RESUMO
Chronic neutrophil leukemia (CNL) is a rare and life-threatening disease. Cases of CNL combined with lymphoma are rare. Here, we report a case of CNL with T-acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) in a 28-year-old male. After a regimen of ruxolitinib, VICLP (Vincristine, Idarubicin, Cyclophosphamide, Prednisone, Peg-asparaginase) regimen, high-dose cytarabine, and methotrexate regimens, the patient's bone marrow condition partially resolved. However, when the disease relapsed four months later, despite attempts with selinexor, venetoclax, and CAG(aclarubicin hydrochloride, Algocytidine, Granulocyte Stimulating Factor) chemotherapy, the leukocytes and peripheral blood primitive cells reduced, but the bone marrow did not achieve remission. This pathogenesis may be related to microenvironmental immune escape under prolonged inflammatory stimulation and gene disruption affecting protein function due to colony-stimulating factor 3 receptor gene (CSF3R) mutations. For this type of disease, early intervention may delay disease progression.
RESUMO
BACKGROUND: Although prior studies have demonstrated that children with high levels of fundamental movement skill (FMS) are more active throughout the day, little is known about children's FMS and their physical activity (PA) during different segments of the school day (e.g., recess, lunch break, and physical education). The present study focused on FMS and moderate-to-vigorous PA (MVPA) during school day and identifies the association between children's FMS and MVPA during different segments of the school day in China. METHODS: A total of 322 children (boys n = 163, girls n = 159; Mage = 8.12, SD = 1.22 years) from four elementary schools involved in this study. Children's FMS and MVPA were measured using the Test of Gross Motor Development-2nd edition (TGMD-2) and hip-mounted accelerometers. Data such as height, weight, and socio-economic status (SES) were also obtained. Multilevel mixed regression models were used to examine the cross-sectional associations between FMS and MVPA. Models were adjusted for gender, age, standardized body mass index, and SES. RESULTS: Children engaged in 32.19 min of MVPA during the whole school day. Boys were more active than girls and had higher object-control skills competency. Locomotor skills were positively associated with children's long recess (B = 1.063) and short recess time (B = 1.502) MVPA. Object-control skills were positively correlated with children's MVPA time during long recess (B = 1.244) and physical education (PE) lessons (B = 1.171). CONCLUSION: The findings highlight the importance of developing both locomotor and object-control skills in elementary schools to lead more MVPA engagement during different segments of the school day.
Assuntos
Destreza Motora , Instituições Acadêmicas , Humanos , Feminino , Masculino , Criança , China , Destreza Motora/fisiologia , Estudos Transversais , Exercício Físico , Acelerometria , Atividade Motora/fisiologia , Educação Física e TreinamentoRESUMO
BACKGROUND: Previous research has suggested that engaging in regular physical activity (PA) can help to reduce symptoms of depression and anxiety in university students. However, there is a lack of evidence regarding the impact of reducing sedentary behavior (SB) and increasing light-intensity PA (LPA) on these symptoms. This study aims to address this gap by using isotemporal substitution (IS) models to explore how substituting SB with LPA or moderate-to-vigorous PA (MVPA) affects depression and anxiety symptoms among university students. METHODS: The study recruited 318 university students with a mean age of 21.13 years. Accelerometers were used to objectively measure the time spent on SB, LPA, and MVPA, while depression and anxiety symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D) and the Self-rating Anxiety Scale (SAS). IS models using multivariable linear regression were employed to estimate the associations between different behaviors and depression and anxiety symptoms when 30 min of one behavior was substituted with another. RESULTS: In the single-activity model, less SB (ß = 0.321, 95% CI: 0.089, 1.297) and more MVPA (ß = -0.142, 95% CI: -1.496, - 0.071) were found to be significantly and negatively associated with depression scores, while less SB (ß = 0.343, 95% CI: 0.057, 1.014), LPA (ß = 0.132, 95% CI: 0.049, 1.023), and more MVPA (ß = -0.077, 95% CI: -1.446, - 0.052) were significantly and negatively correlated with anxiety scores. The IS analysis revealed that substituting 30 min of SB with LPA (ß = -0.202, 95% CI: -1.371, - 0.146) or MVPA (ß = -0.308, 95% CI: -0.970, - 0.073) was associated with improvements in depressive symptoms. Substituting 30 min of SB with MVPA (ß = -0.147, 95% CI: -1.863, - 0.034) was associated with reduced anxiety symptoms. CONCLUSION: Replacing 30 min of SB with MVPA may alleviate depression and anxiety symptoms in university students. Further research is needed to explore the long-term effects of PA interventions on the mental health disorders of this population.
Assuntos
Acelerometria , Ansiedade , Depressão , Exercício Físico , Comportamento Sedentário , Estudantes , Humanos , Estudantes/psicologia , Estudantes/estatística & dados numéricos , Masculino , Feminino , Exercício Físico/psicologia , Universidades , Depressão/epidemiologia , Depressão/psicologia , Adulto Jovem , Ansiedade/epidemiologia , China/epidemiologia , AdolescenteRESUMO
Secondary hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease. In the present retrospective study, we aimed to investigate coagulation disorders and their outcome implications in patients with secondary HLH. We evaluated clinical characteristics and the relationship between coagulation indices and prognosis in HLH patients (n = 141). The information, including clinical symptoms, laboratory indicators, and coagulation indices, was evaluated. Coagulation disorders and bleeding events occurred in 95 (67.4%) and 60 (42.6%) patients, respectively. A coagulation index analysis primarily showed elevated levels of D-Dimer, the international standardized ratio (INR), prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT), while the prothrombin activity, fibrinogen levels, and platelet levels were significantly decreased. Dominant disseminated intravascular coagulation (DIC) occurred in 76 patients (53.9%). Patients with lymphoma-associated hemophagocytic syndrome (LAHS) frequently exhibited apparent coagulation disorders. Multivariate analysis revealed that age ≥ 29.5 years, bleeding events, APTT ≥ 47.3 s, fibrinogen ≤ 1.68 g/L, and absolute neutrophil counts (ANC) of ≤ 1.21 × 109/L were independent prognostic factors. We thereby devised a prognostic scoring system and stratified patients into low-risk (0-2 points), intermediate-risk (3-4 points), and high-risk (5-7 points) groups, and the 1-year overall survival rates in the above-mentioned groups were 66.40%, 40.00%, and 2.30%, respectively (P < 0.0001). In conclusion, coagulation dysfunctions and bleeding tendencies were common characteristics in HLH patients. We constructed a novel prognostic score model based on APTT, fibrinogen level, ANC, age, and bleeding events, which had superior prognostic value compared with these markers alone.
RESUMO
Environmental pollutants can disrupt the homeostasis of endogenous metabolites in organisms, leading to metabolic disorders and syndromes. However, it remains highly challenging to efficiently screen for critical biological molecules affected by environmental pollutants. Herein, we found that enzyme could catalyze hydrogen-deuterium (H-D) exchange between a deuterium-labeled environmental pollutant [D38-bis(2-ethylhexyl) phthalate (D38-DEHP)] and several groups of enzyme-regulated metabolites [cardiolipins (CLs), monolysocardiolipins (MLCLs), phospholipids (PLs), and lysophospholipids (LPLs)]. A high-throughput scanning identified the D-labeled endogenous metabolites in a simple enzyme [phospholipase A2 (PLA2)], enzyme mixtures (liver microsomes), and living organisms (zebrafish embryos) exposed to D38-DEHP. Mass fragmentation and structural analyses showed that similar positions were D-labeled in the CLs, MLCLs, PLs, and LPLs, and this labeling was not attributable to natural metabolic transformations of D38-DEHP or incorporation of its D-labeled side chains. Molecular docking and competitive binding analyses revealed that DEHP competed with D-labeled lipids for binding to the active site of PLA2, and this process mediated H-D exchange. Moreover, competitive binding of DEHP against biotransformation enzymes could interfere with catabolic or anabolic lipid metabolism and thereby affect the concentrations of endogenous metabolites. Our findings provide a tool for discovering more molecular targets that complement the known toxic endpoints of metabolic disruptors.
Assuntos
Dietilexilftalato , Poluentes Ambientais , Animais , Dietilexilftalato/metabolismo , Dietilexilftalato/toxicidade , Poluentes Ambientais/toxicidade , Deutério , Hidrogênio , Simulação de Acoplamento Molecular , Medição da Troca de Deutério , Peixe-ZebraRESUMO
Metabolism generally transforms xenobiotics into more polar and hydrophilic products, facilitating their elimination from the body. Recently, a new metabolic pathway that transforms phenolic xenobiotics into more lipophilic and bioactive dimer products was discovered. To elucidate the role of cytochrome P450 (CYP) enzymes in mediating this cross-coupling metabolism, we used high-throughput screening to identify the metabolites generated from the coupling of 20 xenobiotics with four endogenous metabolites in liver microsomes. Endogenous vitamin E (VE) was the most reactive metabolite, as VE reacted with seven phenolic xenobiotics containing various structures (e.g., an imidazoline ring or a diphenol group) to generate novel lipophilic ethers such as bakuchiol-O-VE, phentolamine-O-VE, phenylethyl resorcinol-O-VE, 2-propanol-O-VE, and resveratrol-O-VE. Seven recombinant CYP enzymes were successfully expressed and purified in Escherichia coli. Integration of the results of recombinant human CYP incubation and molecular docking identified the central role of CYP3A4 in the cross-coupling metabolic pathway. Structural analysis revealed the π-π interactions, hydrogen bonds, and hydrophobic interactions between reactive xenobiotics and VE in the malleable active sites of CYP3A4. The consistency between the molecular docking results and the in vitro human cytochrome P450 evaluation shows that docking calculations can be used to screen molecules participating in cross-coupling metabolism. The results of this study provide supporting evidence for the overlooked toxicological effects induced by direct reactions between xenobiotics and endogenous metabolites during metabolic processes.
Assuntos
Citocromo P-450 CYP3A , Xenobióticos , Humanos , Citocromo P-450 CYP3A/metabolismo , Simulação de Acoplamento Molecular , Xenobióticos/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Microssomos Hepáticos/metabolismoRESUMO
Purposes: This cross-sectional study aimed to examine the associations between the 24-h movement behaviours and body mass index (BMI) of students from China by using compositional data analysis. Methods: A total of 389 students aged 6-16 years participated in this study. Accelerometers were used to measure moderate-to-vigorous physical activity (MVPA), light-intensity physical activity (LPA), sedentary behaviour (SED), and sleep. Weight and height were objectively measured. The association between 24-h movement and BMI was analyzed by using compositional data analysis. Results: Time reallocation using minutes and proportions created major differences to the results. Reallocating 10 min from other movement behaviours to MVPA was associated with decreased BMI z-score of 1.372 to 0.158 among primary-school students. Reallocating 10 min from sleep and SED to MVPA, and from sleep and SED to LPA were associated with decreased BMI z-score of 0.505 to 0.017 among middle-school students. Reallocating 10% of time from all other components to SED and sleep were associated with a higher BMI z-score by 0.148 (95%CI: 0.020; 0.276) and 0.125 (95%CI: 0.046; 0.204), while reallocating time to MVPA was associated with a decrease in BMI z-scores of 0.132 (95%CI: -0.193; -0.070) among primary-school students. Reallocating 10% of time from all other components to SED was associated with a higher BMI z-score of 0.254 (95%CI: 0.165; 0.345), whereas reallocating time to MVPA and LPA was associated with a decrease in BMI z-scores of 0.039 (95%CI: -0.073; -0.005) and 0.093 (95%CI: -0.153; -0.033) among middle-school students. Conclusion: Research results of 10-min one-to-one reallocation may be treated cautiously due to uneven distribution of time in 24-h movement behaviours. Based on the results of 10% one-to-remaining reallocation, replacing SED with MVPA may be an appropriate target for adiposity intervention in primary-school students, while increasing MVPA or LPA at the expense of SED may be effective in controlling adiposity of middle-school students in China.
RESUMO
It is generally recognized that phenol-containing molecules mainly undergo phase II metabolic reactions, whereas glucuronide and sulfate are conjugated to form water-soluble products. Here, we report direct reactions of phenolic pollutants (triclosan, alkylphenol, bisphenol A [BPA], and its analogues) and some endogenous metabolites (vitamin E [VE] and estradiol) to generate new lipophilic ether products (e.g., BPA-O-VEs and alkylphenol-O-estradiol). A nontargeted screening strategy was used to identify the products in human liver microsome incubations, and the most abundant products (BPA-O-VEs) were confirmed via in vivo exposure in mice. BPA-O-VEs were frequently detected in sera from the general population at levels comparable to those of glucuronide/sulfate-conjugated BPA. Recombinant human cytochrome P450s were applied to find that CYP3A4 catalyzed the formation of these newly discovered ether metabolites by linking the VE hydroxyl group to the BPA phenolic ring, leading to the significantly reduced antioxidative activities of BPA-O-VEs compared to VEs. The effects of the reaction on the homeostasis of reacted biomolecules were finally assessed by in vitro assay and in vivo mice exposures. The generation of BPA-O-VEs decreased the VE concentrations and increased the reactive oxygen species generation after exposure to BPA at environmentally relevant concentrations. The identified reactions provided an overlooked metabolic disruption pathway for phenolic pollutants.
Assuntos
Poluentes Ambientais , Animais , Compostos Benzidrílicos , Estradiol/metabolismo , Éter , Glucuronídeos , Humanos , Camundongos , SulfatosRESUMO
The transport and storage of ions within solid state structures is a fundamental limitation for fabricate more advanced electrochemical energy storage, memristor, and electrochromic devices. Crystallographic shear structure can be induced in the tungsten bronze structures composed of corner-sharing WO6octahedra by the addition of edge-sharing NbO6octahedra, which might provide more storage sites and more convenient transport channels for external ions such as hydrogen ions and alkali metal ions. Here, we show that Nb2O5·15WO3nanowires (Nb/W = 0.008) with long length-diameter ratio, smooth surface, and uniform diameter have been successfully synthesized by a simple hydrothermal method. The Nb2O5·15WO3nanowires do exhibit more advantages over h-WO3nanowires in electrochemical hydrogen ion storage such as smaller polarization, larger capacity (71 mAh g-1, at 10C, 1C = 100 mA g-1), better cycle performance (remain at 99% of the initial capacity after 200 cycles at 100C) and faster H+ions diffusion kinetics. It might be the crystallographic shear structure induced by Nb doping that does result in the marked improvement in the hydrogen-ion storage performance of WO3. Therefore, complex niobium tungsten oxide nanowires might offer great promise for the next generation of electrochemical energy and information storage devices.
RESUMO
OBJECTIVES: Interleukin-10 (IL-10) has been suggested as a biomarker of disease activity in patients with adult-onset Still's disease (AOSD). In this study, we evaluated the serum IL-10 levels and investigated its clinical relevance in systemic-onset juvenile idiopathic arthritis (SoJIA). METHODS: IL-10 levels were determined in 21 patients diagnosed with SoJIA and 35 patients with fever diseases which were suspected as SoJIA, and IL-10 levels were compared between SoJIA patients with regard to disease activity, disease courses, and other biomarkers. RESULTS: Patients with SoJIA had significantly higher levels of IL-10 compared to patients with other febrile diseases. The serum levels of IL-10 were significantly higher in active SoJIA compared to inactive and positively correlated with known disease activity markers such as erythrocyte sedimentation rate (ESR), C-reactive protein level (CRP), ferritin (FER), and IL-6 levels. Moreover, the levels of IL-10 at diagnosis were significantly higher in SoJIA patients with a nonmonocyclic pattern than in patients with a monocyclic pattern. Compared to CRP, ESR, FER, and IL-6, IL-10 levels were superior in predicting monocyclic patients from nonmonocyclic patients. CONCLUSION: Compared to other febrile diseases, SoJIA patients have markedly higher levels of IL-10 which may assist with diagnosis. And a clear association of serum IL-10 levels with disease activity and disease courses in SoJIA was found. These results suggest that serum IL-10 might be a reliable clinical marker in SoJIA.
Assuntos
Artrite Juvenil , Interleucina-10/sangue , Biomarcadores/sangue , Sedimentação Sanguínea , HumanosRESUMO
BACKGROUND: On the basis of the integration constructs from self-determination theory (SDT) and achievement goal theory (AGT), this study aims to investigate the relationship among classroom motivational climate from four perspectives (i.e. autonomy support, relatedness support, task-involving climate and ego-involving climate), three psychological needs (i.e. autonomy, competence and relatedness), self-determined motivation and physical activity (PA) in secondary physical education (PE). METHODS: Participants consisted of 1186 Chinese students aged 11 to 16 years from three secondary schools in Shanghai. Accelerometers were utilized to measure moderate to vigorous physical activity (MVPA). Questionnaires were used to measure SDT variables (i.e. classroom motivational climate, perceived competence, autonomy, relatedness and self-determined motivation). Structural equation modelling (SEM) was adopted to analyse the hypothesised relationship. RESULTS: SEM analysis revealed that task-involving climate and autonomy support were positively associated with autonomy, relatedness and competence. Relatedness support was positively related with autonomy and relatedness, whereas ego-involving climate was only associated with competence. The three psychological needs positively affected self-determined motivation, and self-determined motivation positively affected the MVPA time of secondary school students in PE lessons. CONCLUSION: These findings support a model of motivation that integrates SDT and AGT, provides new insight into understanding MVPA in Chinese PE, and establishes a solid basis for intervention research.
Assuntos
Motivação , Educação Física e Treinamento , Adolescente , Criança , China , Exercício Físico , Humanos , Autonomia Pessoal , Satisfação Pessoal , Instituições Acadêmicas , EstudantesAssuntos
Imunoconjugados , Linfo-Histiocitose Hemofagocítica , Linfoma Difuso de Grandes Células B , Humanos , Rituximab/efeitos adversos , Cloridrato de Bendamustina/efeitos adversos , Linfo-Histiocitose Hemofagocítica/induzido quimicamente , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/complicações , Anticorpos Monoclonais/uso terapêutico , Imunoconjugados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Linfoma Difuso de Grandes Células B/tratamento farmacológicoRESUMO
PURPOSE OF THE STUDY: Genome-wide association studies have revealed an association of ADAMTS7 polymorphisms with the risk of cardiovascular diseases. Nonetheless, the role of ADAMTS7 polymorphisms on myocardial infarction (MI) risk remains poorly understood. Here, we aim to evaluate the effect of ADAMTS7 tag single nucleotide polymorphisms (SNPs) on individual susceptibility to MI. STUDY DESIGN: Genotyping of the four tagSNPs (rs1994016, rs3825807, rs4380028 and rs7173743) was performed in 232 MI cases and 661 control subjects using PCR-ligase detection reaction (LDR) method. The association of these four tagSNPs with MI risk was performed with SPSS software. RESULTS: Multivariate logistic regression analysis showed that ADAMTS7 tagSNP rs3825807 exhibited a significant effect on MI risk. Compared with the TT homozygotes, the CT genotype (OR1.93, 95% CI1.30to 2.85, Pc=0.004) and the combined CC/CT genotypes (OR1.70, 95% CI1.16 to 2.50, Pc=0.028) were statistically significantly associated with the increased risk for MI. Further stratified analysis revealed a more significant association with MI risk among older subjects, hypertensives, non-diabetics and patients with hyperlipidaemia. Consistently, the haplotype rs1994016T-rs3825807C containing rs3825807 C allele exhibited increased MI risk (OR1.52, 95% CI1.10 to 2.10, p=0.010). However, we did not detect any association of the other three tagSNPs with MI risk. CONCLUSIONS: Our finding suggest that ADAMTS7 tagSNP rs3825807 contributes to MI susceptibility in the Chinese Han population. Further studies are necessary to conï¬rm the general validity of our ï¬ndings and to clarify the underlying mechanism for this association.
Assuntos
Proteína ADAMTS7/genética , Infarto do Miocárdio/genética , Estudos de Casos e Controles , China/etnologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etnologia , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
Estrone molecularly imprinted polymers were synthesized through the self-polymerization of dopamine on the surface of silica gels, which had the characteristics of mild polymerization conditions, simple reaction procedure and good specific recognition ability for estrone. The estrone molecularly imprinted polymers were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, elemental analysis and nitrogen adsorption-desorption tests. The characterization confirmed that the imprinted polymers were successfully grafted on the surface of silica gels. Through investigating the adsorption performance, the prepared estrone molecularly imprinted polymers exhibited high adsorption capacity, fast mass transfer, as well as excellent selectivity toward estrone. The estrone molecularly imprinted polymers as the solid-phase extraction adsorbent coupled with high-performance liquid chromatography was developed to determine estrone from the milk samples. The developed estrone molecularly imprinted polymer solid-phase extraction with high-performance liquid chromatography method exhibited satisfactory specificity, precision, accuracy and good linearity relationship in the range of 0.2-20 µg/mL. The developed method is simple, fast, effective and high specificity method and it provides a new method to detect the residues of estrone in animal foods.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Estrona/análise , Estrona/isolamento & purificação , Leite/química , Polímeros/química , Extração em Fase Sólida/métodos , Adsorção , Animais , Bovinos , Indóis/química , Impressão Molecular , Polímeros/síntese química , Dióxido de Silício/química , Extração em Fase Sólida/instrumentaçãoRESUMO
An effective and simple method was established for the separation and enrichment of steroidal saponins from Trillium tschonoskii Maxim. The adsorption and desorption properties of seven macroporous resins were investigated. Among the tested resins, AB-8 resin showed the best adsorption and desorption capacities. The adsorption of steroidal saponins on AB-8 at 25°C was quite consistent with both the Freundlich isotherm model and the pseudo-second-order kinetics model. By optimizing the dynamic adsorption and desorption parameters, the content of steroidal saponins increased from 5.20% in the crude extracts to 51.93% in the final product, with a recovery yield of 86.67%. Furthermore, by scale-up separation, the concentration and recovery of total steroidal saponins were 43.8 and 85.5%, respectively, which suggested that AB-8 resin had great industrial and pharmaceutical potential because of its high efficiency and cost-effectiveness. In addition, a high-performance liquid chromatography method for the simultaneous determination of eight steroidal saponins was established for the first time, which was employed to qualitatively and quantitatively analyze the final product. Based on the methodological validation results, the high-performance liquid chromatography method can be widely applied to the quality control of steroidal saponins from Trillium tschonoskii Maxim due to its excellent accuracy, stability, and repeatability.
Assuntos
Extratos Vegetais/química , Resinas Sintéticas , Saponinas/isolamento & purificação , Trillium/química , Adsorção , Cromatografia Líquida de Alta PressãoRESUMO
In this study, the chemical composition and antioxidant and anti-inflammatory activities of sweet basil (Ocimum basilicum L. Lamiaceae family) were evaluated. Sweet basil is a food-related plant that is widely used in traditional Chinese medicine. Sweet basil crude oil was processed via molecular distillation and further characterized using gas chromatography-mass spectrometry (GC-MS) to screen for new compounds. The GC-MS analysis identified thirty-eight compounds. The major constituents of the residue fraction were estragole (17.06%), methyl eugenol (11.35%) and linoleic acid (11.40%), while the distillate fraction primarily contained methyl eugenol (16.96%), α-cadinol (16.24%) and α-bergamotene (11.92%). The antioxidant (DPPH and ABTS assays) and anti-inflammatory (in Raw264.7 cells) activities were evaluated. The residue fraction markedly scavenged the DPPH (IC50 = 1.092 ± 0.066 mg/mL) and ABTS (IC50 = 0.707 ± 0.042 mg/mL) radicals. Meanwhile, the distillate fraction distinctly suppressed the production of cytokines (TNF-α, IL-ß, IL-6) and their gene expression in LPS-induced Raw264.7 cells and suppressed NO and iNOS in an in vitro model when compared with the crude oil. In conclusion, the fractions obtained from sweet basil crude oil showed different antioxidant and anti-inflammatory properties, and they could be used as an effective source of natural antioxidant and anti-inflammatory agents after molecular distillation. Thus, the properties of essential oils in natural herbal medicines may be maximized to provide a valuable therapeutic strategy for treating various disorders caused by extreme oxidative stress.
RESUMO
The use of cheaper and recyclable biomaterials (like eggshells) to synthesize high purity hydroxyapatite (HAp) with better properties (small particle size, large surface area and pore volume) for applications (in environmental remediation, bone augmentation and replacement, and drug delivery systems) is vital since high-purity synthetic calcium sources are expensive. In this work, pure and mesoporous HAp nanopowder with large pore volume (1.4 cm3/g) and surface area (284.1 m2/g) was produced from raw eggshells at room temperature using a simple two-step procedure. The control of precursor droplets could stabilize the pH value of the reaction solution, because of the size of the needle (of the syringe pump used for precursor additions) leading to production of HAp with high surface area and pore size. The as-produced HAp revealed high ibuprofen (as a model drug) loading (1.38 g/g HAp), enhanced dissolution and controllable release of the drug via solute-saturated supercritical carbon dioxide.
Assuntos
Dióxido de Carbono/química , Durapatita/química , Ibuprofeno/química , Preparações Farmacêuticas/química , Animais , Materiais Biocompatíveis/química , Sistemas de Liberação de Medicamentos/métodos , Concentração de Íons de Hidrogênio , Tamanho da Partícula , Poríferos/química , Porosidade , Solubilidade , TemperaturaRESUMO
Varicocele (VC) is a common cause of infertility in men. Pathophysiological changes caused by VC, such as testicular hypoxia, high temperatures, oxidative stress, abnormal reproductive hormones, and Cd accumulation, can induce autophagy, thus affecting the reproductive function in patients with this condition. Autophagy regulators can be classified as activators or inhibitors. Autophagy activators upregulate autophagy, reduce the damage to the testis and epididymis, inhibit spermatogenic cell apoptosis, and protect fertility. In contrast, autophagy inhibitors block autophagy and aggravate the damage to the reproductive functions. Therefore, elucidating the role of autophagy in the occurrence, development, and regulation of VC may provide additional therapeutic options for men with infertility and VC. In this review, we briefly describe the progress made in autophagy research in the context of VC.
Assuntos
Autofagia , Varicocele , Autofagia/fisiologia , Varicocele/complicações , Masculino , Humanos , Animais , Infertilidade Masculina/etiologia , TestículoRESUMO
Background: Hemophagocytic lymphohistiocytosis (HLH) patients who need intensive care usually have multiple organ failure and poor prognosis. However, the clinical characteristics, therapeutic efficacy and outcome in these critically ill HLH patients have remained unclear. Methods: We performed a retrospective study of 50 critically ill HLH patients from September 2013 to October 2022. Patients' information was collected, and the overall survival rate was estimated. Results: Fifty HLH patients need intensive care, and the median sequential organ failure assessment (SOFA) score was 8. 66.00% patients had septic shock, 60.00% had disseminated intravascular coagulation (DIC) and 56.00% had acute respiratory distress syndrome (ARDS). 64.00% patients needed vasoactive drugs, 60.00% needed invasive or non-invasive positive pressure mechanical ventilation, and 12.00% needed continuous renal replacement therapy (CRRT). Among 18 patients received the etoposide-based regimens, the median time for 17 patients to remove ECG monitoring was 13 days (4-30 days); the median time to remove respiratory support in 10 patients was 8.5 days (4-21 days); the median time for 5 patient to convert from dominant DIC to non-dominant DIC was 4 days (1-14 days) and the median time for 6 patients to stop using vasoactive drugs was 10 days (2-14 days). After 4 weeks of treatment, 7 patients were evaluated as NR, 6 achieved PR, and 5 could not be evaluated. The ORR was 55.56%. Up to the last follow-up, the OS rate of patients receiving etoposide-based regimens was 66.67%. In contrast, all 32 HLH patients in other groups died. Univariate analysis showed that PCT > 0.5 ug/L, PT prolonged > 6 s, TBil > 25umol/L, respiratory failure, renal failure, liver failure and did not receive etoposide- based regimens were the negative factors affecting survival (P = 0.001, 0.017, 0.043, 0.001, 0.000, 0.029, 0.000). Conclusion: HLH patients who need intensive care timely used etoposide-based HLH regimens might rescue critically ill patients successfully.
RESUMO
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory clinical syndrome of uncontrolled immune response which results in hypercytokinemia due to underlying primary or secondary immune defect. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only cure therapy for primary HLH and recurrent/refractory hemophagocytic lymphohistiocytosis. Compared with children HLH, adult HLH is a much more heterogeneous syndrome requiring a more individualized protocol depending on the underlying trigger, disease severity and genetic background. At present, there remain controversies in various aspects including indications of haematopoietic cell transplantation (HCT), conditioning regimen, efficacy and prognosis. This article will review the recent advances of allo-HSCT in the treatment of adult HLH based on the above issues.