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To explore the whole-body metabolic tumour volume (WBMTV), whole-body total lesion glycolysis (WBTLG) and tumour whole-body maximum standardised uptake value (WBSUVmax) of post-treatment 18F-fluorodeoxyglucose PET/computed tomography (18F-FDG PET/CT) in predicting the overall survival (OS) in patients with cervical squamous cell carcinoma (SCC).The clinical data of 74 patients with cervical SCC who received 18F-FDG PET/CT were retrospectively analysed. WBMTV, WBTLG and WBSUVmax, as well as the serum SCC-Ag level, were measured. The Kaplan-Meier method and Cox regression were used to analyse the relationships of PET/CT parameters with OS.The risk of death was 13.942-fold greater in the PET-positive group than in the PET-negative group (P 0.001). In the PET-positive group, univariate analysis showed that OS was significantly correlated with WBMTV and WBTLG; it was not correlated with WBSUVmax, SCC-Ag, age, pathological stage or treatment after PET (P 0.05). Patients with positive PET findings were divided into two groups according to the median of WBMTV or WBTLG; there was a significant difference in OS between the two groups. The risk of death in patients with positive PET imaging findings and high SCC-Ag level was 18.356-fold greater than in patients with negative PET imaging findings (P 0.001).WBMTV and WBTLG have important prognostic value in the prediction of OS in post-treatment patients with cervical SCC. OS was significantly decreased in patients who had both positive PET imaging findings and high SCC-Ag level.

Background Mental disorders impose heavy burdens on patients’ families and children. It is imperative to provide family-focused services to avoid adverse effects from mental disorders on patients’ families and children. However, implementing such services requires a great deal of involvement of mental health workers. This study investigated the attitudes, knowledge, skills, and practices in respect to family-focused practices (FFP) in a sample of Chinese mental health workers. Methods A cross-sectional study design was employed to examine the attitudes, knowledge, skills, and practices of a convenience sample of Chinese mental health workers in respect to FFP, using the Chinese version of the Family-Focused Mental Health Practice Questionnaire (FFMHPQ). Results In total, 515 mental health workers participated in our study, including 213 psychiatrists, 269 psychiatric nurses, and 34 allied mental health professionals (20 clinical psychologists, 9 mental health social workers, and 4 occupational therapists). Compared with psychiatric nurses, psychiatrists and allied mental health professionals provided more support for families and children of patients with mental illness and were more willing to receive further training in FFP. However, there were no significant differences on knowledge, skills, and confidence across different profession types. After adjusting for demographic and occupational variables, previous training in FFP was positively associated with mental health workers’ knowledge, skills, and confidence about FFP, but not actual support to families and children. Conclusions Professional differences on FFP exist in Chinese mental health workers. Training is needed to engage psychiatrists and other allied workforce in dissemination and implementation of FFP in China.

Background Although the experiences of mothers with mental illness are well researched in Western countries, little is known about the experiences of Chinese mothers. This study aims to explore the experiences of family life and parenting of Chinese mothers, in the context of their mental illness. Methods Fourteen Chinese mothers with mental illness undertook in-depth, semi-structured interviews. Interpretative Phenomenological Analysis was employed to guide the data analysis. Results Seven themes were identified: motherhood as a central identity, the stigma associated with being a mother with mental illness, participants’ perceptions about the impact of mental illness on parenting and their children, experiences of talking to children about mental illness, how having children impacts mothers’ illness and recovery, and support obtained and needed. Similar to Western mothers, Chinese mothers experienced stigma and fluctuating mental illness symptoms which impacted on parenting. Unlike mothers based in Western countries, the mothers interviewed in this study highlighted complicated co-caring relationships with parents-in-law and did not raise child custody concerns. Conclusions Mental health professionals need to have the skills to identify and recognize the mothering role of their clients. Culturally sensitive interventions are required to assist Chinese families where mothers have a mental illness. Future research is required to investigate family experiences of parental mental illness from the perspectives of children, partners, and mental health professionals.

Purpose The purpose of this study was to investigate the reproducibility of fluid-phase measurements in PBS-treated sputum supernatant, processed using the two-step method, of healthy and stable COPD individuals. Methods Nine healthy subjects and 23 stable COPD patients provided sputum twice within 6 days. A two-step sputum processing method was used to obtain PBS-treated supernatant and sputum cells. Soluble protein markers and IgG and IgM autoantibody profiles in PBS supernatant were analyzed using customized microarrays. Repeatability of measurements was assessed by paired-sample testing and an intraclass correlation coefficient, then graphically reported by Bland-Altman plot. Results There was no significant difference between the repeated detection of 8/10 types of soluble protein markers, all 13 types of IgG autoantibodies, and 12/13 types of corresponding IgM autoantibodies in PBS supernatant. The repeatability of measurements in PBS supernatant was substantial to very good for interleukin 6 (IL6), IL8, IL13, IL10, IL33, vascular endothelial growth factor, soluble receptor for advanced glycation end-products, and tumor necrosis factor-α; for IgG autoantibodies against aggrecan, centromere protein B (CENP-B), collagen II, collagen IV, cytochrome C, elastin, heat shock protein 47 (HSP47), HSP70, and La/Sjogren syndrome type B antigen; for IgM autoantibodies against CENP-B, collagen I, collagen II, collagen IV, cytokeratin 18, and HSP70; and for sputum neutrophils, macrophages and eosinophils count. Bland-Altman plots suggested good consistency within repeated measurements. Stable COPD patients differed from healthy subjects in the proportion of neutrophils and eosinophils; relative fluorescence intensity of anti-cytochrome C IgG, anti-aggrecan IgM, and anti-cytochrome C IgM. There was a significant positive correlation for stable COPD patients between sputum anti-collagen II IgG and post-bronchodilator FEV1%. Conclusion We confirmed fluid-phase measurements in PBS-treated sputum supernatant by high-throughput techniques with good repeatability. We demonstrated the presence of IgG and IgM autoantibodies to multiple antigens in the airways of COPD patients.

Mingshan Xue,1,* Chuanxu Cai,2,* Lili Guan,1,* Yifan Xu,1 Jinsheng Lin,1 Yifeng Zeng,1 Haisheng Hu,1 Rongchang Chen,1 Hongman Wang,3 Luqian Zhou,1 Baoqing Sun1 1Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Department of Laboratory Medicine, Shenzhen Institute of Respiratory Diseases, Shenzhen People’s Hospital, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical Medical College of Jinan University, Shenzhen, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, The Fifth Affiliated Hospital of Zunyi Medical University Zhuhai, Zhuhai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Luqian Zhou; Baoqing Sun Email zhlx09@163.com; sunbaoqing@vip.163.comBackground and Objective: Severe chronic obstructive pulmonary disease (COPD) is the terminal stage of the disease characterized by declined lung function, malnutrition, and poor prognosis. Such patients cannot tolerate long-time sports rehabilitation owing to dyspnea and fail to achieve the desired therapeutic effect; therefore, increasing nutritional support will be an important strategy for them. The present study applied metabolomics technology to evaluate the correlation between serum concentrations of polyunsaturated fatty acid (PUFA) metabolites, nutritional status, and lung function in patients with COPD to provide a theoretical basis for accurate nutritional support.Materials and Methods: We enrolled 82 patients with stable severe COPD in our hospital. The general characteristics including height, weight, and lung function were recorded. Metabolomics was used to detect the concentrations of serum metabolites of n-3 and n-6 at baseline and at 24 and 52 weeks after enrollment. The correlations between nutrition level and pulmonary function and clinical indicators were evaluated.Results: The concentrations of n-3 and n-6 increased over time along with the progression of COPD. Body mass index (BMI) and percent of ideal body weight (IBW%) decreased with disease development, and BMI was found to be significantly correlated with FEV1% predicted and FEV1/FVC. Serum levels of n-6 metabolites such as linoleic acid (LA), γ-linoleic acid (GLA), and arachidonic acid (ARA) (all P < 0.01) and the n-3 metabolites such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (all P < 0.05) showed significant correlations with BMI and were closely correlated with FEV1% predicted and FEV1/FVC of lung function (all P< 0.05).Conclusion: This study demonstrates that malnutrition in patients with severe COPD is progressive and is positively correlated with n-3 and n-6 polyunsaturated fatty acids and lung function.Keywords: chronic obstructive pulmonary disease, metabolomics, nutritional level

Lili Guan,1,* Jiawen Xu,1,* Weiliang Wu,1,* Jianhua Chen,1,* Xiaoying Li,2,* Bingpeng Guo,1 Yuqiong Yang,1 Yating Huo,1 Luqian Zhou,1 Rongchang Chen1 1State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; 2The First Affiliated Hospital, School of Clinical Medicine of Guangdong Pharmaceutical University, Guangzhou, China *These authors contributed equally to this work Purpose: Patients with advanced-stage COPD often experience severe hypoxemia. Treatment with long-term oxygen therapy (LTOT) may relieve patients’ symptoms and increase survival. As COPD is incurable, improving patients’ health-related quality of life is important. The Chinese version of the Severe Respiratory Insufficiency Questionnaire (SRI) is valid for patients with hypercapnic COPD undergoing noninvasive positive airway pressure ventilation at home. However, the reliability and validity of the Chinese SRI for patients with COPD undergoing LTOT have not been investigated. Patients and methods: We analyzed reliability using Cronbach’s α coefficient. Construct validity was assessed with principal, exploratory, and confirmatory factor analysis. Concurrent validity was evaluated through the correlation between SRI domains and Chronic Respiratory Disease Questionnaire (CRQ) domains. Content validity was assessed by calculating the correlation between each SRI item score and the total score for the relevant domain. Results: In total, 161 patients participated in this study. The Cronbach’s α coefficient for all SRI domains was >0.7, except for the attendant symptoms and sleep domain. Exploratory and confirmatory factor analysis showed a good model fit for each domain, but the factors extracted from each domain were correlated. SRI and CRQ domains correlated well with respect to similar aspects of health-related quality of life, indicating good concurrent validity. Content validity was indirectly shown by a good correlation between each item score and the total score of the relevant domain. Conclusion: The Chinese version of the SRI has a good reliability and validity for patients with COPD undergoing LTOT in China. Keywords: severe respiratory insufficiency questionnaire, long-term oxygen therapy, health-related quality of life, chronic obstructive pulmonary disease

In the present work, the protective effect of polysaccharide from Rosa rugosa (RRP) on acute alcoholic liver disease (ALD) was investigated. The viscera index, liver function and H&E staining results showed that RRP had a protective effect on ALD mice. RRP can increase activities of SOD, GSH, GSH-Px and decrease the content of NO, MDA in ALD mice. At the same time, the serum levels of IL-6, IL-1β and TNF-α were decreased in ALD mice treated with RRP. Our results suggested that RRP significantly prevented alcohol-induced hepatotoxicity as the concentration rises. In this study, 16S rRNA sequencing technology was used to explore the effect of RRP on the gut microbiota in ALD mice. It was found that RRP can reduce the pathogenic Gammaproteobacteria and Patescibacteria but increase the beneficial gut Firmicute and Lachnospira, thereby maintain the relative stability of the gut microbiota by adjusting the gut-liver axis. This research not only opens up a new idea for the research on the efficient utilization of resources and physiological activity of Rosa rugosa, but also provides theoretical references for the search and development of natural liver-protecting drugs.

Objective Children of parents with mental illness (COPMI) are vulnerable during the COVID-19 pandemic. The study aimed to assess the psychosocial impacts of the pandemic and identify potential factors influencing their mental health. Method 665 COPMI from six sites including Wuhan in China were enrolled. COPMI's mental health and the impacts of COVID-19 were assessed by an online survey. Univariate and multivariate analyses were performed to examine the association between impact factors and participants’ mental health. Results 16.1 % of participants were in abnormal range of mental health, with interpersonal relationship being the most common problem. 48.6 % of participants reported quite worried about the epidemic. All aspects of adverse effects of COVID-19 were more prevalent among COPMI in Wuhan than in other sites. Concerns about COVID-19 (OR = 1.7, p = 0.02), decreased family income (OR = 2.0, p = 0.02), being physically abused (OR = 2.1, p = 0.04), witnessing family members being physically abused (OR = 2.0, p = 0.03), and needs for promoting family members' mental health (OR = 2.2, p

Weiliang Wu,1,* Lili Guan,1,* Xiaoying Li,2,* Lin Lin,1 Bingpeng Guo,1 Yuqiong Yang,1 Zhenyu Liang,1 Fengyan Wang,1 Luqian Zhou,1 Rongchang Chen1 1Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, 2Department of Respiratory Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China *These authors contributed equally to this work Purpose: To evaluate the compatibility and correlation between noninvasive surface respiratory electromyography and invasive transesophageal diaphragmatic electromyography measurements as facilitating indicators of neural respiratory drive (NRD) evaluation during treadmill exercise.Patients and methods: Transesophageal diaphragmatic electromyogram activity (EMGdi,es) and surface inspiratory electromyogram (EMG) activity, including surface diaphragmatic EMG activity (EMGdi,sur), surface parasternal intercostal muscle EMG activity (EMGpara), and surface sternocleidomastoid EMG activity (EMGsc), were detected simultaneously during increasing exercise capacity in 20 stable patients with COPD. EMGdi,es, EMGdi,sur, EMGpara, and EMGsc were quantified using the root mean square (RMS) and were represented as RMSdi,es, RMSdi,sur, RMSpara, and RMSsc, respectively.Results: There was a significant association between EMGdi,es and EMGdi,sur (r=0.966, p

We conducted a randomised controlled trial to assess the effects of daily breathing pattern changes to stable patients with COPD excluding the confounding factors of inspiratory muscle mobilization, by ensuring the load intensities of two inspiratory training devices were equal.Sixty patients with COPD were randomised to three groups: resistive-IMT group (T-IMT, 21 patients), threshold-IMT (R-IMT, 19 patients), and a control group (20 patients). Inspiratory load intensity for both methods was set at 60% of maximal inspiratory pressure (MIP), a measure of inspiratory muscle strength, which, along with health-related quality of life (HRQoL), degree of dyspnoea, and exercise capacity, were conducted before and after 8 weeks of daily IMT.At 8 weeks, there was no significantly difference of MIP between the R- and T-IMT groups (P 0.05). Chronic Respiratory Disease Questionnaire and Transition Dyspnea Index scores improved significantly after each training program compared with controls (P 0.05), and R-IMT was significant better (P 0.05). R-IMT was better than T-IMT in performance of exercise (P 0.05).In summary, in clinically stable patients with COPD, 8 weeks of R-IMT was superior to 8 weeks of equal-intensity T-IMT in improving HRQoL, degree of dyspnoea, and exercise capacity.

Luqian Zhou,1,* Xiaoying Li,1,* Lili Guan,1,* Jianhua Chen,1 Bingpeng Guo,1 Weiliang Wu,1 Yating Huo,1 Ziqing Zhou,1 Zhenyu Liang,1 Yuqi Zhou,2 Jie Tan,3 Xin Chen,4 Yuanlin Song,5 Rongchang Chen1 1Department of Respiratory Medicine, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, 2Department of Respiratory Medicine, The Third Affiliated Hospital of Sun-Yat Sen University, 3Department of Respiratory Medicine, The First Affiliated Hospital, School of Clinical Medicine of Guangzhou Pharmaceutical University, 4Department of Respiratory Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, 5Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: The benefits of noninvasive positive pressure ventilation (NPPV) in patients with hypercapnic COPD are controversial. It is presumed that methodology and appropriate use of NIV ventilator might be crucial for the outcomes. With the new built-in software, the performance of NIV can be monitored at home, which can guarantee the compliance and appropriate use. This study investigated effects of home use of NIV in hypercapnia in COPD patients using the NIV ventilator with built-in software for monitoring. Methods: The current multicenter prospective, randomized, controlled trial enrolled patients with stable GOLD stages III and IV hypercapnic COPD. Patients were randomly assigned via a computer-generated randomization sequence, with a block size of four patients, to continue optimized treatment (control group) or to receive additional NPPV (intervention group) for 3months. The primary outcome was arterial carbon dioxide pressure (PaCO2). Data were derived from built-in software and analyzed every 4weeks. Analysis was carried out with the intention to treat. This study is registered with ClinicalTrials.gov, number NCT02499718. Results: Patients were recruited from 20 respiratory units in China from October 1, 2015, and recruitment was terminated with a record of the vital statistics on May 31, 2016. A total of 115 patients were randomly assigned to the NPPV group (n=57) or the control group (n=58). Patients complied well with NPPV therapy (mean [± standard deviation] day use 5.6±1.4h). The mean estimation of leaks was 37.99±13.71L/min. The changes in PaCO2 (-10.41±0.97 vs -4.32±0.68mmHg, P=0.03) and 6-min walk distance (6MWD) (38.2% vs 18.2%,P=0.02) were statistically significant in the NPPV group versus the control group. COPD assessment test (CAT) showed a positive trend (P=0.06) in favor of the NPPV group. Pulmonary function and dyspnea were not different between groups. Conclusion: Ventilators equipped with built-in software provided methodology for monitoring NIV use at home, which could facilitate the improvement of compliance and quality control of NIV use. It was shown that three months use of NIV at home could reduce the PaCO2 and improve exercise tolerance (6MWD) in chronic hypercapnic COPD patients. Keywords: COPD, noninvasive positive pressure ventilation, long-term oxygen therapy, chronic respiratory failure, built-in software

Rong-chang Chen,1,* Xiao-ying Li,1,* Li-li Guan,1 Bing-peng Guo,1 Wei-liang Wu,1 Zi-qing Zhou,1 Ya-ting Huo,1 Xin Chen,2 Lu-qian Zhou1 1State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, 2Zhujiang Hospital of Southern Medical University, Guangzhou, People’s Republic of China*These authors contributed equally tothis work Purpose: Patients with COPD often experience skeletal muscle dysfunction. For those who are unable or unwilling to undertake physical training, neuromuscular electrical stimulation (NMES) may provide an alternative method of rehabilitation. The purpose of this meta-analysis was to investigate the controversial topic of whether this therapy is effective in patients with moderate-to-severe COPD. Patients and methods: We pooled data from nine trials published between January 9, 2002 and January 4, 2016 across PubMed, Embase, Cochrane Central Register of Controlled Trials, Google Scholar, and relevant websites for randomized controlled trials. In these trials, patients with moderate-to-severe COPD were randomly allocated to receive NMES. Primary outcomes were quadricep strength and exercise capacity. The secondary outcome was health-related quality of life. Results: We extracted data from 276 patients. NMES contributed to statistically improved quadricep strength (standardized mean difference 1.12, 95% confidence interval [CI] 0.64–1.59, I2=54%; P>0.00001) and exercise capacity, including longer exercise distance (weighted mean difference 51.53, 95% CI 20.13–82.93, I2=90%; P=0.001), and longer exercise endurance (standardized mean difference 1.11, 95% CI 0.14–2.08, I2=85%; P=0.02). There was no significant difference in St George’s Respiratory Questionnaire scores (weighted mean difference -0.07, 95% CI -2.44 to 2.30, I2=56%; P=0.95). Conclusion: NMES appears an effectual means of enhancing quadricep strength and exercise capacity in moderate-to-severe COPD patients. Further research is demanded to clarify its effect on other outcomes and determine the optimal parameters for an NMES program. Keywords: neuromuscular electrical stimulation, chronic obstructive pulmonary disease, quadriceps muscle strength, exercise capacity

It has been demonstrated that microRNAs (miRNAs) act as oncogenes or tumor suppressors in a variety of cancers. Our previous work suggested that miR-10a/b functioned as a tumor suppressor in gastric cancer, and miR-10b was also reported to be significantly downregulated in advanced stage cervical cancer tissues. However, the aberrant expression of miR-10b in cervical cancer and its possible role in cervical carcinogenesis was largely unknown. In this study, we investigated the expression of miR-10b in cervical cancer tissues, carcinoma in situ tissues, mild dysplasia, moderate dysplasia, severe dysplasia tissues, and normal controls. We found that miR-10b was significantly downregulated during cervical cancer progression, and the lower level of miR-10b in cervical cancer was significantly associated with a more aggressive tumor phenotype. Moreover, overexpression of miR-10b in cervical cancer cells could inhibit the cell proliferation and invasion, and the further mechanism study suggested that its role was possibly through directly targeting HOXA1. These results suggested that the downregulation of miR-10b and the resulting elevated HOXA1 level in cervical cancer tissues might play critical roles in cervical cancer progression.

As of 17 February, 2020, China has 70 635 confirmed cases of coronavirus disease 2019 (COVID-19), including 1772 deaths [1]. Human-to-human spread of the virus via respiratory droplets is currently considered to be the main route of transmission. However, exhaled air dispersion during non-invasive respiratory support may increase the risk of coronavirus transmission, and requires more attention from medical personnel and patients., Non-invasive respiratory support plays an essential role in the treatment of COVID-19. More awareness is needed of viral transmission through exhaled air. http://bit.ly/39kNrrF

Background Difference between combined inspiratory and expiratory muscle training in same respiratory cycle or different cycles remained unclarified. We explored the difference between both patterns of combined trainings in patients with COPD. Methods In this randomized, open-label, controlled trial, stable COPD subjects trained for 48 minutes daily, for 8 weeks, using a monitoring device for quality control. Ninety-two subjects were randomly and equally assigned for sham training, inspiratory muscle training(IMT), combined inspiratory and expiratory muscle training in same cycle(CTSC) or combined inspiratory and expiratory muscle training in different cycles(CTDC). Respiratory muscle strength, as the primary endpoint, was measured before and after training. Registry: ClinicalTrials.gov (identifier: NCT02326181). Results Respiratory muscle training improved maximal inspiratory pressure(PImax), while no significant difference was found in PImax among IMT, CTSC and CTDC. Maximal expiratory pressure(PEmax) in CTSC and CTDC was greater than IMT(P = 0.026, and P=0.04, respectively) and sham training (P = 0.001). IMT, CTSC, and CTDC shortened inhalation and prolonged exhalation(P < 0.01). Subjects with respiratory muscle weakness in IMT and CTDC exhibited greater increase in PImax than those without. IMT, CTSC and CTDC showed no difference in symptoms and quality of life scales among themselves(P > 0.05). Conclusion Both patterns of CTSC and CTDC improved inspiratory and expiratory muscle strength, while IMT alone only raised PImax. Respiratory muscle training might change the respiratory cycles, and be more beneficial for COPD patients with inspiratory muscle weakness.

To assess the correlation between surface respiratory electromyography(sEMG) and esophageal diaphragm electromyography(EMGdi) at different levels of neural respiratory drive (NRD).Randomised parallel design controlled trial.The First Affiliated Hospital of Guangzhou Medical University.15 healthy subjects and 1 severe to very severe stable COPD patients were studied.15 healthy subjects performed incremental inspiratory threshold loading (ILT) and 15 stable COPD patients underwent noninvasive positive pressure ventilation (NPPV).The correlation between EMGdi and sEMG at different NRD levels was analyzed. EMGdi was performed with a multi-pair esophageal electrode catheter; sEMG were was performed by surface diaphragm EMG(located in right anterior axillary line and left anterior axillary line respectively expressed as sEMGdi(r) andsEMGdi(l))、surface parasternal EMG(sEMGpara),and surface sternocleidomastoid EMG(sEMGsc).Signals were normalized using the peak EMG expressed as EMG%max.The mean ± standard deviation resting EMGdi%max was higher in patients with COPD than in healthy subjects (57.26%±15.45% vs13.64% ±4.96%, respectively; p 0.001).During ILT and NPPV, EMGdi was correlated with sEMGdi (r), sEMGdi (1), sEMGpara and sEMGsc (r = 0.90, 0.87, 0.90, 0.90 and r = 0.92, 0.83, 0.92 and 0.71, respectively; all P 0.001).A strong relationship is present between NRD measured by EMGdi%max and NRD measured by sEMG%max. sEMG%max serves as a non-invasive marker of NRD.

High-pressure non-invasive positive pressure ventilation (NPPV) is a new strategy targeted at maximally reducing arterial carbon dioxide. However, high inspiratory positive airway pressure (IPAP) might cause respiratory adverse events likely to diminish the benefit of NPPV. In the setting of ventilatory support, monitoring NPPV efficacy and resolving problems promptly are critical. This study assessed the treatment effect of high and low-pressure NPPV in chronic hypercapnic COPD using home ventilator with built-in software. In this pilot study, we investigated 34 patients using NPPV for 3 months. 13 patients used high-pressure ventilation and 21 patients used low-pressure ventilation. The primary outcome was daytime partial pressure of arterial blood carbon dioxide (PaCO2). There were no between-group differences in daytime PaCO2 and FEV1, but a trend favouring high-pressure NPPV was observed. Significant between-group differences were found in the transition dyspnoea index (TDI) (high-pressure, 1.69 ± 1.75, versus low-pressure, −0.04 ± 2.71, p = 0.044). No differences were found in usage time, leakage, health-related quality of life, spirometry, or 6-minute walk test. High-pressure NPPV with built-in software monitoring in patients with chronic hypercapnic COPD is associated with improvement in TDI scores and a positive trend in favour of high-pressure NPPV for improving PaCO2 is observed.

Genipin is the major active component of Gardeniae fructus and has been shown to ameliorate diabetes and insulin resistance in rat models. In this study, we first investigated the effect of genipin on obesity and the related lipid metabolism mechanisms in diet-induced obese rats. Our results showed that genipin reduced body weight, food intake, and visceral fat mass; ameliorated dyslipidemia, glucose intolerance, insulin intolerance, adipocyte hypertrophy, and hepatic steatosis; and reduced serum tumor necrosis factor-α level in diet-induced obese rats. Quantitative real-time reverse-transcription polymerase chain reaction results further illustrated that genipin promoted lipolysis and β-oxidation of fatty acid by upregulating gene expressions of hormone-sensitive lipase and adipose triglyceride lipase in white adipose tissue (WAT) and peroxisome proliferator-activated receptor-α and carnitine palmitoyltransferase 1α in hepatic tissue. Moreover, genipin promoted browning of WAT by upregulating the mRNA and protein levels of uncoupling protein 1 and PRD1-BF1-RIZ1 homologous domain containing 16 in WAT. Additionally, genipin inhibited gene expressions of activin receptor-like kinase 7, tumor necrosis factor-α, and interlukin-6 in WAT. These results indicated that genipin had a potential therapeutic role in obesity, in which regulation of lipid mobilization and browning of WAT were involved.

Weiliang Wu,1 Xianming Zhang,2 Lin Lin,1 Yonger Ou,1 Xiaoying Li,1 Lili Guan,1 Bingpeng Guo,1 Luqian Zhou,1 Rongchang Chen1 1State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 2Department of Respiratory Medicine, The First Affiliated Hospital of Guizhou Medical University, Guizhou, People’s Republic of China Purpose: Inspiratory muscle training (IMT) is a rehabilitation therapy for stable patients with COPD. However, its therapeutic effect remains undefined due to the unclear nature of diaphragmatic mobilization during IMT. Diaphragmatic mobilization, represented by transdiaphragmatic pressure (Pdi), and neural respiratory drive, expressed as the corrected root mean square (RMS) of the diaphragmatic electromyogram (EMGdi), both provide vital information to select the proper IMT device and loads in COPD, therefore contributing to the curative effect of IMT. Pdi and RMS of EMGdi (RMSdi%) were measured and compared during inspiratory resistive training and threshold load training in stable patients with COPD.Patients and methods: Pdi and neural respiratory drive were measured continuously during inspiratory resistive training and threshold load training in 12 stable patients with COPD (forced expiratory volume in 1s ± SD was 26.1%±10.2% predicted).Results: Pdi was significantly higher during high-intensity threshold load training (91.46±17.24cmH2O) than during inspiratory resistive training (27.24±6.13cmH2O) in stable patients with COPD, with P

Objective Green tea polyphenols (GTPs) are now being considered possible protective agents in neurodegenerative diseases such as Alzheimer's disease (AD). Previous studies suggested that GTPs could inhibit amyloid fibril formation and protect neurons from toxicity induced by β-amyloid. However, whether GTPs can ameliorate learning and memory impairments and also reduce tau hyperphosphorylation induced by okadaic acid (OA) in rats remains unclear. The aim of this study was to determine if GTPs have neuroprotection against OA-induced neurotoxicity. Methods In this work, rats were pretreated with GTPs by intragastric administration for 4 wk. Then OA was microinjected into the right dorsal hippocampus. Morris water maze tests were used to test the ethologic changes in all groups, and tau protein hyperphosphorylation was detected both in vivo and in vitro. Results The ethologic test indicated that the staying time and swimming distance in the target quadrant were significantly decreased after OA treatment, whereas rats pretreated with GTPs stayed longer in the target quadrant. Methyl thiazolyl tetrazolium assay and lactate dehydrogenase leakage showed that GTPs greatly ameliorated primary hippocampal neurons damage induced by OA. Furthermore, reduced hyperphosphorylated tau protein was detected with GTPs pretreatment. Conclusion Taken together, our results suggest that GTPs have neuroprotection against OA-induced neurotoxicity.

The dopamine D4 receptor (DRD4) gene has been frequently studied in relation to attention deficit hyperactivity disorder (ADHD) but little is known about the contribution of single nucleotide polymorphisms (SNPs) of the DRD4 gene to the development and persistence of ADHD. In the present study, we examined the association between two SNPs in DRD4 (rs1800955, rs916455) and adult ADHD persistence in a Chinese sample. Subjects (n=193) were diagnosed with ADHD in childhood and reassessed in young adulthood at an affiliated clinic of Peking University Sixth Hospital. Kaplan-Meier survival analyses and Cox proportional hazard models were used to test the association between ADHD remission and alleles of the two SNPs. DRD4 rs916455 C allele carriers were more likely to have persistent ADHD symptoms in adulthood. No significant association was found between rs1800955 allele and the course of ADHD. These newly detected associations between DRD4 polymorphisms and ADHD prognosis in adulthood may help to predict the persistence of childhood ADHD into adulthood.

Melanoma, as one of the most highly metastatic types of cancer, is resistant to current treatment methods, including popular targeted molecular therapy. Consequently, it is essential to develop a deeper understanding of the mechanisms involved in melanoma progression so that alternative treatments may be identified. To date, accumulating evidence supports the use of calpains, including calpain small subunit 1 (also known as Capn4 or CAPNS1), which affect cancer progression through many pathways, such as epithelial‑mesenchymal transition (EMT), the Wnt/β-catenin (β-catenin) and the nuclear factor κB (NF-κB) signaling pathways. The EMT pathway is well known as one of the most important events in tumor metastasis. The present study observed cross-talk among the EMT, β-catenin and NF-κB pathways. To identify the underlying mechanisms of Capn4 activity in melanoma cells, we determined Capn4 expression by gene chip and immunohistochemistral analyses in melanoma tissues and cells in vitro. The extent of apoptosis as determined by TUNEL assay, DAPI staining, and cleaved-caspase-3 assay was increased in human melanoma cells in which Capn4 expression had been knocked down when compared with untreated cells. Transwell assays and xenograft tumorigenicity studies were also performed to assess the effects of Capn4 on migration and invasion in vitro and tumor growth in vivo, respectively. The levels of β-catenin, vimentin, E-cadherin and N-cadherin were altered in human melanoma cells as determined by western blot analysis assay. Our study demonstrated that Capn4 is an underlying target for melanoma treatment.

Nonadherence to antipsychotic medication is a major health concern. Identification of risk factors associated with nonadherence is a useful initial step toward designing an effective intervention. This study compared the characteristics of medication-adherent and -nonadherent outpatients with schizophrenia in a Chinese community setting.In a naturalistic, multicenter, and cross-sectional design, 601 outpatients with schizophrenia served by the National Continuing Management and Intervention Program for Psychoses (the "686 program") were surveyed from June 2013 to January 2014 in four Chinese cities. On the basis of self-reported behavior, the patients were divided into medication-adherent and -nonadherent groups. Logistic regression analyses were performed to identify potential risk factors associated with nonadherence.The analyses included 554 patients, 20% of whom were considered to be nonadherent. Compared with the adherent group, the nonadherent group had a longer period of untreated psychosis (odds ratio [OR]=1.09), lower body mass index (OR=.94), higher rate of rural residency (OR=2.01), and lower monthly household income per capita (OR=.94/100 renminbi) (p.05 by hierarchical analysis). Other characteristics (age, gender, occupation, education, marital status, living with family, age at initial presentation of symptoms, duration of illness, and type of antipsychotic medication) did not differ significantly between the groups.Medication-adherent and -nonadherent groups differed significantly in some social and treatment characteristics. These findings may be useful in informing the development of strategies for reducing medication nonadherence.

Monoamine oxidase A (MAOA) plays a critical role in the metabolism of monoamine neurotransmitters including serotonin (5-HT), norepinephrine (NE), and dopamine (DA). Genetic studies have found an association between MAOA and attentiondeficit/hyperactivity disorder (ADHD), especially impulsivity. However, there has been inconsistency among studies which may be due to the complexity and heterogeneity of ADHD, including its sexual dimorphism and the presence of several subtypes. We conducted transmission disequilibrium tests (TDTs) in 1,253 trios and found no association between five single nucleotide polymorphisms (SNPs) of MAOA with ADHD in general or in the predominantly inattentive (ADHD-I) or combined types (ADHD-C), but with the predominantly hyperactive/impulsivity type (ADHD-HI). The association with MAOA was restricted to males, especially males with ADHD-HI. Logistic regression analyses of data from 1,824 cases and 957 controls did not indicate any association. We used analysis of covariance to analyze the association between MAOA genotype with the ‘‘inhibit’’ factor of the Behavior Rating Inventory of Executive Function (BRIEF) in 640 probands and performance on the Stroop test in 810 probands. Probands homozygous for risk alleles found in the TDT test had higher ‘‘inhibit’’ scores on the BRIEF scale which represents more severe impulsivity; this results also was restricted to males. No association was found with Stroop test performance. In conclusion, our results provide some evidence that MAOA may be associated with the ADHD-HI subtype and support the association between MAOA and impulsivity, which may be a potential endophenotype of ADHD. However, the results were strongly influenced by gender. � 2011 Wiley-Liss, Inc.

Introduction Obesity hypoventilation syndrome (OHS) is a major respiratory complication caused by severe obesity, being associated with significant morbidity, negative impacts on quality of life and reduced survival if not treated appropriately. Positive airway pressure therapy is the first-line treatment for OHS although the optimal modality remains unclear. The goal of this study is to identify the efficacy of home bilevel positive airway pressure therapy by comparison to continuous positive airway pressure therapy and determine the best strategy for patients with OHS. Methods and analysis This study will be conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 statement. We will search the following databases: PubMed, Web of Science, EMBASE, Cochrane Central Register of Controlled Trials and CINAHL. Ongoing studies will be identified through the ClinicalTrials.gov and WHO International Clinical Trials Registry Platform Search Portal. Grey literature will be recognised through Google Scholar and other search engines. Only randomised controlled trials meeting the eligibility criteria will be included. The risk of bias of the included studies will be evaluated through the Cochrane Collaboration’s tool. RevMan V.5.3.5 software will be used for data analysis. The Q statistic and I 2 index will be used for investigating heterogeneity, and subgroup analysis or sensitivity analysis will be used to explore the source of heterogeneity. In addition, the Grading of Recommendations Assessment, Development and Evaluation system will be used to inspect the quality of evidence. Ethics and dissemination Ethics approval is not required because this study contains no primary data collected from humans. This systematic review and meta-analysis will be submitted to a peer-reviewed journal for publication. PROSPERO registration number CRD42017078369.

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BACKGROUND This study describes a simple and stable cervical heterotopic kidney transplantation method in rats that uses artery sleeve anastomosis, vein cuff anastomosis and preserving-bag techniques. METHODS The donor graft, consisting of kidney, renal vein (RV), renal artery (RA) and a ureterocystic flap, was removed en bloc and perfused in situ. The donor RA was end-to-end anastomosed to the recipient left common carotid artery (CCA) using a sleeve anastomosis, and the donor RV was connected to the recipient right external jugular vein (EJV) using a cuff technique. During the vascular anastomosis, the kidney graft was placed in a lactated Ringer's solution ice-water preserving bag. The donor bladder patch was exteriorized to form cervical cutaneous stoma. RESULTS A total of 104 heterotopic renal transplantations were performed, which included pre-experimental (62 operations) and experimental stages (42 operations). The success rates of the two stages were 80.6% and 95.2%, respectively. The time for surgery was 40 +/- 6 min, the average time for donor surgery was 20 +/- 5 min, the preparation time for the graft was 8 +/- 2 min, the operative time for the recipient was 18 +/- 3 min that included the time for the arterial anastomosis (5 +/- 2 min) and venous anastomosis (2 +/- 1 min), the cold ischaemic time of the graft was 15 +/- 3 min and the warm ischaemic time of the graft was 2 +/- 1 min. CONCLUSION We developed an easy and reliable model of cervical heterotopic kidney transplantation that may provide a useful tool for investigating kidney transplantation rejection and retransplantation pathology.

Adrenal angiomyolipoma is an extremely rare tumor, although computed tomography (CT) or magnetic resonance imaging findings of adrenal angiomyolipoma have been reported, there are no reports regarding integrated fluorine-18-fluorodeoxyglucose positron emission tomography and computed tomography (18F-FDG PET/CT) imaging. We report a case of adrenal angiomyolipoma showing a significantly high uptake of 18F-fluorodeoxyglucose on PET/CT study. The maximal standardized uptake value (SUV) of the lesion was 18.8. Adrenal angiomyolipoma can show an intense uptake in FDG-PET/CT, and this can easily be confused with a malignant disease. Adrenal angiomyolipoma should be considered as one of the differential diagnoses in cases of adrenal incidentaloma with intense FDG uptake.

Background In 2005, China implemented a demonstration program known as “686” to scale-up nation-wide basic mental health services designed to improve access to evidence-based care and to promote human rights for people with severe mental disorders. As part of the 686 Program, teams “unlocked” and provided continuous mental health care to people with severe mental disorders who were found in restraints and largely untreated in their family homes. We implemented a nation-wide two-stage follow-up study to measure the effectiveness and sustainability of the “unlocking and treatment” intervention and its impact on the well-being of patients’ families. Methods 266 patients unlocked from 2005 in “686” demonstration sites across China were recruited in Stage One of the study in 2009. In 2012, 230 of the 266 cases were re-interviewed (the Stage Two study). Outcome measures included the patient medication adherence and social functioning, family burden ratings, and relocking rate. We utilized pre-post tests to analyze the changes over time following the unlocking efforts. Results 96% of patients were diagnosed with schizophrenia. Prior to unlocking, their total time locked ranged from two weeks to 28 years, with 32% having been locked multiple times. The number of persons regularly taking medicines increased from one person at the time of unlocking to 74% in 2009 and 76% in 2012. Pre-post tests showed sustained improvement in patient social functioning and significant reductions in family burden. Over 92% of patients remained free of restraints in 2012. Conclusion Practice-based evidence from our study suggests an important model for protecting the human rights of people with mental disorders and keeping them free of restraints can be achieved by providing accessible, community based mental health services with continuity of care. China’s “686” Program can inform similar efforts in low-resource settings where community locking of patients is practiced.

Amniotic membrane transplantation (AMT) is considered a substantial treatment option in the management of ocular surface disorders. However, several inherent drawbacks still remain. The present study devised a novel implantable composite biomaterial of fibrin glue-double layer Amniotic membrane (AM) and evaluated the biomechanical properties and effects on corneal surface reconstruction in alkali-burned rabbit model. Biomechanic parameters were calculated by an electronic universal testing machine. Corneal alkali burning was done in the right eyes of thirty rabbits, which were randomized into three groups of ten animals each. The eyes in group 1 underwent fibrin glue-double layer AMT, the eyes in group 2 underwent ordinary single layer AMT, and the eyes in group 3 (control group) did not undergo any surgical procedure. Healing of corneal epithelial defect, extent of corneal vascularization and corneal clarity were assessed and compared at two time points. One month after surgery, animals were killed and the eyes were processed for histopathology. The fibrin glue-double layer AM composites had more ideal biomechanical properties. In fibrin glue-double layer AM group, the rate of epithelial healing, vascularization inhibition and corneal clarity was significantly better than the other two groups. Novel fibrin glue-double layer AMT with corneal alkali burns is more effective and useful for ocular surface reconstruction and has great potential applications.

Attention-deficit/hyperactivity disorder (ADHD) typically emerges before 7 years of age and may persist into adolescence or adulthood. The adolescent outcome can be classified into four types, including non-remission, syndromatic remission, symptomatic remission, and functional remission. Genetic factors are believed to contribute to symptom stability and change across development, so adolescent outcome may be a sub-phenotype for molecular genetic studies of ADHD. Serotonin system genes are prime candidates for this sub-phenotype, since the development of this neurotransmitter system parallels the course of ADHD. The current study examined the association between adolescent outcome in ADHD and serotonin system genes, including the -1438A>G polymorphism of the serotonin 2A receptor gene (HTR2A) and the -759C>T polymorphism of the serotonin 2C receptor gene (HTR2C). The -1438A>G polymorphism was found to be related to remission in ADHD, especially functional remission (P = 0.029). Due to potential phenotypic and etiologic heterogeneity in ADHD, the results of this study must be replicated in additional samples before they can be generalized to other populations.

Glucagon-like peptide 2 (GLP-2) is an intestinal epithelium-specific growth factor. However, its protective effects and related mechanism on the small intestine injured by ischemia-reperfusion (I/R) in mice remain unclear. This study aimed to reveal the effects of GLP-2 and its functional relationship with uncoupling protein 2 (UCP2) on the small intestine after I/R injury in mice. Male Balb/c mice were given GLP-2 (250 microg/kg/day, ip) for 3 days and underwent 30 min of superior mesenteric artery occlusion followed by 1 hr of reperfusion on day 4. Histological damage, bacterial translocation, diamine oxidase, and malondialdehyde level were assessed, and UCP2 expression was measured by immunohistochemistry and Western blot. GLP-2 attenuated the intestinal histological damage caused by I/R and increased the villous height by 28% and the crypt depth by 10%, respectively. Compared to the I/R group, diamine oxidase activity was increased, the incidence of bacterial translocation and malondialdehyde level were decreased, and UCP2 expression was increased in GLP-2-treated mice. GLP-2 protected the small intestine from I/R injury and increased UCP2 expression. These results suggested that effects of GLP-2 should be related to the upregulation of mitochondrial UCP2, which antagonized reactive oxygen species production.

ObjectivesThe Severe Respiratory Insufficiency (SRI) questionnaire is the best assessment tool for health-related quality of life in patients with chronic obstructive pulmonary disease (COPD) receiving non-invasive positive pressure ventilation (NIPPV). This study aimed to translate the SRI Questionnaire into Chinese and to validate it.DesignProspective validation study.Setting and participantsA total of 149 participants with chronic hypercapnic COPD receiving NIPPV completed the study.MethodsThe SRI questionnaire was translated into Chinese using translation and back-translation. Reliability was gauged using Cronbach’s α coefficient. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to assess construct validity. Content validity was confirmed by evaluating the relationship between the score of each item and the total score of the relevant subscale.ResultsCronbach’s α coefficients for each subscale and summary scale were above 0.7. Using EFA, one factor was extracted from the anxiety and summary scales and two factors were extracted from the remaining six subscales. Based on the EFA results, subsequent CFA revealed a good model fit for each subscale, but the extracted factors of each subscale were correlated. Content validity was confirmed by the good relationship between the score of each item and the total score of the relevant subscale.ConclusionThe Chinese version of the SRI questionnaire is valid and reliable for patients with chronic hypercapnic COPD receiving NIPPV in China.Trial registration numberNCT02499718.

Introduction: Mycosis fungoides is a kind of malignant lymphoma arising from T cells, but primarily occurs in skin, and it is the most common type of cutaneous lymphoma. Mycosis fungoides (MF) is a rare non-Hodgkin lymphoma but the most common type of primary cutaneous T-cell lymphomas. Because of unknown etiology and mechanism, and lack of typical clinical and histophysiological manifestations, the final diagnosis of MF is currently dependent on pathology and immunohistochemistry. Subsequently, tumor staging is very important. Different approaches would be taken according to varying degrees of cutaneous and extracutaneous lesions. Computed tomography (CT) scan has been chosen to stage tumors customarily. However, CT could only provide morphological information and analyze lymphadenopathy by the size criteria. 18F-flurodeoxyglucose positron emission tomography/computed tomography (PET/CT) could provide morphological information and metabolic conditions simultaneously, which is helpful to locate and stage lesion. Conclusion: 18F-flurodeoxyglucose PET/CT could identify cutaneous and extracutaneous lesions in patients with MF. It could provide the range of lesions and biopsy target.

The catechol-O-methyltransferase (COMT) gene contains a functional polymorphism (Val158Met) affecting the activity of the enzyme, and the monoamine oxidase A (MAOA) gene contains a VNTR polymorphism (MAOA-uVNTR) that affects the transcription of the gene. COMT and MAOA each contribute to the enzymatic degradation of dopamine and noradrenaline. Prefrontal cortical (PFC) function, which plays an important role in individual cognitive abilities, including intelligence, is modulated by dopamine. Since our previous association studies between attention deficit hyperactivity disorder (ADHD) and these two functional polymorphisms consistently showed the low activity alleles were preferentially transmitted to inattentive ADHD boys, the goal of the present study was to test the hypothesis that the interaction between COMT Val158Met and MAOA-uVNTR may affect the intelligence in a clinical sample of Chinese male ADHD subjects (n = 264). We found that the COMT x MAOA interaction significantly predicted full scale (FSIQ) and performance (PIQ) IQ scores (P = 0.039, 0.011); the MAOA-uVNTR significantly predicted FSIQ, PIQ and verbal IQ (VIQ) (P = 0.009, 0.019, 0.038); COMT Val158Met independently had no effect on any of the IQ scores. Only the COMT x MAOA interaction for PIQ remained significant after a Bonferroni correction. Among all combined genotypes, the valval-3R genotype predicted higher intelligence, (average 106.7 +/- 1.6, 95% C.I. 103.7-109.8 for FSIQ), and the valval-4R predicted lower intelligence (average 98.0 +/- 2.3, 95% C.I. 93.5-102.6 for FSIQ). These results suggest that there is an inverted U-shaped relationship between intelligence and dopaminergic activity in our sample. Our finding that gene-gene interaction between COMT and MAOA predicts the intelligence of ADHD boys in China is intriguing but requires replication in other samples.

Our goal was to establish a simple and stable cervical heterotopic small intestinal transplantation (SIT) rat model that minimizes mortality. Methods. The graft was removed en bloc consisting of small intestine, portal vein (PV), and donor superior mesenteric artery. The graft was perfused in situ and the gut lumen irrigated during the operation. The donor artery was end-to-end anastomosed to the recipient left common carotid artery using a sleeve technique, and the donor vein to the recipient right external jugular vein using a cuff technique. The proximal and distal ends of the graft were formed as cervical cutaneous stomas. Results. Among 106 intestinal transplantations, 40 were a formal experimental group, displaying a survival rate of 95%. Surgery lasted 70 10 minutes. The average time for the arterial anastomosis and the venous anastomosis was 5 2 minutes and 2 1 minutes, respectively. Two rats died due to late anastomotic hemorrhage or intestinal fistula; 38 survived more than 6 months. Conclusion. The cervical heterotopic technique has the advantages of being easier and faster to perform with shorter cold ischemia time and higher graft survival rate as well as fewer complications.

Attention deficit hyperactivity disorder (ADHD) is a common neuropsychiatric condition with strong genetic basis. Recent work in China indicated that ADHD may be linked to Xp1-2 in the Han Chinese population. The gene encoding monoamine oxidase B (MAOB), the main enzyme degrading dopamine in the human brain, is located in this region. The current study sequenced the exons and the 5' and 3' flanking regions of the MAOB gene and found four common variants including 2276C>T and 2327C>T in exon 15, rs1799836 in intron 13 and rs1040399 in 3'-UTR. We assessed the association of these variants with ADHD in 548 trios collected from 468 males and 80 females probands. TDT analysis showed that alleles of each polymorphism were preferentially transmitted to probands (rs1799836, P = 3.28E-15; rs1040399, P = 1.87E-6; 2276T>C or 2327T>C, P = 2.20E-6) and haplotype-based TDT analyses also found distorted transmission. In conclusion, this study provides the strongest evidence for the involvement of MAOB gene in the etiology of ADHD to date, at least in Han Chinese population.

A dysfunction of the central noradrenergic system has long been suggested to be involved in attention-deficit/hyperactivity disorder (ADHD). Pharmacological evidence from animal studies and clinical practice has identified the alpha-2A adrenergic receptor gene (ADRA2A) as a candidate gene in ADHD. Some findings from Caucasian populations seem to support a role for this gene in ADHD. The current study first examined the association of the ADRA2A MspI and DraI polymorphisms with ADHD in the Han Chinese population, which differs quite substantially from the Caucasian population in the frequencies of alleles at these polymorphisms. No biased transmission of alleles of either polymorphism was observed using transmission disequilibrium test (TDT) analysis in a sample of 268 nuclear families with an ADHD proband; however, haplotype analysis only identified a trend toward over-transmission of the M/C haplotype to probands with the combined subtype of ADHD (χ2 = 3.233, P = 0.072). The mm genotype of the MspI polymorphism was also marginally related (P = 0.051) to lower ADHD symptom scores in a sample of 559 Chinese children with ADHD, which is inconsistent with data from Caucasian samples. Our results provide weak evidence for a possible role of ADRA2A in ADHD symptom expression. © 2006 Wiley-Liss, Inc.

Background There are three childhood disruptive behavior disorders (DBDs), attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD). The most common comorbid disorder in ADHD is ODD. DSM-IV describes three ADHD subtypes: predominantly inattentive type (ADHD-IA), predominantly hyperactive-impulsive type (ADHD-HI), and combined type (ADHD-C). Prior work suggests that specific candidate genes are associated with specific subtypes of ADHD in China. Our previous association studies between ADHD and functional polymorphisms of COMT and MAOA, consistently showed the low transcriptional activity alleles were preferentially transmitted to ADHD-IA boys. Thus, the goal of the present study is to test the hypothesis that COMT Val158Met and MAOA-uVNTR jointly contribute to the ODD phenotype among Chinese ADHD boys. Methods 171 Chinese boys between 6 and 17.5 years old (mean = 10.3, SD = 2.6) with complete COMT val158met and MAOA-uVNTR genotyping information were studied. We used logistic regression with genotypes as independent variables and the binary phenotype as the dependent variable. We used p < 0.05 as the level of nominal statistical significance. Bonferroni correction procedures were used to adjust for multiple comparisons. Results Our results highlight the potential etiologic role of COMT in the ADHD with comorbid ODD and its predominately inattentive type in male Chinese subjects. ADHD with comorbid ODD was associated with homozygosity of the high-activity Val allele, while the predominantly inattentive ADHD subtype was associated with the low-activity Met allele. We found no evidence of association between the MAOA-uVNTR variant and ADHD with comorbid ODD or the ADHD-IA subtype. Conclusion Our study of attention deficit hyperactivity disorder comorbid oppositional defiant disorder and its predominately inattentive type highlights the potential etiologic role of COMT for ADHD children in China. But we failed to observe an interaction between COMT and MAOA, which suggests that epistasis between COMT and MAOA genes does not influence the phenotype of ADHD-IA with comorbid ODD in a clinical sample of Chinese male subjects. To confirm our findings further studies with a larger number of subjects and healthy controls are needed.