Predicting cervical lymph node metastasis in OSCC based on computed tomography imaging genomics.

BACKGROUND: To investigate the correlation between computed tomography (CT) radiomic characteristics and key genes for cervical lymph node metastasis (LNM) in oral squamous cell carcinoma (OSCC). METHODS: The region of interest was annotated at the edge of the primary tumor on enhanced CT images from 140 patients with OSCC and obtained radiomic features. Ribonucleic acid (RNA) sequencing was performed on pathological sections from 20 patients. the DESeq software package was used to compare differential gene expression between groups. Weighted gene co-expression network analysis was used to construct co-expressed gene modules, and the KEGG and GO databases were used for pathway enrichment analysis of key gene modules. Finally, Pearson correlation coefficients were calculated between key genes of enriched pathways and radiomic features. RESULTS: Four hundred and eighty radiomic features were extracted from enhanced CT images of 140 patients; seven of these correlated significantly with cervical LNM in OSCC (p < 0.01). A total of 3527 differentially expressed RNAs were screened from RNA sequencing data of 20 cases. original_glrlm_RunVariance showed significant positive correlation with most long noncoding RNAs. CONCLUSIONS: OSCC cervical LNM is related to the salivary hair bump signaling pathway and biological process. Original_glrlm_RunVariance correlated with LNM and most differentially expressed long noncoding RNAs.

Predictive value of systemic inflammatory response-related indices for survival in tongue cancer.

OBJECTIVES: We assessed the potential prognostic significance of the preoperative systemic inflammation index, platelet-to-lymphocyte ratio, and neutrophil-to-lymphocyte ratio in patients who underwent surgical resection. SUBJECTS AND METHODS: This retrospective study included 224 patients with clinicopathologically confirmed squamous carcinoma of the tongue who underwent surgery between August 2009 and December 2017. The optimal cut-off values for the indices were determined by receiver operating characteristic curves. Correlations between the indices and clinicopathological variables were determined by Pearson chi-square or Fisher exact tests. The Kaplan-Meier test was used to compare overall survival between groups (high and low values); the log-rank or Breslow test was used to assess differences in survival. Univariate and multivariate Cox regression models were used to analyze predictive values of the indices as independent indicators of overall survival. Bilateral p values of <0.05 were considered statistically significant. RESULTS: Significant association was found between the indices and sex, tissue grade, tumor location, and lymph nodes metastases (p < 0.05). On Kaplan-Meier analysis, patients with lower values of the indices had longer overall survival (p < 0.05). Univariate and multivariate Cox regression models identified age, lymph node metastases, and neutrophil-to-lymphocyte ratio as independent predictors of overall survival. CONCLUSION: The studied indices have potential prognostic significance in patients with squamous tongue cancer.

Clinical observation of allergic contact stomatitis treated with Kangfuxin solution as adjuvant: case report.

Background: Allergic contact stomatitis (ACS) is common among people with allergic constitution and who have allergy reaction to specific allergen such as drugs, food, and materials because of immune dysfunction. With the development of materials science, the increasing diversity of cosmetics and food additives has gradually raised the incidence rate of ACS. Now systemic and local therapy are adopted in the therapy of ACS. However, the systemic therapy would drop the drugs' concentration after it reaches the treatment area through the layers of human barriers, while the locally-used drugs such as collutory may not be suitable for patients with skin lesion. Kangfuxin contains a variety of biological extracts which is anti-inflammatory and curative and can produce connective tissues whether it's skin or mucous membrane. It can be used not only in non-oral diseases such as gastric ulcer or gynecological diseases, but also in the treatment of recurrent aphthous ulcer and many kinds of stomatitis and has shown good anti-inflammatory and curative effects. This study aimed to explore the effectiveness of Kangfuxin solution as a local-used adjuvant drug to treat ACS. Case Description: We present a 22-year-old male with ACS whose complaint at the first visit was severe pain, accompanied by salivation, tongue enlargement, bleeding, tonsil enlargement, and symptoms of difficulty in eating, fatigue, and dizziness. After the physical and laboratory examination, we found no abnormalities other than a history of eating the kiwi fruit, which is a common allergen. Thus, he was diagnosed as ACS. In this case, we provided a pharmacologic therapeutic intervention of chlorpheniramine (one tablet, three times a day) and Kangfuxin solution (gargle for 15 min, three times a day) with advice that no exposure to the allergen. On the third day, the patient felt no significant relief of symptoms, while one week after the first visit, the symptoms had obviously alleviated and most of the red lip erosion disappeared. The patient recovered completely with no discomfort in ten days after the initial visit. Conclusions: This study investigated the therapeutic effect of Kangfuxin solution combined with chlorpheniramine on ACS.

A deep learning model using convolutional neural networks for caries detection and recognition with endoscopes.

Background: Caries are common, especially in economically undeveloped countries with limited access to medical resources. Sometimes patient cannot even realize that they have oral problems until they feel obvious pain. Deep convolutional neural networks (CNNs) have been widely adopted for medical image analysis and management and have yielded some progress in stomatology while the endoscopes are cheap and easily used in daily life for families or other non-medical situations. Therefore, we created a deep learning model to detect and recognize caries using endoscopic images. Methods: We used 194 images of non-caries and 1,059 images of permanent molar and premolar caries to build a classification and a segmentation model in patients of endoscope images from the Department of Stomatology of People's Liberation Army General Hospital (PLAGH). A classification model combined with an end-to-end semantic segmentation model, DeepLabv3+ was used for segmenting the caries, then we evaluated with a 5-fold cross-validation protocol whereby each fold was used once. Results: In the classification model, the mean area under the curve (AUC) [90% confidence interval (CI)] was 0.9897 (0.9821-0.9956) (P<0.01) In the segmentation model, the mean accuracy was 0.9843 (0.9820-0.9871), the recall was 0.6996 (0.6810-0.7194), the specificity was 0.9943 (0.9937-0.9954), the Dice coefficient was 0.7099 (0.6948-0.7343), and the intersection over union (IoU) was 0.5779 (0.5646-0.6006). Conclusions: We used a deep learning model to monitor caries and encourage their early diagnosis and treatment.

Polyinosine-polycytidylic acid promotes excessive iodine intake induced thyroiditis in non-obese diabetic mice via Toll-like receptor 3 mediated inflammation.

BACKGROUND: Excessive iodine intake and viral infection are recognized as both critical factors associated with autoimmune thyroid diseases. Toll-like receptors (TLRs) have been reported to play an important role in autoimmune and inflammatory disorders. In this study, we aimed to clarify the possible mechanism of TLR3 involved in polyinosine-polycytidylic acid (poly(I:C)) promoting excessive iodine intake induced thyroiditis in non-obese diabetic (NOD) mice. METHODS: Both NOD and BALB/c mice were randomly assigned to four groups: control group (n = 5), high iodine intake (HI) group (n = 7), poly(I:C) group (n = 7) and combination of excessive iodine and poly(I:C) injection (HIP) group (n = 7). After 8 weeks, mice were weighed and blood samples were collected. All the mice were sacrificed before dissection of spleen and thyroid gland. Then, thyroid histology, thyroid secreted hormone, expression of CD3(+) cells and TLR3 as well as inflammatory mRNA level were evaluated. RESULTS: Both NOD and BALB/c mice from HI and HIP group represented goiter and increasing thyroid relative weight. Thyroid histology evidence indicated that only HIP group of NOD mice showed severe thyroiditis with lymphocytes infiltration in majority of thyroid tissue, severe damage of follicles and general fibrosis. Immunofluorescence staining results displayed a large number of CD3(+) cells in HIP NOD mice. Real-time polymerase chain reaction (PCR) results suggested interferon (IFN)-α increased over 30 folds and IFN-γ expression was doubled compared with control group, but interleukin (IL)-4 remained unchanged in HIP group of NOD mice thyroid. Meanwhile, over one third decrease of blood total thyroxine (TT4) and increased thyroid-stimulating hormone (TSH) was observed in HIP group of NOD mice. Only HIP group of NOD mice represented significantly elevation of TLR3 expression. CONCLUSION: Poly(I:C) enhanced excessive dietary iodine induced thyroiditis in NOD mice through increasing TLR3 mediated inflammation.

A newly identified TSHß splice variant is involved in the pathology of Hashimoto's thyroiditis.

Thyrotropin (TSH) is a protein that plays a key role in the control of thyroid function. TSH consists of a common α-subunit and a unique ß-subunit; the latter is responsible for hormone specificity. A novel splice variant of human TSHß was identified in 2009. To date, only the tissue distribution of the human TSHß splice variant mRNA has been studied. Therefore, we aimed to characterize the protein translated from this splice variant. Salting-out, dialysis and concentration of serum proteins were followed by immunoprecipitation to identify the hTSHß splice variant in serum. Stable CHO cell lines expressing the hTSHß splice variant and V5-hTSHα were generated. After co-culture, co-immunoprecipitation was used to determine if the hTSHß splice variant can dimerise with TSHα. We showed for the first time that the hTSHß splice variant exists in human serum and dimerises with TSHα. To explore the relationship between the TSHß splice variant and the pathogenesis of autoimmune thyroiditis, we assessed variations in the mRNA expression of the TSHß splice variant in the peripheral blood leukocytes (PBLs) of Hashimoto's thyroiditis (HT) patients using quantitative RT-PCR. We found that the mRNA expression levels of the TSHß splice variant were higher in the PBLs of HT patients who were not undergoing prednisone therapy (n = 10, P < 0.0001) and in the PBLs of HT patients with a longer duration of illness (>18 months) who were undergoing prednisone therapy (n = 5, P = 0.023) than in those of the control group. This pattern was reversed in the PBLs of HT patients with a shorter duration of illness (<9 months) who were undergoing prednisone therapy (n = 8, P < 0.0001). Dexamethasone inhibition of the TSHß splice variant mRNA expression occurred in a dose- and time-dependent manner. These results demonstrated that the TSHß splice variant may participate in the pathogenesis of HT.

TRAIL and DR5 promote thyroid follicular cell apoptosis in iodine excess-induced experimental autoimmune thyroiditis in NOD mice.

Death receptor-mediated apoptosis has been implicated in target organ destruction in patients with chronic autoimmune thyroiditis. Several apoptosis signaling pathways, such as Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), have been shown to be active in thyroid cells and may be involved in destructive thyroiditis. Thyroid toxicity of iodide excess has been demonstrated in animals fed with an iodide-rich diet, but its pathogenic role remains unclear. The effects of excessive iodine on TRAIL and its death receptor expression in thyroid were investigated. Experimental autoimmune thyroiditis (EAT) was induced by excessive iodine and thyroglobulin (Tg) in non-obese diabetic mice. The expression of TRAIL and its death receptor DR5 was detected by immunofluorescence staining. Following administration of excessive iodine alone, Tg, and excessive iodine combined with Tg, TRAIL-positive cells appear not only in follicular cells but also in lymphocytes infiltrated in the thyroid, whereas DR5-positive cells appear only in follicular cells. Large numbers of CD3-positive cells and a few CD22-positive cells were detected in thyroid. A great amount of follicular cells were labeled specifically by terminal deoxynucleotide transferase-mediated deoxynucleotide triphosphate nick-end labeling assay. Taken together, our results suggest that excessive iodine could induce TRAIL and DR5 abnormal expression in thyroid. TRAIL band with DR5 to promote follicular cells apoptosis thus mediate thyroid destruction in EAT.

[Expression of truncated fragment of human OPG in CHO-DHFR- cells and its bioactivity characterization].

AIM: To obtain high level expression of recombinant human truncated osteoprotegerin (TOPG) with higher bioactivity in CHO-DHFR(-) cells. METHODS: The recombinant vector pcDNA3.1/DHFR-TOPG was constructed and transfected into CHO-DHFR(-) cells by the directions of LipofectAMINE 2000 for stable expression. The stable expression cell strains were screened by selective medium IMDM with 50 mL/L FCS, then serially passed in methotraxate (MTX) for gene amplification. The expression were analyzed by ELISA and RT-PCR. At last, the bioactivity analysis was performed in vitro. RESULTS: The expression level of recombinant truncated human OPG was up to 6 mg/L x 72 h, and it had significant suppression effect on the formation of OLC (P<0.05). CONCLUSION: Recombinant truncated human OPG has high expression and bioactivity. The results make it possible for further studying and clinical implying of OPG.