The novel roles of YULINK in the migration, proliferation and glycolysis of pulmonary arterial smooth muscle cells: implications for pulmonary arterial hypertension.

BACKGROUND: Abnormal remodeling of the pulmonary vasculature, characterized by the proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) along with dysregulated glycolysis, is a pathognomonic feature of pulmonary arterial hypertension (PAH). YULINK (MIOS, Entrez Gene: 54468), a newly identified gene, has been recently shown to possess pleiotropic physiologic functions. This study aims to determine novel roles of YULINK in the regulation of PAH-related pathogenesis, including PASMC migration, proliferation and glycolysis. RESULTS: Our results utilized two PAH-related cell models: PASMCs treated with platelet-derived growth factor (PDGF) and PASMCs harvested from monocrotaline (MCT)-induced PAH rats (PAH-PASMCs). YULINK modulation, either by knockdown or overexpression, was found to influence PASMC migration and proliferation in both models. Additionally, YULINK was implicated in glycolytic processes, impacting glucose uptake, glucose transporter 1 (GLUT1) expression, hexokinase II (HK-2) expression, and pyruvate production in PASMCs. Notably, YULINK and GLUT1 were observed to colocalize on PASMC membranes under PAH-related pathogenic conditions. Indeed, increased YULINK expression was also detected in the pulmonary artery of human PAH specimen. Furthermore, YULINK inhibition led to the suppression of platelet-derived growth factor receptor (PDGFR) and the phosphorylation of focal adhesion kinase (FAK), phosphoinositide 3-kinase (PI3K), and protein kinase B (AKT) in both cell models. These findings suggest that the effects of YULINK are potentially mediated through the PI3K-AKT signaling pathway. CONCLUSIONS: Our findings indicate that YULINK appears to play a crucial role in the migration, proliferation, and glycolysis in PASMCs and therefore positioning it as a novel promising therapeutic target for PAH.

Unnecessary radiation exposure during diagnostic radiography in infants in a neonatal intensive care unit: a retrospective cohort study.

Unnecessary radiation exposure (URE) during radiographic examination is an issue among infants in neonatal intensive care units (NICUs). The causes of URE have not been fully explored. This study investigated the incidence and identified the causes of URE in infants during diagnostic radiography in a NICU. This was a retrospective cohort study. We retrieved and analysed requests and radiographs taken at a tertiary NICU between September and November 2018. URE was defined as the rate of discordance between requests and images taken (DisBRI) and unnecessary radiation exposure in irrelevant regions (UREIR) during radiography. We compared the rates of URE between very low-birth-weight (VLBW, birth weight < 1500 g) infants and non-VLBW infants. A total of 306 radiographs from 88 infants were taken. The means ± standard deviations (SDs) of gestational age and birth weight were 35.7 ± 3.6 weeks and 2471 ± 816 g, respectively. Each infant underwent an average of 3.5 radiographs. The DisBRI rate was 1.3% and was mostly related to poor adherence to requests. The UREIR rates in thoraco-abdominal babygrams were 89.6% for the head, 14.8% for the elbows and 18.4% for the knee and were mainly related to improper positioning of and collimation in infants while performing radiography. The UREIR rates for the head, knee and ankle were higher in VLBW infants than in non-VLBW infants (94.6% vs. 85.6%, 27.0% vs. 11.5% and 5.4% vs. 0.7%, respectively, p < 0.05). CONCLUSIONS: URE during diagnostic radiography is common in sick infants and is mainly related to improper positioning and collimation during examinations. Adherence to protocols when performing radiographic examination or using ultrasonography may be a solution to reduce URE in infants in NICUs. WHAT IS KNOWN: • The risk of unnecessary radiation exposure (URE) during radiography has been a common and important issue in sick infants in neonatal intensive care units (NICUs). • The new point-of-care ultrasound (POCUS) technique decreases the need for chest films and prevents radiation exposure in neonates. WHAT IS NEW: • In the NICU, URE is still a common issue in critically ill infants during radiographic examinations. The causes of URE during diagnostic radiography are mainly due to improper positioning and collimation during examinations. • The incidence of URE in irrelevant regions is higher in very low-birth-weight (VLBW) infants than in non-VLBW infants.

Chronic Nocturnal Abdominal Pain as the Presentation of Inverted Meckel Diverticulum: A Case Report.

The common clinical manifestations of Meckel's diverticulum include painless lower gastrointestinal bleeding and intestinal obstruction due to intussusception. Intussusception induced by inverted Meckel's diverticulum has rarely been reported; furthermore, there is no report thus far of chronic nocturnal abdominal pain as a presenting symptom in children with Meckel's diverticulum. A 4-year-and-10-month-old girl with no significant history of previous illness presented with the sole complaint of chronic nocturnal abdominal pain for 3 months. The patient was reported to be asymptomatic during the day. A provisional diagnosis of chronic ileoileal intussusception was already under consideration in her previous hospital visits elsewhere. Physical examination revealed a soft, non-distended abdomen without tenderness. Imaging studies revealed ileoileal intussusception. Exploratory laparotomy showed ileoileal intussusception induced by an inverted Meckel's diverticulum with ulceration. The patient underwent successful surgery and made a full recovery. We report this case to remind physicians that Meckel's diverticulum should be considered in differential diagnosis of children presenting with the isolated symptom of chronic nocturnal abdominal pain.

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.

Mechanism of resveratrol-induced relaxation of the guinea pig fundus.

BACKGROUND: Resveratrol is a polyphenolic compound that can be isolated from plants and also is a constituent of red wine. Resveratrol induces relaxation of vascular smooth muscle and may prevent cardiovascular diseases. PURPOSE: Impaired gastric accommodation plays an important role in functional dyspepsia and fundic relaxation and is a therapeutic target of functional dyspepsia. Although drugs for fundic relaxation have been developed, these types of drugs are still rare. The purpose of this study was to investigate the relaxant effects of resveratrol in the guinea pig fundus. STUDY DESIGN: We studied the relaxant effects of resveratrol in the guinea pig fundus. In addition, we investigated the mechanism of resveratrol-induced relaxation on the guinea pig fundus by using tetraethylammonium (a non-selective potassium channel blocker), apamine (a selective inhibitor of the small conductance calcium-activated potassium channel), iberiotoxin (an inhibitor of large conductance calcium-activated potassium channels), glibenclamide (an ATP-sensitive potassium channel blocker), KT 5720 (a cAMP-dependent protein kinase A inhibitor), KT 5823 (a cGMP-dependent protein kinase G inhibitor), NG-nitro-L-arginine (a competitive inhibitor of nitric oxide synthase), tetrodotoxin (a selective neuronal Na+ channel blocker), ω-conotoxin GVIA (a selective neuronal Ca2+ channel blocker) and G-15 (a G-protein coupled estrogen receptor antagonist). RESULTS: The results of this study showed that resveratrol has potent and dose-dependent relaxant effects on the guinea pig fundic muscle. In addition, the results showed that resveratrol-induced relaxation of the guinea pig fundus occurs through nitric oxide and ATP-sensitive potassium channels. CONCLUSION: This study provides the first evidence concerning the relaxant effects of resveratrol in the guinea pig fundic muscle strips. Furthermore, resveratrol may be a potential drug to relieve gastrointestinal dyspepsia.

Estradiol mediates relaxation of porcine lower esophageal sphincter.

Most pregnant women have symptoms of gastroesophageal reflux disease (GERD) during pregnancy. Postmenopausal hormone replacement therapy is associated with GERD. The effects of estradiol on lower esophageal sphincter (LES) motility and GERD are not clearly known. The purpose of this study is to investigate the effects of estradiol on the motility of the porcine LES. Relaxations of clasp and sling strips of porcine LES caused by estradiol were measured using isometric transducers. We investigated the mechanism of estradiol-induced relaxation of the porcine LES using tetraethylammonium, apamine, iberiotoxin, glibenclamide, KT5720, KT5823, NG-nitro-l-arginine, tetrodotoxin, and ω-conotoxin GVIA. Reverse transcription polymerase chain reaction (PCR) analysis and immunohistochemistry (IHC) were performed to determine the existence of the G protein-coupled estrogen receptor (GPER) in the porcine LES. In endothelin-1-precontracted porcine LES strips, estradiol caused marked relaxations in a concentration-dependent manner. The mechanism of estradiol-induced relaxation on the porcine LES was associated with the potassium channel. Reverse transcription PCR analysis and IHC revealed that GPER was expressed in the sling and clasp fibers of the porcine LES. This finding suggests that GPER mediates the relaxation of the porcine LES. Estradiol may play a role in LES motility.

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.

Granulocyte Colony-Stimulating Factor Alleviates Bacterial-Induced Neuronal Apoptotic Damage in the Neonatal Rat Brain through Epigenetic Histone Modification.

Bacterial meningitis during the perinatal period may cause long-term neurological deficits. The study investigated whether bacterial lipopolysaccharide (LPS) derived from E. coli. led to neuronal apoptosis with an impaired performance of long-term cognitive function involving the activation of histone modification in the TNF-α gene promoter. Further, we looked into the therapeutic efficacy of granulocyte colony-stimulating factor (G-CSF) in a neonatal brain suffering from perinatal bacterial meningitis. We applied the following research techniques: neurobehavioral tasks, confocal laser microscopy, chromatin immunoprecipitation, and Western blotting. At postnatal day 10, the animals were subjected to LPS and/or G-CSF. The target brain tissues were then collected at P17. Some animals (P45) were studied using neurobehavioral tasks. The LPS-injected group revealed significantly increased expression of NF-κB phosphorylation and trimethylated H3K4 in the TNFA gene promoter locus. Furthermore, the caspase-3, neuronal apoptosis expression, and an impaired performance in cognitive functions were also found in our study. Such deleterious outcomes described above were markedly alleviated by G-CSF therapy. This study suggests that selective therapeutic action sites of G-CSF through epigenetic regulation in the TNFA gene promoter locus may exert a potentially beneficial role for the neonatal brain suffering from perinatal bacterial-induced meningitis.

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.

Nonobstructive dilation of urinary tract and later development of obstruction: report of one case.

Cases of nonobstructive dilation of the upper urinary tract subsequently becoming obstructive are rare. We report a case involving a male child approximately 2.5 years old (29 months) who presented with an obstruction of the ureterovesical junction, which had been diagnosed and treated for nonobstructive dilation at another hospital 15 months earlier. At our hospital, we found no ureteral orifice by cystoscopic examination. Exploratory surgery was performed and complete obstruction of the ureterovesical junction was observed. We resected the segment involved in the obstruction and performed an ureteroneocystostomy. Patients found to have nonobstructive dilation of the urinary tract, a common and often innocuous finding, need careful follow-up to ensure that obstructions that may develop later can be treated in a timely manner.

Biopsy proven acute tubular necrosis associated with vancomycin in a child: case report and literature review.

Vancomycin-related nephrotoxicity typically manifests as acute tubulointerstitial nephritis. The drug does appear, however, to increase the nephrotoxicity of concurrently administered aminoglycosides. The extent of direct tubular toxicity attributable to vancomycin, especially in the absence of aminoglycoside treatment, does not appear to have been previously described. We report a case of biopsy-proven acute tubular necrosis secondary to vancomycin toxicity in a 13-year-old boy where there was no likely alternate explanation for toxic or ischemic injury. No hemodialysis was required, and the patient made a full recovery with subsequently regained renal function.

De novo urothelial carcinoma in a pediatric recipient of living donor kidney graft.

De novo urothelial carcinoma is relatively rare among post-transplant malignancies and never reported in pediatric kidney transplant recipients. In this paper, we reported one 12-yr-old male case with painless gross hematuria as the initial manifestation of de novo urothelial carcinoma in living donor graft pelvis. We emphasize the importance that cystoscopy and retrograde pyelography of native and transplant kidneys should be performed in all kidney transplant recipients with painless gross hematuria.

Imaging findings in fibroepithelial polyps causing ureteropelvic junction obstruction: report of one case.

Fibroepithelial polyps causing ureteropelvic junction obstruction are rarely reported in the pediatric age group. We report a 9-year-old boy who had ureteropelvic junction obstruction that proved to be owing to benign fibroepithelial polyps. Intravenous pyelography showed hydronephrosis with filling defects at the left ureteropelvic junction. Operative exploration revealed several finger-like polypoid neoplasms obstructing the lumen. The involved segment was resected and a dismembered pyeloplasty was performed. Fibroepithelial polyps were diagnosed by histology. The clinical imaging findings, features and methods of surgical treatment of this rare lesion are discussed.