1.Analysis of the expression changes of immune-related cells and cytokines in papillary thyroid carcinoma
Fuxin LI ; Cangchang SHI ; Lanning JIA ; Zhufeng LI ; Xianghui HE
Chinese Journal of Endocrine Surgery 2025;19(4):521-526
Objective:To analyze the relationship between tumor-associated immune cells and cytokines with papillary thyroid carcinoma (PTC) and explore the correlation between tumor-associated immune cells and the risk stratification of PTC recurrence.Methods:A total of 58 PTC patients diagnosed by surgical pathology from Aug. 2022 to Aug. 2023 in the General Surgery and Thyroid and Hernia Department of Tianjin Medical University General Hospital were selected. All patients underwent thyroidectomy combined with central or lateral cervical lymph node dissection. According to lymph node metastasis status, patients were divided into lymph node metastasis-negative (22 cases) and lymph node metastasis-positive groups (36 cases) based on post-operative pathological diagnosis. Flow cytometry was used to detect the levels of tumor-associated immune cells (T, B, NK cells) and cytokines (IL-10, IL-17, IL-35, IFN-γ) in T cells.Results:Compared to normal tissue located distant from the cancer, a significant increase in the proportion of NK cells was observed in cancerous tissue ( t=-2.11, P=0.032). Similarly, the proportion of CD8+ T cells was also significantly elevated ( t=-5.12, P=0.005). In lymph node tissue, the proportion of CD4+ T cells in LNM-positive tissue was significantly higher than in LNM-negative tissue ( t=-3.89, P=0.004), while the proportion of CD8+ T cells exhibited a significant decrease ( t=2.41, P=0.004). Additionally, the levels of IL-10 in cancerous tissue were significantly elevated ( t=-3.83, P=0.003), as were the levels of IL-17 ( t=-4.83, P=0.003). In lymph node tissues categorized by LNM status, although not statistically significant, the levels of IL-10 and IL-17 were generally higher in LNM-positive cases compared to LNM-negative cases. Among the 58 cases stratified by recurrence risk, 22 cases (37.9%) were classified as low-risk, while 36 cases (62.1%) were classified as intermediate-risk. The differences in the proportions of CD4+ T and CD8+ T cell subsets in the lymph nodes of PTC patients were statistically significant. Logistic regression analysis indicated that a higher proportion of CD4+ T cell subsets in the lymph nodes of PTC patients was associated with a higher recurrence risk stratification compared to those with a lower proportion ( OR=1.107, 95% CI: 1.001-1.224). Using the predicted probability as the test variable and "low and medium risk" as the state variable, a ROC curve was constructed, yielding an AUC of 0.790 with P=0.003, indicating a good predictive effect of the model on the dependent variable. Conclusions:Compared to normal tissues located distant from cancerous regions, cancer tissues exhibit a significantly elevated proportion of tumor-associated immune cells and cytokine levels, thereby creating an immunosuppressive tumor microenvironment. Additionally, patients with papillary thyroid carcinoma (PTC) who are classified as having a higher risk of recurrence demonstrate a greater proportion of CD4+ T cell subsets in their lymph nodes.
2.Hyperparathyroidism-jaw tumor syndrome: a case report
Lanning JIA ; Ruoyu JIANG ; Xiaoning WANG ; Ke ZHAO ; Fuxin LI ; Yizeng WANG ; Xianghui HE
Chinese Journal of Endocrine Surgery 2025;19(5):787-789
Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare familial autosomal dominant genetic disease with primary hyperparathyroidism, jaw tumors, kidney tumors and uterine tumors caused by cell division cycle 73 (CDC73) germline mutations. A 42-year-old male patient was admitted for pancreatitis and further examination revealed elevated PTH at 54.00pmol/L and a history of jaw tumors. This patient was diagnosed as HPT-JT finally and underwent upper right, lower right, and upper left parathyroid glands resection and genetic testing. Postoperative pathology revealed that atypical adenomatous nodules of parathyroid glands with extensive atypia and nucleus division and parathyroid hyperplasia and whole exome sequencing suggested that the CDC73 mutation.
3.Analysis of the expression changes of immune-related cells and cytokines in papillary thyroid carcinoma
Fuxin LI ; Cangchang SHI ; Lanning JIA ; Zhufeng LI ; Xianghui HE
Chinese Journal of Endocrine Surgery 2025;19(4):521-526
Objective:To analyze the relationship between tumor-associated immune cells and cytokines with papillary thyroid carcinoma (PTC) and explore the correlation between tumor-associated immune cells and the risk stratification of PTC recurrence.Methods:A total of 58 PTC patients diagnosed by surgical pathology from Aug. 2022 to Aug. 2023 in the General Surgery and Thyroid and Hernia Department of Tianjin Medical University General Hospital were selected. All patients underwent thyroidectomy combined with central or lateral cervical lymph node dissection. According to lymph node metastasis status, patients were divided into lymph node metastasis-negative (22 cases) and lymph node metastasis-positive groups (36 cases) based on post-operative pathological diagnosis. Flow cytometry was used to detect the levels of tumor-associated immune cells (T, B, NK cells) and cytokines (IL-10, IL-17, IL-35, IFN-γ) in T cells.Results:Compared to normal tissue located distant from the cancer, a significant increase in the proportion of NK cells was observed in cancerous tissue ( t=-2.11, P=0.032). Similarly, the proportion of CD8+ T cells was also significantly elevated ( t=-5.12, P=0.005). In lymph node tissue, the proportion of CD4+ T cells in LNM-positive tissue was significantly higher than in LNM-negative tissue ( t=-3.89, P=0.004), while the proportion of CD8+ T cells exhibited a significant decrease ( t=2.41, P=0.004). Additionally, the levels of IL-10 in cancerous tissue were significantly elevated ( t=-3.83, P=0.003), as were the levels of IL-17 ( t=-4.83, P=0.003). In lymph node tissues categorized by LNM status, although not statistically significant, the levels of IL-10 and IL-17 were generally higher in LNM-positive cases compared to LNM-negative cases. Among the 58 cases stratified by recurrence risk, 22 cases (37.9%) were classified as low-risk, while 36 cases (62.1%) were classified as intermediate-risk. The differences in the proportions of CD4+ T and CD8+ T cell subsets in the lymph nodes of PTC patients were statistically significant. Logistic regression analysis indicated that a higher proportion of CD4+ T cell subsets in the lymph nodes of PTC patients was associated with a higher recurrence risk stratification compared to those with a lower proportion ( OR=1.107, 95% CI: 1.001-1.224). Using the predicted probability as the test variable and "low and medium risk" as the state variable, a ROC curve was constructed, yielding an AUC of 0.790 with P=0.003, indicating a good predictive effect of the model on the dependent variable. Conclusions:Compared to normal tissues located distant from cancerous regions, cancer tissues exhibit a significantly elevated proportion of tumor-associated immune cells and cytokine levels, thereby creating an immunosuppressive tumor microenvironment. Additionally, patients with papillary thyroid carcinoma (PTC) who are classified as having a higher risk of recurrence demonstrate a greater proportion of CD4+ T cell subsets in their lymph nodes.
4.Hyperparathyroidism-jaw tumor syndrome: a case report
Lanning JIA ; Ruoyu JIANG ; Xiaoning WANG ; Ke ZHAO ; Fuxin LI ; Yizeng WANG ; Xianghui HE
Chinese Journal of Endocrine Surgery 2025;19(5):787-789
Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare familial autosomal dominant genetic disease with primary hyperparathyroidism, jaw tumors, kidney tumors and uterine tumors caused by cell division cycle 73 (CDC73) germline mutations. A 42-year-old male patient was admitted for pancreatitis and further examination revealed elevated PTH at 54.00pmol/L and a history of jaw tumors. This patient was diagnosed as HPT-JT finally and underwent upper right, lower right, and upper left parathyroid glands resection and genetic testing. Postoperative pathology revealed that atypical adenomatous nodules of parathyroid glands with extensive atypia and nucleus division and parathyroid hyperplasia and whole exome sequencing suggested that the CDC73 mutation.
5.Department of Clinicopathological analysis of papillary thyroid carcinoma with Hashimoto’s thyroiditis
Zhigang TIAN ; Li CHEN ; Ziyu LIU ; Yuting LE ; Lanning JIA ; Yue HAN ; Xianghui HE
Chinese Journal of Endocrine Surgery 2023;17(1):24-28
Objective:To discuss the effect of Hashimoto’s thyroiditis (HT) on papillary thyroid carcinoma (РТС) .Methods:The clinical features and pathological characteristics of 682 patients who underwent surgical treatment for the first time from Sep. 1st,2019 to May. 1st, 2021 in Department of Thyroid, Breast and Hernia Surgery, and confirmed by postoperative pathology as papillary thyroid carcinoma were retrospectively analyzed. There were 189 male patients, and 493 female patients, 529 patients < 55 years old and 153 patients ≥55 years old. 476 patients were classified as PTC group and 206 patients as PTC combined with HT group. Chi square test was used to compare the difference between two groups in gender, age, thyroglobulin antibody, thyroid stimulating hormone, thyroid peroxidase antibodies, thyroid peroxidase, number of lesions, metastasis lymph node in central region, thyroid stimulating hormone receptor antibody, carcinoembryonic antigen, whether microcarcinoma, vascular invasion, glandular outside violation, capsule and lateral transfer analysis, ultrasonic calcification, etc. At the same time, all patients were divided into the group without central lymph node metastasis (345 cases) and the group with central lymph node metastasis (337 cases) . The χ 2 test was used to compare the differences between the two groups in terms of sex, age, number of lesions, microcarcinoma, vascular invasion, extradular invasion, capsular invasion, lateral cervical lymph node metastasis, ultrasonic calcification and so on, so as to analyze the differences in clinical characteristics between the two groups. Results:There were 206 cases (30.21%) in PTC combined with HT group and 476 cases (69.79%) in PTC without HT group. There were significant differences in gender (12/194 vs 177/299) ( P=0.000) , age (175/31 vs 354/122) ( P=0.002) , TgAb (115/91 vs 455/21) ( P=0.000) ,TSH (13/175/18 vs 33/429/14) ( P=0.004) , TPOAb (90/116 vs 422/54) ( P=0.000) , number of lesions (114/92 vs 325/151) ( P=0.001) and lymph node metastasis in central area (87/119 vs 250/226) ( P=0.014) between the two groups ( P < 0.05) , but there were no significant differences in TRAb (196/10 vs 461/15) ( P=0.171) , CEA (205/1 vs 469/7) ( P=0.478) , microcarcinoma (136/70 vs 309/167) ( P=0.781) , vascular invasion (4/202 vs 16/460) ( P=0.446) , extraglandular invasion (52/154 vs 108/368) ( P=0.470) , capsule invasion (149/57 vs 358/118) ( P=0.429) , lateral neck lymph node metastasis (31/175 vs 72/404) ( P=0.979) or ultrasonic calcification (157/49 vs 392/84) ( P=0.063) . Compared with PTC group, PTC combined with HT group had the characteristics of more women, younger age, high TgAb, high TSH, high TPOAb, multiple lesions and high proportion of non central lymph node metastasis. There were 345 cases (50.59%) without central lymph node metastasis and 337 cases (49.41%) with central lymph node metastasis. Gender (71/274 vs 118/219) ( P=0.000) , age (246/99 vs 283/54) ( P=0.000) , exadular invasion (66/279 vs 94/243) ( P=0.007) , number of lesions (240/105 vs 199/138) ( P=0.004) , microcarcinoma (259/86 vs 186/151) ( P=0.000) , calcification on ultrasound (250/95 vs 299/38) ( P=0.000) , and HT (119/226 vs 87/250) ) ( P=0.014) had statistical significance ( P<0.05) but had no statistical significance in capsule invasion (250/95 vs 257/80) ( P=0.256) or vascular invasion (10/335 vs 10/327) ( P=0.958) . In addition, patients in the group with central lymph node metastasis were more male, younger, with multiple lesions, exadenocarcinoma, less microcarcinoma, and calcification on ultrasound without hashimoto. Univariate analysis showed that gender, age, number of lesions, extraglandular invasion, calcification, microcarcinoma and Hashimoto had significant effects on lymph node metastasis in the central region; Multivariate analysis showed that the presence of microcarcinoma, ultrasonic calcification, Hashimoto and the number of lesions were independent risk factors for central lymph node metastasis. Conclusion:HT may promote the occurrence of PTC, but at the same time inhibit its development, so that PC patients with HT have a better prognosis.
6.Ferroptosis-related gene and its relationship with prognosis of differentiated thyroid carcinoma patients
Yue HAN ; Zuoyu CHEN ; Lanning JIA ; Xianghui HE
Chinese Journal of Endocrine Surgery 2022;16(4):411-415
Objective:To analyze the marker of ferroptosis-related genes in differentiated thyroid carcinoma (DTC) based on TCGA database.Methods:The mRNA expression profiles and survival information of thyroid cancer patients and normal thyroid samples were downloaded from the TCGA database. The genetic difference analysis added 653 normal thyroid samples from the GETx database. Twenty-two ferroptosis-related genes were selected for univariate Cox regression analysis. Genes associated with prognostic in the TCGA cohort were further screened and prognostic models using LASSO regression was constructed. Adjusted P<0.05 and | log2FC>1" as the threshold, 22 differentially expressed genes were selected. The genes were screened by multivariate Cox regression analysis for prognosis-related genes and displayed in a line diagram. Results:22 of the 24 ferroptosis-related genes were differentially expressed between the tumor and normal tissues, with13 high expression, 9 low expression, 1 gene expression without difference and 1 gene not expressed in half of the samples. Univariate Cox regression analysis found that DPP4 and TFRC were associated with the degree of disease risk (HR was<1 and>1, respectively) . When integrating GPX4, TFRC and DPP4 into the LASSO model screening, it was found to be related to prognosis after dividing the patients into risk groups according to lambda. min=0.0027, Riskscore= (0.7316) * TFRC+ (-0.2539) *DPP4 (Log rank P=0.00635. Multivariate Cox regression analysis found that DPP4 and TFRC were related to the degree of disease risk (HR were<1 and>1, respectively) . Conclusion:The model of TFRC and DPP4 constructed by ferroptosis-related differential expression genes may be potential predictive markers of DTC patients, which still needs further verification and will provide theoretical basis for further clinical treatment.
7.Effect of annexin A1 on the proliferation, migration and invasion of papillary thyroid carcinoma
Li CHEN ; Zhigang TIAN ; Lanning JIA ; Yang YANG ; Ke ZHAO ; Yizeng WANG ; Xianghui HE
Chinese Journal of Endocrine Surgery 2022;16(1):23-27
Objective:To investigate the effect of ANXA on biological behavior of papillary thyroid carcinoma (PTC) cells by interfering with the expression of annexin A1 (ANXA1) in PTC cell lines by short hairpin RNA (shRNA) .Methods:The shRNA with specific and high efficiency was designed to specifically interfere with the expression of ANXA1 in TPC-1 and BCPAP cell lines, and transfect the TPC-1 and BCPAP cell lines respectively, including specific ANXA1 interference and negative control virus transfection, and they were divided into shANXA1 group and negative control virus group. Semi-quantitative reverse transcription PCR (Q-PCR) and Western Blot were employed to verify gene expression. The shANXA1 group was used as the experimental group, the untransfected virus group and the negative control virus group were set as the control groups. The expression levels of ANXA1 in the three groups were compared and the shRNA interference efficiency was verified. The effects of ANXA1 knockdown on the proliferation, migration and invasion of TPC-1 and BCPAP cell lines were investigated by scratch, CCK8 and Transwell invasion experiments. Independent sample t test was used to compare the means between the two groups, and one-way analysis of variance was employed to compare multiple groups, with P<0.05 as statistically significant. Results:shRNA could efficiently silence the expression of ANXA1 at the transcription and translation level in PTC cell lines. Compared with the negative control cells, the cells proliferated after successful lentiviral transfection of TPC-1 and BCPAP (BCPAP, 24h: F= 25.15, P<0.001; 48h: F=6.44, P<0.001; 48h: F=46.94, P<0.001; TPC-1, 24h: F=207.50, P<0.001; 48h: F=202.45, P<0.001; 48h: F=55.89, P<0.001) , its migration (BCPAP, F=12511.10, P<0.001; TPC-1, F=3966.10, P<0.001) and invasion ability (BC-PAP: F=94.65, P<0.001; TPC-1: F=681.74, P<0.001) significantly decreased. Conclusion:After shRNA knock-down of ANXA1 gene, the proliferation, migration and invasion ability of TPC-1 and BCPAP cell lines decreased significantly, indicating that silencing this gene can reduce tumor aggressiveness, and initially reveals that ANXA1 may be an important potential in PTC biotherapy Target.
8.One case of recurrent parathyroid carcinoma complicated with lung metastasis after parathyroid adenoma operation and literature review
Zhigang TIAN ; Zipeng XIE ; Li CHEN ; Ziyu LIU ; Yuting LE ; Lanning JIA ; Yue HAN ; Xianghui HE
Chinese Journal of Endocrine Surgery 2022;16(2):253-254
This paper reports the clinical data of a patient with recurrent metastatic parathyroid carcinoma. The causes, clinical manifestation, diagnose, treatment and prognosis of parathyroid carcinoma were discussed in order to perfect the experience of diagnosis and treatment and improve the survival rate of such patients.
9.Meta-analysis of the clinical effect and safety of bevacizumab combined with FOLFOX in patients with advanced colorectal cancer
Wenlong DU ; Jia WANG ; Yuanxian GUO ; Xiaoping YANG ; Lanning YIN
International Journal of Surgery 2020;47(4):245-251,289-290
Objective:To systematically evaluate the clinical effect and safety of bevacizumab combined with FOLFOX regimen in patients with advanced colorectal cancer.Methods:An electronic search of Pubmed, Embase, CNKI and other Chinese and English databases were retried from their inception to December 2018 to identify relevant literatures, by taking "Bevacizumab, FOLFOX, Advanced Colorectal Cancer, Randomized Controlled Trial" as the keywords for retrieval. Patients were divided into a combination group (bevacizumab combined with FOLFOX program) and a control group (using FOLFOX program alone) according to the treatment method, using Revman 5.3 software for meta-analysis.Results:A total of 11 articles, involving 3178 patients, were included with 1599 in the combination group and 1579 in the control group. The objective group response rate ( OR=3.15, 95% CI: 2.25 ~ 4.40, Z=6.71, P<0.000 01) and disease control rate ( OR=2.73, 95% CI: 1.91 ~ 3.90, Z=5.49, P<0.000 1) in combination group were higher than those in the control group. In terms of adverse reactions, the incidence of gastrointestinal reactions in the combination group was higher than that in the control group ( OR=1.29, 95% CI: 1.07~1.55, Z=2.64, P=0.008 ), There was no significant difference in the incidence of liver injury, leukopenia, hypertension, and neurotoxicity between the two groups. Conclusion:Bevacizumab combined with FOLFOX regimen is more effective than FOLFOX regimen for patients with advanced colorectal cancer, but it will increase the risk of gastrointestinal reactions.

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