[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.

IKKε aggravates inflammatory response via activation of NF-κB in rheumatoid arthritis.

OBJECTIVE: Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disease, whereas its cause still remains elusive. Typical pathological manifestations of RA include persistent synovitis and bone degeneration in the surrounding joints. Although the incidence of RA is high in population, currently there have been no effective cures for it. The purpose of this study is to investigate the therapeutic effects and main mechanism of IKKε (inhibitor of nuclear factor kappa-B kinase ε) in collagen II induced- Rheumatoid Arthritis (CIA) mice model. MATERIALS AND METHODS: IKKε-/- and wild-type (WT) littermate control mice were intraperitoneally injected with 5 mg/kg collagen II monoclonal antibody cocktail (Cab) for 5 days. After that, the nociception threshold and clinical rheumatoid arthritis articular damage score of mice were evaluated. After 5 days-CAb treatment, serum levels of a series of inflammatory cytokines including interleukin-6 (IL-6), IL-1ß, tumor necrosis factor-α (TNF-α) and interferon (IFN) were detected with enzyme-linked immunosorbent assay (ELISA) in both groups. Besides, Real-time reverse transcription polymerase chain reaction (Real-time RT-PCR) was used to evaluate the expression of these inflammatory cytokines in plantar tissues. In addition, Western blot was performed to investigate the protein levels of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B) signaling pathway. Moreover, WT mice receiving CAb were further applied with or without IKK inhibitor amlexanox (25 mg/kg) to investigate the expression of the above-mentioned inflammatory cytokines. RESULTS: Our work showed that IKKε-/- mice with CIA displayed less nociception and suppressed inflammatory response than WT mice. Meanwhile, the clinical rheumatoid arthritis articular damage scores were significantly decreased in IKKε-/- mice. The levels of TNF-α, IL-1ß, IL-6 in serum and plantar tissues in IKKε-/- mice were significantly lower than those in WT mice. Besides, NF-κB expression in IKKε-/- mice was significantly decreased. Similarly, the same phenotype was observed in WT mice administrated with IKKε inhibitor amlexanox as that of IKKε-/- mice, indicating that inflammatory and nociception responses were remarkably decreased than those of the negative controls. CONCLUSIONS: IKKε plays an important role in promoting nociception and inflammatory response in CIA. Our research demonstrated that knockout of IKKε may serve as a new direction for clinical prevention and treatment of rheumatoid arthritis. IKKε inhibitor amlexanox may become a new drug for the treatment of rheumatoid arthritis.

[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.

[Treatment of liver cancer in vitro and in mice by monoclonal antibody targeting epithelial specific antigen-positive liver cancer stem cells in combination with cisplatin].

OBJECTIVE: To investigate the biological characteristics of monoclonal antibodies against human liver cancer stem cells and its therapeutic effect in combination with cisplatin in the treatment of hepatocellular carcinoma. METHODS: Cell culture in serum-free medium and PKH26 staining were used to determine the existence of cancer stem cells in human liver Bel7402-V3 cell line. The co-expression of antigen recognized by monoclonal antibody (McAb) 15D2 and epithelial specific antigen (ESA) and PKH26-positive cells in the Bel7402-V3 cells were detected by immunofluorescence assay. Serum-free suspension culture was used to detect the self-renewal ability of 15D2-positive Bel7402-V3 cells sorted by flow cytometry and the effect of 15D2 on the self-renewal ability of Bel7402-V3 cells. The effect of 15D2 on cisplatin resistance in the cells was examined by CCK8 method. The inhibitory effect of 15D2 combined with cisplatin on the transplanted tumor growth in mice was also observed. RESULTS: Single PKH26-positive cells were observed in the Bel7402-V3 cell spheroids cultured for 11 days. Immunofluorescence assay showed that the 15D2-recognized antigen could be conjugated with PKH26 and ESA and co-localized on Bel7402-V3 cells. The spheroid formation rate of 15D2-positive cells in serum-free medium was significantly higher than that of 15D2-negative cells [(30.4±3.4)% vs. (8.8±1.8)%, P<0.01]. The cisplatin resistance of 15D2-positive cells was obviously higher than that of 15D2-negative cells (IC50: 1.014 µmol/L vs. 0.365 µmol/L). McAb 15D2 significantly suppressed the spheroid formation of Bel7402-V3 cells, with an inhibition rate of 37.5%. McAb 15D2 also notably inhibited the cisplatin resistance of Bel7302-V3 cells. The IC50 was 0.211 µg/ml in the 15D2 group and 0.325 µg/ml in the control group. The mouse experiment showed that the tumor growth rates of 50 mg/kg, 25 mg/kg and 12.5 mg/kg 15D2-treatment groups were 82.6%, 71.4% and 60.0%, respectively; that of the 50 mg/kg 15D2 + cisplatin group was 91.0%, and that of the cisplatin monotherapy was 56.7%. CONCLUSION: McAb 15D2 is a functional monoclonal antibody targeting liver cancer stem cells, which could be a potential monoclonal antibody drug for the stem cell-targeted therapy of liver cancer.

Transoral obesity surgery: endoluminal gastroplasty with an endoscopic suture device.

BACKGROUND AND STUDY AIMS: Surgical creation of a small gastric pouch with a restricted outlet is a well-established option for the treatment of morbid obesity. This report describes initial experience with endoscopic transoral stomach partition using a newly designed suturing apparatus. MATERIALS AND METHODS: A fresh porcine stomach was placed in the Erlangen model. A prototype suture device, incorporating a curved needle and an intracorporeal tightening mechanism, was used in this procedure. A long fishing line was first introduced into the stomach, with the two ends left outside. The suturing device, premounted outside a standard gastroscope, was inserted into the stomach and delivered several stitches attaching the fishing line to both the anterior and posterior walls along the line for the stomach to be partitioned. Five throws of half-hitches were tied onto the fishing line extracorporeally and separately pushed into place, creating a gastric pouch just below the esophagogastric junction. A flexible sheath of 8 cm long was then put on one side of the fishing line and pushed into the stomach. Additional extracorporeal knots were tied on the fishing line, forming a restrictive ring at the outlet of the pouch. The ring was then anchored to the stomach wall with similar endosutures. RESULTS: The proximal gastric pouch, with an estimated volume of approximately 100 ml, was successfully created with a restrictive band at its outlet. All of the stitches were securely sutured, with consistent penetration of the muscular layer of the stomach wall. CONCLUSIONS: In a bench model, it is technically possible to accomplish transoral gastroplasty endoscopically with an intraluminal suturing device. Further live animal studies will be needed in order to confirm the efficacy and safety of this procedure before clinical application.

Assessing the adequacy of endoscopically tied knots: a functional approach.

BACKGROUND AND STUDY AIMS: Endoscopic intracorporeal knots have potentially enormous applications in endoscopic surgery. We describe a method for testing the security of various types of endoscopically tied knots using a vessel perfusion manometer system. METHODS: A 4-cm segment of porcine splenic artery was placed on the mucosal surface of a pig stomach. The two ends of the vessel were brought out through the gastric wall and connected to a two-way manometer. One end was also joined to a pressure infusion bag. The stomach was mounted in an Erlangen training model. A long 3/0 nylon thread, previously introduced into the submucosal layer of the stomach and encircling the vessel, was brought out from the mouth. Three-throw square knots, Mayo knots, "surgeon's" knots and five-throw square knots were tied and pushed into place using a cap attached to a gastroscope. The pressure at the two ends of the artery was compared. If the pressure could be increased to over 200 mm Hg at one end without a change in the other, the knot was considered secure. RESULTS: Each type of knot was tested 12 times under endoscopic vision. The range for mean knotting time was 3.4 - 4.5 minutes. Five-throw knots took significantly longer to tie than three-throw knots (P < 0.005). There was one loose knot in each of the three-throw and Mayo groups, and three each in the "surgeon's" and five-throw groups (P > 0.05). CONCLUSIONS: This system is a reliable model for testing intracorporeal knots tied endoscopically. A three-half-hitches square knot with 3/0 nylon, tied using a flexible endoscope and knot-tightening cap, can withstand pressure up to 200 mm Hg.

Purification of natural antikeratin autoantibodies from normal human serum and their effect on human keratinocytes cultured in vitro.

BACKGROUND: Antikeratin (AK) autoantibodies, circulating antibodies against epidermal keratins, have been detected in all normal human sera. However, direct evidence on the biological significance of AK autoantibodies is still lacking. OBJECTIVES: To purify AK autoantibodies from human serum and to make a preliminary study of their biological effects on human keratinocytes. METHODS: We first extracted keratin polypeptides from human stratum corneum and analysed their purity using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Next, a keratin affinity column was prepared with the extracted keratins, and AK autoantibodies were purified from pooled normal human serum. Antibodies obtained were identified with SDS-PAGE, enzyme-linked immunosorbent assay, immunoperoxidase staining, immunoelectron microscopy and Western blotting. The biological effect of AK autoantibodies on cultured human keratinocytes was studied using a DNA synthesis assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric determination and cell cycle analysis. RESULTS: On average, 1.83 +/- 0.24 mg of antibodies could be purified from 10 mL of pooled human serum. High-titre IgG (about 1 : 70) and low-titre IgM (about 1 : 30) AK autoantibodies were obtained. The DNA synthesis assay and MTT colorimetric determination demonstrated that AK autoantibodies have a significant dose-dependent inhibitory effect on cultured keratinocytes. Correlation coefficients in the two experiments were - 0.583 and - 0.797, respectively. Cell cycle analysis indicated that a small dose of AK autoantibodies leads to inhibition of proliferation of cultured keratinocytes, whereas a large dose of AK autoantibodies causes a visible hypodiploid peak, suggesting apoptosis of keratinocytes. CONCLUSIONS: The present research lays a solid foundation for further investigation into the biological significance of natural AK autoantibodies.

Assessment of plutonium exposure in the Enewetak population by urinalysis.

Since 1980, the inhabitants of Enewetak Atoll have been monitored periodically by scientists from Brookhaven National Laboratory for internally deposited radioactive material. In 1989, the establishment of fission track analysis and of a protocol for shipboard collection of 24-h urine samples significantly improved our ability to assess the internal uptake of plutonium. The purpose of this report is to show the distribution of plutonium concentrations in urine collected in 1989 and 1991, and to assess the associated committed effective doses for the Enewetak population based on a long-term chronic uptake of low-level plutonium. To estimate dose, we derived the plutonium dose-per-unit-uptake coefficients based on the dosimetric system of the International Commission on Radiological Protection. Assuming a continuous uptake, an integrated Jones's plutonium urine excretion function was developed to interpret the Enewetak urine data. The Appendix shows how these values were derived. The committed effective doses were 0.2 mSv, calculated from the 1991 average plutonium content in 69 urine samples.

Gastrointestinal absorption of plutonium by the Marshall Islanders.

The gastrointestinal absorption constant (f1) is a critical parameter in assessing systemic uptake following the ingestion of a radioactive material and in monitoring such intakes. This study addresses the latter, particularly for plutonium, and from environmental measurements derives an f1 value of 4 x 10(-4) for the Marshallese population. The uncertainty associated with the methodology and measurements used in this f1 value assessment is evaluated. This evaluation takes into account the results from 24-h urine samples and the particular lifestyle of the Marshallese. Plutonium intake resulting from soil consumption is a primary parameter in this evaluation; for this study, it was assumed to be 500 mg d(-1). The f1 value determined here is consistent with the values in ICRP Publication 67 of 5x10(-4) for ages 1 to adult, and is the same as that suggested by the NRPB.

Assessment of plutonium exposures in Rongelap and Utirik populations by fission track analysis of urine.

A nuclear device, code-named Bravo, detonated at Bikini Atoll at 6:45 a.m. on 1 March 1954, unexpectedly released a large amount of radioactivity. Over 40 years after this incident, the study of its impact on the radiological health and environmental safety of the residents of Rongelap and Utirik Atolls continues. In 1987, researchers at Brookhaven National Laboratory established a fission track analysis (FTA) method for low-level 239Pu urinalysis. Two years later, a new shipboard protocol was developed for collecting 24-h radiologically clean urine samples. The purpose of this paper is to update information on the FTA method for measuring low-levels of plutonium, and to summarize results on the distribution of 239Pu in the populations of Rongelap and Utirik between 1981-1991. Plutonium detection levels (99% confidence level) in these samples were 2-3 microBq, which is equivalent to 0.2-0.3 mSv effective dose equivalent (EDE) to age 70 for Marshallese. The latest 1991 FTA data indicate average EDE of 0.62 mSv and 1.6 mSv for the people of Rongelap and Utirik, respectively, which both are the highest values since 1988.