1.Risk factors of central lymph node metastasis in patients with thyroid micropapillary carcinoma complicated with Hashimoto thyroiditis
Jifan WANG ; Zhongwei CAO ; Haizhen BAI ; Ruiyu GUO
International Journal of Surgery 2023;50(1):44-49,C3
Objective:To explore the risk factors of central lymph node metastasis (CLNM) in Hashimoto thyroiditis (HT) patients with thyroid micropapillary carcinoma (PTMC), and formulate a reasonable range of lymph node.Methods:Retrospective analysis of 448 cases of PTMC admitted to the People′s Hospital of Inner Mongolia Autonomous Region from September 2018 to September 2021 including 94 males and 354 females, with a male female ratio of 1.00∶3.77, all patients aged 21 to 82 years old, with the average of (46.9 ± 11.0) years old. According to whether Hashimoto thyroiditis (HT) is combined, it is divided into HT-PTMC group ( n=142) and non HT-PTMC group ( n=306).Single factor analysis and multiple factor analysis were used to explore whether the clinicopathological characteristics of patients such as gender, age, tumor diameter, number of lesions (single/multiple lesions), presence of capsule invasion, pretracheal/paratracheal lymph nodes, delphian lymph nodes, and lateral cervical lymph nodes were related to lymph node metastasis in the central region. SPSS 20.0 software was used for statistical analysis and logistic regression equation was established, The mathematical model was used to evaluate the predictive value of diagnosis and treatment. Results:There were significant differences between HT-PTMC group and non HT-PTMC group in terms of age, sex, metastasis of anterior laryngeal lymph nodes and lateral cervical lymph nodes ( P<0.05). Univariate analysis showed that tumor diameter, number of lesions, capsule invasion, calcification, lateral cervical lymph node metastasis were correlated with CLNM in HT-PTMC patients ( P<0.05). Multivariate logistic regression analysis showed that tumor diameter increase and capsule invasion were independent risk factors for CLNM ( P<0.05). Logistic regression mathematical model was established according to the above independent risk factors: (Y=-1.974+ 0.191 × Tumor diameter+ 1.139 × The area under the ROC curve for predicting CLNM in HT-PTMC patients was 0.669 (95% CI: 0.571- 0.766). When taking the maximum Jordan index, the sensitivity of prediction was 0.460, and the specificity was 0.859. Conclusions:For PTMC patients with HT, there is evidence that the tumor diameter increases or the capsule is invaded, and the risk of lymph node metastasis in the central region is increased. Preventive lymph node dissection in the central region is recommended.
2.Comparison of real-time PCR method with Sanger sequencing for detection of BRAF muta-tion in papillary thyroid carcinoma
Tian QIU ; Wenting HUANG ; Lei GUO ; Haizhen LU ; Yun LING ; Ling SHAN ; Wenbin LI ; Ning Lü ; Jianming YING
Chinese Journal of Clinical and Experimental Pathology 2015;(7):756-758
Purpose To investigate the positive rate and concordance rate of BRAF mutation in papillary thyroid carcinoma detected by real-time PCR method and Sanger sequencing. Methods 312 papillary thyroid carcinomas patients were enrolled in this study. Real-time PCR method and Sanger sequencing were performed to detect BRAF gene mutations. The frequency of BRAF mutation and the concordance of two methods were analyzed. Results BRAF mutation was detected in 65. 4% (204/312) and 63. 8% (199/312) of 312 papillary thyroid carcinoma samples by using real-time PCR method and Sanger sequencing, respectively. There was no significant correlation between BRAF gene mutations and patients’ gender. There was significant correlation between BRAF gene mutations and patients’ age. The overall concordance between real-time PCR method and Sanger sequencing for BRAF mutation detection was 98. 4%. Conclusion Real-time PCR method provides an effective method in BRAF gene mutation detection.
3.Prokaryotic expression and activity analysis of 5′-methylthioadenosine nucleosidase in Mycobacterium tuberculosis
Haizhen CHEN ; Hua YANG ; Zhongyi HU ; Huansen YANG ; Hui MA ; Shihui GAO ; Qi GUO ; Wenjuan BAI ; Lianhua QIN ; Lianqing LI
Chinese Journal of Microbiology and Immunology 2012;32(7):589-594
Objective To clone and express of Rv0091 encoding protein in Mycobacterium tuberculosis,identify and characterize of the enzyme activities.Methods Construct the Rv0091 prokaryotic expression plasmid,the vector was transformed into E.coli strain BL21trxB.After induced by IPTG,recombinant protein was purified by Ni2+-NTA chromatography and analyzed for purity by SDS-PAGE gels stained with Coomassie Blue.Immunological activity was identified by Western blot.The recombinant protein molecular weight was identified by Mass spectrometry.The enzyme-coupled assay detectes enzyme activity.Results The expression plasmid pET32a-Rv0091 was constructed and expressed in E.coli.BL21trxB,and the optimum expression system was conformed.The purity of the recombinant protein was more than 95%.Western blot analysis confirmed that recombinant protein was one of Mycobacterium tuberculosis proteins.Mass spectrometry identified the relative molecular weight and theoretical molecular weight was basically the same.Enzyme assay showed the recombinant protein able to catalyze the substrate MTA.Enzymatic properties showed that the optimal buffer for the phosphate and Hepes buffer,the poor thermal stability of the enzyme,the optimal temperature of 37℃,optimal pH10-12,when the pH ≤7,the protein denaturation and loss of some vitality.Conclusion The recombinant protein methylthioadenosine nucleosidase(MTAN) was obtained and enzyme activity was detected and plays a key role in the metabolism of Mycobacterium tuberculosis.
4.Progress of programmed death-1/programmed death-ligand 1 inhibitors in treatment of triple-negative breast cancer
Xin LI ; Haizhen BAI ; Yuanfei SHAN ; Jiang XUE ; Gang GUO
Cancer Research and Clinic 2021;33(12):957-960
Breast cancer is the malignant tumor with the highest incidence among women in the worldwide. The triple-negative breast cancer (TNBC) has the strongest immunogenicity. Because of the lack of clear molecular targets, TNBC is a subtype of breast cancer with more difficulties in the treatment and poorer prognosis compared to other breast cancer subtypes. Blocking the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) signaling pathway has been a hot spot of research and treatment of tumors. PD-1/PD-L1 inhibitors provide new treatment options for TNBC. This article reviews the research progress of PD-1/PD-L1 inhibitors alone or in combination with other drugs in treatment of TNBC, intending to provide the theoretical basis for basic or clinical studies.
5.Correlation between BRAF V600E mutation and clinicopathologic features of papillary thyroid carcinoma.
Haizhen LU ; Tian QIU ; Jianming YING ; Changyuan GUO ; Ning LYN
Chinese Journal of Pathology 2014;43(12):794-798
OBJECTIVETo study the prevalence of the BRAF V600E mutation in papillary thyroid carcinoma (PTC) and its association with clinicopathologic features.
METHODSTwo hundred and ninety-two patients with primary PTC encountered during the period from December 2010 to December 2012 and underwent surgery in Cancer Hospital, Chinese Academy of Medical Science were enrolled into the study. Polymerase chain reaction was used to amplify exon 15 of the BRAF gene from paraffin-embedded thyroid tumor specimens, followed by direct sequencing to detect the BRAF V600E mutation. Statistical analysis was performed with SPSS 16.0 for Windows. Association between BRAF mutation and clinicopathologic parameters was tested with the χ(2) test or Fisher exact test as appropriate.
RESULTSThere were 87 males and 205 females in the cohort. The age of patients ranged from 13 to 84 years (mean = 43.1 years). BRAF V600E mutation was found in 190 cases (65.1%). The presence of BRAF V600E mutation correlated with age at diagnosis (older than 45 years), tumor volume (larger than 1 cm), extrathyroidal extension, classic type/tall-cell variant and advanced disease stage (P < 0.05). BRAF V600E mutation did not correlate significantly with gender, multicentricity, lymph node metastasis or anatomic location (P > 0.05).
CONCLUSIONBRAF V600E mutation is associated with high-risk clinicopathologic characteristics in patients with PTC. The BRAF V600E mutation may be a potential prognostic factor in PTC patients.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; Carcinoma ; genetics ; pathology ; Carcinoma, Papillary ; Exons ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Mutation ; Polymerase Chain Reaction ; Proto-Oncogene Proteins B-raf ; genetics ; Thyroid Neoplasms ; genetics ; pathology
6.Effective Components and Antiarrhythmic Mechanisms of Wenxin Granules Based on CMC/UPLC-Q-TOF/MS
Lu YU ; Shule QIAN ; Haizhen GUO ; Yuke ZHAO ; Xiaofeng LI ; Wuxun DU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):124-132
ObjectiveTo employ the effective components and antiarrhythmic mechanism of Wenxin Granules (WXKL) by cell membrane chromatography (CMC) and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), combined with network pharmacology. MethodIn this study, the CMC/UPLC-Q-TOF/MS technique was employed to identify the components in WXKL that could specifically bind to myocardial cell membranes. By utilizing databases such as SwissTarget Prediction and GeneCards, the targets of WXKL's effective components and arrhythmia-related targets were mined. Cytoscape software was used to construct a "component-target-disease" network. Gene ontology(GO) function and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analyses were carried out, and molecular docking of key components and targets was performed. Finally, further verification was conducted through in vivo experiment of rats. ResultA total of 39 effective components were identified in WXKL. These included 13 components derived from Panax notoginseng, 15 components from Codonopsis pilosula, seven components from Glycyrrhizae Radix et Rhizoma, one component from Succinum, one component from Polygonatum odoratum, one component shared by both P. odoratum and C. pilosula, and one component shared by both Panax notoginseng and C. pilosula. Network pharmacology predicted that WXKL had 16 core antiarrhythmic targets and 79 related pathways, mainly involving adrenergic signaling in cardiomyocytes, cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG), calcium signal, cyclic adenosine monophosphate (cAMP), interleukin (IL)-17, mitogen-activated protein kinase (MAPK), and tumor necrosis factor (TNF) signaling pathways. The results of in vivo experiment of rats showed that WXKL significantly improved the expression of β1-adrenergic receptor (β1-AR), cAMP, TNF-α, and calcium voltage-gated channel subunit alpha 1C (CACNA1C). ConclusionWXKL can exert its antiarrhythmic effects through multiple components, multiple targets, and multiple pathways. This study provides a scientific basis for explaining the potential pharmacodynamic substance foundation and mechanism of action of traditional Chinese medicine in treating arrhythmia.