Tumor’host interaction in the optimization of paclitaxel-based combination therapies with vascular targeting compounds

Targeting of the tumor stroma, including the tumor vasculature, represents a new frontier in the treatment of malignancy. Preclinical studies and clinical experiences have established that stroma-directed novel agents must be combined with conventional therapies in order to achieve relevant therapeutic efficacy. Here we review our preclinical experience on combinations of paclitaxel with a tyrosine kinase receptor inhibitor of angiogenesis (SU6668) and a vascular disrupting agent (VDA, ZD6126), and discuss the critical factors that determine the outcome of these treatments. We also analyze the relevance of the intrinsic sensitivity of the tumor to the drugs, as well as the possibility that the two combined agents synergistically affect the vasculature or independently target the host and the tumor compartments. Finally, we discuss the need to carefully optimize scheduling and sequencing, through the use of reliable end points, in order to avoid negative pharmacological interactions and to improve the antineoplastic efficacy of paclitaxel-based combination treatments.     

Spinal cord stimulation for the treatment of pain and toe ulceration associated with systemic sclerosis: a case report

Systemic sclerosis is a complex disease characterized by extensive fibrosis, microvascular alterations, and additional sequelae. Microvascular alterations can cause painful ulcers and necrosis; however, conservative or surgical treatment is often challenging in terms of healing. The study aimed to describe a toe ulcer with systemic sclerosis and its’ successful treatment with spinal cord stimulation. An 83-year-old woman, who was diagnosed with systemic sclerosis over the past decade, was distressed by a non-healing toe ulcer for an extended period of time. The patient underwent spinal cord stimulation treatment with the expectation of pain relief and an improvement in microcirculatory insufficiency. Her pain scales and microcirculation improved, and the toe ulcer healed. Furthermore, the frequency of Raynaud’s symptoms was reduced, and the patient’s pain decreased. There was no recurrence of the ulcer and she no longer needed a cane for walking.     

复方生地合剂治疗系统性红斑狼疮（阴虚内热型）的有效性与安全性评价

目的：评价复方生地合剂治疗阴虚内热型系统性红斑狼疮（SLE）的临床疗效及其安全性。方at：选择阴虚内热型SLE患者65例,随机分为治疗组31例和对照组34例。两组均以糖皮质激素作为基础用药,治疗组给予复方生地合剂,对照组给予硫酸羟基氯喹治疗,疗程12周。观察两组的临床疗效、系统性红斑狼疮疾病活动指数（SLEDAI）、免疫学指标及安全性指标。结果：治疗后,治疗组和对照组的总有效率分别为60．0％和56．7％,两组比较差异无统计学意义（P〉0．05）。治疗后,两组患者的SLEDAI、抗ds-DNA水平均显著降低（P〈0．01,P〈0．05）,但两组比较差异无统计学意义（P〉0．05）。治疗过程中,治疗组和对照组的不良反应事件发生率分别为10．0％和34．3％,治疗组明显低于对照组（P〈0．05）。结论：复方生地合剂对SLE有一定的免疫抑制作用,且能降低SLE的活动度,毒副反应较少。     

DRESS syndrome: a detailed insight

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a serious and potentially fatal adverse effect to therapeutic medications. The incidence of this condition varies among different ethnicities because of the difference in the genetic makeup. Though fever, rash and eosinophilia are essential features for the diagnosis of this syndrome, these vary from patient to patient along with the involvement of various organs such as liver, kidney, lungs, pancreas, etc. Some of the atypical features are dysphagia, agranulocytosis, and chylous ascites. Phenytoin, phenobarbitone, carbamazepine, and allopurinol are the most common drugs responsible for developing this syndrome, although the list is fairly long. Among the criteria used for the diagnosis of DRESS syndrome, European Registry of Severe Cutaneous Adverse Reactions to Drugs and Collection of Biological Samples (RegiSCAR) criteria is the most commonly used one. The management of this syndrome involves early removal of the causative agent and treatment with anti-histamines and emollients in the mild form, corticosteroids in the moderate form and plasmapheresis in the severe form along with other alternatives drugs. Healthcare professionals should be more vigilant about the early manifestations of this syndrome, as early diagnosis and treatment improve outcomes considerably.     

Association of Dietary Inflammatory Potential with Blood Inflammation: The Prospective Markers on Mild Cognitive Impairment

Inflammation is known as an important mechanism of cognitive dysfunction. Systemic immune inflammation index (SII) and system inflammation response index (SIRI) are two blood inflammatory markers, which are related to many chronic diseases including cognitive impairment. It is recognized that dietary inflammatory index (DII), which is used to estimate the overall inflammatory potential of diet, may be related to mild cognitive impairment (MCI) as well. This study aimed to explore the relationship between SII, SIRI and DII, as well as the role of these inflammatory indexes on MCI in elderly people. A total of 1050 participants from Beijing were included. Neuropsychological tests were used for cognitive evaluation. Energy-adjusted DII scores were calculated based on semi-quantitative food frequency questionnaire. Blood samples were tested for calculating SII and SIRI. Log-binomial regression models were used to estimate the correlation of indexes. After adjusting demographic characteristics, SII and SIRI in MCI individuals were higher than controls (p ≤ 0.001). DII, SII and SIRI had positive relationship with MoCA scores (p < 0.005). DII also correlated with SIRI in MCI (β = 0.11, p = 0.031). Higher DII and SIRI could definitely increase the risk of MCI, as well as DII and SII (p < 0.005). In conclusion, DII was positively correlated with blood inflammation. The elderly with higher level of DII and SIRI, or DII and SII could be considered as people with higher risk of developing MCI.     

Th17 cell‐derived miR‐155‐5p modulates interleukin‐17 and suppressor of cytokines signaling 1 expression during the progression of systemic sclerosis

Background miR‐155‐5p is associated with autoimmune diseases. T helper 17 (Th17) cells, interleukin (IL)‐17, and suppressor of cytokines signaling 1 (SOCS1) have important roles in the pathogenesis of systemic sclerosis (SSc). The purpose of this study was to explore the role of miR‐155‐5p in the regulation of IL‐17 and SOCS1 expression in Th17 cells and the subsequent effect on SSc disease progression.MethodsTh17 cells were isolated from peripheral blood mononuclear cells of SSc patients and healthy controls (HCs). RT‐qPCR and western blotting were used to examine the expression patterns of miR‐155‐5p, IL‐17, and SOCS1. Luciferase reporter assays were performed to confirm SOCS1 as a target of miR‐155‐5p. RNA pull‐down assays were performed to detect the interaction of IL‐17 and SOCS1 with miR‐155‐5p. In situ hybridization was performed to analyze the co‐expression pattern of miR‐155‐5p and IL17A in Th17 cells.ResultsThe levels of Th17 cell‐derived miR‐155‐5p were significantly up‐regulated in SSc patients compared with HCs, and its levels were negatively correlated with SOCS1 levels. Meanwhile, miR‐155‐5p positively regulated IL‐17 expression levels in Th17 cells isolated from SSc patients as the disease progressed. Using pmirGLO vectors, SOCS1 was confirmed as a target of miR‐155‐5p. The binding status of IL‐17 and SOCS1 to miR‐155‐5p was related to SSc progression. An increase in the co‐localization of miR‐155‐5p and IL‐17 was associated with greater SSc progression.ConclusionsIL‐17 and SOCS1 expression modulated by Th17 cell‐derived miR‐155‐5p are critical for SSc progression, which may provide novel insights into the pathogenesis of SSc.     

女性系统性红斑狼疮患者骨代谢异常的危险因素分析

目的 探讨骨代谢、骨密度与外周血淋巴细胞亚群的关系,初步探索免疫细胞在系统性红斑狼疮(systemic lupus erythematosus, SLE)骨代谢异常中的作用。方法 采用双能X线吸收法(dual energy X-ray absorptiometry, DEXA)检测SLE患者的骨密度,同日检测患者的外周血淋巴细胞亚群分布。结果 共纳入92名SLE女性患者,患者的平均年龄及病程分别为(42.1±14.1)岁、(84.4±73.0)个月。有62.0%(n=57)患者存在骨代谢异常,其中44.6%(n=41)患者为骨量减少,17.4%(n=16)患者并发骨质疏松症,后者还包括9.8%(n=9)发生脆性骨折的患者。全身骨密度最低值与年龄(r=-0.291,P=0.005)、病程(r=-0.239,P=0.022)、绝经状态(r=-0.288,P=0.005)及碱性磷酸酶(r=-0.221,P=0.033)均呈负相关。Logistics分析显示绝经状态(OR=13.0,P<0.001,95%CI 3.43～49.5)、LDL-C(OR=5.74,P=0.002,95%CI ...     

IVIG并传统疗法对难治性神经精神狼疮效果及安全性

目的 探讨静注丙种免疫球蛋白（IVIG）联合传统疗法治疗难治性神经精神狼疮（NPSLE）的效果及安全性。方法 选择难治性NPSLE病人15例,应用糖皮质激素、环磷酰胺及IVIG（400 mg/（kg·d）,连用5 d）治疗。观察IVIG治疗前及治疗后4周神经精神症状、系统性红斑狼疮疾病活动指数（SLEDAI）及脑脊液的变化,同时观察IVIG治疗过程中的不良反应。结果 IVIG治疗后4周,15例NPSLE病人除1例神经源性膀胱及1例精神病病人无效外,其余13例均完全缓解或好转,有效率达86.7%。与治疗前比较,治疗后NPSLE病人脑脊液白细胞计数减少,蛋白含量下降,压力降低,差异均有显著性（t=5.18-7.77,P〈0.05）;SLEDAI降低,差异有显著性（t=14.35,P〈0.05）。治疗过程中无严重不良反应发生。结论 IVIG联合传统方法治疗难治性NPSLE有较好的效果及安全性。     

全身炎症反应与体外循环

体外循环（CPB）可使机体产生大量的炎症介质,引起全身炎症反应综合征（SIRS）,进一步发展导致多器官功能障碍综合征（MODS）,其发病机制目前较为公认的是“二次打击”学说。围体外循环期SIRS的预防和治疗策略很多,CPB装置的改进及减少炎症介质的生成是主要措施。随着对核转录因子NF-kB研究的不断深入,有可能从分子生物学水平调控CPB引发SIRS的程度。     

应用补肾化瘀法组方对化疗骨髓功能保护的临床研究

目的观察中药护髓丸对恶性肿瘤全身化疗患者骨髓功能保护的临床疗效。方法搜集在本院进行全身化疗的恶性肿瘤患者160例,随机分为治疗组和对照组。治疗组90例化疗同时给予护髓丸,对照组70例化疗同时给予三仙丸,对两组化疗结束后7d白细胞（WBC）和血小板（PLT）下降情况等进行评价。结果化疗后7d,治疗组WBC和PLT下降的比例分别为54．4％和31．1％,对照组WBC和PLT下降的比例分别为68．6％和51.4％,两组比较差异有统计学意义（P〈0．05）。结论以补肾化瘀法为理论基础的护髓丸对化疗药物引起的骨髓抑制有确切的预防作用,从而保证了化疗的顺利进行,减轻了患者的经济负担,值得临床进一步研究推广。