Association between vitamin D level and blood eosinophil count in healthy population and patients with chronic obstructive pulmonary disease / 南方医科大学学报

OBJECTIVE@#To investigate the prevalence of vitamin D deficiency and its association with blood eosinophil count in healthy population and patients with chronic obstructive pulmonary disease (COPD).@*METHODS@#We analyzed the data of a total 6163 healthy individuals undergoing routine physical examination in our hospital between October, 2017 and December, 2021, who were divided according to their serum 25(OH)D level into severe vitamin D deficiency group (< 10 ng/mL), deficiency group (< 20 ng/mL), insufficient group (< 30 ng/mL) and normal group (≥30 ng/mL). We also retrospectively collected the data of 67 COPD patients admitted in our department from April and June, 2021, with 67 healthy individuals undergoing physical examination in the same period as the control group. Routine blood test results, body mass index (BMI) and other parameters were obtained from all the subjects, and logistic regression models were used to investigate the association between 25(OH)D levels and eosinophil count.@*RESULTS@#The overall abnormal rate of 25(OH)D level (< 30 ng/mL) in the healthy individuals was 85.31%, and the rate was significantly higher in women (89.29%) than in men. Serum 25(OH)D levels in June, July, and August were significantly higher than those in December, January, and February. In the healthy individuals, blood eosinophil counts were the lowest in severe 25(OH)D deficiency group, followed by the deficiency group and insufficient group, and were the highest in the normal group (P < 0.05). Multivariable regression analysis showed that an older age, a higher BMI, and elevated vitamin D levels were all risk factors for elevated blood eosinophils in the healthy individuals. The patients with COPD had lower serum 25(OH)D levels than the healthy individuals (19.66±7.87 vs 26.39±9.28 ng/mL) and a significantly higher abnormal rate of serum 25(OH)D (91% vs 71%; P < 0.05). A reduced serum 25(OH)D level was a risk factor for COPD. Blood eosinophils, sex and BMI were not significantly correlated with serum 25(OH)D level in patients with COPD.@*CONCLUSION@#Vitamin D deficiency is common in both healthy individuals and COPD patients, and the correlations of vitamin D level with sex, BMI and blood eosinophils differ obviously between healthy individuals and COPD patients.

Delayed diagnosis is associated with greater disease severity of chronic obstructive pulmonary disease / 南方医科大学学报

OBJECTIVE@#To investigate the association of the time of initial diagnosis with the severity of chronic obstructive pulmonary disease (COPD).@*METHODS@#A total of 803 patients who were diagnosed to have COPD for the first time in our hospital between May 2015 to February 2018 were enrolled in this study.The diagnoses of COPD and asthma COPD overlap (ACO) were made according GOLD guidelines and european consensus definition.Lung function of the patients was graded according to the GOLD guidelines.@*RESULTS@#The patients with COPD had a mean age of 61.8±9.9 years,including 726 male and 77 female patients.The course of the patients (defined as the time from symptom onset to the establishment of a diagnosis) was 3(0.5,8) years.Among these patients,85.2% had a moderate disease severity (FEV1%<80%),and 48.3% had severe or very severe conditions (FEV1%<50%);47.0% of them were positive for bronchial dilation test.In the overall patients,295(36.7%) were also diagnosed to have ACO,and the mean disease course of ACO[3(1,9) years]was similar to that of COPD[3(0.5,8) years](>0.05).A significant correlation was found between the disease course and the lung function of the patients.Multiple linear regression analysis showed that an older age and a longer disease course were associated with poorer lung functions and a greater disease severity.@*CONCLUSIONS@#The delay of the initial diagnosis is significantly related to the severity of COPD.

Analysis of integrated healthcare model for Chronic Obstructive Pulmonary Disease patients / 中国卫生政策研究

Objective: The aim of this paper is to identify the basic organizational structure and the key elements of integrated healthcare model of patients with Chronic Obstructive Pulmonary Disease (COPD) and propose an appropriate development strategy.Methods: Based on the literature review of research articles about integrated care on patients with COPD, an analysis was conducted with the help of the Chronic Care Model (CCM) which is a chronic disease management model.Results: From of a total 16 articles about 13 case studies were found.An integrated healthcare of COPD was carried out in 10 hospital-based or community-based care programs.Most of the patients were the elderly and health status were moderately severe or more severe.The components of healthcare programs varied from 4 to 12 included at least two CCM dimension.A coordinator or a case manager was appointed in all healthcare programs and a follow-up plan was made as well.Decision making was supported by clinic guideline and specialist resource in 9 integrated healthcare programs which community facilities involved.All programs included self-management with health education and individualized behavioral support was in 10 programs.The action plan was applied in 8 studies.8 studies using a clinical information system connected health care provider and patients.Conclusions: COPD integrated care program can be constructed according to the management model of chronic disease, and it is suggested that we can organize the COPD integrated care program based on CCM and the program comprises 4 organizational components of at least two CCM dimensions.The key elements of COPD integrated healthcare are to appoint a coordinator, to make a follow-up plan, and the necessity of community participation to support decision making, support self-management by education and individualized behavioral management with an action plan.

Effect of MKK34 on airway β-catenin in a HDM-induced mouse asthma / 实用医学杂志

Objective To explore the role of MKK34 (a peptide spanning a C-terminal α-helical region in TSLP) on airway inflammation and β-catenin of airway epithelium in a HDM-induced mouse asthma.Methods 32 male BALB/c mice were randomly divided into control,MKK34,asthma and MKK34 + HDM groups.The mice in the asthma group were exposed to HDM for five consecutive days and the MKK34 + HDM group was pretreated with MKK34 1 h prior to the HDM intranasally treated.After 8 weeks' treatment,animal lung function test and pathological staining were performed to evaluate the asthma situation,IL-4,IFN-γin bronchoalveolar lavage fluid and IgE in the serum were detected,immunohistochemistry and western blot were used to assess β-catenin and p-ERK,t-ERK levels.Results Airway reactivity,IL-4 and IgE in the asthma group were significantly higher than that in the control group.Treatment with MKK34 significantly decreased airway hyperresponsiveness,IL-4 and IgE.HE staining demonstrated the chronic bronchitic inflammation in the lungs of asthma group.β-catenin in the control group was distributed evenly at the cytomembrane of epithelial cells.In the asthma group,β-catenin was disordered in epithelial cells and its expression was decreased.Treatment with MKK34 ameliorated the damage of β-catenin and chronic bronchitic inflammation.The protein levels of p-ERK1/2 increased obviously in the asthma group.The pretreated group significantly decreased the expression of p-ERK1/2.Conclusions MKK34 can ameliorate the airway inflammation and the destruction of β-catenin of airway epithelium in a HDM-induced mouse asthma.The ERK pathway may play a role in this process.

1,25(OH)2D3 protects against BLM-induced pulmonary fibrosis by inhibiting activation of STAT3 / 实用医学杂志

Objective To investigate the impact of 1,25(OH)2D3 on histological changes and activation of STAT3 in BLM?induced pulmonary fibrosis mice. Methods 30 male C57BL/6 mice were randomly divided into control group ,BLM group and BLM+VD group. Mice in BLM group and BLM+VD group received intratracheal injection of BLM(3 U/kg). Control group were intratracheally injected equal volume of sterile saline. From the first day after the surgery,mice in BLM+VD group received intraperitoneal injection of VD (5μg/kg·d). After 21 days, H&E and Masson′s trichrome staining were carried out. Aschroft score were used to evaluate histological changes in lungs. IL?6,IL?4 and INF?γin BALF were assessed by Elisa. p?STAT3,α?SMA and Collagen I were detected by western blot (WB) and immunohistochemistry. Results Fibrosis score and level of α?SMA,Collagen I in BLM group were significantly higher than that in control group (P < 0.05). However ,treatment with VD effectively at?tenuated fibrosis (P<0.05). IL?6 and IL?4 increased while INF?γwas decreased in BALF of BLM group (P<0.05). VD could ameliorate these changes. Upregulation and neuclear translocation of p?STAT3 were observed in BLM group,while VD intervention could inhibit phosphorylation of STAT3. Conclusions VD attenuate BLM?induced pulmonary fibrosis and regulate inflammatory cytokines probably by blocking STAT3 activation.

1,25-dihydroxyvitamin D3 pretreatment inhibits house dust mite-induced thymic stromal lymphopoietin release by human airway epithelial cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of 1,25-dihydroxyvitamin D3 (1,25VD3) on house dust mites (HDM)-induced expression of thymic stromal lymphopoietin (TSLP) in human airway epithelial cells in vitro.</p><p><b>METHODS</b>Human airway epithelial 16HBE cells were incubated with 200, 400, and 800 U/L in the absence or presence of 1,25VD3 (10(-8) mol/L) for 6 h and 24 h, and TSLP mRNA and protein expressions in the cells were assessed using quantitative PCR and ELISA.</p><p><b>RESULTS</b>16HBE cells incubated with HDM at 200, 400, and 800 U/L showed significantly increased TSLP mRNA and protein expressions (P<0.05). Pretreatment of the cells with 1,25VD3 obviously lowered 400 U/L HDM-induced TSLP expressions (P<0.05), but 1,25VD3 added along with HDM in the cells did not produce significant effects on TSLP expressions (P=0.58).</p><p><b>CONCLUSION</b>Both 1,25VD3 and HDM can induce TSLP expression and release in 16HBE cells, but pretreatment with 1,25VD3 can decrease HDM-augmented TSLP expression in the cells.</p>

Effect of thymic stromal lymphopoietin on human bronchial epithelial permeability / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of thymic stromal lymphopoietin (TSLP) on the permeablily of monolayer bronchial epithelial cells in vitro.</p><p><b>METHODS</b>Cultured human bronchial epithelial cell line 16HBE was exposed to 0.1 or 1 ng/ml TSLP for 0, 0.5, 6, 12, or 24 h, and the epithelial monolayer permeability was assessed by measuring transepithelial electrical resistance (TER), permeability to FITC-labeled dextran (FITC-DX) and expression of E-cadherin.</p><p><b>RESULTS</b>Compared with the control cells group, 16HBE cell monolayer showed significantly increased TER (P<0.001) and decreased FITC-DX fluorescence in the lower chamber (P<0.05) following exposure to 0.1 and 1 ng/ml TSLP, but these changes were not dose-dependent. Exposure to 0.1 ng/ml TSLP resulted in significantly increased expression of E-cadherin. The 16HBE monolayer exposed to 0.1 ng/ml TSLP for 24 h showed the most obvious increase of TER and E-cadherin expression (P<0.05); FITC-DX fluorescence level was markedly decreased after TSLP exposure for 12 h and 24 h (P<0.05), and the effect was more obvious in 12 h group.</p><p><b>CONCLUSION</b>TSLP can protect the barrier function of normal bronchial epithelial cells in vitro.</p>

Effect of ethyl pyruvate on E-cadherin of airway epithelium in a TDI-induced mouse asthma / 实用医学杂志

Objective To explore the role of ethyl pyruvate (EP) on E-cadherin of airway epithelium and airway inflammation in a TDI-induced mouse asthma model. Methods 30 male BALB/c mice were randomly divided into control group , asthma group and EP group. On day 1 and 8 , mice in asthma group and EP group were treated with 0.3%TDI on the dorsum of both ears for sensitization. And on day 15 , 18 and 21 the mice underwent an aerosol inhalation of 3% TDI, and saline (100 mg/kg) was injected intraperitoneally 1 hour before inhalation. The control group underwent acetone and olive oil (AOO) sensitization on day 1 and 8, AOO challenge on day 15, 18 and 21. Saline (100 mg/kg) was injected intraperitoneally 1 hour before challenge. One hour before each challenge, mice were given EP (100mg/kg) or vehicle via intraperitoneal injection. On day 22, airway reactivity, IL-4 , IFN-γand IgE in the serum were detected , immunohistochemistry and WB were used to assess E-cadherin levels. Results Airway reactivity, IL-4, IFN-γin and IgE in the serum in asthma group are significantly higher than that in control group (P<0.05). Treatment with EP dramatically decreased airway hyperresponsiveness in TDI-challenged mice, as well as IL-4, IFN-γ and IgE (P < 0.05). E-cadherin in control group was distributed evenly at the connection of epithelial cells. E-cadherinin distribution was chaotic and its expression was decreased in asthma group. EP intervention can ameliorate the damage of E-cadherinin. Conclusions EP can ameliorate the destruction of E-cadherin in airway epithilum by TDI.

Significance of dynamic monitoring PCT in patients with bacterial hospital acquired pneumonia / 实用医学杂志

Objective To demonstrate the influence of PCT concentration and its descent to the prognosis of patients with hospital acquired bacterial pneumonia. Methods The PCT concentration was determined. One hundred and thirteen HAP patients were enrolled from September 2011 and November 2012 , including 64 patients in the non-survival group and 49 patients in the survival group , and 92 non-infected patients in the control group. The relationship between PCT and hospital days and survival rate was analyzed. Results The initial value of PCT in the non-survival group and in the survival group were higher than that in the control group, while the PCT in the non-survival group was the highest, with significant difference (P =0.0002). Taking PCT = 0.78 μg/L as the cut-off value, the sensitivity and specificity to predict the mortality of the HAP patients was 0.66 and 70%, respectively. A significant negative correlation was shown between PCT value and hospital days in the non-survival group. The survival rate of patients with PCT decrease over 50% was higher than that of patients with PCT decrease less than 50% after treatment. Conclusion Dynamic monitoring PCT in patients with bacterial HAP possesses a certain significance.

Establishment and Evaluation of a Simplified Evaluation System of Acute Respiratory Distress Syndrome

PURPOSE: In recent years, a variety of acute respiratory distress syndrome (ARDS) evaluation systems have been developed worldwide; however, they are not so convenient for the doctors clinically, we decided to establish and evaluate a simplified evaluation system of ARDS (SESARDS). MATERIALS AND METHODS: Data from 140 ARDS patients (derivation data set) were collected to screen for prognostic factors affecting outcomes in ARDS patients. By logistic regression analysis, scores were allocated to corresponding intervals of the variables, respectively, by means of analysis of the frequency distribution to establish a preliminary scoring system. Based on this primary scoring system, a definitive evaluation scheme was created through consultation with a panel of experts. The scores for the validation data set (92 cases) were assigned and calculated by their predictive mortality with the SESARDS and acute physiology and chronic health evaluation II (APACHE II). The performance of SESARDS was compared with that of APACHE II by means of statistical analysis. RESULTS: The factors of age, pH, Glasgow coma scale (GCS), oxygenation index (OI), and the lobes of lung were associated with prognosis of ARDS respectively. The sensitivity and specificity of SESARDS for the validation data set were 96.43% and 58.33%, respectively. On the AUC, no significant difference between APACHE II and SESARDS was detected. There were no significant differences between the prediction and the actuality obtained by SESARDS for the validation data set the SESARDS scores were positively correlated with the actual mortality. CONCLUSION: SESARDS was shown to be simple, accurate and effective in predicting ARDS progression.

Hydrogen peroxide induces high mobility group box 1 release in human bronchial epithelial cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of hydrogen dioxide (H(2)O(2)) on the release and translocation of high mobility group box 1 release (HMGB1) from normal human bronchiolar epithelial cells (HBE).</p><p><b>METHODS</b>MTT assay was used to assess the viability of HBE135-E6E7 cells exposed to different concentrations of H(2)O(2). The expression and location of HMGB1 in the cytoplasm, nuclei and culture medium of the exposed cells were determined using Western blotting and immunofluorescence assay.</p><p><b>RESULTS</b>Exposure to 125 µmmol/L H(2)O(2) did not obviously affect the cell viability. At the concentration of 250 µmmol/L, H(2)O(2) significantly decreased the cell viability (P<0.05), but significant cell death occurred only after exposure to 400 µmmol/L H(2)O(2) (P=0.000). Compared with the control cells, the cells exposed to 12.5, 125 and 250 µmmol/L H(2)O(2) for 24 h showed significantly increased levels of HMGB1 in the culture medium (P<0.05), and exposure to 125 µmmol/L H(2)O(2) for 12 and 24 h also caused significantly increased HMGB1 level (P<0.05). Exposure to 125 µmmol/L H(2)O(2) for 24 h significantly increased HMGB1 expression in the cytoplasm but decreased its expression in the nucleus. HMGB1 translocation from the nuclei to the cytoplasm and to the plasmalemma occurred after 125 µmmol/L H(2)O(2) exposure for 12 h and 24 h, respectively.</p><p><b>CONCLUSION</b>H(2)O(2) can induce HMGB1 translocation and release in human bronchial epithelial cells, suggesting the involvement of HMGB1 in airway oxidative stress in chronic inflammatory diseases such as asthma and COPD.</p>

High-mobility group box protein 1 in synergy with interleukin-1β promotes interleukin-8 expression in human airway epithelial cells in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To test the effect of high-mobility group box protein 1 (HMGB1) alone or in synergy with interleukin-1β (IL-1β) on the expression of IL-8 in human airway epithelial cells in vitro.</p><p><b>METHODS</b>Human airway epithelial 16HBE and A549 cell lines were incubated with HMGB1 (100 ng/ml) in the absence or presence of IL-1β (10 ng/ml) for 24 h, and the changes of IL-8 mRNA and protein expressions were assessed using quantitative PCR and enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>In the two human airway epithelial cell lines, HMGB1 alone did not produce obvious effect on the expression of IL-8, but in the presence of IL-1β, HMGB1 caused a significant increase of IL-8 expressions at both the mRNA and protein levels.</p><p><b>CONCLUSION</b>HMGB1 in synergy with IL-1β increases the expression of IL-8 in human airway epithelial cells, which provides new evidence that HMGB1 contributes to neutrophilic airway inflammation by regulating IL-8 expression.</p>

Effect of 25-hydroxyvitamin D(3) on vitamin D receptor expression and distribution in human bronchial epithelial cells in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the effect of 25-hydroxyvitamin D(3) on the expression and distribution of vitamin D receptor in normal human bronchial epithelial cells.</p><p><b>METHODS</b>MTT assay was used to assess the viability of human airway epithelial cell line 16HBE following a 24-h exposure to different concentrations of 25-hydroxyvitamin D(3). Real-time quantitative PCR, Western blotting, and immunofluorescence assay were used to observe the expression and distribution of vitamin D receptor in the cells following the exposure.</p><p><b>RESULTS</b>Compared with the control cells, 16HBE cells exposed to different concentrations of 25-hydroxyvitamin D(3) exhibited no significantly increase in the expression or distribution of vitamin D receptor.</p><p><b>CONCLUSION</b>The influence of 25-hydroxyvitamin D(3) on bronchial epithelial cells might be independent of the expression and translocation of vitamin D receptor.</p>

Identification of differentially expressed genes associated with cell adhesion and immune regulation in peripheral blood eosinophils from asthmatic patients with suppression subtractive hybridization / 中国病理生理杂志

AIM: To determine differentially expressed genes associated with cell adhesion and immune regulation in peripheral blood eosinophils from asthmatic patients. METHODS: Peripheral blood eosinophils were isolated from the asthmatic patients at the time of exacerbation and after improvement. Total RNA was extracted. Super SMART PCR cDNA was synthesized, suppression subtractive hybridization (SSH) and PCR-select differential screening technology were used to detect expressed genes. The differentially expressed genes were sequenced. RESULTS: High efficiency subtractive cDNA library was constructed successfully. Differential screening identified 15 differentially expressed genes, which were Charcot-Leyden crystal protein (CLC protein; galectin-10), putative pre-mRNA splicing regulator female-lethal (2D), aquaporin 9 (AQP9), IL-8, slingshot 2L (SSH-2L), PP1 catalytic subunit, beta isoform, helicase with zinc finger domain (HELZ), ?2-microglobin (?2-MG) and a gene associated with mitochondrion. CONCLUSION: Increased expression of these genes might be associated with eosinophil migration, adhesion and immune regulation. Intervention of these pathways may provide a theoretical base for future new targeting treatment for asthma.

Expression of VDUP1 in peripheral eosinophil of asthmatic patients and its relation with eosinophil activation / 中国病理生理杂志

AIM: To investigate the expression of vitamin D3 up-regulated protein 1 (VDUP1) in peripheral eosinophils of asthma patients and its relation with eosinophil activation.METHODS: 10 normal volunteers and 31 mild to moderate asthma patients were selected. Symptom severity, pulmonary function index, induced sputum eosinophil counts were recorded. Then, gene and protein expressions of VDUP1 and ?-actin were evaluated by RT-PCR and Western blotting, respectively. In addition, eosinophils were incubated with IL-5, both VDUP1 and ?-actin were amplified by RT-PCR. The eosinophil cationic protein (ECP) of supernatant and serum were also detected by ELISA assay. RESULTS: There was a significant decrease in expression of VDUP1 in asthma attack patients without treatment compared with normal volunteers and patients in remission. In contrast, no significant difference between the patients in remission and normal volunteers was observed. In patients with asthma attacks, a negative relationship between expression intensity of VDUP1 and EOS% in induced sputum and serum ECP concentration was also observed. The expression of VDUP1 in eosinophils was decreased by IL-5 stimulation, simultaneously, the ECP in supernatant was increased. CONCLUSION: The expression of VDUP1 in eosinophils decreases in asthma patients, and is negatively associated with serum ECP and induced sputum EOS%. EOS activation by IL-5 may be related to VDUP1 pathway.