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1.
Biomed Chromatogr ; 34(2): e4735, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31691999

RESUMO

The biosynthesis of sialic acid (Neu5Ac) leads to the intracellular production of cytidine-5'-monophospho-N-acetylneuraminic acid (CMP-Neu5Ac), the active sialic acid donor to nascent glycans (glycoproteins and glycolipids) in the Golgi. UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase myopathy is a rare autosomal recessive muscular disease characterized by progressive muscle weakness and atrophy. To quantify the intracellular levels of CMP-Neu5Ac as well as N-acetylmannosamine (ManNAc) and Neu5Ac in human leukocytes, we developed and validated robust liquid chromatography-tandem mass spectrometry methods. A fit-for-purpose approach was implemented for method validation. Hydrophilic interaction chromatography was used to retain three hydrophilic analytes. The human leukocyte pellets were lysed and extracted in a methanol-water mixture and the leukocyte extract was used for LC-MS/MS analysis. The lower limits of quantitation for ManNAc, Neu5Ac and CMP-Neu5Ac were 25.0, 25.0 and 10.0 ng/ml, respectively. These validated methods were applied to a clinical study.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31454555

RESUMO

BACKGROUND: This research was designed to investigate patient-reported and doctor-reported reasons for the discontinuation of pharmacological treatment in Chinese patients with major depressive disorder (MDD), which was part of the National Survey on Symptomatology of Depression (NSSD) from 2014 to 2015. METHODS: This cross-sectional study included 649 patients who had discontinued antidepressant medications and 711 patients who had remained on them, selected from a group of 3516 candidates who have had at least one depressive episode. Differences in the two groups' sociodemographic factors, clinical characteristics, medication use, and self-reported reasons for drug discontinuation were compared via Student's t-test or chi-square test. Logistic regression analysis was then used to determine the association of all non-subjective dichotomous and ordinal categorical variables, including the additional 63 items of our physician-evaluated symptomatic assessment, with drug compliance. RESULTS: Compared to the spontaneous drug discontinuation (SDD) group, the drug adherence (DA) group had significantly lower rates of the following: family history of mental disease (9.0% vs 13.6%), highest level of education achieved being post-graduate or above (1.6% vs 4.7%), smoking (5.8% vs 9.7%), and other health problems (33.9% vs 42.4%) (p's < 0.05). On the other hand, first-episode depression (48.5% vs 21.9%) and taking of mood stabilizer(s) (8.3% vs 5.6%) were higher in the former group than in the latter (p's < 0.05). Logistic Regression Analysis showed that five symptoms, such as depressed mood, were correlated positively with SDD, while another six symptoms, such as psychomotor retardation, were correlated negatively with it. The receiver operating characteristic (ROC) curve of this model yielded an area under the curve (AUC) of 0.701 (95% CI, 0.673-0.729). Notably, there were three main reasons given by patients in the DA group as to why they discontinued their medication(s): (1) concern about long-term side effects (36.1%), (2) no perceived need for taking said medication(s) long-term (34.2%), and (3) believing oneself to have been cured completely (30.0%). CONCLUSIONS: The aforementioned factors may affect patient compliance and elicit maladaptive thinking even from patients with good educational backgrounds, increasing the risk of drug discontinuation. Compliance of pharmacological treatment might be improved by increasing clarification and elucidation of different symptom clusters to the patient and combating the main reasons for drug discontinuation.

3.
Ann Transl Med ; 7(16): 383, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31555697

RESUMO

Background: Familial focal segmental glomerulosclerosis (fFSGS) is difficult to treat, and stem cell transplantation is one of the most promising approaches for treating this condition. According to the novel mutation site found in our FSGS family, we established a novel animal model of FSGS to explore the application of stem cell therapy in FSGS. Methods: The animal model used in this experiment was p.Gly1617Valfs X15 (C57BL/6) mutant mice. This mutation was first found in a focal segmental glomerulosclerosis (FSGS) family undergoing renal biopsy in our department. The mouse model was then constructed via CRISPR/Cas9 genomic editing technology. Then, the animals were injected with human umbilical cord mesenchymal stem cells (UCMSC) through the tail vein and regularly followed up to determine phenotypic changes in urine protein quantities, serum creatinine and histological outcomes. Results: Compared with the positive control group, the levels of urinary protein and serum creatine were decreased significantly after UCMSC transplantation. HE staining images revealed a delay in glomerular sclerosis. Moreover, the secretion of the type IV collagen α3 chain was significantly increased compared with the positive control group, as shown by using immunofluorescence microscopic observation, and electron microscopy proved that the podocytes and basement membrane recovered well from the damage. The intervention also resulted in enhanced IL-22 expression. Conclusions: UCMSC transplantation may be a potential treatment for FSGS, and IL-22 may play an important role in this process. Further studies are needed to reveal the underlying mechanism.

4.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(2): 179-182, 2019 Feb 10.
Artigo em Chinês | MEDLINE | ID: mdl-30703243

RESUMO

Type IV collagen is a component of the extracellular matrix in the basement membrane. Abnormal secretion or assembly of type IV collagen may lead to kidney lesions resulting in numerous nephropathy symptoms, e.g., Alport syndrome, thin basement membrane nephropathy, and focal segmental glomerulosclerosis. Treatment for type IV collagen-related nephropathy includes drugs, kidney transplantation, gene and cell therapy. However, drugs are not always effective, and kidney transplantation is hindered by the shortage of donors. Moreover, basement membrane nephritis often occurs after kidney transplantation. Therefore, gene and cell therapy probably is the most promising treatment for type IV collagen related nephropathies.


Assuntos
Glomerulosclerose Segmentar e Focal , Nefrite Hereditária , Terapia Baseada em Transplante de Células e Tecidos , Colágeno Tipo IV , Hematúria , Humanos
5.
Clin Infect Dis ; 67(suppl_2): S249-S255, 2018 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-30423040

RESUMO

Background: Vancomycin is a first-line antibiotic used for the treatment of severe gram-positive bacterial infections. Clinical guidelines recommend that the vancomycin trough concentration be 10-15 mg/L for regular infections and 15-20 mg/L for severe infections. We investigated whether increasing the vancomycin concentration would result in better clinical outcomes with sustainable adverse effects (AEs) in the Chinese population. Methods: A prospective, open, multicenter clinical observational study was performed in patients with gram-positive bacterial infections from 13 teaching hospitals. Patients received vancomycin therapeutic drug monitoring. Clinical, microbiological, and laboratory data were collected. Results: In total, 510 patients were enrolled, and 470 were evaluable, of whom 370 were adults and 100 were children; 35.53% had methicillin-resistant Staphylococcus aureus infections (vancomycin 50% minimum inhibitory concentration [MIC50] = 1, 90% minimum inhibitory concentration [MIC90] = 1), and 23.19% had Enterococcus species infections (vancomycin MIC50 = 1, MIC90 = 2). The average trough concentration was 10.54 ± 8.08 mg/L in adults and 6.74 ± 8.93 mg/L in children. The infection was eradicated in 86.22% of adults and 96% of children. Thirty-six vancomycin-related nephrotoxicity cases were reported in the enrolled population. No severe AEs or deaths were related to vancomycin therapy. Logistic regression analysis showed that trough concentration had no relationship with clinical outcomes (adults P = .75, children P = .68) but was correlated with adult nephrotoxicity (P < .0001). Vancomycin trough concentration had an applicable cut point at 13 mg/L. Conclusions: Our study shows that vancomycin trough concentration has no statistical correlation with clinical outcomes, and is an indicator of nephrotoxicity in the observed population. We found no evidence that increasing vancomycin trough concentration to 15-20 mg/L can benefit Chinese patients with complicated infections. Clinical Trials Registration: ChiCTR-OPC-16007920.


Assuntos
Antibacterianos/uso terapêutico , Monitoramento de Medicamentos , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Vancomicina/uso terapêutico , Adolescente , Idoso , Criança , Pré-Escolar , China , Relação Dose-Resposta a Droga , Feminino , Hospitais de Ensino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
6.
Nephrology (Carlton) ; 23 Suppl 4: 57-61, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30298667

RESUMO

Focal segmental glomerulosclerosis (FSGS) is a glomerulonephritis with podocyte injury. The renal prognosis of FSGS is relative poor. The overall remission rate of the FSGS patients with nephrotic syndrome to immunosuppressive treatments was reported as 47-66%, highlighting its therapeutic challenge-lacking in sufficient evidence-based interventions. In first-line treatment of nephrotic syndrome, daily oral prednisolone is a commonly used drug, whereas optimal treatment strategies, like indications and duration, remain controversial. Calcineurin inhibitor and cyclophosphamide are recommended in steroid-dependent/steroid-resistant patients. However, the high unmet need in effective immunosuppressive treatments calls for the development of new therapy methods. Rituximab, a monoclonal antibody targeting CD20 B-cells, could increase the complete or partial remission rate, and decrease the relapse rate based on several previous studies on FSGS. In addition, the using of rituximab could potentially help the FSGS patients to stop the concomitant therapy include steroid and immunosuppressive agents. Other treatment options like adalimumab or abatacept also showed potential therapeutic effect, but still required larger Randomized Controlled Trial study to determine its efficiency and safety. Besides, expanding understanding of the genetic basis of FSGS is necessary to investigate new therapeutic agents. With the unsatisfied patients' outcome under the current treatments, innovation should be encouraged on the treatment strategy based on Kidney Disease: Improving Global Outcomes guideline and international collaborations are required for the potential novel immunosuppressive or immunomodulatory therapies.


Assuntos
Corticosteroides/uso terapêutico , Produtos Biológicos/uso terapêutico , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Imunossupressores/uso terapêutico , Glomérulos Renais/efeitos dos fármacos , Corticosteroides/efeitos adversos , Produtos Biológicos/efeitos adversos , Tomada de Decisão Clínica , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulosclerose Segmentar e Focal/imunologia , Humanos , Imunossupressores/efeitos adversos , Glomérulos Renais/imunologia , Glomérulos Renais/patologia , Recidiva , Indução de Remissão , Fatores de Risco , Resultado do Tratamento
7.
Sci Rep ; 8(1): 10066, 2018 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-29968814

RESUMO

Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) provides three-dimensional information on aerosol optical properties across the globe. However, the performance of CALIPSO aerosol optical depth (AOD) products under different air quality conditions remains unclear. In this research, three years of CALIPSO level 2 AOD data (November 2013 to December 2017) were employed to compare with the Moderate Resolution Imaging Spectroradiometer (MODIS) level 2 columnar AOD products and ground-based sun photometer measurements for the same time period. To investigate the effect of air quality on AODs retrieved from CALIPSO, the AODs obtained from CALIPSO, MODIS, and sun photometer were inter-compared under different air quality conditions over Wuhan and Dengfeng. The average absolute bias of AOD between CALIPSO and sun photometer was 0.22 ± 0.21, 0.11 ± 0.07, and 0.14 ± 0.13 under clean, moderate, and polluted weather, respectively. The result indicates that the CALIPSO AOD were more reliable under moderate and polluted days. Moreover, the deviation of AOD between CALIPSO and sun photometer was largest (0.23 ± 0.21) in the autumn season, and lowest (0.13 ± 0.12) in the winter season. The results show that CALIPSO AOD products were more applicable to regions and seasons with high aerosol concentrations.

8.
Huan Jing Ke Xue ; 39(7): 3033-3041, 2018 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-29962123

RESUMO

In this study, PM2.5 samples were collected from October to November of 2015 in the northern suburb of Nanjing. The mass concentrations of organic carbon (OC), elemental carbon (EC), and levoglucosan in the samples were analyzed by thermal optical transmittance (TOT) and ion chromatography. The average concentrations of OC and EC were respectively (11.3±4.9) µg·m-3 and (1.1±0.9) µg·m-3. The average total carbon (TC) was 22.9%, and the OC/EC was 7.4. The quality concentrations of PM2.5, OC, EC, and SOC all reflected daytime features, and the correlation between OC and EC was better during the day than at night (correlation coefficients of 0.86 for day and 0.7 for night). By analyzing the mass concentrations of PM2.5, levoglucosan, and SOC, as well as the data of backward trajectories and fire point data, it was determined that the northern suburb of Nanjing is affected by the long-distance transportation of biomass from Hebei and other places from October 13-16. The correlations between levoglucosan and OC, EC, or SOC were significant (correlation coefficients of 0.78, 0.79, and 0.65, respectively), and the contribution of biomass combustion during sampling to OC was 21.9%.

9.
Artigo em Inglês | MEDLINE | ID: mdl-29883889

RESUMO

Sulprostone is a potent prostaglandin E2 (PGE2) analogue and one of the first identified selective G-protein-coupled receptor 3 (EP3) agonists. It has been investigated as a potential antiulcer agent and frequently used in the research of EP3 antagonist. To assist pharmacokinetic and pharmacodynamic studies, a rapid and sensitive LC-MS/MS method was developed and qualified for the quantitation of sulprostone in monkey plasma. Using electrospray ionization mass spectrometry, an ammonium adduct in positive mode was chosen for analysis which had seven times of the sensitivity of the depronated ion in negative mode. Latanoprost, a prostaglandin F2α analogue, was used as the internal standard while good sensitivity and chromatography were obtained on a 2.6 µm core-shell column with pentafluorophenyl stationary phase. An assay dynamic range of 2 to 4000 ng/mL was achieved with a sample volume of 25 µL plasma on a Sciex API4000 instrument with simple protein precipitation. Several esterase inhibitors including sodium fluoride (NaF), phenylmethanesulfonyl fluoride (PMSF), diisopropylfluorophosphate (DFP), paraoxon and dichlorvos as well as wet ice conditions were explored for the stabilization of sulprostone in monkey plasma. The developed method was successfully applied for the evaluation of pharmacokinetics of sulprostone after intravenous administration of 0.5 mg/kg to cynomolgus monkey.


Assuntos
Cromatografia Líquida/métodos , Dinoprostona/análogos & derivados , Espectrometria de Massas em Tandem/métodos , Animais , Dinoprostona/sangue , Dinoprostona/química , Dinoprostona/farmacocinética , Estabilidade de Medicamentos , Modelos Lineares , Macaca fascicularis , Masculino , Receptores de Prostaglandina E Subtipo EP3/agonistas , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
10.
IEEE Trans Cybern ; 2018 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-30596592

RESUMO

Clustering ensemble (CE) takes multiple clustering solutions into consideration in order to effectively improve the accuracy and robustness of the final result. To reduce redundancy as well as noise, a CE selection (CES) step is added to further enhance performance. Quality and diversity are two important metrics of CES. However, most of the CES strategies adopt heuristic selection methods or a threshold parameter setting to achieve tradeoff between quality and diversity. In this paper, we propose a transfer CES (TCES) algorithm which makes use of the relationship between quality and diversity in a source dataset, and transfers it into a target dataset based on three objective functions. Furthermore, a multiobjective self-evolutionary process is designed to optimize these three objective functions. Finally, we construct a transfer CE framework (TCE-TCES) based on TCES to obtain better clustering results. The experimental results on 12 transfer clustering tasks obtained from the 20newsgroups dataset show that TCE-TCES can find a better tradeoff between quality and diversity, as well as obtaining more desirable clustering results.

11.
BMC Pregnancy Childbirth ; 17(1): 393, 2017 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-29169330

RESUMO

BACKGROUND: To investigate the differences in cardiovascular disease, extracardiac anomalies and outcomes between fetuses with levocardia and dextrocardia. METHODS: Clinical demographics, prenatal features, postnatal characteristics and the outcomes of fetuses with levocardia or dextrocardia were recorded and analyzed. RESULTS: Sixty-five fetuses with dextrocardia and thirty-eight fetuses with levocardia were enrolled. Right ventricle outlet obstruction, atrioventricular septal defect and intestinal malrotation were common in both groups. Univentricular physiology, transposition of the great arteries and esophageal atresia were more frequent in fetuses with levocardia, whereas abnormal pulmonary venous connection, double outlet of right ventricle, left ventricle outlet obstruction and brain abnormalities were more frequent in the dextrocardia group. The accuracy of evaluating cardiac malformations was high, but the sensitivity in assessing extracardiac abnormalities was low. CONCLUSIONS: Although the disorders have certain overlapping features, there are several differences between fetuses with levocardia and dextrocardia. These findings might improve patient counseling and perinatal management.


Assuntos
Anormalidades Múltiplas/fisiopatologia , Dextrocardia/fisiopatologia , Coração Fetal/fisiopatologia , Síndrome de Heterotaxia/fisiopatologia , Levocardia/fisiopatologia , Anormalidades Múltiplas/embriologia , Adulto , Dextrocardia/embriologia , Dextrocardia/etiologia , Feminino , Defeitos dos Septos Cardíacos/embriologia , Ventrículos do Coração/anormalidades , Ventrículos do Coração/embriologia , Síndrome de Heterotaxia/complicações , Síndrome de Heterotaxia/embriologia , Humanos , Levocardia/embriologia , Levocardia/etiologia , Gravidez , Veias Pulmonares/anormalidades , Veias Pulmonares/embriologia , Transposição dos Grandes Vasos/embriologia , Função Ventricular
12.
Anal Chem ; 89(16): 8399-8404, 2017 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-28696683

RESUMO

The following work describes a combined enzymatic and bioanalytical method that permits absolute quantitation of metabolites in biological samples without the requirement for reference metabolite standards. This technique was exemplified using a radio (14C) isotopologue and a stable (13C6) isotopologue of acetaminophen as substrates for in vitro biosynthesis of the corresponding radio and stable isotope labeled metabolites, namely, 14C- and 13C6-glucuronides and sulfates. By supplanting the use of authentic metabolite standards, traditionally used to calibrate 13C6-metabolites via liquid chromatography-tandem mass spectrometry (LC-MS/MS), 13C6-metabolites were radiocalibrated by their 14C-isotopologues via liquid chromatography coupled with radioactivity detection and mass spectrometry (LC-RAD/MS). The radiocalibrated 13C6-isotopologues were in turn used to quantitate acetaminophen and its corresponding metabolites in rat plasma samples by LC-MS/MS. Variation between this and a conventional LC-MS/MS method using authentic standards for calibration was within ±17%, permitting its use in preclinical and clinical applications. Since authentic metabolite standards are not required under the concept of radio and stable isotopologues using adapted LC-RAD/MS protocols, significantly fewer resources are required to support accurate metabolite quantitation which in turn enables efficient analysis of simple and complex metabolite profiles.


Assuntos
Acetaminofen/sangue , Analgésicos não Entorpecentes/sangue , Glucuronídeos/química , Marcação por Isótopo , Sulfatos/química , Acetaminofen/administração & dosagem , Acetaminofen/metabolismo , Administração Oral , Analgésicos não Entorpecentes/administração & dosagem , Analgésicos não Entorpecentes/metabolismo , Animais , Isótopos de Carbono , Radioisótopos de Carbono , Cromatografia Líquida , Glucuronídeos/metabolismo , Masculino , Espectrometria de Massas , Estrutura Molecular , Ratos , Ratos Sprague-Dawley , Sulfatos/metabolismo
13.
Echocardiography ; 34(5): 779-781, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28299808

RESUMO

Pneumopericardium is a rare clinical entity which is often complicated by trauma. Pneumoperdicardium resulting after esophagopericardial fistula is much rarer. We present a case of pneumopericardium as the complication of esophagopericardial fistula in a 53-year-old man. After undergoing radiotherapy for 26 times, the patient got a fever and an unspecified thoracic pain. Echocardiography showed the rectilinear echoes in the pericardium. Chest computed tomography revealed pneumopericardium, pericardial effusion, recurrence of lung cancer, and pneumonia in right lower and left lung.


Assuntos
Fístula Esofágica/complicações , Fístula Esofágica/diagnóstico por imagem , Cardiopatias/complicações , Cardiopatias/diagnóstico por imagem , Pneumopericárdio/diagnóstico por imagem , Pneumopericárdio/etiologia , Diagnóstico Diferencial , Ecocardiografia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Pneumopericárdio/terapia , Doenças Raras/diagnóstico por imagem , Doenças Raras/etiologia , Tomografia Computadorizada por Raios X/métodos
14.
Biomed Chromatogr ; 30(12): 1984-1991, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27245274

RESUMO

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of GDC-0425 concentrations in human plasma has been developed and validated. Supported liquid extraction was used to extract plasma samples (50 µL) and the resulting samples were analyzed using reverse-phase chromatography and mass spectrometry coupled with a turbo-ionspray interface. The mass analysis of GDC-0425 was performed using multiple reaction monitoring transitions in positive ionization mode. The method was validated over the calibration curve range of 1.00-1000 ng/mL using linear regression and 1/x2 weighting. Within-run relative standard deviation ranged from 0.8 to 5.1%, while between-run RSD varied from 1.9 to 4.7% for QCs. The accuracy ranged from 90.0 to 101.0% of nominal for within-run and from 94.0 to 100.0% of nominal for between-run. Overall extraction recovery was 87.4% for GDC-0425 and 87.9% for GDC-0425-d9 . Stability of GDC-0425 was established in human plasma for 374 days at -20 and -70 °C and established in reconstituted sample extracts for 88 h when stored at 2-8 °C. Stable-labeled internal standard was used to minimize matrix effects. This assay was used to characterize the pharmacokinetics of GDC-0425 in cancer patients.


Assuntos
Quinase 1 do Ponto de Checagem/antagonistas & inibidores , Cromatografia Líquida/métodos , Compostos Heterocíclicos com 3 Anéis/sangue , Piperidinas/sangue , Inibidores de Proteínas Quinases/sangue , Espectrometria de Massas em Tandem/métodos , Hemólise , Compostos Heterocíclicos com 3 Anéis/farmacocinética , Humanos , Limite de Detecção , Piperidinas/farmacocinética , Padrões de Referência , Reprodutibilidade dos Testes
15.
Zhonghua Wai Ke Za Zhi ; 54(1): 13-20, 2016 Jan 01.
Artigo em Chinês | MEDLINE | ID: mdl-26792347

RESUMO

OBJECTIVE: To investigate the safety, effectiveness and long-term results of Jinling procedure. METHODS: A total of 1 100 patients with refractory constipation were admitted to the Institute of General Surgery between February 2000 and December 2013 and received Jinling procedure. There were 217 male and 883 female patients with an average age of (45±15) years and an average duration of (275±159) months. The Jinling procedure modifies the classic procedure of subtotal colectomy with colorectal anastomosis by adding a new side-to-side cecorectal anastomosis. The general clinical data, postoperative complications, gastrointestinal quality of life index (GIQLI), Wexner constipation score, satisfaction rate, body composition, nutritional status, homeostasis, anal manometry and defecography during follow-up were collected. Statistical analysis was performed by t-test analysis, χ(2) test or Fisher's exact probability. RESULTS: The postoperative follow-up rate were 96.73%, 94.36%, 93.00% and 92.55% at 1, 3, 6, and 12 months. The satisfaction rate were 62.50%, 72.45%, 93.16% and 94.70% respectively during 1, 3, 6 and 12 months follow-up. The postoperative 1 month, GIQLI was lower than that of preoperative (P=0.038), but significantly better at postoperative 3 month than the preoperative (P=0.022), and gradually improve after then. Wexner score was significantly lower at postoperative 1 month than the preoperative (P=0.018), and with the gradually reduce. Compared to the preoperative baseline, all body composition and serum protein parameters decreased significantly at the one-month follow-up and then increased gradually over the remaining follow-up period. Weight and prealbumin were significantly higher than the preoperative at postoperative 12 month. Jinling procedure had no effect on electrolytes. All patients were detected in defecography before surgery, but these abnormal indicators were improved after surgery. Anal function, coordinated movement anorectal function, anorectal reflex and rectal sensation were injured at early postoperative, but as time goes on, these indicators gradually returned to preoperative levels, some indicators better than the preoperative level. Postoperative surgical site infection, anastomotic bleeding , anastomotic leakage, urinary retention, sexual dysfunction, recurrent constipation, bowel obstruction, anastomotic stricture and mortality rates were 4.36%, 5.45%, 6.00%, 6.91%, 0.64%, 0.45%, 8.82%, 4.00% and 0.27% respectively. CONCLUSIONS: Jinling procedure is a safe and effective surgical procedure for refractory constipation. It can improve defecation function and quality of life significantly, and has a high follow-up satisfaction rate.


Assuntos
Anastomose Cirúrgica , Colectomia , Constipação Intestinal/cirurgia , Adulto , Defecação , Defecografia , Feminino , Seguimentos , Humanos , Obstrução Intestinal , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Qualidade de Vida , Reto , Resultado do Tratamento
16.
Artigo em Inglês | MEDLINE | ID: mdl-26218770

RESUMO

N-acetylneuraminic acid (Neu5Ac or NANA) is the most predominant sialic acid in mammals. As a terminal component in many glycoproteins and glycolipids, sialic acid is believed to be an important biomarker related to various diseases. Its precursor, N-acetylmannosamine (ManNAc), is being investigated as a potential treatment for GNE myopathy. In this work, we developed two highly sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods for the quantitation of ManNAc and free Neu5Ac in human plasma. A fit-for-purpose approach was adopted during method validation and sample analysis. To measure the endogenous compounds and overcome the interference from plasma samples, a surrogate matrix that contained 5% bovine serum albumin (BSA) was used for the preparation of calibration standards and certain levels of quality control (QC) samples. QC samples at higher concentrations were prepared in the authentic matrix (human plasma) to best mimic incurred samples. For both methods, an Ostro 96-well phospholipid removal plate was used for sample extraction, which efficiently removed the phospholipids from the plasma samples prior to LC injection, eliminated matrix effect, and improved sensitivity. Chromatographic separation was achieved using hydrophilic interaction chromatography (HILIC) and gradient elution in order to retain the two polar compounds. The lower limit of quantitation (LLOQ) for ManNAc and Neu5Ac was 10.0 and 25.0ng/mL, respectively. The overall accuracy of the two assays was within 100%±8.3% based on three levels of QC samples. Inter- and intra-run precision (coefficient of variation (%CV)) across three analytical runs was less than 6.7% for ManNAc and less than 10.8% for Neu5Ac. These methods have been validated to support clinical studies.


Assuntos
Cromatografia Líquida/métodos , Hexosaminas/sangue , Ácido N-Acetilneuramínico/sangue , Espectrometria de Massas em Tandem/métodos , Estabilidade de Medicamentos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
17.
J Diabetes Investig ; 4(3): 252-60, 2013 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-24843663

RESUMO

AIMS/INTRODUCTION: Zinc-α2-glycoprotein (ZAG) is associated with the loss of adipose tissue in cancer cachexia, and has recently been proposed to be a candidate factor in the regulation of bodyweight. The aim of the study was to investigate the effects of ZAG on the proliferation and differentiation of 3T3-L1 preadipocytes. MATERIALS AND METHODS: 3-(4,5-Dimethylthiazol-2-yl) 2,5-diphenyl tetrazolium bromide (MTT) spectrophotometry, Oil Red O staining, intracellular triglyceride assays, real-time quantitative reverse transcription polymerase chain reaction and transient transfection methods were used to explore the action of ZAG. RESULTS: Ectopic ZAG expression significantly stimulates 3T3-L1 cells proliferation in a dose- and time-dependent manner. The maximum influence of ZAG on proliferation was 1.43-fold higher than what was observed in control cells. This effect was observed 144 h after transfection with 0.16 µg of murine ZAG (mZAG) plasmid (P < 0.001). The intracellular lipids content in mZAG over-expressing cells were decreased as much as 37% when compared with the control cells after differentiation (P < 0.05, P < 0.01). The messenger ribonucleic acid levels of peroxisome proliferators-activated receptor-γ (PPARγ), CCAAT enhancer-binding protein-α (C/EBPα) and the critical lipogenic gene, fatty acid synthase (FAS), are also downregulated by up to 50% in fully differentiated ZAG-treated adipocytes. ZAG suppresses FAS messenger ribonucleic acid expression by reducing FAS promoter activity. CONCLUSIONS: Zinc-α2-glycoprotein stimulates the proliferation and inhibits the differentiation of 3T3-L1 murine preadipocytes. The inhibitory action of ZAG on cell differentiation might be a result of the attenuation of the expression of PPARγ, C/EBPα and the lipogenic-specific enzyme FAS by reducing FAS promoter activity.

19.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 32(1): 25-8, 2010 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-20236584

RESUMO

OBJECTIVE: To investigate the possible effects and roles of bodyweight on the puberty onset in adolescent girls. METHODS: Totally 288 Chinese female children and adolescent girls aged 5 to 16 were followed up yearly for four consecutive years. The height, bodyweight, fat percentage, sexual characteristics, and the serum levels of leptin and insulin-like growth factor-1 (IGF-1) were studied to analyze the influential factors of puberty onset and age of menarche. RESULTS: The serum level of leptin elevated significantly from age 13 [(9.23 +/- 1.25) microg/L] and reached peak at age 16 [(13.19 +/- 1.45) microg/L]. IGF-1 significantly correlated with the timing of puberty onset (r = 0.292, P = 0.016). BMI and fat percentage had no significant effects on the onset of puberty, but were negatively correlated with the age of menarche (r = -0.323, P = 0.037, r = -0.298, P = 0.038 respectively). CONCLUSION: Bodyweight may have effect on puberty onset in female adolescents.


Assuntos
Desenvolvimento do Adolescente , Peso Corporal , Puberdade/fisiologia , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , Seguimentos , Humanos , Adulto Jovem
20.
Chin Med J (Engl) ; 122(23): 2846-50, 2009 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-20092788

RESUMO

BACKGROUND: Many clinical studies suggest the inverse relationship between testosterone levels and insulin sensitivity in men, however the causative relationship of these two events is still not determined. The purpose of this study was to investigate the effects of testosterone replacement therapy (TRT) on insulin sensitivity, body composition, serum lipid profiles and high sensitivity C-reactive protein (hsCRP) in hypogonadotropic hypogonadal (HH) puberty undeveloped male patients. METHODS: In this prospectively designed study, we compared homeostasis model assessment of insulin resistance (HOMA-IR), insulin areas under the curves (AUC) of 3-hour oral glucose tolerance test (OGTT) and other metabolic parameters between 26 HH patients and 26 healthy men. The patients' HOMA-IR, insulin AUC, body composition, lipid profiles, hsCRP and other parameters were compared before and after nine-month TRT. RESULTS: The average levels of total testosterone (TT) in HH and healthy group were (0.9 +/- 0.6) nmol/L and (18.8 +/- 3.4) nmol/L, respectively. HOMA-IR in HH group was significantly higher than the healthy group (5.14 +/- 5.16 vs 2.00 +/- 1.38, P < 0.005). Insulin AUC in 3-hour OGTT in HH group was significantly higher than the healthy group (698.6 +/- 414.7 vs 414.2 +/- 267.5, P < 0.01). Fasting glucose level in HH group was significantly higher than control group ((5.1 +/- 0.6) mmol/L vs (4.7 +/- 0.3) mmol/l, P < 0.005). Height, weight and grasp strength of the patients were significantly increased after 9-month TRT. Significant reductions in HOMA-IR (from 5.14 +/- 5.16 to 2.97 +/- 2.16, P < 0.01), insulin AUC (from 698.6 +/- 414.7 to 511.7 +/- 253.9, P < 0.01) and hsCRP (from (1.49 +/- 1.18) mg/L to (0.70 +/- 0.56) mg/L, P < 0.05) were found after TRT. Serum total cholesterol, LDL-C, HDL-C and triglyceride were all decreased, albeit with no significant difference compared to the level prior to TRT. CONCLUSIONS: HOMA-IR, insulin AUC and fasting glucose level in HH young male patients were significantly higher than those of the control group, which suggests that low level of testosterone in male adolescents might be a risk factor for insulin resistance. TRT can significantly improve patients' insulin sensitivity and suppress serum hsCRP, which in return suggests that TRT may prevent the HH patients from developing diabetes mellitus and cardiovascular diseases (CVD) in future.


Assuntos
Proteína C-Reativa/análise , Terapia de Reposição Hormonal , Hipogonadismo/tratamento farmacológico , Resistência à Insulina , Testosterona/uso terapêutico , Adolescente , Adulto , Composição Corporal , Humanos , Masculino , Estudos Prospectivos , Puberdade , Adulto Jovem
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