Rapid dissemination of antibiotic resistance genes among bacterial isolates is an increasing problem in China.Integron,a conserved DNA sequence,which is carried on episomal genetic structures,plays a very important ro...Rapid dissemination of antibiotic resistance genes among bacterial isolates is an increasing problem in China.Integron,a conserved DNA sequence,which is carried on episomal genetic structures,plays a very important role in development of antibiotic resistance.This systematic analysis was based on MEDLINE and EMBASE databases.We summarized the distribution and proportion of different types of gene cassette arrays of integrons(including class 1,2,3 and atypical class 1 integron) from clinical bacteria isolates in China.Fifty-six literatures were included in this study.Most of the strains were Gram-negative bacteria(94.1%,7,364/7,822) while only 5.9% strains were Grampositive bacteria.Class 1 integrons were detected in 54.2%(3956/7295) Gram-negative strains.aadA2 was the most popular gene cassette array detected from 60 Gram-positive bacteria while dfrA17-aadA5 were detected in 426 Gramnegative bacteria.This study identified 12 novel gene cassette arrays which have not been previously found in any species.All the novel gene cassette arrays were detected from Gram-negative bacteria.A regional characteristic of distribution of integrons was presented in this study.The results highlight a need for continuous surveillance of integrons and provide a guide for future research on integron-mediated bacteria resistance.展开更多
BACKGROUND Microvascular invasion(MVI)is an important prognostic factor affecting early recurrence and overall survival in hepatocellular carcinoma(HCC)patients after hepatectomy and liver transplantation,but it can b...BACKGROUND Microvascular invasion(MVI)is an important prognostic factor affecting early recurrence and overall survival in hepatocellular carcinoma(HCC)patients after hepatectomy and liver transplantation,but it can be determined only in surgical specimens.Accurate preoperative prediction of MVI is conducive to clinical decisions.AIM To develop and validate a preoperative prediction model for MVI in patients with HCC.METHODS Data from 454 patients with HCC who underwent hepatectomy at the First Affiliated Hospital of Nanjing Medical University between May 2016 and October 2019 were retrospectively collected.Then,the patients were nonrandomly split into a training cohort and a validation cohort.Logistic regression analysis was used to identify variables significantly associated with MVI that were then included in the nomogram.We evaluated the discrimination and calibration ability of the nomogram by using R software.RESULTS MVI was confirmed in 209(46.0%)patients by a pathological examination.Multivariate logistic regression analysis identified four risk factors independently associated with MVI:Tumor size[odds ratio(OR)=1.195;95%confidence interval(CI):1.107–1.290;P<0.001],number of tumors(OR=4.441;95%CI:2.112–9.341;P<0.001),neutrophils(OR=1.714;95%CI:1.036–2.836;P=0.036),and serumα-fetoprotein(20–400 ng/mL,OR=1.955;95%CI:1.055–3.624;P=0.033;>400 ng/mL,OR=3.476;95%CI:1.950–6.195;P<0.001).The concordance index was 0.79(95%CI:0.74–0.84)and 0.81(95%CI:0.74–0.89)in the training and validation cohorts,respectively.The calibration curves showed good agreement between the predicted risk by the nomogram and real outcomes.CONCLUSION We have developed and validated a preoperative prediction model for MVI in patients with HCC.The model could aid physicians in clinical treatment decision making.展开更多
Background:Inflammation is often linked with the progress and poor outcome of lung cancer.The understanding of the relationship between tumor-associated macrophages(TAMs) and lung cancer cells involves in the underlyi...Background:Inflammation is often linked with the progress and poor outcome of lung cancer.The understanding of the relationship between tumor-associated macrophages(TAMs) and lung cancer cells involves in the underlying mechanism of inflammatory cytokine production.Toll-like receptors(TLRs) are engaged in promoting the production of pro-inflammatory cytokines and play an important role in tumor immunology.Methods:To investigate the mechanisms by which TAMs influence the production of pro-inflammatory cytokines in lung cancer cells,we established an in vitro coculture system using TAMs and human nonsmall cell lung cancer(NSCLC) cell line SPC-A1.Levels of interleukin(IL)-1β,IL-6 and IL-8 in SPC-A1 were evaluated by RT-PCR and cytometric bead array assay after being cocultured with TAMs.Expression changes of TLRs and TLRs signaling pathway proteins in SPC-A1 were further confirmed by RT-PCR and western blot.The level changes of IL-1β,IL-6 and IL-8 in SPC-A1 were also detected after the stimulation of TLRs agonists.Results:We found that the phenotype markers of TAMs were highly expressed after stimulating human monocyte cell line THP-1 by phorbol-12-myristate-13-acetate(PMA).Higher mRNA and supernate secretion levels of IL-1β,IL-6 and IL-8 were detected in SPC-A1 after being cocultured with TAMs.We also found that TLR1,TLR6 and TLR7 were up-regulated in SPC-A1 in the coculture system with TAMs.Meanwhile,TLRs signaling pathway proteins were also significantly activated.Moreover,pre-treatment with agonist ligands for TLR1,TLR6 and TLR7 could dramatically promote inductions of IL-1β,IL-6 and IL-8.Conclusions:These findings demonstrated that TAMs may enhance IL-1β,IL-6 and IL-8 expressions via TLRs signaling pathway.We conclude that TAMs contribute to maintain the inflammation microenvironment and ultimately promote the development and progression of lung cancer.展开更多
Shigellosis causes diarrheal disease in humans in both developed and developing countries, and multi-drug resistance in Shigella is an emerging problem. Understanding changing resistance patterns is important in deter...Shigellosis causes diarrheal disease in humans in both developed and developing countries, and multi-drug resistance in Shigella is an emerging problem. Understanding changing resistance patterns is important in determining appropriate antibiotic treatments. This meta-analysis systematically evaluated aminoglycoside resist-ance in Shigella. A systematic review was constructed based on MEDLINE and EMBASE databases. Randomeffect models or fixed-effect models were used based on P value considering the possibility of heterogeneity between studies for meta-analysis. Data manipulation and statistical analyses were performed using software STATA 11.0. By means of meta-analysis, we found a lower resistance to three kinds of aminoglycosides in the Europe-America areas during the 12 year study period than that of the Asia-Africa areas. Kanamycin resistance was observed to be the most common drug resistance among Shigella isolates with a prevalence of 6.88% (95%CI: 6.36%-7.43%). Comparison of data from Europe-America and Asia-Africa areas revealed that Shigella flexneri resistance was greater than the resistance calculated for Shigella sonnei. Importantly,Shigella sonnei has played a significant role in aminoglycoside-resistance in recent years. Similarly, data showed that resistance to these drugs in children was higher than the corresponding data of adults. In conclusion, aminoglycoside-resistant Shigella is not an unusual phenomenon worldwide. Distribution in Shigella resistance differs sharply based on geographic areas, periods of time and subtypes. The results from the present study highlight the need for continuous surveillance of resistance and control of antibiotic usage.展开更多
Meigs’syndrome(MS),a rare complication of benign ovarian tumors,is easily misdiagnosed as ovarian cancer(OC).We retrospectively reviewed the clinical laboratory data of patients diagnosed with MS from 2009 to 2018.Se...Meigs’syndrome(MS),a rare complication of benign ovarian tumors,is easily misdiagnosed as ovarian cancer(OC).We retrospectively reviewed the clinical laboratory data of patients diagnosed with MS from 2009 to 2018.Serum carbohydrate antigen 125 and HE4 levels were higher in the MS group than in the ovarian thecoma-fibroma(OTF)and healthy control groups(all P<0.05).However,the serum HE4 levels were lower in the MS group than in the OC group(P<0.001).A routine blood test showed that the absolute counts and percentages of lymphocytes were significantly lower in the MS group than in the OTF and control groups(all P<0.05).However,these variables were higher in the MS group than in the OC group(both P<0.05).The neutrophil-to-lymphocyte ratio(NLR)was also significantly lower,whereas the lymphocyte-to-monocyte ratio was higher in the MS group than in the OC group(both P<0.05).The NLR,platelet-to-lymphocyte ratio,and systemic immune index were significantly higher in the MS group than in the OTF and control groups(all P<0.05).The hypoxia-inducible factor-1 mRNA levels were also significantly higher,whereas the glucose transporter 1,lactate dehydrogenase,and enolase 1 mRNA levels were lower in peripheral CD4+T cells obtained preoperatively in a patient with MS than those in patients with OTF,patients with OC,and controls(all P<0.05).The expression of these four glucose metabolism genes was preferentially restored to normal levels after the tumor resection of MS(P<0.001).These clinical laboratory features can be useful in improving the preoperative diagnostic accuracy of MS.展开更多
Regulatory T(Treg)cells comprise diverse subsets of immunosuppressive cells that play a pivotal role in regulating immune homeostasis and preventing autoimmunity.In cancers,Treg cells can suppress antitumor immune res...Regulatory T(Treg)cells comprise diverse subsets of immunosuppressive cells that play a pivotal role in regulating immune homeostasis and preventing autoimmunity.In cancers,Treg cells can suppress antitumor immune responses and support the establishment of an immunosuppressive tumor micro-environment,thus promoting immune evasion and cancer progression.1 Treg cells are increased or activated in the tumor microenvironment,which is associated with a poor clinical outcome.2 Although CD4^(+) Treg cells have been extensively studied,the lack of universal markers to distinguish CD8^(+) Treg cells from conventional CD8^(+)T cells means that the function of CD8^(+) Treg cells in cancer has not been fully characterized.Now,an increasing body of research has revealed that CD8^(+)Treg cells(CD8^(+)CD25^(+)Foxp3^(+),CD25^(+)CD122^(+)Foxp3^(+) and CD8^(+)CD28−)3–5 accumulate in the tumor microenvironment and suppress antitumor immunity(Fig.1).However,the influence of CD8^(+) Treg cells on tumor progression in ovarian cancer(OC)is less clear.Moreover,there are a limited number of studies describing the molecular signatures involved in the induction of CD8^(+) Treg cells.展开更多
基金funded by the National Natural Science Foundation of China(No.81000754 and No. 81471994)received a grant from the Key Laboratory for Laboratory Medicine of Jiangsu Province of China(No.XK201114)
文摘Rapid dissemination of antibiotic resistance genes among bacterial isolates is an increasing problem in China.Integron,a conserved DNA sequence,which is carried on episomal genetic structures,plays a very important role in development of antibiotic resistance.This systematic analysis was based on MEDLINE and EMBASE databases.We summarized the distribution and proportion of different types of gene cassette arrays of integrons(including class 1,2,3 and atypical class 1 integron) from clinical bacteria isolates in China.Fifty-six literatures were included in this study.Most of the strains were Gram-negative bacteria(94.1%,7,364/7,822) while only 5.9% strains were Grampositive bacteria.Class 1 integrons were detected in 54.2%(3956/7295) Gram-negative strains.aadA2 was the most popular gene cassette array detected from 60 Gram-positive bacteria while dfrA17-aadA5 were detected in 426 Gramnegative bacteria.This study identified 12 novel gene cassette arrays which have not been previously found in any species.All the novel gene cassette arrays were detected from Gram-negative bacteria.A regional characteristic of distribution of integrons was presented in this study.The results highlight a need for continuous surveillance of integrons and provide a guide for future research on integron-mediated bacteria resistance.
基金the National Natural Science Foundation of China,No.81672100the Key Laboratory for Laboratory Medicine of Jiangsu Province of China,No.ZDXKB2016005.
文摘BACKGROUND Microvascular invasion(MVI)is an important prognostic factor affecting early recurrence and overall survival in hepatocellular carcinoma(HCC)patients after hepatectomy and liver transplantation,but it can be determined only in surgical specimens.Accurate preoperative prediction of MVI is conducive to clinical decisions.AIM To develop and validate a preoperative prediction model for MVI in patients with HCC.METHODS Data from 454 patients with HCC who underwent hepatectomy at the First Affiliated Hospital of Nanjing Medical University between May 2016 and October 2019 were retrospectively collected.Then,the patients were nonrandomly split into a training cohort and a validation cohort.Logistic regression analysis was used to identify variables significantly associated with MVI that were then included in the nomogram.We evaluated the discrimination and calibration ability of the nomogram by using R software.RESULTS MVI was confirmed in 209(46.0%)patients by a pathological examination.Multivariate logistic regression analysis identified four risk factors independently associated with MVI:Tumor size[odds ratio(OR)=1.195;95%confidence interval(CI):1.107–1.290;P<0.001],number of tumors(OR=4.441;95%CI:2.112–9.341;P<0.001),neutrophils(OR=1.714;95%CI:1.036–2.836;P=0.036),and serumα-fetoprotein(20–400 ng/mL,OR=1.955;95%CI:1.055–3.624;P=0.033;>400 ng/mL,OR=3.476;95%CI:1.950–6.195;P<0.001).The concordance index was 0.79(95%CI:0.74–0.84)and 0.81(95%CI:0.74–0.89)in the training and validation cohorts,respectively.The calibration curves showed good agreement between the predicted risk by the nomogram and real outcomes.CONCLUSION We have developed and validated a preoperative prediction model for MVI in patients with HCC.The model could aid physicians in clinical treatment decision making.
基金the technical support from National Key Clinical Department of Laboratory Medicine of Jiangsu Province Hospitalsupported by National Natural Science Foundation of China(No. 81272324,81371894)+1 种基金Key Laboratory for Medicine of Jiangsu Province of China(No.XK201114)project funded by the Priority Academic Program Development ofJiangsu Higher Education Institutions
文摘Background:Inflammation is often linked with the progress and poor outcome of lung cancer.The understanding of the relationship between tumor-associated macrophages(TAMs) and lung cancer cells involves in the underlying mechanism of inflammatory cytokine production.Toll-like receptors(TLRs) are engaged in promoting the production of pro-inflammatory cytokines and play an important role in tumor immunology.Methods:To investigate the mechanisms by which TAMs influence the production of pro-inflammatory cytokines in lung cancer cells,we established an in vitro coculture system using TAMs and human nonsmall cell lung cancer(NSCLC) cell line SPC-A1.Levels of interleukin(IL)-1β,IL-6 and IL-8 in SPC-A1 were evaluated by RT-PCR and cytometric bead array assay after being cocultured with TAMs.Expression changes of TLRs and TLRs signaling pathway proteins in SPC-A1 were further confirmed by RT-PCR and western blot.The level changes of IL-1β,IL-6 and IL-8 in SPC-A1 were also detected after the stimulation of TLRs agonists.Results:We found that the phenotype markers of TAMs were highly expressed after stimulating human monocyte cell line THP-1 by phorbol-12-myristate-13-acetate(PMA).Higher mRNA and supernate secretion levels of IL-1β,IL-6 and IL-8 were detected in SPC-A1 after being cocultured with TAMs.We also found that TLR1,TLR6 and TLR7 were up-regulated in SPC-A1 in the coculture system with TAMs.Meanwhile,TLRs signaling pathway proteins were also significantly activated.Moreover,pre-treatment with agonist ligands for TLR1,TLR6 and TLR7 could dramatically promote inductions of IL-1β,IL-6 and IL-8.Conclusions:These findings demonstrated that TAMs may enhance IL-1β,IL-6 and IL-8 expressions via TLRs signaling pathway.We conclude that TAMs contribute to maintain the inflammation microenvironment and ultimately promote the development and progression of lung cancer.
基金funded by National Natural Science Foundation of China (No. 81000754)a grant from the Key Laboratory for Laboratory Medicine of Jiangsu Province of China (No. XK201114)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘Shigellosis causes diarrheal disease in humans in both developed and developing countries, and multi-drug resistance in Shigella is an emerging problem. Understanding changing resistance patterns is important in determining appropriate antibiotic treatments. This meta-analysis systematically evaluated aminoglycoside resist-ance in Shigella. A systematic review was constructed based on MEDLINE and EMBASE databases. Randomeffect models or fixed-effect models were used based on P value considering the possibility of heterogeneity between studies for meta-analysis. Data manipulation and statistical analyses were performed using software STATA 11.0. By means of meta-analysis, we found a lower resistance to three kinds of aminoglycosides in the Europe-America areas during the 12 year study period than that of the Asia-Africa areas. Kanamycin resistance was observed to be the most common drug resistance among Shigella isolates with a prevalence of 6.88% (95%CI: 6.36%-7.43%). Comparison of data from Europe-America and Asia-Africa areas revealed that Shigella flexneri resistance was greater than the resistance calculated for Shigella sonnei. Importantly,Shigella sonnei has played a significant role in aminoglycoside-resistance in recent years. Similarly, data showed that resistance to these drugs in children was higher than the corresponding data of adults. In conclusion, aminoglycoside-resistant Shigella is not an unusual phenomenon worldwide. Distribution in Shigella resistance differs sharply based on geographic areas, periods of time and subtypes. The results from the present study highlight the need for continuous surveillance of resistance and control of antibiotic usage.
基金supported by the National Natural Science Foundation of China(No.81772779)“Professionals from SixPronged Top-Talent Program”of Jiangsu Province(No.LGY2017068)+2 种基金“The Six Top Talent Project”of Jiangsu Province(No.2015-WSN-034)Medical Talent of Empowering Medicine through Science and Education Program of Jiangsu Province(No.ZDRCA2016003)Key Laboratory for Medicine of Jiangsu Province of China(No.ZDXKB2016005).
文摘Meigs’syndrome(MS),a rare complication of benign ovarian tumors,is easily misdiagnosed as ovarian cancer(OC).We retrospectively reviewed the clinical laboratory data of patients diagnosed with MS from 2009 to 2018.Serum carbohydrate antigen 125 and HE4 levels were higher in the MS group than in the ovarian thecoma-fibroma(OTF)and healthy control groups(all P<0.05).However,the serum HE4 levels were lower in the MS group than in the OC group(P<0.001).A routine blood test showed that the absolute counts and percentages of lymphocytes were significantly lower in the MS group than in the OTF and control groups(all P<0.05).However,these variables were higher in the MS group than in the OC group(both P<0.05).The neutrophil-to-lymphocyte ratio(NLR)was also significantly lower,whereas the lymphocyte-to-monocyte ratio was higher in the MS group than in the OC group(both P<0.05).The NLR,platelet-to-lymphocyte ratio,and systemic immune index were significantly higher in the MS group than in the OTF and control groups(all P<0.05).The hypoxia-inducible factor-1 mRNA levels were also significantly higher,whereas the glucose transporter 1,lactate dehydrogenase,and enolase 1 mRNA levels were lower in peripheral CD4+T cells obtained preoperatively in a patient with MS than those in patients with OTF,patients with OC,and controls(all P<0.05).The expression of these four glucose metabolism genes was preferentially restored to normal levels after the tumor resection of MS(P<0.001).These clinical laboratory features can be useful in improving the preoperative diagnostic accuracy of MS.
基金This study was supported by Natural Science Foundation of China(No.81772779)Jiangsu Province’sKey Provincial Talents Program(No.ZDRCA2016003)+1 种基金Key Laboratory for Medicine of Jiangsu Province of China(No.ZDXKB2016005)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Regulatory T(Treg)cells comprise diverse subsets of immunosuppressive cells that play a pivotal role in regulating immune homeostasis and preventing autoimmunity.In cancers,Treg cells can suppress antitumor immune responses and support the establishment of an immunosuppressive tumor micro-environment,thus promoting immune evasion and cancer progression.1 Treg cells are increased or activated in the tumor microenvironment,which is associated with a poor clinical outcome.2 Although CD4^(+) Treg cells have been extensively studied,the lack of universal markers to distinguish CD8^(+) Treg cells from conventional CD8^(+)T cells means that the function of CD8^(+) Treg cells in cancer has not been fully characterized.Now,an increasing body of research has revealed that CD8^(+)Treg cells(CD8^(+)CD25^(+)Foxp3^(+),CD25^(+)CD122^(+)Foxp3^(+) and CD8^(+)CD28−)3–5 accumulate in the tumor microenvironment and suppress antitumor immunity(Fig.1).However,the influence of CD8^(+) Treg cells on tumor progression in ovarian cancer(OC)is less clear.Moreover,there are a limited number of studies describing the molecular signatures involved in the induction of CD8^(+) Treg cells.
