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1.
Proc Natl Acad Sci U S A ; 121(11): e2317658121, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38437537

ABSTRACT

Identification of mechanisms that program early effector T cells to either terminal effector T (Teff) or memory T (Tm) cells has important implications for protective immunity against infections and cancers. Here, we show that the cytosolic transcription factor aryl hydrocarbon receptor (AhR) is used by early Teff cells to program memory fate. Upon antigen engagement, AhR is rapidly up-regulated via reactive oxygen species signaling in early CD8+ Teff cells, which does not affect the effector response, but is required for memory formation. Mechanistically, activated CD8+ T cells up-regulate HIF-1α to compete with AhR for HIF-1ß, leading to the loss of AhR activity in HIF-1αhigh short-lived effector cells, but sustained in HIF-1αlow memory precursor effector cells (MPECs) with the help of autocrine IL-2. AhR then licenses CD8+ MPECs in a quiescent state for memory formation. These findings partially resolve the long-standing issue of how Teff cells are regulated to differentiate into memory cells.


Subject(s)
CD8-Positive T-Lymphocytes , Cell Division , Cytosol , Reactive Oxygen Species
2.
Anal Chem ; 96(21): 8791-8799, 2024 05 28.
Article in English | MEDLINE | ID: mdl-38742926

ABSTRACT

MicroRNAs (miRNAs) are novel tumor biomarkers owing to their important physiological functions in cell communication and the progression of multiple diseases. Due to the small molecular weight, short sequence length, and low concentration levels of miRNA, miRNA detection presents substantial challenges, requiring the advancement of more refined and sensitive techniques. There is an urgent demand for the development of a rapid, user-friendly, and sensitive miRNA analysis method. Here, we developed an enhanced biotin-streptavidin dual-mode phase imaging surface plasmon resonance (PI-SPR) aptasensor for sensitive and rapid detection of miRNA. Initially, we evaluated the linear sensing range for miRNA detection across two distinct sensing modalities and investigated the physical factors that influence the sensing signal in the aptamer-miRNA interaction within the PI-SPR aptasensor. Then, an enhanced biotin-streptavidin amplification strategy was introduced in the PI-SPR aptasensor, which effectively reduced the nonspecific adsorption by 20% and improved the limit of detection by 548 times. Furthermore, we have produced three types of tumor marker chips, which utilize the rapid sensing mode (less than 2 min) of PI-SPR aptasensor to achieve simultaneous detection of multiple miRNA markers in the serum from clinical cancer patients. This work not only developed a new approach to detect miRNA in different application scenarios but also provided a new reference for the application of the biotin-streptavidin amplification system in the detection of other small biomolecules.


Subject(s)
Aptamers, Nucleotide , Biotin , MicroRNAs , Streptavidin , Surface Plasmon Resonance , MicroRNAs/analysis , MicroRNAs/blood , Biotin/chemistry , Surface Plasmon Resonance/methods , Streptavidin/chemistry , Humans , Aptamers, Nucleotide/chemistry , Limit of Detection , Biomarkers, Tumor/blood , Biomarkers, Tumor/analysis , Biosensing Techniques/methods
3.
Orthod Craniofac Res ; 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38661079

ABSTRACT

OBJECTIVE: This study aims to assess the expansive effects of pterygomaxillary disjunction (PMD) in surgically assisted rapid maxillary expansion (SARME) surgery using a meta-analysis approach. MATERIALS AND METHODS: The study conducted a comprehensive literature search across five databases: PubMed, Scopus, Medline, Embase, and Cochrane, adhering to the PRISMA 2020 guidelines. Dental alterations were assessed using either cone-beam computed tomography (CBCT) or dental casts, while skeletal changes were exclusively measured from CBCT scans. We analysed the dentoskeletal changes between PMD +/- groups and conducted a within-group comparison. The primary focus of the results was on the mean differences observed in pre- and post-operative measurements. RESULTS: Dental expansion was larger in the PMD+ group but not statistically significant. Skeletal expansion showed a significantly larger expansion in the posterior region in the PMD+ group (P = .033). Without PMD, anterior palatal expansion was significantly larger (P = .03), and the buccal tipping of posterior teeth was also significantly larger (P = .011) to achieve acceptable dental expansion outcomes. CONCLUSIONS: Both PMD +/- groups of SARME surgery can achieve satisfactory dental expansion outcomes. However, bone expansion and tooth inclination are also important factors that influence orthodontic treatment and post-expansion stability. By reducing the bony resistance with PMD, larger posterior palatal expansion and more parallel bony expansion are observed. In contrast, without PMD, there is smaller palatal expansion and greater tooth inclination in the posterior region. This could potentially lead to compromised periodontal conditions following expansion.

4.
Nat Commun ; 15(1): 5132, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38879544

ABSTRACT

Electrokinetic force has been the major choice for driving the translocation of molecules through a nanopore. However, the use of this approach is limited by an uncontrollable translocation speed, resulting in non-uniform conductance signals with low conformational sensitivity, which hinders the accurate discrimination of the molecules. Here, we show the use of inertial-kinetic translocation induced by spinning an in-tube micro-pyramidal silicon nanopore fabricated using photovoltaic electrochemical etch-stop technique for biomolecular sensing. By adjusting the kinetic properties of a funnel-shaped centrifugal force field while maintaining a counter-balanced state of electrophoretic and electroosmotic effect in the nanopore, we achieved regulated translocation of proteins and obtained stable signals of long and adjustable dwell times and high conformational sensitivity. Moreover, we demonstrated instantaneous sensing and discrimination of molecular conformations and longitudinal monitoring of molecular reactions and conformation changes by wirelessly measuring characteristic features in current blockade readouts using the in-tube nanopore device.

5.
Article in English | MEDLINE | ID: mdl-38483801

ABSTRACT

Early-stage diabetic retinopathy (DR) presents challenges in clinical diagnosis due to inconspicuous and minute microaneurysms (MAs), resulting in limited research in this area. Additionally, the potential of emerging foundation models, such as the segment anything model (SAM), in medical scenarios remains rarely explored. In this work, we propose a human-in-the-loop, label-free early DR diagnosis framework called GlanceSeg, based on SAM. GlanceSeg enables real-time segmentation of MA lesions as ophthalmologists review fundus images. Our human-in-the-loop framework integrates the ophthalmologist's gaze maps, allowing for rough localization of minute lesions in fundus images. Subsequently, a saliency map is generated based on the located region of interest, which provides prompt points to assist the foundation model in efficiently segmenting MAs. Finally, a domain knowledge filtering (DKF) module refines the segmentation of minute lesions. We conducted experiments on two newly-built public datasets, i.e., IDRiD and Retinal-Lesions, and validated the feasibility and superiority of GlanceSeg through visualized illustrations and quantitative measures. Additionally, we demonstrated that GlanceSeg improves annotation efficiency for clinicians and further enhances segmentation performance through fine-tuning using annotations. The clinician-friendly GlanceSeg is able to segment small lesions in real-time, showing potential for clinical applications.

6.
Front Neurol ; 15: 1361063, 2024.
Article in English | MEDLINE | ID: mdl-38746656

ABSTRACT

Background: Parkinson's disease (PD) is characterized by a range of motor symptoms as well as documented sensory dysfunction. This sensory dysfunction can present itself either as a "pure" sensory disturbance or as a consequence of sensory-motor integration within the central nervous system. This study aims to investigate changes in the functional connectivity of the primary somatosensory cortex (S1) and its clinical significance in Parkinson's disease (PD), an area that has received limited attention in previous neuroimaging studies. Methods: This study included thirty-three patients with PD and thirty-four healthy controls (HCs). Clinical evaluations were conducted to assess the clinical manifestations, severity, and functional capacity of all the patients. Resting-state functional MRI (fMRI) was employed to evaluate the functional connectivity of six paired S1 subregions in the participants. Seed-based correlation (SBC) analysis was utilized to construct the correlation matrix among the subregions and to generate connectivity maps between the subregions and the remaining brain voxels. Finally, the study employed partial least-squares (PLS) correlation analysis to investigate the association between modified functional connectivity and clinical characteristics in PD patients. Results: In the correlation matrix, patients with PD demonstrated a notable decrease in functional connectivity across various S1 subregions in comparison to HCs (p < 0.001, corrected using network-based methods). In connectivity maps, hypo-connectivity was primarily observed in the sensorimotor network as common patterns (p < 0.001, corrected for false discovery rate) and in the default mode network (DMN) as distinct patterns. Moreover, this study identified a negative association between the correlation matrix within S1 subregions and the scores for axial symptoms and postural instability/gait difficulty (PIGD) in PD patients. Nevertheless, a direct relationship between the connectivity maps of S1 subregions and clinical assessment scales was not established. Conclusion: This study offers novel insights into the neurobiological mechanisms that contribute to S1 dysfunction in PD, highlighting the significant involvement of S1 hypo-connectivity in the motor disturbances observed in PD patients.

7.
Comput Biol Med ; 175: 108459, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38701588

ABSTRACT

Diabetic retinopathy (DR) is the most common diabetic complication, which usually leads to retinal damage, vision loss, and even blindness. A computer-aided DR grading system has a significant impact on helping ophthalmologists with rapid screening and diagnosis. Recent advances in fundus photography have precipitated the development of novel retinal imaging cameras and their subsequent implementation in clinical practice. However, most deep learning-based algorithms for DR grading demonstrate limited generalization across domains. This inferior performance stems from variance in imaging protocols and devices inducing domain shifts. We posit that declining model performance between domains arises from learning spurious correlations in the data. Incorporating do-operations from causality analysis into model architectures may mitigate this issue and improve generalizability. Specifically, a novel universal structural causal model (SCM) was proposed to analyze spurious correlations in fundus imaging. Building on this, a causality-inspired diabetic retinopathy grading framework named CauDR was developed to eliminate spurious correlations and achieve more generalizable DR diagnostics. Furthermore, existing datasets were reorganized into 4DR benchmark for DG scenario. Results demonstrate the effectiveness and the state-of-the-art (SOTA) performance of CauDR. Diabetic retinopathy (DR) is the most common diabetic complication, which usually leads to retinal damage, vision loss, and even blindness. A computer-aided DR grading system has a significant impact on helping ophthalmologists with rapid screening and diagnosis. Recent advances in fundus photography have precipitated the development of novel retinal imaging cameras and their subsequent implementation in clinical practice. However, most deep learning-based algorithms for DR grading demonstrate limited generalization across domains. This inferior performance stems from variance in imaging protocols and devices inducing domain shifts. We posit that declining model performance between domains arises from learning spurious correlations in the data. Incorporating do-operations from causality analysis into model architectures may mitigate this issue and improve generalizability. Specifically, a novel universal structural causal model (SCM) was proposed to analyze spurious correlations in fundus imaging. Building on this, a causality-inspired diabetic retinopathy grading framework named CauDR was developed to eliminate spurious correlations and achieve more generalizable DR diagnostics. Furthermore, existing datasets were reorganized into 4DR benchmark for DG scenario. Results demonstrate the effectiveness and the state-of-the-art (SOTA) performance of CauDR.


Subject(s)
Diabetic Retinopathy , Diabetic Retinopathy/diagnostic imaging , Diabetic Retinopathy/diagnosis , Humans , Fundus Oculi , Algorithms , Deep Learning , Image Interpretation, Computer-Assisted/methods
8.
Article in English | MEDLINE | ID: mdl-38900623

ABSTRACT

Conventional approaches to dietary assessment are primarily grounded in self-reporting methods or structured interviews conducted under the supervision of dietitians. These methods, however, are often subjective, potentially inaccurate, and time-intensive. Although artificial intelligence (AI)-based solutions have been devised to automate the dietary assessment process, prior AI methodologies tackle dietary assessment in a fragmented landscape (e.g., merely recognizing food types or estimating portion size), and encounter challenges in their ability to generalize across a diverse range of food categories, dietary behaviors, and cultural contexts. Recently, the emergence of multimodal foundation models, such as GPT-4V, has exhibited transformative potential across a wide range of tasks (e.g., scene understanding and image captioning) in various research domains. These models have demonstrated remarkable generalist intelligence and accuracy, owing to their large-scale pre-training on broad datasets and substantially scaled model size. In this study, we explore the application of GPT-4V powering multimodal ChatGPT for dietary assessment, along with prompt engineering and passive monitoring techniques. We evaluated the proposed pipeline using a self-collected, semi free-living dietary intake dataset comprising 16 real-life eating episodes, captured through wearable cameras. Our findings reveal that GPT-4V excels in food detection under challenging conditions without any fine-tuning or adaptation using food-specific datasets. By guiding the model with specific language prompts (e.g., African cuisine), it shifts from recognizing common staples like rice and bread to accurately identifying regional dishes like banku and ugali. Another GPT-4V's standout feature is its contextual awareness. GPT-4V can leverage surrounding objects as scale references to deduce the portion sizes of food items, further facilitating the process of dietary assessment.

9.
Light Sci Appl ; 13(1): 2, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38161210

ABSTRACT

Rapid plasmonic biosensing has attracted wide attention in early disease diagnosis and molecular biology research. However, it was still challenging for conventional angle-interrogating plasmonic sensors to obtain higher sensitivity without secondary amplifying labels such as plasmonic nanoparticles. To address this issue, we developed a plasmonic biosensor based on the enhanced lateral position shift by phase singularity. Such singularity presents as a sudden phase retardation at the dark point of reflection from resonating plasmonic substrate, leading to a giant position shift on reflected beam. Herein, for the first time, the atomically thin layer of Ge2Sb2Te5 (GST) on silver nanofilm was demonstrated as a novel phase-response-enhancing plasmonic material. The GST layer was not only precisely engineered to singularize phase change but also served as a protective layer for active silver nanofilm. This new configuration has achieved a record-breaking largest position shift of 439.3 µm measured in calibration experiments with an ultra-high sensitivity of 1.72 × 108 nm RIU-1 (refractive index unit). The detection limit was determined to be 6.97 × 10-7 RIU with a 0.12 µm position resolution. Besides, a large figure of merit (FOM) of 4.54 × 1011 µm (RIU∙°)-1 was evaluated for such position shift interrogation, enabling the labelfree detection of trace amounts of biomolecules. In targeted biosensing experiments, the optimized sensor has successfully detected small cytokine biomarkers (TNF-α and IL-6) with the lowest concentration of 1 × 10-16 M. These two molecules are the key proinflammatory cancer markers in clinical diagnosis, which cannot be directly screened by current clinical techniques. To further validate the selectivity of our sensing systems, we also measured the affinity of integrin binding to arginylglycylaspartic acid (RGD) peptide (a key protein interaction in cell adhesion) with different Mn2+ ion concentrations, ranging from 1 nM to 1 mM.

11.
Article in Zh | WPRIM | ID: wpr-1035960

ABSTRACT

Objective:To evaluate the clinical efficacy, tolerability and safety of adjunctive perampanel in focal epilepsy patients≥12 years old.Methods:One hundred and nineteen focal epilepsy patients≥12 years old accepted adjunctive perampanel in Department of Neurology, First Affiliated Hospital of Guangxi Medical University from July 2020 to December 2022 were chosen. At 1-3 months, 4-6 months, 7-9 months and 10-12 months after adjunctive perampanel, seizure frequency changes every 28 d, medication retention rate and adverse reactions were recorded to evaluate the clinical efficacy (a reduction in seizure frequency≥50% from baseline was defined as overall valid treatment), tolerability and safety of adjunctive perampanel. According to efficacy results after adjunctive perampanel of 4-6 months (short-term) and 10-12 months (long-term), these patients were divided into valid group and invalid group; and the influencing factors for short-term and long-term efficacy were analyzed.Results:At 1-3, 4-6, 7-9, 10-12 months after adjunctive perampanel, reduction in seizure frequency every 28 d was 66.7% (24.3%, 97.2%), 77.5% (48.6%, 100%), 94.6% (50%, 100%), 100% (70.9%, 100%), enjoying overall valid rate of 60.2% (59/98), 75.0% (7/76), 78.9% (45/57), 86.5% (32/37). The retention rate at 3, 6, 9 and 12 months after adjunctive perampanel was 85.2% (98/115), 67.9% (76/112), 54.3% (57/105), 41.1% (37/90). Adverse reactions were reported in 33 patents (27.7%), mainly with dizziness and secondly with mental symptoms. After short-term and long-term adjunctive perampanel, no significant difference was noted in gender, initial age of adjunctive perampanel, course of disease, etiology, EEG results, imaging results, number and type of combined anti-seizure drugs, or maximum dose of pirampanel between the valid group and invalid group ( P>0.05). Conclusion:Perampanel has good efficacy, tolerability and safety in adolescents and adults≥12 years old with focal epilepsy; no clear influencing factors for pirampanel valid treatment is found so far.

12.
Article in Zh | WPRIM | ID: wpr-990077

ABSTRACT

The incidences of both autism spectrum disorder and food allergy have been on the rise in the past few decades, which have become global public health problems.Autism spectrum disorder is a complex neurodevelopmental disorder commonly associated with gastrointestinal problems.The exact etiology and pathogenesis are unclear, and immune dysfunction has been shown associated with autism spectrum disorder.Food allergy is an immune-mediated disease that often causes gastrointestinal symptoms.Some studies have reported a possible link between food allergy and autism spectrum disorder.This reviews describes the correlation between food allergy and autism spectrum disorder, aiming to provide information for the study of etiology and treatment of autism spectrum disorder.

13.
Acta Physiologica Sinica ; (6): 115-129, 2023.
Article in Zh | WPRIM | ID: wpr-970112

ABSTRACT

Acute kidney injury (AKI) is a common critical disease clinically with high morbility and mortality and some survival patients also progress to chronic kidney disease. Renal ischemia-reperfusion (IR) is one of the main causes of AKI, in which, its repair and potential fibrosis, apoptosis, inflammation and phagocytosis play important roles. During the progression of IR-induced AKI, the expression of erythropoietin homodimer receptor (EPOR)2 and EPOR and β common receptor formed heterodimer receptor (EPOR/βcR) is changed dynamically. Moreover, (EPOR)2 and EPOR/βcR may synergistically participate in renoprotection at the stage of AKI and early repair, whereas at the late stage of AKI, the (EPOR)2 induces renal fibrosis and the EPOR/βcR facilitates repair and remodelling. The underlying mechanism, signaling pathways and the different effect turning point of (EPOR)2 and EPOR/βcR have not been well defined. It has been reported that EPO, according to its 3D structure, derived helix B surface peptide (HBSP) and cyclic HBSP (CHBP) only bind to EPOR/βcR. Synthesized HBSP, therefore, provides an effective tool to distinguish the different roles and mechanisms of both receptors, with the (EPOR)2 promoting fibrosis or the EPOR/βcR leading to repair/remodelling at the late stage of AKI. This review discusses the similarities and differences of (EPOR)2 and EPOR/βcR in their impacts on apoptosis, inflammation and phagocytosis in AKI, repair and fibrosis post IR, associated mechanisms, signaling pathways and outcomes.


Subject(s)
Humans , Receptors, Erythropoietin , Acute Kidney Injury , Apoptosis , Inflammation , Phagocytosis , Reperfusion Injury
14.
Chinese Medical Ethics ; (6): 679-683, 2023.
Article in Zh | WPRIM | ID: wpr-1005689

ABSTRACT

【Objective:】 To explore the correlation between hospital ethics atmosphere and work engagement of nurses in emergency department, and provide a basis for reasonably solving ethical issues and improving nurses’ work engagement. 【Methods:】 From May 2019 to May 2021, the convenient sampling method was used to select 350 nurses from emergency departments of four tertiary or above hospitals in Xi’an as the research subjects. The Ethical Climate Cognitive Scale and the Work Engagement Scale were used to evaluate the hospital ethical atmosphere and work engagement of nurse, and analyze their correlation. The univariate factor analysis and multiple factor analysis were used to explore the influencing factors. 【Results:】 The work engagement score of emergency department nurses was (51.69±11.09) points, and the ethical atmosphere score was (72.78±11.45) points. The results of univariate analysis showed that there were statistically significant differences in the work engagement scores among emergency department nurses with different educational backgrounds, hospital grades, hospital employment methods, and whether they had received ethics training (P<0.05). The results of multiple factor analysis indicated that the cognition of hospital ethical atmosphere, hospital employment methods, and whether they had received ethics education and training were all factors that affected work engagement (P<0.05). 【Conclusion:】 The hospital ethical atmosphere is positively correlated with the work engagement of emergency department nurse. The ethical atmosphere and work engagement of nurses are both at a moderate level, with significant room for improvement. Therefore, it is necessary to continue to strengthen the management support of emergency nursing work and improve the perceived level of recognition and respect among emergency department nurses in the organization.

15.
Article in Zh | WPRIM | ID: wpr-970451

ABSTRACT

Objective To explore the preliminary application of single-cell RNA sequencing (scRNA-seq) in the renal arterial lesions in Takayasu arteritis (TA) patients. Methods This study included 2 TA patients with renal artery stenosis treated by bypass surgery in the Department of Vascular Surgery,Beijing Hospital.The obtained 2 renal artery samples were digested with two different protocols (GEXSCOPE kit and self-made digestion liquid) before scRNA-seq and bioinformatics analysis. Results A total of 2920 cells were obtained for further analysis.After unbiased cluster analysis,2 endothelial cell subsets,2 smooth muscle cell subsets,1 fibroblast subset,2 mononuclear macrophage subsets,1 T cell subset,and 1 undefined cell subset were identified.Among them,the two subsets of smooth muscle cells were contractile and secretory,respectively.The results of scRNA-seq indicated that enzymatic hydrolysis with GEXSCOPE kit produced a large number of endothelial cells (57.46%) and a small number of immune cells (13.21%).However,immune cells (34.64%) were dominant in the cells obtained by enzymatic hydrolysis with self-made digestive liquid. Conclusion scRNA-seq can be employed to explore the cellular heterogeneity of diseased vessels in TA patients.Different enzymatic digestion protocols may impact the proportion of different cells.


Subject(s)
Humans , Takayasu Arteritis , Endothelial Cells , Transcriptome , Computational Biology , Fibroblasts
16.
China Occupational Medicine ; (6): 489-496, 2023.
Article in Zh | WPRIM | ID: wpr-1013314

ABSTRACT

{L-End}Objective To study the intervention effect of hydrogen on early inflammation in a rat silicosis model and its mechanism. {L-End}Methods Wistar rats of specific pathogen free were randomly divided into the control group, model group, tetrandrine group, hydrogen group and combined intervention group, with 10 rats in each group. The rats in the last four groups were treated with a dose of l.00 mL silica suspension with a mass concentration of 50.0 g/L by a one-time non-exposed tracheal method. The rats in the control group were given 0.9% sodium chloride solution in equal volume. After 24 hours of dust exposure, rats of the tetrandrine group were given 30 mg/kg body mass tetrandrine by gavage daily, rats of the hydrogen group were given 66.6% hydrogen inhalation continuously for four hours daily, rats of the combined intervention group were given the same interventions as the rats in the tetrandrine group and the hydrogen group, rats in the control group and model group were given 0.9% sodium chloride solution in equal volume by gavage. After 14 days of treatment, the lung coefficient of rats was determined, and lung histopathology was performed. The level of malondialdehyde in serum was detected by colorimetry. The level of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in serum were detected by enzyme-linked immunosorbent assay. The relative expression of nucleotide-binding oligomerization domain-like receptor thermal protein domain associated protein 3 (NLRP3), nuclear factor-κB (NF-κB) p65, NF-κB phosphorylated p65 (NF-κB p-p65), cysteinyl aspartate specific proteinase1 (Caspase1) and apoptosis-associated speck-like protein containing a CARD (ASC) in serum were detected in lung tissues by Western blot. The relative expression of NLRP3 and NF-κB p65 in lung tissues were detected by immunohistochemistry. {L-End}Results The result of pulmonary histopathology showed that the model group had obvious alveolar rupture and fusion, interstitial lymphocyte and macrophage infiltration, and alveolar wall thickening, collagen fibre deposition, and mild fibrotic hyperplasia, compared with the control group. The pathological outcomes of lung tissues in the three treated groups were alleviated compared with the model group, and the alveolar structure was more complete and the alveolar wall was thinner and the fewer collagen fibres in the rats of combined intervention group, compared with tetrandrine group and hydrogen group. The lung coefficient and Szapiel score of rats of the tetrandrine group, hydrogen group and combined intervention group were lower than those of the model group (all P<0.05). The levels of serum malondialdehyde, TNF-α and IL-1β in lung tissues, and the relative expression of NLRP3, NF-κB p65, NF-κB P-p65, Caspase1 and ASC in lung tissues increased in the model group, compared with the control group (all P<0.05). The indexes above decreased in the three treated groups than those in the model group (all P<0.05). The indexes above decreased in the combined intervention group than those in the tetrandrine group and hydrogen group (all P<0.05), except for the level of malondialdehyde in serum and the relative expression of NF-κB p-p65 in lung tissue. {L-End}Conclusion Hydrogen can intervene the early inflammation of silicosis through NF-κB/ NLRP3 signaling pathway.

17.
Article in Zh | WPRIM | ID: wpr-1015659

ABSTRACT

Intermittent hypoxia (IH) is an important pathophysiological feature of obstructive sleep apnea (OSA), but its molecular mechanism is still unclear. We aim to investigate the role of endogenous competing endogenous RNA (ceRNA) regulatory network in the development of IH in OSA rats. An intermittent hypoxic rat model of OSA was constructed by hypoxic and reoxygenation cycles. CircRNAs and mRNAs were detected in rat bronchial tissues, and 230 up-regulated and 181 down-regulated circRNAs and 1238 up-regulated and 608 down-regulated mRNAs were analyzed and screened. The results of Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the differential circRNAs and mRNAs suggested that they were mainly associated with metabolic pathways and PI3K-Akt signaling pathways. The key circRNAs (the top six circRNAs with the largest differences) were further validated by quantitative real-time polymerase chain reaction (qRT-PCR), chr9:52042693| 52047844 and chr4: 64889575|64899587 were expressed in bronchial tissues consistent with the sequencing results, which were used to further construct the ceRNA regulatory network. Four potential ceRNA regulatory networks were identified by TargetScan and miRanda database, combined with the results of differential circRNA and mRNA. The expression of molecules in the four potential ceRNA regulatory networks was detected by qRT-PCR in bronchial and lung tissues, and the results suggested that the expression of this regulatory network, chr9:52042693|52047844-miR-351-5p-Pten, was consistent with the sequencing results. The findings indicate that chr9:52042693 | 52047844-miR-351-5p-Pten may be involved in the development and progression of obstructive sleep apnea syndrome through a ceRNA mechanism.

18.
China Pharmacy ; (12): 1326-1331, 2023.
Article in Zh | WPRIM | ID: wpr-974679

ABSTRACT

OBJECTIVE To study the effects of Yishen daluo decoction on inflammatory factors and cyclic adenosine monophosphate(cAMP)/protein kinase A (PKA)/cAMP response element binding protein (CREB) signal pathway in experimental autoimmune encephalomyelitis (EAE) model mice by inhibiting the expressions of β-arrestin1, and to explore the mechanism of Yishen daluo decoction in the treatment of EAE. METHODS Sixty mice were randomly divided into normal group, model group, TCM group (Yishen daluo decoction 20 g/kg), positive control group (prednisone acetate 3.9 mg/kg), β-arrestin1 siRNA adeno- associated virus (AAV-β) group, AAV-β+TCM group, with 10 mice in each group. Except for normal group, EAE model was made in other groups. AAV-β group and AAV-β+TCM group were injected with AAV-β via tail vein to interfere with the expression of β -arrestin1 protein. Starting from the 8th day of modeling, they were given corresponding drug solution/normal saline intragastrically, once a day, for consecutive 14 days. The neurological function score of mice was detected; the pathological and morphological changes were observed in the brain and spinal cord tissues of mice; the serum levels of inflammatory factors [interleukin-2 (IL-2), IL-23, interferon-γ (IFN-γ)] in mice were determined; the expressions of β-arrestin1, cAMP, PKA and CREB in brain and spinal cord were detected. RESULTS Compared with normal group, neurological function scores, serum levels of inflammatory factors, and protein expressions of β-arrestin1 in brain and spinal cord were significantly increased (P<0.05 or P< 0.01); protein expressions of PKA, CREB and cAMP in brain and spinal cord were decreased significantly(P<0.05 or P<0.01). The deep staining of cellular shrinkage and aggregation of inflammatory cells were observed in most neurons of the brain and spinal cord, with varying degrees of demyelinating. Compared with model group, the neurological function scores, pathological changes in brain and spinal cord tissues, and most indicators (except for CREB and cAMP proteins in the brain tissue of AAV-β group) were significantly reversed (P<0.05 or P<0.01).Compared with AAV- β group, the neurological function scores, the levels of IFN-γ in serum and β-arrestin1 in spinal cord were significantly decreased (P<0.05 or P<0.01), PKA and cAMP in brain and spinal cord tissues were significantly increased in AAV- β +TCM group (P<0.05 or P<0.01). CONCLUSIONS Yishen daluo decoction can inhibit the expression of β-arrestin1 in the central nervous system thus activating the cAMP/PKA/CREB signaling pathway, relieving nervous system inflammation, and ultimately alleviates the symptoms of EAE.

19.
Article in Zh | WPRIM | ID: wpr-986046

ABSTRACT

Objective: To investigate and understand the medical security and quality of life of migrant workers with pneumoconiosis, so as to provide scientific basis for the prevention and control countermeasures of migrant workers with pneumoconiosis and targeted poverty alleviation. Methods: Using a stratified random sampling method, 200 migrant workers diagnosed with pneumoconiosis at the Shandong Academy of Occupational Health and Occupational Medicine from January 2016 to December 2021 were selected as the observation group, while 200 non migrant workers diagnosed with pneumoconiosis were selected as the control group. St. George's Respiratory Questionnaire (SGRQ) and Pneumoconiosis Questionnaire were used to collect and compare information on the age, working age of dust exposure, economic sources, employment status, income, medical security and quality of life of two groups of patients. Results: The age of migrant worker pneumoconiosis patients in the observation group was (58.1±8.1) years old, and the working age of dust exposure was (19.3±10.1) years. The main source of income was children support (85.5%, 171/200), employment status was mainly wait for employment or unemployed (69.0%, 138/200), personal monthly income was mainly non income (90.0%, 180/200), and family annual income was mainly less than 10000 yuan (48.0%, 96/200). The average personal annual medical expenditure of 5000-<10000 yuan accounted for 42.0% (84/200). The age of pneumoconiosis patients in the control group was (59.2±8.9) years old, and the working age of dust exposure was (20.2±10.5) years. The main source of income was retirement pension or salary (99.0%, 198/200), with retirement as the main employment status (66.0%, 132/200), the main personal monthly income was 2000-<4000 yuan (61.5%, 123/200), the main family annual income was 20000-<40000 yuan (44.0%, 88/200), and the average personal annual medical expenditure was mostly non-expenditure (92.0%, 184/200). There were statistically significant differences in the distribution of economic sources, employment status, personal monthly income, family annual income and average personal annual medical expenditure between the two groups (P<0.001). The main type of insurance for the observation group was rural cooperative medical care (68.5%, 137/200), and 87.0% (174/200) had no medical reimbursement and a proportion less than 50%. There were statistically significant differences in insurance type and medical reimbursement proportion between the two groups (P<0.001). The respiratory symptoms, activity ability, daily life influence and total quality of life scores of pneumoconiosis patients in the observation group were significantly higher than those in the control group, the differences were statistically significant (P<0.001) . Conclusion: Migrant workers with pneumoconiosis have low income, high medical expenditure, low medical reimbursement proportion and poor quality of life. Therefore, it is necessary to draw high attention from relevant departments and provide timely attention and assistance to improve the quality of life of migrant workers with pneumoconiosis.


Subject(s)
Child , Humans , Middle Aged , Aged , Adolescent , Young Adult , Adult , Quality of Life , Pneumoconiosis , Income , Employment , Dust , China
20.
Journal of Experimental Hematology ; (6): 1327-1332, 2023.
Article in Zh | WPRIM | ID: wpr-1009989

ABSTRACT

OBJECTIVE@#To analyze the immunological phenotype of chronic myeloid leukemia (CML), and explore its characteristics and significance.@*METHODS@#The immunophenotypes of 40 CML children and 40 controls were analyzed by multicolor flow cytometry. CD45/SSC, as the basic gate, was used to delineate neutrophils. Then, the distribution of cluster differentiation (CD) molecules on the surface of granulocytes was analyzed in three ranges (≥1%, ≥5%, and ≥20%), and the expression rates of CD molecules (≥1% included in the statistical analysis) and the mean fluorescence intensity (MFI) were compared between the two groups.@*RESULTS@#The proportion of granulocytes in the CML group was (82.1±6.4)%, which was significantly higher than (57.8±11.8)% in the control group (P <0.001). The expression rates of CD15/CD11b/CD33/CD13 in CML and control groups were high, and both distributed in the range of ≥20%. The differentiation trajectory of CD33/CD13 was normal and there were no significant differences in the expression rate and MFI between the two groups. However, both the expression rate of CD11b and CD15 MFI in the CML group were significantly lower than those in the control group (P <0.001). There were no significant differences in the expression rate and MFI of CD10 between the two groups, and the expression levels of CD10 between the two groups were consistent in different distributions. In the CML group, there was a large number of cases with abnormal high expression of CD56, 52.5% of the cases had a CD56 expression rate of ≥5%, and 42.5% had a CD56 expression rate of ≥20%, while the control group did not express CD56 (<1%). The expression distribution of CD117 was different between the two groups. In the range of expression rate ≥5%, there were 35.0% cases in the CML group, while only 2.5% in the control group. The expression rate of CD117 in the CML group was higher than that in the control group (P <0.001), though there was no significant difference in MFI.@*CONCLUSION@#The immunophenotyping of CML is characterized by increased proportion of mature neutrophils, decreased CD15 MFI, decreased proportion of CD11b and abnormal high expression of CD56 and CD117. Flow cytometric analysis of immunophenotype can effectively distinguish normal granulocytes from chronic granulocytes, and help in the diagnosis of CML.


Subject(s)
Child , Humans , Flow Cytometry , Leukemia, Myeloid , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Granulocytes , Neutrophils , Immunophenotyping
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