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BACKGROUND: Split kidney function (SKF) is critical for treatment decision in pediatric patients with hydronephrosis and is commonly measured using renal scintigraphy (RS). Non-contrast-enhanced magnetic resonance urography (NCE-MRU) is increasingly used in clinical practice. This study aimed to investigate the feasibility of using NCE-MRU as an alternative to estimate SKF in pediatric patients with hydronephrosis, compared to RS. METHODS: Seventy-five pediatric patients with hydronephrosis were included in this retrospective study. All patients underwent NCE-MRU and RS within 2 weeks. Kidney parenchyma volume (KPV) and texture analysis parameters were obtained from T2-weighted (T2WI) in NCE-MRU. The calculated split KPV (SKPV) percent and texture analysis parameters percent of left kidney were compared with the RS-determined SKF. RESULTS: SKPV showed a significant positive correlation with SKF (r = 0.88, p < 0.001), while inhomogeneity was negatively correlated with SKF (r = - 0.68, p < 0.001). The uncorrected and corrected prediction models of SKF were established using simple and multiple linear regression. Bland-Altman plots demonstrated good agreement of both predictive models. The residual sum of squares of the corrected prediction model was lower than that of the uncorrected model (0.283 vs. 0.314) but not statistically significant (p = 0.662). Subgroup analysis based on different MR machines showed correlation coefficients of 0.85, 0.95, and 0.94 between SKF and SKPV for three different scanners, respectively (p < 0.05 for all). CONCLUSIONS: NCE-MRU can be used as an alternative method for estimating SKF in pediatric patients with hydronephrosis when comparing with RS. Specifically, SKPV proves to be a simple and universally applicable indicator for predicting SKF.
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Hidronefrose , Urografia , Criança , Humanos , Estudos Retrospectivos , Urografia/métodos , Hidronefrose/diagnóstico por imagem , Rim/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Cintilografia , Espectroscopia de Ressonância MagnéticaRESUMO
BACKGROUND AND PURPOSE: The classic Shamblin system fails to provide valuable guidance in many Shamblin's III carotid body tumors (III-CBTs) due to the variable forms of carotid arteries and the complex anatomic relationships in parapharyngeal space. We proposed a modified classification to separately divide III-CBTs into different subgroups on the basis of arterial relevant features and anatomical relevant features. MATERIALS AND METHODS: From 2020 to 2023, a total of 129 III-CBTs at a single institution were retrospectively analyzed. All cases were independently classified as arterial-relevant and anatomical-relevant subgroups. The pre-, peri- and postoperative data were summarized and compared accordingly. RESULTS: Among the 129 cases, 69 cases were identified as "Classical type", 23 cases as "Medial type", 27 cases as "Lateral type" and 10 cases as "Enveloped type" according to arterial morphologies. Besides, 76 cases were identified as "Common type", 15 cases as "Pharynx- invasion type", 18 cases as "Skull base-invasion type" and 20 cases as "Mixed type" according to anatomical relationships. "Enveloped type" of tumors in arterial-relevant classification and "Mixed type" of tumors in anatomical-relevant classification are the most challenging cases for surgeons with the lowest resection rate, highest incidence of carotid arteries injury and postoperative stroke. CONCLUSION: The modified classifications provide comprehensive understanding of different III-CBTs which are applicable for individualized treatment in clinical practice.
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Tumor do Corpo Carotídeo , Humanos , Tumor do Corpo Carotídeo/cirurgia , Tumor do Corpo Carotídeo/patologia , Estudos Retrospectivos , Procedimentos Cirúrgicos Vasculares , Artérias Carótidas/patologia , Incidência , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVES: If the proportion of calcium intake over a whole day is related to the risk of cognitive impairment in adults is still largely unknown. This research aimed to examine the relation of dietary calcium intake at dinner versus breakfast with the risk of cognitive impairment by using data from the China Health and Nutrition Survey (CHNS). METHODS AND STUDY DESIGN: A total of 2,099 participants (including 668 cognitive impairment) in the CHNS (1997-2006) were included. The participants were categorized into 5 groups in accordance with the ratio of dietary calcium intake at dinner and breakfast (Δ = dinner/breakfast). After adjustment was conducted for a series of confounding factors, Cox hazard regression modelling was performed to discuss the relation of Δ with cognitive impairment. Dietary substitution models were used to explore the changes in cognitive impairment risk when a 5% dietary calcium intake at dinner was replaced with dietary calcium intake at breakfast. RESULTS: Participants in the highest distribution of Δ showed a greater susceptibility to cognitive impairment than those in the lowest quintile, with an adjusted hazard ratio of cognitive impairment of 1.38 (95% CI: 1.08-1.76). When maintaining total calcium intake, substituting 5% of dietary calcium intake at dinner with calcium intake at breakfast was related to an 8% decrease in the risk of cognitive impairment. CONCLUSIONS: Higher dietary calcium intake at dinner was associated with an increased risk of cognitive impairment, emphasizing the importance of appropriately distributing dietary calcium intake between breakfast and dinner.
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Desjejum , Cálcio da Dieta , Disfunção Cognitiva , Humanos , Cálcio da Dieta/administração & dosagem , Masculino , Feminino , China/epidemiologia , Pessoa de Meia-Idade , Disfunção Cognitiva/epidemiologia , Estudos de Coortes , Adulto , Refeições , Inquéritos Nutricionais , Idoso , Fatores de Risco , População do Leste AsiáticoRESUMO
Post-transplant lymphoproliferative disorder (PTLD) is a common secondary malignancy after transplantation, which has been recognized as a life-threatening complication. Hodgkin lymphoma (HL)-type PTLD is the rarest of four subtypes of PTLD, which has no treatment guideline due to its rarity. HL-type PTLD includes classical HL-type PTLD (cHL-PTLD) and HL-like PTLD. In our study, we reported the case of successful treatment using brentuximab vedotin (BV) plus sirolimus for a patient with classical HL-type PTLD in detail. Lymph node biopsy showed a picture of classical HL with mixed cellularity subtype, and immunophenotyping suggested CD30 strong positivity. Due to his impaired physical condition, we decided against intensive chemotherapy and started BV treatment with immunosuppressive agents switched to sirolimus. The 66-year-old patient with cHL-PTLD had achieved a durable complete remission for over a 1-year follow-up period. Additionally, we analyzed the clinical profile and outcomes in PTLD patients who used BV monotherapy or combined therapy by literature review. In summary, this case-based review might provide clues that treatment of cHL-PTLD with new modalities such as BV monotherapy or combination therapy, together with improvements in the immunosuppressive regimens like sirolimus, might be a feasible and chemotherapy-free approach, but warrants further evaluation in a larger patient cohort.
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Turmeric was the dried rhizome of Curcuma longa L., and its extract had important pharmacological effects such as anti-tumor, cholagogic, and antioxidant. However, curcuma extract had poor water solubility and low bioavailability, which had become the main limiting factor for its clinical application. The purpose of this study was to prepare PVP/VA-Poloxamer-188-curcuma extract solid dispersion (PAP-CSD) to improve the solubility and bioavailability of the curcuma extract. The intestinal absorption mechanism of solid dispersion of this extract was studied by one-way intestinal perfusion in rats. PAP-CSD,PVP/VA-curcuma extract solid dispersion (PA-CSD) and Poloxamer-188-curcuma extract solid dispersion (P-CSD) was able to improve the intestinal absorption of the curcuma extract (P < 0.05), and PAP-CSD (combined use of two carriers) was better than that of PA-CSD and P-CSD. CCK8 method was used to investigate the effects of the curcuma extract and PAP-CSD on the proliferation of hepatic stellate cells (HSC)-T6 cells. The inhibitory effect of PAP-CSD on the proliferation of HSC-T6 cells, related to the p38 MAPK pathway, was better than that of the curcuma extract.
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Curcuma , Poloxâmero , Animais , Proliferação de Células , Perfusão , Extratos Vegetais/farmacologia , RatosRESUMO
Root exudation stimulates microbial decomposition and enhances nutrient availability to plants. It remains difficult to measure and predict this carbon flux in natural conditions, especially for mature woody plants. Based on a known conceptual framework of root functional traits coordination, we proposed that root functional traits may predict root exudation. We measured root exudation and other seven root morphological/chemical/physiological traits for 18 coexisting woody species in a deciduous-evergreen mixed forest in subtropical China. Root exudation, respiration, diameter and nitrogen (N) concentration all exhibited significant phylogenetic signals. We found that root exudation positively correlated with competitive traits (root respiration, N concentration) and negatively with a conservative trait (root tissue density). Furthermore, these relationships were independent of phylogenetic signals. A principal component analysis showed that root exudation and morphological traits loaded on two perpendicular axes. Root exudation is a competitive trait in a multidimensional fine-root functional coordination. The metabolic dimension on which root exudation loaded was relatively independent of the morphological dimension, indicating that increasing nutrient availability by root exudation might be a complementary strategy for plant nutrient acquisition. The positive relationship between root exudation and root respiration and N concentration is a promising approach for the future prediction of root exudation.
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Florestas , Raízes de Plantas , China , Nitrogênio , FilogeniaRESUMO
Carotid jugular fistula and pseudoaneurysm are easy to form after gunshot injury of carotid artery. Endovascular therapy, such as stent graft implantation, can successfully block the fistula and pseudoaneurysm cavity. However, the possibility of in-stent restenosis or occlusion will lead to treatment failure. The authors describe the case of a 30-year-old man with carotid jugular fistula and pseudoaneurysm after gunshot injury of left carotid artery who had received stent graft placement. However, two years after stent graft, the stenosis of proximal carotid artery near stent was found and gradually aggravated. During the follow-up, transient amaurosis of his left eye occurred intermittently and in-stent occlusion and severe stenosis of proximal carotid artery were found by computed tomography angiography (CTA) in our center. Carotid endarterectomy (CEA)with stent graft removal and end to end bypass using vascular graft was performed to reconstruct the blood flow of left carotid artery. To the extent of the authors' knowledge, this case illustrates a rare CEA and vascular graft bypass in the treatment of in-stent occlusion following the gunshot injury to the carotid artery. The successful treatment of this rare case provides an option to deal with this kind of tricky problem.
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Falso Aneurisma/cirurgia , Fístula Arteriovenosa/cirurgia , Implante de Prótese Vascular/efeitos adversos , Lesões das Artérias Carótidas/cirurgia , Estenose das Carótidas/cirurgia , Remoção de Dispositivo , Endarterectomia das Carótidas , Procedimentos Endovasculares/efeitos adversos , Oclusão de Enxerto Vascular/cirurgia , Ferimentos por Arma de Fogo/cirurgia , Adulto , Falso Aneurisma/diagnóstico por imagem , Fístula Arteriovenosa/diagnóstico por imagem , Prótese Vascular , Implante de Prótese Vascular/instrumentação , Lesões das Artérias Carótidas/diagnóstico por imagem , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/etiologia , Procedimentos Endovasculares/instrumentação , Oclusão de Enxerto Vascular/diagnóstico por imagem , Oclusão de Enxerto Vascular/etiologia , Humanos , Masculino , Stents , Resultado do Tratamento , Ferimentos por Arma de Fogo/diagnóstico por imagemRESUMO
Arbuscular mycorrhizal (AM) fungi play important roles in carbon (C), nitrogen (N) and phosphorus (P) cycling of terrestrial ecosystems. The impact of increasing N deposition on AM fungi will inevitably affect ecosystem processes. However, generalizable patterns of how N deposition affects AM fungi remains poorly understood. Here we conducted a global-scale meta-analysis from 94 publications and 101 sites to investigate the responses of AM fungi to N addition, including abundance in both intra-radical (host roots) and extra-radical portion (soil), richness and diversity. We also explored the mechanisms of N addition affecting AM fungi by the trait-based guilds method. Results showed that N addition significantly decreased AM fungal overall abundance (-8.0%). However, the response of abundance in intra-radical portion was not consistent with that in extra-radical portion: root colonization decreased (-11.6%) significantly, whereas extra-radical hyphae length density did not change significantly. Different AM fungal guilds showed different responses to N addition: both the abundance (spore density) and relative abundance of the rhizophilic guild decreased significantly under N addition (-29.8% and -12.0%, respectively), while the abundance and relative abundance of the edaphophilic guild had insignificant response to N addition. Such inconsistent responses of rhizophilic and edaphophilic guilds were mainly moderated by the change of soil pH and the response of root biomass, respectively. Moreover, N addition had an insignificant negative effect on AM fungal richness and diversity, which was strongly related with the relative availability of soil P (i.e. soil available N/P ratio). Collectively, this meta-analysis highlights that considering trait-based AM fungal guilds, soil P availability and host plant C allocation can greatly improve our understanding of the nuanced dynamics of AM fungal communities under increasing N deposition.
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Micorrizas , Ecossistema , Fungos , Nitrogênio , Raízes de Plantas , Solo , Microbiologia do SoloRESUMO
Nitric oxide (NO) is known to be a secondary in vivo signaling agent, demonstrating various biological functions through regulating ion flux in channels. Considering the crucial role of NO in vivo, herein, a biomimetic NO-regulated nanofluidic sensor has been fabricated through a cyclization reaction strategy. This nanofluidic sensor exhibited a promising NO selectivity, sensitivity, and non-interference performance in complex matrices. Thus, such a NO-driven nanosensor will be meaningful for scientific researchers to grasp the in vivo functions of NO.
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BACKGROUND: Formulae of estimated glomerular filtration rate (eGFR) based on serum creatinine (Scr) are routinely used in oncology patients, however, they are inaccurate in some populations. Our aim was to assess the agreement of eGFR formulae and thereby build a nomogram to predict the reliability of estimates. METHODS: Measured GFR (mGFR) using isotope from 445 oncology patients were compared with eGFR from six formulae (Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), modified MDRD formulae for Chinese (C-MDRD), Chronic Kidney Disease Epidemiology (CKD-EPI) Collaboration, Wright and full age spectrum (FAS)). Bias, precision and accuracy of eGFR formulae were examined. We also evaluated statistics of agreement: the total deviation index (TDI), the concordance correlation coefficient (CCC) and the coverage probability (CP). Multivariate logistic regression was applied to identify characteristics associated with inaccurate eGFR and construct a predictive nomogram. RESULTS: All eGFR formulae tended to overestimate the eGFR. The percentage of patients with eGFR within 30% the mGFR ranged from 38.0 to 62.8%. Cockcroft-Gault and MDRD showed low bias and high precision. The MDRD formula exhibited lowest TDI, meaning that 90% of estimations ranged from - 36 to 36% of mGFR. Multivariate logistic regression showed that inaccuracy of MDRD was found in elderly patients or in patients with eGFR greater than 120 ml/min. A nomogram was constructed to help oncologists to predict the risk of inaccuracy of eGFR. The calibration curve showed good agreement. CONCLUSIONS: Our results suggest that the error of eGFR by any formulae was common and wide in Chinese oncology patients. Our nomogram may assist oncologists in decision-making when mGFR is needed.
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Taxa de Filtração Glomerular/fisiologia , Testes de Função Renal/métodos , Neoplasias/complicações , Nomogramas , Insuficiência Renal/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Creatinina/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/fisiopatologia , Valor Preditivo dos Testes , Insuficiência Renal/sangue , Insuficiência Renal/etiologia , Insuficiência Renal/fisiopatologia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: MiR-499 has been reported to be expressed only in cardiomyocytes, and its expression would increase after acute myocardial infarction (AMI). miR-499 plays a role in the process of cardiomyocytes injury induced by hypoxia/reoxygenation (H/R), however, it still remains unclear. RESULTS: Hypoxia inhibited miR-499-5p expression and H/R induced apoptosis. SOX6 was a target gene of miR-499-5p, and high expression of miR-499-5p inhibited the expression of SOX6. MiR-499-5p reduced H9c2 cells injury by inhibiting the expression of SOX6, overexpression of which could reverse the effect of miR-499-5p on H9c2 cells. MiR-499-5p inhibited the levels of LDH and MDA, while overexpression of miR-499-5p inhibited H/R-induced cell apoptosis. MiR-499-5p could up-regulate the level of Bcl-2 and down-regulate the expression levels of Bax and caspase-3. However, SOX6 partially reversed these effects of miR-499-5p. CONCLUSION: We proved that miR-499-5p inhibited H/R-induced cardiomyocytes injury by targeting SOX6. Our results suggested that miR-499-5p/SOX6 pathway may present a potential therapeutic target for the treatment of AMI.
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Hipóxia , MicroRNAs/metabolismo , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miócitos Cardíacos/metabolismo , Fatores de Transcrição SOXD/metabolismo , Animais , Sobrevivência Celular , RatosRESUMO
PURPOSE: Schisanhenol is a compound derived from the fruit of a traditional Chinese herb Schisandra rubriflora. The aim of the present study was to evaluate the effect of Schisanhenol on the cognitive impairment induced by scopolamine. MATERIAL AND METHODS: Male mice were randomly divided into three Schisanhenol groups (10, 30, 100 mg/kg), Galantamine group (3 mg/kg), model group (1mg/kg scopolamine), and vehicle control group (normal saline). The learning and memory ability of mice was monitored by water morris maze. Hippocampus of mice were collected after behavioral testing and the activity of SOD, MDA, GSH-px, AChE were measured with standard biochemical procedures. Western blotting was used to analyze the expression of SIRT1, PGC-1α, phosphorylated Tau proteins. RESULTS: Intraperitoneal administration of Schisanhenol (10, 30 or 100 mg/kg) significantly attenuated scopolamine-induced cognitive impairment in water morris maze. In addition, Schisanhenol increased the activity of SOD and GSH-px while decreased the content of AChE and MDA. Furthermore, western blotting analysis revealed that Schisanhenol increased the levels of SIRT1 and PGC-1α and decreased the level of phosphorylated Tau protein (Ser 396) significantly in the hippocampal tissues. CONCLUSIONS: Our findings indicated that Schisanhenol can attenuate scopolamine-induced learning impairment and enhance cognitive function, the mechanism via improve the cholinergic system and antioxidant ability, activate SIRT1-PGC1α signaling, inhibit the phosphorylation of Tau, and would be an effective candidate against cognitive disorders, such as Alzheimer's disease.
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Acetilcolinesterase/metabolismo , Ciclo-Octanos/administração & dosagem , Hipocampo/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Compostos Policíclicos/administração & dosagem , Sirtuína 1/metabolismo , Proteínas tau/metabolismo , Animais , Hipocampo/metabolismo , Masculino , Memória/efeitos dos fármacos , Camundongos , Estresse Oxidativo , Escopolamina/administração & dosagem , Transdução de SinaisRESUMO
Universal salt iodisation (USI) has been successfully implemented in China for more than 15 years. Recent evidence suggests that the definition of 'adequate iodine' (100-199 µg/l) be revised to 'sufficient iodine' (100-299 µg/l) based on the median urinary iodine concentration (MUI) in school-age children. The objective of this study was to determine the prevalence of thyroid dysfunction in populations after long-term salt iodisation and examine whether the definition of adequate iodine can be broadened to sufficient iodine based on the thyroid function in four population groups. A cross-sectional survey was conducted in six provinces in the northern, central and southern regions of China. Four population groups consisting of 657 children, 755 adults, 347 pregnant women and 348 lactating women were recruited. Three spot urinary samples were collected over a 10-d period and blood samples were collected on the 1st day. In the study, among the adults, pregnant women and lactating women, the prevalence rates of elevated thyroglobulin antibody and thyroid microsomal antibody levels were 12·4, 8·5 and 7·8 %, and 12·1, 9·1 and 9·1 %, respectively. Abnormally high thyroid dysfunction prevalence was not observed after more than 15 years of USI in China because the thyroid dysfunction rates were all <5 %. The recommended range should be cautiously broadened from adequate iodine to sufficient iodine according to the MUI of school-age children considering the high levels of hormones and antibodies in the other populations. Adults, particularly pregnant women positive for thyroid antibodies, should be closely monitored.
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Autoanticorpos/sangue , Iodo/administração & dosagem , Lactação/fisiologia , Cloreto de Sódio na Dieta/administração & dosagem , Glândula Tireoide/efeitos dos fármacos , Adolescente , Adulto , Criança , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Hipotireoidismo/epidemiologia , Hipotireoidismo/prevenção & controle , Iodo/urina , Masculino , Pessoa de Meia-Idade , Gravidez , Tireoglobulina/imunologia , Glândula Tireoide/fisiologia , Adulto JovemRESUMO
BACKGROUND: Major depressive disorder (MDD) is a common mental disorder worldwide, but now there is a lack of clinically effective assessment and management of MDD. In this study, we used technetium-99 m ethylcysteinate dimer ([99mTc]ECD) SPECT/CT to characterize the regional cerebral blood flow (rCBF) status of MDD patients, and to explore an objective image assessment model of MDD which is non- or minimally-invasive, convenient and accurate in a clinical setting. METHODS: The severity of MDD was assessed by three trained psychiatrists, based on scores obtained from HAMD and HAMA. [99mTc]ECD rCBF SPECT/CT was performed in 20 healthy controls and 74 unipolar MDD patients before receiving the treatment. The CT attenuation-corrected SPECT images data were automatically registered, analyzed simultaneously by 3D-SSP and eZIS. RESULTS: The mean score of HAMD and HAMA in the MDD patients was 25.49 ± 6.00, and 23.12 ± 5.83, respectively. There was a positive correlation between two scores. The MDD women had higher HAMD scores than MDD men. The decreased rCBF of MDD patients in frontal lobes (bilateral B11, B47 and right B4, B6, B10, B46), temporal lobe (right B21, B41, B42) and cingulated cortex (bilateral B24, B33), while their increased rCBF in occipital lobe (bilateral B17, B19 and left B18). Additionally, the depression severity was negatively correlated with decreased rCBF in left ventral anterior cingulate cortex B24, and was positively correlated with decreased rCBF in left inferior prefrontal gyrus B47 and increased rCBF in right associative visual cortex B19. The anxiety severity was negatively correlated with decreased rCBF in left subgenual cortex B25. CONCLUSIONS: Although the mechanism underlying the correlation is not yet fully understood, our findings indicated that the rCBF SPECT/CT may provide an objective assessment for MDD severity. It might be used monitoring therapeutic efficacy in the management of MDD.
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Mapeamento Encefálico/métodos , Córtex Cerebral/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Índice de Gravidade de Doença , Adulto , Córtex Cerebral/patologia , Circulação Cerebrovascular , Cisteína/análogos & derivados , Feminino , Lobo Frontal/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Compostos de Organotecnécio , Lobo Temporal/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Pneumocephalus after posterior fossa craniotomy is very common. However, cranial nerve dysfunction secondary to pneumocephalus is a very rare phenomenon. PATIENT PRESENTATION: This case reports a patient who suffers from Chiari I malformation with syringomyelia in cervical spinal cord and develops unilateral oculomotor nerve palsy after atlanto-occipital decompression with dural plasty. CONCLUSIONS: Cranial nerve dysfunction caused by pneumocephalus after craniotomy is rare and easily misdiagnosed. Timely head computed tomography or magnetic resonance imaging examination can exclude other causes and reveal the anatomic sites of pneumocephalus. Conservative treatment is available in most patients while sometimes it is necessary to drain the air.
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Descompressão Cirúrgica/efeitos adversos , Doenças do Nervo Oculomotor/etiologia , Pneumocefalia/complicações , Adulto , Malformação de Arnold-Chiari/complicações , Tratamento Conservador/métodos , Craniotomia/efeitos adversos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pneumocefalia/cirurgia , Siringomielia/cirurgia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is a primary liver tumor and is the most difficult human malignancy to treat. In this study, we sought to develop an integrative approach in which real-time tumor monitoring, gene therapy, and internal radiotherapy can be performed simultaneously. This was achieved through targeting HCC with superparamagnetic iron oxide nanoparticles (SPIOs) carrying small interfering RNA with radiolabled iodine 131 (131I) against the human vascular endothelial growth factor (hVEGF). METHODS: hVEGF siRNA was labeled with 131I by the Bolton-Hunter method and conjugated to SilenceMag, a type of SPIOs. 131I-hVEGF siRNA/SilenceMag was then subcutaneously injected into nude mice with HCC tumors exposed to an external magnetic field (EMF). The biodistribution and cytotoxicity of 131I-hVEGF siRNA/SilenceMag was assessed by SPECT (Single-Photon Emission Computed Tomography) and MRI (Magnetic Resonance Imaging) studies and blood kinetics analysis. The body weight and tumor size of nude mice bearing HCC were measured daily for the 4-week duration of the experiment. RESULTS: 131I-hVEGF siRNA/SilenceMag was successfully labeled; with a satisfactory radiochemical purity (>80%) and biological activity in vitro. External application of an EMF successfully attracted and retained more 131I-hVEGF siRNA/SilenceMag in HCC tumors as shown by SPECT, MRI and biodistribution studies. The tumors treated with 131I-hVEGF siRNA/SilenceMag grew nearly 50% slower in the presence of EMF than those without EMF and the control. Immunohistochemical assay confirmed that the tumor targeted by 131I-hVEGF siRNA/SilenceMag guided by an EMF had a lower VEGF protein level compared to that without EMF exposure and the control. CONCLUSIONS: EMF-guided 131I-hVEGF siRNA/SilenceMag exhibited an antitumor effect. The synergic therapy of 131I-hVEGF siRNA/SilenceMag might be a promising future treatment option against HCC with the dual functional properties of tumor therapy and imaging.
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Carcinoma Hepatocelular/terapia , Compostos Férricos/administração & dosagem , Neoplasias Hepáticas/terapia , Nanopartículas Metálicas/administração & dosagem , RNA Interferente Pequeno/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/administração & dosagem , Animais , Carcinoma Hepatocelular/patologia , Células Hep G2 , Humanos , Radioisótopos do Iodo/administração & dosagem , Neoplasias Hepáticas/patologia , Magnetoterapia/métodos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Distribuição Aleatória , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
OBJECTIVE: To determine predictors for in-stent restenosis (ISR) within 2 years after drug-eluting stent (DES) implantation in coronary heart disease patients complicating with diabetes mellitus and to establish predictive model. METHODS: We retrospectively analyzed clinical data of patients underwent DES implantation in our hospital between January 2005 and December 2012. Using random number generated by SPSS 17.0, a total of 3 073 cases were randomly divided into two cohort, model derivation cohort (MDC) and model validation cohort (MVC). MDC (2 048 cases) was divided into in-stent restenosis (ISR) group and control group. Predictors were identified using univariable and multivariable logistic regression analysis in MDC. Integer point values were assigned to each predictor based upon their ß coefficient in multivariable logistic regression model to establish scoring model. The summed scores of each case in MVC (1 025 cases) were calculated to test predictive ability of the model. RESULTS: Of all these 3 073 cases, 217 cases (7.1%) were diagnosed with ISR within 2 year after DES implantation. The incidence of ISR within 2 year after DES implantation was 7.3% (149 cases) in MDC and logistic regression analysis identified six ISR risk factors: multiple target vessels (OR = 3.69, 95%CI: 2.65-8.93, P = 0.000), diffused lesions (OR = 2.92, 95%CI: 2.03-6.46, P = 0.000), GFR < 60 ml×min(-1)·1.73 m(-2) (OR = 4.73, 95%CI: 3.51-10.62, P = 0.000), smoking (OR = 3.37, 95%CI: 2.39-8.46, P = 0.000), age < 60 years old (OR = 1.44, 95%CI:1.26-4.63, P = 0.024), HbAlc ≥ 6.3% (OR = 2.48, 95%CI: 1.84-4.27, P = 0.002). Risk score was well associated with the rate of ISR in MVC. Sensitivity was 76.5% (95%CI: 64.6%-85.9%), specificity was 76.1% (95%CI: 73.2%-78.7%), and areas under the ROC curve was 0.851(95%CI:0.813-0.890, P = 0.000) when score was set at 5.5. CONCLUSIONS: The incidence of ISR in coronary heart disease patients complicating with diabetes mellitus within 2 years after DES implantation is relatively low. Several factors are associated with ISR in these patients and risk for ISR could be reliably identified by the established scoring model.
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Doença das Coronárias/epidemiologia , Reestenose Coronária/etiologia , Diabetes Mellitus/epidemiologia , Stents Farmacológicos , Idoso , Doença das Coronárias/complicações , Doença das Coronárias/terapia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos RetrospectivosRESUMO
Purpose: Psoriasis is a chronic and recurrent inflammatory dermatitis characterized by T cell imbalance and abnormal keratinocyte proliferation. MicroRNAs (miRNAs) hold promise as therapeutic agents for this disease; however, their clinical application is hindered by poor stability and limited skin penetration. This study demonstrates the utilization of Framework Nucleic Acid (FNA) for the topical delivery of miRNAs in psoriasis treatment. Methods: By utilizing miRNA-125b as the model drug, FNA-miR-125b was synthesized via self-assembly. The successful synthesis and stability of FNA-miR-125b in bovine fetal serum (FBS) were verified through gel electrophoresis. Subsequently, flow cytometry was employed to investigate the cell internalization on HaCaT cells, while qPCR determined the effects of FNA-miR-125b on cellular functions. Additionally, the skin penetration ability of FNA-miR-125b was assessed. Finally, a topical administration study involving FNA-miR-125b cream on imiquimod (IMQ)-induced psoriasis mice was conducted to evaluate its therapeutic efficacy. Results: The FNA-miR-125b exhibited excellent stability, efficient cellular internalization, and potent inhibition of keratinocyte proliferation. In the psoriasis mouse model, FNA-miR-125b effectively penetrated the skin tissue, resulting in reduced epidermal thickness and PASI score, as well as decreased levels of inflammatory cytokines.
Assuntos
MicroRNAs , Psoríase , Animais , Bovinos , Camundongos , MicroRNAs/genética , Queratinócitos , Pele , Psoríase/tratamento farmacológico , Psoríase/induzido quimicamente , Imiquimode/uso terapêutico , Modelos Animais de Doenças , Camundongos Endogâmicos BALB CRESUMO
Chelidonium majus L. contained alkaloids as its main component, exhibiting various biological activities, particularly antibacterial activity. This study aimed to extract alkaloids from C. majus L. (total alkaloids) and evaluate their antibacterial activity both in vitro and in vivo. Reflux extraction was carried out on C. majus L., and the extract was purified with HPD-600 macroporous resin and 732 cation exchange resin columns. Infection modeling of Caenorhabditis elegans (C. elegans) was established to investigate the impact of Methicillin-resistant Staphylococcus aureus (MRSA) and Methicillin-sensitive Staphylococcus aureus (MSSA) on the motility, longevity, and reactive oxygen species (ROS) levels of wild-type worms (N2 strain). The effects of total alkaloids on longevity and ROS were further evaluated in infected N2 worms. Additionally, the effect of total alkaloids on the stress resistance of C. elegans and the mechanism of action were investigated. By utilizing CB1370, DR26 and CF1038 transgenic strains of C. elegans to identify whether the antibacterial activity of total alkaloids was dependent on DAF-2/DAF-16 pathway. The results showed that total alkaloids exhibited a significant antibacterial activity against both MRSA and MSSA (MIC 31.25 µg/mL). Compared with MSSA, the MRSA exhibited a stronger inhibitory effect on the movement behavior and development of worms, along with faster pathogenicity and unique virulence factors. Total alkaloids also displayed the ability to extend the lifespan of C. elegans under oxidative stress and heat stress, and reduce the expression of ROS. The antibacterial activity of total alkaloids was primarily dependent on the DAF-2/DAF-16 pathway, and the presence of functional DAF-2 was deemed essential in total alkaloids mediated immune response against MRSA. Moreover, the antibacterial and anti-infection effects of total alkaloids were found to be associated with the daf-16 gene fragment.
Assuntos
Alcaloides , Antibacterianos , Caenorhabditis elegans , Chelidonium , Staphylococcus aureus Resistente à Meticilina , Caenorhabditis elegans/efeitos dos fármacos , Animais , Alcaloides/farmacologia , Alcaloides/isolamento & purificação , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/isolamento & purificação , Chelidonium/química , Espécies Reativas de Oxigênio/metabolismo , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Longevidade/efeitos dos fármacos , Proteínas de Caenorhabditis elegans , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Staphylococcus aureus/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Chelidonium majusRESUMO
BACKGROUND: The World Health Organization declared mpox an international public health emergency. Since January 1, 2022, China has been ranked among the top 10 countries most affected by the mpox outbreak globally. However, there is a lack of spatial epidemiological studies on mpox, which are crucial for accurately mapping the spatial distribution and clustering of the disease. OBJECTIVE: This study aims to provide geographically accurate visual evidence to determine priority areas for mpox prevention and control. METHODS: Locally confirmed mpox cases were collected between June and November 2023 from 31 provinces of mainland China excluding Taiwan, Macao, and Hong Kong. Spatiotemporal epidemiological analyses, including spatial autocorrelation and regression analyses, were conducted to identify the spatiotemporal characteristics and clustering patterns of mpox attack rate and its spatial relationship with sociodemographic and socioeconomic factors. RESULTS: From June to November 2023, a total of 1610 locally confirmed mpox cases were reported in 30 provinces in mainland China, resulting in an attack rate of 11.40 per 10 million people. Global spatial autocorrelation analysis showed that in July (Moran I=0.0938; P=.08), August (Moran I=0.1276; P=.08), and September (Moran I=0.0934; P=.07), the attack rates of mpox exhibited a clustered pattern and positive spatial autocorrelation. The Getis-Ord Gi* statistics identified hot spots of mpox attack rates in Beijing, Tianjin, Shanghai, Jiangsu, and Hainan. Beijing and Tianjin were consistent hot spots from June to October. No cold spots with low mpox attack rates were detected by the Getis-Ord Gi* statistics. Local Moran I statistics identified a high-high (HH) clustering of mpox attack rates in Guangdong, Beijing, and Tianjin. Guangdong province consistently exhibited HH clustering from June to November, while Beijing and Tianjin were identified as HH clusters from July to September. Low-low clusters were mainly located in Inner Mongolia, Xinjiang, Xizang, Qinghai, and Gansu. Ordinary least squares regression models showed that the cumulative mpox attack rates were significantly and positively associated with the proportion of the urban population (t0.05/2,1=2.4041 P=.02), per capita gross domestic product (t0.05/2,1=2.6955; P=.01), per capita disposable income (t0.05/2,1=2.8303; P=.008), per capita consumption expenditure (PCCE; t0.05/2,1=2.7452; P=.01), and PCCE for health care (t0.05/2,1=2.5924; P=.01). The geographically weighted regression models indicated a positive association and spatial heterogeneity between cumulative mpox attack rates and the proportion of the urban population, per capita gross domestic product, per capita disposable income, and PCCE, with high R2 values in north and northeast China. CONCLUSIONS: Hot spots and HH clustering of mpox attack rates identified by local spatial autocorrelation analysis should be considered key areas for precision prevention and control of mpox. Specifically, Guangdong, Beijing, and Tianjin provinces should be prioritized for mpox prevention and control. These findings provide geographically precise and visualized evidence to assist in identifying key areas for targeted prevention and control.