Tanshinone IIA ameliorates energy metabolism dysfunction of pulmonary fibrosis using 13C metabolic flux analysis

Evidence indicates that metabolic reprogramming characterized by the changes in cellular metabolic patterns contributes to the pathogenesis of pulmonary fibrosis (PF). It is considered as a promising therapeutic target anti-PF. The well-documented against PF properties of Tanshinone IIA (Tan IIA) have been primarily attributed to its antioxidant and anti-inflammatory potency. Emerging evidence suggests that Tan IIA may target energy metabolism pathways, including glycolysis and tricarboxylic acid (TCA) cycle. However, the detailed and advanced mechanisms underlying the anti-PF activities remain obscure. In this study, we applied [U-13C]-glucose metabolic flux analysis (MFA) to examine metabolism flux disruption and modulation nodes of Tan IIA in PF. We identified that Tan IIA inhibited the glycolysis and TCA flux, thereby suppressing the production of transforming growth factor-β1 (TGF-β1)-dependent extracellular matrix and the differentiation and proliferation of myofibroblasts in vitro. We further revealed that Tan IIA inhibited the expression of key metabolic enzyme hexokinase 2 (HK2) by inhibiting phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor 1α (HIF-1α) pathway activities, which decreased the accumulation of abnormal metabolites. Notably, we demonstrated that Tan IIA inhibited ATP citrate lyase (ACLY) activity, which reduced the collagen synthesis pathway caused by cytosol citrate consumption. Further, these results were validated in a mouse model of bleomycin-induced PF. This study was novel in exploring the mechanism of the occurrence and development of Tan IIA in treating PF using 13C-MFA technology. It provided a novel understanding of the mechanism of Tan IIA against PF from the perspective of metabolic reprogramming.

Effect of surfactant Tween-80 on sulfur oxidation and expression of sulfur metabolism relevant genes of Acidithiobacillus ferrooxidans

The effects of surfactant Tween-80 on the growth, sulfur oxidation, and expression of selected typical sulfur metabolism relevant genes of Acidithiobacillus ferrooxidans ATCC 23270 were investigated. The results showed that in the presence of 10-2 g/L Tween-80, the growth of A. ferrooxidans and its metabolism on the insoluble substrate S0 and CuFeS2 were promoted. After 24 d of bioleaching, the copper extraction yield of chalcopyrite at 10-2 g/L Tween-80 increased by 16% compared with the bioleaching experiment without Tween-80. FT-IR spectra analysis revealed that the result was probably caused by the extracellular polymeric substances whose composition could be changed by the surfactant addition. RT-qPCR was used to analyze the differential expressions of 17 selected sulfur metabolism relevant genes in response to the addition of Tween-80. Down-regulation of the extracellular protein genes indicated the influence of Tween-80 on bacteria-sulfur adsorption. Variation of the expression level of the enzymes provided a supplement to sulfur metabolism investigation.

Effects of pulmonary surfactant combined with noninvasive positive pressure ventilation in neonates with respiratory distress syndrome

BACKGROUND Neonatal respiratory distress syndrome(NRDS)is one of the most common diseases in neonatal intensive care units,with an incidence rate of about 7%among infants.Additionally,it is a leading cause of neonatal death in hospitals in China.The main mechanism of the disease is hypoxemia and hypercapnia caused by lack of surfactant AIM To explore the effect of pulmonary surfactant(PS)combined with noninvasive positive pressure ventilation on keratin-14(KRT-14)and endothelin-1(ET-1)levels in peripheral blood and the effectiveness in treating NRDS.METHODS Altogether 137 neonates with respiratory distress syndrome treated in our hospital from April 2019 to July 2021 were included.Of these,64 control cases were treated with noninvasive positive pressure ventilation and 73 observation cases were treated with PS combined with noninvasive positive pressure ventilation.The expression of KRT-14 and ET-1 in the two groups was compared.The deaths,complications,and PaO_(2),PaCO_(2),and PaO_(2)/FiO_(2)blood gas indexes in the two groups were compared.Receiver operating characteristic curve(ROC)analysis was used to determine the diagnostic value of KRT-14 and ET-1 in the treatment of NRDS.RESULTS The observation group had a significantly higher effectiveness rate than the control group.There was no significant difference between the two groups in terms of neonatal mortality and adverse reactions,such as bronchial dysplasia,cyanosis,and shortness of breath.After treatment,the levels of PaO_(2)and PaO_(2)/FiO_(2)in both groups were significantly higher than before treatment,while the level of PaCO_(2)was significantly lower.After treatment,the observation group had significantly higher levels of PaO_(2)and PaO_(2)/FiO_(2)than the control group,while PaCO_(2)was notably lower in the observation group.After treatment,the KRT-14 and ET-1 levels in both groups were significantly decreased compared with the pre-treatment levels.The observation group had a reduction of KRT-14 and ET-1 levels than the control group.ROC curve analysis showed that the area under the curve(AUC)of KRT-14 was 0.791,and the AUC of ET-1 was 0.816.CONCLUSION Combining PS with noninvasive positive pressure ventilation significantly improved the effectiveness of NRDS therapy.KRT-14 and ET-1 levels may have potential as therapeutic and diagnostic indicators.

Osthole attenuates pulmonary arterial hypertension by modulation of phospholipid metabolism

OBJECTIVE Pulmonary arterial hypertension(PAH)is a malignant pulmonary vascular disease lacking efficacy therapeutics.Therefore,it urgently needs to develop safe and effective drugs for PAH treatment.Osthole derived from Cnidium monnieri(L.)Cusson(Shechuangzi)or Angelica pubescens Maxim(Duhuo)has the capacity to alleviate PAH by decreasing pulmonary arterial pressure and alleviating pulmonary vascular remodeling in rats,which is a candidate drug for the prevention of PAH,but the underlying modulatory mechanism is still unclear.Our study aims at investigating the metabolic modulatory mechanism of osthole against PAH employing functional metabolomics strategy.METHODS PAH model rats were successfully established with MCT,following osthole administration,then functional metabolomics based on untargeted metabolomics assay,targeted lipidomics analysis,qRT-PCR,Western blotting and ELISA were performed to investigate the modulatory mechanism of osthole against pulmonary arterial pressure and pulmonary vascular remodeling in PAH.RESULTS Untargeted metabolomics results found that sphingosine 1-phosphate(S1P)was the differential metabolites characterized PAH and reversed by osthole treatment.S1P is a crucial sphingolipid metabolite catalyzed by sphingosine kinases1(Sphk1)and functions as promoting PASMCs proliferation contributing to pulmonary vascular remodeling and pulmonary arterial pressure increase.We revealed that osthole reversed high level of S1P by modulating metabolic enzyme Sphk1 via inactivating microRNA-21-PI3K/Akt/mTOR signal pathway to decrease pulmonary arterial pressure in rats with PAH.Then,targeted phospholipid metabolomics results uncovered that decadienyl-L-carnitine(C10:2)was the differential metabolite characterized PAH and corrected by osthole treatment in rat with PAH.C10:2 is the intermediate metabolite of fatty acid oxidation(FAO),and C10:2 accumulation indicated mitochondrial dysfunction and FAO increase.CONCLUSION Osthole could block lipid metabolic reprogramming through functional modulating the expression of fatty acid translocase,fatty acid synthase,phospholipase A2,carnitine palmitoyltransferase 1A to inhibit C10:2,thus to improve mitochondrial dysfunction and inhibit utilizing lipid to biosynthesize necessary essence for pulmonary artery smooth muscle cells(PASMCs)proliferation.Moreover,we delineated that C10:2 and metabolic reprogramming enzymes were modulated by miRNA-22-3p which was involved in PASMCs proliferation and pulmonary vascular remodeling.Therefore,osthole inhibited miRNA-22-3p mediated lipid metabolic reprogramming to ameliorate pulmonary vascular remodeling.

Surfactant Protein B 1580 Polymorphism Is Associated with Susceptibility to Chronic Obstructive Pulmonary Disease in Chinese Han Population

Summary: Whether surfactant protein B (SP-B)-18A/C and 1580C/T polymorphism were associated with susceptibility to chronic obstructive pulmonary disease (COPD) in Chinese Han population was investigated. After genomic DNA was isolated from blood of COPD smokers and control smokers, the genotypes of SP-B-18A/C and SP-B1580C/T polymorphism loci were determined by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) respectively. The results showed that there was significant difference in genotypes distribution frequency of SP-B1580C/T polymorphism locus between COPD smokers and control smokers. C→T mutation rate (including TT homozygote and CT heterozygote) in COPD smokers was higher than in control smokers (57.9 % vs 41.7 %, χ2=4.93, P<0.05), whereas there was no significant difference in genotypes distribution frequency of SP-B1580-18A/C locus between COPD smokers and control smokers. The allele frequency (29.1 %) of SP-B1580-18A/C locus is lower than T allele (70.9 %) in Chinese Han Population, and the distribution was different from that in Mexican, in which, the A and T allele frequencies were 85 % and 15 % respectively. It was concluded that SP-B1580 T allele was probably associated with increased susceptibility to COPD in Chinese Han population; The polymorphism of SP-B-18A/C locus maybe varied with race.

Early Intratracheal Administration of Corticosteroid and Pulmonary Surfactant for Preventing Bronchopulmonary Dysplasia in Preterm Infants with Neonatal Respiratory Distress Syndrome: A Meta-analysis

There is uncertain result with regard to the use of inhalation or instillation steroids to prevent bronchopulmonary dysplasia in preterm infants. This meta-analysis was designed to evaluate the efficacy and safety of early airway administration (within 2 days after birth) of corticosteroids and pulmonary surfactant (PS) for preventing bronchopulmonary dysplasia (BPD) in premature infants with neonatal respiratory distress syndrome (NRDS). The related studies were retrieved in PubMed, EMBASE, the Cochrane Library, Clinical Trial, CNKI, Wanfang and VIP Database from inception to August 2018. Two reviewers independently screened the studies to ensure that all patients with diagnosis of NRDS were enrolled to studies within 1 day after birth, assessed the quality of included studies by GRADEpro system and extracted the data for review. The meta-analysis was performed by RevMan 5.2 software. A subgroup analysis about inhaled corticosteroid (ICS) delivery method was made between ICS inhalation subgroup [inhalation of ICS by nebulizer or metered dose inhaler (MDI)] and ICS intratracheal instillation subgroup (PS used as a vehicle). Eight randomized controlled trials were enrolled in the meta-analysis, 5 trials of which stated the randomized method, grouping and blinded method, and the follow-up procedures were reported. GRADEpro system showed high quality of 4 trials (5 articles), and the rest 4 trials had moderate quality. Meta-analysis showed that the incidence of BPD was decreased in ICS group, the relative risk (RR) was 0.56 (95% CI: 0.42-0.76), and similar trends were found in ICS inhalation subgroup and ICS intratracheal instillation subgroup, with the corresponding RR being 0.58 (95% CI: 0.41-0.82) and 0.47 (95% CI: 0.24-0.95) respectively. ICS could also significantly reduce the mortality risk as compared with placebo control group (RR: 0.67;95% CI: 0.45-0.99), with RR of ICS inhalation subgroup and ICS intratracheal instillation subgroup being 0.81 (95% CI: 0.34-1.94) and 0.64 (95% CI: 0.41-0.99) respectively. Moreover, the percentage of infants using PS more than one time was lower in ICS group than in the placebo control group, with the RR and 95% CI being 0.55 (95% CI: 0.45-0.67), and that in ICS intratracheal instillation subgroup lower than in ICS inhalation subgroup (RR: 0.56;95% CI: 0.45-0.69, and RR: 0.35;95% CI:0.08-1.52 respectively). There was no significant difference in the incidence of infection or retinopathy of prematurity and neuro-motor system impairment between ICS group and placebo control group, with the corresponding RR being 0.95 (95% CI:0.59-1.52), 0.92 (95% CI: 0.62-1.38) and 1.13 (95% CI: 0.92-1.39), respectively. It was concluded that early administration of ICS and PS is an effective and safe option for preterm infants with NRDS in preventing BPD and reducing mortality, decreasing the additional PS usage, especially for the ICS intratracheal instillation subgroup. Furthermore, the appropriate dose and duration of ICS, combined use of inhalation or instillation of ICS with PS and the long-term safety of airway administration of corticosteroids need to be assessed in large trials.

Pulmonary hypertension and metabolic syndrome: Possible connection, PPARγ and Caveolin-1

A number of disparate diseases can lead to pulmonary hypertension(PH), a serious disorder with a high morbidity and mortality rate. Recent studies suggest that the associated metabolic dysregulation may be an important factor adversely impacting the prognosis of PH. Furthermore, metabolic syndrome is associated with vascular diseases including PH. Inflammation plays a significant role both in PH and metabolic syndrome. Adipose tissue modulates lipid and glucose metabolism, and also produces pro-and anti-inflammatory adipokines that modulate vascular function and angiogenesis, suggesting a close functional relationship between the adipose tissue and the vasculature. Both caveolin-1, a cell membrane scaffolding protein and peroxisome proliferator-activated receptor(PPAR) γ, a ligandactivated transcription factor are abundantly expressed in the endothelial cells and adipocytes. Both caveolin-1 and PPARγ modulate proliferative and anti-apoptotic pathways, cell migration, inflammation, vascular homeostasis, and participate in lipid transport, triacylglyceride synthesis and glucose metabolism. Caveolin-1 and PPARγ regulate the production of adipokines and in turn are modulated by them. This review article summarizes the roles and inter-relationships of caveolin-1,PPARγ and adipokines in PH and metabolic syndrome.

Surfactant Protein A Polymorphism Is Associated with Susceptibility to Chronic Obstructive Pulmonary Disease (COPD) in Chinese Uighur Population

This study investigatedexamined the correlation between surfactant protein-A (SP-A) polymorphism and the susceptibility of cvhronic obstructive pulmonary disease (COPD) in Xinjiang Uighurs. Genomic DNA was extracted from peripheral blood of 194 COPD smokers and 201 healthy smokers of Uighur who were hospitalized in or paid a visit to one of the four Xingjiang-based hospi-tals involved in the study, betweenfrom March 2009 to December 2010. Single nucleotide polymor-phisms (SNPs) were studied on A/G atwithin amino acid aa62 (CCA/CCG rs1136451) and C/T within aa219 (CGG/TGG, rs4253527) in SP-A. Genotypes were determined by using the TaqMan polymerase chain reaction (PCR). Our results showed that genotype frequencies were different be-tween the COPD and normal smokers infor aa62 (χx2=6.852, P=0.033). There were also significant differences in allele genotype frequencies between the COPD and the control and allele G might de-crease the risk COPD (χx2=6.545, P=0.011; OR=0.663; 95% CI: 0.484–0.909). The result suggested We were led to conclude that polymorphism of aa62 (CCA/CCG, rs1136451) of SP-A may be asso-ciated with the susceptibility to COPD in Xingjiang Uighurs.

Metabolic and genetic assessments interpret unexplained aggressive pulmonary hypertension induced by methylmalonic acidemia:A case report

BACKGROUND Pulmonary hypertension (PH) causes significant morbidity and mortality in diverse childhood diseases.However,limited information has been reported to obtain a good understanding of pediatric PH.Gaps exist between genome sequencing and metabolic assessments and lead to misinterpretations of the complicated symptoms of PH.Here,we report a rare case of a patient who presented with severe PH as the first manifestation without significant cardiovascular malformation and was finally diagnosed with methylmalonic aciduria (MMA) after metabolic and genomic assessments.CASE SUMMARY An 11-year-old female presented with an aggressive reduction in activity capability and shortness of breath for only 4 mo and suffered from unexplained PH.A series of examinations was performed to evaluate any possible malformations or abnormalities of the cardiovascular system and lungs,but negative results were obtained.The blood tests were normal except for manifestations of microcytic anemia and elevated total homocysteine.Computed tomography and magnetic resonance imaging failed to identify any pulmonary diseases.Cardiac catheterization examination identified a small right coronary artery to pulmonary artery shunt and severe PH.During the follow-up,PH progressed rapidly.Then,genome sequencing and metabolic disorder screening were performed,which confirmed a diagnosis of MMA with MMACHC c.80A>G/c and 609G> A mutations.Vitamin B12,betaine and bosentan were then administered as the main treatments.During the 6-mo follow-up,the pulmonary artery pressure dropped to 45 mmHg,while the right ventricle structure recovered.The patient’s heart function recovered to NYHA class Ⅱ.Metabolic disorder analysis failed to identify significant abnormalities.CONCLUSION As emerging types of metabolic dysfunction have been shown to present as the first manifestation of PH,and taking advantage of next generation sequencing technology,genome sequencing and metabolic disorder screening are recommended to have a more superior role when attempting to understand unclear or aggressive PH.

Expression of Peroxiredoxins and Pulmonary Surfactant Protein A Induced by Silica in Rat Lung Tissue

Silicosis is one of the most serious occupational diseases in China and dates back to centuries ago. In this study, we successfully established a rat model of silicosis by intratracheal silica injection for 28 days and determined hydroxyproline levels to evaluate collagen metabolism in lung homogenates. Oxidative stress status was evaluated by detecting catalase and glutathione peroxidase activities.

Vascular Metabolic Mechanisms of Pulmonary Hypertension

Pulmonary hypertension(PH)is a severe and progressive disease characterized by increased pulmonary vascular resistance leading to right heart failure and death.In PH,the cellular metabolisms including those of the three major nutrients(carbohydrate,lipid and protein)are aberrant in pulmonary vascular cells.Glucose uptake,glycolysis,insulin resistance,sphingolipid S1P,PGE2,TXA2,leukotrienes and glutaminolysis are upregulated,and phospholipid-prostacyclin and L-arginine-nitric oxide pathway are compromised in lung vascular cells.Fatty acid metabolism is disordered in lung endothelial cells and smooth muscle cells.These molecular mechanisms are integrated to promote PH-specific abnormal vascular cell proliferation and vascular remodeling.This review summarizes the recent advances in the metabolic reprogramming of glucose,fatty acid,and amino acid metabolism in pulmonary vascular remodeling in PH and the mechanisms for how these alterations affect vascular cell fate and impact the course of PH.

Effect of different ventilation methods combined with pulmonary surfactant on neonatal acute respiratory distress syndrome

BACKGROUND Acute respiratory distress syndrome precipitates is widespread pulmonary injury in impacted individuals,the neonatal respiratory distress syndrome(NRDS),primarily observed in preterm infants,represents a prevalent critical condition in neonatal clinical settings.AIM To investigate the clinical efficacy of various ventilation strategies combined with pulmonary surfactant(PS)therapy in the treatment of NRDS.METHODS A total of 20 neonates diagnosed with respiratory distress syndrome,admitted between May 2021 and June 2022,were randomly assigned to either a research group or a control group.Neonates in the research group received treatment involving high-frequency oscillatory ventilation(HFOV)in conjunction with PS.In contrast,neonates in the control group were administered either controlled mechanical ventilation or synchronous intermittent mandatory ventilation,combined with PS.Arterial blood samples from the neonates in both groups were collected before treatment,as well as 6 h,12 h,24 h,and 48 h post-treatment.These samples underwent blood gas analysis,with measurements taken for pH value,partial pressures of oxygen(O_(2))and carbon dioxide.Concurrently,data was collected on the duration of ventilator use,length of hospitalization time,O_(2) treatment time,treatment outcomes,and complications of the ventilator.RESULTS From 6-48 h post-treatment,both groups demonstrated significant improvements in arterial blood pH and oxygen partial pressure,along with a significant decrease in carbon dioxide partial pressure compared to pre-treatment values(P<0.05).Although these changes progressed over time,there were no significant differences between the two groups(P>0.05).However,the research group had significantly lower X-ray scores,shorter hospitalization time,and less time on O_(2) therapy compared to the control group(P<0.05).Mortality rates were similar between the two groups(P>0.05),but the research group had a significantly lower incidence of complications(P<0.05).CONCLUSION The integration of HFOV combine with PS has proven to effectively expedite the treatment duration,decrease the occurrence of complications,and secure the therapeutic efficacy in managing NRDS.

Functional changes of pulmonary surfactant in rats with lung injury induced by endotoxin

We studied the functional changes of pulmonary surfactant （PS） in acutelung injury models produced by endotoxin injection (E.coli O55B5) in rats.The sur-face properties of the lung lavage liquid and the total phospholipids （TPL） ex-tracted from it were assessed on a modified Wilhelmy film balance.γ-A isothermof the lavage liquid revealed an increase in minimum surface tension and a de-crease in hysteresis area,recruitment index and stability index,whereas that ofTPL extracted from it did not show any change except for hysteresis area.Thesurface activity correlates positively with the TPL content but negatively with thetotal protein content in the lavage liquid.The findings indicated that there was adysfunction of PS in rats with the lung injury induced by endotoxin,suggestingthat the function deficiency of PS might be caused by decreased phospholipidsand increased proteins in the alveoli.

Intervention effect of Danbei Yifei formula on pulmonary fibrosis based on urine metabolomics by UHPLC-Q-Exactive

Objective:Determine the urinary biomarkers and pathogenesis of pulmonary fibrosis rats,and elaborate the intervention mechanism of DanBei YiFei formula.Methods:Bleomycin was injected into the trachea to induce pulmonary fibrosis in rats after anesthesia,and the diagnostic indexes of clinical pulmonary fibrosis,including superoxide dismutase,glutathione and malondialdehyde,were measured.High-throughput metabolic data of rats with pulmonary fibrosis were obtained by the latest high-resolution liquid-mass spectrometry technology,the multidimensional data were processed by Chemometrics algorithm to screen biomarkers related to pulmonary fibrosis.While,metabolic function indexes of rats after administration was observed,and the effective mechanism of DanBei YiFei formula on pulmonary fibrosis was expounded.Results:The clinical biochemical indexes showed that there were significant differences in metabolism in the model group,which confirmed the success of the preparation of the model of pulmonary fibrosis.Metabolisms research showed that the metabolic contour of the rats with pulmonary fibrosis was found to be significantly deviated,and the metabolism in vivo was abnormal.After the DanBei YiFei formula was given,the overall metabolic contour of the rats showed a trend of back modulation,and developed in the direction of healthy rats.With database matching and data processing 12 biomarkers,including Fumaric acid,Arginine and Spermidine,were obtained which were radically different from those of healthy rats and pulmonary fibrosis rats.Conclusion:DanBei YiFei formula has definite therapeutic effect on pulmonary fibrosis rats.Regulation of Tricarboxylic acid cycle and Arginine metabolic pathway may be the mechanism of its treatment of pulmonary fibrosis.

Morphofunctional Characteristics of Pulmonary Surfactant System and Its Effect on Immune Cells in Influenza A (H1N1) Pathogenesis

There is an annual increase of influenza-related SARI cases in winter months. Despite the high relevance of this problem, influenza pathogenesis and the role of surfactant system and its SP-A (surfactant protein A) enzyme in antiviral defense remain poorly understood. SP-A activates macrophage M1 polarization and triggers an antiviral response due to the activation of T-cells and dendritic cells. Therefore, surfactant system is an important element of infection protection and a promising therapeutic target.

Correlation of neonatal pulmonary surfactant protein A gene polymorphism with pneumonia susceptibility and inflammatory response

Objective:To study the correlation of neonatal pulmonary surfactant protein A gene polymorphism with pneumonia susceptibility and inflammatory response.Methods:Neonates who were born and diagnosed with pneumonia in Zigong Maternity and Child Healthcare Hospital between September 2015 and February 2017 were selected as pneumonia group, and neonates without infection were selected as control group. SP-A gene rs1059054 and rs1136454 loci polymorphism, the contents of inflammatory cytokines in serum as well as the expression of inflammatory transcription factors in peripheral blood were determined.Results:The constituent ratio of rs1059054 loci CC genotype of pneumonia group was significantly higher than that of control group while the constituent ratio of CT and TT genotypes were significantly lower than those of control group;the constituent ratio of rs1136454 loci AA genotype was significantly lower than that of control group while the constituent ratio of AG and GG genotypes were significantly higher than those of control group. PCT, sTREM1, TNF-α and IL-6 levels in serum as well as RORγt mRNA expression in peripheral blood of pneumonia children with SP-A gene rs1059054 loci CC genotype were significantly higher than those of pneumonia children with CT genotype and TT genotype while SOCS1 and Foxp3 mRNA expression in peripheral blood were significantly lower than those of pneumonia children with CT genotype and TT genotype;PCT, sTREM1, TNF-α and IL-6 levels in serum as well as RORγt mRNA expression in peripheral blood of pneumonia children with SP-A gene rs1136454 loci AA genotype were significantly lower than those of pneumonia children with AG genotype and GG genotype while SOCS1 and Foxp3 mRNA expression in peripheral blood were significantly higher than those of pneumonia children with AG genotype and GG genotype.Conclusion: Neonatal SP-A gene rs1059054 loci CC genotype can increase the pneumonia susceptibility and aggravate inflammatory response, and rs1136454 loci AA genotype can decrease pneumonia susceptibility and relieve inflammatory response.

Study on Pulmonary Surfactant of Sudden Death of Infant

Objective To find the pathogenesis of sudden infant death syndrome (SIDS) from changes of pulmonary surfactant. Methods By means of thin layer chromatography technique, surfactant in whole lung specimens of 10 infants with SIDS and 10 control infants without SIDS (dead of nonrespiratory diseases) were examined qualitatively and quantitatively. Results Eleven components in pulmonary surfactant were examined qualitatively, including lysophosphatidylcholine, sphingomyelin, phosphatidylcholine, phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidic acid, cholesterol and neutral lipids. Quantitative examination showed that the amount of surfactant of whole lung specimens in sudden death group [(8.9±1.0) mg/g wet lung weight] was significantly less than that in control group [(12.6±1.4) mg/g wet lung weight, P<0.01]. Qualitative variance showed that the percentages of phosphatidylcholine (49.4%±2.0%) and phosphatidylglycerol (2.6%±0.7%) decreased markedly in sudden death group compared with those in control group (61.5%±3.0% and 4.3%±1.5%, P<0.01). Conclusion Before death there is serious defect on metabolism of pulmonary surfactant in sudden death infants, with the amount decreasing and the ratio of its components being disturbed, which is one of the important pathogenies of SIDS.

Effects of Different Surfactant Administrations on Cerebral Autoregulation in Preterm Infants with Respiratory Distress Syndrome

To treat respiratory distress syndrome,surfactant is currently delivered via less invasive surfactant administration（LISA） or INtubation SURfactant Extubation（INSURE）.The aim of this study was to compare the effect of the two delivery methods of surfactant on cerebral autoregulation.Near infrared spectroscopy monitoring was carried out to detect cerebral oxygen saturation（Sc O2）,and the mean arterial blood pressure（MABP） was simultaneously recorded.Of 44 preterm infants included,the surfactant was administrated to 22 via LISA and 22 via INSURE.The clinical characteristics,treatments and outcomes of the infants showed no significant differences between the two groups.The correlation coefficient of Sc O2 and MABP（rSc O2-MABP） 5 min before administration was similar in the two groups.During surfactant administration,rSc O2-MABP increased in both groups（0.44±0.10 to 0.54±0.12 in LISA,0.45±0.11 to 0.69±0.09 in INSURE）.In the first and second 5 min after instillation,rSc O2-MABP was not significantly different from baseline in the LISA group,but increased in the first 5 min after instillation（0.59±0.13,P=0.000 compared with the baseline in the same group） and recovered in the second 5 min after instillation（0.48±0.10,P=0.321） in the INSURE group.There were significant differences in the change rates of rSc O2-MABP between the two groups during and after surfactant administration.Our results suggest that cerebral autoregulation may be affected transiently by surfactant administration.The effect duration of LISA is shorter than that of INSURE（〈5 min in LISA vs.5–10 min in INSURE）.

Implication of proliferation gene biomarkers in pulmonary hypertension

Objective/Background:Proliferation is a widely recognized trigger for pulmonary hypertension(PH),a life-threatening,progressive disorder of pulmonary blood vessels.This study was aimed to identify some proliferation associated genes/targets for better comprehension of PH pathogenesis.Methods:Human pulmonary arterial smooth muscle cells(hPASMCs)were cultured in the presence or absence of human recombinant platelet derived growth factor(rhPDGF)-BB.Cells were collected for metabolomics or transcriptomics study.Gene profiling of lungs of PH rats after hypoxia exposure or of PH patients were retrieved from GEO database.Results:90 metabolites(VIP score>1,fold change>2 or<0.5 and p<.05)and 2701 unique metabolism associated genes(MAGs)were identified in rhPDGF-BB treated hPASMCs compared to control cells.In addition,1151 differentially expressed genes(313 upregulated and 838 downregulated)were identified in rhPDGF-BB treated hPASMCs compared to control cells(fold change>2 or<0.5 and p<.05).152 differentially expressed MAGs were then determined,out of which 9 hub genes(IL6,CXCL8,CCL2,CXCR4,CCND1,PLAUR,PLAU,HBEGF and F3)were defined as core proliferation associated hub genes in protein proten interaction analysis.In addition,the hub gene-based LASSO model can predict the occurrence of PH(AUC=0.88).The expression of CXCR4,as one of the hub genes,was positively correlated to immune cell infiltrates.Conclusion:Our findings revealed some key proliferation associated genes in PH,which provide the crucial information concerning complex metabolic reprogramming and inflammatory modulation in response to proliferation signals and might offer therapeutic gains for PH.

Changes of Tumor Necrosis Factor, Surfactant Protein A, and Phospholipids in Bronchoalveolar Lavage Fluid in the Development and Progression of Coal Workers’ Pneumoconiosis

Objective To evaluate the alterations of biomarkers in the development and progression of coal workers＇ pneumoconiosis （CWP）. Methods The type and number of cells, and the levels of tumor necrosis factor-alpha （TNF-α）, pulmonary surfactant protein, phospholipids and fibronectin in bronchoalveolar lavage fluid were assayed in 14 health active coal miners, 21 coal miners without CWP and 13 miners with CWP of 0/1 to 1/1. Results Compared to active coal miners without CWP （8,23μg/mL）, TNF-α concentration was gradually decreased when dust exposure was stopped （5.90 μg/mL）. Elevated surfactant protein A （SP-A） level and phosphatidylglycerol （PG） to phosphatidylinositol （PI） ratio were found in miners actively exposed to coal dust （6528 μg/mL for SP-A and 10. for PG/P1）, and both parameters decreased when CWP progressed from CWP （0/1） （3419μg/mL for SP-A and 5.9 for PG/PI） to CWP （1/1） （1654 μg/mL for SP-A and 5.5 for PG/PI）. Conclusion Biomarkers in bronchoalveolar lavage fluid can be used to screen coal miners at high risk of developing coal workers＇ pneumoconiosis.