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1.
Artigo em Inglês | MEDLINE | ID: mdl-33595760

RESUMO

Quantitative myocardial contrast echocardiography (MCE) has been proved to be valuable in detecting myocardial ischemia. During quantitative MCE analysis, myocardial segmentation is a critical step in determining accurate region of interests (ROIs). However, traditional myocardial segmentation mainly relies on manual tracing of myocardial contours, which is time-consuming and laborious. To solve this problem, we propose a fully automatic myocardial segmentation framework that can segment myocardial regions in MCE accurately without human intervention. A total of 100 patients' MCE sequences were divided into a training set and a test set according to a 7: 3 proportion for analysis. We proposed a bi-directional training schema, which incorporated temporal information of forward and backward direction among frames in MCE sequences to ensure temporal consistency by combining convolutional neural network with recurrent neural network. Experiment results demonstrated that compared with a traditional segmentation model (U-net) and the model considering only forward temporal information (U-net + forward), our framework achieved the highest segmentation precision in Dice coefficient (U-net vs U-net + forward vs our framework: 0.78 ± 0.07 vs 0.79 ± 0.07 vs 0.81 ± 0.07, p < 0.01), Intersection over Union (0.65 ± 0.09 vs 0.66 ± 0.09 vs 0.68 ± 0.09, p < 0.01), and lowest Hausdorff Distance (32.68 ± 14.6 vs 28.69 ± 13.18 vs 27.59 ± 12.82 pixel point, p < 0.01). In the visual grading study, the performance of our framework was the best among these three models (52.47 ± 4.29 vs 54.53 ± 5.10 vs 57.30 ± 4.73, p < 0.01). A case report on a randomly selected subject for perfusion analysis showed that the perfusion parameters generated by using myocardial segmentation of our proposed framework were similar to that of the expert annotation. The proposed framework could generate more precise myocardial segmentation when compared with traditional methods. The perfusion parameters generated by these myocardial segmentations have a good similarity to that of manual annotation, suggesting that it has the potential to be utilized in routine clinical practice.

2.
Waste Manag ; 124: 94-101, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33611158

RESUMO

How to realize the high value-added utilization of scrap copper from e-waste is a meaningful topic. In the study, an Ohno Continuous Casting (OCC) process is an existing method you applied to purify the copper. Based onthe model of diffusion-controlled grain growth kinetics, the redistribution of impurity of tin in the scrap copper were studied under the different continuous casting speed and mold temperature. On the centerline, macrosegregation in the axial direction of the tin was more obvious with the decrease of continuous casting speed. The small continuous casting rate was beneficial to the segregation and enrichment of tin. The axial segregation gradually decreased with the increase of the mold temperature. The flattening of the liquid-solid interface resulted in a weakening of the solute enrichment at the root of the interface with the increase of temperature. Morphology, electron backscattered diffraction (EBSD) analysis showed the structure of single crystal copper. The range of resistance of single crystal copper was from 5 × 10-6 to 3 × 10-5 Ω m. Obviously, the resistance of the single crystal copper was significantly smaller than that of ordinary copper wire (9.0 × 10-3 Ω m). This study provided a key theoretical and practical basis for the high value-added reuse of copper in e-waste.

3.
Nat Med ; 27(2): 301-309, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33558722

RESUMO

The association among pathological response, recurrence-free survival (RFS) and overall survival (OS) with neoadjuvant therapy in melanoma remains unclear. In this study, we pooled data from six clinical trials of anti-PD-1-based immunotherapy or BRAF/MEK targeted therapy. In total, 192 patients were included; 141 received immunotherapy (104, combination of ipilimumab and nivolumab; 37, anti-PD-1 monotherapy), and 51 received targeted therapy. A pathological complete response (pCR) occurred in 40% of patients: 47% with targeted therapy and 33% with immunotherapy (43% combination and 20% monotherapy). pCR correlated with improved RFS (pCR 2-year 89% versus no pCR 50%, P < 0.001) and OS (pCR 2-year OS 95% versus no pCR 83%, P = 0.027). In patients with pCR, near pCR or partial pathological response with immunotherapy, very few relapses were seen (2-year RFS 96%), and, at this writing, no patient has died from melanoma, whereas, even with pCR from targeted therapy, the 2-year RFS was only 79%, and OS was only 91%. Pathological response should be an early surrogate endpoint for clinical trials and a new benchmark for development and approval in melanoma.

4.
Nat Commun ; 12(1): 346, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436641

RESUMO

Anti-PD-1 therapy is used as a front-line treatment for many cancers, but mechanistic insight into this therapy resistance is still lacking. Here we generate a humanized (Hu)-mouse melanoma model by injecting fetal liver-derived CD34+ cells and implanting autologous thymus in immune-deficient NOD-scid IL2Rγnull (NSG) mice. Reconstituted Hu-mice are challenged with HLA-matched melanomas and treated with anti-PD-1, which results in restricted tumor growth but not complete regression. Tumor RNA-seq, multiplexed imaging and immunohistology staining show high expression of chemokines, as well as recruitment of FOXP3+ Treg and mast cells, in selective tumor regions. Reduced HLA-class I expression and CD8+/Granz B+ T cells homeostasis are observed in tumor regions where FOXP3+ Treg and mast cells co-localize, with such features associated with resistance to anti-PD-1 treatment. Combining anti-PD-1 with sunitinib or imatinib results in the depletion of mast cells and complete regression of tumors. Our results thus implicate mast cell depletion for improving the efficacy of anti-PD-1 therapy.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Linfócitos do Interstício Tumoral/imunologia , Mastócitos/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Animais , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Mastócitos/efeitos dos fármacos , Melanoma/imunologia , Melanoma/patologia , Melanoma/terapia , Camundongos Transgênicos , Receptor de Morte Celular Programada 1/metabolismo , Sunitinibe/farmacologia , Sunitinibe/uso terapêutico , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
5.
Gut ; 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431576

RESUMO

OBJECTIVE: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) pathophysiology remains unclear. This study aims to characterise the molecular basis of HBV-ACLF using transcriptomics. METHODS: Four hundred subjects with HBV-ACLF, acute-on-chronic hepatic dysfunction (ACHD), liver cirrhosis (LC) or chronic hepatitis B (CHB) and normal controls (NC) from a prospective multicentre cohort were studied, and 65 subjects (ACLF, 20; ACHD, 10; LC, 10; CHB, 10; NC, 15) among them underwent mRNA sequencing using peripheral blood mononuclear cells (PBMCs). RESULTS: The functional synergy analysis focusing on seven bioprocesses related to the PBMC response and the top 500 differentially expressed genes (DEGs) showed that viral processes were associated with all disease stages. Immune dysregulation, as the most prominent change and disorder triggered by HBV exacerbation, drove CHB or LC to ACHD and ACLF. Metabolic disruption was significant in ACHD and severe in ACLF. The analysis of 62 overlapping DEGs further linked the HBV-based immune-metabolism disorder to ACLF progression. The signatures of interferon-related, neutrophil-related and monocyte-related pathways related to the innate immune response were significantly upregulated. Signatures linked to the adaptive immune response were downregulated. Disruptions of lipid and fatty acid metabolism were observed during ACLF development. External validation of four DEGs underlying the aforementioned molecular mechanism in patients and experimental rats confirmed their specificity and potential as biomarkers for HBV-ACLF pathogenesis. CONCLUSIONS: This study highlights immune-metabolism disorder triggered by HBV exacerbation as a potential mechanism of HBV-ACLF and may indicate a novel diagnostic and treatment target to reduce HBV-ACLF-related mortality.

6.
Am J Dermatopathol ; 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33464752

RESUMO

ABSTRACT: The synchronous incidence of 2 different subtypes of melanoma is very rare. Desmoplastic melanoma (DM) can be a diagnostic challenge because of its frequent appearance as a dermal banal spindle cell proliferation. We present a case of a 30-year-old man who developed an irregular, purple, tender plaque measuring 2.5 cm on the right pretibial region. Wide excision of the right leg lesion showed superficial spreading melanoma with epithelioid cells and no spindle cell component. Sentinel lymph node (SLN) biopsy showed an atypical melanocytic proliferation involving one inguinal lymph node with subcapsular and intraparenchymal components. There were spindled tumor cells in lymph node capsule with hyperchromatic nuclei, which were nested within desmoplastic stroma, and were S100- and SOX10-positive and MART1- and HMB-45 negative; in addition to epithelioid tumor cells, which were S100-, SOX10-, and MART1-positive. Multiple discontinuous foci, subcapsular atypical melanocytes, and extracapsular extension helped in excluding capsular nevus. These findings were consistent with DM. Herein, we present an unusual case of primary cutaneous superficial spreading melanoma of the right leg with a predominantly epithelioid morphology that developed metastases to the SLN. The metastasis exhibited divergent differentiation, including both epithelioid morphology identical to the primary, but with additional features of DM that were nonoverlapping with the primary lesion.

7.
Biomater Sci ; 9(4): 1246-1255, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33367372

RESUMO

Organ transplantation has been employed upon serious injuries, but a T-cell-mediated potent inflammatory immune response often leads to graft rejection. Immunosuppressive drugs such as rapamycin (RAPA) have to be taken after organ transplantation, but long-term use of these drugs causes severe adverse effects. Immune checkpoint pathways such as the programmed death-receptor 1/programmed death-ligand 1 (PD-1/PD-L1) provides an immunosuppressive environment, preventing excessive tissue destruction due to inflammatory immune responses. In this study, we bioengineered cell membrane-derived PD-L1 nanovesicles (PD-L1 NVs) to carry low doses of RAPA. These NVs inhibited T-cell activation and proliferation in vitro, by enhancing the PD-1/PD-L1 immune co-inhibitory signaling axis and inhibiting the mTOR pathway. Importantly, PD-L1 NVs encapsulated with rapamycin exerted stronger effects on inhibiting T-cell proliferation than PD-L1 NVs or rapamycin alone. This can be recapitulated in a mouse skin transplantation model, leading to the weakened alloimmune response and allograft tolerance. We also found that PD-L1/rapamycin vesicles have additional function to induce regulatory T cells in the recipient spleens. Our study highlighted the power of combining low-dose rapamycin and PD-L1 in the nanovesicles as immunosuppressants to promote allograft acceptance.

8.
Cell Rep ; 33(13): 108571, 2020 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-33378668

RESUMO

Here, we report that functional heterogeneity of macrophages in cancer could be determined by the nature of their precursors: monocytes (Mons) and monocytic myeloid-derived suppressor cells (M-MDSCs). Macrophages that are differentiated from M-MDSCs, but not from Mons, are immune suppressive, with a genomic profile matching that of M-MDSCs. Immune-suppressive activity of M-MDSC-derived macrophages is dependent on the persistent expression of S100A9 protein in these cells. S100A9 also promotes M2 polarization of macrophages. Tissue-resident- and Mon-derived macrophages lack expression of this protein. S100A9-dependent immune-suppressive activity of macrophages involves transcription factor C/EBPß. The presence of S100A9-positive macrophages in tumor tissues is associated with shorter survival in patients with head and neck cancer and poor response to PD-1 antibody treatment in patients with metastatic melanoma. Thus, this study reveals the pathway of the development of immune-suppressive macrophages and suggests an approach to their selective targeting.

9.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(11): 1241-1243, 2020 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-33179229

RESUMO

OBJECTIVE: To analyze the molecular etiology of a Chinese child affected with dihydropyrimidinase deficiency. METHODS: Genomic DNA was extracted from peripheral blood samples of the family members. Pathogenic variant was determined by whole exome sequencing and verified by Sanger sequencing. RESULTS: The child was found to harbor homozygous c.905G>A (p.Arg302Gln) variants in exon 5 of the DPYS gene, for which her parents were both heterozygous carriers. CONCLUSION: The homozygous c.905G>A (p.Arg302Gln) variants of the DPYS gene probably underlies the dihydropyrimidinase deficiency in the child. Above result has enabled genetic counseling and prenatal diagnosis for this family.


Assuntos
Amidoidrolases/genética , Erros Inatos do Metabolismo/genética , Grupo com Ancestrais do Continente Asiático/genética , Criança , Éxons , Feminino , Humanos , Mutação , Linhagem
10.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(5): 603-608, 2020 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-33210487

RESUMO

OBJECTIVE: To establish reuse process of positive pressure powered air-filter protective hoods during coronavirus disease 2019 (COVID-19) epidemic. METHODS: The procedure of pretreatment, storage, recovery, cleaning, disinfection and sterilization process of positive pressure powered air-filter protective hoods, which were used in the treatment of COVID-19 infection patients was established in Central Sterile Supply Department of the hospital. The cleaning and disinfection effects of the protective hoods after treatment were examined by magnifying glass method, residual protein detection method, real-time PCR, and agar pour plate method. RESULTS: Twenty five used protective hoods underwent totally 135 times of washing, disinfecting and sterilizing procedures. After washing, all the protein residue tests and COVID-19 nucleic acid tests showed negative results. After sterilizing, all the protective hoods met sterility requirement. All the tested protective hoods were undamaged after reprocessing. CONCLUSIONS: The established reuse procedures for used positive pressure powered air-filter protective hoods are safe.


Assuntos
Filtros de Ar , Infecções por Coronavirus , Desinfecção , Reutilização de Equipamento , Pandemias , Pneumonia Viral , Esterilização , Filtros de Ar/normas , Filtros de Ar/virologia , Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Desinfecção/normas , Reutilização de Equipamento/normas , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Esterilização/normas
11.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(11): 1009-1015, 2020 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-33210595

RESUMO

Objective To investigate the role and mechanism of endothelin receptor antagonist CPU0213 in myocardial ischemia-reperfusion (I/R) injury and oxidative stress injury. Methods In order to investigate the role of CPU0213 in I/R, SD rats were randomly divided into sham operation group, ischemia reperfusion injury (I/R) group, CPU0213 treatment group after I/R, CPU0213 and Janus kinase 2 (JAK2) specific inhibitor AG490 treatment group after I/R. In order to investigate the role of CPU0213 in oxidative stress damage, the isolated and characterized cardiomyocytes were cultured and divided into control group, H2O2 oxidative stress group (H2O2 group), oxidative stress damaged group treated with CPU0213, and oxidative stress damaged group treated with CPU0213 and AG490. The rat myocardial I/R models were constructed, and the rats and cardiomyocytes were treated with different treatments according to the experimental requirements. The rat heart was stained with triphenyltetrazolium chloride (TTC) to observe the area of myocardial infarction and the lactate dehydrogenase (LDH) and creatine kinase (CK) activity, flow cytometry to detect the apoptosis rate of cardiomyocytes, CCK-8 method to detect cell growth viability, Western blotting to detect the expression of Bcl2, JAK2, phosphorylated JAK2 (p-JAK2), caspase-3 and caspase-9, STAT3 and phosphorylated STAT3 (p-STAT3). Results After I/R injury in mice, CPU0213 treatment reduced myocardial infarction area, LDH, CK activity and apoptosis rate, but increased the phosphorylation level of JAK2 and STAT3. Compared with I/R combined with CPU0213, I/R combined with CPU0213 and AG490 increased the expression of caspase-3 and caspase-9, decreased significantly the expression of Bcl2 and the cell viability. After oxidative stress damage to cardiomyocytes, CPU0213 treatment reduced LDH, CK activity and cell apoptosis rate, and increased the phosphorylation level of JAK2 and STAT3. In the oxidative stress damaged group treated with CPU0213 and AG490, caspase-3 and caspase-9 expression increased, Bcl2 expression dropped significantly, cell viability decreased significantly. Conclusion The activation of JAK2/STAT3 pathway by CPU0213 can inhibit the apoptosis of cardiomyocytes induced by I/R and oxidative stress.

13.
Clin Cancer Res ; 26(21): 5709-5719, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33097493

RESUMO

PURPOSE: Angiogenesis is thought to be critical for tumor metastasis. However, inhibiting angiogenesis using antibodies such as bevacizumab (Avastin), has had little impact on melanoma patient survival. We have demonstrated that both angiogenesis and metastasis are increased in older individuals, and therefore sought to investigate whether there was an age-related difference in response to bevacizumab, and if so, what the underlying mechanism could be. EXPERIMENTAL DESIGN: We analyzed data from the AVAST-M trial of 1,343 patients with melanoma treated with bevacizumab to determine whether there is an age-dependent response to bevacizumab. We also examined the age-dependent expression of VEGF and its cognate receptors in patients with melanoma, while using syngeneic melanoma animal models to target VEGF in young versus old mice. We also examined the age-related proangiogenic factor secreted frizzled-related protein 2 (sFRP2) and whether it could modulate response to anti-VEGF therapy. RESULTS: We show that older patients respond poorly to bevacizumab, whereas younger patients show improvement in both disease-free survival and overall survival. We find that targeting VEGF does not ablate angiogenesis in an aged mouse model, while sFRP2 promotes angiogenesis in vitro and in young mice. Targeting sFRP2 in aged mice successfully ablates angiogenesis, while the effects of targeting VEGF in young mice can be overcome by increasing sFRP2. CONCLUSIONS: VEGF is decreased during aging, thereby reducing response to bevacizumab. Despite the decrease in VEGF, angiogenesis is increased because of an increase in sFRP2 in the aged tumor microenvironment. These results stress the importance of considering age as a factor for designing targeted therapies.

14.
Polymers (Basel) ; 12(10)2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33086515

RESUMO

The mechanism of ethylene with vinyl ether (VE, CH2=CHOEt) copolymerization catalyzed by phosphine-sulfonate palladium complex (A) was investigated by density functional theory (DFT) calculation. On achieving an agreement between theory and experiment, it is found that the favorable 1,2-selective insertion of VE into the complex A originates from stronger hydrogen interaction between the oxygen atom of VE and the ancillary ligand of catalyst A. Additionally, VE insertion is easier into the ethylene pre-inserted intermediate than that into the catalyst to form the resultant copolymers with the major units of OEt in chain and minor units of OEt at the chain end. The effect of ß-OEt and ß-H elimination was explored to elucidate chain termination and the molecular weight of copolymers. Furthermore, a family of cationic catalysts has been demonstrated to copolymerize ethylene with VE along with our modified cationic complex B with higher incorporation of VE and reactivity in comparison with complex A, which was modelled computationally by increasing the strong interactions between the catalyst and monomer moiety. Other than VE, the activity of cationic complex B for copolymerization of vinyl chloride and methacrylate is also computed successfully.

15.
ACS Appl Mater Interfaces ; 12(45): 50287-50302, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33121247

RESUMO

Nucleic acid transfer has shown significant potential in the treatment of bone damage because of its long lasting local effect and lower cost. Nonviral vectors, such as nanomaterials, with higher biocompatibility are increasedly applied in the study of bone defect repair. Carbon dots with various reactive groups on the surface not only provide a unique surface to carry therapeutic genes, but also some carbon dots have been reported to promote osteogenic differentiation. The bone regeneration effect of carbon dots in vivo, however, is rarely investigated. MiR-2861 has revealed osteogenic differentiation effects. In the current study, we created ascorbic acid-PEI carbon dots (CD), which were able to carry miR-2861, by the microwave-assisted pyrolysis method. Results demonstrated that CD had excellent fluorescence stability leading to good fluorescence imaging in vitro and in vivo. CD was efficiently internalized into bone marrow stromal cells (BMSCs) through the clathrin-mediated endocytosis pathway and distributed in the mitochondria, endoplasmic reticulum, lysosome, and nucleus. Results from alkaline phosphatase staining, alizarin red staining, and reverse transcription real-time PCR (RT-QPCR) showed that our CD indeed had osteogenic effects in vitro. Flow cytometry data indicated that CD could efficiently deliver miR-2861 into BMSCs in vitro, and CD carrying miR-2861 (CD@miR) had the strongest osteogenic effects. Analyses of hematology, serum biochemistry, and histology showed that CD and CD@miR did not have cytotoxicity and had higher biocompatibility in vivo. Most interestingly, CD and miR-2861 in the CD@miR could act synergistically to promote osteogenic differentiation in vitro and new bone regeneration in vivo remarkably. Our results clearly indicate that the osteogenic CD delivering osteogenic therapeutic gene, miR-2861, can obtain much stronger bone regeneration ability, suggesting that our CD has great potential in future clinical application.

16.
Front Chem ; 8: 756, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33005608

RESUMO

Human NAD(P)H: quinone oxidoreductase (hNQO1) is an important biomarker for human malignant tumors. Detection of NQO1 accurately is of great significance to improve the early diagnosis of cancer and prognosis of cancer patients. In this study, based on the covalent assembly strategy, hNQO1-activated fluorescent probes 1 and 2 are constructed by introducing coumarin precursor 2-cyano-3-(4-(diethylamino)-2-hydroxyphenyl) acrylic acid and self-immolative linkers. Under reaction with hNQO1 and NADH, turn-on fluorescence appears due to in-situ formation of the organic fluorescent compound 7-diethylamino-3-cyanocoumarin, and fluorescent intensity changes significantly. Probe 1 and 2 for detection of hNQO1 are not interfered by other substances and have low toxicity in cells. In addition to quantitative detection of hNQO1 in vitro, they have also been successfully applied to fluorescent imaging in living cells.

17.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 1372-1375, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018244

RESUMO

Classification of normal lung tissue, lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) by pathological images is significant for clinical diagnosis and treatment. Due to the large scale of pathological images and the absence of definitive morphological features between LUAD and LUSC, it is time-consuming, laborious and challenging for pathologists to analyze the microscopic histopathology slides by visual observation. In this paper, a pixel-level annotation-free framework was proposed to classify normal tissue, LUAD and LUSC slides. This framework can be divided into two stages: tumor classification and localization, and subtype classification. In the first stage, EM-CNN was utilized to distinguish tumor slides from normal tissue slides and locate the discriminative regions for subsequent analysis with only image-level labels provided. In the second stage, a multi-scale network was proposed to improve the accuracy of subtype classification. This method achieved an AUC of 0.9978 for tumor classification and an AUC of 0.9684 for subtype classification, showing its superiority in lung pathological image classification compared with other methods.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Carcinoma de Células Escamosas/diagnóstico , Humanos , Patologistas
18.
Sci Rep ; 10(1): 18128, 2020 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-33093629

RESUMO

Increased oxidative stress levels play a key role in idiosyncratic drug-induced liver injury (DILI) pathogenesis. To investigated whether advanced oxidation protein products (AOPPs) and ischaemia-modified albumin (IMA) can be used to monitor oxidative stress in DILI patients and to assess disease severity. We performed spectrophotometric assays to assess AOPPs and IMA in 68 DILI patients with severity grade 0-2 (non-severe group), 60 with severity grade 3-5 (severe group), and 38 healthy controls. The results showed that baseline AOPPs and IMA serum levels and AOPPs/albumin and IMA/albumin ratios were significantly higher in DILI patients than in healthy controls. Besides, in comparison to the non-severe group, the severe group showed higher baseline AOPPs and IMA serum levels and AOPPs/albumin and IMA/albumin ratios. AOPPs and IMA serum levels and AOPPs/albumin and IMA/albumin ratios decreased after treatment in both patient groups. Combining the correlation analysis and areas under the receiver operating curve (AUROCs) analysis results, that IMA outperformed to be one is the most reliable marker to assess disease severity of DILI. Our findings indicated that AOPPs and IMA can serve as key biomarkers for monitoring oxidative stress levels in DILI patients and can indicate disease severity. The IMA outperformed to be one of the most reliable oxidative stress biomarkers to assess disease severity of DILI.

20.
Mol Genet Genomic Med ; 8(11): e1501, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32959514

RESUMO

BACKGROUND: 21-Hydroxylase deficiency (21-OHD) caused by the CYP21A2 gene mutations is the most common form of congenital adrenal hyperplasia. It is an autosomal recessive disorder that results in defective synthesis of cortisol and aldosterone. The incidences of various CYP21A2 gene mutations and the genotype-phenotype correlations vary among different populations. MATERIALS AND METHODS: The clinical and molecular data of 22 patients were analyzed in this study. All patients were recruited from the neonatal intensive care unit. Locus-specific polymerase chain reaction and Sanger sequencing were applied to identify gene micro-conversions, and multiplex ligation-dependent probe amplification was used to detect large fragment deletions/conversions. Then, the genotypes were categorized in to Null, A, B, C, and D groups to analyze the relationships between genotypes and phenotypes. RESULTS: All 22 patients were classified into classic salt wasting form of 21-OHD. Molecular defects were detected in 44 alleles (100%). Micro-conversion mutation IVS2-13A/C>G (70.5%) is most common in our cohort, followed by large gene deletions and conversions (22.7%). The other mutations present were p.R357 W (4.5%) and E6 Cluster (2.3%). Genotypes of 22 patients (100%) were consistent with the predictive phenotypes. CONCLUSION: In this study, we identified the mutation spectrum of CYP21A2 gene in Chinese patients, especially the younger age cohort in pediatrics. Micro-conversions were the most popular mutations. Moreover, the genotypes and phenotypes were well correlated in this cohort of salt wasting 21-OHD recruited from neonatal intensive care unit.

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