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.

[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].

Delivering umbilical cord mesenchymal stem cell exosomes through hydrogel ameliorates vaginal atrophy in ovariectomized rats.

BACKGROUND: Menopausal and postmenopausal women often experience vaginal atrophy due to estrogen deficiency. Mesenchymal stem cell exosomes have emerged as potential therapeutic agents, capable of promoting tissue regeneration and repair. OBJECTIVE: This study aimed to explore the benefits of exosomes on VK2 cells and the therapeutic effect of topical exosomal hydrogel on atrophic vaginas. METHODS: Exosomes were extracted using the high-speed centrifugation method, and their effects on VK2 cell proliferation, migration, and differentiation were observed through co-culture. The menopause model was induced by ovariectomy in rats, followed by the injection of exosome-loaded hydrogel into their vaginas. The treatment's effectiveness was evaluated by measuring vaginal epithelium thickness using HE staining, and assessing vaginal mucosa proliferation and lamina propria angiogenesis using Ki67 and anti-CD31 staining, respectively. RESULTS: Exosomes significantly promoted VK2 cell proliferation and migration, but had no significant effect on differentiation. The exosome hydrogel increased the expression of Ki67 and CD31, leading to a significant improvement in epithelial thickness. CONCLUSIONS: UcMSC- ex can stimulate the proliferation and migration of VK2 cells, but do not appear to promote differentiation. Topical application of exosome hydrogel enhances vaginal epithelium thickness to a certain degree, offering a promising non-hormonal therapeutic strategy to alleviate vaginal atrophy in postmenopausal women.

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.

Clinical efficacy of tetrandrine in artificial stone-associated silicosis: A retrospective cohort study.

Background: Outbreaks of silicosis have occurred among workers in the artificial stone (AS) industry, and there is currently no effective antifibrosis treatment for silicosis. Design: A retrospective cohort study. Methods: We retrospectively analyzed the clinical data of 89 artificial stone-associated silicosis patients treated in Shanghai Pulmonary Hospital (China). Patients who agreed to be administered tetrandrine entered the observation group and those who disagreed entered the control group. Changes in chest HRCT, pulmonary function, and clinical symptoms of patients in two groups were compared pre- and post-treatment. Results: After treatment for 3-12 months, 56.5%-65.4% of patients in the observation group showed improvements in HRCT imaging, while there was no improvement in the control group (p < 0.05). Disease progression occurred in 0%-17.4% of patients in the observation group after 3-12 months of treatment compared with 44.4%-92.0% of patients in the control group (p < 0.05). After 3 months of treatment, the forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and diffusing capacity of the lung for carbon monoxide (DLco) in the observation group increased by 136.7 ± 189.2 mL (p < 0.05), 124.2 ± 169.9 mL (p < 0.05), and 1.4 ± 2.3 mL/min/mmHg (p > 0.05), respectively, while those in the control group decreased (145.8 ± 356.5; 107.5 ± 272.1; 1.9 ± 3.8). After 6 months of treatment, FVC, FEV1, and DLco in the observation group increased by 207.8 ± 372.2 mL (p > 0.05), 107.8 ± 295.2 mL (p > 0.05) and 0.7 ± 6.0 mL/min/mmHg (p > 0.05), respectively, while those of the control group decreased (383.3 ± 536.7; 215.6 ± 228.9; 1.4 ± 1.7). The incidences of clinical symptoms such as cough, expectoration, dyspnea, chest tightness, and chest pain in the observation group were decreased-after treatment (all p < 0.05), while the incidences of these symptoms increased in the control group, although the change was not statistically significant (all p > 0.05). Conclusion: Tetrandrine can control and delay the progression of AS-associated silicosis fibrosis, with improved chest HRCT imaging and pulmonary function.

Nsun2 coupling with RoRγt shapes the fate of Th17 cells and promotes colitis.

T helper 17 (Th17) cells are a subset of CD4+ T helper cells involved in the inflammatory response in autoimmunity. Th17 cells secrete Th17 specific cytokines, such as IL-17A and IL17-F, which are governed by the master transcription factor RoRγt. However, the epigenetic mechanism regulating Th17 cell function is still not fully understood. Here, we reveal that deletion of RNA 5-methylcytosine (m5C) methyltransferase Nsun2 in mouse CD4+ T cells specifically inhibits Th17 cell differentiation and alleviates Th17 cell-induced colitis pathogenesis. Mechanistically, RoRγt can recruit Nsun2 to chromatin regions of their targets, including Il17a and Il17f, leading to the transcription-coupled m5C formation and consequently enhanced mRNA stability. Our study demonstrates a m5C mediated cell intrinsic function in Th17 cells and suggests Nsun2 as a potential therapeutic target for autoimmune disease.

The relationship between pelvic floor functions and vaginal microbiota in 6-8 weeks postpartum women.

The impairment of pelvic floor muscle functions and Lactobacillus-deficient vaginal microbiota is common in postpartum women. However, few studies have explored the correlation between pelvic floor muscle functions and vaginal microbiota. Given this research gap, our study aims to investigate any potential association between these two conditions of postpartum women (6-8 weeks after childbirth). A total of 230 women who required postpartum pelvic floor function examination at Peking University International Hospital from December 2021 to April 2022 were enrolled in this study. The collected questionnaire information included progestational weight, body mass index (BMI), weight gain during pregnancy, neonatal weight, delivery type, multiparity, postpartum time, and urinary incontinence (UI). A total of 187 samples of vaginal secretions were collected, and the vaginal microbiota was detected by 16S rRNA sequence analysis. Finally, 183 samples were analyzed in the trial. All individuals were divided into two groups according to the results of pelvic floor muscle assessment to explore the difference between the incidence of postpartum urinary incontinence and vaginal microbiota. We found that the prevalence of UI was higher in the group with weakened pelvic floor muscles. Vaginal delivery, overweight, age, neonatal weight, and weight gain during pregnancy were all risk factors for postpartum urinary incontinence. The vaginal microbiome was no longer Lactobacillus dominant of most postpartum women (91.8%), while the diversity of microbiota increased. The Lactobacillus-deficient community, commonly labeled as community state type (CST) IV, was sub-divided into four communities. The abundance of vaginal Lactobacillus decreased in the group with compromised pelvic muscle functions, while the species richness and diversity increased significantly. In conclusion, the decreased pelvic floor muscle functions of postpartum women 6-8 weeks after delivery may disrupt the balance of vaginal microbiota, and the restoration of pelvic floor functions may contribute to a healthy and balanced vaginal microbiota.

The impact of pelvic floor electrical stimulation on vaginal microbiota and immunity.

Pelvic floor electrical stimulation (ES) is an effective treatment for pelvic floor dysfunction. However, the impact of ES on vaginal microbiota and local inflammatory response is yet poorly understood. Therefore, we designed a longitudinal study to investigate the impact of ES on vaginal microbiota and cytokines. A total of 170 participants were recruited into the study at Peking University International Hospital, Beijing, China, from December 2021 to April 2022. They were divided into two groups concerning the follow-up: long-term cohort (n = 147) following up to seven treatment sessions and short-term cohort (n = 23) following up to 7 h after a 30-min treatment. Paired vaginal discharge samples were collected from 134 individuals. Vaginal microbiota was characterized by 16S rRNA sequencing, and local cytokines concentrations were detected by the cytometric bead array method. A significant increase in the relative abundance of Lactobacillus spp. was observed after ES treatment (P < 0.001). In addition, L. crispatus (P = 0.012) and L. gasseri (P = 0.011) also increased significantly. Reduced microbial diversity was observed in the vaginal microbiota after the treatment. In the long-term cohort, a significant downregulation of IFN-γ, IL-2, IL-4, IL-10, IL-17A, and TNF-α was compared with baseline. However, the short-term cohort presented with an elevated IL-6 level at 7 h after the treatment. In conclusion, this study suggested that transvaginal electrical stimulation might help to restore and maintain a healthy vaginal microbiota dominated by Lactobacillus, reducing the risk of vaginal inflammation.

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.

Risk Factors of Silicosis Progression: A Retrospective Cohort Study in China.

Background: Silicosis poses a threat to workers' health due to the irreversible lung lesions. Design: A retrospective cohort study. Methods: A total of 259 patients [80 worked with artificial stone (AS), 179 with non-artificial stone (non-AS)] with confirmed silicosis were included in this study. Forty-one of AS and 91 of non-AS had approximately 2 years' follow-up records [lung function tests and high-resolution computer tomography (HRCT)]. Compared with the first records, increased, densified, or newly emerging lesions in lung HRCT images were judged as progression of the disease. Cox proportional hazards models were used to determine the risk factors. Kaplan-Meier survival curve and log-rank test were used to compare prognostic factors for cumulative risk of progression. Results: In 132 patients with median follow-up of 24.0 months (IQR, 13.8, 24.9), 66 patients showed progression, in them, 36 (87.8%) were from AS group and 30 (32.9%) from non-AS group. Working experience of AS processing (hazard ratio, 5.671; 95% CI, 3.048-10.550) and complicated silicosis in CT images (hazard ratio, 2.373; 95% CI, 1.379-4.082) were the main risk factors associated with progression. Forced vital capacity decreased after 1-year (241.5 vs. 55.2 mL) and 2-year (328.1 vs. 68.8 mL) follow-up in the two groups (AS vs. non-AS). History of anti-tuberculosis medication, chest oppression and pain, ground-glass opacity, pleural abnormalities, and restrictive pulmonary dysfunction were more frequently found on HRCT images in the AS group than non-AS group. Lung functions (DLCO, %) were lower in the current/former smokers than the non-smokers (P < 0.05) in AS patients. Conclusion: Prevention and protection rules are needed to be enforced in the occupation involving AS processing; smoking may be associated with declined lung function in AS patients.

Enhanced fluoride removal from water by nanosized cerium oxides impregnated porous polystyrene anion exchanger.

Efficient elimination of fluoride from wastewater is an urgent need for ensuring water safety. In the present study, a stable and reusable nanocomposite (NCO@PAE) was synthesized by impregnating nanosized cerium oxides (NCO) inside a porous polystyrene anion exchanger (PAE) host for efficient fluoride removal from wastewater. The newly fabricated NCO@PAE exhibited excellent resistance to acid and alkali environment, allowing it to be utilized in a wide pH range (2-12). Fluoride uptake onto NCO@PAE was a pH-dependent process, which could reach the maximum capacity at pH 3.0. Compared with its host PAE, NCO@PAE showed conspicuous adsorption affinity towards fluoride in the coexistence of other competing anions at high concentrations. Adsorption kinetics confirmed its high efficiency for achieving equilibrium within 120 min. Fixed-bed adsorption runs demonstrated that the effective processing capacity of NCO@PAE for synthetic fluoride-containing wastewater (initial fluoride 2.5 mg/L) was about ~330 BV (bed volume), while only 22 BV for the host PAE. The exhausted NCO@PAE could be effectively revived by a simple in-situ desorption method for long-term cycle operation without conspicuous capacity loss. All the results indicated that NCO@PAE is a reliable and promising adsorbent for water defluoridation.

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.

Deciphering the mechanism of medium size anammox granular sludge driving better nitrogen removal performance.

In this study, an integrated investigation to the microbial activities, extracellular polymeric substance (EPS), microbial community and function of anammox granular sludge (AnGS) was performed.Results showed that AnGS at 0.5-1.0 mm had the highest average specific anammox activity (SAA) of 345.9 mg NH4+-N·gVSS-1·d-1, but AnGS at 1.0-1.5 mm with higher SAA might lead to better nitrogen removal efficiency. The content of slime EPS and SAA achieved positively correlation with R2 of 98.11%, while protein/polysaccharide ratio of slime EPS and sludge volume index achieved negatively correlation with R2 of 99.13%. Cadidatus Broccadia and Denitratisoma were positive correlations and most abundant in AnGS 0.5-1.0 mm of 20% and AnGS 1.0-1.5 mm of 37%, respectively. AnGS at 0.5-1.0 mm exhibited higher energy metabolism which mostly contributed to produce protein. The study provides new insights into the mechanisms of AnGS about 1 mm playing more important role in nitrogen removal performance.

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.

Dynamic transcriptomic m5 C and its regulatory role in RNA processing.

RNA 5-methylcytosine (m5 C) is a prevalent RNA modification in multiple RNA species, including messenger RNAs (mRNAs), transfer RNAs (tRNAs), ribosomal RNAs (rRNAs), and noncoding RNAs (ncRNAs), and broadly distributed from archaea, prokaryotes to eukaryotes. The multiple detecting techniques of m5 C have been developed, such as m5 C-RIP-seq, miCLIP-seq, AZA-IP-seq, RNA-BisSeq, TAWO-seq, and Nanopore sequencing. These high-throughput techniques, combined with corresponding analysis pipeline, provide a precise m5 C landscape contributing to the deciphering of its biological functions. The m5 C modification is distributed along with mRNA and enriched around 5'UTR and 3'UTR, and conserved in tRNAs and rRNAs. It is dynamically regulated by its related enzymes, including methyltransferases (NSUN, DNMT, and TRDMT family members), demethylases (TET families and ALKBH1), and binding proteins (ALYREF and YBX1). So far, accumulative studies have revealed that m5 C participates in a variety of RNA metabolism, including mRNA export, RNA stability, and translation. Depletion of m5 C modification in the organism could cause dysfunction of mitochondria, drawback of stress response, frustration of gametogenesis and embryogenesis, abnormality of neuro and brain development, and has been implicated in cell migration and tumorigenesis. In this review, we provide a comprehensive summary of dynamic regulatory elements of RNA m5 C, including methyltransferases (writers), demethylases (erasers), and binding proteins (readers). We also summarized the related detecting technologies and biological functions of the RNA 5-methylcytosine, and provided future perspectives in m5 C research. This article is categorized under: RNA Processing > RNA Editing and Modification.

Diagnostic value of volumetric capnography in patients with chronic cough variant asthma.

OBJECTIVES: To evaluate the quantitative changes and diagnostic performance of volumetric capnography (VCap) parameters in patients with cough variant asthma. METHODS: This cross-sectional study enrolled 31 patients with cough variant asthma and 30 patients with chronic cough without asthma between November 2010 and March 2012. VCap measurements were recorded at baseline, during the five steps of the histamine challenge, and after bronchodilation with salbutamol. They were then compared between the baseline and histamine challenge, and between the two groups. Receiver operating characteristic curve analysis was performed for different VCap measurements. RESULTS: The slope of phase III (dc\dv3) and the ratio of phase III slope to phase II slope (SR23%) decreased from baseline upon challenge with 1.1 mg histamine in cough variant asthma patients but increased in patients with chronic cough without asthma. Additionally, the change upon challenge with 1.1 mg histamine in dc\dv3 from baseline (S6-S1dc\dv3) in cough variant asthma patients had the largest area under the curve (AUC) (0.814, 95% CI: 0.697-0.931; p<0.001). The AUC for change upon challenge with 1.1 mg histamine in SR23% from baseline was 0.755 (95%CI: 0.632-0.878; p<0.001). At a cutoff of 19.8, S6-S1 dc\dv3 had a sensitivity of 74.2% and specificity of 90.0% and at a cutoff of 40.7, S6-S1 SR23% had a sensitivity of 48.4% and specificity of 96.7%. CONCLUSION: Patients with cough variant asthma exhibit distinct VCap responses for dead space parameters upon challenge with histamine in comparison to patients with chronic cough. VCap parameters like phase III slope and phase III/phase II slope ratio could be used to aid the diagnosis of cough variant asthma.

Epitranscriptomic 5-Methylcytosine Profile in PM2.5-induced Mouse Pulmonary Fibrosis.

Exposure of airborne particulate matter (PM) with an aerodynamic diameter less than 2.5 µm (PM2.5) is epidemiologically associated with lung dysfunction and respiratory symptoms, including pulmonary fibrosis. However, whether epigenetic mechanisms are involved in PM2.5-induced pulmonary fibrosis is currently poorly understood. Herein, using a PM2.5-induced pulmonary fibrosis mouse model, we found that PM2.5 exposure leads to aberrant mRNA 5-methylcytosine (m5C) gain and loss in fibrotic lung tissues. Moreover, we showed the m5C-mediated regulatory map of gene functions in pulmonary fibrosis after PM2.5 exposure. Several genes act as m5C gain-upregulated factors, probably critical for the development of PM2.5-induced fibrosis in mouse lungs. These genes, including Lcn2, Mmp9, Chi3l1, Adipoq, Atp5j2, Atp5l, Atpif1, Ndufb6, Fgr, Slc11a1, and Tyrobp, are highly related to oxidative stress response, inflammatory responses, and immune system processes. Our study illustrates the first epitranscriptomic RNA m5C profile in PM2.5-induced pulmonary fibrosis and will be valuable in identifying biomarkers for PM2.5 exposure-related lung pathogenesis with translational potential.

Exercise Capacity and Ventilatory Efficiency in Patients With Pulmonary Embolism After Short Duration of Anticoagulation Therapy.

BACKGROUND: Although anticoagulation therapy can reduce the risk for pulmonary embolism (PE) recurrence, symptoms such as exertional dyspnea or pain can persist for several months to years. Therefore, we aimed to assess the improvement of ventilatory efficiency and exercise capacity during cardiopulmonary exercise test in PE patients after short duration of anticoagulant therapy. MATERIALS AND METHODS: Pulmonary function testing, arterial blood gas analysis and cardiopulmonary exercise test were performed in 30 PE patients after anticoagulant therapy of 4 weeks (early phase) and after 6 months (late phase). In addition, another 30 healthy volunteers underwent the same tests. RESULTS: Percentage of forced vital capacity (FVC %pred) improvement was evident in the PE group (P < 0.01) after 6 months of treatment. Peak Load, peak Load %pred, peak oxygen uptake (V∘O2), peak V∘O2%pred increased significantly after treatment for 6 months (P < 0.01), while lowest minute ventilation in relation to carbon dioxide production (V∘E / V∘CO2) and lowest V∘E / V∘CO2 %pred decreased significantly (P = 0.001). In PE group, the increment of peak V∘O2 %pred from 4 weeks to 6 months correlated with the decrease of lowest V∘E / V∘CO2 %pred (r = 0.639, P < 0.001) but not the increment of FVC %pred (r = 0.058, P = 0.769). CONCLUSIONS: Exercise capacity improved significantly and there was a gradual improvement in ventilatory efficiency after 6 months of anticoagulation therapy.

Diagnostic value of volumetric capnography in patients with chronic cough variant asthma

OBJECTIVES: To evaluate the quantitative changes and diagnostic performance of volumetric capnography (VCap) parameters in patients with cough variant asthma. METHODS: This cross-sectional study enrolled 31 patients with cough variant asthma and 30 patients with chronic cough without asthma between November 2010 and March 2012. VCap measurements were recorded at baseline, during the five steps of the histamine challenge, and after bronchodilation with salbutamol. They were then compared between the baseline and histamine challenge, and between the two groups. Receiver operating characteristic curve analysis was performed for different VCap measurements. RESULTS: The slope of phase III (dc/dv3) and the ratio of phase III slope to phase II slope (SR23%) decreased from baseline upon challenge with 1.1 mg histamine in cough variant asthma patients but increased in patients with chronic cough without asthma. Additionally, the change upon challenge with 1.1 mg histamine in dc/dv3 from baseline (S6-S1dc/dv3) in cough variant asthma patients had the largest area under the curve (AUC) (0.814, 95% CI: 0.697-0.931; p<0.001). The AUC for change upon challenge with 1.1 mg histamine in SR23% from baseline was 0.755 (95%CI: 0.632-0.878; p<0.001). At a cutoff of 19.8, S6-S1 dc/dv3 had a sensitivity of 74.2% and specificity of 90.0% and at a cutoff of 40.7, S6-S1 SR23% had a sensitivity of 48.4% and specificity of 96.7%. CONCLUSION: Patients with cough variant asthma exhibit distinct VCap responses for dead space parameters upon challenge with histamine in comparison to patients with chronic cough. VCap parameters like phase III slope and phase III/phase II slope ratio could be used to aid the diagnosis of cough variant asthma.