Accurate intraoperative tissue identification is critical to tumor surgery. However, conventional methods are labor‐ and time‐intensive, which greatly delay the intraoperative decision‐making. Herein, a matrix metalloproteinase (MMP)14‐activated NIR‐II nanoprobe (A&MMP@Ag2S‐AF7P) is presented for rapid unperturbed‐tissue analysis for ex vivo and in vivo neuroblastoma diagnosis. A&MMP@Ag2S‐AF7P displays negligible fluorescence in normal tissues but is activated quickly by inhibiting the fluorescence resonance energy transfer (FRET) between Ag2S QDs and A1094 mediated by MMP14 overexpressed in neuroblastoma; meanwhile, the exposure of the membrane penetrating peptide R9 (TAT‐peptide) results in efficient internalization of nanoprobes in the cancer cells, providing superior tumor‐to‐normal (T/N) tissue ratio. Instant illumination of the lesion and well‐defined tumor margins make the nanoprobes a suitable rapid diagnostic reagent for cancer surgical or tissue biopsy procedures.
Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. MethodsWe did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. FindingsWe included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58•0%) were male. Median gestational age at birth was 38 weeks (IQR 36-39) and median bodyweight at presentation was 2•8 kg (2•3-3•3). Mortality among all patients was 37 (39•8%) of 93 in low-income countries, 583 (20•4%) of 2860 in middle-income countries, and 50 (5•6%) of 896 in high-income countries (p<0•0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90•0%] of ten in lowincome countries, 97 [31•9%] of 304 in middle-income countries, and two [1•4%] of 139 in high-income countries; p≤0•0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2•78 [95% CI 1•88-4•11], p<0•0001; middle-income vs high-income countries, 2•11 [1•59-2•79], p<0•0001), sepsis at presentation (1•20 [1•04-1•40], p=0•016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4-5 vs ASA 1-2, 1•82 [1•40-2•35], p<0•0001; ASA 3 vs ASA 1-2, 1•58, [1•30-1•92], p<0•0001]), surgical safety checklist not used (1•39 [1•02-1•90], p=0•035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1•96, [1•4...
Background Pancreaticobiliary maljunction (PBM) is often associated with congenital choledochal cyst, protein plugs and pancreatitis. Early diagnosis and timely treatment largely depend on imaging. We assessed a series of PBM in children, comparing imaging procedure with histological and pathological findings with regard to diagnosis. Methods A retrospective analysis was conducted in 75 pediatric patients with PBM. PBM was defined as common channel at[5 mm. Two radiologists assess the shape of the bile duct and gallbladder, pancreatitis, surgical pathology, symptom profiles, operative notes and pathological records were compared with the imaging findings. Results Dilatation of the bile duct was detected in 45 subjects out of the 46 subjects who underwent computed tomography (CT) and nine was diagnosis as PBM. Forty out of 41 subjects were revealed bile duct dilatation in ultrasonography (US). Bile duct dilatation was seen in 59 out of 60 subjects receiving magnetic resonance cholangiopancreatography (MRCP) and 39 were diagnosed as PBM. Seventy-four out of 75 subjects successfully underwent intraoperative cholangiography (IOC); a diagnosis of PBM was established in 60 cases based on IOC alone. The diagnosis rate of pediatric PBM varied significantly among the four groups (P \ 0.0001). Pair-wise comparison showed a significant difference between the groups of MRCP and CT (P \ 0.0001), MRCP and US (P \ 0.0001), IOC and CT (P \ 0.0001), IOC and US (P \ 0.0001), CT and US (P = 0.0027), and there is no significant difference between the groups of IOC and MRCP (P = 0.0502). Conclusion US, IOC, CT and MRCP are valuable in showing dilatation of the bile duct and complications in pediatric PBM. MRCP is non-invasive, gives clear views of the pancreaticobiliary junction and should be the first choice for the diagnosis of PBM in children.
Objective The umbilical cord provides nutrition and oxygen to the fetus. The aim of this study was to determine the effects of acetylcholine (ACh) on umbilical cords from humans and other mammals, and the mechanisms of ACh-mediated vasoconstriction in the human umbilical cord.Design Human and animal umbilical cords used in vascular and cellular experiments.Setting Institute for Fetology, First Hospital of Soochow University, Suzhou, China.Population A total of 85 pregnant women, 16 Sprague Dawley rats and seven pregnant sheep.Methods Umbilical cord veins and arteries from humans, rats and sheep, aortas and mesenteric arteries from rats, and mesenteric, carotid and femoral arteries from ovine fetuses were used to compare vascular functions in response to ACh and to determine the mechanisms of ACh-mediated umbilical vasoconstriction. Vascular tension and ion channel currents were measured on isolated vessels and smooth muscle cells from human umbilical cords.Main outcome measures Provision of new evidence to conclude that ACh-stimulated vasoconstriction is common to all umbilical cords, and cellular mechanisms are linked to potassium channels.Results ACh caused reliable vasoconstriction in umbilical veins/ arteries in humans, rats and sheep, but not in any other vessels, including fetal vessels. Atropine inhibited the effects of ACh. The mRNA of ACh-muscarinic receptor subtypes M 1 -M 5 was expressed in human umbilical vessels. The protein kinase C antagonist GF109203X and the calcium inhibitor nifedipine decreased ACh-induced vasoconstriction in human umbilical vessels. ACh also caused a reduction in whole-cell potassium channel currents and the single-channel current of largeconductance calcium-activated potassium (BKca) channels.Conclusion Umbilical vessels are significantly different from other vessels in their response to ACh. BKca channels in smooth muscle cells may play important roles in ACh-mediated vasoconstriction in human umbilical cords. This information may be important for fetal medicine and practice with regard to the effect on fetal development of umbilical vascular functions.Keywords Acetylcholine, BKca current, muscarinic receptor, umbilical cord vessels, vascular constriction.
BackgroundThe aim of this study was to assess factors for delineating the pancreaticobiliary junction in the presence of pediatric congenital choledochal cysts (CCC) using Magnetic resonance cholangiopancreatography (MRCP).MethodsRetrospective review of medical records for 48 patients with CCC was conducted, including demographics, biliary amylase and MRCP findings if available. With univariate and multivariate logistic regression, we measured significant factors affecting pancreaticobiliary maljunction(PBM) diagnoses by MRCP.ResultsOf the subjects enrolled with CCC. Twenty-eight cases had PBM according to MRCP. Univariate analysis confirmed that age, cyst diameter > 30 mm and cysts that descended to the introitus pelvis affected junctional delineation and detection of PBM (P<0.05). Stepwise logistic regression analysis confirmed large cysts in the introitus pelvis predicted pancreaticobiliary junctional delineation in MRCP and these data agreed with the literature. A correlation between cyst diameter and the length of the common channel was found as was cyst diameter and biliary amylase although there were no significant differences between them.ConclusionsAge, cyst diameter >30 mm and descending cysts into the introitus pelvis affected junctional delineation of the pancreatic and bile duct in PBM with MRCP. Large cyst descension into the introitus pelvis was an independent factors affecting PBM detection.
Pancreaticobiliary maljunction (PBM) is associated with high risk of epithelial atypical growth and malignant transformation of the bile duct or gallbladder. However, overall changes in genetic expression have not been examined in children with PBM. Genome-wide expression was analyzed using peripheral blood samples from 10 children with PBM and 15 pediatric controls. Differentially expressed genes (DEGs) were identified using microarray. Bioinformatics analysis was conducted using Gene Ontology and KEGG analyses. The top 5 in the up-regulated genes in PBM were verified with qRT-PCR. Receiver operator characteristic curve analysis was conducted to evaluate the predictive accuracy of selected genes for PBM. The microarray experiments identified a total of 876 DEGs in PBM, among which 530 were up-regulated and the remaining 346 were down-regulated. Verification of the top 5 up-regulated genes ( TYMS , MYBPC1 , FUT1 , XAGE2 , and GREB1L ) by qRT-PCR confirmed the up-regulation of MYBPC1 and FUT1 . Receiver operating characteristic curve analysis suggested that FUT1 and MYBPC1 up-regulation could be used to predict PBM, with the area under the curve of 0.873 (95%CI=0.735−1.000) and 0.960 (95%CI=0.891−1.000), respectively. FUT1 and MYBPC1 were up-regulated in children with PBM, and could be used as potential biomarkers for PBM.
ObjectiveThe aims of this study were to highlight some epidemiological aspects of intussusception cases younger than 48 months and to develop a forecasting model for the occurrence of intussusception in children younger than 48 months in Suzhou.DesignA retrospective study of intussusception cases that occurred between January 2007 and December 2017.SettingRetrospective chart reviews of intussusception paediatric patients in a large Children’s hospital in South-East China were performed.ParticipantsThe hospital records of 13 887 intussusception cases in patients younger than 48 months were included in this study.InterventionsThe modelling process was conducted using the appropriate module in SPSS V.23.0.MethodsThe Box-Jenkins approach was used to fit a seasonal autoregressive integrated moving average (ARIMA) model to the monthly recorded intussusception cases in patients younger than 48 months in Suzhou from 2007 to 2016.ResultsEpidemiological analysis revealed that intussusception younger than 48 months was reported continuously throughout the year, with peaks in the late spring and early summer months. The most affected age group was younger than 36 months. The time-series analysis showed that an ARIMA (1,0,1 1,1,1)12 model offered the best fit for surveillance data of intussusception younger than 48 months. This model was used to predict intussusception younger than 48 months for the year 2017, and the fitted data showed considerable agreement with the actual data.ConclusionARIMA models are useful for monitoring intussusception in patients younger than 48 months and provide an estimate of the variability to be expected in future cases in Suzhou. The models are helpful for predicting intussusception cases in Suzhou and could be useful for developing early warning systems. They may also play a key role in early detection, timely treatment and prevention of serious complications in cases of intussusception.
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