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1.
Pediatr Pulmonol ; 55(1): 68-75, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31596059

RESUMO

AIM: This study aimed to explore the link between neutrophil extracellular traps (NETs) and childhood asthma, to investigate the ability of nitric oxide (NO) to induce NETs in asthmatic children and find inhibitors to reduce NETs in the NO synthesis pathway. METHODS: A total of 49 children with mild persistent asthma were included in the study and 20 healthy children's blood samples were collected as healthy controls. Children with asthma were divided into symptomatic and asymptomatic groups according to the presence or absence of symptoms on the day of blood collection. Neutrophils in peripheral blood were isolated and plasma was preserved. NO donor (sodium nitroferricyanide(III) dehydrate [SNP]) could provide NO and proved by a fluorescent probe. A PicoGreen Kit was used to detect the NETs quantificationally. Fluorescence microscopy prepared to observe the main structures of NETs. We measured NETs components (extracellular free double-stranded DNA [dsDNA]) in healthy, symptomatic and asymptomatic groups' plasma samples, and we compared the ability of SNP with phosphate-buffered saline, lipopolysaccharides (LPS), and phorbol 12-myristate 13-acetate (PMA) to induce NETs. NO synthase (NOS) inhibitors were added to see the impact on NETs formation. RESULTS: Plasma was obtained from all blood samples of 69 children. The neutrophils of 40 asthmatic and 20 healthy children were successfully obtained, the recovery rate was over 95%, and the cell activity was over 80%. There was higher extracellular free dsDNA in the plasma of symptomatic group (n = 27) than asymptomatic group (n = 22) and healthy group (n = 20; P < .05). Studies on neutrophils from 40 children with asthma found that NO can be produced by adding SNP, PMA, and LPS. SNP could induce NETs with dose- and time-dependent. PMA (160 nM) had the strongest ability to induce NETs, LPS (200 ng/mL) followed, SNP (200 µM) was the weakest (P < .05), and the amount of NETs in the asthma group was significantly higher than that in the healthy group (P < .05). NOS inhibitors had the same blocking capacity for PMA- and LPS-induced NETs (P > .05), while NG-nitro- l-arginine methyl ester (500 µM) had the strongest inhibitory effect on SNP induction with time-dependent (P < .05). Inducible NOS was found in the NETs structure. CONCLUSION: Children with asthma had higher levels of NETs in peripheral blood, especially when they had asthma symptoms. We verified the ability of NO to induce NETs, and found neutrophils from asthmatic children can produce more NETs in vitro. NOS inhibitors blocked this process may provide new therapeutic targets for childhood asthma.

2.
Front Public Health ; 7: 344, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31824910

RESUMO

Background: The growth rate of centenarians was unusually rapid in recent decades, ushering in an era of longevity. This study aims to explore the difference between centenarians and non-centenarians using quantitative research, and to scientifically guide residents to develop the correct lifestyle and health care ways. Methods: From October 2013 to August 2017. A cross-sectional survey was conducted on 271 centenarians and 570 non-centenarians by using a questionnaire to assess longevity and health issues which was developed for the needs of the study, who came from 29 counties and districts in 11 cities of Zhejiang province, China. Two hundred and fifty-five valid questionnaires were returned, with an effective response rate of 94.1%. Meanwhile, data of 526 non-centenarians from Zhejiang province was collected as a control group, with an effective response rate of 92.3%. Results: The prevalence rates of tumor, stomach and duodenal ulcer, diabetes, bronchial asthma, and chronic obstructive pulmonary disease, tuberculosis among centenarians were all lower than those among non-centenarians. The oral health of centenarians is better than that of non-centenarians. The consumption of coarse cereals, pasta, other staple foods and fruits among centenarians was higher than that of non-centenarians. The percentage of centenarians who smoke or engage in recreational activities every day was lower than that of non-centenarians. Conclusions: We should give full play to the role of preventive medicine and health management to safeguard the health of residents. Pay attention to oral health, and develop the good habit of loving teeth. The diet should be rich and varied, and increase the intake of grains and fruits. Give up smoking, limit alcohol, spirit-preserving with calming, follow the law of scientific regimen.

3.
Histopathology ; 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31872452

RESUMO

BACKGROUND: Renal cell carcinomas are relatively rare in children and young adults. While well characterized in adults, the morphologic and molecular characterization of these tumors in young patients is relatively lacking. OBJECTIVE: To explore the spectrum of renal cell carcinoma (RCC) subtypes in children and young adults and to determine their clinical-pathological, immunohistochemical and molecular characteristics, by evaluating a large retrospective cohort of renal cell carcinoma patients 30 years of age or younger. RESULTS: Sixty-eight cases with confirmed diagnosis of renal cell carcinoma at 30 years of age or younger were identified at our institution. Clear cell carcinoma accounted for the most common subtype seen in this age group. Translocation renal cell carcinoma and rare familial syndrome subtypes such as succinate dehydrogenase deficient renal cell carcinoma and Tuberous Sclerosis Complex- associated renal cell carcinoma were found relatively more frequently in this cohort. Despite applying the 2016 WHO classification criteria, a high proportion of the tumors in our series remained unclassified. CONCLUSIONS: Our results suggest that renal cell carcinoma in children and young adults is a relatively rare disease that shares many histologic similarities to renal cell carcinoma occurring in adults and yet demonstrate some unique clinical-pathological differences. MiT family translocation RCC and rare familial syndrome subtypes are relatively more frequent in the pediatric and adolescent age groups than in adults. Clear cell RCC still accounted for the most common subtype seen in this age group. MiT family translocation RCC patients presented with advanced stage disease and had poor clinical outcomes. The large and heterogeneous subgroup of unclassified renal cell carcinoma contains phenotypically distinct tumors with further potential for future subcategories in the renal cell carcinoma classification.

4.
Acta Pharmacol Sin ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31705124

RESUMO

Stem cell therapy represents the potential alternative effective strategy for some diseases that lack effective treatment currently. Correspondingly, it is crucial to establish high-sensitive and reliable quantification assay for tracing exogenous cell migration. In the present study, we first used both bioluminescence imaging (BLI) indirect labeling (human norepinephrine transporter-luciferase reporter system) and 89zirconium (89Zr)-hNSCs direct labeling combined with positron emission tomography/computer tomography (PET/CT) system for tracking human neural stem cells (hNSCs) migration into the brain via nasal administration in preclinical study. But the above two methods failed to give the biodistribution profile due to their low sensitivity. Considering its superior sensitivity and absolute quantitation capability, we developed and validated the droplet digital PCR (ddPCR) targeting species-specific gene in frozen and paraffin sections, slices, and whole blood with the sensitivity of 100-200 hNSCs. Accurate and high throughput quantification could be performed using ddPCR with the coefficient of variation (CVs) of lower quality control (LQC) below 30%. In combination with immunohistochemistry and ddPCR, we confirmed the migration of hNSCs into the brain via nasal administration, which supported the efficacy of hNSCs in MPTP-treated mice, an animal model of Parkinson's disease. In conclusion, the present study is the first to report the application of ddPCR in the pharmacokinetics profile description of tracking of hNSCs in preclinical studies.

5.
Bioorg Med Chem ; 27(23): 115153, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31648877

RESUMO

In this study, a series of shikonin derivatives combined with benzoylacrylic had been designed and synthesized, which showed an inhibitory effect on both tubulin and the epidermal growth factor receptor (EGFR). In vitro EGFR and cell growth inhibition assay demonstrated that compound PMMB-317 exhibited the most potent anti-EGFR (IC50 = 22.7 nM) and anti-proliferation activity (IC50 = 4.37 µM) against A549 cell line, which was comparable to that of Afatinib (EGFR, IC50 = 15.4 nM; A549, IC50 = 6.32 µM). Our results on mechanism research suggested that, PMMB-317 could induce the apoptosis of A549 cells in a dose- and time-dependent manner, along with decrease in mitochondrial membrane potential (MMP), production of ROS and alterations in apoptosis-related protein levels. Also, PMMB-317 could arrest cell cycle at G2/M phase to induce cell apoptosis, and inhibit the EGFR activity through blocking the signal transduction downstream of the mitogen-activated protein MAPK pathway and the anti-apoptotic kinase AKT pathway; typically, such results were comparable to those of afatinib. In addition, PMMB-317 could suppress A549 cell migration through the Wnt/ß-catenin signaling pathway in a dose-dependent manner. Additionally, molecular docking simulation revealed that, PMMB-317 could simultaneously combine with EGFR protein (5HG8) and tubulin (1SA0) through various forces. Moreover, 3D-QSAR study was also carried out, which could optimize our compound through the structure-activity relationship analysis. Furthermore, the in vitro and in vivo results had collectively confirmed that PMMB-317 might serve as a promising lead compound to further develop the potential therapeutic anticancer agents.

6.
J Clin Neurosci ; 70: 14-19, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31629608

RESUMO

Cognitive dysfunction and pro-inflammatory effect has been associated with major depressive disorder (MDD), but sex differences have seldom been studied. The study was to determine the sex difference of cognitive dysfunction and pro-inflammatory biomarkers among patients with MDD in Chinese Han population. 104 MDD patients (male n = 37, female n = 67) were included in the study. Their sociodemographic and clinical features, including age, body mass index (BMI), education, smoking, alcohol use, illness characteristics and medicine use were recorded. Montreal Cognitive Assessment (MoCA) was used to assess cognition. And we detected pro-inflammatory biomarkers Interleakin-1ß (IL-1ß), Interleakin-6 (IL-6) and C-reaction protein (CRP) levels by enzyme linked immunosorbent assay. We found that male patients showed higher scores than female in MoCA, and performed better than female patients particularly in visuaspatial, naming, attention, orientation subscale. CRP and IL-1ß levels showed no significant difference between male and female patients in MDD. However, Male's IL-6 level was significantly declined than female, negative closed associated with cognition in MOCA score. These results suggested that the difference in IL-6 could reflect a cognitive difference between male and female in MDD, and IL-6 elevation could represent a state indicator for cognitive ability particular in female MDD patients. And it maybe a biological treatment target in cognition dysfunction of female patients in MDD.


Assuntos
Biomarcadores/sangue , Disfunção Cognitiva/imunologia , Transtorno Depressivo Maior/imunologia , Interleucina-6/sangue , Caracteres Sexuais , Adulto , Grupo com Ancestrais do Continente Asiático , Disfunção Cognitiva/sangue , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/complicações , Feminino , Humanos , Interleucina-6/imunologia , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade
7.
Mod Pathol ; 32(12): 1795-1805, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31300804

RESUMO

Histologically, drug-induced liver injury could be classified into acute hepatitis, chronic hepatitis, acute cholestasis, chronic cholestasis, and cholestatic hepatitis. The correlation between these histologic patterns and long-term clinical outcomes has not been well established. Therefore, we conducted a retrospective cohort study to investigate the association of histologic patterns and long-term clinical outcomes defined as biochemical normalization, persistent abnormal liver biochemistry or death at designated time points. In this study, biochemical classification was determined by R-values; histologic injury pattern was determined by morphological features. Predictive ability of clinical outcomes by these two classifications was assessed using Receiver Operating Characteristic Curves. Logistic regression was performed to identify histologic factors associated with outcomes. Totally, 88 patients with drug-induced liver injury were included for final analysis. Biochemical and histologic classification were consistent in 50 (57%) cases. 53 (60%) cases showed biochemical normalization within 6 months, and a further 11 (13%), 16 (18%), and 6 (7%) cases within 1, 2, and 3 years, respectively. Compared with biochemical classification, histologic injury pattern had better predictive ability for abnormal biochemistry at 6 months (Areas under Receiver Operating Characteristic Curves 0.92 versus 0.60, P < 0.001) and 1 year (Areas under Receiver Operating Characteristic Curves 0.94 versus 0.69, P < 0.001). Interlobular bile duct loss in >25% portal areas was independently associated with abnormal biochemistry at 6 months, 1 year, and 2 years. In conclusion, histologic injury pattern is better correlated with clinical outcome at 6 months and 1 year than biochemical classification. Moderate bile duct loss is an important histologic feature associated with persistent biochemical abnormality at 6 months, 1 year, and 2 years.

8.
World J Clin Cases ; 7(10): 1230-1233, 2019 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-31183357

RESUMO

BACKGROUND: It is rare to find fish bones completely embedded in the wall of the esophagus with endoscopic findings similar to those of submucosal tumors. Most of the patients had the foreign body removed by thoracotomy or thoracoscopy in the past, which resulted in great trauma. CASE SUMMARY: We report a 58-year-old woman who experienced dysphagia for 6 d after eating fish. Cervical computed tomography (CT) and endoscopic ultrasonography (EUS) indicated a fish bone completely embedded in the wall of the esophagus with endoscopic findings similar to those of submucosal tumors. The results of CT reconstruction and EUS suggested that the fish bone was parallel to the longitudinal axis of the esophagus. We performed a longitudinal mucosal incision from the highest point of the uplift by using an Olympus dual knife to find the fish bone. Unfortunately, no fish bone was found, so we extended the incision and endoscopic submucosal dissection (ESD) technique was used to detect and remove the fish bone entirety. CONCLUSION: The extraction of fish bone via ESD immediately after the injection of methylene blue into the submucous membrane under EUS guidance to obtain accurate localization of the foreign body may be the best treatment for such patients.

9.
ACS Appl Mater Interfaces ; 11(23): 20678-20688, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-31081332

RESUMO

Responsive nanocarriers with biocompatibility and precise drug releasing capability have emerged as a prospective candidate for anticancer treatment. However, the challenges imposed by the complicated preparation process and limited loading capacities have seriously impeded the development of novel multifunctional drug delivery systems. Here, we developed a novel and dual-responsive nanocarrier based on a nanoscale ZIF-8 core and an organosilica shell containing disulfide bridges in its frameworks through a facile and efficient strategy. The prepared ZIF-8@DOX@organosilica nanoparticles (ZDOS NPs) exhibited a well-defined structure and excellent doxorubicin (DOX) loading capability (41.2%) with pH and redox dual-sensitive release properties. The degradation of the organosilica shell was observed after 12 h incubation with a 10 mM reducing agent. Confocal imaging and flow cytometry analysis further proved that the nanocarriers can efficiently enter cells and complete intracellular DOX release under the low pH and high glutathione concentrations, which resulted in an enhanced cytotoxicity of DOX for cancer cells. Meanwhile, subcellular localization experiments revealed that the ZDOS NPs entered cells mainly by endocytosis and then escaped from lysosomes into the cytosol. Moreover, in vivo assays also demonstrated that the ZDOS NPs exhibited negligible systemic toxicity and significantly enhanced anticancer efficiencies compared with free DOX. In summary, our prepared pH and redox dual-responsive nanocarriers provide a potential platform for controlled release and cancer treatment.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Estruturas Metalorgânicas/química , Nanopartículas/química , Dióxido de Silício/química , Neoplasias do Colo do Útero/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Doxorrubicina/química , Doxorrubicina/uso terapêutico , Liberação Controlada de Fármacos , Feminino , Citometria de Fluxo , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Transmissão , Oxirredução , Espécies Reativas de Oxigênio/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier
10.
Prog Orthod ; 20(1): 20, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31111270

RESUMO

BACKGROUND: To determine the discrepancy of crown-root morphology of central incisors among different types of skeletal malocclusion using cone-beam computed tomography (CBCT) and to provide guidance for proper torque expression of anterior teeth and prevention of alveolar fenestration and dehiscence. METHODS: In this retrospective study, a total of 108 CBCT images were obtained (ranging from 18.0 to 30.0 years, mean age 25.8 years). Patients were grouped according to routine sagittal and vertical skeletal malocclusion classification criteria. The patients in sagittal groups were all average vertical patterns, with Class I comprised 24 patients-14 females and 10 males; Class II comprised 20 patients-13 females and 7 males; and Class III comprised 22 subjects-13 females and 9 males. The patients in vertical groups were all skeletal Class I malocclusions, with low angle comprised 21 patients-12 females and 9 males; average angle comprised 24 patients; and high angle comprised 21 patients-11 females and 10 males. All the CBCT data were imported into Invivo 5.4 software to obtain a middle labio-lingual section of right central incisors. Auto CAD 2007 software was applied to measure the crown-root angulation (Collum angle), and the angle formed by a tangent to the central of the labial surface of the crown and the long axis of the crown (labial surface angle). One-way analysis of variance (ANOVA) and Scheffe's test were used for statistical comparisons at the P < 0.05 level, and the Pearson correlation analysis was applied to investigate the association between the two measurements. RESULTS: The values of Collum angle and labial surface angle in maxillary incisor of Class II and mandibular incisor of Class III were significantly greater than other types of sagittal skeletal malocclusions (P < 0.05); no significant difference was detected among vertical skeletal malocclusions. Notably, there was also a significant positive correlation between the two measurements. CONCLUSIONS: The maxillary incisor in patients with sagittal skeletal Class II malocclusion and mandibular incisor with Class III malocclusion present remarkable crown-root angulation and correspondingly considerable labial surface curvature. Equivalent deviation during bracket bonding may cause greater torque expression error and increase the risk of alveolar fenestration and dehiscence.


Assuntos
Má Oclusão de Angle Classe III , Má Oclusão , Adulto , Tomografia Computadorizada de Feixe Cônico , Coroas , Feminino , Humanos , Incisivo , Masculino , Maxila , Estudos Retrospectivos
11.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(4): 354-358, 2019 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-31014428

RESUMO

OBJECTIVE: To summarize and analyze the etiology, clinical manifestations and imaging features of children with cerebral infarction. METHODS: A retrospective analysis was performed for the clinical data of 54 children with cerebral infarction, including etiology, clinical manifestations, distribution of infarcts, type of infarcts and clinical outcome. RESULTS: Of the 54 children, 93% had a clear cause, among whom 46% had the coexistence of multiple factors, and the top three causes were infection (54%), vascular disease (40%) and trauma (26%). Major clinical manifestations included limb paralysis (85%), pyrexia (20%), disturbance of consciousness (19%) and convulsion (17%). As for the location of infarcts, 80% of the infarcts were located in the cerebral cortex and 52% in the basal ganglia. Major types of infarcts were small-area infarcts (74%) and multifocal infarcts (56%). Viral encephalitis was the most common cause of cerebral infarction caused by infection, with the cerebral cortex as the most common location of infarcts (21/23, 91%) and multiple infarcts as the most common type of infarcts (13/23, 57%). Among the 12 children with cerebral infarction caused by nonspecific endarteritis, 10 (83%) had infarcts located in the basal ganglia and only one child had multiple infarcts. Among the five children with cerebral infarction caused by moyamoya disease, four children (80%) had infarcts located in the cerebral cortex, and large-area infarction (4/5, 80%) and multifocal infarction (4/5, 80%) were the major types of infarcts. Among the children with traumatic cerebral infarcts, 92% had infarcts located in the basal ganglia, and small-area infarcts (92%) and single infarcts (85%) were the major types of infarcts. Among the 46 children with limb paralysis, 34 (74%) had infarcts located in the basal ganglia; 50% of the children with disturbance of consciousness had infarcts located in the basal ganglia. Subcortical infarcts were observed in all six children with epilepsy. Seventy-five percent of the infarcts located in the cerebral cortex and 87% of the infarcts located in the basal ganglia had a good prognosis. Among the two children with cerebral infarcts located in the brainstem, one had the sequela of hemiplegia and the other had the sequela of cognitive impairment. Eighty-eight percent of the children with cerebral infarction caused by infection and 82% of the children with traumatic cerebral infarction tended to have a good prognosis, and 83% of the children with cerebral infarction caused by nonspecific endarteritis had good prognosis. Recurrence was observed in all three children with cerebral infarction caused by vascular malformations. Of the five children with cerebral infarction caused by moyamoya disease, one child died and four children survived with the sequela of localized brain atrophy, among whom one child also had the sequela of epilepsy. CONCLUSIONS: Infection, vascular disease and trauma are the most common causes of cerebral infarction in children, and limb paralysis is the most common clinical manifestation. Cerebral cortex is the most common infarct site, and small-area infarcts and multifocal infarcts are the most common types of infarcts, which tend to have a better prognosis.


Assuntos
Infarto Cerebral , Gânglios da Base , Córtex Cerebral , Criança , Humanos , Imagem por Ressonância Magnética , Recidiva , Estudos Retrospectivos
12.
J Int Med Res ; 47(4): 1802-1809, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30819006

RESUMO

Gastric varices are found in approximately 20% of patients with portal hypertension. Endoscopic procedures involving the injection of cyanoacrylate (CYA) have proven to be the therapies of choice for primary treatment of gastric varices and have resulted in higher hemostasis rates and lower recurrent bleeding rates compared with band ligation and sclerotherapy. Nevertheless, serious adverse events associated with CYA injection, including glue embolization, have been reported in numerous articles and have occasionally led to fatal adverse events. Gastric fundal varices with abnormal shunts are higher-risk than those without abnormal shunts, and their treatment is more challenging. Endoscopic ultrasound (EUS)-guided puncture is an important technique in the field of digestive endoscopy. EUS has advantages that include improved therapeutic targeting, enhanced variceal detection, the ability to confirm varix obliteration with Doppler examination, and the ability to perform accurate observations of gastric varices that are not affected by blood in the stomach. The coils currently used for intravascular embolization can be precisely delivered into a varix through fine-needle puncture under EUS guidance, and this technique has provided a new approach for varix obliteration. We herein describe two patients with severe gastric fundal varices who were treated with EUS-guided coil injection and CYA embolization.


Assuntos
Cianoacrilatos/administração & dosagem , Endossonografia/métodos , Varizes Esofágicas e Gástricas/terapia , Fundo Gástrico/cirurgia , Hemorragia Gastrointestinal/terapia , Cirurgia Assistida por Computador/métodos , Varizes Esofágicas e Gástricas/diagnóstico por imagem , Feminino , Fundo Gástrico/diagnóstico por imagem , Hemorragia Gastrointestinal/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
13.
Bioorg Med Chem ; 27(8): 1509-1516, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30846404

RESUMO

A series of rhodanine derivatives RB1-RB23 were synthesized through a two-round screening. Their Mycobacterial tuberculosis (Mtb) InhA inhibitory activity and Mtb growth blocking capability were evaluated. The most potent hit compound RB23 indicated comparable InhA inhibiton (IC50 = 2.55 µM) with the positive control Triclosan (IC50 = 6.14 µM) and Isoniazid (IC50 = 8.29 µM). Its improved growth-blocking effect on Mtb and low toxicity were attractive for further development. The docking simulation revealed the possible binding pattern of this series and picked the key interacted residues as Ser20, Phe149, Lys165 and Thr196. The 3D-QSAR model visualized the SAR discussion and hinted new information. Modifying the surroundings near rhodanine moiety might be promising attempts in later investigations.

15.
Anaerobe ; 56: 116-123, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30849459

RESUMO

Clostridioides difficile is a colonizer of the human gut; asymptomatic colonization has been reported to be more common in infants and is highly variable across regions even with no symptoms of diarrhea or death. Antibiotic treatment strategies might increase the antibiotic resistance of C. difficile. We performed a one-point study involving 1098 healthy infants (0-36 months) to address the deficiency of reports on C. difficile colonization in Chinese community infants. The C. difficile colonization rate was 22.8% (250/1098), and more than half of the strains (55.2%) were toxigenic isolates. Among the 138 toxigenic isolates, 111 were of the A+B+CDT- genotype, 26 strains were A-B+CDT-, and one strain was A+B+CDT+. Fifteen different PCR ribotypes were found among the 250 isolates, and PCR-ribotype HB03 appeared to be dominant type, accounting for 19.6% (49/250). High levels of resistance to antimicrobial agents were observed. Our study showed that age and hospitalization before stool collection were positively correlated with the C. difficile colonization rate, whereas the delivery term was negatively related to the colonization rate. Particular attention should be paid to the increasing resistance of C. difficile to rifamycin.


Assuntos
Portador Sadio/epidemiologia , Infecções por Clostridium/epidemiologia , Clostridium difficile/isolamento & purificação , Grupo com Ancestrais do Continente Asiático , Toxinas Bacterianas/genética , Portador Sadio/microbiologia , China/epidemiologia , Infecções por Clostridium/microbiologia , Genótipo , Voluntários Saudáveis , Humanos , Lactente , Epidemiologia Molecular , Reação em Cadeia da Polimerase , Prevalência , Ribotipagem
16.
Int J Neuropsychopharmacol ; 22(1): 57-70, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30407508

RESUMO

Background: Hyperhomocysteinemia is an independent risk factor for dementia, including Alzheimer's disease. Lowering homocysteine levels with folic acid treatment with or without vitamin B12 has shown few clinical benefits on cognition. Methods: To verify the effect of emodin, a naturally active compound from Rheum officinale, on hyperhomocysteinemia-induced dementia, rats were treated with homocysteine injection (HCY, 400 µg/kg/d, 2 weeks) via vena caudalis. Afterwards, HCY rats with cognitive deficits were administered intragastric emodin at different concentrations for 2 weeks: 0 (HCY-E0), 20 (HCY-E20), 40 (HCY-E40), and 80 mg/kg/d (HCY-E80). Results: ß-Amyloid overproduction, tau hyperphosphorylation, and losses of neuron and synaptic proteins were detected in the hippocampi of HCY-E0 rats with cognitive deficits. HCY-E40 and HCY-E80 rats had better behavioral performance. Although it did not reduce the plasma homocysteine level, emodin (especially 80 mg/kg/d) reduced the levels of ß-amyloid and tau phosphorylation, decreased the levels of ß-site amyloid precursor protein-cleaving enzyme 1, and improved the activity of protein phosphatase 2A. In the hippocampi of HCY-E40 and HCY-E80 rats, the neuron numbers, levels of synaptic proteins, and phosphorylation of the cAMP responsive element-binding protein at Ser133 were increased. In addition, depressed microglial activation and reduced levels of 5-lipoxygenase, interleukin-6, and tumor necrosis factor α were also observed. Lastly, hyperhomocysteinemia-induced microangiopathic alterations, oxidative stress, and elevated DNA methyltransferases 1 and 3ß were rescued by emodin. Conclusions: Emodin represents a novel potential candidate agent for hyperhomocysteinemia-induced dementia and Alzheimer's disease-like features.


Assuntos
Demência/tratamento farmacológico , Demência/etiologia , Emodina/farmacologia , Hiper-Homocisteinemia/complicações , Hiper-Homocisteinemia/tratamento farmacológico , Nootrópicos/farmacologia , Peptídeos beta-Amiloides/metabolismo , Animais , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/metabolismo , Transtornos Cognitivos/patologia , Metilação de DNA/efeitos dos fármacos , Metilação de DNA/fisiologia , Demência/metabolismo , Demência/patologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Hiper-Homocisteinemia/metabolismo , Hiper-Homocisteinemia/patologia , Masculino , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/patologia , Microvasos/efeitos dos fármacos , Microvasos/metabolismo , Microvasos/patologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Distribuição Aleatória , Ratos Sprague-Dawley , Proteínas tau/metabolismo
17.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 49(4): 635-639, 2018 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-30378319

RESUMO

OBJECTIVE: To investigate the effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on the recurrence of non-muscle-invasive bladder cancer (NMIBC). METHODS: Clinical data of 388 patients with NMIBC undergoing transurethral resection of bladder tumor during Jan. 2009 to Dec. 2011 were retrospectively reviewed. Recurrence-free survival was analyzed, and the risk factors of recurrence were explored by Cox multivariate regression analysis. RESULTS: All patients were managed with postoperative intravesical chemotherapy, but 82 of them only received maintenance instillation without immediate instillation. There were 161 patients diagnosed of hypertension, 107 of them were treated with ACEIs or ARBs. No significant differences in age, sex, history of smoking, pathological stage, pathological grade, tumor diameter and post-operation immediate instillation were observed between the patients treated with (drug-use group) or without ACEIs/ARBs (control group). There was also no statistically significant difference among aforementioned indexes after the stratification by hypertension and medication (ACEIs/ARBs). During a median follow up of 60 months, there were 36 and 129 patients found recurrence in drug-use group and control group, respectively. The recurrence free survival times of the patients treated with and without ACEIs/ARBs were (48.43±23.50) and (41.15±23.64) months, respectively (P=0.007). The 5-year recurrence-free survival rate was 66.36% in drug-use group and 54.09% in the controls (P=0.027). Multivariate regression analysis revealed that no ACEIs/ARBs treatment [standardized regression coefficient (ß) =0.174] was independent risk factor of recurrence (P<0.05). The weight of no ACEIs/ARBs treatment was behind to no immediate instillation (ß=0.131), tumor multiplicity (ß=0.128), tumor diameter ≥3 cm (ß=0.193), grade 3 tumor (ß=0.181), and smoking status (ß=0.191). CONCLUSION: Theadministration of ACEIs/ARBs may decrease the recurrence of NMIBC after transurethral resection of bladder tumor.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Recidiva Local de Neoplasia/prevenção & controle , Sistema Renina-Angiotensina , Neoplasias da Bexiga Urinária/tratamento farmacológico , Intervalo Livre de Doença , Humanos , Estudos Retrospectivos
18.
J Vis Exp ; (138)2018 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-30176002

RESUMO

Because precision medicine is highly dependent on the accurate detection of biomarkers, there is an increasing need for standardized and robust technologies that measure RNA biomarkers in situ in clinical specimens. While grind-and-bind assays like RNAseq and quantitative RT-PCR enable highly sensitive gene expression measurements, they also require RNA extraction and thus prevent valuable expression analysis within the morphological tissue context. The in situ hybridization (ISH) assay described here can detect RNA target sequences as short as 50 nucleotides at single-nucleotide resolution and at the single-cell level. This assay is complementary to the previously developed commercial assay and enables sensitive and specific in situ detection of splice variants, short targets, and point mutations within the tissue. In this protocol, probes were designed to target unique exon junctions for two clinically important splice variants, EGFRvIII and METΔ14. The detection of short target sequences was demonstrated by the specific detection of CDR3 sequences of T-cell receptors α and ß in the Jurkat T-cell line. Also shown is the utility of this ISH assay for the distinction of RNA target sequences at single-nucleotide resolution (point mutations) through the visualization of EGFR L858R and KRAS G12A single-nucleotide variations in cell lines using automated staining platforms. In summary, the protocol shows a specialized RNA ISH assay that enables the detection of splice variants, short sequences, and mutations in situ for manual performance and on automated stainers.


Assuntos
Variação Genética/genética , Hibridização In Situ/métodos , Mutação Puntual/genética , RNA/genética , Humanos
19.
Int J Impot Res ; 30(6): 342-351, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30232467

RESUMO

The purpose of the present study was to conduct a meta-analysis of cross-sectional studies assessing the relationship between alcohol consumption and the risk of erectile dysfunction (ED). To identify relevant studies, databases such as Pubmed, Medline, Embase, and the Cochrane Library were searched from the inception of the present study to March 2016. Finally, 24 studies (154,295 patients) were included. We combined a study-specific odds ratio (OR) estimated by using a random effects meta-analysis. The results of our meta-analysis indicated that light to moderate alcohol consumption (<21 drinks/week) was correlated with a decreased risk of erectile dysfunction (OR = 0.71; 95% CI: 0.59-0.86; P = 0.000). However, regular (ever vs. never) and high alcohol consumption (>21 drinks/week) had no significant influence on the prevalence of ED (regular: OR = 0.87; 95% CI: 0.75-1.07; P = 0.062; high: OR = 0.99; 95% CI: 0.80-1.22; P = 0.893). In a dose-response meta-analysis, a non-linear relationship was observed between alcohol consumption and risk of ED (P for non-linearity = 0.0000). In conclusion, moderate intake of alcohol exhibited a beneficial effect on the risk of ED, whereas regular and high consumption did not.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Disfunção Erétil/epidemiologia , Etanol/farmacologia , Ereção Peniana/efeitos dos fármacos , Comportamento Sexual/efeitos dos fármacos , Estudos Transversais , Disfunção Erétil/diagnóstico , Humanos , Masculino , Estudos Observacionais como Assunto , Pênis/irrigação sanguínea , Prevalência , Fatores de Risco
20.
Chem Commun (Camb) ; 54(82): 11598-11601, 2018 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-30264071

RESUMO

We report a novel narrow-band blue emitting phosphor Sr7.92Mg7Si9N22:0.08Eu2+. The crystal structure of Sr8Mg7Si9N22 is composed of corner-sharing and edge-sharing [SiN4] tetrahedra and distorted square-pyramid [MgN5] polyhedra. Under 350 nm excitation, Eu2+ doped Sr8Mg7Si9N22 emits narrow-band blue light with maximum intensity at 450 nm and a fwhm of 38 nm.

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