Exosomal MFI2-AS1 sponge miR-107 promotes non-small cell lung cancer progression through NFAT5.

BACKGROUND: Non-small cell lung cancer is a heterogeneous disease driven by extensive molecular alterations. Exosomes are small vesicles with diameters ranging from 30 to 150 nm released by various cell types and are important mediators of information transmission in tumor cells. Exosomes contain proteins, lipids, and various types of nucleic acids, including miRNAs and even DNA and RNA. MFI2 Antisense RNA 1 (MFI2-AS1) is a long noncoding RNA known to promote cell proliferation, metastasis and invasion in a variety of malignancies. METHODS: The relative expression of MFI2-AS1 in NSCLC tissues was examined using RNA fluorescence in situ hybridization (FISH) staining. Transwell migration and wound healing assays were used to analyze cell migration and invasion abilities. Tube formation is used to assess angiogenic capacity. CCK8 was used to assess cell proliferation ability. RNA immunoprecipitation (RIP) experiments confirmed that MFI2-AS1 acts as a competing endogenous RNA (ceRNA) for miR-107. Dual-luciferase reporter assays were used to identify potential binding between MFI2-miRNA and target mRNA. In vivo experiments were performed by injecting exosomes into subcutaneous tumors to establish animal models. RESULT: Exosomal MFI2-AS1 increases NFAT5 expression by sponging miR-107, which in turn activates the PI3K/AKT pathway. We found that the MFI2-AS1/miR-107/NFAT5 axis plays an important role in exosome-mediated NSCLC progression, is involved in pre-metastatic niche formation, and can be used as a blood-based biomarker for NSCLC metastasis. CONCLUSION: We demonstrate that MFI2-AS1 is upregulated in exosomes secreted by metastatic NSCLC cells and can be transferred to HUVECs, promoting angiogenesis and migration.

Evaluating the association between MPDZ-NF1B rs1324183 and keratoconus in an independent northwestern Chinese population.

BACKGROUND: Keratoconus (KC) is a complex, non-inflammatory corneal degenerative disease. Although numerous studies have analyzed the correlation of SNP rs1324183, which located in MPDZ-NF1B gene, and KC in different populations, only few findings were repeated. In this study, to evaluate the association between rs1324183 and KC in a new independent Chinese population, we performed a replication study of the significantly associated rs1324183. METHODS: In total of 114 unrelated KC patients and 88 unrelated controls were recruited from Ningxia, China. We detected the genotypes and alleles of rs1324183 using PCR technology and Sanger sequencing and also analyzed the association between this locus and KC, its clinical parameters by statistical methods. RESULTS: The frequency of genotype AA (11, 9.6%) and genotypes containing allele A (47, 41.2%) of rs1324183 in KC were both higher than those of the control group. And genotype AA of rs1324183 conferred a higher risk of KC (OR > 1). Moreover, corneal parameter Belin/Ambrósio enhanced ectasia display final D value (BAD-D) had significant correlation (p = 0.002) with AA genotype of rs1324183 in KC. CONCLUSIONS: Our replication study indicates that the results of rs1324183 associated with KC in our population is robust and further better illustrates the significance of BAD-D as a diagnostic indicator for KC. rs1324183 should be considered as the first genetic mark of KC risk in its future diagnosis.

Robust Control of a New Asymmetric Teleoperation Robot Based on a State Observer.

This study is mainly about the designation of a new type of haptic device and an asymmetric teleoperation robot system. Aiming at the problems of tracking and transparency of an asymmetric teleoperation system, a robust control algorithm based on a state observer was proposed. The Haptic Device was designed and was chosen as the master-robot of the system. The Baxter dual-arm robot was chosen as the slave-robot of the system. The simulation experiment of robust control based on a state observer of the asymmetric teleoperation robot was carried out. The experiment results showed that the maximum values of displacement tracking errors in three directions x, y, and z are 0.02 m, 0.01 m, and 0.015 m, respectively. Compared with single- joint PID control, the performance of the new control algorithm is improved. The force feedback experiment on the real asymmetric teleoperation robot system was carried out. The results showed that the force feedback wave is consistent with the actual situation and showed that the robust control algorithm proposed is superior to PID. Therefore, the algorithm perfectly satisfied the system. The experiment parameters also demonstrate that the haptic device satisfies the design requirements of the asymmetric teleoperation robots system and the industry standards.

Epidemiology and risk factors of chronic obstructive pulmonary disease in Suzhou: a population-based cross-sectional study.

BACKGROUND: The prevalence of chronic obstructive pulmonary disease (COPD) in Suzhou remains still unknown. The aim of this study was to quantify the disease burden and assess the risk factors of COPD. METHODS: This was a population-based, cross-sectional study of adults aged 40 years and older in Suzhou. A total of 4,864 adults were identified from June 2018 to December 2018 and 4,725 adults were finally recruited. Subjects underwent post-bronchodilator spirometry and were diagnosed according to the 2018 Global Initiative for Chronic Obstructive Lung Disease (GOLD). RESULTS: The data from 4,725 adults were ultimately included in the final analysis. The overall prevalence of COPD in subjects aged 40 and older was 12.4%, while it was 12.3% in men and 12.5% in women. Risk factors identified by multivariable logistic analysis were age (P<0.05, OR =2.29, 95% CI, 1.83-2.88) and underweight (BMI <18.5 kg/m2) (P<0.05, OR =1.57, 95% CI, 1.01-2.44). COPD patients also displayed weaker grip strength (P<0.001). Approximately half (50.7%) the COPD patients were asymptomatic, and compared with asymptomatic COPD patients, symptomatic COPD patients were older (69.5 vs. 67.2, P<0.05), smoked more frequently (12.1 vs. 7.1 pack year, P<0.05), had a more severe GOLD stage (stage I 27.0% vs. 39.4%, stage II 50.2% vs. 46.8%, stage III 17.0% vs. 11.1%, stage IV 5.8% vs. 2.7%, P<0.05), and a worse lung function index (FEV1, FVC, PEF, FEF25, FEF50, FEF75, FEF2575) (P<0.05). CONCLUSIONS: COPD was found to be highly prevalent in adults aged 40 years and older in Suzhou. Age and underweight were major risk factors of COPD. Half of the COPD patients were asymptomatic, and displayed decreased lung function upon the onset of respiratory symptoms. Therefore, spirometry screening is essential for the early detection and management of COPD.

Efficacy of sublingual immunotherapy for allergic asthma: retrospective meta-analysis of randomized, double-blind and placebo-controlled trials.

BACKGROUND: Allergen-specific immunotherapy (SIT) is the only available curative choice with a disease-modifying effect against respiratory allergies. The efficacy of SIT via the sublingual route was demonstrated by a number of clinical trials. This meta-analysis was performed to investigate the clinical efficacy and safety of sublingual-specific immunotherapy (SLIT) for allergic asthma. METHODS: PubMed, EMBASE and the Cochrane Central Register of Controlled Trials were searched for randomized, double-blind and placebo-controlled (DBPC) trials evaluating the efficacy and safety of SLIT on allergic asthma. Subgroup analyses were performed according to age, type of allergen and duration of SLIT treatment. RESULTS: Sixteen randomized DBPC trials comprising 794 patients in total met the inclusion criteria. The results suggest that SLIT significantly reduces both symptom [standardized mean difference (SMD), -0.74; P=0.006] and medication scores (SMD, -0.78; P=0.02) compared with placebo. SLIT offers a better clinical response in mite sensitive asthmatics but without confirmed proof from subgroup analyses. Prolonged duration of treatment for more than 12 months brings no additive effects. Improvement in the skin prick test was also observed following immunotherapy. There was no consistent effect on forced expiratory volume in 1 s, serum levels of antigen-specific immunoglobulin G4 and immunoglobulin E in the treated group. The risk of adverse effects was relative risk 2.23 (P=0.01). CONCLUSIONS: SLIT is safe and clinically effective in reducing symptoms and medication use for allergic asthma. Our subgroup analyses failed to identify a disproportionate benefit of SLIT in any specific group of asthmatics, but some possible trends did emerge.

CD39/CD73 and the imbalance of Th17 cells and regulatory T cells in allergic asthma.

In the immune system, CD4+CD25+Foxp3+ regulatory T cells (Tregs) maintain self­tolerance and Th17 cells mediate inflammatory responses. CD39 is expressed on the surface of a subset of naturally occurring human Tregs that are important in constraining pathogenic Th17 cells. Additional studies have shown that Tregs differentiate into interleukin­17 (IL­17)+Foxp3+ T cells. Our previous study indicated an imbalance of Th17 and Tregs in allergic asthma; however, the underlying mechanisms remain poorly understood. Using quantitative PCR (qPCR), CD39 and CD73 mRNA levels in CD4+ T cells were investigated. Flow cytometry was used to analyze the proportion of IL­17+Foxp3+ T cells, and CD39 and CD73 expressed by CD4+ T cells and Tregs in the peripheral blood of the subjects. The results of the present study demonstrated an increased frequency of CD4+Foxp3+IL­17+ T cells in moderate to severe asthma. A deficiency in CD39 expressed on the surface of CD4+ T cells and Tregs was observed in asthma patients. The expression of CD39 and CD73 on the surface of CD4+ T cells and Tregs was negatively correlated with the number of Th17 cells. These results indicated that the plasticity of Tregs transforming to IL­17+Foxp3+CD4+ T cells, the reduced frequency of CD39+ Tregs and less effective suppression of IL­17 production by residual CD39+ Tregs leads to an imbalance of Th17 and Tregs in asthma. Therefore, enhanced CD39 activity is hypothesized to prevent the progression of asthma.

[Comparison of transient evoked otoacoustic emissions in newborns and adults with frequency specific approach].

OBJECTIVE: To investigate the difference of transient evoked otoacoustic emissions (TEOAE) between neonates and adults with the frequency-specific approach. METHODS: TEOAE were recorded from 112 newborns (62 females, 58 males) who passed hearing screening, and 32 adults (17 females, 15 males) tested with pure-tone threshold equal or less than 20 dBHL. Band reproducibility, signal-to-noise rate (SNR) of frequency-band and half-octave frequency analysis of TEOAE amplitude was recorded respectively. RESULTS: Significant differences were found in two groups, the higher entire TEOAE level found in newborn [(15.18 +/- 4.39) dB SPL] was higher than that of adults group [(9.51 +/- 4.12) dB SPL, P < 0.05]. The lowest wave reproducibility and SNR were in first frequency band (0.8 kHz) for neonate, and then, in last frequency band (4.0 kHz) were for young adults. For newborns, the highest band reproducibility and SNR were presented at fourth frequency band (3.2 kHz). However, for adults, the highest band reproducibility and SNR were presented at second frequency band (1.5 kHz). Frequency space of the SNR response peaks between neonates and adults was 1.7 kHz. The level difference was 7.09 dB SPL. Half octave frequency analysis shows a TEOAE response peaks in neonates was (10.50 +/- 5.09) dB SPL at the 2828 Hz, and in adults, it was (2.84 +/- 5.33) dB SPL at the 1414 Hz. Frequency space of the TEOAE response peaks between neonates and adults was 1414 Hz. Level differences of TEOAE response peaks was 7.66 dB SPL. TEOAE response peak in adult appear at 1.5 kHz, and then dropped down correlated to increase of frequency. From the first to the last testing frequency band, the difference of TEOAE level between neonate and adult was found to increase correlated to increase of frequency. CONCLUSIONS: TEOAE response level in newborn is higher than that in adult group. Further, the decrease of TEOAE response level presented more sharpens with the frequency increasing in adult. The frequency of TEOAE response peak in neonate (3.2 kHz) is higher than adult (1.5 kHz). The level of TEOAE response peak is also greater than adult.

Frequency distribution of synchronized spontaneous otoacoustic emissions showing sex-dependent differences and asymmetry between ears in 2- to 4-day-old neonates.

OBJECTIVE: The mature pattern of frequency distribution of synchronized spontaneous otoacoustic emissions (SSOAEs) has been reported to be bimodal in adults and children between 5 and 11 years of age; however, little is known about the distribution in neonates between 2 and 4 days after birth. Furthermore, overall differences in frequency distribution resulting from difference in sex and asymmetry between ears have not been carefully examined. The aim of this study is to determine the frequency distribution of SSOAEs in neonates at 2 to 4 days of age, evaluate the maturity of the pattern of distribution in this age group, and to evaluate the effects of differences in sex and asymmetry between left and right ears on the frequency distribution. METHODS: We evaluated 224 ears in 112 newborns (59 girls, 53 boys) whose ages ranged from 2 to 4 days. The SSOAEs were measured using ILO96. RESULTS: Most of the SSOAEs (86.5%) appeared at frequencies between 1.01 and 4.50 kHz. The overall frequency distribution of the SSOAEs showed a 'peak-valley-peak' pattern when plotted. Two peaks with maxima at 1.41-1.60 and 3.01-3.20 kHz were separated by a valley with a minimum at 2.41-2.60 kHz. Both girls and boys had approximate monomodal patterns in the distribution of SSOAEs. Significant sex-dependent differences were noted with more SSOAEs at the lower frequencies (