Comparison of ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and enzyme-multiplied immunoassay technique (EMIT) for quantification of voriconazole plasma concentration from Chinese patients.

Introduction: Voriconazole (VRZ) is the recommended standard treatment for life-threatening invasive aspergillosis. The plasma concentration of VRZ should be determined to optimise treatment results and reduce side effects. This study aimed to compare the correlation and concordance of ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and enzyme-multiplied immunoassay technique (EMIT) to determine VRZ plasma concentration in clinical practice. Methods: An isotopically labelled internal standard UPLC-MS/MS method was established, validated, and subsequently applied to determine VRZ concentration. The UPLC-MS/MS method was also compared with a commercial EMIT method regarding results correlation and concordance. Results: The calibration curve of UPLC-MS/MS was linear from 0.1 to 10 mg/L, the inter- and intra-day relative standard deviations (RSDs), and the stability of quality control samples were less than 15 %, satisfying the Bioanalytical Method Validation Guidelines. A total of 122 plasma samples were collected and analyzed using both methods. UPLC-MS/MS and EMIT showed a high correlation (r = 0.9534), and Bland-Altman analysis indicated a mean absolute bias of 1.035 mg/L and an average bias of 27.56 % between UPLC-MS/MS and EMIT. The paired Wilcoxon test and Bland-Altman analysis revealed poor consistency between the two methods. Furthermore, we compared the effects of different methods in clinical applications. Two threshold values for treatment efficacy (1.0 mg/L) and safety (5.5 mg/L) were established, and considerable discordance was observed between the original EMIT and UPLC-MS/MS results at both thresholds (p < 0.05). Nevertheless, the adjusted EMIT results were not inconsistent with the UPLC-MS/MS results regarding the efficacy (p = 0.125) and safety (p = 1.0) thresholds. Conclusions: The isotopically labelled internal standard UPLC-MS/MS method is established and well applied in the clinical setting. A strong correlation but discordance was found between UPLC-MS/MS and EMIT, indicating that switching from UPLC-MS/MS to EMIT was unsuitable. However, the adjusted EMIT results may serve as a reliable surrogate when UPLC-MS/MS results cannot be obtained when necessary.

High risks adverse events associated with trastuzumab emtansine and trastuzumab deruxtecan for the treatment of HER2-positive/mutated malignancies: a pharmacovigilance study based on the FAERS database.

BACKGROUND: T-DM1 and T-DXd are two promising antibody-drug conjugates for treating advanced HER2-positive breast cancer and HER2-mutated lung cancer. Understanding the differences in the adverse events (AEs) profile of both drugs may help clinicians make an appropriate treatment decision. RESEARCH DESIGN AND METHODS: All data obtained from the FDA Adverse Event Reporting System (FAERS) database from Q1 2004 to Q3 2022 underwent disproportionality analysis and Bayesian analysis to detect and assess the AE signals of T-DM1 and T-DXd for comparison. RESULTS: A total of 2,113 and 1,269 AE reports associated with T-DM1 and T-Dxd, respectively, were retrieved from FAERS database, in which, respondents were mostly elderly women. Their statistical differences (p < 0.001), poses high incidence of thrombocytopenia, including cardiotoxicity (p < 0.05) for T-DM1, while myelosuppression, interstitial lung disease (ILD), and pneumonitis for T-DXd. Splenomegaly, nodular regenerative hyperplasia, hepatic cirrhosis, portal hypertension, neuropathy peripheral, and spider nevus, are particular to T-DM1. Similarly, febrile neutropenia, pneumocystis jirovecii pneumonia, neutrophil count decreased, and KL-6 increased, are unique to T-DXd. CONCLUSIONS: T-DXd is more likely to induce ILD/pneumonia and myelosuppression than T-DM1, whereas T-DM1 has higher risk of hepatotoxicity, cardiotoxicity, and thrombocytopenia than T-DXd. T-DM1-related hepatotoxicity may need redefinition. Clinicians may need to balance the benefits and risks of antibody-drug conjugates treatment for certain patients.

Pharmacokinetic/pharmacodynamic comparison between generic and brand-name levofloxacin based on Monte Carlo simulation.

OBJECTIVE: Generic medications are widely used because of their low cost. However, some generic medications show lower quality and clinical efficacy compared with brand-name medications, especially for antimicrobial drugs. Levofloxacin is a fluoroquinolone antimicrobial drug with excellent antimicrobial activity and wide antimicrobial spectrum, while it is susceptible to drug resistance. Our study aims to evaluate the bioequivalence of generic and brand-name levofloxacin. METHODS: The pharmacokinetic (PK) parameters (Cmax, AUC0∼24, Tmax, and t1/2), pharmacodynamic (PD) parameters (in vitro antibacterial activity and the inhibition of resistant mutation), and PK/PD analysis (the probability of target attainment; the cumulative fraction of response) calculated by Monte Carlo simulation were investigated. RESULTS: Our results demonstrated that compared with generics, brand-name levofloxacin not only had higher drug content, it also showed higher antimicrobial susceptibility, higher resistance to mutation ability, and higher percentage of each dosage interval wherein plasma concentration of antimicrobial agents exceeded the MPC90 (mutant prevention concentration to prevent the mutation of 90% strains) against various clinical isolates. Although the differences in AUC0∼24 between brand-name levofloxacin and generics were not statistically significant (P > 0.05, F test), Monte Carlo simulation results showed cumulative fraction of response values for PK/PD of brand-name medications were higher than generics. CONCLUSION: Our results indicated that PK or PD equivalence did not imply therapeutic equivalence; thus, we suggest including PK/PD analysis in the bioequivalence evaluation system, which benefits prediction of clinical outcome with high application value.

FDI and Wellbeing: A Key Node Analysis for Psychological Health in Response to COVID-19 Using Artificial Intelligence.

Developing countries are primary destinations for FDI from emerging economies following the World Investment Report 2022, including destinations in OECD countries. Based on three theoretical lenses and case analyses, we argue that Chinese outward FDI has impacts on wellbeing in destination countries, and that this is an important issue for psychological health in response to COVID-19. Based on the super-efficiency DEA approach, our study investigated the impact of Chinese outward FDI on wellbeing in OECD countries. We also applied a Tabu search to identify country groups based on the relationship between Chinese outward FDI and wellbeing and we developed a key node analysis of the country groups using an immune algorithm. This research has implications for public administrators in global governance and could help shape FDI policies to improve psychological health of the destination countries in response to COVID-19.

Chinese consensus guidelines for therapeutic drug monitoring of polymyxin B, endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. / å¤šé»èŒç´ Bæ²»ç–—è¯ç‰©ç›‘æµ‹ä¸“å®¶å ±è¯†ï¼šä¸­å›½è¯ç†å­¦ä¼šæ²»ç–—è¯ç‰©ç›‘æµ‹ç ”ç©¶ä¸“ä¸šå§”å‘˜ä¼šåŠä¸Šæµ·å¸‚åŒ»å­¦ä¼šæ„ŸæŸ“ä¸ŽåŒ–ç–—ä¸“ç§‘åˆ†ä¼šå‘èµ·åˆ¶å®š.

Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.

Ocular adverse events associated with anti-VEGF therapy: A pharmacovigilance study of the FDA adverse event reporting system (FAERS).

Background: The purpose of this study is to identify and characterize ocular adverse events (AEs) that are significantly associated with anti-VEGF drugs for treatment of neovascular age-related macular degeneration and compare the differences between each drug, and provide clinical reference. Methods: Ocular AEs submitted to the US Food and Drug Administration were analyzed to map the safety profile of anti-VEGF drugs. The Pharmacovigilance tools used for the quantitative detection of signals were reporting odds ratio and bayesian confidence propagation neural network. Results: A total of 10,608,503 AE reports were retrieved from FAERS, with 20,836 for ranibizumab, 19,107 for aflibercept, and 2,442 for brolucizumab between the reporting period of Q1, 2004 and Q3, 2021. We found and analyzed the different AEs with the strongest signal in each drug-ranibizumab-macular ischaemia (ROR = 205.27, IC-2SD = 3.70), retinal pigment epithelial tear (ROR = 836.54, IC-2SD = 7.19); aflibercept-intraocular pressure increased (ROR = 31.09, IC-2SD = 4.61), endophthalmitis (ROR = 178.27, IC-2SD = 6.70); brolucizumab-retinal vasculitis (ROR = 2930.41, IC-2SD = 7.47) and/or retinal artery occlusion (ROR = 391.11, IC-2SD = 6.10), dry eye (ROR = 12.48, IC-2SD = 2.88). Conclusion: The presence of AEs should bring clinical attention. The use of anti-VEGF drugs should be based on the patient's underlying or present medical condition to reduce any adverse event associated with the treatment.

Variation in Sediment Available-Phosphorus in Dianchi Lake and Its Impacts on Algal Growth.

Sediment phosphorus (P) is an active component of the P cycle in lakes and its availability and movement could play an important role in eutrophication. Sediments from different depths in five representative sites of Dianchi Lake China, i.e., Haigeng, Dounan, Luojiacun, Xinjie, and Kunyang, were studied from January to December to evaluate the spatial and temporal dynamics in available-P and soluble-P and their impacts on algal growth. The results showed that the average sediment available-P and soluble-P were 41.2 mg kg-1 and 0.27 mg kg-1, respectively. Sediment available-P and soluble-P concentrations varied significantly among seasons, sites, and layers, with the following order: surface (0-5 cm) > middle (5-10 cm) > bottom (10-20 cm). The release and transformation characteristics of available-P and soluble-P at the sediment-water interface varied among sites. The Haigeng site, with the most severe algae blooms, had significantly higher average available-P and soluble-P in sediment than other sites. This indicated that phosphorus release and availability were associated with algal growth, and that the sediment surface (0-5 cm) is an important internal source that supports algal growth in Dianchi Lake.

Guideline for the management of pediatric off-label use of drugs in China (2021).

BACKGROUND: The "Law on Doctors of the People's Republic of China," which was officially implemented on March 1, 2022, emphasizes the requirements for rational drug use and the necessity for appropriate management of off-label drug use. The safety and ethical considerations related to off-label drug use are different in children than in adults. There is so far no management guideline for pediatric off-label use of drugs in China, and the applicability of foreign guidelines is limited. Establishing a localized evidence-based management guideline for pediatric off-label use of drugs to support the national legislation and clinical practice is of critical importance. METHODS: We established a guideline working group, including experts from a broad range of disciplines and developed recommendations following the guidance of the World Health Organization Handbook and the Chinese Medical Association. The following themes were identified by questionnaires and expert interviews to be of great concern in the management of off-label drug use in children: general principles and characteristics of management of pediatric off-label drug use; establishment of expert committees; evidence evaluation; risk-benefit assessment; informed consent; monitoring and assessment of the risk; and monitoring and patient education. Two rounds of Delphi surveys were organized to determine the final recommendations of this guideline. We graded the recommendations based on the body of evidence, referring to the evaluation tool of the Evidence-based management (EBMgt) and the Oxford Center for Evidence-Based Medicine: Level of Evidence (March 2009). RESULTS: We developed the first guideline for the management of pediatric off-label use of drugs in China. CONCLUSIONS: The guideline is to offer guidance for pediatricians, pharmacists, medical managers, policymakers, and primary care physicians on how to manage off-label drug use in pediatrics and to provide recommendations for Chinese healthcare policy in the future.

The Mobile Phone Addiction and Depression Among High School Students: The Roles of Cyberbullying Victimization, Perpetration, and Gender.

Objective: To examine the relation between mobile phone addiction and high school students' depression, and its inner mechanism-the sequential mediating roles of the cyberbullying victimization and the cyberbullying perpetration in this relationship. Methods: 1297 high school students were recruited to complete the Smartphone Addiction Scale, European Cyberbullying Intervention Project Questionnaire and the Center for Epidemiological Studies Depression Scale. Results: (1) Mobile phone addiction was positively correlated with and high school students' depression; (2) cyberbullying victimization and the cyberbullying perpetration significantly mediated the relation between mobile phone addiction and high school students' depression, which contained tow mediating paths-the independent mediating effects of cyberbullying victimization and the sequential mediating effect of cyberbullying victimization and the cyberbullying perpetration; (3) there are gender differences in the sequential mediation model, and boys who are victims of cyberbullying are more likely to develop into cyberbullying perpetrators than girls. Conclusion: The results of this study indicate that depression among high school students with mobile phone addiction can be eliminated through the development of cyberbullying victimization and the cyberbullying perpetration.

Construction and Interpretation of Prediction Model of Teicoplanin Trough Concentration via Machine Learning.

Objective: To establish an optimal model to predict the teicoplanin trough concentrations by machine learning, and explain the feature importance in the prediction model using the SHapley Additive exPlanation (SHAP) method. Methods: A retrospective study was performed on 279 therapeutic drug monitoring (TDM) measurements obtained from 192 patients who were treated with teicoplanin intravenously at the First Affiliated Hospital of Army Medical University from November 2017 to July 2021. This study included 27 variables, and the teicoplanin trough concentrations were considered as the target variable. The whole dataset was divided into a training group and testing group at the ratio of 8:2, and predictive performance was compared among six different algorithms. Algorithms with higher model performance (top 3) were selected to establish the ensemble prediction model and SHAP was employed to interpret the model. Results: Three algorithms (SVR, GBRT, and RF) with high R 2 scores (0.676, 0.670, and 0.656, respectively) were selected to construct the ensemble model at the ratio of 6:3:1. The model with R 2 = 0.720, MAE = 3.628, MSE = 22.571, absolute accuracy of 83.93%, and relative accuracy of 60.71% was obtained, which performed better in model fitting and had better prediction accuracy than any single algorithm. The feature importance and direction of each variable were visually demonstrated by SHAP values, in which teicoplanin administration and renal function were the most important factors. Conclusion: We firstly adopted a machine learning approach to predict the teicoplanin trough concentration, and interpreted the prediction model by the SHAP method, which is of great significance and value for the clinical medication guidance.

Effect of CYP2C19 polymorphism on the plasma voriconazole concentration and voriconazole-to-voriconazole-N-oxide concentration ratio in elderly patients.

BACKGROUND: Effects of CYP2C19 polymorphism on voriconazole concentration (C0 ), dose-adjusted trough concentrations (C0 /dose) and voriconazole-to-voriconazole-N-oxide concentration ratio (C0 /CN ) have not been fully investigated. OBJECTIVES: To investigate correlations of CYP2C19 polymorphisms with plasma concentrations of voriconazole and the major metabolite voriconazole-N-oxide in elderly patients. METHODS: A prospective, multi-centre, non-intervention, open clinical study was conducted within Southwestern Chinese patients clinically diagnosed with invasive fungal infections, to investigate the associations of CYP2C19∗2 (681G > A), CYP2C19∗3 (636G > A) and CYP2C19∗17 (-806C > T) genetic polymorphisms with voriconazole C0 , C0 /dose and C0 /CN . RESULTS: The study included 131 adult patients, of which 72 were elderly (≥60 years) and 59 were adults (<60 years). The allele frequencies of CYP2C19∗2, ∗3 and ∗17 in the elderly cohort were 61.1%, 29.9% and 7.6%, respectively, which were similar to those in the adult cohort (66.9%, 29.7% and 2.5%, respectively; P > .05). The median voriconazole C0 (C0 ), C0 /dose and C0 /CN ratio in patients with the CYP2C19∗1/∗2 and CYP2C19∗2/∗2 genotypes were significantly higher than those in patients with the CYP2C19∗1/∗1 genotype in the adult cohort (P < .05). The C0 and C0 /dose in patients with the CYP2C19∗1/∗3 and CYP2C19∗2/∗2 genotypes, and the C0 /CN ratio for patients with the CYP2C19∗1/∗2 genotype were numerically higher than those in patients with the CYP2C19∗1/∗1 genotype in the elderly cohort, but this difference was not statistically significant (P > 0.05). The C0 , C0 /dose and C0 /CN in patients with poor metaboliser phenotypes were higher than in those with normal metaboliser phenotypes and C0 in patients with intermediate metaboliser phenotypes were significantly higher than in those with normal metaboliser phenotypes in the adult cohort (P < .05). However, there were no significant differences in the C0 , C0 /dose and C0 /CN among different CYP2C19-predicted metabolic phenotypes in the elderly cohort. CONCLUSIONS: Voriconazole C0 , C0 /dose and C0 /CN ratio are not significantly affected by the CYP2C19∗2/∗3 polymorphisms in the elderly patients.

Experiences of parents providing kangaroo care to a premature infant: A qualitative systematic review.

Parents who give birth to an unexpected preterm infant not only suffer a psychological impact, but, in addition, their roles as parent are full of uncertainty. As part of family-centered care, kangaroo care is an important way to support premature infants and their family. This review synthesizes qualitative studies on the experiences of parents who have used kangaroo care for preterm infants in neonatal intensive care units. English and Chinese databases were searched for relevant studies from 1970 to July 2018. The findings of qualitative studies were extracted and pooled using the Joanna Briggs Institute Qualitative Assessment and Review Instrument. A total of 731 studies were screened, and 9 were included. Five synthesized findings were identified: sense of emptiness of the parent's role, barriers in the translation of parental roles in kangaroo care, preparation enhances parental role expectations, kangaroo care enhances parental competency, and encouragement and support from family and friends. Through the implementation of kangaroo care, nurses are able to help prepare and guide parents, fit parents' needs, and help improve their ability and self-confidence in their parental roles.

Child-rearing experiences and home environment concerns among Southeast Asian immigrant mothers in transnational marriage families in Taiwan.

AIMS: To explore the child-rearing experiences of immigrant mothers and their concerns about children's home environments in the contexts of transnational marriage families and non-native culture. BACKGROUND: Immigrant mothers are often disadvantaged by a relative lack of information on and access to children's healthcare, but little research exists on the experiences of mothers in transnational marriage families as they attempt to provide a secure home environment while navigate an unfamiliar culture. DESIGN: A descriptive phenomenological research design based on intuition was employed to explore immigrant mothers' unique lived reality through their subjective experiences and perceptions. METHODS: Semi-structured interviews with 15 immigrant mothers from 15 transnational marriage families were conducted between May 2016-February 2017. Narratives were analyzed using the descriptive phenomenological method because it permits systematic discovery of the lived experiences from the perspective of the study's participants. RESULTS: Three major themes were identified: (a) striving to maintain a secure home for children; (b) suffering and struggling with difficulties; and (c) trying to overcome difficulties and build an adequate family environment. The essential, prevailing concept of immigrant mothers' experience in child-rearing was identified as 'Where my child is, is home.' CONCLUSION: Immigrant mothers bond emotionally and physically to their new land via their children. Their child-raising experiences are interwoven with their roles in their new familial and cultural homes. IMPACT: Immigrant brides often become mothers soon after marrying to continue their husbands' family line. Understanding their unique child-rearing experiences and challenges in providing a secure home in a non-native culture will help nurses provide effective care. Study results will benefit paediatric/family nurses in any setting where care for transnational marriage families is provided, those families themselves, public policymakers and future researchers.

Evaluation of nursing students' perceptions of their cultural care competency: A mixed method study in Taiwan.

Growing cultural diversity among immigrants has challenged health care practice in Taiwan. This study used mixed methods to evaluate how the implementation of a course on cultural competence embedded in a nursing course affected nursing students' perceptions of their cultural care competency. An evaluation survey with a quantitative questionnaire comprising pre- and post-test measures of self-perceived cultural care competency was implemented for 48 participants at the commencement and completion of the course. A focus group interview (n = 10) was conducted and a thematic approach applied to analyze qualitative data. The results found a significant improvement in self-perceived cultural care competency (t = 7.15, p < 0.001). Two themes emerged from the qualitative analysis: (1) the thought-provoking nature of the course and (2) appreciation for the multiple learning strategies of the course. The findings suggest that embedding cultural competence education in nursing courses is essential to improving nursing students' perceptions of their cultural care competency.

Antimicrobial resistance surveillance and prediction of Gram-negative bacteria based on antimicrobial consumption in a hospital setting: A 15-year retrospective study.

Antimicrobial resistance, a major threat to human health, is mainly driven by the overuse of antimicrobials. The purpose of this study was to further investigate the relationship between antimicrobial use and resistance with a 15-year record in Southwest hospital, one of the largest hospitals in Southwest China and a university affiliated hospital, thus to further predict the antimicrobial resistance in an autoregressive integrated moving average (ARIMA) manner. Kirby-Bauer tests were carried out to figure out the drug sensitivity of Gram-negative bacterial. Antimicrobials (ß-lactamase inhibitor complex, aminoglycosides, quinolones, third and fourth-generation cephalosporins, carbapenems, cephamycins, oxacephems, and sulfonamides) consumption were calculated according to World Health Organization (WHO) anatomical therapeutic chemical classification index and expressed as annual defined daily dose (DDD) or DDD per 1000 out patients. Resistance rates of levofloxacin-resistant Escherichia coli, ceftazidime-resistant Klebsiella pneumoniae, amikacin-resistant Bacterium levans, imipenem-resistant Pseudomonas aeruginosa is positively correlated with the usage of aminoglycosides and quinolones; resistance rates of imipenem-resistant Acinetobacter baumanii is positively correlated with the usage of carbapenemes (P-value between the drug resistance of levofloxacin-resistant E. coli, ceftazidime-resistant K. pneumoniae and the usage of aminoglycosides is under .05, the other P-value are under .01); resistance rates of the drug resistance of levofloxacin-resistant E. coli is positively correlated with the usage of oxacephems (P < .01); resistance rates of imipenem-resistant P. aeruginosa is positively correlated with the usage of oxacephems and sulfonamides (P < .01).The present study presents one of the largest and longest retrospective analyses in China between antimicrobial consumption and antimicrobial resistance. Change of the usage of several antibacterial drugs has great influence on the drug resistance of Gram-negative bacterial. Of particular, ARIMA forecasting revealed that carbapenem related bacterial resistance should be closely watched.

Revision and validation of a short scale to assess home environment for elementary school children in transnational families in Taiwan.

PURPOSE: To develop and test a brief scale of the home environment of elementary school children in transnational families or vulnerable families. DESIGN AND METHODS: The scale development process took place in three phases. In the first phase, a 61-item scale was generated by an expert panel based upon related literature and Chinese Home Observation for Measurement of the Environment (C-HOME). In the second phase 15 individual transnational families with elementary school children were interviewed, and items were reduced from 61 to 55 due to understandability or other practical considerations. Phase three's item analysis with 200 such families, reduced items to 41. Factor analysis followed, further reducing items to 27. Finally, the resulting 27-item scale underwent a test-retest with 57 subsample participants. RESULTS: An iterative process of item and factor analyses identified a seven-dimensional, 27-item Home Environment Assessment Scale (HEAS), which accounted for 52.28% of the total variance. K-R 20 was 0.76. The test-retest reliability for the full sample total score was 0.97. CONCLUSIONS: The results provide evidence supporting the scale consistency, content validity, and construct validity, and offer a useful instrument for health care professionals, especially pediatric nurses, to identify home environment interventions for young children in vulnerable families. PRACTICE IMPLICATIONS: The findings of HEAS-27 can serve to guide pediatric health care professionals in promptly screening, evaluating, and teaching families so that children in a vulnerable population have adequate quality and quantity of support in the home environment.

Macrophage ABHD5 Suppresses NFκB-Dependent Matrix Metalloproteinase Expression and Cancer Metastasis.

Metabolic reprogramming in tumor-associated macrophages (TAM) is associated with cancer development, however, the role of macrophage triglyceride metabolism in cancer metastasis is unclear. Here, we showed that TAMs exhibited heterogeneous expression of abhydrolase domain containing 5 (ABHD5), an activator of triglyceride hydrolysis, with migratory TAMs expressing lower levels of ABHD5 compared with the nonmigratory TAMs. ABHD5 expression in macrophages inhibited cancer cell migration in vitro in xenograft models and in genetic cancer models. The effects of macrophage ABHD5 on cancer cell migration were dissociated from its metabolic function as neither triglycerides nor ABHD5-regulated metabolites from macrophages affected cancer cell migration. Instead, ABHD5 deficiency in migrating macrophages promoted NFκB p65-dependent production of matrix metalloproteinases (MMP). ABHD5 expression negatively correlated with MMP expression in TAMs and was associated with better survival in patients with colorectal cancer. Taken together, our findings show that macrophage ABHD5 suppresses NFκB-dependent MMP production and cancer metastasis and may serve as a prognostic marker in colorectal cancer. SIGNIFICANCE: These findings highlight the mechanism by which reduced expression of the metabolic enzyme ABHD5 in macrophages promotes cancer metastasis.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/21/5513/F1.large.jpg.

Antimicrobial Activity of Galangin and Its Effects on Murein Hydrolases of Vancomycin-Intermediate Staphylococcus aureus (VISA) Strain Mu50.

Backgroud: Antibiotic treatment for infections caused by vancomycin-intermediate Staphylococcus aureus (VISA) strains is challenging, and only a few effective and curative methods have been developed to combat these strains. This study aimed to investigate the antimicrobial activity of galangin against S. aureus and its effects on the murein hydrolases of VISA strain Mu50. This is the first report on these effects of galangin, and it may help to improve the treatment for VISA infections by demonstrating the effective use of galangin. METHODS: Firstly, the minimum inhibitory concentration (MIC) and growth curve were used to investigate the antimicrobial activity of galangin against S. aureus. Secondly, transmission electron microscopy (TEM) was used to observe morphological changes of VISA strain Mu50. Thirdly, Triton X-100-induced autolysis and cell wall hydrolysis assays were performed to determine the activities of the murein hydrolases of Mu50. Finally, fluorescence real-time quantitative PCR was used to investigate the expression of the murein hydrolase-related Mu50 genes. RESULTS: The results indicated that the MIC of galangin was 32 µg/mL against ATCC25293, N315, and Mu50, and galangin could significantly suppress the bacterial growth (p < 0.05) with concentrations of 4, 8 and 16 µg/mL, compared with control group (0 µg/mL). To explore the possible reasons of bacteriostatic effects of galangin, we observed morphological changes using TEM which showed that the division of Mu50 daughter cells treated with galangin was obviously inhibited. Considering the vital role of murein hydrolases in cellular division, assays were performed, and galangin markedly decreased Triton X-100-induced autolysis and cell wall hydrolysis. Galangin also significantly inhibited the expression of the murein hydrolase genes (atl, lytM, and lytN) and their regulatory genes (cidR, cidA, and cidB). CONCLUSIONS: Our findings indicated that galangin can effectively inhibit murein hydrolase activity as well as the growth of VISA strain Mu50.

Hyperoside inhibits biofilm formation of Pseudomonas aeruginosa.

Pseudomonas aeruginosa (P. aeruginosa) is a common pathogen in hospital-acquired infection and is readily able to form biofilms. Due to its high antibiotic resistance, traditional antibacterial treatments exert a limited effect on P. aeruginosa biofilm infections. It has been indicated that hyperoside inhibits P. aeruginosa PAO1 (PAO1) biofilm formation without affecting growth. Therefore, the current study examined the biofilm formation and quorum sensing (QS) system of PAO1 in the presence of hyperoside. Confocal laser scanning microscopy analysis demonstrated that hyperoside significantly inhibited biofilm formation. It was also observed that hyperoside inhibited twitching motility in addition to adhesion. Data from reverse transcription-quantitative polymerase chain reaction indicated that hyperoside inhibited the expression of lasR, lasI, rhlR and rhlI genes. These results suggest that the QS-inhibiting effect of hyperoside may lead to a reduction in biofilm formation. However, the precise mechanism of hyperoside on P. aeruginosa pathogenicity remains unclear and requires elucidation in additional studies.

Reduced nosocomial infection rate in a neonatal intensive care unit during a 4-year surveillance period.

BACKGROUND: Hospital-acquired infections are a leading cause of morbidity and mortality in neonatal intensive care units (NICU). The aim of the study was to investigate the change of nosocomial infection rate in a NICU during a 4-year surveillance period. METHODS: We investigated the changes in nosocomial infection rates, infection sites, and microorganism species in a NICU before and after the unit was moved to a new location, extending from November 2008 to October 2012.The new facility was opened on November 1, 2010 and the old NICU was closed on the same day. In the meantime, three catheter-based bundles were implemented in the new NICU and all intensive care units in our hospital due to the new policy. Data collection was performed by independent, experienced infection control nurses. RESULTS: A total of 512 neonates were admitted to the NICU and enrolled in this study. There were 242 infants who were admitted to the old NICU, and 270 infants in the new facility. During the study period, the rate of infection episodes decreased from 19.0% to 11.1% (P = 0.01). Additionally, the average hospital-acquired infection rate decreased from 6.26 cases per 1000 patient-days to 4.09 cases per 1000 patient-days (P = 0.03). The most common infection site was blood stream infection, which decreased from 8.3% to 3.7% (P = 0.03). The total catheter-related infection rates of the blood stream, lower respiratory tract, and urinary tract decreased from 13.6% to 5.9% (P = 0.003). Klebsiella pneumonia, E. coli, Methicillin-resistant Staphylococcus aureus (MRSA), and Coagulase-negative Staphylococci (CoNS) were the most frequently found pathogens in the old NICU, whereas MRSA, CoNS, E. faecalis, and A. baumannii were the most frequently found pathogens in the new NICU. CONCLUSION: The change in the environment and implementation of device bundles in the NICU might be associated with the nosocomial infection rate.