Multicenter investigation of pediatric gastrointestinal tract magnets ingestion in China.

PURPOSE: To describe the incidence and management of gastrointestinal tract Buckyball magnets ingestions in a multicenter Chinese pediatric patient population, and discuss the preventive measures. METHODS: Medical records of 74 pediatric patients from 9 large Chinese hospitals during the past 10 years, who were diagnosed as buckyball magnets ingestion and got invasive treatment, were retrospectively studied. The follow-up was through telephone and outpatient service to estimate the post-surgery condition. Information collection was through online questionnaire. RESULTS: Among the 74 cases, there were 50 boys (68%) and 24 girls (32%). The median age was 36 (interquartile range (IQR) 22-77) months, with a range of 7 months to 11 years, and it showed two peaks, the first between 1 and 3 years, and the second between 6 to 11 years. The annual case number showed a sharp increase over time, and the total case number in the last 2 years (2017 and 2018) showed a greater than 9-fold increase when compared with the first 2 years (2013 and 2014). The majority of ingestions were unintentional, with only 3 patients deliberately swallowing the Buckyball magnets. The median time of ingestion until the onset of emergent symptoms was 2 (IQR 1-5) days, and ranged from 4 h to 40 days. Twenty-one patients had no symptoms, and the remaining cases presented with abdominal pain, vomiting, fever, abdominal distension, excessive crying, melena, and the ceasing of flatus and defecation. Gastroscopy, colonoscopy, laparoscopic surgery and laparotomy surgery were performed in accordance with the algorithm from the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN). Procedural and operative findings included gastrointestinal mucosa erosion, ischemia and necrosis, perforation, and abdominal abscess, fistula and intestinal obstruction. The median number of Buckyball magnets ingested was 4 (IQR 2-8), with a range from 1 to 39. During the median follow-up period of 6 (IQR 1-15) months, 3 patients had intestinal obstruction, and one underwent a second operation. The remaining 71 patients courses were uneventful during the follow-up period. None of the 74 patients reported a second swallowing of foreign bodies. CONCLUSIONS: The incidence of pediatric gastrointestinal tract magnets ingestion in China is increasing. Management of such patients should follow the NASPGHAN algorithm. Preventive measures to limit children's access to Buckyball magnets should be taken from three levels, namely the national administration, producer, and consumer.

Screening and identification of non-inflammatory specific protein markers in Wilms' tumor tissues.

Wilms' tumor is one of the most common malignancies in children, and early diagnosis is critical for its subsequent treatment and prognosis. Our previous study employed proteomics to investigate protein markers in the serum of Wilms' tumor children. The present study aimed to identify specific protein markers in Wilms' tumor. Proteomic comparison of Wilms' tumor with normal kidney tissues and the sera of systemic inflammatory response syndrome (SIRS) controls was performed. Surface-enhanced laser desorption ionization time-of-flight (SELDI-TOF-MS) identified a protein with m/z 8350 as specific to Wilms' tumor. The target protein was purified using sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) and identified as profilin-1 by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF). Its expression was validated using real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Our data identify profilin-1 as a potential protein marker for Wilms' tumor and demonstrate the feasibility of the above procedures for screening and identification of tumor-specific protein markers.

Diagnostic and prognostic role of serum protein peak at 6449 m/z in gastric adenocarcinoma based on mass spectrometry.

BACKGROUND: Gastric cancer (GC) is a highly aggressive cancer type associated with significant mortality owing to delayed diagnosis and non-specific symptoms observed in the early stages. Therefore, identification of novel specific GC serum biomarkers for screening purposes is an urgent clinical requirement. METHODS: This study recruited a total of 432 serum samples from 296 GC patients split into the mining and testing sets. We aimed to screen for reliable protein biomarkers from matched serum samples based on mass spectrometry, followed by comparison with three representative conventional markers using receiver operating characteristic and survival curve analyses to ascertain their potential values as diagnostic and prognostic biomarkers for GC. RESULTS: We identified an apoC-III fragment with confirmation in an independent test set from a second hospital. We found that the diagnostic ability of this fragment performed better than current standard GC diagnostic biomarkers both individually and in combination in distinguishing patients with GC from healthy individuals. Moreover, we found that this apoC-III protein fragment represents a more robust potential prognostic factor for GC than the three conventional markers. CONCLUSIONS: In view of these findings, we suggest that apoC-III protein fragment is a novel diagnostic and prognostic biomarker, a complement to conventional biomarkers in detecting GC.

Assessment of promoter methylation and expression of SIX2 as a diagnostic and prognostic biomarker in Wilms' tumor.

This study was designed to evaluate the utility of expression and DNA methylation patterns of the sine oculis homeobox homolog 2 (SIX2) gene in early diagnosis and prognosis of Wilms' tumor (WT). Methylation-specific polymerase chain reaction (MSP), real-time quantitative polymerase chain reaction (qRT-PCR), receiver operating characteristic (ROC), and survival curve analyses were utilized to measure the expression and DNA methylation patterns of SIX2 in a cohort of WT tissues, with a view to assessing their diagnostic and prognostic value. Relative expression of SIX2 mRNA was higher, while the promoter methylation level was lower in the WT than control group (P < 0.05) and closely associated with poor survival prognosis of WT children (P < 0.05). Increased expression and decreased methylation of SIX2 were correlated with increasing tumor size, clinical stage, vascular invasion, and unfavorable histological differentiation (P < 0.05). ROC curve analysis showed areas under the curve (AUCs) of 0.579 for methylation and 0.917 for expression in WT venous blood, indicating higher diagnostic yield of preoperative SIX2 expression. The preoperative venous blood SIX2 expression level serves as an underlying biomarker for early diagnosis of WT. SIX2 overexpression and concomitantly decreased promoter methylation are significantly associated with poor survival of WT children.

Identification of apolipoprotein C-I as a potential Wilms' tumor marker after excluding inflammatory factors.

Wilms' tumor is one of the most common malignant tumors observed in children, and its early diagnosis is important for late-stage treatment and prognosis. We previously screened and identified protein markers for Wilms' tumor; however, these markers lacked specificity, and some were associated with inflammation. In the current study, serum samples from children with Wilms' tumors were compared with those of healthy controls and patients with systemic inflammatory response syndrome (SIRS). After exclusion of factors associated with inflammation, specific protein markers for Wilms' tumors were identified. After comparing the protein peak values obtained from all three groups, a protein with a m/z of 6438 Da was specified. Purification and identification of the target protein using high-pressure liquid chromatography (HPLC) and two-dimensional liquid chromatography-linearion trap mass spectrometry(2D-LC-LTQ-MS) mass spectrometry, respectively, revealed that it was apolipoprotein C-I (APO C-I). Thus, APO C-I is a specific protein marker for Wilms' tumor.

METTL3 promotes the progression of osteosarcoma through the N6-methyladenosine modification of MCAM via IGF2BP1.

BACKGROUND: The molecular mechanisms of osteosarcoma (OS) are complex. In this study, we focused on the functions of melanoma cell adhesion molecule (MCAM), methyltransferase 3 (METTL3) and insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) in OS development. METHODS: qRT-PCR assay and western blot assay were performed to determine mRNA and protein expression of MCAM, METTL3, IGF2BP1 and YY1. MTT assay and colony formation assay were conducted to assess cell proliferation. Cell apoptosis, invasion and migration were evaluated by flow cytometry analysis, transwell assay and wound-healing assay, respectively. Methylated RNA Immunoprecipitation (MeRIP), dual-luciferase reporter, Co-IP, RIP and ChIP assays were performed to analyze the relationships of MCAM, METTL3, IGF2BP1 and YY1. The functions of METTL3 and MCAM in tumor growth were explored through in vivo experiments. RESULTS: MCAM was upregulated in OS, and MCAM overexpression promoted OS cell growth, invasion and migration and inhibited apoptosis. METTL3 and IGF2BP1 were demonstrated to mediate the m6A methylation of MCAM. Functionally, METTL3 or IGF2BP1 silencing inhibited OS cell progression, while MCAM overexpression ameliorated the effects. Transcription factor YY1 promoted the transcription level of METTL3 and regulated METTL3 expression in OS cells. Additionally, METTL3 deficiency suppressed tumor growth in vivo, while MCAM overexpression abated the effect. CONCLUSION: YY1/METTL3/IGF2BP1/MCAM axis aggravated OS development, which might provide novel therapy targets for OS.

[Expression and promoter methylation of SIX2 gene in peripheral blood of pediatric patients with nephroblastoma].

OBJECTIVE: To explore the transcriptional expression and promoter methylation status of SIX2 gene in peripheral blood of pediatric children with nephroblastoma and discuss their clinicopathological correlations. METHODS: Approved by the hospital ethics committee, peripheral blood samples were collected from 45 children with Wilms' tumor(case group) at the Department of Pediatric Surgery, First Affiliated Hospital, Zhengzhou University from October 2008 to January 2012. And another 15 pediatric cases gender-and-age matched, were selected as the control group (excluding cancer and other malignant diseases). The real-time quantitative (qRT)-PCR and methylation-specific PCR (MSP) were used to detect the mRNA expression level and methylation status of SIX2 gene.t or χ(2) test were used. Then analyzed their clinicopathological correlations in the case group and how SIX2 gene methylation affected its transcription. RESULTS: Relative quantity(RQ) of SIX2 mRNA in the case group was higher than that of the control group (1.93 ± 1.10 vs 0.57 ± 0.39, t = 5.354, P = 0.000). There were 8 SIX2 gene methylation-positive cases in the case group versus 12 cases in the control group. And the methylation positive ratio was extremely lower in the case group (χ(2) = 19.600, P = 0.000). RQ values in the case group was associated with tumor size, clinical stage, pathological type, lymph node metastasis, treatment and outcome (all P < 0.05). RQ values in the methylated group was lower than that of the unmethylated group both in case and control group (1.35 ± 0.44 vs 1.95 ± 1.15, 0.43 ± 0.29 vs 1.13 ± 0.20, t = 2.459 and 3.896, P = 0.020 and 0.002) . RQ values of case group was higher than that of the control group in methylated group (t = 5.624, P = 0.000) . No statistical significance existed in RQ values between the case and control groups of unmethylated group (t = 1.222, P = 0.229) . CONCLUSIONS: A close correlation between SIX2 low methylation and high mRNA expression in blood suggests that aberrant promoter methylation is possibly one of gene expression regulations, and may be correlated with the occurrence and development of Wilms' tumor. And SIX2 gene in methylated Wilms' tumor may play the role of oncogenes. A negative correlation exists between the overexpression in transcriptional level and its methylation status.

[Relationship between mRNA expression and promoter methylation status of p73 gene in peripheral blood among children with Wilms' tumor].

OBJECTIVE: To investigate the mRNA expression and promoter methylation status of p73 gene in the peripheral blood of children with Wilms' tumor (WT), and their relationship. METHODS: Forty-five children with WT were selected as the case group, and 15 sex- and age- matched children (without malignancies) who visited the hospital for physical examination or other reasons were selected as the control group. Peripheral blood was collected from both groups. Real-time quantitative PCR and methylation-specific PCR were used to determine the mRNA expression level and promoter methylation status of p73 gene. Their relationship with clinicopathological features and the effect of promoter methylation on mRNA expression of p73 gene were analyzed in the case group. RESULTS: The relative quantity (RQ) of p73 mRNA in the case group was significantly higher than in the control group (3.2 ± 0.9 vs 1.6 ± 1.1; P<0.01). The positive rate of p73 gene promoter methylation in the case group was significantly lower than in the control group (20% vs 73%; P<0.01). In the case group, the RQ of p73 mRNA was significantly higher in children with methylated p73 gene promoter than in those with unmethylated p73 gene promoter (P<0.01). In children with methylated p73 gene promoter, the RQ of p73 mRNA was significantly higher in the case group than in the control group (P<0.01). In children with unmethylated p73 gene promoter, there was no significant difference in RQ of p73 mRNA between the case and control groups (P=0.810). CONCLUSIONS: Aberrant promoter methylation of p73 gene in peripheral blood is one of the gene expression regulations in children with WT, and it is related to the onset and development of WT. The p73 gene may play a role as oncogene in WT patients with p73 gene promoter methylation and mRNA overexpression is associated with promoter methylation status of p73 gene.

Screening of undernutrition in children with Hirschsprung disease using preoperative anthropometric parameters: A multicenter cross-sectional study.

BACKGROUND: The prevalence of malnutrition is unknown in patients with Hirschsprung disease. Undernutrition is associated with poor clinical outcomes. This study aims to describe the nutrition status among patients with Hirschsprung disease at admission. METHODS: We retrospectively used data from children with Hirschsprung disease admitted to three pediatric surgery centers in China from January 2016 to December 2020. The weight-for-age z scores (WAZ), height-for-age z scores (HAZ), and body mass index-for-age z scores (BAZ) were calculated as the reference for nutrition risk according to the World Health Organization child growth standards. The nutrition status of enrolled children was described and nutrition risk in each clinical characteristic was compared. The association between nutrition status and clinical outcomes was analyzed using univariate and multivariate logistic regression. RESULTS: A total of 624 patients were included in this study. The mean WAZ, HAZ, and BAZ of all patients was -0.64 ± 1.40, -0.45 ± 1.78, and -0.43 ± 1.50, respectively. Moderate to severe overall undernutrition was 16.3% (102/624). We found that WAZ and BAZ were significantly reduced with the length of aganglionic segments (P = 0.001). Children who had a definitive surgery at 3 years of age or older had significantly lower HAZ (P = 0.001). A multivariate regression model assessing postoperative Hirschsprung-associated enterocolitis showed that the WAZ was one of the independent risk factors (P = 0.001). CONCLUSION: Undernutrition is prevalent among children with Hirschsprung disease. Nutrition assessment to identify individuals at risk of undernutrition for further intervention is necessary.

Severity assessment to guide empiric antibiotic therapy for cholangitis in children after Kasai portoenterostomy: a multicenter prospective randomized control trial in China.

BACKGROUND: Cholangitis is common in patients with biliary atresia following Kasai portoenterostomy (KPE). The prompt use of empiric antibiotics is essential due to the lack of identified microorganisms. The authors aimed to validate a severity grading system to guide empiric antibiotic therapy in the management of post-KPE cholangitis. MATERIALS AND METHODS: This multicenter, prospective, randomized, open-label study recruited patients with post-KPE cholangitis and was conducted from January 2018 to December 2019. On admission, patients were categorized into mild, moderate, and severe cholangitis according to the severity grading system. Patients in the mild cholangitis group were randomized to receive cefoperazone sodium tazobactam sodium (CSTS) or meropenem (MEPM). Patients with severe cholangitis were randomized to treatment with MEPM or a combination of MEPM plus immunoglobulin (MEPM+IVIG). Patients with moderate cholangitis received MEPM. RESULTS: The primary endpoint was duration of fever (DOF). Secondary outcomes included blood culture, length of hospital stay, incidence of recurrent cholangitis, jaundice clearance rate, and native liver survival (NLS). For mild cholangitis, DOF, and length of hospital stay were similar between those treated with CSTS or MEPM (all P >0.05). In addition, no significant difference in recurrence rate, jaundice clearance rate, and NLS was observed between patients treated with CSTS and MEPM at 1-month, 3-month, and 6-month follow-up. In patients with moderate cholangitis, the DOF was 36.00 (interquartile range: 24.00-48.00) h. In severe cholangitis, compared with MEPM, MEPM+IVIG decreased DOF and improved liver function by reducing alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and direct bilirubin at 1-month follow-up. However, recurrence rate, jaundice clearance rate, and NLS did not differ significantly between MEPM+IVIG and MEPM at 1-month, 3-month, and 6-month follow-up. CONCLUSIONS: In patients with post-KPE cholangitis, MEPM is not superior to CSTS for the treatment of mild cholangitis. However, MEPM+IVIG treatment was associated with better short-term clinical outcomes in patients with severe cholangitis.

Inflammation-related pathways involved in damaged articular cartilage of rats exposed to T-2 toxin based on RNA-sequencing analysis.

Many studies have shown that ingestion of the T-2 toxin is harmful to articular cartilage. However, the mechanisms underlying damaged articular cartilage induced by T-2 toxin have not been elucidated. Twenty-four SD rats were randomly divided into T-2 toxin and control groups. In the control group, the 12 rats were administered 4% absolute ethanol by gavage, and in the T-2 toxin group, the 12 rats were administered T-2 toxin (100 ng/g, BW/day) by gavage. After the rats were sacrificed, the knee joints were collected, and RNA was extracted using TRIzol reagent for RNA sequencing (RNA-seq). Differentially expressed mRNA was identified based on p < 0.05 and | log2 (fold change) | > 1. The T-2 toxin-related genes were obtained from the GeneCards database. An online tool (https://www.bioinformatics.com.cn) was used for enrichment analysis. Hematoxylin and eosin (H&E) staining was used to observe damaged articular cartilage, and immunohistochemical (IHC) staining was used to validate differentially expressed proteins. The H&E staining shows the number of cells decreased significantly, and the arrangement of chondrocytes became disordered in the T-2 toxin group. RNA-seq analysis identified 195 upregulated and 89 downregulated mRNAs in the T-2 toxin group. The top immune-related biological processes (Gene Ontology) were regulation of hormone secretion, regulation of peptide hormone secretion, and regulation of transcription involved in cell fate commitment. KEGG pathway enrichment analysis revealed that the IL-17 and tumor necrosis factor signaling pathways were significantly expressed, and the IL-17 signaling pathway was also identified in the enrichment analysis of T-2 toxin-related genes. Also, Mmp3, Tnf, Mapk10, Ccl11, Creb5, Cxcl2, and Cebpb were significantly enriched in the two pathways. The immunohistochemical staining showed that the levels of Mmp3 and Tnf proteins were significantly increased in the T-2 toxin group, which was consistent with the RNA-seq results. This study revealed the critical roles of IL-17 and TNF signaling pathways in damaged cartilage induced by T-2 toxin.

The safety and effectiveness of Santulli enterostomy in neonatal intestinal conditions.

Background: As an end stoma, Santulli enterostomy provides early restoration of intestinal continuity without formal laparotomy. Short amputation of the common limb enables closure on a side to restore anatomic continuity without sacrificing valuable intestine; additionally, the procedure is simple and safe. Most newborns who require enterostomy might benefit from Santulli enterostomy; however, several pediatric surgeons lack information regarding this procedure. Therefore, we have reviewed our experience about Santulli enterostomy and explore the advantages and indications in neonatal intestinal conditions. Methods: The clinical data of 76 neonates who underwent enterostomywere obtained. The patients were divided into two groups: the Santulli group with 33 cases who underwent Santulli enterostomy, and the control group with 43 cases who underwent double- or single-lumen ostomy. The general data of the two groups were analyzed, and the perioperative/postoperative complications, clinical data and the long-term outcomes were compared. Results: There was no difference in the demographic informations, the level of enterostomy, the rate of high-sight stoma, the operative time and bleeding of enterostomy between the two groups. Compared to the control group, the operative time of ostomy closure was less in the Santulli group (53.00 vs. 152.47, P < 0.001). The duration of parenteral nutrition (27.45 vs. 44.56, P = 0.010), the mean interval of initial enterostomy to stomal closure (131.21 vs. 216.42, P < 0.001), and length of stay (46.00 vs. 67.60, P = 0.007) were shorter, while the incidence of postoperative complications and hospitalization costs (11.21 vs. 15.49, P = 0.006) were lower. The Santulli procedure can reduce the morbidity of high output ostomy (2 vs. 10, P = 0.042) and short bowel syndrome (3 vs. 132, P = 0.025), shorten the discrepancy of diameter between the proximal and distal segments, maximize the available intestine, and monitor the movement of the distal bowel. The length of incision was shorter, and the catch-up growth was significantly faster in the Santulli group. Conclusion: Santulli enterostomy is a superior procedure in the treatment of neonatal intestinal conditions, in terms of fewer complications, faster catch-up growth, shorter hospitalization time and treatment duration. It should be the procedure of choice in several newborns with intestinal conditions that require ostomy.

Enterocolitis Is a Risk Factor for Bowel Perforation in Neonates With Hirschsprung's Disease: A Retrospective Multicenter Study.

BACKGROUND AND AIM: We evaluated the clinical features of neonatal Hirschsprung's disease (HD)-associated bowel perforation (perforated HD) and investigated risk factors related to it. METHODS: We retrospectively collected clinical data of neonates (<1 month of age) with perforated HD from multicenters in China from January 2006 to December 2019. A total of 142 patients (6.7%) with perforated HD were enrolled in the study. A 1:2 matching method was used to compare the clinical information of HD patients with and without bowel perforation during the neonatal period. The risk factors for bowel perforation were identified using univariate and multivariate logistic risk regression analyses. RESULTS: Perforation site was present in the proximal ganglionic bowel in 101 (71.1%) cases and the distal aganglionosis segment in 41 (28.9%) cases. Adjacent marginal tissue from the perforated intestine revealed varying degrees of inflammatory cell infiltration, and the severity of enterocolitis was higher in the proximal ganglionic bowel than in the distal aganglionosis segment (p < 0.05). In the univariable and multivariable logistic analyses, clinical symptoms, such as vomiting (adjusted OR = 2.06, 95% CI: 2.01-2.88, p < 0.05), and inflammation index in hematologic tests, such as neutrophil proportion (adjusted OR = 1.09, 95% CI: 1.05-1.33, p < 0.05) and CRP (adjusted OR = 2.13, 95% CI: 1.01-3.27, p < 0.05) were associated with increased risk for perforated HD. CONCLUSION: Clinical Hirschsprung disease-associated enterocolitis (HAEC) highly correlated with perforated HD. Timely treatment of HAEC should be appropriate therapeutic approaches to prevent perforated HD.

The double-stranded RNA-dependent protein kinase inhibitor alleviates endoplasmic reticulum stress and alleviates sepsis-induced renal injury.

The double-stranded RNA-dependent protein kinase (PKR) is involved in inflammatory cytokine expression and disease pathogenesis in many conditions. The aim of this study was to explore the role of PKR in sepsis-induced renal tissue injury. Six-week-old C57BL/6J mice received PKR inhibitor (imoxin) and Endoplasmic reticulum (ER) inducer (tunicamycin) 2 hr prior to induction of inflammation via cecal ligation and puncture (CLP). Renal tissues were collected 24 hr after the CLP treatment and protein expression were assessed. The expression of creatinine (Cre) and blood urea nitrogen (BUN) in serum and inflammation factor in tissues was detected by ELISA, and the apoptosis of renal tissue was detected by TUNEL staining. PKR inhibitors reduce the expression of sepsis-induced ER stress in renal tissue, as well as the pathological changes and renal impairment in renal tissue. PKR inhibitors reduce the expression of sepsis-induced inflammatory response and sepsis-induced apoptosis in renal tissue by ER stress. In conclusion, PKR inhibitor alleviates ER stress and alleviates sepsis-induced renal injury.

The Efficacy of Biofeedback Therapy for the Treatment of Fecal Incontinence After Soave Procedure in Children for Hirschsprung's Disease.

Introduction: Hirschsprung's disease is a common digestive tract malformation in children, and the Soave procedure is one of the classic surgical methods for Hirschsprung's disease (HD). Fecal incontinence is one of the most common postoperative complications that can cause significant distress to the patients and their family, the incidence of which is 20% in a recent series. Biofeedback therapy (BFT) can be an effective treatment for managing anorectal disorders, but there has been little report of the efficacy of BFT for the treatment of fecal incontinence after the Soave procedure, and the main objective of this study is to evaluate it. Methods: We retrospectively analyzed postoperative fecal incontinence in 46 children who received the Soave procedure for HD and who received BFT at our institution from March 2016 to February 2020, which included 38 males and 8 females (mean age 8.1 years, from 3.7 to 14 years). Anal sphincter contraction training was performed using BFT for 10 days per session in the hospital, one time each day, and 20 min each time. BFT was performed by employing visual and verbal feedback techniques using the biofeedback instrument. Long-term functional outcomes were objectively assessed using the Rintala Bowel Function Score (RBFS), and the patients were scored according to the sum total as excellent (18-20 points, 0 case), good (11-16 points, 0 case), fair (9-11 points, 9 cases), or poor (6-9 points, 37 cases). Defecation questionnaires and anorectal manometry were completed pretreatment and after three, six, or nine sessions, and primary outcome measures of anorectal manometry were anal maximal contraction pressure (AMCP), anal longest contraction time (ALCT), rectal rest pressure (RRP), and anal rest pressure (ARP). Results: Followed up from 6 months to 4 years, the symptoms of fecal incontinence disappeared completely in 39 (84.78%) patients. Among them, 14 (30.43%) had complete disappearance of symptoms after 3 sessions of treatment, 25 (54.34%) patients had improved symptoms after 6 sessions of treatment, symptoms completely disappeared after 6 sessions of treatment, and 7 (15.22%) cases still suffered fecal incontinence mildly. The AMCP after three and six sessions in the poor group was significantly increased compared with that before treatment [(85.87 ± 31.75) mmHg vs. (135.33 ± 37.69) mmHg vs. (128.41 ± 33.45) mmHg, P < 0.05]. The ALCT and ARP showed the same trend, while the RRP after three and six sessions were not significant (P > 0.05). The mean (±SD) score of the RBFS increased from 9 to 17.40 ± 0.84 in the fair group, while it increased from 7.22 ± 0.76 to 16.58 ± 1.66 in the poor group after six sessions (P < 0.05). Conclusion: Biofeedback therapy is a safe and effective treatment of fecal incontinence after the Soave procedure of children for Hirschsprung's disease. It is beneficial to design the individualized treatment programs for the children with varying degrees of fecal incontinence.

Effectiveness and safety of ultrasound-guided hydrostatic reduction for children with acute intussusception.

OBJECTIVE: This study aims to explore the effectiveness and safety of the new-type ultrasound-guided hydrostatic reduction for children with acute intussusception. METHODS: The clinical data of 364 children with primary acute intussusception who underwent nonsurgical reduction in our hospital between January 2016 and May 2019 were retrospectively analyzed. Among the 364 children, 119 formed the hydrostatic reduction group. There were 89 males and 30 females, and the average age of admission was 25.13 ± 1.43 months. Among the pneumatic reduction group of 245 patients, there were 163 males and 82 females. The average age of admission was 22.47 ± 1.52 months. The reduction rate, length of stay, and perforation rate were compared between the two groups. RESULTS: Univariate analysis showed that the reduction rate in the hydrostatic group (94.96%) was higher than in the pneumatic group (85.31%) (p = 0.007), and the hospital stay (2.76 ± 0.15 days) of the hydrostatic reduction group was shorter than that of the pneumatic reduction group (3.56 ± 0.35 days) (p = 0.038). In children with intussusception time >48 h, the reduction rate was 95.45% in the hydrostatic reduction group and 86.20% in the pneumatic reduction group. CONCLUSION: The new-type ultrasound-guided hydrostatic reduction has a higher reduction rate in the treatment of acute intussusception in children results in a shortened hospital stay, It is effective, safe, and avoids radiation exposure.

Comparison of efficacy and safety of corticosteroid and vincristine in treating kaposiform hemangioendothelioma and tufted angioma: A multicenter prospective randomized controlled clinical trial.

Kaposiform haemangioendothelioma (KHE) and tufted angioma (TA) are rare vascular tumors that can cause life-threatening Kasabach-Merritt phenomenon. No evidence-based treatment strategies have yet been established, and its management is still a challenge. The purpose of this multicenter prospective randomized controlled study was to evaluate and compare the efficacy of corticosteroid and vincristine (VCR) in the treatment of KHE and TA. All patients with KHE/TA who met the diagnostic criteria were consecutively recruited. The patients were randomized into a methylprednisolone (MP) group and a VCR group. The primary outcome was the single main parameter effective rate and overall effective rate of corticosteroid and VCR over 1 month after treatment. The single main parameters included platelets, fibrinogen, tumor size, texture, and appearance. From May 2016 to April 2018, a total of 59 patients completed the clinical trial, including 29 in the MP group and 30 in the VCR group. The results showed that VCR was superior to corticosteroid in the improvement of platelet (80.0% vs 44.0%, P = 0.019) and tumor texture (68.9% vs 30.8%, P = 0.007). Although the efficacy of VCR on fibrinogen (23.3% vs 20.7%, P = 1.000), tumor size (23.3% vs 13.8%, P = 0.273), and appearance (65.5% vs 46.2%, P = 0.120) was higher than that of corticosteroid, there was no significant difference (P > 0.05). Meanwhile, the overall effective rate of VCR was higher than that of corticosteroid (56.7% vs 31.0%), but the difference was also not statistically significant (P = 0.067). In conclusion, the therapeutic effect of VCR was significantly better than that of corticosteroid with regard to treating thrombocytopenia and tumor texture. We recommend that VCR could be an option for first-line treatment in KHE/TA patients.

Standards of care for Kasabach-Merritt phenomenon in China.

Kasabach-Merritt phenomenon (KMP) is a rare disease that is characterized by severe thrombocytopenia and consumptive coagulation dysfunction caused by kaposiform hemangioendothelioma or tufted hemangioma. This condition primarily occurs in infants and young children, usually with acute onset and rapid progression. This review article introduced standardized recommendations for the pathogenesis, clinical manifestation, diagnostic methods and treatment process of KMP in China, which can be used as a reference for clinical practice.

Long non-coding RNA SNHG7 promotes neuroblastoma progression through sponging miR-323a-5p and miR-342-5p.

Dysregulation of long non-coding RNAs (lncRNAs) has been known to be relevant to the progression of human cancers, including neuroblastoma (NB). Small nucleolar RNA host gene 7 (SNHG7) has been identified as an oncogene in a series of human cancers. The purpose of the present study was to investigate the function and underlying mechanism of SNHG7 in NB progression. qRT-PCR was used to determine the levels of SNHG7, cyclin D1 (CCND1), miR-323a-5p and miR-342-5p. Cell migration and invasion abilities were detected by transwell assays. Glucose consumption and lactate production were assessed using the corresponding assay kits. The targeted interaction between SNHG7 and miR-323a-5p or miR-342-5p was verified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft tumor assays were performed to observe the effect of SNHG7 silencing on tumor growth in vivo. We found that SNHG7 was upregulated in NB tissues and cell lines, and high SNHG7 level was relevant to poor prognosis of NB patients. SNHG7 silencing resulted in the repression of NB cell migration, invasion and glycolysis. SNHG7 directly targeted miR-323a-5p and miR-342-5p and negatively modulated their expression in NB cells. The overexpression of miR-323a-5p or miR-342-5p weakened NB cell migration, invasion and glycolysis. Moreover, miR-323a-5p or miR-342-5p mediated the suppressive effect of SNHG7 silencing on NB cell progression. CCND1 was a direct target of miR-323a-5p and miR-342-5p. Additionally, SNHG7 knockdown repressed tumor growth in vivo. In conclusion, our study suggested that SNHG7 silencing hindered NB progression at least partly though sponging miR-323a-5p and miR-342-5p, illuminating its potential value as a therapeutic target.

Lysosomal dysfunction and autophagy blockade contribute to autophagy-related cancer suppressing peptide-induced cytotoxic death of cervical cancer cells through the AMPK/mTOR pathway.

BACKGROUND: Autophagy is an intracellular process through which intracellular components are recycled in response to nutrient or growth factor deficiency to maintain homeostasis. We identified the peptide autophagy-related cancer-suppressing peptide (ARCSP), a potential antitumor peptide that disrupts intracellular homeostasis by blocking autophagic flux and causes cytotoxic death. METHODS: The proliferative ability of ARCSP-treated cervical cancer cells was examined by the CCK8, EdU, and colony formation assays. The TUNEL assay was used to detect apoptosis. Mitochondrial function was evaluated based on the mitochondrial membrane potential. Autophagic flux was detected by immunofluorescence and confocal microscopy. The autophagy-related proteins AMPK, Raptor, mTOR, p62, LC3B, atg7, Rab7, LAMP1, LAMP2, and cathepsin D were detected by Immunoblotting. The antitumor effect of ARCSP was explored in vivo by establishing a transplant tumor model in nude mice. RESULTS: The results demonstrated that ARCSP induced cell death and inhibited proliferation. ARCSP induced AMPK/mTOR activation, resulting in the accumulation of the proteins LC3B, p62 and Atg7. ARCSP also blocked autophagosome-lysosome fusion by inhibiting endosomal maturation and increasing the lysosomal pH. The accumulation of nonfused autophagosomes exacerbated cytotoxic death, whereas knocking down Atg7 reversed the cytotoxic death induced by ARCSP. ARCSP-treated cells exhibited increased cytotoxic death after cotreatment with an autophagy inhibitor (Chloroquine CQ). Furthermore, the tumors of ARCSP-treated nude mice were significantly smaller than those of untreated mice. CONCLUSIONS: Our findings demonstrate that ARCSP, a novel lethal nonfused autophagosome inducer, might cause mitochondrial dysfunction and autophagy-related cytotoxic death and is thus a prospective agent for cancer therapy.