Bile acids(BAs)are synthesized by the liver from cholesterol through several complementary pathways and aberrant cholesterol metabolism plays pivotal roles in the pathogeneses of cholesterol gallbladder polyps(CGP)and...Bile acids(BAs)are synthesized by the liver from cholesterol through several complementary pathways and aberrant cholesterol metabolism plays pivotal roles in the pathogeneses of cholesterol gallbladder polyps(CGP)and cholesterol gallstones(CGS).To date,there is neither systematic study on BAs profile of CGP or CGS,nor the relationship between them.To explore the metabolomics profile of plasma BAs in healthy volunteers,CGP and CGS patients,an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method was developed and validated for simultaneous determination of 42 free and conjugated BAs in human plasma.The developed method was sensitive and reproducible to be applied for the quantification of BAs in the investigation of plasma samples.The results show that,compared to healthy volunteers,CGP and CGS were both characterized by the significant decrease in plasma BAs pool size,furthermore CGP and CGS shared aberrant BAs metabolic characteristics.Chenodeoxycholic acid,glycochenodeoxycholic acid,l-muricholic acid,deoxycholic acid,and 7-ketolithocholic acid were shared potential markers of these two cholesterol gallbladder diseases.Subsequent analysis showed that clinical characteristics including cysteine,ornithine and body mass index might be closely related to metabolisms of certain BA modules.This work provides metabolomic information for the study of gallbladder diseases and analytical methodologies for clinical target analysis and efficacy evaluation related to BAs in medical institutions.展开更多
Objective:This study explored the timing of interventional treatment for acute intramural aortic hematoma(IMH)and the corresponding high-risk factors for its development into local aortic dissection(AD).Method:This re...Objective:This study explored the timing of interventional treatment for acute intramural aortic hematoma(IMH)and the corresponding high-risk factors for its development into local aortic dissection(AD).Method:This retrospective case study method examined clinical follow-up data of 42 patients with acute IMH between April 2013 and October 2016 from the First Affiliated Hospital of Xi?an Jiaotong University.SPSS 17.0 and PPMS1.5 were used to analyze follow-up data spanning 3–12 months(mean,7.5?3.7 months).Results:Patients were divided into the conversion group and the hematoma group according to whether they developed AD.Among them,16 patients(38.1%)developed AD and were treated with thoracic endovascular aortic repair(TEVAR).The remaining patients(61.89%)were treated conservatively.After 1 week,the mean aortic diameter of the conversion versus hematoma group was significantly widened.Hemodynamically unstable patients and those with hematoma to the abdominal aorta extension were more likely to develop AD.Patient outcomes after TEVAR were similar between groups.Conclusion:Our findings suggest that aortic isthmus diameter!3.0 cm,hematoma extending to the abdominal aorta,and hemodynamic instability are associated with AD development in acute IMH patents.TEVAR should be considered if hematoma thickening,calcification ingression,ulcer progression,or contrast enhancement within the intramural hematoma is noted beyond 2 weeks after IMH onset.展开更多
Background: The goal is to determine the incidence of symptomatic gastrointestinal (GI) injuries in acute coronary syndrome (ACS) patients receiving double antiplatelet therapy (DAPT). The risk factors for serious GI ...Background: The goal is to determine the incidence of symptomatic gastrointestinal (GI) injuries in acute coronary syndrome (ACS) patients receiving double antiplatelet therapy (DAPT). The risk factors for serious GI complications are also evaluated. Methods: 603 eligible patients from the Department of Cardiology at Zhongda Hospital between January 2014 and August 2015 were enrolled and the occurrence of GI injuries within one year assessed. The risk factors for serious GI complications were identified using cox regression analysis. Results: After one-year follow-up, 108 (17.9%) out of 603 patients developed symptomatic GI injuries: 22 (3.65%) with serious GI complications and 86 (14.2%) with GI symptoms. Drinking habit (95% CI: 1.512 - 8.796;P = 0.004) and previous peptic injury (95% CI: 2.307 - 18.080;P = 0.001) are independent predictors of serious GI complications, while proton pump inhibitor (PPI) was protective (95% CI: 0.120 - 0.699;P = 0.006) per cox regression analysis. Additionally, GI injuries of both serious GI complications and GI symptoms peaked in the first three months. Conclusions: Symptomatic GI injuries were relatively common in ACS patients with DAPT, especially in the first three months. Previous peptic injury and drinking habit were significant independent risk factors for serious GI complications, while PPI played a protective role in ACS with DAPT.展开更多
Introduction Congenital granular cell epulis(CGCE)is a rare,benign tumor that manifests on the mucosal surface of the alveolar ridge in newborns.It was initially described by Neumann in 1871 and has been referred to b...Introduction Congenital granular cell epulis(CGCE)is a rare,benign tumor that manifests on the mucosal surface of the alveolar ridge in newborns.It was initially described by Neumann in 1871 and has been referred to by various names such as congenital epulis,congenital epulis of the newborn,and congenital granular cell tumor.1 Documentation on larger tumors is limited and reported diameters vary.2 Diagnosis necessitates histological examination and immunohistochemical staining,typically revealing negative immunoreactivity for S-100 and cluster of differentiation 68(CD68).3,4 This article presents a case of CGCE with weakly positive S-100 and CD68 staining,alongside a relatively large size.Additionally,it conducts a literature review on diverse aspects,encompassing multidisciplinary prenatal diagnosis,antenatal management,choice of delivery mode during childbirth,and postnatal treatment,with the objective of augmenting clinicians’comprehension of the ailment.The study adhered to the guidelines of the Declaration of Helsinki and obtained informed consent from the patient and approval from the medical ethics committee of Chongqing Health Center for Women and Children.展开更多
As local regions in the tumor outstrip their oxygen supply,hypoxia can develop,affecting not only the cancer cells,but also other cells in the microenvironment,including cancer associated fibroblasts(CAFs).Hypoxia is ...As local regions in the tumor outstrip their oxygen supply,hypoxia can develop,affecting not only the cancer cells,but also other cells in the microenvironment,including cancer associated fibroblasts(CAFs).Hypoxia is also not necessarily stable over time,and can fluctuate or oscillate.Hypoxia Inducible Factor-1 is the master regulator of cellular response to hypoxia,and can also exhibit oscillations in its activity.To understand how stable,and fluctuating hypoxia influence breast CAFs,we measured changes in gene expression in CAFs in normoxia,hypoxia,and oscillatory hypoxia,as well as measured change in their capacity to resist,or assist breast cancer invasion.We show that hypoxia has a profound effect on breast CAFs causing activation of key pathways associated with fibroblast activation,but reduce myofibroblast activation and traction force generation.We also found that oscillatory hypoxia,while expectedly resulted in a“sub-hypoxic”response in gene expression,it resulted in specific activation of pathways associated with actin polymerization and actomyosin maturation.Using traction force microscopy,and a nanopatterned stromal invasion assay,we show that oscillatory hypoxia increases contractile force generation vs stable hypoxia,and increases heterogeneity in force generation response,while also additively enhancing invasibility of CAFs to MDA-MB-231 invasion.Our data show that stable and unstable hypoxia can regulate many mechnobiological characteristics of CAFs,and can contribute to transformation of CAFs to assist cancer dissemination and onset of metastasis.展开更多
Preeclampsia is characterized by new onset of hypertension and proteinuria after 20 weeks’gestation and is a leading cause of maternal and neonatal morbidity and mortality.The pathogenesis of preeclampsia is often as...Preeclampsia is characterized by new onset of hypertension and proteinuria after 20 weeks’gestation and is a leading cause of maternal and neonatal morbidity and mortality.The pathogenesis of preeclampsia is often associated with aberrant trophoblast function that leads to shallow placental implantation.However,the exact underlying mechanisms remain unclear.Placental LncZBTB39-1:2 expression level was investigated in 20 healthy placentae and 20 placentae with preeclampsia using qRT-PCR,and the metabolic profile of trophoblasts overexpressing LncZBTB39-1:2 in vitro was analysed using gas chromatography-mass spectrometry(GCeMS).In this study,we found that the expression of LncZBTB39-1:2 was significantly higher in preeclamptic placentae than in healthy placentae.Our metabolomics results have shown that tricarboxylic acid cycle intermediates and metabolites related to carbohydrate metabolism were decreased with the overexpression of LncZBTB39-1:2 in HTR8/SVneo cells.These findings were validated by detecting a lower level of intracellular ATP in HTR8/Vneo cells.Furthermore,the migration of HTR8/SVneo cells was compromised when cells were transfected with a plasmid encompassing LncZBTB39-1:2 overexpression.From these results,we conclude that abnormal levels of LncZBTB39-1:2 expression might lead to aberrant conditions in HTR-8/SVneo trophoblast cells.Aberrant conditions might be associated with dysregulated trophoblast migration and subsequent failure of uterine spiral artery remodelling,a pathogenesis recognised as a contributing factor in the aetiology of preeclampsia.展开更多
Water-soluble 2,6-helic[6]arene was used to construct supramolecular vesicles via host-vip interaction. Water-soluble 2,6-helic[6]arene was discovered to be high affinity host for suitable biomarkers. Supramolecular...Water-soluble 2,6-helic[6]arene was used to construct supramolecular vesicles via host-vip interaction. Water-soluble 2,6-helic[6]arene was discovered to be high affinity host for suitable biomarkers. Supramolecular vesicles were responsive to multiple stimuli types, including temperature, pH, Ca^2+, CO2 bubbling and biomarker displacement. Supramolecular vesicles were used to load and deliver anti-tumor drug doxorubicin to HeLa cells in vitro.展开更多
To the editor:The precise diagnosis and effective therapy of refractory diseases,such as neurodegenerative diseases,coronary heart diseases and cancers,is critical to increase the survival rate and improve the life qu...To the editor:The precise diagnosis and effective therapy of refractory diseases,such as neurodegenerative diseases,coronary heart diseases and cancers,is critical to increase the survival rate and improve the life quality of patients.Most of the conventional small molecular medicines are heavily associated with the limitations of poor solubility,low targeting efficiency,inducing drug resistance and systemic toxicity,promoting scientists to develop new strategies for overcoming these limitations.展开更多
Glutathione thiol-reactive pillar[6]arene(TWP6)is designed and synthesized as the first example of reducing agent-reactive host molecule.TWP6 shows high affinity binding towards suitable anti-tumor drugs and vips.Do...Glutathione thiol-reactive pillar[6]arene(TWP6)is designed and synthesized as the first example of reducing agent-reactive host molecule.TWP6 shows high affinity binding towards suitable anti-tumor drugs and vips.Doxorubicin-based acid-labile prodrugs and TWP6 are used to construct supramolecular vesicles,which are also loaded with camptothecin.The supramolecular vesicles loaded with two drugs demonstrate glutathione-and acid-responsive drug release as well as sequential release to both stimuli types.Supramolecular vesicles show combination therapeutic effect towards tumor cells in vitro.展开更多
Objective::This study focused on the prediction of preterm birth(PTB).It aimed to identify the transcriptomic signature essential for the occurrence of PTB and evaluate its predictive value in early,mid,and late pregn...Objective::This study focused on the prediction of preterm birth(PTB).It aimed to identify the transcriptomic signature essential for the occurrence of PTB and evaluate its predictive value in early,mid,and late pregnancy and in women with threatened preterm labor(TPTL).Methods::Blood transcriptome data of pregnant women were obtained from the Gene Expression Omnibus database.The activity of biological signatures was assessed using gene set enrichment analysis and single-sample gene set enrichment analysis.The correlation among molecules in the interleukin 6(IL6)signature and between IL6 signaling activity and the gestational week of delivery and latent period were evaluated by Pearson correlation analysis.The effects of molecules associated with the IL6 signature were fitted using logistic regression analysis;the predictive value of both the IL6 signature and IL6 alone were evaluated using receiver operating characteristic curves and pregnancy maintenance probability was assessed using Kaplan-Meier analysis.Differential analysis was performed using the DEseq2 and limma algorithms.Results::Circulatory IL6 signaling activity increased significantly in cases with preterm labor than in those with term pregnancies(normalized enrichment score(NES)=1.857,P=0.001).The IL6 signature(on which IL6 signaling is based)was subsequently considered as the candidate biomarker for PTB.The area under the curve(AUC)values for PTB prediction(using the IL6 signature)in early,mid,and late pregnancy were 0.810,0.695,and 0.779,respectively;these values were considerably higher than those for IL6 alone.In addition,the pregnancy curves of women with abnormal IL6 signature differed significantly from those with normal signature.In pregnant women who eventually had preterm deliveries,circulatory IL6 signaling activity was lower in early pregnancy(NES=-1.420,P=0.031)and higher than normal in mid(NES=1.671,P=0.002)and late pregnancy(NES=2.350,P<0.001).In women with TPTL,the AUC values for PTB prediction(or PTB within 7 days and 48 hours)using the IL6 signature were 0.761,0.829,and 0.836,respectively;the up-regulation of IL6 signaling activity and its correlation with the gestational week of delivery(r=-0.260,P=0.001)and latency period(r=-0.203,P=0.012)were more significant than in other women.Conclusion::Our findings suggest that the IL6 signature may predict PTB,even in early pregnancy(although the predictive power is relatively weak in mid pregnancy)and is particularly effective in symptomatic women.These findings may contribute to the development of an effective predictive and monitoring system for PTB,thereby reducing maternal and fetal risk.展开更多
To the Editor:With the extensive uptake of pertussis vaccine,morbidity and mortality related to pertussis have decreased significantly.The application of acellular vaccines(ACVs)occurred later in China than in develop...To the Editor:With the extensive uptake of pertussis vaccine,morbidity and mortality related to pertussis have decreased significantly.The application of acellular vaccines(ACVs)occurred later in China than in developed countries;correspondingly,the pertussis resurgence in China also began later.The latest global genotype dynamic prediction model cannot explain the B.pertussis genotype change trend in China.[1]Chinese B.pertussis strains gradually formed their own unique developmental branches.[2]Here,a phylogenetic tree of prevailing B.pertussis strains from three different regions of China was visualized by EvolView(http://www.evolgenius.info/evolview.html).A total of 199 isolated B.pertussis strains were used for the phylogenetic analysis.The B.para-pertussis strain isolated from Tianjin was used as the out-group,and Chinese strain(CS),which is widely used as a vaccine strain for ACV production in China,was used as the reference strain.In particular,we analyzed the multilocus sequence typing(MLST)and macrolide-resistance-conferring gene mutations.展开更多
Aconitum(Ranunculaceae)has a long-standing history in traditional Chinese medicine(TCM),where it has been widely used to treat conditions such as rheumatoid arthritis(RA),myocardial infarction,and heart failure.Howeve...Aconitum(Ranunculaceae)has a long-standing history in traditional Chinese medicine(TCM),where it has been widely used to treat conditions such as rheumatoid arthritis(RA),myocardial infarction,and heart failure.However,the potency of Aconitum alkaloids,the primary active components of Aconitum,also confers substantial toxicity.Therefore,assessing the efficacy and toxicity of these Aconitum alkaloids is crucial for ensuring clinical effectiveness and safety.Metabolomics,a quantitative method for analyzing low-molecular-weight metabolites involved in metabolic pathways,provides a comprehensive view of the metabolic state across multiple systems in vivo.This approach has become a vital investigative tool for facilitating the evaluation of their efficacy and toxicity,identifying potential sensitive biomarkers,and offering a promising avenue for elucidating the pharmacological and toxicological mechanisms underlying TCM.This review focuses on the applications of metabolomics in pharmacological and toxicological studies of Aconitum alkaloids in recent years and highlights the significant role of metabolomics in exploring compatibility detoxification and the mechanisms of TCM processing,aiming to identify more viable methods for characterizing toxic medicinal plants.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.:81920108033,and 82274223).
文摘Bile acids(BAs)are synthesized by the liver from cholesterol through several complementary pathways and aberrant cholesterol metabolism plays pivotal roles in the pathogeneses of cholesterol gallbladder polyps(CGP)and cholesterol gallstones(CGS).To date,there is neither systematic study on BAs profile of CGP or CGS,nor the relationship between them.To explore the metabolomics profile of plasma BAs in healthy volunteers,CGP and CGS patients,an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method was developed and validated for simultaneous determination of 42 free and conjugated BAs in human plasma.The developed method was sensitive and reproducible to be applied for the quantification of BAs in the investigation of plasma samples.The results show that,compared to healthy volunteers,CGP and CGS were both characterized by the significant decrease in plasma BAs pool size,furthermore CGP and CGS shared aberrant BAs metabolic characteristics.Chenodeoxycholic acid,glycochenodeoxycholic acid,l-muricholic acid,deoxycholic acid,and 7-ketolithocholic acid were shared potential markers of these two cholesterol gallbladder diseases.Subsequent analysis showed that clinical characteristics including cysteine,ornithine and body mass index might be closely related to metabolisms of certain BA modules.This work provides metabolomic information for the study of gallbladder diseases and analytical methodologies for clinical target analysis and efficacy evaluation related to BAs in medical institutions.
文摘Objective:This study explored the timing of interventional treatment for acute intramural aortic hematoma(IMH)and the corresponding high-risk factors for its development into local aortic dissection(AD).Method:This retrospective case study method examined clinical follow-up data of 42 patients with acute IMH between April 2013 and October 2016 from the First Affiliated Hospital of Xi?an Jiaotong University.SPSS 17.0 and PPMS1.5 were used to analyze follow-up data spanning 3–12 months(mean,7.5?3.7 months).Results:Patients were divided into the conversion group and the hematoma group according to whether they developed AD.Among them,16 patients(38.1%)developed AD and were treated with thoracic endovascular aortic repair(TEVAR).The remaining patients(61.89%)were treated conservatively.After 1 week,the mean aortic diameter of the conversion versus hematoma group was significantly widened.Hemodynamically unstable patients and those with hematoma to the abdominal aorta extension were more likely to develop AD.Patient outcomes after TEVAR were similar between groups.Conclusion:Our findings suggest that aortic isthmus diameter!3.0 cm,hematoma extending to the abdominal aorta,and hemodynamic instability are associated with AD development in acute IMH patents.TEVAR should be considered if hematoma thickening,calcification ingression,ulcer progression,or contrast enhancement within the intramural hematoma is noted beyond 2 weeks after IMH onset.
文摘Background: The goal is to determine the incidence of symptomatic gastrointestinal (GI) injuries in acute coronary syndrome (ACS) patients receiving double antiplatelet therapy (DAPT). The risk factors for serious GI complications are also evaluated. Methods: 603 eligible patients from the Department of Cardiology at Zhongda Hospital between January 2014 and August 2015 were enrolled and the occurrence of GI injuries within one year assessed. The risk factors for serious GI complications were identified using cox regression analysis. Results: After one-year follow-up, 108 (17.9%) out of 603 patients developed symptomatic GI injuries: 22 (3.65%) with serious GI complications and 86 (14.2%) with GI symptoms. Drinking habit (95% CI: 1.512 - 8.796;P = 0.004) and previous peptic injury (95% CI: 2.307 - 18.080;P = 0.001) are independent predictors of serious GI complications, while proton pump inhibitor (PPI) was protective (95% CI: 0.120 - 0.699;P = 0.006) per cox regression analysis. Additionally, GI injuries of both serious GI complications and GI symptoms peaked in the first three months. Conclusions: Symptomatic GI injuries were relatively common in ACS patients with DAPT, especially in the first three months. Previous peptic injury and drinking habit were significant independent risk factors for serious GI complications, while PPI played a protective role in ACS with DAPT.
基金the National Key Clinical Speciality Construction Project(Obstetrics and Gynecology),the Chongqing Science and Technology Commission(CSTB2022TIAD-KPX0171).
文摘Introduction Congenital granular cell epulis(CGCE)is a rare,benign tumor that manifests on the mucosal surface of the alveolar ridge in newborns.It was initially described by Neumann in 1871 and has been referred to by various names such as congenital epulis,congenital epulis of the newborn,and congenital granular cell tumor.1 Documentation on larger tumors is limited and reported diameters vary.2 Diagnosis necessitates histological examination and immunohistochemical staining,typically revealing negative immunoreactivity for S-100 and cluster of differentiation 68(CD68).3,4 This article presents a case of CGCE with weakly positive S-100 and CD68 staining,alongside a relatively large size.Additionally,it conducts a literature review on diverse aspects,encompassing multidisciplinary prenatal diagnosis,antenatal management,choice of delivery mode during childbirth,and postnatal treatment,with the objective of augmenting clinicians’comprehension of the ailment.The study adhered to the guidelines of the Declaration of Helsinki and obtained informed consent from the patient and approval from the medical ethics committee of Chongqing Health Center for Women and Children.
基金National Cancer Institute R37CA248161 for funding the research presented in the manuscript。
文摘As local regions in the tumor outstrip their oxygen supply,hypoxia can develop,affecting not only the cancer cells,but also other cells in the microenvironment,including cancer associated fibroblasts(CAFs).Hypoxia is also not necessarily stable over time,and can fluctuate or oscillate.Hypoxia Inducible Factor-1 is the master regulator of cellular response to hypoxia,and can also exhibit oscillations in its activity.To understand how stable,and fluctuating hypoxia influence breast CAFs,we measured changes in gene expression in CAFs in normoxia,hypoxia,and oscillatory hypoxia,as well as measured change in their capacity to resist,or assist breast cancer invasion.We show that hypoxia has a profound effect on breast CAFs causing activation of key pathways associated with fibroblast activation,but reduce myofibroblast activation and traction force generation.We also found that oscillatory hypoxia,while expectedly resulted in a“sub-hypoxic”response in gene expression,it resulted in specific activation of pathways associated with actin polymerization and actomyosin maturation.Using traction force microscopy,and a nanopatterned stromal invasion assay,we show that oscillatory hypoxia increases contractile force generation vs stable hypoxia,and increases heterogeneity in force generation response,while also additively enhancing invasibility of CAFs to MDA-MB-231 invasion.Our data show that stable and unstable hypoxia can regulate many mechnobiological characteristics of CAFs,and can contribute to transformation of CAFs to assist cancer dissemination and onset of metastasis.
基金supported by the Southwest University of Science and Technology of the Startup Foundation for Doctors (No.16ZX7139)the Longshan Talent Program (No.18LZX675)。
基金financed by the 111 Project(Yuwaizhuan(2016)32),China.
文摘Preeclampsia is characterized by new onset of hypertension and proteinuria after 20 weeks’gestation and is a leading cause of maternal and neonatal morbidity and mortality.The pathogenesis of preeclampsia is often associated with aberrant trophoblast function that leads to shallow placental implantation.However,the exact underlying mechanisms remain unclear.Placental LncZBTB39-1:2 expression level was investigated in 20 healthy placentae and 20 placentae with preeclampsia using qRT-PCR,and the metabolic profile of trophoblasts overexpressing LncZBTB39-1:2 in vitro was analysed using gas chromatography-mass spectrometry(GCeMS).In this study,we found that the expression of LncZBTB39-1:2 was significantly higher in preeclamptic placentae than in healthy placentae.Our metabolomics results have shown that tricarboxylic acid cycle intermediates and metabolites related to carbohydrate metabolism were decreased with the overexpression of LncZBTB39-1:2 in HTR8/SVneo cells.These findings were validated by detecting a lower level of intracellular ATP in HTR8/Vneo cells.Furthermore,the migration of HTR8/SVneo cells was compromised when cells were transfected with a plasmid encompassing LncZBTB39-1:2 overexpression.From these results,we conclude that abnormal levels of LncZBTB39-1:2 expression might lead to aberrant conditions in HTR-8/SVneo trophoblast cells.Aberrant conditions might be associated with dysregulated trophoblast migration and subsequent failure of uterine spiral artery remodelling,a pathogenesis recognised as a contributing factor in the aetiology of preeclampsia.
基金the National Natural Science Foundation of China (21672042) for financial support.
文摘Water-soluble 2,6-helic[6]arene was used to construct supramolecular vesicles via host-vip interaction. Water-soluble 2,6-helic[6]arene was discovered to be high affinity host for suitable biomarkers. Supramolecular vesicles were responsive to multiple stimuli types, including temperature, pH, Ca^2+, CO2 bubbling and biomarker displacement. Supramolecular vesicles were used to load and deliver anti-tumor drug doxorubicin to HeLa cells in vitro.
基金supported by the National Natural Science Foundation of China(32071374 and 81761148029)the Program of Shanghai Academic Research Leader under the Science and Technology Innovation Action Plan(21XD1422100,China)+2 种基金Leading Talent of“Ten Thousand Plan”-National High-Level Talents Special Support Plan,the One Belt and One Road International Cooperation Project from the Key Research and Development Program of Zhejiang Province(2019C04024,China)the Zhejiang Provincial Natural Science Foundation of China(LR22C100001,China)the innovative research team of highlevel local universities in Shanghai(SHSMU-ZDCX20210900,China).
文摘To the editor:The precise diagnosis and effective therapy of refractory diseases,such as neurodegenerative diseases,coronary heart diseases and cancers,is critical to increase the survival rate and improve the life quality of patients.Most of the conventional small molecular medicines are heavily associated with the limitations of poor solubility,low targeting efficiency,inducing drug resistance and systemic toxicity,promoting scientists to develop new strategies for overcoming these limitations.
基金National Natural Science Foundation of China(Nos.21921003 and 21672042)Zhengzhou University for financial support。
文摘Glutathione thiol-reactive pillar[6]arene(TWP6)is designed and synthesized as the first example of reducing agent-reactive host molecule.TWP6 shows high affinity binding towards suitable anti-tumor drugs and vips.Doxorubicin-based acid-labile prodrugs and TWP6 are used to construct supramolecular vesicles,which are also loaded with camptothecin.The supramolecular vesicles loaded with two drugs demonstrate glutathione-and acid-responsive drug release as well as sequential release to both stimuli types.Supramolecular vesicles show combination therapeutic effect towards tumor cells in vitro.
基金The study was supported by grants from the Chongqing Municipal Health Commission and the Chongqing Science and Technology Commission(no.2023GGXM005)the Science and Technology Department of Sichuan Province(no.2020YFQ0006)+2 种基金the Chongqing Science and Technology Commission(no.CSTB2022TIAD-KPX0166)the Chongqing Science and Technology Commission(no.cstc2020jcyj-msxmX0561)the National Key Clinical Specialty Construction Project(Obstetrics and Gynecology).
文摘Objective::This study focused on the prediction of preterm birth(PTB).It aimed to identify the transcriptomic signature essential for the occurrence of PTB and evaluate its predictive value in early,mid,and late pregnancy and in women with threatened preterm labor(TPTL).Methods::Blood transcriptome data of pregnant women were obtained from the Gene Expression Omnibus database.The activity of biological signatures was assessed using gene set enrichment analysis and single-sample gene set enrichment analysis.The correlation among molecules in the interleukin 6(IL6)signature and between IL6 signaling activity and the gestational week of delivery and latent period were evaluated by Pearson correlation analysis.The effects of molecules associated with the IL6 signature were fitted using logistic regression analysis;the predictive value of both the IL6 signature and IL6 alone were evaluated using receiver operating characteristic curves and pregnancy maintenance probability was assessed using Kaplan-Meier analysis.Differential analysis was performed using the DEseq2 and limma algorithms.Results::Circulatory IL6 signaling activity increased significantly in cases with preterm labor than in those with term pregnancies(normalized enrichment score(NES)=1.857,P=0.001).The IL6 signature(on which IL6 signaling is based)was subsequently considered as the candidate biomarker for PTB.The area under the curve(AUC)values for PTB prediction(using the IL6 signature)in early,mid,and late pregnancy were 0.810,0.695,and 0.779,respectively;these values were considerably higher than those for IL6 alone.In addition,the pregnancy curves of women with abnormal IL6 signature differed significantly from those with normal signature.In pregnant women who eventually had preterm deliveries,circulatory IL6 signaling activity was lower in early pregnancy(NES=-1.420,P=0.031)and higher than normal in mid(NES=1.671,P=0.002)and late pregnancy(NES=2.350,P<0.001).In women with TPTL,the AUC values for PTB prediction(or PTB within 7 days and 48 hours)using the IL6 signature were 0.761,0.829,and 0.836,respectively;the up-regulation of IL6 signaling activity and its correlation with the gestational week of delivery(r=-0.260,P=0.001)and latency period(r=-0.203,P=0.012)were more significant than in other women.Conclusion::Our findings suggest that the IL6 signature may predict PTB,even in early pregnancy(although the predictive power is relatively weak in mid pregnancy)and is particularly effective in symptomatic women.These findings may contribute to the development of an effective predictive and monitoring system for PTB,thereby reducing maternal and fetal risk.
基金Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJYXZDXK059B)
文摘To the Editor:With the extensive uptake of pertussis vaccine,morbidity and mortality related to pertussis have decreased significantly.The application of acellular vaccines(ACVs)occurred later in China than in developed countries;correspondingly,the pertussis resurgence in China also began later.The latest global genotype dynamic prediction model cannot explain the B.pertussis genotype change trend in China.[1]Chinese B.pertussis strains gradually formed their own unique developmental branches.[2]Here,a phylogenetic tree of prevailing B.pertussis strains from three different regions of China was visualized by EvolView(http://www.evolgenius.info/evolview.html).A total of 199 isolated B.pertussis strains were used for the phylogenetic analysis.The B.para-pertussis strain isolated from Tianjin was used as the out-group,and Chinese strain(CS),which is widely used as a vaccine strain for ACV production in China,was used as the reference strain.In particular,we analyzed the multilocus sequence typing(MLST)and macrolide-resistance-conferring gene mutations.
基金supported by the National Natural Science Foundation of China (No.82274223)。
文摘Aconitum(Ranunculaceae)has a long-standing history in traditional Chinese medicine(TCM),where it has been widely used to treat conditions such as rheumatoid arthritis(RA),myocardial infarction,and heart failure.However,the potency of Aconitum alkaloids,the primary active components of Aconitum,also confers substantial toxicity.Therefore,assessing the efficacy and toxicity of these Aconitum alkaloids is crucial for ensuring clinical effectiveness and safety.Metabolomics,a quantitative method for analyzing low-molecular-weight metabolites involved in metabolic pathways,provides a comprehensive view of the metabolic state across multiple systems in vivo.This approach has become a vital investigative tool for facilitating the evaluation of their efficacy and toxicity,identifying potential sensitive biomarkers,and offering a promising avenue for elucidating the pharmacological and toxicological mechanisms underlying TCM.This review focuses on the applications of metabolomics in pharmacological and toxicological studies of Aconitum alkaloids in recent years and highlights the significant role of metabolomics in exploring compatibility detoxification and the mechanisms of TCM processing,aiming to identify more viable methods for characterizing toxic medicinal plants.
