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【Objective】 To prepare positron emission computed tomography (PET) molecular probes targeting macrophages using Nb119 and BCⅡ10 labeled with 68Ga nuclide. 【Methods】 To explore the labeling conditions of nanobodies with 68Ga nuclides, first, the anti-Vsig4 nanobody Nb119 and isotype control antibody BCⅡ10 were incubated with NOTA and then purified to obtain the chelating agent-modified NOTA-Nb119 and NOTA-BCⅡ10. The NOTA-Nb119 and NOTA-BCⅡ10 were further incubated with 68Ga. Finally, NOTA-Nb119 was identified by SDS-PAGE and MALDI-TOF methods, and the radiochemical purity was detected by radio-HPLC. 【Results】 The results of SDS-PAGE showed that the lanes of the successfully labeled NOTA-Nb119 had apparent hysteresis than the unlabeled nanobody band, which proved that the molecular weight of the labeled product was increased and NOTA successfully modified the nanobody. Subsequently, 68Ga nuclides could successfully label Nb119 and BCⅡ10. According to radio-HPLC detection, the radiochemical purity of NOTA-Nb119 and NOTA-BCⅡ10 labeled with 68Ga was greater than 90% and remained stable. 【Conclusion】 68Ga-labeled nanobodies have high radiochemical purity and high stability, indicating that this study can be applied to other nanobodies for modification and labeling and provides a practical and feasible method for the preparation of PET using nanobodies.
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Objective:To evaluate the effect of different superficial vascular patterns on pregnancy outcome and residual anastomosis following laser coagulation in placentae with twin-to-twin transfusion syndrome (TTTS).Methods:This study retrospectively collected and analyzed the clinical data and postnatal placenta perfusion characteristics of 57 cases of TTTS who received fetoscopic laser occlusion of chorioangiopagous vessels (FLOC) and delivered at Peking University Third Hospital from April 2014 to April 2019. According to the vascular pattern, all the cases are divided into four groups, which were parallel, staggered, mixed, and monoamniotic groups. Differences in the operation time and method, pregnancy outcome, and residual vascular anastomosis between the four groups were compared using analysis of variance, non-parametric tests, and Chi-square (or Fisher's exact) tests. Results:Among the 57 cases, the staggered, mixed, parallel, and monoamniotic types were accounted for 68.4%(39/57), 15.8%(19/57), 14.0%(8/57), and 1.7%(1/57), respectively. After exclusion of one case of monoamniotic type, gestational weeks at onset and surgery in the parallel group were both later than the staggered and mixed groups [23.0 (22.0-26.3) weeks vs 21.0 (17.0-24.7) weeks and 22.6 (21.3-23.9) weeks, H=10.306, P=0.006; 25.0 (22.6-26.3) weeks vs 22.0 (17.4-24.9) weeks and 23.2 (22.4-24.0) weeks, H=9.926, P=0.007; all P'<0.016 7]. There was no statistical significance in the differences in operation time and method, gestational age at the end of the pregnancy, neonatal birth weight, or birth weight discordance between the three groups. The diameter of residual vascular anastomosis of women in the staggered group was less than that in the mixed group [0.6 (0.1-5.0) mm vs 1.4 (0.3-5.1) mm, P'<0.016 7], but no significant difference was observed in the parallel-group [0.9 (0.2-3.6) mm] neither with the mixed or staggered group. The staggered group was noted for an increased distance ratio of umbilical cord insertion compared with the parallel and the mixed group [0.66 (0.59-1.00) vs 0.49 (0.25-0.55) and 0.48 (0.42-0.53); P'<0.016 7]. There was no significant difference between the parallel and the mixed groups. Conclusions:Placental superficial vascular patterns may affect the residual vascular anastomosis in women with TTTS following FLOC, which should be thoroughly evaluated before the operation to develop an individual management plan to reduce residual anastomosis incidence.
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Objective:To investigate the effect of placental vascular distribution on residual anastomoses (RA) after fetoscopic laser occlusion of chorioangiopagous ressels (FLOC) for twin to twin transfusion syndrome (TTTS).Methods:A total of 57 cases of TTTS after laser surgery were retrospectively analyzed from April 2014 to April 2019 in Peking University Third Hospital. The patients were divided into RA group (24 cases) and non-RA group (33 cases) according to whether RA occurred in the placenta after laser surgery. The clinical characteristics, perioperative conditions, pregnancy outcomes and placental structure characteristics of the two groups were compared. Multivariate logistic regression was used to analyze the risk factors of placental vascular distribution for RA. The RA group was further divided into non-remission group and remission group, and the placental characteristics and pregnancy outcome of the two groups were compared.Results:(1)General clinical characteristics: the age, application of assisted reproductive technology, incidence of gestational hypertension, gestational diabetes mellitus, preoperative maximum amniotic fluid depth of the donor and recipient twins, Quintero stage and placental position of TTTS patients in the two groups were compared respectively, and there were no statistically significant differences (all P>0.05).The gestational age of patients received FLOC in the RA group was significantly higher than the non-RA group [(23.0±2.4) vs (21.9±2.7) weeks, P=0.033].(2) Perioperative conditions and pregnancy outcomes: the delivery gestational age of the RA group was significantly lower than that of the non-RA group (median:31.8 vs 34.4 weeks, P=0.002);The newborn birth weight in the RA group was significantly lower than that in the non-RA group [(1 648±597) and (2 013±481) g, P=0.003].The birthweight difference in the RA group was significantly higher than that in the non-RA group (median:0.30 vs 0.11, P=0.005). (3) The placental structure and the risk factors influencing RA happened: the differences in the proportion of four types of placental vascular distribution in the RA group and non-RA group were different significantly ( χ2 =10.214, P=0.012), with a detail of parallel type 29% (7/24) and 3% (1/33), staggered type 58% (14/24) and 76% (25/33), hybrid 8% (2/24) and 21% (7/33), monoamniotic membrane type 4% (1/24) and 0 respectively. Multivariate logistic regression analysis showed that parallel placental vascular distribution was an independent risk factor for RA after FLOC ( OR=24.5, 95% CI 1.7-336.2, P=0.017). (4) Placental characteristics and pregnancy outcomes in the remission and non-remission groups of the RA group: the incidence of three kinds of anastomoses, the total number, total diameter and proportion of RA, and the placental territory discordance ratio were compared between the two groups, and there were no statistical significances ( P>0.05);The birth weight difference ratio in the non-remission group was higher than that in the remission group (median:0.41 vs 0.28, P=0.036). Conclusion:The parallel type of placental vascular distribution may be an independent risk factor for RA in TTTS after laser surgery.
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Objective To evaluate the efficacy of fetoscopic laser occlusion of chorioangiopagous vessels (FLOC) in treatment of twin-twin transfusion syndrome (TTTS) and to investigate the incidence of TTTS complicated with selective intrauterine growth restriction (sIUGR) for better understanding the effects of sIUGR as a complication of TTTS on pregnancy outcomes. Methods A retrospective study was performed on 116 gravidas who were diagnosed with TTTS of Quintero stage Ⅰ - Ⅳ in Peking University Third Hospital from September 2008 to September 2014. Among them, 44 cases received FLOC therapy. The incidences of sIUGR in each Quintero stage of TTTS were analyzed. Pregnancy outcomes of those 44 cases treated with FLOC were observed and the differences among four stage groups were analyzed. Chi-square or Fisher exact test was performed for statistical analysis. Results (1) The survival rates of both twins from stage Ⅰ to Ⅳ groups were 4/7, 10/14, 5/19 and 3/4, respectively, with statistically significant difference (χ2=7.840, P=0.038), but that in stage Ⅲ group was lower than in stage Ⅱ group without significant difference (P'=0.008). Differences in the total fetal survival rate among the four groups were statistically significant [8/14, 75% (21/28), 32% (12/38) and 6/8, χ2=14.016, P=0.002]. The total fetal survival rate in stage Ⅲ group was significantly lower than that in stageⅡ group (P'<0.008). In patients with stage Ⅲ TTTS, those complicated with sIUGR, after receiving FLOC therapy, showed a lower total fetal survival rate than those without sIUGR [21% (6/28) vs 6/10, P<0.05]. (2) Among the 116 TTTS patients, there were 63 cases (54%) with sIUGR complication. Patients with sIUGR complication in TTTS stages Ⅰ to Ⅳ groups accounted for 40% (14/35), 48% (11/23), 78% (28/36) and 46% (10/22), respectively, and the differences were significant (χ2=11.963,P=0.007). The incidence of sIUGR in stage Ⅲ group was greater than that in stage Ⅰ group (χ2=10.482, P'=0.002), and those in both stage Ⅲ and Ⅱ groups were higher than in stage Ⅰgroup without significant difference. Conclusions TTTS patients in stage Ⅲ have lower survival rate of both twins and total fetal survival rates after FLOC therapy, which may be related to a higher incidence of concurrent sIUGR.
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Objective To investigate the clinical outcome and placental characteristics of spontaneous twin anemia-polycythemia sequence (sTAPS). Methods Twelve cases with sTAPS delivered in Peking University Third Hospital from May 2013 to August 2016. The data of ultrasound characteristics, gestational age at delivery, and 1 minute Apgar score were analyzed,retrospectively. Placental superficial vascular anastomoses, placental territory discordance and the ratio of umbilical cords insertion distance to the longest placental diameter were also analyzed. Results (1) Only 1 case of sTAPS was diagnosed prenatally, the others were diagnosed postnatally because the fetal middle cerebral artery(MCA) doppler was not measured regularly. Five cases were complicated with selective intrauterine growth restriction (sIUGR). The median gestational age at delivery was 32.8 weeks(31-37 weeks). The pregnancies were terminated because 3 cases were sIUGR typeⅠ, 1 case was sIUGR type Ⅱ, 1 case was sIUGR type Ⅲ, 2 cases were fetal distress, 2 cases were severe pre-eclampsia, 2 cases were premature rupture of membrane, 1 case was fetal hydrops with abnormal doppler waveforms of ductus venouses. (2) When 5 sIUGR cases were excluded, there was no difference between the twins in birth weight [1797 g(940-2620 g),1648 g(980-2500 g);P=0.688]. The hemoglobin (Hb) level in all donor was significantly lower than recipient(P=0.000)and the inter-twin Hb difference was 147.6 g/L (84.0-216.0 g/L). While the reticulocyte percentage in donor was significantly higher than recipient (P=0.013) and reticulocyte percentage ratio was 3.60 (1.04-7.50). Five donor newborns had neonatal asphyxia, including 1 severe asphyxia, while no asphyxia happened in the recipient twins. (3) Arterio-arterial (A-A) anastomoses, veno-venous (V-V) anastomoses, arterio-venous (A-V) anastomoses were found in 3, 1 and 11 placentas, respectively. The total number of anastomoses was 2 (1-5) and the total diameter was 1.1 mm (0.4-2.1 mm), including 0 (0-1) A-A anastomoses with 0.2 mm (0.0-0.9 mm) in diameter and 2 (0-5) A-V anastomoses with 0.7 mm (0.0-2.1 mm) in diameter. The placental territory discordance was 0.17 (0.02-0.40) and the ratio of umbilical cords insertion to the longest placental diameter was 0.82 (0.34-0.99). Conclusions The pathogenesis of sTAPS might result from slow and chronic blood transfusion from donor to recipient through a few minuscule vascular anastomoses in the placenta. In all monochorionic twins, especially sIUGR cases, MCA doppler should be monitored closely in the second and third trimester, in order to diagnose and manage sTAPS in time.