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??Accumulating evidence strongly supports the involvement of oxidative stress in the etiology of Parkinson's disease (PD). ROS derived from the NOX2-containing NADPH oxidase play important role in the pathogenesis of PD. Our intent was to review the research history about the role of NOX2-containing NADPH oxidase in PD. Neuroprotective effect of heme oxygenase-1 (HO-1) in protecting neurons against PD-related neurotoxin-induced oxidative stress dependant injury, and a major emphasis has been on the relationship between HO-1 and NOX2-containing NADPH oxidase.Specific activation of HO-1 gene expression by pharmacological modulation may represent a novel target for therapeutic treatment of PD through inhibiting NOX/ROS. A new target for PD therapy through inhibiting NOX/ROS, thereby modulating HO-1/NOX2 axis is highlighted.     

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??OBJECTIVE To explore the bacteriostasis and plasmid elimination activities of different extracted parts of traditional Chinese medicine Radix Scutellariae Baicalensis on NDM-1 Acinetobacter calcoaceticus.METHODS The in vitro antibacterial effect of the extracts from Radix Scutellariae Baicalensis was studied. Inhibition zone and minimum inhibitory concentration(MIC) of the alcohol extract and water decoction were examined by using MH agar plates and microdilution susceptibility testing. The growth curve of the NDM-1 Acinetobacter calcoaceticus was tested after being incubated with alcohol extract and water decoction at sub-MIC. At three time points after incubation with different extracts at sub-MIC, photocopy dish method was used to screen plasmid-cured strains of NDM-1 Acinetobacter calcoaceticus. The plasmid-elimination rates and phenotypic changes were compared.RESULTS Both the alcohol extract and water decoction of Radix Scutellariae Baicalensis inhibited the growth of NDM-1 Acinetobacter calcoaceticus. The MICs were 1.56 mg??mL^-1 for the alcohol extract and 6.25 mg??mL^-1 for the water decoction. The growth curve showed that the antibacterial effect of the alcohol extract was more obvious. Both the alcohol extract and water decoction of Radix Scutellariae Baicalensis had some degrees of plasmid elimination effect. The plasmid-elimination rates in the alcohol extract group were higher than those in the water decoction group. The plasmid-elimination rates were 61.27% for the alcohol extract and 49.78% for the water decoction, respectively.CONCLUSION Radix Scutellariae Baicalensis can inhibit the growth of NDM-1 Acinetobacter calcoaceticus and eliminate the drug-resistant plasmid effectively and has the potential to be used to control the spread of pan-drug resistant Acinetobacter strains or be an adjuvant treatment method for clinical infections. Its alcohol extract has better effect.     

脑低灌注患者检测血浆β淀粉样蛋白1-40和1-42水平的价值

目的探讨脑低灌注(CHP)患者血浆中β淀粉样蛋白1-40(Aβ1-40)和Aβ1-42测定的临床价值。方法以ELISA法,检测44例经CT血管成像确定狭窄程度<70%的脑低灌注患者和40例同期对照(HC)者的血浆Aβ1-40和Aβ1-42水平。结果 CHP组血浆Aβ1-40和Aβ1-40/Aβ1-42比值明显高于HC组,而Aβ1-42水平则明显低于HC组。Aβ1-40和Aβ1-42是与血管狭窄相关的独立因素(R2=0.923,P<0.01)。结论脑缺血损伤导致CHP患者血浆Aβ1-40升高和Aβ1-42降低,对其进行检测具有一定的临床诊断价值。     

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??1-Deoxynojirimycin(DNJ), a polyhydroxylated alkaloid,has demonstrated numerous physiological activites, such as anti-diabetes, lipid-lowering,anti-cancer and anti-virus effects.As research continues, related activities have been explained even more clearly, and new physiological activities have been found. In this review, new discoveries of the physiological activities of DNJ and DNJ derivatives were summarized. This will provide pharmaceutical basis for future study and application of DNJ.     

苦参素对免疫性肝纤维化大鼠肝脏组织MMP-1, TIMP-1表达的影响

目的:探讨苦参素对免疫性肝纤维化大鼠基质金属蛋白酶-1(MMP-1)、基质金属蛋白酶-1抑制剂(TIMP-1)表达的影响.方法:建立猪血清诱导的大鼠免疫性肝纤维化模型.SD雄性大鼠44只,随机分为正常对照组、模型组、秋水仙碱组(0.1 mg·kg-1)和苦参素组(60 mg· kg-1),ip,1次/d,连续8周.采用免疫组化方法检测MMP-1,TIMP-1在各组大鼠中的表达.结果:与模型组相比,苦参素组MMP-1表达为(3.42±0.53)％,高于模型组的(2.81±0.53)％,(P＜0.05);苦参索组TIMP-1表达水平为(30.62士3.18)％,明显低于模型组的(41.64±4.51)％,(P＜0.01);苦参素组TIMP-1/MMP-1比值也明显低于模型组(P＜0.01).结论:苦参素能增加免疫性肝纤维化大鼠肝脏组织MMP-1的表达,抑制TIMP-1表达,调节TIMP-1/MMP-1比值,通过对细胞外基质(ECM)的调节起到抗肝纤维化的作用.     

二仙汤及其药物血清对GT1-7细胞增殖及胰岛素样生长因子-1 mRNA的影响

目的 GT1-7细胞株是促性腺激素释放激素(GnRH)神经内分泌细胞株,本实验观察补肾方二仙汤及其温肾、滋阴两个拆方药物血清对 GT1-7细胞株增殖及胰岛素样生长因子-1(IGF-I)mRNA 的影响。方法运用 Northern blot 方法观察 IGF-I mRNA 水平的变化;用 MTT 法观察 GT1-7细胞增殖情况。结果 (1)二仙汤及其温肾、滋阴两个拆方药物血清都能增加 IGF-I mRNA 的表达,其中以滋阴组作用最显著;(2)全方组和滋阴组药物血清能促进 GT1-7细胞增殖,而温肾组无明显变化。结论补肾方二仙汤可能通过作用于 IGF-I 的mRNA 水平而影响 GT1-7细胞的增殖和 GnRH 释放,温肾组和滋阴组作用于该细胞的机制可能有所不同。     

四逆散对溃疡性结肠炎大鼠ICAM-1和VCAM-1的影响

目的: 探讨四逆散对实验性溃疡性结肠炎(UC)大鼠细胞间黏附分子(ICAM)-1和血管内皮细胞黏附分子(VCAM)-1的影响,以及君臣配伍在组方中的作用。方法: SD大鼠50只,分为5组,即正常组、模型组、四逆散组、柴芍枳组和柴芍组;采用免疫法造模,用家兔新鲜结肠黏膜制备抗原乳化液,分别于造模第1,10, 17, 24天注射于大鼠的双侧足跖、腹股沟及背部皮内,造模第2天分组给药,正常组与模型组按照10 mL·kg^-1蒸馏水ig;四逆散组按照1.75 g·kg^-1四逆散溶液ig;柴芍枳组按照1.31 g·kg^-1 ig;柴芍组按照0.88 g·kg^-1 ig;第29天给药后,取材,处死大鼠;采用双抗体夹心ELISA法检测大鼠血清及结肠黏膜组织ICAM-1和VCAM-1水平。结果: 模型组大鼠血清ICAM-1(64.60±4.81)μg·L^-1明显高于正常组(42.35±3.02)μg·L^-1,P<0.05;VCAM-1(0.29±0.01)μg·L^-1显著高于正常组(0.20±0.02)μg·L^-1,P<0.05;模型组大鼠结肠黏膜组织VCAM-1(1.82±0.19)μg·mg^-1显著高于正常组(1.29±0.10)μg·mg^-1,P<0.05;经灌服四逆散后,实验大鼠血清ICAM-1(53.87±2.60)μg·L^-1、VCAM-1(0.22±0.01)μg·L^-1,结肠黏膜组织VCAM-1(1.41±0.08)μg·mg^-1含量均较模型组显著降低,P<0.05。结论: 四逆散能够抑制UC大鼠炎性细胞浸润,减轻炎症反应,其作用机制可能与抑制实验大鼠ICAM-1和VCAM-1的表达有关,方中发挥主要作用的药物可能为柴胡、枳实和芍药。     

川芎嗪对鼠骨关节炎关节软骨MMP-1、TIMP-1表达的影响

目的:观察关节内注射川芎嗪对鼠骨关节炎(Osteoarthritis,OA)模型关节软骨退变及软骨中基质金属蛋白酶-1(MMP-1)、基质金属蛋白酶组织抑制物-1(TIMP-1)表达的影响,探讨川芎嗪对OA的修复作用。方法:50只SD大鼠随机分为空白组、模型组、透明质酸钠组、丹参组和川芎嗪组5组:除空白对照组外,其余四组作左侧跟腱切除建立右膝OA模型。造模后第5周开始,川芎嗪组于右膝关节内注射盐酸川芎嗪注射液作为治疗,于第12周末处死动物,取股骨外髁软骨标本,进行HE染色,光镜下观察其病理改变,以免疫组织化学法检测关节软骨中的MMP-1、TIMP-1水平。结果:川芎嗪组关节软骨退变减缓,Mankin’s评分及软骨中MMP-1的水平非常显著低于模型组(P<0.01),TIMP-1水平较模型组显著上升(P<0.01)。结论:川芎嗪能明显降低OA软骨退变的程度,明显降低OA软骨中MMP-1的水平,增加TIMP-1的水平,具有保护和修复早期OA关节软骨的作用,可延缓OA的病理过程,有可能成为防治OA的良好药物。     

蕨麻正丁醇部位下调缺氧内皮细胞HIF-1α及ET-1表达

[目的]探讨蕨麻正丁醇部位对内皮细胞缺氧损伤的保护机制。[方法]采用人脐静脉内皮细胞(EA.hy926)建立缺氧损伤实验模型,实验设常氧对照组、缺氧模型组、高(3.00 g/L)、中(1.50 g/L)、低浓度(0.75 g/L)蕨麻正丁醇部位组,复方丹参(3.0 g/L)组。胎盘兰染色法测定各组细胞存活率;逆转录-聚合酶链反应(RT-PCR)技术检测各组缺氧诱导因子-1α(HIF-1α)m RNA和内皮素-1(ET-1)m RNA表达,免疫细胞化学染色及Western Blot方法检测HIF-1α蛋白表达。放免法测定培养基中ET-1的活性。[结果]与对照组比较,缺氧模型组细胞存活率显著降低,HIF-1α和ET-1m RNA及蛋白表达增加(P0.01);蕨麻正丁醇部位各剂量组与缺氧模型组比较,细胞存活率显著升高,高、中、低剂量蕨麻正丁醇部位组、复方丹参组细胞HIF-1α和ET-1 m RNA及蛋白水平显著降低(P0.01)。[结论]在缺氧状态下,蕨麻正丁醇部位可能通过HIF-1α途径调控靶基因的表达,从而发挥保护作用。     

常通口服液对肠粘连大鼠血IL-1β、TGF-β1的影响

目的观察常通口服液(大黄、枳实、丹参等)对大鼠肠粘连模型血白细胞介素1β(IL1β)、转化生长因子β1(TGFβ1)的影响。方法选用SD♂大鼠,随机分为6组正常对照组、模型对照组、四磨汤组及常通口服液低、中,高剂量组。除正常对照组外,其余大鼠均按Ellis法制备成肠粘连模型。常通中剂量组与模型对照组于术后第1,3,5,7,9日采血,其余各组于术后第7天取血,酶联免疫吸附法(ELISA)测定IL1β及TGFβ1水平。此外,各组于术后第7天进行粘连程度肉眼分级。结果模型对照组的IL1β、TGFβ1水平明显高于正常对照组(P<0.01);与模型对照组相比,常通口服液中,高剂量组的IL1β,TGFβ1含量均显著降低(P<0.05)。结论常通口服液能降低肠粘连大鼠血清IL1β、TGFβ1含量。细胞因子IL1β、TGFβ在肠粘连形成中发挥一定作用。     

女性患者尿道恶性黑色素瘤5例报告

目的针对我院5例女性尿道恶性黑色素瘤患者,探讨其病例特征、临床诊断及治疗分析。方法对5例女性尿道恶性黑色素瘤患者的临床资料进行分析。结果5例患者确诊为尿道原发性恶性黑色素瘤,经过诊断与治疗后,在随后的4个月至3年,其中2例患者因复发或转移死亡,另3例患者健在。结论女性尿道原发性恶性黑色素瘤少见,易误诊。病理检查应结合病史早期诊治,综合治疗。     

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??OBJECTIVE The aim of this study is to investigate labelings on dermatologic drugs for pregnant women and provide qualitative and quantitative pharmaceutical support for clinical use. METHODS Labelings and formularies on pregnancy of topical drugs were analyzed and sorted according to classification on pregnancy use. Transdermal abilities of the drugs not forbidden nor avoided were evaluated through ACD/LAB 6.0 software and Potts-Guy formulation. Through TOXNET database and dose conversion equation, toxicities on animals were collected and human doses for pregnant women were calculated. RESULTS In dermatologic drugs, there are 16 drugs forbidden, 8 not recommended/avoided/should not be used, 14 used with caution/weighed pros and cons, 7 used under instruction, 16 unclear or with no statement. In topical drugs not forbidden nor avoided, there are 9 drugs?? logKp above-5, butenafine and sertaconazole with strongest transdermal abilities, 7 drugs?? logKp influenced under pH5.5 or pH7.0, with a decline in logK??p compared with logKp, still 15 drugs not influenced by pH, 7 drugs?? toxicities on animals unknown, 14 drugs?? pregnancy human doses under 10 mgkg^-1. CONCLUSION Currently,only a few topical drugs?? instructions on pregnancy are clear. With properties and animal experiments, better pharmaceutical support can be provided for clinical use on qualitative or quantitative reference.     

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??Idiopathic pulmonary fibrosis (IPF) is a typical chronic, progressive fibrosing interstitial pneumonia, which is clinical characterized by progressive worsening of dyspnea and lung function with a poor prognosis. Since the pathogenesis is not clear, there is no efficiency cure for IPF until now. It is discovered that transforming growth factor-?? (TGF-??), a ??master switch?? in the formation and development of IPF, plays an important role in the regulation of alveolar epithelial cells apoptosis, and the promotion of epithelial to mesenchymal transition and extracellular matrix synthesis. In this paper, the latest impacts of TGF-?? on IPF are reviewed, which may provide the clues and evidence for the development of anti pulmonary fibrotic drugs.     

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??OBJECTIVE To develop a LC-MS method for simultaneously quantifying four anti-tuberculosis drugs [isoniazid(INH)??pyrazinamide(PZA)?? ethambutol(EMB) and rifampicin(RIF)] in human cerebrospinal fluid and to help guide the clinical medication. METHODS The drugs in cerebrospinal fluid were extracted by acetonitrile precipitation, and separated on ZORBAX Bonus-RP column(2.1 mm??150 mm,3.5 ??m) with the mobile phase of aqueous solution(containing 0.1% formic acid)-acetonitrile(containing 0.1% formic acid)(80??20) at a flow rate of 0.25 mL??min^-1. Multiple reaction monitoring(MRM) mode was performed combined with electrospray ionization source operating in the positive ionization mode. RESULTS The liner calibration curves of INH??PZA??EMB and RIF were obtained in the concentration range of 20-5 000(r=0.998 6), 120-30 000(r=0.997 7), 20-5 000(r=0.999 4), 60-15 000(r=0.996 2)ng??mL^-1, respectively. The intra-and inter-day precision was less than 15% and the absolute recovery was above 75%. This method was successfully applied to analyze the drugs in cerebrospinal fluid from six clinical samples. CONCLUSION The method is rapid, simple, sensitive and accurate, and proved to be suitable for clinical therapeutic drug monitoring.     

基于靶向调控肿瘤血管的新型纳米递药系统研究进展

高度紊乱的血管系统是恶性实体肿瘤的共性特征,肿瘤血管与肿瘤的发生及发展有着紧密的联系,因而肿瘤血管靶向治疗已成为肿瘤治疗领域的重要组成部分,许多肿瘤血管靶向药物也随之产生。但目前用于肿瘤血管靶向治疗的小分子或抗体药物存在脱靶效应及毒副作用,一定程度上不能满足临床需求。因此,如何改善肿瘤血管靶向药物的有效性和安全性是目前迫切需要解决的问题。纳米疗法为肿瘤血管靶向治疗提供了前所未有的潜力。根据肿瘤血管的特殊结构和功能特点,研究者们设计了多种不同的纳米递送系统用于肿瘤的治疗,如通过纳米技术诱导肿瘤血管栓塞、靶向抑制肿瘤血管生成及提高肿瘤血管灌注等,从而实现肿瘤的安全、有效治疗。笔者综述了近几年靶向调控肿瘤血管的纳米递送系统,为设计安全、有效的新型抗肿瘤药物提供参考。     

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??OBJECTIVE To review and analyze the clinical characteristics of thrombocytopenia induced by vancomycin. METHODS Databases of PUBMED??EMBASE??CBM??CNKI??VIP and WANFANG data (from built to January 2017) were conducted for case reports published in English or Chinese involving thrombocytopenia induced by vancomycin. Literatures were screened, extracted and statistics analysis by two authors independently. RESULTS A total of 2 428 literatures were searched out and 36 were included involving 37 patients. 70.3% of the patients were male, median age was 55.0 years, most of them had underlying diseases and combined with a variety of drugs, 62.2% of which combined with other antimicrobial agents.The clinical manifestation of ADR was thrombocytopenia or complete blood loss associated with or without bleeding symptoms, 45.9% patients were attacted by severe bleeding.The median time of thrombocytopenia for the first and second time was 7.0 d and 24.0 h, the median cumulative dosage was 8.0 g and 3.5 g, the median platelet counts was 23.0??10⁹L^-1 and 77.0??10⁹L^-1, respectively. The median time to platelet nadir counts for the first and second time was 9.0 d and 24.0 h, the median cumulative dosage was 16.0 g and 3.5 g, the median platelet counts was 10.0??10⁹L^-1 and 58.0??10⁹L^-1, respectively. The median time returned to normal platelet counts for the first and second time was 5.0 d and 4.5 d, respectively.For the third time, a single dose of vancomycin was administered and thrombocytopenia developed within 12 h with a nadir platelet counts of 11.0??10⁹L^-1, the platelet counts restored to normal within 7.0 d. Platelet counts returned to normal in 94.6% of patients after vancomycin was discontinued and/or took other measures, three of them died from various reasons but not the ADR of vancomycin. Vancomycin-dependent antibodies were detected in 59.5% of patients. The correlation evaluation of ADR was definite, probable, and possible in 4, 23, and 10 patients, respectively.CONCLUSION High attention should be put on thrombocytopenia induced by vancomycin, male patients with middle or old age, underlying diseases, renal insufficiency and exposure to drugs were the risk factors of thrombocytopenia .Platelet counts should be closely monitored during the use of vancomycin. Testing for drug-dependent antibodies can be helpful for identifying the cause of thrombocytopenia in patients who were receiving vancomycin. More data is need to confirm the incidence and severity of thrombocytopenia induced by vancomycin.     

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??Pancreatic cancer is recognized as one of the highly malignant diseases. Its morbidity is almost equal to the annual mortality. To review the progress of the research on combination therapy of gemcitabine plus nab-paclitaxel in the treatment of pancreatic cancer, the phase ??/?? clinical trials of gemcitabine plus nab-paclitaxel in the treatment of pancreatic cancer in recent years were reviewed and analyzed. Gemcitabine plus nab-paclitaxel has shown exciting effect on metastatic tumor recently. This chemotherapy regimen can improve not only the overall survival but also the progression-free survival of the patients, which brings a ray of dawn for the treatment of pancreatic cancer.     

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??Drug solubility is the key factor that restricts the forming and clinical application of drugs in class II of the biopharmaceutics classification system (BCS). At present, making drugs into solid dispersion is an effective method to improve the dissolution rate. And with the research and development of mesoporous materials, using porous materials as the carrier to prepare solid dispersion becomes a hot research topic in recent years because of their unique structure advantages. Therefore,this paper elaborates the concept and characteristics of porous materials, summarizes the effects of pore size and ordered and surface groups on drug release properties, introduces the preparation method of solid dispersions with porous materials as the carrier, and finally summarizes the classification,characteristics and applications of the common porous materials in order to promote the application of porous materials in the pharmaceutical preparation of poorly water-soluble drugs and improve their bioavailability.     

恶性黑色素瘤临床病理分析与中西医治疗

目的：观察左足拇指恶性黑色素瘤病理形态,进一步探讨其组织起源,病理学诊断及鉴别诊断。方法：对1例恶性黑色素瘤的临床病理学资料进行回顾性分析总结。结果：①患者甲,女,74岁。②左拇指恶性黑色素瘤的病理形态主要表现为上皮样细胞呈巢团样分布,梭行细胞呈束状及不规则排列,分布于真皮层及真皮与表皮连接处,侵及表皮。细胞有明显异型性,侵袭性。③恶性黑色素瘤与良性痣、其他恶性肿瘤的鉴别,免疫组化有助于诊断。结论：①恶性黑色素瘤起源于外胚层。②恶性黑色素瘤容易发生误诊,免疫组化检查有助于鉴别诊断。⑧恶性黑色素瘤恶性程度较高,易转移,治疗上宜旱发现,早治疗,综合治疗。