Multi-Axis Attention With Convolution Parallel Block for Organoid Segmentation

Dear Editor,This letter presents an organoid segmentation model based on multi-axis attention with convolution parallel block.MACPNet adeptly captures dynamic dependencies within bright-field microscopy images,improving global modeling beyond conventional UNet.

樟叶胡椒中新木脂素成分的研究

自胡椒科胡椒属植物樟叶胡椒(Piper polysyphorum C. DC)中分离到六个新木脂素(neolignans)类化合物,经光谱(UV,IR,MS,~1H-NMR,^(13)C-NMR,2D-NMR,CD)分析及衍生物制备,确定Ⅱ为新化合物,即threo-△~7-7-羟基-3,4,5,3′,5′-五甲氧基-8-O-4′-新木脂素,为一对对映体,命名为樟叶素(polysyphorin),Ⅰ,Ⅲ,Ⅳ为新的对映体,分別为(+)-virolongin,(+)-grandisin及(+)-lancifolin D.化合物Ⅴ为南藤素(wallichinine),Ⅵ为山蒟素D(hancinone D)。血小板活化因子(PAF)受体结合实验及PAF引起的血小板聚集实验证明化合物Ⅰ～Ⅴ具有明显的抑制活性。

地血香中1个新的三萜类成分

<正> 地血香系五味子科植物异形南五味子[Kadsura heteroclita(Roxb)Craib]的根或藤茎,民间用于治疗风湿、胃及十二指肠溃疡等。已报道自同属植物分得具有当归酸侧链末端的羊毛甾烯型四环三萜类化合物——安五酸。我们在研究地血香化学成分中,分得化合物(Ⅰ),其光谱与安五酸的光谱相比较,UV、IR、MS、CD谱均相似,~1H

生物统计的研究进展与挑战

生物统计学是以解决生物学、医学、公共卫生学、农学等领域科学问题为目标的应用型学科,近年来在精准医疗的背景下得以快速发展。另一方面,生物统计研究面对的数据存在海量化、复杂化和异质化的大数据特征,对理论与应用研究者都提出了新的挑战。本文围绕生物统计研究中的流行病学研究、临床试验设计、生存数据分析和基因数据分析展开讨论,在介绍基本思路的基础上对最新挑战及前沿发展方向进行展望。

三硝基甲苯蛋白加合物及其结构鉴定

在三硝基甲苯(trinitrotoluene,TNT)的分布和排泄实验中。约90％的注入量于给药后3～4d排出体外,体内部分主要分布于血液和肝、肾组织,其中以血液中的含量最高,从血液中各组分含量测定看到血红蛋白部分占比例最高,且存留较久,提示TNT有以共价结合形式存在体内的可能,通过加合物的分离,提取和测定,首次证实TNT可与蛋白共价结合,在血液和肝组织中,分别约有20％和30％以加合物形式存在.进一步对所形成的血红蛋白及肝组织蛋白加合物水解,提取,净化,并经高效液相色谱对其结构进行了鉴定,证实提取液中的主要放射性是由TNT还原代谢产物2氨基-4,6-二硝基甲苯(2A)和4氨基-2,6-二硝基甲苯(4A)所构成,与体外制备血红蛋白加合物的结构相比,得到类似结果。

三硝基甲苯血红蛋白加合物作为生物监测的标志物

在前文已证实TNT进入体内可与蛋白共价结合的基础上,用[^(14)C]TNT法比较了TNT与血红蛋白、血浆蛋白及肝、肾组织蛋白四种蛋白加合物的共价结合,从加合物的剂量反应关系,在体内存留时间以及取样方便等条件来看,血红蛋白加合物是生物监测最有希望的指标,文中对它作为生物监测的意义进行了讨论。

帕博利珠单抗联合以铂类为基础的化疗治疗非小细胞肺癌合并稳定性脑转移患者的结局:KEYNOTE-021、-189和-407研究的汇总分析

背景与目的此项探索性分析回顾评价了晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的结局,旨在确定基线时合并脑转移是否会影响一线应用帕博利珠单抗联合化疗(pembrolizumab plus chemotherapy,PC)比对单用化疗的疗效。患者和方法对KEYNOTE-021队列G(非鳞癌)、KEYNOTE-189(非鳞癌)和KEYNOTE-407(鳞癌)三项研究晚期NSCLC患者的数据进行汇总分析。患者接受含铂两药化疗和/或35个周期帕博利珠单抗治疗(每3周200 mg)。所有研究均纳入了经治或初治的稳定性脑转移患者(KEYNOTE-189与KEYNOTE-407研究纳入初治脑转移患者)。经治的脑转移患者已处于病情稳定的状态≥2周(KEYNOTE-021队列G患者≥4周),无新发或脑转移病灶扩大的证据且入组前至少3天以上未使用激素。初治的无症状脑转移患者需定期接受脑部影像学检查。结果共纳入1298例患者,其中171例有基线脑转移,1127例无脑转移。两组的中位随访时间(范围)在数据截止时分别为10.9(0.1-35.1)个月和11.0(0.1-34.9)个月。合并脑转移和无脑转移患者的总生存期[0.48(95%CI:0.32-0.70)和0.63(95%CI:0.53-0.75)]和无进展生存期[0.44(95%CI:0.31-0.62)和0.55(95%CI:0.48-0.63)]的风险比(PC/化疗)相似。合并脑转移的患者中,PC组和单用化疗组患者的中位总生存期分别为18.8个月和7.6个月,中位无进展生存期分别为6.9个月和4.1个月。无论是否合并脑转移,PC组患者的客观缓解率都高于单用化疗组,且缓解持续时间有显著延长。合并脑转移的患者中,PC组与单用化疗组的治疗相关不良事件发生率分别为88.2%和82.8%;而无脑转移的患者中,两组治疗相关不良事件的发生率分别为94.5%和90.6%。结论无论是否合并脑转移,与单用化疗相比,帕博利珠单抗联合以铂类为基础的组织学特异性化疗可改善所有PD-L1亚组的临床结局,其中包括PD-L1肿瘤比例评分<1%的患者,并且在晚期NSCLC患者中安全性良好。该方案是晚期NSCLC初治患者的标准方案,并可用于合并稳定性脑转移的患者。

Dibenzocyclooctadiene Lignans with Platelet-Activating Factor (PAF) Antagonist Activity from Kadsura heteroclita

Seven known dibenzocyclooctadiene lignans,tigloylgomisin P(1), angeloylgomisin P(2),gomisin A(3),Schizandrin(4),angeloylgomisin H(5),gomisin B(6) and R(+)-gomisin M_1(7)were isolated from Kadsura heteroclita.The conformation of tiglolylgomisin P(1)was established by 2D NMR techniques.Using[~3H]platelet activating factor(PAF)binding to human platelet membrane assay,(1),(2)and(7)showed PAF receptor antagonistic activities.

骨密度测量中精密度的重要性

骨密度测定 ,不论采取何特殊技术 ,即使严格地按照厂家建议的操作程序 ,也常常不能达到完美的重复性。必须确定每台骨密度仪不同骨骼部位的精确度。精密度 ,如标准差平均方根或变异系数平均方根 ,被用来确定骨密度的变化 ,即精密度决定最小显著性变化值和随访需要的至少时间间隔。除非确定了精密度 ,否则就不能确定任何水平的统计可信度最小显著性变化值 。

真实世界数据和证据在我国临床决策中的应用现状

传统上,循证医学理念下的临床决策通常以随机对照试验作为最佳临床证据。快速发展的真实世界数据和真实世界证据领域结合了真实临床环境的复杂性,为临床医生提供了补充性证据,并丰富了证据类别,以辅助临床医生做出更好的循证临床决策。本研究旨在梳理我国用于循证临床决策的真实世界数据和证据的范围和适用性,并总结潜在障碍和可行建议,以期进一步推进高质量真实世界数据和证据在循证临床决策中的可接受性。

Emodin induces apoptosis in human prostate cancer cell LNCaP

Aim： To elucidate effects and mechanisms of emodin in prostate cancer cells. Methods： Viability of emodin-treated LNCaP cells and PC-3 cells was measured by MTT assay. Following emodin treatments, DNA fragmentation was assayed by agarose gel electrophoresis. Apoptosis rate and the expression of Fas and FasL were assayed by flow cytometric analysis. The mRNA expression levels of androgen receptor （AR）, prostate-specific antigen （PSA）, p53, p21, Bcl-2, Bax, caspase-3, -8, -9 and Fas were detected by RT-PCR, and the protein expression levels of AR, p53 and p21 were detected by Western blot analysis. Results： In contrast to PC-3, emodin caused a marked increase in apoptosis and a decrease in cell proliferation in LNCaP cells. The expression of AR and PSA was decreased and the expression of p53 and p21 was increased as the emodin concentrations were increased. In the same time, emodin induced apoptosis of LNCaP cells through the upregulation of caspase-3 and -9, as well as the increase of Bax/Bcl-2 ratio. However, it did not involve modulation of Fas or caspase-8 protein expression. Conclusion： In prostate cancer cell line, LNCaP, emodin inhibites the proliferation by AR and p53-p21 pathways, and induces apoptosis via the mitochondrial pathway.

Targeting the PI3K-AKT-mTOR signaling network in cancer

The phosphoinositide 3-kinase-AKT-mammalian target of rapamycin (PI3K-AKT-mTOR) pathway is a frequently hyperactivated pathway in cancer and is important for tumor cell growth and survival. The development of targeted therapies against mTOR, a vital substrate along this pathway, led to the approval of allosteric inhibitors, including everolimus and temsirolimus, for the treatment of breast, renal, and pancreatic cancers. However, the suboptimal duration of response in unselected patients remains an unresolved issue. Numerous novel therapies against critical nodes of this pathway are therefore being actively investigated in the clinic in multiple tumour types. In this review, we focus on the progress of these agents in clinical development along with their biological rationale, the need of predictive biomarkers and various combination strategies, which will be useful in counteracting the mechanisms of resistance to this class of drugs.

TRAIL-induced apoptosis of hepatocellular carcinoma cells is augmented by targeted therapies

AIM:To analyze the effect of chemotherapeutic drugs and specific kinase inhibitors,in combination with the death receptor ligand tumor necrosis factor-related apoptosis inducing ligand(TRAIL),on overcoming TRAIL resistance in hepatocellular carcinoma(HCC)and to study the efficacy of agonistic TRAIL antibodies,as well as the commitment of antiapoptotic BCL-2 proteins, in TRAIL-induced apoptosis. METHODS:Surface expression of TRAIL receptors (TRAIL-R1-4)and expression levels of the antiapoptotic BCL-2 proteins MCL-1 and BCL-xL were analyzed by flow cytometry and Western blotting,respectively. Knock-down of MCL-1 and BCL-xL was performed by transfecting specific small interfering RNAs.HCC cellswere treated with kinase inhibitors and chemotherapeutic drugs.Apoptosis induction and cell viability were analyzed via flow cytometry and 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. RESULTS:TRAIL-R1 and-R2 were profoundly expressed on the HCC cell lines Huh7 and Hep-G2. However,treatment of Huh7 and Hep-G2 with TRAIL and agonistic antibodies only induced minor apoptosis rates.Apoptosis resistance towards TRAIL could be considerably reduced by adding the chemotherapeutic drugs 5-fluorouracil and doxorubicin as well as the kinase inhibitors LY294002[inhibition of phosphoinositol- 3-kinase(PI3K)],AG1478(epidermal growth factor receptor kinase),PD98059(MEK1),rapamycin(mam- malian target of rapamycin)and the multi-kinase inhibitor Sorafenib.Furthermore,the antiapoptotic BCL-2 proteins MCL-1 and BCL-xL play a major role in TRAIL resistance:knock-down by RNA interference increased TRAIL-induced apoptosis of HCC cells.Additionally, knock-down of MCL-1 and BCL-xL led to a significant sensitization of HCC cells towards inhibition of both c-Jun N-terminal kinase and PI3K.CONCLUSION:Our data identify the blockage of survival kinases,combination with chemotherapeutic drugs and targeting of antiapoptotic BCL-2 proteins as promising ways to overcome TRAIL resistance in HCC.

Preparation of Ternary Lanthanide Complexes with Unsaturated Acid and 1,10-Phenanthroline, and Their Anti-Inflammatory Action

Four ternary lanthanide complexes with unsaturated acid and 1,10-phenanthroline are prepared in methanol and characterized by elemental analysis, molar conductance, UV, IR, (()~1H) NMR and XPS. The results from this paper show that the complexes Ln(phen)(SA)_3·2H_2O or Ln(phen)(CA)_3·H_2O (Ln=Ce(Ⅲ), Sm(Ⅲ) and Eu(Ⅲ), (phen=1,10-)phenanthroline, SA=Sorbate and CA=Cinnamate) has better anti-inflammatory effect than cerium nitrate and their gremores are steadier than cerium nitrate gremor. And there is a kind of medicament which can replace the cerium nitrate gremor completely in treating burn.

云母/金属氧化物新型浅色导电颜料

浅色导电颜料的发展对导电颜料需求的原因是多方面的,导电颜料可在许多场合下应用,例如: 电子设备上使用的防静电涂料; 塑料箱罩上使用的电磁屏蔽涂料; 抗静电地板涂料;

Development of a physiologically relevant dripping analytical method using simulated nasal mucus for nasal spray formulation analysis

Current methods for nasal spray formulations have been elementary evaluating the dripping characteristics of a formulation and have not assessed the behavior of the nasal formulation in the presence of varying types of mucus depending on the indication or diseased state. This research investigated the effects of nasal mucus on the dripping behavior of nasal formulations and focused on developing an improved in vitro analytical test method that is more physiologically relevant in characterizing nasal formulation dripping behavior. Method development was performed using simulated nasal mucus preparations for both healthy and diseased states as coatings for the dripping experiment representing a wide range of viscosity. Factors evaluated during development of this in vitro test method included amount of mucus, application of mucus, drying times, and compatibility of the mucus on a C18 Thin Layer Chromatography(TLC) substrate. The dripping behavior of nasal formulations containing a range of 1%Avicel to 3.5% Avicel was assessed by actuating the nasal spray on a perpendicular TLC plate coated with either healthy or diseased simulated nasal mucus. After actuation of the nasal spray, the dripping of the formulation on the coated TLC plate was measured after the plate was repositioned vertically. The method that was developed generated reproducible results on the dripping behavior of nasal formulations and provided critical information about the compatibility of the formulation with the nasal mucus for different diseased states, aiding in nasal spray formulation development and physical characterization of the nasal spray.

Bcl-x_L and Myeloid cell leukaemia-1 contribute to apoptosis resistance of colorectal cancer cells

AIM： TO explore the role of Bcl-XL and Myeloid cell leukaemia （Mcl）-I for the apoptosis resistance of colorectal carcinoma （CRC） cells towards current treatment modalities. METHODS： Bcl-XL and Mcl-1 mRNA and protein expression were analyzed in CRC cell lines as well as human CRC tissue by Western blot, quantitative PCRand immunohistochemistry. Bcl-XL and Mcl-1 protein expression was knocked down or increased in CRC cell lines by applying specific siRNAs or expression plasmids, respectively. After modulation of protein expression, CRC cells were treated with chemotherapeutic agents, an antagonistic epidermal growth factor receptor （EGFR1） antibody, an EGFR1 tyrosine kinase inhibitor, or with the death receptor ligand TRAIL. Apoptosis induction and cell viability were analyzed. RESULTS： Here we show that in human CRC tissue and various CRC cell lines both Bcl-xL and Mcl-1 are expressed. Bcl-xL expression was higher in CRC tissue than in surrounding non-malignant tissue, both on protein and mRNA level. Mcl-1 mRNA expression was significantly lower in malignant tissues. However, protein expression was slightly higher. Viability rates of CRC cells were significantly decreased after knock down of Bcl-xL expression, and, to a lower extent, after knock down of Mcl-1 expression. Furthermore, cells with reduced Bcl-xL or Mcl-1 expression was more sensitive towards oxaliplatinand irinotecan-induced apoptosis, and in the case of Bcl-xL also towards 5-FU-induced apoptosis. On the other hand, upregulation of Bcl-xL by transfection of an expression plasmid decreased chemotherapeutic drug-induced apoptosis. EGF treatment clearly induced Bcl-xL and Mcl-1 expression in CRC cells. Apoptosis induction upon EGFR1 blockage by cetuximab or PD168393 was increased by inhibiting Mcl-1 and Bcl-xL expression. More strikingly, CD95- and TRAIL-induced apoptosis was increased by Bcl-xL knock down. CONCLUSION： Our data suggest that Bcl-xL and, to a lower extent, Mcl-1, are important anti-apoptotic factors in CRC. Specific downregulation of Bcl-xL is a promising approach to sensitize CRC cells towards chemotherapy and targeted therapy.

狭义相对论的逻辑不自洽问题和新伽利略时空观

科学理论需要在逻辑上自洽。分析了狭义相对论对高速运动的不稳定微观粒子寿命延长的解释,发现狭义相对论的解释否定了光速不变原理或相对论性时空观。进一步分析发现,在狭义相对论“时间膨胀”和“长度收缩”的推导过程中,观察系和被观察系的指定完全相反。这一现象说明“时间膨胀”和“长度收缩”不是狭义相对论的逻辑结果,狭义相对论的逻辑结论应该是“时间收缩”和“长度收缩”(或“时间膨胀”和“长度膨胀”)。在狭义相对论的理论框架内不能正确地推导出运动物体的横质量,在狭义相对论的框架内得出正确横质量公式的推导都存在逻辑或物理错误。因此,狭义相对论在逻辑上是不自洽的,相对论性时空观没有实验证据。现代物理学应该建立在以局部优势引力场为相对优越参照系的新伽利略时空观的基础上。从光传播媒介对应于局部优势引力场这一原则出发,解释了迈克尔逊-莫雷实验、菲索流水光速实验和光行差现象。“运动质量”可由运动物体在受电磁场或引力场作用时受力的大小与该物体的运动速度有关得到解释。不稳定粒子寿命和物理时钟受各自的运动状态影响,也可以分别由粒子衰变和物理时钟依赖的具体物理过程受其相对于局部优势引力场的运动状态的影响来解释。

Development and validation of a GC–FID method for quantitative analysis of oleic acid and related fatty acids

Oleic acid is a common pharmaceutical excipient that has been widely used in various dosage forms. Gas chromatography （GC） has often been used as the quantitation method for fatty acids normally requiring a derivatization step. The aim of this study was to develop a simple, robust, and derivatization-free GC method that is suitable for routine analysis of all the major components in oleic acid USP-NF （United States Pharmacopeia-National Formulary） material. A gas chromatography-flame ionization detection （GC-FID） method was developed for direct quantitative analysis of oleic acid and related fatty acids in oleic acid USP-NF material. Fifteen fatty acids were separated using a DB-FFAP （nitroterephthalic acid modified polyethylene glycol） capillary GC column （30 m × 0.32 mm i.d.） with a total run time of 20 rain. The method was validated in terms of specificity, linearity, precision, accuracy, sensitivity, and robust- ness. The method can be routinely used for the purpose of oleic acid USP-NF material analysis.