo , Masculino , Transportador 2 de Glucose-Sódio/metabolismo , Adulto , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/farmacologia , Reabsorção Renal/efeitos dos fármacos , Rim/metabolismo , Glicosúria , Feminino , Pessoa de Meia-Idade
2.
Yi Chuan ; 45(10): 922-932, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37872114

RESUMO

This study aimed to assess and compare the performance of different machine learning models in predicting selected pig growth traits and genomic estimated breeding values (GEBV) using automated machine learning, with the goal of optimizing whole-genome evaluation methods in pig breeding. The research employed genomic information, pedigree matrices, fixed effects, and phenotype data from 9968 pigs across multiple companies to derive four optimal machine learning models: deep learning (DL), random forest (RF), gradient boosting machine (GBM), and extreme gradient boosting (XGB). Through 10-fold cross-validation, predictions were made for GEBV and phenotypes of pigs reaching weight milestones (100 kg and 115 kg) with adjustments for backfat and days to weight. The findings indicated that machine learning models exhibited higher accuracy in predicting GEBV compared to phenotypic traits. Notably, GBM demonstrated superior GEBV prediction accuracy, with values of 0.683, 0.710, 0.866, and 0.871 for B100, B115, D100, and D115, respectively, slightly outperforming other methods. In phenotype prediction, GBM emerged as the best-performing model for pigs with B100, B115, D100, and D115 traits, achieving prediction accuracies of 0.547, followed by DL at 0.547, and then XGB with accuracies of 0.672 and 0.670. In terms of model training time, RF required the most time, while GBM and DL fell in between, and XGB demonstrated the shortest training time. In summary, machine learning models obtained through automated techniques exhibited higher GEBV prediction accuracy compared to phenotypic traits. GBM emerged as the overall top performer in terms of prediction accuracy and training time efficiency, while XGB demonstrated the ability to train accurate prediction models within a short timeframe. RF, on the other hand, had longer training times and insufficient accuracy, rendering it unsuitable for predicting pig growth traits and GEBV.


Assuntos
Genoma , Modelos Genéticos , Suínos/genética , Animais , Fenótipo , Genômica/métodos , Genótipo , Polimorfismo de Nucleotídeo Único
3.
International Eye Science ; (12): 1554-1558, 2022.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-940022

RESUMO

AIM: To observe the safety and efficacy of stab incision glaucoma surgery(SIGS)in the treatment of adult glaucoma.METHODS: A series of retrospective case studies were carried out from June 2018 to November 2020, the clinical data of 55 cases with 70 eyes of glaucoma treated with SIGS in our hospital were collected. Following up at 6mo after operation, the intraocular pressure(IOP), bleb and postoperative complications were observed.RESULTS: Among the included patients, 30 eyes were performed SIGS alonely, 40 eyes were performed SIGS combined with phacoemulsification. Among them, the operation of 33 eyes(47%)was completely successful, the operation of 28 eyes(40%)was partially successful, and the operation of 9 eyes(13%)were failed. The mean preoperative IOP under medication was 31.82±13.16mmHg, and at 1wk, 1, 3 and 6mo after operation, the mean IOP(14.97±5.25, 17.94±5.24, 18.43±4.74, 17.37±3.36)mmHg were all significantly lower than before operation, and the number of IOP-lowering drugs used at 6mo after operation [0(0, 1)] was significantly lower than before operation [3(2, 3)](P<0.001). At 6mo after operation, the filtering blebs' shape of the patients: 30 eyes(43%)of type I(functional bleb), 31 eyes(44%)of type Ⅱ(functional bleb), 7 eyes(10%)of type Ⅲ(flat bleb)and 2 eyes(3%)of type IV(encapsulated vesicular bleb)were included. During the follow-up period, 2 eyes had hyphema in anterior chamber, 4 eyes had inflammatory reaction in anterior chamber, 3 eyes had low IOP, shallow anterior chamber and excessive filtration, 1 eye had malignant glaucoma, 1 eye had endophthalmitis, 1 eye had choroidal detachment, 1 eye had choroidal detachment, and 9 eyes had scarring of filtering blebs.CONCLUSION: SIGS is effective in the treatment of primary open angle glaucoma, primary angle-closure glaucoma and some secondary glaucoma without serious complications.

4.
International Eye Science ; (12): 623-628, 2022.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-922864

RESUMO

@#AIM: To explore the risk factors of xerophthalmia after cataract surgery in patients with type 2 diabetes mellitus, and to construct a risk prediction model.METHODS: A total of 212 patients(212 eyes)with type 2 diabetes who underwent cataract surgery in our hospital from April 2019 to April 2021 were selected. The patients were divided into dry eye group(43 cases, 43 eyes)and non-xerophthalmia eye(169 cases, 169 eyes). The general data, laboratory examination index and quality of life score of the two groups were compared; multivariate Logistic regression analysis was used to analyze the risk factors of postoperative xerophthalmia; constructed a line chart prediction model and evaluated its prediction accuracy. RESULTS: There were significant differences in the history of keratoconjunctival disease, pterygium, meibomian gland dysfunction, lens nucleus hardness, disease cognition, postoperative anxiety, postoperative depression, surgical incision, medication compliance, and the levels of interleukin-1β(IL-1β), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α)and HbA1c at 1wk after operation between the two groups(<i>P</i><0.05). The results of multivariate Logistic regression analysis showed that postoperative anxiety, postoperative depression, 3.0mm of surgical incision, IL-1β>31.26ng/mL, IL-6>29.42ng/mL, TNF-α>77.68ng/mL and HbA1c≥6.50% were risk factors for postoperative xerophthalmia(<i>P</i><0.05). The calibration curve and standard curve of the nomogram prediction model were fit well, and the prediction probabilities were mostly distributed around 0 and 1, with high accuracy.The visual function evaluation, environmental trigger factors, ocular discomfort symptoms and ocular surface disease index(OSDI)score in the dry eye group was significantly higher than those in the non-xerophthalmia group(<i>P</i><0.05). CONCLUSION: Surgical incision, postoperative anxiety, depression, medication compliance, serum inflammatory factors and HbA1c are all related to xerophthalmia after cataract surgery in patients with type 2 diabetes. Early identification of risk factors and timely intervention are helpful to reduce the incidence of postoperative xerophthalmia and improve the quality of life.

5.
Tumour Biol ; 39(2): 1010428317691188, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28240050

RESUMO

Osteosarcomas are common bone malignancies in children and adolescents. LDOC1 (leucine zipper, down-regulated in cancer 1), a tumor suppressor, is down-regulated in many cancers. In this study, we investigated the role of LDOC1 in tumor metastasis and its prognostic significance in osteosarcomas. We established osteosarcoma cells stably expressing LDOC1, driven by an HIV-based lentiviral system. We investigated the impact of LDOC1 on migration and invasion abilities in these cells using a transwell assay. LDOC1-associated changes in expression of metastasis-promoting genes were analyzed with a quantitative real-time polymerase chain reaction primer array. A xenograft tumor model (n = 7 mice/group) was used to assess the effect of LDOC1 on osteosarcoma metastasis in vivo. The overall survival and disease-free survival of osteosarcoma patients (n = 74) were analyzed retrospectively based on immunohistochemical analysis of LDOC1 levels in tumors and Kaplan-Meier analysis. LDOC1-expressing osteosarcoma cells displayed decreased migration and invasion in vitro. The quantitative real-time polymerase chain reaction primer array data showed that increased LDOC1 expression up-regulated many metastasis-suppressor genes. In the xenograft model, micro-computed tomography imaging data indicated that increased LDOC1 expression is associated with weaker lung metastasis ability. The Wnt5a signaling pathway promotes osteosarcoma metastasis; LDOC1 expression decreased Wnt5a levels in osteosarcoma cells. Kaplan-Meier analysis showed that higher LDOC1 expression was associated with improved osteosarcoma patient overall survival and disease free survival (p = 0.022). Our data show that LDOC1 is a tumor suppressor in osteosarcoma, and that it regulates metastasis of osteosarcoma cells. Furthermore, LDOC1 might be a valuable prognostic marker in osteosarcomas.


Assuntos
Proteínas Nucleares/biossíntese , Proteínas Supressoras de Tumor/biossíntese , Proteína Wnt-5a/biossíntese , Adolescente , Adulto , Animais , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Criança , Xenoenxertos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Pessoa de Meia-Idade , Proteínas Nucleares/metabolismo , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Proteínas Supressoras de Tumor/metabolismo , Via de Sinalização Wnt , Proteína Wnt-5a/metabolismo , Adulto Jovem
6.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-659658

RESUMO

Objective To study and analyze the effect of clozapine treatment and rehabilitation nursing on social dysfunction of schizophrenia. Methods 88 patients with schizophrenia in Tongde Hospital were selected as the subjects. The control group was treated with clozapine, with an initial dose of 50 mg, once a day. On the basis of the experimental group received rehabilitation nursing measures, health education, establishing harmonious doctor-patient relationship, according to the actual situation of patients received psychological counseling measures, pay attention to patients with mood changes, the patients were encouraged to manual labor and rehabilitation activities. Results Before treatment, the scores of social function disability screening scale of the experimental group and the control group were (6.89±1.65) points and (6.57±1.63) points, and the difference between the two groups was not statistically significant. After treatment, the defect score of the experimental group was (4.32 ±1.10), significantly lower than the control group, the scale score was (5.67 ± 1.37), and the difference between the two groups was statistically significant (P<0.05). Conclusion Clozapine combined with rehabilitation nursing in the treatment of schizophrenia social function defects, the clinical efficacy is ideal, can significantly improve the social function defects of patients, and has clinical significance.

7.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-657500

RESUMO

Objective To study and analyze the effect of clozapine treatment and rehabilitation nursing on social dysfunction of schizophrenia. Methods 88 patients with schizophrenia in Tongde Hospital were selected as the subjects. The control group was treated with clozapine, with an initial dose of 50 mg, once a day. On the basis of the experimental group received rehabilitation nursing measures, health education, establishing harmonious doctor-patient relationship, according to the actual situation of patients received psychological counseling measures, pay attention to patients with mood changes, the patients were encouraged to manual labor and rehabilitation activities. Results Before treatment, the scores of social function disability screening scale of the experimental group and the control group were (6.89±1.65) points and (6.57±1.63) points, and the difference between the two groups was not statistically significant. After treatment, the defect score of the experimental group was (4.32 ±1.10), significantly lower than the control group, the scale score was (5.67 ± 1.37), and the difference between the two groups was statistically significant (P<0.05). Conclusion Clozapine combined with rehabilitation nursing in the treatment of schizophrenia social function defects, the clinical efficacy is ideal, can significantly improve the social function defects of patients, and has clinical significance.

8.
Chemistry ; 22(31): 10969-75, 2016 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-27362319

RESUMO

P450 119 peroxygenase and its site-directed mutants are discovered to catalyze the enantioselective epoxidation of methyl-substituted styrenes. Two new site-directed P450 119 mutants, namely T213Y and T213M, which were designed to improve the enantioselectivity and activity for the epoxidation of styrene and its methyl substituted derivatives, were studied. The T213M mutant is found to be the first engineered P450 peroxygenase that shows highly enantioselective epoxidation of cis-ß-methylstyrenes, with up to 91 % ee. Molecular modeling studies provide insights into the different catalytic activity of the T213M mutant and the T213Y mutant in the epoxidation of cis-ß-methylstyrene. The results of the calculations also contribute to a better understanding of the substrate specificity and configuration control for the regio- and stereoselective peroxygenation catalyzed by the T213M mutant.


Assuntos
Compostos de Epóxi/química , Oxigenases de Função Mista/química , Engenharia de Proteínas/métodos , Estireno/química , Catálise , Modelos Moleculares , Estereoisomerismo
9.
Molecules ; 21(1): E112, 2016 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-26797597

RESUMO

An enantioselective total synthesis of chiral falcarindiol analogues from buta-1,3-diyn-1-yltriisopropylsilane is reported. The key step in this synthesis is BINOL-promoted asymmetric diacetylene addition to aldehydes. The two chiral centers of the falcarindiol analogues can be produced by using the same kind of catalyst with high selectivity, and the final product can be obtained in only six steps.


Assuntos
Aldeídos/química , Alcinos/química , Di-Inos/química , Álcoois Graxos/química , Naftóis/química , Catálise , Di-Inos/síntese química , Ésteres , Álcoois Graxos/síntese química , Estrutura Molecular
10.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 43(3): 298-304, 2014 05.
Artigo em Chinês | MEDLINE | ID: mdl-24998653

RESUMO

OBJECTIVE: To investigate the effect of atorvastatin on exercise tolerance in patients with diastolic dysfunction and exercise-induced hypertension. METHODS: A randomized, double-blind, placebo-controlled prospective study was performed. Sixty patients with diastolic dysfunction (mitral flow velocity E/A <1) and exercise-induced hypertension (SBP>200 mm Hg) treated with atorvastatin (20 mg q.d) or placebo for 1 year. Cardiopulmonary exercise test and exercise blood pressure measurement were performed. Plasma B-natriuretic peptide (BNP) concentration at rest and at peak exercise, plasma high sensitive-C reaction protein (hs-CRP) and endothelin (ET) concentration were determined at baseline and after treatment. RESULTS: After treatment by atorvastatin, the resting SBP, pulse pressure, the peak exercise SBP and BNP were significantly decreased; and the exercise time, metabolic equivalent, maximal oxygen uptake and anaerobic threshold were increased. All of these parameters had significant differences with baseline levels (P<0.05) and the rest pulse pressure, the peak exercise SBP and BNP, and the exercise time had significant differences compared with placebo treatment (P<0.05). Plasma concentrations of hs-CRP and ET were markedly reduced by atorvastatin treatment compared with baseline and placebo (P<0.05). No difference in above parameters was found before and after placebo treatment (P>0.05). CONCLUSION: In patients with diastolic dysfunction at rest and exercise-induced hypertension, atorvastatin can effectively reduce plasma hs-CRP and ET level, lower blood pressure and peak exercise SBP, decrease peak exercise plasma BNP concentration, and ultimately improve exercise tolerance.


Assuntos
Tolerância ao Exercício/efeitos dos fármacos , Insuficiência Cardíaca/tratamento farmacológico , Ácidos Heptanoicos/farmacologia , Hipertensão/tratamento farmacológico , Pirróis/farmacologia , Idoso , Atorvastatina , Proteína C-Reativa/metabolismo , Método Duplo-Cego , Endotelinas/sangue , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Estudos Prospectivos
11.
Cell Physiol Biochem ; 33(4): 991-1002, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24714122

RESUMO

BACKGROUND: Osteopontin (OPN) is associated with tumor formation, progression and metastasis, and increased OPN levels have been associated with poor survival in breast cancer. We investigated the mechanisms responsible for OPN activity, and the relationships between OPN expression and clinical parameters in breast cancer. METHODS: OPN mRNA and protein levels were compared in malignant and benign breast tumors by polymerase chain reaction (PCR) and immunohistochemistry, respectively, and levels in breast cancer cells were determined by PCR and western blotting. The effects of lentiviral-mediated knockdown of OPN on OPN and αv,ß3 integrin expression, cell invasion and migration, autophagy and apoptosis were analyzed in MDA-MB-231 cells. RESULTS: OPN expression increased with aggressiveness of breast cancer phenotype. OPN knockdown inhibited αv,ß3 integrin expression in MDA-MB-231 cells, with subsequent inhibition of cell migration and invasion. Knockdown also inhibited the PI3K/Akt/mTOR pathway, promoted expression of the autophagy-related gene products LC3 and Beclin 1, and increased apoptosis. OPN expression was positively associated with tumor grade and lymph node metastasis. CONCLUSION: These results suggest that knockdown of OPN may inhibit breast cancer metastasis by regulating αv,ß3 integrin expression and inducing autophagy and subsequent inhibition of PI3K/Akt/mTOR signaling, thus providing further insights into the complex mechanisms regulating tumor growth and metastasis.


Assuntos
Apoptose , Autofagia , Neoplasias da Mama/patologia , Integrina alfaVbeta3/metabolismo , Osteopontina/metabolismo , Transdução de Sinais , Adulto , Idoso , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Feminino , Humanos , Imuno-Histoquímica , Células MCF-7 , Pessoa de Meia-Idade , Osteopontina/antagonistas & inibidores , Osteopontina/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno/metabolismo , Serina-Treonina Quinases TOR/metabolismo
12.
Anal Bioanal Chem ; 406(6): 1693-700, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24458480

RESUMO

A functionalized gold-nanoparticle bio-barcode assay, based on real-time immuno-PCR (IPCR), was designed for the determination of 3,4,3',4'-tetrachlorobiphenyl (PCB77). 15 nm gold nanoparticles were synthesized, and modified with thiol-capped DNA and goat anti-rabbit IgG. The nanoparticle probes were used to replace antibody-DNA conjugate in the IPCR, and were fixed on the PCR tube wall via the immune reaction. Real-time PCR was performed to quantify the DNA signal directly. Under optimized conditions, the new method was used to detect PCB77 with a linearity range from 5 pg L(-1) to 10 ng L(-1), and the limit of detection (LOD) was 1.72 pg L(-1). Real samples of Larimichthys polyactis, collected from the East China Sea, were analyzed. Recovery was from 82 % to 112 %, and the coefficient of variation (CV) was acceptable. The results were compared with GC-ECD, revealing that the method would be acceptable for providing rapid, semi-quantitative, and reliable test results for making environmental decisions.


Assuntos
Monitoramento Ambiental/métodos , Ouro/química , Nanopartículas/química , Bifenilos Policlorados/análise , Reação em Cadeia da Polimerase em Tempo Real/métodos , Poluentes Químicos da Água/análise , Animais , Anticorpos Anti-Idiotípicos/química , Anticorpos Anti-Idiotípicos/imunologia , Anticorpos Imobilizados/química , Anticorpos Imobilizados/imunologia , DNA/química , Imunoensaio/métodos , Imunoglobulina G/imunologia , Imunoadsorventes/química , Limite de Detecção , Perciformes/metabolismo , Coelhos , Sensibilidade e Especificidade , Compostos de Sulfidrila/química
13.
International Eye Science ; (12): 1344-1347, 2014.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-642013

RESUMO

AlM: To explore the different ages of congenital nasolacrimal duct obstruction in infants, take different treatment methods at different times. METHODS:The 87 cases of 102 children were divided into three different age groups: the first group of 25d-3mo of age 21 cases 26 eyes; The second group >3mo-7mo 31 cases 36 eyes;The third group >7-24mo of age 35 cases 40 eyes. For the first group of infants, the implementation of the lacrimal sac nasolacrimal duct massage + eye drops; for the second group of infants, carry lacrimal pressure washing treatment; for the third group of infants, the implementation of the nasolacrimal duct probing treatment. RESULTS: The first group of children through the nasolacrimal duct sac massage + drops tobramycin eye drops treatment unobstructed 12, the cure rate was 46. 2%;The second group of children through pressurized irrigation treatment lacrimal patency by 33, the cure rate was 91. 7%; The third group of children through the nasolacrimal duct probing unobstructed 36 treatment, the cure rate was 90. 0%. The second and third group were better than the first group (χ2=15. 71, P0. 05). CONCLUSlON:lnfants with congenital nasolacrimal duct obstruction should distinguish between ages, taking different treatments, in order to obtain a better therapeutic effect, and lacrimal pressure washing is the preferred way of treating infants with congenital nasolacrimal duct obstruction.

14.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-251704

RESUMO

<p><b>OBJECTIVE</b>To investigate the effect of atorvastatin on exercise tolerance in patients with diastolic dysfunction and exercise-induced hypertension.</p><p><b>METHODS</b>A randomized, double-blind, placebo-controlled prospective study was performed. Sixty patients with diastolic dysfunction (mitral flow velocity E/A <1) and exercise-induced hypertension (SBP>200 mm Hg) treated with atorvastatin (20 mg q.d) or placebo for 1 year. Cardiopulmonary exercise test and exercise blood pressure measurement were performed. Plasma B-natriuretic peptide (BNP) concentration at rest and at peak exercise, plasma high sensitive-C reaction protein (hs-CRP) and endothelin (ET) concentration were determined at baseline and after treatment.</p><p><b>RESULTS</b>After treatment by atorvastatin, the resting SBP, pulse pressure, the peak exercise SBP and BNP were significantly decreased; and the exercise time, metabolic equivalent, maximal oxygen uptake and anaerobic threshold were increased. All of these parameters had significant differences with baseline levels (P<0.05) and the rest pulse pressure, the peak exercise SBP and BNP, and the exercise time had significant differences compared with placebo treatment (P<0.05). Plasma concentrations of hs-CRP and ET were markedly reduced by atorvastatin treatment compared with baseline and placebo (P<0.05). No difference in above parameters was found before and after placebo treatment (P>0.05).</p><p><b>CONCLUSION</b>In patients with diastolic dysfunction at rest and exercise-induced hypertension, atorvastatin can effectively reduce plasma hs-CRP and ET level, lower blood pressure and peak exercise SBP, decrease peak exercise plasma BNP concentration, and ultimately improve exercise tolerance.</p>


Assuntos
Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atorvastatina , Proteína C-Reativa , Metabolismo , Método Duplo-Cego , Endotelinas , Sangue , Tolerância ao Exercício , Insuficiência Cardíaca , Tratamento Farmacológico , Ácidos Heptanoicos , Farmacologia , Hipertensão , Tratamento Farmacológico , Peptídeo Natriurético Encefálico , Sangue , Estudos Prospectivos , Pirróis , Farmacologia
15.
Toxicol Lett ; 218(2): 129-36, 2013 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-23164673

RESUMO

Cinobufagin, a major component of cinobufacini (huachansu), is an important cardenolidal steroid. Several studies have suggested that cinobufagin has potent anti-cancer effects. The present study examines the apoptosis-inducing activity and the underlying mechanism of action of cinobufagin in osteosarcoma (OS) cells. Our results showed that cinobufagin potently inhibited the proliferation of U2OS, MG63 and SaOS-2 cells. Significant increases in G2/M cell-cycle arrest and apoptosis in OS cells were also observed. The expression levels of several apoptotic proteins were assessed after cinobufagin treatment in U2OS cells. Among them, xIAP, cIAP-1, survivin and Bcl-2 levels decreased remarkably, while the levels of Bax and cleaved-PARP increased. Furthermore, we validated the inhibition of GSK-3ß/NF-κB signaling following cinobufagin treatment. Western blots showed a decrease in nuclear p65 protein expression after exposure to different concentrations of cinobufagin, while the phosphorylation of GSK-3ß was simultaneously increased. Transduction with constitutively active forms of GSK-3ß could protect against the downregulation of p65 and upregulation of cleaved-PARP that are induced by cinobufagin treatment. However, combined treatment with cinobufagin and SB216367 resulted in a significant reduction in p65 and an increase in cleaved-PARP in U2OS cells. Altogether, these results show that cinobufagin is a promising agent for the treatment of OS. These studies are the first to reveal the involvement of the GSK-3ß/NF-κB pathway in cinobufagin-induced apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Bufanolídeos/farmacologia , Quinase 3 da Glicogênio Sintase/metabolismo , NF-kappa B/metabolismo , Venenos de Anfíbios/análise , Venenos de Anfíbios/química , Antineoplásicos/farmacologia , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo , Quinase 3 da Glicogênio Sintase/genética , Glicogênio Sintase Quinase 3 beta , Humanos , NF-kappa B/genética , Osteossarcoma/metabolismo , Fosforilação , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo , Transdução de Sinais , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Transfecção , Regulação para Cima
16.
Zhonghua Wai Ke Za Zhi ; 50(2): 135-8, 2012 Feb 01.
Artigo em Chinês | MEDLINE | ID: mdl-22490352

RESUMO

OBJECTIVE: To determine the effects of modified pull-through operation (Badenoch operation) on the treatment of posterior urethral stricture. METHODS: From September 2001 to December 2010 traditional pull-through operation was Modified for two times in our center. A total of 129 patients with posttraumatic posterior urethral stricture resulting from pelvic fracture injury underwent the modified urethral pull-through operation. Stricture length was 1.5 to 5.3 cm (mean 2.9 cm). Of the patients 43 had undergone at least 1 previous failed management for stricture. In phase 1 (from September 2001 to January 2008), the improving items include: (1) The distal urethral end was stitched and tied to the catheter. (2) As catheter was inserted into bladder and 20 ml water was injected into catheter balloon, the distal urethral end was fixed in the proximal urethra and an overlaying of 1.5 cm was formed between the two ends. (3) Three weeks later, it was tried to insert the catheter to bladder. After the urethral stump necrosis and the catheter separating from the urethra, the catheter was removed. In phase 2 (from February 2008 to December 2010), based on the above, irrigating catheter was used. After the surgery, urethra was irrigated with 0.02% furacillin solution through the catheter 3 times a day. All patients were followed up for at least 6 months. If patients had no conscious dysuria and maximum urinary flow rate (Qmax) > 15 ml/s, the treatment was considered successful. All complications were recorded. RESULTS: In phase 1, the 96 patients (101 times) underwent the procedure. The treatment was successful in 88 patients (success rate 92%). Within 1 to 13 days after removal of the catheter, urethral stricture was recurred in 8 patients. They had to undergo cystostomy once more for 3 to 11 months before reoperation (the 3 patients' reoperation was in phase 2). The 8 cases were treated successfully. In phase 2, 33 patients (total 36 times) underwent the procedure. One patient was failed (success rate 97%). The actual follow-up time is 7 to 93 months (An average of 37.6 months). Qmax is (22 ± 5) ml/s. No complications such as urinary incontinence, erectile pain, urinary shortening happened. CONCLUSIONS: The modified urethral pull-through operation is effective for the surgical treatment of posttraumatic posterior urethral stricture. It has a high success rate with durable long-term results. Complications are few. The procedure is simple, less demanding and especially suitable in patients who had previously undergone failed surgical treatments.


Assuntos
Uretra/cirurgia , Estreitamento Uretral/cirurgia , Adulto , Idoso , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
17.
World J Surg ; 36(2): 468-72, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21882021

RESUMO

BACKGROUND: During living-donor kidney transplantation, to maximally decrease donor injury, the right kidney with lower glomerular filtration rate often is selected as the donor kidney. However, the renal vein of the right kidney is relatively short for transplantation. The gonadal vein is essentially useless and is easily accessed during the donor nephrectomy. METHODS: Seventeen live kidney donors received right kidney nephrectomy for living-donor kidney transplantation. Short renal veins were lengthened by circular anastomosis or spiral anastomosis of longitudinally cut gonadal veins. The renal function of receivers was evaluated using creatinine clearance. RESULTS: The renal veins were extended by 2.0-2.7 cm with circular anastomosis and 4.1-4.5 cm with spiral anastomosis with an average of 2.5 ± 0.7 cm. Lengthening of renal veins averaged 20.4 ± 4.2 min. All surgeries were successful, significantly reducing difficulty of vascular anastomosis during transplantation. No poor early graft function occurred. No side effects were observed in donors. CONCLUSIONS: When donor renal veins are too short for effective kidney transplantation and may affect reliability of vascular anastomosis, they can be lengthened by using gonadal veins without increasing injury to the donor. Successful extension of donor kidney renal veins expands the indication for right donor kidneys.


Assuntos
Transplante de Rim , Doadores Vivos , Nefrectomia/métodos , Veias Renais/transplante , Adulto , Anastomose Cirúrgica , Feminino , Laparoscopia Assistida com a Mão , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Prospectivos , Veias Renais/cirurgia , Ureter/irrigação sanguínea
18.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-635565

RESUMO

Microbial keratitis is one of major causes of vision loss and blindness worldwide today,especially in developing countries in Asia and Africa.Population-based annual incidence of microbial keratitis is 0.36/10000 to 79.9 /104.The epidemiological features and predisposing factors for microbial keratitis varies significantly from country to country,even from region to region within the same country.The progress of research on describing epidemiological characteristics demographiccharacteristics andpredisposing factors of microbialkeratitiswere reviewed in this paper.

19.
Chinese Journal of Surgery ; (12): 135-138, 2012.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-257539

RESUMO

<p><b>OBJECTIVE</b>To determine the effects of modified pull-through operation (Badenoch operation) on the treatment of posterior urethral stricture.</p><p><b>METHODS</b>From September 2001 to December 2010 traditional pull-through operation was Modified for two times in our center. A total of 129 patients with posttraumatic posterior urethral stricture resulting from pelvic fracture injury underwent the modified urethral pull-through operation. Stricture length was 1.5 to 5.3 cm (mean 2.9 cm). Of the patients 43 had undergone at least 1 previous failed management for stricture. In phase 1 (from September 2001 to January 2008), the improving items include: (1) The distal urethral end was stitched and tied to the catheter. (2) As catheter was inserted into bladder and 20 ml water was injected into catheter balloon, the distal urethral end was fixed in the proximal urethra and an overlaying of 1.5 cm was formed between the two ends. (3) Three weeks later, it was tried to insert the catheter to bladder. After the urethral stump necrosis and the catheter separating from the urethra, the catheter was removed. In phase 2 (from February 2008 to December 2010), based on the above, irrigating catheter was used. After the surgery, urethra was irrigated with 0.02% furacillin solution through the catheter 3 times a day. All patients were followed up for at least 6 months. If patients had no conscious dysuria and maximum urinary flow rate (Qmax) > 15 ml/s, the treatment was considered successful. All complications were recorded.</p><p><b>RESULTS</b>In phase 1, the 96 patients (101 times) underwent the procedure. The treatment was successful in 88 patients (success rate 92%). Within 1 to 13 days after removal of the catheter, urethral stricture was recurred in 8 patients. They had to undergo cystostomy once more for 3 to 11 months before reoperation (the 3 patients' reoperation was in phase 2). The 8 cases were treated successfully. In phase 2, 33 patients (total 36 times) underwent the procedure. One patient was failed (success rate 97%). The actual follow-up time is 7 to 93 months (An average of 37.6 months). Qmax is (22 ± 5) ml/s. No complications such as urinary incontinence, erectile pain, urinary shortening happened.</p><p><b>CONCLUSIONS</b>The modified urethral pull-through operation is effective for the surgical treatment of posttraumatic posterior urethral stricture. It has a high success rate with durable long-term results. Complications are few. The procedure is simple, less demanding and especially suitable in patients who had previously undergone failed surgical treatments.</p>


Assuntos
Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Seguimentos , Resultado do Tratamento , Uretra , Cirurgia Geral , Estreitamento Uretral , Cirurgia Geral
20.
Zhongguo Gu Shang ; 24(8): 667-71, 2011 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-21928674

RESUMO

OBJECTIVE: To investigate the therapeutic effects of closed reduction and external fixation (plaster or splint) for the treatment of displaced humeral supracondylar fractures in children. METHODS: From March 2007 to September 2009,33 children (15 female and 18 male) with humeral supracondylar fractures treated in our hospital, ranging from 3 to 12 years old with an average of 6.4 years old. All the fractures were extension-type injuries, the flexion injures were excluded in our study. The humeral supracondylar fractures were classified according to Gartland classification. There were 21 Type H and 12 type III. In the initial treatment, all the patients were treated with closed reduction and external immobilization. The blood supply of the damaged upper extremity was evaluated before and after treatment. Clinical assessment was obtained at final follow-up using Flynn criteria, and radiologic assessment was obtained using Baumann and lateral humerocapitellar angles. RESULTS: All the children were treated successfully with closed reduction in the initial time; 24 children maintained limb alignment by external immobilization. Nine patients lost position due to the swelling around the elbow which affected unstable external fixation during the follow-up, 5 of which were treated with a repeated closed reduction and internal fixation with Kirschner wires, 4 of which were treated with traction. Thirty-one patients had a satisfactory outcome and 2 patients had an unsatisfactory outcome according to the Flynn criteria at the latest follows-up. CONCLUSION: Closed reduction and external stabilization is an important method for the treatment of displaced humeral supracondylar fractures in children. Making regular follow-up visits after closed reduction and casting is important for patients to maintain acceptable alignment, avoid complications and diagnose any loss of reduction.


Assuntos
Moldes Cirúrgicos , Fixadores Externos , Fraturas do Úmero/cirurgia , Contenções , Criança , Pré-Escolar , Feminino , Fixação Interna de Fraturas , Humanos , Masculino
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