1.Progress in translational research on immunotherapy for osteosarcoma
Fei HU ; Xiaohan CAI ; Rui CHENG ; Shiyu JI ; Jiaxin MIAO ; Yan ZHU ; Guangjian FAN
Journal of Shanghai Jiaotong University(Medical Science) 2024;44(7):814-821
Osteosarcoma is a common primary malignant bone tumor in adolescents and children,characterized by a high recurrence rate and metastasis,making its treatment extremely challenging.Traditional treatment modalities,including surgery,radiation therapy,and chemotherapy,can alleviate symptoms to some extent,but improving long-term survival rates remains a pressing issue.With the continuous development of immunotherapy,breakthroughs have been made in the research of tumor immune microenvironment and the application of immunotherapy in recent years,providing new perspectives and strategies for osteosarcoma treatment.Currently,immunotherapy strategies include tumor vaccines,targeted cytokines,immune checkpoint inhibition,adoptive cell therapy,combination therapy,etc.,significantly enhancing patient immune responses from the aspects of boosting immunity,overcoming immune tolerance,and preventing immune evasion,thereby effectively improving the patients'survival rates and prognosis.This review aims to systematically introduce the immune microenvironment of osteosarcoma and discuss the latest advances in immunotherapy in clinical translational research of osteosarcoma.By deeply understanding the immune characteristics of osteosarcoma and corresponding treatment methods,it is hopeful to provide more effective strategies for personalized treatment,contributing to the improvement of the patients' survival rates and prognosis.
2.PRMT6 promotes the proliferation and migration of breast cancer cells
Yishan HAN ; Ziqi XU ; Mengyu TAO ; Guangjian FAN ; Bo YU
Journal of Shanghai Jiaotong University(Medical Science) 2024;44(8):999-1010
Objective·To examine the expression level of protein arginine methyltransferase 6(PRMT6)in breast carcinoma tissues and to assess its impact on the proliferative and migratory behaviors of breast cancer cells.Methods·The PRMT6 transcriptome sequencing data between 33 tumor tissues and normal tissues from The Cancer Genome Atlas(TCGA)database was analyzed through the R language.The gene expression profile interactive analysis(GEPIA2)online database was used to analyze the difference of PRMT6 expression in normal breast tissues and breast cancer tissues.By using the immunohistochemistry(IHC)data of human normal breast tissues and breast cancer tissues from Human Protein Atlas(HPA)database to analyze the protein expression of PRMT6.IHC was used to detect the expression of PRMT6 in breast cancer tissues and paired para-tumor tissues from 27 clinical samples.After PRMT6 was knocked down with small interfering RNA(siRNA)in MDA-MB-231 and MCF-7 cells,the expression of PRMT6 was detected by qRT-PCR and Western blotting.The proliferation ability of breast cancer cells was measured with cell counting kit-8(CCK-8)assay and colony formation assay.The effect of PRMT6 on the migration ability of breast cancer cells was detected by wound healing assay and Transwell assay.By using the RNA-sequence data from GSE210948 of Gene Expression Omnibus(GEO)database,differentially expressed genes were analyzed in control and low expression groups of PRMT6.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis was performed to reveal the signaling pathways associated with PRMT6.Cell cycle analysis was detected by flow cytometry.The expressions of cyclin D1 and EMT-related proteins(E-cadherin,N-cadherin and Vimentin)were detected by Western blotting after knocking down PRMT6.Results·Bioinformatics analysis and IHC results showed that PRMT6 was highly expressed in breast cancer tissues compared with normal tissues(P=0.000)and para-tumor tissues(P=0.001).qRT-PCR and Western blotting results verified that the siRNA significantly reduced the expression level of PRMT6 in MDA-MB-231 and MCF-7 cell lines compared with the control group(mRNA:P=0.006,P=0.004;P=0.001,P=0.043.Protein:P=0.035,P=0.001;P=0.003,P=0.002).After knocking down PRMT6,the proliferation(P=0.014,P=0.000;P=0.003,P=0.003)and migration(P=0.000,P=0.000;P=0.000,P=0.002)ability of breast cancer cells were inhibited significantly.The KEGG pathway enrichment analysis showed that the expression of PRMT6 affected the cell cycle pathway.After knocking down PRMT6,the expression of cyclin D1 decreased in protein level(P=0.021,P=0.000;P=0.034,P=0.014)and transcription level(P=0.036,P=0.001;P=0.044,P=0.000).Knock down of PRMT6 increased the number of cells in G0/G1 phase(P=0.000;P=0.003)and decreased the number of cells in G2/M phase of the cell cycle.The expression level of E-cadherin increased(P=0.002,P=0.012;P=0.043,P=0.003),while the expression levels of N-cadherin(P=0.004,P=0.041;P=0.032,P=0.034)and Vimentin(P=0.028,P=0.005;P=0.024,P=0.001)decreased in PRMT6 knockdown cells.Conclusion·PRMT6 is highly expressed in breast cancer,which can promote the proliferation and migration of breast cancer cells.
3.Mechanistic study on the promotion of pancreatic cancer progression through upregulation of ZNF143 by dysregulated fatty acid metabolism
Siwei YU ; Ziqi XU ; Mengyu TAO ; Guangjian FAN
Journal of Shanghai Jiaotong University(Medical Science) 2024;44(10):1255-1265
Objective·To identify key genes that may be regulated by fatty acid alteration in pancreatic cancer through tumor transcriptome screening,and to explore the expression of zinc finger protein 143(ZNF143)in pancreatic cancer and its effect on the migration and invasion of pancreatic cancer cells.Methods·The R language was utilized to integrate transcriptome data,including the GSE164760 dataset from the Gene Expression Omnibus(GEO)database,179 pancreatic cancer tissue samples and 4 adjacent non-cancerous tissue samples from The Cancer Genome Atlas(TCGA)database,as well as 167 normal pancreatic tissue samples from the Genotype-Tissue Expression(GTEx)database.We conducted screening and analysis of potential differential genes that may be induced by dysregulation of fatty acid metabolism in pancreatic cancer.After treating pancreatic cancer cells with palmitic acid(PA)and oleic acid(OA)for 24 hours,the mRNA levels of candidate genes were detected by qRT-PCR.According to the median expression level of the screened gene,pancreatic cancer patients in the TCGA database were divided into two groups with high and low expression of ZNF143.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway and Gene Ontology(GO)enrichment analyses were performed for the differential genes of the two groups.siRNA was used to knock down the expression of ZNF143 in pancreatic cancer cells,and the effects on cell migration and invasion were examined by wound healing assay and invasion assay.Western blotting was used to explore the impact of ZNF143 on epithelial mesenchymal transition(EMT)-related proteins and the Wnt/β-catenin pathway.Results·The bioinformatics database was processed to analyze key genes associated with the up-regulation of genes in lipid metabolism disorders in pancreatic cancer and liver cancer.Among them,ZNF143 was a potential gene associated with fatty acid accumulation in pancreatic cancer.In vitro experiments confirmed that the mRNA level of ZNF143 was significantly up-regulated after treating pancreatic cancer cells with palmitic acid or oleic acid.Both KEGG and GO enrichment analyses demonstrated that the differentially expressed genes associated with ZNF143 were predominantly enriched in adhesion pathways.In functional experiments,the migration and invasion abilities of pancreatic cancer cells transfected with ZNF143 siRNA were reduced,and the expression of EMT-related proteins was also decreased,potentially related to the activation of the Wnt/β-catenin pathway.Conclusion·Fatty acid accumulation up-regulates the mRNA expression of ZNF143 in pancreatic cancer cells,and ZNF143 may enhance the migration and invasion of these cells by facilitating EMT through activation of the Wnt/β-catenin pathway.
4.Short-term efficacy and safety of pembrolizumab combined with neoadjuvant chemotherapy for the treatment of non-small cell lung cancer
Yixing LI ; Heng ZHAO ; Bohao LIU ; Jizhao WANG ; Yanpeng ZHANG ; Chendong GUO ; Chuchen ZHAO ; Kun FAN ; Hongyi WANG ; Runyi TAO ; Zhiyu WANG ; Jia ZHANG ; Junke FU ; Guangjian ZHANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(03):369-374
Objective To explore the short-term efficacy and safety of pembrolizumab combined with chemotherapy in the neoadjuvant treatment of non-small cell lung cancer. Methods The clinical data of 11 male patients with non-small cell lung cancer who underwent pembrolizumab combined with neoadjuvant chemotherapy in the Department of Thoracic Surgery, the First Affiliated Hospital of Xi'an Jiaotong University from December 2019 to June 2021 were retrospectively analyzed. The average age of the patients was 52.0-79.0 (62.0±6.9) years. The imaging data and pathological changes before and after neoadjuvant treatment were compared, and adverse reactions during neoadjuvant treatment were recorded. Objective remission rate (ORR) and main pathological remission rate (MPR) and pathological complete remission rate (pCR) were the main observation endpoints. Results After preoperative neoadjuvant therapy with pembrolizumab combined with platinum or paclitaxel, all patients successfully underwent thoracoscopic radical resection of lung cancer. The ORR was 72.7%, and the MPR was 81.8%. Among them, 45.5% of patients achieved pCR. The main adverse reactions were hypoalbuminemia, decreased appetite and nausea. The mortality rate within 30 days after surgery was 0, and no tumor metastasis was observed. Conclusion Pembrolizumab combined with neoadjuvant chemotherapy is safe and feasible to treat non-small cell lung cancer, and the short-term efficacy is beneficial.
5.Development of adolescent health literacy evaluation scale under public health emergencies and its reliability and validity analysis in junior middle school students
Zhou WANG ; Tingye GAO ; Guangjian LI ; Jie ZHOU ; Yaping KONG ; Guihong FAN ; Qian BIAN ; Xing ZHANG ; Shijun ZHAO
Chinese Journal of Behavioral Medicine and Brain Science 2023;32(4):347-354
Objective:To develop and examine the reliability and validity of the adolescent health literacy evaluation scale under public health emergencies (AHLES-PHE) in junior middle school students.Methods:The initial version of AHLES-PHE was formed by combining the characteristics of public health emergencies and adolescent health literacy.The expert version of AHLES-PHE was formed by two rounds of Delphi expert consultation.Totally 1 729 adolescent students from three junior middle schools in Changzhou City were tested.The formal version of AHLES-PHE was formed through item analysis and factor analysis (structural validity). The content validity of the formal version of AHLES-PHE was evaluated by specialist analysis and sensibility analysis, and its correlation validity with the everyday health information literacy (EHIL) was tested.The internal consistency reliability, parity split-half coefficient and test-retest reliability were calculated.Results:(1)Item analysis: the correlation coefficient between the scores of each item and the total score of AHLES-PHE expert version was 0.420 to 0.722 ( P<0.01), and the CR of decision value was 10.140 to 66.980 ( P<0.01). (2)Validity analysis: the formal version of AHLES-PHE with 45 items and 8 factors was obtained by exploratory factor analysis.The 8 factors could explain 61.30% of the total variation.The fitting indexes of the confirmatory factor analysis model were χ2/ df=3.325, RMSEA=0.052, GFI=0.853, CFI=0.912, TLI=0.904, NFI=0.880.Sensibility analysis of the formal version of AHLES-PHE showed the Cronbach's α ranged from 0.957 to 0.958.The correlation coefficient between the total score of AHLES-PHE formal version and the total score of EHIL was 0.340 ( P<0.01). (3)Reliability analysis: the Cronbach's α coefficient and parity split-half coefficient of the formal version of AHLES-PHE were 0.958 and 0.975, respectively.The test-retest reliability of the formal version of AHLES-PHE was 0.753 ( P<0.01). Conclusion:The formal version of AHLES-PHE developed in this study has good reliability, structural validity and content validity, and the correlation validity with EHIL is common.This scale has a certain degree of applicability to the assessment of health literacy for junior middle school students under public health emergencies.
6.Research progress and future directions of adolescent health literacy evaluation tools
Chinese Journal of School Health 2022;43(12):1911-1914
Abstract
Health literacy is closely related to the response to public health emergencies. This paper begins with health literacy evaluation tools in adults, then focuses on recent progress made in health literacy evaluation tools in adolescents from the perspective of public health emergencies. The development of adolescent health literacy evaluation tools, health education and health literacy from the perspective of public health emergencies should be greatly enhanced, helping adolescents to better respond to public health emergencies and maintain their physical and mental health.
7.Thoracic surgery perspective of comprehensive treatment of esophageal cancer with esophagus preserved
Ruiyang SUO ; Zhiyu WANG ; Runyi TAO ; Jinteng FENG ; Kun FAN ; Hongyi WANG ; Heng ZHAO ; Bohao LIU ; Yixing LI ; Yanpeng ZHANG ; Jia ZHANG ; Guangjian ZHANG ; Junke FU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2022;29(02):245-250
Surgery is a classic traditional method for the treatment of early-stage esophageal cancer, and it is also recognized as an effective first-choice method in the medical community. With the development of endoscopic technology, esophagus-preserving comprehensive treatment of esophageal cancer has almost the same or even better effects in some aspects in the treatment of early esophageal cancer than surgery. Many clinical guidelines have also recommended it as the first-choice treatment for early esophageal cancer. The room for surgical treatment of esophageal cancer has been further compressed. This article discusses the comprehensive treatment model of esophageal cancer from the perspective of thoracic surgery, aiming to find a new position of thoracic surgery in the treatment of esophageal cancer.
8.Treatment of Stage Ia Non-small Cell Lung Cancer in Patients: Comparison of Ablation and Sub-lobectomy.
Heng ZHAO ; Kun FAN ; Hongyi WANG ; Bohao LIU ; Yixing LI ; Runyi TAO ; Zhiyu WANG ; Jia ZHANG ; Junke FU ; Guangjian ZHANG
Chinese Journal of Lung Cancer 2021;24(9):613-622
BACKGROUND:
Lung cancer has the highest mortality in China. Different treatments are of great significance to the prognosis of patients. By comparing stage Ia non-small cell lung cancer (NSCLC) patients' survival rates for ablation and for sub-lobectomy, we studied the difference in the effects of the two treatments on patient prognosis.
METHODS:
Using the Surveillance, Epidemiology, and End Results (SEER) database, we screened eligible patients with stage Ia NSCLC from January 2004 to December 2015. Then, 228 patients treated with ablation and 228 patients treated with sub-lobotomy were then selected based on propensity score matching. After stratification, matching, and adjustment the Kaplan-Meier analysis was performed to compare the overall survival rates of patients treated with the two procedures.
RESULTS:
The Kaplan-Meier survival analysis showed that there is a significant difference between the ablation group and the sub-lobectomy group (P<0.05). In the univarlable analysis, the hazard ratio (HR) of sub-lobotomy group was 0.571 (95%CI: 0.455-0.717) compared with the ablation group. Patients treated with sub-lobectomy had a 0.571 times greater risk of adverse outcomes than those treated with ablation. In the multivariable analysis, the HR for sub-lobectomy group was 0.605 (95%CI: 0.477-0.766) compared with the ablation group. Patients treated with sub-lobectomy had a 0.605 time greater risk of adverse outcomes than those treated with ablation. The results suggested that the overall survival rate of patients with stage Ia NSCLC treated with sub-lobotomy was higher than that of patients treated with ablation.
CONCLUSIONS
This study suggests that there is a significant difference in overall survival of stage Ia NSCLC patients treated with ablation and with sub-lobotomy. Patients treated with sub-lobotomy for stage Ia NSCLC had higher overall survival than those treated with ablation.
9.Anatomy of upper lung lobes of patients with small pulmonary nodules based on three-dimensional reconstruction of PC
Kun FAN ; Jinteng FENG ; Hongyi WANG ; Jia ZHANG ; Haiqi HE ; Zhuoqi JIA ; Xiaopeng WEN ; Qifei WU ; Junke FU ; Guangjian ZHANG
Chinese Journal of Thoracic and Cardiovascular Surgery 2020;36(9):557-561
Objective:The extensive development of anatomical pulnonary segmentectomy requires thoracic surgeons to be familiar with the anatomical variations of the lung segment. The purpose of this study is to analyze the anatomical patterns of the right upper lobe lung segment using three-dimensional reconstruction, and to count rare variant types.Methods:From October 2017 to March 2020, 101 patients with small pulmonary nodules who were undergo segmental resection in our center were subjected to preoperative three-dimensional reconstruction of the lung structure, and the reconstruction data was retained for the statistics and analysis of the anatomical structure in the right upper lung lobe.Results:The right upper lobe bronchus is the most common with three branches(77/101), followed by two branches(16/101) and four branches(7/101). The two branches(70/101) of the right upper lobe pulmonary artery are the most common, followed by single branch(19/101) and three branches(11/101). In rare cases, four branches(1/101 cases) can be seen. The two branches(63/101) of the right upper pulmonary vein were the most common, followed by three branches(32/101) and single branch(6/101). In addition, a total of 12 rare mutations were counted. There were 2 variants in the bronchus, totaling 2 cases; 4 rare variants in the pulmonary artery, 13 cases total; 6 rare variants in the pulmonary vein, 10 cases total.Conclusion:The lung anatomy is complex and has many variations. The surgeon should fully grasp the anatomical structure of the lung segment of the patient's operating area before surgery, the data in this article will be a valuable reference for thoracic surgeons to carry out the upper right lobe segmentectomy.
10. Application of panning axial turnover in placement of surgical positions before thoracic surgery
Kun FAN ; Jinteng FENG ; Haiqi HE ; Qifei WU ; Xiaopeng WEN ; Junke FU ; Linjuan ZHANG ; Guangjian ZHANG
Chinese Journal of Practical Nursing 2019;35(13):994-997
Objective:
To evaluate the application of panning axial turnover in placement of surgical positions before thoracic surgery.
Methods:
From June 2017 to September 2017, altogether 140 patients who underwent thoracic surgery were enrolled in and randomly divided into two groups: the observation group and the control group. The control group was treated with traditional turnover method, while the observation group were treated with axial turnover.
Results:
No significant changes were found in blood pressure, heart rate and respiratory rate (


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