The response of CD27+CD38+ plasmablasts, CD24hiCD38hi transitional B cells, CXCR5-ICOS+PD-1+ Tph, Tph2 and Tfh2 subtypes to allergens in children with allergic asthma.

BACKGROUND: Allergic asthma is a type I allergic reaction mediated by serum Immunoglobulin E (IgE). B cell-mediated humoral immune response to allergens in the pathophysiology of allergic asthma have not been thoroughly elucidated. Peripheral helper T cells (Tph) and follicular helper T cells (Tfh) promote B cell differentiation and antibody production in inflamed tissues. OBJECTIVE: To investigate the roles of B cell subsets, Tph cell subsets and Tfh cell subsets in allergic immune responses. METHODS: Circulating B cell subsets, Tph cell subsets and Tfh cell subsets in 33 children with allergic asthma and 17 healthy children were analyzed using multicolor flow cytometry. The level of serum total IgE was also assessed. RESULTS: Our study found that CD27+CD38+ plasmablasts and CD24hiCD38hi transitional B cells increased and were correlated with serum total IgE level, CD27- naive B cells and CD24hiCD27+ B cells decreased in children with allergic asthma. CXCR5- Tph, CXCR5-ICOS+ Tph, CXCR5-ICOS+PD-1+ Tph, CXCR5+ICOS+ Tfh and CXCR5+ICOS+PD-1+ Tfh increased in children with allergic asthma. Further analysis showed increased Tph2, Tph17, Tfh2 and Tfh17 subtypes while decreased Tph1 and Tfh1 subtypes in children with allergic asthma. Most interestingly, Tph2 or Tfh2 subtypes had a positive correlation with serum total IgE level. CONCLUSION: Overall, these results provide insight into the allergens elicited B, Tph or Tfh cell response and identify heretofore unappreciated CD24hiCD38hi transitional B cells, CD24hiCD27+ B cells, CXCR5- Tph, CXCR5-ICOS+PD-1+ Tph, Tph2 subtypes and Tfh2 subtypes response to allergens.

Associations of concurrent early-life famine exposure and adulthood obesity with type 2 diabetes mellitus in middle-aged Chinese.

BACKGROUND: Evidence has shown that early-life famine exposure and obesity in adulthood are independently associated with the risk of type 2 diabetes mellitus (T2DM). However, few studies had revealed the combined effect of these risk factors. METHODS: Two sets of groups from the China Health and Retirement Longitudinal Study (CHARLS) were selected. The fetal-exposure group born in 1959-1961 from 2011 wave (N = 958) and nonexposure group born in 1963-1965 from 2015 wave (N = 1540) were selected as Comparison 1. The early childhood-exposure group born in 1955-1957 from 2011 wave (N = 1510) and fetal-exposure group born in 1959-1961 from 2015 wave (N = 943) were Comparison 2. Logistic regressions were applied to examine the associations of different famine exposure periods and obesity patterns with T2DM risk. RESULTS: Compared with nonexposed participants without central overweight/obesity in adulthood, central overweight/obesity in adulthood together with nonexposure (odds ratio [OR]: 1.89, 95% confidence interval [CI]: 1.19-3.00) or fetal-exposure (OR: 1.99, 95% CI: 1.23-3.23) was associated with higher risks of T2DM. Compared with the early childhood-exposure group, the fetal-exposed participants showed higher risks of T2DM (OR: 1.30, 95% CI: 1.02-1.66). The coexistence of fetal famine exposure and central overweight/obesity in adulthood was associated with higher risks of T2DM (OR: 1.82, 95% CI: 1.19-2.79). Consistent associations were observed among males and participants from less severely affected areas. CONCLUSIONS: In conclusion, central overweight/obesity in adulthood is associated with the increased risk of T2DM, but the effect of early-life famine exposure is not very clear.

Development and Mechanism Investigation of Novel Thioacetalized Indoles as Antiphytoviral Agents.

Potato virus Y (PVY) is a highly destructive pathogen that infects Solanum tuberosumvL., commonly known as potato, a crop that produces one of the most crucial food staples of the world. The PVY viral infection can considerably reduce the yield and quality of potatoes, thereby causing significant economic ramifications. Given the unsatisfactory performance of commercially available antiviral agents against PVY, we synthesized a series of novel indole-derived compounds followed by their bioevaluation and investigation of the mechanisms governing their anti-PVY activity. These indole-based derivatives contain dithioacetal as a key chemical moiety, and most of them exhibit promising anti-PVY activities. In particular, compound B2 displays remarkable in vivo protective and inactivating properties, with half-maximal effective concentration (EC50) values of 209.3 and 113.0 µg/mL, respectively, in stark contrast to commercial agents such as ningnanmycin (EC50 = 281.4 and 136.3 µg/mL, respectively) and ribavirin (EC50 = 744.8 and 655.4 µg/mL, respectively). The mechanism using which B2 enhances plant immune response to protect plants from PVY is elucidated using enzyme activity tests, real-time quantitative polymerase chain reaction (RT-qPCR), and proteomics techniques. This study aims to pave the way for developing candidate pesticides and related molecules using antiphytoviral activity.

Workplace violence against COVID-19 front-line healthcare workers versus non-front-line in Hangzhou, China: a cross-sectional study.

OBJECTIVES: Workplace violence (WPV) against healthcare workers (HCWs) is a global issue. Our research aimed to elucidate the status and associated factors of WPV among front-line/non-front-line HCWs during the COVID-19 pandemic. DESIGN: This cross-sectional study was conducted among HCWs in Hangzhou City through multistage sampling from December 2020 to January 2021. PARTICIPANTS: This study included 14 909 valid samples (N=3748 front-line HCWs and N=11 161 non-front-line HCWs). PRIMARY AND SECONDARY OUTCOME MEASURES: We assessed the WPV status by Chinese version of WPV questionnaire. Binary logistic regression model was established to examine the associated factors of front-line/non-front-line HCWs experiencing WPV. RESULTS: The total WPV prevalence equalled 37.25% for front-line HCWs and 27.73% for non-front-line HCWs. Among front-line HCWs, females were less likely to experience WPV (OR 0.837, 95% CI 0.710 to 0.988), while individuals who were undergraduate (OR 1.251, 95% CI 1.061 to 1.541) and had higher professional title (intermediate: OR 1.475, 95% CI 1.227 to 1.772; advanced: OR 1.693, 95% CI 1.294 to 2.216) were more likely to suffer from WPV; for non-front-line HCWs, individuals who aged over 50 years old (OR 0.721, 95% CI 0.563 to 0.969), had worked between 10 and 19 years (OR 0.847, 95% CI 0.749 to 0.958) and worked in the non-graded hospital (OR 0.714, 95% CI 0.614 to 0.832) had less chance to experience WPV, while individuals who had higher educational level (undergraduate: OR 1.323, 95% CI 1.179 to 1.484; ≥graduate: OR 1.519, 95% CI 1.217 to 1.895), were nurse (OR 1.142, 95% CI 1.031 to 1.265), and had higher professional title (intermediate: OR 1.458, 95% CI 1.297 to 638; advanced: OR 1.928, 95% CI 1.607 to 2.313) were more inclined to suffer from WPV (p all<0.05). CONCLUSIONS: This study indicates that the prevalence of WPV among front-line HCWs is significantly higher than among non-front-line HCWs. Policy-makers should prioritise COVID-19 front-line HCWs, especially those with high educational levels and professional titles.

Enhancing doctor-patient relationships in community health care institutions: the Patient Oriented Four Habits Model (POFHM) trial-a stepped wedge cluster randomized trial protocol.

BACKGROUND: The poor relationship between doctors and patients is a long-standing, global problem. However, current interventions tend to focus on the training of physicians, while patient-targeted interventions still need to be improved. Considering that patients play a significant role in outpatient consultations, we developed a protocol to assess the effectiveness of the Patient Oriented Four Habits Model (POFHM) in improving doctor-patient relationships. METHODS: A cross-sectional incomplete stepped-wedge cluster randomized trial design will be conducted in 8 primary healthcare institutions (PHCs). Following phase I of "usual care" as control measures for each PHC, either a patient- or doctor-only intervention will be implemented in phase II. In phase III, both patients and doctors will be involved in the intervention. This study will be conducted simultaneously in Nanling County and West Lake District. The primary outcomes will be evaluated after patients complete their visit: (1) patient literacy, (2) sense of control and (3) quality of doctor-patient communication. Finally, a mixed-effects model and subgroup analysis will be used to evaluate the effectiveness of the interventions. DISCUSSION: Fostering good consultation habits for the patient is a potentially effective strategy to improve the quality of doctor-patient communication. This study evaluates the implementation process and develops a rigorous quality control manual using a theoretical domain framework under the collective culture of China. The results of this trial will provide substantial evidence of the effectiveness of patient-oriented interventions. The POFHM can benefit the PHCs and provide a reference for countries and regions where medical resources are scarce and collectivist cultures dominate. TRIAL REGISTRATION: AsPredicted #107,282 on Sep 18, 2022; https://aspredicted.org/QST_MHW.

Design and synthesis of novel PPO-inhibiting pyrimidinedione derivatives safed towards cotton.

Developing innovative and effective herbicides is of utmost importance since weed management has become a worldwide agricultural production concern, resulting in severe economic losses every year. In this study, a series of new pyrimidinedione compounds were developed via combination of pyrimidinediones with N-phenylacetamide moiety. The herbicidal activity test (37.5-150 g of ai/ha) indicated that most of the new derivatives exhibited excellent herbicidal activity against dicotyledonous weeds, but less against grasses. Among them, compound 34 was identified as the best postemergence herbicidal activities against six species of weeds (Amaranthus retrof lexus, AR; Abutilon theophrasti, AT; Veronica polita, VP; Echinochloa crusgalli, EC; Digitaria sanguinalis, DS; Setaria viridis, SV), which were comparable to the commercial control agent saflufenacil (≥90%). The protoporphyrinogen oxidase (PPO; EC. 1.3.3.4) activity experiment suggested that compound 34 could significantly reduce the PPO content in weeds, the relative expression levels of the PPO gene were verified by real-time quantitative polymerase chain reaction (RT-qPCR), and the results were consistent with the trend of the enzyme activity data. Molecular docking showed that compound 34 could occupy the PPO enzyme catalytic substrate pocket, which played an excellent inhibitory effect on the activity of receptor protein. Meanwhile, the tolerance of compound 34 to cotton was better than that of the commercial agent saflufenacil at 150 g of ai/ha. Thus, compound 34 exhibits the potential to be a new PPO herbicide for weed control in cotton fields. This study provided a basis for the subsequent structural modification and mechanism research of pyrimidinedione derivatives.

Identification of diagnostic biomarks and immune cell infiltration in ulcerative colitis.

We aimed to explore diagnostic biomarks and immune cell infiltration characteristics in ulcerative colitis (UC). We used the dataset GSE38713 as the training set and dataset GSE94648 as the test set. A total of 402 differentially expressed genes (DEGs) were obtained from GSE38713. Annotating, visualizing, and integrating discovery of these differential genes was performed using Gene Ontology (GO), Kyoto Gene and Genome Encyclopedia Pathway (KEGG), and Gene Set Enrichment Analysis (GSEA). Protein-protein interaction networks were constructed from the STRING database, and protein functional modules were identified using the CytoHubba plugin of Cytoscape. Random forest and LASSO regression were used to screen for UC-related diagnostic markers, and ROC curves were generated to validate their diagnostic value. The composition of 22 immune cells was analyzed, and the immune cell infiltration in UC was analyzed using CIBERSORT. Results: Seven diagnostic markers associated with UC were identified: TLCD3A, KLF9, EFNA1, NAAA,WDR4, CKAP4, and CHRNA1. Immune cell infiltration assessment revealed that macrophages M1, activated dendritic cells, and neutrophil cells infiltrated relatively more compared to normal control samples. Our results suggest a new functional feature of UC and suggest potential biomarkers for UC through comprehensive analysis of integrated gene expression data.

Regional characteristics and spatial correlation of haze pollution: Interpretative system analysis in cities of Fenwei Plain in China.

Urban agglomeration is an important model for promoting global economic development and has made important contributions to global economic integration. However, as the core area of urbanization and industrialization, urban agglomerations also contribute to air pollutant emissions primarily due to the agglomeration of population and industry. The mutual influence of air pollution between different cities in urban agglomerations has brought significant challenges to global environmental governance. The Fenwei Plain is one of the most severely polluted areas in China. We collected daily average PM2.5 concentration data of 11 cities in the Fenwei Plain, China in 2019. We then developed an interpretive structural model to statistically analyze the spatial correlation and hierarchical transmission of haze pollution between the 11 cities. The results showed that haze pollution has a strong systematic correlation between the 11 cities, and a regional haze pollution community has formed throughout the region. Haze pollution also exhibits evident transmission and spatial correlations between the cities. The transmission starts from Baoji and ends at Sanmenxia, with mutual interactions between the cities of Xi'an, Xianyang, Weinan, Tongchuan, Jinzhong, Lvliang, Linfen, Yuncheng, and Luoyang. Thus, air pollution prevention and control in the Fenwei Plain should consider the spatial correlation of haze pollution between different cities, especially in autumn and winter, and should rationally be implemented in key urban cluster areas. We recommend building a coordinated governance between cities to improve the overall air quality. Our findings shed a light for coordinated pollution management in urban agglomerations worldwide.

Novel 1,3,4-oxadiazole sulfonate/carboxylate flavonoid derivatives: synthesis and biological activity.

BACKGROUND: With the long-term use of traditional bactericides and antiviral agents, drug resistance has become increasingly prominent, resulting in impaired crop growth and yields. Based on this, the introduction of small molecular active groups into natural products has become the direction of research for green pesticides. RESULTS: In this study, novel 1,3,4-oxadiazole sulfonate/carboxylate flavonoid derivatives were explored. Among them, D4 exhibited good inhibitory effects on plant bacteria. It is worth mentioning that D4 (15 µg ml-1 ) exhibited an excellent median effective concentration (EC50 ) value against Xanthomonas oryzae pv. oryzae (Xoo), which was better than bismerthiazol (73 µg ml-1 ) and thiodiazole copper (100 µg ml-1 ). The EC50 for D4 was much lower than the two positive controls (bismerthiazol, thiodiazole copper), making D4 more potent in this assay of bacterial growth inhibition. In addition, mechanism research using scanning electron microscopy revealed that D4 could cause deformation or rupture of the cell membranes of Xoo and Pseudomonas syringae pv. actinidiae. Moreover, D4 exhibited the best EC50 for in vivo curative (132 µg ml-1 ) and protective (101 µg ml-1 ) activities against tobacco mosaic virus, which were more effective than ningnanmycin. Microscale thermophoresis data suggested that D4 [dissociation constant (Kd ) = 0.038 ± 0.011 µmol L-1 ] exhibited a stronger binding capacity than the control agent ningnanmycin (Kd = 4.707 ± 2.176 µmol L-1 ). CONCLUSION: The biological activity data and mode of action demonstrated that D4 had the best antibacterial and antiviral effects. Compound D4 discovered in the current work may be a very promising agricultural drug. © 2022 Society of Chemical Industry.

Efficacy of oral fecal microbiota transplantation in recurrent bowel disease: A protocol for systematic review and meta-analysis.

BACKGROUND: Recurrent bowel disease (RBD) refers to the chronic, recurrent intestinal diseases, including recurrent Clostridium Difficile Infection (rCDI), inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), etc., these diseases have similar clinical characteristics, that is, abdominal pain, diarrhea, repeated attacks, prolonged recovery, etc. Clinically, there are relevant reports on the use of oral capsule fecal microbiota transplantation (oFMT) to treat RBD. However, both the advantages and disadvantages of clinical efficacy have been reported; there are some contradictions, the study sample size is too small, and the purpose of this systematic review was to evaluate the efficacy and safety of oral capsule fecal microbiota transplantation in the treatment of RBD. METHODS: This systematic review will include articles identified through electronic searches of the PubMed, EMbase, and Cochrane Library. From inception to July 1, 2022. Two reviewers will independently search the database to conduct data extraction and assessment of study quality. Based on heterogeneity tests, data will be integrated using fixed or random effect models. RevMan V.5.4 will be used for data analysis. The results are expressed as the risk ratio of dichotomous data and the mean difference of continuous data. RESULTS: We analyzed the clinical remission or cure rate, IBS-SSS, quality of life, anxiety, depression, total adverse effects, and total severe adverse effects (TSAE) in patients with RBD. CONCLUSION: This systematic review evaluated the efficacy and safety of oFMT in the treatment of RBD to provide more comprehensive evidence.

Design, Synthesis, and Biological Evaluation of Novel 1,4-Pentadien-3-one Derivatives Containing a Sulfonamide Moiety.

Novel 1,4-pentadien-3-one derivatives containing a sulfonamide moiety were synthesized, and their antifungal, antibacterial, and antiviral activities were verified. These compounds exhibited better activity against five bacteria, with EC50 values ranging from 9.6 to 60.1 µg/mL, prominently, which are superior to those of the commercial agent. A great amount of compounds had excellent fungicidal activity in vitro at 100 µg/mL. Strikingly, compound E6 exhibited moderate activity against Phytophthora litchii than azoxystrobin, with the EC50 value of compound E6 (0.5 µg/mL) drawing near azoxystrobin (0.3 µg/mL). Furthermore, compound E17 had a marked impact on in vivo anti-tobacco mosaic virus, according to the data of microscale thermophoresis, with a Kd value of the intermolecular binding force of 0.002 ± 0.001 µM, which was better than the commercial agent of ningnanmycin (Kd = 0.121 ± 0.031 µM). In addition, the results of these studies suggest that the use of active splicing can improve the biological activity of natural compounds and provide further complement to the development of novel pesticides.

Temporal trends in pulse pressure and mean arterial pressure in Chinese children and adolescents over two decades (1991-2015).

Background: Pulse pressure (PP) and mean arterial pressure (MAP) are well-established markers of cardiovascular risk. In this study, we aimed to assess the temporal trend and associated factors of PP and MAP in Chinese children and adolescents. Methods: From the China Health and Nutrition Survey 1991-2015, a total of 11,123 children and adolescents aged 7-17 years were included. Stratified analyses and generalized estimating equation (GEE) were conducted to compare the trends of PP and MAP by age and sex over two decades, along with the calculation of average relative increase (ARI). Moreover, multivariable linear regression was used to estimate the associated factors of PP and MAP. Results: During 1991-2015, upward trends were observed in both PP and MAP levels, with ARI of 0.30 and 0.34%, respectively. PP was higher in boys [PP1991 33.9 mmHg (95%CI, 33.40-34.33) to PP2015 35.4 mmHg (34.74-36.15)] than in girls [PP1991 33.3 mmHg (32.83-33.72) to PP2015 34.3 mmHg (33.59-34.99)]. PP was also higher in participants aged 13-17 years [PP1991 36.1 mmHg (35.63-36.62) to PP2015 38.3 mmHg (37.35-39.21)] than in those aged 7-12 years [PP1991 31.5 mmHg (31.09-31.88) to PP2015 33.7 mmHg (33.16-34.30)]. Similar results were found in MAP. Participants with high economic status, general obesity and central obesity, were more likely to have wider PP (ß higheconomicstatus = 0.60, 95% CI, 0.19-1.02; ß generalobesity = 1.38, 0.87-1.89; ß centralobesity = 1.34, 0.70-1.97; all P-values < 0.001) and higher MAP (ß higheconomicstatus = 0.82, 0.38-1.26; ß generalobesity = 2.88, 2.33-3.42; ß centralobesity = 3.14, 2.47-3.80; all P-values < 0.001). Body mass index (BMI) and waist circumference (WC) were positively correlated with PP (ß BMI = 0.18, 0.13-0.24; ß WC = 0.10, 0.08-0.12; both P-values < 0.001) and MAP (ß BMI = 0.43, 0.37-0.49; ß WC = 0.20, 0.18-0.22; both P-values < 0.001). In addition, rural setting and glucose level were positively associated with PP (both P < 0.05), while north region residency, uric acid, and total cholesterol were found to be positively associated with MAP (all P < 0.05). Conclusion: PP and MAP levels have been increasing dramatically in Chinese children and adolescents over the last two decades. Age, sex, economic status, geographic factors, anthropometric and cardiometabolic factor were positively associated with PP and MAP in pediatric population.

DSF/Cu induces antitumor effect against diffuse large B-cell lymphoma through suppressing NF-κB/BCL6 pathways.

BACKGROUND: The B-cell lymphoma 6 (BCL6) oncogene is required for the survival of diffuse large B-cell lymphoma (DLBCL), which is incurable using conventional chemotherapy. Thus, it is imperative to improve the survival of patients with DLBCL. Disulfide (DSF) has been shown to have anticancer effects, but its effect on DLBCL remains unclear. METHODS: Four DLBCL cell lines (OCI-LY1, OCI-LY7, OCI-LY10 and U2932) and primary DLBCL cells from eight newly diagnosed DLBCL patients were pretreated with DSF alone or in combination with Cu. Cell morphology was observed under microscope. Flow cytometry was performed to evaluate the cell apoptosis, cell cycle, the mitochondrial membrane potential and the intracellular accumulation of reactive oxygen species (ROS). The protein expression was respectively measured by flow cytometry and western blotting. RESULTS: DSF or DSF/Cu exhibited a marked inhibitory effect on the growth of DLBCL cells, accompanied by cell cycle arrest at the G0/G1 phase. Meanwhile, DSF or DSF/Cu significantly induced DLBCL cells apoptosis. Further study revealed that DSF or DSF/Cu promoted apoptosis by inhibiting NF-κB signaling pathway. Interestingly, DSF/Cu significantly reduced BCL6 and AIP levels. In addition, DSF significantly up-regulate p53 protein in OCI-LY7 and OCI-LY10 while down-regulate p53 protein in OCI-LY1 and U2932. CONCLUSION: These results provided evidence for the anti-lymphoma effects of DSF on DLBCL and suggested that DSF has therapeutic potential to DLBCL.

Socioeconomic Burden of Bloodstream Infections Caused by Carbapenem-Resistant Enterobacteriaceae.

BACKGROUND: Although infection with carbapenem-resistant Enterobacteriaceae (CRE) has become an urgent public health threat worldwide, the socioeconomic burden of CRE bloodstream infection (BSI) remains to be clarified. METHODS: This retrospective study included all patients infected with Escherichia coli or Klebsiella pneumoniae who were hospitalized for BSI from 2013 to 2015. Socioeconomic burden, including direct and indirect economic burden, was compared in patients infected with carbapenem-sensitive Enterobacteriaceae (CSE) and CRE following 1:1 propensity score matching (PSM) to control for confounding variables. RESULTS: Data from 879 patients with Enterobacteriaceae BSI were evaluated, including 152 (17.3%) patients infected with CRE and 727 (82.7%) infected with CSE. PSM yielded 112 pairs of 224 patients. Median hospital length of stay did not differ significantly in the CRE and CSE groups (35 vs 29 days, P = 0.089), but in-hospital 28-day mortality rate was significantly higher in patients infected with CRE than with CSE (45.5% vs 32.1%, P = 0.040). Median direct economic burden was significantly greater in patients with CRE-BSI than with CSE-BSI during hospitalization ($24,940.1 vs 16,864.0, P = 0.017) but not during the period after infection ($10,403.4 vs 8498.0, P = 0.178). Drug expenditure accounted for the largest proportion of costs in both groups. The median disability-adjusted life year (DALY) was higher in CRE-BSI than in CSE-BSI patients, but the difference was not statistically significant (7.9 vs 6.7 years, P = 0.190). Median indirect economic burden did not differ significantly in these two groups ($3848.5 vs 1139.9, P = 0.304), although indirect economic burden increased significantly from 2013 to 2015 in patients with CRE-BSI. CONCLUSION: Carbapenem resistance had a major impact on the clinical and socioeconomic burden of patients with Enterobacteriaceae BSI. The higher mortality rate in patients with CRE-BSI was associated with increased direct healthcare burden and indirect socioeconomic loss.

Socioeconomic burden of bloodstream infections caused by carbapenem-resistant and carbapenem-susceptible Pseudomonas aeruginosa in China.

OBJECTIVES: Drug resistance in Pseudomonas aeruginosa (PAE) is a serious health threat. Additionally, it is important to understand the associated socioeconomic burden. METHODS: Clinical information and hospital cost data for patients with PAE bloodstream infections (BSIs) in a tertiary teaching hospital (2011-2016) were collected retrospectively to estimate the direct economic burden. Socioeconomic loss incurred by patients was calculated using the human capital approach combined with estimating disability-adjusted life years (DALYs). Differences in socioeconomic burden between BSIs caused by carbapenem-resistant (CR) and carbapenem-susceptible (CS) PAE were compared. RESULTS: This study included data for 220 patients, of which were 29.5% (65/220) CR-PAE BSIs. The median direct economic burden of patients following CR-PAE BSI was significantly higher than following CS-PAE BSI ($5005.94 vs. $1462.86; P < 0.001). The median DALY loss was significantly higher in the CR-PAE group compared with CS-PAE group (0.024 vs. 0.008; P = 0.001). The median indirect socioeconomic loss of patients in the CR-PAE group tended to be significantly higher than in the CS-PAE group ($64.06 vs. $29.71; P = 0.011). The annual economic burden of CR-PAE is higher (up to >1.5 times) than the Chinese annual per capita GDP. CONCLUSION: The economic burden of PAE BSIs is significant, irrespective of carbapenem resistance. The direct economic burden of CR-PAE BSI was at least three-fold that of CS-PAE BSI. The DALY loss caused by CR-PAE BSI is three-fold that caused by CS-PAE BSI. The indirect socioeconomic loss caused by CR-PAE BSI is more than twice that of CS-PAE BSI.

Economic Burden of Patients with Bloodstream Infections Caused by Extended-Spectrum ß-Lactamase-Producing Escherichia coli.

BACKGROUND: The prevalence of infections with extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-EC) is increasing worldwide, but the economic impact of ESBL-EC bloodstream infection (BSI) has not been comprehensively evaluated. PATIENTS AND METHODS: A retrospective cohort including patients hospitalized at a tertiary hospital between January 2013 and December 2016 who were confirmed with a BSI of ESBL-EC or non-ESBL-EC was set. Clinical data and medical costs were collected by chart review of electronic and paper medical records. The economic burden was evaluated with disability-adjusted life years (DALYs). RESULTS: A total of 580 patients with E. coli BSI, comprising 333 patients (57.4%) with ESBL-EC BSI and 247 patients (42.6%) with non-ESBL-EC BSI, were identified. There were no significant differences in comorbidity and severity of patients between ESBL-EC and non-ESBL-EC BSI. The median length of stay (LOS) after bacteremia was 12 days for ESBL-EC (interquartile range, 7 to 21) versus 11 days for non-ESBL-EC (interquartile range, 7 to 21) (P = 0.38), and appropriate empirical antimicrobial therapy occurred in 87.4% versus 89.9% (P = 0.353). The mortalities were 20.1% versus 17.4% (P = 0.41). Patients with ESBL-EC did not have significantly different in-hospital medical costs to those with non-ESBL-EC (median, $8048.68 vs $7476.84, respectively, with a difference of $571.84, P = 0.321). In the non-ESBL-EC group, 247 patients lost 531.05 DALYs in total, with an average of 2.15 DALYs per person, while in the ESBL-EC group, 333 patients lost 692.64 DALYs in total, with an average of 2.08 DALYs per person. There is no significant difference in average DALYs (P = 0.343). CONCLUSION: In conclusion, patients with BSI due to ESBL-EC did not cost more than patients with BSI due to non-ESBL-EC. This phenomenon may be attributed to timely and effective antibiotic treatment, but the initial empiric therapy with second- or third-line antibiotics in non-ESBL-EC BSI should be corrected.

A Retrospective Analysis of Risk Factors and Outcomes of Carbapenem-Resistant Klebsiella pneumoniae Bacteremia in Nontransplant Patients.

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKP) has become a major problem among nosocomial infections, and it is a serious threat to patients. The clinical characteristics and outcome of CRKP bloodstream infection (BSI) in nontransplant patients remains unelucidated. The aim of this study was as follows: identify the risk factors of CRKP infection; generate new ideas for prevention; and generate new ideas for the most effective therapeutic management in nontransplant patients. METHODS: The study retrospectively analyzed the clinical and microbiological data of nontransplant patients with K pneumoniae (KP) bacteremia from January 2013 to December 2015 to identify risk factors, clinical features, and outcomes using multivariate logistic regression analysis. RESULTS: Of the 371 patients with KP-BSI in nontransplant patients included in this study, 28.0% (N = 104) had CRKP. The 28-day mortality was higher in patients infected with CRKP (55.8%) than in those with carbapenem-susceptible KP (13.9%) (P < .001). Multivariate analysis showed previous gastric catheterization, previous use of carbapenems, hypoproteinemia, and high Acute Physiologic Assessment and Chronic Health Evaluation II scores as independent risk factors for CRKP-BSIs. Carbapenem-resistant KP infection, severe illness, and tigecycline therapy were independent risk factors for death from KP-BSIs. Taken together, inappropriate antibiotic treatment both in empirical and definitive therapy and imipenem minimum inhibitory concentrations (MICs) of >8 mg/L were associated with poor clinical outcome. CONCLUSIONS: Nontransplant patients with CRKP-BSI had higher mortality. Carbapenems exposure was an independent risk factor for CRKP infection. Imipenem MICs of >8 mg/L, tigecycline therapy, and inappropriate treatments increased the 28-day mortality of KP-BSI patients.

Study on lncRNA ADAMTS9-AS2 promoting invasion and metastasis of salivary adenoid cystic carcinoma / 口腔疾病防治

Objective@#To investigate the role of lncRNAs in the invasion and metastasis of salivary adenoid cystic carcinoma (SACC) cells.@*Methods@#With SACC-LM as the experimental group and SACC83 as the control group, lncRNA chips were used to screen the differentially expressed lncRNAs. The differentially expressed lncRNAs were further verified by real-time quantitative RT-PCR (qRT-PCR). The invasion and migration abilities of the adenoid cystic carcinoma cell lines before and after transfection with lncRNA siRNAs were detected by invasion and migration experiments. The clinicopathological features and prognosis of patients with different expression of lncRNAs and SACC were analyzed.@*Results@#The microarray showed that ADAMTS9-AS2 was highly expressed in the SACC-LM cells. Real-time quantitative RT-PCR further confirmed that ADAMTS9-AS2 was significantly upregulated in the SACC-LM cells. Invasion and migration experiments showed that the invasion and migration were significantly reduced after the expression level of ADAMTS9-AS2 was downregulated (P ＜ 0.001). Analysis of the clinicopathological data showed that ADAMTS9-AS2 was highly expressed in SACC. High expression of ADAMTS9-AS2 was associated with poor prognosis and a high tumor metastasis rate in SACC patients.@*Conclusion @#High expression of ADAMTS9-AS2 promotes the migration and invasion of SACC cells. ADAMTS9-AS2 is upregulated in the SACC tissues and is related to a high metastasis rate and poor prognosis.

Comprehensive Genome Analysis of Carbapenem-Resistant Raoultella spp. strains, an Emerging Multidrug-Resistant Bacteria in Hospitals.

We report the characterization of six carbapenem-resistant Raoultella spp.(CRRS) in our hospital and a genomic analysis of 58 publicly available isolates. CRRS isolates are sporadically identified around the world and different transposons carrying carbapenemases were the resistant mechanisms. Mobile genetic elements play an important role in acquiring antibiotic resistant genes from the hospital. An improved understanding of these transposon and targeted control measures will be very valuable to prevent the CRRS dissemination.

Pyrazolo[3,4-d]pyrimidine derivatives containing a Schiff base moiety as potential antiviral agents.

A series of pyrazolo[3,4-d]pyrimidine derivatives containing a Schiff base moiety were synthesized, characterised, and evaluated for their activity against tobacco mosaic virus (TMV). Biological assays indicated that several of the derivatives exhibited significant activity against TMV. In particularly, compounds 5y and 5aa displayed excellent inactivating activity against TMV, with half maximal effective concentration (EC50) values of 70.3 and 53.65 µg/mL, respectively, which were much better than that of ribavirin (150.45 µg/mL), and 5aa was superior to ningnanmycin (EC50 = 55.35 µg/mL). Interactions of compounds 5y and 5aa with TMV coat protein (TMV-CP) were investigated using microscale thermophoresis and molecular docking. Compounds 5y and 5aa displayed strong binding capability to TMV-CP with dissociation constant (Kd) values of 22.6 and 9.8 µM, respectively. These findings indicate that pyrazolo[3,4-d]pyrimidine derivatives containing a Schiff base may be potential antiviral agents.