Establishment of Surfactant-associated Protein A Suicide Gene System and Analysis of Its Activity

Summary： Alveolar epithelial type II （AT II） cells are essential for lung development and remodeling, as they are precursors for type I cells and also produce other non-repair cells （fibroblasts）. Progenitor ceils are believed to possess capability of multi-potent transdifferentiation, which is closely related to the niche, suggesting the importance of establishment of a lung progenitor cell niche model. We hypothesized that pulmonary surfactant-associated protein A （SPA） suicide gene system would cause AT II cell to kill itself through apoptosis and leave its niche. In vitro, the recombinant adeno-associated virus vectors-SPA-thymidine kinase （rAAV-SPA-TK） system was established to get targeted apoptotic AT II cells. The apoptosis of AT II cells was detected by using MTT. The results showed that cloned SPA gene promoter had specific transcriptional activity in SPA high expression cells, and SPA high expression cells （H441） transfected with TK gene had higher sensitivity to ganciclovir （GCV） than SPA low expression cells （A549）. In vivo, increased apoptosis of AT II cells induced by GCV in rAAV-SPA-TK system was observed by TUNEL. Finally, the successful packaging and application of rAAV-SPA-TK system provide experimental basis to get specific lung progenitor cell （AT II） niche in vitro and in vivo.

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.

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.

Discordantly Elevated Erythrocyte Sedimentation Rate (ESR) and Depressed C-Reactive Protein (CRP) Values in Early Diagnosis of Pulmonary Tuberculosis Patients in Maiduguri, Nigeria

Background: ESR and CRP measurements reflect different aspects of systemic inflammation. Generally, they are either elevated or depressed at the same time. This study was aimed at evaluating the clinical ability of these markers in the early diagnosis of pulmonary tuberculosis. Materials and Methods: A total of 50 (male 39, female 21) patients who tested positive to Acid Alcohol Fast Bacilli (AAFB) were studied. ESR and CRP values were estimated using standard procedures. Results: The mean ESR value among the AAFB positive patients was 53.16 ± 4.92 mm/hr while the CRP value was 0.273 ± 0.035 mg/L. Gender and age were not found to have any influence on the ESR and CRP values. No relationship was found to exist between ESR and CRP (r = 0.17;p = 0.235) and age (r = 0.125;p = 0.388). Conclusion: A moderately elevated ESR and low CRP values exist at the early diagnosis of tuberculosis. There is no correlation between ESR and CRP at the onset of tuberculosis;hence CRP cannot be used as a screening tool for early diagnosis of tuberculosis.

Expression of Heat Stress Protein 70 mRNA in Patients with Chronic Obstructive Pulmonary Disease and Its Significance

The effects of cigarette smoke extract (CSE) on the expression of heat stress protein 70 (Hsp70) in human bronchi smooth muscle cells were investigated in vitro, and the changes in Hsp70 mRNA in the patients with chronic obstructive pulmonary disease and their significance were explored. Human bronchi smooth muscle cells were cultured with CSE at the different concentrations. The expression of Hsp70 mRNA and Hsp70 was detected by reverse translation-polymerase chain reaction (RT-PCR) and Western blotting respectively. Levels of Hsp70 mRNA and Hsp70 in lymphocytes from 20 patients with COPD and 20 healthy smoking control subjects were measured by RT-PCR and Western blotting. The results showed the expression of both Hsp70 mRNA and Hsp70 was decreased conformably in human bronchi smooth muscle cells treated with CSE at certain concentration in vitro. The A values of the Hsp70 mRNA expression were 0.24±0.11 and 0.42±0.13 respectively in COPD patients and healthy smoking controls with the difference being significant (P<0.01). There was also significant difference in the A values of the Hsp70 expression between COPD patients and healthy smoking controls (20.9±9.9 vs 44.8±15.3, P<0.01). The levels of Hsp70 mRNA had strongly positive correlation with Hsp70 protein (r = 0.85, P<0 01). It was suggested that the expression of Hsp70 mRNA was in concordance with the expression of Hsp70, which could provide a basis on the study of Hsp70 gene regulation and Hsp70 gene in the development of COPD.

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.

Forkhead box protein A2 and T helper type 2-mediated pulmonary inflammation

The transcription factor forkhead box protein A2(FOXA2, also known as hepatocyte nuclear factor 3β or transcription factor 3β), has been found to play pivotal roles in multiple phases of mammalian life, from the early development to the organofaction, and subsequently in homeostasis and metabolism in the adult. In the embryonic development period, FOXA2 is require d for the formation of the primitive node and notochord, and its absence results in embryonic lethality. Moreover, FOXA2 plays an important role not only in lung development, but also in T helper type 2(Th2)-mediated pulmonary inflammation and goblet cell hyperplasia. In this article, the role of FOXA2 in lung development and Th2-mediated pulmonary inflammation, as well as in goblet cell hyperplasia, is reviewed. FOXA2 deletion in airway epithelium results into Th2-mediated pulmonary inflammation and goblet cell hyperplasia in developing lung. Leukotriene pathway and signal transducers and activators of transcription 6 pathway may mediate this inflammation through recruitment and activation of denditric cell during lung developments. FOXA2 is a potential treatment target for lung diseases with Th2 inflammation and goblet cell hyperplasia, such as asthma and chronic obstructive pulmonary disease.

C-Reactive Protein as a Triage Test in Guiding Who Should Get a Confirmatory Test for Pulmonary Tuberculosis Diagnosis among Adults: A Case-Control Proof-of-Concept Study from Urban Tanzania

Background: The current screening tools for tuberculosis (TB) are inadequate resulting in insufficient TB case detection and continued community transmission of TB. As the world is geared into finding missing TB cases, new strategies are called for to aid in rapid identification of TB cases. This study aimed to evaluate the role C-reactive protein (CRP) in triaging patients to get a definitive test for active pulmonary TB diagnosis in urban Tanzania. Methods: A case-control study was conducted among pulmonary TB (PTB) patients and contacts without active PTB. The diagnosis of PTB was performed using GeneXpert MTB/RIF assay and culture. Blood was collected from cases and controls for measuring CRP levels during recruitment. We compared socio-demographic characteristics, clinical and laboratory parameters obtained during recruitment and performed diagnostic accuracy analyses for CRP. Results: Out of all 193 study participants who were involved in final analysis, 147 (76.2%) were males. Pulmonary TB cases had significantly lower median BMI than controls (median 17.4 kg/m2 [IQR: 15.8 - 19.2 kg/m2] vs., 24.9 kg/m2 [IQR: 22.1 - 28.5 kg/m2), p < 0.001). There was no statistical difference in prevalence of HIV between PTB cases and controls i.e., 13.33% vs., 11.7%, p = 0.48. CRP was significantly higher in PTB cases vs., controls (median 67.8 mg/L, [IQR: 36.5 - 116.9 mg/L] vs., 1.55 mg/L, [IQR: 0.59 - 6.0 mg/L], p = 0.003). Furthermore, CRP at cut-off ≥10 mg/L was associated with best combination of sensitivity, specificity and area under the curve of 89.9%, 95% CI: 82.2 - 95.0, 80.9%, CI: 71.4 - 88.2 and 0.85, 95% CI: 0.80 - 0.90 respectively. A multivariate logistic regression model adjusted for fever, night sweats and body mass index showed that CRP above 10 mg/L was significantly associated with PTB, aOR 5.2, 95% CI 1.2 - 22.8. Conclusions: CRP at cut-off ≥10 mg/L can be used to screen pulmonary TB. These findings can be used to improve TB screening algorithm by incorporating CRP in combination with TB symptoms to identify patients who need further confirmatory TB tests. However, additional prospective studies are required to support our findings and contribute into policy recommendations on use of CRP in a screening algorithm for pulmonary TB.

Effects of Huang Qi Wu Wu Decoction on Plasma Proteins in 70 Cases of Chronic Pulmonary Heart Disease

Simple immune agar diffusion test was used to assay the contents of 12 plasma proteins in 70 cases of chronic pulmonary heart disease treated by Huang Qi Wu Wu Decoction (黄芪五物汤), with the other 70 cases who were not given Huang Qi Wu Wu Decoction as the control group. The total clinical effective rate in the treatment group was 90.0%, while that in the control group was 75.7%, with a statistically significant difference between the two groups (P<0.05). In the treatment group, the levels of prealbumin, transferrin and fibronectin elevated obviously after treatment, and the contents of C-reactive protein, ceruloplasmin, haptoglobin, a 1-antitrypsin and a 1-acid glycoprotein decreased markedly (P<0.01). In the control group, only the levels of ceruloplasmin and C-reactive protein decreased significantly (P<0.05). It is shown that Huang Qi Wu Wu Decoction may enhance the therapeutic effects for pulmonary heart disease, regulate the metabolism of plasma proteins, and improve the life quality of the patients.

Diagnostic accuracy of C-reactive protein for bacterial infections in acute exacerbation of chronic obstructive pulmonary disease: A meta-analysis

Objective:The clinical diagnostic accuracy of C-reactive protein(CRP)for bacterial infections in acute exacerbation of chronic obstructive pulmonary disease(AECOPD)is still controversial.This study evaluated its accuracy through Meta-analysis.Methods:Studies on the diagnostic value of CRP for bacterial infections in AECOPD were searched form Web of Science,PubMed,Cochrane library,EMBASE,WANFANG DATA,CNKI and China Biology Medicine disc.The included studies were evaluated according to QUADAS-2 assessment tool.Stata 12.0 software was used for meta analyses to summarize the sensitivity and the specificity of the included studies,and the heterogeneity test was conducted.The symmetric receiver operating characteristic curves(SROC)was drawn and the area under the curve(AUC)was calculated,and the funnel plot was drawn to determine publication bias.Results:664 studies were initially identified,20 of which met the inclusion criteria(9 in English and 11 in Chinese).Meta-analysis results showed that the summary sensitivity and specificity of CRP in diagnosing bacterial infections in AECOPD were 0.84,95%CI(0.77-0.90)and 0.76,95%CI(0.67-0.82),respectively.The AUC of SROC was 0.87,95%CI(0.83-0.89).Conclusion:CRP has high accuracy,sensitivity and specificity in distinguishing AECOPD bacterial infections from non-bacterial infection.

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.

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.

基于HMGB1介导的肺动脉平滑肌细胞焦亡探讨复方葶苈子汤治疗COPD-PH的作用机制

目的研究高迁移率族蛋白B1(high mobility group box 1,HMGB1)介导的肺动脉平滑肌细胞焦亡对慢性阻塞性肺疾病相关性肺动脉高压(chronic obstructive pulmonary disease-associated pulmonary hypertension,COPD-PH)形成的影响,及复方葶苈子汤的干预机制。方法以CCK-8法检测大鼠肺动脉平滑肌细胞(pulmonary arterial smooth muscle cells,PASMCs)的活性,筛选出合适的香烟烟雾提取物(cigarette smoke extract,CSE)和脂多糖(lipopolysaccharide,LPS)干预浓度及时间用于建立细胞损伤模型。将对数生长期细胞分为对照组、CSE组、LPS组和CSE+LPS组,对照组加入细胞培养液培养细胞。CSE组加入含10%CSE的细胞培养液,LPS组加入含1μg/mL LPS的细胞培养液,CSE+LPS组加入含10%CSE和1μg/mL LPS的细胞培养液,培养细胞24 h后,采用CCK-8法检测细胞活性,实时荧光定量聚合酶链反应(real-time fluorescent quantitative PCR,qRT-PCR)检测细胞中mRNA表达,蛋白质印迹法(Western blot,WB)检测细胞中蛋白表达,酶联免疫吸附法(enzyme linked immunosorbent assay,ELISA)检测细胞上清液中炎症因子含量,流式细胞术检测细胞焦亡,透射电子显微镜观察细胞的超微结构。以CCK-8法检测PASMCs的活性,筛选出复方葶苈子汤含药血清和甘草酸的最佳干预浓度及时间。将对数生长期细胞分为正常组、模型组、含药血清组和抑制剂组,对照组加入细胞培养液培养细胞,模型组、含药血清组和抑制剂组加入含10%CSE和1μg/mL LPS的细胞培养液,培养细胞24 h后弃去原培养液。正常组和模型组孔中加入含10%空白血清的细胞培养液,含药血清组孔中加入含10%复方葶苈子汤含药血清的细胞培养液,抑制剂组孔中加入含150μg/mL甘草酸和10%空白血清的细胞培养液,再培养细胞24 h后,采用CCK-8法检测细胞活性,RT-PCR检测细胞中mRNA表达,WB检测细胞中蛋白表达,ELISA检测细胞上清液中炎症因子含量,流式细胞术检测细胞焦亡,透射电子显微镜观察细胞的超微结构。结果筛选出10%CSE和1μg/mL LPS用于建立细胞损伤模型,干预时间为24 h。CSE、LPS和CSE联合LPS可以使PASMCs活性下降;可以促进PASMCs中HMGB1、RAGE、Caspase-8和GSDMD mRNA表达,HMGB1、RAGE、pro Caspase-8、cleaved Caspase-8和GSDMD蛋白表达,促进PASMCs上清液中白细胞介素-1β(interleukin-1β,IL-1β)和白细胞介素-18(interleukin-18,IL-18)分泌,促进PASMCs焦亡发生。筛选出10%复方葶苈子汤含药血清和150μg/mL甘草酸用于细胞干预,干预时间为24 h。复方葶苈子汤含药血清可以使损伤PASMCs活性升高;可以抑制损伤PASMCs中HMGB1、RAGE、Caspase-8和GSDMD mRNA表达,HMGB1、RAGE、pro Caspase-8、cleaved Caspase-8和GSDMD蛋白表达,抑制损伤PASMCs上清液中IL-1β和IL-18分泌,抑制PASMCs焦亡发生。结论复方葶苈子汤可以通过抑制HMGB1表达,抑制Caspase-8介导的PASMCs焦亡,并抑制炎症级联反应,从而改善COPD-PH。

氧浓度变化对人肺动脉内皮细胞中ANGPTL8表达的影响

目的探讨氧浓度变化对肺动脉内皮细胞(HPAECs)中血管生成素样蛋白8(ANGPTL8)表达的影响,以及ANGPTL8在肺动脉高压(PH)中的作用和机制。方法低氧(1%)和高氧(85%)处理HPAECs,Western blot和PCR等检测ANGPTL8的表达,并分析内皮-间质转化(EndMT)及ERK信号通路的变化。同时,高氧处理新生大鼠,构建支气管肺发育不良(BPD)模型,观察肺组织中ANGPTL8蛋白表达及ERK信号通路的变化。结果低氧组HPAECs中ANGPTL8的蛋白表达显著升高,伴随ERK信号通路的抑制(P<0.05)。ANGPTL8促进低氧诱导的EndMT过程(P<0.05),沉默ANGPTL8可以部分逆转EndMT过程。高氧组HPAECs和大鼠肺组织中ANGPTL8蛋白表达降低,伴随ERK信号通路的激活(P<0.05)。结论HPAECs中ANGPTL8对氧浓度变化高度敏感,其表达的变化与ERK信号通路的活性状态密切相关,对PH的发展具有潜在的调控作用。

PCT、WBC联合CRP在ICU呼吸感染中的表达、诊断价值及与CPIS评分的相关性分析

目的分析降钙素原(PCT)、白细胞计数(WBC)联合C反应蛋白(CRP)在重症监护室(ICU)呼吸感染中的表达、诊断价值及与临床肺部感染评分(CPIS)的相关性。方法选取2019年3月至2024年6月涿州市医院ICU呼吸感染患者105例为观察组,另外选取于ICU未发生呼吸感染117例患者为对照组。通过Zybio-Q7型免疫定量分析仪对两组PCT水平进行检测,通过XT-4000i型白细胞分析仪对两组WBC水平进行检测,通过免疫比浊法对两组CRP水平进行检测。分析PCT、WBC、CRP的表达变化与ICU呼吸感染临床特征、CPIS评分的关系及对ICU呼吸感染的诊断价值。结果观察组入住ICU时间(>15 d)和机械通气时间(>7 d)的占比显著高于对照组(P<0.05)。与对照组比较,观察组PCT、WBC、CRP水平和CPIS评分升高,差异具有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,入住ICU时间>15 d(OR=4.087)、PCT(OR=6.543)、WBC(OR=2.652)和CRP(OR=8.964)为影响ICU呼吸感染发生的危险因素。PCT、WBC、CRP与CPIS评分之间Pearson相关性分析显示,PCT、CPIS评分之间正相关(r=0.925,P=0.001);WBC、CPIS评分之间正相关(r=0.739,P=0.001);CRP、CPIS评分之间正相关(r=0.948,P=0.001)。ROC曲线显示,三项联合对ICU呼吸感染的诊断价值高于PCT、WBC、CRP单项诊断(P=0.002)。结论PCT、WBC联合CRP对ICU呼吸感染的诊断价值较高,且与CPIS评分呈正相关,因此上述指标可为ICU呼吸感染的早期诊断提供可靠依据。

IL-6、PCT、CRP及WBC与老年腹部手术患者术后肺部感染的相关性

目的研究血白细胞介素-6(IL-6)、降钙素原(PCT)、C反应蛋白(CRP)及白细胞计数(WBC)与老年腹部手术后早期肺部感染的相关性。方法收集2023年1月至2023年12月濮阳市中医医院收治的45例老年腹部手术后早期肺部感染患者作为感染组,另按1∶2比例抽取同期行腹部手术但术后早期未出现肺部感染的90例作为未感染组,所有病例术后次日清晨均采集血样完成IL-6、PCT、CRP、WBC检测,比较感染组与未感染组上述指标差异,分析早期肺部感染患者病原菌分布,比较不同感染严重程度患者上述指标的差异,分析以上各指标与肺部感染严重程度的关系,并应用受试者工作曲线(ROC)分析以上参数诊断老年腹部手术后早期肺部感染的效能。结果腹部手术后早期肺部感染病原菌分布主要以革兰阴性菌(77.78%)为主,其中铜绿假单胞菌所占比例最高(53.33%,其次为大肠埃希菌(15.56%);革兰阳性菌(17.78%)中金黄色葡萄球菌所占比例最高(11.11%);真菌占4.44%,均为白假丝酵母菌;感染组术后次日清晨血IL-6、PCT、CRP、WBC水平均高于未感染组,差异均有统计学意义(P<0.05);不同严重程度肺部感染患者术后次日各实验室指标比较差异有统计学意义,随感染严重程度的上升,IL-6、PCT、CRP、WBC水平上升,差异均有统计学意义(P<0.05);IL-6、PCT、CRP、WBC均与临床肺部感染评分(CPIS)呈正相关,差异均有统计学意义(r=0.716、0.765、0.725、0.735,P<0.05);IL-6、PCT、CRP、WBC联合检测诊断腹部手术早期肺部感染的曲线下面积(AUC)值高于单项检测,差异均有统计学意义(P<0.05)。结论IL-6、PCT、WBC及CRP对老年腹部外科术后早期肺部感染皆有一定的诊断价值,且联合检测诊断效能更高,可将其作为腹部外科术后早期肺部感染筛查的重要指标。

Iptakalim, a novel ATP-sensitive potassium channel opener, inhibits pulmonary arterial smooth muscle cell proliferation by downregulation of PKC-α

Iptakalim is a new ATP-sensitive potassium （KATp） channel opener, and it inhibits the proliferation of pulmonary arterial smooth muscle cells （PASMCs） and pulmonary vascular remodeling. However, the underlying mechanism remains unclear. In the present study, we found that iptakalim significantly decreased pulmonary artery pressure, inhibited pulmonary ariery remodeling and PKC-α overexpression in chronic hypoxia in a rat pulmonary hypertension model. Iptakalim reduced hypoxia-induced expression of PKC-α, and abolished the effect of hypoxia on PASMC proliferation significantly in a dose-dependent manner in vitro. Moreover, these effects were abol- ished by glibenclamide, a selective KArp channel antagonist. These results indicate that iptakalim inhibits PASMC proliferation and pulmonary vascular remodeling induced by hypoxia through downregulating the expression of PKC-α. Iptakalim can serve as a novel promising treatment for hypoxic pulmonary hypertension.

Hypoxia promotes pulmonary vascular remodeling via HIF-1α to regulate mitochondrial dynamics

Background Increasing research suggests that mitochondrial defect plays a major role in pulmonary hypertension(PH) pathogenesis. Mitochondrial dynamics and quality control have a central role in the maintenance of the cell proliferation and apoptosis balance. However, the molecular mechanism underlying of this balance is still unknown. Methods To clarify the biological effects of hypoxic air exposure and hypoxia-inducible factor-1α(HIF-1α) on pulmonary arterial smooth muscle cell(PASMC) and pulmonary arterial hypertension rats, the cells were cultured in a hypoxic chamber under oxygen concentrations. Cell viability, reactive oxygen species level, cell death, mitochondrial morphology, mitochondrial membrane potential, mitochondrial function and mitochondrial biosynthesis, as well as fission-and fusion-related proteins, were measured under hypoxic conditions. In addition, rats were maintained under hypoxic conditions, and the right ventricular systolic pressure, right ventricular hypertrophy index and right ventricular weight/body weight ratio were examined and recorded. Further, we assessed the role of HIF-1α in the development and progression of PH using HIF-1α gene knockdown using small interfering RNA transfection. Mdivi-1 treatment was performed before hypoxia to inhibit dynamin-related protein 1(Drp1). Results We found that HIF-1α expression was increased during hypoxia, which was crucial for hypoxia-induced mitochondrial dysfunction and hypoxia-stimulated PASMCs proliferation and apoptosis. We also found that targeting mitochondrial fission Drp1 by mitochondrial division inhibitor Mdivi-1 was effective in PH model rats. The results showed that mitochondrial dynamics were involved in the pulmonary vascular remodeling under hypoxia in vivo and in vitro. Furthermore, HIF-1α also modulated mitochondrial dynamics in pulmonary vascular remodeling under hypoxia through directly regulating the expression of Drp1. Conclusions In conclusion, our data suggests that abnormal mitochondrial dynamics could be a marker for the early diagnosis of PH and monitoring disease progression. Further research is needed to study the signaling pathways that govern mitochondrial fission/fusion in PH.

Protective effect of extracorporeal membrane pulmonary oxygenation combined with cardiopulmonary resuscitation on post-resuscitation lung injury

BACKGROUND: Cardiac arrest(CA) is a critical condition that is a concern to healthcare workers. Comparative studies on extracorporeal cardiopulmonary resuscitation(ECPR) and conventional cardiopulmonary resuscitation(CCPR) technologies have shown that ECPR is superior to CCPR. However, there is a lack of studies that compare the protective effects of these two resuscitative methods on organs. Therefore, we aim to perform experiments in swine models of ventricular fibrillation-induced CA to study whether the early application of ECPR has advantages over CCPR in the lung injury and to explore the protective mechanism of ECPR on the post-resuscitation pulmonary injury.METHODS: Sixteen male swine were randomized to CCPR(CCPR;n=8;CCPR alone) and ECPR(ECPR;n=8;extracorporeal membrane oxygenation with CCPR) groups, with the restoration of spontaneous circulation at 6 hours as an endpoint. RESULTS: For the two groups, the survival rates between the two groups were not statistically significant(P>0.05), the blood and lung biomarkers were statistically significant(P<0.05), and the extravascular lung water and pulmonary vascular permeability index were statistically significant(P<0.01). Compared with the ECPR group, electron microscopy revealed mostly vacuolated intracellular alveolar type II lamellar bodies and a fuzzy lamellar structure with widening and blurring of the blood-gas barrier in the CCPR group.CONCLUSIONS: ECPR may have pulmonary protective effects, possibly related to the regulation of alveolar surface-active proteins and mitigated oxidative stress response postresuscitation.

Pachymic Acid Ameliorates Pulmonary Hypertension by Regulating Nrf2-Keap1-ARE Pathway

Objective:Pulmonary hypertension(PH)is a severe pulmonary vascular disease that eventually leads to right ventricular failure and death.The purpose of this study was to investigate the mechanism by which pachymic acid(PA)pretreatment affects PH and pulmonary vascular remodeling in rats.Methods:PH was induced via hypoxia exposure and administration of PA(5 mg/kg per day)in male Sprague-Dawley rats.Hemodynamic parameters were measured using a right ventricular floating catheter and pulmonary vascular morphometry was measured by hematoxylin-eosin(HE),a-SMA and Masson staining.MTT assays and EdU staining were used to detect cell proliferation,and apoptosis was analyzed by TUNEL staining.Western blotting and immunohistochemistry were used to detect the expression of proteins related to the Nrf2-Keapl-ARE pathway.