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Introduction: The presence of emphysema is common in patients with interstitial lung disease (ILD), which is designated as combined pulmonary fibrosis and emphysema (CPFE). This study aimed to examine the association between smoking, emphysema, and fibrosis in ILD patients. Methods: A total of 800 patients hospitalized for ILD at the affiliated hospital of Qingdao University, Shandong, Qingdao, China, from December 2012 to December 2020 were included in our retrospective cohort study. Participants were divided into CPFE and non-CPFE groups. The patients' clinical presentations and radiographic and laboratory findings were reviewed and compared. The two groups were then divided and compared based on smoking status. Kaplan-Meier survival analysis with log-rank testing and multivariable Cox proportional hazards regression analysis were used to compare all-cause mortality. Results: Emphysema was present in 188 (23.5%) ILD patients. Smoking was associated with increased odds of CPFE (adjusted odds ratio, AOR=2.13; 95% CI: 1.33–3.41, p=0.002). The CPFE patients had a comparable risk of death to non- CPFE patients (adjusted hazard ratio, AHR=0.89; 95% CI: 0.64–1.24, p=0.493). Smoking was not a risk prognostic factor in the whole group (AHR=1.34; 95% CI: 0.90–1.99, p=0.152) or the CPFE group (AHR=0.90; 95% CI: 0.43–1.86, p=0.771). However, a significant prognostic difference between smokers and non-smokers was found in the non-CPFE group (AHR=1.62; 95% CI: 1.02–2.58, p=0.042). In ILD patients, smoking pack-years were weakly correlated with total centrilobular emphysema (CLE) scores and total fibrosis scores (TFS), but not with total emphysema scores (TES); TFS were weakly correlated with TES. Conclusions: CPFE did not affect the prognosis of ILD. Smoking was a risk but not a prognostic factor for CPFE. However, smoking was associated with worse survival in non-CPFE patients. There was an intricate association among smoking, emphysema, and fibrosis in ILD patients. [ABSTRACT FROM AUTHOR]

Background: Myeloid-derived suppressor cells (MDSCs) have been reported to expand and have a potent ability in the expansion of regulatory T cells in malignant and infectious disease. The current study was performed to investigate the role of MDSCs and possible immune mechanisms in dampening immune responses of community acquired pneumonia (CAP). Methods: This was a single-center cross-sectional study. The distribution of MDSCs subsets, the PD-1/PD-L1(L2) level of MDSCs subsets and Tregs in the peripheral blood of adult CAP patients and healthy control were measured by flow cytometry analysis. Results: Peripheral blood mononuclear cells (PBMCs) from 63 adult CAP patients contained an elevated frequency of both G-MDSC (4.92±0.30 vs 2.25±0.21,p<0.0001) and M-MDSC (19.40±1.30 vs 9.64±0.57,p<0.001) compared to healthy controls. Treg in the peripheral blood of CAP patients exhibited increased expression of PD-1 and CTLA-4, accompanied by no difference of their frequency. Moreover, up-regulated expression of PD-L1 on MDSC subsets in the peripheral blood of CAP patients was also revealed. Of note, the frequency of circulating MDSCs subset displayed a positive correlation with neutrophil count percentage in blood in CAP patients. Conclusions: In summary, the significant expansion of circulating MDSCs subsets and the up-regulated expression of PD-1/PD-L1 level in CAP patients may suggest the possible involvement of PD-1/PD-L1axis in MDSCs mediated immune regulation on Treg at least partially in CAP patients. [ABSTRACT FROM AUTHOR]

Background: To evaluate the safety and efficacy of daily somatropin (Jintropin®), a recombinant human growth hormone, in prepubertal children with ISS in China. Methods: This study was a multicenter, randomized, controlled, open-label, phase 3 study. All subjects were randomized 3:1 to daily somatropin 0.05 mg/kg/day or no treatment for 52 weeks. A total of 481 subjects with a mean baseline age of 5.8 years were enrolled in the study. The primary endpoint was change in (△) height standard deviation score (HT-SDS) for chronological age (CA). Secondary endpoints included △height from baseline; △bone age (BA)/CA; △height velocity (HV) and △insulin-like growth factor 1 (IGF-1 SDS). Results: △HT-SDS at week 52 was 1.04 ± 0.31 in the treatment group and 0.20 ± 0.33 in the control group (P < 0.001). At week 52, statistical significance was observed in the treatment group compared with control for △height (10.19 ± 1.47 cm vs. 5.85 ± 1.80 cm; P < 0.001), △BA/CA (0.04 ± 0.09 vs. 0.004 ± 0.01; P < 0.001), △HV (5.17 ± 3.70 cm/year vs. 0.75 ± 4.34 cm/year; P < 0.001), and △IGF-1 SDS (2.31 ± 1.20 vs. 0.22 ± 0.98; P < 0.001). The frequencies of treatment-emergent adverse events (TEAEs) were similar for the treatment and the control groups (89.8% vs. 82.4%); most TEAEs were mild to moderate in severity and 23 AEs were considered study-drug related. Conclusions: Daily subcutaneous administration of somatropin at 0.05 mg/kg/day for 52 weeks demonstrated improvement in growth outcomes and was well tolerated with a favorable safety profile. Trial Registration: ClinicalTrials.gov (identifier: NCT03635580). URL: https://clinicaltrials.gov/ct2/show/NCT03635580 [ABSTRACT FROM AUTHOR]

Background: Myeloid-derived suppressor cells (MDSCs) have crucial immunosuppressive role in T cell dysfunction in various disease processes. However, the role of MDSCs and their impact on Tregs in COPD have not been fully understood. The aim of the present study is to investigate the immunomodulatory role of MDSCs and their potential impact on the expansion and function of Tregs in COPD patients., Methods: Peripheral blood samples were collected to analyze circulating MDSCs, Tregs, PD-1/PD-L1 expression to assess the immunomodulatory role of MDSC and their potential impact on the expansion and function of Treg in COPD. A total of 54 COPD patients and 24 healthy individuals were enrolled in our study. Flow cytometric analyses were performed to identify granulocytic MDSCs (G-MDSCs), monocytic MDSCs (M-MDSCs), Tregs, and the expression of PD-1/PD-L1(L2) on MDSCs and Tregs in peripheral blood., Results: Our results revealed a significantly higher percentage of G-MDSCs and M-MDSCs ( p < 0.001) in COPD patients compared to the healthy controls. Additionally, a significantly higher proportion of peripheral blood Tregs was observed in COPD patients. Furthermore, an increased expression of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) on Tregs ( p < 0.01) was detected in COPD patients. The expression of PD-1 on CD4 + Tcells and Tregs, but not CD8 + Tcells, was found to be increased in patients with COPD compared to controls. Furthermore, an elevated expression of PD-L1 on M-MDSCs ( p < 0.01) was also observed in COPD patients. A positive correlation was observed between the accumulation of M-MDSCs and Tregs in COPD patients. Additionally, the percentage of circulating M-MDSCs is positively associated with the level of PD-1 (r = 0.51, p < 0.0001) and CTLA-4 (r = 0.42, p = 0.0014) on Tregs in COPD., Conclusion: The recruitment of MDSCs, accumulation of Tregs, and up-regulation of CTLA-4 on Treg in COPD, accompanied by an increased level of PD-1/PD-L1, suggest PD-1/PD-L1 axis may be potentially involved in MDSCs-induced the expansion and activation of Treg at least partially in COPD., Competing Interests: The authors declare that they have no competing interests., (© 2024 Zhang et al.)

Objectives: To investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of Y-shape branched PEGylated recombinant human growth hormone (YPEG-rhGH) and evaluate its short-term efficacy and safety in children with growth hormone deficiency (GHD)., Methods: A total of 43 children with GHD from 12 sites in China were enrolled in this randomized, multicenter, active-controlled, double-blind (YPEG-rhGH doses) trial. Patients were randomized 1:1:1:1 to 100, 120, and 140 μg/kg/week of YPEG-rhGH groups and daily rhGH 35 μg/kg/day groups. The treatment lasted 12 weeks. The primary outcome was the area under the curve of the change of insulin-like growth factor-1 (IGF-1). The secondary outcome was the height velocity (HV) increment at week 12., Results: A dose-dependent response of maximum plasma concentration (C max ) and area under the concentration-time curves from 0 to 168 hours (AUC 0-168h ) were observed for YPEG-rhGH. The ratio of C max and the ratio of AUC 0-168h from the first to the last dosing were 1.09~1.11 and 1.22~1.26 respectively. A YPEG-rhGH dose-dependent increase in area under effect curve (AUEC) of IGF-1 fold change was observed. Model-derived mean IGF-1 SDS was in the normal range for all three YPEG-rhGH doses. At week 12, HV was 7.07, 10.39, 12.27 cm/year, and 11.58 cm/year for YPEG-rhGH 100, 120, and 140 μg/kg/week and daily rhGH respectively. Adherence and safety were consistent with the profile of daily rhGH. No related serious adverse events were reported., Conclusion: The PK/PD suggests that YPEG-rhGH is suitable for the once-weekly treatment of pediatric GHD. YPEG-rhGH 120 ~ 140 μg/kg/week provides the closest HV increment with similar safety and tolerability compared to daily rhGH 35 μg/kg/day in children with GHD., Clinical Trial Registration: ClinicalTrials.gov, identifier [NCT04513171]., Competing Interests: LS is the president of Xiamen Amoytop Biotech Co., Ltd. RH and WZ are employees of Xiamen Amoytop Biotech Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liang, Zhang, Wei, Du, Zhang, Yang, Zhang, Gong, Li, Song, Xu, He, Zhou, Zheng, Sun and Luo.)