Anti-atopic dermatitis effect of fraxinellone via inhibiting IL-31 in vivo and in vitro.

Chronic recurrent itch and skin inflammation are prominent features of atopic dermatitis (AD), which is closely related to the immune response driven by T-helper type 2 (Th2) cells. The expression of interleukin 31 (IL-31) is positively correlated with the severity of dermatitis. Anti-IL-31 receptor α (IL-31RA) targeted drugs have been used to treat AD, however, they are expensive and have side effects. Fraxinellone (FRA) is one of the main limonoid components in the dried root bark of Dictamnus dasycarpus Turcz.; however, its anti-inflammatory and antipruritic effects on atopic dermatitis (AD) have not been previously reported. In this study, we investigated the anti-dermatitis effect of FRA and its potential mechanism of action using a 2,4-dinitrofluorobenzene (DNFB)-induced AD-like mouse model and lipopolysaccharide (LPS)-stimulated HaCaT cells. FRA significantly inhibited chronic pruritus, epidermal thickening, and inflammatory infiltration in AD mice. FRA not only inhibited the levels of IL-31 in the serum and lesioned skin of AD mice but also significantly downregulated the mRNA expression and protein levels of IL-31, IL-31RA, transient receptor potential (TRP) V1, and TRPA1 in the lesioned skin and dorsal root ganglion (DRG) of AD mice. In LPS-stimulated HaCaT cells, FRA inhibited the production of iNOS and COX2, as well as the protein levels of IL-31, IL-31RA, TRPV1 and TRPA1, showing significant anti-inflammatory effects. In summary, our findings suggest that FRA exerts antipruritic and anti-inflammatory effects in AD by regulating the IL-31 pathway, and may hold promise for the clinical treatment of AD.

Thromboelastography-Guided Antiplatelet Therapy for Patients with Ischemic Cerebrocardiovascular Diseases: A Systematic Review and Meta-Analysis.

INTRODUCTION: The effectiveness of thromboelastography (TEG)-guided antiplatelet therapy in patients with ischemic cerebrocardiovascular diseases is not well-established. This systematic review evaluates the efficacy and safety of TEG-guided antiplatelet therapy compared to standard treatment in patients with ischemic cerebrocardiovascular diseases. METHODS: Randomized controlled trials (RCTs) and observational studies comparing TEG-guided antiplatelet therapy with standard therapy in patients suffering from ischemic stroke (IS) or coronary artery disease (CAD) were identified. The primary efficacy measure was a composite of ischemic and hemorrhagic events. Secondary efficacy measures included any ischemic events, while safety was assessed by the occurrence of bleeding events. RESULTS: Ten studies involving 4 RCTs and 6 observational studies with a total of 1,678 patients were included. When considering a composite of ischemic and hemorrhagic events in RCTs, a significant reduction was observed in IS or CAD patients under TEG-guided therapy compared to standard therapy (OR: 0.45, 95% CI: 0.27-0.75, p = 0.002). After pooling RCTs and observational studies together, compared to standard antiplatelet therapy, TEG-guided therapy significantly reduced the risk of a composite of ischemic and hemorrhagic events (OR: 0.26, 95% CI: 0.19-0.37; p < 0.00001), ischemic events (OR: 0.28, 95% CI: 0.19-0.41; p < 0.00001), and bleeding events (OR: 0.31, 95% CI: 0.16-0.62; p = 0.0009) in patients with IS or CAD. CONCLUSION: TEG-guided antiplatelet therapy appears to be both effective and safe for patients with IS or CAD. These findings support the use of TEG testing to tailor antiplatelet therapy in individuals with ischemic cerebrocardiovascular diseases.

Dual antiplatelet therapy for ischemic stroke with intracranial arterial stenosis: a systematic review and meta-analysis.

Background: The safety and efficacy of dual antiplatelet therapy (DAPT) in ischemic stroke patients with intracranial artery stenosis (ICAS) remain contentious. Aims: This study evaluates DAPT's effectiveness and safety for these patients. Methods: This review was reported following PRISMA 2020 guidelines. A comprehensive search was conducted in PubMed, Embase, Cochrane Library, ClinicalTrials.gov, CNKI, WanFang, VIP, and SinoMed up to June 20, 2023, for randomized controlled trials comparing efficacy and safety of DAPT against single antiplatelet therapy (SAPT) in ischemic stroke patients with ICAS. The primary outcome was a composite of ischemic and bleeding events. Secondary outcomes included stroke (cerebral infarction and hemorrhage), ischemic events, and cerebral infarction. Safety outcomes assessed were bleeding events, cerebral hemorrhage, and mortality. Risk ratios (RRs) with 95% confidence intervals (CIs) were synthesized using Review Manager 5.4. Results: Analysis of 21 randomized controlled trials involving 3,591 patients revealed that DAPT significantly lowered the rate of ischemic and bleeding events (RR = 0.52; 95% CI: 0.46-0.59, p < 0.001) and recurrent stroke (RR = 0.37; 95% CI: 0.30-0.44, p < 0.001) compared to SAPT. There was no significant increase in bleeding events (RR = 1.34; 95% CI: 0.97-1.85, p = 0.07) or cerebral hemorrhage (RR = 0.47; 95% CI: 0.17-1.31, p = 0.15). Conclusion: DAPT proveed to be effective and safe for ischemic stroke patients with ICAS and significantly reduced stroke and the composite endpoint of ischemic and bleeding events without elevating bleeding risks.

Protective effect of exosomes derived from bone marrow mesenchymal stem cells on hypoxia reperfusion injury of cardiomyocytes.

We aimed to investigate the cardiomyocyte-protective effects of bone marrow mesenchymal stem cells (BMSCs)-derived exosomes on ischemia/reperfusion (I/R)-injured rats and to explore the mechanisms. Cardiomyocytes were divided into control group, ischemia/reperfusion group (I/R group), ischemia/reperfusion+exosome group (I/R+Exo group) or ischemia/reperfusion+exosomes transfected with miR-101a-3p inhibitor group (I/R+Exo inhibitor group). MiR-101a-3p levels were lower in I/R and I/R+Exo inhibitor groups than in control and I/R+Exo groups. Apoptosis rate and cleaved caspase 3 expression were higher in I/R and I/R+Exo inhibitor groups. The levels of superoxide dismutase (SOD) in cardiomyocytes of I/R group and I/R+Exo inhibitor group were lower than those of control group and I/R+Exo group, and the levels of malondialdehyde (MDA) and the relative production of oxygen species clusters (ROS) in cardiomyocytes of I/R group and I/R+Exo inhibitor group were higher than those of control group and I/R+Exo group. The levels of interleukin-10 (IL-10), interleukin-6 (IL-6), tumour necrosis factor α (TNF-α), and nuclear factor κB (NF-κB) were higher in the I/R group and the I/R +Exo inhibitor group than in the control group and the I/R+Exo group. Bioinformatics analysis suggested that Pik3c3 is the most promising gene involved in miR-101a-3p-mediated apoptosis in cardiomyocytes, and in vitro experiments confirmed that low expression of miR-101a-3p significantly up-regulated the mRNA and protein expression levels of Pik3c3. BMSCs-derived exosomes have a protective effect on cardiomyocytes from I/R-injured rats, and the mechanism may be related to the inhibition of oxidative stress and inflammatory responses in cardiomyocytes by exosome-delivered miR-101a-3p.

A Mouse Ear Model for Allergic Contact Dermatitis Evaluation.

Skin is the human body's first line of defense and one of the most exposed organs to environmental chemicals. Allergic contact dermatitis (ACD) is a common skin disease that manifests as a local rash, redness, and skin lesions. The occurrence and development of ACD are influenced by both genetic and environmental factors. Although many scholars have constructed a series of models of ACD in recent years, the experimental protocols of these models are all different, which makes it difficult for readers to establish them well. Therefore, a stable and efficient animal model is of great significance to further study the pathogenesis of atopic dermatitis. In this study, we detail a modeling method using 1-fluoro-2,4-dinitrobenzene (DNFB) to induce ACD-like symptoms in the ears of mice and describe several methods for assessing the severity of dermatitis during modeling. This experimental protocol has been successfully applied in some experiments and has a certain promotional role in the field of ACD research.

Protective effect of bone marrow mesenchymal stem cell-derived exosomes on cardiomyoblast hypoxia-reperfusion injury through the HAND2-AS1/miR-17-5p/Mfn2 axis.

BACKGROUND: The exosomes (exos) of bone marrow mesenchymal stem cells (BMSCs) play an important therapeutic role in repairing myocardial injury. The purpose of this study was to explore how the exos of BMSCs can alleviate the myocardial cell injury caused by hypoxia/reoxygenation (H/R) through HAND2-AS1/miR-17-5p/Mfn 2 pathway. METHODS: Cardiomyocytes H9c2 were damaged by H/R to mimic myocardial damage. Exos were gained from BMSC. The content of HAND2-AS1 and miR-17-5p was assessed by RT-qPCR. Cell survival rate and apoptosis were estimated by MTT assay and flow cytometry. Western blotting was used to detect the expression of protein. The contents of LDH, SOD, and MDA in the cell culture were detected by commercial kits. The luciferase reporter gene method confirmed the targeted relationships. RESULTS: In H9c2 cells induced by H/R, the level of HAND2-AS1 declined and the expression of miR-17-5p was elevated, but their expression was reversed after exo treatment. Exos improved the cell viability, declined cell apoptosis, controlled the oxidative stress, and repressed inflammation, thus attenuating the damage of H9c2 induced by H/R, whereas, the knockdown of HAND2-AS1 partly alleviated the impacts of exos. MiR-17-5p played the opposite role to HAND2-AS1 on H/R-injured myocardial cells. CONCLUSION: Exos derived from BMSC could alleviate H/R-induced myocardial injury by activating HAND2-AS1/miR-17-5p/Mfn2 pathway.

Syringin exerts anti-inflammatory and antioxidant effects by regulating SIRT1 signaling in rat and cell models of acute myocardial infarction.

INTRODUCTION: This study aimed to investigate the role of syringin in improving heart function during myocardial ischemia/reperfusion (I/R) and to determine whether the sirtuin 1/peroxisome proliferator-activated receptor gamma coactivator 1 alpha (SIRT1/PGC-1α) pathway contributes to this cardioprotective effect in vivo and in vitro. METHODS: H9c2 cells were incubated with H2 O2 for 12 h. The effect of syringin was assessed by measuring cell viability; the apoptotic rate; Keap1/NRF2/HO-1 activation; and the levels of proinflammatory cytokines, oxidative products, and antioxidative enzymes. In addition, SIRT1 was silenced via short hairpin RNA (shRNA)-SIRT1 transfection to evaluate its involvement in syringin-mediated protection. Syringin rescued cells from H2 O2 -induced reductions in viability, antioxidative enzyme levels, and NRF2/HO-1 activation; likewise, syringin inhibited apoptosis, inflammation, and oxidative stress. We also created a rat model of I/R by ligating the left anterior descending coronary artery for 30 min, followed by reperfusion for 12 min. Syringin was then intraperitoneally injected, and the effect on infarct size and cardiac function was examined after 7 days. NRF2/HO-1 activity and the levels of myocardial proinflammatory cytokines, oxidative products, and antioxidative enzymes were measured. RESULTS: In comparison to the untreated I/R group, the syringin treatment group exhibited improved cardiac function and reduced cardiac lesion and infarct size. Syringin administration also markedly reduced the levels of proinflammatory cytokines and reactive oxygen species and promoted antioxidative enzyme expression and NRF2/HO-1 pathway activation. CONCLUSIONS: Syringin may serve a protective role in animal and cell models of I/R by improving cardiac function, inhibiting the inflammatory response, and activating the antioxidative response.

Network pharmacology-based analysis to explore the therapeutic mechanism of Cortex Dictamni on atopic dermatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Dermatitis is a common clinical chronic inflammatory skin disease, which incidence has been on the rise in recent years. It not only seriously affects the physical and mental health of patients but also increase economic burden. Currently, commonly used drugs such as corticosteroids, anti-histamines have certain side effects or are expensive. Therefore, the search for an alternative therapy for dermatitis has important clinical significance. Cortex Dictamni is a commonly used traditional Chinese medicine for expelling wind and itching, but its mechanism for treating dermatitis is still unclear. MATERIALS AND METHODS: Network pharmacological analysis was performed to predict the potential targets and pathways of Cortex Dictamni against dermatitis. Molecular docking was used to assess the binding affinity of active compounds and core targets. By repeatedly stimulating the ears with 1-fluoro-2,4-dinitrobenzene (DNFB), an atopic dermatitis (AD) mouse model was established in order to study the anti-dermatitis effect of Cortex Dictamni. The skin thickness and inflammatory cell infiltration in mouse ears were assessed by tissue staining and flow cytometric. The levels of inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA), and the total protein and phosphorylation levels of related pathways were analyzed by western blotting. RESULTS: In this study, 11 active ingredients, 122 Cortex Dictamni and dermatitis intersection targets were identified. The results from Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the core targets were mainly enriched in immune response and inflammatory signaling pathways. AD mice treated with ethanol extract of Cortex Dictamni (ECD) improved the symptoms of ear skin lesions, alleviated epidermis and dermis thickening of the AD mice ears, decreased pathological immune cell infiltration and attenuated the levels of inflammatory cytokines (TLR4, IL-6, IL-17), and inhibited the hyperactivation of the PI3K-AKT, JAK1-STAT3/STAT6 signal pathways. CONCLUSIONS: Cortex Dictamni can improve the symptoms of skin lesions and the degree of inflammation caused by AD, and may inhibit AD through multiple pathways, such as regulating PI3K-AKT and JAK1-STAT3/STAT6 pathways. These results not only provide experimental evidence for the clinical application of Cortex Dictamni but also provide some help for the research and development of dermatitis drugs.

Dictamnine ameliorates chronic itch in DNFB-induced atopic dermatitis mice via inhibiting MrgprA3.

Chronic itch is the most prominent feature of atopic dermatitis (AD), and antihistamine treatment is often less effective in reducing clinical pruritus severity in AD. Multiple studies have shown that histamine-independent itch pathway is thought to predominate in AD-induced chronic itch. Mas-related G-protein-coupled receptor (Mrgpr) A3+ sensory neurons have been identified as one of the major itch-sensing neuron populations, and transient receptor potential (TRP) channel A1 is the key downstream of MrgprA3-mediated histamine-independent itch. MrgprA3-TRPA1 signal pathway is necessary for the development of chronic itch and may be the potentially promising target of chronic itch in AD. Dictamnine is one of the main quinoline alkaloid components of Cortex Dictamni (a traditional Chinese medicine widely used in clinical treatment of skin diseases). However, the anti-inflammatory and anti-pruritic effect of dictamnine on AD have not been reported. In this study, we used the 2,4-dinitrofluorobenzene (DNFB)-induced AD mouse model to observe the scratching behavior, inflammatory manifestations, and to detect the expression of MrgprA3 and TRPA1 in skin and DRG. The data demonstrated that dictamnine effectively inhibited AD-induced chronic itch, inflammation symptoms, epidermal thickening, inflammatory cell infiltration, and downregulated the expression of MrgprA3 and TRPA1. Furthermore, dictamnine restrained the excitability of MrgprA3+ and TRPA1+ neurons. Molecular docking also indicated that dictamnine has better binding affinity with MrgprA3. These results suggest that dictamnine may inhibit chronic itch caused by AD through the MrgprA3-TRPA1 mediated histamine-independent itch pathway, and may have a potential utility in AD treatment.

MicroRNA-489 Promotes the Apoptosis of Cardiac Muscle Cells in Myocardial Ischemia-Reperfusion Based on Smart Healthcare.

With the development of information technology, the concept of smart healthcare has gradually come to the fore. Smart healthcare uses a new generation of information technologies, such as the Internet of Things (loT), big data, cloud computing, and artificial intelligence, to transform the traditional medical system in an all-around way, making healthcare more efficient, more convenient, and more personalized. miRNAs can regulate the proliferation, differentiation, and apoptosis of human cells. Relevant studies have also shown that miRNAs may play a key role in the occurrence and development of myocardial ischemia-reperfusion injury (MIRI). This study aims to explore the effects of miR-489 in MIRI. In this study, miR-489 expression in a myocardial ischemia-reperfusion animal model and H9C2 cells induced by H/R was detected by qRT-PCR. The release of lactate dehydrogenase (LDH) and the activity of creatine kinase (CK) was detected after miR-489 knockdown in H9C2 cells induced by H/R. The apoptosis of H9C2 cells and animal models were determined by ELISA. The relationship between miR-489 and SPIN1 was verified by a double fluorescence reporter enzyme assay. The expression of the PI3K/AKT pathway-related proteins was detected by Western blot. Experimental results showed that miR-489 was highly expressed in cardiac muscle cells of the animal model and in H9C2 cells induced by H/R of the myocardial infarction group, which was positively associated with the apoptosis of cardiac muscle cells with ischemia-reperfusion. miR-489 knockdown can reduce the apoptosis of cardiac muscle cells caused by ischemia-reperfusion. In downstream targeting studies, it was found that miR-489 promotes the apoptosis of cardiac muscle cells after ischemia-reperfusion by targeting the inhibition of the SPIN1-mediated PI3K/AKT pathway. In conclusion, high expression of miR-489 is associated with increased apoptosis of cardiac muscle cells after ischemia-reperfusion, which can promote the apoptosis after ischemia-reperfusion by targeting the inhibition of the SPIN1-mediated PI3K/AKT pathway. Therefore, miR-489 can be one of the potential therapeutic targets for reducing the apoptosis of cardiac muscle cells after ischemia-reperfusion.

Polymorphisms of RIG-I-like receptor influence HBV clearance in Chinese Han population.

Retinoic acid-inducible gene I-like receptors (RLRs) play an essential role in human innate immune, which may influence the spontaneous clearance of hepatitis B virus (HBV) infection. We aimed to investigate whether the SNPs in RLR family were associated with HBV spontaneous clearance. The current study included 82 participants with spontaneous clearance, 601 asymptomatic hepatitis B surface antigen (HBsAg) carriers, and 168 participants with chronic hepatitis B (CHB). Six SNPs (DDX58 rs3824456, rs3205166, DHX58 rs2074160, rs2074158, IFIH1 rs2111485, rs3747517) were genotyped to explore their association with HBV spontaneous clearance. Patients carrying the mutant allele C at rs3824456 or A at rs2074160 were more likely to achieve spontaneous clearance compared with asymptomatic HBsAg carriers (additive model: odds ratio [OR] = 0.69, 95% confidence interval [CI] = 0.49-0.97; dominant model: OR = 0.54, 95% CI = 0.31-0.95, respectively). In addition, patients carrying the mutant allele G at rs2111485 were more likely to achieve spontaneous clearance compared with CHB (dominant model: OR = 0.47, 95% CI = 0.25-0.87). The mutations were protective factors for HBV spontaneous clearance. These results suggest the DDX58 rs3824456, DHX58 s2074160, IFIH1 rs2111485 were associated with spontaneous clearance of HBV, which may be predictive markers in the Chinese Han population of HBV.

The Coordination and Luminescence of the Eu(III) Complexes with the Polymers (PMMA, PVP).

The rare earth complexes and the polymers can be made into composite nanofibers through electrospinning. The fluorescence intensity of these fiber composites is much higher than that of the rare earth complexes. By changing the mixed proportion of polymethyl methacrylate (PMMA) and complexes, nanofiber materials were prepared. Then, by measuring their fluorescence intensity, it is found that the carbonyl bond of PMMA may have coordinated with the rare earth ions and enhanced the luminescence intensity of them. Then, a series of experiments were designed to study their coordination and luminescence mechanism. The coordination mechanism of the polymers with carbonyl groups and the rare earth complexes was explained by Eu(TFT)3(TPPO), Eu(TFT)3(TPPO)2, Eu(PFP)3(TPPO), Eu(PFP)3(TPPO)2, and polyvinyl pyrrolidone (PVP) dissolved in chloroform solution, where TFT means 2-(2,2,2-trifluoroethyl)-1-tetralone, PFP means 2-(2,2,3,3,3-Pentafluoropro-panoyl)-3,4-dihydronaphthalen-1(2H)-one and TPPO means phosphine oxide. The coordination of PVP and the rare earth complexes in solution was studied, and it was found that the fluorine atoms of the ligand had a significant impact on the aggregation-induced effect of the composites. The electron transitioned in the polymers and the complexes were enhanced greatly by the coordination. The colors of emission light could be adjusted by the coordination of the polymers and the rare earth complexes.

MicroRNA-34a protects myocardial cells against ischemia-reperfusion injury through inhibiting autophagy via regulating TNFα expression.

BACKGROUND: ischemia-reperfusion (I/R) is a consequence of restored blood supply after myocardial infarction. Myocardial I/R injury can be alleviated by reducing autophagy in heart tissue. MicroRNA-34a (miR-34a) has been shown to regulate autophagy in a renal model of I/R, but it is not known whether it can protect cardiac tissues from I/R injury. This study investigated how miR-34a protects myocardial cells from I/R injury by inhibiting autophagy via regulation of tumor necrosis factor α (TNFα). METHODS: we constructed an I/R model in vivo using Langendorff perfusion, and we constructed an in vivo model by treating neonatal rat cardiomyocytes (NRCMs) with hypoxia-reoxygenation (H/R method). Transfected adenoviral-overexpressed miR-34a mimics and controlled NRCMs after H/R. We analyzed cell viability using the MTT assay and a cell counting kit-8 (CCK-8) assay. Changes in the rate of apoptosis were detected by flow cytometry. We investigated the effect mechanisms of miR-34a with Western blot and luciferase assays. RESULTS: miR-34a expression decreased after in vivo reperfusion of the myocardial cells and heart tissues of neonatal rats. MiR-34a reduced apoptosis of the NRCMs and autophagy levels, simultaneously, after H/R injury. Further, miR-34a decreased the expression of Lc3-II and p62, indicating that miR-34a reduces myocardial I/R injury by decreasing TNFα expression. CONCLUSION: miR-34a can inhibit autophagy levels after I/R by targeting TNFα, thereby reducing myocardial injury.

Update of incidence and antimicrobial susceptibility trends of Escherichia coli and Klebsiella pneumoniae isolates from Chinese intra-abdominal infection patients.

BACKGROUND: To evaluate in vitro susceptibilities of aerobic and facultative Gram-negative bacterial (GNB) isolates from intra-abdominal infections (IAIs) to 12 selected antimicrobials in Chinese hospitals from 2012 to 2014. METHODS: Hospital acquired (HA) and community acquired (CA) IAIs were collected from 21 centers in 16 Chinese cities. Extended spectrum beta-lactamase (ESBL) status and antimicrobial susceptibilities were determined at a central laboratory using CLSI broth microdilution and interpretive standards. RESULTS: From all isolated strains the Enterobacteriaceae (81.1%) Escherichia coli accounted for 45.4% and Klebsiella pneumoniae for 20.1%, followed by Enterobacter cloacae (5.2%), Proteus mirabilis (2.1%), Citrobacter freundii (1.8%), Enterobacter aerogenes (1.8%), Klebsiella oxytoca (1.4%), Morganella morganii (1.2%), Serratia marcescens (0.7%), Citrobacter koseri (0.3%), Proteus vulgaris (0.3%) and others (1.0%). Non- Enterobacteriaceae (18.9%) included Pseudomonas aeruginosa (9.8%), Acinetobacter baumannii (6.7%), Stenotrophomonas maltophilia (0.9%), Aeromonas hydrophila (0.4%) and others (1.1%). ESBL-screen positive Escherichia coli isolates (ESBL+) showed a decreasing trend from 67.5% in 2012 to 58.9% in 2014 of all Escherichia coli isolates and the percentage of ESBL+ Klebsiella pneumoniae isolates also decreased from 2012 through 2014 (40.4% to 26.6%), which was due to reduced percentages of ESBL+ isolates in HA IAIs for both bacteria. The overall susceptibilities of all 5160 IAI isolates were 87.53% to amikacin (AMK), 78.12% to piperacillin-tazobactam (TZP) 81.41% to imipenem (IMP) and 73.12% to ertapenem (ETP). The susceptibility of ESBL-screen positive Escherichia coli strains was 96.77%-98.8% to IPM, 91.26%-93.16% to ETP, 89.48%-92.75% to AMK and 84.86%-89.34% to TZP, while ESBL-screen positive Klebsiella pneumoniae strains were 70.56%-80.15% susceptible to ETP, 80.0%-87.5% to IPM, 83.82%-87.06% to AMK and 63.53%-68.38% to TZP within the three year study. Susceptibilities to all cephalosporins and fluoroquinolones were less than 50% beside 66.5% and 56.07% to cefoxitin (FOX) for ESBL+ Escherichia coli and Klebsiella pneumoniae strains respectively. CONCLUSIONS: The total ESBL+ rates decreased in Escherichia coli and Klebsiella pneumoniae IAI isolates due to fewer prevalence in HA infections. IPM, ETP and AMK were the most effective antimicrobials against ESBL+ Escherichia coli and Klebsiella pneumoniae IAI isolates in 2012-2014 and a change of fluoroquinolone regimens for Chinese IAIs is recommended.

Antimicrobial susceptibilities of aerobic and facultative gram-negative bacilli isolated from Chinese patients with urinary tract infections between 2010 and 2014.

BACKGROUND: The objective of this study was to investigate the distribution and susceptibility of aerobic and facultative Gram-negative bacilli isolated from Chinese patients with UTIs collected within 48 h (community acquired, CA) or after 48 h (hospital acquired, HA) of hospital admission. METHODS: From 2010 to 2014, the minimum inhibitory concentrations (MICs) of 12 antibiotics for 4,332 aerobic and facultative Gram-negative bacilli, sampled in 21 hospitals in 16 cities, were determined by the broth microdilution method. RESULTS: Enterobacteriaceae composed 88.5% of the total isolates, with Escherichia coli (E. coli) (63.2%) the most commonly isolated species, followed by Klebsiella pneumoniae (K. pneumoniae) (12.2%). Non-Enterobacteriaceae accounted for only 11.5% of all isolates and included mainly Pseudomonas aeruginosa (P. aeruginosa) (6.9%) and Acinetobacter baumannii (A. baumannii) (3.3%). Among the antimicrobial agents tested, the susceptibility rates of E.coli to the two carbapenems, ertapenem and imipenem as well as amikacin and piperacillin-tazobactam ranged from 92.5 to 98.7%. Against K. pneumonia, the most potent antibiotics were imipenem (92.6% susceptibility), amikacin (89.2% susceptibility) and ertapenem (87.9% susceptibility). Although non-Enterobacteriaceae did not show high susceptibilities to the 12 common antibiotics, amikacin exhibited the highest in vitro activity against P. aeruginosa over the 5-year study period, followed by piperacillin-tazobactam, imipenem, ceftazidime, cefepime, ciprofloxacin, and levofloxacin. The Extended Spectrum Beta-Lactamase (ESBL) rates decreased slowly during the 5 years in E. coli from 68.6% in 2010 to 59.1% in 2014, in K. pneumoniae from 59.7 to 49.2%, and in Proteus mirabilis (P. mirabilis) from 40.0 to 26.1%. However, the ESBL rates were different in 5 regions of China (Northeast, North, East, South and Middle-China). CONCLUSION: E. coli and K. pneumonia were the major pathogens causing UTIs and carbapenems and amikacin retained the highest susceptibility rates over the 5-year study period, indicating that they are good drug choices for empirical therapies, particularly of CA UTIs in China.

Molecular characteristics of extended-spectrum ß-lactamase-producing Escherichia coli and Klebsiella pneumoniae causing intra-abdominal infections from 9 tertiary hospitals in China.

BACKGROUND: Recently, the emergence of multidrug-resistant organisms such as extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae has raised considerable concern regarding the appropriate treatment of intra-abdominal infections (IAIs). In this study, we investigated the molecular characteristics of ESBL among clinical isolates of Escherichia coli and Klebsiella pneumoniae causing IAIs and their pattern of antimicrobial resistance, which can provide useful information about the epidemiology and risk factors associated with these infections. MATERIALS AND METHODS: One hundred sixty-seven E.coli and 47 K. pneumoniae ESBL-producing strains causing IAIs were collected from 9 hospitals in China, during 2012 and 2013. The antimicrobial susceptibility profile of these strains was determined. Polymerase chain reaction and sequencing were performed to identify genes for ß-lactamase (blaTEM, blaSHV, blaOXA-1-like, and blaCTX-M). The isolates were also analyzed by pulsed-field gel electrophoresis (PFGE). RESULTS: In 167 ESBL-producing E. coli strains, 104 strains (62.3%) were positive for CTX-M, and 9 strains (5.39%) were positive for SHV. Among the 47 K. pneumoniae strains, 35 strains (74.5%) were positive for SHV-2a, 12 strains (25.5%) were positive for CTX-M. No TEM-type and OXA-1-like strain was detected among all the ESBL-producing strains. Regarding the CTX-M-positive E. coli and K. pneumoniae strains, CTX-M-15 was the most common genotype in E. coli and K. pneumoniae strains, accounting for 28.7% and 17.0%, respectively, followed by CTX-M-55 accounting for 16.2% and 2.13%, respectively; the remaining genotypes included CTX-M-123 and CTX-M-82. PFGE showed that E.coli and K. pneumoniae ESBL-producing strains causing IAIs were diverse and that emerging resistance may not be due to the dissemination of national clones. CONCLUSION: The present study revealed that in ESBL-producing strains causing IAIs in China, the most common genotype for E.coli was CTX-M-15 and for K. pneumoniae was SHV-2a. However, there was a wide diversity of strains causing IAIs among the ESBL-producing E. coli and K. pneumoniae.

Antimicrobial Susceptibilities of Aerobic and Facultative Gram-Negative Bacilli from Intra-abdominal Infections in Patients from Seven Regions in China in 2012 and 2013.

To evaluate the antimicrobial susceptibility of Gram-negative bacilli that caused hospital-acquired and community-acquired intra-abdominal infections (IAIs) in China between 2012 and 2013, we determined the susceptibilities to 12 antimicrobials and the extended-spectrum ß-lactamase (ESBL) statuses of 3,540 IAI isolates from seven geographic areas in China in a central laboratory using CLSI broth microdilution and interpretive standards. Most infections were caused by Escherichia coli (46.3%) and Klebsiella pneumoniae (19.7%). Rates of ESBL-producing E. coli (P = 0.031), K. pneumoniae (P = 0.017), and Proteus mirabilis (P = 0.004) were higher in hospital-acquired IAIs than in community-acquired IAIs. Susceptibilities of enterobacteriaceae to ertapenem, amikacin, piperacillin-tazobactam, and imipenem were 71.3% to 100%, 81.3% to 100%, 64.7% to 100%, and 83.1% to 100%, respectively, but imipenem was ineffective against P. mirabilis (<20%). Although most ESBL-positive hospital-acquired isolates were resistant to third- and fourth-generation cephalosporins, the majority were susceptible to cefoxitin (47.9% to 83.9%). Susceptibilities of ESBL-positive isolates to ampicillin-sulbactam (<10%) were low, whereas susceptibilities to ciprofloxacin (0% to 54.6%) and levofloxacin (0% to 63.6%) varied substantially. The prevalences of cephalosporin-susceptible E. coli and K. pneumoniae were higher in the northeastern and southern regions than in the central and eastern regions, reflecting the ESBL-positive rates in these areas, and were lowest in the Jiangsu-Zhejiang (Jiang-Zhe) area where the rates of carbapenem resistance were also highest. Ertapenem, amikacin, piperacillin-tazobactam, and imipenem are the most efficacious antibiotics for treating IAIs in China, especially those caused by E. coli or K. pneumoniae. Resistance to cephalosporins and carbapenems is more common in the Jiang-Zhe area than in other regions in China.

On-chip microwave signal generation based on a silicon microring modulator.

A photonic-assisted microwave signal generator based on a silicon microring modulator is demonstrated. The microring cavity incorporates an embedded PN junction that enables a microwave signal to modulate the lightwave circling inside. The DC component of the modulated light is trapped in the cavity, while the high-order sideband components are able to exit the cavity and then generate microwave signals at new frequencies in a photodetector. In our proof-of-concept experiment, a 10 GHz microwave signal is converted to a 20 GHz signal in the optical domain with an electrical harmonic suppression ratio of 22 dB. An analytic model is also established to explain the operation mechanism, which agrees well with the measured data.

In vitro activity of flomoxef and comparators against Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis producing extended-spectrum ß-lactamases in China.

The objective of this study was to better understand the in vitro activity of flomoxef against clinical extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae. A total of 401 ESBL-producing isolates, including 196 Escherichia coli, 124 Klebsiella pneumoniae and 81 Proteus mirabilis, were collected consecutively from 21 hospitals in China in 2013. Minimum inhibitory concentrations (MICs) were determined by broth microdilution methods. Phenotypic identification of ESBL production was detected as recommended by the Clinical and Laboratory Standards Institute (CLSI). ESBL genes were detected by PCR and sequencing. Flomoxef, doripenem, meropenem, ertapenem, cefmetazole and piperacillin/tazobactam exhibited good activity against ESBL-producing isolates, with susceptibility rates >90%. Tigecycline showed good activity against E. coli and K. pneumoniae (100% and 97.6%, respectively). Cefotaxime and cefepime showed very low activities against ESBL-producing isolates, with susceptibility rates of 0-0.8% and 1.0-13.6%, respectively. blaCTX-M were the major ESBL genes, with occurrence in 99.5% of E. coli, 91.1% of K. pneumoniae and 97.5% of P. mirabilis. blaCTX-M-14 was the predominant ESBL gene, detected in 46.9% (188/401) of the isolates, followed by blaCTX-M-15 (21.4%), blaCTX-M-55 (17.2%), blaCTX-M-65 (12.7%) and blaCTX-M-3 (6.7%). Flomoxef exhibited excellent activity against the different CTX-M-type ESBL-producing isolates, with MIC50 and MIC90 values of 0.064-0.125µg/mL and 0.25-0.5µg/mL, respectively. Against the isolates solely producing CTX-M-14, -15, -55, -3 or -65, flomoxef showed susceptibility rates of 98.6%, 98.0%, 98.1%, 100.0% and 97.4%, respectively. In conclusion, flomoxef showed good activity against ESBL-producing Enterobacteriaceae and may be a choice to treat infections caused by these isolates in China.