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1.
J Nanosci Nanotechnol ; 20(4): 2508-2513, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492269

RESUMO

Nanofluidics devices with two-dimensional nano-structures have attracted extensive interests for biological and chemical applications. The fabrication of nanoscale mask patterns with controllable line width is an indispensable process for manufacturing two-dimensional nano-structures. However, a simple and low-cost method for fabricating two-dimensional nano-patterns is still a challenge. In this work, a novel simple and low-cost method for fabricating nanoscale mask patterns with controllable line width, based on the ultraviolet exposure is presented. In the experiment, a layer of AZ5214 reversal photoresist was exposed to the ultraviolet light through the photomask with microscale patterns. After the lithography, nanoscale photoresist mesas patterns instead of microscale patterns were produced. The photoresist mesas with 400~800 nm width were fabricated. Meanwhile, by adjusting the parameters of exposure time, various nanoscale dimensions of photoresist mesas can be obtained. The proposed method overcomes limitations of the conventional ultraviolet lithography technology without the need to the expensive nanolithography equipment. Our novel fabrication method should be a useful tool for two-dimensional nano-structures fabrication due to its advantages of simple fabrication process, well controllability, and low-cost.

2.
BMC Cancer ; 19(1): 871, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477094

RESUMO

BACKGROUND: The relationship between first-degree family history of female breast cancer and prostate cancer risk in the general population remains unclear. We performed a meta-analysis to determine the association between first-degree family history of female breast cancer and prostate cancer risk. METHODS: Databases, including MEDLINE, Embase, and Web of Science, were searched for all associated studies that evaluated associations between first-degree family history of female breast cancer and prostate cancer risk up to December 31, 2018. Information on study characteristics and outcomes were extracted based on the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. The quality of evidence was assessed using the GRADE approach. RESULTS: Eighteen studies involving 17,004,892 individuals were included in the meta-analysis. Compared with no family history of female breast cancer, history of female breast cancer in first-degree relatives was associated with an increased risk of prostate cancer [relative risk (RR) 1.18, 95% confidence interval (CI) 1.12-1.25] with moderate-quality evidence. A history of breast cancer in mothers only (RR 1.19, 95% CI 1.10-1.28) and sisters only (RR 1.71, 95% CI 1.43-2.04) was associated with increased prostate cancer risk with moderate-quality evidence. However, a family history of breast cancer in daughters only was not associated with prostate cancer incidence (RR 1.74, 95% CI 0.74-4.12) with moderate-quality evidence. A family history of female breast cancer in first-degree relatives was associated with an 18% increased risk of lethal prostate cancer (95% CI 1.04-1.34) with low-quality evidence. CONCLUSIONS: This review demonstrates that men with a family history of female breast cancer in first-degree relatives had an increased risk of prostate cancer, including risk of lethal prostate cancer. These findings may guide screening, earlier detection, and treatment of men with a family history of female breast cancer in first-degree relatives.

3.
Int Urol Nephrol ; 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31494858

RESUMO

BACKGROUND: The continuous intake of antithrombotic drugs during holmium laser enucleation of the prostate (HoLEP) remains nonconsensual. We aim to pool those controversial evidence and provide practical guidance of oral antithrombotics on HoLEP for benign prostate hyperplasia (BPH). METHOD: PubMed, Embase and CENTRAL database were systematically searched up to June 2019 for trials on patients with and without oral antithrombotics undergoing HoLEP. Number of events and mean value with standard deviation were, respectively, extracted for dichotomous and continuous parameters. Subgroup analyses of anticoagulation and antiplatelet were also performed. All statistical analyses were conducted with Review Manager v.5.3 software. Newcastle-Ottawa Scale (NOS) was used to assess the quality of selected trials. RESULT: Nine studies with 5528 patients were eventually selected, and patients included were generally older than 65 years. It revealed that the non-antithrombotic group had a lower rate of blood transfusion (OR 0.21, 95% CI 0.10-0.45, P < 0.0001), bladder tamponade (OR 0.30, 95% CI 0.13-0.69, P = 0.004) and acute urine retention (OR 0.52, 95% CI 0.30-0.89, P = 0.02). Operation time was also shorter (MD - 10.31, 95% CI - 12.76 to - 7.85, P < 0.00001) in the non-antithrombotic group, but the heterogeneity was considerable (I2 = 75%). Subgroup analyses were generally consistent with the primary analysis except the non-anticoagulation and anticoagulation group having similar operation time (MD 6.66, 95% CI - 7.15 to 20.48, P = 0.34). CONCLUSION: The current study confirmed that continuous intake of antithrombotic drugs could significantly increase the risk of bleeding and blood transfusion, bladder tamponade and acute urine retention.

4.
Small ; : e1903831, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31513340

RESUMO

In this study, a highly sensitive and self-driven near-infrared (NIR) light photodetector based on PdSe2 /pyramid Si heterojunction arrays, which are fabricated through simple selenization of predeposited Pd nanofilm on black Si, is demonstrated. The as-fabricated hybrid device exhibits excellent photoresponse performance in terms of a large on/off ratio of 1.6 × 105 , a responsivity of 456 mA W-1 , and a high specific detectivity of up to 9.97 × 1013 Jones under 980 nm illumination at zero bias. Such a relatively high sensitivity can be ascribed to the light trapping effect of the pyramid microstructure, which is confirmed by numerical modeling based on finite-difference time domain. On the other hand, thanks to the broad optical absorption properties of PdSe2 , the as-fabricated device also exhibits obvious sensitivity to other NIR illuminations with wavelengths of 1300, 1550, and 1650 nm, which is beyond the photoresponse range of Si-based devices. It is also found that the PdSe2 /pyramid Si heterojunction device can also function as an NIR light sensor, which can readily record both "tree" and "house" images produced by 980 and 1300 nm illumination, respectively.

5.
Mol Med ; 25(1): 35, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31370803

RESUMO

OBJECTIVES: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease whose onset and progression are affected by genetic and environmental factors. The purpose of this study is to identify the influence of gut microbiota in the pathogenesis of SLE, and to investigate the mechanism involved. METHODS: Fecal microbiota from C57/BL6 mice and SLE prone mice were examined using next-generation sequencing (NGS). Germ free mice were given fecal microbiota transplantation (FMT), and their gut microbiome and gene expression in recipients' colons were examined by NGS. The anti-double stranded DNA (anti-dsDNA) antibodies in recipients were determined using an enzyme-linked immunosorbent assay (ELISA). The immune cell profiles of mice were analyzed by flow cytometry at the 3rd week after FMT, and the expression of genes associated with SLE after FMT was determined using quantitative real-time PCR (qRT-PCR). RESULTS: The fecal microbiota of SLE mice had lower community richness and diversity than healthy mice. Fecal microbiota of recipient mice were similar to their donors. Fecal microbiome from SLE mice could lead to a significant increase of anti-dsDNA antibodies and promote the immune response in recipient mice. Our results also indicated that fecal microbiome from SLE mice resulted in significant changes in the distribution of immune cells and upregulated expression of certain lupus susceptibility genes. CONCLUSIONS: SLE is associated with alterations of gut microbiota. Fecal microbiome from SLE mice can induce the production of anti-dsDNA antibodies in germ free mice and stimulate the inflammatory response, and alter the expression of SLE susceptibility genes in these mice.

6.
Int J Neural Syst ; 29(7): 1950005, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31387489

RESUMO

Although electroconvulsive therapy (ECT) is one of the most effective treatments for major depressive disorder (MDD), the mechanism underlying the therapeutic efficacy and side effects of ECT remains poorly understood. Here, we investigated alterations in the cortical morphological measurements including cortical thickness (CT), surface area (SA), and local gyrification index (LGI) in 23 MDD patients before and after ECT. Furthermore, multivariate pattern analysis using linear support vector machine (SVM) was applied to investigate whether the changed morphological measurements can be effective indicators for therapeutic efficacy of ECT. Surface-based morphometry (SBM) analysis found significantly increased vertex-wise and regional cortical thickness (CT) and surface area (SA) in widespread regions, mainly located in the left insula (INS) and left fusiform gyrus, as well as hypergyrification in the left middle temporal gyrus (MTG) in MDD patients after ECT. Partial correlational analyses identified associations between the morphological properties and depressive symptom scores and impaired memory scores. Moreover, SVM result showed that the changed morphological measurements were effective to classify the MDD patients before and after ECT. Our findings suggested that ECT may enhance cortical neuroplasticity to facilitate neurogenesis to remit depressive symptoms and to impair delayed memory. These findings indicated that the cortical morphometry is a good index for therapeutic efficacy of ECT.

7.
Medicine (Baltimore) ; 98(35): e17060, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464967

RESUMO

BACKGROUND: To evaluate the effectiveness and safety of neoadjuvant chemotherapy (NAC) for locally advance prostate patients undergoing radical prostatectomy. METHODS: PubMed/Medline, EMBASE, Web of Science, Ovid, Web of Knowledge, and Cochrane Library will be searched for studies related to the topic. The identification, inclusion and exclusion flow charts will be conducted according to PRISMA guidelines. The identified reports will be critically appraised using GRADE approach. Bias and heterogeneity of included studies will be assessed, and outcome measurements from individual studies will be combined with 95% confidence interval using a fixed- or random-effects model if qualified. RESULTS: This study will provide evidence and data on the tolerance and efficacy of NAC followed by radical prostatectomy (RP). CONCLUSION: The application of taxanes-based chemotherapy has been widened to metastatic hormone sensitive prostate cancer in recent years. To be more vigorous, whether neoadjuvant administration of these cytotoxic agents can improve the outcome of RP in locally advance prostate cancer patients has been explored. This study aims to synthesis data regarding the adverse effect, response rate, recurrence, and survival from multiple trials, and to guide the healthcare practitioners using an evidence-based approach.

8.
Virus Res ; 272: 197728, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31442468

RESUMO

Egg-drop syndrome virus (EDSV) is an avian adenovirus that causes markedly decrease in egg production and in the quality of the eggs when it infects chickens. In this report, we engineered truncated fiber protein containing the entire knob domain and part of the shaft region as a vaccine candidate. The protein was obtained in the soluble fraction in Escherichia coli (E. coli), and expression level after nickel-affinity purification was 126 mg/L. By means of multiple characterization methods, it is demonstrated that the recombinant protein retains the native trimeric structure. A single inoculation with the structure-stabilized recombinant protein, even at the lowest dose of 2 µg, stimulated hemagglutination inhibition (HI) antibody responses in chickens, for at least 16 weeks. Neutralizing titers in sera from the protein immunized groups was similar to that of inactivated vaccine immunized group. The lymphocyte proliferation response and cytokine secretion were also induced in immunized SPF chickens. In addition, immunization with the fiber protein also significantly reduced the viral load in the liver. Taken together, these results suggest the truncated fiber protein as an effective single dose, long lasting and rapidly effective vaccine to protect against EDSV.

9.
Orthop Surg ; 11(4): 545-551, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31456323

RESUMO

OBJECTIVE: To assess the efficacy of tranexamic acid (TXA) in reducing total blood loss and transfusion, and the risk of thromboembolic events in patients undergoing periacetabular osteotomy (PAO) and high tibial osteotomy (HTO). METHODS: A systematic literature search was performed using PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), Embase (Ovid), Medline (Ovid), and Web of Science. ClinicalTrials.gov, American Academy of Orthopaedic Surgeons (AAOS), and Orthopaedic Trauma Association (OTA) conference proceedings were also searched to gain more eligible studies. The primary outcome measure was total blood loss and the blood transfusion rate of the TXA group versus control. The meta-analysis was conducted using the RevMan 5.3 and Stata 14.0 software. RESULTS: A total of six studies were included involving 665 patients. Three studies were PAO, and the other three were HTO. The total blood loss in PAO (WMD, -330.49; 95% CI, -390.16 to -270.83; P < 0.001) and HTO (WMD, -252.50; 95% CI, -356.81 to -148.18; P < 0.001) and hemoglobin decline (WMD, -0.74; 95% CI, -1.09 to -0.38; P < 0.001) were significantly less in the TXA group than in the control group. TXA could reduce transfusion rates in PAO (RR, 0.26; 95% CI, 0.09 to 0.75; P = 0.01) but had no effect on HTO (RR, 0.20; 95% CI, 0.01 to 4.10; P = 0.30). The wound complications (RR, 0.62; 95% CI, 0.13 to 2.94; P = 0.54) had no significant difference between TXA and control groups. CONCLUSIONS: This meta-analysis demonstrated that TXA reduces total blood loss and hemoglobin decline in patients undergoing PAO and is safe, but it has little benefit in regard to reducing transfusion rates or wound complications in HTO, so TXA might be unwarranted for routine use for HTO.

10.
Medicine (Baltimore) ; 98(31): e16543, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374016

RESUMO

BACKGROUND: Number of studies have been performed to investigate the relationship between the CYP1A1 rs4646903 polymorphism and male infertility risk, but the sample size was small and the results were conflicting. A meta-analysis was performed to assess these associations. METHODS: A systematic search was conducted to identify all relevant studies from Medline, Web of science, Embase, China biology medical literature database (CBM), China National Knowledge Infrastructure (CNKI), WanFang and Weipu (VIP) databases up to June 30, 2018. The odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of associations. All of the statistical analyses were conducted using Revman 5.3 and Stata 14.0. RESULTS: Ten studies involved 3028 cases and 3258 controls. Overall, significant association was observed between the CYP1A1 rs4646903 polymorphism and male infertility (C vs T: OR = 1.42, 95%CI = 1.14-1.76; CC vs TT: OR = 2.13, 95%CI = 1.36-3.34; CC vs CT+TT: OR = 1.96, 95%CI = 1.30-2.95; CC+CT vs TT: OR = 1.51, 95%CI = 1.16-1.97). In subgroup analysis by ethnic group, a statistically significant association was observed in Asians (C vs T: OR = 1.59, 95%CI = 1.22-2.08), but not in Non-Asians (C vs T: OR = 1.01, 95%CI = 0.79-1.30). Additionally, none of the individual studies significantly affected the association between CYP1A1 rs4646903 polymorphism and male infertility, according to sensitivity analysis. CONCLUSION: Our meta-analysis supports that the CYP1A1 rs4646903 polymorphism might contribute to individual susceptibility to male infertility in Asians.


Assuntos
Citocromo P-450 CYP1A1/genética , Infertilidade Masculina/etiologia , Infertilidade Masculina/genética , Predisposição Genética para Doença , Humanos , Masculino , Razão de Chances
11.
J Colloid Interface Sci ; 555: 315-322, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31394318

RESUMO

Catalysis benefits from biomimetic materials with sophisticated structures because a variety of functions can be integrated into one structure, satisfying the demands of a diverse range of applications. Magnetic catalysts have been widely used in various applications, but the magnetic components are most commonly used for recycling. In this study, we report the fabrication of magnetic nanocatalysts composed of a support of magnetic nanobars and Ag nanoparticles confined between two silica layers. Notably, the catalysts are constructed as nanoscale stirring bars that are able to generate disturbances at this scale. More importantly, the catalysts can be applied in both macro- and micro-systems, effectively addressing the conventional mixing method. The catalysts can then be conveniently separated from the system after use. The performances of magnetic nanoscale catalysts are well maintained through recycling.

12.
Environ Sci Technol ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31455077

RESUMO

Wind energy is key to addressing the global climate challenge, but its development is subject to potential constraint of finite primary materials. Prior studies on material demand forecasting of wind power development are often limited to a few materials and with low technological resolution, thus hindering a comprehensive understanding of the impact of micro-engineering parameters on the resource implications of wind energy. In this study, we developed a component-by-component and stock-driven prospective material flow analysis model, and used bottom-up data on engineering parameters and wind power capacities to characterize the materials demand and secondary supply potentials of wind energy development in Denmark, a pioneering and leading country in wind power. We also explicitly addressed the uncertainties in the prospective modeling by the means of statistical estimation and sensitivity analysis methods. Our results reveal increasing challenges of materials provision and end-of-life (EoL) management in Denmark's ambitious transition towards 100% renewable energy in the next decades. Harnessing potential secondary resource supply from EoL and extending lifetime could curtail the primary material demand, but they could not fully alleviate the material supply risk. Such model framework that considers bottom-up engineering parameters with increased precision could be applied to other emerging technologies and help reveal synergies and trade-offs of relevant resource, energy, and climate strategies in the future renewable energy and climate transition.

13.
Int J Biol Macromol ; 139: 587-595, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31381914

RESUMO

Egg drop syndrome virus (EDSV) is an avian adenovirus that causes markedly decrease in egg production, and in the quality of the eggs when it infects chickens. Until now, EDSV virus-cell interactions are poorly understood, and the cellular receptor is still unknown. In the present study, we determined the atomic structure of the fiber head of EDSV (residues 377-644) at 2.74 Šresolution. Structure comparison with the (chick embryo lethal orphan) CELO long fiber head and human adenovirus fiber heads reveals that the avian adenovirus may interact with the same attachment factor in a unique fashion. Based on the previous studies of CELO virus, we assumed that the chicken coxsackievirus and adenovirus receptor (CAR) may be the attachment factor. We then demonstrate that the chicken CAR serves as a cellular attachment factor for EDSV based on three lines of evidences. Taken together, the results presented here are helpful for further exploring the pathogenesis related to the interaction between EDSV and host cells, and may be used for vaccine development and intervention strategies against EDSV infection.

14.
J Med Chem ; 62(17): 7923-7940, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31381333

RESUMO

Aberrant activation of Bruton's tyrosine kinase (BTK) plays an important role in pathogenesis of B-cell lymphomas, suggesting that inhibition of BTK is useful in the treatment of hematological malignancies. The discovery of a more selective on-target covalent BTK inhibitor is of high value. Herein, we disclose the discovery and preclinical characterization of a potent, selective, and irreversible BTK inhibitor as our clinical candidate by using in vitro potency, selectivity, pharmacokinetics (PK), and in vivo pharmacodynamic for prioritizing compounds. Compound BGB-3111 (31a, Zanubrutinib) demonstrates (i) potent activity against BTK and excellent selectivity over other TEC, EGFR and Src family kinases, (ii) desirable ADME, excellent in vivo pharmacodynamic in mice and efficacy in OCI-LY10 xenograft models.

15.
Medicine (Baltimore) ; 98(34): e16923, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441877

RESUMO

RATIONALE: There are already several reports concerning the occurrence of urethral diverticulum (UD) in female patients, but only rarely has a article describing UD combined with UD calculi or squamous carcinoma been published. Moreover, a case with squamous carcinoma and UD calculi at the same time has never been reported, making this the first case report about this condition. PATIENT CONCERNS: A 43-year-old woman presented to the gynaecology department with a complaint of a hard mass beneath the anterior vaginal wall. DIAGNOSES: Transvaginal ultrasound (TVU) revealed a UD. INTERVENTIONS: We performed a standard urethral diverticular excision. Intraoperatively, we identified and removed a stone from the diverticulum. The intraoperative finding of a stone challenged the diagnosis of UD, with subsequent histological examination of biopsy tissue from the mass demonstrating broadly squamous metaplasia. OUTCOMES: The broadly squamous metaplasia predominantly originated from the stone, and the stone was entirely removed. No complications occurred during the whole follow-up period. Moreover, after the 12-month follow-up, there was no diverticular recurrence or carcinoma metastasis. LESSONS: UD calculi may be considered a risk factor for female urethra squamous metaplasia, which with the potential of squamous carcinoma, so patients will be advised to treat this condition immediately.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Neoplasias Uretrais/diagnóstico , Adulto , Biópsia , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Divertículo/complicações , Divertículo/diagnóstico por imagem , Divertículo/cirurgia , Feminino , Humanos , Imagem por Ressonância Magnética , Metaplasia , Neoplasias Uretrais/complicações , Neoplasias Uretrais/patologia , Neoplasias Uretrais/cirurgia , Cálculos Urinários/complicações , Cálculos Urinários/diagnóstico por imagem , Cálculos Urinários/cirurgia
16.
Drug Des Devel Ther ; 13: 2503-2512, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31440033

RESUMO

Background: Osteoarthritis (OA) is a common joint disease, which is characterized by degradation of articular cartilage. Evidence indicated that miR-23b-3p was upregulated in cartilage tissues of a patient with OA. However, the mechanism by which miR-23b-3p regulates the occurrence and development of OA remains unclear. Thus, this study aimed to investigate the role of miR-23b-3p in the progression of OA. Methods: In this study, qRT-PCR was used to measure the expression of miR-23b-3p in OA tissue samples and normal controls, respectively. Western blotting assay was performed to detect the levels of collagen II, aggrecan, Bax and active caspase 3 in CHON-001 cells. In addition, the dual-luciferase reporter system assay was used to detect the interaction between miR-23b-3p and COL11A2 in OA. Results: The levels of miR-23b-3p were upregulated, while the expressions of collagen II and aggrecan were decreased in OA tissues and in IL-1ß-treated CHON-001 cells. In addition, IL-1ß significantly induced apoptosis of CHON-001 cells via increasing the levels of Bax and active caspase 3. However, downregulation of miR-23b-3p markedly inhibited IL-1ß-induced apoptosis in CHON-001 cells via increasing the collagen II and aggrecan levels and decreasing Bax and active caspase 3 expressions. Meanwhile, dual-luciferase assay showed that COL11A2 was the direct target of miR-23b-3p in CHON-001 cells. Overexpression of miR-23b-3p markedly decreased the level of COL11A2 in cells. Moreover, downregulation of miR-23b-3p alleviated synovitis/cartilage destruction and reduced Osteoarthritis Research Society International scores and subchondral bone thickness in vivo. Conclusion: Downregulation of miR-23b-3p could alleviate the progression of OA through upregulating COL11A2 in vivo and in vitro. Therefore, downregulation of miR-23b-3p might be a potential therapeutic strategy for the treatment of OA.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31272350

RESUMO

AIM AND OBJECTIVE: Flap endonuclease-1 (FEN1) plays a central role in DNA replication and DNA damage repair process. In mammal, FEN1 functional sites variation is related to cancer and chronic inflammation, and supports the role of FEN1 as a tumor suppressor. However, FEN1 is overexpressed in multiple types of cancer cells and is associated with drug resistance, supporting its role as an oncogene. Hence, it is vital to explore the multi-functions of FEN1 in normal cell metabolic process. This study was undertaken to examine how the gene expression profile changes when FEN1 is down regulated in 293T cells. MATERIALS AND METHODS: Using the RNA sequencing and real-time PCR approaches, the transcript expression profile of FEN1 knockdown HEK293T cells have been detected for the next step evaluation, analyzation, and validation. RESULTS: Our results confirmed that FEN1 is important for cell viability. We showed that when FEN1 down regulation led to interruption of nucleic acids related metabolisms and cell cycle related metabolisms are significantly interrupted. FEN1 may also participate in non-coding RNA processing, ribosome RNA processing, transfer RNA processing, ribosome biogenesis, virus infection and cell morphogenesis. CONCLUSION: These findings provide insight into how FEN1 nuclease might regulate a wide variety of biological processes, and laid the foundation for understanding the role other RAD2 family nucleases in cell growth and metabolism.

18.
Gut ; 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31300513

RESUMO

OBJECTIVE: SETD2, the sole histone H3K36 trimethyltransferase, is frequently mutated or deleted in human cancer, including pancreatic ductal adenocarcinoma (PDAC). However, whether SETD2/H3K36me3 alteration results in PDAC remains largely unknown. DESIGN: TCGA(PAAD) public database and PDAC tissue array with SETD2/H3K36me3 staining were used to investigate the clinical relevance of SETD2 in PDAC. Furthermore, to define the role of SETD2 in the carcinogenesis of PDAC, we crossed conditional Setd2 knockout mice (Pdx cre Setd2 flox/flox) together with Kras G12D mice. Moreover, to examine the role of SETD2 after ductal metaplasia, Crisp/cas9 was used to deplete Setd2 in PDAC cells. RNA-seq and H3K36me3 ChIP-seq were performed to uncover the mechanism. RESULTS: SETD2 mutant/low expression was correlated with poor prognosis in patients with PDAC. Next, we found that Setd2 acted as a putative tumour suppressor in Kras-driven pancreatic carcinogenesis. Mechanistically, Setd2 loss in acinar cells facilitated Kras-induced acinar-to-ductal reprogramming, mainly through epigenetic dysregulation of Fbxw7. Moreover, Setd2 ablation in pancreatic cancer cells enhanced epithelia-mesenchymal transition (EMT) through impaired epigenetic regulation of Ctnna1. In addition, Setd2 deficiency led to sustained Akt activation via inherent extracellular matrix (ECM) production, which would favour their metastasis. CONCLUSION: Together, our findings highlight the function of SETD2 during pancreatic carcinogenesis, which would advance our understanding of epigenetic dysregulation in PDAC. Moreover, it may also pave the way for development of targeted, patients-tailored therapies for PDAC patients with SETD2 deficiency.

19.
Medicine (Baltimore) ; 98(26): e16122, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261530

RESUMO

BACKGROUND: The aim of this study was to assess the sensitivity and accuracy of magnetic resonance imaging-guided targeted biopsy (MRI-TB) in patients undergoing active surveillance (AS) procedure. METHODS: We searched databases to identify relevant studies which compared MRI-TB with systemic biopsy for diagnosing prostate cancer in patients on AS. Outcomes included sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), area under the curve (AUC) and publication bias of AS group, confirmatory biopsy group and follow-up biopsy group. RESULTS: Fourteen articles involving 1693 patients were included. In AS group, the sensitivity was 0.62 (95% confidence interval [CI], 0.57-0.68), specificity was 0.89 (95% CI, 0.87-0.90), NLR was 0.43 (0.31-0.60), PLR was 4.90 (3.50-6.86), DOR was 12.75 (7.22-22.51), and AUC was 0.8645. In confirmatory biopsy group, the sensitivity was 0.67 (0.59-0.74), specificity was 0.89 (0.86-0.91), NLR was 0.42 (0.27-0.65), PLR was 4.94 (3.88-6.30), DOR was 14.54 (9.60-22.02), and AUC was 0.8812. In follow-up biopsy group, the sensitivity was 0.35 (0.22-0.51), specificity was 0.88 (0.82-0.92), NLR was 0.76 (0.52-1.11), PLR was 3.06 (1.71-5.50), DOR was 4.41 (2.15-9.03), and AUC was 0.8367. CONCLUSION: MRI-TB has a moderate-to-high diagnostic accuracy for diagnosing and reclassifying patients on AS with high specificity and AUC value under the SROC curve.


Assuntos
Biópsia Guiada por Imagem , Imagem por Ressonância Magnética Intervencionista , Neoplasias da Próstata/classificação , Neoplasias da Próstata/diagnóstico , Humanos , Masculino , Neoplasias da Próstata/patologia , Medição de Risco
20.
Medicine (Baltimore) ; 98(26): e16166, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261546

RESUMO

RATIONALE: The placenta membranacea (PM) is a rare type of placental abnormality, which is associated with placenta previa, antepartum hemorrhage (APH), postpartum hemorrhage (PPH), chorioamnionitis, fetal growth restriction (FGR), preterm birth even stillbirth. The purpose of this case report is to summarize the characteristics and analyze the relevant factors of PM. PATIENTS CONCERNS: Repetitive B-ultrasound of the first patient demonstrated a thin placenta covering the most part of uterine wall, which completely covers the internal cervical ostium for 22 weeks. B-ultrasound of the second patient showed placenta partially covering the internal cervical ostium and fetus small for gestation age for 23 days. The third patient complained of abdominal pain and vaginal discharge for 1 day. DIAGNOSES: Diagnosis of PM is based on Doppler ultrasound apparatus, and confirmed by pathology. INTERVENTIONS AND OUTCOMES: In the first patient, elective cesarean section was performed. The second patient required termination of pregnancy due to poor postnatal outcome. The third patient underwent intrauterine fetal death. Of these 3 cases, one delivered a term fetus by cesarean section complicated with placenta previa and placenta accreta, one terminated the pregnancy because of serious fetal growth retardation, and the other underwent intrauterine fetal death. LESSONS: High-resolution color Doppler ultrasound apparatus can improve the diagnostic accuracy, and close antenatal surveillance followed by proper arrangement of delivery may improve neonatal outcomes.


Assuntos
Placenta/anormalidades , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Placenta/diagnóstico por imagem , Placenta/patologia , Gravidez , Resultado da Gravidez , Ultrassonografia Doppler em Cores , Ultrassonografia Pré-Natal , Adulto Jovem
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