莫西沙星和左氧氟沙星对耐多药肺结核患者空洞的改善和痰菌转阴的疗效比较

目的:比较莫西沙星和左氧氟沙星对耐多药肺结核(MDR-TB)患者空洞的改善和痰菌转阴的疗效。方法:选取2016年8月—2017年9月期间收治的MDR-TB患者66例资料,按治疗方法的不同将其分为观察组和参照组(每组33例);观察组患者给予盐酸莫西沙星片口服治疗,参照组患者给予盐酸左氧氟沙星胶囊口服治疗,比较两组患者治疗后空洞的改善率和痰菌转阴率的差异。结果:观察组患者治疗后空洞的改善率为96.97%明显高于参照组为78.79%(P<0.05),痰菌转阴率为96.97%明显高于参照组为75.76%(P<0.05)。结论:采用莫西沙星治疗MDR-TB患者的疗效优于左氧氟沙星,有效促进了患者空洞的改善和痰菌的转阴。     

miR-125b、miR-29a和miR-155-5p作为诊断结核性脑膜炎生物标志的研究

目的 探讨结核性脑膜炎患者脑脊液及血浆中 microRNA (miR)-125b、 miR-29a 和 miR-155-5p 的表达水平及其临床意义。方法 收集 20 例结核性脑膜炎患者（结脑组）和 20 例原发性头痛患者（对照组）的脑脊液和血浆, 分别提取总 RNA, 使用实时定量 PCR 方法分别检测脑脊液和血浆中 miR-125b、 miR-29a 及 miR-155-5p 的表达水平。结果 与对照组相比, 结脑组脑脊液、 血浆中 miR-29a、 miR-125b 表达水平明显上调, 结脑组血浆中 miR-155-5p 表达水平明显上调, 差异均有统计学意义 （均 P<0.01）, 而 2 组脑脊液中 miR-155-5p 表达水平比较差异无统计学意义。结论 miR-125b、 miR-29a 和 miR-155-5p 可能参与了调节结核性脑膜炎的发生、 发展过程, miR-125b和 miR-29a有可能作为潜在的诊断结核性脑膜炎的生物学标志。     

miR-130b与碘难治性分化型甲状腺癌的关系研究

目的探讨miR-130b与碘难治性分化型甲状腺癌(RR-DTC)的关系。方法选取2013年1月至2015年12月在我院就诊并行~(131)I照射治疗的远处转移DTC患者104例,随访36个月,根据治疗结果,将患者分为RR-DTC组(41例)和碘治疗有效组(R-DTC组)(63例),检测患者~(131)I照射治疗前肿瘤组织miR-130b的表达水平,观察患者血清甲状腺球蛋白(Tg)的变化趋势及其与miR-130b的相关性。结果①~(131)I照射治疗前,R-DTC组和RR-DTC组患者肿瘤组织中miR-130b水平分别为(0.79±0.10)和(0.43±0.07),RR-DTC组患者miR-130b水平明显低于R-DTC组,而血清Tg水平高于R-DTC组(P<0.05)。治疗后,RR-DTC组患者Tg同比下降率和T/B分别为10.13%±9.87%和4.29%±1.64%,明显低于R-DTC组(P<0.05)。②Spearman相关性分析显示,Tg同比下降率、T/B与miR-130b呈正相关性(r_s=0.928、0.896,P<0.05)。③ROC曲线分析显示,miR-130b诊断RR-DTC的截断值为0.485,曲线下面积为0.662。根据miR-130b的截断值,将RR-DTC组患者分为<0.485亚组(23例)和≥0.485亚组(18例)。④随访期间,<0.485亚组和≥0.485亚组RR-DTC患者3年生存率分别为34.78%、50.0%,经Log-rank检验,差异无统计学意义(P>0.05)。结论甲状腺癌组织miR-130b表达有望成为难治性分化型甲状腺癌潜在的辅助诊断指标之一。     

莫西沙星联合结核丸治疗耐多药肺结核的临床观察

目的:观察莫西沙星联合结核丸治疗耐多药肺结核的疗效和安全性。方法:116例耐多药肺结核患者随机均分为对照组和观察组。对照组患者给予盐酸莫西沙星片0.4g,口服,每日1次;观察组患者在对照组治疗的基础上给予结核丸9 g,口服,每日2次;同时两组患者均给予利福喷丁、丙硫异烟肼、阿米卡星、帕司烟肼、吡嗪酰胺、对氨基水杨酸等常规药物治疗;两组患者疗程均为18个月。观察两组患者的临床疗效,治疗前及治疗6、12、18个月后的T细胞亚群(CD_3~+,CD_4~+,CD_4~+/CD_8~+)、干扰素(INF)γ、白细胞介素(IL)4水平及不良反应发生情况。结果:观察组患者总有效率显著高于对照组,差异有统计学意义(P<0.05)。治疗后,两组患者CD_3~+、CD_4~+、CD_4~+/CD_8~+、INF-γ水平均显著高于同组治疗前,且随时间逐渐升高,观察组高于对照组;IL-4水平显著低于同组治疗前,且随时间逐渐降低,观察组低于对照组,差异均有统计学意义(P<0.05);两组患者不良反应发生率比较,差异无统计学意义(P>0.05)。结论:在常规治疗的基础上,莫西沙星联合结核丸治疗耐多药肺结核的疗效显著优于单用莫西沙星,且安全性相当。     

不同类型喹诺酮类药物治疗老年耐多药结核的临床疗效对比分析

目的探讨不同类型喹诺酮类药物治疗老年耐多药结核的疗效和安全性。方法收集2014年12月~2015年12月我院诊断为耐多药结核的老年患者作为研究对象,按患者接受喹诺酮类的药物种类分为:莫西沙星组60例、环丙沙星组56例和左氧氟沙星组58例。对比(1)莫西沙星组、环丙沙星组与左氧氟沙星组治疗多耐药结核的临床疗效。(2)莫西沙星组、环丙沙星组与左氧氟沙星组对结核杆菌清除率。(3)莫西沙星组、环丙沙星组与左氧氟沙星组不良反应发生率。结果 (1)莫西沙星组、环丙沙星组、左氧氟沙星组临床有效率分别为88.5%、76.8%、70.7%。莫西沙星组与环丙沙星、左氧氟沙星组有效率比较,差异有统计学意义(P<0.05)。环丙沙星、左氧氟沙星组有效率比较,差异无统计学意义(P>0.05)。(2)莫西沙星组、环丙沙星组、左氧氟沙星组在治疗4、8、12周时对结核杆菌清除率分别为59.2%、75%、90.6%、(21.4%、55.4%、87.5%)、(20%、53.3%、77.8%),以莫西沙星清除率最高,差异有统计学意义(P<0.05)。(3)莫西沙星组、环丙沙星组与左氧氟沙星组不良反应发生率比较,差异无统计学意义(P>0.05)。结论相对于环丙沙星、左氧氟沙星,莫西沙星对老年多耐药结核的清除率更高,疗效肯定,而且安全性好。     

莫西沙星在治疗耐多药肺结核病中的临床效果分析

目的 观查莫西沙星联合其他抗结核药物治疗耐多药肺结核病(MDR-TB)的临床疗效.方法 将106例MDR-TB患者,随机分为观察组和对照组,每组各53例,两组均进行常规抗结核药物治疗,观察组患者口服莫西沙星片1日0.4g,对照组患者口服左氧氟沙星片1日0.5g,两组治疗周期为18个月,治疗结束后,观察两组患者临床疗效、肺部病灶明显吸收率与空洞闭合率、痰菌阴转率、不良反应发生情况.结果 治疗结束后,观察组患者临床总有效率(90.57%)、病灶明显吸收率(73.58%)、空洞闭合率(75.47%)、痰菌转阴率(92.45%),显著高于对照组(75.47%、45.28%、47.17%、71.10%),差异均有统计学意义(P<0.05);观察组不良反应发生率显著低于对照组,差异均有统计学意义(P<0.05).结论 莫西沙星联合其他抗结核药物,对MDR-TB患者进行治疗,临床疗效显著,值得临床推广应用.     

miR-10b、miR145及miR155在乳腺癌患中的表达及临床意义

目的 探讨microRNA-10b(miR-10b)、microRNA-145(miR-145)及microRNA-155(miR-155)在乳腺癌患者病理组织及血清中的表达水平,进而评价其在乳腺癌诊断中的价值.方法 收集100例正常健康志愿者,150例乳腺癌患者血液和39例乳腺癌患者的癌组织和癌旁组织,提取血液和组织中的microRNA,采用实时荧光定量PCR检测miR-10b、miR-145及miR-155表达水平,分析其与乳腺癌患者临床病理参数之间的相关性,并绘制ROC曲线分析其在乳腺癌诊断中的价值.结果 治疗前乳腺癌患者血清中的miR-10b,miR-145和miR-155表达水平高于对照组(P＜0.05),三者表达水平均与肿瘤转移显著相关,与年龄、组织学特征、ER表达无相关性(P＞0.05)miR-10 b与临床分期显著相关(P＜0.05),miR-10b的ROC曲线下面积为0.936,miR-145的ROC曲线下面积为0.904,miR-155的ROC曲线下面积为0.91.miR-10b,miR-145,miR155在Ⅲ级乳腺癌患者肿瘤组织的表达水平明显高于Ⅰ～Ⅱ级乳腺癌患者癌组织的表达水平(P＜0.05).结论 血清中miR-10 b、miR-145及miR-155有可能作为乳腺癌早期诊断的肿瘤标志物.     

莫西沙星与头孢哌酮舒巴坦治疗老年心力衰竭患者铜绿假单胞菌院内感染的疗效对比观察

目的 探讨莫西沙星与头孢哌酮舒巴坦治疗老年心力衰竭患者铜绿假单胞菌(PA)院内感染的临床疗效及安全性.方法 64例心力衰竭合并下呼吸道PA感染的老年患者按单纯随机分为两组,各32例.对照组给予头孢哌酮舒巴坦治疗,观察组予以莫西沙星治疗,观察两组患者治疗有效率、病原菌清除率、症状消失时间、免疫功能以及不良反应发生率.结果 观察组总有效率93.75％,对照组81.25％,差异无统计学意义(P>0.05);观察组病原菌清除率90.62％,明显高于对照组68.75％,差异有统计学意义(P<0.05);观察组患者体温恢复时间、咳嗽消失时间、湿啰音消失时间、白细胞数恢复时间均低于对照组,差异有统计学意义(P<0.05);观察组CD3+、CD4+、CD4+/CD8+及NK细胞水平高于对照组,CD8+水平低于对照组,差异有统计学意义(P<0.05);观察组不良反应发生率为18.75％,与对照组21.88％类似,差异无统计学意义(P>0.05).结论 与头孢哌酮舒巴坦比较,莫西沙星对老年心力衰竭患者PA院内感染疗效显著,安全性同等,值得临床推广应用.     

莫西沙星治疗成人支原体肺炎的临床疗效分析

目的评价莫西沙星在支原体肺炎治疗中的有效性。方法连续收集我院呼吸科确诊的86例社区获得性肺炎(支原体肺炎)患者,选择其中初始治疗采用莫西沙星治疗的28例患者(莫西沙星组)和采用头孢呋辛联合阿奇霉素治疗的22例患者(对照组),比较莫西沙星在成人支原体肺炎治疗中的临床疗效。结果莫西沙星组与对照组均无治疗失败病例,莫西沙星组72 h退热率优于对照组(75.0%vs.45.5%),平均热退时间短于对照组(3.07 d vs.5.23 d),获得临床稳定所需时间短于对照组(2.54 d vs.4.10 d,P<0.05),静脉应用抗生素疗程短于对照组(8.61 d vs.11.41 d,P<0.05)。两组总的抗生素疗程和住院天数差异无统计学意义。结论莫西沙星与对照组治疗成人支原体肺炎的临床有效率相似,但莫西沙星组退热快,72 h退热率高,获得临床稳定所需时间短,静脉应用抗生素疗程短。     

热毒宁联合莫西沙星治疗社区获得性肺炎50例

目的 研究热毒宁注射液联合盐酸莫西沙星氯化钠注射液治疗社区获得性肺炎的临床疗效.方法 本院收治的社区获得性肺炎患者100例,分为观察组和对照组.对照组给予盐酸莫西沙星氯化钠注射液治疗,观察组给予热毒宁注射液联合盐酸莫西沙星氯化钠注射液治疗.结果 观察组总有效率94.00%高于对照组80.00%,差异有统计学意义(P<0.05).观察组第3天白细胞总数正常率高于对照组,差异显著(P<0.05).结论 热毒宁注射液联合盐酸莫西沙星氯化钠注射液治疗社区获得性肺炎患者疗效可靠.     

Analysis of γβ, βγ, γγ, ββ multiple turns in proteins

Abstract: The number of γ‐turns in a representative protein dataset selected from the current Protein Data Bank has increased almost seven times during the past decade. Eighty percent classic γ‐turns and 57% inverse γ‐turns are associated as multiple turns with either another γ‐turn or a β‐turn. We refer to these as multiple turns of the (γβ)_1,2,3 or (βγ)_1,2,3 type, depending upon whether the γ‐turn is before or after the β‐turn along the protein chain, respectively. However, for multiple turns involving only γ‐turns, we follow the nomenclature analogous to that proposed earlier for the multiple (or double) β‐turns. Fifty‐eight per cent β‐turns are associated as multiple turns with another β‐turn. We extracted multiple turns from the protein dataset and classified them on the basis of individual γ‐ or β‐turn types and the number of overlapping residues. Furthermore, we evaluated the amino acid positional potentials and determined the statistically significant amino acid preferences, hydrogen bond/side‐chain interaction preferences in the multiple turns and secondary structure preferences for residues immediately flanking these turns. The results of our analysis would be useful in the modeling, prediction or design of multiple turns in proteins. The amino acid sequence corresponding to the multiple turn, position in the protein chain, PDB Code/chain in which multiple turn is present and the individual turn types constituting the multiple turns are available from our website and this information would also be integrated in our Database of Structural Motifs in Proteins ( http://www.cdfd.org.in/dsmp.html ).     

Analysis of γβ, βγ, γγ, ββ continuous turns in proteins

Abstract: We report the observation of continuous turns in proteins which comprise individual γ‐turns or β‐turns or both that are situated immediately one after the other along the polypeptide chain. The continuous turns were identified from a representative data set of three‐dimensional protein crystal structures. The γβ/βγ, γγ and ββ continuous turns represent peptides of varying amino acid residue lengths and conformations. The continuous turns frequently observed in proteins were: γβ, between a coil and a strand; βγ, between a helix and a strand; γγ, between coils; and ββ, either between a strand and a coil or between strands or coils. We determined the statistically significant amino acid residue preferences at individual positions in the turn, calculated amino acid positional potentials and analyzed main chain hydrogen bonds and side‐chain interactions likely to stabilize the continuous turns. The data on continuous turns have been integrated in the database of structural motifs in proteins (DSMP) on our web server at ( http://www.cdfd.org.in/dsmp.html ). This is useful to make queries on sequences compatible with different continuous turns.     

Synthese von γ,γ'-Dihydroxysulfonen und γ-Hydroxy-γ'-ketosulfonen

Syntheses of γ,γ'-Dihydroxysulfones and γ-Hydroxy-γ'-ketosulfones Reduction of γ,γ'-diketosulfones 1 with dimethylaminoborane leads to γ,γ'-dihydroxysulfones 3 via γ-hydroxy-γ'-ketosulfones 2 . The influence of substituents on the ratio of the yields of 2 and 3 is investigated.     

Synthesis of β and γ-fluorenylmethyl esters of respectively Nα-Boc-L-aspartic acid and Nα-Boc-L-glutamic acid

The orthogonal synthesis of N^x-Boc-L-aspartic acid-γ-fluorenylmethyl ester and N^α-Boc-L-glutamic acid-δ-fluorenylmethyl ester is reported. This is a four-step synthesis that relies on the selective esterification of the side-chain carboxyl groups on N^x-CBZ-l -aspartic acid and N^α-CBZ-l -glutamic acid. Such selectivity is accomplished by initially protecting the a-carboxyl group through the formation of the corresponding 5-oxo-4-oxazolidinone ring. Following side-chain esterification, the α-carboxyl and α-amino groups are deprotected with acidolysis. Finally, the α-amino group is reprotected with the t-butyl-oxycarbonyl (Boc) group. Thus aspartic acid and glutamic acid have their side-chain carboxyl groups protected with the base-labile fluorenylmethyl ester (OFm) and their α-amino groups protected with the acid-labile Boc group. These residues, when used in conjunction with N^x-Boc-N^ε-Fmoc-l -lysine, are important in the formation of side-chain to side-chain cyclizations, via an amide bridge, during solid-phase peptide synthesis.     

Conformational investigation of α, β-dehydropeptides

The crystal structure of Ac-Pro-ΔVal-NHCH₃ was examined to determine the influence of the α,β-dehydrovaline residue on the nature of peptide conformation. The peptide crystallizes from methanol-diethyl ether solution at 4° in needle-shaped form in orthorhombic space group P2₁2₁2₁ with a= 11.384(2) Å, b = 13.277(2) Å, c = 9.942(1) Å. V = 1502.7(4) ų Z = 4, D_m= 1.17 g cm^?3 and D_c=1.18 g cm^?3 The structure was solved by direct methods using SHELXS-86 and refined to an R value of 0.057 for 1922 observed reflections. The peptide is found to adopt a β-bend between the type I and the type III conformation with φ₁=?68.3(4)°, ψ₁=? 20.1(4)°, φ₂=?73.5(4)°= and Ψ₂=?14.1(4)°=. An intramolecular hydrogen bond between the carbonyl oxygen of ith residue and the NH of (i+ 3)th residue stabilizes the β-bend. An additional intermolecular N.,.O hydrogen bond joins molecules into infinite chains. In the literature described crystal structures of peptides having a single α,β-dehydroamino acid residue in the (i+ 2) position and forming a β-bend reveal a type II conformation.     

Conformational investigation of α,β-dehydropeptides

Conformations of three series of model peptides: homochiral Ac-Pro-L-Xaa-NHCH₃ and heterochiral Ac-Pro-D-Xaa-NHCH₃ (Xaa=Phe, Val, Leu. Abu. Ala) as ivell as α,β-dehydro Ac-Pro-ΔXaa-NHCH_s [ΔXaa = (Z)-ΔPhe, ΔVal. (Z)-ΔLeu, (Z)-ΔAbu] were investigated by CD spectroscopy in 2 % dichloromethanecyclohexane, trifluoroethanol. water. and occasionally in other solvents. The spectra of homochiral peptides show a significant solvent dependence. Folded structures are present in 2% dichloromethane-cyclohexane and unordered ones occur in water. The folded conformers are of the inverse γ-turn type for all the peptides but Ac-Pro-L-Phe-NHCH₃ for which the type-I β-turn is preferred. The changes in the spectra of the heterochiral peptides are limited. The compounds adopt the typc-II β–turn in 2% dichloromethanecyclohexane, represented by class B spectra, and retain this conformation in water as well as in fluorinated alcohols but not always to a full extent. The CD spectra of the unsaturated peptides in 2%, dichloromethanecyclohexane, although they cannot be assigned to any common spectral class, must be attributed to the βII-turn conformation as determined for these coinpounds by NMR and IR spectroscopy. The CD spectra of dehydropeptides exhibit a considerable solvent dependence and suggest unordered structures in water.     

Conformational investigation of αβ-dehydropeptides

Solution conformations of three series of model peptides, homochiral Ac-Pro-L-Xaa-NHCH₃ and heterochiral Ac-Pro-D-Xaa-NHcH₃ (Xaa = Val, Phe, Leu, Abu. Ah) as well as αβ-unsaturated Ac-Pro-ΔXaa-NHCH₃ [Δ Xaa =ΔVal, (Z)-ΔPhe, (Z)-ΔLeu, (Z)-ΔAbu] were investigated in CDCl₃ and CH₂Cl₂ by ¹H-, ¹³C-NMR, and FTIR spectroscopy. NH stretching absorption spectra, solvent shifts Δδ for NH (Xaa) and NHCH₃ on going from CDCl₃ to (CD₃)₂SO, diagnostic interresidue proton NOEs, and trans-cis isomer ratios were examined. These studies performed showed the essential difference in conformational propensities between homochiral peptides (L-Xaa) on the one hand and heterochiral (D-Xaa) and αβ-dehydropeptides (ΔXaa) on the other. Former compounds are conformationally flexible with an inverse γ-bend, a β-turn, and open forms in an equilibrium depending on the nature of the Xaa side chain. Conformational preferences of heterochiral and αβ-dehydropeptides are very similar, with the type-II β-turn as the dominating structure. There is no apparent correlation between conformational properties and the nature of the Xaa side chain within the two groups. The β-turn formation propensity seems to be somewhat greater in αβ-unsaturated than in heterochiral peptides, but an estimation of β-folded conformers is risky.     

Properties of a Resiniferatoxin-stimulated,Calcium Inhibited but Phosphatidylserine-dependent Kinase,which is Distinct from Protein Kinase C Isotypes α, β1γ, δ, ε and η

We have separated a resiniferatoxin-stimulated histone-kinase activity from human neutrophils, elicited mouse macrophages and murine alveolar macrophages by hydroxyapatite chromatography. The assay conditions for resiniferatoxin kinase were optimized as part of this study and in the presence of phosphatidylserine but absence of Ca²⁺ the K_a for histone IIIs phosphorylation by resiniferatoxin was calculated as 16 nm . Using a phosphate gradient of 20–500 mm , peaks of protein kinase C activity could be washed from the hydroxyapatite column in 300 nm phosphate and resiniferatoxin kinase recovered in 500 mm phosphate. At the optimum concentration of 160 nm , the ability of resiniferatoxin to induce enzyme activity was compared with a range of phorbol esters all at the same concentration. These related compounds failed to activate resiniferatoxin kinase although they have previously been shown to activate protein kinase C isotypes. Similarly sn-1,2,-dioleoylglycerol and the potent irritant capsaicin at 30 μm failed to activate the kinase. A Scatchard analysis of [³H] phorbol dibutyrate binding produced a linear plot (K_d 41·6 nm ; B_max 11·6 fmol unit^?1) and binding was inhibited by resiniferatoxin and 12-O-tetradecanoylphorbol-13-acetate (TPA), with resiniferatoxin 700 times more potent than TPA in this respect. A radiolabeled resiniferatoxin binding assay was also used to demonstrate specific binding of [³H]resiniferatoxin which could be inhibited by unlabelled compound. Resiniferatoxin kinase activity was shown to be distinct from the protein kinase C isotypes α, β₁, γ δ and ε by means of immunological analysis and from the η isotype, because that isotype was not stimulated by resiniferatoxin but was stimulated by TPA when a pseudosubstrate was used. In addition the resiniferatoxin-stimulated activity was inhibited in-vitro by the addition of Ca²⁺ (K_i 0·1-0·5 nm free Ca²⁺). Further purification of resiniferatoxin kinase by Superose chromatography indicated a major activity fraction of about 70–90 kDa. Thus resiniferatoxin kinase, isolated from human and mouse inflammatory cells is distinct from the known isotypes of protein kinase C and is a major resiniferatoxin receptor.     

Separation of δ-, γ- and α-tocopherols by CEC

In this study capillary electrochromatography (CEC) was used for the separation of three tocopherols (TOHs), namely delta-, gamma- and alpha-TOH and the antioxidant compound, butylated hydroxytoluene (BHT). The CEC experiments were carried out using an octadecylsilica (ODS) stationary phase packed, in our laboratory, in a fused-silica capillary (100 microm I.D., 365 microm O.D. x 33 cm of total length and 24.6 or 8.4 cm effective length). The mobile phase was composed by a mixture of methanol (MeOH) and acetonitrile (ACN), at different concentrations and 0.01% (w/v) of ammonium acetate. Retention time (t(R)), retention factor (k), resolution (R(s)) of the three TOHs were strongly influenced by the organic solvent composition of the run buffer and by the effective length of the capillary. Optimum experimental conditions were found even employing the short effective length of the capillary achieving the baseline separation of the studied analytes in a relatively short time (less than 5 min). The optimized method was applied to the qualitative analysis of vitamin E (alpha-TOH) present in a human serum extract.