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PURPOSE: Enterobacteriaceae carrying mcr-9, in particularly those also co-containing metallo-ß-lactamase (MBL) and TEM type ß-lactamase, present potential transmission risks and lack adequate clinical response methods, thereby posing a major threat to global public health. The aim of this study was to assess the antimicrobial efficacy of a combined ceftazidime/avibactam (CZA) and aztreonam (ATM) regimen against carbapenem-resistant Enterobacter cloacae complex (CRECC) co-producing mcr-9, MBL and TEM. METHODS: The in vitro antibacterial activity of CZA plus ATM was evaluated using a time-kill curve assay. Furthermore, the in vivo interaction between CZA plus ATM was confirmed using a Galleria mellonella (G. mellonella) infection model. RESULTS: All eight clinical strains of CRECC, co-carrying mcr-9, MBL and TEM, exhibited high resistance to CZA and ATM. In vitro time-kill curve analysis demonstrated that the combination therapy of CZA + ATM exerted significant bactericidal activity against mcr-9, MBL and TEM-co-producing Enterobacter cloacae complex (ECC) isolates with a 100% synergy rate observed in our study. Furthermore, in vivo survival assay using Galleria mellonella larvae infected with CRECC strains co-harboring mcr-9, MBL and TEM revealed that the CZA + ATM combination significantly improved the survival rate compared to the drug-treatment alone and untreated control groups. CONCLUSION: To our knowledge, this study represents the first report on the in vitro and in vivo antibacterial activity of CZA plus ATM against CRECC isolates co-harboring mcr-9, MBL and TEM. Our findings suggest that the combination regimen of CZA + ATM provides a valuable reference for clinicians to address the increasingly complex antibiotic resistance situation observed in clinical microorganisms.
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Antibacterianos , Compuestos de Azabiciclo , Aztreonam , Ceftazidima , Combinación de Medicamentos , Enterobacter cloacae , Infecciones por Enterobacteriaceae , Pruebas de Sensibilidad Microbiana , beta-Lactamasas , Aztreonam/farmacología , Aztreonam/uso terapéutico , Compuestos de Azabiciclo/farmacología , Compuestos de Azabiciclo/uso terapéutico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Infecciones por Enterobacteriaceae/microbiología , Animales , Enterobacter cloacae/efectos de los fármacos , Enterobacter cloacae/genética , Ceftazidima/farmacología , Ceftazidima/uso terapéutico , Humanos , beta-Lactamasas/metabolismo , beta-Lactamasas/genética , Enterobacteriaceae Resistentes a los Carbapenémicos/efectos de los fármacos , Enterobacteriaceae Resistentes a los Carbapenémicos/genética , Quimioterapia Combinada , Mariposas Nocturnas/microbiología , Farmacorresistencia Bacteriana Múltiple/genética , Modelos Animales de EnfermedadRESUMEN
Developing low-cost, high-efficiency and stable electrocatalysts for the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER) is crucial but highly challenging. Density functional theory (DFT) calculations reveal that doping ruthenium (Ru) into catalysts can effectively optimize their electronic structure, hence leading to an optimal Gibbs free energy on the catalyst surface. Herein, an ultra-low Ru (about 2.34 wt%)-doped Ni3Se2 nanowire catalyst (i.e., Ru/Ni3Se2) supported on nickel foam has been fabricated by a hydrothermal reaction followed by a chemical etching process. The unique three-dimensional (3D) interconnected nanowires not only endow Ru and Ni3Se2 with uniform distribution and coupling, but also provide higher electrical conductivity, more active sites, an optimized electronic structure and favorable reaction kinetics. Therefore, the as-obtained Ru/Ni3Se2 catalyst exhibits excellent electrocatalytic performance, with low overpotentials of 24 and 211 mV to supply a current density value of 10 mA cm-2 towards the HER and OER in an alkaline environment, respectively. Notably, the as-fabricated Ru/Ni3Se2 catalyst only requires a low voltage of 1.476 V to derive a current density of 10 mA cm-2 in the constructed two-electrode alkaline electrolyzer and exhibits exceptionally high stability. This work will provide a novel strategy for the design and fabrication of low-cost and high-performance bifunctional electrocatalysts for hydrogen production by water electrolysis.
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Supramolecular electronics provide an opportunity to introduce molecular assemblies into electronic devices through a combination of noncovalent interactions such as [π···π] and hydrogen-bonding interactions. The fidelity and dynamics of noncovalent interactions hold considerable promise when it comes to building devices with controllable and reproducible switching functions. Here, we demonstrate a strategy for building electronically robust switches by harnessing two different noncovalent interactions between a couple of pyridine derivatives. The single-supermolecule switch is turned ON when compressing the junction enabling [π···π] interactions to dominate the transport, while the switch is turned OFF by stretching the junction to form hydrogen-bonded dimers, leading to a dramatic decrease in conductance. The robustness and reproducibility of these single-supermolecule switches were achieved by modulating the junction with Ångström precision at frequencies of up to 190 Hz while obtaining high ON/OFF ratios of â¼600. The research presented herein opens up an avenue for designing robust bistable mechanoresponsive devices which will find applications in the building of integrated circuits for microelectromechanical systems.
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The gut microbiome is clearly linked to the development of various autoimmune diseases, however, its association with immune thrombocytopenia (ITP) is less well understood. The current study collected 73 samples, including 36 from healthy individuals and 37 from ITP patients. The gut microbial community was assessed using 16s rRNA sequencing. Findings illustrated that the abundance of key microbiota was significantly higher in the ITP group. This group was further divided into three subgroups that received different treatments for ITP. A random forest model was used to predict the key microbiota and the identified bacteria were shown to easily distinguish between the healthy and the ITP treatment groups. Microbial function annotation and difference analysis showed that drug treatment changed the gut microbiota and may play a role in inducing host autoimmune responses by changing microbial metabolism pathways. Clinical indices also correlated negatively with changes in the microbiota after treatment. In summary, ITP patients who received drug treatment had significant differences in their microbiota along with a high abundance of bacteria. Thus, the microbiome could be used as a biomarker to distinguish between healthy and ITB groups. The key differential bacteria could help to regulate the number of platelets in ITP patients and provide a red blood cell overstock.
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Microbioma Gastrointestinal , Púrpura Trombocitopénica Idiopática , Humanos , Recuento de Plaquetas , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , ARN Ribosómico 16S/genética , Recuento de EritrocitosRESUMEN
The rapid detection of low concentrations of Salmonella Typhimurium (S. Typhimurium) is an essential preventive measure for food safety and prevention of foodborne illness. The study presented in this paper addresses this critical issue by proposing a single mode-tapered seven core-single mode (STSS) fiber ring laser (FRL) biosensor for S. Typhimurium detection. The experimental results show that the specific detection time of S. Typhimurium is less than 20 min and the wavelength shift can achieve -0.906 nm for an S. Typhimurium solution (10 cells/mL). Furthermore, at a lower concentration of 1 cell/mL applied to the biosensor, a result of -0.183 nm is observed in 9% of samples (1/11), which indicates that the proposed FRL biosensor has the ability to detect 1 cell/mL of S. Typhimurium. In addition, the detection results in chicken and pickled pork samples present an average deviation of -27% and -23%, respectively, from the measured results in phosphate buffered saline. Taken together, these results show the proposed FRL biosensor may have potential applications in the fields of food safety monitoring, medical diagnostics, etc.
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Técnicas Biosensibles , Técnicas Biosensibles/métodos , Salmonella typhimurium , Microbiología de Alimentos , Alimentos , Inocuidad de los AlimentosRESUMEN
PURPOSE: This study was aimed to evaluate the clinical significance and prognostic value of CRP/albumin ratio (CAR) in patients with gastric cancer. METHODS: The data of 205 gastric cancer patients who underwent surgery was analyzed retrospectively. The association of CAR with the clinical features and prognostic value in gastric cancer was analyzed. The data of this study was combined with previous studies to further determine the prognostic value of CAR in patients with gastric cancer using a meta-analysis method. RESULTS: Cox analysis revealed that preoperative CAR was an independent prognosis indicator in patients with gastric cancer. High expression of CAR indicated a shorter survival time than in those with lower expression. CAR has a higher prognostic value in the 1-, 3-, and 5-year overall survival in patients with gastric cancer. CAR showed significant difference regarding the gastric cancer patients' age, M stage, and clinical stage. The discriminate value of CAR in M stage of gastric cancer was high (area under the curve, 0.809). A meta-analysis combining previous data and our data showed that preoperative CAR demonstrated a significant association with the overall survival of patients with gastric cancer. CONCLUSION: This study demonstrated that preoperative CAR could serve as an important prognostic indicator in patients with gastric cancer.
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BACKGROUND: Enterobacter cloacae is an emerging opportunistic pathogen. We retrospectively conducted a study to assess antimicrobial susceptibility and investigated the Molecular characteristics of carbapenem-resistant Enterobacter cloacae (CREL) isolates. METHODS: Three hundred forty-two isolates of Enterobacter cloacae were collected from January 2014 to December 2018. Ten strains of CREL were collected for further research. The species identifications and minimum inhibitory concentrations (MICs) of all antibiotics tested were analyzed using the Vitek 2 Compact system (BioMerieux, France) and supplemented by the disk diffusion method. Polymerase chain reaction (PCR) was performed to detect extended-spectrum ß-lactamase (ESBL) and carbapenemase resistance genes. RESULTS: The results showed that most of the isolates remained susceptible to tested antibiotics; however, the resistance rate of Cefepime has been increasing in recent years. One strain co-producing New Delhi Metallo-ß-lactamase NDM-1 and Imipenem hydrolase IMP-4. NDM-1 and IMP-4-producing isolates highlight that active surveillance is necessary to prevent the further spread of the bacteria. Multilocus sequence typing (MLST) showed that two KPC-producing isolates assigned to ST93, two isolates carrying NDM-1 assigned to ST1120. Moreover, the MEGA analysis showed that ST93, ST256, and ST1120 have homology, showing that CREL in our area has a potential spread risk. CONCLUSIONS: These findings indicating that CREL clonal dissemination may occurred in this region and should be taken seriously concern. Our study highlights an urgent need to monitor these isolates to prevent their further spread.
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Enterobacter cloacae , Infecciones por Enterobacteriaceae , Antibacterianos/uso terapéutico , China , Enterobacter cloacae/genética , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Francia , Humanos , Tipificación de Secuencias Multilocus , Estudios Retrospectivos , beta-Lactamasas/genéticaRESUMEN
This study aimed to investigate the efficacy of colistin both alone and in combination with either meropenem or levofloxacin against CRAB clinical isolates. The OXA carbapenemase genes and multilocus sequence typing were detected after 35 CRAB isolates biochemical identification. Then, the minimum inhibitory concentrations, minimum bactericidal concentrations, antibiotic interactions of the test antibiotics, and synergistic effects were determined by the checkerboard method and time-kill assays. The chromosomal gene bla OXA-51-like was detected in all isolates, and bla OXA-23-like and bla OXA-24-like were present in 91.4% and 25.7% of the isolates, respectively. The combination of colistin and meropenem displayed the highest rate of synergy (51.4%) against the 35 isolates, while the colistin-levofloxacin combination showed a higher rate of indifference interaction (22.9%) than that of the colistin-meropenem (8.6%) combination. The synergistic effect of colistin against the CRAB isolates was confirmed. The combination of colistin with meropenem is recommended against CRAB isolates.
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Acinetobacter baumannii/efectos de los fármacos , Antibacterianos/farmacología , Colistina/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Antibacterianos/administración & dosificación , Carbapenémicos/farmacología , Colistina/administración & dosificación , Sinergismo Farmacológico , Quimioterapia Combinada , Humanos , Levofloxacino/farmacología , Meropenem/farmacología , Pruebas de Sensibilidad MicrobianaRESUMEN
BACKGROUND: This study will be designed to appraise the effects of intraoperative pressure ulcer preventive nursing (IPUPN) on inflammatory markers (IMs) in patients with high-risk pressure ulcers (HRPU) based on high quality randomized controlled trials (RCTs). METHODS: In this study, we will perform a rigorous literature search from the following electronic databases: Cochrane Library, MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, and Chinese Biomedical Literature Database. All electronic databases will be retrieved from their initial time to March 1, 2020 without limitations of language and publication status. We will only consider high quality RCTs that explored the effects of IPUPN on IMs in patients with HRPU. Two investigators will identify relevant trials, extract data, and appraise risk of bias in each eligible trial. Data will be pooled by either a fixed-effects model or a random-effects model according to the results of heterogeneity identification. The primary outcomes include IMs, and incidence of new pressure ulcers. The secondary outcomes are time to ulcer development, quality of life, length of hospital stay, and adverse events. Statistical analysis will be undertaken using RevMan 5.3 software. RESULTS: This study will summarize high quality clinical evidence of RCTs to evaluate the effects of IPUPN on IMs in patients with HRPU. CONCLUSION: The expected findings may provide helpful evidence to determine whether IPUPN is an effective intervention on IMs in patients with HRPU. INPLASY REGISTRATION NUMBER: INPLASY202040029.
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Biomarcadores/análisis , Inflamación/sangre , Úlcera por Presión/prevención & control , Biomarcadores/sangre , Protocolos Clínicos , Humanos , Inflamación/fisiopatología , Complicaciones Intraoperatorias/enfermería , Complicaciones Intraoperatorias/prevención & control , Metaanálisis como Asunto , Úlcera por Presión/enfermeríaRESUMEN
Graphene membranes with subnanopores are considered to be the next-generation materials for water desalination and ion separation, while their performance is mainly determined by the relative ion selectivity of the pores. However, the origin of this phenomenon has been controversial in the past few years, which strongly limits the development of related applications. Here, using direct Au ion bombardment, we fabricated the desired subnanopores with average diameters of 0.8 ± 0.16 nm in monolayer graphene. The pores showed the ability to sieve K+, Na+, Li+, Cs+, Mg2+, and Ca2+ cations, and the observed K+/Mg2+ selectivity ratio was over 4. With further molecular dynamics simulations, we demonstrated that the ion selectivity is primarily attributed to the dehydration process of ions that can be quantitatively described by the ion-dependent free-energy barriers. Hopefully, this work is helpful in further enhancing the ion selectivity of graphene nanopores and also presenting a new paradigm for improving the performance of other nanoporous atomically thin membranes, such as MXenes and MoS2.
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Nanopore devices are applied in many fields such as molecular sensing and DNA sequencing, and the detection precision is primarily determined by 1/f noise. The mechanism of 1/f noise in nanopores is still not clearly understood, especially the nonequilibrium 1/f noise in rectifying nanopores. Hereby, we propose that 1/f noise in solid-state nanopores originates from the electrolyte ion trapping-detrapping process occurring on the inner surface of the nanopores, which can nonlinearly affect the ion number inside the rectifying nanopores due to the specific ion enrichment/depletion effect. Our model can not only quantitatively explain the nonlinear dependence of 1/f noise on the applied voltage, i.e., the nonequilibrium 1/f noise, for current rectifying nanopores, but also provide a unified explanation on the influence of the electrolyte concentration, pH value, and geometry of the nanopores. From our model, we observe a new flattening phenomenon of 1/f noise in conical nanopores, and this is further confirmed by our experimental results. Our research can be helpful in understanding and reducing 1/f noise in other nanopore devices, especially where the enrichment or depletion of ions exists.
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BACKGROUND: There is increasing resistance to carbapenems among Klebsiella pneumoniae,and fluoroquinolones (FQ) are increasingly used to treat infections from extended-spectrum ß- lactamase(ESBLs) and carbapenemase-producing Klebsiella pneumoniae. However, the acquisition of plasmid-mediated quinolone resistance (PMQR) or the spontaneous mutation of the quinolone resistance-determining regions (QRDR) of the gyrA and parC genes can severely affect the therapeutic effect of quinolones. The goal of this study was to investigate the molecular determinants of FQ resistance(FQ-R) in carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates from Heilongjiang Province,China. MATERIALS AND METHODS: We isolated 40 strains of CRKP from a treatment center in the eastern part of Heilongjiang Province from January 2016 to December 2018. The VITEK2 Compact analyzer was used to identify and detect drug sensitivity. Different types of drug resistance genes were detected by polymerase chain reaction (PCR). PCR and DNA sequencing were used to assess the presence of qnrA, qnrB, qnrS,qepA and acc(6') Ib-cr genes,which are plasmid-encode genes that can contribute to resistance. The sequences of gyrA and parC genes were sequenced and compared with the sequences of standard strains to determine if mutations were present.Multi-site sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were performed on the strains to assess homology. RESULTS: The isolated CRKP strains showed rates of resistance to fluoroquinolones of 22.5% to 42.5%. The resistance rate of ciprofloxacin was significantly higher than that of levofloxacin.Nine CRKP strains (22.5%) showed co-resistance to ciprofloxacin and levofloxacin.The quinolone resistant strains were screened for plasmid-encoded genes that can contribute to resistance (PMQR genes).Among the 17 quinolone resistant strains,one strain contained no PMQR genes,twelve strains contained two PMQR genes,and four strains contained four PMQR genes.Acc (6') Ib-cr was the most frequently detected PMQR gene, detected in 95% of strains tested (38 of 40) and in 94.1% of the quinolone-resistant strains (16 of 17). The qepA gene encoding an efflux pump was not detected in any strains.No isolate carried five different PMQRs simultaneously.Changes of S83I and D87G changes in gyrA, and the S80I change in parC,which were mediated by QRDR,were identified in two isolates,which showed resistance to both ciprofloxacin and levofloxacin.Most of the FQ-R strains(58.8%,10/17) belong to ST(sequence type) 76, which is dominant in the local area, while all the mutant strains (100%,2/2),that differ in at least one site from standard bacteria, belong to the ST11 group. The strains were isolated from a hospital where there had been a recent outbreak of ST76 type CRKP in the neurosurgery ward and intensive care unit. CONCLUSION: CRKP strains were identified that were insensitive or even resistant to quinolones,and this resistance is common in Heilongjiang Province of eastern China;fluoroquinolone-resistance in these clinical CRKP strains is a complex interplay between PMQR determinants and mutations in gyrA and parC.The resistance level caused by QRDR mutation is higher than that caused by PMQR, however, the high frequency of PMQR genes in the isolated CRKP strains suggests the potential for impact of these genes.PMQR determinants are often found in carbapenemase-producing or ESBLs-producing Klebsiella pneumoniae,and some resistance genes,such as:SHV,TEM, CTX-M-15,and OXA-1 are closely associated with FQ-R. Finally, geographical factors can affect the emergence and spread of PMQR and QRDR.Some genetic lineages have higher potential risks, and continuous close monitoring is required.
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Antibacterianos/farmacología , Girasa de ADN/genética , Topoisomerasa de ADN IV/genética , Farmacorresistencia Bacteriana/genética , Klebsiella pneumoniae/genética , Anciano , Proteínas Bacterianas/genética , Carbapenémicos/farmacología , China , Farmacorresistencia Bacteriana/efectos de los fármacos , Femenino , Humanos , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/aislamiento & purificación , Masculino , Pruebas de Sensibilidad Microbiana , Plásmidos , Prevalencia , Quinolonas/farmacologíaRESUMEN
BACKGROUND: Enterobacter cloacae complex (ECC) is one of the most common extended-spectrum ß-lactamase and carbapenemase-producing pathogen that threatens millions of the elderly and vulnerable sick persons. The objective of this study was to perform the molecular characteristics of the carbapenem-resistant E. cloacae complex (CREC) emerged in Heilongjiang Province of China. METHODS: Six CREC strains were isolated from the patients with infectious diseases. The identities of ECC isolates were confirmed by sequencing the polymerase chain reaction (PCR) products of 16S rRNA gene. The characterization of the CREC isolates were analyzed by sequencing PCR products of the carbapenemase, ampC and fluoroquinolone resistance genes and performing multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE) and whole genome sequencing. RESULTS: All 6 isolates harbored multiple resistance genes. Of them, 5 carried metallo-ß-lactamases and one was blaKPC-2-positive. The levofloxacin and ciprofloxacin-resistant strains had substitutions of gyrA83, gyrA87, and parC80 in the quinolone-resistance determining regions. The MLST analyses revealed that 6 isolates belonged to five sequence types (ST520, ST528, ST1119, ST1120, and ST93) while the PFGE patterns of the isolates fallen into four clusters. The strain ST1120 was found to carry two separated plasmids that encode blaNDM-1 and blaIMP-4. CONCLUSIONS: Our study, for the first time, identified a CREC strain that co-produces blaNDM-1 and blaIMP-4 in the Northeast China. Our finding emphasizes an urgent need for more intensive surveillance and precaution measures to prevent the CERC spread.
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Enterobacteriaceae Resistentes a los Carbapenémicos/genética , Farmacorresistencia Bacteriana/genética , Enterobacter cloacae/efectos de los fármacos , Enterobacter cloacae/genética , beta-Lactamasas/genética , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Técnicas de Tipificación Bacteriana , Enterobacteriaceae Resistentes a los Carbapenémicos/aislamiento & purificación , China , Farmacorresistencia Bacteriana/efectos de los fármacos , Enterobacter cloacae/clasificación , Enterobacter cloacae/aislamiento & purificación , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Infecciones por Enterobacteriaceae/microbiología , Fluoroquinolonas/farmacología , Humanos , Tipificación de Secuencias Multilocus , ARN Ribosómico 16SRESUMEN
BACKGROUND: Selecting alternative antibiotic combinations as treatment options may help successfully manage carbapenem-resistant Acinetobacter baumannii (CRAB). This study aimed to determine the synergistic effects of tigecycline (TIG) monotherapy versus combination therapy with other antimicrobials against CRAB. METHODS: After performing biochemical identification assays, we detected oxacillin-hydrolyzing (OXA)-type carbapenemase genes in 35 CRAB isolates. The minimum inhibitory concentrations (MICs) and interactions of the test drugs were determined using the checkerboard assay with TIG, colistin (CST) and meropenem (MEM). Static time-kill assays were conducted to validate the synergistic effects of the most efficacious combination. RESULTS: The chromosomal gene, blaOXA-51-like, was tested among all isolates, blaOXA-23-like and blaOXA-24-like were present in 91.4% and 25.7%, respectively. In the checkerboard assay, the combination of TIG and MEM displayed the highest rate of synergy (30.5%) against the 35 isolates. In contrast, the TIG-CST combination showed a higher indifference interaction rate (36.1%) than that of the TIG-MEM (16.7%) combination. Antagonism appeared in one isolate for the TIG-CST combinations. The static time-kill assays confirmed the superior synergistic effect of CST against the CRAB isolates. CONCLUSIONS: TIG combined with CST exhibited early synergistic activity that was not sustained beyond 12 h. TIG combination therapy can only be recommended when other optimized therapeutics are unavailable.
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Acinetobacter baumannii/efectos de los fármacos , Antibacterianos/uso terapéutico , Farmacorresistencia Microbiana/efectos de los fármacos , Tigeciclina/uso terapéutico , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , China , Humanos , Pruebas de Sensibilidad Microbiana , Tigeciclina/administración & dosificación , Tigeciclina/farmacologíaRESUMEN
BACKGROUND: To investigate the activity of 5 antibiotic monotherapies, including colistin (COL), meropenem (MEM), amikacin (AMK), levofloxacin (LEV), and tigecycline (TGC), when combined with 4 other antibiotics against clinical isolates of carbapenem-resistant Klebsiella pneumoniae (CRKP) in vitro. METHODS: The minimum inhibitory concentrations (MICs) of 5 antibiotics against 40 CRKP isolates were determined by micro-broth dilution method. There were synergistic effects between TGC combinations in the 10 CRKP isolates detected with checkerboard microdilution method. Time-kill assay was used to assess the monotherapies and the TGC combinations against 4 distinct sequence typing (STs) CRKP isolates. Polymerase chain reaction (PCR) tests were used to detect the carbapenemase genes, extended-spectrum beta lactamase (ESBL) genes, colistin resistance gene, and quinolone resistance genes, while multilocus sequence typing (MLST) was performed for 10 CRKP isolates. RESULTS: The MICs of TGC, COL, MEM, AMK, and LEV were 0.5-2, 2-32, 4-256, 1-16,384, and 0.5-64 µg/mL, respectively. The combinations exerted a significant synergism or additive effect via the checkerboard technique for most tested CRKP isolates, but a portion of the CRKP isolates had an indifferent effect except for the TGC-AMK combination. In addition, time-kill assays revealed that TGC enhanced the bactericidal activity of the 4 other antibiotics. Among 10 CRKP isolates, blaKPC-2 (90%), blaSHV (100%), and blaacc(6')-Ib (100%) were the most common carbapenemase genes, ESBL genes, and quinolone resistance genes, respectively. ST76 (70%) was the most predominant clone, followed by ST11 (10%), ST375 (10%), and ST530 (10%). CONCLUSIONS: In contrast to the currently recommended TGC therapy, our in vitro data suggest that TGC combinations may be a valid therapeutic option against CRKP, even in the presence of 1 antibiotic resistant isolate in TGC combination therapy. TGC-AMK combination is a cost-effective option for treating CRKP in the eastern region of Heilongjiang Province. In addition, TGC combinations might circumvent the overuse of carbapenems during the era of multi-drug resistance in Klebsiella pneumoniae (KP).
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Antibacterianos/farmacología , Enterobacteriaceae Resistentes a los Carbapenémicos/efectos de los fármacos , Klebsiella pneumoniae/efectos de los fármacos , Tigeciclina/farmacología , Antibacterianos/administración & dosificación , Humanos , Pruebas de Sensibilidad Microbiana , Tigeciclina/administración & dosificaciónRESUMEN
BACKGROUND: The prognostic value of C-reactive protein/albumin ratio (CAR) in pancreatic cancer remains controversial. This study aimed to determine the potential role of CAR as a prognostic indicator in pancreatic cancer. METHODS: A comprehensive literature search up to December 2018 was conducted using PubMed, Web of Science, and other databases. The hazard ratio (HR) with 95% confidence interval (CI) was employed to quantitatively assess CAR as a prognostic indicator in patients with pancreatic cancer. RESULTS: Eleven studies with 2047 pancreatic cancer patients were selected for the analysis. Ten out of 11 studies included only Asian patients. The pooled results showed that a higher CAR value was significantly associated with a poor overall survival of pancreatic cancer patients (random-effects model: HRâ=â1.86; 95% CIâ=â1.53-2.26). Sensitivity analysis indicated the stability of the overall pooled results. Subgroup analysis and meta-regression analysis revealed that the country under study, cut-off value of CAR, treatment of patients, and the period of follow-up did not affect the prognostic value of CAR in pancreatic cancer patients (Pâ>â.05). No publication bias was noted across the studies (Pâ=â.933). CONCLUSION: This meta-analysis suggests that CAR is associated with the survival of pancreatic cancer patients of Asian ethnicity, and a higher CAR may be a potential prognostic indicator in pancreatic cancers.
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Proteína C-Reactiva/análisis , Neoplasias Pancreáticas , Albúmina Sérica/análisis , Pueblo Asiatico , Humanos , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/etnología , Neoplasias Pancreáticas/mortalidad , Valor Predictivo de las Pruebas , PronósticoRESUMEN
Postoperative peritoneal adhesions (PPAs) constitute a common complication of abdominal surgery with a high incidence. Bletilla striata (BS) is an important hemostatic drug used in China for nearly 2000 years. The purpose of this study was to investigate the effect of Bletilla striata on postoperative intestinal adhesion in rats. PPA was induced by cecal wall abrasion, and Bletilla striata was injected to observe its effect on adhesion in rats. The adhesion and inflammation score were assessed through visual observation and histopathologic evaluation. The levels of interleukin-1 (IL-1ß), tumor necrosis factor (TNF-α), and interleukin-17F (IL-17F) in abdominal cavity and interleukin-6 (IL-6) in plasma were measured by enzyme-linked immunosorbent assay (ELISA) at 6 hours, 12 hours, 24 hours, and 1 week after operation. The tissue level of transforming growth factor beta-1 (TGF-ß1) was also determined by ELISA on the seventh day after surgery. The expressions of collagen and TNF-α were, respectively, detected by Masson trichrome staining and immunohistochemical staining. The expression of TGF-ß1 and alpha smooth muscle actin (α-SMA) was detected by Western blot. The result showed that Bletilla striata has obvious preventive effect on PPAs and celiac inflammation of PPAs. Bletilla striata could significantly reduce the level of IL-17F abdominal cavity and IL-6 in plasma. Masson trichrome staining and immunohistochemical staining results showed that Bletilla striata also decreased the expression of TNF-α and collagen. Western blot results showed that Bletilla striata decreased the expression of α-SMA and TGF-ß1. Our results suggest that Bletilla striata decreased the development of abdominal adhesion in abrasion-induced model of rats and reduced the expression of the important substance which increased in PPAs. Bletilla striata can be further studied as a new and cheaper antiadhesive substance.
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Presently, data on the type 2 diabetes mellitus (T2DM) in Chinese Korean ethnicity are very scarce. This study aimed to explore the relationship between the transcription factor 7-like 2 (TCF7L2) and T2DM in Chinese Korean ethnicity population. This case-control study involved 43 T2DM Chinese Korean ethnicity patients (T2DM group) and 43 healthy Chinese Korean ethnicity normoglycemic subjects as controls (Control group). All included participants aged from 40 to 75 years old. Clinical and biological data were collected to determine the phenotypic traits. The restriction fragment length polymorphism-polymerase chain reaction was used to analyze the TCF7L2 by genotyping for rs7903146 (C/T). Spectrophotometer with Chronolab kits was used to conduct the biochemical analyses. TCF7L2 was associated with T2DM in the Chinese Korean ethnicity population (Pâ<â.01 for alleles, and Pâ<â.05 for genotypes). Significant differences were found 2 groups regarding the T allele (37.2% T2DM patients vs 15.1% healthy subjects, Pâ<â.01), and G allele (62.8% T2DM patients vs 84.9% healthy subjects, Pâ<â.01). The risk genotypes were GG (83.7% T2DM patients, vs 44.2% healthy control, Pâ<â.01), GT (4.7% T2DM patients, vs 20.9% healthy control, Pâ=â.04), and TT (11.6% T2DM patients, vs 34.9% healthy control, Pâ=â.01). The results of this study demonstrated that TCF7L2 is associated with T2DM in the Chinese Korean ethnicity population, which is an important risk factor for T2DM in this population.
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Pueblo Asiatico/genética , Diabetes Mellitus Tipo 2/etnología , Diabetes Mellitus Tipo 2/genética , Polimorfismo Genético/genética , Proteína 2 Similar al Factor de Transcripción 7/genética , Adulto , Anciano , Estudios de Casos y Controles , China , Femenino , Humanos , Corea (Geográfico)/etnología , Masculino , Persona de Mediana EdadRESUMEN
The purpose of this study was to investigate the synergistic and bactericidal effects of combinations of colistin with meropenem or amikacin in vitro and provide laboratory data needed for development of therapeutic strategies for the treatment of carbapenem-resistant Klebsiella pneumoniae (CRKP) infection. We found that minimum inhibitory concentration (MIC) of colistin, meropenem and amikacin were 2~32, 4~256, and 1~16384 µg/ml, respectively. The minimum bactericidal concentration of the antibiotics was either 1× or 2×MIC. Treatments of 6 CRKP isolates at 1 µg/ml colistin completely killed 2 of them and suppressed 4 others growth. 4 CRKP isolates at 16 µg/ml meropenem or amikacin completely killed and suppressed 2 others growth. 2 CRKP isolates showed synergic effects in all colistin combination and 3 CRKP isolates showed synergic effects in part of colistin combination. Our data suggest that colistin in combination with either meropenem or amikacin could be a valid therapeutic option against colistin-resistant CRKP isolates. Moreover, the combination of colistin-amikacin is less expensive to treat CRKP infections in Eastern Heilongjiang Province.
Asunto(s)
Amicacina/farmacología , Antibacterianos/farmacología , Enterobacteriaceae Resistentes a los Carbapenémicos/efectos de los fármacos , Colistina/farmacología , Meropenem/farmacología , Amicacina/uso terapéutico , Antibacterianos/uso terapéutico , Enterobacteriaceae Resistentes a los Carbapenémicos/clasificación , Enterobacteriaceae Resistentes a los Carbapenémicos/genética , Colistina/uso terapéutico , Farmacorresistencia Bacteriana Múltiple , Sinergismo Farmacológico , Quimioterapia Combinada , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Infecciones por Enterobacteriaceae/microbiología , Humanos , Meropenem/uso terapéutico , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias MultilocusRESUMEN
BACKGROUND: The emergence of carbapenem-resistant Enterobacteriaceae (CRE) has become a significant problem for global public health. Currently, treatments program is minimal. This study aimed to evaluate the molecular mechanisms of carbapenem-resistant Enterobacter cloacae complex isolates (CREC) infections. Methods: Resistance genes were detected using PCR with specific primers. Multilocus sequence typing (MLST) was also performed. Furthermore, we evaluated the effects of polymyxin B (PMB) and tigecycline (TGC) antibiotics (Abs) alone and in combination with meropenem (MEM), amikacin (AMK), and levofloxacin (LEV) against CREC isolates. The results were then compared with in vitro synergy testing results obtained from time-kill assays (TKAs), and the microdilution checkerboard method. RESULTS: The synergistic efficiency of PMB + TGC was also evaluated. Abs use clinically achievable concentrations to determine the antibacterial effects of the Ab. Similar sequence type (ST) classifications had a comparably resistant phenotype; PMB-based combination therapy is better than TGC-based combination therapy. CONCLUSIONS: we found that the combination of PMB + AMK is promising for the treatment of AMK-sensitive CREC. The high-risk ST93 carrying the bla KPC-2 gene should be monitored.