1.CeRNA interaction network and immune manifestation of ferroptosis-related signature genes in rheumatoid arthritis
Tian XIA ; Binglin LI ; Fayuan XIAO ; Enze ZHENG ; Yueping CHEN
Chinese Journal of Tissue Engineering Research 2024;28(16):2561-2567
BACKGROUND:Ferroptosis-related genes have been found to play an important role in the pathogenesis of rheumatoid arthritis.However,there is currently a lack of immune expression of ferroptosis-related signature genes in rheumatoid arthritis and the construction of competing endogenous RNA(CeRNA)interaction networks.Machine learning,as a powerful signature gene selection algorithm based on bioinformatics,can more accurately identify ferroptosis-related signature genes that dominate the pathogenesis of rheumatoid arthritis. OBJECTIVE:To screen ferroptosis-related signature genes in rheumatoid arthritis using bioinformatics and machine learning methods,and to analyze the correlation between ferroptosis-related signature genes and immune infiltration and the construction of CeRNA network of ferroptosis-related signature genes. METHODS:Rheumatoid arthritis-related microarrays were obtained from the GEO database,and ferroptosis-related genes and their differential gene expression were extracted using R language.The differentially expressed genes were screened using machine learning methods.The LASSO regression and SVM-RFE methods were used for signature gene screening,and the genes filtered by both were re-intersected to finally obtain the signature genes in rheumatoid arthritis.Receiver operating characteristic curves were used to assess the accuracy of the screened signature genes for disease diagnosis.Immune infiltration of rheumatoid arthritis and normal synovial tissues was analyzed using the CIBERSORT algorithm,and the correlation between the signature genes and immune cells was analyzed.Finally,the CeRNA network of ferroptosis-related signature genes for rheumatoid arthritis was constructed and the disease signature genes were validated. RESULTS AND CONCLUSION:A total of 150 ferroptosis-related genes in rheumatoid arthritis were obtained,including 55 up-regulated genes and 95 down-regulated genes.GO and KEGG enrichment analyses identified 18 GO significantly correlated entries and 30 KEGG entries respectively,mainly involving metal ion homeostasis,ferric ion homeostasis and oxidative stress response.Machine learning analysis finally identified disease signature genes GABARAPL1 and SAT1.GSEA analysis found that adipocytokine signaling pathway,drug metabolism cytochrome P450,fatty acid metabolism,PPAR signaling pathway,tyrosine metabolism were mainly concentrated when GABARAPL1 was highly expressed,and chemokine signaling pathway,intestinal immune network on IGA production were mainly concentrated when SAT1 was highly expressed.Immune infiltration analysis found that nine immune cells were significantly different in rheumatoid arthritis and normal synovial tissues,in which plasma cells,T-cell CD8,and T-cell follicular helper were highly expressed and the rest were lowly expressed in the disease group.Single gene and immune cell correlation analysis found that GABARAPL1 was positively correlated with dendritic resting cells,activated NK cells,and macrophage M1,with the most significant correlation with dendritic resting cells,while SAT1 was positively correlated with T cell CD4 and γδ T cells and negatively correlated with NK resting cells.GSVA analysis found that SAT1 was upregulated in ascorbic acid and aldehyde metabolism,while downregulated in B-cell receptor signaling pathway,Toll-like receptor signaling pathway,T-cell receptor signaling pathway,and natural killer cell-mediated cytotoxicity.GABARAPL1 showed a down-regulation trend in PPAR signaling pathway,metabolism of nicotinate and nicotinamide,tryptophan metabolism,fatty acid metabolism,and steroid biosynthesis.Sixty long non-code RNAs may play a key role in the development of rheumatoid arthritis.To conclude,the occurrence of rheumatoid arthritis is significantly correlated with the abnormal expression of rheumatoid arthritis-induced ferroptosis-related signature genes,and the signature genes induce disease development via relevant signaling pathways.By analyzing rheumatoid arthritis-related long non-code RNAs-mediated ceRNA networks,potential therapeutic targets and signaling pathways can be identified to further elucidate its pathogenesis and provide a reference basis for subsequent experimental studies.
2.Expert consensus on surgical treatment of oropharyngeal cancer
China Anti-Cancer Association Head and Neck Oncology Committee ; China Anti-Cancer Association Holistic Integrative Oral Cancer on Preventing and Screen-ing Committee ; Min RUAN ; Nannan HAN ; Changming AN ; Chao CHEN ; Chuanjun CHEN ; Minjun DONG ; Wei HAN ; Jinsong HOU ; Jun HOU ; Zhiquan HUANG ; Chao LI ; Siyi LI ; Bing LIU ; Fayu LIU ; Xiaozhi LV ; Zheng-Hua LV ; Guoxin REN ; Xiaofeng SHAN ; Zhengjun SHANG ; Shuyang SUN ; Tong JI ; Chuanzheng SUN ; Guowen SUN ; Hao TIAN ; Yuanyin WANG ; Yueping WANG ; Shuxin WEN ; Wei WU ; Jinhai YE ; Di YU ; Chunye ZHANG ; Kai ZHANG ; Ming ZHANG ; Sheng ZHANG ; Jiawei ZHENG ; Xuan ZHOU ; Yu ZHOU ; Guopei ZHU ; Ling ZHU ; Susheng MIAO ; Yue HE ; Jugao FANG ; Chenping ZHANG ; Zhiyuan ZHANG
Journal of Prevention and Treatment for Stomatological Diseases 2024;32(11):821-833
With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth>3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.
3.Long-term efficacy analysis of salvage re-irradiation therapy for patients with locally recurrent esophageal cancer after definitive chemoradiotherapy
Guangbin GAO ; Chen ZHENG ; Qihui LI ; Qing LIU ; Wenpeng JIAO ; Yajing WU ; Yunjie CHENG ; Chang ZHAI ; Yueping LIU ; Jun WANG
Chinese Journal of Radiation Oncology 2024;33(8):711-718
Objective:To analyze clinical features, short-term efficacy and side effects of salvage re-irradiation therapy for patients with locally recurrent esophageal cancer after definitive chemoradiotherapy, to investigate the prognostic factors of re-irradiation with precise radiotherapy techniques.Methods:A retrospective analysis was performed on patients with locally recurrent esophageal squamous cell carcinoma after definitive chemoradiotherapy treated in the Fourth Hospital of Hebei Medical University from January 2008 to December 2016. The patients underwent re-irradiation therapy (re-RT) or re-irradiation therapy concurrent chemotherapy (re-CCRT). The main observation index was after-recurrence survival (ARS), which was calculated by Kaplan-Meier method for survival analysis. Univariate analysis was conducted by log-rank test, and multivariate analysis was performed by Cox regression model.Results:A total of 109 patients were included, with a median age of 66 years (43-89 years), and a median follow-up time of 120.8 months (79.0-176.5 months). The objective response rates (ORR) and dysphagia improvement rates (DIR) in all patients were 64.2% and 63.0%, respectively. The median ARS and 1-, 3-, 5-, 8-year survival rates in all patients were 7.8 months and 32.1%, 9.2%, 7.3% and 2.3%, respectively. The median ARS and 1-, 3-, 5-years survival rates were 10.8 months and 45.9%, 13.5%, 10.8% for patients with time to recurrence (TTR) ≥24 months, significantly longer than those of 5.7 months and 25.0%, 6.9%, 5.6% for patients with TTR<24 months ( χ2=7.99, P=0.005). The median ARS in groups with re-irradiation dose of ≤50 Gy,>50-54 Gy, and>54 Gy groups were 5.7, 10.0 and 8.1 months, respectively ( χ2=6.94, P=0.031). The 1-, 3- and 5-year survival rates were 30.4%, 5.1%, and 3.8% for re-RT versus 36.7%, 20.0%, and 16.7% for re-CCRT ( χ2=2.12, P=0.145). Multivariate analysis showed that TTR ( HR=0.607, 95% CI=0.372-0.991, P=0.046) and lesion length ( HR=0.603, 95% CI=0.371-0.982, P=0.042) were the independent factors for ARS. There was no significant difference in ≥2 grade pneumonitis and 2-3 grade radiation esophagitis between the re-RT and re-CCRT groups ( χ2=0.25, P=0.619; χ2=0.51, P=0.808). The morbidity of ≥2 grade myelosuppression in the re-RT group was significantly lower than that in the re-CCRT group (3.7% vs. 36.7%, χ2=18.15, P<0.001). Conclusions:Precise re-irradiation therapy for patients with locally recurrent esophageal cancer after definitive chemoradiotherapy can alleviate dysphagia, but ARS remains poor. Re-irradiation dose range from>50-54 Gy may be suitable for locally relapse patients as salvage treatment. Patients with TTR≥24 months and lesion length ≤5 cm obtain favorable prognosis.
4.Analysis of predictive effect of European treatment and outcome study long term survival score on survival outcomes in children with chronic myeloid leukemia of chronic phase
Fangyuan ZHENG ; Ruizhe DENG ; Aidong LU ; Yueping JIA ; Huimin ZENG ; Leping ZHANG ; Qian JIANG
Chinese Journal of Pediatrics 2024;62(10):956-961
Objective:To explore the predictive effect of European treatment and outcome study long term survival (ELTS) score on survival outcomes in chronic myeloid leukemia of chronic phase (CML-CP) children.Methods:A single-center retrospective cohort study was conducted. Clinical data of 216 children with CML-CP in Peking University People′s Hospital from January 2010 to December 2023 were analyzed. Children were divided into low, intermediate and high-risk groups according to ELTS score. The survival outcomes and prognostic factors were analyzed. Kaplan-Meier method and Log-Rank test were used for survival analysis.Cox regression model was applied for analysis of prognostic factors.Results:Among the 216 children with CML-CP, there were 122 males and 94 females, with the diagnosis age of 11.0 (8.0, 14.7) years. The follow-up time was 77 (57, 99) months. According to ELTS score, 145, 52, and 19 children were classified as low, intermediate and high-risk group. For the low-risk and intermediate/high-risk groups, the 6-year failure-free survival (FFS) rates were (83.0±3.1)% and (64.6±5.7)%, the 6-year progression-free survival (PFS) rates were (91.4±2.3)% and (78.7±4.8)%, and the 6-year event-free survival (EFS) rates were (80.8±3.3)% and (64.2±5.7)%, with statistically significant difference ( χ2=9.45, 7.16, 7.40, P=0.002, 0.007, 0.007), respectively.The 6-year overall survival (OS) rates were (98.5±1.0)% and (95.6±2.4)%, without statistically significant difference ( χ2=0.35, P=0.550). Multivariate analysis showed that ELTS score was an independent prognostic factor or tendency for FFS ( HR=1.97, 95% CI 1.11-3.49), PFS ( HR=2.95, 95% CI 1.18-7.39), and no independent prognostic factor for EFS and OS were found. Conclusions:ELTS score at diagnosis can help stratify the risk of children with CML-CP. The children in intermediate/high-risk group are more likely to have treatment failure, disease progression than those in low-risk group, but the predictive ability of ELTS score for OS is limited.
5.Research on the clinical characteristics and prognosis of children with chronic myeloid leukemia in the blast phase
Fangyuan ZHENG ; Aidong LU ; Yueping JIA ; Yingxi ZUO ; Huimin ZENG ; Qian JIANG ; Leping ZHANG
Chinese Journal of Hematology 2024;45(10):931-936
Objective:To explore the clinical characteristics and prognosis of children with chronic myeloid leukemia in the blast phase (CML-BP) .Methods:The clinical characteristics, treatment measures, and survival outcomes of 28 children with CML-BP were analyzed in our hospital from January 2008 to November 2022.Results:The male to female ratio of the 28 children with CML-BP was 1.15∶1. The median age of diagnosis of CML-BP was 10 years, and the median follow-up time was 79 months. During the diagnosis of CML, four children were in the BP, one was in the accelerated phase (AP) and 23 children were in the chronic phase (CP). Among the 23 children with CML-CP, 75% had progressed directly from CP to BP without experiencing the AP. Among the children diagnosed with CML-BP, 71.4% were classified as chronic myeloid leukemia lymphoid blast phase (CML-LBP), 25.0% belonged to the chronic myeloid leukemia myeloid blast phase (CML-MBP), and 3.6% belonged to the chronic myeloid leukemia mixed phenotype acute leukemia (CML-MPAL). Treatment with hemaopoietic stem cell transplantation (HSCT) after tyosine kinase inhibitor (TKI) combined with chemotherapy was administered to 19 children, two children received HSCT after TKI alone, and seven children received TKI combined with chemotherapy but without HSCT. The 5-year overall survival of the 28 children with CML-BP was 59.3%.Conclusion:The direct progression of BP from CP is greater in children with CML-BP compared with adults, and the overall prognosis of children with CML-BP is poor.
6.Comparative Study on Different Serology Risk Stratification Combined With Endoscopy for Screening of Early Gastric Cancer
Yueping ZHENG ; Ping JIANG ; Zhi NI ; Rongchun ZHANG
Chinese Journal of Gastroenterology 2023;28(11):672-676
Background:One effective method for detecting stomach cancer is serological screening.Aims:To improve the prognosis and better direct clinical practice,this research compares the usefulness of the new scoring system and the ABC method in the screening of high-risk lesions of gastric cancer.Methods:This study involved the consecutive enrollment of 2 306 individuals(of whom 1 232 were male and 1 074 were female)who had gastroscopy at the Physical Examination Department of Xiamen Humanity Hospital between December 2020 and December 2022 and were above the age of 40.Before endoscopy,the population was classified as low-risk,intermediate-risk,and high-risk based on the serological ABC method and the new scoring system,respectively,and based on the age,gender,serum Helicobacter pylori antibody,PGR,and G-17 test findings of the studied population.An analysis was conducted on the identification of high-risk lesions of stomach cancer using the two distinct approaches,and the usefulness of the two distinct techniques for identifying high-risk lesions associated with stomach cancer was assessed.Results:Based on the serological ABC method of 2 306 patients,there were 1 293 cases in the low-risk group,856 cases in the intermediate-risk group,and 157 cases in the high-risk group.Of the three groups,759 cases(58.7%)had high-risk lesions of gastric cancer,492 cases(57.5%)in the intermediate-risk group,and 82 cases(52.2%)in the high-risk group.There were 1 899 cases in the low-risk category,383 cases in the intermediate-risk group,and 27 cases in the high-risk group,based on the novel scoring system.Among them,1 044 patients had high-risk stomach cancer lesions found.There were 18 instances(75.0%)in the high-risk group and 271 cases(70.8%)in the intermediate-risk group.The identification rate of high-risk lesions of gastric cancer in the new scoring method increases progressively as the group grade rises(χ2=35.482,P<0.001).Conclusions:While both approaches are useful for identifying high-risk gastric cancer lesions,the novel scoring system may be more beneficial for identifying these lesions early on.
7.Construction of post competency model of human organ donation coordinators based on onion model
Jianquan WU ; Manman SHANG ; Guifang ZHENG ; Qin WEI ; Xianyu XIE ; Yueping LI
Organ Transplantation 2023;14(5):714-722
Objective To construct a scientific and rational post competency model of human organ donation coordinators. Methods Based on the onion model, the index pool was initially constructed by literature research and behavioral event interview. The index system was screened, modified and improved using Delphi method. The weight of indexes at all levels was determined by analytic hierarchy process. Results The effective response rates of two rounds of Delphi expert inquiries were both 100%, indicating that the expert opinions were highly dependable. The experts' judgment coefficient (Ca), familiarity (Cs) and authoritative coefficient (Cr) were all above 0.7, indicating that the experts' opinions were highly reliable. The expert coordination coefficients (W) were 0.294 and 0.342 (both P<0.001), indicating that experts delivered coordinated opinions and yielded slight difference in understanding the importance of indexes. Finally, according to the "onion model" theory and experts' opinions, a set of coordinator's post competency model including 6 first-level and 55 second-level indexes was established, which comprised an index surface layer, a middle layer and a core layer. Among them, the core layer represented core professional values, the middle layer was personal quality and professional ethics and quality, and the surface layer was interpersonal communication capability, organizational cooperation capability and professional knowledge and lifelong learning capability. Conclusions The post competency model of organ donation coordinators established in this study consists of 6 first-level and 55 second-level indexes, which is highly effective and reliable.
8.Analysis on the Difficulties and Strategies in Promoting the Red Doctor’s Culture: Taking Western Fujian as an Example
Chinese Medical Ethics 2023;36(7):799-803
Red doctor’s culture is a precious spiritual wealth formed in the medical and health practice of the Central Soviet Area during a specific historical period. With the development of society and the changes of the times, the red doctor’s culture has been endowed with new connotation. Western Fujian was the earliest place to provide medical support for the revolutionary army, the birthplace of the Republic’s health service, and made great contributions to the victory of the Chinese revolution. The cultural resources of red doctor’s in western Fujian are abundant, and it is one of the important lineages of the red culture in western Fujian, with its unique historical value. At present, there are many problems in promoting the red doctor’s culture. Actively exploring and researching specific paths and methods to promote the red doctor’s culture is of great significance and value for giving full play to the connotation of the red doctor’s culture in the new era, promoting its value leading role at various levels of society, and passing down the spirit and culture of red doctor’s.
9.Improved outcomes in E2A::HLF positive B-cell acute lymphoblastic leukemia by chimeric antigen receptor T cell therapy and BCL-2 inhibitor.
Shumin CHEN ; Ye LI ; Zheng WANG ; Lin FENG ; Yueping JIA ; Xiaodong MO ; Yu WANG ; Qian JIANG ; Xiaojun HUANG ; Yueyun LAI
Chinese Medical Journal 2023;136(11):1382-1384
10.Establishment and validation of a multigene model to predict the risk of relapse in hormone receptor-positive early-stage Chinese breast cancer patients.
Jiaxiang LIU ; Shuangtao ZHAO ; Chenxuan YANG ; Li MA ; Qixi WU ; Xiangzhi MENG ; Bo ZHENG ; Changyuan GUO ; Kexin FENG ; Qingyao SHANG ; Jiaqi LIU ; Jie WANG ; Jingbo ZHANG ; Guangyu SHAN ; Bing XU ; Yueping LIU ; Jianming YING ; Xin WANG ; Xiang WANG
Chinese Medical Journal 2023;136(2):184-193
BACKGROUND:
Breast cancer patients who are positive for hormone receptor typically exhibit a favorable prognosis. It is controversial whether chemotherapy is necessary for them after surgery. Our study aimed to establish a multigene model to predict the relapse of hormone receptor-positive early-stage Chinese breast cancer after surgery and direct individualized application of chemotherapy in breast cancer patients after surgery.
METHODS:
In this study, differentially expressed genes (DEGs) were identified between relapse and nonrelapse breast cancer groups based on RNA sequencing. Gene set enrichment analysis (GSEA) was performed to identify potential relapse-relevant pathways. CIBERSORT and Microenvironment Cell Populations-counter algorithms were used to analyze immune infiltration. The least absolute shrinkage and selection operator (LASSO) regression, log-rank tests, and multiple Cox regression were performed to identify prognostic signatures. A predictive model was developed and validated based on Kaplan-Meier analysis, receiver operating characteristic curve (ROC).
RESULTS:
A total of 234 out of 487 patients were enrolled in this study, and 1588 DEGs were identified between the relapse and nonrelapse groups. GSEA results showed that immune-related pathways were enriched in the nonrelapse group, whereas cell cycle- and metabolism-relevant pathways were enriched in the relapse group. A predictive model was developed using three genes ( CKMT1B , SMR3B , and OR11M1P ) generated from the LASSO regression. The model stratified breast cancer patients into high- and low-risk subgroups with significantly different prognostic statuses, and our model was independent of other clinical factors. Time-dependent ROC showed high predictive performance of the model.
CONCLUSIONS
A multigene model was established from RNA-sequencing data to direct risk classification and predict relapse of hormone receptor-positive breast cancer in Chinese patients. Utilization of the model could provide individualized evaluation of chemotherapy after surgery for breast cancer patients.
Humans
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Female
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Breast Neoplasms/genetics*
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East Asian People
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Neoplasm Recurrence, Local/genetics*
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Breast
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Algorithms
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Chronic Disease
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Prognosis
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Tumor Microenvironment


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