Tumor-stroma ratio is an independent predictor for survival in NSCLC

Tumor-stroma ratio (TSR) has been identified as a new and practicable prognostic factor in some solid tumors. The aim of the study is to evaluate the prognostic value of TSR in non-small cell lung cancer (NSCLC). A total of 404 patients who underwent surgery resection for NSCLC were included in this study. TSR was assessed visually on the hematoxylin-stained tissue sections of surgical specimens. Patients with more than 50% intratumor stroma were quantified as the stroma-rich group and those with less than 50% as the stroma-poor group. In 404 cases of tissue samples, 302 cases were included in the stroma-poor group, while 102 cases in stroma-rich group. The different expression of TSR in NSCLC tissue was not correlated with gender, age, smoking history, tumor diameter, histology, differentiation grade and pTNM staging. In the Cox univariate and multivariate analyses of the 5-year OS, the HRs of the TSR were 1.818 (95% CI; 1.323-2.497; P<0.001) and 1.748 (95% CI; 1.262-2.422; P<0.05), respectively. As for DFS, the HRs were 1.715 (95% CI; 1.249-2.354; P<0.001) and 1.570 (95% CI; 1.135-2.172; P<0.05). Stroma-rich tumors were associated with poor prognosis and an increased risk of relapse, which may serve as a new prognostic histological characteristic in NSCLC.     

Assessment of the Safety and Efficacy of an Attenuated Live Vaccine Based on Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus

The safety and efficacy of the JXA1-R vaccine, an attenuated strain of highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV), were examined using an intramuscular challenge model in piglets. The JXA1-R vaccine was obtained by passing HP-PRRSV JXA1 through Marc-145 cells (82nd passage). Genomic sequence comparisons showed that strain JXA1-R and its parental strain, JXA1, differ by 47 amino acids, and most of these differences are scattered throughout the PRRSV genome. Four-week-old PRRSV-free piglets were inoculated intramuscularly with JXA1-R vaccine (10^3.0, 10^4.0, 10^5.0, 10^6.0, and 10^7.0 50% tissue culture infective doses [TCID₅₀]/ml for groups 1 to 5, respectively) and then challenged intramuscularly with the 5th passage virus of JXA1 virus (JXA1-F5, 3 ml × 10^4.5 TCID₅₀/ml) 28 days after inoculation. The humoral immune response, swine growth, clinical signs, and differential organ lesions were monitored. The results showed that all vaccinated piglets had a perceptible humoral immune response to vaccination after day 7, which then promptly increased, almost reaching the maximum sample/positive (S/P) ratio value at 28 days postimmunization. Viremia detection indicated that the viral replication levels of the challenge virus in the immunized groups (immunization doses ≥10^4.0/ml) were significantly lower than that of the virus-challenged unvaccinated control group. Piglets in groups 2 to 5 were effectively protected against lethal HP-PRRSV infection and did not show any obvious changes in body temperature or clinical signs of disease at any point during the experiment. However, two of five piglets in group 1 showed mild pathological lesions and transitory high fever. These results suggest that JXA1-R (TCID₅₀/ml ≥10^4.0) is sufficiently attenuated and can provide effective protection against the lethal wild-type HP-PRRSV.     

Thyroid-Stimulating Hormone Levels within the Reference Range Are Associated with Serum Lipid Profiles Independent of Thyroid Hormones

Context and Objective: Dyslipidemia in thyroid dysfunction has always been attributed to changes in thyroid hormone (TH) levels. We hypothesized that TSH plays an important role in lipid metabolism independent of TH. Design and Setting: We conducted a cross-sectional study to investigate the relationship between serum TSH levels and lipid profiles after controlling for free T(3), free T(4), total T(3), total T(4) and nonthyroid factors relevant to lipid metabolism in euthyroid Chinese subjects. Main Outcome Measures: General linear analysis was performed to determine whether the impact of TSH on serum lipid levels is independent of the TH levels. Moreover, path analysis, an evolutionary multivariable regression technique, was conducted to test whether there is a direct and/or indirect effect between serum TSH and total cholesterol (TC) levels. Additionally, the odds ratios (95% confidence interval) for hypercholesterolemia in relation to TSH categories were calculated. Results: A total of 3664 euthyroid subjects were finally analyzed. There was a significant linear trend toward higher log TC (P = 0.021) and log triglyceride (P = 0.001) levels with increasing serum TSH levels within the reference range, which remained significant after adjusting for factors such as TH levels, age, and smoking. Most importantly, the total effect of TSH on TC levels (total effect(TC, TSH) = 0.05253) includes a direct effect (direct effect(TC, TSH) = 0.05979) and an indirect effect via TH. Compared with subjects in the lower part of the reference range (TSH level, 0.27-0.61 mIU/liter), the adjusted odds ratio for hypercholesterolemia was 3.239 (95% confidence interval, 1.392-7.538; P = 0.007) for those in the upper category (TSH level, 4.61-5.5 mIU/liter). Conclusions: The variation in normal TSH levels is partially related to the lipid components and hypercholesterolemia in euthyroid subjects and includes both TH-dependent and TH-independent effects. Our study suggests the importance of controlling TSH in hypothyroid subjects.     

The mechanism of astragaloside IV promoting sciatic nerve regeneration

3-O-beta-D-xylopyranosyl-6-O-beta-D-glucopyranosyl-cycloastragenol (astragaloside Ⅳ), the main active component of the traditional Chinese medicine astragalus membranaceus, has been shown to be neuroprotective. This study investigated whether astragaloside Ⅳ could promote the repair of injured sciatic nerve. Denervated sciatic nerve of mice was subjected to anastomosis. The mice were intraperitoneally injected with 10, 5, 2.5 mg/kg astragaloside Ⅳ per day for 8 consecutive days. Western blot assay and real-time PCR results demonstrated that growth-associated protein-43 expression was upregulated in mouse spinal cord segments L4-6 after intervention with 10, 5, 2.5 mg/kg astragaloside Ⅳ per day in a dose-dependent manner. Luxol fast blue staining and electrophysiological detection suggested that astragaloside Ⅳ elevated the number and diameter of myelinated nerve fibers, and simultaneously increased motor nerve conduction velocity and action potential amplitude in the sciatic nerve of mice. These results indicated that astragaloside Ⅳ contributed to sciatic nerve regeneration and functional recovery in mice. The mechanism underlying this effect may be associated with the upregulation of growth-associated protein-43 expression.     

Pyridoxamine ameliorates methylglyoxal-induced macrophage dysfunction to facilitate tissue repair in diabetic wounds

Methylglyoxal (MGO) is a highly reactive dicarbonyl compound formed during hyperglycaemia. MGO combines with proteins to form advanced glycation end products (AGEs), leading to cellular dysfunction and organ damage. In type 2 diabetes mellitus (T2DM), the higher the plasma MGO concentration, the higher the lower extremity amputation rate. Here, we aimed to identify the mechanisms of MGO-induced dysfunction. We observed that the accumulation of MGO-derived AGEs in human diabetic wounds increased, whereas the expression of glyoxalase 1 (GLO1), a key metabolic enzyme of MGO, decreased. We show for the first time that topical application of pyridoxamine (PM), a natural vitamin B6 analogue, reduced the accumulation of MGO-derived AGEs in the wound tissue of type-2 diabetic mice, promoted the influx of macrophages in the early stage of tissue repair, improved the dysfunctional inflammatory response, and accelerated wound healing. In vitro, MGO damaged the phagocytic functions of M1-like macrophages induced by lipopolysaccharide (LPS), but not those of M0-like macrophages induced by PMA or of M2-like macrophages induced by interleukins 4 (IL-4) and 13 (IL-13); the impaired phagocytosis of M1-like macrophages was rescued by PM administration. These findings suggest that the increase in MGO metabolism in vivo might contribute to macrophage dysfunction, thereby affecting wound healing. Our results indicate that PM may be a novel therapeutic approach for treating diabetic wounds. MGO forms protein adducts that cause macrophage dysfunction. These adducts cause cell and organ dysfunction that is common in diabetes. Pyridoxamine scavenges MGO to ameliorate this dysfunction, promoting wound healing. Pyridoxamine could be used therapeutically to treat non-healing diabetic wounds.     

芎柰抗骨关节炎有效部位研究

目的 研究川芎山柰抗关节炎作用的有效部位.方法 利用小鼠热板法、乙酸扭体法和二甲苯致小鼠耳廓肿胀模型,比较芎柰水提物、醇提物的抗炎镇痛作用;采用木瓜蛋白酶诱导大鼠骨关节炎模型,比较不同溶剂萃取物的抗炎作用.结果 在相同剂量下,芎柰醇提物镇痛作用较水提物强(P＜0.05);芎柰醇提物乙酸乙酯萃取物能有效减轻骨关节炎大鼠踝关节宽度和足趾肿胀(P＜0.01),显著降低血清IL-1β和NO水平(P＜0.01),改善其病理学改变.结论 芎柰醇提物具有明显的抗炎镇痛作用,其乙酸乙酯部位是芎柰抗关节炎的最有效部位.     

The anti-tumor effect of pachymic acid on osteosarcoma cells by inducing PTEN and Caspase 3/7-dependent apoptosis

Pachymic acid (PA) is a lanostane type triterpenoid isolated from Poria cocos, which possesses an anti-tumor effect in breast cancer, prostate cancer, lung cancer, and bladder cancer cells. In this study, we investigated the effect of PA on the growth and apoptosis of human immortalized cell line (HOS) and primary osteosarcoma cells by a Cell Counting Kit-8 (CCK-8) and Annexin V and propidium iodide (PI) staining, respectively. Western blot was used to measure the expression of cleaved Caspase 3, PTEN, and AKT, as well as the AKT phosphorylation. The Caspase 3 activity was determined using the Caspase-3 Colorimetric Assay Kit. From the results, PA significantly reduced cell proliferation in a concentration- and time-dependent manner. PA also induced cell apoptosis in a dose-dependent fashion. PA treatment led to increased Caspase 3 activation and PTEN expression, as well as reduced AKT phosphorylation. Moreover, Ac-DEVD-CHO (a Caspase 3/7 inhibitor) pre-treatment or PTEN knockdown partially blocked the effects of PA on cell proliferation and apoptosis. Caspase 3/7 inhibitor had an additive effect with PTEN knockdown. Collectively, our results suggested that induction of apoptosis by PA was mediated in part by PTEN/AKT signaling and Caspase 3/7 activity. This study provides evidence that PA might be useful in the treatment of human osteosarcoma.     

频谱多普勒评价兔早期动脉粥样硬化的局限性

目的 :观察动脉硬化模型兔腹主动脉血流频谱 ,探讨超声多普勒检查诊断早期动脉硬化的局限性。方法 :新西兰大白兔 3 0只 ,随机分为正常饲料组 (control group,CG) 12只 ,高脂饲料组 (observation group,OG) 18只 ;分别于第 0周、 4周、 8周、 10周、 12周超声检查腹主动脉收缩期峰值血流速度 (systolic velocity,SV)、舒张末期血流速度 (diastolic velocity,DV)、平均血流速度 (mean velocity,MV)、搏动指数 (pulsitile index,PI)、阻力指数 (resistent index,RI)、 SV/ DV,分析所有实验数据并进行统计学处理 ,比较 CG和 OG之间的差异。结果 :从第 4周起 ,OG出现高脂血症 ,第 8周以后 ,动脉粥样硬化模型建立。与第 0周获得的数据比较 ,OG除 SV、 MV、 SV/ DV的改变具有统计学差异 (P<0 .0 5)外 ,余改变均不明显 (P>0 .0 5) ;在第 4～ 10周以后 ,OG上述测量指标即显示了和动脉硬化血流动力学一致的改变 ;第 4～ 12周、 8～ 12周和 10～ 12周所获得平均 PI,CG和 OG比较有显著性差异 (P<0 .0 5) ,但两组在匹配的时间段内的 PI均未显示有统计学意义的差异 (P>0 .0 5)。结论 :单纯以频谱多普勒观察血流速度及其血流指数的改变尚不能对实验动物兔动脉硬化做出早期诊断     

一种简易可行的血液流变学参数处理方法

本文通过理论分析及冠心病患者的流变学数据观察说明只要测得全血在观粘度、血浆粘度及血细胞压积，即可通过简单的计算得到较全面、较理想地反映血液流变特性变化的指标。