ACTA ENDOCRINOLOGICA (BUC)

Objective. This research aim was to evaluates the role of the pre-ablation neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) as predictors of distant metastases in patients with differentiated thyroid cancer (DTC). Methods. A retrospective analysis was given to 140 patients with DTC who received 131I remnant ablation after surgery. The patients were divided into two groups based on the existence of distant metastasis. Results. The two groups showed no significant difference in age, gender, WBCs, neutrophils, monocytes, eosinophils, basophils and whether the tumor was multifocal. In the univariate analysis, significant differences were found in tumor size (p=0.021), lymphocyte (p=0.012), NLR (p=0.027), and LMR (p=0.007). According to the ROC curves, NLR had an AUC of 0.612 ± 0.097 with a cut-off value of 1.845, sensitivity of 60.0%, and specificity of 66.2% (p=0.027). LMR had an AUC of 0.638 ± 0.095 with a cutoff value of 4.630, sensitivity of 84.6%, and specificity of 35.4% (p=0.007). In the multivariate analysis, larger tumor size (OR=5.246, 95% CI 1.269-10.907, p=0.009) and higher NLR (OR=2.087, 95% CI 0.977-4.459, p=0.034) were statistically significant for distant metastases. Conclusion. This research reveals that pre-ablation NLR and tumor size are significantly statistically correlated with distant metastases in patients with DTC.

Background. The high recurrence rate and low survival rate of ovarian cancer (OC) patients are closely related to an anoxic environment. We aim to study the mechanism of long non-coding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP) on hypoxia ovarian cancer cells (OCC) and its mechanism was investigated. Methods. Knockdown and overexpression of HOTTIP in human OCC (SKOV-3, OVCAR3) were performed. The expression levels of HOTTIP and HIF- 1α were monitored by qRT-PCR and WB. Transwell was conducted to validate the cell migration and invasion. ELISA was performed to calculate VEGF concentration in cells. Cell viability was monitored by CCK-8. Cell apoptosis and cycle were tested by flow cytometry. RNA pull-down was used to analyze the interaction between HIF-1α and HOTTIP. Results. HOTTIP was highly expressed in OCC. After HOTTIP knockdown, HIF-1α expression and VEGF concentration in OCC were decreased. Cell migration, invasion, and cell viability were decreased. Cell apoptosis rate and G0/G1 phase cells were increased. RNA pull-down indicated a direct interaction between HIF-1α and HOTTIP. Conclusions. HOTTIP formed a positive feedback loop with HIF-1α to promote the development and metastasis of hypoxia ovarian cancer. This study provided theoretical support for the development of new OC treatment strategies.

Objective. To investigate the effect of puerarin (Pue) on the proliferation and differentiation of osteoblasts and the expression of type I collagen(Coll I) mRNA in a high-glucose (HG) environment, and to provide evidence for the clinical treatment of diabetic osteoporosis(DOP). Subjects and Methods. The proliferation of osteoblasts from three groups – the control group, the HS group, and the HG+Pue (10-8-10-6 M) group – was cultivated for 72 h and evaluated using the methyl thiazolyltetrazolium (MTT) assay. Results. The MTT values and the ALP activities in all experimental groups were significantly lower than those in the control group, and the MTT values and the ALP activities in the HG+Pue group were significantly higher than those in the HS group. Coll I mRNA expression in all experimental groups was significantly lower than that in the control group, while that in the HG+Pue group was significantly higher than that in the HG group. Conclusions. The proliferation and differentiation of osteoblasts and the expression of Coll I mRNA were inhibited by high glucose, but Pue can increase the proliferation and differentiation as well as the expression of Coll I mRNA in the osteoblasts, indicating that Pue could be therapeutically beneficial against DOP.

Context. Peripheral nerve lesions are a major complication of diabetes mellitus, the main clinical manifestations of which are numbness and pain involving the limbs. Objective. To determine the correlation between pregabalin treatment and diabetic peripheral neuropathic pain. Design. An experimental animal study in BALB/c mice. Subjects and Methods. Diabetes models are established by injecting streptozotocin (STZ) into the abdominal cavities of mice. The correlation between the treatment effect, time, and dosage of pregabalin was determined. The effect of a type 1 organic cation transporter (Octn1) in the absorption of pregabalin was evaluated. Results. Pregabalin reduced tactile allodynia in diabetic mice. The best analgesic effect occurred when intestinal absorption was increased. Octn1 mediated pregabalin entry into intestinal epithelial cells, which influenced the absorption of pregabalin with a timedependent fluctuation in the small intestine. Peripheral nerve damage caused by diabetes was dependent on time and dose of pregabalin, which was related to the regular expression of Octn1 in small intestinal epithelium. Conclusions. Peripheral nerve damage caused by diabetes was dependent on time and dosage of pregabalin, which was related to the regular expression of Octn1 in small intestinal epithelium.

Objectives. This work aimed to study the influences of carbonated beverages (CBs) on the testis growth and the expression levels of androgen receptor (AR) of mice. Methods. Two experimental groups of 30 mice each PEP-1 and PEP-2 drank 50% and 100% Pepsi-Cola, respectively for 15 days. Other 2 experimental groups of 30 mice each COC-1 and COC-2 drank 50% and 100% Coca- Cola, respectively for 15 days. The control group (CG) of 30 mice drank water. Bilateral testes were harvested aseptically on days 0, 5, 7, 10, 13 and 15. Real-time PCR and Western blot were implemented to detect levels of androgen receptor (AR) mRNA and protein in testis tissues. Results. Testes masses of PEP-2, COC-1 and COC-2 were greater than those of PEP-1 and CG (P < 0.05). On day 15, testis longitudinal diameter (TLD) of CBs-treated mice was increased as compared to CG. TLD, testes transverse diameters (TTD) and AR proteins levels of PEP-2 and COC-2 were increased in comparison with CG (P<0.05). Serum testosterone concentrations of PEP-2 were higher than that of COC-1 and CG (P < 0.05). Levels of AR mRNAs of four CBs-treated mice were increased by 60.18%, 67.26%, 65.93% and 78.76%. Conclusions. A high concentration of Coca-Cola and Pepsi-Cola could raise TLD and TDD, enhance testosterone secretion, and increase serum EGF concentrations.

Background. Blood glucose levels in the human body continuously fluctuate within a certain range. Intermittent hyperglycemia has adverse effects on vascular endothelial\r\ncells and pancreatic beta cells. A few studies have found that blood glucose fluctuation induced apoptosis of both endothelial cells and pancreatic beta cells, possibly due to oxidative stress. This study aimed to determine the\r\neffects of blood glucose fluctuation on hepatocytes in vivo.\r\nMaterials and Methods. To induce intermittent hyperglycemia, rats were intermittently treated with 50% glucose\r\ninjection to fluctuate blood glucose between 5.5 mmol/L and 20.0 mmol/L. The rats with intermittent hyperglycemia were treated with either low dose (0.35 mg/kg?min) or high dose\r\n(0.70 mg/kg?min) N-acetylcysteine (NAC). The rats infused with saline were used as control. Apoptosis was assessed by TUNEL assay. Malondialdehyde (MDA) and superoxide dismutase (SOD) in the liver, as well as plasma ALT, AST, TBIL, and IBIL, were examined using colorimetric kits.\r\nResults. Liver function was lower in the rats with intermittent hyperglycemia than in control rats. Hepatocytes exposed to blood glucose fluctuation were more likely\r\nto undergo apoptosis compared to control group (0.07?0.016 vs. 0.015?0.009, P<0.01). The expression of Caspase-3 and\r\ncleaved Caspase-3 was significantly higher in the IHG group than in the SAL group (0.111?0.015 vs. 0.07?0.011; 0.064?0.012 vs. 0.004?0.001, P<0.05).The expression of\r\nBax and the ratio of Bax to Bcl-2 were significantly higher in the IHG group than in the SAL group (0.20?0.05 vs. 0.10?0.02; 0.55?0.20 vs. 0.20?0.05, both P<0.01). When treated with NAC, the liver function of rats with intermittent hyperglycemia improved remarkably, and hepatocyte apoptosis decreased.\r\nConclusion. Blood glucose fluctuation appears to be detrimental to liver function, but this effect can be ameliorated by NAC.

Aim. To establish a nomogram combining preoperative ultrasonic and clinical features for predicting lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN) metastasis in papillary thyroid carcinoma (PTC) patients. Methods. Preoperative ultrasonic and clinical variables of patients with PTC from 2014 to 2021 were retrospectively analyzed. The risk factors associated with LN-prRLN metastasis were identified and validated through a developed nomogram model based on univariate and multivariate logistic regression analysis. Results. A total of 615 patients (690 lesions) were enrolled for the training dataset and 207 patients (226 lesions) for the validation dataset with 54 (6.57%) patients developing LN-prRLN metastasis. Multivariate logistic regression analysis demonstrated that the preoperative ultrasound measurement of larger tumors (≥20 mm), higher TI-RADS category (category 5), and higher thyroglobulin level (9.86 ng/mL) in patients with PTC were predictive factors for LN-prRLN metastasis. The nomogram model was established and verified yielding a relatively good predictive performance in the training and validation dataset (AUC: 0.868 vs. 0.851). Conclusions. The nomogram combining preoperative ultrasonography with clinical features in this study is highly predictive of LN-prRLN metastasis in patients with PTC, which may provide more personalized recommendations for clinicians in preoperative decisionmaking for complete dissection of LN-prRLN.

Background. To evaluate iodine status and the prevalence of thyroid disorders in different populations of Zhoushan Island, China.\r\nMethods. A total of 3284 inhabitants of Zhoushan Island were surveyed, including 1389 urban residents, 737 salt workers, 502 peasants, 362 fishermen, and 294 monks from Mount Putuo. All subjects, except for salt workers, consumed iodized salt. A thyroid ultrasound was performed and serum levels of\r\nthyroid hormones and thyroid peroxidase antibody were measured.\r\nResults. The median urinary iodine concentration was significantly higher in subjects who consumed iodized salt than in those who consumed non-iodized salt. No significant differences were noted in the prevalence of thyroid ultrasound abnormalities and functional thyroid disorders between subjects who consumed non-iodized and iodized salt except between salt workers and monks from Mount Putuo. The prevalence of thyroid ultrasound abnormalities differed\r\nsignificantly between males and females and was positively correlated with advanced age (r=0.212, P<0.001).\r\nConclusions. Iodine intake is considered adequate, more than adequate, or excessive amongst the study populations. The\r\nprevalence of both thyroid ultrasound abnormalities and functional thyroid disorders is extremely high in Zhoushan Island. Advanced age and female gender are significant predictors of thyroid ultrasound abnormalities.

Objective. To investigate the correlation between serum levels of 25-hydroxy vitamin D [25(OH)D] and the visceral fat area of patients with type 2 diabetes mellitus (T2DM) in the context of different bone mass. Materials and Methods. A total of 180 patients with T2DM were randomly selected for bone mineral density (BMD) examination. According to the results, they were divided into three groups: T2DM normal bone group (group A); T2DM bone mass reduction group (group B); T2DM osteoporosis group (group C). Result. Serum 25(OH)D levels in NC group, A group, B group and C group decreased in turn, and Visceral fat area (VFA) in group B and group C were significantly higher than those in group A and NC [(29.41±4.87) vs. (22.76±4.23) vs. (17.78±3.61) vs. (9.70±3.01), P<0.05], [(117.76±38.79), (125.08±37.90) vs. (89.79±26.51), (97.53±28.61), P<0.05]. Pearson correlation analysis showed that L1-L4 lumbar vertebrae bone density was positively correlated with 25(OH)D and VFA; left femoral neck bone density was positively correlated with 25(OH)D, and negatively correlated with VFA. Conclusion. Serum 25(OH)D and VFA may be associated with the development of T2DM combined with OP.

No inheritance of early-onset female-related type 2 diabetes was reported within Chinese families. In this study, we aim to describe the inheritance pattern of type 2 diabetes in a 3-generation family and identify the gene responsible for type 2 diabetes. Genome-wide multipoint parametric linkage analysis revealed a maximum multipoint logarithm of odds (lod) score of 2.1 for a locus being associated with type 2 diabetes in this family on chromosome 20p11.2-12 between 23.5~30.8cM. Type 2 diabetes may be transmitted as an autosomal dominant trait with a high female-related penetrance in this family. Here we describe the first genetic locus for type 2 diabetes at chromosome 20p11.2-12. This region contains 8 known or predicted genes (PLCB1, PLCB4, LAMP5, PAK7, ANKEF1, SNAP25, SLX4IP, and JAG1). Gene SNAP25 which linked to energy or glucose homeostasis associated phenotypes may play a role in the development of type 2 diabetes in this family.