Tri-ortho-cresyl phosphate induces hepatic steatosis by mTOR activation and ER stress induction.

Tri-ortho-cresyl phosphate (TOCP), an organophosphorus compound (OP), which is widely used as plasticizer, flame retardant and other industrial products, has been reported to cause multiple toxicities including neurotoxicity and reproductive toxicity. However, it remains to be elusive whether TOCP induces hepatotoxicity. The purpose of this study was to investigate the effect of TOCP on hepatocytes and the lipid metabolism in particular. The adult mice were given a single dose of TOCP (800 mg/kg, p.o.) and the histological changes in liver tissue and lipid content in serum were determined. The results showed that more vacuoles and lipid droplets were observed in the liver of the mice exposed to TOCP. And triglyceride concentrations in serum and liver tissue significantly increased. However, the histopathological changes of the liver and the elevated triglyceride levels in the exposed mice can be reversed by endoplasmic reticulum (ER) stress inhibitor 4-phenylbutyric acid and mTOR signal inhibitor rapamycin. It was also found that the changes of expression levels of the biomarkers of ER stress and mTOR signaling pathway, such as GRP78, CHOP, and p-mTOR, in the exposed mice were consistent with those observed in the cultured primary hepatocytes treated with the same chemicals. These results showed that TOCP activated mTOR signal and ER stress to induce de novo lipid synthesis, which led to the hepatic steatosis in mouse.

Immediate Ansa cervicalis-to-recurrent laryngeal nerve low-tension anastomosis: A new technique for phonation recovery and bilateral anastomoses to avoid tracheotomy.

OBJECTIVE: This case series study investigated the outcomes of an innovative approach, ansa cervicalis nerve (ACN)-to-recurrent laryngeal nerve (RLN) low-tension anastomosis. METHODS: Patients who received laryngeal nerve anastomosis between May 2015 and September 2021 at the facility were enrolled. The inclusion criteria were patients with RLN dissection and anastomosis immediately during thyroid surgery. Exclusion criteria were cases with anastomosis other than cervical loop-RLN anastomosis or pronunciation recovery time > 6 months. Patients admitted before January 2020 were assigned to group A which underwent the conventional tension-free anastomosis, and patients admitted after January 2020 were group B and underwent the innovative low-tension anastomosis (Dong's method). RESULTS: A total of 13 patients were included, 11 patients received unilateral surgery, and 2 underwent bilateral surgery. For patients who underwent unilateral anastomosis, group B had a significantly higher percentage of normal pronunciation via GRBAS scale (83.3 % vs. 0 %, p = 0.015) and voice handicap index (66.7 % vs. 0 %, p = 0.002), and shorter recovery time in pronunciation (median: 1-day vs. 4 months, p = 0.001) than those in group A after surgery. CONCLUSIONS: ACNs-to-RLN low-tension anastomosis with a laryngeal segment ≤1 cm (Dong's method) significantly improves postoperative pronunciation and recovery time. The results provide clinicians with a new strategy for ACN -to-RLN anastomosis during thyroid surgery.

Metabolomic analysis of the serum and urine of rats exposed to diazinon, dimethoate, and cypermethrin alone or in combination.

BACKGROUND: Multiple pesticides are often used in combination for plant protection and public health. Therefore, it is important to analyze the physiological changes induced by multiple pesticides exposure. The objective of this study was to investigate the combined toxicity of the widely-used organophosphorus and pyrethroid pesticides diazinon, dimethoate, and cypermethrin. METHODS: Male Wistar rats were administrated by gavage once daily with the three pesticides individual or in combination for consecutive 28 days. The metabolic components of serum and urine samples were detected by using 1H nuclear magnetic resonance (NMR)-based metabolomics method. Histopathological examination of liver and kidneys and serum biochemical determination were also carried out. RESULTS: The results showed that after the 28-day subacute exposure, serum glutamic transaminase and albumin were significantly increased and blood urea nitrogen was significantly decreased in the rats exposed to the mixture of the pesticides compared with the control rats, suggesting that the co-exposure impaired liver and kidney function. Metabolomics analysis indicated that the indicators 14 metabolites were statistically significant altered in the rats after the exposure of the pesticides. The increase in 3-hydroxybutyric acid in urine or decrease of lactate and N-acetyl-L-cysteine in serum could be a potentially sensitive biomarker of the subchronic combined effects of the three insecticides. The reduction level of 2-oxoglutarate and creatinine in urine may be indicative of dysfunction of liver and kidneys. CONCLUSION: In summary, the exposure of rats to pesticides diazinon, dimethoate, and cypermethrin could cause disorder of lipid and amino acid metabolism, induction of oxidative stress, and dysfunction of liver and kidneys, which contributes to the understanding of combined toxic effects of the pesticides revealed by using the metabolomics analysis of the urine and serum profiles.

Prediction of bilateral thyroid carcinoma and lateral cervical lymph node metastasis in PTC patients with suspicious thyroid nodules.

PURPOSE: This study aimed to evaluate the factors associated with bilateral papillary thyroid carcinoma (PTC) and lateral cervical lymph node metastasis (LLNM) in patients with suspicious unilateral PTC. METHODS: This study analyzed patients with suspicious unilateral PTC who were enrolled in a university hospital between 2016 and 2019 in Zhejiang, China. Using logistic regression, the study examined the factors associated with bilateral PTC and LLNM in demographic data, anthropometric measurements, lifestyle factors, medical history, preoperative diagnostic tests, and histopathological factors. RESULTS: A total of 256 patients, with a mean age of 49 years, were enrolled. Bilateral PTC was associated with multifocality (aOR: 5.069, 95% CI: 2.440-10.529, P < 0.001), and contralateral nodule in the upper (aOR: 9.073, 95% CI: 2.111-38.985, P = 0.003) and middle (aOR: 9.926, 95% CI: 2.683-36.717, P < 0.001). LLNM was positively associated with bilateral PTC (aOR, 4.283, 95% CI: 1.378-13.308, p = 0.012), male (aOR, 3.377, 95% CI: 1.205-9.461, P = 0.021), upper location of carcinoma (aOR, 3.311, 95% CI: 1.091-10.053, p = 0.035), and punctate echogenic foci (aOR, 3.309, 95% CI: 1.165-9.394, P = 0.025). Contralateral maximal nodule in the upper (aOR: 0.098, 95% CI: 0.015-0.628, p = 0.014), middle (aOR: 0.114, 95% CI: 0.033-0.522, p < 0.001), and lower (aOR, 0.028, 95% CI: 0.003-0.276, P = 0.002) location were inversely associated with LLNM. CONCLUSION: Upper and middle location of contralateral nodule and tumor multifocality predicted the risk bilateral PTC. Bilateral PTC, male, upper tumor location, punctate echogenic foci and contralateral nodule location in the entire lobes were independent predictors for LLNM.

Hyperbranched polyamidoamine-RGD peptide/si-circICA1 in the treatment of invasive thyroid cancer through targeting of the miR-486-3p/SERPINA1 axis.

Aim: This study aimed to identify molecular markers associated with papillary thyroid cancer (PTC) and investigate the therapeutic potential of targeted nanoscale drugs. Materials & methods: We analyzed the effects of circICA1 and miR-486-3p on B-CPAP cells' proliferation, apoptosis, migration and invasion. The regulation of the miR-486-3p/SERPINA1 axis was explored using quantitative real-time reverse transcription PCR and western blot analyses for metastasis. In vivo, we evaluated the effects of hyperbranched polyamidoamine-RGD peptide/si-circICA1 on PTC growth and metastasis. Results: Enhanced miR-486-3p expression inhibits B-CPAP cells' proliferation and invasion. si-circICA1 delivered via hyperbranched polyamidoamine-RGD peptide nanoparticles shows potential for treating metastasis in PTC. Conclusion: This study identifies key molecular mechanisms underlying PTC invasiveness and suggests a promising therapeutic strategy for PTC using targeted nanoscale drugs.