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1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(2): 370-375, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38660838

RESUMO

OBJECTIVE: To analyze the efficacy and safety of flumatinib, a second-generation tyrosine kinase inhibitor (TKI) independently developed in China, in patients with chronic myelogenous leukemia in chronic phase (CML-CP) who falied first-line and second-line treatment. METHODS: The clinical data of 30 CML-CP patients treated with flumatinib in Lianyungang First People's Hospital from January 2020 to September 2022 were collected retrospectively. Among them, 15 patients who received imatinib first-line treatment but failed treatment were included in the second-line group, and the other 15 patients who failed second-line treatment with nilotinib or dasatinib were included in the third-line group. The hematological and molecular responses of the patients in the two groups at 3, 6 and 12 months of treatment, and the event-free survival (EFS) and adverse reactions of patients at the end of follow-up were statistical analyzed. RESULTS: At 3, 6, and 12 months of treatment, 10, 11, and 12 patients in the second line group achieved major molecular response (MMR), which was higher than that of 3, 4, and 5 patients in the third line group (P =0.010, P =0.011, P =0.010). At 3 months of treatment, 12 and 13 patients achieved complete hematological response (CHR) and early molecular response (EMR) in the second-line group, which was higher than that of 9 and 13 patients in the third-line group, but the difference between the two groups was not statistically significant (P =0.232, P =1.000); At 6 and 12 months of treatment, 6 and 7 patients in the second-line group achieved MR4.5, which were higher than of 3 and 2 cases in the third-line group, but the difference was not statistically significant (P =0.427, P =0.713). The hematological adverse reactions of patients in the second-line group during treatment the period were mainly grade 1-2 thrombocytopenia and anemia, and no grade 3-4 of adverse reactions occurred. In the third-line group, there were 2 cases of grade 1-2 thrombocytopenia, grade 1-2 anemia and white blood cell 3 cases were reduced each, 1 case of grade 3-4 anemia, 2 cases of grade 3-4 neutropenia. The non-hematological adverse reactions in the second-line group were rash (2 cases), headache (1 case), diarrhea (1 case), fatigue (1 case), limb pain (1 case). There were 1 cases of diarrhea, 1 cases of nausea, and 1 cases of edema in the third-line group. There was no statistical significance in hematological and non-hematological adverse reactions between the two groups of patients (P >0.05). At the end of follow-up, the EFS rate of patients in the second-line group was higher than that in the third-line group (100% vs 93.3%), but the difference was not statistically significant (P =0.317). CONCLUSION: The second-generation TKI flumatinib independently developed in China, has good curative effect and safety for CML-CP patients who failed first-line and second-line treatment.


Assuntos
Aminopiridinas , Benzamidas , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Estudos Retrospectivos , Benzamidas/uso terapêutico , Feminino , Masculino , Aminopiridinas/efeitos adversos , Mesilato de Imatinib/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Pirimidinas/efeitos adversos , Pessoa de Meia-Idade , Morfolinas/uso terapêutico , Dasatinibe/uso terapêutico , Dasatinibe/efeitos adversos , Adulto
2.
Chin J Integr Med ; 30(4): 291-298, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38433155

RESUMO

OBJECTIVE: To investigate the immediate effects of electro-acupuncture (EA) on endometrial blood flow among recurrent implantation failure (RIF) patients. METHODS: Eighty RIF patients, enrolled from March 2022 to December 2022, were randomly allocated into either the EA group (40 cases) or the waiting-list (WL) group (40 cases) by using a random number table. The EA group underwent acupuncture at points of Shenting (GV 24), Baihui (GV 4), Benshen (GB 13), bilateral Zigong (EX-CA 1), Huangshu (KI 16), Sanyinjiao (SP 6) and Xuehai (SP10), and electric acupuncture apparatus was connected to EX-CA 1, KI 16, SP 6, and SP 10 with disperse-dense waves at 4/20 Hz frequencies for 30 min after transvaginal ultrasound, while the WL group received no intervention. The primary outcome measured was the endometrial volume blood flow. The secondary outcomes included the bilateral uterine artery index, endometrial volume, endometrial blood flow type, vascular distribution index (VIMV) for endometrial and ovary, clinical pregnancy rate, and embryo implantation rate. RESULTS: In the EA group, there was a notable decrease in the bilateral pulsatility index and a significant improvement in the endometrial blood flow type post-EA (P<0.05). Both the endometrial blood flow type and VIMV for the endometrium and right ovary were markedly higher in the EA group compared to the WL group post-treatment (P<0.05). Conversely, no significant disparities were observed in vascular index, flow index, vascular blood flow index, uterine arterial blood flow indices, endometrial volume, clinical pregnancy rate and embryo implantation rate between the two groups after treatment (P>0.05). Besides, no adverse events related to EA were observed. CONCLUSIONS: EA can promptly ameliorate VIMV for the endometrial and right ovary, and endometrial blood flow type. Future randomized controlled trials are warranted to investigate the long-term effects of EA on blood flow of RIF patients and its implications for pregnancy outcomes. (Trial registration No. ChiCTR2200057377).


Assuntos
Terapia por Acupuntura , Eletroacupuntura , Gravidez , Feminino , Humanos , Endométrio/irrigação sanguínea , Taxa de Gravidez , Resultado da Gravidez , Transferência Embrionária , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Turk J Gastroenterol ; 35(1): 41-47, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38454276

RESUMO

BACKGROUND/AIMS: The aim of this study was to explore the risk factors for the incidence of gastroscopy-assisted capsule endoscopy and the small bowel transit time in pediatric patients who underwent capsule endoscopy examination. MATERIALS AND METHODS: A retrospective analysis was performed to analyze the clinical data collected from pediatric patients who underwent capsule endoscopy examination. RESULTS: A total of 239 pediatric patients were enrolled in this study. About 196 (82.0%) patients completed the entire small bowel capsule endoscopy examination, while 3 (1.3%) patients were subjected to capsule retention. Only age, not gender, height, body weight, body mass index, chief complaint, and intestinal preparation medications, has been identified as a risk factor for the incidence of gastroscopy-assisted capsule endoscopy (P < .05) by multivariate logistic regression. Further analysis showed that the small bowel transit time in the self-swallowed group was shorter than that in the gastroscopy-assisted group, while no significant difference was obtained in other factors, including intestinal preparation medications, metoclopramide, and lesions in the small intestine, which did not significantly affect small bowel transit time compared with the corresponding control group (P > .05). CONCLUSION: A comprehensive assessment is required before performing capsule endoscopy, because age has been identified as a critical risk factor for the incidence of gastroscopy-assisted capsule endoscopy in pediatric patients.


Assuntos
Endoscopia por Cápsula , Humanos , Criança , Estudos Retrospectivos , Gastroscopia , Intestino Delgado/patologia , Fatores de Risco
4.
Fitoterapia ; 174: 105872, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38417681

RESUMO

A total of 19 resveratrol derivatives, including 12 imines and 7 amines, were synthesized, among which compounds 1, 5, 6, 7', 11', and 13 are new compounds. The anti-inflammatory and antitumor activities of these compounds were evaluated in vitro. The results revealed that compounds 1, 6, 8', 12, and 12' exhibited significant inhibitory effects (> 50%) on NO production at the concentration of 10 µM and their NO production inhibitory activities have a significant concentration-dependent ability. Additionally, compounds 8' and 12' showed promising COX-2 inhibitory activity, and the molecular docking analysis indicated their stable binding to multiple amino acid residues within the active pocket of COX-2 through hydrogen bonding. Moreover, compound 12' exhibited inhibitory effects on various tumor cell lines and induced apoptosis in MCF-7 breast cancer cells, which was not observed with resveratrol alone. Therefore, the N-substituted structural modification of resveratrol would have possibly enhanced the bioactivity of resveratrol and facilitated its application.


Assuntos
Antineoplásicos , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Resveratrol/farmacologia , Simulação de Acoplamento Molecular , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Relação Dose-Resposta a Droga , Desenho de Fármacos
5.
Cancer Gene Ther ; 31(1): 43-57, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37891404

RESUMO

Highly proliferative and metastatic tumors are constantly exposed to both intrinsic and extrinsic factors that induce adaptation to stressful conditions. Chronic adaptation to endoplasmic reticulum (ER) ER stress is common to many different types of cancers, and poses a major challenge for acquired drug resistance. Here we report that LAMC2, an extracellular matrix protein upregulated in many types of cancers, is localized in the ER of lung, breast, and liver cancer cells. Under tunicamycin-induced ER stress, protein level of LAMC2 is upregulated. Transfection of cancer cells with LAMC2 resulted in the attenuation of ER stress phenotype, accompanied by elevation in mitochondrial membrane potential as well as reduction in reactive oxygen species (ROS) levels and apoptosis. In addition, LAMC2 forms protein complexes with MYH9 and MYH10 to promote mitochondrial aggregation and increased ER-mitochondria interaction at the perinuclear region. Moreover, overexpression of LAMC2 counteracts the effects of ER stress and promotes tumor growth in vivo. Taken together, our results revealed that in complex with MYH9 and MYH10, LAMC2 is essential for promoting ER-mitochondria interaction to alleviate ER stress and allow cancer cells to adapt and proliferate under stressful conditions. This study provides new insights and highlights the promising potential of LAMC2 as a therapeutic target for cancer treatment.


Assuntos
Estresse do Retículo Endoplasmático , Mitocôndrias , Humanos , Estresse do Retículo Endoplasmático/genética , Mitocôndrias/genética , Mitocôndrias/metabolismo , Apoptose/genética , Linhagem Celular , Espécies Reativas de Oxigênio/metabolismo , Laminina/metabolismo , Laminina/farmacologia , Cadeias Pesadas de Miosina/genética , Cadeias Pesadas de Miosina/metabolismo , Cadeias Pesadas de Miosina/farmacologia
6.
Front Oncol ; 13: 1218128, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37731637

RESUMO

Objectives: Tumor grading is important for prognosis of pancreatic ductal adenocarcinoma (PDAC). In this study, we developed preoperative clinical-radiomics nomograms using features from contrast-enhanced CT (CECT), to discriminate high-grade and low-grade PDAC and predict overall survival (OS). Methods: In this single-center, retrospective study conducted from February 2014 to April 2021, consecutive PDAC patients who underwent CECT and had pathologically identified grading were randomized to training (n=200) and test (n=84) cohorts for development of model to predict histological grade based on radiomics scores from CECT (HGrad). Another 42 patients were used as external validation cohort of HGrad. A nomogram (HGnom) was constructed using radiomics score, CA12-5 and smoking to predict histological grade. A second nomogram (Pnom) was constructed using radiomics score, CA12-5, TNM, adjuvant treatment, resection margin and microvascular invasion to predict OS in radical resection patients (217 of 284). Results: Among 326 patients, 122 were high-grade (120 poorly differentiated and 2 undifferentiated). The HGrad yielded AUCs of 0.75 (95% CI: 0.64, 0.85) and 0.76 (95% CI: 0.60, 0.91) in test and validation cohorts. The HGnom achieved AUCs of 0.77 (95% CI: 0.66, 0.87), and the predicted grades calibrated well with actual grades (P=.13). OS was different between the grades predicted by radiomics scores (P=.01). The integrated AUC of the Pnom for predicting OS was 0.80 (95% CI: 0.75, 0.88). Conclusion: Compared with the HGrad using features from CECT, the HGnom demonstrated higher performance for predicting histological grade. The Pnom helped identify patients with high survival outcome in pancreatic ductal adenocarcinoma.

8.
Genes (Basel) ; 14(9)2023 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-37761869

RESUMO

Salidroside (Sal) possesses several pharmacological activities, such as antiaging, and anti-inflammatory, antioxidant, anticancer activities, and proliferation-promoting activities, but the effects of Sal on oocytes have rarely been reported. In the present study, we evaluated the beneficial effects of Sal, which is mainly found in the roots of Rhodiola. Porcine cumulus oocyte complexes were cultured in IVM medium supplemented (with 250 µmol/L) with Sal or not supplemented with Sal. The maturation rate in the Sal group increased from 88.34 ± 4.32% to 94.12 ± 2.29%, and the blastocyst rate in the Sal group increased from 30.35 ± 3.20% to 52.14 ± 7.32% compared with that in the control group. The experimental groups showed significant improvements in the cumulus expansion area. Sal reduced oocyte levels of reactive oxygen species (ROS) and enhanced intracellular GSH levels. Sal supplementation enhanced the mitochondrial membrane potential (MMP), ATP level, and mtDNA copy number, which shows that Sal enhances the cytoplasmic maturation of oocytes. Oocytes in the Sal group exhibited slowed apoptosis and reduced DNA breakage. Cell cycle signals and oocyte meiosis play important roles in oocyte maturation. The mRNA expressions of the MAPK pathway and MAPK phosphorylation increased significantly in the Sal group. The mRNA expression of the oocyte meiosis gene also increased significantly. These results show that Sal enhances the nuclear maturation of oocytes. Moreover, Sal increased the number of blastocyst cells, the proliferation of blastocysts, and the expressions of pluripotency genes. Sal down-regulated apoptosis-related genes and the apoptotic cell rate of blastocysts. In summary, our results demonstrate that Sal is helpful to improving the quality of porcine oocytes in vitro, and their subsequent embryonic development.


Assuntos
Suplementos Nutricionais , Meiose , Feminino , Gravidez , Animais , Suínos , Desenvolvimento Embrionário , RNA Mensageiro
10.
Cancer Gene Ther ; 30(11): 1498-1512, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37542131

RESUMO

The epidermal growth factor receptor (EGFR) is one of the first and most prominent driver genes known to promote malignant lung cancer. Investigating regulatory mechanisms beyond ligand-receptor binding, phosphorylation, and receptor kinase activation as means of EGFR signaling activation is important for improving EGFR-targeted therapy. Here, we report that Laminin-5γ-2 (LAMC2) retained high oncogenic capacity in lung cancer, silencing LAMC2 inhibited EGFR-induced cell proliferation and tumor growth in vivo. Deletion mutation experiments showed that both the EGF-Lam and LamB regions of LAMC2 are necessary for EGFR receptor binding, and that LAMC2 and EGFR were found to co-localize at the endoplasmic reticulum (ER) membrane. In addition, LAMC2 overexpression enhanced EGFR membrane deposition and promoted EGFR transport from the ER. Moreover, LAMC2 was necessary for preventing EGFR protein degradation via ubiquitination. Lastly, our study showed that high LAMC2 expression is positively associated with response to gefitinib (EGFR tyrosine kinase inhibitor) treatment. Overall, our study revealed a new regulatory mechanism of LAMC2 in promoting EGFR protein expression and stability by facilitating ER transport and preventing protein degradation via ubiquitination. Moreover, LAMC2 may serve as a stratifying biomarker for patients suitable for EGFR-TKI treatment.


Assuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Receptores ErbB/metabolismo , Membrana Celular/metabolismo , Biomarcadores , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Mutação , Linhagem Celular Tumoral , Laminina/genética
11.
J Pain Res ; 16: 2189-2204, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37397275

RESUMO

Background: Over the past decade, acupuncture in the perioperative period has attracted great interest, and a growing number of related literature has been published. Purpose: To analyze the general information and identify the research hotspots and trends of acupuncture in perioperative medicine in the last 10 years by bibliometric analysis. Methods: We searched the Web of Science Core Collection for publications on acupuncture in perioperative medicine from 2013 to 2023. The articles and reviews were collected with no language restriction. CiteSpace and VOSviewer software were used for bibliometric and visual analysis of relevant literature. Results: A total of 814 bibliographic records were retrieved. Overall, the annual number of publications showed an increasing trend. China and its institutions were in a leading position regarding the publication number. With comparatively more scientific collaboration with China, the USA ranked second. Shanghai University of Traditional Chinese Medicine was the most prolific institution. Ha, In-Hyuk had the most publications, and Han JS and Lee A were the most cited authors. Medicine was the most popular journal and Journal of Clinical Oncology had the highest impact factor. "Acupuncture", "electroacupuncture" and "postoperative pain" were the top three keywords. The most popular topics were postoperative pain, postoperative ileus, and postoperative nausea and vomiting according to the keywords and references. And the clusters of postoperative cognitive dysfunction, anxiety, and breast cancer attracted relatively more attention recently. Conclusion: This study summarized the research status, hotspots, and trends of acupuncture in perioperative medicine in the past decade, which may aid researchers in better understanding this field. The research hotspots primarily focused on postoperative pain management and postoperative gastrointestinal function. The research of acupuncture for postoperative cognitive dysfunction, cancer-related surgery, and psychological states were the main frontiers topics and may be the focus in the future.

12.
Macromolecules ; 56(14): 5502-5511, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37521250

RESUMO

Polymorphism of semicrystalline polymers has significant influence on their physical properties, with each form having its advantages and disadvantages. However, real-life polymer processing often results in different coexisting crystal polymorphs, and it remains a challenge to determine their shape, spatial distribution, and volume fraction. Here, i-polypropylene (i-PP) sheets containing both α- and ß-forms were prepared either by adding ß-nucleating agent or by fiber pulling-induced crystallization. By adding a compatible dye that is partially rejected from the growing crystalline aggregates (spherulites and cylindrites), we visualize the shape of these objects in 3D using two-photon fluorescence confocal microscopy. To distinguish between crystal forms, we take advantage of the difference in dye-retaining ability of the α- and ß-aggregates. Even in 2D, fluorescence microscopy (FM) distinguishes the two crystal forms better than polarized microscopy. In 3D imaging, the volume fraction and spatial distribution of α- and ß-forms in different morphological types could be determined quantitatively. Morphologies described as α-teeth, ß-fans, and α-teardrops were visualized for the first time in 3D. Furthermore, internal and surface microcracks were seen to be associated predominantly with the ß-form and around the fiber. Spatial distribution of α- and ß-forms was also determined by scanning with a synchrotron X-ray beam. Good agreement was obtained with 3D microscopy, but XRD could not match the detail obtainable by the tomography. The work demonstrates the ability of the 3D imaging method to distinguish different crystal forms and their specific morphologies.

13.
Viruses ; 15(6)2023 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-37376540

RESUMO

Human adenovirus serotype 31 (HAdV-31) is closely associated with gastroenteritis in children and can cause fatal systemic disseminated diseases in immunocompromised patients. The lack of genomic data for HAdV-31, especially in China, will greatly limit research on its prevention and control. Sequencing and bioinformatics analyses were performed for HAdV-31 strains from diarrheal children in Beijing, China, during 2010-2022. Three capsid protein genes (hexon, penton, and fiber) were obtained in 37 cases, including one in which the whole genome was sequenced. HAdV-31 strains clustered into three distinct clades (I-III) in a phylogenetic tree constructed based on concatenated genes and the whole genome; the endemic strains only gathered into clade II, and most of the reference strains clustered into clade I. Compared with penton and hexon, fiber had a faster evolutionary rate (1.32 × 10-4 substitutions/site/year), an earlier divergence time (1697), lower homology (98.32-100% at the amino acid level), and greater genetic variation (0.0032). Four out of the six predicted positive selection pressure codons were also in the knob of fiber. These results reveal the molecular evolution characteristics and variations of HAdV-31 in Beijing, and fiber may be one of the main evolution driving forces.


Assuntos
Infecções por Adenovirus Humanos , Adenovírus Humanos , Criança , Humanos , Pequim/epidemiologia , Adenovírus Humanos/genética , Filogenia , Sorogrupo , China/epidemiologia , Evolução Molecular , Análise de Sequência de DNA/métodos , Variação Genética
14.
Front Pediatr ; 11: 1187078, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37360358

RESUMO

Objectives: X-linked adrenoleukodystrophy (ALD) is a peroxisomal disease caused by mutations in the ABCD1 gene. Childhood cerebral ALD (CCALD) is characterized by inflammatory demyelination, rapidly progressing, often fatal. Hematopoietic stem cell transplant only delays disease progression in patients with early-stage cerebral ALD. Based on emergency humanitarianism, this study aims to investigate the safety and efficacy of sirolimus in the treatment of patients with CCALD. Methods: This was a prospective, single-center, one-arm clinical trial. We enrolled patients with CCALD, and all enrolled patients received sirolimus treatment for three months. Adverse events were monitored and recorded to evaluate the safety. The efficacy was evaluated using the neurologic function scale (NFS), Loes score, and white matter hyperintensities. Results: A total of 12 patients were included and all presented with CCALD. Four patients dropped out and a total of eight patients in the advanced stage completed a 3-month follow-up. There were no serious adverse events, and the common adverse events were hypertonia and oral ulcers. After sirolimus treatment, three of the four patients with an initial NFS > 10 showed improvements in their clinical symptoms. Loes scores decreased by 0.5-1 point in two of eight patients and remained unchanged in one patient. Analysis of white matter hyperintensities revealed a significant decrease in signal intensity (n = 7, p = 0.0156). Conclusions: Our study suggested that autophagy inducer sirolimus is safe for CCALD. Sirolimus did not improve clinical symptoms of patients with advanced CCALD significantly. Further study with larger sample size and longer follow-up is needed to confirm the drug efficacy.Clinical Trial registration: https://www.chictr.org.cn/historyversionpuben.aspx, identifier ChiCTR1900021288.

16.
Biosens Bioelectron ; 228: 115193, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-36906988

RESUMO

There is a growing but unmet need for point-of-care detection of prostate-specific antigen (PSA) in body fluid which may facilitate early diagnosis and therapy of prostate cancer in a cost-effective and user-friendly way. Low sensitivity and narrow detection range limits applications of point-of-care testing in practice. Here, an immunosensor is first presented based on shrink polymer and integrated into a miniaturized electrochemical platform for detecting PSA in clinical samples. The sensing electrode was prepared by sputtering a gold film on shrink polymer, followed by heating to shrink the electrode to a small size with wrinkles from nano-scale to micro-scale. These wrinkles can be directly regulated by the thickness of the gold film with high specific areas for enhancement of antigen-antibody binding (3.9 times). A distinct difference between electrochemical active surface area (EASA) and response to PSA of shrink electrodes was observed and discussed. The electrode was treated with air plasma and modified with self-assembled graphene to further enhance the sensor's sensitivity (10.4 times). The shrink sensor with gold 200 nm thick integrated into the portable system was validated by a label-free immunoassay for detection of PSA in 20 µL serum within 35 mins. It exhibited a limit of detection of 0.38 fg/mL, the lowest among label-free PSA sensors, and a wide linear response from 10 fg/mL to 1000 ng/mL. Moreover, the sensor demonstrated reliable assay results in clinical serums, comparable to the commercial chemiluminescence instrument, confirming its feasibility for clinical diagnosis.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Masculino , Humanos , Antígeno Prostático Específico , Polímeros , Sistemas Automatizados de Assistência Junto ao Leito , Técnicas Biossensoriais/métodos , Imunoensaio/métodos , Eletrodos , Ouro , Técnicas Eletroquímicas/métodos , Limite de Detecção
17.
Macromol Biosci ; 23(4): e2200502, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36637816

RESUMO

The regeneration strategy for bone defects is greatly limited by the bone microenvironment, and excessive reactive oxygen species (ROS) seriously hinder the formation of new bone. Reduced graphene oxide (rGO) is expected to meet the requirements because of its ability to scavenge free radicals through electron transfer. Antioxidant hydrogels based on gelatine methacrylate (GM), acrylyl-ß-cyclodextrin (Ac-CD), and rGO functionalized with ß-cyclodextrin (ß-CD) are developed for skull defect regeneration, but the mechanism of how rGO-based hydrogels enhance bone repair remains unclear. In this work, it is confirmed that the GM/Ac-CD/rGO hydrogel has good antioxidant capacity, and promotes osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and angiogenesis of human umbilical vein endothelial cells (HUVECs). The rGO-based hydrogel affects ZEB1/Notch1 to promote tube formation. Furthermore, two-photon laser scanning microscopy is used to observe the ROS in a skull defect. The rGO-based hydrogel promotes type H vessel formation in a skull defect. In conclusion, the hydrogel neutralizes ROS in the vicinity of a skull defect and stimulates ZEB1/Notch1 to promote the coupling of osteogenesis and angiogenesis, which may be a possible approach for bone regeneration.


Assuntos
Grafite , Osteogênese , Humanos , Grafite/farmacologia , Espécies Reativas de Oxigênio , Hidrogéis/farmacologia , Antioxidantes , Regeneração Óssea , Diferenciação Celular , Células Endoteliais da Veia Umbilical Humana , Gelatina/farmacologia , Homeobox 1 de Ligação a E-box em Dedo de Zinco , Receptor Notch1
18.
Virol J ; 20(1): 4, 2023 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-36624458

RESUMO

BACKGROUND: Under the pressure of non-pharmaceutical interventions (NPIs) targeting severe acute respiratory syndrome coronavirus 2, the prevalence of human adenovirus (HAdV) was monitored before and after NPIs launched on Jan 24, 2020 in pediatric patients in Beijing, China. METHODS: Respiratory samples collected from children hospitalized with acute respiratory infections from Jan 2015 to Dec 2021 were screened by direct immunofluorescence test or capillary electrophoresis-based multiplex PCR assay. The hexon, penton base, and fiber genes were amplified from HAdV positive specimens, then sequenced. For HAdV typing, phylogenetic trees were built by MEGA X. Then clinical data of HAdV positive cases were collected. All data were evaluated using SPSS Statistics 22.0 software. RESULTS: A total of 16,097 children were enrolled and 466 (2.89%, 466/16,097) were HAdV-positive. The positive rates of HAdV varied, ranging from 4.39% (151/3,438) in 2018 to1.25% (26/2,081) in 2021, dropped from 3.19% (428/13,408) to 1.41% (38/2,689) from before to after NPIs launched (P < 0.001). There were 350 cases typed into nine types of species B, C, or E and 34 recorded as undetermined. Among them, HAdV-B3 (51.56%, 198/384) was the most prevalent types from 2015 to 2017, and HAdV-B7 (29.17%, 112/384) co-circulated with HAdV-B3 from 2018 to 2019. After NPIs launched, HAdV-B3 and B7 decreased sharply with HAdV-B7 undetected in 2021, while HAdV-C1 became the dominant one and the undetermined were more. CONCLUSIONS: The endemic pattern of HAdV changed in Beijing because of the NPIs launched for COVID-19. Especially, the dominant types changed from HAdV-B to HAdV-C.


Assuntos
Infecções por Adenovirus Humanos , Adenovírus Humanos , COVID-19 , Infecções Respiratórias , Criança , Humanos , Pequim/epidemiologia , Adenovírus Humanos/genética , Filogenia , Infecções por Adenovirus Humanos/epidemiologia , Infecções por Adenovirus Humanos/prevenção & controle , COVID-19/epidemiologia , COVID-19/prevenção & controle , China/epidemiologia , Infecções Respiratórias/epidemiologia , Reação em Cadeia da Polimerase Multiplex
20.
Front Physiol ; 14: 1306453, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38187137

RESUMO

Background: Accurate estimation of perioperative blood transfusion risk in lumbar posterior interbody fusion is essential to reduce the number, cost, and complications associated with blood transfusions. Machine learning algorithms have the potential to outperform traditional prediction methods in predicting perioperative blood transfusion. This study aimed to construct a machine learning-based perioperative transfusion risk prediction model for lumbar posterior interbody fusion in order to improve the efficacy of surgical decision-making. Methods: We retrospectively collected clinical data on 1905 patients who underwent lumbar posterior interbody fusion surgery at the Second Hospital of Shanxi Medical University between January 2021 and March 2023. All the data was randomly divided into a training set and a validation set, and the "feature_importances" method provided by eXtreme Gradient Boosting (XGBoost) algorithm was applied to select statistically significant features on the training set to establish five machine learning prediction models. The optimal model was identified by utilizing the area under the curve (AUC) and the probability calibration curve on the validation set. Shapley additive explanations (SHAP) and local interpretable model-agnostic explanations (LIME) were employed for interpretable analysis of the optimal model. Results: In the postoperative outcomes of patients, the number of hospital days in the transfusion group was longer than that in the non-transfusion group. Additionally, the transfusion group experienced higher total hospital costs, 90-day readmission rates, and complication rates within 90 days after surgery than the non-transfusion group. A total of 9 features were selected for the models. The XGBoost model performed best with an AUC value of 0.958. The SHAP values showed that intraoperative blood loss, intraoperative fluid infusion, and number of fused segments were the top 3 most important features affecting perioperative blood transfusion in lumbar posterior interbody fusion. The LIME algorithm was used to interpret the individualized prediction. Conclusion: Surgery, ASA class, levels fused, total intraoperative blood loss, operative time, and preoperative Hb are viable predictors of perioperative blood transfusion in lumbar posterior interbody fusion. The XGBoost model has demonstrated superior predictive efficacy compared to the traditional logistic regression model, making it a more effective decision-making tool for perioperative blood transfusion.

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