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Background: Nemonoxacin, a novel nonfluorinated quinolone, has broad-spectrum antibacterial activity, including activity against antibiotic-resistant strains, and was developed for treating community-acquired pneumonia (CAP). This report provides an integrated safety summary of oral nemonoxacin from two phase II and one phase III clinical studies. Methods: Patients with mild CAP were randomized for treatment with nemonoxacin 500 mg (NEMO-500MG), nemonoxacin 750 mg (NEMO-750MG), or levofloxacin 500 mg (LEVO), orally, once daily, for 7–10 days. Hematological, gastrointestinal, and hepatic disorders; electrocardiography abnormalities; and reported quinolone-associated clinical concerns were included in this analysis. Results: A total of 520, 155, and 320 subjects were assigned to receive NEMO-500MG, NEMO-750MG, and LEVO, respectively. The incidence of adverse events (AEs) was the highest (54.8%) in the NEMO-750MG group (NEMO-500MG, 36.9%; NEMO-750MG, 54.8%; LEVO, 39.7%) and that of drug-related AEs was comparable between the three groups (NEMO-500MG, 22.9%; NEMO-750MG, 31.0%; LEVO, 22.5%). The majority (>80%) of the patients showed mild drug-related AEs and the distribution based on severity was similar between the groups. The most commonly reported drug-related AEs included neutropenia (NEMO-500MG, 2.5%; NEMO-750MG, 8.4%; LEVO, 4.4%), nausea (NEMO-500MG, 2.5%; NEMO-750MG, 7.1%; LEVO, 2.5%), leukopenia (NEMO-500MG, 2.3%; NEMO-750MG, 4.5%; LEVO, 3.1%), and increased alanine aminotransferase level (NEMO-500MG, 4.4%; NEMO-750MG, 0%; LEVO, 2.5%). Conclusion: Nemonoxacin was well tolerated and no clinically significant safety concerns were identified, suggesting that it possesses a desirable safety and tolerability profile similar to that of levofloxacin, and may be a suitable alternative to fluoroquinolones for treating patients with CAP. Keywords: Community-acquired pneumonia, Fluoroquinolone, Levofloxacin, Nemonoxacin, Safety

The aim of this study was to explore the associations and differences in influencing factors between alcoholic liver disease (ALD) coupled with Helicobacter pylori infection and atherosclerosis and to determine whether there is a “double hit phenomenon” in atherosclerosis patients with ALD and H. pylori infections. Included cases (n = 160) were categorized into 4 groups: 41 cases of ALD coupled with H. pylori infections (group A), 35 cases of H. pylori infections without ALD (group B), 37 cases of ALD without H. pylori infections (group C), and 47 normal control cases (group D). CIMT was significantly greater in group A than in groups B and D (P = 0.005 and P = 0.001, respectively). The GLM univariate analysis found that CIMT was significantly greater in group A than in groups B, C and D (P = 0.018, P = 0.001 and P = 0.009, respectively). We found that BMI and ALT, AST and ApoB levels were independent predictors of CIMT (P = 0.000, P = 0.000, P = 0.012 and P = 0.014, respectively). ALD coupled with H. pylori infection may result in significant CIMT thickening, but H. pylori infection without ALD and ALD without H. pylori infection does not, suggesting that a “double hit phenomenon” occurs. Additionally, BMI, and ALT, AST and ApoB levels were independent risk factors for increased CIMT.

the FEM model of unitary body of HEV city bus was established, and the model accuracy was proved by electric measurement. The Sensitivity analysis of stiffness was conducted to determine variables for optimization design basing on special analysis software tools. At last, the plan was formed to reach design target of light weight with least stiffness change and regulated strength of vehicle body.

Nemonoxacin, a novel nonfluorinated quinolone, exhibits potent in vitro and in vivo activities against community-acquired pneumonia (CAP) pathogens, including multidrug-resistant Streptococcus pneumoniae . Patients with mild to moderate CAP ( n = 265) were randomized to receive oral nemonoxacin (750 mg or 500 mg) or levofloxacin (500 mg) once daily for 7 days. Clinical responses were determined at the test-of-cure visit in intent-to-treat (ITT), clinical per protocol (PPc), evaluable-ITT, and evaluable-PPc populations. The clinical cure rates for 750 mg nemonoxacin, 500 mg nemonoxacin, and levofloxacin were 89.9%, 87.0%, and 91.1%, respectively, in the evaluable-ITT population; 91.7%, 87.7%, and 90.3%, respectively, in the evaluable-PPc population; 82.6%, 75.3%, and 80.0%, respectively, in the ITT population; and 83.5%, 78.0%, and 82.3%, respectively, in the PPc population. Noninferiority to levofloxacin was demonstrated in both the 750-mg and 500-mg nemonoxacin groups for the evaluable-ITT and evaluable-PPc populations, and also in the 750 mg nemonoxacin group for the ITT and PPc populations. Overall bacteriological success rates were high for all treatment groups in the evaluable-bacteriological ITT population (90.2% in the 750 mg nemonoxacin group, 84.8% in the 500 mg nemonoxacin group, and 92.0% in the levofloxacin group). All three treatments were well tolerated, and no drug-related serious adverse events were observed. Overall, oral nemonoxacin (both 750 mg and 500 mg) administered for 7 days resulted in high clinical and bacteriological success rates in CAP patients. Further, good tolerability and excellent activity against common causative pathogens were demonstrated. Nemonoxacin (750 mg and 500 mg) once daily is as effective and safe as levofloxacin (500 mg) once daily for the treatment of CAP.

Background/Purpose Patients on prolonged mechanical ventilation in Taiwan are stepped down to a respiratory care ward (RCW) for further respiratory care. Only a few patients in the RCW can ultimately be weaned and discharged. In this study, we tried to determine factors that predict mortality and readmission of these patients in the post-discharge period. Methods Between May 1, 2004 and October 31, 2006, clinical data were retrospectively analyzed for eligible patients in a RCW. Patients who were successfully weaned from mechanical ventilation were enrolled in this study. Results A total of 243 patients were eligible for evaluation, and 67 patients were successfully weaned and discharged. By Kaplan-Meier curve, 36 (67.1%) patients were readmitted within 3 months after discharge, and among these, 23 (63.9%) had mechanical ventilation reinstituted at the time of first readmission. The most common cause of readmission was airway infection (80.5%). Overall mortality and readmission rates at 1 year after weaned discharge were 32.9% and 88.2%, respectively. By multivariate analysis, patients with neurologic causes of ventilator dependency were less likely to be readmitted (hazard ratio = 0.36; p =0.034), and neoplastic diseases (hazard ratio = 4.66; p =0.031) were independently associated with mortality. Conclusion Underlying comorbidities and causes of ventilator dependency are important predictors of mortality and readmission among patients after weaned discharge from a RCW.

Purpose This study aimed to evaluate the impact of previous antibiotic exposure and the influence of time interval since exposure on the evolution of antibiotic-resistant infections. Methods We retrospectively analyzed 167 mechanically ventilated patients with nosocomial infections over a 3-year period, with focus on infections in the bloodstream, urinary tract, lower respiratory tract, and surgical sites. Results Of 167 patients, 62% were confirmed as antibiotic resistant. The most common isolated pathogen was extended-spectrum β-lactamase Enterobacteriaceae (43.9%), followed by methicillin-resistant Staphylococcus aureus (22.8%), and carbapenem-resistant Acinetobacter baumannii (17.5%). Multivariate analysis revealed that the association between resistance and the time interval increased within 10 days (odds ratio [OR], 2.45; P = .133) and peaked at 11 to 20 days (OR, 7.17; P = .012). The data were categorized into 2 groups: when the time interval was more than 20 days, there was a 23.9% reduction in resistance rate compared with when the time interval was 20 days or less (OR, 0.36; P = .002). Conclusions Although antibiotic exposure increased resistance rate in nosocomial infections, this association decreased as time interval increased. Antibiotic stewardship should consider the significance of time interval while investigating the evolution of subsequent antibiotic-resistant infections.

Epidemiological evidence has shown two polymorphisms (namely RS#1800468G>A and RS#1800471G>C) of transforming growth factor-beta 1 (TGF-β1) gene may be involved in the cancer development. However, their role in the carcinogenic process of esophageal squamous cell carcinoma (ESCC) has been less well elaborated. We conducted a hospital-based case-control study including 391 ESCC cases and 508 controls without any evidence of tumors to evaluate the association between these two polymorphisms and ESCC risk and prognosis for Zhuangese population by means of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and amplification refractory mutation system (ARMS)-PCR techniques. We found that individuals with the genotypes with RS#1800471 C allele (namely RS#1800471-GC or -CC) had an increased risk of ESCC than those without above genotypes (namely RS#1800471-GG, adjusted odds ratio 3.26 and 5.65, respectively). Further stratification analysis showed that this polymorphism was correlated with tumor histological grades and TNM (tumor, node, and metastasis) stage, and modified the serum levels of TGF-β1. Additionally, RS#1800471 polymorphism affected ESCC prognosis (hazard ratio, 3.40), especially under high serum levels of TGF-β1 conditions. However, RS#1800468 polymorphism was not significantly related to ESCC risk. These findings indicated that TGF-β1 RS#1800471G>C polymorphism may be a genetic modifier for developing ESCC in Zhuangese population.

With the aim for the resistance mechanism of tobacco to Bemisia tabaci, we determined the chlorophyll content of tobacco leaves, the chemical components and amino acid content in fresh or cured tobacco leaves, and analyzed the correlations between resistance of tobacco to Bemisia tabaci and chemical components of tobacco leaves. Results show that significantly negative correlation occurs between the chlorophyll content in middle tobacco leaves and the population amount of Bemisia tabaci. The ratio of K 2 O to Cl, sugar to nicotine, nitrogen to nicotine, and the contents of reducing sugar, nicotine, protein in fresh leaves are correlated with the resistance of tobacco variety to Bemisia tabaci, yet with no significant level. Involving the chemical components of cured tobacco leaves, nicotine demonstrates the most evident and negative correlation to the amount of Bemisia tabaci, while the ratio of nitrogen to nicotine, the positive. The total amount of amino acid is significantly positive correlated to the amount of Bemisia tabaci. Six amino acids have greater effects on the resistance of tobacco variety, including serine, arginine, threonine, glutamic acid, leucine, lysine, with the correlation coefficient reaching significant level. We conclude that the contents of chlorophyll, nicotine, six amino acids, and the ratio of nitrogen to nicotine have more considerable effects on the resistance of tobacco variety to Bemisia tabaci.

Esophageal squamous cell carcinoma (ESCC) is multifactorial, and the genetic background may be a crucial etiologic factor. Interleukin-18 (IL-18) is a multifunctional cytokine that induces interferon (IFN)-gamma secretion and plays an important role in antitumor immunity. Variations in the DNA sequence in the IL-18 gene promoter may lead to altered IL-18 production and/or activity, and so this can modulate an individual's susceptibility to ESCC. To test this hypothesis, we investigated the relationship of IL-18 gene promoter -137 G/C and -607 C/A polymorphisms and their haplotypes with the risk of ESCC in a Chinese population.Two hundred and thirty five patients with ESCC and 250 age- and sex-matched controls, using sequence specific primers-polymerase chain reaction (PCR-SSP).Two polymorphisms, -137 G/C and -607 C/A were in strong linkage disequilibrium (LD). There were significantly differences in the genotype and allele distribution of -137 G/C polymorphism of the IL-18 gene among cases and controls. The -137 GC and CC genotypes were associated with a significantly increased risk of ESCC as compared with the -137 GG genotypes (OR = 1.91, 95% CI, 1.29-2.82, p = 0.001 and OR = 2.95, 95% CI, 1.23-7.04, p = 0.012, respectively). Consistent with the results of the genotyping analyses, the -137 C/ -607 A haplotype was associated with a significantly increased risk of ESCC as compared with the -137G/-607 C haplotype (OR = 1.61; 95% CI, 1.16-2.23; p = 0.004).This study shows for the first time an association between IL-18 gene promoter -137 G/C polymorphism may contribute represent a genetic risk factor for ESCC in a Chinese population.

Inflammation has recently proven to be associated with the pathogenesis of atherosclerosis and inflammatory genes are good candidates for the risk of developing atherosclerosis. The early phase of atherosclerosis involves the recruitment of inflammatory cells from the circulation and their transendothelial migration. This process is mainly mediated by cellular adhesion molecules. The adhesion molecule P-selectin may play a role in the pathogenesis of atherosclerosis. Polymorphism of P-selectin gene, which may affect the production level of the adhesion molecule, has been associated with a number of atherosclerotic disease. To test this hypothesis, we investigated the relationship of P-selectin gene polymorphisms and ischemic stroke in a Chinese population. We analyzed single nucleotide polymorphisms of P-selectin gene −2,123 G/C, −1,969 G/A, −1,817 T/C and Thr715Pro in three hundred and five patients with ischemic stroke and 280 age and sex matched controls, using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing method. There were no significant differences in the genotype, allele and haplotype frequencies of P-selectin gene polymorphisms between the group of patients with ischemic stroke and the control group. Furthermore, there was no significant association of genotype, allele and haplotype at any of the polymorphism in relation to any subtype of ischemic stroke. We did not observe an association between P-selectin gene polymorphisms and ischemic stroke or any subtype of ischemic stroke. However, further studies are needed to explore the complex interaction between environmental factors and P-selectin gene polymorphisms in the risk of ischemic stroke, particularly in ethnically different populations.

The cytokine interleukin-8 (IL-8) may play a role in the pathogenesis of nasopharyngeal carcinoma (NPC) through the modulation of tumor immune response or enhanced angiogenesis. Polymorphism of IL-8 gene, which may affect the production level of cytokine, has been inversely associated with a number of cancers. To test this hypothesis, we investigated the relationship of IL-8 gene polymorphisms and NPC in a Chinese population. We analyzed single nucleotide polymorphisms (SNPs) of IL-8 gene − 845 T/C, − 738 T/A, − 353 A/T, − 251 A/T and + 678 T/C in 280 patients with NPC and 290 age and sex matched controls, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and polymerase chain reaction-sequence specific primers method (PCR-SSP). There were significant differences in the genotype and allele distribution of − 251 A/T polymorphism of the IL-8 gene among cases and controls. The − 251 AA and AT genotypes were associated with a significantly increased risk of NPC as compared with the − 251 TT genotypes (OR = 1.820, 95% CI, 1.120–2.959, P = 0.015 and OR = 1.590, 95% CI, 1.104–2.290, P = 0.013, respectively). Haplotype analysis revealed that the homozygosity of the AAT haplotype (defined by SNPs at positions − 353, − 251 and + 678) of IL-8 gene conveys the highest risk for NPC compared with the homozygosity for the TTC haplotype (OR = 1.396; 95% CI, 1.064–1.831; P = 0.016). The − 251 A/T polymorphism of IL-8 and its haplotype are associated with NPC in a Chinese population. Our data suggests that IL-8 gene may play a role in the development of NPC.

Objectives The objective of this study was to investigate the effects of slow breathing rate on heart rate variability (HRV) and blood pressure variability (BPV) in healthy subjects. Methods 53 healthy volunteers underwent three periods of controlled breathing at 8, 12 and 16 breaths/min. ECG (RR), respiratory and blood pressure signal were continuously and simultaneously recorded. In our study, the influence of the respiration on RRI (RR interval) and BP were observed. Simultaneously, we studied the effects of slow breathing rate on RRI, amplitude of blood pressure oscillation, low-frequency (LF) power, high-frequency (HF) power and LF/HF of HRV and BPV. Then we also corrected the effects of slow breathing rate on respiratory peak shifts. Results RRI and BP cyclical change coincided with the respiratory cycle; As breathing rate reduced, amplitude of RRI and blood pressure oscillation increased, heart rate slowed (P Conclusions Reductions of respiration rate shifted the respiratory peak into the junction of HF and LF or even below LF range. In accordance with this shift, the effects of slow breathing rate on respiratory peak shifts should be corrected when we performed HRV and BPV spectral analysis; Correct spectral analysis demonstrated that slow respiration can cause increase in HF power and decease in LF power and LF/HF. These demonstrated that slow breathing is indeed capable of increasing vagal activities and shifting sympathetic-vagal balance towards vagal activities.

Objectives To study the impact of respiratory frequency on HRV and discuss how to exclude it. Methods 12 healthy male rabbits aged 4-5 months and weighting 2.5-3.0 kg were selected. The Rabbits respiratory control system was established. ECG, instant blood pressure and respiratory waveform under different respiratory frequency (RF) (40 bpm,50 bpm,60 bpm) were recorded synchronously via SKY-A4 (a three channel electrophysiolograph); HRV & BRS2.0-a HRV analysis system was used to observe the shift of high frequency peak (HFP), and to analyse power spectra density (PSD). Two different analysis methods were adopted to analyse PSD, tHRV (traditional heart rate variability) analysis method with which parameters of different frequency segment were preset; EHRV (enhance heart rate variability) analysis method with which very low frequency were filtered, and HF were located near Fundamental Respiratory Frequency (FRF). Comparisons between the results of the two methods were made. Results The shift of HFP: RF 50 bpm, the HFP was located at the conjunction of LF segment and HF segment; RF 40 bpm, HFP would be shifted into the LF segment; RF 60 bpm, the total HFP would be shifted into HF segment. Comparison between tHRV and eHRV results: tHRV results:compared with RF 50 bmp, RF 40 bpm HF, HFnorm were decreased, LF, LFnorm, LF/HF were increased; RF 60 bpm seems increase HF (t =-3.477, P = 0.005), HFnorm (t =-2.903, P = 0.013), decrease LF/HF (t = 2.500, P = 0.028). eHRV results: there was no significant difference was fund between different RF PSD. Conclusions RF slow down would shift HFP to relatively low frequency, sometimes to LF segment, which would increase LF and decrease HF. Enhanced HRV analysis could exclude this influence.

Objectives To discuss the relationship between vagus nerve and heart rate variability (HRV). Methods 12 healthy rabbits were selected and anaesthetized, ventilation was used to control respiratory parameters, tide volume preset 10 mL/kg, respiratory frequency preset 50 beat per min, carotid compression transducer was used to monitor blood-pressure. ECGs of pre and post vagotomy were collected and analysed. Results RRI cyclical change pre and post vagotomy coincided with the respiratory cycle. Peak of RRI and respiratory power spectral density post vagotomy were shifted right (0.19 ± 0.02 vs 0.20 ± 0.03, P Conclusions Vagus nerve could affect respiratory sinus arrhythmia (RSA), but it was not the unique pathway attribute to RSA. High frequency power (HF) could reflect the function of vagus, but could not totally represent the tense of vagus nerve.

To assess the value of color Doppler ultrasound in distinguishing minimal pleural effusion from pleural thickening, a prospective analysis was done on the ultrasonographic findings in 51 patients. Real-time, gray-scale, and color Doppler chest ultrasound examinations were carried out by different sonographers who had no clinical information concerning the patients. The sonographer evaluated the images for internal echogenicity of the effusion, pleural lesions that change shape with respiration, and movable septa and echo-densities in pleural space in conventional gray-scale as well as color signal in color Doppler ultrasound. Of the 35 patients with true effusion, 33 had positive color signal (sensitivity 94.3%, 95% confidence intervals [CI] 89 to 98.6%); in 16 patients without effusion, none had color signal (specificity 100%, 95% CI 83 to 100%). Although real-time, gray-scale ultrasound is also sensitive for detecting minimal effusion (sensitivity 100%, 95% CI 92 to 100%), it is less specific (specificity 68.7%, 95% CI 46 to 91.5%). Five of 16 examinations showing fluid-like lesions were found to be deceptive. With relatively high sensitivity and specificity, this method proved to be a useful diagnostic aid to real-time, gray-scale ultrasound for diagnosis of minimal or loculated effusion.

BACKGROUND--Conservative treatment of malignant pericardial effusion by intrapericardial instillation of a sclerosing agent may be an alternative to surgery. METHODS--Twenty patients with malignant pericardial effusion were treated by ultrasound guided pericardiocentesis and the intrapericardial instillation of mitomycin C. RESULTS--Mitomycin C was effective in controlling the pericardial effusion in 70% of patients without causing side effects, except for pericardial constriction seven months later in one subject. CONCLUSIONS--Ultrasound guided intrapericardial instillation of mitomycin C is a suitable alternative in the management of malignant pericardial effusion.