1.Total PSA, PSA density and biopsy Gleason score in predicting the pathologic stage of prostate cancer.
Shuai LIU ; Jia-ju LÜ ; Qiang FU ; Hui ZHANG ; De-xuan GAO ; Zheng LIU
National Journal of Andrology 2010;16(5):415-419
OBJECTIVETo evaluate the roles of total prostate specific antigen (tPSA), PSA density (PSAD) and biopsy Gleason score in predicting the pathologic stage of prostate cancer.
METHODSWe retrospectively analyzed the clinical data of 124 cases of pathologically confirmed prostate adenocarcinoma, and divided them into Groups A (n=48) and B (n=76) based on the results of bone scanning, CT, MRI, tPSA, PSAD and postoperative biopsy Gleason score, the former with extraprostatic infiltration or distant metastasis, while the latter without. We compared the above parameters between the two groups, screened the main factors that influenced the pathologic staging of prostate cancer by multivariate logistic regression analysis, and appraised the value of each of the parameters in predicting the pathologic stage of prostate cancer with a relative operating characteristic (ROC) curve.
RESULTSThe tPSA level and biopsy Gleason score were significantly higher in Group A than in B (P < 0.05). Multivariate logistic regression analysis showed that only tPSA could predict the pathologic stage of localized prostate cancer. The ROC curve exhibited that the combined use of tPSA and Gleason score had a better predicting value than other parameters (Gleason score + tPSA > tPSA > PSAD + tPSA + Gleason score).
CONCLUSIONTotal PSA remains a valuable predictor of the pathologic stage of prostate cancer, and its combination with Gleason score can further improve the predictive accuracy and contribute much to the treatment and prognosis of the disease.
Adenocarcinoma ; blood ; pathology ; Adult ; Aged ; Aged, 80 and over ; Biopsy ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Postoperative Period ; Prognosis ; Prostate ; pathology ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms ; blood ; pathology ; Retrospective Studies
2.Application of ultrasonic microscopy in biomechanical properties measurement of cancellous bone.
Zhi-yong YU ; Yun GAO ; Wan-qiang ZHANG ; De-long WANG ; Xuan WANG
China Journal of Orthopaedics and Traumatology 2008;21(7):523-524
OBJECTIVEUltrasound scanning can provide the information of acoustic impedance through the ultrasonic reflection theory. This study tries to introduce the application of the ultrasonic technique in predicting biomechanical properties of cancellous bone.
METHODSThe rat femoral head embedded in plexiglass was used as the bone specimens for ultrasound scanning and the gray scale images scanned by ultrasound microscope were collected and analyzed.
RESULTSThe value of acoustic impedance was calculated by analyzing the gray scale image.
CONCLUSIONThe application of ultrasonic microscopy can show more value about the microstructure of biomechanical properties of bone tissue.
Animals ; Biomechanical Phenomena ; Bone Density ; Femur Head ; diagnostic imaging ; physiology ; Microscopy, Acoustic ; methods ; Osteoporosis ; physiopathology ; Rats
3.Repair of the soft tissue defects at legs with free tissue flap anastomosed with descendant branch of lateral femoral circumflex artery.
Shun-hong GAO ; Chao CHEN ; Cheng JIAO ; Xiao-xuan FEI ; Lai-qing SUN ; Wen-long ZHANG ; Hui-shuang DONG ; Bin WANG ; Hui-ren LIU ; De-qun LIU
Chinese Journal of Plastic Surgery 2011;27(3):201-203
OBJECTIVETo investigate the therapeutic effect of free tissue flap anastomosed with reverse descendant branch of lateral femoral circumflex artery for severe soft tissue defect at leg.
METHODSThe severe soft tissue defect at leg, without any vessels for anastomosis of free tissue flap, was reconstructed with free tissue flap, which was anastomosed with proximal end of descendant branch of lateral femoral circumflex artery and great saphenous vein. From Oct. 2004 to Dec. 2009, 36 cases were treated with 15 cases of latissimus dorsi musculocutaneous flaps, 12 cases of anterolateral femoral flaps, and 9 cases of thoracoumbilicus flaps.
RESULTSAll the 36 free flaps survived completely. The patients were followed up for 6 months to 2.5 years with good cosmetic results.
CONCLUSIONSIt is effective and practical to repair the severe soft tissue defects at legs with the reverse descendant branch of lateral femoral circumflex artery to carry the free flaps.
Adult ; Female ; Femoral Artery ; surgery ; Follow-Up Studies ; Free Tissue Flaps ; Humans ; Leg Injuries ; surgery ; Male ; Middle Aged ; Skin Transplantation ; methods ; Soft Tissue Injuries ; surgery ; Thigh ; surgery ; Treatment Outcome ; Young Adult
4.An analysis for the phenotype and genotype of autosomal dominant polycystic kidney disease from two Chinese families.
De-xuan GAO ; Qing-wei CAO ; Ke-jia DING ; Yue-ran ZHAO ; Lai-cheng WANG ; Zhi-hong NIU ; Jia-ju LU
Chinese Journal of Medical Genetics 2006;23(1):23-26
OBJECTIVETo scan for mutations of polycystic kidney disease 1 gene (PKD1) in Chinese population in order to find some features about Chinese patients and a better approach to detect mutations.
METHODSTwenty-five PKD-affected individuals from twenty-one unrelated genealogies and sixteen controls participated in the study. Thirty-five blood samples and six tissues were obtained after receiving informed consent and were in accordance with institutional ethical guidelines. Genomic DNA was isolated from peripheral blood using standard procedures. PCR amplification of genomic DNA was performed to generate the aimed fragments. Amplified fragments were analyzed by denaturing gradient gel electrophoresis (DGGE). A GC clamp was attached to the 5' primer. After that, the abnormal fragments were sequenced on freshly amplified specific PCR products with the dideoxynucleotide chain termination method. Sequencing was performed for all samples to evaluate DGGE.
RESULTSAimed fragments of exons 44 and 45 were amplified. DGGE detected eleven abnormal PCR fragments. Two novel mutations were identified by sequencing, included one nonsense mutation (C12217T) and one frameshift (12431delCT). In addition, one polymorphism (A50747C) was identified. The mutation detection rate is 8% in our study.
CONCLUSIONTwo novel pathogenic mutations were detected, including one nonsense mutation (C12217T) and one frameshift (12431delCT).
Asian Continental Ancestry Group ; genetics ; Codon, Nonsense ; DNA Mutational Analysis ; Exons ; genetics ; Family Health ; Female ; Frameshift Mutation ; Genotype ; Humans ; Male ; Middle Aged ; Mutation ; Pedigree ; Phenotype ; Polycystic Kidney, Autosomal Dominant ; genetics ; Polymorphism, Single Nucleotide ; Proteins ; genetics ; TRPP Cation Channels
5.Expression of Ang2 and Tie2 and their relation with the angiogenesis of hepatocellular carcinoma in rats.
Wen-zheng LI ; Pu YANG ; Guang-chun PENG ; Hui-huan TANG ; Jun ZHOU ; Chun-yan FU ; De-yun FENG ; Xuan ZHOU ; Man-ping HUANG ; Gao-feng ZHOU
Journal of Central South University(Medical Sciences) 2006;31(4):523-527
OBJECTIVE:
To investigate the relationship between the expression of Ang2, Tie2 and the angiogenesis of hepatocellular carcinoma in rats.
METHODS:
Thirty-eight healthy male rats were randomly divided into 3 groups: 5 rats in the control group; 25 rats in the experimental group were equally divided into 5-day, 10-day, 15-day, 20-day, and 25-day groups; the other 8 rats were used as the supplement of the experimental group. An allogenic transplanted rat model of CBRH-7919 hepatocellular carcinoma in situ was established by immunosuppression. The expressions of Ang2 and Tie2 were detected by immunohistochemical staining in cancerous tissues of different developmental stages and liver tissues of the control group. At the same time, microvessel density was determined by anti-CD31 immunohistochemical staining.
RESULTS:
CBRH-7919 hepatocellular carcinoma models were successfully set up in 24 rats. The expression level of Ang2 and Tie2 in cancerous tissues was much higher than that of liver tissues of the control group (P <0.05). The overexpression of Ang2 was pristine and continuous in different developmental stages. The expressions of Ang2 and Tie2 positively correlated with microvessal density in hepatocellular carcinoma (P<0.05).
CONCLUSION
The up-regulation of Ang2 and Tie2 may play important roles in the angiogenesis of hepatocellular carcinoma. Ang2 may participate in the start of angiogenesis of hepatocellular carcinoma.
Angiopoietin-2
;
biosynthesis
;
genetics
;
Animals
;
Liver Neoplasms, Experimental
;
blood supply
;
metabolism
;
Male
;
Neovascularization, Pathologic
;
RNA, Messenger
;
genetics
;
Random Allocation
;
Rats
;
Rats, Wistar
;
Receptor, TIE-2
;
biosynthesis
;
genetics
6.Tumor-infiltrating regulatory T cells are positively correlated with angiogenic status in renal cell carcinoma.
Hao NING ; Qian-Qian SHAO ; Ke-Jia DING ; De-Xuan GAO ; Qing-le LU ; Qing-Wei CAO ; Zhi-Hong NIU ; Qiang FU ; Chun-Huan ZHANG ; Xun QU ; Jia-Ju LÜ
Chinese Medical Journal 2012;125(12):2120-2125
BACKGROUNDImmune cells within a tumor microenvironment have shown modulatory effects on tumor angiogenic activity. Renal cell carcinoma (RCC) is a hypervascular tumor that reportedly increases the frequency of regulatory T cells (Tregs) in tumor tissues. This study investigated the correlation between Tregs infiltration and angiogenic status in RCC.
METHODSThirty-six patients with RCC were enrolled in the present study, and twenty age-matched healthy donors were included as the control. Tregs were defined as CD4(+)CD25(high)CD127(low/-) T cells. The frequency of Tregs in peripheral blood and tumor infiltrating lymphocytes (TILs) were determined by flow cytometry. The expression of vascular endothelial growth factor (VEGF) in surgical resection specimens were measured with a commercial enzyme-linked immunosorbent assay (ELISA) kit. Microvessel density (MVD) was calculated on slides stained with CD34 antibody. Spearman's rank correlation was performed to evaluate the correlation between the frequencies of Tregs in TILs and VEGF values, as well as between frequencies of Tregs and MVD determinations.
RESULTSCompared to healthy controls, the frequency of peripheral blood Tregs was significantly increased in patients with RCC (P < 0.05). The percentage of tumor-infiltrating Tregs was higher than that of peripheral blood Tregs in patients with RCC (P < 0.01). In addition, the frequency of tumor-infiltrating Tregs was shown to significantly correlate with the pathological stage (P < 0.05) and nuclear grade (P < 0.01). Importantly, a significant positive correlation was observed between the frequency of tumor-infiltrating Tregs and VEGF protein expression (r = 0.51, P < 0.05), as well as between frequencies of Tregs and MVD score (r = 0.39, P < 0.05).
CONCLUSIONSThese observations suggest that the high pro-angiogenic status of RCC may be associated with the accumulation of Tregs in the local microenvironment. Angiogenesis networks may be connected with immune tolerance units and cooperate with each other to facilitate tumor growth and progression.
Adult ; Aged ; Carcinoma, Renal Cell ; immunology ; metabolism ; Cells, Cultured ; Enzyme-Linked Immunosorbent Assay ; Female ; Flow Cytometry ; Humans ; Immunohistochemistry ; Kidney Neoplasms ; immunology ; metabolism ; Lymphocytes, Tumor-Infiltrating ; immunology ; Male ; Middle Aged ; Neovascularization, Pathologic ; immunology ; metabolism ; T-Lymphocytes, Regulatory ; immunology
7.General characteristics and clinical practices of Chinese patients with non-alcoholic fatty liver disease.
Min-de ZENG ; Bing-yuan WANG ; Cheng-wei CHEN ; Rui-hua SHI ; You-ming LI ; Xiao-hua HOU ; Shi-ying XUAN ; Xiao-ping ZOU ; Yu-yuan LI ; Jia-ji JIANG ; Zhen-ya SONG ; Jian-gao FANG ; Yi-min MAO
Chinese Journal of Hepatology 2011;19(5):362-366
OBJECTIVETo assess the characteristics and daily treatment compliance of non-alcoholic fatty liver disease (NAFLD) patients in China.
METHODSNAFLD adult patients from 21 clinics of 12 cities in China were enrolled in this registry. Physical examination such as demographic characteristics (height, weight, waist circumference measurement), blood pressure and clinical laboratory and ultrasonographic examination of liver were undertaken. Daily practice including life style and medication were recorded and assessed in accordance with 2006 Chinese NAFLD treatment guidelines.
RESULTSA total of 1656 patients were enrolled (1146 male and 510 female), mean of 45.8 ± 12.6 years old, mean duration of NAFLD history was (47.2 ± 47.7) months. 44.9% of NAFLD were suffering from metabolic syndromes. Patients with central obesity have higher incidence of hypertension and lower level of high-density lipoprotein cholesterol (HDL-C) than those without central obesity, P < 0.05. Body mass index (BMI), waist circumference, triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) in ALT abnormal group were higher than those in ALT normal group (P < 0.05), HDL-C was lower in ALT abnormal group (P < 0.05). Significant differences existed between the BMI, female waist circumference, TG, fast insulin, HOMA index, ALT, AST and HDL-C among subgroups with mild, moderate and severe steatosis. Majority of the patients did not follow recommendations of NAFLD treatment guidelines. Among targeted population only 15.3% of patients used insulin sensitizers and 23.8% took lipid lowering medicine according to the guideline.
CONCLUSIONData indicated that nearly half of NAFLD patients co-morbid with metabolic disorders. Therapy compliance was unsatisfactory and the gap between current practice and Chinese NAFLD treatment guidelines was not optimal.
Adult ; Asian Continental Ancestry Group ; China ; epidemiology ; Fatty Liver ; diagnosis ; epidemiology ; therapy ; Female ; Humans ; Male ; Metabolic Syndrome ; epidemiology ; Middle Aged ; Non-alcoholic Fatty Liver Disease ; Risk Factors ; Waist Circumference
8.Methylation Status of Transcriptional Modulatory Genes Associated with Colorectal Cancer in Northeast China.
Han Lu GAO ; Xuan WANG ; Hong Ru SUN ; Jun De ZHOU ; Shang Qun LIN ; Yu Hang XING ; Lin ZHU ; Hai Bo ZHOU ; Ya Shuang ZHAO ; Qiang CHI ; Yu Peng LIU
Gut and Liver 2018;12(2):173-182
BACKGROUND/AIMS: Methylation status plays a causal role in carcinogenesis in targeted tissues. However, the relationship between the DNA methylation status of multiple genes in blood leukocytes and colorectal cancer (CRC) susceptibility as well as interactions between dietary factors and CRC risks are unclear. METHODS: We performed a case-control study with 466 CRC patients and 507 cancer-free controls to investigate the association among the methylation status of individual genes, multiple CpG site methylation (MCSM), multiple CpG site heterogeneous methylation and CRC susceptibility. Peripheral blood DNA methylation levels were detected by performing methylation-sensitive high-resolution melting. RESULTS: Total heterogeneous methylation of CA10 and WT1 conferred a significantly higher risk of CRC (adjusted odds ratio [OR(adjusted)], 5.445; 95% confidence interval [CI], 3.075 to 9.643; OR(adjusted), 1.831; 95% CI, 1.100 to 3.047; respectively). Subjects with high-level MCSM (MCSM-H) status demonstrated a higher risk of CRC (OR(adjusted), 4.318; 95% CI, 1.529 to 12.197). Additionally, interactions between the high-level intake of fruit and CRH, WT1, and MCSM on CRC were statistically significant. CONCLUSIONS: The gene methylation status of blood leukocytes may be associated with CRC risk. MCSM-H of blood leukocytes was associated with CRC, especially in younger people. Some dietary factors may affect hypermethylation status and influence susceptibility to CRC.
Carcinogenesis
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Case-Control Studies
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China*
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Colorectal Neoplasms*
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DNA Methylation
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Freezing
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Fruit
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Humans
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Leukocytes
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Methylation*
;
Odds Ratio
9.Mechanism of Yanghe Decoction against subcutaneous tumor in pulmonary metastasis from breast cancer through HIF-1α signaling pathway regulating glycolysis:based on network pharmacology and animal experiment.
Yang-Jing LIU ; Xiao-Liu LI ; Chao-Qun MA ; De-Xuan CHEN ; Gao-Yuan WANG ; Tai-Yang ZHU
China Journal of Chinese Materia Medica 2023;48(9):2352-2359
This study aims to explore the mechanism of Yanghe Decoction(YHD) against subcutaneous tumor in pulmonary metastasis from breast cancer, which is expected to lay a basis for the treatment of breast carcinoma with YHD. The chemical components of medicinals in YHD, and the targets of the components were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The disease-related targets were searched from GeneCards and Online Mendelian Inheritance in Man(OMIM). Excel was employed to screen the common targets and plot the Venn diagram. The protein-protein interaction network was constructed. R language was used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment. A total of 53 female SPF Bablc/6 mice were randomized into normal group(same volume of normal saline, ig), model group(same volume of normal saline, ig), and low-dose and high-dose YHD groups(YHD, ig, 30 days), with 8 mice in normal group and 15 mice in each of the other groups. Body weight and tumor size was measured every day. Curves for body weight variation and growth of tumor in situ were plotted. In the end, the subcutaneous tumor sample was collected and observed based on hematoxylin and eosin(HE) staining. The mRNA and protein levels of hypoxia inducible factor-1α(HIF-1α), pyruvate kinase M2(PKM2), lactate dehydrogenase A(LDHA), and glucose transporter type 1(GLUT1) were detected by PCR and Western blot. A total of 213 active components of YHD and 185 targets against the disease were screened out. The hypothesis that YHD may regulate glycolysis through HIF-1α signaling pathway to intervene in breast cancer was proposed. Animal experiment confirmed that the mRNA and protein levels of HIF-1α, PKM2, LDHA, and GLUT1 in the high-and low-dose YHD groups were lower than those in the model group. YHD has certain inhibitory effect on subcutaneous tumor in pulmonary metastasis from breast cancer in the early stage, which may intervene pulmonary metastasis from breast cancer by regulating glycolysis through HIF-1α signaling pathway.
Female
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Mice
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Animals
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Glucose Transporter Type 1/genetics*
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Network Pharmacology
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Animal Experimentation
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Saline Solution
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Drugs, Chinese Herbal/therapeutic use*
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Medicine, Chinese Traditional
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Signal Transduction
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Glycolysis
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RNA, Messenger
;
Neoplasms/drug therapy*
;
Molecular Docking Simulation
10.A multicenter epidemiological study of acute bacterial meningitis in children.
Cai Yun WANG ; Hong Mei XU ; Jiao TIAN ; Si Qi HONG ; Gang LIU ; Si Xuan WANG ; Feng GAO ; Jing LIU ; Fu Rong LIU ; Hui YU ; Xia WU ; Bi Quan CHEN ; Fang Fang SHEN ; Guo ZHENG ; Jie YU ; Min SHU ; Lu LIU ; Li Jun DU ; Pei LI ; Zhi Wei XU ; Meng Quan ZHU ; Li Su HUANG ; He Yu HUANG ; Hai Bo LI ; Yuan Yuan HUANG ; Dong WANG ; Fang WU ; Song Ting BAI ; Jing Jing TANG ; Qing Wen SHAN ; Lian Cheng LAN ; Chun Hui ZHU ; Yan XIONG ; Jian Mei TIAN ; Jia Hui WU ; Jian Hua HAO ; Hui Ya ZHAO ; Ai Wei LIN ; Shuang Shuang SONG ; Dao Jiong LIN ; Qiong Hua ZHOU ; Yu Ping GUO ; Jin Zhun WU ; Xiao Qing YANG ; Xin Hua ZHANG ; Ying GUO ; Qing CAO ; Li Juan LUO ; Zhong Bin TAO ; Wen Kai YANG ; Yong Kang ZHOU ; Yuan CHEN ; Li Jie FENG ; Guo Long ZHU ; Yan Hong ZHANG ; Ping XUE ; Xiao Qin LI ; Zheng Zhen TANG ; De Hui ZHANG ; Xue Wen SU ; Zheng Hai QU ; Ying ZHANG ; Shi Yong ZHAO ; Zheng Hong QI ; Lin PANG ; Cai Ying WANG ; Hui Ling DENG ; Xing Lou LIU ; Ying Hu CHEN ; Sainan SHU
Chinese Journal of Pediatrics 2022;60(10):1045-1053
Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ2=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent
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Brain Abscess
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Child
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Child, Preschool
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Escherichia coli
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Female
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Humans
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Hydrocephalus
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Infant
;
Infant, Newborn
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Male
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Meningitis, Bacterial/epidemiology*
;
Retrospective Studies
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Streptococcus agalactiae
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Streptococcus pneumoniae
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Subdural Effusion
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beta-Lactamases