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1.
Eur Radiol ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834788

RESUMO

OBJECTIVES: To investigate the potential utility of [18F]fibroblast activation protein inhibitor (FAPI) positron emission tomography/computed tomography (PET/CT) for evaluating pulmonary artery (PA) masses, and compare it with [18F]fluorodeoxyglucose (FDG) PET/CT. METHODS: Participants with clinically suspected PA malignancy were prospectively enrolled and underwent dual-tracer PET/CT ([18F]FAPI-42 and [18F]FDG) imaging. Visual analysis and semi-quantitative parameters were compared between the two types of radiotracers. The tissue specimen underwent immunohistochemical staining to verify FAP expression in the tissue. RESULTS: Thirty-three patients (18 males/15 females; mean age 53.1 ± 15.4 years) were enrolled. All 21 patients with malignant PA masses were FDG-positive (100%), whereas 20 out of 21 patients were FAPI-positive (95.2%). All 12 patients with benign PA masses were both negative in FDG and FAPI PET. The mean maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR) of FAPI and FDG in malignant PA masses were significantly higher than those of benign masses. Although there was no significant difference in SUVmax between FDG and FAPI in malignant PA masses (11.36 vs. 9.18, p = 0.175), the TBR (liver) and TBR (left ventricle) were more favorable for FAPI than for FDG (13.04 vs. 5.17, p < 0.001); (median: 7.75 vs. 2.75, p = 0.007). Immunohistochemical analysis (n = 16) validated that the level of FAP expression corresponded strongly to the uptake of FAPI in PET/CT scans (rs = 0.712, p = 0.002). For clinical management, FAPI PET found more metastatic lesions than FDG PET in 4 patients, with 2 patients upgrading and 1 patient changing treatment decisions. CONCLUSIONS: FAPI PET/CT is feasible in the diagnosis of PA masses. Although not superior to FDG PET/CT, FAPI PET/CT showed better target-to-background contrast. CLINICAL RELEVANCE STATEMENT: This study found that FAPI PET/CT is not superior to FDG PET/CT in diagnosing PA masses, but FAPI PET/CT displays better target-to-background contrast and more positive lesions, which may help improve disease management. KEY POINTS: Pulmonary malignancies lack specificity in clinical manifestations, laboratory tests, and routine imaging examinations. FAPI PET/CT is not diagnostically better than FDG PET/CT but displays better target-to-background contrast and more positive lesions. Dual-tracer PET/CT ([18F]FAPI-42 and [18F]FDG) imaging improves clinical management of pulmonary artery masses.

2.
Front Microbiol ; 15: 1380322, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38784814

RESUMO

The establishment of the rumen microbiota plays an important role in the rumen development. However, little is known about the effects of alfalfa supplementation time on rumen microbiota establishment. Here, a total of 42 Hu lambs, seven-day-old, were chosen for the study. After a week of adjustment, six lambs were sacrificed to establish a baseline. The remaining 36 lambs were randomly split into two groups: one receiving alfalfa hay at 14 days (EAF), the other at 42 days (LAF), both groups received milk replacer and starter pellets. Introducing alfalfa at 14 days of age significantly improved total dry matter intake between 28 and 42 days (p = 0.04) and average daily gain from both 14 to 28 days (p = 0.04) and 28 to 42 days (p < 0.01), but this effect disappears from 56 to 70 days (p > 0.05). At 42 days, the abundances of Naganishia, Ascochyta, and Neosetophoma in the EAF group were significantly higher (p < 0.05) than those in the LAF group (17.8% vs. 3.97, 10.89% vs. 1.77, and 1.27% vs. 0.09%, respectively). At 56 days, the abundances of Ascochyta, Wallemia, and Aspergillus in the EAF group were significantly lower (p < 0.05) than in the LAF group (3.53% vs. 16.40, 8.78% vs. 18.89, and 2.14% vs. 4.69%). At 70 days, Aspergillus abundance in the EAF group was significantly higher (p < 0.05) than in the LAF group (2.69% vs. 0.85%). The LEfSe analysis showed that Methanobrevibacter_smithii was the archaeal biomarker at 14 days in both groups. Methanobrevibacter_sp_AbM4 was enriched at 56 days in the LAF group. Compared to the LAF group, the specific fungal biomarkers in the EAF group included Sporobolomyces and Bullera at 14 days, Naganishia, Didymella, Cleistothelebolus, and Alloleptosphaeria at 42 days, Ascochyta, Neoascochyta, and Alfaria at 70 days. Correlation analysis results showed strong patterns of association both within and between archaea and fungi, which were influenced by alfalfa supplementation time. In summary, alfalfa supplementation at 14 days of age promotes the growth performance of lambs before weaning, and alfalfa supplementation timing significantly affects rumen archaeal and fungal communities and dynamical changes.

3.
Aging (Albany NY) ; 16(6): 5123-5148, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38498906

RESUMO

The Hedgehog (Hh) signaling pathway has been implicated in the pathogenesis of various cancers. However, the roles of the downstream GLI family (GLI1, GLI2, and GLI3) in tumorigenesis remain elusive. This study aimed to unravel the genetic alterations of GLI1/2/3 in cancer and their association with the immune microenvironment and related signaling pathways. Firstly, we evaluated the expression profiles of GLI1/2/3 in different cancer types, analyzed their prognostic and predictive values, and assessed their correlation with tumor-infiltrating immune cells. Secondly, we explored the relationships between GLI1/2/3 and genetic mutations, epigenetic modifications, and clinically relevant drugs. Finally, we performed enrichment analysis to decipher the underlying mechanisms of GLI1/2/3 in cancer initiation and progression. Our results revealed that the expression levels of GLI1/2/3 were positively correlated in most cancer tissues, suggesting a cooperative role of these factors in tumorigenesis. We also identified tissue-specific expression patterns of GLI1/2/3, which may reflect the distinct functions of these factors in different cell types. Furthermore, GLI1/2/3 expression displayed significant associations with poor prognosis in several cancers, indicating their potential as prognostic biomarkers and therapeutic targets. Importantly, we found that GLI1/2/3 modulated the immune microenvironment by regulating the recruitment, activation, and polarization of cancer-associated fibroblasts, endothelial cells, and macrophages. Additionally, functional enrichment analyses indicated that GLI1/2/3 are involved in the regulation of epithelial-mesenchymal transition (EMT). Together, our findings shed new light on the roles of GLI1/2/3 in tumorigenesis and provide a potential basis for the development of novel therapeutic strategies targeting GLI-mediated signaling pathways in cancer.


Assuntos
Neoplasias , Fatores de Transcrição , Humanos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteína GLI1 em Dedos de Zinco/genética , Células Endoteliais/metabolismo , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Neoplasias/genética , Prognóstico , Carcinogênese , Análise de Célula Única , Microambiente Tumoral/genética
4.
Front Genet ; 15: 1255455, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38444758

RESUMO

Purpose: Osteoarthritis (OA) is a disease of senescence and inflammation. Hedgehog's role in OA mechanisms is unclear. This study combines Bulk RNA-seq and scRNA-seq to identify Hedgehog-associated genes in OA, investigating their impact on the pathogenesis of OA. Materials and methods: Download and merge eight bulk-RNA seq datasets from GEO, also obtain a scRNA-seq dataset for validation and analysis. Analyze Hedgehog pathway activity in OA using bulk-RNA seq datasets. Use ten machine learning algorithms to identify important Hedgehog-associated genes, validate predictive models. Perform GSEA to investigate functional implications of identified Hedgehog-associated genes. Assess immune infiltration in OA using Cibersort and MCP-counter algorithms. Utilize ConsensusClusterPlus package to identify Hedgehog-related subgroups. Conduct WGCNA to identify key modules enriched based on Hedgehog-related subgroups. Characterization of genes by methylation and GWAS analysis. Evaluate Hedgehog pathway activity, expression of hub genes, pseudotime, and cell communication, in OA chondrocytes using scRNA-seq dataset. Validate Hedgehog-associated gene expression levels through Real-time PCR analysis. Results: The activity of the Hedgehog pathway is significantly enhanced in OA. Additionally, nine important Hedgehog-associated genes have been identified, and the predictive models built using these genes demonstrate strong predictive capabilities. GSEA analysis indicates a significant positive correlation between all seven important Hedgehog-associated genes and lysosomes. Consensus clustering reveals the presence of two hedgehog-related subgroups. In Cluster 1, Hedgehog pathway activity is significantly upregulated and associated with inflammatory pathways. WGCNA identifies that genes in the blue module are most significantly correlated with Cluster 1 and Cluster 2, as well as being involved in extracellular matrix and collagen-related pathways. Single-cell analysis confirms the significant upregulation of the Hedgehog pathway in OA, along with expression changes observed in 5 genes during putative temporal progression. Cell communication analysis suggests an association between low-scoring chondrocytes and macrophages. Conclusion: The Hedgehog pathway is significantly activated in OA and is associated with the extracellular matrix and collagen proteins. It plays a role in regulating immune cells and immune responses.

5.
J Thorac Dis ; 16(1): 51-64, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38410615

RESUMO

Background: Transthoracic echocardiography (TTE) is recommended as the most important noninvasive screening tool for the diagnosis of pulmonary hypertension (PH), sonographers usually measure the volume of regurgitant flow rather than evaluating the spectral quality, so physicians will determine whether the ultrasound measurements of pulmonary arterial systolic pressure (US-PASP) are reliable based on the volume of tricuspid regurgitation (TR). Therefore, for the first time, we grade the quality of TR spectrum (TRS) based on its integrity and clarity, aiming to assess clinical application value of different tricuspid regurgitant spectrum quality grades (TR-SQG), and investigate whether the accuracy of US-PASP is more trustworthy than TR. Methods: We retrospectively analyzed 108 patients with chronic thromboembolic PH (CTEPH) to compare the correlation and agreement between US-PASP and right heart catheterization measurements of PASP (RHC-PASP). TR area (TRA) and TRS were measured in each patient, and TR-SQG was performed. Results: The correlation coefficients between US-PASP and RHC-PASP were r=0.622 (P<0.001), r=0.754 (P<0.001), r=0.595 (P<0.001) in mild, moderate, severe TR, and r=0.301 (P=0.135), r=0.747 (P<0.001), r=0.739 (P<0.001), r=0.828 (P<0.001) in TR-SQG I-IV, respectively. Bland-Altman analysis revealed the mean biases of 5.05, 3.06, 7.62 mmHg in mild, moderate, severe TR, and -16.47, -8.07, 1.82, 6.09 mmHg in TR-SQG I-IV, respectively. In mild TR with the TR-SQG III and IV, the correlation coefficients between US-PASP and RHC-PASP were r=0.779 (P<0.001), intraclass correlation coefficient (ICC) =0.774, paired t-test P=0.160, respectively; and the consistency was significantly higher than that of mild TR without considering TR-SQG. In moderate TR with the TR-SQG III and IV, the r=0.749, ICC =0.746, paired t-test P=0.298 between US-PASP and RHC-PASP. Conclusions: The US-PASP with TR-SQG III or IV is trustworthy, and its accuracy and consistency are better than those predicted by the traditional severity of TR. The establishment of the ultrasound evaluation system of TR-SQG helps clinicians to judge whether the US-PASP is accurate, credible, and reliable.

6.
Animals (Basel) ; 14(3)2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38338161

RESUMO

Cold conditions in northern China during winter may reduce sheep growth and affect their health, especially if they are young, unless housing is provided. We allocated 45 two-month-old female lambs to be housed in an enclosed building, a polytunnel, or kept outdoors, for 28 days. The daily weight gain and scalp and ear skin temperature of outdoor lambs were less than those of lambs that were housed in either a house or polytunnel; however, rectal temperature was unaffected by treatment. There was a progressive change in blood composition over time, and by the end of the experiment, outdoor lambs had reduced total antioxidant capacity (T-AOC), catalase (CAT), glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD) and increased malondialdehyde compared to those in the house or polytunnel. In relation to immune responses in the lambs' serum, in the polytunnel, immunoglobulin A (IgA), tumor necrosis factor-α (TNF-α) and interleukin-4 (IL-4) were higher and immunoglobulin G (IgG) lower compared with the concentrations in lambs that were outdoors. Over the course of the experiment, genes expressing heat shock proteins and antioxidant enzymes increased in lambs in the outdoor treatment, whereas they decreased in lambs in the indoor treatments. It is concluded that although there were no treatment effects on core body temperature, the trends for progressive changes in blood composition and gene expression indicate that the outdoor lambs were not physiologically stable; hence, they should not be kept outdoors in these environmental conditions for long periods.

7.
Aging (Albany NY) ; 16(1): 129-152, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38175686

RESUMO

Lymphotoxin beta receptor (LTBR) is a positive T cell proliferation regulator gene. It is closely associated with the tumor immune microenvironment. However, its role in cancer and immunotherapy is unclear. Firstly, the expression level and prognostic value of LTBR were analyzed. Secondly, the expression of LTBR in clinical stages, immune subtypes, and molecular subtypes was analyzed. The correlation between LTBR and immune regulatory genes, immune checkpoint genes, and RNA modification genes was then analyzed. Correlations between LTBR and immune cells, scores, cancer-related functional status, tumor stemness index, mismatch repair (MMR) genes, and DNA methyltransferase were also analyzed. In addition, we analyzed the role of LTBR in DNA methylation, mutational status, tumor mutation burden (TMB), and microsatellite instability (MSI). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to explore the role of LTBR in pan-cancer. Finally, the drugs associated with LTBR were analyzed. The expression of LTBR was confirmed using quantitative real-time PCR and Western blot. LTBR is significantly overexpressed in most cancers and is associated with low patient survival. In addition, LTBR expression was strongly correlated with immune cells, score, cancer-related functional status, tumor stemness index, MMR genes, DNA methyltransferase, DNA methylation, mutational status, TMB, and MSI. Enrichment analysis revealed that LTBR was associated with apoptosis, necroptosis, and immune-related pathways. Finally, multiple drugs targeting LTBR were identified. LTBR is overexpressed in several tumors and is associated with a poor prognosis. It is related to immune-related genes and immune cell infiltration.


Assuntos
Receptor beta de Linfotoxina , Neoplasias , Humanos , Prognóstico , Metilases de Modificação do DNA , Instabilidade de Microssatélites , Neoplasias/genética , DNA , Microambiente Tumoral/genética
8.
Ther Adv Respir Dis ; 17: 17534666231212307, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38049958

RESUMO

BACKGROUND: Little is known about immediate responses of blood perfusion to the balloon pulmonary angioplasty (BPA) procedure. OBJECTIVES: To investigate the changes in pulmonary perfusion of balloon-dilated vessels and untreated vessels with before, immediately after a single BPA and at follow-up. DESIGN: Retrospective single-center cohort study. METHODS: Patients who had chronic thromboembolic pulmonary hypertension (CTEPH) and completed the pulmonary perfusion single photon emission computed tomography (SPECT) imaging before, immediately after BPA and at follow-up were included. We evaluated the perfusion defects of both-lung, BPA target (balloon dilated) and non-target (untreated) vessel segments according to Begic 3-point scale in each lung segment. RESULTS: Forty patients (40 BPA procedures) were included and were given next BPA after 89 (62-125) days. The hemodynamic parameters including mPAP, PVR, and RAP were significantly improved after a single BPA. Visual scoring results of pulmonary perfusion imaging in 40 BPAs showed the perfusion defect scores of target vessels reduced from 5.6 ± 2.6 to 4.2 ± 2.2 (p < 0.001) immediately after BPA, and then further diminished to 3.1 ± 1.9 (p < 0.001) at follow-up. While in the non-target vessels, the post-BPA perfusion defect scores did not change significantly (13.4 ± 4.7 versus 12.8 ± 4.6, p = 0.182), but tended to decrease at follow-up (12.2 ± 4.2). However, there were 17 BPAs of which the post-BPA perfusion defect scores of non-target vessels increased significantly (p < 0.001), but decreased at follow-up. CONCLUSION: In addition to improving the blood perfusion of target vessels, BPA also has a certain effect on the perfusion of some non-target vessels.


Assuntos
Angioplastia com Balão , Hipertensão Pulmonar , Embolia Pulmonar , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/terapia , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/terapia , Estudos Retrospectivos , Estudos de Coortes , Doença Crônica , Pulmão/diagnóstico por imagem , Angioplastia com Balão/efeitos adversos , Angioplastia com Balão/métodos , Perfusão , Artéria Pulmonar/diagnóstico por imagem
9.
Front Genet ; 14: 1204421, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37287535

RESUMO

[This corrects the article DOI: 10.3389/fgene.2023.1045061.].

10.
Pulm Circ ; 13(2): e12234, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37168839

RESUMO

Percutaneous endovascular biopsy (PEB) including forceps biopsy and catheter aspiration has been used to make a pretreatment diagnosis for pulmonary artery (PA) masses. This retrospective study aims to describe the procedure of PEB and compare the diagnostic yield of forceps biopsy and catheter aspiration for a definite diagnosis in patients with PA masses. All consecutive 22 patients (53 ± 14 years), 11 males and 11 females, who underwent PEB for pathologic confirmation between November 2018 and November 2022 were enrolled. All 22 patients performed computed tomography pulmonary angiography or positron emission tomography-computed tomography to confirm the filling defects suspicious for PA malignancy before intervention. And then, all patients underwent PEB successfully without acute or fatal complications, including both forceps biopsy and catheter aspiration in 15 cases, only forceps biopsy in 5 cases, and only catheter aspiration in 2 cases. Histopathological analysis provided a definite diagnosis in all PEBs with a clinical success of 91.0% (20/22). Among them, in 15 patients who underwent both forceps biopsy and aspiration biopsy, the technical success using forceps biopsy was 93.3% (14/15), and aspiration biopsy was 6.7% (1/15), and there was a significant difference in diagnostic accuracy when comparing two techniques. Twenty-one out of 22 PA masses (95.5%) were malignant, of which, the most frequent malignant lesion observed was PA sarcoma (66.7%, 14/21). Benign lesion included one thrombus (4.5%, 1/22). In conclusion, PEB is an effective and safe diagnostic method for differentiating benign and malignant PA masses and could be peformed when PA masses appeared clinically malignant.

11.
Clin Respir J ; 17(6): 536-547, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37141914

RESUMO

METHODS: The aetiological composition and clinical characteristics of patients with pulmonary hypertension (PH) hospitalised in the respiratory department were retrospectively analysed, as well as the correlation between transthoracic echocardiography (TTE) and right heart catheterization (RHC) for evaluating pulmonary artery systolic pressure (PASP) and mean pulmonary artery pressure (mPAP). RESULTS: Of 731 patients, 544 (74.42%) were diagnosed with PH by RHC. Pulmonary arterial hypertension (PAH) was the most common type of PH, accounting for 30.10%; PH due to lung disease and/or hypoxia accounted for 20.79%, and PH due to pulmonary artery obstructions accounted for 19.29%. TTE has the highest specificity for diagnosing PH due to pulmonary artery obstructions. The specificity was 0.9375, the sensitivity was 0.7361 and the area under the ROC curve (AUC) was 0.836. PASP, and mPAP estimated by TTE were different for various types of PH. In terms of PASP, TTE overestimated PASP in PH due to lung disease and/or hypoxia, but there was no significant difference compared with RHC (P > 0.05). TTE underestimates PAH patients' PASP compared with RHC. In terms of mPAP, TTE underestimated the mPAP of all types of PH, as there was a significant difference in the TTE-estimated mPAP of patients with PAH compared with RHC but not on other types of PH. Pearson correlation analysis of TTE and RHC showed a moderate overall correlation (rPASP 0.598, P < 0.001; rmPAP 0.588, P < 0.001). CONCLUSIONS: Among the patients with PH in the respiratory department, patients with PAH accounted for the majority. TTE has high sensitivity and specificity for the diagnosis of PH due to pulmonary artery obstructions in the respiratory department.


Assuntos
Hipertensão Pulmonar , Pneumopatias , Hipertensão Arterial Pulmonar , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/epidemiologia , Estudos Retrospectivos , Ecocardiografia , Artéria Pulmonar/diagnóstico por imagem , Pneumopatias/complicações , Hipertensão Pulmonar Primária Familiar/complicações , Cateterismo Cardíaco/efeitos adversos
12.
Front Genet ; 14: 1045061, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37035741

RESUMO

Purpose: Prolyl 4-hydroxylase subunit alpha 3 (P4HA3) is implicated in several cancers' development. However, P4HA3 has not been reported in other cancers, and the exact mechanism of action is currently unknown. Materials and methods: First, the expression profile of P4HA3 was analyzed using a combination of the University of California Santa Cruz (UCSC) database, Cancer Cell Line Encyclopedia (CCLE) database, and Genotype-Tissue Expression (GTEx) database. UniCox and Kaplan-Meier were used to analyze the predictive value of P4HA3. The expression of P4HA3 was analyzed in clinical staging, immune subtypes, and Molecular subtypes. Secondly, the correlation of P4HA3 with immunomodulatory genes, immune checkpoint genes, RNA modification genes, immune cell infiltration, cancer-related functional status, tumor stemness index, DNA mismatch repair (MMR) genes and DNA Methyltransferase was examined. The role of P4HA3 in DNA methylation, copy number variation (CNV), mutational status, tumor mutational burden (TMB), and microsatellite instability (MSI) was also analyzed. In addition, gene set enrichment analysis (GSEA) was used to explore the potential functional mechanisms of P4HA3 in pan-cancer. Finally, P4HA3-related drugs were searched in CellMiner, Genomics of Drug Sensitivity in Cancer (GDSC), and Cancer Therapeutics Response Portal (CTRP) databases. Results: P4HA3 is significantly overexpressed in most cancers and is associated with poor prognosis. P4HA3 is strongly associated with clinical cancer stage, immune subtypes, molecular subtypes, immune regulatory genes, immune checkpoint genes, RNA modifier genes, immune cell infiltration, cancer-related functional status, tumor stemness index, MMR Gene, DNA Methyltransferase, DNA methylation, CNV, mutational status, TMB, and MSI are closely related. Available enrichment analysis revealed that P4HA3 is associated with the epithelial-mesenchymal transition and immune-related pathways. There are currently 20 drugs associated with P4HA3. Conclusion: In human pan-cancer, P4HA3 is associated with poor patient prognosis and multiple immune cells and may be a novel immunotherapeutic target. It may act on tumor progression through the epithelial-mesenchymal transition (EMT) pathway.

13.
Stroke Vasc Neurol ; 8(4): 335-348, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36854487

RESUMO

Hyperhomocysteinemia (HHcy) is independently associated with poorer long-term prognosis in patients with intracerebral haemorrhage (ICH); however, the effect and mechanisms of HHcy on ICH are still unclear. Here, we evaluated neurite outgrowth and neurological functional recovery using simulated models of ICH with HHcy in vitro and in vivo. We found that the neurite outgrowth velocity and motor functional recovery in the ICH plus HHcy group were significantly slower than that in the control group, indicating that homocysteine (Hcy) significantly impedes the neurite outgrowth recovery after ICH. Furthermore, phosphoproteomic data and signalome analysis of perihematomal brain tissues suggested that calmodulin-dependent protein kinases 2 (CAMK2A) kinase substrate pairs were significantly downregulated in ICH with HHcy compared with autologous blood injection only, both western blot and immunofluorescence staining confirmed this finding. Additionally, upregulation of pCAMK2A significantly increased neurite outgrowth recovery in ICH with HHcy. Collectively, we clarify the mechanism of HHcy-hindered neurite outgrowth recovery, and pCAMK2A may serve as a therapeutic strategy for promoting neurological recovery after ICH.


Assuntos
Hemorragia Cerebral , Homocisteína , Humanos , Hemorragia Cerebral/complicações , Regulação para Cima , Crescimento Neuronal
14.
Medicine (Baltimore) ; 102(7): e32914, 2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-36800635

RESUMO

RATIONALE: Epithelioid hemangioendothelioma (EHE) is a rare, low to moderate-grade malignancy, even less in pulmonary endovascular neoplasm. Patients with pulmonary EHE have no optimal treatment, resulting in poor prognoses. PATIENT CONCERNS: We reported a 42-year-old man with multiple mild metabolic uptakes in pulmonary endovascular filling defect with a maximum standardized uptake value of 4.5 by 18-fluorodeoxyglucose/fibroblast associated protein inhibitor-positron emission tomography/ computed tomography. Anticoagulant treatment was not effective with the diagnosis of acute pulmonary embolism. DIAGNOSES: A primary endovascular EHE pulmonary endovascular epithelioid hemangioendothelioma was diagnosed by endovascular biopsy with positive stains for molecular CD31, CD34 and CAMTA1, and it had low proliferative capacity characterized by Ki-67 of 5%. The mutation gene MSH2 (p.Y656 in exon 12) (mutation abundance of 0.07%) from peripheral blood indicates the potential benefit of an immune checkpoint inhibitor, pembrolizumab. INTERVENTIONS AND OUTCOMES: The patient was treated with tri-weekly paclitaxel (175mg/m2) and carboplatin (AUC 5) chemotherapy regimen. He exerted a remarkable response after 5 cycles (21 days per cycle) and Pembrolizumab (200mg once monthly) as maintenance treatment. LESSONS: This case highlights the diagnostic challenge of differentiating endovascular lesions and optimal therapy for pulmonary EHE. Importantly, it indicated that the mutation gene MSH2 (p.Y656) might influence the pathogenesis of EHE.


Assuntos
Neoplasias Ósseas , Hemangioendotelioma Epitelioide , Neoplasias Pulmonares , Adulto , Humanos , Masculino , Hemangioendotelioma Epitelioide/tratamento farmacológico , Hemangioendotelioma Epitelioide/diagnóstico , Imunoterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/diagnóstico , Proteína 2 Homóloga a MutS , Fatores de Transcrição
15.
J Magn Reson Imaging ; 57(1): 216-224, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35749634

RESUMO

BACKGROUND: Perihematomal edema (PHE) is an important determinant of outcome in spontaneous intracerebral hemorrhage (ICH) due to cerebral small vessel disease (CSVD). However, it is not known to date whether the severity of CSVD is associated with the extent of PHE progression in the acute phase. PURPOSE: To investigate the association between the magnetic resonance imaging (MRI) marker of severe chronic-ischemia cerebral small vessel changes (sciSVC) and PHE growth or hematoma absorption among ICH patients with hypertension. STUDY TYPE: Retrospective. POPULATION: Three hundred and sixty-eight consecutive hypertensive ICH patients without surgical treatment. FIELD STRENGTH/SEQUENCE: 3 T; spin-echo echo-planar imaging-diffusion-weighted imaging (DWI); T2-weighted, fluid-attenuated inversion recovery (FLAIR), T2*-weighted gradient-recalled echo and T1-weighted. ASSESSMENT: The hematoma and PHE volumes at 24 hours and 5 days after symptom onset were measured in 121 patients with spontaneous ICH who had been administered standard medical treatment. Patients were grouped into two categories: those with sciSVC and those without. The imaging marker of sciSVC was defined as white matter hyperintensities (WMHs) Fazekas 2-3 combined cavitating lacunes. STATISTICAL TESTS: Univariable analyses, χ2 test, Mann-Whitney U test, and multiple linear regression. RESULTS: The presence of sciSVC (multiple lacunes and confluent WMH) had a significant negative influence on PHE progress (Beta = -5.3 mL, 95% CI = -10.3 mL to -0.3 mL), and hematoma absorption (Beta = -3.2 mL, 95% CI = -5.9 mL to -0.4 mL) compared to that observed in the absence of sciSVC, as determined by multivariate linear regression analysis. DATA CONCLUSIONS: The presence of sciSVC (multiple lacunes and confluent WMH) negatively influenced hematoma absorption and PHE progress in ICH patients. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 3.


Assuntos
Edema Encefálico , Doenças de Pequenos Vasos Cerebrais , Hemorragia Intracraniana Hipertensiva , Humanos , Hemorragia Intracraniana Hipertensiva/complicações , Estudos Retrospectivos , Doenças de Pequenos Vasos Cerebrais/complicações , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Hemorragia Cerebral/complicações , Hemorragia Cerebral/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Hematoma/complicações , Hematoma/diagnóstico por imagem , Edema/complicações
17.
Front Cardiovasc Med ; 9: 966257, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36277788

RESUMO

Objective: This study seeks to evaluate the diagnostic value of computed tomography (CT) in pulmonary hypertension. Method: PubMed, Embase, Scopus, and Web of Science databases were searched to obtain the relevant English literature, and the retrieval time until June 2022. The quality of the included studies is evaluated using the QUADAS-2 tool. The quality of the included studies was assessed, followed by a meta-analysis, analyze heterogeneity, summarize sensitivity and specificity, draw the comprehensive subject working characteristics (sROC) curve, calculate the area under the curve and conduct subgroup analysis and sensitivity analysis to find the source of the heterogeneity. Results: A total of 12 articles were included, all with pulmonary artery diameter/liter aortic diameter >1 or 1 as the diagnostic criteria for pulmonary hypertension, and a total of 1,959 patients were included. Deek's funnel plot analysis suggests that there is no significant publication bias (P = 0.102). The combined sensitivity was 0.652 (95% CI: 0.579, 0.719), combined specificity was 0.830 (95% CI: 0.796, 0.880), positive likelihood ratio was 3.837 (95% CI: 3.215, 4.579), negative likelihood ratio was 0.419 (95% CI: 0.346, 0.507), diagnostic odds ratio was 9.157 (95% CI: 6.748, 12.427) and area under the summary receiver operating characteristic (SROC) curve was 0.84 (95% CI: 0.81, 0.87). Conclusion: The CT examination of pulmonary artery diameter/aortic artery hypertension is worthy of clinical application.

18.
Ann Transl Med ; 10(18): 1013, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36267781

RESUMO

Background: Autism spectrum disorder (ASD) is a specific type of pervasive developmental disorder, and most studies suggest that the onset of autism may be related to genetic and immune factors. The etiology of autism and the underlying molecular events need to be further addressed. Methods: The ASD-related dataset GSE18123 was downloaded from the Gene Expression Omnibus (GEO) database. Gene set enrichment analysis (GSEA) was used to screen for Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways that may be associated with autism. The top 5,000 genes with an absolute median difference were obtained, and a co-expression network was constructed using weighted correlation network analysis (WGCNA). In addition, GO and KEGG enrichment analyses were performed for genes in the modules most closely related to ASD. Hub genes were found in the significant modules, and the expression values and receiver operating characteristic (ROC) curves of the hub genes were analyzed and validated. Immune cell infiltration in ASD was calculated using the CIBERSORT algorithm, and the relationship between hub genes and immune cells was analyzed. Finally, GSEA was used to explore the potential pathways of hub genes affecting ASD. Results: The 5,000 DEGs were divided into eight significant modules by WGCNA. The green module was most significantly associated with ASD, and two hub genes [fatty acid-binding protein 2 (FABP2) and Janus kinase 2 (JAK2)] were found. Immune cell infiltration showed that resting dendritic cells and monocytes differed significantly in ASD and healthy individuals. FABP2 was significantly associated with memory B cells and CD8 T cells. JAK2 was significantly associated with monocytes, CD4 activated memory T cells, CD4 resting memory T cells, activated dendritic cells, gamma delta T cells, regulatory T cells (Tregs), CD8 T cells, and naïve CD4 T cells. FABP2 and JAK2 were found to affect multiple pathways of immunity. Conclusions: FABP2 and JAK2 may influence the immune microenvironment of ASD by regulating immune cells and immune-related pathways and are candidate molecular markers for the development of ASD.

19.
Animals (Basel) ; 12(18)2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36139265

RESUMO

The study was designed with a 2 × 2 factorial experiment to evaluate the effects of growth performance, immune function, antioxidant status, blood biochemical indexes, and hormone levels of donkeys in different housing and management systems in cold weather. Twenty-four male donkeys with similar body weight and age were randomly allocated into four treatment groups that were as follows: a cold-water-drinking group without a windproof facility, a lukewarm-water-drinking group without windproof facilities, a cold-water-drinking group with a windproof facility, and a lukewarm-water-drinking group with a windproof facility. The experiment lasted for 42 days. The results showed that windproof facilities increased average daily gain (ADG) and decreased average daily feed intake (ADFI) and feed-to-gain ratio (F:G) at all time periods (p < 0.01) of the experiment. Windproof facilities increased the digestibility of dry matter (DM), crude fat (CF), crude protein (CP), ash, calcium (Ca), and phosphate (P) on day 21 (p < 0.01), and increased the digestibility of DM, CF, ash, and P on day 42 (p < 0.01). The respiration rate and the skin temperature of the abdomen and legs increased (p < 0.05) and rectal temperature tended to increase (p = 0.083) by adopting windproof facilities at 07:00; the windproof facilities tended to increase the skin temperature of the ears and abdomen (p = 0.081, p = 0.091) at 14:00. For the blood parameters, with windproof facilities, the concentrations of total protein (TP), blood urea nitrogen (BUN), triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) increased (p < 0.05) and glucose (GLU) concentration decreased (p < 0.05) at 07:00 on day 21; the concentrations of TG and cholesterol (CHO) increased and the concentrations of TP, BUN, and GLU decreased at 07:00 on day 42 (p < 0.05). The concentrations of adrenocorticotropic hormone (ACTH), cortisol (COR), triiodothyronine (T3), and thyroxine (T4) decreased (p < 0.05) at 07:00 on day 21, and T4 concentration decreased (p < 0.05) at 07:00 on day 42. The concentrations of interleukin-4 (IL-4), immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) increased (p < 0.01) and the concentrations of interleukin-1ß (IL-1ß) and tumor necrosis factor-alpha (TNF-α) decreased (p < 0.01) on days 21 and 42. The activities of total superoxide dismutase (T-SOD) and glutathione peroxidase (GPx) increased (p < 0.05), and malondialdehyde (MDA) concentration decreased (p < 0.01) on day 21; the activities of T-SOD and catalase (CAT) increased (p < 0.05), and MDA concentration decreased (p < 0.01) on day 42. However, under the conditions of this experiment, water temperature did not affect the above indexes on days 21 and 42. These results indicated that adopting windproof facilities in a cold climate can mitigate the effects of atrocious weather on the production performance of donkeys.

20.
J Thorac Dis ; 14(5): 1401-1410, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35693626

RESUMO

Background: Patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) are eligible for balloon pulmonary angioplasty (BPA). However, the short-term effects of BPA on pulmonary hemodynamics and right ventricular (RV) function in patients with CTEPH have not been elucidated. In the current study, echocardiography was conducted to explore the short-term effects of BPA on inoperable CTEPH patients. Methods: A total of 30 inoperable CTEPH patients who underwent echocardiography before and after BPA were enrolled to the present retrospective study. Right heart catheterization (RHC) parameters, echocardiography function parameters, and echocardiography structural parameters of patients were evaluated at baseline and within 24 hours after BPA and the results were compared. Results: RHC parameters including pulmonary artery systolic pressure (PASP), pulmonary artery diastolic pressure (PADP), mean pulmonary artery pressure (mPAP), and pulmonary vascular resistance (PVR), and echocardiography structural parameters including right atrium diameter (RAD), right ventricular end-diastolic area (RVEDA), right ventricular end-systolic area (RVESA), right atrium end-diastolic area (RAEDA) and right atrium end-systolic area (RAESA) significantly improved within 24 h after BPA compared with the baseline results (P<0.05). However, there were no significant differences in echocardiography function parameters including tissue Doppler-derived tricuspid lateral annular systolic velocity (S'), tricuspid annular plane systolic excursion (TAPSE), right ventricular index of myocardial performance (RIMP), right ventricular fractional area change (RVFAC) and left ventricular stroke volume (LVSV) before and after BPA. Conclusions: The findings show that a single BPA procedure significantly improves RV volume load and reduces the pulmonary blood pressure in CTEPH patients in the short-term. However, BPA does not improve RV systolic function 24 hours after the procedure. The results indicate that evaluation of RV structural and function with echocardiography is an effective approach for non-invasive monitoring of patient status after BPA.

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