The Predictive Value of the Monocyte-to-Lymphocyte Ratio and Monocyte-to-Haematocrit Ratio for Cardiac Rupture Patients with Acute Myocardial Infarction: A Propensity Score Matching Analysis.

BACKGROUND: Cardiac rupture (CR) is a serious complication of acute myocardial infarction (AMI). We aimed to explore the predictive value of blood cell parameters for identifying CR in patients with AMI using the introduction of propensity score matching (PSM). METHODS: This retrospective study enrolled patients who were diagnosed with AMI from January 2013 to May 2020. A total of 109 patients with CR were included, and 327 hospitalized non-CR patients were randomly selected at a 1:3 ratio. Based on the 1:1 nearest neighbour matching method by using SPSS, the covariances of the two groups were balanced. After PSM, the independent risk factors for CR were selected by using multivariate logistic regression analysis, and receiver operating characteristic (ROC) curve analysis was applied to evaluate the predictive value of blood cell parameters for CR. Ninety cases were matched successfully in each of the two groups. RESULTS: Among the 180 patients with AMI after PSM, the results of multivariate logistic regression analysis showed that the monocyte-to-lymphocyte ratio (MLR) (OR = 3.57, 95% CI: 1.28-9.97, P = 0.015) and monocyte-to-haematocrit ratio (MHR) (OR = 1.80, 95% CI: 1.02-3.20, P = 0.043) were independently related to the risk of CR. Additionally, the MLR (area under the curve (AUC): 0.74) and MHR (AUC: 0.73) were useful for distinguishing CR patients after PSM. To differentiate CR patients from the control subjects, the optimal cut-offs of the MLR and MHR were 0.61 (63% sensitivity and 80% specificity) and 2.06 (57% sensitivity and 81% specificity), respectively. CONCLUSION: The blood cell parameters MLR and MHR were independently correlated with CR. Additional, the MLR and MHR were useful to predict CR in patients with AMI.

Neutrophil percentage-to-albumin ratio and monocyte-to-lymphocyte ratio as predictors of free-wall rupture in patients with acute myocardial infarction.

BACKGROUNDS: Free-wall rupture (FWR) has a high mortality rate. We aimed to find sensitive predictive indicators to identify high-risk FWR patients by exploring the predictive values of neutrophil percentage-to-albumin ratio (NPAR) and monocyte-to-lymphocyte ratio (MLR) on patients with acute myocardial infarction (AMI). METHODS: 76 FWR patients with AMI were collected, and then 228 non-CR patients with AMI were randomly selected (1:3 ratio) in this retrospective study. The independent influencing factors of FWR were evaluated by univariate and multivariate logistic regression analysis. The receiver-operating characteristic (ROC) curve analysis was applied to evaluate the predictive value of NPAR and MLR for FWR. RESULTS: According to the results of multivariate logistic regression analysis, emergency percutaneous coronary intervention (PCI) (OR = 0.27, 95% CI: 0.094-0.751, p = 0.012), angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) treatment (OR = 0.17, 95% CI: 0.044-0.659, p = 0.010), NPAR (OR = 2.69, 95% CI: 1.031-7.044, p = 0.043), and MLR (OR = 5.99, 95% CI: 2.09-17.168, p = 0.001) were the influencing factors of the FWR patients with AMI, independently. Additionally, the NPAR and MLR were the predictors of FWR patients, with AUC of 0.811 and 0.778, respectively (both p < 0.001). CONCLUSIONS: In summary, the emergency PCI and ACEI/ARB treatment were independent protective factors for FWR patients with AMI, while the increase of MLR and NPAR were independent risk factors. What's more, NPAR and MLR are good indicators for predicting FWR.

[Effect of breastfeeding on the development of infection-related diseases during hospitalization in late preterm infants in 25 hospitals in Beijing, China].

OBJECTIVE: To investigate the incidence rate of infectious diseases during hospitalization in late preterm infants in Beijing, China, as well as the risk factors for infectious diseases and the effect of breastfeeding on the development of infectious diseases. METHODS: Related data were collected from the late preterm infants who were hospitalized in the neonatal wards of 25 hospitals in Beijing, China, from October 23, 2015 to October 30, 2017. According to the feeding pattern, they were divided into a breastfeeding group and a formula feeding group. The two groups were compared in terms of general status and incidence rate of infectious diseases. A multivariate logistic regression analysis was used to investigate the risk factors for infectious diseases. RESULTS: A total of 1 576 late preterm infants were enrolled, with 153 infants in the breastfeeding group and 1 423 in the formula feeding group. Of all infants, 484 (30.71%) experienced infectious diseases. The breastfeeding group had a significantly lower incidence rate of infectious diseases than the formula feeding group (22.88% vs 31.55%, P=0.033). The multivariate logistic regression analysis showed that breastfeeding was an independent protective factor against infectious diseases (OR=0.534, P=0.004), while male sex, premature rupture of membranes, gestational diabetes mellitus, and asphyxia were risk factors for infectious diseases (OR=1.328, 5.386, 1.535, and 2.353 respectively, P < 0.05). CONCLUSIONS: Breastfeeding can significantly reduce the incidence of infectious diseases and is a protective factor against infectious diseases in late preterm infants. Breastfeeding should therefore be actively promoted for late preterm infants during hospitalization.

Prognostic significance of TPX2 and NIBP in esophageal cancer.

The expression of targeting protein for Xenopus kinesin-like protein 2 (TPX2) and NIK-IKK-ß binding protein (NIBP) in patients with esophageal cancer were investigated. A total of 250 samples of cancer tissue and 250 samples of adjacent normal tissue were collected from 250 patients who underwent radical resection of esophageal cancer in Weihai Central Hospital from March 2011 to February 2014. RT-qPCR was used to detect the relative expression of TPX2 and NIBP. The relative expression of TPX2 and NIBP in esophageal cancer tissues was statistically higher than those in adjacent normal tissues (P<0.05). TPX2 and NIBP levels in tumor tissues with lymph node metastasis were significantly higher than those in tissues without lymph node metastasis (P<0.05). There was a significant difference in the relative expression of TPX2 and NIBP in different degrees of infiltration (P<0.05). Tissues with a TPX2 level equal to or higher than the average TPX2 level (1.465) were divided into TPX2 high expression group, while tissues with a TPX2 level below the average were divided into TPX2 low expression group. The 5-year overall survival rate of TPX2 high expression group was significantly lower than that of TPX2 low expression group (P<0.05). Tissues with a NIBP level equal to or higher than the average NIBP level (0.498) were included in the NIBP high expression group, while tissues with a NIBP level below the average were included in the NIBP low expression group. The 5-year overall survival rate of NIBP high expression group was significantly lower than that of NIBP low expression group (P<0.05). TPX2, NIBP, TNM staging, lymph node metastasis, and degree of infiltration were independent prognostic factors affecting overall survival (P<0.05). In conclusion, owing to their high expression in esophageal cancer tissues, TPX2 and NIBP are potentially important biomarkers for the evaluation of TNM stage, metastasis, and prognosis of esophageal cancer.

miR-155-5p Promotes Progression of Acute Respiratory Distress Syndrome by Inhibiting Differentiation of Bone Marrow Mesenchymal Stem Cells to Alveolar Type II Epithelial Cells.

BACKGROUND We investigated whether microRNA-155-5p is involved in the differentiation of bone marrow mesenchymal stem cells (BMSCs) into alveolar type II epithelial (AT II) cells by regulating the Wnt signaling pathway, thus participating in the development of acute respiratory distress syndrome (ARDS). MATERIAL AND METHODS Serum levels of microRNA-155-5p in 50 ARDS patients and 50 normal controls were detected by quantitative real-time PCR (qRT-PCR). Marrow mesenchymal stem cells (MCSs) were isolated from mouse bone marrow and identified by flow cytometry. Subsequently, the effect of microRNA-155-5p on differentiation of BMSCs into AT II cells was evaluated by detecting the expression levels of AT II-specific genes. The expression levels of proteins in the Wnt signaling pathway after overexpression or knockdown of microRNA-155-5p were detected by Western blot. RESULTS Serum levels of microRNA-155-5p in ARDS patients were significantly higher than that in normal controls. Expression levels of AT II-specific genes were enhanced after downregulating microRNA-155-5p in BMSCs. MicroRNA-155-5p overexpression showed the opposite result. Furthermore, microRNA-155-5p inhibited the expression levels of proteins in the Wnt signaling pathway. CONCLUSIONS MicroRNA-155-5p can attenuate the differentiation of BMSCs into AT II cells by inhibiting the Wnt signaling pathway, thus promoting the progression of ARDS.

Synthesis and Anticancer Activities of Glycyrrhetinic Acid Derivatives.

A total of forty novel glycyrrhetinic acid (GA) derivatives were designed and synthesized. The cytotoxic activity of the novel compounds was tested against two human breast cancer cell lines (MCF-7, MDA-MB-231) in vitro by the MTT method. The evaluation results revealed that, in comparison with GA, compound 42 shows the most promising anticancer activity (IC50 1.88 ± 0.20 and 1.37 ± 0.18 µM for MCF-7 and MDA-MB-231, respectively) and merits further exploration as a new anticancer agent.

Synthesis and Biological Evaluation of Curcuminoid Derivatives.

Many curcuminoid derivatives have been reported to have multiple biological activities. The aim of this study was to improve the biological activity of curcuminoids by synthesizing 16 new derivatives which combined cinnamic acids with curcuminoids, and we also analyzed the structure-activity relationship of the new compounds. Almost all the new compounds showed encouraging activity, especially compound 7g. It had much better antioxidant activity than curcuminoids and Vitamin C (VC), and also had the most significant antibacterial activity, which was 5-folder better than ampicillin (one of the best marketed antibiotics) with a minimum inhibitory concentration (MIC) of 0.5 µg/mL against Gram-positive cocci (Staphylococcus aureus and Streptococcus viridans) as well as Escherichia coli and 0.6 µg/mL against Enterobacter cloacae. Compound 7g also showed the greatest anticancer activity with a much lower IC50, which was 0.51 µM against MCF-7, 0.58 µM against HepG-2, 0.63 µM against LX-2, and 0.79 µM against 3T3. The results suggest that these compounds have promising potential as candidates for the treatment of cancer and thus further studies are warranted.

[microRNA-203 INDUCING DIFFERENTIATION OF HUMAN EPIDERMAL STEM CELLS INTO SWEAT GLAND CELLS IN VITRO].

OBJECTIVE: To observe the possibility and mechanism of microRNA (miRNA)-203 inducing the human epidermal stem cells to differentiate into sweat gland cells. METHODS: Five normal human foreskin tissues were harvested to prepare a single cell suspension by 0.25% trypsin-EDTA digestion method, then the human epidermal stem cells were isolated and cultured by type IV collagen differential adherent method. The cell morphology was observed by inverted phase contrast microscope. The monoclonal antibodies of integrin ß1 (ITGB1), cytokeratin19 (CK19), CK1, CK10, CK18, and carcinoembryonic antigen (CEA) were used for identification by immunocytochemical staining. Double stranded mimics of has-miR-203 were transfected into the human epidermal stem cells with Lipofectamine 2000 (experimental group) and the human epidermal stem cells transfected with nonsense miRNA mimics served as control group. The monoclonal antibodies of ITGB1, CK19, CK1, CK10, CK18, and CEA were used for identifying the cells after transfection by immunocytochemical staining; the mRNA relative expressions of miRNA-203, P63, ITGB1, CK19, CK1, CK1O, CK18, and CEA were detected by real-time fluorescence quantitative RT-PCR before transfected and at 72 hours after transfected. The protein relative expressions of P63, ITGB1, CK19, CK1, CK10, CK18, and CEA were detected by Western blot. The mRNA expression of miRNA-203 and the mRNA and protein expressions of P63 were analyzed respectively with Pearson correlation. RESULTS: The CK19 and ITGB1 were positively expressed before transfection, but CK1, CK10, CK18, and CEA were expressed positively after transfection. The mRNA relative expression of miRNA-203 after transfection in experimental group was significantly higher than that before transfection (P < 0.05). The mRNA and protein relative expressions of CK1, CK10, CK18, and CEA after transfection in experimental group were significantly higher than those before transfection and control group (P < 0.05), while the mRNA and protein relative expressions of P63, CK19, and ITGB1 were significantly lower than those before transfection and control group (P < 0.05). These indicators showed no significant difference between the control group and before transfection (P > 0.05). The expression level of miRNA-203 was negatively correlated with the mRNA and protein relative expressions of P63 before and after transfection, the correlation coefficients before transfection were -0.91 (t = 3.862, P = 0.042) and -0.96 (t = 5.971, P = 0.009) respectively; the correlation coefficients after transfection were -0.92 (t = 4.283, P = 0.031) and -0.95 (t = 5.842, P = 0.011) respectively. CONCLUSION: miRNA-203 can induce epidermal stem cells to differentiate into sweat gland cells by targeting inhibition of P63 probably.

Differential microRNA expression profile comparison between epidermal stem cells and differentiated keratinocytes.

The aim of the current study was to analyze the differential microRNA (miRNA) expression profiles of human epidermal stem cells (ESCs) and differentiated keratinocytes. Enzyme digestion was used in combination with rapid adhesion to collagen IV to isolate primary human ESCs and differentiated keratinocytes, from which total RNA was extracted. Fluorescence labeling, microarray hybridization and differential expression analyses were performed. Reverse transcription quantitative polymerase chain reaction (RT­qPCR) was performed to validate the reliability of the microarray results and predict the target genes of the differentially expressed miRNAs. A total of 25 miRNAs, including hsa­miR­197­5p, hsa­miR­125b­5p and hsa­miR­376a­3p, were upregulated, whereas 166 miRNAs, including hsa­miR­29b­3p, hsa­miR­203 and hsa­miR­34a­3p, were downregulated in the human ESCs compared with the expression in differentiated keratinocytes. RT­qPCR results confirmed the upregulation of hsa­miR­197­5p and the downregulation of hsa­miR­29b­3p, which were consistent with the microarray results. miRNA target prediction indicated that the miRNA expression levels correlated with cell proliferation, differentiation, apoptosis and senescence. Expression levels of miRNAs significantly differed between human ESCs and differentiated keratinocytes. This finding may be attributed to their biological characteristics, such as proliferative behavior and differentiation abilities.

[Expression of microRNA-203 and P63 in human epidermal stem cells and keratinocytes].

OBJECTIVE: To observe the changes in expression of microRNA-203 and P63 in human epidermal stem cells and KCs, and to investigate their effects and significance in the epidermal proliferation and differentiation. METHODS: (1) Five normal foreskin tissue specimens were collected from 5 patients by circumcision in Department of Urinary Surgery of the First Affiliated Hospital of Nanchang University from March to June in 2013. Then single cell suspension was obtained by separating epidermis with trypsin digestion method. The cells were divided into quick adherent cells and non-quick adherent cells by type IV collagen differential adherent method. The biological characteristics of cells were observed by inverted phase contrast microscope immediately after isolation and on post culture day (PCD) 3. The expression of CD29, keratin 19, keratin 1, and keratin 10 was identified by immunocytochemical staining. The expression of microRNA-203 and mRNA of P63 was determined by real-time fluorescent quantitative RT-PCR. The protein expression of P63 was determined by Western blotting. Data were processed with t test and Pearson correlation analysis. RESULTS: (1) Immediately after isolation, quick adherent cells were small, round, and dispersed uniformly. On PCD 3, the cells adhered firmly, and they grew in clones. Immediately after isolation, non-quick adherent cells appeared in different shapes and sizes, and dispersed unevenly. On PCD 3, the cells adhered precariously and did not show clonal growth. Quick adherent cells showed positive expression of CD29 and keratin 19, while non-quick adherent cells showed positive expression of keratin 1 and keratin 10. Quick adherent cells were identified as epidermal stem cells, and non-quick adherent cells were identified as KCs. (2)The expression level of microRNA-203 in epidermal stem cells (0.74 ± 0.20) was lower than that in KCs (3.66 ± 0.34, t =16.582, P <0.001). The mRNA expression level of P63 in epidermal stem cells (4. 16 ± 0.28) was higher than that in KCs (2.90 ± 0.39, t =5. 850, P =0.001). The protein expression level of P63 in epidermal stem cells (1.42 ± 0.05) was higher than that in KCs (0.73 ± 0.03, t =26.460, P <0. 001). (3) The expression level of microRNA-203 was in significantly negative correlation with the expression levels of mRNA and protein of P63 (with r values respectively - 0. 94 and -0.98 , P values below 0.05). CONCLUSIONS: The expression levels of microRNA-203 and P63 in human epidermal stem cells and KCs were significantly different, which might be related to the different characteristics of proliferation and differentiation of the cells.

Synthesis and biological evaluation of novel curcuminoid derivatives.

Curcuminoids have been reported to possess multiple bioactivities, such as antioxidant, anticancer and anti-inflammatory properties. Three novel series of curcuminoid derivatives (11a-h, 15a-h and 19a-d) with enhanced bioactivity have been synthesized. Among the synthesized compounds, 11b exhibited the most significant activity with an MIC of 0.5 µM /mL against selected medically important Gram-positive cocci (S. aureus and S. viridans) and Gram-negative bacilli (E. coli and E. cloacae). The derivatives exhibited remarkable results in an antioxidant test with an IC50 2.4- to 9.3-folder smaller than curcuminoids. With respect to antiproliferative activity against Hep-G2, LX-2, SMMC7221 and MDA-MB-231, the derivatives exhibited an effect stronger than curcuminoids with an IC50 ranging from 0.18 to 4.25 µM.

[ROLE OF microRNA IN SKIN DEVELOPMENT AND WOUND HEALING].

OBJECTIVE: To review the role of microRNA (miRNA) in skin development and wound healing. METHODS: The recent literature about miRNA in skin development and wound healing was reviewed and analyzed. RESULTS: miRNA extensively involved in the development of the skin, including epidermal cell proliferation, differentiation, aging and hair follicle development; miR-203 known as the "skin-specific miRNA" can directly inhibit the expression of p63 and promote the differentiation of the epidermis. Meanwhile, miRNA also involved in various stages of skin regeneration and wound healing. Abnormal expression of miRNA is closely related with abnormal wound healing. CONCLUSION: miRNA play an important role in maintaining normal skin physiology and skin regeneration. To explore their roles in the healing of skin wounds and their regulatory mechanism can provide a new target for the treatment, which has a potential value and broad prospects.

[Quality of life of inpatients with coal workers' pneumoconiosis and its influential factors].

OBJECTIVE: To investigate the quality of life ( QOL) of inpatients with coal workers' pneumoconiosis( CWP) and analyse its influential factors, and to provide a theoretical basis for effective control measures. METHODS: Eighty-eight CWP patients in a hospital were included in the study. A questionnaire survey was conducted in them using a self-designed QOL scale. A database was established by software EpiData3.1, and the obtained data were statistically analyzed by software SPSS 16.0. RESULTS: Of the 88 patients, 73( 82.9%) had middle-level QOL, with a mean QOL loss rate of 36.2%; the loss rates of physical function and somatic sensation were the highest ( 44.2% and 41.5%). The patients with stage II CWP had significantly lower physical function than those with stage I and III CWP; the physical function and social function of patients significantly decreased with age; the personal income, household income, and housing condition of the patients had a marked impact on their physical and psychological functions, and the housing condition and education level had a marked impact on their social function. The multivariate analysis showed that old age, low income,and poor housing condition were the main adverse factors for the QOL of inpatients with CWP. CONCLUSION: The QOL of inpatients with CWP declines significantly, and their QOL is related to the age, income, and satisfaction with housing condition.

Study of Astragalus mongholicus polysaccharides on endothelial cells permeability induced by HMGB1.

Astragalus mongholicus polysaccharide (APS) shows various biological activities. Here, we explored the effect of APS on high mobility group protein 1 (HMGB1) -induced endothelial cell permeability. The results indicated APS pretreatment effectively inhibited HMGB1-induced increased permeability in endothelial cells (ECs). Signal transduction studies showed APS inhibited not only the activation of small guanylate Rho and its downstream effector Rho kinase (ROCK), but also the subsequent phosphorylation of myosin light chain (MLC) in ECs. In conclusion, our investigations suggested that APS inhibited HMGB1-induced increased permeability in ECs, regulated by Rho/ROCK signal pathways.

[Annexin A5 gene polymorphism (-1C/T) and the susceptibility to pneumoconiosis in coal works].

OBJECTIVE: To explore the role of -1C/T single nucleotide polymorphism within Annexin A5 gene in the genetic susceptibility to coal worker's pneumoconiosis (CWP). METHODS: Four hundred and seventy CWP Han chinese patients and 428 Han chinese controls were enclosed in present case-control study. All subjects were exposed to coal dusts. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the -1C/T SNP in Annexin A5 gene for all subjects. The relationship between the -1C/T SNP in Annexin A5 gene and CWP was analyzed. RESULTS: CT/TT genotype in -1C/T SNP was associated with a significantly decreased risk of CWP, as compared with the CC genotype among subgroups exposed to coal dusts for ≥ 27 years (adjusted OR = 0.65, 95%CI: 0.44 - 0.98, P = 0.039) and patients with CWP at stage II (adjusted OR = 0.55, 95%CI: 0.34 - 0.90, P = 0.028). CONCLUSION: The results of present study suggest that the Annexin A5 -1C/T polymorphism may be involved in the development of CWP in Han Chinese coal miners.

Associations of IL-4, IL-4R, and IL-13 gene polymorphisms in coal workers' pneumoconiosis in China: a case-control study.

BACKGROUND: The IL-4, IL-4 receptor (IL4R), and IL-13 genes are crucial immune factors and may influence the course of various diseases. In the present study, we investigated the association between the potential functional polymorphisms in IL-4, IL-4R, and IL-13 and coal workers' pneumoconiosis (CWP) risk in a Chinese population. METHODS: Six polymorphisms (C-590T in IL-4, Ile50Val, Ser478Pro, and Gln551Arg in IL-4R, C-1055T and Arg130Gln in IL-13) were genotyped and analyzed in a case-control study of 556 CWP and 541 control subjects. RESULTS: Our results revealed that the IL-4 CT/CC genotypes were associated with a significantly decreased risk of CWP (odds ratio (OR) = 0.74, 95% confidence interval (CI) = 0.58-0.95), compared with the TT genotype, particularly among subgroups of age <65 years (OR = 0.68, 95%CI = 0.46-0.99) and dust exposure years ≥26 years (OR = 0.69, 95%CI = 0.50-0.94). Moreover, the polymorphism was significantly associated with risk of CWP patients with stage I. In addition, a combined effect was observed in a dose-dependent manner with increasing numbers of risk variant alleles (P(trend) = 0.023), and individuals with 11-12 risk alleles had a 47% higher risk of CWP than those with 0-8 risk alleles (OR = 1.47, 95% CI = 1.05-2.05). CONCLUSIONS: Our results suggest that the IL-4 C-590T polymorphism is involved in the etiology of CWP and susceptibility to this disease. Larger studies are warranted to validate our findings.

[Analysis on the incidence of coal workers' pneumoconiosis from 2003 to 2008 in a coal mining group].

OBJECTIVE: Analyzed associations among the incidence of coal workers' pneumoconiosis from 2003 to 2008, jobs, exposure years and cumulative total dust exposure levels (CTE) and found the current characteristics of the mine incidence of pneumoconiosis disease. METHODS: collected the health care information of the new diagnosed pneumoconiosis of underground mine workers from 2003 to 2008 and the dust monitoring data of underground mine from 1949 and estimated the personnel cumulative total dust exposure levels (CTE); analyzed the incidence features of the new diagnosed pneumoconiosis. RESULTS: The rates of health surveillance of workers were gradually improved from 2003 to 2008 and 296 new coal workers pneumoconiosis were diagnosed. The total incidence was 0.57%, and the average annual rate was 0.32%. Among the new diagnosed cases, phase I accounted for 90.5% and the 87.2% from coal mine drillers. The shortest exposure period was 3 years and the longest was 38 years, and the cumulative total dose of dust was varied between 86.1 and 4926 mg/m(3) per year. The total dust accumulated limited dose was calculated by the percentile method to prevent 99% of miners from pneumoconiosis, which was 120.6 mg/m(3) per year, so we suggested that the exposure years should be shorter than 13 years under the current working conditions. CONCLUSIONS: Preventive coal workers' pneumoconiosis should be focused on mine drillers and their limited exposure years should be within 13 years.

[Polymorphisms in Fas pathway genes and risk of coal worker pneumoconiosis].

OBJECTIVE: To explore the possible association between six single nucleotide polymorphisms (SNPs) of Fas pathway genes and the risks of coal worker pneumoconiosis (GWP). METHODS: This case-control study consisted of 511 male patients with CWP and 530 male controls from the same coal mines. Five SNPs of Fas pathway genes were detected by restriction fragment length polymorphisms (PCR-RFLP) and CASP3 (rs6948) was genotyped by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: There were no differences of genotype frequencies of 6 SNPs between cases with CWP and controls. A significant increased risk of CWP was found in subjects with CASP8-652DD genotype as compared to subjects with CASP8-652II genotype (P < 0.05), and the further stratification analysis showed that smoking cases with CWP stage I, long exposure time and CASP8-652DD genotype had high risk of CWP (P < 0.05). The analysis of gene-gene interactions indicated that the carriers with FAS-1377GG/CASP8-652DD, FAS-670AG/CASP8-652DD and FASL-844CT/CASP8-652DD had the increased risk of CWP, and the carriers with FAS-1377GA/CASP8-652ID had the reduced risk of CWP. There were no significant differences of exposure times among the cases with CWP stage I and 3 genotypes of CASP8-652. CONCLUSION: CASP8-652 6N DD genotype may play a role in CWP development and interact with SNPs of FAS-1377, FAS-670 and FASL-844.

Common genetic variants in pre-microRNAs are associated with risk of coal workers' pneumoconiosis.

microRNAs (miRNAs) are an abundant class of small noncoding RNA molecules thought to be involved in biological functions, including embryonic development, chromosome architecture, cell proliferation and apoptosis. We hypothesized that common variants in the miRNAs are associated with risk of coal workers' pneumoconiosis (CWP). In a case-control study of 496 CWP patients and 513 control subjects frequency matched by exposure years and work types, we genotyped four single-nucleotide polymorphisms (SNPs) (rs2910164, rs2292832, rs11614913 and rs3746444) in pre-miRNAs (miR-146a, miR-149, miR-196a2 and miR-499) and assessed the associations with risk of CWP. A significantly increased risk of CWP was found for the miR-149 rs2292832 TT genotype (odds ratio (OR), 1.31; 95% confidence interval (CI), 1.01-1.69), compared with the CT/CC genotypes, and this increased risk was evident among subgroups of those aged > or =68 years (OR=1.52, 95% CI=1.03-2.25), dust exposure > or =26 years (OR=1.42, 95% CI=1.04-1.93) and ever smokers (OR=1.48, 95% CI=1.00-2.20). Furthermore, a significant association was observed between the genotypes and patients with stages II and III (OR=1.50, 95% CI=1.05-2.14 for stage II, and OR=3.33, 95% CI=1.67-6.65 for stage III). These results suggest that miR-149 rs2292832 polymorphism is involved in susceptibility to developing CWP.

Association of transforming growth factor-ß1 gene variants with risk of coal workers' pneumoconiosis.

OBJECTIVE: The aim of this case-control study was to explore whether five tagging single nucleotide polymorphisms (tSNPs) within the transforming growth factor-ß1 (TGF-ß1) gene were involved in manifestation of inflammatory and fibrotic processes associated with coal workers' pneumoconiosis (CWP). METHODS: The study included 508 CWP patients and 526 controls who were underground coal miners from Xuzhou Mining Business Group. Five tSNPs were selected from the HapMap and detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: The single SNP analysis showed that the genotype frequencies of SNP2 (rs1800470, +869T/C, extron 1) and SNP5 (rs11466345, intron 5) in CWP cases were significantly different from those in controls. Multivariate logistic regression analysis revealed that SNP2 (rs1800470) CC genotype was associated with decreased risk of CWP (OR = 0.50, 95% CI = 0.32-0.78), which was evident among subgroups of those never smoke (OR = 0.40, 95%CI = 0.24-0.66), cases with stage II (OR = 0.41, 95%CI = 0.22-0.76) and exposure period (< 28 y: OR = 0.54, 95%CI = 0.31-0.95; ≥28 y: OR = 0.52, 95%CI = 0.32-0.96). However, the SNP5 (rs11466345) GG genotype was associated with an increased risk of CWP (OR = 2.5, 95%CI = 1.36-4.57), and further stratification analysis showed that the risk of CWP was increased in both smoking and nonsmoking groups, shorter and longer exposure groups, while the risk of CWP was only increased in patients with stage I and II. CONCLUSION: This study suggests that TGF-ß1 polymorphisms may contribute to susceptibility of CWP.