Analysis of Multi-Drug Resistant Organism Surveillance and Antimicrobial Resistance Early Warning in a Hospital in 2022

Objective:To determine the clinical distribution of multi-drug resistant organism(MDRO)in Jiangyan Hospital and the monitoring and warning of drug-resistance bacteria to provide an important basis for guiding the application of broad-spectrum antibiotics in clinical treatment and reducing the occurrence of nosocomial infection.Methods:Retrospective screening and analysis were conducted on the pathogenic strains of hospitalized patients in our hospital in 2022.Results:A total of 2,769 strains of pathogenic bacteria and 390 strains of MDRO were detected and isolated in our hospital in 2022;the detection rate of MDRO was 14.08%.A total of 516 strains(18.64%)Klebsiella pneumoniae(KP)and 62 strains(12.02%)of carbapenem-resistant Klebsiella pneumoniae(CR-KP)were detected;436 strains(15.75%)of Escherichia coli(ECO)were detected,including 8 strains(1.83%)of CR-ECO;342 strains(12.35%)of Pseudomonas aeruginosa(PA)and 116 strains(33.92%)of CR-PA were detected;there were 194 strains(7.01%)of Acinetobacter baumannii(AB),among which 125 strains(64.43%)were CR-AB;there were 291 strains(10.51%)of Staphylococcus aureus,among which 79 strains(27.15%)of methicillin-resistant Staphylococcus aureus(MRSA)were detected;78 strains(2.82%)of Enterococcus faecalis were detected,and vancomycin-resistant enterococcus(VRE)was not detected.The first five MDROs were CR-AB,CR-PA,MRSA,CR-KP,and CR-ECO.The top five departments with the highest MDRO detection rate in 2022 were the ICU(37.44%),the Pulmonology Department(ward 13;31.03%),the Department of Rehabilitation(ward 5;6.67%),the Department of Neurosurgery(ward 11;4.62%),and the Department of General Surgery(ward 10;3.59 The resistance rate of antibacterial drugs is divided into four levels for early warning:30%to 40%,41%to 50%,51%to 75%,and 75%or more.Conclusion:Our hospital should strengthen the monitoring of antimicrobial resistance warning related to MDRO and the abuse of antimicrobial drugs.Based on the results of drug sensitivity and antimicrobial resistance warning,the use of antibiotics should be standardized in clinical practice to reduce nosocomial infection。

Reversing multidrug resistance by tyrosine kinase inhibitors

Recently,a large number of tyrosine kinase inhibitors(TKIs) have been developed as anticancer agents.These TKIs can specifically and selectively inhibit tumor cell growth and metastasis by targeting various tyrosine kinases and thereby interfering with cellular signaling pathways.The therapeutic potential of TKIs has been hindered by multidrug resistance(MDR),which is commonly caused by overexpression of ATP-binding cassette(ABC) membrane transporters.Interestingly,some TKIs have also been found to reverse MDR by directly inhibiting the function of ABC transporters and enhancing the efficacy of conventional chemotherapeutic drugs.In this review,we discuss ABC transporter-mediated MDR to TKIs and MDR reversal by TKIs.

Reversing effects of interferon α on drug resistance of bone marrow cells in leukemia

Objective:To investigate the reversing effects of interferon a (IFN-a) on drug resistance of bone marrow cells in leukemia and its possible mechanism. Methods: Before and after the bone marrow cells extracted from50 cases of acute leukemia and 2 of chronic leukemia (BP) were incubated in the media with the addition of IFN-α,MDR1 mRNA expression and concentration of daunorubicin (DNR) in the cells were determined respectively withSAG-ISH and respectrofluorimetry. Results: Twenty-four (64. 2% ) our of all the 52 cases presented MDR1 mRNA expression. There was significant difference in the concentration of DNR between MDR1-positive and MDR1-negative cases before and after incubation. In all the 52 cases, no significant difference was found between the concentration of DNR before the incubation and that after the incubation. Conclusion: IFN-a can increase the concentration of DNR in the bone marrow cells in leukemia. No occurrence of MDR reversal is on the level of MDRl buton other levels.

Reversal of Multi-Drug Resistance by Vector-Based-ShRNA-Mdr1 In Vitro and In Vivo

In order to investigate the effects of vector-based hairpin small interference RNA （shRNA） on the reversal of multi-drug resistance （mdr） of A2780/Taxol cells, a novel vector pEGFP-HI/mdrl containing mdrl-shRNA targeting at position 2943-2963 of mdrl was designed and synthesized. Subsequently, A2780/Taxol cells were transfected with pEGFP-H1/rndrl, and the expression ofmdrl mRNA and P-gp was detected by using RT-PCR and Western blot respectively. MTT was used to measure the 50% inhibition concentration （IC50） of Taxol to A2780/Taxol cells. The results showed that at the 24th and 48th h after transfection, the expression of mdrl mRNA was decreased to （52.1±1.0）% and （0.01±1.7）%, and that of P-gp decreased to （88.3±2.1）% and 0%, respectively. At the 48th h after transfection, the relative reversal rate of A2780/Taxol cells to Taxol was 69.54%. In vivo, the nude mice xenografts were injected with pEGFP-H1/mdrl, and then administrated Taxol. The tumor volume in pEGFP-H1/mdrl-transfected group was significantly reduced as compared with that in blank control group or pEGFP-Hl-transfected group （807.20±103.16 vs 1563.78±210.54 or 1480.78±241.24 mm^3, both P〈0.01）. These results suggested that transfection of pEGFP-HI/mdrl could efficiently down-regulate the expression of mdrl mRNA and P-gp in A2780/Taxol cells, and effectively restore the sensitivity of A2780/Taxol ceils to Taxol both in vitro and in vivo.

Clinical study of Cangbai Shiduqing Granul in reversing drug resistance of ureaplasma urealyticum

Ureaplasma Urealyticum(UU) can not only cause a wide range of nongonococcalinfectionsto urogenital tract,but also lead to infertility,sterility,intrauterinefetal infection,abortion or other bad consequences.For males,UU may cause prostatitis,epididymitis and other diseases.With great harm to the human health,UU infection has been taken as one of the most important STDs in China for prevention and cure.However,the drug resistance of UU is increasingly stronger with the widespread use of antibiotics.Many nongonococcal patients with mycoplasma infection often fail to be cured after a long time of treatment,and drug sensitive tests find that,multidrug resistance brings physical and mental pains to patients all the time.Luckily,integrated Chinese traditional and western medicine greatly improves the cure rate,though the mechanism is not clear.There have been many studies on the reversion action and mechanism of TCM on the antibiotic resistance of bacteria,but studies on the reversion to UU drug resistance are deficient.Here we chose some voluntary patients with multidrug resistance as the research objects,who received treatment in my hospital in recent 3 years.They were given the oral administration of self-prescribed Cangbai Shiduqing Granule.Then,Cangbai Shiduqing Granule's reversion effect on UU drug resistance,namely,the sensitivity transformation situation of drug-resistant antibiotics,was observed.And the observation results are presented in the paper.

Reversal of multidrug resistance of hepatocellular carcinoma cells by metformin through inhibiting NF-κB gene transcription

AIM: To interfere with the activation of nuclear factor-κB(NF-κB) with metformin and explore its effect in reversing multidrug resistance(MDR) of hepatocellular carcinoma(HCC) cells.METHODS: Expression of P-glycoprotein(P-gp) and NF-κB in human HepG 2 or HepG 2/adriamycin(ADM) cells treated with pC MV-NF-κB-small interference RNA(siR NA) with or without metformin, was analyzed by Western blot or fluorescence quantitative PCR. Cell viability was tested by CCK-8 assay. Cell cycle and apoptosis were measured by flow cytometry and Annexin-V-PE/7-AnnexinV apoptosis detection double staining assay, respectively. RESULTS: P-gp overexpression in HepG 2 and HepG 2/ADM cells was closely related to mdr1 mR NA(3.310 ± 0.154) and NF-κB mR NA(2.580 ± 0.040) expression. NF-κB gene transcription was inhibited by specific siR NA with significant down-regulation of P-gp and enhanced HCC cell chemosensitivity to doxorubicin. After pretreatment with metformin, Hep G2/ADM cells were sensitized to doxorubicin and P-gp was decreased through the NF-κB signaling pathway. The synergistic effect of metformin and NF-κB siR NA were found in HepG 2/ADM cells with regard to proliferation inhibition, cell cycle arrest and inducing cell apoptosis. CONCLUSION: Metformin via silencing NF-κB signaling could effectively reverse MDR of HCC cells by downregulating MDR1/P-gp expression.

The Roles of Four Multi-drug Resistance Proteins in Hepatocellular Carcinoma Multidrug Resistance

The roles of multi-drug resistance protein 1 （MDR1）, multi-drug resistance related protein 1 （MRP1）, lung resistance protein （LRP） and breast cancer resistance protein （BCRP） in the multi-drug resistance （MDR） of hepatocellular carcinoma （HCC） were studied. By exposing HepG2 cell line to progressively increased concentrations of adriamycin （ADM）, HepG2 multi-drug resistant subline （HepG2/ADM） was induced. The MDR index of HepG2/ADM was detected by using MTT. The expressions of the four MDR proteins in the three cell lines （L02, HepG2, HepG2/ADM） were investigated at mRNA and protein levels by real-time RT-PCR and Western blot respectively. Our results showed that when the ADM concentration was under 100 pg/L, HepG2 could easily be induced to be drug-resistant. The IC50 of the HepG2/ADM to ADM was 282 times that of HepG2. The expression of MDR1 and BCRP mRNA in HepG2/ADM cells were 400 and 9 times that of HepG2 cells respectively while there was no difference in the mRNA expressions of MRPl and LRE There was no difference between HepG2 and L02 cells in the mRNA expressions of the four genes. At the protein level, the expressions of MDRI, BCRP and LRP but MRPl in HepG2/ADM were significantly higher than those of HepG2 and L02. Between HepG2 and L02, there was no difference in the expressions of four genes at the protein level. HepG2/ADM is a good model for the study of MDR. The four genes are probably the normally expressed gene in liver. The expressions of MDRl and BCRP could be up-regulated by anti-cancer agents in vitro. The MDR of HCC was mainly due to the up-regulation of MDR1 and BCRP but MRP1 and LRE These findings suggest they may serve as targets for the reversal of MDR of HCC.

β-escin reverses multidrug resistance through inhibition of the GSK3β/β-catenin pathway in cholangiocarcinoma

AIM: To develop a safe and effective agent for cholangiocarcinoma(CCA) chemotherapy. METHODS: A drug combination experiment was conducted to determine the effects of β-escin in c o m b i n a t i o n w i t h c h e m o t h e ra p y o n C C A c e l l s. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay was performed to determine the effects of β-escin and common chemotherapeutics on the proliferation of human CCA cells(QBC939, Sk-Ch A-1, and MZ-Ch A-1). Immunocytochemistry was used to detect the expression of P-glycoprotein(P-gp) protein. Luciferase reporter assay was used to detect the activation of the Wnt/β-catenin pathway. The protein levels of P-gp, p S9-GSK3β, p T216-GSK3β, GSK3β, β-catenin, and p-β-catenin were further confirmed by western blotting.RESULTS: The drug sensitivity of QBC939 and QBC939/5-fluorouracil(5-FU) cells to 5-FU, vincristine sulfate(VCR), or mitomycin C was significantly enhanced by β-escin compared with either agent alone(P < 0.05). In addition, the combination of β-escin(20 μmol/L) with 5-FU and VCR was synergic with a combination index < 1. Further investigation found that the m RNA and protein expression of P-gp was downregulated by β-escin. Moreover, β-escin induced GSK3β phosphorylation at Tyr-216 and dephosphorylation at Ser-9, resulting in phosphorylation and degradation of β-catenin. Interestingly, activation of the GSK3β/β-catenin pathway induced by Wnt3 a resulted in upregulation of P-gp, which was effectively abolished by β-escin, indicating that β-escin down-regulated P-gp expression in a GSK3β-dependent manner.CONCLUSION: β-escin was a potent reverser of P-gpdependent multidrug resistance, with said effect likely being achieved via inhibition of the GSK3β/β-catenin pathway and thus suggesting a promising strategy of developing combination drugs for CCA.

Relationship between Methylation Status of Multi-drug Resistance Protein(MRP) and Multi-drug Resistance in Lung Cancer Cell Lines

Objective： To study the relationship between the methylation status of multi-drug resistance protein （MRP） gene and the expression of its mRNA and protein in lung cancer cell lines. Methods： Human embryo lung cell line WI-38, lung adenocarcinoma cell line SPCA-1 and its drug-resistant cells induced by different concentrations of doxorubicin were treated with restriction endonuclease Eco47III. The methylation status of MRP was examined by PCR, and the expressions of its mRNA and protein were evaluated by in situ hybridization and immunohistochemistry. Results： MRP gene promoter region of WI-38 cells was in hypermethylation status, but the promoter region of MRP in SPCA-1 cells and their resistant derivatives induced by different concentrations of doxorubicin were in hypomethylation status. There were significant differences in the expression of MRP mRNA among WI-38 cell line, SPCA-1 cells and their drug-resistant derivatives induced by different concentration of doxorubicin. Consistently, MRP immunostaining presented similar significant differences. Conclusion： The promoter region of MRP in SPCA-1 lung adenocarcinoma cells was in hypomethylation status. The hypomethylation status of 5＇ regulatory region of MRP promoter is an important structural basis that can increase the activity of transcription and results in the development of drug resistance in lung cancer.

Effect of Rare Earth on Microstructure and Corrosion Resistance of Pulse Reversal Current Electrodeposition Ni-Co Alloy Coatings

The effect of adding RE to plating bath on microstructure and corrosion resistance of Ni-Co alloy coatings prepared by pulse reversal current electrodeposition was studied by means of SEM/EDS, electrochemical analysis and corrosion mass loss etc. The results show that adding proper RE to plating solution can promote the microstructure of coatings compacter, the surface smoother and the crystal finer, and improve the corrosion resistance. The coatings exhibite the highest corrosion resistance when the concentration of RE reaches 0.25 g·L -1. The reason of increasing corrosion resistance by adding RE was also investigated.

Reversal of HCC Drug Resistance by Using Hammerhead Ribozymes against Multidrug Resistance 1 Gene

To reverse multidrug resistance（MDR） of HepG2 by anti-MDR1 hammerhead ribozyme, an anti-MDR1 hammerhead ribozyme was developed and delivered to P-gp-overproducing human hepatocarcinoma cell line HepG2 by a retroviral vector containing RNA polymerase Ⅲ promoter. The expression of mdrl/Pgp and Rz was detected in HepG2, HepG2 muhidrug-resistant cell line and HepG2 Rz-transfected cells by semi-quantitative RT-PCR and Western blot methods. Moreover, MTT assay was employed to detect the sensitivity of these ribozyme-transfected cells, and Rhodamine123 （Rh123） was used to test the function of Pgp. The Rz- transfected HepG2 cells became doxorubicin-sensitive, which was concomitant with the decreased MDR1 expression. The study showed that the retrovirus vector encoding the anti-MDR1 ribozyme may be applicable to the treatment of MDR cells.

Direct and Residual Microbicidal Efficacy of Various Antiseptics against Multi-Drug Resistant Bacteria

Background: Infections in ICU’s patients are known to often originate from the colonization of wounds by the patient’s endogenous microbiota, and to eventually lead to secondary sepsis. Aim: to compare in vitro the direct and residual effects after different exposure times of 4% chlorhexidine, and of 0.1% and 0.04% polyhexanide (in gel and solution forms), on ATCC-microorganisms, and too, on bacterial strains obtained from ICU patients. Methods: We used wild multi-drug resistant strains recently obtained from the wounds of patients hospitalized at ICU and reference strains from the American Type Culture Collection (ATCC). Chlorhexidine 4% was studied as a reference solution. The direct and residual effects of the 0.1% and 0.04% polyhexanide, in gel and solution forms, were analyzed using cotton germ carriers. To evaluate the direct effect, we exposed the strains to the antiseptic. To assess the residual effect, the germ-carriers were impregnated with antiseptic and were allowed to dry before we contaminated them. We inoculated the germ carriers in a culture medium with an inhibitor of antiseptic effect to count the number of surviving microorganisms. Findings: 0.1% Polyhexanide solution proved a direct and residual efficacy after 24 hours equivalent to 4% chlorhexidine. Is very important to highlight that this great efficacy did not change according to whether they were ATCC or multidrug-resistant strains. Conclusions: 0.1% polyhexanide demonstrated a great direct and residual efficacy (like 4% chlorhexidine), against multi-drug resistant strains isolated from ICU’s patients. Moreover, due to its few cytotoxicity against keratinocytes and fibroblasts can be an optimal antiseptic for burns, wounds or ulcers.

Molecular characterization of antimicrobial multi-drug resistance in non-typhoidal Salmonellae from chicken and clam in Mangalore, India

Salmonella enterica has been documented as one of the leading causes of salmonellosis throughout the world and is most commonly associated with the consumption of contaminated food products. Thus, this research was aimed at studying the antimicrobial susceptibility pattern and detection of quinolone resistance in Salmonella spp isolated from food of animal origin. Thirty-six Salmonella isolates comprising 8 from poultry and 28 from seafood（clams） were identified, serotyped and characterized for their antimicrobial susceptibility against 10 different antibiotics. Plasmid DNA was isolated from all the isolates by alkaline lysis, quinolone resistant non-typhoidal S. Weltevreden were examined for mutation in the DNA gyrase coding gene. Among the 36 Salmonella isolates, 20 were S. weltevreden（8 from poultry and 12 from seafood） and 16 were S. Typhimurium（from seafood）. All the isolates showed multiple resistance to nalidixic acid, tetracycline, co-trimoxazole and nitrofurantoin, but, interestingly, the isolates were 100% susceptible to ampicillin, chloramphenicol and gentamicin. Resistant isolates from the study carried the genes responsible for resistance to respective antibiotics. The strain S130 isolated in the study showed single point mutation,Asp87Gly, at position 87 in quinolone resistance determining region. It revealed mutation in quinolone resistance determining region as a cause for quinolone resistance in non-typhoidal Salmonellae. The occurrence of genes accountable for plasmid mediated resistance to quinolones（viz., qnrA, qnrB and qnrS） in plasmid of non-typhoidal Salmonellae isolates provides evidence for plasmid mediated quinolone resistance.

Multi-Drug Resistance Pattern of Lactose Non-Fermenting <i>Escherichia coli</i>as Causative Agent of Urine Tract Infections in Luanda, Angola

This prospective study was carried out to assess the sensitivity and resistance pattern of lactose non-fermenting Escherichia coli from July 2018 to December 2018 in the Laboratory of Microbiology at Luanda Medical Center, Angola. Out of 1170 patient, a total of 120 urine specimens infected with Escherichia coli (>105 CFU/ml) were collected according to the routine protocol of urinalysis. Among these 120 isolates, 25 (21%) isolates were determined as “atypical”, lactose non-fermenting E. colis trains. The twenty-five lactose non-fermenting Escherichia coli strains isolated from urine samples in Luanda Medical Center were declared as Multiple Drugs-Resistant strains with high resistance to Cefalexine (100%), Cefuroxime (100%), Ceftriaxone (92%), Gentamycin (92%), Ciprofloxacin (72%) and Amoxiciclin/Clavulanic (80%). The alarming resistance level to the first-choice drugs for the treatment of urinary tract infections caused by non-fermentative lactose E. coli was observed.

Reversal of multidrug resistance in vincristine-resistant human gastric cancer cell line SGC7901/VCR by LY980503

瞄准：调查 LY980503 的颠倒效果， benflumetol 衍生物，在上多在长春新碱(VCR ) 的药抵抗抵抗的人的胃的癌房间线 SGC7901/VCR。方法：一根人的胃的癌症房间线， SGC7901，和它的 VCR- 抵抗变体的房间， SGC7901/VCR，与 LY980503 和 /or doxorubicin (纪录影片) 被栽培。药在试管内的细胞毒性是由 MTT 方法的 assayed。基于流动 cytometric 技术，纪录影片的举起被测量联系纪录影片的吝啬的荧光紧张(MFI ) 在这些房间检测。结果：SGC7901/VCR 房间是对与 SGC7901 房间比较的纪录影片更抵抗的 23.5 次。在 2.0 mumol/L -10 mumol/L 的集中的 LY980503 没有明显的细胞毒性到 SGC7901 和 SGC7901/VCR 房间。在有在 2.0 ， 4.0 和 10 mumol/L 的集中的 LY980503 的同时的治疗以后，到 SGC7901/VCR 房间的纪录影片的 IC50 从 1.6 +/-减少了 0.12 mumol/L 到 0.55 +/- 0.024 ， 0.25 +/- 0.032 和 0.11 +/- 0.015 mumol/L ，分别地这样，由2.9褶层增加 DOX 敏感( P 【 0 。05 ) ， 6.4 褶层(P 【 0。01 ) 并且 14.5 褶层(P 【 0。01 ) 分别地。在纪录影片的举起学习，有 LY980503 的 SGC7901/VCR 房间的同时的孵化显著地增加了 DOX 在 SGC7901/VCR 房间的联系 MFI。没有如此的结果在父母 SGC7901 房间被发现。结论：在非细胞毒素的集中的 LY980503 能有效地由增加细胞内部的纪录影片累积围绕 SGC7901/VCR 房间的抵抗到纪录影片。

Multidrug Resistance P-glycoprotein Function of Bone Marrow Hematopoietic Cells and the ReversalAgent Effect

The multidrug resistance P-glycoprotein (P-gp) expression and func-tion in hematopoietic stem/progenitor cells were studied to investigate whether the inhibition of hematopoietic cell P-gp function by multidrug resistance reversal agent increases the cytotoxicity of chemotherapy drugs on the hematopoietic cells.The expression of P-gp on the surface of CD cells from healthy human marrow was examined by flow cytometry. The multidrug resistance reversal agent MS-209 was used to measure the effects of MS-209 on the Rhodamin-123 uptaking o fCD hematopoietic cells. By using methylcellulose semi-solid culture, normal human granulocyte-macrophage clonal formation unit (CFU-GM) was cultured. The changes in CFU-GM inhibitory rate caused by daunorubicin were determined in the presence or absence of MS-2O9. The results showed that the P-gp expression rate of bone marrow CDL cells was 13. 3 %. MS-209 obviously increased the Rhodamin-123 uptake of CD positive cells. The mean inhibitory rate of daunorubicin for CFU-GM was 29. 6 %, but it was increased to 43. 3 % in the presence of MS-209 with the difference being significant (P< 0. 05). It was concluded that hematopoietic cells expressed P-gp protein and possessed active function- MS-209could inhibit the membrane efflux pump and increase the cytotoxicity of chemotherapy drugs to the clonal growth of hematopoeitic stem cells, suggesting the side effects of these drugs on the hematopoietic system should be taken into consideration in the clinical use.

Reversion of Multidrug-Resistance by Proteasome Inhibitor Bortezomib in K562/DNR Cell Line

Objective：To observe the reversion of multi-drug resistance by proteasome inhibitor bortezomib in K562/DNR cell line and to analyze the possible mechanism of reversion of multidrug-resistance.Methods：MTT method was used to determine the drug resistance of K562/DNR cells and the cellular toxicity of bortezomib.K562/DNR cells were cultured for 12 hours,24 hours and 36 hours with 100 μg/ml DNR only or plus 4 μg/L bortezomib.The expressions of NF-κB,IκB and P-gp of K562/DNR were detected with Western blot method,the activity of NF-κB was tested by ELISA method and the apoptosis rate was observed in each group respectively.Results：The IC50 of DNR on cells of K562/S and K562/DNR groups were 1.16 μg/ml and 50.43 μg/mL,respectively.The drug-resistant fold was 43.47.The IC10 of PS-341 on Cell strain K562/DNR was 4 μg/L.Therefore,4 μg/L was selected as the concentration for PS-341 to reverse drug-resistance in this study.DNR induced down-regulation of IκB expression,up-regulation of NF-κB and P-gp expression.After treatment with PS-341,a proteasome inhibitor,the IκB degradation was inhibited,IκB expression increased,NF-κB and P-gp expression decreased in a time dependent manner.Compared to DNR group,the NF-κB p65 activity of DNR＋PS-341 group was decreased.Compared to corresponding DNR group,DNR induced apoptosis rate increases after addition of PS-341 in a time dependent manner.Conclusion：Proteasome inhibitor bortezomib can convert the leukemia cell drug resistance.The mechanism may be that bortezomib decreases the degradation of IκB and the expression of NF-κB and P-gp,therefore induces the apoptosis of multi-drug resistant cells.

Cancerous multi-drug resistance is reduced by Leptomycin B treatment in CCRF-CEM/Taxol cellsCancerous multi-drug resistance is reduced by Leptomycin B treatment in CCRF-CEM/Taxol cells

Objectives: Multi-drug resistance (MDR) to chemotherapy remains a major obstacle to overcome in the successful treatment of patients with cancers. It was recently discovered that Leptomycin B (LMB) reduces the paclitaxel-induced MDR in CCRF-CEM/Taxol cells. However, the mechanism remains unclear. Here we sought to explore the mechanism of LMB to reduce the MDR induced by paclitaxel. Results: LMB has remarkable cytotoxic effects in both sensitive CCRF-CEM and resistant CCRF-CEM/Taxol cell lines. The paclitaxel-induced MDR was reduced by 0.013 μm of LMB. Lower concentration of LMB regulated cell cycle progress, in situ expressions of P-gp, MRP1, and LRP, expression of CRM1, and localization of P-gp and CRM1 in CCRF-CEM/taxol cells. Study Design: Cytotoxicity of LMB on cancerous cell lines was determined by MTT assay. Cell cycle progress and in situ expressions of P-gp, MRP1, and LRP were analyzed by flow cytometry. Expression of CRM1 in the cells was examined by Western blot. And co-localization between P-gp and CRM1 was determined by laser confocal microscopy. Conclusion: The paclitaxel-induced MDR of CCRFCEM/Taxol cells was reduced by lower concentration of LMB. The mechanisms might be related to decreasing in situ expression of drug transporter proteins, promoting cell cycle progress, and altering co-localization between P-gp and CRM1 in the resistant cells.

Sign reversal of anisotropic magnetoresistance and anomalous thickness-dependent resistivity in Sr_(2)CrWO_(6)/SrTiO_(3) films

High-quality Sr_(2)CrWO_(6)(SCWO) films have been grown on SrTiO_(3)(STO) substrate by pulsed laser deposition under low oxygen pressure. With decrease of the film thickness, a drastic conductivity increase is observed. The Hall measurements show that the thicker the film, the lower the carrier density. An extrinsic mechanism of charge doping due to the dominance of oxygen vacancies at SCWO/STO interfaces is proposed. The distribution and gradient of carrier concentration in SCWO films are considered to be related to this phenomenon. Resistivity behavior observed in these films is found to follow the variable range hopping model. It is revealed that with increase of the film thickness, the extent of disorder in the lattice increases, which gives a clear evidence of disorder-induced localization charge carriers in these films.Magnetoresistance measurements show that there is a negative magnetoresistance in SCWO films, which is considered to be caused by the magnetic scattering of magnetic elements Cr^(3+) and W^(5+). In addition, a sign reversal of anisotropic magnetoresistance(AMR) in SCWO film is observed for the first time, when the temperature varies across a characteristic value, T_(M). Magnetization-temperature measurements demonstrate that this AMR sign reversal is caused by the direction transition of easy axis of magnetization from the in-plane ferromagnetic order at T > T_(M) to the out-of-plane at T < T_(M).

Main coolant pump resistance influence on single phase water reverse flow in the inverted U-tubes under natural circulation

Based on nuclear power plant(NPP) best-estimate transient analysis with RELAP5 / MOD3 code,the reactor point kinetics model in RELAP5 / MOD3 code is replaced by the two-group,3-D space and time dependent neutron kinetic model,and two-fluid model is replaced by drift flux model.A coupled three-dimensional physics and thermal-hydrodynamics model is used to develop its corresponding computing code,thus simulating natural circulation of single-phase flow for the PWR.In this paper,we report the forward and reverse flow distribution in the inverted U-tubes of the steam generator(SG) under some typical operating conditions in the natural circulation case, and analyze the influence of main coolant pump resistance on the forward and reverse flow distribution.The calculation results show that,the pressure drop between SG inlet and outlet plenum decreases,and the SG inlet and outlet mass flow decrease with an increased main coolant pump resistance,but net mass flux of reverse flow in inverted U-tubes,and the ratio of mass flow in all reverse flow tubes to that of main coolant pipeline increase, meanwhile,the secondary steam load is invariable in this process.