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1.
Org Biomol Chem ; 17(34): 7854-7857, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31408075

RESUMO

A copper-catalyzed DTBP oxidative dual C-H sulfurization has been developed for the direct thiocarbamation of imidazopyridines using a combination of elemental sulfur and formamides as carbamothioyl surrogates. NBS (bromo succinimide) was found to promote the thiocarbamation in good yields. This dual C-H sulfurization strategy enables access to a wide range of carbamothioyl imidazoheterocycles without the use of highly toxic phosgene.

2.
Blood Adv ; 3(14): 2205-2217, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31324641

RESUMO

Anemic stress induces the proliferation of stress erythroid progenitors in the murine spleen that subsequently differentiate to generate erythrocytes to maintain homeostasis. This process relies on the interaction between stress erythroid progenitors and the signals generated in the splenic erythroid niche. In this study, we demonstrate that although growth-differentiation factor 15 (Gdf15) is not required for steady-state erythropoiesis, it plays an essential role in stress erythropoiesis. Gdf15 acts at 2 levels. In the splenic niche, Gdf15-/- mice exhibit defects in the monocyte-derived expansion of the splenic niche, resulting in impaired proliferation of stress erythroid progenitors and production of stress burst forming unit-erythroid cells. Furthermore, Gdf15 signaling maintains the hypoxia-dependent expression of the niche signal, Bmp4, whereas in stress erythroid progenitors, Gdf15 signaling regulates the expression of metabolic enzymes, which contribute to the rapid proliferation of stress erythroid progenitors. Thus, Gdf15 functions as a comprehensive regulator that coordinates the stress erythroid microenvironment with the metabolic status of progenitors to promote stress erythropoiesis.

3.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(2): 256-260, 2019 Apr 28.
Artigo em Chinês | MEDLINE | ID: mdl-31060683

RESUMO

Atherosclerosis-related diseases have increasingly become health concerns with the increased living conditions and aging.Globally,about 200 million people have suffered from arteriosclerosis obliterans(ASO),which can even be life-threatening in some cases.The past seven decades have witnessed the rapid advances in the treatment of ASO,which has developed from surgery to endovascular interventions including plain balloon angioplasty,bare metal stent placement,drug-coated balloon,and drug-eluting stent.However,the roles of these new techniques for femoral-popliteal lesions,especially their real-world clinical outcomes and indications,remain unclear.This article reviews the latest evidences on the use of drug-eluting devices in treating femoral-popliteal arteriosclerosis obliterans.


Assuntos
Arteriosclerose Obliterante/terapia , Stents Farmacológicos/tendências , Angioplastia com Balão , Humanos , Artéria Poplítea/patologia , Stents , Resultado do Tratamento
4.
Parasit Vectors ; 12(1): 221, 2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31068219

RESUMO

BACKGROUND: Protein arginine methylation is a prevalent post-translational modification. The protein arginine methyltransferase family (PRMT) is involved in many cellular processes in eukaryotes, including transcriptional regulation, epigenetic regulation, RNA metabolism, and DNA damage repair. Toxoplasma gondii, an opportunistic protozoan parasite, encodes five conserved PRMTs. PRMT5 is thought to be responsible for substantial PRMT activity in T. gondii; however, it has not yet been characterized. METHODS: We tagged the 3' end of the endogenous TgPRMT5 genomic locus with sequence encoding a 3X hemagglutinin (HA) epitope. IFA and WB were performed to check the expression and subcellular localization of TgPRMT5 in tachyzoites and bradyzoites. In vitro methylation assays were performed to determine whether endogenous TgPRMT5 has arginine methyltransferase activity. RESULTS: IFA and WB results showed that T. gondii PRMT5 (TgPRMT5) was localized in the cytoplasm in the tachyzoite stage; however, it shifts largely to the nuclear compartment in the bradyzoite stage. The in vitro methylation showed that TgPRMT5 has authentic type II PRMT activity and forms monomethylarginines and symmetric dimethylarginines. CONCLUSIONS: We determined the expression and cellular localization of TgPRMT5 in tachyzoites and bradyzoites and confirmed its type II PRMT activity. We demonstrated the major changes in expression and cellular localization of TgPRMT5 during the tachyzoite and bradyzoite stages in T. gondii. Our findings suggest that TgPRMT5 protein may be involved in tachyzoite-bradyzoite transformation.


Assuntos
Proteína-Arginina N-Metiltransferases/genética , Toxoplasma/enzimologia , Toxoplasma/genética , Citoplasma/química , Epigênese Genética , Estágios do Ciclo de Vida , Metilação , Proteína-Arginina N-Metiltransferases/metabolismo
5.
Chin Med J (Engl) ; 132(8): 922-927, 2019 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-30958433

RESUMO

BACKGROUND: In the era of precision medicine, chemotherapy is still considered the cornerstone of treatment for lung cancer patients without gene mutations. How to reduce the toxicity and increase the efficiency of chemotherapy is worth exploring. This study aimed to investigate the curative effects and safety of hyperthermia combined with chemotherapy (HCT) for advanced patients with non-small cell lung cancer (NSCLC), especially those with malignant pleural effusion. METHODS: We retrospectively evaluated medical records of 93 patients with advanced NSCLC (stage IIIB-IV) from March 2011 to January 2014. The patients were divided into HCT and chemotherapy (CT) groups. The HCT group was treated with gemcitabine and cisplatin (GP) regimen combined with regional radiofrequency deep hyperthermia, while the CT group was treated with GP regimen only. Those with malignant pleural effusion extra underwent thoracentesis and intrapleural injection chemotherapy combined with hyperthermic or not. Clinical treatment results and adverse reactions were compared and analyzed after treatment. SPSS 19.0 software (SPSS Inc., USA) was used for statistical data processing. P values less than 0.05 were accepted to be statistically significant. RESULTS: Among the 93 patients, HCT group included 48 patients (16 patients with malignant pleural effusion), CT group included 45 patients (10 patients with malignant pleural effusion). There was no significant difference between the two groups in patient characteristics. The overall response rate (ORR) of pleural effusions was much better in HCT group than that in CT group (81.2% vs. 40.0%, P = 0.046). The patients in HCT group had lower incidence rate of weakness (12.5% vs. 46.7%, χ = 13.16, P < 0.001) and gastrointestinal (25.0% vs. 77.8%, χ = 25.88, P < 0.001) adverse reactions than that in CT group. The objective tumor response and survival showed no significant differences. CONCLUSIONS: Hyperthermia combined with chemotherapy might lead to the development of better therapeutic strategy for advanced NSCLC with malignant pleural effusion patients. Also, it could greatly reduce the chemotherapy toxic effects in the incidence of weakness and gastrointestinal adverse reactions in advanced NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/terapia , Hipertermia Induzida/métodos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/terapia , Adulto , Idoso , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/uso terapêutico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
6.
Org Biomol Chem ; 17(8): 2279-2286, 2019 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-30724304

RESUMO

Dialkyl azo compounds were found to be effective alkyl radical sources for direct alkyl sulfuration with imidazopyridines using elemental sulfur under metal-free conditions. Iodine, an inexpensive and mild reagent, could promote alkyl sulfuration. A variety of quaternary cyanoalkyl radicals were successfully coupled with elemental sulfur. A subsequent C-H sulfuration of imidazopyridines afforded a diverse array of imidazopyridine derivatives bearing cyanoalkylthio groups. The cyano group could be modified and further underwent condensation with 2-aminothiazole to afford an interesting heterocyclic amide. Control experiments showed that iodine could greatly suppress the self-coupling of cyanoalkyl radicals, thus making the sulfuration proceed smoothly.

7.
Methods Mol Biol ; 1893: 75-85, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30565126

RESUMO

Protein-protein interactions provide a common mechanism for regulating protein functions and also serve as the fundamental step of many biochemical reactions. To accurately determine the involvement and function of protein-protein interactions, it is crucial to detect the interactions with the minimum number of artifacts. In this chapter, we report the method of bimolecular fluorescence complementation (BiFC) in tissue culture and developing tissues of Drosophila, which allows the visualization of subcellular localization of protein-protein interactions in living cells.


Assuntos
Drosophila/metabolismo , Imunofluorescência , Imagem Molecular , Mapeamento de Interação de Proteínas , Animais , Linhagem Celular , Drosophila/embriologia , Drosophila/genética , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Expressão Gênica , Humanos , Discos Imaginais , Microscopia de Fluorescência/métodos , Imagem Molecular/métodos , Mapeamento de Interação de Proteínas/métodos , Técnicas de Cultura de Tecidos , Asas de Animais
8.
DNA Cell Biol ; 2018 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-30461308

RESUMO

The considerable amount of experimental evidence has defined the Hippo pathway as a tumor suppressive pathway and increased expression and/or activity of its oncogenic effectors is frequently observed in cancer. However, clinical studies have failed to attribute cancer development and progression to mutations in the pathway. In explaining this conundrum, we investigated the expression and functions of a C-terminally truncated isoform of large tumor suppressor kinase 1 (LATS1) called short LATS1 (sLATS1) in human cell lines and Drosophila. Intriguingly, through overexpression of sLATS1, we demonstrated that sLATS1 either activates or suppresses the activity of Yes-associated protein (YAP), one of the effectors of the Hippo pathway, in a cell type-specific manner. The activation is mediated through inhibition of full-length LATS1, whereas suppression of YAP is accomplished through sLATS1-YAP interaction. In HEK293T cells, the former mechanism may affect the cellular response more dominantly, whereas in U2OS cells and developing tissues in Drosophila, the latter mechanism may be solely carried out. Finally, to find the clinical relevance of this molecule, we examined the expression of sLATS1 in breast cancer patients. The transcriptome analysis showed that the ratio of sLATS1 to LATS1 was increased in tumor tissues comparing to their adjacent normal tissues.

9.
Comput Intell Neurosci ; 2018: 2061516, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30298088

RESUMO

Medical image classification is a key technique of Computer-Aided Diagnosis (CAD) systems. Traditional methods rely mainly on the shape, color, and/or texture features as well as their combinations, most of which are problem-specific and have shown to be complementary in medical images, which leads to a system that lacks the ability to make representations of high-level problem domain concepts and that has poor model generalization ability. Recent deep learning methods provide an effective way to construct an end-to-end model that can compute final classification labels with the raw pixels of medical images. However, due to the high resolution of the medical images and the small dataset size, deep learning models suffer from high computational costs and limitations in the model layers and channels. To solve these problems, in this paper, we propose a deep learning model that integrates Coding Network with Multilayer Perceptron (CNMP), which combines high-level features that are extracted from a deep convolutional neural network and some selected traditional features. The construction of the proposed model includes the following steps. First, we train a deep convolutional neural network as a coding network in a supervised manner, and the result is that it can code the raw pixels of medical images into feature vectors that represent high-level concepts for classification. Second, we extract a set of selected traditional features based on background knowledge of medical images. Finally, we design an efficient model that is based on neural networks to fuse the different feature groups obtained in the first and second step. We evaluate the proposed approach on two benchmark medical image datasets: HIS2828 and ISIC2017. We achieve an overall classification accuracy of 90.1% and 90.2%, respectively, which are higher than the current successful methods.

11.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 40(4): 463-467, 2018 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-30193598

RESUMO

Objective To investigate the change of serum matrix metalloproteinases-9 (MMP-9) expression before,during,and after carotid endarterectomy (CEA) and to investigate the prognostic role of MMP-9. Methods Forty carotid stenosis patients who underwent CEA in the Department of Vascular Surgery,Peking Union Medical College Hospital from February to September 2012 were enrolled in this study. Based on the findings of transcranial doppler monitoring,patients were divided into embolic-positive group and emboli-negative group. Serum samples were obtained from 40 consecutive patients undergoing CEA before operation (pre-op),before de-clamping,30 minutes after de-clamping,and 12 hours after operation (12-h post-op). MMP-9 expression was quantified using enzyme-linked immunosorbent assay and gelatin zymography. Student's t-test and chi-square test were used to compare the differences between these two groups. Results Of these 40 patients,microemboli were detected in 8 patients. The 12-h post-op MMP-9 level was significantly higher than the pre-op level in the emboli-positive group [(904.27±369.47)ng/ml vs. (333.88±126.32) ng/ml,t=4.132,P=0.001].However,there was no difference between pre-op and 12-h post-op MMP-9 levels in the emboli-negative group [(375.83±194.36) ng/ml vs. (472.74±271.21) ng/ml,t=-1.643,P=0.081]. Gelatin zymography also showed higher MMP-9 activity in the emboli-positive group than in the emboli-negative group. Conclusion Serum MMP-9 concentration remarkably increases 12 hours after CEA in patients with microemboli shedding,suggesting MMP-9 may be a potential biomarker for CEA-related cerebral ischemic injury.

12.
Biomed Res Int ; 2018: 8293594, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30046610

RESUMO

Objective: To investigate the effects of electroacupuncture (EA) at "Zusanli" (ST36) and "Shangjuxu"(ST37) on reducing inflammatory reaction and improving intestinal dysfunction in patients with sepsis-induced intestinal dysfunction with syndrome of obstruction of the bowels Qi. Methods: A total of 71 patients with sepsis-induced intestinal dysfunction with syndrome of obstruction of the bowels Qi were randomly assigned to control group (n=36) and treatment group (n=35). Patients in control group were given conventional therapies including fluid resuscitation, anti-infection, vasoactive agents, mechanical ventilation, supply of enteral nutrition, and glutamine as soon as possible. In addition to conventional therapies, patients in treatment group underwent 20 minutes of EA at ST36-ST37 twice a day for five days. At baseline, day 1, day 3, and day 7 after treatment, the plasma levels of procalcitonin (PCT), tumor necrosis factor-α (TNF-α), intestinal fatty acid-binding proteins (I-FABP), D-lactate, citrulline, and TCM quantitative score of intestinal dysfunction were measured and recorded, respectively. And days on mechanical ventilation (MV), length of stay in intensive care unit (ICU), and 28d mortality were recorded. Results: During treatment, the plasma levels of PCT, TNF-α, I-FABP, D-lactate, and TCM quantitative score of intestinal dysfunction were declining in both groups, while the treatment group showed a significant decline (P<0.05). Plasma levels of citrulline were increasing in both groups, while the treatment group showed a significant increase (P<0.05). However, there were no significant differences in the days on MV, length of stay in ICU, and 28d mortality between two groups (P>0.05). Conclusions: EA at ST36-ST37 can reduce inflammatory reaction and has protective effects on intestinal function in patients with sepsis-induced intestinal dysfunction with syndrome of obstruction of the bowels Qi. Trial Registration: This trial was registered at http://www.chictr.org.cn/(ChiCTR-IOR-17010910).

13.
Life Sci ; 207: 381-385, 2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-29924963

RESUMO

AIMS: To determine if tumors located in the subcapsular space or in proximity to vessels would be a risk factor of local tumor progression (LTP2) in hepatocellular carcinomas (HCC) after radiofrequency ablation. MATERIALS AND METHODS: A search of the MEDLINE, EMBASE and Cochrane Library databases from 1998 to 2017 was performed to identify studies examining the risk factors of LTP after radiofrequency ablation (RFA3) in HCC. No language or other restrictions were imposed. Summary estimates of risk factors of LTP were obtained by using a random-effects model with further exploration with meta-regression and sub-group analyses. KEY FINDINGS: There were 16 studies included, of which 7 were focused on the association of LTP with tumors abutting vessels, and 15 focused on tumors of subcapsular location. In total, 2870 patients were included. Tumors that were located in the subcapsular area had a higher occurrence of LTP (P = 0.04) with a high heterogeneity (I2 = 65%), which could not be explained by the results of the meta-regression. However, tumor that were in close to vessels had contrary results (P = 0.54) with a high heterogeneity (I2 = 77%). SIGNIFICANCE: The findings of the present meta-analysis indicate that the subscapsular location is a possible risk factor of LTP. Nevertheless, a clear definition or classification of the subcapsular location should be highlighted in future studies. Whether tumor location adjacent to a vessel has an influence on the incidence of LTP remains controversial, and more relevant research should be performed.


Assuntos
Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/patologia , Idoso , Carcinoma Hepatocelular/metabolismo , Ablação por Cateter , Progressão da Doença , Feminino , Veias Hepáticas/patologia , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Razão de Chances , Veia Porta/patologia , Ondas de Rádio , Reprodutibilidade dos Testes , Projetos de Pesquisa , Fatores de Risco
14.
Medicine (Baltimore) ; 97(17): e0555, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29703040

RESUMO

BACKGROUND: A pathological increase in intraabdominal pressure (IAP) and inflammatory responses have negative effects on splanchnic, respiratory, cardiovascular, renal, and neurological function in septic patients with intestinal dysfunction. Electro-acupuncture (EA) has been evidenced to have a bidirectional neuron-endocrine-immune system regulating effect in patients with intestinal dysfunction. The purpose of current study was to evaluate the effects of EA at "Zusanli" (ST36) and "Shangjuxu" (ST37) on inflammatory responses and IAP in septic patients with intestinal dysfunction manifested syndrome of obstruction of the bowels Qi. METHODS: Eighty-two septic patients with intestinal dysfunction manifested syndrome of obstruction of the bowels Qi were randomly assigned to control group (n = 41) and EA group (n = 41). Patients in control group were given conventional therapies including fluid resuscitation, antiinfection, vasoactive agents, mechanical ventilation (MV), supply of enteral nutrition, and glutamine as soon as possible. In addition to conventional therapies, patients in EA group underwent 20-minutes of EA at ST36-ST37 twice a day for 5 days. At baseline, posttreatment 1, 3, and 7 days, serum levels of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) and IAP levels, were measured, respectively. And days on MV, length of stay in intensive care unit (ICU) and 28 days mortality were recorded. RESULTS: The serum levels of TNF-α and IL-1ß and IAP levels at posttreatment 1, 3, and 7 days were lower significantly in the EA group compared with the control group (mean [SD]; 61.03 [20.39] vs 79.28 [20.69]; P < .005, mean [SD]; 35.34 [18.75] vs 66.53 [30.43]; P < .005 and mean [SD]; 20.32 [11.30] vs 32.99 [20.62]; P = .001, respectively, TNF-α. Mean [SD]; 14.11 [5.21] vs 16.72 [5.59]; P = .032, mean [SD]; 9.02 [3.62] vs 12.10 [4.13]; P = .001 and mean [SD]; 5.11 [1.79] vs 8.19 [2.99]; P < .005, respectively, IL-1ß. Mean [SD]; 14.83 [5.58] vs 17.55 [3.37]; P = .009, mean [SD]; 11.20 [2.57] vs 14.85 [3.01]; P < .005 and mean [SD]; 8.62 [2.55] vs 11.25 [2.72]; P < .005, respectively, IAP). There were no significant differences in the duration of MV, length of stay in ICU, and 28d mortality between the groups. CONCLUSION: EA at ST36-ST37 attenuated inflammatory responses through reduction in serum levels of TNF-α and IL-1ß and IAP in septic patients with intestinal dysfunction manifested syndrome of obstruction of the bowels Qi.


Assuntos
Eletroacupuntura/métodos , Obstrução Intestinal/terapia , Hipertensão Intra-Abdominal/terapia , Síndrome de Resposta Inflamatória Sistêmica/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Unidades de Terapia Intensiva , Interleucina-1beta/sangue , Obstrução Intestinal/etiologia , Obstrução Intestinal/fisiopatologia , Intestinos/inervação , Intestinos/fisiopatologia , Hipertensão Intra-Abdominal/etiologia , Hipertensão Intra-Abdominal/fisiopatologia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Respiração Artificial/estatística & dados numéricos , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/complicações , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangue , Adulto Jovem
15.
Lancet ; 391(10126): 1186-1196, 2018 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-29551338

RESUMO

BACKGROUND: Patients with systemic lupus erythematosus have T-cell dysfunction that has been attributed to the activation of the mammalian target of rapamycin (mTOR). Rapamycin inhibits antigen-induced T-cell proliferation and has been developed as a medication under the generic designation of sirolimus. We assessed safety, tolerance, and efficacy of sirolimus in a prospective, biomarker-driven, open-label clinical trial. METHODS: We did a single-arm, open-label, phase 1/2 trial of sirolimus in patients with active systemic lupus erythematosus disease unresponsive to, or intolerant of, conventional medications at the State University of New York Upstate Medical University (Syracuse, NY, USA). Eligible participants (aged ≥18 years) had active systemic lupus erythematosus fulfilling four or more of 11 diagnostic criteria defined by the American College of Rheumatology. We excluded patients with allergy or intolerance to sirolimus, patients with life-threatening manifestations of systemic lupus erythematosus, proteinuria, a urine protein to creatinine ratio higher than 0·5, anaemia, leucopenia, or thrombocytopenia. Patients received oral sirolimus at a starting dose of 2 mg per day, with dose adjusted according to tolerance and to maintain a therapeutic range of 6-15 ng/mL. Patients were treated with sirolimus for 12 months. Safety outcomes included tolerance as assessed by the occurrence of common side-effects. The primary efficacy endpoint was decrease in disease activity, assessed using the British Isles Lupus Assessment Group (BILAG) index and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Blood samples of 56 matched healthy individuals were obtained as controls for immunobiological outcomes monitored at each visit. The primary efficacy endpoint was assessed in all patients who completed 12 months of treatment, and all patients who received at least one dose of treatment were included in the safety analyses. This trial is registered with ClinicalTrials.gov, number NCT00779194. FINDINGS: Between March 9, 2009, and Dec 8, 2014, 43 patients were enrolled, three of whom did not meet eligibility criteria. 11 of the 40 eligible patients discontinued study treatment because of intolerance (n=2) or non-compliance (n=9). SLEDAI and BILAG disease activity scores were reduced during 12 months of treatment in 16 (55%) of 29 patients who completed treatment. Mean SLEDAI score decreased from 10·2 (SD 5·6) at enrolment to 4·8 (4·5) after 12 months of treatment (p<0·001) and the mean total BILAG index score decreased from 28·4 (12·4) at enrolment to 17·4 (10·7) after 12 months of treatment (p<0·001). The mean daily dose of prednisone required to control disease activity decreased from 23·7 mg (SD 9·6) to 7·2 mg (2·3; p<0·001) after 12 months of treatment. Sirolimus expanded CD4+CD25+FoxP3+ regulatory T cells and CD8+ memory T-cell populations and inhibited interleukin-4 and interleukin-17 production by CD4+ and CD4-CD8- double-negative T cells after 12 months. CD8+ memory T cells were selectively expanded in SRI-responders. Patient liver function and lymphocyte counts were unchanged. Although HDL-cholesterol (Z=-2·50, p=0·012), neutrophil counts (Z=-1·92, p=0·054), and haemoglobin (Z=-2·83, p=0·005) were moderately reduced during treatment, all changes occurred within a range that was considered safe. Platelet counts were slightly elevated during treatment (Z=2·06, p=0·0400). INTERPRETATION: These data show that a progressive improvement in disease activity is associated with correction of pro-inflammatory T-cell lineage specification in patients with active systemic lupus erythematosus during 12 months of sirolimus treatment. Follow-up placebo-controlled clinical trials in diverse patient populations are warranted to further define the role of mTOR blockade in treatment of systemic lupus erythematosus. FUNDING: Pfizer, the National Institutes of Health, and the Central New York Community Foundation.


Assuntos
Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Sirolimo/uso terapêutico , Adolescente , Adulto , Idoso , Tolerância a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
16.
Surgery ; 163(4): 714-720, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29307573

RESUMO

BACKGROUND: This trial was performed to compare short- and long-term outcomes after laparoscopic left-sided hepatectomy and open left-sided hepatectomy. Left-sided hepatectomy is a novel, minimally invasive operative technique for primary left-sided hepatolithiasis, but it has not been accepted widely due to the limited information about short- and long-term outcomes, effectiveness, and safety compared with the open approach. METHODS: Patients who underwent left-sided hepatectomy between January 2007 and December 2016 were reviewed and grouped into the open left-sided hepatectomy and left-sided hepatectomy groups, according to propensity score matching in terms of age, sex, body mass index, liver function, location of stone, hepatitis serology, and comorbidity on a ratio of 1:1. RESULTS: No significant differences were observed in the demographic characteristics of the 200 patients included in the study. For the left-sided hepatectomy group (100 patients) when compared to the open left-sided hepatectomy group (100 patients, the duration of hospital stay was less (10.3 vs 14.7 days, P< .001), the incidence of postoperative biliary fistulas (5% vs 14%, P = .003) and overall morbidity were less (25% vs 45%, P = .003), out of bed return to activity was expedited (2.0 vs 2.7 days, P< .001), and the rate of stone recurrence in the long-term follow-up was les (5.1% vs 17%, P = .003). CONCLUSION: Left-sided hepatectomy was associated with significantly lesser rate of stone recurrence, a shorter hospital stay, decreased morbidity and clinical biliary fistula rate, and expedited postoperative recovery compared with open left-sided hepatectomy.


Assuntos
Hepatectomia , Laparoscopia , Litíase/cirurgia , Hepatopatias/cirurgia , Adulto , Feminino , Seguimentos , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
17.
Sci Rep ; 7(1): 15375, 2017 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-29133822

RESUMO

Microvascular invasion (MVI) is rarely diagnosed preoperatively in hepatocellular carcinoma (HCC). The aim of this meta-analysis is to assess the diagnostic power of a non-smooth tumor margin on preoperative imaging for MVI. We performed a literature search using the PubMed, Embase and Cochrane Library databases, and 11 studies were included involving 618 MVI-positive cases and 1030 MVI-negative cases. Considerable heterogeneity was found, and was indicated to be attributable to the mean patient ages in the included studies. In subgroups of studies with a mean patient age older than 60 years and studies with computed tomography (CT) as the imaging method (as opposed to magnetic resonance imaging (MRI)), heterogeneity was low, and the diagnostic odds ratio (DOR) of the single two-dimensional imaging feature for MVI was 21.30 (95% CI [12.52, 36.23]) and 28.78 (95% CI [13.92, 59.36]), respectively; this power was equivalent to or greater than that of certain multivariable-based scoring systems. In conclusion, a non-smooth tumor margin on preoperative imaging is of great value for MVI assessment and should be considered for inclusion in future scoring systems.

18.
Eur J Pharm Sci ; 109: 581-586, 2017 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-28917964

RESUMO

Both cocrystal and nanocrystal technologies have been widely used in the pharmaceutical development for poorly soluble drugs. However, the synergistic effects due to the integration of these two technologies have not been well investigated. The aim of this study is to develop a nano-sized cocrystal of phenazopyridine (PAP) with phthalimide (PI) to enhance the release rate and oral bioavailability of PAP. A PAP-PI nano-cocrystal with particle diameter of 21.4±0.1nm was successfully prepared via a sonochemical approach and characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and dynamic light scattering (DLS) analysis. An in vitro release study revealed a significant release rate enhancement for PAP-PI nano-cocrystal as compared to PAP-PI cocrystal and PAP hydrochloride salt. Further, a comparative oral bioavailability study in rats indicated significant improvement in Cmax and oral bioavailability (AUC0-∞) by 1.39- and 2.44-fold, respectively. This study demonstrated that this novel nano-cocrystal technology can be a new promising option to improve release rate and absorption of poorly soluble compounds in the pharmaceutical industry.


Assuntos
Nanopartículas/química , Fenazopiridina/química , Fenazopiridina/farmacocinética , Ftalimidas/química , Ftalimidas/farmacocinética , Administração Oral , Animais , Disponibilidade Biológica , Liberação Controlada de Fármacos , Masculino , Fenazopiridina/sangue , Ratos Sprague-Dawley
19.
Mar Pollut Bull ; 125(1-2): 492-500, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-28807422

RESUMO

To understand the source-to-sink of pollutants in the Kelantan River estuary and the adjacent shelf area in Malaysia, a total of 42 surface sediment samples were collected in the Kelantan River-estuary-shelf system to analyze for grain size, total organic carbon (TOC) content, Al and heavy metals (Cr, Ni, Cu, Zn, Cd and Pb). The surficial sediments were mainly composed of clayey silt and the TOC content in sediments decreased from the river to the shelf. The surficial sediments experienced Pb pollution; Cr only showed a certain level of pollution in the coastal area of the estuary but not in other areas, and Ni, Cu, Zn, and Cd showed no pollution. The heavy metals mainly originated from natural weathering and erosion of rocks and soils in the catchment and enriched near the river mouth. Total organic carbon can promote the enrichment of heavy metals in sediments.


Assuntos
Sedimentos Geológicos/análise , Metais Pesados/análise , Poluentes Químicos da Água/análise , Monitoramento Ambiental , Poluição Ambiental/análise , Estuários , Malásia , Rios
20.
J Appl Biomater Funct Mater ; 15(2): e162-e169, 2017 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-27716871

RESUMO

BACKGROUND: The aim of this study was to develop a minimally invasive hydrogel system that can release strontium ions, an element that has been shown to increase osteoblast proliferation and prohibit bone resorption, in a controlled manner. METHODS: SrCO3 was selected as the salt of choice due to potential acid neutralization reaction between SrCO3 and degradation by-products of methoxy(polyethylene glycol)-co-poly(lactic-co-glycolic acid) (mPEG-PLGA): namely, lactic acid and glycolic acid. SrCO3 was incorporated into mPEG-PLGA hydrogel, and the system was assessed for gelation properties, drug release and biocompatibility. RESULTS: SrCO3 incorporation at hydrogel to SrCO3 ratios of 5:1, 3:1 and 1:1 (wt%) did not compromise the thermosensitivity of mPEG-PLGA hydrogels. Furthermore, incorporation of SrCO3 at 1:1 ratio prevented copolymer self-catalysis and decreased hydrogel weight loss from 85% to 61% in vitro after 30 days. During the 30-day time frame, zero-order strontium release was observed and was correlated to hydrogel degradation and acidity. The addition of SrCO3 also improved in vivo hydrogel biocompatibility, due to moderation of acidic microenvironment and amelioration of inflammatory response. CONCLUSIONS: These results showed that the described system is suitable for the extended release of strontium and exhibits potential for localized treatment for osteoporosis or as a bone void filler.


Assuntos
Preparações de Ação Retardada/química , Hidrogéis/química , Estrôncio/química , Ácido Láctico , Poliésteres , Polietilenoglicóis
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