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1.
Phys Rev Lett ; 132(13): 131401, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38613266

RESUMO

We present a framework to compute amplitudes for the gravitational analog of the Raman process, a quasielastic scattering of waves off compact objects, in worldline effective field theory. As an example, we calculate third post-Minkowskian order [O(G^{3})], or two-loop, phase shifts for the scattering of a massless scalar field including all tidal effects and dissipation. Our calculation unveils two sources of the classical renormalization-group flow of dynamical Love numbers: a universal running independent of the nature of the compact object, and a running self-induced by tides. Restricting to the black hole case, we find that our effective field theory phase shifts agree exactly with those from general relativity, provided that the relevant static Love numbers are set to zero. In addition, we carry out a complete matching of the leading scalar dynamical Love number required to renormalize a universal short scale divergence in the S wave. Our results pave the way for systematic calculations of gravitational Raman scattering at higher post-Minkowskian orders.

2.
J Burn Care Res ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38477626

RESUMO

Hypertrophic scar development is a complication associated with wound healing, impacting local appearance and function. The type I/III collagen ratio affects the extent of hypertrophic scarring; a reduced ratio can ameliorate this. In this study, recombinant human collagen type III was developed. Liquid chromatography-tandem mass spectrometry was used to determine its amino acid sequence and confirm its high level of homology with natural human type III collagen. Recombinant human collagen type III displayed no cytotoxicity and did not confer skin irritation and sensitization. Immunofluorescence and western blot analyses of histidine following incubation with fibroblasts suggested cell entry of recombinant human collagen type III. Furthermore, recombinant human collagen type III promoted the synthesis of the natural type III collagen in fibroblasts, resulting in a more obvious increase of type III collagen content in fibroblasts than that of type I collagen, and then decreased the ratio of type I/III collagen. The results of 5-ethynyl-2'-deoxyuridine staining assay suggested enhanced fibroblast proliferation. Following local injection of recombinant human collagen type III, rabbit ear scarring was significantly reduced after 60 days. Vancouver Scar Scale evaluation showed that all index scores were significantly reduced. Western blotting and Picro-Sirius red staining showed that the natural type III collagen increase in scar tissue was greater than that of type I collagen, decreasing the type I/III ratio. In summary, recombinant human collagen type III can be taken up by fibroblasts and promote natural collagen synthesis-especially that of type III-thereby reducing the type I/III ratio and improving hypertrophic scarring.

3.
Res Social Adm Pharm ; 20(6): 65-71, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38423928

RESUMO

BACKGROUND: During the ongoing global pandemic of COVID-19, the association between hyperglycemia and COVID-19 infection has emerged as a notable concern. Therefore, finding effective methods to manage hyperglycemia in patients with COVID-19 is crucial. OBJECTIVE: To introduce the clinical pharmacists participating in multidisciplinary collaborative whole hospital blood glucose management mode, and to explore its effect on blood glucose control in patients with coronavirus disease 2019 infection and complicated with hyperglycemia. METHODS: Patients with COVID-19 treated at Nanjing Drum Tower Hospital from December 2022 to January 2023 were assigned to routine diagnosis and treatment group and whole hospital blood glucose management group according to the blood glucose management plan received by patients. The groups were compared in regards to their adherence to management advice, blood glucose levels, fluctuation, inflammation-related indicators, medical service-related indicators, and incidence of hypoglycemia and adverse events. RESULTS: After 5 days of glucose management, both groups showed a decrease in fasting and postprandial blood glucose. Postprandial blood glucose in the whole hospital glucose management group was significantly lower than the routine group (P < 0.05). The whole hospital glucose management group showed a significant increase in compliance rate, improved inflammation-related indicators, and higher detection rates for hemoglobin and islet function (P < 0.05). Implementation rates for medical orders and treatment plans were also higher in the whole hospital group (P < 0.05). There was no significant difference in incidence of adverse events. CONCLUSIONS: Multidisciplinary blood glucose management is highly recommended for patients with COVID-19 who have hyperglycemia due to its effectiveness, standardization, safety, and improvement of inflammation indicators.


Assuntos
Glicemia , COVID-19 , Hiperglicemia , Farmacêuticos , Papel Profissional , Humanos , COVID-19/complicações , Hiperglicemia/sangue , Hiperglicemia/tratamento farmacológico , Farmacêuticos/organização & administração , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Serviço de Farmácia Hospitalar/organização & administração , Equipe de Assistência ao Paciente/organização & administração , Controle Glicêmico , Hipoglicemia , Adulto
4.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 45(4): 597-607, 2023 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-37654140

RESUMO

Objective To screen out the potential prediction genes for nasopharyngeal carcinoma(NPC)from the gene microarray data of NPC samples and then verify the genes by cell experiments.Methods The NPC dataset was downloaded from Gene Expression Omnibus,and limma package was employed to screen out the differentially expressed genes.Weighted correlation network analysis package was used for weighted gene co-expression network analysis,and Venn diagram was drawn to find the common genes.The gene ontology annotation and Kyoto encyclopedia of genes and genomes pathway enrichment were then performed for the common genes.The biomarkers for NPC were further explored by protein-protein interaction network,LASSO regression,and non-parametric tests.Real-time quantitative PCR and Western blotting were employed to determine the mRNA and protein levels of key predictors of NPC,so as to verify the screening results.Results There were 622 up-regulated genes and 351 down-regulated genes in the GSE12452 dataset.A total of 116 common genes were obtained by limma analysis and weighted gene co-expression network analysis.The common genes were mainly involved in the biological processes of cell proliferation and regulation and regulation of intercellular adhesion.They were mainly enriched in Rap1,Ras,and tumor necrosis factor signaling pathways.Six key genes were screened out,encoding angiopoietin-2(ANGPT2),dual oxidase 2(DUOX2),coagulation factor Ⅲ(F3),interleukin-15(IL-15),lipocalin-2,and retinoic acid receptor-related orphan receptor B(RORB).Real-time quantitative PCR and Western blotting showed that the NPC cells had up-regulated mRNA and protein levels of ANGPT2 and IL-15 and down-regulated mRNA and protein levels of DUOX2,F3,and RORB,which was consistent with the results predicted by bioinformatics.Conclusion ANGPT2,DUOX2,F3,IL-15 and RORB are potential predictive molecular markers and therapeutic targets for NPC,which may be involved in Rap1,Ras,tumor necrosis factor and other signaling pathways.


Assuntos
Interleucina-15 , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/genética , Oxidases Duais , Biologia Computacional , Neoplasias Nasofaríngeas/genética
5.
Sci Adv ; 9(34): eadg6693, 2023 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-37611092

RESUMO

MYCN amplification (MNA) is a defining feature of high-risk neuroblastoma (NB) and predicts poor prognosis. However, whether genes within or in close proximity to the MYCN amplicon also contribute to MNA+ NB remains poorly understood. Here, we identify that GREB1, a transcription factor encoding gene neighboring the MYCN locus, is frequently coexpressed with MYCN and promotes cell survival in MNA+ NB. GREB1 controls gene expression independently of MYCN, among which we uncover myosin 1B (MYO1B) as being highly expressed in MNA+ NB and, using a chick chorioallantoic membrane (CAM) model, as a crucial regulator of invasion and metastasis. Global secretome and proteome profiling further delineates MYO1B in regulating secretome reprogramming in MNA+ NB cells, and the cytokine MIF as an important pro-invasive and pro-metastatic mediator of MYO1B activity. Together, we have identified a putative GREB1-MYO1B-MIF axis as an unconventional mechanism promoting aggressive behavior in MNA+ NB and independently of MYCN.


Assuntos
Neuroblastoma , Secretoma , Humanos , Proteína Proto-Oncogênica N-Myc/genética , Neuroblastoma/genética , Agressão , Sobrevivência Celular
6.
Clin Neurol Neurosurg ; 233: 107935, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37573678

RESUMO

PURPOSE: To stratify angiographic images of chronic internal carotid artery occlusion (CICAO) into a newly modified angiographic classification, and identify suitable candidates for endovascular recanalization. METHODS: This study included 51 consecutive patients with symptomatic CICAO who underwent endovascular recanalization at our institution. Patients' clinical information, angiographic findings, procedural results, and outcomes were recorded. We attempted to stratify all angiographic images into categories based on morphological occlusive patterns and distal internal carotid artery (ICA) lumen reconstitution on digital subtraction angiography (DSA). RESULTS: Four types (I-IV) of CICAO were identified based on angiographic characteristics. We defined type I as having a tapered (IA) or blunt stump (IB) and distal ICA lumen reconstitution with collateral filling; type II as having no stump but with distal ICA lumen reconstitution; type III as having a tapered (IIIA) or blunt stump (IIIB) but no distal ICA lumen reconstitution; type IV as having no stump and no distal ICA lumen reconstitution. The rate of successful recanalization was 90.3 % for type I, 60.0 % for type II, 50.0 % for type III, 0 % for type IV, respectively (P = 0.002). The overall intraoperative complication rate was 11.8 %, and none of them led to severe neurological damage or death. The follow-up modified Rankin Scale (mRS) scores were significantly decreased in successfully revascularized patients, whilst there were no significant changes in the other failed patients. CONCLUSION: For symptomatic CICAO, our newly modified angiographic classification may be comprehensive and useful in selecting suitable patients for recanalization and grading the difficulty of the procedures.


Assuntos
Doenças das Artérias Carótidas , Procedimentos Endovasculares , Humanos , Artéria Carótida Interna/diagnóstico por imagem , Artéria Carótida Interna/cirurgia , Resultado do Tratamento , Doenças das Artérias Carótidas/complicações , Angiografia Digital , Procedimentos Endovasculares/métodos , Estudos Retrospectivos
7.
Eur Radiol ; 33(12): 9130-9138, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37498384

RESUMO

OBJECTIVE: To compare the prognostic value of net water uptake (NWU) and target mismatch (TM) on CT perfusion (CTP) in acute ischemic stroke (AIS) patients with late time window. METHODS: One hundred and nine consecutive AIS patients with anterior-circulation large vessel occlusion presenting within 6-24 h from onset/last seen well were enrolled. Automated Alberta Stroke Program Early CT Score-based NWU (ASPECTS-NWU) was calculated from admission CT. The correlation between ASPECTS-NWU and CTP parameters was assessed. Predictors for favorable outcome (modified Rankin Scale score ≤ 2) at 90 days were assessed using logistic regression analysis. The ability of outcome prediction between ASPECTS-NWU and TM (an ischemic core < 70 mL, a mismatch ratio ≥ 1.8, and an absolute difference ≥ 15 mL) was compared using receiver operating characteristic (ROC) curve. RESULTS: A higher level of ASPECTS-NWU was associated with a larger ischemic core (r = 0.66, p < 0.001) and a larger hypoperfusion volume (r = 0.38, p < 0.001). ASPECTS-NWU performed better than TM for outcome stratification (area under the curve [AUC], 0.738 vs 0.583, p = 0.004) and was the only independent neuroimaging marker associated with favorable outcomes compared with CTP parameters (odds ratio, 0.73; 95% confidence interval [CI] 0.62-0.87, p < 0.001). An outcome prediction model including ASPECTS-NWU and clinical variables (National Institutes of Health Stroke Scale scores and age) yielded an AUC of 0.828 (95% CI 0.744-0.893; sensitivity 65.4%; specificity 87.7%). CONCLUSION: ASPECTS-NWU performed better than TM for outcome prediction in AIS patients with late time window and might be an alternative imaging biomarker to CTP for patient selection. CLINICAL RELEVANCE STATEMENT: Automated Alberta Stroke Program Early CT Score-based net water uptake outperforms target mismatch on CT perfusion for the outcome prediction in patients with acute ischemic stroke and can be an alternative imaging biomarker for patient selection in late therapeutic window. KEY POINTS: • A higher ASPECTS-based net water uptake was associated with larger ischemic cores and hypoperfusion volumes on CT perfusion. • ASPECTS-based net water uptake outperformed target mismatch for outcome prediction in acute ischemic stroke with extended therapeutic window. • ASPECTS-based net water uptake can be an alternative biomarker to target mismatch for selecting acute ischemic stroke patients with late therapeutic window.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/terapia , Água , Tomografia Computadorizada por Raios X/métodos , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Prognóstico , Biomarcadores , Resultado do Tratamento , Trombectomia
8.
J Comput Assist Tomogr ; 47(4): 671-676, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37365699

RESUMO

OBJECTIVE: To investigate whether truncal-type occlusion based on multiphase computed tomographic angiography (mpCTA) was more effective for predicting intracranial atherosclerotic stenosis-related occlusion (ICAS-O) than occlusion type based on single-phase computed tomographic angiography (spCTA) in patients with acute ischemic stroke with large-vessel occlusion (AIS-LVO) in the middle cerebral artery (MCA). METHODS: Data were retrospectively collected from 72 patients with AIS-LVO in the MCA between January 2018 and December 2019. The occlusion types included truncal-type and branching-site occlusions. The association between ICAS-O and occlusion type based on the 2 computed tomographic angiography patterns was analyzed, and receiver operating characteristic curves were plotted for assessment. The areas under the curve were compared to determine the difference between the predictive powers of truncal-type occlusion based on mpCTA and spCTA. RESULTS: Among the 72 patients, 16 were classified as having ICAS-O and 56 as having embolisms. In univariate analysis, truncal-type occlusion was significantly associated with ICAS-O ( P < 0.001 for mpCTA and P = 0.001 for spCTA). After multivariable analysis, truncal-type occlusion based on both mpCTA and spCTA remained independently associated with ICAS-O ( P = 0.002 for mpCTA and P = 0.029 for spCTA). The areas under the curve were 0.821 for mpCTA and 0.683 for spCTA; this difference was statistically significant ( P = 0.024). CONCLUSIONS: In patients with AIS-LVO in the MCA, truncal-type occlusion based on mpCTA enables more accurate detection of ICAS-O than that based on spCTA.


Assuntos
Arteriosclerose Intracraniana , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Acidente Vascular Cerebral/complicações , Estudos Retrospectivos , Constrição Patológica/diagnóstico por imagem , Constrição Patológica/complicações , Angiografia Cerebral/métodos , Arteriosclerose Intracraniana/complicações , Arteriosclerose Intracraniana/diagnóstico por imagem , Artéria Cerebral Média/diagnóstico por imagem
9.
Eur Radiol ; 33(3): 1792-1800, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36282310

RESUMO

OBJECTIVES: To assess the predictors of ghost infarct core (GIC) in stroke patients achieving successful recanalization after mechanical thrombectomy (MT), based on final infarct volume (FIV) calculated from follow-up diffusion-weighted imaging (DWI). METHODS: A total of 115 consecutive stroke patients who had undergone baseline computed tomography perfusion (CTP) scan, achieved successful recanalization after MT, and finished follow-up DWI evaluation were retrospectively enrolled. Ischemic core volume was automatically generated from baseline CTP, and FIV was determined manually based on follow-up DWI. Stroke-related risk factors and demographic, clinical, imaging, and procedural data were collected and assessed. Univariate and multivariate analyses were applied to identify the predictors of GIC. RESULTS: Of the 115 included patients (31 women and 84 men; median age, 66 years), 18 patients (15.7%) showed a GIC. The GIC group showed significantly shorter time interval from stroke onset to CTP scan and that from stroke onset to recanalization (both p < 0.001), but higher ischemic core volume (p < 0.001), hypoperfused area volume (p < 0.001), mismatch area volume (p = 0.006), and hypoperfusion ratio (p = 0.001) than the no-GIC group. In multivariate analysis, time interval from stroke onset to CTP scan (odds ratio [OR], 0.983; p = 0.005) and ischemic core volume (OR, 1.073; p < 0.001) were independently associated with the occurrence of GIC. CONCLUSIONS: In stroke patients achieving successful recanalization after MT, time interval from stroke onset to CTP and ischemic core volume are associated with the occurrence of GIC. Patients cannot be excluded from MT solely based on baseline CTP-derived ischemic core volume, especially for patients with a shorter onset time. KEY POINTS: • Ghost infarct core (GIC) was found in 15.7% of patients with acute ischemic stroke (AIS) in our study cohort. • GIC was associated with stroke onset time, volumetric parameters derived from CTP, and collateral status indicated by HIR. • Time interval from stroke onset to CTP scan and ischemic core volume were independent predictors of GIC.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Masculino , Humanos , Feminino , Idoso , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/cirurgia , Estudos Retrospectivos , Imagem de Perfusão/métodos , Tomografia Computadorizada por Raios X/métodos , Trombectomia/métodos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Infarto , Perfusão , Resultado do Tratamento
10.
Acta Radiol ; 64(3): 1139-1147, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35575229

RESUMO

BACKGROUND: Intracranial atherosclerosis-related large vessel occlusion (ICAS+LVO) poses an important technical challenge for endovascular thrombectomy (EVT). PURPOSE: To evaluate the value of D-dimer in predicting ICAS+LVO alone and in combination with other clinical and imaging predictors. MATERIAL AND METHODS: Consecutive patients who underwent EVT at our center between January 2018 and June 2021 were retrospectively reviewed. Patients were classified to the ICAS+LVO or ICAS-LVO group according to angiographic findings. Collateral gradings were evaluated based on computed tomography angiography and categorized as follows: score 0-1 unfavorable collaterals and score 2-3 favorable collaterals. Receiver operating characteristic curve was analyzed to evaluate the predictive value of D-dimer and the combination of other predictors for ICAS+LVO. RESULTS: A total of 374 patients were enrolled, among them, 107 (28.6%) had an ICAS+LVO, while ICAS-LVO was determined in 267 (71.4%) patients. Median D-dimer levels were lower (0.36 vs. 1.18 mg/L; P < 0.001) while the proportion of favorable collaterals was higher (85.0% vs. 22.5%; P < 0.001) in the ICAS+LVO group than the ICAS-LVO group. After multivariable analysis, D-dimer (adjusted odds ratio [OR]=0.32, 95% confidence interval [CI]=0.21-0.50; P < 0.001) and collaterals (adjusted OR=16.25, 95% CI=7.58-34.84; P < 0.001) remained independent predictors of ICAS+LVO. The area under the curve of D-dimer, collaterals, and combination for identification of ICAS+LVO was 0.82, 0.85, and 0.92, respectively. CONCLUSION: Low early plasma D-dimer levels are a significant and independent predictor of ICAS+LVO, and predictive value strengthens when in a combined model using D-dimer and collateral grading.


Assuntos
Arteriosclerose Intracraniana , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/diagnóstico por imagem , Estudos Retrospectivos , Trombectomia/métodos , Acidente Vascular Cerebral/diagnóstico por imagem
11.
Neuroradiology ; 65(1): 105-111, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35925438

RESUMO

PURPOSE: To evaluate the feasibility of using CT perfusion (CTP) with increased temporal sampling interval to predict the target mismatch status in acute ischemic stroke (AIS) patients with anterior circular large-vessel occlusion (LVO). METHODS: CTP with a sampling interval of 1.7 s (CTP1.7 s) was scanned in 77 AIS patients for pre-treatment evaluation. Simulated CTP data with sampling interval of 3.4 s (CTP3.4 s) or 5.1 s (CTP5.1 s) were reconstructed, respectively. Target mismatch was defined according to the EXTEND-IA (Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial) and DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) trial criteria, respectively. Pearson correlation analysis, Mann-Whitney U test, Bland-Altman analysis, and chi-square test were used for statistical analysis as appropriate. RESULTS: Significant correlations were found on the volume of ischemic core, hypo-perfused area, mismatch area, and ratio between CTP1.7 s and CTP3.4 s or CTP5.1 s (all p < 0.001). There was no significant difference on the volume of ischemic core, hypo-perfused area, mismatch area, and mismatch ratio between CTP1.7 s and CTP3.4 s or CTP5.1 s (all p > 0.05). Compared with CTP1.7 s, CTP3.4 s or CTP5.1 s showed comparable performance in predicting the target mismatch status in the AIS patients with LVO (both p > 0.05). CONCLUSIONS: CTPs with increased temporal sampling intervals that lead to reduced radiation doses are feasible and may provide comparable performance in predicting target mismatch status in AIS patients with LVO.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/terapia , Perfusão , Imagem de Perfusão/métodos , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Tomografia Computadorizada por Raios X/métodos
12.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-998173

RESUMO

ObjectiveTo evaluate the clinical efficacy and adverse effects of Shugan Hewei prescription combined with vonoprazan in the treatment of refractory gastroesophageal reflux disease (RGERD) due to qi depression and phlegm obstruction. MethodEighty RGERD patients who met the inclusion criteria underwent 24-hour pH impedance and high-resolution esophageal manometry and electronic gastroscopy. The 80 patients were randomly assigned to an observation group (Shugan Hewei prescription, one bag each time, twice a day + vonoprazan, 20 mg each time, once a day) and a control group (vonoprazan, 20 mg each time, once a day) by the random number table method. The treatment in both groups lasted for 4 weeks. The clinical efficacy was examined. The scores of TCM symptoms (pharyngeal discomforts such as phlegm obstruction, retrosternal discomfort, and belching), somatic symptoms, quality of life, and improvement of esophageal mucosa under gastroscopy were observed in both groups before treatment and after treatment for 2 and 4 weeks. ResultSeventy-five patients completed the trial were included in this study, including 38 patients in the observation group and 37 patients in the control group. The total response rate in the observation group was 89.47%(34/38), which was higher than that (62.16%,23/37) in the control group (χ2=13.014, P<0.01). After treatment, the scores of esophageal mucous membrane, reflux disease symptoms, TCM symptoms, gastroesophageal reflux disease health-related quality of life scale (GERD-HRQL), and somatic self-rating scale (SSS) decreased in both groups(P<0.05). Moreover, the observation group outperformed the control group in alleviating heartburn, acid reflux, throat discomforts, midnight coughing, nausea and dry vomiting, mucousy mouth, and insomnia in the patients with GERD (P<0.05,P<0.01). However, the two groups showed no statistically significant differences in the improvement of esophageal mucosa after treatment. ConclusionThe combination of Shugan Hewei prescription with vonoprazan was superior to vonoprazan alone in treating RGERD regarding clinical symptoms, physical signs, quality of life, and somatic symptoms, without causing obvious adverse effects.

13.
Acta Pharmaceutica Sinica ; (12): 320-329, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-965719

RESUMO

Developmental changes in children can affect drug disposition and clinical effects. A physiologically-based pharmacokinetic (PBPK) model is a mathematical model that can be used to predict blood drug concentrations in children and gain insight into age-dependent physiological differences in drug disposition impact. Pediatric PBPK (P-PBPK) models have attracted attention over the past decade. With the concerted efforts of academia, pharmaceutical companies, and regulatory agencies, there are more and more examples of pediatric clinical studies using PBPK models. Nevertheless, the number of P-PBPK models and their predictive performance still lag behind adult models. By referring to the literature, we study the process of children adapting to adult absorption, distribution, metabolism, and excretion (ADME) parameters and analyze the general principles of P-PBPK model establishment. In addition, we summarize the functions and application examples of commonly used P-PBPK modeling software to provide a basis for the rational application of modeling software.

14.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-981434

RESUMO

This study aims to investigate the role of slient mating-type information regulation 2 homolog 1(SIRT1)/tuberous sclerosis complex 2(TSC2)/mammalian target of rapamycin(mTOR) signaling pathways in the Periplaneta americana extract CⅡ-3-induced senescence of human leukemia K562 cells. K562 cells were cultured in vitro and treated with 0(control), 5, 10, 20, 40, 80, and 160 μg·mL~(-1) of P. americana extract CⅡ-3. Cell counting kit-8(CCK-8) and flow cytometry were employed to examine the proliferation and cell cycle of the K562 cells. Senescence-associated β-galactosidase stain kit(SA-β-gal) was used to detect the positive rate of senescent cells. Mitochondrial membrane potential was detected by flow cytometry. The relative mRNA level of telomerase reverse transcriptase(TERT) was determined by fluorescence quantitative PCR. The mRNA and protein levels of SIRT1, TSC2, and mTOR were determined by fluorescence quantitative PCR and Western blot, respectively. The results showed that CⅡ-3 significantly inhibited the proliferation of K562 cells and the treatment with 80 μg·mL~(-1) CⅡ-3 for 72 h had the highest inhibition rate. Therefore, 80 μg·mL~(-1) CⅡ-3 treatment for 72 h was selected as the standard for subsequent experiments. Compared with the control group, CⅡ-3 increased the proportion of cells arrested in G_0/G_1 phase, decreased the proportion of cells in S phase, increased the positive rate of SA-β-Gal staining, elevated the mitochondrial membrane potential and down-regulated the mRNA expression of TERT. Furthermore, the mRNA expression of SIRT1 and TSC2 was down-regulated, while the mRNA expression of mTOR was up-regulated. The protein expression of SIRT1 and p-TSC2 was down-regulated, while the protein expression of p-mTOR was up-regulated. The results indicated that P. americana extract CⅡ-3 induced the senescence of K562 cells via the SIRT1/mTOR signaling pathway.


Assuntos
Humanos , Animais , Periplaneta , Sirtuína 1/genética , Células K562 , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , RNA Mensageiro , Mamíferos
15.
Digital Chinese Medicine ; (4): 357-368, 2023.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-997738

RESUMO

@#,Objective To analyze the current status and development trends of the patents of spleen-invigorating health food with the homology of medicine and food in China, and to provide ideas and references for the research and development of traditional Chinese medicine (TCM) spleen-invigorating health food with the homology of medicine and food. @*Methods@#The State Administration for Market Regulation website’s “Special Food Information Query Platform” and the incoPat global patent database were searched in this study. Based on the methods of bibliometrics, the registered health food and patents related to spleen-invigorating health food with the homology of medicine and food in China were sorted out. Furthermore, the research and development numbers, provinces, institutions, technology and efficacy classification, major drugs, active ingredients and others of invigorating spleen health food in China were analyzed, and filtered patent data were visualized and analyzed by R programming language and CytoScape software. @*Results@# A total of 285 patents of health food with the homology of medicine and food for invigorating spleen were included and analyzed. From 2012, the patent registration numbers of these spleen-invigorating health food with the homology of medicine and food increased significantly in China. Over the past 20 years, the top five provinces in terms of patent disclosures were Guangdong, Anhui, Jiangsu, Shandong, and Guangxi. It was found that the technical efficacy of over 20 patents was described as “immune enhancement” “digestion” “disease prevention”, etc. Patent applications were mainly aimed at the research and development of the preservation of food or ingredients, the specific therapeutic activity of compounds, and pharmaceutical preparations, which were led by corporation research and development registrations, and supplemented by applications from research institutions and individuals. Among the 285 patents, the top 10 raw materials of spleen-invigorating health food with the homology of medicine and food were Shanyao (Dioscoreae Rhizoma), Fuling (Poria), Shanzha (Crataegi Fructus), Baizhu (Atractylodis Macrocephalae Rhizoma), Chenpi (Citri Reticulatae Pericarpium), Dazao (Jujubae Fructus), Gancao (Glycyrrhizae Radix et Rhizoma), Fengmi (Mel), Maiya (Hordei Fructus Germinatus), and Dangshen (Salviae Miltiorrhizae Radix et Rhizoma). The main functions were to nourish spleen and replenish Qi, invigorate spleen and benefit lungs, nourish blood and promote fluid production, and nourish spleen and stomach. @*Conclusion@#The main drug composition and functional components of spleen-invigorating health food with the homology of medicine and food are relatively clear, and the technical effects of invigorating the spleen and stomach, eliminating accumulation of food, and enhancing immunity are highly targeted. This paper provides evidence for the research and development, mechanism research, and process improvement of spleen-invigorating health food with the homology of medicine and food in the future.

16.
Chinese Journal of Trauma ; (12): 10-22, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-992568

RESUMO

Bone defects caused by different causes such as trauma, severe bone infection and other factors are common in clinic and difficult to treat. Usually, bone substitutes are required for repair. Current bone grafting materials used clinically include autologous bones, allogeneic bones, xenografts, and synthetic materials, etc. Other than autologous bones, the major hurdles of rest bone grafts have various degrees of poor biological activity and lack of active ingredients to provide osteogenic impetus. Bone marrow contains various components such as stem cells and bioactive factors, which are contributive to osteogenesis. In response, the technique of bone marrow enrichment, based on the efficient utilization of components within bone marrow, has been risen, aiming to extract osteogenic cells and factors from bone marrow of patients and incorporate them into 3D scaffolds for fabricating bone grafts with high osteoinductivity. However, the scientific guidance and application specification are lacked with regard to the clinical scope, approach, safety and effectiveness. In this context, under the organization of Chinese Orthopedic Association, the Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair ( version 2023) is formulated based on the evidence-based medicine. The consensus covers the topics of the characteristics, range of application, safety and application notes of the technique of autologous bone marrow enrichment and proposes corresponding recommendations, hoping to provide better guidance for clinical practice of the technique.

17.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-991759

RESUMO

Objective:To investigate the compatibility stability of cinepazide maleate injection and dopamine hydrochloride injection and explore the basis for the combined application of cinnamazide maleate injection and dopamine hydrochloride injection.Methods:A method for determining cinnamazide maleate injection and dopamine hydrochloride injection was established using an ultraviolet-visible spectrophotometer and verified from March 1, 2021 to May 20, 2021. The color and pH value of the solution prepared using the two drugs were determined within 5 hours at room temperature. The content change of the prepared solution was determined using an ultraviolet-visible spectrophotometer.Results:The linear range of the mass concentration of cinnamazide maleate was 4.03 - 32.24 mg/L and the linear range of dopamine hydrochloride was 20 -120 mg/L. At 25 ℃, the color of the prepared solution did not change within 5 hours and the pH value was in the range of 4.43 ± 0.06, indicating that the pH of the prepared solution did not change markedly. The concentrations of cinnamazide maleate and dopamine hydrochloride were (98.23 ± 1.09)% and (99.96 ± 0.41)% respectively, indicating good stability.Conclusion:The prepared solution using cinepazide maleate injection and dopamine hydrochloride injection can be used within 5 hours at 25 ℃.

18.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-990315

RESUMO

Objective:To explore the application effect of Assessmen-Diagnosis-Plan-Implementation-Evaluation(ADPIE) teaching model based on skill competition in the teaching of "basic nursing" skills in higher vocational colleges.Methods:This was a quasi experimental study. Convenience sampling method was adopted to select students from two classes of 2021 vocational nursing major of Pingxiang Health Vocational College from February to July 2022 as the research objects, among which 53 nursing students from Class 9 were selected as the experimental group and 55 nursing students from Class 13 were selected as the control group. The experimental group was taught based on the ADPIE teaching mode of skill competition. The control group was taught according to the conventional teaching mode, and the academic record and humanistic care ability of the nursing students in the two groups were compared.Results:The three dimensions of humanistic care ability in experimental group were cognition (70.82 ± 9.20) points, courage (59.58 ± 6.04) points, patience (57.17 ± 5.26) points, total score (187.57 ± 20.50) points. They were higher than those in the control group,which were (67.40 ± 8.83), (55.98 ± 9.03), (54.37 ± 5.96) and (177.75 ± 20.82) points, and there were statistical differences between the groups (t values were 2.61 to 3.42, all P<0.05). In addition, the three dimensions of academic performance: ordinary score (6.10 ± 1.22)points, course score (57.10 ± 6.27) points, objective structured clinical examination (OSCE) score (27.09 ± 2.13)points, total score (90.29 ± 9.69) points, they were also higher than those of the control group (5.06 ± 1.33), (52.73 ± 5.44), (25.35 ± 3.29), and (83.14 ± 10.06), and the differences between groups were statistically significant ( t values were 2.52-3.34, All P<0.05). Conclusions:ADPIE teaching model based on skills competition can improve the course scores and humanistic care ability of nursing students, and the teaching effect is significant.

19.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-989959

RESUMO

Pyroptosis belongs to the programmed cell death of inflammatory cells, which is regulated by GSDMD (Caspase-1,-4,-5-11) and GSDME (Caspase-3, granzyme). Multiple regulatory pathways of pyroptosis are abnormally expressed in gastric cancer cells, indicating that pyroptosis is closely related to gastric cancer and has the potential to become a new target for gastric cancer treatment. Combined with current mainstream treatments such as chemotherapy and immunotherapy, it may improve clinical treatment effect of gastric cancer. This article reviews the molecular mechanism of pyroptosis, the related research on gastric cancer and pyroptosis, and the related research on pyroptosis and gastric cancer treatment to explore the possibility of pyroptosis as a new target for gastric cancer, and to provide new research ideas for gastric cancer treatment.

20.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1008107

RESUMO

Objective To screen out the potential prediction genes for nasopharyngeal carcinoma(NPC)from the gene microarray data of NPC samples and then verify the genes by cell experiments.Methods The NPC dataset was downloaded from Gene Expression Omnibus,and limma package was employed to screen out the differentially expressed genes.Weighted correlation network analysis package was used for weighted gene co-expression network analysis,and Venn diagram was drawn to find the common genes.The gene ontology annotation and Kyoto encyclopedia of genes and genomes pathway enrichment were then performed for the common genes.The biomarkers for NPC were further explored by protein-protein interaction network,LASSO regression,and non-parametric tests.Real-time quantitative PCR and Western blotting were employed to determine the mRNA and protein levels of key predictors of NPC,so as to verify the screening results.Results There were 622 up-regulated genes and 351 down-regulated genes in the GSE12452 dataset.A total of 116 common genes were obtained by limma analysis and weighted gene co-expression network analysis.The common genes were mainly involved in the biological processes of cell proliferation and regulation and regulation of intercellular adhesion.They were mainly enriched in Rap1,Ras,and tumor necrosis factor signaling pathways.Six key genes were screened out,encoding angiopoietin-2(ANGPT2),dual oxidase 2(DUOX2),coagulation factor Ⅲ(F3),interleukin-15(IL-15),lipocalin-2,and retinoic acid receptor-related orphan receptor B(RORB).Real-time quantitative PCR and Western blotting showed that the NPC cells had up-regulated mRNA and protein levels of ANGPT2 and IL-15 and down-regulated mRNA and protein levels of DUOX2,F3,and RORB,which was consistent with the results predicted by bioinformatics.Conclusion ANGPT2,DUOX2,F3,IL-15 and RORB are potential predictive molecular markers and therapeutic targets for NPC,which may be involved in Rap1,Ras,tumor necrosis factor and other signaling pathways.


Assuntos
Humanos , Carcinoma Nasofaríngeo/genética , Interleucina-15 , Oxidases Duais , Biologia Computacional , Neoplasias Nasofaríngeas/genética
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