养练人格 高视阔步——由命题作文《奔》《酷》《跑》谈作文立“意”

笔者在参与某作文大赛的参赛作品评审时，发现一些参赛的同学力图创新．殚精竭虑地编制了产品说明书、病历报告、实验报告、数学证明、新闻报道等文体新颖、形式多样的文章：另有一些参赛的同学着力锤炼词句，捏造生词生语，大量运用修辞手法．煞费苦心地写就了语言奢华绮丽的作品。这些竞赛作文大多是尝试用文体和形式创新，采用标准和套路等有为之法来取胜，结果弱化了思想内涵．导致文章内容浅俗空洞、语言脱离文意。

释“酷”

“酷”是近年来使用频率极高的一个时尚词语。语料分析与公众诠释、社会调查相互参证 ,可知“酷”有“冷淡”、“严肃”、“漂亮”、“有品位”、“新潮前卫”、“有个性”、“另类”、“阳刚”、“潇洒”等义项。“酷”主要用来形容对人或事物的印象 ,带有主观评价性质 ;它借自英语流行词cool,但借入后词义更为丰富。

酷

“哇,好酷啊!”“哇噻,酷毙了!”今天,中学生言必谈酷:头染黄发,“野火烧不尽”,这是酷;身着奇装,如“北方的狼”,那叫酷;体刺纹身,如“动物世界”,也称酷;故作冷静,“沉默是金”,也夸酷;特立独行,“来也匆匆,去也匆匆”,还说酷。怪异是酷,沉默是酷,叛逆是酷。酷是美感,酷是魅力,酷是形象。

酷班众生相

在我们酷酷的四（1）班这个大家庭里，有着一些与众不同的牛人，本文就让他们彻底露露脸吧。 一、神秘忍者——杜光煜。此人行如风、去无踪，眼睛里总是有一股剑光二样的杀气，可人呢，却整天咧着个大嘴巴坏笑，总有一种神秘兮兮的感觉，让人捉摸不透、毛骨悚然、心惊胆颤。

酷酷猫（续五）

酷酷猫决定跳槽的目标是戴伟。事情是这样的：

故事串串香--酷酷猫（续二）

5．猫的感受 这天，酷儿正在学校的垃圾桶里找食呢。“啪!”酷儿一下子被震醒了。原来是几个小调皮一脚把垃圾桶踢飞了。酷儿一看，呀!是班上的余世、苏廷、杨扬和那个冒充自己的假酷儿!酷儿本来不想去计较，可现在这些人把他喜欢吃的东西——香喷喷的北京烤鸭、软绵绵的年糕等踢得到处都是！

酷酷猫

酷儿实在忍无可忍了，在又一次和外婆的争吵中，他实现了自己曾经扬言当流浪儿的誓言。

酷温暖:一点点糖,一点点甜

无数栗子在大锅里被搅拌着．炒栗子的师傅拿起一碗糖水．一点一点均匀地洒下去。不知怎的．我的心中竟有一种莫名的感动……

酷玩搜罗

玉米可以做抱枕，面包也是拖鞋……咦？小COOL龙在说些什么呀？嘻嘻，看看下面的新奇东东你就知道啦！绝对让你大开眼界！

你确定要这样赚钱？《酷划》

如何通过你的手机赚钱？想必这是很多人都曾思考过的问题。面对这样一个用户刚需，不少头脑灵活的创业者自然也已蠢蠢欲动。只要解锁屏幕就能赚钱，这是《酷划》的创意。不过，这个钱可不好赚。

李宇春帅气亮相发布会 好身材被赞秒杀车模

5月6日晚。李宇春亮相在国家体育馆举办的某汽车品牌发布会．并演唱了经典作品《下个路口见》与本年度最新单曲《酷》，大批涌至的歌迷将活动现场气氛一次次点燃。“春”字灯牌无数．歌迷尖叫连连．李宇春的好身材也被狂赞“完全可以秒杀所有车模。”

Primary resistance to crizotinib treatment in a non-small cell lung cancer patient with an EML4-ALK rearrangement:a case report

Crizotinib,a small molecular tyrosine kinase inhibitor,manifests dramatic responses in patients with non-small cell lung cancer with echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase(EML4-ALK)rearrangements.ALK gene point mutation is the primary mechanism of acquired crizotinib resistance;however,the intrinsic mechanism is not fully understood.Here,we report a patient with a low mutant allele fraction(MAF)of EML4-ALK rearrangement,who experienced primary resistance to crizotinib treatment.The patient was a 66-year-old Chinese man,who had a history of metastatic lung cancer and was treated with first-and third-generation epidermal growth factor receptor tyrosine kinase inhibitors(EGFR TKIs).After 14 months of osimertinib treatment,his disease progressed,and next-generation sequencing was performed from a liquid biopsy of the patient’s blood.An EML4-ALK rearrangement was found and crizotinib was administered.The patient’s lung lesions continued to progress after one month of crizotinib treatment,and pemetrexed-bevacizumab was initiated.After two cycles of chemotherapy,the metastatic cancers shrunk,and the patient maintained stable disease at his last follow-up.EML4-ALK rearrangements can happen in patients with EGFR-positive NSCLC,after acquired resistance to EGFR TKI treatment.The EGFR T790M and C797G mutations occur in cis is a critical mechanism of resistance to osimertinib therapy.The MAF of EML4-ALK rearrangements in cancer cells might be a predictive factor for crizotinib treatment.

Study on Action of Acupuncture on Ventromedial Nucleus of Hypothalamus in Obese Rats

Effects of acupuncture on the spontaneous discharge of nerve cells and levels of monoamine neurotransmitters in ventromedial nucleus of hypothalamus (VMH) of the obese rats were investigated. Results indicated that the levels of tyrosine (Tyr) and dopamine (DA) were lowered, the levels of 5-hydroxytryptamine (5-HT) and 5-hydoxyindole acetic acid (5-HIAA) increased, and the frequency of the spontaneous discharge of nerve cells in VMH lowered in the obese rat group as compared with the normal group. When acupuncture obtained the effect of weight reduction, the frequency of spontaneous discharges of nerve cells in VMH were markedly increased, and the levels of Tyr, DA and tryptamine (Typ) and 5-HT/5-HIAA ratio elevated, and the 5-HT level lowered. It is suggested that the virtuous regulative action of acupuncture on VMH might be one of the key factors in acupuncture for weight reduction.

Current research and treatment for gastrointestinal stromal tumors

Gastrointestinal stromal tumors(GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and have gained considerable research and treatment interest,especially in the last two decades. GISTs are driven by mutations commonly found in the KIT gene and less commonly in the platelet-derived growth factor receptor alpha gene,BRAF gene and succinate dehydrogenase gene. GISTs behave in a spectrum of malignant potential,and both the tumor size and mitotic index are the most commonly used prognostic criteria. Whilst surgical resection can offer the best cure,targeted therapy in the form of tyrosine kinase inhibitors(TKIs) has revolutionized the management options. As the first-line TKI,imatinib offers treatment for advanced and metastatic GISTs,adjuvant therapy in high-risk GISTs and as a neoadjuvant agent to downsize large tumors prior to resection. The emergence of drug resistance has altered some treatment options,including prolonging the first-line TKI from 1 to 3 years,increasing the dose of TKI or switching to second-line TKI. Other newer TKIs,such as sunitinib and regorafenib,may offer some treatment options for imatinib-resistant GISTs. New molecular targeted therapies are being evaluated,such as inhibitors of BRAF,heat shock protein 90,glutamine and mitogenactivated protein kinase signaling,as well as inhibitors of apoptosis proteins antagonist and even immunotherapy. This editorial review summarizes the recent research trials and potential treatment targets that may influence our future patient-specific management of GISTs. The current guidelines in GIST management from Europe,North America and Asia are highlighted.

Detection of tyrosine,trace metals and nutrients in cow dung:the environmental significance in soil and water environments

This study examined the dissolved organic matter(DOM) components of cow dung using a combination of fluorescence(excitation–emission matrix,EEM)spectroscopy and parallel factor(PARAFAC) modelling along with eleven trace metals using ICP-MS and nutrients(NH_4^+ and NO_3^-) using an AA3 auto analyser. EEM–PARAFAC analysis demonstrated that cow dung predominantly contained only one fluorescent DOM component with two fluorescence peaks(Ex/Em=275/311 nm and Ex/Em=220/311 nm),which could be denoted as tyrosine by comparison with its standard. Occurrence of tyrosine can be further confirmed by the FTIR spectra. Trace metals analysis revealed that Na,K and Mg were significantly higher than Ca,Fe,Mn,Zn Sr,Cu,Ni and Co. The NH_4^+ concentrations were substantially higher than NO_3^-.These results thus indicate that the dissolved components of the cow dung could be useful for better understanding its future uses in various important purposes.

EGFR tyrosine kinase inhibitor HS-10182 increases radiation sensitivity in non-small cell lung cancers with EGFR T790M mutation

Objective:To investigate the potential of HS-10182,a second-generation epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI),as a radiosensitizer in non-small cell lung cancer(NSCLC).Methods:Two cell lines of NSCLCs,A549 that possesses wild-type(WT)EGFRs and H1975 that possesses EGFR L858R/T790M double mutations,were treated with HS-10182 at various concentrations,and cell viabilities were determined using the MTS assay.The cells were tested by clonogenic survival assays to identify the radiosensitivity of both groups.Western blot was performed to analyze the expression of phosphorylated EGFR,AKT,DNA-dependent protein kinase,and catalytic subunit(DNA-PKcs)proteins.Immunofluorescence analyses were performed to examine the formation and changes in nuclearγ-H2AX foci.Cell apoptosis was examined by flow cytometry and Western blots for cleaved caspase-3,-8,-9,and cleaved poly ADP-ribose polymerase(PARP).Furthermore,we established xenograft models in mice and the effects of different treatments on tumor growth were then assessed.Results:Clonogenic survival assays revealed that HS-10182 significantly enhanced the radiosensitivity of H1975 cells but not A549cells[dose enhancement ratios(DERs)=2.36(P<0.05)vs.1.43(P>0.05)].Western blot results showed that HS-10182 increased the levels of cleaved caspase-3,-8,-9,and cleaved PARP in H1975 cells but not in A549 cells.In addition,flow cytometry analysis showed that HS-10182 enhanced irradiation-induced apoptosis in H1975.Immunofluorescence results found that HS-10182increased the average number ofγ-H2AX foci after irradiation in H1975 cells,but not in A549 cells.Combined radiation and HS-10182 treatment increased the expression of DNA-PKcs but this increase was more significant in H1975 cells than in A549 cells.Moreover,HS-10182 suppressed the increased expression of Rad50 in H1975 cells in response to irradiation.In vivo experiments found that the combined therapy significantly inhibited tumor growth.Conclusions:HS-10182 enhances the radiosensitivity of H1975 cells which is possibly because that HS-10182 could enhance irradiation-induced apoptosis,increase irradiation-induced DNA damage,and cause a delay in DNA damage repair.Our findings suggest that radiotherapy combined HS-10182 is a novel treatment for lung cancer cells which have acquired the T790M mutation.HS-10182 could be brought to the clinic as a radiosensitizer in NSCLCs with the EGFR T790M mutation.

Treatment and survival status of patients with EGFR mutation-positive stage Ⅳ lung adenocarcinoma: five-year follow-up results in the Ordos Area of Inner Mongolia, China

Objective We aimed to determine the epidermal growth factor receptor （EGFR） mutation status and treatment survival of patients with stage IV lung adenocarcinoma living in the Ordos area of Inner Mongolia, China. Methods EGFR testing and first-line tyrosine kinase inhibitor （TKI） treatment rates of patients with stage IV lung adenocarcinoma were analyzed from June 2012 to June 2016. Kaplan-Meier survival curves were constructed to compare patients who received different treatment strategies and those harboring different EGFR mutation statuses. Results EGFR testing and mutation rates were 65.60% and 52.90%, respectively, and improved continuously from June 2012 to June 2016. Among patients with EGFR mutations, 38.9% had EGFR 19 del, 48.2% had L858R, 4.2% had co-existing mutations in exons 19 and 21, and 8.4% had uncommon mutations. The median overall survival （OS） was 29.5, 26.5, and 16.0 months for patients receiving both TKI and chemotherapy, TKI alone, and chemotherapy alone, respectively （P = 0.047）. The OS was 26.5 and 30.0 months for patients harboring EGFR 19 del and L858R mutations, respectively （P = 0.096）. Conclusion The high OS rates of stage IV lung adenocarcinoma patients living in the Ordos area may be attributed to continuous improvements in EGFR testing and first-line TKI treatment rates. In the era of TKIs, chemotherapy for increasing OS times should be emphasized.

Biosynthesis of 4-hydroxyphenylpyruvic acid from L-tyrosine using recombinant Escherichia coli cells expressing membrane bound L-amino acid deaminase

4-Hydroxyphenylpyruvic acid （4-HPPA）, a kind of α-keto acid, is an intermediate in the metabolism of tyrosine and has a wide range of application in food, pharmaceutical and chemical industry. Using amino acids as raw material to prod uce the corresponding α-keto acid is thought to be both economic and efficient. Among the enzymes that convert amino acid to α-keto acid, membrane bound L-amino acid deaminase （mL-AAD）, which is anchored to the outer side of the cytomembrane, becomes an ideal enzyme to prepare α-keto acid since there is no cofactors needed and H2O2 production during the reaction. In this study, the mL-AAD from Proteus vulgaris was used to prepare whole-cell catalysts to produce 4-HPPA from L-tyrosine. The secretory efficiency of mL-AAD conducted by its own twin-arginine signal peptide （twin-arginine translocation pathway, Tat） and integrated pelB （the general secretory pathway, Sec）-Tat signal peptide was determined and compared firstly, using two pET systems （pET28a and pET20b）. It was found that the Tat pathway （pET28a-mlaad） resulted in higher cell-associated mL-AAD activity and cell biomass, and was more beneficial to prepare biocatalyst. In addition, expression hosts BI21 （DE3） and 0.05 mmol. L- 1 IPTG were found to be suitable for mL-AAD expression. The reaction conditions for mL-AAD were optimized and 72.72 mmol,L 1 4-HPPA was obtained from 100 mmol.L 1 tyrosine in 10 h under the optimized conditions. This bioprocess, which is more eco-friendly and economical than the traditional chemical synthesis ways, has great potential for industrial application.