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OBJECTIVE: Traditional Chinese exercises (Taichi, Wuqinxi, Liuzijue, and Baduanjin) are considered effective alternative treatments for improving symptoms in the stable phase of COPD. However, the most effective exercise remains unknown. This study compared the effectiveness of different traditional Chinese exercises on pulmonary function in patients with stable chronic obstructive pulmonary disease (COPD) using a network meta-analysis. METHODS: From database establishment until September 2023, eligible randomized controlled trials (RCTs) were searched. Two reviewers performed the risk of bias assessment of the included studies using the Cochrane Collaboration tool, and the evidence level was suggested using the GRADE system. RESULTS: Fifty-seven studies comprising 4294 patients were included. The results of the network meta-analysis show that Baduanjin was most effective in improving the forced expiratory volume in the first second (FEV1). However, Liuzijue significantly improved the first-second forced vital capacity percentage of expected value (FEV1%) and the ratio of the forced expiratory volume in the first second to the forced vital capacity (FEV1/FVC). The probability ranking results indicated that Liuzijue was the most effective, followed by Baduanjin, Wuqinxi, and Taichi. Subgroup analysis in conjunction with intervention duration revealed that Liuzijue had a significant advantage over other interventions for improving FEV1, FEV1%, and FEV1/FVC within 6 months and improved FEV1% and FEV1/FVC for ≥ 6 months. Moreover, Subgroup analysis based on baseline pulmonary function revealed that Liuzijue had a significant advantage over other interventions for improving FEV1% within severe and moderate groups. Finally, Subgroup analysis based on the frequency of interventions showed that Liuzijue was still more effective in improving FEV1, FEV1%, and FEV1/FVC in the ≥ three times one week. CONCLUSION: Liuzijue was more effective than Taichi, Wuqinxi, Liuzijue, and Baduanjin in improving pulmonary function in patients with stable COPD.
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Metaanálisis en Red , Enfermedad Pulmonar Obstructiva Crónica , Enfermedad Pulmonar Obstructiva Crónica/terapia , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Humanos , Terapia por Ejercicio/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Medicina Tradicional China/métodos , Pruebas de Función Respiratoria , Volumen Espiratorio Forzado , Pueblos del Este de AsiaRESUMEN
Actinomycosis is a rare chronic granulomatous disease characterized by granuloma formation and tissue fibrosis with sinus tracts, often misdiagnosed due to its similarity to many infectious and non-infectious diseases. This report presents a case of a 60-year-old female with more than 10 years history of rheumatoid arthritis who developed actinomycosis infection after long-term treatment with immunosuppressants and biologics, including methotrexate, leflunomide, and infliximab, leading to recurrent joint pain, poorly controlled rheumatoid arthritis activity, and persistent elevation of white blood cell counts. Abdominal CT revealed a pelvic mass and right ureteral dilation. Pathological examination of cervical tissue showed significant neutrophil infiltration and sulfur granules, indicating actinomycosis. The patient received 18 months of doxycycline treatment for the infection and continued rheumatoid arthritis therapy with leflunomide, hydroxychloroquine sulfate, and tofacitinib, resulting in improved joint symptoms and normalized white blood cell counts. After 2 years of follow-up, the patient remained stable with no recurrence. This case highlights the importance of clinicians being vigilant for infections, particularly chronic, occult infections from rare pathogens, in rheumatoid arthritis patients on potent immunosuppressants and biologics, advocating for early screening and diagnosis.
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Actinomicosis , Artritis Reumatoide , Obstrucción Ureteral , Humanos , Femenino , Artritis Reumatoide/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Persona de Mediana Edad , Actinomicosis/diagnóstico , Actinomicosis/complicaciones , Actinomicosis/tratamiento farmacológico , Obstrucción Ureteral/etiología , Inmunosupresores/uso terapéuticoRESUMEN
Objective: To characterize BMI in Chinese patients with RA vs US patients and examine its association with joint damage in Chinese patients. Methods: Each of the 1318 patients from a real-world Chinese RA population was first stratified by gender and then individually age-matched with one American RA patient from the US National Health and Nutritional Examination Survey 1999-2018. Data on BMI, bilateral hand radiographs and risk factors at enrolment were collected but radiographs were unavailable for the American patients. Logistic regression was used to evaluate the association of BMI with radiographic joint damage (RJD) in Chinese patients. Results: Chinese patients had a significantly lower BMI [(weighted) median 21.8 vs 29.8 kg/m2; P < 0.001] and a higher prevalence of being underweight (15.2% vs 1.1%; P < 0.05) than their American counterparts. Underweight Chinese patients (BMI <18.5) had higher modified total Sharp scores (median 17 vs 10) and joint space narrowing (JSN) subscores (median 6 vs 2) (both P < 0.05) than normal-weight patients (BMI ≥18.5-<24). After controlling for confounding, continuous BMI was cross-sectionally negatively associated with RJD [adjusted prevalence odds ratio (OR) 0.90 (95% CI 0.85, 0.96)] and JSN [adjusted prevalence OR 0.92 (95% CI 0.87, 0.96)]; being underweight vs normal weight was associated with RJD [adjusted prevalence OR 2.14 (95% CI 1.37, 3.35)] and JSN [adjusted prevalence OR 1.77 (95% CI 1.10, 2.84)]. Conclusion: Low BMI and being underweight were cross-sectionally associated with joint damage in Chinese RA patients, especially JSN, suggesting the clinical importance of identifying underweight patients and focusing on weight gain to prevent joint damage.
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Cerebral venous sinus thrombosis (CVST) and hyperlipidemia are severe complications of L-Asparaginase (L-Asp) during the treatment of B-cell acute lymphoblastic leukemia (B-ALL). Herein, we reported a 9-year-old B-ALL boy who underwent abnormal hypertriglyceridemia and CVST presenting as seizures and disturbance of consciousness twice during the induction therapy. Fortunately, he survived treatment with anticoagulant and lipid-lowering therapy. No thrombophilia-related gene mutation was detected, but a heterozygous mutation in lipoprotein lipase (LPL) gene was identified. His neurological symptoms were managed with short-term anticoagulant therapy and long-term lipid-lowering therapy. This case illustrated the manifestation and potential pathogenesis of CVST and highlighted the essentiality of screening baseline lipid profile and dyslipidemia- and thrombophilia-related gene mutation.
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Perfluorooctane sulfonamide (PFOSA) is an immediate perfluorooctanesulfonate (PFOS) precursor (PreFOS). Previous studies have shown PFOSA to induce stronger toxic responses compared to other perfluorinated compounds (PFCs). However, the specific nature of PFOSA-induced toxicity, whether autonomous or mediated by its metabolite PFOS, has not been fully elucidated. This study systematically investigates the immunomodulatory effects of PFOSA and PFOS in zebrafish (Danio rerio). Exposure to PFOSA compromised the zebrafish's ability to defend against pathogenic infections, as evidenced by increased bacterial adhesion to their skin and reduced levels of the biocidal protein lysozyme (LYSO). Moreover, PFOSA exposure was associated with disruptions in inflammatory markers and immune indicators, along with a decrease in immune cell counts. The findings from this study suggest that the immunotoxicity effects of PFOSA are primarily due to its own toxicity rather than its metabolite PFOS. This conclusion was supported by dose-dependent responses, the severity of observed effects, and multivariate analysis. In addition, our experiments using NF-κB-morpholino knock-down techniques further confirmed the role of the Nuclear factor-κappa B pathway in mediating PFOSA-induced immunotoxicity. In conclusion, this study reveals that PFOSA impairs the immune system in zebrafish through an autotoxic mechanism, providing valuable insights for assessing the ecological risks of PFOSA.
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Relapse and treatment resistance pose significant challenges in the management of pediatric B cell acute lymphoblastic leukemia (B-ALL) and acute myeloid leukemia (AML). The efficacy of immunotherapy in leukemia remains limited due to factors such as the immunosuppressive tumor microenvironment (TME) and lack of suitable immunotherapeutic targets. Thus, an in-depth characterization of the TME in pediatric leukemia is warranted to improve the efficacy of immunotherapy. Here, we used single-cell RNA sequencing (scRNA-seq) to characterize the TME of pediatric B-ALL and AML, focusing specifically on bone-marrow-derived T cells. Moreover, we investigated the transcriptome changes during the initiation, remission, and relapse stages of pediatric AML. Our findings revealed that specific functional expression programs correlated with fluctuations in various T cell subsets, which may be associated with AML progression and relapse. Furthermore, our analysis of cellular communication networks led to the identification of VISTA, CD244, and TIM3 as potential immunotherapeutic targets in pediatric AML. Finally, we detected elevated proportions of γδ T cells and associated functional genes in samples from pediatric patients diagnosed with B-ALL and AML, which could inform the development of novel therapeutic approaches, potentially focusing on γδ T cells.
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Leucemia Mieloide Aguda , Análisis de la Célula Individual , Microambiente Tumoral , Humanos , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Análisis de la Célula Individual/métodos , Niño , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/inmunología , Leucemia Mieloide Aguda/patología , Transcriptoma , Receptor 2 Celular del Virus de la Hepatitis A/genética , Receptor 2 Celular del Virus de la Hepatitis A/metabolismo , Perfilación de la Expresión Génica/métodos , Preescolar , Masculino , Femenino , Antígenos B7/genética , Adolescente , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patología , Regulación Leucémica de la Expresión GénicaRESUMEN
Carbon source is a key factor determining the denitrifying effectiveness and efficiency in wastewater treatment plants (WWTPs). Whereas, the relationships between diverse and distinct denitrifying communities and their favorable carbon sources in full-scale WWTPs were not well-understood. This study performed a systematic analysis of the relationships between the denitrifying community and carbon sources by using 15 organic compounds from four categories and activated sludge from 8 full-scale WWTPs. Results showed that, diverse denitrifying bacteria were detected with distinct relative abundances in 8 WWTPs, such as Haliangium (1.98-4.08%), Dechloromonas (2.00-3.01%), Thauera (0.16-1.06%), Zoogloea (0.09-0.43%), and Rhodoferax (0.002-0.104%). Overall, acetate resulted in the highest denitrifying activities (1.21-4.62 mg/L/h/gMLSS), followed by other organic acids (propionate, butyrate and lactate, etc.). Detectable dissimilatory nitrate reduction to ammonium (DNRA) was observed for all 15 carbon sources. Methanol and glycerol resulted in the highest DRNA. Acetate, butyrate, and lactate resulted in the lowest DNRA. Redundancy analysis and 16S cDNA amplicon sequencing suggested that carbon sources within the same category tended to correlate to similar denitrifiers. Methanol and ethanol were primarily correlated to Haliangium. Glycerol and amino acids (glutamate and aspartate) were correlated to Inhella and Sphaerotilus. Acetate, propionate, and butyrate were positively correlated to a wide range of denitrifiers, explaining the high efficiency of these carbon sources. Additionally, even within the same genus, different amplicon sequence variants (ASVs) performed distinctly in terms of carbon source preference and denitrifying capabilities. These findings are expected to benefit carbon source formulation and selection in WWTPs.
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Carbono , Desnitrificación , Eliminación de Residuos Líquidos , Aguas Residuales , Aguas Residuales/química , Aguas Residuales/microbiología , Carbono/metabolismo , Eliminación de Residuos Líquidos/métodos , Bacterias/metabolismo , Bacterias/clasificación , Bacterias/genética , Aguas del Alcantarillado/microbiología , Nitratos/metabolismo , Nitratos/análisis , Compuestos de Amonio/metabolismoRESUMEN
Acid sphingomyelinase (ASM) has been reported to increase tissue ceramide and thereby mediate hyperhomocysteinemia (hHcy)-induced glomerular nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome activation, inflammation, and sclerosis. In the present study, we tested whether somatic podocyte-specific silencing of Smpd1 gene (mouse ASM gene code) attenuates hHcy-induced NLRP3 inflammasome activation and associated extracellular vesicle (EV) release in podocytes and thereby suppresses glomerular inflammatory response and injury. In vivo, somatic podocyte-specific Smpd1 gene silencing almost blocked hHcy-induced glomerular NLRP3 inflammasome activation in Podocre (podocyte-specific expression of cre recombinase) mice compared with control littermates. By nanoparticle tracking analysis (NTA), floxed Smpd1 shRNA transfection was found to abrogate hHcy-induced elevation of urinary EV excretion in Podocre mice. In addition, Smpd1 gene silencing in podocytes prevented hHcy-induced immune cell infiltration into glomeruli, proteinuria, and glomerular sclerosis in Podocre mice. Such protective effects of podocyte-specific Smpd1 gene silencing were mimicked by global knockout of Smpd1 gene in Smpd1-/- mice. On the contrary, podocyte-specific Smpd1 gene overexpression exaggerated hHcy-induced glomerular pathological changes in Smpd1trg/Podocre (podocyte-specific Smpd1 gene overexpression) mice, which were significantly attenuated by transfection of floxed Smpd1 shRNA. In cell studies, we also confirmed that Smpd1 gene knockout or silencing prevented homocysteine (Hcy)-induced elevation of EV release in the primary cultures of podocyte isolated from Smpd1-/- mice or podocytes of Podocre mice transfected with floxed Smpd1 shRNA compared with WT/WT podocytes. Smpd1 gene overexpression amplified Hcy-induced EV secretion from podocytes of Smpd1trg/Podocre mice, which was remarkably attenuated by transfection of floxed Smpd1 shRNA. Mechanistically, Hcy-induced elevation of EV release from podocytes was blocked by ASM inhibitor (amitriptyline, AMI), but not by NLRP3 inflammasome inhibitors (MCC950 and glycyrrhizin, GLY). Super-resolution microscopy also showed that ASM inhibitor, but not NLRP3 inflammasome inhibitors, prevented the inhibition of lysosome-multivesicular body interaction by Hcy in podocytes. Moreover, we found that podocyte-derived inflammatory EVs (released from podocytes treated with Hcy) induced podocyte injury, which was exaggerated by T cell coculture. Interstitial infusion of inflammatory EVs into renal cortex induced glomerular injury and immune cell infiltration. In conclusion, our findings suggest that ASM in podocytes plays a crucial role in the control of NLRP3 inflammasome activation and inflammatory EV release during hHcy and that the development of podocyte-specific ASM inhibition or Smpd1 gene silencing may be a novel therapeutic strategy for treatment of hHcy-induced glomerular disease with minimized side effect.NEW & NOTEWORTHY In the present study, we tested whether podocyte-specific silencing of Smpd1 gene attenuates hyperhomocysteinemia (hHcy)-induced nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome activation and associated inflammatory extracellular vesicle (EV) release in podocytes and thereby suppresses glomerular inflammatory response and injury. Our findings suggest that acid sphingomyelinase (ASM) in podocytes plays a crucial role in the control of NLRP3 inflammasome activation and inflammatory EV release during hHcy. Based on our findings, it is anticipated that the development of podocyte-specific ASM inhibition or Smpd1 gene silencing may be a novel therapeutic strategy for treatment of hHcy-induced glomerular disease with minimized side effects.
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Hiperhomocisteinemia , Inflamasomas , Ratones Noqueados , Proteína con Dominio Pirina 3 de la Familia NLR , Podocitos , Esfingomielina Fosfodiesterasa , Animales , Esfingomielina Fosfodiesterasa/genética , Esfingomielina Fosfodiesterasa/metabolismo , Podocitos/metabolismo , Podocitos/patología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Hiperhomocisteinemia/metabolismo , Hiperhomocisteinemia/complicaciones , Hiperhomocisteinemia/genética , Inflamasomas/metabolismo , Inflamasomas/genética , Glomérulos Renales/patología , Glomérulos Renales/metabolismo , Glomerulonefritis/patología , Glomerulonefritis/metabolismo , Glomerulonefritis/genética , Silenciador del Gen , Ratones , Ratones Endogámicos C57BL , Vesículas Extracelulares/metabolismo , Masculino , Modelos Animales de EnfermedadRESUMEN
Juvenile myelomonocytic leukemia (JMML) is a disorder characterized by the simultaneous presence of myeloproliferative and myelodysplastic features, primarily affecting infants and young children. Due to the heterogeneous genetic background among patients, the current clinical and laboratory prognostic features are insufficient for accurately predicting outcomes. Thus, there is a pressing need to identify novel prognostic indicators. Red cell distribution width (RDW) is a critical parameter reflecting the variability in erythrocyte size. Recent studies have emphasized that elevated RDW serves as a valuable predictive marker for unfavorable outcomes across various diseases. However, the prognostic role of RDW in JMML remains unclear. Patients with JMML from our single-center cohort between January 2008 and December 2019 were included. Overall, 77 patients were eligible. Multivariate Cox proportional hazard models showed that patients with red cell distribution width coefficient of variation (RDW-CV) >17.35% at diagnosis were susceptible to much worse overall survival rate (hazard ratio [HR] = 5.22, confidence interval [CI] = 1.50-18.21, P = .010). Besides, the combination of RDW elevation and protein phosphatase non-receptor type 11 (PTPN11) mutation was likely to predict a subgroup with the worst outcomes in our cohort. RDW is an independent prognostic variable in JMML subjects. RDW may be regarded as an inexpensive biomarker to predict the clinical outcome in patients with JMML.
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Atherosclerosis is an inflammatory disease of blood vessels involving the immune system. Natural killer T (NKT) cells, as crucial components of the innate and acquired immune systems, play critical roles in the development of atherosclerosis. However, the mechanism and clinical relevance of NKT cells in early atherosclerosis are largely unclear. The study investigated the mechanism influencing NKT cell function in apoE deficiency-induced early atherosclerosis. Our findings demonstrated that there were higher populations of NKT cells and interferon-gamma (IFN-γ)-producing NKT cells in the peripheral blood of patients with hyperlipidemia and in the aorta, blood, spleen, and bone marrow of early atherosclerotic mice compared with the control groups. Moreover, we discovered that the infiltration of CD80+ macrophages and CD1d expression on CD80+ macrophages in atherosclerotic mice climbed remarkably. CD1d expression increased in CD80+ macrophages stimulated by oxidized low-density lipoprotein (ox-LDL) ex vivo and in vitro. Ex vivo coculture of macrophages with NKT cells revealed that ox-LDL-induced CD80+ macrophages presented lipid antigen α-Galcer (alpha-galactosylceramide) to NKT cells via CD1d, enabling NKT cells to express more IFN-γ. Furthermore, a greater proportion of CD1d+ monocytes and CD1d+CD80+ monocytes were found in peripheral blood of hyperlipidemic patients compared with that of healthy donors. Positive correlations were found between CD1d+CD80+ monocytes and NKT cells or IFN-γ+ NKT cells in hyperlipidemic patients. Our findings illustrated that CD80+ macrophages stimulated NKT cells to secrete IFN-γ via CD1d-presenting α-Galcer, which may accelerate the progression of early atherosclerosis. Inhibiting lipid antigen presentation by CD80+ macrophages to NKT cells may be a promising immune target for the treatment of early atherosclerosis.NEW & NOTEWORTHY This work proposed the ox-LDL-CD80+ monocyte/macrophage-CD1d-NKT cell-IFN-γ axis in the progression of atherosclerosis. The proinflammatory IFN-γ+ NKT cells are closely related to CD1d+CD80+ monocytes in hyperlipidemic patients. Inhibiting CD80+ macrophages to present lipid antigens to NKT cells through CD1d blocking may be a new therapeutic target for atherosclerosis.
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Antígenos CD1d , Aterosclerosis , Antígeno B7-1 , Hiperlipidemias , Lipoproteínas LDL , Macrófagos , Células T Asesinas Naturales , Animales , Humanos , Células T Asesinas Naturales/inmunología , Células T Asesinas Naturales/metabolismo , Antígenos CD1d/metabolismo , Antígenos CD1d/inmunología , Antígenos CD1d/genética , Aterosclerosis/inmunología , Aterosclerosis/metabolismo , Aterosclerosis/patología , Hiperlipidemias/inmunología , Hiperlipidemias/metabolismo , Lipoproteínas LDL/inmunología , Lipoproteínas LDL/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo , Masculino , Ratones , Antígeno B7-1/metabolismo , Antígeno B7-1/inmunología , Interferón gamma/metabolismo , Interferón gamma/inmunología , Ratones Endogámicos C57BL , Femenino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To explore the association of geriatric nutrition risk index (GNRI), a traditional albumin-body weight calculation, with myopenia in patients with rheumatoid arthritis (RA) and compare its ability to identify myopenia with protein indicators. METHODS: This cross-sectional study was carried out based on a Chinese RA cohort. Clinical data and protein indicators (including albumin, globulin, albumin to globulin ratio, prealbumin, hemoglobin) were collected. GNRI was estimated by serum albumin and body weight. Myopenia was indicated as muscle mass loss measured by bioelectric impedance analysis. RESULTS: There were 789 RA patients included with mean age 52.6 ± 12.6 years and 77.6% female. There were 41.3%, 18.0%, 27.5%, 13.2% patients with no (GNRI > 98), low (GNRI 92 to ≤ 98), moderate (GNRI 82 to < 92), and major nutrition-related risk (GNRI < 82). There were 406 (51.5%) RA patients with myopenia, RA patients with major nutrition-related risk had the highest prevalence of myopenia (87.5% vs. 73.3% vs. 50.0% vs. 26.1%). Multivariate logistic analysis showed that compared with no risk, RA patients with low (OR = 3.23, 95% CI: 1.86-5.61), moderate (OR = 9.56, 95% CI: 5.70-16.01), and major nutrition-related risk (OR = 28.91, 95% CI: 13.54-61.71) were associated with higher prevalence of myopenia. Receiver operating characteristic curves showed that GNRI (AUC = 0.79) performed a better identifiable ability toward myopenia than serum albumin (AUC = 0.66) or others indicators (AUC range 0.59 to 0.65), respectively. CONCLUSION: GNRI, an objective and convenient albumin-weight index, may be preferable for identifying myopenia in RA patients. Key Points ⢠We firstly elucidated the association of GNRI with muscle mass loss among RA patients, and compared its ability to identify muscle mass loss with serum albumin or other protein indicators. ⢠Major nutrition-related risk identified by GNRI showed the highest risk of muscle mass loss, GNRI demonstrated a greater ability to identify myopenia in RA patients. which indicated GNRI was an objective and convenient albumin-weight index to identify myopenia in RA patients.
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Artritis Reumatoide , Globulinas , Humanos , Femenino , Anciano , Adulto , Persona de Mediana Edad , Masculino , Evaluación Nutricional , Estudios Transversales , Estado Nutricional , Artritis Reumatoide/complicaciones , Atrofia Muscular , Albúmina Sérica , Peso Corporal , Músculos , Factores de RiesgoRESUMEN
BACKGROUND: Remnant cholesterol (RC) promotes cardiovascular disease (CVD) in the general population, but its role among rheumatoid arthritis (RA) patients remains unknown. We aimed to investigate circulating RC levels associated with incident CVD among Chinese patients with RA. METHODS: A total of 1018 RA patients free of baseline CVD were included and followed up in a prospective RA CVD cohort from 2001 to 2022. Fasting serum levels of triglycerides, total cholesterol (TC), low-density (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured, while RC and Non-HDL-C levels were calculated. The primary exposure was RC levels. A LASSO Cox model was used to select covariates. The Fine-Gray competing risk model was used to estimate hazard ratios (HRs). RESULTS: RA patients had a mean age of 53.9 years, and 802 (78.8%) were females. After a median follow-up of 5.54 years, 131 patients developed CVD with an incidence rate of 21.6 per 1000 person-years. Continuous and quartile-categorized RC levels were associated with incident CVD before and after multivariate adjustment and Bonferroni correction (all P < 0.001). There were no robust associations of other lipids with incident CVD. The fully adjusted HRs for RC were 2.30 (95% CI 1.58-3.35) per 1 mmol/L increase, and 2.40 (1.36-4.25) and 2.81 (1.60-4.94) for patients in the 3rd and 4th versus the 1st quartile, respectively. CONCLUSIONS: Circulating RC levels are positively associated with incident CVD among Chinese RA patients independent of known risk factors, implying its clinically preferable use for improving the stratification of CVD risk in RA patients.
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Artritis Reumatoide , Enfermedades Cardiovasculares , Colesterol , Lipoproteínas , Triglicéridos , Humanos , Artritis Reumatoide/sangre , Artritis Reumatoide/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/diagnóstico , Incidencia , Estudios Prospectivos , Colesterol/sangre , Estudios de Seguimiento , Adulto , China/epidemiología , Anciano , Biomarcadores/sangre , Estudios de Cohortes , Factores de RiesgoRESUMEN
TGF-ß/Smad signaling pathway plays an important role in the pathogenesis and progression of liver fibrosis. Silent information regulator 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+) dependent enzyme and responsible for deacetylating the proteins. Increasing numbers of reports have shown that the molecular mechanism of SIRT1 as an effective therapeutic target for liver fibrosis but the transformation is not very clear. In the present study, liver fibrotic tissues were screened by staining with Masson, hematoxylin-eosin staining (H&E) and Immunohistochemistry (IHC) for histopathological observation from the liver biopsy of seventy-seven rhesus monkey, which fixed with 4% paraformaldehyde (PFA) after treatment with high-fat diet (HFD) for two years. And the liver function was further determined by serum biochemical tests. The mRNA levels and protein expression of rat hepatic stellate (HSC-T6) cells were determined after treatment with Resveratrol (RSV) and Nicotinamide (NAM), respectively. The results showed that with the increasing of hepatic fibrosis in rhesus monkeys, the liver function impaired, and the transforming growth factor-ß1 (TGF-ß1), p-Smad3 (p-Smad3) and alpha-smooth muscle actin (α-SMA) was up-regulated, while SIRT1 and Smad7 were down-regulated. Moreover, when stimulated the HSC-T6 with RSV to activate SIRT1 for 6, 12, and 24 h, the results showed that RSV promoted the expression of smad7, while the expression of TGF-ß1, p-Smad3 and α-SMA were inhibited. In contrast, when the cells stimulated with NAM to inhibit SIRT1 for 6, 12, and 24 h, the Smad7 expression was decreased, while TGF-ß1, p-Smad3, and α-SMA expressions were increased. These results indicate that SIRT1 acts as an important protective factor for liver fibrosis, which may be attributed to inhibiting the signaling pathway of TGF-ß/Smad in hepatic fibrosis of the rhesus monkey.
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Cirrosis Hepática , Macaca mulatta , Transducción de Señal , Sirtuina 1 , Animales , Masculino , Ratas , Actinas/metabolismo , Línea Celular , Dieta Alta en Grasa/efectos adversos , Células Estrelladas Hepáticas/metabolismo , Células Estrelladas Hepáticas/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Hígado/efectos de los fármacos , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patología , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/tratamiento farmacológico , Niacinamida/farmacología , Resveratrol/farmacología , Transducción de Señal/efectos de los fármacos , Sirtuina 1/metabolismo , Proteínas Smad/metabolismo , Proteína smad3/metabolismo , Proteína smad7/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
The exceptional performance of graphene has driven the advancement of its preparation techniques and applications. Laser-induced graphene (LIG), as a novel graphene preparation technique, has been applied in various fields. Graphene periodic structures created by the LIG technique exhibit superhydrophobic characteristics and can be used for deicing and anti-icing applications, which are significantly influenced by the laser parameters. The laser surface treatment process was simulated by a finite element software analysis (COMSOL Multiphysics) to optimize the scanning parameter range, and the linear array surface structure was subsequently fabricated by the LIG technique. The generation of graphene was confirmed by Raman spectroscopy and energy-dispersive X-ray spectroscopy. The periodic linear array structure was observed by scanning electron microscopy (SEM) and confocal laser imaging (CLSM). In addition, CLSM testings, contact angle measurements, and delayed icing experiments were systematically performed to investigate the effect of scanning speed on surface hydrophobicity. The results show that high-quality and uniform graphene can be achieved using the laser scanning speed of 125 mm/s. The periodic linear array structures can obviously increase the contact angle and suppress delayed icing. Furthermore, these structures have the enhanced ability of the electric heating deicing, which can reach 100 °C and 240 °C within 15 s and within 60 s under the DC voltage power supply ranging from 3 to 7 V, respectively. These results indicate that the LIG technique can be developed to provide an efficient, economical, and convenient approach for preparing graphene and that the hydrophobic surface array structure based on LIG has considerable potential for deicing and anti-icing applications.
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There has been a significant shift in research focus in recent years toward laser-induced graphene (LIG), which is a high-performance material with immense potential for use in energy storage, ultrahydrophobic water applications, and electronic devices. In particular, LIG has demonstrated considerable potential in the field of high-precision human motion posture capture using flexible sensing materials. In this study, we investigated the surface morphology evolution and performance of LIG formed by varying the laser energy accumulation times. Further, to capture human motion posture, we evaluated the performance of highly accurate flexible wearable sensors based on LIG. The experimental results showed that the sensors prepared using LIG exhibited exceptional flexibility and mechanical performance when the laser energy accumulation was optimized three times. They exhibited remarkable attributes, such as high sensitivity (~41.4), a low detection limit (0.05%), a rapid time response (response time of ~150 ms; relaxation time of ~100 ms), and excellent response stability even after 2000 s at a strain of 1.0% or 8.0%. These findings unequivocally show that flexible wearable sensors based on LIG have significant potential for capturing human motion posture, wrist pulse rates, and eye blinking patterns. Moreover, the sensors can capture various physiological signals for pilots to provide real-time capturing.
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Grafito , Dispositivos Electrónicos Vestibles , Humanos , Captura de Movimiento , Electrónica , Rayos LáserRESUMEN
OBJECTIVE: Most reported research has primarily investigated wild-type transthyretin cardiac amyloidosis (ATTRwt-CA). However, the application of bone scintigraphy for hereditary transthyretin cardiac amyloidosis (ATTRv-CA) has not been systematically investigated. Therefore, in this study, we aimed to evaluate the diagnostic value of 99mTc-PYP scintigraphy in ATTRv-CA. METHODS: Fifty-four patients were enrolled in a highly suspected cardiac amyloidosis cohort. Transthyretin (TTR) gene characteristics were summarized in the ATTRv-CA group. In 99mTc-PYP scintigraphy, the diagnostic efficiency of the visual score (VGS) and heart-to-contralateral chest (H/CL) ratio were evaluated. Furthermore, the interobserver consistency among the diagnosticians was investigated. RESULTS: Twenty-eight patients were diagnosed with ATTRv-CA with eight genotypes. The Ala97Ser genotype accounts for 46% (n = 13) with a mean age of disease onset, definite diagnosis, and interval of 61.6 ± 1.9, 66.5 ± 1.3, and 4.0 (3.0, 6.2) years, respectively. Their VGS is Grade 3, and their H/CL ratio is higher than that of the non-Ala97Ser group, but no statistical significance exists (mean H/CL: 1.95 ± 0.06 vs. 1.87 ± 0.02, p = 0.844). Additionally, ATTRv-CA patients showed VGS ≥ 2, and mean H/CL ratio of 2.09 ± 0.06. The sensitivity and specificity of VGS were 100% and 65%, respectively. And the interobserver consistency analysis of VGS showed the intraclass correlation coefficient is 0.522. The best cutoff value of H/CL ratio was 1.51 (AUC = 0.996), and the diagnostic consistency of H/CL (bias: 0.018) was high. CONCLUSIONS: Ala97Ser is the most common genotype in ATTRv-CA in our cohort, with characteristics of later onset and rapid progression, but delayed diagnosis and extensive 99mTc-PYP uptake. Overall, ATTRv-CA patients showed moderate-to-extensive myocardial 99mTc-PYP uptake. Additionally, VGS carries subjectivity, low specialty and interobserver consistency. But H/CL exhibit high diagnostic efficacy and interobserver consistency. The H/CL ratio is more useful than VGS.
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Neuropatías Amiloides Familiares , Cardiomiopatías , Humanos , Pirofosfato de Tecnecio Tc 99m , Prealbúmina/genética , Corazón , Neuropatías Amiloides Familiares/diagnóstico por imagen , Neuropatías Amiloides Familiares/genética , Cintigrafía , Cardiomiopatías/diagnóstico por imagenRESUMEN
BACKGROUND: For the unclear pathogenesis of Sjogren's syndrome (SS), further exploration is necessary. Mesenchymal stem cells (MSCs) and derived exosomes (MSCs-exo) have exhibited promising results in treating SS. OBJECT: This study aimed to investigate the effect and mechanism of human umbilical cord MSCs (UC-MSCs) on SS. METHODS: Nonobese Diabetic (NOD) mouse splenic T cells were co-cultured with UC-MSCs and UC-MSCs-exo, and interferon-gamma (IFN-γ), interleukin (IL)-6, IL-10, prostaglandin E2 (PGE2), and transforming growth factor-ß1 (TGF-ß1) levels in the supernatant were assessed by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Co-cultured T cells were injected into NOD mice via the tail vein. The inflammatory cell infiltration in the intestine and the submandibular gland was characterized by hematoxylin-eosin staining. Treg/Th17 homeostasis within the spleen was determined by flow cytometry. Gut microbiota was detected by 16S rRNA sequencing, and the relationship between differential microbiota and Treg/Th17 cytokines was analyzed by the Pearson correlation coefficient. RESULTS: UC-MSCs, UC-MSCs-exo, and NOD mouse splenic T cells were successfully cultured and identified. After T cells were co-cultured with UC-MSCs and UC-MSCs-exo, both IFN-γ and IL-6 were decreased while IL-10, PGE2, and TGF-ß1 were increased in transcriptional and translational levels. UC-MSCs and UC-MSCs-exo partially restored salivary secretion function, reduced Ro/SSA antibody and α-Fodrin immunoglobulin A levels, reduced inflammatory cell infiltration in the intestine and submandibular gland, raised proportion of Treg cells, decreased IFN-γ, IL-6, IL-2, IL-17, lipopolysaccharide, and tumor necrosis factor-alpha levels, and raised IL-10, Foxp3, and TGF-ß1 levels by affecting co-cultured T cells. The intervention of UC-MSCs and UC-MSCs-exo improved intestinal homeostasis in NOD mice by increasing microbiota diversity and richness. Additionally, differential microbiota was significantly associated with Treg/Th17 cytokine levels. CONCLUSION: Human UC-MSCs and UC-MSCs-exo improved disease characterization of SS in NOD mice through regulation of gut microbiota and Treg/Th17 cellular immunity.
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Microbioma Gastrointestinal , Células Madre Mesenquimatosas , Síndrome de Sjögren , Animales , Ratones , Humanos , Linfocitos T Reguladores , Ratones Endogámicos NOD , Interleucina-10 , Interleucina-6 , Dinoprostona , ARN Ribosómico 16S , Síndrome de Sjögren/terapia , Factor de Crecimiento Transformador beta1 , Citocinas , Inmunidad Celular , Cordón UmbilicalRESUMEN
PURPOSE: Patient-tailored minimal residual disease (MRD) monitoring based on circulating tumor DNA (ctDNA) sequencing of leukemia-specific mutations enables early detection of relapse for pre-emptive treatment, but its utilization in pediatric acute myelogenous leukemia (AML) is scarce. Thus, we aim to examine the role of ctDNA as a prognostic biomarker in monitoring response to the treatment of pediatric AML. EXPERIMENTAL DESIGN: A prospective longitudinal study with 50 children with AML was launched, and sequential bone marrow (BM) and matched plasma samples were collected. The concordance of mutations by next-generation sequencing-based BM-DNA and ctDNA was evaluated. In addition, progression-free survival (PFS) and overall survival (OS) were estimated. RESULTS: In 195 sample pairs from 50 patients, the concordance of leukemia-specific mutations between ctDNA and BM-DNA was 92.8%. Patients with undetectable ctDNA were linked to improved OS and PFS versus detectable ctDNA in the last sampling (both P < 0.001). Patients who cleared their ctDNA post three cycles of treatment had similar PFS compared with persistently negative ctDNA (P = 0.728). In addition, patients with >3 log reduction but without clearance in ctDNA were associated with an improved PFS as were patients with ctDNA clearance (P = 0.564). CONCLUSIONS: Thus, ctDNA-based MRD monitoring appears to be a promising option to complement the overall assessment of pediatric patients with AML, wherein patients with continuous ctDNA negativity have the option for treatment de-escalation in subsequent therapy. Importantly, patients with >3 log reduction but without clearance in ctDNA may not require an aggressive treatment plan due to improved survival, but this needs further study to delineate.
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ADN Tumoral Circulante , Leucemia Mieloide Aguda , Humanos , Niño , ADN Tumoral Circulante/genética , Neoplasia Residual/genética , Neoplasia Residual/diagnóstico , Estudios Prospectivos , Estudios Longitudinales , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Medición de Riesgo , Biomarcadores de Tumor/genéticaRESUMEN
ABSTRACT: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer with resistant clonal propagation in recurrence. We performed high-throughput droplet-based 5' single-cell RNA with paired T-cell receptor (TCR) sequencing of paired diagnosis-relapse (Dx_Rel) T-ALL samples to dissect the clonal diversities. Two leukemic evolutionary patterns, "clonal shift" and "clonal drift" were unveiled. Targeted single-cell DNA sequencing of paired Dx_Rel T-ALL samples further corroborated the existence of the 2 contrasting clonal evolution patterns, revealing that dynamic transcriptional variation might cause the mutationally static clones to evolve chemotherapy resistance. Analysis of commonly enriched drifted gene signatures showed expression of the RNA-binding protein MSI2 was significantly upregulated in the persistent TCR clonotypes at relapse. Integrated in vitro and in vivo functional studies suggested that MSI2 contributed to the proliferation of T-ALL and promoted chemotherapy resistance through the posttranscriptional regulation of MYC, pinpointing MSI2 as an informative biomarker and novel therapeutic target in T-ALL.