Magnolol Attenuates Concanavalin A‐induced Hepatic Fibrosis,Inhibits CD4+ T Helper 17 (Th17) Cell Differentiation and Suppresses Hepatic Stellate Cell Activation: Blockade of Smad3/Smad4 Signalling

Magnolol is a pharmacological biphenolic compound extracted from Chinese herb Magnolia officinalis, which displays anti‐inflammatory and antioxidant effects. This study was aimed at exploring the potential effect of magnolol on immune‐related liver fibrosis. Herein, BALB/c mice were injected with concanavalin A (ConA, 8 mg/kg/week) up to 6 weeks to establish hepatic fibrosis, and magnolol (10, 20, 30 mg/kg/day) was given to these mice orally throughout the whole experiment. We found that magnolol preserved liver function and attenuated liver fibrotic injury in vivo. In response to ConA stimulation, the CD4⁺ T cells preferred to polarizing towards CD4⁺ T helper 17 (Th17) cells in liver. Magnolol was observed to inhibit Th17 cell differentiation in ConA‐treated liver in addition to suppressing interleukin (IL)‐17A generation. Hepatic stellate cells were activated in fibrotic liver as demonstrated by increased alpha smooth muscle actin (α‐SMA) and desmin. More transforming growth factor (TGF)‐β1 and activin A were secreted into the serum. Magnolol suppressed this abnormal HSC activation. Furthermore, the phosphorylation of Smad3 in its linker area (Thr179, Ser 204/208/213) was inhibited by magnolol. In vitro, the recombinant IL‐17A plus TGF‐β1 or activin A induced activation of human LX2 HSCs and promoted their collagen production. Smad3/Smad4 signalling pathway was activated in LX2 cells exposed to the fibrotic stimuli, as illustrated by the up‐regulated phospho‐Smad3 and the enhanced interaction between Smad3 and Smad4. These alterations were suppressed by magnolol. Collectively, our study reveals a novel antifibrotic effect of magnolol on Th17 cell‐mediated fibrosis.     

柚皮苷对H_2O_2诱导H9c2心肌细胞损伤保护作用

目的探讨柚皮苷对H_2O_2诱导的H9c2心肌细胞凋亡的保护作用及机制。方法体外培养H9c2心肌细胞,用H_2O_2诱导建立细胞凋亡模型。实验设对照组、模型组、柚皮苷低、中、高剂量组(10、20、40μmol/L),噻唑蓝法检测细胞活力并用显微镜观察各组细胞形态;原位末端标记法检测H9c2心肌细胞凋亡情况;RT-PCR及Western blot法检测凋亡相关因子Bcl-2、Bax、caspase-3 m RNA及蛋白表达。结果与对照组比较,模型组细胞凋亡率[(17.2±2.1)%]明显升高(P<0.01);与模型组比较,10、20、40μmol/L柚皮苷组细胞凋亡率[分别为(10.7±1.9)%、(5.7±1.2)%、(6.4±1.5)%]均下降(均P<0.05)。与对照组比较,模型组H9c2心肌细胞Bcl-2蛋白表达水平(0.76±0.16)明显下调,Bax、caspase-3蛋白表达水平[分别为(5.42±0.52)、(1.09±0.11)]均上调(均P<0.01);与模型组比较,10、20、40μmol/L柚皮苷组H9c2心肌细胞Bcl-2蛋白表达水平[分别为(1.37±0.11)、(1.65±0.09)、(1.65±0.15)]均上调,Bax、caspase-3蛋白表达水平[分别为(2.78±0.55)、(3.43±0.15)、(2.69±0.26)和(0.59±0.08)、(0.77±0.06)、(0.82±0.05)]均下调(均P<0.05)。结论柚皮苷对H_2O_2诱导的H9c2心肌细胞损伤具有一定保护作用,其机制可能与其对凋亡信号途径的抑制作用有关。     

手术护理路径在经尿道等离子前列腺手术配合中的应用

目的 观察经尿道等离子前列腺手术中应用手术护理路径的效果。方法 将接受尿道等离子前列腺手术的45例患者随机分为2组,对照组20例患者接受常规护理,观察组25例患者接受手术护理路径护理,对2组患者的住院时间、护理不良事件发生情况以及健康教育知识掌握情况进行比较分析。结果 对照组患者住院时间为（10.13±1.64）d,观察组为（8.71±1.58）d;护理不良事件发生率对照组为15.0%,观察组为4.0%;健康知识评分对照组为23.48±1.47,观察组为27.86±1.45;2组患者3项指标比较,差异均有统计学意义（P〈0.05）。结论 经尿道等离子前列腺手术中应用手术护理路径较常规护理能缩短住院时间,降低不良事件发生率。     

养正消积胶囊减轻胃癌术后化疗不良反应的临床观察

目的:观察养正消积胶囊对胃癌术后化疗不良反应的疗效。方法:62例胃癌术后患者随机分为两组,治疗组34例给予常规FOLFOX-4(奥沙利铂+5-氟尿嘧啶+亚叶酸钙)化疗方案加用养正消积胶囊,每次4粒,每日3次;对照组28例单纯应用FOLFOX-4化疗方案。化疗结束后观察两组患者外周血象变化、生存质量及不良反应。结果:与对照组比较,治疗组外周血白细胞、血红蛋白与血小板下降幅度更小,差异有统计学意义(P<0.05);且治疗组KPS生存质量评分较高,不良反应较小(均P<0.05)。结论:养正消积胶囊可减少胃癌术后化疗的不良反应,提高患者生存质量。     

乌司他丁联合连续肾脏替代疗法治疗重症急性胰腺炎的临床研究

目的探究乌司他丁联合连续肾脏替代疗法治疗重症急性胰腺炎的临床疗效。方法选取2012年3月—2015年1月牡丹江医学院红旗医院收治的重症胰腺炎患者80例,随机分为对照组和治疗组,每组各40例。对照组在基础治疗之上采用连续肾脏替代疗法。治疗组在对照组基础之上给予乌司他丁注射液20万单位/次,3次/d,加入生理盐水或5%葡萄糖溶液至50 m L持续泵入。两组均连续治疗14 d。观察两组患者的临床疗效,同时比较两组治疗前后C反应蛋白(CPR)、肿瘤坏死因子(TNF-α)、白细胞介素6(IL-6)的变化,比较两组症状体征减轻时间、实验室检查改善时间和ICU住院时间。结果治疗后,两组患者的总有效率分别为65.0%、87.5%,两组比差异有统计学意义(P0.05)。治疗后,两组CPR、TNF-α、IL-6均显著降低,同组治疗前后差异有统计学意义(P0.05);且治疗组的下降程度优于对照组,两组比较差异有统计学意义(P0.05)。治疗组患者的临床症状体征减轻时间、实验室指标改善时间以及ICU住院时间均显著短于对照组,两组比较差异具有统计学意义(P0.05)。结论乌司他丁联合连续肾脏替代疗法治疗重症急性胰腺炎具有较好的临床疗效,可降低全身炎症反应和TNF-α、IL-6水平,具有一定的临床推广应用价值。     

Role of nucleostemin in growth regulation of gastric cancer, liver cancer and other malignancies

AIM: To examine the role of nucleostemin in the growth regulation of gastric cancer, liver cancer and other cancers. METHODS: RT-PCR was used to clone the fragment of nucleostemin cDNA from HEK 293 cells. Eighteen kinds of malignant tumor tissues including gastric adenocarcinoma and liver cancer tissues, 3 kinds of benign tumor tissues, 3 kinds of benign hyperplastic tissues and normal tissues were employed to examine nucleostemin gene expression by RT-PCR, Slot blot, Northern blot and in situ hybridization. RESULTS: We successfully cloned a 570 bp fragment of nucleostemin-cDNA from HEK-293 cells. All detected malignant tumor tissues, benign tumor tissues, and benign hyperplastic tissues had high levels of nucleostemin expression. Nucleostemin was also expressed in human placenta tissue at a high level. In terminally differentiated normal human adult kidney and mammary gland tissues, no nucleostemin expression could be detected. CONCLUSION: Nucleostemin can help regulate the proliferation of both cancer cells and stem cells. It might play an important role in the growth regulation of gastric cancer, liver cancer and other cancers.     

自体骨髓基质干细胞移植联合EPO治疗脊髓损伤的研究

目的：探讨自体骨髓基质干细胞（MSCs）移植联合促红细胞生成素（EPO）对大鼠脊髓损伤（SCI）治疗的效果。方法：培养与纯化骨髓基质干细胞。80只SD大鼠制备脊髓损伤模型,随机分为4组：干细胞移植组、EPO组、联合组和对照组。采用BBB法进行运动能力评分和组织切片观察来评定修复情况。结果：三个实验组与对照组相比,差异具有统计学意义（P〈0.05）,三个实验组均可明显促进大鼠运动功能和损伤后组织结构的恢复,其中联合组效果更显著。结论：骨髓基质干细胞移植联合EPO具有促进大鼠脊髓损伤后神经功能的修复。     

综合疗法对头面部瘢痕的治疗分析

目的:探究综合疗法对头面部瘢痕的治疗效果。方法:选取在我院进行治疗的头面部瘢痕的患者48例,采取手术切除、术中切缘注射糖皮质激素、术后加压、局灶放疗等综合治疗,经过术后随访,观者患者的恢复情况。结果:经过术后的随访,患者术后效果比较好,治愈35例,占72.92%,显效11例,占22.92%,总有效率为95.83%,仅有2例无效,占4.17%,无患者治疗后随访中复发,患者对于治疗比较满意。结论:对于头面部瘢痕的患者来说,采取手术切除、术中切缘注射糖皮质激素、术后加压、局灶放疗等综合治疗,能够取得良好的临床效果,而且患者术后复发率比较低,情况比较满意,值得在临床推广。     

10-乙酰乙酰紫杉醇标准品的制备工艺研究

目的 研究半合成紫杉醇中工艺杂质10-乙酰乙酰紫杉醇的制备方法。方法 选择性地保护紫杉醇的2''位和7位羟基,然后在碱性条件下脱去10位乙酰基,未保护的10位羟基与2,2,6-三甲基-4H-1,3-二噁英-4-酮进行缩合,最后脱去7位和2''位的保护基,制备得到10-乙酰乙酰紫杉醇。结果 以紫杉醇为原料通过5步反应制备得到10-乙酰乙酰紫杉醇,总收率为27%,纯度高达95%。结论 为10-乙酰乙酰紫杉醇标准品的制备提供了简便易行的方法,有利于紫杉醇原料药的质量控制与评价。     

HMGB1 gene silencing inhibits neuroinflammation via down-regulation of NF-κB signaling in primary hippocampal neurons induced by Aβ25–35

High mobility group box 1 protein (HMGB1) is potentially triggered by Aβ oligomers and other sterile injuries, and is a non-histone DNA binding nuclear protein with roles in neural development and neurodegeneration, which contribute to memory impairment and chronic neuroinflammation in the brain. However, the exact molecular mechanisms of HMGB1 activation in Alzheimer's disease (AD) were previously unknown. The present study aimed to elucidate the effects of HMGB1 in Aβ_25–35-induced neuroinflammation in hippocampal neuron cultures. RNA interference (RNAi) HMGB1 treatment significantly reduced Aβ_25–35-induced HMGB1 expression by almost 70% in primary hippocampal neurons. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and enzyme-linked immunosorbent assay (ELISA) demonstrated that short hairpin RNA (shRNA) for HMGB1 ameliorated Aβ_25–35-treated neuroinflammation, including activation of advanced glycosylation end product-specific receptor (RAGE), toll-like receptor 4 (TLR4), and nuclear factor-kappa B (NF-κB)-p65, as well as induced the release of inflammatory mediators such as tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), IL-6, and HMGB1 in primary hippocampal neurons and the culture supernatant. In addition, pretreatment with HMGB1-shRNA dramatically reduced both the degree of nuclear-cytoplasmic HMGB1 translocation of HMGB1 and NF-κB DNA binding. Together, the data indicate that HMGB1 mediates the pathogenesis of AD by activating RAGE/TLR4 signaling and that shRNA targeting HMGB1 may be a promising therapeutic strategy for treating AD.