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CRISPR/Cas9 technologies have revolutionized our understanding of gene function in complex biological settings, including T cell immunology. Current CRISPR-mediated gene editing strategies in T cells require in vitro stimulation or culture that can both preclude the study of unmanipulated naive T cells and alter subsequent differentiation. In this study, we demonstrate highly efficient gene editing within uncultured primary naive murine CD8+ T cells by electroporation of recombinant Cas9/sgRNA ribonucleoprotein immediately prior to in vivo adoptive transfer. Using this approach, we generated single and double gene knockout cells within multiple mouse infection models. Strikingly, gene deletion occurred even when the transferred cells were left in a naive state, suggesting that gene deletion occurs independent of T cell activation. Finally, we demonstrate that targeted mutations can be introduced into naive CD8+ T cells using CRISPR-based homology-directed repair. This protocol thus expands CRISPR-based gene editing approaches beyond models of robust T cell activation to encompass both naive T cell homeostasis and models of weak activation, such as tolerance and tumor models.

Lung cancer carries the highest morbidity and mortality out of all malignancies in the world. About 85% of all cases are non-small cell lung cancer (NSCLC). Surgery is currently the optimal treatment for early-stage NSCLC, however, the postoperative recurrence rate is relatively high and the long-term survival of these patients is still a problem to be overcomed. Previous studies have shown that early-stage NSCLC patients may benefit from preoperative neoadjuvant chemotherapy when compared to surgery alone, although the benefit is only moderate. More recent publications indicate that immune checkpoint blockade may have better potential in neoadjuvant therapy, with reported major pathological response rates at 20% to 85%, compared to chemotherapy alone. Phase Ⅲ random clinical trials are being implemented to confirm the effect of neoadjuvant immunotherapy in NSCLC. Meanwhile, a number of questions remain unanswered, including the time and course of neoadjuvant immunotherapy, the evaluation criteria of immune-related efficacy, the standardization of pathological evaluation, and how to avoid delays in surgery or misjudgment caused by pseudo-progression.早期非小细胞肺癌的治疗以手术为主，但术后复发率较高，患者如何获得长期生存仍然是亟待攻克的难题。既往研究结果显示，术前新辅助化疗较单纯手术可使患者有更好的生存获益，但获益程度尚不令人满意。近期研究结果显示，将免疫治疗用于新辅助治疗极具潜力，可使20%~85%的病例获得主要病理学缓解，优于既往新辅助化疗研究的数据。更多的三期随机对照研究正在进行，试图证实这一疗法在非小细胞肺癌治疗中的作用。与此同时，目前仍有诸多问题尚待回答，如新辅助免疫治疗的时间与疗程、免疫相关疗效评估标准、病理学评估的标准化、规避因假性进展导致的治疗延迟或决策错误的方法等。.

Background Although his bundle pacing (HBP) can achieve physiological electrical activation of the ventricles, its clinical use is limited by lower success rates, high and unstable pacing thresholds and loss of capture. Left bundle branch pacing (LBBP) has been proved to be able to correct Left bundle branch block (LBBB) and generate a narrower QRS duration than conventional RV pacing. However, its effects on ventricular synchronism and contraction function remains unknown. The current study is aimed to compare the echocardiographic characteristics between HBP and LBBP, and to explore whether LBBP leads to a comparable cardiac synchrony and deformation in comparison with HBP. Methods Forty-six pacing-indicated patients were prospectively enrolled. Twenty-nine patients underwent LBBP (17 male patients, mean age 69.6±13.7yrs, the LBBP group) and 17 patients underwent HBP (13 male patients, mean age 70.4±14.7yrs, the HBP group). LBBP was achieved by trans-septal method in the basal ventricular septum. Left ventricular end diastolic volume (LVEDV), left ventricular end systolic volume (LVESV), left ventricular ejection fraction (LVEF), and tricuspid annulus plane systolic excursion (TAPSE) were obtained. Strains and time to peak strains of right ventricular free wall and 16 left ventricle segments were analyzed using two-dimensional speckle tracking echocardiography (2D STE). The standard deviation of time to peak strains of 16 left ventricular segments was calculated as PSD. Results Compared to the baseline, time to peak longitudinal strain (TTPS) of apical septum, apical lateral wall were shortened after 6 months of HBP, while they didn't change significantly after 6 months of LBBP. After pacemaker implantation, the LBBP group had a delayed TTPS of apical septum, apical lateral wall and basal RV free wall than the HBP group (LBBP vs. HBP: apical septum,358.44±61.98ms vs. 296.43±29.47ms; apical lateral wall, 373.11±55.80ms vs. 299.00±83.45ms; basal RV free wall, 404.31±72.93ms vs. 334.50±39.95ms, all p0.05). Compared to the baseline, global left ventricular longitudinal strain (LVGLS) and longitudinal strain of RV free wall (RVLS) were deteriorated after 6 months of HBP, while they were preserved in the LBBP group. After 6-month pacing, LVGLS and RVLS were significantly stronger in the LBBP group than those in the HBP group. (LVGLS, −16.10±3.75% vs. −13.18±4.11%; RVLS, −17.50±5.46% vs. −13.70±4.35%, both p Conclusion Patients received LBBP had a comparable left ventricular synchronism and a better myocardial contraction compared to patients with HBP. LBBP may be a promising alternative pacing strategy. Two-dimensional STE is more sensitive than conventional echocardiography in assessing cardiac synchrony and segmental deformation.

目的 探讨我国GATA2突变相关儿童原发性骨髓增生异常综合征（MDS）的发生情况、临床特点及分子生物学特征。 方法 回顾性分析2007年1月至2018年1月129例儿童原发性MDS患者临床资料，采用二代测序技术检测GATA2及髓系恶性肿瘤相关基因突变情况。分析基因突变谱及其与临床表现型的关系。 结果 在所有129例患者中，11例（8.5%）检出GATA2胚系突变。在50例MDS伴原始细胞增高（MDS-EB）和急性髓系白血病伴MDS相关改变（AML-MRC）患者中，GATA2胚系突变占14.0%。GATA2突变多位于第二个锌指（ZF2）区。多因素分析结果显示，SETBP1体细胞突变（P=0.041，OR=9.003，95%CI 1.098~73.787）和独立的7号染色体单体（P=0.002，OR=24.835，95%CI 3.305~186.620）与GATA2胚系突变显著相关。与GATA2野生型的患者相比，GATA2突变型患者中位发病年龄更大[8（1~16）岁对6岁（1月龄~18岁），P=0.035]，更易伴有7号染色体单体（72.7%对5.2%，P

Lung cancer, which is typically diagnosed at later stages, is a leading cause of cancer death among both males and females given its highly invasive and rapidly metastasizing nature. Rho GTPase activating protein 15 (ARHGAP15) is a member of the RhoGAP family and functions in multiple biological processes, such as cell proliferation and migration. However, the effect of ARHGAP15 in lung cancer and its underlying molecular mechanisms remain unclear.In this study, immunohistochemistry and Real Time PCR were performed to detect ARHGAP15 expression in lung cancer tissues and cells. Proliferation, transwell, and Western blot assays were further performed to explore the role and underlying mechanism of ARHGAP15 in lung cancer.Reduced ARHGAP15 expression was observed in lung cancer tissues and cells. In vitro upregulation of ARHGAP15 in lung cancer cells strongly suppressed cell proliferation, migration, and invasion and was accompanied by reduced matrix metalloproteinase-2 (MMP2), MMP9, vascular endothelial growth factor (VEGF) expression, and the phosphorylation of the signal transducer and activator of transcription-3 (p-STAT3). In contrast, interleukin-6 (IL-6) had the opposite effect and the induction of IL-6 was counteracted by ARHGAP15 upregulation. In addition, the proliferation, migration, and cell invasion induced by ARHGAP15 silencing were potentially inhibited by the STAT3 inhibitor AG490 (100 µM), MMP2, MMP9, VEGF, and p-STAT3 levels decreased.These results suggest that ARGFAP15 suppressed the proliferation and metastasis of lung cancer cells, which may occur through the inhibition of MMP2, MMP9, and VEGF expression via the STAT3 pathway inactivation.

患儿 男，16月龄，5月龄起出现反复腹泻及便血，伴有间断发热及低蛋白血症，曾调整氨基酸配方粉喂养及给予抗菌药物治疗但效果均欠佳。肠镜检查示直肠至降结肠所见各处黏膜充血明显、活动性出血，广泛黏膜糜烂及浅溃疡。肠黏膜病理：结肠黏膜上皮下及固有膜内见片状增生的组织细胞，组织细胞S-100阳性，CD1a阳性，个别细胞Langerin阳性。确诊为"朗格罕组织细胞增生症（胃肠道受累）"。随访至3岁，患儿相继出现颅骨及神经系统受累。朗格罕组织细胞增生症肠道受累罕见，但仍需在儿童慢性腹泻、便血、蛋白丢失性肠病、炎症性肠病等消化道疾病的诊断过程中作为鉴别诊断并引起重视。.

Previous studies have indicated that β2-adrenergic receptor (ADRB2) genetic polymorphism is related to the risk of asthma, but the results still have some controversy and uncertainty. To this end, the meta-analysis was performed, including all studies that can be used to assess the correlation between ADRB2 polymorphism and asthma susceptibility.The related papers on ADRB2 polymorphisms and asthma were systematically reviewed in databases of PubMed, EMBASE, Cochrane Library, and WanFang, Odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were measured. The sensitivity analysis and publication bias were evaluated to investigate the correlation.This meta-analysis included 57 papers in total involving 11,157 cases and 12,281 controls. Results illustrated that the C79G variant genotypes owned a reduced effect on asthma susceptibility (G vs. C: OR=0.94, p=0.037). In the age stratification analysis, C79G polymorphism owned a reduced effect on asthma risk for children (GG vs. CC: OR=0.69, p=0.002; GG vs. CC+CG: OR=0.65, p0.001). Furthermore, in the ethnic stratification analysis, the C79G variant genotypes also owned a reduced effect on asthma in Asians (GG vs. CC: OR=0.80, p=0.027; GG vs. CC+CG: OR=0.81, p=0.02). Besides, for A46G polymorphism, the ethnic stratification analysis demonstrated that the A46G variant owned an increased effect on asthma susceptibility among Caucasians (G vs. A: OR=1.15, p=0.043). For C491T polymorphism, a considerable reduced effect was found between C491T and asthma susceptibility for children (CT vs. CC: OR=0.70, p=0.03). In the ethnic stratification analysis, the effect was also considerable in the Caucasian subjects.The present meta-analysis demonstrated that C79G and C491T polymorphism may be a defensive factor for asthma, while A46G polymorphism may be a risk factor for asthma among the Caucasian population.

Two stages, induction stage and pore-formed stage, were distinguished in Al2Au’s dealloying process in HCl solutions by OCP, SEM and XPS characterization. In induction stage, the Au state with binding energy 85.4 eV (labelled as Al2Au (I)) was transformed into the state 84.7 eV (Al2Au (II)); in pore-formed stage, nanoporous structure started to be formed, Al2Au (II) and residual Al2Au (I) were transformed into the state 83.7 eV (pure Au). Multi-resolution analysis on OCP noise revealed that the induction stage and pore-formed stage undergo different corrosion modes: the former is local corrosion and the latter is global corrosion.

The molecular clock is a valuable and widely used tool for estimating evolutionary rates and timescales in biological research. There has been considerable progress in the theory and practice of molecular clocks over the past five decades. Although the idea of a molecular clock was originally put forward in the context of protein evolution and advanced using various biochemical techniques, it is now primarily applied to analyses of DNA sequences. An interesting but very underappreciated aspect of molecular clocks is that they can be based on genetic data other than DNA or protein sequences. For example, evolutionary timescales can be estimated using microsatellites, protein folds, and even the extent of recombination. These genome features hold great potential for molecular dating, particularly in cases where nucleotide sequences might be uninformative or unreliable. Here we present an outline of the different genetic data types that have been used for molecular dating, and we describe the features that good molecular clocks should possess. We hope that our article inspires further work on the genome as an evolutionary timepiece.

In the past few years, extreme weather events have threatened operations of power systems. The improvement of resilience for power system becomes crucial. This paper proposes an optimal restoration strategy, considering the resilience index of power transmission systems in restoration processes. Firstly, a typhoon is taken as an example to establish an extreme weather event impact model to obtain the failure probability of lines. Then Monte Carlo method is used to generate fault sets. For each restoration time point, the optimal restoration model is used to acquire the maximum recovery loads. The resilience index of system can be obtained by the resilience assessment methodology during restoration. Finally, the proposed strategy is compared with distance-based strategy in IEEE 6-bus system, which demonstrates the superiority of the proposed strategy.

The reports of liver dysfunction during pregnancy or postpartum have gradually increased in pregnant women who are chronic carriers of hepatitis B virus (HBV), but there is no consensus on when to intervene and how to deal with it. This article reviewed recent literature reports and found that pregnant women who are chronic carriers of HBV, regardless of intervention of nucleos(t)ide analogs (NAs), have a certain proportion of hepatitis flares or severe disease during pregnancy and postpartum, suggesting that postpartum drug withdrawal is not always safe, and close follow-up is required. Furthermore, it recommends that treatment should be in accordance to the gestational weeks and ALT levels. NAs are the main treatment choice in the onset of hepatitis flares during pregnancy, however, postpartum hepatitis flares requires NAs or interferon therapy, and it have been reported that combination of NAs and interferon might achieve higher therapeutic response.随着临床上对慢性乙型肝炎病毒携带孕妇母婴阻断的重视，该类人群在妊娠期或产后出现肝功能异常的报道逐渐增多，但何时干预、处理方法等问题尚未形成共识。现回顾近期文献报道，发现慢性乙型肝炎病毒携带孕妇，无论是否采用核苷(酸)类似物(NAs)干预，于妊娠期及产后均有一定比例的肝炎发作、甚至重症化，提示产后并非均能安全停药，需要密切随访。建议根据妊娠周数及丙氨酸氨基转移酶水平分类处理。在妊娠期肝炎发作，采用NAs为主的治疗，产后肝炎发作者可采用NAs或干扰素治疗。有报道采用NAs和干扰素联合治疗可达到更高的治疗目标。.

More than 20 viruses are known to infect strawberry (Fragaria ananassa), and a substantial number of these include new viruses identified since 2000 that can contribute to disease complexes (2). The most serious virus related losses in commercial strawberries are caused by aphid transmitted viruses (3,4,5). A survey was undertaken from 2012 to 2013 to investigate virus prevalence in commercial strawberries in rural areas of Hebei Province around Beijing, China, that were exhibiting virus symptoms. Visual observations revealed that the incidence of virus-like symptoms ranged from 30 to 50% of the plants and these symptoms included yellowing, leaf malformation, sometimes combined with severe stunting and deformed flowers or fruits. Leaf samples were tested for Strawberry vein banding virus (SVBV), Strawberry mottle virus (SMoV), Strawberry mild yellow edge virus (SMYEV), and Strawberry crinkle virus (SCV), which are the four most prevalent aphid-transmitted viruses in single or mixed infections (2). Testing was conducted by RT-PCR using total RNA extracted from fresh symptomatic strawberry leaves (3). SVBV was detected in 58 of 190 samples, but all of the samples tested negative for SMoV, SMYEV, and SCV. Aphids were present on many of the plants, so the samples were tested for Cucumber mosaic virus (CMV) because CMV is prevalent in Beijing gardens and farms, and recently had been shown to infect maize in China (5). This RT-PCR was carried out with the CMV primer pair CM420-F (5′-TGATTCTACCGTGTGGGTGA-3′) and CM420-R (5′-CCGTAAGCTGGATGGACAAC-3′) to amplify a portion of the capsid protein coding region and the conserved 3′non-translated regions of the genomic RNAs. This test revealed the presence of 43 CMV-positives out of 190 samples, and only 16 of these samples were co-infected with both SVBV and CMV. Samples infected with CMV only had leaf malformations and yellowing, while no CMV was found in symptomless samples. One of the amplified, CMV-specific DNA fragments was sequenced directly from the PCR product and showed 93.8% nucleotide sequence identity and 100% amino acid sequence identity to the CMV subgroup I (GenBank Accession No. D10538) (1). Subsequent ELISA tests for the CMV presence verified the RT-PCR results (Agdia, Elkhart, IN), and transmission electron microscopy observations revealed 28 nm spherical particles characteristic of CMV in strawberry samples tested positive for CMV. However, we were unable to detect either CMV or SVBV in 89 of the 169 samples from symptomatic plants, which suggested possible presence of the other pathogen(s). To the best of our knowledge, this is the first report of natural infections of CMV in strawberry plants. These data suggests that CMV is a potential threat to strawberry production. References: (1) M. Q. K. Andrew et al. Virus taxonomy: IXth Report of the ICTV, 970, Elsevier, 2012. (2) R. R. Martin and I. E. Tzanetakis. Plant Dis. 97:1358, 2013. (3) J. R. Thompson et al. J. Virol. Methods 111:85, 2003. (4) I. E. Tzanetakis et al. Plant Dis. 90:1343, 2006. (5) R. Wang et al. J. Phytopathol. 161: 880, 2013.

软组织透明细胞肉瘤（CCS）是一种具有黑色素细胞分化的软组织恶性肿瘤，具有相对特征性病理学特征，具有t（12，22）（q13；q12）易位，产生EWS（22q12）/ATFl（12q13）融合基因，主要发生于软组织，发生于舌十分罕见，我们收集1例2017年4月就诊于福建省立医院病理科的舌部软组织CCS患者资料，分析其临床病理学特征，为治疗及预后提供依据。.

Mitogen- and stress-activated kinase (MSK) 1 is a nuclear serine/threonine kinase. In the central nervous system, it plays an important role in regulating cell proliferation and neuronal survival; it is also involved in astrocyte inflammation and the inhibition of inflammatory cytokine production. However, its specific role in spinal cord injury is not clear. Here, we aimed to elucidate this role using an in vivo animal model. In this study, we found that MSK1 is gradually decreased, starting 1 day after spinal cord injury and to its lowest level 3 days post-injury, after which it gradually increased. To further investigate the possible function of MSK1 in spinal cord injury, we interfered with its expression by utilizing a small interfering RNA (siRNA)-encoding lentivirus, which was injected into the injured spinal cord to inhibit local expression. After MSK1 inhibition, we found that the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β were increased. Moreover, the expression of IL-10 was decreased. In addition, neuronal apoptotic cells were increased significantly and expression of the apoptosis-related protein caspase-3 was also increased. Ultrastructural analysis of nerve cells also revealed typical neuronal apoptosis and severe neuronal damage. Finally, we found that hindlimb motor function decreased significantly with MSK1 knockdown. Therefore, our findings suggest that the inhibition of this protein promotes inflammatory responses and apoptosis and suppresses functional recovery after spinal cord injury. MSK1 might thus play an important role in repair after spinal cord injury by regulating inflammation and apoptosis. Electronic supplementary material The online version of this article (10.1007/s12031-019-01298-9) contains supplementary material, which is available to authorized users.

To investigate the changes of bone mineral density (BMD) and serum bone turnover factor in newly diagnosed systemic lupus erythematous (SLE) patients.Eighty newly diagnosed SLE patients and 80 age and gender matched healthy controls were enrolled. None of the SLE patients had ever received glucocorticoid, immunosuppressive agents or vitamin D. BMD was measured at radius,lumbar spine and hip by dual X ray absorptiometry (DXA). Bone turnover markers including serum levels of tartrate-resistant acid phosphatase 5b (TRAP5b),bone alkaline phosphatase (BAP) and 25-hydroxy vitamin D3 (25-OH-VD3) were measured by enzyme-linked immunosorbent assay (ELISA). Logistic regression was employed to analyze the risk factors associated with decreased BMD.Mean age of the SLE patients was (32.8±12.4) years, and 85% were female, none of whom were post-menopausal. BMD was significantly reduced in all the measured sites, compared with the healthy controls. Sixteen (20%) of the patients were osteopenic in at least one site measured locations. The serum levels of 25-OH-VD3 were markedly reduced in the newly diagnosed SLE patients than those of the normal controls [(46.1+12.3) nmol/L vs. (25.4+11.2) nmol/L, P0.001)]. The serum levels of 25-OH-VD3 in the SLE patients with nephritis were much lower than those without nephritis (P=0.04). A significant negative correlation was demonstrated between the serum concentration of 25-OH-VD3 and the disease activity scores as measured by SLE disease activity index (SLEDAI) (r=-0.3,P=0.001). The serum TRAP5b concentration was positively correlated with SLEDAI (r=0.435,P=0.003). Age (P=0.058) and SLEDAI (P=0.085) were probably associated with decreased BMD in Logistic regression analysis.The study showed reduced BMD in untreated SLE patients. The role of chronic inflammation was of probable importance in bone metabolism.

The dielectric properties of Ba0.96Sr0.04Zr0.04LnxTi0.96–xO3–δ (Ln = Y, Dy, Gd, Yb) ceramics were investigated in this work. The permittivity dependence on temperature showed the Curie temperature of the investigated ceramic samples was around 100 °C. The permittivity (>10000) at room temperature is obtained when the x is 0.004 and 0.003 for Y3+ and Dy3+, respectively. The origin of the dielectric abnormality may result from the amphoteric properties of Y3+ and Dy3+.

This study aims to compare the release profile of antibiotics when loaded onto a new mineralized collagen (MC) putty with conventional polymethyl methacrylate (PMMA) cement as well as their feasibility for clinical application for orthopaedic wounds. Two types of antibiotic-loaded implants were fabricated by physically mixing Imipenem or Vancomycin with either PMMA or MC in a quantifiable manner. Subsequently, the release profiles of antibiotics and their inhibitory effects on bacterial growth were evaluated both in vitro and in vivo. In comparison to PMMA, the antibiotic-loaded MC putty was easier to make with high flexibility of antibiotic selection based on drug sensitivity test, and surgeon friendly moldability. The inhibitory effects of bacterial growth lasted 24 h post-intramuscular implantation. The Imipenem-loaded MC putty was confirmed to be superior as a local drug delivery system (LDDS) over PMMA cement, the only type of antibiotics carrier orthopaedic clinics currently use.

N-doped graphene oxide (NGO) thin film was synthesised by photochemical reduction method in an ammonia atmosphere. The NGO film obtained has high N content of 9·77 at.%. The photocurrent amplitude for the NGO film is ca. 8·29 μA at 5 mV. The NGO film exhibits significant photocurrent enhancement with a high-enhancement ratio of ∼1200% at 0·5 mV and enhancement ratio for NGO film is nearly twice of that for the reduced graphene oxide (RGO) film at all different bias voltage, which may attribute to the high content of N.

Single arm trial (SAT) was widely used for new drug application (NDA) of novel anti-cancer drugs in recent years. The listing time was greatly shortened by SAT while comparing with randomized controlled trials (RCT). Thus, the companies intended to get NDA through SAT. To encourage innovation and accelerate the developments of anti-cancer agents, we summarize the background and key issues of SAT, discuss the conditions of accepting SAT for NDA, and systematically elaborate the design and principles of SAT in this review.近年来单臂试验被越来越多地用于抗肿瘤新药的注册申请。与随机对照试验比较，单臂试验显著缩短了药品的上市时间，因此企业均期望以单臂数据支持新药注册。为鼓励创新，加速抗肿瘤药物研发，文章从单臂试验的产生背景、核心问题以及单臂试验支持注册的标准等方面，系统阐述了抗肿瘤药物单臂试验的设计和原则。.

Slope stability analysis based on the finite element method (FEM) is a powerful tool comparing with the traditional limit equilibrium methods. However, severe mesh distortion of the traditional Lagrangian FEM may result in convergence difficulty and the obtained factor of safety (FOS) is not reliable. In this study, a stability analysis based on the Coupled Eulerian-Lagrangian (CEL) method is presented. The method allows materials to flow between different grids regardless of mesh distortion. In an example problem, both shear strength reduction (SSR) technique and gravity increasing (GI) technique are utilized to study the capability of the proposed method. The result shows that the method can effectively simulate the entire process of failure to post failure state. The estimated factor of safety (FOS) rarely varies with the mesh density and agrees well with the previous studies based on the traditional Lagrangian FEM method. The FOS by the GI technique is slightly smaller than that by the SSR technique.

The ultimate bearing capacity of the driven piles is mainly composed of the ultimate shaft resistance and the ultimate base resistance. The frequent appearance of the set-up effects of the driven piles will be conductive to the improvement of the ultimate shaft resistance after pile driving. The fundamental purpose of this paper is to study the influence of the set-up effects on the design resistance factor and the factor of safety (FS) of the driven piles based on the load and resistance factor design (LRFD) criteria. The set-up effects factor \( \left( \alpha \right) \) and the ratio \( \left( \varepsilon \right) \) of the initial ultimate shaft resistance to the initial ultimate bearing capacity are used to calibrate the formulas for estimating the resistance factor and FS of the driven piles. Meanwhile, the influence of the factor α and the ratio e on the design resistance factor and FS of the driven piles are studied. Analysis indicates that the smaller design resistance factor will be determined for the driven piles with the stronger set-up effects, and so it is for the larger e. And the smaller FS will be estimated for the driven piles with the stronger set-up effects, and so it is for the larger e. However, analysis also demonstrates that the design resistance factor and the estimation FS are nearly not influenced by the factor α and the ratio e when they are larger than the certain values.

The US2 protein has been reported to contribute to duck enteritis virus (DEV) infection; however, its kinetics and localization during infection, and whether it is a component of virion, have not been previously reported. To elucidate the function of DEV US2, US2 was amplified by polymerase chain reaction (PCR) and inserted into pET-32a(+); this was expressed, the recombinant US2 protein was purified, and a polyclonal antibody generated. In addition, the kinetics and localization of the US2 gene and protein were determined by quantitative real-time fluorescent PCR, ganciclovir (GCV), and cycloheximide (CHX) treatment, western-blot, and indirect immunofluorescence assay. The packaging of US2 into DEV virions was revealed by a protease protection assay. US2 was found to be transcribed 24 h post-infection (pi) and peaked at 72 h pi; the US2 protein was detected 48 h pi, except in the presence of GCV or CHX. US2 was packed into virions and also localized to the plasma membrane and cytoplasm in infected cells. The results showed that the DEV US2 is a late gene, and that its encoding protein could be a tegument component localized mainly in the cytoplasm. This study provides useful data for the further analysis of DEV US2, including an explanation for the genetic conservation among alphaherpesviruses.

目的 探讨替代活化型巨噬细胞（M2 MΦ）和多发性骨髓瘤（MM）早期治疗反应的关系及其在发病机制中的可能作用。 方法 采用免疫组化法标记240例MM患者骨髓标本中的MΦ；建立体外M2 MΦ诱导培养体系，构建Transwell共培养模型与RPMI 8226和U266细胞共培养，CCK-8法检测M2 MΦ对细胞增殖的影响，流式细胞术检测对地塞米松（1 µ mol/L）诱导骨髓瘤细胞凋亡的影响，ELISA法检测对TNF-α和IL-6表达的影响，real time PCR法检测对趋化因子、血管内皮生长因子（VEGF）及其受体表达的影响。 结果 ①依据骨髓组织M2 MΦ浸润程度将患者分为高浸润组（92例）和低浸润组（148例），高浸润组患者早期治疗有效率明显低于低浸润组，差异有统计学意义（23.9%对73.0%，χ2=60.31，P

To ensure product quality, the inspection and analysis were carried out on the ultra high-strength steel welded shell with transverse rupture after qualified hydraulic blasting test. Firstly, we carried out spot investigation of hydraulic blasting test, breakage morphological analysis, investigation on production technology, reexamination of wall-thickness and X-ray film of welding joint; in case of different opinions on fast analysis, then, we carried out contrast detection and analysis on stripe of fracture, metallographic analysis on cross section of welding joint, TEM detection and analysis on fracture, and inspection and analysis on welding size and offset. The analysis results showed that, the transverse rupture of test sample after hydraulic blasting test was caused by the failure of part incomplete joint penetration on welding joint, which was due to welding arc deviation. Therefore, with the improvements of welding equipments, tooling and operation methods to prevent radial and weld offset, the welding quality was assured and improved.