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.

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.

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.

Transdermal Adhesive Patches Loaded with Ketoprofen Evaluated by Dynamic Detection of Percutaneous Absorption.

Topical delivery has many benefits toward NSAIDs administration, and the best-selling transdermal preparation in 2015 was the NSAID patch MOHRUS®. Herein, we report a ketoprofen adhesive patch (KAP) and evaluate the penetration and absorption compared to MOHRUS®. Microdialysis sampling technique was applied to determine drug penetration in the dermis and subcutaneous tissue. Simultaneously, blood samples were withdrawn over time to obtain the drug absorption in plasma. The ketoprofen concentrations in the dermis, subcutaneous tissue, and plasma were compared with the commercially available patch (MOHRUS®). Based on the detection, pharmacokinetic parameters including Cmax, Tmax, and AUC0-8h were determined for both the formulations. No significant differences were found in the dermis, subcutaneous tissue, and plasma in rats according to the bioequivalence assessment. The KAP demonstrated multiple therapeutic advantages including the controlled drug release and the sustained drug concentration in the skin as well as in plasma. The pharmacokinetic study coupled with microdialysis sampling provided an effective strategy to evaluate transdermal delivery.

Study on Enhanced Dissolution of Azilsartan-Loaded Solid Dispersion, Prepared by Combining Wet Milling and Spray-Drying Technologies.

The purpose of this study was to develop a combination method of wet milling and spray-drying technologies to prepare the solid dispersion and improve the dissolution rate of poorly water-soluble drug candidates. Azilsartan (AZL) was selected as the model drug for its poor water solubility. In the study, AZL-loaded solid dispersion was prepared with polyethylene glycol 6000 (PEG6000) and hydroxypropyl cellulose with super low viscosity (HPC-SL) as stabilizers by using combination of wet grinding and spray-drying methods. The high AZL loading solid dispersion was then characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR). Besides, dissolution test was carried out by the paddle method and stability investigation was also conducted. As a result, the dissolution rate of the solid dispersion tablets was found to be greater than conventional tablets, but in close agreement with market tablets. Furthermore, the formulation was shown to be stable at 40 ± 2°C and 75 ± 5% for at least 6 months, owing to its decreased particle size, morphology, and its crystal form. It was concluded that the combination of wet milling and spray-drying approaches to prepare solid dispersion would be a prospective method to improve the dissolution rate of poorly water-soluble drugs.

Multifunctional Poly(methyl vinyl ether-co-maleic anhydride)-graft-hydroxypropyl-ß-cyclodextrin Amphiphilic Copolymer as an Oral High-Performance Delivery Carrier of Tacrolimus.

In order to improve oral bioavailability of tacrolimus (FK506), a novel poly(methyl vinyl ether-co-maleic anhydride)-graft-hydroxypropyl-ß-cyclodextrin amphiphilic copolymer (CD-PVM/MA) is developed, combining the bioadhesiveness of PVM/MA, P-glycoprotein (P-gp), and cytochrome P450-inhibitory effect of CD into one. The FK506-loaded nanoparticles (CD-PVM/MA-NPs) were obtained by solvent evaporation method. The physiochemical properties and intestinal absorption mechanism of FK506-loaded CD-PVM/MA-NPs were characterized, and the pharmacokinetic behavior was investigated in rats. FK506-loaded CD-PVM/MA-NPs exhibited nanometer-sized particles of 273.7 nm, with encapsulation efficiency as high as 73.3%. FK506-loaded CD-PVM/MA-NPs maintained structural stability in the simulated gastric fluid, and about 80% FK506 was released within 24 h in the simulated intestinal fluid. The permeability of FK506 was improved dramatically by CD-PVM/MA-NPs compared to its solution, probably due to the synergistic inhibition effect of P-gp and cytochrome P450 3A (CYP3A). The intestinal biodistribution of fluorescence-labeled CD-PVM/MA-NPs confirmed its good bioadhesion to the rat intestinal wall. Two endocytosis pathways, clathrin- and caveolae-mediated endocytosis, were involved in the cellular uptake of CD-PVM/MA-NPs. The important role of lymphatic transport in nanoparticles' access to the systemic circulation, about half of the contribution to oral bioavailability, was observed in mesenteric lymph duct ligated rats. The AUC0-24 of FK506 loaded in nanoparticles was enhanced up to 20-fold compared to FK506 solutions after oral administration. The present study suggested that the novel multifunctional CD-PVM/MA is a promising efficient oral delivery carrier for FK506, due to its ability in solubilization, inhibitory effects on both P-gp and CYP 3A, high bioadhesion, and sustained release capability.

A ternary system of meloxicam with matching hydrophilic polymer and cyclodextrin for improved stability in liquid preprations.

The purpose of the study is to investigate the effect of ternary systems consisting of meloxicam with cyclodextrins (HP-ß-CD or SBE-ß-CD) and different polymers (HA, HPMC and PVP) on the stability of meloxicam. The t 0.9 values of meloxicam were determined within all the aforementioned systems and the influence of various polymers on the alteration in meloxicam's stability was evaluated. All three polymers altered the stability of meloxicam to varying degrees, with the extent of the effect being related to hydrophilicity, concentration of components, and the interaction of the newly formed ternary system. Among them, meloxicam demonstrated its highest degree of stabilization within the ternary system formed by SBE-ß-CD&HPMC and HP-ß-CD&HA. We characterized the ternary system of meloxicam using differential scanning calorimetry (DSC), X-ray diffraction, and scanning electron microscopy analysis, which determined the presence of ternary system inclusions. In addition, we investigated the optimized prescription of eye drops of meloxicam using the ternary system and further determined that the ternary system improved the stability of the drug in liquid formulations.

A carrier-mediated prodrug approach to improve the oral absorption of antileukemic drug decitabine.

Decitabine (5-aza-2'-deoxycytidine, DAC) is a novel DNA methyltransferase (DNMT) inhibitor for the treatment of myelodysplastic syndrome, acute and chronic myeloid leukemia. However, it exhibits a low oral bioavailability (only 9% in mice), because of low permeability across the intestine membrane and rapid metabolism to inactive metabolite. To utilize the carrier-mediated prodrug approach for improved absorption of decitabine, a series of amino acid-decitabine conjugates were synthesized to target the intestinal membrane transporter, hPepT1. The Caco-2 permeability of the prodrugs was screened, and two l-val (aliphatic, compound 4a) and l-phe (aromatic, compound 4c) prodrugs with higher permeability were selected for further studies. The uptake of Gly-Sar by Caco-2 cells could be competitively inhibited by compounds 4a and 4c, with IC50 being 2.20 ± 0.28 mM and 3.46 ± 0.16 mM, respectively. The uptake of compounds 4a and 4c was markedly increased in the leptin-treated Caco-2 cells compared with the control Caco-2 cells, suggesting that hPepT1-mediated transport contributes to oral absorption of compounds 4a and 4c. The prodrugs were evaluated for their stability in various phosphate buffers, rat plasma, tissue homogenates, and gastrointestinal fluids. Compounds 4a and 4c were stable in gastrointestinal tract at pH 6.0 but could be quickly converted into DAC in plasma and tissue homogenates after absorption. The oral absolute bioavailability of DAC was 46.7%, 50.9%, and 26.9% after compounds 4a, 4c, and DAC were orally administered to rats at a dose of 15 mg/kg, respectively. The bioavailability of compounds 4a and 4c in rats was both reduced to about 32% when orally coadministrated with typical hPepT1 substrate Gly-Sar (150 mg/kg). Overall, compounds 4a and 4c can significantly enhance the intestinal membrane permeability of DAC, followed by rapid and mostly bioactivation to parent drug in intestinal and hepatic tissues before entry into systemic circulation, and eventually improve oral bioavailability of DAC in rats. The hPepT1-targeted prodrug strategy is a promising strategy to improve the oral bioavailability of poorly absorbed decitabine.

Enhanced oral delivery of paclitaxel using acetylcysteine functionalized chitosan-vitamin E succinate nanomicelles based on a mucus bioadhesion and penetration mechanism.

In addition to being a physiological protective barrier, the gastrointestinal mucosal membrane is also a primary obstacle that hinders the oral absorption of many therapeutic compounds, especially drugs with a poor permeability. In order to resolve this impasse, we have designed multifunctional nanomicelles based on the acetylcysteine functionalized chitosan-vitamin E succinate copolymer (CS-VES-NAC, CVN), which exhibit marked bioadhesion, possess the ability to penetrate mucus, and enhance the oral absorption of a hydrophobic drug with a poor penetrative profile, paclitaxel. The intestinal absorption (Ka = 0.38 ± 0.04 min(-1), Papp = 0.059 cm · min(-1)) of CVN nanomicelles was greatly improved (4.5-fold) in comparison with paclitaxel solution, and CLSM (confocal laser scanning microscope) pictures also showed not only enhanced adhesion to the intestinal surface but improved accumulation within intestinal villi. The in vivo pharmacokinetics indicated that the AUC0-t (586.37 ng/mL · h) of CVN nanomicelles was markedly enhanced compared with PTX solution. In summary, the novel multifunctional CVN nanomicelles appear to be a promising nanocarrier for insoluble and poorly permeable drugs due to their high bioadhesion and permeation-enhancing capability.

Structure-based prediction of human intestinal membrane permeability for rapid in silico BCS classification.

Human effective intestinal membrane permeability (Peff) is one of the two important indicators for drug classification according to the Biopharmaceutical Classification System (BCS), and contributes greatly to the performance of oral drug absorption. Here, a structure-based in silico predictive model of Peff was developed successfully to facilitate in silico BCS classification in the early stage of drug discovery, even before the compound was synthesized. The quantitative structure-Peff relationship for 30 drugs was constructed based on seven structural parameters. Then the model was built by the multiple linear regression method and internally validated by the residual analysis, the normal probability-probability plot and the Williams plot. For the entire data set, the R² and adjusted R² values were 0.782 and 0.712, respectively. The results indicated that the fitted model was robust, stable and satisfied all the prerequisites of the regression models. As for the 102 tested drugs, the predicted Peff values had a good correlation with the experimental human absorbed fraction (Fa). This model was also used to perform high/low Peff classification for 57 drugs that have been classified according to the BCS, and 72% of drugs could be classified correctly, indicating that the developed model can be used for rapid BCS classification in the early stages of drug discovery.

Endoscopic fluorescence lifetime imaging for in vivo intraoperative diagnosis of oral carcinoma.

A clinically compatible fluorescence lifetime imaging microscopy (FLIM) system was developed. The system was applied to intraoperative in vivo imaging of head and neck squamous cell carcinoma (HNSCC). The endoscopic FLIM prototype integrates a gated (down to 0.2 ns) intensifier imaging system and a fiber-bundle endoscope (0.5-mm-diameter, 10,000 fibers with a gradient index lens objective 0.5 NA, 4-mm field of view), which provides intraoperative access to the surgical field. Tissue autofluorescence was induced by a pulsed laser (337 nm, 700 ps pulse width) and collected in the 460 ± 25 nm spectral band. FLIM experiments were conducted at 26 anatomic sites in ten patients during head and neck cancer surgery. HNSCC exhibited a weaker florescence intensity (~50% less) when compared with healthy tissue and a shorter average lifetime (τ(HNSCC) = 1.21 ± 0.04 ns) than the surrounding normal tissue (τN = 1.49 ± 0.06 ns). This work demonstrates the potential of FLIM for label-free head and neck tumor demarcation during intraoperative surgical procedures.

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.

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.

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.

A fluorescence lifetime imaging classification method to investigate the collagen to lipid ratio in fibrous caps of atherosclerotic plaque.

BACKGROUND AND OBJECTIVE: This study describes a novel fluorescence lifetime imaging (FLIM) classification method to determine the ratio of collagen to lipid content in the fibrous cap of atherosclerotic plaques. Additionally, an analytical process to assess risk of plaque rupture based on this ratio is proposed. Collagen to lipid ratio has been shown to be an important parameter to evaluate structural integrity of the fibrous cap. FLIM and other time-resolved fluorescence techniques have recently been applied to the study of atherosclerosis based on the ability to assess biochemical composition. STUDY DESIGN/MATERIALS AND METHODS: Autofluorescence of specimens retrieved during carotid endarterectomy procedures was measured through three optical filters, F377: 377/50 nm, F460: 460/66 nm, and F510: 510/84 nm (center wavelength/bandwidth). A Laguerre deconvolution technique was used for the evaluation of fluorescence decay dynamics. The resulting decay parameters (average fluorescence lifetime and 4 Laguerre coefficients at each of the recorded bandwidths) were used for sample characterization. Linear discriminant analysis (LDA) was used to classify each image into collagen or lipid-rich regions based on these parameters. Ultimately, a risk-level was assigned based on the ratio of collagen to lipid on the surface of the fibrous cap. RESULTS: FLIM images were acquired in 18 carotid plaque specimens at 43 locations. Classification of collagen and lipid-rich regions within the fibrous cap was performed with sensitivity and specificity of 80% and 82%, respectively. CONCLUSIONS: Results from this study show that an LDA method of classifying regions of FLIM images of carotid plaque into collagen and lipid-rich regions is capable of being automated and used to rate the risk of plaque rupture based on autofluorescence decay dynamics and without the need for fluorescence intensity or contrast agents.

Considerations in the development of an in vitro dissolution condition for lacidipine tablets: in vivo pharmacokinetic evaluation.

In this study, a new discriminative dissolution condition for lacidipine tablets was developed by the established in vitro-in vivo relationship. Series of dissolution media of phosphate buffer solution (PBS) covering the pH range of 1-7.2 and pH 6.8 PBS containing different concentrations of sodium dodecyl sulfate (SDS), were prepared and used to investigate the dissolution behavior of lacidipine tablets. There was an obvious difference in the dissolution profiles of the both brands in pH 6.8 PBS medium containing 0.1% SDS. The pharmacokinetic study of the two lacidipine tablets was carried out in the healthy beagle dogs at a single dose of 4 mg. Statistical comparison of the AUC(0₋24), C(max), and T(max) showed a significant difference in the two brand tablets, coinciding with the dissolution performance with pH 6.8 PBS containing 0.1% SDS. The superiority of the proposed system, pH 6.8 PBS containing 0.1% SDS, could serve as a dissolution medium for lacidipine tablets, and more important it could discriminate the in vivo pharmacokinetic behavior for different brands of products. In summary, in vivo pharmacokinetic evaluation is essential to develop an appropriate in vitro dissolution condition for oral solid dosage forms of poorly soluble drugs.

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.

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.

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.