Introduction: The prevalence of </span><i><span style="font-family:Verdana;">Klebsiella pneumoniae</span></i><span style="font-family:Verdana;"> has rapidly incr...Introduction: The prevalence of </span><i><span style="font-family:Verdana;">Klebsiella pneumoniae</span></i><span style="font-family:Verdana;"> has rapidly increased in recent years and the distribution differed greatly by region, We aimed to study the relationship between antibiotic resistance and </span><i><span style="font-family:Verdana;">K. pneumoniae</span></i><span style="font-family:Verdana;">, especially carbapenem-resistant </span><i><span style="font-family:Verdana;">Klebsiella pneumoniae</span></i><span style="font-family:Verdana;"> (CRKP) in our tertiary hospitals from 2014 to 2018.</span></span><span style="font-family:""> </span><span style="font-family:""><span style="font-family:Verdana;">Methodology: The antibiotic consumption data of </span><i><span style="font-family:Verdana;">K. pneumoniae</span></i><span style="font-family:Verdana;"> were expressed as the defined daily dose (DDD) per 100 inpatient days</span></span><span style="font-family:""> </span><span style="font-family:""><span style="font-family:Verdana;">(DDDs). </span><i><span style="font-family:Verdana;">K. pneumoniae</span></i><span style="font-family:Verdana;"> which isolated from clinical samples in</span><span style="font-family:Verdana;"> hospital between January 2014 and December 2018 were retrospectively analyzed, and the correlation between antibiotic resistance rate and antibiotic frequency was analyzed.</span></span><span style="font-family:""> </span><span style="font-family:""><span style="font-family:Verdana;">Results: From 2014 to 2018, a total of 2295 strains of </span><i><span style="font-family:Verdana;">K. pneumoniae</span></i><span style="font-family:Verdana;"> were isolated, with the detection rates of 8.2%, 9.2%, 11.9%, 13.4% and 14.0%. There were 423 strains of CRKP, with the detection rates of 7.5%, 5.8%, 17</span></span><span style="font-family:Verdana;">.</span><span style="font-family:""><span style="font-family:Verdana;">8% 24.2% and 25.2% respectively. </span><i><span style="font-family:Verdana;">K. pneumoniae</span></i><span style="font-family:Verdana;"> showed di</span></span><span style="font-family:Verdana;">fferent degrees of resistance to antibiotics and showed an increasing trend year by year to carbapenems. The resistance rate of imipenem was 2.5%</span><span style="font-family:Verdana;">, </span><span style="font-family:Verdana;">2.8%</span><span style="font-family:Verdana;">, </span><span style="font-family:Verdana;">9.9%</span><span style="font-family:Verdana;">, </span><span style="font-family:Verdana;">12.3%</span><span style="font-family:Verdana;">, </span><span style="font-family:Verdana;">13.4%, and the resistance rate of meropenem was 2.0%</span><span style="font-family:Verdana;">, </span><span style="font-family:Verdana;">3.0%</span><span style="font-family:Verdana;">, </span><span style="font-family:Verdana;">8.8%</span><span style="font-family:Verdana;">, </span><span style="font-family:Verdana;">12.6%</span><span style="font-family:Verdana;">, </span><span style="font-family:""><span style="font-family:Verdana;">12.7%, respectively. The resistance rate of most other drugs decreased. The DDDs values of cefoperazone/sulbactam, piperacillin-tazobactam and gentamicin showed a strong positive correlation with </span><i><span style="font-family:Verdana;">K. pneumoniae</span></i><span style="font-family:Verdana;"> drug resistance rate</span></span><span style="font-family:""> </span><span style="font-family:Verdana;">(r</span><span style="font-family:""> </span><span style="font-family:Verdana;">></span><span style="font-family:""> </span><span style="font-family:Verdana;">0.8, P</span><span style="font-family:""> </span><span style="font-family:Verdana;"><</span><span style="font-family:""> </span><span style="font-family:Verdana;">0.05)</span><span style="font-family:Verdana;">. </span><span style="font-family:""><span style="font-family:Verdana;">Conclusions: The detection rate of </span><i><span style="font-family:Verdana;">K. pneumoniae</span></i><span style="font-family:Verdana;"> and CRKP increased year by year, which was closely related to the dose of antibiotics. Strengthening the management of antimicrobial drugs and standardising the use of antimicrobial prescriptions were of great significance for delaying the emergence of drug-resistant bacteria.展开更多
<span style="font-family:Verdana;">In our study, we aimed to optimize the dosage regimen of Isavuconazole </span><span style="font-family:""><span style="font-family:...<span style="font-family:Verdana;">In our study, we aimed to optimize the dosage regimen of Isavuconazole </span><span style="font-family:""><span style="font-family:Verdana;">against </span><i><span style="font-family:Verdana;">Candida spp. </span></i><span style="font-family:Verdana;">and </span><i><span style="font-family:Verdana;">Aspergillus spp. </span></i><span style="font-family:Verdana;">by Mo</span></span><span style="font-family:Verdana;">n</span><span style="font-family:Verdana;">te Carlo simulation (MSC). Pharmacokinetic parameters and microbiological data of Isavuconazole were collected. Then we used MSC to simulate 10,000 patients analyzed by Crystal Ball to calculate probability of target attainment (PTA) and cumulative fraction of response (CFR). With dosages of 100</span><span style="font-family:""> </span><span style="font-family:Verdana;">mg, 200</span><span style="font-family:""> </span><span style="font-family:Verdana;">mg, and 400</span><span style="font-family:""> </span><span style="font-family:Verdana;">mg in oral group and dosages of 100</span><span style="font-family:""> </span><span style="font-family:Verdana;">mg, and 200</span><span style="font-family:""> </span><span style="font-family:Verdana;">mg in intravenous administration, all have different degree</span><span style="font-family:Verdana;">s</span><span style="font-family:Verdana;"> of antifungal effect. But when the dosage regimen was 50</span><span style="font-family:""> </span><span style="font-family:""><span style="font-family:Verdana;">mg IV, the therapeutic effect of Isavuconazole against </span><i><span style="font-family:Verdana;">Aspergillus spp.</span></i><span style="font-family:Verdana;"> and </span><i><span style="font-family:Verdana;">Candida spp. </span></i><span style="font-family:Verdana;">were not good.展开更多
Non-suicidal self-injury (NS SI) refers to any intentional,self-inflicted behavior that causes direct damage to body tissues (Kerr et al.,2010),and has emerged as a challenging public health issue worldwide,especially...Non-suicidal self-injury (NS SI) refers to any intentional,self-inflicted behavior that causes direct damage to body tissues (Kerr et al.,2010),and has emerged as a challenging public health issue worldwide,especially among adolescents.The most common presentations of NSSI include skin-cutting,severe scratching,and burning (Whitlock et al,2006).展开更多
<strong>Objective:</strong><span style="font-family:""><span style="font-family:Verdana;"> Breast Cancer (BC) is characterized by high complexity and heterogeneity, and...<strong>Objective:</strong><span style="font-family:""><span style="font-family:Verdana;"> Breast Cancer (BC) is characterized by high complexity and heterogeneity, and microRNA (miRNA) is bound up with the occurrence and </span><span style="font-family:Verdana;">development of BC. In this study, we evaluated the prognostic value of</span><span style="font-family:Verdana;"> miR</span><span><span style="font-family:Verdana;">NA in BC. </span><b><span style="font-family:Verdana;">Background:</span></b><span style="font-family:Verdana;"> Breast ductal and lobular cancers are the most </span></span><span style="font-family:Verdana;">common types of Breast Carcinomas (BC) and indicate the high complexity heterogeneity in this disease. Each BC patient has unique morphological and </span><span style="font-family:Verdana;">molecular features. MicroRNAs (miRNAs) play a critical role in human </span><span style="font-family:Verdana;">oncoge</span><span style="font-family:Verdana;">nesis, progression, and prognosis. Our study aimed to identify potential</span><span style="font-family:Verdana;"> prognostic biomarkers of breast ductal and lobular cancers to predict the overall </span><span><span style="font-family:Verdana;">survival outcome. </span><b><span style="font-family:Verdana;">Methods:</span></b><span style="font-family:Verdana;"> All analyzed miRNA sequencing and clinical </span></span><span style="font-family:Verdana;">data were obtained from the Genomic Data Commons Data Porta. edgeR package in R </span><span style="font-family:Verdana;">software was used to analyze the differential miRNA expression profiles</span><span style="font-family:Verdana;">. Com</span><span style="font-family:Verdana;">plete survival information and differentially expressed miRNA expression</span><span style="font-family:Verdana;"> were obtained and the Caret package was used for random division of the samples along with their profiles into two groups (training group and test group). We </span><span style="font-family:Verdana;">performed univariate Cox regression analyses for miRNAs in the training</span><span> </span><span style="font-family:Verdana;">group. We utilized three different web-based tools to identify the targe</span><span style="font-family:Verdana;">t genes </span><span style="font-family:Verdana;">of miRNAs and used the Perl language to evaluate the target genes for</span><span><span style="font-family:Verdana;"> miRNA signature. STRING database was used to assess PPIs. </span><b><span style="font-family:Verdana;">Re</span></b></span><b><span style="font-family:Verdana;">sults:</span></b><span style="font-family:Verdana;"> A total of </span><span style="font-family:Verdana;">304 differentially expressed miRNAs were identified (213 were upregulated </span><span style="font-family:Verdana;">and 91 were downregulated). Among these, nine (hsa-miR-204-5p, hsa-miR-7706, hsa-miR-1247-3p, hsa-miR-20b-3p, hsa-miR-605-5p, hsa-</span><span style="font-family:Verdana;">miR-615-3p, hsa-miR-4652-5p, hsa-miR-9-5p, hsa-miR-2115-5p) </span><span style="font-family:Verdana;">miRNAs </span><span style="font-family:Verdana;">which remarkably correlated with overall survival rate of BC were per</span><span style="font-family:Verdana;">formed by Cox regression analysis and miRNA signature risk score built. And then </span><span style="font-family:Verdana;">we performed the model of BC patients for three years survival risk, the</span><span style="font-family:Verdana;"> AUCs of ROC were 0.804, 0.667, and 0.739 in the training, test, and entire groups, respectively. miRNAs were differentially expressed in tumor-related </span><span style="font-family:Verdana;">biological processes and pathways by functional enrichment and</span><span style="font-family:Verdana;"> bioinformatic analysis. </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> The current study provided novel insights into the mi</span><span style="font-family:Verdana;">RNA-based mRNA network in BC. The nine miRNA and ten hub genes </span><span style="font-family:Verdana;">may be independent prognostic signatures for survival prediction in BC patients.</span></span>展开更多
文摘Introduction: The prevalence of </span><i><span style="font-family:Verdana;">Klebsiella pneumoniae</span></i><span style="font-family:Verdana;"> has rapidly increased in recent years and the distribution differed greatly by region, We aimed to study the relationship between antibiotic resistance and </span><i><span style="font-family:Verdana;">K. pneumoniae</span></i><span style="font-family:Verdana;">, especially carbapenem-resistant </span><i><span style="font-family:Verdana;">Klebsiella pneumoniae</span></i><span style="font-family:Verdana;"> (CRKP) in our tertiary hospitals from 2014 to 2018.</span></span><span style="font-family:""> </span><span style="font-family:""><span style="font-family:Verdana;">Methodology: The antibiotic consumption data of </span><i><span style="font-family:Verdana;">K. pneumoniae</span></i><span style="font-family:Verdana;"> were expressed as the defined daily dose (DDD) per 100 inpatient days</span></span><span style="font-family:""> </span><span style="font-family:""><span style="font-family:Verdana;">(DDDs). </span><i><span style="font-family:Verdana;">K. pneumoniae</span></i><span style="font-family:Verdana;"> which isolated from clinical samples in</span><span style="font-family:Verdana;"> hospital between January 2014 and December 2018 were retrospectively analyzed, and the correlation between antibiotic resistance rate and antibiotic frequency was analyzed.</span></span><span style="font-family:""> </span><span style="font-family:""><span style="font-family:Verdana;">Results: From 2014 to 2018, a total of 2295 strains of </span><i><span style="font-family:Verdana;">K. pneumoniae</span></i><span style="font-family:Verdana;"> were isolated, with the detection rates of 8.2%, 9.2%, 11.9%, 13.4% and 14.0%. There were 423 strains of CRKP, with the detection rates of 7.5%, 5.8%, 17</span></span><span style="font-family:Verdana;">.</span><span style="font-family:""><span style="font-family:Verdana;">8% 24.2% and 25.2% respectively. </span><i><span style="font-family:Verdana;">K. pneumoniae</span></i><span style="font-family:Verdana;"> showed di</span></span><span style="font-family:Verdana;">fferent degrees of resistance to antibiotics and showed an increasing trend year by year to carbapenems. The resistance rate of imipenem was 2.5%</span><span style="font-family:Verdana;">, </span><span style="font-family:Verdana;">2.8%</span><span style="font-family:Verdana;">, </span><span style="font-family:Verdana;">9.9%</span><span style="font-family:Verdana;">, </span><span style="font-family:Verdana;">12.3%</span><span style="font-family:Verdana;">, </span><span style="font-family:Verdana;">13.4%, and the resistance rate of meropenem was 2.0%</span><span style="font-family:Verdana;">, </span><span style="font-family:Verdana;">3.0%</span><span style="font-family:Verdana;">, </span><span style="font-family:Verdana;">8.8%</span><span style="font-family:Verdana;">, </span><span style="font-family:Verdana;">12.6%</span><span style="font-family:Verdana;">, </span><span style="font-family:""><span style="font-family:Verdana;">12.7%, respectively. The resistance rate of most other drugs decreased. The DDDs values of cefoperazone/sulbactam, piperacillin-tazobactam and gentamicin showed a strong positive correlation with </span><i><span style="font-family:Verdana;">K. pneumoniae</span></i><span style="font-family:Verdana;"> drug resistance rate</span></span><span style="font-family:""> </span><span style="font-family:Verdana;">(r</span><span style="font-family:""> </span><span style="font-family:Verdana;">></span><span style="font-family:""> </span><span style="font-family:Verdana;">0.8, P</span><span style="font-family:""> </span><span style="font-family:Verdana;"><</span><span style="font-family:""> </span><span style="font-family:Verdana;">0.05)</span><span style="font-family:Verdana;">. </span><span style="font-family:""><span style="font-family:Verdana;">Conclusions: The detection rate of </span><i><span style="font-family:Verdana;">K. pneumoniae</span></i><span style="font-family:Verdana;"> and CRKP increased year by year, which was closely related to the dose of antibiotics. Strengthening the management of antimicrobial drugs and standardising the use of antimicrobial prescriptions were of great significance for delaying the emergence of drug-resistant bacteria.
文摘<span style="font-family:Verdana;">In our study, we aimed to optimize the dosage regimen of Isavuconazole </span><span style="font-family:""><span style="font-family:Verdana;">against </span><i><span style="font-family:Verdana;">Candida spp. </span></i><span style="font-family:Verdana;">and </span><i><span style="font-family:Verdana;">Aspergillus spp. </span></i><span style="font-family:Verdana;">by Mo</span></span><span style="font-family:Verdana;">n</span><span style="font-family:Verdana;">te Carlo simulation (MSC). Pharmacokinetic parameters and microbiological data of Isavuconazole were collected. Then we used MSC to simulate 10,000 patients analyzed by Crystal Ball to calculate probability of target attainment (PTA) and cumulative fraction of response (CFR). With dosages of 100</span><span style="font-family:""> </span><span style="font-family:Verdana;">mg, 200</span><span style="font-family:""> </span><span style="font-family:Verdana;">mg, and 400</span><span style="font-family:""> </span><span style="font-family:Verdana;">mg in oral group and dosages of 100</span><span style="font-family:""> </span><span style="font-family:Verdana;">mg, and 200</span><span style="font-family:""> </span><span style="font-family:Verdana;">mg in intravenous administration, all have different degree</span><span style="font-family:Verdana;">s</span><span style="font-family:Verdana;"> of antifungal effect. But when the dosage regimen was 50</span><span style="font-family:""> </span><span style="font-family:""><span style="font-family:Verdana;">mg IV, the therapeutic effect of Isavuconazole against </span><i><span style="font-family:Verdana;">Aspergillus spp.</span></i><span style="font-family:Verdana;"> and </span><i><span style="font-family:Verdana;">Candida spp. </span></i><span style="font-family:Verdana;">were not good.
基金supported by the National Key Basic Research Program of China(No.2016YFC1307100)the Program of Health and Family Planning Commission in Zhejiang Province(No.2020KY548),China。
文摘Non-suicidal self-injury (NS SI) refers to any intentional,self-inflicted behavior that causes direct damage to body tissues (Kerr et al.,2010),and has emerged as a challenging public health issue worldwide,especially among adolescents.The most common presentations of NSSI include skin-cutting,severe scratching,and burning (Whitlock et al,2006).
文摘<strong>Objective:</strong><span style="font-family:""><span style="font-family:Verdana;"> Breast Cancer (BC) is characterized by high complexity and heterogeneity, and microRNA (miRNA) is bound up with the occurrence and </span><span style="font-family:Verdana;">development of BC. In this study, we evaluated the prognostic value of</span><span style="font-family:Verdana;"> miR</span><span><span style="font-family:Verdana;">NA in BC. </span><b><span style="font-family:Verdana;">Background:</span></b><span style="font-family:Verdana;"> Breast ductal and lobular cancers are the most </span></span><span style="font-family:Verdana;">common types of Breast Carcinomas (BC) and indicate the high complexity heterogeneity in this disease. Each BC patient has unique morphological and </span><span style="font-family:Verdana;">molecular features. MicroRNAs (miRNAs) play a critical role in human </span><span style="font-family:Verdana;">oncoge</span><span style="font-family:Verdana;">nesis, progression, and prognosis. Our study aimed to identify potential</span><span style="font-family:Verdana;"> prognostic biomarkers of breast ductal and lobular cancers to predict the overall </span><span><span style="font-family:Verdana;">survival outcome. </span><b><span style="font-family:Verdana;">Methods:</span></b><span style="font-family:Verdana;"> All analyzed miRNA sequencing and clinical </span></span><span style="font-family:Verdana;">data were obtained from the Genomic Data Commons Data Porta. edgeR package in R </span><span style="font-family:Verdana;">software was used to analyze the differential miRNA expression profiles</span><span style="font-family:Verdana;">. Com</span><span style="font-family:Verdana;">plete survival information and differentially expressed miRNA expression</span><span style="font-family:Verdana;"> were obtained and the Caret package was used for random division of the samples along with their profiles into two groups (training group and test group). We </span><span style="font-family:Verdana;">performed univariate Cox regression analyses for miRNAs in the training</span><span> </span><span style="font-family:Verdana;">group. We utilized three different web-based tools to identify the targe</span><span style="font-family:Verdana;">t genes </span><span style="font-family:Verdana;">of miRNAs and used the Perl language to evaluate the target genes for</span><span><span style="font-family:Verdana;"> miRNA signature. STRING database was used to assess PPIs. </span><b><span style="font-family:Verdana;">Re</span></b></span><b><span style="font-family:Verdana;">sults:</span></b><span style="font-family:Verdana;"> A total of </span><span style="font-family:Verdana;">304 differentially expressed miRNAs were identified (213 were upregulated </span><span style="font-family:Verdana;">and 91 were downregulated). Among these, nine (hsa-miR-204-5p, hsa-miR-7706, hsa-miR-1247-3p, hsa-miR-20b-3p, hsa-miR-605-5p, hsa-</span><span style="font-family:Verdana;">miR-615-3p, hsa-miR-4652-5p, hsa-miR-9-5p, hsa-miR-2115-5p) </span><span style="font-family:Verdana;">miRNAs </span><span style="font-family:Verdana;">which remarkably correlated with overall survival rate of BC were per</span><span style="font-family:Verdana;">formed by Cox regression analysis and miRNA signature risk score built. And then </span><span style="font-family:Verdana;">we performed the model of BC patients for three years survival risk, the</span><span style="font-family:Verdana;"> AUCs of ROC were 0.804, 0.667, and 0.739 in the training, test, and entire groups, respectively. miRNAs were differentially expressed in tumor-related </span><span style="font-family:Verdana;">biological processes and pathways by functional enrichment and</span><span style="font-family:Verdana;"> bioinformatic analysis. </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> The current study provided novel insights into the mi</span><span style="font-family:Verdana;">RNA-based mRNA network in BC. The nine miRNA and ten hub genes </span><span style="font-family:Verdana;">may be independent prognostic signatures for survival prediction in BC patients.</span></span>
