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1.
J Cell Physiol ; 235(1): 408-420, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31230347

RESUMO

The atypical protein kinase C isoform ι (PKCι) is upregulated, which cooperates with mutated KRAS (mu-KRAS) to promote the development of pancreatic cancers. However, the exact role of PKCι in KRAS-mediated pancreatic tumorigenesis is not fully defined. In the present study, we demonstrate that mu-KRAS upregulates and activates PKCι, accompanied by dephosphorylation of large tumor suppressor (LATS), a key member of the growth-inhibiting Hippo signaling pathway. As a result, Yes-associated protein 1 (YAP1; a transcriptional coactivator) is dephosphorylated and translocates to the nucleus, which promotes transcription of downstream target genes to sustain the transformed growth of pancreatic cancer cells. In contrast, when PKCι is suppressed by the chemical inhibitor or small-hairpin RNA, the levels of phosphorylated LATS and YAP1 are elevated and YAP1 is excluded from the nucleus, which enhances the susceptibility of pancreatic cancer cells harboring mu-KRAS to apoptosis. These findings shed new light on the mechanisms underlying the pancreatic tumorigenesis initiated by mu-KRAS, and suggest that the PKCι-YAP1 signaling may potentially be therapeutically targeted for restricting the growth and inducing apoptosis in pancreatic tumors expressing mu-KRAS.

2.
Chemosphere ; 238: 124602, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31545211

RESUMO

Polybrominated diphenyl ethers (PBDEs) have been known to exhibit neurotoxicity in rats; however, the underlying mechanism remains unknown and there is no available intervention. In this study, we aimed to investigate the role of oxidative and nitrosative stress in the neurotoxicity in the cerebral cortex and primary neurons in rats following the BDE-153 treatment. Compared to the untreated group, BDE-153 treatment significantly induced the neurotoxic effects in rats, as manifested by the increased lactate dehydrogenase (LDH) activities and cell apoptosis rates, and the decreased neurotrophic factor contents and cholinergic enzyme activities in rats' cerebral cortices and primary neurons. When compared to the untreated group, the oxidative and nitrosative stress had occurred in the cerebral cortex or primary neurons in rats following the BDE-153 treatment, as manifested by the increments in levels of reactive oxygenspecies (ROS), malondialdehyde (MDA), nitric oxide (NO), and neuronal nitric oxide synthase (nNOS) mRNA and protein expressions, along with the decline in levels of superoxide dismutase (SOD) activity, glutathione (GSH) content, and peroxiredoxin I (Prx I) and Prx II mRNA and protein expressions. In addition, the ROS scavenger N-acetyl-l-cysteine (NAC) or NO scavenger NG-Nitro-l-arginine (L-NNA) significantly rescued the LDH leakage and cell survival, reversed the neurotrophin contents and cholinergic enzymes, mainly via regaining balance between oxidation/nitrosation and antioxidation. Overall, our findings suggested that oxidative and nitrosative stresses are involved in the neurotoxicity induced by BDE-153, and that the antioxidation is a potential targeted intervention.

3.
Vascul Pharmacol ; : 106613, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31678650

RESUMO

Metformin (Met) can improve atherosclerosis (As). Abnormal endothelin receptors [including endothelin type A (ETA) or type B (ETB) receptor] in vascular smooth muscle cells (VSMCs) are involved in As. Hyperhomocysteinemia (HHcy) is an independent risk factor for As. The present study was designed to test our hypothesis that Met inhibits the upregulation of endothelin receptors induced by homocysteine (Hcy) in VSMCs. Rat superior mesenteric artery (SMA) without endothelium, as an in vitro model, was cultured in serum-free medium for 24 h in the presence of Hcy with or without Met or nicotinamide (Nic). In vivo, rats received subcutaneous injections of Hcy in the presence or absence of Met or Nic for 3 weeks. Levels of protein expression were determined by Western blotting. The contractile responses to sarafotoxin 6c (an ETB receptor agonist) or ET-1 (an ETA/ ETB receptor agonist) were studied using a sensitive myograph. The blood pressure of rats was measured using a noninvasive tail-cuff plethysmography method. The results showed that Met could significantly inhibit the Hcy-induced upregulation of endothelin receptors (including ETA and ETB receptor) protein expression and endothelin receptor-mediated vasoconstriction, and it recovered the Hcy-induced decrease in silent information regulator 1 (Sirt1) in a dosage-dependent manner in SMA. However, Nic (a Sirt1 inhibitor) recovered the levels of Met-inhibited endothelin receptors and acetylated p65. Furthermore, the in vivo results showed that Met not only significantly the inhibited HHcy-induced upregulation of endothelin receptors and acetylated p65 but also recovered the HHcy-induced decrease in Sirt1 in a dosage-dependent manner in SMA. In addition, Met significantly inhibited the HHcy-induced blood pressure elevation. However, these effects were reverted by Nic. In conclusion, these data demonstrated that Met inhibited the Hcy-induced increase in endothelin receptor expression by activating Sirt1 and then inhibiting NF-κB in VSMCs. These findings may provide insights into the mechanism underlying of Met-treated cardiovascular diseases induced by Hcy.

4.
Anat Histol Embryol ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31571240

RESUMO

The distribution of glucagon-like peptide 1 (GLP-1)-positive cells in digestive tracts and pancreases of aquatic vertebrates was investigated by immunohistochemical staining method. The results suggested that GLP-1-positive cells were distributed in the columnar mucous epithelium and tubular glands of lamina propria in the digestive system. However, GLP-1-positive cells were also found in subepithelial lamina propria of the mucosae and muscularis in each segment of the digestive tract of Rana nigromaculata. The distribution densities of these cells reached peaks in the stomachs, and the middle or end segments of small intestines of Chinese softshell turtle, Bufo gargarizans, R. nigromaculata and catfish, and there was the third distribution density peak in the rectum of catfish. The total amount or overall density of GLP-1-positive cells varied a lot in the digestive tracts of different animal species. The distribution density was relatively low in the digestive tract of chub and reached the maximum in the digestive tracts of snakehead and catfish, but no GLP-1-positive cells were found in the digestive tract of bighead carp. GLP-1-positive cells were densely distributed in the pancreases of Chinese softshell turtle, B. gargarizans and R. nigromaculata. These cells spread over the superficial layers of islets or scattered in exocrine pancreas in the pancreas of B. gargarizans, spread in the endocrine cells or scattered in the pancreas of Chinese softshell turtle, scattered in the pancreas of R. nigromaculata and distributed in the superficial layers of islets in the pancreas of catfish.

5.
Anticancer Drugs ; 30(10): 1013-1021, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31609763

RESUMO

Antisense non-coding RNA in the INK4A locus (ANRIL) has been recognized as a cancer-related lncRNA in hepatocellular carcinoma previously. This study aimed to reveal the functional effects and mechanisms of ANRIL on hepatocellular carcinoma cells in vitro. The expression of ANRIL in hepatocellular carcinoma cell lines (MHCC97 and Li-7) and non-tumourigenic liver cell line THLE-3 was detected by qRT-PCR. The expression of ANRIL, miR-144 and PBX3 in hepatocellular carcinoma cells was altered simultaneously or respectively by vector/oligonucleotide transfection. Then, cell viability, migration, invasion, apoptotic cell rate, protein expression of apoptosis-related factors were assessed. The correlation between ANRIL, miR-144 and PBX3 was explored. ANRIL was highly expressed in MHCC97 and Li-7 cells when compared to THLE-3 cells. ANRIL overexpression promoted cell viability, migration, invasion and suppressed apoptosis of MHCC97 and Li-7 cells. ANRIL negatively regulated miR-144, and oncogenic effects of ANRIL were attenuated when miR-144 was overexpressed. PBX3 was a direct target of miR-144. miR-144 overexpression blocked PI3K/AKT and JAK/STAT signalling pathways via targeting PBX3. Our data documented that ANRIL promoted hepatocellular carcinoma cells growth, migration and invasion. One of the possible mechanisms responsible for the tumour-promoting actions is that ANRIL sponging miR-144 to derepress PBX3.

6.
Clin Neurol Neurosurg ; 186: 105428, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31581028

RESUMO

The treatment efficacy of galcanezumab for migraine remained controversial. We conducted a systematic review and meta-analysis to explore the influence of galcanezumab versus placebo on the treatment of migraine. We searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through October 2018 for randomized controlled trials (RCTs) assessing the effect of galcanezumab versus placebo for patients with migraine. This meta-analysis was performed using the random-effect model. Six RCTs were included in the meta-analysis. Overall, compared with control group for migraine patients, galcanezumab resulted in greater overall mean reduction in the number of monthly migraine headache day (MHD) (P < 0.05). In contrast, galcanezumab was associated with increased adverse events (risk ratio (RR) = 1.08; 95% CI = 1.01-1.15; P = 0.02), but with no significant impact on serious adverse events between two groups (RR = 2.0; 95% CI = 0.95-4.21; P = 0.07).Galcanezumab showed favorable promotion for the preventive treatment of migraine patients.

7.
Spectrochim Acta A Mol Biomol Spectrosc ; 227: 117662, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31654845

RESUMO

Exploring the protein-nanomaterials interactions is the topic of high relevance for the future applications of new nanomaterials in biological system. Herein, the binding mechanism of bovine serum albumin(BSA) and bovine hemoglobin(BHB) with two-dimensional black phosphorus nanosheets (BP NSs) was reported. Muti-spectral results showed that the combination of BP NPs with protein resulted in the fluorescence quenching of BSA and BHB and induced the extension of the protein peptide chain by van der Waals forces, hydrophobic forces, and electron-transfer forces. Both BSA and BHB retain their structure in α-helix form. The induced circular dichroism (ICD) spectral results showed that the presence of BP NPs partly destroyed the binding domain of BHB with bilirubin and altered the tertiary structure of BHB by BP NPs binding.

8.
Aging (Albany NY) ; 11(17): 6930-6940, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31479417

RESUMO

Backgroud: Bladder cancer (BLCA) is one of the most fatal types of cancer worldwide. However, there are limited methods for us to provide a prognostic prediction of BLCA patients. Therefore, we aimed at developing a lncRNA signature to improve the prognosis prediction of BLCA. RESULTS: An eight-lncRNA signature was significantly associated with recurrence free survival in BLCA patients from both discovery and validation groups. Furthermore, genes involved in the signature were enriched in extracellular matrix organization pathway. Finally, functional experiments demonstrated that six out of the eight lncRNAs significantly regulated the invasion of BLCA cells. METHOD: A total of 343 BLCA patients from The Cancer Genome Atlas (TCGA) were employed and randomly divided into training (n=172) and validating (n=171) groups. The lncRNA expression profiles of BLCA patients were screened and a risk-score formula were created and validated according to the Cox regression analysis. Next, WGCNA method was employed to cluster genes that highly correlated with the risk scores based on the profiling data of TCGA dataset and transwell assay was also performed to further investigate the role of these lncRNAs. CONCLUSIONS: Our results suggested that the eight-lncRNA signature was a candidate prognostic biomarker for predicting tumor recurrence of patients with BLCA.

9.
J Hazard Mater ; 383: 121160, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31518812

RESUMO

The application of current soil quality standards based on total arsenic (As) fails to assess the ecological risks of soil arsenic or to ensure the safety of crops and foods. In this study, bioavailable arsenic instead of total arsenic was applied to improve predictive models for arsenic transfer from soil to wheat (Triticum turgidum L.). The stepwise multiple-linear regression analysis showed that bioavailable arsenic and amorphous iron oxides (FeOX) were the two most important factors contributing to arsenic accumulation in wheat grain, with the explained percentage of variation being up to 82%. Compared with the bioavailable arsenic extracted by NH4H2PO4, bioavailable arsenic extracted by HNO3 from soils generated better predictions of the amount of arsenic in grain. The best reliable model was log[Asgrain] = 0.917 log[HNO3-As] - 0.452 log[FeOX] - 1.507 (R2 = 0.82, P <  0.001). Consistently, bioavailable arsenic and FeOX were also the key factors to predict arsenic accumulation in wheat straw, leaves and spikes. Our prediction models was successfully verified for three independent soils. Our results highlight the role of soil bioavailable heavy metals in predicting their transfer in soil-plant systems and can be used to improve existing Chinese soil quality standards.

10.
Int J Biol Macromol ; 139: 521-530, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31377297

RESUMO

Chitosan-1-(mercaptomethyl)-cyclopropane acetic acid (CS-MCA) copolymer was synthesized by amino linkage. The obtained copolymer was characterized by FTIR, 1H NMR, XRD, TGA and SEM. Porous and reticulate morphologies were found on the CS-MCA surface. The effects of pH on the rheological properties of CS-MCA were investigated. On the one hand, the apparent viscosity of CS-MCA indicated a shear-thinning behavior. The graft of MCA enhanced the moduli and the maximum elastic properties were observed at pH = 7.00. The addition of dithiothreitol reduced the viscosity and modulus of CS-MCA hydrogel, and the gelation time, temperature and frequency were obtained in dynamic oscillatory tests. The antibacterial effect of CS-MCA against E. coli was investigated for the inhibition zone and bacterial growth curve. These results showed that CS-MCA had better antibacterial ability than chitosan without modification. Therefore, the rheological behavior and functional activities can be applied for the hydrocolloid gels in food and pharmaceutical applications.

11.
J Photochem Photobiol B ; 198: 111578, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31408842

RESUMO

In recent years, biological nanomedicine-based biomaterials have an extreme attention for biomedical uses, herein we examined a novel kind advance of photoluminescent Graphene quandum dots encapsulated mesoporous nanoparticles (GND@MSNs) encapsulated by well-known anticancer drugs Doxorubicin (DOX) and Cyclosporin (CsA) for lung carcinoma. Electron microscopic technique exhibit the nanostructure and spherical morphology of GND@MSNs+DOX+CsA with mean size ≈110 nm. Moreover, Dynamic Light Scattering (DLS) exposed that blended GND@MSNs+DOX+CsA nanoparticles were highly stable with extremely negatively charged nanoparticles. Raman investigation was done on the all naturally dynamic nanoparticles containing shed graphene to survey the blend condition of the graphene inside the silica mesoporous nanoparticles. GND@MSNs+DOX+CsA provided an outstanding anti-cancer efficiency against the lung cancer cell lines (i.e., A549 and HEL-299). MTT assay monitored that GND@MSNs, GND@MSNs+DOX and GND@MSNs+DOX+CsA have a robust toxicity behaviour on the A549 and HEL-299 model lung cancer cell lines. Additionally, investigation of the cell death was found on AO-EB, Hoechst 33452 staining and flowcytometry techniques. Furthermore, the DNA damage were confirmed by cell cycle arrest and comet assay. Hence, we suggesting that these GND@MSNs+DOX+CsA could be applied as auspicious drug vesicles for novel lung cancer therapeutic potential and new openings to solve the complexity of lung cancer in the care of cancer patients.

12.
Mol Med Rep ; 20(4): 3371-3378, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31432138

RESUMO

The present study aimed to explore the effect of the long non­coding RNA TP73 antisense RNA 1 (TP73­AS1) on cervical cancer progression. Cervical cancer and adjacent tissues were collected from 56 patients and assessed. In addition, HeLa and CaSki cells were transfected with various plasmids, inhibitors and corresponding controls, and then Cell Counting Kit­8 and Transwell assays were used to detect the cell proliferation, migration and invasion abilities. Luciferase reporter gene assay was also performed in HeLa cells. Reverse transcription­quantitative polymerase chain reaction (RT­qPCR) was used to investigate TP73­AS1, microRNA­607 (miR­607) and cyclin D2 (CCND2) gene expression, while CCND2 protein expression was determined by western blot analysis. The results revealed that the TP73­AS1 level was upregulated in cervical cancer tissues (P<0.05) and predicted a poor 5­year overall survival (P<0.05). HeLa and CaSki cells transfected with siTP73­AS1 exhibited reduced proliferation, migration and invasion abilities when compared with those in the siNC group (P<0.05). Furthermore, miR­607 was found to be negatively regulated by TP73­AS1, while CCND2 was negatively regulated by miR­607. HeLa and CaSki cells transfected with siTP73­AS1 exhibited lower CCND2 mRNA and protein expression levels compared with the siNC and siTP73­AS1 + miR­inhibitor groups (P<0.05). Compared with the siNC and siTP73­AS1 + CCND2 overexpression groups, siTP73­AS1­transfected HeLa and CaSki cells had decreased proliferation, migration and invasion abilities (P<0.05). In conclusion, the findings suggested that upregulation of TP73­AS1 promoted cervical cancer progression by promoting CCND2 via the suppression of miR­607 expression.

13.
Cancer Biomark ; 26(2): 203-207, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31403942

RESUMO

OBJECTIVE: To investigate the diagnostic and prognostic values of long non-coding RNA H19 (H19) in patients with papillary thyroid carcinoma (PTC). METHODS: This retrospective, nonrandomised study included 410 patients with PTC and 89 patients with benign thyroid nodes (BTN)who underwent standard total thyroidectomy. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect H19 expression in these tissues. The relationship between H19 expression and the patients' clinicopathological factors, including histopathological characteristics of the tumour, diagnosis and prognosis was explored. RESULTS: Expression of H19 was lower in the PTC tissues (1.259 ± 1.15) compared to the BNT tissues (2.8347 ± 2.176) (p= 0.001). Low expression of H19 was associated with patient's age, tumor size, extrathyroid extension, pathological lateral node metastasis (pN1b), histological aggressive type and poorer disease-free survival (p< 0.0001). The sensitivity for distinguishing PTC from benign was 81.3%. H19 was found to be an independent risk factor for extrathyroidal extension, lymph node metastasis. CONCLUSIONS: H19 may serve as a potential predictor of poor prognoses in patients with PTC.

14.
Clin Epigenetics ; 11(1): 128, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31464656

RESUMO

BACKGROUND: Breastfeeding is protective against many long-term diseases, yet the mechanisms involved are unknown. Leptin gene (LEP) is reported to be associated with body mass index (BMI). On the other hand, breastfeeding duration has been found to be associated with DNA methylation (DNAm) of the LEP gene. Therefore, epigenetic regulation of LEP may represent the mechanism underlying the protective effect of breastfeeding duration against obesity. METHODS: In the Isle of Wight Birth Cohort, peripheral blood DNAm at 23 cytosine-phosphate-guanine sites (CpGs) in the LEP locus in 10-year-old (n = 297) samples and 16 CpGs in 18-year-old (n = 305) samples, were generated using the Illumina Infinium MethylationEPIC and HumanMethylation450 Beadchips respectively and tested for association with breastfeeding duration (total and exclusive) using linear regression. To explore the association between breastfeeding durations and genome-wide DNAm, epigenome-wide association studies (EWASs) and differential methylation region (DMR) analyses were performed. BMI trajectories spanning the first 18 years of life were used as the outcome to test the association with breastfeeding duration (exposure) using multi-nominal logistic regression. Mediation analysis was performed for significant CpG sites. RESULTS: Both total and exclusive breastfeeding duration were associated with DNAm at four LEP CpG sites at 10 years (P value < 0.05), and not at 18 years. Though no association was observed between breastfeeding duration and genome-wide DNAm, DMR analyses identified five significant differentially methylated regions (Sidak adjusted P value < 0.05). Breastfeeding duration was also associated with the early transient overweight trajectory. Furthermore, DNAm of LEP was associated with this trajectory at one CpG site and early persistent obesity at another, though mediation analysis was not significant. CONCLUSIONS: Breastfeeding duration is associated with LEP methylation at age 10 years and BMI trajectory. LEP DNAm is also significantly associated with BMI trajectories throughout childhood, though sample sizes were small. However, mediation analysis did not demonstrate that DNAm of LEP explained the protective effect of breastfeeding against childhood obesity.

15.
Int J Immunopathol Pharmacol ; 33: 2058738419869489, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31462112

RESUMO

Polysaccharides from Ganoderma lucidum have been demonstrated to possess diverse biological activities. Despite lots of studies on the biological activities of Ganoderma lucidum polysaccharide (GLP), little is known regarding the medicinal potential of low-molecular weight enzymatically hydrolyzed Ganoderma lucidum polysaccharide (EGLP). EGLP was prepared by enzymatic degradation and its potential effects in U14 cervical tumor-bearing mice were evaluated. Both GLP and EGLP delayed tumor growth of the tumor xenograft. The EGLP was superior to native polysaccharide. Moreover, EGLP treatment could effectively protect the immune organs of U14 cervical carcinoma-bearing mice. In addition, the EGLP treatment ameliorated oxidative stress as compared with cyclophosphamide (CTX). Compared with the MC group, the expression of Bcl-2 and COX-2 was obviously decreased by EGLP treatment, whereas the expression of Bax and cleaved caspase-3 was obviously increased. These results indicated that EGLP showed stronger antitumor activity with lower toxic effects and had the potential to be a novel antitumor agent.

16.
BMJ Open ; 9(7): e028429, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31340966

RESUMO

OBJECTIVES: The Depression Stigma Scale (DSS) is commonly used to assess depression stigma in the general population and in people with depression. The DSS includes two 9-item subscales assumed to measure personal depression stigma (ie, personal perceptions of depression) and perceived depression stigma (ie, perceptions of how others perceive depression). The aim of the present study was to examine its psychometric properties in terms of validity and reliability in Chinese cancer patients. DESIGN: A cross-sectional study design. PARTICIPANTS AND SETTINGS: This study focused on 301 Chinese cancer patients recruited from two hospitals in Xi'an, China. METHODS: Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to assess the factor structure. Internal consistency was assessed using Cronbach's alpha. To examine concurrent validity, symptoms of depression were used as the criterion. RESULTS: For each subscale of the DSS (ie, personal and perceived depression stigma), the EFA and CFA confirmed a two-factor structure: weak-not-sick (ie, perceiving that depression is not a real illness, but rather a sign of weakness) and discrimination (ie, perceiving that depressed people are discriminated against). The Cronbach's alphas were adequate, ranging from 0.70 to 0.80. Symptoms of depression were positively but weakly correlated to personal and perceived depression stigma. CONCLUSIONS: The DSS appeared to show satisfactory psychometric properties in our sample of cancer patients. Both personal depression stigma and perceived depression stigma subscales consisted of two underlying aspects.

17.
Curr Med Sci ; 39(4): 576-581, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31346993

RESUMO

The present analysis aims to investigate the prevalence of thyroid nodules in type 2 diabetes mellitus (T2DM) population. We searched PubMed, EMBASE, and Web of Science from inception to the March 1, 2018. The studies were selected to estimate the prevalence of thyroid nodules in T2DM subjects and to compare the prevalence of thyroid nodules in different glucose tolerance status. The random effects model was used, and the outcome was presented as a pooled prevalence proportion with 95% confidence interval (95% CI) or a summary odds ratio (OR) with 95% CI. In the end, 9 studies met the inclusion criteria and were included in the analysis. The pooled prevalence of thyroid nodules was 60% (95% CI: 0.52, 0.68) for T2DM 2 diabetes patients, 50% (95% CI: 0.48, 0.51) for pre-diabetes, and 43% (95% CI: 0.34, 0.52) for normal glucose tolerance population. Compared with patients without diabetes, diabetes subjects are more likely to develop thyroid nodules, adjusted OR for thyroid nodule was 1.78 (95% CI: 1.25, 2.55). Insulin resistance might be involved in thyroid nodule development.

18.
Abdom Radiol (NY) ; 44(9): 2978-2987, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31327039

RESUMO

PURPOSE: The aim of this study was to build an appropriate diagnostic model for predicting pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC), by combining magnetic resonance imaging (MRI) parameters with clinical factors. METHODS: Eighty-four patients with LARC who underwent MR examination before and after nCRT were enrolled in this study. MRI parameters including cylindrical approximated tumor volume (CATV) and relative signal intensity of tumor (rT2wSI) were measured; corresponding reduction rates (RR) were calculated; and MR tumor regression grade (mrTRG) and other conventional MRI parameters were assessed. Logistic regression with lasso regularization was performed and the appropriate prediction model for pCR was built up. An external cohort of thirty-six patients was used as the validation group for testing the model. Receiver-operating characteristic (ROC) analysis was used to assess the diagnostic performance. RESULTS: In the development and the validation group, 17 patients (20.2%) and 11 patients (30.6%), respectively, achieved pCR. Two CATV-related parameters (CATVpost, which is the CATV measured after nCRT and CATVRR), one rT2wSI-related parameter (rT2wSIRR), and mrTRG were the most important parameters for predicting pCR and were retained in the diagnostic model. In the development group, the area under the receiver-operating characteristic curve (AUC) for predicting pCR is 0.88 [95% confidence interval (CI) 0.78-0.97, p < 0.001], with a sensitivity of 82.4% and a specificity of 83.6%. In the validation group, the AUC is 0.84 (95% CI 0.70-0.98, p = 0.001), with a sensitivity of 81.8% and a specificity of 76.0%. CONCLUSION: A diagnostic model including CATVpost, CATVRR, rT2wSIRR, and mrTRG was useful for predicting pCR after nCRT in patients with LARC and may be used as an effective organ-preservation strategy.

19.
Biomed Chromatogr ; 33(11): e4648, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31301083

RESUMO

Shejin-liyan Granule (SJLY) is an effective traditional Chinese prescription medicine for the treatment of acute pharyngitis. In this study, a selective and convenient HPLC-MS/MS method was developed and validated for the simultaneous determination of the following eight constituents in the plasma: galuteolin, tectoridin, tectorigenin, iridin, irigenin, irisflorentin, arctiin and arctigenin. The plasma samples were prepared by a protein precipitation method using acetonitrile, and analysis was carried out on a C18 column using a gradient elution at a flow rate of 0.3 mL/min. The concentration of these analytes was quantified in the positive ion and multiple reaction monitoring modes. The method was validated for selectivity, linearity, accuracy, precision, recovery, matrix effect and sample stability. The obtained results were well within the acceptable limits. The established method was then successfully applied to study the pharmacokinetic profiles of the multiple constituents of Shejin-liyan Granule. According to the area under the curve and maximum concentration data, tectorigenin exhibited the highest exposure followed by arctigenin, irigenin, arctiin and irisflorentin. The concentrations of galuteolin, tectoridin and iridin were low, and a complete concentration-time curve could not be plotted. This research provides useful information for understanding the pharmacokinetics of Shejin-liyan Granule.

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