Objective To investigate the correlation between the level of oxidative stress indicators in placental tissues and placental perfusion level in twin-to-twin transfusion syndrome (TTTS). Methods A total of 105 cases of dichorionic monoamniotic monozygotic twin pregnant women were included in the study. They were divided into control group of 90 cases and observation group of 15 cases based on whether TTTS occurred during pregnancy. The levels of oxidative stress indicators[malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX)]in placental tissues below the attachment points of the two umbilical cords in the two groups were detected. The maximum diameters of arterio-arterial (AA) anastomosis, veno-venous (VV) anastomosis, and arterio-venous (AV) anastomosis, as well as the difference ratio of placental tissue areas (PTD), were compared between the two groups. The correlation between the levels of oxidative stress indicators in placental tissues and placental perfusion level was analyzed. Results Compared with placental A and placental B in the control group, the MDA level in the placental tissues of the blood supply end and the blood recipient end in the observation group was increased, while the SOD and GSH-PX levels were decreased, and the maximum diameter of AA anastomosis was reduced, there were statistically significant differences (P < 0.05). In the observation group, the MDA level in the placental tissues of the blood supply end was higher than that of the blood recipient end, the SOD and GSH-PX levels were lower than those of the blood recipient end, and the maximum diameter of AA anastomosis was smaller than that of the blood recipient end, with statistically significant differences (P < 0.05). The maximum diameters of AV anastomosis and PTD in the observation group were larger than those in the control group (P < 0.05). There was no significant difference in the maximum diameter of VV anastomosis between the two groups (P>0.05). Pearson correlation analysis showed that there were no significant correlations of MDA, SOD and GSH-PX levels with the maximum diameter of AA anastomosis and PTD in the placental tissues of the control group (P>0.05).In the placental tissues of the blood supply end and the blood recipient end in the observation group, MDA levels showed a strong negative correlation with the maximum diameter of AA anastomosis and a strong positive correlation with the maximum diameter of AV anastomosis and PTD (P < 0.05). SOD and GSH-PX levels showed strong positive correlations with the maximum diameter of AA anastomosis and strong negative correlations with the maximum diamete of AV anastomosis and PTD (P < 0.05). Conclusion There is a significant imbalance of oxidative stress in placental tissues of TTTS pregnant women, and the decrease in antioxidant activity of placental tissues may be an important cause of placental perfusion injury.

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.

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.

Objective:To explore the possible factors leading to failure of cell-free DNA (cfDNA) testing in maternal peripheral blood and analyze the pregnancy outcomes of this group of pregnant women.Methods:This retrospective study involved 5 195 women who underwent cfDNA testing in Peking University Third Hospital from April 2017 to April 2019. Based on the first cfDNA testing results, clinical characteristics of the pregnant women with successful (success group, n=5 107) and failed (failure group, n=88) cfDNA testing were compared using Mann-Whitney U test and Chi-square test. Multivariate logistic regression was used to analyze the risk factors of cfDNA testing failure and the effect of body mass index (BMI) on the success rate, and evaluate the feasibility of re-sampling and the factors affecting the unsuccessful testing of a second sample. Results:The failure rate of first cfDNA testing was 1.7% (88/5 195). Successful cfDNA testing was achieved in 74 (87.1%, 74/85) of 85 re-sampling cases, while results of the other 11 cases (12.9%, 11/85) remained invalid. Thus, the final failure rate was 0.2% (11/5 195). Multivariate logistic regression revealed that increased maternal age ( OR=1.086, 95% CI: 1.023-1.152, P=0.006), BMI ( OR=1.083, 95% CI: 1.021-1.149, P=0.008) and twin pregnancies ( OR=3.093, 95% CI: 1.715-5.577, P<0.001) were the risk factors of cfDNA testing failure, while increased cell-free fetal DNA (cffDNA) concentration ( OR=0.758, 95% CI: 0.720-0.761, P<0.001) was a protective factor. The overweight (BMI: 25-29.9 kg/m 2) and obese (BMI≥30 kg/m 2) women were 3.626 ( OR=3.626, 95% CI: 2.298-5.724, P<0.001) and 4.064 ( OR=4.064, 95% CI: 1.779-9.284, P=0.001) times more likely to have failed cfDNA testing than those with normal weight (BMI: 18.5-24.9 kg/m 2), respectively. The success rate of re-testing decreased as the maternal BMI increased, regardless of the time interval between the two samplings ( OR=0.840, 95% CI: 0.699-1.245, P=0.065). Seven out of the 74 cases with successful results in re-testing were at high risk, including one 45,X and one 47,XXY, confirmed by karyotyping amniocentesis. Among the 11 pregnant women with a failed testing after second sampling, eight underwent prenatal diagnosis with normal fetal chromosome karyotypes, and the other three cases without prenatal diagnosis all gave birth to neonates with normal phenotype. There was no statistical difference in the incidence of pregnancy loss between the failure and success group [9.1% (8/88) vs 2.5% (128/5 107), P=0.090]. Conclusions:Pregnant women with advanced age and higher BMI, lower cffDNA fraction and twin pregnancies are more likely to fail in cfDNA testing. For obese women, blood sampling can be postponed to a larger gestational age to reduce the failure rate. For pregnant women with failed testing in first sampling, a re-sampling is recommended, moreover, prenatal diagnosis is necessary for those had high-risk results or failed in re-testing.

Objective: To explore the effect of PDCA nursing model combined with token reward on the compliance and negative emotions of children with hypospadias. Methods: A total of 120 children with hypospadias who were admitted to Children′s hospital affiliated to Zhengzhou University from February 2017 to December 2017 were selected as study subjects. According to the time of admission, they were divided into observation group and control group, with 60 cases in each group. The control group was given routine nursing care, the observation group was given PDCA nursing mode combined with token rewards intervention on the basis of routine care. The self-made children's behavioral compliance assessment table was used to compare the compliance of the two groups of children. Achenbach Child Behavior Check List (CBCL) scores were performed before and after the intervention. The hospitalization time and the incidence of complications were calculated. Results: There was no significant difference in CBCL scores between the two groups at admission (t=0.965, P=0.102). The scores of compliance and CBCL scores of the observation group were (43.12±3.99) points and (17.62±7.30) points respectively, the scores of control group were (30.67±4.53), (24.23±6.67), the difference was statistically significant (t=15.977, 5.184, P<0.01). The hospitalization time and complication rate of the observation group were (18.73±0.84)d, 15.00% (9/60), which were significantly lower than (20.92±1.90) d, 31.67% (19/60) of the control group, and the difference was statistically significant (t=8.166, χ²=4.658, P<0.01 or 0.05). Conclusions The PDCA nursing model combined with token reward can improve the compliance of children with hypospadias and improve their negative emotions.

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.

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.

The secretion of melatonin (MT) is obviously different in the younger and the senior sectors of the population, and the maximum plasma concentration of seniors is only half of that in the younger population group. If exogenous MT can be supplied to senior citizens based on the secretion rate and amount of endogenous MT in the younger population by a bio-mimetic drug delivery system (DDS), an improved therapeutic effect and reduced side effects can be expected. Based upon this hypothesis, the pharmacokinetic parameters of MT, namely, the absorption rate constant (k a), the elimination rate constant (k e), and the ratio of absorption rate (F) to the apparent volume of distribution (V) were obtained by a residual method depending on the plasma concentration curve of immediate release preparations in the healthy younger population. The dose-division method was applied to calculate the cumulative release profiles of MT achieved by oral administration of a controlled release drug delivery system (DDS) to generate plasma MT profiles similar to the physiological level-time profiles. The in vivo release of MT deduced from the healthy younger population physiological MT profiles as the pharmacokinetic output of the bio-mimetic DDS showed a two-phase profile with two different zero order release rates, namely, 4.919 μg/h during 0-4 h (r=0.9992), and 11.097 μg/h during 4-12 h (r=0.9886), respectively. Since the osmotic pump type of DDS generally exhibits a good correlation between in vivo and in vitro release behaviors, an osmotic pump controlled delivery system was designed in combination with dry coating technology targeting on the cumulative release characteristics to mimic the physiological MT profiles in the healthy younger population. The high similarity between the experimental drug release profiles and the theoretical profiles (similarity factor f 2>50) and the high correlation between the predicted plasma concentration profiles and the theoretical plasma concentration profiles (r=0.9366, 0.9163, 0.9264) indicated that a prototype bio-mimetic drug delivery system of MT was established. The similarity factors between the experimental drug release profiles and the theoretical release profile were all larger than 50 both in periods of 0-4 h and 4-12 h, namely, 68.8 and 57.3 for the first batch (Batch No. 20131031), 76.7 and 50.2 for the second batch (Batch No. 20131101), and 73.7 and 51.1 for the third batch (Batch No. 20131126), respectively. The correlation coefficients between the predicted plasma concentration profiles based on the release profiles of the bio-mimetic DDS and physiological profiles were 0.9366 (Batch No. 20131031), 0.9163 (Batch No. 20131101), 0.9264 (Batch No. 20131126), respectively. Since the pharmacokinetic profile of MT in any kind of animal differs markedly from that of human beings, it is impossible to test the bio-mimetic DDS in animals directly. Therefore, the predicted pharmacokinetic profile based upon the in vitro release kinetics is an acceptable surrogate for the conventional animal test. In this research, a bio-mimetic DDS for replacement of MT was designed with in silico evaluation.

Objective To explore the clinical value of high risk human papillomavirus(HR-HPV) test in shunting monitoring of atypical squamous cell of undetermined significance (ASCUS) and to seek the best treatment for patients with ASCUS.Methods 470 patients with ASCUS tested by TCT were given HR-HPV testing and biopsy under colposcopy.The clinical characteristics were analyzed.Results 470 cases of ASCUS contained a variety of cervical lesions:inflammation/acuminate accounted for 69.15％ (325/470),cervical intraepithelial neoplasia (CIN)accounted for 29.57％ (139/470),and invasive carcinoma accounted for 1.28％ (6/470).The positive rate of cervical pathological examination was 30.85％ (≥ CIN Ⅰ,145/470).The positive rate of HR-HPV was 50.43％(237/470).The detection rate of ≥CIN Ⅰ in HR-HPV positive group and negative group was 55.27％ (131/237)and 6.01％ (14/233),while the detection rate of ≥ CIN Ⅱ in HR-HPV positive group and negative group was 36.71％ (87/237) and 1.29％ (3/233).The differences were statistically significant(P ＜ 0.01).Incidence of ≥ CIN Ⅰ and invasive carcinoma in HR-HPV positive group was about 19.332 fold of that in HR-HPV negative group(95％ CI =10.632 ～ 35.152),while the incidence of ≥CIN Ⅱ and invasive carcinoma was about 44.467 fold of HR-HPV negative group (95％ CI =13.812 ～ 143.152).The detection sensitivity,specificity,positive predictive value,negative predictive value(NPV) of HR-HPV in the≥ CIN Ⅰ patients were 90.34％,67.38％,61.60％,93.99％.Those of ≥ CIN Ⅱ patients were 96.67％,60.53％,36.71％,98.71％.Conclusion ASCUS included partial CIN of high grades and cervical cancer,and the proportion of HPV infection is large,detection of high risk HPV-DNA is an effective shunting management method of ASCUS.