ObjectiveTo investigate the molecular mechanism by which metastasis-associated protein 3 (MTA3) participates in glioma resistance through reactive oxygen species. Methods Protein expression in glioma stem cells (GSCs) and non-GSCs was detected using Western blotting. GSCs included U87 and SHG44 cells, while non-GSCs included U87s and SU-2 cells. After overexpressing MTA3, U87 and SHG44 cells were divided into Lv-scr and Lv-MTA3 groups. The self-renewal capacity of glioma cells was assessed through a neurosphere formation assay. Cell survival fractions were examined following exposure to 0, 2, 4, 6, 8, and 10 Gy X-ray irradiation under normoxic or hypoxic conditions. Apoptosis and reactive oxygen species expression were analyzed using flow cytometry. Immunofluorescence staining was performed to detect the stem cell markers CD133 and nestin, as well as the differentiation markers glial fibrillary acidic protein (GFAP, for astrocytes) and neuronal class Ⅲ β-tubulin. Results In GSCs, MTA3 expression was lower in the U87s and SU-2 groups. After MTA3 overexpression, Lv-MTA3 expression was higher in U87s and SU-2 compared to the Lv-scr group. Under normoxic or hypoxic conditions, U87 and SU-2 showed greater radioresistance compared to glioma cell lines U87 and SHG44. Compared to non-GSCs, basal reactive oxygen species formation was reduced in GSCs, while reactive oxygen species generation was increased in non-GSCs. Following exposure to different doses of X-rays under normoxic or hypoxic conditions, GSCs with MTA3 overexpression exhibited greater radiosensitivity than those with stable integration. Additionally, MTA3 overexpression slightly increased the oxygen enhancement ratio (OER) in GSCs. MTA3 overexpression reduced the immunoreactivity of CD133 and nestin in both stem cell lines, and increased immunofluorescence staining of GFAP and neuronal class Ⅲ β-tubulin, with statistically significant differences (P<0.05). Conclusions MTA3 is downregulated in GSCs. Overexpression of MTA3 reduces the radioresistance and stemness of GSCs both in vitro and in vivo. MTA3 plays a crucial role in regulating the radiosensitivity and stemness of GSCs through reactive oxygen species.
Objective To investigate the reversal of the multidrug resistant gene mdr1 in vivo by antisense oligodeoxynucleotide （ASODN） on the basis of study in vitro. Methods The cultured drug-resistant human hepatocellular carcinoma cells were injected under the skin of axilla to establish the tumor model of nude mice. mdr1 ASODN accompanied by Lipofectamine were injected locally and ADM was injected intraperitoneally. Control 1 and control 2 were locally injected by Lipofectamine and normal saline separately, and ADM was also injected intraperitoneally. Results As time went on the tumor size increased and from the 5th day on alterations were marked, tumor size in different time phase showed marked difference to the prior time phase with significant difference (P＜0.05）. Tumor size in group ASODN was marked smaller than that of other 3 groups after the 5th day (P＜0.05)，while tumor size of group control 1,2 and group SODN in different phase showed no significant difference (Pgt;0.05). The results suggested that SODN and Lipofectamine showed no marked effect on tumor growth of nude mice and ASODN had marked inhibition effect on tumor growth. Conclusion mdr1 ASODN can also reverse multidrug resistance of drug-resistant human hepatocellular carcinoma cells in vivo. After the treatment the tumor’s growth in nude mice will slow down in a range of time.
Objective To investigate the reversal effect of antisense phosphorothioate oligonucleotide （ASOND) on human hepatoma resistant cells. Methods Human hepatoma resistant cells SMMC-7721 was transfected with synthetic antisense phosphorothioate oligonucleotide complementary to the 5′ region flanking the AUG initiation codon mediated by lipofectamine. In vitro drug sensitivity was measured by MTT assay. The expression of P-170 was determined by flow cytometry and mRNA was assessed by RT-PCR. Results ASOND inhibited the expression of mRNA and p-170 in SMMC-7721, enhanced the sensitivity of SMMC-7721 to chemotherapeutic drug. The best inhibitory effect was achived by the dose of 0.5μmol/L. Conclusion ASOND enhanced the sensitivity of SMMC-7721 to chemotherapeutic drug and reversed the multidrug resistance of SMMC-7721 partially.
Objective To investigate the effect of phosphorothioate antisense oligonucleotides(AS-ODN) on suppressing multidrug resistance-associated protein gene(MRP) in human drug-resistant hepatocellular carcinoma cell line (SMMC-7721/ADM). Methods Cell line was transfected with a synthetic S-ODN complementary to the coding region of MRP mRNA, Lipofectamine acting as carrier. The drug sensitivity was measured by MTT assay. The expression of MRP mRNA was detected by RT-PCR and the expression of P190 was detected by flow cytometry. Results AS-ODN inhibited expression of MRP mRNA and P190 and promoted sensitivity to daunorubicinum and adriamycinum. Conclusion AS-ODN can reduce the expression of MRP gene. MDR caused by MRP is an important cause of multidrug resistance of SMMC-7721/ADM.
Objective To investigate nosocomial non-fermented bacterial infection in lower respiratory tract and the risk factors for multi-drug resistant bacterial infection. Methods 229 patients with nosocomial nonfermented bacterial infection in lower respiratory tract from January to December in 2007 in Xiangya Hospital were analyzed retrospectively. The distribution and drug sensitivity of pathogens were recorded. Of those 229 patients,183 cases were infected by non-fermented multi-drug resistant bacteria( MDRB) . The risk factors for non-fermented MDRB infection in lower respiratory tract were analyzed by multi-factor logistic multiple regression analysis.Results The top four non-fermented bacteria isolated were Pseudomonas aeruginosa( 47.6%) , Acinetobacter baumannii( 36. 3% ) , Acinetobacter spp( 8. 6% ) , and Stenotrophomonas maltophilia( 5. 1%) . Higher isolatated rate was found in neurosurgery ( 25. 7% ) and central ICU( 22. 9% ) . The isolated non-fermented bacteria except Stenotrophomonas maltophilia were resistant to all antibiotics except cefoperazone-sulbactam and meropenem. ICU stay( P lt; 0. 001) , tracheotomy or tracheal intubation( P = 0. 001) , and previous use of carbapenemantibiotics( P =0. 032) were independent risk factors for non-fermented MDRB infection. Conclusion Non-fermented bacillus were important pathogens of nosocomial infection in lower respiratory tract with high rates of antibiotic resistance. It is important to prevent non-fermented MDRB infection by strict limitation on the indication of ICU stay,tracheotomy and use of carbapenem.
ObjectiveTo evaluate the effect of neoadjuvant chemotherapy and find the mechanism of multidrug resistance. MethodsTwenty patients with gastric cancer and 31 patients with colorectal cancer underwent neoadjuvant chemotherapy and then operations. The preoperative specimens were stained by immunohistochemical techniques for testing p53,multidrug resistanceassociated protein (MRP), glutathione S transferase（GST）, telomerase. Resection specimens were evaluated for chemotherapy effect by routine histology; at the same time, the postoperative morbidity and mortality were observed. ResultsIn 51 patients, the response rate of neoadjuvant chemotherapy was 27.45%(14/51),so multidrug resistance was a kind of common phenomena in gastrointestinal carcinomas. The postoperative morbidity was 15.69%(8/15), the main operation complication was infection,the mortality was 1.96%(1/51),only one person died from severe infection.The expression rate of p53, MRP, GST, telomerase was 58.0%,51.0%,66.7%,74.0%respectively, the location of p53 was at cell nucleus,location of MRP,GST was at cell memberane and cytoplasm,location of telomerase was at cytoplasm.The response rate had nothing to do with age, sex and metastasis. But it was related with p53 and telomerase expression. ConclusionNeoadjuvant chemotherapy is an effective, safe therapy. But the rate of drug resistance is high in gastrointestinal carcinomas, and the response rate is related to p53, telomerase expression.
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.
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.
ObjectiveTo elucidate the latest research progress of Yes-associated protein (YAP) / transcriptional coactivator with PDZ-binding motif (TAZ) in regulating tumor drug resistance. MethodThe relevant literature on YAP/TAZ in regulating tumor cell chemotherapy, immunotherapy, and targeted therapy resistance was reviewed and summarized in the databases such as PubMed, CNKI, and so on. ResultsThe YAP/TAZ was involved in the resistance regulation of chemotherapy, immunotherapy, and targeted therapy in various human tumors. The YAP/TAZ could interact with various proteins to induce the occurrence of tumor resistance. The imbalance of YAP/TAZ signaling might lead to an important mechanism of tumor cell resistance. ConclusionsThere is a close relation between YAP/TAZ and tumor cell resistance. Studying the mechanism of YAP/TAZ regulating tumor resistance can provide new strategies and targets for addressing tumor resistance.
Objective To investigate the clinical characteristics and drug resistance changes of nosocomial infection caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) in different types of clinical departments, and to provide evidence for prevention and control of CRKP infection. Methods The hospital infection real-time monitoring system was used to retrospectively collect the inpatients with CRKP nosocomial infection in the First People’s Hospital of Lianyungang from January 2019 to December 2023 as the research objects. According to the different sources of departments, they were divided into intensive care unit (ICU) group, internal medicine group and surgery group. The changes of clinical characteristics and drug resistance to common antibiotics were analyzed. Results A total of 636188 inpatients were monitored, and 225 cases were infected with CRKP, with an overall infection detection rate of 0.035%. The detection rates of CRKP infection in the ICU group, internal medicine group, and surgery group were 0.736% (138/18749), 0.013% (44/336777), and 0.015% (43/280662), respectively, with the ICU group demonstrating a significantly higher rate than the other groups (P<0.05). The detection rates fluctuated in the early stage and then decreased rapidly in different years. The main infection site of CRKP in all groups was lower respiratory tract, but the proportion of device-related infections in the ICU group was higher than that in the internal medicine and surgery groups (P<0.05). In terms of the infected population, there was no significant difference in gender among groups (P>0.05) with the proportion of males more than 60%, while the difference in the proportion of patients aged ≥65 years among groups was statistically significant (P<0.05), with the highest in the internal medicine group (86.36%). The burden of underlying diseases and invasive operation exposure of the infected patients were high, and the proportion of cardiovascular and cerebrovascular diseases and indwelling catheters were as high as 69.33% and 83.56%, respectively. The differences in the proportions of cardiovascular and cerebrovascular diseases, diabetes mellitus, ≥3 underlying diseases, and surgical and invasive procedures among groups were statistically significant (P<0.05). The distribution of infection specimens in each group showed no statistically significant difference (P>0.05), with sputum, blood, and mid-stream urine specimens being the main detected specimens in all groups. The resistance rates of CRKP to penicillins and cephalosporins were more than 93%, and the resistance rates to aminoglycosides and sulfonamides were relatively low and showed a decline year by year. The resistance rate to ceftazidime/avibactam was only 7.41%, but the resistance rate to tigecycline increased. The difference in resistance rate of CRKP to co-trimoxazole among groups was statistically significant (P<0.05), while the differences in resistance to other antimicrobial agents were not statistically significant (P>0.05). Conclusions The detection rate, clinical characteristics and drug resistance of CRKP infection in different types of departments of medical institutions are different and changing. It is necessary to strengthen the rational use of antibiotics and the prevention and control of nosocomial infection.