Objective To investigate T cell subtypes and their functions in liver immune microenvironments among patients with alveolar echinococcosis (AE) using single-cell RNA sequencing (scRNA-seq). Methods Four AE patients that were admitted to Qinghai Provincial People’s Hospital in 2023 for hepatic surgery for the first time were enrolled, and liver specimens were sampled 1 cm (peri-lesion, PL group) and > 5 cm from AE lesions (distal lesion, DL group) among each patient. Finally, a total of eight liver specimens were sampled from four AE patients for scRNA-seq analysis. Genome and transcriptome data of liver specimens were processed using the software Cell Ranger and R package. Differentially expressed genes (DEGs) and their biological functions were analyzed using gene ontology (GO) enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis, and the primary intercellular communication patterns and interaction mechanisms were identified among T cell subtypes in liver specimens using the CellChat package. In addition, the developmental stages of T cells were subjected to trajectory analysis with the monocle package to investigate the expression of genes associated with cell growth and tumor transformation, and to predict the developmental trajectories of T cells. Results All four AE patients were female, with a mean age of (25.00 ± 9.06) years, and there were three cases from Jiuzhi County, Golog Tibetan Autonomous Prefecture and one case from Chengduo County, Yushu Tibetan Autonomous Prefecture, Qinghai Province. The viability of single-cell samples from eight liver specimens was 90.41% to 96.33%, and a total of 81 763 cells were analyzed, with 19 cell types annotated. Of these cell types, 13 were immune cells (87.60%), and T cells (33.13%), neutrophils (15.40%), and natural killer cells (11.92%) were the three most common cell types. Re-clustering of 27 752 T cells and proliferative T cells identified 10 distinct T cell subtypes, with CD8⁺ cytotoxic T cells (23.43%), CD8⁺ naive T cells (12.80%), and CD4⁺ effector memory T cells (17.73%) as dominant cell types. The proportions of T helper 2 (Th2) cells (5.19% vs. 3.63%; χ² = 38.35, P < 0.01) and CD4⁺ effector memory T cells (21.59% vs. 13.67%; χ² = 244.70, P < 0.01) were significantly higher in liver specimens in the PL group than in the DL group, and the proportion of CD4⁺ helper T cells was significantly lower in the PL group than in the DL group (7.50% vs. 14.75%; χ² = 330.52, P < 0.01). KEGG pathway analysis revealed that Th2 cells were significantly enriched in cell apoptosis and multiple cancer-associated pathways, and CD4⁺ effector memory T cells were significantly enriched in the regulation of cytokines and chronic inflammation, while CD4⁺ helper T cells were significantly enriched in immune responses regulation. Trajectory analysis of T cells showed that CD4⁺ helper T cells were at an earlier developmental stage relative to Th2 cells and CD4⁺ effector memory T cells, and the expression of inhibitor of DNA binding 3 (ID3), thioredoxin interacting protein (TXNIP), Bcl2-associated athanogene 3 (BAG3) and heat shock protein family B (small) member 1 (HSPB1) genes appeared a tendency towards a decline over time. Conclusions CD4⁺ effector memory T cells and CD8⁺ cytotoxic T cells are primary interacting cells in the liver specimens of AE patients. Reduced expression of Th2 cells and CD4⁺ helper T cells contributes to an inhibitory immune microenvironment, which promotes immune evasion by Echinococcus multilocularis, and Th2 cells are significantly enriched in multiple cancer-associated pathways, which may be linked to the invasive growth of E. multilocularis.

Pediatric and adolescent thyroid cancer is a rare malignant tumor with etiology,clinical-pathological features,and prognosis dif-fering from adult thyroid cancer,exhibiting an increasing incidence over the years.Compared to adults,children and adolescents are more sensitive to radiation,making it a definite risk factor for the development of thyroid cancer in this population.Radiation primarily originates from nuclear accidents and medical exposure.This review comprehensively explores the molecular changes induced by radiation leading to thyroid cancer in children and adolescents,aiming to raise awareness of the hazards posed by radiation to the thyroid health of this specific age group.The in-depth analysis provided in this medical review serves as a valuable reference for gaining insights into the disease mechan-ism and guiding future research endeavors.

As the most common endocrine malignant tumor,the incidence rate of thyroid cancer is increasing year by year.However,the vast majority of subtypes have a good prognosis after traditional surgery,TSH suppression therapy and 131I treatment.With the progressive development of modern medicine,for a few thyroid cancers with poor effects of traditional treatment,molecular diagnosis and targeted therapy have further enriched the therapeutic means of thyroid cancer,in which BRAF mutation is widely present in thyroid cancer,but it often shows primary resistance or poor response to 131I therapy.The factors leading to primary or secondary resistance to targeted drugs with BRAF mutation may include genomic instability,expansion of resistant clones,occurrence of intrinsic mutations,or novel genetic and epigenetic alterations.In this article,we will review the research progress in targeted therapy resistance in BRAF-mutant thyroid cancer.

Objectives:To explore the clinicopathological characteristics and prognostic risk factors in differentiated thyroid cancer (DTC) patients with lung metastasis.Methods:Patients of differentiated thyroid cancer with lung metastasis in Tianjin Medical University Cancer Institute & Hospital were enrolled from Jan 1, 2010 to Dec 31, 2016. The clinicopathological characteristics and risk factors affecting the prognosis were analyzed retrospectively.Results:A total of 65 DTC patients with lung metastasis were collected in this study, including 56 patients with papillary thyroid carcinoma and 9 patients with follicular thyroid carcinoma; 23 patients died and 42 patients survived. Median follow-up time was 99.4 months. There were 18 males, 47 females. Age 14-73 years, median age 51.0 years. High incidence of DTC lung metastasis was 50-59 years for males and 40-49 years for females. Based on AJCC 8th edition TNM staging, there were 37 patients in stage Ⅱ (age <55 years) and 28 patients in stage Ⅳb (age ≥55 years). The number of 131Ⅰ treatments performed ranged from 1 to 13 times, with a mean of 3.9 times. Firty-five patients were with lung metastasis alone, and 10 patients with lung metastasis and distant metastasis in other organs. Eleven patients suffered from hypoparathyroidism after 131Ⅰ treatment. COX multifactorial regression analysis found that age was independent risk factor affecting prognosis, multiple organs distant metastasis and pathologic subtype were relative risk factors affecting prognosis. There was no correlation between gender, number of 131Ⅰ treatments and poor prognosis. Conclusions:DTC has a high survival even with the occurrence of lung metastasis, but the prognosis is poor when combined with multi-organ metastasis. Age and multiple organ distant metastatic are independent risk factors affecting prognosis.

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 evaluate postoperative calcitonin level as a prognostic marker in long-term follow-up of medullary thyroid carcinoma(MTC).Methods:Clinical data of 146 MTC cases treated at Tianjin Medical University Cancer Institute and Hospital from Jan 2011 to Dec 2019 were reviewed retrospectively. The relationship between postoperative calcitonin and disease-free survival was analyzed. According to the level of calcitonin six months after operation, patients were divided into normal level group and elevated group.Results:The median tumor size in those 146 cases was (1.78±1.22)cm, and 81 cases had lymph node metastasis. After 6 months of follow-up, 89 cases had normal calcitonin, with median tumor size of (1.63±1.20)cm, and 35 cases had lymph node metastasis . After a median follow-up of 56 months, 78 patients had normal calcitonin, 11 patients had biochemical relapse, 3 patients had structural relapse, and no patients died. 57 cases had a higher calcitonin ,median tumor size (1.97±1.22)cm, 46 cases had lymph node metastasis, 5 cases had distant metastasis, 18 cases had structural recurrence, and 7 patients died. Univariate analysis showed that lymph node metastasis, TNM stage, preoperative calcitonin, lymph node dissection and postoperative calcitonin were correlated with long-term disease-free survival (all P < 0.05). Multivariate analysis showed that postoperative calcitonin and TNM stage were an independent prognosis factor for disease-free survival in MTC patients (all P < 0.05). Conclusion:Postoperative calcitonin is a independent prognostic marker for long-term disease-free survival in MTC patients.

Objective:This study aimed to investigate the risk features of postoperative tumor recurrence of medullary thyroid carcinoma.Methods:One hundred and seventy two patients with medullary thyroid carcinoma diagnosed at Tianjin Cancer Hospital between Jan 2010 and Jan 2018 were enrolled in this study. Based on the follow-up results, patients were divided into tumor recurrence and non-tumor recurrence group. US features,clinicopathological characteristics and somatic RET mutations were evaluated between the two groups. The cut-off values of pre-and post-operative serum calcitonin were calculated by ROC curve.Univariate and multivariate analysis were adopted between the two groups to determine independent risk factors for tumor recurrence of MTC.Tumor-free survival was determined by Kaplan-Meier analysis.Results:Univariate analysis showed that preoperative serum calcitonin≥1 367 pg/ml ( χ2=18.909, P=0.000), postoperative serum calcitonin ≥61 pg/ml ( χ2=72.278, P=0.000), mulifocality ( χ2=11.787, P=0.001),lesions in both lobes ( χ2=10.452, P=0.003), extrathyroidal invasion ( χ2=14.511, P=0.000), T3+T4-staging ( χ2=11.920, P=0.001)、TNMⅢ+Ⅳ-staging ( χ2=18.915, P=0.000), ACR TI-RADS 5 ( χ2=7.162, P=0.006) and RET mutation ( χ2=10.937, P=0.001) were significantly related to tumor recurrence of medullary thyroid carcinoma. Multivariate analysis demonstrated that postoperative serum calcitonin≥61 pg/ml ( OR=22.323, 95%CI: 6.370-78.236) and RET mutation ( OR=4.054, 95%CI: 1.354-12.139) were the independent factors related to tumor recurrence of medullary thyroid carcinoma.The survival curves of MTC patients showed a significantly lower percentage of surviving patients in the group with postoperative serum calcitonin ≥61 pg/ml ( P=0.000) or RET mutations ( P=0.001). Conclusions:Postoperative serum calcitonin ≥61 pg/ml and oncogenic RET mutation were the independent risk factors for tumor recurrence of MTC.Patients with postoperative serum calcitonin ≥61 pg/ml or a RET mutation tended to have a shorter tumor-free survival.

Objective:To compare the prognosis of patients with unilateral sporadic medullary thyroid carcinoma treated by different surgical selection, and analyze the independent risk factors affecting the prognosis.Methods:One hundred and twenty-six patients at Tianjin Medical University Cancer Institute and Hospital from Feb 2011 to Oct 2018 were retrospectively divided into group A (total thyroiclectomy) and group B (unilateral lobectomy).Results:There were no significant differences in postoperative recurrence rate ( χ2=0.394, P=0.530), mortality ( χ2=3.175, P=0.146), biochemical cure rate ( χ2=0.613, P=0.434), progression free survival and overall survival ( P=0.278, 0.175) between group A and group B; Tumor diameter ≥4 cm and lateral cervical lymph node metastasis were independent risk factors affecting the overall survival. The incidence of postoperative temporary hypocalcemia ( χ2=5.068, P=0.024) and permanent hypocalcemia ( χ2=6.590, P=0.010) in group A was higher than that in group B. Conclusions:Ipsolateral thyroidectomy can be applied to patients with unilateral sporadic medullary thyroid carcinoma with similar long term prognosis and tower incidence of temporary hypocalcemia and permanent hypocalcemia compared to total thyroidectomy.

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.

Head and neck squamous cell carcinoma (HNSCC), as the most common type (>90%) of head and neck cancer, includes various epithelial malignancies that arise in the nasal cavity, oral cavity, pharynx, and larynx. In 2020, approximately 878 ‍ 000 new cases and 444 000 deaths linked to HNSCC occurred worldwide (Sung et al., 2021). Due to the associated frequent recurrence and metastasis, HNSCC patients have poor prognosis with a five-year survival rate of 40%-50% (Jou and Hess, 2017). Therefore, novel prognostic biomarkers need to be developed to identify high-risk HNSCC patients and improve their disease outcomes.
Biomarkers, Tumor/genetics* ; Head and Neck Neoplasms/genetics* ; Humans ; Kaplan-Meier Estimate ; RNA ; Squamous Cell Carcinoma of Head and Neck ; Survival Analysis ; Survival Rate