Executive function elevated by long term high-intensity physical activity and the regulation role of beta-band activity in human frontal region.

The importance of physical activity (PA) to people's health has become a consensus around the world, and regular long-term PA has been accepted as an alternative preventive measure for many chronic medical conditions. Although the daily PA have several benefits for the public, the systematic research on its effect in human physiology, cognition and cerebral nerve level is not fully studied. Hence, in this study, we aim to investigate this question in several specific aspects: basal heart rate, executive function, and neural oscillatory activity in the brain. A total of 146 subjects participated in this study and they were divided into two groups. One group (SG) is the long-term training (more than 8 years) subjects in soccer (n = 31), and the other group (CG) is a normal control group (n = 115). The heart rate was monitored with a portable equipment. Besides, 24 subjects (14 in SG and 10 in CG) participated the Go/No-Go task and EEG recording before and after exercise fatigue task. In the physiology level, we found that in the non-training time, the heart rate in CG group is significantly higher than that of the SG group (P < 0.001). In the cognition level, we found that the SG group has a faster reaction time that that of CG group (P < 0.01), while for the accuracy, two groups did show significant difference. In the neural level in the brain, we found a significant abnormal increased beta-band (around 25 Hz) activity in CG group after the exercise fatigue task immediately. Long-term high-intensity physical activity reduces basal heart rate, improves executive function, and improve the central tolerance of the body under the stimulation of fatigue and stress. These benefits of long-term activity could be used as a manual to guide people's healthy life.

Modified lung ultrasound score for bronchopulmonary dysplasia predicts late respiratory outcomes in preterm infants.

OBJECTIVE: Lung ultrasound (LUS) is a useful and radiation-free diagnostic tool for predicting bronchopulmonary dysplasia, which is a risk factor for late respiratory disease. However, data on the relationship of LUS with late respiratory disease was scarce. This study aims to determine whether LUS is associated with late respiratory disease during early childhood. METHODS: This prospective cohort study enrolled preterm infants born before 32 weeks of gestation. LUS was performed at 36 weeks' postmenstrual age. The predictive values of a modified lung ultrasound (mLUS) score based on eight standard sections were assessed to predict late respiratory disease, defined as a physician diagnosis of bronchopulmonary dysplasia deterioration, asthma, reactive airway disease, bronchiolitis, pneumonia, or respiratory-related hospitalization during the first 2 years of life. RESULTS: A total of 94 infants completed follow-up, of whom 74.5% met the late respiratory disease criteria. The mLUS scores were significantly associated with late respiratory disease (adjusted odds ratio: 1.23, CI: 1.10-1.38, p < 0.001). The mLUS scores also well predicted late respiratory disease (AUC = 0.820, 95% CI: 0.733-0.907). These scores were superior to the classic lung ultrasound score (p = 0.02) and as accurate as the modified NICHD-defined bronchopulmonary dysplasia classification (p = 0.91). A mLUS score ≥14 was the optimal cutoff point for predicting late respiratory disease. CONCLUSION: The modified lung ultrasound score correlates significantly with late respiratory disease and well predicts it in preterm infants during the first 2 years of life.

Analysis of the operational status of the three-level referral system for urologic ultrasound screening and risk factors for renal pelvic dilatation in high-risk children.

Background: Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) are the primary cause of end-stage renal disease in children, early diagnosis and treatment can significantly improve the kidney function. Among CAKUT, renal pelvis dilatation (RPD) due to various causes has the highest detection rate, which can be detected early by postnatal ultrasound screening. Since 2010, the Children's Hospital of Fudan University (CHFU), together with the Minhang District Maternal and Child Health Hospital (MCH) and Community Health Centres (CHCs) of Minhang District has created a three-level referral system for urological ultrasound screening. This study aims to describe the operation of a three-level referral system for ultrasound screening of CAKUT and to select risk factors of RPD in high-risk children. Methods: The operation of the three-level referral system was assessed by analyzing the screening volume, screening rate, referral rate, and follow-up rate; risk factors of RPD in high-risk children were selected by chi-square test and multivariate logistic regression. Results: A total of 16,468 high-risk children were screened in ten years, and the screening volume was maintained at about 1,500 cases per year; the screening rate showed a linear increase, from 36.8% in 2010 to 98.2% in 2019; the referral rate from the CHCs to the MCH was 89.9% significantly higher after 2015 than that of 84.7% from 2010 to 2015; the follow-up rate after 2015 was 71.0% significantly higher than that of 46.3% from 2010 to 2015. Multivariate logistic regression analysis showed that the risk of RPD was 1.966 times higher in males than in females, and the risk of moderate to severe RPD was 2.570 times higher in males than in females; the risk of RPD in preterm children was 1.228 times higher than that of full-term children; and the risk of RPD was 1.218 times higher in twins than in singles. Conclusions: The screening volume of the three-level referral system has remained stable over a decade, with significantly higher screening, referral, and follow-up rates. Males, preterm, and twins are risk factors of RPD in high-risk children; males are also risk factors for moderate to severe RPD in high-risk children.

The characteristics of daily exercise load of students of different grades in a primary school in Beijing / 中国学校卫生

Objective@#To analyze the characteristics of the daily exercise load and the One Hour of Moderate to Vigorous Physical Activity (MVPA) per day among primary school students, so as to provide a reference for improving the quality of the physical activity of primary school students in school.@*Methods@#A total of 223 students from an elementary school in Beijing from May to June of 2023, were selected by stratified random cluster sampling method. The Polar Verity Sense heart rate arm band was used to monitor and evaluate the daily exercise load heart rate according to different grades, gender and physical quality.@*Results@#The average heart rate of primary school students in outdoor class, zero point sports, recess and indoor class was (130.01±13.11, 119.89± 16.02,109.96±8.11,96.81±7.89) times/min, respectively, and only 4.04% students met the standard of 1 hour MVPA daily. From the perspective of different grades, the MVPA time ratio of lower grade students in outdoor class, zero point sports and big break was 28.41%, 42.47% and 8.24%, that of middle grade students was 18.33%, 6.41% and 5.90%, and that of senior students was 45.91%, 3.88% and 11.43%. The number of students who achieved 1 hour daily MVPA was 5.41%, 0 and 6.67%. Time ratio of MVPA in outdoor classes, zero hour sports and big breaks accounted for 30.09%, 16.34% and 9.23% for boys, 31.70%, 16.24 % and 6.13% for girls, and the interval distribution of boys and girls who achieved MVPA for one hour per day was 5.88% and 2.86%.Time ratio of MVPA for students with excellent physical fitness were 33.19%, 21.76% and 8.25% in outdoor class, zero point sports and big break, while those with good physical fitness were 29.76%, 12.93% and 8.19%.A total of 21.78%, 5.99% and 4.80% of the students passed the physical fitness test, and the number of students with excellent, good and passed the physical fitness test who achieved the daily 1 hour MVPA was 5.88%, 3.77% and 0.@*Conclusion@#In the present study, elementary and middle school students time for in school physical activity was adequate, but there are problems of low loading intensity and insufficient time for MVPA. It is necessary to arrange targeted physical activity programs for students of different grades, genders and physical fitness levels to increase the daily exercise load of students in school.

Artificial tumor microenvironment regulated by first hemorrhage for enhanced tumor targeting and then occlusion for synergistic bioactivation of hypoxia-sensitive platesomes.

The unique characteristics of the tumor microenvironment (TME) could be exploited to develop antitumor nanomedicine strategies. However, in many cases, the actual therapeutic effect is far from reaching our expectations due to the notable tumor heterogeneity. Given the amplified characteristics of TME regulated by vascular disrupting agents (VDAs), nanomedicines may achieve unexpected improved efficacy. Herein, we fabricate platelet membrane-fusogenic liposomes (PML/DP&PPa), namely "platesomes", which actively load the hypoxia-activated pro-prodrug DMG-PR104A (DP) and physically encapsulate the photosensitizer pyropheophorbide a (PPa). Considering the different stages of tumor vascular collapse and shutdown induced by a VDA combretastatin-A4 phosphate (CA4P), PML/DP&PPa is injected 3 h after intraperitoneal administration of CA4P. First, CA4P-mediated tumor hemorrhage amplifies the enhanced permeation and retention (EPR) effect, and the platesome-biological targeting further promotes the tumor accumulation of PML/DP&PPa. Besides, CA4P-induced vascular occlusion inhibits oxygen supply, followed by photodynamic therapy-caused acute tumor hypoxia. This prolonged extreme hypoxia contributes to the complete activation of DP and then high inhibitory effect on tumor growth and metastasis. Thus, such a combining strategy of artificially-regulated TME and bio-inspired platesomes pronouncedly improves tumor drug delivery and boosts tumor hypoxia-selective activation, and provides a preferable solution to high-efficiency cancer therapy.

Comparison of percutaneous permeation profiles of flurbiprofen enantiomers.

Flurbiprofen is clinically effective for the treatment of acute or long-term rheumatoid arthritis and osteoarthritis. Studies showed that S-flurbiprofen had better anti-inflammatory effect than R-flurbiprofen. As flurbiprofen racemates are usually used in the form of transdermal preparations, such as Flurbiprofen Cataplasms (Zepolas), it is of great significance to investigate the percutaneous permeation profiles of flurbiprofen enantiomers for considering whether it is necessary to develop the transdermal preparation with single optical enantiomer. Taking the economy into consideration, the flurbiprofen enantiomers as the mode drug and the CHIRALPAKAAGP column we had as instrument were used to perform the following experiments. On the basis of experiences provided by predecessors, we made some improvements to the analytical conditions, and method validation was developed to verify the feasibility of the method. The results showed that the established method could be used to analyze the percutaneous permeation profiles of flurbiprofen enantiomers in the flurbiprofen cataplasms accurately and effectively, and the percutaneous permeation profiles of flurbiprofen enantiomers had no significantly difference no matter under what conditions (P > 0.05).

A modified lung ultrasound score to evaluate short-term clinical outcomes of bronchopulmonary dysplasia.

BACKGROUND: Lung ultrasound (LUS) is a useful tool for assessing the severity of lung disease, without radiation exposure. However, there is little data on the practicality of LUS in assessing the severity of bronchopulmonary dysplasia (BPD) and evaluating short-term clinical outcomes. We adapted a LUS score to evaluate BPD severity and assess the reliability of mLUS score correlated with short-term clinical outcomes. METHODS: Prospective diagnostic accuracy study was designed to enroll preterm infants with gestational age < 34 weeks. Lung ultrasonography was performed at 36 weeks postmenstrual age. The diagnostic and predictive values of new modified lung ultrasound (mLUS) scores based on eight standard sections were compared with classic lung ultrasound (cLUS) scores. RESULTS: A total of 128 infants were enrolled in this cohort, including 30 without BPD; 31 with mild BPD; 23 with moderate BPD and 44 with severe BPD. The mLUS score was significantly correlated with the short-term clinical outcomes, superior to cLUS score. The mLUS score well correlated with moderate and severe BPD (AUC = 0.813, 95% CI 0.739-0.888) and severe BPD (AUC = 0.801, 95% CI 0.728-0.875), which were superior to cLUS score. The ROC analysis of mLUS score to evaluate the other short-term outcomes also showed significant superiority to cLUS score. The optimal cutoff points for mLUS score were 14 for moderate and severe BPD and 16 for severe BPD. CONCLUSIONS: The mLUS score correlates significantly with short-term clinical outcomes and well evaluates these outcomes in preterm infants.

Investigation on the hesitancy of COVID-19 vaccination among liver transplant recipients: A cross-sectional study in China.

Objectives: The hospitalization and mortality rate from COVID-19 appears to be higher in liver transplant recipients when compared with general populations. Vaccination is an effective strategy to reduce the risk during the COVID-19 pandemic. We aimed to evaluate COVID-19 vaccine hesitancy in liver transplant recipients. Methods: In April 2022, we conducted an online-based survey through WeChat platform to investigate the vaccination hesitancy among liver transplant recipients followed at Shanghai Renji Hospital and further explore possible influencing factors. Survey items included multiple choice, Likert-type rating scale and open-ended answers. Participants were classified as no hesitancy group and hesitancy group. Using univariate analysis, ROC curve analysis and multiple logistic regression to evaluate associations between baseline characteristics and COVID-19 vaccine hesitancy. Results: 449 liver transplant recipients participated in the survey with 299 (66.6%) of them being categorized as vaccine hesitancy. In no hesitancy group, 73 (48.7%) recipients had completed vaccination, while 77 (51.3%) were not yet but intended to be vaccinated. In contrast, 195 (65.2%) recipients in hesitancy group were hesitant to get vaccinated, while the remaining 104 (34.8%) refused. The most common side effect was injection arm pain (n = 9, 12.3%). The common reasons for vaccine willingness was trusted in the effectiveness of the vaccine and fear of contracting COVID-19. The most common reason for vaccination hesitancy is fear of side effects, and the most effective improvement was the support from the attending physician. Factors associated with vaccine hesitancy include female sex, influenza vaccination status, awareness of the importance and safety of vaccine, attitudes of doctors and others toward vaccine, medical worker source information of vaccine, relative/friend with medical background, total score of VHS (Vaccine Hesitancy Scale), accessibility of vaccine. Conclusion: For liver transplant recipients, COVID-19 vaccine is an important preventive measure. Identifying the factors influencing COVID-19 vaccine hesitancy is therefore critical to developing a promotion plan. Our study shows that more comprehensive vaccine knowledge popularization and relevant medical workers' training can effectively improve the acceptance of COVID-19 vaccine in this population.

Diagnostic performance of magnetic resonance enterography and ultrasound in children with inflammatory bowel diseases: a diagnostic test accuracy meta-analysis.

OBJECTIVES: Magnetic resonance enterography (MRE) and ultrasound (US) can be used to diagnose inflammatory bowel diseases (IBD) in children. This meta-analysis aimed to determine the diagnostic performance of MRE and US in pediatric patients with IBD. METHODS: PubMed, Embase, and the Cochrane Library were searched for eligible studies published up to June 1, 2020. The outcomes were the performances of MRE and US at the segment and patient levels. Pooled sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR), and the area under the summary receiver operating characteristic curves value (SROC) were analyzed. RESULTS: Eight studies (340 children) were included. Compared with the reference standard, MRE showed pooled sensitivity of 93.0% (95% confidence interval (CI): 90.0-95.4%), specificity of 94.6% (95% CI: 92.1-96.5%), PLR of 11.146 (95% CI: 5.027-24.713), NLR of 0.094 (95% CI: 0.057-0.155), and DOR of 134.21 (95% CI: 40.72-442.29), with a SROC of 0.9721. Similar results were observed at the patient and segment levels. Compared with the reference standard, US had pooled sensitivity of 84.1% (95% CI: 69.9-93.4%), specificity of 82.9% (95% CI: 66.4-93.4%), PLR of 4.924 (95% CI: 2.351-10.310), NLR of 0.207 (95% CI: 0.103-0.413), and DOR of 25.919 (95% CI: 7.63-88.07), but only two studies were included. US (reader 1) had a similar diagnostic value to US (reader 2). CONCLUSIONS: The present meta-analysis shows that MRE has good performance in detecting IBD in pediatric patients. Only two studies used US, and additional studies are necessary to confirm the diagnostic performance of US for IBD in children. KEY POINTS: • MRE has good performance in the detection of IBD in pediatric patients. • Similar results were observed at the patient and segment levels for MRE. • Only two studies were included for US, without differentiating patient/segment.

Characterization of lung ultrasound imaging in preterm infants with bronchopulmonary dysplasia.

BACKGROUND: Lung ultrasound (LUS) is a bedside technique that can be used on diagnosis and follow-up of neonatal respiratory diseases. However, there are rare reports on the ultrasound features of bronchopulmonary dysplasia (BPD) which is one of the most common chronic lung diseases in preterm infants. OBJECTIVE: To describe the ultrasound features of different BPD levels, and to investigate the value of ultrasound in evaluating moderate-to-severe BPD. METHODS: In this prospective cohort study, newborns of less than 37 weeks' gestational age in neonatal intensive care unit (NICU) were included. The LUS characteristics including pleural line, alveolar-interstitial syndrome (AIS), retrodiaphragmatic hyperechogenicity and diaphragmatic morphology were observed and recorded. The reliability of LUS in evaluating moderate and severe BPD were compared and calculated. RESULTS: A total of 108 infants were enrolled in our study: 39, 24, 29, 16 infants had non, mild, moderate and severe BPD. The median(IQR) pleura thickness in the moderate-to-severe BPD group was 1.7(1.6-1.85) mm, which was thicker than that in the none-to-mild BPD infants (P < 0.001), meanwhile the proportions of rough pleural lines, diffuse AIS, retrodiaphragmatic hyperechogenicity, small cysts above the diaphragm and rough diaphragm in the moderate-to-severe BPD group were also higher than those in none-to-mild BPD group (86.7% vs 36.5, 57.8% vs 7.9%, 37.8% vs 0, 33.3% vs 0, P < 0.001). In evaluating moderate-to-severe BPD, rough pleura had 91.1% (95% confidence interval [CI]: 0.793-0.965) in sensitivity, 91.3% (95% CI: 0.797-0.966) in negative predictive value (NPV), and 66.7% (95% CI: 0.544-0.771) in specificity. Small cysts had 100% (95% CI: 0.941-1) in specificity, 100% (95% CI: 0.816-1) in positive predictive value (PPV), and 37.8% in sensitivity (95% CI: 0.251-0.524). Rough diaphragm had 100% (95% CI: 0.943-1) in sensitivity, 100% (95% CI: 0.796-1) in PPV and 33.3% (95% CI: 0.211-0.478) in specificity. CONCLUSIONS: Depending on its unique advantages such as convenient, no radiation and repeatable, LUS is a valuable imaging method in assessing the severity of BPD, especially in moderate and severe BPD.

Genetic spectrum and clinical characteristics of 3ß-hydroxy-Δ5-C27-steroid oxidoreductase (HSD3B7) deficiency in China.

BACKGROUND: Biallelic variants in HSD3B7 cause 3ß-hydroxy-Δ5-C27-steroid oxidoreductase (HSD3B7) deficiency, a life-threatening but treatable liver disease. The goal of this study was to obtain detailed information on the correlation between the genotype and phenotype of HSD3B7 deficiency and to report on responses to primary bile acid therapy. METHODS: The medical records of a cohort of 39 unrelated patients with genetically and biochemically confirmed HSD3B7 deficiency were examined to determine whether there exist genotype-phenotype relationships in this bile acid synthesis disorder. RESULTS: In all, 34 of the 44 variants identified in HSD3B7 were novel. A total of 32 patients presented early with neonatal cholestasis, and 7 presented after 1-year of age with liver failure (n = 1), liver cirrhosis (n = 3), cholestasis (n = 1), renal cysts and abnormal liver biochemistries (n = 1), and coagulopathy from vitamin K1 deficiency and abnormal liver biochemistries (n = 1). Renal lesions, including renal cysts, renal stones, calcium deposition and renal enlargement were observed in 10 of 35 patients. Thirty-three patients were treated with oral chenodeoxycholic acid (CDCA) resulting in normalization of liver biochemistries in 24, while 2 showed a significant clinical improvement, and 7 underwent liver transplantation or died. Remarkably, renal lesions in 6 patients resolved after CDCA treatment, or liver transplantation. There were no significant correlations between genotype and clinical outcomes. CONCLUSIONS: In what is the largest cohort of patients with HSD3B7 deficiency thus far studied, renal lesions were a notable clinical feature of HSD3B7 deficiency and these were resolved with suppression of atypical bile acids by oral CDCA administration.

Apoptotic body-mediated intercellular delivery for enhanced drug penetration and whole tumor destruction.

Chemotherapeutic nanomedicines can exploit the neighboring effect to increase tumor penetration. However, the neighboring effect is limited, likely by the consumption of chemotherapeutic agents and resistance of internal hypoxic tumor cells. Here, we first propose and demonstrate that apoptotic bodies (ApoBDs) could carry the remaining drugs to neighboring tumor cells after apoptosis. To enhance the ApoBD-based neighboring effect, we fabricated disulfide-linked prodrug nanoparticles consisting of camptothecin (CPT) and hypoxia-activated prodrug PR104A. CPT kills external normoxic tumor cells to produce ApoBDs, while PR104A remains inactive. The remaining drugs could be effectively delivered into internal tumor cells via ApoBDs. Although CPT exhibits low toxicity to internal hypoxic tumor cells, PR104A could be activated to exert strong cytotoxicity, which further facilitates deep penetration of the remaining drugs. Such a synergic approach could overcome the limitations of the neighboring effect to penetrate deep into solid tumors for whole tumor destruction.

Early reoccurrence of traumatic posterior atlantoaxial dislocation without fracture: A case report.

BACKGROUND: In general, atlantoaxial dislocation is rare due to the stability of the C1-C2 complex. Traumatic atlantoaxial dislocations are usually anterior and accompanied by odontoid fractures. Posterior atlantoaxial dislocations are rare, and complete posterior dislocation without associated fracture is even more rare. A case of early recurrence of posterior atlantoaxial dislocation without fracture being in therapy of first closed reduction and then open reduction has not been previously reported. CASE SUMMARY: A 45-year-old female presented with traumatic posterior atlantoaxial dislocation (TPAD) of C1-C2 without associated fractures, and Frankel Grade B spinal cord function. She was successfully managed by immediate closed reduction under skull traction. Unexpectedly, 17 d later, re-dislocation was discovered. On day 28, closed reduction was performed as before but failed. Then, open reduction and posterior internal fixation with autologous iliac bone grafts was performed. By 6 mo after surgery, atlantoaxial joint fusion was achieved, and neurological function had recovered to Frankel Grade E. At 12 mo follow-up, she had lost only 15° of cervical rotation, and atlantoaxial complex instability in joint flexing and extending were no longer observed under fluoroscopy. CONCLUSION: Early assessment of transverse ligament is critical for TPAD without fracture avoiding re-dislocation after closed reduction.

Diagnostic performance of lung ultrasound for transient tachypnea of the newborn: A meta-analysis.

Several recent studies demonstrated that lung ultrasound could achieve desired diagnostic accuracy for transient tachypnea of the neonate (TTN). However, the diagnostic performance of lung ultrasound for TTN has not been systematically studied to date. This meta-analysis aimed to investigate the performance of lung ultrasound in diagnosing TTN. The relevant literature was searched in PubMed, Medline, the Cochrane Library, and Embase databases without any restriction in terms of language and time until January 31, 2021. Studies that assessed the diagnostic performance of lung ultrasound for TTN were included. Seven studies with 1514 participants were summarized. The lung ultrasound provided more accurate performance for diagnosing TTN with pooled sensitivity and specificity of 0.67 [95% confidence interval (CI) = 0.63-0.71] and 0.97 (95% CI = 0.95-0.98), respectively. A higher summarized area under the summary receiver operating characteristic curve was observed as 0.9906. Lower sensitivity and area under the curve (AUC) of B-lines for TTN were observed as 0.330 (95% CI = 0.27-0.38) and 0.5000, respectively. Lung ultrasound provided highly accurate AUC, sensitivity, and specificity in detecting TTN. Large-scale studies are warranted in the future to confirm these results.

Ultrasound shear wave elastography: does it add value to gray-scale ultrasound imaging in differentiating biliary atresia from other causes of neonatal jaundice?

BACKGROUND: Neonatal/infantile jaundice is relatively common, and most cases resolve spontaneously. However, in the setting of unresolved neonatal cholestasis, a prompt and accurate assessment for biliary atresia is vital to prevent poor outcomes. OBJECTIVE: To determine whether shear wave elastography (SWE) alone or combined with gray-scale imaging improves the diagnostic performance of US in discriminating biliary atresia from other causes of neonatal jaundice over that of gray-scale imaging alone. MATERIALS AND METHODS: Infants referred for cholestatic jaundice were assessed with SWE and gray-scale US. On gray-scale US, two radiology readers assessed liver heterogeneity, presence of the triangular cord sign, hepatic artery size, presence/absence of common bile duct and gallbladder, and gallbladder shape; associated interobserver correlation coefficients (ICC) were calculated. SWE speeds were performed on a Siemens S3000 using 6C2 and 9 L4 transducers with both point and two-dimensional (2-D) SWE US. Both univariable and multivariable analyses were performed, as were receiver operating characteristic curves (ROC) and statistical significance tests (chi-squared, analysis of variance, t-test and Wilcoxon rank sum) when appropriate. RESULTS: There were 212 infants with biliary atresia and 106 without biliary atresia. The median shear wave speed (SWS) for biliary atresia cases was significantly higher (P<0.001) than for non-biliary-atresia cases for all acquisition modes. For reference, the median L9 point SWS was 2.1 m/s (interquartile range [IQR] 1.7-2.4 m/s) in infants with biliary atresia and 1.5 m/s (IQR 1.3-1.9 m/s) in infants without biliary atresia (P<0.001). All gray-scale US findings were significantly different between biliary-atresia and non-biliary-atresia cohorts (P<0.001), intraclass correlation coefficient (ICC) range 0.7-1.0. Triangular cord sign was most predictive of biliary atresia independent of other gray-scale findings or SWS - 96% specific and 88% sensitive. Multistep univariable/multivariable analysis of both gray-scale findings and SWE resulted in three groups being predictive of biliary atresia likelihood. Abnormal common bile duct/gallbladder and enlarged hepatic artery were highly predictive of biliary atresia independent of SWS (100% for girls and 95-100% for boys). Presence of both the common bile duct and the gallbladder along with a normal hepatic artery usually excluded biliary atresia independent of SWS. Other gray-scale combinations were equivocal, and including SWE improved discrimination between biliary-atresia and non-biliary-atresia cases. CONCLUSION: Shear wave elastography independent of gray-scale US significantly differentiated biliary-atresia from non-biliary-atresia cases. However, gray-scale findings were more predictive of biliary atresia than elastography. SWE was useful for differentiating biliary-atresia from non-biliary-atresia cases in the setting of equivocal gray-scale findings.

Identifying threshold sizes for enlarged abdominal lymph nodes in different age ranges from about 200,000 individual's data.

The threshold size for enlarged abdominal lymph nodes (E-ALNs), a common pediatric disorder, has yet to be standardized. According to the maximum short-axis diameter, this study divided ALNs into Grade A (≥ 10 mm), Grade B (8-10 mm), Grade C (5-8 mm), and Grade D (< 5 mm, normal). To identify the threshold size for E-ALNs, the prevalence of each grade was compared between asymptomatic individuals and symptomatic (e.g., abdominal pain) individuals without other diseases (e.g., appendicitis) that could explain the symptoms for different ages using data from > 200,000 individuals. The results showed the following: (1) For ages 1-3 years, the recommended threshold size is 8 mm, as the differences in the prevalence between the two groups were nonsignificant for Grade C but significant (p < 0.05) for both Grades A and B. (2) For ages 3-14 years, the recommended threshold size is 5 mm, as the differences between the two groups were significant (p < 0.05) for Grades A, B, and C. (3) The prevalence of Grades A, B, and C was very low for ages 0-1 years and high for ages 1-6 years. (4) The prevalence for males was generally higher than that for females for Grades A and B.

Integrated In Silico-In Vitro Identification and Optimization of Bone Morphogenic Protein-2 Armpit Epitope as Its Antagonist Binding Site.

Bone morphogenic protein-2 (BMP-2) is the most documented member of BMP family and plays a crucial role in bone formation and growth. In this study, we systematically analyze and compare the complex crystal structures and interaction properties of BMP-2 with its cognate receptors BMPR-I/BMPR-II and with its natural antagonist crossveinless-2 (CV-2) using an integrated in silico-in vitro strategy. It is found that the antagonist-binding site is not fully overlapped with the two receptor-binding sites on BMP-2 surface; the antagonist can competitively disrupt BMP-2-BMPR-II interaction using a blocking-out-of-site manner, but has no substantial influence on BMP-2-BMPR-I interaction. Here, the antagonist-binding site is assigned as a new functional epitope armpit to differ from the traditional conformational epitope wrist and linear epitope knuckle at receptor-binding sites. Structural analysis reveals that the armpit comprises three sequentially discontinuous, structurally vicinal peptide segments, separately corresponding to a loop region and two ß-strands crawling on the protein surface. The three segments cannot work independently when splitting from the protein context, but can restore binding capability to CV-2 if they are connected to a single peptide. A systematic combination of different-length polyglycine linkers between these segments obtains a series of designed single peptides, from which several peptides that can potently interact with the armpit-recognition site of CV-2 with high affinity and specificity are identified using energetic analysis and fluorescence assay; they are expected to target BMP-2-CV-2 interaction in a self-inhibitory manner.

In situ low-immunogenic albumin-conjugating-corona guiding nanoparticles for tumor-targeting chemotherapy.

Nanoparticles (NPs) are unavoidably covered by a layer of immunogenic proteins upon injection into blood, such as immunoglobins and complements, which buries the active-targeting ligands and triggers the rapid clearance of NPs by the mononuclear phagocytic system. Low antifouling polyethylene glycol is used to inhibit the formation of the immunogenic corona but it leads to poor cellular uptake and the immunogen-related accelerated blood clearance (ABC) phenomenon in multiple administrations. Here, we develop surface maleimide-modified NPs that covalently conjugate in vivo plasma albumin in its corona upon exposure to blood. The in situ recruited low-immunogenic albumin-enriching corona is capable of protecting maleimide-decorated NPs from phagocytosis in the bloodstream, preventing the ABC phenomenon in the second administration, facilitating NP accumulation in the tumor site/cells by the passive EPR effect and albumin receptor-mediated active targeting, and finally improving the antitumor activity. Such findings suggest that the facile strategy, based on the in situ anchored albumin-enriching corona, is efficient at enabling maleimide-decorated NPs to acquire stealth and tumor-targeting ability.

Intestinal absorption and activation of decitabine amino acid ester prodrugs mediated by peptide transporter PEPT1 and enterocyte enzymes.

Decitabine (DAC), a potent DNA methyltransferase (DNMT) inhibitor, has a limited oral bioavailability. Its 5'-amino acid ester prodrugs could improve its oral delivery but the specific absorption mechanism is not yet fully understood. The aim of this present study was to investigate the in vivo absorption and activation mechanism of these prodrugs using in situ intestinal perfusion and pharmacokinetics studies in rats. Although PEPT1 transporter is pH dependent, there appeared to be no proton cotransport in the perfusion experiment with a preferable transport at pH 7.4 rather than pH 6.5. This suggested that the transport was mostly dependent on the dissociated state of the prodrugs and the proton gradient might play only a limited role. In pH 7.4 HEPES buffer, an increase in Peff was observed for L-val-DAC, D-val-DAC, L-phe-DAC and L-trp-DAC (2.89-fold, 1.2-fold, 2.73-fold, and 1.90-fold, respectively), compared with the parent drug. When co-perfusing the prodrug with Glysar, a known substrate of PEPT1, the permeabilities of the prodrugs were significantly inhibited compared with the control. To further investigate the absorption of the prodrugs, L-val-DAC was selected and found to be concentration-dependent and saturable, suggesting a carrier-mediated process (intrinsic Km: 7.80 ±â€¯2.61 mM) along with passive transport. Determination of drug in intestinal homogenate after perfusion further confirmed that the metabolic activation mainly involved an intestinal first-pass effect. In a pharmacokinetic evaluation, the oral bioavailability of L-val-DAC, L-phe-DAC and L-trp-DAC were nearly 1.74-fold, 1.69-fold and 1.49-fold greater than that of DAC. The differences in membrane permeability and oral bioavailability might be due to the different stability in the intestinal lumen and the distinct PEPT1 affinity which is mainly caused by the stereochemistry, hydrophobicity and steric hindrance of the side chains. In summary, the detailed investigation of the absorption mechanism by in vivo intestinal perfusion and pharmacokinetic studies showed that the prodrugs of DAC exhibited excellent permeability and oral bioavailability, which might be attributed to a hybrid (partly PEPT1-mediated and partly passive) transport mode and a rapid activation process in enterocytes.