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.

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.

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.

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.

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.

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.

利伐沙班联合阿替普酶治疗急性肺栓塞对患者凝血功能及GRP78 GRP94表达的影响

目的:观察利伐沙班联合阿替普酶对急性肺栓塞患者凝血功能及葡萄糖调节蛋白78(GRP78)、葡萄糖调节蛋白94(GRP94)表达的影响。方法:选取2021年1月至2022年12月我院收治的104例急性肺栓塞患者为对象,采用简单随机法分为两组。所有患者均给予绝对卧床、止痛、抗感染、吸氧等常规治疗,常规组(n=52)加用阿替普酶治疗,联合组(n=52)加用利伐沙班联合阿替普酶治疗。统计两组出血事件发生率。检测两组凝血功能、血栓弹力图及GRP78、GRP94、肺动脉压、血气指标的差异。结果:两组活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)及血栓弹力图中α角、反应时间(R)治疗后较治疗前升高,联合组治疗前后APTT、PT及血栓弹力图中R、α角差值大于常规组(P<0.05)。两组纤维蛋白原(Fib)、D-二聚体(D-D)治疗后较治疗前降低,联合组治疗前后Fib、D-D差值大于常规组(P<0.05);两组血栓弹力图中凝血时间(K)治疗前后比较,差异无统计学意义(P>0.05)。两组GRP78、GRP94治疗后较治疗前降低,联合组治疗前后GRP78、GRP94差值大于常规组(P<0.05)。两组动脉血氧分压(PaO 2)治疗后较治疗前升高,联合组治疗前后PaO 2差值大于常规组(P<0.05);两组动脉血二氧化碳分压(PaCO 2)治疗后较治疗前降低,联合组治疗前后PaCO 2差值大于常规组(P<0.05)。两组出血事件发生率比较,差异无统计学意义(P>0.05)。结论:利伐沙班联合阿替普酶治疗急性肺栓塞可降低GRP78、GRP94的表达,改善凝血功能和血气指标。

首次复治菌阳肺结核合并糖尿病患者血清IAP、25(OH)D水平及对疗效的预测价值

目的探讨首次复治菌阳肺结核(TB)合并糖尿病(DM)患者血清免疫抑制酸性蛋白(IAP)、25-羟基维生素D[25(OH)D]表达变化及2者对治疗疗效的预测价值。方法选取本院2019年1月至2022年4月首次复治菌阳TB合并DM患者48例为实验组,另选同期单纯TB患者48例为对照组。测定并比较两组患者治疗前后血清IAP、25(OH)D水平;多因素Logistic回归分析影响菌阳TB合并DM患者痰菌阴转的可能因素;受试者工作特征(ROC)曲线评估IAP、25(OH)D对患者痰菌未转阴的预测价值。结果实验组痰菌阴转患者31例(64.58%)显著低于对照组痰菌阴转患者40例(83.33%)。治疗2个月后,实验组、对照组血清IAP均显著降低,25(OH)D水平均显著升高(P<0.05);且治疗2个月后实验组血清IAP水平显著低于对照组,25(OH)D水平显著高于对照组(P<0.05)。多因素Logistic回归分析显示,IAP高水平是首次复治菌阳TB合并DM患者痰菌未阴转的危险因素(P<0.05),25(OH)D高水平是首次复治菌阳TB合并DM患者痰菌未阴转的保护因素(P<0.05)。ROC曲线显示,IAP预测痰菌未阴转的AUC为0.719,25(OH)D预测痰菌未阴转的AUC为0.791,2者联合预测痰菌未阴转的AUC为0.871,明显高于2者单独诊断(Z_(联合vs IAP)=2.605、P=0.009;Z_(联合vs 25(OH)D)=2.408、P=0.016),且灵敏度、特异性分别为78.46%、82.86%。结论首次复治菌阳TB合并DM患者经治疗后血清IAP水平降低、25(OH)D水平升高,2者联合对菌阳TB合并DM患者痰菌未阴转具有一定预测价值。

肺结核患者血清IP-10、SOCS1及CA125表达意义及其与引发支气管狭窄的相关性分析

目的分析肺结核患者血清γ干扰素诱导蛋白10(IP-10)、细胞因子信号转导抑制物1(SOCS1)及糖类抗原125(CA125)表达意义及其与引发支气管狭窄的相关性。方法回顾性选择2021年1月至2023年1月河北省胸科医院收治的116例肺结核患者作为观察组,同期116名健康体检者作为对照组。根据观察组患者胸部影像学检查结果,分为重度组(n=26)和轻中度组(n=90);通过纤维支气管镜检查及活检,判断患者是否存在支气管狭窄,分为支气管狭窄组(n=42)与单纯肺结核组(n=74)。检测所有入选者血清IP-10、SOCS1及CA125水平,比较血清IP-10、SOCS1及CA125在对照组与观察组、不同严重程度的肺结核患者中的差异性;比较支气管狭窄组与单纯肺结核组第1秒用力呼气量(FEV1)、用力肺活量(FVC)、最大呼气峰流速(PEF);分析血清IP-10、SOCS1及CA125与肺结核患者肺功能相关指标及其并发支气管狭窄的相关性。采用受试者工作特征(ROC)曲线分析血清IP-10、SOCS1及CA125水平预测肺结核患者发生支气管狭窄的效能。结果观察组血清IP-10、CA125水平分别为(95.84±12.58)ng/L、(1.89±0.86)U/mL,均高于对照组[(71.25±5.63)ng/L、(0.74±0.23)U/mL],SOCS1水平为(165.32±7.95)μg/L,低于对照组[(252.54±24.71)μg/L],差异均有统计学意义(P<0.05)。重度组肺结核患者血清IP-10、CA125水平分别为(106.74±15.01)ng/L、(2.67±1.12)U/mL,均高于轻中度组[(89.72±8.16)ng/L、(1.45±0.60)U/mL],SOCS1水平为(154.12±6.07)μg/L,低于轻中度组[(200.75±15.83)μg/L],差异均有统计学意义(P<0.05)。支气管狭窄组FEV1、FVC、PEF均小于单纯肺结核组,差异均有统计学意义(P<0.05)。经Pearson相关性分析,肺结核患者FEV1、FVC、PEF与血清IP-10、CA125水平呈正相关(P<0.05),与SOCS1水平呈负相关(P<0.05)。经ROC曲线分析,血清IP-10、SOCS1联合CA125预测肺结核患者发生支气管狭窄的敏感度为89.12%,特异度为48.63%,曲线下面积为0.924。结论肺结核患者血清IP-10、CA125水平明显升高,SOCS1水平降低,与病情严重程度相关,其联合预测支气管狭窄具有较好的效能。

卡巴胆碱对失血性休克大鼠肺微血管内皮细胞功能的影响

目的 观察大鼠失血性休克时卡巴胆碱对肺微血管内皮细胞的作用。方法 将30只健康雄性SD大鼠(SPF级)按每组10只随机分为假休克组(SS组)、失血性休克组(HS组)、失血性休克+卡巴胆碱组(CBL组)。失血性休克动物模型按照Wiggers改良法制作,各组模型制备完毕后6 h,经右侧股动脉采血,检测肿瘤坏死因子-α(TNF-α)水平,取右肺下叶肺组织检测Src抑制的蛋白激酶C的底物(SSeCKS)、E-选择素蛋白质水平,取右肺下叶行透射电镜检查肺微血管内皮细胞超微结构。结果 SS组表达少量的TNF-α、SSeCKS、E-选择素,HS组和CBL组表达升高(P<0.05),与HS组相比,CBL组表达降低(P<0.05)。SS组肺微血管内皮细胞细胞膜表面光滑,细胞膜、细胞质、细胞核形态结构正常;HS组肺微血管内皮细胞出现细胞水肿、坏死和凋亡表现(细胞膜表面皱折、细胞膜表面凹凸不平、细胞器水肿、异染色质染色加深边集等);CBL组较SS组,细胞有所损伤,但好于HS组。结论 大鼠失血性休克时卡巴胆碱对肺微血管内皮细胞具有保护作用,也可通过抑制炎症细胞合成和释放炎症介质减轻对血管内皮细胞的损伤。

老年重症肺炎患者血清4-HNE、APC、sCD163预测预后不良的价值

目的探讨老年重症肺炎(SP)患者血清4-羟基壬烯醛(4-HNE)、活化蛋白C(APC)、可溶性血红蛋白清道夫受体163(sCD163)对预后不良的预测价值。方法选取2020年8月至2022年8月新乡医学院第一附属医院收治的200例老年SP患者纳入SP组,另选取同期、同年龄段200例老年普通肺炎患者纳入普通肺炎组。比较两组患者和SP组不同预后患者的血清4-HNE、APC、sCD163水平,并采用Pearson法分析SP组患者血清4-HNE、APC、sCD163水平与肺部感染评分(CPIS评分)的相关性,采用Logistic回归分析老年SP患者死亡的影响因素,采用受试者工作特性曲线(ROC)分析各指标对预后情况的预测效能。结果SP组患者的血清4-HNE、sCD163水平分别为(21.27±4.02)mg/L、(154.27±56.34)pg/mL,明显高于普通肺炎组的(15.63±3.49)mg/L、(112.17±37.59)pg/mL,APC水平为(25.47±5.06)pmol/L,明显低于普通肺炎组的(30.12±6.14)pmol/L,差异均具有统计学意义(P<0.05);经Pearson法分析结果显示,入院时SP患者的血清4-HNE、sCD163水平与CPIS评分呈正相关(r=0.754、0.723,P<0.05),APC水平与之呈负相关(r=-0.695,P<0.05);入院3 d、7 d后,死亡组患者的血清4-HNE分别为(23.89±6.12)mg/L、(26.01±8.27)mg/L,明显高于生存组的(19.03±4.11)mg/L、(17.25±3.56)mg/L,sCD163水平分别为(182.34±60.33)pg/mL、(219.46±70.41)pg/mL,明显高于生存组的(137.83±30.24)pg/mL、(120.74±25.17)pg/mL,APC水平分别为(23.04±4.89)pmol/L、(20.73±4.25)pmol/L,明显低于生存组的(27.42±4.09)pmol/L、(29.76±4.14)pmol/L,差异均具有统计学意义(P<0.05);Logistic回归分析结果显示,入院3 d、7 d后,血清4-HNE(>20.32 mg/L、>19.57 mg/L)、sCD163(>149.63 pg/mL、>146.90 pg/mL)是老年SP患者治疗28 d后死亡的危险因素,APC(>26.26 pmol/L、>27.37 pmol/L)是其保护因素(P<0.05);ROC分析结果显示,入院3 d后血清各指标水平联合预测死亡的曲线下面积(AUC)为0.910(95%CI:0.861~0.946),最佳预测敏感度、特异度分别为81.13%、86.39%,入院7 d后联合预测死亡的AUC为0.922(95%CI:0.876~0.955),最佳敏感度、特异度分别为90.57%、84.35%。结论血清4-HNE、APC、sCD163水平与老年SP发生、发展相关,各指标水平与CPIS评分均具有一定相关性,联合检测对老年SP患者预后情况具有一定预测价值,可作为临床评估肺部感染程度及预后的辅助指标。

血清IL-8、ESM-1、VAP-1在慢性阻塞性肺疾病临床诊断及病情评估中的应用

目的探讨慢性阻塞性肺疾病(COPD)患者血清白细胞介素-8(IL-8)、内皮特异性分子-1(ESM-1)、血管黏附蛋白-1(VAP-1)表达水平,分析其与病情程度相关性及其对COPD的诊断价值。方法选取2021年11月至2022年8月郑州大学第一附属医院收治的153例COPD患者为研究对象,其中COPD稳定期42例(设为SCOPD组)、COPD急性加重期111例(设为AECOPD组),同时选取同期于医院体检的健康志愿者51例为对照组。比较两组临床资料及血清IL-8、ESM-1、VAP-1水平。对比不同病情程度患者血清IL-8、ESM-1、VAP-1水平。分析血清各指标与肺功能、生化指标、病情程度相关性。评价血清各指标对SCOPD、AECOPD的诊断价值。结果AECOPD组、SCOPD组血清IL-8、ESM-1、VAP-1水平高于对照组,且AECOPD组高于SCOPD组(P<0.05);IL-8、ESM-1、VAP-1与生化指标、COPD评估测试表(CAT)、病情程度呈正相关,与肺功能呈负相关(P<0.05);血清各指标联合诊断SCOPD与AECOPD的曲线下面积(AUC)大于单独指标诊断(P<0.05)。结论血清IL-8、ESM-1、VAP-1与COPD病情严重程度相关,联合检测其水平对COPD具有一定诊断价值,可能作为疾病诊断、病情评估的重要指标。

COPD急性加重期患者外周血单个核细胞SOCS-1、TLR4 mRNA及血清cTnT、尿酸水平变化分析

目的探讨慢性阻塞性肺疾病(COPD)急性加重期患者外周血单个核细胞中细胞因子信号抑制蛋白-1(SOCS-1)、Toll样受体4(TLR4)mRNA水平及血清心肌肌钙蛋白T(cTnT)、尿酸水平变化。方法收集COPD急性加重期(组)患者70例,COPD稳定期(组)患者40例,对照组健康志愿者40名。检测外周血单个核细胞SOCS-1、TLR4 mRNA水平及血清cTnT、尿酸浓度;行肺功能检查并记录相关指标(FEV1、FEV1%、FEV1/FVC%)。对COPD急性加重期患者进行1 a随访,分为预后不良组和预后良好组。对外周血单个核细胞SOCS-1、TLR4 mRNA水平、血清cTnT、尿酸浓度行Pearson相关性分析,并对COPD急性加重期患者预后评估价值进行ROC曲线分析。结果COPD急性加重期组SOCS-1 mRNA表达水平明显低于COPD稳定期组、对照组,TLR4 mRNA水平及血清cTnT、尿酸浓度明显高于COPD稳定期组和对照组(均P<0.01)。COPD急性加重期组FEV1、FEV1%、FEV1/FVC%明显低于COPD稳定期组和对照组(P<0.05)。COPD急性加重期患者FEV1/FVC%与外周血单个核细胞SOCS-1 mRNA表达水平呈正相关关系(P<0.01),与外周血单个核细胞TLR4 mRNA水平及血清cTnT、尿酸浓度呈负相关关系(P<0.01)。预后不良组SOCS-1 mRNA水平明显低于预后良好组,TLR4 mRNA水平及血清cTnT、尿酸浓度明显高于预后良好组(P<0.05)。外周血单个核细胞SOCS-1、TLR4 mRNA水平及血清cTnT、尿酸联合检测对COPD急性加重期患者预后具有较高的评估价值。结论COPD急性加重期患者SOCS-1低表达,TLR4、cTnT、尿酸高表达,且与肺功能水平密切相关,联合检测对患者预后具有较高的评估价值。

lncSIL通过EZH2/P21/CDK6信号通路负向调控TGF-β1诱导的肺泡上皮细胞间质转化

目的研究在转化生长因子β1(TGF-β1)诱导肺泡上皮细胞间质转化(EMT)进程中lncSIL的作用及其相关信号通路。方法采用Western blot法研究沉默lncSIL后对TGF-β1诱导EMT进程中细胞标志蛋白E-钙黏蛋白(E-cad)、α-平滑肌肌动蛋白(α-SMA)和Ⅰ型胶原蛋白(ColⅠ)表达的影响;通过RNA pulldown分析lncSIL相互作用蛋白,并检测过表达或沉默lncSIL后对其靶基因组蛋白赖氨酸N-甲基转移酶(EZH2)以及下游因子P21蛋白(P21)和细胞周期蛋白依赖性激酶6(CDK6)表达的影响,并结合流式细胞术分析lncSIL对细胞周期进程的作用。结果沉默lncSIL后,间质细胞标志蛋白α-SMA和Col I表达升高,肺泡上皮细胞标志蛋白E-cad表达下降;RNA pulldown实验结果显示EZH2是与lncSIL相互作用的靶蛋白,并且沉默lncSIL后EZH2表达升高,其下游基因P21表达下调,CDK6表达上调,同时S期细胞的数量显著升高;过表达lncSIL时,EZH2与CDK6表达下调,P21表达上调,同时S期细胞的数量明显降低。结论lncSIL通过负向调控EZH2/P21/CDK6信号通路抑制细胞周期进程进而抑制TGF-β1诱导的肺泡上皮细胞向间质转化。

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.