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1.
BMC Endocr Disord ; 21(1): 184, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34517857

RESUMO

BACKGROUND: There is no clear conclusion on the relationship between thyroid disease and obesity and lifestyle factors such as smoking and drinking. In this study, we analysed the association of body mass index (BMI), smoking and drinking with subclinical hypothyroidism (SHO) and thyroid nodules (TNs) with the results of a cross-sectional survey of urban residents in central China and discussed the potential mechanism linking these predictive factors and the two diseases. METHODS: This study included 1279 participants who were recruited from a Chinese community in 2011 and 2012. A questionnaire, laboratory examination and ultrasound diagnosis were conducted on these participants. Binary logistic regression analysis was used to analyse these factors. RESULTS: Overweight (BMI ≥ 25 kg/m2) was closely related to SHO and TNs in univariate and multivariate logistic regression analyses. Smoking had a protective effect on SHO and TNs, while drinking had a protective effect on TNs in univariate logistic regression and multivariate logistic regression with some covariates, but there was no significant difference between smoking and drinking and the two kinds of thyroid diseases in multivariate logistic regression analysis with all the covariates. In subgroup analysis, BMI ≥ 25 kg/m2 was significantly associated with SHO in people with positive thyroid antibodies (odds ratio (OR) = 2.221, 95 % confidence interval (CI): 1.168-4.184, P = 0.015) and smokers (OR = 2.179, 95 % CI: 1.041-4.561, P = 0.039). BMI ≥ 25 kg/m2 was significantly associated with TNs in people over 60 years old (OR = 2.069, 95 % CI: 1.149-3.724, P = 0.015) and drinkers (OR = 3.065, 95 % CI: 1.413-6.648, P = 0.005). Drinking alcohol had a protective effect on TNs in smokers (OR = 0.456, 95 % CI: 0.240-0.865, P = 0.016) and people with BMI ≥ 25 kg/m2 (OR = 0.467, 95 % CI: 0.236-0.925, P = 0.029). No significant association was found between smoking and the two thyroid diseases in different subgroups. CONCLUSIONS: Obesity is a risk factor for both TNs and SHO, especially in elderly individuals and people with positive thyroid autoantibodies. Obesity and metabolic syndrome may be more associated with TNs than SHO. Smoking may have a protective effect on thyroid disease, while drinking may have a protective effect only on TNs.

3.
Artif Intell Med ; 119: 102130, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34531004

RESUMO

As a widely used vital sign within cardiology, Electrocardiography (ECG) provides the basis for assessing heart function and diagnosing cardiovascular diseases. Automated anomaly detection for ECG plays an important role in improving patient diagnosis efficiency and reducing healthcare costs. Practically, due to the limits of electronics support or the medical system setting, image is a more common format for large-scale ECG storage in most clinical institutions. To guarantee an automated ECG detection model's scalability and practicality in clinical applications, taking good advantage of ECG images is crucial. However, existing time digital-based discriminative models fail to learn from images effectively for two reasons. First of all, the signals recorded on images have much lower resolution and higher noise, which makes it impractical to extract precise ECG signals following existing techniques. Meanwhile, the differences between abnormal signals are usually subtle, and they may be overwhelmed by the noises in the images as well. Towards this end, we design a novel neural framework that can be directly applied to massive ECG images determining various types of cardiology abnormalities. It classifies fine-grained ECG images based on weakly supervised strategy, in which case only image-level labeling is required. By eliminating the need for part annotations, the proposed method can result in significant savings in annotation time and cost. The effectiveness of the method is demonstrated by experimental results on two real ECG datasets.

4.
Stem Cell Res Ther ; 12(1): 507, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34535194

RESUMO

BACKGROUND: Our previous study proved that Salvia miltiorrhiza could enhance fat graft survival by promoting adipogenesis. However, the effect of salvianolic acid B (Sal-B), the most abundant and bioactive water-soluble compound in Salvia miltiorrhiza, on fat graft survival has not yet been investigated. OBJECTIVE: This study aims to investigate whether salvianolic acid B could improve fat graft survival and promote preadipocyte differentiation. The underlying mechanism has also been studied. METHODS: In vivo, 0.2 ml of Coleman fat was transplanted into nude mice with salvianolic acid B. The grafts were evaluated by HE and IF at 2 and 4 weeks posttransplantation and by micro-CT at 4 weeks posttransplantation. In vitro, the adipogenesis and proliferative activities of salvianolic acid B were analyzed in cultured human adipose-derived stem cells (h-ADSCs) and 3T3-L1 cells to detect the mechanism by which salvianolic acid B affects graft survival. RESULTS: In vivo, the weights and volumes of the fat grafts in the Sal-B-treated groups were significantly higher than those of the fat grafts in the control group. In addition, higher fat integrity and more viable adipocytes were observed in the Sal-B-treated groups. In vitro, salvianolic acid B showed the ability to promote 3T3-L1 and h-ADSC proliferation and adipogenesis. CONCLUSIONS: Our in vitro experiments demonstrated that salvianolic acid B can promote the proliferation of adipose stem cells and enhance the differentiation of adipose stem cells. Simultaneously, in vivo experiments showed that salvianolic acid B can improve the survival rate of fat transplantation. Therefore, our research shed light on the potential therapeutic usage of salvianolic acid B in improving the survival rate of fat transplantation.

5.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(9): 951-958, 2021.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34535212

RESUMO

OBJECTIVES: To study the effect of puromycin aminonucleoside (PAN) on the apoptosis of mouse podocyte clone 5 (MPC-5) and the expression of recombinant human Parkinson's disease 7 (Park7) and to study the protective mechanism of tacrolimus (FK506) against MPC-5 injury. METHODS: MPC-5 cells were cultured in vitro and then divided into three groups: blank control (control), PAN, and FK506. The cells in the PAN group were added with PAN (with a concentration of 50 mg/L) to establish a model of MPC-5 injury, and those in the FK506 group were added with PAN (with a concentration of 50 mg/L) and FK506 (with a concentration of 5 mg/L). An inverted microscope was used to observe the morphology and structure of MPC-5 cells at 12, 24, and 48 hours after treatment. Flow cytometry was used to measure cell apoptosis rate. Quantitative real-time PCR was used to measure the mRNA expression of Park7. Western blot and immunofluorescent staining were used to measure the protein expression of Park7. RESULTS: The control group had a large number of foot processes of the cell body at all time points, with tight connections between cells and a normal morphology. Compared with the control group, the PAN group had a significantly smaller cell volume at all time points, with loose connections between cells and the presence of ruptured cells. Compared with the PAN group, the FK506 group had an increased cell volume at all time points, with tighter connections between cells and a better morphology. The PAN group had a significantly higher apoptosis rate than the control group at all time points. Compared with the PAN group, the FK506 group had a significant reduction in the apoptosis rate at all time points (P<0.01). The PAN group had a significantly higher mRNA expression level of Park7 than the control group at all time points. Compared with the PAN group, the FK506 group had a significant reduction in the mRNA expression level of Park7 at all time points (P<0.01). Western blot showed that the PAN group had a significantly higher protein expression level of Park7 than the control group at all time points. Compared with the PAN group, the FK506 group had a significant reduction in the protein expression level of Park7 at all time points (P<0.01). Immunofluorescent staining showed that in the PAN group, there was a significantly lower expression of Park7 protein in cell membrane and cytoplasm, with a dense cluster distribution and increased fluorescence intensity. Compared with the PAN group, the FK506 group had a significant improvement in the distribution of Park7 protein. CONCLUSIONS: PAN can act on MPC-5 cells and cause morphological and structural damage and apoptosis of MPC-5 cells, as well as upregulated mRNA and protein expression of Park7. FK506 can downregulate the mRNA and protein expression of Park7 in the model of MPC-5 injury, maintain cellular homeostasis, reduce proteinuria, and delay glomerulosclerosis.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34525249

RESUMO

Atomically dispersed metal-nitrogen sites show great prospect for the oxygen reduction reaction (ORR), whereas the unsatisfactory adsorption-desorption behaviors of oxygenated intermediates on the metal centers impede improvement of the ORR performance. We propose a new conceptual strategy of introducing sacrificial bonds to remold the local coordination of Fe-N x sites, via controlling the dynamic transformation of the Fe-S bonds in the Fe-N-C single-atom catalyst. Spectroscopic and theoretical results reveal that the selective cleavage of the sacrificial Fe-S bonds induces the incorporation of the electron-withdrawing oxidized sulfur on the Fe centers. The newly functionalized moieties endow the catalyst with superior ORR activity and remarkable stability, owing to the reduced electron localization around the Fe centers facilitating the desorption of ORR intermediates. These findings provide a unique perspective for precisely controlling the coordination structure of single-atom materials to optimize their activity.

7.
Bioengineered ; 12(1): 5516-5528, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34528498

RESUMO

A disintegrin and a metalloprotease (ADAM)9 upregulated within human hepatocellular carcinoma (HCC) cells, but its effect on HCC radiosensitivity remains unknown. The present work aimed to examine the effect of ADAM9 on HCC radiosensitivity and to reveal its possible mechanism, which may be helpful in identifying a potential therapeutic strategy. Changes in ADAM9 expression after X-ray irradiation were identified using western blot, qRT-PCR, and immunofluorescence. ADAM9 stable knockdown and overexpression cell lines were constructed using lentivirus packaging. The radiosensitivity of HCC cells with altered ADAM9 expression was examined by CCK-8 assays, subcutaneous tumorigenesis experiments, and clone formation assays. This study also determined how autophagy affected HCC cell radiosensitivity. Furthermore, ADAM9, p62 and Bax expressions in HCC tissues that were removed after radiotherapy were detected by immunohistochemistry, and the relationship among the levels of these molecules was statistically analyzed. The level of ADAM9expression in HCC cells increased after X-ray irradiation. Through CCK-8 assays, subcutaneous tumorigenesis experiments, and clone formation assays, this work discovered the increased MHCC97H cell radiosensitivity after ADAM9 knockdown, and the radiosensitivity of Huh7 cells decreased after the overexpression of ADAM9. Furthermore, ADAM9 induced HCC cell autophagy via downregulating Nrf2 expression, while autophagy inhibition or induction reversed the effects of altered ADAM9 expression on radiosensitivity. Moreover, ADAM9 level showed a negative correlation with Bax and p62 expression within HCC tissues after radiotherapy. Taken together, ADAM9 decreased the radiosensitivity of HCC cells, and autophagy mediated this process.

8.
Nanoscale ; 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34528651

RESUMO

Plexcitonic hybrids, consisting of metal nanoparticles and J-aggregates, are effective nanostructures to achieve a strong coupling regime. The chirality of the exciton in the strong coupled plexcitons provides more potential for the design of advanced optoelectronic devices. Here, we experimentally measured the circular dichroism (CD) spectra of plexcitonic hybrids, and researched the diverse chirality of J-aggregates assembled on the surface of the achiral Au nanorods. We found that the chirality of J-aggregates is not only related to the quantity of dye molecules in the plexcitonic, but also to the distribution in different positions of the nanorods, by analyzing the composition of the CD spectra with a quasistatic theory. The J-aggregates assembled on both ends and both sides of the nanorods had opposite chirality. The interaction between the longitudinal localized surface plasmon resonance (LLSPR) of the nanorods and J-aggregates achieved the strong coupling regime, and Rabi splitting of about 198.3 meV was observed. The research into the chirality of the plexcitons provided more detail on the chiral J-aggregates assembly on the nanoparticles, and give a perspective on the development of the strong coupling interactions and the design of optoelectronic systems.

9.
Cancer Med ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34523816

RESUMO

BACKGROUND: Women with endometrial cancer (EC) have favorable prognoses, leaving them vulnerable to the development of second primary cancers (SPCs). We investigated the SPC risk and survival outcomes among EC patients treated with surgery alone in order to exclude the impact of adjuvant treatment on the results. METHODS: Data from the Taiwan Cancer Registry from 1995 to 2013 were analyzed. Standardized incidence ratios (SIRs) of SPCs among EC survivors were calculated. RESULTS: Among 7725 women enrolled, 478 developed an SPC. The overall SIR for SPCs in EC survivors was 2.84 (95% confidence interval [CI] 2.59-3.10) compared with the general female population. Women diagnosed with EC at age <50 years had a higher SIR for an SPC than those diagnosed at age ≥50 years (SIR = 4.38 vs. 1.28). The most frequent site of an SPC was the small intestine (SIR = 8.39, 95% CI 2.72-19.58), followed by the kidney (SIR = 4.84, 95% CI 1.78-10.54), and oral cavity (SIR = 4.52, 95% CI 2.17-8.31). Women, regardless of age at EC diagnosis, had significantly higher SIRs for subsequent breast, colorectal, lung, and thyroid cancer, and lymphoma. Women with an SPC had shorter overall survival than those without (5-year: 88.9 vs. 94.2%, 10-year: 71.3 vs. 89.8%, 15-year: 62.3 vs. 86.1%, and 20-year: 47.6 vs. 81.1%, all ps<0.001). CONCLUSIONS: Even women treated for EC with surgery alone, especially young EC survivors, had an increased risk of SPCs. Genetic counseling/testing is recommended for young EC patients, and all are recommended to receive regular surveillance and screening for breast, colorectal, and lung cancers.

10.
Chemistry ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519381

RESUMO

Wastewater treatment is of great significance to environmental remediation. The exploration of efficient and stable methods for wastewater treatment is still a challenging issue. Herein, a heterojunction material with photocatalysis and adsorption properties has been designed to remove the complex pollutants from wastewater. The heterojunction material (ZnO/TiO2-PW12, PW12= [PW12O40]3-) was synthesized by calcining the ZnTi-layered double hydroxide (ZnTi-LDH) intercalated with the Keggin-type polyoxometalate H3PW12O40. In the construction of ZnO/TiO2-PW12, it was found that the polyanionic PW12 remained unchanged in the process of forming the proposed heterojunction. The photochemical properties verifies that heterojunction synergistic with PW12 facilitated the separation of photoproduced electron-hole pairs and thus suppressed the recombination. Therefore, ZnO/TiO2-PW12 exhibits excellent photocatalytic properties, and the efficiency of Cr(VI) photoreduction reached more than 90% in the first 3 min. Furthermore, the electrostatic force between the PW12 and cationic dyes makes ZnO/TiO2-PW12 have an outstanding adsorption performance for cationic dyes such as rhodamine B, crystal violet and methyl blue. Such the heterojunction material combined with polyoxometalate puts forwards new insights for the design of functional materials for water treatment with low cost and high efficiency.

11.
Acta Crystallogr F Struct Biol Commun ; 77(Pt 9): 319-327, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34473109

RESUMO

In situ microplates are small in size, crystal cultivation and operation are difficult, and the efficiency of crystal screening is relatively low. To solve this problem, a novel combined crystallization plate was designed for high-throughput crystal cultivation and in situ data collection. A frame was used to hold 48 in situ microplates, and the in situ microplates were sealed on one side with an ultralow background-scattering Kapton film. An automatic liquid handler (Mosquito) was used to add a liquid drop to the in situ microplates in the frame, and CrystalClear HD tape was used to seal the frame. A sealed frame holding 48 microplates was developed as a novel combined crystallization plate and was used for crystal cultivation under different conditions and in situ data collection at the synchrotron beamline. Moreover, individual microplates can be separated from the combined crystal plate and then fixed on a magnetic base or loaded onto a UniPuck for in situ data collection. Automatic grid scanning was used to locate crystals. The efficiency of the combined crystallization plate for crystal screening was verified. This method avoids the manual manipulation of crystals during crystal screening and diffraction data collection; therefore, the combined crystallization plate is suitable for large-scale screening of microcrystals.

12.
Nat Commun ; 12(1): 5245, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475396

RESUMO

State-of-the-art silicon probes for electrical recording from neurons have thousands of recording sites. However, due to volume limitations there are typically many fewer wires carrying signals off the probe, which restricts the number of channels that can be recorded simultaneously. To overcome this fundamental constraint, we propose a method called electrode pooling that uses a single wire to serve many recording sites through a set of controllable switches. Here we present the framework behind this method and an experimental strategy to support it. We then demonstrate its feasibility by implementing electrode pooling on the Neuropixels 1.0 electrode array and characterizing its effect on signal and noise. Finally we use simulations to explore the conditions under which electrode pooling saves wires without compromising the content of the recordings. We make recommendations on the design of future devices to take advantage of this strategy.


Assuntos
Eletrodos Implantados , Eletrofisiologia/métodos , Espaço Extracelular/fisiologia , Silício/química , Potenciais de Ação , Animais , Encéfalo/fisiologia , Eletrofisiologia/instrumentação , Desenho de Equipamento , Camundongos , Rede Nervosa/fisiologia , Neurônios/fisiologia , Processamento de Sinais Assistido por Computador
13.
Zhongguo Zhong Yao Za Zhi ; 46(15): 3832-3837, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34472256

RESUMO

Freshly collected seeds of Amomum tsaoko demonstrate obvious dormancy. Therefore, the selection of stable reference genes during seed dormancy release is very important for the subsequent functional research of related genes. In this study, ten commonly used reference genes(GAPDH, 40S, actin, tubulin, EIF4A-9, EIF2α, UBC, UBCE2, 60S, and UBQ) were selected as candidates for quantitative Real-time polymerase chain reaction(qRT-PCR) of the embryo samples of A. tsaoko at different dormancy release stages. Three kinds of software(BestKeeper, geNorm, and Normfinder) and the Delta CT method were used to evaluate the expression stability of the candidate reference genes, and the RefFinder online tool was employed to integrate the results and generate a comprehensive ranking. The results showed that the expression levels of the ten candidate reference genes differed greatly in different embryo samples. GAPDH and UBC had high expression levels, as manifested by the small Ct values. GeNorm identified 40S and UBCE2 as the most stable genes. NormFinder ranked EIF2α as the most stable gene and UBC as the least stable gene. UBCE2 was found to be the most stable gene and actin the least stable one by BestKeeper. Delta CT analysis suggested that the expression of 40S was most stable. UBCE2 was recommended as the most stably expressed gene by RefFinder. Thus, UBCE2 is the ideal reference gene for qRT-PCR analysis of A. tsaoko seeds at different dormancy release stages. The results may lay a foundation for analyzing the expression of related genes during seed dormancy release of A. tsaoko.


Assuntos
Amomum , Perfilação da Expressão Gênica , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sementes/genética
14.
J Hazard Mater ; 423(Pt A): 127040, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34474366

RESUMO

Osmotic membrane bioreactors (OMBRs) have been applied to enhance removal of antibiotics, however, information on the effects of molecular structures on the behavior of antibiotics is still lacking. Herein, adsorption kinetics, transformation pathways, and membrane rejection mechanisms of OMBRs were investigated by adding two typical antibiotics (i.e., sulfadiazine, SDZ, and tetracycline hydrochloride, TC-HCl). 80.70-91.12% of TC-HCl was removed by adsorption and biodegradation, while 17.50-75.14% of SDZ was removed by membrane rejection; this depended on its concentration due to reduced electrostatic interactions and hydrophobic adsorption. The adsorption capacity of TC-HCl (i.e., 1.34±0.01 mg/g) was significantly higher than that of SDZ (i.e., 0.18±0.03 mg/g) due to enhanced π-π interactions, hydrogen bonding and improved electrostatic interactions. The abundant production of polysaccharide-like substances from TC-HCl biodegradation contributed to microbial metabolism and thus enhanced microbial function during TC-HCl biotransformation. The primary degradation pathways were determined by microbial function analysis, and the primary intermediates from TC-HCl degradation were less toxic than those from SDZ degradation due to the different reactions of amino groups. These results and the corresponding mechanism provide a theoretical foundation for the further development of OMBR technology for highly efficient treatment of antibiotic wastewater.

15.
FEBS J ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34492154

RESUMO

The migrasome is a newly discovered organelle produced by migrating cells. As cells migrate, long and thin retraction fibers are left in their wake. On these fibers, we discovered the production of a pomegranate-like structure, which we named migrasomes. The production of migrasomes is highly correlated with the migration of cells. Currently, it has been demonstrated the migrasomes exhibit three modes of action: release of signaling molecules through rupturing or leaking, carriers of damaged mitochondria, and lateral transfer of mRNA or proteins. In this review, we would like to discuss, in detail, the functions, mechanisms, and potential applications of this newly discovered cell organelle.

16.
Asian J Androl ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34494557

RESUMO

This study explored the usefulness of two-dimensional shear wave elastography (2D-SWE) in the early assessment of corpora cavernosa fibrosis (CCF). New Zealand male rabbits were randomly assigned to an experimental group or a control group. Recombinant human transforming growth factor beta 1 (TGF-ß1) was injected into the dorsal penis tissue of rabbits in the experimental group. Conventional ultrasound and 2D-SWE examinations were performed before and 20 days after injection. Penile histological analysis was performed by hematoxylin-eosin staining, sirius red staining, and immunohistochemistry. Measurement of 2D-SWE examination results was performed using shear wave elastography quantitative measurement (SWQ). Histological analysis outcomes were the proportion of smooth muscle cells (SMCs), collagen fibers (CFs), collagen type I (Col I), and collagen type III (Col III), as well as the SMCs/CFs ratio, measured by sirius red staining. Other histological analysis outcomes were the positive area proportion (PAP) of TGF-ß1 (PAPT), fibronectin (PAPF), and Col III (PAPC), measured by immunohistochemistry. After recombinant human TGF-ß1 injection, SWQ was higher in the experimental group than that in the control group (P < 0.001); however, there were no differences in conventional ultrasound results. There were significant differences in histological outcomes between the two groups (all P < 0.05). These results indicated that 2D-SWE was superior for identifying early histological changes in CCF.

17.
Artigo em Inglês | MEDLINE | ID: mdl-34495458

RESUMO

BACKGROUND AND OBJECTIVE: Entrectinib is a selective inhibitor of ROS1/TRK/ALK kinases, recently approved for oncology indications. Entrectinib is predominantly cleared by cytochrome P450 (CYP) 3A4, and modulation of CYP3A enzyme activity profoundly alters the pharmacokinetics of both entrectinib and its active metabolite M5. We describe development of a combined physiologically based pharmacokinetic (PBPK) model for entrectinib and M5 to support dosing recommendations when entrectinib is co-administered with CYP3A4 inhibitors or inducers. METHODS: A PBPK model was established in Simcyp® Simulator. The initial model based on in vitro-in vivo extrapolation was refined using sensitivity analysis and non-linear mixed effects modeling to optimize parameter estimates and to improve model fit to data from a clinical drug-drug interaction study with the strong CYP3A4 inhibitor, itraconazole. The model was subsequently qualified against clinical data, and the final qualified model used to simulate the effects of moderate to strong CYP3A4 inhibitors and inducers on entrectinib and M5 pharmacokinetics. RESULTS: The final model showed good predictive performance for entrectinib and M5, meeting commonly used predictive performance acceptance criteria in each case. The model predicted that co-administration of various moderate CYP3A4 inhibitors (verapamil, erythromycin, clarithromycin, fluconazole, and diltiazem) would result in an average increase in entrectinib exposure between 2.2- and 3.1-fold, with corresponding average increases for M5 of approximately 2-fold. Co-administration of moderate CYP3A4 inducers (efavirenz, carbamazepine, phenytoin) was predicted to result in an average decrease in entrectinib exposure between 45 and 79%, with corresponding average decreases for M5 of approximately 50%. CONCLUSIONS: The model simulations were used to derive dosing recommendations for co-administering entrectinib with CYP3A4 inhibitors or inducers. PBPK modeling has been used in lieu of clinical studies to enable regulatory decision-making.

18.
BMC Pulm Med ; 21(1): 284, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488706

RESUMO

PURPOSE: To investigate the changes of cough sensitivity in patients with metabolic syndrome and its possible mechanisms. METHOD: A total of 29 metabolic syndrome (MetS) patients with OSAHS (group-1), 22 MetS patients without OSAHS (group-2), and 25 healthy controls (group-3) were included. All participants underwent a routine physical examination and completed the gastroesophageal reflux disease questionnaire (GerdQ), and the inflammatory mediator profile were determined. The cough threshold for capsaicin, induced sputum cell count and cell classification, and inflammatory mediators in induced sputum supernatants were compared. The correlation between capsaicin cough sensitivity and various indicators in the MetS population was analyzed. RESULTS: The minimum concentration of inhaled capsaicin needed to induce ≥ 5 coughs (C5) was significantly different among three groups (H = 14.393, P = 0.001) and lower for group-1 and group-2 than it for group-3 (P = 0.002, P = 0.005). The percentage of neutrophils in induced sputum and the concentrations of calcitonin gene-related peptide (CGRP), substance P (SP), and interleukin 8 (IL-8) in the sputum supernatant of group-1 and group-2 were significantly higher than those of group-3. Besides, the pepsin concentrations were significantly different among the 3 groups (F = 129.362, P < 0.001), which significantly was highest in group-1 (P < 0.001) and lowest in group-3 (P < 0.001). Triglycerides, AHI, pepsin concentration and BMI were risk factors of increased capsaicin cough sensitivity. CONCLUSION: Increased capsaicin cough sensitivity in MetS patients is closely related to sleep apnea and gastroesophageal reflux. For patients in MetS patients without OSAHS, gastroesophageal reflux is an important factor for increased capsaicin cough sensitivity. Airway inflammation, especially airway neurogenic inflammation, may also play a role in the pathogenesis of increased capsaicin cough sensitivity. Trial registration The protocol was registered in the Chinese Clinical Trials Register ( http://www.chictr.org.cn/ ) (ChiCTR1800014768). Written informed consent was obtained from all participants before enrollment.

19.
Scand J Gastroenterol ; : 1-7, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34499844

RESUMO

OBJECTIVES: To determine the predictors of difficult colorectal endoscopic submucosal dissection (ESD) and to develop a preoperative predictive model for difficult colorectal ESD procedures. METHODS: Colorectal neoplasms intended to be resected by ESD in our center between August 2013 and February 2019 were retrospectively enrolled. An ESD procedure which took more than 30 min, failed to remove the lesions en bloc or converted to surgery was defined as difficulty. Logistic regression analysis was conducted to find out the predictors of difficult ESD. A nomogram integrating independent predictors was developed and validated with respect to its discrimination, calibration and clinical application, using the receiver operating characteristic (ROC) curve, calibration plot and decision curve analysis (DCA), respectively. RESULTS: A total of 368 colorectal neoplasms in 355 patients were included. The independent predictors for difficult colorectal ESD were size ≥2 cm (odds ratio [OR] = 6.102, p < .001), positive non-lifting sign (OR = 6.569, p = .005), lesions located in left colon (OR = 2.475, p = .036) or rectum (OR = 2.183, p = .048), laterally spreading tumors (LSTs) (OR = 2.501, p = .008) and less colorectal ESD experience (≤20 cases) (OR = 2.3091, p = .028). The nomogram model incorporating the above predictors performed well in both of the training and validation sets (area under the cure [AUC] = 0.786 and 0.784, respectively). DCA demonstrated the clinical benefit of the nomogram was superior to that of each independent predictor alone. CONCLUSIONS: The nomogram incorporating tumor size, location, morphology, non-lifting sign and ESD experience of operator can be conveniently used to facilitate the preoperative prediction of difficult colorectal ESD.

20.
Front Immunol ; 12: 683595, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484181

RESUMO

Background: Previous trials demonstrated evidence involving the total effects of gemtuzumab ozogamicin (GO), an anti-CD33 humanized antibody, on treating acute myeloid leukemia (AML). In this updated systematic review, meta-analysis, and network meta-analysis (NMA), we aimed to comprehensively explore the clinical benefits and safety of GO in various subtypes of AML. Methods: PubMed, Embase, Cochrane, and Chinese databases were filtered to search randomized controlled trials (RCTs) and retrospective cohort studies that compared clinical efficiency and toxicity of GO with non-GO groups in AML. Random-effects models were used to calculate pooled effect sizes and 95% confidence intervals (CIs). Relative risk (RR) was used for estimating complete remission (CR), early death, and toxicity. Hazard risk (HR) was accomplished to evaluate survival. Results: Fifteen RCTs and 15 retrospective cohort studies were identified (GO: 4,768; Control: 6,466). GO tended to improve CR (RR 0.95, p = 0.084), followed by significantly improved survival (overall survival: HR 0.86, p = 0.003; event-free survival: HR 0.86, p = 0.015; relapse-free survival: HR 0.83, p = 0.001; cumulative incidence of relapse: HR 0.82, p < 0.001). GO benefits of CR and survival were evident in favorable- and intermediate-risk karyotypes (p ≤ 0.023). GO advantages were also associated with nucleophosmin 1 mutations (p ≤ 0.04), wild-type FMS-like tyrosine kinase 3 internal tandem duplication gene (p ≤ 0.03), age of <70 years (p < 0.05), de novo AML (p ≤ 0.017), and CD33(+) (p ≤ 0.021). Both adding GO into induction therapy (p ≤ 0.011) and a lower (<6 mg/m2) dose of GO (p ≤ 0.03) enhanced survival. Prognosis of combined regimens with GO was heterogeneous in both meta-analysis and NMA, with several binding strategies showing improved prognosis. Additionally, GO was related to increased risk of early death at a higher dose (≥6 mg/m2) (RR 2.01, p = 0.005), hepatic-related adverse effects (RR 1.29, p = 0.02), and a tendency of higher risk for hepatic veno-occlusive disease or sinusoidal obstruction syndrome (RR 1.56, p = 0.072). Conclusions: These data indicated therapeutic benefits and safety of GO in AML, especially in some subtypes, for which further head-to-head RCTs are warranted. Systematic Review Registration: [PROSPERO: https://www.crd.york.ac.uk/prospero/], identifier [CRD42020158540].

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