Tertiary lymphoid structures generate and propagate anti-tumor antibody-producing plasma cells in renal cell cancer.

The presence of intratumoral tertiary lymphoid structures (TLS) is associated with positive clinical outcomes and responses to immunotherapy in cancer. Here, we used spatial transcriptomics to examine the nature of B cell responses within TLS in renal cell carcinoma (RCC). B cells were enriched in TLS, and therein, we could identify all B cell maturation stages toward plasma cell (PC) formation. B cell repertoire analysis revealed clonal diversification, selection, expansion in TLS, and the presence of fully mature clonotypes at distance. In TLS+ tumors, IgG- and IgA-producing PCs disseminated into the tumor beds along fibroblastic tracks. TLS+ tumors exhibited high frequencies of IgG-producing PCs and IgG-stained and apoptotic malignant cells, suggestive of anti-tumor effector activity. Therapeutic responses and progression-free survival correlated with IgG-stained tumor cells in RCC patients treated with immune checkpoint inhibitors. Thus, intratumoral TLS sustains B cell maturation and antibody production that is associated with response to immunotherapy, potentially via direct anti-tumor effects.

Circulating miR-125a but not miR-125b is decreased in active disease status and negatively correlates with disease severity as well as inflammatory cytokines in patients with Crohn's disease.

AIM: To determine the association of circulating miR-125a/b expression with the risk and disease severity of Crohn's disease (CD), and with inflammatory cytokines. METHODS: Plasma samples were collected from patients with active CD (A-CD), or CD in remission (R-CD) and from healthy controls (HCs). The levels of the inflammatory cytokines interleukin-17 (IL-17), tumour necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) were measured by enzyme-linked immunosorbent assay. The expression of miR-125a/b was assessed by quantitative polymerase chain reaction (qPCR). RESULTS: Twenty-nine A-CD patients, 37 R-CD patients, and 37 HCs were included in the study. Plasma miR-125a expression was decreased in A-CD patients compared with that in R-CD patients (P < 0.001) and HCs (P < 0.001). miR-125a expression levels enabled the differentiation of A-CD from R-CD patients [area under curve (AUC) = 0.854] and from HCs (AUC = 0.780), whereas miR-125b expression did not. miR-125a was negatively correlated with C-reaction protein (CRP) (P = 0.017), erythrocyte sedimentation rate (ESR) (P = 0.026), Crohn's disease activity index (CDAI) (P = 0.003), IL-17 (P = 0.015), and TNF-α (P = 0.004) in A-CD patients. Furthermore, miR-125a was negatively associated with CRP (P = 0.038) and CDAI (P = 0.021) in R-CD patients. Regarding miR-125b, no association with CRP, CDAI, IL-17, TNF-α, or IFN-γ was found in A-CD or in R-CD patients. miR-125a levels gradually increased in A-CD patients who achieved clinical remission (P = 0.009) after 3-mo treatment, whereas they remained unchanged among patients who failed to achieve remission. No changes in miR-125b expression were detected in remission or non-remission patients after treatment. CONCLUSION: Circulating miR-125a but not miR-125b is decreased in patients with active disease status and negatively correlates with disease severity and inflammatory cytokines in patients with CD.

Prevalence of dyslipidaemia and risk factors in Chinese coal miners: a cross-sectional survey study.

BACKGROUND: Although coal miners are susceptible to dyslipidaemia owing to their highly risky and stressful working environment as well as unhealthy lifestyle, very few studies have focused on this issue thus far. Therefore, this study investigated the current epidemiological characteristics of dyslipidaemia among Chinese coal miners. METHODS: Demographic, anthropometric, and biochemical data were gathered from 4341 coal miners in China. Dyslipidaemia was diagnosed based on the serum lipid levels. Univariate and multivariate logistic regression analyses were used to assess the related risk factors for dyslipidaemia. RESULTS: The average concentrations of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were 5.01 ± 0.93 mmol/L, 1.90 ± 1.72 mmol/L, 1.21 ± 0.35 mmol/L, and 3.15 ± 0.80 mmol/L, respectively. Additionally, 38.08% of participants had a high TC level, 25.84% had a low HDL-C level, 35.08% had a high LDL-C level, and 40.46% had a high TG level. The overall prevalence of dyslipidaemia was 68.28% (95% CI: 66.90-69.66%). Factors associated with dyslipidaemia were age, sex, marital status, monthly family income, type of work, length of service, smoking status, smoking index, drinking status, alcohol consumption per day, elevated fasting glucose, hypertension, obesity and abdominal obesity. CONCLUSIONS: Our study's results indicated a very high prevalence of dyslipidaemia among Chinese coal miners and identified various risk factors for dyslipidaemia.

Relationship Between Physical Activity Patterns and Metabolic Syndrome Among Male Coal Miners of Shanxi Province in China.

OBJECTIVE: This study aimed to investigate the relationship between metabolic syndrome (MetS) and physical activity (PA) in different domains among male coal miners of Shanxi Province in China. METHOD: The study was conducted from July 2013 to December 2013. A two-stage stratified cluster sampling method was used. Data regarding the general information of participants were collected by well-trained interviewers. MetS was defined according to IDF criteria. Self-reported PA was obtained with the IPAQ and categorized into three tertiles of intensity levels across occupation, transportation, household, and leisure-time domains. Univariate and multiple logistic regression analysis were applied to compute the odds ratios and their 95% confidence interval (CI). RESULTS: A total of 3076 males aged 18-65 years old were recruited in this cross-sectional study. The prevalence of MetS was 40.5% in the study subjects. The percentages of vigorous-intensity PA in MetS and non-MetS groups were 70.07% and 62.92%, respectively. Participants spent most of their time on occupation (2034 MET-min/w) and transportation (693MET-min/w) domains. Higher-intensity levels in occupation domains were significantly associated with lower risk of MetS (OR: 0.759, 95% CI: 0.633-0.911; OR: 0.627, 95% CI: 0.516-0.762). CONCLUSIONS: Across four types of workers, the relationships between PA domains and MetS were different. For underground and underground auxiliary workers, the negative relationship was found between occupation PA and MetS. For office workers, the negative relationship was found between household PA and MetS. For ground workers, only leisure-time PA had positively related to MetS.