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Wei He,1,2 Yao Luo,1 Jun-Peng Liu,1 Ning Sun,1 Di Guo,1 Ling-Ling Cui,1 Pei-Pei Zheng,1 Si-Min Yao,1 Jie-Fu Yang,1,2 Hua Wang1,2 1Department of Cardiology, Beijing Hospital, National Center of Gerontology, Beijing, People’s Republic of China; 2Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Hua Wang; Jie-Fu YangDepartment of Cardiology, Beijing Hospital, National Center of Gerontology, No. 1, Dahua Road, Dongcheng District, Beijing 100730, People’s Republic of ChinaTel +86 13911680467; +86 13601292259Fax +86 10-58115035Email wanghua2764@bjhmoh.cn; yangjiefu2011@126.comObjective: Our study aimed to explore the association between trimethylamine N-oxide and frailty in older adults with cardiovascular disease.Patients and Methods: This cross-sectional study analyzed a total of 451 people aged 65 years or older who underwent comprehensive geriatric assessments. Frailty status was determined using a frailty index constructed with 48 variables according to the cumulative deficits model. Physical frailty and cognitive frailty were also assessed in detail. Fasting plasma TMAO was measured by mass spectrometry.Results: The proportion of frail subjects was 29.9% (135/451). Plasma TMAO levels were significantly higher in frail patients than in nonfrail individuals (4.04 [2.84– 7.01] vs 3.21 [2.13– 5.03] μM; p< 0.001). Elevated plasma TMAO levels were independently associated with the likelihood of frailty (OR 2.12, 95% CI 1.01– 4.38, p=0.046). Dose–response analysis revealed a linear association between the TMAO concentration and the OR for frailty. A 2-unit increase in TMAO was independently correlated with physical frailty (OR 1.23, 95% CI 1.08– 1.41, p for trend 0.002) and cognitive frailty (OR 1.21, 95% CI 1.01– 1.45, p for trend 0.04).Conclusion: Elevated circulating TMAO levels are independently associated with frailty among older adults with cardiovascular disease.Keywords: older adults, frailty, TMAO, cardiovascular disease, physical frailty, cognitive frailty

He W, Luo Y, Liu JP, et al. Clin Interv Aging. 2020;15:1809– 1820. The authors have advised affiliation 2 on page 1809 is incorrect, the text “Peking Union Medical College” should read “Graduate School of Peking Union Medical College”. The authors apologize for this error.Read the original article

The efficient and economical removal of fermentation inhibitors from the complex system of biomass hydrolysate was one of the basics and keys in bio-chemical transformation. In this work, post-cross-linked hydrophilic-hydrophobic interpenetrating polymer networks (PMA/PS&#95;pc IPNs and PAM/PS&#95;pc IPNs) were proposed to remove fermentation inhibitors from sugarcane bagasse hydrolysate for the first time. PMA/PS&#95;pc and PAM/PS&#95;pc IPNs can obviously enhance the adsorption performance towards fermentation inhibitors due to their higher surface area and hydrophilic-hydrophobic synergetic surface properties, especially PMA/PS&#95;pc IPNs has higher selectivity coefficients of 4.57, 4.63, 4.85, 16.0, 49.43, and 22.69, and higher adsorption capacity of 24.7 mg/g, 39.2 mg/g, 52.4 mg/g, 9.1 mg/g, 13.2 mg/g, and 144.9 mg/g towards formic acid, acetic acid, levulinic acid (LA), 5-hydroxymethylfurfural (HMF), furfural, and acid-soluble lignin (ASL), respectively, in a lower total sugar loss of 2.03%. The adsorption kinetics and isotherm of PMA/PS&#95;pc IPNs were studied to elucidate its adsorption behavior towards fermentation inhibitors. In addition, the cyclic utilization property of PMA/PS&#95;pc IPNs was stable. Synthesizing PMA/PS&#95;pc IPNs is a new strategy to provide an efficient adsorbent for the removal of fermentation inhibitors from lignocellulosic hydrolysate., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Chemical stabilization of a high-pressure metastable state is a major challenge for the development of advanced materials. Although chemical pressure ( P chem ) can effectively simulate the effect of physical pressure ( P phy ), experimental calibration of the pressure passed to local structural motifs, denoted as local chemical pressure ( P chem- Δ ) which significantly governs the function of solid materials, remains absent due to the challenge of probing techniques. Here we establish an innovative methodology to experimentally calibrate the P chem- Δ and build a bridge between P chem and P phy via an optical probe strategy. Site-selective Bi 3+ -traced RE VO 4 ( RE  = Y, Gd) is adopted as a prototype to introduce Bi 3+ optical probes and on-site sense of the P chem- Δ experienced by the RE O 8 motif. The cell compression of RE 0.98 Bi 0.02 VO 4 under P phy is chemically simulated by smaller-ion substitution (Sc 3+ → RE 3+ ) in RE 0.98- x Sc x Bi 0.02 VO 4 . The consistent red shift ( Δλ ) of the emission spectra of Bi 3+ , which is dominated by locally pressure-induced RE O 8 dodecahedral variation in RE 0.98 Bi 0.02 VO 4 ( P phy ) and RE 0.98- x Sc x Bi 0.02 VO 4 ( P chem- Δ ), respectively, is evidence of their similar pressure-dependent local structure evolution. This innovative Δλ -based experimental calibration of P chem- Δ in the crystal-field dimension portrays the anisotropic transmission of P chem to the local structure and builds a bridge between P chem- Δ and P phy to guide a new perspective for affordable and practical interception of metastable states., (© The Author(s) 2023. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

Citrus Huanglongbing (HLB) is one of the most destructive diseases of citrus plants caused by the obligate and phloem-limiting bacterium Candidatus Liberibacter asiaticus (Las). Reliable detection methods are important for successful control of the disease. This study was aimed to develop a rapid and user-friendly on-site detection system for Las using the TaqMan probe-based insulated isothermal polymerase chain reaction (iiPCR) assay. The Las-specific on-site detection system could be completed within one hour by simple DNA extraction coupled with a portable POCKIT device, which can perform PCR amplification and automatically provide qualitative results derived from fluorescence signals. The sensitivity of the TaqMan probe-iiPCR assay could be as low as single copy of Las, comparable to a real-time PCR method. Further testing of the field citrus samples showed 100% agreement between the TaqMan probe-iiPCR assay and the real-time PCR method, and the on-site detection system also demonstrated a great performance of Las detection. With high specificity and sensitivity, the on-site detection system developed in this study becomes a simple, rapid and powerful tool for detecting Las in fields., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Yao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Co-contamination by heavy metal and organic pollutant may negatively influence plant performance, and increasing the number of genotypes for a plant population may reduce this negative effect. To test this hypothesis, we constructed experimental populations of Hydrocotyle vulgaris consisting of single, four or eight genotypes in soils contaminated by cadmium, cypermethrin or both. Biomass, leaf area and stem internode length of H. vulgaris were significantly lower in the soil contaminated by cypermethrin and by both cadmium and cypermethrin than in the soil contaminated by cadmium only. A reverse pattern was found for specific internode length and specific leaf area. In general, genotypic richness or its interaction with soil contamination did not influence plant growth or morphology. However, soil nutrients varied in response to soil contamination and genotypic richness. Moreover, plant population growth was positively correlated to soil total nitrogen, but negatively correlated to total potassium and organic matter. We conclude that co-contamination by cadmium and cypermethrin may suppress the growth of H. vulgaris population compared to contamination by cadmium only, but genotypic richness may play little role in regulating these effects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huang, Yao, Jin, Xue and Yu.)

Sophorolipids (SLs) are homologous microbial secondary metabolites produced by Starmerella bombicola and have been widely applied in many industrial fields. The biosynthesis of SLs is a highly aerobic process and is often limited by low dissolved oxygen (DO) levels. In this study, the Vitreoscilla hemoglobin (VHb) gene was transformed into S. bombicola O-13-1 by homologous recombination to alleviate oxygen limitation. VHb expression improved the intracellular oxygen utilization efficiency under either oxygen-rich or oxygen-limited conditions. In shake flask culture, the production of SLs was higher in the recombinant (VHb + ) strain than in the wild-type (VHb - ) strain, while the oxygen uptake rate of the recombinant (VHb + ) strain was significantly lower than that of the wild-type (VHb - ) strain. In a 5 L bioreactor, the production of SLs did not increase significantly, but the DO level in the fermentation broth of the VHb + strain was 21.8% higher than that of VHb - strain under oxygen-rich conditions. Compared to wide-type strains (VHb - ), VHb expression enhanced SLs production by 25.1% in the recombinants (VHb + ) under oxygen-limited conditions. In addition, VHb expression raised the transcription levels of key genes involved in the electron transfer chain ( NDH, SDH, COX ), TCA cycle ( CS , ICD , KDG1 ) and SL synthesis ( CYP52M1 and UGTA1 ) in the recombinant (VHb + ) strains. VHb expression in S. bombicola could enhance SLs biosynthesis and intracellular oxygen utilization efficiency by increasing ATP production and cellular respiration. Our findings highlight the potential use of VHb to improve the oxygen utilization efficiency of S. bombicola in the industrial-scale production of SLs using industrial and agricultural by-products like molasses and waste oil as fermentation feedstock., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Li, Yao, Zhao, Dong, Liang and Xu.)

Oxidative RNA damage has been found to be associated with age-related diseases and 8-oxo-7,8-dihydroguanosine (8-oxoGsn) is a typical marker of oxidative modification of RNA. Urine tests are a feasible non-invasive diagnostic modality. The present study aimed to assess whether the measurement of urinary 8-oxoGsn could represent a potential early maker in mild cognitive impairment (MCI) of frail patients with cardiovascular disease (CVD). In this cross-sectional study performed in China from September 2018 to February 2019. Urinary 8-oxoGsn was measured in frail (Fried phenotype: 3-5) in patients with CVD and was adjusted by urinary creatinine (Cre) levels. Cognitive function was assessed by the Chinese version of the Mini-Mental State Examination (MMSE) and participants were classified into non-MCI (≥24) and MCI (<24) groups. Univariate and multivariate logistic regression models were used to determine the relationship between 8-oxoGsn/Cre and MCI. Receiver operating characteristic (ROC) curve analysis was used to assess the 8-oxoGsn/Cre ratio in relation to MCI in frail patients with CVD. A total of 106 elderly patients were enrolled in this study. The mean age of participants was 77.9 ± 6.8 years, the overall prevalence of MCI was 22.6% (24/106), and 57.5% (61/106) of participants were women. In the multivariate logistic regression analysis, urinary 8-oxoGsn/Cre was independently associated with MCI (odds ratio [OR] = 1.769, 95% confidence interval [CI] = 1.234-2.536, P = 0.002), after adjusting for age, sex, education level, marital status, and serum prealbumin levels. The area under the ROC curve was 0.786 (0.679-0.893) ( P < 0.001), and the optimal cut-off value was 4.22 μmol/mol. The urinary 8-oxoGsn/Cre ratio showed a sensitivity of 87.5% and a specificity of 69.5%. The present study suggests the urinary 8-oxoGsn/Cre ratio may be a useful indicator for the early screening of MCI in frail patients with CVD., Clinical Trial Registration: ChiCTR1800017204; date of registration: 07/18/2018. URL: http://www.chictr.org.cn/showproj.aspx?proj=28931., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yao, Zheng, He, Cai, Wang and Yang.)

Background: The prevalence and prognostic value of heart failure (HF) stages among elderly hospitalized patients is unclear. Methods: We conducted a prospective, observational, multi-center, cohort study, including hospitalized patients with the sample size of 1,068; patients were age 65 years or more, able to cooperate with the assessment and to complete the echocardiogram. Two cardiologists classified all participants in various HF stages according to 2013 ACC/AHA HF staging guidelines. The outcome was rate of 1-year major adverse cardiovascular events (MACE). The Kaplan-Meier method and Cox proportional hazards models were used for survival analyses. Survival classification and regression tree analysis were used to determine the optimal cutoff of N-terminal pro-brain natriuretic peptide (NT-proBNP) to predict MACE. Results: Participants' mean age was 75.3 ± 6.88 years. Of them, 4.7% were healthy and without HF risk factors, 21.0% were stage A, 58.7% were stage B, and 15.6% were stage C/D. HF stages were associated with worsening 1-year survival without MACE (log-rank χ 2 = 69.62, P < 0.001). Deterioration from stage B to C/D was related to significant increases in HR (3.636, 95% CI, 2.174-6.098, P < 0.001). Patients with NT-proBNP levels over 280.45 pg/mL in stage B (HR 2; 95% CI 1.112-3.597; P = 0.021) and 11,111.5 pg/ml in stage C/D (HR 2.603, 95% CI 1.014-6.682; P = 0.047) experienced a high incidence of MACE adjusted for age, sex, and glomerular filtration rate. Conclusions : HF stage B, rather than stage A, was most common in elderly inpatients. NT-proBNP may help predict MACE in stage B. Trial Registration: ChiCTR1800017204; 07/18/2018., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zheng, Yao, Guo, Cui, Miao, Dong, Wang and Yang.)

Objective: Chronic inflammation is associated with major adverse cardiovascular events (MACEs), mortality, and frailty. Our aim was to add high-sensitivity C-reactive protein (hsCRP) to the frailty assessment to predict its association with prognosis of older adults with cardiovascular disease (CVD)., Methods: A comprehensive geriatric assessment was conducted at baseline in 720 in-patients aged ≥65 years with CVD. We divided the population into frailty and non-frailty groups according to the Fried phenotype, and hsCRP was further combined with frailty to stratify all patients into c-frailty and non-c-frailty groups. Predictive validity was tested using Cox proportional hazards regression model analysis and the discriminative ability was evaluated by receiver operating characteristic (ROC) curves., Results: Of all the subjects enrolled, 51.0% were male and the mean age was 75.32 ± 6.52 years. The all-cause death and MACE rate was 6.4% at the 1-year follow-up. Frailty and c-frailty were independent predictors of all-cause death and MACE (hazard ratio [HR]: 2.55, 95% confidence interval [CI]: 1.35-4.83, p = 0.004; HR: 3.67, 95% CI: 1.83-7.39, p < 0.001). Adding hsCRP to the frailty model resulted in a significant increase in the area under the ROC curve from 0.74 (95% CI: 0.70-0.77) to 0.77 (95% CI: 0.71-0.84) (p = 0.0132) and a net reclassification index of 7.9% (95% CI: 1.96%-12.56%, p = 0.012)., Conclusion: Adding hsCRP to the frailty assessment is helpful to identify a subgroup of older CVD patients with a higher risk of death and MACE over a period of 1 year., Trial Registration: ChiCTR1800017204; date of registration: 07/18/2018. URL: http://www.chictr.org.cn/showproj.aspx?proj=28931., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Multilocus variable-number tandem repeat analysis (MLVA) is widely used for genotyping of Bordetella pertussis, the causative bacteria for pertussis. However, MLVA genotyping is losing its discriminate power because prevalence of the epidemic MT27 strain (MLVA-27) is increasing worldwide. To address this, we developed a single nucleotide polymorphism (SNP) genotyping method for MT27 based on multiplexed single-base extension (SBE) assay. A total of 237 MT27 isolates collected in Japan during 1999-2018 were genotyped and classified into ten SNP genotypes (SG1 to SG10) with a Simpson's diversity index (DI) of 0.79 (95% CI 0.76-0.82). Temporal trends showed a marked increase in the genotypic diversity in the 2010s: Simpson's DI was zero in 1999-2004, 0.16 in 2005-2009, 0.83 in 2010-2014, and 0.76 in 2015-2018. This indicates that the SNP genotyping is applicable to the recently circulating MT27 strain. Additionally, almost all outbreak-associated MT27 isolates were classified into the same SNP genotypes for each outbreak. Multiplexed SBE assay allows for rapid and simple genotyping, indicating that the SNP genotyping can potentially be a useful tool for subtyping the B. pertussis MT27 strain in routine surveillance and outbreak investigations.

Background: Frailty increases the adverse outcomes of clinical heart failure; however, the relationship between frailty and stage-B heart failure (SBHF) remains unknown. We aimed to explore the epidemiology and predictive value of frailty in older adults with SBHF., Methods: A prospective cohort of SBHF inpatients aged 65 years or older who were hospitalized between September 2018 and February 2019 and were followed up for 6 months were included. SBHF was defined as systolic abnormality, structural abnormality (left ventricular enlargement, left ventricular hypertrophy, wall motion abnormalities, valvular heart disease), or prior myocardial infarction. Frailty was assessed by the Fried frailty phenotype. Multivariable Cox proportional hazards regression was used to explore the independent risk and prognostic factors., Results: Data of 443 participants (age: 76.1 ± 6.79 years, LVEF: 62.8 ± 4.92%, men: 225 [50.8%], frailty: 109 [24.6%]) were analyzed. During the 6-month follow-up, 83 (18.7%) older SBHF inpatients experienced all-cause mortality or readmission, and 29 (6.5%) of them developed clinical HF. Frail individuals had a 1.78-fold (95%CI: 1.02-3.10, P = 0.041) higher risk of 6-month mortality or readmission and a 2.83-fold (95%CI 1.24-6.47, P = 0.014) higher risk of developing clinical HF, independent of age, sex, left ventricular ejection fraction, and N-terminal pro-B-type natriuretic peptide level., Conclusions: Frailty is common in older SBHF inpatients and should be considered to help identify individuals with an increased risk of mortality or readmission, and developing clinical HF., Trial Registration: ChiCTR1800017204 .

Objective: To evaluate the prognostic value of frailty in gerontal pre-clinical heart failure (stage B heart failure, SBHF) inpatients. Background: The association between frailty and SBHF remains unknown. Methods: We conducted a subgroup analysis of a prospective observational cohort study on frailty. The previous study recruited 1,000 elderly inpatients who were consecutively admitted to a tertiary referral hospital in Beijing, China, from September 2018 to February 2019. The outcomes were all-cause death or readmission at 1-year follow-up. SBHF was diagnosed for asymptomatic cardiac structural or functional abnormalities. Frailty was assessed using the Comprehensive Geriatric Assessment-Frailty Index (CGA-FI). Results: Overall, 531 inpatients aged ≥65 years were deemed to have SBHF and followed up for 1 year. Of them, 34.5% exhibited frailty. During the follow-up period, all-cause death or readmission occurred in 157 (29.5%) participants. Of these participants, 36.6% (67/183) and 25.9% (90/348) belonged to the frail and non-frail groups, respectively (χ 2 = 6.655, P = 0.010). Frailty, defined by the CGA-FI, rather than Fried frailty phenotype, could independently predict 1-year all-cause death or readmission (hazard ratio, 1.56; 95% confidence interval, 1.03-2.35; P = 0.034) and was more suitable for predicting all-cause death or readmission than N-terminal pro-B-type natriuretic peptide in female SBHF inpatients aged 80 years or over(AUC CGA-FI vs. AUC NT-proBNP 0.654 vs. 0.575, P = 0.017). Conclusions: Frailty is highly prevalent even among SBHF inpatients aged ≥65 years. The CGA-FI can independently predict 1-year all-cause death or readmission, rather than Fried frailty phenotype. Frailty in gerontal SBHF inpatients deserves more attention. Clinical Trial registration: ChiCTR1800017204; date of registration: 07/18/2018., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Zheng, Yao, Shi, Wan, Guo, Cui, Sun, Wang and Yang.)

Objective: To investigate the predictive value of N-terminal type B natriuretic peptide（NT-proBNP) on the prognosis of elderly hospitalized patients without heart failure（non-heart failure). Method: Elderly patients aged 65 years or older, who were admitted to Beijing Hospital from September 2018 to February 2019, were enrolled in this study. Patients with clinical diagnosis of heart failure or left ventricular ejection fraction（LVEF)<50% were excluded. The patients were divided into 2 groups based on the serum NT-proBNP level: low NT-proBNP group （<125 ng/L) and high NT-proBNP group（≥125 ng/L). Patients were followed up at 3, 6, and 12 months after enrollment, and the major adverse events were recorded. The composite endpoint events included all-cause mortality, readmission or Emergency Department visits. Cardiovascular events include death, readmission or emergency room treatment due to cardiogenic shock, myocardial infarction, angina pectoris, arrhythmia, heart failure or stroke/transient ischemic attack. Results: A total of 600 elderly patients with non-heart failure were included in the analysis. The average age was （74.9±6.5) years, including 304（50.7%) males. The median follow-up time was 344（265, 359) days. One hundred and seventy-eight（29.7%) composite endpoint events were recorded during the follow-up, 19（3.2%) patients died, and 12（2.0%) patients were lost to follow-up. There were 286(47.7%) cases in low NT-proBNP group and 314 cases（52.3%) in high NT-proBNP group. Patients were older, prevalence of atrial fibrillation and myocardial infarction was higher; MMSE scores and ADL scores, albumin and creatinine clearance rate were lower in high NT-proBNP group than in low NT-proBNP group（all P <0.05). At 1-year follow-up, the incidence of composite endpoint events was significantly higher in high NT-proBNP group than in low NT-proBNP group（33.4%（105/314) vs. 24.8%（71/286), P = 0.02). Cardiovascular events were more common in high NT-proBNP group than in low NT-proBNP group（17.5%（55/314) vs. 8.4%（24/286), P = 0.001). Kaplan-Meier survival analysis showed both composite endpoint events（Log-rank P =0.016) and cardiovascular events（Log-rank P =0.001) were higher in high NT-proBNP group than in low NT-proBNP group. All-cause mortality was also significantly higher in highNT-proBNP group than in lowNT-proBNP group（4.8%（15/314) vs. 1.4%（4/286), P = 0.020), and Kaplan-Meier survival analysis demonstrated borderline statistical significance（Log-rank P = 0.052). Cox proportional hazard regression analysis showed that after adjusting for age, sex, creatinine clearance rate, myocardial infarction, and atrial fibrillation, NT-proBNP remained as an independent risk factor for composite endpoint events（ HR =1.376，95% CI 1.049-1.806, P =0.021), and cardiovascular events（ HR =1.777, 95% CI 1.185-2.664, P =0.005), but not for all-cause mortality（ P =0.206). Conclusions: NT-proBNP level at admission has important predictive value on rehospitalization and cardiovascular events for hospitalized elderly non-heart failure patients. NT-proBNP examination is helpful for risk stratification in this patient cohort.

Background: We aimed to assess the utility of the combination of the mini-mental state examination (MMSE) + clock drawing test (CDT) and the Fried phenotype for predicting non-elective hospital readmission or death within 6 months in elderly inpatients with cardiovascular disease (CVD)., Methods: A single-center prospective cohort was conducted from September 2018 to February 2019. Inpatients ≥65 years old were recruited. Predictive validity was tested using a Cox proportional hazards regression model analysis, and the discriminative ability was evaluated by the receiver operating characteristic (ROC) curve., Results: A total of 542 patients were included. Overall, 12% (64/542) screened positive for cognitive impairment, 16% (86/542) were physically frail and 8% (44/542) had cognitive impairment combined with physical frailty, showing an older age (P < 0.001) and a lower education level (P < 0.001) than physically frail patients. A total of 113 patients (20.9%) died or were readmitted at 6 months. Frail participants with a normal (hazard ratio [HR]: 1.73, 95% confidence interval [CI]: 1.06-2.82, P = 0.028) or impaired cognition (HR: 2.50, 95% CI: 1.27-4.91, P = 0.008) had a higher risk of non-elective hospital readmission or death than robust patients after adjusting for the age, sex, education level, marital status, the presence of diabetes mellitus, heart failure, and history of stroke. The area under the ROC curve (AUC) showed that the discriminative ability in relation to 6 months readmission and death for the MMSE + CDT + Fried phenotype was 0.65 (95% CI: 0.60-0.71), and the AUC for men was 0.71 (95% CI: 0.63-0.78), while that for women was 0.60 (95% CI: 0.51-0.69)., Conclusions: Accounting for cognitive impairment in the frailty phenotype may allow for the better prediction of non-elective hospital readmission or death in elderly inpatients with CVD in the short term., Trial Registration: ChiCTR1800017204; date of registration: 07/18/2018.

Connected ramets of aquatic clonal plants are susceptible to fragmentation by disturbance. Such clonal fragmentation may interact with nutrient availability and individual density to affect growth and morphology of aquatic clonal plants. We grew the widespread floating clonal plant Spirodela polyrhiza (duckweed) under three levels of population density (low, medium, or high), two levels of nutrient availability (low or high), and two levels of clonal fragmentation (with or without). Clonal fragmentation and high nutrients increased biomass and ramet number, but decreased frond width, frond length, and specific frond area of S. polyrhiza . Increasing population density decreased growth (biomass and ramet number) and frond and root size, and increased frond thickness of individual ramets of S. polyrhiza . The negative effect of population density on growth of S . polyrhiza was greater under high than under low nutrient availability. Furthermore, the negative effect of population density on total mass and frond mass of S. polyrhiza was greater with fragmentation than without. These results suggest that clonal fragmentation, nutrient availability and population density can interact to affect growth and morphology of clonal floating plants. Competition for nutrients and space, rather than light, may be the mechanisms underlying reduced growth of clonal floating plants. As clonal fragmentation can increase biomass and ramet production of S . polyrhiza , disturbance that potentially causes clonal fragmentation cannot be recommended as a measure to limit the spread of clonal floating plants., (Copyright © 2020 Zhang, Jin, Yao, Lei, Chen, Zhang and Yu.)

The diagnosis of frailty is usually subjective, which calls for objective biomarkers in clinical medicine. 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGsn) and 8-oxo-7, 8-dihydroguanosine (8-oxoGsn) in urine are two aging biomarkers that have not been explored deeply in cases of frailty. A total of 508 elderly patients with cardiovascular disease (mean age 75.0 ± 6.5 years, 50.8% males) were enrolled consecutively. Frailty was assessed by the Fried phenotype (robust: 0 score; pre-frail: 1-2 scores; frail: 3-5 scores). The concentrations of 8-oxoGsn and 8-oxodGsn in urine were measured by improved ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Urinary creatinine (Cre) was tested to correct the 8-oxoGsn and 8-oxodGsn levels. According to the Fried phenotype score, the proportions of robust, pre-frail, and frail subjects were 20.5% (104/508), 53.9% (274/508), and 25.6% (130/508), respectively. The urinary 8-oxoGsn/Cre (P < 0.001) differed significantly among these 3 groups, but the urinary 8-oxodGsn/Cre (P = 0.600) showed no marked difference. Univariate and multivariate logistic regression showed that the age (odds ratio [OR] = 1.090, P < 0.001), systolic blood pressure (OR = 0.981, P = 0.008), 8-oxoGsn/Cre (OR = 1.203, P = 0.007), hemoglobin (OR = 0.980, P = 0.007), and sodium (OR = 0.915, P = 0.044) were independently associated with frailty. The sensitivity and specificity to identify frailty were 53.08% and 71.96%, respectively, for 8-oxoGsn/Cre at the optimal cut-off value of 3.879 μmol/mol according to the maximal Youden index. Urinary 8-oxoGsn, as a recognized biomarker of RNA oxidation, is independently associated with frailty in elderly patients with cardiovascular disease. However, the urinary 8-oxodGsn shows no obvious correlation with frailty. To obtain a better diagnostic performance for frailty, more biomarkers from different pathophysiological pathways should be explored in the future., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2020. Published by Elsevier Inc.)

Purpose. Human-adapted Bordetella parapertussis is one of the causative agents of whooping cough; however, there are currently no genotyping systems with high discriminatory power for this bacterial pathogen. We therefore aimed to develop a multilocus variable-number tandem repeat analysis (MLVA) for human-adapted B. parapertussis . Methodology. Four highly polymorphic variable number tandem repeat (VNTR) loci in the B. parapertussis genome were selected and amplified by multiplex PCR. MLVA was performed based on the number of tandem repeats at VNTR loci. The discriminatory power of MLVA was evaluated with three laboratory reference strains and 50 human isolates of B. parapertussis . Results. Multiplex PCR-based MLVA characterized 53 B. parapertussis reference strains and isolates into 25 MLVA types and the Simpson diversity index was 0.91 (95 % confidence interval, 0.86-0.97). The three reference strains exhibited different MLVA types. Thirty-one Japanese isolates, ten French isolates and three Taiwanese isolates belonged to fourteen, nine and three MLVA types, respectively. In contrast, all five Australian isolates belonged to the same type. Two Japanese isolates collected from patients with known epidemiological links had the same type. Conclusion. Our novel MLVA method has high discriminatory power for genotyping human B. parapertussis . Regarding this organism, this genotyping system is a promising tool for epidemiological surveillance and investigating outbreaks.

Background: Streptococcus pneumoniae infections in Taiwan mostly occur in children aged 2-4 years. Because of a significant increase in the incidence of serotype 19A-related infections, the 13-valent pneumococcal conjugate vaccine (PCV13) was initially introduced in the national immunization program for children 2-5 years of age, prior to the national programs for infants. We have assessed the impact of such vaccination programs in reducing the incidence of invasive pneumococcal disease (IPD) in Taiwanese children., Methods: We analyzed the national data on IPDs from the Taiwan Centers for Disease Control between 2008 and 2017. We calculated the incidence rates of IPD and incidence rate ratios (IRRs) between years for different serotypes to estimate the effectiveness of the vaccination programs., Results: The national catch-up primary vaccination schedule successfully reduced the incidence rate of IPD from 17.8/100 000 in 2012 to 5.5/100 000 in 2017 among children aged 0-5 years. The IRR (2017 over 2012) was 0.31, corresponding to a 69% reduction. A modest herd effect was also observed, with a 37% reduction in the incidence of IPD in elderly people (≥70 years) from 2012 to 2017. The incidence of IPD caused by serotype 19A in children aged 0-5 years was reduced by 32.6-44.3% yearly from 2012 to 2017. In 2015, serogroup 15 outnumbered 19A, to become the leading serotypes in children 0-5 years old., Conclusions: Special catch-up vaccination programs starting from children 2-5 years of age with PCV13 have been highly effective in reducing the incidence of IPD, especially as caused by serotype 19A, in Taiwanese children., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Caveolin-1 (Cav-1), as a membrane protein involved in the formation of caveolae, binds steroid receptors and endothelial nitric oxide synthase, limiting its translocation and activation. In the present study, we investigated the role of Cav-1 in the progression of hepatic fibrosis induced by carbon tetrachloride (CCl 4 ) in murine animals. Therefore, the wild type (WT) and Cav-1-knockout (Cav-1 -/- ) mice were used in our study and subjected to CCl 4 . The results indicated that CCl 4 induced the decrease of Cav-1 expression in liver tissue samples. And Cav-1 -/- intensified CCl 4 -triggered hepatic injury, evidenced by the stronger hepatic histological alterations, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and liver terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells. CCl 4 led to oxidative stress, supported by the reduced superoxide dismutase (SOD) activity and glutathione (GSH) levels, as well as enhanced malondialdehyde (MDA) and O 2 - levels in liver samples. And the process was intensified by Cav-1 -/- . Additionally, CCl 4 -caused hepatic inflammation was aggregated by Cav-1 -/- via further increasing the secretion of pro-inflammatory cytokines. Moreover, CCl 4 -caused fibrosis was strengthened by Cav-1 -/- , which was evidenced by the up-regulation of α-smooth muscle actin (α-SMA), collagen alpha 1 type 1 (Col1A1), lysyl oxidase (Lox) and transforming growth factor-β1 (TGF-β1) in liver tissues. Similar results were observed in TGF-β1-stimulated hepatic stellate cells (HSCs) and LX-2 cells without Cav-1 expressions that in vitro, suppressing Cav-1 further accelerated TGF-β1-induced oxidative stress, inflammation and fibrosis development. In conclusion, our results indicated that Cav-1 played an important role in CCl 4 -induced hepatic injury, which may be used as potential therapeutic target for hepatic fibrosis treatment., (Copyright © 2018. Published by Elsevier Masson SAS.)

Speckle-type POZ domain protein (SPOP) has been acknowledged as a tumor suppressor gene in numerous types of cancer. However, SPOP expression and its prognostic role in human non-small cell lung cancer (NSCLC) remain unknown. The present study investigated SPOP expression in NSCLC and evaluated its prognostic significance in patients with NSCLC. The results demonstrated that SPOP expression was significantly downregulated in NSCLC tissues at the mRNA and protein level compared with normal lung tissues using reverse transcription-quantitative polymerase chain reaction, and western blot analysis. Immunohistochemical staining results also demonstrated that SPOP was expressed at a low level in 84.1% (132/157) of NSCLC samples and at a high level in 52.2% (12/23) of normal lung samples, whereby the difference was statistically significant (P<0.001). In addition, it was revealed that the level of SPOP was associated with histologic type (P=0.003), tumor differentiation (P=0.046), tumor size (P=0.0036), lymph node metastasis (P=0.041) and clinical stages (P=0.046). Furthermore, the overall survival of patients with high SPOP expression was significantly increased compared with that of patients with low SPOP expression (P=0.003). These results revealed that SPOP expression was downregulated in NSCLC tissues and associated with poor prognosis in patients with NSCLC, suggesting that SPOP is an independent prognostic marker candidate for NSCLC.

Aim: To investigate the combined diagnostic accuracy of acoustic radiation force impulse (ARFI), aspartate aminotransferase to platelet ratio index (APRI) and Forns index for a non-invasive assessment of liver fibrosis in patients with chronic hepatitis B (CHB)., Methods: In this prospective study, 206 patients had CHB with liver fibrosis stages F0-F4 classified by METAVIR and 40 were healthy volunteers were measured by ARFI, APRI and Forns index separately or combined as indicated., Results: ARFI, APRI or Forns index demonstrated a significant correlation with the histological stage (all P < 0.001). According to the AUROC of ARFI and APRI for evaluating fibrotic stages more than F2, ARFI showed an enhanced diagnostic accuracy than APRI (P < 0.05). The combined measurement of ARFI and APRI exhibited better accuracy than ARFI alone when evaluating ≥ F2 fibrotic stage (Z = 2.77, P = 0.006). Combination of ARFI, APRI and Forns index did not obviously improve the diagnostic accuracy compared to the combination of ARFI and APRI (Z = 0.958, P = 0.338)., Conclusion: ARFI + APRI showed enhanced diagnostic accuracy than ARFI or APRI alone for significant liver fibrosis and ARFI + APRI + Forns index shows the same effect with ARFI + APRI.

Background: Cancer is a burden on humanity and ranks as a leading cause of morbidity and mortality in China. Shanxi province has its unique cancer patterns and the burden is increasing. In this study, we aimed to assess the pattern of dietary habits and life-style in Shanxi, a high-risk area for upper gastrointestinal cancers in China and further evaluate the trends in cancer incidence and mortality based on registered data., Materials and Methods: Data on lifestyle, diet, physical activity were obtained from the household health survey at Zhongyang from 2013 to 2015. Cancer diagnoses were reported to Shanxi Center for Disease Control and Prevention (SCDCP). Population-based cancer incidence data and mortality data of 2012 were collected from the SCDCP. All incidence and death rates were expressed per 100,000 populations. Univariate analysis was performed using the Chi-squared test or Fisherandapos;s exact test., Results: Overall, deficiencies in fresh fruits and vegetable food, and intake of hot food, salted food, or pickled food are serious problems in Shanxi, especially in rural areas. Upper gastrointestinal cancers were the most commonly diagnosed cancers, and the incidence in rural areas is higher than those in urban areas. Cervical cancer is the most common cancer for females. Moreover, the agespecific incidence exhibited an increased trend before 40 years old. Consistent with the previous literature, our epidemiological investigation results suggest that lifestyle, nutrition deficient, and infections were major risk factors for upper gastrointestinal cancers or cervical cancer in Shanxi. Facing a serious situation, we further explored defensible recommendations for the general public in order to promote changes in environments that support healthful eating and physical activity habits, to reduce cancer risk., Conclusions: Our results present the current cancer trends in Shanxi and its related etiologic risk factors and provide a theoretical basis to guide public health efforts to prevent and control cancers in the province.

Background: Cognitive behavioural therapy (CBT) is an effective treatment for obsessive-compulsive disorder (OCD). Several neuroimaging studies have explored alterations of brain function in OCD patients as they performed tasks after CBT. However, the effects of CBT on the neural activityin OCD during rest remain unknown. Therefore, we investigated changes in regional homogeneity (ReHo) in OCD patients before and after CBT., Methods: Twenty-two OCD patients and 22 well-matched healthy controls participated in the resting-state functional magnetic resonance imaging scans. We compared differences in ReHo between the OCD and control groups before treatment and investigated the changes of ReHo in 17 OCD patients who responded to CBT., Results: Compared to healthy controls, OCD patients exhibited higher ReHo in the right orbitofrontal cortex (OFC), bilateral middle frontal cortex, right precuneus, left cerebellum, and vermis, as well as lower ReHo in the bilateral caudate, right calcarine, right posterior cingulate cortex, and right middle temporal cortex. Along with the clinical improvement in OCD patients after CBT, we found decreased ReHo in the right OFC, bilateral middle frontal cortex, left cerebellum and vermis, and increased ReHo in the left caudate. Improvement of OCD symptoms was significantly correlated with the changed ReHo in the right OFC and left cerebellum., Conclusions: Although these findings are preliminary and need to be replicated in larger samples, they indicate the presence of abnormal spontaneous brain activity of the prefrontal-striatal-cerebellar circuit in OCD patients, and provide evidence that CBT can selectively modulate the spontaneous brain activity of this circuit in OCD patients., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Although staffs in medical colleges have traditionally been characterized as a stressed group of people, there are no specific studies assessing burnout and the relationship to quality of life (QOL). The purpose of this cross-sectional study was to evaluate job-related burnout and the relationship to QOL among medical college staff in mainland China. Some 360 medical college staffs from 15 schools and departments were enrolled in the study. The Chinese Teachers' Burnout Inventory (TBI) and the World Health Organization Quality of Life--brief Chinese version were used. Data on sociodemographic, work-related, and health-related factors were also collected. Multiple stepwise regression analysis was used to identify significant factors related to the 3 domain scores of the TBI. Structural equation modeling was performed to test the correlation between job-related burnout and QOL. The most significant and common predictors of burnout prevention were a love of the teaching profession and work acknowledgment from a direct supervisor. Job-related burnout had a direct negative effect on QOL. Corresponding health policies and suggestions could be developed to prevent job-related burnout and improve QOL.

Objective: To compare the efficacy differences between dog-days medicinal vesiculation and regular-day medicinal vesiculation for perennial allergic rhinitis (PAR), and observe their effects on serum immune globulin E (IgE) and interleukin-4 (IL-4)., Methods: Seventy-two patients were randomly divided into a dog-days moxibustion group (34 cases) and a regular-day moxibustion group (38 cases). In the dog-days moxibustion group, medicinal vesiculation was applied on the 1st dog-day, 2nd dog-day and last dog-day in summer by lunar calendar, 3 treatments per dog-day for totally 9 times. In the regular-day moxibustion group, the moxibustion was given on the regular day for continuous 9 times. The symptom score, rhinoconjunctivitis quality of life questionnaire (RQLQ) and the level of IgE and IL-4 were compared before and after treatment in two groups; the short-term and two-year efficacy evaluation were performed too., Results: The short-term total effective rate was 88.2% (30/34) in the dog-days moxibustion group, which was not significantly different to 86.8% (33/38) in the regular-day moxibustion group (P>0.05). The long-term total effective rate was 97.1% (33/34) in the dog-days moxibustion group, which was significantly superior to 81.6% (31/38) in the regular-day moxibustion group (P<0.05). After treatment, the serum IgE, IL-4 and RQLQ were significantly reduced (all P<0.01), but the difference between two groups was not significant (all P>0.05)., Conclusion: Medicinal moxibustion could be taken as a regular treatment for PAR, which could be performed during the whole year, and dog-days moxibustion could be considered as an enhanced method for prevention and treatment of PAR.

Affective states influence subsequent attention allocation. We evaluated emotional negativity bias modulation by reappraisal in patients with generalized anxiety disorder (GAD) relative to normal controls. Event-related potential (ERP) recordings were obtained, and changes in P200 and P300 amplitudes in response to negative or neutral words were noted after decreasing negative emotion or establishing a neutral condition. We found that in GAD patients only, the mean P200 amplitude after negative word presentation was much higher than after the presentation of neutral words. In normal controls, after downregulation of negative emotion, the mean P300 amplitude in response to negative words was much lower than after neutral words, and this was significant in both the left and right regions. In GAD patients, the negative bias remained prominent and was not affected by reappraisal at the early stage. Reappraisal was observed to have a lateralized effect at the late stage.

Introduction: Serotype replacement after the introduction of seven-valent pneumococcal conjugate vaccine (PCV7) and the future availability of multivalent PCVs prompted the listing of invasive pneumococcal disease (IPD) as a notifiable disease in Taiwan in October 2007. Here, we report the national surveillance results., Methods: The study population comprised the whole nation of Taiwan from 2008 to 2012. Restricting to cases with viable isolates, we calculated the incidence, case fatality ratio, prevalence of serotype 19A, and percentage of vaccine preventable IPD., Results: 3659 cases of IPD were identified yielding an incidence of 3.2 per 100,000 population; the highest incidence was among children aged 2-4 years (21.1 per 100,000 population). The case fatality ratio was 9.2% and the highest ratio was among adults aged ≥75 years (19.0%). The percentage of PCV7 preventable IPD decreased for all age groups, especially sharply among children aged 2-4 years, from 65.8% in 2008 to 12.9% in 2012. The prevalence of serotype 19A increased from 5.5% in 2008 to 25.3% in 2012 among all Streptococcus pneumoniae, displaying a differential temporal emergence among different age groups. Serotype 19A became the most prevalent serotype among children aged <2 years in 2009, children aged 2-4 and 5-17 years in 2010, and adults aged 18-49 years in 2012., Conclusions: The incidence of IPD fluctuated during the study period, with ongoing decrease due to PCV7 vaccine serotypes and increase due to non-vaccine serotypes. Serotype 19A became the most prevalent serotype in 2010 among all S. pneumoniae., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Bordetella pertussis causes pertussis, a respiratory disease that is most severe for infants. Vaccination was introduced in the 1950s, and in recent years, a resurgence of disease was observed worldwide, with significant mortality in infants. Possible causes for this include the switch from whole-cell vaccines (WCVs) to less effective acellular vaccines (ACVs), waning immunity, and pathogen adaptation. Pathogen adaptation is suggested by antigenic divergence between vaccine strains and circulating strains and by the emergence of strains with increased pertussis toxin production. We applied comparative genomics to a worldwide collection of 343 B. pertussis strains isolated between 1920 and 2010. The global phylogeny showed two deep branches; the largest of these contained 98% of all strains, and its expansion correlated temporally with the first descriptions of pertussis outbreaks in Europe in the 16th century. We found little evidence of recent geographical clustering of the strains within this lineage, suggesting rapid strain flow between countries. We observed that changes in genes encoding proteins implicated in protective immunity that are included in ACVs occurred after the introduction of WCVs but before the switch to ACVs. Furthermore, our analyses consistently suggested that virulence-associated genes and genes coding for surface-exposed proteins were involved in adaptation. However, many of the putative adaptive loci identified have a physiological role, and further studies of these loci may reveal less obvious ways in which B. pertussis and the host interact. This work provides insight into ways in which pathogens may adapt to vaccination and suggests ways to improve pertussis vaccines. IMPORTANCE Whooping cough is mainly caused by Bordetella pertussis, and current vaccines are targeted against this organism. Recently, there have been increasing outbreaks of whooping cough, even where vaccine coverage is high. Analysis of the genomes of 343 B. pertussis isolates from around the world over the last 100 years suggests that the organism has emerged within the last 500 years, consistent with historical records. We show that global transmission of new strains is very rapid and that the worldwide population of B. pertussis is evolving in response to vaccine introduction, potentially enabling vaccine escape.

Objective: To express soluble HA of A/H1N1 influenza virus in drosophila S2 cell line and identify its bio-activity., Methods: HA gene was amplified from A/Shenzhen/71/09 virus strain using RT-PCR, then we constructed pAC5.1-HA expression vector, which was co-transfected into S2 cell with pCoblast vector. After transfection, stable S2 cell was selected through Blasticindin. HA in the supernatant was identified with Western Blot assay and purified with Ni-column. Recombinant HA was immunized into BALB/c mice 3 times, and the Abs titers were evaluated with ELISA., Results: We successfully cloned HA gene with 1.7 x 10(3) bp of A/Shenzhen/71/09 virus strain and got recombinant pAC5. 1-HA expression vector. Stable S2 cell line was established after transfection and selection, which continuously expressed HA with molecular weight 75 x 10(3) D. After immunization with HA, the Abs titers were 1:1280 and 1: 5120 respectively on 10 d, 30 d., Conclusion: We expressed soluble HA with good bio-activity, which contributed to research on immune diagnosis, subunit vaccine, and monoclonal Abs for influenza.

Taking wheat cultivar Bainong AK58 as test material, a field experiment was conducted to study the plant nitrogen accumulation and translocation and kernel protein content of winter wheat under sprinkler irrigation and surface irrigation, aimed to understand the differences in the nitrogen metabolism characteristics of winter wheat under different irrigation regimes. At booting stage, no significant difference was observed in the total amount of plant nitrogen accumulation between sprinkler irrigation and surface irrigation; while from booting stage to maturing stage, the total amount of plant nitrogen accumulation under sprinkler irrigation was significantly higher. Under sprinkler irrigation, the translocation amount and contribution rate of the nitrogen stored in leaf, glume, stem and sheath at pre-anthesis to the kernel increased, while the contribution rate of the assimilated nitrogen after anthesis to the kernel nitrogen declined. Both the relative protein content and the total protein yield in the kernel increased significantly under sprinkler irrigation. In conclusion, sprinkler irrigation could significantly regulate the nitrogen translocation and kernel protein accumulation of winter wheat.

Objective: This study aimed at evaluating the efficacy and safety of a combination treatment of entecavir and Peginterferon alpha-2a for HBeAg positive chronic hepatitis B patients with high serum hepatitis B viral loads., Methods: 60 treatment-naive HBeAg-positive CHB patients with high serum hepatitis B viral loads were enrolled and randomly divided into three groups: group A received Peginterferon alpha-2a monotherapy for 48 weeks (n = 20); group B received entecavir monotherapy for more than 48 weeks (n = 20); group C received Peginterferona alpha-2a combined with entecavir for 12 weeks, then Peginterferon alpha-2a monotherapy for 36 weeks (n = 20). Virological response, ALT normalization, HBeAg and HBsAg seroclearance rate were analysed at the end of 4, 12 and 24 weeks after the treatment., Results: The ratio of undetectable hepatitis B virus (HBV) DNA were 50% and 10%, 95% and 25% and 100% and 30% in group C and group A respectively, 50% and 20%, 95% and 75% and 100% and 90% in group C and group B respectively at the end of 4, 12 and 24 weeks of treatment. The differences were significant between group C and A (Z = -4.6, P < 0.001), group C and B (Z = -2.53, P = 0.0114). ALT normalization rate was significantly lower in group A than that of group C (Z = -2.63, P = 0.0086). HBeAg levels declined more in group C than the other two groups after 24 weeks of treatment., Conclusions: For HBeAg positive chronic hepatitis B patients with high serum hepatitis B viral loads, combination treament of Peginterferon alpha-2a with entecavir is more effective than Peginterferon alpha-2a monotherapy in virologic response and ALT normalization after 24 weeks of treatment.

Taking wheat cultivar Bainong AK58 as test material, a field experiment was conducted to study the effects of different concentration 5-aminolevulinic acid (ALA) (0,10, 30 and 50 mg x L(-1)) applied at initial heading stage on the post-anthesis dry matter accumulation and flag leaf senescence of the cultivar. Applying 10-50 mg x L(-1) of ALA benefited the dry matter accumulation, with its total amount at maturing stage being significantly higher than that of the control (0 mg x L(-1) ALA). 10-50 mg x L(-1) of ALA had no significant effects on the distribution of accumulated dry matter in leaf, stem and sheath, and grain, but increased the contribution of the dry matter to grain yield. 10-50 mg x L(-1) of ALA increased the leaf area index at milky and dough stages, but had no effects on it at flowering stage. After treated with 10-50 mg x L(-1) ALA, the leaf SPAD value and net photosynthetic rate from anthesis to milky stage were significantly higher, and the MDA content and relative electric conductivity at later grain-filling stage were lower, compared with those of the control. Applying 10-50 mg x L(-1) of ALA increased the grain number per spike, 1000-grain mass, and grain yield significantly, with the best effect when applying 30 mg x L(-1) ALA.

Objective: To explore the association between HBV genotyping and clinical characteristics and expression of TH1/TH2 cytokines., Methods: The expression of IL-4 and IFN-gamma was detected with flow cytometry for 102 HBV infections and 48 healthy controls. 50 CHB patients were randomly selected for HBV genotyping with real-time fluorescence PCR assay., Results: Higher expression of IL-4 in peripheral blood was detected in patients with HBV infection than healthy controls (P < 0.001); No significant differences on expression of Th1/Th2 cytokines were observed in CHB patients with different HBV DNA levels or HBeAg status (P > 0.05). There were 34 (68%) patients with genotype B infection and 16 (32%) with genotype C infection. Compared to patients with genotype B infection, the patients with genotype C infection showed higher levels of IL-4 (P = 0.018), and Th1/Th2 ratio decreased,but the difference was not statistically significant (P = 0.2262)., Conclusion: The different expression of TH1/TH2 cytokines may elucidate cellular immune response and clinical outcome difference between patients with genotype B infection and genotype C infection.

Objective: To study the clinical features of acquired immune deficiency syndrome (AIDS) complicated with tuberculosis of mesenteric lymph nodes., Methods: Cases (n = 153) with AIDS complicated with tuberculosis hospitalized in this hospital from September 1999 to December 2008 were retrospectively analyzed. Mesenteric lymph node tuberculosis was found in 11 cases, including 7 males and 4 females. One patient was 8 years old, and the other 10 were over 22 years (ranging from 8 to 55 years)., Results: In patients with AIDS complicated with tuberculosis, 7% (11/158) had tuberculosis of the mesenteric lymph nodes. The CD(4)(+) cell count was less than 50 x 10(6) cells/L in 8 cases, and (50 - 100) x 10(6) cells/L in 3 cases. The symptoms included fever (11/11), abdominal pain (11/11), abdominal distension (11/11), night sweat (7/11), weight loss (10/11), diarrhea (7/11), anemia (5/11), abdominal mass (3/11), and ascites (1/11). Abdominal ultrasound showed multiple enlarged mesenteric lymph nodes in all of the 11 cases, and abdominal CT scanning presented typical enhanced ring shadows. Biopsy of mesenteric lymph nodes was obtained from 2 cases, and both revealed tuberculoma, caseous necrosis. Longerhan cell infiltration, and positive stain for fast anti-acid bacilli. Enlarged mesenteric lymph nodes became smaller and disappeared after treatment with antituberculous drugs for 6 months and highly active antiretroviral therapy (HAART) for 5 months in all the 11 patients., Conclusions: There were no specific clinical manifestations in AIDS patients with tuberculosis of mesenteric lymph nodes. However, AIDS patients with CD(4)(+) cell count less than 50 x 10(6) cells/L might be more prone to developing tuberculosis of the mesenteric lymph nodes. Abdominal CT scanning with typical strengthened ring shadow is suggestive of the diagnosis. Anti-tuberculous therapy combined with HAART is recommended for the treatment of patients with suspected tuberculosis.

In the title compound, C(9)H(9)BrO(3), the dihedral angle between the ethanone group and the aromatic ring is 3.6 (2)°. The mol-ecular conformation is consolidated by an intra-molecular O-H⋯O hydrogen bond. The crystal structure is stabilized by π-π inter-actions between the benzene rings [centroid-centroid distance = 3.588 (2) Å].

In Taiwan, pertussis is a notifiable disease with a low incidence in recent years, and antimicrobial susceptibility testing for the causative agent, Bordetella pertussis, has not been reported to date. In May 2007, the Centers for Disease Control, Taiwan, was informed of a 1-month-old pertussis patient who did not respond to erythromycin treatment. In this study, we report the result of antimicrobial susceptibility testing performed for the suspected erythromycin-resistant isolate, as well as for an additional 27 B. pertussis clinical isolates that represented almost all epidemiologically unrelated isolates obtained throughout Taiwan between 2003 and 2007. All isolates were fully susceptible to azithromycin, erythromycin, clarithromycin and trimethoprim/sulfamethoxazole (MIC < or =0.047 mug ml(-1)). This result demonstrates the general susceptibility of B. pertussis to antimicrobial agents in vitro in Taiwan.

Objective: To investigate the possible association between residual sleepiness (RS) and central sleep apnea events in patients with obstructive sleep apnea syndrome (OSAS) following continuous positive airway pressure (CPAP) treatment, as well as the effects of adaptive servo-ventilation (ASV) on RS., Methods: Following correct application of CPAP treatment and exclusion of other sleepiness-associated disorders, 50 patients with moderate-to-severe OSAS were recruited, including 26 patients with RS (RS group) and 24 patients without RS (control group). The treatment of one month's auto-CPAP (AutoCPAP) followed by one week ASV with autoCS2 ventilator was performed. Comparisons were made separately before treatment, on AutoCPAP and ASV treatments in both groups of the following parameters: polysomnographic parameters including central sleep apnea index (CSAI), micro-arousal index (MAI), etc; daytime Epworth sleepiness score (ESS), and possibly sleepiness-associated factor, i.e., plasma tumor necrosis factor-alpha (TNF-alpha). Plasma TNF-alpha levels were measured by enzyme linked immunosorbent assay (ELISA). t test and single factor analysis of variances were used for comparison between two groups and within group respectively. q test was used for couple comparison within group at 3 different stages. Pearson correlation test was performed for correlation analysis between 2 variables., Results: Before treatment there was no significant difference between two groups in apnea hypopnea index (AHI), MAI, minimal pulse oxygen saturation (minSpO2), ESS and plasma TNF-alpha levels (t: 0.630, 1.223, 0.691, 0.764 and 0.19 2, all P > 0.05). However, the CSAI in RS group was significantly higher than that in the control group [(7.19 +/- 1.75) times/h vs (3.37 +/- 1.04) times/h, t = 4.097, P < 0.05)]. After 1 month's AutoCPAP treatment there was a significant decrease in AHI, CSAI, MAI and ESS in both groups (q: 0.87-112.55, all P < 0.05), but CSAI, MAI and ESS in the RS group than those in the control group [CSAI: (7.19 +/- 1.75) times/h vs (3.37 +/- 1.04) times/h, t = 9.473, P < 0.05; MAI: (9.00 +/- 1.95) times/h vs (2.36 +/- 0.66) times/h, t = 14.385, P < 0.05; ESS: 9.54 +/- 0.51 vs 5.42 +/- 1.32, t = 2.857, P < 0.05). On one weeks' ASV treatment there was such a further significant decrease in CSAI, MAI and daytime ESS in the RS group and the control group. In addition, compared with the plasma TNF-alpha level before treatment in the RS group, there was no statistical difference on AutoCPAP treatment but a significant decrease on ASV treatment. Plasma TNF-alpha levels were positively correlated with ESS (r = 0.503, P < 0.01) and MAI (r = 0.545, P < 0.01)., Conclusions: RS in OSAS patients following CPAP treatment was associated with their CSAI before and during treatment. By effectively eliminating CSA events with ASV, RS was significantly improved, which suggested that ASV was effective in treatment of RS. The elevation of plasma TNF-alpha level was correlated with the severity of sleepiness and may be involved in the pathogenesis of RS.

We investigated the mechanisms involved in imipenem resistance in 23 clinical strains of Acinetobacter baumannii. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed the presence of a 30-kDa protein in imipenem-intermediate A. baumannii (IIAB) and imipenem-resistant A. baumannii (IRAB) strains; this protein was almost undetectable in imipenem-susceptible A. baumannii (ISAB) strains. The 30-kDa protein was identified as an OXA-51-like carbapenemase using two-dimensional gel electrophoresis and mass spectrometry. Similar to other recent findings, bla(OXA-51-like) genes were found to exist in all 23 clinical strains; however, the transcript levels of bla(OXA-51-like) in the IIAB and IRAB were higher than in the ISAB strains using reverse transcriptase PCR (RT-PCR) and real-time RT-PCR assays. This change was due to the presence of an insertion sequence, ISAba1, upstream of bla(OXA-51-like) in the IIAB and IRAB strains that was not present in the ISAB strains. The introduction of bla(OXA-66) (a bla(OXA-51)(-like) gene), identified in ISAB ab1254 and IRAB ab1266, into Escherichia coli TOP10 cells resulted in 3.95-fold and 7.90-fold elevations in resistance to imipenem, respectively. Furthermore, when ISAB ab8 and ISAB ab1254 and their in vitro-selected imipenem-resistant mutants ISAB ab8(r) and ISAB ab1254(r) were compared, the results showed no change in the bla(OXA-66)/bla(OXA-51-like) gene sequences, in expression of the gene, and in the outer membrane protein profiles. However, there was a four- to eightfold reduction in imipenem resistance upon adding carbonyl cyanide m-chlorophenylhydrazone. Taken together, these results suggest that the OXA-66/OXA-51-like carbapenemase contributes to intrinsic resistance to imipenem; however, drug export by an efflux pump may be more important and/or occur more frequently in imipenem-resistant A. baumannii. Furthermore, this is the first report of a Taiwanese strain of an OXA-66/OXA-51-like carbapenemase that confers imipenem resistance in A. baumannii.

In this study, 830 Streptococcus pyogenes isolates collected between 2001 and 2002 from patients with scarlet fever in northern Taiwan were analyzed by M protein gene (emm) sequence typing, pulsed-field gel electrophoresis (PFGE), and antimicrobial susceptibility testing. A total of 21 emm types and 56 PFGE patterns were identified. The most frequent emm types were emm1 (29.2%), emm4 (24.1%), emm12 (19.0%), emm6 (15.8%), stIL103 (5.7%), and emm22 (1.9%). Antimicrobial resistance profiles were determined, and resistance to erythromycin (24.6%), clindamycin (2.0%), and chloramphenicol (1.3%) was detected. Five major emm types (emm4, emm12, emm1, emm22, and emm6) accounted for 95.6% of the erythromycin-resistant isolates. The decreased prevalence of erythromycin-resistant emm12 strains coincided with the overall decrease in erythromycin resistance from 32.1% in 2001 to 21.1% in 2002 in Taiwan. Five major clones (emm4/2000, emm12/0000, emm4/2010, emm1/1000, and emm22/8100) represented 72.1% of the erythromycin-resistant isolates. The survey of group A Streptococcus emm types, genetic diversity, and antibiotic resistance has direct relevance to current antimicrobial use policies and potential vaccine development strategies.

In Taiwan, routine pertussis immunization has been implemented for more than 40 years and a low incidence of pertussis was maintained until an 80-fold increase in cases occurred in 1992. The unexpected increase emphasized the significance of pertussis. This study evaluated a total of 2452 reported cases of pertussis during 1993-2004 and surveillance data on incidence, age distribution and seasonality. The highest morbidity was in infants aged <1 year, and upward trends in the incidence of pertussis were significant for infants aged <1 year and adolescents aged 10-14 years. The highest mean number of cases was observed in August and upward trends were in colder months. This study indicates that the epidemiology of pertussis may have been changed by waning immunity in Taiwan. Increased surveillance activities, especially in older age groups, and additional booster doses of acellular pertussis vaccine for children aged 6-8 years and adolescents/young adults aged 15-20 years are necessary to control and prevent pertussis.

Background: Previous studies suggest that the serotonin-3 (5-HT3) receptor antagonist ondansetron possesses the therapeutic potential for schizophrenia. This study was designed to determine whether ondansetron as an adjunct to haloperidol could enhance the clinical efficacy and reduce the adverse side effects in chronic treatment-resistant schizophrenia., Methods: Under double-blind, randomized conditions, 121 treatment-resistant inpatients with chronic DSM-IV-diagnosed schizophrenia received haloperidol (4-30 mg/day) combined with either placebo (N=63) or a fixed dose of 8 mg/day of ondansetron (N=58) for 12 weeks. Efficacy was defined as the change from baseline to endpoint in score on overall scale and subscales of the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity (CGI-S). Side effects were evaluated using the Treatment Emergent Symptom Scale and Extrapyramidal Symptom Rating Scale., Results: Ondansetron combined with haloperidol produced a significantly greater improvement on PANSS overall scale and subscales for negative symptoms, general psychopathology, and cognition at endpoint compared to placebo with haloperidol, but no between-treatment group difference was observed on the subscale for positive symptoms and CGI-S. The ondansetron-treated group had a significantly higher proportion of patients with a 30% or greater baseline-to-endpoint reduction in PANSS total score than placebo. Patients in adjunctive ondansetron therapy also experienced significantly lower incidence and severity of parkinsonism and akathisia as well as fewer behavioral hyperactivity, cardiac, and gastrointestinal side effects., Conclusions: Ondansetron is an effective adjunctive agent in enhancing the effectiveness and reducing some adverse side effects of antipsychotic therapy for chronic, treatment-resistant schizophrenia, particularly for negative and cognitive symptoms.

A total of 522 Streptococcus pneumoniae invasive isolates from diverse sources were collected from January 2002 to December 2003 in Taiwan in order to understand the serotype distribution of invasive isolates in Taiwan. The most frequently isolated serotypes of S. pneumoniae were types 14 (18.4%), 23F (15.1%), 3 (13.8%), 19F (13.4%), 6B (8.2%), 9V (3.6%) and 4 (2.5%). The majority of cases were either under 5 years of age (24.1%) or older than 65 years (36.6%). Serotype distribution in adults aged over 14 years and children aged under 2 years was similar, except for that of type 3, which was more prevalent in adults. Penicillin-non-susceptible strains accounted for 67.7% of all strains and were the predominant strains of serotypes 23F, 19F, 6B and 14. Most strains were susceptible to cephem drug, 85.7% of isolates were susceptible to cefotaxime and 92.9% were susceptible to ceftriaxone. A total of 72.6% (379/522) of the isolates were resistant to at least two antibiotics. The 23-valent vaccine in the current commercial market would cover 87.2% of the serotypes and 100% of the penicillin-non-susceptible serotypes of S. pneumoniae in Taiwan. The coverage of 7- and 11-valent protein conjugate vaccines of the serotypes in children under 2 years of age would be 78.8 and 86.5%, respectively. These results will help to assess the adequacy of the vaccine formulations marketed in Taiwan.

Pertussis reemerges periodically despite high pertussis vaccination coverage in many countries. We used prn and fim3 gene sequences and pulsed-field gel electrophoresis (PFGE) to analyze the molecular epidemiology of 168 clinical isolates of Bordetella pertussis during 1993-2004, and deduced possible reasons for an outbreak in 1997 in Taiwan. In Taiwan, during 1996-1997, a shift of prn1 to prn2 was reflected in a transition of PFGE group I to group IIIa; during 2000-2001, the change from fim3A to fim3B was displayed in transition of PFGE group IIIa to group IIIb. These changes were also consistent with the two peaks of pertussis incidence in 1997 and 2000. In 1997, a larger than expected increase in the incidence of pertussis occurred and isolates were characterized by complicated pulsotypes, appearance of many new profiles and an unusual presence of prn3. Based on a high resemblance of PFGE profiles and the same virulence genes, a similar shift of circulating strains was observed in European countries as well as Taiwan; thus, the high incidence of pertussis in 1997 may be due to an international expansion of B. pertussis strains from a similar source. This study provides further elucidation of the global molecular epidemiology of B. pertussis.

Background: Meningococcal disease is infrequently found in Taiwan, a country with 23 million people. Between 1996 and 2002, 17 to 81 clinical cases of the disease were reported annually. Reported cases dramatically increased in 2001-2002. Our record shows that only serogroup B and W135 meningococci have been isolated from patients with meningococcal disease until 2000. However, serogroup A, C and Y meningococci were detected for the first time in 2001 and continued to cause disease through 2002. Most of serogroup Y meningococcus infections localized in Central Taiwan in 2001, indicating that a small-scale outbreak of meningococcal disease had occurred. The occurrence of a meningococcal disease outbreak and the emergence of new meningococcal strains are of public health concern., Methods: Neisseria meningitidis isolates from patients with meningococcal disease from 1996 to 2002 were collected and characterized by serogrouping, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). The genetic relatedness and clonal relationship between the isolates were analyzed by using the PFGE patterns and the allelic profiles of the sequence types (STs)., Results: Serogroups A, B, C, W135, Y, and non-serogroupable Neisseria meningitidis were, respectively, responsible for 2%, 50%, 2%, 35%, 9%, and 2% of 158 culture-confirmed cases of meningococcal disease in 1996-2002. Among 100 N. meningitidis isolates available for PFGE and MLST analyses, 51 different PFGE patterns and 30 STs were identified with discriminatory indices of 0.95 and 0.87, respectively. Of the 30 STs, 21 were newly identified and of which 19 were found in serogroup B isolates. A total of 40 PFGE patterns were identified in 52 serogroup B isolates with the patterns distributed over several distinct clusters. In contrast, the isolates within each of the serogroups A, C, W135, and Y shared high levels of PFGE pattern similarity. Analysis of the allelic profile of the 30 STs suggested the serogroup B isolates be assigned into 5 clonally related groups/ clonal complexes and 7 unique clones. The ST-41/44 complex/Lineage 3, and the ST-3439 and ST-3200 groups represented 79% of the serogroup B meningococci. In contrast, isolates within serogroups A, serogroup W135 (and C), and serogroup Y, respectively, simply belonged to ST-7, ST-11, and ST-23 clones., Conclusion: Our data suggested that serogroup B isolates were derived from several distinct lineages, most of which could either be indigenous or were introduced into Taiwan a long time ago. The serogroup A, W135 (and C), and Y isolates, respectively, belonged to the ST-7, ST-11, and ST-23, and the represented clones that are currently the major circulating clones in the world and are introduced into Taiwan more recently. The emergence of serogroup A, C and Y strains contributed partly to the increase in cases of meningococcal disease in 2001-2002.