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1.
Front Pharmacol ; 15: 1419369, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39086394

RESUMEN

Background: High-intensity chemotherapy can cause life-threatening complications in pediatric patients. Therefore, this study investigated safety and efficacy of long-acting pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF; Jinyouli®) in children undergoing high-intensity chemotherapy. Methods: Treatment-naive patients received post-chemotherapy PEG-rhG-CSF as primary prophylaxis for two cycles. The primary endpoints were drug-related adverse events (AEs) and bone pain scores. Secondary endpoints included grade 3-4 neutropenia, duration of neutropenia recovery, absolute neutrophil count changes, febrile neutropenia (FN), reduced chemotherapy intensity, antibiotic usage, and AE severity. The cost-effectiveness of PEG-rhG-CSF was compared with that of rhG-CSF (Ruibai®). Results: Here, 307 and 288 patients underwent one and two PEG-rhG-CSF cycles, respectively. Ninety-one patients experienced drug-related AEs, primarily bone pain (12.7%). Moreover, Grade 3-4 neutropenia and FN were observed. Median FN durations were 3.0 days in both cycles. No drug-related delays were observed during chemotherapy. One patient experienced grade 4 neutropenia-induced reduction in chemotherapy intensity during cycle 2. In total, 138 patients received antibiotics. PEG-rhG-CSF exhibited superior cost-effectiveness compared to rhG-CSF. Conclusion: Our findings indicate that PEG-rhG-CSF is safe, efficient, and cost-effective in pediatric patients undergoing high-intensity chemotherapy, providing preliminary evidence warranting further randomized controlled trials.

2.
World J Gastrointest Surg ; 16(7): 2119-2126, 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39087108

RESUMEN

BACKGROUND: Surgical resection is the cornerstone treatment for colorectal cancer. Rapid rehabilitation care predicated on evidence-based medical theory aims to improve postoperative nursing care, subsequently reducing the physical and mental traumatic stress response and helping patients who undergo surgery recover rapidly. AIM: To assess the effect of rapid rehabilitation care on clinical outcomes, including overall postoperative complications, anastomotic leaks, wound infections, and intestinal obstruction in patients with colorectal cancer. METHODS: We searched the PubMed, Web of Science, Embase, Elsevier Science Direct, and Springer Link databases from January 1, 2010, to January 1, 2024, to screen eligible studies on rapid rehabilitation care among patients who underwent colorectal cancer surgery. Patients were screened based on the inclusion and exclusion criteria. RevMan 5.4 software was used for statistical analysis of the data. RESULTS: Twelve studies were enrolled, which included 2420 patients. The results showed that rapid rehabilitation care decreased the incidence of overall postoperative complications (OR: 0.44, 95%CI: 0.26-0.74, P = 0.002), anastomotic leaks (OR: 0.68, 95%CI: 0.41-1.12, P = 0.13), wound infections (OR: 0.45, 95%CI: 0.29-0.72, P = 0.0007), and intestinal obstruction (OR: 0.54, 95%CI: 0.34-0.86, P = 0.01) compared to conventional care. Further trials and studies are needed to confirm these results. CONCLUSION: Rapid rehabilitation care decreased the occurrence of postoperative complications, anastomotic leaks, wound infections, and intestinal obstruction compared to conventional care in patients who underwent colorectal surgery. Therefore, promoting the application of rapid rehabilitation care in clinical practice cannot be overemphasized.

3.
Int J Biol Macromol ; 277(Pt 3): 134315, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39094886

RESUMEN

With the increasing demand for food foaming, how to enhance the foaming properties of protein has gradually become the research focus. This work studied the effect of synephrine (SY) on foaming properties, structure properties, and physicochemical properties of soybean protein isolate (SPI). When the mass ratio of SY to SPI was 1:2, compared with SPI alone, the foam capacity and foam stability of the SY-SPI complex were significantly enhanced. Optical microscopy and confocal laser scanning microscope showed that the improvement in foaming performance was mainly due to the reduction of bubble size and uniform protein distribution. Circular dichroism spectrum and fluorescence spectra indicated that the hydrogen bond of SPI was destroyed and blue shifted with the addition of SY. What's more, the absolute value of Zeta potential, solubility, and hydrophobicity all increased, while the particle size decreased. As a result of molecular docking, surface hydrogen bonds, Van der Waals forces and hydrophobic interactions are the main driving forces. The addition of SY and SPI improved the specific volume and texture of angel cake. This study shows that SY has the potential to be developed into a new type of blowing agent.


Asunto(s)
Enlace de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Polifenoles , Solubilidad , Proteínas de Soja , Proteínas de Soja/química , Polifenoles/química , Simulación del Acoplamiento Molecular , Fenómenos Químicos , Tamaño de la Partícula , Glycine max/química
4.
Pediatr Res ; 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39025934

RESUMEN

BACKGROUND: Extremely preterm infants (EPIs) are at high-risk of white matter injury (WMI), leading to long-term neurodevelopmental impairments. We aimed to develop nomograms for WMI. METHODS: The study included patients from 31 provinces, spanning ten years. 6074 patients before 2018 were randomly divided into a training and internal validation group (7:3). The external validation group comprised 1492 patients from 2019. Predictors were identified using the least absolute shrinkage and selection operator (LASSO) and multivariable logistic regression and nomograms were constructed. Models' performance was evaluated using receiver operating characteristic (ROC), decision curve analysis (DCA) and calibration curves. RESULTS: The prenatal nomogram included multiple gestation, premature rupture of membranes (PROM), chorioamnionitis, prenatal glucocorticoids, hypertensive disorder complicating pregnancy (HDCP) and Apgar 1 min, with area under the curve (AUC) of 0.805, 0.816 and 0.799 in the training, internal validation and external validation group, respectively. Days of mechanical ventilation (MV), shock, patent ductus arteriosus (PDA) ligation, intraventricular hemorrhage (IVH) grade III-IV, septicemia, hypothermia and necrotizing enterocolitis (NEC) stage II-III were identified as postpartum predictors. The AUCs were 0.791, 0.813 and 0.823 in the three groups, respectively. DCA and calibration curves showed good clinical utility and consistency. CONCLUSION: The two nomograms provide clinicians with precise and efficient tools for prediction of WMI. IMPACT: This study is a large-sample multicenter study, spanning 10 years. The two nomograms are convenient for identifying high-risk infants early, allowing for reducing poor prognosis.

5.
Food Chem ; 460(Pt 2): 140607, 2024 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-39068804

RESUMEN

The high temperature induces conformational changes in ß-glucosidase, making it inactive and limiting its application field. In this paper, the effect of trehalose on the thermostability of ß-glucosidase from low-moisture Hevea brasiliensis seeds was investigated. The results showed that the residual enzyme activities of ß-glucosidase supplemented with trehalose after high-temperature treatment were significantly higher than that of the control group. The improvement of thermostability could be explained by low-field nuclear magnetic resonance (LF-NMR) and molecular dynamics (MD) simulations at the molecular level. Moreover, adding trehalose increased the water activity and water content of ß-glucosidase, leading to a more stable conformation. Trehalose replaced some water and formed a stable network of hydrogen bonds with protein and surrounding water. The glass formed by trehalose also reduced molecular movement, thus providing good protection for enzymes.


Asunto(s)
Estabilidad de Enzimas , Simulación de Dinámica Molecular , Trehalosa , Agua , beta-Glucosidasa , Trehalosa/química , Trehalosa/metabolismo , beta-Glucosidasa/química , beta-Glucosidasa/metabolismo , Agua/química , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Calor , Semillas/química , Semillas/enzimología , Enlace de Hidrógeno
6.
Artículo en Inglés | MEDLINE | ID: mdl-38739513

RESUMEN

In the real world, data distributions often exhibit multiple granularities. However, the majority of existing neighbor-based machine-learning methods rely on manually setting a single-granularity for neighbor relationships. These methods typically handle each data point using a single-granularity approach, which severely affects their accuracy and efficiency. This paper adopts a dual-pronged approach: it constructs a multi-granularity representation of the data using the granular-ball computing model, thereby boosting the algorithm's time efficiency. It leverages the multi-granularity representation of the data to create tailored, multi-granularity neighborhood relationships for different task scenarios, resulting in improved algorithmic accuracy. The experimental results convincingly demonstrate that the proposed multi-granularity neighbor relationship effectively enhances KNN classification and clustering methods. The source code has been publicly released and is now accessible on GitHub at https://github.com/xjnine/MGNR.

7.
Altern Ther Health Med ; 30(5): 148-154, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38639627

RESUMEN

Objective: Epstein-Barr virus (EBV) is a common virus that infects a large portion of the world's population, with most people becoming infected during childhood or adolescence. The objective of this article is to analyze the clinical and laboratory examination results of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) in children, summarize its characteristics, identify critically ill children as soon as possible, and provide a basis for diagnosis and treatment. Method: The retrospective analysis in this study involved collecting data from 34 cases of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) admitted to Hebei Children's Hospital from January 2019 to December 2022. The inclusion criteria for the cases studied likely included confirmed diagnosis of EBV-HLH based on clinical symptoms, laboratory findings, and possibly viral testing results. Key parameters analyzed in the study may have included clinical manifestations, laboratory test results (e.g., levels of lactate dehydrogenase, sCD25, IL-10, calcium ions, glutathione aminotransferase, ferritin, alanine aminotransferase, D-dimer), survival rates, and other relevant indicators. Additionally, the cases were likely divided into high-risk groups (with multiple organ dysfunction or requiring ventilator-assisted ventilation) and non-risk groups for comparative analysis. Results: The results showed that 34 cases (100%) of EBV-HLH had elevated levels of lactate dehydrogenase, sCD25, IL-10, and decreased levels of calcium ions. 97.1% of the children had a fever and elevated levels of glutathione aminotransferase and ferritin, with an 8-week survival rate of 91.2%. The levels of alanine aminotransferase, alanine aminotransferase, lactate dehydrogenase, ferritin, D-dimer, and sCD25 in critically ill children were significantly higher than those in the non-critically ill group, with statistical significance (P < .05). The decreased levels of calcium ions in EBV-HLH patients suggest potential tissue damage and disruption of calcium homeostasis, contributing to the systemic manifestations of the disease. Compared with non-critical recombinant albumin, the decrease in critical recombinant albumin was statistically significant (P < .05). Conclusion: Significant changes in laboratory results can contribute to the early diagnosis and targeted treatment of EBV-HLH, especially for critically ill children. We should pay timely attention to laboratory examinations, diagnosis and treatment, and avoid or reduce the occurrence of adverse consequences. Based on the results of the study on Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) in children, specific strategies and criteria can be proposed to aid in the early identification of critically ill children with this condition in clinical practice: Clinical Screening, Risk Stratification, Early Intervention, Multidisciplinary Management and Educational Measures.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Linfohistiocitosis Hemofagocítica , Humanos , Linfohistiocitosis Hemofagocítica/virología , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/sangre , Femenino , Masculino , Estudios Retrospectivos , Niño , Preescolar , Infecciones por Virus de Epstein-Barr/complicaciones , Lactante , Herpesvirus Humano 4 , Adolescente
8.
Pain Manag Nurs ; 25(1): 88-92, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37867077

RESUMEN

BACKGROUND: Knee osteoarthropathy is one of the most common degenerative joint diseases in the elderly, total knee arthroplasty (TKA) is the most commonly used treatment for end-stage knee osteoarthropathy. Negative emotions such as anxiety have been extensively documented in knee osteoarthropathy patients. AIM: This study aimed to investigate the Emotional Contagion during hospitalization in patients undergoing TKA. METHODS: Eligible subjects were divided into three case groups according to their anxiety states and bed arrangement. All subjects underwent a unilateral, cemented TKA under general anesthesia. Post-operative recovery outcomes including pain, pain behavior and physical function were recorded pre-operation, 1-day, 1 week, 2-weeks, 1-month and 3-months post-operation. RESULTS: A total of 38 subjects were included in the final analysis. Subjects with anxiety had higher Visual Analogue Scale pain scores, PROMIS-Pain Behavior scores than subjects without anxiety in the Contagion Group preoperation (p ≤ .05). Non-anxiety subjects hospitalized in beds physically adjacent to anxiety subjects experienced more severe pain and poorer function (p ≤ .05). After discharge, all clinical outcomes gradually became lower than anxiety subjects in the Contagion Group, reaching levels similar to non-anxiety subjects in the No Contagion Group within 1 month (p>.05). CONCLUSIONS: This study showed that patients with anxiety may have an "Adjacent Bed Effect" on patients with TKA in the adjacent bed, which may be associated with poorer postoperative recovery, including pain and physical function. We speculate this phenomenon can be effectively avoided by the nursing team through accurately assessing psychological status and reasonable bed arrangements in the inpatient assessment phase.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Osteoartritis de la Rodilla , Humanos , Anciano , Resultado del Tratamiento , Periodo Posoperatorio , Dolor/complicaciones
9.
Acta Pharmaceutica Sinica ; (12): 35-42, 2024.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1005437

RESUMEN

Sesquiterpenoids are widely found in nature, while nitrobenzoyl sesquiterpenoids are relatively rare. Twelve natural nitrobenzoyl sesquiterpenoids were all derived from marine Aspergillus fungi, which are typical natural products with marine characteristics. These natural products exhibit good antitumor, antiviral, and inhibition of osteoclast differentiation activity, especially in the treatment of osteoclast-related diseases, showing good medicinal development value. This article reviews the natural product sources, chemical structure, chemical synthesis, biosynthesis, bioactivity, and pharmacological mechanisms of nitrobenzoyl sesquiterpenoids and predicts and discusses their absorption, distribution, metabolism, excretion, toxicity (ADME/T), and drug-likeness, providing a comprehensive understanding of the natural products of nitrobenzoyl sesquiterpenoids from marine sources and their potential for pharmaceutical development.

10.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(11): 1150-1155, 2023 Nov 15.
Artículo en Chino | MEDLINE | ID: mdl-37990460

RESUMEN

OBJECTIVES: To investigate the expression and significance of jumonji domain-containing protein 2B (JMJD2B) and hypoxia-inducible factor-1α (HIF-1α) in non-Hodgkin's lymphoma (NHL) tissues in children. METHODS: Immunohistochemistry was used to detect the expression of JMJD2B and HIF-1α in lymph node tissue specimens from 46 children with NHL (observation group) and 24 children with reactive hyperplasia (control group). The relationship between JMJD2B and HIF-1α expression with clinicopathological characteristics and prognosis in children with NHL, as well as the correlation between JMJD2B and HIF-1α expression in NHL tissues, were analyzed. RESULTS: The positive expression rates of JMJD2B (87% vs 21%) and HIF-1α (83% vs 42%) in the observation group were higher than those in the control group (P<0.05). The expression of JMJD2B and HIF-1α was correlated with serum lactate dehydrogenase levels and the risk of international prognostic index in children with NHL (P<0.05). The expression of JMJD2B was positively correlated with the HIF-1α expression in children with NHL (rs=0.333, P=0.024). CONCLUSIONS: JMJD2B and HIF-1α are upregulated in children with NHL, and they may play a synergistic role in the development of pediatric NHL. JMJD2B can serve as a novel indicator for auxiliary diagnosis, evaluation of the severity, treatment guidance, and prognosis assessment in pediatric NHL.


Asunto(s)
Subunidad alfa del Factor 1 Inducible por Hipoxia , Linfoma no Hodgkin , Humanos , Niño , Pronóstico , Hipoxia
11.
Opt Express ; 31(16): 26335-26343, 2023 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-37710496

RESUMEN

In this work, we present a new time-bin phase-encoding quantum key distribution (QKD), where the transmitter utilizes an inherently stable Sagnac-type interferometer, and has comparable electrical requirements to existing polarization or phase encoding schemes. This approach does not require intensity calibration and is insensitive to environmental disturbances, making it both flexible and high-performing. We conducted experiments with a compact QKD system to demonstrate the stability and secure key rate performance of the presented scheme. The results show a typical secure key rate of 6.2 kbps@20 dB and 0.4 kbps@30 dB with channel loss emulated by variable optical attenuators. A continuous test of 120-km fiber spool shows a stable quantum bit error rate of the time-bin basis within 0.4%∼0.6% over a consecutive 9-day period without any adjustment. This intrinsically stable and compatible scheme of time-bin phase encoding is extensively applicable in various QKD experiments, including BB84 and measurement-device-independent QKD.

12.
PLoS Genet ; 19(7): e1010867, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37523410

RESUMEN

Many filamentous fungi produce plant-polysaccharide-degrading enzymes (PPDE); however, the regulatory mechanism of this process is poorly understood. A Gal4-like transcription factor, CxrA, is essential for mycelial growth and PPDE production in Penicillium oxalicum. Its N-terminal region, CxrAΔ207-733 is required for the regulatory functions of whole CxrA, and contains a DNA-binding domain (CxrAΔ1-16&Δ59-733) and a methylated arginine (R) 94. Methylation of R94 is mediated by an arginine N-methyltransferase, PRMT2 and appears to induce dimerization of CxrAΔ1-60. Overexpression of prmt2 in P. oxalicum increases PPDE production by 41.4-95.1% during growth on Avicel, compared with the background strain Δku70;hphR+. Another arginine N-methyltransferase, PRMT3, appears to assist entry of CxrA into the nucleus, and interacts with CxrAΔ1-60 in vitro under Avicel induction. Deletion of prmt3 resulted in 67.0-149.7% enhanced PPDE production by P. oxalicum. These findings provide novel insights into the regulatory mechanism of fungal PPDE production.


Asunto(s)
Penicillium , Proteína-Arginina N-Metiltransferasas , Proteína-Arginina N-Metiltransferasas/genética , Penicillium/genética , Celulosa , Arginina
13.
Langmuir ; 39(25): 8698-8709, 2023 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-37314954

RESUMEN

Traditional hydrogels with a single-crosslinked network structure suffer from poor stretchability, low sensitivity, and easy contamination, which seriously affect their practical application in the strain sensor field. To overcome these shortcomings, herein, a multiphysical crosslinking strategy (ionic crosslinking and hydrogen bonding) was designed to prepare a hydrogel strain sensor based on chitosan quaternary ammonium salt (HACC)-modified P(AM-co-AA) (acrylamide-co-acrylic acid copolymer) hydrogels. The ionic crosslinking for the double-network P(AM-co-AA)/HACC hydrogels was achieved by an immersion method with Fe3+ as crosslinking sites, which crosslinked with the amino group (-NH2) on HACC and the carboxyl group (-COOH) on P(AM-co-AA) and enabled the hydrogels to recover and reorganize rapidly, resulting in a hydrogel-based strain sensor with excellent tensile stress (3 MPa), elongation (1390%), elastic modulus (0.42 MPa), and toughness (25 MJ/m3). In addition, the prepared hydrogel exhibited high electrical conductivity (21.6 mS/cm) and sensitivity (GF = 5.02 at 0-20% strain, GF = 6.84 at 20-100% strain, and GF = 10.27 at 100-480% strain). Furthermore, the introduction of HACC endowed the hydrogel with excellent antibacterial properties (up to 99.5%) and excellent antibacterial activity against bacteria of three forms, bacilli, cocci, and spores. The flexible, conductive, and antibacterial hydrogel can be applied as a strain sensor for real-time detection of human motions such as joint movement, speech, and respiration, which exhibits a promising application prospect in wearable devices, soft robotic systems, and other fields.

14.
Sci Rep ; 13(1): 9114, 2023 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-37277431

RESUMEN

When plates with edge cracks in the rolling process is straightened by cyclic tensile and compressive stress, the tip of edge crack always accompanied by stress concentration, which leads to crack propagation. In this paper, damage parameters are imported into the plate straightening model based on determining the GTN damage parameters of magnesium alloy materials by inverse finite element calibration method, the influence of different straightening process schemes and prefabricated V-shaped crack geometry on crack growth is analyzed through the way of the combination of simulation and straightening experiment. The results show that the peak values of equivalent stress and equivalent strain under each straightening roll appear at the crack tip. The value of longitudinal stress and equivalent stain decrease with the distance to crack tip becomes larger. The peak value of longitudinal stress appears when the crack circumferential angle is about 100°, and the crack tip is easy to form crack propagation; when the plate passes roll 2 and roll 4, the equivalent stress and strain concentration at the crack tip are most obvious; when the reduction reaches a certain degree, the void volume fraction (VVF) reaches the VVF of the material breaking; with the increase of the entrance reduction, the number of VVF at the crack tip which reaches the material fracture increases, and the length of crack propagation increases; the stress concentration at the tip of V-shaped crack with large length-width ratio is obvious, and the VVF is more likely to reach the VVF at the time of material fracture, crack initiates and propagates easily.

15.
Allergol. immunopatol ; 51(3): 28-35, 01 mayo 2023. tab
Artículo en Inglés | IBECS | ID: ibc-219810

RESUMEN

Background: L-Asparaginase (L-asp), the unconjugated form of polyethylene glycol-conjugated L-asparaginase (PEG-asp), regulates T cell stimulation, antibody production, and lysosomal protease activity to mediate PEG-asp-related anaphylaxis. This study aimed to investigate the relation of L-asp activity and anti-L-asp antibody with anaphylaxis risk and non-anaphylaxis adverse reaction risk in childhood acute lymphoblastic leukemia (ALL) patients who underwent PEG-asp contained therapy. Methods: In total, 170 childhood ALL patients underwent PEG-asp-contained treatment and their L-asp activity and anti-L-asp antibody were detected on the 7th day after treatment initiation. Results: There were 27 (15.9%) patients who had PEG-asp-related adverse reaction: 17 (10.0%) patients experienced PEG-asp-related anaphylaxis and 14 (8.2%) patients experienced PEG- asp-related non-anaphylaxis adverse reaction. Moreover, L-asp activity was negatively related to anti-L-asp antibody in childhood ALL patients (P<0.001). Elevated L-asp activity was associated with the absence of PEG-asp-related anaphylaxis (P<0.001), PEG-asp-related non-anaphylaxis adverse reaction (P=0.004), and PEG-asp-related adverse reaction (P<0.001). However, the anti- L-asp antibody displayed opposite trend similar to L-asp activity. Receiver operating characteristic (ROC) curve analyses exhibited L-asp activity and anti-L-asp antibody exhibited superior predictive values in estimating PEG-asp-related anaphylaxis risk with area under curve (AUC) of 0.955 and 0.905, respectively compared to PEG-asp-related non-anaphylaxis adverse reaction risk with AUC of 0.730 and 0.675, respectively. Besides, patients with de novo disease, higher risk stratification, and allergic history showed trends linked with PEG-asp-related anaphylaxis risk. Conclusion: The monitoring of L-asp activity and anti-L-asp antibody maybe useful for early estimation and prevention of PEG-asp-related anaphylaxis in childhood ALL management (AU)


Asunto(s)
Humanos , Masculino , Femenino , Preescolar , Anafilaxia/prevención & control , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Asparaginasa/metabolismo , Asparaginasa/antagonistas & inhibidores , Autoanticuerpos
16.
Allergol Immunopathol (Madr) ; 51(3): 28-35, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37169557

RESUMEN

BACKGROUND: L-Asparaginase (L-asp), the unconjugated form of polyethylene glycol-conjugated L-asparaginase (PEG-asp), regulates T cell stimulation, antibody production, and lysosomal protease activity to mediate PEG-asp-related anaphylaxis. This study aimed to investigate the relation of L-asp activity and anti-L-asp antibody with anaphylaxis risk and non-anaphylaxis adverse reaction risk in childhood acute lymphoblastic leukemia (ALL) patients who underwent PEG-asp contained therapy. METHODS: In total, 170 childhood ALL patients underwent PEG-asp-contained treatment and their L-asp activity and anti-L-asp antibody were detected on the 7th day after treatment initiation. RESULTS: There were 27 (15.9%) patients who had PEG-asp-related adverse reaction: 17 (10.0%) patients experienced PEG-asp-related anaphylaxis and 14 (8.2%) patients experienced PEG- asp-related non-anaphylaxis adverse reaction. Moreover, L-asp activity was negatively related to anti-L-asp antibody in childhood ALL patients (P<0.001). Elevated L-asp activity was associated with the absence of PEG-asp-related anaphylaxis (P<0.001), PEG-asp-related non-anaphylaxis adverse reaction (P=0.004), and PEG-asp-related adverse reaction (P<0.001). However, the anti- L-asp antibody displayed opposite trend similar to L-asp activity. Receiver operating characteristic (ROC) curve analyses exhibited L-asp activity and anti-L-asp antibody exhibited superior predictive values in estimating PEG-asp-related anaphylaxis risk with area under curve (AUC) of 0.955 and 0.905, respectively compared to PEG-asp-related non-anaphylaxis adverse reaction risk with AUC of 0.730 and 0.675, respectively. Besides, patients with de novo disease, higher risk stratification, and allergic history showed trends linked with PEG-asp-related anaphylaxis risk. CONCLUSION: The monitoring of L-asp activity and anti-L-asp antibody maybe useful for early estimation and prevention of PEG-asp-related anaphylaxis in childhood ALL management.


Asunto(s)
Anafilaxia , Asparaginasa , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Anafilaxia/inducido químicamente , Asparaginasa/efectos adversos , Asparaginasa/uso terapéutico , Biomarcadores , Polietilenglicoles/efectos adversos , Polietilenglicoles/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/inducido químicamente , Niño
17.
Cancer Med ; 12(13): 14130-14137, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37183837

RESUMEN

BACKGROUND: Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) can be used in pediatric patients. This study assessed the safety and efficacy of PEG-rhG-CSF as a primary prophylactic drug against neutropenia after chemotherapy in pediatric patients with solid tumors or non-Hodgkin lymphoma (NHL). PATIENTS AND METHODS: This phase II study (between October 2020 and March 2022) enrolled pediatric patients with solid tumors or NHL treated with high-intensity chemotherapy and with grade ≥3 myelosuppression for at least 14 days during chemotherapy. Prophylactic PEG-rhG-CSF was given at 100 µg/kg body weight (maximum total dosage of 6 mg) once 24-48 h following chemotherapy for two cycles. The primary endpoint was the incidence of PEG-rhG-CSF-related adverse events (AEs). The key secondary endpoints were the rates of grade 3/4 neutropenia and febrile neutropenia (FN). RESULTS: This study included 160 pediatric patients with a median age of 6.22 (0.29, 18.00) years. Fifty-eight patients (36.25%) were diagnosed with sarcoma. AEs potentially related to PEG-rhG-CSF included bone pain (n = 32), fatigue (n = 21), pain at the injection site (n = 21), and myalgia (n = 20). The rates of grade 3/4 neutropenia and FN during treatment were 57.28% and 29.45%, respectively. CONCLUSION: PEG-rhG-CSF is well tolerated and effective in pediatric patients with solid tumors or NHL. These findings should be substantiated with further trials. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04547829.


Asunto(s)
Neoplasias Pulmonares , Linfoma no Hodgkin , Neutropenia , Humanos , Niño , Neoplasias Pulmonares/tratamiento farmacológico , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/etiología , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Polietilenglicoles/efectos adversos , Proteínas Recombinantes/efectos adversos , Neutropenia/inducido químicamente , Neutropenia/prevención & control , Neutropenia/tratamiento farmacológico , Dolor/inducido químicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
18.
J Am Chem Soc ; 145(19): 10463-10469, 2023 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-37129915

RESUMEN

γ-Lactams are valuable heterocycles in synthetic chemistry and drug development. Here, we report a reductive aza-Pauson-Khand reaction (aza-PKR) of an alkyne, a nitrile, and Co2(CO)8. A wide array of bicyclic α,ß-unsaturated γ-lactams containing two adjacent stereocenters, including an all-carbon quaternary center, from alkyne-tethered malononitriles are efficiently accessed in high diastereoselectivity. Preliminary mechanistic investigations by experiments and DFT calculations reveal that the reaction undergoes an aza-PKR process followed by a in situ reduction. The reducing reagent generated in situ from water also provides a practical tool for deuterium incorporation into the γ-position of lactams using D2O as the deuterium source. This study represents a new mode for [2 + 2 + 1] cycloaddition that enables the direct use of nitrile in aza-heterocycle synthesis.

19.
Exp Brain Res ; 241(5): 1215-1226, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36961552

RESUMEN

The central nervous system (CNS) consists of neuron and non-neuron cells including neural stem/precursor cells (NSPCs), neuroblasts, glia cells (mainly astrocyte, oligodendroglia and microglia), which thereby form a precise and complicated network and exert diverse functions through interactions of numerous bioactive ingredients. MicroRNAs (miRNAs), with small size approximately ~ 21nt and as well-documented post-transcriptional key regulators of gene expression, are a cluster of evolutionarily conserved endogenous non-coding RNAs. More than 2000 different miRNAs has been discovered till now. MicroRNA-124(miR-124), the most brain-rich microRNA, has been validated to possess important functions in the central nervous system, including neural stem cell proliferation and differentiation, cell fate determination, neuron migration, synapse plasticity and cognition, cell apoptosis etc. According to recent studies, herein, we provide a review of this conversant miR-124 to further understand the potential functions and therapeutic and clinical value in brain diseases.


Asunto(s)
Enfermedades del Sistema Nervioso Central , MicroARNs , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Enfermedades del Sistema Nervioso Central/metabolismo , Sistema Nervioso Central , Neuroglía , Diferenciación Celular/genética
20.
Heliyon ; 9(1): e12355, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36685370

RESUMEN

Many organisms in nature such as beetles and cacti can survive in arid places by their own surface structures that are still able to collect mist. These surfaces have micro-nano structures that maintain a very low adhesion, allowing them to continuously collect and transport water. Here, we used a light curing three dimensional molding process to create a template for a water harvesting system inspired by the back of a beetle, a hydrogel-like beetle back surface for water transport. By changing the curvature structure of the water evacuation channels and altering the hydrophilic and hydrophobic properties of the surface, the designed large-scale artificial water harvesting study was made possible. The results show that if the surface has a proper curvature structure and hydrophobic density, the water collection on the super-impregnated surface is much higher than that on an ordinary hydrophobic surface. Based on this, a new efficient and environmentally friendly water collection scheme is proposed. The data show that the triangular tip structure imitating beetle-backed hydrogel surface collects the highest amount of water with a water weight of 16 g in 2 h. This study offers interesting prospects for designing a new generation of structural materials with a bionic structure distribution for high-efficiency water harvesting. The results of the study are useful for pushing the improvement of environmental-friendly water collection, transport and separation devices. Abbreviations: The dorsal shape of the beetle's back is critical for water collection. In this work, while redesigning the shape of the back of the beetle, the method of 3D printing the beetle back template was used to prepare the beetle back made of hydrogel, which greatly improved the water collection performance and has certain engineering application prospects.

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