Calculus bovis inhibits M2 tumor-associated macrophage polarization via Wnt/β-catenin pathway modulation to suppress liver cancer

BACKGROUND Calculus bovis(CB),used in traditional Chinese medicine,exhibits anti-tumor effects in various cancer models.It also constitutes an integral component of a compound formulation known as Pien Tze Huang,which is indicated for the treatment of liver cancer.However,its impact on the liver cancer tumor microenvironment,particularly on tumor-associated macrophages(TAMs),is not well understood.AIM To elucidate the anti-liver cancer effect of CB by inhibiting M2-TAM polarization via Wnt/β-catenin pathway modulation.METHODS This study identified the active components of CB using UPLC-Q-TOF-MS,evaluated its anti-neoplastic effects in a nude mouse model,and elucidated the underlying mechanisms via network pharmacology,transcriptomics,and molecular docking.In vitro assays were used to investigate the effects of CB-containing serum on HepG2 cells and M2-TAMs,and Wnt pathway modulation was validated by real-time reverse transcriptase-polymerase chain reaction and Western blot analysis.RESULTS This study identified 22 active components in CB,11 of which were detected in the bloodstream.Preclinical investigations have demonstrated the ability of CB to effectively inhibit liver tumor growth.An integrated approach employing network pharmacology,transcriptomics,and molecular docking implicated the Wnt signaling pathway as a target of the antineoplastic activity of CB by suppressing M2-TAM polarization.In vitro and in vivo experiments further confirmed that CB significantly hinders M2-TAM polarization and suppresses Wnt/β-catenin pathway activation.The inhibitory effect of CB on M2-TAMs was reversed when treated with the Wnt agonist SKL2001,confirming its pathway specificity.CONCLUSION This study demonstrated that CB mediates inhibition of M2-TAM polarization through the Wnt/β-catenin pathway,contributing to the suppression of liver cancer growth.

城市轨道交通工程设计数字化管理平台研究与实践

针对当前城市轨道交通工程二、三维并行设计环境,本文通过分析研究BIM技术应用管理现状及面临的问题,提出以建设方为主导、总体总包设计单位统一管理的方式,研发基于云端技术的数字化管理平台。实践证明,基于数字化管理平台能够较好地实现轨道交通工程二、三维一体化协同设计及管理,有助于推动二维设计向三维设计方式的转变,具有一定的推广价值。

In situ formed Mg(BH_(4))_(2) for improving hydrolysis properties of MgH_(2)

The hydrolysis of MgH_(2) delivers high hydrogen capacity(15.2 wt%),which is very attractive for real-time hydrogen supply.However,the formation of a surface passivation Mg(OH)_(2) layer and the large excess of H_(2)O required to ensure complete hydrolysis are two key challenges for the MgH_(2) hydrolysis systems.Now,a low-cost method is reported to synthesize MgH_(2)@Mg(BH_(4))_(2) composite via ball-milling MgH_(2) with cheap and widely available B_(2)O_(3)(or B(OH)_(3)).By adding small amounts of B_(2)O_(3),the in-situ formed Mg(BH_(4))_(2) could significantly promote the hydrolysis of MgH_(2).In particular,the MgH_(2)–10 wt%B_(2)O_(3) composite releases 1330.7 mL·g^(−1) H_(2)(close to 80%theoretical hydrogen generation H_(2))in H_(2)O and 1520.4 mL·g^(−1) H_(2)(about 95%)in 0.5 M MgCl_(2) in 60 min at 26℃ with hydrolysis rate of 736.9 mL·g^(−1)·min^(−1) and 960.9 mL·g^(−1)·min^(−1) H_(2) during the first minute of the hydrolysis,respectively.In addition,the MgCl_(2) solution allows repeated use by filtering and exhibits high cycle stability(20 cycles),therefore leading to much reduced capacity loss caused by the excess H_(2)O.We show that by introducing B_(2)O_(3) and recycling the 0.5 M MgCl_(2) solution,the system hydrogen capacity can approach 5.9 wt%,providing a promising hydrogen generation scheme to supply hydrogen to the fuel cells.

The diagnostic value of tenascin-C in acute aortic syndrome

OBJECTIVES Misdiagnosis of acute aortic syndrome(AAS)significantly increases mortality.Tenascin-C(TN-C)is an extracellular matrix glycoprotein related to cardiovascular injury.The elevation of TN-C in AAS and whether it can discriminate suddenonset of acute chest pain in Chinese remains unclear.METHODS We measured the plasma concentration of TN-C by ELISA in a cohort of 376 patients with chest or back pain.Measures to discriminate AAS from acute coronary syndrome(ACS)were compared and calculated.RESULTS From October 2016 to September 2021,376 undiagnosed patients with chest or back pain were enrolled.166 of them were finally diagnosed as AAS,100 were ACS and 110 without cardiovascular diseases(NCV).TN-C was significantly elevated in AAS at 18.18 ng/mL(IQR:13.10–27.68)compared with 7.51 ng/mL(IQR:5.67–11.38)in ACS(P<0.001)and 3.68 ng/mL(IQR:2.50–5.29)in NCV(P<0.001).There was no significant difference in TN-C level among the subtypes of AAS.Of the 166 AAS patients,the peaked level of TN-C was at acute stage(P=0.012),then a slight of decrease was observed at subacute stage.The area under receiver operating characteristic curve for AAS patients versus NCV was 0.979(95%CI:0.964-0.994)for TN-C.At a cutoff level of 11.474 ng/mL,TN-C has a sensitivity of 76.0%,specificity of 85.5%,accuracy of 82.0%,positive predictive value(PPV)of 76.0%,negative predictive value(NPV)of 85.5%.Diagnostic performance of TN-C was superior to D-dimer and hs-cTnT.CONCLUSIONS The concentration of serum TN-C in AAS patients was significantly higher than that in ACS patients and NCV.TN-C could be a new biomarker to distinguish AAS patients in the early stage after symptoms onset from other pain diseases.

故宫“养心殿”和“三希堂”的名称一脉相承

三希堂和养心殿两个名称一脉相承,其寓意是宋儒心性义理的集中反映,是修养论的准确表达,亦是中国古代正统思想的传承。宋明理学的核心就是心性义理。“心即理也”,意思是本心即天理——世界的本源即“诚”,亦是“心”。理学名言:“宇宙便是吾心,吾心便是宇宙。”

Contents and Distribution of Petroleum Hydrocarbons (PHC) in Jiaozhou Bay Waters

Based on data from the investigation in Jiaozhou bay waters in 1979, the distribution, pollution source and seasonal variation of PHC in Jiaozhou Bay are analyzed. It is showed that in Jiaozhou bay PHC contents arrived the national Category Ⅱof the water quality standard during this year. In summer in the bay the pollution of PHC was heavy, while relatively light in spring. In the coastal waters in the east and the northeast of the bay, the PHC contents in spring surpassed the national Category Ⅱ, and surpassed the national Category Ⅲ. In the coastal waters, in the northeast of the bay, the change of the PHC contents formed the grads: the contents presented the falling trend from the big one to the small, which unveiled that the PHC souce in the bay mainly came from the discharge of the industrial waste water and living sewage.

Bone Auditory Thresholds Variations in Cholesteatoma Middle Ear Surgery

Objective: To investigate the changes of bone auditory thresholds variations in cholesteatoma middle ear surgery and its related factors and its related factors. Methods: 122 cases (122 ears) of unilateral cholesteatoma otitis media were treated by mastoidectomy and/or tympanoplasty plus stage I tympanoplasty, and tragus cartilage ring-cartilage membrane (Referred to as cartilage group, 62 ears) and temporalis muscle fascia (Referred to as fascia group, 60 ears) were used as tympanic membrane grafts respectively. The changes of bone conduction hearing threshold were compared between the two groups before and 1, 3, 6 months and 1, 3 years after operation. And compare the difference in the incidence of ossicular chain fixation or necrosis, vestibular window or cochlear window dysfunction between the two groups of patients with increased (positive) and decreased (negative) bone conduction threshold before operation. Results: Compared with the healthy side, 95 ears of 122 ears in the two groups had higher bone conduction hearing threshold before operation. Among them, 48 ears were in cartilage group and 47 ears were in fascia group;In 72 ears (76.34%) of these cases, the bone conduction hearing threshold decreased after operation, and the difference between the two groups was statistically significant (P Conclusion: The improvement of bone conduction hearing threshold in patients with cholesteatoma otitis media is mainly related to the fixation or necrosis of ossicular chain and the dysfunction of two windows. The tragus cartilage ring-perichondrium tympanoplasty can not only reduce the air-bone conduction difference, but also reduce the bone conduction hearing threshold, which has the advantage of stable and lasting hearing improvement.

基于RNA-based NGS检测非小细胞肺癌融合基因临床实践中国专家共识

基于RNA水平的二代测序(RNA-based next-generation sequencing, RNA-based NGS)技术已被非小细胞肺癌(non-small cell lung cancer, NSCLC)临床实践指南和专家共识推荐为融合基因的检测方法之一。NSCLC可用药靶点主要包括基因突变和融合,用于评估靶向治疗可行性的基因突变和融合基因检测均不可或缺。目前,基于DNA水平的NGS(DNA-based NGS)结合RNA-based NGS一次性同步检测基因突变和融合的技术已部分应用于临床实践。然而,RNA-based NGS检测融合基因的应用时机、应用场景和质控方面在我国仍缺乏规范和标准。本共识将进一步明确RNA-based NGS在融合基因检测中的应用时机、应用场景和质控,并给予指导性建议,推动RNA-based NGS在NSCLC临床诊疗中的应用,使患者能够最大程度地从融合基因检测中获益。

基于生成式对抗网络的自监督多元时间序列异常检测方法

异常检测是数据挖掘的重要研究方向之一.工业设备的各项指标以多元时间序列的形式被传感器监测,多元时间序列的异常检测对保障安全和提高服务质量至关重要,但是异常的定义相对模糊,具有异常标签的数据很稀少.此外,多元时间序列具有复杂的时间依赖性和随机性,使异常检测存在许多问题.提出CPCGAN模型,使用自监督学习的方法对多元时序数据进行异常检测.首先使用对比学习的方法得到多元时序数据的表示向量,再将具有先验信息的表示向量作为输入用来训练生成式对抗网络,通过生成式对抗网络的重构误差来确定异常.在五个数据集上与五种无监督异常检测方法进行对比,实验结果证明提出的方法能有效地检测两类异常,并且,在大多数数据集上的表现更好.

Antihepatoma peptide,scolopentide,derived from the centipede scolopendra subspinipes mutilans

BACKGROUND Centipedes have been used to treat tumors for hundreds of years in China.However,current studies focus on antimicrobial and anticoagulation agents rather than tumors.The molecular identities of antihepatoma bioactive components in centipedes have not yet been extensively investigated.It is a challenge to isolate and characterize the effective components of centipedes due to limited peptide purification technologies for animal-derived medicines.AIM To purify,characterize,and synthesize the bioactive components with the strongest antihepatoma activity from centipedes and determine the antihepatoma mechanism.METHODS An antihepatoma peptide(scolopentide)was isolated and identified from the centipede scolopendra subspinipes mutilans using a combination of enzymatic hydrolysis,a Sephadex G-25 column,and two steps of high-performance liquid chromatography(HPLC).Additionally,the CCK8 assay was used to select the extracted fraction with the strongest antihepatoma activity.The molecular weight of the extracted scolopentide was characterized by quadrupole time of flight mass spectrometry(QTOF MS),and the sequence was matched by using the Mascot search engine.Based on the sequence and molecular weight,scolopentide was synthesized using solid-phase peptide synthesis methods.The synthetic scolopentide was confirmed by MS and HPLC.The antineoplastic effect of extracted scolopentide was confirmed by CCK8 assay and morphological changes again in vitro.The antihepatoma effect of synthetic scolopentide was assessed by the CCK8 assay and Hoechst staining in vitro and tumor volume and tumor weight in vivo.In the tumor xenograft experiments,qualified model mice(male 5-week-old BALB/c nude mice)were randomly divided into 2 groups(n=6):The scolopentide group(0.15 mL/d,via intraperitoneal injection of synthetic scolopentide,500 mg/kg/d)and the vehicle group(0.15 mL/d,via intraperitoneal injection of normal saline).The mice were euthanized by cervical dislocation after 14 d of continuous treatment.Mechanistically,flow cytometry was conducted to evaluate the apoptosis rate of HepG2 cells after treatment with extracted scolopentide in vitro.A Hoechst staining assay was also used to observe apoptosis in HepG2 cells after treatment with synthetic scolopentide in vitro.CCK8 assays and morphological changes were used to compare the cytotoxicity of synthetic scolopentide to liver cancer cells and normal liver cells in vitro.Molecular docking was performed to clarify whether scolopentide tightly bound to death receptor 4(DR4)and DR5.qRT-PCR was used to measure the mRNA expression of DR4,DR5,fas-associated death domain protein(FADD),Caspase-8,Caspase-3,cytochrome c(Cyto-C),B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),x-chromosome linked inhibitor-of-apoptosis protein and Cellular fas-associated death domain-like interleukin-1βconverting enzyme inhibitory protein in hepatocarcinoma subcutaneous xenograft tumors from mice.Western blot assays were used to measure the protein expression of DR4,DR5,FADD,Caspase-8,Caspase-3,and Cyto-C in the tumor tissues.The reactive oxygen species(ROS)of tumor tissues were tested.RESULTS In the process of purification,characterization and synthesis of scolopentide,the optimal enzymatic hydrolysis conditions(extract ratio:5.86%,IC_(50):0.310 mg/mL)were as follows:Trypsin at 0.1 g(300 U/g,centipede-trypsin ratio of 20:1),enzymolysis temperature of 46°C,and enzymolysis time of 4 h,which was superior to freeze-thawing with liquid nitrogen(IC_(50):3.07 mg/mL).A peptide with the strongest antihepatoma activity(scolopentide)was further purified through a Sephadex G-25 column(obtained A2)and two steps of HPLC(obtained B5 and C3).The molecular weight of the extracted scolopentide was 1018.997 Da,and the peptide sequence was RAQNHYCK,as characterized by QTOF MS and Mascot.Scolopentide was synthesized in vitro with a qualified molecular weight(1018.8 Da)and purity(98.014%),which was characterized by MS and HPLC.Extracted scolopentide still had an antineoplastic effect in vitro,which inhibited the proliferation of Eca-109(IC_(50):76.27μg/mL),HepG2(IC_(50):22.06μg/mL),and A549(IC_(50):35.13μg/mL)cells,especially HepG2 cells.Synthetic scolopentide inhibited the proliferation of HepG2 cells(treated 6,12,and 24 h)in a concentration-dependent manner in vitro,and the inhibitory effects were the strongest at 12 h(IC_(50):208.11μg/mL).Synthetic scolopentide also inhibited the tumor volume(Vehicle vs Scolopentide,P=0.0003)and weight(Vehicle vs Scolopentide,P=0.0022)in the tumor xenograft experiment.Mechanistically,flow cytometry suggested that the apoptosis ratios of HepG2 cells after treatment with extracted scolopentide were 5.01%(0μg/mL),12.13%(10μg/mL),16.52%(20μg/mL),and 23.20%(40μg/mL).Hoechst staining revealed apoptosis in HepG2 cells after treatment with synthetic scolopentide in vitro.The CCK8 assay and morphological changes indicated that synthetic scolopentide was cytotoxic and was significantly stronger in HepG2 cells than in L02 cells.Molecular docking suggested that scolopentide tightly bound to DR4 and DR5,and the binding free energies were-10.4 kcal/mol and-7.1 kcal/mol,respectively.In subcutaneous xenograft tumors from mice,quantitative real-time polymerase chain reaction and western blotting suggested that scolopentide activated DR4 and DR5 and induced apoptosis in SMMC-7721 Liver cancer cells by promoting the expression of FADD,caspase-8 and caspase-3 through a mitochondria-independent pathway.CONCLUSION Scolopentide,an antihepatoma peptide purified from centipedes,may inspire new antihepatoma agents.Scolopentide activates DR4 and DR5 and induces apoptosis in liver cancer cells through a mitochondria-independent pathway.

复杂条件下盾构施工BIM管理平台研发及应用——以大连地铁5号线海底隧道工程为例

为解决在地质条件差、周边风险源高度敏感、施工工艺复杂、安全隐患探知难且处理难等复杂条件下存在的盾构隧道施工风险大、施工进度慢、前期处置费用高等问题,从BIM模型、生产管理信息等以GIS为骨架,多源异构的静动态数据融合形成时空整体,盾构机PLC、智能监测仪器等多源安全风险数据集成,二三维关联快速定位,实际进度与形象进度实时对比综合分析进度异常原因并辅助决策,材料用量异常结合地质状况分析等方面进行关键技术研究。采用WebGL三维引擎、Spring Cloud微服务架构、AVUE前端、Redis数据缓存,自研一键转换发布工具、系统集成综合框架、快速开发平台等研发盾构施工BIM管理平台,并在国内首例大直径穿越岩溶强烈发育区的“超级穿海”工程——大连地铁5号线火梭区间海底盾构隧道工程中成功实践应用,实现了盾构施工安全风险管控、质量巡检定位与二三维关联跟踪处理、进度对比辅助决策、成本异常溯源与分析等目标,保障了盾构施工安全洞通,提升了工程质量,缩短工期72 d,节省成本5%,有效提升了盾构隧道施工的数字化、信息化、可视化管理水平,为复杂条件下盾构隧道施工管理探索出可行的数字技术路线。

Mineralization of the Liwu large-scale stratiform copper deposits in Sichuan Province, China: Constraints from fluid inclusions

The Liwu stratiform copper deposit is located in the northwestern Jianglang dome,western China.Current studies mainly focus on the genetic type and mineralization of this deposit.Detailed fluid inclusion characteristics of metallogenic period quartz veins were studied to reveal the ore-forming fluid features.Laser Raman analysis indicates that the ore-forming fluids is a H_(2)O-NaCl-CH_(4)(-CO_(2))system.Fluid inclusions microthermometry shows a homogenization temperature of 181-375°C and a salinity of 5.26%-16.99%for the disseminated-banded Cu-Zn mineralization;but a homogenization temperature of 142-343°C and a salinity of 5.41%-21.19%for the massive-veined Cu-Zn mineralization.These features suggest a medium-high temperature and a medium salinity for the ore-forming fluids.H-O isotopic data indicates that the ore-forming fluids were mainly from the metamorphic and magmatic water,plus minor formation water.And sulfur isotopic data indicates that sulfur was mainly derived from the formation and magmatic rocks.Metallogenesis of the disseminated-banded mineralization was mainly correlated with fluid mixing and water-rock reaction;whereas that of the massive-veined mineralization was mainly correlated with fluid boiling.The genetic type of the deposit is a medium-high temperature hydrothermal deposit related to magmatism and controlled by shear zones.This study is beneficial to understand the stratiform copper deposit.

Proteome-wide identification of S-sulfenylated cysteines response to salt stress in Brassica napus root

Reactive oxygen species(ROS)play a key role in a variety of biological processes,such as the perception of abiotic stress,the integration of different environmental signals,and the activation of stress response networks.Salt stress could induce an increased ROS accumulation in plants,disrupting intracellular redox homeostasis,leading to posttranslational modifications(PTMs)of specific proteins,and eventually causing adaptive changes in metabolism.Here,we performed an iodoTMT-based proteomic approach to identify the sulfenylated proteins in B.napus root responsing to salt stress.Totally,1348 sulfenylated sites in 751 proteins were identified and these proteins were widely existed in different cell compartments and processes.Our study revealed that proteins with changed abundance and sulfenylation level in B.napus root under salt stress were mainly enriched in the biological processes of ion binding,glycolysis,ATP binding,and oxidative stress response.This study displays a landscape of sulfenylated proteins response to salt stress in B.napus root and provides some theoretical support for further understanding of the molecular mechanisms of redox regulation under salt stress in plants.

Pregnancy-Induced Changes in Ocular Biomechanics Are Related to Maternal Hormone Levels in Healthy Chinese Pregnant Women

Background: To explore the changes in ocular biomechanics during pregnancy and the postpartum period and their association with maternal hormone level changes. Methods: In a prospective cohort study, 24 eyes of 12 pregnant women were enrolled and monitored throughout pregnancy and after delivery (6 weeks). Intraocular pressure (IOP), central corneal thickness (CCT), corneal endothelium cell (CEC), axial length (AL), corneal curvature (K1, K2), anterior chamber depth (ACD), central subfield thickness (CST), macular volume (MV), cube average thickness (CAT), retinal nerve fibre layer (RNFL), tear meniscus height (TMH), and breaking up time (BUT) were measured throughout pregnancy, and blood plasma levels of maternal hormones were determined at the same time points. Results: A gradual decrease in IOP values was observed as gestation progressed, and there was a statistically significant difference in IOP between the 3rd trimester and the 1st and 2nd trimester and postpartum (p = 0.002, p = 0.006, p = 0.050). There was a significant difference between the 1st and 2nd trimesters in terms of MV (p = 0.023). The difference in RNFL in the 3rd trimester and postpartum was significant (p = 0.011). The levels of the β-hCG showed a significant correlation with K2, ACD, and TMH only in the 2nd trimester (r = 0.588, p = 0.045;r = - 0.740, p = 0.006;r = 0.642, p = 0.024). Regarding luteinizing hormone, there was a negative correlation with MV in the 1st and 2nd trimesters (r = - 0.598, p = 0.040;r = - 0.672, p = 0.017) and CAT in the 1st and 2nd trimesters (r = - 0.599, p = 0.040;r = - 0.655, p = 0.021). Luteinizing hormone levels were correlated with ACD (r = - 0.702, p = 0.011) in the 2nd trimester and K2 (r = 0.585, p = 0.046) in the 3rd trimester. A correlation was found between follicle-stimulating hormone levels and CEC, MV and CAT in the 1st trimester (r = - 0.677, p = 0.016;r = - 0.602, p = 0.039;r = - 0.584, p = 0.046) and AL in the 3rd trimester (r = - 0.618, p = 0.032). The correlation between oestradiol and CST in the 1st trimester (r = - 0.621, p = 0.031) and RNFL (r = 0.594, p = 0.041) in the postpartum. A statistically significant correlation between progesterone and MV (r = 0.583, p = 0.047) and TMH (r = 0.762, p = 0.004) was observed in the 1st trimester. No significant intergroup correlation was observed postpartum (p > 0.05). Conclusion: Ophthalmological parameters showed physiological changes induced by hormone levels in pregnancy and returned to baseline levels after delivery.

术前恶性不除外手术病理确诊肺部良性病变297例患者临床-放射-病理特征分析:一项中国单中心回顾性队列研究

背景与目的随着癌症早筛意识的提高,低剂量计算机断层扫描(low-dose computed tomography,LDCT)用于肺癌筛查在中国广泛开展。尽管有部分胸部LDCT筛查所见的肺部病灶是肿瘤病灶,但大多数的肺部结节是良性病变。如何有效的对肺部病灶进行术前鉴别,如何降低部分可避免手术的良性疾病的手术切除比例,是需要关注的问题。方法本研究纳入2017年1月1日-2018年12月31日期间北京协和医院诊治的,术前考虑肺部恶性病变不能除外,经手术病理确认为良性病变的患者,回顾性分析患者临床信息。结果 297例患者纳入本研究,占我院肺部病灶行肺部手术治疗患者的9.8%。197例(66.3%)患者因体检行LDCT筛查发现肺部病灶。肺部病变胸部CT影像学评估情况,可评估的323个病灶,平均长径为(17.9±12.1)mm,直径≥8 mm的占91.0%,实性最多见(212/323, 65.6%),此类肺部病灶可有毛刺征(71/323, 22.0%)、分叶征(94/323, 29.1%)、胸膜牵拉征(81/323, 25.1%)、血管集束征(130/323, 40.2%)、空泡征(23/323, 7.1%)等,提示恶性病变的影像学特征。292例(98.3%)行电视辅助胸腔镜手术(video-assisted thoracoscopic surgery, VATS),232例(78.1%)患者行肺楔形切除术,13例(4.4%)行肺段切除术,51例(17.2%)患者行肺叶切除术。4例(1.3%)患者出现手术并发症。术后病理类型前3位的是感染性疾病98例(33.0%)、炎性结节96例(32.3%)和错构瘤64例(21.5%)。结论因术前不能排除恶性而行手术切除的肺部良性病灶,影像学表现以实性病灶多见,但多具有提示恶性的影像学特征。VATS可作为一种明确病原病理的重要活检方式。此类病灶病理结果以感染性疾病和炎性结节最为常见,错构瘤第三。

洛拉替尼特殊不良反应管理中国专家共识

间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)融合基因是非小细胞肺癌(non-small cell lung cancer,NSCLC)中第二常见的肿瘤驱动基因。作为新型的第三代ALK酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI),洛拉替尼对多种ALK激酶域突变具有广谱且高效的临床活性,并具有强大的穿透血脑屏障效力。洛拉替尼的总体耐受性良好,其独特的不良反应或不良事件包括高脂血症与中枢神经系统反应等,多为轻至中度,通常经剂量调整和/或标准医疗干预即可管理。对于ALK阳性晚期NSCLC,开始洛拉替尼治疗前应充分评估患者基线特征与既往用药状况,预先告知患者可能经历的用药相关不良反应,并定期监测以实现药物临床获益的最大化。同时,多学科专家团队对于建立全面的诊断和治疗策略是至关重要的。

GSA:组学原始数据归档库

生命科学的发展已进入组学大数据时代,然而我国至今尚未形成公共数据库存储体系。为弥补国内空白,组学原始数据归档库(Genome Sequence Archive, GSA, http://bigd.big.ac.cn/gsa)系统遵循国际核苷酸序列数据联盟(International Nucleotide Sequence Database Collaboration,INSDC)相关数据库建设标准,广泛收集各类生命组学原始数据。自2015年底上线运行以来,已获得了包括Cell、Nature、PNAS、GPB等30余个国内外期刊的认可,收录的数据量呈显著增长趋势,提供的数据服务受到国内外广大科研人员的认可。GSA有效缓解了当前我国生命组学数据汇交、存储与共享困难的问题,为我国国家生物信息中心的建设奠定了坚实基础。本文对目前GSA数据汇交、审核、发布与管理等机制进行了深入阐述,以方便用户了解GSA的各项功能,提供更高效的数据服务。

急性冠状动脉综合征患者外周血β2整合素和Fractalkine的表达水平及机制研究

目的观察急性冠状动脉综合征(ACS)患者外周血中β2整合素和Fractalkine的表达水平并探讨其作用机制。方法选取襄阳市中心医院收治的86例ACS患者,其中不稳定型心绞痛(UA)32例,急性心肌梗死(AMI)54例,并以20例冠状动脉造影正常的患者和28例稳定型心绞痛(SAP)作为对照。采用流式细胞技术检测外周血白细胞中的β2整合素[LFA-1(CD11a/CD18)和Mac-1(CD11b/CD18)]阳性细胞百分率,酶联免疫吸附法检测血清中Fractalkine、ICAM-1的水平,Western blotting检测外周血白细胞中FAK、PKB蛋白表达水平。结果 AMI组和UA组患者外周血白细胞中LFA-1、Mac-1阳性细胞百分率和FAK、PKB蛋白水平高于正常组和SAP组患者(P<0.05)。冠状动脉粥样硬化性心脏病患者血清中Fractalkine、ICAM-1水平较冠状动脉造影正常的患者升高(P<0.05)。AMI组患者血清中Fractalkine、ICAM-1的水平高于正常组、UA组及SAP组患者(P <0.05)。结论 ACS时外周循环中Fractalkine释放增加,与白细胞表面的受体结合促进β2整合素及黏附分子活化,激活FAK-PI3K/PKB信号通路参与ACS的炎症反应。

紫外/氯工艺中磺胺类药物的转化:机理和毒性评价

磺胺类药物(sulfonamides,SAs)是一种常用的抗菌药物,由于在水生环境中经常被发现,因此备受关注。本文研究了紫外/氯(UV/Cl)工艺中3种磺胺类药物的转化过程及其产物毒性变化,并与氯化、紫外/过氧化氢(UV/H_(2)O_(2))工艺进行比较。结果显示,磺胺类药物在UV/Cl工艺中转化效率最高,氯类自由基在其中起到关键作用。在不同pH条件下,磺胺类药物在UV/Cl工艺中的转化效率会随pH值的增加而降低,但在pH值接近pKa值时突然升高,推测该现象与反应活性成分和SAs形态的变化有关。此外,对转化产物毒性的进一步研究发现,UV/Cl工艺的转化产物毒性最低(发光菌抑制率为6.99%—12.06%),但是未能显著降低SAs原溶液的毒性,并且由于氯代产物的出现,磺胺噻唑在转化后表现出更高的毒性。

A Petrological, Geochemical, and Geochronological Study of Shuikou Ultrabasic Rock Mass in Wuding County, Yunnan Province, China

Geotectonically, the Shuikou ultrabasic-basic rock mass is located on the western margin of the Yangtze Platform. As revealed by field geological surveys, the Shuikou rock mass intrudes into the quartz sandstones of the Sinian Chengjiang Formation (Zac). It is dominated by pyroxenites and can be roughly divided into four lithofacies zones, namely gabbros at the outermost periphery and fine-, medium-, and coarse-grained pyroxenites from margin to center. With the transition from pyroxenites to gabbros, the Shuikou rock mass features gradual enrichment in silica and alkali overall, an increase in ΣREE and (La/Yb)N ratio, and a decrease in δEu values and Eu/Sm ratio, indicating that the Shuikou rock mass was formed from the continuous differentiation and crystallization of consanguineous magma and that low-degree partial melting occurred meanwhile. According to the U-Pb baddeleyite geochronology, the crystallization age of the Shuikou rock mass is 210.7 ± 3 Ma (MSWD = 1.01). Based on this, as well as the analysis of geochemical characteristics, the Shuikou rock mass occurred in a continental intraplate tensional environment, this is closely related to the activities of the Emeishan mantle plume during the same period.