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1.
Medicine (Baltimore) ; 98(40): e17411, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577753

RESUMO

Evidence on the prescription patterns of antihypertensive drug use in children and adolescents in China is scarce. A descriptive analysis of the Beijing Medical Claim Data, which covered over 95% of the urban residents, was conducted to investigate antihypertensive prescribing patterns and trends in children and adolescents aged under 18 from 2009 to 2014 in Beijing, China. An additional meta-analysis of trends in hypertension prevalence was conducted to compare trends with antihypertensive medications.A total of 11,882 patients received at least 1 prescription for antihypertensive drugs from 2009 to 2014. The number of annual antihypertensive users increased from 2009 to 2012, then declined steadily until 2014, which was consistent with the trend of the hypertension prevalence estimated from the meta-analysis. ß-receptor blockers, thiazide diuretics, and angiotensin-converting enzyme inhibitors were the 3 most commonly prescribed antihypertensive drugs. More boys took the antihypertensive drugs than girls. For users aged under 3 years, thiazide diuretics, α-receptor blockers, and angiotensin-converting enzyme inhibitors were the most prescribed drugs, while ß-receptor blockers, thiazide diuretics were the most used drugs for users above 3 years.In conclusion, antihypertensive drug prescribing for children and adolescents increased from 2009 to 2014, with different characteristics in different subgroups.

2.
J Asian Nat Prod Res ; : 1-7, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31580152

RESUMO

Seven compounds were isolated from a marine-derived fungus Aspergillus sp. ZF-79, including three new polyketides (1-3), named asperochrins D-F, along with four known compounds 4-7. Their structures were determined on the basis of spectroscopic methods. All the compounds were tested for quorum sensing inhibitory (QSI) activity. Compounds 1, 3, 4, 5, and 6 exhibited QSI activity against Chromobacterium violaceum CV026 with MIC values of 50, 100, 50, 50, and 6.25 µM, respectively.

3.
Nat Genet ; 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31578528

RESUMO

Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A transactivated the promoter of ABCG2, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.

4.
Cardiovasc Diabetol ; 18(1): 125, 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31558158

RESUMO

BACKGROUND: Insulin resistance (IR) is considered as a risk factor for atrial fibrillation (AF) even before diabetes develops. The pathophysiology and underlying mechanism are largely unclear. METHODS: We investigated the corresponding mechanism in two IR models of rats fed 15-week high-fat (HFa) and high-fructose/cholesterol (HFr) diets. AF was evaluated and induced by burst atrial pacing. Isolated atrial myocytes were used for whole-cell patch clamp and calcium assessment. Ex vivo whole heart was used for optical mapping. Western blot and immunofluorescence were used for quantitative protein evaluation. RESULTS: Both HFa and HFr rat atria were vulnerable to AF evaluated by burst atrial pacing. Isolated atrial myocytes from HFa and HFr rats revealed significantly increased sarcoplasmic reticulum calcium content and diastolic calcium sparks. Whole-heart mapping showed prolonged calcium transient duration, conduction velocity reduction, and repetitive ectopic focal discharge in HFa and HFr atria. Protein analysis revealed increased TGF-ß1 and collagen expression; increased superoxide production; abnormal upregulation of calcium-homeostasis-related proteins, including oxidized CaMKIIδ, phosphorylated-phospholamban, phosphorylated-RyR-2, and sodium-calcium exchanger; and increased Rac1 activity in both HFa and HFr atria. We observed that inhibition of CaMKII suppressed AF in both HF and HFr diet-fed rats. In vitro palmitate-induced IR neonatal cardiomyocytes and atrial fibroblasts expressed significantly more TGF-ß1 than did controls, suggesting paracrine and autocrine effects on both myocytes and fibroblasts. CONCLUSIONS: IR engenders both atrial structural remodeling and abnormal intracellular calcium homeostasis, contributing to increased AF susceptibility. The inhibition of CaMKII may be a potential therapeutic target for AF in insulin resistance.

5.
Biomed Pharmacother ; 120: 109462, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31542615

RESUMO

Diosbulbin-B (DB) was the main compound of Dioscorea bulbifera L, which was widely used for cancer treatment in Asia. However, the hepatotoxicity induced by high-dose DB seriously limited its possibility using for gastric cancer (GC) treatment in clinic. In this study, we found that DB inhibited GC cells and hepatocytes cell viability in a dose- and time-dependent manner. Specifically, high-dose DB (50µM) significantly inhibited cell proliferation and promoted cell apoptosis, while low dose DB (12.5µM) had little effects on cell viability. Besides, high-dose DB (50µM) significantly decreased CircRNA CDR1as levels in gastric cancer cells instead of hepatocytes. Notably, knock-down of CircRNA CDR1as triggered low-dose DB (12.5µM) induced GC cell death, but had little effects on hepatocytes proliferation and apoptosis. Further results showed that CircRNA CDR1as increased REGγ expressions in GC cells by sponging miR-7-5p, and high-dose DB (50µM) increased miR-7-5p levels and inhibited REGγ expressions in GC cells instead of hepatocytes. In addition, either downregulated miR-7-5p or overexpressed REGγ reversed the promoting effects of downregulated CircRNA CDR1as on low-dose DB-induced GC cell death. Taken together, we concluded that knock-down of CircRNA CDR1as specifically promoted the cytotoxic effects of low-dose DB on GC cells instead of hepatocytes by regulating miR-7-5p/REGγ axis.

6.
J Agric Food Chem ; 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31560530

RESUMO

The design of gelatin-based hydrogels with high mechanical strength, high gelation temperature, and a rapid self-healing property still presents a challenge to researchers. In the present study, single cross-linked gelatin-oxidized tannic acid (SC-GT/OTA) hydrogels were fabricated through covalent cross-linking between gelatin and tannic acid (TA) oxidized by using sodium periodate (NaIO4). Double cross-linked gelatin-OTA-FeCl3·6H2O (DC-GT/OTA/FeIII) hydrogels were also created using metal coordination bonds formed between the catechol groups present in OTA and FeIII in ferric chloride. As a result, the maximum gelling temperature of the SC-GT/OTA hydrogel (37 °C) was considerably higher than that of the pure gelatin hydrogel (15.4 °C). Moreover, the maximum values of compressive stress of SC-GT/OTA hydrogels increased significantly by almost seven times the original value as the molar ratio of NaIO4 to TA increased from 3:1 to 5:1. When the molar ratio of NaIO4 to TA was maintained at the constant of 4:1, the storage modulus values of DC-GT/OTA/FeIII hydrogels with the FeIII-to-TA molar ratio of 1.5:1 were three to 4 orders of magnitude higher than those of SC-GT/OTA hydrogels in the whole angular frequency range. The double cross-linked gelatin hydrogels developed in this research can be used widely in agriculture and material science fields.

7.
Acta Biomater ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31499197

RESUMO

Pancreatic ductal adenocarcinoma (PDA) is a highly fatal disease with 5-year survival of ∼8.5%. Nanoplatforms such as nab-paclitaxel and nanoliposomal irinotecan demonstrate superiority and utility in treating different progressions of PDA by prolonging the median overall survival by only a few months. Due to the dense surrounding stroma and the high autophagy in pancreatic cancer, integrin ɑvß3 targeting, acid environmental sensitive, TR peptide-modified liposomal platforms loaded with combined autophagy inhibiting hydroxychloroquine (HCQ), and cytotoxic paclitaxel (PTX) were designed (TR-PTX/HCQ-Lip) to accomplish the aim of synergistically killing tumor cells while inhibiting stroma fibrosis. The results showed that TR peptide-modified liposomes (TR-Lip) have superior targeting and penetrating effects both in vitro and in vivo. TR-PTX/HCQ-Lip efficiently inhibited autophagy in pancreatic cells and surrounding cancer-associated fibroblasts. The synergistic anti-fibrosis roles were also confirmed both in vitro and in vivo, all of which contributes to the enhanced curative effects of TR-PTX/HCQ-Lip in both heterogenetic and orthotopic pancreatic cancer models. STATEMENT OF SIGNIFICANCE: Autophagy plays a significant role in pancreatic ductal adenocarcinoma, especially in activating cancer associated fibroblasts which is also related to collagen generation that promotes the formation of dense stroma, which hinder the cytotoxic drugs to target and kill cancer cells. In this study, we designed integrin ɑvß3 targeting, acid environmental sensitive liposomal platforms to co-loaded paclitaxel and the autophagy inhibitor hydroxychloroquine. The results showed that the muti-functional liposomes can target to the pancreatic tumor and efficiently kill tumor cells and inhibit stroma fibrosis, thus improve the therapeutic effect in orthotopic pancreatic cancer models.

8.
Chemosphere ; 237: 124467, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31549677

RESUMO

In the present study, the carcinogenic effects of the wastewater sample collected from the Dongming Canal in Shijiazhuang city were first detected by the rat medium-term liver bioassay. The experiment contained five groups: a negative control group, a DEN-alone group, 25% wastewater, 50% wastewater, and 100% wastewater. The body weight of rats decreased significantly as the dose increased. Morphologically, we also found that the damage of the hepatic lobule was more serious and the proliferation of liver cells was more obvious as the dose increased. In addition, we observed a significantly increased liver organ coefficient in rat. With the increase in dose, the damage of the hepatocytes was more serious, which was manifested in significantly elevated of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gammaglutamyl transfer peptide enzyme (γ-GT). And, the irrigative wastewater significantly increased GST-p in the liver of rats at both the transcriptional and translational levels dose-dependently, eventually causing precancerous lesions in the liver tissues. CYP1A1 and CYP1B1 expressions in the rat liver cells at the level of transcription and translation were also significantly increased dose-dependently. Our data clearly demonstrated that the irrigative wastewater had a carcinogenetic effect that was associated with CYP1A1 and CYP1B1. The risk of carcinogenic potential to human health might be due to joint action and accumulative effects over a long period of exposure. We can also concluded that the medium-term liver bioassay could be used as an effective method for evaluating the carcinogenicity of complex water mixtures such as irrigative wastewater.

9.
Oncogene ; 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477834

RESUMO

The functional effects of long noncoding RNAs (lncRNAs) in cancer have been widely recognized. However, there is little research on SCLC-related lncRNAs. Here, long intergenic nonprotein coding RNA 173 (Linc00173) was first shown to be involved in chemoresistance and progression of small-cell lung cancer (SCLC). We found that Linc00173 was highly expressed in SCLC chemoresistant cell lines, and promoted SCLC cells chemoresistance, proliferation, and migration-invasion. Animal studies validated that Linc00173 induced tumor chemoresistance and growth of SCLC in vivo. Moreover, Linc00173 upregulated Etk through functioning as a competitive endogenous RNA (ceRNA) by "sponging" miRNA-218 and led to the upregulation of GSKIP and NDRG1, resulting in the translocation of ß-catenin. Importantly, expression analysis revealed that both Linc00173 and Etk were upregulated in SCLC patient samples and exhibiting positive Linc00173/Etk correlation. High expression of Linc00173 closely correlated with chemoresistance, extensive stage, and shorter survival in SCLC patients. Collectively, our study illustrated a Linc00173-mediated process that facilitated chemoresistance and progression in SCLC, which might provide treatment strategy against SCLC.

10.
Opt Express ; 27(14): 19331-19347, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31503694

RESUMO

Sensing of leakage at an early stage is crucial for the safe utilization of hydrogen. Optical hydrogen sensors eliminate the potential hazard of ignition caused by electrical sparks but achieve a detection limit far higher than their electrical counterparts so far. To essentially improve the performance of optical hydrogen sensors in terms of detection limit, we demonstrate in this work a plasmonic hydrogen sensor based on aluminum-palladium (Al-Pd) hybrid nanorods. Arranged into high-density regular arrays, the hybrid nanorods are capable of sensing hydrogen at a concentration down to 40 ppm, i.e., one thousandth of the lower flammability limit of hydrogen in air. Different sensing behaviors are found for two sensor configurations, where Pd-Al nanorods provide larger spectral shift and Al-Pd ones exhibit shorter response time. In addition, the plasmonic hydrogen sensors here utilize exclusively CMOS-compatible materials, holding the potential for real-world, large-scale applications.

12.
Int J Mol Sci ; 20(18)2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31514409

RESUMO

Hypertension is the most common modifiable risk factor for stroke, and understanding the underlying mechanisms of hypertension and hypertension-related stroke is crucial. 20-hydroxy-5, 8, 11, 14-eicosatetraenoic acid (20-HETE), which plays an important role in vasoconstriction, autoregulation, endothelial dysfunction, angiogenesis, inflammation, and blood-brain barrier integrity, has been linked to hypertension and stroke. 20-HETE can promote hypertension by potentiating the vascular response to vasoconstrictors; it also can reduce blood pressure by inhibition of sodium transport in the kidney. The production of 20-HETE is elevated after the onset of both ischemic and hemorrhagic strokes; on the other hand, subjects with genetic variants in CYP4F2 and CYP4A11 that reduce 20-HETE production are more susceptible to stroke. This review summarizes recent genetic variants in CYP4F2, and CYP4A11 influencing 20-HETE production and discusses the role of 20-HETE in hypertension and the susceptibility to the onset, progression, and prognosis of ischemic and hemorrhagic strokes.

13.
Platelets ; : 1-7, 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31556777

RESUMO

We investigated the comparative effects of smoking status on outcomes in older Chinese men receiving aspirin or clopidogrel monotherapy. This was a prospective observational study of outcomes in 668 men aged ≥ 60 years undergoing annual health examination in the Chinese People's Liberation Army General Hospital from March-April 2017. All patients received regular treatment with aspirin or clopidogrel. Platelet aggregation and phenotyping for rs762551 were measured in all patients. We recorded all major adverse cardiovascular and cerebrovascular events; namely, all-cause death, myocardial infarction, stroke, transient ischemic attack, and unstable angina. In the clopidogrel subgroup, homozygous carriers (AA) of the CYP1A2*1F gene (rs762551, 163C>A) appeared more frequently in smokers than in nonsmokers (45.6% vs 32.7%, p = .035). Adenosine diphosphate-induced platelet aggregation using light transmittance aggregometry was lower in smokers compared with nonsmokers (44.97 ± 20.05% vs 51.98 ± 19.38%, respectively; p = .0018). Smokers (n = 103) had a decreased risk of major adverse cardiovascular and cerebrovascular events, compared with nonsmokers [n = 159; hazard ratio, 0.466; 95% confidence interval: 0.262-0.829, p = .008]. In the aspirin subgroup, AA-induced platelet aggregation showed no significant difference regarding smoking vs nonsmoking status (30.90 ± 32.21 vs 29.78 ± 31.47, respectively; p = .771). However, we saw a significant increase in adverse clinical events in the smoking group (n = 148) compared with the nonsmoking group (n = 258; hazard ratio = 1.907, 95% confidence interval: 1.128-3.225; p = .016). In older Chinese men, active smokers benefitted from clopidogrel therapy compared with aspirin. Long-term cigarette smoking may contribute to increased variations in CYP1A2*1F, but the variations do not fully explain the smoking paradox.

14.
J Nat Prod ; 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31550154

RESUMO

Guided by 1H NMR spectroscopic experiments using the aromatic protons as probes, 11 macrocyclic diterpenes (1-11) were isolated from the aerial parts of Euphorbia helioscopia. Their full three-dimensional structures, including absolute configurations, were established unambiguously by spectroscopic analysis and single-crystal X-ray crystallographic experiments. Among the isolated compounds, compound 1 is the third member thus far of a rare class of Euphorbia diterpenes featuring an unusual 5/10 fused ring system, and 2-4 are new jatrophane diterpenes. Based on the NMR data of the jatrophane diterpenes obtained in this study as well as those with crystallographic structures reported in the literature, the correlations of the chemical shifts of the relevant carbons and the configurations of C-2, C-13, and C-14 of their flexible macrocyclic ring were considered. Moreover, the anti-inflammatory activities of 1-11 were investigated by monitoring their inhibitory effects on nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 cells. Compound 1 showed an IC50 of 7.4 ± 0.6 µM, which might be related to the regulation of the NF-κB signaling pathway by suppressing the translocation of the p65 subunit and the consequent reduction of IL-6 and TNF-α secretions.

15.
Nat Commun ; 10(1): 4130, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511532

RESUMO

Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.

16.
Dig Dis Sci ; 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31515723

RESUMO

BACKGROUND: In China, hyperlipidemia is the second major reason of acute pancreatitis. AIMS: Comparison of Scoring Systems in identification patients at risk for severe acute pancreatitis (SAP), pancreatic necrosis (PNec), and infected pancreatic necrosis (IPN) early in the course of hypertriglyceridemia-induced acute pancreatitis (HTG-AP). METHODS: Predictive accuracy of scoring systems was measured by the area under the receiver operating characteristic curve (AUC) in a retrospective study. Pairwise AUC comparisons were performed to calculate the difference between scoring systems. RESULTS: A total of 238 patients diagnosed with HTG-AP were included. Sixty patients (25.2%) were classified as SAP. Twenty-nine patients (12.2%) had evidence of PNec. Nine patients (3.8%) were diagnosed with IPN. One patient (0.4%) died during hospitalization. In predicting SAP in HTG-AP, the AUCs of APACHE-II, SOFA, SIRS, Ranson's, BISAP, and MMS were 0.77, 0.83, 0.73, 0.88, 0.83, and 0.85, respectively; in predicting PNec, were 0.75, 0.77, 0.75, 0.86, 0.80, and 0.75, respectively; and in predicting IPN, were 0.92, 0.86, 0.76, 0.85, 0.84, and 0.87, respectively. Pairwise AUC comparisons revealed that Ranson's, MMS, BISAP, and SOFA had higher accuracy than SIRS, Ranson's and MMS had higher accuracy than APACHE-II in predicting SAP; Ranson's had the same accuracy with BISAP, but higher than other four criteria in predicting PNec; APACHE-II had higher accuracy than SIRS in predicting IPN. CONCLUSIONS: APACHE-II had high performance in predicting IPN, and all other score systems had medium performance in predicting SAP, PNec, and IPN in HTG-AP. Each score has its merit and weakness; BISAP may be the best criterion in predicting severity and prognosis of HTG-AP.

17.
Microb Cell Fact ; 18(1): 160, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31547812

RESUMO

BACKGROUND: Alpha-Terpineol (α-Terpineol), a C10 monoterpenoid alcohol, is widely used in the cosmetic and pharmaceutical industries. Construction Saccharomyces cerevisiae cell factories for producing monoterpenes offers a promising means to substitute chemical synthesis or phytoextraction. RESULTS: α-Terpineol was produced by expressing the truncated α-Terpineol synthase (tVvTS) from Vitis vinifera in S. cerevisiae. The α-Terpineol titer was increased to 0.83 mg/L with overexpression of the rate-limiting genes tHMG1, IDI1 and ERG20F96W-N127W. A GSGSGSGSGS linker was applied to fuse ERG20F96W-N127W with tVvTS, and expressing the fusion protein increased the α-Terpineol production by 2.87-fold to 2.39 mg/L when compared with the parental strain. In addition, we found that farnesyl diphosphate (FPP) accumulation by down-regulation of ERG9 expression and deletion of LPP1 and DPP1 did not improve α-Terpineol production. Therefore, ERG9 was overexpressed and the α-Terpineol titer was further increased to 3.32 mg/L. The best α-Terpineol producing strain LCB08 was then used for batch and fed-batch fermentation in a 5 L bioreactor, and the production of α-Terpineol was ultimately improved to 21.88 mg/L. CONCLUSIONS: An efficient α-Terpineol production cell factory was constructed by engineering the S. cerevisiae mevalonate pathway, and the metabolic engineering strategies could also be applied to produce other valuable monoterpene compounds in yeast.


Assuntos
Cicloexenos/metabolismo , Engenharia Metabólica , Monoterpenos/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fosfatos de Poli-Isoprenil/metabolismo , Sesquiterpenos/metabolismo , Vitis/enzimologia , Vitis/genética
18.
Int J Surg ; 69: 124-131, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31386913

RESUMO

BACKGROUND: Tumor histology affects outcome after liver transplantation (LT) for hepatocellular carcinoma (HCC). This study explores the association between F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) and tumor histology in living donor liver transplantation (LDLT) recipients and their outcome. MATERIALS AND METHODS: Two hundred fifty-eight patients with primary liver tumors who underwent FDG-PET before LDLT were enrolled in this retrospective study. Unfavorable tumor histology was defined as primary liver tumor other than a well- or moderately differentiated HCC. Thirteen patients had unfavorable tumor histology, including 2 poorly differentiated HCC, 2 sarcomatoid HCC, 5 combined hepatocellular cholangiocarcinoma, 3 intrahepatic cholangiocarcinoma, and 1 hilar cholangiocarcinoma. RESULTS: FDG-PET positivity was significantly associated with unfavorable tumor histology (P < 0.001). Both FDG-PET positivity and unfavorable tumor histology were significant independent predictors of tumor recurrence and overall survival. In a subgroup analysis of patients with FDG-PET-positive tumors, unfavorable tumor histology was a significant independent predictor of tumor recurrence and overall survival. High FDG uptake (tumor to non-tumor uptake ratio ≥ 2) was a significant predictor of unfavorable tumor histology. Patients with high FDG uptake and/or unfavorable tumors had significantly higher 3-year cumulative recurrence rate (70.8% versus 26.2%, P = 0.004) and worse 3-year overall survival (34.1% versus 70.8%, P = 0.012) compared to those with low FDG uptake favorable tumors. CONCLUSIONS: The expression of FDG-PET is highly associated with histology of explanted HCC and predicts the recurrence. FDG-PET-positive tumors with high FDG uptake may be considered contraindication for LDLT due to high recurrence rate except when pathology proves favorable histology.

19.
J Am Heart Assoc ; 8(16): e013098, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31423869

RESUMO

Background We conducted a post hoc analysis of the SPS3 (Secondary Prevention of Small Subcortical Strokes) Trial to examine the association of chronic kidney disease (CKD) with recurrent stroke, and to assess whether baseline renal function modifies the effects of intensive systolic blood pressure control in patients with previous stroke. Methods and Results A total of 3020 patients with recent magnetic resonance imaging-defined symptomatic lacunar infarctions were randomized to a systolic blood pressure target of <130 mm Hg versus 130 to 149 mm Hg. Predefined primary outcomes were (all-recurrent) stroke and a composite of stroke, acute myocardial infarction, or all-cause death; secondary outcomes were acute myocardial infarction, all-cause death, and intracerebral hemorrhage individually. Among 3017 patients with baseline estimated glomerular filtration rate measurements, we evaluated, using Cox proportional hazards models, the association of CKD with recurrent stroke and effects of the blood pressure targets on outcomes using baseline estimated glomerular filtration rate both as a categorical and linear variable. Regardless of the randomized treatment, CKD at baseline was significantly associated with an increased risk of the primary cardiovascular composite outcome (hazard ratio, 1.7; 95% CI, 1.4-2.1), and all-recurrent stroke (1.5; 1.1-2.0). However, the effects of the lower systolic blood pressure intervention on the primary outcome were not influenced by baseline CKD status (P for interaction=0.62). Conclusions CKD increases the risk of recurrent stroke by 50% in patients with previous lacunar stroke. We found no definitive evidence that renal dysfunction modifies the effects of systolic blood pressure control in patients with previous stroke. Conclusive evidence for this will require adequately powered studies with moderate-to-advanced CKD. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059306.

20.
Int J Biol Macromol ; 141: 410-421, 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31465803

RESUMO

The medicinal plant Morinda officinalis How and its root have long been used in traditional medicines in China. The aims of the present study were to investigate the chemical composition and liver-protective effect of crude polysaccharides (MOP-100) from the processed root of Morinda officinalis against Concanavalin A (ConA)-induced liver damage in vivo and vitro. The processed root of the herbal medicine was extracted with water at 100 °C, then precipitated with ethanol, dialyzed and freeze-dried to obtain MOP-100. The molecular weight of MOP-100 was a wide distribution. However, the processed root was extracted consecutively at 60 °C and 100 °C to obtain two crude polysaccharides MOP-60 and MOP-60-100. MOP-60 mainly contained an inulin-type fructooligosaccharide with molecular weight of 2071 Da. MOP-100 significantly inhibited the infiltration of neutrophils and macrophages into liver, improved the hepatic injury induced by ConA in mice. It stimulated the proliferation of human liver LO2 cells and decreased the cell death induced by ConA. MOP-100 also significantly inhibited the HBeAg secretion of Hep2.5.5 hepatocytes in vitro. MOP-60 and MOP-60-100 both exhibited good activity of protecting hepatocytes against ConA-induced damage in vitro. These results suggested Morinda officinalis polysaccharides exert significant hepatoprotective effect, and it might be used for treatment of immune-mediated liver disease in the future.

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