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1.
Sci Total Environ ; 802: 149855, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34455280

RESUMO

In order to realize the active and synchronous control of nitrogen (N) and organic matter (OM) release from sediments, this study compared the spatiotemporal changes in the physical, chemical, and biological indicators in the water system under different CaO2 dosing modes. Results from 90-day incubation experiment showed that CaO2 formed a dense barrier layer near its dosing position, improved the anoxic condition of water system, increased the physical adsorption of pollutants by sediments, and reduced the nutrients in overlying water, interstitial water, and sediments. Comprehensive comparison, the improvement effect of shallow injection group (I1) was the most obvious. Meanwhile, the activities of ammonia oxidizing bacteria and nitrite oxidizing bacteria near dosing position and those of denitrifiers and anammox bacteria adjacent to dosing site were significantly increased in all test groups (p < 0.01), thereby realizing the biological removal of N and OM in sediments. In addition, DO and ORP were steadily higher than 5 mg L-1 and 100 mV in I1, where the NH4+-N concentration in overlying water was stable below 1 mg L-1, and the easily released N content in the upper (0-3 cm) and middle (4-6 cm) sediments decreased by 41.64% and 43.56%, respectively. Compared with the large pollutant flux in control (14.31 TN mg m-2 d-1 and 194.05 mg TCOD m-2 d-1), I1 completely inhibited the pollutant release and reduced the original nutrients in overlying water. In general, CaO2 efficiently and synchronously controlled the endogenous release of N and OM under the combined actions of physical interception, physical adsorption, chemical oxidation, and biological transformation. Therefore, this study may provide valuable reference and guidance for the active and synchronous removal of N and OM in sediments and inhibition of endogenous pollutant release under anoxic condition.


Assuntos
Nitrogênio , Poluentes Químicos da Água , Sedimentos Geológicos , Nitrogênio/análise , Peróxidos , Fósforo , Poluentes Químicos da Água/análise
2.
Neural Regen Res ; 17(1): 170-177, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34100453

RESUMO

Ghrelin is a neuropeptide that has various physiological functions and has been demonstrated to be neuroprotective in a number of neurological disease models. However, the underlying mechanisms of ghrelin in Parkinson's disease remain largely unexplored. The current study aimed to study the effects of ghrelin in a 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease model and evaluate the potential underlying mechanisms. In the present study, we treated an SH-SY5Y cell model with 6-OHDA, and observed that pretreatment with different concentrations of ghrelin (1, 10, and 100 nM) for 30 minutes relieved the neurotoxic effects of 6-OHDA, as revealed by Cell Counting Kit-8 and Annexin V/propidium iodide (PI) apoptosis assays. Reverse transcription quantitative polymerase chain reaction and western blot assay results demonstrated that 6-OHDA treatment upregulated α-synuclein and lincRNA-p21 and downregulated TG-interacting factor 1 (TGIF1), which was predicted as a potential transcription regulator of the gene encoding α-synuclein (SNCA). Ghrelin pretreatment was able to reverse the trends caused by 6-OHDA. The Annexin V/PI apoptosis assay results revealed that inhibiting either α-synuclein or lincRNA-p21 expression with small interfering RNA (siRNA) relieved 6-OHDA-induced cell apoptosis. Furthermore, inhibiting lincRNA-p21 also partially upregulated TGIF1. By retrieving information from a bioinformatics database and performing both double luciferase and RNA immunoprecipitation assays, we found that lincRNA-p21 and TGIF1 were able to form a double-stranded RNA-binding protein Staufen homolog 1 (STAU1) binding site and further activate the STAU1-mediated mRNA decay pathway. In addition, TGIF1 was able to transcriptionally regulate α-synuclein expression by binding to the promoter of SNCA. The Annexin V/PI apoptosis assay results showed that either knockdown of TGIF1 or overexpression of lincRNA-p21 notably abolished the neuroprotective effects of ghrelin against 6-OHDA-induced neurotoxicity. Collectively, these findings suggest that ghrelin exerts neuroprotective effects against 6-OHDA-induced neurotoxicity via the lincRNA-p21/TGIF1/α-synuclein pathway.

3.
ACS Nano ; 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34851083

RESUMO

Current lung cancer diagnosis methods encounter delayed visual confirmation of tumor foci and low-resolution metrics in imaging findings, which delays the early treatment of tumors. Here, we developed a potent lung cancer imaging and treatment strategy centered around a nanotransformational concept of tumor iron mineralization in situ, which employs Prussian blue/calcium peroxide nanocomposites as a precursor. The resultant iron mineralization in tumor cells greatly facilitates the early and differential diagnosis of lung carcinoma from benign nodules via medical imaging, meanwhile introducing oxidative stress to activate the cellular apoptosis and ferroptosis pathways, resulting in inhibition of the malignant behavior of tumor cells. Tumor-microenvironment-triggered iron mineralization enables integration of the detection and prevention of tumor metastasis at its early stages with no assistance of toxic drugs, which offers a potential solution for the precise management of lung cancer with ideal outcomes.

5.
Infect Drug Resist ; 14: 4689-4697, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34785916

RESUMO

Background: The antimicrobial activities of some new oxazolidinones against slowly growing mycobacteria (SGM) have never been well evaluated. Methods: We evaluate the in vitro susceptibility of 20 reference strains and 157 clinical isolates, pertaining different SGM species, against four oxazolidinones, ie, delpazolid, sutezolid, tedizolid and linezolid. In addition, the association of linezolid resistance and mutations in 23srRNA, rplC, rplD were also tested. Results: Sutezolid presented the strongest antimicrobial activity against the clinical isolates of M. intracellulare than the other oxazolidinones, with MIC50 at 2 µg/mL and MIC90 at 4 µg/mL. MICs of sutezolid were usually 4- to 8-fold lower than these of linezolid against M. intracellulare and M. avium. The tested isolates of M. kansasii were susceptible to all of the four oxazolidinones. According to the multiple sequence alignment, novel 23srRNA mutations (A2267C and A2266G) in M. intracellulare and rplD mutations (Thr147Ala) in M. avium were identified in this study which have plausible involvement in rendering resistance against linezolid. Conclusion: This study showed that sutezolid harbors the strongest inhibitory activity against M. intracellulare, M. avium and M. kansasii in vitro, which provided important insights on the potential clinical application of oxazolidinones for treating SGM infections.

6.
Pathol Oncol Res ; 27: 1609941, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34776794

RESUMO

Objective: To develop and validate ubiquitination-related molecular subtypes and a novel prognostic index using ubiquitination-related genes (URGs) for patients with bladder cancer (BCa). Materials and Methods: We downloaded the clinical data and transcriptome data of BCa from TCGA and GEO database. Consensus clustering analysis was conducted to identify ubiquitination-related molecular subtypes for BCa. Besides, we performed univariate and multivariate Cox regression analysis to develop a novel prognostic URGs-related index for BCa. We conducted internal and external verification in TCGA cohort and GEO cohort, respectively. Furthermore, the associations of ubiquitination-related molecular subtypes and prognostic index with tumor immune environment were also investigated. Results: A total of four ubiquitination-related molecular subtypes of BCa were finally identified. These four molecular subtypes had significantly different clinical characteristics, prognosis, PD-L1 expression level and tumor microenvironment. Besides, we developed a novel prognostic index using six URGs (including HLA-A, TMEM129, UBE2D1, UBE2N, UBE2T and USP5). The difference in OS between high and low-risk group was statistically significant in training cohort, testing cohort, and validating cohort. The area under ROC curve (AUC) for OS prediction was 0.736, 0.723, and 0.683 in training cohort, testing cohort, and validating cohort, respectively. Multivariate survival analysis showed that this index was an independent predictor for OS. This prognostic index was especially suitable for subtype 1 and 3, older, male, high grade, AJCC stage III-IV, stage N0, stage T3-4 BCa patients. Conclusions: This study identified a total of four ubiquitination-related molecular subtypes with significantly different tumor microenvironment, prognosis, clinical characteristics and PD-L1 expression level. Besides, a novel ubiquitination-related prognostic index for BCa patients was developed and successfully verified, which performed well in predicting prognosis of BCa.

7.
J Nat Prod ; 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34846891

RESUMO

A new cytochalasin dimer, verruculoid A (1), three new cytochalasin derivatives, including 12-nor-cytochalasin F (2), 22-methoxycytochalasin B6 (3), and 19-hydroxycytochalasin B (4), and 20-deoxycytochalasin B (5), a synthetic product obtained as a natural product for the first time, together with four known analogues (6-9), were isolated and identified from the culture extract of Curvularia verruculosa CS-129, an endozoic fungus obtained from the inner fresh tissue of the deep-sea squat lobster Shinkaia crosnieri, which was collected from the cold seep area of the South China Sea. Structurally, verruculoid A (1) represents the first cytochalasin homodimer containing a thioether bridge, while 12-nor-cytochalasin F (2) is the first 12-nor-cytochalasin derivative. Their structures were elucidated by detailed interpretation of the NMR spectroscopic and mass spectrometric data. X-ray crystallographic analysis and ECD calculations confirmed their structures and absolute configurations. Compound 1 displayed activity against the human pathogenic bacterium Escherichia coli (MIC = 2 µg/mL), while compounds 4, 8, and 9 showed cytotoxicity against three tumor cell lines (HCT-116, HepG-2, and MCF-7) with IC50 values from 5.2 to 12 µM. The structure-activity relationship was briefly discussed.

8.
Environ Pollut ; 293: 118566, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34822944

RESUMO

The alkaline mineral amendment is a practical means of alleviating Cd concentration in rice grain (CdR) in the short-term; however, the long-term remediation effect of mineral amendment on the CdR and the eco-environmental controls remains unknown. Here a mineral (Si-Ca-Mg) amendment, calcined primarily from molybdenum tailings and dolomite, was applied biannually over 6 years (12 seasons) to acidic and moderately Cd-contaminated double-rice cropping ecosystems. This study investigated the inter-annual variation of Cd in the rice-soil ecosystem and the eco-environmental controls in subtropical rice ecosystems. CdR was reduced by 50%-86% following mineral amendment. The within-year reduction in CdR was similar between early rice (50%-86%, mean of 68%) and late rice (68%-85%, mean of 74%), leading to CdR in all early rice and in 83% of late rice samples below the upper limit (0.2 mg kg-1) of the China National Food Safety Standards. In contrast, the inter-annual reduction in CdR was moderately variable, showing a greater CdR reduction in the later 3 years (73%-86%) than in the former 3 years (54%-79%). Three years continuous mineral amendment was required to guarantee the safety rice production. The concentrations of DTPA-extractable and exchangeable Cd fractions in soil were reduced, while the concentration of oxides-bound Cd was increased. In addition, the soil pH, concentrations of Olsen-P and exchangeable Ca and Mg were elevated. These imply a lower apparent phytoavailability of Cd in the soil following mineral amendment. An empirical model of the 3-variable using soil DTPA-Cd, soil Olsen-P, and a climatic factor (precipitation) effectively predicted temporal changes in CdR. Our study demonstrates that Cd phytoavailability in soil (indexed by DTPA-extractable Cd) and climatic factors (e.g., temperature and precipitation) may directly/indirectly control the inter-annual reduction in CdR following mineral amendment in slightly and moderately Cd-contaminated paddy ecosystems.

9.
Clin Nutr ; 40(12): 5792-5801, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34775222

RESUMO

OBJECTIVE: To investigate the predictors of response to intravesical Bacillus Calmette-Guerin (BCG) immunotherapy for intermediate and high-risk non-muscle invasive bladder cancer (NMIBC) patients. MATERIALS AND METHODS: We retrospectively analyzed the clinicopathological data of 184 intermediate and high risk NMIBC cases receiving transurethral resection of bladder tumor (TURBT) and intravesical BCG immunotherapy from December 2014 to April 2021 at our center. All patients were divided into BCG responders and non-responders. Multivariate Logistic regression analysis was performed to identify the independent predictors of response to intravesical BCG immunotherapy. Univariate and multivariate Cox regression analyses were applied to explore the independent prognostic factors of recurrence-free survival (RFS). Receiver operating characteristic (ROC) curve and Kaplan-Meier survival analysis were also utilized. RESULTS: The RFS of BCG responders was significantly increased compared with BCG non-responders. Multivariate Cox regression analysis demonstrated that low grade, pTa stage, non-CIS, lower relative visceral fat area (rVFA) and lower systemic immune inflammation index (SII) were independent prognostic factors of increased RFS after intravesical BCG immunotherapy. Multivariate Logistic regression analysis demonstrated that pTa stage, low grade, non-CIS, low rVFA, and low SII were independent predictors of response to intravesical BCG immunotherapy. Kaplan-Meier survival analysis indicated that the RFS of patients in low rVFA group or low SII group was significantly increased in comparison with those in high rVFA group or high SII group. ROC curve analysis showed that the area under ROC (AUC) of including SII and rVFA was significantly increased, indicating that the inclusion of preoperative SII and rVFA could significantly improve the predictive efficiency. CONCLUSIONS: Low grade, pTa stage, non-CIS, preoperative lower rVFA and lower SII were vital independent predictors of response to intravesical BCG immunotherapy and were associated with preferable prognosis in NMIBC patients. The inclusion of preoperative SII and rVFA could significantly improve the predictive efficiency.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34826074

RESUMO

The spatio-temporal response of water quality in the receiving basins to water transfer remains unclear when considering more practical factors. Moreover, a much fast surrogate model is highly required to realize the purpose of rapid prediction of water quality. In this study, a two-dimensional hydrodynamic and water quality model was primarily established by considering the most comprehensive important pollution sources so far to investigate the water quality variation in Baiyangdian Lake, China. The pollution sources include atmospheric deposition, sediment release, village and tourism domestic sewage, livestock breeding, rainfall runoff, aquatic plants, and animals. The water quality at different sample sites was assessed using the water quality index (WQI). Subsequently, a surrogate model was proposed using the nonlinear autoregressive network with exogenous inputs (NARX), and the NARX model can realize fast prediction of the annual time series of water quality in a few seconds. The results showed that there are significant differences in water quality at different sample sites in each season. The highest WQI value occurred in autumn (65.46), and the average values at different sample sites were between 47.54 and 58.22 in this season. The water quality at Nanliuzhuang site and Caiputai site was significantly affected by water transfer patterns. In addition, the correlation coefficient R2 between the predicted results and the simulated ones except that of parameter TP was larger than 0.90. The prediction performance of surrogate model was shown to be very high efficiency and accurate. The proposed models and the results of this approach are guiding significance for lake management.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34824593

RESUMO

Trichosanthes kirilowii Maxim. and Bulbus allii Macrostemi are the components of Gualou Xiebai decoction (GLXB), a commonly used herbal combination for the treatment of coronary heart disease (CHD) in traditional Chinese medicine. Although GLXB is associated with a good clinical effect, its active compounds and mechanism of action remain unclear, which limits its clinical application and the development of novel drugs. In this study, we explored key compounds, targets, and mechanisms of action for GLXB in the treatment of CHD using the network pharmacology approach. We identified 18 compounds and 21 action targets via database screening. Enrichment analysis indicated that the effects of GLXB in patients with CHD are primarily associated with the regulation of signalling pathways for tumour necrosis factor, nuclear factor-kappa B, hypoxia-inducible factor-1, arachidonic acid metabolism, and insulin resistance. GLXB thus exerts anti-inflammatory, antihypoxic, and antiagglutinating effects; regulates lipid metabolism; and combats insulin resistance in CHD via these pathways, respectively. After reverse targeting, we observed that the main active compounds of GLXB in the treatment of CHD were quercetin, naringenin, ß-sitosterol, ethyl linolenate, ethyl linoleate, and prostaglandin B1. To explore the potential of these compounds in the treatment of CHD, we verified the affinity of the compounds and targets via molecular docking analysis. Our study provides a bridge for the transformation of natural herbs and molecular compounds into novel drug therapies for CHD.

12.
Comput Math Methods Med ; 2021: 3562942, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777562

RESUMO

Osteoporosis is a degenerative osteoarthropathy commonly found in old people and postmenopausal women. Many studies showed that microRNAs (miRNAs) can regulate the expression of osteoporosis-related genes and are abnormally expressed in patients with osteoporosis. miRNAs therefore have the potential to serve as biomarkers of osteoporosis. In this study, the limma package was used for the differential expression analysis of mRNA expression profiles and 357 significantly differentially expressed genes (DEGs) were obtained. Metascape was used for functional enrichment analysis of DEGs. The result revealed that DEGs were mainly enriched in signaling pathways like MAPK6/MAPK4. Based on the STRING database, the protein-protein interaction (PPI) network of DEGs was constructed. MCODE was used to analyze the functional subsets, and a key functional subset composed of 9 genes was screened out. In addition, the miRNA-mRNA regulatory interaction network (RegIN) was analyzed by the CyTargetLinker plugin, which generated 55 miRNA-mRNA regulatory interactions. Through literature searching, the osteoporosis-related gene FOXO1 in the key functional subset was determined to be the main object of the study. In qRT-PCR assay, the expression of the predicted miRNAs was tested in peripheral blood mononuclear cells of mice with osteoporosis, in which 13 miRNAs were remarkably highly expressed. All in all, this study, based on bioinformatics analysis and testing assay of miRNA expression, determined the potential biomarkers of osteoporosis.

13.
Int J Gen Med ; 14: 6325-6342, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34629897

RESUMO

Background: This study aimed to develop and validate a novel angiogenesis-related gene (ARG) signature and molecular subtypes by bioinformatics analysis. Materials and Methods: The transcriptome data and clinical data were obtained from TCGA and ICGC database. We performed consensus clustering analysis to identify angiogenesis molecular subtypes for ccRCC. Univariate and multivariate Cox regression analyses were used to develop a novel ARG-related signature as a prognostic biomarker for ccRCC. Internal and external validation were then performed in TCGA and ICGC cohort, respectively. Results: We identified a total of two angiogenesis molecular subtypes of ccRCC. The overall survival (OS) of subtype 1 ccRCC was significantly decreased compared with that of subtype 2 ccRCC (P=0.001). These two molecular subtypes have significantly different tumor microenvironment and immune checkpoint inhibitor sensitivities (P<0.05). Besides, we developed a novel signature based on three ARGs (including MSX1, TIMP1 and JAG2) for subtype 1 ccRCC. The difference in OS between high- and low-risk group was statistically significant in training cohort (P=0.009), test cohort (P=0.024), the whole type 1 cohort (P<0.001), and validation cohort (P=0.041). The AUC for one-year OS prediction was 0.732, 0.710, 0.725, and 0.645 in training cohort, test cohort, the whole type 1 cohort, and validation cohort, respectively. Independent prognostic analysis showed that this signature was an independent predictor for OS of subtype 1 ccRCC (P=0.028914). The power of this prognostic signature was superior to other signatures reported in previous studies. Conclusion: We developed and successfully validated a novel ARG signature for predicting prognosis of subtype 1 ccRCC, which was superior to several previous signatures.

14.
Front Oncol ; 11: 615881, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631509

RESUMO

Objective: To explore whether preoperative 18Fluorine-Fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) in combination with neutrophil-lymphocyte ratio (NLR) could accurately predict malignant lesions of upper urinary tract (UUT). Methods and Materials: The clinicopathologic data of a total of 252 patients with UUT lesions receiving surgical treatment at our center from January 2012 to November 2019 were retrospectively analyzed. All patients performed routine preoperative hematological examination, urine cytology, computed tomography urography (CTU), and 18F-FDG-PET/CT. Clinicopathologic data between 179 cases with malignancy (Group 1) and 73 cases with benign lesions (Group 2) were compared. Multivariate logistic regression analysis was used to explore the independent predictors of malignant UUT lesions. Receiver operating characteristic (ROC) curve was used to evaluate the predictive ability. Results: Among all patients, univariate analysis showed that NLR, hydronephrosis, CTU indicating malignancy, and PET/CT indicating malignancy were significantly associated with malignant UUT lesions; multivariate analysis revealed that NLR, CTU indicating malignancy, and PET/CT indicating malignancy were independent predictors of malignant UUT lesions; the area under ROC curve (AUC) of NLR, CTU, PET/CT, combining CTU and NLR, combining PET/CT and NLR, and combining PET/CT and CTU were 0.735, 0.788, 0.857, 0.863, 0.913, and 0.919, respectively, for postoperative pathological malignancy. Among 68 patients undergoing ureteroscopy biopsy, univariate analysis suggested that NLR, positive urine exfoliation cytology, CTU indicating malignancy, and PET/CT indicating malignancy were significantly associated with malignant UUT lesions; multivariate analysis demonstrated that positive urine cytology, PET/CT indicating malignancy, and NLR were independent predictors of malignant UUT lesions; the AUC of NLR, ureteroscopy biopsy, and combining PET/CT and NLR were 0.768, 0.853, and 0.839, respectively, for postoperative pathological malignancy. Conclusions: Combining preoperative NLR and PET/CT performed well in differentiating benign from malignant UUT lesions, which could not be identified by traditional imaging or urine cytology. Combining preoperative NLR and PET/CT could be used to reduce unnecessary ureteroscopy biopsy, which might result in tumor cell dissemination and risk of associated complications.

15.
Sci Total Environ ; : 151026, 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34666096

RESUMO

Organic fertilizers may contain cadmium (Cd) and the transformation of organic materials in soil also has a role in soil-plant Cd distribution, both of which lead to Cd accumulation in plant edible parts. However, the advisability of applying organic fertilizer to remediate soils that are moderately and slightly contaminated with Cd has not been clarified. In this study, we investigated the impacts of an organic amendment (chicken manure) on the Cd concentration in rice grains (CdR) and the soil chemical properties over a five year period (10 rice seasons) within a slightly contaminated paddy soil in Hunan Province, subtropical China. We found that the CdR was reduced by 28%-56% as a result of the organic amendment. The within-year reduction in CdR was higher in late rice (43%-56%, averaging 51%) than in early rice (28%-45%, averaging 38%); however, the inter-annual reduction in CdR was fairly stable (40%-49%), which suggests that chicken manure amendment has a long-term and persistent remediation potential. The concentrations of DTPA-extractable Cd and exchangeable plus water-soluble Cd fractions in soil were reduced, whereas soil pH and the concentrations of soil organic C and its labile fractions increased. These results indicate a lower apparent phytoavailability of Cd in soil following organic amendment. A two-variable empirical model using DTPA-Cd extracted from the soil at the full heading stage of rice and a climatic factor (total precipitation during the rice growing season) showed great potential in effectively predicting CdR. Our study suggests that Cd phytoavailability in soil (indexed by DTPA-extractable and exchangeable Cd) and climatic factors (such as temperature and precipitation) may control inter-annual reductions in CdR following organic amendment in slightly contaminated paddy soils.

16.
Singapore Med J ; 2021 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-34600448

RESUMO

INTRODUCTION: The growing years are paramount for bone growth and mineral accrual. Children with long-term neurological condition (LTNC) have multiple risk factors for poor bone health and fragility fractures. In Singapore, this has not been studied systematically therefore we aim to evaluate the risk factors associated with fragilty fractures in children with LTNC. METHODS: In this study, the search for fragility fractures was done by a retrospective review of patients with LTNC who are under follow-up in the Paediatric Neurology clinic and of patients who presented with fracture to the Paediatric Orthopaedic clinic. Information on patient's demographics, medical history, intervention, biochemical bone markers and fracture history were collected. RESULTS: In a tertiary clinic population of 136 patients with LTNC, 65% were dependent on mobility (GMFCS V), 60% were underweight and 60% were fed via gastrostomy or nasogastric tube, or on oral pureed diet. Furthermore, 60% were on anticonvulsants. The fracture rate was 3% in this population and was associated with low-impact activities such as transfer and dressing. Only 7.4% had a vitamin D level measured and 33% had calcium measured. CONCLUSION: The local prevalence of fragility fractures in children with LTNC who are under follow-up at the Neurology clinic was found to be 3%. Risk factors identified were limited ambulation and compromised nutritional status associated with feeding difficulty. Recommendations to optimize bone health in children with LTNC were made. These include promoting weight-bearing activities, looking out for underweight, avoiding vitamin D deficiency and ensuring adequate calcium intake.

17.
Cell Death Dis ; 12(11): 1035, 2021 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-34718335

RESUMO

In glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH), downregulated osteogenic ability and damaged blood supply are two key pathogenic mechanisms. Studies suggested that cannabinoid receptor 2 (CB2) is expressed in bone tissue and it plays a positive role in osteogenesis. However, whether CB2 could enhance bone formation and blood supply in GC-induced ONFH remains unknown. In this study, we focused on the effect of CB2 in GC-induced ONFH and possible mechanisms in vitro and in vivo. By using GC-induced ONFH rat model, rat-bone mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) to address the interaction of CB2 in vitro and in vivo, we evaluate the osteogenic and angiogenic effect variation and possible mechanisms. Micro-CT, histological staining, angiography, calcein labeling, Alizarin red staining (ARS), alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) staining, TUNEL staining, migration assay, scratch assay, and tube formation were applied in this study. Our results showed that selective activation of CB2 alleviates GC-induced ONFH. The activation of CB2 strengthened the osteogenic activity of BMSCs under the influence of GCs by promotion of GSK-3ß/ß-catenin signaling pathway. Furthermore, CB2 promoted HUVECs migration and tube-forming capacities. Our findings indicated that CB2 may serve as a rational new treatment strategy against GC-induced ONFH by osteogenesis activation and maintenance of blood supply.

18.
Chem Commun (Camb) ; 57(90): 11988-11991, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34709257

RESUMO

Synthesis of 1,4-enynes was performed via nickel-catalyzed cross-coupling of allylic alcohols with alkynylzinc reagents. The reaction features high regio- and E/Z-selectivity when aryl-substituted allylic alcohols were employed. The method also exhibits a wide scope of substrates and good compatibility of functional groups.

19.
Wound Repair Regen ; 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34665905

RESUMO

This study aimed to establish a novel gouty ulcer rat model induced by monosodium urate (MSU) deposition and preliminarily explored how MSU crystals affected wound healing. MSU crystals were subcutaneously injected into the back of rats to simulate tophi formation and ulceration. Ultrasound was used to detect the formation of gouty tophi. MSU crystal deposition and histopathological changes were analysed by haematoxylin-eosin staining. After the skin over the tophi became broken in the model group, a full-thickness tissue defect of the same area was made on the backs of the phosphate buffered saline (PBS) controls. On Days 3, 7, and 14 after wounding, the infiltration of neutrophils and macrophages and the expression of inflammatory markers, including interleukin-1ß (IL-1ß), tumour necrosis factor-α (TNF-α), and Nod-like receptor protein 3 (NLRP3), were examined by immunohistochemical staining and Western blotting, respectively. After the first subcutaneous injection in rats, local tissues showed redness and swelling, indicating inflammation on approximately Day 14. Tophi-like manifestations appeared on approximately Day 18. Tophi appeared heterogeneously hyperechoic by ultrasound. Swelling and redness in injured tissue areas increased on approximately Day 22, skin tissue necrosis was seen in a small area on approximately Day 26, and skin necrosis was enlarged and the tophi were ulcerated on approximately Day 32, accompanied by yellowish-white, chalky secretions. Haematoxylin and eosin staining showed dermal deposition of needle-like crystals with surrounding granulomatous inflammation. On Days 3, 7, and 14 after wounding, immunohistochemical staining showed the infiltration of neutrophils and macrophages, and the expression of inflammation-related proteins (IL-1ß, TNF-α, and NLRP3) were upregulated in gouty ulcers compared with those of PBS controls. The gouty ulcers were not completely healed by Day 14 compared with those in the PBS controls. In this study, a novel gouty ulcer rat model was constructed, which also revealed the existence of persistent chronic inflammation.

20.
Front Cardiovasc Med ; 8: 724713, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34660725

RESUMO

Background: CO2-derived parameters are increasingly used to identify either low-flow status or anaerobic metabolism in shock resuscitation. However, the performance of CO2-derived parameters in cardiac surgical patients is poorly understood. This study aims to compare the performance of lactate and CO2-derived parameters in predicting major postoperative complications after cardiac surgery with cardiopulmonary bypass. Methods: This is a prospective, single-center, diagnostic accuracy study. All patients who receive elective cardiac surgery involving cardiopulmonary bypass will be screened for study eligibility. Blood samples will be taken for the calculation of CO2-derived parameters, including the venous-arterial difference in CO2 partial pressure (PCO2 gap), venous-arterial difference in CO2 content to arterial-venous O2 content ratio (Cv-aCO2/Ca-vO2), and venous-arterial difference in CO2 partial pressure to arterial-venous O2 content ratio (Pv-aCO2/Ca-vO2) at ICU admission, and 3, 6, and 12 h later. Baseline, perioperative data will be collected daily for 7 days; patients will be followed up for 28 days to collect outcome data. The primary endpoint is the occurrence of major postoperative complications. Receiver-operating characteristics (ROC) curve analysis will be carried out to assess the predictive performance of lactate and CO2-derived parameters. The performance of the ROC curves will be compared. Discussion: The performance of lactate and CO2-derived parameters in predicting major postoperative complications will be investigated in the non-sepsis population, which has not been extensively investigated. Our study will compare the two surrogates of respiratory quotient directly, which is an important strength. Trial Registration: ChiCTR, ChiCTR2000029365. Registered January 26th, 2020, http://www.chictr.org.cn/showproj.aspx?proj=48744.

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