Identifying dysfunctional miRNA-mRNA regulatory modules by inverse activation,cofunction, and high interconnection of target genes: A case study of glioblastoma

Background

Accumulating evidence demonstrates that complex diseases may arise from cooperative effects of multiple dysfunctional miRNAs. Thus, identifying abnormal functions cooperatively regulated by multiple miRNAs is useful for understanding the pathogenesis of complex diseases.

Methods

In this study, we proposed a multistep method to identify dysfunctional miRNA-mRNA regulatory modules (dMiMRMs) in a specific disease, in which a group of miRNAs cooperatively regulate a group of target genes involved in a specific function. We identified dysfunctional miRNAs, which were differentially expressed and inversely regulated most of their target genes, by integrating paired miRNA and mRNA expression profiles and miRNA target information. Then, we identified cooperative functional units, in each of which a pair of miRNAs cooperatively repressed function-enriched and highly interconnected target genes. Finally, the cooperative functional units were assembled into dMiMRMs.

Results

We applied our method to glioblastoma (GBM) and identified GBM-associated dMiMRMs at the population, subtype, and individual levels. We identified 5 common dMiMRMs using all GBM samples, 3 of which were associated with the prognosis in patients with GBM and were better predictors of prognosis than were miRNAs or mRNAs alone. By applying our approach to GBM subtypes, we found consistent dMiMRMs across GBM subtypes, and some subtype-specific dMiMRMs were observed. Furthermore, personalized dMiMRMs were identified, suggesting significant individual differences in different patients with GBM.

Conclusions

Our method provides the capability to identify miRNA-mediated dysfunctional mechanisms underlying complex diseases.     

中性粒细胞异常增殖相关的BCR/ABL-慢性白血病的临床特征

目的:探讨与中性粒细胞异常增殖相关的BCR/ABL-慢性白血病的临床特征.方法:报告3例不同类型与中性粒细胞异常增殖相关的BCR/ABL-慢性白血病并结合文献进行讨论.结果:3例均为老年男性,表现为以中性粒细胞为主的白细胞异常增多、BCR/ABL融合基因阴性.例1诊断为慢性中性粒细胞白血病(CNL),脾大,外周血以成熟中性粒细胞增高为特征,胞浆内中毒颗粒易见,无明显病态造血,中性粒细胞碱性磷酸酶(NAP)染色强阳性,骨髓粒系增生明显活跃.例2诊断为不典型慢性髓细胞白血病(aCML),血涂片示不成熟粒细胞比例增高伴粒系病态造血,尤其核染色质异常浓聚更为明显,骨髓象表现为髓系增生和病态造血,原始细胞轻度增多.例3诊断为慢性粒单核细胞白血病(CMML),外周血成熟单核细胞数量和比例异常偏高,粒系病态如核分叶过多、环状核和假性Pelger-Huet畸形等易见,骨髓髓系增生明显活跃伴病态造血,无原始细胞增多.结论:中性粒细胞异常增殖相关的BCR/ABL-慢性白血病较为少见,易于误诊,细胞形态学特征是诊断BCR/ABL-慢性白血病的基础.临床表现、多种实验室检查结果尤其是分子生物学等有助于正确诊断这类疾病.     

动物辅助疗法在康复护理中应用的研究进展

对动物辅助疗法的概念、发展、资质要求、干预方式、应用领域及在临床康复护理中的应用效果等方面进行综述,旨在为我国开展动物辅助疗法的护理干预提供借鉴和参考。     

Application value of coaxial puncture needle (technique) in ultrasound-guided puncture biopsy of peripheral pulmonary masses

This study aims to investigate the effect of ultrasound (US)-guided coaxial puncture needle in puncture biopsy of peripheral pulmonary masses. In this retrospective analysis, 157 patients who underwent US-guided percutaneous lung biopsy in our hospital were divided into a coaxial biopsy group and a conventional biopsy group (the control group) according to the puncture tools involved, with 73 and 84 patients, respectively. The average puncture time, number of sampling, sampling satisfaction rate, puncture success rate and complication rate between the 2 groups were compared and discussed in detail. One hundred fifty-seven patients underwent puncture biopsy, and 145 patients finally obtained definitive pathological results. The overall puncture success rate was 92.4% ([145/157]; with a puncture success rate of 97.3% [71/73] from the coaxial biopsy group and a puncture success rate of 88.1% [74/84] from the conventional biopsy group (P < .05). For peripheral pulmonary masses ≤3 cm, the average puncture time in the coaxial biopsy group was shorter than that in the conventional biopsy group, and the number of sampling, sampling satisfaction rate and puncture success rate were significantly higher than those in the conventional biopsy group (P < .05). There was no significant difference in the complication rate between the 2 groups (P > .05). For peripheral pulmonary masses >3 cm, the average puncture time in the coaxial biopsy group was still shorter than that in the conventional biopsy group (P < .05). The differences between the 2 groups in the number of sampling, satisfaction rate of the sampling, the success rate of puncture and the incidence of complications were not significant (P > .05). US guided coaxial puncture biopsy could save puncture time, increase the number of sampling, and improve the satisfaction rate of sampling and the success rate of puncture (especially for small lesions) by establishing a biopsy channel on the basis of the coaxial needle sheath. It provided reliable information for the diagnosis, differential diagnosis and individualized accurate treatment of lesions as well.     

Effects of Boride Orientation and Si Content on High-Temperature Oxidation Resistance of Directionally Solidified Fe–B Alloys

In this work, the as-cast directionally solidified (DS) Fe–B alloys with various Si contents and different boride orientation were designed and fabricated, and the as-cast microstructures and static oxidation behaviors of the DS Fe–B alloys were investigated extensively. The as-cast microstructure of the DS Fe–B alloys consists of the well-oriented Fe₂B columnar grains and α-Fe, which are strongly refined by Si addition. The oxidation interface of the scales in the DS Fe–B alloy with 3.50 wt.% Si demonstrates an obvious saw-tooth shaped structure and is embedded into the alternating distributed columnar layer structures of the DS Fe–B alloy with oriented Fe₂B and α-Fe matrix, which is beneficial to improve the anti-peeling performance of the oxide film compared with lower amounts of Si addition in DS Fe–B alloys with oriented Fe₂B [002] orientation parallel to the oxidation direction (i.e., oxidation diffusion direction, labeled as Fe₂B_// sample). In the DS Fe–B alloys with oriented Fe₂B [002] orientation vertical to the oxidation direction (i.e., labeled as Fe₂B_⊥ sample), due to the blocking and barrier effect of laminated-structure boride, Si is mainly enriched in the lower part of the oxide film to form a dense SiO₂ thin layer adhered to layered boride. As a result, the internal SiO₂ thin layer plays an obstructed and shielded role in oxidation of the substrate, which hinders the further internal diffusion of oxygen ions and improves the anti-oxidation performance of the Fe₂B_⊥ sample, making the average anti-oxidation performance better than that of the Fe₂B_// sample.     

Physicochemical Properties of Water-Based Copolymer and Zeolite Composite Sustained-Release Membrane Materials

A nitrogen fertilizer slow-release membrane was proposed using polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), epoxy resin, and zeolite as raw materials. The effects of the water-based copolymer (PVA:PVP) solution ratio A (A₁–A₄) and zeolite amount B (B₁–B₄) on the water absorption rate (XS), water permeability (TS), fertilizer permeability (TF), tensile strength (KL), elongation at break (DSL), and viscosity (ND) of the membrane were explored using the swelling method, a self-made device, and a universal testing machine. The optimal combination of the water-based copolymer and zeolite amount was determined by the coefficient-of-variation method. The results show that the effects of the decrease in A on KL and the increase in B on KL and DSL are promoted first and then inhibited. DSL and ND showed a negative response to the A decrease, whereas XS, TS, and TF showed a positive response. The effect of increasing B on ND, TS, and TF showed a zigzag fluctuation. In the condition of A₁–A₃, XS showed a negative response to the B increase, whereas in the condition of A₄, XS was promoted first and then inhibited. Adding PVP and zeolite caused the hydroxyl stretching vibration peak of PVA at 3300 cm⁻¹ to widen; the former caused the vibration peak to move to low frequencies, and the latter caused it to move to high frequencies. The XRD pattern shows that the highest peak of zeolite is located at 2θ = 7.18° and the crystallization peak of the composite membrane increases with the rise in the proportion of zeolite. Adding PVP made the surface of the membrane smooth and flat, and adding a small amount of zeolite improved the mechanical properties of the membrane and exhibited good compatibility with water-based copolymers. In the evaluation model of the physicochemical properties of sustained-release membrane materials, the weight of all indicators was in the following order: TF > ND > TS > KL > XL > DSL. The optimal membrane material for comprehensive performance was determined to be A₂B₃.     

Inter-Fighting between Influenza A Virus NS1 and β-TrCP: A Novel Mechanism of Anti-Influenza Virus

Influenza A virus (IAV) prevents innate immune signaling during infection. In our previous study, the production of pro-inflammatory cytokines was associated with Cullin-1 RING ligase (CRL1), which was related to NF-κB activation. However, the underlying mechanism is unclear. Here, an E3 ligase, β-transducin repeat-containing protein (β-TrCP), was significantly downregulated during IAV infection. Co-IP analysis revealed that non-structural 1 protein (NS1) interacts with β-TrCP. With co-transfection, an increase in NS1 expression led to a reduction in β-TrCP expression, affecting the level of IκBα and then resulting in repression of the activation of the NF-κB pathway during IAV infection. In addition, β-TrCP targets the viral NS1 protein and significantly reduces the replication level of influenza virus. Our results provide a novel mechanism for influenza to modulate its immune response during infection, and β-TrCP may be a novel target for influenza virus antagonism.     

Prospects of Probiotic Adjuvant Drugs in Clinical Treatment

In modern society, where new diseases and viruses are constantly emerging, drugs are still the most important means of resistance. However, adverse effects and diminished efficacy remain the leading cause of treatment failure and a major determinant of impaired health-related quality of life for patients. Clinical studies have shown that the disturbance of the gut microbial structure plays a crucial role in the toxic and side effects of drugs. It is well known that probiotics have the ability to maintain the balance of intestinal microecology, which implies their potential as an adjunct to prevent and alleviate the adverse reactions of drugs and to make medicines play a better role. In addition, in the past decade, probiotics have been found to have excellent prevention and alleviation effects in drug toxicity side effects, such as liver injury. In this review, we summarize the development history of probiotics, discuss the impact on drug side effects of probiotics, and propose the underlying mechanisms. Probiotics will be a new star in the world of complementary medicine.