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1.
Biomark Med ; : 1-6, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39136398

ABSTRACT

Aim: We hypothesized plasma sEH activity correlates with mortality in acute respiratory distress syndrome (ARDS) patients. Methods: Adult patients diagnosed with ARDS enrolled between 2017 and 2019 were included in this study. Results: A total of 337 adult patients met our inclusion criteria. Among them, 107 patients died within 28 days. The plasma sEH activity was higher in nonsurvivors relative to survivors. And a receiver operating characteristic curve with the area under the curve of 0.81 (95% confidence interval: 0.74-0.89) for the prediction of 28-day mortality was obtained. Its sensitivity and specificity were 72.5% and 74.6%, respectively. Conclusion: Elevated plasma sEH activity is associated with higher 28-day mortality in adult patients with ARDS.


[Box: see text].

2.
J Pain Res ; 17: 2165-2190, 2024.
Article in English | MEDLINE | ID: mdl-38910593

ABSTRACT

Background: The increasing utilization of endoscopic lumbar discectomy (ELD) in spinal surgery has sparked widespread interest and research. This study utilizes bibliometric analysis to identify current research trends and advancements in this innovative surgical technique, with the goal of informing and improving surgical practices. Methods: We retrieved relevant literature on ELD from the Science Citation Index Expanded (SCI-Expanded) within the Web of Science Core Collection (WoSCC) database as research samples. Various visualization tools, such as VOSviewer, CiteSpace, Scimago Graphica, Pajek, and online bibliometric platform, were employed to generate scientific knowledge maps for the purpose of visual presentation and data analysis. Results: Over the past two decades, there has been significant progress in the research related to ELD, particularly since 2016. China has emerged as the most productive country, while South Korea and the United States have exerted greater academic influence. Tongji University has contributed the highest number of research output, while academic achievements published by Wooridul Spine Hospital are highly esteemed by scholars. Lee SH and Ruetten S are the most prolific author and the most highly cited author, respectively. World Neurosurg has published the highest number of publications, while Spine has become the most influential journal. Clinical Neurology and Surgery are the primary subject categories. Research in this field primarily revolves around improving ELD techniques, evaluating postoperative efficacy and prognosis prediction, studying complications and risk factors, as well as comparative research with other surgical techniques. Keywords such as risk factors, LDH, PETD, lumbar spinal stenosis, degeneration, recurrent herniation, laminectomy, local anesthesia, and foraminoplasty highlight the current research hotspots and future cutting-edge trends. Conclusion: This study employed bibliometric analysis to elucidate the research hotspots and frontiers in ELD. The findings have significant implications for advancing research and development in this field.

3.
Cell Commun Signal ; 22(1): 308, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38831451

ABSTRACT

Gasdermin D (GSDMD) is emerging as an important player in autoimmune diseases, but its exact role in lupus nephritis (LN) remains controversial. Here, we identified markedly elevated GSDMD in human and mouse LN kidneys, predominantly in CD11b+ myeloid cells. Global or myeloid-conditional deletion of GSDMD was shown to exacerbate systemic autoimmunity and renal injury in lupus mice with both chronic graft-versus-host (cGVH) disease and nephrotoxic serum (NTS) nephritis. Interestingly, RNA sequencing and flow cytometry revealed that myeloid GSDMD deficiency enhanced granulopoiesis at the hematopoietic sites in LN mice, exhibiting remarkable enrichment of neutrophil-related genes, significant increases in total and immature neutrophils as well as granulocyte/macrophage progenitors (GMPs). GSDMD-deficient GMPs and all-trans-retinoic acid (ATRA)-stimulated human promyelocytes NB4 were further demonstrated to possess enhanced clonogenic and differentiation abilities compared with controls. Mechanistically, GSDMD knockdown promoted self-renewal and granulocyte differentiation by restricting calcium influx, contributing to granulopoiesis. Functionally, GSDMD deficiency led to increased pathogenic neutrophil extracellular traps (NETs) in lupus peripheral blood and bone marrow-derived neutrophils. Taken together, our data establish that GSDMD deletion accelerates LN development by promoting granulopoiesis in a calcium influx-regulated manner, unraveling its unrecognized critical role in LN pathogenesis.


Subject(s)
Calcium , Lupus Nephritis , Phosphate-Binding Proteins , Lupus Nephritis/pathology , Lupus Nephritis/metabolism , Lupus Nephritis/genetics , Animals , Humans , Mice , Phosphate-Binding Proteins/metabolism , Phosphate-Binding Proteins/genetics , Phosphate-Binding Proteins/deficiency , Calcium/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/deficiency , Neutrophils/metabolism , Granulocytes/metabolism , Myeloid Cells/metabolism , Mice, Inbred C57BL , Female , Extracellular Traps/metabolism , Cell Differentiation , Gasdermins
4.
Cell Death Dis ; 15(6): 397, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38844455

ABSTRACT

Integrin αvß6 holds promise as a therapeutic target for organ fibrosis, yet targeted therapies are hampered by concerns over inflammatory-related side effects. The role of αvß6 in renal inflammation remains unknown, and clarifying this issue is crucial for αvß6-targeted treatment of chronic kidney disease (CKD). Here, we revealed a remarkable positive correlation between overexpressed αvß6 in proximal tubule cells (PTCs) and renal inflammation in CKD patients and mouse models. Notably, knockout of αvß6 not only significantly alleviated renal fibrosis but also reduced inflammatory responses in mice, especially the infiltration of pro-inflammatory macrophages. Furthermore, conditional knockout of αvß6 in PTCs in vivo and co-culture of PTCs with macrophages in vitro showed that depleting αvß6 in PTCs suppressed the migration and pro-inflammatory differentiation of macrophages. Screening of macrophage activators showed that αvß6 in PTCs activates macrophages via secreting IL-34. IL-34 produced by PTCs was significantly diminished by αvß6 silencing, and reintroduction of IL-34 restored macrophage activities, while anti-IL-34 antibody restrained macrophage activities enhanced by αvß6 overexpression. Moreover, RNA-sequencing of PTCs and verification experiments demonstrated that silencing αvß6 in PTCs blocked hypoxia-stimulated IL-34 upregulation and secretion by inhibiting YAP expression, dephosphorylation, and nuclear translocation, which resulted in the activation of Hippo signaling. While application of a YAP agonist effectively recurred IL-34 production by PTCs, enhancing the subsequent macrophage migration and activation. Besides, reduced IL-34 expression and YAP activation were also observed in global or PTCs-specific αvß6-deficient injured kidneys. Collectively, our research elucidates the pro-inflammatory function and YAP/IL-34/macrophage axis-mediated mechanism of αvß6 in renal inflammation, providing a solid rationale for the use of αvß6 inhibition to treat kidney inflammation and fibrosis.


Subject(s)
Integrins , Macrophages , Mice, Knockout , Renal Insufficiency, Chronic , Animals , Macrophages/metabolism , Mice , Humans , Integrins/metabolism , Renal Insufficiency, Chronic/pathology , Renal Insufficiency, Chronic/metabolism , Inflammation/pathology , Inflammation/metabolism , Male , Antigens, Neoplasm/metabolism , Mice, Inbred C57BL , Signal Transduction , Disease Models, Animal , YAP-Signaling Proteins/metabolism , Kidney Tubules, Proximal/metabolism , Kidney Tubules, Proximal/pathology , Fibrosis
5.
Immunity ; 57(6): 1306-1323.e8, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38815582

ABSTRACT

Group 3 innate lymphoid cells (ILC3s) regulate inflammation and tissue repair at mucosal sites, but whether these functions pertain to other tissues-like the kidneys-remains unclear. Here, we observed that renal fibrosis in humans was associated with increased ILC3s in the kidneys and blood. In mice, we showed that CXCR6+ ILC3s rapidly migrated from the intestinal mucosa and accumulated in the kidney via CXCL16 released from the injured tubules. Within the fibrotic kidney, ILC3s increased the expression of programmed cell death-1 (PD-1) and subsequent IL-17A production to directly activate myofibroblasts and fibrotic niche formation. ILC3 expression of PD-1 inhibited IL-23R endocytosis and consequently amplified the JAK2/STAT3/RORγt/IL-17A pathway that was essential for the pro-fibrogenic effect of ILC3s. Thus, we reveal a hitherto unrecognized migration pathway of ILC3s from the intestine to the kidney and the PD-1-dependent function of ILC3s in promoting renal fibrosis.


Subject(s)
Cell Movement , Fibrosis , Kidney , Lymphocytes , Programmed Cell Death 1 Receptor , Receptors, CXCR6 , Receptors, Interleukin , Signal Transduction , Animals , Fibrosis/immunology , Mice , Receptors, CXCR6/metabolism , Receptors, CXCR6/immunology , Programmed Cell Death 1 Receptor/metabolism , Signal Transduction/immunology , Cell Movement/immunology , Humans , Kidney/pathology , Kidney/immunology , Kidney/metabolism , Lymphocytes/immunology , Lymphocytes/metabolism , Receptors, Interleukin/metabolism , Receptors, Interleukin/immunology , Mice, Inbred C57BL , Kidney Diseases/immunology , Kidney Diseases/metabolism , Kidney Diseases/pathology , Immunity, Innate/immunology , Mice, Knockout , Intestinal Mucosa/immunology , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Intestines/immunology , Intestines/pathology
6.
Drug Dev Res ; 85(2): e22168, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38450796

ABSTRACT

Hypoxia has been reported to promote the proliferation and migration of thyroid cancer, while the special mechanism was still unclear. HIF-1α/carnitine palmitoyl-transferase 1A (CPT1A) was found to be associated with papillary thyroid carcinoma (PTC) but the biological role of CPT1A in PTC was not explored. The effects of hypoxia and carnitine palmitoyl-transferase 1A (CPT1A) expression on PTC cells were determined by cell counting kit-8 assay, detection of oxidative stress, inflammation response and mitochondrial membrane motential (MMP). Oil Red O staining and the detection of free fatty acids were performed to assess the status of lipid metabolism. Flow cytometric analysis was performed to assess cell apoptosis. Quantitative polymerase chain reaction (qPCR) and western blot analysis were applied to investigate the expressions of CPT1A and HIF-1α and the molecules involved cell function. The expressions of CPT1A and HIF-1α were significantly increased in PTC cells with or without hypoxia treatment. CPT1A overexpression or silencing promoted or inhibited cell viability, and hypoxia further repressed cell viability. In addition, CPT1A overexpression alleviates hypoxia-induced increased oxidative stress, inflammation response and elevated MMP. CPT1A overexpression enhanced palmitic acid-induced decreased cell growth, enhanced the metabolic capacity of free fatty acid and suppressed cell apoptosis. Animal experiments showed that CPT1A overexpression promoted PTC tumor growth, reduced lipid deposition, oxidative stress and inflammation, as well as enhancing cell function indicators. However, CPT1A silencing showed the opposite effects both in vitro and in vivo. Hypoxia induces the high expression of HIF-1α/CPT1A, thereby reprogramming the lipid metabolism of PTC cells for adapting the hypoxia environment, meanwhile inhibiting the cell damage and apoptosis caused by oxidative stress.


Subject(s)
Lipid Metabolism , Thyroid Neoplasms , Animals , Thyroid Cancer, Papillary/genetics , Oxidative Stress , Thyroid Neoplasms/genetics , Hypoxia , Inflammation , Fatty Acids , Carnitine
7.
Comb Chem High Throughput Screen ; 27(11): 1611-1628, 2024.
Article in English | MEDLINE | ID: mdl-38213143

ABSTRACT

BACKGROUND: Osteoporosis (OP) is an age-related skeletal disease. Kaempferol can regulate bone mesenchymal stem cells (BMSCs) osteogenesis to improve OP, but its mechanism related to disulfidptosis, a newly discovered cell death mechanism, remains unclear. OBJECTIVE: The study aimed to investigate the biological function and immune mechanism of disulfidptosis- related ribophorin I (RPN1) in OP and to experimentally confirm that RPN1 is the target for the treatment of OP with kaempferol. METHODS: Differential expression analysis was conducted on disulfide-related genes extracted from the GSE56815 and GSE7158 datasets. Four machine learning algorithms identified disease signature genes, with RPN1 identified as a significant risk factor for OP through the nomogram. Validation of RPN1 differential expression in OP patients was performed using the GSE56116 dataset. The impact of RPN1 on immune alterations and biological processes was explored. Predictive ceRNA regulatory networks associated with RPN1 were generated via miRanda, miRDB, and TargetScan databases. Molecular docking estimated the binding model between kaempferol and RPN1. The targeting mechanism of kaempferol on RPN1 was confirmed through pathological HE staining and immunohistochemistry in ovariectomized (OVX) rats. RESULTS: RPN1 was abnormally overexpressed in the OP cohort, associated with TNF signaling, hematopoietic cell lineage, and NF-kappa B pathway. Immune infiltration analysis showed a positive correlation between RPN1 expression and CD8+ T cells and resting NK cells, while a negative correlation with CD4+ naive T cells, macrophage M1, T cell gamma delta, T cell follicular helper cells, activated mast cells, NK cells, and dendritic cells, was found. Four miRNAs and 17 lncRNAs associated with RPN1 were identified. Kaempferol exhibited high binding affinity (-7.2 kcal/mol) and good stability towards the RPN1. The experimental results verified that kaempferol could improve bone microstructure destruction and reverse the abnormally high expression of RPN1 in the femur of ovariectomized rats. CONCLUSION: RPN1 may be a new diagnostic biomarker in patients with OP, and may serve as a new target for kaempferol to improve OP.


Subject(s)
Kaempferols , Molecular Docking Simulation , Osteoporosis , Kaempferols/pharmacology , Kaempferols/chemistry , Animals , Osteoporosis/drug therapy , Rats , Humans , Female , Rats, Sprague-Dawley , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Endoribonucleases/metabolism
8.
Adv Sci (Weinh) ; 11(13): e2307850, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38240457

ABSTRACT

Kidney fibrosis is a common fate of chronic kidney diseases (CKDs), eventually leading to renal dysfunction. Yet, no effective treatment for this pathological process has been achieved. During the bioassay-guided chemical investigation of the medicinal plant Wikstroemia chamaedaphne, a daphne diterpenoid, daphnepedunin A (DA), is characterized as a promising anti-renal fibrotic lead. DA shows significant anti-kidney fibrosis effects in cultured renal fibroblasts and unilateral ureteral obstructed mice, being more potent than the clinical trial drug pirfenidone. Leveraging the thermal proteome profiling strategy, cell division cycle 42 (Cdc42) is identified as the direct target of DA. Mechanistically, DA targets to reduce Cdc42 activity and down-regulates its downstream phospho-protein kinase Cζ(p-PKCζ)/phospho-glycogen synthase kinase-3ß (p-GSK-3ß), thereby promoting ß-catenin Ser33/37/Thr41 phosphorylation and ubiquitin-dependent proteolysis to block classical pro-fibrotic ß-catenin signaling. These findings suggest that Cdc42 is a promising therapeutic target for kidney fibrosis, and highlight DA as a potent Cdc42 inhibitor for combating CKDs.


Subject(s)
Diterpenes , Kidney Diseases , cdc42 GTP-Binding Protein , Animals , Mice , beta Catenin/drug effects , beta Catenin/metabolism , Fibrosis/drug therapy , Glycogen Synthase Kinase 3 beta/drug effects , Glycogen Synthase Kinase 3 beta/metabolism , Kidney/metabolism , Kidney Diseases/drug therapy , Wikstroemia/chemistry , Diterpenes/pharmacology , cdc42 GTP-Binding Protein/drug effects
9.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1025484

ABSTRACT

Objective:To describe and analyze suicide risk of patients with schizophrenia,major depressive disorder,and bipolar disorder.Methods:A total of 2 016 patients with schizophrenia,903 patients with major de-pressive disorder,and 381 patients with bipolar disorder from inpatients,clinics,or communities who met the diag-nostic criteria of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition were recruited.All patients were interviewed by psychiatrists using the Mini International Neuropsychiatric Interview to diagnose mental disor-ders and assess suicide risk,as well as Clinical-Rated Dimensions of Psychosis Symptom Severity(CRDPSS)to as-sess symptoms.Differences and risk factors of suicide risk among three types of mental disorders were explored u-sing multivariate logistic regression analysis.Results:In the past one month,37 patients with schizophrenia(1.8%),516 patients with major depressive disorder(57.1%),and 102 patients with bipolar disorder(26.8%)had suicide risk.Compared with patients with schizophrenia,suicide risk in patients with major depressive disorder(OR=36.50)and bipolar disorder(OR=20.10)increased.Female(OR=1.87),smoking(OR=1.76),family history of suicide(OR=5.09),higher score of CRDPSS hallucination(OR=1.80),and higher score of CRDPSS depression(OR=1.54)were risk factors of suicide risk of patients.Conclusions:Suicide risk of patients with ma-jor depressive disorder and bipolar disorder is higher than that of patients with schizophrenia.In clinical practice,it is important to regularly assess suicide risk of patients.Patients who experience symptoms of hallucination and de-pression should be paid more attention to.

10.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1025485

ABSTRACT

Objective:To evaluate direct and indirect costs for schizophrenia,major depressive disorder(MDD)and bipolar disorder,and to compare their differences of cost composition,and to explore the drivers of the total costs.Methods:A total of 3 175 inpatients with schizophrenia,MDD,and bipolar disorder were recruited.In-patient's self-report total direct of medical costs outpatient and inpatient,out-of-pocket costs,and direct non-medical costs were regarded as direct costs.Productivity loss and other loss caused by damaging properties were defined as indirect costs.The perspectives of this study included individual and societal levels.Multivariate regression analysis was applied for detecting the factors influencing disease costs.Results:The total cost of schizophrenia was higher than those of MDD and bipolar disorder at individual and societal levels.The indirect costs of three mental disorders were higher than the direct costs,and the indirect cost ratio of bipolar disorder was higher than those of schizophre-nia and MDD.Age,gender,working condition and marital status(P<0.05)were the important drivers of total costs.Conclusion:The economic burden of the three mental disorders is relatively heavy.Schizophrenia has heaviest disease burden,and the productivity loss due to mental disorders is the driving force of the soaring disease cost

11.
Chinese Mental Health Journal ; (12): 25-32, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1025487

ABSTRACT

Objective:To describe demographic,clinical and physiological characteristics,treatment between first-episode major depressive disorder(MDD)and relapse MDD,and to explore characteristics of relapse MDD.Methods:Totally 858 patients who met the diagnostic criteria for depression of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5),were included by using the Mini International Neuropsychiatric Interview(MINI),Clinician-Rated Dimensions of Psychosis Symptom Severity,and Hamilton Depression Scale etc.Among them,529(58.6%)were first-episode depression and 329(36.0%)were relapsed.The differences of demographic characteristics,clinical and physiological characteristics,treatment were compared byx2test and Kruskal-Wallis rank sum test.Multivariate logistic regression was used to explore the characteristics of MDD recur-rence.Results:Compared to first-episode MDD,relapse MDD had more comorbidity(OR=2.11,95%CI:1.00-4.44),more days out of role(OR=1.26,95%CI:1.01-1.56),more history of using psychiatric drug more than one month(OR=1.41,95%CI:1.02-1.97)and electroconvulsive therapy(OR=3.23,95%CI:1.42-7.36),and higher waist-hip ratio(OR=33.88,95%CI:2.88-399.32).Conclusion:Relapse MDD has positive as-sociation with comorbidity of mental disorders,out of role,and higher waist-hip ratio.

12.
Chinese Mental Health Journal ; (12): 33-41, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1025488

ABSTRACT

Objective:To compare demographic characteristics,clinical characteristics,therapeutic characteris-tics and physiological indicators of patients with bipolar Ⅰ disorder and bipolar Ⅱ disorder.Methods:A total of 381 patients with bipolar disorder(BD)diagnosed by the Diagnostic and Statistical Manual of Mental Disorders 5 th Edi-tion(DSM-5)were selected,including 302 patients with BD-Ⅰ(79.27%),74 patients with BD-Ⅱ(19.42%)and 5 patients with other specific and related disorders(1.31%).Demographic and clinical characteristics were collected with self-designed clinical information questionnaire.Multivariate logistic regression and multivariate linear regres-sion analysis were used for analysis.Results:Compared with patients with BD-Ⅱ,patients with BD-Ⅰ had more risk to have psychotic features(OR=5.75,95%CI:2.82-11.76),longer disease duration,and more repeated transcra-nial magnetic therapy(OR=3.09,95%CI:1.02-9.35),higher uric acid,total cholesterol and high-density lipo-protein.BD-Ⅰ in Han nationality was more common(OR=11.50,95%CI:1.76-75.30),and had lower education level(OR=10.22,95%CI:1.16-89.77),and less family history of psychosis(OR=2.34,95%CI:1.01-5.42).Conclusion:There are significant differences between BD-Ⅰ and BD-Ⅱ in demographic and clinical charac-teristics,treatment status,and physiological indicators,which could provide clues for exploring the pathogenesis of bipolar disorder.

13.
Chinese Mental Health Journal ; (12): 42-49, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1025489

ABSTRACT

Objective:To compare clinical characteristics,treatment patterns and physiological indicators in bipolar disorder(BD)patients with different age of onset.Methods:Totally 380 patients with DSM-5 BD were se-lected in this study.Psychiatrists diagnosed the patients using the Mini International Neuropsychiatric Interview.The clinical information questionnaire and the Global Assessment of Functioning scale were utilized to collected clinical characteristics,treatment status,and physiological indicators.The onset age of BD was divided into 21 and 35 years as cut-off points.Multivariate logistic regression and linear regression were used to analyze related factors.Results:Among the 380 patients with BD,199 cases were early-onset group(52.4%),121 cases were middle-onset group(31.8%),and 60 cases were late-onset group(15.8%).There were 26.6%of patients in the early-onset group in-itially diagnosed as depression,23.1%in the middle-onset group,and 11.7%in the late-onset group.Multivariate analysis revealed that compared to the early-onset group of BD,the middle-onset(OR=2.22)and late-onset(OR=4.99)groups had more risk to experience depressive episodes,and the late-onset group(OR=6.74)had 6.74 times of risk to suffer from bipolar Ⅱ disorder.Additionally,patients in the middle-onset(β=-1.52)and late-on-set(β=-4.29)groups had shorter durations of delayed treatment,and those in the middle-onset(β=-1.62)and late-onset(β=-3.14)groups had fewer hospitalizations.Uric acid levels were lower in both the middle-onset(β=-28.39)and late-onset(β=-31.47)groups,and total cholesterol level was lower in the middle-onset group(β=-0.23).Conclusion:Patients with BD in different age of onset show significant differences in clinical charac-teristics,treatment conditions and physiological indicators.

14.
Journal of Chinese Physician ; (12): 360-365, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1026108

ABSTRACT

Objective:To explore the mechanism of Huangqi Jiedu Decoction (HQJD) in the treatment of breast cancer with the syndrome of Zheng deficiency and toxic incandescence by network pharmacology and molecular docking technology.Methods:The main active ingredients and targets of HQJD were screened through the traditional Chinese medicine (TCM) systematic pharmacology database and analysis platform. The relevant targets of breast cancer with the syndrome of Zheng-deficiency, toxic-incandescence were obtained using OMIM, GeneGards and Drugbank databases, and the relevant targets of HQJD for the treatment of breast cancer with the syndrome of Zheng-deficiency and toxic incandescence were obtained by intersection; The Cytoscape 3.9.1 software was used to build the protein protein interaction (PPI) network and the " drug active component target disease" network on the basis of String 11.0 database, and the core active components and core targets of HQJD in treating breast cancer with the syndrome of Zheng-deficiency and toxic-incandescence were inferred according to the topological parameters. gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on core targets using R language; and molecular docking verification on the main active ingredients and core targets were conducted.Results:230 effective targets of active ingredients of HQJD were screened, and 15 467 active ingredients of breast cancer with syndrome of Zheng-deficiency/toxic-incandescence were obtained; 217 intersection targets; GO function enrichment analysis showed that the treatment of HQJD for breast cancer with the syndrome of Zheng-deficiency and toxic-incandescence mainly involved oxidative stress and cytochemical stress; The enrichment analysis of KEGG pathway showed that HQJD treatment of breast cancer with the syndrome of Zheng-deficiency and toxic-incandescence was mainly related to phosphatidylinositol 3-protein kinase B (PI3K-Akt), interleukin-17 (IL-17) and other signal pathways. The molecular docking results showed that the main active ingredients such as β-sitosterol, stigmasterol, luteolin had good binding ability with core targets.Conclusions:HQJD has the characteristics of multi-component, multi target and multi pathway in the treatment of breast cancer with syndrome of Zheng-deficiency and toxic-incandescence, and its main mechanism may be related to PI3K-Akt, IL-17, P53 and other signal pathways.

15.
Sichuan Mental Health ; (6): 193-197, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1039248

ABSTRACT

With the implementation of the 'Mental Health Law of the People's Republic of China' and relevant policies, governments at all levels have devoted more resources to community-based rehabilitation services for patients with mental disorders, making the mental health services more accessible and professional to the majority of patients with mental disorders. Monumental achievements have been made in community-based rehabilitation services for patients with severe mental disorders, while challenges have always existed in the China's community mental health service system for patients with severe mental disorders. Therefore, this article elaborated the achievements, challenges and prospects of China's community mental health service system for patients with severe mental disorders, aiming to provide references for future work and further improve the quality and accessibility of community mental health service for patients with mental disorders.

16.
Adv Sci (Weinh) ; 10(35): e2302804, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37915129

ABSTRACT

Group 3 innate lymphoid cells (ILC3s) represent a new population in immune regulation, yet their role in lupus nephritis (LN) remains elusive. In the present work, systemic increases in ILC3s, particularly in the kidney, are observed to correlate strongly with disease severity in both human and murine LN. Using MRL/lpr lupus mice and a nephrotoxic serum-induced LN model, this study demonstrates that ILC3s accumulated in the kidney migrate predominantly from the intestine. Furthermore, intestinal ILC3s accelerate LN progression, manifested by exacerbated autoimmunity and kidney injuries. In LN kidneys, ILC3s are located adjacent to B cells within ectopic lymphoid structures (ELS), directly activating B cell differentiation into plasma cells and antibody production in a Delta-like1 (DLL1)/Notch-dependent manner. Blocking DLL1 attenuates ILC3s' effects and protects against LN. Altogether, these findings reveal a novel pathogenic role of ILC3s in B cell activation, renal ELS formation and autoimmune injuries during LN, shedding light on the therapeutic value of targeting ILC3s for LN.


Subject(s)
Lupus Nephritis , Humans , Animals , Mice , Lupus Nephritis/drug therapy , Lupus Nephritis/pathology , Immunity, Innate , Lymphocytes , Mice, Inbred MRL lpr , Kidney
17.
Horm Metab Res ; 55(12): 855-868, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37813352

ABSTRACT

This cohort study evaluated the associations of different treatments with the prognosis of follicular variant papillary thyroid carcinoma (FVPTC) and classical papillary thyroid carcinoma (CPTC) patients. The data of 69034 PTC patients were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. The 5-year mortality of CPTC and FVPTC patients receiving surgery, radiation and combination therapy were compared. The univariable and multivariable cox proportional risk models explored the associations between different treatments and the 5-year mortality in CPTC and FVPTC patients. The 5-year mortality of CPTC patients was 2.81% and FVPTC patients was 2.47%. Compared with CPTC receiving lobectomy and/or isthmectomy, those not receiving surgery were associated with increased risk of 5-year mortality [Hazards ratio (HR)=3.27, 95% confidence interval (CI): 2.55-4.20] while total thyroidectomy was correlated with reduced risk of 5-year mortality (HR=0.67, 95%CI: 0.55-0.80). Radioactive iodine (RAI) was linked with decreased risk of 5-year mortality in CPTC patients (HR=0.57, 95%CI: 0.50-0.65). CPTC patients undergoing both surgery and radiation were related to decreased risk of 5-year mortality compared with those receiving surgery only (HR=0.55, 95%CI: 0.48-0.63). CPTC patients receiving neither surgery nor radiation (HR=4.53, 95%CI: 3.72-5.51) or those receiving radiation (HR=1.98, 95%CI: 1.13-3.48) were correlated with elevated risk of 5-year mortality. The elevated risk of 5-year mortality in FVPTC patients was reduced in those undergoing RAI (HR=0.63, 95%CI: 0.51-0.76). In conclusion, combination therapy was associated with decreased risk of 5-year mortality in CPTC and FVPTC patients, which might provide a reference for the management of these patients.


Subject(s)
Thyroid Neoplasms , Humans , Thyroid Neoplasms/radiotherapy , Thyroid Neoplasms/surgery , Thyroid Cancer, Papillary/surgery , Cohort Studies , Iodine Radioisotopes/therapeutic use , Prognosis , Retrospective Studies
18.
Cardiovasc Diagn Ther ; 13(3): 609-622, 2023 Jun 30.
Article in English | MEDLINE | ID: mdl-37405018

ABSTRACT

Background and Objective: Apoptosis-inducing factor (AIF), a flavin protein in mitochondria, is originally found to induce apoptosis under the stimulation of pro-apoptotic factors. As a mitochondrial flavin adenine dinucleotide-dependent oxidoreductase, AIF is involved in the regulation of mammalian cell metabolism by regulating respiratory enzyme activity, antioxidant stress, promoting mitochondrial autophagy and glucose uptake, etc. Herein, we focused on the research progress regarding the molecular mechanism of AIF in metabolic mediation and the recent research on AIF in metabolic diseases, as well as the AIF-mediated apoptotic process. Methods: Articles for this paper were obtained by reviewing the literature related to the role of AIF in metabolic diseases on PubMed. The search terms included the following: "apoptosis", "metabolism" or "metabolic diseases" plus "apoptosis-inducing factor". The titles, abstracts, and full texts of relevant English-language publications published from October 1996 to June 2022 were manually screened to clarify the role of AIF in metabolic diseases. Key Content and Findings: We found that AIF played an important role in a variety of metabolically-related diseases, such as diabetes, obesity, metabolic syndrome, and tumor metabolism, by mediating apoptosis. Conclusions: We summarized the important role of AIF in a variety of metabolic diseases, which might help to further expand the understanding of AIF and to develop AIF-related therapeutic targets.

19.
Pediatr Infect Dis J ; 42(11): 942-948, 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-37523508

ABSTRACT

BACKGROUND: Chronic hepatitis B virus (HBV) infection burden in children remains a pressing public health concern. Whether antiviral therapy should be administered to children with HBV in the immune-tolerant phase remains controversial. We performed a meta-analysis to evaluate antiviral therapy efficacy and safety in children with immune-tolerant hepatitis B (ITHB). METHODS: A search was conducted in multiple databases (PubMed, Embase, Cochrane, Web of Science, CBM, CNKI and Wanfang Data) to identify clinical trials examining antiviral therapy efficacy and safety in children (1-18 years) with ITHB viral infection from inception to February 2023. Outcomes were calculated separately for controlled and single-arm studies. RESULTS: Nine trials (442 patients), including 2 randomized controlled trials (RCTs), 3 non-RCTs and 4 single-arm studies, were included in this meta-analysis. In the RCTs, antiviral therapy group exhibited greater rates of HBsAg loss [risk ratio (RR) = 6.11, 95% confidence interval (CI): 1.67-22.31, P Z-test = 0.006], HBsAg serologic response (RR = 5.29, 95% CI: 1.47-19.07, P Z-test = 0.011) and HBeAg loss (RR = 3.00, 95% CI: 1.35-6.66, P Z-test = 0.007) compared with the control group at the end of follow-up. In single-arm studies, the pooled incidences of HBsAg loss, HBeAg loss and HBsAg seroconversion were 24% (95% CI: -0.1% to 48%), 24% (95% CI: -0.1% to 48%) and 24% (95% CI: -5% to 52%), respectively. CONCLUSION: Current evidence suggests the effectiveness of antiviral therapy in children with HBV infection in the immune-tolerant stage, with few serious adverse events. Due to the limited quality and number of included studies, more high-quality studies are required to validate our findings.

20.
Mol Immunol ; 158: 103-106, 2023 06.
Article in English | MEDLINE | ID: mdl-37182441

ABSTRACT

OBJECTIVE: To explore the differences in type I hypersensitivity-induced inflammatory response among children of different age groups with acute appendicitis. METHODS: We selected children diagnosed with "acute appendicitis" who underwent surgery in the Department of General Surgery of Anhui Provincial Children's Hospital from January 2022 to June 2022 and collected their basic data. We divided them into two groups according to age: the infant group (less than 3 years old) and the pediatric group (3-14 years old). The gender, age, onset time, hospital stay, preoperative white blood cells, percentage of neutrophils, C-reactive protein (CRP), and enzyme-linked immunosorbent assay (ELISA) were collected to determine the levels of immunoglobulin E (IgE), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-6 (IL-6), and interleukin-9 (IL-9) in appendicular lavage fluid, and the differences between the two groups were compared. RESULTS: There were 15 children in the infant group and 15 in the pediatric group. There was no significant difference between the two groups with respect to onset time and gender. The hospitalization time in the pediatric group was (5.7 ± 2.1) d, the preoperative white blood cells were (14.3 ± 3.7) × 10^9/mL, neutrophil percentage was (84.5 ± 6.3)%, and CRP was (20.0 ± 17.9) mg/mL. The hospitalization time of the infant group was (8.0 ± 3.1) d, the preoperative white blood cells were (19.0 ± 3.8) × 10^9/mL, neutrophil percentage was (77.8 ± 10.4)%, and CRP was (42.5 ± 25.0) mg/mL. The differences between the two groups were significant. There was no significant difference in IL-5 concentration between the two groups in the appendicular lavage fluid. IgE (610.74 ± 72.56) ng/mL, IL-4 (30.80 ± 12.04) ng/mL, IL-6 (118.09 ± 14.29) ng/mL, IL-9 (133.94 ± 16.00) ng/mL were found in the infant group, and IgE (495.61 ± 95.09) ng/mL, IL-4 (22.68 ± 7.05) ng/mL, IL-6 (98.22 ± 22.18) ng/mL and IL-9 (107.86 ± 27.34) ng/mL were found in the pediatric group, and the differences between the two groups were statistically significant. CONCLUSIONS: The inflammatory response in children with acute appendicitis was associated with type I hypersensitivity-induced inflammatory responses, and the type I hypersensitivity was more intense in children in the lower age group.


Subject(s)
Appendicitis , Hypersensitivity, Immediate , Hypersensitivity , Infant , Humans , Child , Child, Preschool , Adolescent , Interleukin-4 , Interleukin-9 , Interleukin-5 , Interleukin-6 , Appendicitis/surgery , Appendicitis/diagnosis , C-Reactive Protein/metabolism , Acute Disease , Immunoglobulin E
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