eDOTS: Improving the Treatment of Pulmonary Tuberculosis in Xinjiang, China.

Purpose: To increase pulmonary tuberculosis (PTB) treatment adherence in Xinjiang Region, an electronic DOTS (eDOTS) system developed was applied and evaluated. Methods: An eDOTS system comprised electronic medicine boxes, mobile phones and a central processing platform. Between April and June 2016, persons with active PTB (PAPTB) were recruited from villages and a city and were prescribed a six-month course of antibiotics using either DOTS or eDOTS. Treatment adherence rate and chest X-ray digital radiography (DR) score were used to evaluate usefulness of eDOTS. Results: A total 167 PAPTB were recruited with 81 participants from villages and 86 from neighbourhoods. Of the 81 village patients, 43 (53%) used eDOTS and 38 (47%) used DOTS. Among the 86 patients from neighbourhoods, 50 (58%) used eDOTS and 36 (42%) used DOTS. After 6 months of treatment, the average treatment compliance of the village patients who used eDOTS were 47.0%±20.5% compared to 26.7%±21.1% who used DOTS (t=-4.475, p<0.001). The patients using eDOTS from both the villages and city had significantly lower X-ray DR scores than the patients using DOTS by 1.81 points, 95% CI (0.72-2.90) and 1.05 points, 95% CI (0.15-1.95), respectively. Conclusion: eDOTS is an effective means of managing the treatment of active PTB patients through daily reminding and monitoring of patient compliance. Ease of contact with doctors and special education programs encouraged PAPTB to complete their treatment course as required.

Treatment adherence among sputum smear-positive pulmonary tuberculosis patients in Xinjiang, China: a prospective study.

BACKGROUND: Despite great effort to control tuberculosis (TB), low treatment adherence threatens the success of drug therapy, increases the risk of TB transmission, and leads to the development of drug resistance. The present study assessed anti-TB treatment adherence in sputum smear-positive TB patients and examined the risk factors for poor patient adherence to identify targets for intervention. METHODS: We monitored and followed up TB patients who were diagnosed between July 2014 and June 2015 in Xinjiang, China. A total of 8289 sputum smear-positive TB patients were included in this study. All patients registered their information during the first hospital visit or with the Centers for Disease Control, had regular follow-up visits, and accepted the anti-TB treatment. Insufficient re-examination adherence was defined as undergoing fewer than the recommended three sputum smear examinations during the treatment course. RESULTS: Among 8289 patients, 3827 men (84.4% of male patients) and 3220 women (85.7% of female patients) had good adherence during treatment follow-up. 1242 patients (15.0%) did not complete regular follow-up. 332 (4.0%) patients lost contact. An adjusted logistic regression model showed that ethnicity, household address, treatment classification, patient source, and the actual management were significantly associated with non-adherence. CONCLUSION: The Xinjiang TB epidemic situation remains grim. Smear-positive patients had a higher proportion of non-adherence, which increased treatment difficulties and the risk of death from TB. Relevant medical departments should strengthen their supervision and interventions during the TB treatment process to improve patient adherence to anti-TB treatment.

Seasonality of active tuberculosis notification from 2005 to 2014 in Xinjiang, China.

OBJECTIVES: Xinjiang is one of the highest TB-burdened provinces of China. A time-series analysis was conducted to evaluate the trend, seasonality of active TB in Xinjiang, and explore the underlying mechanism of TB seasonality by comparing the seasonal variations of different subgroups. METHODS: Monthly active TB cases from 2005 to 2014 in Xinjiang were analyzed by the X-12-ARIMA seasonal adjustment program. Seasonal amplitude (SA) was calculated and compared within the subgroups. RESULTS: A total of 277,300 confirmed active TB cases were notified from 2005 to 2014 in Xinjiang, China, with a monthly average of 2311±577. The seasonality of active TB notification was peaked in March and troughed in October, with a decreasing SA trend. The annual 77.31% SA indicated an annual mean of additional TB cases diagnosed in March as compared to October. The 0-14-year-old group had significantly higher SA than 15-44-year-old group (P<0.05). Students had the highest SA, followed by herder and migrant workers (P<0.05). The pleural TB cases had significantly higher SA than the pulmonary cases (P <0.05). Significant associations were not observed between SA and sex, ethnic group, regions, the result of sputum smear microcopy, and treatment history (P>0.05). CONCLUSION: TB notification in Xinjiang shows an apparent seasonal variation with a peak in March and trough in October. For the underlying mechanism of TB seasonality, our results hypothesize that winter indoor crowding increases the risk of TB transmission, and seasonality was mainly influenced by the recent exogenous infection rather than the endogenous reactivation.

Resveratrol induces cell cycle arrest and apoptosis in human eosinophils from asthmatic individuals.

Eosinophils exert a number of inflammatory effects through the degranulation and release of intracellular mediators, and are considered to be key effector cells in allergic disorders, including asthma. In order to investigate the regulatory effects of the natural polyphenol, resveratrol, on eosinophils derived from asthmatic individuals, the cell counting Kit­8 assay and flow cytometry analysis were used to determine cell proliferation and cell cycle progression in these cells, respectively. Cellular apoptosis was detected using annexin V-fluorescein isothiocyanate/propidium iodide double­staining. The protein expression levels of p53, p21, cyclin­dependent kinase 2 (CDK2), cyclin A, cyclin E, Bim, B­cell lymphoma (Bcl)­2 and Bcl­2­associated X protein (Bax) were measured by western blot analysis following resveratrol treatment. The results indicated that resveratrol effectively suppressed the proliferation of eosinophils from asthmatic patients in a concentration­ and time­dependent manner. In addition, resveratrol was observed to arrest cell cycle progression in G1/S phase by increasing the protein expression levels of p53 and p21, and concurrently reducing the protein expression levels of CDK2, cyclin A and cyclin E. Furthermore, resveratrol treatment significantly induced apoptosis in eosinophils, likely through the upregulation of Bim and Bax protein expression levels and the downregulation of Bcl­2 protein expression. These findings suggested that resveratrol may be a potential agent for the treatment of asthma by decreasing the number of eosinophils.

[Association of copy number variation of exon 11 of IL-23 receptor gene with susceptibility to tuberculosis among Chinese Uygurs].

OBJECTIVE: To assess the association of copy number variations (CNVs) of exon 11 of IL-23 receptor gene with susceptibility to active pulmonary tuberculosis among Chinese Uygurs. METHODS: In this study, 250 subjects with active pulmonary tuberculosis (PTB) and 250 normal controls were recruited. A paired case-control study was conducted in the Chinese Uygur population in Xinjiang and the CNV of IL-23R was analyzed using Taqman real-time PCR. RESULTS: The study showed that the frequencies of different copy number in exon 11 of IL-23R between PTB and control groups were statistically significant (χ(2)=13.35, P<0.01). There were significant difference in CNV of exon 11 in IL-23R between PTB patients and controls (χ(2)=14.95, P<0.01, OR=2.875, 95%CI: 1.655-4.994). The increase of copy number in exon 11 of IL-23R showed significantly different between PTB and control groups (χ(2)=10.475, P=0.0012, OR=2.611, 95%CI: 1.437-4.744). CONCLUSION: The CNV of exon 11 in IL-23R is associated with PTB in the Chinese Uygur population. The increase of the copy number in exon 11 of IL-23R may be a risk factor for PTB in Chinese Uygurs.

Socio-Demographic Predictors and Distribution of Pulmonary Tuberculosis (TB) in Xinjiang, China: A Spatial Analysis.

OBJECTIVES: Xinjiang is one of the high TB burden provinces of China. A spatial analysis was conducted using geographical information system (GIS) technology to improve the understanding of geographic variation of the pulmonary TB occurrence in Xinjiang, its predictors, and to search for targeted interventions. METHODS: Numbers of reported pulmonary TB cases were collected at county/district level from TB surveillance system database. Population data were extracted from Xinjiang Statistical Yearbook (2006~2014). Spatial autocorrelation (or dependency) was assessed using global Moran's I statistic. Anselin's local Moran's I and local Getis-Ord statistics were used to detect local spatial clusters. Ordinary least squares (OLS) regression, spatial lag model (SLM) and geographically-weighted regression (GWR) models were used to explore the socio-demographic predictors of pulmonary TB incidence from global and local perspectives. SPSS17.0, ArcGIS10.2.2, and GeoDA software were used for data analysis. RESULTS: Incidence of sputum smear positive (SS+) TB and new SS+TB showed a declining trend from 2005 to 2013. Pulmonary TB incidence showed a declining trend from 2005 to 2010 and a rising trend since 2011 mainly caused by the rising trend of sputum smear negative (SS-) TB incidence (p<0.0001). Spatial autocorrelation analysis showed the presence of positive spatial autocorrelation for pulmonary TB incidence, SS+TB incidence and SS-TB incidence from 2005 to 2013 (P <0.0001). The Anselin's Local Moran's I identified the "hotspots" which were consistently located in the southwest regions composed of 20 to 28 districts, and the "coldspots" which were consistently located in the north central regions consisting of 21 to 27 districts. Analysis with the Getis-Ord Gi* statistic expanded the scope of "hotspots" and "coldspots" with different intensity; 30 county/districts clustered as "hotspots", while 47 county/districts clustered as "coldspots". OLS regression model included the "proportion of minorities" and the "per capita GDP" as explanatory variables that explained 64% the variation in pulmonary TB incidence (adjR2 = 0.64). The SLM model improved the fit of the OLS model with a decrease in AIC value from 883 to 864, suggesting "proportion of minorities" to be the only statistically significant predictor. GWR model also improved the fitness of regression (adj R2 = 0.68, AIC = 871), which revealed that "proportion of minorities" was a strong predictor in the south central regions while "per capita GDP" was a strong predictor for the southwest regions. CONCLUSION: The SS+TB incidence of Xinjiang had a decreasing trend during 2005-2013, but it still remained higher than the national average in China. Spatial analysis showed significant spatial autocorrelation in pulmonary TB incidence. Cluster analysis detected two clusters-the "hotspots", which were consistently located in the southwest regions, and the "coldspots", which were consistently located in the north central regions. The exploration of socio-demographic predictors identified the "proportion of minorities" and the "per capita GDP" as predictors and may help to guide TB control programs and targeting intervention.

The variations of IL-23R are associated with susceptibility and severe clinical forms of pulmonary tuberculosis in Chinese Uygurs.

BACKGROUND: The incidence of tuberculosis (TB) remains high among Chinese Uygurs (a long-dwelling ethnic minority in Xinjiang) in China and the variants in IL-23R likely contribute to individual's diversity in host response during infection. METHODS: A hospital based one to one matched case-control study was performed to assess the role of single nucleotide polymorphisms (SNPs) and copy number variation (CNV) of IL-23R in susceptibility and clinical features of pulmonary TB in Chinese Uygurs. Thirteen SNPs in IL-23R were genotyped by multiplex SNaPshot and a CNV was analyzed using Taqman real-time PCR in 250 pairs of pulmonary TB patients and controls. RESULTS: The SNP rs7518660 (OR = 4.78, 95% CI 3.14-8.52) and the CNV in IL23R (OR = 2.75, 95% CI 1.51-4.98) were significantly associated with susceptibility to pulmonary TB. The SNP rs11465802 (OR = 3.23, 95% CI 1.85-5.62) was significantly associated with drug-resistance and the SNP rs1884444 (OR = 3.61, 95% CI 1.90-6.85) was significantly related to cavitary lesion in Chinese Uygurs. CONCLUSIONS: Our study shows for the first time that SNP and CNV in IL23R were associated with susceptibility, drug resistance and cavity formation of pulmonary TB. Our findings indicate that these IL-23R polymorphisms may be considered as risk factors for active pulmonary TB and its severe clinical forms.

[Polymorphisms of IL-23 receptor gene are associated with susceptibility to pulmonary tuberculosis and drug-resistant pulmonary tuberculosis].

OBJECTIVE: To explore the associations of interleukin-23 (IL-23) receptor gene polymorphisms, susceptibility to pulmonary tuberculosis and drug-resistant pulmonary tuberculosis (TB). METHODS: For this paired case-control study, 13 single nucleotide polymorphisms (SNPs) in IL-23R gene were genotyped by multiplex SNaPshot with samples from 250 pairs of culture positive pulmonary TB patients and healthy controls. And the relationship between genotype, allele, haplotype and susceptibility to pulmonary tuberculosis was analyzed. RESULTS: Two SNPs of IL-23R gene (rs10889677 and rs7518660) (OR = 1.53, 95% CI: 1.01-2.31; OR = 6.25, 95% CI: 3.85-10.00) were significantly associated with susceptibility to pulmonary TB and one SNP (rs11465802) (OR = 2.90; 95% CI: 1.69-4.98) was associated with drug-resistant pulmonary TB in the Chinese Uygur population. CONCLUSIONS: Two SNPs of IL-23R gene, rs10889677 and rs7518660, may be the risk factors of pulmonary tuberculosis. And rs11465802 may be a risk factor of drug-resistant pulmonary tuberculosis in Chinese Uygur population.

[Relationship between disintegrin and metalloproteinase gene polymorphism of bronchial asthma and its severity in Uygur population].

OBJECTIVE: To explore the relationship between disintegrin and metalloproteinase (ADAM33) gene polymorphism of bronchial asthma and its severity in Xinjiang Uygur population. METHODS: From January to December 2009, a total of 126 consecutive Uighur asthmatics with a definite diagnosis at First Affiliated Hospital of Xinjiang Medical University were assigned into intermittent mild (n = 62), moderate (n = 39) and severe (n = 25) groups according to the severity of illness. The control group was a 1: 1 paired population from healthy subjects matched similarly with regards to gender, race, residence and age (with a difference <5 years). The ADAM33 gene polymorphisms of F+1, S+1, T1, T2 and V4 locus allele in each group were tested by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: In ADAM33, the distribution of T1, T2 and V4 locus allele in asthmatics and controls had a significant difference (χ² = 8.064, P = 0.018; χ² = 8.013, P = 0.018 and χ² = 11.737, P = 0.003). The distribution of allelic frequency showed that all T1 (C), T2 (A) and V4 (G) locus allele increased the relative risk degree of asthmatics (OR = 2.080, 2.139 and 1.912). The distribution frequency of T1 (TC and TT), T2 (AG and GG), V4 (GG and CC) genotypes in mild, moderate and severe groups had significant differences (all P < 0.05).Linkage disequilibrium analysis showed that in asthmatics, the presence of Hap2 (CATGC) was much lower than controls (20.4% vs 30.4%; χ² = 6.597, P = 0.010) while Hap4 (CACAC) and Hap5 (TACAG) were much higher than those in controls (9.6% vs 4.8% and 6.8% vs 2.8%; χ² = 4.545, P = 0.033 and χ² = 4.377, P = 0.036). CONCLUSIONS: The ADAM33 gene polymorphism of T1, T2 and V4 locus allele may be associated with asthma and its severity in Xinjiang. And Uighur population may have both susceptible and protective haplotypes of asthmatics.

Polymorphisms of the ADAM33 gene and chronic obstructive pulmonary disease risk: a meta-analysis.

BACKGROUND: The T1 (rs2280091), S1 (rs3918396) and S2 (rs528557) polymorphisms in a disintegrin and metalloprotease (ADAM33) gene has been implicated in susceptibility of chronic obstructive pulmonary disease (COPD). But, a number of studies have reported inconclusive results. The aim of this study is to investigate the relationship between T1 (rs2280091), S1 (rs3918396) and S2 (rs528557) polymorphisms in ADAM33 gene and COPD risk by meta-analysis. METHODS: We searched PubMed database, Embase database, Chinese National Knowledge Infrastructure database and Wanfang database, covering all studies till September 5, 2012. Statistical analysis was performed using software METAGEN (STATA 12.0) and Revman5.0. RESULTS: A total of 2139 COPD cases and 3765 controls in 10 case-control studies were included in this study. The results showed that S2 (rs528557) and T1 (rs2280091) polymorphisms did not result in an increased or a decreased risk of COPD. The analysis described in this report demonstrated that S1 (rs3918396) polymorphism (GG + AG vs AA) was significantly associated with the total and Asian. Odds ratio (OR)total = 1.27 [95% confidence interval (CI) 1.03-1.56, P = 0.03], ORAsian = 1.44 (95% CI 1.13-1.83, P = 0.003) but not with Caucasians. CONCLUSIONS: This meta-analysis suggested that S1 (rs3918396) polymorphism of ADAM33 is associated with increased risk of COPD in Asian (China) but not in Caucasians. Future studies are needed to validate our conclusions.

Changes in water channel aquaporin 1 and aquaporin 5 in the small airways and the alveoli in a rat asthma model.

OBJECTIVES: To examine changes in aquaporin 1 (AQP1) and aquaporin 5 (AQP5) in the small airways and alveoli in a rat asthma model. METHOD: Forty Wistar rats were randomly divided into a control group and an ovalbumin (OVA) sensitization asthma model group. The distribution and expression of AQP1 and AQP5 in lung tissues were analyzed using immunohistochemistry (IHC), quantified the staining intensity by assessing integrated optical densities (IOD), and Western blotting (WB). RESULTS: IHC showed AQP1 was mainly distributed in sub-epithelial microvascular endothelial cells (MECs) and red blood cells. IOD values showed, in the asthma model group, the expression of AQP1 in alveolar MECs was lower than that in the control group (P<0.05); However, AQP1 expression in small airways sub-epithelial was higher than in the control group (P<0.05). The WB indicated that AQP1 expression in the asthma model group was 57% lower than in the control group (P<0.05). AQP5 was mainly distributed in the non-ciliated epithelial cells of the small airways and the apical membranes of type I and type II epithelial cells. IOD values showed, in asthma model group, the expression of AQP5 increased in small airways epithelium (P<0.05), and decreased in alveolar epithelium (P<0.05). The WB showed a 36% reduction in AQP5 expression compared with the control group (P<0.05). CONCLUSION: AQP1 and AQP5 increased in small airways in rats with experimentally induced asthma, indicating that they may be involved in the formation of submucosal edema and mucus hypersecretion. Decreased AQP1 and AQP5 in pulmonary alveoli may be related to increased alveolar liquid viscosity and the formation of mucus plugs.