解毒化浊促愈汤联合美沙拉嗪肠溶片治疗溃疡性结肠炎的疗效及对炎性细胞因子的影响

目的:研究解毒化浊促愈汤治疗溃疡性结肠炎的疗效及对白细胞介素-6(Interleukin-6,IL-6)、肿瘤坏死因子(Tumor Necrosis Factor-alpha,TNF-α)水平的影响。方法:选取自2017年8月-2018年10月在河南省中医院肛肠科就诊的溃疡性结肠炎患者60例为研究对象,随机将分为观察组与对照组,每组各30例。对照组用美沙拉嗪治疗,观察组在对照组治疗基础上联合解毒化浊促愈汤治疗。两组均连续治疗6周,比较两组患者治疗后的临床疗效以及治疗前后的IL-6、TNF-α水平变化情况。结果:治疗后观察组临床症状明显改善,总有效率为93.3%(28/30),明显高于对照组的70.0%(21/30)。治疗后,两组患者的血清IL-6、TNF-α水平分别较治疗前显著降低(P<0.05),且观察组各指标水平均低于对照组,差异显著(P<0.05)。结论:此方治疗方法能够明显缓解患者的临床症状,抑制炎症反应,提高临床疗效,具有临床推广价值。     

神经内科实习医师血管超声教学的问题及改进方法

血管超声知识是神经内科实习同学的重要学习内容之一,但传统本科教学中对血管超声部分内容局限,使进入神经内科实习的医师血管超声基础知识薄弱,且还存在实践操作的缺乏、教学方式单一等问题,不能在短期内较好的理解及掌握血管超声知识,使得实习效果欠佳。本研究通过对神经内科实习医师血管超声教学中存在的问题进行分析,提出改进方法,可以通过加强实习医师对血管超声的解剖和血流动力学的学习,打牢基础知识,同时将实习医师进行分组,互为模特进行操作实践,在操作实践中加深理论知识的理解和应用。同时还可采用微课等多媒体教学方式,提高实习医师的学习兴趣,显著提高实习效果。     

RG108 调控 TFPI-2 甲基化/TMPRSS4 表达对 NSCLC 细胞增殖和凋亡的影响

目的：探讨RG108对人非小细胞肺癌（non-small cell lung cancer, NSCLC）A549和H1299细胞增殖、凋亡的影响及其可能的作用机制。方法：体外培养A549和H1299细胞，经不同浓度RG108处理后，采用MTT法、流式细胞术分别检测细胞增殖率、细胞周期和凋亡水平；qPCR和Western blotting（WB）法检测细胞内TFPI-2 mRNA和蛋白的表达及TMPRSS4的表达量，以甲基化特异性PCR和比色法检测细胞中TFPI-2启动子区域甲基化的状态和程度；分别采用siRNA-TFPI-2和pcDNA3.0-TMPRSS4质粒敲减TFPI-2或过表达TMPRSS4，然后检测细胞增殖率及凋亡率的变化。结果：RG108处理后，A549和H1299细胞的增殖率显著降低（均P<0.05）、细胞周期阻滞于G1/S期（均P<0.05）而凋亡率显著增加（均P<0.01），细胞中TFPI-2 mRNA及蛋白表达水平均显著升高（P<0.01和P<0.05），同时细胞中TFPI-2启动子区域甲基化程度显著降低（均P<0.05）、TMPRSS4的表达也明显减少（P<0.05）。沉默TFPI-2表达后，A549和H1299细胞的增殖水平显著增加（均P<0.05），而转染pcDNA3.0-TMPRSS4质粒则显著降低细胞的凋亡率（均P<0.05）。结论：RG108能够通过抑制TFPI-2甲基化负向调控TMPRSS4表达进而抑制A549和H1299细胞的增殖，并促进其凋亡。     

Basic fibroblast growth factor promotes doxorubicin resistance in chondrosarcoma cells by affecting XRCC5 expression

Chondrosarcoma is the second most common form of bone cancer and is characterized by its ability to produce an extracellular matrix of the cartilage. High-grade chondrosarcoma is highly aggressive and can metastasize to other parts of the body. Chondrosarcoma is resistant to both conventional chemotherapy and radiotherapy; hence, the current main treatment is still surgical resection. Doxorubicin (Dox) has been shown to significantly improve patient survival compared with untreated chondrosarcoma. However, for patients with metastasis, surgical resection alone can hardly treat them. In addition, drug resistance is one of the leading causes of death in patients with chondrosarcoma. Secreted proteins can mediate cell-cell interactions in the cancer microenvironment, which may be associated with the development of drug resistance. In the present study, chondrosarcoma cells were treated with Dox, the conditioned medium was then collected and changes in secreted proteins were analyzed using the antibody array. Results showed that the Dox-treated group had the highest secretion of basic fibroblast growth factor (bFGF), indicating the effect of bFGF on Dox sensitivity in chondrosarcoma. Furthermore, lentiviral-mediated knockdown and treatment of exogenous recombinant protein were employed to further investigate the effect of bFGF on Dox resistance. Results demonstrated that bFGF can promote the expression of X-ray repair cross-complementing protein 5 (XRCC5), leading to Dox resistance. Secreted bFGF is likely to be detected in serum, in addition to being a biomarker for predicting Dox resistance, the combination of Dox and bFGF/XRCC5 blockers may be a new therapeutic strategy to improve the efficacy of Dox in future.     

子宫内膜癌三维超声血管血流参数与病理学预后指标的相关性

目的探讨子宫内膜癌三维超声血管血流参数与病理学预后指标的相关性。方法选择子宫内膜良性病变患者120例(良性组)与子宫内膜癌患者120例(癌变组),所有患者给予三维超声,记录血管血流参数;采用免疫组化法检测两组病灶病理学预后指标(IGF-1、IGF-2)表达情况并进行相关性分析。结果癌变组的超声病灶形态、内膜回声、增强强度、增强均度与良性组对比差异有统计学意义(P<0.05)。癌变组的IGF-1、IGF-2表达阳性率分别为90.8%、74.2%,显著高于良性组的28.3%、36.7%。癌变组中三维超声血流分级与良性组对比差异有统计学意义(P<0.05)。在癌变组中,直线相关分析显示三维超声血流分级与IGF-1、IGF-2表达阳性率呈显著正相关性(P<0.05)。结论子宫内膜癌患者多表现为IGF-1、IGF-2的高表达,三维超声血管血流分级程度比较高,两者存在相关性,可共同影响子宫内膜癌的发生。     

Rociletinib (CO-1686) enhanced the efficacy of chemotherapeutic agents in ABCG2-overexpressing cancer cells in vitro and in vivo

Overexpression of adenosine triphosphate (ATP)-binding cassette subfamily G member 2 (ABCG2) in cancer cells is known to cause multidrug resistance (MDR), which severely limits the clinical efficacy of chemotherapy. Currently, there is no FDA-approved MDR modulator for clinical use. In this study, rociletinib (CO-1686), a mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), was found to significantly improve the efficacy of ABCG2 substrate chemotherapeutic agents in the transporter-overexpressing cancer cells in vitro and in MDR tumor xenografts in nude mice, without incurring additional toxicity. Mechanistic studies revealed that in ABCG2-overexpressing cancer cells, rociletinib inhibited ABCG2-mediated drug efflux and increased intracellular accumulation of ABCG2 probe substrates. Moreover, rociletinib, inhibited the ATPase activity, and competed with [¹²⁵I] iodoarylazidoprazosin (IAAP) photolabeling of ABCG2. However, ABCG2 expression at mRNA and protein levels was not altered in the ABCG2-overexpressing cells after treatment with rociletinib. In addition, rociletinib did not inhibit EGFR downstream signaling and phosphorylation of protein kinase B (AKT) and extracellular signal-regulated kinase (ERK). Our results collectively showed that rociletinib reversed ABCG2-mediated MDR by inhibiting ABCG2 efflux function, thus increasing the cellular accumulation of the transporter substrate anticancer drugs. The findings advocated the combination use of rociletinib and other chemotherapeutic drugs in cancer patients with ABCG2-overexpressing MDR tumors.     

温阳补肾法对高原类风湿关节炎患者血清25羟维生素D3水平的影响

目的:观察温阳补肾法对高原类风湿关节炎患者血清25羟维生素D3水平的影响。方法:选取2015年7月至2017年8月青海省中医院收治的高原类风湿关节炎患者132例作为研究对象,随机分为对照组和观察组,每组66例。对照组应用常规西医治疗,观察组在对照组治疗基础上应用温阳补肾法治疗,2组均连续治疗3个月。比较2组治疗后临床疗效,统计2组治疗前后主要临床症状与体征、健康状况评定量表(HAQ)评分和DAS28评分,检测2组治疗前后实验室检查指标、血清25羟维生素D3以及血液流变学指标水平。结果:治疗后,观察组临床治疗总有效率显著高于对照组(P 0. 05); 2组关节肿胀指数、关节疼痛指数、关节压痛指数、晨僵时间、关节功能分级和20 m步行时间均较治疗前显著降低(P 0. 05),且观察组均显著低于对照组(P 0. 05); 2组HAQ评分、DAS28评分、类风湿因子(RF)、C反应蛋白(CRP)和红细胞沉降率(ESR)水平均较治疗前显著降低(P 0. 05),且观察组均显著低于对照组(P 0. 05); 2组血清25羟维生素D3水平均较治疗前显著升高(P 0. 05),且观察组显著高于对照组(P 0. 05); 2组红细胞电泳指数、红细胞压积、血浆黏度、全血低切黏度、全血高切黏度水平均较治疗前显著降低(P 0. 05),且观察组均显著低于对照组(P 0. 05)。结论:温阳补肾法治疗高原类风湿关节炎,疗效满意,同时能明显增加血清25羟维生素D3水平。     

PEG-rhG-CSF预防卵巢癌、宫颈癌化疗中性粒细胞缺乏的临床研究

目的:探讨应用聚乙二醇化重组人粒细胞集落刺激因子(PEG-rhG-CSF)对卵巢癌、宫颈癌化疗患者粒细胞减少的影响，并观察不良反应。方法:选择本院2015年4月至2017年6月卵巢癌、宫颈癌患者136例，随机分为对照组（68例）和研究组（68例），对照组应用rhG-CSF，研究组应用PEG-rhG-CSF，两组均化疗两个周期，评估患者两个周期不同时间血常规绝对中性粒细胞计数值（ANC）水平、ANC不同数量发生率和持续时间以及不良反应。结果:研究组患者第一个化疗周期第5 d、第7 d、第10 d和第14 d 及第二个化疗周期第3 d、第5 d、第7 d、第10 d和第14 d血ANC分别为（3.19±0.32）×109/L、（1.93±0.35）×109/L、（2.08±0.39）×109/L、（2.11±0.36）×109/L和（2.79±0.40）×109/L、（2.44±0.33）×109/L、（1.68±0.34）×109/L、（1.71±0.37）×109/L、（1.92±0.34）×109/L，均高于对照组，差异具有统计学意义(P＜0.05)。研究组患者第一个和第二个化疗周期ANC＜1.5×109/L、ANC＜1.0×109/L和ANC＜0.5×109/L发生率分别为23.53%（16/68）、8.82%（6/68）、2.94%（2/68）和29.41%（20/68）、10.29%（7/68）、5.88%（4/68），均低于对照组，差异具有统计学意义(P＜0.05)。研究组患者第一个和第二个化疗周期ANC＜1.5×109/L、ANC＜1.0×109/L和ANC＜0.5×109/L持续时间分别为（3.50±0.18）d、（2.17±0.23)d、（2.06±0.29）d和（4.08±0.22）d、（4.62±0.29）d、（4.11±0.24）d，均短于对照组，差异具有统计学意义(P＜0.05)。研究组中、重度不良反应总发生率为10.29%（7/68），低于对照组23.53%（16/68），差异有统计学意义(P＜0.05)。结论:应用PEG-rhG-CSF能够有效预防卵巢癌、宫颈癌化疗患者粒细胞减少，不良反应显著降低，值得临床推广应用。     

The key role of macrophage depolarization in the treatment of COPD with ergosterol both in vitro and in vivo

Macrophages are the most abundant immune cells in the lung, which play an important role in COPD. The anti-inflammatory and anti-oxidation of ergosterol are well documented. However, the effect of ergosterol on macrophage polarization has not been studied. The objective of this work was to investigate the effect of ergosterol on macrophage polarization in CSE-induced RAW264.7 cells and Sprague-Dawley (SD) rats COPD model. Our results demonstrate that CSE-induced macrophages tend to the M1 polarization via increasing ROS, IL-6 and TNF-α, as well as increasing MMP-9 to destroy the lung construction in both RAW264.7 cells and SD rats. However, treatment of RAW264.7 cells and SD rats with ergosterol inhibited CSE-induced inflammatory by decreasing ROS, IL-6 and TNF-α, and increasing IL-10 and TGF-β, shuffling the dynamic polarization of macrophages from M1 to M2 both in vitro and in vivo. Ergosterol also decreased the expression of M1 marker CD40, while increased that of M2 marker CD163. Moreover, ergosterol improved the lung characters in rats by decreasing MMP-9. Furthermore, ergosterol elevated HDAC3 activation and suppressed P300/CBP and PCAF activation as well as acetyl NF-κB/p65 and IKKβ, demonstrating that HDAC3 deacetylation was involved in the effect of ergosterol on macrophage polarization. These results also provide a proof in immunoregulation of ergosterol for therapeutic effects of cultured C. sinensis on COPD patients.