消退素D2对椎间盘突出所致根性神经痛的作用

目的 观察消退素D2（RvD2）对非压迫性腰椎间盘突出症所致根性神经痛模型大鼠的影响。 方法 选取雄性Sprague-Dawley(SD)大鼠36只,按随机数字表法分为假手术组,模型组和RvD2组,每组大鼠12只。模型组和RvD2组均采用自体髓核组织填充法制作非压迫性腰椎间盘突出症模型,假手术组仅暴露相应手术部位,不作其它处理。造模成功后连续3d对假手术组和模型组均鞘内给予磷酸盐缓冲液（PBS）10μl,RvD2组则鞘内给予RvD2溶液10ng/10μl。于造模前1d和造模成功后连续7d观察3组大鼠术侧的50%缩足阈值（PWT）,并于造模成功后第7天获取大鼠术侧L4至L6节段脊髓背角,采用蛋白质印迹法测定磷酸化的蛋白激酶B(p-AKT),蛋白激酶B(t-AKT),磷酸化的糖原合成激酶3β(p-GSK-3β)和糖原合成激酶3β(GSK-3β)的蛋白表达量,并用酶联免疫吸附试验测定肿瘤坏死因子α（TNF-α）、白介素-6（IL-6）、转化生长因子-β1（TGF-β1）和白介素-10（IL-10）的蛋白表达含量。 结果 造模成功后第1～7天,模型组和RvD2组大鼠50%PWT与假手术组同时间点比较,差异均有统计学意义（P<0.05）;造模成功后第3～7天,RvD2组的50%PWT分别为（6.31±2.11）g、（7.37±1.58）g、（7.96±1.73）g、（8.46±1.55）g、(8.55±1.44)g,与模型组同时间点比较,差异均有统计学意义（P<0.05）。造模成功后第7天,模型组和RvD2组的p-AKT和p-GSK-3β蛋白阳性表达水平与假手术组比较,差异有统计学意义（P<0.05）;且RvD2组的p-AKT和p-GSK-3β蛋白阳性表达水平与模型组比较,差异亦有统计学意义(P<0.05)。造模成功后第7天,模型组和RvD2组大鼠脊髓背角促炎细胞因子TNF-α和IL-6以及抗炎因子TGF-β1和IL-10的蛋白表达水平与假手术组比较,差异均有统计学意义（P<0.05）; 且RvD2组促炎细胞因子TNF-α和IL-6以及抗炎因子TGF-β1和IL-10的蛋白表达水平与模型组比较,差异均有统计学意义（P<0.05）。 结论 RvD2可减轻非压迫性椎间盘突出大鼠的根性神经痛,其机制可能与抑制GSK-3β活性,下调促炎因子以及上调抗炎因子的蛋白表达水平相关。     

After neoadjuvant chemotherapy platelet/lymphocyte ratios negatively correlate with prognosis in gastric cancer patients

Introduction

Circulating predictors prognostic factors of neoadjuvant chemotherapy, which identify the patients who are potential possibly to benefit from it are limited at present. In this research, we aimed to compare the prognostic significance of neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) in patients with locally advance gastric carcinoma who were treated with neoadjuvant chemotherapy (NAC) followed by D2 gastrectomy.

Materials and methods

From 2007 to 2015, 91 patients with locally advanced gastric cancer treated with NAC followed by D2 gastrectomy included in this retrospective cohort study. The correlation of clinical data, including tumor regression, response evaluation, tumor location, pathological type, systemic therapy, tumor size (cm), neural invasion, lymphatic‐vascular invasion, ypTNM stage, and survival prognosis were analyzed.

Results

Platelet/lymphocyte ratio and neutrophil/lymphocyte ratio in gastric cancer patients were higher than in matched normal volunteers. PLR levels higher after neoadjuvant chemotherapy are associated with worse OS. Multivariate Cox proportional analysis showed that pre‐neoadjuvant chemotherapy PLR was an independent prognostic factor.

Conclusions

Pre‐neoadjuvant chemotherapy PLR may be a feasible biomarker for survival prognosis in patients with locally advanced gastric cancer. PLR and NLR were reduced after neoadjuvant chemotherapy. After neoadjuvant chemotherapy, PLR level was negatively correlated with survival prognosis.

     

Trends in Medicare Part D Medication Therapy Management Eligibility Criteria

Background

To increase the enrollment rate of medication therapy management (MTM) programs in Medicare Part D plans, the US Centers for Medicare & Medicaid Services (CMS) lowered the allowable eligibility thresholds based on the number of chronic diseases and Part D drugs for Medicare Part D plans for 2010 and after. However, an increase in MTM enrollment rates has not been realized.

Objectives

To describe trends in MTM eligibility thresholds used by Medicare Part D plans and to identify patterns that may hinder enrollment in MTM programs.

Methods

This study analyzed data extracted from the Medicare Part D MTM Programs Fact Sheets (2008–2014). The annual percentages of utilizing each threshold value of the number of chronic diseases and Part D drugs, as well as other aspects of MTM enrollment practices, were analyzed among Medicare MTM programs that were established by Medicare Part D plans.

Results

For 2010 and after, increased proportions of Medicare Part D plans set their eligibility thresholds at the maximum numbers allowable. For example, in 2008, 48.7% of Medicare Part D plans (N = 347:712) opened MTM enrollment to Medicare beneficiaries with only 2 chronic disease states (specific diseases varied between plans), whereas the other half restricted enrollment to patients with a minimum of 3 to 5 chronic disease states. After 2010, only approximately 20% of plans opened their MTM enrollment to patients with 2 chronic disease states, with the remaining 80% restricting enrollment to patients with 3 or more chronic diseases.

Conclusion

The policy change by CMS for 2010 and after is associated with increased proportions of plans setting their MTM eligibility thresholds at the maximum numbers allowable. Changes to the eligibility thresholds by Medicare Part D plans might have acted as a barrier for increased MTM enrollment. Thus, CMS may need to identify alternative strategies to increase MTM enrollment in Medicare plans.     

Immune Modulation by Vitamin D and Its Relevance to Food Allergy

Apart from its classical function in bone and calcium metabolism, vitamin D is also involved in immune regulation and has been linked to various cancers, immune disorders and allergic diseases. Within the innate and adaptive immune systems, the vitamin D receptor and enzymes in monocytes, dendritic cells, epithelial cells, T lymphocytes and B lymphocytes mediate the immune modulatory actions of vitamin D. Vitamin D insufficiency/deficiency early in life has been identified as one of the risk factors for food allergy. Several studies have observed an association between increasing latitude and food allergy prevalence, plausibly linked to lower ultraviolet radiation (UVR) exposure and vitamin D synthesis in the skin. Along with mounting epidemiological evidence of a link between vitamin D status and food allergy, mice and human studies have shed light on the modulatory properties of vitamin D on the innate and adaptive immune systems. This review will summarize the literature on the metabolism and immune modulatory properties of vitamin D, with particular reference to food allergy.     

A Randomized,Double-Blind,Parallel Study to Evaluate the Dose-Response of Three Different Vitamin D Treatment Schemes on the 25-Hydroxyvitamin D Serum Concentration in Patients with Vitamin D Deficiency

Many people worldwide are vitamin D (VTD) deficient or insufficient, and there is still no consensus on the dose of VTD that should be administered to achieve a 25(OH)D concentration of 20 or 30 ng/mL. In this study, we aimed to determine an adapted supplementation of VTD able to quickly and safely increase the vitamin D status of healthy adults with low 25(OH)D. One hundred and fifty (150) subjects were randomized into three groups, each to receive, orally, a loading dose of 50,000, 100,000 or 200,000 IU of VTD3 at Week 0, followed by 25,000, 50,000 or 100,000 IU at Week 4 and Week 8. Whereas 25(OH)D baseline values were not different between groups (p = 0.42), a significant increase was observed at Week 12 (p < 0.0001) with a mean change from baseline of 7.72 ± 5.08, 13.3 ± 5.88 and 20.12 ± 7.79 ng/mL. A plateau was reached after eight weeks. No related adverse event was recorded. This study demonstrated a linear dose-response relationship with an increase in 25(OH)D levels proportional to the dose administered. In conclusion, a loading dose of 200,000 IU VTD3 followed by a monthly dose of 100,000 IU is the best dosing schedule to quickly and safely correct the VTD status.     

Flow cytometry evaluation of in vitro cellular necrosis and apoptosis induced by silver nanoparticles

Particles possess unique properties in the nanoscale, e.g., enhanced catalytic activity, high surface area, and light emission/absorption properties, that might result in interference with colorimetric in vitro cytotoxicity assays such as MTT, XTT or MTS. Alternatively, assays that do not use spectrophotometric detection, such as trypan blue exclusion or flow cytometry (FC) based assays, are less likely to be influenced by nanoparticle interference. The aim of this study was to evaluate FC assays to assess the cytotoxicity of three different sizes (10, 100, or 200 nm) of silver nanoparticles (AgNPs) at different mass concentrations (1, 25, or 50 ug/ml) in L-929 fibroblast cells. After 4 h and 24 h exposure, cell necrosis and apoptosis were assessed using 7-AAD and Annexin V dyes, respectively, with FC. The data indicate that cell necrosis and apoptosis in AgNP-exposed fibroblasts depends on dose, exposure time, and AgNP size. The data indicate that AgNPs produced a dose- and time-dependent decrease in cell viability; however, 10 nm AgNPs were significantly more toxic than larger-sized particles. Thus, standard FC assays can be utilized to assess apoptosis and necrosis in response to nanomaterial exposure.