Early risk factors of the exacerbation of coronavirus disease 2019 pneumonia.

The purpose of this study was to investigate the early risk factors for the exacerbation of coronavirus disease 2019 (COVID-19) pneumonia. Restrospective analysis of clinical data of 85 patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including gender, age, comorbidities, symptoms, blood routine, clotting profile, biochemical examination, albumin, myocardial enzyme profile, inflammatory markers, and chest computed tomography (CT). All laboratory examinations were measured within first 24 hours after admission, and chest CT was performed before admission. A total of 56 (65.9%) patients had a history of exposure to the Huanan seafood market in Wuhan. Fever and dry cough accounted for the highest percentage of all symptoms. Male COVID-2019 patients were more likely to develop severe pneumonia. Patients with severe and critical conditions are older and have higher rates of hypertension (P = .003) and coronary heart disease (P = .017). All severe and critical patients infected with SARS-CoV-2 showed bilateral lung involvement and have more multiple lobes involvement than common patients (P < .001). Severe and critical patients showed higher white blood cell count (P = .006), neutrophil (NEU) count (P = .001), NEU% (P = .002), procalcitonin (P = .011), C-reactive protein (P = .003), prothrombin time (P = .035), D-dimer (P = .025), aspartate aminotransferase (P = .006), and lower lymphocyte (LYM) count (P = .019), LYM% (P = .001), albumin (P < .001). Logistic regression analysis showed that NEU count is an independent risk factor for deterioration, with the threshold of 6.5 × 109 ·L-1 . We concluded that the laboratory independent risk factor for the progression of COVID-19 pneumonia is NEU count. In addition, COVID-19 patients with bilateral lung involvement or multiple lobes involvement should be taken seriously and actively treated to prevent deterioration of the disease.

ADRB2 signaling promotes HCC progression and sorafenib resistance by inhibiting autophagic degradation of HIF1α.

BACKGROUND & AIMS: Considerable evidence suggests that adrenergic signaling played an essential role in tumor progression. However, its role in hepatocellular carcinoma (HCC) and the underlying mechanisms remain unknown. METHODS: The effect of adrenaline in hepatocarcinogenesis was observed in a classical diethylnitrosamine-induced HCC mouse model. Effects of ADRB2 signaling inhibition in HCC cell lines were analyzed in proliferation, apoptosis, colony formation assays. Autophagy regulation by ADRB2 was assessed in immunoblotting, immunofluorescence and immunoprecipitation assays. In vivo tumorigenic properties and anticancer effects of sorafenib were examined in nude mice. Expression levels of ADRB2 and hypoxia-inducible factor-1α (HIF1α) in 150 human HCC samples were evaluated by immunohistochemistry. RESULTS: We uncovered that adrenaline promoted DEN-induced hepatocarcinogenesis, which was reversed by the ADRB2 antagonist ICI118,551. ADRB2 signaling also played an essential role in sustaining HCC cell proliferation and survival. Notably, ADRB2 signaling negatively regulated autophagy by disrupting Beclin1/VPS34/Atg14 complex in an Akt-dependent manner, leading to HIF1α stabilization, reprogramming of HCC cells glucose metabolism, and the acquisition of resistance to sorafenib. Conversely, inhibition of ADRB2 signaling by ICI118,551, or knockdown ADRB2 expression, led to enhanced autophagy, HIF1α destabilization, tumor growth suppression, and improved anti-tumor activity of sorafenib. Consistently, ADRB2 expression correlated positively with HIF1α in HCC specimens and was associated with HCC outcomes. CONCLUSIONS: Our results uncover an important role of ADRB2 signaling in regulating HCC progression. Given the efficacy of ADRB2 modulation on HCC inhibition and sorafenib resistance, adrenoceptor antagonist appears to be a putative novel treatment for HCC and chemoresistance. LAY SUMMARY: ADRB2 signaling played an essential role in sustaining hepatocellular carcinoma cell proliferation and survival. ADRB2 signaling negatively regulated autophagy, leading to hypoxia-inducible factor-1α stabilization, reprogramming of hepatocellular carcinoma cells glucose metabolism, and the acquisition of resistance to sorafenib. Adrenoceptor antagonist appears to be a putative novel treatment for hepatocellular carcinoma and chemoresistance.

A phase 4 multicentre, 2×2 factorial randomised, double-blind, placebo-controlled trial to investigate the efficacy and safety of tobramycin inhalation solution for Pseudomonas aeruginosa eradication in bronchiectasis: ERASE.

Chronic Pseudomonas aeruginosa (PA) infection significantly contributes to morbidity and mortality in bronchiectasis patients. Initiating antibiotics early may lead to the eradication of PA. Here we outline the design of a trial (ERASE; NCT06093191) assessing the efficacy and safety of inhaled tobramycin, alone or with oral ciprofloxacin, in bronchiectasis patients with a new isolation of PA. This multicentre, 2×2 factorial randomised, double-blind, placebo-controlled, parallel-group trial includes a 2-week screening period, a 12-week treatment phase (with a combination of ciprofloxacin or a placebo at initial 2 weeks) and a 24-week follow-up. 364 adults with bronchiectasis and a new PA isolation will be randomly assigned to one of four groups: placebo (inhaled saline and ciprofloxacin placebo twice daily), ciprofloxacin alone (750 mg ciprofloxacin and inhaled saline twice daily), inhaled tobramycin alone (inhaled 300 mg tobramycin and ciprofloxacin placebo twice daily) or a combination of both drugs (inhaled 300 mg tobramycin and 750 mg ciprofloxacin twice daily). The primary objective of this study is to assess the proportion of patients successfully eradicating PA in each group by the end of the study. Efficacy will be evaluated based on the eradication rate of PA at other time points (12, 24 and 36 weeks), the occurrence of exacerbations and hospitalisations, time to first pulmonary exacerbations, patient-reported outcomes, symptom measures, pulmonary function tests and the cost of hospitalisations. To date no randomised trial has evaluated the benefit of different PA eradication strategies in bronchiectasis patients. The ERASE trial will therefore generate crucial data to inform future clinical guidelines.

[The prevalence and risk factors of bronchiectasis in residents aged 40 years old and above in seven cities in China].

OBJECTIVE: To investigate the prevalence and risk factors of bronchiectasis in urban city of China. METHODS: A cross-sectional survey was conducted in 17 urban areas in Beijing, Shanghai, Tianjin, Chongqing cities, and Guangdong, Liaoning, Shanxi provinces. In this study, urban population-based cluster samples were randomly selected from each city/province. In the selected city communities, all residents at least 40 years old were recruited, interviewed with questionnaires and tested with spirometry. Each participant was asked whether he/she was ever diagnosed as bronchiectasis by physician, whether had symptoms of respiratory diseases and possible risk factors, etc. RESULT: Data of 10 811 participants was enrolled for analysis, with a response rate of 75.4% (10 811/14 337). The overall prevalence of physician-diagnosed bronchiectasis was 1.2% (135/10 811), with 1.5% (65/4382) in male and 1.1% (70/6429) in female, without statistical difference in gender (χ² = 3.289, P = 0.070). Prevalence of bronchiectasis increased with age (χ² = 31.029, P < 0.001). There were no statistical significances in crude prevalences of bronchiectasis among cities (χ² = 10.572, P = 0.103), while there was a significant difference among cities after adjustment with confounders (Wald value = 22.116, P = 0.001), by using logistic regression analysis. Logistic regression analysis showed, bronchiectasis was significantly associated with elder ( ≥ 70 years vs 40-49 years; OR = 4.11, 95% CI 2.29-7.36), the family history of respiratory diseases (having two subjects with respiratory diseases in family vs no suffered relatives; OR = 2.04, 95% CI 1.06-3.94), respiratory infection during childhood (suffering two kinds of respiratory diseases vs never; OR = 4.89, 95% CI 2.03-11.81), exposure to coal (OR = 2.30, 95% CI 1.17-4.52), chronic pharyngitis (OR = 3.96, 95% CI 1.38-11.40) and pulmonary tuberculosis (OR = 3.07, 95% CI 1.89-4.98), heart diseases (OR = 1.64, 95% CI 1.11-2.42) and lung cancer(OR = 18.61, 95% CI 7.67-45.18). CONCLUSION: The prevalence of bronchiectasis in population aged 40 years old and above in urban area in China is high and associated with multiple factors such as age, family history of respiratory diseases, respiratory infection during childhood, exposure to coal, chronic pharyngitis, pulmonary tuberculosis, heart diseases, lung cancer and so on.

[Respiratory physicians' knowledge, attitude and practice of tobacco control and their smoking status in the city of Chongqing].

OBJECTIVE: To investigate the smoking status, knowledge of smoking hazards, attitude of tobacco control and skill of assisting smoking cessation in respiratory physicians in the city of Chongqing and therefore to provide references for their further participation in social tobacco control. METHODS: With a self-designed questionnaire, a cross-sectional study was conducted on respiratory physicians of 8 hospitals in Chongqing, which were selected with stratified random sampling method. All the data were inputted with software Epidata 3.1 and were analyzed with SPSS 13.0. RESULTS: A total of 428 valid questionnaires were retrieved, with a valid rate of 95.1% (428/450). The total smoking rate was 12.4% (95%CI: 9.3% - 15.5%), with 7.4% in physicians of teaching hospitals, 8.13% in those of hospitals located in urban areas, and 19.0% in those of hospitals located in suburban district counties. The differences in smoking rates in the respiratory physicians among different hospitals showed statistical significance (χ(2) = 11.734, P = 0.014). The smoking rate of the male was higher than that of the female. Of the surveyed doctors, 80.14% had awareness that tobacco dependence was a neuropsychiatric disease characterized as nicotine addiction, while 34.8% claimed that they had no idea about quitting smoking drugs. Although all participants claimed that they knew the harm of secondhand smoke, 16.36% of them still had never come forward to prevent smoking behavior in hospitals. There was only 27.4% of the surveyed discouraging smoking behavior with the reason of unwillingness to breath in secondhand smoke, while 53.9% of the surveyed discouraged smoking behavior because of regulations of hospitals. Most of the surveyed did relatively well in routinely inquiring and recording the smoking status of patients, but only 27.1% of them had recommended specific quitting smoking methods to patients, and there were few successful cases in practice. The situations of smoking cessation assistance in hospitals located in urban areas and suburban district counties were better than that in teaching hospitals. CONCLUSIONS: The smoking rate of the respiratory physicians (especially male doctors) in Chongqing is high. There is lack of enthusiasm in preventing smoking behavior in public area of hospitals. The knowledge and skills of smoking cessation are lacking as well. Therefore more training programs for smoking control are needed. Respiratory physicians in primary hospitals or community health centers can play a more important role in smoking control.

The identification of miR-375 as a potential biomarker in distal gastric adenocarcinoma.

MicroRNAs (miRNAs) are endogenous small noncoding RNAs that negatively regulate gene expression at the posttranscriptional level and play an important role in carcinogenesis. Herein, we characterized the global expression of miRNA in distal gastric adenocarcinomas and determined if circulating miRNAs could be used as biomarkers for distal gastric adenocarcinoma. We used a microarray screening system to detect dysregulated miRNAs in distal gastric adenocarcinoma tissues. The expression of a subset of five aberrantly expressed miRNAs (miR-375, -196b, -204, -18b, and -93) were further quantified in an independent set of clinical samples of distal gastric adenocarcinoma by real-time quantitative RT-PCR (rt-qRT-PCR). We also used rt-qRT-PCR to investigate the expression levels of putative miRNA biomarkers in serum and tumor cell lines. In our study, the expression of a subset of microRNAs was altered in distal gastric adenocarcinoma compared to normal tissue, miR-375 was significantly downregulated in distal gastric adenocarcinoma tissues, to a level that was significantly lower than cardia adenocarcinoma (p < 0.05). The circulating serum levels of miR-375 in patients who had distal gastric adenocarcinoma were also much lower than normal controls (p < 0.001). As a biomarker, miR-375 yielded a receiver operating characteristic area under the curve of 0.835. The specificity and sensitivity was 80% and 85%, respectively, in the discrimination of distal gastric adenocarcinoma from control, at a normalized cutoff of 0.218. The expression of miR-375 was downregulated both in distal gastric adenocarcinoma tissues and serum of patients with distal gastric adenocarcinoma. These data suggest miR-375 is a potential biomarker for distal gastric adenocarcinoma.

Th17 cells are increased with severity of liver inflammation in patients with chronic hepatitis C.

BACKGROUND AND AIM: As a newly identified subset of T helper cells, T-helper 17 cells (Th17) are major mediators of inflammation-associated disease. Some reports have revealed significantly increased Th17 cells in hepatitis B virus-infected patients, and a recent study has demonstrated that hepatitis C virus (HCV)-specific Th17 cells can be induced in vitro and regulated by transforming growth factor-ß. This study attempted to characterize the role of Th17 cells in the disease progression of chronic hepatitis C (CHC). METHODS: The current study enrolled 53 patients with CHC and 23 healthy controls, in which the circulating and liver-infiltrating Th17 cells were monitored. RESULTS: We found that CHC patients had increased proportions of both circulating and liver-infiltrating Th17 cells compared to healthy individuals, and both measures of Th17 cells were correlated with severity of liver inflammation. We further demonstrated that the HCV-specific Th17 cells were correlated with liver damage but not HCV viral replication. CONCLUSIONS: Such a correlation between the severity of liver damage of CHC and Th17 cells illustrated in this study sheds some light on the understanding of the pathogenesis of CHC.

Relationship between the anti-inflammatory properties of salmeterol/fluticasone and the expression of CD4⁺CD25⁺Foxp3⁺ regulatory T cells in COPD.

BACKGROUND: Salmeterol and fluticasone combination (SFC) has anti-inflammatory effects and improves clinical symptoms in patients with chronic obstructive pulmonary disease (COPD). However, the anti-inflammatory mechanism of SFC remains unclear. In this study, we investigated the inflammatory responses of COPD, as well as the relationship of the inflammatory factors with the levels of CD4+CD25+Foxp3+ regulatory T cells (Foxp3+Tregs) after SFC therapy. METHODS: Twenty-one patients with moderate or severe COPD received treatment with 50/500 µg of SFC twice a day for 12 weeks. Before and after treatment, the patients were evaluated using the Modified Medical Research Council (MMRC) dyspnea scale and by conducting a 6-min walk test. The number of neutrophils, monocytes and lymphocytes in induced sputum were counted. Levels of cytokines, including pre-inflammatory IL-8, TNF-α, IL-17A and cytokine IL-10, in the sputum supernatant and peripheral blood were measured by ELISA. The proportion of Foxp3+Tregs in the total CD4+ T cell of the peripheral blood was determined by flow cytometry. The relationship between IL-17A levels and the percentage of Foxp3+Tregs was analyzed by statistical analysis. RESULTS: After treatment with SFC, the forced expiratory volume in 1 s as a percentage of predicted values (FEV1%) and the 6-min walk distance in the COPD patients significantly increased, while dyspnea scores decreased. The total number of cells, neutrophils, and the percentage of neutrophils in induced sputum reduced notably, while the proportion of monocytes was significantly increased. Levels of the inflammatory cytokines IL-8, TNF-α, and IL-17A in the sputum supernatant and in the blood were markedly lowered, while IL-10 levels were unchanged. The proportion of Foxp3+Tregs in the total CD4+T cell population in the peripheral blood was drastically higher than that before treatment. The level of IL-17A was negatively correlated with the proportion of Foxp3+Tregs in CD4+T cells. CONCLUSION: SFC can reduce the levels of inflammatory factors and improve symptoms of COPD. The levels of inflammatory factors are associated with the variation of Foxp3+Tregs in COPD. TRIAL REGISTRATION: This study was registered with http://www.chictr.org (Chinese Clinical Trial Register) as follows: ChiCTR-TNC-10001270.

[The clinical characteristics of ulcerative colitis of 525 hospital-based patients from 1994 to 2009].

OBJECTIVE: To investigate the clinical characteristics and chronological change of ulcerative colitis (UC) in the Chinese PLA General Hospital in near 16 years. METHODS: Patients diagnosed with UC during the period from 1994 to 2009 in the Chinese PLA General Hospital were registered and their clinical profiles were analyzed. RESULTS: From 1994 to 2009, of 525 patients diagnosed with UC, with a median onset age of 42 years. The predominant form of UC was extensive colitis, which affected almost 33.3% (175/525), left-sided colitis was present in 21.3% (112/525) and rectum was present in 12.4% (65/525). The chronic relapsing type of UC was the most common (69.0%, 362/525), followed by the initial onset type (18.1%, 95/525), chronic continuous type with intermittent exacerbations (9.7%, 51/525), and acute fulminant type (3.2%, 17/525). Two hundred and twenty-one patients (42.1%, 221/525) were graded as mild, 162 (30.9%, 162/525) as moderate, and 142 (27.0%, 142/525) as severe UC. The proportion of mild colitis and rectum was significantly higher in patients with an onset age of over 60 years, compared with those with an onset age of less than 30 years (P < 0.05). The proportion of UC patients with old age onset (P < 0.05), male sex (P < 0.01), mild colitis (P < 0.01), rectum (P < 0.01), relapse-free type (P < 0.01) demonstrated a chronological increase from 1994 to 2009. CONCLUSIONS: The distinctive clinical features and chronological change were seen in UC patients in recent years. Compare to those with an onset at less than 30 years, the proportion of mild colitis and rectum was significantly larger in patients with an onset at over 60 years of age, and the proportion of UC patients with old age onset, male sex, mild colitis, rectum, relapse type were less.

[The significance of cough reflex sensitivity test in chronic cough].

OBJECTIVE: Preliminary study of the cough reflex sensitivity test in chronic cough patients with different gender, disease duration and causes to evaluate the clinical diagnostic significance of the test and further provide some information for the treatment of chronic cough. METHODS: Totally 108 chronic cough patients in our hospital were enrolled in the study with the final diagnosis of upper airway cough syndrome (UACS), cough variant asthma (CVA) and gastroesophageal reflux cough (GERC). They all went through the cough reflex sensitivity test and the retrospective analysis of the results was made. RESULTS: In 108 patients with chronic cough (76 UACS, 19 CVA and 13 GERC), lgC5 was significantly slower in the female (1.80) than the male (2.40, P < 0.05) and in the patients with cough duration over 12 months (1.80) than those with cough duration under 12 months (2.40, P < 0.05). Cough sensitivity in patients with different causes was significantly different (P < 0.05) with lower lgC5 in GERC patients (1.49) than CVA (2.40, P < 0.05) and UACS (2.40, P < 0.05) patients. CONCLUSIONS: Cough sensitivity is different in chronic cough patients with different gender, disease duration and causes. Cough reflex sensitivity test is of great value in the etiology diagnosis of chronic cough.

Effect of carbocisteine on acute exacerbation of chronic obstructive pulmonary disease (PEACE Study): a randomised placebo-controlled study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by airflow limitation, and has many components including mucus hypersecretion, oxidative stress, and airway inflammation. We aimed to assess whether carbocisteine, a mucolytic agent with anti-inflammatory and antioxidation activities, could reduce the yearly exacerbation rate in patients with COPD. METHODS: We did a randomised, double-blind, placebo-controlled study of 709 patients from 22 centres in China. Participants were eligible if they were diagnosed as having COPD with a postbronchodilator forced expiratory volume in 1 s (FEV(1)) to forced vital capacity (FVC) ratio (FEV(1)/FVC) of less than 0.7 and an FEV(1) between 25% and 79% of the predicted value, were aged between 40 and 80 years, had a history of at least two COPD exacerbations within the previous 2 years, and had remained clinically stable for over 4 weeks before the study. Patients were randomly assigned to receive 1500 mg carbocisteine or placebo per day for a year. The primary endpoint was exacerbation rate over 1 year, and analysis was by intention to treat. This trial is registered with the Japan Clinical Trials Registry (http://umin.ac.jp/ctr/index/htm) number UMIN-CRT C000000233. FINDINGS: 354 patients were assigned to the carbocisteine group and 355 to the placebo group. Numbers of exacerbations per patient per year declined significantly in the carbocisteine group compared with the placebo group (1.01 [SE 0.06] vs 1.35 [SE 0.06]), risk ratio 0.75 (95% CI 0.62-0.92, p=0.004). Non-significant interactions were found between the preventive effects and COPD severity, smoking, as well as concomitant use of inhaled corticosteroids. Carbocisteine was well tolerated. INTERPRETATION: Mucolytics, such as carbocisteine, should be recognised as a worthwhile treatment for prevention of exacerbations in Chinese patients with COPD.

Detection and characterization of hepatocellular carcinoma in rats with liver cirrhosis: diagnostic value of combined use of MR positive and negative contrast agents.

BACKGROUND: Gadolinium-enhanced multi-phase dynamic imaging has improved the accuracy of the diagnosis of hypervascular hepatocellular carcinoma (HCC), but using gadolinium-enhanced dynamic imaging alone is problematic in evaluating hypovascular HCC. This work aimed at evaluating the combined use of superparamagnetic iron oxide (SPIO)-enhanced and gadolinium set in distinguishing HCCs from regenerative nodules (RNs) in a rat model induced by diethylnitrosamine (DEN). METHODS: DEN-induced HCC model rats (n=40) and control rats (n=10) were studied. From weeks 16 to 19 after DEN administration, 4 animals were scanned every week. The hepatic changes were tested with a 1.5 Tesla magnet, and MR images of SPIO-enhanced and gadolinium set were obtained. According to the pathologic changes, the tumorigenesis was divided into HCC and RN (diameter of nodules > or =3 mm). Diagnostic accuracy of the combined SPIO-enhanced and gadolinium set and the gadolinium set alone was evaluated using receiver-operating characteristic curves. Sensitivity and specificity of the combined SPIO-enhanced and gadolinium set and the gadolinium set alone were calculated. RESULTS: The listed tests were completed in 29 rats (21 treated and 8 controls). One hundred and six nodules (82 HCCs, 24 RNs) were analyzed. The Az value and sensitivity with the combined SPIO-enhanced and gadolinium set (Az 0.94, sensitivity 0.96) were higher than those with the gadolinium set alone (Az 0.92, sensitivity 0.89). Using the combined SPIO-enhanced and gadolinium set led to detection of 6 nodules which were negative in the gadolinium set alone and 3 nodules were correctly characterized. CONCLUSION: Using the combined SPIO-enhanced and gadolinium set improved the detectability of HCCs and the SPIO-enhanced imaging compensated for the gadolinium set in differentiating HCCs from RNs in a rat model.

[The effects of dendritic cells overexpressing Serrate1 on the differentiation of CD4(+)CD25(+) T cells in asthmatic mice].

OBJECTIVE: To observe the effects of dendritic cells (DCs) overexpressing Serrate1 on the differentiation of CD(4)(+)CD(25)(+) T cells and the production of inhibitory cytokines in asthmatic mice. METHODS: Asthma mouse model was established by the routine method. After intravenous injection of the DCs transfected with Serrate1 into the naïve mice, the airway and lung inflammation was observed and the count of CD(4)(+)CD(25)(+) T cells delivered from the spleen and the percentage accounting for CD(4)(+)T cells were measured by flow cytometry. The expression of IL-10, transforming growth factor (TGF)beta1, and cytologic T-lymphocyte-associated antigen (CTLA)-4 mRNA of CD(4)(+) T cells were detected by RT-PCR. RESULTS: Compared with the non-transfected group, the airway inflammation of asthmatic mice injected the DCs transfected with Serrate1 reduced significantly, the number of CD(4)(+)CD(25)(+) T cells delivered from the spleen and the percentage accounting for CD(4)(+) T cells and the expression of IL-10, TGFbeta1, and CTLA-4 mRNA of CD(4)(+) T increased. CONCLUSIONS: DCs overexpressing Serrate1 could induce the differentiation of the CD(4)(+)CD(25)(+) T cells and increase the production of inhibitory cytokines in asthma in vivo, indicating that Notch1/Serrate1 signal pathway of DCs plays an important role in the induction of immune tolerance of T cells to allergens.

[Current status of prevention and management of chronic obstructive pulmonary disease in rural area in China].

OBJECTIVE: To investigate the current status of prevalence, prevention and management of chronic obstructive pulmonary disease (COPD) in rural area in China. METHODS: A cross-sectional survey of COPD was conducted in Beijing city, Shanghai city, Guangdong province, Liaoning province, Tianjin city, Chongqing province and Shanxi province. A population-based cluster sample was randomly selected from each rural area. In the selected community, all residents at least 40 years old were recruited, and interviewed with a modified standardized questionnaire from the international burden of obstructive lung diseases (BOLD) study. All participants were tested with spirometry. Those with airflow limitation were performed on post-bronchodilator spirometry. The post-bronchodilator a ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC) less than 70% was defined as the diagnostic criteria of COPD. RESULTS: (1) Data of 9434 participants was valid for analysis, with a valid response rate of 83.6%; the prevalence of COPD in rural was 8.8% (830/9434), 12.8% in male and 5.4% in female. (2) The percentage of smoking and the exposure to biomass smoke in rural was 43.0% (4059/9434) and 83.1% (7835/9434) respectively; cigarettes cessation rate was 17.5%; only 12.4% (502/4059) of smokers had received advice to quit smoking. (3) Among COPD patients, only 30.0% (249/830) had ever been diagnosed as COPD, bronchitis, emphysema, or asthma, 2.4% (20/830) had ever received spirometric tests, and 74.5% were current smokers; only 7.9% (50/634) COPD patients in stage two or over had received regular drug treatment. CONCLUSION: There was high prevalence and poor prevention and management for COPD in rural areas. Therefore, an enforced prevention and management for COPD are urgent.

[Immunoregulatory role of 1, 25-dihydroxyvitamin D(3)-treated dendritic cells in allergic airway inflammation].

OBJECTIVE: To explore the mechanism and immunoregulatory role of 1, 25-dihydroxy vitamin D(3) [1, 25 (OH)(2)D(3)]-treated dendritic cells (DCs) in allergic airway inflammation. METHODS: Mouse bone marrow-derived DCs were treated by 1, 25 (OH)(2)D(3) for 72 h. The expression levels of different Notch ligands: Jagged1, Jagged2, Delta1, Delta3, and Delta4 in these DCs were detected by RT-PCR and Western blotting. Mouse spleen CD4+ T cells were cultured with 1, 25 (OH)(2)D(3)-treated DCs or 1, 25 (OH)(2)D(3)-treated DCs blocked by polyclonal antibody of Jagged1 or Jagged2 (control group) for 48 h. The percentage of CD4+CD25+Foxp3+ T cells in CD4+ T cells was detected by flow cytometry (FCM). Ten mice underwent intraperitoneal injection of ovalbumin (OVA) to be sensitized and then divided into 2 groups to inhale 1, 25 (OH)(2)D(3)-treated DC suspension and PBS-DC suspension respectively for 6 successive days. Then the mice were killed. Bronchoalveolar lavage fluid was obtained to detect the eosinophil count and the levels of interleukin (IL)-4, IL-6, IL-13, and interferon (IFN)-gamma, and pathological examination of lung was conducted. Spleens were taken out to isolate the CD4+ T cells, and immunolabeling and FCM were used to detect the percentage of CD4+CD25+Foxp3+ T cells. RESULTS: The mRNA and protein expression levels of Jagged1 and Jagged2 in the 1, 25 (OH)(2)D(3)-treated DCs were (0.376 +/- 0.029) and (0.786 +/- 0.034), and (0.564 +/- 0.018) and (0.632 +/- 0.026) respectively, all significantly higher than those of the control group [(0.146 +/- 0.032) and (0.124 +/- 0.025), and (0.267 +/- 0.012) and (0.098 +/- 0.012) respectively, all P < 0.01)]. The percentage of CD4+CD25+Foxp3+ T cells in the CD4+ T cells cultured with 1, 25 (OH)(2)D(3)-treated DCs was (22.49% +/- 0.56%), significantly higher than that of the a PBS control group [(6.67% +/- 0.60%), P < 0.01]. The percentage of CD4+CD25+Foxp3+ T cells in CD4+ T cells after cultured with 1, 25 (OH)(2)D(3)-treated DC blocked by polyclonal antibody of Jagged2 was (6.56% +/- 1.89%), significantly lower than that of the un-blocked control group [(20.37% +/- 1.64%), P < 0.01]. The levels of IL-4, IL-5, IL-13, and IFN-gamma, and eosinophil count in the BALF of the 1, 25 (OH)(2)D(3)-treated DC group were (33 +/- 5) pg/ml, (134 +/- 23) pg/ml, (91 +/- 11) pg/ml, and undetectable (< 12.5 pg/ml), and (236 +/- 29) x 10(3)/ml, all significantly lower than those of the PBS-DC group [(55 +/- 7) pg/ml, (332 +/- 49) pg/ml, (152 +/- 19) pg/ml, and (23 +/- 6) pg/ml, and (588 +/- 56) x 10(3)/ml, all P < 0.01]. The percentage of CD4+CD25+Foxp3+ T cells in the spleens of the 1, 25 (OH)(2)D(3)-treated DC group was (14.69% +/- 1.14%), significantly higher than that of the PBS-treated DC group [(2.38% +/- 0.14%, P < 0.01). CONCLUSION: Treatment of the DCs with 1, 25 (OH)(2)D(3) inhibits the allergic inflammation in the airway, maybe via the induction of CD4+CD25+Foxp3+ regulatory T cells by 1, 25 (OH)(2)D(3)-treated DCs through Jagged2-mediated Notch signal pathway.

[The quality of life of patients with chronic obstructive pulmonary disease and correlated factors].

OBJECTIVE: To evaluate the quality of life (QOL) of patients with chronic obstructive pulmonary disease (COPD) and correlated factors. METHODS: Data of 20 245 patients with COPD were collected from the cross-sectional survey of COPD, which was conducted between 2002 and 2004 in urban and rural areas of Beijing, Shanghai, Guangdong, Liaoning, Tianjin, Chongqing and Shanxi for residents aged over 40 years old. The recruited populations were interviewed with questionnaire and tested for spirometry. The quality of life was assessed with 12-item short-form health survey questionnaire (SF-12). Those with less than 70% of post-bronchodilator FEV(1)/FVC were identified as having COPD. The differences between groups in SF-12 scores converted by rank were compared using general linear model. Stepwise multiple linear regressions were conducted to study the main determinants of QOL. RESULTS: Compared to subjects without COPD, those with COPD had impaired QOL (56 +/- 7 vs. 57 +/- 6 in mental component scores, F = 4.442, P < 0.05; 46 +/- 9 vs. 50 +/- 6 in physical component scores, F = 453.960, P < 0.05). Among COPD patients, the mental component score was associated with scores of dyspnea, BMI, comorbidities, sex and living areas, while the physical component score was associated with scores of dyspnea, severity of COPD, comorbidities, exposure to dusts/gases/fumes, sex, age, educational level and previous diagnosis of respiratory diseases (all P < 0.05). CONCLUSIONS: The QOL in patients with COPD was impaired and associated with scores of dyspnea, severity of COPD, comorbidities and BMI. Improvement of dyspnea, nutritional support, prevention of comorbidities and keeping away from risk factors may improve the QOL in COPD patients.

Early-generated interneurons regulate neuronal circuit formation during early postnatal development.

A small subset of interneurons that are generated earliest as pioneer neurons are the first cohort of neurons that enter the neocortex. However, it remains largely unclear whether these early-generated interneurons (EGIns) predominantly regulate neocortical circuit formation. Using inducible genetic fate mapping to selectively label EGIns and pseudo-random interneurons (pRIns), we found that EGIns exhibited more mature electrophysiological and morphological properties and higher synaptic connectivity than pRIns in the somatosensory cortex at early postnatal stages. In addition, when stimulating one cell, the proportion of EGIns that influence spontaneous network synchronization is significantly higher than that of pRIns. Importantly, toxin-mediated ablation of EGIns after birth significantly reduce spontaneous network synchronization and decrease inhibitory synaptic formation during the first postnatal week. These results suggest that EGIns can shape developing networks and may contribute to the refinement of neuronal connectivity before the establishment of the adult neuronal circuit.

Regulatory T cells and asthma.

Asthma is a chronic disease of airway inflammation due to excessive T helper cell type 2 (Th2) response. Present treatment based on inhalation of synthetic glucocorticoids can only control Th2-driven chronic eosinophilic inflammation, but cannot change the immune tolerance of the body to external allergens. Regulatory T cells (Tregs) are the main negative regulatory cells of the immune response. Tregs play a great role in regulating allergic, autoimmune, graft-versus-host responses, and other immune responses. In this review, we will discuss the classification and biological characteristics, the established immunomodulatory mechanisms, and the characteristics of induced differentiation of Tregs. We will also discuss the progress of Tregs in the field of asthma. We believe that further studies on the regulatory mechanisms of Tregs will provide better treatments and control strategies for asthma.

Supramolecular glycorhodamine-polymer dot ensembles for the homogeneous, fluorogenic analysis of lectins.

We have developed a new series of glycoprobe-polymer dot ensembles for the fluorogenic, homogeneous detection of lectins. Electrostatic self-assembly between positively charged rhodamine-based glycosides and negatively charged poly(3-hexylthiophene-2,5-diyl)/poly(styrene-co-maleic anhydride) polymer dots produces the ensembles with a quenched fluorescence. Fluorescence spectroscopy showed that the ensembles exhibited a concentration-dependent fluorescence enhancement with selective lectins over a range of unselective lectins and proteins. This research provides insight into the development of simple fluorogenic probes for homogeneous lectin analyses based on the supramolecular assembly between polymeric nanoparticles and fluorescent glycoprobes.

Selective adsorption activities toward organic dyes and antibacterial performance of silver-based coordination polymers.

Two silver-based coordination polymers, [Ag2(bpy)2(cbda)] (BUC-51) and [Ag3(bpy)3(cpda)]·(NO3)·9H2O (BUC-52), have been successfully prepared by slow evaporation at room temperature. These coordination polymers exhibited good adsorptive performances toward series organic dyes with sulfonic groups, which could be ascribed to the AgcdotsO interaction between the silver(I) atoms in CPs and the oxygen atoms from sulfonic groups attached to organic dyes. Both BUC-51 and BUC-52 favoured slow release of Ag+ ions resulting into outstanding long-term antibacterial abilities toward Gram-negative bacteria, Escherichia coli (E. coli), which was tested by a minimal inhibition concentration (MIC) benchmark and an inhibition zone testing method. Both scanning electron microscope (SEM) and transmission electron microscope (TEM) images demonstrated that these two Ag-based coordination polymers could destroy the bacterial membrane and further cause death. Additionally, the excellent stability in common solvents and good optical stability under UV-visible light facilitated their adsorptive and antibacterial applications.