[An epidemiological survey on clinical features, self-management and cognitive level of elderly asthmatics in China].

Objective: To investigate the prevalence of asthma among the elderly people in China and to analyze the clinical features, self-management and cognitive level of elderly asthma patients. Methods: According to the multi-stage random cluster sampling methods, a total of 164 215 subjects were visited by a questionnaire in the last epidemiology survey from eight provinces (Beijing, Shanghai, Guangdong, Liaoning, Henan, Shanxi, Jiangsu, Sichuan provinces) and seven regions (north, northeast, southern china, east, south, southwest and northwest) in China from February 2010 to August 2012. 2 034 were diagnosed as asthma. The elderly patients aged ≥65 years were selected from the 2 034 asthma patients. The clinical characteristics, comorbidities, the status of asthma control and self-management and insights of the disease in elderly asthma patients were analyzed. Results: Among the 2 034 asthma patients, 584 (28.7%) were elderly asthmatics aged ≥65 years old and 1 450 (71.3%) were<65 years old. In the elderly asthma group, Early-onset asthma accounted for 439 (75.2%) and 145 (24.8%) were late-onset. The common clinical manifestations of elderly asthma patients were: chest distress 395 (67.6%), wheezing 304 (52.1%), cough 298 (51.0%). Common comorbidities of elderly asthmatics were: chronic obstructive pulmonary disease 144 (24.7%), allergic rhinitis 122(20.9%), gastroesopheal reflux disease (GERD) 114(19.5%), allergic conjunctivitis 86 (14.7%), eczema 82 (14.0%), chronic bronchitis 76 (13.0%). The Asthma Control Test (ACT) scores of elderly asthmatics and non-elderly asthmatics were (18.5±3.2) and (21.7±3.4) respectively. There was a significant difference between the two groups (P=0.042). Of the elderly asthmatics, only 13 (2.2%) patients monitored daily using a peak flow meter. 93 (15.9%) patients aware that asthma was characterized by chronic airway inflammation. 64 (11.0%) asthmatics understood that the treatment goal. Conclusions: The clinical manifestations of elderly asthmatics are atypical, especially paroxysmal wheezing. Asthma in elderly people causes more comorbidities and mortality. The self-management and cognitive level of patients with asthma needs to be improved.

[A survey on clinical characteristics and risk factors of severe asthma in China].

Objective: To investigate the clinical characteristics and risk factors of severe bronchial asthma in Chinese people over 14 years old. Methods: According to the multi-stage random cluster sampling methods, a total of 164 215 subjects were visited by a questionnaire in the epidemiology survey from eight provinces (Beijing, Shanghai, Guangdong, Liaoning, Henan, Shanxi, Jiangsu, Sichuan provinces) located in seven regions (north, northeast, east, central China, south, southwest and northwest) of China from February 2010 to August 2012. A total of 2 034 were diagnosed as asthma. The clinical characteristics and related risk factors of patients with severe asthma in China were analyzed. Results: Among all asthma patients, 560 were newly diagnosed, accounting for 27.5% (560/2 034) and the percentage of previously confirmed patients was 72.5% (1 474/2 034). A total of 145 were eligible for severe asthma, accounting for 9.8% (145/1 474) of previously confirmed asthmatics and 7.1% (145/2 034) of all asthmatics. 83.5% (121/145) severe asthmatics had at least one trigger factor. Correlation analysis showed that the risk factors of severe asthma were: smoking (OR=1.543, 95%CI: 1.250-1.814), obesity (OR=2.186, 95%CI: 1.972-2.354), petting (OR=2.135, 95%CI: 1.904-2.283), combined with allergic rhinitis (OR=3.456, 95%CI: 2.721-4.326), gastroesophageal reflux disease (OR=1.842, 95%CI: 1.682-2.140), bronchiectasis (OR=1.665, 95%CI: 1.347-1.912) or chronic obstructive pulmonary disease (OR=1.312, 95%CI: 1.171-1.694). Conclusions: The most common comorbidities in severe asthmatics in China are allergic rhinitis and gastroesophageal reflux disease. The risk factors of severe asthma include obesity, allergic rhinitis, gastroesophageal reflux disease, chronic obstructive pulmonary disease, bronchiectasis, smoking and petting.

[The mobilization effect of IL-25 on eosinophil progenitor cells in allergic asthma].

Objective: Eosinophil progenitor cells (EoP) play a critical role in allergic airway inflammation in asthma. Previous studies have revealed that the expression of IL-25 receptor subunits (IL-17RA and IL-17RB) are increased on eosinophils (Eos) from allergic asthmatics upon allergen inhalation but few study has explored the role of IL-25 on EoP. Thus, in this research we examined the possible role of IL-25 on EoP in allergic asthmatics challenged by allergen, as well as in animal models where we verified the changes of newly produced Eos after IL-25 knockout. Methods: Asthmatics (n=14, during 2017-2018) who developed allergen-induced early and late responses were enrolled in this study. Blood was collected at pre-and 24 h post-challenge. Surface expression of IL-17RA and IL-17RB were evaluated by flow cytometry on EoP. In vitro migration assay was used to examine migrational responses of EoP and hematopoietic cells (HPC) from these subjects. In animal models, mice were grouped according to whether IL-25 was knock-out and whether mice were sensitized and challenged by ovalbumin (OVA) into asthmatic, control, knockout asthmatic and knockout control groups. Lung tissues, bronchoalveolar lavage flow (BALF) and bone marrow tissues of these mice were collected in order to evaluate airway inflammation and amount of newly produced (Brdu positive) and mature Eos. Results: EoP expressing IL-17RB were significantly increased after allergen inhalation in allergic asthmatics [(514±138) vs. (1146±450)/10(6) cells, pre-and post-challenge, F=6.819, P=0.022]. Pre-exposure to IL-25 primed the migrational responsiveness of EoP to stromal cell-derived factor (SDF)1α [(39.0±10.1)% vs. (73.0±7.9)%, control and IL-25 exposure groups respectively, P=0.021, 95% CI 5.19%~58.45%]. In OVA sensitized mice, knockout of IL-25 significantly reduced Eos and newly produced Eos percentage in the BALF [Eos, (7.8±2.0)% vs. (3.1±0.6)%, asthmatic and knockout asthmatic group respectively, P=0.002, 95% CI-7.57% to -1.98%; Brdu positive Eos, (50.0±7.6)% vs. (8.6±4.3)%, asthmatic and knockout asthmatic group respectively, P=0.011, 95% CI-72.41% to -10.27%], and newly produced Eos were also reduced in the bone marrow [(70.8±6.1)% vs. (1.3±1.3)%, asthmatic and knockout asthmatic group respectively, P=0.000, 95% CI -94.88% to -44.18%]. Conclusion: These results suggest an important role of IL-25 in allergen-induced EoP migration, local differentiation and eosinophilia in the airways.

[Association of CYP19A1 gene rs7176005 single nucleotide polymorphism with breast cancer risk and clinicopathologic features of tumor].

Objective: The aim of this study was to investigate the association of the CYP19A1 rs7176005 single nucleotide polymorphism (SNP) with breast cancer risk and with clinicopathologic features of tumors. Methods: This study was conducted by including 138 patients with breast cancer (cancer group), those who diagnosed as primary breast cancer after operation by pathology. There were 293 cases in the group of benign breast disease which was presented as a solid mass by the color ultrasound and pathologically diagnosed as "fibroadenoma or adenosis" (benign breast disease group), the cases were paired with breast cancer patients by age±5 in the same period, and there were 259 cases in the group of healthy control who received routine physical examination during the same period and were paired with breast cancer patients by age±5 without any detection of breast related diseases (healthy control group) at West China hospital between September 2012 and November 2016. The CYP19A1 rs7176005 SNP was detected by a direct sequencing method. Hardy-Weinberg test was used to analyze the genetic balance of the 3 groups. Chi square test was used to compare the distribution of rs7176005 genotypes between the 3 groups, and the differences of clinicopathological features in breast cancer patients carrying different genotypes. Results: The ages of the breast cancer cases, the benign breast disease group and the healthy control group were (44.69±8.09), (42.33±11.44) and (41.92±9.61) years old, respectively. Hardy-Weinberg equilibrium test identified that the composition ratios of alleles C and T in breast cancer group, benign breast disease group and healthy group were not statistically significant (χ(2) values were 0.83, 0.34 and 0.04, respectively, P values were 0.363, 0.561, and 0.852, respectively). All the three groups met the genetic balance, had consistency and could represent the population. Among the 138 cases of breast cancer, the CYP19A1 rs7176005 SNP was significantly associated with the diameter of the tumor (P=0.031). The majority of tumor size was <2 cm in patients who carrying TT and CT genotypes, and the proportion was 75% (12/16) and 58% (40/69), respectively. While those patients with TT genotype were mainly >2 cm and ≤5 cm, and the proportion was 51% (27/53). The distribution of TNM stage among patients with different genotypes was also statistically significant (χ(2)=11.19, P=0.025). The most common stage was Ⅱ in Patients who carrying CC and CT genotypes, and the proportion was 45.3% (24/53) and 52.2% (36/69), respectively. While those patients with TT genotype was mainly in stage Ⅰ and the proportion was 56.3% (9/16). Conclusion: Though the CYP19A1 rs7176005 SNP is not associated with breast cancer development, breast cancer patients with the C allele exhibit a high tumor growth rate and large diameters.

Immunotolerant indoleamine-2,3-dioxygenase is increased in condyloma acuminata.

BACKGROUND: The tryptophan-depleting enzyme indoleamine-2,3-dioxygenase (IDO) is critical for the regulation of immunotolerance and plays an important role in immune-associated skin diseases. OBJECTIVES: To analyse the level of IDO in condyloma acuminata (CA) and its role in this condition. METHODS: IDO expression was assessed in the skin and peripheral blood of healthy controls and patients with CA. To assess the role of skin IDO in immunity, the ability of isolated epidermal cells to metabolize tryptophan and the influence on polyclonal T-cell mitogen (PHA)-stimulated T-cell proliferation were explored. RESULTS: IDO median fluorescence intensities in peripheral blood mononuclear cells from patients with CA were similar to those from healthy controls. Immunohistochemistry showed that IDO+ cells were rare in normal skin and the control skin of patients with CA, but were greatly accumulated in wart tissue. Most fluorescence signals of IDO+ cells did not overlap with those of CD1a+ Langerhans cells. Human papillomavirus (HPV) DNA probe in situ hybridization showed a large number of IDO+ cells in the HPV- site. Keratinocytes in the skin of healthy controls and the circumcised skin of patients with CA could minimally transform tryptophan into kynurenine, but IDO-competent epidermal cells from warts could transform tryptophan. In addition, these IDO-competent epidermal cells could inhibit PHA-stimulated T-cell proliferation. The addition of an IDO inhibitor, 1-methyl-d-tryptophan, restored the inhibited T-cell proliferation. CONCLUSIONS: Abnormally localized high IDO expression might be involved in the formation of a local immunotolerant microenvironment.

[Chinese expert consensus for non-antiinfective effects and clinical use of macrolides].

Important/potential value of macrolides has been proved in the management of chronic respiratory diseases by increasing basic and clinical trials.Through three face-to-face discussions, 10 experts examined important data and drafted this consensus related to macrolides: (1) mechanism of non-antiinfective effects; (2) clinical use in chronic respiratory diseases; (3) cautions of long-term use.The mechanism out of non-antiinfective effects includes anti-inflammatory effect, modifying airway secretion, immune-regulation related to antibacterial effect, corticoid saving effect and anti-viral effect.The efficacy of long-term use of low-dose macrolides is definitely confirmed in diffuse panbronchiolitis, chronic rhinosinusitis. It is considerably used in bronchiectasia, cystic fibrosis, severe asthma and chronic obstructive pulmonary disease. Further studies should be conducted in cryptogenic organizing pneumonia and respiratory viral infection. It should be paid attention to its possible adverse effects (including drug interactions, cardiac toxicity, ototoxicity and disturbance of intestinal flora) and drug resistance in long-term use.A Chinese consensus for non-antiinfective effects and clinical use of macrolides is developed for the first time, which aims to expand their rational use and the further research.

[The relationship between smoking status and epidermiology of asthma in people aged over 14 years in China].

Objective: To study the relationship between bronchial asthma and smoking status in Chinese people. Methods: Asthma epidemiological survey and stratified-cluster-random method survey were performed in residents over 14 years in 8 provinces (cities) of China from February 2010 to August 2012. Asthma was diagnosed based upon case history, clinical signs and lung function test. Smoking status was investigated by questionnaire. Results: Sampling population was 180 099 and 164 215 were valid. A total of 2 034 subjects were diagnosed as asthma including 79 692 men and 84 523 women. The overall prevalence rate of asthma was 1.24% (2 034/164 215). Smokers were 23.8% (39 137/164 215) in the whole population. Smokers were 34.5% (702/2 034) in asthmatic patients, compared with 23.7% (38 435/162 181) in no-asthmatic population. The incidence of asthma was 1.79% and 1.06% in smokers and non-smokers respectively (P<0.001), suggesting that OR of smoking was 1.70 (95% CI 1.55-1.86, P<0.001). According to asthma control test (ACT) score, the level of asthma control in non smoking group was higher than that in smoking group(43.2% vs 35.3%). The times of hospitalization due to acute exacerbations(0.51 vs 0.41 events/person/year), total hospitalization rate(27.35% vs 20.12%), annual emergency room visits (0.80 vs 0.60 events/person/year) and emergency room visit rate (31.77% vs 24.47%) were all much higher in smoking asthmatic patients than those in non smoking asthmatic patients, indicating that the level of asthma control in smoking patients was significantly worse than in non smoking patients. Conclusions: The smoking rate in Chinese people over 14 years is still high. The prevalence rate of asthma in smokers is significantly higher than that of non-smokers. The level of asthma control in smokers is significantly worse than that in non smokers.

[A cross-section study of severe asthma in eight provinces of China].

Objective: To analyze the prevalence of severe asthmain China. Methods: The epidemiological data was collected from 2 034 asthmatics who were diagnosed in the last epidemiological survey from 2009 to 2010 in 8 provinces. Results: According to the questionnaire survey, among the 2 034 patients, the previously diagnosed patients accounted for 72.47% (1 474/2 034) and the percentage of newly-diagnosed patients was 27.53% (560/2 034). In those 1 474 previously diagnosed asthmatics, 122 (8.28%) were classified into severe asthma, while 6.00% (122/2 034) of all asthmatics and 0.07% (122/164 215) of total respondents presented as severe cases. Statistically, there was no difference in the prevalence of severe patients between men and women. The morbidity rate of severe asthma was the lowest in the 21-30 year old group and the highest in 61-70 year old group (0.85% and 8.31% respectively). The difference among ages was statistically significant (χ2=18.791, P=0.005). In addition, the prevalence rates of severe asthma were also significantly diverged among patients with different education background(χ2=24.639, P<0.000 1). A negative relation was found between education level and the proportion of severe cases. Moreover, the morbidity of severe asthma in smoking patients and non-smoking patients were significantly different as well (χ2=7.447, P<0.05). Compared with asthma patients who do not smoke, smokers were more likely to suffer severe asthma (OR=1.663, 95% CI 1.150-2.404). Conclusions: The prevalence rate of severe asthma in China is similar to that in other countries.Elderly patients have higher risk of severe asthma. Smoking is considered as a risk factor for severe asthma.

[Gene typing and antibiotic resistance of methicillin-resistant Staphylococcus aureus isolated from lower respiratory tract at two hospitals in Shanghai].

OBJECTIVE: To study the genotyping characteristics and antibiotic resistance of methicillin-resistant Staphylococcus aureus(MRSA) isolated from lower respiratory tract at 2 different level hospitals in Shanghai. METHODS: The subjects included 155 patients at Ruijin Hospital and Tongren Hospital between January 2013 and June 2014, including 108 males and 47 females, with a mean age of 67.8±16.5. The 155 MRSA strains were isolated from lower respiratory tract specimens and multilocus sequence typing (MLST) and spa typing were analyzed by the PCR method. The antimicrobial resistance of MRSA was tested by VITEK-32. Fisher's exact test was used for statistical analysis. RESULTS: Among the 155 strains, 28 MLST-spa molecular types were identified, of which ST764-t002(41.29%), ST239-t037(17.42%) and ST239-t030(10.32%) were the most predominant types. The MRSA strains were susceptible to linezolid, vancomycin and teicoplanin, and also had a lower resistance to trimethoprim-sulfamethoxazole and rifampin, with a susceptible rate of 83.9% and 83.2% respectively, but were highly resistant to other antibiotics. The resistance rate of ST239-t037 to trimethoprim-sulfamethoxazole was higher than that of other types, and the resistance rate of ST239-t030 to rifampin was higher than that of other types, the differences being significant(P<0.001). The mean length of hospital stay of the 155 patients was (97±84) days, and mechanical ventilation were used in 78(50.3%) patients, while 108(69.7%))patients received invasive procedures. Broad-spectrum antibiotics were used in 136 (87.1%) patients. There were differences in age, hospitalization days, smoking history, history of COPD, mechanical ventilation, and operation between the 2 hospitals(P<0.05). CONCLUSION: Most of the MRSA strains at Ruijin Hospital and Tongren Hospital between January 2013 and June 2014 were multi-drug resistant, and the susceptibility spectrum of different genotypes was different.

Obvious emphysema on computed tomography during an acute exacerbation of chronic obstructive pulmonary disease predicts a poor prognosis.

BACKGROUND: Emphysematous change on computed tomography (CT) during the stable phase of chronic obstructive pulmonary disease (COPD) is reported to correlate with COPD prognosis. Acute exacerbation of COPD (AECOPD) is associated with a high risk of mortality and a poor prognosis. AIMS: This study aims to study the relationship between prognosis and emphysematous changes on CT during an AECOPD. METHODS: Histories were recorded, and CT acquired for 106 patients who visited the emergency department for an AECOPD. Emphysematous change was quantified by measuring the percentage of low-attenuation areas (LAA%) in the entire lung on CT images with a threshold of -950 Hounsfield units. Other factors that could influence AECOPD prognosis were also recorded on admission and analysed. At follow ups conducted in 1 year, patient survival, the modified Medical Research Council (mMRC) Dyspnoea Scale, and performance status (PS) were evaluated, and a COPD Assessment Test (CAT) was completed. RESULTS: The 1-year follow up was completed by 103 of 106 patients. The median LAA% was significantly higher in non-survivors (11%, n = 16) than in survivors (5.69%, n = 87) (P = 0.006) at the 1-year follow up. LAA% was significantly correlated with mMRC grade (r = 0.285, P = 0.008), PS (r = 0.397, P < 0.001) and CAT score (r = 0.27, P = 0.017) at the 3-month follow up, and with mMRC grade (r = 0.405, P < 0.001) and PS (r = 0.377, P < 0.001) at the 1-year follow up. LAA% > 7.5% was a significant predictor of 1-year mortality, higher mMRC and PS at the 3-month and 1-year follow ups, after adjustment for other prognostic predictors. CONCLUSION: Obvious emphysematous changes on CT (LAA% > 7.5%) during an AECOPD predicts a poor prognosis independent of other known indicators.

Association of xeroderma pigmentosum group D (Asp312Asn, Lys751Gln) and cytidine deaminase (Lys27Gln, Ala70Thr) polymorphisms with outcome in Chinese non-small cell lung cancer patients treated with cisplatin-gemcitabine.

Xeroderma pigmentosum group D (XPD) plays a key role in the repair of DNA and platinum resistance lesions. Cytidine deaminase (CDA) genes determine the velocity of gemcitabine catalysis. This study aimed to investigate the relationship between XPD and CDA genotypes and outcome in non-small lung cancer (NSCLC) patients. We used polymerase chain reaction-restriction fragment length polymorphism to evaluate genetic polymorphisms of XPD (Asp312Asn and Lys751Gln) and CDA (Lys27Gln and Ala70Thr) in 93 NSCLC patients treated with a cisplatin-gemcitabine regimen. There were no significant correlations between the XPD polymorphisms Asp312Asn and Lys751Gln with clinical benefits (P>0.05). Time to progression (TTP) did not differ between patients with wild type genotypes and those heterozygous for the single nucleotide polymorphism loci of XPD. However, a significant difference was observed in overall survival (OS) between XPD Asp312Asp and XPD Asp312Asn individuals (20.0 vs 12.4 months, P=0.04). Furthermore, the OS of patients with wild type genotypes was longer (20.5 months) than that of patients carrying the XPD 751Lys/Gln polymorphism (11.5 months). No significant differences in TTP or OS were observed in patients carrying different genotypes of CDA Lys27Gln, and no mutations were observed at the CDA Ala70Thr site. These results provide suggestive evidence of a favorable effect for the XPD 312Asp/Asp and XPD 751Lys/Lys genotypes with respect to overall survival rates in platinum-treated NSCLC patients. However, the CDA 27 polymorphism does not appear to affect the efficacy of gemcitabine.

Gender difference in protein expression of vascular wall in mice exposed to chronic intermittent hypoxia: a preliminary study.

Obstructive sleep apnea (OSA) is an independent risk factor for cardiovascular diseases such as systemic arterial hypertension, ischemic heart disease, stroke, heart failure, atrial fibrillation, and cardiac sudden death. The pathogenesis of cardiovascular disease in OSA is thought to be induced primarily by chronic intermittent hypoxia (CIH), a specific pattern of change in oxygenation during sleep. However, the underlying mechanisms of CIH-induced vasculature injury and gender differences are not well documented. The iTRAQ Quantitative Proteomic method enables analysis of a number of different proteins among several groups. Thus, we explored gender differences in protein expression in the vascular walls of mice exposed to CIH. C57BL/6J mice of each gender were exposed to CIH with a fractional inspired O2 (FiO2) nadir of 5% or control, with a treatment time of 8 h/day for 28 days. Differential proteins related to CIH-induced vascular injury between genders were identified using iTRAQ proteomic technology. A total of 163 proteins were identified, of which 34 showed significant differences between genders, which may correlate with vascular injury by CIH. Twenty up-regulated proteins and 14 downregulated proteins were observed in female mice compared with male mice. We identified different vascular proteins expressed under CIH between genders, suggesting that these proteins may be biomarkers of vascular injury by CIH.

Hypoxia induces dysregulation of local renin-angiotensin system in mouse Lewis lung carcinoma cells.

The renin-angiotensin system (RAS) influences cancer biology and is frequently dysregulated in malignancy. However, regulation of tumor local RAS remains poorly understood. Hypoxia is a hallmark of solid tumors and affects nearly every major aspect of cancer biology. Previous studies have shown that hypoxia can regulate RAS expression in somatic tissues and cells. The aim of this study was to investigate the influence of hypoxia on local RAS expression in mouse Lewis lung carcinoma (LLC) cells. For hypoxia treatment, LLC cells were cultured in a hypoxia incubator or treated with hypoxia-mimetic cobalt chloride. Hypoxia up-regulated angiotensin II, angiotensin-converting enzyme (ACE), and angiotensin II type 1 receptor (AT1R), and down-regulated ACE2 and angiotensin II type 2 receptor in LLC cells. Captopril, an ACE inhibitor, and losartan, an AT1R blocker, decreased expression of ACE and AT1R, but increased expression of ACE2 and angiotensin II type 2 receptor in LLC cells under hypoxia. Captopril and losartan also suppressed vascular endothelial growth factor-A expression in LLC cells under hypoxia. These findings suggest that hypoxia induces dysregulation of local RAS in LLC cells. The pathophysiological importance of hypoxia-induced RAS dysregulation and potentially therapeutic effects of RAS inhibitors on hypoxic tumor cells should be further examined.

Meta-analysis demonstrates lack of association between the ACE gene I/D polymorphism and obstructive sleep apnea-hypopnea syndrome occurrence and severity.

Published data on a possible association between the angiotensin-converting enzyme (ACE) gene I/D polymorphism and obstructive sleep apnea-hypopnea syndrome (OSAHS) occurrence and its severity risk are inconclusive. We performed a meta-analysis of case-control studies published in English or Chinese. Thirteen studies, totaling 1361 cases and 1373 controls, were investigated for association of the ACE I/D polymorphism with OSAHS. We also made a study of ACE I/D with OSAHS severity risk, including 879 mild/moderate OSAHS patients and 357 severe OSAHS patients. A random-effects model was used, irrespective of between-study heterogeneity. Study quality was assessed in duplicate. Overall, the ACE I/D polymorphism was not significantly associated with an increase in OSAHS risk [odds ratio (OR) = 1.21; 95% confidence interval (95%CI) = 0.88-1.65; P = 0.24]. In subgroup analysis by ethnicity, comparison of alleles I with D demonstrated a 58% (nonsignificantly) increased risk for OSAHS in Chinese (OR = 1.58; 95%CI = 0.92-2.70; P = 0.09). We also found that there was no significant association between ACE I/D and OSAHS severity risk. No publication biases were observed. This meta-analysis suggests that there is no significantly increased risk for OSAHS occurrence or severity associated with the ACE I/D polymorphism.

Study of the mechanisms by which Sambucus williamsii HANCE extract exert protective effects against ovariectomy-induced osteoporosis in vivo.

UNLABELLED: The purpose of this study is to investigate the dose-dependent effects of SWH on bone properties and the mechanism involved in mediating the osteoprotective actions of SWH. The results indicated that SWH could improve bone properties by inhibiting the process of bone resorption and stimulating the process of bone formation. INTRODUCTION: Our previous study showed that Sambucus williamsii HANCE (SWH) improved trabecular bone mass and cortical bone strength in ovariectomized (OVX) rats. The purpose of this study is to investigate the dose-dependent effects of SWH on bone properties and the mechanism involved in mediating the osteoprotective actions of SWH. METHODS: Three-month-old C57BL/6J mice were fed a phytoestrogen-free diet and subjected to either ovariectomy or sham operation. OVX mice were treated with genistein (50 mg/kg), or a low (200 mg/kg), medium (500 mg/kg), or high (1,000 mg/kg) dose of SWH extract. RESULTS: SWH could dose-dependently decrease urinary Ca excretion and increase serum Ca level in OVX mice. It could increase tibial bone mineral density and exert beneficial effects on the microarchitecture of trabecular bone in the OVX mice. SWH suppressed the ovariectomy-induced expression of Cbfa1 mRNA and cathepsin K mRNA and enhanced the ratio of OPG/RANKL mRNA expression in the tibia. In vitro study showed that SWH dramatically reduced the number of TRAP-positive cells in RANKL-induced RAW 264.7 cells. CONCLUSIONS: The present study indicated that SWH could improve bone properties by inhibiting the process of bone resorption and stimulating the process of bone formation.

Coexisting sharp ductal angulation with intrahepatic biliary strictures in right hepatolithiasis.

OBJECTIVE: To investigate the clinical characteristics of a coexisting sharp ductal angulation (< 90 degrees) with biliary stricture and to evaluate the difficulties it imposes in the management of retained or recurrent hepatolithiasis. DESIGN: Case-controlled study. SETTING: A referral center. PATIENTS: Eighteen consecutive patients having right-sided hepatolithiasis and a coexisting sharp ductal angulation associated with biliary stricture (group 1) were compared with 84 patients matched with sex, age, and conditions of hepatolithiasis and intrahepatic biliary stricture(s) but no sharp angulated duct (group 2). INTERVENTION: Postoperative cholangioscopic management (electrohydraulic lithotripsy or other lithotripsy, lithotomy, balloon dilation, biopsy, etc, via T-tube tract or percutaneous transhepatic route). MAIN OUTCOME MEASURES: Sessions of manipulations, incidence of complications associated with interventions or disease, and mortality were compared. RESULTS: Patients of group 1 needed more sessions of postoperative manipulation of stones and strictures (13.7 +/- 4.2 vs 8.0 +/- 2.3; P < .001). During management, there was a significantly increased vulnerability of severe and/or recurrent cholangitis (66.7% vs 9.5%; P < .001), septic shock (77.8% vs 11.9%; P < .001), liver abscess (55.6% vs 7.1%; P < .001), or massive hemobilia (33.3% vs 7.4%) in group 1 than in group 2. Their risks of coexisting secondary biliary cirrhosis (55.6% vs 9.5%; P < .001) and/or cholangiocarcinoma (16.6% vs 2.4%; P < .04) and mortality (27.8% vs 4.8%; P < .01) were also significantly higher in group 1. CONCLUSION: Our results suggest that the coexisting sharp ductal angulation with biliary strictures in right-sided hepatolithiasis is a distinct difficult clinical entity in the field of biliary tract calculi.

[Lung biopsies with light microscopic and ultrastructural observations in 34 cases of diffuse pulmonary diseases].

Lung biopsies with light microscopic and ultrastructural observations were performed in 34 cases of diffuse pulmonary diseases. Open lung biopsy 2 cases, transfiberoptic bronchoscopy lung biopsy 32 cases. There were 19 (56%) idiopathic interstitial fibrosis, 3 (9%) pulmonary alveolar proteinosis, 3 (9%) pulmonary sarcoidosis, 1 (3%) idiopathic pulmonary hemosiderosis, 2 (6%) pulmonary mycosis, 1 (3%) alveolar cell carcinoma, 2 (6%) pulmonary tuberculosis and 3 (9%) pulmonary collagen diseases. Diagnosis was based on clinical data and pathologic manifestation. Lung biopsy with light and electronic microscopic examination is useful in etiologic diagnosis and differential diagnosis for diffuse pulmonary diseases.

[Preventive effect of cardiomyopeptidin on rat heart injured by ischemia-reperfusion].

OBJECTIVE: To investigate the preventive effect of cardiomyopeptidin of small molecular weight polypeptide on rat hearts injured by ischemia-reperfusion. METHODS: In a rat model injured by ischemia-reperfusion in the heart, observation was made on the influence of cardiomyopeptidin on the activities of creatine kinase (CK) and lactate dehydrogenase(LDH), as well as on the content of MDA in plasma after the preventive drug was used. RESULTS: Cardiomyopeptidin could obviously prevent the injury caused by ischemia-reperfusion, reduce the activities of CK and LDH and the content of MDA in a dose-dependent manner. CONCLUSION: Cardiomyopeptidin has a preventive effect on myocardium injured by ischemia-reperfusion and this may be related to its reducing the release of myocardial enzyme and anti-lipoperoxidation.

4-1BB ligand-mediated imbalance of helper 17 T cells and regulatory T cells in patients with allergic asthma.

OBJECTIVES: To investigate the presence of 4-1BB ligand (4-1BBL) in the peripheral blood of patients with allergic asthma and evaluate its role in controlling the balance between helper 17 T (T(h)17) and regulatory T (T(reg)) cells. METHODS: Soluble 4-1BBL (s4-1BBL) was quantified by enzyme-linked immunosorbent assay in plasma from patients with asthma (n = 45) and from healthy control subjects (n = 35). The proportion of monocytes positive for membrane-bound 4-1BBL (m4-1BBL) was determined by flow cytometry. Peripheral blood mononuclear cells from patients with asthma were incubated with anti-4-1BB monoclonal antibody in vitro. Concentrations of interleukin (IL)-17 and transforming growth factor (TGF)-ß(1) in the culture supernatant were analysed. RESULTS: Plasma s4-1BBL concentrations and the proportion of m4-1BBL-positive monocytes were significantly lower in patients with asthma than in control subjects. The culture supernatant concentration of TGF-ß(1) was increased and that of IL-17 was decreased by incubation with anti-4-1BB monoclonal antibody. CONCLUSIONS: Both soluble and membrane-bound 4-1BBL were reduced in patients with allergic asthma compared with control subjects. 4-1BBL/4-1BB signalling may play an important role in allergic asthma by regulating the T(h)17/T(reg) balance.

New insights into the regulation of megakaryocytopoiesis by haematopoietic and fibroblastic growth factors and transforming growth factor beta 1.

Effects of cytokines on murine megakaryocyte (MK) colony formation from either unfractionated marrow cells or purified early haematopoietic cells were studied. Recombinant interleukin-3 (IL3), interleukin-6 (IL6), granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin (Epo) and acidic and basic fibroblast growth factor (aFGF and bFGF) each was able to stimulate MK colony growth although they varied somewhat in their potential. IL6 and FGFs, in addition to their effect on MK colony growth, increased the size of individual MK. The combination of IL3 with IL6 or FGF resulted in an additive action. Monoclonal anti-IL6 antibody completely neutralized the activity of mouse IL6 and FGFs but had no effect on human IL6, mouse IL3 and GM-CSF. When using purified lineage negative marrow cells, only IL3 and IL6 promoted MK colony formation. Transforming growth factor beta 1 (TGF-beta 1) at 10-200 pg/ml selectively inhibited IL3-induced MK colony formation, and at 0.2-0.5 ng/ml it still had no obvious effect on the activity of IL6 or GM-CSF but caused an inhibition of FGF-induced MK colony formation. These data suggest that differential mechanisms are involved in the regulation of megakaryocytopoiesis by IL3, IL6, FGFs and GM-CSF, and that TGF-beta 1 negatively regulates MK development mainly by interfering with the action of IL3.