Establishment and validation of nomogram for predicting immuno checkpoint inhibitor related pneumonia.

OBJECTIVE: Cancer is one of the main causes of death worldwide. Although immunotherapy brings hope for cancer treatment, it is also accompanied by immune checkpoint inhibitor-related adverse events (irAEs). Immune checkpoint inhibitor pneumonia (CIP) is a potentially fatal adverse event, but there is still a lack of effective markers and prediction models to identify patients at increased risk of CIP. METHODS: A total of 369 cancer patients treated between 2017 and 2022 with immune checkpoint inhibitors at Shengjing Hospital of China Medical University and Liaoning People's Hospital were recruited for this study. Independent variables were selected by differences and binary logistic regression analysis, and a risk assessment nomogram was constructed for CIP risk. The accuracy and discriminative abilities of the nomogram were evaluated by calibration plots, receiver operating characteristic curves (ROCs) and decision curve analyses (DCAs). RESULTS: Binary logistic regression analysis showed that smoking history, acute phase proteins [interleukin (IL-6) and C-reactive protein (CRP)], CD8 + T lymphocyte count and serum alveolar protein [surface protein-A (SP-A) and Krebs Von den Lungen-6 (KL-6)] were significantly associated with CIP risk. A nomogram consisting of these variables was established and validated by different analyses. CONCLUSIONS: We developed an effective risk nomogram for CIP prediction in immune-checkpoint inhibitor administrated cancer patients, which will further assist early detection of immunotherapy-related adverse events.

Surfactant Protein A and Microbiome Composition in Patients With Atraumatic Intraoral Lesions.

Oral ulcers are lesions that occur due to disruption of epithelial integrity of the mucosa of the oral cavity. Intraoral ulcers are often associated with pain, redness, symptoms of discomfort, and blood hemorrhage. The etiology for many oral ulcers is local trauma, systemic health conditions, or medication; for other ulcers the cause is less clear. This pilot study aims to evaluate the salivary components and microbiome in patients with atraumatic pre-ulcerous and ulcerous oral lesions compared to control individuals, while considering three common risk factors for atraumatic ulcers, smoking, stress, and gender. This study uses matched age, sex, and ethnicity samples from healthy otherwise and oral lesion patients to investigate the changes in salivary surfactant protein A (SP-A) and examines the prevalence and diversity of the salivary oral microflora. The goal is to determine if there are factors in saliva that have the potential to be used as biomarkers for risk of developing atraumatic oral ulcers. Our data show that the average level of SP-A is significantly reduced in female smokers compared to non-smoker healthy females. The average level of SP-A in female oral lesion patients is reduced compared to controls. The microbiome composition is significantly affected by smoking and the level of SP-A. Comparing the control participants and oral lesion patients, there are 16 species of bacteria that are significantly different, and all of these bacteria are significantly affected by smoking and SP-A. LEfSe analysis identified five bacteria that may represent potential biomarkers. This preliminary study demonstrates the potential of the oral microbiome to act as a biomarker for oral ulcer risk and infers potential mechanistic links between risk factors and alterations in innate immune mechanisms such as SP-A levels.

[Effects of aerosol inhalation of recombinant human keratinocyte growth factor 2 on the lung tissue of rabbits with severe smoke inhalation injury].

Objective: To investigate the effect of recombinant human keratinocyte growth factor 2 (rhKGF-2) on lung tissue of rabbits with severe smoke inhalation injury. Methods: A total of 120 New Zealand rabbits were divided into 5 groups by random number table after being inflicted with severe smoke inhalation injury, with 24 rats in each group. Rabbits in the simple injury group inhaled air, while rabbits in the injury+phosphate buffer solution (PBS) group inhaled 5 mL PBS once daily for 7 d. Rabbits in injury+1 mg/kg rhKGF-2 group, injury+2 mg/kg rhKGF-2 group, and injury+5 mg/kg rhKGF-2 group received aerosol inhalation of 1 mg/kg, 2 mg/kg, and 5 mg/kg rhKGF-2 (all dissolved in 5 mL PBS) once daily for 7 d, respectively. On treatment day 1, 3, 5, and 7, blood samples were taken from the ear central artery of 6 rabbits in each group. After the blood was taken, the rabbits were sacrificed, and the tracheal carina tissue and lung were collected. Blood pH value, arterial oxygen partial pressure (PaO(2)), arterial blood carbon dioxide pressure (PaCO(2)), and bicarbonate ion were detected by handheld blood analyzer. The expressions of pulmonary surfactant-associated protein A (SP-A) and vascular endothelial growth factor (VEGF) in lung tissue were detected by Western blotting. Pathomorphology of lung tissue and trachea was observed by hematoxylin-eosin staining. Data were processed with analysis of variance of two-way factorial design and Tukey test. Results: (1) Compared with those in simple injury group, the blood pH values of rabbits in the latter groups on treatment day 1-7 had no obvious change (P>0.05). The PaO(2) of rabbits in injury+2 mg/kg rhKGF-2 group on treatment day 5 and 7 were (75.0±2.4) and (71.0±4.5) mmHg (1 mmHg=0.133 kPa), respectively, which were significantly higher than (62.0±6.8) and (63.0±3.0) mmHg in simple injury group (q=4.265, 8.202, P<0.05 or P<0.01). The PaO(2) of rabbits in injury+5 mg/kg rhKGF-2 group on treatment day 7 was (82.0±4.9) mmHg, which was significantly higher than that in simple injury group (q=6.234, P<0.01). Compared with that in simple injury group, the PaCO(2) of rabbits in injury+2 mg/kg rhKGF-2 group on treatment day 3 was significantly decreased (q=4.876, P<0.01) and significantly increased on treatment day 5 (q=5.562, P<0.01); the PaCO(2) of rabbits in injury+5 mg/kg rhKGF-2 group was significantly increased on treatment day 5 and 7 (q=5.013, 4.601, P<0.05 or P<0.01). Compared with that in simple injury group, the serum bicarbonate ion of rabbits in injury+1 mg/kg rhKGF-2 group on treatment day 7 was significantly increased (q=5.142, P<0.01); the serum bicarbonate ion of rabbits in injury+2 mg/kg rhKGF-2 group on treatment day 5 and 7 were significantly increased (q=4.830, 6.934, P<0.01); the serum bicarbonate ion of rabbits in injury+5 mg/kg rhKGF-2 group on treatment day 5 were significantly increased (q=3.973, P<0.05). (2) The expressions of SP-A in lung tissue of rabbits in simple injury group and injury+PBS group in each treatment time point were close (P>0.05). The expressions of SP-A in lung tissue of rabbits in injury+2 mg/kg rhKGF-2 group and injury+5 mg/kg rhKGF-2 group on treatment day 3 were 0.091±0.007 and 0.101±0.009, respectively, significantly higher than 0.069±0.009 in simple injury group (q=10.800, 13.580, P<0.01). The expressions of SP-A in lung tissue of rabbits in injury+1 mg/kg rhKGF-2 group, injury+2 mg/kg rhKGF-2 group, and injury+5 mg/kg rhKGF-2 group on treatment day 5 and 7 were 0.127±0.008, 0.132±0.006, 0.194±0.006, 0.152±0.017, 0.166±0.004, 0.240±0.008, significantly higher than 0.092±0.003 and 0.108±0.005 in simple injury group (q=6.789, 12.340, 17.900, 9.875, 31.480, 40.740, P<0.01). (3) On treatment day 1 and 5, there was no significant difference in the expression of VEGF in lung tissue of rabbits among the 5 groups (P>0.05). Compared with those in simple injury group, the expressions of VEGF in lung tissue of rabbits in injury+2 mg/kg rhKGF-2 group on treatment day 3 and 7 were significantly increased (q=4.243, 8.000, P<0.05 or P<0.01), and the expression of VEGF in lung tissue of rabbits in injury+5 mg/kg rhKGF-2 group on treatment day 7 was significantly increased (q=20.720, P<0.01). (4) On treatment day 1, the injury of rabbits in each group was similar, with a large number of neutrophils infiltrated and abscess formed in the alveolar and interstitial tissue, thickened alveolar septum, some collapsed alveolar and atelectasis; large area of tracheal mucosa was degenerated and necrotic, with a large amount of inflammatory exudates blocking in the cavity. On treatment day 3, the inflammation of lung tissue and trachea in each group were improved, but the inflammation in simple injury group and injury+PBS group was also serious. On treatment day 5, the inflammation in lung tissue and trachea of rabbits in injury+2 mg/kg rhKGF-2 group and injury+5 mg/kg rhKGF-2 group were improved much obviously than those in the other groups. On treatment day 7, the inflammation in lung tissue of rabbits in injury+5 mg/kg rhKGF-2 group alleviated obviously than those in the other groups, most alveoli had no obvious exudative fluid, the alveolar cavity was intact and clear, the local alveolar dilated like a cyst, and the alveolar septum thinning; the improvement of inflammation of trachea was more obvious than the other groups, the tracheal mucosa tended to be more complete, and few neutrophils were infiltrated in the endotracheal cavity. Conclusions: Atomization inhalation of rhKGF-2 can improve the PaO(2) level of rabbits with severe smoke inhalation injury, reduce airway inflammation, increase the expression of SP-A and VEGF in lung tissue, thus promoting the repair of lung tissue.

Immunohistochemical analysis and comparison of napsin A, TTF1, SPA and CK7 expression in primary lung adenocarcinoma.

We investigated the expression of napsin A, TTF1, SPA and CK7 in primary lung adenocarcinoma (ADC) and compared antibody specificity and sensitivity. We used immunohistochemistry (IHC) using antibodies directed against napsin A, TTF1, SPA, and CK7 on cancer tissue from 454 patients diagnosed with lung cancer. In primary lung ADC, napsin A exhibited a sensitivity of 87.25% and specificity of 95.02%, TTF1 exhibited a sensitivity of 80.72% and specificity of 90.48%, SPA exhibited a sensitivity of 60.46% and specificity of 94.87% and CK7 exhibited a sensitivity of 100% and specificity of 80.31%. The order of sensitivity of the four indicators was CK7 > napsin A > TTF1 > SPA, and the order of specificity was napsin A > SPA > TTF1 > CK7. We can select effective indicators for diagnostic and differential diagnostic purposes based on differences in sensitivity and specificity.

Effects of aerosol inhalation of recombinant human keratinocyte growth factor 2 on the lung tissue of rabbits with severe smoke inhalation injury / 中华烧伤杂志

Objective@#To investigate the effect of recombinant human keratinocyte growth factor 2 (rhKGF-2) on lung tissue of rabbits with severe smoke inhalation injury.@*Methods@#A total of 120 New Zealand rabbits were divided into 5 groups by random number table after being inflicted with severe smoke inhalation injury, with 24 rats in each group. Rabbits in the simple injury group inhaled air, while rabbits in the injury+phosphate buffer solution (PBS) group inhaled 5 mL PBS once daily for 7 d. Rabbits in injury+1 mg/kg rhKGF-2 group, injury+2 mg/kg rhKGF-2 group, and injury+5 mg/kg rhKGF-2 group received aerosol inhalation of 1 mg/kg, 2 mg/kg, and 5 mg/kg rhKGF-2 (all dissolved in 5 mL PBS) once daily for 7 d, respectively. On treatment day 1, 3, 5, and 7, blood samples were taken from the ear central artery of 6 rabbits in each group. After the blood was taken, the rabbits were sacrificed, and the tracheal carina tissue and lung were collected. Blood pH value, arterial oxygen partial pressure (PaO2), arterial blood carbon dioxide pressure (PaCO2), and bicarbonate ion were detected by handheld blood analyzer. The expressions of pulmonary surfactant-associated protein A (SP-A) and vascular endothelial growth factor (VEGF) in lung tissue were detected by Western blotting. Pathomorphology of lung tissue and trachea was observed by hematoxylin-eosin staining. Data were processed with analysis of variance of two-way factorial design and Tukey test.@*Results@#(1) Compared with those in simple injury group, the blood pH values of rabbits in the latter groups on treatment day 1-7 had no obvious change (P>0.05). The PaO2 of rabbits in injury+2 mg/kg rhKGF-2 group on treatment day 5 and 7 were (75.0±2.4) and (71.0±4.5) mmHg (1 mmHg=0.133 kPa), respectively, which were significantly higher than (62.0±6.8) and (63.0±3.0) mmHg in simple injury group (q=4.265, 8.202, P<0.05 or P<0.01). The PaO2 of rabbits in injury+5 mg/kg rhKGF-2 group on treatment day 7 was (82.0±4.9) mmHg, which was significantly higher than that in simple injury group (q=6.234, P<0.01). Compared with that in simple injury group, the PaCO2 of rabbits in injury+2 mg/kg rhKGF-2 group on treatment day 3 was significantly decreased (q=4.876, P<0.01) and significantly increased on treatment day 5 (q=5.562, P<0.01); the PaCO2 of rabbits in injury+5 mg/kg rhKGF-2 group was significantly increased on treatment day 5 and 7 (q=5.013, 4.601, P<0.05 or P<0.01). Compared with that in simple injury group, the serum bicarbonate ion of rabbits in injury+1 mg/kg rhKGF-2 group on treatment day 7 was significantly increased (q=5.142, P<0.01); the serum bicarbonate ion of rabbits in injury+2 mg/kg rhKGF-2 group on treatment day 5 and 7 were significantly increased (q=4.830, 6.934, P<0.01); the serum bicarbonate ion of rabbits in injury+5 mg/kg rhKGF-2 group on treatment day 5 were significantly increased (q=3.973, P<0.05). (2) The expressions of SP-A in lung tissue of rabbits in simple injury group and injury+PBS group in each treatment time point were close (P>0.05). The expressions of SP-A in lung tissue of rabbits in injury+2 mg/kg rhKGF-2 group and injury+5 mg/kg rhKGF-2 group on treatment day 3 were 0.091±0.007 and 0.101±0.009, respectively, significantly higher than 0.069±0.009 in simple injury group (q=10.800, 13.580, P<0.01). The expressions of SP-A in lung tissue of rabbits in injury+1 mg/kg rhKGF-2 group, injury+2 mg/kg rhKGF-2 group, and injury+5 mg/kg rhKGF-2 group on treatment day 5 and 7 were 0.127±0.008, 0.132±0.006, 0.194±0.006, 0.152±0.017, 0.166±0.004, 0.240±0.008, significantly higher than 0.092±0.003 and 0.108±0.005 in simple injury group (q=6.789, 12.340, 17.900, 9.875, 31.480, 40.740, P<0.01). (3) On treatment day 1 and 5, there was no significant difference in the expression of VEGF in lung tissue of rabbits among the 5 groups (P>0.05). Compared with those in simple injury group, the expressions of VEGF in lung tissue of rabbits in injury+2 mg/kg rhKGF-2 group on treatment day 3 and 7 were significantly increased (q=4.243, 8.000, P<0.05 or P<0.01), and the expression of VEGF in lung tissue of rabbits in injury+5 mg/kg rhKGF-2 group on treatment day 7 was significantly increased (q=20.720, P<0.01). (4) On treatment day 1, the injury of rabbits in each group was similar, with a large number of neutrophils infiltrated and abscess formed in the alveolar and interstitial tissue, thickened alveolar septum, some collapsed alveolar and atelectasis; large area of tracheal mucosa was degenerated and necrotic, with a large amount of inflammatory exudates blocking in the cavity. On treatment day 3, the inflammation of lung tissue and trachea in each group were improved, but the inflammation in simple injury group and injury+PBS group was also serious. On treatment day 5, the inflammation in lung tissue and trachea of rabbits in injury+2 mg/kg rhKGF-2 group and injury+5 mg/kg rhKGF-2 group were improved much obviously than those in the other groups. On treatment day 7, the inflammation in lung tissue of rabbits in injury+5 mg/kg rhKGF-2 group alleviated obviously than those in the other groups, most alveoli had no obvious exudative fluid, the alveolar cavity was intact and clear, the local alveolar dilated like a cyst, and the alveolar septum thinning; the improvement of inflammation of trachea was more obvious than the other groups, the tracheal mucosa tended to be more complete, and few neutrophils were infiltrated in the endotracheal cavity.@*Conclusions@#Atomization inhalation of rhKGF-2 can improve the PaO2 level of rabbits with severe smoke inhalation injury, reduce airway inflammation, increase the expression of SP-A and VEGF in lung tissue, thus promoting the repair of lung tissue.

Effect of parecoxib sodium on serum surfactant protein A and inflammatory response in elderly patients undergoing video-assisted thoracoscopic pneumonectomy / 临床麻醉学杂志

Objective To investigate the effects of perioperative parecoxib sodium on serum surfactant protein A and inflammatory response in elderly patients undergoing video-assisted thoracoscopic pneumonectomy,Methods Sixty-two ASA Ⅰ or Ⅱ elderly patients,aged 65-78 years,weighing 51-79 kg,scheduled for elective video-assisted thoracoscopic pneumonectomy under general anesthesia,were randomly divided into 3 groups:0.3 mg/kg parecoxib sodium group (group P1,n=21),0.6 mg/kg parecoxib sodium group (group P2,n =21) and control group (group C,n =20).The patients were given intravenous parecoxib sodium of 0.3 mg/kg immediately before induction of anesthesia and at 12 h after operation in group P1,and also parecoxib sodium of 0.6mg/kg immediately before induction of anesthesia and at 12 h after operation in group P2,while the equal volume of normal saline was given in group C.Blood samples were taken from the central vein before the induction of anesthesia(T0),after operation(T1),12 h after operation(T2) and 24 h after operation(T3).The concentration of serum surfactant protein A (SP-A),TNF-α,IL-6 and IL-8 were determined by ELASA.The incidence of pulmonary complications at 72 h after operation were also recorded.Results Compared with T0,the concentration of serum SP-A,TNF-α,IL-6 and IL-8 increased significantly in all groups at T1-T3 (P＜0.05).Compared with C group,the concentration of serum SP-A,TNF-α,IL-6 and IL-8 in groups P1 and P2 decreased significantly at T1-T3 (P＜0.05),there were no significant differences between groups P1 and P2.The incidence of postoperative pulmonary complications had no statistically significant differences between the three groups.Conclusion Parecoxib sodium can significantly reduce the concentration of serum SP-A and alleviate the inflammatory response in elderly patients undergoing video-assisted thoracoscopic pneumonectomy.

The effect of preoperative pulmonary protection on surfactant protein A content in lung tissue / 天津医药

Objective To explore the effect of preoperative pulmonary protection therapy on surfactant protein A(SP–A) content in lung tissue and postoperative complications. Methods Sixty patients with non-small cell lung cancer (NSCLC) complicated with chronic obstructive pulmonary disease(COPD) who underwent surgical treatment in Tianjin Chest Hospital from January 2015 to June 2016 were enrolled in this study. Thirty patients were included in the control group and 30 patients in the pulmonary protection group. The control group was given routine preoperative preparation, while the pulmonary protection group was given 1 week pulmonary protection therapy on the basis of routine preoperative preparation. The exhaled breath condensate (EBC) was collected and pulmonary function was re-checked after admission and before surgery. The content of SP-A in EBC was detected by ELISA. The lung tissue samples were collected during surgery, and the SP-A level was measured by Western blotting. Results The SP-A level of the pulmonary protection group was significantly higher than that of the control group (1.05±0.21 vs. 0.93±0.16, P0.05). The average postoperative hospital stay was statistically significant shorter in the pulmonary protection group than that in the control group[(9.2 ± 3.1) d vs. (11.6 ± 4.8) d, P<0.05]. Conclusion Preoperative pulmonary protection therapy can not only improve pulmonary function and shorten postoperative hospital stay, but also improve SP-A content in lung tissue.

Bioinformatics analysis of surfactant-associated protein a in cotton rat and its relationship with lung injury / 第二军医大学学报

Objective To analyze the pulmonary surfactant-associated protein A (SP-A) gene sequence and its bioinforma tic characteristics and to observe SP-A mRNA and protein levels in lung injury model of cotton rats, so as to explore the correlation between lung injury and SP-A expression. Methods A total of 32 cotton rats were randomly divided into control (normal saline, NS) group and three lipopolysaccharide (LPS)-induced lung injury groups (the cotton rats were injected intraperitoneally with 2 mg/kg LPS for 24, 48 and 96 hours, respectively). The total RNA was extracted from lung tissue and SP-A gene was amplified by RT-PCR. Then bioinformatic analysis was done for SP-A characteristics. Histopathological changes of lung tissue were observed at different time points by hematoxylin-eosin staining; the mRNA level of SP-A was detected by real time-PCR and the protein level of SP-A was detected by Western blotting analysis. Results The coding region of cotton rat SP-A gene had 744 bp and encoded 248 amino acids, containing six cysteine conserved sites, four crhelices and two predicted N-glycosylation sites. Meanwhile, cotton rat SP-A shared high level of homology in the nucleotide sequences (75. 4%-90. 1%) and in deduced amino acid sequences (70. 6%-87. 1%) with other species. Moreover, histopathological changes of lung tissues in three LPS groups were more notable and severe than those in the control group, and the changes were related to LPS treatment time. Compared with the control group, the mRNA and protein levels of SP-A in lung tissues were significantly increased in three LPS groups, with rapid increase starting from 24 h after treatment (P<0. 001, P<0. 01), with continuous increase at 48 h (P<0. 001 and P<0. 01), and slight decrease and still keeping at a high level at 96 h (P<0. 05, P<0. 01). Conclusion SP-A gene of cotton rat is highly conservative; the mRNA and protein levels of SP-A are closely associated with the severity of lung injury.

Effect research of two kinds of airway humidification solution for patients with tracheotomy of airway humidification / 中国实用护理杂志

Objective To compare the influence of tracheotomy after two wet fluid on airway and provide the basis for clinical treatment and care. Methods A total of 30 patients with severe brain injury stay neurosurgery tracheotomy were divided into 0.45% sodium chloride group and ambroxol hydrochloride group with 15 cases each by random digits table method, two airway humidification liquid (0.45%sodium chloride,0.9% sodium chloride + ambroxol hydrochloride) were each instilled in the trachea inner sleeve. Blood gas analysis was performed and the levels of serum lung surface active substances related protein-A (SP-A protein), interleukin-6, interleukin-8, tumor necrosis factor-alpha(TNF-α) were measured by enzyme linked immunosorbent assay (ELISA) before 1 d and after 3,7,14 d of tracheotomy. Results There were significant differences in arterial blood oxygen partial pressure, arterial carbon dioxide partial pressure, oxygenation index after 14 d of tracheotomy between ambroxol hydrochloride group and 0.45% sodium chloride group:(110.72±26.75) mmHg(1 mmHg=0.133 kPa) vs.(89.39±21.98) mmHg, (30.44±6.75) mmHg vs. (35.12±7.28) mmHg, 333.23±80.56 vs. 270.93±77.21, t=29.49,-8.63,7.44, P<0.01.There were significant differences in the levels of serum SP-A protein, interleukin -6, interleukin -8, TNF-α after 14 d of tracheotomy between ambroxol hydrochloride group and 0.45% sodium chloride group:(191.34 ±1.21) ng/L vs. (61.92 ±12.0) ng/L, (2.62 ±0.23) ng/L vs. (5.42 ±0.16) ng/L, (124.56 ±2.10) ng/L vs. (185.91 ±1.48) ng/L, (31.32±1.38) ng/L vs.(69.13±1.16) ng/L, t=75.72,-13.51,-23.89,-20.97, P<0.01. Conclusions The airway humidification effect of ambroxol hydrochloride group is better than 0.45%sodium chloride group, it can improve the wetting effect, and better protect the lung tissue, reduce the incidence of lung infection, make it an ideal airway humidification liquid.

Surfactant protein A is decreased in the lung of rats with hepatopulmonary syndrome

PURPOSE: To evaluate surfactant protein A levels in an hepatopulmonary syndrome rat model. To date, there have been no studies aimed at evaluating surfactant levels in the setting of cirrhosis or hepatopulmonary syndrome. METHODS: A total of 35 rats were divided into control, sham, and experimental HPS groups. We evaluated surfactant protein A levels in rats and the experimental model designed to induce hepatopulmonary syndrome was common bile duct ligation. Statistical analysis was performed using GraphPad Prism Software(r). Differences were considered statistically significant when p<0.05. RESULTS: Lung homogenate of surfactant protein A levels were lower in the experimental hepatopulmonary syndrome and sham groups in comparison to the control group (p<0.05). Serum SP-A levels were the same in experimental hepatopulmonary syndrome and control groups but decreased in the sham group compared with the experimental groups (p<0.05). Myeloperoxidase activity was higher in the experimental hepatopulmonary syndrome group than the other two groups (p<0.05). CONCLUSION: Surfactant protein A is present in experimental hepatopulmonary syndrome and leads to an imbalance between serum and pulmonary levels due to systemic inflammatory response. .

The changes of pulmonary surfactant associated protein of sputum and oxygenation index in dysfunctional ventilatory weaning response patients / 重庆医学

Objective To explore the expression of SP-A in surface active substance of sputum pulmonary of dysfunctional venti-latory weaning response patients and to study changes of expression of SP-A and oxygenation index ,arterial partial pressure of oxy-gen .Methods The mechanical ventilatory patients were divide into dysfunctional ventilatory weaning response group (group A) and easily weaning group(group B) ,then collected sputum from ventilators at different times :on the first day ,two and seven days after using ventilators .Used ELISA to test level of SP-A and oxygenation index ,arterial partial pressure of oxygen in sputum of group A and group B .Results For group A ,SP-A content oxygenation index and arterial partial pressure of oxygen were significantly less than those for group B(P0 .05) .Con-clusion Dysfunctional ventilatory weaning response and lung injury related to ventilator can be diagnosed early through the test of SP-A content in sputum ,which provides a brand-new way and method of treatment in dysfunctional ventilatory weaning response and lung injury related to ventilator .

Role of cAMP-PKA signal transduction pathway in lidocaine-induced up-regulation of expression of surfactant protein-A in rat alveolar epithelial type Ⅱ cells / 中华麻醉学杂志

Objective To evaluate the role of cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) signal transduction pathway in lidocaine-induced up-regulation of the expression of surfactant protein-A (SP-A) in rat alveolar epithelial type Ⅱ cells (AEC Ⅱ).Methods Healthy male Sprague-Dawley rats were sacrificed and AEC Ⅱ were isolated,purified and incubated in 24-well culture plates (100μd/hole) with density of 1 × 106/ml.After being incubated for 2 h,the culture medium was replaced with serum-free medium DMEM.The cells were randomly divided into 4 groups (n =48 each):control group (group C),forskolin (adenylate cyclase agonist) group (group F),lidocaine 200 μg/ml group (group L),and PKA inhibitor H89 + L group (group P+ L).Forskolin 10 μmol/ml was added to DMEM in group F.Lidocaine 200 μg/ml was added to DMEM in group L.H89 10μnol/ ml was added to DMEM and AEC Ⅱ were incubated for 10 min,and then lidocaine 200 μg/ml was added in group P + L.At 6,12 and 24 h of incubation (T1-3),cAMP content and PKA activity (using ELISA),and expression of SP-A mRNA (by real-time fluorescent quantitative PCR) and SP-A (by Western blot) were measured.Results Compared with group C,the expression of SP-A mRNA and SP-A was significantly upregulated,and cAMP level and PKA activity were increased at T1-3 in group F and at T2,3 in group L.Compared with group L,the expression of SP-A and SP-A mRNA was down-regulated,PKA activity was decreased,and no significant change was found in cAMP level at T1-3 in group P + L.Conclusion Lidocaine can up-regulate the expression of SP-A in AEC Ⅱ of rats through activating cAMP-PKA signal transduction pathway.

Effects of mechanical ventilation method on inflammatory factors and pulmonary surfactant associated protein A of bronchoalveolar lavage fluid in newborn piglets with acute lung injury / 中华实用儿科临床杂志

Objective To investigate the effects of 3 different ventilation methods,including conventional mechanical ventilation (CMV),high frequency oscillatory ventilation(HFOV) and partial liquid ventilation (PLV),on the changes of inflammatory factors and pulmonary surfactant associated protein A (SP-A) in bronchoalveolar lavage fluid (BALF) in newborn piglets with acute lung injury(ALI).Methods Twenty-four newborn piglets,no more than 3 days old,were enrolled.After ALI made with saline lavage(38 ℃,35 mL/kg),newborn piglets were randomly assigned to 4 groups:control group (n =6,no ventilation),CMV group(n =6),HFOV group(n =6),and PLV group(n =6).Piglets were sacrificed after being ventilated for 24 h.Tumor necrosis factor-α (TNF-α),interleukin-8 (IL-8),interleukin-1 (IL-1) and SP-A in BALF were measured quantitatively by using enzyme-linked immunosorbent assay.Results In 3 groups using different ventilation methods,the population mean of TNF-o,IL-8,IL-1 and SP-A were statistically different (all P =0.000).SP-A in PLV group and HFOV group were higher than that in CMV group (all P ＜ 0.05),while IL-8,IL-1 and TNF-α in PLV group were lower than those in CMV group (all P ＜ 0.05),IL-8 and TNF-α in PLV group were lower than those in HFOV group (all P ＜ 0.05),IL-8 and TNF-α in HFOV group were lower than those in CMV group (all P ＜ 0.05).Conclusions Pulmonary inflammatory reaction was different in 3 ventilation groups.Compared with CMV and HFOV,PLV attenuated inflammatory reaction,so it could increase the expression of SP-A and decrease the degradation of SP-A.

Relationship between total bile acid concentration and fetal pulmonary surfactant in intrahepatic cholestasis of pregnancy / 中华妇产科杂志

Objective To explore the relationship between total bile acid(TBA)concentration and fetal pulmonary surfactant in intrahepatic cholestasis of pregnancy(ICP).Methods Fifry five patients with ICP(ICP group)who received cesarean section from April 2008 to February 2010 in Second Xiangya Hospital,Central South University,were recruited.The general conditions of the neonates within 7 days after birth in ICP group were recorded.Those with fetal distress,neonatal asphyxia,or neonatal respiratory distress syndrome were referred as pathological neonates, others were referred as normal neonates. Over the same period, 23 healthy gravidas were recruited as control group. Enzymatic method was used to detect the TBA concentrations in maternal blood, cord blood and amniotic fluid. ELISA was employed to measure the urfactant protein A (SP-A) concentration in cord blood. High performance liquid chromatography system was used to detect the concentrations of phesphatidylcholine (PC),phosphatidylinositol (PI),lysophosphatidylcholine ( LPC), and sphingomyelin(SM) in amniotic fluid. Results ( 1 ) The concentrations of TBA in maternal blood, cord blood and amniotic fluid were ( 30. 1 ± 7.9 ), (9. 3± 3. 3 ) and (4. 4 ± 1.5 ) mmol/L in ICP group, (4. 8 ± 2. 2), (4. 9 ± 0. 9) and ( 1.4 v 1.1 ) mmol/L in control group, respectively. The differences between the two groups were significant ( P ＜ 0. 05 ). ( 2 ) The SP-A concentration in cord blood in ICP group was ( 29. 5 ± 6. 4 ) μg/L, significantly higher than that in control group, which was ( 22. 6 ± 7. 4 )μg/L ( P＜ 0. 05 ). ( 3 ) There were 20 pathological neonates and 35 normal neonates in ICP group. In pathological neonates, the concentrations of TBA and SP-A in cord blood were (10.9 ± 2.2) mmol/L,(37.0 ± 5.9 ) μg/L, respectively; and were ( 8.0 ± 2. 8 ) mmol/L, ( 26. 7 ± 4. 8 ) μg/L in normal neonates. The differences were significant (P＜ 0. 05 ). (4) There was a positive correlation between TBA concentration in cord blood and in maternal blood ( r1 = 0. 706, P＜0. 05 ). The TBA concentration in cord blood was positively correlated with SP-A concentration as well ( r3 = 0. 494,P ＜ 0. 05 ). (5) The PC and PI concentrations in amniotic fluid were (65.4 ± 7.2) mg/L and ( 3. 8 ± 0. 6 ) mg/L in ICP group, ( 69. 7 ±3.7) mg/L and (4. 3 ± 0. 7 ) mg/L in control group, respectively. The differences were significant (P ＜0. 05 ). The concentration of LPC in amniotic fluid in ICP group was (4. 8 ±0. 9) mg/L, significantly higher than that in control group (P＜0. 05), which was (4. 2 ±0. 6) mg/L. The concentration of SM in amniotic fluid was (3.5±0. 8) mg/L in ICP group, (4. 0 ± 0. 5 ) mg/L in control group, with no significant difference ( P＞0. 05 ). (6) The ratio of PC/LPC in ICP group ( 14. 2± 3. 2 ) was significantly lower than that in control group ( 16. 9 ± 2. 5 ) ( P＜ 0. 05 ). ( 7 ) The TBA concentration in cord blood was negatively correlated with PC and PI concentrations (r1 = -0. 561, r2 = -0. 407, P ＜ 0. 05 ), and had no correlation with LPC concentration (r3 = 0. 260, P＞ 0. 05). Conclusions ( 1 ) The fetal TBA concentrations in both cord blood and amniotic fluid of patients with ICP was higher than those of healthy gravidas, they were also positively correlated with maternal TBA concentration. (2) ICP resulted in the change of fetal pulmonary surfactant and this change was associated with TBA concentrations in both cord blood and amniotic fluid.

The immunohistochemical analysis of AGEs, SP-A in the lung of diabetic rats / 中国医师杂志

Objective To approach the changes of advanced glycosylated end products (AGEs),surfactant proteins A (SP-A) in the lung of experimental diabetic rats and their relationship. Methods 48 male SD rats were divided into diabetes mellitus (DM) group and control group, each group with 24 rats.The DM rat model was made by injecting streptozocin (60mg/kg) into caudal vein. The rats were killed and the lung was individually taken out at the end of 4, 12 and 20 weeks after the models were established. The changes of AGEs, SP-A in rats lung were observed with immunohistochemical assay and the images were analyzed( black is minimum of gray, white is maximum of gray ). Results We observed a great quantity of AGEs positive cells in the alveolar epithelial cells, bronchial mucosal epithelium, angio-endothelial cell and smooth muscle cells of the DM rats. The average gray (AG) was inferior to that of the controls(4weeks 93.92 ± 7.92 vs 104. 75 ± 8. 20; 12 weeks 76. 25 ± 6. 76 vs 93.50 ± 7.56; 20 weeks 47.63 ± 7.96 vs 142. 38 ± 19. 76; P ＜0. 05) and decreased with the DM course. In the 4 weeks DM rats, there were a few SP-A positive cells in the type Ⅱ alveolar epithelial cells, Clara cells and alveolar macrophage cells. In the 12 and 20 weeks DM rats, there were a great many CTGF and TGF-β1 positive cells. The AG was inferior to that of the controls( 12 weeks 75.63 ± 6. 70 vs 110. 50 ± 13.20;20 weeks 47.38 ± 4. 84 vs 97. 25 ± 9. 87; P ＜ 0. 01 ). Conclusion With the progress of diabetes, DM rats' pulmonary alveolar type Ⅱ cells injury appeared, that might be related with the deposition of AGEs.

Expression of surfactant protein A in lung carcinoma and its clinical significance / 国际检验医学杂志

Objective To investigate the expression of surfactant protein A(SP-A)in adenocarcinoma and squamous cell carcinoma of lung and its clinical significance.Methods The expression of SP-A was determined by immunohistochemical assay (EnVision) in 27 cases of adenocarcinoma,15 cases of squamous cell carcinoma of lung.Then the association of SP-A expression with clinicopathological parameters was analyzed.Results The expression rate of SP-A was significantly higher in adenocarcinoma of lung than that in squamous cell carcinoma of lung(51.85% vs 6.67%,P<0.01).The expression rate of SP-A in papillary adenocarcinoma,bronchioloalveolar carcinoma,acinar adenocarcinoma and musinous adenocarcinoma of lung was respectively 85.71%,50%,40%and 25%.There was no correlation between the expression of SP-A and gender,age,tumor size and lymph node metastasia.Conclusion The expression of SP-A may be associated with histological types of the lung carcinoma,which may be used as important marker in differential diagnosis of adenocarcinoma and squamous cell carcinoma of lung.

Effects of curosurf on neonatal respiratory distress syndrome by different administration means / 中国基层医药

Objective To evaluate the curative and prophylactic effects of pulmonary surfactant (PS) on neonatal respiratory distress syndrome (NRDS) by two different administration means. Methods 35 neonates with NRDS were divided into groups Ⅰ and Ⅱ randomly, prophylactic group were randomly divided into groups Ⅲ and Ⅳ, the means of administration in all patients was through tracheal tube. Neonates in group Ⅰ and Ⅲ, were given curosurf in several times with different posture, group Ⅱ and IV were given in one time with supine position. Blood gas analysis, index of mechanical ventilation, the duration of mechanical ventilation, hours of oxygen requirement and hospitalization between Ⅰ and Ⅱ group, the incidence of NRDS between Ⅲ, and IV group were analyzed and compared before and after treatment. Results After treatment for 6 and 24 hours, the oxygenation and lung function of group Ⅰ and Ⅱ improved respectively (P<0.05), the total times of assisted ventilation, Supplemental oxygen therapy and hospitalization were significantly decreased, the differences of those index were no significant between Ⅰ and Ⅱ group (P0.05), the incidence of NRDS have no different between Ⅲ and IV group. Conclusion Pulmonary surfactant is effective and safe for treating and prophylacting NRDS, and have no relationship with the means of administration.

The Expression of Cath D,SP-A,GLUT-1 of Bronchiogenic Carcinoma / 医学研究杂志

Objective To examine the expression of Cath D,SP-A and GLUT-1 in patients with bronchiogenic carcinoma.Methods A total of 41 patients were included in the study,10 of whom received the histological diagnosis of small cell lung cancer(SCLC).The other 28 were squamous cell carcinoma(SC) and 3 were inflammation.And all the samples were taken from the patients′ tunica mucosa bronchiorum through bronchofibroscope,then we detected the cathepsin D,SP-A and GLUT-1 following SP immunohistochemistry.Results ①Cath D: 6 samples(60%) in group SCLC were negtive expression(-6),4(40%)were moderately positive(++4),4(14%) were negative(-4),2(7%) were positive(+2),8(28%) were moderately positive(++8) and 14(50%) were intensive positive(+++14) in the other group.SCLC was significant different from SC in expressing cathepsin D(P

Human Surfactant Protein-A(SP-A) Gene Locus Associated with Mycoplasma pneumoniae Pneumonia in Korean Children / 소아과

PURPOSE: Mycoplasama pneumoniae is a leading cause of pneumonia and exacerbates other respiratory conditions such as asthma. Surfactant protein A(SP-A) is involved in surfactant physiology and surfactant structure, and plays a major role in innate host defense and inflammatory processes in the lung. In this study, SP-A mediated mycoplasma cidal activity. The candidate-gene approach was used to study the association between the SP-A gene locus and Mycoplasama pneumoniae pneumonia in the genetically homogeneous Korean population. METHODS: PCR-cRFLP-based methodology was used to detect SP-A genotype. The forty nine children with Mycoplasama pneumoniae pneumonia were matched to 50 nomal neonates. RESULTS: The specific frequencies for the alleles of the SP-A1 and SP-A2 gene in the study population were:6A2=21 percent, 6A3=45 percent, 6A4=11 percent, 6A8=9 percent, 6A14=8 percent, 1A=11.3 percent, 1A0=38 percent, 1A1=12.7 percent, 1A2=9.2 percent, 1A5=15.5 percent, 1A7=2.9 percent, 1A8=4.9 percent, 1A9=2.2 percent, others=3.3 percent. The frequencies of specific genotypes such as 1A2 was higher than control group, significantly. CONCLUSION: 1A2 are susceptible factors for Mycoplasama pneumoniae pneumonia. We conclude that the SP-A gene locus(1A2) is an important determinant for predisposition to Mycoplasama pneumoniae pneumonia in children.

Association between the Human Surfactant Protein-A(SP-A) Gene Locus and Respiratory Distress Syndrome in Korean Neonates / 소아과

PURPOSE: Respiratory distress syndrome(RDS) is caused by a deficiency of pulmonary surfactant, which is a lipoprotein complex. Both low levels of surfactant protein A(SP-A) and SP-A alleles have been associated with RDS. However, the genes underlying susceptibility to RDS are insufficiently known. The candidate-gene approach was used to study the association between the SP-A gene locus and RDS in the genetically homogeneous Korean population. METHODS: A PCR-cRFLP-based methodology was used to detect SP-A genotype. Twenty four neonates with RDS were matched pairwise to those without RDS. RESULTS: The frequencies of specific genotypes such as 6A(2), 1A(0) were increased, but the frequency of specific 1A(2) genotype was increased in control group. 6A(2)/1A(0) were also increased in the RDS group. Infants who did not have RDS develop, despite prematurity and lack of steroid therapy, had a higher frequency of the 1A(2) allele than infants who had received steroid therapy and had RDS develop. However, infants who had received steroid therapy and had RDS develop had a higher frequency of the 1A(0) allele than infants who did not have RDS develop, despite prematurity and lack of steroid therapy. CONCLUSION: SP-A alleles/haplotypes are susceptible(6A(2), 1A(0), 6A(2)/1A(0)) or protective(1A(2)) factors for RDS. We conclude that the SP-A gene locus is an important determinant for predisposition to RDS in neonates