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1.
Bioorg Chem ; 150: 107571, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38936048

RESUMO

In recent years, Varicocele (VC) has been recognized as a common cause of male infertility that can be treated by surgery or drugs. How to reduce the damage of VC to testicular spermatogenic function has attracted extensive attention in recent years. Among them, overexpressed ROS and high levels of inflammation may play a key role in VC-induced testicular damage. As the key mediated innate immune pathways, cGAS-STING shaft under pathological conditions, such as in cell and tissue damage stress can be cytoplasmic DNA activation, induce the activation of NLRP3 inflammatory corpuscle, triggering downstream of the inflammatory cascade reaction. Chlorogenic acid (CGA), as a natural compound from a wide range of sources, has strong anti-inflammatory and antioxidant activities, and is a potential effective drug for the treatment of varicocele infertility. The aim of this study is to investigate the role of CGA in the spermatogenic dysfunction of the rat testis induced by VC and the potential mechanisms. The results of this study have shown that CGA gavage treatment ameliorated the pathological damage of seminiferous tubules, increased the number of sperm in the lumen, and increased the expression levels of Occludin and ZO-1, which indicated the therapeutic effect of CGA on spermatogenic dysfunction in the testis of VC rats. Meanwhile, the damage of mitochondrial structure was alleviated and the expression levels of ROS, NLRP3 and pro-inflammatory cytokines (IL-1ß, IL-6, IL-18) were significantly reduced in the testicular tissues of model rats after CGA treatment. In addition, we demonstrated for the first time the high expression status of cGAS and STING in testicular tissues of VC model rats, and this was ameliorated to varying degrees after CGA treatment. In conclusion, this study suggests that CGA can improve the spermatogenic function of the testis by reducing mitochondrial damage and inhibiting the activation of the cGAS-STING axis, inhibiting the activation of the NLRP3 inflammasome, and improving the inflammatory damage of the testis, highlighting the potential of CGA as a therapeutic agent for varicocele infertility.

2.
Cell Biol Toxicol ; 39(6): 2527-2549, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37889357

RESUMO

Cardiovascular disease (CVD) caused by anti-cancer drug-induced cardiotoxicity is now the second leading cause of mortality among cancer survivors. It is necessary to establish efficient in vitro models for early predicting the potential cardiotoxicity of anti-cancer drugs, as well as for screening drugs that would alleviate cardiotoxicity during and post treatment. Human induced pluripotent stem cells (hiPSCs) have opened up new avenues in cardio-oncology. With the breakthrough of tissue engineering technology, a variety of hiPSC-derived cardiac microtissues or organoids have been recently reported, which have shown enormous potential in studying cardiotoxicity. Moreover, using hiPSC-derived heart-on-chip for studying cardiotoxicity has provided novel insights into the underlying mechanisms. Herein, we summarize different types of anti-cancer drug-induced cardiotoxicities and present an extensive overview on the applications of hiPSC-derived cardiac microtissues, cardiac organoids, and heart-on-chips in cardiotoxicity. Finally, we highlight clinical and translational challenges around hiPSC-derived cardiac microtissues/organoids/heart-on chips and their applications in anti-cancer drug-induced cardiotoxicity. • Anti-cancer drug-induced cardiotoxicities represent pressing challenges for cancer treatments, and cardiovascular disease is the second leading cause of mortality among cancer survivors. • Newly reported in vitro models such as hiPSC-derived cardiac microtissues/organoids/chips show enormous potential for studying cardio-oncology. • Emerging evidence supports that hiPSC-derived cardiac organoids and heart-on-chip are promising in vitro platforms for predicting and minimizing anti-cancer drug-induced cardiotoxicity.


Assuntos
Antineoplásicos , Doenças Cardiovasculares , Células-Tronco Pluripotentes Induzidas , Neoplasias , Humanos , Cardiotoxicidade/etiologia , Miócitos Cardíacos , Avaliação Pré-Clínica de Medicamentos , Antineoplásicos/efeitos adversos , Neoplasias/tratamento farmacológico , Organoides
3.
Cell Mol Life Sci ; 79(7): 394, 2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-35786773

RESUMO

Iron is an essential micro-element, involved in multiple biological activities in vertebrates. Excess iron accumulation has been identified as an important mediator of lipid deposition. However, the underlying mechanisms remain unknown. In the present study, we found that a high-iron diet significantly increased intestinal iron content and upregulated the mRNA expression of two iron transporters (zip14 and fpn1). Intestinal iron overload increased lipogenesis, reduced lipolysis and promoted oxidative stress and mitochondrial dysfunction. Iron-induced lipid accumulation was mediated by hypoxia-inducible factor-1 α (HIF1α), which was induced in response to mitochondrial oxidative stress following inhibition of prolyl hydroxylase 2 (PHD2). Mechanistically, iron promoted lipid deposition by enhancing the DNA binding capacity of HIF1α to the pparγ and fas promoters. Our results provide experimental evidence that oxidative stress, mitochondrial dysfunction and the HIF1α-PPARγ pathway are critical mediators of iron-induced lipid deposition.


Assuntos
Ferro , PPAR gama , Animais , Lipídeos , Mitocôndrias , Estresse Oxidativo , PPAR gama/genética
4.
BMC Oral Health ; 23(1): 28, 2023 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-36650491

RESUMO

BACKGROUND: It is difficult for orthodontists to accurately predict the growth trend of the mandible in children with anterior crossbite. This study aims to develop a deep learning model to automatically predict the mandibular growth result into normal or overdeveloped using cephalometric radiographs. METHODS: A deep convolutional neural network (CNN) model was constructed based on the algorithm ResNet50 and trained on the basis of 256 cephalometric radiographs. The prediction behavior of the model was tested on 40 cephalograms and visualized by equipped with Grad-CAM. The prediction performance of the CNN model was compared with that of three junior orthodontists. RESULTS: The deep-learning model showed a good prediction accuracy about 85%, much higher when compared with the 54.2% of the junior orthodontists. The sensitivity and specificity of the model was 0.95 and 0.75 respectively, higher than that of the junior orthodontists (0.62 and 0.47 respectively). The area under the curve value of the deep-learning model was 0.9775. Visual inspection showed that the model mainly focused on the characteristics of special regions including chin, lower edge of the mandible, incisor teeth, airway and condyle to conduct the prediction. CONCLUSIONS: The deep-learning CNN model could predict the growth trend of the mandible in anterior crossbite children with relatively high accuracy using cephalometric images. The deep learning model made the prediction decision mainly by identifying the characteristics of the regions of chin, lower edge of the mandible, incisor teeth area, airway and condyle in cephalometric images.


Assuntos
Aprendizado Profundo , Má Oclusão , Humanos , Criança , Mandíbula/diagnóstico por imagem , Redes Neurais de Computação , Radiografia , Má Oclusão/diagnóstico por imagem
5.
Gut ; 70(11): 2183-2195, 2021 11.
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.


Assuntos
Fatores de Transcrição Kruppel-Like/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , PPAR alfa/metabolismo , Animais , Biomarcadores/sangue , Hepatócitos/metabolismo , Humanos , Resistência à Insulina , Lipídeos/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL
6.
Liver Int ; 41(2): 378-387, 2021 02.
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.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neoplasias dos Ductos Biliares/cirurgia , Proteína C-Reativa , Colangiocarcinoma/cirurgia , Estudos de Coortes , Hepatectomia , Humanos , Linfócitos , Prognóstico
7.
Hepatol Res ; 51(11): 1164-1169, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33991153

RESUMO

AIMS: Molecular profiling of hepatocellular carcinoma (HCC) has helped identify actionable genomic alterations that could guide therapeutic decision-making and clinical trial enrollment. However, in clinical practice, next-generation sequencing (NGS) is not extensively used in routine clinical care to identify patients with HCC who are likely to benefit from genome-directed targeted therapies. METHODS: Here, we describe the case of a 66-year-old man with advanced HCC. After rapid progression on transarterial chemoembolization, the tissue sample obtained from biopsy was subjected to NGS to verify whether precision therapy was an option. RESULTS: Our analysis revealed high MET amplification. The patient received crizotinib (250 mg, bid) and showed a remarkable response. CONCLUSIONS: Our case report suggests NGS could help identify patients with high MET amplification in HCC who were likely to benefit from MET inhibitors; moreover, this requires further investigation in clinical trials.

8.
Int J Mol Sci ; 22(9)2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33925909

RESUMO

The steroid hormones are required for gonadal development in fish. The present study was undertaken to characterize the cDNA and promoter sequences of TSPO and SMAD4 genes in yellow catfish Pelteobagrus fulvidraco, explored the mRNA tissue expression and deciphered their promoter regions. Yellow catfish TSPO and SMAD4 shared the similar domains to the corresponding genes from other vertebrates. The TSPO and SMAD4 mRNAs were widely expressed in the detected tissues, but at different levels. Several transcription factors were predicted, such as Sp, GATA, AP1, SOX1, SRY, STAT, HNF4α, PPARγ, Pu.1 and FOXL2. PPARγ overexpression increased but STAT3 overexpression reduced TSPO promoter activity, and FOXL2 overexpression inhibited the promoter activity of TSPO and SMAD4. The site mutation and EMSA analysis indicated that TSPO promoter possessed STAT3 and FOXL2 sites. Overall, our provided the novel understanding into the transcriptionally regulatory mechanisms of TSPO and SMAD4 in fish.


Assuntos
Peixes-Gato/genética , Regulação da Expressão Gênica , Receptores de GABA , Proteína Smad4 , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Regiões Promotoras Genéticas , Receptores de GABA/genética , Receptores de GABA/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Proteína Smad4/genética , Proteína Smad4/metabolismo
9.
BMC Oral Health ; 20(1): 350, 2020 12 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.


Assuntos
Má Oclusão Classe II de Angle , Técnica de Expansão Palatina , Cefalometria , Humanos , Má Oclusão Classe II de Angle/diagnóstico por imagem , Má Oclusão Classe II de Angle/terapia , Mandíbula/diagnóstico por imagem , Desenho de Aparelho Ortodôntico , Estudos Retrospectivos , Resultado do Tratamento
10.
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
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 Classe III de Angle/terapia , Procedimentos de Ancoragem Ortodôntica , Ortodontia Corretiva/métodos , Palato Mole/anormalidades , Anquilose Dental , Cefalometria , Criança , Humanos , Masculino , Má Oclusão Classe III de Angle/diagnóstico por imagem , Palato Mole/cirurgia , Radiografia Panorâmica
13.
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
14.
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.

15.
Org Biomol Chem ; 15(30): 6323-6327, 2017 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-28730195

RESUMO

The Cu(i)-catalyzed stereoconvergent borylative cyclization of ω-mesylate-α,ß-unsaturated compounds is facilitated by a simple Cu-bisphosphine catalyst. This reaction provides a novel route to cis-ß-boron-substituted five- and six-membered carbocycle and heterocycle esters. Mechanistic studies indicate that stereoconvergence and cis-substitution likely stem from the rapid enolation of the borylcopper adduct with the substrate double bond and the formation of a five-membered intermediate, respectively.

16.
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 , Povo Asiático , China , Predisposição Genética para Doença , Humanos , Estudos Prospectivos , Fatores de Risco
17.
Biomed Environ Sci ; 29(1): 12-23, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26822509

RESUMO

OBJECTIVE: Waist circumference, waist-to-hip ratio and waist-to-height ratio, which are the indicators or measures of abdominal adiposity, have long been hypothesized to increase the risk of stroke; yet evidence accumulated till date is not conclusive. Here, we conducted a dose-response meta-analysis to summarize evidences of the association between these measures of abdominal adiposity and the risk of stroke. METHODS: PubMed and Web of Science databases were searched from inception to May 2015. Two investigators independently conducted the study selection and data extraction. Dose-response relationships were assessed by the generalized least squares trend estimation, while the summary effect estimates were evaluated by the use of fixed- or random-effect models. Subgroup and sensitivity analyses were performed to assess the potential sources of heterogeneity and the robustness of the pooled estimation. Publication bias of the literature was evaluated using Begg's and Egger's test. RESULTS: Altogether 15 prospective cohort studies were identified in this study. The summary of relative risks (95% confidence intervals) of stroke for the highest versus the lowest categories was 1.28 (1.18-1.40) for waist circumference, 1.32 (1.21-1.44) for waist-to-hip ratio, and 1.49 (1.24-1.78) for waist-to-height ratio. For a 10-cm increase in waist circumference, the relative risk of stroke increased by 10%; for a 0.1-unit increase in waist-to-hip ratio, the relative risk increased by 16%; and for a 0.05-unit increase in waist-to-height ratio, the relative risk increased by 13%. There was evidence of a nonlinear association between waist-to-hip ratio and stroke risk, Pnonlinearity=0.028. CONCLUSION: Findings from our meta-analysis indicated that waist circumference, waist-to-hip ratio, and waist-to-height ratio were positively associated with the risk of stroke, particularly ischemic stroke.


Assuntos
Gordura Abdominal , Acidente Vascular Cerebral/etiologia , Humanos , Fatores de Risco , Circunferência da Cintura , Relação Cintura-Quadril
18.
Biomed Environ Sci ; 29(7): 467-74, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27554116

RESUMO

OBJECTIVE: We aimed to investigate the cumulative effect of high CRP level and apolipoprotein B-to-apolipoprotein A-1 (ApoB/ApoA-1) ratio on the incidence of ischemic stroke (IS) or coronary heart disease (CHD) in a Mongolian population in China. METHODS: From June 2003 to July 2012, 2589 Mongolian participants were followed up for IS and CHD events based on baseline investigation. All the participants were divided into four subgroups according to C-reactive protein (CRP) level and ApoB/ApoA-1 ratio. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the IS and CHD events in all the subgroups. RESULTS: The HRs (95% CI) for IS and CHD were 1.33 (0.84-2.12), 1.14 (0.69-1.88), and 1.91 (1.17-3.11) in the 'low CRP level with high ApoB/ApoA-1', 'high CRP level with low ApoB/ApoA-1', and 'high CRP level with high ApoB/ApoA-1' subgroups, respectively, in comparison with the 'low CRP level with low ApoB/ApoA-1' subgroup. The risks of IS and CHD events was highest in the 'high CRP level with high ApoB/ApoA-1' subgroup, with statistical significance. CONCLUSION: High CRP level with high ApoB/ApoA-1 ratio was associated with the highest risks of IS and CHD in the Mongolian population. This study suggests that the combination of high CRP and ApoB/ApoA-1 ratio may improve the assessment of future risk of developing IS and CHD in the general population.


Assuntos
Apolipoproteínas A/metabolismo , Apolipoproteínas B/metabolismo , Proteína C-Reativa/metabolismo , Doença das Coronárias/etiologia , Acidente Vascular Cerebral/etiologia , Adulto , Apolipoproteínas A/classificação , Apolipoproteínas A/genética , Apolipoproteínas B/genética , Proteína C-Reativa/genética , Estudos de Coortes , Doença das Coronárias/epidemiologia , Regulação da Expressão Gênica , Humanos , Mongólia/epidemiologia , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Adulto Jovem
19.
Thorac Cardiovasc Surg ; 63(4): 328-34, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24715527

RESUMO

BACKGROUNDS: What is the optimal way for the middle esophageal cancer? It is still controversial. In this study, the clinical outcome of middle thoracic esophageal cancer with either intrathoracic or cervical anastomosis was analyzed in our department. PATIENTS AND METHODS: A total of 205 patients who suffered from middle thoracic esophageal cancer were divided into two groups. In group A, 91 patients received intrathoracic anastomosis above aortic arch after esophageal resection via single left thoracotomy, and in group B, 114 patients received cervical anastomosis after esophageal resection via right thoracotomy and median laparotomy. Data of these patients were collected, and morbidity and mortality were analyzed retrospectively. Survival rate was estimated using the Kaplan-Meier method and comparisons between groups were performed with log-rank test. Univariate and multivariate analyses were performed using Cox model to look for independent predictors of survival. RESULTS: Postoperative complications occurred more frequently in group B, such as hemorrhage (p = 0.011), wound infection (p = 0.032), and temporary paresis of the recurrent laryngeal nerve (p = 0.001). Morbidity of anastomotic leak was higher in group B (8.8 vs. 2.2%; p = 0.048), but the associated mortality was not increased. The extent of radical esophagectomy and lymphadenectomy was much greater in group B; therefore, longer esophagus was resected that reduced the cancer residual rate, and more positive lymph nodes were detected that enhanced the accuracy of clinical staging. Fortunately, more patients received adjuvant therapy after operation in group B, and the 5-year survival rate was improved. CONCLUSION: Anastomotic leak rate was higher in cervical anastomosis but with lower mortality. The 5-year survival rate was improved in cervical anastomosis group. The present data support the assumption that cervical anastomosis is a safer and more beneficial procedure for patients with middle thoracic esophageal cancer.


Assuntos
Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Idoso , Anastomose Cirúrgica , Fístula Anastomótica/etiologia , China , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Esofagectomia/efeitos adversos , Esofagectomia/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
20.
World J Surg Oncol ; 13: 310, 2015 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-26542373

RESUMO

BACKGROUND: In China, the middle esophageal squamous cell cancer is the most common tumor type, and Mckeown esophagectomy (ME) is preferably adopted by thoracic surgeon. But, the surgical trauma of ME is great. Thoracolaparoscopic esophagectomy (TE) was developed to decrease the operative stress; however, the safety and efficacy were not defined. In this study, clinical outcomes were compared between patients who received ME and TE. METHODS: The data of 113 patients who suffered from middle-thoracic esophageal cancer during the same period were collected. Sixty-two patients received ME (ME group), and 51 patients received TE (TE group). Patients' demographics and short-term clinicopathologic outcomes were comparable between the two groups. Survival rate was estimated using the Kaplan-Meier method, and comparisons between groups were performed with log-rank test. RESULTS: Patients in TE group had lower body mass index (BMI). Preoperative tumor stage in TE group was much earlier. Both overall and thoracic operation time were longer in TE group. The blood loss during operation and postoperative day (POD) 1 was less in TE group, which contributed to the less blood transfusion. In TE group, postoperative incidence of pulmonary complications and atrial fibrillation (p = 0.035 and p = 0.033) was lower; the inflammatory response and incision pain were significantly alleviated; the ICU and in-hospital stay was shorter as well because of less surgical trauma. No statistically significant difference was found between two groups in terms of overall survival or disease-free survival. CONCLUSIONS: The efficacy and safety of TE were supported by the selected patients in this cohort study. Although it is lack of randomness in this research, some advantages of TE were gratifying such as lower postoperative complications and similar survival with ME. A multicenter prospective randomized study is now required.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Laparoscopia , Toracoscopia , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , China , Estudos de Coortes , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de Sobrevida , Resultado do Tratamento
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