非凋亡调节性细胞死亡基因对肺腺癌预后的预测价值及其生物学功能

目的探究非凋亡调节性细胞死亡基因(non-apoptotic regulatory cell death genes,NARCDs)预测肺腺癌预后的价值及其潜在生物学功能。方法我们下载癌症基因组图谱(The Cancer Genome Atla,TCGA)及基因表达综合(Gene Expression Omnibus,GEO)数据库中肺腺癌的转录组数据。使用R软件分析在肺腺癌组织和正常组织之间存在差异表达的NARCDs。采用单变量Cox分析和LASSO-Cox回归分析构建NARCDs预后模型。采用生存分析曲线、受试者工作特征曲线、单因素和多因素Cox回归分析评估NARCDs预后模型对肺腺癌预后的预测能力。采用GSVA、GO和KEGG分析NARCDs预后模型的功能富集情况。此外,我们分析了高、低NARCDs评分组间的肿瘤突变负担、肿瘤微环境、肿瘤免疫功能障碍与排斥(Tumor Immune Dysfunction and Exclusion,TIDE)评分和化疗药物敏感性的差异。最后,使用STRING和Cytoscape软件构建NARCDs与免疫相关基因的蛋白-蛋白相互作用网络。结果我们确定了34个与预后相关的差异表达NARCDs,其中16个基因(ATIC、AURKA、CA9、ITGB4、DDIT4、CDK5R1、CAV1、RRM2、GAPDH、SRXN1、NLRC4、GLS2、ADRB2、CX3CL1、GDF15和ADRA1A)被用于构建NARCDs预后模型。NARCDs风险评分是肺腺癌的独立预后因素(P<0.001)。功能分析显示:高NARCDs评分组与低NARCDs评分组间在错配修复、p53信号通路和细胞周期方面存在显著差异(P<0.05)。低NARCD评分组的肿瘤突变负荷较低,免疫评分及TIDE评分较高,对药物的敏感性较低(P<0.05)。此外,蛋白-蛋白相互作用网络的10个关键基因(CXCL5、TLR4、JUN、IL6、CCL2、CXCL2、ILA、IFNG、IL33和GAPDH)均为免疫相关基因。结论基于16个基因构建的NARCDs预后模型是肺腺癌的独立预后因素,其能有效预测患者预后,并为临床治疗提供帮助。

Faden术在矫正非屈光调节性内斜视中作用分析

目的探讨Faden术在非屈光调节性内斜视矫正中的作用。方法取12例非屈光调节性内斜视，AC／A值〉7，远近斜视角相差在15n以上，根据斜视度行双内直肌Faden术或双内直肌后退联合Faden术。结果术后10例患者视远和视近时基本正位，1例视近仍残余〈＋15。内斜视，1例视远过矫。结论Faden术可有效矫正非屈光调节性内斜视的斜度。

调节性非编码RNA在先天性巨结肠中的研究进展

调节性非编码RNA是具有调节作用的一类非编码RNA，在人神经系统的发育及可塑性中发挥重要作用，且与人神经系统相关疾病的发病机制密切相关。先天性巨结肠（HD）是小儿最常见的消化道畸形，目前发病原因不清，普遍认为是肠神经系统（ENS）在胚胎时期的异常发育引起的；随着人们对调节性非编码RNA在人神经系统发育中研究的不断深入，发现调节性非编码RNA与HD的发病存在密切关系，为HD发病机制的研究提供了参考。本研究对调节性非编码RNA在HD发病机制中的研究进展进行综述，探讨调节性非编码RNA在HD中的作用。

Online frequency and power regulation scheme of magnetic coupled resonant wireless power transfer

In order to address the issues that the magnetic coupled resonant wireless power transfer （MCR-WPT） system is sensitive to the resonant frequency and that transmission power is difficult to control with the non-resistive load in the MCR-WPT, a single-side regulation scheme for frequency and transmission power online is proposed, which is based on the inherent constraint relationships the among system parameters in the primary side. Thus, the communication between the primary side and the secondary side is avoided. First, the transfer models of resistance-capacitance load and resistance- inductance load are established, respectively. Next, the relationship between the input voltage phasor and the input current phasor is used to recognize the load property and value. Then, the coaxial rotation of the stepper motor and the rotating vacuum variable capacitor is conducted to unify resonant frequency both in the primary side and the secondary side. Finally, the regulations of both frequency and amplitude of input voltage are made to guarantee transmission power under a new resonant frequency point the same as the one when the only pure resistance part of load is accessed under the former resonant frequency point. Both simulation and experimental results indicate that the proposed regulation scheme can track remnant frequency and maintain transmission power constant.

Processing Approach of Non-linear Adjustment Models in the Space of Non-linear Models

This paper investigates the mathematic features of non-linear models and discusses the processing way of non-linear factors which contributes to the non-linearity of a non-linear model. On the basis of the error definition,this paper puts forward a new adjustment criterion, SGPE.Last,this paper investigates the solution of a non-linear regression model in the non-linear model space and makes the comparison between the estimated values in non-linear model space and those in linear model space.

INVESTIGATION OF REGULATORY T CELLS IN PATIENTS WITH NON-SMALL CELL LUNG CANCER

Objective To evaluate the prevalence of CD4 ^＋ CD25^high regulatory T cells （ Treg cells） in the peripheral blood mononuclear cells （PBMC） and tumor-infiltrating lymphocytes （TIL） of patients with non-small cell lung cancer （NSCLC） and to investigate immunosuppression to the progression of cancer. Methods Peripheral blood and tumor tissues were collected from 20 patients with NSCLC at the time of surgery. None of the patients received surgery, radiotherapy, chemotherapy, or other medical interventions before this study. Cancer stages of the patients were Ⅰ-Ⅲ A. Venous blood samples were obtained from 20 health donors. PBMC were isolated from blood samples by differential centrifugation over Ficoll-Hypaque. TILs were isolated from tumors by differential centrifugation over Ficoll-Hypaque and Percoll. Percentage of CD4^＋ CD25^highTr/CD4＋T in PBMC and TIL was assessed by the flow cytometry. Results The percentage of CD4^ ＋ CD25high Tr/ CD4 ^＋T in PBMC [ （4. 87 ± 1.22 ） % ] of NSCLC patients was significantly higher than that in healthy donors [ （ 2.36 ± 0. 72 ） % ] （ P 〈 0.01 ）. The percentage of CD4^＋ CD25^highTr/ CD4^＋ T in PBMC [ （5.40 ± 1.20） % ] of NSCLC patients in stage Ⅱ-Ⅲ A was significantly higher than that in stage Ⅰ [ （3. 87 ± 0. 22 ） % ] （ P 〈 0. 01 ）. The percentage of CD4 ＋ CD25hiShTr/ CD4 ＋ T in TIL[ （ 8. 66 ±0. 76） % ] of NSCLC patients in stage Ⅱ-Ⅲ A was significantly higher than that in stage Ⅰ [ （ 7. 04 ± 0. 80） % ] （ P 〈 0. 01 ）. Conclusion The prevalence of CD4 ^＋ CD25^highTreg cells in PBMC and TIL of NSCLC patients was significantly higher than that in healthy donors. These Treg cells may be preventing appropriate antitumor immune responses. The population of CD4^ ＋ CD25^highTreg cells in PBMC and TILs of NSCLC patients with Ⅱ-Ⅲ A stage was significantly higher than that of NSCLC patients with Ⅰ stage. These Treg cells may facilitate development of tumors.

Optimization of air quantity regulation in mine ventilation networks using the improved differential evolution algorithm and critical path method

In mine ventilation networks, the reasonable airflow distribution is very important for the production safety and economy. Three basic problems of the natural, full-controlled and semi-controlled splitting were reviewed in the paper. Aiming at the high difficulty semi-controlled splitting problem, the general nonlinear multi-objectives optimization mathematical model with constraints was established based on the theory of mine ventilation networks. A new algorithm, which combined the improved differential evaluation and the critical path method （CPM） based on the multivariable separate solution strategy, was put forward to search for the global optimal solution more efficiently. In each step of evolution, the feasible solutions of air quantity distribution are firstly produced by the improved differential evolu- tion algorithm, and then the optimal solutions of regulator pressure drop are obtained by the CPM. Through finite steps iterations, the optimal solution can be given. In this new algorithm, the population of feasible solutions were sorted and grouped for enhancing the global search ability and the individuals in general group were randomly initialized for keeping diversity. Meanwhile, the individual neighbor- hood in the fine group which may be closely to the optimal solutions were searched locally and slightly for achieving a balance between global searching and local searching, thus improving the convergence rate. The computer program was developed based on this method. Finally, the two ventilation networks with single-fan and multi-fans were solved. The results show that this algorithm has advantages of high effectiveness, fast convergence, good robustness and flexibility. This computer program could be used to solve lar^e-scale ~eneralized ventilation networks o^timization problem in the future.

A Parameter Determination Method of Distribution Voltage Regulators Considering Tap Change and Voltage Profile

This paper proposes a parameter determination method of distribution voltage regulators load ratio control transformers （LRT） and step voltage regulators （SVR） considering the tap change and voltage profile. The method takes two procedures in order to simplify the optimization problem and to reduce calculation time. One is to simultaneously determine the control parameters of LRT and SVR minimizing voltage violations and voltage variations. The algorithm is based on particle swarm optimization （PSO）, which is one of non-linear optimization methods by using a concept of swarm intelligence. Another is to determine the dead-band width of LRT and SVR on the basis of bi-evaluation of tap change and voltage margin. The concept of a Pareto optimal solution is used for the decision of the best dead-band width. As the results of numerical simulations using distribution network model, the validity of the proposed method has been affirmed.

Neuromodulation for tinnitus treatment:an overview of invasive and non-invasive techniques

Tinnitus is defined as a perception of sound without any external sound source.Chronic tinnitus is a frequent condition that can affect the quality of life.So far,no causal cure for tinnitus has been documented,and most pharmacologic and psychosomatic treatment modalities aim to diminish tinnitus’impact on the quality of life.Neuromodulation,a novel therapeutic modality,which aims at alternating nerve activity through a targeted delivery of a stimulus,has emerged as a potential option in tinnitus treatment.This review provides a brief overview of the current neuromodulation techniques as tinnitus treatment options.The main intention is to provide updated knowledge especially for medical professionals counselling tinnitus patients in this emerging field of medicine.Non-invasive methods such as repetitive transcranial magnetic stimulation,transcranial electrical stimulation,neurofeedback,and transcutaneous vagus nerve stimulation were included,as well as invasive methods such as implanted vagus nerve stimulation and invasive brain stimulation.Some of these neuromodulation techniques revealed promising results;nevertheless,further research is needed,especially regarding the pathophysiological principle as to how these neuromodulation techniques work and what neuronal change they induce.Various studies suggest that individually different brain states and networks are involved in the generation and perception of tinnitus.Therefore,in the future,individually tailored neuromodulation strategies could be a promising approach in tinnitus treatment for achieving a more substantial and longer lasting improvement of complaints.

Canonical transient receptor potential 4 and its small molecule modulators

Canonical transient receptor potential 4(TRPC4) forms non-selective cation channels that contribute to phospholipase C-dependent Ca2+ entry into cells following stimulation of G protein coupled receptors and receptor tyrosine kinases.Moreover,the channels are regulated by pertussis toxin-sensitive Gi/o proteins,lipids,and various other signaling mechanisms.TRPC4-containing channels participate in the regulation of a variety of physiological functions,including excitability of both gastrointestinal smooth muscles and brain neurons.This review is to present recent advances in the understanding of physiology and development of small molecular modulators of TRPC4 channels.

Impaired function of the suprachiasmatic nucleus rescues the loss of body temperature homeostasis caused by time-restricted feeding

The suprachiasmatic nucleus(SCN)is the master circadian pacemaker that drives body temperature rhythm.Time-restricted feeding(TRF)has potential as a preventative or therapeutic approach against many diseases.The potential side effects of TRF remain unknown.Here we show that daily 4-h TRF treatment in mice can severely impair body temperature homeostasis and can result in lethality.Nearly half of the mice died at 21℃,and all mice died at 18℃during 4-h TRF.This effect was modulated by the circadian clock and was associated with severe hypothermia due to loss of body temperature homeostasis.Remarkably,disrupting the circadian clock by SCN lesions or constant light rescued lethality during TRF.Analysis of circadian gene expression in the dorsomedial hypothalamus(DMH)demonstrated that TRF reprograms rhythmic transcriptome in DMH and suppresses expression of genes,such as Ccr5 and Calcrl,which are involved in thermoregulation.Together,our results demonstrated a potent effect of TRF on body temperature homeostasis and the role of SCN function in this process.Our results further suggested that circadian arrhythmicity can have potential beneficial effects under certain stress conditions.

AN ALTERNATIVE APPROACH TO GLOBAL ROBUST OUTPUT REGULATION OF OUTPUT FEEDBACK SYSTEMS

The global robust output regulation problem of the output feedback systems has been extensively studied under various assumptions of the complexity and uncertainty. All these approaches boil down to a stabilization problem of a so-called augmented extended system. This paper will describe an alternative approach which converts the original problem into a stabilization problem of a so-called extended augmented system. As the extended augmented system is somewhat simpler than the augmented extended system, this alternative approach is also simpler than the first approach.

Tuning of Sampled-Data ADRC for Nonlinear Uncertain Systems

This paper concerns with the parameters tuning of active disturbance rejection control(ADRC) for a class of nonlinear systems with sampling rate not fast enough. The theoretical results show the quantitative relationship between the sampling rate, the parameters of ADRC, the size of uncertainties in system and the properties of the closed-loop system. Furthermore, the capability of the sampled-data ADRC under given sampling rate is quantitatively discussed.