Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 221
Filtrar
1.
Cereb Cortex ; 34(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38566508

RESUMO

Physical activity and sedentary behavior, both distinct lifestyle behaviors associated with brain health, have an unclear potential relationship with brain cortical structure. This study aimed to determine the causal link between physical activity, sedentary behavior, and brain cortical structure (cortical surface area and thickness) through Mendelian randomization analysis. The inverse-variance weighted method was primarily utilized, accompanied by sensitivity analyses, to confirm the results' robustness and accuracy. Analysis revealed nominally significant findings, indicating a potential positive influence of physical activity on cortical thickness in the bankssts (ß = 0.002 mm, P = 0.043) and the fusiform (ß = 0.002 mm, P = 0.018), and a potential negative association of sedentary behavior with cortical surface area in the caudal middle frontal (ß = -34.181 mm2, P = 0.038) and the pars opercularis (ß = -33.069 mm2, P = 0.002), alongside a nominally positive correlation with the cortical surface area of the inferior parietal (ß = 58.332 mm2, P = 0.035). Additionally, a nominally significant negative correlation was observed between sedentary behavior and cortical thickness in the paracentral (ß = -0.014 mm, P = 0.042). These findings offer insights into how lifestyle behaviors may influence brain cortical structures, advancing our understanding of their interaction with brain health.


Assuntos
Encéfalo , Análise da Randomização Mendeliana , Encéfalo/diagnóstico por imagem , Exercício Físico , Área de Broca , Estudo de Associação Genômica Ampla
2.
J Colloid Interface Sci ; 667: 520-528, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38653073

RESUMO

Fluorescent probes that specifically targeting Lipid droplets (LDs) have shown potential in biological imaging. Albeit, their in vivo applications are limited due to the hydrophobicity, low signal-to-noise ratio (SNR) and LDs-specificity. Thus, we designed a novel probe namely MeOND, and a reactive oxygen species (ROS)-responsive nano-platform to improve in vivo LDs-specific imaging. MeOND exhibits a remarkable twisted intramolecular charge transfer (TICT) effect with a strongly enhanced near-infrared emission in low-polarity lipid environment. Also, MeOND demonstrates satisfactory biocompatibility and superior intracellular LDs imaging capabilities. MeOND encapsulated nano-platform (MeOND@PMM) presented favorable water solubility and biocompatibility. MeOND@PMM remains stable in physiological conditions but quickly degrades in the environment of elevated ROS level. The released MeOND could then light up the intracellular LDs in atherosclerotic plaques. The design of the probe and nano-platform is expected to provide a better tool for the scientific research of LDs and LDs-related diseases.

3.
Food Res Int ; 182: 114077, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38519167

RESUMO

Fruits flavor deterioration is extremely likely to occur during post-harvest storage, which not only damages quality but also seriously affects its market value. This work focuses on the study of fruits deterioration odorants during storage by describing their chemical compositions (i.e., alcohols, aldehydes, acids, and sulfur-containing compounds). Besides, the specific flavor deterioration mechanisms (i.e., fermentation metabolism, lipid oxidation, and amino acid degradation) inducing by factors (temperature, oxygen, microorganisms, ethylene) are summarized. Moreover, quality control strategies to mitigate fruits flavor deterioration by physical (temperature control, hypobaric treatment, UV-C, CA) and chemical (1-MCP, MT, NO, MeJA) techniques are also proposed. This review will provide useful references for fruits flavor control technologies development.


Assuntos
Frutas , Odorantes , Frutas/química , Aldeídos/análise , Álcoois/análise , Fermentação
4.
Food Chem ; 443: 138578, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38301554

RESUMO

Optimization of seven parameters of stir bar sorptive extraction (SBSE) on mulberry volatile components for the first time. A total of 347 volatile components were identified and quantified in 14 mulberry varieties, predominantly encompassing esters, aldehydes, terpenoids, hydrocarbons, ketones, alcohols, heterocyclics, acids, and phenols. Hexanal and (E)-2-hexenal were the dominant volatiles. Furthermore, 79 volatile compounds characterized by odor activity values (OAVs) > 1 were identified, making a significant contribution to the distinctive mulberry flavor. "Green" notes were the most intense, followed by "fatty" and "fruity". Utilizing odor ring charts, the volatile flavor characteristics of the 14 mulberry varieties could be intuitively distinguished. This study not only established a viable methodology for differentiating mulberry varieties but also laid a theoretical foundation for the quality evaluation and variety breeding of mulberry flavor.


Assuntos
Aldeídos , Morus , Compostos Orgânicos Voláteis , Compostos Orgânicos Voláteis/análise , Melhoramento Vegetal , Cromatografia Gasosa-Espectrometria de Massas/métodos , Frutas/química , Odorantes/análise
5.
J Magn Reson Imaging ; 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38344910

RESUMO

BACKGROUND: Pretreatment identification of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) is important when selecting treatment strategies. PURPOSE: To improve models for predicting MVI and recurrence-free survival (RFS) by developing nomograms containing three-dimensional (3D) MR elastography (MRE). STUDY TYPE: Prospective. POPULATION: 188 patients with HCC, divided into a training cohort (n = 150) and a validation cohort (n = 38). In the training cohort, 106/150 patients completed a 2-year follow-up. FIELD STRENGTH/SEQUENCE: 1.5T 3D multifrequency MRE with a single-shot spin-echo echo planar imaging sequence, and 3.0T multiparametric MRI (mp-MRI), consisting of diffusion-weighted echo planar imaging, T2-weighted fast spin echo, in-phase out-of-phase T1-weighted fast spoiled gradient-recalled dual-echo and dynamic contrast-enhanced gradient echo sequences. ASSESSMENT: Multivariable analysis was used to identify the independent predictors for MVI and RFS. Nomograms were constructed for visualization. Models for predicting MVI and RFS were built using mp-MRI parameters and a combination of mp-MRI and 3D MRE predictors. STATISTICAL TESTS: Student's t-test, Mann-Whitney U test, chi-squared or Fisher's exact tests, multivariable analysis, area under the receiver operating characteristic curve (AUC), DeLong test, Kaplan-Meier analysis and log rank tests. P < 0.05 was considered significant. RESULTS: Tumor c and liver c were independent predictors of MVI and RFS, respectively. Adding tumor c significantly improved the diagnostic performance of mp-MRI (AUC increased from 0.70 to 0.87) for MVI detection. Of the 106 patients in the training cohort who completed the 2-year follow up, 34 experienced recurrence. RFS was shorter for patients with MVI-positive histology than MVI-negative histology (27.1 months vs. >40 months). The MVI predicted by the 3D MRE model yielded similar results (26.9 months vs. >40 months). The MVI and RFS nomograms of the histologic-MVI and model-predicted MVI-positive showed good predictive performance. DATA CONCLUSION: Biomechanical properties of 3D MRE were biomarkers for MVI and RFS. MVI and RFS nomograms were established. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

6.
Heliyon ; 10(4): e25634, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38384574

RESUMO

Primary biliary cholangitis (PBC) is a chronic autoimmune disease of biliary stasis in which immune factors cause the gradual destruction of small bile ducts, biliary stasis, and eventually the development of liver fibrosis, cirrhosis, and even liver failure. One of the main characteristics of PBC is that it primarily affects middle-aged women, but the precise cause is still unknown. This article analyzes the unique causes and mechanisms of the female predominance of PBC and summarizes the potential causes.The female domination of PBC is reported to be primarily caused by sex hormones, environmental circumstances, and epigenetic changes, each of which has a different subtle impact on patients' gender disparities.

7.
Risk Manag Healthc Policy ; 17: 41-48, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38196918

RESUMO

Purpose: We aimed to understand the current situation of smartphone addiction in pregnant women, and explored the moderating effect of self-efficacy between pregnancy stress and smartphone addiction. Patients and Methods: This study adopted a longitudinal design to collect pregnant women from the obstetrics and gynecology department of a tertiary hospital in Shenyang in 2020 from early pregnancy (T1) to their late pregnancy (T2). A total of 342 questionnaires were collected, including the Smartphone Addiction Scale-Short Version (SAS-SV), the Pregnancy Pressure Scale (PPS), and the Chinese version of the General Self-Efficacy Scale (GSES). Multiple hierarchical regression and simple slope test were used to test the moderating effect of self-efficacy. Results: Smartphone addiction in T2 (44.74) was more sever than in T1 (33.11). The interaction item of T1 pregnancy stress and T2 self-efficacy was positively correlated with smartphone addiction (ß=0.205, P<0.01) and explained an additional 3.2% variance (ΔR2=0.032, P<0.01). The influence of pregnancy stress on smartphone addiction was gradually decreased in the low, mean, and high groups of self-efficacy. Conclusion: Smartphone addiction in late pregnancy was more severe than that in early pregnancy, possibly due to increased pregnancy stress. The self-efficacy of pregnant women could reduce the impact of pregnancy stress on smartphone addiction. Medical staff can alleviate the bad behavior by improving their self-efficacy.

8.
Seizure ; 114: 44-49, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38039807

RESUMO

BACKGROUND: Inflammation plays a role in the development and advancement of epilepsy, but the relationship between inflammatory cytokines and epilepsy is still not well understood. Herein, we use two-sample Mendelian randomization (MR) to examine the causal association between systemic inflammatory cytokines and epilepsy. METHODS: We conducted a bidirectional two-sample MR analysis based on genome-wide association study data of 41 serum cytokines from 8293 Finnish individuals with various epilepsy subtypes from the International League against Epilepsy Consortium. RESULTS: Our study showed that three inflammatory cytokines were associated with epilepsy, five were associated with generalized epilepsy, four were associated with focal epilepsy, one was associated with focal epilepsy-documented lesion negative, three were associated with juvenile absence epilepsy, one was associated with childhood absence epilepsy, two were associated with focal epilepsy-documented lesion other than hippocampal sclerosis, and two were associated with juvenile myoclonic epilepsy. Furthermore, the expression of systemic inflammatory cytokines was unaffected by genetically predicted epilepsy. CONCLUSION: This study suggested that several inflammatory cytokines are probably the factors correlated with epilepsy. Additional research is required to ascertain if these biomarkers have therapeutic potential to prevent or manage epilepsy.


Assuntos
Epilepsias Parciais , Epilepsia Tipo Ausência , Humanos , Criança , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Citocinas/genética
9.
Leg Med (Tokyo) ; 67: 102381, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38154315

RESUMO

Uniparental disomy (UPD) is a rare type of chromosomal aberration that may hinder the analysis of kinship during forensic identification. Here, we investigated these genetic findings to avoid false exclusions during parentage testing. Thirty-nine fluorescently labeled, autosomal short tandem repeats (STR) were amplified in three cases, to detect parent-child relationships. Twenty-three fluorescently labeled Y-chromosome STRs were also employed. These were subjected to capillary electrophoresis. The parentage index was calculated by the bipartite or tripartite model. Single nucleotide polymorphism (SNP) microarrays were performed to further investigate the genetic mechanisms. The conclusions supported the biological mother-child relationship in three cases. However, in all cases, the alleged father and child had three autosomal STR markers, constrained to a single chromosome, which did not conform to Mendelian inheritance rules. The genotyping of 23 Y-chromosome STRs did not reveal any violations of Mendelian law. The combination of STR profiling and SNP microarrays suggested that two children had maternal UPD of chromosome 7, whilst one had UPD of chromosome 2. After excluding the three incompatible loci, the conclusions supported the biological father-child relationship in all cases. The same results were obtained when parentage testing of trios was used. Uniparental disomy may complicate the judgment of kinship in parentage testing. The possibility of UPD should be considered when incompatible STR loci are found on the same chromosome. Genetic evidence obtained through additional molecular techniques can provide better interpretation of kinship in the presence of UPD and avoid false exclusions of biological relationships.


Assuntos
Cromossomos Humanos Y , Dissomia Uniparental , Humanos , Dissomia Uniparental/diagnóstico , Dissomia Uniparental/genética , Repetições de Microssatélites/genética , Polimorfismo de Nucleotídeo Único/genética
10.
Front Immunol ; 14: 1301051, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38143759

RESUMO

Atherosclerosis is a common cardiovascular disease caused by the abnormal expression of multiple factors and genes influenced by both environmental and genetic factors. The primary manifestation of atherosclerosis is plaque formation, which occurs when inflammatory cells consume excess lipids, affecting their retention and modification within the arterial intima. This triggers endothelial cell (EC) activation, immune cell infiltration, vascular smooth muscle cell (VSMC) proliferation and migration, foam cell formation, lipid streaks, and fibrous plaque development. These processes can lead to vascular wall sclerosis, lumen stenosis, and thrombosis. Immune cells, ECs, and VSMCs in atherosclerotic plaques undergo significant metabolic changes and inflammatory responses. The interaction of cytokines and chemokines secreted by these cells leads to the onset, progression, and regression of atherosclerosis. The regulation of cell- or cytokine-based immune responses is a novel therapeutic approach for atherosclerosis. Statins are currently the primary pharmacological agents utilised for managing unstable plaques owing to their ability to enhance endothelial function, regulate VSMC proliferation and apoptosis by reducing cholesterol levels, and mitigate the expression and activity of inflammatory cytokines. In this review, we provide an overview of the metabolic changes associated with atherosclerosis, describe the effects of inflammatory responses on atherosclerotic plaques, and discuss the mechanisms through which statins contribute to plaque stabilisation. Additionally, we examine the role of statins in combination with other drugs in the management of atherosclerosis.


Assuntos
Aterosclerose , Inibidores de Hidroximetilglutaril-CoA Redutases , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Aterosclerose/metabolismo , Apoptose , Citocinas
11.
Eur J Radiol ; 168: 111149, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37862927

RESUMO

PURPOSE: Diffusion-weighted imaging (DWI) of the liver suffers from low resolution, noise, and artifacts. This study aimed to investigate the effect of deep learning reconstruction (DLR) on image quality and apparent diffusion coefficient (ADC) quantification of liver DWI at 3 Tesla. METHOD: In this prospective study, images of the liver obtained at DWI with b-values of 0 (DWI0), 50 (DWI50) and 800 s/mm2 (DWI800) from consecutive patients with liver lesions from February 2022 to February 2023 were reconstructed with and without DLR (non-DLR). Image quality was assessed qualitatively using Likert scoring system and quantitatively using signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and liver/parenchyma boundary sharpness from region-of-interest (ROI) analysis. ADC value of lesion were measured. Phantom experiment was also performed to investigate the factors that determine the effect of DLR on ADC value. Qualitative score, SNR, CNR, boundary sharpness, and apparent diffusion coefficients (ADCs) for DWI were compared using paired t-test and Wilcoxon signed rank test. P < 0.05 was considered statistically significant. RESULTS: A total of 85 patients with 170 lesions were included. DLR group showed a higher qualitative score than the non-DLR group. for example, with DWI800 the score was 4.77 ± 0.52 versus 4.30 ± 0.63 (P < 0.001). DLR group also showed higher SNRs, CNRs and boundary sharpness than the non-DLR group. DLR reduced the ADC of malignant tumors (1.105[0.904, 1.340] versus 1.114[0.904, 1.320]) (P < 0.001), but there was no significant difference in the diagnostic value of malignancy for DLR and non-DLR groups (P = 57.3). The phantom study confirmed a reduction of ADC in images with low resolution, and a stronger reduction of ADC in heterogeneous structures than in homogeneous ones (P < 0.001). CONCLUSIONS: DLR improved image quality of liver DWI. DLR reduced the ADC value of lesions, but did not affect the diagnostic performance of ADC in distinguishing malignant tumors on a 3.0-T MRI system.


Assuntos
Aprendizado Profundo , Neoplasias , Humanos , Estudos Prospectivos , Estudos de Viabilidade , Fígado/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos
12.
Mol Psychiatry ; 28(9): 3994-4010, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37833406

RESUMO

The pathogenesis of schizophrenia is believed to involve combined dysfunctions of many proteins including microtubule-associated protein 6 (MAP6) and Kv3.1 voltage-gated K+ (Kv) channel, but their relationship and functions in behavioral regulation are often not known. Here we report that MAP6 stabilizes Kv3.1 channels in parvalbumin-positive (PV+ ) fast-spiking GABAergic interneurons, regulating behavior. MAP6-/- and Kv3.1-/- mice display similar hyperactivity and avoidance reduction. Their proteins colocalize in PV+ interneurons and MAP6 deletion markedly reduces Kv3.1 protein level. We further show that two microtubule-binding modules of MAP6 bind the Kv3.1 tetramerization domain with high affinity, maintaining the channel level in both neuronal soma and axons. MAP6 knockdown by AAV-shRNA in the amygdala or the hippocampus reduces avoidance or causes hyperactivity and recognition memory deficit, respectively, through elevating projection neuron activity. Finally, knocking down Kv3.1 or disrupting the MAP6-Kv3.1 binding in these brain regions causes avoidance reduction and hyperactivity, consistent with the effects of MAP6 knockdown. Thus, disrupting this conserved cytoskeleton-membrane interaction in fast-spiking neurons causes different degrees of functional vulnerability in various neural circuits.


Assuntos
Neurônios , Canais de Potássio de Abertura Dependente da Tensão da Membrana , Camundongos , Animais , Neurônios/metabolismo , Canais de Potássio de Abertura Dependente da Tensão da Membrana/farmacologia , Citoesqueleto/metabolismo , Microtúbulos/metabolismo , Emoções , Canais de Potássio Shaw/metabolismo
13.
Int J Biol Macromol ; 253(Pt 7): 127355, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37838118

RESUMO

Microbial transglutaminase (MTG) is a usable enzyme for biomacromolecule modification. In the present study, a "molecular chaperonin" strategy was developed to produce MTG in E. coli cytoplasm with high expression level and a "small molecule-mediated chemical modification" strategy was adopted to strip propeptide chaperonin efficiently during purification. Propeptide (Pro) was expressed separately as a chaperonin to facilitate MTG expression in E. coli cytoplasm with a yield up to 300 mg or about 9 kU from 1 L fed-batch culture. Furthermore, small molecular chemicals were applied to interfere the interaction between MTG and Pro. Chemical acetylation was identified as a suitable method to strip Pro resulting in pure MTG with high specific activity up to 49.6 U/mg. The purified acetylated MTG was characterized by MS analysis. The deconvoluted mass and Peptide Sequence Tags analysis confirmed acetylation on amino groups of MTG protein. Finally, the applications of obtained MTG were demonstrated via protein polymerization of bovine serum albumin and PEGylation of human interferon-α2b. Our method provides MTG with high purity and specific activity as well as unique merit with masked amino groups thus avoiding self-polymerization and cross-linking between MTG and substrates.


Assuntos
Escherichia coli , Transglutaminases , Humanos , Transglutaminases/genética , Transglutaminases/química , Escherichia coli/metabolismo
14.
J Transl Med ; 21(1): 631, 2023 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-37717019

RESUMO

BACKGROUND: Increasing evidence suggests that hepatocellular carcinoma (HCC) stem cells (LCSCs) play an essential part in HCC recurrence, metastasis, and chemotherapy and radiotherapy resistance. Multiple studies have demonstrated that stemness-related genes facilitate the progression of tumors. However, the mechanism by which stemness-related genes contribute to HCC is not well understood. Here, we aim to construct a stemness-related score (SRscores) model for deeper analysis of stemness-related genes, assisting with the prognosis and individualized treatment of HCC patients.Further, we found that the gene LPCAT1 was highly expressed in tumor tissues by immunohistochemistry, and sphere-forming assay revealed that knockdown of LPCAT1 inhibited the sphere-forming ability of hepatocellular carcinoma cells. METHODS: We used the TCGA-LIHC dataset to screen stemness-related genes of HCC from the MSigDB database. Prognosis, tumor microenvironment, immunological checkpoints, tumor immune dysfunction, rejection, treatment sensitivity, and putative biological pathways were examined. Random forest created the SRscores model. The anti-PD-1/anti-CTLA4 immunotherapy, tumor mutational burden, medication sensitivity, and cancer stem cell index were compared between the high- and low-risk score groups. We also examined risk scores for different cell types using single-cell RNA sequencing data and correlated transcription factor activity in cancer stem cells with SRscores genes. Finally, we tested core marker expression and biological functions. RESULTS: Patients can be divided into two subtypes (Cluster1 and Cluster2) based on the TCGA-LIHC dataset's identification of 11 stemness-related genes. Additionally, a SRscores was developed based on subtypes. Cluster2 and the group with the lowest SRscores had superior survival and immunotherapy response than Cluster1 and the group with the highest SRscores. The group with a high SRscores was significantly more enriched in classical tumor pathways than the group with a low SRscores. Multiple transcription factors and SRscores genes are correlated. The core gene LPCAT1 is highly expressed in rat liver cancer tissues and promotes tumor cell sphere formation. CONCLUSION: A SRscores model can be utilized to predict the prognosis of HCC patients as well as their response to immunotherapy.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Ratos , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Imunoterapia , Bioensaio , Linhagem Celular , Microambiente Tumoral
15.
ACS Omega ; 8(33): 29979-30000, 2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37636928

RESUMO

Thick sequences of terrestrial multicolored mudstones of the Middle Jurassic Shaximiao Formation in the Sichuan Basin, Southwest China, effectively recorded paleoclimate and paleoenvironment changes. The paleoenvironment of the Shaximiao Formation is reconstructed by using detailed sedimentological and elemental geochemical analysis of the multicolored mudstones. The provenance, paleoclimate, paleosalinity, and paleoredox conditions are distinguished by using the discriminant indicators of CIA, C-value, Sr/Cu, Rb/Sr, Th/U, V/Cr, and V/(V + Ni). The results show that all samples derive primarily from felsic igneous rocks and intermediate rocks rather than recycled sediments. The mudstone sequences were deposited under semiarid and semihumid regions with paleoclimate evolved to drier and cooler conditions from lower to upper Shaximiao Formation. Such a paleoclimate coincided with the records of several basins in the lower paleolatitudes of the Northern Hemisphere and were possibly affected by the Middle Jurassic global geological events such as wildfire, paleogeographic reorganizations, and seaway dynamics change. The paleowater body belongs to a typical terrestrial freshwater environment, although the paleosalinity increased significantly during arid periods. The multicolored mudstones were deposited in oxidation and weak-oxidation to weak-anoxic conditions. We also propose a detailed conceptual paleoenvironment model for Shaximiao Formation, with a large perennial lake surrounded by limited alluvial plain during a period of high lake level and small ephemeral lakes scattering extensive alluvial plain during a phase of low lake level.

16.
World J Surg Oncol ; 21(1): 246, 2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37587479

RESUMO

BACKGROUND: NRG1 fusions are rare oncogenic drivers in solid tumors, and the incidence of NRG1 fusions in non-small cell lung cancer (NSCLC) was 0.26%. It is essential to explore potential therapeutic strategies and efficacy predictors for NRG1 fusion-positive cancers. CASE PRESENTATION: We report an advanced lung adenocarcinoma patient harboring a novel NPTN-NRG1 fusion identified by RNA-based next-generation sequencing (NGS), which was not detected by DNA-based NGS at initial diagnosis. Transcriptomics data of the tissue biopsy showed NRG1α isoform accounted for 30% of total NRG1 reads, and NRG1ß isoform was undetectable. The patient received afatinib as fourth-line treatment and received a progression-free survival (PFS) of 14 months. CONCLUSIONS: This report supports afatinib can provide potential benefit for NRG1 fusion patients, and RNA-based NGS is an accurate and cost-effective strategy for fusion detection and isoform identification.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Afatinib/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , RNA , Neuregulina-1/genética
17.
Med Oncol ; 40(9): 274, 2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37608033

RESUMO

TROAP, interacts with trophinin and bystin, polys a key role in embryo implantation. TROAP is required for spindle assembly and centrosome integrity during the mitosis. TROAP has been described to promote tumorigenesis in a diverse range of cancer. We performed this study to assess the biological and clinical significance of TROAP in Non-small cell lung cancer. Forty-eight pairs of lung adenocarcinoma (LUAD) tissues and paraneoplastic tissues were collected. RT-qPCR, western bolt and immunohistochemistry assay was used to test TROAP RNA and protein expression not in LUAD tissues and paraneoplastic tissues but in LUAD cell lines and control cell lines. TROAP knockdown and overexpression vector were constructed and transfected into lung cancer cells. CCK-8, transwell, and wound healing assays were used to assess cell viability, migration, and invasion. The expression of PI3K/AKT and EMT signaling proteins and METTL3 were determined by western blot. We found the TROAP was enriched in NSCLC tissues and cell lines. TROAP knockdown inhibited cell proliferation, migration, invasion compared with control group in NSCLC. Mechanism analysis revealed that TROAP activated PI3K/AKT and EMT signaling pathway. To a certain extent, TROAP was regulated by METTL3. In a word, TROAP accelerated the progression of NSCLC through PI3K/AKT and EMT pathway, and TROAP might be considered as a novel target for NSCLC therapy.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Autoanticorpos , Metiltransferases/genética , Moléculas de Adesão Celular
18.
Artigo em Inglês | MEDLINE | ID: mdl-37581962

RESUMO

It is essential for neuroscience and clinic to estimate the influence of neuro-intervention after brain damage. Most related studies have used Mirrored Contralesional-Ipsilesional hemispheres (MCI) methods flipping the axial neuroimaging on the x-axis in prognosis prediction. But left-right hemispheric asymmetry in the brain has become a consensus. MCI confounds the intrinsic brain asymmetry with the asymmetry caused by unilateral damage, leading to questions about the reliability of the results and difficulties in physiological explanations. We proposed the Separated Left-Right hemiplegia (SLR) method to model left and right hemiplegia separately. Two pipelines have been designed in contradistinction to demonstrate the validity of the SLR method, including MCI and removing intrinsic asymmetry (RIA) pipelines. A patient dataset with 18 left-hemiplegic and 22 right-hemiplegic stroke patients and a healthy dataset with 40 subjects, age- and sex-matched with the patients, were selected in the experiment. Blood-Oxygen Level-Dependent MRI and Diffusion Tensor Imaging were used to build brain networks whose nodes were defined by the Automated Anatomical Labeling atlas. We applied the same statistical and machine learning framework for all pipelines, logistic regression, artificial neural network, and support vector machine for classifying the patients who are significant or non-significant responders to brain-computer interfaces assisted training and optimal subset regression, support vector regression for predicting post-intervention outcomes. The SLR pipeline showed 5-15% improvement in accuracy and at least 0.1 upgrades in [Formula: see text], revealing common and unique recovery mechanisms after left and right strokes and helping clinicians make rehabilitation plans.


Assuntos
Interfaces Cérebro-Computador , Reabilitação Neurológica , Acidente Vascular Cerebral , Humanos , Hemiplegia , Imagem de Tensor de Difusão , Reprodutibilidade dos Testes , Imageamento por Ressonância Magnética
19.
Sci Prog ; 106(3): 368504231189538, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37543182

RESUMO

BACKGROUND: The atresia rate of sphenoid ostium after endoscopic sphenoidotomy for isolated sphenoid disease is 9.4%-10.2%. AIMS: To reduce sphenoid sinus ostium atresia rate after sphenoidotomy surgery. MATERIALS AND METHODS: The data of patients with isolated sphenoid sinus disease at our hospital between 2015 and 2022 were retrospectively analyzed. The age, gender, disease course, pathology, postoperative follow-up time, anatomy data of sphenoid sinus and postoperative sinus ostium atresia rate were compared between the two groups of patients with traditional sphenoidotomy and modified sphenoidotomy. RESULTS: A total of 117 patients with isolated sphenoid sinus disease underwent endoscopic sphenoidotomy. There were 76 cases in the traditional sphenoidotomy group, fungus ball in 59.2% of patients, the postoperative sinus ostium atresia rate was 14.5%. There were 41 cases in the modified sphenoidotomy group, fungus ball in 53.6% of patients, and 0 case of sinus ostium atresia. Statistical analysis showed significant differences in postoperative sinus ostium atresia rate. There was no significant difference in age, pathology, postoperative follow-up time, anatomy data of sphenoid, and other data. CONCLUSIONS AND SIGNIFICANCE: The modified endoscopic sphenoidotomy may reduce the rate of postoperative sinus ostium atresia.


Assuntos
Doenças dos Seios Paranasais , Seio Esfenoidal , Humanos , Seio Esfenoidal/cirurgia , Seio Esfenoidal/microbiologia , Seio Esfenoidal/patologia , Estudos Retrospectivos , Doenças dos Seios Paranasais/patologia , Doenças dos Seios Paranasais/cirurgia , Endoscopia
20.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 40(9): 1068-1074, 2023 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-37643951

RESUMO

OBJECTIVE: To explore the characteristics of copy number variation (CNV) within the Y chromosome azoospermia factor (AZF) region in patients with spermatogenesis disorders in the Shenzhen area. METHODS: A total of 123 patients with spermatogenesis disorders who had visited Shenzhen People's Hospital from January 2016 to October 2022 (including 73 patients with azoospermia and 50 patients with oligozoospermia) and 100 normal semen males were selected as the study subjects. The AZF region was detected with multiplex ligation-dependent probe amplification (MLPA), and the correlation between the CNV in the AZF region and spermatogenesis disorders was analyzed using the chi-square test or Fisher's exact test. RESULTS: 19 CNV were detected among 53 patients from the 223 samples, including 20 cases (27.40%, 20/73) from the azoospermia group, 19 cases (38%, 19/50) from the oligozoospermia group, and 14 cases (14%, 14/100) from the normal control group. In the azoospermia, oligozoospermia, and normal control groups, the detection rates for CNV related to the AZFa region (including AZFab and AZFabc) were 5.48% (4/73), 2.00% (1/50), and 0 (0/100), respectively. The detection rates for the AZFb region (including the AZFbc region) were 6.85% (5/73), 0 (0/50), and 0 (0/100), respectively. The detection rates for gr/gr deletions in the AZFc region were 2.74% (2/73), 6.00% (3/50), and 9.00% (9/100), respectively, and those for b2/b4 deletions in the AZFc region were 2.74% (2/73), 10.00% (5/50), and 0 (0/100), respectively. The detection rates for complex rearrangements in the AZFc region were 6.85% (5/73), 18.00% (9/50), and 3.00% (3/100), respectively. Statistical analysis showed no significant difference in the detection rate of gr/gr deletions between the three groups (Fisher's Exact Test value = 2.712, P = 0.249); the differences in the detection rate of b2/b4 deletions between the three groups were statistically significant (Fisher's Exact Test value = 9.489, P = 0.002); the differences in the detection rate of complex rearrangements in the AZFc region between the three groups were statistically significant (Fisher's Exact Test value = 9.493, P = 0.006). In this study, a rare AZFa region ARSLP1 gene deletion (involving SY86 deletion) was detected in a patient with oligozoospermia. CONCLUSION: CNV in the AZFa and AZFb regions have a severe impact on spermatogenesis, but partial deletion in the AZFa region (ARSLP1 gene deletion) has a minor impact on spermatogenesis. The b2/b4 deletion and complex rearrangement in the AZFc region may be risk factors for male infertility. The gr/gr deletion may not serve as a risk factor for male infertility in the Shenzhen area.


Assuntos
Azoospermia , Infertilidade Masculina , Oligospermia , Humanos , Masculino , Azoospermia/genética , Variações do Número de Cópias de DNA , Oligospermia/genética , Infertilidade Masculina/genética , Cromossomo Y
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...