ObjectiveTo explore the relationship between imipenem-resistant Pseudomonas aeruginosa (IRPA) and outer membrane porin protein OprD2 gene mutation.MethodsIRPA strains (n=30) and imipenem-sensitive Pseudomonas aeruginosa strains (n=30) isolated from the clinical specimens in the First Affiliated Hospital of Chengdu Medical College from December 2018 to December 2019 were collected. Bacteria identification and drug sensitivity experiments were performed by VITEK-2 Compact combined with Kirby-Bauer method. Quantitative real-time polymerase chain reaction was used to detect the expression levels of OprD2 gene in the imipenem-resistant group and the imipenem-sensitive group, and then the strains with decreased expression were sequenced.ResultsThe expression level of OprD2 gene in the imipenem-resistant group was significantly lower than that in the imipenem-sensitive group (P=0.048). Compared with the X63152 sequence, all the 11 Pseudomonas aeruginosa strains with significantly decreased OprD2 expression carried genetic variation, which occurred in coding regions. The variation sites presented diversity. The missense mutation of c.308C→G, c.344A→C, c.379G→C, c.471G→C, c.508T→C, c.553G→C, c.556-558CCG→GGC and c.565-566TG→AC caused amino acid change in the loop L2 and L3 of OprD2 porin, which affected the binding to imipenem. In addition, the mutations at 127, 169-171, 175, 177, 604, 628-630, 688, 719, 785, 826, 828, 842-843, 886, 901, 928-930, 934, 936, 944-945, 1039, 1041 and 1274 all resulted in the changes of amino acid. We also detected a deletion (c.1114-1115delAT) and other nonsense mutations. Large fragment deletion of OprD2 gene occurred in Strain 12. ConclusionsThe mutation and deletion of OprD2 gene can reduce the expression lever of OprD2 gene, leading to the resistance to imipenem of Pseudomonas aeruginosa. The variation of OprD2 gene of IRPA from clinical strains is diverse.
Objective To summarize the papers about the research status and prospects of ferroptosis in hepatocellular carcinoma (HCC) and its drug resistance in recent years in order to provide directions and ideas for the treatment of HCC. Method The relevant literatures at home and abroad in recent years about ferroptosis in HCC and its drug resistance were reviewed. Results The mechanism of ferroptosis in the development and drug resistance of HCC was complicated, involving multiple protein and molecular pathways. Ferroptosis played an important role in improving chemotherapy and sorafenib resistance, and it had a broad application prospect in HCC. Conclusions The molecular mechanism of ferroptosis in HCC and its drug resistance has not been fully elucidated. Further research on the mechanism of ferroptosis in HCC may provide new molecular therapeutic targets for HCC. Ferroptosis has a broad application prospect in the treatment of HCC.
In recent years, with the wide application of carbapenems, the resistance of Enterobacterium to carbapenems has become increasingly high, leading to a large number of carbapenem-resistant Klebsiella pneumoniae (CRKP). These bacteria are often resistant to many different types of antibacterial drugs, including carbapenems, which leads to clinical treatment failure and seriously threatens the life safety of patients. Currently, these bacteria have become an independent risk factor for patients’ death. This article reviews the drug resistance, infection status and influencing factors, and medication therapy of CRKP, in order to facilitate the clinical diagnosis, treatment, and disease process control of CRKP infection, and provide reference for curbing bacterial drug resistance.
ObjectiveTo systematically elucidate the resistance mechanism of targeted drug therapy for breast cancer and to discuss the future direction of optimized treatment strategies. MethodA literature review on targeted therapy for breast cancer had been conducted based on recent domestic and international researches. ResultsContemporary breast cancer targeted therapies maincomprised human epidermal growth factor receptor 2 (HER2)-directed agents, CDK4/6 inhibitors, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT) / mechanistic target of rapamycin (mTOR) pathway blockers, poly (ADP-ribose) polymerase inhibitors, and immune checkpoint modulators, etc. While these agents conferred subtype-specific survival benefits, resistance developed through target mutations, compensatory signaling, epigenetic alterations, drug efflux pumps, etc. Emerging reversal drug resistance strategies involved dual-targeted approaches (such as trastuzumab in combination with pertuzumab), dynamic monitoring of drug-resistant gene mutations by liquid biopsy, epigenetic modulators, etc. ConclusionsDrug resistance remains a key bottleneck limiting long-term efficacy of breast cancer targeted therapy. Future research should integrate multi-omics approaches to decipher tumor heterogeneity, implement combinatorial multi-target inhibition with real-time monitoring of multidimensional interventions, and leverage artificial intelligence to predict resistance evolution. This integrated strategy will enable personalized combination therapies, ultimately overcoming drug resistance and improving patient survival outcomes.