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1.
Artigo em Inglês | MEDLINE | ID: mdl-32146835

RESUMO

BACKGROUND/PURPOSE: Colorectal cancer (CRC) is one of the most common malignant tumours and is associated with a high mortality rate due to the lack of specific biomarkers available for early diagnosis, targeted therapies and prognostic surveillance. In the present study, we investigated the function of Numb and its underlying mechanism in colorectal cancer. METHODS: Immunohistochemical staining and clinicopathological analysis were used to assess the expression of Numb and its clinical significance in patients with colorectal cancer. Quantitative real-time polymerase chain reaction, cell proliferation, western blot, wound healing, Transwell and TOP/FOP flash reporter assays were used to investigate the function of Numb and its underlying mechanism in colorectal cancer. RESULTS: Numb expression was down-regulated and negatively correlated with the depth of invasion, tumour size, metastasis, TNM stage and EMT markers in colorectal cancer specimens. Numb negatively regulates the EMT, proliferation, invasion, migration and the Wnt signalling pathway in vitro, as well as tumour growth and metastasis in vivo. Furthermore, activation of the Wnt signalling pathway by Wnt-3A negated the effect of Numb overexpression, while inhibition of the Wnt signalling pathway by IWR-1 impaired the effect of the Numb knockdown on the EMT. CONCLUSION: Numb downregulation is a common event in patients with colorectal cancer and is closely correlated with cancer progression and a poor prognosis. Numb functions as a tumour suppressor in colorectal cancer, and its tumour suppressor function is mediated by negative regulation of the EMT through the Wnt signalling pathway.

2.
Clin Infect Dis ; 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32161968

RESUMO

BACKGROUND: A novel coronavirus (2019-nCoV) has raised world concern since it emerged in Wuhan Hubei China in December, 2019. The infection may result into severe pneumonia with clusters illness onsets. Its impacts on public health make it paramount to clarify the clinical features with other pneumonias. METHODS: Nineteen 2019-nCoV pneumonia (NCOVID-19) and fifteen other pneumonia patients (NON-NCOVID-19) in out of Hubei places were involved in this study. Both NCOVID-19 and NON-NCOVID-19 patients were confirmed to be infected in throat swabs or/and sputa with or without 2019-nCoV by real-time RT-PCR. We analyzed the demographic, epidemiological, clinical, and radiological features from those patients, and compared the difference between NCOVID-19 and NON-NCOVID-19. RESULTS: All patients had a history of exposure to confirmed case of 2019-nCoV or travel to Hubei before illness. The median duration, respectively, was 8 (IQR:6~11) and 5 (IQR:4~11) days from exposure to onset in NCOVID-19 and NON-NCOVID-19. The clinical symptoms were similar between NCOVID-19 and NON-NCOVID-19. The most common symptoms were fever and cough. Fifteen (78.95%) NCOVID-19 but 4 (26.67%) NON-NCOVID-19 patients had bilateral involvement while 17 (89.47%) NCOVID-19 but 1 (6.67%) NON-NCOVID-19 patients had multiple mottling and ground-glass opacity of chest CT images. Compared to NON-NCOVID-19, NCOVID-19 present remarkably more abnormal laboratory tests including AST, ALT, γ-GT, LDH and α-HBDH. CONCLUSION: The 2019-nCoV infection caused similar onsets to other pneumonias. CT scan may be a reliable test for screening NCOVID-19 cases. Liver function damage is more frequent in NCOVID-19 than NON-NCOVID-19 patients. LDH and α-HBDH may be considerable markers for evaluation of NCOVID-19.

3.
Curr Neurovasc Res ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32056526

RESUMO

OBJECTIVE: The effects of mesenchymal stem cell (MSC)-derived exosomes on brain microvascular endothelial cells under oxygen-glucose deprivation (OGD), which mimics cells in deep hypothermic circulatory arrest (DHCA) in vitro, are yet to be studied. METHODS: MSCs were co-cultured with primary rat brain endothelial cells, which were then exposed to OGD. Cell viability, apoptosis, the inflammatory factors (IL-1ß, IL-6, and TNF-α), and the activation of inflammation-associated TLR4-mediated pyroptosis and the NF-κB signaling pathway were determined. Furthermore, exosomes derived from MSCs were isolated and incubated with endothelial cells to investigate whether the effect of MSCs is associated with MSC-derived exosomes. Apoptosis, cell viability, and the inflammatory response were also analyzed in OGD-induced endothelial cells incubated with MSC-derived exosomes. RESULTS: OGD treatment promoted endothelial cell apoptosis, induced the release of inflammatory factors IL-1ß, IL-6, and TNF-α, and inhibited cell viability. Western blot analysis showed that OGD treatment induced TLR4, and NF-κB p65 subunit phosphorylation and caspase-1 upregulation, while co-culture with MSCs could reduce the effect of OGD treatment on endothelial cells. As expected, the effect of MSC-derived exosomes on OGD-treated endothelial cells was similar to that of MSCs. MSC-derived exosomes alleviated the OGD-induced decrease in the viability of endothelial cells, and increased levels of apoptosis, inflammatory factors, and the activation of inflammatory and inflammatory focal pathways. CONCLUSION: Both MSCs and MSC-derived exosomes attenuated OGD-induced rat primary brain endothelial cell injury. These findings suggest that at least some of the protective effects of MSCs on endothelial cells are mediated by MSC-derived exosomes.

4.
Phys Rev Lett ; 124(3): 033401, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-32031827

RESUMO

We observe thermalization in the production of a degenerate Fermi gas of polar ^{40}K^{87}Rb molecules. By measuring the atom-dimer elastic scattering cross section near the Feshbach resonance, we show that Feshbach molecules rapidly reach thermal equilibrium with both parent atomic species. Equilibrium is essentially maintained through coherent transfer to the ground state. Sub-Poissonian density fluctuations in Feshbach and ground-state molecules are measured, giving an independent characterization of degeneracy and directly probing the molecular Fermi-Dirac distribution.

5.
Chin Med J (Engl) ; (6): 664-669, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32068603

RESUMO

BACKGROUND: Proliferative diabetic retinopathy (PDR) is a progressive stage of diabetic retinopathy featured by the formation of neovascular and proliferative membrane. Vascular endothelial growth factor (VEGF) acts as a pivot factor in the development of neovascularization. This study was to investigate the changes of intravitreal VEGF concentrations of severe PDR after intravitreal injection of conbercept (IVC) and its potential advantages to the following vitrectomy. METHODS: This was a prospective, interventional, randomized controlled study. Sixty eyes (60 patients) with severe PDR and 20 eyes from 20 patients with rhegmatogenous retinal detachment complicated with proliferative vitreoretinopathy were enrolled in this study. PDR eyes were randomly assigned to three groups by sortation randomization method with 20 eyes in each based on the interval of preoperative IVC (group A: 7 days, group B: 14 days, group C: non-IVC). Another 20 eyes without diabetes were enrolled as the non-diabetic control group (group D), receiving PPV directly. Vitreous specimens of all 80 patients were collected and evaluated afterwards. The intravitreal VEGF concentration of the four groups, and the total surgical time and the intraoperative bleeding rate of the PDR groups were recorded. RESULTS: The mean intravitreal VEGF concentrations of groups A-D were 66.6 ±â€Š43.3, 93.1 ±â€Š52.3, 161.4 ±â€Š106.1 and 1.8 ±â€Š1.2 pg/mL, respectively. It increased significantly in PDR patients (groups A, B and C) (P = 0.002, <0.001, and <0.001, respectively). PDR patients with preoperative IVC (groups A and B) presented significantly lower VEGF concentrations (P < 0.001 and 0.001), intraoperative bleeding rates (P = 0.004) and total surgical time (P < 0.001, P = 0.003) compared with group C. No statistical differences were presented between groups A and B on the three parameters. CONCLUSION: Seven days and 14 days of preoperative IVC are equally efficient and safe for the vitrectomy of severe PDR patients through decreasing vitreous VEGF concentrations, intraoperative bleeding rate and total surgical times.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32105831

RESUMO

We aimed to investigate the frequency, risk factors, and outcome of active tuberculosis (TB) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This retrospective, nested, case-control study reviewed data from 6236 patients who received allo-HSCT from January 2008 to December 2018 at a single center; 33 patients (0.5%) with active TB and 99 controls without active TB after allo-HSCT were identified. We performed propensity score matching by randomly selecting 3 controls for each identified active TB patient according to the time of transplantation and follow-up period. History of pretransplant active TB previously treated and inactive at time of transplantation (P < .001) was an independent risk factor. No significant differences in overall survival (P = .342), nonrelapse mortality (P = .497), or incidence of relapse (P = .807) were found. Thirty (90.9%) were treated with 4-drug (isoniazid, rifampicin/three rifapentine, pyrazinamide, and ethambutol) or 3-drug combination first-line therapy, with a response rate of 76.7%. Twenty-six (78.8%) patients were treated with first-line and second-line combined therapy, and the response rate was 76.9%. Five (15.2%) patients developed hepatotoxicity. In conclusion, history of pretransplant active TB previously treated and inactive at time of transplantation was an independent risk factor of active TB after allo-HSCT. No significant differences in prognosis between the TB and control groups were found. More studies are needed to help develop standardized therapeutic strategies for patients with post-transplant TB.

7.
Phys Rev Lett ; 124(5): 053201, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32083904

RESUMO

Cold molecules provide an excellent platform for quantum information, cold chemistry, and precision measurement. Certain molecules have enhanced sensitivity to beyond standard model physics, such as the electron's electric dipole moment (eEDM). Molecular ions are easily trappable and are therefore particularly attractive for precision measurements where sensitivity scales with interrogation time. Here, we demonstrate a spin precession measurement with second-scale coherence at the quantum projection noise (QPN) limit with hundreds of trapped molecular ions, chosen for their sensitivity to the eEDM rather than their amenability to state control and readout. Orientation-resolved resonant photodissociation allows us to simultaneously measure two quantum states with opposite eEDM sensitivity, reaching the QPN limit and fully exploiting the high count rate and long coherence.

8.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(2): 101-105, 2020 Feb 10.
Artigo em Chinês | MEDLINE | ID: mdl-32034731

RESUMO

OBJECTIVE: To explore the clinical feature, genetic variant and clinical outcome of patients with cblA-type methylmalonic acidemia (MMA). METHODS: Clinical manifestations, therapeutic schedule and prognosis of 12 patients with cblA type MMA were analyzed. MMAA gene variants were analyzed for all patients and their parents. RESULTS: Vomiting, dyspnea and drowsiness were the major clinical features of cblA-type MMA. Eleven patients were vitamin B12-responsive. After treatment, the blood level of propionylcarnitine, ratio of propionylcarnitine/acetylcarnitine, urine level of methylmalonic acid and methylcitric acid have decreased significantly (P< 0.05). Follow-up study showed that 8 patients (66.7%) had normal development, while the rest (33.3%) remained to have various level of mental or movement delay. Fourteen MMAA gene variants were detected, with c.365T>C (p.L122P) being the most common (29.2%). Six novel variants, including c.54delA (p.A19Hfs*43), c.275G>A (p.G92V), c.456delT (p.G153Vfs*8), c.667dupA (p.T223Nfs*4), c.1114C>T (p.Q372X) and c.1137_1138delCA (p.F379Lfs*27) were found. CONCLUSION: The main clinical manifestations of patients with cblA-type of MMA include vomiting, dyspnea and drowsiness. Most patients are vitamin B12-responsive. c.365T>C is a potential hot spot variant of MMAA gene in China.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos , Sequência de Bases , China , Seguimentos , Humanos , Vitamina B 12
9.
Artigo em Inglês | MEDLINE | ID: mdl-32032407

RESUMO

This meta-analysis aimed to evaluate the clinical effectiveness of autologous platelet concentrates (APC) + coronally advanced flap (CAF) (Group A) compared with connective tissue graft (CTG) + CAF (Group B), and CAF alone (Group C), in patients with Miller Class I or II gingival recessions. Relevant articles published before December 2018 were retrieved electronically without date or language restriction and screened according to inclusion criteria. Quantitative meta-analysis was conducted comparing the groups. The inverse variance method was applied in fixed or random effects models according to heterogeneity. Sixteen randomized controlled trials were included. Root coverage (RC), clinical attachment level (CAL), gingival thickness (GT), and probing depth (PD) did not differ significantly between Groups A and B. The keratinized gingival width (KGW) of Group A was significantly less than that of Group B. The RC and GT of Group A were significantly greater than that in Group C. CAL and PD for Group A were lower than for Group C. KGW for Group A did not differ significantly from that of Group C. The results suggested that APC + CAF represents a promising alternative for root coverage for Miller Class I and II gingival recession defects. Nevertheless, CTG + CAF exhibits superior outcomes in terms of KGW. Hence, in scenarios lacking keratinized gingiva (Miller Class II), APC + CAF might not be the most suitable therapeutic choice.


Assuntos
Retração Gengival , Tecido Conjuntivo , Gengiva , Humanos , Retalhos Cirúrgicos , Raiz Dentária , Resultado do Tratamento
10.
Eur J Ophthalmol ; : 1120672120902034, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31983220

RESUMO

PURPOSE: To evaluate the changes of corneal biomechanics and the intraocular pressure during pregnancy in a Chinese healthy female population. METHODS: A total of 222 unrelated Chinese females were recruited: 52 non-pregnant, 15 pregnant in the first trimester, 68 pregnant in the second trimester, and 87 pregnant in the third trimester. The intraocular pressure and corneal biomechanical parameters, including corneal-compensated intraocular pressure, Goldmann-correlated intraocular pressure, corneal hysteresis, and corneal resistance factor, were measured by an Ocular Response Analyzer G3. Central corneal thickness was measured by Lenstar (LS900). RESULTS: Corneal hysteresis and corneal resistance factor were significantly higher in pregnant women at the second and third trimesters. Corneal-compensated intraocular pressure was lower in women at the third trimester of pregnancy (p = 0.023), but the difference became insignificant after adjustment for corneal hysteresis. Central corneal thickness was marginally higher in pregnant women than non-pregnant women (p = 0.032). There was a negative correlation between corneal-compensated intraocular pressure and corneal hysteresis (r = -0.337, p < 0.001) and a positive correlation between central corneal thickness and corneal hysteresis (r = 0.711, p < 0.0001). After adjustment for corneal-compensated intraocular pressure, corneal hysteresis remained significantly higher in the second and third trimesters of pregnant women than non-pregnant women (p = 0.031, p = 0.005). CONCLUSION: This study revealed a significant increase in corneal hysteresis and corneal resistance factor in the second and third trimesters. The increase of corneal hysteresis was independent of corneal-compensated intraocular pressure, indicating pregnant females have unique characteristics in corneal-compensated intraocular pressure and corneal biomechanical properties that may be related to glaucoma and corneal ectatic diseases in pregnancy.

11.
J Asthma ; : 1-8, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31922916

RESUMO

Objective: This study aimed to evaluate the diagnostic value of the modified hypertonic saline bronchial provocation test (HS-BPT) for children with asthma by using the high-power Aerosol Provocation System (APS).Methods: A total of 330 children suspected of having asthma and receiving HS-BPT-APS were included in this prospective survey conducted in Guangzhou, China from February 2017 to September 2018. The positive rate of HS-BPT-APS and the volume and types of adverse reactions were observed. There was also a retrospective cohort of 123 children with suspected asthma who underwent a methacholine BPT from 2015 to 2017. Using the method of nearest neighbor matching, a comparison was made of the positive rate and adverse reaction between the methacholine BPT group and HS-BPT-APS group.Results: The total positive rate of HS-BPT-APS was 43.9%. Common adverse reactions included cough, wheezing and chest tightness. There were no serious adverse reactions. Results of nearest neighbor matching showed a difference in the positive rate between the methacholine BPT group and HS-BPT-APS group (8.1% vs 18.2%, p = 0.026), but there was no statistically significant difference between the age groups in patients who received the methacholine BPT or HS-BPT-APS. There was a similar adverse reaction rate in the two groups (p = 0.609).Conclusions: HS-BPT-APS is simple, safe, and time-saving, with few adverse reactions. The positive rate of HS-BPT-APS was higher than that of methacholine BPT in children with asthma. HS-BPT-APS may be a valuable tool in the diagnosis of children with asthma, and further study is required.

12.
Hum Mutat ; 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31981384

RESUMO

Haploinsufficiency of ARID1B (AT-rich interaction domain 1B) has been involved in autism spectrum disorder, nonsyndromic and syndromic intellectual disability, and corpus callosum agenesis. Growth impairment is a major clinical feature caused by ARID1B mutations; however, the mechanistic link has not been elucidated. Here, we confirm that growth delay is a common characteristic of patients with ARID1B mutations, which may be associated with dysregulation of the Wnt/ß-catenin signaling pathway. An analysis of patients harboring pathogenic variants of ARID1B revealed that nearly half had short stature and nearly all had below-average height. Moreover, the percentage of patients with short stature increased with age. Knockdown of arid1b in zebrafish embryos markedly reduced body length and perturbed the expression of both chondrogenic and osteogenic genes including sox9a, col2a1a, runx2b, and col10a1. Knockout of Arid1b in chondrogenic ATDC5 cells inhibited chondrocyte proliferation and differentiation. Finally, Wnt/ß-catenin signaling was perturbed in Arid1b-depleted zebrafish embryos and Arid1b knockout ATDC5 cells. These data indicate that ARID1B modulates bone growth possibly via regulation of the Wnt/ß-catenin pathway, and may be an appropriate target for gene therapy in disorders of growth and development.

14.
Int J Lab Hematol ; 42(2): 206-213, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31958215

RESUMO

INTRODUCTION: To assess the clinical performance and correlations of automated chemiluminescence assay (CIA) and enzyme-linked immunosorbent assay (ELISA) for detecting antiphospholipid (aPL) antibodies in the diagnosis of antiphospholipid syndrome (APS). METHODS: The study recruited 505 subjects, including 192 with APS, 193 with connective tissue diseases other than APS, and 120 healthy donors. We measured anticardiolipin (aCL) and anti-ß2-glycoprotein I (anti-ß2GPI) antibodies IgG, IgM, and IgA in all the samples using both CIA and ELISA. RESULTS: Total agreement between the two methods ranged from 83.50% for anti-ß2GPI IgG antibodies to 92.76% for anti-ß2GPI IgM antibodies in all the groups. Anti-ß2GPI and aCL IgG assays showed the highest Spearman's rho coefficients (anti-ß2GPI IgG = 0.742, aCL IgG = 0.715). Anti-ß2GPI IgG CIA showed the highest sensitivity for diagnosis of APS at 80.21%, which was significantly higher than the sensitivity of anti-ß2GPI IgG ELISA (52.08%). For diagnosis of APS, anti-ß2GPI IgG CIA had the best discrimination power with the area under the curves (AUC) of 0.922, followed by aCL IgG CIA (AUC of 0.905). While the CIA AUC was slightly higher in all cases, the difference was not statistically significant. CONCLUSION: CIA measurements had a good agreement and correlation with comparative ELISA assays. The CIA anti-ß2GPI IgG however was significantly more sensitive for APS diagnosis. The two assay methodologies showed comparable predictive powers and support the value of the CIA method for improved diagnosis and management of patients with APS.

15.
Prenat Diagn ; 40(3): 324-332, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31697851

RESUMO

OBJECTIVE: This study aimed to validate the feasibility of haplotype-based noninvasive prenatal diagnosis (NIPD) of cobalamin C (cblC) deficiency. METHOD: This method includes three steps: First, targeted sequencing was performed on 21 families affected by cblC deficiency (including the couples and probands). Second, parental haplotypes linked with the pathogenic variant were determined using the genotypes of trios. Then, the fetal haplotypes were inferred through a parental haplotype assisted hidden Markov model (HMM). The NIPD results were confirmed by using the invasive procedures. RESULTS: Twenty-one fetal genotypes were successfully inferred by NIPD including three compound heterozygotes with cblC deficiency, nine heterozygote carriers of cblC deficiency, and nine normal fetuses. The NIPD results were confirmed using the invasive procedures with 100% concordant rate. CONCLUSION: This result has shown that haplotype-based NIPD of cblC deficiency has high concordant rate and indicated potential clinical utility as a pregnancy diagnosis method for high-risk carrier couples.

16.
Int J Oncol ; 56(1): 139-150, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31789389

RESUMO

Unc­5 Netrin Receptor C (UNC5C) is a netrin­1 dependence receptor that mediates the induction of apoptosis in the absence of netrin­1. The present study found that UNC5C is heterogeneously expressed in breast cancer cell lines. By knocking down UNC5C in SK­BR­3 and ZR­75­30 cells and overexpressing UNC5c in MDA­MB­231 cells, it was demonstrated that UNC5C exerts an inhibitory effect on the growth and metastasis of breast cancer cells. The mechanism involved a UNC5C­knockdown­induced enhancement of matrix metalloproteinase (MMP)3, MMP7, MMP9 and MMP10 expression via activation of the PI3K/AKT, ERK and p38 MAPK signaling pathways. Notably, UNC5C directly interacted with integrin α6, which is involved in the growth and metastasis of breast cancer cells. Additionally, UNC5C­knockdown enhanced the phosphorylation of FAK and SRC, which are key kinases in the netrin­1/Unc5C and netrin­1/integrin α6/ß4 signaling pathways. This suggests that netrin­1 functions as an integrator for both the netrin­1/Unc5C and netrin­1/integrin α6/ß4 signaling pathways. UNC5C­knockdown potentiated netrin­1/integrin α6/ß4 signaling. Given that UNC5C­knockdown inhibited integrin­liked protein kinase phosphorylation at Thr­173, at least in SK­BR­3 cells, this may be an inhibitory phosphorylation site rather than activating phosphorylation site for relaying integrin signaling.

17.
IEEE Trans Pattern Anal Mach Intell ; 42(1): 126-139, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30296212

RESUMO

With the popularity of mobile sensor technology, smart wearable devices open a unprecedented opportunity to solve the challenging human activity recognition (HAR) problem by learning expressive representations from the multi-dimensional daily sensor signals. This inspires us to develop a new algorithm applicable to both camera-based and wearable sensor-based HAR systems. Although competitive classification accuracy has been reported, existing methods often face the challenge of distinguishing visually similar activities composed of activity patterns in different temporal orders. In this paper, we propose a novel probabilistic algorithm to compactly encode temporal orders of activity patterns for HAR. Specifically, the algorithm learns an optimal set of latent patterns such that their temporal structures really matter in recognizing different human activities. Then, a novel probabilistic First-Take-All (pFTA) approach is introduced to generate compact features from the orders of these latent patterns to encode the entire sequence, and the temporal structural similarity between different sequences can be efficiently measured by the Hamming distance between compact features. Experiments on three public HAR datasets show the proposed pFTA approach can achieve competitive performance in terms of accuracy as well as efficiency.

18.
Ann Transl Med ; 7(20): 586, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31807567

RESUMO

Background: Acute variceal bleeding is one of the critical complications in patients with liver cirrhosis. Severe renal vasoconstriction in consequence of low peripheral vascular resistance triggers the reduction of glomerular filtration rate (GFR), and thus induces acute kidney injury (AKI)/hepato-renal syndrome (HRS). Terlipressin and octreotide have been used in the management of cirrhotic patients with variceal bleeding. Also, terlipressin has been recommended as the international first-line pharmacological therapy for the treatment of HRS. In addition, the use of renal functional magnetic resonance imaging (fMRI) has become increasingly prevalent in research and clinical applications. However, the renal function-protective effect of terlipressin and octreotide and the value of fMRI in monitoring renal function remains unclear in patients with cirrhosis undergoing acute variceal bleeding. Methods: This is a multicenter, randomized controlled trial (RCT). Participants will be 1:1 assigned randomly into either terlipressin or octreotide groups. Sixty participants with clinically and/or pathologically diagnosed cirrhosis and active gastroesophageal variceal bleeding (GVB) will be recruited in several sites in China. Participants will receive either the treatment of terlipressin or octreotide after assigned into each group. The primary end point for the trial is the renal function. The secondary end points are (I) renal perfusion; (II) renal blood oxygenation; (III) failure to control bleeding; (IV) intra-hospital rebleeding; (V) intra-hospital mortality; (VI) adverse events (AE); (VII) overall survival. Statistical analysis including multivariate Cox regression, Kaplan-Meier analysis with log-rank test, etc. will be conducted. Discussion: The study will provide new insight into the protection of renal function in the process of the treatment of variceal bleeding in patients with cirrhosis. Trial registration number: NCT04028323.

19.
Front Oncol ; 9: 1251, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31824844

RESUMO

Quiescent caner stem cells are identified as a subpopulation of colon cancer cells in dormant state and possess strong stem-cell like characteristics. Previously, we have identified this subpopulation in colorectal cancer (quiescent colon cancer stem cells, QCCSCs), and find QCCSCs are sensitive to the apoptotic effect of IFN-γ, which is attributed to their high IFN-γR expression levels. Microarray and bioinformatic analysis indicate miR-4666-3p is low expressed in QCCSCs and target IFN-γR1/2, which is proved by luciferase assay and western-blot. Furthermore, we find miR-4666-3p could also target TGF-ßR1 to block the activation of TGF-ß1/Smad pathway, therefore function as a tumor suppressor gene to inhibit the stemness of colon cancer cells. Besides, compared with QCCSCs, we find the TGF-ß1 expression also decreased with the weakening of stemness properties. In terms of mechanism, our result reveal TGF-ß1 is the target gene of miR-329, which is also high expressed in non-QCCSCs. Thereafter, we perform gain- and loss- function experiments to confirm the synergistic effect between miR-4666-3p and miR-329 in blocking the activation of TGF-ß/Smad pathway. Finally, we evaluate the expression of both miR-4666-3p and miR-329 in 73 tumor specimens and paired normal tissue, and find both two miRNAs are related to unfavorable prognosis and advanced tumor stage in colorectal cancer. Our study revealed a novel epigenetic regulation mechanism in colon cancer stem cells, which could be exploited as a novel therapeutic strategy for cancer treatment.

20.
Dis Markers ; 2019: 2046825, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31814857

RESUMO

Background and Aim: Aspartate aminotransferase-to-platelet ratio index (APRI) is widely used in the assessment of fibrosis and cirrhosis, especially in patients with chronic hepatitis. However, the prognostic value of APRI in patients with chronic hepatitis with regard to the prediction of hepatocellular carcinoma (HCC) occurrence remains controversial. The objective of this meta-analysis is to investigate the association between APRI and HCC risk on the basis of cohort studies. Methods: We systematically reviewed PubMed, EMBASE, Web of Science, and Chinese National Knowledge Infrastructure databases for relevant cohort studies up to May 1, 2019. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for total and subgroup analyses were calculated with Stata 12.0 software for the assessment of the relationship between APRI and HCC risk. Results: A total of 13 studies, involving 8897 patients, were included in the meta-analysis, of which 11 explored the association between pretreatment APRI and HCC risk and four reported the relationship between posttreatment APRI and HCC risk. Pooled results showed that an elevated level of pretreatment APRI was associated with increased HCC risk (HR = 2.56, 95% CI: 1.78-3.68). When stratified by hepatitis type, high pretreatment APRI predicted HCC development in patients with chronic hepatitis B (CHB) and C (CHC) but not in alcoholic liver cirrhosis (ALC). In the subgroup analyses of study region, cut-off value, sample size, and analysis method, the relationship between high pretreatment APRI and increased HCC risk was significant. Meanwhile, patients with a high level of posttreatment APRI suffered from high HCC risk (HR = 3.69, 95% CI: 2.52-5.42). Conclusion: Results revealed a significant association between elevated APRI and HCC development in patients with chronic hepatitis, suggesting that APRI might serve as a valuable predictor for HCC risk in patients with chronic hepatitis.

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