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1.
Front Oncol ; 14: 1408524, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38846972

RESUMO

The incidence of leiomyosarcoma (LMS) is about 4-5/100,000 individuals per year. LMSs occurring in the small bowel are even rarer, and their preoperative diagnosis is very difficult. We described two patients with pathologically confirmed small bowel LMS and analyzed their clinical and medical imaging features. Similar cases reported in English in Pubmed database over the past decade were reviewed and summarized. These tumors were categorized by the growth direction and relationship with the intestinal lumen into three types: intraluminal (n = 10), intermural (n = 3), and extraluminal (n = 7). Notably, among the three types of LMS, the intramural leiomyosarcoma stands out as a noteworthy subtype. Emerging evidence suggests that smaller tumor size (< 5 cm) and the intraluminal type may serve as favorable prognostic indicators, while the extraluminal type is associated with relatively poor prognosis. Furthermore, the integration of imaging features with CA125 and LDH biomarkers holds promise for potential diagnostic value in LMS.

2.
Chem Sci ; 15(24): 9318-9324, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38903240

RESUMO

The global demand for poly-grade ethylene (C2H4) is increasing annually. However, the energy-saving purification of this gas remains a major challenge due to the similarity in molecular properties among the ternary C2 hydrocarbons. To address this challenge, we report an approach of systematic tuning of the pore environment with organic sites (from -COOH to -CF3, then to -CH3) in porous coordination polymers (PCPs), of which NTU-73-CH3 shows remarkable capability for the direct production of poly-grade C2H4 from ternary C2 hydrocarbons under ambient conditions. In comparison, the precursor structure of NTU-73-COOH is unable to purify C2H4, while NTU-73-CF3 shows minimal ability to harvest C2H4. This is because the changed binding sites in the NTU-73-series not only eliminate the channel obstruction caused by the formation of gas clusters, but also enhance the interaction with acetylene (C2H2) and ethane (C2H6), as validated by in situ crystallographic and Raman analysis. Our findings, in particular the systematic tuning of the pore environment and the efficient C2H4 purification by NTU-73-CH3, provide a blueprint for the creation of advanced porous families that can handle desired tasks.

3.
J Hepatocell Carcinoma ; 11: 747-766, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38680213

RESUMO

Purpose: Nonsense-mediated RNA decay (NMD), a surveillance pathway for selective degradation of aberrant mRNAs, is associated with cancer progression. Its potential as a predictor for aggressive hepatocellular carcinoma (HCC) is unclear. Here, we present an innovative NMD risk model for predicting HCC prognosis. Methods: The Cancer Genome Atlas (TCGA) data of 374 liver HCC (LIHC) and 50 normal liver samples were extracted. A risk model based on NMD-related genes was developed through least absolute shrinkage and selection operator Cox (LASSO-Cox) regression of the LIHC-TCGA data. Prognostic validation was done using GSE54236, GSE116174, and GSE76427 data. Univariate and multivariate Cox regression analyses were conducted to assess the prognostic value of the model. We also constructed nomograms for survival prediction. Tumor immune infiltration was evaluated using the CIBERSORT algorithm, and the tumor cell phenotype was assessed. Finally, mouse experiments verified UPF3B knockdown effects on HCC tumor characteristics. Results: We developed a risk model based on four NMD-related genes (PABPC1, RPL8, SMG5, and UPF3B) and validated it using GSE54236, GSE116174, and GSE76427 data. The model effectively distinguished high- and low-risk groups corresponding to unfavorable and favorable HCC outcomes. Its prognostic prediction accuracy was confirmed through time-dependent ROC analysis, and clinical-use nomograms with calibration curves were developed. Single-cell RNA sequencing results indicated significantly higher expression of SMG5 and UPF3B in tumor cells. Knockdown of SMG5 and UPF3B inhibited HCC cell proliferation, invasion, and migration, while affecting cell-cycle progression and apoptosis. In vivo, UPF3B knockdown delayed tumor growth and increased immune cell infiltration. Conclusion: Our NMD-related gene-based risk model can help identify therapeutic targets and biomarkers for HCC. Additionally, it assists clinicians in predicting the prognosis of HCC patients.

4.
Hortic Res ; 11(4): uhae040, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38623073

RESUMO

The gaseous plant hormone ethylene regulates plant development, growth, and responses to stress. In particular, ethylene affects tolerance to salinity; however, the underlying mechanisms of ethylene signaling and salt tolerance are not fully understood. Here, we demonstrate that salt stress induces the degradation of the ethylene receptor ETHYLENE RESPONSE 3 (RhETR3) in rose (Rosa hybrid). Furthermore, the TspO/MBR (Tryptophan-rich sensory protein/mitochondrial benzodiazepine receptor) domain-containing membrane protein RhTSPO interacted with RhETR3 to promote its degradation in response to salt stress. Salt tolerance is enhanced in RhETR3-silenced rose plants but decreased in RhTSPO-silenced plants. The improved salt tolerance of RhETR3-silenced rose plants is partly due to the increased expression of ACC SYNTHASE1 (ACS1) and ACS2, which results in an increase in ethylene production, leading to the activation of ETHYLENE RESPONSE FACTOR98 (RhERF98) expression and, ultimately accelerating H2O2 scavenging under salinity conditions. Additionally, overexpression of RhETR3 increased the salt sensitivity of rose plants. Co-overexpression with RhTSPO alleviated this sensitivity. Together, our findings suggest that RhETR3 degradation is a key intersection hub for the ethylene signalling-mediated regulation of salt stress.

5.
Biochem Biophys Res Commun ; 700: 149535, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38308909

RESUMO

To compare the merits and drawbacks of three approaches for establishing a rabbit model of nonobstructive coronary microcirculatory disease, namely, open thoracic subtotal ligation of coronary arteries, ultrasound-guided cardiac microsphere injection, and sodium laurate injection. New Zealand rabbits were allocated to four groups: a normal group (Blank group), an Open-chest group (Open-chest), a microsphere group (Echo-M), and a sodium laurate group (Echo-SL), each comprising 10 rabbits. The rabbits were sacrificed 24 h after the procedures, and their echocardiography, stress myocardial contrast echocardiography, pathology, and surgical times were compared. The results demonstrated varying degrees of reduced cardiac function in all three experimental groups, the Open-chest group exhibiting the most significant decline. The myocardial filling in the affected areas was visually analyzed by myocardial contrast echocardiography, revealing sparse filling at rest but more after stress. Quantitative analysis of perfusion parameters (ß, A, MBF) in the affected myocardium showed reduced values, the Open-chest group having the most severe reductions. No differences were observed in stress myocardial acoustic imaging parameters between the Echo-M and Echo-SL groups. Among the pathological presentations, the Open-chest model predominantly exhibited localized ischemia, while the Echo-M model was characterized by mechanical physical embolism, and the Echo-SL model displayed in situ thrombosis as the primary pathological feature. Inflammatory responses and collagen deposition were observed in all groups, with the severity ranking of Open-chest > Echo-SL > Echo-M. The ultrasound-guided intracardiac injection method used in this experiment outperformed open-chest surgery in terms of procedural efficiency, invasiveness, and maneuverability. This study not only optimizes established cardiac injection techniques but also offers valuable evidence to support clinical investigations through a comparison of various modeling methods.


Assuntos
Doença da Artéria Coronariana , Circulação Coronária , Coelhos , Animais , Microcirculação , Circulação Coronária/fisiologia , Miocárdio/patologia
6.
Int J Nurs Knowl ; 35(2): 117-129, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36843066

RESUMO

PURPOSE: Breast cancer is the most common cancer type worldwide, with its survivors often experiencing physical and psychosocial health problems. Wearable device use is an innovative and effective way to promote physical activity and improve health-related outcomes in breast cancer survivors; however, the current evidence is unclear. We aimed to determine the effects of wearable devices on physical activity and health-related outcomes in breast cancer survivors. METHODS: PubMed, Embase, Web of Science, and Cochrane Library databases were searched to identify eligible studies from inception to September 2022. Additional relevant studies were obtained from the reference lists of the identified studies. Two reviewers independently screened the eligible studies, appraised the risk of bias, and extracted the data. Meta-analysis was conducted using Review Manager version 5.3. FINDINGS: Sixteen randomized controlled trials were included. Physical activity tracking and pedometer-based interventions improved moderate-intensity physical activity (standardized mean difference [SMD] = 0.32, 95% confidence interval [CI]: 0.17-0.46, p < 0.0001), moderate-to-vigorous physical activity (SMD = 0.85, 95%CI: 0.38-1.32, p = 0.0004), total physical activity (SMD = 0.51, 95%CI: 0.12-0.90, p = 0.01), quality of life (SMD = 0.17, 95%CI: 0.03-0.31, p = 0.01), physical function (SMD = 0.21, 95%CI: 0.04-0.38, p = 0.02), and mood state profiles (SMD = -0.58, 95%CI: -1.13 to 0.02, p = 0.04) in breast cancer survivors. However, the effects of low-intensity physical activity, vigorous-intensity physical activity, fatigue, anxiety, depression, and sleep quality could not be ascertained. CONCLUSIONS: Physical activity tracking and pedometer-based interventions were effective in increasing physical activity and improving health-related outcomes in breast cancer survivors. IMPLICATIONS FOR NURSING PRACTICE: This review offers availability of credible evidence supporting the potential usefulness and effectiveness of wearable physical activity trackers on physical activity and health-related outcomes in breast cancer survivors.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Dispositivos Eletrônicos Vestíveis , Humanos , Feminino , Qualidade de Vida , Depressão , Exercício Físico , Sobreviventes
7.
Front Physiol ; 14: 1279423, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38033331

RESUMO

Background: The role of the Wnt pathway in bone and its targets in skeletal disease has garnered interest, but the field lacks a systematic analysis of research. This paper presents a bibliometric study of publications related to the Wnt signaling pathway in bone to describe the current state of study and predict future outlooks. Methods: All relevant articles and reviews from 1993 to 2022 were collected from the Web of Science Core Collection (WoSCC). Bibliometric analysis and visualization were performed using CiteSpace 6.1 R3, VOSviewer 1.6.15, and the Online Analysis Platform of Literature Metrology (http://bibliometric.com/). Results: A total of 7,184 papers were retrieved, authored by 28,443 researchers from 89 countries/regions and published in 261 academic journals. The annual publication numbers peaked in 2021. China and United States are the leading countries, with the University of California and Harvard University as the most active institutions. Wang, Yang is the most prolific author. Bone has the most published research, while Proceedings of the National Academy of Sciences of the United States is the most cited journal on average. The main keywords include expression, Wnt, osteoporosis, bone, and osteogenic differentiation. Current and developing research hotspots focus on bone mass, sclerostin antibody, multiple myeloma, and cartilage development. Conclusion: This paper provides new insights for researchers to delve into the mechanisms of Wnt and bone related diseases and translate into clinical studies. It reveals the development and future research trends in Wnt and skeletal-related studies.

8.
J Pharm Pharmacol ; 75(12): 1496-1508, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-37897405

RESUMO

OBJECTIVES: To explore the effect of extract of Styrax (ES) on myocardial ischemic injury and its molecular mechanism, indirectly providing a theoretical basis for the development of ES. METHODS: In order to assess the impact of ES treatment on ischemic heart disease, both a left anterior descending ligation-induced myocardial infarction (MI) model and an ischemia/hypoxia (I/H)-induced H9c2 cell injury model have been constructed. Specifically, Sprague-Dawley rats were randomly assigned to the following groups (n = 8) and administered intragastrically once a day for seven consecutive days: Sham group, MI group, ES-L (0.2 g/kg) group, ES-M (0.4 g/kg) group, ES-H (0.8 g/kg) group, and trimetazidine (TMZ, 0.02 g/kg) group. The cardiac functions and biochemical assessment of rats were detected. Then, we validated experimentally the targets and mechanism of ES on these pathological processes in I/H-induced H9c2 cell injury model. KEY FINDINGS: These results showed that different doses of ES (0.2 g/kg, 0.4 g/kg, 0.8 g/kg, intragastric) significantly improved myocardial structure and function when compared to the MI group. The results of 2,3,5-triphenyltetrazolium chloride (TTC), hematoxylin-eosin, and masson staining indicated that ES could significantly reduce infarct size, inhibit myocardium apoptosis, and decrease myocardial fibrosis. Moreover, ES distinctly suppressed the serum levels of lactate dehydrogenase (LDH), cardiac troponin T (cTnT), and creatine kinase-MB (CK-MB), alleviated myocardial mitochondrial morphology, and stimulated adenosine triphosphate (ATP) production, increased the level of succinate dehydrogenase (SDH), complex I and complex V activity. Different doses of ES (5 µg/ml, 10 µg/ml, 20 µg/ml) also improved cardiomyocyte morphology and decreased the apoptosis rate in H9c2 cells that had been exposed to I/H. Furthermore, the results of western blotting and qRT-PCR indicated that ES promoted the expression of proteins and mRNA related to energy metabolism, including phosphorylated adenosine monophosphate activated protein kinase (p-AMPK), peroxisome proliferator activated receptor gamma coactivator 1 alpha (PCG-1α), nuclear respiratory factor 1, and mitochondrial transcription factor A (TFAM). Mechanically, after the administration of Compound C (dorsomorphin), an AMPK inhibitor, these effects of myocardial protection produced by ES were reversed. CONCLUSIONS: Collectively, these results demonstrated that ES could improve myocardial mitochondrial function and reduce ischemic injury by activating AMPK/PCG-1α signaling pathway, while indicating its potential advantages as a dietary supplement.


Assuntos
Proteínas Quinases Ativadas por AMP , Liquidambar , Ratos , Animais , Proteínas Quinases Ativadas por AMP/metabolismo , Liquidambar/metabolismo , Styrax/metabolismo , Ratos Sprague-Dawley , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Miócitos Cardíacos , Transdução de Sinais , Mitocôndrias , Isquemia/metabolismo
9.
Zhongguo Zhen Jiu ; 43(10): 1118-22, 2023 Oct 12.
Artigo em Chinês | MEDLINE | ID: mdl-37802516

RESUMO

OBJECTIVE: To observe the effect of acupuncture exercise therapy synchronizing isokinetic muscle strength training on the motor function, stability and proprioception of knee joint, as well as the anxiety emotion in patients after meniscectomy under arthroscopy. METHODS: A total of 70 patients after meniscectomy under arthroscopy were randomized into an observation group (35 cases, 2 cases were eliminated, 2 cases dropped off) and a control group (35 cases, 2 cases were eliminated, 1 case dropped off). Acupuncture was applied at Chize (LU 5), Neixiyan (EX-LE 4), Dubi (ST 35),Yanglingquan (GB 34), etc. on the affective side in the two groups. After 30 min, the needles of the knee joint area were withdrew, while the needle at elbow was continuously retained, the observation group was given acupuncture exercise therapy synchronizing isokinetic muscle strength training, and the control group was given conventional acupuncture exercise therapy. The treatment was given once a day, 7-day treatment was taken as one course, and totally 4 courses were required in the two groups. Before and after treatment, the knee joint Lysholm score, the knee joint isokinetic muscle strength flexion/extension ratio (H/Q), joint position sense measurement (JPS) and Hamilton anxiety scale (HAMA) score were compared in the two groups. RESULTS: After treatment, the knee joint Lysholm scores and H/Q were increased compared with those before treatment in the two groups (P<0.001), and the knee joint Lysholm score and H/Q in the observation group were higher than those in the control group (P<0.001); the JPS and HAMA scores were decreased compared with those before treatment in the two groups (P<0.001), the JPS and HAMA score in the observation group were lower than those in the control group (P<0.05). CONCLUSION: Acupuncture exercise therapy synchronizing isokinetic muscle strength training can effectively improve the motor function, stability and proprioception of knee joint, as well as the anxiety emotion in patients after meniscectomy under arthroscopy.


Assuntos
Terapia por Acupuntura , Osteoartrite do Joelho , Treinamento Resistido , Humanos , Artroscopia , Meniscectomia , Resultado do Tratamento , Osteoartrite do Joelho/terapia , Terapia por Exercício , Músculos , Força Muscular , Pontos de Acupuntura
10.
Pharm Biol ; 61(1): 1318-1331, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37621078

RESUMO

CONTEXT: Styrax is used for prevention and treatment of cerebrovascular diseases. However, the underlying mechanism remains unclear. OBJECTIVE: To elucidate styrax's anti-ischemic stroke protective effects and underlying mechanisms. MATERIALS AND METHODS: An ischemic-stroke rat model was established based on middle cerebral artery occlusion (MCAO). Sprague-Dawley rats were randomly assigned to the following groups (n = 10) and administered intragastrically once a day for 7 consecutive days: sham, model, nimodipine (24 mg/kg), styrax-L (0.1 g/kg), styrax-M (0.2 g/kg) and styrax-H (0.4 g/kg). Neurological function, biochemical assessment, and ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS)-based serum metabonomics were used to elucidate styrax's cerebral protective effects and mechanisms. Pearson correlation and western blot analyses were performed to verify. RESULTS: The addition of 0.4 g/kg styrax significantly reduced cerebral infarct volume and neurobehavioral abnormality score. Different doses of styrax also decrease MDA, TNF-α, IL-6, and IL-1ß, and increase SOD and GSH-Px in ischemic-stroke rats (p < 0.05; MDA, p < 0.05 only at 0.4 g/kg dose). Biochemical indicators and metabolic-profile analyses (PCA, PLS-DA, and OPLS-DA) also supported styrax's protective effects. Endogenous metabolites (22) were identified in ischemic-stroke rats, and these perturbations were reversible via styrax intervention, which is predominantly involved in energy metabolism, glutathione and glutamine metabolism, and other metabolic processes. Additionally, styrax significantly upregulated phosphorylated AMP-activated protein kinase and glutaminase brain-tissue expression. CONCLUSION: Styrax treatment could ameliorate ischemic-stroke rats by intervening with energy metabolism and glutamine metabolism. This can help us understand the mechanism of styrax, inspiring more clinical application and promotion.


Assuntos
AVC Isquêmico , Styrax , Ratos , Animais , Ratos Sprague-Dawley , Glutamina , Metabolômica , Glutationa
11.
Biochim Biophys Acta Rev Cancer ; 1878(4): 188926, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37230421

RESUMO

Bladder cancer (BC) has high morbidity and mortality rates owing to challenges in clinical diagnosis and treatment. Advanced BC is prone to recurrence after surgery, necessitating early diagnosis and recurrence monitoring to improve the prognosis of patients. Traditional detection methods for BC include cystoscopy, cytology, and imaging; however, these methods have drawbacks such as invasiveness, lack of sensitivity, and high costs. Existing reviews on BC focus on treatment and management and lack a comprehensive assessment of biomarkers. Our article reviews various biomarkers for the early diagnosis and recurrence monitoring of BC and outlines the existing challenges associated with their application and possible solutions. Furthermore, this study highlights the potential application of urine biomarkers as a non-invasive, inexpensive adjunctive test for screening high-risk populations or evaluating patients with suspected BC symptoms, thereby alleviating the discomfort and financial burden associated with cystoscopy and improving patient survival.


Assuntos
Biomarcadores Tumorais , Neoplasias da Bexiga Urinária , Humanos , Biomarcadores Tumorais/genética , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/cirurgia , Cistoscopia/métodos , Fatores de Risco , Diagnóstico Precoce
12.
Front Aging Neurosci ; 15: 1102762, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37056689

RESUMO

Background: This study explored the mediating role of glucose homeostasis indicators in the relationship between serum cystatin C and mild cognitive impairment (MCI). Methods: The present study used a cross-sectional design and included 514 participants aged ≥50 years in Beijing, China. The Mini-Mental State Examination was used to assess cognitive function. Serum cystatin C and a comprehensive set of glucose homeostasis indicators were detected, including fasting blood glucose (FBG), glycosylated albumin percentage (GAP), glycated hemoglobin (HbAlc), insulin, and homeostatic model assessment of insulin resistance (HOMA-IR), and beta cell function (HOMA-ß). Generalized linear models were used to investigate the associations among cystatin C, glucose homeostasis indicators, and cognitive function. Mediation analysis was conducted to explore potential mediator variables. Results: In this study of 514 participants, 76 (14.8%) had MCI. Those with cystatin C levels ≥1.09 mg/L had a 1.98-fold higher risk of MCI than those with levels <1.09 mg/L (95% CI, 1.05-3.69). FBG, GAP, and HbA1c increased the risk of MCI, while HOMA-ß decreased the risk. Notably, the associations between MCI risk and cystatin C or glucose homeostasis were only founded in diabetes patients. Serum cystatin C was found to be positively associated with HOMA-ß (beta (95% CI): 0.20 [0.06, 0.34]), HOMA-IR (0.23 [0.09, 0.36]), and insulin (0.22 [0.09, 0.34]) levels. Moreover, HOMA-ß was identified as playing a negative mediating role (proportion mediated: -16%) in the relationship between cystatin C and MCI. Conclusion: Elevated levels of cystatin C are associated with an increased risk of MCI. The glucose homeostasis indicator, HOMA-ß, plays a negative mediating role in the relationship between cystatin C and MCI risk.

13.
Thromb Haemost ; 123(2): 192-206, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36126948

RESUMO

Platelets are produced from mature megakaryocytes which undergo polyploidization and proplatelet formation. Cell-cycle regulation plays a crucial role in megakaryocyte terminal differentiation especially in polyploidization. Dual-specificity tyrosine phosphorylation-regulated kinase 1B (DYRK1B) controls cell-cycle progression in cancer cells. The objective of this study was to determine DYRK1B function in megakaryocyte maturation and platelet production. A DYRK1B knock-out mouse was generated with increased peripheral platelet count compared with the wild type mouse without affecting megakaryocyte numbers in bone marrow. Polyploidy and proplatelet formations were significantly enhanced when DYRK1B was depleted in vitro. DYRK1B inhibition promoted megakaryocyte maturation by simultaneously upregulating cyclin D1 and downregulating P27. Furthermore, there was platelet restoration in two mice disease models of transient thrombocytopenia. In summary, DYRK1B plays an important role in megakaryocyte maturation and platelet production by interacting with cyclin D1 and P27. DYRK1B inhibition has potential therapeutic value in transient thrombocytopenia treatment. Graphic Abstract.


Assuntos
Megacariócitos , Trombocitopenia , Camundongos , Animais , Megacariócitos/metabolismo , Ciclina D1/metabolismo , Fosforilação , Plaquetas/metabolismo , Tirosina
14.
J Am Heart Assoc ; 11(24): e027228, 2022 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-36515244

RESUMO

Background Myocardial infarction (MI) is characterized by the emergence of dead or dying cardiomyocytes and excessive immune cell infiltration after coronary vessel occlusion. However, the complex transcriptional profile, pathways, cellular interactome, and transcriptional regulators of immune subpopulations after MI remain elusive. Methods and Results Here, male C57BL/6 mice were subjected to MI surgery and monitored for 1 day and 7 days, or sham surgery for 7 days, then cardiac CD45-positive immune cells were collected for single-cell RNA sequencing to determine immune heterogeneity. A total of 30 135 CD45+ immune cells were partitioned into macrophages, monocytes, neutrophils, dendritic cells, and T or B cells for further analysis. We showed that macrophages enriched for Olr1 and differentially expressed Gpnmb represented 2 crucial ischemia-associated macrophages with distinct proinflammatory and prophagocytic capabilities. In contrast to the proinflammatory subset of macrophages enriched for Olr1, Gpnmb-positive macrophages exhibited higher phagocytosis and fatty acid oxidation preference, which could be abolished by etomoxir treatment. In addition to macrophages, MI triggered prompt recruitment of neutrophils into murine hearts, which constituted the sequential cell-fate from naïve S100a4-positive, to activated Sell-high, to aging Icam1-high neutrophils. In silico tools predicted that the excessively expanded neutrophils at 1 day were attributed to chemokine C-C motif ligand/chemokine C-X-C motif ligand pathways, whereas CD80/inducible T-cell costimulator (ICOS) signaling was responsible for the immunosuppressive response at day 7 after MI. Finally, the Fos/AP-1 (activator protein 1) regulon was identified as the critical regulator of proinflammatory responses, which was significantly activated in patients with dilated cardiomyopathy and ischemic cardiomyopathy. We showed the enriched Fos/AP-1 target gene loci in genome-wide association study signals for coronary artery diseases and MI. Targeting Fos/AP-1 with the selective inhibitor T5224 blunted leukocyte infiltration and alleviated cardiac dysfunction in the preclinical murine MI model. Conclusions Taken together, this single-cell RNA sequencing data lay the groundwork for the understanding of immune cell heterogeneity and dynamics in murine ischemic hearts. Moreover, Fos/AP-1 inhibition mitigates inflammatory responses and cardiac dysfunction, which might provide potential therapeutic benefits for heart failure intervention after MI.


Assuntos
Infarto do Miocárdio , Miocárdio , Masculino , Camundongos , Animais , Miocárdio/metabolismo , Estudo de Associação Genômica Ampla , Ligantes , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismo , Fator de Transcrição AP-1/uso terapêutico , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/tratamento farmacológico , Quimiocinas/metabolismo , Modelos Animais de Doenças
15.
Pediatr Investig ; 6(3): 156-162, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36203522

RESUMO

Importance: There are a variety of musculoskeletal malformations and injuries that can occur in newborns. These can be a significant cause of perinatal death or a reason for miscarriage and can lead to long-term functional issues if not managed appropriately. There is no systematic and well-established screening program for neonatal musculoskeletal malformations and injuries in China now. Objective: To report the incidence and types of congenital musculoskeletal malformations in two hospitals in Shenzhen City, to explore and discuss the details of the screening procedure and improve future prevention and treatment. Methods: From October 2013 to May 2014, 2564 one-day-old newborns were screened by a pediatric orthopedic physical examination, in combination with ultrasonography when required, and the incidence and variety of diseases were recorded statistically. Results: Among 2564 screened newborns, the following musculoskeletal conditions were identified: congenital muscular torticollis (CMT) (seven cases, 0.27%), hip subluxation (four cases, 0.16%), hip dysplasia (47 cases, 1.83%), congenital talipes equinovarus (CTEV) (two cases, 0.08%), congenital talipes calcaneovalgus (15 cases, 0.58%), polydactyly (nine cases, 0.35%), syndactyly (one case, 0.04%), and spinal hemivertebra (one case, 0.04%). Additionally, there were five (0.19%) neonates with birth injuries. Interpretation: It is feasible to carry out neonatal screening and identification of musculoskeletal malformations and birth injuries in China. This is helpful as timely detection and early intervention for many of these conditions can avoid permanent functional impairment in these children.

16.
BMC Musculoskelet Disord ; 23(1): 892, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36183061

RESUMO

PURPOSE: To investigate the factors influencing and long-term effects of manual myotomy (MM) occurring during physiotherapy for congenital muscular torticollis (CMT). METHODS: We retrospectively collected the clinical data of children with CMT receiving physiotherapy between 2008 and 2018. The children were divided into manual myotomy (MM) and non-manual myotomy (NMM) groups according to whether MM occurred during treatment. We assessed physiotherapy outcomes in children with CMT using craniofacial asymmetry parameters and the Cheng-Tang rating score. By measuring the ear-eye distance, ear-nose distance, eye-mouth distance, ear-mouth distance, half-head circumference, and half-head top at two sides to evaluate craniofacial asymmetry. Based on the Cheng-Tang assessment criteria, we recorded the range of rotation, range of lateral flexion, the status of the contracted muscle, the hardness of the mass, the extent of head tilting during activities and sleeping, the status of daily activities, face size, type of head shape, cranial changes, and subjective head tilting to assess the effectiveness of treatment. Clinical data and outcome indicators (craniofacial asymmetry parameters and Cheng-Tang rating score) were compared. RESULTS: The MM group had a significantly higher total Cheng-Tang rating score than the NMM group (P < 0.05). Age at initial physiotherapy session was the risk factor for MM during physiotherapy. CONCLUSION: Children with CMT developing MM during physiotherapy generally have a good outcome, although we do not recommend MM as a goal of treatment. Physiotherapists should understand this phenomenon, assess relevant factors to predict risk, and carefully observe treatment to prevent possible complications.


Assuntos
Fibroma , Miotomia , Torcicolo , Criança , Humanos , Lactente , Músculos do Pescoço , Modalidades de Fisioterapia , Estudos Retrospectivos , Torcicolo/complicações , Torcicolo/congênito , Torcicolo/cirurgia , Resultado do Tratamento
17.
J Orthop Surg Res ; 17(1): 300, 2022 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-35658921

RESUMO

BACKGROUND: Fractures are the most common type of unintentional injury in children, with traumatic upper limb fractures accounting for approximately 80% of all childhood fractures. Many epidemiological investigations of upper limb fractures in children have been conducted, but with the development of society, the patterns of childhood fractures may have changed. This study aimed to analyze the epidemiology and economic cost factors of upper limb fractures in Chinese children. METHODS: We retrospectively reviewed children with upper limb fractures or old upper limb fractures hospitalized between December 1, 2015, and December 31, 2019, in 22 tertiary children's hospitals, under China's Futang Research Center of Pediatric Development. We used the ICD10 codes on the front sheet of their medical records to identify cases and extracted data on age, sex, injury cause, fracture site, treatment, the year of admission and discharge, visiting time, and various costs during hospitalization from the medical record. RESULTS: A total of 32,439 children (21,478 boys and 10,961 girls) were identified, of whom 32,080 had fresh fractures and 359 had old fractures. The peak age was 3-6 years in both sexes. A total of 4788 were infants, 14,320 were preschoolers, 10,499 were in of primary school age, and 2832 were adolescent. Fractures were most frequent in autumn (August to October). Admissions peaked at 0 o'clock. Among the 32,080 children with fresh upper limb fractures, the most common fracture site was the distal humerus, with a total of 20,090 fracture events including 13,134 humeral supracondylar fractures and 4914 lateral humeral condyle fractures. The most common cause of injuries was falling over. The most common joint dislocation accompanying upper limb fractures occurred in the elbow, involving 254 cases. Surgery was performed in 31,274 children, and 806 did not receive surgery. Among those with clear operative records, 10,962 children were treated with open reduction and 18,066 with closed reduction. The number of cases was largest in the East China region (Anhui Province, Shandong Province, Jiangsu Province, Zhejiang Province, and Fujian Province), with 12,065 cases overall. Among the 359 children with old fractures, 118 were admitted with a diagnosis of "old humerus fracture," accounting for the highest proportion; 244 underwent surgical open reduction, 16.16% of whom had osteotomy. For the children with fresh fractures, the average total hospital cost was 10,994 yuan, and the highest average total hospital cost was 14,053 yuan, for humeral shaft fractures. For the children with old fractures, the average total hospital cost was 15,151 yuan, and the highest average total hospital cost was 20,698 yuan, for old ulna fractures. Cost of materials was the principle factor affecting total hospital cost, followed by surgery and anesthesia costs, both in children with fresh fractures and those with old fractures. Significant differences were observed in all hospital costs (P < 0.001) except treatment costs (P = 0.702), between children with fresh fractures and those with old fractures. Among the 32,439 children, full self-payment accounted for the highest proportion of all payment methods, involving 17,088 cases, with an average cost of 11,111 yuan. CONCLUSION: Information on the epidemiological characteristics of childhood fractures suggests that health and safety education and protective measures should be strengthened to prevent upper limb fractures in children. For both fresh and old fractures, the cost of materials was the principal factor affecting total hospital cost, followed by surgery and anesthesia costs. The overall average total hospital cost is higher in children with old fractures than in children with fresh fractures. Among all children, full self-payment, at 53% of children, accounted for the highest proportion of all payment methods. Hospital costs are a headache for those families who will pay on their own. It can lead to a delayed treatment and unhealed fractures or malunion in some children. Therefore, the child trauma care system and training on fractures need to be improved, to reduce the late presentation of fractures. These combined measures will improve children's quality of life, reduce the expenditure of families, and decrease the public health burden. To provide better medical services for children, authorities must improve the allocation of health resources, establish a comprehensive medical security system for children, and set up more child trauma centers.


Assuntos
Criança Hospitalizada , Fraturas do Úmero , Adolescente , Criança , Pré-Escolar , Cotovelo , Feminino , Humanos , Fraturas do Úmero/cirurgia , Fraturas do Úmero/terapia , Lactente , Masculino , Qualidade de Vida , Estudos Retrospectivos , Centros de Atenção Terciária
18.
J Transl Med ; 20(1): 277, 2022 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-35729639

RESUMO

Glioma is the most common malignant tumors in the brain. Previous studies have revealed that, as the innate immune cells in nervous system, microglia cells were involved in glioma pathology. And, the resident microglia displayed its specific biological roles which distinguished with peripheral macrophages. In this study, an integrated analysis was performed based on public resource database to explore specific biological of microglia within glioma. Through comprehensive analysis, the biological characterization underlying two conditions, glioma microglia compared to glioma macrophage (MicT/MacT) as well as glioma microglia compared to normal microglia (MicT/MicN), were revealed. Notably, nine core MicT/MicN genes displayed closely associations with glioma recurrence and prognosis, such as P2RY2, which was analyzed in more than 2800 glioma samples from 25 studies. Furthermore, we applied a random walk based strategy to identify microglia specific subpathways and developed SubP28 signature for glioma prognostic analysis. Multiple validation data sets confirmed the predictive performance of SubP28 and involvement in molecular subtypes. The associations between SuP28 score and microglia M1/M2 polarization were also explored for both GBM and LGG types. Finally, a comprehensive drug-subpathway network was established for screening candidate medicable molecules (drugs) and identifying therapeutic subpathway targets. In conclusions, the comprehensive analysis of microglia related gene and functional signatures in glioma pathobiologic events by large-scale data sets displayed a framework to dissect inner connection between microglia and glioma, and identify robust signature for glioma clinical implications.


Assuntos
Neoplasias Encefálicas , Glioma , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Avaliação Pré-Clínica de Medicamentos , Glioma/genética , Glioma/patologia , Humanos , Macrófagos/patologia , Microglia/patologia , Prognóstico , Receptores Purinérgicos P2Y2
19.
Environ Int ; 163: 107237, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35429917

RESUMO

OBJECTIVE: We aimed to investigate whether urinary metal mixtures are associated with the homeostasis of inflammatory mediators in middle-aged and older adults. METHODS: A four-visit repeated-measures study was conducted with 98 middle-aged and older adults from five communities in Beijing, China. Only one person was lost to follow-up at the third visit. Ultimately, 391 observations were included in the analysis. The urinary concentrations of 10 metals were measured at each visit using inductively coupled plasma mass spectrometry (ICP-MS) with a limit of detection (LOD) ranging from 0.002 to 0.173 µg/L, and the detection rates were all above 84%. Similarly, 14 serum inflammatory mediators were measured using a Beckman Coulter analyzer and the Bio-Plex MAGPIX system. A linear mixed model (LMM), LMM with least absolute shrinkage and selection operator regularization (LMMLASSO), and Bayesian kernel machine regression (BKMR) were adopted to explore the effects of urinary metal mixtures on inflammatory mediators. RESULTS: In LMM, a two-fold increase in urinary cesium (Cs) and chromium (Cr) was statistically associated with -35.22% (95% confidence interval [CI]: -53.17, -10.40) changes in interleukin 6 (IL-6) and -11.13% (95 %CI: -20.67, -0.44) in IL-8. Urinary copper (Cu) and selenium (Se) was statistically associated with IL-6 (88.10%, 95%CI: 34.92, 162.24) and tumor necrosis factor-alpha (TNF-α) (22.32%, 95%CI: 3.28, 44.12), respectively. Similar results were observed for the LMMLASSO and BKMR. Furthermore, Cr, Cs, Cu, and Se were significantly associated with other inflammatory regulatory network mediators. For example, urinary Cs was statistically associated with endothelin-1, and Cr was statistically associated with endothelin-1 and intercellular adhesion molecule 1 (ICAM-1). Finally, the interaction effects of Cu with various metals on inflammatory mediators were observed. CONCLUSION: Our findings suggest that Cr, Cs, Cu, and Se may disrupt the homeostasis of inflammatory mediators, providing insight into the potential pathophysiological mechanisms of metal mixtures and chronic diseases.


Assuntos
Mediadores da Inflamação , Selênio , Idoso , Teorema de Bayes , Cromo , Endotelina-1 , Homeostase , Humanos , Interleucina-6 , Metais/toxicidade , Pessoa de Meia-Idade
20.
World J Microbiol Biotechnol ; 38(4): 73, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35288779

RESUMO

Chitosan (CS) is a kind of high molecular polymer with antibacterial properties. A copolymer with high bacteriostatic activity can be formed by grafting phenolic acid compounds into the chitosan molecular chain, which can inhibit the growth of dominant spoilage bacteria in aquatic products. The study aimed to investigate the antibacterial effect and mechanism of chitosan-grafted-phenolic acid copolymers on Shewanella putrefaciens (S. putrefaciens). CS-grafted-protocatechuic acid (CS-g-PA) and CS-grafted-gallic acid (CS-g-GA) were attained by EDC/NHS coupling reaction. The antibacterial tests indicated that CS-g-PA and CS-g-GA had the same minimum inhibitory concentration (MIC) (1.25 mg/mL) and minimum bactericidal concentration (MBC) (5.0 mg/mL) against S. putrefaciens. According to the change trend of growth curve, the growth of S. putrefaciens was significantly restrained under 2MIC graft copolymers (P < 0.05). Moreover, the increment of alkaline phosphatase (AKPase) activity and electrical conductivity demonstrated that the cell wall and membrane permeability of S. putrefaciens were damaged respectively. In addition, the increase of lactate dehydrogenase (LDHase) activity, protein and nucleic acid absorbance and the decrease of adenosine triphosphatase (ATPase) activity suggested that the cell membrane was incomplete and poor fluidity. The irregular shape of bacteria and the outflow of intercellular contents were also observed from scanning electron microscope (SEM). The above results manifested a great potential of CS-g-PA and CS-g-GA for use as food preservatives to aquatic products.


Assuntos
Quitosana , Shewanella putrefaciens , Membrana Celular , Quitosana/farmacologia , Hidroxibenzoatos , Permeabilidade , Polímeros/farmacologia
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