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1.
Thromb Res ; 210: 70-77, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-35026611

RESUMO

INTRODUCTION: Purpura fulminans (PF) is a hematological emergency that can be caused by severe congenital protein C (PC) deficiency. It has been rarely reported in the Chinese population. We aimed to characterize the clinical and genetic features of Chinese pediatric patients with severe congenital PC deficiency who first presented with PF. MATERIALS AND METHODS: Twelve pediatric patients were diagnosed with severe congenital PC deficiency with PF, which was diagnosed based on our hospital records and previous reports from 1988 to July 2021 in China. We evaluated the clinical and genetic features of these patients. RESULTS: Nine patients (9/12, 75%) had onsets that were observed within the first 48 h after birth. Six patients had a family history of thromboembolism. There was no consanguinity. Other symptoms were intracranial thrombosis or hemorrhage (4, 33.3%), ocular lesions (2, 16.7%), gastrointestinal hemorrhage (2, 16.7%) and kidney infarction before birth (1, 8.3%). All but one of the patients (one case not detected) had a plasma PC activity of <10%. The genetic study indicated that in the eight patients with inherited PC deficiency, two were homozygous, five were compound heterozygous and one was heterozygous for PC deficiency. CONCLUSION: This is the first and largest case series of Chinese pediatric patients with severe congenital PC deficiency who first presented with PF. It has been shown that treatment with both fresh frozen plasma and anticoagulants is recommended when PC concentrate is not easily available, especially in developing countries.

2.
Food Res Int ; 151: 110841, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34980380

RESUMO

Inflammatory bowel disease afflicted individuals and most medications have adverse effects. The objection of this study is to investigate whether the major yolk protein (MYP) could aid in the remission of colitis. The function of MYP on acute colitis was assessed through a dextran sulfate sodium -induced colitis mice model. Compared to the model group, the anti-inflammatory cytokines increased significantly in the MYP group, whereas the pro-inflammatory cytokines were not significantly different between the model and treatment group. The results also showed that supplementation of MYP improved the shift in microbial community composition of mice with colitis induced by DSS. In addition, MYP supplementation enriched the contents of fecal short-chain fatty acids. The alleviation of MYP on the colitis was probably related to repair the dysbiosis state of colonic microbiota, which thus induced an increase in short-chain fatty acids level and secrete anti-inflammatory cytokines (IL-4 and IL-10). In sum, oral MYP may be a potential candidate for the attenuating of acute colitis.

3.
Sci Total Environ ; 806(Pt 3): 151214, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34715225

RESUMO

Soil contamination with multiple heavy metals has always been a pressing issue, but little attention has been given to V and Cr and their chemical fractions' impacts on microorganisms because Cr2O3 usually occurs as an associated mineral in vanadium mines. To investigate this issue, samples (N1-N6) less affected by anthropogenic activities were selected for microbial analysis. The area near the refinery was heavily contaminated according to the PLI (pollution load index). Actinobacteriota, Proteobacteria, and Chloroflexi were the dominant phyla in the soil. The diversity of bacteria was positively influenced by V and Cr and negatively influenced by pH, while the abundance was positively correlated with soil nutrients. Interestingly, the influence of heavy metals in the residual fraction on the microbial community structure and functional metabolism was higher than that in the oxidizable fraction, which may be due to the relatively low heavy metal valence of the oxidizable fraction, suggesting that low valence binding forms of multivalence elements have little effect on microorganisms in the soil. Ultimately, two strains with great efficiency in reducing V and Cr were screened, and co-occurrence network characteristics with significant positive interactions suggested that Bacillus can coordinate community structure in the same niche. This research will help to explore the bioavailability of heavy metals and further achieve the bioremediation of heavy metal contamination in soil.


Assuntos
Poluentes do Solo , Vanádio , Bactérias , Biodegradação Ambiental , Óxido Ferroso-Férrico , Microbiologia do Solo , Poluentes do Solo/análise , Titânio
4.
Artigo em Inglês | MEDLINE | ID: mdl-34925531

RESUMO

Slow transit constipation (STC) is a common type of constipation with a high incidence rate and a large number of patients. We aimed to investigate the therapeutic effects and potential mechanism of paeoniflorin (PAE) on loperamide-induced Sprague Dawley (SD) rat constipation models. Rats with loperamide-induced constipation were orally administered different concentrations of PAE (10, 20, or 40 mg/kg). In vitro, enterochromaffin (EC)-like RIN-14B cells were treated with 20, 40, or 80 µg/ml PAE. We found that PAE treatment significantly improved the symptoms of constipation and increased the intestinal transit rate. Hematoxylin and eosin (H&E) staining showed that PAE alleviated colonic tissue pathological damage. Besides, our results implied that PAE concentration-dependently promoted the content of 5-hydroxytryptamine (5-HT) catalyzed by tryptophan hydroxylase (Tph)-1 in the serum of loperamide-induced rats and in RIN-14B cells. Western blot and immunofluorescence (IF) stain indicated that PAE also promoted the expression of G protein-coupled BA receptor 1 (TGR5), transient receptor potential ankyrin 1 (TRPA1), phospholipase C (PLC)-γ1, and phosphatidylinositol 4,5-bisphosphate (PIP2) in vivo and in vitro. RIN-14B cells were cotreated with a TGR5 inhibitor (SBI-115) to explore the mechanism of PAE in regulating the 5-HT secretion. We observed inhibition of TGR5 reversed the increase of 5-HT secretion induced by PAE in RIN-14B cells. We provided evidence that PAE could promote 5-HT release from EC cells and improve constipation by activating the TRPA1 channel and PLC-γ1/PIP2 signaling. Thus, PAE may provide therapeutic effects for patients with STC.

5.
Front Oncol ; 11: 755188, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34938655

RESUMO

Background: Despite much improvement in the treatment for acute lymphoblastic leukemia (ALL), childhood ALLs with MLL-rearrangement (MLL-r) still have inferior dismal prognosis. Thus, defining mechanisms underlying MLL-r ALL maintenance is critical for developing effective therapy. Methods: GSE13159 and GSE28497 were selected via the Oncomine website. Differentially expressed genes (DEGs) between MLL-r ALLs and normal samples were identified by R software. Next, functional enrichment analysis of these DEGs were carried out by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). Then, the key hub genes and modules were identified by Weighted Gene Co-expression Network Analysis (WGCNA). Therapeutically Applicable Research to Generate Effective Treatments (TARGET) ALL (Phase I) of UCSC Xena analysis, qPCR, and Kaplan-Meier analysis were conducted for validating the expression of key hub genes from bone marrow cells of childhood ALL patients or ALL cell lines. Results: A total of 1,045 DEGs were identified from GSE13159 and GSE28497. Through GO, KEGG, GSEA, and STRING analysis, we demonstrated that MLL-r ALLs were upregulating "nucleosome assembly" and "B cell receptor signal pathway" genes or proteins. WGCNA analysis found 18 gene modules using hierarchical clustering between MLL-r ALLs and normal. The Venn diagram was used to filter the 98 hub genes found in the key module with the 1,045 DEGs. We identified 18 hub genes from this process, 9 of which were found to be correlated with MLL-r status, using the UCSC Xena analysis. By using qPCR, we validated these 9 hub key genes to be upregulated in the MLL-r ALLs (RS4;11 and SEM) compared to the non-MLL-r ALL (RCH-ACV) cell lines. Three of these genes, BCL11A, GLT8D1 and NCBP2, were shown to be increased in MLL-r ALL patient bone marrows compared to the non-MLL-r ALL patient. Finally, Kaplan-Meier analysis indicated that childhood ALL patients with high BCL11A expression had significantly poor overall survival. Conclusion: These findings suggest that upregulated BCL11A gene expression in childhood ALLs may lead to MLL-r ALL development and BCL11A represents a new potential therapeutic target for childhood MLL-r ALL.

6.
Biomed Environ Sci ; 34(11): 847-858, 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34955145

RESUMO

Objective: This study aimed to understand the characteristics of dietary patterns among children aged 12 to 23 months and discusses the relationship between dietary patterns and the growth of children. Method: Cross-sectional data were selected from the National Nutrition and Health Systematic Survey for 0 to 18 year-old children in China ( n = 2,449) to describe the patterns of complementary feeding and the growth of children. Cluster analysis was used to analyze complementary feeding patterns, and an analysis of variance and Bonferroni test were conducted to analyze the relationship between Z scores and complementary feeding patterns. Results: Four dietary patterns were identified among the children via cluster analysis. In Pattern 4 ( n = 104, 4.2%), children still consumed milk as their staple food. They displayed the lowest grain, fruit, vegetable, egg, and flesh foods consumption, a medium frequency of breast milk consumption, and a high frequency of dairy product consumption. Pattern 4 had the lowest length-for-age Z scores and weight-for-age Z scores, with -0.10 ± 1.34 and 0.24 ± 1.00, respectively ( F = 7.940, P < 0.001; F = 5.317, P < 0.001). Conclusion: Although China is undergoing rapid urbanization and economic development, there is still a phenomenon of insufficient intake of protein-rich foods and dairy-based dietary patterns at the stage of complementary food introduced among children aged 12 to 23 months.


Assuntos
Crescimento , Fenômenos Fisiológicos da Nutrição do Lactente , China , Estudos Transversais , Feminino , Humanos , Lactente , Masculino
7.
Biomed Environ Sci ; 34(11): 891-899, 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34955149

RESUMO

The main purpose of the National Nutrition and Health Systematic Survey for children 0-17 years of age in China (CNHSC) was to collect basic data on the nutrition, development, and health status for children in different regions across China using evidence-based, reliable, and cost-effective approaches. Children and their parents or guardians from seven regions (south, southwest, north, northwest, eastern, central, and northeast China) in China were recruited. A multi-stage stratified randomized sampling method was used. Two provinces were randomly sampled from each of the seven regions, from which one urban district and one rural country were also randomly sampled, resulting in a total of 28 survey counties/districts. Dietary surveys, health examinations, laboratory testing, and questionnaires were used to collect dietary intake, nutritional status, child development, and health status information. Nutrition, health, and lifestyle assessment of children and their parents was determined using the Knowledge Attitude Practice (KAP) survey. Greater than 100,000 children (38,000 children < 6 years of age and 66,000 children 6-17 years of age) completed the survey. The survey provided comprehensive data on child nutrition and health status for future studies and will serve as the basis for an integrated nutrition and health improvement strategies proposal for children in China.


Assuntos
Desenvolvimento Infantil , Nível de Saúde , Inquéritos Epidemiológicos , Inquéritos Nutricionais , Adolescente , Criança , Pré-Escolar , China , Humanos , Lactente , Recém-Nascido
8.
Zhonghua Nan Ke Xue ; 27(1): 3-10, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-34914274

RESUMO

Objective: To establish a model of oxidative stress (OS) injury in mouse Leydig cells using α-α'-azodiisobutyramidine hydrochloride (AAPH) and evaluate the physiological function. METHODS: In Experiment 1, we treated mouse TM3 Leydig cells with AAPH at 0, 1, 5, 10, 50 and 100 mmol/L for 4, 8 and 24 h respectively and measured the activity of the cells using MTS, their aging by ß-galactoside staining, mitochondrial membrane potential by JC-1 fluorescence and mitochondrial DNA copy number by qPCR. In Experiment 2, we treated the TM3 cells selected in Experiment 1 according to the AAPH concentration range (≤10 mmol/L) with AAPH at 0, 0.1, 0.5, 1, 2, 4, 6, 8 and 10 mmol/L for 24, 48 and 72 h respectively, detected the activity and aging of the cells and the ROS positive rate, and determined the optimal concentration and time of AAPH in inducing OS injury in the TM3 cells. RESULTS: Experiment 1 showed that the survival rate of the TM3 cells was ≥50% in the 4-h 50 mmol/L, 8-h 10 mmol/L and 24-h 5 mmol/L AAPH groups, the initial concentration of AAPH was ≤10 mmol/L, with the action time of ≥24 h. Experiment 2 manifested that in the 24-h 6 mmol/L AAPH group, the survival rate of the TM3 cells was ≥70%, with an ROS positive rate of 56.88%, normal mitochondrial membrane potential, increased number of mtDNA copies, but no senescence. CONCLUSIONS: Treatment with AAPH at the concentration of 6 mmol/L for 24 hours is suitable for induction of OS injury in the TM3 cells.


Assuntos
Células Intersticiais do Testículo , Mitocôndrias , Animais , Masculino , Camundongos , Estresse Oxidativo
9.
Org Lett ; 23(22): 8937-8941, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34752114

RESUMO

An efficient formal (3 + 1 + 1) carboannulation strategy of Morita-Baylis-Hillman (MBH) carbonates with pyridinium ylides was developed for constructing diversely functionalized spiro-cyclopentadiene oxindoles. The reaction initiates with an SN2' olefination of MBH carbonates with pyridinium ylides. The in situ generated dienes then engage in a challenging (4 + 1) ylide carboannulation, which has been rarely reported before. The reaction features broad substrate scope as well as high chemo- and regioselectivity. (3 + 1 + 1) carboannulation products could be easily transformed into interesting spiro-cyclopenta[c]furan oxindoles.

10.
Mol Nutr Food Res ; : e2100724, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34780105

RESUMO

SCOPE: Dityrosine (DT), a marker of protein oxidation, is widely found in many high-protein foods. Dietary intake of DT induces myocardial oxidative stress injury and impairs energy metabolism. Lycopene is a common dietary supplement with antioxidant and mitochondrial-lipid homeostasis modulating abilities. This study aimed to examine the effects of lycopene on DT-induced disturbances in myocardial function and energy metabolism. METHODS AND RESULTS: Four-week-old C57BL/6J mice received intragastric administration of either tyrosine (420 µg kg-1 BW), DT (420 µg kg-1 BW), or lycopene at high (10 mg kg-1 BW) and low (5 mg kg-1 BW) doses for 35 days. Lycopene administration effectively reduced oxidative stress, cardiac fatty acid accumulation, and cardiac hypertrophy and improved mitochondrial performance in DT-induced mice. In vitro experiments in H9c2 cells showed that DT directly inhibited the activity of the respiratory chain complex, whereas oxidative phosphorylation and ß-oxidation gene expression is upregulated. Lycopene enhanced the activity of the complexes and inhibited ROS production caused by compensatory regulation. CONCLUSION: Lycopene improves DT-mediated myocardial energy homeostasis disorder by promoting the activity of respiratory chain complexes I and IV and alleviates the accumulation of cardiac fatty acids and myocardial hypertrophy.

11.
Appl Opt ; 60(31): 9933-9942, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34807183

RESUMO

Blind modulation format identification (MFI) is indispensable for correct signal demodulation and optical performance monitoring in future elastic optical networks (EON). Existing MFI schemes based on a clustering algorithm in Stokes space have gained good performance, while only limited types of modulation formats could be correctly identified, and the complexities are relatively high. In this work, we have proposed an MFI scheme with a low computational complexity, which combines an improved particle swarm optimization (I-PSO) clustering algorithm with a 2D Stokes plane. The main idea of I-PSO is to add a new field of view on each particle and limit each particle to only communicate with its neighbor particles, so as to realize the correct judgment of the number of multiple clusters (local extrema) on the density images of the s2-s3 plane. The effectiveness has been verified by 28 GBaud polarization division multiplexing (PDM)-BPSK/PDM-QPSK/PDM-8QAM/PDM-16QAM/PDM-32QAM/PDM-64QAM simulation EON systems and 28 GBaud PDM-QPSK/PDM-8QAM/PDM-16QAM/PDM-32QAM proof-of-concept transmission experiments. The results show that, using this MFI scheme, the minimum optical signal-to-noise ratio (OSNR) values to achieve 100% MFI success rate are all equal to or lower than those of the corresponding 7% forward error correction (FEC) thresholds. At the same time, the MFI scheme also obtains good tolerance to residual chromatic dispersion and differential group delay. Besides that, the proposed scheme achieves 100% MFI success rate within a maximum launch power range of -2∼+6 dBm. More importantly, its computational complexity can be denoted as O(N).

12.
Mol Nutr Food Res ; : e2100602, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34786857

RESUMO

SCOPE: Recent studies have linked high consumption of red and processed meats to an increased risk of non-alcoholic fatty liver disease, and cooking-induced oxidation of proteins and amino acids might be contributing factors. Herein, this study investigates the influence of oxidized pork and the protein oxidation biomarker dityrosine (Dityr) on hepatic steatosis in mice. METHODS AND RESULTS: Low- and high-oxidative injury pork (LOP and HOP) are freeze-dried to prepare mouse diets. Mice are fed a diet of either the control, LOP, HOP, LOP+Dityr, or Dityr for 12 weeks. HOP and Dityr intake induced oxidative stress and inflammation that impaired thyroid function and peripheral metabolism (reduced type 1 deiodinase activity) of thyroid hormones (THs). These lead to a decrease in the circulating as well as liver THs and induced hepatic steatosis. This process might be regulated through reduced TH levels and altered TH target genes and proteins related to hepatic lipid metabolism that ultimately inhibited hepatic energy metabolism, as indicated by increased hepatic lipid synthesis, decreased hepatic lipid catabolism, and fatty acid oxidation. CONCLUSION: HOP intake could induce hepatic steatosis by impairing TH function. Dityr plays an important role in the HOP-induced harmful effects.

13.
Nanoscale Res Lett ; 16(1): 154, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34637014

RESUMO

At bio-safe concentrations, black phosphorus nanoparticles activated TG2, and promote the expression of ECM, which further promoted osteogenic differentiation of EMSCs. From these results, we can conclude that black phosphorus nanoparticles are suitable as biological factors in bone tissue engineering. Black phosphorus nanoparticles (BPs) present excellent biocompatibility and good biodegradability, which have been rigorously studied and proven. However, its utilization in bone tissue engineering fields is still in its infancy. Thus, the main purpose of the present study was to investigate the effects of BPs on osteogenic differentiation of ectodermal mesenchymal stem cell (EMSC) in vitro. Biocompatible BPs with high yield were prepared with a simple and efficient ultrasonication technique. EMSCs were isolated from adult rat nasal respiratory mucosa. Then, we treated EMSCs with BPs at different concentrations in vitro and examined the effect of BPs on osteogenic differentiation of EMSCs. In addition, inhibitor of transglutaminase 2 (TG2) and western blot were used to clarify the mechanism of the promoting effect of BPs on osteogenesis. Our results indicated that BPs could significantly enhance osteogenic differentiation of EMSCs in vitro. Nevertheless, BPs had no effect on EMSCs proliferation. Mechanistically, BPs promoted osteogenesis differentiation of EMSCs through upregulating TG2 expression. These results highlight the advantage of using chemical materials for novel engineering strategies of these highly promising small molecules for bone-tissue regeneration.

14.
Oncol Lett ; 22(6): 812, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34671426

RESUMO

Colorectal cancer (CRC) is one of the most common types of malignancy worldwide and has a poor prognosis. Non-SMC condensing I complex subunit G (NCAPG) has been reported to be upregulated in numerous types of malignant tumor. However, to the best of our knowledge, its clinicopathological and biological significance in CRC remain to be elucidated. The results of the present study revealed that NCAPG expression levels were upregulated in human CRC tissues and cell lines. The upregulated expression of NCAPG was positively associated with patient clinicopathological characteristics, such as differentiation and tumor size, and independently associated with poor survival. Consistent with the clinical observations, NCAPG was discovered to promote the proliferation and inhibit the apoptosis of CRC cells. Moreover, NCAPG-knockdown inhibited CRC cell proliferation by regulating the PI3K/AKT signaling pathway. Furthermore, NCAPG was identified as a potential target of microRNA (miR)-23b-3p, which was subsequently demonstrated to negatively regulate NCAPG expression. In conclusion, the findings of the current study indicated that the miR-23b-3p/NCAPG/PI3K/AKT signaling axis may play an important role in CRC carcinogenesis, and the status of the molecule may represent a promising prognostic marker for the disease.

15.
J Cancer ; 12(21): 6320-6329, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659522

RESUMO

The family with sequence similarity 83, member A (FAM83A) gene is associated with the occurrence and development of many malignant tumors. Our aim was to explore the role of FAM83A in cervical cancer. FAM83A was overexpressed or knocked down in cervical cancer cells, and the expressions of FAM83A, key proteins involved in the epithelial-mesenchymal transition (EMT), and Wnt signaling pathway-related proteins were detected by western blot analysis. Cell proliferative and invasive abilities were also examined using cell proliferation, colony formation, and Matrigel invasion assays. Cells were treated with the Wnt pathway inhibitor XAV-939 to determine whether Wnt signaling was necessary for the effect of FAM83A on cervical cancer cells. FAM83A was highly expressed in cervical cancer tissues and was associated with differentiation, TNM stage, lymph node metastasis, and poor prognosis in patients with cervical cancer. Knockdown of FAM83A inhibited the proliferation, colony formation, and invasion of cervical cancer cells. The opposite results were observed in FAM83A-overexpressing cells, and FAM83A overexpression also promoted EMT and Wnt signaling. XAV-939 reversed the activation of Wnt signaling and EMT induced by FAM83A. In conclusion, FAM83A expression was increased in cervical cancers and correlated with poor prognosis of patients. FAM83A overexpression can activate the Wnt signaling pathway, facilitate EMT, and promote the proliferative and invasive abilities of cervical cancer cells.

16.
Antimicrob Agents Chemother ; : AAC0166821, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34662186

RESUMO

OBJECTIVE: We aimed to estimate the risk of varied antifungal therapy with azoles causing the syndrome of acquired apparent mineralocorticoid excess (AME) in the real-world practice. METHODS: First, we conducted a disproportionality analysis based on data from the FDA Adverse Event Reporting System (FAERS) database to characterize the signal differences of triazoles - related AME. Second, a systematic review was conducted, and to describe clinical features of AME cases reported in clinical practice. RESULTS: In the FAERS database, we identified 27 cases of triazoles - AME, posaconazole [ROR=865.37; 95%CI (464.14; 1613.45)] and itraconazole [ROR=556.21; 95% (303.05; 1020.85)] significantly increased the risk of AME events, while fluconazole, voriconazole and isavuconazole did not affect any of the mineralocorticoid excess targets. 18 studies with 39 cases raised evidence of AME following posaconazole and itraconazole treatment, and another 27 cases were identified by analysis of the description of clinical features in FAERS database. The average age of 66 patients was 55.5 years (6∼87 years). AME mainly occurs in patients with posaconazole concentrations above 3 µg/mL (mean=4.4µg/mL, range 1.8∼9.5µg/mL), and is less likely to occur when levels are below 2 µg/mL (6%). The median time to event onset was 11.5 weeks, and 50% of the adverse events occurred within 3 months for posaconazole. CONCLUSION: The presented study supports very recent findings that posaconazole and itraconazole but not the other three azole antifungals investigated are associated with AME and the effects were dose-dependent, which allows for a dose de-escalation strategy and for substitution with fluconazole, isavuconazole or voriconazole to resolve the adverse effects.

17.
BMC Fam Pract ; 22(1): 203, 2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34649515

RESUMO

BACKGROUND: Rural residents with chronic conditions have a stronger need for health services, which should make using family doctor contract services a priority. This study aimed to evaluate the rate of willingness among rural residents with chronic conditions to contract with family doctors and examine its determinants. METHODS: A cross-sectional study was conducted from May, 2018 to June, 2018 in Shandong Province in China. A total of 769 rural unsigned residents with chronic conditions were included in the analysis. Using the Andersen model as the theoretical framework, logistic regression models were chosen to analyse the factors associated with willingness to contract with family doctors. RESULTS: This study found that the rate of willingness to contract with family doctors among chronic patients in rural Shandong was 46.7%. A higher willingness was observed in those living a further distance from the village clinic (more than 600 m: OR = 1.85, 95%CI =1.17-2.93), having received publicity for family doctor contract services (OR = 1.71, 95% CI = 1.06-2.76), reporting need for utilizing a chronic disease management program (OR = 3.36, 95% CI = 2.20-5.23), and reporting need for higher medical insurance reimbursement (OR = 1.91, 95% CI = 1.28-2.83). CONCLUSIONS: The prevalence of contract willingness was relatively low among unsigned rural residents with chronic conditions in rural Shandong, China. The need factors were powerful factors affecting their willingness to contract with family doctors. The government should therefore strengthen targeted publicity and education to rural residents with chronic conditions and provide targeted healthcare services, such as chronic disease management programs and medical services with higher reimbursement rates, to promote their willingness to contract with family doctors.


Assuntos
Médicos de Família , População Rural , China , Doença Crônica , Estudos Transversais , Humanos
18.
Hum Mol Genet ; 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34590683

RESUMO

BACKGROUND: Activated neutrophil-derived exosomes reportedly contribute to the proliferation of airway smooth muscle cells (ASMCs), thereby aggravating the airway wall remodeling during asthma; however, the specific mechanism remains unclear. METHODS: Lipopolysaccharide (LPS)-EXO and si-CRNDE-EXO were extracted from the media of human neutrophils treated with LPS and LPS + si-CRNDE (a siRNA targets long non-coding RNA CRNDE), respectively. Human ASMCs were co-cultured with LPS-EXO or si-CRNDE-EXO, and cell viability, proliferation, and migration were measured. The interplay of CRNDE, inhibitor of nuclear factor kappa B kinase subunit beta (IKKß), and nuclear receptor subfamily 2 group C member 2 (TAK1) was explored using RNA immunoprecipitation (RIP) and Co-IP assays. A mouse model of asthma was induced using ovalbumin. RESULTS: CRNDE was upregulated in LPS-EXO and successfully transferred from LPS-treated neutrophils to ASMCs through exosome. Mechanically, CRNDE loaded in LPS-EXO reinforced TAK1-mediated IKKß phosphorylation, thereby activating the nuclear factor kappa B (NF-κB) pathway. Functionally, silencing CRNDE in LPS-EXO, an IKKß inhibitor, and an NF-κB inhibitor all removed the upregulation of cell viability, proliferation, and migration induced by LPS-EXO in ASMCs. In the end, the in vivo experiment demonstrated that CRNDE knockdown in neutrophils effectively reduced the thickness of bronchial smooth muscle in a mouse model for asthma. CONCLUSION: Activated neutrophils-derived CRNDE was transferred to ASMCs through exosomes and activated the NF-κB pathway by enhancing IKKß phosphorylation. The latter promoted the proliferation and migration of ASMCs and then contributed to airway remodeling in asthma.

19.
Acta Pharmacol Sin ; 42(11): 1913-1920, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34561552

RESUMO

Sepsis is a dysregulated immune response to infection and potentially leads to life-threatening organ dysfunction, which is often seen in serious Covid-19 patients. Disulfiram (DSF), an old drug that has been used to treat alcohol addiction for decades, has recently been identified as a potent inhibitor of the gasdermin D (GSDMD)-induced pore formation that causes pyroptosis and inflammatory cytokine release. Therefore, DSF represents a promising therapeutic for the treatment of inflammatory disorders. Lactoferrin (LF) is a multifunctional glycoprotein with potent antibacterial and anti-inflammatory activities that acts by neutralizing circulating endotoxins and activating cellular responses. In addition, LF has been well exploited as a drug nanocarrier and targeting ligands. In this study, we developed a DSF-LF nanoparticulate system (DSF-LF NP) for combining the immunosuppressive activities of both DSF and LF. DSF-LF NPs could effectively block pyroptosis and inflammatory cytokine release from macrophages. Treatment with DSF-LF NPs showed remarkable therapeutic effects on lipopolysaccharide (LPS)-induced sepsis. In addition, this therapeutic strategy was also applied to treat ulcerative colitis (UC), and substantial treatment efficacy was achieved in a murine colitis model. The underlying mode of action of these DSF-LF-NPs may contribute to efficiently suppressing macrophage-mediated inflammatory responses and ameliorating the complications caused by sepsis and UC. As macrophage pyroptosis plays a pivotal role in inflammation, this safe and effective biomimetic nanomedicine may offer a versatile therapeutic strategy for treating various inflammatory diseases by repurposing DSF.


Assuntos
COVID-19 , Colite Ulcerativa , Dissulfiram/farmacocinética , Lactoferrina , Síndrome de Resposta Inflamatória Sistêmica , Inibidores de Acetaldeído Desidrogenases/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Materiais Biomiméticos/farmacologia , COVID-19/tratamento farmacológico , COVID-19/imunologia , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/imunologia , Modelos Animais de Doenças , Dissulfiram/farmacologia , Portadores de Fármacos/farmacologia , Humanos , Imunossupressores/farmacologia , Lactoferrina/metabolismo , Lactoferrina/farmacologia , Lipopolissacarídeos/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas/uso terapêutico , Piroptose/efeitos dos fármacos , SARS-CoV-2 , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Síndrome de Resposta Inflamatória Sistêmica/metabolismo , Resultado do Tratamento
20.
Nurs Crit Care ; 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34382281

RESUMO

BACKGROUND: The current practice involves blood sampling from the circuit line to measure acid-base and electrolyte parameters during continuous renal replacement therapy (CRRT). However, there is limited evidence supporting its reliability due to the effects of anticoagulant mechanism and access recirculation associated with regional citrate anticoagulation (RCA). AIM: To evaluate the reliability of monitoring acid-base and electrolyte parameters through circuit lines in regular and reversed connections during RCA-CRRT. STUDY DESIGN: In this prospective cohort study, we included critically ill patients receiving RCA-CRRT via a double-lumen catheter. During the second hour after CRRT initiation, we collected blood samples to monitor acid-base and electrolyte parameters and their levels were compared between samples from the circuit lines (at 0, 3, and 5 minutes) and those from the central venous catheter (CVC) line (at 0 minute). During this time, CRRT switched to the replacement state as controls. RESULTS: We observed 128 CRRT circuits in 60 adult patients receiving RCA-CRRT. Ninety-eight (76.6%) circuits had regular connections, while 30 (23.4%) had reversed connections. Among regular connections, no differences were observed in any acid-base or electrolyte parameters between samples from the CVC line and those from the circuit line at all time points (P > .05). Among reversed connections, ionized calcium levels were dramatically decreased at all three time points in samples from the circuit line compared with those from the CVC line (0.65 ± 0.12, 0.72 ± 0.11, and 0.78 ± 0.99 vs 0.98 ± 0.07 mmol/L, P < .001), with comparable levels of other acid-base or electrolyte parameters between the sampling patterns (P > .05). CONCLUSIONS: Acid-base and electrolyte parameters could be reliably monitored through the circuit line during RCA-CRRT in regular connections. However, in reversed connections, pre-filter ionized calcium concentrations determined through the circuit line were lower than those determined through the CVC line. RELEVANCE TO CLINICAL PRACTICE: We suggest sampling from arterial or CVC lines rather than from the circuit line in a reversed connection during RCA-CRRT.

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