Objective To review the application advancements of ATP-binding cassette (ABC) transporter in medical research.Methods Relevant literatures about the applications of ABC families in medical research were reviewed. Results ABC families mainly took roles in transporting substances across cell membrane. Some of them were useful for the prediction of drug resistance and the prognosis of malignant tumors. Others were target s for molecular researches. Their expressions or mutations might be related with the occurrence of diseases. Conclusion ABC families are very important in the diagnosis and therapy for diseases. Thus they are very promising tools for future medical research.
Objective To compare the infection characteristics and pathogen resistance between dialysis and non-dialysis patients with chronic kidney disease (CKD) in West China Hospital of Sichuan University, and provide a reference for clinical diagnosis and treatment. Methods The clinical data of CKD patients with non-repeated etiological evidence admitted to West China Hospital of Sichuan University between January 2010 and December 2021 were retrospectively analyzed. The patients were divided into dialysis group and non-dialysis group according to treatment methods. The infection characteristics and pathogen resistance of the two groups were analyzed by WHONET 5.6 and SPSS 23 softwares. Results A total of 1387 patients with CKD with positive etiology were included, excluding coagulase-negative Staphylococcus, which was common contamination pathogens of bloodstream infections. There were 527 patients in the dialysis group and 860 patients in the non-dialysis group in this study. There was no significant difference in gender between the two groups (P>0.05). There were significant differences in age, disease stage and specimen type between the two groups (P<0.01). The pathogenic bacteria samples of dialysis patients were mainly blood (25.81%) and dialysate (44.02%), and Staphylococcus aureus was the main pathogenic bacteria. In the non-dialysis group, sputum (49.88%) and urine (35.47%) were the main contents. In main Gram-positive pathogens, there were high resistance rates to penicillin and cephalosporin, and high sensitive rates to vancomycin and linezolid. In Gram-negative pathogenic bacteria, there were high resistance rates to penicillins, the first generation cephalosporins and the third generation cephalosporins, and high sensitive rates to β-lactamase inhibitor compound preparation, the fourth generation cephalosporins and other antibiotics. Conclusions CKD patients are easy to be complicated with infections. In clinical practice, it is necessary to pay attention to pathogen culture results, and selectively use antibiotics based on drug sensitivity results. At the same time, medical staff in hemodialysis centers should pay attention to aseptic operation and hand hygiene to reduce the risk of concurrent infection in dialysis patients.
ObjectiveTo investigate the value of serum soluble CD146 (sCD146) in determining acquired epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance in lung adenocarcinoma.MethodsA total of 144 lung adenocarcinoma EGFR sensitive patients in People’s Hospital of Zhengzhou University diagnosed from January 2016 to December 2016 were recruited in the study. According to the different time of taking drugs, the patients were divided into a non-medication group (31 cases), a 1 to 3 month treatment group (25 cases), a 4 to 6 month treatment group (19 cases), a 7 to 12 month treatment group (25 cases), a drug-resistant group (24 cases), and a nonresistant group up to 1 year of treatment (20 cases). The serum levels of sCD146, carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) were measured by ELISA and chemiluminescence and compared between different period of medication. The relationship of serum sCD146 with tumor markers (CEA, NSE) and tumor related clinical parameters (age, gender, tumor stage, metastasis, tumor diameter, number of the lesions) were analyzed.ResultsThe serum sCD146 level was minimum in the non-medication group that did not receive pioglitazone treatment, highest in the 1 to 3 month treatment group (early treatment period), and declined with duration of medication until resistance occurred without significant difference (P>0.05). The level of sCD146 of the drug-resistant group was significantly lower than that of all nonresistant groups, with significant difference (allP<0.05), but still higher than that of the non-medication group (P<0.05). The serum sCD146 levels in the nonresistant patients with medication over 1 year and within 1 year were similar (P>0.05), and significantly higher than the non-medication group and drug-resistance group (allP<0.05). The serum CEA levels did not differ significantly between 6 groups (P>0.05). The serum NSE level of the 4 to 6 month treatment group was lower than that of the 7 to 12 month treatment group (P<0.05), but both in the normal reference range. The NSE levels did not differ in any other groups (P>0.05). Serum sCD146 was associated with metastasis (P<0.05), but not associated with serum CEA or NSE, nor with sex, age, tumor staging, tumor diameter or lesion number (allP>0.05).ConclusionsCD146 may be involved in the mechanism of TKI killing tumor cells and the mechanism of TKI resistance, and may be a serological marker for monitoring the efficacy of TKI and judging the resistance of TKI.
ObjectiveTo systematically elucidate the resistance mechanism of targeted drug therapy for breast cancer and to discuss future direction of optimized treatment strategies. MethodA literature review on targeted therapy for breast cancer had been conducted based on recent domestic and international research. ResultsContemporary breast cancer targeted therapies mainly comprised human epidermal growth factor receptor 2 (HER2)-directed agents, CDK4/6 inhibitors, phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin pathway blockers, poly (ADP-ribose) polymerase inhibitors, and immune checkpoint modulators, etc. While these agents had conferred subtype-specific survival benefits, resistance developed through target mutations, compensatory signaling, epigenetic alterations, drug efflux pumps, among other mechanisms. Emerging strategies for reversing drug resistance included 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 is expected to enable personalized combination therapies, ultimately overcoming drug resistance and improving patient survival outcomes.
ObjectiveTo summarize the biological function and molecular regulation mechanism of serine threonine tyrosine kinase 1 (STYK1) in tumor occurrence and development. MethodThe relevant literature about STYK1 and tumor progression in recent years was searched and reviewed. ResultsThe expression of STYK1 was up-regulated in a variety of tumors and was related to the prognosis. STYK1 might regulate the proliferation, apoptosis, migration, metastasis, aerobic glycolysis, drug resistance and other biological functions of tumor cells through MEK/ ERK, PI3K/AKT, JAK/STAT and their targeting proteins, and promote the malignant progress of tumors. Conclusion STYK1is expected to become a new target for the treatment of malignant tumors, but the molecular mechanism of its regulation of tumor progression and its upstream regulators need to be further explored.
Objective To study the expression and significance of multidrug resistance-associated protein (MRP) gene in hepatocellular carcinoma (HCC). Methods Reverse transcription polymerase chain reaction (RT-PCR) assay was used to detect the expression of MRP mRNA in 25 fresh specimens of the primary HCC and its surrounding liver tissues. Immunohistochemistry LSAB technique was adopted to test MRP in 60 HCC specimens. The drug sensitivity was also tested by flow cytometry.Results The positive expression rates of MRP mRNA and MRP protein in primary HCC were 44.00%(11/25) and 45.00%(27/60) respectively. All the intensity of expression was low, but significant higer than its surrouding liver tissues (P＜0.05). The intensity and expression rate of MRP protein in 5 recurrent HCC had a tendency to increase. There was a correlation between the expression of MRP mRNA and MRP protein in 25 patients using RT-PCR and immunohistochemistry assay (Plt;0.05). Detected by flow cytometry, the average sensitivity of drugs in vitro of 60 HCC sp-cimens were 5-FU （15.80±7.63）%，DDP（18.45±9.59）%，ADM（17.95±7.99）%，MMC（16.60±8.69）% and CTX（17.40±10.14）%. Only 5FU and ADM were significantly affected by the expression of MRP protein (Plt;0.05).Conclusion The expression of MRP in primary HCC may be one of the important mechanisms of the intrinsic and acquired drug resistance in HCC. To study the expression of MRP could give a predictive value in HCC chemotherapy.
ObjectiveTo construct the recombinant adenovirus vector carrying antisense multidrug resistanceassociated protein (MRP) and transfect the human drugresistant hepatocellular carcinoma cell line(SMMC7721/ADM). MethodsThe fragment of MRP gene encoding 5′region was cloned reversely into the shuttle plasmid pAdTrackCMV, with the resultant plasmid and the backbone plasmid pAdEasy1,the homologous recombination took place in the bacteria and the recombinant adenoviral plasmid was generated. The adenoviruses were packaged and amplified in 293 cells. Then the cell line of SMMC7721/ADM was transfected with the resultant adenoviruses.ResultsThe recombinant adenovirus vector carrying antisense MRP was constructed successfully. The viral titer was 2.5×109 efu/ml, and more than 90% SMMC7721/ADM cells could be transfected when the multiplicity of infection（MOI） was 100. ConclusionThe recombinant adenovirus vector constructed by us could introduce the antisense MRP into the human drugresistant hepatocellular cell line effectively, which would provide experimental basis for the mechanisms and reversal methods of the multidrug resistance in human hepatocellular carcinoma.
ObjectiveTo systematically review the therapeutic effects and safety of teicoplanin versus vancomycin for severe gram-positive bacterial infection.
MethodsWe electronically searched CBM, CNKI, VIP, WanFang Data, PubMed, EMbase, The Cochrane Library (Issue 3, 2013) and Springer for the internationally-nationally published randomized controlled trials (RCTs) on teicoplanin versus vancomycin for severe gram-positive bacterial infections from inception to October 2013. Two reviewers screened literature according to the inclusion and exclusion criteria, extracted data, and assessed the methodological quality of the included studies. Then meta-analysis was performed using RevMan 5.2 software.
ResultsTwenty RCTs were finally included, involving 1 555 patients with severe gram-positive bacterial infection. The results of meta-analysis showed that there was no significant difference between teicoplanin and vancomycin with regard to all-cause mortality (OR=1.67, 95%CI 0.86 to 3.23, P=0.13), clinical cure rates (OR=1.24, 95%CI 0.95 to 1.60, P=0.11), effective rates (OR=1.03, 95%CI 0.75 to 1.41, P=0.87), and bacterial clearance rates (OR=0.96, 95%CI 0.66 to 1.39, P=0.83). However, the incidence of adverse reaction was lower in the teicoplanin group than in the vancomycin with a significant difference (OR=0.50, 95%CI 0.34 to 0.72, P=0.000 2).
ConclusionThe results of meta-analysis shows that, teicoplanin is similar to vancomycin in therapeutic effects on treating severe gram-positive bacterial infection but it is better in safety. However, because of limited quantity and quality of the included studies, the above conclusion needs to be further verified by conducting more high-quality studies.
ObjectiveTo establish multidrugresistance cell substrain of human hepatocellular carcinoma and to investigate its characteristics.MethodsSMMC7721 cell strain was cultured in Adriamycin(ADM). The multidrugresistance cell substrain SMMC7721/ADM was harvested after a long period of culture by gradually increasing the concentration of ADM and its characteristics were investigated. Results①The drug resistance of SMMC7721/ADM to ADM increased by 33.3 times, to Vincristine 16.8 times, to Diamminedichloroplatinum 2.8 times. ②The drug resistance cell substrain had almost the same growth velocity as its parental generation. The doubling time was 32.0 hours and 30.5 hours respectively. They had the analogous growth curves. ③The obvious difference between the drug resistance cell substrain and its parental generation was that the former’s microvilli became thick, short and scattered by scanning and transmitting electron microscopy. ④The multidrug resistance cell substrain kept the characteristics of hepatocellular carcinoma, it could be transplanted into the subcutaneous tissue of nude mice. ⑤The drug resistance of the cell substrain reduced to 28.0% and 9.2%after removal of the drug for 1 month and 2 months respectively, its drug resistance could remain stable (35.4 times) after 2 months of culture in ADM (0.04 μg/ml).ConclusionThe SMMC7721/ADM cell substrain has the stable fundamental characteristics of a drug resistance cell strain.
Objective To investigate the clinical characteristics and drug sensitivity of patients with Gram-negative bacilli infection, and evaluate the risk factors related to infection, so as to provide a theoretical basis for clinical prevention and treatment of hospital-acquired infection. Methods The complete medical records of 181 patients with Gram-negative bacilli infection in the Department of Respiratory and Critical Care Medicine of Beijing Anzhen Hospital from January 2018 to September 2021 were retrospectively collected. They were divided into a Carbapenem-resistant Gram-negative bacillus (CR-GNB) group and a Carbapenem-sensitive Gram-negative bacillus (CS-GNB) group according to their different sensitivities to carbapenems. Results A total of 238 strains of Gram-negative bacilli were detected, including 108 strains of CR-GNB and 130 strains of CS-GNB. Acinetobacter baumannii was the most common, followed by Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli and Serratia marcescens. Univariate analysis showed that the risk factors of CR-GNB infection were heart disease and cerebrovascular disease, receiving invasive mechanical ventilation, deep venous catheterization and indwelling catheter, hypoproteinemia, renal insufficiency, pre-infection exposure to tigecycline, carbapenems, vancomycin, polymyxin, and combined use of antibiotics. Hypoproteinemia and deep venous catheterization were independent risk factors for CR-GNB infection. The resistance rates of CR-GNB to cefepime, ceftazidime, levofloxacin and ciprofloxacin were 88.0%, 88.0%, 86.1% and 75.0%, respectively. The resistance rate to cefuroxime, amika, ceftriaxone, gentamicin and cotrimoxazole was low, and the resistance rate to ceftazidime avibactam was the lowest (3.7%). Except tetracycline, tigecycline, cefuroxime, polymyxin, cefazolin and ampicillin, the drug resistance rates of CR-GNB group to other antibacterial drugs were higher than those of CS-GNB group, and the differences were statistically significant (P<0.05). The all-cause mortality in CR-GNB group (42.4%) was significantly higher than that in CS-GNB group (6.3%), and the difference was statistically significant (P<0.05). Conclusions The disease burden caused by CR-GNB infection is becoming heavier and heavier, which has a serious impact on the prognosis of hospitalized patients. The increase of antibiotic resistance leads to poor efficacy of antimicrobial therapy. Therefore, early identification of high-risk groups of infection and reasonable and prudent application of antimicrobial therapy can achieve the purpose of reducing the mortality of infection and improving the prognosis of hospitalized patients.
