OBJECTIVE To prepare reactive oxygen species （ROS）-responsive methotrexate （MTX）-modified paclitaxel （PTX）/icariin （ICA） micelles （MTX-oxi-Ms@PTX/ICA）， and perform technology optimization and in vitro anti-tumor effect evaluation. METHODS Synergistic toxicity concentration range of PTX and ICA was screened by synergistic toxicity test. The micelles were prepared by thin film hydration method， and their technology was optimized by response surface methodology. The fundamental characteristics of the micelles prepared by the optimal technology were evaluated. The micelles’ cytotoxicity， targeting ability to renal carcinoma RENCA cells of mice， and their inhibitory effects on invasion and migration were assessed. RESULTS Results of synergistic toxicity experiments demonstrated that the strongest synergistic effect occurred when PTX concentrations ranged from 2.5 to 10 μmol/L and ICA concentrations ranged from 5 to 15 μmol/L. The optimal technology of MTX-oxi-Ms@PTX/ ICA was determined to include 80 mg Soluplus®， Soluplus® and TPGS1000 mass ratio of 4∶1 （mg/mg）， 2 mg DSPE-PEG2000-TK- PEG5000， 2 mg DSPE-PEG2000-MTX， 1 mg PTX， and 1.5 mg ICA， with a hydration temperature of 35 ℃ and a formulation volume of 5 mL. Under the optimal conditions， average encapsulation efficiency of PTX and ICA in 3 batches of MTX-oxi- Ms@PTX/ICA reached 92.75%， the critical micelle concentration （CMC） was 0.007 9 mg/mL， the particle size was （62.09±1.68） nm， the polydispersity index （PDI） was 0.046±0.032， and the Zeta potential was （－2.47±0.15） mV. Within 30 days of placement， there was no significant change E-mail：yingqiang_1126@163.com in particle size and polydispersity index of micelle. In vitro release experiments showed that MTX-oxi-Ms@PTX/ICA released drugs more rapidly in oxidative environments. The half maximal inhibitory concentration of MTX-oxi-Ms@PTX/ICA against RENCA cells was （5.170±0.036） μmol/L. In vitro cellular uptake experiments indicated that compared with unmodified micelles， MTX modified micelles had stronger targeting effects on cancer cells， and also significantly enhanced the inhibitory ability of invasion and migration of RENCA cells （P＜0.05）. CONCLUSIONS MTX-oxi-Ms@PTX/ICA micelles are successfully prepared， which exhibit high encapsulation efficiency， low critical micelle concentration， and good stability. These micelles demonstrate significant cytotoxicity against RENCA cells and effectively inhibit cancer cell invasion and migration.

Objective:To investigate the effect of prenatal dexamethasone on short-term outcomes and long-term neurological development in late preterm infants with twin pregnancy.Methods:A total of 315 pregnant women with twin pregnancy and their preterm infants who delivered in Peking University Third Hospital from January 2019 to December 2022 were retrospectively analyzed. The clinical data of pregnant women and preterm infants were collected. They were divided into non-medication group (93 pregnant women and 186 preterm infants), medication after 34 weeks group (123 pregnant women and 246 preterm infants), and medication before 34 weeks group (99 pregnant women and 198 preterm infants). Short-term outcomes of preterm infants were analyzed, including the incidence of neonatal respiratory distress syndrome (NRDS), wet lung, hypoglycemia, neonatal septicemia, intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD) and neonatal necrotizing enterocolitis (NEC). "Ages and Stages Questionnaire-Third Edition (ASQ-3) scale" was used to follow up the late neurological development of preterm infants at the corrected age of 6-54 months, and the level of neurological development was compared.Results:(1) General conditions: the gestational age at delivery in the non-medication group [36.1 weeks (35.6, 36.6 weeks)] was later than that in the medication after 34 weeks group [36.1 weeks (35.2, 36.4 weeks)] and medication before 34 weeks group [35.2 weeks (34.2, 36.2 weeks)] groups, and the differences were statistically significant (all P<0.05). After correcting for gestational age, there was no significant difference in birth weight among the three groups ( H=3.808, P=0.149). There were no significant differences in gender and the proportion of small for gestational age among the three groups (all P>0.05). (2) Short-term outcome: the incidence of wet lung was 7.0% (13/186), 11.0% (27/246) and 16.2% (32/198) in the non-medication group, medication after 34 weeks group and medication before 34 weeks group, respectively, and the difference was statistically significant ( P=0.018). There were no significant differences in the incidence rates of NRDS, hypoglycemia, sepsis, IVH, BPD, and NEC among the three groups (all P>0.05). Logistic regression analysis with gestational age and newborn birth weight as confounding factors showed that early gestational age ( OR=0.884, 95% CI: 0.837-0.933, P<0.001) and increased incidence of selective intrauterine growth restriction type I ( OR=2.967, 95% CI: 1.153-7.639, P=0.024) could both lead to an increased incidence of wet lung. (3) Long-term outcomes: a total of 109 pregnant women completed the follow-up, and 218 preterm infants with a corrected age of 6-54 months at the end of follow-up were enrolled, including 86 cases in the non-medication group, 66 cases in the medication after 34 weeks group, and 66 cases in the medication before 34 weeks group. There were no significant differences in the scores of communication, gross motor, fine motor, problem solving and personal-social among the three groups (all P>0.05). Conclusion:Prenatal administration of a single course of dexamethasone does not affect the neonatal birth weight and short-term outcomes of twin late preterm infants, and has no adverse effect on the neurological development of twin late preterm infants with a corrected age of 6-54 months.

Objective:To evaluate the outcome of laser coagulation under fetoscope for placental chorioangioma (CA).Methods:The clinical data of three pregnant women with giant CA treated by laser coagulation under fetoscope in Peking University Third Hospital from January 2018 to December 2020 were analyzed retrospectively. Relevant articles up to September 2022 were retrieved from Wanfang Database, China National Knowledge Infrastructure and PubMed, and the clinical data of all patients were retrospectively summarized. Indications and intervention effects of fetoscopic laser therapy were analyzed. Descriptive statistics was used to describe the data.Results:Thirteen patients were involved in this study including 10 cases retrieved from the databases. The average age of the pregnant women was (30.3±6.2) years old. There were 12 cases of single pregnancy and one case of twin pregnancy (monochorionic diamnionic twin pregnancy). Except for cases for which data were not available in the literatures, at the diagnosis of CA, the average gestational age was (19.9±4.5) weeks ( n=7) and the average maximum diameter of the mass was (6.1±4.1) cm ( n=6). The patients underwent fetoscopic laser therapy at an average gestational age of (25.0±2.0) weeks ( n=13) with the average maximum tumor diameter of (7.6±2.8) cm ( n=9). After treatment, the amniotic fluid volume of three cases decreased to normal. In one case, the amniotic fluid volume decreased but was still above the upper limit of the normal range. Moreover, the maximum tumor diameter decreased in four cases; the peak systolic velocity of the fetal middle cerebral artery decreased to normal in one case; fetal heart function became normal in two cases and fetal edema was relieved in one case. Among the three patients treated in our hospital, the blood supply of CA disappeared after treatment. Intrauterine fetal death occurred in two cases. The other 11 patients gave birth to live babies at the gestational age of (36.6±3.8) weeks with five through cesarean section (5/11), five through vaginal delivery (4/11) and two not reported. The birth weight of the neonates was (2 712±1 023) g and all of them survived. The gender of five neonates were reported and all were females, two of them were monochorionic diamnionic twins. No abnormality was found in the three neonates delivered in our hospital during a six-month follow-up. No abnormality was reported in the other neonates during ten days to six months of follow-up. Conclusions:Fetoscopic laser coagulation may help reduce the size of CA, decrease complications and improve pregnancy outcomes.

Objective:To analyze the clinical value of noninvasive prenatal testing (NIPT) in vanishing twin (VT) pregnancies.Methods:A total of 164 VT pregnancies that underwent NIPT in Peking University Third Hospital from January 2017 to December 2020 were enrolled. Gestational age at onset of vanishing, results of NIPT and invasive prenatal diagnosis, blood sampling time points, and pregnancy outcomes were retrospectively analyzed using two independent samples t test and Chi-square test. Results:(1) Of the 164 cases, six had positive results for NIPT, but negative results for karyotype analysis or single nucleotide polymorphism genotyping, with a false positive rate of 3.7% (6/164) for NIPT and all of them were delivered at term. Four pregnancies terminated in the second trimester, including two fetal malformation cases and one unexplained intrauterine death whose single nucleotide polymorphisms results are all normal and one inevitable abortion case due to premature rupture of membrane who refused amniocentesis. The other 154 women all gave birth to normal phenotype babies including 12 preterm ones. (2) The false-positive rate of NIPT was lower in VT pregnancies diagnosed at less than eight gestational weeks than those diagnosed after [1.5% (2/134) vs 13.3% (4/30), χ2=6.68, P=0.010]. The false-positive rate was 6.9% (4/58) in women diagnosed at or below eight weeks between the occurrence of VT and blood sampling and was 1.9% (2/106) in those with interval more than eight weeks, but without significant difference ( χ2=1.44, P=0.231). Conclusions:Although VT pregnancies exist false-positive results in NIPT, screening is still recommended based on fully informed consent to reduce unnecessary invasive prenatal diagnosis. The earlier the onset of VT, the lower the NIPT false positive rate, but whether extending the sampling interval would reduce the risk of false-positive needs further study.

Objective:To investigate the short- and long-term outcomes of fetuses with selective fetal growth restriction (sFGR).Methods:A retrospective study was conducted on monochorionic diamniotic (MCDA) twins with sFGR admitted to the Neonatal Intensive Care Unit of Peking University Third Hospital from September 2017 to December 2019. MCDA neonates delivered during the same period without significant complications were selected as the control group. MCDA twins with sFGR were divided into type Ⅰ, Ⅱ, and Ⅲ groups and then further divided into the larger and the smaller fetus subgroups according to the birth weight. These children were followed up by telephone at 2-3 years old. Height-for-age and weight-for-age Z-scores were calculated. Ages and Stages Questionnaire-Third Edition (ASQ-3) was used to determine comprehensive development. Independent sample t-test, one-way analysis of variance, non-parameter test, and Chi-square test (or rank-sum test) were used for statistical analysis. Results:(1) A total of 116 pregnant women with sFGR (232 neonates) were enrolled in this study. There were 43, 40, and 33 mothers and 86, 80, and 66 newborns in type Ⅰ, Ⅱ, and Ⅲ groups, respectively. The control group included 31 pregnant women and 62 neonates. The gestational age at onset of sFGR was younger in the type Ⅱ and Ⅲ groups than in type Ⅰ group [(23.8±4.8) and (24.1±3.1) vs (27.0±6.1) weeks, F=5.19, P<0.05; all P<0.017 during pairwise comparisons]. (2) The incidence of sepsis and treatment abandonment/death in neonates in type Ⅱ and Ⅲ groups were higher than those in type Ⅰ and control groups [neonatal sepsis: 11.3% (9/80) and 6.1% (4/66) vs 2.3% (2/86) and 0.0% (0/62), χ2=6.30, P=0.001; death or treatment abandonment rate:13.8% (11/80) and 10.6% (7/66) vs 3.5% (3/86) and 0.0% (0/62), χ2=4.68, P=0.003; all P<0.017 during pairwise comparisons]. In cases with type Ⅱ or type Ⅲ sFGR, the risk of digestive system diseases was significantly higher in the smaller fetus group than in the larger fetus group [type Ⅱ: 46.2% (37/80) vs 38.7% (31/80), χ2=16.72; type Ⅲ: 47.0% (31/66) vs 34.8% (23/66), χ2=39.69; both P<0.001], while the rate of respiratory system diseases was lower in the smaller fetus group [type Ⅱ: 35.0% (28/80) vs 45.0% (36/80), χ2=36.85; type Ⅲ: 37.9% (25/66) vs 45.4% (30/66), χ2=12.55; both P<0.001]. The incidence of neonatal sepsis in smaller fetuses was higher than that in larger ones in type Ⅱ sFGR [7.5% (6/80) vs 3.7% (3/80), χ2=4.68, P=0.034]. The incidence of neurological complications in larger fetuses was higher than that in smaller ones in type Ⅲ sFGR [15.1% (10/66) vs 4.5% (3/66), χ2=5.72, P<0.001]. (3) In type Ⅱ group, seven neonates died (one case of cerebral hemorrhage, two cases of gastrointestinal perforation, two cases of septic shock, and two cases of necrotizing enterocolitis), and four cases withdrew the treatment. In type Ⅲ group, four neonates died (two cases of necrotizing enterocolitis, one case of gastrointestinal perforation, and one case of cerebral hemorrhage), and three cases withdrew from the treatment. (4) Totally, 71 children in type Ⅰ, 61 in type Ⅱ, and 58 in type Ⅲ group were followed up at the age of 2-3. Children with type Ⅱ or type Ⅲ sFGR lagged behind those in type Ⅰ group and control group in physical growth [ M ( P25- P75), Z-scores:－0.46 (－0.87-0.42),－0.35 (－0.62-0.71), 0.05 (－0.61-0.51), and 0.14 (－0.57-0.75); H=6.20, P=0.001]. In type Ⅱ and Ⅲ groups, the smaller fetuses lagged the larger fetuses in physical growth at 2-3 years of age. ASQ-3 scores in communication, gross motor, fine motor, problem-solving and personal-social areas were all lower in type Ⅱ and Ⅲ groups than in type Ⅰ and control groups. ASQ-3 scores in the five dimensions of the smaller fetuses in the type Ⅱ group were lower than those of the larger fetuses. In the type Ⅲ group, the smaller fetuses had lower ASQ-3 scores in communication and gross motor than the larger ones [communication ability: (42.6±18.8) vs (56.4±9.4) scores, t=19.63, P<0.001; gross motor: (45.5±19.7) vs (54.5±9.7) scores, t=12.64, P=0.003]. Conclusion:The neonatal morbidity is significantly increased in type Ⅱ and Ⅲ sFGR, and babies lagged others in height, weight, and ASQ-3 score at 2-3, which is worthy of early attention.

Objective:To analyze fetoscopic cord laser therapy for management of monochorionic monoamniotic (MCMA) twin pregnancies.Methods:The clinical data of fetoscopic cord laser therapy, including cord occlusion, transection, and disentanglement in three pairs of MCMA twins from January 2020 to January 2021 in Peking University Third Hospital were summarized. Literature on cord occlusion and/or transection in MCMA twins were retrieved from Cochrane Library, PubMed, EMBASE, CBM, WanFang, and CNKI from the time at establishment to December 2020. The clinical conditions, surgical indications and methods, disease progression, and maternal and infant prognosis were analyzed.Results:Three cases of MCMA twins in this study period received fetoscopic cord laser therapy between 17-24 weeks, among which two cases gave birth at full-term without any maternal or infant complications, and one was terminated due to fetal malformation. Seven English articles including 29 MCMA twin pregnancies were retrieved. In addition to the three cases reported in this article, a total of 32 cases were analyzed. The indication of cord occlusion and/or transection included twin-reversed arterial perfusion sequence (21.9%, 7/32), fetal malformation (46.9%, 15/32), selective fetal growth restriction (sFGR) (21.9%, 7/32), twin-to-twin transfusion syndrome (TTTS) (3.1%, 1/32), TTTS combined with sFGR (3.1%, 1/32), single intrauterine death (3.1%, 1/32). Gestational age at surgery was between 14 +1 to 27 +3 weeks. No maternal complication due to the operation was reported. After exclusion of two cases who did not receive cord transection and one case was terminated due to fetal malformation, all the other 29 co-twins were born alive at the gestational age between 24 +3 to 40 weeks and birth weight between 800-3 800 g. Among the 29 live born babies, four died soon after birth with unclarified reasons in the literature and one was born with multiple malformations which were detected prenatally, and the other 24 neonates were healthy during the follow-up from 1 month to 9 years old. Conclusions:For MCMA twin pregnant women with umbilical cord entanglement or other indications for fetal reduction, cord occlusion, transection, and disentanglement using fetoscopic cord laser is safe and effective for protecting the surviving fetus.

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 understand the sleep quality and mental health status of nurses in public health emergencies, and analyze the correlation between them.Methods:A total of 128 first-line nursing staff participating in public health emergencies on February 22-23, 2020 in Tianjin Beichen Hospital, Tianjin First Central Hospital, Tianjin Fourth Central Hospital were investigated by the general data questionnaire, Pittsburgh Sleep Quality Index (PSQI), and Symptom Checklist 90 (SCL-90).Results:70.3%(90/128) of nursing staff had poor sleep quality, and the total score of PSQI was (9.71±4.01) points, which was statistically significant compared with the domestic norm ( t value was 16.479, P<0.01). The total score of SCL-90 was 1.59±0.52, which was statistically significant compared with the domestic norm ratio ( t value was 4.505, P<0.01). One-way ANOVA showed that the nursing staff's age had a significant impact on sleep quality, and the difference was statistically significant ( F value was 4.092, P<0.05). Pearson correlation analysis showed that the Pittsburgh sleep quality scale index scores and symptom self-assessment scale and somatization, force, sensitive interpersonal relationship, depression, anxiety, hostile, terrorist, paranoia, and psychosis were positively correlated( r values were 0.292-0.444, P< 0.01). Conclusions:The sleep quality and mental health status of nurses in public health emergencies are poor, and the sleep quality is correlated with mental health status.

Objective:To summarize the pregnancy outcome of monochorionic triamniotic (MCTA) triplet pregnancy and its relationship with multifetal pregnancy reduction.Methods:This study retrospectively recruited 23 women with MCTA pregnancy who delivered at Peking University Third Hospital from January 1, 2012, to January 1, 2020. All 23 cases received regular prenatal examination at our hospital from the first trimester, who were divided into two groups: selective fetal reduction group (randomly reduced one fetus, n=8) and expectant group ( n=15). Pregnancy outcome was described in all participants, differences in maternal age, gestational weeks and outcomes were compared between the two groups. The selective fetal reduction group was further divided into two subgroups: first-trimester vacuum aspiration group ( n=3) and second-trimester radiofrequency ablation group ( n=5), to evaluate the differences in pregnancy outcomes. Two independent samples- t test and Fisher's exact test were used as statistical methods. Results:(1) There was no significant difference in the gestational weeks at the end of the pregnancy [(31.7±4.1) vs (28.8±8.8) weeks], preterm delivery after 32 weeks (9/15 vs 4/8), at least two surviving children (12/15 vs 4/8) and at least one surviving child (13/15 vs 5/8) between the expectant group and the selective fetal reduction group (all P>0.05). One case with twin-twin transfusion syndrome in the expectant group underwent fetoscopic surgery at 19 weeks of gestation and delivered three live infants through cesarean section at 33 +2 weeks due to premature rupture of membranes. One case with twin reversed arterial perfusion sequence at 17 weeks of gestation refused fetal reduction and gave birth to a child at 33 weeks when one fetus's heart stopped beating and one was acardia. (2) The first-trimester vacuum aspiration group and the second-trimester radiofrequency ablation group showed no significant differences in the average gestational weeks at the end of the pregnancy [(28.5±7.6) vs (28.9±10.4) weeks, t=1.145, P>0.05], or the rate of at least one (2/3 vs 3/5, Fisher's exact test, P>0.05) or two surviving children (2/3 vs 2/5, Fisher's exact test, P>0.05). No postoperative infection or amniotic fluid leakage was reported in the subgroups. Conclusions:The pregnancy outcome of MCTA triplet with fetal reduction is not different with expectant group.

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.