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Objective:To analyze the effects of selective feticide by radiofrequency ablation (RFA) and the risk factors for adverse pregnancy outcomes in twins complicated by selective intrauterine growth restriction (sIUGR) and evaluate the neurodevelopment in live births during a short-term follow-up.Methods:This study retrospectively enrolled 75 twins with sIUGR who underwent RFA for selective feticide and were delivered in the First Affiliated Hospital of Sun Yat-sen University between January 1, 2017 and March 31, 2022. According to the gestational age at the procedure, they were divided into three groups including 16-19 +6 weeks of gestation (Group A, n=16), 20-23 +6 weeks of gestation (Group B, n=44) and ≥24 weeks of gestation (Group C, n=15). They were also grouped according to the presence or absence of twin-twin transfusion syndrome (TTTS): sIUGR with TTTS group ( n=36) and isolated sIUGR group ( n=39). The 39 cases in the isolated sIUGR group were further divided into three groups according to the Doppler flow in the smaller co-twin: type Ⅰ ( n=3), type Ⅱ ( n=27) and type Ⅲ ( n=9). According to pregnancy outcomes, the 75 cases were divided into adverse pregnancy outcome group ( n=49) and non-adverse pregnancy outcome group ( n=26). Statistical analysis was performed using two independent sample t-test, one-way analysis of variance and LSD test, nonparametric test and Nemenyi test, as well as Chi-square test and Fisher's exact test to compare the difference in clinical characteristics and perinatal outcomes among groups. Kaplan-Meier survival curves and Log-rank test were used to analyze the duration of pregnancy after the procedure. Univariate logistic regression analysis was used to identify the risk factors for adverse pregnancy outcomes. Results:(1) The gestational age at the time of procedure was (21.9±2.3) weeks (16.6-26.0 weeks) for all cases. The intertwin estimated fetal weight discordance (ΔEFW) was less and the duration of RFA was shorter in group A than in group B or C [(27.8±8.4)% vs (36.2±12.0)% and (39.8±15.5)%; 7 min (5-14 min) vs 10 min (5-16 min) and 12 min (8-18 min); LSD test or Nemenyi test, P<0.017]. The incidence of TTTS was higher in group A than in group B or C [12/16 vs 43% (19/44) and 5/15; Bonferroni correction, P<0.017]. There was no significant difference in the incidence of premature rupture of membrane, spontaneous abortion, fetal demise, premature delivery and gestational age at delivery between Group A, B and C (all P>0.05). (2) Compared with the isolated sIUGR group, the sIUGR with TTTS group showed less ΔEFW [(29.6±11.4)% vs (40.1±11.8)%, t=3.88, P<0.001], higher incidence of premature rupture of membrane [47% (17/36) vs 21% (8/39), χ2=6.01, P=0.014], lower rate of live births [69% (25/36) vs 95%(37/39), χ2=8.45, P=0.004] and earlier delivery [34.1 weeks (26.7-40.7 weeks) vs 38.0 weeks (29.3-40.0 weeks), Z=311.50, P=0.018]. (3) There was no significant difference in the incidence of premature rupture of membrane, live birth rate or 30-day survival rate among the sIUGR type Ⅰ, Ⅱ and Ⅲ groups (all P>0.05). (4) sIUGR complicated by TTTS was a risk factor for adverse pregnancy outcomes of the co-twin after the procedure ( OR=3.94, 95% CI: 1.40-11.10, P=0.010). (5) Thirteen co-twins presented with cardiac enlargement, myocardial hypertrophy or/and tricuspid regurgitation in routine ultrasound scans before the procedure and nine of them had TTTS. Among them, eight live births were followed up for one month to 4.5 years of age and no abnormality in cardiac function was reported. (6) There were overall 62 live births. Apart from two cases of neonatal death and four lost to follow-up, the other 56 cases were followed up to one month to 5 years of age and two premature infants showed gross motor retardation. Conclusions:The gestational age at RFA has no significant impact on pregnancy outcomes, while sIUGR complicated by TTTS may increase the risk of adverse outcomes after the procedure. After RFA, the overall survival rate of the co-twin in pregnancies with sIUGR is high and no severe neurodevelopmental abnormalities has been found during a short-term follow-up.
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Objective:To investigate the performance of chromosome karyotype, chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) in prenatal diagnosis of true fetal chromosome mosaicism. Methods:This retrospective study enrolled 40 women with true fetal chromosome mosaicism from 4 071 singleton pregnant women who were indicated for and underwent amniocentesis or/and cordocentesis in the the First Affiliated Hospital of Sun Yat-sen University from April 2018 to August 2021. The results of chromosome karyotyping, CMA and FISH, the types of chromosomal mosaicism, mosaicism ratio and pregnancy outcomes were analyzed using Chi-square test. Results:(1) The detection rate of true fetal mosaicism was 0.98% (40/4 071). (2) Sex chromosome mosaicism accounted for 42.5% (17/40). Other chromosomal mosaicism involved chromosomes 21, 22, 18, 16, 7, 12, 15, 17 and 20, as well as balanced chromosomal translocation. (3) The detection rate of true fetal mosaicism by chromosome karyotyping was 77.4% (24/31) from amniotic fluid samples and 10/19 from umbilical cord blood samples, while that data by CMA was 76.7% (23/30) and 7/11,respectively. (4) Of the 40 pregnant women with fetal chromosome mosaicism, FISH test was performed on 20 cases (14 cases were verified with both amniotic fluid and umbilical cord blood samples, five with amniotic fluid samples and one with umbilical cord blood sample), and all of the diagnosis of mosaicism were confirmed. For those with mosaicism ratio <30%, the detection rate by FISH was higher than that by CMA among amniotic fluid samples [14/19 vs 43.5% (10/23), χ2=3.88, P=0.049]. (5) Among the 40 pregnant women, five were lost to follow-up; 18 chose to terminate the pregnancy; and 17 continued the pregnancy to delivery. No abnormalities in mental or physical development were reported in the 17 neonates after birth or during on-line follow-up between 6 to 24 months old. Of the 14 pregnant women with mosaicism ratio <30% which confirmed by FISH, eight chose to continue the pregnancy, and no abnormalities in mental development or growth were found in the neonates. Conclusions:In prenatal diagnosis of true fetal choromosome mosaicism, the incidence of sex chromosome mosaicism is the highest. FISH may improve the prenatal diagnosis rate of mosaicism and is more accurate in determining the mosaicism ratio. The combination of FISH, CMA and chromosome karyotyping would significantly improve the detection rate of chromosomal mosaicism and assess the mosaicism ratio more accurately, which is of great value in clinical consultation and evaluation of fetal prognosis.
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Objective:To investigate the prenatal genetic features and the factors influencing the prognosis of twin reversed arterial perfusion sequence (TRAPS) in monochorionic twin pregnancies.Methods:A total of 99 cases diagnosed with TRAPS by prenatal ultrasound in the First Affiliated Hospital of Sun Yat-sen University from July 1, 2007, to December 31, 2021, were included retrospectively. The prenatal genetic features of acardiac and pump twins were analyzed. Eighty-nine cases were followed up and divided into two groups: the expectation group ( n=45) and the intrauterine intervention group (all underwent radiofrequency ablation, n=44) and the pregnancy outcomes were compared between the two groups. After excluding eight cases without complete ultrasound data, the expectation group was further divided into two subgroups: the pump fetus survival ( n=28) and the pump fetus death groups ( n=9), and the survival subgroup was divided into the spontaneous arrest group ( n=16) and coexistence group ( n=12) according to whether or not the blood flow stopped spontaneously.The relationship between ultrasonic indexes and pregnancy outcome was compared between the groups. Chi-square test (or Fisher's exact test), univariate logistic regression analysis and receiver operating characteristic (ROC) curve were used to analyze the relationship between the estimated acardiac to pump twin weight ratio (A/P Wt) and the pregnancy outcome of the pump twin in the expectation group. Results:(1) The median gestational age at diagnosis of the 99 TRAPS cases was 16.4 weeks (13.3- 21.3 weeks) and 32% (32/99) were diagnosed in the first trimester. Most of the cases were monochorionic diamniotic pregnancies (72/99, 73%). The survival rate of the pump twins was 71% (63/89). (2) Chromosome karyotyping and/or chromosomal microarray analysis was performed in 19 acardiac twins and 82 pump twins. The detection rate of genetic abnormalities in the acardiac twins was higher than that in the pump twins [4/19 vs 5% (4/82), Fisher's exact test, P=0.039]. Chromosomal microarray analysis was performed in 54 pump twins with normal karyotypes and the results showed three (6%) with genetic abnormalities. (3) In the expectation group, the area under ROC curve for the prenatal A/P Wt were 0.913 in predicting pump twin death and 0.807 in predicting spontaneous cessation of blood flow in the cardiac twin, and the cut-off values were 0.24 (sensitivity: 88.9%, specificity: 96.4%) and 0.11 (sensitivity: 75.0%, specificity: 81.3%), respectively. The survival rate of pump twins with abnormal cardiac function after intrauterine intervention was higher than that of the expectant group [72% (18/25) vs 3/11, Fisher's exact test, P=0.025]. Conclusions:TRAPS can be diagnosed in the first trimester and commonly occur in monochorionic diamniotic pregnancies. The detection rate of genetic abnormalities in the acardiac twins is higher than that in the pump twins. Prenatal A/P Wt>0.24 indicates the death of the pump twin and prenatal A/P Wt≤0.11 suggests a high possibility of spontaneous cessation of blood flow in the acardiac twin. Radiofrequency ablation is an effective method for improving the prognosis of the pump twin with cardiac dysfunction.
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Remodeling the tumor microenvironment through reprogramming tumor-associated macrophages (TAMs) and increasing the immunogenicity of tumors via immunogenic cell death (ICD) have been emerging as promising anticancer immunotherapy strategies. However, the heterogeneous distribution of TAMs in tumor tissues and the heterogeneity of the tumor cells make the immune activation challenging. To overcome these dilemmas, a hybrid bacterium with tumor targeting and penetration, TAM polarization, and photothermal conversion capabilities is developed for improving antitumor immunotherapy in vivo. The hybrid bacteria (B.b@QDs) are prepared by loading Ag2S quantum dots (QDs) on the Bifidobacterium bifidum (B.b) through electrostatic interactions. The hybrid bacteria with hypoxia targeting ability can effectively accumulate and penetrate the tumor tissues, enabling the B.b to fully contact with the TAMs and mediate their polarization toward M1 phenotype to reverse the immunosuppressive tumor microenvironment. It also enables to overcome the intratumoral heterogeneity and obtain abundant tumor-associated antigens by coupling tumor penetration of the B.b with photothermal effect of the QDs, resulting in an enhanced immune effect. This strategy that combines B.b-triggered TAM polarization and QD-induced ICD achieved a remarkable inhibition of tumor growth in orthotopic breast cancer.
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Background and purpose:Epidermal growth factor receptor (EGFR) gene mutation is the most important predictive factor for determining the effectiveness of EGFR tyrosine kinase inhibitors (TKIs) for non-small cell lung cancer (NSCLC). This study aimed to determine the clinical application value of mutation-speciifc immu-nohistochemistry forEGFR mutation detection in NSCLC.Methods:Mutation-specific immunohistochemistry and ampliifcation refractory mutation system (ARMS) were used simultaneously to detectEGFR gene mutation status in 290 lung cancer specimens. The sensitivity, speciifcity, positive predictive value (PPV) and negative predictive value (NPV) of mutation-speciifc immunohistochemistry for detectingEGFR gene mutations were evaluated. The consistency was analyzed between mutation-speciifc immunohistochemistry results and ARMS results.Results:With ARMS testing as the gold standard, when a cutoff value of score 1+ was used as positive by immunohistochemistry, the sensitivity of mutation-speciifc immunohistochemistry forEGFR gene mutation was 72.92%, speciifcity 95.20%, positive predictive value 93.75% and negative predictive value 78.08%. The accuracy of immunohistochemistry was obviously different when variousEGFR gene mutations were detected. The sensitivity of immunohistochemistry for exon 19 deletion was only 55.55%, but speciifcity was above 99%. When immunohistochemistry score was 1+, the sensitivity for L858R mu-tation was 90.27%, whereas speciifcity was 95.86%. When immunohistochemistry score was 2+ or 3+, the speciifcity for L858R mutation was 98.63%-100%. The results of mutation-speciifc immunohistochemistry were ifnely correlated with mutation status determined by ARMS assay (P<0.001, Kappa value: 0.612-0.864). Mutation-speciifc immunohis-tochemistry can directly determineEGFR gene mutation abundance at the cellular level.Conclusion:Mutation-speciifc immunohistochemistry could be an effective supplemental method toEGFR molecular tests.
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Objective To compare the differences between two statistical methods for evaluating non-sensitivity of pathogenic bacteria to antimicrobial agents,and explore effect of non-consideration of clinical background on evalua-ting extent of bacterial resistance.Methods Data of Staphylococcus aureus and Acinetobacter spp .in a hospital in the first half year of 2008,2010 and 2013 were collected and conducted statistical analysis with two methods (me-thod 1 :based on all clinically isolated bacteria;method 2 :based on infection-related non-repetitive bacteria),two methods for evaluating bacterial non-sensitive rates to antimicrobial agents were compared.Results The non-sensi-tive rates of Acinetobacter spp .to various antimicrobial agents :statistical results by using method 1 were generally higher than those using method 2,absolute difference between two statistical methods was 10.46%-33.77%;the non-sensitive rates of Staphylococcus aureus to various antimicrobial agents :except compound sulfamethoxazole in 2010 and 2013(difference were 6.17% and 10.21 % respectively),penicillin G (difference was 3.86%),erythromy-cin (difference was 2.71 %),and azithromycin in 2013 (difference was 2.43%),statistical results by using method 1 were generally higher than those using method 2,absolute difference between two statistical methods was 0-18.04%.Conclusion There are deviation in the non-sensitive rates of bacterial strains to antimicrobial agents by using two different statistical methods,deviation is larger in Acinetobacter spp ..The resistance level might be incorrectly higher when evaluating the resistance status without considering clinical background of bacteria.
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each group were sacrificed, respectively. Distributions of BrdU positive cels and ChAT positive cels were detected by S-P immunohistochemical method. The learning and memory abilities of rats were detected by Morris water maze system. RESULTS AND CONCLUSION:BrdU positive cels were mainly distributed in the cortex and hippocampus, especialy around the blood vessels, and there was the presence of focal aggregation. A smal amount of BrdU positive cels were observed in the basal ganglia and thalamus as wel as in the ependyma. BrdU positive cels were counted at different time after operation. The number of BrdU positive cels decreased with time, and only a smal number of BrdU positive cels were observed at 60 days after transplantation. The number of ChAT positive cels at different time after transplantation was ranked as folows: neural stem cel transplantation group > model group > sham operated group (P < 0.05). Compared with the model group, the time for searching the platform was significantly lower in the neural stem transplantation group and sham operated group, but the number of crossing the platform was significantly higher in the neural stem cel transplantation group and sham operated group (P < 0.05). The results show that neural stem cels could be transplanted into the rats with vascular dementia, and the cels could survive and migrate in the brain of rats and significantly improve the learning and memory ability. This mechanism may be related to the differentiation and growth of cholinergic neurons in the hippocampus.
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Objective To study the resistance and molecular profiles of Staphylococcus aureus strains isolated from the clinical specimens.Methods Antimicrobial susceptibility was tested with 56 strains of Staphylococcus aureus isolated from a hospital from May to November 2011.The mecA and pvl genes were detected.The spa genetic types were analyzed.Results A total of 21 (37.5%)Staphylococcus aureus strains were resistant to methicillin (MRSA)and 35 (62.5%)were sensitive to methicillin (MSSA).Nineteen of the 21 (90.5%)MRSA strains carried mecA gene.Compared with MSSA,MRSA were much less sen-sitive to rifampin,fluoroqunolones,tetracycline and gentamicin (P <0.05).All the MRSA isolates were susceptible to vanco-mycin,linezolid,tigecycline,quinupristin-dalfopristin and nitrofurantoin.Six spa types were identified among the MRSA strains.Type t030 was the most prevalent,accounting for 66.7% (14/21)of all the MRSA strains.MRSA-t030 and MRSA-t002 were resistant to multiple antibiotics.Eighteen spa types were identified among the MSSA strains.Type t189,t377 and t034 were the top three spa types of MSSA,accounting for 14.3%,14.3% and 11.4%,respectively.A new MSSA spa typ-ing strain new1 was isolated from pus.There were five Panton-Valentine leukocidin (PVL)-positive isolates,3 of which was MSSA-t189 type. Conclusions Type t030 is the most prevalent spa type among clinical MRSA strains,which is resistant to many kinds of antibiotics and widely spreads in the hospital setting.There are many different spa types a-mong the MSSA strains.Type t389,t377 and t034 are the top three spa types of MSSA.