Consumer Acceptance of an SMS-Assisted Smoking Cessation Intervention: A Multicountry Study

This study assesses smokers' perceptions, motivations, and intentions towards using an SMS-assisted smoking cessation intervention in Australia, France, and Mexico through an extended technology acceptance model with mediating variables. Data was collected through online surveys. Results show that perceived usefulness and vicarious innovativeness predict use intentions for all three countries. Perceived ease of use is significant only for Mexico. Subjective norms are significant only for Mexico and Australia. Perceived monetary value and perceived annoyance are significant mediating variables for all three countries, whereas perceived enjoyment is significant only for Mexico and Australia. These results contribute to theory and practice.     

基于表观遗传调控的肿瘤相关巨噬细胞极化和功能重塑：肿瘤治疗新策略

肿瘤相关巨噬细胞（TAM）在肿瘤发展、转移和治疗抵抗中扮演了关键角色。TAM包含两种可相互极化的类型：促炎、抑制肿瘤生长的M1型和抑炎、促进肿瘤进展的M2型。表观遗传机制在肿瘤微环境对TAM的功能塑造中的作用十分独特,主要介导极化相关信号通路、细胞因子、代谢酶、关键转录因子和MHC及其调控因子等功能基因的转录或转录后调控,从而决定TAM的极化状态和功能。因此,从表观调控入手抑制M2极化、促进M1极化,进而引起TAM功能重塑,已逐渐成为肿瘤治疗的一个新兴策略。通过鉴定TAM特异性及关键表观调节机制、开发靶向TAM的新型表观药物递送系统、有效联合其他抗肿瘤疗法等方式,可进一步提高基于表观遗传调控的靶向巨噬细胞治疗的特异性,降低不良反应,实现更理想的抗肿瘤效果。     

肿瘤相关巨噬细胞及CD8+/CD68+细胞比值是影响肺腺癌患者预后的独 立危险因素

目的：探讨CD68+ 肿瘤相关巨噬细胞（TAM）、CD8+ T 细胞、Foxp3+ Treg 细胞等在肺腺癌（LUAD）组织中浸润分布及 其与患者预后的关系。方法：收集2004 年9 月至2009 年4 月间在苏州大学附属第三医院手术切除的93 例LUAD 组织及78 例癌 旁组织,采用组织芯片（TMA）及多重免疫荧光（mIF）技术检测其中的免疫细胞浸润与分布,Wilcoxon 秩和检验比较癌与癌旁组 织、癌巢与间质中浸润水平的差异,χ2 检验分析其浸润水平及CD8+/CD68+细胞比值与临床病理特征的关系,Kaplan-Meier 法和 COX 模型分析影响患者OS 的潜在危险因素。结果：与癌旁组织比较,癌组织中CD68+ TAM、CD8+ T 细胞、Foxp3+ Treg 细胞浸润 水平均显著增加（均P<0.01）,间质CD68+ TAM、CD8+ T 细胞的浸润水平均显著高于癌巢（均P<0.01）。总CD68+ TAM、癌巢及间质 CD68+ TAM 浸润水平与淋巴结转移呈正向关联（均P<0.05）,癌巢CD68+ TAM 浸润水平与T 分期呈正向关联（P<0.05）,间质 CD68+ TAM 浸润水平与病理分级呈正向关联（P<0.05）;癌组织中CD8+/CD68+细胞比值与病理分级、淋巴结转移均呈负向关联（均 P<0.05）。Kaplan-Meier 生存分析显示,LUAD 组织中总CD68+ TAM、癌巢及间质CD68+ TAM 高浸润患者OS 均短于低浸润患者（P<0.05 或P<0.01）、癌组织中CD8+/CD68+细胞比值高患者OS 显著长于低比值患者（P<0.05）。多因素COX 模型分析示,LUAD 患者年龄、TNM 分期及癌组织中CD8+/CD68+ 细胞比值是影响患者预后的独立风险因素（P<0.05或P<0.01）。结论:高度浸润的 CD68+TAM与LUAD的进展、侵袭、转移和不良预后显著关联,而高CD8+/CD68+ 细胞比值是影响LUAD 患者OS 的独立保护因素。     

肝郁痰凝型乳腺增生症中西医治疗疗效观察

目的:观察分析中成药合用(加味逍遥丸+小金胶囊)、西药(他莫昔芬)、心理疏导三种方法治疗肝郁痰凝型乳腺增生症的临床疗效。方法:将120例患者随机分为三组,每组40例:A组中成药合用(加味逍遥丸+小金胶囊)治疗,B组西药(他莫昔芬)治疗,C组心理疏导治疗。治疗21d后比较三组疗效。结果:根据乳房疼痛及乳腺结节大小的分级变化确定疗效。A组总有效率为92.5%,B组总有效率为77.5%,C组总有效率为57.5%。三组比较,P值均<0.01,差异有显著性差异。结论:中成药合用(加味逍遥丸+小金胶囊)治疗肝郁痰凝型乳腺增生症,比他莫昔芬、单纯心理疏导起效快,疗效显著,毒副作用少,值得临床推广应用。     

Tumor-associated macrophages as potential diagnostic and prognostic biomarkers in breast cancer

Breast cancer development largely depends upon the essential contributions from the tumor microenvironment, where several inflammatory cell populations (e.g. macrophages) orchestrate breast cancer development. The majority of tumor-associated macrophages (TAMs) exhibit alternatively activated M2 properties, produce abundant anti-inflammatory factors and facilitate tumor development. Clinical evidences compellingly indicate the association between high TAMs influx and poor prognosis in patients with breast cancers. The pan-macrophage marker CD68 is now generally utilized to identify TAMs in diagnostic biopsy samples, and some other TAM-related biomarkers are also utilized in prognosis prediction, including CD163, vascular endothelial growth factor (VEGF), hypoxia-inducible factors (HIFs), proliferating cellular nuclear antigen (PCNA), ferritin light chain (FTL) and C–C motif chemokine ligand 18 (CCL18). In this review, we highlight the recent progress made in understanding the relationship between TAMs and clinicopathological parameters in human breast cancer and address the potential value of TAMs as diagnostic and prognostic biomarkers.     

Iron levels in polarized macrophages: Regulation of immunity and autoimmunity

Although the hallmark of autoimmune diseases remains the generation of autoantigen-specific lynfocytic cell response, growing evidence is showing a key role for macrophages in a number of autoimmune diseases. Macrophages are characterized by phenotypical and functional heterogeneity. Different immunological signals, coming from systemic blood circulation or from microenvironment, polarize macrophages to classical (M1) or alternative (M2) phenotypes. Iron accumulation in M1 macrophages is a well known bacteriostatic mechanism and one of the mechanisms at the basis of anemia associated to chronic inflammation. Moreover, some recent data suggest that iron accumulation in macrophages can directly activate macrophages to pro-inflammatory M1 phenotype, highlighting a putative role of macrophage iron retention in the pathogenesis of chronic inflammatory and autoimmune diseases. Conversely, iron content is low in M2 macrophages, principally due to increased iron release, and increased availability of iron in the extracellular milieu supported by M2 macrophages could influence the growth rate of adjacent cell and thus play an important role in tumor growth and tissue remodeling. In this review we summarize the molecular mechanisms sustaining differential iron metabolism in polarized macrophages, discuss the relevance of this metabolic signature in chronic inflammatory and autoimmune diseases, and finally focus on potential therapeutic implications rising from a better understanding of underlying molecular mechanisms.     

金属夹板外固定与可吸收骨锚系统治疗早期闭合性锤状指

背景：可吸收骨锚治疗锤状指是一种新型的内固定方法。 目的：比较金属夹板外固定与可吸收骨锚系统治疗早期闭合性锤状指病例的临床效果。 方法：早期闭合性锤状指病例40例,其中采用金属夹板外固定治疗24例,采用可吸收骨锚内固定治疗16例,受伤至给予治疗时间均为1周以内。对两组患者临床资料及手术结果进行回顾性分析,并对两组的优良率进行统计学分析。 结果与结论：所有病例均获得随访4个月以上,最长随访时间14个月。参照国际手外科学会推荐的TAM系统评定法,金属夹板外固定组优良率66.7%;可吸收骨锚内固定组优良率93.8%,两组间差异有显著性意义(P < 0.05),金属夹板固定组有2例分别于治疗后4个月,6个月出现复发;骨锚组有1例功能锻炼时出现局部肿痛、皮肤发红,经物理治疗后好转,表明可吸收骨锚内固定组的疗效显著优于金属夹板外固定组。可吸收骨锚系统治疗过程简单,效果肯定,是治疗早期闭合性锤状指的首选治疗方法,但其价格昂贵,未能广泛开展;金属夹板虽然操作简单,但是治疗过程中管理困难,复发率发高。     

Gas6 is complexed to the soluble tyrosine kinase receptor Axl in human blood

Summary. Background: The vitamin K‐dependent Gas6 protein (product of growth arrest specific gene 6) binds to, and activates the TAM receptor tyrosine kinases Tyro3, Axl and Mer. It has been suggested that Gas6 and the TAM receptors are important for primary platelet functions, but Gas6 cannot be found in human platelets. However, Gas6 is present in human plasma at a concentration of around 0.2 nM, which is a thousand‐fold lower than that of the homologous protein S. The Axl and Mer receptors can be cleaved close to the cell membrane, yielding soluble molecules consisting of the extracellular parts of the receptors. Objective: To investigate if soluble Axl (sAxl) is present in human serum and plasma and if Gas6 circulates in complex with sAxl. Methods: We expressed recombinant sAxl, raised antibodies and developed and validated an ELISA for Axl. Serum and plasma were analyzed using ELISAs for Gas6, Axl and sAxl–Gas6 complexes. Serum was gel filtered and fractions analyzed by the different ELISAs to determine if Gas6 in serum is free or complexed. Immunoprecipitation was used to investigate binding between Gas6 and sAxl in serum. Results: sAxl is present in serum and plasma at around 0.6 nM and all Gas6 is bound to sAxl. No complexes between Gas6 and the soluble forms of Mer and Tyro3 could be detected, indicating that sAxl is the physiological binder of Gas6 in human serum. Conclusions: Gas6 in circulation is bound to sAxl suggesting circulating Gas6 to be inhibited and incapable of stimulating the TAM receptors.     

Persistent restoration to the immunosupportive tumor microenvironment in glioblastoma by bevacizumab

Although vascular endothelial growth factor (VEGF) promotes the immunosuppressive microenvironment, the efficacy of bevacizumab (Bev) on tumor immunity has not been fully investigated. The present study used 47 glioblastoma tissues obtained at 3 different settings: tumors of initial resection (naïve Bev group), tumors resected following Bev therapy (effective Bev group), and recurrent tumors after Bev therapy (refractory Bev group). The paired samples of the initial and post‐Bev recurrent tumors from 9 patients were included. The expression of programmed cell death‐1 (PD‐1)/PD ligand‐1 (PD‐L1), CD3, CD8, Foxp3, and CD163 was analyzed by immunohistochemistry. The PD‐L1+ tumor cells significantly decreased in the effective or refractory Bev group compared with the naïve Bev group (P < .01 for each). The PD‐1+ cells significantly decreased in the effective or refractory Bev group compared with the naïve Bev group (P < .01 for each). The amount of CD3+ and CD8+ T cell infiltration increased in the refractory Bev group compared with the naïve Bev group (CD3, P < .01; CD8, P = .06). Both Foxp3+ regulatory T cells and CD163+ tumor‐associated macrophages significantly decreased in the effective or refractory Bev group compared with the naïve Bev group (Foxp3, P < .01 for each; CD163, P < .01 for each). These findings were largely confirmed by comparing paired initial and post‐Bev recurrent tumors. Bevacizumab restores the immunosupportive tumor microenvironment in glioblastomas, and this effect persists during long‐term Bev therapy.     

疏肝益肾法对乳腺癌术后内分泌治疗者雌二醇、孕酮及脂肪酸合成酶的影响

目的 观察疏肝益肾法对乳腺癌术后内分泌治疗患者血中雌二醇(E2)、孕酮(P)及脂肪酸合成酶(FAS)水平变化的影响.方法 采用随机、平行、同期手段,通过美国Abbott实验室注册的AXSYM系列实验方法检测疗前疗后血浆E2、P及FAS水平.结果 生化检测结果发现观察组与对照组及观察组治疗前后的血浆E2、P及FAS水平变化没有统计学意义,提示TAM的副作用与血浆E2、P及FAS水平无关.结论 由此推测还存其他与血浆激素水平浓度不直接相关的诱发乳腺癌途径.