Nosocomial spontaneous bacterial peritonitis antibiotic treatment in the era of multi-drug resistance pathogens: A systematic review

To systematically review literature upon aetiology of nosocomial spontaneous bacterial peritonitis (N-SBP) given the rising importance of multidrug-resistant (MDR) bacteria. METHODSA literature search was performed on MEDLINE and Google Scholar databases from 2000 to 15th of November 2016, using the following search strategy: “spontaneous” AND “peritonitis”. RESULTSThe initial search through electronic databases retrieved 2556 records. After removing duplicates, 1958 records remained. One thousand seven hundred and thirty-five of them were excluded on the basis of the screening of titles and abstract, and the ensuing number of remaining articles was 223. Of these records, after careful evaluation, only 9 were included in the qualitative analysis. The overall proportion of MDR bacteria turned out to be from 22% to 73% of cases across the studies. CONCLUSIONN-SBP is caused, in a remarkable proportion, by MDR pathogens. This should prompt a careful re-assessment of guidelines addressing the treatment of this clinical entity.

Multi Drug Resistance Bacterial Isolates of Surgical Site Infection

Multi drug resistance microorganism is considered to be one of the major health problems. The aim of this study was to determine antibiotic susceptibility pattern of bacterial pathogens of surgical site infection. A total 250 samples were included, out of which 62.4% showed significant bacterial growth. Gram negative bacteria were 85.25% and gram positive bacteria were 14.75%;among them 65.38% of the total isolates were multi drug resistance (MDR). The age group between 31 - 40 found the highest number of isolates 22.4%. Among gram negative bacilli, the highest production of MDR was found in Acinetobacter spp. followed by Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli. In gram positive cocci, the highest production of MDR was found in Staphylococcus aureus. Acinetobacter spp. was found highly susceptible to amikacin and gentamycin 20.1% followed by ofloxacin and ciprofloxacin 18.6% and 16.2% respectively. Staphylococcus aureus showed 100% sensitive to clindamycin whereas penicillin showed 100% resistance followed by amoxycillin (93.75%). Amikacine and clindamycin were drugs of choice for gram negative and gram positive bacteria respectively. This study showed that alarming increase of infections was caused by multi drug resistance bacterial organisms. It increases length of stay and may produce lasting sequelae and requires extra resources for investigations, management and nursing care. Surveillance of surgical site infection is a useful tool to demonstrate the magnitude of the problem and find out appropriate preventive methods.

Multiple drug resistance and bacterial infection

Drug resistance is becoming a great problem in developing countries due to excessive use and misuse of antibiotics. The emergence of new pathogenic strains with resistance developed against most of the antibiotics which may cause,difficult to treat infection.To understand the current scenario in different mode of infection is most important for the clinicians and medical practitioners.This article summarized some common infections and antibiotic resistance pattern found among these pathogens.

Drug resistance mechanisms in cancers:Execution of prosurvival strategies

One of the quintessential challenges in cancer treatment is drug resistance.Several mechanisms of drug resistance have been described to date,and new modes of drug resistance continue to be discovered.The phenomenon of cancer drug resistance is now widespread,with approximately 90% of cancer-related deaths associated with drug resistance.Despite significant advances in the drug discovery process,the emergence of innate and acquired mechanisms of drug resistance has impeded the progress in cancer therapy.Therefore,understanding the mechanisms of drug resistance and the various pathways involved is integral to treatment modalities.In the present review,I discuss the different mechanisms of drug resistance in cancer cells,including DNA damage repair,epithelial to mesenchymal transition,inhibition of cell death,alteration of drug targets,inactivation of drugs,deregulation of cellular energetics,immune evasion,tumor-promoting inflammation,genome instability,and other contributing epigenetic factors.Furthermore,I highlight available treatment options and conclude with future directions.

Role of targeting ferroptosis as a component of combination therapy in combating drug resistance in colorectal cancer

Colorectal cancer(CRC)is a form of cancer that is often resistant to chemotherapy,targeted therapy,radiotherapy,and immunotherapy due to its genomic instability and inflammatory tumor microenvironment.Ferroptosis,a type of non-apoptotic cell death,is characterized by the accumulation of iron and the oxidation of lipids.Studies have revealed that the levels of reactive oxygen species and glutathione in CRC cells are significantly lower than those in healthy colon cells.Erastin has emerged as a promising candidate for CRC treatment by diminishing stemness and chemoresistance.Moreover,the gut,responsible for regulating iron absorption and release,could influence CRC susceptibility through iron metabolism modulation.Investigation into ferroptosis offers new insights into CRC pathogenesis and clinical management,potentially revolutionizing treatment approaches for therapy-resistant cancers.

MATHEMATICAL MODELING AND BIFURCATION ANALYSIS FOR A BIOLOGICAL MECHANISM OF CANCER DRUG RESISTANCE

Drug resistance is one of the most intractable issues in targeted therapy for cancer diseases.It has also been demonstrated to be related to cancer heterogeneity,which promotes the emergence of treatment-refractory cancer cell populations.Focusing on how cancer cells develop resistance during the encounter with targeted drugs and the immune system,we propose a mathematical model for studying the dynamics of drug resistance in a conjoint heterogeneous tumor-immune setting.We analyze the local geometric properties of the equilibria of the model.Numerical simulations show that the selectively targeted removal of sensitive cancer cells may cause the initially heterogeneous population to become a more resistant population.Moreover,the decline of immune recruitment is a stronger determinant of cancer escape from immune surveillance or targeted therapy than the decay in immune predation strength.Sensitivity analysis of model parameters provides insight into the roles of the immune system combined with targeted therapy in determining treatment outcomes.

Prox1 Suppresses Proliferation and Drug Resistance of Retinoblastoma Cells via Targeting Notch1

Objective Retinoblastoma(RB)is a prevalent type of eye cancer in youngsters.Prospero homeobox 1(Prox1)is a homeobox transcriptional repressor and downstream target of the proneural gene that is relevant in lymphatic,hepatocyte,pancreatic,heart,lens,retinal,and cancer cells.The goal of this study was to investigate the role of Prox1 in RB cell proliferation and drug resistance,as well as to explore the underlying Notch1 mechanism.Methods Human RB cell lines(SO-RB50 and Y79)and a primary human retinal microvascular endothelial cell line(ACBRI-181)were used in this study.The expression of Prox1 and Notch1 mRNA and protein in RB cells was detected using quantitative real time-polymerase chain reaction(RT-qPCR)and Western blotting.Cell proliferation was assessed after Prox1 overexpression using the Cell Counting Kit-8 and the MTS assay.Drug-resistant cell lines(SO-RB50/vincristine)were generated and treated with Prox1 to investigate the role of Prox1 in drug resistance.We employed pcDNA-Notch1 to overexpress Notch1 to confirm the role of Notch1 in the protective function of Prox1.Finally,a xenograft model was constructed to assess the effect of Prox1 on RB in vivo.Results Prox1 was significantly downregulated in RB cells.Overexpression of Prox1 effectively decreased RB cell growth while increasing the sensitivity of drug-resistant cells to vincristine.Notch1 was involved in Prox1’s regulatory effects.Notch1 was identified as a target gene of Prox1,which was found to be upregulated in RB cells and repressed by increased Prox1 expression.When pcDNA-Notch1 was transfected,the effect of Prox1 overexpression on RB was removed.Furthermore,by downregulating Notch1,Prox1 overexpression slowed tumor development and increased vincristine sensitivity in vivo.Conclusion These data show that Prox1 decreased RB cell proliferation and drug resistance by targeting Notch1,implying that Prox1 could be a potential therapeutic target for RB.

Inferring Mycobacterium Tuberculosis Drug Resistance and Transmission using Whole-genome Sequencing in a High TB-burden Setting in China

Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China.However,molecular epidemiological studies of Kashgar are lacking.Methods A population-based retrospective study was conducted using whole-genome sequencing(WGS)to determine the characteristics of drug resistance and the transmission patterns.Results A total of 1,668 isolates collected in 2020 were classified into lineages 2(46.0%),3(27.5%),and 4(26.5%).The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid(7.4%,124/1,668),streptomycin(6.0%,100/1,668),and rifampicin(3.3%,55/1,668).The rate of rifampicin resistance was 1.8%(23/1,290)in the new cases and 9.4%(32/340)in the previously treated cases.Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains,respectively:18.6%vs.8.7 or 9%,P<0.001.The estimated proportion of recent transmissions was 25.9%(432/1,668).Multivariate logistic analyses indicated that sex,age,occupation,lineage,and drug resistance were the risk factors for recent transmission.Despite the low rate of drug resistance,drug-resistant strains had a higher risk of recent transmission than the susceptible strains(adjusted odds ratio,1.414;95%CI,1.023–1.954;P=0.036).Among all patients with drug-resistant tuberculosis(DR-TB),78.4%(171/218)were attributed to the transmission of DR-TB strains.Conclusion Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.

PHLDA2 reshapes the immune microenvironment and induces drug resistance in hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a malignancy known for its unfavorable prognosis.The dysregulation of the tumor microenvironment(TME)can affect the sensitivity to immunotherapy or chemotherapy,leading to treatment failure.The elucidation of PHLDA2’s involvement in HCC is imperative,and the clinical value of PHLDA2 is also underestimated.Here,bioinformatics analysis was performed in multiple cohorts to explore the phenotype and mechanism through which PHLDA2 may affect the progression of HCC.Then,the expression and function of PHLDA2 were examined via the qRT-PCR,Western Blot,and MTT assays.Our findings indicate a substantial upregulation of PHLDA2 in HCC,correlated with a poorer prognosis.The methylation levels of PHLDA2 were found to be lower in HCC tissues compared to normal liver tissues.Besides,noteworthy associations were observed between PHLDA2 expression and immune infiltration in HCC.In addition,PHLDA2 upregulation is closely associated with stemness features and immunotherapy or chemotherapy resistance in HCC.In vitro experiments showed that sorafenib or cisplatin significantly up-regulated PHLDA2 mRNA levels,and PHLDA2 knockdown markedly decreased the sensitivity of HCC cells to chemotherapy drugs.Meanwhile,we found that TGF-βinduced the expression of PHLDA2 in vitro.The GSEA and in vitro experiment indicated that PHLDA2 may promote the HCC progression via activating the AKT signaling pathway.Our study revealed the novel role of PHLDA2 as an independent prognostic factor,which plays an essential role in TME remodeling and treatment resistance in HCC.

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.

Deciphering resistancemechanisms and novel strategies to overcome drug resistance in ovarian cancer:a comprehensive review

Ovarian cancer is among the most lethal gynecological cancers,primarily due to the lack of specific symptoms leading to an advanced-stage diagnosis and resistance to chemotherapy.Drug resistance(DR)poses the most significant challenge in treating patients with existing drugs.The Food and Drug Administration(FDA)has recently approved three new therapeutic drugs,including two poly(ADP-ribose)polymerase(PARP)inhibitors(olaparib and niraparib)and one vascular endothelial growth factor(VEGF)inhibitor(bevacizumab)for maintenance therapy.However,resistance to these new drugs has emerged.Therefore,understanding the mechanisms of DR and exploring new approaches to overcome them is crucial for effective management.In this review,we summarize the major molecular mechanisms of DR and discuss novel strategies to combat DR.

Comparative Assessment of Genetic Diversity of Peanut (Arachis hypogaea L.)Genotypes with Various Levels of Resistance to Bacterial Wilt Through SSR and AFLP Analyses

Bacterial wilt （BW） caused by Ralstonia solanacearum is an important constraint to peanut （Arachis hypogaea L.） production in several Asian and African countries, and planting BW-resistant cultivars is the most feasible method for controlling the disease. Although several BW-resistant peanut germplasm accessions have been identified, the genetic diversity among these has not been properly investigated, which has impeded efficient utilization. In this study, the genetic relationships of 31 peanut genotypes with various levels of resistance to BW were assessed based on SSR and AFLP analyses. Twenty-nine of 78 SSR primers and 32 of 126 AFLP primer combinations employed in this study were polymorphic amongst the peanut genotypes tested. The SSR primers amplified 91 polymorphic loci in total with an average of 3.14 alleles per primer, and the AFLP primers amplified 72 polymorphic loci in total with an average of 2.25 alleles per primer. Four SSR primers （14H06, 7G02, 3A8, 16C6） and one AFLP primer （P1M62） were found to be most efficient in detecting diversity. The genetic distance between pairs of genotypes ranged from 0.12 to 0.94 with an average of 0.53 in the SSR data and from 0.06 to 0.57 with an average of 0.25 in the AFLP data. The SSR-based estimates of the genetic distance were generally larger than that based on the AFLP data. The genotypes belonging to subsp, fastigiata possessed wider diversity than that of subsp, hypogaea. The clustering of genotypes based on the SSR and AFLP data were similar but the SSR clustering was more consistent with morphological classification ofA. hypogaea. Optimum diverse genotypes of both subsp, hypogaea and subsp.fastigiata can be recommended based on this analysis for developing mapping populations and breeding for high yielding and resistant cultivars.

An Update on the Clinical Pipelines of New Antibacterial Drugs Developed in China

Antibacterial resistance is a global health threat that requires further concrete action on the part of all countries.In this context,one of the biggest concerns is whether enough new antibacterial drugs are being discovered and developed.Although several high-quality reviews on clinical antibacterial drug pipelines from a global perspective were published recently,none provides comprehensive information on original antibacterial drugs at clinical stages in China.In this review,we summarize the latest progress of novel antibacterial drugs approved for marketing and under clinical evaluation in China since 2019.Information was obtained by consulting official websites,searching commercial databases,retrieving literature,asking personnel from institutions or companies,and other means,and a considerable part of the data covered here has not been included in other reviews.As of June 30,2023,a total of 20 antibacterial projects from 17 Chinese pharmaceutical companies or developers were identified and updated.Among them,two new antibacterial drugs that belong to traditional antibiotic classes were approved by the National Medical Products Administration(NMPA)in China in 2019 and 2021,respectively,and 18 antibacterial agents are in clinical development,with one under regulatory evaluation,five in phase-3,six in phase-2,and six in phase-1.Most of the clinical candidates are new analogs or monocomponents of traditional antibacterial pharmacophore types,including two dual-acting hybrid antibiotics and a recombinant antibacterial protein.Overall,despite there being 17 antibacterial clinical candidates,our analysis indicates that there are still relatively few clinically differentiated antibacterial agents in stages of clinical development in China.Hopefully,Chinese pharmaceutical companies and institutions will develop more innovative and clinically differentiated candidates with good market potential in the future research and development(R&D)of original antibacterial drugs.

Multidrug-resistant bacterial infections after liver transplantation: An ever-growing challenge

Bacterial infections are a leading cause of morbidity and mortality among solid organ transplant recipients.Over the last two decades,various multidrug-resistant(MDR)pathogens have emerged as relevant causes of infection in this population.Although this fact reflects the spread of MDR pathogens in health care facilities worldwide,several factors relating to the care of transplant donor candidates and recipients render these patients particularly prone to the acquisition of MDR bacteria and increase the likelihood of MDR infectious outbreaks in transplant units.The awareness of this high vulnerability of transplant recipients to infection leads to the more frequent use of broad-spectrum empiric antibiotic therapy,which further contributes to the selection of drug resistance.This vicious cycle is difficult to avoid and leads to a scenario of increased complexity and narrowed therapeutic options.Infection by MDR pathogens is more frequently associated with a failure to start appropriate empiric antimicrobial ther-apy.The lack of appropriate treatment may contribute to the high mortality occurring in transplant recipients with MDR infections.Furthermore,high therapeutic failure rates have been observed in patients infected with extensively-resistant pathogens,such as carbapenemresistant Enterobacteriaceae,for which optimal treatment remains undefined.In such a context,the careful implementation of preventive strategies is of utmost importance to minimize the negative impact that MDR infections may have on the outcome of liver transplant recipients.This article reviews the current literature regarding the incidence and outcome of MDR infections in liver transplant recipients,and summarizes current preventive and therapeutic recommendations.

Effects of Taxotere on invasive potential and multidrug resistance phenotype in pancreatic carcinoma cell line SUIT-2

INTRODUCTIONDevelopment of drug-resistance to chemotherapyand subsequent metastasis of tumor are primarilyresponsible for treatment failure and the death fromcancer. There have been many previous studies onthe relationship between expression of multidrugresistance (MDR) phenotype P-glycoprotein (P-gp)and the malignant properties of tumors, but theresults are often conflicting[1-8]. The difference intumor types or MDR phenotype induced by specificagents might account for this discrepancy. Taxotere(TXT), a member of the family of taxanes, hasantitumor activity through its effect of promotingthe polymerization of tubulin[9,10].

Drug sensitivity and drug resistance profiles of human intrahepatic cholangiocarcinoma cell lines

AIM: To study the effect of a number of chemotherapeutic drugs on five human intrahepatic cholangiocarcinoma (CCA) cell lines. The expressions of genes that have been proposed to influence the resistance of chemotherapeutic drugs including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), glutathione-S-transferase PI (GSTP1), multidrug resistance protein (MDR1) and multidrug resistance-associated proteins (MRPs) were also determined. METHODS: Five human CCA cell lines (KKU-100, KKU-M055, KKU-M156, KKU-M214 and KKU-OCA17) were treated with various chemotherapeutic drugs and growth inhibition was determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Semi-quantitative levels of gene expression were determined by a reverse transcriptase polymerase chain reaction (RT-PCR). Results of IC_(50) values and the ratios of gene expression were analyzed by linear regression to predict their relationship. RESULTS: Among five CCA cell lines, KKU-M055 was the most sensitive cell line towards all chemotherapeutic drugs investigated, particularly taxane derivatives with IC_(50) values of 0.02-3 nmol/L, whereas KKU-100 was apparently the least sensitive cell line. When compared to other chemotherapeutic agents, doxorubicin and pirarubicin showed the lowest IC_(50) values (＜5 μmol/L) in all five CCA cell lines. Results from RT-PCR showed that TS, MRP1, MRP3 and GSTP1 were highly expressed in these five CCA cell lines while DPD and MRP2 were only moderately expressed. It should be noted that MDR1 expression was detected only in KKU-OCA17 cell lines. A strong correlation was only found between the level of MRP3 expression and the IC_(50) values of etoposide, doxorubicin and pirarubicin (r=0.86-0.98, P＜0.05). CONCLUSION: Sensitivity to chemotherapeutic agents is not associated with the histological type of CCA. Choosing of the appropriate chemotherapeutic regimen for the treatment of CCA requires knowledge of drug sensitivity. MRP3 was correlated with resistance of CCA cell lines to etoposide, doxorubicin and pirarubicin, whereas other chemotherapeutic drugs showed no association. The role of this multidrug resistance-associated protein, MRP3, in chemotherapeutic resistance in CCA patients needs to be further investigated.

Distribution and drug resistance of pathogens in burn patients in China from 2006 to 2019

BACKGROUND In this study,recent trends in the distribution and drug resistance of pathogenic bacteria isolated from patients treated at a burn ward between 2006 and 2019 were investigated.AIM To develop more effective clinical strategies and techniques for the prevention and treatment of bacterial infections in burn patients.METHODS Clinical samples with positive bacteria were collected from patients at the burn ward in Beijing Jishuitan Hospital in China between January 2006 and December 2019.The samples were retrospectively analyzed,the distribution of pathogenic bacteria was determined,and the trends and changes in bacterial drug resistance during different period were assessed.Drug resistance in several main pathogenic bacteria from 2006 to 2011 and from 2012 to 2019 was comparatively summarized and analyzed.RESULTS Samples from 17119 patients were collected and analyzed from 2006 to 2019.Surprisingly,a total of 7960 strains of different pathogenic bacteria were isolated at this hospital.Among these bacteria,87.98%(7003/7960)of the strains were isolated from burn wounds,and only 1.34%(107/7960)were isolated from the blood of patients.In addition,49.70%(3956/7960)were identified as Grampositive bacteria,48.13%(3831/7960)were Gram-negative bacteria,and the remaining 2.17%(173/7960)were classified as fungi or other pathogens.Importantly,Staphylococcus aureus(21.68%),Pseudomonas aeruginosa(14.23%),and Staphylococcus epidermidis (9.61%) were the top three pathogens most frequentlyisolated from patients.CONCLUSION In patients treated at the burn ward in this hospital from 2006 to 2019,Staphylococcus aureus and Pseudomonas aeruginosa were the predominant clinicalpathogens responsible for bacterial infections. The circumstantial detection anddetailed monitoring of the intensity and growth of different pathogenic bacteria inclinical patients as well as tests of drug sensitivity during burn recovery areparticularly important to provide guidelines for the application of antibiotics andother related drugs. Careful collection and correct, standard culture of bacterialspecimens are also crucial to improve the efficiency of bacterial infectiondetection. Effective monitoring and timely clinical treatment in patients may helpreduce the possibility and rate of infection as well as alleviate the effects of drugresistance among patients in burn centers.

Antibacterial resistance patterns of Acinetobacter baumannii complex:The results of Isfahan Antimicrobial Resistance Surveillance-1 Program

Objective: To determine the antibiotic resistance patterns of the Acinetobacter(A.) baumannii complex isolates that cause the confirmed infection. Methods: The present descriptive study was performed from March 2016 to March 2018 in three referral hospitals in Isfahan, Iran. All A. baumannii complex strains isolated from different clinical samples were identified by conventional phenotypic methods and antibiotic susceptibility pattern was detected. After the clinical investigation, contaminated samples were excluded and the source(hospital/community) and site of the infection were determined. Data on antibiotic susceptibility testing were extracted from WHONET software and analysis was done with SPSS.Results: From 254 patients who had confirmed A. baumannii complex infection, 158(62.20%) cases were male, 27(10.63%) were less than 20 years old, 172(67.72%) had healthcare-associated infections and 96(37.79%) were admitted in intensive care units. The most frequent infection was bloodstream infections(111, 43.70%). Our results showed that most of the isolates were resistant to most of the antibiotics(more than 75.00%) and a lower rate of non-susceptibility was observed against minocycline(20, 44.44%) and colistin(0%). The rate of multidrug-resistant isolates was 88.97%. There was no significant difference between resistance of A. baumannii complex isolates according to age. However, the resistance to amikacin and minocycline and the rate of multidrug resistance(MDR) were significantly different between males and females. In patients with healthcare associated infection(HAI), MDR isolates were significantly different regarding admission in ICU ward. Resistance to levofloxacin and ciprofloxacin were lower in isolates from patients with bloodstream infections in comparison to other diagnoses.Conclusions: In our study, a high level of antibiotic resistance was detected in both community-acquired and healthcare-associated A. baumannii complex infections. Appropriate antibiotic prescription in a clinical setting is an essential need for the control and prevention of A. baumannii resistant infections.

Isolation and Drug Resistance Analysis of Swine Salmonella

In this study, 68 fresh pork samples were collected from several major wholesale markets in Dalian City of Liaoning Province to isolate Salmonella using SS agar medium as selective medium. Salmonella isolates were identified with colony morphology observation and PCR method. The resistance of Salmonella iso- lates to 15 antibiotics was analyzed by broth microdilution susceptibility test. Accord- ing to the result, 12 Salmonella strains were isolated from 68 fresh pork samples, indicating a detection rate of 17.64%; 83.33% of Salmonella strains isolated from fresh pork samples could at least resist one antibiotic; Salmonella strains exhibited the strongest resistance to florfenicol （75.0%）, sarafloxacin hydrochloride （66.7%）, neomycin sulfate （66.7%） and doxycycline hydrochloride （66.7%）, followed by oxyte- tracycline （58.3%）, gentamicin sulphate （58.3%） and mequindox （58.3%）; Salmonella strains exhibited relatively low resistance to ciprofloxacin lactate （50.0%）, en- rofloxacin （50.0%）, ciprofloxacin hydrochloride （50.0%）, amoxicillin （16.7%） and col- istin sulphate （16.7%）. Salmonella in fresh pork samples from wholesale markets in Dalian Economic ＆ Technological Development Zone exhibited a high detection rate, and the isolated Salmonella strains showed extremely high resistance to various an- tibiotics. The strong drug-resistance of Salmonella can also be transmitted through the food chain from the food to the people, which should attract sufficient attention.

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.