巨噬细胞相关基因与非小细胞肺癌预后和肿瘤微环境的分析

非小细胞肺癌(non-small cell lung cancer,NSCLC)是一种高发病率和高死亡率的疾病,其预后和药物治疗效果存在个体化差异。因此,了解肺癌发生和发展的分子机制可以有效提高早期诊断和治疗,改善患者预后。巨噬细胞具有高度可塑性和异质性,是肿瘤微环境(tumor microenvironment,TME)中发挥抗肿瘤作用的关键细胞之一,在肿瘤发生发展过程中起着复杂的作用。为了阐明NSCLC中肿瘤相关巨噬细胞(tumor-associated macrophages,TAMs)相关基因在肺癌中的发生机制,本研究采用转录组测序、单因素COX回归、LASSO回归、多因素COX回归分析方法,筛选出与预后最相关的11个基因(FCRLA、LDHA、LMOD3、MAP3K8、NT5E、PDGFB、S100P、SFXN1、TDRD1、TFAP2A、TUBB6)。计算风险评分(risk score,RS),根据RS中位数将所有样本分为高风险组和低风险组,并采用CIBERSORT反卷积算法验证RS及11个基因与巨噬细胞的相关性。上述结果表明,本研究所建立的风险评分可用于非小细胞肺癌患者预后预测,还可评估患者的免疫浸润状态,为后续肿瘤免疫治疗及基因靶向治疗提供参考。

Enhanced anticancer effect of doxorubicin by TPGS-coated liposomes with Bcl-2 siRNA-corona for dual suppression of drug resistance

Multiple drug resistance(MDR)is a tough problem in developing hepatocellular carcinoma(HCC)therapy.Here,we developed TPGS-coated cationic liposomes with Bcl-2 siRNA corona to load doxorubicin(Dox)i.e.,Bcl-2 siRNA/Dox-TPGS-LPs,to enhance anticancer effect of Dox in HCC-MDR.TPGS i.e.,d-α-tocopheryl polyethylene glycol 1000 succinate,inhibited Pglycoprotein(P-gp)efflux pump and Bcl-2 siRNA suppressed anti-apoptotic Bcl-2 protein.The Bcl-2 siRNA loaded in the liposomal corona was observed under transmission electron microscopy.The stability and hemolysis evaluation demonstrated Bcl-2 siRNA/Dox-TPGSLPs had good biocompatibility and siRNA-corona could protect the liposomal core to avoid the attachment of fetal bovine serum.In drug-resistant cells,TPGS effectively prolonged intracellular Dox retention time and siRNA-corona did improve the internalization of Dox from liposomes.In vitro and in vivo anticancer effect of this dual-functional nanostructure was examined in HCC-MDR Bel7402/5-FU tumor model.MTT assay confirmed the IC50 value of Dox was 20–50 fold higher in Bel7402/5-FU MDR cells than that in sensitive Bel7402 cells.Bcl-2 siRNA corona successfully entered the cytosol of Bel7402/5-FU MDR cells to downregulate Bcl-2 protein levels in vitro and in vivo.Bcl-2 siRNA/Dox-TPGS-LPs showed superior to TPGS-(or siRNA-)linked Dox liposomes in cell apoptosis and cytotoxicity assay in Bel7402/5-FU MDR cells,and 7-fold greater effect than free Dox in tumor growth inhibition of Bel7402/5-FU xenograft nude mice.In conclusion,TPGS-coated cationic liposomes with Bcl-2 siRNA corona had the capacity to inhibit MDR dual-pathways and subsequently improved the anti-tumor activity of the chemotherapeutic agent co-delivered to a level that cannot be achieved by inhibiting a MDR single way.

Development of a biomechanical model for dynamic occlusal stress analysis

The use of traditional finite element method(FEM)in occlusal stress analysis is limited due to the complexity of musculature simulation.The present purpose was to develop a displacement boundary condition(DBC)-FEM,which evaded the muscle factor,to predict the dynamic occlusal stress.The geometry of the DBC-FEM was developed based on the scanned plastic casts obtained from a volunteer.The electrognathographic and video recorded jaw positional messages were adopted to analyze the dynamic occlusal stress.The volunteer exhibited asymmetrical lateral movements,so that the occlusal stress was further analyzed by using the parameters obtained from the right-side eccentric movement,which was 6.9 mm long,in the stress task of the left-side eccentric movement,which was 4.1 mm long.Further,virtual occlusion modification was performed by using the carving tool software aiming to improve the occlusal morphology at the loading sites.T-Scan Occlusal System was used as a control of the in vivo detection for the location and strength of the occlusal contacts.Data obtained from the calculation using the present developed DBC-FEM indicated that the stress distribution on the dental surface changed dynamically with the occlusal contacts.Consistent with the T-Scan recordings,the right-side molars always showed contacts and higher levels of stress.Replacing the leftside eccentric movement trace by the right-side one enhanced the simulated stress on the right-side molars while modification of the right-side molars reduced the simulated stress.The present DBC-FEM offers a creative approach for pragmatic occlusion stress prediction.

The Combined Application of WTP and WTA in Contingent Valuation Methods

The In most contingent valuation (CV) studies, WTP (Willingness to pay) and WTA (Willingness to accept) were often used separately, so protesting or no response or even babbling answers are increasing, and the debate persists over the reliability of CV in economic policy analysis. In order to improve the reliability of CV, WTP and WTA is used syn-chronously to estimate the restoration cost of Maqu grassland ecosystem. Data were partly from questionnaire survey, and partly from interviews and authorities. Before conclusions were derived, we assumed these data that came from interviews and authorities were right. The main result is: If we assumed that the degraded grassland of Maqu needs 10 years to be restored, and divided the restoring period into two stages, then the restoration cost was 0.85 × 108 RMB per year in former 4 years, 0.022 × 108 RMB per year in latter 6 years. The total cost of Maqu grassland restoration was 3.62 × 108 RMB. For all the costs of restoration, WTA occupied 94% and WTP only occupied 6%, suggesting that local grassland degradation was mainly caused by overgrazing and that the overloading livestock must be eliminated in order to achieve restoration successfully. Our research also showed that combining WTP and WTA in contingent valuation is very useful in estimating the cost of environmental improvement projects. Of course, whether these results are right or not, further researches are needed in the future, especially for the actual number of livestock in Maqu grassland.

Advances in Acupuncture and its Associated Therapies for the Prevention and Treatment of Obesity Type 2 Diabetes Mellitus

Obesity type 2 diabetes mellitus is a common metabolic disease in clinical practice,and its prevalence is increasing rapidly with the aging of the population and changes in lifestyle.Acupuncture,as a distinctive therapy,has its unique advantages in the treatment of obesity type 2 diabetes and has an irreplaceable role in a variety of treatment methods.The author organized the literature on acupuncture and its related therapies to prevent and treat obesity type 2 diabetes in recent years and found that acupuncture and its associated therapies to prevent and treat obesity type 2 diabetes mainly include:simple acupuncture,electroacupuncture,acupoint catgut embedding therapy,auricular-plaster therapy and other treatments,all of which can safely and effectively improve clinical symptoms,acupuncture and its related therapies to treat obesity type 2 diabetes has a broad prospect,worthy of further clinical promotion.

On the Treatment of Insomnia with Fang’s Scalp Acupuncture Based on the Therapy of “Regulating Mental Activities and Smoothing the Liver”

As a common clinical disease,insomnia was usually treated with anti-psychotic or sedativehypnotic drugs in Western medicine,which showed a fast efficacy,as well as easy drug tolerance and side effects.In traditional Chinese medicine,the basic and key pathogenesis of insomnia are believed to be“the restlessness of the mind”,as well as“the absence of the mind”;and the treatment mainly focus on“regulating mental activities and smoothing the liver”.By combining the theoretical basis and characteristics of Fang’s scalp acupuncture,this paper aims to explain the advantages of Fang’s scalp acupuncture in the treatment of insomnia,and provide new ideas and methods for its clinical treatment.

An investigation of long-term outcome of rabbit anti-thymocyte globulin and cyclosporine therapy for pediatric severe aplastic anemia

Children with severe aplastic anemia(SAA)face heterogeneous prognoses after immunosuppressive therapy(IST).There are few models that can predict the long-term outcomes of IST for these patients.The objective of this paper is to develop a more effective prediction model for SAA prognosis based on clinical electronic medical records from 203 children with newly diagnosed SAA.In the early stage,a novel model for long-term outcomes of SAA patients with IST was developed using machine-learning techniques.Among the indicators related to long-term efficacy,white blood cell count,lymphocyte count,absolute reticulocyte count,lymphocyte ratio in bone-marrow smears,C-reactive protein,and the level of IL-6,IL-8 and vitamin B12 in the early stage are strongly correlated with long-term efficacy(P<.05).Taken together,we analyzed the long-term outcomes of rabbit antithymocyte globulin and cyclosporine therapy for children with SAA through machine-learning techniques,which may shorten the observation period of therapeutic effects and reduce treatment costs and time.

利用Tet-On系统敲低PRDM5对BEAS-2B细胞增殖的影响

[目的]探讨利用dox诱导的Tet-On调控系统敲低PRDM5基因对人正常支气管上皮细胞BEAS-2B增殖的影响。[方法]构建敲低PRDM5基因的pLKO-Tet-On-PRDM5-shRNA慢病毒质粒,包装生产慢病毒并转染BEAS-2B细胞,以相同条件制备转染pLKO-Tet-On-control-shRNA的BEAS-2B细胞作为对照。WesternBlot法检测PRDM5蛋白的表达水平;MTT实验观察细胞增殖情况;平板克隆形成实验检测细胞增殖能力;流式细胞术检测细胞凋亡水平。[结果]在合适剂量的dox诱导下(0.5μg/mL),敲低组细胞中PRDM5蛋白表达明显低于对照组(P<0.05);各时间点OD值高于对照组(P<0.05);克隆形成数大于对照组(P<0.01);凋亡率低于对照组(P<0.01)。[结论]成功构建出Tet-On系统调控敲低PRDM5的BEAS-2B细胞系。PRDM5基因敲低可促进BEAS-2B细胞增殖并且抑制其凋亡。