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1.
Cancer Lett ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32081805

RESUMO

Bromodomain-containing protein 4 (BRD4) overexpression in non-small cell lung cancer (NSCLC) promotes cancer progression. Here, we show that miR-4651 selectively targets and negatively regulates BRD4 in A549 and primary human NSCLC cells. RNA pull-down experiments confirmed that miR-4651 directly binds to BRD4 mRNA. Further, ectopic overexpression of miR-4651 in A549 cells and primary NSCLC cells decreased BRD4 3'-UTR luciferase reporter activity and its expression, whereas miR-4651 inhibition elevated both. Functional studies demonstrated that NSCLC cell growth, proliferation, and migration were suppressed with ectopic miR-4651 overexpression but enhanced with miR-4651 inhibition. BRD4 re-expression using a 3'-UTR mutant BRD4 reversed A549 cell inhibition induced by miR-4651 overexpression. Further, miR-4651 overexpression or inhibition failed to alter the functions of BRD4-KO A549 cells. In vivo, miR-4651-overexpressing A549 xenografts grew slowly than control A549 xenografts in severe combined immunodeficient mice. Finally, miR-4651 was downregulated in human NSCLC tissues, correlating with BRD4 elevation. Together, miR-4651 targets BRD4 to inhibit NSCLC cell growth in vitro and in vivo.

2.
Nanotechnology ; 31(19): 195601, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31899909

RESUMO

In this work, a dense γ-In2Se3 nanosheet array has been fabricated using the chemical vapor deposition method under atmospheric pressure. Compared with crystal silicon, the photodetector based on the γ-In2Se3/p-Si heterojunction exhibits a high responsivity (96.7 mA W-1) at the near-infrared region, a presentable current on/off ratio (∼1000) and excellent detectivity (2.03 × 1012 jones). Simultaneously, the obtained photodetector demonstrated a fast response speed (0.15 ms/0.5 ms) and a broadband sensitive wavelength from ultraviolet (340 nm) to near-infrared (1020 nm). The photoelectric experimental data of the device shows that its high performance is attributed to the high-light absorption capacity of the material, the rational energy band structures of γ-In2Se3 and p-Si, and the effective separation of photo-generated carriers caused by the formed type-II heterojunction. Our work provides the primary experimental basis for the photodetection application of the γ-In2Se3 nanostructure.

3.
Gene ; 729: 144225, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31830514

RESUMO

BACKGROUND: Recently, extensive researches have explored the potential biomarker roles of microRNA-210 (miR-210) in non-small cell lung cancer (NSCLC). Inconsistent results, however, have prevented its widespread use in diagnosis. In the present study, we aimed to clarify the biomarker roles of miR-210 in NSCLC through a comprehensive meta-analysis and an integrative bioinformatics analysis. METHODS: Relevant studies were searched from several literature databases and included for qualitative synthesis based on the bivariate random-effects meta-analysis model. At the same time, we combined several bioinformatics analysis methods for exploring the potential mechanism of miR-210 involved in NSCLC. RESULTS: Overall, miR-210 yieled the area under curve (AUC) of 0.80 (95%CI: 0.76-0.83) with sensitivity of 0.66 (0.59-0.73) and specificity of 0.79 (0.74-0.84) for being applied to discriminate NSCLC cases from normal individuals. Besides, the combination biomarkers based on miR-210 had a higher diagnostic value accuracy than individual miR-210, with the sensitivity of 0.76 (0.72-0.79), specificity of 0.88 (0.86-0.90) and AUC of 0.91 (0.88-0.93). Through bioinformatics analysis including gene ontology, pathway enrichment, protein-protein interaction networks construction and analysis, crucial genes, pathways, modules and functional terms were identified, which were proved highly involved in the initiation and development of NSCLC. CONCLUSIONS: In summary, the current study suggests that miR-210 may function as a potential biomarker in NSCLC detection. Particularly, combination biomarkers may be more comprehensive indicators than single miR-210. However, the clinical diagnostic utilization and additional exploration still remain to be further tested and verified through more future studies.

4.
J Hazard Mater ; 381: 121006, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31442686

RESUMO

Here, a novel CuBi2O4/Bi2MoO6 (CBO/BMO) p-n heterojunction was fabricated and exhibited markedly improved photocatalytic inactivation capacity of E. coli cells under visible light excitation (λ > 420 nm) compared with pure CuBi2O4 and Bi2MoO6. The CBO/BMO-0.5 hybrid displayed the highest photoinactivation ability which could completely inactivate the E. coli cellswithin 4 h. The mechanism of photocatalytic disinfection towards E. coli of CBO/BMO heterojunctions was attributed to the disruption of cell-membrane, leakage and damage of cellular content including total protein and DNA as verified with SEM, fluorescence-base dead/live stain, sodium dodecyl sulfate polyacrylamide gel electropheresis (SDS-PAGE) and agarose gel electrophoresis (AGE). Additionally, the scavenge experiments showed that the reactive species h+, e- and •O2-play the predominant role in the photocatalytic system of CBO/BMO hybrids. The improved photocatalytic activity of CBO/BMO composites was mainly attributed to the promotion of spatial separation and migration rate of photoproduced electron-hole pairs, enhancement of visible light absorption and more generation of reactive species (•O2-) on the interface of catalyst and water which was demonstrated by nitroblue tetrazolium (NBT) and EPR. Our work indicated that construction of CuBi2O4/Bi2MoO6 p-n heterostructure photocatalyst is a promising environmental friendly alternative method to deal with the biohazards of pathogenic microorganisms.

5.
J Xray Sci Technol ; 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31815728

RESUMO

OBJECTIVE: To investigate the characterization of breast lesions using diffusion kurtosis model-based imaging. METHODS: This prospective study included 120 consecutive patients underwent preoperative DCE-MRI examinations and multi-b-value diffusion-weighted imaging (DWI). Among them, 88 malignant lesions and 44 benign lesions were detected, 56 normal fibroglandular breast tissue were selected as normal control. Conventional apparent diffusion coefficient (ADC), DKI-based parameters mean kurtosis (MK) and mean diffusivity (MD) were analyzed by lesions types and histological subtypes using one-way ANOVA and receiver operating characteristic (ROC) curve. RESULTS: (1) The malignant group showed significantly lower ADC and MD (1.07±0.32×10-3 mm2/s and 1.30±0.40×10-3 mm2/s, respectively) and higher MK (0.87±0.18) than those in the benign group (1.29±0.26×10-3 mm2/s, 1.62±0.31×10-3 mm2/s and 0.67±0.18) and control group (1.67±0.33×10-3 mm2/s, 2.24±0.28×10-3 mm2/s and 0.52±0.08) with all P <  0.001. (2) Areas under ROC curve (AUC) for diagnosing malignant lesions were 0.936 for MD, 0.911 for MK and 0.897 for ADC, respectively. AUC for MD was significantly higher than that for ADC (P = 0.015). The optimal cut-off value, sensitivity, specificity, positive predictive value, negative predictive value and accuracy were as follow: ADC = 1.18×10-3mm2/s, 78.3%, 93.2%, 81.2%, 81.6%, 81.4%; MD = 1.48×10-3mm2/s, 82.2%, 98.3%, 84.4%, 87.8%, 86.2%; MK = 0.78, 91.5%, 85.3%, 89.0%, 85.8%, 87.2%. (3) Invasive ductal carcinoma (IDC), ductal carcinoma in situ (DCIS) and mucinous adenocarcinoma also showed significant differences among ADC, MD and MK (with P <  0.05). CONCLUSIONS: MR-DKI parameters enable to improve breast lesion characterization and have diagnostic potential applying to different pathological subtypes of breast cancers.

6.
J Dev Behav Pediatr ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31764410

RESUMO

OBJECTIVE: The epidemiological studies of Chinese developmental dyslexia (DD) in China are still limited. The current study aimed to investigate the prevalence rate, risk factors, and psychiatric comorbidities of Chinese DD in Guangzhou, a city in South China. METHOD: A total of 1661 students from second to fifth grades were recruited. The dyslexic students were identified by evaluating learning disability through the Pupil Rating Scale-Revised Screening for Learning Disability (PRS) scale by the head teachers and word recognition through the standard test. Students with a PRS score of <65 received the Raven's test, and those with intelligence quotient scores below 80 in the Raven's test were excluded. Psychiatric comorbidities were assessed by the Strength and Difficulties Questionnaire completed by parents. RESULTS: The prevalence rate of Chinese DD was 4.9% in Guangzhou city. There were significant differences in gender, the paternal educational level, and reading experience before the age of 6 years between the DD group and the non-DD group. Male gender (odds ratio [OR] = 4.17), low paternal educational level (p = 0.045), and lack of reading experience before the age of 6 years (OR = 1.99) were the risk factors for DD. The DD cases had a higher risk of hyperactivity and inattention (OR = 3.21). CONCLUSION: This study showed that the prevalence rate of DD was 4.9% in Guangzhou city. Male gender, low paternal educational level, and lack of reading experience before the age of 6 years were the risk factors for Chinese DD. The high comorbidity rate of hyperactivity and inattention in the Chinese DD population needs further evaluation.

7.
J Nurs Adm ; 49(12): 583-585, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31725517

RESUMO

Developing a professional practice model (PPM) is essential for hospitals seeking Magnet designation. The article describes the development and implementation of a PPM in a tertiary hospital that was the 1st hospital in mainland China applying for Magnet recognition. This article provides a framework for hospital administrators who wish to reference a successful process when creating their own Magnet PPMs.


Assuntos
Competência Clínica/normas , Guias como Assunto , Recursos Humanos de Enfermagem no Hospital/normas , Papel Profissional , Qualidade da Assistência à Saúde/normas , Centros de Atenção Terciária/normas , Adulto , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Enfermagem
8.
J Med Virol ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31724212

RESUMO

Achieving hepatitis B e antigen (HBeAg) seroconversion is a satisfactory endpoint during antiviral treatment for chronic hepatitis B (CHB). This study aimed to develop and validate a novel scoring system to predict HBeAg seroconversion during entecavir (ETV) treatment. A total of 526 patients with HBeAg-positive CHB treated with ETV for at least 1 year were randomly assigned to the training and validation cohorts. Baseline parameters including hepatitis B virus DNA, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), and alanine aminotransferase level were quantified. Patients who achieved HBeAg seroconversion were compared with those without HBeAg seroconversion. A prediction model was established to predict HBeAg seroconversion during ETV treatment. After a median follow up of 2.67 years, 93 (36.0%) and 87 (32.5%) patients in the training and validation cohorts developed HBeAg seroconversion. A prediction score composed of age, HBsAg and HBcAb quantification was derived. Areas under receiver operating characteristic curve at 5 years of this prediction score were 0.70 and 0.72 in the training and validation cohorts. By using the dual cutoff values of 0.28 and 0.58, the model was endowed with high sensitivity and specificity to exclude or identify patients developing HBeAg seroconversion (90.3% sensitivity and 90.2% specificity in the training cohort as well as 92.8% sensitivity and 84.4% specificity in the validation cohort, respectively). A novel prediction score that uses baseline clinical variables was developed and validated. The score accurately estimates the probabilities of developing HBeAg seroconversion at 5-years ETV therapy in patients with CHB.

9.
Nucleic Acids Res ; 47(21): 11461-11475, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31647102

RESUMO

Application of CRISPR-based technologies in non-model microorganisms is currently very limited. Here, we reported efficient genome engineering of an important industrial microorganism, Zymomonas mobilis, by repurposing the endogenous Type I-F CRISPR-Cas system upon its functional characterization. This toolkit included a series of genome engineering plasmids, each carrying an artificial self-targeting CRISPR and a donor DNA for the recovery of recombinants. Through this toolkit, various genome engineering purposes were efficiently achieved, including knockout of ZMO0038 (100% efficiency), cas2/3 (100%), and a genomic fragment of >10 kb (50%), replacement of cas2/3 with mCherry gene (100%), in situ nucleotide substitution (100%) and His-tagging of ZMO0038 (100%), and multiplex gene deletion (18.75%) upon optimal donor size determination. Additionally, the Type I-F system was further applied for CRISPRi upon Cas2/3 depletion, which has been demonstrated to successfully silence the chromosomally integrated mCherry gene with its fluorescence intensity reduced by up to 88%. Moreover, we demonstrated that genome engineering efficiency could be improved under a restriction-modification (R-M) deficient background, suggesting the perturbance of genome editing by other co-existing DNA targeting modules such as the R-M system. This study might shed light on exploiting and improving CRISPR-Cas systems in other microorganisms for genome editing and metabolic engineering practices.

10.
Sci Rep ; 9(1): 13948, 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31558731

RESUMO

China has nearly 10% of the general HBV carrier population in the world; this infection is the most common cause of chronic liver disease. Understanding HBV epidemiology is essential for future infection control, evaluation, and treatment. This study determined the prevalence of HBV infection in Shenzhen by serological testing and analysis in 282,166 HBV screening cases for the following: HBcAb, indicative of previous HBV infection; HBsAg, indicative of chronic (current) infection; HBsAb, indicative of immunity from vaccination; and 34,368 HBV etiological screening cases for HBV-DNA, indicative of virus carriage, in which 1,204 cases were genotyped and mutation analyzed for drug-resistance evaluation. Shenzhen was a highly endemic area of HBV throughout the study period (prevalence 9.69%). HBV infections were almost entirely in the 20 and older age groups with a male-to-female ratio of 1.16:1 which is approximately the same as the male-to-female ratio of the general population in China. However, only 71.25% of the general population retained HBV immune protection. Genotype B and C were identified as the most common agents; recombinant B/C and B/D also existed; some cases, however, could not be genotyped. NAs resistant mutation occurrence patterns were multitudinous; single mutation patterns of rtM204I/V and rtL180M occurrences accounted for majority, followed by the combinational mutation pattern L180M + M204I/V. Drug-resistance was prevalent, mainly occurring in the cross resistance patterns LAM + LdT and LAM + LdT + ETV, and significantly more critical in males. These results demonstrate that all people free from HBV infection should obtain injections of the vaccine or booster shots, and conventional virologic detection in a clinical laboratory center should incorporate genotype and mutation alongside the serological factors for etiology and develop better classification methods, such as sequencing.

11.
J Infect Dis ; 220(9): 1469-1476, 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31370059

RESUMO

BACKGROUND: Little is known about cause and intervention for alanine aminotransferase (ALT) elevation after complete viral suppression in patients with chronic hepatitis B (CHB). METHODS: In this prospective cohort study, patients with CHB who were treated with nucleos(t)ide analogs and maintained undetectable levels of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) for at least 6 months were enrolled. Patients were followed up at 6-month intervals, and anthropometric, biochemical, and virological assessments were performed. RESULTS: Of 1965 patients with median follow-up of 18.36 months, one third of patients experienced ALT elevation. Baseline high body mass index ([BMI] defined as ≥25 kg/m2), younger age, and liver cirrhosis independently increased the risk of longitudinal ALT elevation. At the end of follow-up, 89 (4.8%) patients reverted to low BMI, and 92 (5.0%) developed to high BMI. Compared with persistent high BMI, reversion to low BMI reduced the risk of ALT elevation (adjusted odds ratio [aOR], 0.38; 95% confidence interval [CI], 0.19-0.77); compared with persistent low BMI, onset of high BMI increased the risk of ALT elevation (aOR, 1.78; 95% CI, 1.02-3.11). CONCLUSIONS: High BMI is an independent predictor for ALT elevation after complete HBV DNA suppression. Improvement of BMI may have a beneficial effect on ALT normalization and even long-term outcomes.

12.
Chin Med J (Engl) ; 132(17): 2039-2045, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31425273

RESUMO

BACKGROUND: With the publication of Sepsis-3 definition, epidemiological data based on Sepsis-3 definition from middle-income countries including China are scarce, which prohibits understanding of the disease burden of this newly defined syndrome in these settings. The purpose of this study was to describe incidence and outcome of Sepsis-3 in Yuetan sub-district of Beijing and to estimate the incidence rate of Sepsis-3 in China. METHODS: The medical records of all adult residents hospitalized from July 1, 2012 to June 30, 2014 in Yuetan sub-district of Beijing were reviewed. Patients with sepsis-3 and severe sepsis/septic shock were identified. The incidence rates and mortality rate of sepsis-3 and sepsis/septic shock were calculated, incidence rates and in-hospital mortality rates were normalized to the population distribution in the 2010 National Census. Population incidence rate and case fatality rate between sexes were compared with the Z test, as the data conformed to Poisson distribution. RESULTS: Of the 21,191 hospitalized patients, 935 patients were diagnosed with Sepsis-3, and 498 cases met severe sepsis/septic shock criteria. The crude annual incidence rate of Sepsis-3 in Yuetan sub-district was 363 cases per 100,000 population, corresponding to standardized incidence rates of 236 cases per 100,000 population per year, respectively. The overall case fatality rate of Sepsis-3 was 32.0%, the crude population mortality rates of Sepsis-3 was 116 cases per 100,000 population per year, the standardized mortality rate was 67 cases per 100,000 population per year, corresponding to a speculative extrapolation of 700,437 deaths in China. The incidence rate and mortality rate of Sepsis-3 were significantly higher in males, elderly people, and patients with more comorbidities. The 62.1% of patients with Sepsis-3 had community-acquired infections, compared with 75.3% of infected patients without Sepsis-3 (P < 0.001). The most common infection in patients with Sepsis-3 was lower respiratory tract infection. When compared with patients with Sepsis-3, patients diagnosed as severe sepsis/septic shock were more likely to have higher case fatality rate (53.4% vs. 32.0%, P < 0.001) CONCLUSIONS:: This study found the standardized incidence rate of 236 cases per 100,000 person-year for Sepsis-3, which was more common in males and elderly population. This corresponded to about 2.5 million new cases of Sepsis-3 per year, resulting in more than 700,000 deaths in China. CLINICAL TRIAL REGISTRATION: NCT02285257, https://clinicaltrials.gov/ct2/show/record/NCT02285257.

13.
Cancer Cell Int ; 19: 215, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31452627

RESUMO

Background: The long non-coding RNA H19 plays critical roles in cancer occurrence, development, and progression. The present study is for the first time to evaluate the association of genetic variations in the H19 promoter region with advanced colorectal cancer (CRC) susceptibility, environmental factors, and clinical outcomes. Methods: 16 single-nucleotide polymorphisms (SNPs) were identified in the H19 gene promoter by DNA sequencing, and 3 SNPs among which including rs4930101, rs11042170, and rs2735970 further expanded samples with 572 advanced CRC patients and 555 healthy controls. Results: We found that harboring SNP [rs4930101 (P = 0.009), rs2735970 (P = 0.003), and rs11042170 (P = 0.003)] or carrying more than one combined risk genotypes significantly increased the risk for CRC [P < 0.0001, adjusted OR (95% CI) 6.48 (2.97-14.15)]. In the correlation analysis with environmental factors, rs2735970 and gender, combined risk genotypes (> 1 vs. ≤ 1) and family history of cancer demonstrated significant interactions. Furthermore, a remarkably worse clinical outcome was found in combined risk genotypes (> 1 vs. ≤ 1), especially in CRC patients with body weight ≥ 61 kg, smoking, and first-degree family history of cancer (Log-rank test: P = 0.006, P = 0.018, and P = 0.013, respectively). More importantly, the multivariate Cox regression analyses further verified that combined risk genotypes > 1 showed a prognostic risk factor for CRC patients with body weight ≥ 61 kg (P = 0.002), smoking (P = 0.008), and family history of cancer (P = 0.006). In addition, MDR analysis consistently revealed that the combination of selected SNPs and nine known risk factors showed a better prediction prognosis and represented the best model to predict advanced CRC prognosis. Conclusion: 3 SNPs of rs4930101, rs11042170, and rs27359703 among 16 identified SNPs of H19 gene remarkably increased CRC risk. Furthermore, the combined risk genotypes had a significant impact on environmental factors and clinical outcomes in the advanced CRC patients with body weight ≥ 61 kg, ever-smoking, and first-degree family history of cancer. These data suggest that H19 promoter SNPs, especially these combined SNPs might be more potentially functional biomarkers in the prediction of advanced CRC risk and prognosis.

14.
Mol Cancer Res ; 17(11): 2244-2256, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31467112

RESUMO

ZEB1 (a positive enhancer) and KLF5 (a negative silencer) affect transcription factors and play inherently conserved roles in tumorigenesis and multidrug resistance. In humans, the rs2295080T-allele at the mTOR promoter locus has been associated with human cancer risk; however, the 63 bp spacing of another SNP rs2295079 has not been identified. Here, we discovered, for the first time, that rs2295079 (-78C/G) and rs2295080 (-141G/T) formed linkage haplotypes, with Ht1 (-78C/-141G) and Ht2 (-78G/-141T) being dominant, which were associated with distinct susceptibility to breast cancer, response to paclitaxel, and clinical outcomes in breast cancer. At the cellular level, compared with Ht1, Ht2 exhibits a much stronger effect on promoting mTOR expression, leading to enhanced tumor cell growth and strengthened resistance to PTX treatment. Mechanistically, the -141T allele of Ht2 creates a novel ZEB1-binding site; meanwhile, the -78C allele of Ht1 exists as an emerging KLF5-binding site, which synergistically induces promote/inhibit mTOR expression, cell proliferation, and excretion of cytotoxic drugs through the ZEB1/KLF5-mTOR-CCND1/ABCB1 cascade, thereby affecting the response to paclitaxel treatment in vivo and in vitro. Our results suggest the existence of a ZEB1/KLF5-mTOR-CCND1/ABCB1 axis in human cells that could be involved in paclitaxel response pathways and functionally regulate interindividualized breast cancer susceptibility and prognosis. IMPLICATIONS: This study highlights the function of haplotypes of mTOR -78C/-141G and -78G/-141T, in affecting breast cancer susceptibility and paclitaxel response regulated by ZEB1/KLF5-mTOR-CCND1/ABCB1 axis.

15.
Nanotechnology ; 30(43): 435403, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31342936

RESUMO

Herein, a carbon membrane and Au nanoparticles were combined to improve the efficiency of photoelectrocatalytic water splitting over a TiO2 nanotube arrays film (TiO2 NTAF). Two different ternary nanostructures were constructed by hydrothermal and photochemical deposition processes. One was carbon membrane bridged Au nanoparticles and TiO2 nanotube arrays (Au/C/TiO2 NTAF), while the other was Au nanoparticles sandwiched between carbon membrane and TiO2 nanotube arrays (C/Au/TiO2 NTAF). The two structures exhibited enhanced visible light harvesting ability, but they showed distinctly different photoelectric properties. The unique microstructure of C/Au/TiO2 NTAF resulted in a much higher reduction of the electron cloud density of Au nanoparticles as carrier recombination centers, which were responsible for its poor photoelectrochemical performance. However, a champion photocurrent of Au/C/TiO2 NTAF was observed (0.984 mA cm-2), indicating superior ability of the photoelectrocatalytic water splitting. The great enhancement was attributed to multiple carriers transport paths, which can efficiently utilize the sensitization of the carbon membrane and the surface plasmon resonance effect of the Au nanoparticles.

16.
J Cancer ; 10(16): 3593-3607, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31333776

RESUMO

A systematical bioinformatics and meta-analysis were carried out to establish our understanding of possible relationships between DNA repair genes and the development of cancer. The bioinformatics analysis confirmed that lower XPA and XPC levels and higher XPD, XPF, and WRN levels were observed in 19 types of cancer, and subsequently results indicated that elevated XPA and XPC had a better impact on overall survival, however, higher XPD, XPF, and WRN showed worse influence on cancer prognosis. The meta-analysis included 58 eligible studies demonstrated that harboring XPA rs10817938, XPD rs238406 increased overall cancer risk, however, XPA rs2808668 SNP in overall cancer analysis and XPF rs3136038 in the digestive system remarkably reduced the cancer risk. Moreover, no correlation was investigated for XPC rs1870134, WRN rs1346044 and rs1801195. These suggest that the DNA repair gene was associated with carcinogenesis, and contribute to the prognosis, and the critical SNPs further involved in affecting cancer risk.

17.
Cancer Biother Radiopharm ; 34(8): 504-510, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31295003

RESUMO

Objectives: The present study aimed to retrospectively compare the clinical and imaging characteristics and laboratory data of patients with malignant tumor concurrent with acute ischemic stroke (IS) and patients with cerebral infarction only, and to analyze the potential related risk factors. Method: A total of 126 patients with acute cerebral infarction concurrent with malignant tumor were collected and assigned to the malignant tumor group. In addition, 120 patients hospitalized for routine acute IS during the same period were randomly selected as the control group. Demographic data and common risk factors of cerebrovascular disease, laboratory data, and imaging characteristics in these two groups were compared. Results: In the malignant tumor group, the age of onset was relatively low, and the National Institutes of Health Stroke Scale score, 90 d recurrence rate, and fatality rate were higher than for those in the control group (p < 0.05). However, most patients had no traditional risk factors of stroke. Biochemical results revealed that the peripheral hemoglobin of patients with malignant tumor and cerebral infarction was lower than for those in the control group (p < 0.05). Furthermore, the levels of D-dimer, fibrinogen, tumor markers CA125, CA199, and carcinoembryonic antigen were significantly elevated, and the difference was statistically significant (p < 0.05). Magnetic resonance imaging results revealed that multiple intracranial infarcts were more common in patients in the malignant tumor group, and the difference was statistically significant compared with patients with cerebral infarction only (p < 0.05). Conclusion: Patients with cancer and IS had fewer traditional stroke risk factors but more anemia as well as higher D-dimer level, tumor marker rate, short-term mortality, and stroke recurrence rate. Furthermore, lower age of onset and other characteristics, including multiple intracranial infarcts, can be regarded as important characteristics of such patients.

18.
Enzyme Microb Technol ; 129: 109356, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31307580

RESUMO

Kumamolisin from Alicyclobacillus sendaiensis strain NTAP-1 is a serine protease with collagenase activity. After molecular engineering, a kumamolisin mutant, named Kuma030, was obtained with high proteolytic activity against gluten, which might cause celiac disease. Kuma030 exhibited its potential application in industrial and medicine, while challenges remained of its large-scale purification and production. In the studies here, we successfully overexpressed the Kuma030 in E. coli BL21 (DE3) by anchoring a SUMO (Small Ubiquitin-like Modifier) fusion protein at its N-terminal end. In addition, a fast protein purification procedure was developed according to the acidophilic and thermophilic properties of Alicyclobacillus sendaiensis. After a simple acid treatment followed by a heat treatment, a total of 9.9 mg functional Kuma030 was quickly obtained form 1 L LB media culture. This purified Kuma030 was confirmed to be functional to cleave the PQ sequences in a designed protein substrate, and the gluten in actual food samples, such as whole wheat bread and beer, in a fast manner. Our studies provided an efficient strategy for the overexpression and purification of functional Kuma030 in E. coli, which might expand its broad practical applications.


Assuntos
Alicyclobacillus/enzimologia , Proteínas de Bactérias/metabolismo , Escherichia coli/metabolismo , Glutens/metabolismo , Hidrolases/metabolismo , Alicyclobacillus/genética , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Estabilidade Enzimática , Escherichia coli/genética , Temperatura Alta , Hidrolases/química , Hidrolases/genética
19.
J Thorac Dis ; 11(5): 2034-2042, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31285896

RESUMO

Background: We aimed to evaluate the accuracy of quick Sequential (sepsis-related) Organ Failure Assessment (qSOFA) for the diagnosis of sepsis-3, and to analyze the prognosis of infected patients in wards over-diagnosed with qSOFA but missed by sepsis-3, and those missed by qSOFA but in accordance with sepsis-3 criteria. We also intended to validate the performance of qSOFA as one predictor of outcome in patients with suspicion of infection. Methods: We reviewed the medical records of 1,716 adult patients with infection who were hospitalized from July 1st, 2012 to June 30th, 2014 in the Yuetan subdistrict of Beijing, China. Based on the sepsis-3 criteria and qSOFA score proposed by the Third International Consensus Definitions for Sepsis and Septic Shock, these patients were categorized into four groups: qSOFA(-)sepsis(-), qSOFA(+)sepsis(-), qSOFA(-)sepsis(+), and qSOFA(+)sepsis(+). Multivariate logistic regression analysis was used to determine the independent risk factors for in-hospital mortality. The area under the receiver operating characteristic curves (AUROCs) of the qSOFA(+) group were compared with the sepsis(+) group for in-hospital mortality, ICU admission, and invasive ventilation. Results: Among the 1,716 patients with infection, there were 935 patients (54.5%) with sepsis, and 640 patients (37.3%) with qSOFA ≥2. There were 610 patients in the qSOFA(-)sepsis(-) group, 171 in the qSOFA(+)sepsis(-) group, 466 in the qSOFA(-)sepsis(+) group, and 469 in the qSOFA(+)sepsis(+) group. In the logistic regression analysis, increasing age, bedridden status, and malignancy were all independent risk factors of hospital mortality. Sepsis and qSOFA ≥2 were also independent risk factors of hospital mortality, with an adjusted OR of 3.85 (95% CI: 2.70-5.50) and 13.92 (95% CI: 9.87-16.93) respectively. qSOFA had a sensitivity of 50.2% and a specificity of 78.1% for sepsis-3. The false-positive [qSOFA(+)sepsis(-)] group had 38 patients (22.2%) die during hospitalization, and an adjusted OR of 9.20 (95% CI: 4.86-17.38). In addition, the false-negative [qSOFA(-)sepsis(+)] group had a hospital mortality rate of 7.3% (34/466) and an adjusted OR of 2.59 (95% CI: 1.39-4.83). In comparison, patients meeting neither qSOFA nor sepsis criteria had the lowest hospital mortality [2.6% (16/610)], whereas patients with both qSOFA ≥2 and sepsis had the highest hospital mortality [56.5% (265/469)], with an adjusted OR of 42.02 (95% CI: 24.31-72.64). The discrimination of in-hospital mortality using qSOFA (AUROC, 0.846; 95% CI, 0.824-0.868) was greater compared with sepsis-3 criteria (AUROC, 0.834; 95% CI, 0.805-0.863; P<0.001). Conclusions: In our analysis, the sensitivity(Se) of qSOFA for the diagnosis of sepsis was lower, and qSOFA score ≥2 might identify a group of patients at a higher risk of mortality, regardless of being septic or not.

20.
Nat Commun ; 10(1): 1802, 2019 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-30996254

RESUMO

The primary cause of heart failure is the loss of cardiomyocytes in the diseased adult heart. Previously, we reported that the miR-17-92 cluster plays a key role in cardiomyocyte proliferation. Here, we report that expression of miR-19a/19b, members of the miR-17-92 cluster, is induced in heart failure patients. We show that intra-cardiac injection of miR-19a/19b mimics enhances cardiomyocyte proliferation and stimulates cardiac regeneration in response to myocardial infarction (MI) injury. miR-19a/19b protected the adult heart in two distinctive phases: an early phase immediately after MI and long-term protection. Genome-wide transcriptome analysis demonstrates that genes related to the immune response are repressed by miR-19a/19b. Using an adeno-associated virus approach, we validate that miR-19a/19b reduces MI-induced cardiac damage and protects cardiac function. Finally, we confirm the therapeutic potential of miR-19a/19b in protecting cardiac function by systemically delivering miR-19a/19b into mice post-MI. Our study establishes miR-19a/19b as potential therapeutic targets to treat heart failure.


Assuntos
Terapia Genética/métodos , Insuficiência Cardíaca/patologia , MicroRNAs/administração & dosagem , MicroRNAs/metabolismo , Infarto do Miocárdio/terapia , Animais , Proliferação de Células/genética , Dependovirus/genética , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Vetores Genéticos/administração & dosagem , Vetores Genéticos/genética , Insuficiência Cardíaca/terapia , Ventrículos do Coração/patologia , Humanos , Injeções Intralesionais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/patologia , Miócitos Cardíacos/fisiologia , Regeneração/genética
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