Determining the Disinfectants Resistance Genes and the Susceptibility to Common Disinfectants of Extensively Drug-Resistant Carbapenem-Resistant Klebsiella pneumoniae Strains at a Tertiary Hospital in China.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection has become a significant threat to global health. The application of chemical disinfectants is an effective infection control strategy to prevent the spread of CRKP in hospital environments. However, bacteria have shown reduced sensitivity to clinical disinfectants in recent years. Furthermore, bacteria can acquire antibiotic resistance due to the induction of disinfectants, posing a considerable challenge to hospital infection prevention and control. This study collected 68 CRKP strains from the Fifth Affiliated Hospital of Xinjiang Medical University in China from 2023 to 2024. These strains were isolated from the sputum, urine, and whole blood samples of patients diagnosed with CRKP infection. Antibiotic susceptibility tests were performed on CRKP strains. Concurrently, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of disinfectants (benzalkonium bromide, 1% iodophor disinfectant, alcohol, and chlorine-containing disinfectant) against the test isolates were determined by the broth microdilution method. The efflux pump genes (cepA, qacE, qacEΔ1, qacEΔ1-SUL1, oqxA, and oqxB) were detected using polymerase chain reaction. The results showed that 21 out of the 68 CRKP strains exhibited extensive drug resistance, whereas 47 were nonextensively drug-resistant. The MIC value for benzalkonium bromide disinfectants displayed statistically significant differences (p < 0.05) between extensively drug-resistant (XDR) and non-XDR strains. Additionally, the MBC values for benzalkonium bromide disinfectants and 1% iodophor disinfectants displayed statistically significant differences (p < 0.05) between XDR and non-XDR strains. The detection rates for the efflux pump genes were as follows: cepA 52.9%, qacE 39.7%, qacEΔ1 35.2%, qacEΔ1-SUL1 52.9%, oqxA 30.8%, and oqxB 32.3%. The detection rate of the qacEΔ1-SUL1 gene in XDR CRKP strains was significantly higher than in non-XDR CRKP strains (p < 0.05). This indicates a potential link between CRKP bacterial disinfectant efflux pump genes and CRKP bacterial resistance patterns. Ongoing monitoring of the declining sensitivity of XDR strains against disinfectants is essential for the effective control and prevention of superbug.

Efficacy of Random Forest Models in Predicting Multidrug-Resistant Gram-Negative Bacterial Nosocomial Infections Compared to Traditional Logistic Regression Models.

This study evaluates whether random forest (RF) models are as effective as traditional Logistic Regression (LR) models in predicting multidrug-resistant Gram-negative bacterial nosocomial infections. Data were collected from 541 patients with hospital-acquired Gram-negative bacterial infections at two tertiary-level hospitals in Urumqi, Xinjiang, China, from August 2022 to November 2023. Relevant literature informed the selection of significant predictors based on patients' pre-infection clinical information and medication history. The data were split into a training set of 379 cases and a validation set of 162 cases, adhering to a 7:3 ratio. Both RF and LR models were developed using the training set and subsequently evaluated on the validation set. The LR model achieved an accuracy of 84.57%, sensitivity of 82.89%, specificity of 80.10%, positive predictive value of 84%, negative predictive value of 85.06%, and a Yoden index of 0.69. In contrast, the RF model demonstrated superior performance with an accuracy of 89.51%, sensitivity of 90.79%, specificity of 88.37%, positive predictive value of 87.34%, negative predictive value of 91.57%, and a Yoden index of 0.79. Receiver operating characteristic curve analysis revealed an area under the curve of 0.91 for the LR model and 0.94 for the RF model. These findings indicate that the RF model surpasses the LR model in specificity, sensitivity, and accuracy in predicting hospital-acquired multidrug-resistant Gram-negative infections, showcasing its greater potential for clinical application.

Imaging and therapy of hSSTR2-transfected tumors using radiolabeled somatostatin analogs.

The aim of this study was to introduce human somatostatin receptors subtype-2 (hsstr2) gene into A549 lung carcinoma cells in order to investigate the role of these receptors, and to observe the lethal effect of (131)I-RC-160 (RC-160, vapreotide, an analog of somatostatin) on transfected cells through tumor scintigraphy. Clones overexpressing SSTR2 were selected for radioligand-receptor binding assay and assessment of (125)I-RC-160 internalization. The methylthiazolyl tetrazolium test was used to observe the lethal effect of (131)I-RC-160, Na(131)I, and RC-160 on hSSTR2-transfected A549 cells (A549-hSSTR2). Planar imaging was performed with a gamma camera equipped with pinhole collimator in nude mice bearing both A549-hSSTR2 tumors overexpressing SSTR2 and A549-pcDNA3 (pcDNA3-transfected A549 cells) tumors as control. Images were obtained at 0.5, 6, and 24 h after injection of 3.7 × 10(6) Bq (99m)Tc-RC-160 via the tail vein. The inhibitory effects of (131)I-RC-160, RC-160, and Na(131)I on the tumors were recorded by measuring the tumor volumes. At the end of the study, the tumors were excised and HE staining was performed. The binding radioactivity (sum of membrane-bound and internalized radioligand) of A549-hSSTR2 cells was 18.24 ± 1.9 % of total counts added after 1 h of incubation, and was higher than that of A549-pcDNA3 cells 5.7 ± 1.4 % (P < 0.05). The inhibition ratio of A549-hSSTR2 cells was 78.8 ± 5.9 %. Clear images of tumor lesions in nude mice were achieved at 0.5 h post injection. In the A549-hSSTR2 xenograft tumor group, the growth of the tumors treated with (131)I-RC-160 was significantly inhibited as compared to tumors in the group treated with RC-160 (P < 0.01). This study demonstrated that it was possible to introduce hsstr2 to non-expressing tumor cell lines and treat tumors with radiolabeled somatostatin analogs.

Correlation between 99mTc-HYNIC-octreotide SPECT/CT somatostatin receptor scintigraphy and pathological grading of meningioma.

The aim of this study was to explore the association of (99m)Tc-HYNIC-octreotide SPECT/CT somatostatin receptor scintigraphy (SRS) with the pathological grading and expression of somatostatin receptor 2 (SSTR2) for meningioma, and to define possible roles of SRS in the pathological grading of meningioma. Thirty patients with meningiomas diagnosed by MRI and treated with (99m)Tc-HYNIC-octreotide SPECT/CT SRS. Meningioma tissues were obtained from analyzing pathological grading and measuring the expression of SSTR2 with immunohistochemical staining. The meningioma side (T) to the contralateral side (NT) ratios (T/TN) of radioactive counts were calculated to investigate their association with the pathological grading of meningioma and the expression of SSTR2. All 30 cases showed high meningioma radioactivity accumulation using SRS with a sensitivity of 100 %, while CT scans only detected 25 cases with a sensitivity of 83 %. Twenty cases with grade I meningioma had a T/NT ratio of 3.80 ± 1.67, which was significantly lower than the other 10 cases (9.57 ± 3.78) with a grade II meningioma (P < 0.01). All meningiomas expressed SSTR2 as detected by immunohistochemical staining, and the T/NT ratio was positively associated with the pathological grading of meningioma and the expression of SSTR2 (with r of 0.784 and 0.805, respectively). (99m)Tc-HYNIC-octreotide SPECT/CT SRS is a sensitive technique for detecting meningioma, and the T/NT ratio of the SRS data closely correlates with the pathological grade of meningioma and the expression of SSTR2.

Treatment of cystic craniopharyngioma with phosphorus-32 intracavitary irradiation.

PURPOSE: The aim of the study was to evaluate the effect of phosphorus-32 colloid ([(32)P]) intracavitary irradiation on the treatment of patients with cystic craniopharyngiomas. METHODS: Twenty patients with predominantly cystic craniopharyngiomas were admitted from 1981 to 2006. Eleven patients had [(32)P] intracavitary irradiation by stereotactic injection or Ommaya cyst instillation as the primary treatment, and the remaining nine had the same internal irradiation as an adjuvant treatment after tumor resection. A calculated irradiation dose of 400 approximately 500 Gy per once was delivered to the cyst wall. CONCLUSION: The patients were followed up ranging from 36 to 336 months; no operative morbidity or mortality was found from [(32)P] intracavitary irradiation. Fourteen patients (70%) had tumor progression and required further two to four times intracavitary irradiation. All 20 cases achieved tumor shrinkage or stabilization with effective outcome 3-6 months after the last [(32)P] therapy. For patients with cystic craniopharyngioma, [(32)P] administration by stereotactic injection or Ommaya cyst instillation is a safe and helpful option, which could improve the life quality, prolong the life span, and enhance the survival rate of cystic craniopharyngioma patients.

Effects of basic fibroblast growth factor microspheres on angiogenesis in ischemic myocardium and cardiac function: analysis with dobutamine cardiovascular magnetic resonance tagging.

OBJECTIVE: Therapeutic angiogenesis with angiogenic growth factors has described as one of the promising methods for collateral formation in the treatment of ischemic heart diseases. The purpose of this study is to assess the value of intramyocardial injection of slow-released basic fibroblast growth factor microspheres on angiogenesis and cardiac function in the early period of acute infarcted myocardium with dobutamine cardiovascular magnetic resonance tagging. METHODS: Acute myocardial infarction was made by ligation of the left anterior descending coronary artery distal to its first diagonal branch. Immediately after coronary artery occlusion, 1 ml of saline containing 100 microg of basic fibroblast growth factor microspheres was injected into peri-infarct myocardial area in the basic fibroblast growth factor group, whereas only gelatin hydrogel microspheres with 1 ml of saline was given in control dogs. Cardiac function was evaluated by cine magnetic resonance imaging. Dobutamine cardiovascular magnetic resonance was performed at rest and during low doses of dobutamine to assess regional wall motion. Immunohistochemical study with von Willebrand factor was performed to observe angiogenesis. RESULTS: Left ventricular ejection fraction improved markedly 10 and 17 days after treatment in the basic fibroblast growth factor group. The basic fibroblast growth factor group had more viable myocardium. Microvessel density was higher in the basic fibroblast growth factor group than in the control group except the first day after treatment. CONCLUSIONS: Intramyocardial administration of basic fibroblast growth factor microspheres can promote the growth of microvessels and improve left ventricular function and myocardial viability in the early period of acute myocardial infarction.

Reduction in the recurrence of meningiomas by combining somatostatin receptor scintigraphy of (99m)Tc-HYNIC-octreotide SPECT/CT and radio guidance with a hand-held γ-probe during surgery.

PURPOSE: The aim of this study was to determine whether recurrence of meningiomas could be reduced by combining somatostatin receptor scintigraphy (SRS) of Tc-HYNIC-octreotide SPECT/CT and radio guidance with a hand-held γ-probe during surgery. MATERIALS AND METHODS: Thirty patients with meningiomas diagnosed by MRI and considered as the study group were treated with Tc-HYNIC-octreotide SPECT/CT preoperatively and pathologically examined postoperatively. Another 60 patients considered as the control group underwent only an MRI preoperatively and a pathological examination postoperatively. For the patients in the study group, meningiomas were removed by a hand-held γ-probe 4-12 h after SRS; these patients were followed up by MRI examination each year for 5 years to monitor the recurrence rate of the meningiomas. For the control group, routine operations without radio guidance were performed and followed up with MRI examination simultaneously. RESULTS: All patients in the study group, comprising 20 with grade I and 10 with grade II meningiomas, showed high Tc-HYNIC-octreotide accumulation with a sensitivity of 100% for SRS; four patients (13.3%) relapsed after a 5-year follow-up, including one (5%) patient with a grade I and three (30%) patients with a grade II meningioma. However, among the 60 control patients, 30 were of grade I and 30 were of grade II; 18 patients (30%) experienced recurrence, including five (16.7%) grade I patients and 13 (43.3%) grade II patients. There were significant differences in recurrence between the study group and the control group when considering all the patients and those in grade I and grade II (all P values were below 0.001). CONCLUSION: Tc-HYNIC-octreotide SPECT/CT SRS is a sensitive technique for detecting meningiomas, and radio guidance using a hand-held γ-probe with Tc-HYNIC-octreotide during surgery can significantly reduce the recurrence of meningiomas.

Efficacy of (99m)Tc-EDDA/HYNIC-TOC SPECT/CT scintigraphy in Graves' ophthalmopathy.

The aim of this study was to investigate the predictive role of the orbital somatostatin receptor scintigraphy with (99m)Tc-EDDA/HYNIC-TOC ((99m)Tc-TOC) to detect clinical stage of Graves' ophthalmopathy and the response to corticosteroid therapy. The subjects of the experiment were 46 patients with Graves' ophthalmopathy (GO) and four volunteers without eye disease or GO as the normal group (NG). Single photon emission computed tomography (SPECT), computed tomography (CT) and the left and right lateral position planar imaging of the heads of the all subjects were obtained 4 h after the intravenous injection of 555 MBq of (99m)Tc-TOC. The (99m)Tc-TOC SPECT/CT was repeated 3 months later. 35 (35/46) patients were received corticosteroid therapy (prednisolone, 10 mg po tid ) for 3 months, however, the other 11 patients as control groups did not receive any treatment. The treatment effect was evaluated both by the orbital (99m)Tc-TOC uptake and NOSPECS. A significant decrease in the O/OC ratio was observed in 22 GO patients between pre- and post-treatment (1.64 ± 0.13 vs. 1.21 ± 0.09, P < 0.05). There were neither significant difference of the O/OC ratio in 13 GO patients between pre- and post-treatment periods, nor significant difference in the 9 (9/11) patients before and after three months. Orbital (99m)Tc-TOC scintigraphy is a feasible technique to estimate the Graves' ophthalmopathy activity and predict the response to subsequent corticosteroid therapy in GO patients. The technique could be a useful tool for physicians not familiar with CAS determination.

Continuous low-dose-rate radiation of radionuclide phosphorus-32 for hemangiomas.

The study goal was to clarify the therapeutic effect and the absorbed dose of radionuclide phosphorus-32 for skin hemangiomas and the consequent risk of side effects in these patients. Phosphorus-32 is an ß emitter and is used for skin hemangioma treatment. In comparison with the few Gy per minute of the linear accelerators, the dose rate of phosphorus-32 for hemangiomas is much <1 Gy/hour; so, the latter is called low-dose-rate radiation. To achieve the therapeutic dose, continuous hours or days of radiation is necessary. For strawberry hemangiomas, the phosphorus-32 applicator was tightly placed on the lesion site for several hours until reaching therapeutic dose. The absorbed dose was estimated by radiochromic films. The absorbed dose of phosphorus-32 irradiation declined exponentially with a depth from 0 to 2.5 mm. Of the 316 patients with strawberry hemangiomas, the lesion disappeared completely within 3 months after one-time treatment in 259 cases (82%). For cavernous hemangiomas, 370KBq phosphorus-32 colloid was injected into the hemangioma each square centimeter, and the absorbed radiation was estimated by theoretical calculation. Forty-two of the 58 patients with cavernous hemangiomas (72%) had lesions that completely disappeared within 3 months after receiving one to six treatments. Thus, the phosphorus-32 for strawberry hemangiomas and the chromium phosphate-32 colloid for cavernous hemangiomas were clearly efficacious.

Safety and feasibility of percutaneous vertebroplasty with radioactive (153)Sm PMMA in an animal model.

PURPOSE: We investigated the safety and feasibility of the combination of samarium-153-ethylenediamine tetramethylene phosphonate ((153)Sm-EDTMP)-incorporated bone cement (BC) with percutaneous vertebroplasty (PVP) in dogs. METHODS AND MATERIALS: (153)Sm-EDTMP-incorporated BC was prepared by combining solid (153)Sm-EDTMP and polymethylmethacrylate (PMMA) immediately before PVP. It was then injected into the vertebrae of four healthy mongrel dogs (two males and two females) by PVP under CT guidance. Each dog was subjected to five PVP sessions at a (153)Sm-EDTMP dose of 30-70 mCi. The suppressive effect of local injection of (153)Sm-EDTMP on the hematopoietic system was evaluated through counting of peripheral blood cells. Distribution of (153)Sm-EDTMP-incorporated BC and the status of tissues adjacent to injected vertebrae were evaluated with SPECT, CT and MRI. Histopathology was carried out to assess the influence of PVP on the vertebra and adjacent tissues at the microscopic level. RESULTS: PVP was done successfully, and all dogs exhibited normal behavior and stable physical signs after procedures. (153)Sm-EDTMP-incorporated BC was concentrated mainly in target vertebrae, and the peripheral blood cells remained within normal range. The spinal cord and tissues around BC did not exhibit signs of injury even when the dosage of (153)Sm-EDTMP increased from 30 mCi to 70 mCi. CONCLUSION: A dose lower than 70 mCi of (153)Sm is safe when it was injected into vertebrae. (153)Sm-EDTMP-incorporated BC did not influence the effect of PVP. This means might strengthen anti-tumor activity locally for vertebra with osseous metastasis without damaging adjacent tissues.

Changes in vasoreactivity of rat large- and medium-sized arteries induced by hyperthyroidism.

Although the excess of thyroid hormones has been found to be associated with many effects on the heart and vasculature, the adaptive changes of various conductive and resistance arteries from different vasculature are largely unknown. In this study, we compared changes in vascular reactivity between aortic and femoral arterial rings in hyperthyroidism rat model. Our results indicate that daily gastric feeding of euthyrox to rat with dosage of 100 microg group (H1) or 200 microg group (H2) for 25 days was sufficient to induce a thyrotoxicosis. The serum TT3 and TT4 levels, heart weight (HW), body weight (BW), HW/BW ratio and mean diameter of myocardiac cells of the rat were significantly greater (P<0.05) in that two hyperthyroidism groups than in control group (E). It demonstrates that the gastric feeding of euthyrox may provide a reliable, cheaper and convenient method to induce hyperthyroid state with varying severity and duration. Our results also suggest that the contractile responses to phenylephrine (PE) and the relaxation responses to acetylcholine (Ach) or sodium nitroprusside (SNP) were reduced and enhanced, respectively, in vascular rings from H1 and H2 rats compared with E rats (P<0.05). The above vasoconstriction and vasorelaxation responses to agonists at least in large, elastic and medium-sized muscular arteries, which might be important vascular changes accounting for the enhancement of ventriculoatrial coupling and the reduction in peripheral vascular resistance during hyperthyroidism.

Combination therapy in A549 cells.

BACKGROUND AND AIM: We investigated the anti-tumor effect induced by the combination of the radiotherapeutic agent (131)I-RC-160 and the prodrug 5-FC in human non-small cell lung cancer (NSCLC) A549 cells that were co-expressing the human somatostatin receptor 2 gene (hSSTR2) and E. coli cytosine deaminase gene (CD). METHODS: We cloned both hSSTR2 and CD into a bicistronic mammalian expression plasmid and stably transfected it into A549 cells (pCIS-A549 cells). After antibiotic selection, SSTR expression in stable clones was determined by reverse transcription and polymerase chain reaction (RT-PCR), Western blot, flow cytometry and immunofluorescence analyses. To assess the in vivo targeting efficiency of the "engineered" A549 cells, the cells were subcutaneously injected into nude mice and the biodistribution of (99m)Tc-RC-160 was assessed at different time points. The tumor inhibitory effects of (131)I-RC-160 and/or 5-FC were evaluated by measurement of tumor growth and immunohistochemical analysis. RESULTS: Multiple analyses demonstrated the successful expression of hSSTR2 in A549 cells. In vivo radioimaging revealed specific targeting of RC-160 to the tumors derived from pCIS-A549 cells when compared to those from control A549 cells. The tumor inhibitory rate of pCIS-A549 tumors in the (131)I-RC-160 plus 5-FC-treated group was significantly higher than that in the single agent-treated group, control group and control tumors. CONCLUSION: Co-expression of the hSSTR2 and CD genes in tumor cells can selectively sensitize these cells to the infra-additive effects of radioisotope-labeled RC-160 and 5-FC in vivo. This approach offers a potential therapeutic strategy for the treatment of lung cancer.

Application of bFGF and BDNF to improve angiogenesis and cardiac function.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a survival factor for endothelial cells and expresses in the ischemic myocytes. The purpose of this study was to assess whether the simultaneous application of basic fibroblast growth factor (bFGF) and BDNF incorporating gelatin hydrogels improves angiogenesis and cardiac function in ischemic myocardium compared with bFGF applied alone. MATERIALS AND METHODS: Direct intramyocardial injection of 100 microg of bFGF plus 25 microg of BDNF, 100 microg of bFGF, or saline were performed in canine infarct model. Colored microspheres were injected to assess the regional myocardial blood flow. Cardiac function was evaluated by cine magnetic resonance imaging (MRI). Immunohistochemical staining and enzyme linked immunosorbent assay (ELISA) were used to observe the localization and expression of bFGF and BDNF protein, and myocardial microvessel density was assessed by von Willebrand factor staining. RESULTS: Left ventricular ejection fraction (LVEF) was higher in bFGF plus BDNF group than in saline or bFGF group. Blood flow of the peri-infarct region was increased by bFGF plus BDNF treatment. The distribution of bFGF and BDNF-positive cardiomyocytes was similar in three groups. The expression of bFGF and BDNF protein and microvessel density in bFGF plus BDNF group was higher than in the other two groups. CONCLUSIONS: This study indicates that the sustained dual release of bFGF and BDNF incorporating gelatin hydrogels can improve angiogenesis and left ventricular function in the ischemic myocardium compared with bFGF applied alone. bFGF plus BDNF administration may be a promising therapeutic strategy for the treatment of ischemic myocardium.

Construction and activity assay of the activating transcription factor 3 reporter vector pATF/CRE-luc.

Activating transcription factor 3 (ATF3), a member of the activating transcription factor/cAMP responsive element binding protein (ATF/CREB) family of transcription factors, is induced by many physiological stresses. To investigate the activity of ATF/CREB in cells with physiological stresses, we developed a practical reporter vector, the plasmid pATF/CRE-luc, bearing activating transcription factor/cAMP responsive element (ATF/CRE) binding sites. This plasmid was constructed by inserting three repeats of the ATF/CRE binding element into the plasmid pG5luc, replacing the GAL-4 binding sites. The plasmids pACT/ATF3 and pATF/CRE-luc were transfected into HeLa and NIH3T3 cells, respectively, and the results showed that the expression of luciferase was increased in a dose-dependent manner on plasmid pACT/ATF3. The data suggested that the plasmid pATF/CRE-luc could be used as a sensitive and convenient reporter system of ATF3 activity.

Direct technetium-99m labeling of anti-hepatoma monoclonal antibody fragment:a radioimmunoconjugate for hepatocellular carcinoma imaging.

AIM:To directly radiolabel an anti-hepatoma mAb fragment HAb18 F(ab')(2) with (99m)Tc by stannousreduced method, and assess the stability, biodistribution and radioimmun oimaging (R II).METHODS:Immunoreactive fraction was determined according to Lindmo's method. Ellman's reagent was used to determine the number of thiols in the reduced F(ab') (2). Labeling efficiency and homogeneity were measured by paper chromatography, sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE) and autoradiography. Challenge assay involved the incubation of aliquots of labeled antibody in ethylenediaminetetraacetate (EDTA) and L-cysteine (L-cys) solutions with different molar ratio at 37° for 1h, respectively. Investigations in vivo utilized nude mice bearing human hepatocellular carcinoma (HHCC) xenografts with gamma camera imaging and tissue biodistribution studies at regular intervals.RESULTS:The labeling procedure was finished within 1.5h compared with the pretinning method which would take at least 21h. In vitro studies demonstrated that the radiolabeled mAb fragment was homogeneous and retained its immunoreactivity. Challenge studies indicated that (99m)Tc-labeled HAb18 F(ab') (2) in EDTA is more stable than in L-cys. Imaging and biodistribution showed a significant tumor uptake at 24h post injection of (99m)Tc-labeled HAb18 F(ab') (2). The blood, kidney, liver and tumor uptakes at 24h were 0.56 ± 0.09, 56.45 ± 11.36,1.43 ± 0.27 and 6.57 ± 3.01 (%ID/g) respectively.CONCLUSION:(99m)Tc-HAb18 F(ab') (2) conjugate prepared by this direct method appears to be an effective way to detect hepatoma in nude mice model.