Nanshan Zhong

Publications (61)191.56 Total impact

• Article: Promising therapeutic effects of sodium tanshinone IIA sulfonate towards pulmonary arterial hypertension in patients.

  Jian Wang, Wenju Lu, Wei Wang, Nuofu Zhang, Hua Wu, Chunli Liu, Xiuqing Chen, Yonghua Chen, Yuqin Chen, Qian Jiang, Lei Xu, Lichun Tian, Pixin Ran, Nanshan Zhong
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  ABSTRACT: Pulmonary hypertension (PH) is a lethal disease with no cure currently available. Sodium Tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA isolated as the major active component from salvia miltiorrhiza, a kind of Chinese herbal medicine. We investigate the efficacy of STS towards treatment of PH patients. Five hospitalized patients were randomly enrolled for this study. These patients were suffering from various types of serious PH without getting sufficient benefits from sildenafil treatment (20 mg tid) for at least three months. The efficacy of STS on PH was evaluated by measuring the pulmonary arterial systolic pressure (PASP), RV size by echocardiography, 6-minute walking distance (6MWD), Borg dyspnea score, and WHO functional class of PH. Patients aged from 17 to 46 (average 33±11) years old, pulmonary arterial systolic pressure (PASP) ranged from 60 to 140 mmHg, RV size ranged from 25 to 39 mm were included in study. At the endpoint of observation for 8 weeks of STS infusion, they obtained reduction of PASP in the range of 14-45 (average 28.6±12.5) mmHg, RV size in the range of 0-10 (average 4.2±1.6). All patients exhibited improved exercise capacity with an increase of 6MWD from 63 to 268 (average 138.4±40.7) meters, significantly reduced Borg dyspnea score from maximum 9 down to 1 or 0, and reduced WHO functional class of PH from III or IV down to II. These results indicate that STS exhibits remarkable beneficiary effects on treating PH patients either alone or in concert with sildenafil.
  Journal of thoracic disease. 04/2013; 5(2):169-72.
• Article: Antiviral activity of Isatis indigotica root-derived clemastanin B against human and avian influenza A and B viruses in vitro.

  Zifeng Yang, Yutao Wang, Zhaoguang Zheng, Suishan Zhao, Jin Zhao, Qing Lin, Chuyuan Li, Quan Zhu, Nanshan Zhong
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  ABSTRACT: Clemastanin B, 7S,8R,8'R-(-)-lariciresinol-4,4'-bis-O-β-D-glucopyranoside, is one of the major lignans extracted from Isatis indigotica root (IIR). In this study, the anti-influenza activities of clemastanin B were evaluated in vitro. Clemastanin B was found to inhibit different subtypes of human (H1N1, including swine-origin H1N1; H3N2 and influenza B) and avian influenza viruses (H6N2, H7N3, H9N2) at different magnitudes of activity (IC50 0.087-0.72 mg/ml) while this compound was inactive against respiratory syncytial virus (RSV), adenovirus 3 (ADV3), parainfluenza virus 3 (PIV3), enterovirus 71 (EV71) and human rhinovirus (HRV). An apparent virus titer reduction was detected when MDCK cells were treated with clemastanin B after viral infection, particularly at the early stage, and the ribonucleoprotein (RNP) of the influenza virus was retained in the nucleus after treatment with clemastanin B. These results demonstrated that clemastanin B targets viral endocytosis, uncoating or RNP export from the nucleus. Furthermore, treatment with clemastanin B did not easily result in the emergence of viral drug resistance. The effects of clemastanin B demonstrated in this study may promote the antiviral study of IIR, but additional studies are required to define the anti-influenza mechanism(s).
  International Journal of Molecular Medicine 04/2013; 31(4):867-73. · 1.98 Impact Factor
• Article: BMP4 Increases TRPC Protein Expression by Activating p38MAPK and ERK1/2 Signaling Pathways in PASMC.

  Xiaoyan Li, Wenju Lu, Xin Fu, Yi Zhang, Kai Yang, Nanshan Zhong, Pixin Ran, Jian Wang
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  ABSTRACT: Abnormal bone morphogenetic protein (BMP) signaling has been implicated in the pathogenesis of pulmonary hypertension. We previously found that BMP4 elevated basal intracellular Ca2+ concentration ([Ca2+]i) in distal pulmonary arterial smooth muscle cells (PASMCs) due in large part to enhanced store-operated Ca2+ entry (SOCE) through store-operated Ca2+ channels (SOCC). Moreover, BMP4 upregulated the expression of canonical transient receptor potential (TRPC) proteins thought to compose SOCC. The present study aimed to investigate the signaling pathways through which BMP4 regulates TRPC expression and basal [Ca2+]i in distal PASMCs. Real-time quantitative PCR was used for measurement of mRNA, and western blotting for protein, and fluorescent microscopic for [Ca2+]i to determine the involvement of p38 and ERK1/2 mitogen-activated protein (MAP) kinases signaling in BMP4 induced TRPC expression and elevation of [Ca2+]i in PASMCs. We found that treatment of BMP4 led to activation of both p38MAPK and ERK1/2 in rat distal PASMCs. The induction of TRPC1, TRPC4, TRPC6 expression, and the increases of [Ca2+]i caused by BMP4 in distal PASMCs were inhibited by treatment with either SB203580 (10 M), the selective inhibitor for p38 activation, or the specific p38 siRNA. Similarly, those responses induced by BMP4 were also abolished by treatment of PD98059 (5 M), the selective inhibitor of ERK1/2, or by knockdown of ERK1/2 using its specific siRNA. These results indicate that BMP4 participates in regulation of Ca2+ signaling in PASMCs by modulating TRPC channel expression via activating p38 and ERK1/2 MAP kinases pathways.
  American Journal of Respiratory Cell and Molecular Biology 03/2013; · 5.13 Impact Factor
• Article: Sildenafil Inhibits Hypoxia Induced TRPC Expression in Pulmonary Arterial Smooth Muscle via cGMP-PKG-PPARγ Axis.

  Jian Wang, Kai Yang, Lei Xu, Yi Zhang, Ning Lai, Hua Jiang, Yajie Zhang, Nanshan Zhong, Pixin Ran, Wenju Lu
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  ABSTRACT: Rationale: Transient receptor potential canonical (TRPC) proteins play important roles in chronically hypoxic pulmonary hypertension (CHPH). Previous results indicated sildenafil inhibited TRPC1 and TRPC6 expression in rat distal pulmonary arteries (PA); however, the underlying mechanisms are unknown. Objectives: To investigate the downstream signaling of sildenafil's regulation on TRPC1 and TRPC6 expression in pulmonary arterial smooth muscle cells (PASMCs). Methods: Hypoxia exposed rats (10% O2 for 21 days) and rat distal PASMCs (4% O2 for 60 h) were taken as models to mimic CHPH. Real-time PCR, western blotting, and Fura-2 based fluorescent microscopy were performed for the mRNA, protein, and Ca2+ measurements, respectively. Measurements and Main Results: The cGMP analog CPT-cGMP (100 µM) inhibited TRPC1 and TRPC6 expression, store-operated Ca2+ entry (SOCE), proliferation and migration of PASMCs exposed to prolonged hypoxia. The inhibition of CPT-cGMP on TRPC1 and TRPC6 expression in PASMCs were relieved by either inhibition or knockdown of PKG and PPARγ expression. Under hypoxic condition, CPT-cGMP increased PPARγ expression, the increase was abolished by PKG antagonists Rp8 or KT5823; PPARγ agonist GW1929 significantly decreased TRPC1 and TRPC6 expression in PASMCs. Moreover, hypoxia exposure decreased; whereas, sildenafil treatment increased PKG and PPARγ expression in PASMCs ex vivo, in rat distal PA in vivo. The suppressive effects of sildenafil on TRPC1 and TRPC6 in rat distal PA and on hemodynamic parameters of CHPH were inhibited by treatment with PPARγ antagonist T0070907. Conclusions: Sildenafil inhibits TRPC1 and TRPC6 expression in PASMCs via cGMP-PKG-PPARγ dependent signaling during CHPH.
  American Journal of Respiratory Cell and Molecular Biology 03/2013; · 5.13 Impact Factor
• Article: Detection of mouse cough based on sound monitoring and respiratory airflow waveforms.

  Liyan Chen, Kefang Lai, Joseph Mark Lomask, Bert Jiang, Nanshan Zhong
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  ABSTRACT: Detection for cough in mice has never yielded clearly audible sounds, so there is still a great deal of debates as to whether mice can cough in response to tussive stimuli. Here we introduce an approach for detection of mouse cough based on sound monitoring and airflow signals. 40 Female BALB/c mice were pretreated with normal saline, codeine, capasazepine or desensitized with capsaicin. Single mouse was put in a plethysmograph, exposed to aerosolized 100 µmol/L capsaicin for 3 min, followed by continuous observation for 3 min. Airflow signals of total 6 min were recorded and analyzed to detect coughs. Simultaneously, mouse cough sounds were sensed by a mini-microphone, monitored manually by an operator. When manual and automatic detection coincided, the cough was positively identified. Sound and sound waveforms were also recorded and filtered for further analysis. Body movements were observed by operator. Manual versus automated counts were compared. Seven types of airflow signals were identified by integrating manual and automated monitoring. Observation of mouse movements and analysis of sound waveforms alone did not produce meaningful data. Mouse cough numbers decreased significantly after all above drugs treatment. The Bland-Altman and consistency analysis between automatic and manual counts was 0.968 and 0.956. The study suggests that the mouse is able to present with cough, which could be detected by sound monitoring and respiratory airflow waveform changes.
  PLoS ONE 01/2013; 8(3):e59263. · 4.09 Impact Factor
• Article: A Prospective, Multicenter Survey on Causes of Chronic Cough in China.

  Kefang Lai, Ruchong Chen, Jiangtao Lin, Kewu Huang, Huahao Shen, Lingfei Kong, Xin Zhou, Zhiyang Luo, Lan Yang, Fuqiang Wen, Nanshan Zhong
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  ABSTRACT: ABSTRACT BACKGROUND: The causes of chronic cough in China and its relations with geography, seasonality, age and gender are largely uncertain. METHODS: A prospective, multicenter survey was conducted to evaluate patients with chronic cough across five regions in China by utilizing a modified diagnostic algorithm. The effects of geography, seasonality, age and gender on spectrum of chronic cough were also investigated. RESULTS: The current study evaluated 704 adult patients, including 315 (44.7%) males and 389 (55.3%) females. The causes of chronic cough were determined in 640(90.9%) subjects. Common causes included cough variant asthma(CVA, 32.6%)，upper airway cough syndrome(UACS, 18.6%), eosinophilic bronchitis(EB, 17.2%) and atopic cough (AC, 13.2%). Collectively, these four causes accounted for 75.2% to 87.6% across 5 different regions without significant difference (P>0.05), although there was variation on single causes. Gastroesophageal reflux-related cough (GERC) was identified in 4.6% of causes. Seasonality, gender and age were not associated with the spectrum of chronic cough (all P>0.05). CONCLUSION: CVA, UACS, EB and AC were common causes of chronic cough in China. Geography, seasonality, age and gender were not associated with the spectrum of chronic cough.
  Chest 12/2012; · 5.25 Impact Factor
• Article: Neurogenic airway inflammation induced by repeated intra-esophageal instillation of HCl in guinea pigs : Neurogenic Airway Inflammation Induced by Repeated Intra-esophageal Instillation of HCl in Guinea Pigs.

  Chunli Liu, Ruchong Chen, Wei Luo, Kefang Lai, Nanshan Zhong
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  ABSTRACT: This study was conducted to investigate if repeated intra-esophageal acid administrations may induce neurogenic inflammation in the airways and nodose ganglion in a guinea pig model. Guinea pigs were sedated and perfused with 0.1 N HCl in the distal esophagus via a nasoesophageal catheter for 14 consecutive days. Substance P (SP), neurokinin A (NKA), neurokinin B (NKB), and calcitonin gene-related peptide concentration were measured by ELISA or radioimmunoassay. Neuropeptide expression in the airways and nodose ganglion was detected by immunohistochemistry and assessed semi-quantitatively. Inflammation was found in the trachea and bronchi. There was a threefold increase in substance P concentration in the trachea, main bronchi, and lung homogenate and a twofold increase in NKA and NKB concentration in the main bronchi, lung homogenate, and bronchial alveolus lavage fluid, respectively. The SP and NKA expressions in the airways and nodose ganglion were also significantly increased. Chronic intra-esophageal acid instillation induces significant neurogenic inflammation in the airways and nodose ganglion in the vagus nerve in guinea pigs.
  Inflammation 12/2012; · 1.75 Impact Factor
• Article: Infrared thermal imaging as a novel evaluation method for deep vein thrombosis in lower limbs.

  Fangge Deng, Qing Tang, Yujiang Zheng, Guangqiao Zeng, Nanshan Zhong
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  ABSTRACT: Purpose: Early detection of deep vein thrombosis (DVT) is critical to prevent clinical pulmonary thromboembolism. However, most conventional methods for diagnosing DVT are functionally limited and complicated. The aim of this study was to evaluate the value of infrared-thermal-imaging (IRTI), a novel imaging detection or screening technique, in diagnosis of DVT in animal models.Methods: DVT model of femoral veins was established in nine New Zealand rabbits. The right hind femoral vein was embolized and the contralateral one served as a nonembolized control. Measurements of IRTI, compression ultrasonography (CPUS), and angiography under ultrasonic observation (AGUO) were performed at three time points: T1 (baseline, 10 min prior to surgery), T2 (2 h after thrombin injection), and T3 (48 h postoperatively). Qualitative pseudocolor analysis and quantitative temperature analysis were performed based on mean area temperature (Tav) and mean curvilinear temperature (Tca) of the region of interest as shown in IRTI. Temperature differences (TD) in Tav (TD(Tav)) and Tca (TD(Tca)) between the DVT and control sides were computed. Comparative statistical analysis was carried out by paired t-test and repeated measure, while multiple comparisons were performed by using Greenhouse-Geisser and Bonferroni approach. Values of P < 0.05 and P < 0.01 were considered statistically significant and highly significant.Results: Modeling of DVT was successful in all rabbits, as confirmed by CPUS and AGUO and immediately detected by IRTI. IRTI qualitative analysis of pseudocolor revealed that the bilateral temperatures were apparently asymmetrical and that there were abnormally high temperature zones on the DVT side where thrombosis formed. The results of paired t-test of Tav and Tca between DVT side and control sides did not reveal statistical difference at T1 (Tav: P = 0.817; Tca: P = 0.983) yet showed statistical differences at both T2 (Tav: P = 0.023; Tca: P = 0.021) and T3 (Tav: P = 0.016; Tca: P = 0.028). Results of repeated measure and multiple comparisons of TD(Tav) and TD(Tca) were highly different and significant differences across the T2 (TD(Tav): P = 0.009; TD(Tav): P = 0.03) and T3 (TD(Tav): P = 0.015; TD(Tav): P = 0.021).Conclusions: IRTI temperature quantitative analysis may help further detection of DVT. Additionally, IRTI could serve as a novel detection and screening tool for DVT due to its convenience, rapid response, and high sensitivity.
  Medical Physics 12/2012; 39(12):7224-31. · 2.83 Impact Factor
• Article: House dust mite and storage mite IgE reactivity in allergic patients from Guangzhou, China.

  Chunqing Zhang, Jing Li, Xuxin Lai, Yiwu Zheng, Birgitte Gjesing, Michael D Spangfort, Nanshan Zhong
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  ABSTRACT: In China, house dust mites are important inducers of allergic disease. The importance of allergens from storage mites is less well known. The aim of this study is to access the prevalence of house dust mite and storage mite sensitization and investigate the IgE crossreactivity between house dust mite and storage mite. The skin prick test (SPT) and specific IgE against the mite species D. pteronyssinus, D. farinae, B. tropicalis, Lepidoglyphus destructor, Glycyphagus domesticus, Tyrophagus putrescentiae and Acarus siro were measured. Included were 412 patients with asthma and/or rhinitis for SPT, 244 for specific IgE and 29 sera for IgE inhibition studies. The positive SPT prevalence for D. pteronyssinus was 80.3% and for D. farinae 83.7%. The specific IgE prevalence for D. pteronyssinus was 61.1% and for D. farinae 60.2%. The storage mite species, B. tropicalis and T. putrescentiae had the highest positive SPT prevalence, 66% and 63%, respectively. The specific IgE prevalence was highest for B. tropicalis and G. domesticus, 41% and 37%, respectively. Both SPT and specific IgE levels were much higher for house dust mites compared to storage mites. Inhibition measurements showed that none of the storage mites could fully inhibit the specific IgE against D. pteronyssinus. Only in half of the sera could D. pteronyssinus fully inhibit the IgE against L. destructor and G. domesticus while inhibition of the other storage mites were much lower. Nearly all the specific IgE against storage mites could be inhibited by the other storage mites, though B. tropicalis showed a slightly different pattern from the other storage mites. IgE reactivity against storage mites in Chinese patients is due to both storage mite specific IgE and due to IgE mediated crossreactivity to D. pteronyssinus.
  Asian Pacific journal of allergy and immunology / launched by the Allergy and Immunology Society of Thailand 12/2012; 30(4):294-300. · 0.65 Impact Factor
• Article: A discriminant function model as an alternative method to spirometry for COPD screening in primary care settings in China.

  Jiangyu Cui, Yumin Zhou, Jia Tian, Xinwang Wang, Jingping Zheng, Nanshan Zhong, Pixin Ran
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  ABSTRACT: COPD is often underdiagnosed in a primary care setting where the spirometry is unavailable. This study was aimed to develop a simple, economical and applicable model for COPD screening in those settings. First we established a discriminant function model based on Bayes' Rule by stepwise discriminant analysis, using the data from 243 COPD patients and 112 non-COPD subjects from our COPD survey in urban and rural communities and local primary care settings in Guangdong Province, China. We then used this model to discriminate COPD in additional 150 subjects (50 non-COPD and 100 COPD ones) who had been recruited by the same methods as used to have established the model. All participants completed pre- and post-bronchodilator spirometry and questionnaires. COPD was diagnosed according to the Global Initiative for Chronic Obstructive Lung Disease criteria. The sensitivity and specificity of the discriminant function model was assessed. THE ESTABLISHED DISCRIMINANT FUNCTION MODEL INCLUDED NINE VARIABLES: age, gender, smoking index, body mass index, occupational exposure, living environment, wheezing, cough and dyspnoea. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, accuracy and error rate of the function model to discriminate COPD were 89.00%, 82.00%, 4.94, 0.13, 86.66% and 13.34%, respectively. The accuracy and Kappa value of the function model to predict COPD stages were 70% and 0.61 (95% CI, 0.50 to 0.71). This discriminant function model may be used for COPD screening in primary care settings in China as an alternative option instead of spirometry.
  Journal of thoracic disease. 12/2012; 4(6):594-600.
• Article: Sodium Tanshinone IIA Sulfonate Inhibits Canonical Transient Receptor Potential Expression in Pulmonary Arterial Smooth Muscle from Pulmonary Hypertensive Rats.

  Jian Wang, Qian Jiang, Limei Wan, Kai Yang, Yi Zhang, Yuqin Chen, Elizabeth Wang, Ning Lai, Lei Zhao, Hua Jiang, Yueqian Sun, Nanshan Zhong, Pixin Ran, Wenju Lu
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  ABSTRACT: Danshen, the dried root of Salvia miltiorrhiza, is widely used in clinics in China for treating various diseases including cardiovascular diseases. Sodium Tanshinone IIA sulfonate (STS), a water-soluble derivative of tanshinone IIA isolated as the major active component from Danshen, was recently reported to be effective in attenuating the characteristic pulmonary vascular changes associated with chronically hypoxic pulmonary hypertension (CHPH); however, the underlying detailed mechanisms are poorly understood. In this study, we investigated the effects of STS on basal intracellular Ca2+ concentration ([Ca2+]i) and store-operated Ca2+ entry (SOCE) in distal pulmonary arterial smooth muscle cells (PASMCs) exposed to prolonged hypoxia or isolated from CHPH rats. SOCE measured by Mn2+ quenching of Fura-2 fluorescence in PASMCs from rats exposed to chronic hypoxia (10% O2, 21 days) was increased by 59%, and basal [Ca2+]i by 119% which was inhibited by intraperitoneal injection of STS. These inhibitory effects of STS on hypoxic increases of SOCE and basal [Ca2+]i were associated with reduced expression of TRPC1 and TRPC6 in distal pulmonary arterial smooth muscle, and decreases on right ventricular pressure, right ventricular hypertrophy, and peripheral pulmonary vessel thickening. In ex vivo cultured distal PASMCs from normoxic rats, STS (0~25 µM) dose-dependently inhibited hypoxia-induced cell proliferation and migration, paralleled with attenuation in increases of basal [Ca2+]i, SOCE, mRNA and protein expression of TRPC1 and TRPC6 expression. STS also relieved RVSP, RV hypertrophy, and TRPC1 and TRPC6 protein expression in distal PA as well in MCT-induced rat PAH model. These results indicate that STS prevents PAH development likely by inhibiting TRPC1 and TRPC6 expression, resulting in normalized basal [Ca2+]i, and attenuated proliferation and migration in PASMCs.
  American Journal of Respiratory Cell and Molecular Biology 10/2012; · 5.13 Impact Factor
• Article: Leukotriene D(4) and methacholine bronchial provocation tests for identifying leukotriene-responsiveness subtypes.

  Weijie Guan, Jinping Zheng, Yi Gao, Caiyu Jiang, Yanqing Xie, Jiaying An, Xinxin Yu, Wenting Liu, Nanshan Zhong
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  ABSTRACT: BACKGROUND: Both leukotriene D(4) (LTD(4)) and methacholine bronchial provocation tests are measurements of airway responsiveness; however, their correlation and distinction remain unexplored. OBJECTIVES: We sought to compare the 2 tests and classify leukotriene-responsiveness subtypes in asthmatic patients. METHODS: In this randomized cross-over study we enrolled healthy subjects and asthmatic patients with different control statuses. All subjects underwent both tests with a 2- to 14-day interval. Distribution and correlation of cumulative doses inducing a 20% decrease in FEV(1), LTD(4)/methacholine potency ratio, diagnostic value, and adverse events were recorded and analyzed. Asthmatic patients with a lower cumulative dose for LTD(4) and a higher leukotriene/methacholine potency ratio than geometric means were regarded as leukotriene responsive. RESULTS: Twenty patients with uncontrolled, 22 with partly controlled, and 20 with controlled asthma and 21 healthy subjects were enrolled. Geometric means of cumulative doses for LTD(4) and methacholine (0.272 nmol vs 0.945 μmol) were lowest in patients with uncontrolled asthma, followed by those with partly controlled (0.387 nmol vs 1.933 μmol) and controlled (1.484 nmol vs 3.946 μmol) asthma. The average potency ratio was highest in those with partly controlled asthma (5000.2), followed by those with uncontrolled (3477.7) and controlled (2702.6) asthma. Eighteen leukotriene-responsive asthmatic patients (29.03%) with a cumulative dose of LTD(4) of 0.533 nmol or less and a potency ratio of 3647 or greater were identified. Adverse events, including tachypnea and chest tightness, were similar and mild. No serious adverse event was reported. CONCLUSION: Diagnostic value and safety were ideal in both tests. The combination of cumulative dose for LTD(4) and potency ratio might be useful to identify leukotriene-responsive asthmatic patients.
  The Journal of allergy and clinical immunology 10/2012; · 9.17 Impact Factor
• Article: Specific IgG4 Production during House Dust Mite Immunotherapy among Age, Gender and Allergic Disease Populations.

  Xuxin Lai, Jing Li, Xiaoxiong Xiao, Enmei Liu, Chunqing Zhang, Hongyu Wang, Birgitte Gjesing, Nanshan Zhong, Michael D Spangfort
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  ABSTRACT: Background: Specific IgG4 induced by allergen-specific immunotherapy (SIT) is an immunological marker related to the appearance of clinical tolerance. But specific IgG4 levels in different age, gender and allergic disease populations have not been fully investigated. Methods: This study involved 226 children and 109 adults with allergic rhinitis and/or asthma receiving a 156-week course of Dermatophagoides pteronyssinus (Der p) subcutaneous SIT. Symptom and medication scores, forced expiratory volume after 1 s (FEV(1)) and Der p-specific IgG4 levels at weeks 0, 5, 10, 25, 52, 104 and 156 were analyzed. Results: Rhinitis symptom and medication scores and FEV(1) % predicted in children showed significantly greater improvement than in adults at week 104 and 156 (p < 0.05). Levels of Der p-specific IgG4 showed a significant increase after 10 weeks of subcutaneous SIT (p < 0.0001) and continued to increase during the 156-week SIT period. Before SIT, the initial Der p-specific IgG4 level was higher in children than adults (p = 0.0004). The increase ratio of Der p-specific IgG4 was higher in children than adults at 52 weeks (p < 0.001) and 104 weeks (p = 0.0156) of SIT, and was higher in rhinitis compared to asthma patients at 156 weeks of SIT (p = 0.0244). There was no difference between males and females at any time points. Conclusion: Children are more responsive to SIT, demonstrating clinical and FEV(1) improvement and producing higher levels of allergen-specific IgG4 during a shorter SIT period compared to adults. Rhinitis patients show a higher increase in specific IgG4 compared to patients with asthma symptoms. The increase of Der p-specific IgG4 reflects a specific response of the immune system towards the SIT vaccine being administrated.
  International Archives of Allergy and Immunology 08/2012; 160(1):37-46. · 2.40 Impact Factor
• Article: Non-smoking-related chronic obstructive pulmonary disease: a neglected entity?

  Guangqiao Zeng, Baoqing Sun, Nanshan Zhong
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  ABSTRACT: Chronic obstructive pulmonary disease (COPD) is an increasing cause of morbidity and mortality worldwide, and it has been strongly correlated to tobacco smoking. While a number of studies have concentrated on smokers only, recent published data demonstrate that at least one fourth of patients with COPD are non-smokers, and that the burden of COPD in non-smokers is also higher than previously believed. Risk factors of COPD in non-smokers may include genetic factors, long-standing asthma, outdoor air pollution (from traffic and other sources), environmental smoke exposure (ETS), biomass smoke, occupational exposure, diet, recurrent respiratory infection in early childhood, tuberculosis and so on. In Asian region, indoor/outdoor air pollution and poor socioeconomic status may play important roles in the pathogenesis of non-smoking-related COPD. The prevalence of COPD among never smokers varies widely across nations. Such a variation may arise from several aspects, including study design, definition of COPD, diagnostic criteria, age and gender distribution of the studied population, local risk factors and socioeconomic status. More investigations and efforts are required to elucidate the involved factors and their shared contributions to non-smoking-related COPD so as to achieve better estimation and reduction of the burden of this neglected entity worldwide.
  Respirology 08/2012; 17(6):908-12. · 2.42 Impact Factor
• Article: Diagnosis and treatment of chronic cough in China: an insight into the status quo.

  Kefang Lai, Wei Luo, Guangqiao Zeng, Nanshan Zhong
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  ABSTRACT: Chronic cough is a very common complaint in clinics throughout China. Clinical and basic science research on chronic cough started late, but in recent years the effort has yielded promising findings regarding the etiological diagnosis, treatment and pathogenesis. We found that inflammation in nonasthmatic eosinophilic bronchitis has some similarities to cough variant asthma but also a number of distinct differences. Recent evidence has also suggested a mechanistic link between airway neurogenic inflammation and and gastroesophageal reflux cough (GERC). Cough-related animal models have been developed, including models for esophageal reflux, nonasthmatic eosinophilic bronchitis and allergic rhinitis. Normal reference values for differential cell counts in induced sputum, cough sensitivity and esophageal 24-h pH monitoring in Chinese healthy subjects have been established. By using a modified algorithm for the etiological diagnosis of chronic cough, the causes of chronic cough have been investigated across a number of cities in China. The most common causes of chronic cough are cough variant asthma, eosinophilic bronchitis, upper airway cough symptoms, atopic cough and GERC, however, there are some regional variations. The Chinese National Guidelines on Diagnosis and Management of Chronic Cough were drafted in 2005, updated in 2009, and have been widely publicized and disseminated through many channels since their publication.
  Cough 07/2012; 8(1):4. · 1.26 Impact Factor
• Article: Efficacy and safety of budesonide/formoterol via a dry powder inhaler in Chinese patients with chronic obstructive pulmonary disease

  Nanshan Zhong, Jinping Zheng, Fuqiang Wen, Lan Yang, Ping Chen, Qingyu Xiu, Wanzhen Yao, Tieying Sun, Ziwen Zhao, Huahao Shen, Yi Shi, Jiangtao Lin, Qiang Li
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  ABSTRACT: Objective: To evaluate the efficacy and safety of budesonide (BUD)/formoterol (FORM) compared with BUD, both administered by way of a dry powder inhaler (Turbuhaler*). *Turbuhaler is a registered trade name of AstraZeneca, Södertälje, Sweden.
  01/2012; 28(2):257-265.
• Article: In vitro inhibition of influenza virus infection by a crude extract from Isatis indigotica root resulting in the prevention of viral attachment.

  Zifeng Yang, Yutao Wang, Shan Zhong, Suishan Zhao, Xiangteng Zeng, Ziyao Mo, Sheng Qin, Wenda Guan, Chuyuan Li, Nanshan Zhong
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  ABSTRACT: Isatis indigotica root (IIR) has been widely used as a Chinese medicinal herb to treat regular seasonal influenza over the long history of traditional Chinese medicinal practice. However, its inhibitory activities against influenza virus infections along with the associated mechanisms have not been investigated comprehensively. In this study, the chemical nature, mode of action and in vitro anti-influenza activities of a crude extract (G2) of IIR were characterized. The extract was found to inhibit different subtypes of human or avian influenza viruses at various magnitudes of activity (IC50 0.39‑4.3 mg/ml) in vitro, including A/PR/8/34 (H1N1), A/FM/1/47 (H1N1), A/Aichi/2/68 (H3N2), seasonal influenza (A/Guangzhou/GIRD/02/09 H1N1, B/Guangzhou/GIRD/08/09), novel swine-originating influenza (A/Guangzhou/GIRD/07/09, H1N1), A/Duck/Guangdong/09 (H6N2), A/Duck/Guangdong/94 (H7N3) and A/Chicken/Guangdong/96 (H9N2), while G2 was inactive against respiratory syncytial virus (RSV), adenovirus 3 (ADV3), parainfluenza virus 3 (PIV3) and enterovirus 71 (EV71). An apparent virus titer reduction was detected when the influenza viruses were pretreated with G2, and it was also shown that G2 exhibited inhibitory effects on influenza virus hemagglutination. In addition, G2 played a role in the early stages of infection, which did not easily result in the emergence of virus drug resistance. Thus, G2 may affect the attachment of influenza virus by interfering with the viral particles, thereby preventing the binding of influenza virus to the host cell surface.
  Molecular Medicine Reports 12/2011; 5(3):793-9. · 0.42 Impact Factor
• Article: Translational medicine: what is in a name from the perspective of Chinese clinicians?

  Guangqiao Zeng, Nanshan Zhong
  Science China. Life sciences 12/2011; 54(12):1077-80. · 2.02 Impact Factor
• Article: Efficacy and safety of budesonide/formoterol via a dry powder inhaler in Chinese patients with chronic obstructive pulmonary disease.

  Nanshan Zhong, Jinping Zheng, Fuqiang Wen, Lan Yang, Ping Chen, Qingyu Xiu, Wanzhen Yao, Tieying Sun, Ziwen Zhao, Huahao Shen, Yi Shi, Jiangtao Lin, Qiang Li
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  ABSTRACT: To evaluate the efficacy and safety of budesonide (BUD)/formoterol (FORM) compared with BUD, both administered by way of a dry powder inhaler (Turbuhaler * ). * Turbuhaler is a registered trade name of AstraZeneca, Södertälje, Sweden. This was a 6-month, multicenter, randomized, parallel-group, double-blind, double-dummy design study (NCT 00421122). Patients were randomized to either BUD/FORM 160/4.5 μg, two inhalations twice daily, or BUD 200 μg, two inhalations twice daily. Improvement of lung function, daily symptoms, reliever use and health-related quality-of-life (St George's Respiratory Questionnaire [SGRQ] score) were compared between the two treatment groups. A total of 308 patients with moderate to very severe COPD from 12 centers in China were randomized to BUD/FORM (n = 156) or BUD (n = 152). The primary endpoint, 1-hour post-dose forced expiratory volume in 1 second (FEV1), in the BUD/FORM group improved by 0.18 L (from 0.83 L at baseline to 1.01 L) and this was significantly better (p < 0.001) than the small increase (0.03 L) observed in the BUD group after 24 weeks' treatment. Increases in pre-dose and 15-min post-dose FEV(1) together with 1-hour post-dose forced vital capacity were also significantly larger with BUD/FORM than BUD (p < 0.001 for all). Compared with BUD alone, BUD/FORM improved COPD total symptom scores (-1.04 ± 0.16 vs. -0.55 ± 0.17; p = 0.03), reduced reliever use (-0.85 ± 0.16 puffs/day vs. -0.31 ± 0.16 puffs/day; p = 0.012) and improved health-related quality-of-life (mean change of total SGRQ score -4.5 points (p = 0.0182). Overall, both treatments were well tolerated. In Chinese patients with moderate to very severe COPD, fixed combination treatment with BUD/FORM resulted in clinically meaningful improvements in lung function, health-related quality-of-life, COPD symptoms and a reduction in reliever use, compared with BUD alone and both treatments were well tolerated. Treatment of BUD/FORM for milder patients with COPD and head to head comparison of Chinese and Caucasians in future studies will be helpful to expand upon the findings of the current clinical trial.
  Current Medical Research and Opinion 11/2011; 28(2):257-65. · 2.38 Impact Factor
• Article: Outdoor air pollution and respiratory health in Asia.

  Kian Fan Chung, Junfeng Zhang, Nanshan Zhong
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  ABSTRACT: With the rapid economic development occurring in the last decade in many countries of Asia, the level of air pollution has increased from both industrial and motor vehicle emissions. Compared with Europe and North America, the potential health effects of this increasing air pollution in Asia remain largely unmeasured. Recent data published by the Health Effects Institute from some major cities in India and China reveal that a 10 µg/m(3) increase in PM(10) was associated with an increase in mortality of 0.6% in daily all-natural cause mortality, with higher risks being found at extremes of high temperatures and in the lowest economically advantaged population. Other Asian studies have confirmed the link between hospital admissions for the worsening of COPD and the increase in asthma prevalence to levels of outdoor air pollutants. Although potential health effects appear to be similar to already-published Western data, it is important that further studies be carried out in Asia that will inform the public and the authorities of the necessity to curb levels of outdoor air pollutants to acceptable levels.
  Respirology 08/2011; 16(7):1023-6. · 2.42 Impact Factor