[Expression profile of circular RNA in inflammatory response in human bronchial epithelial cells induced by carbon black nanoparticles].

Objective: To explore the toxic effect of carbon black nanoparticles on human bronchial epithelial cells, and identify the differentially expressed circular RNA based on the full transcriptome high-throughput sequencing, so as to provide evidence for the development of biomarkers exposed to carbon black nanoparticles and their application on epigenetic toxicology. Methods: In June 2020, 16 HBE cells were treated with carbon black nanoparticles at concentrations of 20, 40 and 80 µg/ml, and 16 HBE cells without any intervention were used as the control group. The cytotoxicity of carbon black nanoparticles was detected by CCK8 and LDH experiments. Real-time quantitative fluorescent PCR (qRT-PCR) and ELISA were used to detect the changes of interleukin-6 (IL-6) and interleukin-8 (IL-6, IL-8) mRNA and protein levels of carbon black nanoparticles with concentration gradient after 72 h exposure. Western blot analysis was conducted to detect the expression levels of toll-like receptor 4 (TLR4), phosphorylated nuclear factor-κB (P-NF-κB), apoptosis-related speckled protein (ASC) and Caspase-1 associated with nuclear factor-κB. According to high-throughput sequencing results, differentially expressed Circrnas were screened and identified by qRT-PCR, and those with stable differentially expressed circrnas and the strongest association with the NF-κB pathway were selected for ring performance identification. Results: After being exposed to carbon black nanoparticles for 72 h, the activity of 16HBE cells decreased significantly (P<0.05), and the release of lactate dehydrogenase increased significantly (P<0.05). Compared with control group, mRNA expression levels of IL-6 and IL-8, protein levels of IL-6 and IL-8 were increased, and protein levels of TLR4, p-NF-κB, ASC and Caspase-1 were significantly up-regulated in 16 HBE cells of different concentrations, with statistical significance (P<0.05). Compared with the control group, a total of 492 differentially expressed circular Rnas (|log2 FC|>1) were detected. Among the 5 differentially expressed (P<0.05) circular Rnas, circ_002642 was selected as the object of subsequent research on circular Rnas, affter 72 hours of exposure to 80 µg/ml CBNPs, 16HBE cells showed signlficantly higher expression of circ_002642 (P<0.05) . Conclusion: Carbon black nanoparticles can induce differentially expressed circular RNAs associated with inflammatory response in human bronchial epithelial cells.

[Evaluation of the clinical manifestations of COVID-19 in patients with aplastic anemia undergoing immunosuppressive therapy: a prospective cohort study (NICHE)].

Objective: To investigate the clinical features of coronavirus disease 2019 (COVID-19) in patients with aplastic anemia (AA) undergoing immunosuppressive therapy (IST) . Methods: In this prospective cohort study, we collected the demographic and clinical data of patients with AA and COVID-19 from December 1, 2022, to January 31, 2023. We described the clinical features of COVID-19 among patients with AA and evaluated the effects of IST on the signs and severity of COVID-19. Results: A total of 170 patients with AA and COVID-19 were included. The common early symptoms, including fever, dizziness or headache, muscle or body aches, and sore throat, disappeared within 1-2 weeks. Approximately 25% of the patients had persistent fatigue within 2 weeks. Many patients experienced cough after an initial 1-3 days of infection, which lasted for more than 2 weeks. There were no differences in the duration of total fever episodes and maximum body temperature when patients were stratified according to whether or not they underwent IST, by IST duration, or by use of anti-lymphocyte globulin (ALG) (P>0.05). No differences were observed in the occurrence of symptoms in either the early or recovery stages when patients with AA were stratified according to whether or not they underwent IST, or by IST duration (P>0.05). However, patients who received ALG had fewer fever episodes within 1 week after infection (P=0.035) and more sore throat episodes within 2 weeks after infection (P=0.015). There were no other significant differences in clinical symptoms between patients who did and patients who did not receive ALG (P>0.05) . Conclusion: The majority of patients with AA and COVID-19 recovered within 2 weeks of noticing symptoms when treated with IST.

[A real-world study of 176 cases with aplastic anemia treated in outpatient].

Objective: To explore the diagnostic process and outcomes of patients with aplastic anemia (AA) who received outpatient treatment in a real-world setting. Methods: The diagnostic processes, treatment regimens, and outcomes of 176 patients with AA treated in outpatient centers from January 2018 to December 2019 were reviewed. Results: The median interval from the onset of symptoms to the first visit was 7 (5-120) months. Complaints during the first visit included bleeding (52.3% ) , anemia (51.7% ) , and infection (6.8% ) . For diagnosis, 168 patients (95.5% ) underwent bone marrow aspiration; however, only 22 of them (17.1% ) consented aspiration in multiple sites (sternum) . The completion rate of bone marrow biopsy was 85.1% (143/168) ; flow immunophenotype and karyotype analyses were performed on 59.5% (100/168) and 58.9% (99/168) of AA patients, respectively, and the culture of clonal forming units by bone marrow mononuclear cells was performed on 26.8% (45/168) of AA patients. The most preferred regimen was cyclosporine combined with androgen and levamisole (43.8% , 77 patients) , followed by cyclosporine combined with androgen (25.6% , 45 patients) . Cyclosporine alone was administered in 24 patients (13.6% ) and androgen alone in 16 patients (9.1% ) . Furthermore, 14 patients (7.9% ) did not consent to any drugs or only chose traditional Chinese medicine. The patients were divided according to the frequencies of follow-up: regular follow-up group (≥4 times/year, n=130) and irregular group (<4 times/year, n=46) . The former had a higher 6-month remission rate (52.5% vs 28.0% , P=0.005) , a greater high-quality remission rate in 12 months (40.7% vs 16.7% , P=0.027) , and a lower relapse rate in 24 months (4.4% vs 36.4% , P=0.001) . Conclusion: In real-world settings, bone marrow aspiration in multiple sites should be addressed in outpatient treatment for AA diagnostic work-up, including PNH clone screening, flow immunophenotype, chromosome karyotype analysis, and culture of clonal forming units. Patients with AA who follow regular visits were more likely to achieve high-quality remission and a lower relapse rate. Visits at least four times per year are recommended for AA patients undergoing outpatient treatment.

Dietary L-arginine supplementation enhances growth performance, intestinal antioxidative capacity, immunity and modulates gut microbiota in yellow-feathered chickens.

This study investigated the effects of dietary Arginine (Arg) on performance, intestinal antioxidative capacity, immunity, and gut microbiota in Chinese yellow-feathered chickens. One thousand two hundred 1-day-old female Qingyuan partridge chickens were randomly assigned to 5 groups with 6 replicates of 40 birds each. Chickens were fed diets with 5 levels of total Arg (8.5, 9.7, 10.9, 12.1, and 13.3 g/kg) without antibiotics for 30 d. The ADFI, ADG, and feed conversion ratio were improved with dietary Arg levels (P < 0.05). The proportions of CD3+ and CD4+/CD8+ lymphocytes responded in a linear (P < 0.05) manner and those of CD4+ in a linear or quadratic (P < 0.05) manner as dietary Arg levels increased. Dietary Arg level had a linear (P < 0.05) or quadratic (P < 0.05) effect on the gene expression of glutathione peroxidase 1, heme oxygenase 1, nuclear factor erythroid 2-related factor 2, and the activities of glutathione peroxidase and total antioxidative capacity in the jejunum and ileum. The relative expression of IL-1ß, myeloid differentiation primary response 88, and Toll-like receptor 4 decreased linearly (P < 0.05) in the ileum with increasing dietary Arg levels; secretory IgA contents were increased. In addition, sequencing data of 16S rRNA indicated that dietary Arg increased the relative abundance of Firmicutes phylum, Romboutsia and Candidatus Arthromitus genera, while decreased that of Clostridium sensu stricto 1. A diet containing 12.1 g Arg/kg promoted growth performance, intestinal antioxidation, and innate immunity and modulated gut microbiota in yellow-feathered chickens.

[Prevalence and risk factors of nonalcoholic fatty liver disease in patients with chronic hepatitis B receiving antiviral therapy].

Objective: To investigate the prevalence and risk factors of non-alcoholic fatty liver disease(NAFLD) in patients with chronic hepatitis B(CHB) receiving antiviral treatment. Methods: The cross-sectional study included 3 477 cases with CHB who received antiviral therapy. The prevalence of NAFLD was investigated, and then the risk factors were screened and analyzed by stepwise regression method in CHB patients with NAFLD as the dependent variable and the related influencing factors as independent variables. Results: The prevalence of NAFLD was 24.1% in CHB patients who received antiviral therapy. After adjusting for age and gender, central obesity (OR: 7.44, 95%CI: 6.06 ~ 9.14), hypertension (OR: 1.74, 95%CI: 1.51 ~ 2.20), and triglyceride (OR: 1.52, 95%CI: 1.18 ~ 1.96) were positively associated with NAFLD, and cirrhosis was negatively associated with NAFLD (OR: 0.42, 95%CI: 0.34 ~ 0.53). Patients with long-term antiviral therapy had increased risk of NAFLD. Conclusion: A significant proportion of CHB patients receiving antiviral therapy have suffered from NAFLD. Therefore, CHB patients receiving long-term antiviral treatment should pay more attention to the prevalence of NAFLD.

Parathyroid hormone independently predicts fracture, vascular events, and death in patients with stage 3 and 4 chronic kidney disease.

Doctors do not know whether treatment of high parathyroid hormone levels is linked to better outcomes in their patients with kidney disease. In this study, lower parathyroid hormone levels at baseline were linked to lower risk of fracture, vascular events, and death in people with kidney disease. PURPOSE: Chronic kidney disease (CKD) affects ~ 20% of older adults, and secondary hyperparathyroidism (HPT) is a common condition in these patients. To what degree HPT predicts fractures, vascular events, and mortality in pre-dialysis CKD patients is debated. In stage 3 and 4 CKD patients, we assessed relationships between baseline serum PTH levels and subsequent 10-year probabilities of clinical fractures, vascular events, and death. METHODS: We used Marshfield Clinic Health System electronic health records to analyze data from adult CKD patients receiving care between 1985 and 2013, and whose PTH was measured using a second-generation assay. Covariates included PTH, age, gender, tobacco use, vascular disease, diabetes, hypertension, hyperlipidemia, obesity, GFR, and use of osteoporosis medications. RESULTS: Five thousand one hundred eight subjects had a mean age of 68 ± 17 years, 48% were men, and mean follow-up was 23 ± 10 years. Fractures, vascular events, and death occurred in 18%, 71%, and 56% of the cohort, respectively. In univariate and multivariate models, PTH was an independent predictor of fracture, vascular events, and death. The hazards of fracture, vascular events and death were minimized at a baseline PTH of 0, 69, and 58 pg/mL, respectively. CONCLUSIONS: We found that among individuals with stage 3 and 4 CKD, PTH was an independent predictor of fractures, vascular events, and death. Additional epidemiologic studies are needed to confirm these findings. If a target PTH range can be confirmed, then randomized placebo-controlled trials will be needed to confirm that treating HPT reduces the risk of fracture, vascular events, and death.

Revealing the contribution of Cytochrome P450 to salt-sensitive hypertension using DNA microarray.

BACKGROUND: Salt sensitivity is an important cause of hypertension which is a major public health problem. This study aimed to investigate the contribution of Cytochrome P450 (CYP) to salt-sensitive hypertension with microarray data and bioinformatics analysis. METHODS: Gene expression data set GSE4800 was downloaded from Gene Expression Omnibus database, including 6 gene chips from 3 Dahl salt sensitive (DS) rat samples and 3 Lewis (LEW) rat samples. Raw data were preprocessed and normalized, and then differentially expressed genes (DEGs) were identified with Limma package. Interaction network was constructed by employing STRING (Search Tool for the Retrieval of Interacting Genes) tool. GO (Gene Ontology) enrichment analysis was performed using FuncAssociate tool and pathway analysis was carried out by EASE (Expressing Analysis Systematic Explorer). BLAST (Basic Local Alignment Search Tool) was applied to explore the sequence homology among CYP3A genes in rat and human based on multiple alignments. RESULTS: A total of 1264 DEGs, including 1082 up-regulated genes and 182 down-regulated genes were identified between DS and LEW samples. CYP3A2 and CYP3A9 were selected to construct the protein interaction network, which comprised 1653 pairs of interaction relationship among 100 genes. Functional analysis showed that CYP3A2 and CYP3A9 were most significantly related to oxidation reduction and metabolism of xenobiotics by cytochrome P450. Furthermore, the CYP3A2 and CYP3A9 genes in rats had high homology with genes CYP3A4and CYP3A5 in human beings. CONCLUSIONS: CYP3A4 and CYP3A5 may contribute to salt-sensitive hypertension in human which may act as biomarkers for this disease.

Propagation of Bleustein-Gulyaev waves in a prestressed layered piezoelectric structure.

Based on the theories of nonlinear continuum mechanics, piezoelectricity and elastic waves in solids, theoretical analysis of Bleustein-Gulyaev surface acoustic wave propagation in a prestressed layered piezoelectric structure are described. Numerical calculations are performed for the case that the layer and the substrate are identical LiNbO(3) except that they are polarized in opposite directions. It is found that an almost linear behavior of the relative change in phase velocity versus the initial stress is obtained for both surface electrically free and shorted cases. Potential applications in the design of acoustic wave devices are suggested.

Enhanced upper tropical tropospheric COS: impact on the stratospheric aerosol layer.

Carbonyl sulfide (COS) is considered to be a major source of the stratospheric sulfate aerosol during periods of volcanic quiescence. We measured COS at the tropical tropopause and find mixing ratios to be 20 to 50% larger than are assumed in models. The enhanced COS levels are correlated with high concentrations of biomass-burning pollutants like carbon monoxide (CO) and hydrogen cyanide (HCN). The analysis of backward trajectories and global maps of fire statistics suggest that biomass-burning emissions transported upward by deep convection are the source of the enhanced COS in the upper tropical troposphere.

Multiple drug resistance phenotype of human endothelial cells induced by vascular endothelial growth factor 165.

AIM: To investigate the effect of vascular endothelial growth factor 165 (VEGF165) on sensitivity of endothelial cells to anticancer drugs. METHODS: Human dermal microvessel endothelial cells (HDMEC) were incubated with anticancer drugs in the presence of VEGF165. Survival of endothelial cells was assayed by MTT method. DNA fragments of apoptosis were detected by agarose electrophoresis. Potential mechanisms underlying the effect of VEGF165 on endothelial cells were investigated with RT-PCR and Western blot analysis. RESULTS: VEGF165 induced the multidrug resistance phenotype of HDMEC to a wide variety of anticancer drugs such as epirubicin, cisplatin, etoposide, mytomycin C, vincristine, CPT-11, and taxol in vitro. This protective effect was partly due to the up-regulation of lung drug resistance protein (LRP) and multidrug resistance-associated protein (MRP), as well as the down-regulation of Bax protein induced by VEGF165. CONCLUSION: VEGF165 induced multidrug resistance phenotype of endothelial cells, which implicated the anti-angiogenic effect of anticancer drugs might depend on microenvironment of tumors in vivo.

A nonlinear anisotropic model for porcine aortic heart valves.

The anisotropic property of porcine aortic valve leaflet has potentially significant effects on its mechanical behaviour and the failure mechanisms. However, due to its complex nature, testing and modelling the anisotropic porcine aortic valves remains a continuing challenge to date. This study has developed a nonlinear anisotropic finite element model for porcine heart valves. The model is based on the uniaxial experimental data of porcine aortic heart valve leaflet and the properties of nonlinear composite material. A finite element code is developed to solve this problem using the 8-node super-parameter nonlinear shells and the update Lagrangian method. The stress distribution and deformation of the porcine aortic valves with either uniform and non-uniform thicknesses in closed phase and loaded condition are calculated. The results showed significant changes in the stress distributions due to the anisotropic property of the leaflets. Compared with the isotropic valve at the same loading condition, it is found that the site of the peak stress of the anisotropic leaflet is different; the maximum longitudinal normal stress is increased, but the maximum transversal normal stress and in-plane shear stress are reduced. We conclude that it is very important to consider the anisotropic property of the porcine heart valves in order to understand the failure mechanism of such valves in vivo.

Screening for CRX gene mutations in Chinese patients with Leber congenital amaurosis and mutational phenotype.

PURPOSE: To screen for possible disease-causing mutations in the CRX gene in Chinese patients with Leber congenital amaurosis (LCA) and to enrich the understanding of its mutational phenotype. METHODS: Genomic DNA was collected from 27 patients with LCA. The coding sequences of the CRX gene were analyzed using the PCR-heteroduplex-SSCP method. Mutations were confirmed by DNA sequencing. RESULTS: We identified two heterozygous variations in the CRX gene in two patients with LCA. One was a deletion (GCC-->-CC, A181D1bp) leading to a frameshift and protein truncation. This mutation was present in a patient with LCA, but not in his healthy parents. The ocular manifestations of this A181Delta1bp mutation are described. An intronic variation (IVS1-13G-->C) was found in a patient with LCA as well as in his healthy father. CONCLUSION: A heterozygous A181D1bp mutation in the CRX gene caused an LCA phenotype in a Chinese patient.

[Cloning the differentially expressed genes in the retina of rds mouse during the development of retinitis pigmentosa].

OBJECTIVE: To clone the differentially expressed genes in the retina of rds mouse (the animal model of congenital retinitis pigmentosa) during the disease development. METHODS: The retinal mRNA of rds mouse during the development of retinitis pigmentosa was analyzed by the mRNA differential display. The differentially expressed mRNA fragments were cloned and sequenced. RESULTS: There was obvious difference of gene expression between rds mouse and the control during the development of retinitis pigmentosa. Five differentially expressed bands were cloned and sequenced. One of those had 86% identity (132/154) with the sequence of the human cDNA DKFZp434D1227 from adult testis in GenBank, which was submitted lately (15-Oct-1999) and without much information. The other had lower identity with the sequences in GenBank. A highly expressed clone in the rds mouse on postnatal day 25 had the same length as another clone in the normal on postnatal day 37, which was not expressed in the rds mouse on day 37. The sequences of the two clones were identical in all but two base pairs. CONCLUSION: These results indicate that there are a lot of novel differentially expressed genes in the chronic processing diseases, such as retinitis pigmentosa.

Study on blood constitutive parameters in different blood constitutive equations.

A method is proposed to study the steady blood constitutive equation (BCE). With the method several BCEs are tested and Quemada, Bi-exponent and K-L equations are found to be well in agreement with the hemorheological characteristics of human and canine blood and these equations may be well used in hemorheology and hemodynamics. In addition, the potential clinical applications of some blood constitutive parameters (BCPs) are discussed. It is found that the hematocrit can significantly affect the BCPs: K(A) = alpha2/alpha1, Q(A) = eta0/eta(infinity), R(A) = etaA/eta(e) - 1, which means relative viscosities and they may be related to RBC aggregative level. Moreover, we also show that the parameters are related to the RBC aggregative strength and level.

Anti-tumor effect of angiogenesis inhibitor TNP-470 on the human nasopharyngeal carcinoma cell line NPC/HK1.

The efficacy and targeting cells of angiogenesis inhibitor TNP-470 on human squamous cell nasopharyngeal carcinoma (NPC) were investigated. The colorimetric MTT assay was used to evaluate the IC50 values of NPC/HK1 cells and human dermal microvascular endothelial cells (HDMEC) for TNP-470. An NPC human tumor model was built by tumor-bearing nude mice using the NPC cell line of NPC/HK1. TNP-470 (30 mg/kg s.c.) was injected every other day. The results showed that the IC50 of NPC/HK1 cells for TNP-470 was 3.8 times higher than that of HDMEC. A significant difference in tumor volume between control and treatment groups was found after 7 days of treatment and increased thereafter. At the end of the treatment, tumor volume was 773.7 +/- 287.1 mm3 (n = 8) in the control group versus 454.5 +/- 132.8 mm3 (n = 8) in the treatment group (p = 0. 013); the ratio of the mean tumor volume in treated animals to that of control animals was 0.587, resulting a 41.3% decrease in tumor growth. The necrotic area was larger in the treatment group. Physical toxicity did not result from the treatment. These studies suggest that angiogenesis inhibitor TNP-470 is effective in the treatment of squamous cell NPC without obvious toxicity.

Rectification on the inertial effects for co-axial cylinders rheometer.

The inertia of the fluid and the inner cylinder in co-axial cylinders rheometer have a great influence on the unsteady flow of non-Newtonian fluid. In the paper this phenomenon is studied minitely and a method to correct the measured results for an unsteady flow in the rheometer is proposed. It was found that the inertia effect of a fluid can be ignored when the gap between cylinders is smaller and the inertia effect of the inner cylinder can be represented with a vibration equation. Using the equation changes of Huang's blood constitutive parameters are observed.

[Finite element analysis of human tibia in vitro].

This investigation was aimed at the fatigue fracture of tibia that often occurs in soldiers, as well as in dancers and athletes. The data of ground reaction force(GRF) of soldiers were measured using a force platform in three common gaits: marching, parading and running. The stress distribution in tibia under these GRFs were analyzed with a FE model. The results showed that the smallest GRF(744.8N) is in quick marching, the next (1156.4N) in parading and the largest (1391.6N) in running. The stress distribution under GRF was mot uniform in the tibia. The maximum stresses occurred at a site 1/3 tibia length below the knee where tibia fracture is often seen clinically. The maximum stresses were 110 MPa and 115 MPa in parading and running respectively. This means that the tibial tractures in soldiers are mostly associated with stress, i.e. the greater the stress is, the higher the incidence of stress fracture comes about.

[Changes in blood constitutive equation parameters during shock in rabbits].

Based on the method which can more precisely obtain the constitutive parameters, we studied the changes of hemorphelogical characteristics of rabbits during shock and the effect of MN9200, a king of calcium channel anatogist injected into the veins of the rabbits. The results showed that shock induced a significant change in hemorheological index and NM9202 improved the condition.