Low diastolic blood pressure and adverse outcomes in inpatients with acute exacerbation of chronic obstructive pulmonary disease: A multicenter cohort study / 中华医学杂志(英文版)

BACKGROUND@#Although intensively studied in patients with cardiovascular diseases (CVDs), the prognostic value of diastolic blood pressure (DBP) has little been elucidated in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This study aimed to reveal the prognostic value of DBP in AECOPD patients.@*METHODS@#Inpatients with AECOPD were prospectively enrolled from 10 medical centers in China between September 2017 and July 2021. DBP was measured on admission. The primary outcome was all-cause in-hospital mortality; invasive mechanical ventilation and intensive care unit (ICU) admission were secondary outcomes. Least absolute shrinkage and selection operator (LASSO) and multivariable Cox regressions were used to identify independent prognostic factors and calculate the hazard ratio (HR) and 95% confidence interval (CI) for adverse outcomes.@*RESULTS@#Among 13,633 included patients with AECOPD, 197 (1.45%) died during their hospital stay. Multivariable Cox regression analysis showed that low DBP on admission (<70 mmHg) was associated with increased risk of in-hospital mortality (HR = 2.16, 95% CI: 1.53-3.05, Z = 4.37, P <0.01), invasive mechanical ventilation (HR = 1.65, 95% CI: 1.32-2.05, Z = 19.67, P <0.01), and ICU admission (HR = 1.45, 95% CI: 1.24-1.69, Z = 22.08, P <0.01) in the overall cohort. Similar findings were observed in subgroups with or without CVDs, except for invasive mechanical ventilation in the subgroup with CVDs. When DBP was further categorized in 5-mmHg increments from <50 mmHg to ≥100 mmHg, and 75 to <80 mmHg was taken as reference, HRs for in-hospital mortality increased almost linearly with decreased DBP in the overall cohort and subgroups of patients with CVDs; higher DBP was not associated with the risk of in-hospital mortality.@*CONCLUSION@#Low on-admission DBP, particularly <70 mmHg, was associated with an increased risk of adverse outcomes among inpatients with AECOPD, with or without CVDs, which may serve as a convenient predictor of poor prognosis in these patients.@*CLINICAL TRIAL REGISTRATION@#Chinese Clinical Trail Registry, No. ChiCTR2100044625.

Clinical characteristics of severe coronavirus disease 2019 patients with chronic obstructive pulmonary disease / 中南大学学报(医学版)

OBJECTIVES@#Coronavirus disease 2019 (COVID-19) in elderly and patients with chronic respiratory diseases (COPD) had a poor prognosis. COPD is one of the most common chronic respiratory diseases. We explore the epidemiological characteristics of patients with severe COVID-19 with COPD patients in order to provide medical evidence for the prevention and treatment of severe COVID-19.@*METHODS@#We retrospectively analyzed the clinical baseline characteristics, treatment strategies, disease progression and prognosis of 557 severe COVID-19 patients admitted to the West Court of Union Hospital of Huazhong University of Science and Technology from January 29, 2020 to April 8, 2020.@*RESULTS@#A total of 465 patients with severe COVID-19 were enrolled in the study, including 248 (53.3%) males and 217 (46.7%) females. The median age of severe COVID-19 patients was 62.0 years, and 53 patients were complicated with COPD. Common symptoms at the onset included fever (78.5%), dry cough (67.1%), shortness of breath (47.3%) and fatigue (40.9%). Compared with non-COPD patients, patients with COPD had significantly lower levels of SpO2 in admission (90.0% vs 92.0%, P=0.014). In terms of laboratory examinations, patients with COPD had higher levels of C-reactive protein, interleukin-6, procalcitonin, total bilirubin, blood urea nitrogen, serum creatinine, lipoprotein (a), high-sensitivity troponin I, and D-dimer, while had lower levels of platelet counts, albumin and apolipoprotein AI. Severe COVID-19 patients with COPD had higher Sequential Organ Failure Assessment scores [3.0(2.0, 3.0) vs 2.0(2.0, 3.0), P=0.038] and CURB-65 score [1.0(1.0, 2.0) vs1.0(0.0, 1.0), P<0.001], and a higher proportion of progressing to critical illness (28.3% vs 10.0%, P<0.001) with more complications [e.g. septic shock (15.1% vs 6.1%, P=0.034)], had higher incidence rates of antibiotic therapies (90.6% vs 77.2%, P=0.025), non-invasive (11.3% vs 1.7%, P<0.001) and invasive mechanical ventilation (17.0% vs 8.3%, P=0.039), ICU admission (17.0% vs 7.5%, P=0.021) and death (15.1% vs 6.1%, P=0.016). Cox proportion hazard model was carried out, and the results showed that comorbid COPD was an independent risk factor for severe COVID-19 patients progressing to critical type, after adjusting for age and gender [adjusted hazard ratio (AHR)=2.38(1.30-4.37), P=0.005] and additionally adjusting for chronic kidney diseases, hypertension, coronary heart disease [AHR=2.63(1.45-4.77), P<0.001], or additionally adjusting for some statistically significant laboratory findings [AHR=2.10(1.13-3.89), P=0.018].@*CONCLUSIONS@#Severe COVID-19 patients with COPD have higher levels of disease severity, proportion of progression to critical illness and mortality rate. Individualized treatment strategies should be adopted to improve the prognosis of severe COVID-19 patients.

Genome-wide analysis identify novel germline genetic variations in ADCY1 influencing platinum-based chemotherapy response in non-small cell lung cancer

To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma (NSCLC), we performed a two-cohort of genome-wide association studies (GWAS), including 34 for WES-based and 433 for microarray-based analyses, as well as two independent validation cohorts. After integrating the results of two studies, the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples, and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments. We found that a total of 68 variations were significant at P < 1 × 10-3 in cohort 1 discovery stage, of which 3 SNPs were verified in 262 independent samples. A total of 541 SNPs were significant at P < 1 × 10-4 in cohort 2 discovery stage, of which 8 SNPs were verified in 347 independent samples. Comparing the validated SNPs in two GWAS, ADCY1 gene was verified in both independent studies. The results of fine-mapping showed that the G allele carriers of ADCY1 rs2280496 and C allele carriers of rs189178649 were more likely to be resistant to platinum-based chemotherapy. In conclusion, our study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients.

Effect of Brucea javanica oil emulsion on proliferation, migration and autophagy of non-small cell lung cancer A549 cells and the underlying mechanisms / 中南大学学报(医学版)

To investigate the effect of Brucea javanica oil emulsion on proliferation, migration and autophagy of non-small cell lung cancer A549 cells.
 Methods: First, A549 cells were divided into a control group and a low, medium or high dose of Brucea javanica oil emulsion groups (0, 2.5, 5.0 or 10.0 mg/mL); then, the cells were divided into a 3-MA+Brucea javanica oil emulsion group and a Brucea javanica oil emulsion group in the presence or absence of 3-methyl adenine (3-MA). Cell counting kit-8 (CCK-8) and clone formation assay were used to detect cell proliferation, while the wound scratch and Transwell assay were used to measure cell migration. Cell immunofluorescence and Western blot were used to analyze autophagy.
 Results: Compared with the control group, the numbers of cell proliferation and colony-formation, the relative cell migration rate and numbers of trans-membrane cells were reduced in a dose-dependent manner in the Brucea javanica oil emulsion groups (all P<0.05). Meanwhile, compared with the control group, the aggregation of microtubule associated protein 1 light chain3 (LC3) green fluorescence and the LC3-II/LC3-I ratios were increased, while p62 level was decreased (all P<0.05) in the high dose group. Compared with the Brucea javanica oil emulsion group (5.0 mg/mL), the cell proliferation, numbers of cell clone formation, cell migration rate and numbers of Transwell transmembrane cells were increased in the 3-MA+Brucea javanica oil emulsion group (all P<0.05).
 Conclusion: Brucea javanica oil emulsion can promote the autophagy of non-small cell lung cancer A549 cells and inhibit the cell proliferation and migration.

A fatal case of severe Nocardia farcinica pneumonia and literature review of 25 cases / 中国感染控制杂志

Nocardia is a genus of gram-positive,weakly acid-fast,filamentous aerobic actinomycetes,which mainly causes infection in immunocompromised persons. We reported a successfully treated fatal case of severe pneumonia caused by Nocardia farcinica in a hospital,then reviewed 25 domestic and abroad case reports about nocardiosis combined with severe pneumonia occurred since 2006,so as to improve health care workers'cognition on clinical manifestations,image features,pathogenic characteristics,and diagnostic and treatment schemes of se-vere pneumonia caused by Nocardia farcinica.

Clinical comparative analysis for pulmonary histoplasmosis and progressive disseminated histoplasmosis / 中南大学学报(医学版)

To compare clinical features, diagnosis and therapeutic effect between pulmonary histoplasmosis and progressive disseminated histoplasmosis.
 Methods: A retrospective analysis for 12 cases of hospitalized patients with histoplasmosis, who was admitted in Xiangya Hospital, Central South University during the time from February 2009 to October 2015, was carried out. Four cases of pulmonary histoplasmosis and 8 cases of progressive disseminated histoplasmosis were included. The differences of clinical features, imaging tests, means for diagnosis and prognosis were analyzed between the two types of histoplasmosis.
 Results: The clinical manifestations of pulmonary histoplasmosis were mild, such as dry cough. However, the main clinical symptoms of progressive disseminated histoplasmosis were severe, including recurrence of high fever, superficial lymph node enlargement over the whole body, hepatosplenomegaly, accompanied by cough, abdominal pain, joint pain, skin changes, etc.Laboratory examination showed pancytopenia, abnormal liver function and abnormal coagulation function. One pulmonary case received the operation of left lower lung lobectomy, 3 cases of pulmonary histoplasmosis and 6 cases of progressive disseminated histoplasmosis patients were given deoxycholate amphotericin B, itraconazole, voriconazole or fluconazole for antifungal therapy. One disseminated case discharged from the hospital without treatment after diagnosis of histoplasmosis, and 1 disseminated case combined with severe pneumonia and active tuberculosis died ultimately.
 Conclusion: As a rare fungal infection, histoplasmosis is easily to be misdiagnosed. The diagnostic criteria depends on etiology through bone marrow smear and tissues biopsy. Liposomeal amphotericin B, deoxycholate amphotericin B and itraconazole are recommended to treat infection for histoplasma capsulatum.

Effect of chronic intermittent hypoxia on the expression of CXC chemokine ligand-10 in rat liver and the interventional effect of N-acetylcysteine / 中南大学学报(医学版)

OBJECTIVE@#To explore the effect of chronic intermittent hypoxia (CIH) on liver injury and to examine the expression of liver CXC chemokine ligand-10 (CXCL10) in the rats, and to explore the effect of N-acetylcysteine (NAC).
@*METHODS@#A total of 21 male SD rats were randomly divided into a control group, a CIH group and a CIH+NAC group (n=7 in each group). The control group exposed to normal gaseous environment, the other 2 groups were exposed to CIH for 5 weeks (8 h/d); the control group and the CIH group were given daily saline lavage, the CIH+NAC group daily received NAC solution. After the end of 5 weeks, the rats were killed, and the MDA content and SOD activity in rat liver tissues were detected. The liver sections were stained with hematoxylin-eosin (HE) and the liver pathology was observed. The expression of CXCL10 in the liver tissues was detected by immunohistochemical method.
@*RESULTS@#Compared with the control group, the MDA levels in rat liver tissues were increased (P<0.05), and the SOD levels were decreased (P<0.05) in the CIH group and the CIH+NAC group. Compared with the CIH group, the SOD levels in the rat liver tissues were increased (P<0.05), and the MDA levels were decreased in the CIH+NAC group. Compared with the control group, the hepatic steatosis and inflammatory reactions were more severe in the CIH group and the CIH+NAC group (both P<0.01). Compared with the CIH group, the hepatic steatosis and inflammatory reactions were reduced in the CIH+NAC group (P<0.05). The liver damage in the CIH+NAC group was less than that in the CIH group (P<0.05). Compared with the control group, the CXCL10 expression in the CIH group and the CIH+NAC group was increased (both P<0.01). The CXCL10 expression in the CIH+NAC group was down-regulated compared with that in the CIH group (P<0.01).
@*CONCLUSION@#CIH can lead to liver injury and induce CXCL10 expression in rat liver tissues. The NAC can alleviate rat liver oxidative stress and inflammation caused by CIH, and in turn to improve the liver injury in rats.

Multidrug-resistant Acinetobacter Baumannii infection in Intensive Care Unit: A retrospective analysis / 中南大学学报(医学版)

OBJECTIVE@#To analyze the clinical characteristics of patients with bloodstream Acinetobacter baumannii infection in Intensive Care Unit (ICU).
@*METHODS@#Eighty-three ICU patients with bloodstream Acinetobacter baumannii infection from January 2012 to March 2015 were retrospectively analyzed, including infection-related risk factors, drug-resistant bacteria, treatments and prognosis.
@*RESULTS@#Among 83 patients, 60 patients (72.29%) were male, 23 (27.71%) were female. The youngest patient was 40 days old, the oldest was 92 years old, the age was (46.23±19.22) years old. In total, there were 20 patients (24.10%) with plural bacterial infection in blood, 60 (72.29%) with more than 3 kinds of disorders, 52 patients suffered homologous bacterial infection in blood and other organs. Among these cases, lower respiratory tract had the highest percentage of homologous bacteria (29 cases), followed by catheter (11 cases), wound secretion (8 cases), cerebrospinal fluid (3 cases) and ascites (1 case). The risk factors of bloodstream infection by Acinetobacter baumannii included catheterization, serious primary disease and basic disease, usage of corticosteroids, surgery and invasive operation and so on. Acinetobacter baumannii were highly resistant. Most of them were multi-drug resistance, and some were pan-drug resistance. It showed more than 80% drug resistant rate to antibiotics except sulbactam, cefopcrazone and amikacin. Among 83 patients, 55 cases (66.26%) were dead, 25 cases (30.12%) were improved and 3 cases (3.62%) were cured.
@*CONCLUSION@#Acinetobacter baumannii are highly and multidrug-resistant to commonly used antibiotics. Patients in ICU suffering serious basic diseases should be shorten hospitalization time, restricted the use of breathing machine and immunosuppressant. It must carry out disinfection for invasive operation to reduce the risk of bloodstream infections, and the abuse of antibiotics must be avoided to slow bacteria resistance.

Role of nerve growth factor in differentiation of dendritic cells / 中南大学学报(医学版)

OBJECTIVE@#To explore the effect of nerve growth factor (NGF) on the  differentiation of murine bone marrow-derived dendritic cells (DCs) in vitro.
@*METHODS@#The bone marrow cells of femur and tibia from healthy C57B -L/6 mice were isolated and divided into 4 groups: a phosphate buffered saline (PBS) group (PBS group), a NGF group, a granulocyte monocyte colony stimulating factor (GM-CSF) plus interleukin 4 (IL-4) group (GM-CSF+IL-4 group), and a GM-CSF plus IL-4 and NGF group (n=6 in each group). The positive rate of CD11c+ and the proportion of CD8a- were compared at the 7th day among the different groups by flow cytometry. The immature DCs were acquired by classic methods with GM-CSF and IL-4. The purified DCs were obtained by magnetic bead positive selection for CD11c+ cells. The immature DCs were divided into 4 groups: a PBS group, a NGF group, a LPS group, and a NGF+LPS group (n=6 in each group), which were incubated with PBS, NGF, LPS and NGF+LPS, respectively. Cytokine levels of IL-6, IL-10 and IL-12 were detected by ELISA after 24 hours..
@*RESULTS@#1) the percentage of CD11c+ DCs in the NGF group were more than that in the PBS group, and lower than that in the the GM- CSF+IL-4 group (both P0.05). CD8a- DCs were dominant in these four groups; 2) NGF could further up-regulate the LPS-induced cytokine secretion from DCs, such as IL-6, IL-10, and IL-12 (all P<0.05), but NGF alone had no such effect (all P<0.05).
@*CONCLUSION@#NGF can promote the murine bone-marrow cells differentiation into CD11c+ DCs, with CD8a-subset; NGF could enhance LPS-induced cytokine secretion from DCs (IL-6, IL-10 and IL-12).

Review of 2 cases of severe infection with pulmonary Strongyloides stercoralis / 中南大学学报(医学版)

Objective: To improve the understanding of pulmonaryStrongyloides stercoralis. Methods: Two paients were diagnosed with severe infection with pulmonaryStrongyloides stercoralis by respiratory ICU of Xiangya Hospital. The clinical manifestations, laboratory tests, imaging and pathological data were analyzed. Another 87 cases in the literature were reviewed from 1973 to 2013. Results: In the 2 cases, digestive symptoms were the ifrst symptom andStrongyloides stercoralis was found in the lungs. Eosinophils was detected in the 13 death cases by blood routine examination, with 10 cases≤0.05×109/L. Conclusion: The farmers were the main infected people. Patients with basic diseases or with immunosuppression due to long-term glucocorticoid treatment tend to infect and even die atfer the infection withStrongyloides stercoralis. Eosinophil granulocyte reduction shows poor prognosis, which needs early diagnosis and treatment.

Fractional exhaled nitric oxide in bronchial inflammatory lung diseases / 中南大学学报(医学版)

Objective: To explore the change of fractional exhaled nitric oxide (FeNO) and its correlation with forced expiratory volume in the ifrst second (FEV1), the ifrst second forced expiratory volume percentage of forced vital capacity (FEV1/FVC) in bronchial asthma and chronic obstructive pulmonary disease (COPD). Methods: FeNO, FEV1 and FEV1/FVC were measured in 57 suspected asthmatics (21 acute onsets, 12 non-acute and 24 non-asthma), 38 COPD patients (25 acute exacerbations and 13 stable stages) and 26 healthy subjects. Results: In the 57 suspected asthmatic patients, when the optimal cut off value of FeNO was 20.15 PPb, which was used to diagnose asthma and differentiate asthma and non-asthma, the positive predictive value, the negative predictive value, the sensitivity and the speciifcity was 94.1%, 95.7%, 97.0%, and 91.7% respectively. hTere was signiifcant difference in the FeNO level between the 33 asthmatics and 26 healthy subjects (P0.05). hTere was no signiifcant correlation between FeNO and FEV1, FEV1/FVC in patients with asthma (r=-0.186,-0.236, bothP>0.05). hTere was signiifcant difference in the levels of FeNO, FEV1 and FEV1/FVC between the 38 COPD patients and the 26 healthy subjects (all P0.05). FeNO was not correlated with FEV1 and FEV1/FVC level in COPD patients (r=-0.167,-0.285, bothP>0.05). Conclusion: FeNO level is increased obviously in patients with asthma. hTe optimal cut off value of FeNO at 20.15 PPb can differentiate asthma and non-asthma with high sensitivity and speciifcity. FeNO is higher for the acute onset than non-acute, which may be useful to evaluate the control degree. FeNO level is increased in COPD patients in the acute exacerbations, but there is no change in stable COPD patients compared with the healthy subjects.

Pathogen distribution and antibiotic resistance for hospital aquired pneumonia in respiratory medicine intensive care unit / 中南大学学报(医学版)

OBJECTIVE@#To investigate the change of pathogen distribution and antibiotic resistance of pathogens isolated from in-patients with hospital acquired pneumonia (HAP) in the Department of Respiratory Medicine Intensive Care Unit (RICU) of Xiangya Hospital in 2005 and in 2011, and to provide reasonable anti-infectious strategy.@*METHODS@#The positive susceptibility test of sputum (bronchial secretions) culture was done in patients with HAP in RICU of Xiangya Hospital in 2005 and in 2011, and the distribution feature and antibiotic resistance were compared.@*RESULTS@#1) In the two years, the main pathogen in HAP patients was Gram negative bacteria (infection rate was 68.07% and 65.21% in 2005 and in2011 respectively). The primary pathogenic bacteria were changed, and Acinetobacter baumanii became the most common Gram negative bacterium which replaced Pseudomonas aeruginosa, with infection rate 6.81% in 2005 to 40.87% in 2011. The infection rate of Pseudomonas aeruginosa reduced from 20.42% in 2005 to 15.60% in 2011. Haemophilus influenzae was rare. Staphylococcus aureus became the primary Gram positive bacteria, and its infection rate increased from 1.57% in 2005 to 4.83% in 2011, all of which were methicillin-resistant Staphylococcus aureus (MRSA). Saccharomyces albicans' positive culture rate increased significantly. 2) Compared with in 2005, the antibiotic resistance of pathogen isolated from the HAP pationts changed a lot in 2011: increased antibiotic resistance rate and decreased sensitivity to many antibiotics. Pseudomonas aeruginosa was only relatively susceptible to meropenem, cefoperazone sulbactam, ceftazidime, cefpodoxime, and andamicaxin in 2011. The resistance rate of Pseudomonas aeruginosa to levofloxacin, cyclopropane, amicacin, gentamicin, meropenem, cematrixone, and piperacilintazobactam increased obviously (P<0.05). Compared with 2005, Acinetobacter baumanii was totally susceptible to polymyxin and relatively susceptible to sulbactam, but it was almost completely resistant to Aminoglycoside antibiotics in 2011, with significant difference (P<0.01).@*CONCLUSION@#The main pathogen of HAP patients in RICU was Gram negative bacteria, with increased infection rate of Staphylococcus aureus and fungus. There is change pathogen distribution and antibiotic resistance, and the clinical initial experimental antibiotic therapy may be influenced. It is important to use antibiotics more rationally to delay the antibiotic resistance.

Endarterium injury and the related pathway in chronic intermittent hypoxia rats / 中南大学学报(医学版)

Objective:To examine the pathological change and intima thickness of thoracic aorta, detect the serum concentration of hypoxia-inducible factor-1α(HIF-1α), oxidized LDL (ox-LDL), and pentraxin 3 (PTX3) in the rat model of chronic intermittent hypoxia (CIH), and to determine the effect of CIH on endarterium injury and its possible pathway.Methods:Twenty-four male Sprague-Dawley (SD) rats were divided into 4 groups:a CIH+N-acetylcysteine (NAC) group, a CIH+normal saline (NS) group, a CIH control group and a control group. CIH rats were subjected to alternating cycles of hypoxia (6%-8%O2 in N2 for 20-25 s) and normoxia (21%O2 in N2 for 2 min) every 180 s for 7 h/d. Rats in the control group were not treated. Rats in the CIH+NAC group were treated with NAC [800 mL/(kg.d)] intraperitoneal injection, and rats in the CIH+NS group were treated with NS [5 mL/(kg.d)] intraperitoneal injection. Atfer 42 day treatment, the rats were sacriifced, blood taken, and thoracic aorta cut off. hTe serum concentration of HIF-1α, ox-LDL, and PTX3 were detected by ELISA. hTe thickness of intima was taken by computer digital image analysis. Results:Vascular endothelial cell injury and detachment were found in the thoracic aorta in the CIH and the CIH+NS group. The intima in the CIH and the CIH+NS group was thicker than that in the control and the CIH+NAC group (P<0.001). The serum concentration of HIF-1α, ox-LDL, and PTX3 in the CIH and the CIH+NS group was higher than that in the control and the CIH+NAC group (P<0.001). The serum concentration of HIF-1α, ox-LDL, and PTX3 was pairwise positive correlation, and the serum concentration of ox-LDL and PTX3 was positively correlated with the thickness of intina (P<0.001). Conclusion:hTe vascular endothelial cell injury and endarterium thickening can be induced by CIH. It is an important pathway that CIH activates oxidative stress and elevates the levels of HIF-1α, ox-LDL, and PTX3.

Large-capacity whole-lung lavage in 1 patient with pulmonary alveolar proteinosis and severe hypoxemia and literature review / 中南大学学报(医学版)

To improve the diagnosis and treatment of pulmonary alveolar proteinosis, clinical data for the first successfully treated case of pulmonary alveolar proteinosis with severe hypoxemia by large-capacity whole lung lavage in our hospital were analyzed, and relevant literatures were reviewed. A 35-year-old Han male initially presented two years ago with increasing cough and dyspnea was admitted to our hospital. Admission examination revealed severe hypoxemia, interstitial lung disease, and heavy protein deposition in the alveoli by lung biopsy. The patient received large-capacity whole-lung lavage in the operation room under general anesthesia and treatment of granulocyte-macrophage colony stimulating factor (GM-CSF). The patient's symptoms of dyspnea were alleviated markedly, and radiological findings improved and A-aDO2 decreased.

Nerve growth factor increases sodium current via interferon regulatory factor-1 pathway in rat pheochromocytoma cells / 中南大学学报(医学版)

OBJECTIVE@#To explore the effect of nerve growth factor(NGF) and interferon regulatory factor-1(IRF-1) on sodium current change of sensory neuron in rat pheochromocytoma cells.@*METHODS@#Sensory neuron rat pheochromocytoma cells were stimulated by different concentrations of NGF(0-200 ng/mL), the IRF-1 mRNA levels were examined by real-time PCR, and the activation of IRF-1 was examined by Western blot. The sodium current change was recorded by patch clamp.@*RESULTS@#Low concentration of NGF improved the sodium current, which was concentration dependent. When exposed to high concentration of NGF, the expression of IRF-1 mRNA in PC-12 was improved. Low concentration of NGF resulted in IRF-1 intronuclear transporting, and the expression was not affected. Sodium current did not occur in PC-12 cells when IRF-1 was blocked.@*CONCLUSION@#NGF can improve the sodium current in PC-12 cells concentration-dependently, and the improvement is regulated by IRF-1.

Nerve growth factor induced expression of iNOS and substance P in dorsal root ganglion sensory neuron and interferon regulatory factor-1 / 中南大学学报(医学版)

Objective To investigate the mechanism of airway neurogenic inflammation by studying the expression of inducible nitric oxide synthase (iNOS) and substance P in C7-T5 dorsal root ganglion sensory neuron cells induced by nerve growth factor (NGF) and the role of interferon regulatory factor-1 (IRF-1).Methods The dorsal root ganglia neuron (DRGn) cells were primary cultured,and then stimulated with or without NGF or NGF+interferon (IFN)-γ.Subsequently the DRGn cells were transinfected with or without green fluorescent protein (GFP)-IRF-1-vshRNA,and then stimulated with or without NGF.The expressions of iNOS and substance P were detected by real-time PCR.Results NGF induced the mRNA expression of iNOS and substance P in dorsal root ganglion sensory neuron cells,and IFN-γ increased NGF-induced iNOS mRNA expression.The expressions of iNOS and substance P in sensory neuron cells were decreased significantly at the mRNA level after IRF-1 was blocked down by IRF-1-vshRNA transinfection.Conclusion NGF is involved in the airway neurogenic inflammation by prompting the expression of iNOS and substance P through transcription factor IRF-1 in airway sensory neuron cells.IRF-1 may be a therapeutic target for airway neurogenic inflammation.

Effect of MEF2C on expression of substance P and NFL in dorsal root ganglion sensory neuron cells of rat / 中国病理生理杂志

AIM: To observe the effect of myocyte enhancer factor 2C (MEF2C) on the expression of substance P (Sub P) and neurofilament triplet L (NFL) in rat dorsal root ganglion cells (DRGn cells). METHODS: DRG neurons were dissociated and cultured, and then exposed to different concentrations of nerve growth factor (NGF, 10 μg/L, 30 μg/L, 100 μg/L or 200 μg/L) for 24 h. The neurons cultured in media with the lowest concentration of NGF (10 μg/L) served as control. Real time PCR was used for detecting the mRNA of substance P and NFL in the DRGn cells. Three MEF2C-siRNAs were transfected into PC 12 cell line by the way of chemical mediation. The best siRNA with the highest interference ratio was determined by real time PCR. The DRGn cells knocked out MEF2C gene were also transfected with siRNA, and the expressions of substance P and NFL were measured by real time PCR after stimulated with high concentration of NGF. RESULTS: The expressions of substance P and NFL increased in primary cultured rat DRG neurons in a dose-dependent manner of NGF stimulation. The expression level of MEF2C in experimental group was lower by 50% than that in control group. No change of cyclic AMP response element-binding protein (CREB) was observed. The substance P decreased by 41% in experimental group than that in control group at the same time point. The NFL was decreased by 61%. CONCLUSION: NGF may promote the synthesis of substance P and NFL in rat DRGn cells. MEF2C regulates the expression of substance P and NFL in DRGn cells in rat embryo and MEF2C may be a critical transcriptional factor involved in the airway hyperresponsiveness.

Transcription factors in spinal dorsal root ganglion in rats recurrently infected with respiratory syncytial virus / 中南大学学报(医学版)

Objective To elucidate intracellular transcription factor activation of C_7～T_5 dorsal root ganglia in rats recurrently infected with respiratory syncytial virus (RSV). Methods Eighty 1～2 weeks old Sprague-Dawley rats were randomly divided into 2 groups: a control group and a RSV-infection group. The rats in the RSV-infection group were infected with 5 ×10~5 U/mL RSV once a week and the rats in the control group were treated with culture medium without RSV. Airway response was measured after 8 weeks. Lung tissue was submitted for HE staining and in situ hybridization. The C_7～T_5 dorsal root ganglia were obtained for the preliminary screening of the intracellular transcription factors by TranSignal~(TM) protein/DNA combo array. Nuclear protein of C_7～T_5 dorsal root ganglia were extracted and submitted to Western blot. Results Airway response in the RSV-infection group was higher than that in the control group (P＜0.05). HE staining showed inflammatory cell infiltration, and in situ hybridization demonstrated positive RSV RNA in the RSV-infection rat lung which was not present in the control group, thus validating the efficacy of our model. TranSignalTM protein/DNA combo array screening showed that 55 transcription factors increased by at least 2 folds in the C_7～T_5 DRG cells of the RSV-infection group. The transcription factors Smad and interferon regulatory factor (1 or 2) were the 2 most upregulated transcription factors identified by combo array screening (59 and 43 fold increase compared with the control, respectively). Western blot confirmed Smad(1/2/3) and IRF-1 upregulate while IRF-2 remained unchanged. Conclusion Respiratory syncytial virus infection results in airway hyperresponsiveness and transcription factor activation in C7～T5 spinal adorsal root ganglia in rats, which may contribute to airway nerve network dysfunction and airway hyperresponsiveness.

The expression of ?-catenin and epidermal growth factor receptor in non-small-cell lung cancer and its clinical significance / 中国免疫学杂志

Objective: To investigate the expression of ?-catenin and epidermal growth factor receptor in non-small-cell lung cancer and its clinical significance. Methods: The expression of ?-catenin and epidermal growth factor receptor in 58 cases of non-small-cell lung cancer tissue sections were detected by immunohistochemistry. Correlations were investigated between fj-catenin and EGFR immunostaining in primary tumors and histological grade, lymph node stage.Results:23 of 58 cases showed strong ?-catenin immunostaining and 27 of 58 cases showed strong EGFR immunostaining. ?-catenin expression showed significant correlation with grades of differentiation. There were significant correlations between ?-catenm and ECFR. expression and lymph node metastasis. Conclusion: The change of ?-catenin and ECFR expression in surgically treated NSCLC are clearly associated with lymph node metastasis and histological grade.