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1.
Infect Dis Poverty ; 10(1): 8, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33468247

RESUMO

BACKGROUND: The detection of drug-resistant tuberculosis (DR-TB) is a major health concern in China. We aim to summarize interventions related to the screening and detection of DR-TB in Jiangsu Province, analyse their impact, and highlight policy implications for improving the prevention and control of DR-TB. METHODS: We selected six prefectures from south, central and north Jiangsu Province. We reviewed policy documents between 2008 and 2019, and extracted routine TB patient registration data from the TB Information Management System (TBIMS) between 2013 and 2019. We used the High-quality Health System Framework to structure the analysis. We performed statistical analysis and logistic regression to assess the impact of different policy interventions on DR-TB detection. RESULTS: Three prefectures in Jiangsu introduced DR-TB related interventions between 2008 and 2010 in partnership with the Global Fund to Fight AIDS, Tuberculosis and Malaria (the Global Fund) and the Bill & Melinda Gates Foundation (Gates Foundation). By 2017, all prefectures in Jiangsu had implemented provincial level DR-TB policies, such as use of rapid molecular tests (RMT), and expanded drug susceptibility testing (DST) for populations at risk of DR-TB. The percentage of pulmonary TB cases confirmed by bacteriology increased from 30.0% in 2013 to over 50.0% in all prefectures by 2019, indicating that the implementation of new diagnostics has provided more sensitive testing results than the traditional smear microscopy. At the same time, the proportion of bacteriologically confirmed cases tested for drug resistance has increased substantially, indicating that the intervention of expanding the coverage of DST has reached more of the population at risk of DR-TB. Prefectures that implemented interventions with support from the Global Fund and the Gates Foundation had better detection performance of DR-TB patiens compared to those did not receive external support. However, the disparities in DR-TB detection across prefectures significantly narrowed after the implementation of provincial DR-TB polices. CONCLUSIONS: The introduction of new diagnostics, including RMT, have improved the detection of DR-TB. Prefectures that received support from the Global Fund and the Gates Foundation had better detection of DR-TB. Additionally, the implementation of provincial DR-TB polices led to improvements in the detection of DR-TB across all prefectures.

2.
Gut ; 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33257471

RESUMO

OBJECTIVE: Impaired hepatic fatty acids oxidation results in lipid accumulation and redox imbalance, promoting the development of fatty liver diseases and insulin resistance. However, the underlying pathogenic mechanism is poorly understood. Krüppel-like factor 16 (KLF16) is a transcription factor that abounds in liver. We explored whether and by what mechanisms KLF16 affects hepatic lipid catabolism to improve hepatosteatosis and insulin resistance. DESIGN: KLF16 expression was determined in patients with non-alcoholic fatty liver disease (NAFLD) and mice models. The role of KLF16 in the regulation of lipid metabolism was investigated using hepatocyte-specific KLF16-deficient mice fed a high-fat diet (HFD) or using an adenovirus/adeno-associated virus to alter KLF16 expression in mouse primary hepatocytes (MPHs) and in vivo livers. RNA-seq, luciferase reporter gene assay and ChIP analysis served to explore the molecular mechanisms involved. RESULTS: KLF16 expression was decreased in patients with NAFLD, mice models and oleic acid and palmitic acid (OA and PA) cochallenged hepatocytes. Hepatic KLF16 knockout impaired fatty acid oxidation, aggravated mitochondrial stress, ROS burden, advancing hepatic steatosis and insulin resistance. Conversely, KLF16 overexpression reduced lipid deposition and improved insulin resistance via directly binding the promoter of peroxisome proliferator-activated receptor α (PPARα) to accelerate fatty acids oxidation and attenuate mitochondrial stress, oxidative stress in db/db and HFD mice. PPARα deficiency diminished the KLF16-evoked protective effects against lipid deposition in MPHs. Hepatic-specific PPARα overexpression effectively rescued KLF16 deficiency-induced hepatic steatosis, altered redox balance and insulin resistance. CONCLUSIONS: These findings prove that a direct KLF16-PPARα pathway closely links hepatic lipid homeostasis and redox balance, whose dysfunction promotes insulin resistance and hepatic steatosis.

3.
BMC Oral Health ; 20(1): 350, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33261594

RESUMO

BACKGROUND: This is a retrospective study that compares mandibular growth changes in skeletal Class II patients treated by rapid maxillary expansion (RME) and following fixed appliance with those patients treated by Twin-Block (TB) and following fixed appliance. METHODS: Fourteen patients treated by RME and following fixed appliance were included into the RME group. Fifteen patients treated by Twin-Block and following fixed appliance were included into the TB group. Lateral cephalometric radiographs taken before treatment and immediately after fixed appliance treatment were used to evaluate mandibular growth effects. RESULTS: The starting forms of the patients in the two groups were examined to be of good comparability. The mandibular length increased significantly in both groups as measured by Co-Gn, Go-Gn and Ar-Gn, but the TB group didn't show more mandibular growth than the RME group (P > 0.05). Skeletal changes of the mandible in vertical dimension were different in the two groups. The change in FMA was 0.35° in the RME group, while the change was 2.65° in the TB group (P < 0.001). The change in LAFH was 5.14 mm in the RME group, significantly smaller than the change of 10.19 mm in the TB group (P < 0.001). CONCLUSION: The investigated Phase I treatment with RME followed by Phase II treatment of fixed appliance achieved the same increases in sagittal mandibular growth and facial profile improvements as the Twin-Block therapy. The treatment with RME followed by fixed appliance was better for vertical control, while the treatment with Twin-Block followed by fixed appliance significantly increased the mandibular plane angle.

4.
Materials (Basel) ; 13(21)2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33158010

RESUMO

We report first-principles calculations on the structural, mechanical, and electronic properties of O2 molecule adsorption on different graphenes (including pristine graphene (G-O2), N(nitrogen)/B(boron)-doped graphene (G-N/B-O2), and defective graphene (G-D-O2)) under equibiaxial strain. Our calculation results reveal that G-D-O2 possesses the highest binding energy, indicating that it owns the highest stability. Moreover, the stabilities of the four structures are enhanced enormously by the compressive strain larger than 2%. In addition, the band gaps of G-O2 and G-D-O2 exhibit direct and indirect transitions. Our work aims to control the graphene-based structure and electronic properties via strain engineering, which will provide implications for the application of new elastic semiconductor devices.

5.
Arch Med Sci ; 16(4): 931-940, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32542097

RESUMO

Introduction: Lung cancer is the leading cause of cancer-associated mortality worldwide. Recently, long non-coding RNAs (lncRNAs) have been studied as key regulators in some biological processes. Of note, the molecular mechanism and prognostic value of lncRNAs in non-small cell lung cancer (NSCLC) have largely remained unclear. Material and methods: In this study, we compared the PTTG3P expression levels between lung cancer and normal lung samples by analyzing 5 public datasets (GSE18842, GSE19804, GSE27262, GSE30219, and GSE19188). Next, pentose phosphate pathway and co-expression networks were constructed to identify key targets of lncRNA PTTG3P. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to explore the potential roles of lncRNA PTTG3P. Moreover, we constructed PTTG3P-mediated ceRNA networks in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Results: In the present study, our analysis showed that PTTG3P expression was higher in high T stage LUAD and LUSC samples, as well as high N stage NSCLC tissues. Of note, we found that higher PTTG3P expression is correlated with shorter survival time in NSCLC patients by analyzing Kaplan-Meier plotter datasets. We found that PTTG3P was significantly associated with NSCLC cell proliferation regulation by affecting a series of cell cycle related biological processes. Conclusions: Bioinformatics analysis showed that PTTG3P was associated with NSCLC cell proliferation. These results suggested that PTTG3P could serve as a new therapeutic and prognostic target for NSCLC.

6.
Liver Int ; 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32562336

RESUMO

BACKGROUND & AIMS: The lymphocyte-C-reactive protein ratio (LCR) is a novel inflammatory-based score, based solely on the lymphocyte and C-reactive protein. We aimed to clarify the prognostic value of the LCR score in intrahepatic cholangiocarcinoma (ICC) patients after resection. METHODS: We compared the prognostic accuracy of the LCR score with other inflammatory-based scores in this large, multicentre cohort study. The independent variables associated with overall survival (OS) were explored in both the primary (n = 228) and validation cohorts (n = 135). Harrell's concordance index (C-index) was used to compare the predictive ability of all the assessed inflammatory-based scores. RESULTS: The LCR score was differentiated two groups of ICC patients with distinct prognoses (1-, 3-, and 5-year OS rates: 94.4%, 66.3%, and 59.3%; and 66.6%, 45.6%, and 32.7%, respectively) (P < .001). Multivariate analysis showed that the LCR score, as well as the TNM stage and preoperative CA19-9 level, were independently associated with OS. The predictive accuracy of the LCR score (c score: 0.634) was superior to that of the other inflammatory-based scores (c scores: 0.508-0.615). These findings were supported by the external validation cohort. CONCLUSION: The LCR score is stable and consistently the best prognostic score and may offer as a simple, objective and discriminatory method in facilitating the risk stratification of ICC patients.

7.
Biomed Pharmacother ; 128: 110260, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32447213

RESUMO

Melatonin is a pineal-produced indole known for its anti-aging, antiapoptotic and antioxidant properties. In past decades, the protective potentials of melatonin for cardiovascular diseases, such as atherosclerosis and myocardial infarction, have been widely revealed, triggering more investigations focused on other cardioprotective effects of melatonin. Recently, the roles of melatonin in diabetic cardiomyopathy (DCM) have attracted increased attention. In this regard, researchers found that melatonin attenuated cardiac fibrosis and hypertrophy, thus interrupting the development of DCM. Retinoid-related orphan receptor α is a key melatonin receptor that contributed to the cardioprotective effect of melatonin in hearts with DCM. For the downstream mechanisms, the inhibition of mammalian STE20-like kinase 1 plays a pivotal role, which exerts antiapoptotic and proautophagic effects, thus enhancing cardiac tolerance in high-glucose conditions. In addition, other signalling mechanisms, such as sirtuin-1/peroxisome proliferator-activated receptor gamma-coactivator alpha and endoplasmic reticulum-related signalling, are also involved in the protective effects of melatonin on cardiomyocytes under diabetic conditions. This review will focus on the protective signalling mechanisms regulated by melatonin and provide a better understanding of the therapeutic applications of melatonin signalling in DCM.

8.
Oxid Med Cell Longev ; 2020: 7051845, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32256959

RESUMO

Diabetic cardiomyopathy (DCM) is a common cardiovascular complication of diabetic mellitus that is characterized by diastolic disorder in the early stage and clinical heart failure in the later stage. Presently, DCM is considered one of the major causes of death in diabetic patients. Resveratrol (RSV), a naturally occurring stilbene, is widely reported as a cardioprotective substance in many heart diseases. Thus far, the specific roles of RSV in DCM prevention and treatment have attracted great attention. Here, we discuss the roles of RSV in DCM by focusing its downstream targets from both in vivo and in vitro studies. Among such targets, Sirtuins 1/3 and AMP-activated kinase have been identified as key mediators that induce cardioprotection during hyperglycemia. In addition, many other signaling molecules (e.g., forkhead box-O3a and extracellular regulated protein kinases) are also regulated in the presence of RSV and exert beneficial effects such as opposing oxidative stress, inflammation, and apoptosis in cardiomyocytes exposed to high-glucose conditions. The beneficial potential of an RSV/stem cell cotherapy is also reviewed as a promising therapeutic strategy for preventing the development of DCM.

9.
Neural Regen Res ; 15(5): 922-928, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31719258

RESUMO

Stroke is the leading cause of death and long-term disability worldwide, and cognitive impairment and dementia are major complications of ischemic stroke. Cystatin C (CysC) has been found to be a neuroprotective factor in animal studies. However, the relationship between CysC levels and cognitive dysfunction in previous studies has revealed different results. This prospective observational study investigated the correlation between serum CysC levels and post-stroke cognitive dysfunction at 3 months. Data from 638 patients were obtained from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). Cognitive dysfunction was assessed using the Mini-Mental State Examination (MMSE) at 3 months after stroke. According to the MMSE score, 308 patients (52.9%) had post-stroke cognitive dysfunction. After adjusting for potential confounding factors, the odds ratio (95% CI) of post-stroke cognitive dysfunction for the highest quartile of serum CysC levels was 0.54 (0.30-0.98), compared with the lowest quartile. The correlation between serum CysC and cognitive dysfunction was modified by renal function status. We observed a negative linear dose-response correlation between CysC and cognitive dysfunction in patients with normal renal function (Plinearity = 0.044), but not in those with abnormal renal function. Elevated serum CysC levels were correlated with a low risk of 3-month cognitive dysfunction in patients with acute ischemic stroke, especially in those with normal renal function. The current results suggest that CysC is a protective factor for post-stroke cognitive dysfunction, and could be used to treat post-stroke cognitive dysfunction. The CATIS study was approved by the Institutional Review Boards at Soochow University from China (approval No. 2012-02) on December 30, 2012, and was registered at ClinicalTrials.gov (identifier No. NCT01840072) on April 25, 2013.

10.
Ann Transl Med ; 7(20): 563, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31807544

RESUMO

Background: The effects of miR-92a on EPCs are still poorly elucidated. This study aimed to investigate the effects of miR-92a on EPCs (Endothelial progenitor cells) in a model of hypoxia (HO) or high glucose (HG)-induced EPCs injury by targeting GDF11 (Differentiation growth factor 11). Methods: The effects of miR-92a on EPCs subjected to HO or HG were investigated firstly. Subsequently, the action mechanism of miR-92a on EPCs by targeting GDF11 was elucidated. Proliferation, apoptosis, migration, angiogenesis was measured with MTT, flow cytometry, transwell, tube formation respectively. After 24 h, levels of reactive oxygen species (ROS) were measured by fluorescence intensity. LDH and NO (nitric oxide) levels were determined by ELISA. The expression of FLK-1 (fetal liver kinase 1) and vWF (von Willebrand factor) was detected by immunofluorescence. mRNA and protein expression levels were examined using PCR and western blotting respectively. The interaction between miR-92a and GDF11 was evaluated by dual-luciferase reporter assay. Results: Our results showed that HO or HG increased apoptosis, production of LDH and generation of ROS, but decreased the ability of migration and tube formation and generation of NO in EPCs; inhibiting of miR-92a decreased HO or HG-induced injury of EPCs, whereas miR-92a over-expression had the opposite effect; the protective effects induced by inhibiting of miR-92a on EPCs could be reversed by GDF11 siRNA and the harmful effects induced by over-expression of miR-92a could be rescued by over-expression of GDF11, which showed that the harmful effects of miR-92a be related to its inhibition of GDF11 and subsequent inactivation of the SMAD2/3/FAK/Akt/eNOS signaling pathway. Conclusions: Inhibiting miR-92a can protect EPCs from HO or HG-induced injury. The effect of miR-92a on EPCs are mediated by regulating of GDF11 and downstream SMAD2/3/FAK/Akt/eNOS signaling pathway.

11.
BMC Cancer ; 19(1): 1047, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694596

RESUMO

BACKGROUND: The application of laparoscopic liver resection (LLR) has expanded rapidly in recent decades. Although multiple authors have reported LLR shows improved safety and efficacy in treating hepatocellular carcinoma (HCC) compared with open liver resection (OLR), laparoscopic (LMLR) and open (OMLR) major liver resections for HCC treatment remain inadequately evaluated. This work aimed to test the hypothesis that LMLR is safer and more effective than OMLR for HCC. METHODS: Comparative cohort and registry studies on LMLR and OMLR, searched in PubMed, the Science Citation Index, EMBASE, and the Cochrane Library, and published before March 31, 2018, were collected systematically and meta-analyzed. Fixed- and random-effects models were employed for generating pooled estimates. Heterogeneity was assessed by the Q-statistic. RESULTS: Nine studies (1173 patients) were included. Although the pooled data showed operation time was markedly increased for LMLR in comparison with OMLR (weighted mean difference [WMD] 74.1, 95% CI 35.1 to 113.1, P = 0.0002), blood loss was reduced (WMD = - 107.4, 95% CI - 179.0 to - 35.7, P = 0.003), postoperative morbidity was lower (odds ratio [OR] 0.47, 95% CI 0.35 to 0.63, P <  0.0001), and hospital stay was shorter (WMD = - 3.27, 95% CI - 4.72 to - 1.81, P <  0.0001) in the LMLR group. Although 1-year disease-free survival (DFS) was increased in patients administered LMLR (OR = 1.55, 95% CI 1.04 to 2.31, P = 0.03), other 1-, 3-, and 5-year survival outcomes (overall survival [OS] and/or DFS) were comparable in both groups. CONCLUSIONS: Compared with OMLR, LMLR has short-term clinical advantages, including reduced blood loss, lower postsurgical morbidity, and shorter hospital stay in HCC, despite its longer operative time. Long-term oncological outcomes were comparable in both groups.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Laparoscopia/métodos , Neoplasias Hepáticas/cirurgia , Fígado/cirurgia , Estudos de Coortes , Intervalo Livre de Doença , Humanos , Tempo de Internação/estatística & dados numéricos , Fígado/patologia , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos
12.
Am J Orthod Dentofacial Orthop ; 155(3): 398-410, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30826043

RESUMO

This case report describes the induced ankylosis of the primary canines for use as absolute anchorage for maxillary protraction. The patient was a young boy with Class III malocclusion and cleft soft palate. The final occlusion was esthetic, functional, healthy, and stable 4 years after treatment.


Assuntos
Fissura Palatina/cirurgia , Dente Canino , Má Oclusão de Angle Classe III/terapia , Procedimentos de Ancoragem Ortodôntica , Ortodontia Corretiva/métodos , Palato Mole/anormalidades , Anquilose Dental , Cefalometria , Criança , Humanos , Masculino , Má Oclusão de Angle Classe III/diagnóstico por imagem , Palato Mole/cirurgia , Radiografia Panorâmica
13.
J Cell Physiol ; 234(2): 1190-1207, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30132875

RESUMO

Acute myocardial infarction is a major cause of death worldwide. The most important therapy for limiting ischemic injury and infarct size is timely and efficient myocardial reperfusion treatment, which may instead induce cardiomyocyte necrosis due to myocardial ischemia-reperfusion (I/R) injury. Heat shock protein 70 (HSP70), a stress-inducible protein, is overexpressed during myocardial I/R. The induced HSP70 is shown to regulate several intracellular proteins (e.g., transcription factors, enzymes, and apoptosis-related proteins) and signaling pathways (e.g., c-Jun N-terminal kinase pathway and extracellular-signal-regulated kinase 1/2 pathway), forming a complicated network that contributes to reducing reactive oxygen species accumulation, improving calcium homeostasis, inhibiting cellular apoptosis, thereby enhancing the stress adaption of myocardium to I/R injury. In addition, the extracellular HSP70, which is released from injured cardiomyocytes during I/R, acts as a proinflammatory mediator that results in cell death, while the intracellular HSP70 exerts antiinflammatory effects by suppressing proinflammatory signaling pathways. Notably, HSP70 is induced and contributes to the cardioprotection in several types of preconditioning and postconditioning. Meanwhile, it is shown that the cardioprotective effectiveness of preconditioning-induced HSP70 (e.g., hyperthermia preconditioning-induced HSP70) can be impaired by certain pathological conditions, such as hyperlipidemia and hyperglycemia. Thus, we highlight the widespread cardioprotective involvement of HSP70 in preconditioning and postconditioning and elucidate how HSP70-mediated cardioprotection is impaired in these pathological conditions. Furthermore, several therapeutic potentials of HSP70 against myocardial I/R injury and potential directions for future studies are also provided in this review.


Assuntos
Proteínas de Choque Térmico HSP70/metabolismo , Pós-Condicionamento Isquêmico/métodos , Precondicionamento Isquêmico/métodos , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/metabolismo , Animais , Fármacos Cardiovasculares/uso terapêutico , Citoproteção , Proteínas de Choque Térmico HSP70/agonistas , Humanos , Terapia de Alvo Molecular , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Transdução de Sinais , Resultado do Tratamento , Regulação para Cima
14.
Exp Neurol ; 311: 225-233, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30315808

RESUMO

ATP-sensitive potassium (K-ATP) channels, coupling cell metabolism to cell membrane potential, are involved in brain diseases including stroke. Emerging evidence shows that astrocytes play important roles in the pathophysiology of cerebral ischemia. Kir6.1, a pore-forming subunit of K-ATP channel, is prominently expressed in astrocytes and participates in regulating its function. However, the exact role of astrocytic Kir6.1-containg K-ATP channel (Kir6.1/K-ATP) in ischemic stroke remains unclear. Here, we found that astrocytic Kir6.1 knockout (KO) mice exhibited larger infarct areas and more severe brain edema and neurological deficits in middle cerebral artery occlusion stroke model. Both activated gliosis and neuronal loss were aggravated in astrocytic Kir6.1 KO mice. Furthermore, the protein levels of pro-apoptotic protein Bcl-2 associated X (Bax) and active caspase-3 were up-regulated and the expression of anti-apoptotic protein Bcl-2 was down-regulated in astrocytic Kir6.1 KO mice. This is accompanied by enhanced endoplasmic reticulum stress (ER stress) responses in brain tissues and in astrocytes during ischemia/reperfusion (I/R) injury. Finally, inhibition of ER stress rescued astrocyte apoptosis induced by Kir6.1 deletion during I/R injury. Collectively, our findings reveal that astrocytic Kir6.1/K-ATP channel protects brain from cerebral ischemia/reperfusion injury through inhibiting ER stress and suggest that astrocytic Kir6.1/K-ATP channel is a promising therapeutic target for ischemic stroke.


Assuntos
Astrócitos/metabolismo , Isquemia Encefálica/metabolismo , Estresse do Retículo Endoplasmático/fisiologia , Canais KATP/deficiência , Traumatismo por Reperfusão/metabolismo , Animais , Astrócitos/patologia , Isquemia Encefálica/genética , Isquemia Encefálica/patologia , Células Cultivadas , Canais KATP/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/patologia
15.
Org Biomol Chem ; 16(47): 9237-9242, 2018 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-30475365

RESUMO

Cu(i)-Catalyzed diastereoselective carboboration of α-alkyl-substituted α,ß-unsaturated carboxylic esters to produce ß-boryl-α-quaternary carbon esters was developed. The carbon skeletons of dialkyl sulfates, primary allyl halides, and benzyl bromides were transferred to the α-position of the substrates to provide products in moderate to good yields with a diastereoselectivity of >95% in most cases. Substrates bearing a ß-(hetero)aryl substituent gave higher diastereoselectivities than those bearing a linear ß-alkyl substituent. The crystal structure of the potassium trifluoroborate derivative shows that the reactions probably go through a copper(i) enolate intermediate and the diastereoselectivity arises from the electrophilic attack of electrophiles to the less hindered side of the enolates.

16.
BMC Cancer ; 18(1): 643, 2018 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-29879928

RESUMO

BACKGROUND: The optimal therapeutic strategy in UICC stage T3 hepatocellular carcinoma (HCC) patients that maximizes both safety and long-term outcome has not yet been determined. Our aim was to compare clinical outcomes following hepatic resection (HR) versus transarterial chemoembolization (TACE) for stage T3 HCC. METHODS: From 2005 to 2013, 1179 patients with T3 HCC who underwent HR or TACE were divided into two groups, HR group (n = 280) or TACE group (n = 899). The clinical outcomes were compared before and after propensity score matching. RESULTS: The propensity model matched 244 patients in each group for further analyses. After matching, medium overall survival (OS), 1, 3, and 5-year OS rates in TACE group were 11.8 (95%CI, 9.9-13.7) months, 49.6, 16.5, and 8.4%, respectively; which in HR group were 17.8 (95% CI, 14.8-20.8) months, 63.1, 33.3, and 26.4%, respectively; (log rank = 19.908, P < 0.01). Patients in HR group were more likely to develop pleural effusion, compared with those in TACE group (0.4% vs. 5.3%, P = 0.01). However, no significant differences in other adverse events (AEs) were found between two groups. Similar results were also demonstrated prior to the matched analysis. Multivariate analysis indicated that prothrombin time (PT), tumor size, tumor numbers, UICC staging status, and initial treatment were independent prognostic factors. CONCLUSIONS: Our study revealed that TACE was an option for UICC T3 HCC patients. However, HR seemed to be safe and yield a survival benefit compared with TACE, especially for patients with a good underlying liver function.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Hepatectomia/métodos , Neoplasias Hepáticas/terapia , Adulto , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Feminino , Hepatectomia/efeitos adversos , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Análise de Sobrevida , Resultado do Tratamento
17.
Parkinsonism Relat Disord ; 48: 68-73, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29305084

RESUMO

BACKGROUND: Dyskinesia is a troublesome complication of long-term dopaminergic medications in Parkinson's disease (PD) patients. Many factors are reported to be associated with dyskinesia in PD. OBJECTIVE: To investigate the association between sleep quality and dyskinesia in patients with PD. METHODS: Four hundred twenty-five patients with PD were enrolled in this study. Demographic information was collected. Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn and Yahr (H-Y) stage scale were also performed. Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI) were applied to evaluate daytime sleepiness and overall nighttime sleep quality, respectively, in PD patients. RESULTS: Patients with dyskinesia tended to have a longer duration of disease, higher daily levodopa-equivalent dose (LED), H-Y stage, UPDRS II and PSQI score, and a higher percentage of levodopa treatment than those without dyskinesia. After adjusting for age, sex, age at onset of PD, disease duration, UPDRS I, UPDRS II, UPDRS III, cigarette smoking, use of different antiparkinsonian drugs, phenotype, daily LED, and restless leg syndrome (RLS), PSQI score was still associated with dyskinesia, with corresponding ORs 1.111 (95% CI, 1.004-1.229) as a continuous variable, and 2.469 (95% CI, 1.051-5.800) as a categorical variable, respectively. Further analysis of PSQI components showed that subjective sleep quality and sleep latency were associated with dyskinesia in PD patients. CONCLUSIONS: Our data showed that poor nighttime sleep is positively associated with dyskinesia in PD patients. Attention to the management of nighttime sleep quality may be beneficial to dyskinesia in patients with PD.


Assuntos
Discinesia Induzida por Medicamentos/complicações , Distúrbios do Início e da Manutenção do Sono/complicações , Transtornos do Sono-Vigília/complicações , Idoso , Antiparkinsonianos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/tratamento farmacológico , Estudos Retrospectivos , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Inquéritos e Questionários
18.
J Cardiovasc Pharmacol Ther ; 23(1): 46-56, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28466688

RESUMO

Myocardial infarction (MI) is a serious cardiovascular disease resulting in high rates of morbidity and mortality. Although advances have been made in restoring myocardial perfusion in ischemic areas, decreases in cardiomyocyte death and infarct size are still limited, attributing to myocardial ischemia/reperfusion (I/R) injury. It is necessary to develop therapies to restrict myocardial I/R injury and protect cardiomyocytes against further damage after MI. Many studies have suggested that peroxisome proliferator-activated receptor γ (PPARγ), a ligand-inducible nuclear receptor that predominantly regulates glucose and lipid metabolism, is a promising therapeutic target for ameliorating myocardial I/R injury. Thus, this review focuses on the role of PPARγ in cardioprotection during myocardial I/R. The cardioprotective effects of PPARγ, including attenuating oxidative stress, inhibiting inflammatory responses, improving glucose and lipid metabolism, and antagonizing apoptosis, are described. Additionally, the underlying mechanisms of cardioprotective effects of PPARγ, such as regulating the expression of target genes, influencing other transcription factors, and modulating kinase signaling pathways, are further discussed.


Assuntos
Infarto do Miocárdio/fisiopatologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , PPAR gama/metabolismo , Animais , Apoptose/fisiologia , Humanos , Infarto do Miocárdio/terapia , Traumatismo por Reperfusão Miocárdica/terapia , Miócitos Cardíacos/patologia , Estresse Oxidativo/fisiologia , Transdução de Sinais/fisiologia
19.
Biomed Environ Sci ; 30(9): 632-640, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29081337

RESUMO

OBJECTIVE: We aimed to evaluate the combined effect of a family history of cardiovascular disease (CVD) and high serum C-reactive protein (CRP) on the stroke incidence in an Inner Mongolian population in China. METHODS: A prospective cohort study was conducted from June 2002 to July 2012, with 2,544 participants aged 20 years and over from Inner Mongolia, China. We categorized participants into four groups based on the family history of CVD and CRP levels. RESULTS: We adjusted for age; sex; smoking; drinking; hypertension; body mass index; waist circumference; and blood glucose, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels. Compared with the group with no family history of CVD/low CRP levels, the group with family history of CVD/high CRP levels had a hazard ratio (HR) of 1.78 [95% confidence interval (CI), 1.03-3.07; P = 0.039] of stroke, and an HR of 2.14 (95% CI, 1.09-4.20; P = 0.027) of ischemic stroke. The HRs of hemorrhagic stroke for the other three groups were not statistically significant (all P > 0.05). CONCLUSION: Participants with both a family history of CVD and high CRP levels had the highest stroke incidence, suggesting that high CRP levels may increase stroke risk, especially of ischemic stroke, among individuals with a family history of CVD.


Assuntos
Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/genética , Acidente Vascular Cerebral/epidemiologia , Grupo com Ancestrais do Continente Asiático , China , Predisposição Genética para Doença , Humanos , Estudos Prospectivos , Fatores de Risco
20.
Neurosci Bull ; 33(5): 483-492, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28924920

RESUMO

The enteric nervous system (ENS) controls the function of the gastrointestinal tract and has been implicated in various diseases, including Parkinson's disease (PD). PD is a neurodegenerative disease with Lewy bodies (LBs) and Lewy neurites (LNs) as the main pathological features. In addition to the typical motor symptoms in PD, attention has been drawn to non-motor symptoms, such as constipation, implying dysfunction of the ENS. In the present study, we characterized the age-dependent morphological alterations and aggregation of α-synuclein (α-syn), the primary protein component in LBs and LNs, in the ENS in an α-syn transgenic mouse model. We found that the expression and accumulation of α-syn increased gradually in neurons of Meissner's and Auerbach's plexuses of the gastrointestinal tract with age (from 1 week to 2 years). In addition, α-syn was increasingly phosphorylated at the serine 129 residue, reflecting pathological alterations of the protein over time. Furthermore, α-syn was present in different subtypes of neurons expressing vasoactive intestinal polypeptide, neuronal nitric oxide synthase, or calretinin. The results indicated that BAC-α-Syn-GFP transgenic mice provide a unique model in which to study the relationship between ENS and PD pathogenesis.


Assuntos
Modelos Animais de Doenças , Sistema Nervoso Entérico/metabolismo , Doença de Parkinson/metabolismo , alfa-Sinucleína/metabolismo , Fatores Etários , Animais , Camundongos , Camundongos Transgênicos , Neurônios/metabolismo , Fosforilação , alfa-Sinucleína/genética
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