Background Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with the development of metabolic syndrome (MS). However, the role of amino acids in PAH-induced MS remains unclear. Objective To explore the impact of PAHs exposure on the incidence of MS among coking workers, and to determine potential modifying effect of amino acid on this relationship. Methods Unmatched nested case-control design was adopted and the baseline surveys of coking workers were conducted in two plants in Taiyuan in 2017 and 2019, followed by a 4-year follow-up. The cohort comprised 667 coking workers. A total of 362 participants were included in the study, with 84 newly diagnosed cases of MS identified as the case group and 278 as the control group. Urinary levels of 11 PAH metabolites and plasma levels of 17 amino acids were measured by ultrasensitive performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Logistic regression was used to estimate the association between individual PAH metabolites and MS. Stratified by the median concentration of amino acids, Bayesian kernel machine regression (BKMR) model was employed to assess the mixed effects of PAHs on MS. Due to the skewed data distribution, all PAH metabolites and amino acids in the analysis were converted by natural logarithm ln (expressed as lnv). Results The median age of the 362 participants was 37 years, and 83.2% were male. Compared to the control group, the case group exhibited higher concentrations of urinary 2-hydroxyphenanthrene (2-OHPhe), 9-hydroxyphenanthrene (9-OHPhe), and hydroxyphenanthrene (OHPhe) (P=0.005, P=0.049, and P=0.004, respectively), as well as elevated levels of plasma branched chain amino acid (BCAA) and aromatic amino acid (AAA) (P<0.05). After being adjusted for confounding factors, for every unit increase in lnv_2-OHPhe in urine, the OR (95%CI) of MS was 1.57 (1.11, 2.26), and for every unit increase in lnv_OHPhe, the OR (95%CI) of MS was 1.82 (1.16, 2.90). Tyrosine, leucine, and AAA all presented a significant nonlinear correlation with MS. At low levels, tyrosine, leucine, and AAA did not significantly increase the risk of MS, but at high levels, they increased the risk of MS. In the low amino acid concentration group, as well as in the low BCAA and low AAA concentration groups, it was found that compared to the PAH metabolite levels at the 50th percentile (P₅₀), the log-odds of MS when the PAH metabolite levels was at the 75th percentile (P₇₅) were 0.158 (95%CI: 0.150, 0.166), 0.218 (95%CI: 0.209, 0.227), and 0.262 (95% CI: 0.241, 0.282), respectively, However, no correlation between PAHs and MS was found in the high amino acid concentration group. Conclusion Amino acids modify the effect of PAHs exposure on the incidence of MS. In individuals with low plasma amino acid levels, the risk of developing MS increases with higher concentrations of mixed PAH exposure. This effect is partly due to the low concentrations of BCAA and AAA.

BACKGROUND: It is inaccurate to reflect the level of dust exposure through working years. Furthermore, identifying a predictive indicator for lung function decline is significant for coal miners. The study aimed to explored whether club cell secretory protein (CC16) levels can reflect early lung function changes. METHODS: The cumulative respiratory dust exposure (CDE) levels of 1,461 coal miners were retrospectively assessed by constructed a job-exposure matrix to replace working years. Important factors affecting lung function and CC16 were selected by establishing random forest models. Subsequently, the potential of CC16 to reflect lung injury was explored from multiple perspectives. First, restricted cubic spline (RCS) models were used to compare the trends of changes in lung function indicators and plasma CC16 levels after dust exposure. Then mediating analysis was performed to investigate the role of CC16 in the association between dust exposure and lung function decline. Finally, the association between baseline CC16 levels and follow-up lung function was explored. RESULTS: The median CDE were 35.13 mg/m³-years. RCS models revealed a rapid decline in forced vital capacity (FVC), forced expiratory volume in the first second (FEV₁), and their percentages of predicted values when CDE exceeded 25 mg/m³-years. The dust exposure level (<5 mg/m³-years) causing significant changes in CC16 was much lower than the level (25 mg/m³-years) that caused changes in lung function indicators. CC16 mediated 11.1% to 26.0% of dust-related lung function decline. Additionally, workers with low baseline CC16 levels experienced greater reductions in lung function in the future. CONCLUSIONS CC16 levels are more sensitive than lung indicators in reflecting early lung function injury and plays mediating role in lung function decline induced by dust exposure. Low baseline CC16 levels predict poor future lung function.
Uteroglobin/blood* ; Humans ; Dust/analysis* ; Occupational Exposure/analysis* ; Male ; Middle Aged ; Adult ; Retrospective Studies ; Lung Injury/chemically induced* ; Coal Mining ; Biomarkers/blood* ; China/epidemiology* ; Air Pollutants, Occupational ; Female

Objective To analyze the effects of Porphyromonas gingivalis(Pg)infection and expression of vitamin D pathway-related proteins on the survival and prognosis of patients with esophageal squamous cell carcinoma(ES-CC).Methods Pg infection and the expression of 24 hydroxylase(CYP24A1),1α hydroxylase(CYP27B1)and vitamin D receptor(VDR)in 173 ESCC tissues were detected by immunohistochemistry.The correlation between each index and the survival time of patients was analyzed.Results The positive rates of Pg,CYP24A1,CYP27B1 and VDR in ESCC were 43.35％,37.57％,20.23％and 21.97％,respectively.The 5-year survival time of ES-CC patients in the Pg+CYP24A1+CYP27B-VDR-high-risk group was shortened(P＜0.05).Conclusion Pg infection and vitamin D pathway-associated proteins can be used as reliable indicators to predict the survival and prognosis of ESCC patients.

Objective: To investigate the effect of Porphyromonas gingivallis ( Pg) infection of esophageal cancer cells on the polarization of tumor associated macrophages (TAMs) and functional changes. Methods: The secretion of tumor⁃related cytokines in the supernatant of Pg infected and uninfected esophageal squamous cell carcinoma (ESCC) cells was detected by ELISA. A co⁃culture model of ESCC cells and macrophages in vitro was established ,and the changes of TAMs surface markers were detected by qPCR , cellular immunofluorescence and flow cytometry. Cytokines secreted by TAMs after co⁃culture were detected by ELISA. ESCC cells were cultured using conditioned medium of co⁃cultured TAMs , and the effects of TAMs on the proliferation , migration and invasion of esophageal cancer cells were evaluated by CCK⁃8 , Wound⁃healing assay and Transwell assay. Results: The expression quantity of IL⁃6 and IL⁃10 of Pg⁃infected ESCC cells increased (P < 0. 01) . The contents of CD163 and CD206 on the surface of TAMs co⁃cultured with Pg⁃infected ESCC cells increased (P < 0. 001) . The cytokines IL⁃6 and IL⁃10 secreted by TAMs co⁃cultured with Pg⁃infected ESCC cells relatively increased (P < 0. 01) . TAMs co⁃cultured with Pginfected ESCC cells were able to enhance ESCC cells proliferation , migration and invasion (all P < 0. 05) . Conclusion Pg infection of ESCC cells can induce the secretion of cytokines , remodel TAMs to polarize toward the M2type immunosuppressive phenotype , thereby promoting the malignant biological behavior of ESCC cells. This study provides data support for the etiology of esophageal cancer and potential target molecules for clinical immunotherapy targeting TAMs.

Objective : To explore the relationship between Porphyromonas gingivalis(Pg) and mitophagy in esopha- geal cancer cells，and to explore new therapeutic targets for esophageal cancer． Methods : ① Western blot was used to detect the phosphorylation of unc-51-like authophagy activating kinase1 (ULK1) in mitochondria of the Pg infected cells and immunohistochemical method was used to detect the correlation between the expression of Pg and the phosphorylation status of ULK1 in esophageal cancer tissues. ② Western blot，ICC and ELISA were used to de- tect the transfer of nucleotide blinding domain and leucine rich repeat containing family member X1 (NLRX1) from cytoplasm to mitochondria，mitophagy，and the secretion levels of interleukin ( IL) -6 and reactive oxygen species (ROS) under Pg infection. ③ Pg colonization in esophageal tissues of mice in each group was detected by qPCR and Pg colonization in esophageal squamous epithelial cells of mice by RNAscope. Results : Compared with the un- treated group，the phosphorylation level of mitochondrial ULK1 (P＜0．01) ，NLRX1 expression (P＜0. 001) and mitophagy (P＜0. 001) of esophageal cancer cells increased after Pg infection．Compared with the control group， the combined intervention group could inhibit Pg colonization in esophageal tissue and esophageal squamous epithe- lial cells of mice (P＜0. 001) ． Conclusion Pg promotes the translocation of NLRX1 from cytoplasm to mitochon- dria by up-regulating the phosphorylation level of ULK1 in the mitochondria of esophageal cancer cells，and then induces mitophagy，leading to the reduction secretion of IL-6 and ROS，and ultimately maintaining Pg colonization.

Objective:This study aimed to investigate the associations between single-nucleotide polymorphism (SNP) of IGF-1 and IGFBP-3 gene and risk of non-smoking female lung cancer in Chinese population. Methods:Genotyping was performed using the TaqMan method in 287 histologically confirmed non-smoking female lung cancer cases and 281 healthy controls. Results:The geno-type distributions of IGF-1 polymorphisms were significantly different between cases and controls (P<0.001). Analysis of multivariate logistic regression showed that the carriers of the CC genotype exhibited a significantly decreased risk of lung cancer in non-smoking female (adjusted OR=0.28, 95%CI:0.15-0.54). IGF-1 rs1520220 GG genotype may reduce the risk of advanced lung cancer incidence in nonsmoking female (adjusted OR=0.30, 95%CI:0.09-0.96). Log-rank test and Cox regression analyses revealed that variant geno-types of IGF-1 rs2946834 CT/TT had a significantly decreased lung cancer mortality risk compared with the homozygote CC in≥60 age group or patients with a lung tumor>3 cm. Conclusion:The IGF-1 polymorphism was associated with the risk of lung cancer and prognosis among non-smoking female. More rigorous laboratory studies of large sample population and functional studies are warrant-ed to confirm our findings.

BACKGROUNDNowadays, there are published trials in regards to the comparison of caspofungin with liposomal amphotericin B (L-AmB). However, these studies have a modest sample size and convey inconclusive results. The aim of this study was to review the efficacy and safety of caspofungin for the treatment of invasive fungal infections (IFIs), compared with L-AmB.

METHODSElectronic databases (up to July 31, 2013) PubMed and Embase databases, the Cochrane Library, and Google Scholar were searched to identify relevant trials of caspofungin and L-AmB. Analyses of efficacy and adverse outcomes were performed by relative risks (RRs) and 95% confidence intervals (CIs). Heterogeneity was assessed by χ(2)-test and the I(2)-statistic.

RESULTSThree trials were included in this meta-analysis with 1249 modified intention-to-treat (MITT) patients. The results showed that caspofungin produced equal efficacy in favorable overall response (RR = 1.02, 95% CI 0.88-1.18; P = 0.81) and mortality rate (RR = 1.53, 95% CI 0.38-6.27, P = 0.55), safer in clinical adverse events (RR = 0.20, 95% CI 0.08-0.54; P = 0.001), laboratory adverse events (RR = 0.69, 95% CI 0. 57-0.84; P = 0.0002), and discontinuation rate (RR = 0.26, 95% CI 0.08-0.83, P = 0.02), compared with L-AmB in the treatment of patients with IFIs.

CONCLUSIONBased on the results of this meta-analysis, it would appear that caspofungin was measured to have equal efficacy in clinical outcomes and safer in terms of adverse events.

Amphotericin B ; therapeutic use ; Antifungal Agents ; therapeutic use ; Echinocandins ; therapeutic use ; Febrile Neutropenia ; drug therapy ; Humans ; Lipopeptides ; Mycoses ; drug therapy

3' Untranslated Regions ; Animals ; Biomarkers ; metabolism ; Cell Proliferation ; Cell Survival ; Embryonic Stem Cells ; cytology ; metabolism ; Induced Pluripotent Stem Cells ; cytology ; metabolism ; Mice ; Swine ; Transcription Factors ; genetics ; metabolism