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Objective @#To investigate the role of lncSIL in transforming growth factor-β1(TGF-β1)-induced alveo- lar epithelial interstitial transformation (EMT) and its related signaling pathways .@*Methods @#Western blot was used to detect the effect of lncSIL silencing on the expression of E-cadherin ( E-cad) , alpha-smooth muscle actin ( α- SMA) and Collagen I (Col I) in the process of EMT induced by TGF-β1 . LncSIL interacting proteins were ana- lyzed by RNA pulldown . Western blot was used to detect the effect of overexpression or silencing of lncSIL on the expression of its target gene enhancer of zeste homolog 2 (EZH2) and its downstream factors P21 and cyclin-de- pendent kinase 6 (CDK6) . Flow cytometry was used to analyze the effect of lncSIL on cell cycle progression .@*Results@#After lncSIL silencing , the expression of α-SMA and Col I increased , the expression of E-cad decreased . RNA pulldown assay showed that EZH2 was the target protein that interacted with lncSIL , and the expression of EZH2 increased after silencing lncSIL , the expression of EZH2 downstream gene P21 decreased , CDK6 increased . Flow cytometry showed that the number of cells in S phase significantly increased . When lncSIL was overexpressed , the expression of EZH2 and CDK6 was down-regulated , the expression of P21 was up-regulated , and the number of S phase cells significantly decreased .@*Conclusion @#LncSIL inhibits TGF-β1-induced alveolar epithelial cell mesen- chymal transition by negatively regulating EZH2/P21 /CDK6 signaling pathway to inhibit cell cycle progression .
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Objective To establish a risk prediction model,and to observe its value for predicting retained cesarean scar pregnancy(CSP)after ultrasound-guided curettage.Methods Data of 401 CSP patients who received ultrasound-guided curettage were retrospectively analyzed.The patients were randomly divided into training set(n=264)or validation set(n=137)at a ratio of 7:3.According to whether there was retained CSP at the lower segmental scar of uterine after ultrasound-guided curettage,the patients were divided into retained group or non-retained group.The variables with the biggest predictive value for retained CSP after ultrasound-guided curettage were selected with LASSO regression,and the independent risk factors were screened using multivariate logistic regression,and then a nomogram model was established.Results The results of LASSO regression and multivariate logistic regression indicated that embedded depth of gestational sac in cesarean scar more than 1.13 cm,convexity of gestational sac,rich blood supply(Adler degree Ⅱ-Ⅲ),and pre-curettage serum β-human chorionic gonadotropin(HCG)more than 33 063.50 U/L were all independent risk factors for retained CSP after curettage(all P＜0.05).The calibration curve of nomogram predictive model established based on the above indexes was basically consistent with the ideal curve,and the model had good clinical benefits.Conclusion The established nomogram predictive model had good predictive ability for retained CSP after curettage.
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Objective:To investigate the value of ultrasonography in diagnosis of transposition of great arteries of the fetus at 11-13 + 6 weeks gestation. Methods:A prospective study was conducted on fetuses screened by ultrasound in the first trimester in Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region between January 2015 and March 2022. Fetal heart structure was screened by three-section screening method. Fetuses with suspected transposition of the great arteries at 11-13 + 6 weeks gestation underwent followed-up ultrasound examination, chromosome and gene test results. The ultrasound characteristics and prognosis pregnancy outcomes were summarized. Results:Twenty-one cases of transposition of the great arteries were detected by ultrasonography, including complete transposition of great arteries (20 cases) and congenitaly corrected transposition of the great arteries (1 case). Two cases were miss diagnosed. Twenty-one cases showed parallel signs of two major arteries on grayscale outflow section at 11-13 + 6 weeks gestation. There were 6 cases with aneuploid ultrasonographic soft markers abnormality, 2 cases with extracardiac malformation. Chromosome and microarray analysis were performed in 13 cases. 4 cases with chromosomal abnormality. Four cases of chromosomal abnormalities were associated with ultrasonographic soft markers abnormality, and 1 case with extracardiac malformation.In the 23 cases, 20 cases were induced, 1 miscarried, and 2 delivered to term. Among the fetuses delivered at term, 1 case died before neonatal operation and 1 case survived. Conclusions:Standardized ultrasound scan at 11-13 + 6 weeks has high accuracy in diagnosis of transposition of the great arteries. And the incidence of chromosomal abnormality is high with ultrasonographic soft markers abnormality or extracardiac malformation.
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Objective:To establish the normal reference range of the ratio of fetal umbilical venous flow rate to umbilical artery pulsatility index (VAI).Methods:A total of 816 normal fetuses underwent prenatal examination and delivery were randomly selected from October 2018 to December 2020 in Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region. Fetal weight was obtained by measuring fetal biparietal diameter, head circumference, abdominal circumference, and femoral length.Umbilical venous flow (Quv) was measured. Umbilical artery pulsatility index (UA-PI) was obtained in the free segment of amniotic fluid. Quv was standardized according to fetal size to calculate the umbilical venous flow rate (nQuv) and VAI. The association between Quv, nQuv, UA-PI, VAI and the fetal gestational week were analyzed using correlation analysis. VAI was presented as ± s, the upper limit of 95% reference value and the lower limit of 5% reference value were taken as the standards of VAI increase and decrease, respectively. Twenty-six fetuses whose VAI were lower than limit of 5% and 20 fetuse whose VAI were than limit of 95% were chosed as the case group. Results:①Fetal Quv was positively correlated with gestational week ( r=0.893, P<0.001), nQuv and UA-PI were negatively correlated with gestational week ( r=-0.552, -0.827; all P<0.001), and VAI had no significant correlation with gestational week ( r=0.000, P=0.758); ②The mean, standard deviation, lower 5% reference value, and upper 95% reference value of VAI were 195.81, 55.61, 105.95, and 293.33, respectively; ③In the cases with abnormal VAI, 26 fetuses with reduced VAI, of whom there were 16 cases of maternal hypertension, and 13 cases complicated by severe preeclampsia; 1 case with 40 turns of umbilical cord torsion, 3 cases of stillbirth, 16 cases of preterm delivery, 19 cases of low neonatal birth body weight, 4 cases of 1-min Apgar score ≤7, 6 cases of umbilical artery blood pH<7.2, and 1 case without abnormalities in fetus during pregnancy and follow-up newborn. Among the 20 fetuses with increased VAI, there were 10 cases of fetal severe thalassemia, 2 cases of thalassemia, 1 case of sacrococcygeal teratoma, 1 case of portal venous shunt, 3 cases of placental chorioangioma, and 3 cases without abnormalities in fetus during pregnancy and follow-up newborn. Conclusions:The measurement and calculation of fetal VAI is simple and easy to perform. As a comprehensive index, fetal VAI remains constant in mid and late pregnancy, facilitates the follow-up of abnormal fetuses, and has potential clinical application.
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Objective:To investigate the value of atrioventricular valve regurgitation in predicting atrioventricular septal defect (AVSD) in the first trimester.Methods:Fetuses were examined prospectively by ultrasound at 11-13 + 6 weeks in Maternity & Child Healthcare Hospital of Guangxi Zhuang Autonomous Region between February 2016 and February 2021. Congenital heart disease was screened and atrioventricular valve regurgitation was observed in fetuses of gestational age 11 to 13 + 6 weeks using color Doppler in four-chamber view and three vessels and trachea view. Results:Totally 43 549 fetuses of gestational age 11 to 13 + 6 weeks were screened by echocardiography, of whom 37 cases were screened out with AVSD, including complete atrioventricular septal defect (31 cases), partial atrioventricular septal defect(3 cases) and intermediate atrioventricular septal defect(1 cases), 2 cases were misdiagnosed, and ultrasonic scanning in the second trimester found 2 missed cases of intermediate atrioventricular septal defect. Atrioventricular valve regurgitation was observed in 91.89% of atrioventricular septal defects (34/37) in the first trimester, 59.46% (22/37) nuchal translucency greater than 95th percentile, 29.73% (11/37) absence of nasal bone, 32.43% (12/37) ductus venosus A wave inversion, and 40.54% (15/37) had tricuspid regurgitation. The sensitivity of common atrioventricular valve regurgitation in predicting atrioventricular septal defect is better than other ultrasonic indexes. Conclusions:Atrioventricular regurgitation can be used as a clue to predict atrioventricular septal defect in the first trimester, which is beneficial to detect atrioventricular septal defect in the first trimester.
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Objective:To assess the value of ultrasonography in the diagnosis of fetal isomerism syndrome in the first trimester.Methods:Sonographic features of 15 fetuses with isomerism syndrome diagnosed in the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region from January 2015 to March 2020 were reviewed. Ultrasonic characteristics in the first trimester were analyzed, and the ultrasonic characteristics of early mid-trimester and pathological anatomical results were combined for comparison.Results:There were 6 cases of left isomerism syndrome (LIS) and 9 cases of right isomerism syndrome (RIS) in the 15 fetues.Increased nuchal translucency(NT) (≥3.0 mm, 6 cases), reversed A wave in ductus venosus (10 cases), and atrio-ventricular valve regurgitation (14 cases) were found during the first trimester. There were 14 cases with abnormal visceral laterality. Of the 15 fetues, 14 cases with cardiac malformations, including 6 cases of functional single ventricle, 8 cases of complete atrioventricular septal defect (CAVSD), and 12 cases with great artery abnormalities. All of the 6 LIS cases had bradycardia, 3 cases had interruption of inferior vena cava (IVC). Six cases of RIS had juxtaposition of descending aorta and IVC, and 1 case of RIS had total anomalous pulmonary vein drainage. The major structural malformations were consistent with the early mid-trimester ultrasound examination or autopsy. Karyotype and chromosomal microarray were available in 12 cases and all were normal.Conclusions:Isomerism syndrome has high positive rate of fetal aneuploidies ultrasonographic marker, especially with the atrio-ventricular valve regurgitation, but the risk of chromosome abnormality is low. Ultrasound screening for fetal cardiac structural abnormalities is beneficial to the early diagnosis of isomerism syndrom in the first trimester.
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Objective:To explore the feasibility and prognosis of prenatal ultrasonic diagnosis of fetal isolated vascular ring at 11-13 + 6 weeks. Methods:A total of 36 996 fetuses were selected to compare the results of ultrasound screening at 11-13 + 6 weeks and 20-24 weeks of pregnancy in Guangxi Maternity & Child Healthcare Hospital from January 2016 to January 2020, the reasons for missed diagnosis and misdiagnosis of fetal isolated vascular ring by ultrasonography in the first trimester were summarized. Results:Thirty-five cases were diagnosed as isolated vascular ring in the first trimester, including 19 cases right aortic arch combined with aberrant left subclavian artery with "U-shaped" vascular ring, 7 cases double aortic arch with "O-shaped" vascular ring, and 9 cases aberrant right subclavian artery with "C-shaped" vascular ring. While 155 cases were diagnosed as isolated vascular ring at 20-24 weeks of pregnancy, consisting of 18 cases of combined with aberrant left subclavian artery, 9 cases of double aortic arch, 126 cases of aberrant right subclavian artery and 2 cases of pulmonary artery sling, the diagnosis coincidence rates were 94.74%, 77.78%, 7.14%, 0(Kappa value were 0.97, 0.88, 0.13, 0). For the diagnosis of right aortic arch combined with aberrant left subclavian artery, double aortic arch and aberrant right subclavian artery in the first trimester, the specificities were 99.99%, 100%, 100%, the sensitivities were 100%, 77.78%, 7.14%, the false-positive rates were 0.01%, 0, 0, the false-negative rates were 0, 22.22%, 92.86%, and the Youden′s indices were 0.99, 0.78, 0.07.Conclusions:Right aortic arch combined with aberrant left subclavian artery and double aortic arch have high coincidence rate by ultrasonography in the first trimester, while the diagnostic coincidence rate of isolated aberrant right subclavian artery was low. Ultrasound screening for isolated vascular ring in the first trimester still needs ultrasound examination in the second trimester to exclude the minor cardiac malformations that are difficult to diagnose in the first trimester.
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miRNAs are important regulators of plant gene expression. There are few studies on the regulation of miRNAs in Lonicera edulis. We used high-throughput sequencing technology to analyse miRNAs in L. edulis, aiming to identify miRNAs and elucidate their function in L. edulis. In the present study, we employed the high-throughput sequencing technology to profile miRNAs in L. edulis. A total of 51,819,072 small RNA tags with sizes ranging from 18 to 30 nt were obtained, indicating that L. edulis have a large and diverse small RNA population. Bioinformatic analysis identified 507 mature miRNAs, and 16 predicted novel miRNAs that are likely to be unique to L. edulis. Three miRNAs related to anthocyanin biosynthesis were locked by gene ontology (GO) analysis and target gene analysis. The selected three miRNAs are relatively high in the expression of L. edulis. Some of the previous studies have studied these types of miRNAs involved in the anthocyanin metabolism pathway in fruits. Among them, expression profiles of three conserved miRNAs were validated by stem loop qRT-PCR. Further, the potential target genes of conserved and novel miRNAs were predicted and subjected to GO annotation. Enrichment analysis of the GO-represented biological processes and molecular functions revealed that these target genes were potentially involved in a wide range of metabolic pathways and developmental processes. In particular, different families of miRNAs can directly or indirectly regulate anthocyanin biosynthesis. In recent years, the research on miRNAs has become more and more clear, but the research on miRNAs involved in the regulation of anthocyanin synthesis of L. edulis is still lagging. This study provides a useful resource for further elucidation of the functional roles of miRNAs during fruit development and ripening
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Purpose@#Combining targeted agents with adjuvant chemotherapy prolongs survival in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients, but also increases the risk of adverse effects. The updated results of 3 randomized controlled trials (RCTs) were reported in 2019. Given the lack of adequate head-to-head pairwise assessment for anti-HER2 agents, network meta-analysis facilitates obtaining more precise inference for evidence-based therapy. @*Methods@#RCTs comparing at least 2 anti-HER2 regimens in an adjuvant setting for HER2-positive early-stage breast cancer (EBC) were included. Hazard ratios for overall survival (OS) and disease free survival (DFS), with respective 95% confidence intervals were pooled for assessment of efficacy. A Bayesian statistical model was used, and odds ratios (ORs) for adverse events (AEs) were used to pool effect sizes. @*Results@#We demonstrated that 1-year trastuzumab plus chemotherapy had increased efficacy compared to shorter or longer treatment duration. The OR of cardiac events gradually increased from 6 months to 1 and 2-year trastuzumab arms, relative to chemotherapy only.Compared to trastuzumab plus chemotherapy, dual HER2-targeting therapies increased DFS, especially for hormone receptor negative patients. Dual anti-HER2 blockade regimens revealed an increased probability of gastrointestinal reactions. As a second agent, pertuzumab showed significantly higher DFS and OS. @*Conclusion@#We conclude that 1-year adjuvant trastuzumab should remain as the standard treatment for HER2-positive EBC patients, as it has greater efficacy and a manageable proportion of AEs. Clinical efficacy can be increased for hormone receptor-negative tumors by including a second HER2-targeted agent to the treatment regimen. For hormone receptorpositive cases with basal disease, it is acceptable to reduce the risk of cardiotoxicity by shortening the duration of trastuzumab.
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Objective:To investigate the echocardiographic characteristics, pathological anatomy and genetic abnormality of congenital absent semilunar valves in first trimester.Methods:Eleven cases of congenital absent semilunar valve fetus diagnosed at 11-13 + 6 weeks of gestation in Guangxi Magernity & Child Healthcare Hospital from December 2014 to December 2018 were analyzed. The characteristics of echocardiography and the abnormal microanatomy of cardiac tissue after labor induction was compared. Results:The crown-lump length of the 11 fetus was 46-74(62.0±9.2)mm, and nuchal translucency thickness(NT) was 2.4-10.4 (6.4±2.6)mm. The NT of 10 cases were greater than 3.0 mm. Color Doppler flow imaging revealed that biphasic bidirectional flow in the aortic arch and/or pulmonary artery at the 3VT view( "to-and-fro" ) in those 11 cases, and pansystolic turbulence and pandiastolic reflux spectrum were showed on spectral Doppler. Among them, there were 10 cases of " stealing type" , including 2 cases of isolate absent aortic valves, 3 cases of absent pulmonary valves and 5 cases of absent both aortic and pulmonary valves; and all the 10 cases had secondary ultrasonic manifestations of fetal heart failure. Chromosome analysis and detection of genes showed that 4 cases with Trisomy 13 syndrome, 3 cases with Trisomy 18 syndrome, 1 case with 22q11.2 deletion, 1 case with 12q24.32q24.33 deletion and 1 case was normal. Pathological anatomy revealed enlarged heart in 8 cases, isolate absent aortic valves in 2 cases (1 case complicated with pulmonary atresia, absence of ductus arteriosus and thymus), absent pulmonary valves in 3 cases, absent both aortic and pulmonary valves in 3 cases, relics of semilunar valves in 3 cases. And 2 cases of absent pulmonary valves and 3 cases of absent both aortic and pulmonary valves with short and thick ductus arteriosus. Only 1 case was congenital absent semilunar valve in " non-stealing type" without secondary ultrasonic manifestations of fetal heart failure. Chromosome analysis and detection of genes showed 22q11.2 deletion, and there were relics of semilunar valves in the pathological anatomy. It also combined with tetralogy of Fallot and absence of ductus arteriosus.Conclusions:In first trimester, congenital absent semilunar valves are more common as " stealing type" . The echocardiographic features of congenital absent semilunar valves are the " in-out sign" of aorta arch and/or pulmonary artery and biphasic spectrum in spectral Doppler. Trisomy 13 syndrome and trisomy 18 syndrome significantly increased the risk of congenital absent semilunar valves in " stealing type" in first trimester.
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Objective:To explore the values of Z-scores of fetal heart circumference (HC) and heart area (HA) in prediction of homozygous α-thalassemia.Methods:From February 2014 to March 2019, 233 fetuses of 15 to 23 gestation weeks with risk of homozygous α-thalassemia were examined by prenatal ultrasound in the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region. HC, HA and cardiothoracic ratio (CTR) were measured. HC and HA were converted into Z-scores, respectively. The ROC curves were established and analyzed based on HC Z-score, HA Z-score or CTR respectively to compare their predicting efficacies for fetal homozygous α-thalassemia. Finally, the sensitivity, specificity, positive predictive value and negative predictive value were obtained by the best cutoff values.Results:①Sixty-five fetuses were diagnosed as homozygous α-thalassemia and classified as α-thalassemia group. One hundred and sixty-eight fetuses were mild and normal and were classified as control group. ②HC Z-score, HA Z-score and CTR in the α-thalassemia group were significantly higher than those in the control group, and the differences between the two groups were statistically significant ( P<0.001). ③The area under ROC curve of HA Z-score was the largest compared with HC Z-score and CTR, and the prediction efficacy was the highest ( Z test=2.144 and 2.517 respectively, P<0.05). ④The best cutoff values were HC Z-score>1.67, HA Z-score>2.06 and CTR>0.53. Sensitivities of predicting homozygous α-thalassemia in 15 to 23 gestation weeks were 92.31%, 100% and 89.23%, respectively. Specificities were 94.05%, 95.83% and 93.45%, respectively. Positive predictive values were 84.43%, 89.00% and 84.05%, respectively. Negative predictive values were 96.91%, 100% and 95.57%, respectively. Conclusions:Fetal heart HC Z-score and HA Z-score are safe and effective novel ultrasonic indexes for predicting homozygous α-thalassemia. Especially compared with traditional CTR, HA Z-score has a significantly higher predicting efficacy, which can improve the detection rate of homozygous α-thalassemia and reduce the need for invasive examination.
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Objective:To construct Z-score ranges for normal fetal middle cerebral artery peak systolic velocity(MCA-PSV).Methods:From May 2017 to October 2019, 865 normal singleton fetuses of 10th to 40th gestational weeks underwent prenatal ultrasound in the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region. Using fetal biometric parameters as independent variables, and measurement of MCA-PSV on standard section as dependent variables, the regression analyses of the mean(M) and the standard deviation(SD) for each parameter were calculated separately and then the best fitting equation was selected. A group of diseases which might cause the abnormal MCA-PSV were assessed using these standards.Results:①Strong correlations were found between MCA-PSV and fetal biometric parameters ( r=0.935-0.939, P<0.001). ②Quadratic or cubic regression equations were fitted to the models of the means of the MCA-PSV, whereas linear equations were fitted to the SDs. ③In these case groups, intrauterine growth restriction, severe preeclampsia, intrauterine infection and homozygous α-thalassemia-1 demonstrated Z-score>2 reflective of increased MCA-PSV with varying degrees, especially with the homozygous α-thalassemia-1 fetus being the most significant (17/20, 85%). Conclusions:The calculation of Z-score for MCA-PSV as a function of fetal biometric parameters is intuitive and simple, it can be used as an important indicator especially for homozygous α-thalassemia-1.
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Objective@#To investigate the echocardiographic characteristics, pathological anatomy and genetic abnormality of congenital absent semilunar valves in first trimester.@*Methods@#Eleven cases of congenital absent semilunar valve fetus diagnosed at 11-13+ 6 weeks of gestation in Guangxi Magernity & Child Healthcare Hospital from December 2014 to December 2018 were analyzed. The characteristics of echocardiography and the abnormal microanatomy of cardiac tissue after labor induction was compared.@*Results@#The crown-lump length of the 11 fetus was 46-74(62.0±9.2)mm, and nuchal translucency thickness(NT) was 2.4-10.4 (6.4±2.6)mm. The NT of 10 cases were greater than 3.0 mm. Color Doppler flow imaging revealed that biphasic bidirectional flow in the aortic arch and/or pulmonary artery at the 3VT view( "to-and-fro" ) in those 11 cases, and pansystolic turbulence and pandiastolic reflux spectrum were showed on spectral Doppler. Among them, there were 10 cases of " stealing type" , including 2 cases of isolate absent aortic valves, 3 cases of absent pulmonary valves and 5 cases of absent both aortic and pulmonary valves; and all the 10 cases had secondary ultrasonic manifestations of fetal heart failure. Chromosome analysis and detection of genes showed that 4 cases with Trisomy 13 syndrome, 3 cases with Trisomy 18 syndrome, 1 case with 22q11.2 deletion, 1 case with 12q24.32q24.33 deletion and 1 case was normal. Pathological anatomy revealed enlarged heart in 8 cases, isolate absent aortic valves in 2 cases (1 case complicated with pulmonary atresia, absence of ductus arteriosus and thymus), absent pulmonary valves in 3 cases, absent both aortic and pulmonary valves in 3 cases, relics of semilunar valves in 3 cases. And 2 cases of absent pulmonary valves and 3 cases of absent both aortic and pulmonary valves with short and thick ductus arteriosus. Only 1 case was congenital absent semilunar valve in " non-stealing type" without secondary ultrasonic manifestations of fetal heart failure. Chromosome analysis and detection of genes showed 22q11.2 deletion, and there were relics of semilunar valves in the pathological anatomy. It also combined with tetralogy of Fallot and absence of ductus arteriosus.@*Conclusions@#In first trimester, congenital absent semilunar valves are more common as " stealing type" . The echocardiographic features of congenital absent semilunar valves are the " in-out sign" of aorta arch and/or pulmonary artery and biphasic spectrum in spectral Doppler. Trisomy 13 syndrome and trisomy 18 syndrome significantly increased the risk of congenital absent semilunar valves in " stealing type" in first trimester.
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Purpose@#Combining targeted agents with adjuvant chemotherapy prolongs survival in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients, but also increases the risk of adverse effects. The updated results of 3 randomized controlled trials (RCTs) were reported in 2019. Given the lack of adequate head-to-head pairwise assessment for anti-HER2 agents, network meta-analysis facilitates obtaining more precise inference for evidence-based therapy. @*Methods@#RCTs comparing at least 2 anti-HER2 regimens in an adjuvant setting for HER2-positive early-stage breast cancer (EBC) were included. Hazard ratios for overall survival (OS) and disease free survival (DFS), with respective 95% confidence intervals were pooled for assessment of efficacy. A Bayesian statistical model was used, and odds ratios (ORs) for adverse events (AEs) were used to pool effect sizes. @*Results@#We demonstrated that 1-year trastuzumab plus chemotherapy had increased efficacy compared to shorter or longer treatment duration. The OR of cardiac events gradually increased from 6 months to 1 and 2-year trastuzumab arms, relative to chemotherapy only.Compared to trastuzumab plus chemotherapy, dual HER2-targeting therapies increased DFS, especially for hormone receptor negative patients. Dual anti-HER2 blockade regimens revealed an increased probability of gastrointestinal reactions. As a second agent, pertuzumab showed significantly higher DFS and OS. @*Conclusion@#We conclude that 1-year adjuvant trastuzumab should remain as the standard treatment for HER2-positive EBC patients, as it has greater efficacy and a manageable proportion of AEs. Clinical efficacy can be increased for hormone receptor-negative tumors by including a second HER2-targeted agent to the treatment regimen. For hormone receptorpositive cases with basal disease, it is acceptable to reduce the risk of cardiotoxicity by shortening the duration of trastuzumab.
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PURPOSE@#C-terminal binding protein 1 (CtBP1) is a transcriptional co-repressor that is overexpressed in many cancers. CtBP1 transcriptionally represses a broad array of tumor suppressors, which promotes cancer cell proliferation, migration, invasion, and resistance to apoptosis. Recent studies have demonstrated that CtBP1 is a potential target for cancer therapy. This study was designed to screen for compounds that potentially target CtBP1.@*METHODS@#Using a structure-based virtual screening for CtBP1 inhibitors, we found protocatechuic aldehyde (PA), a natural compound found in the root of a traditional Chinese herb, Salvia miltiorrhiza, that directly binds to CtBP1. Microscale thermophoresis assay was performed to determine whether PA and CtBP1 directly bind to each other. Further, clustered regularly interspaced short palindromic repeats associated Cas9 nuclease-mediated CtBP1 knockout in breast cancer cells was used to validate the CtBP1 targeting specificity of PA.@*RESULTS@#Functional studies showed that PA repressed the proliferation and migration of breast cancer cells. Furthermore, PA elevated the expression of the downstream targets of CtBP1, p21 and E-cadherin, and decreased CtBP1 binding affinity for the promoter regions of p21 and E-cadherin in breast cancer cells. However, PA did not affect the expression of p21 and E-cadherin in the CtBP1 knockout breast cancer cells. In addition, the CtBP1 knockout breast cancer cells showed resistance to PA-induced repression of proliferation and migration.@*CONCLUSION@#Our findings demonstrated that PA directly bound to CtBP1 and inhibited the growth and migration of breast cancer cells through CtBP1 inhibition. Structural modifications of PA are further required to enhance its binding affinity and selectivity for CtBP1.
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Asunto(s)
Humanos , Biomarcadores , Neoplasias de la Mama , Mama , Quimioterapia , Terapia Neoadyuvante , Neoplasia Residual , Patología , Pronóstico , United States Food and Drug AdministrationRESUMEN
Objective@#To investigate the efficacy of periprocedural use of bivalirudin for patients with chronic total occlusion(CTO) lesion undergoing percutaneous coronary intervention(PCI) therapy. @*Methods@#In this randomized controlled study, 74 patients with CTO lesions confirmed by coronary angiography or CT angiography, hospitalized in the general hospital of Shenyang military region from September 2015 to December 2016, were randomly divided into unfractionated heparin(UFH) group (n=38) and bivalirudin group (n=36) by the random number table.Patients in the UFH group were treated with injection of UFH 5 000 U through the artery sheath catheter before coronary angiography,and the UFH was intravenously administered at 100 U/kg before PCI. Patients in the bivalirudin group received intravenous injection of bivalirudin (0.75 mg/kg) before coronary angiography, followed by intravenous infusion of 1.75 mg·kg-1·h-1 until at least 2 hours after the PCI. The values of the activated coagulation time (ACT) were measured,and the value was remained at 250 to 350 seconds during the PCI. The incidence rate of adverse events including hemorrhage events, no-reflow/slow flow, and contact thrombus in perioperative period were observed in all patients. In addition, the incidence rate of the major adverse cardiovascular events (MACE) including recurrent angina, heart failure, target vessel revascularization, cardiac death, non-fatal myocardial infarction,and stroke within 1 year follow-up period were also observed in the 2 groups. @*Results@#Baseline clinical and PCI data were similar between the 2 groups (all P>0.05). During the perioperative period, the incidence of the bleeding was significantly lower in the bivalirudin group than in the UFH group(5.6% (2/36) vs. 23.7% (9/38) , P=0.028).The incidence of no-reflow/slow flow was also significantly lower in the bivalirudin group than in the UFH group(0 vs. 15.8% (6/38) , P=0.025). There was no significant difference in the incidence of contact thrombosis between bivalirudin group and UFH group(8.3% (3/36) vs. 0, P=0.110). There was no cardiac death or non-fatal myocardial infarction in the 2 groups within 1 year after PCI, and there was no significant difference in the incidence of MACE in 1 year follow-up after operation between bivalirudin group and UFH group (11.1% (4/36) vs. 21.1% (8/38) , P=0.246). @*Conclusion@#The application of the anticoagulant bivalirudin during PCI in patients with CTO lesion can reduce the incidence of perioperative bleeding and no-reflow/slow flow, and does not increase the risk of MACE within 1 year after PCI.
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Objective To evaluate the efficacy of the ratio of the fetal cardiac diameter to biparietal diameter( CBR) as a predictor of homozygous α-thalassemia-1 . Methods Single mid-pregnancies ( 15-22weeks) at risk of homozygous α-thalassemia-1 were enrolled . A total of 251 singleton pregnancies were recruited ,in which 63 cases were homozygous α-thalassemia-1 fetuses and the rest were unaffected . The CBR and cardiothoracic ratio(CTR) were measured by two-dimensional ultrasound . Then the accuracy of these variables were analyzed and compared with each other by ROC curves . Results ①The CBR and CTR in affected fetuses were significantly higher than those in the unaffected( P ＜0 .01) . ②With CBR＞0 .43 and CTR ＞ 0 .52 as the best cut off values ,the sensitivity and specificity of predicting homozygous α-thalassemia-1 fetuses in 15-22 gestational weeks were 95 .74% , 92 .06% and 94 .15% , 85 .71% , respectively ;the area under ROC curve were compared with Z test and there was no significant difference between them ( Z ＝ 1 .500 , P ＝ 0 .1335) . ③ When CBR and CTR were combined ,the sensitivity and specificity of the prediction were significantly increased ( the sensitivity of series experiment : 99 .75% ,the specificity of parallel experiment : 98 .87% ) . Conclusions CBR is a novel , effective and noninvasive predictor of homozygous α-thalassemia-1 in mid-pregnancy whose prediction efficiency is the same as traditional CTR . The measurement of CBR is easier to standardize and is not affected by thoracic lesions such as pleural cavity ,pericardial effusion and skeletal dysplasia . If combined with CTR ,it may play an important role in improving the prenatal detection rate of homozygous α-thalassemia-1 fetuses .
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Objective To investigate the influences of interleukin 17A gene promoter -152G/A (IL-17A -152G/A) and interleukin 17F gene exon 7488 T/C (IL-17F 7488T/C) single nucleotide poly-morphisms on children bronchial asthma and serum total IgE ( TIgE) levels. Methods Genotype distribu-tion of IL-17A-152G/A and IL-17F 7488T/C in 224 children with asthma and 150 healthy subjects was de-tected by polymerase chain reaction-restriction fragment length polymorphism ( PCR-RFLP) analysis. Some samples were selected for PCR product sequencing and verification. IMMAGE800 specific protein analyzer from the Beckman Coulter test system was used to automatically detect serum TIgE levels in all subjects. Re-sults Three genotypes of AA, AG and GG were detected at IL-17A -152G/A locus in both asthma and control groups. Differences in genotype frequency distribution were statistically significant between the two groups (P<0. 05). Subjects carrying the variant allele A at IL-17A-152G/A locus were more likely to have asthma than those without (P<0. 05). Three genotypes of TT, TC and CC were detected at IL-17F 7488T/C locus in both asthma and control groups, but differences in the frequency distribution of genotype and al-lele were statistically significant between the two groups (P<0. 05). There was a significant difference in se-rum TIgE levels between asthma and control groups (P<0. 05). In asthma group, patients of AA genotype at IL-17A -152G/A locus had higher serum TIgE levels than those of AG genotype (P=0. 001) and GG geno-type (P=0. 001). No significant difference in serum TIgE levels was found among healthy subjects of the three genotypes in control group. No significant difference in serum TIgE levels was observed among the sub-jects of TT, TC and CC genotypes at IL-17F 7488T/C locus in asthma or control group (P>0. 05). Conclu-sion IL-17 gene polymorphism was correlated with the incidence of asthma in children in Guiyang area. IL-17A -152G/A polymorphism was an important candidate gene for asthma in Guiyang area and the variant al-lele A at -152G/A locus was correlated with increased serum TIgE levels. IL-17F 7488T/C polymorphism was also an important candidate gene for asthma in Guiyang. Children carrying the variant allele C at IL-17F 7488T/C locus showed a lower risk for asthma in Guiyang. IL-17F 7488T/C polymorphism had no influence on serum TIgE levels.
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Objective:To assess the clinical value of ultrasonic imaging in combination with McGill thyroid nodules score (MTNS) system in differential diagnosis of nodule size and benign and malignant tumors.Methods: The clinical data of a total of 112 patients with thyroid nodules were analyzed retrospectively. The nidus of the patients was identified by ultrasound-guided fine needle aspiration biopsy, and then the MTNS, nodule size and false negative rate of the patients were calculated, respectively.Results: The MTNS of the 112 cases of patients with thyroid nodules was within the range of 1 to 18, with an average score of (6.83±2.31). 16 cases with malignant nodules(the percent was 14.29%) were finally diagnosed by pathology, and 96 cases were diagnosed with benign nodules(the percent was 85.71%). The MTNS of patients with malignant nodules was significantly higher than that of those with benign nodules. Ultrasonic imaging showed that the nodule diameter was within the range of 1 to 8.9cm, with an average diameter of (4.13±4.13)cm. MTNS was positively correlation with nodule diameter (r=0.146,P<0.05). Besides, the average diameter of benign nodules was (3.67±1.60)cm, and that of malignant nodules was (4.23±1.51)cm. The missed diagnosed malignant nodules mainly were large diameter nodules.Conclusion: Ultrasound imaging in combination with MTNS can better predict the benign or malignant risk of thyroid nodules.