MicroRNAs (miRNAs) are believed to have fundamental roles in tumorigenesis and have great potential for the diagnosis and treatment of cancer. However, the roles of miRNAs in hepatocellular ...carcinogenesis are still not fully elucidated. We investigated the aberrantly expressed miRNAs involved in hepatoma by comparison of miRNA expression profiles in cancerous hepatocytes with normal primary human hepatocytes, and 37 dysregulated miRNAs were screened out by twofold change with a significant difference (P<0.05). Clustering analysis based on 13 miRNAs with changes over 15-folds showed that the miRNA expression patterns between the cancerous and normal hepatocytes were clearly different. Among the 13 miRNAs, we found that miR-375 was significantly downregulated in hepatocellular carcinoma (HCC) tissues and cell lines. Overexpression of miR-375 in liver cancer cells decreased cell proliferation, clonogenicity, migration/invasion and also induced G1 arrest and apoptosis. To unveil the molecular mechanism of miR-375-mediated phenotype in hepatoma cells described above, we examined the putative targets using bioinformatics tools and found that astrocyte elevated gene-1 (AEG-1) was a potential target of miR-375. Then we demonstrated that miR-375 bound directly to the 3'-untranslated region of AEG-1 and inhibited the expression of AEG-1. TaqMan quantitative reverse transcriptase-PCR and western blot analysis showed that miR-375 expression was inversely correlated with AEG-1 expression in HCC tissues. Knockdown of AEG-1 by RNAi in HCC cells, similar to miR-375 overexpression, suppressed tumor properties. Ectopic expression of AEG-1, conversely, could partially reverse the antitumor effects of miR-375. In a mouse model, therapeutic administration of cholesterol-conjugated 2'-O-methyl-modified miR-375 mimics (Chol-miR-375) could significantly suppress the growth of hepatoma xenografts in nude mice. In conclusion, our findings indicate that miR-375 targets AEG-1 in HCC and suppresses liver cancer cell growth in vitro and in vivo, and highlight the therapeutic potential of miR-375 in HCC treatment.
Magnetic Weyl semimetal phase in a Kagomé crystal Liu, D F; Liang, A J; Liu, E K ...
Science (American Association for the Advancement of Science),
09/2019, Letnik:
365, Številka:
6459
Journal Article
Recenzirano
Odprti dostop
Weyl semimetals are crystalline solids that host emergent relativistic Weyl fermions and have characteristic surface Fermi-arcs in their electronic structure. Weyl semimetals with broken time ...reversal symmetry are difficult to identify unambiguously. In this work, using angle-resolved photoemission spectroscopy, we visualized the electronic structure of the ferromagnetic crystal Co
Sn
S
and discovered its characteristic surface Fermi-arcs and linear bulk band dispersions across the Weyl points. These results establish Co
Sn
S
as a magnetic Weyl semimetal that may serve as a platform for realizing phenomena such as chiral magnetic effects, unusually large anomalous Hall effect and quantum anomalous Hall effect.
Background and purpose
Besides a distinct spectrum of demyelinating syndromes, encephalitis was observed in patients with myelin oligodendrocyte glycoprotein antibodies (MOG‐abs).
Methods
The ...clinical records of 690 patients with idiopathic demyelinating diseases of the central nervous system seen in our center from June 2015 to December 2017 were retrospectively reviewed. All underwent serum aquaporin 4 antibody (AQP4‐ab) and MOG‐ab detection by cell‐based assays as a routine diagnostic approach. Patients with MOG‐abs or AQP4‐abs who had ever experienced an encephalitis‐like illness during the disease course were identified. Whether diagnoses of possible or definite autoimmune encephalitis could be reached with regard to these particular episodes of encephalitis was determined. The incidence and clinical features of encephalitis in anti‐MOG disease are described in detail and compared with those in anti‐AQP4 disease.
Results
Amongst the 690 patients, 87 were MOG‐ab‐positive whilst 140 were AQP4‐ab‐positive. 20.7% (18/87) of the MOG‐ab‐positive patients had typical presentations of encephalitis. Unique cortical lesions (72.2%, 13/18) were observed; fever (55.6%), intracranial hypertension (41.2%) and cerebrospinal fluid pleocytosis (64.7%) were common during MOG‐ab‐associated encephalitis. Sixteen of the 18 patients fulfilled the criteria of definite autoimmune encephalitis (specific disease with MOG‐ab) during encephalitis, and five patients overlapped with anti‐N‐methyl‐d‐aspartate‐receptor encephalitis (NMDARE). Only 3.6% (5/140) of the AQP4‐ab‐positive patients had encephalitis, and none overlapped with NMDARE. The Expanded Disability Status Scale scores and the Cerebral Functional System Scores at last follow‐up were lower in patients with MOG‐ab‐associated encephalitis than in those with AQP4‐ab‐associated encephalitis.
Conclusions
Encephalitis should be recognized as an important clinical component in anti‐MOG diseases.
The role of androgen and androgen receptor (AR) in breast carcinogenesis has long been a disputed issue. This report provides a mechanistic insight into how androgen and AR contributes to invasion ...and metastasis of breast cancer. We find that dihydrotestosterone (DHT) is able to induce the epithelial-to-mesenchymal transition in breast cancer cells in an AR-dependent/estrogen receptor-independent manner. This process is dependent on the demethylation activity of lysine-specific demethylase 1A (LSD1) by epigenetically regulating the target genes E-cadherin and vimentin. In vivo, DHT promotes metastasis in a nude mouse model, and AR and LSD1 are indispensable in this process. We establish that higher expression of nucleus AR to cytoplasm AR associated with worse prognostic outcomes in breast cancer patient samples. This study maps an 'androgen-AR/LSD1-target genes' pathway in breast carcinogenesis, implicating the importance of hormonal balance in women, and the potential clinical significance of serum androgen and AR in prediction of breast cancer and selection of breast cancer therapy.
Rejuvenation of metallic glasses, bringing them to higher-energy states, is of interest in improving their plasticity. The mechanisms of rejuvenation are poorly understood, and its limits remain ...unexplored. We use constrained loading in compression to impose substantial plastic flow on a zirconium-based bulk metallic glass. The maximum measured effects are that the hardness of the glass decreases by 36%, and its excess enthalpy (above the relaxed state) increases to 41% of the enthalpy of melting. Comparably high degrees of rejuvenation have been reported only on microscopic scales at the centre of shear bands confined to low volume fractions. This extreme rejuvenation of a bulk glass gives a state equivalent to that obtainable by quenching the liquid at ~10
K s
, many orders of magnitude faster than is possible for bulk specimens. The contrast with earlier results showing relaxation in similar tests under tension emphasizes the importance of hydrostatic stress.
Summary
Background
Tinea capitis is still common in developing countries, such as China. Its pathogen spectrum varies across regions and changes over time.
Objectives
This study aimed to clarify the ...current epidemiological characteristics and pathogen spectrum of tinea capitis in China.
Methods
A multicentre, prospective descriptive study involving 29 tertiary hospitals in China was conducted. From August 2019 to July 2020, 611 patients with tinea capitis were enrolled. Data concerning demography, risk factors and fungal tests were collected. When necessary, the pathogens were further identified by morphology or molecular sequencing in the central laboratory.
Results
Among all enrolled patients, 74·1% of the cases were in patients aged 2–8 years. The children with tinea capitis were mainly boys (56·2%) and were more likely than adults to have a history of animal contact (57·4% vs. 35·3%, P = 0·012) and zoophilic dermatophyte infection (73·5% vs. 47%). The adults were mainly female (83%) and were more likely than children to have anthropophilic agent infection (53% vs. 23·9%). The most common pathogen was zoophilic Microsporum canis (354, 65·2%), followed by anthropophilic Trichophyton violaceum (74, 13·6%). In contrast to the eastern, western and northeastern regions, where zoophilic M. canis predominated, anthropophilic T. violaceum predominated in central China (69%, P < 0·001), where the patients had the most tinea at other sites (20%) and dermatophytosis contact (26%) but the least animal contact (39%). Microsporum ferrugineum was the most common anthropophilic agent in the western area, especially in Xinjiang province.
Conclusions
Boys aged approximately 5 years were the most commonly affected group. Dermatologists are advised to pay more attention to the different transmission routes and pathogen spectra in different age groups from different regions.
What is already known about this topic?
Tinea capitis is an infection of the scalp and hair caused by dermatophytes and is still common in developing countries. Prepubertal children are mainly affected.
The pathogen spectrum of tinea capitis varies across different geographical areas and changes over time.
Nationwide prospective epidemiological surveys of tinea capitis in China are rare and out of date.
What does this study add?
This study provides data concerning the epidemiological characteristics and pathogen spectrum of tinea capitis in contemporary China.
Boys aged approximately 5 years were most commonly affected and were more likely than adults to have zoophilic dermatophyte infection.
The main pathogens of tinea capitis in China are zoophilic dermatophytes, mainly Microsporum canis. In contrast to the other regions, the predominant pathogens in central China are anthropophilic dermatophytes.
Plain language summary available online
Background
The expression of chronic rhinosinusitis (CRS) is multidimensional. Disease heterogeneity in patients with CRS remains poorly understood. This study aimed to identify endotypes of CRS ...using cluster analysis by integrating multidimensional characteristics and to explore their association with treatment outcomes.
Methods
A total of 28 clinical variables and 39 mucosal cellular and molecular variables were analyzed using principal component analysis. Cluster analysis was performed on 246 prospectively recruited Chinese CRS patients with at least 1‐year postoperative follow‐up. Difficult‐to‐treat CRS was characterized in each generated cluster.
Results
Seven subject clusters were identified. Cluster 1 (13.01%) was comparable to the classic well‐defined eosinophilic CRS with polyps, having severe disease and the highest proportion of difficult‐to‐treat CRS. Patients in cluster 2 (16.26%) and cluster 4 (13.82%) had relatively lower proportions of presence of polyps and presented mild inflammation with moderate proportions of difficult‐to‐treat cases. Subjects in cluster 2 were highly atopic. Cluster 3 (7.31%) and cluster 6 (21.14%) were characterized by severe or moderate neutrophilic inflammation, respectively, and with elevated levels of IL‐8 and high proportions of difficult‐to‐treat CRS. Cluster 5 (4.07%) was a unique group characterized by the highest levels of IL‐10 and lacked difficult‐to‐treat cases. Cluster 7 (24.39%) demonstrated the lowest symptom severity, a low proportion of difficult‐to‐treat CRS, and low inflammation load. Finally, we found that difficult‐to‐treat CRS was associated with distinct clinical features and biomarkers in the different clusters.
Conclusions
Distinct clinicopathobiologic clusters of CRS display differences in clinical response to treatments and characteristics of difficult‐to‐treat CRS.
Background
Delirium is common in elderly patients after surgery and is associated with poor outcomes. This study aimed to investigate the impact of intraoperative dexmedetomidine on the incidence of ...delirium in elderly patients undergoing major surgery.
Methods
This was a randomized double‐blind placebo‐controlled trial. Elderly patients (aged 60 years or more) scheduled to undergo major non‐cardiac surgery were randomized into two groups. Patients in the intervention group received a loading dose of dexmedetomidine 0·6 μg/kg 10 min before induction of anaesthesia followed by a continuous infusion (0·5 μg per kg per h) until 1 h before the end of surgery. Patients in the control group received volume‐matched normal saline in the same schedule. The primary outcome was the incidence of delirium during the first 5 days after surgery. Delirium was assessed with the Confusion Assessment Method (CAM) for non‐ventilated patients and CAM for the Intensive Care Unit for ventilated patients.
Results
In total, 309 patients who received dexmedetomidine and 310 control patients were included in the intention‐to‐treat analysis. The incidence of delirium within 5 days of surgery was lower with dexmedetomidine treatment: 5·5 per cent (17 of 309) versus 10·3 per cent (32 of 310) in the control group (relative risk (RR) 0·53, 95 per cent c.i. 0·30 to 0·94; P = 0·026). The overall incidence of complications at 30 days was also lower after dexmedetomidine (19·4 per cent (60 of 309) versus 26·1 per cent (81 of 310) for controls; RR 0·74, 0·55 to 0·99, P = 0·047).
Conclusion
Intraoperative dexmedetomidine halved the risk of delirium in the elderly after major non‐cardiac surgery. Registration number: ChiCTR‐IPR‐15007654 (
www.chictr.org.cn).
Antecedentes
El delirio después de la cirugía es frecuente en los pacientes de edad avanzada y se asocia con malos resultados. El objetivo de este estudio fue investigar el impacto de la administración intraoperatoria de dexmedetomidina en la incidencia de delirio en pacientes mayores sometidos a operaciones de cirugía mayor.
Métodos
Se trataba de un ensayo aleatorizado, doble ciego y controlado con placebo. Un total de 620 pacientes mayores (60 años o más) fueron programados para ser sometidos a intervenciones (no cardiacas) de cirugía mayor y se aleatorizaron a dos grupos. Los pacientes en el grupo de intervención recibieron una dosis de carga de dexmedetomidina (0,6 μg/kg, 10 minutos antes de la inducción anestésica) seguida de una infusión continua (0,5 μg/kg/h) hasta 1 h antes de la finalización de la cirugía. Los pacientes del grupo control recibieron el mismo volumen de suero salino siguiendo la misma pauta. El resultado principal era la incidencia de delirio durante los primeros 5 días postoperatorios. Para la valoración del delirio se utilizó el método para la evaluación de la confusión (Confusion Assessment Method, CAM) en pacientes no intubados y el CAM‐UCI para los pacientes intubados.
Resultados
En total, 309 pacientes que recibieron dexmedetomidina y 310 del grupo control se incluyeron en el análisis por intención de tratar. La incidencia de delirio durante los primeros 5 días tras la cirugía fue inferior en presencia de tratamiento con dexmedetomidina que en ausencia del mismo: 5,5% (17/309) versus 10,3% (32/310); riesgo relativo (RR) 0,53, i.c. del 95% 0,30‐0,94, P = 0,026. La incidencia global de complicaciones a los 30 días excluyendo el delirio también fue inferior en presencia que en ausencia de tratamiento con dexmedetomidina (19,4% (60/309) versus 26,1% (81/301), RR 0,74, i.c. del 95% 0,55‐0,99, P = 0,047).
Conclusión
La administración intraoperatoria de dexmedetomidina reduce la presencia de delirio en los pacientes mayores tras cirugía mayor no cardiaca.
In this RCT, intraoperative infusion of dexmedetomidine was found to reduce the rate of postoperative delirium and surgery‐related complications. The shortcomings of previous studies, such as study design and sample size, were amended, providing more robust evidence for clinical practice.
Halved the rate of delirium
MicroRNA-146a and Human Disease Li, L; Chen, X.-P; Li, Y.-J
Scandinavian journal of immunology,
April 2010, Letnik:
71, Številka:
4
Journal Article
Recenzirano
Odprti dostop
MicroRNAs (MiRNAs) belong to a class of small non-coding regulatory RNAs that act through repression of protein expression at post-transcriptional level and emerge to play important roles in many ...physiological and pathophysiological processes. MiR-146a is a miRNA supposed to regulate innate immune, inflammatory response and antiviral pathway negatively. In this review, we focus on the recent progress in functional role of miR-146a in innate immune, inflammatory response, virus infection and human diseases. Together, these findings indicate that manipulation of miR-146a expression may represent a potential new therapy for several human diseases. Potential use of miR-146a as a biomarker for disease diagnosis, prevention and treatment is also discussed.
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