1.Research Tackling Paradigm and Technological Layout Strategies Based on Erectile Dysfunction, A Clinical Dominant Disease of Traditional Chinese Medicine
Qi ZHAO ; Yun CHEN ; Baoxing LIU ; Xuejun SHANG ; Fei SUN ; Xiaozhi ZHAO ; Zhigang WU ; Chao SUN ; Peihai ZHANG ; Wanjun CHENG ; Xing ZHOU ; Zhan QIN ; Yufeng PAN ; Weiwei TAO ; Jianhuai CHEN ; Mei MO ; Xiaoxiao ZHANG ; Xing ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):291-299
To thoroughly implement the strategic deployment outlined in the Opinions of the Central Committee of the Communist Party of China and the State Council on Promoting the Inheritance and Innovative Development of Traditional Chinese Medicine regarding research on dominant diseases of traditional Chinese medicine and to uphold the development philosophy of equal emphasis on traditional Chinese medicine and western medicine,the China Association of Chinese Medicine has fully played a leading academic role by systematically organizing and conducting a series of academic youth salons on clinical dominant diseases of traditional Chinese medicine. On September 13,2024,the 36th Youth Salon on Clinical Dominant Diseases was successfully held in Nanjing,focusing on the advantages of traditional Chinese medicine and the integrative traditional Chinese medicine and western medicine in the diagnosis and treatment of erectile dysfunction (ED). The conference brought together leading experts from traditional Chinese medicine,western medicine,and interdisciplinary fields,facilitating in-depth multidisciplinary discussions that led to key consensus on optimizing traditional Chinese medicine treatment protocols for ED,researching and developing new drugs of traditional Chinese medicine,and advancing interdisciplinary development in traditional Chinese medicine. This salon systematically sorted out the clinical strengths and distinctive features of traditional Chinese medicine in the diagnosis and treatment of ED. Based on current research foundations and clinical needs,it identified key directions for future scientific layout and scientific research tackling: (1) Standardization of syndrome differentiation system of traditional Chinese medicine for ED. (2) Optimization and standardization of intervention methods of integrated traditional Chinese medicine and western medicine. (3) High-quality clinical research guided by evidence-based medicine. (4) In-depth analysis of the pharmacological mechanisms of traditional Chinese medicine in the treatment of ED. (5) Clinical translation and application promotion of new drugs of traditional Chinese medicine. (6) Interdisciplinary integration and innovation in traditional Chinese medicine. For each research direction,key focus areas,expected objectives,and clinical value were further refined,along with the establishment of a scientifically sound priority funding level evaluation system. Therefore,building on the series of salons on the ED-focused dominant diseases of traditional Chinese medicine,this paper provides standardized guidance for clinical practice of traditional Chinese medicine in ED management,effectively contributing to the high-quality development of traditional Chinese medicine. It serves as a valuable reference for national scientific and technological strategic layout, research and development decision-making in new drugs of traditional Chinese medicine,research topic planning,and clinical guideline formulation.
2.Construction and Practice of AI-Based Triadic Interactive Teaching Model for Surgical Animal Surgery
Kaikai MAO ; Xiu LI ; Chen ZHOU ; Jianfeng SANG ; Meng WANG ; Guang ZHANG ; Xiaozhi ZHAO
Laboratory Animal and Comparative Medicine 2026;46(2):288-296
ObjectiveIn the context of the digital transformation of education, this study aims to construct a triadic interactive teaching model for surgical animal surgery in clinical medicine using modern information technology. It explores the effectiveness of different teaching methods in improving students' practical skills, aseptic awareness, and teamwork abilities, providing a reference for the reform of clinical practice education. MethodsA quasi-experimental research design was adopted. A total of 80 students from the eight-year clinical medicine program at Nanjing University were selected, including the Class of 2020 (control group, n=40) and the Class of 2021 (experimental group, n=40). The control group received traditional teaching methods, while the experimental group implemented the "Teacher-Student-AI" triadic interactive teaching model. This model utilized a smart teaching platform for personalized pre-class preparation , as well as data-driven post-class review and feedback throughout the entire teaching process. The "assessment indicators and scoring criteria for the surgical animal surgery course" were used to evaluate teaching effectiveness, with independent samples t-tests used for statistical analysis. ResultsPre-course assessments revealed no statistically significant differences in baseline theoretical knowledge or practical skills between the two groups (P>0.05). Upon completion of the course, the experimental group achieved higher scores than the control group across three key dimensions: practical skills (47.98±1.34 vs 46.92±2.51, P=0.022), aseptic awareness (17.84±1.16 vs 16.94±2.29, P=0.029), and teamwork (16.82±1.44 vs 15.95±1.22, P=0.004). However, no statistically significant difference was observed in the scores for humane care awareness between the two groups (8.24±0.70 vs 8.16±0.53, P=0.589). ConclusionThe AI-based triadic interactive teaching model can, to some extent, address the limitations of traditional surgical animal surgery education. It plays a positive role in enhancing medical students' surgical skills, aseptic awareness, and collaborative abilities. This model facilitates the transition from traditional to personalized teaching and offers a practical framework for the digital reform of clinical practice education.
3.Expert consensus on neoadjuvant PD-1 inhibitors for locally advanced oral squamous cell carcinoma (2026)
LI Jinsong ; LIAO Guiqing ; LI Longjiang ; ZHANG Chenping ; SHANG Chenping ; ZHANG Jie ; ZHONG Laiping ; LIU Bing ; CHEN Gang ; WEI Jianhua ; JI Tong ; LI Chunjie ; LIN Lisong ; REN Guoxin ; LI Yi ; SHANG Wei ; HAN Bing ; JIANG Canhua ; ZHANG Sheng ; SONG Ming ; LIU Xuekui ; WANG Anxun ; LIU Shuguang ; CHEN Zhanhong ; WANG Youyuan ; LIN Zhaoyu ; LI Haigang ; DUAN Xiaohui ; YE Ling ; ZHENG Jun ; WANG Jun ; LV Xiaozhi ; ZHU Lijun ; CAO Haotian
Journal of Prevention and Treatment for Stomatological Diseases 2026;34(2):105-118
Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.
4.Construction and verification of a prognostic model combining anoikis and immune prognostic signatures for primary liver cancer.
Ying WANG ; Jing LI ; Yidi WANG ; Mingyu HUA ; Weibin HU ; Xiaozhi ZHANG
Journal of Southern Medical University 2025;45(9):1967-1979
OBJECTIVES:
To establish a prognostic model for primary liver cancer (PLC) using bioinformatics methods.
METHODS:
Based on the data from 404 patients in the Cancer Genome Atlas (TCGA) database, we constructed a prognostic model integrating the differentially expressed genes, anoikis, and immune-related genes (DAIs) using univariate Cox regression and the LASSO-Cox approach. The predictive ability of the model was evaluated using Kaplan-Meier method and receiver-operating characteristic curves, and a nomogram was developed to facilitate its clinical applications. Gene set enrichment analysis (GSEA) was performed to explore the associated pathways and relationship between the DAIs and the tumor immune microenvironment, and the half-maximal inhibitory concentration (IC50) of liver cancer drugs was calculated using the "pRRophetic" R package. We also detected the expression of SEMA7A in paired tumor and adjacent tissues from liver cancer patients.
RESULTS:
We constructed and validated a prognostic model based on 7 DAIs (NR4A3, SEMA7A, IL11, AR, BIRC5, EGF, and SPP1), and obtained consistent results in both the TCGA training cohort and GEO validation cohort (GSE14520), where the patients in the low-risk group were characterized by more favorable clinical outcomes and immune status. By integrating this prognostic signature with clinical information, a composite nomogram was generated. Somatic mutation analysis showed that TTN, TP53, and CTNNB1 mutations accounted for the largest proportion of total mutations, and the patients in the low-risk-low-TMB group had higher survival rate. Drug sensitivity analysis revealed differences in sensitivity to chemotherapeutic agents between high- and low-risk groups and between TP53 mutations and non-mutations. In clinical tissue specimens, SEMA7A expression was significantly higher in liver cancer tissues than in the adjacent tissues.
CONCLUSIONS
We established a new prognostic model based on DAIs for predicting clinical outcomes and therapeutic response of patients with primary liver cancer.
Humans
;
Liver Neoplasms/diagnosis*
;
Prognosis
;
Anoikis
;
Nomograms
;
Computational Biology
;
Tumor Microenvironment
;
Semaphorins/metabolism*
5.Indoleamine-2,3-dioxygenase 1 mediated enhanced tryptophan metabolism affects radiation resistance in esophageal squamous cell carcinoma
Chao JI ; Weibin HU ; Ying WANG ; Fengyi QU ; Yuchen XIE ; Siqi LIU ; Xiaozhi ZHANG ; Yuchen SUN
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(1):78-85
Objective To explore the biological mechanism of radiation resistance in esophageal squamous cell carcinoma(ESCC)and search for effective sensitization targets.Methods We retrieved 186 signaling pathways and related gene information from the MSigDB database.We also obtained RNA transcriptome data of ESCC patients using the Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.We collected clinical pathological characteristics and tissue samples of 97 ESCC patients in our hospital from 2013 to 2020.Gene set variation analysis(GSVA)was made to calculate KEGG signaling pathway score,radiotherapy resistance related signaling pathways were screened through random forest algorithm,key genes in the pathway were screened using DESeq2,and a radiotherapy efficacy prediction model was constructed based on support vector machine-recursive feature elimination(SVM-RFE).The results were validated through experiments such as Western blotting and clonogenic assay.Results Based on the KEGG signaling pathway and GSVA enrichment score,random forest analysis showed that in the TCGA and GSE45670 cohorts,the contribution of tryptophan metabolism pathway enrichment values to radiation resistance in ESCC was significantly better than that of the other pathways.DESeq2 analysis revealed that key molecules in the tryptophan metabolism pathway,namely,IDO1,ALDH1B1,AOC1,INMT,AFMID and ALDH7A1,were significantly differentially expressed in the resistant and sensitive groups of ESCC.Based on the SVM-RFE algorithm,the AUC was 0.77,which could accurately predict the radiotherapy efficacy of ESCC.Western blotting experiments showed that IDO1 was highly expressed in ESCC cells,and IDO1 inhibitor treatment significantly inhibited the survival ability and radiosensitivity of KYSE-410 cells.In the enrolled patients of our hospital,immunohistochemical studies showed that IDO1 was highly expressed in the radiotherapy resistant group of ESCC and was associated with poor radiotherapy prognosis in ESCC patients.In addition,further testing showed that the expression of IDO1 in patient samples from our hospital was positively correlated with its PD-L1 expression,but negatively correlated with the infiltration ratio of CD3/CD8 immune cells.Conclusion Tryptophan catabolism is associated with radiation resistance in ESCC,and the key enzyme IDO1 in tryptophan metabolism can be used as a therapeutic target for radiosensitization in ESCC.
6.Construction and validation of an osteoporosis risk prediction model for middle-aged and elderly healthy physical examination population
Dongqing HUANG ; Wei LI ; Xiaozhen LI ; Liping CHEN ; Zhang′an WANG ; Jia TAN ; Xiaozhi HUANG ; Yinghua LUO
Chinese Journal of Health Management 2025;19(5):355-361
Objective:To construct and validate the risk prediction model of osteoporosis (OP) in the middle-aged and elderly healthy physical examination population.Methods:In this cross-sectional study, 18 030 middle-aged and elderly people with bone mineral density tested in Health Management Center of Guangxi Zhuang Autonomous Region Hospital from January 2020 to December 2022 were selected. The general data, physical examination index and biochemical blood index were collected. The subjects were divided into training set (12 621 cases) and validation set (5 409 cases) in a ratio of 7∶3 with the simple random sampling method. The variables were screened with minimum LASSO regression and logistic regression and the corresponding nomogram prediction model for the risk of osteoporosis in the middle-aged and elderly health examination population was established. The performance of the nomogram model was evaluated with the area under the receiver operating characteristic curve (ROC AUC), specificity, sensitivity, calibration curve (CAL), and decision curve (DCA).Results:The results of LASSO regression and multivariate logistic regression in training set showed that gender, age, body mass index, hip circumference, waist circumference, systolic blood pressure, total cholesterol, glutamyl transpeptidase and albumin/globulin ratio were the independent best predictors of OP risk in the middle-aged and elderly health examination population (all P<0.05). The ROC AUC-value of the training set was 0.895 (95% CI: 0.886-0.904), with a sensitivity of 87.25% and a specificity of 85.01%. The ROC AUC value of the validation set was 0.892 (95% CI: 0.886-0.898), with a sensitivity of 83.74% and a specificity of 82.46%. The CAL showed a C-index value of 0.790 in the training set and a C-index value of 0.784 in validation set. The CALs all showed deviation correction and obvious curves similar to the ideal line. DCA showed that when the OP risk threshold probability of the training set was 45%-93%, and the OP risk threshold probability of the validation set was 45%-92%, the nomogram model had better efficacy in predicting OP risk in the middle-aged and elderly physical examination population, and the two results were still relatively consistent. Both CAL and DCA showed good performance. Conclusion:This study establishes a practical prediction model for osteoporosis risk in the middle-aged and elderly population, it can provide an early warning for the timely detection of OP risk for the middle-aged and elderly people.
7.Effect of Prophyromonas gingivalis on the Occurrence of PND in Mice via TLR4/NF-κB Signaling Pathway
Xiaojuan XIE ; Shuang ZHANG ; Xiaozhi BAI
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong 2025;54(4):483-490
Objective To investigate whether Porphyromonas gingivalis(Pg)in the oral cavity can influence the occurrence of perioperative neurocognitive disorder(PND)by modulating the TLR4/NF-κB signaling pathway.Methods In cell experi-ment,BV-2 cells in the logarithmic growth phase were randomly divided into two groups:the control group(Group C)and the LPS-Pg-treatedgroup(Group P).Western blot was used to detect the expression levels of signaling proteins(TLR4,NF-κB p65,NLRP3,TNF-α)in cellular proteins.Immunofluorescence assay was employed to observe thechanges in NF-κB p65 expres-sions inside and outside the nucleus.In animal experiments,C57BL/6 mice were randomly divided into six groups:the control group(Group C),the surgery group(Group S),the Pg infection group(Group P),the Pg infection+surgery group(Group PS),the TLR4inhibitor group(Group T),and the Pg infection+surgery+TLR4 inhibitor group(Group PST).After corresponding treatments,the Morris water maze(MWM)test was applied to observe theeffects of Pg infection on postoperativecognitive be-havior in mice.Immunohistochemical analysis was used to assess the impact of Pg infection on the activation of microglia in the hippocampal tissue of mice.Results In cell experiment,compared with Group C,expression levels of TLR4,NLRP3,and TNF-α increased significantly in Group P(all P<0.05).The expression of NF-κB p65 in the nucleus increased(P<0.05),while its expression outside the nucleus decreased(P<0.05).Immunofluorescence results showed increased NF-κB expression and its translocation into the nucleus in Group P.As for animal experiment,no significant difference was observed in the preoperative training phase among the groups in Morris water maze experiment,with similar escape latencies and average swimming speeds(all P>0.05).Therefore,therewas no notabledifferences in navigationand swimming abilities among thegroups before theex-periment.In the postoperative testing phase,compared with Group C,the target quadrant time and platform-crossing times were less in mice of Group S and Group PS(all P<0.05).Compared with Group PS,the target quadrant time and platform-crossing times were elevated in mice of Group PST(both P<0.05).Compared to Group C and Group PST,number of positive cells in hippocampal tissue was higher in Group PS.These positivecells exhibited enlarged somas,shortened processes,and an activated state of microglia.Conclusion Pg infection induces enhanced central nervous system inflammation during the perioperative peri-od in mice,leading to the occurrence of PND,possibly through the activation of the TLR4/NF-κB signaling pathway.
8.Effects of Remimazolam combined with Esketamine on cellular immunity,cognitive function,and sleep quality in elderly patients with lung cancer
Yanhui HE ; Xiaozhi BAI ; Yongjie ZHANG ; Jin LIU ; Xiao SHANG
Immunological Journal 2025;41(10):726-733,742
Objective To investigate the effects of Remimazolam combined with Esketamine on cellular immunity,cognitive function,and sleep quality in elderly patients with lung cancer during surgery.Methods A total of 106 elderly lung cancer patients who underwent elective thoracoscopic lobectomy from September 2023 to March 2025 were selected and divided into the control group(n=53)and the research group(n=53)according to random number table method.The control group received Midazolam combined with Esketamine for general anesthesia,while the research group received Remimazolam combined with Esketamine for general anesthesia.The intraoperative and postoperative conditions,hemodynamic parameters[heart rate(HR),mean arterial pressure(MAP)]before anesthesia induction(T0),at tracheal intubation(T1),at 1 min before one-lung ventilation(OLV)(T2),at skin incision(T3),at 1 h after OLV(T4),and immediately after extubation(T5),as well as pain and inflammatory factors[5-hydroxytryptamine(5-HT),prostaglandin E2(PGE2),high-sensitivity C-reactive protein(hs-CRP),tumor necrosis factor-α(TNF-α)],cellular immunity[peripheral blood natural killer(NK)cells,CD3+,CD4+,CD4+/CD8+],the levels of serum interleukin(IL)-2,interferon-γ(IFN-γ),cognitive function[Mini-Mental State Examination(MMSE)],sleep quality[Pittsburgh Sleep Quality Index(PSQI)],and recovery quality[Postoperative Quality of Recovery-15(QoR-15)score]were compared between the two groups of patients.The adverse reactions and complications were also compared between the two groups.Results There was no significant difference in duration of surgery,duration of anesthesia,intraoperative blood loss,and time to spontaneous breathing recovery of patients between the two groups(P>0.05).The total dosage of Sufentanil in the research group was less than that in the control group,and time to postoperative eye opening,duration of recovery room stay and length of postoperative hospitalization were shorter than those in the control group(P<0.05).At T0 and T5,there was no significant difference in HR and MAP between the two groups(P>0.05),and at T1-T4,HR and MAP in the research group were higher than those in the control group(P<0.05).At the time of recovery,the levels of serum 5-HT,PGE2,hs-CRP,and TNF-α in the research group were lower than those in the control group(P<0.05),and at the time of recovery,the peripheral blood NK cells,CD3+,CD4+,and CD4+/CD8+ratio,serum IL-2 and IFN-γ levels in the research group were higher than those in the control group(P<0.05).At 1 d after surgery,the MMSE and QoR-15 scores of the research group were higher than those of the control group,while the PSQI score was lower than that of the control group(P<0.05).The incidence of adverse reactions and complications in the research group[5.66%(3/53)and 3.77%(2/53)],was lower than that of the control group[18.87%(10/53)and 15.09%(8/53)](P<0.05).Conclusion The combination of Remimazolam and Esketamine in elderly patients undergoing thoracoscopic lobectomy can better maintain intraoperative hemodynamics,stabilize cellular immune function,reduce serum pain and inflammatory factor levels,improve postoperative cognitive function and sleep quality,reduce adverse reactions and complications,and promote postoperative recovery.
9.Effect of Prophyromonas gingivalis on the Occurrence of PND in Mice via TLR4/NF-κB Signaling Pathway
Xiaojuan XIE ; Shuang ZHANG ; Xiaozhi BAI
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong 2025;54(4):483-490
Objective To investigate whether Porphyromonas gingivalis(Pg)in the oral cavity can influence the occurrence of perioperative neurocognitive disorder(PND)by modulating the TLR4/NF-κB signaling pathway.Methods In cell experi-ment,BV-2 cells in the logarithmic growth phase were randomly divided into two groups:the control group(Group C)and the LPS-Pg-treatedgroup(Group P).Western blot was used to detect the expression levels of signaling proteins(TLR4,NF-κB p65,NLRP3,TNF-α)in cellular proteins.Immunofluorescence assay was employed to observe thechanges in NF-κB p65 expres-sions inside and outside the nucleus.In animal experiments,C57BL/6 mice were randomly divided into six groups:the control group(Group C),the surgery group(Group S),the Pg infection group(Group P),the Pg infection+surgery group(Group PS),the TLR4inhibitor group(Group T),and the Pg infection+surgery+TLR4 inhibitor group(Group PST).After corresponding treatments,the Morris water maze(MWM)test was applied to observe theeffects of Pg infection on postoperativecognitive be-havior in mice.Immunohistochemical analysis was used to assess the impact of Pg infection on the activation of microglia in the hippocampal tissue of mice.Results In cell experiment,compared with Group C,expression levels of TLR4,NLRP3,and TNF-α increased significantly in Group P(all P<0.05).The expression of NF-κB p65 in the nucleus increased(P<0.05),while its expression outside the nucleus decreased(P<0.05).Immunofluorescence results showed increased NF-κB expression and its translocation into the nucleus in Group P.As for animal experiment,no significant difference was observed in the preoperative training phase among the groups in Morris water maze experiment,with similar escape latencies and average swimming speeds(all P>0.05).Therefore,therewas no notabledifferences in navigationand swimming abilities among thegroups before theex-periment.In the postoperative testing phase,compared with Group C,the target quadrant time and platform-crossing times were less in mice of Group S and Group PS(all P<0.05).Compared with Group PS,the target quadrant time and platform-crossing times were elevated in mice of Group PST(both P<0.05).Compared to Group C and Group PST,number of positive cells in hippocampal tissue was higher in Group PS.These positivecells exhibited enlarged somas,shortened processes,and an activated state of microglia.Conclusion Pg infection induces enhanced central nervous system inflammation during the perioperative peri-od in mice,leading to the occurrence of PND,possibly through the activation of the TLR4/NF-κB signaling pathway.
10.Indoleamine-2,3-dioxygenase 1 mediated enhanced tryptophan metabolism affects radiation resistance in esophageal squamous cell carcinoma
Chao JI ; Weibin HU ; Ying WANG ; Fengyi QU ; Yuchen XIE ; Siqi LIU ; Xiaozhi ZHANG ; Yuchen SUN
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(1):78-85
Objective To explore the biological mechanism of radiation resistance in esophageal squamous cell carcinoma(ESCC)and search for effective sensitization targets.Methods We retrieved 186 signaling pathways and related gene information from the MSigDB database.We also obtained RNA transcriptome data of ESCC patients using the Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.We collected clinical pathological characteristics and tissue samples of 97 ESCC patients in our hospital from 2013 to 2020.Gene set variation analysis(GSVA)was made to calculate KEGG signaling pathway score,radiotherapy resistance related signaling pathways were screened through random forest algorithm,key genes in the pathway were screened using DESeq2,and a radiotherapy efficacy prediction model was constructed based on support vector machine-recursive feature elimination(SVM-RFE).The results were validated through experiments such as Western blotting and clonogenic assay.Results Based on the KEGG signaling pathway and GSVA enrichment score,random forest analysis showed that in the TCGA and GSE45670 cohorts,the contribution of tryptophan metabolism pathway enrichment values to radiation resistance in ESCC was significantly better than that of the other pathways.DESeq2 analysis revealed that key molecules in the tryptophan metabolism pathway,namely,IDO1,ALDH1B1,AOC1,INMT,AFMID and ALDH7A1,were significantly differentially expressed in the resistant and sensitive groups of ESCC.Based on the SVM-RFE algorithm,the AUC was 0.77,which could accurately predict the radiotherapy efficacy of ESCC.Western blotting experiments showed that IDO1 was highly expressed in ESCC cells,and IDO1 inhibitor treatment significantly inhibited the survival ability and radiosensitivity of KYSE-410 cells.In the enrolled patients of our hospital,immunohistochemical studies showed that IDO1 was highly expressed in the radiotherapy resistant group of ESCC and was associated with poor radiotherapy prognosis in ESCC patients.In addition,further testing showed that the expression of IDO1 in patient samples from our hospital was positively correlated with its PD-L1 expression,but negatively correlated with the infiltration ratio of CD3/CD8 immune cells.Conclusion Tryptophan catabolism is associated with radiation resistance in ESCC,and the key enzyme IDO1 in tryptophan metabolism can be used as a therapeutic target for radiosensitization in ESCC.


Result Analysis
Print
Save
E-mail