[Identification the key factor of pulmonary fibrosis following silica nanoparticles exposure based on bioinformatics analysis].

Objective: To investigate the main mechanisms of pulmonary fibrosis following silica nanoparticles (SiNPs) exposure through constructing the macrophage-fibroblast model in vitro, which simulated the process of pulmonary fibrosis. Methods: In January 2021, human mononuclear leukemia cells (THP-1) were treated with 0, 25, 50, 100 µg/ml SiNPs for 24 h. The supernatant of THP-1 cells was collected and applied to human embryonic lung fibroblast cells (MRC-5) which divided into control and low, medium and high dose groups at the logarithmic growth stage for 24 h. MRC-5 cell viability was detected by CCK8. The hydroxyproline (Hyp), interleukin 6 (IL-6), interleukin 1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) expression were detected in the supernatants of MRC-5. The changed proteins were detected by liquid-phase mass spectrometry in high dose group. GeneCard database were applied to identity the differential pulmonary fibrosis proteins in high dose group. Gene Ontology (GO) was performed to identity the key biological process in differential pulmonary fibrosis proteins of high dose group. The String database was used to construct the protein-protein interactions (PPI) network of differential pulmonary fibrosis proteins. The APP of CytoHubba was applied to calculate the key protein of differential pulmonary fibrosis proteins in PPI network. Correlation coefficients between key differential pulmonary fibrosis proteins were calculated using Pearson correlation analysis. Western blotting was applied to detect the expression of key proteins of differential pulmonary fibrosis proteins in different groups. Results: CCK8 results showed that MRC-5 cell viability was increasing in low, medium and high dose groups compared with control group (P<0.05). The expression levels of Hyp and IL-1ß in different group were increased compared with control group, the expression levels of IL-6 and TNF-α were increased in high dose group compared with control group (P<0.05). GeneCard database identified 26 differential pulmonary fibrosis proteins, which were mainly involved in extracellular matrix hydrolysis, cell inflammatory response, tissue repair, cell proliferation, inflammation response by GO analysis. The APP of CytoHubba was calculated that matrix metalloproteinase 9 (MMP9) and tissue inhibitor metalloproteinase 1 (TIMP1) played an important role in PPI network. The results of correlation analysis showed that MMP9 was correlated with the expression of matrix metalloproteinase 1 (MMP1), matrix metalloproteinase 3 (MMP3), TIMP1 and epidermal growth factor receptor (EGFR) (r=0.97, 0.98, 0.94, 0.93, P<0.05). Western blotting results showed that TIMP1 protein expression was increased in low, medium and high dose groups, while MMP9 protein expression was increased only in high dose group (P<0.05) . Conclusion: Differential expression proteins related with pulmonary fibrosis in MRC-5 cells mainly regulate biological processes of extracellular matrix hydrolysis, tissue repair, and cellular inflammation response following SiNPs exposure. MMP9 and TIMP1 may be the key proteins, which affected the fibrosis process in vitro pulmonary fibrosis model.

[Randomized controlled clinical trials of a quick screening model for symptomatic bacterascites for guided antibiotic therapy].

Objective: To investigate the clinical significance of a quick screening model for symptomatic bacterascites for guided antibiotic therapy. Methods: Data were collected prospectively from 24 cases of cirrhotic ascites who were newly admitted to Nanchang Ninth Hospital between September 2016 and February 2017. No clear indication for antibiotic treatment was used when the number of polymorphonuclear cells in ascites was <250 cells/mm3. A quick screening model for symptomatic bacterascites was determined by positivity and was randomly divided into the experimental (12 cases) and the control group (12 cases). The experimental group was given antibiotic treatment during the whole process, while the control group did not receive antibiotic treatment. The 10th day of treatment was the end point of the study. The treatment responses of the two groups were compared. The treatment response results were divided into three categories: complete response, partial response, and no response. The sum of complete and partial response rates was used to determine the response rate. The Mann-Whitney U test and Fisher's exact test were used to compare the treatment responses between groups. Results: The baseline conditions of gender, age, screening score, and disease severity were consistent between the two groups (P>0.05). On the 10th day of treatment, the number of complete responses between the experimental group and the control group was 1 to 0, the number of partial responses was 7 to 2, and the number of non-responses was 4 to 10, Z=-2.467, P=0.014. The response rate was significantly better in the experimental group than in the control group [66.7% (8/12) vs. 16.7% (2/12), P=0.036]. Conclusion: Guided antibiotic therapy is somehow important for the quick screening model for symptomatic bacterascites, and patients with cirrhotic ascites who test positive in this model can benefit from antibiotic therapy.

Prevalence of smoking among adolescents in China: an updated systematic review and meta-analysis.

OBJECTIVES: Smoking is a major public health problem worldwide. Estimates for smoking prevalence among adolescents in different regions and in the whole of China are important for the development of public health policies. We conducted a systematic review and meta-analysis to estimate the prevalence of smoking among youth in China. STUDY DESIGN: This is a meta-analysis study. METHODS: English (PubMed, EMBASE) and Chinese (China National Knowledge Internet, WANFANG Data, and CBM) databases were independently searched by two investigators from inception to May 2019. Random effects meta-analysis was conducted to estimate the pooled prevalence of smoking. Subgroup analysis and meta-regression were performed to investigate sources of heterogeneity. This study is registered with PROSPERO, number CRD42019130803. RESULTS: In total, 131 articles were included in the meta-analysis, with a total of 146 studies, involving 684,370 Chinese participants. The total prevalence of smoking among youth in mainland China was 8.17% (95% confidence interval: 6.97-9.45). Subgroup analysis showed that the geographic location and gender could significantly influence the prevalence of smoking. Meta-regression analyses revealed study year, sex ratio (male, %), and response rates did not contribute to the heterogeneity of the results (P-value >0.05). Sensitivity analysis showed that the results were statistically stable. CONCLUSION: This meta-analysis indicates that smoking is common among adolescents in China, and the rate varies between different regions. More practical and effective policies targeting adolescents are urgently needed.

[Clinical characteristics of 10 patients with uremic tumoral calcinosis].

Objective: To analyze the clinical characteristics of patients with uremic tumoral calcinosis (UTC). Methods: A total of 10 patients with UTC were enrolled in this study, who were admitted in the Department of Nephrology, China-Japan Friendship Hospital and Beijing Chuiyangliu Hospital from March 2013 to February 2019. Results: The average age of 4 male and 6 female patients on regular hemodialysis was (39.90±8.57) years. The average dialysis duration was(5.90±2.57) years. Three patients presented as single lesion of one joint, the other 7 patients as involvement of multiple large joints. Serum calcium was elevated in 2 patients,both over 2.75 mmol/L. Serum hyperphosphatemia was seen in all patients with average level 2.22 (1.94,2.44) mmol/L. Serum intact parathyroid hormone (iPTH) was remarkably increased in 9 patients with average level 1 348.0(854.8,1 800.0) ng/L, while only 1 patient reported slight elevation (92.4 ng/L).High-sensitivity C-reactive protein increased in all 10 patients with average 35.81 (17.60,74.20) mg/L. The imaging findings before treatment suggested that a large number of irregular masses of calcification shadows deposited in the soft tissue adjacent to the joints. The outlines of calcification were clear without significant bone absorption. Nine patients with severe secondary hyperparathyroidism (SHPT) were treated with parathyroidectomy, resulting in lesions diminishing or even disappearing. A total of 32 parathyroid glands were resected, and pathological results showed that 7 parathyroids were diffuse hyperplasia, 11 as diffuse/nodular hyperplasia, the rest 14 as nodular hyperplasia. At least one hyperplastic parathyroid gland was seen in each patient. Only 1 patient received medical therapy yet no obvious improvement was observed. Conclusion: UTC is a rare complication in patients on regular hemodialysis, which is usually associated with severe SHPT. Parathyroid surgery may improve the clinical outcome.

MicroRNA-24 attenuates vascular remodeling in diabetic rats through PI3K/Akt signaling pathway.

BACKGROUND AND AIMS: The vascular remodeling plays a crucial role in pathogenesis of diabetic cardiovascular complications. In this study, we intended to explore the effects and potential mechanisms of microRNA-24 (miR-24) on vascular remodeling under diabetic conditions. METHODS AND RESULTS: MiR-24 recombinant adenovirus (Ad-miR-24-GFP) was used to induce miR-24 overexpression either in carotid arteries or high glucose (HG)-induced vascular smooth muscle cells (VSMCs). Cell proliferation was analyzed using CCK-8 method. Cell migration was examined using wound-healing and transwell assay. mRNA and protein expressions of critical factors were, respectively, measured by real-time PCR and western blot as follows: qRT-PCR for the levels of miR-24, PIK3R1; western blot for the protein levels of PI3K (p85α), Akt, p-Akt, mTOR, p-mTOR, 4E-BP1, p-4E-BP1, p70s6k, p-p70s6k, MMP 2, MMP 9, collagen Ⅰ, as well as collagen Ⅲ. Carotid arteries in diabetic rats suffered balloon injury were harvested and examined by HE, immunohistochemical and Masson trichrome staining. The expression of miR-24 was decreased in HG-stimulated VSMCs and balloon-injured carotid arteries of diabetic rats, accompanied by increased mRNA expression of PIK3R1. The up-regulation of miR-24 suppressed VSMCs proliferation, migration, collagen deposition not only induced by HG in vitro, but also in balloon-injured diabetic rats, which were related to inactivation of PI3K/Akt signaling pathway. CONCLUSION: The up-regulation of miR-24 significantly attenuated vascular remodeling both in balloon-injured diabetic rats and HG-stimulated VSMCs via suppression of proliferation, migration and collagen deposition by acting on PIK3R1 gene that modulated the PI3K/Akt/mTOR axes.

[Analysis of risk factors and consequences for concurrent obstructive sleep apnea in chronic obstructive pulmonary disease patients].

Objective: To compare clinical characteristics between patients with chronic obstructive pulmonary disease (COPD) and COPD -OSA overlap, and to analyze the risk factors for OSA in patients with COPD. Methods: A total of 431 patients with COPD were divided into a COPD-OSA group with AHI>15 events/h or a COPD group with AHI ≤ 15 events/h according to the results of polysomnography, and their clinical characteristics were summarized. Risk factors for OSA overlap in COPD patients were identified by univariate and multivariate logistic regression analyses. Results: There were no significant differences in gender composition, dyspnea scale (mMRC) score, the numbers of acute exacerbations and hospitalizations in the last year, prevalence of coronary heart disease, or cor pulmonale or diabetes mellitus in the two groups (all P>0.05). Age, BMI, neck circumference, smoking index, COPD assessment test (CAT) score, the values of FEV(1) or FEV(1)%, FEV(1)/FVC ratios, and the prevalence of hypertension in the COPD-OSA group with AHI>15 events/h were significantly higher than in the COPD group with AHI ≤15 events/h, while the duration of COPD and the proportion of severe COPD were lower than the COPD group with AHI≤ 15 (P<0.05). The scores of Charlson Comorbidity Index, Epworth Sleepiness Scale (ESS) and Sleep Apnea Clinical Score (SACS) in the COPD-OSA group were significantly higher than in the COPD group with AHI≤ 15, with all P values<0.05. Risk factors for AHI>15 OSA coinciding in patients with COPD included BMI, neck circumference, ESS, SACS and CAT (P<0.05). Furthermore, BMI, ESS and CAT were independent risk factors for OSA in COPD patients (P<0.05). Compared with mild or moderate COPD cases, patients with severe COPD (FEV(1)%<50%) had a lower risk of having OSA (ß=-0.459, OR=0.632, 95% CI 0.401-0.997, P=0.048). Conclusions: Compared to COPD patients with AHI ≤ 15 events/h, OSA-COPD overlap patients (AHI>15 events/h) had a worse quality of life, more daytime sleepiness and higher prevalence of hypertension. BMI, ESS and CAT were independent risk factors for AHI>15 OSA in patients with COPD. The risk of having OSA in severe COPD patients was lower than cases with mild or moderate COPD.

[Application of three questionnaires in screening obstructive sleep apnea in patients with chronic obstructive pulmonary disease].

Objective: To evaluate the clinical value of three questionnaires [Sleep Apnea Clinical Score (SACS), Berlin Questionnaire (BQ), and Epworth Sleepiness Scale (ESS)] in screening obstructive sleep apnea (OSA) in patients with chronic obstructive pulmonary disease (COPD). Methods: A total of 198 patients with COPD were assessed the likelihood of OSA by using the SACS, BQ, ESS, which was confirmed by the overnight polysomnography (PSG). The receiver operating characteristic curve (ROC) and the calculated likelihood ratios were used to compare the values of three scoring systems in predicting OSA in COPD patients. Results: The patients had an average age of (65.5±9.3) years and 92.9% (184 cases) of which were male, 14 cases (7.1%) were female; 27 cases (13.6%) had a high probability of OSA by SACS assessment, 61 cases (30.8%) had a high probability screened by BQ, and 72 (36.4%) had OSA high probability by ESS. The diagnosis of OSA in 75 patients (37.9%) were confirmed by PSG. OSA did not be accurately predicted by ESS screening in patients with COPD, with a ROC curve area under the curve of 0.592 (95% CI: 0.509-0.674, P=0.053). BQ had an area under the ROC curve of 0.706 (95% CI: 0.626-0.779, P<0.001). However, the prediction of SACS was much better, with an area under the ROC curve of 0.810 (95% CI: 0.737-0.871, P<0.001). Conclusion: SACS is superior to BQ and ESS in predicting OSA in this group of patients with COPD.

[5-HT(2A) receptor/protein kinase C pathway in mediating long-term facilitation of carotid sinus nerve discharge in chronic intermittent hypoxia rats].

Objective: To explore the role of 5-HT(2A)R/PKC pathway in mediating long-term facilitation (LTF) of carotid sinus nerve (CSN) discharge in chronic intermittent hypoxia (CIH) rats. Methods: With number table, 24 adult SD rats were randomly divided into saline control group (group A, n=6), 5-HT(2A)R antagonist (ketanserin) group (group B, n=6), PKC inhibitor (PKC θ-pseudosubstrate) group (group C, n=6) and combined ketanserin with PKC θ-pseudosubstrate group (group D, n=6). All rats were placed into the animal chambers for CIH treatment, 8 h per day (from 9: 00 to 17: 00) for 4 consecutive weeks. 28 days later, 5 min × 3 times of stimulation with acute intermittent hypoxia (AIH) were given, after that, stable CSN discharge activities were recorded and compared before and after intravenous injection of saline (group A), ketanserin (group B), PKC θ-pseudosubstrate (group C) or ketanserin + PKC θ-pseudosubstrate (group D), respectively. Results: There were no significant difference in the baseline (before AIH stimulation) average peak amplitude of CSN discharge among the four groups (P>0.05). In group A, the amplitude of CSN discharge at 30 min and 60 min after AIH were (5.01 ± 0.53) µV and (4.95 ± 0.34) µV respectively, which were significantly higher than that before AIH (P<0.01). The results implied that the CSN LTF could be induced by AIH in CIH pre-treatment rats. In group B, the amplitude of CSN discharge at 30 min and 60 min after AIH were (3.79 ± 0.42) µV and (3.73 ± 0.46) µV, respectively, which were still significantly higher than that before AIH (P<0.01), showing that carotid sinus nerve LTF couldn't be completely blocked by 5-HT(2A)R antagonist in rats. After injection of PKC θ-pseudosubstrate or ketanserin + PKC θ-pseudosubstrate in group C or D, there were no significant differences in CSN discharge amplitude before and after AIH (P>0.01), suggesting that inhibition of PKC alone or 5-HT(2A)R/PKC pathway could completely block the LTF of CSN. Conclusion: 5-HT(2A)R/PKC pathway was involved in mediating long-term facilitation of carotid sinus nerve discharge in CIH rats.

Crohn's disease with positive Ziehl-Neelsen stain: Three case reports.

Because of the similarity of the clinical symptoms, endoscopic, and pathological features, the differential diagnosis between Crohn's disease (CD) and intestinal tuberculosis (ITB) remains difficult, especially in a high-incidence area of tuberculosis (TB). Here we reported three patients with positive Ziehl-Neelsen stain in endoscopic mucosal biopsy specimens. They had a poor response to anti-TB therapy but a good response to immunosuppresses, infliximab, or surgery, and were finally diagnosed as CD. It was not clear that they were CD concomitant with mycobacteria infection or CD induced by mycobacteria infection. Further studies including more clinical cases and related animal models are needed. Our cases highlight the importance of considering the presence of CD in patients with positive Ziehl-Neelsen stain, which were failure to respond to anti-TB treatment.

The reversal of the spontaneous exchange bias effect and zero-field-cooling magnetization in La1.5Sr0.5Co1-xFexMnO6: the effect of Fe doping.

The crystal structure, electronic structure and magnetic properties were systematically studied in a series of Fe-doped La1.5Sr0.5CoMnO6 double perovskites. The X-ray diffraction patterns of the samples are all refined with a rhombohedral (R3[combining macron]c) structure. The parameters a and c continuously increase with increasing Fe doping concentration x. X-ray photoelectron spectroscopy (XPS) spectra of the Mn, Co, and Fe 2p core levels, consistent with the soft X-ray absorption spectroscopy (XAS) spectra of Mn, Co, and Fe L2,3 edges, indicate that their valence states are Mn3+ and Mn4+, Co2+ and Co3+, and Fe3+, respectively. However, relative to samples with x ≤ 0.1, there is an abrupt change of photon energy in the Co- and Fe-2p XAS spectra for x ≥ 0.2, implying the spin state transition is from high to low. In addition, this is further confirmed by a comparison between the calculated effective spin moment from the paramagnetic data and the theoretical value. Interestingly, we demonstrate the reversal of both zero-field-cooling magnetization and the sign switching of the spontaneous exchange bias (SEB) with the doping concentration from magnetic measurements. The magnetization reverses from positive to negative with the temperature decreasing across the compensation temperature at the critical concentration x = 0.2. Meanwhile, the exchange bias field of the SEB reverses from large negative values to positive ones. Our findings allow us to propose that the spin state transition caused by inhomogeneity is considered to play an important role in the reversal of the magnetization and the SEB effect.

Pivotal role of glutathione depletion in eNOS uncoupling of LPS-Treated HUVECs.

The present study investigated the relationship between uncoupling of endothelial nitric oxide synthase (eNOS) and vascular endothelial cell (VEC) oxidative stress (OS) during sepsis and the role of eNOS glutathionylation in eNOS uncoupling of septic VECs. Human umbilical vein endothelial cells (HUVECs) cultured in vitro (EA.hy269 cell line) were incubated with Dulbecco's modified Eagle's medium (DMEM) (normal control group), lipopolysaccharide (LPS) (sepsis group), 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) (glutathionylation group), and LPS+ dithiothreitol (DTT) (deglutathionylation sepsis group). As result, compared with the DMEM group, malondialdehyde (MDA) level and uncoupling eNOS activity significantly increased in the LPS and BCNU groups. However, in the LPS + DTT group, only the NO level increased. Compared with the LPS group, MDA level, NO concentration, and normal functional eNOS activity significantly decreased, and uncoupling eNOS activity significantly increased in the BCNU group. In the LPS + DTT group, MDA level and uncoupling eNOS activity significantly decreased, and NO concentration and normal functional eNOS activity significantly increased. During sepsis, the main mechanism for VEC OS was eNOS uncoupling mediated by eNOS glutathionylation.

Medium density fibreboard production by hot pressing without adhesive using Triarrhena sacchariflora residue bio-pretreated by white-rot fungus Coriolus versicolor.

AIMS: To produce fibreboard with Triarrhena sacchariflora residue (TSR) without adhesive and understand the relationship between bio-pretreatment and mechanical property of fibreboard. METHODS AND RESULTS: White-rot fungus Coriolus versicolor was used to pretreat TSR, and biochemical and physical analysis were investigated by ultraviolet spectrophotometry, Fourier transform infrared spectroscopy and environmental scanning electron microscopy method. CONCLUSIONS: TSR was suitable to produce fibreboard without adhesive by bio-pretreatment with C. versicolor. The property of fibreboard became stronger by optimization of bio-pretreatment parameters, and the moduli of rupture and elasticity of fibreboard were increased to 18·12 MPa and 4·3 GPa, respectively, which were close to national standard of medium-density fibreboard with adhesive. Bio-pretreated TSR increased the mechanical properties of fibreboard because of 1·4-fold content of polysaccharide and 1·15 U g(-1) laccase, more hydroxyl group and more porous surface structure than that of untreated TSR. SIGNIFICANCE AND IMPACT OF THE STUDY: TSR-based fibreboard production without adhesive eliminated potential formaldehyde gas emission.

Lack of association between endothelial nitric oxide synthase gene polymorphisms with vasculitis: a meta-analysis.

OBJECTIVES: We carried out this meta-analysis to evaluate the relationship between eNOS polymorphisms (G894T, T-786C, and intron-4ba) and vasculitis. METHODS: We systematically searched PubMed, EMBASE and the Cochrane Library for related genetic association studies. The associations between the G894T, T-786C and intron 4ba polymorphisms of eNOS and vasculitis were conducted using the recessive model and the dominant model. Odds ratio (OR) with 95% confidence interval (CI) of each study were calculated. Cochran's Q test was used to evaluate the between-study heterogeneity. RESULTS: A total of 17 studies were included in our study. Twelve studies with 1213 cases and 1499 controls were included in the G894T association study. The pooled OR of T allele compared to C allele in recessive model was 1.19 (95%CI: 0.76-1.87, p=0.44) in dominant model and was 1.25 (95%CI: 0.70-2.23, p=0.56) in recessive model, respectively. Nine studies with 910 cases and 1062 controls were included in the intron -4ba association study. The pooled OR of b allele compared with intron-4a allele was 1.02 (95%CI: 0.60-1.72, p=0.95) in dominant model and was 0.84 (95%CI: 0.58-1.21, p=0.35) in recessive model. No association was found between T-786C and vasculitis in both the dominant 0.81(95% CI: 0.59-1.11, p=0.19) and recessive model 0.87 (95%CI: 0.55-1.36, p=0.53). CONCLUSIONS: The eNOS G894T, T-786C and intron4ba polymorphisms are not associated with vasculitis.

Current evidence on the relationship between murine double minute 2 T309G polymorphism and esophageal cancer susceptibility.

The relationship between murine double minute 2 (MDM2) T309G polymorphism and esophageal cancer risk has been discussed with discrepant results. The aim of our study is to investigate the systematic association between the potentially functional MDM2 T309G polymorphism and esophageal cancer risk. Eligible studies were included through searching the databases of PubMed, EMBASE, and Chinese National Knowledge Infrastructure (up to April 2014). The crude odds ratio (OR) and 95% confidence interval (CI) were used to estimate the strength of the association. Six published case-control studies, including 1899 cases and 3016 controls, were identified. Overall, our study suggested that MDM2 T309G polymorphism was significantly associated with increased risk of esophageal cancer (TT vs. GG: OR = 0.77, 95% CI = 0.65-0.90, P = 0.002; T vs. G: OR = 0.88, 95% CI = 0.81-0.96, P = 0.002). In subgroup analyses stratified by source of controls, ethnicity, and quality score assessment, respectively, similar results were obtained (TT vs. GG: OR = 0.65, 95% CI = 0.48-0.89, P = 0.007 for hospital-based studies; T vs. G: OR = 0.90, 95% CI = 0.81-0.99, P = 0.04 for population-based studies; and T vs. G: OR = 0.85, 95% CI = 0.78-0.93, P = 0.004 for Asians). The results of Begg's test and Egger's test did not suggest publication bias in the studies. Therefore, the MDM2 T309G polymorphism may be significantly associated with increased esophageal cancer risk, especially among Asians.

A single nucleotide polymorphism of the TNRC9 gene associated with breast cancer risk in Chinese Han women.

A single nucleotide polymorphism (SNP) in the TNRC9 gene was identified as a breast cancer susceptibility genetic variant in recent genome-wide association studies of women of European ancestry. We investigated whether TNRC9 polymorphisms are associated with risk of breast cancer in Chinese women of the Han nationality. We genotyped the SNPs rs3803662, rs1362548, rs1123428 in 870 women, including 388 breast cancer patients and 482 healthy controls, via the PCR-single strand conformation polymorphism procedure and by sequence detection. We found that the T allele and the TT genotype of the SNP rs38033662 is significantly associated with risk for breast cancer in Chinese Han women; however, no significant association was found for rs1362548 or rs1123428. We conclude that SNP rs3803662 is a putative risk factor for breast cancer in Chinese Han women.

Ensemble downscaling in coupled solar wind-magnetosphere modeling for space weather forecasting.

Advanced forecasting of space weather requires simulation of the whole Sun-to-Earth system, which necessitates driving magnetospheric models with the outputs from solar wind models. This presents a fundamental difficulty, as the magnetosphere is sensitive to both large-scale solar wind structures, which can be captured by solar wind models, and small-scale solar wind "noise," which is far below typical solar wind model resolution and results primarily from stochastic processes. Following similar approaches in terrestrial climate modeling, we propose statistical "downscaling" of solar wind model results prior to their use as input to a magnetospheric model. As magnetospheric response can be highly nonlinear, this is preferable to downscaling the results of magnetospheric modeling. To demonstrate the benefit of this approach, we first approximate solar wind model output by smoothing solar wind observations with an 8 h filter, then add small-scale structure back in through the addition of random noise with the observed spectral characteristics. Here we use a very simple parameterization of noise based upon the observed probability distribution functions of solar wind parameters, but more sophisticated methods will be developed in the future. An ensemble of results from the simple downscaling scheme are tested using a model-independent method and shown to add value to the magnetospheric forecast, both improving the best estimate and quantifying the uncertainty. We suggest a number of features desirable in an operational solar wind downscaling scheme. KEY POINTS: Solar wind models must be downscaled in order to drive magnetospheric models Ensemble downscaling is more effective than deterministic downscaling The magnetosphere responds nonlinearly to small-scale solar wind fluctuations.

Entropy-based information gain approaches to detect and to characterize gene-gene and gene-environment interactions/correlations of complex diseases.

For complex diseases, the relationship between genotypes, environment factors, and phenotype is usually complex and nonlinear. Our understanding of the genetic architecture of diseases has considerably increased over the last years. However, both conceptually and methodologically, detecting gene-gene and gene-environment interactions remains a challenge, despite the existence of a number of efficient methods. One method that offers great promises but has not yet been widely applied to genomic data is the entropy-based approach of information theory. In this article, we first develop entropy-based test statistics to identify two-way and higher order gene-gene and gene-environment interactions. We then apply these methods to a bladder cancer data set and thereby test their power and identify strengths and weaknesses. For two-way interactions, we propose an information gain (IG) approach based on mutual information. For three-ways and higher order interactions, an interaction IG approach is used. In both cases, we develop one-dimensional test statistics to analyze sparse data. Compared to the naive chi-square test, the test statistics we develop have similar or higher power and is robust. Applying it to the bladder cancer data set allowed to investigate the complex interactions between DNA repair gene single nucleotide polymorphisms, smoking status, and bladder cancer susceptibility. Although not yet widely applied, entropy-based approaches appear as a useful tool for detecting gene-gene and gene-environment interactions. The test statistics we develop add to a growing body methodologies that will gradually shed light on the complex architecture of common diseases.

[Comparison of the clinical outcomes of haploidentical and matched-sibling donor stem cell transplantation for T cell acute lymphoblastic leukemia in complete remission].

Objective: To compare the efficacy of haplotype hematopoietic stem cell transplantation (HIDT) and sibling matched hematopoietic stem cell transplantation (MSDT) in the treatment of complete remission (CR) acute T-lymphoblastic leukemia (T-ALL) . Methods: We retrospectively analyzed the clinical characteristics and outcomes of 98 patients who underwent HSCT in Hebei Yanda Ludaopei hospital with HID (n=81) or ISD (n=17) between May 2012 and May 2016. Results: The incidence of grades 2-4 and 3-4 acute-versus-host disease 100 days after HSCT were 51.9% (95% Confidence interval [CI] 42.0%-64.0%) vs 29.4% (95% CI 14.1%-61.4%) (P=0.072) and 9.8% (95% CI 5.1%-19.1%) vs 11.8% (95% CI 3.2%-43.3%) (P=1.000) for HIDT and MSDT. The 100-day cumulative incidences of CMV and EBV viremia were 53.1% (95% CI 43.3%-65.2%) vs 29.4% (95% CI 14.1%-61.4%) (P=0.115) and 35.8% (95% CI 26.8%-47.9%) vs11.8% (95% CI 3.2%-43.3%) (P=0.048) . The 5-year overall survival, leukemia-free survival, cumulative incidences of relapse, and no-relapse mortality were 60.5% (95% CI 5.4%-49.0%) vs 68.8% (95% CI 11.8%-40.0%) (P=0.315) , 58.0% (95% CI 5.5%-46.5%) vs 68.8% (95% CI 11.8%-40.0%) (P=0.258) , 16.1% (95% CI 9.8%-26.4%) vs 11.8% (95% CI 3.2%-43.3%) (P=0.643) , 25.9% (95% CI 17.9%-37.5%) vs 19.4% (95% CI 6.9%-54.4%) (P=0.386) for HIDT and MSDT, respectively. Conclusion: HID could be a valid alternative donor for patients with T-ALL in CR lacking an identical donor.

[CART therapy followed by allo-HSCT for patients with B-cell acute lymphoblastic leukemia relapsing after the first hematopoietic stem cell transplantation].

Objective: To study the clinical efficacy of chimeric antigen receptor T-cell (CART) treatment followed by a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with B-cell acute lymphoblastic leukemia (ALL) who relapsed following the first HSCT. Methods: Retrospective analysis of the clinical characteristics and prognosis of 41 patients with B-cell ALL who received a second allo-HSCT from October 2015 to June 2020 in Hebei Yanda Lu Daopei Hospital. After the first HSCT, all patients received CD19-CART, or CD22-CART treatment following a relapse of bone marrow morphology or extramedullary leukemia. Results: A total of 41 patients (male, 21; female, 20) were included in this study. The median age at the second HSCT was 16 (3-46) years. There were 31 cases of bone marrow recurrence (75.6%) , 5 cases of extramedullary recurrence (12.2%) , and 5 cases of bone marrow and extramedullary recurrences (12.2%) . After relapse, 35 patients (85.4%) received CD19-CART treatment, 2 patients received CD22-CART treatment (4.9%) , and 4 patients received CD19-CART and CD22-CART treatments (9.8%) . The expected 3-year overall survival (OS) , leukemia-free survival, cumulative relapse incidence, and non-relapse mortality (NRM) of patients after the second HSCT were 48.9% (95%CI 23.0%-70.6%) , 41.8% (95%CI 17.3%-64.9%) , 8.8% (95%CI 2.9%-26.4%) , and 51.1% (95%CI 31.2%-83.6%) , respectively. The 1-year OS of patients who relapsed ≤6 months and >6 months after the first HSCT were 45.0% (95%CI 12.7%-73.5%) and 75.0% (95%CI 51.4% -88.8%) (P=0.017) , respectively. Conclusion: CART bridging in the second HSCT enables some B-cell ALL patients who relapsed after the first HSCT to achieve long-term survival. However, because of the high NRM, further modifications could help improve the outcome.

Adipogenesis in ducks interfered by small interfering ribonucleic acids of peroxisome proliferator-activated receptor gamma gene.

Peroxisome proliferator-activated receptor gamma (PPARgamma) participates in adipocyte differentiation and maintenance, including the promotion of lipid storage in mammals. In the present study, 3 duck PPARgamma small interfering RNA (siRNA) expression plasmids were constructed to investigate the effect of downregulating the expression of PPARgamma on adipogenesis and fat accumulation in ducks. The results indicate that the 3 siRNA specific for conserved regions of PPARgamma can effectively inhibit expression of PPARgamma. It was demonstrated that the expression of lipoprotein lipase and adipocyte fatty acid-binding protein in duck adipose tissue is repressed when the expression of PPARgamma is downregulated by siRNA. At the same time, the weight of abdominal fat at 21 and 35 d of age is decreased significantly (P < 0.05) compared with the control. However, the triglyceride levels in serum and muscle are not affected when the mRNA of PPARgamma is repressed. The current study indicates that the suppression of PPARgamma reduces abdominal fat deposition and regulates adipogenesis in ducks.