[Correlation between BRAFV600E mutation and aggressive biological behavior of papillary thyroid carcinoma].

The current study analyzed the mutation rate of BRAFV600E in papillary thyroid carcinoma patients and the correlation between BRAFV600E mutation and aggressive biological behavior of papillary thyroid carcinoma. A total of 160 patients with papillary thyroid carcinoma who underwent surgical treatment in the Affiliated Cancer Hospital of Zhengzhou University from October 2020 to November 2021 were retrospectively included. All patients underwent BRAFV600E gene detection. There were 37 males and 123 females, with a mean age of (46.5±11.1) years. The mutation rate of BRAFV600E was 86.3% (138/160). There was no significant correlation between the mutation of BRAFV600E and aggressive factors such as age (P=0.917), single focal/multifocal tumor (P=0.673), tumor size (P=0.360), tumor invasion (P=0.150) and regional lymph node metastasis (P=0.406). Therefore, for papillary thyroid cancer, mutations in a single gene like BRAFV600E fail to determine more active diagnosis and treatment.

[Preliminary study on the expression of MIF in HCC tissues and its relationship with ERK1/2 signaling pathway].

Objective: To investigate the expression of Macrophage migration-inhibitory factors (MIF) in hepatocellular carcinoma (HCC) tissues and its interaction with ERK1/2 signaling pathway, so as to establish a theoretical basis for further studying the molecular mechanism of MIF promoting HCC. Methods: From February 2020 to August 2021, 52 cases of hepatocellular carcinoma (HCC) tissues based on hepatitis B cirrhosis (HBV-LC) and 52 cases of adjacent tissues in Tianjin Medical University Cancer Hospital and 940th Hospital of Joint Logistic Support Force of PLA were collected as the experimental group, including 39 males and 13 females, aged 35-65 years. And 20 cases of normal liver tissue were selected as the control group. Immunohistochemistry was used to detect the expression of MIF, ERK1/2 and p-ERK1/2 proteins in liver tissues of the two groups, and in situ hybridization was used to detect the expression of ERK1/2 nucleic acid in liver tissues of the two groups.HepG2 HCC cells and L-02 normal hepatocytes were co-cultured with different concentrations of rMIF, the expression and phosphorylation levels of ERK1/2 and JNK1 proteins in the two kinds of liver cells were detected by Western-blot, and the expression levels of ERK1/2 nucleic acids in the two kinds of liver cells were detected by RT-PCR. One-way ANOVA was used for measurement data and χ2 test was used for counting data. Results: The expressions of MIF, ERK1/2, p-ERK1/2 and ERK1/2 mRNA were significantly increased in HCC and para-cancer tissues (the expression of MIF in HCC group was 78.8%, and that in adjacent group was 75.0%; ERK1/2 80.8% in HCC group and ERK1/2 71.8% in paracancerous group. The expression of p-ERK1/2 75.0 % in HCC group and 46.2% in paracancerous group were respectively detected. ERK1/2 mRNA was expressed in HCC group 76.9%, ERK1/2 mRNA expression in paracancerous group 78.8%), and the differences were statistically significant compared with normal liver tissues (P<0.05), but there was no significant difference between HCC and para-cancer tissues (P>0.05). The expressions of ERK1/2, p-ERK1/2 and ERK1/2 mRNA in HepG2 HCC cells were significantly increased with the increase of rMIF concentration, and the increase was most obvious when rMIF concentration was 200 ng/ml, and the difference was statistically significant compared with L-02 normal hepatocytes (P<0.05). Conclusion: MIF, ERK1/2 and p-ERK1/2 are highly expressed in HCC tissues and HepG2 HCC cells, suggesting that MIF promotes the occurrence and development of hepatocellular carcinoma through ERK1/2 signaling pathway.

[Association of extranodal extension and lymph node ratio with radioactive iodine-refractory papillary thyroid cancer].

Objective: To investigate the related factors of radioiodine-refractory thyroid cancer (RAIR-DTC) and the increase of cumulative iodine treatment dose. Methods: The data of patients with papillary thyroid cancer who underwent surgery and iodine treatment for the first time in the Affiliated Cancer Hospital of Zhengzhou University from January 2015 to December 2017 were retrospectively analyzed. The related factors of RAIR-DTC and the increase of cumulative iodine treatment dose were explored. Results: A total of 650 patients were enrolled, including 217 males (33.4%) and 433 females (66.6%), aged 45 (34, 53) years. There were 123 patients (18.9%) over 55 years old, 171 patients (26.3%) with extranodal extension and 18 patients (2.8%) with distant metastasis. The median lymph node ratio was 0.22 (0.11, 0.33). Twenty patients (3.1%) had an accumulated iodine treatment dose>400 mCi and 19 patients (2.9%) had RAIR-DTC. Multivariate logistic regression analysis showed that extranodal extension (OR=19.833, 95%CI: 6.057-73.325, P<0.001) was related factors for the increase of cumulative iodine treatment dose. Age>55 years old (OR=3.322, 95%CI: 1.136-9.466, P=0.024), distant metastasis (OR=10.059, 95%CI: 2.508-38.888, P<0.001), extranodal extension (OR=5.278, 95%CI: 1.707-19.813, P=0.006) and lymph node ratio (OR=34.724, 95%CI: 2.749-384.575, P=0.004) were related factors for RAIR-DTC. Conclusions: Extranodal extension and lymph node ratio are related factors for RAIR-DTC. In clinical practice, more attention should be paid to the influence of different lymph node metastasis characteristics on the occurrence of RAIR-DTC and the cumulative therapeutic dose of iodine.

Study of pharyngeal airway morphology with CBCT: Benefits of four premolar extraction orthodontic treatments.

Background and Aim: Four premolars extractions are routine procedures for correction of malocclusion, but will inevitably lead to a reduction of tongue space, whether this will weaken the pharyngeal airway remains a controversy. Patients and Methods: Cone-beam computed tomography (CBCT) radiographs of 80 patients who completed four premolar extraction orthodontic treatments were collected and divided into three anteroposterior skeletal groups according to the ANB (angle subspinale to nasion to supramentale) value. Linear, angular, cross-sectional area, and volumetric dimensions of the pharyngeal airway were measured using Dolphin Imaging 11.9 software. One-way analysis of variance and Pearson's correlation coefficient test were performed to assess the intergroup comparisons. Treatment changes were evaluated with two-sample t-tests. Results: In intergroup comparisons, vertical linear and cross-sectional area differences were identified in S-Go/N-Me, VD1, VD1/N-Me, VD2/N-Me, AA, OAA and OMINI (p<0.05), while other measurements showed no significant differences. Angle2, the tilting degree of the pharyngeal airway, showed a positive correlation with ANB (p<0.05). As for the treatment changes, a significant increase was found in the pharyngeal airway in the Class I group (OUA p<0.05, VD1 p<0.001, VD2 p<0.05) and Class II group (VD1 p<0.001. VD2, p<0.05), and inversely, a significant decrease was found in the pharyngeal airway in the Class III group (OAA p<0.05, OMINI p<0.05, OUA p<0.05). No volumetric difference was identified. Interestingly, regarding the preoperative pharyngeal airway size, values trended to the mean value significantly. Conclusion: Four premolar extraction orthodontic treatments did not affect the pharyngeal airway volume except for the vertical liner and cross-sectional area dimensions. The trend of the gold standard suggested a positive influence of four premolar extraction orthodontic treatments.

[Thoughts on enacting and carrying out for reoperative procedures in thyroid surgery].

In recent years, with the improvement of the incidence of thyroid tumors and the extensive development of thyroid surgery in primary hospitals, the proportion of thyroid cancer patients requiring reoperation has continued to increase. In spite of different reasons of reoperation, the risk of serious complications will increase after reoperation compared with first operation. Undoubtedly, the doctors will have to face new challenges to make more appropriate surgery program. Before reoperation, both the operation benefits and the corresponding risks should be considered comprehensively. As far as possible, the individual treatment should be recommended on the basis of standardized treatment, and it will be better to strike a balance between radical surgery and function protection. Consequently, low-grade doctors should be cautious to perform these reoperations.

DNA barcoding and phylogenetic relationships of Ardeidae (Aves: Ciconiiformes).

The avian family Ardeidae comprises long-legged freshwater and coastal birds. There has been considerable disagreement concerning the intrafamilial relationships of Ardeidae. Mitochondrial cytochrome c oxidase subunit I (COI) was used as a marker for the identification and phylogenetic analysis of avian species. In the present study, we analyzed the COI barcodes of 32 species from 17 genera belonging to the family Ardeidae. Each bird species possessed a barcode distinct from that of other bird species except for Egretta thula and E. garzetta, which shared one barcoding sequence. Kimura two-parameter distances were calculated between barcodes. The average genetic distance between species was 34-fold higher than the average genetic distance within species. Neighbor-joining and maximum likelihood methods were used to construct phylogenetic trees. Most species could be discriminated by their distinct clades in the phylogenetic tree. Both methods of phylogenetic reconstruction suggested that Zebrilus, Tigrisoma, and Cochlearius were an offshoot of the primitive herons. COI gene analysis suggested that the other herons could be divided into two clades: Botaurinae and Ardeinae. Our results support the Great Egret and Intermediate Egret being in separate genera, Casmerodius and Mesophoyx, respectively.

[The role of combined BRAFV600E gene detection in the diagnosis of thyroid nodule determined as Bethesda â ¢ by fine-needle aspiration].

Objective: To analyze the malignant probability of thyroid nodules with the diagnosis of atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) determined by fine-needle aspiration (FNA) and to explore the value of the combined application of BRAFV600E gene detection for the diagnosis of benign and malignant thyroid nodules. Methods: A total of 114 patients including 20 males and 94 females, aged 16-76 years old with thyroid nodules underwent FNA examination and surgical treatment in the Affiliated Cancer Hospital of Zhengzhou University from October 2018 to November 2019 were retrospectively analyzed. Postoperative histopathological results were used as the gold standard for the diagnosis of malignant thyroid nodules. The malignant rate of thyroid nodules with the diagnosis of AUS/FLUS was evaluated. Differential diagnostic efficacy of preoperative FNA combined with BRAFV600E gene detection for papillary thyroid carcinoma (PTC) was analyzed by McNemer test and diagnostic test evaluation method. Results: The mutation rate of BRAFV600E gene was 84.76% (89/105) in PTC. PTC accounted for 57.14% (12/21) of the patients with the diagnoses of AUS/FLUS determined by FNA. The specificity, sensitivity, positive predictive value and negative predictive value of BRAFV600E mutation examination for the diagnosis of malignant thyroid nodules determined preoperatively as AUS/FLUS were 9/9, 5/12, 5/5 and 9/16, respectively. BRAFV600E mutation examination could improve the detection rate of PTC in patients with AUS/FLUS (OR=0.438, 95%CI=0.251-0.763, P=0.016). Conclusion: FNA combined with BRAFV600E mutation examination can significantly improve the detection rate of malignant thyroid nodules diagnosed preoperatively as AUS/FLUS.

HMG-CoA reductase inhibitors induce apoptosis of lymphoma cells by promoting ROS generation and regulating Akt, Erk and p38 signals via suppression of mevalonate pathway.

Statins, the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are widely used cholesterol-lowering drugs. Convincing evidence indicates that statins stimulate apoptotic cell death in several types of proliferating tumor cells in a cholesterol-lowering-independent manner. The objective here was to elucidate the molecular mechanism by which statins induce lymphoma cells death. Statins (atorvastatin, fluvastatin and simvastatin) treatment enhanced the DNA fragmentation and the activation of proapoptotic members such as caspase-3, PARP and Bax, but suppressed the activation of anti-apoptotic molecule Bcl-2 in lymphoma cells including A20 and EL4 cells, which was accompanied by inhibition of cell survival. Both increase in levels of reactive oxygen species (ROS) and activation of p38 MAPK and decrease in mitochondrial membrane potential and activation of Akt and Erk pathways were observed in statin-treated lymphoma cells. Statin-induced cytotoxic effects, DNA fragmentation and changes of activation of caspase-3, Akt, Erk and p38 were blocked by antioxidant (N-acetylcysteine) and metabolic products of the HMG-CoA reductase reaction, such as mevalonate, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). These results suggests that HMG-CoA reductase inhibitors induce lymphoma cells apoptosis by increasing intracellular ROS generation and p38 activation and suppressing activation of Akt and Erk pathways, through inhibition of metabolic products of the HMG-CoA reductase reaction including mevalonate, FPP and GGPP.