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1.
J Hazard Mater ; 442: 130138, 2023 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-36303360

RESUMO

Exogenous microparticles including microplastics are novel pollutants that could persist in the environment with potential health effects, while crucial data on their exposure in humans are still lacking. To understand the panorama of microparticles including microplastics exposure and distribution characteristics in different kinds of body fluids. A non-targeted microparticle internal exposure landscape analysis was done in thirteen kinds of human enclosed body fluids covering eight body systems. Totally 104 patients aged 24-96 years with an average age of 56 years were included in this study. After sample digestion, non-soluble microparticles were detected and identified with one Raman Microspectroscope under a strict quality control-particle detection system. Totally 702 microparticles with size ranging from 2.15 to 103.27 µm were detected in samples. Microparticles were identified into 84 substances or 66 molecules, most of which were firstly reported inside human body. Nine kinds of microplastics were originally reported in human body fluids with their size ranging from 19.66 to 103.27 µm. Microparticles exposure was unexpectedly high inside the human body despite the protection of biological barriers and membranes, raising awareness of the impact of particle pollution on sustainable development.


Assuntos
Líquidos Corporais , Poluentes Químicos da Água , Humanos , Pessoa de Meia-Idade , Microplásticos , Plásticos/análise , Poluentes Químicos da Água/análise , Poluição Ambiental , Líquidos Corporais/química , Monitoramento Ambiental
2.
J Hazard Mater ; 443(Pt A): 130159, 2023 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-36283218

RESUMO

Tritium is the main component of radioactive wastewater from nuclear power plants and can be migrated into organisms to form organically bound tritium (OBT), which may pose a potential risk to aquatic ecosystem. Hence, it is essential to monitor OBT conversion in the presence of tritium exposure. In this study, the effects of pretreatment methods such as digestion on the recovery of tritium were discussed. It was found that microwave digestion pretreatment could improve the recovery of tritium by up to 90 % and allow OBT measurement with a small sample size equivalent to about 60 mg (dry weight). In addition, the efficiency of OBT transformation was different among biological samples, and the radiation hormesis phenomenon was induced by tritium exposure (3.7 × 106 Bq/L) in microalgae Chlorella vulgaris(C. vulgaris). The tritium exposure may induce radiation hormesis through the reactive oxygen species (ROS) signaling pathway, thus improving the photosynthetic capacity and metabolism level of C. vulgaris. Furthermore, enhancement of photorespiration metabolism and the antioxidation system may be important means for C. vulgaris to balance damage by tritium radiation. This study provides insights for further investigating OBT behavior, and will contribute to understanding the equilibrium damage mechanism of algae exposed to tritium.


Assuntos
Chlorella vulgaris , Monitoramento de Radiação , Trítio , Espécies Reativas de Oxigênio , Monitoramento de Radiação/métodos , Ecossistema , Hormese , Chlorella vulgaris/metabolismo , Transdução de Sinais
3.
Neural Regen Res ; 18(2): 451-455, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35900445

RESUMO

Methylprednisolone pulse treatment is currently used for optic neuritis. It can speed visual recovery, but does not improve the ultimate visual outcomes. Recent studies have reported that miR-125a-5p has immunomodulatory effects on autoimmune diseases. However, it remains unclear whether miR-125a-5p has effects on optic neuritis. In this study, we used adeno-associated virus to overexpress or silence miR-125a-5p in mice. We found that silencing miR-125a-5p increased the latency of visual evoked potential and aggravated inflammation of the optic nerve. Overexpression of miR-125a-5p suppressed inflammation of the optic nerve, protected retinal ganglion cells, and increased the percentage of Treg cells. Our findings show that miR-125a-5p exhibits anti-inflammatory effects through promoting the differentiation of Treg cells.

4.
Am J Otolaryngol ; 44(1): 103548, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36283163

RESUMO

PURPOSE: To perform a systematic review and meta-analysis of clinical studies exploring the association between antenatal corticosteroids exposure and hearing loss in preterm infants. METHOD: PubMed, Cochrane library, and EMBASE databases from the inception dates to December 22, 2020 without language restriction. Key search terms included hearing loss, cortisol steroid, and antenatal. Included studies were case control or cohort studies examining preterm (<37 weeks' gestation) or very low-birth-weight (<1500 g) infants and reporting primary data that could be used to explore the association between antenatal corticosteroids exposure and the development of hearing outcomes. This meta-analysis follows the reporting guidelines (MOOSE) for observational studies. Data were independently extracted by 2 researchers. A fixed effects model was used to calculate odds ratios (OR) and 95 % CI. Subgroup analysis was conducted according to different types of antenatal steroids exposure (dexamethasone vs betamethasone) and subgroup analyses based on betamethasone and betamethasone combined with magnesium sulfate (betamethasone vs betamethasone combined with magnesium sulfate). RESULTS: A total of 110 potentially relevant studies were found, of which 7 met the inclusion criteria (A total of 8130 preterm infants were included. 5337 preterm infants were exposed to antenatal corticosteroids, and 2793 preterm infants were not exposed to antenatal corticosteroids.). Meta-analysis showed that antenatal corticosteroids exposure was significantly associated with hearing loss in preterm infants. (OR, 0.64; 95 % CI, 0.48-0.87; P = 0.004) In addition, significant differences were found between antenatal betamethasone exposure and antenatal dexamethasone exposure. (OR, 0.27; 95 % CI, 0.10-0.77; P = 0.01) Betamethasone and betamethasone combined with magnesium sulfate showed that the difference was no statistically significant. (OR, 1.34; 95 % CI, 0.74-2.43; P = 0.33). CONCLUSION: The results of this study confirm that among preterm infants, exposure to antenatal corticosteroids exposure is associated with a lower risk of developing hearing impairment. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO 2021 CRD42021255665.


Assuntos
Surdez , Perda Auditiva , Síndrome do Desconforto Respiratório do Recém-Nascido , Recém-Nascido , Humanos , Feminino , Gravidez , Recém-Nascido Prematuro , Sulfato de Magnésio , Corticosteroides/efeitos adversos , Betametasona/efeitos adversos , Perda Auditiva/induzido quimicamente , Perda Auditiva/epidemiologia , Perda Auditiva/prevenção & controle , Dexametasona/efeitos adversos , Estudos Observacionais como Assunto
5.
Food Chem ; 404(Pt A): 134382, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36252371

RESUMO

Fuzhuan brick tea (FBT) is a post-fermented dark tea preferred by consumers for its excellent hypolipidemic activity, and theabrownin (TB) is the main bioactive composition in FBT. This work explored the structural and hypolipidemic properties of TB derived from Pingwu FBT, and investigated whether it exerted hypolipidemic activity by inhibiting intestinal lipid absorption. Structural characterization revealed that TB was an amorphous polymerized phenolic compound rich in hydroxyl and carboxyl groups with good thermostability. In vivo, TB and its fractions with different molecular weights (TB-LT3k, TB-3-10k, TB-10-30k, TB-30-100k, TB-GT100k) significantly reduced the lipid levels of hyperlipidemia zebrafish (P < 0.05). Moreover, TB attenuated hyperlipidemia by inhibiting intestinal lipid absorption, as TB effectively bound to bile acids, inhibited enzymatic activity of pancreatic lipase and cholesterol esterase, influenced micelle formation, and decreased micellar cholesterol solubility. Results facilitated research on TB and offered support for its feasibility as a natural alternative to prevent hyperlipidemia.


Assuntos
Hiperlipidemias , Doenças Metabólicas , Animais , Chá/química , Peixe-Zebra , Hiperlipidemias/tratamento farmacológico , Digestão , Lipídeos
6.
Front Microbiol ; 13: 962507, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36452932

RESUMO

Polymyxin A1 was a rarely investigated member in the polymyxins family produced by Bacillus aerosporus. As a cyclic non-ribosomal lipopeptide, it was purified from Paenibacillus thiaminolyticus for the first time. The producing strain SY20 was screened from Chinese natural fermented bamboo shoots and identified as P. thiaminolyticus SY20 using 16S rRNA homology along with whole genome sequencing. The optimum incubation time was 32 h by the growth kinetics of antimicrobial agent production. The proteinaceous nature of antimicrobial agents was characterized according to the physicochemical properties of the cell-free supernatant. Subsequently, the active antimicrobial agent was purified from the supernatant using ammonium sulfate-graded precipitation, ion-exchange chromatography, and C18-H chromatography. The active agent was identified as polymyxin A1 with a molecular weight 1156.7 Da and antimicrobial activity mainly against Gram-negative bacteria. The molecular structure, a cyclic heptapeptide and a tripeptide side chain acylated by a fatty acid at the amino terminus, was elucidated using the combination of liquid chromatography-tandem mass spectrometry (LC-MS/MS), matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), amino acid analysis, and whole genome mining tool. Meanwhile, the biosynthetic gene cluster of polymyxin A1 including five open reading frames (ORFs) was demonstrated in the genome. The compound should be further explored for its efficacy and toxicity in vivo to develop its application.

7.
Interv Neuroradiol ; : 15910199221143168, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36457291

RESUMO

BACKGROUND: Digital subtraction angiography (DSA) is most commonly used in vessel disease examinations and treatments. We aimed to develop a novel deep learning-based method to deblur the large focal spot DSA images, so as to obtain a clearer and sharper cerebrovascular DSA image. METHODS: The proposed network cascaded several residual dense blocks (RDBs), which contain dense connected layers and local residual learning. Several loss functions for image restoration were investigated. Our training set consisted of 52 paired images of angiography with more than 350,000 cropped patches. The testing set included 10 body phantoms and 80 clinical images of different types of diseases for subjective evaluation. All test images were acquired using a large focal spot, and phantom images were simultaneously acquired using a micro focal spot as ground-truth. Peak-to-noise ratio (PSNR) and structural similarity (SSIM) were determined for quantitative analysis. The deblurring results were compared with the original data, and the image quality was subjectively evaluated and graded by two clinicians. RESULTS: For quantitative analysis of phantom images, the average PSNR/SSIM based on the deep-learning approach (35.34/0.9566) was better than that of large focal spot images (30.64/0.9163). For subjective evaluation of 80 clinical patient images, image quality in all types of cerebrovascular diseases was also improved based on a deep-learning approach (p < 0.001). CONCLUSIONS: Deep learning-based focal spot deblur algorithm can efficiently improve DSA image quality for better visualization of blood vessels and lesions in the image.

8.
Clin Exp Nephrol ; 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36469196

RESUMO

BACKGROUND: Some clinical trials have shown that soluble urokinase-type plasminogen activator receptor (suPAR) has good predictive value for acute kidney injury (AKI), but there is still a lack of evidence-based proof. Therefore, we conducted this systematic review and meta-analysis to evaluate the predictive value of suPAR for AKI. METHODS: Pubmed, EMBASE, Cochrane Library, and Web of Science databases were searched until December 2021 to obtain the literature on the prediction of suPAR for AKI. The quality of the included studies was assessed using the QUADAS-2 scoring system, and a bivariate random-effect model was used for the meta-analysis. The present study has been registered on PROSPERO (Registration No. CRD42022324978). RESULTS: Seven articles were included, involving 2,319 patients, 635 of whom were AKI patients. The meta-analysis results showed that the combined sensitivity of suPAR in predicting AKI was 0.77 (95% CI 0.67-0.84); the specificity was 0.64 (95% CI 0.53-0.75); the odds ratio of diagnosis was 6 (95% CI 3-10); the pooled positive likelihood ratio was 2.2 (95% CI 1.6-2.9); the pooled negative likelihood ratio was 0.36 (95% CI 0.26-0.52); and the area under the summary receiver-operating characteristic (SROC) curve was 0.77 (95% CI 0.12~0.99). Deek's funnel plot suggested no potential publication bias among included studies. CONCLUSION: suPAR is a valuable biomarker for the prediction of AKI with relatively high predictive accuracy, but its clinical application needs improvements. SuPAR should be considered as an indicator in the subsequent development of more effective predictive tools for AKI.

9.
Front Endocrinol (Lausanne) ; 13: 1036517, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36465633

RESUMO

Human fetal adrenal glands produce substantial amounts of dehydroepiandrosterone (DHEA), which is one of the most important precursors of sex hormones. However, the underlying biological mechanism remains largely unknown. Herein, we sequenced human fetal adrenal glands and gonads from 7 to 14 gestational weeks (GW) via 10× Genomics single-cell transcriptome techniques, reconstructed their location information by spatial transcriptomics. Relative to gonads, adrenal glands begin to synthesize steroids early. The coordination among steroidogenic cells and multiple non-steroidogenic cells promotes adrenal cortex construction and steroid synthesis. Notably, during the window of sexual differentiation (8-12 GW), key enzyme gene expression shifts to accelerate DHEA synthesis in males and cortisol synthesis in females. Our research highlights the robustness of the action of fetal adrenal glands on gonads to modify the process of sexual differentiation.


Assuntos
Feto , Gônadas , Feminino , Masculino , Humanos , Diferenciação Sexual , Glândulas Suprarrenais , Desidroepiandrosterona
10.
Front Neurol ; 13: 1049806, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36468053

RESUMO

Background: A convergence of research supports a key role of the vestibular system in visuospatial ability. However, visuospatial ability may decline with age. This work aims to elucidate the important contribution of vestibular function to visuospatial ability in old adults through a computerized test system. Methods: Patients with a clinical history of recurrent vertigo and at least failed one vestibular test were included in this cross-sectional study. Healthy controls of three age groups: older, middle-aged, and young adults were also involved. Visuospatial cognitive outcomes including spatial memory, spatial navigation, and mental rotation of all the groups were recorded. Comparing the performance of the visuospatial abilities between patients and age-matched controls as well as within the controls. Results: A total of 158 individuals were enrolled. Results showed that patients performed worse than the age-matched controls, with the differences in the forward span (p < 0.001), the time of the maze 8 × 8 (p = 0.009), and the time of the maze 12 × 12 (p = 0.032) being significant. For the differences in visuospatial cognitive outcomes within the controls, the younger group had a significantly better performance than the other groups. The older group and the middle-aged group had comparable performances during all the tests. Conclusions: Older patients with vestibular dysfunction had more difficulties during visuospatial tasks than age-matched controls, especially in spatial memory and spatial navigation. Within the controls, younger adults did much better than other age groups, while older adults behaved similarly to middle-aged adults. It is a valuable attempt to computerize the administration of tests for visuospatial ability.

11.
Gerontology ; : 1-22, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36470214

RESUMO

INTRODUCTION: Senile osteoporosis is one of the most common age-related diseases worldwide. Glucagon like peptide-2 (GLP-2), a naturally occurring gastrointestinal peptide, possesses therapeutic effects on bone loss in postmenopausal women and ovariectomized rats. However, the role of GLP-2 in senile osteoporosis and underlying mechanisms has not been explored. METHODS: GLP-2 was subcutaneously injected into the 6-month-old male senile osteoporosis model of senescence-accelerated mouse prone 6 (SAMP6) mice for 6 weeks. SAMP6 subjected to normal saline and senescence-accelerated mouse resistant 1 served as control groups. Micro-computed tomography was performed to evaluate the bone mass and microarchitecture of the mice. Osteoblastic and osteoclastic activities were determined by biochemical, quantitative real-time PCR, histological, and histomorphometric analyses combined with hematoxylin-eosin, toluidine blue, and tartrate-resistant acid phosphatase staining. We also examined the proteins and structure of intestinal tight junction using immunohistochemical assay as well as a transmission electron microscope. Serum inflammation marker levels were measured using ELISA. Additionally, anti-oxidative enzymes GPX-4 and SOD-2 and receptors of GLP-2 and vitamin D expression in the ileum and colon were detected under immunofluorescence staining. RESULTS: Six-week GLP-2 treatment attenuated bone loss in SAMP6 mice, as evidenced by increased bone mineral density, improved microarchitecture in femora, and enhanced osteogenic activities. In contrast, the activity of osteoclastic activity was not obviously inhibited. Moreover, GLP-2 ameliorated tight junction structure and protein expression in the intestinal barrier, which was accompanied by the reduction of TNF-α level. The expression of receptors of intestinal GLP-2 and vitamin D in the ileum was elevated. Furthermore, the oxidative stress in the intestines was improved by increasing the GPX-4 and SOD-2 signaling. CONCLUSION: Our findings suggest that GLP-2 could ameliorate age-associated bone loss, tight junction structure, and improved antioxidant enzyme activity in the gut in SAMP6 mice. Amelioration of gut barrier dysfunction may potentially contribute to improving bone formation and provide evidence for targeting the entero-bone axis in the treatment of senile osteoporosis.

12.
Zhongguo Zhong Yao Za Zhi ; 47(22): 6097-6116, 2022 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-36471935

RESUMO

In this study, UPLC-Q-Exactive-MS/MS was used to rapidly analyze the chemical constituents of Meconopsis quintupli-nervia, and the anti-liver fibrosis mechanism of M. quintuplinervia was preliminarily analyzed by network pharmacology, molecular docking, and cell experiments. The chemical constituents of M. quintuplinervia were identified according to the information of MS~1 and MS~2, as well as the data in the literature and databases. SwissTargetPrediction and TargetNet were used to predict the potential targets. The targets related to liver fibrosis were collected from GeneCards and OMIM. The protein-protein interaction(PPI) network was constructed by STRING. Cytoscape 3.6.1 was used to construct and analyze the "constituent-target-disease" network to obtain key targets and their corresponding constituents in the network. DAVID 6.8 was used for GO analysis and KEGG signaling pathway enrichment analysis. Finally, the preliminary verification was carried out by molecular docking and cell experiments. As a result, 106 chemical constituents were identified from M. quintuplinervia, including 66 flavonoids, 16 alkaloids, 18 phenolic acids, 1 anthocyanin, and 5 other constituents. Among them, 3 constituents were identified as potential new compounds, and 59 constituents were reported in M. quintuplinervia for the first time. Network pharmacology analysis showed that M. quintuplinervia presumably acted on AKT1, SRC, JUN, EGFR, STAT3, HSP90 AA1, MAPK3, and other core targets through luteolin, isorhamnetin, quercetin, apigenin, kaempferide, amurine, 2-methylflavinantine, allocryptopine, the multi and other active compounds, thereby regulating the PI3 K/AKT signaling pathway, pathways in cancer, proteoglycans in cancer, FoxO signaling pathway, and other pathways to exert anti-liver fibrosis effects. M. quintuplinervia extract(MQE) could significantly down-regulate PI3 K and AKT protein levels in the HSC-T6 cell model induced by TGF-ß1, suggesting that MQE may have the ability to regulate the PI3 K/AKT signaling pathway. The findings of this study indicated that the anti-liver fibrosis effect of M. quintuplinervia had multi-constituent, multi-target, and multi-pathway characteristics, which may provide a scientific basis for the research on the pharmacodynamic materials, action mechanism, and quality markers of M. quintupli-nervia.

13.
World J Surg Oncol ; 20(1): 381, 2022 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-36464702

RESUMO

BACKGROUND: An increasing number of studies have shown that microRNAs play an important role in the occurrence and development of small cell lung cancer, which mainly manifest as oncogenic and tumor inhibition. Therefore, microRNAs may affect the survival of patients with small cell lung cancer. In this meta-analysis, we will evaluate the role of microRNAs in the overall survival of patients with small cell lung cancer, which may provide valuable information for the treatment of small cell lung cancer. METHODS: We searched the PubMed, Embase, and Web of Science online databases to determine the effect of microRNAs on the prognosis of patients with small cell lung cancer. The data and characteristics of each study were extracted, and the hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to estimate the effect. RESULTS: A total of 7 articles, involving 427 subjects and 15 studies, were included in this meta-analysis. The pooled HR of the relationship between the microRNA expression level and the overall survival rate of small cell lung cancer patients was 1.25 (95% CI: 1.06-1.47). There was a significant difference in the prognostic value of oncogenic and tumor inhibition microRNAs among patients with small cell lung cancer, with pooled HRs of 1.60 (95% CI: 1.35-1.90) and 0.42 (95% CI: 0.30-0.57), respectively. CONCLUSIONS: MicroRNAs have a significant impact on the overall survival of small cell lung cancer patients, suggesting that microRNAs can be used as potential prognostic markers and may provide treatment strategies for small cell lung cancer patients. TRIAL REGISTRATION: The protocol was registered on PROSPERO website with the registration number of CRD42022334363. The relevant registration information can be obtained from the website https://www.crd.york.ac.uk/prospero/#searchadvanced .


Assuntos
Neoplasias Pulmonares , MicroRNAs , Carcinoma de Pequenas Células do Pulmão , Humanos , MicroRNAs/genética , Prognóstico , Carcinoma de Pequenas Células do Pulmão/genética , Carcinogênese , Neoplasias Pulmonares/genética
14.
Artigo em Inglês | MEDLINE | ID: mdl-36337584

RESUMO

Constipation is one of the most common nonmotor symptoms in patients with Parkinson's disease (PD) and often occurs before motor symptoms. Electroacupuncture effectively improves the symptoms of constipation in patients with PD. In the present study, we used thymus cell antigen 1-α-synuclein (Thy1-αSyn) transgenic mice as a model of intestinal motility disorders in PD to determine the therapeutic effect of electroacupuncture and the underlying mechanisms. Electroacupuncture significantly improved fecal excretion and accelerated the rate of small-intestinal propulsion in Thy1-αSyn mice by upregulating the serotonin concentration and the expression of the serotonin 4 receptor. Consequently, the downstream cyclic AMP/protein kinase A (cAMP/PKA) pathway was affected, and to upregulate and downregulate, the expression of substance P was upregulated, and the expression of calcitonin gene-related peptide was downregulated. In summary, electroacupuncture improved intestinal motility in PD mice by affecting serotonin levels, serotonin 4 receptor expression, and the cAMP/PKA pathway, providing a potentially effective and promising complementary and alternative therapy for relieving constipation symptoms in patients with PD.

15.
Regen Biomater ; 9: rbac079, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338176

RESUMO

The occurrence of various liver diseases can lead to organ failure of the liver, which is one of the leading causes of mortality worldwide. Liver tissue engineering see the potential for replacing liver transplantation and drug toxicity studies facing donor shortages. The basic elements in liver tissue engineering are cells and biomaterials. Both mature hepatocytes and differentiated stem cells can be used as the main source of cells to construct spheroids and organoids, achieving improved cell function. To mimic the extracellular matrix (ECM) environment, biomaterials need to be biocompatible and bioactive, which also help support cell proliferation and differentiation and allow ECM deposition and vascularized structures formation. In addition, advanced manufacturing approaches are required to construct the extracellular microenvironment, and it has been proved that the structured three-dimensional culture system can help to improve the activity of hepatocytes and the characterization of specific proteins. In summary, we review biomaterials for liver tissue engineering, including natural hydrogels and synthetic polymers, and advanced processing techniques for building vascularized microenvironments, including bioassembly, bioprinting and microfluidic methods. We then summarize the application fields including transplant and regeneration, disease models and drug cytotoxicity analysis. In the end, we put the challenges and prospects of vascularized liver tissue engineering.

16.
J Dig Dis ; 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36326787

RESUMO

BACKGROUND AND OBJECTIVE: Systemic inflammatory responses are common in patients with chronic severe hepatitis (CSH) and increase their risk of mortality. Knowledge regarding the impact of the systemic inflammatory response on short-term outcomes in noncirrhotic CSH patients is limited. PATIENTS AND METHODS: We collected data from two prospective, multicenter cohorts from the CATCH-LIFE non-cirrhotic cohort. Cox regression was used to explore the association between systemic inflammation markers and 90-day liver transplant (LT)-free mortality. Generalized additive model (GAM) was used to illustrate the quantitative curve relationship between the neutrophil-to-lymphocyte ratio (NLR) and 90-day LT-free mortality. Kaplan-Meier methods were used to estimate the 90-year LT-free survival rates. RESULTS: The prevalence of CSH in the CATCH-LIFE study was 20.5% (226/1103). The 28-day and 90-day LT-free mortality rates were 17.7% and 26.1%, respectively. Noninfected patients accounted for 75% of CSH patients, and the NLR was independently associated with 90-day LT-free mortality. Quantitative analysis of the association between the NLR and 90-day LT-free mortality showed that an NLR of 2.9 may represent the starting point for disease deterioration in CSH patients without infection. CONCLUSIONS: This study identified the NLR as an independent risk factor for 90-day LT-free mortality in noncirrhotic CLD patients. The NLR can better indicate the systemic inflammatory response in noninfected CSH patients. An NLR of 2.9 may be the cutoff for disease aggravation onset in CSH patients without infection.

17.
Artigo em Inglês | MEDLINE | ID: mdl-36357265

RESUMO

PURPOSE: To understand the epidemiological characteristics of nosocomial infection of carbapenem-resistant Enterobacteriaceae (CRE) in an urban medical union includes 10 medical hospitals with different number of beds in China. METHODS: Epidemiological data on age, department, and infection of CRE cases detected from January 2014 to December 2021 were collected via a real-time hospital-infection monitoring system or manually for subsequent characterization. A multi-departmental and multi-disciplinary matrix (MMM) management of CRE was established and implemented within a medical union. RESULTS: A total of 1327 cases of CRE infection were detected during the 8 years, of which 352 were due to nosocomial infection, with an infection morbidity of 0.046% and a resistance rate of 10.79%. The morbidity of CRE infection showed a trend of year-to-year fluctuation. The morbidity of CRE infection was significantly higher in winter and spring than that in summer and autumn, significantly higher in men than in women (χ2 â€‹= â€‹55.891, p â€‹< â€‹0.001), and 3 times higher in elderly patients ≥65 years old than in patients <65 years old (χ2 â€‹= â€‹117.517, p â€‹< â€‹0.001). The morbidity of CRE infection after intervention with MMM management decreased significantly from 0.071% to 0.042% (χ2 â€‹= â€‹15.628, p â€‹< â€‹0.001). CONCLUSIONS: CRE prevention and control practice should be adapted to seasonal variations, gender and age differences. The effective prevention and control of CRE nosocomial infections can be achieved by implementing MMM management within a medical association.

18.
Artigo em Inglês | MEDLINE | ID: mdl-36350322

RESUMO

Purpose: Our study aims to investigate the long-term survival and prognostic factors of patients after laparoscopic radical nephrectomy. Methods: Totally, 245 patients with renal cell carcinoma in our hospital from January 2015 to February 2017 were analyzed retrospectively. The 5-year survival status of patients with renal cell carcinoma was under analysis and further based on univariate analysis, and its influencing factors were analyzed by Cox regression. Results: The average 5-year follow-up time of 245 patients with renal cell carcinoma was (4.88 ± 0.52) years. The mortality of 1 year, 3 years and 5 years were 2.45% (5/245), 6.35% (16/245) and 9.80% (24/245), respectively. The survival rates were 97.55% (239/245), 93.06% (228/245) and 90.61% (222/245). Univariate analysis showed that age, tumor diameter, hematuria, TNM stage and postoperative recurrence may be the influencing factors of 5-year survival of patients with renal cell carcinoma (P < .05). However, the following parameters, including gender, course of disease, and other clinical complications were not related to the 5-year survival of patients with renal cell carcinoma (P > .05). the influencing factors of 5-year survival status of patients with renal cell carcinoma were age, tumor diameter, hematuria, TNM stage, and postoperative recurrence. Conclusion: The study revealed the long-term survival of patients with renal cell carcinoma may be associated with age, tumor diameter, hematuria, TNM stage and postoperative recurrence.

19.
PLoS One ; 17(11): e0277251, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36331958

RESUMO

GPR40, a G protein-coupled receptor for free fatty acids (FFAs), is considered as a therapeutic target for type 2 diabetes mellitus (T2DM) since GPR40 activation in pancreatic beta cells enhances glucose-stimulated insulin secretion. Nonalcoholic fatty liver disease (NAFLD) is a common complication of T2DM or metabolic syndrome (MetS). However, the role of GPR40 in NAFLD associated with T2DM or MetS has not been well established. Given that it is known that cholesterol and FFAs are critically involved in the pathogenesis of nonalcoholic steatohepatitis (NASH) and LDL receptor (LDLR)-deficient mice are a good animal model for human hyperlipidemia including high cholesterol and FFAs, we generated GPR40 and LDLR double knockout (KO) mice in this study to determine the effect of GPR40 KO on hyperlipidemia-promoted NASH. We showed that GPR40 KO increased plasma levels of cholesterol and FFAs in high-fat diet (HFD)-fed LDLR-deficient mice. We also showed that GPR40 KO exacerbated HFD-induced hepatic steatosis, inflammation and fibrosis. Further study demonstrated that GPR40 KO led to upregulation of hepatic CD36 and genes involved in lipogenesis, fatty acid oxidation, fibrosis and inflammation. Finally, our in vitro mechanistic studies showed that while CD36 was involved in upregulation of proinflammatory molecules in macrophages by palmitic acid (PA) and lipopolysaccharide (LPS), GPR40 activation in macrophages exerts anti-inflammatory effects. Taken together, this study demonstrated for the first time that loss of GPR40 in LDLR-deficient mice exacerbated HFD-induced hyperlipidemia, hepatic steatosis, inflammation and fibrosis potentially through a CD36-dependent mechanism, suggesting that GPR40 may play a beneficial role in hyperlipidemia-associated NASH in LDLR-deficient mice.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperlipidemias , Síndrome Metabólica , Hepatopatia Gordurosa não Alcoólica , Animais , Humanos , Camundongos , Antígenos CD36/genética , Antígenos CD36/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica , Ácidos Graxos não Esterificados/metabolismo , Fibrose , Hiperlipidemias/complicações , Hiperlipidemias/genética , Inflamação/patologia , Fígado/metabolismo , Síndrome Metabólica/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Receptores de LDL/metabolismo
20.
Front Immunol ; 13: 1024755, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36341335

RESUMO

Background: CT053PTSA is a novel tyrosine kinase inhibitor that targets MET, AXL, VEGFR2, FLT3 and MERTK. Here, we present preclinical data about CT053PTSA, and we conducted the first-in-human (FIH) study to evaluate the use of CT053PTSA in adult patients with pretreated advanced solid tumors. Methods: The selectivity and antitumor activity of CT053PTSA were assessed in cell lines in vitro through kinase and cellular screening panels and in cell line-derived tumor xenograft (CDX) and patient-derived xenograft (PDX) models in vivo. The FIH, phase I, single-center, single-arm, dose escalation (3 + 3 design) study was conducted, patients received at least one dose of CT053PTSA (15 mg QD, 30 mg QD, 60 mg QD, 100 mg QD, and 150 mg QD). The primary objectives were to assess safety and tolerability, to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and the recommended dose of CT053PTSA for further study. Secondary objectives included pharmacokinetics, antitumor activity. Results: CT053 (free-base form of CT053PTSA) inhibited MET, AXL, VEGFR2, FLT3 and MERTK phosphorylation and suppressed tumor cell angiogenesis by blocking VEGF and HGF, respectively, in vitro. Moreover, cell lines with high MET expression exhibited strong sensitivity to CT053, and CT053 blocked the MET and AXL signaling pathways. In an in vivo study, CT053 significantly inhibited tumor growth in CDX and PDX models. Twenty eligible patients were enrolled in the FIH phase I trial. The most common treatment-related adverse events were transaminase elevation (65%), leukopenia (45%) and neutropenia (35%). DLTs occurred in 3 patients, 1/6 in the 100 mg group and 2/4 in the 150 mg group, so the MTD was set to 100 mg. CT053PTSA was rapidly absorbed after the oral administration of a single dose, and the Cmax and AUC increased proportionally as the dose increased. A total of 17 patients in this trial underwent tumor imaging evaluation, and 29.4% had stable disease. Conclusions: CT053PTSA has potent antitumor and antiangiogenic activity in preclinical models. In this FIH phase I trial, CT053PTSA was well tolerated and had a satisfactory safety profile. Further trials evaluating the clinical activity of CT053PTSA are ongoing.


Assuntos
Neoplasias , Inibidores de Proteínas Quinases , Adulto , Humanos , c-Mer Tirosina Quinase , Inibidores de Proteínas Quinases/uso terapêutico , Neoplasias/patologia , Dose Máxima Tolerável , Administração Oral
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