ABSTRACT
Objective: To compare the difference in the effectiveness of ranibizumab (LU) and aflibercept (AF) in the treatment of diabetic retinopathy (DR). Methods: Ninety-four patients with DR admitted to Sunshine Union Hospital from August 2020 to February 2022 were selected for the study and were divided into LU group (n = 47) and AF group (n = 47) according to the random number table method. Both groups underwent 25G vitrectomy in our hospital, with LU injected into the vitreous before surgery in the LU group and AF in the AF group. Vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) in the pre-and post-injection atrial water were compared between the two groups, and the operative time, intraoperative bleeding, and the occurrence of medically induced fissures were recorded in both groups. In addition, the expression of best corrected visual acuity (BCVA), Central Macular Thickness (CMT), and inflammatory factors were compared before and after surgery. Finally, patients were counted for adverse reactions and prognosis of DR recurrence during treatment. Results: After injection, VEGF decreased and PEDF increased in both groups (P < .001). There were no differences in operative time (P = .604), intraoperative bleeding rate (P = .694), the incidence of medically induced fissure (P = .557), BCVA [P = .665 (T0), P > .999 (T1), P = .727 (T2)], and CMT [P = .688 (T0), P = .065 (T1), P = .148 (T2)] between the two groups, while IL-6, IL-8, and MMP-9 were lower in the AF group than in the LU group at 2 months after surgery (P < .001). Finally, there was no difference between both groups in terms of adverse effects and prognosis of DR recurrence rate (P = 1.000, .478). Conclusion: Both vitreous cavity injections of LU and AF can effectively reduce the expression of vascular-related factors in the atrial fluid of DR patients, but AF has a more significant inhibitory effect on the level of inflammatory factors in patients in the short term after treatment.
Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Receptors, Vascular Endothelial Growth Factor , Recombinant Fusion Proteins , Humans , Ranibizumab/therapeutic use , Diabetic Retinopathy/drug therapy , Diabetic Retinopathy/chemically induced , Vascular Endothelial Growth Factor A/therapeutic use , Angiogenesis Inhibitors/therapeutic use , Treatment OutcomeABSTRACT
OBJECTIVE: This study aimed to develop and validate a quantitative index system for evaluating the data quality of Electronic Medical Records (EMR) in disease risk prediction using Machine Learning (ML). MATERIALS AND METHODS: The index system was developed in four steps: (1) a preliminary index system was outlined based on literature review; (2) we utilized the Delphi method to structure the indicators at all levels; (3) the weights of these indicators were determined using the Analytic Hierarchy Process (AHP) method; and (4) the developed index system was empirically validated using real-world EMR data in a ML-based disease risk prediction task. RESULTS: The synthesis of review findings and the expert consultations led to the formulation of a three-level index system with four first-level, 11 second-level, and 33 third-level indicators. The weights of these indicators were obtained through the AHP method. Results from the empirical analysis illustrated a positive relationship between the scores assigned by the proposed index system and the predictive performances of the datasets. DISCUSSION: The proposed index system for evaluating EMR data quality is grounded in extensive literature analysis and expert consultation. Moreover, the system's high reliability and suitability has been affirmed through empirical validation. CONCLUSION: The novel index system offers a robust framework for assessing the quality and suitability of EMR data in ML-based disease risk predictions. It can serve as a guide in building EMR databases, improving EMR data quality control, and generating reliable real-world evidence.
Subject(s)
Data Accuracy , Electronic Health Records , Machine Learning , Electronic Health Records/standards , Humans , Risk Assessment/standards , Delphi TechniqueABSTRACT
Soil ingestion by livestock is common in grazing ecosystems, but few studies have been conducted to assess its effect on the animal organism. The topic is worthy of attention because these potential effects are likely to be enriched in the food chain and interfere with animal and human health. In this study, we present an indoor feeding trial conducted based on a completely randomized design to comprehensively evaluate the effects of simulated soil ingestion during grazing on nutrient digestibility, rumen fermentation, and microflora, and mineral deposition in the organs and tissues of sheep. Eighteen Mutton Merino crossbred sheep (42.7 ± 2.34 kg) were randomly allotted to three treatments and fed diets containing 0% (Control), 5% (SOIL5), and 10% (SOIL10) for 62 d, including a 7-d metabolism trial. It was found that soil intake altered the rumen fermentation in sheep, as evidenced by a decrease in total volatile fatty acids (VFA) and acetate concentrations in rumen fluid of 50.6% and 51.3%, respectively (p < 0.01), with soil proportion in the diet increased from 0% to 10%. Soil ingestion also reduced the species richness of rumen bacteria, with the relative abundance of Bacteroidetes decreasing significantly (p < 0.01), while that of Firmicutes and Proteobacteria increased considerably (p < 0.05). In terms of mineral elements deposition, higher levels of iron (Fe) were detected in the spleen and liver, and a higher concentration of copper (Cu) and zinc (Zn) in the liver were found in sheep fed a diet containing 5% soil compared to the other two groups (p < 0.05). Moreover, the concentrations of lead (Pb) in the liver and kidney, and arsenic (As) in the heart were also clearly increased after ingestion of soil (p < 0.05). Our findings indicate that although soil intake had no significant effect on the growth performance of sheep, it altered ruminal fermentation and increased the risk of excessive Fe, Pb, and As in their organism. This study supplies a theoretical basis for risk assessment of soil ingestion in grazing livestock.
Subject(s)
Arsenic , Ecosystem , Animals , Iron , Lead , Minerals , Rumen , SheepABSTRACT
OBJECTIVE: This paper aims to propose knowledge-aware embedding, a critical tool for medical term normalization. METHODS: We develop CODER (Cross-lingual knowledge-infused medical term embedding) via contrastive learning based on a medical knowledge graph (KG) named the Unified Medical Language System, and similarities are calculated utilizing both terms and relation triplets from the KG. Training with relations injects medical knowledge into embeddings and can potentially improve their performance as machine learning features. RESULTS: We evaluate CODER based on zero-shot term normalization, semantic similarity, and relation classification benchmarks, and the results show that CODER outperforms various state-of-the-art biomedical word embeddings, concept embeddings, and contextual embeddings. CONCLUSION: CODER embeddings excellently reflect semantic similarity and relatedness of medical concepts. One can use CODER for embedding-based medical term normalization or to provide features for machine learning. Similar to other pretrained language models, CODER can also be fine-tuned for specific tasks. Codes and models are available at https://github.com/GanjinZero/CODER.
Subject(s)
Natural Language Processing , Unified Medical Language System , Language , Machine Learning , SemanticsABSTRACT
BACKGROUND: Health information avoidance is common in real life, but because it is not always conducive to health promotion and maintenance, people often actively switch to health information acquisition. Understanding this process of active change can facilitate intervention in unreasonable avoidance behaviors. However, studies so far have mostly focused on why and how avoidance takes place, little is known about the process of active change from avoidance to acquisition. We thus use a grounded theory approach (GT) to explore how the active change takes place, and to generate a grounded theoretical framework capable of illustrating stages and influencing factors involved in the active change process. METHODS: Straussian grounded theory (Corbin & Strauss, 2015) was used to analyze data collected through semi-structured interviews with 30 adults (14 in good health, 11 with disease, 5 in other health status) who had experienced health information behavior change from avoidance to acquisition. These interviews focused on how the change occurred and what effected the change. RESULTS: The core category of Health Information Avoidance Change and 12 categories were identified and integrated to form a theoretical framework termed the Health Information Avoidance Change Model (HIACM). This model describes the process using five non-linear stage variables (initiation, preparation, action, maintenance, and abandonment) and seven moderating factor variables (cognitive change, social stimulus, beliefs and attitudes, intrapsychic literacy, social resources, information source, time and material resources). CONCLUSIONS: HIACM can be used to explain the process of active change from health information avoidance to health information acquisition. HIAC is a non-linear and holistic process, and it is necessary to dynamically analyze the impact of relevant factors and take targeted intervention measures in stages. HIAC is usually not only an individual behavior, but also a socialized behavior requiring the collaboration of individuals, families, health information providers, healthcare providers, and governments.
Subject(s)
Health Personnel , Adult , Grounded Theory , Health Personnel/psychology , HumansABSTRACT
Hypoxia leads to hypoxic pulmonary hypertension (HPH), causing right ventricular hypertrophy (RVH). RVH becomes a significant and nonnegligible public health issue in the world. In our study, we successfully established the HPH rat model and found that RVH happened in HPH, and then we observed an increased inflammation response in the heart tissue of HPH-induced RVH rats. Moreover, increased N-deacetylase-N-sulfotransferase-1 (NDST1) and decreased nuclear localized protein 1 (NULP1) were found in the heart tissue of HPH-induced RVH rats. An in vitro cell experiment showed that inhibition of NDST1 expression enhanced cell viability, reduced cell apoptosis, alleviated cardiomyocyte hypertrophy, decreased inflammation and increased phosphorylated AKT level, however, over-expression of NDST1 had opposite effects on these aspects. NULP1 reversed the effects of NDST1 on these regulations. Finally, we found that up-regulated NDST1 reduced NULP1 expression and down-regulated NDST1 increased NULP1 expression. Our study confirmed that inhibition of the NDST1/NULP1 pathway might contribute to the attenuation of HPH-induced RVH, and the mechanism may be related to the reduction of inflammation, cardiomyocyte apoptosis, and AKT phosphorylation.
Subject(s)
Hypertension, Pulmonary , Hypertrophy, Right Ventricular , Animals , Hypertension, Pulmonary/etiology , Hypertension, Pulmonary/metabolism , Hypertrophy, Right Ventricular/etiology , Hypertrophy, Right Ventricular/metabolism , Hypoxia/complications , Hypoxia/metabolism , Inflammation , Proto-Oncogene Proteins c-akt , Rats , SulfotransferasesABSTRACT
BACKGROUND: The coronavirus disease (COVID-19), a pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown its destructiveness with more than one million confirmed cases and dozens of thousands of death, which is highly contagious and still spreading globally. World-wide studies have been conducted aiming to understand the COVID-19 mechanism, transmission, clinical features, etc. A cross-language terminology of COVID-19 is essential for improving knowledge sharing and scientific discovery dissemination. METHODS: We developed a bilingual terminology of COVID-19 named COVID Term with mapping Chinese and English terms. The terminology was constructed as follows: (1) Classification schema design; (2) Concept representation model building; (3) Term source selection and term extraction; (4) Hierarchical structure construction; (5) Quality control (6) Web service. We built open access for the terminology, providing search, browse, and download services. RESULTS: The proposed COVID Term include 10 categories: disease, anatomic site, clinical manifestation, demographic and socioeconomic characteristics, living organism, qualifiers, psychological assistance, medical equipment, instruments and materials, epidemic prevention and control, diagnosis and treatment technique respectively. In total, COVID Terms covered 464 concepts with 724 Chinese terms and 887 English terms. All terms are openly available online (COVID Term URL: http://covidterm.imicams.ac.cn ). CONCLUSIONS: COVID Term is a bilingual terminology focused on COVID-19, the epidemic pneumonia with a high risk of infection around the world. It will provide updated bilingual terms of the disease to help health providers and medical professionals retrieve and exchange information and knowledge in multiple languages. COVID Term was released in machine-readable formats (e.g., XML and JSON), which would contribute to the information retrieval, machine translation and advanced intelligent techniques application.
Subject(s)
COVID-19 , Epidemics , Humans , Information Storage and Retrieval , Language , SARS-CoV-2ABSTRACT
A pepper quality detection and classification model based on transfer learning combined with convolutional neural network is proposed as a solution for low efficiency of manual pepper sorting at the current stage. The pepper dataset was amplified with data pre-processing methods including rotation, luminance switch, and contrast ratio switch. To improve training speed and precision, a network model was optimized with a fine-tuned VGG 16 model in this research, transfer learning was applied after parameter optimization, and comparative analysis was performed by combining ResNet50, MobileNet V2, and GoogLeNet models. It turned out that the VGG 16 model output anticipation precision was 98.14%, and the prediction loss rate was 0.0669 when the dropout was settled as 0.3, learning rate settled as 0.000001, batch normalization added, and ReLU as activation function. Comparing with other finetune models and network models, this model was of better anticipation performance, as well as faster and more stable convergence rate, which embodied the best performance. Considering the basis of transfer learning and integration with strong generalization and fitting capacity of the VGG 16 finetune model, it is feasible to apply this model to the external quality classification of pepper, thus offering technical reference for further realizing the automatic classification of pepper quality.
Subject(s)
Machine Learning , Neural Networks, ComputerABSTRACT
BACKGROUND: Kinesin superfamily proteins (KIFs) can transport membranous organelles and protein complexes in an ATP-dependent manner. Kinesin family member 15 (KIF15) is overexpressed in various cancers. However, the function of KIF15 in gastric cancer (GC) is still unclear. METHODS: GC patients' data from The Cancer Genome Atlas (TCGA) were analyzed by bioinformatics methods. The expression of KIF15 was examined in GC and paracarcinoma tissues from 41 patients to verify the analysis results. The relationship between KIF15 expression and clinical characteristics were also observed by bioinformatics methods. Kaplan-Meier survival analysis of 122 GC patients in our hospital was performed to explore the relationship between KIF15 expression levels and GC patients' prognosis. KIF15 was downregulated in GC cell lines AGS and SGC-7901 by transfecting a lentivirus-mediated shRNA plasmid targeting KIF15. In vitro, GC cell proliferation and apoptosis were detected by MTT assay, colony formation assay, and Annexin V-APC staining. In vivo, xenograft experiments were used to verify the in vitro results. Furthermore, Human Apoptosis Antibody Array kit was used to screen possible targets of KIF15 in GC cell lines. RESULTS: The bioinformatics results showed that KIF15 expression levels were higher in GC tissues than in normal tissues. IHC showed same results. High expression of KIF15 was statistical correlated with high age and early histologic stage. Kaplan-Meier curves indicated that high KIF15 expression predict poor prognosis in patients with GC. MTT assay and colony formation assay showed that KIF15 promote GC cell proliferation. Annexin V-APC staining found that KIF15 can inhibit GC cell apoptosis. Xenograft experiments reveal that downregulating KIF15 can inhibit GC tumor growth and promote GC apoptosis. Through detection of 43 anti-apoptotic proteins by the Human Apoptosis Antibody Array kit, it was confirmed that knocking down KIF15 can reduce seven anti-apoptotic proteins expression. CONCLUSIONS: Taken together, our study revealed a critical role for KIF15 to inhibit GC cell apoptosis and promote GC cell proliferation. KIF15 may decrease anti-apoptotic proteins expression by regulating apoptosis pathways. High expression of KIF15 predicts a poor prognosis in patients with GC. KIF15 might be a novel prognostic biomarker and a therapeutic target for GC.
ABSTRACT
BACKGROUND AND AIMS: Little is known about the mechanisms of IL-17 secreting T cells accumulation in HBV-transfected livers. Here, we investigated the role of the chemokines CCL17, CCL20 and CCL22 in this process. METHODS: Peripheral blood and liver tissues were obtained from 30 chronic hepatitis B (CHB) patients and 15 healthy volunteers and were evaluated by flow cytometric analysis and immunohistochemistry. Chemokine production by monocyte-derived dendritic cells (MoDCs) cocultured with HBV-transfected or untransfected Huh7 cells was measured by quantitative real-time PCR and enzyme-linked immunosorbent assay. The chemotactic activity of the culture supernatants was also tested. RESULTS: The proportions of IL-17 secreting CD4 (Th17) and CD8 (Tc17) T cells were both increased in liver and peripheral blood mononuclear cells of CHB patients compared to those in HVs. CHB patients showed higher intrahepatic levels of CCL17 mRNA, CCL22 mRNA, CCR6 mRNA and CCR4 mRNA than HVs. The expression of CCR6 and CCR4 on the surface of Th17 and Tc17 cells in CHB patients was also significantly higher than that in HVs. Significant correlations existed between the CCR4/CCR6 levels and both the alanine transaminase levels and HBV DNA loads. Contact between MoDCs and pBlue-HBV-transfected Huh7 cells induced the expression of CCL17 and CCL22 dependent on the dose of HBV DNA. However, CCL20 expression was lower in CHB patients than in HVs. Transwell experiments showed that upregulation of CCL17 and CCL22 enhanced the migration of IL-17 secreting T cells. CONCLUSIONS: Contact of HBV-transfected cells with MoDCs induces CCL17 and CCL22 chemokine production, which may favour the recruitment of Th17 and Tc17 cells to liver tissue in CHB. Our results reveal the mechanism of IL-17 secreting T cells recruitment to liver tissue and thus provide new immunotherapy targets for CHB patients.
Subject(s)
Hepatitis B virus , Interleukin-17 , Chemokine CCL17 , Chemokine CCL22 , Humans , Leukocytes, Mononuclear , Th17 CellsABSTRACT
There is a risk of iron overload in grazing livestock. However, the effects on nutrient absorption and rumen function induced by excessive iron have not been well understood. Therefore, the purpose of present study was to investigate the impact of over-load iron on growth performance, nutrient digestibility, blood biochemistry, rumen fermentation and bacterial communities in sheep. Twenty-four German Mutton Merino cross-bred sheep with weight (42.66 ± 2.34 kg BW) were randomly divided into 4 groups, each with 6 replicates and 1 sheep per replicate. The basal diet consisted of 60% Leymus chinensis hay and 40% concentrate. The sheep in 4 groups were fed the basal diets supplemented with 50 (Control), 500 (T1), 1,000 (T2) and 1,500 (T3) mg Fe/kg as ferrous sulphate monohydrate (FeSO4 ·H2 O) respectively. And the actual contents of iron in the diet were determined to be 457.68 (control), 816.42 (T1), 1,256.78 (T2) and 1,725.63 (T3) mg/kg respectively. The experiment lasted 62 days including a 7-day metabolism trial. During the whole experiment, the digestibility of dry matter, organic matter, neutral detergent fibre and acid detergent fibre showed a quadratic increase with increasing over-load iron levels (p < .05), and maximum responses were found with 500 mg/kg supplementation. However, the response of total VFA concentration showed a quadratic decrease, as did the concentrations of propionate, butyrate and valerate (p < .05). Serum total iron-binding capacity on day 30 showed a quadratic decrease with the increase in high-dose iron, while the serum iron content increased linearly at day 60 (p < .05). Excessive iron resulted in the change in bacterial communities. An increase in over-load iron linearly decreased the abundance of bacteria in the phylum Bacteroidetes (p < .05), but linearly increased the Firmicutes (p = .037) and Proteobacteria (p = .018). In addition, there was a quadratic effect (p = .003) on the Fibrobacteres, which was higher in the 500 and 1,000 mg/kg Fe-supplemented groups. At the genus level, there were quadratic effects on the abundances of Selenomonas_1 (p = .023) and Ruminococcaceae_UCG-014 (p = .016). Furthermore, feeding of iron linearly increased the relative abundances of Succiniclasticum and Succinivibrionaceae_UCG-002 (p < .05). These results indicate that increasing ferrous sulphate monohydrate in diets had no negative impact on the growth performance, but it changed nutrient digestibility, blood iron parameters, rumen fermentation and bacterial communities in sheep.
Subject(s)
Digestion/drug effects , Gastrointestinal Microbiome , Iron, Dietary/administration & dosage , Iron/administration & dosage , Iron/adverse effects , Sheep/physiology , Animal Feed/analysis , Animal Nutritional Physiological Phenomena , Animals , Bacteria/classification , Bacteria/drug effects , Diet/veterinary , Dietary Supplements , Dose-Response Relationship, Drug , Iron, Dietary/adverse effects , Male , Rumen/drug effects , Rumen/physiologyABSTRACT
BACKGROUND: Diabetes mellitus is a significant cause of death and disability worldwide and is a strong risk factor for acute coronary syndrome (ACS). Whether diabetes confers the same excess risk of ACS in both sexes is unknown. Therefore, we undertook a meta-analysis to estimate the relative risk (RR) for ACS associated with diabetes in men and women. METHODS: We systematically searched PubMed, Embase, and Cochrane Library databases for both case-control and cohort studies published between January 1, 1966, and January 1, 2015. Studies were included if they reported sex-specific estimates of the RR, hazard ratio, or odds ratio for the association between diabetes and ACS. We pooled the sex-specific RR and the ratio between women and men using a random-effect model with inverse-variance weighting. RESULTS: We included 9 case-control and 10 cohort studies with data for 10 856 279 individuals and at least 106 703 fatal and nonfatal ACS events. The pooled maximum-adjusted RR of ACS associated with diabetes was 2.46 (95% CI, 1.92-3.17) in women and 1.68 (95% CI, 1.39-2.04) in men. In patients with diabetes compared with those without diabetes, women had a significantly greater risk of ACS-the pooled women-to-men RR and the ratio of relative risks was 1.38 (95% CI, 1.25-1.52; P < .001), with no evidence of publication bias. CONCLUSIONS: The excess risk of ACS associated with diabetes is significantly higher in women than in men. This finding may be explained by more adverse cardiovascular risk profiles and suggests that further work is needed to clarify the relevant biological, behavioural, and social mechanisms.
Subject(s)
Acute Coronary Syndrome/etiology , Diabetes Mellitus, Type 2/complications , Cohort Studies , Female , Humans , Male , Risk Factors , Sex FactorsABSTRACT
AIM: To assess how pre-pregnancy body mass index (BMI) affects pregnancy outcome and total gestational weight gain (GWG) in a cohort of women with gestational diabetes (GDM). METHODS: Pregnant women at 24-28 gestational weeks diagnosed with GDM were classified as normal weight (pre-pregnancy BMI, 18.5-24.9 kg/m(2) ) or overweight (pre-pregnancy BMI, 25.0-29.9 kg/m(2) ). GWG was derived from the self-reported pre-pregnancy and pre-delivery weights, and analyzed using 2009 Institute of Medicine categories. RESULTS: A total of 106 GDM women were categorized as normal weight (n = 79) or overweight (n = 27). No statistically significant differences were found between the groups in terms of various obstetrical and neonatal outcomes. Higher pre-pregnancy BMI, however, was associated with excessive GWG during pregnancy (difference between groups, P = 0.013). Furthermore, pre-pregnancy BMI (OR, 0.529; 95%CI: 0.377-0.742; P = 0.000) and pre-pregnancy overweight (OR, 3.825; 95%CI: 1.469-9.959; P = 0.006) were independent factors of GWG. CONCLUSIONS: Among Chinese GDM women, overweight GDM mothers gain excessive weight during pregnancy. Regulation of pre-pregnancy bodyweight might be an appropriate precaution against excessive GWG.
Subject(s)
Body Mass Index , Diabetes, Gestational/epidemiology , Overweight/epidemiology , Pregnancy Outcome/epidemiology , Weight Gain , Adult , Asian People , China/epidemiology , Female , Gestational Age , Humans , Infant, Newborn , Overweight/complications , Pregnancy , Prospective StudiesABSTRACT
OBJECTIVE: Whether lowering glycosylated haemoglobin (HbA1c) level below 7.0% improves macro-vascular outcomes in diabetes remains unclear. Here, we aimed to assess the effect of relatively tight glucose control resulting in a follow-up HbA1c level of less or more than 7.0% on cardiovascular outcomes in diabetic patients. RESEARCH DESIGN AND METHODS: We systematically searched Medline, Web of science and Cochrane Library for prospective randomized controlled trials published between Jan 1, 1996 and July 1, 2015 that recorded cardiovascular outcome trials of glucose-lowering drugs or strategies in patients with type 2 diabetes mellitus. RESULTS: Data from 15 studies involving 88,266 diabetic patients with 4142 events of non-fatal myocardial infarction, 6997 of major cardiovascular events, 3517 of heart failure, 6849 of all-cause mortality, 2084 of non-fatal stroke, 3816 of cardiovascular death were included. A 7% reduction of major cardiovascular events was observed only when relatively tight glucose control resulted in a follow-up HbA1c level above 7.0% (OR 0.93, 95% CI 0.88-0.98; I(2) = 33%), however, the patients can benefit from reduction incidence of non-fatal myocardial infarction only when the follow-up HbA1c value below 7.0% (OR 0.85, 95% CI 0.74-0.96). Apart from the HbA1c value above 7.0% (OR 1.22, 95% CI 1.06-1.40), the application of thiazolidinediones (OR 1.39, 95% CI 1.14-1.69) also increased the risk of heart failure, while the gliptins shows neutral effects to heart failure (OR 1.14, 95% CI 0.97-1.34). CONCLUSIONS: Relatively tight glucose control has some cardiovascular benefits. HbA1c below 7.0% as the goal to maximize the cardiovascular benefits remains suspended.
Subject(s)
Cardiovascular Diseases/epidemiology , Diabetes Mellitus, Type 2/drug therapy , Glycated Hemoglobin/metabolism , Hypoglycemic Agents/therapeutic use , Cardiovascular Diseases/mortality , Diabetes Mellitus, Type 2/metabolism , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Heart Failure/epidemiology , Humans , Myocardial Infarction/epidemiology , Thiazolidinediones/therapeutic useABSTRACT
BACKGROUND: This study aimed to investigate the relationship between an intensified low-density lipoprotein-cholesterol (LDL-c) target of statin therapy and cancer risk. METHODS: Data from PUBMED, EMBASE, and the Cochrane Central Register of Controlled Trials as of September 2014 were searched for randomized controlled trials on statins. An intensified LDL-c target of <2.59 mmol/L (100 mg/dL) or a relative LDL-c reduction by at least 30% of the baseline was the primary criterion for all the trials that were included in this meta-analysis. The I(2) statistic was used to measure heterogeneity among the trials, and risk estimates were calculated for cancer incidence in this random-effect meta-analysis. RESULTS: Nine eligible studies were identified with 59,571 participants, of whom 5379 developed cancer during the follow-up period (2691 were given statins and 2688 were given control treatment). The intensified LDL-c target of statin therapy did not affect cancer incidence (odds ratio, 1.00; 95% confidence interval, 0.94 - 1.06; I(2) = 1.6%, p = 0.42), which included some common cancers. Subgroup analysis showed that neither the chemical properties nor the variety of the statins accounted for the residual variation in risk. CONCLUSIONS: The intensified LDL-c target of statin therapy had no effect on the overall incidence of cancer, including some common cancers. Therefore, intensified statin therapy does not need to be changed among adult clinical patients.
Subject(s)
Cholesterol, LDL/blood , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Neoplasms/chemically induced , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hypercholesterolemia/drug therapy , Incidence , Neoplasms/blood , Neoplasms/epidemiology , Randomized Controlled Trials as TopicABSTRACT
OBJECTIVES: To evaluate the psychological quality and its influencing factors of mine rescue staff. METHODS: A total of 310 on front line rescue staff from the mines in Tangshan were sampled by random cluster sampling method.Our own designed measurement tools for psychological quality, including Eysenck personality questionnaire (EPQ), attention test scale, willpower test scale and reactive agility test were used to investigate the psychological quality of mine rescue staff. All tests were conducted in quiet state.Other information including age, length of service for rescue, sex, education, smoking and drinking, and so on were collected at the same time. The mood and influencing factors on psychological quality of the rescue staff were also analyzed. RESULTS: The personality traits of mine rescue staff are close to the national norm.0.6% (2/310) staff showed weak willpower.20.7% (64/310) staff had unstable mood. The E and N factor scores in 20-29 years old group (12.7 ± 4.3 and 12.1 ± 5.1) were higher than 30-39, 40-49, 50-59 years old groups (E factor scores:11.4 ± 3.9, 10.6 ± 3.7 and 10.7 ± 3.9; N factor scores:11.0 ± 5.1, 9.4 ± 4.9 and 6.3 ± 3.4, respectively) (FE = 4.28, FN = 11.35, all P < 0.01) . The L factor score in 40-49 and 50-58 years old groups (13.0 ± 4.2 and 14.8 ± 3.6) were higher than 20-29 and 30-39 years old groups (11.5 ± 3.8 and 12.2 ± 3.8) (F = 6.08, P < 0.01) . Multivariate analysis found that the psychological quality of mine rescue staff was mainly influenced by the length of service (ß'E factor = -0.12, ß'willpower = -0.12), the amount of participating rescue (ß'P factor = 0.12, ß'N factor = -0.14), alerting duty (ß'L factor = 0.16, ß 'error number of target tracking = -0.161) , daily training (ß'attention = 0.22,ß'total number of aimed at the test = -0.18) and life events (ß'N factor = -0.14,ß'L factor = 0.13,ß'correct number of target tracking = -0.18). CONCLUSION: The mine rescue staff had high level psychological quality, length of service. the amount of participating rescue, and life events in the year effect the psychological quality of mine rescue staff.
Subject(s)
Emergency Responders/psychology , Mining , Rescue Work , Stress, Psychological , Adult , Cross-Sectional Studies , Humans , Male , Middle Aged , Quality of Life , Surveys and Questionnaires , Young AdultABSTRACT
OBJECTIVE: To investigate psychological stress and influence factors on the mine emergency rescue personnel. METHOD: 564 mine emergency rescue personnel from a rescue group were select as subjects, and 60 designers from a steel design institute were as controls. Self-made questionnaire and general job stress questionnaire were used to investigate the basic information, rescue history, psychosomatic symptoms, depression symptoms, daily job stress and negative emotions of emergency rescue personnel. SPSS17.0 software was used to analysis the psychological stress on the mine rescue personnel and its influence factors. RESULTS: The detection rate (41.94%) of depression symptoms in rescue team was higher than that of controls (24.90%). The score of daily job stress was higher than that of logistical support. The older age group with higher negative emotional and daily job stress than the younger. The highest negative emotion was in age group of more than 40 years old. The highest score of daily job stress was in ≤30 years old. The score of depression and psychosomatic symptoms were higher than those of the college and the above. The scores of depression in group of duration of rescue <10 years was higher than that of duration≥10 years. The score of daily job stress is the lowest in rescue for 1 to 2 times per year and the highest in group of simulation training once a week. The score of daily job stress and depressive symptoms were getting higher with the extension of combat duty time. Age, hours of combat duty, training times a week, education and life events were the main affecting fectors on mental health of mine rescuers. CONCLUSIONS: Mine rescuers have more psychological stress than generic population. The psychological stress of the mine crew is related to age, education, life events, training and combat readiness duty time.
Subject(s)
Emergency Responders/psychology , Mining , Rescue Work , Stress, Psychological , Adult , Cross-Sectional Studies , Depression , Disasters , Humans , Mental Health , Surveys and QuestionnairesABSTRACT
Simvastatin (SV) is a statin drug that can effectively control cholesterol and prevent cardiovascular diseases. However, SV is water-insoluble, and poor oral bioavailability (<5â¯%). Solid self-emulsifying carrier system is more stable than liquid emulsions, facilitating to improve the solubility and bioavailability of poorly soluble drugs. In the present study, a solid self-emulsifying carrier stabilized by casein (Cas-SSE) was successfully used to load SV to improve its solubility in water, by formulation selection and emulsification process optimization. Compared with oral tablets, the release of SV from Cas-SSE was significantly enhanced in artificial intestinal fluid. Furthermore, everted gut sac experiments indicated some water-soluble dispersing agents such as hydroxyethyl starch (HES), were not conducive to drug absorption. Pharmacokinetic studies suggested Cas-SSE without dispersing agent has much higher relative bioavailability (184.1â¯% of SV and 284.5â¯% of simvastatin acid) than SV tablet. The present work suggests Cas-SSE is a promising drug delivery platform with good biocompatibility for improving oral bioavailability of poorly water-soluble drugs.
Subject(s)
Biological Availability , Caseins , Drug Carriers , Emulsions , Simvastatin , Solubility , Simvastatin/pharmacokinetics , Simvastatin/chemistry , Simvastatin/administration & dosage , Caseins/chemistry , Caseins/pharmacokinetics , Administration, Oral , Animals , Drug Carriers/chemistry , Emulsions/chemistry , Rats , Male , Drug LiberationABSTRACT
Neutrophils are heterogeneous and plastic, with the ability to polarize from antitumour to protumour phenotype and modulate tumour microenvironment components. While some advances have been made, the neutrophil-targeting therapy remains underexplored. Activation of formyl peptide receptors (FPRs) by formylated peptides is needed for local control of infection through the recruitment of activated neutrophils while the potential contribution of antitumour activity remains underexplored. Here, we demonstrate that neutrophils can be harnessed to suppress tumour growth through the action of the formyl peptide (FP) on the formyl peptide receptor (FPR). Mechanistically, FP efficiently recruits neutrophils to produce reactive oxygen species production (ROS), resulting in the direct killing of tumours. Antitumour functions disappeared when neutrophils were depleted by anti-Ly6G antibodies. Interestingly, extensive T-cell activation was observed in mouse tumours treated with FP, showing the potential to alter the immune suppressed tumour microenvironment (TME) and further sensitize mice to anti-PD1 therapy. Transcriptomic and flow cytometry analyses revealed the mechanisms of FP-sensitized anti-PD1 therapy, mainly including stimulated neutrophils and an altered immune-suppressed tumour microenvironment. Collectively, these data establish FP as an effective combination partner for sensitizing anti-PD1 therapy by stimulating tumour-infiltrated neutrophils.
Subject(s)
Immunotherapy , Mice, Inbred C57BL , Neutrophils , Receptors, Formyl Peptide , T-Lymphocytes , Tumor Microenvironment , Animals , Neutrophils/drug effects , Neutrophils/immunology , Neutrophils/metabolism , Tumor Microenvironment/drug effects , Tumor Microenvironment/immunology , Mice , Immunotherapy/methods , Receptors, Formyl Peptide/metabolism , T-Lymphocytes/immunology , T-Lymphocytes/drug effects , Cell Line, Tumor , Reactive Oxygen Species/metabolism , Humans , Female , Neutrophil Activation/drug effects , Neoplasms/immunology , Neoplasms/drug therapy , Neoplasms/pathology , Lymphocyte Activation/drug effects , Programmed Cell Death 1 Receptor/metabolism , Programmed Cell Death 1 Receptor/immunologyABSTRACT
This study aims to investigate the roles of the Notch-Hes1 pathway in the advanced glycation end product (AGE)-mediated differentiation of neural stem cells (NSCs). We prepared pLentiLox3.7 lentiviral vectors that express short hairpin RNA (shRNA) against Notch1 and transfected it into NSCs. Cell differentiation was analyzed under confocal laser-scanning microscopy. The percentage of neurons and astrocytes was quantified by normalizing the total number of TUJ1+ (Neuron-specific class III ß-tubulin) and GFAP+ (Glial fibrillary acidic protein) cells to the total number of Hoechst 33342-labeled cell nuclei. The protein and gene expression of Notch-Hes1 pathway components was examined via western blot analysis and real-time PCR. After 1 week of incubation, we found that AGE-bovine serum albumin (BSA) (400 µg/mL) induced the astrocytic differentiation of cultured neurospheres and inhibited neuronal formation. The expression of Notch-Hes1 pathway components was upregulated in the cells in the AGE-BSA culture medium. Immunoblot analysis indicated that shRNA silencing of Notch1 expression in NSCs significantly increases neurogenesis and suppresses astrocytic differentiation in NSCs incubated with AGE-BSA. AGEs promote the astrocytic differentiation of cultured neurospheres by inhibiting neurogenesis through the Notch-Hes1 pathway, providing a potential therapeutic target for hyperglycemia-related cognitive deficits.