RESUMO
Malignant insulinoma is an extremely rare type of functioning pancreatic neuroendocrine tumour with a high degree of malignancy and a high incidence of metastasis. However, it is still unclear how malignant insulinomas develop and metastasize. Serum amyloid P component (SAP), a member of the pentraxin protein family, is an acute-phase protein secreted by liver cells. The role of SAP in insulinoma and the related mechanism are still unknown. To determine the effect of SAP on insulinoma, we crossed Rip1-Tag2 mice, which spontaneously develop insulinoma, and SAP knockout (KO) mice to generate Rip1-Tag2;SAP-/- mice. We found that SAP deletion significantly promoted the growth, invasion and metastasis of malignant insulinoma through C-X-C motif chemokine ligand 12 (CXCL12) secreted by cancer-associated fibroblasts (CAFs). Further study showed that SAP deletion promoted CXCL12 secretion by CAFs through the CXCR4/p38/ERK signalling pathway. These findings reveal a novel role and mechanism of SAP in malignant insulinoma and provide direct evidence that SAP may be a therapeutic agent for this disease.
Assuntos
Quimiocina CXCL12 , Insulinoma , Sistema de Sinalização das MAP Quinases , Camundongos Knockout , Receptores CXCR4 , Animais , Humanos , Camundongos , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Linhagem Celular Tumoral , Proliferação de Células , Quimiocina CXCL12/metabolismo , Quimiocina CXCL12/genética , Progressão da Doença , Deleção de Genes , Insulinoma/genética , Insulinoma/patologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/genética , Receptores CXCR4/metabolismo , Receptores CXCR4/genéticaRESUMO
Depression is a relevant mental illness affecting hundreds of millions of people worldwide. As urbanization accelerates, agglomeration of populations has altered individual social network distances and life crowding, which in turn affects depressive prevalence. However, the association between depression and population agglomeration (PA) remains controversial. This study aims to explore whether and how PA could influence individual depression. Based on the China Health and Retirement Longitudinal Study (CHARLS) 2018, the empirical results showed that there was a U-shaped association between PA and individual CES-D scores. As PA increases, the risk of depression first decreases and then increases. CES-D was lowest at moderate aggregation. Dialect diversity (DD) was positively related to the incidence of individual depression. The higher the DD, the higher the risk of depression. Meanwhile, DD also played a moderating role in the association between PA and individual depression. Our observations suggest that the optimistic level of agglomeration for individual mental health is within 1500 to 2000 persons per square kilometer.
Assuntos
Depressão , Humanos , Depressão/epidemiologia , Masculino , Feminino , China/epidemiologia , Estudos Longitudinais , Pessoa de Meia-Idade , Idoso , Urbanização , Saúde Mental , Diversidade Cultural , PrevalênciaRESUMO
The purpose of this study is to evaluate the efficacy and safety of belimumab combined with the standard regimen in treating children with active lupus nephritis. This single-center, retrospective cohort study used clinical data of children with newly active lupus nephritis hospitalized in the Department of Nephrology between December 2004 and February 2023. Patients were divided into a belimumab or traditional treatment group according to whether or not they received belimumab. Renal remission and recurrence rates and glucocorticoid dose were compared between groups. Forty-seven children (median age 11 years) were enrolled, including 30 and 17 children in the traditional treatment and belimumab groups, respectively. The Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2000) score of children in the belimumab group (23.59 ± 7.78) was higher than that in the traditional treatment group (19.13 ± 6.10) (P = 0.035). The two groups showed no significant difference in the frequency of pyuria, gross hematuria, and the levels of 24-h proteinuria and estimated glomerular filtration rate. The complement C3/C4 in the belimumab group recovered faster than that in the traditional treatment group (P < 0.05). There were no between-group differences in the complete renal remission rate at 6 or 12 months (P = 0.442, P = 0.759). There were no between-group differences in 1-year recurrence rate (P = 0.303). Furthermore, 6 and 12 months after treatment, glucocorticoid doses were lower in the belimumab than the traditional treatment group (17.87 ± 6.96 mg/d vs. 27.33 ± 8.40 mg/d, P = 0.000; 10.00 (5.3) mg/d vs. 13.75 (10.0) mg/d, P = 0.007), respectively. CONCLUSION: With an equivalent renal remission rate, belimumab combined with the standard traditional regimen might promote the tapering of glucocorticoids, and the incidence of adverse events is low. WHAT IS KNOWN: ⢠Belimumab is documented as an adjunctive treatment with systemic lupus erythematosus (c-SLE) LN with efficacy. ⢠Due to the paucity of studies, its effects and side effects in children with LN remain unclear. WHAT IS NEW: ⢠This single-center, retrospective cohort study evaluated the efficacy and safety of belimumab combined with the standard regimen in treating children with proliferative LN. ⢠Belimumab combined with the standard traditional treatment might promote the tapering of glucocorticoids, while exhibiting a low occurrence of adverse events.
Assuntos
Anticorpos Monoclonais Humanizados , Quimioterapia Combinada , Glucocorticoides , Imunossupressores , Nefrite Lúpica , Humanos , Nefrite Lúpica/tratamento farmacológico , Feminino , Estudos Retrospectivos , Criança , Masculino , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Imunossupressores/uso terapêutico , Imunossupressores/efeitos adversos , Imunossupressores/administração & dosagem , Glucocorticoides/uso terapêutico , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Adolescente , Resultado do Tratamento , Indução de Remissão/métodos , RecidivaRESUMO
A primary wideband calibration method for noise hydrophones is developed, which can be applied to obtain noise acoustic spectral density sensitivity in the free-field. In this method, a wideband three-transducer spherical wave reciprocity calibration method is proposed in the frequency domain. A lowpass spatial domain filter is utilized to eliminate the reflecting acoustic waves from boundaries and water surface, and the wideband frequency responses of the transducer pair are calculated. Wideband calibrations are performed in a laboratory anechoic water tank, and two hydrophones with different reference sensitivities are calibrated in the frequency range of 250 Hz to 20 kHz using noise signals. The decidecade band sensitivities are obtained by the primary wideband calibration, which is in agreement with the single frequency sensitivities. The expended uncertainty of the primary wideband calibration is analyzed and estimated to be 8.9% (k = 2).
RESUMO
OBJECTIVES: To investigate the incidence and risk factors for acute kidney injury (AKI) in children with primary nephrotic syndrome (PNS), as well as the role of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in the early identification of AKI in these children. METHODS: A prospective collection of clinical data from children hospitalized with PNS at the Children's Hospital of the Capital Institute of Pediatrics from January 2021 to October 2022 was conducted. The children were divided into two groups based on the presence of AKI: the AKI group (47 cases) and the non-AKI group (169 cases). The risk factors for AKI in children with PNS were identified by multivariate logistic regression analysis. Urinary KIM-1 and NGAL levels were compared between the AKI and non-AKI groups, as well as among the different stages of AKI. RESULTS: The incidence of AKI in children with PNS was 21.8%. Multivariate logistic regression analysis revealed that steroid-resistant nephrotic syndrome, gastrointestinal infections, and heavy proteinuria were independent risk factors for AKI in these children with PNS (P<0.05). Urinary KIM-1 and NGAL levels were higher in the AKI group compared to the non-AKI group (P<0.05), and the urinary NGAL and KIM-1 levels in the AKI stage 2 and stage 3 subgroups were higher than those in the AKI stage 1 subgroup (P<0.017). CONCLUSIONS: KIM-1 and NGAL can serve as biomarkers for the early diagnosis of AKI in children with PNS. Identifying high-risk populations for AKI in children with PNS and strengthening the monitoring of related risk factors is of significant importance.
Assuntos
Injúria Renal Aguda , Receptor Celular 1 do Vírus da Hepatite A , Lipocalina-2 , Síndrome Nefrótica , Humanos , Síndrome Nefrótica/complicações , Síndrome Nefrótica/urina , Masculino , Feminino , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/urina , Injúria Renal Aguda/diagnóstico , Pré-Escolar , Criança , Lipocalina-2/urina , Receptor Celular 1 do Vírus da Hepatite A/análise , Fatores de Risco , Estudos Prospectivos , Lactente , Modelos Logísticos , Diagnóstico PrecoceRESUMO
BACKGROUND: The effect of recombinant human GH (rhGH) in Chinese children with chronic kidney disease (CKD) is unclear. METHODS: This was a 52-week, multicenter, randomized, open-label, negative-controlled phase 3 study. Prepubertal subjects were randomized 1:1 to either daily subcutaneous injections of rhGH 0.05 mg/kg/day or no treatment for 52 weeks. RESULTS: A total of 68 subjects with a mean age of 7.8 ± 3.27 years were enrolled. At week 52, the height standard deviation score (HT-SDS) in the treated group increased by 0.75 ± 0.58, which was significantly higher compared with 0.17 ± 0.47 in the untreated group (least squares mean 0.58, 95% confidence interval, 0.32-0.84; P < 0.001). At week 52, significant improvements were observed in other growth parameters (height velocity [P < 0.001]), insulin-like growth factor 1 (IGF-1) SDS [P < 0.001], IFG-1/insulin-like growth factor binding protein-3 molar ratio [P < 0.001], and height [P < 0.001]) compared with the untreated control. Seven patients reported treatment-related adverse events (TRAEs) and most TRAEs were mild in severity. Most subjects recovered without further intervention. CONCLUSIONS: Daily rhGH for 52 weeks in children with CKD-induced growth retardation significantly improved HT-SDS and other growth parameters without compromising safety. IMPACT: The efficacy and safety of growth hormone (GH) therapy in Chinese children with chronic kidney disease (CKD) are unclear. This study found that giving short stature Chinese children with CKD daily recombinant human growth hormone (rhGH) for 52 weeks improved growth parameters without compromising safety. This study's information can give physicians the confidence to treat these patients in their clinical practice.
Assuntos
Hormônio do Crescimento Humano , Insuficiência Renal Crônica , Humanos , Criança , Pré-Escolar , População do Leste Asiático , Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento Humano/uso terapêutico , Hormônio do Crescimento Humano/farmacologia , Hormônio do Crescimento/farmacologia , Insuficiência Renal Crônica/tratamento farmacológico , Fator de Crescimento Insulin-Like I/metabolismo , Proteínas Recombinantes/uso terapêutico , Proteínas Recombinantes/farmacologia , EstaturaRESUMO
OBJECTIVES: To investigate the difference in the therapeutic effect of mycophenolate mofetil (MMF) or cyclophosphamide (CTX) in children with Henoch-Schönlein purpura nephritis (HSPN) of different age groups. METHODS: A retrospective analysis was conducted on the clinical data of 135 children with HSPN who were treated with MMF or CTX in the Department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics, from October 2018 to October 2020. According to the immunosuppressant used, they were divided into two groups: MMF group and CTX group, and according to the age, each group was further divided into two subgroups: ≤12 years and >12 years, producing four groups, i.e, the ≤12 years MMF subgroup (n=30), the >12 years MMF subgroup (n=15), the ≤12 years CTX subgroup (n=71), and the >12 years CTX subgroup (n=19). All children were followed up for at least 12 months, and the above groups were compared in terms of clinical outcomes and the incidence rate of adverse reactions. RESULTS: There was no significant difference in the complete response rate between the MMF group and the CTX group after 3, 6, and 12 months of treatment (P>0.05). There were no significant difference in the complete response rate and the incidence rate of adverse reactions between the >12 years MMF subgroup and the ≤12 years MMF subgroup at 3, 6, and 12 months of treatment (P>0.05). The >12 years CTX subgroup had a significantly lower complete response rate than the ≤12 years CTX subgroup at 6 and 12 months of treatment (P<0.05). The >12 years CTX subgroup had a significantly higher incidence rate of adverse reactions than the >12 years MMF subgroup (P<0.05). CONCLUSIONS: The efficacy and adverse reactions of MMF are not associated with age, but the efficacy of CTX is affected by age, with a higher incidence rate of adverse reactions. CTX should be selected with caution for children with HSPN aged >12 years.
Assuntos
Vasculite por IgA , Nefrite , Vasculite , Criança , Humanos , Ácido Micofenólico/efeitos adversos , Vasculite por IgA/tratamento farmacológico , Estudos Retrospectivos , Ciclofosfamida/efeitos adversos , Imunossupressores/efeitos adversos , Vasculite/induzido quimicamente , Vasculite/complicações , Vasculite/tratamento farmacológico , Nefrite/etiologia , Nefrite/complicaçõesRESUMO
PURPOSE: The extent of myocardial fibrosis is closely related to the prognosis of diabetic cardiomyopathy (DCM). Low-intensity pulsed ultrasound (LIPUS) has been reported to have multiple biological effects. However, the effect of LIPUS on diabetic heart fibrosis remains unclear. The present study aimed to investigate the effect of LIPUS on diabetic heart fibrosis and explore its underlying mechanisms. METHODS AND RESULTS: High glucose (HG) was applied to cultured neonatal rat cardiac fibroblasts (NRCFs) to mimic the in vivo hyperglycemia microenvironment. LIPUS (19.30 mW/cm2 to 77.20 mW/cm2) dose-dependently inhibited HG-induced fibrotic response in NRCFs. Also, LIPUS downregulated NADPH oxidase 4 (NOX4)-associated oxidative stress and nod-like receptor protein-3 (NLRP3) inflammasome activation in NRCFs. In vivo, diabetes in mice was induced with streptozotocin (STZ). Mice in the LIPUS group and STZ + LIPUS group were treated with LIPUS (77.20 mW/cm2) twice a week for 12 weeks and then euthanized at 12 weeks or 24 weeks post-diabetes. Treatment with LIPUS significantly ameliorated the progression of cardiac fibrosis (Masson staining 6.5 ± 2.3% vs. 2.8 ± 1.5%, P < 0.001) and dysfunction (E/A ratio 1.35 ± 0.14 vs. 1.59 ± 0.11, P < 0.05), as well as NOX4-associated oxidative stress (relative expression fold of NOX4 1.43 ± 0.12 vs. 1.07 ± 0.10, P < 0.01; relative DHE fluorescence 1.51 ± 0.13 vs. 1.28 ± 0.06, P < 0.05) and NLRP3 inflammasome activation (relative expression fold of NLRP3 1.57 ± 0.12 vs. 1.05 ± 0.16, P < 0.01), at 12 weeks post-diabetes. At 24 weeks post-diabetes, the heart function in diabetic mice treated with LIPUS was still significantly better than untreated diabetic mice (E/A ratio 1.08 ± 0.12 vs. 1.49 ± 0.14, P < 0.001). Further exploration revealed that LIPUS significantly attenuated the upregulated angiotensin-converting enzyme (ACE) and angiotensin II (AngII), in both HG-induced NRCFs and diabetic hearts (relative expression of ACE in myocardium 3.77 ± 0.55 vs. 1.07 ± 0.13, P < 0.001; AngII in myocardium 115.5 ± 21.77 ng/ml vs. 84.28 ± 9.03 ng/ml, P < 0.01). Captopril, an ACE inhibitor, inhibited NOX4-associated oxidative stress and NLRP3 inflammasome activation in both HG-induced NRCFs and diabetic hearts. CONCLUSION: Our results indicate that non-invasive local LIPUS therapy attenuated heart fibrosis and dysfunction in diabetic mice and the effect could be largely preserved at least 12 weeks after suspending LIPUS stimulation. LIPUS ameliorated diabetic heart fibrosis by inhibiting ACE-mediated NOX4-associated oxidative stress and NLRP3 inflammasome activation in cardiac fibroblasts. Our study may provide a novel therapeutic approach to hamper the progression of diabetic heart fibrosis.
Assuntos
Diabetes Mellitus Experimental , Cardiomiopatias Diabéticas , Acústica , Angiotensina II/metabolismo , Angiotensina II/farmacologia , Animais , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/terapia , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/terapia , Fibroblastos/metabolismo , Fibrose , Inflamassomos/metabolismo , Inflamação , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estresse Oxidativo , RatosRESUMO
We report two cases of HNF1-ß gene variation diagnosed in infancy, in whom fetal ultrasonography revealed enhanced echogenicity and multiple cysts in the renal parenchyma of both patients. They were initially diagnosed as autosomal recessive polycystic kidney disease. Gene testing showed a variation of HNF1-ß gene, one showed chromosome 17q12 deletion including HNF1-ß, the other was a de novo nonsense mutation in the HNF1-ß gene. The two children showed different renal function states. Extrarenal phenotypes also vary widely according to HNF1-ß gene variation including early-onset diabetes, autism spectrum, cognitive disorders, liver function abnormalities, and genital malformations, etc. We emphasize the importance of performing gene detection in order to make an accurate diagnosis, especially in those with fetal hyperechogenic kidneys, and so as to carry out reasonable multidisciplinary management. Early intervention for diabetes and neurodevelopmental disorders are especially important.
Assuntos
Nefropatias , Gravidez , Feminino , Humanos , Nefropatias/genética , Rim/diagnóstico por imagem , Ultrassonografia Pré-Natal , Fenótipo , Testes Genéticos , Fator 1-beta Nuclear de Hepatócito/genéticaRESUMO
OBJECTIVES: To study the clinical effect of full-dose prednisone for 4 or 6 weeks in the treatment of children with primary nephrotic syndrome and its effect on recurrence. METHODS: A prospective non-randomized controlled clinical trial was performed on 89 children who were hospitalized and diagnosed with incipient primary nephrotic syndrome from December 2017 to May 2019. The children were given prednisone of 2 mg/(kg·day) (maximum 60 mg) for 4 weeks (4-week group) or 6 weeks (6-week group), followed by 2 mg/(kg·day) (maximum 60 mg) every other day for 4 weeks and then a gradual reduction in dose until drug withdrawal. The children were regularly followed up for 1 year. The two groups were compared in terms of the indices including remission maintenance time and recurrence rate. A Cox regression analysis was used to assess the risk factors for recurrence. RESULTS: Within 3 months after prednisone treatment, the 4-week group had a significantly higher recurrence rate than the 6-week group (P<0.05). After 1-year of follow-up, there was no significant difference between the two groups in the recurrence rate, remission maintenance time, and recurrence frequency (P>0.05). The risk of recurrence increased in children with an onset age of ≥6 years or increased 24-hour urinary protein (P<0.05). CONCLUSIONS: For the treatment of incipient primary nephrotic syndrome, full-dose prednisone regimen extended from 4 weeks to 6 weeks can reduce recurrence within 3 months. The children with an onset age of ≥6 years or a high level of urinary protein should be taken seriously in clinical practice, and full-dose prednisone treatment for 6 weeks is recommended to reduce the risk of recurrence.
Assuntos
Síndrome Nefrótica , Criança , Glucocorticoides , Humanos , Prednisona , Estudos Prospectivos , Recidiva , Fatores de RiscoRESUMO
OBJECTIVES: To study the clinical effect and adverse drug reactions of different doses of glucocorticoid (GC) in the treatment of children with recurrence of steroid-sensitive nephrotic syndrome (SSNS). METHODS: A total of 67 children who were hospitalized and diagnosed with SSNS recurrence in the Department of Nephrology, Children's Hospital, Capital Institute of Pediatrics, from November 2017 to December 2019 were enrolled. They were randomly divided into a moderate-dose GC group (32 children) and a full-dose GC group (35 children). The two groups were compared in terms of urinary protein clearance, recurrence rate within 6 months, and incidence rate of GC-associated adverse reactions. RESULTS: There was no significant difference in the urinary protein clearance rate between the moderate-dose GC and full-dose GC groups (91% vs 94%, P>0.05). There was also no significant difference in the recurrence rate within 6 months between the two groups (41% vs 36%, P>0.05). At 6 months of follow-up, compared with the full-dose GC group, the moderate-dose GC group had a significantly lower cumulative dose of prednisone [(87±18) mg/kg vs (98±16) mg/kg, P=0.039] and a significantly lower proportion of children with an abnormal increase in body weight (6% vs 33%, P=0.045). The logistic regression analysis showed that prednisone dose ≥10 mg/alternate day at enrollment was a risk factor for recurrence within 6 months in children with SSNS (P=0.018). CONCLUSIONS: For children with SSNS recurrence, moderate-dose GC has similar effects to full-dose GC in the remission induction rate and the recurrence rate within 6 months, with a lower cumulative dose and fewer GC-associated adverse reactions within 6 months than full-dose GC.
Assuntos
Síndrome Nefrótica , Criança , Glucocorticoides/uso terapêutico , Humanos , Síndrome Nefrótica/tratamento farmacológico , Prednisona/efeitos adversos , Estudos Prospectivos , Indução de RemissãoRESUMO
Hypoxia-induced cardiac fibrosis is an important pathological process in cardiovascular disorders. This study aimed to determine whether low-intensity pulsed ultrasound (LIPUS), a novel and safe apparatus, could alleviate hypoxia-induced cardiac fibrosis, and to elucidate the underlying mechanisms. Hypoxia (1% O2 ) and transverse aortic constriction (TAC) were performed on neonatal rat cardiac fibroblasts and mice to induce cardiac fibrosis, respectively. LIPUS irradiation was applied for 20 minutes every 6 hours for a total of 2 times in vitro, and every 2 days from 1 week before surgery to 4 weeks after surgery in vivo. We found that LIPUS dose-dependently attenuated hypoxia-induced cardiac fibroblast phenotypic conversion in vitro, and ameliorated TAC-induced cardiac fibrosis in vivo. Hypoxia significantly upregulated the nuclear protein expression of hypoxia-inducible factor-1α (HIF-1α) and DNA methyltransferase 3a (DNMT3a). LIPUS pre-treatment reversed the elevated expression of HIF-1α, and DNMT3a. Further experiments revealed that HIF-1α stabilizer dimethyloxalylglycine (DMOG) hindered the anti-fibrotic effect of LIPUS, and hampered LIPUS-mediated downregulation of DNMT3a. DNMT3a small interfering RNA (siRNA) prevented hypoxia-induced cardiac fibrosis. Results also showed that the mechanosensitive protein-TWIK-related arachidonic acid-activated K+ channel (TRAAK) messenger RNA (mRNA) expression was downregulated in hypoxia-induced cardiac fibroblasts, and TAC-induced hearts. TRAAK siRNA impeded LIPUS-mediated anti-fibrotic effect and downregulation of HIF-1α and DNMT3a. Above results indicated that LIPUS could prevent prolonged hypoxia-induced cardiac fibrosis through TRAAK-mediated HIF-1α/DNMT3a signalling pathway.
Assuntos
DNA Metiltransferase 3ARESUMO
OBJECTIVE: To study the efficacy and safety of mycophenolate mofetil (MMF) versus cyclophosphamide (CTX) in the treatment of children with Henoch-Schönlein purpura nephritis (HSPN) and nephrotic-range proteinuria. METHODS: A prospective clinical trial was conducted in 68 pediatric patients who were admitted to the Department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics and who were diagnosed with HSPN and nephrotic-range proteinuria from August 2016 to November 2019. The patients were randomly divided into two groups:MMF treatment (n=33) and CTX treatment (n=35). The two groups were compared in terms of complete remission rate, response rate (complete remission + partial remission), urinary protein clearance time, and adverse events. RESULTS: At months 3, 6, and 12 of treatment, there was no significant difference in the complete remission rate and the response rate between the MMF treament and CTX treatment groups (P > 0.05). There was also no significant difference between the two groups in the urinary protein clearance time and the incidence rate of adverse events (P > 0.05). CONCLUSIONS: MMF and CTX have similar efficacy and safety in the treatment of HSPN children with nephrotic-range proteinuria.
Assuntos
Vasculite por IgA , Nefrite , Criança , Ciclofosfamida/efeitos adversos , Humanos , Vasculite por IgA/complicações , Vasculite por IgA/tratamento farmacológico , Imunossupressores/efeitos adversos , Ácido Micofenólico/efeitos adversos , Nefrite/tratamento farmacológico , Estudos Prospectivos , Proteinúria/tratamento farmacológico , Proteinúria/etiologia , Estudos RetrospectivosRESUMO
Acoustic droplet vaporization (ADV) is an important process that enables the theragnostic application of acoustically activated droplets, where the nucleation of inertial cavitation (IC) activity must be precisely controlled. This Letter describes threshold pressure measurements for ADV and acoustic emissions consistent with IC activity of lipid-shelled non-superheated perfluoropentane nanodroplets over a range of physiologically relevant concentrations at 1.1-MHz. Under the frequency investigated, results show that the thresholds were relatively independent of concentration for intermediate concentrations (105, 106, and 107 droplets/ml), thus indicating an optimal range of droplet concentrations for conducting threshold studies. For the highest concentration, the difference between the threshold for IC and the threshold for ADV was greatly reduced, suggesting that it might prove difficult to induce ADV without concomitant IC in applications that employ higher concentrations.
RESUMO
OBJECTIVES: A long-circulating lipid-coated ultrasound (US) contrast agent was fabricated to achieve a longer wash-out time and gain more resistance against higher-mechanical index sonication. Systemic physical, acoustic, and in vivo imaging experiments were performed to better understand the underlying mechanism enabling the improvement of contrast agent performance by adjusting the physical and acoustic properties of contrast agent microbubbles. METHODS: By simply altering the gas core, a kind of US contrast agent microbubble was synthesized with a similar lipid-coating shell as SonoVue microbubbles (Bracco SpA, Milan, Italy) to achieve a longer wash-out time and higher inertial cavitation threshold. To bridge the structure-performance relationship of the synthesized microbubbles, the imaging performance of the microbubbles was assessed in vivo with SonoVue as a control group. The size distribution and inertial cavitation threshold of the synthesized microbubbles were characterized, and the shell parameters of the microbubbles were determined by acoustic attenuation measurements. All of the measurements were compared with SonoVue microbubbles. RESULTS: The synthesized microbubbles had a spherical shape, a smooth, consistent membrane, and a uniform distribution, with an average diameter of 1.484 µm. According to the measured attenuation curve, the synthesized microbubbles resonated at around 2.8 MHz. Although the bubble's shell elasticity (0.2 ± 0.09 N/m) was comparable with SonoVue, it had relatively greater viscosity and inertial cavitation because of the different gas core. Imaging studies showed that the synthesized microbubbles had a longer circulation time and a better chance of fighting against rapid collapse than SonoVue. CONCLUSIONS: Nano/micrometer long-circulating lipid-coated microbubbles could be fabricated by simply altering the core composition of SonoVue microbubbles with a higher-molecular weight gas. The smaller diameter and higher inertial cavitation threshold of the synthesized microbubbles might make it easier to access deep-seated organs and give prolonged imaging enhancement in the liver.
Assuntos
Meios de Contraste/farmacocinética , Aumento da Imagem/métodos , Lipídeos , Neoplasias Hepáticas Experimentais/diagnóstico por imagem , Microbolhas , Ultrassonografia/métodos , Acústica , Animais , Modelos Animais de Doenças , Humanos , Camundongos , Fosfolipídeos/farmacocinética , Ratos , Hexafluoreto de Enxofre/farmacocinética , TransdutoresRESUMO
Wilson's disease (WD) is an autosomal recessive disorder, and has a variety of presentations. We reported a case of 9-year-old girl who presented with a history of recurrent gross hematuria, renal histological changes of IgA nephropathy, and finally had been confirmed to be Wilson's disease-associated IgA nephropathy.
Assuntos
Hematúria/etiologia , Degeneração Hepatolenticular/complicações , Pré-Escolar , Feminino , Degeneração Hepatolenticular/tratamento farmacológico , Degeneração Hepatolenticular/patologia , Humanos , Rim/patologia , Proteinúria/urina , Sulfato de Zinco/administração & dosagemRESUMO
Acoustic standing waves have been widely used in trapping, patterning, and manipulating particles, whereas one barrier remains: the lack of understanding of force conditions on particles which mainly include acoustic radiation force (ARF) and acoustic streaming (AS). In this paper, force conditions on micrometer size polystyrene microspheres in acoustic standing wave fields were investigated. The COMSOL® Mutiphysics particle tracing module was used to numerically simulate force conditions on various particles as a function of time. The velocity of particle movement was experimentally measured using particle imaging velocimetry (PIV). Through experimental and numerical simulation, the functions of ARF and AS in trapping and patterning were analyzed. It is shown that ARF is dominant in trapping and patterning large particles while the impact of AS increases rapidly with decreasing particle size. The combination of using both ARF and AS for medium size particles can obtain different patterns with only using ARF. Findings of the present study will aid the design of acoustic-driven microfluidic devices to increase the diversity of particle patterning.
RESUMO
OBJECTIVES: Percutaneous ethanol ablation (PEA) is an effective method for treating small liver cancer. Microbubble-enhanced ultrasound (MEUS) can potentially promote PEA by disrupting the tumour's circulation. In this study, treatment combining MEUS and PEA was performed to find any synergistic effects in tumour ablation. METHODS: Ten rats bearing subcutaneous Walker-256 tumours were treated by MEUS combined with PEA. The other 18 tumour-bearing rats that were treated by MEUS or PEA served as the controls. MEUS was conducted by therapeutic ultrasound (TUS) and microbubble injection. TUS was operated at a frequency of 831 KHz with a pressure amplitude of 4.3 MPa. Tumour blood perfusion was assessed by contrast-enhanced ultrasound (CEUS), and the tumour necrosis rate was determined by histological examination. RESULTS: CEUS showed that the tumour blood perfusion almost vanished in all of the MEUS-treated tumours. The contrast peak intensity dropped 84.8 % in the MEUS + PEA-treated tumours when compared to 46.3 % (p < 0.05) in the PEA-treated tumours 24 h after treatment. The tumour necrosis rate of the combination therapy was 97.50 %, which is much higher than that of the MEUS- (66.2 %) and PEA-treated (81.0 %) tumours. CONCLUSION: PEA combined with MEUS can induce a much more complete tumour necrosis. KEY POINTS: ⢠This experiment demonstrated a novel method for enhancing percutaneous ethanol ablation. ⢠Microbubble-enhanced therapeutic ultrasound is capable of disrupting tumour circulation. ⢠Combined therapy of MEUS and PEA can induce more complete necrosis of tumours.
Assuntos
Carcinoma 256 de Walker/terapia , Meios de Contraste , Etanol/administração & dosagem , Ondas de Choque de Alta Energia/uso terapêutico , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Microbolhas/uso terapêutico , Escleroterapia/métodos , Animais , Linhagem Celular Tumoral , Terapia Combinada/métodos , Feminino , Aumento da Imagem/métodos , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To study the efficacy of Huai Qi Huang granules in the treatment of childhood primary nephrotic syndrome. METHODS: Between July 2009 and December 2011, patients who were admitted and diagnosed for the first time as childhood primary nephrotic syndrome were randomized into a treatment group (Huai Qi Huang granules plus glucocorticoid; n=23) and a control group (glucocorticoid alone; n=19) for a prospective study. The two groups were compared for regression time of edema, time to urinary protein clearance, relapse rate, incidence of infection, dosage of glucocorticoid, and humoral and cellular immunological indicators. RESULTS: There were no significant differences in regression time of edema, time to urinary protein clearance, and relapse rate between the treatment and control groups (P>0.05). The treatment group had significantly lower incidence of infection and daily dose of glucocorticoid (at month 6) than the control group (P<0.05). Humoral and cellular immunological indicators showed no significant differences between the two groups (P>0.05). No Huai Qi Huang-related adverse events were observed in this study. CONCLUSIONS: Huai Qi Huang granules treatment can reduce the dose of glucocorticoid and the incidence of infection in children with primary nephrotic syndrome and has a favourable safety.
Assuntos
Astragalus propinquus , Medicamentos de Ervas Chinesas/uso terapêutico , Síndrome Nefrótica/tratamento farmacológico , Criança , Pré-Escolar , Feminino , Glucocorticoides/uso terapêutico , Humanos , Lactente , Masculino , Estudos ProspectivosRESUMO
Sonodynamic therapy (SDT) has emerged as a novel and highly researched advancement in the medical field. Traditional ultrasound contrast agents and novel bubble-shaped agents are used to stimulate cavitation and enhance SDT efficiency. However, the impact of artificially modified shell structures on the acoustic properties of microbubbles remains to be explored. Alternatively, in the absence of bubble-shaped agents, some clinically available organic sonosensitizers and advanced inorganic materials are also used to enhance the efficacy of SDT. Diagnostic and therapeutic ultrasound can also activate cavitation bubbles, which supply energy to sonosensitive agents, leading to the production of cytotoxic free radicals to achieve therapeutic effects. While inorganic materials often spark controversy in clinical applications, their relatively simple structure enables researchers to gain insight into the mechanism by which SDT produces various free radicals. Some organic-inorganic hybrid sonosensitive systems have also been reported, combining the benefits of inorganic and organic sonosensitive agents. Alternatively, by employing cell surface modification engineering to enable cells to perform functions such as immune escape, drug loading, gas loading, and sonosensitivity, cellular sonosensitizers have also been developed. However, further exploration is needed on the acoustic properties, ability to generate reactive oxygen species (ROS), and potential clinical application of this cellular sonosensitizer. This review offers a comprehensive analysis of vesical microbubbles and nanoscale sonocatalysts, including organic, inorganic, combined organic-inorganic sonosensitizers, and cellular sonosensitizers. This analysis will enhance our understanding of SDT and demonstrate its important potential in transforming medical applications.