The urinary bladder is an innovation of eutherian mammals to manage liquid waste. However, bladder development and its embryonic function remain poorly understood. Here, we report that in both humans and mice the bladder emerges from the cloaca as a rostral outgrowth, which is flanked by the umbilical arteries. Arrest of the outgrowth, as seen in Shh-null mouse embryos, causes bladder agenesis and unexpected severe defects of the umbilical arteries, suggesting that the outgrowth epithelial signal Shh coordinates development of both the bladder and the umbilical arteries. The signaling molecule Wnt2 is restricted to the rostral outgrowth mesenchyme and its expression is dramatically downregulated in Shh-null mutants. Furthermore, Wnt2-null mutants develop a small bladder and single umbilical artery defects. Collectively, we uncover an unexpected co-development mechanism of the bladder and umbilical arteries orchestrated by the cloacal outgrowth signals. The co-development paradigm offers a conceptual framework to understand evolution and development of the bladder.

BACKGROUND:Despite the extensive study of MYCN-amplified neuroblastomas, there is a significant unmet clinical need in MYCN non-amplified cases. In particular, the extent of heterogeneity within the MYCN non-amplified population is unknown. METHODS:A total of 1566 samples from 16 datasets were identified in Gene Expression Omnibus (GEO) and ArrayExpress. Characterisation of the subtypes was analysed by ConsensusClusterPlus. Independent predictors for subgrouping were constructed from the single sample predictor based on the multiclassPairs package. Findings were verified using immunohistochemistry and CIBERSORTx analysis. RESULTS:We demonstrate that MYCN non-amplified neuroblastomas are heterogeneous and can be classified into 3 subgroups based on their transcriptional signatures. Within these groups, subgroup_2 has the worst prognosis and this group shows a 'MYCN' signature that is potentially induced by the overexpression of Aurora Kinase A (AURKA); whilst subgroup_3 is characterised by an 'inflamed' gene signature. The clinical implications of this subtype classification are significant, as each subtype demonstrates a unique prognosis and vulnerability to investigational therapies. A total of 420 genes were identified as independent subgroup predictors with average balanced accuracy of 0.93 and 0.84 for train and test datasets, respectively. CONCLUSION:We propose that transcriptional subtyping may enhance precision prognosis and therapy stratification for patients with MYCN non-amplified neuroblastomas.

Purpose Develop and validate a nomogram for predicting intestinal resection in pediatric intussusception suspecting intestinal necrosis.Patients & methods Children with intussusception were retrospectively enrolled after a failed air-enema reduction in the outpatient setting and divided into two groups: the intestinal resection group and the non-intestinal resection group. The enrolled cases were randomly selected for training and validation sets with a split ratio of 3:1. A nomogram for predicting the risk of intestinal resection was visualized using logistic regression analysis with calibration curve, C-index, and decision curve analysis to evaluate the model.Results A total of 547 cases were included in the final analysis, of which 414 had non-intestinal necrosis and 133 had intestinal necrosis and underwent intestinal resection. The training set consisted of 411 patients and the validation cohort included 136 patients. Through forward stepwise regression, four variables (duration of symptoms, C-reaction protein, white blood cells, ascites) were selected for inclusion in the nomogram with a concordance index 0.871 (95% confidence interval: 0.834-0.908).Conclusion We developed a nomogram for predicting intestinal resection in children with intussusception suspecting intestinal necrosis after a failed air-enema based on multivariate regression. This nomogram could be directly applied to facilitate predicting intestinal resection in pediatric intussusception suspecting necrosis.

目的 探讨小儿外科病例三维模型在临床见习教学中的应用效果.方法 使用Amira软件构建小儿外科病例三维模型,在临床见习教学中利用三维模型开展病例讨论.采用整群抽样方法,选取2021年2月～2021年5月在温州医科大学附属第二医院育英儿童医院小儿外科见习的2017级五年制儿科学专业30名学生为研究对象.按照抽签方式将30名学生随机分为试验组和对照组,每组15名学生.试验组学生在传统病例讨论教学方式的基础上,增加病例三维模型教学内容;对照组学生采用传统病例讨论教学方式.教学后,比较两组学生出科理论考试成绩和教学满意度调查结果.结果 试验组和对照组学生的出科考试成绩分别为(90.33±3.64)分和(84.60±3.68)分,两组差异具有统计学意义(P<0.001).教学满意度调查结果显示,试验组学生不满意率为6.7％(1/15)、一般满意率为26.7％(4/15)、满意率为66.7％(10/15),对照组学生不满意率为20.0％(3/15)、一般满意率为66.7％(10/15)、满意率为13.3％(2/15),两组差异具有统计学意义(P=0.012).结论 采用Amira软件构建小儿外科病例三维模型并将其应用于临床见习教学,有助于提高学生出科考试成绩和教学满意度.

Objective:This study investigated the effects of bis (2-butoxyethyl) phthalate (BBOP) on the onset of male puberty by affecting Leydig cell development in rats.Methods:Thirty 35-day-old male Sprague-Dawley rats were randomly allocated to five groups mg/kg bw per day that were gavaged for 21 days with BBOP at 0, 10, 100, 250, or 500 mg/kg bw per day. The hormone profiles; Leydig cell morphological metrics; mRNA and protein levels; oxidative stress; and AKT, mTOR, ERK1/2, and GSK3β pathways were assessed.Results:BBOP at 250 and/or 500 mg/kg bw per day decreased serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels mg/kg bw per day (P < 0.05). BBOP at 500 mg/kg bw per day decreased Leydig cell number mg/kg bw per day and downregulated Cyp11a1, Insl3, Hsd11b1, and Dhh in the testes, and Lhb and Fshb mRNAs in the pituitary gland (P < 0.05). The malondialdehyde content in the testis significantly increased, while Sod1 and Sod2 mRNAs were markedly down-regulated, by BBOP treatment at 250-500 mg/kg bw per day (P < 0.05). Furthermore, BBOP at 500 mg/kg bw per day decreased AKT1/AKT2, mTOR, and ERK1/2 phosphorylation, and GSK3β and SIRT1 levels mg/kg bw per day (P < 0.05). Finally, BBOP at 100 or 500 μmol/L induced ROS and apoptosis in Leydig cells after 24 h of treatment in vitro (P < 0.05).Conclusion:BBOP delays puberty onset by increasing oxidative stress and apoptosis in Leydig cells in rats.The graphical abstract is available on the website www.besjournal.com.

Di-n-pentyl phthalate (DPeP) is an endocrine-disrupting phthalate plasticizer. The objective of this study was to investigate the effect of DPeP on adrenocortical function in adult male rats following in utero exposure. DPeP (0, 10, 50, 100, and 500 mg/kg/day) was administered by gavage to pregnant Sprague-Dawley rats from gestational day 14 to 21. The morphology and function of the adrenal cortex in 56-day-old male offspring were studied. DPeP at 100 and 500 mg/kg/day significantly reduced serum aldosterone levels and at 500 mg/kg/day markedly reduced corticosterone and adrenocorticotropic hormone levels. DPeP at 10-500 mg/kg markedly reduced the thickness of zona glomerulosa without affecting the thickness of zona fasciculata. DPeP significantly downregulated the expression of Agtr1a, Mc2r, Scarb1, Cyp11a1, Hsd3b1, Cyp21, Cyp11b1, Cyp11b2, Nr5a1, Nr4a2, and Bcl2 genes as well as their proteins. DPeP at 500 mg/kg/day significantly increased phosphorylated AMPK, while DPeP at 100 mg/kg/day and higher doses reduced phosphorylated AKT1 and total SIRT1 level. DPeP at 100 and 500 μM markedly induced reactive oxygen species and apoptosis in H295R cells after 24 h of culture. In conclusion, in utero exposure to DPeP disrupts adrenocortical function of the adult male offspring by (1) increasing AMPK phosphorylation and decreasing AKT1 phosphorylation and SIRT1 levels, (2) reducing adrenocorticotropic hormone levels, and (3) possibly inducing oxidative stress and apoptosis.

Background This study aimed to identify survival risk factors in Chinese children with hepatoblastoma (HB) and assess the effectiveness of the new treatment protocol proposed by the Chinese Children’s Cancer Group (CCCG) in 2016. Methods A multicenter, prospective study that included 399 patients with HB from January 2015 to June 2020 was conducted. Patient demographics, treatment protocols, and other related information were collected. Cox regression models and Kaplan–Meier curve methods were used. Results The 4-year event-free survival (EFS) and overall survival (OS) were 76.9 and 93.5%, respectively. The 4-year EFS rates for the very-low-risk, low-risk, intermediate-risk, and high-risk groups were 100%, 91.6%, 81.7%, and 51.0%, respectively. The 4-year OS was 100%, 97.3%, 94.4%, and 86.8%, respectively. Cox regression analysis found that age, tumor rupture (R +), and extrahepatic tumor extension (E +) were independent prognostic factors. A total of 299 patients had complete remission, and 19 relapsed. Patients with declining alpha-fetoprotein (AFP) > 75% after the first two cycles of neoadjuvant chemotherapy had a better EFS and OS than those ≤ 75%. Conclusions The survival outcome of HB children has dramatically improved since the implementation of CCCG-HB-2016 therapy. Age ≥ 8 years, R + , and E + were independent risk factors for prognosis. Patients with a declining AFP > 75% after the first two cycles of neoadjuvant chemotherapy had better EFS and OS. Graphical abstract

Objective:To explore the characteristics, diagnosis, treatment and prognosis of eosinophilic solid and cystic renal cell carcinoma in children.Methods:Retrospective analysis was performed for clinical data of a child with eosinophilic solid and cystic renal cell carcinoma.The databases of PubMed and Web of Science were searched with the key words of "eosinophilic solid and cystic renal cell carcinoma" or "eosinophilic solid and cystic renal cell cancer" or "eosinophilic solid and cystic renal cell carcinoma" in Wanfang and CNKI.The searching cutoff was up to December 2021.Duplicate literatures were excluded and clinicopathological features and prognosis of this kind of tumor summarized.Results:This 9-year-old girl was hospitalized for "detecting a bulge of right abdomen for 3 days" . Preoperative imaging examination indicated that right kidney occupied a large space.Then radical resection of giant tumor of right kidney was performed.Pathological diagnosis was eosinophilic solid and cystic renal cell carcinoma in childhood.Immunohistochemical hint: CK20(+ ); PAX-8(+ ); CD117 (+ ); CK7(-). There were no postoperative radiochemotherapy.No recurrence or metastasis occurred during 6-month follow-ups.Six cases from the literature search and this one had a total of 6 children with eosinophilic solid and cystic renal cell carcinoma, including 4 boys and 2 girls with an average age of 14(9-17) years.Two cases had abdominal pain, abdominal mass or pain in both lower extremities and none of them showed clinical features of tuberous sclerosis complex (TSC). The involved side was bilateral ( n=1), left ( n=1), right ( n=2) and non-specified ( n=2). Partial ( n=1) and radical ( n=6) nephrectomy were performed.One child had an involvement of inferior vena cava plus pulmonary embolism and liver metastasis occurred 2 years after adjuvant chemotherapy.TSC gene mutation was detected in 5 cases, all of which were TSC2 gene mutation.There was no tumor recurrence during a median follow-up period of 18(6-132) months. Conclusion:As a rare disease in children, eosinophilic solid renal cell carcinoma and cystic renal cell carcinoma generally have non-specific clinical symptoms.Auxiliary examination has no obvious special manifestations, yet it has unique pathological features.Some cases have TSC gene mutation and the prognosis is excellent after radical operation.

目的:介绍一种构建虚拟喉镜(VL)的方法及其在先天性梨状窝瘘(CPSF)诊治中的临床应用.方法:从CPSF患儿身上获取CT数据,使用三维可视化软件对喉部解剖结构及上呼吸道进行三维重建、表面渲染及图像分割.获取计算机辅助的内外部解剖视图和交互式穿通连续的内腔视图.结果:成功构建CPSF患儿三维喉部和上呼吸道解剖结构.获取VL梨状窝的常规视图与传统喉镜视图比较情况.LV能够在逆行和顺行可视化中获得梨状窝的独特视图.分割和透明化三维解剖模型,能显示CPSF解剖结构和走向以及与周围器官的空间关系.在低年资组中,其有利于诊断的比例为85.71％,而在高年资组中,其有利于诊断的比例为57.89％(P<0.05);在低年资组和高年资组中,其有利于术中解剖参考的比例分别为89.29％和84.21％(P>0.05).结论:VL作为评估CPSF及其范围的非侵入性工具具有潜在临床应用价值.结合二维图像,可为CPSF的诊治提供超越传统内窥镜检查的信息.VL可能对低年资医师的参考价值更大.

Phthalates may interfere with the biosynthesis of steroid hormones in the adrenal cortex. Bis (2-butoxyethyl) phthalate (BBOP) is a phthalate containing oxygen atoms in the alcohol moiety. In this study, 35-day-old male Sprague-Dawley rats were daily gavaged with BBOP (0, 10, 100, 250, and 500 mg/kg body weight) for 21 days. BBOP did not affect the weight of body and adrenal glands. BBOP significantly reduced serum corticosterone levels at 250 and 500 mg/kg, and lowered aldosterone level at 500 mg/kg without affecting adrenocorticotropic hormone. BBOP did not alter the thickness of the adrenal cortex. BBOP significantly down-regulated the expression of steroidogenesis-related genes (Scarb1, Star, Cyp11a1, Cyp21, Cyp11b1, Cyp11b2, Nr5a1, Nr4a1, and Nr4a2) and proteins, and antioxidant enzymes (Sod1, Sod2, Gpx1, and Cat) and their proteins, while up-regulating the expression of Mc2r and Agtr1a at various doses. BBOP reduced the phosphorylation of AKT1, AKT2, and ERK1/2, as well as the levels of SIRT1 and PGC1α without affecting the phosphorylation of AMPK. BBOP significantly induced the production of reactive oxygen species and apoptosis rate in H295R cells at 100 μM and higher after 24 h of treatment. In conclusion, male rats exposed to BBOP in puberty have significant reduction of steroid biosynthesis with a potential mechanism that is involved in the decrease in the phosphorylation of AKT1, AKT2, ERK1/2, as well as SIRT1 and PGC1α and increase in ROS.

Background: To determine risk factors for intestinal necrosis in intussusception cases among children with failed non-surgical reduction for intussusception.Methods: Totally, 540 hospitalized individuals with unsuccessful air-enema reduction in our hospital between November 2010 and November 2020 were assessed in this retrospective study. The 540 intussusception cases were divided into the intestinal necrosis and non-intestinal necrosis groups. Haemostatic parameters, demographic and clinical features were assessed. Predictors of intestinal necrosis were examined by univariable and multivariable logistic regression analyses.Results: Of the 540 patients included, 113 showed intestinal necrosis. This intestinal necrosis group had a longer duration of symptom or length of illness, younger ages, higher platelet counts, fibrinogen amounts and D-dimer levels (all P = 0.000) compared with the nonintestinal necrosis group. Multivariable analysis revealed that duration of symptom (odds ratio (OR) 1.12; 95% confidence interval (CI) 1.16-1.23, P = 0.000), fibrinogen (OR 1.26; 95% CI 1.10-1.31, P = 0.010) and D-dimer (OR 2.07; 95% CI 1.91-2.28, P = 0.000) independently predicted intestinal necrosis in individuals undergoing surgical reduction for intussusception. Receiver operating characteristic curve analysis showed that D-dimer amounts had the largest area under the curve for predicting intestinal necrosis.Conclusion: On admission, long duration of symptom, high fibrinogen and D-dimer levels are critical risk factors for intestinal necrosis development in children with unsuccessful non-surgical reduction. D-Dimer levels have the best predictive value for intestinal necrosis.

Background： Aldolase B (ALDOB) is a member of the aldolase family, which is the fourth enzyme in glycolysis process. In recent years, the non-enzymatic effects of some glycolytic enzymes have been reported to promote the formation of several human tumors, but the non-enzymatic action of ALDOB in neuroblastoma(NB) remains unclear. This study aims to explore the non-enzymatic effect of ALDOB in neuroblastoma. Methods： We used immunohistochemistry to examine 63 patients tissue microarray samples and 3 pairs of lymph node metastases and the primary tissue samples, and evaluated the relationship between ALDOB expression level and clinical characteristics. We then analyzed the public datasets of NB based on microarray to verify the immunohistochemistry results. In addition, we conducted in vitro experiments on SK-N-BE(2) and SH-SY5Y cell lines to explore the molecular mechanism. Results： Immunohistochemistry indicated ALDOB is significantly associated with INSS stage and tumor metastasis in NB, public dataset analysis showed ALDOB is related to NB patient survival remarkably. In vitro experiments displayed silencing ALDOB may inhibit the cell migration by epithelial-mesenchymal transition (EMT) pathway. Conclusions： Our finding demonstrated that ALDOB can affect the metastasis of NB by EMT pathway and may be a potential target for neuroblastoma therapy in the future.

Phthalates as plasticizers are widely used in many consumer products. Dipentyl phthalate (DPeP) is one of phthalates. However, there are currently few data on whether DPeP exposure affects rat Leydig cell development. In this study, we investigated the effects of in utero DPeP exposure on Leydig cell development in the testes of male newborn and adult rats. From gestational days 14 to 21, Sprague-Dawley pregnant rats were gavaged vehicle (corn oil, control) or DPeP (10, 50, 100, and 500 mg/kg body weight/day). Testosterone and the expression of Leydig cell genes and proteins in the testis at birth and at postnatal day 56 were examined. DPeP dose-dependently reduced serum testosterone levels of male offspring at birth and at postnatal day 56 at 100 and 500 mg/kg and lowered serum luteinizing hormone levels at adult males at ≥10 mg/kg when compared with the control. In addition, DPeP increased number of fetal Leydig cells by inducing their proliferation but down-regulated the expression of Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, Cyp17a1, Hsd17b3, and Insl3 in fetal Leydig cells per se. DPeP reduced number of adult Leydig cells by inducing cell apoptosis and down-regulated the expression of Lhcgr and Star in adult Leydig cells at postnatal day 56. DPeP lowered SIRT1 and BCL2 levels in the testis of adult rats. In conclusion, DPeP adversely affects both fetal and adult Leydig cell development after in utero exposure.

儿童肾细胞癌(RCC)较少见,其中5岁以上儿童相对多见,早期多无症状,病理组织学类型与成人有所不同,MiT家族易位型RCC是儿童RCC最常见的病理类型.儿童RCC尚无公认的血清学标志物,超声检查是筛查及术后随访的主要检查手段,CT检查具有较高的灵敏度和特异度,一般无需术前穿刺活检.不管儿童RCC为何种病理类型,根治性肾切除术是标准的手术方式,局限性RCC通过手术切除即可获得良好的预后,不需要其他辅助治疗.保留肾单位手术/肾部分切除术在儿童RCC中已得到开展,但是否需要进行根治性淋巴结清扫尚有争议.本文对儿童RCC诊治现状作一述评,内容包括儿童RCC的病理分型与临床分期、临床表现与诊断、治疗原则以及MiT家族易位型RCC等.

Phthalates are plasticizers widely found in the environment. They are potential endocrine disruptors. Bis (2-butoxyethyl) phthalate (BBOP) is a unique phthalate that contains oxygen atoms in the carbon backbone. Little is known about its reproductive and developmental toxicity. The objective of this study was to determine the effect of BBOP on fetal Leydig cell development after in utero exposure to rats. Sprague Dawley pregnant dams were randomly allocated into 6 groups, and were gavaged with BBOP (0, 10,100, 250, 500, and 1000 mg/kg body weight/day) from gestational day (GD) 14-21. Seven of the 8 dams in the 1000 mg/kg BBOP group died before giving birth. Twelve of the 20 dams in the 500 mg/kg BBOP group had whole litter loss. BBOP significantly reduced the body weight of dams and male offspring and serum testosterone level and anogenital distance of male fetus on GD 21 at 500 mg/kg. BBOP markedly increased fetal Leydig cell proliferation and number at 500 mg/kg while inducing their abnormal aggregation at 250 and 500 mg/kg. BBOP down-regulated the expression of Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, Cyp17a1, Hsd17b3, Insl3, and Nr5a1 at various doses while up-regulating the expression of Sertoli cell gene Fshr and Sox9. The phosphorylation of AKT1, AKT2, and ERK1/2 was also markedly reduced by BBOP. In conclusion, BBOP in utero exposure can disrupt fetal Leydig cell development, possibly via the mechanism that may include inhibiting the phosphorylation of AKT1, AKT2, and ERK1/2. (c) 2021 Elsevier B.V. All rights reserved.

Intestinal barrier dysfunction contributes to the development of intestinal diseases. Propionic acid (PA), a metabolite generated by anaerobic fermentation of dietary fiber in the intestinal cavity, has been proved to exert anti-inflammatory effects in a variety of diseases. However, the exact role of PA in LPS-induced intestinal barrier dysfunction is still unclear. Accordingly, we examined the latent mechanism of PA and its protective role in LPS-induced intestinal barrier dysfunction by both in vitro and in vivo experiments. In vitro, we identified that PA treatment could strongly promote cell migration, inhibit activation of NLRP3 inflammasome and maintain intestinal barrier function in LPS-induced IEC-6 cells, indicating the protective effect on the intestinal barrier function of PA. Further investigation of the mechanism involved revealed that PA could suppress the activation of TLR4/NF-κB pathway. In vivo, in a LPS-induced rat model, PA-induced protective effects in intestinal barrier dysfunction could be detected. In summary, our findings clarify the role of PA in intestinal barrier dysfunction and suggest that it is promising for the treatment of LPS-related intestinal diseases.

Purpose Congenital pyriform sinus fistula (CPSF) often presents diagnosis and treatment challenges. This study aimed to explore the treatment principles and to evaluate the effectiveness of the hypothermia plasma cauterization with suspension laryngoscopy for CPSF. Methods The medical records of 56 patients with CPSF from January 2000 to December 2019 were retrospectively reviewed. Results Of the 56 cases, the lesions were predominantly located on the left side (95%), and the accuracy of the first diagnosis was 30%. Ultrasound showed an abnormal rate of 86%, while CT or MRI displayed an abnormal anatomic lesion of 92%. The 3D visual reconstruction enabled the analysis of morphological characteristics of CPSF. The positive predictive value of barium esophagography was 89%, whereas the positive rate of the internal opening in CPSF under local anesthesia laryngoscopy was 33%. Nine cases of sinus type underwent open resection, and the recurrence rate was 33%. Interestingly, ten patients with sinus type underwent hypothermia plasma cauterization with suspension laryngoscopy, leading to a success rate of 100% without apparent complications. Conclusions Hypothermia plasma cauterization with suspension laryngoscopy alongside 3D imaging is both minimally invasive and repeatable with neglectable complications, which has the potential to serve as the first-line treatment for CPSF in the future.

Objective:Researches have demonstrated that physiological concentrated of sodium butyrate plays an important role in promoting intestinal barrier function while an excessive level of sodium butyrate is correlated with the occurrence of neonatal necrotizing enterocolitis (NEC). However, the underlying mechanism has remained elusive. Here the authors explored the effect of high-concentration sodium butyrate on monolayer Caco-2 cell model of intestinal barrier and examine the effect of nuclear factor-kappa B (NF-κB) pathway on this process for elucidating the possible molecular mechanisms of high-concentration sodium butyrate impairing intestinal epithelial barriers.Methods:Different concentrations of sodium butyrate and triptolide (NF-κB specific inhibitor, 50 nmol/L) were employed for Caco-2 cell monolayer model of intestinal barrier and Caco-2 cell in vitro. The transepithelial electrical resistance (TER) and the permeability of inulin-FITC were measured. The mRNA and protein levels of interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α ) were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot. Nuclear and cytosolic extracts of Caco-2 cells were isolated for analyzing the nuclear translocation of p65 by immunoblot.Results:After 72h incubation of high-concentration sodium butyrate (5/8 mmol/L), TERs declined while inulin-FITC permeability increased significantly as compared with control group. TER of 5 mmol/L sodium butyrate declined to (106.33±4.04 Ω×cm 2) and the permeability of inulin-FITC spiked to (12.52%±1.82%). Both were significantly different with control group. After inhibiting NF-κB with 50 nmol/L triptolide, TER increased to (398.33±3.06 Ω×cm 2) and the permeability of inulin-FITC declined to (7.24%±0.25%). And both were significantly different from high-concentration sodium butyrate (5 mmol/L) group. As compared with control group, after treating with high-concentration sodium butyrate (5/8 mmol/L), mRNA and protein levels of IL-1β and TNF-α and the level of nucleus p65 also significantly increased. Compared with 5 mmol/L sodium butyrate, triptolid, a NF-κB specific inhibitor, could significantly inhibit the nuclear entry of p65 and down-regulate the expressions of IL-1β and TNF-α . Conclusions:High-concentration sodium butyrate impairs intestinal barrier function and an activation of NF-κB pathway releases various inflammatory factors.

为探讨微信平台在小儿外科学业考核中的构建及运用,选取2017年9月至2019年6月在温州医科大学附属第二医院学习的小儿外科医学生共80人,随机分为实验组和对照组,每组各40人;考核试卷分为微信版(A卷)与传统纸质版(B卷),实验组行A卷考核,对照组行传统纸质版B卷考核,比较两组考试的耗时时间;实验组A卷考核结束后再行B卷传统考核,对实验组满意度进行调查.结果实验组有效地节省了人力和物力,缩短了无效时间,提高了考核工作效率,考生对此类考核形式较满意.可见,微信网络平台学业考核优点突出,考核公平公正,节省财力物力,工作效率和学生满意度高,值得运用推广.

Objective:To evaluate the effect of sodium butyrate (NaB) on the protection of intestinal barrier function and establish the effect of NaB on intestinal mucosa in neonatal rats.Methods:The 9-day-old neonatal rats were randomly divided into 5 groups. The serial concentrations of NaB were set at 20, 40, 80 and 160 mmol/L. And saline was selected as a normal control. Intestinal tissue was harvested after an ileal infusion of different concentrations of NaB for 1 hour. Transepithelial electrical resistance (TER) was measured on a Ussing chamber and pathological condition and inflammatory injuries were observed by hematoxylin-eosin stain. The expressions of tight junction proteins Occludin and ZO -1 mRNA were detected by real-time quantitative polymerase chain reaction (RT-qPCR), Occludin and ZO -1 protein levels were detected by Western blot.Results:(a) The value of TER (relative to initial value %) of control group at 30/60/120 min was (87.36±1.88), (85.98±0.99), (101.03±1.47) and 20 mmol/L group (83.45±2.97), (107.24±5.35), (101.44±3.96), 40 mmol/L group (126.07±3.48), (140.54±3.64), (100.50±4.64), 80 mmol/L group (102.24±4.60), (134.55±7.80), (106.76±8.82) and 160 mmol/L group (84.80±2.97), (78.16±2.89), (67.11±4.07) respectively. After acting with different concentrations of NaB for 30 min, as compared with control group, TER value of 40 mmol/L group increased markedly ( P<0.05), At 1 h, TER value of 40/80 mmol/L group was significantly higher than those of control and 20/160 mmol/L groups ( P<0.05). However, no significant inter-group difference existed ( P>0.05); (b) After reacting with different concentrations of sodium butyrate for 1 h, histologic injury scores was significantly higher in 160 mmol/L group than that in control group [(2.16±0.75) vs (0.33±0.51), P<0.01], other groups were not significant ( P>0.05); (c) 40/80 mmol/L group Occludin mRNA expression (1.80±0.31, 2.13±0.90) was higher than control group (1.01±0.21)( P<0.05) while protein level (0.58±0.04, 0.73±0.01) also increased as compared with control group (0.24±0.01) ( P<0.05). And ZO-1 mRNA expression (1.36±0.24, 1.45±0.58) was not significantly higher than that of control group (1.01±0.11) ( P>0.05). However, the level of protein (1.46±0.04, 1.34±0.07) was significantly higher than that of saline group (1.07±0.05) ( P<0.05). In addition, 160 mmol/L group Occludin and ZO -1 mRNA expression (1.27±0.47, 0.92±0.25) were insignificant ( P>0.05) while the protein expression levels (0.47±0.01, 2.90±0.04) were higher than that of control group ( P<0.01). Conclusions:NaB affects on intestinal barrier function in a time/dose-dependent manner. And 40/80 mmol/L sodium butyrate enhances intestinal mucosal barrier through the up-regulations of Occludin and ZO -1.