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2.
J Microbiol Methods ; 217-218: 106888, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38176658

RESUMO

Timely bacterial identification (ID) and antimicrobial susceptibility testing (AST) are of significance for therapy of bacteria-infected patients. In the present study, we developed a multiplex TaqMan qPCR assay for rapid and accurate ID and AST of three common hospital acquired pneumonia species, namely Acinetobacter baumannii, Klebsiella pneumoniae and Staphylococcus aureus. In this assay, DNA extraction and bacterial co-incubation with antibiotics are accomplished based on a common PCR instrument. ID of three bacteria is based on specific conserved DNA sequence fragment (gltA for A. baumannii, phoE for K. pneumoniae and nuc for S. aureus) detection through multiplex TaqMan qPCR assay within 80 min. AST of three bacteria could be acquired within 200 min based on genomic DNA fold change detection after 2 h of antibiotic exposure. Testing of 23 bronchoalveolar lavage fluid samples spiked by different A. baumannii isolates, 20 bronchoalveolar lavage fluid samples spiked by different K. pneumoniae isolates, and 14 bronchoalveolar lavage fluid samples spiked by different S. aureus isolates showed that the multiplex TaqMan qPCR assay had 100% (95% CI: 85.69-100), 100% (95% CI: 83.89-100) and 100% (95% CI:78.47-100) identification agreement with the initial spiked bacteria. Subsequent AST results compared with the standard broth microdilution method showed an overall agreement of 91.30% (95% CI: 73.20 to 97.58) for A. baumannii, 90% (95% CI: 69.90 to 97.21) for K. pneumoniae and 92.86% (95% CI: 68.53 to 98.73) for S. aureus based on the current multiplex TaqMan assay. Due to the high rapidity, good agreement, simplicity, and high throughput, this multiplex TaqMan assay could be helpful for ID and broad-spectrum AST in A. baumannii, K. pneumoniae and S. aureus, as well as potentially applicable for other clinical bacteria by changing the primers and probes.


Assuntos
Infecções Estafilocócicas , Staphylococcus aureus , Humanos , Staphylococcus aureus/genética , Antibacterianos/farmacologia , Bactérias/genética , DNA , Testes de Sensibilidade Microbiana , Reação em Cadeia da Polimerase Multiplex/métodos
3.
Andrology ; 12(1): 222-230, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37222247

RESUMO

BACKGROUND: It has been shown that methylation in the promoter region of eNOS can downregulate eNOS expression resulting in the endothelial dysfunction. However, it is unclear whether low androgen levels and type 1 diabetes cause ED by methylating the promoter region of eNOS in the penile corpus cavernosum. OBJECTIVE: To clarify the effects of type 1 diabetes and hypo-androgen status on the methylation level of the promoter region of the eNOS gene in penile cavernous tissue and their relationship with the erectile function. METHODS: Fifty-eight eight-week-old male Sprague-Dawley rats were randomly divided into six groups (n = 6): sham operation group, castration group, castration+testosterone (cast+T) group, normoglycemia group, diabetic group, and diabetic+methyltransferase inhibitor (5-aza-dc, 1.5 mg/kg) group. The ICPmax/MAP, serum T, the concentration of nitric oxide (NO), the expression of DNMT1, DNMT3a, DNMT3b, and eNOS, and the methylation level of the eNOS promoter region in penile corpus cavernosum of rat were examined 4 weeks after surgery in the sham-operated group, the castration group, and the castration + testosterone replacement group. Those tests were examined after 6 weeks using of methylation inhibitors in the normoglycemic group, the diabetic group, and the diabetic + methylation inhibitor group. RESULTS: ICPmax/MAP, DNMT1, DNMT3a, DNMT3b, eNOS, and NO levels were significantly lower in castrated rats than in sham and cast+T rats (P < 0.05). ICPmax/MAP, eNOS, and NO levels were lower, and DNMT1, DNMT3a, and DNMT3b expression levels were significantly increased in the diabetic group compared with the normoglycemic and diabetic+methyltransferase inhibitor groups (P < 0.05). There was no significant difference in the methylation level of the promoter region of eNOS in penile cavernous tissue of castrated rats compared with the sham group or the testosterone replacement group. The methylation level of the promoter region of eNOS in penile cavernous tissue was significantly higher in the diabetic group than in the normoglycemic group and diabetic+methyltransferase inhibitor group (P < 0.05). CONCLUSION: Although low androgen status inhibited the level of methyltransferase in rat penile cavernous tissue, did not affect the level of methylation in the promoter region of eNOS. Hyperglycemia inhibits the NO level in the penile cavernous tissue and the erectile function of rats by upregulating the methyltransferase level in the penile cavernous tissue and the methylation level in the promoter region of eNOS. Methylation inhibitors can partly improve the erectile function in type 1 diabetic rats.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Disfunção Erétil , Animais , Masculino , Ratos , Androgênios/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 1/complicações , Disfunção Erétil/etiologia , Metilação , Metiltransferases/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Orquiectomia/efeitos adversos , Ereção Peniana , Pênis/metabolismo , Ratos Sprague-Dawley , Testosterona
4.
Front Genet ; 14: 1219898, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37576557

RESUMO

Tomato (Solanum lycopersicum) is widely cultivated and consumed worldwide. Tomato leaf mold, caused by Cladosporium fulvum, is one of the most devastating diseases in tomato production. At present, some tomato leaf mold resistance (Cf series) genes used in production gradually lose resistance due to the continuous and rapid differentiation of C. fulvum physiological races. The Cf-16 gene derived from the "Ontario7816" tomato cultivar has shown effective resistance in field trials for many years, but few studies have reported on the mapping of the Cf-16 gene, which has not been cloned, limiting its utilization in tomato breeding. Here, we mapped Cf-16 using a novel comprehensive strategy including bulk segregation analysis (BSA), genome resequencing and SSR molecular markers. A genetic analysis revealed that Cf-16 resistance in "Ontario7816" is controlled by one major dominant locus. The Cf-16 gene was mapped in a region of 2.6 cM at chromosome 6 between two markers, namely, TGS447 and TES312, by using an F2 population from a cross between the resistant cultivar "Ontario7816" and susceptible line "Moneymaker." Two nucleotide-binding-site-leucine-rich repeat (NBS-LRR) resistance genes, namely, XM_004240667.3 and XM_010323727.1, were identified in this interval. They are strong candidates for the Cf-16 gene. The mapping of Cf-16 may speed up its utilization for breeding resistant tomato varieties and represents an important step forward in our understanding of the mechanism underlying resistance to tomato leaf mold.

5.
Microbiol Spectr ; 11(4): e0034123, 2023 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-37260382

RESUMO

Synergistic effects of phages in combination with antibiotics have received increasing attention. In this present study, we isolated a new phage pB3074 against clinically isolated multidrug-resistant Acinetobacter baumannii. Phage pB3074 combined with cell wall-targeting antibiotics could produce synergistic antibacterial effect in vitro bactericidal activities. Further research indicates that the bacteriophage dose is critical to synergistic antimicrobial effect of phage and antibiotic combination. Cefotaxime and meropenem were selected as the representative cell wall-targeting antibiotics for further synergistic antibacterial study. Results illustrated that phage pB3074 and cefotaxime or meropenem combination was very effective for the removal of mature biofilm and inhibition of biofilm formation. In a pig skin explant model, results also showed that phage pB3074 and cefotaxime or meropenem combination was very effective for the treatment of wound infection ex vivo. Subsequent studies showed that some extent recovery of drug sensitivity to cell wall-targeting antibiotics might be vital mechanism of synergistic antibacterial effect between bacteriophage pB3074 and these antibiotics. The existence of antibiotics could promote phage adsorption and proliferation, which might also be potential mechanism for synergistic antibacterial activities and have been observed in cefotaxime and meropenem application. In summary, results in the current study demonstrated that phage pB3074 has the potential to be developed as an antibacterial agent and combined application of phages and antibiotics might be a new choice for the treatment of current multidrug-resistant bacterial infections. IMPORTANCE Combined application of phages and antibiotics cannot only effectively inhibit the appearance of phage-resistant bacteria, but also reduce the effective use concentration of antibiotics, and even make some bacteria regain sensitivity to some resistant antibiotics. Therefore, phage-antibiotic combination (PAC) could improve the antibacterial activity of individual drug, providing a new choice for clinical treatment of multidrug-resistant bacterial infections.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Bacteriófagos , Animais , Suínos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Meropeném/farmacologia , Sinergismo Farmacológico , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Cefotaxima/farmacologia , Farmacorresistência Bacteriana Múltipla , Testes de Sensibilidade Microbiana
6.
IEEE J Biomed Health Inform ; 26(11): 5344-5354, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35951561

RESUMO

A novel coronavirus disease (COVID-19) is a pandemic disease has caused 4 million deaths and more than 200 million infections worldwide (as of August 4, 2021). Rapid and accurate diagnosis of COVID-19 infection is critical to controlling the spread of the epidemic. In order to quickly and efficiently detect COVID-19 and reduce the threat of COVID-19 to human survival, we have firstly proposed a detection framework based on reinforcement learning for COVID-19 diagnosis, which constructs a mixed loss function that can integrate the advantages of multiple loss functions. This paper uses the accuracy of the validation set as the reward value, and obtains the initial model for the next epoch by searching the model corresponding to the maximum reward value in each epoch. We also have proposed a prediction framework that integrates multiple detection frameworks using parameter sharing to predict the progression of patients' disease without additional training. This paper also constructed a higher-quality version of the CT image dataset containing 247 cases screened by professional physicians, and obtained more excellent results on this dataset. Meanwhile, we used the other two COVID-19 datasets as external verifications, and still achieved a high accuracy rate without additional training. Finally, the experimental results show that our classification accuracy can reach 98.31%, and the precision, sensitivity, specificity, and AUC (Area Under Curve) are 98.82%, 97.99%, 98.67%, and 0.989, respectively. The accuracy of external verification can reach 93.34% and 91.05%. What's more, the accuracy of our prediction framework is 91.54%. A large number of experiments demonstrate that our proposed method is effective and robust for COVID-19 detection and prediction.


Assuntos
COVID-19 , Aprendizado Profundo , Humanos , COVID-19/diagnóstico por imagem , Teste para COVID-19 , Tomografia Computadorizada por Raios X/métodos , Pandemias
7.
Microbiol Spectr ; 10(4): e0009622, 2022 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-35736241

RESUMO

Phage-antibiotic combination (PAC) therapy is a potential new alternative to treat infections caused by pathogenic bacteria, particularly those caused by antibiotic-resistant bacteria. In the present study, phage YC#06 against highly multidrug-resistant Acinetobacter baumannii 4015 was isolated, identified, and characterized. Compared with antibiotics alone, the time-kill experiments in vitro showed that YC#06 and antibiotic mixtures that include the chloramphenicol, imipenem, and cefotaxime combination could produce phage-antibiotic synergy (PAS), which reduced the ultimate effective concentration of antibiotics. No phage-resistant bacteria have been isolated during the whole time-kill experiments in vitro. Of note, PAS was dose dependent, requiring a moderate phage dose to achieve maximum PAS effect. In addition, PAS could effectively inhibit biofilm formation and remove mature biofilms in vitro. Furthermore, PAS between the combination of YC#06 and antibiotic mixtures in vivo was validated using a zebrafish infection model. Overall, the results of this study demonstrate that PAC could be a viable strategy to treat infection caused by high-level multidrug-resistant Acinetobacter baumannii or other drug-resistant bacteria through switching to other types of phage and antibiotic mixtures. IMPORTANCE The treatment of multidrug-resistant bacterial infection is an urgent clinical problem. The combination of bacteriophages and antibiotics could produce synergistic bactericidal effects, which could reduce the emergence of antibiotic resistance and antibiotic consumption in antibiotic-sensitive bacteria, restore efficacy to antibiotics in antibiotic-resistant bacteria, and prevent the occurrence of phage-resistant bacteria. Phage-antibiotic combination (PAC) might be a potential new alternative for clinical treatment of multidrug-resistant bacterial infections.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Bacteriófagos , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Sinergismo Farmacológico , Testes de Sensibilidade Microbiana , Peixe-Zebra
8.
J Occup Environ Med ; 63(9): e641-e649, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34491972

RESUMO

According to the decibel level of noise detection in the working environment, the research objects were divided into high noise group (more than 85 dB), low noise group (55 to 85 dB), and control group (less than 55 dB), the neurobehavioral core test battery (NCTB) was used to systematic tests all workers, radioimmunoassay was used to detect plasma catecholamine levels, and the relationship between noise intensities and the levels of plasma catecholamine was analyzed by canonical correlation. The result shows noise exposure will affect workers' neurological function and the influence of noise on neurobehavioral function may be related to the increase of the levels of norepinephrine and dopamine in the plasma and the inhibition of the synthesis of epinephrine of noise-exposed workers.


Assuntos
Ruído Ocupacional , Exposição Ocupacional , Catecolaminas , Epinefrina , Humanos , Testes Neuropsicológicos , Ruído , Ruído Ocupacional/efeitos adversos , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise
9.
Stem Cell Res Ther ; 12(1): 409, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34271976

RESUMO

BACKGROUND: Tubulointerstitial fibrosis (TIF) is one of the main pathological features of various progressive renal damages and chronic kidney diseases. Mesenchymal stromal cells (MSCs) have been verified with significant improvement in the therapy of fibrosis diseases, but the mechanism is still unclear. We attempted to explore the new mechanism and therapeutic target of MSCs against renal fibrosis based on renal proteomics. METHODS: TIF model was induced by adenine gavage. Bone marrow-derived MSCs was injected by tail vein after modeling. Renal function and fibrosis related parameters were assessed by Masson, Sirius red, immunohistochemistry, and western blot. Renal proteomics was analyzed using iTRAQ-based mass spectrometry. Further possible mechanism was explored by transfected galectin-3 gene for knockdown (Gal-3 KD) and overexpression (Gal-3 OE) in HK-2 cells with lentiviral vector. RESULTS: MSCs treatment clearly decreased the expression of α-SMA, collagen type I, II, III, TGF-ß1, Kim-1, p-Smad2/3, IL-6, IL-1ß, and TNFα compared with model rats, while p38 MAPK increased. Proteomics showed that only 40 proteins exhibited significant differences (30 upregulated, 10 downregulated) compared MSCs group with the model group. Galectin-3 was downregulated significantly in renal tissues and TGF-ß1-induced rat tubular epithelial cells and interstitial fibroblasts, consistent with the iTRAQ results. Gal-3 KD notably inhibited the expression of p-Akt, p-GSK3ß and snail in TGF-ß1-induced HK-2 cells fibrosis. On the contrary, Gal-3 OE obviously increased the expression of p-Akt, p-GSK3ß and snail. CONCLUSION: The mechanism of MSCs anti-renal fibrosis was probably mediated by galectin-3/Akt/GSK3ß/Snail signaling pathway. Galectin-3 may be a valuable target for treating renal fibrosis.


Assuntos
Células-Tronco Mesenquimais , Adenina/toxicidade , Animais , Transição Epitelial-Mesenquimal , Fibrose , Galectina 3/genética , Glicogênio Sintase Quinase 3 beta/genética , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Transdução de Sinais , Fator de Crescimento Transformador beta1
10.
Andrologia ; 52(7): e13627, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32352595

RESUMO

The aim of our study was to investigate whether low androgen level inhibits the erectile function of rats by regulating the expression of P2X receptors. Thirty-six 8-week-old male SD rats were randomly divided into six groups: sham-operated groups (4w-sham, 8w-sham), castration groups (4w-cast, 8w-cast) and androgen replacement after castration groups (4w-cast + T, 8w-cast + T). The maximum intracavernous pressure/mean arterial pressure (ICPmax/MAP), the levels of serum testosterone (T) and nitric oxide (NO), and the expression of P2X1, P2X2, P2X3, eNOS, p-eNOS, ROCK1 and ROCK2 in the cavernous tissue of rats were determined. The serum T, ICPmax/MAP and NO levels in penile corpus cavernosum in the castration groups were significantly lower than those in other groups (p < .01). The protein expression of P2X1, P2X2, P2X3, ROCK1 and ROCK2 in the castration groups was significantly higher than those in other groups (p < .01). P-eNOS/eNOS of the castration groups were significantly lower than those of other groups (p < .01). The serum T level was negatively correlated with the expression of P2X1, P2X2 and P2X3 in the corpus cavernosum. Low androgen level inhibits erectile function by up-regulating the expression of P2X1, P2X2, P2X3 and RhoA/Rho-kinase resulting in reducing the ratio of p-eNOS/eNOS and the level of NO in corpus cavernosum of rats.


Assuntos
Androgênios , Disfunção Erétil , Animais , Humanos , Masculino , Óxido Nítrico Sintase Tipo III , Ereção Peniana , Pênis , Ratos , Ratos Sprague-Dawley , Quinases Associadas a rho
11.
J Cell Mol Med ; 24(10): 5555-5564, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32270599

RESUMO

The role of long non-coding RNAs (lncRNAs) in kidney diseases has been gradually discovered in recent years. LINC00963, as an lncRNA, was found to be involved in chronic renal failure. However, the role and molecular mechanisms of LINC00963 engaged in acute kidney injury (AKI) were still unclear. In this study, we established rat AKI models by ischaemia and reperfusion (I/R) treatment. Urea and creatinine levels were determined, and histological features of kidney tissues were examined following HE staining. CCK8 assay was chosen to assess the viability of hypoxia-induced HK-2 cells. Dual-luciferase reporter gene assays were performed to verify the target relationship between LINC00963 and microRNA. The mRNA and protein levels were assayed by RT-qPCR and Western blot, respectively. Annexin V-FITC/PI and TUNEL staining were used to evaluate apoptosis. LINC00963 was highly expressed in the cell and rat models, and miR-128-3p was predicted and then verified as a target gene of LINC00963. Knockdown of LINC00963 reduced acute renal injury both in vitro and in vivo. LINC00963 activated the JAK2/STAT1 pathway to aggravate renal I/R injury. LINC00963 could target miR-128-3p to reduce G1 arrest and apoptosis through JAK2/STAT1 pathway to promote the progression of AKI.


Assuntos
Injúria Renal Aguda/genética , Injúria Renal Aguda/metabolismo , Janus Quinase 2/metabolismo , MicroRNAs/genética , RNA Longo não Codificante/genética , Fator de Transcrição STAT1/metabolismo , Injúria Renal Aguda/patologia , Animais , Apoptose/genética , Linhagem Celular , Técnicas de Inativação de Genes , Masculino , Ratos
12.
BMC Plant Biol ; 20(1): 33, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31959099

RESUMO

BACKGROUND: Leaf mold disease caused by Cladosporium fulvum is a serious threat affecting the global production of tomato. Cf genes are associated with leaf mold resistance, including Cf-16, which confers effective resistance to leaf mold in tomato. However, the molecular mechanism of the Cf-16-mediated resistance response is largely unknown. RESULTS: We performed a comparative transcriptome analysis of C. fulvum-resistant (cv. Ontario7816) and C. fulvum-susceptible (cv. Moneymaker) tomato cultivars to identify differentially expressed genes (DEGs) at 4 and 8 days post inoculation (dpi) with C. fulvum. In total, 1588 and 939 more DEGs were found in Cf-16 tomato than in Moneymaker at 4 and 8 dpi, respectively. Additionally, 1350 DEGs were shared between the 4- and 8-dpi Cf-16 groups, suggesting the existence of common core DEGs in response to C. fulvum infection. The up-regulated DEGs in Cf-16 tomato were primarily associated with defense processes and phytohormone signaling, including salicylic acid (SA) and jasmonic acid (JA). Moreover, SA and JA levels were significantly increased in Cf-16 tomato at the early stages of C. fulvum infection. Contrary to the previous study, the number of up-regulated genes in Cf-16 compared to Cf-10 and Cf-12 tomatoes was significantly higher at the early stages of C. fulvum infection. CONCLUSION: Our results provide new insight into the Cf-mediated mechanism of resistance to C. fulvum, especially the unique characteristics of Cf-16 tomato in response to this fungus.


Assuntos
Cladosporium/fisiologia , Doenças das Plantas/genética , Proteínas de Plantas/genética , Solanum lycopersicum/genética , Perfilação da Expressão Gênica , Solanum lycopersicum/microbiologia , Doenças das Plantas/microbiologia , Proteínas de Plantas/metabolismo
13.
Ren Fail ; 41(1): 175-182, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30942135

RESUMO

OBJECTIVE: To detect the combination protective effect of bone marrow mesenchymal stem cells (BMSCs) and Klotho gene on the renal ischemia-reperfusion injury (RIRI). METHODS: BMSCs isolated from rats were transfected with Klotho gene to form BMSCKl. We injected BMSCKl to allogenic rat RIRI model. After 24 h and 72 h, we detected the serum creatinine (SCr), malondialdehyde (MDA), and superoxide dismutase (SOD) in renal tissue, Hematoxylin-eosin (HE) staining, and TUNEL of renal pathology. The expression of FoxO1 and p-FoxO1 in post-hypoxia tubular epithelial cells of normal rat kidney (NRK-52E) were detected by Western blot after cocultured with BMSCKl. RESULTS: Comparing with BMSCCon group, Rats in BMSCKl group had lower SCr and MDA but higher SOD. Both HE and TUNEL score of renal tissue in BMSCKl group were lower than that of BMSCCon group. Western blot indicated that FoxO1 was upregulated, while p-FoxO1 was downregulated in post-hypoxia NRK-52E cells. CONCLUSIONS: BMSCs transfected with Klotho gene can further ameliorate RIRI. The possible mechanism may be attributed to the upregulation of SOD in NRK-52E caused by Klotho-FoxO1 axis.


Assuntos
Glucuronidase/metabolismo , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , Traumatismo por Reperfusão/terapia , Animais , Engenharia Celular/métodos , Linhagem Celular , Técnicas de Cocultura , Modelos Animais de Doenças , Regulação para Baixo , Glucuronidase/genética , Humanos , Rim/irrigação sanguínea , Rim/metabolismo , Rim/patologia , Proteínas Klotho , Masculino , Proteínas do Tecido Nervoso/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/patologia , Transdução de Sinais , Superóxido Dismutase/metabolismo , Transfecção , Resultado do Tratamento , Regulação para Cima
14.
Mol Med Rep ; 19(4): 2707-2715, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30720096

RESUMO

Large­scale genomics studies have identified recurrently mutated genes in the ETS gene family, including fusions and copy number variations (CNVs), which are involved in the development of prostate adenocarcinoma (PRAD). However, the aetiology of PRAD remains to be fully elucidated. In the present study, 333 driver genes were identified using four computational tools: OncodriveFM, OncodriveCLUST, iCAGES and DrGaP. In addition, 32 driver pathways were identified using DrGaP. SPOP, TP53, SPTA1, AHNAK, HMCN1, ATM, FOXA1, CSMD3, LRP1B and FREM2 were the 10 most recurrently mutated genes in PRAD. ITGAL, TAGAP, SIGLEC10, RAC2 and ITGA4 were the five hub genes in the yellow module that were associated with the number of positive lymph nodes. Hierarchical clustering analysis of the 20 driver genes with the most frequent CNVs revealed three clusters of patients with PRAD. Cluster 3 tumours exhibited significantly higher numbers of positive lymph nodes, higher Gleason scores, more advanced cancer stages and poorer prognosis than cluster 1 and 2 tumours. A total of 48 genes were significantly associated with the number of positive lymph nodes, Gleason scores and pathologic stage in patients with PRAD. The identified set of cancer genes and pathways sheds light on the tumorigenesis of PRAD and creates avenues for the development of prognostic biomarkers and driver gene­targeted therapies in PRAD.


Assuntos
Adenocarcinoma/genética , Biomarcadores Tumorais , Biologia Computacional , Oncogenes , Neoplasias da Próstata/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Biologia Computacional/métodos , Variações do Número de Cópias de DNA , Perfilação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Masculino , Anotação de Sequência Molecular , Mutação , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Reprodutibilidade dos Testes
15.
Zhonghua Nan Ke Xue ; 23(3): 256-261, 2017 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-29706048

RESUMO

OBJECTIVE: To systematically analyze the correlation between psoriasis and erectile dysfunction (ED). METHODS: We searched the Cochrane Library, EMbase, PubMed, OVID, Medline, VIP, WanFang, China National Knowledge Infrastructure (CNKI), and Chinese Biomedical Literature Database (CBM via SinoMed) for the published literature about the relationship between psoriasis and ED up to June 2016. According to inclusion and exclusion criteria, two researchers respectively extracted the relevant data and made a meta-analysis on the correlation of psoriasis with ED and IIEF-5 scores using the Review Manager 5.3 software. RESULTS: A total of 6 studies were included in this analysis. The analysis with the fixed-effects model revealed a significant correlation between psoriasis and ED (OR = 1.92, 95% CI: 1.53-2.40, P <0.01), and that on 3 of the studies with the random-effects model showed that the IIEF-5 scores were significantly lower in psoriasis patients than in non-psoriasis males (MD = -3.11, 95% CI: -4.85--1.37, P <0.01). CONCLUSIONS: There is a certain correlation between psoriasis and ED. Psoriasis patients may have a higher incidence of ED though it is to be further confirmed by more higher-quality studies.


Assuntos
Disfunção Erétil/complicações , Psoríase/complicações , Disfunção Erétil/epidemiologia , Humanos , Masculino , Psoríase/epidemiologia
16.
Angew Chem Int Ed Engl ; 54(49): 14815-8, 2015 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-26473615

RESUMO

The creation of three consecutive chiral carbon centers in one step is achieved using Cu-catalyzed asymmetric silylative cyclization of cyclohexadienone-tethered allenes. Through regioselective ß-silylation of the allene and subsequent enantioselective 1,4-addition to cyclohexadienone, this tandem reaction could afford cis-hydrobenzofuran, cis-hydroindole, and cis-hydroindene frameworks with excellent yields (80-98%) and enantioselectivities (94-98% ee) bearing vinylsilane and enone substructures. Meanwhile, this mild transformation is generally compatible with a wide range of functional groups, which allows further conversion of the bicyclic products to bridged and tricyclic ring structures.

17.
Int Urol Nephrol ; 47(9): 1577-85, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26246037

RESUMO

PURPOSE: To investigate any association between post-transplantation anemia (PTA) and clinical outcomes following living donor kidney transplantation. METHODS: We retrospectively evaluated 887 patients who received living donor kidney transplantations at our medical center between January 2006 and December 2012 to evaluate whether PTA, defined as serum hemoglobin (Hb) levels of <130 g/l in men and <120 g/l in women, at 12 months is associated with post-transplant outcomes, including graft function, death-censored graft survival, or patient survival. RESULTS: The prevalence of PTA at 1, 3, 6, and 12 months was 84.3, 39.5, 26.2, and 21.6 %, respectively. Donor age [hazard ratio (HR), 1.03; 95 % confidence interval (CI) 1.01-1.05] and acute rejection (HR 2.13; 95 % CI 1.28-3.54) were found to be independent risk factors for PTA at 12 months. Recipient age (HR 0.98; 95 % CI 0.95-1.00), pre-transplantation Hb levels (HR 0.99; 95 % CI 0.98-1.00), and estimated glomerular filtration rates (eGFRs) at 12 months (HR 0.96; 95 % CI 0.94-0.97) were found to confer slight protection against PTA at 12 months. PTA at 12 months was associated with increased graft loss (HR 1.046; 95 % CI 1.045-1.046). For each increase in anemia degree, there was a 2.77-fold greater risk of graft loss (HR 2.77; 95 % CI 1.50-5.13). When stratified according to eGFR, PTA was found to be a predictor of graft loss in patients with an eGFR of <60 ml/min/1.73 m(2) (HR 4.57; 95 % CI 1.98-10.56) but not in patients with an eGFR of >60 ml/min/1.73 m(2) (HR 1.89; 95 % CI 0.13-27.78). PTA was not found to be a predictor of patient survival. CONCLUSIONS: Anemia is common after kidney transplantation, and its prevalence declines with time after transplantation. Presence of anemia at 12 months post-transplant was an independent predictor of graft loss, with higher risk of graft loss in patients with anemia and poorer kidney functions.


Assuntos
Anemia/epidemiologia , Sobrevivência de Enxerto , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Doadores Vivos , Complicações Pós-Operatórias , Medição de Risco/métodos , Adulto , Anemia/etiologia , China/epidemiologia , Feminino , Seguimentos , Humanos , Falência Renal Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Fatores de Tempo
18.
Chin Med J (Engl) ; 127(22): 3970-4, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25421199

RESUMO

BACKGROUND: Bladder cancer is widely known as the most common malignant tumor in the urinary tract, with 75%-85% of patients suffering from nonmuscle invasive bladder cancer (NMIBC). However, the optimal dose of Bacillus Calmette-Guérin (BCG) remains controversial. The aim of this study was to compare the therapeutic efficacy of full dose (FD) with the reduced dose (RD) of BCG. METHODS: Randomized controlled trials (RCTs) were selected through the Cochrane Library, PubMed and Embase and were supplemented by hand searching of bibliographies. The end points include overall survival rate, recurrence rate, progression rate and side effects. RESULTS: Five RCTs that included a total of 1 473 patients (727 in the reduced dose group vs 746 in the full dose group), with a median follow-up period from 33.5 month to 7.1 year. Disease in 80 of 687 (11.6%) patients assigned to the RD group progress to the muscular layer or distant metastasis, compared with 81 of 698 (11.6%) patients assigned to the FD group (RR = 1.02; 95% CI, 0.77-1.36; P = 0.89). The incidence of recurrence at three year was reported in all five studies to be 41.1% (299 of 727) and 36.1% (269 of 746) in the RD and FD groups, respectively (RR = 1.13; 95% CI, 1.00-1.29; P = 0.05). The 5-year survival rate was 75.9% (502 of 662) in the RD group, and 75.8% (510 of 673) in the FD group. In the RD group 41 of 655 (6.3%) patients and 56 of 663 (8.7%) patients in the FD group did not complete the treatment due to systemic or local side effects (RR = 0.75; 95% CI, 0.51-1.10; P = 0.14) CONCLUSIONS: In general, the results of our study demonstrate a trend towards a reduction of the toxicity in reduced dose group without affecting the efficacy of treatment when compared with full dose. More trials with large sample size are still necessary to explore the prognosis of the patients with high risk of tumor in different dose group.


Assuntos
Vacina BCG/uso terapêutico , Neoplasias da Bexiga Urinária/prevenção & controle , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Int Urol Nephrol ; 46(11): 2143-5, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25099526

RESUMO

OBJECTIVE: To investigate the incidence and causes of urethral stricture after kidney transplantation, as well as analyze its diagnosis, treatment and prevention. METHODS: Clinical data of patients who developed urethral stricture after living-donor kidney transplantation in our center between January 2007 and June 2012 were retrospectively analyzed. RESULTS: Urethral stricture occurred in 8 of the 677 eligible kidney recipients (1.18 %) during the study period; the complication occurred at a mean of 4.4 months (range 2-7 months) after transplantation. Cystoscope-related iatrogenic injury and urinary tract infection seemed to be the most likely causes. In addition to frequency and dysuria, three patients had hydronephrosis and four had elevated serum creatinine levels. Urethrography showed that the urethral stricture was anterior in two patients and posterior in the remaining six. Two patients were treated by urethral dilation, four by internal urethrotomy and two by urethra reconstruction surgery. All patients urinated readily after treatment and four patients with impaired renal function recovered. CONCLUSION: Urethral strictures after kidney transplantation are rare, and they can be safely and effectively treated by urethral dilation, internal urethrotomy or urethra reconstruction. Avoiding iatrogenic injury and shortening catheterization time may help reduce the risk of this complication.


Assuntos
Transplante de Rim/efeitos adversos , Procedimentos de Cirurgia Plástica/métodos , Complicações Pós-Operatórias , Estreitamento Uretral/cirurgia , Procedimentos Cirúrgicos Urológicos/métodos , Adulto , Feminino , Seguimentos , Humanos , Falência Renal Crônica/cirurgia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Estreitamento Uretral/diagnóstico , Estreitamento Uretral/etiologia , Urografia , Adulto Jovem
20.
Urology ; 77(4): 836-41, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21146861

RESUMO

OBJECTIVES: To examine the clinical characteristics, treatment, and survival of adult patients with renal sarcoma treated at our institution during the past 2 decades. METHODS: A retrospective review of the demographic, presentation, treatment, and outcome data for 41 adult patients with renal sarcoma treated at our institution from January 1989 to December 2009 was performed. The clinicopathologic parameters were analyzed to determine their effect on survival. RESULTS: Of the 41 patients, 18 were women and 23 were men. Their median age was 42 years (range 19-76). The median tumor size was 13 cm (range 4-35); 29 cases (70.7%) were high grade. The predominant histologic subtype was leiomyosarcoma (39.0%). At diagnosis, 6 patients (14.6%) had metastatic disease. Surgical resection was performed in 34 patients (82.9%), with negative margins in 22 (53.7%). After a median follow-up of 24 months (range 3-80), 3 patients (8.1%) had survived disease free, 11 (29.7%) were alive with disease, and 23 (62.2%) had died of disease. The overall 1-, 3-, and 5-year survival rate was 86.3%, 40.7%, and 14.5%, respectively, and the median survival was 28 months. The median survival after recurrence was 10 months (range 4-24) and that after metastasis 8 months (range 0-22). On univariate analyses, nonmetastatic disease (P = .001) and surgical resection (P = .000) were predictive of a favorable outcome. On multivariate analyses, surgical resection was the only independent predictor of survival (hazard ratio 35.629, P = .022). CONCLUSIONS: Adult renal sarcoma accounts for 0.8% of renal cancer cases and has a poor prognosis. Early diagnosis and surgical resection offer patients the best chance of survival.


Assuntos
Neoplasias Renais/mortalidade , Sarcoma/mortalidade , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Leiomiossarcoma/mortalidade , Leiomiossarcoma/patologia , Leiomiossarcoma/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/epidemiologia , Prognóstico , Estudos Retrospectivos , Sarcoma/patologia , Sarcoma/cirurgia
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