脂肪酸合成酶参与骨肉瘤侵袭转移的研究进展

骨肉瘤患者致死的最主要因素为肺转移,而脂肪酸合成酶(FASN)与骨肉瘤侵袭转移关系紧密。FASN与骨肉瘤细胞之间存在双向正反馈作用,并在骨肉瘤的生长、分化、增殖、侵袭、凋亡等过程中起着关键作用。FASN可通过激活ERK1/2/Bcl-xL和HER2/PI3K/AKT信号通路或者介导microRNA和异质核核糖核蛋白A1来参与肿瘤细胞的增殖、转移等进展过程。FASN抑制剂如TVB-2640和安洛替尼等将在未来的骨肉瘤治疗中发挥重要的作用。

极光激酶B在骨肉瘤侵袭与转移中的作用研究进展

极光激酶B(Aurora-B)是一种有丝分裂的丝氨酸/苏氨酸蛋白激酶,隶属于极光激酶家族,参与细胞周期的完成。近年来,越来越多的研究发现Aurora-B参与多种肿瘤的侵袭和转移。在骨肉瘤中,Aurora-B可通过介导NPM1的磷酸化、microRNA、mTOR/ULK1、PI3K/Akt/NF-κB等多种方式,参与调控骨肉瘤的侵袭和迁移。文章就Aurora-B的生物学特性及其在骨肉瘤侵袭与转移中作用的研究进展进行综述。

波生坦联合西地那非治疗COPD并发肺动脉高压的疗效及对患者心肺功能的影响

目的:研究波生坦联合西地那非治疗COPD并发肺动脉高压的疗效及对患者心肺功能的影响。方法:选择124例COPD合并肺动脉高压患者作为观察对象,依据不同治疗方案分成对照组(n=59)和实验组(n=65)。对照组采用波生坦联合万他维治疗,实验组采用波生坦联合西地那非治疗,持续治疗3个月。对比两组患者治疗前后肺动脉压、心功能及肺功能变化。结果:治疗后两组患者的平均肺动脉压均低于治疗前,且实验组低于对照组,差异有统计学意义(P <0. 05);治疗后两组患者的心功能指标6MWD、RVEF水平均高于治疗前,且实验组高于对照组,差异有统计学意义(P <0. 05);治疗后两组患者的肺功能指标FEV1、FVC、FEV1/FVC水平均高于治疗前,且实验组高于对照组,差异有统计学意义(P <0. 05)。结论:波生坦联合西地那非治疗COPD并发肺动脉高压疗效显著,能有效降低肺动脉压,促进心功能、肺功能恢复,值得临床推广。

Asymptomatic patients of chronic obstructive pulmonary disease in China

Background Chronic obstructive pulmonary disease （COPD） has a variable natural history and not all individuals follow the same course. This study aimed to identify the prevalence and characteristics of asymptomatic COPD patients from a population-based survey in China.Methods A multistage cluster sampling strategy was used in a population from seven different provinces/cities. All residents （over 40 years old） were interviewed with a standardized questionnaire and spirometry.Post-bronchodilator forced expiratory volume in 1 second （FEV1）/forced vital capacity （FVC） of less than 70% was defined as the diagnostic criterion of COPD. All COPD patients screened were divided into symptomatic group and asymptomatic group according to the presence or absence of chronic respiratory symptoms. Socio-demographic,personal and exposure variables were collected and analyzed.Results Among the 1668 patients who were diagnosed with COPD from the 25 627 sampling subjects, 589 （35.3%）were asymptomatic. The age, sex, body mass index （BMI）,rural and urban distributions, smoking habit and education levels were similar in the two groups. A total of 64.7% of the asymptomatic patients had no comorbidities. Cardiovascular diseases and lung cancer were more common among symptomatic COPD patients than asymptomatic group.Asymptomatic COPD group were less likely to present with poor ventilation in the kitchen, a family history of respiratory disease and recurrent childhood cough. Asymptomatic COPD patients had significantly higher FEV1 （73.1% vs. 61.0%）, FVC （91.9% vs. 82.0%）, and a higher ratio of FEV1/FVC （62.9% vs.58.7%） （all P 〈0.001） than symptomatic group. More asymptomatic patients were underdiagnosed （91.9% vs.54.3%, P〈0.001） than symptomatic patients.Conclusions This large population-based survey confirmed a high prevalence of asymptomatic COPD patients in China. More use of spirometry screening test may be important to the early detection of COPD.

Allergen micro-array detection of specific IgE-reactivity in Chinese allergy patients

Background Allergen micro-arrays are powerful tools for screening of serum IgE-reactivity. In this study allergen micro-arrays were used to identify dominating IgE-binding allergens and cross-reactivity patterns among selected Chinese allergy patients. Methods The study was conducted using patient sera from the cities of Guangzhou, Nanjing, Chengdu and Shenyang. In total 100 sera with Dermatophagoides pteronyssinus （Der p） specific IgE-levels higher than 50 kU/L were selected for testing against 103 individual allergens. Results Among 100 selected patients, 95% showed IgE-reactivity towards house-dust mite allergens Dermatophagoides farinae （Der f） 1, Der f 2 and Der p 2 and 94% were IgE positive against Der p 1, and 60% of sera contained IgE reacting against allergen Euroglyphus maynei （Eur m） 2. IgE against cat allergen, Felisdomesticus （Fel d） 1, was seen in 20%. Only 2% showed specific IgE-reactivity to Der p 10, a panallergen belonging to the tropomyosin family. Serum IgE-reactivity towards other allergens was in general low. IgE-reactivity against pollen allergens showed geographic differences. Conclusions This study clearly confirms that group 1 and group 2 are major allergens of house dust mites. These selected house-dust mite allergy patients are close to being mono-sensitized. Der p 10 is not an important allergen for cross-reactivity. Specific IgE-sensitization towards pollen allergens is low in southern China compared to other regions. The prevalence of food and stinging insect allergens known to give rise to IgE-mediated cross-reactivity is 2% or less.

Incidence and prevention of venous thromboembolism in acutely ill hospitalized elderly Chinese

Background As the third most frequent cardiovascular disease, venous thromboembolism （VTE） remains a major cause of morbidity and mortality in hospitalized patients. The aim of this study was to determine the incidence of VTE and steps for its prevention in acutely ill hospitalized elderly Chinese patients.Methods A prospective multi-center study was conducted from June 2006 to November 2007. A total of 607 patientsfrom 40 research centers in China were enrolled. Data of the patients＇ baseline characteristics, VTE events and prophylaxis/therapy methods were collected.Results Fifty-nine patients （9.7%） had an objectively confirmed VTE during the 90-day follow-up, of which, 59.3%occurred during the first week and 75% within 14 days. Forty-one patients died （6.6%） during the follow-up, 36.6% died within three weeks. We also found that medical disorders including respiratory failure （16.4%）, acute brain infarction （15.6%）, acute infectious diseases （14.3%）, acute coronary artery syndrome （8.7%） and heart failure （7.6%） play a role in provoking VTE. Only 13.0% of the elderly patients with high risk of VTE used low dose unfractionated heparin, 7.1% used low molecular weight heparin, 5.4% used warfarin,0.3% used graduated compression stockings and none of them used intermittent pneumatic compression.Conclusions Our study showed similar results between our study and western countries in the VTE incidence by day 90 in elderly hospitalized patients with acute medical illness. Great caution must be applied in the care of acutely ill elderly hospitalized patients to deal with the complications of VTE. Application of safe and effective prophylaxes against embolism remains a critical challenge.

Evaluation of the efficacy and safety of tiotropium bromide （5 μg） inhaled via Respimat in Chinese patients with chronic obstructive pulmonary disease

Background A pharmacokinetic study in an Asian population showed that tiotropium 5 μg via Respimat leads to the same plasma levels compared to 18 μg via HandiHaler.The objective of the trial was to compare the efficacy and safety of longterm treatment （1 year） with tiotropium bromide （5 μg） via Respimat（R） with placebo in patients with chronic obstructive pulmonary disease （COPD）.Methods A total of 3991 patients were randomized in this double-blind,placebo controlled,parallel group study,while in China 338 patients （309 males,29 females） received either tiotropium bromide （n=167） or placebo （n=171）.Tiotropium bromide solution or matching placebo was delivered via Respimat（R） at a dosage of 5 μg （2 x 2.5 μg/puff） once daily for 48 weeks.Co-primary endpoints were trough forced expiratory volume in one second （FEV1） and the time to first exacerbation.Results Statistically significant improvements in trough FEV1 and trough forced vital capacity （FVC） in the tiotropium group were achieved at weeks 4,24,and 48 compared with those in the placebo group.A statistically significant difference （P=0.0027） in favour of tiotropium was also observed for the time to first exacerbation.The total numbers of exacerbations during treatment were 90 and 128 in the tiotropium and placebo groups,respectively,with a rate ratio of 0.69 （P=0.0164）.The difference between the treatment groups in the adjusted mean changes from baseline of St.George Respiratory Questionnaire （SGRQ） total score was-3.9 （95% Cl：-7.5,-0.2） and was of statistical significance （P=0.0367）.The incidences of serious adverse events （SAEs） in the tiotropium and placebo groups were 16.2% and 17.0%,respectively.Seven deaths occurred whilst patients were on treatment,four in the tiotropium group and three in the placebo group,all of which were assessed as non-related study drugs by the investigators.Conclusions Tiotropium significantly improved lung function and quality of life,delayed the time to first exacerbation,reduced the number of exacerbations.Overall,tiotropium was well tolerated.

DNA vaccine encoding Der p2 allergen down-regulates STAT6 expression in mouse model of allergen-induced allergic airway inflammation

Background Activation of signal transducer and activator of transcription 6 （STAT6） plays a critical role in the late phase of Th2-dependent allergy induction. STAT6 is essential to Th2 cell differentiation, recruitment, and effector function. Our previous study confirmed that DNA vaccination inhibited STAT6 expression of spleen cells induced by allergen. In the present study, we determined whether DNA vaccine encoding Dermatophagoides pteronyssinus group 2 （Der p2 ） could down-regulate the expression and activation of STAT6 in lung tissue from asthmatic mice. Methods After DNA vaccine immunization, BALB/c mice were sensitized by intmperitoneal injection and challenged by intranasal instillation of rDer p2. The levels of the cytokines IL-4 and IL-13 in BAL fluid were measured by enzyme-linked immunosorbent assay. The lung tissue was assessed by immunohistochemical staining with anti-STAT6. The protein expression of STAT6 was determined by Western blot. The activation of STAT6 binding ability was analyzed with electrophoretic mobility shift assay. Results DNA vaccine encoding Der p2 allergen effectively decreased the levels of IL-4 and IL-13 in the asthmatic mice. Histological evidence and Western blot showed that the expression of STAT6 in the DNA treated mice was markedly attenuated. STAT6 binding to specific DNA motif in lung tissue from the gene vaccinated mice was inhibited. Condusion DNA vaccine encoding Der p2 prevents allergic pulmonary inflammation probably by inhibiting the STAT6 signaling pathway in mice with Der p2 allergen-induced allergic airway infammafion.

Prevalence of sensitivity to cockroach allergens and IgE crossreactivity between cockroach and house dust mite allergens in Chinese patients with allergic rhinitis and asthma

Background Cockroaches are an important indoor allergen source causing allergic rhinitis and asthma. The aim of this study was to investigate the cockroach prevalence in mainland of China and the cross-reactivity of IgE between cockroach and house dust mite allergen in Chinese patients.Methods The cockroach sensitization pattern was based on a skin prick test （SPT） obtained from a national multicenter prevalence study, in which 6304 patients from 25 allergy centers across China participated. Factors, including different regions of China, age, gender and the correlations between the American and German cockroaches and house dust mite Der p were investigated. Eighteen out of 1236 clinical sera from south China were selected to perform the cross-inhibition assay between house dust mites and cockroaches.Results Totally 25.7% of patients were SPT positive to the American cockroach （Periplaneta Americana, Per a） and 18.7% SPT positive to the German cockroach （Blattella germanica, Bla g）. The prevalence of positive cockroach SPT was higher in southern than in northern China, higher in adults than in children, and higher in males than in females.Patients had relatively low levels of cockroach SPT reactions, mainly class 1 or 2. Of the SPT positive cockroach patients,88% were also SPT positive to house dust mite （Dermatophagoides pteronyssinus, Der p）. An IgE cross-inhibition study confirmed that Der P sensitization could cause false positive SPT reactions against cockroach.Conclusions A relatively high prevalence of cockroach sensitivity was found in mainland of China. However, a cross-inhibition study showed that only a small number of patients appear to have Bla g and/or Per a as primary sensitizing source. The importance of cockroaches as a risk factor for sensitization and triggers of allergic symptoms in mainland of China needs to be further investigated.

A Potential Chinese Medicine Granule Suppressing ARDS of COVID-19: Keguan-1

Recently,a well-designed,exploratory clinical trial on the management of patients with coronavirus disease 2019(COVID-19)by a Chinese medicine(CM)Keguan-1 has been conducted by Dr.XIAO Xiao-he and his colleagues.(1)For the emergency of COVID-19 treatment,conventional new vaccine and new drug development is a money consuming and time demanding process.

Indoor mite allergen levels, specific IgE prevalence and IgE cross-inhibition pattern among asthmatic children in Haikou, southern China

Background Haikou locates in tropical island with unique mite allergens levels in Haikou, and to investigate the prevalence of between house dust mites. propagation. The aim of this stuy is to determine mite mite specific IgE-sensitization and IgE cross-reactivity Methods Allergen and antigen concentrations against six mite species were tested by enzyme-linked immunosorbent assay （ELISA）. Specific IgE concentrations and cross-inhibitions were measured with ADVIA Centaur . Results Allergen or antigen Dermatophagoides pteronyssinus （Der p 1 ）, Blomia tropicalis （BIot ） and Tyrophagus putrescentia （Tyr p） were detected in dust samples. Dermatophagoides farinae （Der f 1 ）, Lepidoglyphus destructor （Lep d 2）, and Acarus siro （Aca s ） were found in very few samples. Specific IgE tests showed high prevalence of sensitizations against all tested mites with high IgE levels to Der p, Der f, and BIot. Storage mites, BIo t, Tyr p, Lep d, and Aca s, could inhibit Der p from 0 to 50%. Storage mites could inhibit Der f between 30% and 100%. Der p IgE could be inhibited by Der f with up to 90%, and vice versa. Der p could inhibit BIot from 40% to 80%. BIot was able to fully inhibit IgE binding to Lep d, Tyr p, and Aca s compared to partial inhibition by Der p. Conclusions Der p is the dominating mite and has the highest specific IgE prevalence among asthmatic children. BIot represents an important source of storage mite sensitization and some patients may be independently sensitized to both Der p and BIot. High prevalence of sensitization to Der f may be due to IgE-mediated cross-reactivity with Der p and BIo t.

Using optical coherence tomography to detect peripheral pulmonary thrombi

Background Optical coherence tomography （OCT） is a new imaging technique capable of obtaining high-resolution intravascular images of small vessels and has been widely used in interventional cardiology. However, application of OCT in peripheral pulmonary arteries in patients has been seldom documented. Methods Three patients who were highly suspected peripheral pulmonary arteries thrombi and had undergone CT pulmonary angiography but tested negative for thrombi in peripheral pulmonary arteries were enrolled. Subsequently, OCT imaging was performed in peripheral pulmonary arteries. The patients received more than three-month anticoagulative treatment if thrombi were detected by OCT. Thereafter, OCT re-evaluation of the thrombolized blood vessels detected earlier was performed. The changes of thrombi before and after anticoagulative treatment were compared. Results Three patients underwent OCT imaging of peripheral pulmonary arteries. Thrombi were found in most of imaged vessels in these patients. Red and white thrombi can be differentiated, according to features of the thrombus on OCT images. After anticoagulation treatment, these patients＇ symptoms and hypoxemia improved. Repeated OCT imaging showed that most thrombi disappeared or became smaller. Conclusion OCT may be used as a potential tool for detecting peripheral pulmonary artery thrombi and differentiating red thrombi from white ones.

Comparison of effectiveness of whole viral,N and N199 proteins by ELISA for the rapid diagnosis of severe acute respiratory syndrome coronavirus

Background Although severe acute respiratory syndrome （SARS） has been controlled, the subsequently emerging sporadic cases in 2004 emphasize the necessity of developing a rapid diagnostic method, which would be of great help in clinical diagosis and also wild host screening. This study aims to establish an effective and rapid serological tool for the diagnosis of SARS-CoV by comparison among whole viral, N and N199 proteins by ELISA. Methods SARS-CoV N and N199 （a truncated nucleocapsid gene） genes were cloned, expressed, identified by Western blotting, and applied in screening of human and swine samples. Sera of SARS convalescent-phase patients, normal human sera, sera of patients with other respiratory diseases, and swine sera were screened by ELISA, with whole SARS-CoV F69, N and N199 proteins as antigens. Results The sensitivity and specificity of N and N199 proteins in human sera diagnosis were approximate （P=-0.743）, which was higher than whole viral protein but the difference was not significant （P=-0.234）. The N199 protein proved to be more specific in swine sera screening than whole viral and N protein （P〈0.001）. Conclusion N199 protein is feasible in both clinical diagnosis and SARS-CoV reservoir screening.

Pathogenesis of severe acute respiratory syndrome

Severe acute respiratory syndrome （SARS） first emerged in Guangdong province, China in November 2002. During the following 3 months, it spread rapidly across the world, resulting in approximately 800 deaths. In 2004, subsequent sporadic cases emerged in Singapore and China. A novel coronavirus, SARS-CoV, was identified as the etiological agent of SARS.1＇2 This virus belongs to a family of large, positive, single-stranded RNA viruses. Nevertheless, genomic characterization shows that the SARS-CoV is only moderately related to other known coronaviruses.3 In contrast with previously described coronaviruses, SARS-CoV infection typically causes severe symptoms related to the lower respiratory tract. The SARS-CoV genome includes 14 putative open reading frames encoding 28 potential proteins, and the functions of many of these proteins are not known.4 A number of complete and partial autopsies of SARS patients have been reported since the first outbreak in 2003. The predominant pathological finding in these cases was diffuse alveolar damage （DAD）, This severe pulmonary injury of SARS patients is caused both by5 direct viral effects and immunopathogenetic factors, Many important aspects of the pathogenesis of SARS have not yet been fully clarified. In this article, we summarize the most important mechanisms involved in the complex pathogenesis of SARS, including clinical characters, host and receptors, immune system response and genetic factors.

A retrospective serological study of severe acute respiratory syndrome cases in Guangdong province,China

Severe acute respiratory syndrome （SARS） is a life threatening, upper respiratory disease. Its cause is a coronavirus, SARS-CoV. Since its emergence in 2003 in China, SARS has affected more than 8000 patients and caused 776 deaths in 26 countries. A reemergence of SARS occurred in Guangdong province, in which the first case was confirmed on January 5, 2004 and three more reported the following month.

Natural ingredients from Chinese materia medica for pulmonary hypertension

Pulmonary hypertension(PH)is a severe pathophysiological condition characterized by pulmonary artery remodeling and continuous increases in pulmonary artery pressure,which may eventually develop to right heart failure and death.Although newly discovered and incredible treatment strategies in recent years have improved the prognosis of PH,limited types of effective and economical drugs for PH still makes it as a life-threatening disease.Some drugs from Chinese materia medica(CMM)have been traditionally applied in the treatment of lung diseases.Accumulating evidence suggests active pharmaceutical ingredients(APIs)derived from those medicines brings promising future for the prevention and treatment of PH.In this review,we summarized the pharmacological effects of APIs derived from CMM which are potent in treating PH,so as to provide new thoughts for initial drug discovery and identification of potential therapeutic strategies in alternative medicine for PH.