Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.538
Filtrar
1.
J Adolesc Health ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33039270

RESUMO

PURPOSE: The main objectives of this study were to determine (1) whether family communication and school connectedness offer protection against suicidal behaviors in the presence of adverse childhood experiences (ACEs; direct protective effect) and (2) whether family communication or school connectedness buffer the association between ACEs and suicidal behaviors (interacting protective effect) on the multiplicative and additive scales. METHODS: Data were obtained from a western state's 2019 Youth Risk Behavior Survey that included 5,341 middle school and 4,980 high school participants. Generalized linear models were used to estimate whether family communication and school connectedness offered direct protection against suicidal behaviors or buffered the association between ACEs and suicidal behaviors using adjusted prevalence ratios and corresponding 95% confidence intervals. RESULTS: Family communication and school connectedness offered direct protection against suicidal behaviors in the presence of ACEs (a 1-unit higher score was associated with a 32%-42% lower prevalence of suicidal behaviors for middle school youth and a 27%-39% lower prevalence of suicidal behaviors for high school youth). There was evidence that family communication and school connectedness buffered the association between ACEs and suicidal behaviors on the multiplicative scale. CONCLUSIONS: The findings provide support for the development and implementation of interventions that build family communication and school connectedness to reduce suicidal behaviors. Furthermore, screening for trauma and suicidal behaviors is warranted.

2.
Zhongguo Yi Liao Qi Xie Za Zhi ; 44(5): 409-414, 2020 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-33047563

RESUMO

We use a dense and fully connected convolutional network with good feature learning in small samples, to automatically pre-deline CTV of cervical cancer patients based on CT images and evaluate the effect. The CT data of stage IB and IIA postoperative cervical cancer with similar delineation scope were selected to be used to evaluate the pre-sketching accuracy from three aspects:sketching similarity, sketching offset and sketching volume difference. It has been proved that the 8 most representative parameters are superior to those with single network and reported internationally before. Dense V-Net can accurately predict CTV pre-delineation of cervical cancer patients, which can be used clinically after simple modification by doctors.

3.
Colloids Surf B Biointerfaces ; 197: 111358, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-33068823

RESUMO

More effective strategies are needed to improve the treatment of liver cancer. Sono-photodynamic therapy (SPDT) has a more obvious antitumor effect than sonodynamic therapy (SDT) or photodynamic therapy (PDT). We aimed to investigate Glypican-3-targeted, curcumin-loaded microbubbles (GPC3-CUR-MBs)-mediated SPDT in liver cancer cells in vitro and in vivo. GPC3-CUR-MBs were prepared by streptavidin-biotin interactions and the immune ligation method. The characterization and toxicity of GPC3-CUR-MBs and the anti-liver cancer effects of GPC3-CUR-MB-mediated SPDT in vitro and in vivo were studied. We synthetized GPC3-CUR-MBs and found that GPC3-CUR-MBs had no significant toxicity to HepG2 liver cancer cells. In terms of the anti-liver cancer effects in vitro and in vivo, when we used CUR, CUR-MBs or GPC3-CUR-MBs as the sono/photosensitizers, the outcome of SPDT was superior to that of SDT or PDT alone. The outcomes with GPC3-CUR-MBs were better than those with CUR or CUR-MBs in the SDT, PDT or SPDT groups. During the treatment period, the weight of the HepG2 tumor-bearing mice did not decrease significantly, and no significant evidence of lung, heart, liver, spleen and kidney damage was found with H&E staining. Our results indicated that the anti-liver tumor effect of SPDT was better than that of SDT and PDT and that GPC3-CUR-MBs were promising sono/photosensitizers.

4.
J Hazard Mater ; 404(Pt B): 124014, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33069998

RESUMO

Molybdenum disulfide nanoparticles (MoS2 NPs) has emerged as the promising nanomaterial with a wide array of applications in the biomedical, industrial and environmental field. However, the potential effect of MoS2 NPs on marine organisms has yet to be reported. In this study, the effect of MoS2 NPs on the physiological index, subcellular morphology, transcriptomic profiles of the marine microalgae Dunaliella salina was investigated for the first time. exhibited "doping-like" effects on marine microalgae; Growth stimulation was 193.55%, and chlorophyll content increased 1.61-fold upon the addition of 50 µg/L MoS2 NPs. Additionally, exposure to MoS2 NPs significantly increased the protein and carbohydrate content by 2.03- and 1.56-fold, respectively. The antioxidant system was activated as well to eliminate the adverse influence of reactive oxygen species (ROS). Transcriptomic analysis revealed that genes involved in porphyrin synthesis, glycolysis/gluconeogenesis, tricarboxylic acid cycle and DNA replication were upregulated upon MoS2 NPs exposure, which supports the mechanistic role of MoS2 NPs in improving cellular growth and photosynthesis. The "doping-like" effects on marine algae suggest that the low concentration of MoS2 NPs might change the rudimentary ecological composition in the ocean.

5.
Nucleic Acids Res ; 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33080033

RESUMO

Core regulatory circuitry (CRC)-dependent transcriptional network is critical for developmental tumors in children and adolescents carrying few gene mutations. However, whether and how CRC contributes to transcription regulation in Ewing sarcoma is unknown. Here, we identify and functionally validate a CRC 'trio' constituted by three transcription factors (TFs): KLF15, TCF4 and NKX2-2, in Ewing sarcoma cells. Epigenomic analyses demonstrate that EWS-FLI1, the primary fusion driver for this cancer, directly establishes super-enhancers of each of these three TFs to activate their transcription. In turn, KLF15, TCF4 and NKX2-2 co-bind to their own and each other's super-enhancers and promoters, forming an inter-connected auto-regulatory loop. Functionally, CRC factors contribute significantly to cell proliferation of Ewing sarcoma both in vitro and in vivo. Mechanistically, CRC factors exhibit prominent capacity of co-regulating the epigenome in cooperation with EWS-FLI1, occupying 77.2% of promoters and 55.6% of enhancers genome-wide. Downstream, CRC TFs coordinately regulate gene expression networks in Ewing sarcoma, controlling important signaling pathways for cancer, such as lipid metabolism pathway, PI3K/AKT and MAPK signaling pathways. Together, molecular characterization of the oncogenic CRC model advances our understanding of the biology of Ewing sarcoma. Moreover, CRC-downstream genes and signaling pathways may contain potential therapeutic targets for this malignancy.

6.
Can Respir J ; 2020: 2379814, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33082890

RESUMO

Background: Tracheal stenosis is able to lead to airway obstruction. Objective: To evaluate the efficacy and safety profile of Montgomery T-tube implantation in patients with tracheal stenosis. Methods: Fifty-two patients with tracheal stenosis diagnosed between 2016 and 2019 were included in this retrospective cohort study. The patients were divided into observation group (n = 25 cases) and control group (n = 27). The therapeutic effect, arterial blood gas analysis, arterial oxygen partial pressure (PaO2), arterial carbon dioxide partial pressure (PaCO2), shortness of breath score, airway diameter change, dyspnea score, quality of life, and safety were compared between the two groups before and after treatment. Results: The therapeutic effect of the observation group gained better results than that of the control group (84.00% vs. 62.96%). One week after operation, the pH value, SaO2, PaCO2, shortness of breath score, airway diameter change, dyspnea score, life quality, and incidence of postoperative complications in the observation group exerted better results as compared to the control group. Conclusion: The implantation of Montgomery T-tube has effective function in terms of improving the symptoms of dyspnea and the life quality of patients with safety profile in patients harboring tracheal stenosis.

7.
Cell Death Discov ; 6: 94, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33083016

RESUMO

Postoperative pancreatic fistula (POPF) is a common and dreaded complication after pancreaticoduodenectomy (PD). The gut microbiota has been considered as an crucial mediator of postoperative complications, however, the precise roles of gut microbiota in POPF are unclear. A prospective study was developed to explore the effects of somatostatin on gut microbiota and we aim to identify the microbial alterations in the process of POPF. A total of 45 patients were randomly divided into PD group or additional somatostatin therapy group. The fecal sample of each patient was collected preoperatively and postoperatively and the gut microbiota was analyzed by 16S rRNA sequencing. Our study found that somatostatin therapy was independent risk factor for the occurrence of POPF, and it reduced the microbial diversity and richness in patients. At genus level, somatostatin therapy led to a decreased abundance in Bifidobacterium, Subdoligranulum and Dubosiella, whereas the abundance of Akkermansia, Enterococcus and Enterobacter were increased. The abundance levels of certain bacteria in the gut microbiota have significantly shifted in patients with POPF. The LEfSe analysis revealed that Ruminococcaceae could be used as microbial markers for distinguishing patients with high risk of POPF. Furthermore, Verrucomicrobia and Akkermansia could be used as preoperative biomarkers for identifying patients without POPF. Our prospective study highlights the specific communities related with somatostatin therapy and discovers POPF-associated microbial marker, which suggests that gut microbiota may become a diagnostic biomarker and potential therapeutic target for POPF.

9.
Eur J Radiol ; 132: 109303, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-33017773

RESUMO

PURPOSE: To develop and evaluate an automatic measurement model for hip joints based on anteroposterior (AP) pelvic radiography and a deep learning algorithm. METHODS: A total of 1260 AP pelvic radiographs were included. 1060 radiographs were randomly sampled for training and validation and 200 radiographs were used as the test set. Landmarks for four commonly used parameters, such as the center-edge (CE) angle of Wiberg, Tönnis angle, sharp angle, and femoral head extrusion index (FHEI), were identified and labeled. An encoder-decoder convolutional neural network was developed to output a multi-channel heat map. Measurements were obtained through landmarks on the test set. Right and left hips were analyzed respectively. The mean of each parameter obtained by three radiologists was used as the reference standard. The Percentage of Correct Key points (PCK), intraclass correlation coefficient (ICC), Pearson correlation coefficient (r), root mean square error (RMSE), mean absolute error (MAE), and Bland-Altman plots were used to determine the performance of deep learning algorithm. RESULTS: PCK of the model at 3 mm distance threshold range was from 87 % to 100 %. The CE angle, Tönnis angle, Sharp angle and FHEI of the left hip generated by the model were 29.8°±6.1°, 5.6°±4.2°, 39.0°±3.5° and 19 %±5 %, respectively. The parameters of the right hip were 30.4°±6.1°, 7.1°±4.4°, 38.9°±3.7° and 18 %±5 %. There were good correlation and consistency of the four parameters between the model and the reference standard (ICC 0.83-0.93, r 0.83-0.93, RMSE 0.02-3.27, MAE 0.02-1.79). CONCLUSIONS: The new developed model based on deep learning algorithm can accurately identify landmarks on AP pelvic radiography and automatically generate parameters of hip joint. It will provide convenience for clinical practice of measurement.

10.
Pharmacol Res ; : 105111, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33065284

RESUMO

Macrophages, a type of myeloid immune cell, play essential roles in fighting against pathogenic invasion and activating T cell-mediated adaptive immune responses. As a major constituent of the tumor microenvironment (TME), macrophages play a complex role in tumorigenesis and tumor progression. They can inhibit tumor growth by releasing proinflammatory cytokines and exerting cytotoxic activities but principally contribute to tumor progression by promoting tumor proliferation, angiogenesis, and metastasis. The tumor-promoting hallmarks of macrophages have aroused widespread interest in targeting tumor-associated macrophages (TAMs) for cancer immunotherapy. Increasing preclinical and clinical studies suggest that TAMs are a promising target for cancer immunotherapy. To date, TAM-targeted therapeutic strategies have mainly been divided into two kinds: inhibiting pro-tumor TAMs and activating anti-tumor TAMs. We reviewed the heterogeneous and plastic characteristics of macrophages in the TME and the feasible strategies to target TAMs in cancer immunotherapy and summarized the complementary effect of TAM-targeted therapy with traditional treatments or other immunotherapies.

11.
J Neuroinflammation ; 17(1): 306, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33059704

RESUMO

BACKGROUND: Retinitis pigmentosa (RP) is a group of inherited eye disorders with progressive degeneration of photoreceptors in the retina, ultimately leading to partial or complete blindness. The mechanisms underlying photoreceptor degeneration are not yet completely understood. Neuroinflammation is reported to play a pathological role in RP. However, the mechanisms that trigger neuroinflammation remain largely unknown. To address this question, we investigated the role of cyclooxygenase-1 (COX-1), a key enzyme in the conversion of arachidonic acid to proinflammatory prostaglandins, in the rd10 mouse model of RP. METHODS: We backcrossed COX-1 knockout mice (COX-1-/-) onto the rd10 mouse model of RP and investigated the impact of COX-1 deletion on neuroinflammation in the resulting COX-1-/-/rd10 mouse line, using a combination of immunocytochemistry, flow cytometry, qPCR, ELISA, and a series of simple visual tests. RESULTS: We found that genetic ablation or pharmacological inhibition of COX-1 alleviated neuroinflammation and subsequently preserved retinal photoreceptor and function and visual performance in rd10 mice. Moreover, we observed that the pharmacological inhibition of the prostaglandin E2 (PGE2) EP2 receptors largely replicated the beneficial effects of COX-1 deletion, suggesting that EP2 receptor was a critical downstream effector of COX-1-mediated neurotoxicity in rd10 mice. CONCLUSION: Our data suggest that the COX-1/PGE2/EP2 signaling pathway was partly responsible for significantly increased neuroinflammation and disease progression in rd10 mice, and that EP2 receptor could be targeted therapeutically to block the pathological activity of COX-1 without inducing any potential side effects in treating RP patients.

12.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(10): 1105-1108, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33059808

RESUMO

OBJECTIVE: To study the clinical features of children with influenza and plastic bronchitis (PB). METHODS: A retrospective analysis was performed on the medical data of 63 children with influenza and PB, including clinical manifestations, laboratory examination results, imaging findings, treatment, and outcome. RESULTS: Among the 63 children, there were 52 boys (83%) and 11 girls (17%), and 42 children had influenza A and 21 had influenza B. Among these children, 38 (60%) aged 3-6 years, and 15 (24%) had underlying diseases. The main clinical manifestations were high fever (90%), cough (95%), and shortness of breath (73%). Twenty-four children (38%) were found to have atelectasis by imaging examination. Auscultation showed that 16 children (25%) had no rales in the lungs. Of all children, 41 were admitted to the intensive care unit, and 32 required mechanical ventilation. All children underwent fiberoptic bronchoscopy and alveolar lavage. Among the 63 children, 60 recovered and 3 died. CONCLUSIONS: Influenza with PB is often observed in boys and preschool children. For influenza children with shortness of breath, even if there is no atelectasis on chest X-ray or no rales are found by auscultation, the possibility of PB still needs to be considered.

13.
JAMA Surg ; : e204103, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33026457

RESUMO

Importance: Image-guided breast biopsy of a residual imaging abnormality or tumor bed after neoadjuvant chemotherapy (NACT) is increasingly used to assess residual cancer, facilitate risk-adaptive surgery, and potentially identify exceptional responders in whom local therapy may be de-escalated. Objective: To further assess the accuracy of post-NACT image-guided biopsy to predict residual cancer in the breast. Design, Setting, and Participants: This diagnostic study analyzed multicenter patient-level data of patients with breast cancer who were treated with NACT and underwent image-guided biopsy before surgery at Royal Marsden Hospital in London, UK; Seoul National University Hospital in Seoul, South Korea; and MD Anderson Cancer Center in Houston, Texas. Data were analyzed from June to July 2019. Main Outcomes and Measures: Diagnostic accuracy of post-NACT image-guided biopsy. Final surgical pathology was used as reference standard. Results: Data from 166 women were analyzed. The median (range) age was 49 (25-76) years. The median (range) tumor size on pretreatment and posttreatment imaging was 33.5 (12-100) mm and 10 (0-100) mm, respectively. The overall pathologic complete response rate was 51.2% (n = 85) (16.1% [5 of 31] for hormone receptor-positive/ERBB2 (formerly HER2)-negative; 44.7% [21 of 47] for hormone receptor-positive/ERBB2-positive; 69% [20 of 29] for hormone receptor-negative/ERBB2-positive; and 66.1% [39 of 59] for triple negative). The majority (143 [86.1%]) underwent image-guided vacuum-assisted biopsy (VAB), and 23 had core-cut biopsy. The median (range) needle gauge was 10 (7-14), and the median (range) number of samples was 6 (2-18). When image-guided biopsy (VAB and core-cut biopsy) was representative (159 [95.8%]), the false-negative rate across the whole cohort was 18.7% (95% CI, 10.6%-29.3%). Subgroup analysis of patients with a complete/partial clinical response and residual imaging abnormality of 2 cm or smaller with at least 6 VABs taken (76 [45.8%]) demonstrated a false-negative rate of 3.2% (95% CI, 0.1%-16.7%), a negative predictive value of 97.4% (95% CI, 86.5%-99.9%), and an overall accuracy of 89.5% (95% CI, 80.3%-95.3%). Conclusions and Relevance: This large multicenter pooled data analysis suggests that a standardized protocol using image-guided VAB of a tumor bed measuring 2 cm or smaller with 6 or more representative samples allows reliable prediction of residual disease. These results could inform the design of de-escalation trials in NACT exceptional responders testing the safety of eliminating surgery.

14.
Chemosphere ; 264(Pt 2): 128557, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33049504

RESUMO

Capacitive deionization (CDI) is a promising method to remove metal contaminants in water. Herein, we report on the preparation of activated carbon from cation-exchange resin by introducing ZnCl2 via ion exchange followed by heat treatment and CO2 activation, which is evaluated for removal of Cu2+ in water via CDI technology. The results have shown that both the heat treatment and the CO2 activation are helpful to tune the pore structure of the activated carbons in terms of ions adsorption and transportation. The activated carbon prepared by heat treatment at 600 °C and CO2 activation at 750 °C, named as AC-600-750, has the highest specific surface area of 1162 m2 g-1 and a specific capacitance of 247.4 F g-1 at 50 mV-1, with a Cu2+ adsorption capacity of 77.8 mg g-1 at 1.2 V in 50 mg L-1 CuCl2 solution that is much higher than that of the commercial activated carbon. The electrosorption of Cu2+ ions over activated carbon follows a monolayer adsorption scheme, of which the kinetic can be well explained by pseudo-first-order kinetic model. The resin-based activated carbons are of potential as an electrode material for efficient removal of heavy metal from contaminated water by CDI process.

15.
Eur J Med Chem ; 209: 112842, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-33065375

RESUMO

Ferroptosis is a new type of programmed cell death discovered recently and has been demonstrated to be involved in a number of human diseases such as ischemic stroke. Ferroptosis inhibitors are expected to have potential to treat these diseases. Herein, we report the identification of promethazine derivatives as a new type of ferroptosis inhibitors. Structure-activity relationship (SAR) analyses led to the discovery of the most potent compound 2-(1-(4-(4-methylpiperazin-1-yl)phenyl)ethyl)-10H-phenothiazine (51), which showed an EC50 (half maximal effective concentration) value of 0.0005 µM in the erastin-induced HT1080 cell ferroptosis model. In the MCAO (middle cerebral artery occlusion) ischemic stroke model, 51 presented an excellent therapeutic effect. This compound also displayed favorable pharmacokinetic properties, in particular, a good ability to permeate the blood-brain barrier. Overall, 51 could be a promising lead compound for the treatment of ferroptosis related diseases and deserves further investigations.

16.
Molecules ; 25(20)2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33076563

RESUMO

In order to explore highly efficient flame-retardant rigid polyurethane foam (RPUF), phosphorus/nitrogen compounds and expandable graphite (EG) were successfully incorporated into RPUF by a free one-spot method. The combustion results showed that the fire safety of the RPUF samples was remarkably improved by the addition of phosphoric/nitrogen compounds and EG. With the incorporation of 22.4 wt.% phosphorus/nitrogen compounds and 3.2 wt.% EG, the RPUF composites achieved UL-94 V-0 rating. Besides, the total heat release and total smoke release of RPUF composites were reduced by 29.6% and 32.4% respectively, compared to those of the pure RPUF sample. PO• and PO2• together with nonflammable gaseous products were evolved from phosphoric/nitrogen compounds in the gas phase, which quenched the flammable free radicals in the matrix and diluted the concentration of combustible gaseous products generated from PRUF during combustion. The compact char residues which acted as excellent physical barriers were formed by catalysis of EG and phosphoric/nitrogen compounds in the condense phase. The fire hazard of RPUF was significantly reduced by the synergistic effect of phosphorus-nitrogen compounds and EG. This work provides a promising strategy to enhance the fire safety of RPUF.

17.
Nat Commun ; 11(1): 5267, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33077711

RESUMO

Peroxisomes perform beta-oxidation of branched and very-long chain fatty acids, which leads to the formation of reactive oxygen species (ROS) within the peroxisomal lumen. Peroxisomes are therefore prone to ROS-mediated damages. Here, using light to specifically and acutely induce ROS formation within the peroxisomal lumen, we find that cells individually remove ROS-stressed peroxisomes through ubiquitin-dependent pexophagy. Heat shock protein 70 s mediates the translocation of the ubiquitin E3 ligase Stub1 (STIP1 Homology and U-Box Containing Protein 1) onto oxidatively-stressed peroxisomes to promote their selective ubiquitination and autophagic degradation. Artificially targeting Stub1 to healthy peroxisomes is sufficient to trigger pexophagy, suggesting a key role Stub1 plays in regulating peroxisome quality. We further determine that Stub1 mutants found in Ataxia patients are defective in pexophagy induction. Dysfunctional peroxisomal quality control may therefore contribute to the development of Ataxia.

18.
Artigo em Inglês | MEDLINE | ID: mdl-33050867

RESUMO

BACKGROUND: Enhanced expression and activation of metalloproteinase-9 (MMP9) is associated with mantle cell lymphoma (MCL) progression, invasion and metastasis. OBJECTIVE: To find potential peptide inhibitor against MMP9, which in turn, could inhibit MCL progression. METHODS: We performed CCK8 assay, western blot and transwell assays for RNAi activity. Molecular Operating Environment (MOE) software was applied for structural optimization as MMP9 and peptides were docked. We used gelatin zymography and confocal microscopy confirm that the peptides can inhibit MMP9 activity. We applied CCK8 and transwell assay to evaluate cell proliferation and metastasis and flow cytometry to evaluate cell cycle progression and apoptosis. RESULTS: High MMP9 expression was observed in 49 of 88 samples (55.7%). Patients with high MMP9 expression were more likely to present with high stage (Stage 3-4, P=0.01), bone marrow invasion (P=0.033) and high level LDH (P=0.000). High MMP9 expression was associated with significantly shorter overall survival (OS, HR=2.378, P=0.012) and progression free survival (PFS, HR=2.068, P=0.03). Multivariate analysis identified high MMP9 expression (P= 0.027), high-risk mantle cell lymphoma international prognostic index (MIPI, HR=2.327, P=0.023), and no radiation therapy (P=0.035) as adverse prognostic factors. Silencing of MMP9 in Jeko-1 cells by RNAi suppressed cells migration and invasion in vitro (P<0.05). According to the docking results, peptide M3 bound deeply in the binding pocket of MMP9 and had interaction with the active-site Zn2+ ion in the catalytic domain. M3 was not only compatible with MMP9, but also inhibited its activity. M3 inhibited Jeko-1 cells proliferation, metastasis and cell cycle progression, and promoted cell apoptosis rate (P<0.05). CONCLUSION: We designed M3 through structure-based molecular docking, which can specifically bind to MMP9 and inhibit the activity of MMP9. M3 could be a potential antagonist as the treatment of MCL with MMP9 overexpression.

19.
Mol Med Rep ; 22(5): 4340-4350, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000265

RESUMO

Treatment­resistant schizophrenia (TRS) is a common phenotype of schizophrenia that places a considerable burden on patients as well as on society. TRS is known for its tendency to relapse and uncontrollable nature, with a poor response to antipsychotics other than clozapine. Therefore, it is urgent to identify objective biological markers, so as to guide its treatment and associated clinical work. In the present study, the peripheral blood mononuclear cells (PBMCs) of patients with TRS and a healthy control group, which were gender­, age­ and ethnicity­matched, were subjected to microRNA (miRNA/miR) sequencing to screen out the top three miRNAs with the highest fold change values. These were then validated in the TRS (n=34) and healthy control (n=31) groups by reverse transcription­quantitative PCR. For two of the top three miRNAs, the PCR results were in accordance with the sequencing result (P<0.01), while the third miRNA exhibited the opposite trend (P<0.01). To elucidate the functions of these two miRNAs, Homo sapiens (hsa)­miR­218­5p and hsa­miR­1262 and their regulatory network, target gene prediction was first performed using online TargetScan and Diana­micro T software. Bioinformatics analysis was then performed using functional enrichment analysis to determine the Gene Ontology terms in the category biological process and the Kyoto Encyclopedia of Genes and Genomes pathways. It was revealed that these target genes were markedly associated with the nervous system and brain function, and it was obvious that the differentially expressed miRNAs most likely participated in the pathogenesis of TRS. A receiver operating characteristic curve was generated to confirm the distinct diagnostic value of these two miRNAs. It was concluded that aberrantly expressed miRNAs in PMBCs may be implicated in the pathogenesis of TRS and may serve as specific peripheral blood­based biomarkers for the early diagnosis of TRS.

20.
J Am Soc Nephrol ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023926

RESUMO

BACKGROUND: Slopes of eGFR have been associated with increased risks of death and cardiovascular events in a U-shaped fashion. Poor outcomes in individuals with rising eGFR are potentially attributable to sarcopenia, hemodilution, and other indicators of clinical deterioration. METHODS: To investigate the association between eGFR slopes and risks of death or cardiovascular events, accounting for multiple confounders, we studied 2738 individuals with moderate to severe CKD participating in the multicenter Chronic Renal Insufficiency Cohort (CRIC) Study. We used linear, mixed-effects models to estimate slopes with up to four annual eGFR assessments, and Cox proportional hazards models to investigate the association between slopes and the risks of death and cardiovascular events. RESULTS: Slopes of eGFR had a bell-shaped distribution (mean [SD], -1.5 [-2] ml/min per 1.73 m2 per year). Declines of eGFR that were steeper than the average decline associated with progressively increasing risks of death (hazard ratio [HR], 1.23; 95% confidence interval [95% CI], 1.09 to 1.39; for a slope 1 SD below the average) and cardiovascular events (HR, 1.19; 95% CI, 1.03 to 1.38). Rises of eGFR or declines lower than the average decline were not associated with the risk of death or cardiovascular events. CONCLUSIONS: In a cohort of individuals with moderate to severe CKD, we observed steep declines of eGFR were associated with progressively increasing risks of death and cardiovascular events; however, we found no increased risks associated with eGFR improvement. These findings support the potential value of eGFR slopes in clinical assessment of adults with CKD.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA