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.

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.

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.

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.

Animals ; Apoptosis ; Endotoxins/toxicity* ; Heart/drug effects* ; MAP Kinase Signaling System ; Myocardium/pathology* ; Rats ; Rats, Wistar ; Receptors, Calcium-Sensing/metabolism*

Objective:To explore the blood pressure levels and the influencing factors of hypertension among Hainan centenarians, and provide basic data for the further blood pressure related studies of the centenarian population.Methods:The baseline data were from China Hainan Centenarian Cohort Study (CHCCS). This cross-sectional data, based on the community population, was a complete sample study of centenarians, including questionnaire survey, physical examination and physiological index detection. A total of 1 002 centenarians were recruited to describe the blood pressure level. According to the guidelines for the prevention and treatment of hypertension in Chinese adults in 2018, the prevalence of hypertension was analyzed.Results:The median levels of systolic blood pressure, diastolic pressure and pulse pressure were 152.0, 76.0 and 76.5 mmHg, respectively. Blood pressure level was higher in females than in males. The prevalence of hypertension was 71.9%, mainly in isolated systolic hypertension with the prevalence of 60.1%. The results of multivariate analysis showed that the risk of hypertension in women was higher than that in men ( OR=1.624, 95% CI: 1.155-2.283), and the risk of hypertension in the northern ( OR=0.625, 95% CI: 0.434-0.901) and central areas ( OR=0.586, 95% CI: 0.346-0.993) was lower than that of the Eastern. Conclusion:The prevalence of hypertension, mainly in isolated systolic hypertension, showing gender and regional distribution differences.

Non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancer, with a 5-year survival rate of less than 15%-19%, and more than 80% of the patients with lung cancer have progressed to advanced stage (Stage IIIb-IV) when they are clearly diagnosed. The comprehensive treatment mainly based on chemotherapy as the primary form is now considered as the major therapy method for advanced NSCLC without actionable driver gene mutations. Pemetrexed plus platinum doublet as well as single-agent pemetrexed are respectively the first-line major regimens recommended by guidelines and the second-line optional regimens. Yet the third-line treatment or beyond in advanced NSCLC is not evidence-based but conducted based on patients' previous medications, which is one of the most commonly used clinical methods. As pemetrexed is a multi-target chemotherapy drug with high efficiency but low toxicity, pemetrexed re-challenge strategy in advanced NSCLC is also a reasonable choice. We report one effective individual case that adopted pemetrexed re-challenge strategy in advanced NSCLC for three times, and at the same time conduct the relevant literature review.
Carcinoma, Non-Small-Cell Lung ; diagnostic imaging ; drug therapy ; Female ; Humans ; Lung Neoplasms ; diagnostic imaging ; drug therapy ; Middle Aged ; Pemetrexed ; administration & dosage ; Positron Emission Tomography Computed Tomography

Objective To explore the value of combined detection with MMP-9 and uPA in the progno-sis of pancreatic carcinoma. Methods By immunohistochemistry PV methods,the expression of MMP-9 and uPA was respectively studied in 63 surgical specimens of primary pancreatic carcinoma and the survival time of patients with pancreatic carcinoma was analysed. Results The expressions of MMP-9 and uPA were positively related(r=0. 573,P=0. 000). The expression of MMP-9 and uPA significantly correlated with differentiation (r= -0. 271,P=0. 032;r= -0. 333,P=0. 008),TNM stages(r= -0. 449,P=0. 000;r= -0. 430,P=0. 000)and lymph node metastasis(r=0. 329,P=0. 009;r=0. 400,P=0. 001),separately. The expression of MMP-9 had also a significant correlation with tumer size(r= -0. 297,P=0. 018)and distant metastasis(r=0. 320,P=0. 011). Univariate analysis identified that tumor size(χ2 =8. 766,P=0. 012),differentiation(χ2 =29. 050,P=0. 000),clinical stage(χ2 =24. 940,P=0. 000),distant metastasis(χ2 =12. 846,P=0. 000), lymph node metastasis(χ2 =15. 457,P=0. 000),MMP-9(χ2 =32. 700,P=0. 000)and uPA(χ2 =41. 495,P=0. 000)were significantly associated with prognosis. Kaplan-Meier survival analysis showed that 1-year survival rate of patients with MMP-9 ( -),uPA ( -)were significantly longer than that of the patients with MMP-9( ﹢),uPA( ﹢),respectively(χ2 =32. 700,P=0. 000;χ2 =41. 495,P=0. 000);1-year survival rate of patients with MMP-9( -)/uPA( -)was significantly longer than the others( Log-rank test,χ2 = 54. 892, P=0. 000). COX regression revealed that differentiation(RR=2. 315,P=0. 004),clinical stage(RR=1. 694, P=0. 002),MMP-9(RR=0. 165,P=0. 000)and uPA(RR=0. 244,P=0. 007)was independent prognostic factors in pancreatic carcinoma. Conclusion They may have a synergistic function in the the process of growth and invasion in pancreatic cancer between MMP-9 and uPA,and the posssible mechanism is that uPA activate degradation of MMP-9,which is not favorable to prognosis. Combined analysis of MMP-9 and uPA may lead to a more reliable prognostic estimation,as the beneficial supplement of the differentiation,and clinical stage to judge the prognosis of pancreatic cancer.

OBJECTIVETo report on clinical, genetic and molecular characterization of two Chinese families with Leber's hereditary optic neuropathy.

METHODSOphthalmological examinations have revealed variable severity and age at onset of visual loss among the probands and other matrilineal relatives of both families. The entire mitochondrial genome of the two probands was amplified with PCR in 24 overlapping fragments using sets of oligonucleotide primers.

RESULTSThe ophthalmological examinations showed that penetrance was 12.5% and 30.0% respectively in the two families. Sequence analysis of the complete mitochondrial genomes in these pedigrees has identified unreported homoplasmic T8821G mutation in the ATPase 6 gene and distinct sets of polymorphisms belonging to haplogroups M10a. The T8821G mutation has occurred at the extremely conserved nucleotide (conventional position 99) of the ATPase6. Thus, this mutation may alter structural formation of ATPase6, thereby leading to failure in the synthesis of ATP involved in visual impairment.

CONCLUSIONAbove observations have suggested that the ATPase6 T8821G mutation may be involved in the pathogenesis of optic neuropathy in these families.

Adolescent ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; DNA, Mitochondrial ; genetics ; Female ; Humans ; Male ; Mitochondrial Proton-Translocating ATPases ; genetics ; Molecular Sequence Data ; Optic Atrophy, Hereditary, Leber ; enzymology ; genetics ; Pedigree ; Point Mutation ; Young Adult

Objective To study the expressions of S100A4 and urokinase plasminogen activator(uPA) in pancreatic cancer cells and their correlation with patients prognosis.Methods The expressions of S100A4 and uPA were examined in 63 surgical specimens of primary pancreatic carcinoma by suing immunohistochemistry PV methods,and correlation of their expressions and prognosis of pancreatic cancer was analyzed.Results ( 1 ) Positive immunostaining for S100A4 and uPA was observed in 74.6％ (47 cases) and 65.1％ (44 cases) of 63 pancreatic cancer samples respectively.(2) The positive expressions of S100A4 and uPA were significantly correlated in pancreatic cancer( P =0.000,r =0.567 ).( 3 ) The expression of S100A4 significantly correlated with TNM stages( P =0.002 ),lymph node metastasis ( P =0.002 ) and distant metastasis ( P =0.007 ).The expression of uPA had a significant correlation with TNM stages ( P =0.002),lymph node metastasis ( P =0.001 )and differentiation(P =0.003).(4) Kaplan-Meier survival analysis showed that the median survival (21 months) of patients with S100A4 ( - ) was significantly longer than the median survival ( 9 months) of the patients with S100A4( + )(P=0.000) ;the median survival(9 months) of patients with uPA( + ) was significantly shorter than the median survival ( 18 months) of the patients with uPA ( - ) ( P =0.000) ; the median survival(23 months)of 13 patients with S100A4( - )/uPA( - )was significantly longer than the median survival of other cases ( Log-rank test,x2 =54.444,P =0.000).( 5 ) Cox regression model ( x2 =53.974,P =0.000 )analysis suggested:the differentiation(P =0.004),lymph node metastasis(P =0.017) 、S100A4( + ) expression ( P =0.000) and uPA ( + ) expression ( P =0.001 ) were independent prognostic factors for pancreatic cancer.Conclusion S100A4 and uPA are highly expressed in pancreatic cancer cells,and S100A4 expression has positive correlation with uPA expression,which indicates that the overexpression of S100A4 and uPA maybe poor prognosis factors for pancreatic cancer patients.S100A4 maybe promote extracellular matrix and basement membrane degradation by up-regulation of uPA protein expression,and ultimately promote tumor invasion and metastasis,which is not favorable to prognosis.They may be potential indicators of metastasis and predictors for prognosis of pancreatic cancer.