RESUMEN
Proteolysis-targeting chimera (PROTAC) has become a very important means of protein degradation and a new way of disease treatment. In particular, PROTACs constructed with ligands for E3 ligase cereblon account for more than 90 % of the PROTACs currently in clinical research. Notably, CRBN ligands themselves are a class of molecular glue compounds capable of degrading neo-substrate proteins. Compared to the target proteins degradation, the degradation of neo-substrates, especially IKZF2, has not received enough attention. Therefore, this review summarizes the currently published IKZF2 degraders derived from articles and patents, which are conducive to the design of PROTACs with desired IKZF2 degradation from the perspective of medicinal chemistry.
Asunto(s)
Proteolisis , Ubiquitina-Proteína Ligasas , Ubiquitina-Proteína Ligasas/metabolismo , Proteolisis/efectos de los fármacos , Humanos , Diseño de Fármacos , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Ligandos , Factor de Transcripción Ikaros/metabolismo , Quimera Dirigida a la ProteólisisRESUMEN
BACKGROUND: Neurospecific Enolase (NSE), a multifunctional protein, is present in various tissues of the body and plays an important role in many disease processes, such as infection, inflammation, tumours, injury, and immunity. In recent years, the application of NSE in respiratory diseases has become increasingly widespread and a research hotspot. OBJECTIVE: This study aims to explore the relationship between NSE and childhood pneumonia, providing assistance for the diagnosis and assessment of pneumonia. METHODS: Using prospective research and case-control methods, We selected 129 children with pneumonia hospitalised in Weifang People's Hospital from September 2020 to April 2022 as the case group. Among them were 67 cases of Mycoplasma pneumoniae pneumonia (MP+), 62 cases of non-Mycoplasma pneumoniae pneumonia (MP -), and 21 cases of severe pneumonia. At the same time, 136 children who underwent outpatient health examinations were selected as the control group. The levels of NSE, ESR, CRP in cases group and NSE in control group were measured separately. RESULT: The NSE levels in the MP + group were 17.86 (14.29-22.54) ng/mL, while those in the MP- group were 17.89 (14.10-21.66) ng/mL, both of which were higher than the control group's NSE levels of 13.26(12.18,14.44) ng/mL (H = 46.92, P = 0.000). There was no statistically significant difference in NSE levels between the MP + and MP - groups (P > 0.05). The NSE level in the severe pneumonia group was 27.38 (13.95-34.06) ng/mL, higher than that in the mild pneumonia group, which was 17.68 (14.27-21.04) ng/mL, (P = 0.024). The AUC values for diagnosing pneumonia are NSE0.714, CRP0.539, and ESR0.535, with NSE having the highest diagnostic value. CONCLUSION: Serum NSE can serve as an inflammatory indicator for paediatric pneumonia, which has important clinical guidance significance for the diagnosis, condition evaluation, and prognosis of paediatric pneumonia.
Asunto(s)
Biomarcadores , Fosfopiruvato Hidratasa , Neumonía por Mycoplasma , Neumonía , Humanos , Fosfopiruvato Hidratasa/sangre , Estudios de Casos y Controles , Femenino , Masculino , Preescolar , Niño , Estudios Prospectivos , Neumonía por Mycoplasma/sangre , Neumonía por Mycoplasma/diagnóstico , Neumonía/sangre , Neumonía/diagnóstico , Biomarcadores/sangre , Lactante , Proteína C-Reactiva/análisis , Relevancia ClínicaRESUMEN
Limb expression 1-like protein (LIX1L) might be an RNA-binding protein involved in post-transcriptional regulation. However, little is known regarding the biological function and mechanism of LIX1L in cancer cells. Here we demonstrate a clear correlation between LIX1L expression and epithelial-mesenchymal transition (EMT) markers in 81 non-small cell lung cancer (NSCLC) tissues and The Cancer Genome Atlas database, suggesting that LIX1L is a mesenchymal marker. Besides, LIX1L expression is obviously elevated in TGFß1-induced EMT NSCLC cells and enhances cell migration, invasion, anoikis resistance, epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance, and proliferation. Interestingly, the increased LIX1L expression prominently localizes to the nucleoli, where it physically interacts with the key ribosome biogenesis regulator NCL protein, inducing ribosomal RNA (rRNA) synthesis in EMT NSCLC cells. NCL knockdown or inhibition of rRNA synthesis reverses the enhanced EMT functions and proliferation ability caused by LIX1L overexpression in NSCLC cells, indicating that NCL expression and rRNA synthesis participates in LIX1L-mediated biological functions during EMT. Collectively, our findings suggest that the LIX1L-NCL-rRNA synthesis axis is a novel EMT-activated mechanism. Targeting the pathway might be a therapeutic option for EMT and EGFR-TKI resistance in NSCLC.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Línea Celular Tumoral , Resistencia a Antineoplásicos , Transición Epitelial-Mesenquimal/genética , Receptores ErbB , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Ribosomas/metabolismo , ARN Ribosómico/genética , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Proteínas Relacionadas con la Autofagia/metabolismo , NucleolinaRESUMEN
INTRODUCTION: Current research on the posterior urethral valve (PUV) mainly focuses on the follow-up of bladder function after valve ablation. However, few studies exist on the changes in bladder function before and after valve ablation. OBJECTIVES: To investigate the urodynamic changes before and after PUV ablation and determine the effect of operation on bladder function, in patients. MATERIALS AND METHODS: The clinical records of 38 boys diagnosed with PUV and undergone urodynamic exams before and after valve ablation were retrospectively reviewed. In addition, differences in patients' radiographic studies and urodynamic characteristics between pre- and post-operation were evaluated. Moreover, the urodynamic data was compared using the paired t-test and all the data was expressed as means ± SEM. Additionally, p values less than 0.05 were considered to be statistically significant. RESULTS: All the patients were diagnosed with PUV and the follow-up period after operation ranged between 9 and 114 months. The urodynamic exams were performed about 6 months after operation. The results revealed that bladder compliance improved from 8.49 ± 4.73 to 13.31 ± 6.78 ml/cmH2O while the maximum detrusor pressure decreased from 95.18 ± 37.59 to 50.71 ± 21.71 cmH2O, after valve ablation. Additionally, there were significant differences in the pre- and post-operation values of bladder compliance and maximum detrusor pressure (p < 0.05). However, there were no significant differences in the pre- and post-operation values with regard to the residual urine volume, maximum bladder volume and maximum urinary flow rate (p > 0.05). CONCLUSIONS: The adequacy of the COPUM incision is necessary. But the study showed that endoscopic valve ablation couldn't by itself completely improve the bladder function of patients diagnosed with PUV. However, it was able to improve bladder compliance and decrease maximum detrusor pressure to a certain extent. However, bladder compliance still couldn't reach the normal level.
Asunto(s)
Fallo Renal Crónico , Insuficiencia Renal Crónica , Obstrucción Uretral , Masculino , Humanos , Uretra/cirugía , Urodinámica , Estudios Retrospectivos , Obstrucción Uretral/cirugíaRESUMEN
Radix Astragali (RA) is an important Traditional Chinese Medicine widely used in the treatment of various diseases, such as pneumonia, atherosclerosis, diabetes, kidney and liver fibrosis. The role of isoflavonoids from RA in the treatment of liver injury remains unclear. The study aimed to explore hepatoprotective and anti-inflammatory effects of isoflavonoids from Astragalus mongholicus. Network pharmacological analysis showed that RA had a multi-target regulating effect on alleviating liver injury and inhibiting inflammation through its active ingredients, among which isoflavones were closely related to its key molecular targets. The anti-inflammatory and liver protection effects of isoflavonoids of RA were investigated using lipopolysaccharide (LPS)-induced RAW 264.7 cells in vitro and LPS/D-galactosamine (D-gal)-induced acute liver injury mice in vivo. The experimental results showed that methylnissolin (ML) and methylnissolin-3-O-ß-D-glucoside (MLG) presented more notable anti-inflammatory effects. Both of them suppressed the release of pro-inflammatory cytokines, such as iNOS, COX-2, IL-1ß, IL-6, and TNF-α in LPS-stimulated RAW 264.7 cells. In vivo investigation demonstrated that ML markedly meliorated liver injury in LPS/D-gal-induced mice. Western blot results revealed that ML and MLG down-regulated the expression of proinflammatory cytokines via NF-κB signaling pathway. The isoflavonoids, methylnissolin (ML), and methylnissolin-3-O-ß-D-glucoside (MLG), play a vital role in the hepatoprotective and anti-inflammatory effects of RA.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Flavonas , Ratones , Animales , Lipopolisacáridos/farmacología , Galactosamina/metabolismo , Galactosamina/farmacología , Hígado , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antiinflamatorios/metabolismo , Citocinas/metabolismo , FN-kappa B/metabolismo , Flavonas/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismoRESUMEN
BACKGROUND: To develop a fully automated CNN detection system based on magnetic resonance imaging (MRI) for ACL injury, and to explore the feasibility of CNN for ACL injury detection on MRI images. METHODS: Including 313 patients aged 16 - 65 years old, the raw data are 368 pieces with injured ACL and 100 pieces with intact ACL. By adding flipping, rotation, scaling and other methods to expand the data, the final data set is 630 pieces including 355 pieces of injured ACL and 275 pieces of intact ACL. Using the proposed CNN model with two attention mechanism modules, data sets are trained and tested with fivefold cross-validation. RESULTS: The performance is evaluated using accuracy, precision, sensitivity, specificity and F1 score of our proposed CNN model, with results of 0.8063, 0.7741, 0.9268, 0.6509 and 0.8436. The average accuracy in the fivefold cross-validation is 0.8064. For our model, the average area under curves (AUC) for detecting injured ACL has results of 0.8886. CONCLUSION: We propose an effective and automatic CNN model to detect ACL injury from MRI of human knees. This model can effectively help clinicians diagnose ACL injury, improving diagnostic efficiency and reducing misdiagnosis and missed diagnosis.
Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Lesiones del Ligamento Cruzado Anterior/diagnóstico por imagen , Área Bajo la Curva , Redes Neurales de la Computación , Proyectos de InvestigaciónRESUMEN
Wilms tumor (WT) is the second most common solid tumor in pediatric population. Botryoid WT is an uncommon growth pattern of WT, which is characterized by tumor extension into collecting system. A case of a 27-month-old boy with botryoid WT and left-sided inferior vena cava is reported in this article to emphasize the importance of preoperative imaging in preoperative planning.
Asunto(s)
Neoplasias Renales , Malformaciones Vasculares , Tumor de Wilms , Masculino , Humanos , Niño , Preescolar , Vena Cava Inferior/diagnóstico por imagen , Vena Cava Inferior/cirugía , Vena Cava Inferior/patología , Tumor de Wilms/diagnóstico por imagen , Tumor de Wilms/cirugía , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/cirugía , Neoplasias Renales/patologíaRESUMEN
BACKGROUND: At present, there is no specific research on the factors affecting the success rate of urethroplasty in patients with DSD. The purpose of this study is to explore the factors affecting the success of urethroplasty in DSD patients, and to provide some reference for the surgical treatment of DSD patients undergoing urethroplasty. METHOD: We reviewed patients with DSD who underwent urethroplasty from January 2016 to December 2019 retrospectively. Patients were divided into four groups: the successful group, the urethrocutaneous fistula group, the urethral diverticulum group, and the urethral stricture group. Risk factors were determined from the following data included the DSD classification, the age of first operation, length of urethral defect, degree of hypospadias, cryptorchidism, micropenis, gonad type, hormone therapy before operation, transposition of penis and scrotum, surgical strategy, urethral covering material, and postoperative catheter removal time. We explored the difference of each factor between four groups through the comparative study of single factor and multifactor logistic regression analysis of related factors. RESULT: 122 cases were enrolled in this group (n = 122), 12 cases were lost to follow-up. Median follow-up was 28 months (12-55 months).We found the success rate of operation decreased with longer urethral defect (B = - 0.473, P = 0.005). The success rate of operation was higher in staged operation and TPIT (TPIT = Transverse Preputial Island Tube operation)-related operation than primary operation (B = 1.238, P = 0.006) and TPIT-nonrelated operation (B = 2.293, P = 0.001). Although there was a significant difference between the age of the first operation and the occurrence of urethrocutaneous fistula (P = 0.006 < 0.05), there was no significant difference in logistic regression analysis (P = 0.161 > 0.05). The incidence of urethrocutaneous fistula was lower in TPIT-related operation than in TPIT-nonrelated operation (B = - 2.507, P = 0.000). The incidence of postoperative urethral diverticulum was lower in staged operation than in primary operation (B = - 1.737, P = 0.015). CONCLUSION: For patients with disorder of sex development undergoing urethroplasty, the length of urethral defect is an independent risk factor affecting both the success rate of operation and the urethrocutaneous fistula. The age of the first operation has a statistically significant effect on the occurrence of postoperative urethrocutaneous fistula, but it is not an independent factor. Urethrocutaneous fistula is less found in TPIT-related operation in the study. Staged operation is an independent protective factor for postoperative urethral diverticulum compared with one-stage operation but isn't related to urethrocutaneous fistula.
Asunto(s)
Divertículo , Hipospadias , Estrechez Uretral , Divertículo/cirugía , Humanos , Hipospadias/etiología , Hipospadias/cirugía , Masculino , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Uretra/cirugía , Estrechez Uretral/cirugía , Procedimientos Quirúrgicos Urológicos Masculinos/efectos adversosRESUMEN
Riligustilide (RG), one of the dimeric phthalides of Angelica sinensis and Ligusticum chuanxiong, was confirmed effective against many diseases. However, its effects on type 2 diabetes mellitus (T2DM) and the underlying molecular mechanisms have not been clearly elucidated yet. The current study was designed to investigate the hypoglycemic potential by which RG affects the pathogenesis of T2DM. Comprehensive insights into the effects and underlying molecular mechanisms of RG on attenuating aberrant metabolism of glucose were determined in high-fat diet-induced T2DM mice and insulin-resistant (IR) HepG2 cells. In high-fat diet-induced C57BL/6J mice, RG administration significantly reduced hyperglycemia, decreased hyperinsulinemia, and ameliorated glucose intolerance. Mechanistically, RG activated PPARγ and insulin signaling pathway to improve insulin sensitivity, and increase glucose uptake as well as glycogenesis. In addition, RG also upregulated AMPK-TORC2-FoxO1 axis to attenuate gluconeogenesis in vivo and in vitro. According to the findings, RG may be a promising candidate for the treatment of T2DM.
Asunto(s)
Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Animales , Benzofuranos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Gluconeogénesis , Ratones , Ratones Endogámicos C57BLRESUMEN
Coronavirus Disease 2019 (COVID-19) still presents a pandemic trend globally. Detecting infected individuals and analyzing their status can provide patients with proper healthcare while protecting the normal population. Chest CT (computed tomography) is an effective tool for screening of COVID-19. It displays detailed pathology-related information. To achieve automated COVID-19 diagnosis and lung CT image segmentation, convolutional neural networks (CNNs) have become mainstream methods. However, most of the previous works consider automated diagnosis and image segmentation as two independent tasks, in which some focus on lung fields segmentation and the others focus on single-lesion segmentation. Moreover, lack of clinical explainability is a common problem for CNN-based methods. In such context, we develop a multi-task learning framework in which the diagnosis of COVID-19 and multi-lesion recognition (segmentation of CT images) are achieved simultaneously. The core of the proposed framework is an explainable multi-instance multi-task network. The network learns task-related features adaptively with learnable weights, and gives explicable diagnosis results by suggesting local CT images with lesions as additional evidence. Then, severity assessment of COVID-19 and lesion quantification are performed to analyze patient status. Extensive experimental results on real-world datasets show that the proposed framework outperforms all the compared approaches for COVID-19 diagnosis and multi-lesion segmentation.
RESUMEN
A carrier gas mixture of nitrogen and helium has been employed to improve the resolving power at the expense of sensitivity for planar high-field asymmetric ion mobility spectrometry (FAIMS) in previous work. In this paper, a new hollow needle-to-ring ion source was developed, where the helium and nitrogen enter from the hollow needle and ring, respectively. It was found that the signal strengths of acetone, ethanol, and ethyl acetate increased by 8.5, 2.0, and 3.3 times for helium ratios of 20%, 20%, and 10%, respectively. At the same time, the absolute value of compensation voltage and the number of ion peaks increases. It shows that adding an appropriate helium ratio to nitrogen simultaneously improved the sensitivity and resolving power of planar FAIMS, which is reported for the first time.
RESUMEN
Twenty seven dihydro-ß-agarofuran sesquiterpenoids, including fifteen new congeners, wilforsinines I-W (1-9, 12-13, 24-27), and twelve known compounds were isolated from the dried root of Tripterygium wilfordii. The structures of the new sesquiterpenoids, wilforsinines I-W, were elucidated by extensive spectroscopic data analysis. The anti-inflammatory activity of isolates 1-27 were evaluated by examining their inhibitory effects on nitric oxide (NO) production in LPS-induced RAW 264.7 macrophage cells. Among them, wilforsinine K (3) and angulatin M (16) exerted optimal inhibitory effects on the production of NO in LPS-induced RAW 264.7 cells. Moreover, Western blot results revealed that their anti-inflammatory activities were correlated with the suppression of the expression of nitric oxide synthase (iNOS) and down-regulation of the level of NF-κB p65 phosphorylation.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Inflamación/tratamiento farmacológico , Sesquiterpenos/farmacología , Tripterygium/química , Animales , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Inflamación/metabolismo , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Ratones , Estructura Molecular , FN-kappa B/antagonistas & inhibidores , FN-kappa B/metabolismo , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa/metabolismo , Fosforilación/efectos de los fármacos , Células RAW 264.7 , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificación , Relación Estructura-ActividadRESUMEN
ETS variant 4 (ETV4), together with ETV1 and ETV5, constitute the PEA3 subfamily of ETS transcription factors, which are implicated in the progression of many cancers. However, the clinicopathologic significance and molecular events regulated by ETV4 in lung cancer are still poorly understood, especially in squamous cell carcinoma of the lung. Here, we aimed to identify functional targets involved in ETV4-driven lung tumorigenesis. Microarray analysis and validation data revealed that ETV4 was the most preponderant PEA3 factor, which was significantly related to the advanced stage, lymph node metastasis, and poor prognosis of non-small cell lung cancers (NSCLCs; all P < .001). Reduced ETV4 expression suppressed the growth and metastasis of NSCLC both in vivo and in vitro. Microarray, gain, or loss of function and luciferase report assays revealed the direct regulatory effect of ETV4 on the expression of focal adhesion gene PXN and matrix metalloproteinase 1 (MMP1), and PXN and/or MMP1 inhibition partially abolished cell proliferation and migration induced by ETV4. Kaplan-Meier analysis indicated that ETV4 and PXN or MMP1 co-overexpression is associated with poor prognosis in human NSCLCs. In conclusion, the ETV4-PXN and ETV4-MMP1 axes are useful biomarkers of tumor progression and worse outcomes in NSCLCs.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/genética , Metaloproteinasa 1 de la Matriz/genética , Paxillin/genética , Proteínas Proto-Oncogénicas c-ets/genética , Animales , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Progresión de la Enfermedad , Femenino , Humanos , Neoplasias Pulmonares/patología , Ratones Endogámicos BALB C , Ratones Desnudos , Activación TranscripcionalRESUMEN
USP7 has been regarded as a potential therapeutic target for cancer. In this study, virtual screening, molecular dynamics (MD) simulation, and biological evaluation have been applied for the discovery of novel USP7 inhibitors targeting the catalytic active site. Among the obtained compounds, compound 12 with a novel scaffold structure exhibited certain USP7 inhibitory activity (Ub-AMC assay IC50 = 18.40 ± 1.75 µM, Ub-Rho assay IC50 = 7.75 µM). The binding affinity between USP7CD (USP7 catalytic domain) and this hit compound was confirmed with a KD value of 4.46 ± 0.86 µM. Preliminary in vitro studies disclosed its antiproliferative activity on human prostate cancer cell line LNCaP with an IC50 value of 15.43 ± 3.49 µM. MD simulation revealed the detailed differences of protein-ligand interactions between USP7CD and the ligands, including the reference compound ALM4 and compound 12, providing some important information for improving the bioactivity of 12. This hit compound will serve as a promising starting point for facilitating the further discovery of novel USP7 inhibitors.
Asunto(s)
Simulación de Dinámica Molecular , Neoplasias , Dominio Catalítico , Humanos , Simulación del Acoplamiento Molecular , Peptidasa Específica de Ubiquitina 7/metabolismoRESUMEN
N-Alkylated 4-pyridones were obtained through a one-pot procedure involving either normal or interrupted Pummerer reactions between triflic anhydride-activated sulfoxides and 4-fluoropyridine derivatives, followed by hydrolysis. On the other hand, triflic anhydride-activated benzyl 6-fluoro-2-pyridyl sulfoxide could react with alkenes or alkynes to afford thiazolo[3,2-a]pyridin-5-ones, via the pyridinium salt intermediates.
RESUMEN
BACKGROUND The aim of this study was to explore the expression levels of micro ribonucleic acid-10b (miR-10b) and micro ribonucleic acid-181b (miR-181b) in gastric cancer tissues, as well as their application value in clinical diagnosis and treatment. MATERIAL AND METHODS A total of 120 patients with gastric cancer who were diagnosed and treated in the Department of Gastroenterology of our hospital were enrolled in this study. The gastric cancer tissues and paracancerous tissues were collected for measuring the expression of miR-10b and miR-181b by in situ hybridization and reverse transcription-polymerase chain reaction (RT-PCR). The 5-year survival rate was also analyzed. RESULTS The expressions of miR-10b and miR-181b in gastric cancer tissues were both upregulated and were significantly higher than those in the paracancerous tissues (p<0.05). In addition, the expressions of miR-10b and miR-181b in gastric cancer tissues were correlated with tumor size, degree of pathological differentiation, depth of infiltration, tumor node metastasis (TNM) staging, and lymph node metastasis, as well as local lymph node and distant metastasis (p<0.05). For patients in stage II and III, the expressions of miR-10b and miR-181b were significantly correlated with the 5-year survival rate. CONCLUSIONS The high expressions of miR-10b and miR-181b are significantly correlated with poor prognosis in stage II and III patients with gastric cancer, suggesting that their expressions might be criteria for evaluating the prognosis of gastric cancer.
Asunto(s)
MicroARNs/genética , Neoplasias Gástricas/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , MicroARNs/biosíntesis , MicroARNs/metabolismo , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Análisis de Supervivencia , Tasa de Supervivencia , TranscriptomaRESUMEN
OBJECTIVE: To explore the efficacy and safety of recombinant human thrombopoietin (rhTPO) combined with high-dose dexamethasone (DXM) in the treatment of children with refractory immune thrombocytopenic purpura (ITP). METHODS: Fifty-eight ITP children who had failed first-line therapy were randomly divided into two groups: DXM treatment (n=27) and rhTPO + DXM treatment (n=31). The DXM treatment group received two continuous cycles of DXM treatment; in each cycle, patients received high-dose DXM (0.6â mg/kg daily) by intravenous drip for 4 days every 28 days. The rhTPO group received subcutaneous injection of rhTPO (300â U/kg daily) for 14 days additional to DXM treatment. The overall response rate (marked response rate + slight response rate) and adverse reactions were evaluated after 3, 7, and 14 days and 1, 2, and 3 months of treatment. RESULTS: After 7 and 14 days and 1 month of treatment, the rhTPO + DXM treatment group had a significantly higher marked response rate and a significantly higher overall response rate than the DXM treatment group (P<0.05). After 2 months of treatment, the rhTPO + DXM treatment group had a significantly higher overall response rate than the DXM group (P<0.05). One patient in the DXM treatment group had liver damage during the first week of treatment. There was no hypertension, fever, rash, allergy, or weakness in the two groups. CONCLUSIONS: rhTPO combined with high-dose DXM is an effective and safe approach for treating refractory ITP.
Asunto(s)
Dexametasona/administración & dosificación , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Trombopoyetina/administración & dosificación , Niño , Preescolar , Dexametasona/efectos adversos , Quimioterapia Combinada , Femenino , Humanos , Lactante , Masculino , Proteínas Recombinantes/administración & dosificación , Trombopoyetina/efectos adversos , Resultado del TratamientoRESUMEN
Expeditious access to oxadiazepines via 1,5-hydride shift/cyclization of pyrrolidine- or tetrahydroisoquinoline-containing nitrones has been developed. With 1,3-dipole nitrones serving as the hydride acceptors, this transformation was promoted by a Lewis acid, providing access to structurally diverse oxadiazepines in good yields. A one-pot process for in situ nitrone formation, a 1,5-hydride shift, and ring cyclization was also realized.
RESUMEN
Crushing waste concrete and using it directly as RAs has the disadvantages of high porosity and high water absorption. To achieve the reuse of resources, the researchers use microbial mineralization methods to further reinforce RAs. In this paper, the effect of the microbial carbonic anhydrase mineralization method on the water absorption of RAs was investigated, and the macroscopic analysis was performed by determining the indexes of water absorption and apparent density of RAs before and after the modification, and the microscopic analysis of RAs by using the methods of SEM, XRD, DSC, and EDS as well. According to the microscopic analysis, the mineralization products of microorganisms are calcium carbonate crystals, and with the increase in microbial liquid concentration, the water absorption rate of RAs shows a trend of decreasing and then increasing, and it can be found through the microscopic morphology that abundant mineralization products attached to the surface of the aggregate lead to the surface of the aggregate becoming rougher and more porous. The method of soaking the RAs in 3% bacterial solution and 0.1 mol/L calcium acetate solution followed by carbonation with 20% CO2 resulted in a 4.85% reduction in water absorption.
RESUMEN
INTRODUCTION: Mixed gonadal dysgenesis (MGD) is a rare disorder of sexual development. The management of MGD is challenging since the disease significantly impacts a patient's growth, hormone balance, and gonadal development. This article used a large population and a long follow-up period for its analysis. OBJECTIVES: This study aims to summarize the gender determination basis and analyze the long-term follow-up of mixed gonadal dysgenesis. METHODS: A total of 45 patients' clinical data were summarized and analyzed. Patients were divided by gender. Next, we followed up regarding the occurrence of complications after surgery, the patients' satisfaction with external genitalia appearance, the growth of the patients, counting the surgical pattern the incidence of surgical complications and the development of the patients' growth. All patients included in this study underwent chromosomal karyotype analysis, abdomen exploration, and pathological biopsy. After sex determination, 7 patients who were raised as female underwent clitoroplasty, and bilateral gonadectomy. 38 male patients underwent urethroplasty + one-sided gonadectomy. RESULTS: Patient follow-up started in the third month after surgery. Female patients reported no surgery-related complications, while 14 male patients showed surgery-related complications. Additionally, 20 male patients (60.6 %) had a lower height compared to normal peers, 12 of which (36.4 %) were lower than the second standard deviation of the height of normal peers. CONCLUSION: The clinical manifestations of mixed gonadal dysgenesis are variable, and the management is complicated. Children's gonadal function, external genital conditions, psychological evaluation, and parents' wishes should be considered before sex determination. In China, most patients are raised as males with a high incidence of postoperative complications. We found that short stature is a common feature in male patients, thus their height and growth should be carefully supervised. Patients should pay attention to their sexual function and sexual potential during adulthood.