Chemoenzymatic Synthesis of GAA-7 Glycan Analogues and Evaluation of Their Neuritogenic Activities.

Ganglioside GAA-7 exhibits higher neurite outgrowth than ganglioside GM1a and most echinodermatous gangliosides (EGs) when tested on neuron-like rat adrenal pheochromocytoma (PC12) cells in the presence of nerve growth factor (NGF). The unique structure of GAA-7 glycan, containing an uncommon sialic acid (8-O-methyl-N-glycolylneuraminic acid) and sialic acid-α-2,3-GalNAc linkage, makes it challenging to synthesize. We recently developed a streamlined method to chemoenzymatically synthesize GAA-7 glycan and employed this modular strategy to efficiently prepare a library of GAA-7 glycan analogues incorporating N-modified or 8-methoxyl sialic acids. Most of these synthetic glycans exhibited moderate efficacy in promoting neuronal differentiation of PC12 cells. Among them, the analogue containing common sialic acid shows greater potential than the GAA-7 glycan itself. This result reveals that methoxy modification is not essential for neurite outgrowth. Consequently, the readily available analogue presents a promising model for further biological investigations.

Impact of Bariatric Surgery on Outcomes of Patients with Inflammatory Bowel Disease: a Nationwide Inpatient Sample Analysis, 2005-2018.

PURPOSE: The global prevalence of inflammatory bowel disease (IBD) has steadily risen over the past few decades. Bariatric surgery stands out as an effective strategy for inducing weight loss. This study investigated the impacts of bariatric surgery on the clinical outcomes in patients with IBD. MATERIALS AND METHODS: Data of hospitalized patients aged ≥ 18 years with IBD were extracted from the Nationwide Inpatient Sample (NIS) 2005-2018. The patients were categorized according to whether they underwent bariatric surgery or not. Univariate and multivariable logistic regression analyses were performed to determine the associations between bariatric surgery, prolonged LOS, unfavorable discharge, hospital mortality, and morbidity. RESULTS: Data from 807,843 hospitalized patients with IBD were extracted. After exclusions and propensity-score matching, 80,545 patients were analyzed, with 16,109 undergoing bariatric surgery and 64,436 not. A total of 23% of patients had a prolonged LOS, 8% had unfavorable discharge, and the mortality rate was 1.2%. Multivariable analyses revealed that, compared to patients without bariatric surgery, patients with bariatric surgery had significantly decreased odds of prolonged LOS (adjusted odds ratio [aOR], 0.89; 95% CI 0.85-0.93), unfavorable discharge (aOR, 0.83; 95% CI: 0.77-0.89), and mortality (aOR, 0.54; 95% CI: 0.44-0.67), but had increased odds of morbidity (aOR, 1.09; 95% CI 1.04-1.13). CONCLUSION: In adults with IBD, bariatric surgery is associated with favorable outcomes concerning hospital LOS, discharge status, and mortality. However, the risk of overall morbidity is slightly increased in those who received bariatric surgery compared to those who did not.

Comprehensive Analysis of Risk Factors for Bronchopulmonary Dysplasia in Preterm Infants in Taiwan: A Four-Year Study.

Bronchopulmonary dysplasia (BPD) is a major respiratory condition mainly affecting premature infants. Although its occurrence is global, risk factors may differ regionally. This study, involving 3111 infants with birth weight ≤ 1500 gm or gestational age (GA) < 30 weeks, aimed to identify risk factors for BPD and BPD/mortality in Taiwan using data from the Taiwan Neonatal Network. The BPD criteria were based on the National Institute of Child Health and Human Development standards. Average GA was 27.5 weeks, with 23.7% classified as small for GA (SGA). Multivariate analysis highlighted low GA, low birth weight, and other perinatal factors as significant risk indicators for BPD. For moderate-to-severe BPD, additional risk factors included male gender and SGA, endotracheal intubation (ETT) or cardiopulmonary cerebral resuscitation (CPCR) in initial resuscitation. In the moderate-to-severe BPD/death group, SGA and ETT or CPCR in initial resuscitation remained the only additional risk factors. The study pinpoints male gender, SGA and ETT or CPCR as key risk factors for moderate-to-severe BPD/death in low-birth-weight infants in Taiwan, offering a basis for focused interventions and further research.

Cystic artery pseudoaneurysm: A case report.

BACKGROUND: Cystic artery pseudoaneurysm is a condition rarely encountered by clinicians; this, its etiology and presentation as well as appropriate treatments are not well studied. Although it is treated by removal of the diseased gallbladder and cystic artery, such surgery can be difficult and risky if acute inflammation with bleeding occurs, and not every patient can tolerate the surgery. CASE SUMMARY: An 81-year-old man complained of epigastric pain and tarry stool passage that lasted for 3 d. He had a medical history of poor cardiopulmonary function. The computed tomographic scan of abdomen showed cystic artery pseudoaneurysm and dilatation of gallbladder. Because of high adverse outcomes related to general anesthesia, the patient was successfully managed with endovascular embolization for this cystic artery pseudoaneurysm and percutaneous drainage for the distended gallbladder. CONCLUSION: A patient with cystic artery pseudoaneurysm may quickly deteriorate with the occurrence of concurrent arterial bleeding and sepsis. This report presents the case of a patient who did not undergo surgery due to multiple cardiopulmonary comorbidities and whose condition was managed successfully with embolization and biliary drainage. Endovascular embolization and biliary drainage may provide an alternative option to manage this complicated condition.

Endoscopic full-thickness resection with retroperitoneal dissection for duodenal myogenic cyst with adjustable traction from an independently controlled snare.

Video 1Endoscopic full thickness resection with retroperitoneal dissection for duodenal myogenic cyst with adjustable traction from an independently controlled snare.

Uterine smooth muscle tumor of uncertain malignant potential: A review of current knowledge.

Uterine smooth muscle tumor of uncertain malignant potential is a subtype of uterine smooth muscle neoplasms. It is characterized by distinct pathologic findings with morphologic features intermediate between those of benign leiomyoma and malignant leiomyosarcoma. Clinically, STUMP is rare and its clinical picture is comparable to that of leiomyoma, with diagnosis typically being made postoperatively. Most patients with STUMP are uneventful after tumor resection. However, a small portion of patients may experience recurrence that may even lead to mortality. Given the uncommon occurrence of STUMP and the low frequency of malignant potential, currently there is still no standard guideline in treating patients with this disease and this can be challenging for physicians. Moreover, because cases are rarely available for study, investigating this tumor is difficult. Thus, matters such as the pathologic diagnostic criteria, strategy of clinical management, identification of prognostic factors, and the pathogenesis of this disease remain to be clarified. We collected and analyzed recently published case series studies of STUMP to obtain up-to-date clinical information. The current status of research in various basic and clinical aspects of this tumor was also reviewed.

Pneumatosis intestinalis after systemic chemotherapy for colorectal cancer: A case report.

BACKGROUND: Pneumatosis intestinalis (PI), also known as intramural gas in the small intestine, is a rare condition encountered by patients with cancer after receiving chemotherapy. CASE SUMMARY: A 78-year-old man with a history of colorectal cancer developed epigastric pain and diarrhea after receiving combination chemotherapy of fluorouracil, leucovorin, irinotecan, and cetuximab. Abdomen radiography revealed intramural air in the small intestinal wall. A computed tomography scan of the abdomen revealed the features of PI with air expanding into the mesentery. After surgery, the patient remained symptom-free throughout a 9 mo follow-up period during which he received chemotherapy of fluorouracil, leucovorin, and irinotecan. CONCLUSION: Although chemotherapy-induced PI is rare among patients with cancer, the differential diagnosis of PI and fulminant complications (such as ischemia, infarction, and perforation of the gastrointestinal tract) should be conducted, in which case an urgent surgical intervention is required.

Impact of Bariatric Surgery on Outcomes of Patients with Rheumatoid Arthritis: a Propensity Score-Matched Analysis of US Nationwide Inpatient Sample, 2005-2018.

PURPOSE: Obesity has been considered one of the risk factors with more critical disease progression and poor treatment response in rheumatoid arthritis (RA). We herein utilized an extensive, nationally representative database to examine the impact of bariatric surgery on clinical outcomes in RA patients. MATERIALS AND METHODS: This retrospective analysis utilized nationally representative data of the Healthcare Cost and Utilization Project-National Inpatient Sample database (HCUP-NIS) from 2005 to 2018. Associations between bariatric surgery and in-hospital outcomes of RA patients were determined by the univariate and multivariate logistic regression analyses. RESULTS: After 1:4 propensity score (PS) matching, totally 33,075 hospitalized adults with RA were included as primary cohort for subsequent analyses. Among them, 6615 patients had prior bariatric surgery and 26,460 patients had not. After adjusting for relevant confounders in the multivariate analysis, prior bariatric surgery was significantly and independently associated with reduced odds for any morbidity and in-hospital mortality (aOR: 0.41, 95% CI: 0.27-0.61, p < 0.01) as compared with no prior bariatric surgery. Adults with RA who had prior bariatric surgery also had a significantly lower odds for having unfavorable discharge and prolonged length of stay (LOS) as compared with those without bariatric surgery (aOR: 0.43, 95% CI: 0.39-0.46, p < 0.01). CONCLUSIONS: Prior bariatric surgery is associated with better in-patient outcomes among RA, including in-hospital mortality, major morbidities, discharge destination, and LOS.

Superoxide Initiates the Hyphal Differentiation to Microsclerotia Formation of Macrophomina phaseolina.

The infection of Macrophomina phaseolina often results in a grayish appearance with numerous survival structures, microsclerotia, on the plant surface. Past works have studied the development of fungal survival structures, sclerotia and microsclerotia, in the Leotiomycetes and Sordariomycetes. However, M. phaseolina belongs to the Dothideomycetes, and it remains unclear whether the mechanism of microsclerotia formation remains conserved among these phylogenetic clades. This study applied RNA-sequencing (RNA-Seq) to profile gene expressions at four stages of microsclerotia formation, and the results suggested that reactive oxygen species (ROS)-related functions were significantly different between the microsclerotia stages and the hyphal stage. Microsclerotia formation was reduced in the plates amended with antioxidants such as ascorbic acid, dithiothreitol (DTT), and glutathione. Surprisingly, DTT drastically scavenged H2O2, but the microsclerotia amount remained similar to the treatment of ascorbic acid and glutathione that both did not completely eliminate H2O2. This observation suggested the importance of [Formula: see text] over H2O2 in initiating microsclerotia formation. To further validate this hypothesis, the superoxide dismutase 1 (SOD1) inhibitor diethyldithiocarbamate trihydrate (DETC) and H2O2 were tested. The addition of DETC resulted in the accumulation of endogenous [Formula: see text] and more microsclerotia formation, but the treatment of H2O2 did not. The expression of SOD1 genes were also found to be upregulated in the hyphae to the microsclerotia stage, which suggested a higher endogenous [Formula: see text] stress presented in these stages. In summary, this study not only showed that the ROS stimulation remained conserved for initiating microsclerotia formation of M. phaseolina but also highlighted the importance of [Formula: see text] in initiating the hyphal differentiation to microsclerotia formation. IMPORTANCE Reactive oxygen species (ROS) have been proposed as the key stimulus for sclerotia development by studying fungal systems such as Sclerotinia sclerotiorum, and the theory has been adapted for microsclerotia development in Verticillium dahliae and Nomuraea rileyi. While many studies agreed on the association between (micro)sclerotia development and the ROS pathway, which ROS type, superoxide ([Formula: see text]) or hydrogen peroxide (H2O2), plays a major role in initiating hyphal differentiation to the (micro)sclerotia formation remains controversial, and literature supporting either [Formula: see text] or H2O2 can be found. This study confirmed the association between ROS and microsclerotia formation for the charcoal rot fungus Macrophomina phaseolina. Moreover, the accumulation of [Formula: see text] but not H2O2 was found to induce higher density of microsclerotia. By integrating transcriptomic and phenotypic assays, this study presented the first conclusive case for M. phaseolina that [Formula: see text] is the main ROS stimulus in determining the amount of microsclerotia formation.

MMP-10 from M1 macrophages promotes pulmonary vascular remodeling and pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is characterized by muscularized pulmonary blood vessels, leading to right heart hypertrophy and cardiac failure. However, state-of-the-art therapeutics fail to target the ongoing remodeling process. Here, this study shows that matrix metalloproteinases (MMP)-1 and MMP-10 levels are increased in the medial layer of vessel wall, serum, and M1-polarized macrophages from patients with PAH and the lungs of monocrotaline- and hypoxia-induced PAH rodent models. MMP-10 regulates the malignant phenotype of pulmonary artery smooth muscle cells (PASMCs). The overexpression of active MMP-10 promotes PASMC proliferation and migration via upregulation of cyclin D1 and proliferating cell nuclear antigen, suggesting that MMP-10 produced by infiltrating macrophages contributes to vascular remodeling. Furthermore, inhibition of STAT1 inhibits hypoxia-induced MMP-10 but not MMP-1 expression in M1-polarized macrophages from patients with PAH. In conclusion, circulating MMP-10 could be used as a potential targeted therapy for PAH.

Clozapine Worsens Glucose Intolerance, Nonalcoholic Fatty Liver Disease, Kidney Damage, and Retinal Injury and Increases Renal Reactive Oxygen Species Production and Chromium Loss in Obese Mice.

Clozapine is widely employed in the treatment of schizophrenia. Compared with that of atypical first-generation antipsychotics, atypical second-generation antipsychotics such as clozapine have less severe side effects and may positively affect obesity and blood glucose level. However, no systematic study of clozapine's adverse metabolic effects-such as changes in kidney and liver function, body weight, glucose and triglyceride levels, and retinopathy-was conducted. This research investigated how clozapine affects weight, the bodily distribution of chromium, liver damage, fatty liver scores, glucose homeostasis, renal impairment, and retinopathy in mice fed a high fat diet (HFD). We discovered that obese mice treated with clozapine gained more weight and had greater kidney, liver, and retroperitoneal and epididymal fat pad masses; higher daily food efficiency; higher serum or hepatic triglyceride, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and creatinine levels; and higher hepatic lipid regulation marker expression than did the HFD-fed control mice. Furthermore, the clozapine group mice exhibited insulin resistance, poorer insulin sensitivity, greater glucose intolerance, and less Akt phosphorylation; their GLUT4 expression was lower, they had renal damage, more reactive oxygen species, and IL-1 expression, and, finally, their levels of antioxidative enzymes (superoxide dismutase, glutathione peroxidase, and catalase) were lower. Moreover, clozapine reduced the thickness of retinal cell layers and increased iNOS and NF-κB expression; a net negative chromium balance occurred because more chromium was excreted through urine, and this influenced chromium mobilization, which did not help overcome the hyperglycemia. Our clozapine group had considerably higher fatty liver scores, which was supported by the findings of lowered adiponectin protein levels and increased FASN protein, PNPLA3 protein, FABP4 mRNA, and SREBP1 mRNA levels. We conclude that clozapine can worsen nonalcoholic fatty liver disease, diabetes, and kidney and retinal injury. Therefore, long-term administration of clozapine warrants higher attention.

The Ameliorative Effects of Fucoidan in Thioacetaide-Induced Liver Injury in Mice.

Liver disorders have been recognized as one major health concern. Fucoidan, a sulfated polysaccharide extracted from the brown seaweed Fucus serratus, has previously been reported as an anti-inflammatory and antioxidant. However, the discovery and validation of its hepatoprotective properties and elucidation of its mechanisms of action are still unknown. The objective of the current study was to investigate the effect and possible modes of action of a treatment of fucoidan against thioacetamide (TAA)-induced liver injury in male C57BL/6 mice by serum biochemical and histological analyses. The mouse model for liver damage was developed by the administration of TAA thrice a week for six weeks. The mice with TAA-induced liver injury were orally administered fucoidan once a day for 42 days. The treated mice showed significantly higher body weights; food intakes; hepatic antioxidative enzymes (catalase, glutathione peroxidase (GPx), and superoxide dismutase (SOD)); and a lower serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and C-reactive protein (CRP) levels. Additionally, a reduced hepatic IL-6 level and a decreased expression of inflammatory-related genes, such as cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) mRNA was observed. These results demonstrated that fucoidan had a hepatoprotective effect on liver injury through the suppression of the inflammatory responses and acting as an antioxidant. In addition, here, we validated the use of fucoidan against liver disorders with supporting molecular data.

Initial Experience With Patent Ductus Arteriosus Ligation in Pre-term Infants With Bidirectional Shunt Pattern.

Background: Patent ductus arteriosus (PDA) with a bidirectional shunt reflects critical clinical conditions. The operability of PDA with a bidirectional shunt in pre-term infants is still not clearly clarified. This study aimed to investigate the feasibility and the outcomes of PDA ligation in pre-term infants with a bidirectional shunt PDA. Methods: All pre-term infants receiving PDA ligation between 2013 and 2019 were enrolled in this prospective study. Patients were allocated into two groups based on the shunting direction of PDA, which were the left-to-right group (group A) and the bidirectional group (group B). Clinical characteristics and pre-op comorbidities were analyzed. Intraoperative complications, post-op neurological sequelae, necrotizing enterocolitis, survival, and mortality were compared between these two groups. Results: Thirty-seven pre-term infants were enrolled (18 in group A, 19 in group B). The mean post-menstrual age at PDA surgery was 32.0 ± 1.3 and 32.8 ± 1.5 weeks, respectively. Before surgery, 44.4 and 89.5% (group A vs. B) of the patients were using invasive mechanical ventilator (p < 0.01). The requirement of high-frequency oscillatory ventilatory support was significantly higher in group B. PDA rupture-related bleeding during exposing PDA or ligating PDA occurred in four infants, and all were all in group B, including one with delayed hemothorax. Early surgical mortality within 30 days of surgery was higher in group B (0 vs. 21.1%, p < 0.05), but only one death could be attributed to the surgery, which was caused by a pain-induced pulmonary hypertension crisis. The 5-year survival was 100% in group A, and 73.7% in group B (p < 0.05). Conclusion: We did not recommend routine PDA ligation in pre-term infants with a bidirectional shunt. However, a bidirectional shunt should not be an absolute contraindication if they fulfill indications of PDA closure. Unexpected intraoperative PDA rupture and delayed hemothorax in a bidirectional shunt PDA should be carefully monitored. Aggressive post-op pain control is also warranted to avoid pulmonary hypertension crisis. The post-op early mortality rate was higher in the bidirectional group, which could be inherent to their poor pre-operative lung condition. Only one death was directly related to the surgery.

Serum apoptotic marker M30 is positively correlated with early diastolic dysfunction in adolescent obesity.

PURPOSE: Obesity in adolescence has been shown to be related to cardiac geometric and functional changes. Cardiac dysfunction in adults with obesity could be attributed to chronic low-grade inflammation, apoptosis of cardiomyocyte, and glucose metabolic disorder. The aforementioned association in adolescents with obesity have never been well studied. Our aim was to determine the types of cardiac dysfunction in adolescents with obesity and survey the association between cardiac dysfunction and chronic low-grade inflammation, apoptosis, and glucose dysregulation in adolescents with obesity. METHODS: Adolescents aged between 10 and 20 years were enrolled in this study. Body mass index, waist-to-hip ratio, blood pressure, glucose metabolism, and high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-a (TNF-α), and apoptosis marker M30 levels were measured. Echocardiographic indices were also measured. The association between serum biomarkers and echocardiographic function parameters was analyzed. RESULTS: Diastolic dysfunction was the major finding in the cardiac functional assessment. The main changes in glucose metabolism were elevated C-peptide level and insulin resistance. Hs-CRP, IL-6, and M30 levels also increased with adolescent obesity. M30 was the major biomarker that was highly correlated to diastolic dysfunction indices in adolescents with obesity. CONCLUSIONS: Diastolic dysfunction was the main change in adolescent obesity. Insulin resistance, apoptotic marker M30, hs-CRP, and IL-6 were all elevated in adolescents with obesity. Only M30 was related to indices of left ventricular diastolic dysfunction among adolescents with obesity, rather than inflammation or insulin resistance.

Zoledronic acid blocks the interaction between breast cancer cells and regulatory T-cells.

BACKGROUND: Zoledronic acid (ZA), a nitrogen-containing bisphosphonate, inhibits osteoclastogenesis. Emerging evidence suggests that ZA has anti-tumor and anti-metastatic properties for breast cancer cells. In a mouse model of ZA-related osteonecrosis of the jaw, ZA administration was found to suppress regulatory T-cells (Tregs) function. Our previous reports also demonstrated ZA acted as an immune modulator to block Tregs. Manipulation of Tregs represents a new strategy for cancer treatment. However, the relationship among ZA, Tregs, and cancer cells remains unclear. In this study, we investigated the effects of ZA on the interaction of breast cancer cells and Tregs. METHODS: The anti-tumor effect of ZA on triple negative breast cancer cell lines were validated by XTT, wound healing and apoptosis analysis. A flow cytometry-based assay was used to analyze the immunosuppressive effect of Tregs treated with media conditioned by breast cancer cells, and a transwell assay was used to evaluate the chemotactic migration of Tregs. Differential gene expression profile on MDA-MB-231 treated with ZA (25 µM) was analyzed by. microarrays to describe the molecular basis of actions of ZA for possible direct anti-tumor effects. Enzyme-linked immunosorbent assays and quantitative real-time PCR were used to investigate the effect of ZA on the expression of cytokines/factors by breast cancer cells. RESULTS: ZA was found to inhibit the proliferation and migration of breast cancer cells. Media conditioned by the MDA-MB-231 cells promoted the expansion, chemotactic migration, and immunosuppressive activity of Tregs, and these effects were attenuated in a dose-dependent manner by ZA treatment, and the attenuation was due to reduced expression of selected breast cancer cell factors (CCL2, CCL5, and IDO). CONCLUSIONS: ZA can significantly affect the interaction between breast cancer cells and Tregs. Our findings indicate that ZA is a potential therapeutic agent that can be used to reduce cancer aggressiveness by abolishing the supportive role of Tregs.

Neonatal gastric perforation: a report of two cases and a systematic review.

RATIONALE: Neonatal gastric perforation is a rare and life-threatening disorder in neonates and is associated with high morbidity and mortality. However, the exact mechanisms of neonatal gastric perforation remain unknown. PATIENT CONCERNS: In this study, we reported 2 cases of neonatal gastric perforation and conducted a systematic review to analyze the prognostic factors for mortality. DIAGNOSES: Two neonates received a diagnosis of gastric perforation based on clinical presentation and imaging studies. The 2 patients underwent emergent surgery, which yielded favorable outcomes. INTERVENTIONS: We reviewed 168 cases from the literature as well as our 2 cases to analyze whether mortality in neonatal gastric perforation is associated with sex, gestational age, operation type, perforation location, or timing of perforation. OUTCOMES: The results revealed that mortality was significantly higher in preterm neonates (n = 80, P < .01) and the mortality group had a lower birth weight (n = 73, P < .05). The timing of perforation in the preterm subgroup was significantly earlier than that in the full-term subgroup (n = 90, P < .05). The outcomes about mortality of gastric perforation were significantly associated with preterm neonates (adjusted odds ratio: 4.21, 95% confidence interval: 1.28-13.88, P < .05). LESSONS: This study shows the prognostic factor of gastric perforation was significantly associated with preterm neonates. Furthermore, low-birth-weight full-term neonates had a relatively higher mortality rate than the normal-birth-weight full-term neonates. In addition, preterm neonates have an earlier timing of perforation.

Novel Ultrasonographic Fatty Liver Indicator Can Predict Hepatitis in Children With Non-alcoholic Fatty Liver Disease.

Background: Childhood non-alcoholic fatty liver disease (NAFLD) is a public health issue worldwide. To date, liver biopsy remains the gold standard for diagnosing the severity of NAFLD. However, this invasive procedure might contribute to complications. Owing to this reason, a good non-invasive tool to estimate NAFLD in children is urgently needed. We sought to investigate whether a non-invasive semi-quantitative ultrasonographic fatty liver indicator (US-FLI) can estimate NAFLD in children. Methods: Children aged between 10 and 18 years were enrolled prospectively. Abdominal ultrasonography was performed by a single experienced pediatric gastroenterologist and the non-invasive semi-quantitative US-FLI score were used. Patients were diagnosed with NAFLD if they had a US-FLI score ≥2. The anthropometric measures, obesity-related biochemical results, and levels of tumor necrosis factor-α, interleukin-6, caspase-cleaved cytokeratin fragment of cytokeratin 18 (M30), and adiponectin were also checked. Results: Overall, 117 children aged 10-18 years were enrolled. The anthropometric measures and obesity-related biochemical parameters (hsCRP, triglyceride, uric acid, AST, ALT, γ-GT, homeostatic model assessment insulin resistance (HOMA-IR), and M30) were significantly higher in the obesity group than in the non-obesity group (p < 0.05). Similarly, the US-FLI score was significantly higher in the obesity group than that in the non-obesity group (p < 0.001). Multiple linear regression showed that the US-FLI score was significantly associated with the waist-to-height ratio, uric acid, adiponectin, and M30 levels (all p < 0.05) in children with obesity. The US-FLI score ≥6 was the optimal cut-off point for predicting the hepatitis in children with NAFLD. The area under the receiver operating characteristic curve was 0.710 (95% CI: 0.572-0.847; p = 0.005). Conclusions: The non-invasive US-FLI score can predict hepatitis in children with NAFLD without mandatory liver biopsy. Moreover, the waist-to-height ratio, uric acid, adiponectin, and M30 levels were significantly associated with US-FLI score in children with obesity.

Pediatric types I and VI choledochal cysts complicated with acute pancreatitis and spontaneous perforation: A case report and literature review.

RATIONALE: Choledochal cysts are a congenital disorder of the common bile duct that can cause progressive biliary obstruction and biliary cirrhosis. They were classified by Todani into five types. Of these, type VI choledochal cysts are rarely reported in the literature. PATIENT CONCERNS: A 22-month-old girl presented with intermittent epigastralgia for approximately 10 days and fever for three days. Fasting and total parenteral nutrition were administered after admission. However, sudden onset of severe epigastric pain occurred. An abdominal sonogram showed turbid ascites and peritonitis was impressed. DIAGNOSES: An emergent exploratory laparotomy was performed, and perforation of the posterior wall of types I and VI choledochal cysts was observed. INTERVENTIONS: Intraoperative cholangiography revealed concomitant types I and VI choledochal cysts with stricture of the distal common bile duct. Definite surgery for resection of the choledochal cysts and gallbladder was performed with Roux-en-Y choledochojejunostomy. OUTCOMES: The patient had no evidence of ascending cholangitis at three years after the operation. LESSONS: Type VI choledochal cysts are rarely reported in the literature. To our knowledge, this is the first reported pediatric case of concomitant types I and VI choledochal cysts complicated with acute pancreatitis and spontaneous perforation.

Inflammatory myofibroblastic tumors of the pancreas in children: A case report and literature review.

INTRODUCTION: Inflammatory myofibroblastic tumors are an uncommon neoplasm, which are very rarely located in the pancreas. Clinically and radiologically, this rare pancreatic tumor presents as an abdominal mass lesion that mimics other pancreatic tumors, and should therefore be considered in the differential diagnosis of pancreatic tumors. CLINICAL FINDINGS AND DIAGNOSIS: The 15-year-old boy complained of abdominal pain over the left upper quadrant with intermittent fever for 7 days. Abdominal sonography revealed one cystic lesion with a hyperechoic component in the left upper quadrant of the abdomen. Surgical excision was performed and postoperative findings indicated a pancreatic tail tumor. The pathology indicated inflammatory myofibroblastic tumors. To our knowledge, this patient is a unique case as the tumor was located in the pancreatic tail only, sparing the body. INTERVENTIONS AND OUTCOMES: The patient underwent tumor resection and segmental resection of the transverse colon with simple closure. The patient had no evidence of disease recurrence at 3 years follow-up. CONCLUSION: Inflammatory myofibroblastic tumors of the pancreas in children are extremely rare. Surgical excision is the standard treatment, and corticosteroids use in children need more large-scale studies.

Therapeutic potential of pro-angiogenic BPC157 is associated with VEGFR2 activation and up-regulation.

BPC 157, a pentadecapeptide with extensive healing effects, has recently been suggested to contribute to angiogenesis. However, the underlying mechanism is not yet clear. The present study aimed to explore the potential therapeutic effect and pro-angiogenic mechanism of BPC 157. As demonstrated by the chick chorioallantoic membrane (CAM) assay and endothelial tube formation assay, BPC 157 could increase the vessel density both in vivo and in vitro, respectively. BPC 157 could also accelerate the recovery of blood flow in the ischemic muscle of the rat hind limb as detected by laser Doppler scanning, indicating the promotion of angiogenesis. Histological analysis of the hind limb muscle confirmed the increased number of vessels and the enhanced vascular expression of vascular endothelial growth factor receptor 2 (VEGFR2) in rat with BPC 157 treatment. In vitro study using human vascular endothelial cells further confirmed the increased mRNA and protein expressions of VEGFR2 but not VEGF-A by BPC 157. In addition, BPC 157 could promote VEGFR2 internalization in vascular endothelial cells which was blocked in the presence of dynasore, an inhibitor of endocytosis. BPC 157 time dependently activated the VEGFR2-Akt-eNOS signaling pathway which could also be suppressed by dynasore. The increase of endothelial tube formation induced by BPC 157 was also inhibited by dynasore. This study demonstrates the pro-angiogenic effects of BPC 157 that is associated with the increased expression, internalization of VEGFR2, and the activation of VEGFR2-Akt-eNOS signaling pathway. BPC 157 promotes angiogenesis in CAM assay and tube formation assay. BPC 157 accelerates the blood flow recovery and vessel number in rats with hind limb ischemia. BPC 157 up-regulates VEGFR2 expression in rats with hind limb ischemia and endothelial cell culture. BPC 157 promotes VEGFR2 internalization in association with VEGFR2-Akt-eNOS activation. KEY MESSAGE: BPC 157 promotes angiogenesis in CAM assay and tube formation assay. BPC 157 accelerates the blood flow recovery and vessel number in rats with hind limb ischemia. BPC 157 up-regulates VEGFR2 expression in rats with hind limb ischemia and endothelial cell culture. BPC 157 promotes VEGFR2 internalization in association with VEGFR2-Akt-eNOS activation.