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1.
J Ethnopharmacol ; 282: 114583, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34487850

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Herb-derived anti-tumor agents, such as paclitaxel and vincristine, exert significant but varied effectivenesses towards different cancer types. Similarly, Centipeda minima (CM) is a well-known traditional Chinese medicine that has been used to treat rhinitis, relieve pain and reduce swelling, and recently found to exert overwhelming anti-tumor effects against breast cancer, colon cancer, and nasopharyngeal carcinoma with different response rates. However, what is the optimizing cancer model that benefits most from CM, and what is the specific target underlying still require more exclusive and profound investigations. AIMS OF THE STUDY: This study aimed to explore the dominant tumor model and specific target of CM by integrative pharmacology and biological experiments. MATERIALS AND METHODS: The most predominant and specific cancer types that are sensitive to CM were screened and identified based on a combination network pharmacology and bioinformatics analysis. Compound-target network and protein-protein interaction of CM-related cancer targets were carried out to determine the most abundant active compound. Simultaneously, the priority target responsible for CM-related anti-tumor efficacy was further validated by molecular docking and in vitro experiments. RESULTS: In total, approximately 42% (8/19) of the targets were enriched in prostate cancer (p = 1.25E-09), suggesting prostate cancer would be the most sensitive tumor response to CM-related efficacy. Furthermore, we found that arnicolide D (ARD), the most abundant and representative active compound of CM, could directly bind to Src with binding energy of -7.3 kcal/mol, implying Src would be the priority target responsible for CM-related anti-tumor efficacy. Meanwhile, the results were further validated by solvent-induced protein precipitation (SIP) assay. In addition, PCR and WB results also revealed that either CM or ARD could not influence the gene expression of Src, while significantly decreased its protein expression instead, which further suggested that ARD might markedly shortene the Src protein half-life to promote Src protein degradation, thereby achieving significant anti-prostate cancer efficacy. CONCLUSION: Our findings not only suggest CM as a promising Src-targeting candidate for prostate cancer treatment, but also bring up a strategy for understanding the personalization of herbal medicines by using integrative pharmacology.

2.
Spectrochim Acta A Mol Biomol Spectrosc ; 266: 120468, 2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-34649124

RESUMO

The photometric method is widely used in real clinical tests due to its simple operation, low cost and convenient. Many of the reported colorimetric ALP assays so far are non- ratiometric because the detection was based on changes in absorbance at a single wavelength. The development of novel colorimetric and ratiometric assay is of importance for quantitatively measuring target with high accuracy. The challenge in the design of ratiometric photometric assay is that the chromophore must have a significant spectral shift before and after binding to the target. Here, we report a colorimetric and ratiometric photometric sequential assay of AA and ALP based on the complexation between ARS and Cu2+ and redox reaction between AA and Cu2+. The absorption band of ARS centered at 425 nm (yellow color), which could be shifted to 510 nm (red color) upon Cu2+ binding. However, as far as we know, this classic color reaction has not been used to develop a ratiometric photometric method to sequentially detect AA and ALP, although photometric methods based on the regulation of other color reagents with oxidizing metal ions have been reported. The proposed sensing system shows a limit of detection for ALP at 0.24 U L-1 and could be applied for detecting ALP in newborn calf serum. The established sensing system makes a useful contribution to the detection of ALP in complex clinical samples.


Assuntos
Fosfatase Alcalina , Colorimetria , Fosfatase Alcalina/metabolismo , Ácido Ascórbico , Humanos , Recém-Nascido , Limite de Detecção , Oxirredução , Espectrometria de Fluorescência
3.
Chin J Integr Med ; 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34731434

RESUMO

OBJECTIVE: To explore if acupoint injection can improve analgesic effects or delivery outcomes in parturients who received combined spinal-epidural analgesia (CSEA) and patient-controlled epidural analgesia (PCEA) for labor analgesia. METHODS: A total of 307 participants were prospectively collected from July 2017 to December 2019. The participants were randomized into the combined acupoint injection with CSEA plus PCEA group (AICP group, n=168) and CSEA plus PCEA group (CP group, n=139) for labor analgesia using a random number table. Both groups received CSEA plus PCEA at cervical dilation 3 cm during labor process, and parturients of the AICP group were implemented acupoint injection for which bilateral acupoint of Zusanli (ST 36) and Sanyinjiao (SP 6) were selected in addition. The primary outcome was Visual Analogue Scale (VAS) score, and the secondary outcomes were obstetric outcomes and requirement of anesthetics doses. Safety evaluations were performed after intervention. RESULTS: The VAS scores were significantly lower in the AICP group than in the CP group at 10, 30, 60, and 120 min after labor analgesia (all P<0.05). The latent phase of the AICP group was shorter than that of the CP group (P<0.05). There were less additional anesthetics consumption, lower incidences of uterine atony, fever, pruritus and urinary retention in the AICP group than those in the CP group (all P<0.05). CONCLUSION: Acupoint injection combined CSEA plus PCEA for labor analgesia can decrease the anesthetic consumption, improve analgesic quality, and reduce adverse reactions in the parturients. (Registration No. ChiMCTR-2000003120).

4.
Clin Transl Sci ; 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34729920

RESUMO

Previous exposure-response analyses for rituximab suggest that higher rituximab concentrations were associated with an improvement in efficacy, however, clinical studies investigating a higher rituximab dose had mixed results. To further explore the exposure-response relationship of rituximab, a prospective observational analysis was performed involving 121 newly diagnosed diffuse large B-cell lymphoma patients treated with triweekly R-CHOP. The trough concentration in the first cycle (C1-trough ) was significantly higher in patients achieving complete remission (CR) compared to patients that did not achieve complete remission (22.00 µg/mL vs. 16.62 µg/mL, P=0.0016), however, this difference between the two groups disappeared in later cycles. The relationship between rituximab C1-trough and achieving a CR was confirmed by matched-pair logistic regression analysis (OR, 0.79; P = 0.0020). In addition, a higher C1-trough (≥18.40 µg/mL) was associated with longer progression-free survival (P<0.0001) and overall survival (P=0.0038). The percentages of patients that did not achieve a CR and had recurrence after CR within 24 months were 35% and 22.50%, respectively, for patients with a C1-trough ≤18.40 µg/mL, compared with 12.35% and 6.17% for patients with C1-trough >18.40 µg/mL. Disease stage was found to be the most significant influencing factor of C1-trough , with 51.02% of patients at stage IV with an observed C1-trough <18.40 µg/mL. For these advanced patients, population pharmacokinetic (PK) simulations using an established model suggest that a loading dose of 800 mg/m2 may help to improve clinical outcomes.

5.
Amino Acids ; 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34837554

RESUMO

Taurine (Tau) is one of the most abundant amino acids in the brain and regulates physiological functions in the central nervous system, including anti-inflammatory effects. There is growing evidence that microglia-mediated neuro-inflammatory responses are an integral part of Parkinson's disease (PD) onset and progression. Among the many factors regulating the inflammatory response, phosphatidylinositol-3 kinase (PI3K) is susceptible to activation by a variety of cytokines and physicochemical factors, and subsequently recruits signaling proteins containing the pleckstrin homology structural domain to further regulate protein kinase B (AKT) expression involved in the regulation of the intracellular immune response and inflammatory response. Therefore, we established a PD mouse model using paraquat (PQ) intraperitoneal injection staining to explore the mechanism of Tau action on PI3K/AKT signaling pathway. Our study showed that PD mice with Tau intervention recovered motor and non-motor functions to some extent, and the number of dopaminergic (DAc) neurons in the substantia nigra and the level of dopamine (DA) secretion in the striatum were also significantly increased compared with the PQ-dyed group, and the protein content of PI3K and PDK-1 and the phosphorylation level of AKT were reduced in parallel with the reduction in the expression of microglia and related inflammatory factors. In conclusion, our results suggest that Tau may regulate microglia-mediated inflammatory responses through inhibition of the PI3K/AKT pathway in the midbrain of PD mice, thereby reducing DAc neurons damage.

6.
Chemosphere ; : 132890, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34801567

RESUMO

In order to clarify the role of oxygen vacancy (OV), five α-MnO2 catalysts with abundant OVs are fabricated via a novel and facile redox-precipitation approach and employed to the toluene oxidation in air. The concentration of OVs in α-MnO2 catalysts is regulated via the alkyl chain length of alcohols, and its correlation with catalytic performances is scientifically investigated based on various characterization technologies and density functional theory (DFT) calculation. The α-MnO2-C2 catalyst exhibits excellent catalytic activity (T90 = 217 °C), stability, and water resistance for toluene oxidation in air. The OVs can induce the new bandgap states (BGS), which upshift the antibonding orbitals relative to the Fermi level (Ef), eventually favoring the formation of adsorbed active oxygen species. Furthermore, the OVs cause an increase in the amount of Mn3+, resulting in the elongated Mn-O bonds due to the strong Jahn-Teller effect of Mn3+. Therefore, the synergistic effects of OVs benefit toluene oxidation through L-H and MvK mechanisms over the prepared α-MnO2-Cx catalysts. This work reveals the important role of OVs in the promotion of toluene catalytic oxidation activity and also may provide new insights for the design of high-performance VOCs oxidation elimination catalyst.

7.
Food Chem ; : 131612, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34823943

RESUMO

Novel zein and resveratrol conjugates were fabricated by alkaline and free radical grafting reactions. The grafting efficiency and total phenolic content of alkaline treated conjugates were slightly higher than those of free radical grafting. Compared to native and alkaline treated zein, the sulfhydryl contents of conjugates were obviously decreased, confirming that nucleophilic addition of resveratrol to sulfhydryl group of zein formed stable CS covalent bonds. The conformation changes of zein modified by resveratrol were revealed by fourier transform infrared spectroscopy and fluorescence spectroscopy. Moreover, covalent modification changed isoelectric point of zein from 6.5 to 5.4 (alkaline) or 5.6 (free radical grafting), and broadening the pH application range of zein. It was worth mentioning that the conjugates showed much higher thermal stability, antioxidant activity, and emulsify activity than those of native zein. This study provides an effective way for the design of novel delivery systems to encapsulate bioactive substances.

8.
Cell Death Discov ; 7(1): 353, 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34775471

RESUMO

Patients with EGFR mutations in non-small cell lung cancer (NSCLC) have been greatly benefited from gefitinib, however, the therapeutic has failed due to the presence of acquired resistance. In this study, we show that gefitinib significantly induces downregulation of Sterol Regulator Element Binding (SREBP1) in therapy-sensitive cells. However, this was not observed in EGFR mutant NSCLC cells with acquired resistance. Lipidomics analysis showed that gefitinib could differently change the proportion of saturated phospholipids and unsaturated phospholipids in gefitinib-sensitive and acquired-resistant cells. Besides, levels of ROS and MDA were increased upon SREBP1 inhibition and even more upon gefitinib treatment. Importantly, inhibition of SREBP1 sensitizes EGFR-mutant therapy-resistant NSCLC to gefitinib both in vitro and in vivo models. These data suggest that sustained de novo lipogenesis through the maintenance of active SRBEP-1 is a key feature of acquired resistance to gefitinib in EGFR mutant lung cancer. Taken together, targeting SREBP1-induced lipogenesis is a promising approach to overcome acquired resistance to gefitinib in EGFR-mutant lung cancer.

9.
Inflammation ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34792688

RESUMO

Intestinal inflammation is a common disease which can further lead to inflammatory bowel disease and even intestinal cancer. The increasing focus has come to the role of short-chain fatty acid (SCFA) in various bowel diseases. Hence, this study was designed to explore the specific role of SCFA in intestinal inflammation. In vivo and in vitro models of intestinal inflammation were constructed by lipopolysaccharide (LPS) injection in mice and LPS treatment on intestinal epithelial cells. A possible regulatory mechanism involving SCFA, CCAAT enhancer-binding protein beta (CEBPB), microRNA-145 (miR-145), and dual-specificity phosphatase 6 (DUSP6) in intestinal inflammation was verified by ChIP assay and dual-luciferase reporter gene assay. To evaluate the effects of SCFA on LPS-treated intestinal epithelial cells, the expression of relevant genes and inflammatory factors (IL-6, TNF-α, and IL-1ß) were determined. Last, the role of SCFA in vivo was explored through the scoring of disease activity index (DAI) and observation of colonic histology of LPS-treated mice. SCFA decreased the CEBPB expression in mouse colon tissues and small intestine epithelial cells induced by LPS. Furthermore, CEBPB could bind to the miR-145 promoter to inhibit its expression, thereby promoting the expression of DUSP6. In addition, SCFA improved the DAI, colonic histology, and the expression of serum inflammatory factors in LPS-treated mice and cells, noting that SCFA alleviated intestinal inflammation in vitro and in vivo. To sum up, SCFA inhibited DUSP6 by upregulating miR-145 through CEBPB repression and thus prevented the development of intestinal inflammation.

10.
mBio ; : e0297521, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34781736

RESUMO

Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have arisen that exhibit increased viral transmissibility and partial evasion of immunity induced by natural infection and vaccination. To address the specific antibody targets that were affected by recent viral variants, we generated 43 monoclonal antibodies (mAbs) from 10 convalescent donors that bound three distinct domains of the SARS-CoV-2 spike. Viral variants harboring mutations at K417, E484, and N501 could escape most of the highly potent antibodies against the receptor binding domain (RBD). Despite this, we identified 12 neutralizing mAbs against three distinct regions of the spike protein that neutralize SARS-CoV-2 and variants of concern (VOCs), including B.1.1.7 (alpha), P.1 (gamma), and B.1.617.2 (delta). Notably, antibodies targeting distinct epitopes could neutralize discrete variants, suggesting that different variants may have evolved to disrupt the binding of particular neutralizing antibody classes. These results underscore that humans exposed to the first pandemic wave of prototype SARS-CoV-2 possess neutralizing antibodies against current variants and that it is critical to induce antibodies targeting multiple distinct epitopes of the spike that can neutralize emerging variants of concern. IMPORTANCE We describe the binding and neutralization properties of a new set of human monoclonal antibodies derived from memory B cells of 10 coronavirus disease 2019 (COVID-19) convalescent donors in the first pandemic wave of prototype SARS-CoV-2. There were 12 antibodies targeting distinct epitopes on spike, including two sites on the RBD and one on the N-terminal domain (NTD), that displayed cross-neutralization of VOCs, for which distinct antibody targets could neutralize discrete variants. This work underlines that natural infection by SARS-CoV-2 induces effective cross-neutralization against only some VOCs and supports the need for COVID-19 vaccination for robust induction of neutralizing antibodies targeting multiple epitopes of the spike protein to combat the current SARS-CoV-2 VOCs and any others that might emerge in the future.

11.
Opt Express ; 29(24): 39186-39199, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34809288

RESUMO

Dynamically switchable light transmission/absorption functionality is highly desirable in sensing and functional devices. However, the operating bandwidth of the newly emerging schemes using resonant meta-structures is inherently limited. In this work, we design and numerically demonstrate a non-resonant tilted anisotropic metamaterial consisting of phase-change materials. When the phase transition of the phase-change material from amorphous phase to crystalline phase occurs, the functionality of the metamaterial can be switched from perfect transparency to perfect absorption for transverse-magnetic polarization under oblique incidence over a broad spectrum. Such a remarkable phenomenon originates in the anomalous Brewster effect, which enables broadband reflectionless transmission/absorption of light under the anomalous Brewster's angle. Moreover, gradient metamaterials exhibiting dynamically controllable functionality for incident light with an almost arbitrary wavefront are demonstrated. The proposed metamaterials are simple but highly efficient, which may find applications in sensing and advanced and intelligent optical devices.

12.
Zootaxa ; 5061(3): 510-522, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34810611

RESUMO

Five new species, Eurhadina (Singhardina) dissimilis, E. (S.) flatilis, E. (S.) fumosa, E. (S.) furca and E. (S.) immatura spp. nov., and two new records, E. (S.) krispinilla rec. nov., E. (S.) pookiewica rec. nov. of the leafhopper subgenus Eurhadina (Singhardina) Mahmood from China are described and illustrated and a key to all members of the E. (S.) robusta species group is provided.


Assuntos
Proteínas de Drosophila , Hemípteros , Animais , China , Drosophila
14.
Int J Biol Macromol ; 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34767882

RESUMO

Osteoporosis is a systemic metabolic bone disease with an increasing incidence rate. Chinese medicinal herbs have a long history of treating bone diseases. Polysaccharides are an important category of phytochemicals in Chinese medicinal herbs, and their health benefits have increased the interest of the public. Numerous studies have indicated that polysaccharides exhibit anti-osteoporosis effects by balancing bone resorption and bone formation, but the detailed effects and mechanism have not been systematically summarized. We performed a comprehensive review of the literature to consolidate studies for the period 2000-2021 by conducting electronic searches on the PubMed, CNKI, VIP, and Wanfang databases. In total, polysaccharides from 19 kinds of Chinese medicinal herbs in 54 studies have shown bone homeostasis protective properties. In vivo and in vitro experiments have demonstrated that polysaccharides present properties in the treatment of postmenopausal osteoporosis, senile osteoporosis, and glucocorticoid-induced secondary osteoporosis, especially postmenopausal osteoporosis. Moreover, a number of signalling pathways, such as the Wnt/ß-catenin signalling pathway, BMP/SMAD/RUNX2 signalling pathway, OPG/RANKL/RANK signalling pathway, apoptosis pathway, and transcription factors, are regulated by polysaccharides and participate in improving bone homeostasis. This review will provide a better understanding of the anti-osteoporotic effects of polysaccharides and the concomitant modulations of signalling pathways.

15.
Front Immunol ; 12: 697622, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777333

RESUMO

Objectives: The longitudinal and systematic evaluation of immunity in coronavirus disease 2019 (COVID-19) patients is rarely reported. Methods: Parameters involved in innate, adaptive, and humoral immunity were continuously monitored in COVID-19 patients from onset of illness until 45 days after symptom onset. Results: This study enrolled 27 mild, 47 severe, and 46 deceased COVID-19 patients. Generally, deceased patients demonstrated a gradual increase of neutrophils and IL-6 but a decrease of lymphocytes and platelets after the onset of illness. Specifically, sustained low numbers of CD8+ T cells, NK cells, and dendritic cells were noted in deceased patients, while these cells gradually restored in mild and severe patients. Furthermore, deceased patients displayed a rapid increase of HLA-DR expression on CD4+ T cells in the early phase, but with a low level of overall CD45RO and HLA-DR expressions on CD4+ and CD8+ T cells, respectively. Notably, in the early phase, deceased patients showed a lower level of plasma cells and antigen-specific IgG, but higher expansion of CD16+CD14+ proinflammatory monocytes and HLA-DR-CD14+ monocytic-myeloid-derived suppressor cells (M-MDSCs) than mild or severe patients. Among these immunological parameters, M-MDSCs showed the best performance in predicting COVID-19 mortality, when using a cutoff value of ≥10%. Cluster analysis found a typical immunological pattern in deceased patients on day 9 after onset, which was characterized as the increase of inflammatory markers (M-MDSCs, neutrophils, CD16+CD14+ monocytes, and IL-6) but a decrease of host immunity markers. Conclusions: This study systemically characterizes the kinetics of immunity of COVID-19, highlighting the importance of immunity in patient prognosis.


Assuntos
COVID-19/imunologia , SARS-CoV-2 , Imunidade Adaptativa , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Linfócitos B/imunologia , COVID-19/sangue , COVID-19/classificação , COVID-19/fisiopatologia , Citocinas/sangue , Células Dendríticas/imunologia , Feminino , Humanos , Imunidade Inata , Imunoglobulina G/sangue , Células Matadoras Naturais/imunologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , Índice de Gravidade de Doença , Linfócitos T/imunologia
16.
Front Immunol ; 12: 753290, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804038

RESUMO

Background: This study aimed to assess the host immune signatures associated with EBV infection and its clinical value in indicating the severity of children with acute infectious mononucleosis (IM). Methods: Twenty-eight pediatric patients with IM aged 3-8 years were enrolled. The immune phenotypes and cytokine secretion capability of T cells were detected. Results: The percentages and absolute numbers of CD3+ and CD8+ T cells were significantly increased in IM patients compared with HCs. The percentages of Naïve CD4+ and CD8+ T cells were decreased but with increased percentages of memory CD4+ and CD8+ T subsets. Our results showed the upregulation of active marker HLA-DR, TCR-αß, and inhibitory receptors PD-1, TIGIT in CD8+ T cells from IM patients, which suggested that effective cytotoxic T cells were highly against EBV infection. However, EBV exposure impaired the cytokine (IFN-γ, IL-2, and TNF-α) secretion capability of CD4+ and CD8+ T cells after stimulation with PMA/ionomycin in vitro. Multivariate analysis revealed that the percentage of HLA-DR+ CD8+ T cells was an independent prognostic marker for IM. The percentage of HLA-DR+ CD8+ T cells was significantly correlated with high viral load and abnormal liver function results. Conclusion: Robust expansion and upregulation of HLA-DR in CD8+ T cells, accompanied with impaired cytokine secretion, were typical characteristics of children with acute IM. The percentage of HLA-DR+ CD8+ T cells might be used as a prominent marker not only for the early diagnosis but also for indicating the severity of IM.

17.
Opt Express ; 29(24): 40447-40461, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34809385

RESUMO

With the development of wide color gamut displays, several recent studies investigated the performance of the CIE standard color matching functions (CMFs) in characterizing the color matches and observer metamerism between different primary sets. These studies, however, always employed different primaries to produce color stimuli, which failed to isolate the effect of the peak wavelength from that of the spectral shape. In this study, we carefully selected primaries with similar spectral shapes but different peak wavelengths. Human observers adjusted the intensities of the seven matching primary sets to match the color appearance of six stimuli, with a field of view around 5.7° × 5.7°, produced using a reference primary set, which was the same as one of the matching primary sets. The results clearly revealed the significant effect of the primary peak wavelength, and the failure of using chromaticities to characterize color matches using different primaries. The CIE 2006 2° CMFs were found to have the best performance in characterizing the color matches on average among the four CIE standard CMFs (i.e., the CIE 1931 2°, CIE 1964 2°, CIE 2006 2°, and CIE 2006 10° CMFs), which did not support the CIE's recommendation of using the 10° CMFs for stimuli beyond 4°. When the two categorical observer CMFs (i.e., Sarkar 2 set and Beijing Institute of Graphic Communication "BIGC" 17 set) were considered together, the BIGC 17 set had the best performance on average. More importantly, the performance of the CMFs varied with the primary sets. When the matching and reference sets were the same, the performance of all the CMFs were consistently good. In contrast, when the blue or green primary, or both of the two primaries, was shifted, the performance of all the CMFs became much worse. This clearly implies the importance of considering primary wavelengths when specifying color matches using different CMFs.

18.
Ann Transl Med ; 9(18): 1434, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34733986

RESUMO

Background: To analyze the imaging features of coronary artery-to-pulmonary artery fistula (CPAF) on coronary computed tomography angiography (CCTA). Methods: This was a retrospective study of 3,975 patients who underwent 320 row detector CCTA examinations in our hospital from May 2015 to July 2020. A total of 22 patients who diagnosed with CPAF were reviewed for CCTA imaging characteristics, including the origin, number, blood volume, opening size, and course of fistula vessels, and the drainage site, size, and imaging features of the fistula. All cases were analyzed for the presence of coronary atherosclerotic plaque and that of deficient left ventricular myocardial perfusion. Results: A total of 22 CPAF cases detected by CCTA were collected (men, 11; women, 11; median age, 59.6±10.1 years). There were 7, 10, and 5 cases detected with 1, 2, and 3 fistula vessels, respectively, among which 4 originated from the left coronary artery, 4 from the right coronary artery, and 14 had bilateral origins. There were 10 cases in which the fistula vessels presented as a worm-like tortuous dilation with (n=5) or without (n=5) aneurysm, while 12 cases showed malformed vascular networks with (n=8) or without (n=4) aneurysm, respectively. The calculated incidence of aneurysm formation was 59.09%, and fistula vessels with an aneurysm had larger blood volume than those without. All fistula showed a single drainage site, with an average diameter of 2.81±1.48 mm where the diameter of fistula with aneurysm was larger than that without. The fistula vessels drained into the left anterolateral and anterior walls of main pulmonary artery and the proximal left inferior PA, respectively. Typical jet sign, smoke sign, and isodensity sign were presented in 22, 14 and 1 case, respectively. For the coexistent abnormalities analyzed in 22 cases, 17 participants with CPAF demonstrated hypoperfusion of the fistula vessels, and 11 demonstrated calcified plaque accompanied with luminal stenosis to different degrees. Conclusions: The 320-row detector CCTA can comprehensively characterize the morphological features of CPAF, which is an optimal choice for physicians to make an accurate assessment before formulating patient management strategies.

19.
Acta Pharmacol Sin ; 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34737420

RESUMO

Gefitinib has been available in the market for 20 years, but its pharmacokinetic mechanism of response is little known. In this study, we examined the pharmacokinetic and metabolomic profiles in non-small cell lung cancer (NSCLC) patients with sensitive EGFR mutations. A total of 216 advanced NSCLC patients were enrolled, and administered gefitinib at the standard dosage of 250 mg/day, which was established in heterogeneous subjects with non-sensitive mutations. We identified and quantified three main metabolites (named as M1, M2 and M3) in the plasma of patients, the correlations between the concentration of gefitinib/metabolites and efficacy were analyzed. In exploratory and validation set, gefitinib concentration was not correlated with clinical effects. Considering the result that the therapeutic effects of 250 mg/2-day was better than that of 250 mg/day in a multiple center clinical trial, the standard dose might be higher than that for maximal efficacy according to the hypothetical dose-response curve. Among the three metabolites, the IC50 of M2 in HCC827 and PC9 cell lines was significantly lower, and Conc.brain/Conc.plasma of M2 in mice was significantly higher than those of gefitinib, suggesting its higher potential to penetrate blood-brain barrier and might be more effective in the treatment of brain metastatic tumor than gefitinib. Consistently and attractively, higher M2 plasma concentration was found to be correlated with better clinical outcome in patients with brain metastases (the median PFS of CM2 < 12 ng/mL and CM2 ≥ 12 ng/mL were 17.0 and 27.1 months, respectively, P = 0.038). The plasma concentration of M2 ≥ 12 ng/mL was a strong predictor of the PFS of NSCLC patients. In conclusion, for NSCLC patients with EGFR sensitive mutations, the standard dose is suspectable and could be decreased reasonably. M2 plays an important role in efficacy and may be more effective in the treatment of metastatic tumor than gefitinib.

20.
Taiwan J Obstet Gynecol ; 60(6): 1078-1083, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34794741

RESUMO

OBJECTIVE: High-intensity focused ultrasound (HIFU) therapy is a noninvasive alternative to conventional abdominal surgery in obstetrics and gynecology. The aim of this study is to evaluate the reduction of pain intensity with bowel manipulation before ultrasound-guided HIFU treatment in women with posterior wall uterine fibroids and/or adenomyosis. MATERIALS AND METHODS: This is a multicenter retrospective observational study. Data from all patients who underwent HIFU therapy at three HIFU clinics (Sichuan Maternal and Child Health Hospital, Xiangya Hospital of Central South University, and Kuo General Hospital) between January 2019 and December 2019 were analyzed. We compared pain intensity with and without bowel manipulation during the HIFU treatment and evaluated tolerability without intravenous sedation. The presence of discomfort or pain during the HIFU procedure was evaluated using the visual analog scale (VAS). RESULTS: A total of 86 women were included in this study. All women underwent HIFU therapy with the PRO-2008 system in the supine position for posterior wall uterine fibroids and/or adenomyosis. Thirty-seven women received pretreatment anal catheterization with a condom and 49 women were not subjected to bowel manipulation. All patients received pretreatment condom-catheter device were well tolerated during the procedure of bowel manipulation. During the HIFU procedure, the women who had received bowel manipulation experienced lower pain intensity, especially less sacrococcygeal pain (VAS score 1.56 ± 1.46 vs 2.89 ± 1.61), target region pain (1.54 ± 1.30 vs 2.53 ± 1.29), and radiating pain (0.13 ± 0.34 vs 0.41 ± 0.54), compared with the women without bowel manipulation. CONCLUSION: Bowel manipulation with anal catheterization before HIFU therapy for posterior wall uterine masses can be safely performed and is effective as a low risk intervention to aid in reducing potential HIFU complications related to nerve involvement.

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