Objective:To investigate the role and molecular mechanism of sensory neuron-derived exosomes (nExo) in mediating intervertebral disc degeneration (IDD).Methods:A rat IDD model was constructed, with nExo injected into the intervertebral disc. After 4 weeks, the degenerative grades of operated discs were evaluated using histological staining, while the senescent phenotype of nucleus pulposus stem cells (NPSC) in the tissue was evaluated using immunofluorescence staining. For in vitro experiments, 24 hours after the treatment of nExo to NPSC, immunoblotting, flow cytometry, or senescence-associated β-galactosidase staining was applied to evaluate the senescent phenotype of NPSC. Transcriptomics analysis was applied to identify the key molecules that mediate nExo-induced cells senescence. After 4 weeks of injecting nExo and TXN into the rat tail disc degeneration model.Results:nExo increased the degenerative grades of IDD and increased the proportion of TEK +p16 + and TEK +p21 + cells (from 36.32% ±4.04%, 33.69% ±4.56% in IDD group to 56.41% ±5.26%, 50.14% ±8.49% in IDD+nExo group, respectively; t=7.420, P<0.001; t=4.184, P<0.0019, respectively) in the disc tissue. Besides, nExo promoted the expression of p16 and p21 in NPSC and increased the percentage of cells with positive senescence-associated β-galactosidase staining (from 7.32%±1.73% to 58.22%±11.38%, t=7.658, P=0.002), while the percentage of G2/M cells was downregulated (from 18.10%±1.32% to 1.60%±0.67%, t=19.290, P<0.001). Transcriptomic analysis showed that the differential genes of CTRL vs. nExo were closely related to cell senescence, and TXN was screened by intersecting the differential gene set with the cellular senescence gene sets from the published database. Furthermore, we verified that nExo decreased the content of TXN in NPSC, while exogenous TXN downregulated the expression of p16 and p21 in NPSC, reduced the positive cell rate of senescence-associated β-galactosidase staining (from 58.84%±3.99% to 21.68%±8.16%, t=7.048, P=0.021), increased the percentage of G2/M cells (from 1.21%±0.34% to 15.26%±2.60%, t=9.259, P=0.001). TXN significantly reduced the grade of disc tissue degeneration (histological score: 14.33±0.82 in the nExo group; 8.17±1.17 in the nExo+TXN group, t=10.590, P<0.001), significantly increased the content of extracellular matrix (from 10.94±4.35 μg/mg to 50.55±12.16 μg/mg, t=7.512, P<0.001), and reduced the proportion of TEK +p16 + and TEK +p21 + double-positive cells (from 54.92%±4.21% and 60.31%±9.02% to 27.93%±3.26% and 33.75%±8.07%, respectively; t=12.430, P<0.001; t=5.375, P<0.001, respectively). Conclusion:nExo promotes cell senescence and IDD by downregulating TXN in NPSC.

Objectives:To analyze the clinical features and prognosis of patients with medullary thyroid carcinoma combined with papillary thyroid carcinoma (combined carcinoma).Methods:The clinical data of 24 patients admitted to Tianjin Medical University Cancer Hospital from Nov 2012 to Dec 2019 were retrospectively analyzed. The treatment methods, pathological results, and prognosis of all patients were examined.Results:The results showed that combined carcinoma accounted for 10.0% (24/241) of all medullary thyroid carcinoma cases. In the combined cancer group, 45.8% (11/24) patients had lymph node metastasis, and the type of metastasis matched the largest lesion. There were no significant differences in gendex ratio ( χ2=0.164, P>0.05), age at onset ( t=1.381, P>0.05), maximum diameter of lesion ( Z=-1.733, P>0.05), multifocality ( χ2=2.695, P>0.05), and lymph node metastasis in the central ( χ2=1.625, P>0.05) and lateral neck regions ( χ2=1.537, P>0.05) between combined cancer patients and those with MTC alone. The median follow-up time for the 24 patients was 77.6 months. Local recurrence was observed in 2 cases, while no distant metastasis was found. There were no significant differences in disease-free survival, disease-specific survival, and overall survival between combined cancer and pure MTC groups (all P>0.05). Conclusion:The pathological characteristics and prognosis of medullary thyroid carcinoma combined with papillary thyroid carcinoma are similar to those of pure MTC. Therefore, clinical treatment decisions can be similar to pure MTC.

Objective:To analyze the correlations between serum thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) and clinicopathological features in children and adolescents with papillary thyroid carcinoma (PTC).Methods:A retrospective analysis was conduced on the clinicopathological data of children and adolescents (age≤21 years old) with PTC admitted to Tianjin Medical University Cancer Hospital from 2011 to 2019, and then, we used χ 2 test or Fisher′s exact probability test to compare the differences in clinicopathological characteristics between groups with different TgAb and TPOAb status and multivariate logistic regression model analysis to evaluate independent predictors of cervical lymph node metastasis. Results:A total of 304 patients, including 89 males and 215 females, aged 5-21 years (median age 19 years), were enrolled in this study. The comparison between groups with different TgAb and TPOAb status showed that there were significant differences in gender, preoperative thyroglobulin (Tg) level, primary tumor location, number of primary tumors and maximum tumor diameter (all P<0.05), which suggested that TgAb +group ( n=81) and TPOAb +group ( n=84) had relatively better primary tumor characteristics. Patitents with TgAb +and TPOAb +were more common in females and their preoperative Tg level was mostly within the normal range, and there were significant differences in primary tumor location, number of primary tumors and maximum tumor diameter between TgAb +and TgAb -(223 cases) groups (all P<0.05). There was significant difference in the maximum tumor diameter between TPOAb +and TPOAb -(220 cases) groups ( P<0.05). Analysis of risk factors for cervical lymph node metastasis showed that independent risk factors for central lymph node metastasis were maximum tumor diameter>2 cm ( OR=2.84, 95% CI: 1.59-5.07, P<0.001) and extra-thyroid extension ( OR=0.32, 95% CI: 0.17-0.60, P<0.001), and independent risk factors for lateral neck lymph node metastasis included age≤14 years old ( OR=0.34, 95% CI: 0.18-0.67, P=0.002), preoperative Tg +( OR=2.16, 95% CI: 1.10-4.24, P=0.026) and maximum tumor diameter>2 cm ( OR=3.99, 95% CI: 2.33-6.82, P<0.001). Conclusion:It is recommended to test routinely serum TgAb and TPOAb before surgery in children and adolescents with PTC. Preoperative Tg +, age≤14 years, maximum tumor diameter>2 cm, and extra-thyroid extension are risk factors for cervical lymph node metastasis.

Objective:To investigate the BRAF(V600E)gene mutation of pediatric papillary thyroid carcinoma (PTC) and refine their clinicopathological correlates. Methods:Tumor tissue samples of pediatric PTCs (≤18 years old) were collected from tumor tissue bank of Tianjin Medical University Cancer Institute and Hospital from January 2012 to December 2016.The medical records of 22 patients with pediatric PTC were reviewed retrospectively.The frequencies of BRAF(V600E) mutation were evaluated and the correlation between BRAF(V600E) mutation and clinical characteristics were analyzed. Results:BRAF(V600E) mutations were present in 45.5% of cases (10 cases). BRAF(V600E) mutation in pediatric PTC was obviously lower than that in adults PTC(77.7%) ( χ2=11.250, P=0.001). BRAF(V600E) mutation in>12-year-old group (66.7%) was remarkably higher than that in ≤12-year-old group (20.0%) ( P<0.05). BRAF(V600E) mutation in female (69.2%) was greatly higher than that in male (11.1%) ( P<0.05). There was no significant correlation with BRAF(V600E) mutation and multiple tumor, tumor size, highly invasive subtype, extrathyroidal extension, lymph node metastasis and radiological history of infants (all P>0.05). The median follow-up time was 45 months.No patients died and BRAF(V600E) mutation was not associated with the increase of recurrence rate ( P>0.05). Conclusions:BRAF(V600E)gene mutation in pediatric PTC is lower than that in adults. BRAF(V600E) mutation does not portend a more aggressive clinical biological behavior in pediatric PTC.

Objective:To evaluate the role of Tg in diagnosis of lateral cervical lymph node recurrence in papillary thyoid cancer(PTC)after radioactive iodine(RAI) therapy.Methods:From Jan 2012 to Aug 2018, 22 PTC patients who received RAI therapy after operation were reoperated for lateral cervical lymph node recurrence. The clinical data was retrospectively analyzed.Results:The median recurrence time was 30.5 (5-86) months. All 22 patients received RAI therapy after the first operation, and the median dose of RAI was 250mCi(100-700 mCi) and the episode of RAI therapy ranged from 1 to 4. All 22 PTC patients underwent neck reoperation, among which 20 cases were identified to have lymph node metastasis. The median number of lymph nodes dissected was 31 (8-83) and median number of metastatic lymph nodes was 4 (1-19) . The diagnostic accuracy of ultrasonography in detecting lymph node metastasis was 90.9%. Before reoperation, the median Tg was 1.305 (0.10-99.51) μg/L, with the cutoff value of Tg being 0.2 μg/L, and its sensitivity and specificity were 80.0% and 100%, respectively. The median stimulated Tg was 5.89 (0.14-255.80) μg/L in the 10 patients, with the cutoff value of stimulated Tg of 2 μg/L, and its sensitivity and specificity were 88.9% and 100%, respectively.Conclusions:The serum Tg level is helpful for monitoring the recurence of PTC, but recurrence cannot be completely ruled out for those with low Tg.

Objective:To investigate the difference of clinicopathological characteristics between mixed medullary and papillary carcinoma of thyroid and medullary carcinoma coexistent with papillary carcinoma.Method:The clinicopathological data of 3 MMPTC cases and 9 MTC-PTC cases treated at Tianjin Medical University Cancer Institute & Hospital during the past ten years were retrospectively analyzed. The differences in clinical characteristics, pathological characteristics, immunohistochemistry results, treatment and prognosis of the two groups were compared.Results:In the MMPTC group, the median onset-age was 59 years old. 3 patients were all medullary carcinoma colliding with micropapillary carcinoma. The immunohistochemistry results showed that medullary carcinoma and papillary carcinoma showed their distinctive immunohistochemical characteristics. The lymph node metastasis rate was 66.7% (2/3). In MTC-PTC group, the median onset-age was 55; 8 out of 9 patients had an increased preoperative calcitonin level. Medullary carcinoma and papillary carcinoma showed their distinctive immunohistochemical characteristics. Four out of the 9 cases had lymph node metastasis.Conclusion:Compared with MTC-PTC, MMPTC is more common in middle-aged and elder patients, with higher lymph node metastasis rate. The pathogenesis of MTC-PTC is similar to papillary thyroid carcinoma, and the treatment should be individualized. The prognosis of these two groups of patients is fair.

Objective To explore the clinico-pathological characteristics and treatment of thyroid carcinoma in patients under 14 years old.Method The clinical and pathological data of 61 children 14 years old or younger treated for differentiated thyroid carcinoma (DTC) from Jan 2005 to Dec 2014 were retrospectively analyzed.Results There were 26 males and 35 females with the sex ratio of 1 ∶ 1.35.All the 61 patients underwent surgery including lobectomy for ipsilateral foci in 11 cases and total or near total thyroidectomy for bilateral or multi-foci in 50 cases.5 patients had not lymph node metastasis.56 patients had central compartment metastasis and 47 patients had lateral cervical lymph node metastasis.9 patients had distant metastasis and the affected organ was lung.Pathology for all the 61 patients was thyroid papillary carcinoma,35 patients were of highly invasive subtype.The median follow-up time was 3 years and 6 months (30-116 months) with a total survival rate of 100％ while 4 patients suffered from recurrence.Conclusions For below 14 years old DTC patients,the prognosis is better than in adults.The rate of bilateral lesions or multiple foci in ipsilateral lobe and central compartment lymph node or lateral neck lymph node metastasis was higher than in adults.Furthermore,highly invasively pathological subtype is more common in younger patients.

Objective:To determine the clinical features of papillary thyroid microcarcinoma (PTMC) and the risk factors for central compartment lymph node (CCLN) metastasis in PTMC. Methods:Data of 1 401 patients with PTMC who were treated in Tianjin Medi-cal University Cancer Institute and Hospital between January 2014 and December 2014 were retrospectively analyzed. Chi-square test and multivariate Logistic regression analysis were used to study the risk factors. Results:With regard to clinicopathological features, the sex ratio is 1:3.4 in patients with PTMC. CCLN metastasis affected 427 (30.5%) of the total 1 401 patients. Age (χ2=14.587, P<0.01), sex (χ2=21.636, P<0.01), tumor multifocality (χ2=35.505, P<0.01), tumor size (χ2=58.868, P<0.01), tumor site (χ2=8.385, P<0.05), and extracapsular/extraglandular invasions (χ2=26.481, P<0.01) were significantly correlated with CCLN metastasis. For patients with a soli-tary primary tumor, tumor location in the lower third of the thyroid lobe was associated with a higher risk of CCLN metastasis (48.1%). The male gender, age<45 years, tumor size>6 mm, extracapsular spread, and tumor bilaterality were independently correlated with CCLN metastasis. Conclusion:A prophylactic neck dissection of the central compartment must be considered particularly in male PT-MC patients with age<45 years, tumor size>6 mm, extracapsular spread, and tumor bilaterality.

Objective To analyze the clinical and pathological features of follicular variant of papillary thyroid carcinoma (FVPTC).Methods Clinical data of 131 FVPTC patients diagnosed and treated between January 2006 and June 2012 were retrospectively analyzed.Results Of the 131 FVPTC patients,the median age at diagnosis was 45 years and 74.0％ patients were female.Pathologically 29％ (38 patients) of the FVPTC patients were encapsulated,and 71％ (93 patients) were nonencapsulated.Compared with classical papillary thyroid carcinoma (CPTC),FVPTC patients were more likely to have lower ultrasound diagnostic accuracy rate,frozen section accuracy rate,tumor muhicentricity,tumor bilaterality,lymph node metastasis,lateral lymph node metastasis rate,N staging,TNM stage,ATA risk and higher M staging and concomitant chronic thyroiditis rate (all P ＜ 0.05).Moreover,there were significant differences between nonencapsulated and encapsulated follicular variant of papillary thyroid carcinoma in tumor size,TSH level,ultrasound diagnostic accuracy rate,extrathyroid invasion,T staging,lymph node metastasis,N staging,TNM staging,ATA risk and recurrence rate (all P ＜ 0.05).Conclusions Compared with CPTC,FVPTC have different clinical and biological features.It's necessary for different management strategies for different FVPTC patients.

ObjectiveTo investigate the clinical biocharacteristics,treatment,prognosis and the factors that influence prognosis of anaplastic thyroid carcinoma(ATC). MethodsThe clinical data of 108 ATC patients treated at our institution from January 1981 to April 2009 and follow-up results were retrospectively reviewed.ResultsThe median survival time of 108 patients was 6 months.The overall 1-year,2-year,5-year survival rate was 40.3％,30.9％ and 21.9％ respectively.Univariate analysis showed the factors influencing the prognosis of ATC patients were tumor size, distant metastases, stage,leukocytosis, radiotherapy, localresection, postoperativeradiotherapyandmultimodalitytherapy.Multivariate analysis indicated that tumor size,stage,leukocytosis and radiotherapy were independently associated with the prognosis.ConclusionsAnaplastic thyroid carcinoma is rare but highly aggressive malignancy with poor prognosis. ATC patients should receive multimodality therapy,especially local resection and postoperative radiotherapy.Even inoperable patients could benefit from radiotherapy.