Study of relationship between motion of mechanisms in gas operated weapon and its shock absorber

The article deals with the motion of the breech block carrier and the weapon casing of an automatic weapon mounted on a flexible carriage and the base of the weapon.Earlier works,which did not consider the dynamic properties of the base of the weapon,did not allow to reconcile the calculated and experimental results of the weapon casing displacement when shooting from firing rests.For the analysis of the motion of individual parts,the methods of mathematical modelling and firing experiments using a high-speed camera were chosen.Calculations show the best accord with experiment when modelling the system with 4 degrees of freedom.The oscillation of the system regarding the movement of the breech block carrier and the weapon casing was investigated under changed conditions of rate of fire,the use of a muzzle brake and different types of shock absorbers.The velocities and displacements of the weapon casing and the breech block carrier at different values of the impulse of the gases to the breech block carrier were determined.

A Th2-score in the tumor microenvironment as a predictive biomarker of response to Bacillus Calmette Guérin in patients with non-muscle invasive bladder carcinoma:A retrospective study

Intravesical Bacillus Calmette Guerin(BCG)is the gold standard therapy for intermediate/high-risk nonmuscle invasive bladder cancer(NMIBC).However,the response rate is~60%,and 50%of non-responders will progress to muscle-invasive disease.BCG induces massive local infiltration of inflammatory cells(Th1)and ultimately cytotoxic tumor elimination.We searched for predictive biomarker of BCG response by analyzing tumor-infiltrating lymphocyte(TIL)polarization in the tumor microenvironment(TME)in pre-treatment biopsies.Pre-treatment biopsies from patients with NMIBC who received adequate intravesical instillation of BCG(n=32)were evaluated retrospectively by immunohistochemistry.TME polarization was assessed by quantifying the T-Bet+(Th1)and GATA-3+(Th2)lymphocyte ratio(G/T),and the density and degranulation of EPX+eosinophils.In addition,PD-1/PD-L1 staining was quantified.The results correlated with BCG response.In most non-responders,Th1/Th2 markers were compared in pre-and post-BCG biopsies.ORR was 65.6%in the study population.BCG responders had a higher G/T ratio and a greater number of degranulated EPX+cells.Variables combined into a Th2-score showed a significant association with higher scores in responders(p=0.027).A Th2-score cut-off value>48.1 allowed discrimination of responders with 91%sensitivity but lower specificity.Relapse-free survival was significantly associated with the Th2-score(p=0.007).In post-BCG biopsies from recurring patients,TILs increased Th2-polarization,probably reflecting BCG failure to induce a pro-inflammatory status and,thus,a lack of response.PD-L1/PD-1 expression was not associated with the response to BCG.Our results support the hypothesis that a preexisting Th2-polarized TME predicts a better response to BCG,assuming a reversion to Th1 polarization and antitumor activity.

Influence of relative compaction and degree of saturation on the deformation characteristics of bentonite under freeze-thaw cycles

Bentonite,consisting of clay minerals of the montmorillonite group,has been widely used as an adsorbent and backfill material in nuclear waste disposal and groundwater remediation.It is challenging to use bentonite as a filling material in cold regions since bentonite is highly sensitive to thermal environmental changes,during which its bulk volume and microstructure change significantly.In this study,a series of one-dimensional and three-dimensional freeze-thaw tests were carried out within a closed system to investigate the influencing factors of the deformation of bentonite under freeze-thaw cycles.Results show that the initial soil water content greatly impacts bentonite's deformation during freeze-thaw cycles.For an initial higher degree of saturation(Sr),the expansion caused by the formation of ice lenses has a greater impact than the shrinkage induced by dehydration,ice-cementation,and so on.Conversely,bentonite tends to shrink at a lower degree of saturation during freezing.And the critical degree of saturation that determines bentonite's behavior of frost heave or frost shrinkage seems to be roughly 0.8.As the number of freeze-thaw cycles rises,initially uncompacted bentonite clay becomes more compacted,and initially compacted bentonite clay remains unchanged.

Morphology and morphometry of two hybridizing buntings at their hybrid zone in northern Iran reveal intermediate and transgressive morphotypes

The closely related Black-headed Bunting(Emberiza melanocephala,a western Palearctic lineage)and Red-headed Bunting(Emberiza bruniceps,an eastern Palearctic lineage)hybridize and replace each other south of the Caspian Sea.The parental species have distinct phenotypes and therefore morphology is useful for assessing hybridization in the contact zone.In the years of 1940 and 1977,quite a few hybrids were collected and studied morphologically.Since then,the hybrid zone appears to have expanded westwards,but there has been a time gap in the collection of morphological data.Here we reanalyze bunting specimens morphologically and compare the historical data with recent data.Morphometric and phenotypic traits from three time periods(1940,1977 and recent)were studied to assess phenotypic variation of hybrids,pattern of hybridization,and transgressive traits in the hybrid zone.Our results show that most of the birds in the hybrid zone exhibit intermediate phenotypes(both colors and morphometric characters),ranging from the pure phenotype of either of the parental species.However,hybridization has also produced novel phenotypes not seen in any of the parents.Using a canonical discriminant function analysis,the morphometric characters separated each parental species and the hybrids quite well.Our results showed morphometric intermediacy of hybrids in accordance with phenotypes.We observe a time trend in which recent hybrids are more similar to Red-headed Buntings phenotypically compared to historical samples.This pattern is likely a signature of a westward expansion of the Red-headed Bunting into the breeding range of the Black-headed Bunting.

电磁脉冲辐照所致海马神经细胞膜穿孔的原子力显微镜研究

目的:应用原子力显微镜(atomicforcemicroscopy熏AFM)对电磁脉冲辐照前后培养的海马神经元细胞膜进行观察,以探讨电磁脉冲对细胞损伤的机制。材料和方法:将新生的Wistar(24小时内)乳鼠解剖镜下分离出海马组织,将海马神经细胞稀释成1×106个/ml浓度的细胞悬液;将细胞悬液种植到六孔板中,2ml/孔。培养14天后,高场强EMP模拟源穴有界波模拟源雪,场强为6×104V/m,脉冲上升时间为20ns,脉宽为30μs熏频率包含0～100MHz。以2.5次/min熏辐照2分钟。并于辐照后即刻固定细胞,应用日本岛津穴SHIMADZU雪公司的SPM-9500J3型原子力显微镜对细胞表面进行接触式连续扫描。结果:电磁脉冲辐照后即刻就可引起大鼠海马神经元细胞膜表面大小不一、类圆形和不规则形的穿孔,穿孔最大口径和深度可达281.56nm×89.90nm×17.76nm。结论:电磁脉冲辐照后可直接导致海马神经元细胞膜的穿孔,提示细胞膜可能是电磁脉冲生物效应的靶部位之一。

代谢组学:一个迅速发展的新兴学科(英文)

对代谢组学的含义,中心任务,研究方法,样品要求,应用及其发展方向进行了简要综述. 系统生物学概念的诞生标志着研究哲学由“还原论”向“整体论”的变化. 系统生物学的中心任务就是要针对生物系统整体 (无论它是生物细胞,多细胞组织,器官还是生物整体),建立定量,普适,整体和可预测 (QUIP) 的认知. 具体而言,系统生物学研究就是要将给定生物系统的基因,转录,蛋白质和代谢水平所发生的事件,相关性及其对所涉及生物过程的意义进行整体性认识. 从而出现了许多的“组”和“组学”的新概念. 但是现已提出的一百多个“组”和“组学”,可以大体归纳为“基因组”/“基因组学”,“转录组”/“转录组学”,“蛋白质组”/“蛋白质组学”和“代谢组”/“代谢组学”四个方面. 显而易见,DNA,mRNA 以及蛋白质的存在为生物过程的发生提供了物质基础 (但这个过程有可能不发生!),而代谢物质所反映的是已经发生了的生物学事件. 因此代谢组学是对一个生物系统进行全面认识的不可缺少的一部分,是全局系统生物学 (global systems biology) 的重要基础,也是系统生物学的一个重要组成部分. 在现有的英文表述中,代谢组学同时存在两个不同的词汇和概念,即metabonomics 和 metabolomics. 尽管前者多用在动物系统而后者多用于植物和微生物系统,但这些概念的本质从他们的定义中能够得到较细致的了解. Metabonomics 的最初定义是就生物系统对生理和病理刺激以及基因改变的代谢应答的定量测定(“the quantitative measurement of the multi-parametric metabolic response of living systems to pathophysiological stimuli or geneticmodifications”). 我们认为这个定义现在可以更广泛地表述为:代谢组学是关于定量描述生物内源性代谢物质的整体及其对内因和外因变化应答规律的科学 (“Metabonomics is the branch of science concerned with the quantitative understandings of themetabolite complement of integrated living systems and its dynamic responses to the changes of both endogenous factors (such asphysiology and development) and exogenous factors (such as environmental factors and xenobiotics).”). 其中心任务包括 (1) 对内源性代谢物质的整体及其动态变化规律进行检测,量化和编录,(2) 确定此变化规律和生物过程的有机联系. Metabolomics 存在多个定义,但其精髓是:对一个生物系统的细胞在给定时间和给定条件下所有小分子代谢物质的定量分析(the quantitativemeasurement of all low molecular weight metabolites in an organism's cells at a specified time under specific environmentalconditions). 因此,metabolomics 可以译作“代谢物组学”. 不难看出,前者是对生物系统进行的整体和动态的认识 (不仅关心代谢物质的整体也关注其动态变化规律),而后者强调分析而且是个静态的认识概念. 因此可以认为,metabolomics 是metabonomics 的一个组成部分 (参看定义). 近年又有人提出了“dynamic metabolomics”的概念,这个概念所表达的含义十分接近“metabonomics”本身的含义. 所以,可以预见,随着这门新兴学科的发展和更深入讨论,这两个概念必将趋向一致. 因此我们建议,在中文表述中将“代谢组学”一词和英文中的 metabonomics 相对应,以避免不必要的混淆和争议. 就细胞系统而言,不仅存在细胞自身的代谢物质组成问题,存在细胞之间代谢物质交换的问题,也存在代谢过程所发生的位点问题. 因此,简单地分析代谢物质的总组成 (即代谢组) 缺乏“整体论”所要求的全面性,其意义有一定局限. 代谢组学属于全局系统生物学 (Global systems biology) 研究方法,便于对复杂体系的整体进行认识. 譬如,一个正常工作的人体包括“人体”本身和与之共同进化而来且共生的消化道微生物群体 (或称菌群),孤立地研究“人体”本身的基因,转录子以及蛋白质当然可以为人们认识人体生物学提供重要信息,但无法提供使人体正常工作不可缺少的菌群的信息. 人体血液和尿液的代谢组却携带着包括菌群在内的每一个细胞的信息,因此代谢组学方法对研究如人体这样复杂的进化杂合体十分有效. 正因如此,代谢组学已经广泛地应用到了包括药物研发,分子生理学,分子病理学,基因功能组学,营养学,环境科学等重要领域. 在代谢组学诞生的过去 6 年里,有关代谢组学的研究论文和专利以指数的形式逐年增长. 可以预见,这门新兴学科将应用到更为广泛的领域.

Activation and dramatically increased cytolytic activity of tumor specific T lymphocytes after radio-frequency ablation in patients with hepatocellular carcinoma and colorectal liver metastases

AIM： To assess if a specific cytotoxic T cell response can be induced in patients with malignant liver tumors treated with radio-frequency ablation （RFA）. METHODS： Six Patients with liver metastases of colorectal cancer and 6 with hepatocellular carcinoma （HCC） underwent RFA. Blood was sampled before, 4 and 8 wk after RFA. Test antigens were autologous liver and tumor lysate obtained from each patient by biopsy. Peripheral T cell activation was assessed by an interferon gamma （IFNγ） secretion assay and flow cytometry. T cells were double-stained for CD4/CD8 and IFNγ to detect cytotoxic T cells. The ratio of IFNγ positive and IFNγ negative T cells was determined as the stimulation index （SI）. To assess cytolytic activity, T cells were co-incubated with human CaCo colorectal cancer and HepG2 HCC cells and release of cytosolic adenylate kinase was measured by a luciferase assay. RESULTS： Before RFA SI was 0.021 （±0.006） for CD4^＋ and 0.022 （± 0.004） for CD8^＋T cells against nonmalignant liver tissue and 0.018 （± 0.005） for CD4^＋ and 0.021 （± 0.004） for CD8^＋ cells against autologous tumor tissue. Four weeks after RFA SI against tumor tissue increased to 0.109 （± 0.005） for CD4＋ and 0.11 （± 0.012） for CD8＋ T cells against HCC, and to 0.115 （± 0.031） for CD4^＋ and 0.15 （± 0.02） for CD8^＋ cells for colorectal metastases （P 〈 0.0001）. No increased SI was observed with nonmalignant tumor tissue at all time points. Before RFA cytolytic activity against the respect（ve cancer cells was low with 2.62 （± 0.37） relative luminescence units （RLU）, but rose more than 100 fold 4 and 8 wk after RFA. Spontaneous release was 〈 2% of maximum release in all experiments. CONCLUSION： Patients with primary and secondary tumors of the liver show a significant tumor-specific cytotoxic T-cell stimulation with a dramatically increased tumor specific cytolytic activity of CD8^＋ T cells after RFA.

基于NMR的代谢组学方法最新进展及应用(英文)

代谢组学的定义“对病理/生理刺激以及基因改变时生物体系动态的代谢响应进行多参数的定量测量”已被广泛接受.本文对代谢组学研究的最新进展及其在系统生物学中所发挥的作用进行了综述.在代谢组学方法研究方面,着重讨论了现代NMR技术的进展及其对代谢组学所产生的影响,同时也包括用于分离的HPLC及其与质谱的连用技术.对代谢组学广泛应用的概述,主要包括:对正常生理变化的新认识;药物和其他外源性化学物质的副作用;外源性物质对环境污染的影响以及逐渐增多的代谢组学方法在疾病检测中应用.

Sorafenib in breast cancer treatment:A systematic review and overview of clinical trials

AIM:To evaluate the current role of sorafenib,an oral multikinase inhibitor in the treatment of breast cancer.METHODS:An extensive search of the literature until March 2016 was carried out in Medline and clinicaltrials.gov,by using the search terms "sorafenib" and "breast cancer".Papers found were checked for further relevant publications.Overall,21 relevant studies were found,18 in advanced breast cancer(16 in stage Ⅳ and two in stages Ⅲ-Ⅳ) and three in early breast cancer.RESULTS:Among studies in advanced breast cancer,there were two trials with sorafenib as monotherapy,four trials of sorafenib in combination with taxanes,two in combination with capecitabine,one with gemcitabine and/or capecitabine,one with vinorelbine,one with bevacizumab,one with pemetrexed and one with ixabepilone,three trials of sorafenib in combination with endocrine therapy and two trials in women with brain metastases undergoing whole brain radiotherapy.In addition,there was one trial of sorafenib added to standard chemotherapy in the adjuvant setting,and two trials in the neoadjuvant setting.In general,sorafenib was well tolerated in breast cancer patients,though its dosage had to be adjusted in some trials,and discontinuation rates were high,particularly for the combination of sorafenib with anastrozole.Sorafenib monotherapy and combinations with taxanes,bevacizumab and ixabepilone showed inadequate efficacy,while efficacy results from combinations with gemcitabine and/or capecitabine and possibly tamoxifen were more promising.CONCLUSION:At present,sorafenib should not be used for the treatment of breast cancer outside of clinical trials and more clinical data are needed in order to support its standard use in breast cancer therapy.

The Sandfish's Skin:Morphology,Chemistry and Reconstruction

The sandfish is a lizard having the remarkable ability to move in desert sand in a swimming-like fashion. The most outstanding adaptations to this mode of life are the low friction behaviour and the extensive abrasion resistance of the sandfish skin against sand, outperforming even steel. We investigated the topography, the composition and the mechanical properties of sandfish scales. These consist of glycosylated keratins with high amount of sulphur but no hard inorganic material, such as silicates or lime. Remarkably, atomic force microscopy shows an almost complete absence of attractive forces between the scale surface and a silicon tip, suggesting that this is responsible for the unusual tribological properties. The unusual glycosylation of the keratins was found to be absolutely necessary for the described phenomenon. The scales were dissolved and reconstituted on a polymer surface resulting in properties similar to the original scale. Thus, we provide a pathway towards exploitation of the reconstituted scale material for future engineering applications.

Past,present and future of saline lakes:research for global sustainable development

The 12 th International Conference on Salt Lake Research was held in Langfang City,China from July 14 to 18,2014.Fifteen manuscripts of presentations have been retained for publication in this special issue.They are very diverse,covering the biology,physics,chemistry and geology of salt lakes,the history of hydrological research on the Dead Sea,the effects of socioeconomic and environmental policies by stakeholders on human populations,and the increasing salinization of freshwater lakes around the world.

Tendon injuries of the hand

Tendon injuries are the second most common injuries of the hand and therefore an important topic in trauma and orthopedic patients.Most injuries are open injuries to the flexor or extensor tendons,but less frequent injuries,e.g.,damage to the functional system tendon sheath and pulley or dull avulsions,also need to be considered.After clinical examination,ultrasound and magnetic resonance imaging have proved to be important diagnostic tools.Tendon injuries mostly require surgical repair,dull avulsions of the distal phalanges extensor tendon can receive conservative therapy.Injuries of the flexor tendon sheath or single pulley injuries are treated conservatively and multiple pulley injuries receive surgical repair.In the postoperative course offlexor tendon injuries,the principle of early passive movement is important to trigger an"intrinsic"tendon healing to guarantee a good outcome.Many substances were evaluated to see if they improved tendon healing;however,little evidence was found.Nevertheless,hyaluronic acid may improve intrinsic tendon healing.

桡骨远端骨折:不跨腕关节的外固定是一种治疗选择吗?前瞻性随机研究

桡骨远端骨折是成人常见的一种骨折.绝经期后的妇女最多见(男∶女=1∶8).受伤原因多为手掌撑地时的撞击伤.随骨质疏松程度、暴力大小和方向及手位置的不同而产生各种类型的骨折.其中桡骨远端关节外骨折即A2和A3型(AO分类法,相当于Colles骨折)约占50%.对A2和A3型骨折一般采用手法复位,有时悬挂牵引后再石膏绷带固定.不稳定性骨折加经皮克氏针固定.腕关节制动4～6周.长期制动和创伤导致的关节僵硬须做医疗体操强化治疗. 为了使腕关节至少能屈伸活动,Hofmann发明了一种活动性手外固定器,可使活动范围达到约30°.外固定器的活动轴须与腕关节的活动轴一致,以避免功能锻练时产生继发移位. 本研究的目的是在许多医院现有器械的基础上发展一种活动时能保持稳定不跨腕关节的系统 .我们采用AO的小型外固定器.

Microbial community structure and nitrogenase gene diversity of sediment from a deep-sea hydrothermal vent field on the Southwest Indian Ridge

A sediment sample was collected from a deep-sea hydrothermal vent field located at a depth of 2 951 m on the Southwest Indian Ridge. Phylogenetic analyses were performed on the prokaryotic community using polymerase chain reaction（PCR） amplification of the 16 S rRNA and nifH genes. Within the Archaea, the dominant clones were from marine benthic group E（MBGE） and marine group I（MGI） belonging to the phyla Euryarchaeota and Thaumarchaeota, respectively. More than half of the bacterial clones belonged to the Proteobacteria, and most fell within the Gammaproteobacteria. No epsilonproteobacterial sequence was observed. Additional phyla were detected including the Actinobacteria, Bacteroidetes, Planctomycetes, Acidobacteria, Nitrospirae, Chloroflexi, Chlorobi, Chlamydiae, Verrucomicrobia, and candidate divisions OD1, OP11, WS3 and TM6, confirming their existence in hydrothermal vent environments. The detection of nifH gene suggests that biological nitrogen fixation may occur in the hydrothermal vent field of the Southwest Indian Ridge. Phylogenetic analysis indicated that only Clusters I and III NifH were present. This is consistent with the phylogenetic analysis of the microbial 16 S rRNA genes, indicating that Bacteria play the main role in nitrogen fixation in this hydrothermal vent environment.

BCL2 inhibits cell adhesion, spreading, and motility by enhancing actin polymerization

BCL2 is best known as a multifnnctional anti-apoptotic protein. However, little is known about its role in cell- adhesive and motility events. Here, we show that BCL2 may play a role in the regulation of cell adhesion, spreading, and motility. When BCL2 was overexpressed in cultured murine and human cell lines, cell spreading, adhesion, and motility were impaired. Consistent with these results, the loss of Bcl2 resulted in higher motility observed in Bcl2- null mouse embryonic fibroblast （MEF） cells compared to wild type. The mechanism of BCL2 regulation of cell adhesion and motility may involve formation of a complex containing BCL2, actin, and gelsolin, which appears to functionally decrease the severing activity of gelsolin. We have observed that the lysate from MCF-7 and NIH3T3 cells that overexpressed BCL2 enhanced actin polymerization in cell-free in vitro assays. Confocal immunofluorescent localization of BCL2 and F-actin during spreading consistently showed that increased expression of BCL2 resulted in increased F-actin polymerization. Thus, the formation of BCL2 and gelsolin complexes （which possibly contain other proteins） appears to play a critical role in the regulation of cell adhesion and migration. Given the established correlation of cell motility with cancer metastasis, this result may explain why the expression Of BCL2 in some tumor cell types reduces the potential for metastasis and is associated with improved patient prognosis.

Cortisol levels and serum antioxidant status following chemotherapy

Chemotherapy results in increased free radical formation and depletion of tissue antioxidants. Moreover, patients receiving chemotherapy are under emotional stress, which is also accompanied by low antioxidant levels. In the present study, we measured cortisol, the main stress hormone, and total antioxidant capacity (TAC) in serum of 51 cancer patients during chemotherapy. Antioxidant activity was estimated by measuring the influence of serum in oxidation of ABTS (2,2'-azino-bis (3-ethylbenz-thiazoline-6-sulfonic acid to ABTS+ by methmyoglobin (Antioxidant kit of Cayman). Serum cortisol was measured using an ELISA colorimetric assay. Serum TAC was significantly decreased (75% decrease compared to normal levels, p = 0.001) in all patients during chemotherapy, while blood cortisol concentration was increased by 10%, (p = 0.044). Lower antioxidant levels and higher cortisol concentration were detected in patients receiving chemotherapeutic drugs daily, compared to the ones receiving chemotherapy once a week. A difference between sexes was observed with male patients presenting lower antioxidant status and higher cortisol levels than females. A significant and persistent decrease in antioxidant capacity accompanied by increased cortisol concentration was observed in all patients during chemotherapy. This fact, which is probably generated by biological and emotional stress, increases the probability of harmful side effects and organism weakening and needs to be considered during patients’ treatment.

First-line cisplatin,docetaxel,and cetuximab for patients with recurrent or metastatic head and neck cancer:A multicenter cohort study

BACKGROUND The targeted therapy cetuximab[directed at the epidermal growth factor receptor(EGFR)]in combination with 5-fluorouracil and platinum-based chemotherapy(the EXTREME regimen)has shown substantial efficacy for patients with recurrent or metastatic squamous cell carcinoma of the head and neck(R/M SCCHN).Thus,this scheme has been established as the preferred first-line option for these patients.However,more recently,a new strategy combining platinum,taxanes,and cetuximab(the TPEx regimen)has demonstrated similar efficacy with a more favorable toxicity profile in clinical trials.AIM To evaluate the safety and efficacy of the TPEx scheme as first-line therapy in advanced SCCHN in a multicenter cohort study.METHODS This retrospective multicenter cohort study included patients with histologically confirmed recurrent or metastatic SCCHN treated with first-line TPEx at five medical centers in Argentina between January 1,2017 and April 31,2020.Chemotherapy consisted of four cycles of docetaxel,cisplatin,and cetuximab followed by cetuximab maintenance therapy.Clinical outcomes and toxicity profiles were collected from medical charts.Treatment response was assessed by the investigator in accordance with Response Evaluation Criteria in Solid Tumors(version 1.1).Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events(version 4.0).RESULTS Twenty-four patients were included.The median age at diagnosis was 58 years(range:36-77 years).The majority of patients(83.3%)received at least four chemotherapy cycles in the initial phase.In the included group,the overall response rate was 62.5%,and 3 patients achieved a complete response(12.5%).The median time to response was 2.4 mo[95% confidence interval(CI):1.3-3.5].With a median follow-up of 12.7 mo(95%CI:8.8-16.6),the median progression-free survival(PFS)was 6.9 mo(95%CI:6.5-7.3),and the overall survival rate at 12 mo was 82.4%.Patients with documented tumor response showed a better PFS than those with disease stabilization or progression[8.5 mo(95%CI:5.5-11.5)and 4.5 mo(95%CI:2.5-6.6),respectively;P=0.042].Regarding the safety analysis,two-thirds of patients reported at least one treatment-related adverse event,and 25% presented grade 3 toxicities.Of note,no patient experienced grade 4 adverse events.CONCLUSION TPEx was an adequately tolerated regimen in our population,with low incidence of grade 3-4 adverse events.The median PFS were consistent with those in recent reports of clinical trials evaluating this treatment combination.This regimen may be considered an attractive therapeutic strategy due to its simplified administration,decreased total number of chemotherapy cycles,and treatment tolerability.

德国健康保险与预防性医疗服务

德国社会医疗保险具有悠久的历史，早在1883年俾斯麦执政时就引入了强制性医疗保险并奠定了社会保障的基础。德国的基本法规定了社会医疗保险的团结互助原则，保证了每个参保人拥有相同的医疗保障，这在法律上体现了公平合理的原则。从上世纪80年代至90年代，德国经济一直处于高速发展的繁荣期，社会医疗保险提供了完善而高标准的医疗保障。医疗保障无费用限制，除了支付疾病保障与医疗康复外还提供预防保健、健康促进等预防性服务。例如对于哮喘病人，医生可以处方给病人前往德国南部的温泉疗养一周，费用由社会医疗保险承担。随着两德统一，作为欧洲火车头的德国经济陷入了停滞状态，联邦政府加强了财政支出的控制。在健康保健领域，德国的健康支出占GDP的11％，高于英国和法国，在欧洲属较高水平，因此许多卫生领域专家质疑现有体制的缺陷：一方面，由于包括法律规管机构、健康基金以及医疗机构的多方参与，各方为了自己的利益，缺乏相互间的紧密合作，难以实现医疗保健架构的全面整合。另一方面，相对较高的健康保健投入并未带来相应的产出，特别是慢性疾病对医疗资源过度使用、滥用，或未充分使用等现象。因此如何保持德国在卫生保健领域的领先地位，实行卫生体制改革一直是执政党考虑的重要议题。

Dynamic changes in O-GlcNAcylation regulate osteoclast differentiation and bone loss via nucleoporin 153

Bone mass is maintained by the balance between osteoclast-induced bone resorption and osteoblast-triggered bone formation.In inflammatory arthritis such as rheumatoid arthritis(RA),however,increased osteoclast differentiation and activity skew this balance resulting in progressive bone loss.O-GlcNAcylation is a posttranslational modification with attachment of a single O-linkedβ-D-N-acetylglucosamine(O-GlcNAc)residue to serine or threonine residues of target proteins.Although O-GlcNAcylation is one of the most common protein modifications,its role in bone homeostasis has not been systematically investigated.We demonstrate that dynamic changes in O-GlcNAcylation are required for osteoclastogenesis.Increased O-GlcNAcylation promotes osteoclast differentiation during the early stages,whereas its downregulation is required for osteoclast maturation.At the molecular level,O-GlcNAcylation affects several pathways including oxidative phosphorylation and cell-cell fusion.TNFαfosters the dynamic regulation of O-GlcNAcylation to promote osteoclastogenesis in inflammatory arthritis.Targeted pharmaceutical or genetic inhibition of O-GlcNAc transferase(OGT)or O-GlcNAcase(OGA)arrests osteoclast differentiation during early stages of differentiation and during later maturation,respectively,and ameliorates bone loss in experimental arthritis.Knockdown of NUP153,an O-GlcNAcylation target,has similar effects as OGT inhibition and inhibits osteoclastogenesis.These findings highlight an important role of O-GlcNAcylation in osteoclastogenesis and may offer the potential to therapeutically interfere with pathologic bone resorption.

A Preliminary Annotated Checklist of the Amphibians and Reptiles of the Kulen Promtep Wildlife Sanctuary in Northern Cambodia

We present the first herpetological checklist for the Kulen Promtep Wildlife Sanctuary in northern Cambodia, with records of 22 species of amphibians and 33 species of reptiles belonging to 44 genera in 22 families. The checklist includes three species （Ingerophrynus macrotis, Micryletta inornata, Scincella melanosticta） which in Cambodia were formerly only known to occur in the Cardamom Mountains in the southwest of the country. Our findings highlight the importance of countrywide herpetological baseline surveys in lowland habitats.