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1.
World J Urol ; 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31679064

RESUMO

BACKGROUND: The current study aimed to carry out a comprehensive meta-analysis on the existing evidence to quantify and compare the oncological, surgical and functional outcomes following radical prostatectomy between TURP group and Non-TURP group. METHODS: A systematic literature search was conducted using EMBASE, PubMed and Cochrane databases to identify relevant studies published in English up to March 2019. A meta-analysis was conducted using Review Manager. RESULTS: There were 13 studies included in the present study. Our results suggest that TURP group demonstrates a significantly higher positive surgical margin rate, bladder neck reconstruction rate and overall complication rate compared with Non-TURP group (OR = 1.31, 95% CI 1.09-1.58, P = 0.004, I2 = 0%; OR = 14.36, 95% CI 2.93-70.45, P = 0.001, I2 = 81%; OR = 2.63, 95% CI 1.87-3.71, P < 0.00001, I2 = 0%); whereas TURP group demonstrates a significantly lower nerve sparing rate compared with Non-TURP group (OR = 0.30, 95% CI 0.22-0.43, P < 0.00001, I2 = 40%); the operation time, blood loss and 1-year urinary continence rate are same between TURP group and Non-TURP group (MD = 4.25, 95% CI - 0.13 to 8.63, P = 0.06, I2 = 34%; MD = 27.29, 95% CI - 10.31 to 64.90, P = 0.15, I2 = 39%; OR = 0.68, 95% CI 0.43-1.06, P = 0.09, I2 = 0%). CONCLUSION: This meta-analysis demonstrates that Non-TURP group may have a great advantage over TURP group in terms of positive surgical margin rate, bladder neck reconstruction rate, overall complication rate and sparing rate. The operation time, blood loss and 1-year urinary continence rate are comparable between TURP group and Non-TURP group. Therefore, important information should be given to those patients at risk of prostate cancer that TURP procedure may increase perioperative complications in case of a following radical prostatectomy. In the meantime, our meta-analysis found that each of these four subgroups (RARP, LRP, ORP and RARP/ORP) has its own advantages or disadvantages in every pool results. So when radical prostatectomy is performed on patients with TURP history, the appropriate operation method should be selected as per the conditions of patients, doctors and hospitals.

2.
Mod Pathol ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31690781

RESUMO

Inflammatory myofibroblastic tumors arising in infants are rare, poorly investigated and mostly reported as isolated cases or as a part of larger series thus, their clinicopathological and molecular features are essentially unknown. Archival files from two large pediatric institutions and a tumor registry were queried for pediatric inflammatory myofibroblastic tumors. Available material from patients ≤12 months of age was reviewed. Additional immunostains (ALK-1, D240, WT1) and ALK-FISH studies were performed as needed. Targeted anchored multiplex PCR with next-generation sequencing was done in all cases. A total of 12 of 131 infantile cases (mean 5.5 months) were identified (M:F of 2:1). Anatomic locations included intestinal/mesenteric (n = 6), head/neck (n = 3), and viscera (n = 3). Half of tumors showed a hypocellular myxoid pattern, perivascular condensation, and prominent vasculature with vague glomeruloid structures present in four of them. The remaining cases exhibited a more cellular pattern with minimal myxoid component. ALK-1 immunohistochemistry was positive in most cases (11/12) with cytoplasmic-diffuse (n = 6), cytoplasmic-granular (n = 2), and dot-like (n = 3) staining patterns. ALK fusion partners identified in five cases included EML4, TPM4, RANBP2, and a novel KLC1. Three inflammatory myofibroblastic tumors showed fusions with other kinases including TFG-ROS1 and novel FN1-ROS1 and RBPMS-NTRK3 rearrangements. Favorable outcome was documented in most cases (10/11) with available follow-up (median 17 months) while three patients were successfully treated with crizotinib. In summary, infantile inflammatory myofibroblastic tumors are rare and can exhibit paucicellular, extensively myxoid/vascular morphology with peculiar immunophenotype mimicking other mesenchymal or vascular lesions. All tumors harbored kinase fusions involving ALK, ROS1, and NTRK3 including three novel fusion partners (KLC1, FN1, and RBPMS, respectively). A favorable response to crizotinib seen in three cases supports its potential use in infants as seen in older patients. Awareness of these unusual morphologic, immunophenotypic, and molecular features is critical for appropriate diagnosis and optimized targeted therapy.

3.
Medicine (Baltimore) ; 98(45): e17933, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702679

RESUMO

Hemiplegic shoulder pain (HSP), which occurs in most patients with hemiplegia, causes considerable distress and worsens outcomes in rehabilitation. Although they have received the treatments such as anti-inflammatory drugs or physical therapy, many of the individuals remain suffering from shoulder pain 6 months after acute stroke event. In this retrospective study, we evaluated the effectiveness of ultrasound guided subacromial-subdeltoid (SASD) bursa injections with botulinum toxin type A (BoNT/A) compared to steroids for refractory HSP.The data were collected retrospectively by reviewing the patient's medical records and pain questionnaires in our rehabilitation center. In total, 38 patients who received ultrasound guided SASD bursa injection (BoNT/A group, n = 18; corticosteroid group, n = 20) were included. The pain visual analog scale (VAS) score at rest and during arm passive abduction, Fugl-Meyer score of upper limbs (F-M score) were evaluated before, 2, 4, 8, and 12 weeks after injection.Both 2 groups obtained a significant improvement of VAS score at rest or during arms passive abduction compared to baseline score (within group compare, P < .05). There were no significant differences of pain score improvement between two groups at week 2, 4, 8, and 12 after injection either at rest or during passive arm abduction (between 2 groups compare, P > .05). There were also no differences in results of the post treatment F-M score between 2 groups (between 2 groups compare, P > .05). Similarly, during the follow-up period no collateral effects were reported after BoNT/A injection.SASD bursa BoNT/A injection can substantially reduce the pain as corticosteroid in patients with HSP. BoNT/A injection could be a useful strategy for replacing steroids as a treatment for refractory HSP especially in the patients who cannot tolerate the steroids injection.

4.
Parkinsonism Relat Disord ; 68: 85-90, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31689588

RESUMO

INTRODUCTION: Freezing of gait (FOG) contributes to falls in Parkinson's disease (PD), but robust, effective treatments remain elusive. There is evidence indicating that the supplementary motor area (SMA) plays an important role in the pathogenesis of FOG and may therefore be a potential neuromodulation target. The present study explored the clinical efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the SMA on FOG in PD patients. METHODS: A group of 30 PD patients with FOG were enrolled in a randomized, double-blind, sham-controlled trial. Patients were randomly allocated 2:1 to receive ten sessions of either real (N = 20) or sham (N = 10) 10 Hz rTMS over SMA. The patients were assessed at baseline (T0), after the 5th (T1) and 10th (T2) sessions, and then 2 weeks (T3) and 4 weeks (T4) after the last session. The primary clinical outcome was the Freezing of Gait Questionnaire score (FOGQ), with the Movement Disorder Society-Unified Parkinson's Disease Rating Scale motor scores (MDS-UPDRS III) and Timed Up and Go test as secondary clinical outcomes. All the assessments were carried out at the "ON" state. RESULTS: With a four week's follow-up, there were significant interaction effects in the FOGQ (effect of group*time, p = 0.04), MDS-UPDRS III (p = 0.02) and several gait variables (total duration, p < 0.01; cadence, p = 0.04; turn duration, p = 0.01; and turn to sit duration, p = 0.02). Post-hoc analyses revealed a significantly decreased FOGQ score at T2 and T4, and significant improvements of MDS-UPDRS III and gait variables at T1, T2, T3 and T4 in the rTMS group. No significant improvements were found in the sham group. CONCLUSION: High-frequency rTMS over SMA may ultimately serve as an add-on therapy for alleviating FOG in PD patients.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31606549

RESUMO

OBJECTIVES: During surveillance, we found a new type of Vibrio parahaemolyticus that agglutinated with O4 serum but not with K serum, and the recA gene was affected by a large insertion. We named this strain "O4:KUT-recAin". METHODS: The clinical data and stool specimens were collected from acute diarrheal patients in coastal hospitals of China. V. parahaemolyticus was isolated using selective media and identified by MALDI-TOF Microbial Mass Spectrometer. By serum agglutination tests and whole-genome sequencing, we identified a new serotype of V. parahaemolyticus strain. By using a rabbit diarrheal model, we confirmed the pathogenicity of this strain. RESULTS: O4:KUT-recAin strain possessed a new type of K antigen and a 25 043 bp large fragment encoding 20 proteins inserted in housekeeping gene recA. Retrospective analysis found that only one O4:KUT-recAin strain was detected in 563 V. parahaemolyticus strains in 2014; then, the proportion increased rapidly and reached 17.8% (105/590) in 2016 and 31.1% (224/721) in 2017, making O4:KUT-recAin the second dominant serotype following O3:K6. O4:KUT-recAin strains (100%, 14/14) exhibited increased acid resistance and could reproduce in medium at pH= 4.9, while 92.9% (13/14) of the O3:K6 strains could not grow at this pH. O4:KUT-recAin could cause diarrhea and small intestinal tissue lesions in infant rabbits, but its diarrheal (93.1%, 27/29) and mortality (78.6%, 22/28) rates were slightly lower than those of O3:K6 (100% 16/16, 100% 16/16). Based on diarrhea patients, most clinical symptoms and laboratory results were no significant difference in the two groups, except media age, hemoglobin and the red blood cell in the stool. CONCLUSIONS: O4:KUT-recAin had enhanced acid resistance, was capable of causing infectious diarrhea in both rabbits and humans, and has become widespread during a short period of time in China.

6.
Biochem Biophys Res Commun ; 520(2): 486-491, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31606203

RESUMO

PYCR1 exerts an important role in various cancers, but its effect on colorectal cancer (CRC) and the potential mechanism remain to be clarified. In this study, we aimed to explore the effect of PYCR1 on CRC and further explore the special molecular mechanism. The expression of PYCR1 in CRC tissues and cells was analysed by RT-PCR assay. Cell proliferation was explored using an MTT assay. A CoIP assay was performed to determine the binding activity of PYCR1 and STAT3. Western blot was used to measure the protein expression of P-gp, MRP1, E-cadherin and vimentin. The results revealed that PYCR1 is highly expressed in CRC tissues and cells. PYCR1-siRNA inhibited the proliferation, drug resistance and epithelial-mesenchymal transition (EMT) of CRC cells. The CoIP assay result demonstrated that PYCR1 interacts directly with STAT3, and STAT3 overexpression partly reverses the effect of PYCR1 on proliferation, drug resistance and EMT of CRC cells. What is more, si-PYCR1 inhibited STAT3-mediated p38 MAPK and NF-κB signalling pathways. Collectively, it suggests that knockdown of PYCR1 inhibits proliferation, drug resistance and EMT potentially by regulating STAT3-mediated p38 MAPK and NF-κB signalling pathways in CRC cells.

7.
Eur J Med Chem ; 183: 111711, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31585276

RESUMO

Toxoplasma gondii severely threaten the health of immunocompromised patients and pregnant women as this parasite can cause several disease, including brain and eye disease. Current treatment for toxoplasmosis commonly have high cytotoxic side effects on host and require long durations ranging from one week to more than one year. The regiments lack efficacy to eradicate T. gondii tissue cysts to cure chromic infection results in the needs for long treatment and relapsing disease. In addition, there has not been approved drugs for treating the pregnant women infected by T. gondii. Moreover, Toxoplasma vaccine researches face a wide variety of challenges. Developing high efficient and low toxic agents against T. gondii is urgent and important. Over the last decade, tremendous progress have been made in identifying and developing novel compounds for the treatment of toxoplasmosis. This review summarized and discussed recent advances between 2009 and 2019 in exploring effective agents against T. gondii from five aspects of drug discovery.

8.
Aging (Albany NY) ; 11(19): 8463-8473, 2019 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-31586991

RESUMO

PURPOSE: The aim of this study was to determine the impact of analyzing age as a continuous variable on survival outcomes and treatment selection for extranodal nasal-type NK/T-cell lymphoma. RESULTS: The risk of mortality increased with increasing age, without an apparent cutoff point. Patients' age, as a continuous variable, was independently associated with overall survival after adjustment for covariates. Older early-stage patients were more likely to receive radiotherapy only whereas young-adult advanced-stage patients tended to receive non-anthracycline-based chemotherapy. A decreased risk of mortality with radiotherapy versus chemotherapy only in early-stage patients (HR, 0.347, P < 0.001) or non-anthracycline-based versus anthracycline-based chemotherapy in early-stage (HR, 0.690, P = 0.001) and advanced-stage patients (HR, 0.678, P = 0.045) was maintained in patients of all ages. CONCLUSIONS: These findings support making treatment decisions based on disease-related risk factors rather than dichotomized chronological age. PATIENTS AND METHODS: Data on 2640 patients with extranodal nasal-type NK/T-cell lymphoma from the China Lymphoma Collaborative Group database were analyzed retrospectively. Age as a continuous variable was entered into the Cox regression model using penalized spline analysis to determine the association of age with overall survival (OS) and treatment benefits.

9.
J Bone Miner Res ; 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31610066

RESUMO

Bortezomib (Btz) is a proteasome inhibitor approved by the FDA to treat multiple myeloma. It also increases bone volume by promoting osteoblast differentiation and inhibiting osteoclastogenesis in mice. However, Btz has severe systemic adverse effects, which would limit its use as a bone anabolic agent. Here, we designed and synthesized a bone-targeted form of Btz by conjugating it to a bisphosphonate (BP) with no anti-resorptive activity. We report that BP-Btz inhibited osteoclast formation and bone resorption and stimulated osteoblast differentiation in vitro similar Btz. In vivo, BP-Btz increased bone volume more effectively than Btz in 3 mouse models: untreated wild-type mice, mice with ovariectomy, and aged mice with tibial factures. Importantly, BP-Btz had significantly less systemic side effects than Btz, including less thymic cell death, sympathetic nerve damage and thrombocytopenia, and improved survival rates in aged mice. Thus, BP-Btz represents a novel anabolic agent to treat conditions, such as postmenopausal and age-related bone loss. Bone-targeting is an attractive approach to repurpose approved drugs to treat skeletal diseases. This article is protected by copyright. All rights reserved.

10.
J Clin Pharmacol ; 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31648372

RESUMO

Six-month combination regimens could lead to serious hepatotoxicity, which may limit the clinical use of antituberculosis drugs. ABCC transporters are critical to the influx and efflux of compounds into and out of cells. The aim of this study was to explore whether the genetic variants in ABCC genes were related to the development of antituberculosis drug-induced hepatotoxicity. Here, we screened and genotyped 39 single-nucleotide polymorphisms of 13 ABCC genes in 746 eligible patients treated by first-line antituberculosis drugs in Western China Hospital. Genomic DNA was extracted from a peripheral blood sample of each patient, and clinical symptoms and laboratory results were recorded regularly. We found that the incidence rate of hepatotoxicity was 15.8% in the western Chinese Han population. As a result, the ABCC2 rs3740065 genotype, sex, and the baseline level of alanine aminotransferase are independent risk factors of antituberculosis drug-induced hepatotoxicity, with P values of .008, .014, and <.001, respectively. Our findings revealed a fraction of the underlying mechanism of hepatotoxicity, and larger validation studies on different populations are warranted to confirm these findings.

11.
J Biomed Sci ; 26(1): 79, 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31629407

RESUMO

BACKGROUND: Neuronal activity-induced changes in gene expression patterns are important mediators of neuronal plasticity. Many neuronal genes can be activated or inactivated in response to neuronal depolarization. Mechanisms that activate gene transcription are well established, but activity-dependent mechanisms that silence transcription are less understood. It is also not clear what is the significance of inhibiting these genes during neuronal activity. METHODS: Quantitative Real Time-PCR, western blot and immunofluorescence staining were performed to examine the expression of Senp1 and GluR1 in mouse cortical neurons. The alterations of Yy1 phosphorylation upon neuronal depolarization and the interaction of Yy1 with Brd4 were studied by protein co-immunoprecipitation. The regulators of Yy1 phosphorylation were identified by phosphatase inhibitors. Chromatin immunoprecipitation, in vitro DNA binding assay, luciferase assay and gene knockdown experiments were used to validate the roles of Yy1 and its phosphorylation as well as Brd4 in regulating Senp1 expression. RESULTS: We report that neuronal depolarization deactivates the transcription of the SUMO protease Senp1, an important component regulating synaptic transmission, scaling, and plasticity, through Yy1. In un-stimulated neurons, Senp1 transcription is activated by a Yy1-Brd4 transcription factor protein complex assembled on the Senp1 promoter. Upon membrane depolarization, however, Yy1 is dephosphorylated and the Yy1-Brd4 complex is evicted from the Senp1 promoter, reducing Senp1 transcription levels. Both Yy1 and Senp1 promote the expression of AMPA receptor subunit GluR1, a pivotal component in learning and memory. CONCLUSIONS: These results reveal an axis of Yy1/Brd4-Senp1 which regulates the expression of GluR1 during neuronal depolarization. This implicates a regulation mechanism in silencing gene expression upon neuronal activity.

12.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(4): 483-488, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31642223

RESUMO

OBJECTIVE: To study the application value of motion-correction phase sensitive inversion recovery (MOCO-PSIR) to evaluate myocardial fibrosis in the patients with heart failure caused by dilated cardiomyopathy (DCM). METHODS: A prospective study included 60 patients who underwent cardiac MRI enhanced scan from June 2017 to November 2018, including 38 patients who were clinically diagnosed with DCM and 22 patients in the normal control group. All patients were scanned with three late gadolinium enhancement (LGE) sequences: segmented-PSIR, single-shot-PSIR, MOCO-PSIR at the same time. The subjective quality score (level 4) and image signal-to-noise ratio (objective evaluation) of normal and abnormal myocardium were analyzed and compared in three scanning technique groups. The detection rate of myocardial fibrosis and image acquisition time of the three scanning techniques were recorded. RESULTS: In the normal control group (sinus rhythm), subjective score showed no statistical significance. Subjective scoring results in the patients with DCM: MOCO-PSIR>single-shot-PSIR> segmented-PSIR (P < 0.05). SNR results PSIR-LGE images in DCM patients as well as control group: segmented-PSIR>MOCO-PSIR> single-shot-PSIR (P < 0.05). In the whole 646 segments analysis of DCM patients, the ratio unable to judge in segmented-PSIR was up to 25.5%, but only 1.4% in MOCO-PSIR. Significant difference was found in the three groups. While in the 374 segments of control group, no statistical difference was found in comparison of incapability to judge. Acquisition time covered left ventricular: (5.6±1.7) min in segmented-PSIR, (0.4±0.2) min in single-shot-PSIR and (4.5±1.1) min in MOCO-PSIR. Pairwise comparison of acquisition time among three scanning techniques was statistically significant (P < 0.001). CONCLUSION: MOCO-PSIR-LGE has better clinical significance than conventional delayed enhanced scan sequences in the diagnosis of myocardial fibrosis in the patients with heart failure caused by dilated cardiomyopathy.

13.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(4): 494-499, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31642225

RESUMO

OBJECTIVE: To determine the myocardial texture features of cardiac magnetic resonance (CMR) in healthy adult Han populations. METHODS: 59 healthy Han volunteers were recruited for this study from May 2016 to November 2017. CMR examinations were performed on the participants with a 3.0T scanner (Tim Trio, Siemens Medical Solution) to estimate the functional parameters, Native T1 value and ECV. Texture analysis (TA) was performed on the region of interest (ROI) in the left ventricle myocardium on T1 mapping images, with 40 myocardial texture features being extracted. Differences in the myocardial texture features across gender and age groups were analyzed through Student's t-tests or Wilcoxon signed-rank tests. Spearman correlations were analyzed between the myocardial texture features and age, native T1 value and extracellular volume (ECV). RESULTS: Of the 59 participants, 28 were women and 29 were in the younger age group (< 45 years old). The male participants had higher left ventricular mass index (Lvmassi) and lower native T1 than their female counterparts (P < 0.01). No gender differences in blood pressure, heart rate, left ventricular ejection fraction (LVEF) and ECV values were found. Ten of the forty myocardial texture features showed gender differences, including two first order features and eight Grey-level co-occurrence matrix (GLCM) features. Gender differences appeared in five first order features and eight GLCM features in the younger group (< 45 years old), but not in the older group (≥45 years old). Eight myocardial texture features were correlated with age, including five first order features and three GLCM features (all P < 0.01). Six first-order texture features were correlated with Native T1 values of the left ventricle middle myocardium. Three first-order texture features were correlated with ECV. CONCLUSION: Myocardial texture features in T1 mapping images vary by gender and age in healthy Han populations.

14.
Biosens Bioelectron ; 145: 111563, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31574351

RESUMO

A critical barrier for the successful development of fiber sensors for bio-chemical processes is their limitedly improved sensitivity, restricted by the sensor structural design. To solve this, in this paper, a novel concept was proposed using functionalised modified magnetic microspheres (MMSs) to "amplify" the effect of target bio-chemical analytes to significantly improve the fiber sensor's sensitivity, which has been demonstrated using human chorionic gonadotropin (hCG) as an example. Two types of antibody hCG, (ß and α, both can specifically bind with hCG), were adhered on the surface of fibre sensor and MMSs respectively. Both hCG and MMSs will be specifically captured by the fibre sensor, where MMSs act as an "amplifier" to improve the sensor sensitivity. Experimentally immunomagnetic detection limit of 0.0001 mIU/mL has been achieved, which is the highest reported so far. This newly developed methodology opens a new direction for sensitivity improvement and could be further explored to applications require ultrahigh sensitivity detections such as earlier medical diagnostics.

15.
Food Funct ; 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31602443

RESUMO

The objective of this study was to investigate the effects of dietary intervention on intestinal microbiota-mediated change in short chain fatty acid (SCFA) profile and intestinal homeostasis. Sequencing of the 16S rDNA of gut bacteria, metagenomics, intestinal epithelial transcriptomics, and metabonomics were conducted. Results showed that the dietary interventions altered the microbiota composition of cecal digesta, microbiota-mediated metabolism, and the gene expression profile in intestinal epithelial cells. Compared with red meat-diet-fed mice, fiber-diet-fed mice presented a shift in the gut microbiome toward increased production of butanoate, which was accompanied by up-regulation of microbiota- and AMP-activated protein kinase (AMPK)-dependent gene expression and decrease in serum concentrations of trimethylamine N-oxide (TMAO), triglyceride (TG) and glucose (GLU). The results suggested a new regulatory mechanism via which butanoate and AMPK activation contributed to intestinal integrity and homeostasis by affecting metabolism, intestinal barrier function and transporter expression.

16.
Inorg Chem ; 58(18): 12415-12421, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31483642

RESUMO

Many strategies to optimize molybdenum selenide based electrocatalysts for hydrogen evolution reaction (HER) have been explored; however, the modulation of molybdenum selenide on the molecular scale remains an ongoing challenge. Here, we synthesized a new molecular HER electrocatalyst based on a molybdenum-selenium cluster (Mo3Se13) and further realized its modulation by precise sulfur substitution at the molecular level to enhance the HER activity. The density functional theory (DFT) calculations demonstrated that the substituted sulfur could promote the hydrogen adsorption process and thus improve the HER performance. This work not only realizes the selective replacement of the bridging selenium atom with a sulfur atom in the molybdenum-selenium cluster for the first time but also provides a precise model for illustrating the structure-property relationship in electrocatalysis on the molecular level.

17.
Biosci Biotechnol Biochem ; : 1-9, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31490096

RESUMO

Plumbagin (PLB), an alkaloid obtained from the roots of the plants of Plumbago genus, is an inhibitor of NADPH oxidase 4 (NOX4). This study aimed to investigate the beneficial effect of PLB against oxygen-glucose deprivation/reoxygenation (OGDR)-induced neuroinjury in human SH-SY5Y neuronal cultures. Our results showed that OGD/R stimulated NOX4 protein expression and reactive oxygen species (ROS) production in SH-SY5Y cells, whereas increased 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) production, resulting in the activation of the NLRP3 inflammasome. And PLB pretreatment reduced the ROS production by regulating the expression of NOX4 and downregulated NF-κB signaling which was induced by OGDR. Furthermore, PLB inhibited OGDR induced NLRP3 inflammasome activation but not PARP1. Overall, PLB improved OGDR induced neuroinjury by inhibiting NOX4-derived ROS-activated NLRP3 inflammasome.

18.
Am J Hypertens ; 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31504137

RESUMO

BACKGROUND: While sex differences characterize susceptibility and severity of idiopathic pulmonary arterial hypertension (IPAH), our understanding of the relationship between levels of gonadotropins and sex hormones in fertile women and the disease is limited. We aimed to investigate whether gonadotropin and sex hormone levels in women of reproductive age were associated with risk and mortality of IPAH. METHODS: We did a matched case-control study. Cases were reproductive female patients with idiopathic pulmonary arterial hypertension admitted in Shanghai Pulmonary Hospital (Tongji University School of Medicine, Shanghai, China) during 2008 to 2014. Healthy controls were matched on age and body mass index. We also did a prospective cohort study to assess the effects of hormone levels on mortality in IPAH fertile female patients. RESULTS: 164 cases and 133 controls were included. After adjustment for age and body mass index, the odds ratios of having IPAH for follicle stimulating hormone, testosterone, and progesterone as expressed on natural log scale were 1.51 (95%CI 1.06, 2.16), 0.42 (0.31-0.57), and 0.52(0.43-0.63), respectively. In the cohort study with a median follow up of 77-months, the hazard ratios for dying after adjustment for baseline characteristics and treatments among IPAH patients were 2.01 (95% CI: 1.22-3.30) and 0.78 (95% CI: 0.62-0.98) for follicle stimulating hormone and progesterone in natural log scale, respectively. CONCLUSIONS: In reproductive women with IPAH, high follicle stimulating hormone and low progesterone tended to be associated with high risk of IPAH and mortality among patients.

19.
PLoS One ; 14(9): e0222033, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31490979

RESUMO

BACKGROUND: Pregnane X receptor (PXR) regulates the expression of drug-metabolizing enzymes and transport enzymes. NF-κB not only plays a role in liver homeostasis and injury-healing processes by regulating inflammatory responses but may also regulate the transcription of PXR. Currently, genetic polymorphisms in PXR are associated with adverse drug effects. Because little is known about the association between NF-κB1 genetic polymorphisms and adverse drug reactions, we explored the association between PXR and NF-κB1 single nucleotide polymorphisms (SNPs) and susceptibility to anti-tuberculosis drug-induced liver injury (ATDILI). MATERIALS AND METHODS: A total of 746 tuberculosis patients (118 with ATDILI and 628 without ATDILI) were prospectively enrolled at West China Hospital between December 2014 and April 2018. Nine selected SNPs (rs3814055, rs13059232, rs7643645 and rs3732360 in PXR and rs78872571, rs4647992, rs60371688, rs1598861 and rs3774959 in NF-κB1) were genotyped with a custom-designed 2x48-plex SNP Scan TM Kit. The frequencies of the alleles, genotypes and genetic models of the variants were compared between patients with or without ATDILI, while joint effect analysis of the SNP-SNP interactions was performed using multiplicative and additive models. The odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated. RESULTS: The T allele of rs3814055 in PXR was associated with a decreased risk for ATDILI (OR 0.61; 95% CI: 0.42-0.89, p = 0.0098). The T alleles of rs78872571 and rs4647992 in NF-κB1 were significantly associated with an increased risk for ATDILI (OR 1.91; 95% CI: 1.06-3.43, p = 0.028 and OR 1.81; 1.06-3.10, p = 0.029, respectively). The allele, genotype and genetic model frequencies were similar in the two groups for the other six SNPs (all P>0.05). There were no multiplicative or additive interactions between the SNPs. CONCLUSION: Our study is the first to reveal that rs3814055 variants in PXR and rs78872571 and rs4647992 variants in NF-κB1 are associated with susceptibility to ATDILI caused by first-line anti-tuberculosis combination treatment in the Han Chinese population.

20.
Urol J ; 16(5): 417-426, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31473994

RESUMO

PURPOSE: This study reviewed the efficacy and safety of the microsurgical subinguinal varicocelectomy (MSV) with and without testicular delivery (TD) for varicocele patients. MATERIALS AND METHODS: A systematic literature search was conducted in EMBASE, PubMed, MEDLINE, Cochrane databases, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), and Google Scholar databases to identify relevant studies that reported MSV with and without TD for varicocele patients published in English or Chinese up to October 2018. The Newcastle-Ottawa Scale (NOS) and the Jadad scores were used to evaluate the methodological quality of all the included studies. We also used the Cochrane Collaboration's tool for assessing risk of bias for each study. The Review Manager Software version 5.3 was used to conduct data analysis. RESULTS: Four RCTs and three retrospective studies consisting of 993 patients were included. Meta-analysis results indicated that both of the two treatments were effective and safe. MSV with TD had a lower recurrence rate (OR = 0.20, 95% CI: 0.06 - 0.65, P = .007, I2 = 0%) and postoperative serum testosterone level (MD = -39.07, 95% CI: -51.95 - -26.18, P = .00001, I2 = 0%) compared with MSV without TD but was associated with higher postopera-tive complications rate (OR=7.35, 95% CI: 2.92-18.53, P < .0001, I2 = 0%). We found no significant differences in operation time (MD = 12.46, 95% CI:0.11-24.81,P= .05, I2 = 87%), sperm concentration (MD = 3.73, 95% CI: -2.88 - 10.35, P = .27, I2 = 81%), sperm motility (MD = 10.96, 95% CI: -11.93 - 33.86, P = .35, I2 = 99%), and pregnancy rate(OR = 0.65, 95% CI: 0.37- 1.16, P = .15, I2 = 0%). CONCLUSION: This meta-analysis compared efficacy and safety of MSV with and without TD for varicocele pa-tients. MSV with TD was associated with a higher postoperative complication rate but lower recurrence rate and postoperative serum testosterone level than MSV without TD. In terms of preoperative serum testosterone level, operation time, sperm concentration, sperm motility, and pregnancy rate, we found no significant differences.

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