RNA 5-Methylcytosine Facilitates the Maternal-to-Zygotic Transition by Preventing Maternal mRNA Decay.

The maternal-to-zygotic transition (MZT) is a conserved and fundamental process during which the maternal environment is converted to an environment of embryonic-driven development through dramatic reprogramming. However, how maternally supplied transcripts are dynamically regulated during MZT remains largely unknown. Herein, through genome-wide profiling of RNA 5-methylcytosine (m5C) modification in zebrafish early embryos, we found that m5C-modified maternal mRNAs display higher stability than non-m5C-modified mRNAs during MZT. We discovered that Y-box binding protein 1 (Ybx1) preferentially recognizes m5C-modified mRNAs through π-π interactions with a key residue, Trp45, in Ybx1's cold shock domain (CSD), which plays essential roles in maternal mRNA stability and early embryogenesis of zebrafish. Together with the mRNA stabilizer Pabpc1a, Ybx1 promotes the stability of its target mRNAs in an m5C-dependent manner. Our study demonstrates an unexpected mechanism of RNA m5C-regulated maternal mRNA stabilization during zebrafish MZT, highlighting the critical role of m5C mRNA modification in early development.

Long-term and multiscale assessment of methanogenesis enhancement mechanisms in magnetite nanoparticle-mediated anaerobic digestion reactor.

Magnetite nanoparticles (Fe3O4-NPs) have been demonstrated to be involved in direct interspecies electron transfer between syntrophic bacteria, yet a comprehensive assessment of the ability of Fe3O4-NPs to cope with process instability and volatile fatty acids (VFAs) accumulation in scaled-up anaerobic reactors is still lacking. Here, we investigated the start-up characteristics of an expanded granular sludge bed (EGSB) with Fe3O4-NPs as an adjuvant at high organic loading rate (OLR). The results showed that the methane production rate of R1 (with Fe3O4-NPs) was approximately 1.65 folds of R0 (control), and effluent COD removal efficiency was maintained at approximately 98.32% upon 20 kg COD/(m3·d) OLR. The components of volatile fatty acids are acetate and propionate, and the rapid scavenging of propionate accumulation was the difference between R1 and the control. The INT-ETS activity of R1 was consistently higher than that of R0 and R2, and the electron transfer efficiencies increased by 68.78% and 131.44%, respectively. Meanwhile, the CV curve analysis showed that the current of R1 was 40% higher than R3 (temporary addition of Fe3O4-NPs), indicating that multiple electron transfer modes might coexist. High-throughput analysis further revealed that it was difficult to reverse the progressive deterioration of system performance with increasing OLR by simply reconfiguring bacterial community structure and abundance, demonstrating that the Fe3O4-NPs-mediated DIET pathway is a prerequisite for establishing multiple electron transfer systems. This study provides a long-term and multi-scale assessment of the gaining effect of Fe3O4-NPs in anaerobic digestion scale-up devices, and provides technical support for their practical engineering applications.

Fractional exhaled nitric oxide in idiopathic pulmonary arterial hypertension and mixed connective tissue disease complicating pulmonary hypertension.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) has been extensively studied in various causes of pulmonary hypertension (PH), but its utility as a noninvasive marker remains highly debated. The objective of our study was to assess FeNO levels in patients with idiopathic pulmonary arterial hypertension (IPAH) and mixed connective tissue disease complicating pulmonary hypertension (MCTD-PH), and to correlate them with respiratory functional data, disease severity, and cardiopulmonary function. METHODS: We collected data from 54 patients diagnosed with IPAH and 78 patients diagnosed with MCTD-PH at the Shanghai Pulmonary Hospital Affiliated to Tongji University. Our data collection included measurements of brain natriuretic peptide (pro-BNP), cardiopulmonary exercise test (CPET), pulmonary function test (PFT), impulse oscillometry (IOS), and FeNO levels. Additionally, we assessed World Health Organization functional class (WHO-FC) of each patient. RESULTS: (1) The fractional exhaled concentration of nitric oxide was notably higher in patients with IPAH compared to those with MCTD-PH. Furthermore, within the IPAH group, FeNO levels were found to be lower in cases of severe IPAH compared to mild IPAH (P = 0.024); (2) In severe pulmonary hypertension as per the WHO-FC classification, FeNO levels in IPAH exhibited negative correlations with FEV1/FVC (Forced Expiratory Velocity at one second /Forced Vital Capacity), MEF50% (Maximum Expiratory Flow at 50%), MEF25%, and MMEF75/25% (Maximum Mid-expiratory Flow between 75% and 25%), while in severe MCTD-PH, FeNO levels were negatively correlated with R20% (Resistance at 20 Hz); (3) ROC (Receiving operator characteristic curve) analysis indicated that the optimal cutoff value of FeNO for diagnosing severe IPAH was 23ppb; (4) While FeNO levels tend to be negatively correlated with peakPETO2(peak end-tidal partial pressure for oxygen) in severe IPAH, in mild IPAH they had a positive correlation to peakO2/Heart rate (HR). An interesting find was observed in cases of severe MCTD-PH, where FeNO levels were negatively correlated with HR and respiratory exchange ratio (RER), while positively correlated with O2/HR throughout the cardiopulmonary exercise test. CONCLUSION: FeNO levels serve as a non-invasive measure of IPAH severity. Although FeNO levels may not assess the severity of MCTD-PH, their significant makes them a valuable tool when assessing severe MCTD-PH.

Effect of Vitamin D on the Proliferation and Barrier of Atrophic Vaginal Epithelial Cells.

Atrophic vaginitis is very common in postmenopausal women due to declining estrogen levels. Vitamin D plays an important role in promoting epithelial cell proliferation, migration and adhesion. We established a rat model of ovariectomy (OVX) induced atrophic vaginitis with the aim of investigating the effects of Vitamin D supplementation on the vaginal epithelial barrier. The results showed that ovariectomised rats had significantly higher vaginal pH, reduced Lactobacillus, significantly lower uterine and vaginal weights, and lower vaginal epithelial PCNA, occludin, and E-cadherin mRNA expression compared with sham-operated rats. Vitamin D supplementation could reduce the vaginal pH, promote the proliferation and keratinization of vaginal epithelial cells, enhance the expression of PCNA mRNA in vaginal tissues, and improve the vaginal and uterine atrophy. Vitamin D can also increase the expression of E-cadherin and occludin proteins in vaginal tissues, maintain the integrity of the vaginal epithelium, increase the number of Lactobacillus, and reduce pathogenic bacterial infections. In vitro experiments demonstrated that 1,25(OH)2D3 could promote the proliferation and migration of VK2/E6E7 vaginal epithelial cells and increase the expression of E-cadherin protein. In conclusion, we demonstrated that Vitamin D can regulate the expression of vaginal epithelial tight junction proteins, promotes cell proliferation, and improves vaginal atrophy due to estrogen deficiency.

Long-term variability of impulse oscillometry and spirometry in stable COPD and asthma.

BACKGROUND: While optimizing spirometry is a challenge for lung function labs, long-term variability if any between IOS (impulse oscillometry) parameters and spirometry is not clearly known in stable COPD (chronic obstructive pulmonary disease) and chronic asthma. The forced oscillation technique is increasingly employed in routine lung function testing. Our aim in this study was to determine the variability in oscillometric parameters between clinic visits over weeks or months in two patient groups during a period of clinical stability. Moreover, the research assessed relationships between IOS parameters long-term variability and COPD severity. METHODS: We used data from 73 patients with stable COPD and 119 patients with stable asthma at the Shanghai Pulmonary Hospital Affiliated to Tongji University. Patients were included if they had three or more clinic visits where spirometry and IOS were performed during a clinically stable period. Data recorded from the first three visits were used. The standard deviation (SDbv), the coefficient of variation (COV), intraclass correlation coefficient (ICC) and the coefficient of repeatability (COR) were calculated, Wilcoxon Mann-Whitney test was used for data that did not conform to normality of distributions, Kruskal Wallis test was used to compare with multiple groups, post hoc comparison was analyzed by Bonferroni, Spearman correlation coefficients for non-parametric data, the multiple regression analyses to determine the relationship between long-term variability and airflow obstruction. RESULTS: (1) The repeatability of IOS resistance parameters with ICC values > 0.8 was high in COPD and asthma. ICC values of IOS resistance parameters were higher than IOS reactance parameters; (2) the repeatability of spirometry parameters with ICC values < 0.8 was lower than IOS resistance parameters in different GOLD (the Global Initiative for Chronic Obstructive Lung Disease) stages, the higher the stage the worse the repeatability; (3) the severity of airflow obstruction was correlated with long-term variability of R5 (R at 5 Hz) (P < 0.05) in GOLD4, not with long-term variability of R20 (R at 20 Hz) (P > 0.05) and R5-R20 (P > 0.05). CONCLUSION: IOS resistance parameters have good long-term repeatability in asthma and COPD. Additionally, repeatability of spirometry parameters is lower than IOS resistance parameters in different GOLD stages.

Variation of PetCO2 during incremental exercise and severity of IPAH and CTEPH.

BACKGROUND AND OBJECTIVE: End-tidal PCO2 (PetCO2) patterns during exercise testing as well as ventilatory equivalents for CO2 have been reported for different pulmonary vascular diseases but seldomly for the significant differences in exercise response depending on the etiology of pulmonary hypertension. We aimed to compare PetCO2 change pattern in IPAH and CTEPH with varying severity during incremental cardiopulmonary exercise testing (CPET). METHODS: 164 IPAH patients and 135 CTEPH patients referred to Shanghai Pulmonary Hospital between 2012 and 2019 were retrospectively recruited into the study. All patients performed CPET and also underwent right-heart catheterization (RHC). Forty-four healthy subjects also performed CPET and were included as controls. RESULTS: PetCO2 was significantly lower in IPAH and CTEPH patients as compared to normal subjects. Moreover, the PetCO2 did not rise, in fact fell from rest to anaerobic threshold (AT), then further decreased until peak in both IPAH and CTEPH. PetCO2 value at rest, unloaded, AT and peak were proportionately reduced as the World Health Organization functional class (WHO-Fc) increased in both IPAH and CTEPH patients. The PETCO2 in IPAH patients had significant differences during all phases of exercise between WHO-Fc I-II and III-IV subgroup. CTEPH also demonstrated significant difference except for PetCO2 at peak. PetCO2 values were significantly higher in IPAH during all phases of exercise as compared to CTEPH patients (all P < 0.001). PeakVO2%pred correlated significantly with PetCO2 at rest (r = 0.477, P < 0.001), AT (r = 0.609, P < 0.001) and peak exercise (r = 0.576, P < 0.001) in IPAH. N-terminal natriuretic peptide type-B (NT-proBNP) also correlated markedly with PetCO2, with a correlation coefficient of - 0.326 to - 0.427 (all P < 0.001). Additionally, PetCO2 at rest, at AT and at peak correlated positively with peakVO2%pred and showed an inverse correlation with NT-proBNP in CTEPH patients (all P < 0.05). CONCLUSIONS: PetCO2 during exercise in IPAH and CTEPH patients was significantly different from normal subjects. Moreover, PetCO2 values were significantly higher in IPAH during all phases of exercise as compared to CTEPH patients (all P < 0.001). PetCO2 was progressively more abnormal with increasing disease severity according to peakVO2%pred and WHO-Fc.

Efficacy of Beraprost Sodium Combined with Sildenafil and Its Effects on Vascular Endothelial Function and Inflammation in Patients Experiencing Left Heart Failure Complicated with Pulmonary Arterial Hypertension.

BACKGROUND To explore the efficacy of beraprost sodium combined with sildenafil and its effects on the vascular endothelial function and inflammation in left heart failure patients complicated with pulmonary arterial hypertension. MATERIAL AND METHODS A total of 80 patients with left heart failure complicated with pulmonary arterial hypertension was enrolled as the subjects of this study and assigned into an observation group (n=40) and a control group (n=40) using a random number table. The changes in pulmonary arterial hypertension-associated indicators at 3 months after treatment and the alterations in the levels of cardiac function-associated biochemical indicator brain natriuretic peptide (BNP), inflammatory factor tumor necrosis factor alpha (TNF-alpha), and mean pulmonary arterial pressure during treatment were compared between the 2 groups. RESULTS At 3 months after treatment, the pulmonary arterial hypertension-associated indicators human urotensin II and calcitonin gene-related peptide in the observation group were lower and higher, respectively, than those in control group. Moreover, the observation group had significantly lower BNP and TNF-alpha levels and mean pulmonary arterial pressure than the control group. After intervention, the echocardiographic parameters left ventricular ejection fraction (LVEF), cardiac output (CO), and stroke volume (SV) in both groups were significantly higher than those before intervention, and the observation group had significantly higher LVEF, SV, and CO than the control group after intervention. CONCLUSIONS Beraprost sodium combined with sildenafil for left heart failure complicated with pulmonary arterial hypertension can effectively improve pulmonary arterial hypertension, alleviate left heart failure, and reduce inflammatory responses, thereby achieving better clinical efficacy in patients.

Cardiopulmonary exercise testing and pulmonary function testing for predicting the severity of CTEPH.

BACKGROUND: Cardiopulmonary exercise testing (CPET) and pulmonary function testing (PFT) are noninvasive methods to evaluate the respiratory and circulatory systems. This research aims to evaluate and monitor chronic thromboembolic pulmonary hypertension (CTEPH) noninvasively and effectively by these two methods. Moreover, the research assesses the predictive value of CPET and PFT parameters for severe CTEPH. METHODS: We used data from 86 patients with CTEPH (55 for test set, and 31 for validation set) at the Shanghai Pulmonary Hospital Affiliated to Tongji University. The clinical, PFT and CPET data of CTEPH patients of different severity classified according to pulmonary artery pressure (PAP) (mm Hg) were collected and compared. Logistic regression analysis was performed to appraise the predictive value of each PFT and CPET parameter for severe CTEPH. The performance of CPET parameters for predicting severe CTEPH was determined by receiver operating characteristic (ROC) curves and calibration curves. RESULTS: Data showed that minute ventilation at anaerobic threshold (VE @ AT) (L/min) and oxygen uptake at peak (VO2 @ peak) (mL/kg/min) were independent predictors for severe CTEPH classified according to PAP (mm Hg). Additionally, the efficacy of VE @ AT (L/min) and VO2 @ peak (mL/kg/min) in identifying severe CTEPH was found to be moderate with the area under ROC curve (AUC) of 0.769 and 0.740, respectively. Furthermore, the combination of VE @ AT (L/min) and VO2 @ peak (mL/kg/min) had a moderate utility value in identifying severe CTEPH with the AUC of 0.843. CONCLUSION: Our research suggests that CPET and PFT can noninvasively and effectively evaluate, monitor and predict the severity of CTEPH.

Association of short-term exposure to ambient air pollutants with exhaled nitric oxide in hospitalized patients with respiratory-system diseases.

BACKGROUND: Previous studies have suggested that exposure to ambient air pollutants may adversely affect human health. However, few studies have examined the health effects of exposure to ambient air pollutants in hospitalized patients. OBJECTIVES: To evaluate the association between short-term exposure to ambient air pollutants and exhaled nitric oxide fraction (FeNO) in a large cohort of hospitalized patients. METHODS: FeNO was detected for 2986 hospitalized patients (ages 18-88 years). Daily average concentrations of SO2, NO2, O3, CO, PM2.5 and PM10 in 2014 and 2015 were obtained from nine fixed-site monitoring stations. Multiple linear regression models were chosen to assess the associations of exposure to ambient air pollutants with FeNO while adjusting for confounding variables. Lagged variable models were selected to determine the association between FeNO and ambient air pollutants concentrations with lags of up to 7 days prior to FeNO testing. RESULTS: Interquartile-range (IQR) increases in the daily average SO2 (8.00 µg/m3) and PM2.5 (37.0 µg/m3) were strongly associated with increases in FeNO, with increases of 3.41% [95% confidence interval (CI), 0.94-5.93%] and 2.72% (95%CI, -0.09% to 5.61%), respectively. However, FeNO levels were not statistically associated with PM10, NO2, O3 or CO. In the two-pollutant models, the maximum correlation was for ambient SO2. We also found that FeNO was associated with IQR increases in daily average ambient concentrations of SO2 up to 3 and 4 days after the exposure events. CONCLUSIONS: Short-term exposure to SO2 and PM2.5 were positively correlated with FeNO levels in hospitalized patients in Shanghai.

Self-Immobilization of Car9 Fusion Proteins within High Surface Area Silica Sol-Gels and Dynamic Control of Protein Release.

Protein entrapment within silica matrices during sol-gel formation is an effective way of producing biocatalysts with high load, activity retention, and minimal leaching. On the other hand, mesoporous silica materials have been favored for diffusional control of protein delivery because of their regular pore size and morphology and in spite of the drawback of requiring post-synthesis loading with cargo proteins. Here, we describe a hybrid technology in which fusion of the silica-binding Car9 dodecapeptide to model fluorescent proteins allows for their simultaneous entrapment and surface immobilization within sol-gel monoliths that can be fabricated in air and oil phases. Spherical particles produced by injecting a mixture of silicic acid and Car9-tagged proteins in silicone oil exhibit high surface area (>400 m2/g), 15-nm-diameter mean pore size and homogeneous protein loading. Incubation in arginine-containing buffer disrupts the interaction between Car9 extensions and silica surfaces and triggers the continuous or discontinuous (on/off) release of cargo proteins with pH-tunable kinetics. This simple approach for producing hybrid silica materials that stably encapsulate and release one or more Car9-tagged proteins in a single step may prove useful for applications requiring dynamic control of protein concentration.

Oxygen uptake is more efficient in idiopathic pulmonary arterial hypertension than in chronic thromboembolic pulmonary hypertension.

BACKGROUND AND OBJECTIVE: The responses of oxygen uptake efficiency (OUE) during cardiopulmonary exercise training (CPET) have not been reported in patients with pulmonary hypertension. We aimed to investigate the differences in OUE between patients with idiopathic pulmonary arterial hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Forty-four patients with IPAH and 29 patients with CTEPH were retrospectively enrolled into our study. All patients underwent right-heart catheterization, pulmonary function test and performed the 6-min walk test and CPET. RESULTS: We found that oxygen uptake efficiency plateau (OUEP) and oxygen uptake efficiency at anaerobic threshold (OUE@AT) was significantly higher in IPAH than that in CTEPH (both P = 0.002). However, patients with CTEPH had lower mean pulmonary artery pressure, pulmonary vascular resistance and transpulmonary gradient (all P < 0.05). The correlation between OUEP and heart rate at anaerobic threshold (HR_AT) was significant (r = 0.376, P < 0.05); however, no statistically significant correlation was found with ventilation at anaerobic threshold (VE_AT) (r = -0.074, P > 0.05) in patients with IPAH. In patients with CTEPH, both anaerobic threshold (r = 0.307, P > 0.05) and VE_AT (r = -0.709, P < 0.0001) were reduced. OUEP were higher in WHO functional class I/II patients than in WHO functional class III/IV patients (all P < 0.05). CONCLUSIONS: OUEP and OUE@AT are higher in IPAH than that in CTEPH not in proportion to haemodynamics, probably due to differences in cardiac function and pulmonary vascular occlusion. OUEP correlates well with the exercise capacity and the severity of the disease.

Effect of Radix Stemonae concentrated decoction on the lung tissue pathology and inflammatory mediators in COPD rats.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common and frequently occurring respiratory disease. At present, western medicine treatment of COPD mainly focuses on symptomatic treatment. Using Chinese medicines or integrated Chinese and Western medicines to treat stable COPD has significant efficacy. In this study, we aimed to observe the effect of Radix Stemonae concentrated decoction on the lung tissue pathology and inflammatory mediators in COPD rats and explore its possible mechanism. METHODS: SD rats were randomized into blank group, COPD model group and Radix Stemonae group, 10 cases in each group. Rats were fed for 112 days. Before the rats were sacrificed, lung function of the animals was tested. The right lower lung was fixed for morphologic observation. The inflammatory mediators in serum were determined using enzyme-linked immuno sorbent assay. RESULTS: Body weight of animals in the model group was significantly decreased compared with blank group (P < 0.05). After gavage therapy with Radix Stemonae, body weight was significantly increased (P < 0.05). Compared with the blank group, pulmonary functions of rats in the model group were significantly abnormal (P < 0.05), while in Radix Stemonae group, these indicators turned much better than model group (P < 0.05). As for pathological changes in lungs, airway inflammation in the model group was aggravated. In the Radix Stemonae group, inflammation and emphysema were much milder. The concentrations of TNF-α, IL-8 and LTB4 in both model group and Radix Stemonae group were increased significantly (P < 0.05). But the levels in Radix Stemonae group were decreased significantly than model group (P < 0.05). CONCLUSION: Radix Stemonae concentrated decoction may mitigate and improve airway rebuilding in the lungs of COPD rats by inhibiting the release of inflammatory mediators.

[Correlation between oxygen uptake efficiency and exercise capacity in pulmonary hypertension patients].

OBJECTIVE: To explore the characteristics of oxygen uptake efficiency (OUE) in patients with pulmonary hypertension (PH) and analyze the correlation between OUE and exercise capacity. METHODS: A total of 76 PH patients and 29 healthy controls at Shanghai Pulmonary Hospital between October 2010 and January 2014 were evaluated. All PH patients were classified into 4 groups according to the World Health Organization functional class (WHO-FC). Pulmonary function and cardiopulmonary exercise tests were performed in all subjects. RESULTS: Compared with health control, the PH patients had lower forced vital capacity (FVC) of expected value (%pre), forced expiratory volume in one second (FEV(1))%pre and FEV(1)/FVC ((81.9 ± 15.5)% vs (88.6 ± 14.1)%, (75.0 ± 16.4)% vs (85.2 ± 17.2)% and (78.3 ± 9.3)% vs (88.3 ± 7.3)%, all P < 0.05). Compared with control group, there were also significant reductions in oxygen uptake efficiency slope (OUES), oxygen uptake efficiency plateau (OUEP) and OUE at the anaerobic threshold ((1.14 ± 0.42) vs (2.32 ± 0.34) (L/min)/lg (L/min), (27 ± 5) vs (37 ± 4) ml/L, (24 ± 6) vs (34 ± 5) ml/L, all P < 0.05). No significant differences existed in OUES, OUEP and OUE at the anaerobic threshold in PH patients between WHO-FC Iand WHO-FC II groups. There were significant differences in OUE among other groups (all P < 0.05). And OUES, OUEP and OUE at the anaerobic threshold were correlated positively with exercise tolerance in PH patients. CONCLUSION: OUE significantly declines in PH patients compared with normal subjects and it is correlated positively with exercise capacity.

The ability of volumetric capnography to distinguish between chronic obstructive pulmonary disease patients and normal subjects.

PURPOSE: The aim of our study was to evaluate volumetric capnography (VCap) in the differentiation between chronic obstructive pulmonary disease (COPD) patients and normal subjects. PATIENTS AND METHODS: Thirty-nine healthy male volunteers and 60 male COPD patients were enrolled. Regression equations between VCap indices and age, weight, height, and tidal volume in healthy volunteers were established by stepwise regression analysis. Predicted normal values of VCap indices in COPD patients were calculated. A paired t test was used to compare the difference between observed and predicted values for VCap indices in COPD patients. Receiver operating characteristic (ROC) curve analysis was used to evaluate the power of each VCap index alone in differentiating COPD patients and normal subjects. The power of the combination of VCap indices was assessed by discriminant analysis. RESULTS: All regression equations were significant (P < 0.01) as were the differences between the observed and predicted normal VCap indices in COPD patients (P < 0.001). ROC curve analysis showed that the volume between 25 and 50% of F CO2et (Vm25-50), slope of Phase II (dC2/dV), and slope of Phase III (dC3/dV) were valuable predictors. Nearly all (90.9%) subjects were correctly classified by discriminant analysis. CONCLUSION: Vm25-50, dC2/dV, or dC3/dV alone are valuable for differentiating COPD patients and normal subjects, but more powerful are the combinations of Vm25-50, dC2/dV, and dC3/dV, the ratio of dC2/dV to dC3/dV (SR23), dead space according to the Bohr method (VDB), and dead space according to the Wolff and Brunner methods (PIE).

[Correlation between submaximal exercise measurements and peak oxygen uptake in patients with pulmonary arterial hypertension].

OBJECTIVE: To explore the correlation between submaximal exercise measurements and peak oxygen uptake in patients with pulmonary arterial hypertension (PAH). METHODS: The clinical data were retrospectively analyzed for 106 patients with PAH from Affiliated Shanghai Pulmonary Hospital, Tongji University from October 2010 to October 2013. The examinations included routine pulmonary function test, N-terminal pro-brain natriuretic peptide (NT-proBNP), 6-minute walk test, right heart catheterization and cardiopulmonary exercise testing. And within the same period, matched 20 healthy subjects without smoking and cardiopulmonary diseases were selected as control group. RESULTS: Peak oxygen uptake (P-VO2), anaerobic threshold (AT), oxygen uptake efficiency slope (OUES) and oxygen uptake efficiency plateau (OUEP) were significantly lower in patients with PAH than control group ((841 ± 257) vs (1 682 ± 284) ml/min, (661 ± 171) vs (1 041 ± 243) ml/min, 1.1 ± 0.4 vs 2.3 ± 0.4, 25.8 ± 5.2 vs 35.5 ± 4.0, respectively) (all P < 0.001). And the predicted parametric values (%pred) were also lower in PAH group than control group (all P < 0.001). While the lowest ventilation (VE)/CO2 output (VCO2) (L-VE/VCO2) and VE/VCO2 slope were significantly higher in PAH group than control group (50.5 ± 15.9 vs 30.5 ± 3.0 and 57.2 ± 23.2 vs 25.6 ± 2.8, both P < 0.001). Pearson correlation analysis showed, except for VE/VCO2 slope%pred, AT%pred, L-VE/VCO2%pred, OUES%pred and OUEP%pred were correlated with P-VO2 (all P < 0.001). According to multiple linear regression analysis, only AT%pred and OUES%pred were the independent predictors of P-VO2 (ß = 0.394, 0.384, both P < 0.001) and OUES%pred might be better than AT%pred (the adjusted ß = 0.674). When AT%pred < 58.0% or OUES%pred < 65.0%, exercise capacity in PAH declined obviously with the sensitivity was 92.3% and 96.2% and the specificity 81.2% and 75.5% respectively. CONCLUSIONS: Exercise capacity in patients with PAH is significantly lower than healthy subjects. OUES%pred and AT%pred may be used as an independent predictor of exercise capacity. And OUES%pred may be more powerful.

[Retracted] Activation of the LKB1­SIK1 signaling pathway inhibits the TGF­ß­mediated epithelial­mesenchymal transition and apoptosis resistance of ovarian carcinoma cells.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the Transwell invasion and migration assay data shown in Figs. 2C and 3F were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes, which had either already been published or were under consideration for publication at around the same time. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 17: 2837­2844, 2018; DOI: 10.3892/mmr.2017.8229].

Dynamic RNA methylation modifications and their regulatory role in mammalian development and diseases.

Among over 170 different types of chemical modifications on RNA nucleobases identified so far, RNA methylation is the major type of epitranscriptomic modifications existing on almost all types of RNAs, and has been demonstrated to participate in the entire process of RNA metabolism, including transcription, pre-mRNA alternative splicing and maturation, mRNA nucleus export, mRNA degradation and stabilization, mRNA translation. Attributing to the development of high-throughput detection technologies and the identification of both dynamic regulators and recognition proteins, mechanisms of RNA methylation modification in regulating the normal development of the organism as well as various disease occurrence and developmental abnormalities upon RNA methylation dysregulation have become increasingly clear. Here, we particularly focus on three types of RNA methylations: N6-methylcytosine (m6A), 5-methylcytosine (m5C), and N7-methyladenosine (m7G). We summarize the elements related to their dynamic installment and removal, specific binding proteins, and the development of high-throughput detection technologies. Then, for a comprehensive understanding of their biological significance, we also overview the latest knowledge on the underlying mechanisms and key roles of these three mRNA methylation modifications in gametogenesis, embryonic development, immune system development, as well as disease and tumor progression.

Detection of the airway obstruction stage in asthma using impulse oscillometry system.

OBJECTIVE: Although spirometry is the most common method for evaluating the airway obstruction stage in asthma patients, it is difficult to perform in some patients. The aim of this study was to evaluate whether impulse oscillometry, an easy-to-perform technique, can detect asthmatic airway obstruction stage. METHODS: A total of 80 subjects, including healthy volunteers and patients with asthma, were enrolled in this study. The asthma patients were classified into three groups according to American Thoracic Society (ATS)/European Respiratory Society (ERS)-2005: the mild group (forced expiratory volume in 1 second (FEV(1)) ≥ 70% predicted (Pred), n = 20), the moderate group (50% Pred ≤ FEV(1) <70% Pred, n = 20), and the severe group (FEV(1) < 50% Pred, n = 20). Spirometry and impulse oscillometry (IOS) parameters were obtained from every subject. Correlation analysis was used to compare spirometry measurements and IOS parameters. One-way analysis of variance (ANOVA) was performed to compare IOS parameters among different groups. The potential of using all individual IOS parameters to detect the different stages of asthmatic airway obstruction was evaluated by the receiver operating characteristic (ROC) curve analysis. RESULTS: The correlation analysis showed that IOS parameters, such as respiratory resistance at 5 Hz (R(5)), respiratory resistance at 10 Hz (R(10)), respiratory resistance at 20 Hz (R(20)), difference in resistance between 5 Hz and 20 Hz (R(5-20)), impedance at 5 Hz (Z(5)), resonant frequency (Fres), and area of reactance (AX) were negatively correlated with FEV(1) and peak expiratory flow (PEF), while reactance at 5 Hz (X(5)) was positively correlated with FEV(1) and PEF. The increase in R(5), R(10), R(20), Z(5), R(5-20), Fres, (-X(5)), and AX parameters corresponded significantly with an increase in the airway obstruction stage, as determined by one-way ANOVA . ROC curve analysis revealed that all the IOS parameters studied, except for Fres, were capable of classifying asthmatic airway obstruction. R(5), R(5-20), and Z(5) were the most accurate parameters. CONCLUSION: IOS provides an accurate, reliable, and patient-friendly technique for classifying asthmatic airway obstruction.

[Association of oxygen uptake efficiency in exercise test with exercise capacity in patients with stable chronic obstructive pulmonary disease].

OBJECTIVE: To explore the characteristics of oxygen uptake efficiency (OUE) in patients with chronic obstructive pulmonary disease (COPD), and to analyze the relationship between OUE and the exercise capacity. METHODS: Pulmonary function test and cardiopulmonary exercise test were performed in 59 patients with stable COPD (grade I, n = 15; grade II, n = 16; grade III, n = 19; grade IV, n = 9) and 29 healthy volunteers of the same age. Their successive breathing respiratory exchange parameters were collected and analyzed. t test and χ(2) test were used for 2 sample comparison, while multiple comparisons among groups were performed by using single factor analysis of variance. Correlation analysis was done by Pearson correlation test. RESULTS: Compared with the normal control group [(2.2 ± 0.4) L·min(-1)·lg(L·min(-1))(-1); (35 ± 4) ml/L], the OUES and OUEP of the COPD patient group [(1.9 ± 0.3) L·min(-1)·lg(L·min(-1))(-1); (31 ± 5) ml/L]were significantly lower (t = 4.57, 3.39, all P < 0.01) . The OUE of the grade I patients showed no significant difference compared with the normal control group (t = 0.36-1.49, all P > 0.05), while the OUES of the grade II-IV patients [(2.05 ± 0.26), (1.76 ± 0.28) and (1.63 ± 0.19) L·min(-1)·lg(L·min(-1))(-1)] decreased significantly compared to the normal control group [(2.23 ± 0.39) L·min(-1)·lg(L·min(-1))(-1); t = 2.42-5.26, all P < 0.05]. The OUEP and the OUE at the anaerobic threshold of the grade II-III patients [(31 ± 4) and (31 ± 5), (29 ± 5) and (29 ± 5) ml/L] decreased significantly compared to the normal control group [(35 ± 4) and (34 ± 4) ml/L, t = 2.18-4.83, all P < 0.05]. The OUES, OUEP and the OUE at the anaerobic threshold in COPD patients were correlated (r = 0.500-0.625, all P < 0.01) positively with the exercise tolerance (peak VO2% pred). CONCLUSIONS: The oxygen uptake efficiency of patients with COPD is significantly reduced compared to that of the normal subjects, and is correlated positively with the exercise capacity.

[Effects of whole lung lavage on pulmonary function and exercise capacity in patients with pneumoconiosis].

OBJECTIVE: To investigate the effects of whole lung lavage (WLL) on the pulmonary function and exercise capacity in patients with pneumoconiosis. METHODS: Forty-one patients with pneumoconiosis who quit dust-exposed work not more than 6 months before underwent WLL. Clinical symptom assessment, pulmonary function test, and cardiopulmonary exercise test were performed before and one week after WLL, and the results were compared. RESULTS: The patients with pneumoconiosis showed no significant changes in clinical symptoms after WLL. At one week after WLL, the patients with pneumoconiosis showed nonsignificant increases in forced vital capacity, forced expiratory volume in one second (FEV1.0), and percent predicted FEV1 (P > 0.05); peak oxygen uptake (peak VO2) increased from 2140.6 ± 353.2 ml/min before WLL to 2374.6 ± 362.4 ml/min after WLL, percent predicted peak VO2 increased from 82.2 ± 13.7% before WLL to 91.0 ± 14.0% after WLL, peak VO2/kg increased from 30.6 ± 3.5 ml/min×kg before WLL to 34.2 ± 3.7 ml/min×kg after WLL, and ventilatory equivalent for carbon dioxide decreased from 30.6 ± 3.1 before WLL to 26.1 ± 2.7 after WLL (P < 0.05). CONCLUSION: WLL can remarkably improve the oxygen uptake and ventilatory efficiency in patients with pneumoconiosis during exercise, so it can improve the exercise capacity of these patients.