NK92 cells and peripheral blood NK cells respond oppositely upon dasatinib treatment.

Natural killer (NK) cell is a valuable tool for immunotherapy in cancer treatment, both the cultured cell line NK92 and primary NK cells are widely studied and used in research and clinical trials. Clinical observations witnessed the improvement of patients' NK cells in terms of cell counts and cytotoxic activity upon dasatinib treatment, an approved drug for chronic myeloid leukaemia and Ph+ acute lymphocytic leukaemia. Several studies supported the clinical observations, yet others argued a detrimental effect of dasatinib on NK cells. Due to the complex conditions in different studies, the definite influence of dasatinib on NK92 and primary NK cells remains to be settled. Here, we used a well-defined in vitro system to evaluate the effects of dasatinib on NK92 cells and peripheral blood (PB)-NK cells. By co-culturing NK cells with dasatinib to test the cell counts and target cell-killing activities, we surprisingly found that the chemical influenced oppositely on these two types of NK cells. While dasatinib suppressed NK92 cell proliferation and cytotoxic activity, it improved PB-NK-killing tumour cells. RNA sequencing analysis further supported this finding, uncovering several proliferating and cytotoxic pathways responding invertedly between them. Our results highlighted an intrinsic difference between NK92 and PB-NK cells and may build clues to understand how dasatinib interacts with NK cells in vivo.

The Relation between Immunological Features and the Positive SARS-CoV-2 Nucleic Acid in Patients with Nonsevere COVID⁃19.

Objective: The novel coronavirus nucleic acid results are the core indicators of illness monitoring. This study aimed to evaluate the relationship between immunological features and positive SARS-CoV-2 nucleic acid by analyzing the clinical and immunological features in nonsevere COVID-19 cases. Methods: Data from nonsevere COVID-19 patients admitted to Haihe Hospital from May 2020 to June 2021 were retrospectively reviewed and analyzed. Results: (1) A total of 122 cases were reviewed in the present study, including 38 mild and 84 moderate cases. The average age of mild cases was significantly different from moderate cases (P < 0.001). Eight patients complained of hyposmia and it was more frequent in mild cases (P < 0.001). The nucleic acid positive duration (NPD) of nonsevere novel coronavirus was 20.49 (confidence interval (CI) 17.50-3.49) days. (2) The levels of specific IgM and IgG for COVID-19 were higher in mild cases than in moderate cases (P=0.023 and P=0.047, respectively). (3) The correlation analysis with antibodies and T-cell subtypes showed that the lymphocyte (LYM) count, T cells, CD4+T cells, and CD8+T cells had a linear correlation with NPD. (4) Among the 93 patients monitored, 62 COVID-19 cases presented a progressive rise of specific IgM and IgG. The daily increase rates of IgM and IgG were 38.42% (CI 28.22-48.61%) and 24.90% (CI 0.23-29.58%), respectively. Conclusion: The levels and daily increase rates of specific IgM and IgG against the virus can vary between cases. The NPD presented a linear correlation with the LYM, T cells, CD4+T cells, and CD8+T cells. Hence, more attention should be paid to these indicators in clinical practice.

Efficacy, safety, and tolerability of combined pirfenidone and N-acetylcysteine therapy: a systematic review and meta-analysis.

BACKGROUND: While antifibrotic drugs significantly decrease lung function decline in idiopathic pulmonary fibrosis (IPF), there is still an unmet need to halt disease progression. Antioxidative therapy with N-acetylcysteine (NAC) is considered a potential additional therapy that can be combined with antifibrotics in some patients in clinical practice. However, data on the efficacy, tolerability, and safety of this combination are scarce. We performed a systematic review and meta-analysis to appraise the safety, tolerability, and efficacy of the combination compared to treatment with pirfenidone alone. METHODS: We systematically reviewed all the published studies with combined pirfenidone (PFD) and NAC (PFD + NAC) treatment in IPF patients. The primary outcomes referred to decline in pulmonary function tests (PFTs) and the rates of IPF patients with side effects. RESULTS: In the meta-analysis, 6 studies with 319 total IPF patients were included. The PFD + NAC group was comparable to the PFD alone group in terms of the predicted forced vital capacity (FVC%) and predicted diffusion capacity for carbon monoxide (DLco%) from treatment start to week 24. Side effects and treatment discontinuation rates were also comparable in both groups. CONCLUSION: This systematic review and meta-analysis suggests that combination with NAC does not alter the efficacy, safety, or tolerability of PFD in comparison to PFD alone in IPF patients.

Salvianolic acid B protects against paraquat-induced pulmonary injury by mediating Nrf2/Nox4 redox balance and TGF-ß1/Smad3 signaling.

The present study was aimed at exploring the protective effects of Salvianolic acid B (SalB) against paraquat (PQ)-induced lung injury in mice. Lung fibrotic injuries were induced in mice by a single intragastrical administration of 300mg/kg PQ, then the mice were administrated with 200mg/kg, 400mg/kg SalB, 100mg/kg vitamin C (Vit C) and dexamethasone (DXM) for 14days. PQ-triggered structure distortion, collagen overproduction, excessive inflammatory infiltration, pro-inflammatory cytokine release, and oxidative stress damages in lung tissues and mortality of mice were attenuated by SalB in a dose-dependent manner. Furthermore, SalB was noted to enhance the expression and nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and reduce expression of the reactive oxygen species-generating enzyme Nox4 [NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase-4]. SalB also inhibited the increasing expression of transforming growth factor (TGF)-ß1 and the phosphorylation of its downstream target Smad3 which were enhanced by PQ. These results suggest that SalB may exert protective effects against PQ-induced lung injury and pulmonary fibrosis. Its mechanisms involve the mediation of Nrf2/Nox4 redox balance and TGF-ß1/Smad3 signaling.

[A comparison study of diagnostic value between the old and revised guidelines in patients with idiopathic pulmonary fibrosis].

OBJECTIVE: To compare the strengths and limitations of the old and revised guidelines for the diagnosis in patients with idiopathic pulmonary fibrosis(IPF). METHODS: Patients who were admitted and diagnosed as interstitial lung diseases (ILDs) in our hospital from 2009 to 2014 were enrolled in our study.Eachpatient was reevaluated respectively according to the old and revised guidelines of IPF. RESULTS: A total of 553 cases were initially reviewed, among whom 355 cases were excluded for pulmonary fibrosis secondary to definite underlying diseases, 28 excluded due to high resolution computed tomography(HRCT) not done, 26 excluded because serum immunology examination was not available.The remaining 144 cases were finally enrolled in this study including 92 males and 52 females with median age 21-92 (68 ± 11) years old. Twenty five patients (17.4%, 25/144) met the diagnostic criteria of IPF by the old guideline.While by the revised guideline, 53 patients (36.8%, 53/144) were diagnosed as classical IPF, 29 patients(20.1%, 29/144) as probable cases, another 69 non-IPF patients accounting for 43.1% (62/144). The result revealed that there's a significant difference between the two guidelines in the diagnosis of IPF. CONCLUSIONS: The revised guideline favors an early diagnosis of IPF and simplifies the diagnostic process.However the possibility of over diagnosis or missed diagnosis by the revised guideline does exist.On the other hand, despite of the delayed diagnosis by the old guideline, it may reduce the misdiagnosis of IPF in some circumstance.

1-Naphthaleneacetic Acid Improved the In Vitro Cell Culturing by Inhibiting Apoptosis.

In vitro cell culturing witnessed its applications in scientific research and industrial activities. Attempts to shorten the doubling time of cultured cells have never ceased. In plants, auxin is applied to promote plant growth, the synthetic derivative 1-Naphthaleneacetic acid (NAA) is a good example. Despite the auxin's naturally occurring receptors are not present in mammalian cells, studies suggested they may affect cell culturing. Yet the effects and mechanisms are still unclear. Here, an up to 2-fold increase in the yield of in vitro cultured human cells is observed. Different types of human cell lines and primary cells are tested and found that NAA is effective in all the cells tested. The PI staining followed by FACS suggested that NAA do not affect the cell cycling. Apoptosis-specific dye staining analysis implicated that NAA rescued cell death. Further bulk RNA sequencing is done and it is identified that the lipid metabolism-engaging and anti-apoptosis gene, ANGPTL4, is enhanced in expression upon NAA treatment. Studies on ANGPTL4 knockout cells indicated that ANGPTL4 is required for NAA-mediated response. Thus, the data identified a beneficial role of NAA in human cell culturing and highlighted its potency in in vitro cell culturing.

Nerandomilast Improves Bleomycin-Induced Systemic Sclerosis-Associated Interstitial Lung Disease in Mice by Regulating the TGF-ß1 Pathway.

Systemic sclerosis (SSc) is a rare connective tissue disease with a heterogeneous clinical course. Interstitial lung disease (ILD) is a common complication of SSc and a major contributor to SSc-related deaths. Besides nintedanib and tocilizumab, there are currently no clinically approved drugs for SSc-ILD, highlighting the urgent need for new treatment strategies. Previous studies have shown that cyclic adenosine monophosphate (cAMP) plays a crucial role in the pathogenesis of SSc and lung fibrosis. Phosphodiesterases (PDEs) are enzymes that specifically hydrolyze cAMP, making PDE inhibitors promising candidates for SSc-ILD treatment. Nerandomilast, a preferential phosphodiesterase 4B (PDE4B) inhibitor currently undergoing phase III clinical trials for idiopathic pulmonary fibrosis and progressive fibrosing interstitial lung diseases (PF-ILD), has good preference for PDE4B but lacks studies for SSc-ILD. Our research demonstrates that nerandomilast effectively inhibits skin and lung fibrosis in a bleomycin-induced mouse model of SSc-ILD. For lung fibrosis, we found that nerandomilast could improve bleomycin-induced SSc-ILD through inhibiting PDE4B and the TGF-ß1-Smads/non-Smads signaling pathways, which provides a theoretical basis for potential therapeutic drug development for SSc-ILD.

[The correlation of helper T lymphocyte 1/helper T lymphocyte 2 with clinical and image features in patients with idiopathic pulmonary fibrosis].

OBJECTIVE: To identify whether the helper T lymphocyte 1 (Th1)/helper T lymphocyte 2 (Th2) of patients' serum and bronchoalveolar lavage fluid (BALF) at admission could represent the severity of idiopathic pulmonary fibrosis (IPF) and whether its change at six months could predict the progression of the disease. METHODS: Eighty-three patients with IPF were subjected to pulmonary function tests (PFTs), dyspnea scores, arterial blood gas analysis, six-minute walk test (6MWT) and high-resolution computed tomography (HRCT). The serum and BALF specimen of these patients were obtained as well as 20 control serum and 10 control BALF specimen. A total of 55 patients were followed up, and their BALF and serum levels of interferon γ(IFNγ) and IL-4 were detected by enzyme-linked immunoadsorbent assay (ELISA). The correlation between the IFNγ/IL-4 levels (at admission and the change of that at six months follow-up) and the clinical, physiological and image features in the IPF patients were analyzed. RESULTS: The baseline serum and BALF level of IFNγ/IL-4 (0.8 ± 0.3) in the IPF patients was lower than that in the control group (1.4 ± 0.2), which showed significant correlation with the course of disease, dyspnea scores, FEV1%, FVC%, TLC%, maximum desaturation, 6MWD and CT-fib (all P values<0.05). The serum level of IFNγ/IL-4 showed positive correlation with CT-alv (r = 0.340, P<0.01). During follow-up, no statistic difference was found in the serum levels of IFNγ, IL-4 and IFNγ/IL-4 between the IPF patients with or without glucocorticoids treatment. There were significant aggravation in the dyspnea scores, FEV1%, FVC%, CT-alv, CT-fib, IFNγ and IL-4 at six months follow-up. Significant correlation had been showed between the change of the serum IFNγ/IL-4 level with the changes of the dyspnea scores, FVC%, TLC%, DLCO%, 6MWD and CT-fib in the IPF patients (P < 0.05). CONCLUSIONS: There are disequilibrium of the Th1/Th2 in the serum and the BALF of the IPF patients. The Th1/Th2 level could represent severity of the disease, and the serum level change of Th1/Th2 in the follow-up could predict the progression of the diseases in the IPF patients.

[Screening of potential proteins from patients with idiopathic pulmonary fibrosis by using of surface enhanced laser desorption/ionization time of flight mass spectrum].

OBJECTIVE: To screen potential proteins in bronchoalveolar lavage fluid (BALF) and serum samples obtained from patients with idiopathic pulmonary fibrosis (IPF), for the purpose of discovering candidate biomarkers. METHODS: BALF and serum samples from 34 patients diagnosed IPF (IPF group) and 25 non-smoker healthy controls (control group) were collected. Surface enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS) was used to obtain protein fingerprints from BALF and serum samples. Biomarker Wizard and Biomarker Pattern were introduced in bioinformatics analysis. RESULTS: A total of 247 protein peaks were detected in BALF, and 13 peaks with statistical difference compared with control group. Among 13 detected protein peaks, 7 with mass/charge ratio (M/Z) values of 2240.57, 3459.32, 3501.78, 4146.50, 4516.51, 4615.88, 5651.26 were statistically up-regulated (all P < 0.01); and 6 peaks with M/Z values of 4989.91, 5043.68, 6968.76, 11 687.70, 11 782.10, 14 733.30 were significantly down-regulated (all P < 0.01). In addition, 142 protein peaks were differentially expressed in serum samples, and 9 peaks with statistical differences. Among them, 9 peaks with M/Z values of 3382.59, 3453.39, 4608.28, 5825.48, 8936.76, 9164.27, 11 525.30, 11 689.40 and 11 886.00 were significantly up-regulated (P < 0.05 or P < 0.01), compared with control group. CONCLUSIONS: The present work demonstrated that SELDI-TOF-MS technology be capable of detecting differentially expressed protein peaks in BALF and serum samples from IPF patients. Further investigations were guaranteed to elucidate their potential diagnostic value in clinical practice.

Epigenetics alternation in lung fibrosis and lung cancer.

Respiratory disease including interstitial lung diseases (ILDs) and lung cancer is a group of devastating diseases that linked with increased morbidity and healthcare burden. However, respiratory diseases cannot be fully explained by the alternation of genetic information. Genetic studies described that epigenetic mechanisms also participate to transmit genetic information. Recently, many studies demonstrated the role of altered epigenetic modification in the pathogenesis of lung cancer and pulmonary fibrosis. Due to lacking effective medication, the underlying pathophysiological processes and causal relationships of lung diseases with epigenetic mechanisms still need to be better understood. Our present review provided a systematic revision of current knowledge concerning diverse epigenetic aberrations in major lung diseases, with special emphasis on DNA methylation, histone modifications, lncRNAs profiles, telomere patterns, as well as chromatin-remodelling complexes. We believed that a new target therapy for lung disease based on findings of the involved epigenetic pathway is a promising future direction.

Temporal and Spatial Characterization of Mononuclear Phagocytes in Circulating, Pulmonary Alveolar, and Interstitial Compartments in LPS-Induced Acute Lung Injury.

Peripheral circulating monocytes and resident macrophages are heterogeneous effector cells that play a critical role in the maintenance and restoration of pulmonary integrity. However, their detailed dynamic changes in lipopolysaccharide (LPS)-induced acute lung injury (ALI) remain unclear. Here, we investigated the impact of mononuclear phagocyte cells in the development of LPS-induced ALI/Acute respiratory distress syndrome (ARDS) and described the relations between the dynamic phenotypic changes and pulmonary pathological evolution. In this study, mice were divided into two groups and intraperitoneally injected with normal saline (NS) or LPS, respectively. A series of flow cytometry assay was performed for the quantification of peripheral circulating monocyte subpopulations, detection of the polarization state of bronchoalveolar lavage fluid (BALF)-isolated alveolar macrophages (AMϕ) and pulmonary interstitial macrophages (IMϕ) separated from lung tissues. Circulating Ly6Clo monocytes expanded rapidly after the LPS challenge on day 1 and then decreased to day 7, while Ly6Chi monocytes gradually increased and returned to normal level on the 7th day. Furthermore, the expansion of M2-like AMϕ (CD64+CD206+) was peaked on day 1 and remained high on the third day, while the polarization state of IMϕ (CD64+ CD11b+) was not influenced by the LPS challenge at all the time points. Taken together, our findings show that Ly6Clo monocytes and M2-like AMϕ form the major peripheral circulation and pulmonary immune cell populations, respectively. The dynamic changes of mononuclear phagocyte in three compartments after the LPS challenge may provide novel protective strategies for mononuclear phagocytes.

High-resolution computed tomography (HRCT) analysis in anti-synthase antibody syndrome with organizing pneumonia.

OBJECTIVE: The organizing pneumonia (OP) pattern is the second most common finding in anti-synthase antibody syndrome (ASS), and nonspecific interstitial pneumonia (NSIP) is the most common finding. This study analysed the OP score changes by semiquantitative and quantitative analysis methods and the correlation between the high-resolution computed tomography (HRCT) indexes and the pulmonary function test parameters (PFTs) in ASS patients. METHODS: Data from ASS-OP patients admitted to the respiratory department of Ping Jin Hospital from October 2014 to June 2020 were retrospectively reviewed and analysed. RESULTS: Fourteen ASS-OP patients were recruited for this study. (1) In method-1, the consolidation (CO) score and the mean lung attenuation (MA) of poorly aerated and fibrosis lung fields (MAfibrosis) (r=0.56, P=0.04), the ground-glass opacity (GGO) score and the MA of non-aerated lung fields (MAnonaerated) (r=-0.64, P=0.01), and the CO plus the GGO (CG) score and the MAnonaerated (r=-0.59, P=0.03) of the lung fields had liner correlations. In method-2, the GGO score to the MAnonaerated (r=-0.58, P=0.03), and the CG (r=-0.68, P=0.01) score to the MAnonaerated had liner correlations. The FVC% (r=0.68, P=0.01) and FEV1% (r=0.64, P=0.01) to the MAfibrosis had good linear correlations. (2) Compared to the values before treatment, the CO pattern score, volume and weight percentages of the extracted whole lung volume with attenuation values of the nonaerated area (Vnonated%, Wnonaerated%), the volume of poorly aerated and fibrosis lung tissue (Vfibrosis%, Wfibrosis%), the weight percentages of normal aerated lung (Wnormal%), and the MAfibrosis exhibited significant differences during the 3-6 month follow-up period. CONCLUSION: The GGO and CO scored by the semiquantitative or quantitative analysis methods was similar. The HRCT quantitative analysis parameters showed a good correlation with the PFTs in ASS-OP patients, can provide an accurate OP pattern interpretation, and may be used as a monitoring and therapeutic indicator for ASS-OP patients.

Chemical reagents modulate nucleic acid-activated toll-like receptors.

Nucleic acid-mediated interferon signaling plays a pivotal role in defense against microorganisms, especially during viral infection. Receptors sensing exogenous nucleic acid molecules are localized in the cytosol and endosomes. Cytosolic sensors, including cGAS, RIG-I, and MDA5, and endosome-anchored receptors are toll-like receptors (TLR3, TLR7, TLR8, and TLR9). These TLRs share the same domain architecture and have similar structures, facing the interior of endosomes so their binding to nucleic acids of invading pathogens via endocytosis is possible. The correct function of these receptors is crucial for cell homeostasis and effective response against pathogen invasion. A variety of endogenous mechanisms modulates their activities. Nevertheless, naturally occurring mutations lead to aberrant TLR-mediated interferon (IFN) signaling. Furthermore, certain pathogens require a more robust defense against control. Thus, manipulating these TLR activities has a profound impact. High-throughput virtual screening followed by experimental validation led to the discovery of numerous chemicals that can change these TLR-mediated IFN signaling activities. Many of them are unique in selectivity, while others regulate more than one TLR due to commonalities in these receptors. We summarized these nucleic acid-sensing TLR-mediated IFN signaling pathways and the corresponding chemicals activating or deactivating their signaling.

[Effect of corticosteroids upon the prognosis of idiopathic pulmonary fibrosis].

OBJECTIVE: To investigate the therapeutic effect of corticosteroids upon idiopathic pulmonary fibrosis (IPF) and the impact of corticosteroids upon survival time. METHODS: Clinical data of 94 corticosteroid treatment and 32 non-corticosteroid treatment IPF patients during 2000 - 2004 were retrospectively analyzed and their survival rates compared between two groups. The corticosteroid treatment patients were divided into 3 groups: improved, steady and worsened group according to the pulmonary function data. Therapeutic effects and survival rates were compared between these 3 groups. RESULTS: In the treatment group, 6 (6.4%) patients could not be located, 22 (23.4%) patients survived, and 66 (70.2%) patients died. In the non-corticosteroid treatment group, 1 (3.1%) patients could not be located, 2 (6.3%) patients survived and 29 (90.6%) patients died. No statistically significant difference existed between the two groups (P > 0.05). Sixty-two corticosteroid treatment patients were followed up for 3-6 months. Among them, 19 (30.7%) patients improved, 11 (17.7%) patients remained steady and 32 (51.6%) patients worsened in pulmonary function. In 19 improved patients, 7 (36.8%) survived and 12 (63.2%) died. In 11 steady patients, 3 (27.2%) survived and 8 (72.7%) died. In 32 worsened patients, 3 (9.4%) could not be located, 1(3.1%) survived and 28 (87.5%) died. The survival rate of the improved and steady groups was higher than that of the worsened group (P < 0.01). CONCLUSIONS: There is some therapeutic effect of corticosteroids in the early alveolitis stage of IPF. The prognosis of the patients with improved and steady pulmonary function parameters during the first 3 - 6 months is better than that of worsened patients.

[A retrospective cohort study of prognostic factors for death in patients with idiopathic pulmonary fibrosis].

OBJECTIVE: To investigate the prognostic implications of clinical, radiographic, and physiological variables in idiopathic pulmonary fibrosis (IPF). METHODS: The clinical, pulmonary physiological, bronchoalveolar lavage fluid (BALF) cell differentials and lung high-resolution computed tomography (HRCT) at diagnosis in 126 patients with IPF were retrospectively analyzed. Univariate and multivariate Cox proportional-hazards regression analysis was used to evaluate various parameters associated with hazard ratio (HR). The survival rates of all groups were compared using the Kaplan-Meier method. RESULTS: In 29.6 months of average follow-up time, the survival rate of the IPF patients was 46.8% (59/126), and the median survival time was 30 months after diagnosis. Glucocorticoids and/or cytotoxic drugs for patients with IPF did not change the prognosis. The survival rates between groups by gender and smoking status showed no statistically significant difference (Ward: 0.11, 1.65, P>0.05). The patients were divided into 2 groups by the median (the cutoff point value) of significant variables in univariate Cox proportional-hazards regression analysis, and the survival rates showed statistically significant difference by dyspnea scale, FVC%, TLC%, DLCO%, neutrophil percentage and eosinophil percentage in BALF, and the reticular and honeycomb lung score (Logrank: 13.52-57.52, P<0.05). The results of multivariate Cox proportional-hazards regression analysis showed that TLC%, DLCO%, HRCT reticular score and honeycomb lung score were factors that affected the prognosis of patients with IPF (Wald=5.76-21.48, P<0.05). CONCLUSIONS: TLC%, DLCO%, cell differentials of BALF and the degree of pulmonary fibrosis were the main factors affecting the prognosis of patients with IPF. TLC% and DLCO% showed a negative correlation with the prognosis of patients with IPF. Glucocorticoids and/or cytotoxic drug therapy had no effect on the prognosis of patients with IPF.

Blood purification in two patients with clinically amyopathic dermatomyositis associated with interstitial lung disease with anti-melanoma differentiation-associated gene-5 antibody (MDA-5).

Patients of clinically amyopathic dermatomyositis associated with rapidly progressive interstitial pneumonia (CADM-RFIP) with positive anti-MDA5 antibody usually presents rapid deterioration and traditional therapy such as cyclophosphamide combined with high-dose prednisone pulse therapy shows no clear benefit at whiles. However, blood purification combined with traditional therapy works according to the literature. We herein report two CADM-RFIP patients administered with DNA immunoadsorption combined with traditional therapy and then reviewed the literature of blood purification in CADM-RFIP patients at home and abroad to date. We emphasize blood purification such as DNA immunoadsorption could apply in the early stage of CADM-RFIP, which can decrease inflammation and allow us more time to control the condition better.

Cross-sectional and longitudinal construct validity of the Saint George's Respiratory Questionnaire in patients with IPF.

BACKGROUND AND OBJECTIVE: This study was performed to confirm the cross-sectional and longitudinal construct validity of the Saint George's Respiratory Questionnaire (SGRQ) for the measurement of health-related quality of life (HRQoL) in patients with IPF. METHODS: Sixty-eight patients with IPF responded to the SGRQ and pulmonary function tests (PFT), dyspnoea testing, arterial blood gas analysis, 6-min walk tests (6MWT) and high-resolution computed tomography were performed in a baseline study. A follow-up study was performed on 45 of these patients. RESULTS: In the baseline study HRQoL as measured by the SGRQ was substantially impaired in IPF patients, especially in symptoms and activity domains. A significant decline in HRQoL was observed in the activity domain during follow up. TLC and changes in TLC showed the most significant inverse correlations with each SGRQ domain (r < -0.3, P < 0.05). In a stepwise multiple regression analysis, TLC contributed most significantly to each SGRQ component baseline score. Similar results were also observed during follow up. There was a significant correlation between total CT scores and each component of the SGRQ (r > 0.3, P < or = 0.001). Changes in ground-glass opacity on CT (CT-alv) were also correlated with changes in each SGRQ domain (r > 0.3, P < or = 0.001). Stepwise multiple regression analysis showed that interstitial opacity on CT (CT-fib) contributed to variation in the baseline activity score, and that changes in CT-alv independently contributed to overall changes in the SGRQ domains during follow up. The dyspnoea score, and changes in the dyspnoea score, correlated significantly with the SGRQ sores, with the exception of the symptoms score, in both the baseline and follow-up studies. CONCLUSIONS: HRQoL as assessed by the SGRQ showed good cross-sectional and longitudinal construct validity in patients with IPF. However, additional studies are required to analyse the reliability and responsiveness so that the SGRQ can be used in patients with IPF.

[Cell profiles of bronchoalveolar lavage fluid as prognostic indicators of idiopathic pulmonary fibrosis].

OBJECTIVE: To determine whether clinical and physiologic variables and bronchoalveolar lavage fluid (BALF) cell profiles affect the survival of patients with idiopathic pulmonary fibrosis (IPF). METHODS: There were 43 patients with clinically diagnosed IPF in the study. The Kaplan-Meier method and the Log-rank test were used to estimate the survival in the two groups and Cox proportional hazard regression was used to evaluate the Hazard Ratio in the IPF patients. RESULTS: The IPF patients presented with restrictive ventilatory disorders [FVC%: (61 +/- 18)%, TLC%: (54 +/- 13)%] and gas exchange impairment [D(L)CO%: (48 +/- 14)%]. The mean follow-up time was 30.7 months, and the median survival of IPF patients was 28.5 months after diagnosis. FVC ( Wald = 6.71, P < 0.01), TLC ( Wald = 12.37, P < 0.01) , D(L)CO ( Wald = 22.78, P < 0.01), neutrophil ( Wald = 16.26, P < 0.01) and eosinophil ( Wald = 7.73, P < 0.01) percentages were prognostic variables in the univariate Cox proportional hazard regression, and only D(L)CO (HR = 0.93, Wald = 15.77, P < 0.01) and the neutrophil percentage (HR = 1.07, Wald = 6.83, P < 0.01) were prognostic variables for IPF patients in the multivariate Cox proportional hazard regression. CONCLUSIONS: The IPF patients were predominantly old males and presented with restrictive ventilatory disorders and gas exchange impairment. Glucocorticoids and/or cytotoxic drugs could not improve the prognosis for the IPF patients. DLCO and BALF neutrophil percentage were prognostic variables, and DLCO was negatively correlated with the prognosis while the neutrophil percentage was positively correlated with the prognosis in the IPF patients.

Paeoniflorin inhibits PDGF­BB­induced human airway smooth muscle cell growth and migration.

Abnormal proliferation and migration of airway smooth muscle cells (ASMCs) is important in the progression of asthma. Paeoniflorin (PF), one of the major active ingredients of Paeonia lactiflora, has been reported to exhibit anti­asthmatic effects. However, the effects of PF in the regulation of platelet­derived growth factor (PDGF)­BB­induced ASMC proliferation and migration remain unknown. The present study was designed to investigate the effects of PF on human ASMCs and the underlying mechanism. The results demonstrated that PF treatment significantly reduced the numbers of live ASMC cells and their PDGF­BB­induced migration. PF treatment also suppressed PDGF­BB­induced α­smooth muscle actin expression in ASMCs. Furthermore, pretreatment with PF reduced PDGF­BB­induced phosphorylation of phosphoinositide 3­kinase (PI3K) and AKT serine/threonine kinase 1 (Akt) in ASMCs. In conclusion, the present study demonstrated for the first time that PF inhibited ASMC growth and migration induced by PDGF­BB, and that this effect may be partly due to inhibition of the PI3K/Akt signaling pathway. The results provide novel information regarding the role of PF as a potential therapeutic agent for the treatment of asthma.