PE/PPE mutations in the transmission of Mycobacterium tuberculosis in China revealed by whole genome sequencing.

OBJECTIVE: This study aims to examine the impact of PE/PPE gene mutations on the transmission of Mycobacterium tuberculosis (M. tuberculosis) in China. METHODS: We collected the whole genome sequencing (WGS) data of 3202 M. tuberculosis isolates in China from 2007 to 2018 and investigated the clustering of strains from different lineages. To evaluate the potential role of PE/PPE gene mutations in the dissemination of the pathogen, we employed homoplastic analysis to detect homoplastic single nucleotide polymorphisms (SNPs) within these gene regions. Subsequently, logistic regression analysis was conducted to analyze the statistical association. RESULTS: Based on nationwide M. tuberculosis WGS data, it has been observed that the majority of the M. tuberculosis burden in China is caused by lineage 2 strains, followed by lineage 4. Lineage 2 exhibited a higher number of transmission clusters, totaling 446 clusters, of which 77 were cross-regional clusters. Conversely, there were only 52 transmission clusters in lineage 4, of which 9 were cross-regional clusters. In the analysis of lineage 2 isolates, regression results showed that 4 specific gene mutations, PE4 (position 190,394; c.46G > A), PE_PGRS10 (839,194; c.744 A > G), PE16 (1,607,005; c.620T > G) and PE_PGRS44 (2,921,883; c.333 C > A), were significantly associated with the transmission of M. tuberculosis. Mutations of PE_PGRS10 (839,334; c.884 A > G), PE_PGRS11 (847,613; c.1455G > C), PE_PGRS47 (3,054,724; c.811 A > G) and PPE66 (4,189,930; c.303G > C) exhibited significant associations with the cross-regional clusters. A total of 13 mutation positions showed a positive correlation with clustering size, indicating a positive association. For lineage 4 strains, no mutations were found to enhance transmission, but 2 mutation sites were identified as risk factors for cross-regional clusters. These included PE_PGRS4 (338,100; c.974 A > G) and PPE13 (976,897; c.1307 A > C). CONCLUSION: Our results indicate that some PE/PPE gene mutations can increase the risk of M. tuberculosis transmission, which might provide a basis for controlling the spread of tuberculosis.

PTPMT1 protects cardiomyocytes from necroptosis induced by γ-ray irradiation through alleviating mitochondria injury.

Radiation-induced heart disease (RIHD) progresses over time and may manifest decades after the initial radiation exposure, which is associated with significant morbidity and mortality. The clinical benefit of radiotherapy is always counterbalanced by an increased risk of cardiovascular events in survivors. There is an urgent need to explore the effect and the underlying mechanism of radiation-induced heart injury. Mitochondrial damage widely occurs in irradiation-induced injury, and mitochondrial dysfunction contributes to necroptosis development. Experiments were performed using induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and rat H9C2 cells to investigate the effect of mitochondrial injury on necroptosis in irradiated cardiomyocytes and to further elucidate the mechanism underlying radiation-induced heart disease and discover possible preventive targets. After γ-ray irradiation, the expression levels of necroptosis markers were increased, along with higher oxidative stress and mitochondrial injury. These effects could be abated by overexpression of protein tyrosine phosphatase, mitochondrial 1 (PTPMT1). Inhibiting oxidative stress or increasing the expression of PTPMT1 could protect against radiation-induced mitochondrial injury and then decrease the necroptosis of cardiomyocytes. These results suggest that PTPMT1 may be a new target for the treatment of radiation-induced heart disease.NEW & NOTEWORTHY Effective strategies are still lacking for treating RIHD, with unclear pathological mechanisms. In cardiomyocytes model of radiation-induced injuries, we found γ-ray irradiation decreased the expression of PTPMT1, increased oxidative stress, and induced mitochondrial dysfunction and necroptosis in iPSC-CMs. ROS inhibition attenuated radiation-induced mitochondrial damage and necroptosis. PTPMT1 protected cardiomyocytes from necroptosis induced by γ-ray irradiation by alleviating mitochondrial injury. Therefore, PTPMT1 might be a potential strategy for treating RIHD.

Development and performance evaluations of an HER-2 kit.

Objective To develop a kit for detecting human epidermal growth factor receptor 2 (HER-2) in the human body. Methods The HER-2 kit was evaluated based on an automated magnetic particle chemiluminescence platform. The kit was developed using the double antibody sandwich-complexation method. Results The kit showed a linear range of 0.01-800 ng/mL, with a linear R2 of >0.999. The limit of the blank was 0.0039 ng/mL, and the precision at 1.00 ng/mL was 9.4%. The recovery rate at 10.00 ng/mL was 97.81-101.81%. The negative serum reference range was 0-8.23 ng/mL. Conclusions The kit had a wide linear range, high accuracy, good precision, and high sensitivity, indicating that it has good application prospects.

Fibroblasts and mouse breast cancer cells can form cellular aggregates in improved soft agar culture medium.

We aimed to build cellular aggregates of TS/A and normal fibroblasts (LX-2) or CAFs (ME-iLX-2), verifying the value of this model in the screening of anticancer drugs and demonstrating the effect of CD44 on aggregate formation. We improved soft agar culture medium to coculture CAFs (NFs) and TS/A and compared the amount and area of cellular aggregates. Eugenol was added to this model to test its value. The transcription of human CD44 was analyzed through RT-qPCR. Cellular aggregates were formed, and both the amount and area of aggregates in the TS/A-ME-iLX-2 coculture group were higher than those in other groups. The eugenol inhibited the formation of TS/A-fibroblasts aggregates. Human CD44 was highly transcripted in TS/A-ME-iLX-2 aggregates. Cocultured cellular aggregates of fibroblasts and TS/A were successfully formed in the improved soft agar culture medium, and the promotion effect of CAFs on cancer cells was further confirmed. The eugenol test showed its value in the screening of anticancer drugs. The RT-qPCR results demonstrated the important effect of CD44 on aggregate formation.

Preliminary study on miRNA in prostate cancer.

OBJECTIVE: To screen for miRNAs differentially expressed in prostate cancer and prostate hyperplasia tissues and to validate their association with prostate cancer. METHODS: Patients diagnosed by pathology in the Department of Urology of the First Affiliated Hospital of Xinjiang Medical University from October 2021 to June 2022 were selected, and their general clinical information, blood samples, and prostate tissue samples were collected. miRNA microarray technology was performed to obtain differentially expressed miRNAs in prostate cancer and hyperplasia tissues, and miRNAs to be studied were screened by microarray results and review of relevant literature. The detection of miRNA expression in the patients' blood and prostate tissue samples was measured. The miRNA-222-mimics were transfected into PC3 cells, and cell biology experiments such as CCK8, scratch, Transwell, and flow cytometry were performed to detect the effects of overexpressed miRNA-222 on the growth and proliferation, invasive ability, apoptotic ability, and metastatic ability of prostate cancer cells. RESULTS: The results of the miRNA microarray showed that there were many differentially expressed miRNAs in prostate cancer and hyperplasia tissues, and four miRNAs, miRNA-144, miRNA-222, miRNA-1248, and miRNA-3651 were finally selected as the subjects by reviewing relevant literature. The results showed that the expression of miRNA-222 in prostate cancer tissues was lower than that in prostate hyperplasia tissues (P < 0.05). The expression of miRNA-222, miRNA-1248, and miRNA-3651 in blood samples of prostate cancer patients was lower than that in prostate hyperplasia patients (P < 0.05). The analysis results indicated that the f/t ratio and the relative expression of miRNA-222 and miRNA-1248 were independent influences of prostate cancer (P < 0.05), in which overexpression of miRNA-222 decreased the proliferative, invasive, and metastatic abilities of PC3 cells and enhanced the level of apoptosis of cancer cells. CONCLUSIONS: Although there was no significant change in the overall incidence of prostate cancer in this study, significant changes occurred in the incidence of prostate cancer with different characteristics. In addition, the nomogram prediction model of prostate cancer-specific survival rate constructed based on four factors has a high reference value, which helps physicians to correctly assess the patient-specific survival rate and provides a reference basis for patient diagnosis and prognosis evaluation.

Ginger polysaccharide promotes myeloid-derived suppressor cell apoptosis by regulating lipid metabolism.

Recently, targeting myeloid-derived suppressor cells (MDSCs) which mainly play an immunosuppressive role in tumor microenvironment has become a hot spot in tumor immunotherapy. This study focuses on biological effect of ginger polysaccharide extracted from natural plants on promoting apoptosis of MDSCs by regulating lipid metabolism. An MTT assay was used to detect the inhibitory effect of ginger polysaccharide on the growth of an MDSC-like cell line (MSC-2). The apoptosis-promoting effect of ginger polysaccharide on MSC-2 cells was detected by flow cytometry. Expression levels of apoptosis proteins (caspase 9 and Bcl-2) and lipid metabolism enzymes (fatty acid synthase (FASN) and diacylglycerol acyltransferase 2) in MSC-2 cells treated with different concentrations of ginger polysaccharide were detected by western blot assay. Nile red staining was used to quantitatively detect the effect of ginger polysaccharide on lipid droplet synthesis. Ginger polysaccharide inhibited proliferation of MSC-2 cells and promoted their apoptosis by upregulating pro-apoptotic caspase 9 protein, downregulating anti-apoptotic Bcl-2 protein, inhibiting expression of FASN and diacylglycerol acyltransferase 2 (key enzymes in fatty acid synthesis and lipid droplet formation, respectively). Ginger polysaccharide promoted apoptosis of MDSCs by regulating key lipid metabolism enzymes, inhibiting fatty acid synthesis and lipid droplet accumulation, and reducing the energy supply of cells.

Cinnamaldehyde inhibits cytokine storms induced by the ORF3a protein of SARS-CoV-2 via ROS-elimination in activated T cells.

Cytokine storms are the cause of complications in patients with severe COVID-19, and it becomes the target of therapy. Several natural compounds were selected to screen the inhibitory effect on T-cell proliferation by Fluorescence-Activated Cell Sorting (FACS) and cytokine production by enzyme-linked immunosorbent assay (ELISA). Open reading frame 3a (ORF3a) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulates the specific T-cell activation model in vivo and in vitro. The coculture system included the macrophage cell line RAW264.7 and splenocytes. Reactive oxygen species (ROS) levels and glycolysis in T cells were evaluated. Cinnamaldehyde effectively inhibits cytokine storms both in vitro and in vivo. It decreased inflammatory cytokine (such as IFN-γ, TNF-α, IL-6, and IL-2) production by murine peripheral blood cells upon direct stimulation with ConA, after immunization with the MHV-A59 virus or ORF3a peptide from SARS-CoV-2. Cinnamaldehyde restored the percentage of T cells, which was originally decreased in the peripheral blood and splenocytes of ORF3a-immunized mice. In a coculture system, cinnamaldehyde reduced the secretion of inflammatory cytokines from macrophages in a T-cell dependent manner. Furthermore, cinnamaldehyde decreased the ROS level in activated T cells, which in turn reduced glycolysis and the activation of T cells. Cinnamaldehyde can be used as a candidate molecule for COVID-19.

Association between diagnostic delay and prognosis of pulmonary tuberculosis in Shandong, China: a retrospective study.

BACKGROUND: Tuberculosis (TB) is one of the main infectious diseases that seriously threatens global health, while diagnostic delay (DD) and treatment dramatically threaten TB control. METHODS: Between 2005 and 2017 in Shandong, China, we enrolled pulmonary tuberculosis (PTB) patients with DD. DD trends were evaluated by Joinpoint regression, and associations between PTB patient characteristics and DD were estimated by univariate and multivariate logistic regression. The influence of DD duration on prognosis and sputum smear results were assessed by Spearman correlation coefficients. RESULTS: We identified 208,822 PTB cases with a median DD of 33 days (interquartile range (IQR) 18-63). The trend of PTB with DD declined significantly between 2009 and 2017 (annual percent change (APC): - 4.0%, P = 0.047, 2009-2013; APC: - 6.6%, P = 0.001, 2013-2017). Patients aged > 45 years old (adjusted odds ratio (aOR): 1.223, 95% confidence interval (CI) 1.189-1.257, 46-65 years; aOR: 1.306, 95% CI 1.267-1.346, > 65 years), farmers (aOR: 1.520, 95% CI 1.447-1.596), and those with a previous treatment history (aOR: 1.759, 95% CI 1.699-1.821) were prone to developing long DD (> 30 days, P < 0.05). An unfavorable outcome was negatively associated with a short DD (OR: 0.876, 95% CI 0.843-0.910, P < 0.001). Sputum smear positive rate and unfavorable outcomes were positively correlated with DD duration (Spearman correlation coefficients (rs) = 1, P < 0.001). CONCLUSIONS: The DD situation remains serious; more efficient and comprehensive strategies are urgently required to minimize DD, especially for high-risk patients.

Association between body mass index and newly diagnosed drug-resistant pulmonary tuberculosis in Shandong, China from 2004 to 2019.

BACKGROUND: Drug-resistant tuberculosis (DR-TB), obesity, and malnutrition are growing public health problems in the world. However, little has discussed the impact of different BMI status on the emergence of TB drug resistance. We aimed to explore the drug-resistant profiles of DR-TB and its clinical predictors among underweight, overweight or obesity population. METHODS: 8957 newly diagnosed TB cases with drug susceptibility results and BMI data in Shandong China, from 2004 to 2019 were enrolled. Multivariable and univariable logistic regression models were applied to investigate the impact of BMI on different drug-resistance. Clinical predicators and drug-resistant profiles of DR-TB among obesity, underweight, normal TB group were also described. RESULTS: Among 8957 TB cases, 6417 (71.64%) were normal weight, 2121 (23.68%) were underweight, 373 (4.16%) were overweight, and 46 (0.51%) were obese. The proportion of drug resistance and co-morbidity among normal weight, underweight, overweight, obese TB groups were 18.86%/18.25%/20.38%/23.91% (DR-TB), 11.19%/11.74%/9.65%/17.39% (mono-resistant tuberculosis, MR-TB), 3.41%/3.06%/5.36%/0.00% (multidrug resistant tuberculosis, MDR-TB), 4.21%/3.39%/5.36%/6.52% (polydrug resistant tuberculosis, PDR-TB), 10.57%/8.44%/19.57%/23.91% (co-morbidity), respectively. Compared with normal weight group, underweight were associated with lower risk of streptomycin-related resistance (OR 0.844, 95% CI 0.726-0.982), but contributed to a higher risk of MR-TB (isoniazid) (odds ratio (OR) 1.347, 95% CI 1.049-1.730; adjusted OR (aOR) 1.31, 95% CI 1.017-1.686), P < 0.05. In addition, overweight were positively associated with MDR-TB (OR 1.603, 95% CI 1.002-2.566; aOR 1.639, 95% CI 1.02-2.633), isoniazid + rifampicin + streptomycin resistance (OR 1.948, 95% confidence interval (CI): 1.061-3.577; aOR 2.113, 95% CI 1.141-3.912), Any isoniazid + streptomycin resistance (OR 1.472, 95% CI 1.013-2.14; aOR 1.483, 95% CI 1.017-2.164), P < 0.05. CONCLUSIONS: The higher risk of MDR-TB, isoniazid + rifampicin + streptomycin resistance, Any isoniazid + streptomycin resistance, and co-morbidity among overweight population implies that routine screening for drug sensitivity and more attention on co-morbidity among overweight TB cases may be necessary. In addition, underweight TB cases have a higher risk of isoniazid resistance. Our study suggests that an in-depth study of the interaction between host metabolic activity and infection of DR-TB may contribute more to novel treatment options or preventive measures, and accelerate the implementation of the STOP TB strategy.

Ambient air pollutants, diabetes and risk of newly diagnosed drug-resistant tuberculosis.

BACKGROUND: Drug-resistant tuberculosis (DR-TB), diabetes and exposure to air pollution are thought to be important threat to human health, but no studies have explored the effects of ambient air pollutants on DR-TB when adjusting diabetes status so far. METHODS: We performed a study among 3759 newly diagnosed TB cases with drug-susceptibility testing results, diabetes status, and individual air pollution data in Shandong from 2015 to 2019. Generalized linear mixed models (GLMM) including three models (Model 1: without covariates, Model 2: adjusted by diabetes status only, Model 3: with all covariates) were applied. RESULTS: Of 3759 TB patients enrolled, 716 (19.05%) were DR-TB, and 333 (8.86%) had diabetes. High exposure to O3 was associated with an increased risk of RFP-resistance (Model 2 or 3: odds ratio (OR) = 1.008, 95% confidence intervals (CI): 1.002-1.014), ethambutol-resistance (Model 3: OR = 1.015, 95%CI: 1.004-1.027) and any rifampicin+streptomycin resistance (Model 1,2,3: OR = 1.01, 95%CI: 1.002-1.018) at 90 days. In contrast, NO2 was associated with a reduced risk of DR-TB (Model 3: OR = 0.99, 95%CI: 0.981-0.999) and multidrug-resistant TB (MDR-TB) (Model 3: OR = 0.977, 95%CI: 0.96-0.994) at 360 days. Additionally, SO2 (Model 1, 2, 3: OR = 0.987, 95%CI: 0.977-0.998) showed a protective effect on MDR-TB at 90 days. PM2.5 (90 days, Model 2: OR = 0.991, 95%CI: 0.983-0.999), PM10 (360 days, Model 2: OR = 0.992, 95%CI: 0.985-0.999) had protective effects on any RFP+SM resistance. CONCLUSIONS: O3 contributed to an elevated risk of TB resistance but PM2.5, PM10, SO2, NO2 showed an inverse effect. Air pollutants may affect the development of drug resistance among TB cases by adjusting the status of diabetes.

[Relationship between sleep disorders and hypertension in oil workers in Karamay City].

OBJECTIVE: To investigate the effect of sleep disorders on hypertension in oil workers and its mediating effect analysis. METHODS: Between June and September 2019, 1420 workers aged 20-60 years(745 males and 675 females; 384 aged 30 years, 563 aged 30-45 years and 473 aged 45 years) from six oilfield bases in Karamay City, Xinjiang Uygur Autonomous Region were surveyed using a two-stage randomized whole-group sampling method. Their current conditions, and the information on gender, age, ethnicity, personal monthly income, education level, job title, smoking, alcohol consumption, height, weight, and shift work of the oil workers were investigated by the basic questionnaire. The Pittsburgh Sleep Index was used to assess the sleep status, and the Logistic regression model was used to analyze the influencing factors of hypertension, and the Process program(version 3.3) was used to conduct the mediating effect model test. RESULTS: (1) The detection rate of sleep disorders was 52.5% and the prevalence of hypertension was 16.3%, with 21.6%(161) higher in women than 10.5%(71) in men(χ~2=31.877, P& lt; 0.001). The prevalence of hypertension increased with increasing age and body mass index(BMI)(χ~2=25.117, P& lt; 0.001), 20.1%(149) in the sleep disorder group were higher than 12.2%(83) in the non-sleep disorder group(χ~2=16.113, P& lt; 0.001). (2) After adjusting for gender, age, ethnicity, education, personal monthly income, smoking, alcohol consumption, shift work and BMI, sleep disorders(OR=1.686, 95% CI 1.232-2.308), gender(OR=1.565, 95% CI 1.035-2.367), age(OR_(30-45)=1.710, 95% CI 1.085-2.697; OR_(& gt; 45)=1.717, 95% CI 1.055-2.797), shift work(OR=2.698, 95% CI 1.889-3.855), BMI(OR_(24.0-27.9)=2.557, 95% CI 1.736-3.765; OR_(≥28.0)=4.001, 95% CI 2.553-6.318) increased the risk of hypertension. (3) The result of stratified analysis showed that with age(OR_(30-45)=1.642, 95% CI 1.019-2.645; OR_(& gt; 45)=1.998, 95% CI 1.223-3.263) and BMI(OR_(24.0-27.9)=1.652, 95% CI 1.079-2.528; OR_(≥28.0)=2.259, 95% CI 1.165-4.381) increased, the risk of hypertension due to sleep disorders increased. Sleep disorders(OR=2.002, 95% CI 1.336-2.936) were also risk factors for hypertension in the shift work group. (4) The result of the mediating effect test showed that there was a mediating effect(P& lt; 0.05) between sleep disorders in age(ß=0.240, Z=2.239), shift work(ß=0.656, Z=3.999), and BMI(ß=0.516, Z=7.258) and hypertension. CONCLUSION: Sleep disorders may be a risk factor affecting hypertension in oil workers in Karamay City, and there were mediating effects between age, shift work, and BMI and hypertension.

Curcumin promotes cancer-associated fibroblasts apoptosis via ROS-mediated endoplasmic reticulum stress.

Cancer-associated fibroblasts (CAFs) play an important role in tumorigenesis, development, and migration. Eliminating CAFs or reducing their tumor-promoting activity is beneficial for tumor immunotherapy. Curcumin is a natural polyphenol derived from turmeric, which has been shown to inhibit the growth of many types of tumor. In this study, we explored the effect of curcumin on prostate-CAFs and its underlying molecular mechanism. The effect of curcumin on CAFs was measured using MTT assay and plate colony formation assay. Flow cytometry was used to detect cell apoptosis, ROS, Cell cycle, and mitochondrial membrane potential (ΔΨm) changes after curcumin treatment. Western Blot was used to detect changes in expression levels of related proteins in CAFs after curcumin stimulation. Colorimetry was used to detect the change of caspase 3 activity. The mRNA levels of Bims, Puma, ATF4 and CHOP were determined by qRT-PCR. We found that curcumin induced the apoptosis and cell cycle arrest of CAFs, which is mainly caused by the ROS-mediated endoplasmic reticulum stress pathway. For mechanism, the up-regulation of ROS caused by curcumin triggers endoplasmic reticulum stress of CAFs through the PERK-eIF2α-ATF4 axis. Our study suggests that curcumin selectively inhibits prostate-CAFs by inducing apoptosis and cell cycle arrest in G2-M phase, indicating a novel application of curcumin in tumor therapy.

Case-Control Study on the Interaction Effects of rs10757278 Polymorphisms at 9p21 Locus and Traditional Risk Factors on Coronary Heart Disease in Xinjiang, China.

OBJECTIVE: To study the interaction effects of rs10757278 polymorphisms at 9p21 locus and traditional risk factors on coronary heart disease (CHD) in Xinjiang, China. METHODS: This case-control study consecutively enrolled 310 unrelated consecutive CHD patients aged 18-70 years old. All study participants were recruited between January and December 2017 from The Heart Center of The First Affiliated Hospital of Xinjiang Medical University. CHD patients were confirmed by coronary angiography (≥50% diameter stenosis in at least one of the major coronary arteries) according to the American Heart Association criteria for the confirmation of CHD. Healthy subjects were randomly selected from the occupational population, who received physical examination in our hospital and matched to cases on the basis of age (±3 years) and sex, those without medical history of cardiovascular diseases, and 536 subjects were selected as the control group after medical history inquiry, physical examination, cardiac ultrasound, electrocardiogram, and other blood biochemical examinations in the hospital. The occupational stress was evaluated by an effort-reward imbalance questionnaire. An epidemiological survey was conducted to collect clinical data. Chi-squared test, analysis of variance, and binary logistic regression analysis were adopted. RESULTS: Both the case and the control groups showed significant difference in smoking, drinking, physical activity, hypertension, diabetes mellitus, family history of CHD, and body mass index (BMI) (all P < 0.05); prevalence of CHD was not related to occupational stress. There was no significant difference in occupational stress level between the 2 groups (P > 0.05); Differences in rs10757278 genotype between the case group and the control groups were statistically significant; binary logistic regression analysis was used to evaluate the risk factors of CHD. After adjustment for age and sex, significant increased risk effects for CHD were found to be associated with smoking [odds ratio (OR) = 2.311; 95% confidence interval (CI): 1.04-2.499; P < 0.001], physical exercise (OR = 1.365; 95% CI: 1.137-1.639; P < 0.001), hypertension (OR = 4.627; 95% CI: 2.165-10.764; P < 0.001), family history of CHD (OR = 4.103; 95% CI: 3.169-6.892; P < 0.001), BMI (OR = 2.484; 95% CI: 2.036-3.03; P < 0.001), and GG genotype at rs10757278 (OR = 1.978; 95% CI: 1.413-2.769; P < 0.001); We noted that a significant interaction association between GG genotype at rs10757278 and CHD differs across categories of smoking, hypertension, family history of CHD, and BMI. CONCLUSION: GG genotype at rs10757278 may be a risk factor for CHD. And there are interaction effects between GG genotype of rs10757278 in region 9p21 gene and traditional risk factors.

Effects of Occupational Stress and Circadian CLOCK Gene Polymorphism on Sleep Quality of Oil Workers in Xinjiang, China.

BACKGROUND This study investigated the effect of occupational stress and circadian clock gene polymorphism on sleep disorder of oil workers in Xinjiang, China. MATERIAL AND METHODS We enrolled 2300 Xinjiang oil workers who had been working for at least 1 year. The Chinese revised version of the Occupational Stress Questionnaire (OSI-R), the Pittsburgh Sleep Quality Index (PSQI), and General Survey Questionnaire were used. A total of 308 subjects were selected for stress hormone measurements and gene polymorphism analysis of the circadian clock genes CLOCK, PER2, and PER3. RESULTS The occupational stress scores were influenced by sex, smoking, marital status, age, and work type. Different work shift groups and different professional title groups had statistically significant sleep disorder incidences (P<0.05). The middle and high occupational stress groups had significantly higher subjective sleep quality, total PSQI scores, daytime dysfunction factor scores, and sleep disorder than in the low occupational stress group (P<0.05). CLOCK gene rs1801260 locus carrying TC genotype (OR=0.412, 95% CI=0.245-0.695), and CLOCK gene rs6850524 locus carrying GC and CC genotypes decreased sleep disorder risk (OR1=0.357, 95% CI1=0.245-0.695; OR2=0.317, 95% CI2=0.128-0.785). The main factors affecting the sleep quality of oil workers were length of service, individual strain capacity, glucocorticoid levels, Per3 gene, and the rs6850524 loci of CLOCK gene. CONCLUSIONS Occupational stress has an adverse effect on the sleep quality of workers. CLOCK gene and Per3 gene may increase risk of sleep disorders.

Association between economic development level and tuberculosis registered incidence in Shandong, China.

BACKGROUND: Tuberculosis (TB) is one of the major infectious diseases that seriously endanger people's health. In Shandong province, the relationship between the level of economic development and TB incidence has not been studied. This study aims to provide more research basis for the government to prevent and control TB by exploring the impact of different economic factors on TB incidence. METHODS: By constructing threshold regression model (TRM), we described the extent to which different economic factors contribute to TB registered incidence and differences in TB registered incidence among seventeen cities with different levels of economic development in Shandong province, China, during 2006-2017. Data were retrieved from the China Information System for Disease Control and Prevention. RESULTS: Per capita medical expenditure (regression coefficient, -0.0314462; SD, 0.0079305; P > |t|, 0.000) and per capita savings (regression coefficient, 0.0001924; SD, 0.0000566; P > |t|, 0.001) passed the significance test at the level of 1%.They are the two economic indicators that have the greatest impact on TB registered incidence. Through the threshold test, we selected the per capita savings as the threshold variable. In the three stages of per capita savings (<9772.8086 China Yuan(CNY); 9772.8086-33,835.5391 CNY; >33,835.5391 CNY), rural per capita income always has a significant negative impact on the TB registered incidence (The regression coefficients are - 0.0015682, - 0.0028132 and - 0.0022253 respectively. P is 0.007,0.000 and 0.000 respectively.).In cities with good economies, TB registered incidence was 38.30% in 2006 and dropped to 25.10% by 2017. In cities with moderate economies, TB registered incidence peaked in 2008 at 43.10% and dropped to 27.1% by 2017.In poorer cities, TB registered incidence peaked in 2008 at 56.30% and dropped to 28.9% in 2017. CONCLUSION: We found that per capita savings and per capita medical expenditure are most closely related to the TB incidence. Therefore, relevant departments should formulate a more complete medical system and medical insurance policy to effectively solve the problem of "difficult and expensive medical treatment". In order to further reduce the TB incidence, in addition to timely and accurate diagnosis and treatment, it is more important for governments to increase investment in medicine and health care.

Primary drug resistance of mycobacterium tuberculosis in Shandong, China, 2004-2018.

BACKGROUND: Primary drug-resistant tuberculosis (DR-TB) has contributed to a significant health and economic burden on a global scale, especially in China. we sought to estimate epidemiological characteristics of primary DR-TB in China from 2004 to 2018. METHODS: Eleven thousand four hundred sixty-seven newly diagnosed and 1981 retreated TB cases with drug susceptibility data were included. Chi-Square test for trends, linear regression, a joinpoint regression model and temporal trend in proportions of the different resistance patterns were carried out. RESULTS: The proportion of primary DR-TB and mono-resistant TB (MR-TB) in China had reduced by more than 12% since 2004, and were 21.38%, 13.35% in 2018 respectively. Among primary DR-TB cases (2173,18.95%), the percentage of multiresistant TB (MDR-TB, from 5.41 to 17.46%), male (from 77.03 to 84.13%), cavity (from 13.51 to 43.92%), rifampicin(RFP)-resistant TB (from 8.11 to 26.98%), streptomycin(SM)-resistant TB (from 50.00 to 71.43%) increased significantly (P < 0.05). On the contrary, the proportion of female, non-cavity, isoniazide(INH)-resistant TB (from 55.41 to 48.15%) and MR-TB (from 82.43 to 62.43%) decreased significant (P < 0.05). The primary drug resistance rate among female, cavity, smoking, drinking, 15 to 44 year-old TB subgroups increased by 0.16, 6.24, 20.95, 158.85, 31.49%, respectively. The percentage of primary DR-TB, RFP-resistant TB dropped significantly during 2004-2007 in Joinpoint regression model. CONCLUSION: The total rate of drug resistance among new TB cases showed a downward trend in Shandong, China, from 2004 to 2018. Primary drug resistance patterns were shifting from female, non-cavity, INH-resistant TB, and MR-TB groups to male, cavity, RFP/SM-resistant TB, and MDR-TB groups. Considering the rising drug resistance rate among some special population, future control of primary DR-TB in China may require an increased focus on female, cavity, smoking, drinking, or 15 to 44 year-old TB subgroups.

Epidemiological characteristics of pulmonary tuberculosis among children in Shandong, China, 2005-2017.

BACKGROUND: Diagnosis of tuberculosis (TB) in children is challenging. Epidemiological data of childhood pulmonary tuberculosis (PTB) are urgently needed. METHODS: We described trends in epidemiology, clinical characteristics, and treatment outcomes in seven cities of Shandong province, China, during 2005-2017. Data were collected from the China Information System for Disease Control and Prevention. RESULTS: Among 6283 (2.4% of all PTB) PTB cases aged < 18 years, 56.5% were male patients, 39.3% were smear-positive and 98.6% were new cases. The overall incidence of childhood PTB declined (7.62 to 3.74 per 100,000) during 2005-2017, with a non-significant change of annual percentage after 2010. While the incidence of smear-positive PTB (6.09 to 0.38 per 100,000 population) decreased significantly, but the incidence of smear-negative PTB (1.52 to 3.36 per 100,000 population) increased significantly during 2005-2017. The overall treatment success occurred among 94.2% childhood PTB. Ten children (0.2%) died. CONCLUSION: The overall incidence of childhood PTB declined significantly with the disease burden shifting from smear-positive PTB to smear-negative PTB. The discrepancies between notifications and estimations in both TB morbidity and mortality of children need to be addressed urgently.

[Effect of occupational stress on hypertension in desert oilfield workers].

OBJECTIVE: To explore influence of occupational stress on hypertension in Xinjiang Uygur Autonomous Region desert oilfield workers. METHODS: Cluster sampling was applied. A total of 1280 petroleum workers from 3 oil fields were used in Karamay City, Xinjiang. Occupational Stress Scale(OSI-R) was used to evaluate occupational stress and analyze the impact of occupational stress on hypertension. RESULTS: With the increase of occupational stress, the prevalence rate of hypertension is increasing(χ~2=21. 078, P<0. 001). Multivariate analysis showed that the risk of high blood pressure in the occupational task was 1. 562 times(95%CI 1. 072-2. 277)as high as that of the less occupational group, and the risk of high blood pressure in the group with strong individual tension reaction was 1. 701 times(95%CI 1. 158-2. 498)as much as that of the weak group(P<0. 05). Analysis of influencing factors of hypertension showed that the risk of high blood pressure in the shift was 1. 389 times(95%CI 1. 115-1. 730)as high as those without the shift, in the frequent drinkers was 1. 877 times(95%CI 1. 300-2. 710)that of the non drinkers, in the high salt patients was 1. 286 times(95%CI 1. 107-1. 691)that of the low salt, in the obese was 1. 564 times(95%CI 1. 249-2. 216)that of the normal people, and in the highly occupational stress was 1. 976 times(95%CI 1. 641-2. 336)as high as the low occupational stress. CONCLUSION: Heavy occupational tasks and strong individual strain can increase the risk of hypertension in desert oilfield workers. Shift, drinking history, salt consumption, BMI and occupational stress were the influencing factors of hypertension in desert oilfield workers.

Association of glucocorticoid receptor gene polymorphism and occupational stress with hypertension in desert petroleum workers in Xinjiang, China.

BACKGROUND: The aim of this study was to investigate the occupational stress and hypertension in desert petroleum workers in Xinjiang, and to analyze the association of occupational stress and glucocorticoid receptor (GR) gene polymorphism with the presence of hypertension. METHODS: Using cluster sampling, 1280 desert petroleum workers of 3 petroleum fields in Xinjiang Karamay were randomly selected as the target group for this study. According to the inclusion criteria, a total of 1080 workers were included as the baseline for this study. We followed these workers for 2 years to investigate their occupational stress and hypertension. The polymorphism of GR gene was detected by polymerase chain reaction-restriction fragment length polymorphism. We applied appropriate statistical methods to analyze the association of occupational stress and glucocorticoid receptor (GR) gene polymorphism with the presence of hypertension. RESULTS: After 2 years of follow-up, there were 995 desert petroleum workers in the queue. The study showed that the incidence of hypertension in desert petroleum workers were 19.4%. Compared with the baseline data, the level of occupational stress increased, and with the increase of occupational stress, the incidence of hypertension was gradually increasing. A positive relationship was observed in the GR BCL1 gene polymorphisms and hypertension. Relative to the CC genotype, carries of the GG genotype had a significantly higher risk of hypertension (OR = 2.830). With the combination of genotype CG and GG, carries of CG and GG increased the risk of hypertension (adjusted OR = 2.238, 95%CI:1.104-4.940). There was no significant association between GR G678S gene polymorphisms and hypertension. CONCLUSION: GR gene polymorphism and occupational stress of desert petroleum workers were important risk factors for hypertension.

An Asparagus polysaccharide fraction inhibits MDSCs by inducing apoptosis through toll-like receptor 4.

Despite decades of research, malignant tumors are extremely difficult to eliminate with conventional methods. Although surgical resection potentially eradicates the problem, only a few cases are suitable for operation, and other approaches often involve harmful consequences. Revolutionary methods are desperately needed to improve patient outcomes and diminish harmful side effects. Myeloid-derived suppressor cells (MDSCs), downregulators of the innate and adaptive immune systems, have been widely studied over the past 2 decades. MDSCs inhibit the antitumor immune response by suppressing T cell proliferation, cytokine production, and tumor cell killing. With MDSCs becoming novel targets in cancer therapy, our research has focused on the anti-MDSC function of Asparagus polysaccharide (AP), extracted from asparagus, a traditional Chinese herb. In this study, we have used MDSCs isolated from the spleen of mice with colon cancer as an in vitro model to assess the efficacy of AP. Treatment of MDSCs with AP significantly decreased cell proliferation and induced apoptotic cell death through a toll-like receptor 4 dependent way. Subsequent studies showed that the AP treatment enhanced the expression of Bax and Caspase-9 and inhibited the expression of Bcl-2, suggesting that AP induced apoptosis in the MDSCs via the intrinsic pathway. Altogether, the results showed that AP exhibited a significant anti-MDSC activity and attenuated suppression of the antitumor immune response, thereby indicating its potential use in cancer therapy.