INTRODUCTION: Although the combination of transcutaneous sacral nerve stimulation (tSNS) and pelvic floor exercises (PFEs) has shown significant effectiveness in treating fecal incontinence (FI) after surgery for congenital anorectal malformation (CARM), not all patients achieve satisfactory continence. Therefore, identifying which individuals will benefit from this method is crucial. METHODS: A prospective cohort study enrolled 92 children with FI. All patients underwent tSNS with PFE treatment, and an improved outcome was defined as a Wexner score ≤4. A predictive model to identify the effects of tSNS with PFEs in FI was developed based on the analysis of magnetic resonance imaging and high-resolution anorectal manometry with area under the receiver-operating characteristic curve to evaluate the predictive value of external anal sphincter (EAS) thickness index and anal squeezing pressure (ASP). RESULTS: tSNS with PFEs improved outcomes in 72 patients and led to poor outcomes in 20 (4 had their rectums deviate from the puborectalis muscle center or puborectal muscle ruptures while 16 lacked EAS with a lower ASP). The areas under the receiver-operating characteristic curve for EAS thickness index and ASP in predicting the effects of tSNS with PFEs were 0.915 (95% confidence interval 0.846–0.983, P = 0.000) and 0.886 (95% confidence interval 0.819–0.952, P = 0.000), respectively. By applying cutoff values of 0.076 for EAS thickness index and 21.95 mm Hg for ASP, tSNS with PFEs was found to be ineffective. DISCUSSION: tSNS with PFEs is effective for most patients with FI after CARM surgery, except when the rectum deviates from the puborectal muscle center, puborectal muscle rupture occurs, or EAS is absent with a low ASP.

Adolescents with 46,XY disorders of sex development (DSD) face additional medical and psychological challenges. To optimize management and minimize hazards, correct and early clinical and molecular diagnosis is necessary. We report a 13-year-old Chinese adolescent with absent Müllerian derivatives and suspected testis in the inguinal area. History, examinations, and assistant examinations were available for clinical diagnosis of 46,XY DSD. The subsequent targeting specific disease‐causing genes, comprising 360 endocrine disease-causing genes, was employed for molecular diagnosis. A novel variation in nuclear receptor subfamily 5 group A member 1 (NR5A1) [c.64G > T (p.G22C)] was identified in the patient. In vitro functional analyses of the novel variant suggested no impairment to NR5A1 mRNA or protein expression relative to wild-type, and immunofluorescence confirmed similar localization of NR5A1 mutant to the cell nucleus. However, we observed decreased DNA-binding affinity by the NR5A1 variant, while dual-luciferase reporter assays showed that the mutant effectively downregulated the transactivation capacity of anti-Müllerian hormone. We described a novel NR5A1 variant and demonstrated its adverse effects on the functional integrity of the NR5A1 protein resulting in serious impairment of its modulation of gonadal development. This study adds one novel NR5A1 variant to the pool of pathogenic variants and enriches the adolescents of information available about the mutation spectrum of this gene in Chinese population.

Objective:To conduct an in vitro study of a novel nonsense mutation in RET gene (c.2599G>T) in a Hirschsprung disease (HSCR) family to determine whether or not this mutation is pathogenic.Methods:An adenovirus overexpressing RET c. 2599G>T mutant was constructed by site-specific mutagenesis and transfected into human embryonic kidney HEK-293 cells.The cells were assigned into four groups of control (uninfected), NC (infected with a negative control adenovirus), WT (infected with an adenovirus overexpressing wild-type RET); c.2599G>T [infected with an adenovirus overexpressing mutant (c.2599g>T) RET]. Real-time polymerase chain reaction, Western blot, immunofluorescent localization, Transwell migration assay, cell counting kit-8 (CCK-8) proliferation assay and flow cytometry were utilized for exploring the functions of mutated RET gene.RET phosphorylation and activation via extracellular regulated protein kinase (ERK) were assessed by Western blot.Tukey's t-test was used to compare the mean between multiple study groups, and Dunnett- T test was used to compare the mean between multiple study groups and the control group. Results:In group c. 2599g>T cells, full-length RET protein were not detected.Transwell assay indicated that migratory capacity was lower for group c. 2599g>T cells than that for group WT cells (100.80±14.72 vs 155.20±7.89; P<0.001). CCK-8 assay revealed significantly lower ( P<0.05) proliferation for group c. 2599g>T cells than for group WT cells (0.68±0.06 vs 0.83±0.10 at 24 h, 0.90±0.10 vs 1.17±0.13 at 48 h, 1.07±0.11 vs 1.41±0.19 at 72 h, and 1.38±0.12 vs 1.68±0.15 at 96 h). Flow cytometry indicated acclerated apoptotic cell in group c. 2599g>T (3.12%) as compared with group WT (0.85%; P<0.001). After glial-derived neurotrophic factor (GDNF) treatment, the levels of P-RET and P-ERK1/2 proteins declined markedly in group c. 2599g>T (0.79±0.02, 5.60±0.02) as compared with those in group WT (72.04±0.58, 10.72±0.02)( P<0.001). Conclusions:The nonsense mutation in RET gene, c.2599G>T, is a novel functional mutation with pathogenicity.This finding has guiding significance for genetic counseling of HSCR patients.

Background:Congenital perineal hamartomas are rare, and reports of prenatal ultrasound diagnosis are limited. Perineal hamartomas are usually associated with other structural malformations, which complicate the therapeutic regime.Case presentation:We report a case of perineal hamartomas associated with rectal duplication in a female fetus. A review of the literature on similar cases was also presented. A fetus was first diagnosed with a perineal mass at 33 weeks of gestation using ultrasound examination in our hospital. Two-dimensional ultrasonography showed a hyperechoic mass resembling a scrotum in the perineum of the fetus. The pedicle connected the mass to the fetal anus. The masses were excised after birth, and perineal hamartomas were confirmed by pathological diagnosis. Rectal duplication, an associated malformation, was found during the surgery. The rectal duplication cyst was removed at the same time.Conclusion:Congenital perineal masses are rare and are usually associated with urogenital and anorectal malformations. Prenatal ultrasound should be used to assess the position and relationship between the mass and perineal organs, and to exclude other combined deformities.

BACKGROUND AND AIMS:Therapeutic blockade of the programmed cell death protein-1 (PD-1) immune checkpoint pathways has resulted in significant reactivation of T cell-mediated antitumor immunity and is a promising clinical anticancer treatment modality in several tumor types, but the durable response rate remains relatively low (15%-20%) in most patients with HCC for unknown reasons. Evidence reveals that the interferon signaling pathway plays a critical role in modulating the efficacy and sensitivity of anti-PD-1 therapy against multiple tumor types, but the mechanisms are unclear. APPROACH AND RESULTS:Using Kaplan-Meier survival analysis based on HCC databases, we found that deceased expression of interferon regulatory factor (IRF) 8 in HCC, among all the nine IRF members that regulate interferon signals, was associated with poor prognosis of patients with HCC. Moreover, gene set enrichment analysis identified the interferon-gamma and PD-1 signaling signatures as the top suppressed pathways in patients with IRF8-low HCC. Contrarily, overexpression of IRF8 in HCC cells significantly enhanced antitumor effects in immune-competent mice, modulating infiltration of tumor-associated macrophages (TAMs) and T cell exhaustion in tumor microenvironment. We further demonstrated that IRF8 regulated recruitment of TAMs by inhibiting the expression of chemokine (C-C motif) ligand 20 (CCL20). Mechanically, IRF8-mediated repression of c-fos transcription resulted in decreased expression of CCL20, rather than directly bound to CCL20 promoter region. Importantly, adeno-associated virus 8-mediated hepatic IRF8 rescue significantly suppressed HCC progression and enhanced the response to anti-PD-1 therapy. CONCLUSIONS:This work identified IRF8 as an important prognostic biomarker in patients with HCC that predicted the response and sensitivity to anti-PD-1 therapy and uncovered it as a therapeutic target for enhancing the efficacy of immune therapy.

Objectives To identify factors associated with outcomes of Kasai portoenterostomy (KPE), and predictors of 2- and 5- year native liver survival (NLS) for infants achieved jaundice clearance (JC) within 6 months of KPE.Methods This retrospective cohort study was conducted on 151 patients with type III biliary atresia (BA) who underwent KPE at our center. Univariate analysis and logistic regression analyses were performed to identify factors associated with NLS in infants achieved JC. Kaplan–Meier curves and log-rank tests were used to estimate the NLS, and the Cox proportional hazards regression model identified variables most associated with 2- and 5-year NLS at 6 months post-KPE. A receiver operating characteristic (ROC) curve was used to evaluate the predictive value of these factors.Results The 2- and 5-year NLS of infants achieved JC at 3 months post-KPE were not different from those achieved JC earlier. Operation age and total bile acid (TBA) were factors associated with JC. For infants who have achieved JC, DB was the only factor associated with 2-year NLS, the AUC was 0.872, the cutoff value was 14 μmol/L; ALB and DB were factors associated with 5-year NLS, the AUCs were 0.894 and 0.95, and the cutoff values were 39 g/L and 14 μmol/L, respectively.Conclusions NLS should be estimated at 6 months post-KPE. Preoperative factors are not predictive of NLS. For infants cleared jaundice, DB and ALB can predict NLS with good performance.What’s Known on This Subject Age, liver stiffness, and CMV infections are factors associated with outcomes of Kasai portoenterostomy. Jaundice clearance is directly associated with native liver survival; however, even with successful surgery, liver pathology in most cases will progress to end-stage cirrhosis.What This Study Adds No preoperative factors are predictive of native liver survival (NLS). Infants cleared jaundice after 3 months of KPE can achieve the same NLS as those cleared jaundice earlier. For infants cleared jaundice, 6-month postoperative DB and Albumin are predictive of NLS.How this study might affect research, practice or policy In this study, we argued that 6 months post-KPE was the appropriate timing for predicting NLS; direct bilirubin (DB) and albumin (ALB) at 6 months post-KPE can be used to predict 2- and 5-year NLS with good performance.Article Summary Retrospective analysis revealed it’s difficult to predict outcomes of Kasai portoenterostomy (KPE) preoperatively; jaundice clearance should be evaluated at 6 months after KPE, for infants cleared jaundice, 6-month postoperative DB and Albumin are predictive of NLS.### Competing Interest StatementThe authors have declared no competing interest.### Funding StatementNational Natural Science Foundation of China, 82170529; the National Key Researech and Development Program, 2021YFC2701003; Liaoning Revitalization Talents Program, XLYC1908008.### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Ethical approval for this study was obtained from the Research Ethics Committee of Shingjing Hospital, China Medical UniversityI confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll data produced in the present study are available upon reasonable request to the authors All data produced in the present work are contained in the manuscript* KPE : Kasai portoenterostomy BA : biliary atresia JC : jaundice clearance JUC : jaundice unclearance LT : liver transplantation NLS : native liver survival PLT : platelet INR : international normalized ratio ALT : alanine aminotransferase AST : aspartate aminotransferase GGT : gamma-glutamyl transpeptidase TBA : total bile acid ALB : albumin TB : total bilirubin DB : direct bilirubin IB : indirect bilirubin APRI : AST/PLT CMV : cytomegalovirus ROC : receiver operating characteristic curve AUC : area under the ROC

We present a rare case of neonatal duodenal malformation. Herein, we provide a differential diagnosis for a large abdominal cyst in a prenatal fetus and explore the possible causes and treatment of neonatal megaduodenum. We retrospectively analyzed one case of megaduodenum from fetal examination to neonatal diagnosis and treatment. Ultrasonography of the fetus at 12 weeks' gestation revealed a cystic mass in the abdominal cavity, measuring about 0.7 cm × 0.5 cm × 0.4 cm. The cystic mass grew in equal proportion to the fetus. At 32 weeks’ gestation, the peritoneal cystic mass was enlarged to 9.0 cm × 7.9 cm × 5.8 cm, and the mass was found to be communicating with the stomach. Intraoperatively, the mass was about 10-cm long and 6 cm in diameter. The duodenal papilla was located about 1.5 cm above the proximal junction. The megaduodenum was removed, and the distal and proximal intestines were anastomosed end-to-end. The patient recovered smoothly postoperatively and gained 550 g 1 month after discharge. The results of amniotic fluid high-throughput sequencing identified Seq [Grch37] del (16) (p12.2) Chr16: g.22000000_22440000del. There was a copy number deletion of about 0.44 Mb on the short arm of chromosome 16, which was suspected to be pathogenic and involved seven protein-coding genes. Histopathologically, in the same paraffin specimen, there was a mixture of stunted ganglion cells, ganglion dysplasia, and well-developed ganglion cells. Neonatal megaduodenum was considered as a differential diagnosis of the large cystic mass in the fetal abdomen. Further additional evidence was needed to prove whether the mutation was pathogenic, which also suggested that the etiology is related to genetic variation. The nerve plexus and ganglion cells were poorly developed, which further supported that the intestinal nerve abnormality was the etiology. Excision was safe and effective for treating megaduodenum.

Objective:To compare the safety and efficacy of intrapartum operation with those of non-intrapartum operation in neonates with congenital abdominal wall defects.Methods:From January 2009 to December 2021, clinical data were retrospectively for 70 neonates with congenital abdominal wall defects.There were gastroschisis ( n=12) and omphalocele ( n=58). Intrapartum ( n=34) and non-intrapartum ( n=36) operations were performed.Staging operation, mesh application, blood transfusion, exogenous blood transfusion, ventilator use, incision infection, hypoglycemia, liver damage, central vein-related infection, antibiotic use, intravenous nutrition time, feeding time, length of hospital stay, recovery and postoperative follow-ups were compared between two groups. Results:There were zero and eight cases of exogenous transfusion in intrapartum and non-intrapartum operation groups ( P<0.05). Umbilical cord blood transfusion was performed in intrapartum operation group ( n=4, P=0.25). And there were three and one case of staging operation in intrapartum and non-intrapartum operation groups ( P=0.28). Patch repair was performed ( n=1 each, P=1.00). Postoperative incision infection occurred in one and four cases in intrapartum and non-intrapartum operation groups ( P=0.18) and the difference was not statistically significant.There were zero and two cases with central vein-related infection in intrapartum and non-intrapartum operation groups ( P=0.49) and the difference was not statistically significant.No significant inter-group differences existed in ventilator support, TPN time, milk opening time, antibiotic use or hospital stay.Intrapartum operation group had a curative rate of 97.06% (one neonate withdrawing from the hospital) and non-intrapartum operation group had a curative rate of 97.22% (one neonate death due to respiratory failure); the difference was not statistically significant.Follow-up results showed that height and weight in two groups were within two standard deviations of each other for children of the same age.The development of nervous system was normal and there was no case of reoperation for intestinal obstruction. Conclusion:Intrapartum and non-intrapartum operations are equally safe and effective for treating congenital abdominal wall defects.Neonates undergoing intrapartum operation do not need exogenous blood transfusion to avoid risks associated with allogeneic blood transfusion.

Objective:To explore the safety and efficacy of laparoscopic transcystic common bile duct exploration (LTCBDE) for severe choledochal obstruction in infants aged under 3 months.Methods:Clinical data, surgical approaches and postoperative care were reviewed for two young boys aged under 3 months with cholelithiasis plus severe common bile duct obstruction from December 2018 to March 2020. There were jaundice, bile-free stool and abnormal liver function. Ultrasound and magnetic resonance cholangiopancreatography (MRCP) indicated choledocholithiasis with terminal obstruction of common bile duct and bile duct dilatation. Conservative treatment failed. Operative age was 67 and 86 days and operative weight 3. 33 and 4. 65 kg respectively. LTCBDE was performed under general anesthesia. Postoperative biliary tract irrigation was performed by indwelling drainage tube and oral ursodeoxycholic, liver function, ultrasonography and cholangiography examined.Results:Both cases were successfully operated. Choledocholithiasis was cleared without a conversion into open surgery. Without intraoperative complications, postoperative regression was satisfactory. Direct bilirubin normalized and drainage tube slipped off at Week 2 post-operation. Another case reverted to normal direct bilirubin at Week 8 post-operation and biliary drainage tube was removed at Week 10 post-operation. During follow-ups, there was no recurrent choledocholithiasis, dilatation of common bile duct or obstruction at distal common bile duct.Conclusion:For cholelithiasis in very young infants with complete obstruction of common bile duct, individualized treatment should be adopted according to specific patient situation. LTCBD is both safe and feasible for infants aged under 3 months.

Enzalutamide (ENZ) is a second-generation androgen receptor (AR) antagonist used for the treatment of castration-resistant prostate cancer (CRPC) and reportedly prolongs survival time within a year of starting therapy. However, CRPC patients can develop ENZ resistance (ENZR), mainly driven by abnormal reactivation of AR signaling, involving increased expression of the full-length AR (ARfl) or dominantly active androgen receptor splice variant 7 (ARv7) and ARfl/ARv7 heterodimers. There is currently no efficient treatment for ENZR in CRPC. Herein, a small molecule LLU-206 was rationally designed based on the ENZ structure and exhibited potent inhibition of both ARfl and constitutively active ARv7 to inhibit PCa proliferation and suppress ENZR in CRPC. Mechanically, LLU-206 promoted ARfl/ARv7 protein degradation and decreased ARfl/ARv7 heterodimers through mouse double minute 2-mediated ubiquitination. Finally, LLU-206 exhibited favorable pharmacokinetic properties with poor permeability across the blood-brain barrier, leading to a lower prevalence of adverse effects, including seizure and neurotoxicity, than ENZ-based therapies. In a nutshell, our findings demonstrated that LLU-206 could effectively inhibit ARfl/ARv7-driven CRPC by dual-targeting of ARfl/ARv7 heterodimers and protein degradation, providing new insights for the design of new-generation AR inhibitors to overcome ARfl/ARv7-driven CRPC.

目的 总结分析婴儿期行先天性巨结肠根治手术患者术后非计划再入院的原因.方法 回顾性分析中国医科大学附属盛京医院新生儿外科2011年10月至2020年9月接受手术治疗的1至6月龄先天性巨结肠患者的临床资料,包括病理分型 、手术方式 、再入院原因 、再入院时间等.结果 资料完整的先天性巨结肠患者共326例,男271例(83.1％),女55例(16.9％),手术时平均月龄(2.53±1.32)个月.其中51例出院后非计划再次入院,再入院率15.64％,再入院总次数为64次,其中10例多次入院.出院后再入院时间分布情况:1个月内再入院28例(54.9％);1个月至1年再入院12例(23.5％),1至3年再入院11例(21.57％).再入院主要原因分布情况:巨结肠术后小肠炎56例次(87.5％)、肠梗阻6例次(9.4％),电解质紊乱2例次(3.1％).其中2例(0.6％)行手术治疗,1例术后3个月因肠梗阻行肠粘连松解术,1例术后3年因巨结肠复发行腹腔镜下结肠次全切除及结肠翻转术.按入院时间划分,2017年及之前手术248例保留肌鞘较长,再入院45例(18.1％);2018年至2020年78例保留短肌鞘,再入院6例(7.7％);差异具有统计学意义(χ2=4.913,P=0.027).结论 小肠结肠炎和肠梗阻是导致巨结肠手术后再次入院的主要原因,再次入院时间大多在术后1个月内.术后增加随访频率可能会减少术后早期再入院的发生.此外,术中保留肌鞘较短可减少术后小肠结肠炎和肠梗阻的发生,降低再入院率.

目的:探讨思连康联合蒙脱石散治疗小儿急性肠炎的临床疗效和对血清IgG、IgA、IgM水平的影响.方法:选择我院2016年8至2017年8月收治的86例小儿急性肠炎患儿,根据随机数字表法将其随机分为观察组及对照组,两组患儿均给予常规治疗,对照组患儿在常规治疗基础上给予蒙脱石散治疗,观察组在对照组基础上给予思连康治疗.观察和比较两组患儿治疗后的疗效、呕吐缓解时间、发热消退时间、大便恢复正常时间、腹痛缓解时间、粪便常规恢复正常的时间及两组治疗前后的血清IgG、IgA、IgM水平的变化情况.结果:治疗后,观察组和对照组的总有效率分别为95.2％(40/42)、79.5％(35/44),观察组总有效率显著明显高于对照组(P＜0.05);观察组患儿的呕吐缓解时间、发热消退时间、大便恢复正常时间、腹痛缓解时间及粪便常规恢复正常的时间均明显短于对照组(P＜0.05).治疗后,两组患儿的血清IgG、IgA、IgM水平均较治疗前明显升高,且观察组治疗后血清IgG、IgA、IgM水平均明显高于对照组(P＜0.05).结论:与单用蒙脱石散治疗相比,思连康联合蒙脱石散治疗小儿急性肠炎可有效提高治疗效果,缩短患儿临床症状改善时间,提高患儿免疫力.

Objective To summarize the technical experience of extracorporeal membrane oxygena-tion(ECMO)catheterization in children. Methods Data of patients that received ECMO treatment in the pe-diatric intensive care unit between October 2016 and October 2018 were analyzed retrospectively. The age, weight,diagnosis,complications and the final outcomes of the patients,as well as the working mode,catheter-ization mode and duration of ECMO were collected. Results A total of 15 children were treated with ECMO,including 5 males and 10 females. The median age(range) was 4. 9 (1. 0-11. 0)years and the median weight(range) was 21. 5(8. 5-49. 0)kg. There were 5 cases of fulminant myocarditis,7 cases of severe pneu-monia,3 cases of septic shock,8 cases of venous-arterial bypass( VA mode),and 7 cases of venous-venous bypass(VV mode). All the 15 patients underwent percutaneous catheterization. Two patients that experienced difficulty in percutaneous catheterization turned to open catheterization. None abandoned ECMO due to the difficulty in catheterization. The position and depth of the catheter,and the flow rate required no further ad-justment. The mean ECMO duration was 96. 8(1-366)h. Weaning was successful in 8 cases(53%). One case was transferred and 8 cases were dismissed,and the survival rate was 60%. There were 2 cases of bleeding at the site of catheter entrance,one treated with local compression and the other with suture. There was 1 case of femoral artery thrombosis that was relieved by percutaneous femoral artery angiography and intracavitary for-mation. Another case developed carotid artery thrombosis and had been undergoing antithrombotic therapy and following-up. One case had nerve injury in the left lower extremity that was relieved by oral vitamin Bs and low frequency electrical stimulation. Conclusion Catheterization is the basis of ECMO execution. Catheter-ization method should be individualized. Percutaneous catheterization is the choice of thumb due to its safety and simplicity. In case of failure,or during the extra-cardiac compression,the surgical method should be taken quickly,and the catheter should be placed in an open or partly-open manner. Proficient catheterization tech-nique ensures the smooth application of ECMO in children.

Objective To identify the disease-causing gene mutation in two families of Hirschsprung's disease (HSCR).Methods Two HSCR families from Liaoning Province were collected to analyze genomic DNA.Whole-exome genome mutation screening and copy number variation (CNV) analysis were performed on whole-genome DNA extracted from blood using nextgeneration sequencing (NGS) technology.Combining the hazard and pathogenicity analysis of mutation and clinical phenotype of family members screening susceptible pathogenic gene for sequencing results.Then classical Sanger' s method was applied for verifying the obtained results.Results Among 4 persons in family 1,both children were affected,the mother had similar clinical manifestations but the diagnosis was absent,the father had no phenotype.After filtering out common mutations and synonymous mutations,633 SNPs and 35 InDel mutations were detected by wholeexome sequencing.The sequencing results revealed heterozygous mutation c.2599G＞T in exon 14 encoding region of RET gene and it was confirmed as a pathogenicity mutation through the hazard and pathogenicity analysis of mutated protein.Among 4 persons in family 2,both offsprings were identified as HSCR,but one of them dying in neonatal period failed to obtain a peripheral blood sample.Sequencing results revealed 609 SNPs and 30 InDel mutations.Comprehensive analysis of mutations,genetic patterns,clinical features and other factors failed to detect a distinct pathogenic mutation in this family.Conclusions NGS can screen out new HSCR-related gene mutations and provide etiological insights of HSCR.

目的 探讨微创技术对胎儿胸腔腹腔巨大囊肿围生期的治疗。 方法 收集2015年6～12月接受产前干预并在新生儿期运用微创技术成功治疗的胎儿巨大胸腔囊性肿物和腹腔囊性肿物各1例，回顾性分析其临床症状、住院时间、囊肿大小、包块性质、影像学检查特点、处理方式，病理诊断及预后随访。 结果 1例为胎儿胸腔肿物，胎龄34周行胎儿胸腔肿物穿刺抽液术，出生后第8天行胸腔镜下纵隔巨大囊性肿物切除术，术后病理为前纵隔囊性畸胎瘤。另1例为腹腔巨大囊性肿物，于胎龄36周行胎儿期囊肿穿刺缓解胸腹腔压迫症状，出生后第5天行腹腔镜辅助下经脐巨大卵巢囊肿核除术，术后病理为卵巢囊肿。2例患儿胎儿期均出现了囊肿压迫周围脏器的表现，给予胎儿期囊肿穿刺治疗，出生后行腔镜辅助下肿物根治性切除术，术后获治愈，随访无复发。 结论 及时必要的产前胎儿囊肿穿刺减压、生后早期的微创手术治疗对于改善胎儿期巨大胸、腹腔囊性肿物的预后有良好的效果，有利于患儿顺利度过围生期，减少严重并发症的发生。

目的 总结近5年产前诊断的先天性膈疝(congenital diaphragmatic hernia，CDH)的围生期诊治经验，探讨CDH在胎儿期的多学科会诊制度，新生儿期的手术治疗时机、手术方法及临床疗效。 方法 收集我院2012年5月至2017年5月通过产前诊断的先天性膈疝患儿38例，对病例进行回顾性分析。 结果 6例患儿生后家长放弃治疗，其中2例经高频通气及一氧化氮吸入仍不能维持有效血氧饱和度，余患者均行手术治疗。胸腔镜手术31例；5例中转开胸，其中2例膈肌巨大缺损，3例患儿不能耐受气胸。获得随访29例(90.6%)，随访7个月～4年10个月，平均(29±13)个月，均无复发或严重并发症。 结论 CDH的诊治需针对每个患儿的呼吸循环稳定性、肺发育情况、合并畸形等具体情况来制定个体化精准治疗方案。胸腔镜膈肌修补手术对于新生儿先天性膈疝的治疗是安全可行的方法。

Objective To investigate the fetal management of prenatally diagnosed fetal mediastinal masses and the initial experience of neonatal thoracoscopic minimally invasive treatment. Methods We per-formed a retrospective study from November 2015 to November 2016 of all newborns affected by mediastinal masses and treated by thoracoscopic surgery. This group of cases were found with mediastinal masses by pre-natal ultrasound. The earliest detection of abnormal time was 16 to 31 weeks of pregnancy,with an average of 25 weeks. In the fetal period,the patients were treated with multidisciplinary consultation and individual man-agement. Prenatal examinations helped us except for chromosomal abnormalities and other organ abnormali-ties. After birth,the patients underwent CT and MRI examination. The diameter of the tumor was 1. 7 to 5. 7 cm,with an average of 3. 2 cm. The operative age was 4 to 29 days,with an average of 12. 4 days. This group of newborns were performed thoracoscopic mass resection and confirmed by intraoperative pathological exam-ination. Results After individualized precise prenatal management,all children were born successfully and confirmed that prenatal diagnosis was accurate. All mediastinal masses were completely excised in the neo-natal period. Five mediastinal masses were completely excised. One posterior mediastinum immature teratoma was converted to open thoracotomy. The mean operative duration was 112 min(100 to 150 min). There was no operative complication with a minimal amount of blood loss. With a smooth recovery,the hospital stay was 11-17 days. Pathological results included:1 esophageal duplication,2 bronchogenic cysts,1 lymphangioma, 1 cystic teratoma of anterior mediastinum,1 immature teratoma of posterior mediastinum. During a mean fol-low-up period of 8-14 months,neither complication nor recurrence occurred. Conclusion These are the pre-conditions for early treatment of neonatal patients with mediastinal masses,including definite prenatal diagno-sis,multidisciplinary consultation system and individualized and accurate fetal management. Throcoscopic ex-cision of mediastinal masses is both feasible and safe in neonates. Proper preoperative case selection may pre-vent a conversion into thoracotomy due to huge solid mass.

Objective To summarize the clinical experiences of 28 infants ovarian cysts treated by laparoscopic-assisted transumbilical extracorporeal cystectomy ( LATEC) in the last 4 years. Methods Twenty-eight neonatal and small infancy ovarian cysts were collected from June 2012 to June 2016. Retrospective analysis their clinical symptoms, discovery time, length of hospitalization, cyst size and nature, imaging characteristics, prenatal intervention, surgical treatment, postoperative pathological examination and follow-ups. Results The involved sides were unilateral (n=23) and bilateral (n=5). The monthly ages were <1 (n=11), 1-3 (n=11) and 3-6 (n=6). The manifestations included abdominal mass (n=27) and abdominal distension (n=1). 20 cases were found in fetal period, of which 1 case was treated by prenatal ultrasound guided cyst decompression. The average length of hospitalization was 7. 5 (4 -20) days. The sizes of ovarian cyst size were 4-5 cm (n=11), 5-10 cm (n=15) and >10 cm (n=2). All patients underwent laparoscopic-assisted transumbilical extracorporeal cystectomy ( LATEC) , including excision of ipsilateral appendectomy ( n=15) and simple cystectomy (n=13). The natures of ovarian cyst were simple (n=21), follicular (n=4) and serous (n=3). All 28 cases were cured and remained recurrence-free during follow-ups. Conclusion LATEC is both safe and effective for neonatal and infantile ovarian cysts. When abdominal cystic mass is larger than 5 cm or cysts fail to disappear and even expand further, surgery is required. When cyst size is<5 cm but its origin comes from ovary or other sites, exploratory surgery is indicated. For huge cysts in fetus, it is necessary to perform such a fetal mini-invasive procedure as puncture decompression.

Objective Dickkopf1 (Dkk1) is an extracellular negative regulator of Wnt signaling pathway.This study was intended to explore the differential expression of Dkk1 in cloaca and hindgut in normal and anorectal malformation (ARM) rat embryos and examine potential association between Dkk1 and abnormal development of cloaca and hindgut in ARM.Methods Ethylenethiourea (ETU) was administered to 24 pregnant rats at gestational Day 10 via gastric gavage.And another 16 control pregnant rats received saline alone.The gestational ages of collected specimens were 12-17,19 and 21 days respectively.Based upon anorectal morphology,the embryos were divided into two groups.Group ARM:ARM fetuses born from pregnant rats received ETU (n =96) and control group (n =96).Normal fetuses were from pregnant rats receiving saline.Cloaca and hindgut tissues were dissected microscopically for extracting total RNA and protein.Real-time polymerase chain reaction (RT-PCR) and Western blot were performed to detect the expressions of Dkk1 mRNA and protein respectively.The experiment was analyzed by two-way ANOVA of randomized block design.Results Dkk1 mRNA and protein were detected in both groups.The expression of Dkk1 peaked at Day 16 in cloaca and hindgut of control group (2.77 ± 0.06,3.20 ± 0.76) while the expression of Dkk1 fluctuated in ARM group.The expression levels of Dkk1 mRNA and protein were remarkably different during cloacal and hindgut development between norrnal (2.00 ± 0.52,1.98 ± 0.65) and ARM embryos (0.96 ± 0.14,0.87 ± 0.14,P＜0.05).Conclusions A down-regulation of Dkk1 in cloaca and hindgut development may be partially related to maldevelopment of cloaca and hindgut in ARM.