Concentration-resistance relationship and PK/PD evaluation of danofloxacin against emergence of resistant Pasteurella multocida in an in vitro dynamic model.

AIMS: This study aimed to assess the pharmacokinetic/pharmacodynamic (PK/PD) targets of danofloxacin to minimize the risk of selecting resistant Pasteurella multocida mutants and to identify the mechanisms underlying their resistance in an in vitro dynamic model, attaining the optimum dosing regimen of danofloxacin to improve its clinical efficacy based on the mutant selection window (MSW) hypothesis. METHODS AND RESULTS: Danofloxacin at seven dosing regimens and 5 days of treatment were simulated to quantify the bactericidal kinetics and enrichment of resistant mutants upon continuous antibiotic exposure. The magnitudes of PK/PD targets associated with different efficacies were determined in the model. The 24 h area under the concentration-time curve (AUC) to minimum inhibitory concentration (MIC) ratios (AUC24h/MIC) of danofloxacin associated with bacteriostatic, bactericidal and eradication effects against P. multocida were 34, 52, and 64 h. This translates to average danofloxacin concentrations (Cav) over 24 h being 1.42, 2.17, and 2.67 times the MIC, respectively. An AUC/MIC-dependent antibacterial efficacy and AUC/mutant prevention concentration (MPC)-dependent enrichment of P. multocida mutants in which maximum losses in danofloxacin susceptibility occurred at a simulated AUC24h/MIC ratio of 72 h (i.e. Cav of three times the MIC). The overexpression of efflux pumps (acrAB-tolC) and their regulatory genes (marA, soxS, and ramA) was associated with reduced susceptibility in danofloxacin-exposed P. multocida. The AUC24h/MPC ratio of 19 h (i.e. Cav of 0.8 times the MPC) was determined to be the minimum mutant prevention target value for the selection of resistant P. multocida mutants. CONCLUSIONS: The emergence of P. multocida resistance to danofloxacin exhibited a concentration-dependent pattern and was consistent with the MSW hypothesis. The current clinical dosing regimen of danofloxacin (2.5 mg kg-1) may have a risk of treatment failure due to inducible fluoroquinolone resistance.

Broadband generation of a multi-polarization multi-beam using a receiving-transmitting metasurface.

Generating multiple beams in distinct polarization states is promising in multi-mode wireless communication but still remains challenging in metasurface design. Here, we theoretically and experimentally demonstrate a concept of broadband receiving-transmitting metasurface and its application to the generation of multi-polarization multi-beam. By employing U-slot patch, an efficient receiving-transmitting element with full phase coverage is designed within a wide bandwidth. Based on this architecture, a methodology is proposed to generate dual spin-decoupled beams and then developed into the strategy of generating multiple beams at different linear polarizations. To verify our strategy, two lens antennas, respectively radiating dual-spin dual-beam and quad-polarization quad-beam, are devised. With multi-polarization multi-beam radiated, the two lens antennas are both with whole aperture efficiency above 40% within the bandwidth of 10.6-12.3 GHz (14.8%), firmly validating our strategy and design.

Analysis of Medication Rules of Traditional Chinese Medicine for Malaria Treatment Based on Data Mining.

Objective To analyze the medication rules of traditional Chinese medicine (TCM) for malaria treatment.Methods Statistical analysis was conducted on the basic attributes of TCM drugs with regard to property, therapeutic methods, flavor, and meridian tropism. A complex network of TCM drug associations was constructed. Cluster analysis was applied to obtain the core drugs for malaria treatment. The Apriori algorithm was applied to analyze the association rules of these core drugs.Results A total of 357 herbs were used 3,194 times in 461 prescriptions for malaria treatment. Radix Glycyrrhizae (), Rhizoma Pinelliae (), Radix Bupleuri (), and Radix Dichroae () were the frequently used herbs through supplementing, exterior-releasing, heat-clearing, qi-rectifying, and damp-resolving therapeutic methods. Such herbs had warm, natural, and cold herbal properties; pungent, bitter, and sweet flavors; and spleen, lung, and stomach meridian tropisms. Cluster analysis showed 61 core drugs, including Radix Glycyrrhizae, Rhizoma Pinelliae, Radix Bupleuri, and Radix Scutellariae (). Apriori association rule analysis yielded 12 binomial rules (herb pairs) and 6 trinomial rules (herb combinations). Radix Bupleuri plus Radix Scutellariae was the core herbal pair for treating malaria. This pair could be combined with Rhizoma Atractylodis Macrocephalae () for treating warm or cold malaria, combined with Pericarpium Citri Reticulatae () or Radix Dichroae () for treating miasmic malaria, or combined with turtle shells () for treating malaria with splenomegaly.Conclusions TCM can be used to classify and treat malaria in accordance with the different stages of development. As the core herbal pair, Radix Bupleuri and Radix Scutellariae can be combined with other drugs to treat malaria with different syndrome types.

Quad-channel independent wavefront encoding with dual-band multitasking metasurface.

Achieving multiple electromagnetic (EM) functionalities on a shared aperture in dual frequency bands is crucial for many applications; however, existing dual-band metasurfaces are affected by limited channels or narrow bandwidths. Herein, we propose a reflective coding metasurface that empowers four independent EM functionalities in quad-polarization channels in two wide frequency bands. By integrating quasi-I-shaped and cross-shaped metastructures, the meta-atom can feature independent phase modulation for two orthogonally linear and two decoupled circular polarizations at low and high frequencies, respectively. To validate the proposed metasurface, a multifunctional metadevice is designed that integrates beam deflection, diffuse scattering, and vortex beam generation. Both experimental and simulation results indicate distinct wavefront tailoring in each channel. The proposed multi-functional metasurface with low cross-talk and independent phase modulation depending on frequencies and polarizations may unlock the metasurfaces' potentials for complete wavefront control in EM function integration, multiple channel communication, polarization optics, etc.

Multi-functional coding metasurface for dual-band independent electromagnetic wave control.

Multi-functional metasurfaces have exhibited powerful abilities of manipulating electromagnetic (EM) wave in predetermined manners, largely improving their information capacities. However, most works are implemented with EM functions controlled by one of the intrinsic properties of EM wave, such as polarization, frequency, etc. Herein, we propose a coding scheme to design a broadband and high-efficient multi-functional metasurface independently controlled by both frequency and polarization. To achieve this goal, we design anisotropic coding particles to realize independent phase functions and polarization-selectivity in the microwave region. Meta-atoms are finally optimized to exhibit 2-bit phase responses insensitive to incident polarization in the X-band while showing a 1-bit phase shift sensitive to incident polarization in the Ku-band. As a proof of concept, a metasurface is configured as an isotropic lens in the X-band, whereas the metasurface is designed as an anisotropic beam deflector in the Ku-band with or without polarization-conversion functionality dependent on the input polarization. The measured results, which agree well with the simulated ones, show excellent performances in the designed dual bands. Such a multi-functional coding metasurface may provide a flexible and robust approach to manipulate EM wave of multiple frequencies, as well as to integrate diverse functionalities into a single flat device.

Clinical Features of Brain Metastases in Small Cell Lung Cancer: an Implication for Hippocampal Sparing Whole Brain Radiation Therapy.

PURPOSE: To assess the clinical features and distribution of brain metastases (BMs) of small cell lung cancer (SCLC) in the hippocampal and perihippocampal region, with the purpose of exploring the viability of hippocampal-sparing whole-brain radiation therapy (HS-WBRT) on reducing neurocognitive deficits. METHODS: This was a retrospective analysis of the clinical characteristics and patterns of BMs in patients with SCLC. Associations between the clinical characteristics and hippocampal metastases (HMs)/perihippocampal metastases (PHMs) were evaluated in univariate and multivariate regression analyses. RESULTS: A total of 1594 brain metastatic lesions were identified in 180 patients. Thirty-two (17.8%) patients were diagnosed with BMs at the time of primary SCLC diagnosis. The median interval between diagnosis of primary SCLC and BMs was 9.3 months. There were 9 (5.0%) and 22 (12.2%) patients with HMs and PHMs (patients with BMs located in or within 5 mm around the hippocampus), respectively. In the univariate and multivariate analysis, the number of BMs was the risk factor for HMs and PHMs. Patients with BMs≥5 had significantly higher risk of HMs (odds ratio [OR] 7.892, 95% confidence interval [CI] 1.469-42.404, P=.016), and patients with BMs≥7 had significantly higher risk of PHMs (OR 5.162, 95% CI 2.017-13.213, P=.001). Patients with extracranial metastases are also associated with HMs. CONCLUSIONS: Our results indicate that patients with nonoligometastatic disease are significantly associated with HMs and PHMs. The incidence of PHMs may be acceptably low enough to perform HS-WBRT for SCLC. Our findings provide valuable clinical data to assess the benefit of HS-WBRT in SCLC patients with BMs.

[Neuroendoscopic treatment for 372 cases of intracranial lesions].

OBJECTIVE: To explore the application of neuroendoscopic treatment for intracranial lesions. METHODS: The clinic data of 372 patients with intracranial lesions, who underwent neuroendoscopic treatment at our department from May 1998 to May 2010, were reviewed retrospectively. Representative endoscopic treatments included endoscopic third ventriculostomy (ETV) (n = 198), ETV & endoscopic biopsy (n = 69), neuroendoscopic ostomy for septum pellucidum fenestration (n = 55) (for septum pellucidum cysts, n = 37) and endoscopic cystoventriculostomy for ventricular cysts (n = 50). Their surgical indications and clinical outcomes were summarized for analysis. RESULTS: ETV was performed successfully in 369 cases. Among them, 2 failed cases underwent other operations and endoscopic biopsy failed in 1 case. Within a short post-operative period, the symptoms were resolved in 347 cases (93.3%), showed no improvement in 23 cases (6.2%) and 2 died (0.5%). At Month 6 post-operation, a failure of ETV was detected in 22 cases (9.5%), a failure of neuroendoscopic ostomy for septum pellucidum cysts in 23 (69.7%) and for ventricular cysts in 12 cases (26.7%). CONCLUSION: ETV is effective in the treatment of obstructive hydrocephalus, but its indication should be strictly controlled for children. Effective rate of neuroendoscopic treatment for intracranial septum pellucidum cysts remains unsatisfactory so that its operative indication should be strictly controlled.

[Common failure reasons and improvement ways in treatment of gallstones by choledochoscope in operation].

OBJECTIVE: To analyze common problems, failing causes and improvement ways for curing gallstones by choledochoscope in operation. METHOD: To analyze a case group of 762 individual patients who had undergone choledochoscope operations in the period of Jan, 1995 approximately Sep, 2005. RESULTS: 136 cases are found with residual stones in the bile duct after the operations. Residual stone rate amounts to 17.8%. 55 patients are known that bile duct stones could not be remove completely during operations. 81 patients are proved that stones still remain in their bile ducts by T-tube cholangiography and choledochoscope after operations. Among them, 29 patients complicate with narrow in intrahepatic bile ducts and debouch of bile ducts, 39 patients complicate with stones of intrahepatic bile and variation of bile duct, 13 patients complicate with stones and narrow at the inferior segment of choledochus. CONCLUSIONS: It is important to pay attention for bile duct variation and debouch of affection bile duct or inferior segment of choledochus stenosis. B-ultrasound is useful to reduce residual stones in operations. The surgeon should check different lengths of the duct methodically, and use the endoscope to explore the bile duct in order not to omit any stones.

Correlation of obesity with C-reactive protein, leptin and insulin sensitive index in children / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the correlation between obesity and hypersensitive C-reactive protein (hsCRP), leptin, and insulin sensitive index (ISI) in children.</p><p><b>METHODS</b>The subjects included 69 obese volunteers and 30 age and gender-matched normal volunteers who were recruited from 13702 children aged 2 to 18 years in Xiangtan City by sampling survey. The body mass index (BMI), hsCRP, leptin, fasting plasma glucose (FPG), and fasting insulin (INS) were tested, and then the ISI was calculated. The results between the obese and normal children were compared. The correlation between the parameters was evaluated.</p><p><b>RESULTS</b>The values of hsCRP, leptin and INS in obese children were significantly higher than those in the normal controls (P < 0.01), but the ISI in obese children was significantly lower than that in normal controls (P < 0.01). The BMI was significantly positively correlated with the values of hsCRP, leptin and INS (r=0.225, P < 0.05; r=0.776, P < 0.01; r=0.568, P < 0.01), but was significantly negatively correlated with the ISI (r=-0.889, P < 0.01). There was a positive correlation between the value of hsCRP and the values of FPG and INS (r=0.429, P < 0.01; r=0.206, P < 0.05), and there was a negative correlation between the value of hsCRP and the ISI (r=-0.889, P < 0.01). The value of leptin significantly positively correlated with the values of INS and BMI, and significantly negatively correlated with the ISI.</p><p><b>CONCLUSIONS</b>Insulin resistance and leptin resistance exist in obese children. The inflammatory factors such as CRP and leptin may be involved in the pathogenesis of obesity.</p>