The superiority of PMFs on reversing drug resistance of colon cancer and the effect on aerobic glycolysis-ROS-autophagy signaling axis

Background:Polymethoxylatedflavones(PMFs)are compounds present in citrus peels and other Rutaceae plants,which exhibit diverse biological activities,including robust antitumor and antioxidant effects.However,the mechanism of PMFs in reversing drug resistance to colon cancer remains unknown.In the present study,we aimed to investigate the potential connection between the aerobic glycolysis-ROS-autophagy signaling axis and the reversal of PTX resistance in colon cancer by PMFs.Methods:MTT Cell viability assay and colony formation assay were used to investigate the effect of PMFs combined with PTX in reversing HCT8/T cell resistance ex vivo;the mRNA and protein levels of the target were detected by SDS-PAGE(sodium dodecyl sulfate-polyacrylamide gel electrophoresis),quantitative real-timefluorescence polymerase chain reaction(qRT-PCR)and Western blot protein immunoblotting(WB);An HCT8/T cell xenograft model was established to investigate the MDR reversal activity of PMFs in vivo;The extracellular acidification rate(ECAR)and the oxygen consumption rate(OCR)were detected to assess the cellular oxygen consumption rate and glycolytic process.Results:HCT8/T cells demonstrated significant resistance to PTX,up-regulating the expression levels of ABCB1 mRNA,P-gp,LC3-I,and LC3-II protein,and increasing intracellular reactive oxygen species(ROS)content.PMFs mainly contain two active ingredients,nobiletin,and tangeretin,which were able to reverse drug resistance in HCT8/T cells in a concentration-dependent manner.PMFs exhibited high tolerance in the HCT8/T nude mouse model while increasing the sensitivity of PTX-resistant cells and suppressing tumor growth significantly.PMFs combined with PTX reduced extracellular acidification rate(ECAR)and oxygen consumption rate(OCR)in HCT8/T cells.Additionally,PMFs reduced intracellular ROS content,down-regulated the expression levels of autophagy-related proteins LC3-I,LC3-II,Beclin1,and ATG7,and significantly reduced the number of autophagosomes in HCT8/T cells.Conclusions:The present study demonstrated that PMFs could potentially reverse PTX resistance in colon cancer by regulating the aerobic glycolysis-ROS-autophagy signaling axis,which indicated that PMFs would be potential potentiators for future chemotherapeutic agents in colon cancer.

Research progress in tumor angiogenesis and drug resistance in breast cancer

Angiogenesis is considered a hallmark pathophysiological process in tumor development. Aberrant vasculature resulting from tumor angiogenesis plays a critical role in the development of resistance to breast cancer treatments, via exacerbation of tumor hypoxia, decreased effective drug concentrations within tumors, and immune-related mechanisms. Antiangiogenic therapy can counteract these breast cancer resistance factors by promoting tumor vascular normalization. The combination of antiangiogenic therapy with chemotherapy, targeted therapy, or immunotherapy has emerged as a promising approach for overcoming drug resistance in breast cancer. This review examines the mechanisms associated with angiogenesis and the interactions among tumor angiogenesis, the hypoxic tumor microenvironment, drug distribution, and immune mechanisms in breast cancer. Furthermore, this review provides a comprehensive summary of specific antiangiogenic drugs, and relevant studies assessing the reversal of drug resistance in breast cancer. The potential mechanisms underlying these interventions are discussed, and prospects for the clinical application of antiangiogenic therapy to overcome breast cancer treatment resistance are highlighted.

Activation of STAT3 signaling in human stomach adenocarcinoma drug-resistant cell line and its relationship with expression of vascular endothelial growth factor

AIM: To investigate the difference in activation of STAT3 signaling between two human stomach adenocarcinoma cell lines: 5-fluorouracil resistant cell line and its parental cell line, and to evaluate its relationship with the expression of vascular endothelial growth factor (VEGF). METHODS: Western blot and electrophoretic mobility shift assay (EMSA) were used to detect the expression of phospho-STAT3 protein and constitutive activation of STAT3 in two human stomach adenocarcinoma cell lines, 5-fluorouracil resistant cell line SGC7901/R and its parental cell line SGC7901, respectively. The mRNA expression of VEGF was analysed by semi-quantitative RT-PCR. The expressive intensity of VEGF protein was measured by immunocytochemistry. RESULTS: The expressions of phospho-STATS protein and constitutive activation of STAT3 between two human stomach adenocarcinoma cell lines were different. Compared with the parental cell line SGC7901, the STAT3DNA binding activity and the expressive intensity of phospho-STAT3 protein were lower in the drug-resistant cell line SGC7901/R. The expression levels of VEGF mRNA and its encoded protein were also decreased in drugresistant cell line. CONCLUSION: Over-expression of VEGF may be correlated with elevated STAT3 activation in parental cell line. Lower VEGF expression may be correlated with decreased STAT3 activation in resistant cell line, which may have resulted from negative feedback regulation of STAT signaling.

BanXiaXieXin decoction treating gastritis mice with drug-resistant Helicobacter pylori and its mechanism

BACKGROUND Helicobacter pylori(H.pylori)is the main pathogen that causes a variety of upper digestive diseases.The drug resistance rate of H.pylori is increasingly higher,and the eradication rate is increasingly lower.The antimicrobial resistance of H.pylori is an urgent global problem.It has been confirmed that Banxia Xiexin decoction(BXXXT)demonstrates the effects of treating gastrointestinal diseases,inhibiting H.pylori and protecting gastric mucosa.The purpose of the present study is to further explore the therapeutic effects of BXXXT on drug-resistant H.pylori.AIM To confirm that BXXXT demonstrates therapeutical effects in vivo and in vitro on gastritis mice with drug-resistant H.pylori and explain its mechanism to provide an experimental basis for promoting the application of BXXXT.METHODS The aqueous extract of BXXXT was gained by water decocting method.The inhibitory effect of the aqueous extract on H.pylori was detected by dilution in vitro;drug-resistant H.pylori cells were used to build an acute gastritis model in vivo.Thereafter,the model mice were treated with the aqueous extract of BXXXT.The amount of H.pylori colonization,the repair of gastric mucosal damage,changes of inflammatory factors,apoptosis,etc.,were assessed.In terms of mechanism exploration,the main medicinal compositions of BXXXT aqueous extract and the synergistic bacteriostatic effects they had demonstrated were analyzed using mass spectrometry;the immune function of peripheral blood cells such as CD3+T and CD4+T of mice with gastritis before and after treatment with BXXXT aqueous extract was detected using a flow cytometry;the H.pylori transcriptome and proteome after treatment with BXXXT aqueous extract were detected.Differently expressed genes were screened and verification was performed thereon with knockout expression.RESULTS The minimum inhibitory concentration of BXXXT aqueous extract against H.pylori was 256-512μg/mL.A dose of 28 mg/kg BXXXT aqueous extract treatment produced better therapeutical effects than the standard triple therapy did;the BXXXT aqueous extract have at least 11 ingredients inhibiting H.pylori,including berberine,quercetin,baicalin,luteolin,gallic acid,rosmarinic acid,aloe emodin,etc.,of which berberine,aloe emodin,luteolin and gallic acid have a synergistic effect;BXXXT aqueous extract was found to stimulate the expressions of CD3+T and CD4+T and increase the number of CD4+T/CD8+T in gastritis mice;the detection of transcriptome and proteome,quantitative polymerase chain reaction,Western blotting and knockout verification revealed that the main targets of BXXXT aqueous extract are CFAs related to urea enzymes,and CagA,VacA,etc.CONCLUSION BXXXT aqueous extract could demonstrate good therapeutic effects on drug-resistance H.pylori in vitro and in vivo and its mechanism comes down to the synergistic or additional antibacterial effects of berberine,emodin and luteolin,the main components of the extract;the extract could activate the immune function and enhance bactericidal effects;BXXXT aqueous extract,with main targets of BXXXT aqueous extract related to urease,virulence factors,etc.,could reduce the urease and virulence of H.pylori,weaken its colonization,and reduce its inflammatory damage to the gastric mucosa.

Taxotere resistance in SUIT Taxotere resistance in pancreatic carcinoma cell line SUIT 2 and its sublines

AIM: To investigate the specific mechanisms of intrinsic and acquired resistance to taxotere (TXT) in pancreatic adenocarcinoma (PAC). METHODS: MTT assay was used to detect the sensitivity of PAC cell line SUIT-2 and its sublines (S-007, S-013, S-020, S-028 and TXT selected SUIT-2 cell line, S2/TXT) to TXT. Mdr1 (P-gp), multidrug resistance associated protein (MRP), lung resistance protein (LRP) and beta-tubulin isotype gene expressions were detected by RT-PCR. The functionality of P-gp and MRP was tested using their specific blocker verapamil (Ver) and indomethacin (IMC), respectively. The transporter activity of P-gp was also confirmed by Rhodamine 123 accumulation assay. RESULTS: S-020 and S2/TXT were found to be significantly resistant to TXT(19 and 9.5-fold to their parental cell line SUIT-2, respectively). RT-PCR demonstrated strong expression of Mdr1 in these two cell lines, but weaker expression or no expression in other cells lines. MRP and LRP expressions were found in most of these cell lines. The TXT-resistance in S2-020 and S2/TXT could be reversed almost completely by Ver, but not by IMC. Flow cytometry showed that Ver increased the accumulation of Rhodamine-123 in these two cell lines. Compared with S-020 and SUIT-2, the levels of beta-tubulin isotype II, III expressions in S-2/TXT were increased remarkably. CONCLUSION: The both intrinsic and acquired TXT-related drug resistance in these PAC cell lines is mainly mediated by P-gp, but had no relationship to MRP and LRP expressions. The increases of beta-tubulin isotype II, III might be collateral changes that occur when the SUIT-2 cells are treated with TXT.

Gap Junctional Intercellular Communication Increases Cytotoxicity and Reduces Resistance to Hydroxyurea

Background: Gap junctions enable small molecules to diffuse between adjacent cells and have been associated with greater cytotoxicity of radiation and anti-cancer drugs. We investigated?whether this gap junctional intercellular communication (GJIC) affected the cytotoxicity of the classic?ribonucleotide reductase (RR) inhibitor and anti-cancer agent, hydroxyurea (HU). Materials and Methods: We used GJIC-proficient and deficient, connexin 43-expressing WB rat liver epithelial cell lines. We compared HU toxicity by crystal violet assay, effects of the drug on deoxynucleotide pools by HPLC, and ability of GJIC to increase toxicity of HU-resistant cells through a bystander effect in co-culture experiments. Results: GJIC-proficient cells were three- to five-fold more sensitive (IC50?0.1 mM) to HU than GJIC-deficient derivatives (IC50?0.3 - 0.5 mM). This sensitivity depended upon GJIC because treatment of GJIC-proficient cells with the GJIC blocker oleamide decreased HU toxicity by approximately 60% - 80% and restoration of GJIC in GJIC-deficient cells by stable transduction of connexin 32-encoding?Gjb1?increased HU toxicity (IC500.1 mM). The effects were not due to connexin expression?per se?or its localization since all cell lines expressed comparable quantities of connexin 43 that was localized to the plasma membrane. Also HU sensitivity was not related to differential effects on nucleotide metabolism in the cells. Thymidine triphosphate levels increased and deoxyadenosine triphosphate levels decreased similarly (15% - 20%) in GJIC-proficient and deficient cells over 24 h of HU treatment. More importantly, when HU-resistant cells were co-cultured with sensitive cells, the resistant cells were killed only when GJIC?was present. Conclusion: The data suggest that GJIC enhances cytotoxicity and decreases resistance?to HU. These results may be important clinically if GJIC can be enhanced in drug-resistant cells.

抗菌压电材料:对细菌无选择性杀伤和不产生细菌耐药性

背景:压电材料可通过催化作用产生活性氧,通过多种途径来破坏细菌,而且不会导致细菌产生耐药性。这种不依赖抗生素的抗菌方式具有明显的优势,可以对细菌进行无差别的杀伤,为今后的抗菌策略提供了一种新思路。目的:文章主要总结了有关压电材料特性与抗菌机制,并讨论了部分压电材料在抗菌领域的研究现状。方法:在Pub Med、Web of Science、中国知网和万方数据库中,以“压电材料,压电催化,活性氧,抗菌,细菌感染,抗感染,耐药性”为中文检索词,以“piezoelectric materials,piezoelectricity,piezoelectric catalysis,piezocatalysis,reactive oxygen species,ROS,bacterial infection,antibacterial strategies,anti-infection,drug resistance,drug-resistant bacteria”为英文检索词。检索时间范围重点为2013年1月至2023年12月,通过阅读文题和摘要进行初步筛选;排除中英文重复性研究及内容不相关的文献,经文献质量评价后,最后纳入68篇文献进行综述。结果与结论:(1)压电材料是一类性质稳定的环境友好型材料,其大多数具有良好的生物相容性。(2)压电材料在压电效应过程中可催化产生大量活性氧,活性氧可通过细胞外氧化和细胞内氧化,破坏细菌的细胞膜、胞内蛋白质、酶以及核酸等物质,影响细菌的结构和功能,甚至导致细菌死亡从而实现抗菌。抗菌性能与催化生成活性氧速率相关,而催化速率与材料体系、形貌及外界条件等多种因素相关。(3)压电催化产生的活性氧对细菌不具备选择性,因此表现出广谱抗菌性,且这种抗菌方式不需要依赖抗菌药物,故不会引起细菌耐药性问题。(4)结合超声波无创、可控性与穿透性强等优点,未来压电材料作为耐药菌感染的辅助或替代治疗等具有重要价值和巨大潜力。(5)目前压电材料催化效率低下的难题限制了其在抗菌领域的应用,如何提高压电催化效率成为了学者们关注的焦点。

Nanotechnology-based delivery systems to overcome drug resistance in cancer

Cancer nanomedicine is defined as the application of nanotechnology and nanomaterials for the formulation of cancer therapeutics that can overcome the impediments and restrictions of traditional chemotherapeutics.Multidrug resistance(MDR)in cancer cells can be defined as a decrease or abrogation in the efficacy of anticancer drugs that have different molecular structures and mechanisms of action and is one of the primary causes of therapeutic failure.There have been successes in the development of cancer nanomedicine to overcome MDR;however,relatively few of these formulations have been approved by the United States Food and Drug Administration for the treatment of cancer.This is primarily due to the paucity of knowledge about nanotechnology and the fundamental biology of cancer cells.Here,we discuss the advances,types of nanomedicines,and the challenges regarding the translation of in vitro to in vivo results and their relevance to effective therapies.

The Com prehensive Evaluation on Four Indices of Drug Re-sistance in Acute Myeloid Leukem ia

To study sensitivity of drug resistance indexes and resistance manner in acute myeloid leukemia (AML), MTT drug sensitivity, growth types of CFU L in vitro , Bcl 2 antigen and Bcl 2/Bax ratio and intracellular fluorescence intensity of daunorubicin (DNR) were determined. In 62 cases of AML, the positive coincidence rate was 73 % with MTT test and the negative coincidence rate was 70 %. In 3 commonly used drugs, if one drug showed sensitivity, the coincidence remission rate reached 71 %. In 51 cases of AML, there were 31 patients in the group of complete remission (CR), in which CFU L of 29 patients showed independent growth. CFU L of 2 patients showed no growth. However, there were 20 patients in the group of non remission (NR), in which CFU L of 14 patients showed independent growth. CFU L of 6 patients showed non growth pattern. Statistical analysis showed significant difference ( P <0.05). In 32 cases of AML, the expression rate of Bcl 2 was 59.55 %±19.56 % in drug sensitive group, and one was 77.36 %±11.91 % in drug resistant group, respectively ( P <0.05). At the same time, the ratio of Bcl 2/Bax was 7.50±5.04 in drug sensitive group and one was 14.32±8.99 in drug resistant group, respectively ( P <0.05). In 15 case of clinically drug resistant AML, the fluorescence histogram of DNR showed left shift of main peak (LSMP) in 12 patients. They were diagnosed as classical drug resistance. Meanwhile, 1 patient showed right shift of main peak (RSMP) in 3 patients. They were diagnosed as re growth drug resistance. It is concluded that MTT and CFU L might be used for prediction of drug sensitivity or resistance when patients were on treatment. Bcl 2 and ratio of Bcl 2/Bax might be associated with the prognosis. DNR histogram could be employed for identify the pattern drug resistance. The strength and weakness of these techniques were discussed.

Study on Antibacterial Effect of Single Chinese Herbs on Staphylococcus aureus

[Objectives] This study was conducted to determine in-vitro antibacterial effect of 58 Chinese herbs on Staphylococcus aureus,and screen single Chinese herbs with better in-vitro antibacterial effect for formulation of prescription. [Methods]Effective components in Chinese herbs were extracted with water,and inhibition zone diameters and minimal inhibitory concentrations of the 58 Chinese herbs against S. aureus were determined by agar plate punching method and micro two-fold method,respectively. [Results] Twenty two kinds of Chinese herbs including Terminalia chebula Retz.,Anemarrhena asphodeloides Bunge.,Prunella vulgaris L,Rheum palmatum L. and Mosla chinensis Maxim. had better antibacterial effect,among which T. chebula Retz.,A. asphodeloides Bunge.,P. vulgaris L,R. palmatum L. and C. sappan Linn showed the best antibacterial effect,with average inhibition zone over 20 mm and MIC lower than 15. 6 mg/ml.[Conclusions]Traditional Chinese herbs have certain antibacterial effect,and this study will provide important theoretical reference for clinical medication and development of prescription.

强制性感染管控措施对维持性血液透析患者血管导管相关感染的影响

目的 分析强制性感染管控措施对维持性血液透析患者发生血管导管相关感染(VCAI)的群体特征、感染率、病原菌及药敏的影响,为临床治疗提供指导。方法 选取2019年3月—2021年2月福建省立医院收治的维持性血液透析患者567例,其中施行强制性管控前(2019年3月—2020年2月)患者295例,施行强制性管控后(2020年3月—2021年2月)患者272例。收集管控前后2组患者的基本信息(包括年龄、性别、置管部位)以及病原学检查结果,对管控前后VCAI群体特征变化、感染率、病原学结果及药敏结果进行比较分析。结果 管控后感染率为10.29%(28/272),低于管控前的16.27%(48/295),差异有统计学意义(χ^(2)=4.356,P=0.037)。管控后患者平均年龄较管控前更高(Z=-6.889,P<0.01)。管控前分离出病原菌58株,以革兰阳性菌为主,占63.79%,管控后分离出病原菌33株,革兰阴性菌为主,占54.55%,管控后革兰阳性菌感染较前有明显下降(χ^(2)=3.899,P=0.048)。管控前检出多重耐药菌28株(48.28%),管控后检出多重耐药菌23株(69.70%)。革兰阳性菌对利奈唑胺、万古霉素敏感;对环丙沙星、克林霉素、红霉素、左氧氟沙星、莫西沙星、苯唑西林耐药率均>50%;青霉素、庆大霉素耐药严重,但分别对粪肠球菌及金黄色葡萄球菌效果突出。革兰阴性菌对厄他培南、亚胺培南、头孢吡肟耐药率较低;青霉素、阿莫西林、头孢唑林、头孢西丁、复方磺胺甲口恶唑耐药率>50%;替加环素对阴性、阳性菌均覆盖良好,且未发现耐药菌。结论 强制性感染管控是行之有效的VCAI防控措施,在目前已形成习惯的基础上可常态化保持。管控后感染人群年龄增大,革兰阳性致病菌检出率下降,多重耐药菌检出率上升,故应加强老年患者的管理,优选颈内静脉作为置管部位并注意抗生素的合理使用。临床推荐利奈唑胺、万古霉素、替加环素作为经验性全身用药,抗生素封管首选万古霉素、头孢吡肟,局部外用可考虑庆大霉素软膏。

贝达喹啉联合背景方案治疗耐药肺结核的疗效

目的:探讨贝达喹啉联合背景方案治疗耐药肺结核的疗效。方法:回顾性选择2022年1月至2023年1月广东省广州市胸科医院收治的159例耐药肺结核患者,按随机对照原则分组。对照组(80例)接受常规背景方案治疗,研究组(79例)在其基础上联合贝达喹啉治疗。于6个月后评估两组病灶吸收率、痰菌转阴率及空洞闭合率,对比两组治疗前后血清肝功能指标、心电图QTc变化,统计两组不良反应发生率。结果:研究组病灶吸收率、痰菌转阴率及空洞闭合率均较对照组高(P<0.05)。两组治疗后丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平升高(P<0.05);研究组治疗后ALT、AST水平与对照组相比,差异无统计学意义(P>0.05)。两组治疗后QTcF值升高,心率降低(P<0.05)。且研究组治疗后QTcF值比对照组高,心率比对照组低(P<0.05)。两组转氨酶升高、白细胞减少及胃肠道反应发生率对比,差异无统计学意义(P>0.05);研究组QT间期延长发生率显著高于对照组(P<0.05)。结论:贝达喹啉联合背景方案治疗耐药肺结核的疗效较佳,未引起肝功能指标异常,但QT间期延长发生率较高。

不同抗生素联合替加环素治疗MDRAB相关VAP患者效果比较

目的探讨不同抗菌药物联合替加环素治疗多重耐药鲍曼不动杆菌(MDRAB)相关呼吸机相关性肺炎(ventilator associated pneumonia,VAP)患者的效果,旨在为临床上更好治疗该病提供方案选择。方法收集2016年1月—2023年8月青岛市市立医院收治的MDRAB相关VAP患者的临床资料,根据治疗方案不同分为替加环素组(A组)56例,头孢哌酮舒巴坦联合治疗组(B组)42例,碳青霉烯类联合治疗组(C组)24例,对三组患者住院期间感染情况及各项疗效指标进行比较。结果三组MDRAB相关VAP感染患者间感染病原体的种类、合并感染部位比较差异均无显著性(P>0.05),B组和C组细菌清除率高于A组(χ^(2)=5.38、4.48,P<0.05),三组患者住院病死率比较差异无显著性(P>0.05)。结论替加环素联合头孢哌酮舒巴坦或碳青酶烯类抗菌药物治疗MDRAB相关VAP的细菌清除率均显著高于单独使用替加环素,联合用药是一种比较好的治疗选择。

耐药肺结核患者血清miR-129-3p、miR-144-3p检测的临床价值

目的探讨血清miR-129-3p和miR-144-3p检测在耐药肺结核中的临床价值。方法收集2021年1月—2022年6月川北医学院附属三台医院行新辅助放化疗的140例耐药肺结核患者(耐药肺结核组),根据治疗6个月的疗效,分为有效组(92例)和无效组(48例);另选取同期与耐药肺结核患者一般资料相匹配的140名体检健康者作为对照组。比较各组血清miR-129-3p、miR-144-3p表达的差异。采用多因素Logistic回归分析评估耐药肺结核患者疗效的影响因素;采用受试者工作特征(ROC)曲线分析治疗2个月后血清miR-129-3p、miR-144-3p水平和白蛋白、白细胞计数预测耐药肺结核患者疗效的效能。结果与对照组比较,耐药肺结核组血清miR-129-3p、miR-144-3p水平显著降低(P<0.05)。治疗2个月,无效组血清miR-129-3p、miR-144-3p水平均显著低于有效组(P<0.05)。血清miR-129-3p、miR-144-3p、白蛋白和白细胞计数是耐药肺结核患者疗效的影响因素(P<0.05)。治疗2个月后血清miR-129-3p、miR-144-3p、白蛋白、白细胞计数联合预测耐药肺结核患者疗效的曲线下面积为0.956,敏感性为87.50%,特异性为92.39%,优于4项指标单独检测(P<0.05)。结论耐药肺结核患者血清miR-129-3p、miR-144-3p水平显著降低。miR-129-3p、miR-144-3p联合白蛋白、白细胞计数对预测耐药肺结核患者疗效有较高的参考价值。

绿原酸抗菌作用及机制的研究进展

绿原酸是植物体在有氧呼吸过程中经莽草酸途径合成的一种苯丙素类物质,自然存在于多种中药材和食物中,杜仲、金银花和咖啡等植物中含量较高,具有抗菌、抗炎、抗氧化、抗癌和免疫调节等多种药理活性。近年来,绿原酸作为研究活性物质的焦点之一,因其抗菌谱广,对多种细菌和真菌均有较好的抗菌活性,故绿原酸对临床菌株的抗菌作用逐渐被重视和研究。本文综述了近年来国内外关于绿原酸对多种致病菌的抗菌作用及机制的研究进展,旨在为绿原酸抗菌作用的深入研究提供参考,为临床抗感染治疗和控制带来新思路,有助于绿原酸在医药领域的开发。

不同耐药结核病检测技术的防控效果和成本效用研究

目的:评估耐药结核的不同检测技术的效果与成本效用。方法:根据耐药结核的发病和传播特征,构建决策树-马尔可夫模型,评估使用固体培养+药物敏感试验、Xpert检测、液体培养+药物敏感试验以及全基因组测序技术进行检测下耐药结核在20年内的发病人数、死亡人数、总医疗成本和健康效益(以质量调整生命年,QALY,来衡量),并进行成本效用分析。结果:与采用固体培养+药物敏感试验的方式相比,Xpert检测表现最佳。在研究周期内,Xpert检测模拟情景下每月平均发病人数、复发人数和死亡人数均低于其他检测技术。此外,成本效用分析显示,与固体培养+药物敏感试验相比,其他3种检测技术均表现出成本效用优势:Xpert检测的增量成本效用比(ICUR)为-2598.89元/质量调整寿命年(QALY),液体培养后药物敏感试验的ICUR为-2476.66元/QALY,全基因组测序(WGS)的ICUR为-2429.46元/QALY。结论:相对于采用固体培养+药物敏感试验的方式,采用Xpert检测、液体培养+药敏试验和全基因组测序技术来检测耐药结核均可以降低耐药结核的发病人数、死亡人数和复发人数,并提高健康效用。其中,Xpert检测具有最佳的成本效用。

天然植物薰衣草精油对多重耐药鲍曼不动杆菌的抗菌作用及机制研究

目的探讨天然植物薰衣草精油对多重耐药鲍曼不动杆菌的抗菌作用及初步机制。方法用微量稀释法测定薰衣草精油对多重耐药鲍曼不动杆菌的最低抑菌浓度和最低杀菌浓度;用杀菌动力学研究进一步确定其起效和维持时间;用小鼠感染模型评价薰衣草精油对创口愈合的促进作用;用结晶紫染色定量测定法对其生物膜的抑制和清除作用进行研究;用激光共聚焦显微镜观察生物膜中细菌存活情况;用核酸蛋白测定仪器检测3 mg/mL、6 mg/mL薰衣草精油干预后的细菌DNA核酸和蛋白质泄漏量;用钾离子试剂盒测定钾离子泄漏量,并采用蛋白组学技术结合生物信息学研究方法,初步探究薰衣草精油抗多重耐药鲍曼不动杆菌的作用机制。结果薰衣草精油的最低抑菌浓度和最低杀菌浓度均为6 mg/mL,在120 min时,该浓度可杀死几乎所有多重耐药鲍曼不动杆菌,且呈现明显的剂量依赖效应和时间依赖效应。整体动物模型评价表明,3 mg/mL和6 mg/mL薰衣草精油均能促进创口愈合,疗效明显。进一步研究发现,3 mg/mL薰衣草精油具有一定的多重耐药鲍曼不动杆菌生物膜抑制作用,且能显著增加DNA核酸和蛋白质的泄漏量,并能促进钾离子外流。同时,6 mg/mL薰衣草精油展现了对多重耐药鲍曼不动杆菌生物膜的清除作用。蛋白组学研究提示,薰衣草精油的抗菌作用可能与影响多重耐药鲍曼不动杆菌的氧化还原酶活性和细胞代谢过程,干扰细胞壁/膜/包膜等结构的生物合成有关。结论薰衣草精油在3 mg/mL时即可发挥对多重耐药鲍曼不动杆菌的抗菌作用,其作用机制可能与破坏细菌生物膜和干扰细菌代谢有关。

加减葛根芩连汤对感染耐药性大肠杆菌雏鸡的治疗效果

为了评价加减葛根芩连汤对感染耐药性大肠杆菌雏鸡的治疗效果,本试验首先用耐药性大肠杆菌感染4日龄雏鸡,6 h后分别灌服低(0.125 mL/羽)、中(0.25 mL/羽)和高(0.5 mL/羽)剂量的加减葛根芩连汤、锦心口服液(中药对照组)、恩诺沙星(西药对照组)和生理盐水(感染对照组和空白对照组),连续灌服5 d,计算各组雏鸡存活率和治愈率、采食量和饮水量、体重及其增量,分析血液生理生化指标和免疫器官指数。结果显示,低、中和高剂量组雏鸡24 h存活率分别为85%、80%和65%,极显著高于中药对照组(50%)和西药对照组(50%)(P<0.01);中和高剂量组雏鸡7d存活率和治愈率均达70%,极显著高于感染对照组和西药对照组(P<0.01);各感染组雏鸡每日平均采食量和平均饮水量在感染后明显减少,用药后均恢复并趋于稳定,体重保持稳定增长。血液生理生化指标结果显示,低、中和高剂量组白细胞数目显著低于西药对照组(P<0.05),平均血红蛋白含量显著高于空白对照组(P<0.01、P<0.001、P<0.01),中和高剂量组平均红细胞血红蛋白浓度显著低于空白对照组(P<0.05),高剂量组红细胞分布宽度变异系数显著高于其他各组(P<0.05),低、中和高剂量组肌酐含量极显著低于西药对照组(P<0.01)。免疫器官指数结果显示,低和中剂量组感染雏鸡法氏囊和脾脏指数极显著高于西药对照组(P<0.01),高剂量组胸腺指数显著高于中药对照组(P<0.05)。结果表明,不同剂量的加减葛根芩连汤对耐药性大肠杆菌感染雏鸡均具有较好的治疗效果,且中和高剂量的治疗效果显著优于低剂量,具有替代抗生素的潜力,可为耐药性大肠杆菌病的防治提供理论支撑。

去甲泽拉木醛的体外抗真菌作用研究

目的 研究去甲泽拉木醛的体外抗真菌作用。方法 采用微量液基稀释法测定去甲泽拉木醛与氟康唑单独应用于23株真菌的最低抑菌浓度(MIC),以棋盘式微量液基稀释法测定两药联合抗耐药白念珠菌的协同指数(FICI),判断两药联合抗菌效果;并通过纸片扩散实验直观验证两药联合的协同作用。最后通过CCK-8法测定去甲泽拉木醛的细胞毒性。结果 去甲泽拉木醛单用时呈现广谱的抗真菌作用,MIC范围为4~32 g/L。两药联用时,可将氟康唑的有效浓度从大于64 g/L降至0.25 g/L,FICI值介于0.129~0.254之间,两药表现出协同抗耐药白念珠菌作用。CCK-8结果显示,去甲泽拉木醛在高于MIC值4倍浓度下才展示出细胞毒性。结论 去甲泽拉木醛表现出较好的抗真菌作用,与氟康唑联合时有很好的协同效果,且毒性较低。

头孢地尔对产金属β-内酰胺酶革兰阴性菌的作用现状研究

产金属β-内酰胺酶(MBLs)革兰阴性菌是临床常见的感染病原菌,该类菌可引起多种严重感染,其中产金属β-内酰胺酶肺炎克雷伯菌(KP)是世界范围内的重要医院获得性感染菌,对当前抗感染治疗构成严重威胁。头孢地尔作为新型头孢菌素,具有抗菌活性强、作用范围广、组织穿透力强等特点,对产碳青霉烯酶的肠杆菌、鲍曼不动杆菌、铜绿假单胞菌、嗜麦芽窄单胞菌有强大的抗菌活性,其中它对金属β-内酰胺酶也有相当好的活性。本研究针对头孢地尔对产金属β-内酰胺酶革兰阴性菌的作用进行了全面的现况分析研究。