Relationship between plasma SP-A expression level and disease stage in silicosis patients / 上海预防医学

ObjectiveTo investigate the relationship between plasma surfactant protein⁃A （SP⁃A） expression level and silicosis progression， and to provide early evidence for exploring whether SP⁃A can be used as a biomarker for clinical monitoring of silicosis disease progression. MethodsWe recruited 187 silicosis patients in Guangdong Province hospital for occupational disease prevention and treatment between November， 2019 and November，2020. Their peripheral venous blood samples were collected for the plasma isolation. The level of pulmonary SP⁃A was detected by enzyme-linked immunosorbent assay. ResultsThere was a statistically significant difference in the level of SP⁃A among the silicosis groups （P<0.05）， and the plasma SP-A level of the silicosis patients in stage Ⅲ was higher than that in stage Ⅰ and stage Ⅱ （P<0.05）. Smoking had effect on plasma SP⁃A levels， Age， working years and drinking had no effect on plasma SP⁃A levels. ConclusionThe expression level of SP⁃A in the plasma of silicosis patients is increased， which has a certain correlation with the disease stage， and plays a certain early warning role in the occurrence and development of silicosis， and may be a potential biomarker for the diagnosis and prognosis of silicosis.

Dynamic changes and clinical value of serum angiopoietin-2 and surfactant protein D in pediatric acute respiratory distress syndrome / 中国小儿急救医学

Objective:To study the relationship between the dynamic changes of angiopoietin-2 (Ang-2) and surfactant protein D (SP-D) in pediatric acute respiratory distress syndrome (pARDS) and the severity and prognosis of the disease.Methods:Using nested case-control study method, 80 children with pneumonia complicated with pARDS admitted to PICU at Fujian Maternal and Child Health Hospital from June 2018 to May 2021 were selected as pARDS group, and 19 healthy children with corresponding age were selected as control group.According to the oxygenation, the children in pARDS group were divided into three subgroups: mild group (23 cases), moderate group (32 cases) and severe group (25 cases). According to the prognosis at discharge, the children in pARDS group were divided into survival group (67 cases) and death group (13 cases). Ang-2 and SP-D were detected by enzyme-linked immunosorbent assay.The levels of Ang-2 and SP-D in children with pARDS of different severity on the first day were compared; The changes of Ang-2 and SP-D levels on the 1st, 3rd and 8th day of children in survival group and death group were compared, and the receiver operating characteristic (ROC) curve was plotted to compare the predictive value of Ang-2 and SP-D for pARDS prognosis.Results:(1) The levels of Ang-2 and SP-D on the first day in pARDS group were significantly higher than those in control group( P<0.001). (2) The levels of Ang-2 and SP-D on the first day in children with pARDS of different severity levels were significantly different ( P<0.001), and the levels of Ang-2 and SP-D increased gradually with the increase of disease severity.(3) The levels of Ang-2 and SP-D in death group were significantly higher than those in survival group on the 1st, 3rd and 8th day ( P<0.05). (4) Prognostic efficacy of Ang-2 and SP-D levels in pARDS group at different time points: when the areas under the ROC curve predicted by Ang-2 on the 1st, 3rd and 8th day for inpatient mortality in children with pARDS were 0.808, 0.981 and 0.989, respectively; the optimal cut-off values were 6 000 pg/mL, 6 971 pg/mL and 4 171 pg/mL, respectively; the sensitivity was 84.6%, 92.3% and 92.3%, respectively; and the specificity was 76.1%, 97.0% and 98.5%, respectively.The areas under the ROC curve predicted by SP-D on the 1st, 3rd and 8th day for inpatient mortality in children with pARDS were 0.689, 0.993 and 0.983, respectively; the optimal cut-off values were 13544 pg/mL, 16003 pg/mL and 12294 pg/mL, respectively; the sensitivity was 84.6%, 100.0% and 100.0%, respectively; and the specificity was 46.3%, 98.5% and 97.0%, respectively. Conclusion:Serum Ang-2 and SP-D levels in children with pARDS increase with the aggravation of the disease.The dynamic changes of Ang-2 and SP-D in children with pARDS with different prognosis are different during the course of disease, and monitoring serum Ang-2 and SP-D during the course of disease has a certain predictive value for clinical outcome.

The role of surfactant associated protein-A in silicosis / 中国职业医学

Objective: To investigate the role of surfactant associated protein-A (SP-A) in the development and progression of silicosis, and its mechanism. Methods: Homozygous and heterozygous mice of SP-A knockout of specific pathogen free (SPF) grade were selected for mating, and mice with SP-A-/- genotype were selected for subsequent experiments. SP-A wild-type (SP-A+/+) and SP-A-/- mice were divided into SP-A+/+ control group, SP-A-/- control group, SP-A+/+ silicosis group and SP-A-/- silicosis group with six mice in each group by random number table method. Mice in both silicosis groups were given 20.0 μL 250 g/L silica suspension by tracheal exposure, and mice in both control groups were injected with 0.9% sodium chloride solution at the same volume. On the 28th day after modeling, mice were sacrificed. Lung tissues were used for lung histopathology examination. The apoptosis of alveolar type Ⅱ epithelial cells of mice was detected by TUNEL method. The mRNA expression of B-lymphoblastoma 2 (Bcl-2), Bcl-2 associated X protein (Bax), cysteinyl aspartate specific proteinase (Caspase)-3 and Caspase-9 in lung tissues of mice was detected by quantitative real-time polymerase chain reaction. Results: The histopathological result of mice showed that thickened alveolar septum, scattered silicon nodule and collagen fiber formation were observed in the mice lungs of SP-A+/+ silicosis group, and a large number of inflammatory cells were observed in silicosis nodule, after exposure to silica dust. SP-A-/- silicosis group resulted in a more severe pulmonary inflammation and interstitial fibrosis compared to SP-A+/+ silicosis group. The apoptosis of alveolar type Ⅱ epithelial cells and the mRNA relative expression levels of Bax, Caspase-3 and Caspase-9 in lung tissues of mice in each silicosis groups were increased compared with their control groups (all P<0.05). The above four indexes of mice in SP-A-/- silicosis group were higher than those in SP-A+/+ silicosis group (all P<0.05). There was no significant difference in the expression of Bcl-2 mRNA in lung tissues of these four groups (P>0.05). Conclusion: Knockout of SP-A can aggravate inflammation and pulmonary fibrosis in silicosis model mice, and promote apoptosis of alveolar type Ⅱ epithelial cells. The mechanism may be related to the Bcl-2/Bax/Caspase-3 signaling pathway which affects the apoptosis of mitochondrial pathway.

Serum MMP-9, SP-D, and VEGF levels reflect the severity of connective tissue disease-associated interstitial lung diseases

Abstract Background: Interstitial lung disease (ILD) is a common pulmonary complication of connective tissue disease (CTD). This study aims to evaluate the clinical diagnostic value of matrix metalloproteinase-9 (MMP-9), surfactant protein-D (SP-D), and vascular endothelial growth factor (VEGF) as potential biomarkers for CTD-ILD. Methods: This research included 33 CTD-ILD patients, 31 CTD patients without ILD, and 24 healthy control subjects. Then, the value of biomarkers for the diagnosis and evaluation of CTD-ILD was assessed through high-resolution computed tomography (HRCT) findings and pulmonary function test (PFT) parameters. Results: The serum MMP-9, SP-D, and VEGF levels in the CTD-ILD group were higher than those in the CTD-NILD group and healthy group. The ROC curve indicates that VEGF has good to excellent diagnostic performance in diagnosing CTD-ILD, the cut-off that best optimizes sensitivity and specificity in diagnosing CTD-ILD is 277.60 pg/ml (sensitivity, 87.9%; specificity, 83.6%), with an area under the curve (AUC) of 0.905 (95% confidence interval (CI) 0.842-0.968); The ROC curve for MMP-9 suggests this biomarker is fair for diagnosis of CTD-ILD(sensitivity, 81.8%; specificity, 81.8%), with an AUC of 0.867 (95% CI 0.784-0.950), but SP-D only provided lower specificity with higher sensitivity in diagnosing CTD-ILD(sensitivity, 90.9%; specificity, 40.0%). The different serum biomarkers are more specific and sensitive when combined to diagnose ILD. The semiquantitative score for the degree of ILD severity on HRCT was positively correlated with SP-D and VEGF levels ( r = 0.461, P = 0.007; r = 0.362, P = 0.039), and serum MMP-9 levels were elevated in the UIP subgroup compared to the non-UIP subgroup. The percentage of diffusing capacity of the lung for carbon monoxide (DLco) (% predicted) had a negative correlation with the SP-D level ( r = − 0.407, P = 0.044) and a statistically negative correlation between MMP-9 and the forced vital capacity (FVC) ( r = − 0.451, P = 0.024). Conclusions: Serum MMP-9, SP-D, and VEGF levels may have clinical value in screening and evaluating the severity of CTD-ILD. Key points Serum MMP-9, SP-D, and VEGF levels were increased in patients with CTD-ILD and they may have clinical value in screening and evaluating the severity of CTD-ILD. Serum SP-D and VEGF levels had a positive correlation with ILD severity as measured using semiquantitative HRCT scores. Serum MMP-9 levels were elevated in the UIP subgroup compared to the non-UIP subgroup. Therefore, further research is required to determine the role of serum MMP-9 levels in the preliminary determination of the ILD subtype. Serum MMP-9 levels had a negative correlation with DLco, and serum SP-D levels had a negative correlation with FVC.

Effect of acute exposure to electronic cigarette on bronchoalveolar lavage fluid and pulmonary surfactant protein in mice / 预防医学

Objective@#To assess the effects of acute exposure to electronic cigarette ( e-cigarette ) on leukocyte and total protein levels in bronchoalveolar lavage fluid ( BALF ) and pulmonary surfactant protein expression in a mouse model, so as to provide insights into the elucidation of the mechanism underlying the damages to the respiratory system caused by e-cigarette.@*Methods@#Twenty-one C57BL/6N female mice were randomly divided into the blank control group, the solvent control group and the nicotine group. Mice in the solvent control group and the nicotine group were exposed to the solvent aerosol or e-cigarette aerosol containing 25 mg/mL nicotine for 3 hours daily, while mice in the blank control group were bred in clean air. Following 3-day exposure, mouse BALF and lung specimens were collected. The cell morphology was observed using microscopy following Wright-Giemsa staining and the leukocyte count was estimated in BALF, while the total protein expression was quantified using bicinchoninic acid ( BCA ) assay. In addition, the mRNA expression of pulmonary surfactant protein genes was detected in mouse lung specimens using quantitative real-time PCR ( qPCR ) assay.@*Results@#All mice in three groups grew well without obvious abnormality or death seen. Wright-Giemsa staining showed a higher number of mononuclear macrophages in mouse BALF in the nicotine group than in the blank control group and the solvent control group. The leukocyte counts were ( 2.00±0.77 )×107, ( 1.79±0.99 )×107 and ( 4.00±1.35 )×107 cells/L ( F=9.199, P=0.002 ), and the total protein levels were ( 0.16±0.03 ), ( 0.12±0.02 ) and ( 0.16±0.04 ) mg/mL in mouse BALF in the blank control group, solvent control group and nicotine group ( F=3.610, P=0.048 ), and the relative mRNA expression of pulmonary surfactant protein B (SP-B) and SP-D was 1.00±0.14, 0.82±0.12 and 0.74±0.07 ( F=5.491, P=0.028 ), and 1.00±0.06, 0.90±0.02 and 0.71±0.15 in mouse lung specimens, respectively ( F=10.460, P=0.005 ). The leukocyte count was significantly higher in the nicotine group than in the blank control group and solvent control group (P=0.007, 0.003), and the total protein content was higher in the nicotine group than in the solvent control group ( P=0.060 ), while the relative SP-B mRNA expression was lower in the nicotine group than in the blank control group ( P=0.025 ), and the relative SP-D mRNA expression was lower in the nicotine group than in the blank control group and solvent control group ( P=0.004, 0.041 ).@*Conclusion@#Acute exposure to e-cigarette results in elevated intrapulmonary inflammatory responses, pulmonary capillary barrier impairment and reduced pulmonary surfactant protein expression.

Research progress on the role of surfactant protein A and D in pulmonary fibrosis / 中国职业医学

Pulmonary fibrosis is an interstitial lung disease caused by different pathogenic factors. It has the characteristics of high morbidity and poor prognosis, which seriously affects the quality of life of patients. However, its pathogenesis has not yet been fully elucidated. Surfactant protein(SP)-A and SP-D are lipoprotein complexes distributed at the air-liquid interface of alveoli, synthesized and secreted by alveolar type Ⅱ epithelial cells and bronchiolar cells. They are important parts of the innate immune system, which participate in the host defense process through a variety of regulatory methods, and play an important role in regulating cell apoptosis and lung inflammation, promoting the process of epithelial repair and maintaining the stability of alveolar structure. The disorder and mutation of SP-A and SP-D may be the influencing factors of the pathogenesis of pulmonary fibrosis. Serum SP-A and SP-D levels are differentially expressed in patients with pulmonary fibrosis and normal healthy individuals, and are related to the severity of pulmonary fibrosis. They are considered to be a class of biomarkers that sensitively reflect lung epithelial cell damage and can be used in the diagnosis, treatment and prognostic evaluation of pulmonary fibrosis.

Clinical significance of Clara cell secreted protein 16 and pulmonary surfactant protein-A in early diagnosis of neonatal acute respiratory distress syndrome / 中国小儿急救医学

Objective:To investigate the clinical significance of changes of serum Clara cell secretory protein(CC16) and pulmonary surfactant protein A(SP-A) in neonates with acute respiratory distress syndrome(ARDS).Methods:The data of 30 neonates with ARDS who needed mechanical ventilation in neonatal intensive care unit of Xi′an Children′s Hospital from January 2016 to November 2018 were collected as observation group, including 12 cases in mild group, 10 cases in moderate group and 8 cases in severe group.The data of healthy newborns during the same period were taken as control group.The serum levels of CC16 and SP-A were detected by ELISA.The serum levels of CC16 and SP-A among different groups were compared.Results:The levels of serum CC16 and SP-A in ARDS group were (59.35±3.67)mg/L and(75.38±6.27)mg/L respectively, (11.26±1.32)mg/L and(18.15±2.69)mg/L in healthy group.The difference was significant( P<0.05). And the differences of serum CC16 and SP-A levels among different degree ARDS groups were significant( P<0.05). The levels of serum CC16 in mild, moderate and severe subgroup were(38.27±16.01)mg/L, (51.25±15.63)mg/L, (84.76±13.12)mg/L and SP-A were(47.02±7.18)mg/L, (73.12±7.98)mg/L, (96.45±12.50)mg/L, which increased with disease severity. Conclusion:Serum CC16 and SP-A are increased and correlated with the severity of neonatal ARDS, which may be used as the index for evaluating the severity of neonatal ARDS in the future.

Analysis of the pedigree of a child with interstitial lung disease caused by a novel mutation of p. K114N in SFTPC gene / 中国小儿急救医学

Objective:To analyze the clinical and chest CT features in a family with interstitial lung disease(ILD), and assess the probable causative gene mutations for the family.Methods:In order to identify the etiology of the proband′s ILD, the pedigree was investigated.The clinical data of five proband′s pedigree members were collected, and the chest HRCT examination was performed on four proband′s pedigree members with respiratory symptoms.The human whole exon sequencing was performed on the proband′s blood samples, then its deleterious effects were assessed.Subsequently, the strong pathogenic mutation was validated by Sanger sequencing.Results:According to the family survey, there were five patients with ILD in the family, including three males and two females.One of them died.The surfactant protein C(SFTPC)gene(exon4, c.342G>T, p.K114N)was found in all four surviving patients.The mutation was considered to be originated from the father of the proband, and the pathogenic mutation was considered, which was not included in the databases and was a noval mutation.In addition, the clinical manifestations of different patients in the family were significantly different.Conclusion:The novel mutation of p. k114n in SFTPC gene can lead to ILD in children, and the mutation has incomplete exons in family members.Chest CT and whole exon sequencing play an important role in the diagnosis of ILD in children.

Role of surfactant proteins in viral keratitis / 国际眼科杂志(Guoji Yanke Zazhi)

@#Innate immunity plays an important role in viral keratitis. Recently, it has been found that surfactant proteins(SP)A and D in the innate immune system are essential in viral keratitis. SP can inhibit virus adhesion to host cells and further promote phagocytosis of virus through high affinity for virus ligands. In order to ensure the normal function of tissues in the early stage of virus infection, SP regulates immune cells to maintain a non-inflammatory state. However, when pathogen invasion increases, SP promoted inflammation and increased the immune cells to kill the pathogens. SP-A and SP-D could be expressed in cornea, conjunctiva. To play the role of anti-adenovirus, herpes simplex virus, cytomegalovirus and other major eye pathogenic viruses, SP-A and SP-D combine with the virus to prevent entry into cells, promote phagocytosis, and directly kill the virus. SP-A and SP-D may be used as clinical diagnostic tools for viral infection. In the future, recombinant SP is expected to be used as an important means for the treatment of viral keratitis. Here, we review the innate immune function of SP-A and SP-D in ocular viral infection.

Progress in surfactant protein D-involved immune inflammatory responses / 中华微生物学和免疫学杂志

Surfactant protein D ( SP-D) is an important component of the surfactant family and ex-pressed in lung as well as many other organs. SP-D is a natural immune protein, which plays an important role in immune defense in lung tissues and in the regulation of inflammatory responses. Moreover, it also participates in immune inflammatory responses in other organs. This paper reviewed the function of SP-D in the regulation of immune inflammatory responses and its regulatory mechanisms in common diseases, and summarized the prospect of SP-D in disease treatment.

Progress on PM2.5 and its adverse impact on lung tissues / 中华实用儿科临床杂志

The atmospheric particulate matter(PM) is widely regarded as one of major environmentally and unfriendly ambient air pollution,and therein PM2.5 (diameter≤2.5 μm) is most closely related to human health.Because of its smaller diameter with longer suspension duration,PM can absorb many pathogenic microorganisms,and easily enter into the deep of airway and then deposit on the bronchus and alveoli,and it brings damage to the lung tissues and the surfactant proteins.PM can give rise to oxidative stress,inflammation response,cells and DNA damage.Now,this review focuses on the characterization and composition of PM,as well as the impact of PM2.5 on the lung,surfactant proteins and human health,which helps to call for more people to pay attention to this environmental issue in order to better mitigate and prevent the damage caused by PM.

Diagnostic value of lung injury biomarkers in neonatal acute respiratory distress syndrome / 国际儿科学杂志

Objective@#To investigate the role of E-selectin, Clara cell secretory protein 16 (CC-16), and pulmonary surfactant protein A (SP-A) in the diagnosis of neonatal ARDS.@*Methods@#Full-term newborn with ARDS in 9 hospitals of Jiangsu Province from March 1st 2015 to February 29th 2016 were selected as observation group.According to the lung oxygenation of the neonates, they were divided into three groups: mild, moderate and severe.In addition, 60 normal full-term newborns were selected as control group.In the observation group, venous blood samples were taken on the 1st, 3rd and 7th day of diagnosis and the control group within 7 days after birth.The level of E-selectin, CC-16 and SP-A were detected by double antibody sandwich enzyme-linked immunosorbent assay.The changes of the level of E-selectin, CC-16 and SP-A at different time points and in neonatus with different severity of ARDS were compare with control group and correlatively analyzed.@*Results@#The observation group included 60 newborns who met the diagnostic criteria of ARDS with male 38, female 22, day age (7.3 ±3.3) hours, gestational age (39.5 ±1.7) weeks and birth weight (3280 ±577) g. The control group included 60 normal full-term newborns, with male 30, female 30, day age (6.9 ±4.2) hours, gestational age (39.4 ±1.5) weeks and birth weight (3329 ±593) g. There was no significant difference between two groups.The levels of E-selectin[1 d, 3 d, 7 d: (36.36 ±8.32)μg/L, (45.51 ±9.26)μg/L, (57.15 ±6.84)μg/L], CC-16[1 d, 3 d, 7 d: (25.24 ±8.63)mg/L, (48.33±10.83)mg/L, (18.84±10.11)mg/L]and SP-A [1 d, 3 d, 7 d: (58.38±10.31)mg/L, (53.29±11.31)mg/L, (25.99±6.66)mg/L]in the blood of the observation group increased on the first day and reached the peak on the third day, which were significantly higher than those in the control group [E-selectin, CC-16, SP-A: (15.52 ±6.24)μg/L, (11.26 ±5.18)mg/L, (24.30 ±5.27)mg/L] (P<0.05). The levels of E-selectin [mild, moderate, severe are(30.07±6.10)μg/L, (33.39 ±6.64)μg/L, (41.63 ±7.36)μg/L], CC-16 [mild, moderate, severe are(12.61 ±5.80)mg/L, (25.22 ±6.77)mg/L, (30.61 ±4.69)mg/L]and SP-A [mild, moderate, severe are(49.67 ±8.26)mg/L, (7.11 ±7.94)mg/L, (63.19 ±11.45)mg/L]increased gradually in the blood of ARDS neonates with different severity (P<0.05), especially in moderate and severe degree.There was a significant negative correlation between E-selectin (r=-0.629 8), CC-16 (r=-0.679 3), SP-A (r=-0.458 8) and PaO2/FiO2 (P<0.05).@*Conclusion@#The levels of E-selectin, CC-16 and SP-A in the blood of ARDS neonates increased significantly and were closely related to the severity of the disease, which may be a biomarker of neonatal lung injury.

Progress on PM2.5 and its adverse impact on lung tissues / 中华实用儿科临床杂志

The atmospheric particulate matter(PM) is widely regarded as one of major environmentally and unfriendly ambient air pollution, and therein PM2.5 (diameter≤2.5 μm) is most closely related to human health.Because of its smaller diameter with longer suspension duration, PM can absorb many pathogenic microorganisms, and easily enter into the deep of airway and then deposit on the bronchus and alveoli, and it brings damage to the lung tissues and the surfactant proteins.PM can give rise to oxidative stress, inflammation response, cells and DNA damage.Now, this review focuses on the characterization and composition of PM, as well as the impact of PM2.5 on the lung, surfactant proteins and human health, which helps to call for more people to pay attention to this environmental issue in order to better mitigate and prevent the damage caused by PM.

Correlation between polymorphisms of surfactant protein A1 rs1059047 and rs1136450 and respiratory distress syndrome in Mongolian premature infants / 中华急诊医学杂志

Objective To study the correlation between polymorphisms of surfactant protein A1 rs1059047 and rs1136450 and respiratory distress syndrome (RDS) in Mongolian premature infants in Inner Mongolia.Methods Totally 50 Mongolian RDS premature infants in our ward were recruited as the case group (33 males and 17 females),and another 50 Mongolian non-RDS premature infants with same ethnicity,same sex and gestational age were served as the control group (29 males and 21 females).Single nucleotide polymorphisms of SP-A1 rs1059047 and,rs1136450 and allele haploids (6A,6A2,and 6A3) were detected by polymerase chain reaction-single strand conformation polymorphism gene detection technology and were compared between the case and control groups.Results Threegenotypes,CC,TT,CT were detected in the case and control groups at rs1059047,all ofwhich were mainly TT genotype.There was no significant difference in genotype frequency between the two groups (x2=1.429,P ＞ 0.05).Two genotypes,CG and GG,were detected in the case and control groups at rsl 136450,and CG was the dominant genotype.There was no significant difference in genotype frequency between the two groups (x2=1.624,P＞0.05).The distribution frequency of SP-A1 allele haploids (6A,6A2,6A3) in the case group was 36％,68％ and 42％,respectively,and 62％,46％ and 50％ in the control group,respectively.There was no significant differencein the frequency of allele haploid 6A3 between the two groups (x2=0.502,P＞0.05);but there was a significantly difference in the frequency of allele haploids (6A,6A2) between the two groups (x2=6.763,4.937,P＜0.05).Conclusions The alleles and allele fiequency of SP-A1 (rs1059047,rs1136450) were not associated with RDS in Mongolian premature infants.However,SP-A1 allele haploid 6A2 is the susceptible gene for RDS in Mongolian premature infants,and haploid 6A is the protective gene.

The role of erlotinib in the acute lung injury and the expression of surfactant protein A / 中华急诊医学杂志

Objective To investigate the role of erlotinib in the expression of surfactant protein A (SP-A) in LPS-induced acute lung injury (ALI) of mice model.Methods C57BL/6 mice were randomly (random number)divided into control group (n=6),ER group (n=6),LPS group (n=6),and ER+LPS group (n=6).In the LPS group,2 mg/kg LPS was instilled into trachea of mice to induce lung injury.In control group,normal saline was instilled into trachea of mice instead.In the ER+LPS group and ER group,100 mg/kg of edotinib was instilled into stomach of mice,and one hour later.2 mg/kg LPS was instilled into trachea of mice in ER+PLS group to induce lung injury.Twenty-four hours later,bronchoalveolar lavage fluid (BALF) and lung tissue of mice in four groups were collected.HE staining were used for evaluating pathological changes of lung injury.Lung wet/dry weight ratio,protein concentrations and total cell numbers in the BALF were measured to determine the degree of pulmonary edema.Immunohistochemical staining and Western Blot were used for testing the protein expression of SP-A,Data of multiple groups were analyzed by one way variance (ANOVA) and inter-group comparisons were made by the least significant difference (LSD) tests.Results There was no significant difference in lung injury score (LIS) between control group (0.056±0.008) and ER (0.064±0.037) group,The LIS in LPS group (0.846-±0.047) was higher than that in control group,however the LIS in ER+LPS group (0.279±0.020) was significant lower than that in LPS group (P ＜ 0.05).Lung wet/dry weight,SP-A concentration and total cell numbers in the bronchoalveolar lavage fluid revealed that the degree of pulmonary edema in LPS group was higher than that in control group,and this pulmonary edema was reversed by erlotinib treatment.Immunohistochemical staining and Western blot showed that the expression of SP-A in LPS group was decreased compared with control group,but it was recovered after erlotinib treatment (P ＜ 0.05).Conclusions Erlotinib could protect the LPS-induced ALI,and it may be related to the regulation of SP-A.

Decreased expression of surfactant protein C in lung tissue of chronic obstructive pulmonary disease rats / 基础医学与临床

Objective To study the role of surfactant protein C ( SP-C) in rat lung of chronic obstructive pulmonary disease (COPD).Methods Forty healthy conventional Sprague-Dawley (SD) rats were randomly divided into four groups , normal control group ( control group ) , smoke exposure group ( smoking group ) , lipopolysaccharide group (LPS group), smoke exposure +Lipopolysaccharide group (COPD group).The arterial partial pressure oxygen (PaO2) and arterial partial pressure of carbon dioxide pathological (PaCO2) were detected.The ultrastructure of lung tissue was observed by transmission electron microscope .Enzyme-linked immuno sorbent assay (ELISA) were performed to determine protein expression of SP-C in lung and bronchoalveolar lavage fluid ( BALF).RT-qPCR were performed to determine mRNA expression of SP-C in lung.Results Compared with control group , smoking group and LPS group, the PaO2 of COPD group was obviously lower , the PaCO2 of COPD group was obviously higher;the ultrastructure and histological analysis of lung tissues showed chronic inflammatory injury ; Compared with control group , the expression of SP-C protein in was reduced , as well as SP-C mRNA expression .Conclusions The expression of SP-C in lung of rats COPD model is down-regulated.SP-C may be involved in COPD .

Serum levels of SP-A and SP-D in stage Ⅰ coal workers' pneumoconiosis and their significance / 中国职业医学

OBJECTIVE: To explore the changes of serum levels and significance of surfactant protein( SP) A and SP-D in patients with stage Ⅰ coal workers' pneumoconiosis( CWP). METHODS: A random sampling method was used to select 88 cases of stage Ⅰ CWP patients as the CWP group,50 cases of healthy underground miners with similar dust exposure history as the dust exposure group and 38 cases of ground workers without dust exposure history as the control group. The serum levels of SP-A and SP-D in 3 groups were detected by enzyme-linked immunosorbent assays. RESULTS: The levels of serum SP-A and SP-D in the CWP group and the dust exposure group were higher than that of the control group( P <0. 05). The serum level of SP-D in the CWP group was higher than that of the dust exposure group( P < 0. 01). The serum level of SP-D in the smoking CWP subgroup was lower than that of the non-smoking CWP subgroup( P < 0. 05).CONCLUSION: The abnormal serum levels of SP-A and SP-D were related to the development of stage Ⅰ CWP. Smoking might affect the serum level of SP-D in stage Ⅰ CWP patients.

Protective effects of bone marrow mesenchymal stem cell-derived exosomes on smoke inhalation injury in rats / 医学研究生学报

Objective Acute lung injury induced by variety causes can be reduced by mesenchymal stem cells.Some studies have shown that mesenchymal stem cell-derived exosomes have similar features with mesenchymal stem cell,but its role in acute lung injury is less studied.The study was to investigate the protective role and underlying mechanisms of bone marrow mesenchymal stem cell-derived exosomes (BMSC-DEs) on smoke inhalation injury (SⅡ) in rats.Methods Thirty Wistar rats were randomly divided into 3 equal groups:normal control group,smoke inhalation injury (SⅡ) model group and bone marrow mesenchymal stem cell-derived exosomes (BMSC-DEs) treated group.12 h after establishing the SⅡ model,BMSC-DEs treated group was injected with 0.5 mL BMSC-DEs (derived from 4× 106 BMSCs),and normal control group and SⅡ model group were injected with equivalent volume of normal saline.7 days later,samples were collected.The histopathologic changes of lung were observed after HE staining;BCA was used to test the amounts of total protein in bronchoalveolar lavage fluid (BALF);Enzyme linked immunosorbent assay was used to test the levels of tumor necrosis factor-α (TNF-α) and keratinocyte growth factor (KGF) in the lung tissue;Immunohistochemical was used to test the levels of pulmonary surfactant protein C(SP-C).Results The BALF levels of total protein of SⅡ group was significantly higher than those of normal control group (P＜0.01) and BMSC-DEs groups(P＜0.05);Compared with normal group [(0.164±0.021) ng/L],the levels of tumor necrosis factor-α of SII and BMSC-DEs groups [(0.355±0.106)、(0.234±0.024) ng/L] (P＜ 0.05) were significantly higher,and SⅡ group was higher than that of BMSC-DEs group(P＜0.01);Compared with normal group,the KGF protein expression level in lung tissue of SⅡ group was significantly lower (P＜0.05),but BMSC-DEs group was higher (P＜0.05).BMSC-DEs group was higher than SⅡ group (P＜0.01);Immunohistochemistry showed that the SP-C expression level in lung tissue of SⅡ group was significantly lower than those of other groups (P＜0.05).There was no statistically difference between BMSC-DEs group and control group (P＞0.05).Conclusion BMSC-DEs has a protective effect of smoke inhalation injury rats,the underlying mechanism may be related to BMSC-DEs to reduce inflammation and promote restoration of the alveolar epithelial type Ⅱ.

Determination of Clara cell secretory protein 16 and pulmonary surfactant protein D in children with severe pneumonia and its clinical significance / 临床儿科杂志

Objective To explore the changes of serum Clara cell secretory protein 16 (CC16), pulmonary surfactant protein D (SP-D) in children with pneumonia and its clinical significance. Methods A total of 81 pediatric patients with community-acquired pneumonia were selected, including severe pneumonia with mechanical ventilation group (n=21), severe pneumonia with non-mechanical ventilation group (n=30), mild pneumonia group (n=30), and the control group (n=20) was selected in the physical examination of healthy children over the same period. We detected the concentration of serum CC16, TNF-α, IL-6 and SP-D for the 4 groups by ELISA, and evaluated the clinical values of serum CC16, TNF-α, IL-6 and SP-D for severe pneumonia by using ROC curve.We recorded pulmonary dynamic compliance(Cdyn),airway resistance(Raw),peak inspiratory pressure (PIP), work of breathing (WOB) and other respiratory mechanical parameters, and analyzed the correlations between CC16 and TNF-α, IL-6, SP-D and respiratory mechanical parameters. Results The concentrations of serum CC16 in pneumonia group were all significantly lower than that in the control group, and those in severe pneumonia groups were lower than that in mild pneumonia group, and mechanical ventilation group was lower than that in non-mechanical ventilation; the concentration of serum TNF-α, IL-6 and SP-D in pneumonia groups were all obviously higher than that in the control group, and severe pneumonia group were higher than that in mild pneumonia group, and those in mechanical ventilation group were also higher than that in non-mechanical ventilation group (P<0.05). Compared to that before removing the ventilator, concentration of serum CC16 in severe pneumonia with mechanical ventilation group decreased significantly at 1 hour and lowered down at 72 hours; but the concentration of serum TNF-α, IL-6 and SP-D in severe pneumonia with mechanical ventilation increased significantly at 1 hour and went higher at 72 hours, the differences were all statistically significant (all of P<0.05); compared to that before weaning from the ventilator, the value of Cdyn decreased obviously in severe pneumonia with mechanical ventilation at 72 hours and lowered down at 1 hour; but the values of Raw, PIP, WOB in severe pneumonia with mechanical ventilation increased obviously at 72 hours and more higher at 1 hour, the differences were all statistically significant (all of P<0.05). The concentration of serum CC16 showed all negative correlations with TNF-α, IL-6 and SP-D, but it showed positive correlation with Cdyn(all of P<0.01).In the ROC curve,the area under the ROC curve of CC16,TNF-α,IL-6 and SP-D in serum was 0.905, 0.704, 0.832, 0.825, respectively (for all of which P<0.01). Conclusion The concentrations of serum CC16 and SP-D were associated with the severity of community acquired-pneumonia in children. The level of serum CC16 was positive associated with Cdyn in children with mechanical ventilation. CC16 has better prediction and evaluation effect on the change of severe pneumonia.

Clinical value of surfactant protein-A in exudate pleural effusion / 中南大学学报(医学版)

Objective:To evaluate the clinical value of surfactant protein-A (SP-A) in exudate pleural effusion (EPE).Methods:This clinical study was prospective,observational and cross-sectional.Two hundred and fifteen patients with pleural effusion were divided into the transudate pleural effusions (TPE) group and the EPE group.TPE patients served as the control group.The concentrations of pleural effusions SP-A (SP-Apl) and serum SP-A (SP-Ase) were measured by ELISA,and receiver operator characteristic (ROC) curve and multivarate Cox analysis of SP-A was analysed for its clinical value.Results:SP-Apl concentrations in the EPE group were significantly higher than that in the TPE group [(189.8±43.4) ng/mLvs (22.3±5.1) ng/mL,P＜0.01];SP-Ase concentrations in the EPE group were higher than that in the TPE group [(78.9±11.3) ng/mL vs (25.8±12.4) ng/mL,P＜0.05];SP-Apl concentrations were significantly higher than the concentrations of SP-Ase in the EPE group (P＜0.01).In EPE group,SP-Apl and SP-Ase concentration in the patients with primary lung adenocarcinomas were the highest.The cut off value of SP-Apl concentrations was more than 484.5 ng/mL,yielding a 85.4％ sensitivity and 95.2％ specificity for diagnosing primary lung adenocarcinomas,with an area under the curve (AUC) of 0.943 (95％ CI 0.852 to 0.934,P＜0.01);when SP-Ase concentration was more than 84.2 ng/mL,it yielded a 76.4％ sensitivity and 94.3％ specificity for diagnosing primary lung adenocarcinomas,with an AUC of 0.910 (95％ CI 0.921 to 0.953,P＜0.01).Conclusion:While SP-Apl concentration is more than 484.5 ng/mL and/or SP-Ase concentration is more than 84.2 ng/mL,it may be helpful for the diagnosis of primary lung adenocarcinomas with the usage ofpleural effusion.