Potentiating activity of luteolin on membrane permeabilizing agent and ATPase inhibitor against methicillin-resistant Staphylococcus aureus

Objective:To investigate the mechanism of antibacterial activity of luteoiin(LUT) against methicillin-resistant Staphylococcus aureus(MRSA).Methods:The mechanism of anti-MRSA activity of LUT was analyzed by the viability assay in membrane permeabilizing agent ATPase inhibitors,and peptidoglycan(PGN) derived from Staphylococcus aureus(S.aureus).Also,transmission electron microscopy was used to monitor survival characteristics and changes in S.aureus morphology.Results:Compared to the LUT alone,the optical density of suspensions treated with the combination of 125 μg/mL Tris and 230 μg/mL DCCD were reduced to 60%and 46%,respectively.PGN(15.6 μg/mL) gradually impeded the activity of LUT,and PGN(62.5 μg/mL) completely blocked the activity of LUT on S.aureus.Conclusions:Increased susceptibility to LUT with me Tris and DCCD combinations is evident in all tested MRSA isolates.The results indicate LUT synergy in increasing cytoplasmic membrane permeability and inhibiting ATPase.S.aureus PGN directly blocks the antibacterial activity of LUT,suggesting the direct binding of LUT with PGN.These findings may be validated for the development of antibacterial agent for low MRSA resistance.

Determination of Fragmentation Schemes and Metabolites of Fluorinated Histone Deacetylase Inhibitors for Use as Positron Emission Tomography Imaging Agents Using HPLC-MS/MS

High performance liquid chromatography coupled with tandem mass spectrometry was developed and validated as a method for the analysis of fluorinated histone deacetylase inhibitors (F-HDACi), and then employed to study their metabolism in biosystems. Four HDACi analogs labeled with the positron emission nuclide 18F constitute a group of potential positron emission tomography imaging agents, which were developed by the Institute of Nuclear Energy Research (INER) and coded as INER-1577 #1, #2, #3, and #4 during animal studies for the diagnosis of dementia. The performance of the method was found to be suitable for the determination of analog #3, and it was employed to determine the structures and fragmentation mechanisms of all four analogs and to study the biotransformations of analogs #3 and #4. The results indicated that the method used for the determination of analog #3 was suitable for determining the abundance of the analogs in chemical and biochemical tests with high precision, accuracy, reproducibility, and recovery. Weaknesses in the chemical bonding of the analogs were found to involve the fluoro, dimethylamino, and benzamide groups in a fragmentation mechanism deduced via tandem mass spectrometry. The metabolites of analogs #3 and #4 in rat liver microsomes and rat plasma were also identified to clarify their characteristic behaviors in biosystems. The major product of analogs #3 in liver microsomes was produced by hydroxylation of the benzylic carbon atom, but in rat plasma the metabolites of analog #3 were produced by hydrolysis of the benzamide group to give a diaminobiphenyl compound with the simultaneous replacement of a fluorine atom by a hydroxyl group. The metabolites of analog #4 in liver microsomes were produced by hydroxylation of the benzylic carbon atom and hydrolysis of the benzamide bond. The results of the studies characterized the chemical and biochemical behaviors of the series F-HADCi analogs.

A Study on Inhibitors for the Prevention of Hydrate Formation in Gas Transmission Pipeline

Gas Hydrate is usually formed during the transportation and treatment of oil and gas, resulting in the plugging of gas pipeline and equipment. Three thermodynamic calculation formulas are analyzed to deal with this problem. The lowering of the freezing point of the inhibitors △T is used to calculate the formation temperature of natural gas hydrates. This is considered to be a good approach because it is not limited by what kind and what concentration of inhibitors one uses. Besides, the rate of lowering of the freezing point could be easily measured. The result of testing methanol and mono-ethylene glycol in a reactor shows that adding 10% inhibitors to the reactor can prevent the hydrates formation. Kinetic inhibitors are favored in the present research. They are divided into two types, polymer and surface-active agents. Their characteristics, mechanisms, and application prospect are separately discussed. Polymer inhibitors exhibit better efficiency. The result of field application of VC-713 inhibiter is also given in this article. In practice, the combination of thermodynamic inhibitors and kinetic inhibitors gives better result.

Novel therapeutic agents in the treatment of metastatic colorectal cancer

Over the past couple of decades considerable progress has been made in the management of metastatic colorectal cancers(mCRC) leading to a significant improvement in five-year survival. Although part of this success has been rightly attributed to aggressive surgical management and advances in other adjunct treatments, our understanding of the pathogenesis of cancer and emergence of newer molecular targets for colon cancer has created a powerful impact. In this review article we will discuss various targeted therapies in the management of mCRC. Newer agents on the horizon soon to be incorporated in clinical practice will be briefly reviewed as well.

Are proton pump inhibitors a new antidiabetic drug? A cross sectional study

AIM: To investigate the effect of proton pump inhibitors (PPIs) on glycemic control (HbA1c) in type 2 diabetic patients. METHODS: A crosssectional study of consecutive in-patients admitted to hospital in any department during the fi rst semester of the year 2010 who had a recent HbA1c measurement. The study excluded those with a diagnosis of hyperglycemic decompensation, diabetic onset or pregnancy. It compared HbA1c levels of those taking PPIs and those not. RESULTS: A total of 97 patients were recruited. The average HbA1C level was 7.0% ± 1.2%. Overall PPI consumption was 55.7%. HbA1c was signif icantly lower in individuals who took PPIs: -0.6%, 95% CI: -0.12 to-0.83. People who used PPIs with some type of insulin therapy had a HbA1c reduction by -0.8%, 95% CI: -0.12 to -1.48. For the rest of subgroup analysis based on the antidiabetic drug used, PPI consumption always exhibited lower HbA1c levels. CONCLUSION: PPIs seems to be consistently associated with better glycemic control in type 2 diabetes. HbA1c reduction observed is similar to incretin-based therapies.

Actinolactomycin,a New 2-Oxonanonoidal Antitumor Antibiotic Produced by Streptomyces flavoretus 18522,and its Inhibitory Effect on the Proliferation of Human Cancer Cells

Actinolactomycin 1, a new 2-oxonanonoidal antitumor antibiotic, was isolated from the fermentation broth of Streptomyces flavoretus 18522 through a bioassay-guided separation procedure. The structure of 1 was determined as 4,7-dihydroxy-3,9-dimethyl-2-oxonanone by the spectroscopic methods. Compound 1 inhibited the proliferation of A2780, K562, HCT-15, A549 and HeLa cells with the IC50 values of 1.4 ± 0.4 μmol/L, 8.4 ± 4.7 μmol/L, 9.4 ± 2.2 μmol/L, 15.4 ± 5.6 μmol/L and 13.7 ± 2.0 μmol/L, respectively. Flow cytometric analysis indicated that 1 could inhibit the cell cycle of tsFT210, A2780 and K562 cells mainly at the G0/G1 phase and could also induce apoptosis in K562 cells.

Pharmacokinetic and Pharmacodynamic Properties of Batifiban Coadministered with Antithrombin Agents in Chinese Healthy Volunteers

The combined use of batifiban, a synthetic platelet GP II b/IIIa receptor antagonist, and an- tithrombin agents is an attractive option for the treatment of patients with non-ST-segment elevation （NSTE） acute coronary syndrome （ACS） and those scheduled for percutaneous coronary intervention. To observe whether antithrombin agents affect the pharmacokinetic and pharmacodynamic properties of batifiban in combination therapy and optimize clinical administration dosage of batifiban, an open-label and parallel study was conducted. Thirty healthy subjects were randomly divided into three groups, which were sequentially treated with batifiban alone, or oral coadministration of clopidogrel, aspirin and UFH, or batifiban coadministered with these antithrombin agents. Blood samples were collected at pre-specified time points. The evaluation index included the inhibition of platelet aggregation and pharmacokinetic parameters. The pharmacokinetic parameters of batifiban and batifiban coadministered with antithrombin agents showed no significant differences. The mean inhibition rate of platelet aggre- gation （%） suggested that neither batifiban alone nor antithrombin agents alone could provide such po- tent inhibition rate （〉80%） to obtain the best clinical efficacy, but they had a synergistic effect on plate- let inhibition. No serious adverse effects were observed. The results in these healthy subjects suggest that batifiban coadministrated with antithrombin agents could achieve optimum clinical treatment effect for patients with NSTE ACS, and also those scheduled for percutaneous coronary intervention.

Hepatitis C virus protease inhibitor-resistance mutations: Our experience and review

Direct-acting antiviral agents(DAAs)for hepatitis C virus(HCV)infection are one of the major advances in its medical treatment.The HCV protease inhibitors boceprevir and telaprevir were the first approved DAAs in the United States,Europe,and Japan.When combined with peginterferon plus ribavirin,these agents increase sustained virologic response rates to70%-80%in treatment-na?ve patients and previoustreatment relapsers with chronic HCV genotype 1 infection.Without peginterferon plus ribavirin,DAA monotherapies increased DAA-resistance mutations.Several new DAAs for HCV are now in clinical development and are likely to be approved in the near future.However,it has been reported that the use of these drugs also led to the emergence of DAA-resistance mutations in certain cases.Furthermore,these mutations exhibit cross-resistance to multiple drugs.The prevalence of DAA-resistance mutations in HCV-infected patients who were not treated with DAAs is unknown,and it is as yet uncertain whether such variants are sensitive to DAAs.We performed a population sequence analysis to assess the frequency of such variants in the sera of HCV genotype 1-infected patients not treated with HCV protease inhibitors.Here,we reviewed the literature on resistance variants of HCV protease inhibitors in treatment na?ve patients with chronic HCV genotype 1,as well as our experience.

Clostridium difficile infection in the community:Are proton pump inhibitors to blame?

Once a nosocomial disease,Clostridium difficile infection(CDI)now appears frequently in the community in the absence of exposure to antibiotics.Prior studies have shown that patients with community-acquired CDI are younger,more likely to be female,and have fewer comorbidities compared to patients with hospital-associated CDI.Because most studies of CDI are hospitalbased,comparatively little is known about communityacquired CDI.The recent study by Chitnis has received widespread attention because it used active surveillance to capture all cases of community-acquired CDI within a large population and assessed key risk factors.The authors found that low-level healthcare exposure and proton pump inhibitor use were common among those with non-antibiotics associated,community-acquired CDI.In this commentary,we discuss the changing epidemiology of community-acquired CDI and the evidence basis for the controversial association between proton pump inhibitors and community-acquired CDI.

复杂泥页岩地层井壁稳定钻井液材料研究现状

针对复杂泥页岩地层钻井过程中频繁出现的井壁失稳问题,目前国内外已形成了用于稳定井壁的钻井液技术,包括泥页岩水化抑制技术、地层孔隙封堵技术和化学固壁技术。但以上多种技术均无法抑制泥页岩的表面水化作用,高温条件下快速封堵和化学固壁剂的效果也相当有限,因此井壁失稳问题仍难以解决。系统总结了复杂泥页岩地层井壁稳定钻井液材料的研究工作,通过对井壁稳定钻井液材料研究现状进行分析,阐述了不同钻井液材料包括泥页岩水化抑制剂、封堵剂、化学固壁剂的作用机理,探讨了不同种类井壁稳定材料的优势和缺陷。据此指出开展泥页岩水化基础理论研究、开发高温高盐条件下稳定有效的新型纳米材料、建立能够模拟井下条件的化学固壁剂的评价方法将成为未来复杂泥页岩地层井壁稳定钻井液材料和技术研究的热点和难点。最后对复杂泥页岩地层井壁稳定钻井液技术和材料的发展方向进行了展望。

免疫检查点抑制剂联合抗血管生成药治疗乙型肝炎相关不可切除肝细胞癌的疗效及安全性

目的探讨免疫检查点抑制剂联合抗血管生成药治疗乙型肝炎相关不可切除肝细胞癌(unresectable hepatocellularcarcinoma,uHCC)的疗效及安全性。方法将2019年7月至2023年7月期间在首都医科大学附属北京佑安医院住院并接受免疫检查点抑制剂联合抗血管生成药治疗的85例乙型肝炎相关uHCC患者纳入研究,收集其临床资料,对疗效和安全性进行回顾性分析。结果85例uHCC患者中男性65例,女性20例,中位年龄60.0岁,中国肝癌分期方案(China Liver Cancer Staging,CNLC)Ⅲ期者54例(63.5%),血管侵犯者37例(43.5%),远处转移者37例(43.5%),肝功能Child-Pugh B~C级者共28例(32.9%)。经治疗6例(7.1%)完全缓解,28例(32.9%)部分缓解,客观应答率可达40.0%,中位无进展生存期为5.8个月(95%CI:4.0~7.7),中位总生存期为25.8个月(95%CI:16.4~35.2)。单因素分析显示年龄<55岁、Child-Pugh B~C级、有血管侵犯、CNLC分期Ⅲ~Ⅳ期患者的中位总生存期明显低于年龄≥55岁、Child-Pugh A级、无血管侵犯、CNLC分期Ⅰ~Ⅱ期的患者(P<0.05)。总体安全性良好,≥3级不良事件发生率为32.9%。结论免疫检查点抑制剂联合抗血管生成药治疗uHCC可延长患者的生存期,安全性良好。

含硅型碳酸钙垢防垢剂SMAA的研究

采用水溶液自由基共聚法,以次磷酸钠(SHP)、顺丁烯二酸酐(MA)、2-丙烯酰胺基-2-甲基-1-丙磺酸(AMPS)、乙烯基三甲氧基硅烷(A171)为原料、2,2′-偶氮双(2-甲基丙脒)二盐酸盐(V50)为引发剂,合成了一种新型含硅聚合物防垢剂SMAA,并利用FTIR、^(1)H NMR和XPS对其结构进行表征。结果表明,最优合成条件为:单体配比n(SHP)∶n(MA)∶n(AMPS)∶n(A171)=10∶30∶10∶1,引发剂加量为1.0%,反应温度为80℃,单体浓度为25%,聚合反应时间为5 h。在评价温度为70℃、加量为50 mg/L时,防垢率可达92.9%。利用SEM、XRD和TEM对防垢剂SMAA作用于碳酸钙的机理进行研究,防垢剂SMAA的防垢机理是使碳酸钙晶体发生晶格畸变,阻碍碳酸钙晶体的聚集增大,对已形成的碳酸钙微晶进行包覆。

不同脱水剂和催化剂对油酸基咪唑啉缓蚀性能的影响

选用二甲苯、活性氧化铝和硼酸等作为脱水剂或催化剂,分别合成了三种油酸基咪唑啉,利用红外光谱对咪唑啉的结构进行了表征,使用质量损失法、极化曲线法和交流阻抗法等技术比较了三种油酸基咪唑啉缓蚀剂在H_(2)S/CO_(2)饱和的高矿化度溶液中对碳钢的缓蚀性能。结果表明,使用活性氧化铝催化合成的咪唑啉缓蚀效果最好。

Synthesis,Biological Evaluation and Molecular Modeling of Cyclic Tetrapeptide Based Inhibitors HDAC

Histone deacetylases（HDACs） are considered to be among the most promising targets for the development of anti-cancer drugs,and HDAC inhibitors（HDACIs） have become a promising class of anti-cancer drugs.To explore whether thioacetyl group as the zinc binding group（ZBG） and a slight change in the hydrophobicity of the recognition domain of HDACIs could alter their activities,we synthesized a series of cyclo[-L-Am7（SAc）-Aib-L-Phe（n-Cl）D-Pro-] and evaluated their HDAC-inhibitory and antiproliferative activities.The results show that these peptides could inhibit HDAC at 10-9 mol/L level,and could selectively inhibit the proliferation of three human cancer cell lines with IC 50 at 10-6 mol/L level.Docking study was conducted to examine the mechanisms by which these peptides interact with HDAC2.It appeared that a zinc ion in the active site of HDAC was coordinated by the carbonyl oxygen atom of the ZBG in the inhibitor.Both the ZBG domain of all the peptides and the surface recognition domain of cyclo[-L-Am7（SAc）-Aib-L-Phe（o-Cl）-D-Pro-] and that of cyclo[-L-Am7（SAc）-Aib-L-Phe（m-Cl）-D-Pro-] interacted with HDAC2 via hydrogen bonding.Hydrophobic interaction has been considered to provide favorable contributions to stabilizing the complexes,and the introduction of a chlorine atom at the aromatic ring on the L-Phe position of these peptides affected the interaction between each of these inhibitors and the enzyme,resulting in slight change in the structure of the surface recognition domain of the peptides.

保水剂和蒸腾抑制剂对玉米生长和水肥耦合的影响

保水剂和蒸腾抑制剂的应用对玉米高效生产发挥着重要作用。为探究保水剂和蒸腾抑制剂对玉米生长和土壤水肥耦合的影响,在内蒙古自治区鄂尔多斯市乌审旗河南乡小石砭村进行田间试验。试验共设置4个处理,分别为灌水定额为30 mm并且施加保水剂(C1)、灌水定额为37.5 mm并且施加保水剂(C2)、灌水定额为45 mm并且施加蒸腾抑制剂(C3)和灌水定额为45 mm并且不施加试剂(CK)。结果表明:①保水剂和蒸腾抑制剂能有效提升土壤保水能力,与CK相比,C1、C2和C3处理下玉米生育期平均土壤含水率分别提升6.61%、11.94%和4.05%。②保水剂和蒸腾抑制剂能有效提升玉米株高,其中拔节期玉米株高提升率最高,C1、C2和C3较CK分别提升9.40%、17.45%和6.04%。③玉米的茎粗随着生育期的推进呈现出先快速增长后缓慢增长再略微减小的趋势,快速增长期为拔节期,拔节期相比于苗期茎粗平均增长率为60.21%。④保水剂的施加可以增加土壤肥力和土壤水肥之间的协同关系,C2相比于CK土壤全氮、有效磷、速效钾、缓效钾和有机质含量分别增加37.57%、82.76%、88.66%、1.31%和37.83%;土壤水肥耦合度和耦合协调度分别增加77.74%和52.79%。综上所述,施加保水剂和蒸腾抑制剂可有效改善土壤水分状况,促进玉米生长发育,较不施加任何试剂的处理有明显优势。

安罗替尼致高血压文献病例分析

目的探讨安罗替尼相关高血压的临床特点。方法检索中国知网、万方、PubMed、Web of Science数据库(截至2023年7月31日),收集安罗替尼相关高血压文献病例报告类文献,提取患者基本情况、安罗替尼用药情况、高血压情况、干预措施和转归等,进行描述性统计分析。结果纳入分析的文献为16篇,患者18例,男性8例,女性10例;年龄27~76岁,平均58岁;非小细胞肺癌13例,结缔组织和软组织恶性肿瘤2例,肝内胆管癌1例,卵巢癌1例,子宫癌1例。联用其他抗肿瘤药物4例;安罗替尼初始剂量均为12 mg/d。发生的高血压分级为1级3例(17%),2级4例(22%),3级9例(50%),4级2例(11%)。除8例患者从服用安罗替尼至发生高血压的时间不详外,其余10例患者从服用安罗替尼至发生高血压的时间在7 d~6个月内,中位时间36(30,42)d,其中7例(39%)发生在服用安罗替尼2个月内。18例患者中出现不同程度乏力6例(33%),头痛6例(33%),头晕5例(28%),呕吐3例(17%),视物模糊2例(11%),恶心1例(6%),抽搐1例(6%)。13例伴其他不良反应,其中手足综合征7例(39%),蛋白尿3例(17%),高脂血症3例(17%),可逆性后部白质脑病综合征2例(11%),癫痫1例(6%),便血1例(6%),皮疹1例(6%)。1~2级患者安罗替尼未调整(6例)或减量治疗(1例)后耐受良好;3~4级患者中,8例停用安罗替尼且接受降压药治疗,2例减量治疗,1例未调整,随访血压控制平稳。结论安罗替尼相关高血压多发生在用药2个月内,往往伴其他不良反应,3级以上高血压常见,但大多数患者经对症处理、停药或减量后转归良好。

Ce(NO_(3))_(3)和CeO_(2)纳米粒子对APTES膜耐腐蚀性的影响

目的通过对铜箔进行硅烷化处理,增强铜箔的耐腐蚀性能。方法采用化学浸泡法在9μm电解铜箔表面制备γ-氨丙基三乙氧基硅烷偶联剂(APTES)硅烷膜层、Ce^(3+)/APTES膜层、CeO_(2)/APTES膜层和Ce^(3+)/CeO_(2)/APTES膜层,对改性硅烷膜试样与空白试样进行接触角对照实验,对硅烷表面润湿性进行表征。在3.5%(质量分数)NaCl溶液中,对空白样、单一硅烷膜层、Ce^(3+)/APTES硅烷膜层和Ce^(3+)/CeO_(2)/APTES硅烷膜层进行浸泡实验和电化学实验,研究改性膜层前后的耐腐蚀性能。通过扫描电子显微镜(SEM)观察膜层表面形貌,并利用傅里叶变换红外光谱(FTIR)和X射线光电子能谱(XPS)对纳米粒子结构进行分析,探讨改性膜层的钝化机理。结果Ce(NO_(3))_(3)/CeO_(2)/APTES复合膜层的接触角最大,接触角为106.6°,表现出最佳的疏水性。同时,其表面的腐蚀坑数量和面积最小。在盐水浸泡和电化学实验中,各试样的腐蚀电流密度随着浸泡时间的延长而上升,Ce^(3+)/CeO_(2)/APTES试样的腐蚀电位发生正移,具有较低的腐蚀电流密度,并且该试样具有最高的相角和最高的阻抗值,远高于Ce^(3+)/APTES试样。结论与单一硅烷膜层和仅分别添加Ce(NO_(3))_(3)、CeO_(2)2种缓蚀剂的膜层相比,Ce(NO_(3))_(3)/CeO_(2)/APTES复合膜层的防护效果有明显提升,且Ce^(3+)与CeO_(2)之间的协同作用大大提高了硅烷膜层的耐腐蚀性能。

矿井高效抑尘剂优化配方及性能研究

以某煤矿掘进工作面粉尘为研究对象,开展矿井高效抑尘剂优化配方及性能研究。通过沉降实验,确定高效抑尘剂优化配方的润湿剂组分为2%的TX-100和0.5%的SDBS混合溶液;通过黏度测定实验,确定优化配方的黏结剂组分为E412;通过保水性实验,确定优化配方的保水抑尘剂组分为PAAS;通过抑尘剂溶液的酸碱度测定实验,确定选用PHOS调节溶液的pH值为6.8;最终研究得到矿井高效抑尘剂GHY-1配方组分及比例。性能测定实验结果表明:高效抑尘剂优化配方表面张力为68.15 mN/m,左、右接触角分别为11.25°和10.85°,黏度值为0.4mPa·s,保水率为80.5%,降尘效率可达95.3%。

我国胶磷矿浮选药剂研究进展

我国磷矿资源丰富,以难选的中低品位胶磷矿为主。泡沫浮选是分选此类磷矿最有效的方法,浮选药剂是浮选中最重要的影响因素之一。从介质调整剂、絮凝剂、起泡剂、抑制剂及捕收剂等方面综述了胶磷矿浮选药剂在选矿工艺、药剂开发及机理研究等方面的最新进展,重点归纳了国内外磷矿抑制剂和捕收剂的研究现状与热点。药剂分子间的协同效应、多功能基药剂合成及药剂复配在处理中低品位胶磷矿时表现出了良好的分选效果,研制新型绿色高效、经济环保的捕收剂和抑制剂将是胶磷矿浮选药剂的重要发展方向。

近5年国家谈判的抗肿瘤药纳入医保的品种及适应症变化分析

目的统计2019年到2023年五版国家医保目录协议期内谈判的抗肿瘤药品种的变化及医保限定的支付病种范围的变更,重点对单克隆抗体和蛋白激酶抑制剂的部分特殊品种的适应症变化进行分析。方法以表格的形式罗列出五版国家医保目录协议期内谈判的各类抗肿瘤药的品种个数、纳入年份及医保限定的支付病种范围。结果五版国家医保目录中协议期内谈判的抗肿瘤药的品种总数呈逐年递增趋势,各类抗肿瘤药的品种数排前3位的均是蛋白激酶抑制剂、单克隆抗体、其他类抗肿瘤药。医保限定的支付病种涵盖各个系统的肿瘤,如呼吸系统、消化系统、血液系统、泌尿系统、乳腺等,其中呼吸系统所占比例最高。部分品种连续5年均进入国家谈判药品目录。结论传统的抗肿瘤药由于不良反应大,患者无法耐受,近年来已逐渐被新型抗肿瘤药所替代。但由于新型抗肿瘤药价格昂贵,患者又需要长时间使用,故需要国家干预,尽可能降低价格,方能满足肿瘤患者的用药需求和可及性,从而减轻经济负担,提高生活质量。