Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a ...Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a C-C chemokine receptor type 5 antagonist,has been viewed as a new therapeutic strategy for many neuroinflammatory diseases.We studied the effect of maraviroc on TBI-induced neuroinflammation.A moderate-TBI mouse model was subjected to a controlled cortical impact device.Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days.Western blot,immunohistochemistry,and TUNEL(terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI.Our results suggest that maraviroc administration reduced NACHT,LRR,and PYD domains-containing protein 3 inflammasome activation,modulated microglial polarization from M1 to M2,decreased neutrophil and macrophage infiltration,and inhibited the release of inflammatory factors after TBI.Moreover,maraviroc treatment decreased the activation of neurotoxic reactive astrocytes,which,in turn,exacerbated neuronal cell death.Additionally,we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score,rotarod test,Morris water maze test,and lesion volume measurements.In summary,our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI,and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI.展开更多
Objective To investigate the ultrasonic detection probability, type, prenatal diagnosis, and outcome of congenital cystic adenomatoid malformation of lung (CCAM). Methods In this retrospective study, all 12 cases whic...Objective To investigate the ultrasonic detection probability, type, prenatal diagnosis, and outcome of congenital cystic adenomatoid malformation of lung (CCAM). Methods In this retrospective study, all 12 cases which were diagnosed with suspected prenatal CCAM over the period in the hospital were analyzed. Information on diagnosis time, types and progression of the lesions during pregnancy, the additional abnormalities, and the outcome of pregnancies were recorded. Results The positive rate of ultrasonic detection of CCAM was about 1.01‰ (1/11 124) before 28 gestation weeks. There were 1 case of type I (8%), 2 cases of type II (17%) and 9 cases of type III (75%). Nine pregnancies were terminated and 2 cases were confirmed by pathology. Three neonates were alive and without any symptom now. Conclusions Type III is the major type. Ultrasound examination during 20-28 weeks and following up, prenatal consultation, chromosome examination of fetus, delivery with a pediatrician standing by, and all suspected neonates being investigated are recommended.展开更多
In this paper,we investigate the effects of lattice strain on the electrical and magnetotransport properties of La0.7Sr0.3MnO3(LSMO)films by changing film thickness and substrate.For electrical properties,a resistivit...In this paper,we investigate the effects of lattice strain on the electrical and magnetotransport properties of La0.7Sr0.3MnO3(LSMO)films by changing film thickness and substrate.For electrical properties,a resistivity upturn emerges in LSMO films,i.e.,LSMO/STO and LSMO/LSAT with small lattice strain at a low temperature,which originates from the weak localization effect.Increasing film thickness weakens the weak localization effect,resulting in the disappearance of resistivity upturn.While in LSMO films with a large lattice strain(i.e.,LSMO/LAO),an unexpected semiconductor behavior is observed due to the linear defects.For magnetotransport properties,an anomalous in-plane magnetoresistance peak(pMR)occurs at low temperatures in LSMO films with small lattice strain,which is caused by two-dimensional electron gas(2DEG).Increasing film thickness suppresses the 2DEG,which weakens the pMR.Besides,it is found that the film orientation has no influence on the formation of 2DEG.While in LSMO/LAO films,the 2DEG cannot form due to the existence of linear defects.This work can provide an efficient way to regulate the film transport properties.展开更多
Objective:Ultrasound determination of chorionicity is poor in early pregnancy in China.In an effort to increase the accuracy rate of prompt chorionicity determination,clinical training was provided to primary care phy...Objective:Ultrasound determination of chorionicity is poor in early pregnancy in China.In an effort to increase the accuracy rate of prompt chorionicity determination,clinical training was provided to primary care physicians.This study assesses the effects of implementing clinical guidelines on chorionicity determination.Methods:A multi-centered cohort study was conducted between January 2014 and June 2017 in 12 hospitals without fetal medicine centers.In 2014,the obstetricians and ultrasound physicians were trained in clinical practice and ultrasound examination relating to chorionicity determination.Linear and binary regression analyses were conducted to identify the effects of introducing the new protocols,including the diagnosis rate of chorionicty and perinatal outcomes,taking the data from 2014 as a baseline.Pregnancy outcomes were additionally adjusted for maternal age.Results:During the period of this study,3,599 twin pregnancies from 12 centers were enrolled,and a total of 2,998 twin pregnancies were extracted.The rate of overall chorionicity determination,including antenatal and postpartum diagnosis,increased successively from 49.5% in 2014 to 93.5% in 2017(P<0.0001).The rate of ultrasonic chorionicity diagnosis before 14 weeks increased from 25.2% in 2014 to 65.0% in 2017(P<0.0001).These changes were associated with decreasing incidence of preterm birth,a lower risk of stillbirth,whether for one(P=0.0456 in 2016)or two fetuses(P=0.0470 in 2016;P=0.0042 in 2017)and a decreased rate of admission to neonatal intensive care unit(43.0% in 2014,37.4% in 2017;P=0.0032).Conclusions:The implementation of a clinical practice guideline improved both overall and early chorionicity determinations.Regular training workshops of antenatal care are recommended to further promote capability in clinical diagnosis and treatment.展开更多
Objective::The role of Vitamin D-binding protein(DBP)in preeclampsia(PE)pathogenesis is unknown.In this study,we compared the expression of DBP in the placentas of PE patients with the placentas of normotensive pregna...Objective::The role of Vitamin D-binding protein(DBP)in preeclampsia(PE)pathogenesis is unknown.In this study,we compared the expression of DBP in the placentas of PE patients with the placentas of normotensive pregnant women with placenta previa controls,and aimed to explore the effect of DBP on endothelial cells(ECs)and the underlying mechanism.Methods::DBP expression in placental tissues collected from PE patients and controls was evaluated by immunohistochemistry.The downregulation and upregulation of DBP expression in HTR-8/SVneo cells were examined using DBP-targeting small interfering RNA(siRNA)and DBP-expression vector,respectively.The conditioned media of these DBP-overexpressing and DBP-siRNA HTR-8/SVneo cells were collected and added to human umbilical vein EC(HUVEC)cultures.Angiogenic effects on HUVECs were assessed by tube formation assays,and the proliferation and migration of HUVECs were examined using the Real-Time Cell Analyzer.The expression of vascular endothelial growth factor(VEGF)and VEGF receptor(VEGFR)-2,as well as the phosphorylation of different residues of VEGFR-2 in HUVECs,were determined by western blotting.Results::DBP expression was significantly increased in the placental tissues collected from PE patients.The conditioned medium of DBP-overexpressing HTR-8/SVneo cells potently inhibited tube formation by HUVECs,in addition to their proliferation and migration.Furthermore,treatment of HUVECs with the conditioned medium of DBP-overexpressing HTR-8/SVneo cells decreased the phosphorylation of VEGFR-2 at tyrosine 996,whereas the treatment of these cells with the conditioned medium of DBP-siRNA HTR-8/SVneo cells increased the phosphorylation of VEGFR-2 at tyrosine 951,996,and 1,175.Conclusions::The expression of DBP is increased in the placentas of PE patients.DBP plays potential roles in endothelial dysfunction,which contributes to PE development,by inhibiting tyrosine phosphorylation of VEGFR-2 in ECs.展开更多
Objective:Long non-coding RNAs(lncRNAs)are implicated in multiple pathophysiological processes in placenta-related disorders;however,their expression and function in late-onset pre-eclampsia(LOPE)remain unclear.This s...Objective:Long non-coding RNAs(lncRNAs)are implicated in multiple pathophysiological processes in placenta-related disorders;however,their expression and function in late-onset pre-eclampsia(LOPE)remain unclear.This study aimed to investigate the expression of lncRNAs in LOPE,construct a competing endogenous RNA(ceRNA)network,and identify the pathways associated with LOPE pathogenesis.Methods:We performed lncRNA and mRNAs microarray profiling to identify the differential expression profiles of lncRNAs and mRNAs in LOPE compared to those in normal pregnancy.Quantitative reverse transcription polymerase chain reaction(qRT-PCR)was performed to validate differentially expressed genes.Subsequently,we generated an interaction network between lncRNAs,(micro-RNAs)miRNAs,and mRNAs based on the Pearson’s correlation coefficient between lncRNAs and mRNAs.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed to understand the functional significance of differentially expressed lncRNAs(DElncRNAs)in LOPE.Results:We identified 29 DElncRNAs(25 upregulated and four downregulated)and 212 differentially expressed mRNAs(DEmRNAs;203 upregulated and nine downregulated)in LOPE placentas.Within them,six lncRNAs and four mRNAs were verified by qRT-PCR.GO and KEGG analyses revealed the potential pathways affected by these mRNAs,such as positive regulation of leukocyte chemotaxis,chemokine signaling pathway,and response to hypoxia.Finally,we constructed a ceRNA network including three DElncRNAs and 124 DEmRNAs,whose competing interactions may be mediated by 17 miRNAs.Two DElncRNAs,ENST00000515376 and ENST00000520544,were found to be hub genes,as they interacted with most miRNAs and mRNAs.ENST00000515376 is most likely related to the metabolic process of arachidonic acid,whereas ENST00000520544 is more likely related to the coagulation system,such as the regulation of blood coagulation and platelet degranulation.Conclusion:Differential expression profile of lncRNAs and the lncRNA-miRNA-mRNA network in LOPE provide potential therapeutic targets for this disease.展开更多
Background:China’s two-child policy has led to a trend of aging in pregnancy which was associated with adverse outcomes.This study aimed to identify the clinically cutoff maternal age for adverse obstetric outcomes i...Background:China’s two-child policy has led to a trend of aging in pregnancy which was associated with adverse outcomes.This study aimed to identify the clinically cutoff maternal age for adverse obstetric outcomes in China.Methods:This secondary analysis of a multicenter retrospective cohort study included data of childbearing women from 39 hospitals collected in urban China during 2011 to 2012.Logistic regression was used to assess the adjusted odds ratios(aOR)of adverse outcomes in different age groups in comparison to women aged 20 to 24 years.The adjustments included the location of the hospital,educational level,and residence status.Clinically cutoff age was defined as the age above which the aOR continuously become both statistically(P<0.05)and clinically(aOR>2)significant.Results:Overall,108,059 women were recruited.In primiparae,clinically cutoff maternal ages for gestational diabetes(aOR:2.136,95%confidence interval[CI]:1.856-2.458,P<0.001),placenta previa(aOR:2.400,95%CI:1.863-3.090,P<0.001),cesarean section(aOR:2.511,95%CI:2.341-2.694,P<0.001),hypertensive disorder(aOR:2.122,95%CI:1.753-2.569,P<0.001),post-partum hemorrhage(aOR:2.129,95%CI:1.334-3.397,P<0.001),and low birth weight(aOR:2.174,95%CI:1.615-2.927,P<0.001)were 27,31,33,37,41,and 41 years,respectively.In multiparae,clinically cutoff ages for gestational diabetes(aOR:2.977,95%CI:1.808-4.904,P<0.001),hypertensive disorder(aOR:2.555,95%CI:1.836-3.554,P<0.001),cesarean section(aOR:2.224,95%CI:1.952-2.534,P<0.001),post-partum hemorrhage(aOR:2.140,95%CI:1.472-3.110,P<0.001),placenta previa(aOR:2.272,95%CI:1.375-3.756,P<0.001),macrosomia(aOR:2.215,95%CI:1.552-3.161,P<0.001),and neonatal asphyxia(aOR:2.132,95%CI:1.461-3.110,P<0.001)were 29,31,33,35,35,41,and 41 years,respectively.Conclusions:Early cutoff ages for gestational diabetes and cesarean section highlight a reasonable childbearing age in urban China.The various optimized cutoff ages for different adverse pregnancy outcomes should be carefully considered in childbearing women.展开更多
Objective:The aim of the study is to investigate the relationship between antenatal depression and adverse perinatal outcomes.Methods:This prospective cohort study enrolled pregnant women between gestational ages of 1...Objective:The aim of the study is to investigate the relationship between antenatal depression and adverse perinatal outcomes.Methods:This prospective cohort study enrolled pregnant women between gestational ages of 12-20 weeks to complete the Chinese version of the Zung Self-Rating Depression Scale(SDS)and followed them for delivery from September 2015 to September 2016.Participants were classified into mild,moderate,and severe depression groups according to the SDS scores.Logistic regression was performed to assess the association between antenatal depression and perinatal outcomes including preterm birth(PTB),cesarean section use,hypertension disorders,gestational diabetes,and thyroid diseases during pregnancy.An age-stratified analysis was performed.Results:A total of 4,663 pregnant women were analyzed.As a result,13.8%,1.7%,and 0.2%of women were classified as mild,moderate,and severe depression,respectively.Severely depressed mothers were at higher risk for PTB(adjusted odds ratio[OR]=11.31,95%confidence interval[CI]2.13-60.03),especially spontaneous PTB.Moderate-depressed women were at higher risk for hyperthyroidism during pregnancy(adjusted OR=3.67,95%CI 1.10-12.27),while women with mild depression tended to choose cesarean sections(OR=1.24,95%CI=1.04-1.49).Age-stratified analysis indicated an elevated risk of adverse outcomes associated with depression in women aged<25 years,but the association was not significant.Conclusions:Antenatal depression was associated with PTB,hyperthyroidism,and cesarean use.Studies with large sample sizes should verify the relationship between PTB and antenatal depression to avoid casual events.展开更多
Objective: To characterize and compare the microbiome signature in the maternal, intrauterine, and fetal environments and the associated bacterial species in women who experienced preterm birth and term birth.Methods:...Objective: To characterize and compare the microbiome signature in the maternal, intrauterine, and fetal environments and the associated bacterial species in women who experienced preterm birth and term birth.Methods: A total of 140 women with singleton pregnancies were enrolled in this study. Among them, 31 experienced spontaneous preterm delivery (gestational age < 37 weeks), and 28 of them experienced vaginal delivery at term. Maternal peripheral blood, saliva, and vaginal discharge samples and fetal membrane, amniotic fluid, and cord blood samples were collected immediately after delivery under sterile conditions. DNA was isolated from the fetal membrane and umbilical cord blood samples, and the V3-V4 region of the bacterial 16S rRNA gene was sequenced. The sequence data were quality-filtered, chimera-checked, and organized into operational taxonomic units (OTUs) based on phylogeny. Principal coordinate analysis of beta diversity measures was used for visualization. The linear discriminant analysis effect size (LEfSe) algorithm and Wilcoxon test were used to differentiate the microbiomes found in the fetal membranes and cord blood in the cases of preterm birth.Results: OTU analysis based on the 16S rRNA gene showed similar microbiomes in the maternal peripheral blood, amniotic fluid, fetal membranes, and cord blood. However, the LEfSe algorithm revealed significantly different bacterial compositions in the fetal environment between the preterm and term groups, with some of the bacterial species originating from the maternal peripheral blood or saliva.Conclusions: The bacteria in the intrauterine and fetal environments may originate from other body sites through hematogenous transmission, and may cause the occurrence of preterm birth.展开更多
基金supported by grants from the National Natural Science Foundation of China, Nos. 81930031 (to JNZ), 81720108015 (to JNZ), 81901525 (to SZ), 82101440 (to DDS), 81801234 (to YZ) and 82071389 (to GLY)the Natural Science Foundation of Tianjin, Nos. 20JCQNJC01270 (to JWW), 20JCQNJC00460 (to GLY), 18JCQNJC81000 (to HTR)+4 种基金Scientific Research Project of Tianjin Education Commission (Natural Science), No. 2018KJ052 (to ZWZ)Tianjin Health and Health Committee Science and Technology Project, No. QN20015 (to JWW)the Science & Technology Development Fund of Tianjin Education Commission for Higher Education, No. 2016YD02 (to YW)Tianjin Key Science and Technology Projects of Innovative Drugs and Medical Devices, No. 19ZXYXSY00070 (to YW)the Clinical Research Fundation of Tianjin Medical University, No. 2018kylc002 (to YW)
文摘Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a C-C chemokine receptor type 5 antagonist,has been viewed as a new therapeutic strategy for many neuroinflammatory diseases.We studied the effect of maraviroc on TBI-induced neuroinflammation.A moderate-TBI mouse model was subjected to a controlled cortical impact device.Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days.Western blot,immunohistochemistry,and TUNEL(terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI.Our results suggest that maraviroc administration reduced NACHT,LRR,and PYD domains-containing protein 3 inflammasome activation,modulated microglial polarization from M1 to M2,decreased neutrophil and macrophage infiltration,and inhibited the release of inflammatory factors after TBI.Moreover,maraviroc treatment decreased the activation of neurotoxic reactive astrocytes,which,in turn,exacerbated neuronal cell death.Additionally,we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score,rotarod test,Morris water maze test,and lesion volume measurements.In summary,our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI,and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI.
基金This study is supported by 2004-2006 important clinic studies of medical institutions belonging to the Health Care Ministry of China
文摘Objective To investigate the ultrasonic detection probability, type, prenatal diagnosis, and outcome of congenital cystic adenomatoid malformation of lung (CCAM). Methods In this retrospective study, all 12 cases which were diagnosed with suspected prenatal CCAM over the period in the hospital were analyzed. Information on diagnosis time, types and progression of the lesions during pregnancy, the additional abnormalities, and the outcome of pregnancies were recorded. Results The positive rate of ultrasonic detection of CCAM was about 1.01‰ (1/11 124) before 28 gestation weeks. There were 1 case of type I (8%), 2 cases of type II (17%) and 9 cases of type III (75%). Nine pregnancies were terminated and 2 cases were confirmed by pathology. Three neonates were alive and without any symptom now. Conclusions Type III is the major type. Ultrasound examination during 20-28 weeks and following up, prenatal consultation, chromosome examination of fetus, delivery with a pediatrician standing by, and all suspected neonates being investigated are recommended.
基金Project supported by the National Natural Science Foundation of China(Grant No.10974105)the Double-Hundred Talent Plan,Shandong Province,China(Grant No.WST2018006)+1 种基金the Recruitment Program of High-end Foreign Experts,China(Grant Nos.GDW20163500110 and GDW20173500154)the Top-notch Innovative Talent Program of Qingdao City,China(Grant No.13-CX-8).One of the authors(Yi-Qian Wang)was sponsored by the Taishan Scholar Program of Shandong Province,China,the Qingdao International Center for Semiconductor Photoelectric Nanomaterials,China,and Shandong Provincial University Key Laboratory of Optoelectrical Material Physics and Devices,China.
文摘In this paper,we investigate the effects of lattice strain on the electrical and magnetotransport properties of La0.7Sr0.3MnO3(LSMO)films by changing film thickness and substrate.For electrical properties,a resistivity upturn emerges in LSMO films,i.e.,LSMO/STO and LSMO/LSAT with small lattice strain at a low temperature,which originates from the weak localization effect.Increasing film thickness weakens the weak localization effect,resulting in the disappearance of resistivity upturn.While in LSMO films with a large lattice strain(i.e.,LSMO/LAO),an unexpected semiconductor behavior is observed due to the linear defects.For magnetotransport properties,an anomalous in-plane magnetoresistance peak(pMR)occurs at low temperatures in LSMO films with small lattice strain,which is caused by two-dimensional electron gas(2DEG).Increasing film thickness suppresses the 2DEG,which weakens the pMR.Besides,it is found that the film orientation has no influence on the formation of 2DEG.While in LSMO/LAO films,the 2DEG cannot form due to the existence of linear defects.This work can provide an efficient way to regulate the film transport properties.
基金supported by the Shanghai Key Program of Clinical Science and Technology Innovation(17411950500,17411950501,18511105602)National Science Foundation of China(81741047,81971411)+2 种基金Shanghai Medical Center of Key Programs for Female Reproductive Diseases(2017ZZ01016)National Key Basic Research Plan of China(973 Plan)(2015CB943300)The Major Program of the National 13th Five-Year Plan of China(2016YFC1000400).
文摘Objective:Ultrasound determination of chorionicity is poor in early pregnancy in China.In an effort to increase the accuracy rate of prompt chorionicity determination,clinical training was provided to primary care physicians.This study assesses the effects of implementing clinical guidelines on chorionicity determination.Methods:A multi-centered cohort study was conducted between January 2014 and June 2017 in 12 hospitals without fetal medicine centers.In 2014,the obstetricians and ultrasound physicians were trained in clinical practice and ultrasound examination relating to chorionicity determination.Linear and binary regression analyses were conducted to identify the effects of introducing the new protocols,including the diagnosis rate of chorionicty and perinatal outcomes,taking the data from 2014 as a baseline.Pregnancy outcomes were additionally adjusted for maternal age.Results:During the period of this study,3,599 twin pregnancies from 12 centers were enrolled,and a total of 2,998 twin pregnancies were extracted.The rate of overall chorionicity determination,including antenatal and postpartum diagnosis,increased successively from 49.5% in 2014 to 93.5% in 2017(P<0.0001).The rate of ultrasonic chorionicity diagnosis before 14 weeks increased from 25.2% in 2014 to 65.0% in 2017(P<0.0001).These changes were associated with decreasing incidence of preterm birth,a lower risk of stillbirth,whether for one(P=0.0456 in 2016)or two fetuses(P=0.0470 in 2016;P=0.0042 in 2017)and a decreased rate of admission to neonatal intensive care unit(43.0% in 2014,37.4% in 2017;P=0.0032).Conclusions:The implementation of a clinical practice guideline improved both overall and early chorionicity determinations.Regular training workshops of antenatal care are recommended to further promote capability in clinical diagnosis and treatment.
基金This study was supported by the National Key R and D Program of China(2016YFC1000403)the National Nature Science Foundation of China(81601311 and 81300491).
文摘Objective::The role of Vitamin D-binding protein(DBP)in preeclampsia(PE)pathogenesis is unknown.In this study,we compared the expression of DBP in the placentas of PE patients with the placentas of normotensive pregnant women with placenta previa controls,and aimed to explore the effect of DBP on endothelial cells(ECs)and the underlying mechanism.Methods::DBP expression in placental tissues collected from PE patients and controls was evaluated by immunohistochemistry.The downregulation and upregulation of DBP expression in HTR-8/SVneo cells were examined using DBP-targeting small interfering RNA(siRNA)and DBP-expression vector,respectively.The conditioned media of these DBP-overexpressing and DBP-siRNA HTR-8/SVneo cells were collected and added to human umbilical vein EC(HUVEC)cultures.Angiogenic effects on HUVECs were assessed by tube formation assays,and the proliferation and migration of HUVECs were examined using the Real-Time Cell Analyzer.The expression of vascular endothelial growth factor(VEGF)and VEGF receptor(VEGFR)-2,as well as the phosphorylation of different residues of VEGFR-2 in HUVECs,were determined by western blotting.Results::DBP expression was significantly increased in the placental tissues collected from PE patients.The conditioned medium of DBP-overexpressing HTR-8/SVneo cells potently inhibited tube formation by HUVECs,in addition to their proliferation and migration.Furthermore,treatment of HUVECs with the conditioned medium of DBP-overexpressing HTR-8/SVneo cells decreased the phosphorylation of VEGFR-2 at tyrosine 996,whereas the treatment of these cells with the conditioned medium of DBP-siRNA HTR-8/SVneo cells increased the phosphorylation of VEGFR-2 at tyrosine 951,996,and 1,175.Conclusions::The expression of DBP is increased in the placentas of PE patients.DBP plays potential roles in endothelial dysfunction,which contributes to PE development,by inhibiting tyrosine phosphorylation of VEGFR-2 in ECs.
基金National Natural Sciences Foundation of China(81971408,81801469,81801468,and 81971411)National Key R&D Program of China(2016YFC1000403)2020"Diligence·Excellence"Clinical Innovative Team Project"Study on the comprehensive management of preeclampsia and its pathogenesis"conducted by Obstetrics and Gynecology Hospital of Fudan University(2021fckbc06)
文摘Objective:Long non-coding RNAs(lncRNAs)are implicated in multiple pathophysiological processes in placenta-related disorders;however,their expression and function in late-onset pre-eclampsia(LOPE)remain unclear.This study aimed to investigate the expression of lncRNAs in LOPE,construct a competing endogenous RNA(ceRNA)network,and identify the pathways associated with LOPE pathogenesis.Methods:We performed lncRNA and mRNAs microarray profiling to identify the differential expression profiles of lncRNAs and mRNAs in LOPE compared to those in normal pregnancy.Quantitative reverse transcription polymerase chain reaction(qRT-PCR)was performed to validate differentially expressed genes.Subsequently,we generated an interaction network between lncRNAs,(micro-RNAs)miRNAs,and mRNAs based on the Pearson’s correlation coefficient between lncRNAs and mRNAs.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed to understand the functional significance of differentially expressed lncRNAs(DElncRNAs)in LOPE.Results:We identified 29 DElncRNAs(25 upregulated and four downregulated)and 212 differentially expressed mRNAs(DEmRNAs;203 upregulated and nine downregulated)in LOPE placentas.Within them,six lncRNAs and four mRNAs were verified by qRT-PCR.GO and KEGG analyses revealed the potential pathways affected by these mRNAs,such as positive regulation of leukocyte chemotaxis,chemokine signaling pathway,and response to hypoxia.Finally,we constructed a ceRNA network including three DElncRNAs and 124 DEmRNAs,whose competing interactions may be mediated by 17 miRNAs.Two DElncRNAs,ENST00000515376 and ENST00000520544,were found to be hub genes,as they interacted with most miRNAs and mRNAs.ENST00000515376 is most likely related to the metabolic process of arachidonic acid,whereas ENST00000520544 is more likely related to the coagulation system,such as the regulation of blood coagulation and platelet degranulation.Conclusion:Differential expression profile of lncRNAs and the lncRNA-miRNA-mRNA network in LOPE provide potential therapeutic targets for this disease.
基金This work was supported by grants from the Shanghai Key Program of Clinical Science and Technology Innovation(No.17411950500 ,No.18511105602)Shanghai Medical Center of Key Programs for Female Reproductive Diseases(No.2017ZZ01016).
文摘Background:China’s two-child policy has led to a trend of aging in pregnancy which was associated with adverse outcomes.This study aimed to identify the clinically cutoff maternal age for adverse obstetric outcomes in China.Methods:This secondary analysis of a multicenter retrospective cohort study included data of childbearing women from 39 hospitals collected in urban China during 2011 to 2012.Logistic regression was used to assess the adjusted odds ratios(aOR)of adverse outcomes in different age groups in comparison to women aged 20 to 24 years.The adjustments included the location of the hospital,educational level,and residence status.Clinically cutoff age was defined as the age above which the aOR continuously become both statistically(P<0.05)and clinically(aOR>2)significant.Results:Overall,108,059 women were recruited.In primiparae,clinically cutoff maternal ages for gestational diabetes(aOR:2.136,95%confidence interval[CI]:1.856-2.458,P<0.001),placenta previa(aOR:2.400,95%CI:1.863-3.090,P<0.001),cesarean section(aOR:2.511,95%CI:2.341-2.694,P<0.001),hypertensive disorder(aOR:2.122,95%CI:1.753-2.569,P<0.001),post-partum hemorrhage(aOR:2.129,95%CI:1.334-3.397,P<0.001),and low birth weight(aOR:2.174,95%CI:1.615-2.927,P<0.001)were 27,31,33,37,41,and 41 years,respectively.In multiparae,clinically cutoff ages for gestational diabetes(aOR:2.977,95%CI:1.808-4.904,P<0.001),hypertensive disorder(aOR:2.555,95%CI:1.836-3.554,P<0.001),cesarean section(aOR:2.224,95%CI:1.952-2.534,P<0.001),post-partum hemorrhage(aOR:2.140,95%CI:1.472-3.110,P<0.001),placenta previa(aOR:2.272,95%CI:1.375-3.756,P<0.001),macrosomia(aOR:2.215,95%CI:1.552-3.161,P<0.001),and neonatal asphyxia(aOR:2.132,95%CI:1.461-3.110,P<0.001)were 29,31,33,35,35,41,and 41 years,respectively.Conclusions:Early cutoff ages for gestational diabetes and cesarean section highlight a reasonable childbearing age in urban China.The various optimized cutoff ages for different adverse pregnancy outcomes should be carefully considered in childbearing women.
文摘Objective:The aim of the study is to investigate the relationship between antenatal depression and adverse perinatal outcomes.Methods:This prospective cohort study enrolled pregnant women between gestational ages of 12-20 weeks to complete the Chinese version of the Zung Self-Rating Depression Scale(SDS)and followed them for delivery from September 2015 to September 2016.Participants were classified into mild,moderate,and severe depression groups according to the SDS scores.Logistic regression was performed to assess the association between antenatal depression and perinatal outcomes including preterm birth(PTB),cesarean section use,hypertension disorders,gestational diabetes,and thyroid diseases during pregnancy.An age-stratified analysis was performed.Results:A total of 4,663 pregnant women were analyzed.As a result,13.8%,1.7%,and 0.2%of women were classified as mild,moderate,and severe depression,respectively.Severely depressed mothers were at higher risk for PTB(adjusted odds ratio[OR]=11.31,95%confidence interval[CI]2.13-60.03),especially spontaneous PTB.Moderate-depressed women were at higher risk for hyperthyroidism during pregnancy(adjusted OR=3.67,95%CI 1.10-12.27),while women with mild depression tended to choose cesarean sections(OR=1.24,95%CI=1.04-1.49).Age-stratified analysis indicated an elevated risk of adverse outcomes associated with depression in women aged<25 years,but the association was not significant.Conclusions:Antenatal depression was associated with PTB,hyperthyroidism,and cesarean use.Studies with large sample sizes should verify the relationship between PTB and antenatal depression to avoid casual events.
基金This study was supported by the Program of Shanghai Leading Talent(2012),Shanghai Key Program of Clinical Science and Technology Innovation(17411950500,17411950501,18511105602)National Science Foundation of China(81741047,81971411,81571460)+3 种基金Shanghai Medical Center of Key Programs for Female Reproductive Diseases(2017ZZ01016)National Key Basic Research Plan of China(973 Plan)(2015CB943300)National Key R&D Program of China(2016YFC1000403)The Major Program of the National 13th Five-Year Plan of China(2016YFC1000400).
文摘Objective: To characterize and compare the microbiome signature in the maternal, intrauterine, and fetal environments and the associated bacterial species in women who experienced preterm birth and term birth.Methods: A total of 140 women with singleton pregnancies were enrolled in this study. Among them, 31 experienced spontaneous preterm delivery (gestational age < 37 weeks), and 28 of them experienced vaginal delivery at term. Maternal peripheral blood, saliva, and vaginal discharge samples and fetal membrane, amniotic fluid, and cord blood samples were collected immediately after delivery under sterile conditions. DNA was isolated from the fetal membrane and umbilical cord blood samples, and the V3-V4 region of the bacterial 16S rRNA gene was sequenced. The sequence data were quality-filtered, chimera-checked, and organized into operational taxonomic units (OTUs) based on phylogeny. Principal coordinate analysis of beta diversity measures was used for visualization. The linear discriminant analysis effect size (LEfSe) algorithm and Wilcoxon test were used to differentiate the microbiomes found in the fetal membranes and cord blood in the cases of preterm birth.Results: OTU analysis based on the 16S rRNA gene showed similar microbiomes in the maternal peripheral blood, amniotic fluid, fetal membranes, and cord blood. However, the LEfSe algorithm revealed significantly different bacterial compositions in the fetal environment between the preterm and term groups, with some of the bacterial species originating from the maternal peripheral blood or saliva.Conclusions: The bacteria in the intrauterine and fetal environments may originate from other body sites through hematogenous transmission, and may cause the occurrence of preterm birth.
