Modified traditional TNM staging of pyriform sinus and hypopharyngeal and laryngeal cancer based on lymph node ratio and its clinical significance: a population-based study combined with external validation.

BACKGROUND: To evaluate the application value of a new TLNRM staging prediction model based on lymph node ratio (LNR) in patients with Pyriform Sinus and Hypopharyngeal and Laryngeal cancer (PHLC). METHODS: A total of 2,257 patients with pathologically diagnosed PHLC from 2004 through 2019 were collected from the SEE database for analysis. The N staging of AJCC was replaced by LNR, and we compared the differences in patient prognosis and judgment ability between the new TLNRM staging and the 8th edition TNM staging. At the same time, data from 1,094 people in our hospital were included for external verification and validation. RESULTS: We selected four cutoff points based on LNR and reclassified N staging into five groups (LNR1-5). Compared to the traditional TNM staging (8th edition), the new TLNRM staging showed a statistically significant 5-year OS difference. The decision curve showed that the new TLNRM staging had a higher net benefit for different decision thresholds than the traditional TNM staging system's prediction line. The smaller AIC and BIC suggested that the new staging system had a higher sensitivity to prognosis evaluation compared to the traditional staging system. TLNRM stage III patients can benefit from radiotherapy, while TLNRM IVA and IVB patients can benefit from chemoradiotherapy. The same conclusion has been drawn from external validation data from our center. CONCLUSIONS: Compared with the traditional 8th edition AJCC staging system, the new TLNRM staging system has advantages in predicting the staging and prognosis of PHLC patients, and can independently guide postoperative chemoradiotherapy in patients.

Obesity-related glomerulopathy: recent advances in inflammatory mechanisms and related treatments.

Obesity-related glomerulopathy, which is an obesity-triggered kidney damage, has become a significant threat to human health. Several studies have recently highlighted the critical role of inflammation in obesity-related glomerulopathy development. Additionally, excess adipose tissue and adipocytes in patients with obesity produce various inflammatory factors that cause systemic low-grade inflammation with consequent damage to vascular endothelial cells, exacerbating glomerular injury. Therefore, we conducted a comprehensive review of obesity-related glomerulopathy and addressed the critical role of obesity-induced chronic inflammation in obesity-related glomerulopathy pathogenesis and progression, which leads to tubular damage and proteinuria, ultimately impairing renal function. The relationship between obesity and obesity-related glomerulopathy is facilitated by a network of various inflammation-associated cells (including macrophages, lymphocytes, and mast cells) and a series of inflammatory mediators (such as tumor necrosis factor α, interleukin 6, leptin, adiponectin, resistin, chemokines, adhesion molecules, and plasminogen activator inhibitor 1) and their inflammatory pathways. Furthermore, we discuss a recently discovered relationship between micronutrients and obesity-related glomerulopathy inflammation and the important role of micronutrients in the body's anti-inflammatory response. Therefore, assessing these inflammatory molecules and pathways will provide a strong theoretical basis for developing therapeutic strategies based on anti-inflammatory effects to prevent or delay the onset of kidney injury.

Association of serum Nrf2 protein levels with disease activity and renal impairment in lupus nephritis.

Introduction: We aimed to investigate the relationship between nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression levels, lupus nephritis (LN) disease activity, and the degree of renal injury (based on the estimated glomerular filtration rate [eGFR]) in patients with LN. Methods: We selected 40 healthy control participants and 102 patients with LN who were treated in the Second Hospital of Jilin University, China, for inclusion in this study. Patients with LN were classified into LN with high-eGFR and LN with low-eGFR groups. Nrf2 protein levels were measured in the serum and renal tissues of the participants in both groups to assess the correlation between Nrf2 protein levels and different LN disease states. Results: There was a significantly positive correlation between serum Nrf2 protein levels, the degree of renal injury, and systemic lupus erythematosus disease activity index (SLEDAI) scores in patients with LN. Nrf2 protein levels were higher in the LN with high-eGFR group than in the healthy control and LN with low-eGFR groups. In follow-up patients in the LN high eGFR group, Nrf2 protein levels decreased significantly after remission of disease activity. Conclusion: Nrf2 protein expression has a dual role in patients with LN. Nrf2 protein levels not only correlate with disease activity in patients with LN, but also with the degree of kidney injury. Before implementing targeted therapy for Nrf2, evaluating both Nrf2 protein expression and the disease state in patients with LN is necessary to better identify and place each patient in an appropriate patient group.

Immune-mediated inflammatory diseases and leukocyte telomere length: A Mendelian randomization study.

Objective: To elucidate the potential causality of leukocyte telomere length (LTL) with immune-mediated inflammatory diseases (IMIDs), we conducted a Mendelian randomization (MR) study. Methods: The genetically predicted causation between LTL and IMIDs was evaluated using a two-sample MR method. We analyzed 16 major IMIDs, which included systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), ulcerative colitis (UC), Crohn's disease (CD), ankylosing spondylitis (AS), sicca syndrome (SS), rheumatoid arthritis (RA), type 1 diabetes (T1D), primary sclerosing cholangitis (PSC), idiopathic pulmonary fibrosis (IPF), atopic dermatitis (AD), sarcoidosis, hypothyroidism, hyperthyroidism, psoriasis, and childhood asthma. The random-effects inverse-variance weighted (IVW) method was performed as the main analytical approach in MR. Various sensitivity analyses, including MR-Egger, MR robust adjusted profile score (MR-RAPS), weighted median, MR pleiotropy residual sum and outlier (MR-PRESSO) methods, weighted mode, radial plot, and radial regression, were used to guarantee the robustness of the results and detect horizontal pleiotropy. Cochran's Q value was calculated to check for heterogeneity, and the MR Steiger approach was used to test the causal direction. Results: The MR results indicated significant inverse associations of LTL with risks of psoriasis (OR: 0.77, 95% CI: 0.66-0.89, and p = 3.66 × 10-4), SS (OR: 0.75, CI: 0.58-0.98, and p = 0.03), RA (OR: 0.77, 95% CI: 0.68-0.88, and p = 9.85 × 10-5), hypothyroidism (OR: 0.84, 95% CI: 0.78-0.91, and p = 7,08 × 10-6), hyperthyroidism (OR: 0.60, 95% CI: 0.44-0.83, and p = 1.90 × 10-3), sarcoidosis (OR: 0.67, 95% CI: 0.54-0.83, and p = 2.60 × 10-4), and IPF (OR: 0.41, 95% CI: 0.29-0.58, and p = 4.11 × 10-7) in the FinnGen study. We observed that longer LTL was associated with an increased risk of AS susceptibility (OR: 1.51, 95% CI: 1.18-1.94, and p = 9.66 × 10-4). The results of the IVW method showed no causal relationship between TL and SLE (OR: 0.92, 95% CI: 0.62-1.38, and p = 0.69) in the FinnGen study; however, a significantly positive correlation was shown between LTL and SLE in another larger GWAS (OR: 1.87, 95% CI: 1.37-2.54, and p = 8.01 × 10-5). Conclusion: Our findings reveal that abnormal LTL has the potential to increase the risk of IMIDs. Therefore, it could be treated as a predictor and may provide new potential treatment targets for IMIDs. However, the change of LTL may not be the direct cause of IMIDs. Further studies should aim at the pathogenic mechanism or potential protective effects of LTL in IMIDs.

Profiles of novel high-molecular-weight synthetic antioxidants in urine and associated child exposure in China.

The aim of this study is to investigate the exposure of novel high-molecular-weight (HMW) synthetic antioxidants (AOs), including nine synthetic phenolic antioxidants (SPAs), one low-molecular-weight (LMW) SPA, two organophosphite antioxidants (OPAs) as well as one transformation product in children's urine from eastern (n = 82) and western (n = 105) China. For the first time, all analytes were detected in children's urine such as the representative HMW SPAs pentaerythritol tetrakis(3-(3,5-di-tert-butyl-4-hydroxyphenyl) propionate) (AO1010, median = 0.447 ng/mL), octadecyl-3-(3,5-di-tert-butyl-4-hydroxyphenyl) propionate (AO1076, median = 0.0300 ng/mL), and 1,3,5-tris[(3,5-di-tert-butyl-4-hydroxyphenyl)methyl]-1,3,5-triazinane-2,4,6-trione(1,2-dioxoethylene)bis(iminoethylene) (AO3114, median = 0.0166 ng/mL) and representative OPAs bis(2,4-di-tert-butylphenyl) pentaerythritol diphosphite (AO626, median = 0.00216 ng/mL), tris(2,4-di-tert-butylphenyl) phosphite (AO168, median = 0.0296 ng/mL) as well as its transformation product tris(2,4-di-tert-butylphenyl) phosphate (AO168O, median = 1.53 ng/mL). Significant differences were observed in the concentrations of AO1010, AO3114, AO168, and AO168O between urine samples from eastern and western China (p < 0.01). The high-frequency combination of AOs from binary to a mixture of six AOs was acquired, which would provide a better investigation of the mixture toxicity. The high estimated daily intakes of AO1010 (85.4 ng/kg/day), AO1076 (10.2 ng/kg/day), AO3114 (4.50 ng/kg/day), and AO168 (1231 ng/kg/day) were less than the values of the tolerable daily intake (3,020,000, 1,500,000, 10,000,000, and 580,000 ng/kg/day for AO1010, AO1076, AO3114, and AO168, respectively), indicating low health risk to children. Our findings showed the co-occurrence of those novel AOs and transformation products in children, the overall risks associated with the mixture of transformation products and the mixture with other emerging pollutants need to be considered when assessing the risks of AOs in further studies.

COVID-19 Pandemic Impacts on Humans Taking Antibiotics in China.

The outbreak of the novel coronavirus 2019 (COVID-19) pandemic has resulted in the increased human consumption of medicines. Antibiotics are of great concern due to their adverse effects, such as increased bacterial resistance and dysbiosis of gut microbiota. Nevertheless, very little is known about the changes in self-medication with antibiotics during the COVID-19 pandemic and the resultant potential health risks. Herein, we examined the concentration profiles of some commonly used antibiotics in human urine collected from several geographical regions in China between 2020 and 2021. Antibiotics were found in 99.2% of the urine samples at concentrations ranging from not detected (nd) to 357 000 (median: 10.2) ng/mL. During the COVID-19 pandemic, concentrations of urinary antibiotics were remarkably higher than those found either before the pandemic or in the smooth period of the pandemic. Moreover, elevated levels of antibiotics were determined in urine samples from the regions with more confirmed cases. The exposure assessment showed that hazard index values >1 were determined in 35.2% of people. These findings show that human exposure to antibiotics increased during the COVID-19 pandemic, and further research is imperative to identify the public health risks.

Co-exposure and health risks of several typical endocrine disrupting chemicals in general population in eastern China.

Human exposure to endocrine disrupting chemicals (EDCs) is a health concern due to their wide use and interference with the human endocrine system. Parabens, bisphenols, benzophenones, triclosan (TCC), triclocarban (TCS), and tetrabromobisphenol-A (TBBPA) and its derivatives tetrachlorobisphenol-A (TCBPA) and tetrabromobisphenol-S (TBBPS), are typical EDCs that are frequently detected in environmental and human samples. However, only a few studies have assessed the co-exposure of these chemicals in humans. In this study, urine samples were collected from the general population in the city of Wuxi (n = 121) and a county, Taishun (n = 120), eastern China, and analyzed for these EDCs. Parabens, bisphenols, TCS, and benzophenones were frequently detected in urine, whereas TBBPA and its derivatives were not detected. The geometric mean concentrations of parabens, bisphenols, and benzophenones in urine from the Wuxi population were 25.7, 2.45, and 2.34 ng/mL, respectively, which were substantially higher than those from the Taishun population (17.2, 1.70, and 2.65 ng/mL). These results suggest an urban-rural difference in urinary EDCs. The exposure risks to these EDCs were estimated based on the measured urinary concentrations and acceptable daily intakes (ADIs). Hazard quotient values for EDCs in humans from both locations were generally less than 1, indicating a low exposure risk of EDCs in these regions. Nonetheless, the health risks caused by co-exposure to such EDCs cannot be ignored.