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1.
J Am Chem Soc ; 146(13): 8832-8838, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38507251

ABSTRACT

How mutations impact protein stability and structure dynamics is crucial for understanding the pathological process and rational drug design. Herein, we establish a time-resolved native mass spectrometry (TR-nMS) platform via a rapid-mixing capillary apparatus for monitoring the acid-initiated protein unfolding process. The molecular details in protein structure unfolding are further profiled by a 193 nm ultraviolet photodissociation (UVPD) analysis of the structure-informative photofragments. Compared with the wild-type dihydrofolate reductase (WT-DHFR), the M42T/H114R mutant (MT-DHFR) exhibits a significant stability decrease in TR-nMS characterization. UVPD comparisons of the unfolding intermediates and original DHFR forms indicate the special stabilization effect of cofactor NADPH on DHFR structure, and the M42T/H114R mutations lead to a significant decrease in NADPH-DHFR interactions, thus promoting the structure unfolding. Our study paves the way for probing the mutation-induced subtle changes in the stability and structure dynamics of drug targets.


Subject(s)
Escherichia coli , Protein Unfolding , Escherichia coli/metabolism , NADP/metabolism , Protein Stability , Mutation , Mass Spectrometry , Tetrahydrofolate Dehydrogenase/metabolism
2.
RSC Adv ; 14(12): 8075-8080, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38464689

ABSTRACT

The incorporation of deuterium into peptides and proteins holds broad applications across various fields, such as drug development and structural characterization. Nevertheless, current methods for peptide/protein deuteration often target exchangeable labile sites or require harsh conditions for stable modification. In this study, we present a late-stage approach utilizing an alkaline phosphate solution to achieve deuteration of non-exchangeable backbone sites of peptides and proteins. The specific deuteration regions are identified through ultraviolet photodissociation (UVPD) and mass spectrometry analysis. This deuteration strategy demonstrates site and structure selectivity, with a notable affinity for labeling the α-helix regions of myoglobin. The deuterium method is particularly suitable for peptides and proteins that remain stable under high pH conditions.

3.
Chem Sci ; 15(7): 2545-2557, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38362424

ABSTRACT

Due to the complex high-order structures and interactions of proteins within an aqueous solution, a majority of chemical functionalizations happen on the hydrophilic sites of protein external surfaces which are naturally exposed to the solution. However, the hydrophobic pockets inside proteins are crucial for ligand binding and function as catalytic centers and transporting tunnels. Herein, we describe a reagent pre-organization and in situ photochemical trifluoromethylation strategy to profile the functional sites inside the hydrophobic pockets of native proteins. Unbiased mass spectrometry profiling was applied for the characterization of trifluoromethylated sites with high sensitivity. Native proteins including myoglobin, trypsin, haloalkane dehalogenase, and human serum albumin have been engaged in this mild photochemical process and substantial hydrophobic site-specific and structure-selective trifluoromethylation substitutes are obtained without significant interference to their bioactivity and structures. Sodium triflinate is the only reagent required to functionalize the unprotected proteins with wide pH-range tolerance and high biocompatibility. This "in-pocket" activation model provides a general strategy to modify the potential binding pockets and gain essential structural insights into the functional hotspots inside protein hydrophobic pockets.

4.
Sci Rep ; 13(1): 21886, 2023 12 11.
Article in English | MEDLINE | ID: mdl-38081976

ABSTRACT

The present study aimed to investigate the biomechanical and histomorphological features of mandibles in an adenine-induced chronic kidney disease-mineral and bone disorder (CKD-MBD) rat model of CKD. A total of 14 Sprague-Dawley rats were randomized into the following two groups: control group and CKD group. At the end of the sixth week, all rats were euthanized, and serum was collected for biochemical marker tests. Macroscopic bone growth and biomechanical parameters were measured in the right hemimandible, while the left hemimandible was used for bone histomorphometric analysis. Compared to the control group, the CKD group showed a significant increase in serum creatinine, blood urea nitrogen, and serum parathyroid hormone at the end of the sixth week. The biomechanical structural properties significantly decreased in the CKD group compared to the control group. Bone histomorphometric analysis indicated that the trabecular bone volume of rats in the CKD group was significantly lower than that of the control group. In the CKD groups, the bone formation parameters of the trabecular bone were significantly increased, while the bone mineralization apposition rates of both the trabecular bone and periosteal cortical bone were significantly increased. The rat CKD model showed deteriorated structural mechanics, low trabecular bone volume, high trabecular bone formation, increased trabecular bone mineralization apposition rate, and increased cortical bone mineralization apposition rate, which met the characteristics of osteitis fibrosa, indicating that this model is a useful tool for the study of mandible diseases in CKD patients.


Subject(s)
Chronic Kidney Disease-Mineral and Bone Disorder , Renal Insufficiency, Chronic , Humans , Rats , Animals , Rats, Sprague-Dawley , Parathyroid Hormone , Mandible
5.
Quant Imaging Med Surg ; 13(12): 8067-8078, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-38106326

ABSTRACT

Background: Teratomas are the most common germ cell tumors in children, and histologically classified as mature teratomas (MTs) and immature teratomas (ITs). Preoperative IT identification can affect the surgical approach, the type of procedure, and future possible reproductive health. However, there is no complete diagnostic criterion for ITs nowadays. We aimed to establish and validate a nomogram based on clinical and computed tomography (CT) features for preoperative prediction of ITs in children. Methods: We retrospectively reviewed 519 teratoma patients from hospital I for training (n=364) and validation (n=155), and 113 patients from hospital II for external validation. Univariate and multivariate logistic regression analyses were performed on the training set to screen risk factors, including alpha-fetoprotein (AFP), age, gender, tumor site, size, tumor composition, calcification and fat. Then, a nomogram was established based on identified risk factors and validated on the validation set. The performance of the nomogram was evaluated in terms of discrimination, calibration and the clinical usefulness. Results: Multivariate logistic regression showed that tumor composition, AFP, age, calcification and fat were independent risk factors for preoperative prediction of IT. The area under the receiver operating characteristic (ROC) curves (AUCs) for the nomogram on the training set, internal and external validation set were 0.92 (0.88-0.96), 0.91 (0.84-0.97) and 0.92 (0.86-0.97), respectively. The model demonstrated sensitivity of 80%, specificity of 90% at the cut-off value of 0.262. Whatever the set, the calibration curve indicated good calibration. Decision curve analysis (DCA) curves demonstrated that the nomogram had greater net benefits than either the treat-all tactics or the treat-none tactics within a large scope of threshold. Conclusions: The nomogram established based on clinical and CT findings had the favorable accuracy for the preoperative prediction of IT, and may help in clinical decision-making and risk stratification.

6.
Front Pediatr ; 11: 1199224, 2023.
Article in English | MEDLINE | ID: mdl-37520052

ABSTRACT

Aim: Congenital hepatoblastoma, a rare malignant liver tumor in infancy, typically presents with abdominal distension or mass. Tumors detected antenatally or during the first three months of age are considered congenital hepatoblastoma. Hepatic arteriovenous fistulas (HAVF) are associated with high mortality in the neonatal period and can be caused by many secondary factors. This case report focuses on a patient with congenital hepatoblastoma accompanied by HAVF, highlighting the clinical and imaging characteristics and management strategies. Case presentation: A term infant presented with sudden tachypnea and heart failure on his first day of life. A cystic-solid mixed lesion in the fetus's liver was detected by an antenatal ultrasound scan. Postnatal digital subtraction angiography confirmed the presence of arteriovenous fistulas, which were treated with trans-arterial embolization. However, despite the intervention, the patient's heart failure did not improve. The patient underwent a left hepatectomy, and hepatoblastoma was discovered by histology of the resected hepatic lobe. Unfortunately, metastases were later discovered in the intracranial and ocular regions. Ultimately, the family decided to discontinue further treatment. Conclusion: Congenital hepatoblastoma presenting with hepatic arteriovenous fistulas has not been previously described. Hepatoblastoma should be considered when alpha-fetoprotein levels show a significant elevation in newborns. Prenatal diagnosis may improve pre- and postnatal management.

7.
Quant Imaging Med Surg ; 13(5): 3001-3012, 2023 May 01.
Article in English | MEDLINE | ID: mdl-37179906

ABSTRACT

Background: The diagnosis and treatment of childhood neuroblastoma (NB) varies with different risk groups, thus requiring accurate preoperative risk assessment. This study aimed to verify the feasibility of amide proton transfer (APT) imaging in risk stratification of abdominal NB in children, and compare it with the serum neuron-specific enolase (NSE). Methods: This prospective study enrolled 86 consecutive pediatric volunteers with suspected NB, and all subjects underwent abdominal APT imaging on a 3T magnetic resonance imaging scanner. A 4-pool Lorentzian fitting model was used to mitigate motion artifacts and separate the APT signal from the contaminating ones. The APT values were measured from tumor regions delineated by two experienced radiologists. The one-way analysis of variance, independent-sample t-test, Mann-Whitney U-test, and receiver operating characteristic analysis were performed to evaluate and compare the risk stratification performance of the APT value and serum NSE index-a routine biomarker of NB in clinics. Results: Thirty-four cases (mean age, 38.6±32.4 months; 5 very-low-risk, 5 low-risk, 8 intermediate-risk and 16 high-risk ones) were included in the final analysis. The APT values were significantly higher in high-risk NB (5.80%±1.27%) than in the non-high-risk group (3.88%±1.01%) composed of the other three risk groups (P<0.001). However, there was no significant difference (P=0.18) in NSE levels between the high-risk (93.05±97.14 ng/mL) and non-high-risk groups (41.45±30.99 ng/mL). The associated area under the curve (AUC) of the APT parameter (AUC =0.89) in differentiating high-risk NB from non-high-risk NB was significantly higher (P=0.03) than that of NSE (AUC =0.64). Conclusions: As an emerging non-invasive magnetic resonance imaging technique, APT imaging has a promising prospect for distinguishing high-risk NB from non-high-risk NB in routine clinical applications.

8.
J Am Chem Soc ; 145(21): 11477-11481, 2023 05 31.
Article in English | MEDLINE | ID: mdl-37207290

ABSTRACT

The rational design and development of effective inhibitors for cyclin-dependent kinases 12 and 13 (CDK12 and CDK13) are largely dependent on the understanding of the dynamic inhibition conformations but are difficult to be achieved by conventional characterization tools. Herein, we integrate the structural mass spectrometry (MS) methods of lysine reactivity profiling (LRP) and native MS (nMS) to systematically interrogate both the dynamic molecular interactions and overall protein assembly of CDK12/CDK13-cyclin K (CycK) complexes under the modulation of small molecule inhibitors. The essential structure insights, including inhibitor binding pocket, binding strength, interfacial molecular details, and dynamic conformation changes, can be derived from the complementary results of LRP and nMS. We find the inhibitor SR-4835 binding can greatly destabilize the CDK12/CDK13-CycK interactions in an unusual allosteric activation way, thereby providing a novel alternative for the kinase activity inhibition. Our results underscore the great potential of LRP combination with nMS for the evaluation and rational design of effective kinase inhibitors at the molecular level.


Subject(s)
Cyclin-Dependent Kinases , Cyclins , Cyclin-Dependent Kinases/chemistry , Allosteric Regulation , Phosphorylation , Cyclins/chemistry , Cyclins/metabolism , Mass Spectrometry
9.
World J Pediatr Surg ; 6(3): e000531, 2023.
Article in English | MEDLINE | ID: mdl-37223779

ABSTRACT

Background: Preoperative imaging assessment of surgical risk is very important for the prognosis of these children. To develop and validate a radiomics-based machine learning model based on the analysis of radiomics features to predict surgical risk in children with abdominal neuroblastoma (NB). Methods: A retrospective study was conducted from April 2019 to March 2021 among 74 children with abdominal NB. A total of 1874 radiomic features in MR images were extracted from each patient. Support vector machines (SVMs) were used to establish the model. Eighty percent of the data were used as the training set to optimize the model, and 20% of the data were used to validate its accuracy, sensitivity, specificity and area under the curve (AUC) to verify its effectiveness. Results: Among the 74 children with abdominal NB, 55 (65%) had surgical risk and 19 (35%) had no surgical risk. A t test and Lasso identified that 28 radiomic features were associated with surgical risk. After developing an SVM-based model using these features, predictions were made about whether children with abdominal NB had surgical risk. The model achieved an AUC of 0.94 (a sensitivity of 0.83 and a specificity of 0.80) with 0.890 accuracy in the training set and an AUC of 0.81 (a sensitivity of 0.73 and a specificity of 0.82) with 0.838 accuracy in the test set. Conclusions: Radiomics and machine learning can be used to predict the surgical risk in children with abdominal NB. The model based on 28 radiomic features established by SVM showed good diagnostic efficiency.

10.
Front Med (Lausanne) ; 10: 1088815, 2023.
Article in English | MEDLINE | ID: mdl-37020672

ABSTRACT

Lobular capillary hemangioma (LCH), previously known as pyogenic granuloma, is a benign vascular lesion commonly found within the oral and nasal cavities. However, it is rarely encountered within the trachea, especially in pediatric patients, where it manifests as hemoptysis, cough, and wheeze, and is frequently misdiagnosed as bronchitis or asthma. There is limited literature on the presentation, behavior, and management of tracheal LCH. Herein, we describe a rare case of tracheal LCH in an 11-year-old boy with a history of hemoptysis, which was successfully managed with arterial embolization followed by electrocautery loop snaring via flexible bronchoscopy. No complications occurred during and after the procedure. A review of the relevant literature is also provided. Our case is unique, given the therapeutic strategy utilized for pediatric tracheal LCH, and reminds physicians to be aware of tracheal LCH in the differential diagnosis for hemoptysis.

11.
J Magn Reson Imaging ; 58(6): 1977-1987, 2023 12.
Article in English | MEDLINE | ID: mdl-36995000

ABSTRACT

BACKGROUND: Idiopathic central precocious puberty (ICPP) impairs child development, without early intervention. The current reference standard, the gonadotropin-releasing hormone stimulation test, is invasive which may hinder diagnosis and intervention. PURPOSE: To develop a model for accurate diagnosis of ICPP, by integrating pituitary MRI, carpal bone age, gonadal ultrasound, and basic clinical data. STUDY TYPE: Retrospective. POPULATION: A total of 492 girls with PP (185 with ICPP and 307 peripheral precocious puberty [PPP]) were randomly divided by reference standard into training (75%) and internal validation (25%) data. Fifty-one subjects (16 with ICPP, 35 with PPP) provided by another hospital as external validation. FIELD STRENGTH/SEQUENCE: T1-weighted (spin echo [SE], fast SE, cube) and T2-weighted (fast SE-fat suppression) imaging at 3.0 T or 1.5 T. ASSESSMENT: Radiomics features were extracted from pituitary MRI after manual segmentation. Carpal bone age, ovarian, follicle and uterine volumes and endometrium presence were assessed from radiographs and gonadal ultrasound. Four machine learning methods were developed: a pituitary MRI radiomics model, an integrated image model (with pituitary MRI, gonadal ultrasound and bone age), a basic clinical model (with age and sex hormone data), and an integrated multimodal model combining all features. STATISTICAL TESTS: Intraclass correlation coefficients were used to assess consistency of segmentation. Receiver operating characteristic (ROC) curves and the Delong tests were used to assess and compare the diagnostic performance of models. P < 0.05 was considered statistically significant. RESULTS: The area under of the ROC curve (AUC) of the pituitary MRI radiomics model, integrated image model, basic clinical model, and integrated multimodal model in the training data was 0.668, 0.809, 0.792, and 0.860. The integrated multimodal model had higher diagnostic efficacy (AUC of 0.862 and 0.866 for internal and external validation). CONCLUSION: The integrated multimodal model may have potential as an alternative clinical approach to diagnose ICPP. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.


Subject(s)
Puberty, Precocious , Female , Child , Humans , Puberty, Precocious/diagnostic imaging , Retrospective Studies , Magnetic Resonance Imaging , Uterus , Endometrium
12.
ACS Appl Mater Interfaces ; 15(14): 17592-17600, 2023 Apr 12.
Article in English | MEDLINE | ID: mdl-36988558

ABSTRACT

H-bond networks at heterogeneous interfaces play crucial roles in bioseparation, biocatalysis, biochip array profiling, and functional nanosystem self-assembly, but their precise modulation and enhancement remain challenging. In this study, we have discovered that interfacial hydrophobic hydration significantly enhances H-bond networks at the interface between a glycan-modified adsorbent and a methanol-water-acetonitrile ternary solution. The enhanced H-bond networks greatly promote the adsorbent-solution heterogeneous glycan-glycan recognition and interaction. This novel hydrophobic hydration-enhanced hydrophilic interaction (HEHI) strategy improves the affinity and efficiency of intact glycopeptide enrichment. Compared with the commonly used hydrophilic-interaction enrichment strategy, 23.5 and 48.5% more intact N- and O-glycopeptides are identified, and the enrichment recoveries of half of the glycopeptides are increased >100%. Further, in-depth profiling of both N- and O-glycosylation occurring on SARS-CoV-2 S1 and hACE2 proteins has been achieved with more glycan types and novel O-glycosylation information involved. Interfacial hydrophobic hydration provides a powerful tool for the modulation of hydrophilic interactions in biological systems.


Subject(s)
COVID-19 , Humans , SARS-CoV-2 , Glycosylation , Glycopeptides/chemistry , Polysaccharides/chemistry , Hydrophobic and Hydrophilic Interactions
13.
J Magn Reson Imaging ; 57(4): 1131-1142, 2023 04.
Article in English | MEDLINE | ID: mdl-35861468

ABSTRACT

BACKGROUND: Diffusion MRI (dMRI) is known to be sensitive to hypoxic-ischemic encephalopathy (HIE). However, existing dMRI studies used simple diffusion tensor metrics and focused only on a few selected cerebral regions, which cannot provide a comprehensive picture of microstructural injury. PURPOSE: To systematically characterize the microstructural alterations in mild, moderate, and severe HIE neonates compared to healthy neonates with advanced dMRI using region of interest (ROI), tract, and fixel-based analyses. STUDY TYPE: Prospective. POPULATION: A total of 42 neonates (24 males and 18 females). FIELD STRENGTH/SEQUENCE: 3-T, diffusion-weighted echo-planar imaging. ASSESSMENT: Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD), fiber density (FD), fiber cross-section (FC), and fiber density and cross-section (FDC) were calculated in 40 ROIs and 6 tracts. Fixel-based analysis was performed to assess group differences in individual fiber components within a voxel (fixel). STATISTICAL TESTS: One-way analysis of covariance (ANCOVA) to compare dMRI metrics among severe/moderate/mild HIE and control groups and general linear model for fixel-wise group differences (age, sex, and body weight as covariates). Adjusted P value < 0.05 was considered statistically significant. RESULTS: For severe HIE, ROI-based analysis revealed widespread regions, including the deep nuclei and white matter with reduced FA, while in moderate injury, only FC was decreased around the posterior watershed zones. Tract-based analysis demonstrated significantly reduced FA, FD, and FC in the right inferior fronto-occipital fasciculus (IFOF), right inferior longitudinal fasciculus (ILF), and splenium of corpus callosum (SCC) in moderate HIE, and in right IFOF and left anterior thalamic radiation (ATR) in mild HIE. Correspondingly, we found altered fixels in the right middle-posterior IFOF and ILF, and in the central-to-right part of SCC in moderate HIE. DATA CONCLUSION: For severe HIE, extensive microstructural injury was identified. For moderate-mild HIE, association fiber injury in posterior watershed area with a rightward lateralization was found. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 3.


Subject(s)
Diffusion Tensor Imaging , Hypoxia-Ischemia, Brain , Male , Infant, Newborn , Female , Humans , Diffusion Tensor Imaging/methods , Prospective Studies , Diffusion Magnetic Resonance Imaging , Ischemia
14.
Sci Rep ; 12(1): 21475, 2022 12 12.
Article in English | MEDLINE | ID: mdl-36509884

ABSTRACT

The wind load a tree withstood is mainly applied to its crown, whose morphology and structure directly affect the degree of wind load given a certain wind condition. Though the features of tree crown are relatively easy to measure, however, among them which is/are the determining factor and how they contribute to wind load remain unknown. In order to figure out how crown features of different tree species influence the wind load, the wind tunnel experiment was performed for 7 most used urban greening tree species, and laser scanning was used to measure the accurate crown features. The results derived by multiple linear model showed (1) Ficus concinna, Dracontomelon duperreanum, Ormosia pinnata and Bischofia javanica are recommended in urban greening for suffering the smaller wind load under the same conditions, whereas Schefflera macrostachya, Acacia confusa and Khaya senegalensis are inadequate towards the view of crown features; (2) crown features like crown horizontal ratio, windward side projection and porosity ratio are important in estimating wind load. Our study demonstrated that evaluating the wind load via crown features is feasible, and provided valuable suggestion for selecting idealized decorative trees in urban environment with a smaller wind load due to the crown features.


Subject(s)
Light , Trees , Trees/anatomy & histology , Lasers
15.
Genes (Basel) ; 13(11)2022 10 22.
Article in English | MEDLINE | ID: mdl-36360161

ABSTRACT

Studies of local adaptation in populations of chinaberry (Melia azedarach L.) are important for clarifying patterns in the population differentiation of this species across its natural range. M. azedarach is an economically important timber species, and its phenotype is highly variable across its range in China. Here, we collected M. azedarach seeds from 31 populations across its range and conducted a common garden experiment. We studied patterns of genetic differentiation among populations using molecular markers (simple sequence repeats) and data on phenotypic variation in six traits collected over five years. Our sampled populations could be subdivided into two groups based on genetic analyses, as well as patterns of isolation by distance and isolation by environment. Significant differentiation in growth traits was observed among provenances and families within provenances. Geographic distance was significantly correlated with the quantitative genetic differentiation (QST) in height (HEIT) and crown breadth. Climate factors were significantly correlated with the QST for each trait. A total of 23 climatic factors were examined. There was a significant effect of temperature on all traits, and minimum relative humidity had a significant effect on the survival rate over four years. By comparing the neutral genetic differentiation (FST) with the QST, the mode of selection acting on survival rate varied, whereas HEIT and the straightness of the main trunk were subject to the same mode of selection. The variation in survival rate was consistent with the variation in genetic differentiation among populations, which was indicative of local adaptation. Overall, our findings provide new insights into the responses of the phenological traits of M. azedarach to changes in the climate conditions of China.


Subject(s)
Melia azedarach , Melia azedarach/genetics , Quantitative Trait, Heritable , Genetic Variation , Climate , Microsatellite Repeats
16.
World J Clin Cases ; 10(21): 7429-7437, 2022 Jul 26.
Article in English | MEDLINE | ID: mdl-36158007

ABSTRACT

BACKGROUND: Sporadic cases of extranasopharyngeal angiofibroma in children, especially preschool children, have been reported in the literature. CASE SUMMARY: We present a case of extranasopharyngeal angiofibroma in a 4-year-old boy. The presenting symptoms, imaging findings, treatment, histological appearance, and follow-up data are described in detail. For this patient, we performed embolization on two occasions, and then, resected the tumor completely. During the treatment, the patient developed a soft-palate perforation due to aseptic necrosis. However, the healing ability was good, and the perforation healed spontaneously. We additionally reviewed all pediatric cases of extranasopharyngeal angiofibroma published up to 30 June 2020 in the PubMed, Baidu Scholar, Scopus, and Web of Science databases. We identified 45 pediatric patients [average (10.98 ± 4.86), boys 39 (86.7%)]. The highest proportion of cases occurred in adolescence [22 (48.9%)]. The top three sites of occurrence of extranasopharyngeal angiofibroma in children were the maxillary sinus, nasal septum, and inferior turbinate. CONCLUSION: Extranasopharyngeal angiofibromas can occur throughout childhood, and predominantly present with nasal obstruction and spontaneous rhinorrhagia.

17.
World J Clin Cases ; 10(19): 6437-6445, 2022 Jul 06.
Article in English | MEDLINE | ID: mdl-35979288

ABSTRACT

BACKGROUND: Undifferentiated embryonal sarcoma of the liver (UESL) is a rare and aggressive mesenchymal tumor in children. Herein, we describe our experience in neoadjuvant therapy (NAT) and subsequent surgery for the treatment of UESL in children. AIM: To evaluate the efficacy of NAT and explore a new choice for successful operation of UESL in children. METHODS: We retrospectively analyzed six patients newly diagnosed with unresectable UESL who received NAT and then surgery at our center between January 2004 and December 2019. The tumor was considered unresectable if it involved a large part of both lobes of the liver or had invaded the main hepatic vessels or inferior vena cava. The NAT included preoperative transcatheter arterial chemoembolization (TACE) and systemic chemotherapy. The patients were 4 boys and 2 girls with a mean age of 7 years. The longest tumor at presentation ranged from 8.6 to 14.8 cm (mean, 12 cm). Extrahepatic metastases were present in 2 cases. Preoperative systemic chemotherapy was administered 3 wk after TACE. Tumor resection was performed 3 wk after one or two cycles of NAT. The patients received systemic chemotherapy after surgery. RESULTS: All patients successfully underwent NAT and complete resection. The tumor volumes decreased by 18.2%-68.7%, with a mean decrease of 36% after 1 cycle of NAT (t = 3.524, P = 0.017). According to the Response Evaluation Criteria In Solid Tumors criteria, 4 patients had a partial response and underwent surgery, while 2 had stable disease and received another cycle of NAT before surgery. Massive tumor necrosis was seen on pathological examination of the surgical specimen: > 90% necrosis in two, > 50% necrosis in three, and 25% necrosis in 1, with an average of 71.8%. Post-NAT complications included fever, nausea and vomiting, and mild bone marrow suppression. Elevated alanine transaminase levels occurred in all patients, which returned to normal within 7-10 d after treatment. No cardiac or renal toxicity, severe hepatic dysfunction, bleeding and non-target embolization were observed in the patients. The median follow-up period was 8 years with an overall survival of 100%. CONCLUSION: NAT effectively reduced tumor volume, cleared the tumor margin, and caused massive tumor necrosis. This may be a promising choice for successful surgery of UESL in children.

18.
Chemosphere ; 307(Pt 1): 135601, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35817191

ABSTRACT

Micro/nanoplastics (MNPs) are widespread environmental pollutants that cause high health risks. However, high heterogeneity in particle sizes and chemical compositions of MNPs make their accurate characterization extremely challenging. Herein, we established a matrix-assisted laser desorption ionization-Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR MS) strategy for the unambiguous characterization of different types of MNPs with high performance, including polystyrene, polyethylene glycol terephthalate, polyamide, polymethyl methacrylate, acrylonitrile butadiene styrene copolymer, and polycarbonate. The MNP sample preparation and detection conditions were systematically optimized by using response surface methodology, and the MS detection signal-to-noise ratios were improved 1.5 times on average. The ultrahigh mass resolution of FTICR MS is crucial to the unambiguous elucidation of MNP structures. We demonstrate that this MS strategy is highly efficient in the characterization of polymer constitutions of environmental MNPs derived from foam, bottles, cable ties, and compact discs, providing a promising tool for MNP detection and safety evaluation.


Subject(s)
Acrylonitrile , Environmental Pollutants , Butadienes , Environmental Pollutants/analysis , Fourier Analysis , Microplastics , Nylons , Polyethylene Glycols , Polymers , Polymethyl Methacrylate , Polystyrenes/analysis , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods
19.
Front Neurosci ; 16: 949230, 2022.
Article in English | MEDLINE | ID: mdl-35864988

ABSTRACT

Exuberant axon growth and competitive pruning lead to dramatic and comprehensive changes in white matter pathways of the infant brain during the first few postnatal months, yet the development of structural configuration in early infancy has not been fully characterized. This study aimed to investigate the developmental trajectory of structural connectivity reflecting relative fiber density in 43 preterm-born infants aged 0-3 months of corrected age without any complications utilizing probabilistic tractography based on fiber orientation distribution and to explore the potential function correlation associated with the network properties based on the Chinese Communication Development of Infant at 10 months of corrected age. The findings revealed significant increases in global efficiency, local efficiency, normalized clustering coefficient, and small-worldness (p adj < 0.001 for each), while the normalized characteristic path length showed a non-significant decrease with age (p adj = 0.118). Furthermore, those findings were validated by another parcelation strategy. In addition, the early local efficiency was found to be significantly correlated with words understood at 10 months of corrected age. A unique developmental pattern of structural networks with enhancing efficiency and the small-world property was found in early infancy, which was different from those of neonates or toddlers. In addition, this study revealed a significant correlation between local efficiency and late language comprehension, which indicated that enhanced structural connectivity may lay the structural foundation for language specialization.

20.
Eur Radiol ; 32(4): 2158-2167, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35031842

ABSTRACT

OBJECTIVES: To evaluate the potential of molecular amide proton transfer (APT) MRI for predicting the risk group of abdominal tumors in children, and compare it with quantitative T1 and T2 mapping. METHODS: This prospective study enrolled 133 untreated pediatric patients with suspected abdominal tumors from February 2019 to September 2020. APT-weighted (APTw) imaging and quantitative relaxation time mapping sequences were executed for each subject. The region of interest (ROI) was generated with automatic artifact detection and ROI-shrinking algorithms, within which the APTw, T1, and T2 indices were calculated and compared between different risk groups. The prediction performance of different imaging parameters was assessed with the receiver operating characteristics (ROC) analysis and Student's t-test. RESULTS: Fifty-seven patients were included in the final analysis, including 24 neuroblastomas (NB), 18 Wilms' tumors (WT), and 15 hepatoblastomas (HB). The APTw signal was significantly (p < .001) higher in patients with high-risk NB than those with low-risk NB, while the difference between patients with low-risk and high-risk WT (p = .69) or HB (p = .35) was not statistically significant. The associated areas under the curve (AUC) for APT to differentiate low-risk and high-risk NB, WT, and HB were 0.93, 0.58, and 0.71, respectively. The quantitative T1 and T2 values generated AUCs of 0.61-0.70 for the risk stratification of abdominal tumors. CONCLUSIONS: APT MRI is a potential imaging biomarker for stratifying the risk group of pediatric neuroblastoma in the abdomen preoperatively and provides added value to structural MRI. KEY POINTS: • Amide proton transfer (APT) imaging showed significantly (p < .001) higher values in pediatric patients with high-risk neuroblastoma than those with low-risk neuroblastoma, but did not demonstrate a significant difference in patients with Wilms' tumor (p = .69) or hepatoblastoma (p = .35). • The associated areas under the curve (AUC) for APT to differentiate low-risk and high-risk neuroblastoma, Wilms' tumor, and hepatoblastoma were 0.93, 0.58, and 0.71, respectively. • The quantitative T1 and T2 indices generated AUCs of 0.61-0.70 for dichotomizing the risk group of abdominal tumors.


Subject(s)
Abdominal Neoplasms , Brain Neoplasms , Abdominal Neoplasms/diagnostic imaging , Amides , Child , Humans , Magnetic Resonance Imaging/methods , Prospective Studies , Protons , Risk Assessment
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