In order to solve the problem of resistance of Pseudomonas aeruginosa to multiple antibiotics, it is an effective way to find inhibitors of P. aeruginosa efflux pump. In this study, 15 new ornithine peptidomimetic derivatives were designed and synthesized by changing the side chain structure of natural amino acids with PAβN, a dipeptide efflux pump inhibitor, and their synergic activity with aztreonam, a monocyclic β-lactam antibiotic, against P. aeruginosa was evaluated. Among them, the representative compound 12b not only enhanced the antibacterial activity of β-lactam antibiotics aztreonam, ceftazidime and meropenem, but also significantly enhanced the antibacterial action of macrolide antibiotics clarithromycin, showing a broad-spectrum synergic sensitization effect. In addition, compound 12b also has a good safety. Preliminary mechanisms suggest that 12b works by directly targeting the efflux transporter MexB. These results provide a new lead compound for the development of a new class of efflux pump inhibitors against P. aeruginosa.

OBJECTIVETo study the safety and effects of mini-margin nephron sparing surgery (NSS) for renal cell carcinoma (RCC).

METHODSFrom January 1998 to December 2006, 115 cases of RCC with diameter of 4 cm or less and stage of T1aN0M0 were treated with NSS using a margin of 5 mm or more. The mean diameter of the tumors was 3.3 cm (range 1.0-4.0 cm). Of the cases, 3 were with synchronous bilateral cancer while 112 cases were with normal opposite kidneys. The clinical results were followed and analyzed.

RESULTSAll of the operations were technically successful. The mean duration of surgical procedures was 90 min (ranged 80-120 min). The blood loss was 50 -200 ml. No patient needed blood transfusion. Renal arteries were occluded in 98 cases under hypothermic technique for a mean duration of 22 min (20-25 min). While in 17 cases, renal parenchyma squeezing was used for bleeding control. All of the 115 cases were of negative margin by weather frozen or routine pathologic study. The mean follow-up was 62 months (6-96 months). Local recurrence was found in 1 case during follow-up, with a local recurrence rate of 0.9%, while no distant metastasis was detected. All the patients were alive with no evidence of tumor bearing until last evaluation. Secondary gross hematuria occurred in 3 cases during hospital stay and cured by bed limitation. There were no major complications such as bleeding and urinary leakage or urinoma requiring re-operation.

CONCLUSIONSMini-margin nephron sparing surgery is likewise safe and effective in treating early localized renal cell carcinoma 4 cm or less. It provides excellent renal function preservation, favorable long-term progression-free survival, and is not associated with an increased risk of local recurrence.

Adult ; Aged ; Carcinoma, Renal Cell ; surgery ; Female ; Follow-Up Studies ; Humans ; Kidney Neoplasms ; surgery ; Male ; Middle Aged ; Nephrectomy ; methods ; Treatment Outcome

OBJECTIVETo investigate the expression of P53 protein and its clinical significance in prostatic carcinoma.

METHODSFormalin-fixed, paraffin-embedded tissue sections from 45 cases of prostatic carcinoma (PCa) and 10 cases of benign prostate hyperplasia (BPH) were analyzed retrospectively with immunohistochemical Elivision staining method. The relationship of P53 expression with prostate cancer stage, grade, PSA, endocrine therapeutic effect and prognosis was evaluated.

RESULTSThe positive staining rates of p53 protein expression were 51.1% and 10.0% respectively in patients with PCa and BPH (P < 0.05); 70.0% and 25.0% in PCa patients at pathological stage D and stages A approximately C respectively (P < 0.05); 14.3% and 56.7% in those with Gleason score < or = 7 and > 7 (P < 0.05); 20.0% and 60.0% in those with PSA < or = 10 microg/L and PSA > 10 micro/L (P > 0.05 ); 25.0% and 72.3% in those who responded to endocrine therapy and those who failed to respectively (P < 0.05). Log Rank analyses showed that the survival time of the PCa patients with negative P53 expression was obviously longer than those with the positive (P < 0.05 ).

CONCLUSIONThere were correlations between P53 expression and tumor grade, tumor stage and survival time, so the expression of P53 could be regarded as a prognostic molecular marker and a predictor of endocrine therapeutic effect for prostate cancer.

Aged ; Aged, 80 and over ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Prognosis ; Prostate-Specific Antigen ; metabolism ; Prostatic Hyperplasia ; metabolism ; pathology ; Prostatic Neoplasms ; metabolism ; pathology ; Staining and Labeling ; Tumor Suppressor Protein p53 ; biosynthesis

OBJECTIVETo investigate the effect of new bone formation in sinus augmentation with guided bone regeneration (GBR) using collagen membranes.

METHODSThe first maxillary molars of 18 adult female Beagle dogs were extracted and the sinus floors of both sides were lifted with simultaneous implantation. A combination of autografts and Bio-Oss in a 2:1 ratio was placed in the space under the membrane. On the experimental side in each dog, the collagen membrane was folded at the lateral osteotomy window, the apex of the implants and a certain part of palatal bone. On the contralateral control side, the collagen membrane only covered the osteotomy window. Six animals were sacrificed at 4, 12, and 24 weeks respectively after surgery. Gross observation, biomechanical testing and histological examinations were performed.

RESULTSThe translocation of grafted materials and bone absorption were found on the top of implants in the control side, and the grafted materials kept original shape at the experimental side at 4th week. The granule of Bio-oss absorbed obviously at 12th and 24th week. The pull-out force increased with time. At 24th week, the force of pull out was 558.1 ± 37.4 N at the study side, and 471.4 ± 31.5 N at the control side. There was a significant difference in the pull-out force was noted between the two groups (P < 0.01). Histological examination showed new bone formation on the sinus floor, and the grafted materials gradually reduced with time

CONCLUSIONSGBR with the enfolded-coverage of the membrane can effectively decrease absorption of the grafted materialon the apical surface of implants and stimulate new bone formation in the sinus augmentation.

Animals ; Collagen ; Dental Implantation ; Dental Implants ; Dogs ; Female ; Guided Tissue Regeneration ; Male ; Maxilla ; Maxillary Sinus ; surgery ; Minerals ; Molar ; Osteogenesis ; physiology ; Sinus Floor Augmentation ; methods ; Tooth Extraction

Objective To investigate the effect of nucleotide-binding oligomerization domaincontaining protein 1 (NOD1) on pyroptosis in hepatic ischemia-reperfusion injury.Methods An animal model of ischemia-reperfusion injury was established.Thirty healthy,male,and clean C57 BL mice were randomly divided into sham operation group (sham group) and ischemia-reperfusion group (IR,including 2 h,6 h,12 h,24 h subgroups),6 per group.Serum ALT and AST levels in each group were measured by blood biochemistry.HE staining and TUNEL were used to observe the pathological changes of liver and hepatocyte apoptosis.Immunohistochemistry was used to detect the expression and distribution of NOD1 in each group.Western blotting was used to detect NOD1,MM2,pro-Caspase-1 and active-Caspase-1 expression.NOD1 siRNA and empty control siRNA were transfected into AML12 cells,then the hypoxia/reoxygenation model was established and cells were collected to detect the expression of NOD1,AIM2 and active-Caspase-1.Results The ALT and AST levels in IR group were significantly higher than those in sham group,and peaked at IR 12-h subgroup (P＜0.05).HE staining showed that hepatic injury was the most severe at 12 h after reperfusion.TUNEL results showed that the number of apoptotic cells was the greated at 12 h after reperfusion.Western blotting showed that NOD1 protein expression was highest at 12 h after reperfusion.With the prolongation of reperfusion time,the expression of AIM2 and active-Caspase-1 gradually increased,and that of pro-Caspase-1 gradually decreased.The expression of NOD1,AIM2 and activeCaspase-1 decreased after transfection of NOD1 siRNA into AML12 cells.Conclusions NOD1 promotes liver ischemia-reperfusion injury,which may be related to NOD1 promoting liver injury by activating pyroptosis.

OBJECTIVETo evaluate the effect and safety of transurethral prostatectomy with the bipolar plasmakinetic technique (PKRP) in the treatment of benign prostate hyperplasia (BPH).

METHODSA total of 712 BPH patients underwent transurethral prostatectomy with the bipolar plasmakinetic technique. The patients averaged 70.6 years of age and 52 g (range 35-102 g) in estimated prostate weight preoperatively. Comparative analyses were made on the maximum urine flow rate (Qmax), residual urine volume and scores on IPSS and QOL obtained pre- and post-operatively.

RESULTSThe operations lasted 20-120 minutes (mean 51 min), the resected tissues weighed 15-96 g (mean 46 g), and no transurethral resection syndrome (TURS) occurred. The catheters were removed 4 -5 days after surgery. The patients were followed up for 1 -52 months (mean 27.6 mo). Obvious reduction was observed in the average Qmax from 4.7 ml/s preoperatively to 19. 1 ml/s postoperatively, in the mean IPSS score from 26.6 to 5. 8, and in the mean QOL score from 5.4 to 1.7, all with significant differences (P < 0.01).

CONCLUSIONTransurethral prostatectomy with the bipolar plasmakinetic technique is a safe and effective means for the treatment of BPH.

Aged ; Aged, 80 and over ; Humans ; Male ; Middle Aged ; Prostatic Hyperplasia ; surgery ; Transurethral Resection of Prostate ; methods ; Treatment Outcome

OBJECTIVETo observe the effect of the combined therapy of intervention, operation and biology in patients with middle-advanced renal cell carcinoma.

METHODSCombined therapy was used in 52 cases as combined care groups and the single operational therapy was used in 50 cases as control group. Compare their resection rates, surgical risks and 3, 5 years survival rates.

RESULTSIn the combined care group, the excision rate was 100%, the average amount of blood transfusion during the operation was 280 ml, the average operation time was 100 minutes, and the 3, 5 years survival rates were 73% and 50%; While in the control group, the results were 90%, 396 ml, 130 minutes, 55% and 27% respectively. There were significant differences between 2 groups (P < 0.05).

CONCLUSIONCombined therapy could elevate resection rates and 3, 5 years survival rates and decrease surgical risks.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cancer Vaccines ; therapeutic use ; Carcinoma, Renal Cell ; pathology ; therapy ; Combined Modality Therapy ; Embolization, Therapeutic ; Female ; Follow-Up Studies ; Humans ; Kidney Neoplasms ; pathology ; therapy ; Male ; Middle Aged ; Neoplasm Staging ; Survival Rate

OBJECTIVETo evaluate the effect and safety of transurethral prostatectomy with the bipolar plasma kinetic technique (PKRP) in the treatment of benign prostate hyperplasia(BPH).

METHODSTwo hundred and ninty-seven BPH patients underwent transurethral prostatectomy with the bipolar plasma kinetic technique. The preoperative estimated weight of the prostate ranged from 35 g to 102 g, averaging 52 g.

RESULTSThe operation lasted 40 approximately 65 min, averaging 51 min. The resected tissues weighed 40 approximately 80 g, averaging 46 g. During the operation no transurethral resection (TUR) syndrome occurred. The catheter was removed 4 approximately 5 days after the operation, all with fluent urination. The patients were followed up for 2 approximately 33 months. IPSS decreased from average 31.5 preoperatively to average 6.8 postoperatively (P < 0.001). Average maximum flow-rate (Q(max)) decreased from 6.3 ml/s preoperatively to 18.6 ml/ s postoperatively (P < 0.001). Preoperative average residual urine was 97 ml and reduced to average 9 ml after the operation. Temporary incontinence occurred in 4 cases, perioperative hemorrhage in 2, and urethral stricture in 1.

CONCLUSIONTransurethral prostatectomy with the bipolar plasma kinetic technique is a safe and effective means for the treatment of BPH.

Aged ; Aged, 80 and over ; Humans ; Male ; Middle Aged ; Prostatic Hyperplasia ; surgery ; Transurethral Resection of Prostate ; methods ; Treatment Outcome

BACKGROUNDCurrent surgical practice for nephron sparing surgery allows at least 1 cm margin of normal tissue around the tumour. However, recent studies show that the width of the margin is not important, even simple enucleation is as effective as partial nephrectomy. We explored whether margin size has significant impacts on clinical outcomes in nephron sparing surgery for renal cell carcinoma of 4 cm or less.

METHODSBetween 1998 and 2006, 115 patients with sporadic, pathologically confirmed, renal cell carcinoma 4 cm or less (T1a) and normal contralateral kidney were treated by nephron sparing surgery using a margin less than 5 mm. The surgical margin status was evaluated from frozen and permanent paraffin sections.

RESULTSMean and median tumour diameter were 3.3 cm and 3.5 cm (range 1.0-4.0). The mean margin width was 2.2 mm (median 2.0, range 0-6). In addition, 114 cases had margins 5 mm or less (99.1%), 97 cases (84.3%) had margin 3 mm or less, and 26 cases had margin zero (22.6%). None of the patients had positive surgical margins. No patients died during follow-up (mean 65 months). There were no any major surgical complications and no distant metastasis was detected. Local recurrence was detected in one case (0.9%) at a different site of the kidney.

CONCLUSIONSFor early localized renal cell carcinoma of 4 cm or less, as long as tumour is completely excised, the size of margin in nephron sparing surgery is not important. Nephron sparing surgery with 5 mm margin is enough for tumour control. It provides excellent renal function preservation, favourable long term progression free survival and is not associated with an increased risk of local recurrence.

Adult ; Aged ; Carcinoma, Renal Cell ; pathology ; surgery ; Female ; Humans ; Kidney Neoplasms ; pathology ; surgery ; Male ; Middle Aged ; Nephrons ; surgery

Objective To explore the molecular epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae(CRKP),and reveal its mechanism of resistance to ceftazidime/avibactam(CZA).Methods CZA-re-sistant CRKP strains initially isolated from the Affiliated Hospital of Xuzhou Medical University from January 2021 to September 2023 were collected.The carriage of 5 carbapenemase genes(blaKPC,blaNDM,blaOXA,blaVIM,blaIMp)were detected with gene amplification method and colloidal gold method.The relative copy number and expression level of Klebsiella pneumoniae(KP)carbapenemase-producing KP(KPC-KP)was detected with real-time quantita-tive polymerase chain reaction(RT-qPCR),mutation sites of KPC mutation strains were analyzed with whole-ge-nome sequencing,and epidemic characteristics of CRKP and resistance mechanism to CZA were analyzed.Results A total of 73 CZA-resistant CRKP strains were isolated,with 37(50.68％)being KPC and NDM co-producing strains,33(45.21％)NDM-producing alone(23 strains producing NDM-5 and 10 strains producing NDM-1),and 3 KPC-producing alone.KP-2842 strain was identified as ST11-type KPC-33 variant,KP-2127 and KP-2189 strains produced KPC-2.Compared with KP ATCC BAA-1705,the copy number of blaKPC in these strains up-regulated by 1.04-3.86 fold,and the expression increased by 6.66-12.93 fold,respectively.Colloidal gold and PCR methods demonstrated good consistency and the ability to detect the enzyme co-producing and KPC-33 variant.Conclusion In this hospital,the resistance of CRKP to CZA is primarily mediated by the metalloenzyme NDM,with co-produc-tion of NDM and KPC being a characteristic of CRKP.High copy number and expression level of blaKPC-2 also con-tribute to CZA resistance.This study identified the KPC-33 variant for the first time in ST11-type CRKP in Jiangsu Province.