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.

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.

Increased CAP37 Expression in Stable Chronic Obstructive Pulmonary Disease

Objective Cationic antimicrobial protein of 37 kDa(CAP37),a neutrophil-derived protein originally identified for its antimicrobial activity,is now known to have many regulatory effects on host cells.However,its role in the pathogenesis of chronic obstructive pulmonary disease(COPD)has not been studied.We therefore investigated the expression of CAP37 in COPD and its effects on airway structural cells,including bronchial epithelial cells,smooth muscle cells,and fibroblasts.Methods CAP37 was detected in the lung tissue,sputum,and plasma of COPD patients and the control subjects,as well as in the neutrophils stimulated by cigarette smoke extract(CSE).BEAS-2B cells,human bronchial smooth muscle cells(HBSMCs),and MRC-5 cells were treated with CAP37 or an anti-CAP37 antibody plus CAP37.Interleukin(IL)-6 and IL-8 were detected in the BEAS-2B cells.The cell proliferation was analyzed in the HBSMCs.Collagens were also detected in the MRC-5 cells.Results The expression of CAP37 was increased in the lung tissue and sputum supernatant of the COPD patients compared with the control subjects.The sputum supernatant CAP37 levels were inversely correlated with the forced expiratory volume in the first second percentage predicted in COPD.CAP37 was induced by CSE stimulation in the peripheral blood neutrophils from healthy non-smokers.CAP37 induced expression of IL-6 and IL-8 in BEAS-2B cells,and collagen expression of lung fibroblasts(MRC-5 cells).However,CAP37 did not significantly alter the proliferation of the HBSMCs.Conclusion Our findings indicated that neutrophil-derived CAP37 may be involved in airway inflammation and fibrosis in COPD via affecting the bronchial epithelial cells,and fibroblasts,thus suggesting a possible role of CAP37 in the development and progression of COPD.

Effects of Suhuang Zhike Capsule on Pulmonary Function, Blood Gas Analysis Index, Serum PCT and CRP Expression in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease

OBJECTIVE: To observe the effects of Suhuang Zhike Capsule on pulmonary function, blood gas analysis index, serum PCT and CRP expression in patients with acute exacerbation of chronic obstructive pulmonary disease. METHODS: A total of 88 patients with acute exacerbation of chronic obstructive pulmonary disease admitted to the Department of Respiratory Medicine, Xuancheng People's Hospital of Anhui Province from December 2014 to December 2016 were randomly divided into the observation group and the control group, with 44 cases in each group. The control group was given routine clinical treatment, and the observation group was given Suhuang Zhike Capsule on the basis of the treatment method of the control group. After 7 days' treatment, the improvement of lung function indexes were observed and evaluated before and after treatment(forced expiratory volume in one second(FEV_1), forced expiratory volume occupancy in the 1^(st) second percentage of vital capacity(FEVl/FVC), peak expiatory flow(PEF)), blood gas analysis index(Arterial oxygen partial pressure(PaO_2) and arterial blood carbon dioxide partial pressure(PaCO_2), oxygenation index(OI)) and serum cytokine levels(procalcitonin(PCT) and C reactive protein(CRP). RESULTS: The total effective rate of the observation group was significantly higher than that of the control group(P < 0.05). The FEV_1, FEV_1/FVC and PEF in 2 groups were significantly increased after the treatment(P < 0.05), and the above lung function indexes in the observation group were significantly higher than the control group(P < 0.05). PaO_2 and OI were significantly increased after the treatment(P < 0.05), PaCO_2 was significantly decreased after the treatment(P < 0.05), and the improvement of above blood gas analysis indexes were significantly superior of the observation group than the control group(P < 0.05). The serum PCT and CRP levels in 2 groups were significantly decreased after the treatment(P < 0.05), and the improvement in the observation group were more significant than that in the control group(P < 0.05). CONCLUSION: Suhuang Zhike Capsule can inhibit serum inflammatory cytokine levels in patients with acute exacerbation of chronic obstructive pulmonary disease, improve blood gas analysis indicators, and improve lung functions.

Von Hippel-Lindau protein and respiratory diseases

Von Hippel-Lindau protein(p VHL) was first identified as a tumor suppressor gene as mutations in the VHL gene predispose individuals to systemic benign or malignant tumors and cysts in many organs, including renal cell carcinoma of the clear-cell type and hemangioblastoma. Although p VHL is best known to act as a component of ubiquitin protein ligase for the proteasomal degradation of hypoxia inducible factor(HIF)-α, p VHL also interacts with extracellular matrix proteins and cytoskeleton, regulating extracellular matrix assembly, cell signaling, and many other cellular functions. Recent studies suggest that p VHL contributes to many lung diseases, including pulmonary arterial hypertension, lung cancer, pulmonary fibrosis, and acute respiratory distress syndrome. Mutation or loss of function of p VHL activates HIF and induced expression of vascular endothelial growth factor, endothelin-1, and Fox M1, leading to pulmonary arterial hypertension. Loss of p VHL in lung cancer cells promotes epithelial-mesenchymal transition and cancer migration and invasion while decreasing lung cancer cell proliferation and colonization. In patients of idiopathic pulmonary fibrosis, elevated expression of p VHL induces expression of fibronectin/integrin α5β1/focal adhesion kinase signaling, resulting in fibroproliferation and fi-brosis. In alveolar epithelial cells, p VHL mediates Na, K-ATPase degradation in an HIF independent pathway, causing decreased edema clearance during hypoxia. These studies suggest that p VHL plays key roles in the pathogenesis of many lung diseases, and further investigations are warranted to elucidate the underlying molecular mechanisms.

The Clinical Value of NLR, D-D and CRP/ALB Ratio in the Diagnosis of Pulmonary Thromboembolism

Objective: To evaluate the clinical diagnostic value of C-reactive protein/albumin ratio (CAR), neutrophil/lymphocyte ratio (NLR) and D-dimer (D-D) in patients with pulmonary thromboembolism (PTE). Methods: We conducted a retrospective analysis comparing hematology and coagulation in 362 PTCA-confirmed PTE patients with the control group and analyzing their relationships with CAR, NLR, and D-D. Receiver operating characteristic curve (ROC) was used to analyze the diagnostic threshold, area under the curve (AUC), diagnostic sensitivity and specificity of CAR, NLR and D-D for PTE. Results: 1) CAR, NLR and D-D levels in PTE patients were 2.13 ± 2.08, 8.96 ± 1.94 and 9.69 ± 8.61 respectively, significantly higher than those in control group (CAR = 0.03 ± 0.01, t = 20.7736, P < 0.01;NLR = 1.76 ± 0.53, t = 2.4281, P < 0.05 and PTE = 0.20 ± 0.11, t = 3.0066, P < 0.01 respectively). 2) NLR was positively correlated with CAR (r = 0.2111, t = 4.0971, P < 0.01) and D-D (r = 0.1065, t = 2.0481, P < 0.05), but CAR was not correlated with D-D (r = 0.0975, P > 0.05). 3) The levels of HB, LY, PLT and AT in PTE patients were significantly lower than those in control group, while WBC, NE and FB were significantly higher than those in control group. 4) CAR was negatively correlated with Hb and AT (P all < 0.01), but positively correlated with WBC, NE, MO and FB (P all < 0.01). NLR was negatively correlated with LY and AT (P all < 0.01), but positively correlated with WBC, NE and FB (P all < 0.01). DD was negatively correlated with Hb and PLT (P all < 0.05), but positively correlated with WBC, NE and MO (P all < 0.01). Conclusion: The levels of Hb, LY, PLT and AT were significantly decreased in PTE patients, while WBC, NE and FB were significantly increased. CAR, NLR and D-D were highly expressed in PTE patients, and were closely correlated with Hb, AT and FB. Combined detection of CAR, NLR and D-D can improve the diagnostic value of PTE.