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Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.
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Male , Humans , Prostate-Specific Antigen , Treatment Outcome , Prostatic Neoplasms, Castration-Resistant/drug therapy , Immune Checkpoint Inhibitors/therapeutic use , Retrospective StudiesABSTRACT
Objective To establish a method for the determination of total polyphenols and catechins in betel nut polyphenols extract, and provide reference for the quality control of betel nut polyphenols extract. Methods The content of total phenol in betel nut extract was determined by ultraviolet spectrophotometry. The content of catechins was determined by HPLC. Results The linear range of total polyphenols in betel nuts extract was 9.8~58.8 μg/ml. The three components of catechin, epicatechin and protocatechuic acid were completely separated by HPLC, and the linear relationship was good in their respective ranges, with the recoveries between 99.17% and 101.67%, the RSD between 1.2% and 2.5%. Conclusion The established method is simple, stable and reliable, which could be used for the quantitative analysis of betel polyphenol extract, and provide experimental basis for the quality control of betel polyphenol extract.
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Breast cancer is one of the most malignant tumors and is associated with high mortality rates among women. Lycium barbarum polysaccharide (LBP) is an extract from the fruits of the traditional Chinese herb, L. barbarum. LBP is a promising anticancer drug, due to its high activity and low toxicity. Although it has anticancer properties, its mechanisms of action have not been fully established. Ferroptosis, which is a novel anticancer strategy, is a cell death mechanism that relies on iron-dependent lipid reactive oxygen species (ROS) accumulation. In this study, human breast cancer cells (Michigan Cancer Foundation-7 (MCF-7) and MD Anderson-Metastatic Breast-231 (MDA-MB-231)) were treated with LBP. LBP inhibited their viability and proliferation in association with high levels of ferroptosis. Therefore, we aimed to ascertain whether LBP reduced cell viability through ferroptosis. We found that the structure and function of mitochondria, lipid peroxidation, and expression of solute carrier family 7 member 11 (SLC7A11, also known as xCT, the light-chain subunit of cystine/glutamate antiporter system Xc-) and glutathione peroxidase 4 (GPX4) were altered by LBP. Moreover, the ferroptosis inhibitor, Ferrostatin-1 (Fer-1), rescued LBP-induced ferroptosis-associated events including reduced cell viability and glutathione (GSH) production, accumulation of intracellular free divalent iron ions and malondialdehyde (MDA), and down-regulation of the expression of xCT and GPX4. Erastin (xCT inhibitor) and RSL3 (GPX4 inhibitor) inhibited the expression of xCT and GPX4, respectively, which was lower after the co-treatment of LBP with Erastin and RSL3. These results suggest that LBP effectively prevents breast cancer cell proliferation and promotes ferroptosis via the xCT/GPX4 pathway. Therefore, LBP exhibits novel anticancer properties by triggering ferroptosis, and may be a potential therapeutic option for breast cancer.
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Female , Humans , Breast Neoplasms/drug therapy , Drugs, Chinese Herbal/pharmacology , Ferroptosis , Glutathione/metabolism , Iron/metabolismABSTRACT
Areca catechu L. medicinal materials and their preparations are widely used in clinical practice. Betelnut polyphenol is one of the main chemical components with antioxidant, anti-inflammatory, and antibacterial effects. With continuous increase of high altitude activities, tissue oxidative damage caused by high altitude hypoxia seriously affects the ability to work, and the studies on anti-hypoxia drugs are particularly important. Recent studies have shown that betelnut polyphenols have protective effects on oxidative stress injury caused by hypoxia via improving blood gas index of hypoxic organism, increasing superoxide dismutase glutathione catalase activity, and scavenging excessive free radicals. The effects of betelnut polyphenols against hypoxia and oxidative damage protection suggest that betelnut polyphenols can be used as potential anti-hypoxia drugs and posses clinical prospects.
Subject(s)
Humans , Antioxidants/pharmacology , Areca/chemistry , Hypoxia , Oxidative Stress , Polyphenols/pharmacology , Superoxide Dismutase/metabolismABSTRACT
Objective: To compare the short-term effectiveness of one-stage posterior debridement with non-structural bone graft and structural bone graft in the treatment of single segment thoracic tuberculosis. Methods: The data of 61 patients with single segment thoracic tuberculosis, who were treated by one-stage posterior debridement, bone graft fusion, and internal fixation between June 2011 and August 2015, was retrospectively analyzed. All of them, 26 cases were treated with structural bone graft (group A) and 35 cases with non-structural bone graft (group B). No significant difference was found between the two groups in gender, age, disease duration, comorbidity, involved segments, paravertebral abscess, and preoperative American Spinal Injury Association (ASIA) grade, C reactive protein (CRP), visual analogue scale (VAS) score, and Cobb angle of involved segments ( P>0.05). But the preoperative erythrocyte sedimentation rate (ESR) in group B was significantly lower than that in group A ( t=3.128, P=0.003). The operation time, intraoperative blood loss, hospitalization stay, VAS score, ESR, CRP, ASIA grade, postoperative complications, Cobb angle of involved segments and its correction rate and loss rate, and bone fusion time were recorded and compared between the two groups. Results: Compared with group A, group B had shorter operation time, less intraoperative blood loss, and longer hospitalization stay, showing significant differences ( P0.05). At last follow-up, the ASIA grade of the two groups significantly improved when compared with those before operation, and there was no significant difference between the two groups ( Z=-1.104, P=0.270). There were 9 cases and 10 cases of complications in groups A and B, respectively, and there was no significant difference ( χ2=0.254, P=0.614). The Cobb angle in group B was significantly higher than that in group A at 3 days after operation ( t=-2.861, P=0.006), but there was no significant difference in Cobb angle between the two groups at last follow-up ( t=-1.212, P=0.230). The postoperative correction rate and loss rate of Cobb angle in group A were higher than those in group B, and there was a significant difference in the loss rate between the two groups ( t=2.261, P=0.031). All patients got bone graft fusion and the bone fusion time of group B was significantly shorter than that of group A ( t=4.824, P=0.000). Conclusion: Non-structural and structural bone graft can both achieve good effectiveness in the treatment of single segment thoracic tuberculosis, but the former has the advantages of less surgical trauma and shorter fusion time.
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Objective To analyze the characteristics ofgastroesophageal reflux disease (GERD) under general gastroscope.Methods The detection rates of GERD related abnormalities such as esophagitis,Barrett esophagus and hiatal hernia under the first gastroscopy of the adult GERD patients from January 2013 to January 2017 in our center and the statistical relationship between the abnormal findings were analyzed retrospectively.Results A total of 4086 GERD patients,2004 males and 2082 females,were included in this study,and the age was 18-89(50.4 ± 13.3) years old.The detection rate of non erosive GERD was 78.7％,esophagitis 21.3％;non Barrett esophagus 87.7％,suspected Barrett esophagus 8.3％,Barrett esophagus 3.9％;generally normal cardia 61.4％,short segment hiatus hernia 20.4％,and long segment hiatal hernia 18.2％.The detection rates of esophagitis showed statistically significant differences (P＜0.001) between the three groups of generally normal cardia,short segment hiatal hernia and long segment hiatal hernia;The detection rate of Barrett esophagus was significantly higher in long segment hiatal hernia group than in generally normal cardia group and short segment hiatal hernia group (P＜0.001,P=0.012),but the difference between the later two groups was not statistically significant (P＞0.013).Comparing the three age groups of 18-39,40-59 and ≥60 years old,the detection rate of hiatal hernia was significantly higher in the group of≥60 years old than in the 18-39 and 40-59 years old groups (P=0.007),while there was no significant difference (P＞0.013) between the 18-39 and 40-59 years old groups.The detection rate of esophagitis was significantly higher in ≥60 years old group than in 18-39 and 40-59 years old groups (P=0.004,P=0.008),while no significant statistically difference (P＞0.013) was found between the later two groups.Conclusions Gastroscopy can be used as a basic examination means for GERD;short segment hiatal hernia can be regarded as an early form of hiatal hernia,and is of important reference value for the diagnosis and treatment of GERD;more serious hiatal hernia and esophagitis could be found in elderly GERD patients.
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To observe the clinical efficacy of modified Chaiping decoction for HBeAg-negative chronic hepatitis B under DaBianZheng theory(syndrome differentiation theory) guidance with understanding of purgative detoxing and modern pharmacology research of traditional Chinese medicine. The patients with HBeAg-negative chronic hepatitis B(n=119) were randomly divided into treatment group(n=69) and control group(n=50). The patients in treatment group were treated with the modified Chaiping decoction(6 doses per week, one dose every day in two times by oral administration), and the patients in control group were treated with lamivudine(LAM) (100 mg/time, once a day). All of patients were treated for 48 weeks. The liver functions, levels of DNA of hepatitis B virus (HBV-DNA) and clinical symptoms were observed at weeks 12, 24, 36 and 48 in both groups. The levels of ALT and HBV-DNA in serum were also observed 24 weeks and 48 weeks after treatment in two groups. There was no significant difference in total effective rate between treatment group and control group at week 24, but the total effective rate in treatment group was higher than that in the control group at weeks 12, 36 and 48(P<0.05); the improvement of liver functions in the treatment group was superior than that in the control group at weeks 12, 36 weeks and 48(P<0.01 or P<0.05), but there was no significant difference at week 24; the improvement of serum HBV-DNA in the treatment group was significantly lower than that in the control group at week 12(P<0.01), but there was no significant difference at weeks 24, 36 and 48; the negative converse rate of serum HBV-DNA in the treatment group was lower than that in the control group at weeks 12, 24 and 36(P<0.01 or P<0.05), but there was no significant difference at week 48; the improvement of fatigue, lassitude, abdominal distension and hypochondriac pain in treatment group was significantly better than that in the control group at weeks 12 and 24(P<0.01 or P<0.05), but there was no significant difference in the improvement of fatigue and hypochondriac pain at weeks 36 and 48; the abnormal rate of ALT in treatment group was significantly lower than that in the control group 24 weeks and 48 weeks after drug withdrawal(P<0.01); there was no significant difference in abnormal rate of serum HBV-DNA 24 weeks after drug withdrawal, but it was significantly lower than that in the control group 48 weeks after drug withdrawal(P<0.05). Modified Chaiping decoction with combination of long term medication and intermittent administration showed better clinical efficacy on HBeAg-negative chronic hepatitis B. Its prescription compositions shall be further optimized and consummated under guidance of disease differentiation and syndrome differentiation, and its clinical research on hepatic fibrosis and living quality shall be carried out.
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[Summary] This paper was to investigate whether serum angiopoietin-like protein 2 (Angptl 2) is associated with macrovascular complications in type 2 diabetes mellitus.The results showed that there were statistically significant differences in serum Angptl 2 levels among control group and groups of type 2 diabetic patients with or without carotid atherosclerosis [0.98 (0.82-1.22),3.70 (2.69-4.85),1.17 (0.76-2.47) ng/ml].Logistic regression showed that Angptl 2 was an independent risk factor of macrovascular complications in the patients with type 2 diabetes.
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Phacoemulsification cataract extraction and intraocular lens (IOL) implantation has become the mainstream treatment of cataract.But the postoperative residual astigmatism still influences the postoperative uncorrected visual acuity.Reduce residual astigmatism is currently the ophthalmologists' pursuit.The formation of the residual astigmatism is affected by various factors,which mainly associated with preoperative corneal astigmatism and surgically induced astigmatism.Except for the above reasons,residual astigmatism after Toric IOL implantation has its special reasons.Understanding the reasons of formation of residual astigmatism can provide us the methods how to reduce it.This paper reviewed the causes of the residual astigmatism after phacoemulsification cataract extraction and IOL implantation.
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Objectives To address whether menopause affects outcome of catheter ablation (CA) for atrial fibrillation (AF) by comparing the safety and long-term outcome of a single-procedure in pre-and post-menopausal women. Methods A total of 743 female patients who underwent a single CA procedure of drug-refractory AF were retrospectively analyzed. The differences in clinical presentation and outcomes of CA for AF between the pre-menopausal women (PreM group, 94 patients, 12.7%) and the post-menopausal women (PostM group, 649 patients, 87.3%) were assessed. Results The patients in the PreM group were younger (P<0.001) and less likely to have hypertension (P<0.001) and diabetes (P=0.005) than those in the PostM group. The two groups were similar with regards to the proportion of concomitant mitral valve regurgitation coronary artery disease, left atrium dimensions, and left ventricular ejection fraction. The overall rate of complica-tions related to AF ablation was similar in both groups (P=0.385). After 43 (16-108) months of follow-up, the success rate of ablation was 54.3%in the PreM group and 54.2%in the PostM group (P=0.842). The overall freedom from atrial tachyarrhythmia recurrence was simi-lar in both groups. Menopause was not found to be an independent predictive factor of the recurrence of atrial tachyarrhythmia. Conclusions The long-term outcomes of single-procedure CA for AF are similar in pre-and post-menopausal women. Results indicated that CA of AF appears to be as safe and effective in pre-menopausal women as in post-menopausal women.
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Background The rapid diagnosis can win more treating opportunities for patients with fungal keratitis.Even though the fungal culture is the gold standard for the diagnosis of fungal keratitis,it is difficult in early diagnosis due to the long duration of cultivation and false-negative rate.Objective This trial was to explore the clinical value in the rapid diagnosis of fungal keratitis by the combination of corneal scraping with laser scanning confocal microscopy.Methods Corneal scraping and laser scanning confocal microscopy were separately performed in 167 eyes of 167 patients with fungal keratitis.All the eyes were examined by the slit lamp,followed by laser scanning confocal microscope,and then the 10％ KOH corneal smear was examined under the optical microscope.Results The positive rate of diagnosis was 75％ (125/167) by corneal scraping,and that by laser scanning confocal microscopy was 91％ (152/167).The positive rate of examining outcome was significantly higher in laser scanning confocal microscopy than that of corneal scraping (x2 =14.88,P =0.00).The positive results were 114 cases and negative results were 4 cases by two methods,with the concordance rate 70.7％ (118/167).The hyphae or spore were seen in 32 cases by laser scanning confocal microscopy in 42 negative cases by corneal scraping,and in 15 negative cases by confocal laser scanning microscopy,11 positive outcomes were offered by corneal scraping.Conclusions The combined application of corneal scraping with confocal laser scanning microscopy can improve and speed up the diagnosis positive rate of fungal keratitis.
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<p><b>OBJECTIVE</b>To elucidate the antifibrotic mechanism of Huangqi decoction in rats with BDL-induced cholestatic liver fibrosis.</p><p><b>METHODS</b>Liver fibrosis model was induced by ligating the common bile duct (BDL) in rats. Sham-operation was performed in control rats. The BDL rats were randomly divided into two groups: the BDL group and the Huangqi decoction group. Huanqi decoction was given intragastrically for 4 weeks. At the end of the fifth week after BDL, animals were sacrificed.</p><p><b>RESULTS</b>Compared with the sham control group, mortality rate in BDL group was 33.3% and incidence rate of ascites was 90%, and hepatic function was abnormal in most of the rats in BDL group. The number of Hepatocytes was decreased and the number of cholangiocytes significantly increased in BDL group. In addition, Hyp content of liver tissue and protein expression of CK 7 and a-SMA were significantly increased. Immunostaining indicated that CK 7 and a-SMA were co-localized in BDL group. These changes were markedly suppressed by the Huangqi decoction.</p><p><b>CONCLUSIONS</b>These observations suggest that Huangqi decoction can inhibit cholangiocyte proliferation and cholangiocyte transdifferentiation.</p>
Subject(s)
Animals , Male , Rats , Actins , Metabolism , Astragalus Plant , Bile Ducts , Pathology , Cell Proliferation , Cell Transdifferentiation , Disease Models, Animal , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Epithelial Cells , Hyaluronic Acid , Metabolism , Keratin-7 , Metabolism , Liver , Metabolism , Pathology , Liver Cirrhosis, Biliary , Drug Therapy , Metabolism , Pathology , Liver Function Tests , Plants, Medicinal , Chemistry , Rats, Sprague-DawleyABSTRACT
<p><b>OBJECTIVE</b>To investigate the mechanism of hepatocytes transdifferentiation to bile duct epithelial cells (BECs) and intervention of Huangqi decoction (HQD) on hepatic fibrosis formation in rats with secondary cholestasis.</p><p><b>METHODS</b>Seventy-five SD male rats were made into cholestatic hepatic fibrosis model animals by bile duct ligation, and randomized into the control group (n = 50) and the HQD group (n = 15). Starting from one week after modeling, they were administered orally with saline and HQD respectively for four weeks. Besides, a sham-operated group was set up with 10 rats operated by choledochus segregating only and administered after then with saline. Rats were killed in batches at different time points, i.e. each five from the control group and sham-operated group at the end of the 1st week, five from the control group for each time at the end of the 2nd, 3rd and 4th week, and all the remaining rats at the end of the 5th week. Their liver tissues were taken for histological change examination, content of hydroxyproline (Hyp) determination; protein expression of BECs marker cytokeratin 7 (CK7) and the hepatocyte specific antigen HepPar detection by Western blot, and CK7-Hep Par co-localization by laser confocal microscopy. Then IPP software was used to analyze Sirius red stained positive areas of CK7 and Hep Par, as well as the average IOD of CK7/Hep Par co-localization.</p><p><b>RESULTS</b>Hepatocytes in hepatic tissues (Hep Par positive cell) in the model rats decreased gradually along was time went by after modeling (Sham > M1w > M2w > M3w > M4w > M5w), which was in parallel with the increase of BECs (CK7 positive cells), degree of fibrosis, Hyp content and CK7 protein expression. Increasing of co-localized positive cells of CK7/Hep Par began at 1 week and reached the peak 3 weeks after modeling, then it decreased gradually. The Hep Par protein expression was negatively correlated with that of CK7; the Hep Par positive cell expression was negatively correlated with CK7 positive cell expression and collagen deposition; while the CK7 positive cell expression was positively correlated with the collagen deposition in the liver tissue. Compared with the model control group, the mortality, CK7/Hep Par co-localized positive cells, fibrosis degree, Hyp content and CK7 protein expression were lesser obviously (P < 0.01), while Hep Par positive cell and protein expressions were higher significantly in the HQD group.</p><p><b>CONCLUSIONS</b>Hepatocytes transdifferentiation to BECs might be a key pathological element for secondary cholestatic hepatic fibrosis formation; the restraining action of HQD is possibly a major action mechanism of HQD for effectively intervening and treating secondary cholestasis hepatic fibrosis.</p>
Subject(s)
Animals , Male , Rats , Astragalus Plant , Bile Ducts , Cell Biology , Cell Transdifferentiation , Drugs, Chinese Herbal , Pharmacology , Epithelial Cells , Cell Biology , Hepatocytes , Cell Biology , Liver , Liver Cirrhosis, Biliary , Drug Therapy , Pathology , Phytotherapy , Rats, Sprague-DawleyABSTRACT
Objective To investigate the prevalence of 16S rRNA methylases gene in imipenem-resistant Acinetobacter baumannii isolates from China. Methods A total of 342 imipenem-resistant A.baumannii isolates were collected between December 2004 and December 2005, from 25 hospitals of China. Agar dilution was used to determinate the minimal inhibitory concentration (MIC) of these isolates. The homology of these isolates was analyzed by pulse-field gel electrophoresis (PFGE). Several 16S rRNA methylase genes and carbapenemase genes were detected by PCR-based assays and PCR products were sequenced. Results The rates of resistance to ampicillin-sulbactam, cefoperazone-sulbactam, tobramycin, and minocycline were 68.0%, 54.2%, 87.4%, and 75.9%, respectively. The rate of resistance to polymyxin E was 10.8%, the lowest among the tested agents. The rates of resistance to all other tested antimicrobial agents were more than 90%. The A.baumannii isolates belonged to 29 distinct clones. Among them, 6 clones were dominant, consisting of 303 isolates in total. All isolates contained the blaOXA-51-1ike gene (blaOXA-66) and 322 isolates contained the blaOXA-23-1ike gene. PCR with the ISAbal-OXA-23-like primers generated a PCR product in 314 isolates, and PCR with the ISAbal-OXA-51-1ike primers generated a PCR product in 13 strains. 221 armA-positive isolates were identified. Conclusion Most of the imipenem-resistant A.baumannii contained blaOXA-23, with ISAbal upstream of the gene. 16S rRNA methylase gene armA was widely distributed in these isolates. The results suggested that the spread of clones played an important role in the outbreak of imipenem-resistant A. baumannii in China.
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Objective To characterize the antibiotic resistance,homology and carbapenemase genotypes of imipenem resistant Acinetobac1ter baumannii isolated from our hospital,and analyze the clonal relatedness of the test strains.Methods Ninety five strains of imipenem resistant A.baumannii were isolated from August 2003 to December 2004 in the First Affiliated Hospital, College of Medicine,Zhejiang University.The MICs of 16 antimicrobial agents against these strains were determined by agar dilution and E-test method.The homology of these isolates was analyzed by pulse-field gel electrophoresis(PFGE).The coding gene of carbapenemases was amplified.PCR products were purified,cloned and sequenced.Plasmid DNA was extracted and purified.Conjugation and Southern blot were performed to locate the position of oxa 23 gene.Results The resistance rates to ampicillin-sulbactam and cefoperazone sulhactam were 67.9% and 30.2%.Polymyxin E had the lowest resistance rate of 17%. The resistance rate to other antimicrobial agents was higher than 90%.The 95 strains,isolated from 10 clinical units,were classified into 6 clones.Clones A and B were predominant clones.All strains produced carbapenemases which were confirmed as OXA 23 by PCR and sequencing analysis.No plasmid was extracted and conjugation was not successful.Southern bolt showed that oxa-23 gene was located on Apal-digested chromosomal segments about 220 kb and 200 kb in Clones A and B,re spectively.Conclusions OXA 23-producing A.baumannii has become one of the most important multi-resistant pathogens in our hospital.Clones A and B have widely spread in our hospital.Oxa-23 gene is located on chromosomal DNA.
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Objective To observe the effects of cell cycle inhibitor on astrocytic proliferation and scar formation and to study neuronal apoptosis after focal cerebral ischemia in rats.Methods Ischemic model was established by photochemistry method.T_2-weighted MRI was performed on the 3rd, 7th, and 30th day after focal cerebral ischemia.The expression of glial fibrillary acidic protein(GFAP)and apoptosis was observed by immunofluorescence.The protein levels of GFAP and proliferation cell nuclear antigen (PCNA), CyelinA and CyclinB1 were measured by Western blotting from the ischemic and sham animals finished on the 3rd, 7th, and 30th day.Results A marked and significant reduction of brain infarction volume was found in Olomoucine-treated ischemic animals(2.27%?0.28% , 1.87%?0.19%, 1.08%? 0.18%)as compared with controls(5.10%?0.35%, 4.60%?0.26%, 3.96%?0.28%, P
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Objective To investigate the resistant mechanism of imipenem-resistant K. pneumoniae.Methods The minimal inhibitive concentrations (MICs) of the antimicrobial agents were determined by Etest.Isoelectric focusing electrophoresis (IEF),plasmid extraction,conjugation, transformation,PCR amplification,cloning and sequencing were carried out for analyzing the encoding gene of ?-1actamases.Results Three kinds of ?-1actamases were detected with pIs of 7.2,6.7,and 5.4.in a clinical strain of K.pneumoniae.These ?-1actamases were TEM-I (pI,5.4),SHV-12 (pI,8.2) and KPC-2 ( pI,6.7 ) confirmed by sequencing of the PCR products.Only one band of ?-1actamase with pI 6.7 was displayed in the transformant.A 1500 bp segment,which contained the KPC-2 gene confirmed by nucleotide sequence analysis,was cloned from a 60 000 bp plasmid of the transformant.Conclusion The strain of K.pneumoniae resistant to imipenem produces a plasmid-mediated carbapenemase KPC-2 which belongs to Bush group 2f,class A ?-1actamase.