Distribution and drug resistance of pathogenic bacteria isolated from cancer hospital in 2013

Objective： To understand distribution and drug resistance of pathogenic bacteria from a specialized cancer hospital in 2013 in order to provide a basis for rational clinical antimicrobial agents. Methods： Pathogenic bacteria identification and drug sensitivity tests were performed with a VITEK 2 compact automatic identification system and data were analyzed using WHONET5.6 software.Results： Of the 1,378 strains tested, 980 were Gram-negative bacilli, accounting for 71.1%, in which Klebsiella pneumonia, Escherichia coli and Pseudomonas aeruginosa were the dominant strains. We found 328 Gram-positive coccus, accounting for 23.8%, in which the amount of Staphylococcus aureus was the highest. We identified 46 fungi, accounting for 4.1%. According to the departmental distribution within the hospital, the surgical departments isolated the major strains, accounting for 49.7%. According to disease types, lung cancer, intestinal cancer and esophagus cancer were the top three, accounting for 20.9%, 17.3% and 14.2%, respectively. No strains were resistant to imipenem, ertapenem or vancomycin.Conclusions： Pathogenic bacteria isolated from the specialized cancer hospital have different resistance rates compared to commonly used antimicrobial agents; therefore antimicrobial agents to reduce the morbidity and mortality of infections should be used.

A tumor-penetrable drug nanococktail made from human histones for interventional nucleus-targeted chemophotothermal therapy of drug-resistant tumors

Nanoparticle-based chemophotothermal therapy(CPT)is a promising treatment for multidrug resistant tumors.In this study,a drug nanococktail of DIR825@histone was developed by employing doxorubicin(DOX),NIR dye IR825 and human histones for interventional nucleus-targeted CPT of multidrug resistant tumors with an interventional laser.After localized intervention,DIR825@histone penetrated tumor tissues by transcytosis,efficiently entered tumor cells and targeted the cell nuclei.DIR825@histone also exhibited good photothermal performance and thermal-triggered drug release.Efficient multidrug resistant tumor inhibition was achieved by enhanced CPT sensitization and MDR reversion via nuclear targeting.Moreover,an interventional laser assisted DIR825@histone in inhibiting multidrug resistant tumors by promoting the sufficient delivery of laser energy inside the tumor while reducing skin injury.Therefore,DIR825@histone together with this interventional nucleus-targeted CPT strategy holds great promise for treating multidrug resistant tumors.

Phytic acid-modified CeO_(2) as Ca^(2+) inhibitor for a security reversal of tumor drug resistance

Ca^(2+)plays critical roles in the development of diseases,whereas existing various Ca regulation methods have been greatly restricted in their clinical applications due to their high toxicity and inefficiency.To solve this issue,with the help of Ca overexpressed tumor drug resistance model,the phytic acid(PA)-modified CeO_(2) nano-inhibitors have been rationally designed as an unprecedentedly safe and efficient Ca2+inhibitor to successfully reverse tumor drug resistance through Ca^(2+)negative regulation strategy.Using doxorubicin(Dox)as a model chemotherapeutic drug,the Ca^(2+)nano-inhibitors efficiently deprived intracellular excessive free Ca2+,suppressed P-glycoprotein(P-gp)expression and significantly enhanced intracellular drug accumulation in Dox-resistant tumor cells.This Ca^(2+)negative regulation strategy improved the intratumoral Dox concentration by a factor of 12.4 and nearly eradicated tumors without obvious adverse effects.Besides,nanocerias as pH-regulated nanozyme greatly alleviated the adverse effects of chemotherapeutic drug on normal cells/organs and substantially improved survivals of mice.We anticipate that this safe and effective Ca^(2+)negative regulation strategy has potentials to conquer the pitfalls of traditional Ca inhibitors,improve therapeutic efficacy of common chemotherapeutic drugs and serves as a facile and effective treatment platform of other Ca^(2+) associated diseases.

Validation of single nucleotide polymorphisms potentially related to R-CHOP resistance in diffuse large B-cell lymphoma patients

Aim:Diffuse large B-cell lymphoma(DLBCL)is the most common B-cell non-Hodgkin lymphoma(NHL).Despite the availability of clinical and molecular algorithms applied for the prediction of prognosis,in up to 30%-40%of patients,intrinsic or acquired drug resistance occurs.Constitutional genetics may help to predict R-CHOP resistance.This study aimed to validate previously identified single nucleotide polymorphisms(SNPs)in the literature as potential predictors of R-CHOP resistance in DLBCL patients,SNPs.Methods:Twenty SNPs,involved in R-CHOP pharmacokinetics/pharmacodynamics or other pathobiological processes,were investigated in 185 stage Ⅰ-Ⅳ DLBCL patients included in a multi-institution pharmacogenetic study to validate their previously identified correlations with resistance to R-CHOP.Results:Correlations between rs2010963(VEGFA gene)and sex(P=0.046),and rs1625895(TP53 gene)and stage(P=0.003)were shown.After multivariate analyses,a concordant effect(i.e.,increased risk of disease progression and death)was observed for rs1883112(NCF4 gene)and rs1800871(IL10 gene).When patients were grouped according to the revised International Prognostic Index(R-IPI),both these SNPs further discriminated progression-free survival(PFS)and overall survival(OS)of the R-IPI-1-2 subgroup.Overall,patients harboring the rare allele showed shorter PFS and OS compared with wild-type patients.Conclusions:Two out of the 20 study SNPs were validated.Thus,these results support the role of previously identified rs1883112 and rs1800871 in predicting DLBCL resistance to R-CHOP and highlight their ability to further discriminate the prognosis of R-IPI-1-2 patients.These data point to the need to also focus on host genetics for a more comprehensive assessment of DLBCL patient outcomes in future prospective trials.