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.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.
3.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.
4.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;(12):794-798
Objective To study the prevalence of the BRAF V600E mutation in papillary thyroid carcinoma ( PTC) and its association with clinicopathologic features.Methods Two 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 theχ2 test or Fisher exact test as appropriate.Results There 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).Conclusion BRAF 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.
5.Construction of transitional care evaluation system for lung cancer patients with chemotherapy based on Omaha system
Lijun LIN ; Yimin LI ; Li WANG ; Li NING ; Yafen YUAN ; Haizhen GUO
Chinese Journal of Modern Nursing 2020;26(19):2550-2556
Objective:To construct transitional care evaluation system for lung cancer patients with chemotherapy based on Omaha systemtheory.Methods:Based on literature research, the first draft of transitional care evaluation system for lung cancer patients with chemotherapy was preliminarily formulated by combining Omaha system, content analysis, cross-mapping method and expert group meeting. By using Delphi expert consultation method, 15 experts from the field of oncology medicine and oncology nursing were conducted two rounds of expert consultation from January 2019 to March 2019. Finally, the transitional care evaluation system for lung cancer patients with chemotherapy was formed. From April 2019 to May 2019, 30 lung cancer patients with chemotherapy in a cancer specialist hospital were selected to evaluate the importance of the contents of the transitional care nursing evaluation system. The enthusiasm of experts was expressed by the effective recovery rate of the questionnaire, the authority of experts was expressed by the expert authority coefficient ( Cr) , the coordination degree of expert opinions was expressed by the coefficient of variation and Kendall coordination coefficient, and the concentration degree of opinions was expressed by the value of importance. Results:The recovery rates of the two rounds of expert consultation questionnaires were 100%. The expert authority coefficient of the second round of expert consultation was 0.80. Kendall's coordination coefficients of the first-levelindicators and second indicators were 0.300 and 0.160 respectively ( P<0.001) . The evaluation opinions of experts and patients tended to be consistent. The transitional care evaluation system for lung cancer patients with chemotherapy was finally constructed, including 8 first-level indicators and 62 second-level indicators. Conclusions:In this study, contents of transitional care evaluation system for lung cancer patients with chemotherapy are scientific and reasonable, which can provide a reference for the effective implementation of transitional care for lung cancer patients with chemotherapy.
6.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.
7.Design and Construction of a Specialized Clinical Research Database for Inflammatory Demyelinating Diseases of the Central Nervous System
Lei WU ; Bing WANG ; Qian YU ; Hui SUN ; He ZHAO ; Sai GAO ; Hena GUO ; Yanning HUANG ; Zhaoyou MENG ; Li-Anchen XIAO ; Haizhen XU ; Dehui HUANG
Journal of Medical Informatics 2024;45(5):83-88
Purpose/Significance To construct a specialized database for inflammatory demyelinating disease of the central nervous system(CNS),so as to contribute to clinical research and improve the diagnostic and treatment capabilities of primary healthcare institu-tions.Method/Process Using the internet to collect medical data,after processing and analysis,the CNS inflammatory demyelinating disease database is constructed.Using statistical analysis,natural language processing(NLP),artificial intelligence(AI)image recog-nition and data visualization and other technologies,the database information is integrated and analyzed.Result/Conclusion A standard-ized big database for CNS inflammatory demyelinating diseases is constructed,which enables visualization of clinical research data,pro-vides patient education and specialist training,and facilitates multi-center teleconsultations.The establishment of a specialized database for the CNS inflammatory demyelinating disease can promote the transformation of medical research achievements,provide references for future real-world clinical research,optimize the process of diagnosis and treatment,and improve the clinical capability of primary healthcare institutions.
8.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
9.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.
10.The efficacy and safety of immunotherapy combined with chemotherapy neoadjuvant in locally advanced resectable hypopharyngeal squamous cell carcinoma
Kai WANG ; Wei ZHANG ; Lin GUI ; Xiaohui HE ; Jingbo WANG ; Haizhen LU ; Dezhi LI ; Chang LIU ; Zizhao GUO ; Meng XU ; Shaoyan LIU ; Xiaolei WANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2024;59(4):343-349
Objective:To explore the efficacy and safety of immunoneoadjuvant therapy with pembrolizumab combined with chemotherapy in locally advanced resectable hypopharyngeal squamous cell carcinoma patients.Methods:This study was a prospective, single arm, single center clinical study that was opened for enrollment in April 2021. Patients who met the inclusion criteria at the Cancer Hospital of the Chinese Academy of Medical Sciences were treated with neoadjuvant therapy of pembrolizumab combined with cisplatin and paclitaxel, and after treatments, received surgery and postoperative adjuvant therapy. The main endpoint of this study was postoperative pathological complete response (pCR), and other observations included adverse reactions and long-term prognoses of patients after neoadjuvant therapy.Results:By September 2023, a total of 23 patients who underwent neoadjuvant therapy and surgery were enrolled in the study and all patients were males aged 49-74 years. All patients were locally advanced stage, including 3 patients in stage Ⅲ and 20 patients in stage Ⅳ. There were 12 cases of primary lesions with posterior ring involvement accompanied by fixation of one vocal cord and 20 cases of regional lymph node metastases classified as N2. Eighteen cases received a two cycle regimen and 5 cases received a three cycle regimen for neoadjuvant therapy. The postoperative pCR rate was 26.1% (6/23), with no surgical delay caused by adverse drug reactions. The laryngeal preservation rate was 87.0% (20/23). Pharyngeal fistula was the main surgical complication, with an incidence of 21.7% (5/23). The median follow-up time was 15 months, and 3 patients experienced local recurrence.Conclusions:The immunoneoadjuvant therapy of pembrolizumab combined with chemotherapy has a high pCR rate in locally advanced resectable hypopharyngeal squamous cell carcinoma, with increased laryngeal preservation rate and no significant impact on surgical safety.