1.Integrated evidence chain (Eff-iEC) based effectiveness evaluation of a multifunctional traditional Chinese medicine formula: Taking Xiaoyao San as an example
Caiping HE ; Ye LUO ; Zhiqi LI ; Haocheng YANG ; Lu LIU ; Yingjie XU ; Xiaoyan CHEN ; Siqi HUANG ; Jincai WEN ; Xiaoyan ZHAN ; Zhaofang BAI ; Xu ZHAO ; Xiaohe XIAO
Science of Traditional Chinese Medicine 2026;4(1):96-103
The study focuses on the concept of multifunctional traditional Chinese medicine (TCM) formulas and aims to evaluate the efficacy of the classical formula Xiaoyao San (逍遥散). Study employs the integrated evidence chain (Eff-iEC) method to organize, integrate, and evaluate its therapeutic efficacy in treating different diseases with the same therapy, and to investigate the feasibility of using Eff-iEC to evaluate the multifunctionality of TCM formulas. The evaluation covered Xiaoyao San's therapeutic effects on depression, premenstrual syndrome, chronic hepatitis, irritable bowel syndrome, dyspepsia, and menopausal syndrome. Concurrently, the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system was used for evaluation, and authoritative medical documents were incorporated to corroborate the recognition of Xiaoyao San within the medical community. Depression and menopausal syndrome received higher ratings than other conditions in the Eff-iEC, GRADE, and Medical Community Recognition assessments. The Eff-iEC evidence grade for Xiaoyao San was rated as "High" or above for chronic hepatitis, irritable bowel syndrome, dyspepsia, and menopausal syndrome. Premenstrual syndrome received a "Moderate +" rating. The GRADE evidence level was "Low-〇〇⨁⨁" for depression, premenstrual syndrome, and chronic hepatitis; "Moderate-〇⨁⨁⨁" for dyspepsia and menopausal syndrome; and "Very Low-〇〇〇⨁" for irritable bowel syndrome. Depression and menopausal syndrome had the highest inclusion frequency, appearing in all 4 categories. Premenstrual syndrome, chronic hepatitis, and dyspepsia are not recommended in Western medical guidelines, but they are included in TCM guidelines, the China National Basic Medical Insurance Drug List, and the China National Essential Drug List. Irritable bowel syndrome appears only in the China National Basic Medical Insurance Drug List and China National Essential Drug List. The evaluation results obtained using the Eff-iEC method align with Medical Community Recognition, providing an objective and comprehensive assessment of Xiaoyao San's efficacy. The findings suggest that Xiaoyao San has strong evidence for treating depression and menopausal syndrome. However, further experimental and clinical trials are needed to assess its efficacy in treating premenstrual syndrome, chronic hepatitis, irritable bowel syndrome, and dyspepsia. These results support the clinical efficacy and rational use of Xiaoyao San, expand the application scope of the Eff-iEC method, and offer valuable insights and methodological references for the comparative evaluation of multifunctional TCM formulas.
2.Serological characteristics of individuals with hepatitis C virus/hepatitis B virus overlapping infection
Yanfei CUI ; Xia HUANG ; Chao ZHANG ; Yingjie JI ; Song QING ; Yuanjie FU ; Jing ZHANG ; Li LIU ; Yongqian CHENG
Journal of Clinical Hepatology 2026;42(1):74-79
ObjectiveTo investigate the status of overlapping hepatitis B virus (HBV) infection in patients with chronic hepatitis C virus (HCV) infection and the serological characteristics of such patients. MethodsA total of 8 637 patients with HCV infection who were hospitalized from January 1, 2010 to December 31, 2020 and had complete data of HBV serological markers were enrolled, and the composition ratio of patients with overlapping HBV serological markers was analyzed among the patients with HCV infection. The patients were divided into groups based on age and year of birth, and serological characteristics were analyzed, and the distribution of HBV-related serological characteristics were analyzed across different HCV genotypes. ResultsThe patients with HCV/HBV overlapping infection accounted for 5.85%, and the patients with previous HBV infection accounted for 48.10%; the patients with protective immunity against HBV accounted for 14.67%, while the patients with a lack of protective immunity against HBV accounted for 31.39%. The patients were divided into groups based on age: in the 0 — 17 years group, the patients with protective immunity against HBV accounted for 61.41% (304 patients); the 18 — 44 years group was mainly composed of patients with previous HBV infection (698 patients, 37.31%), the 45 — 59 years group was predominantly composed of patients with previous HBV infection (1 945 patients, 50.38%), and the ≥60 years group was also predominantly composed of patients with previous HBV infection (1 486 patients, 61.66%). The patients were divided into groups based on the year of birth: in the pre-1992 group, the patients with previous HBV infection accounted for 51.63% (4 112 patients); in the 1992 — 2005 group, the patients with protective immunity against HBV accounted for 54.72% (168 patients); in the post-2005 group, the patients with protective immunity against HBV accounted for 64.38% (235 patients). In this study, 6 301 patients underwent HCV genotype testing: the patients with genotype 1b accounted for the highest proportion of 51.71% (3 258 patients), followed by those with genotype 2a (1 769 patients, 28.07%), genotype 3b (63 patients, 1.00%), genotype 3a (10 patients, 0.16%), genotype 4 (21 patients, 0.33%), and genotype 6a (5 patients, 0.08%). ConclusionWith the implementation of hepatitis B planned vaccination program in China, there has been a significant reduction in the proportion of patients with previous HBV infection among the patients with HCV/HBV overlapping infection, but there is still a relatively high proportion of patients with a lack of protective immunity against HBV.
3.Mechanism of Huazhuo Sanjie Chubi Presciption in Regulating Macrophage Polarization and Improving Low-grade Inflammation in Rats with Chronic Gouty Arthritis
Yuwan LI ; Yingjie ZHANG ; Siyuan LIN ; Xiaohua CHEN ; Qianglong CHEN ; Fan YANG ; Jun LIU ; Bingyan CHEN ; Peng CHEN ; Jiemei GUO ; Youxin SU ; Yan XIAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):93-104
ObjectiveTo evaluate the therapeutic effect of Huazhuo SanJie Chubi presciption (HSCD) on chronic gouty arthritis (CGA) rats with low-grade inflammation and to explore the underlying mechanism with a focus on macrophage polarization. MethodsThe 41 male 6-week-old SD rats were randomly allocated, using the random number table, to a normal group (n=8) and a model group (n =33). CGA with low-grade inflammation was induced in the model group by daily gavage of potassium oxonate (250 mg·kg-1·d-1) and hypoxanthine (300 mg·kg-1·d-1), combined with intra-articular injection of a monosodium urate (MSU) crystal suspension (50 μL, 25 g·L-¹) into the left ankle twice weekly. After 4 weeks of modeling, 3 rats were randomly selected from each group for model validation. The remaining successfully modeled rats were randomly divided into a model group, an HSCD group (10.35 g·kg-1·d-1, gavage once daily), an M1 polarization agonist group (L-methionine sulfoximine, 300 mg·kg-1, subcutaneous injection every other day), an M1 polarization agonist + HSCD group, an M2 polarization inhibitor group (PD0325901, 10 mg·kg-1·d-1, gavage once daily), and M2 polarization inhibitor + HSCD group. The corresponding drug or drug combination was administered according to group assignment, whereas rats in the normal and model groups received 0.5% carboxymethyl cellulose sodium (CMC-Na) vehicle (10.35 g·kg-1·d-1, gavage once daily). All interventions were continued for four weeks. During the intervention period, except for the normal group, potassium oxonate (250 mg·kg⁻¹) and hypoxanthine (300 mg·kg-1) were co-administered by gavage every other day to maintain the model. At the end of treatment, serum uric acid (SUA), ankle joint diameter and joint swelling index were measured. The levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), chemokine C-C motif ligand 2 (CCL2), S100 calcium-binding protein A8/A9 (S100A8/A9), interleukin-10 (IL-10) and arginase-1 (Arg-1) in serum and joint fluid were determined by enzyme-linked immunosorbent assay (ELISA). High-frequency ultrasound was used to assess MSU deposition in the ankle joint. Hematoxylin-eosin (HE) staining was performed to evaluate synovial histopathological changes. Quantitative Real-time PCR and immunofluorescence were used to detect the mRNA and protein expression of the M1 macrophage polarization markers inducible nitric oxide synthase (iNOS) and the M2 macrophage polarization marker scavenger receptor cysteine-rich type 1 protein M130 (CD163) in synovial tissue. ResultsCompared with the normal group, the model group showed significantly elevated SUA level and joint swelling index, and increased levels of pro-inflammatory cytokines, CCL2, and S100A8/A9 in both serum and joint fluid (P<0.05), accompanied by MSU deposition and synovial inflammation in the ankle joint. The mRNA and protein expression levels of macrophage polarization M1/M2 markers iNOS and CD163 in synovial tissues were also significantly up-regulated (P<0.05). Compared with model group, rats in HSCD group had significantly lower SUA levels, attenuated joint swelling, reduced serum levels of pro-inflammatory cytokines, and decreased levels of CCL2 and S100A8/A9 in both serum and joint fluid, accompanied with alleviated MSU deposition and synovial inflammation (P<0.05). HSCD markedly downregulated the mRNA and protein expression of M1 marker iNOS (P<0.05), whereas it had no significant effect on the expression of M2 marker CD163. Compared with the M1 polarization agonist group, the M1 polarization agonist + HSCD group showed significantly reduced joint swelling, lower serum levels of pro-inflammatory cytokines, and decreased levels of CCL2 and S100A8/A9 in joint fluid (P<0.05). In addition, synovial inflammatory cell infiltration and angiogenesis were attenuated, and iNOS mRNA and protein expression levels were significantly reduced (P<0.05). Compared with the M2 polarization inhibitor group, the M2 polarization inhibitor + HSCD group exhibited reduced joint swelling, decreased levels of CCL2 and S100A8/A9 in joint fluid and ameliorated synovial inflammation (P<0.05), whereas the levels of anti-inflammatory mediators (IL-10, Arg-1) and CD163 mRNA and protein expression were not significantly increased. ConclusionHSCD alleviates low-grade inflammation in CGA rats, at least in part, by inhibiting macrophage polarization toward the M1 phenotype.
4.Effect and Action Mechanism of Huazhuo Sanjie Chubi Prescription on Gouty Bone Erosion Model Rats Based on PI3K/Akt Signaling Pathway
Zhuoming ZHENG ; Jun LIU ; Meiling WANG ; Xiaohua CHEN ; Yuwan LI ; Siwei PENG ; Yingjie ZHANG ; Ruifang YANG ; Youxin SU ; Yan XIAO ; Jiemei GUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):105-117
ObjectiveThis paper aims to observe the effect of Huazhuo Sanjie Chubi prescription (HSCD) on the gouty bone erosion model rats and investigate its action mechanism. MethodsThirty-six two-month-old male SD rats were randomly divided into the blank group with nine rats and the modeling group with 27 rats. The rats in the modeling group were administered hypoxanthine solution at 300 mg·kg-1·d-1 and potassium oxonate solution at 250 mg·kg-1·d-1, combined with intra-articular injection of 200 μL monosodium urate (MSU) crystal suspension at 25 g·L-1 into the right ankle joint (joint injection once every three days), so as to induce the gouty bone erosion model. After four weeks of modeling, three rats were selected from these two groups to validate the model. The modeled 24 rats were randomly divided into the model group, HSCD group (10.35 g·kg-1·d-1), allopurinol group (20 mg·kg-1·d-1), and inhibitor group (LY294002, 10 mg·kg-1·d-1), with six rats per group. Except for the blank group, rats in all other groups continued to receive hypoxanthine solution at 300 mg·kg-1 and potassium oxonate solution at 250 mg·kg-1 via gavage concurrently with administration to maintain modeling intervention. The rats in the HSCD group and allopurinol group received administration by gavage at the above doses. The rats in the inhibitor group received an intraperitoneal injection at the above dose. The rats in the blank group and model group received saline (10.35 g·kg-1·d-1) by gavage for four consecutive weeks. After administration, ankle joint swelling of the rats in all groups was observed, and the diameters were measured. Bone volume fraction (BV/TV) and bone surface area to bone volume (BS/BV) were observed and quantitatively analyzed by Micro-CT. Histopathological changes in the ankle joint were observed by hematoxylin-eosin (HE) staining and safranin O-fast green staining. The uric acid in the rats' serum was determined by enzyme colorimetry. The levels of inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). The protein expressions of receptor activator of nuclear factor-κB ligand (RANKL) and phosphorylated (p)-phosphatidylinositol-3-kinase (PI3K) in ankle joint tissues of rats were detected by immunofluorescence staining. The mRNA levels of the proteins related to the bone erosion, including RANKL, tartrate-resistant acid phosphatase
5.WTAP enhances MAP3K9 mRNA stability via m6 A modification to promote malignant biological behaviors in esophageal squamous cell carcinoma cells
Yingjie PAN ; Shan SUN ; Hang YANG ; Jinsong TAN ; Qiaoling CHEN ; Quanneng ZHAO ; Mi YANG ; Kang LIU ; Guiqin SONG
Chinese Journal of Cancer Biotherapy 2025;32(2):140-150
Objective:To investigate the effects and molecular mechanisms of Wilms tumor 1-associated proteins(WTAP)on the cell biological properties of esophageal squamous cell carcinoma(ESCC)cells.Methods:31 pairs of ESCC tissues and their paired paracancerous tissues that were surgically resected at the Second Clinical Medical College of Chuanbei Medical College between September 2019 and April 2021 were collected.The esophageal cancer cells KYSE30,KYSE410,KYSE150,KYSE510,TE-1,and normal human esophageal epithelial cells HET-1A were routinely cultured.Transfection reagents were used to transfect si-NC,si-WTAP#1 and si-WTAP#2 nucleic acids into KYSE150 and KYSE510 cells.The cells were divided into si-NC,si-WTAP#1 and si-WTAP#2 groups.The expressions of WTAP and MAP3K9 mRNA were detected in the cells of each group by qPCR assay.CCK-8 assay,clone formation assay,and scratch healing assay,Transwell assay were employed to detect the effects of knockdown of WTAP expression on ESCC cell proliferation,migration,invasion and apoptosis.WB assay was used to detect the expressions of WTAP,MAP3K9,EMT and MAPK pathway-related proteins in ESCC cells of each group knocked down of WTAP;immunohistochemistry to detect the expression of WTAP proteins in ESCC tissues,immunoprecipitation of methylated RNA(MeRIP)-qPCR assay to detect the level of MAP3K9 m6A in ESCC cells,actinomycin D assay to detect the stability of mRNA of MAP3K9,and database data to analyze the expression,target genes,functional enrichment,and interacting RNA of WTAP.Results:WTAP was highly expressed in ESCC tissues and cells(P<0.05 or P<0.01 or P<0.001)and correlated with the degree of differentiation(P<0.01);the expression of WTAP mRNA and its protein were successfully knocked down in KYSE150 and KYSE510 cells(P<0.01 or P<0.001);the knockdown of WTAP significantly inhibited the proliferation,migration and invasion of KYSE150 and KYSE510 cells(P<0.05 or P<0.01 or P<0.001),and promoted the apoptosis of KYSE150 and KYSE510 cells(P<0.05 or P<0.01).Knockdown of WTAP resulted in a significant decrease in the m6A level of MAP3K9(P<0.05),and its mRNA expression level and mRNA stability were both significantly reduced(P<0.05).Database data analysis showed that WTAP target genes clustered in the MAPK signaling pathway;the expression levels of MAP3K9,p-ERK,N-cadherin,and MMP9 were significantly reduced(P<0.05 or P<0.01),and the expression level of E-cadherin was significantly elevated(P<0.05 or P<0.01)in the KYSE150 and KYSE510 cells after knockdown of WTAP.Conclusions:WTAP is highly expressed in ESCC tissues and cells and correlates with their differentiation.It promotes the stability of MAP3K9 mRNA through m6A modification,activates the MAPK pathway and thus promotes the malignant biological behaviors of ESCC cells.
6.Systematic review of readiness assessment tools for advance care planning in older adults
Yingjie PENG ; Aihong LIU ; Wenli ZHU ; Yuxin MEI ; Meng ZHOU ; Wenjing GUAN
Chinese Journal of Nursing 2025;60(9):1146-1152,后插1
Objective To systematically evaluate the advance care planning readiness assessment tools applicable to the elderly and to provide a reliable assessment tool for the development of advance care planning.Methods PubMed,Web of Science,Cochrane Library,Embase,CINAHL,Yimaitong,Wanfang Database,China National Know-ledge Network,VIP Database,and China Biomedical Literature Database were systematically searched.The search time limit is from database establishment to April 30,2024.Pre-established medical care plan readiness assessment tools that meet the inclusion criteria were screened,and the"consensus based standards for the selection of health measurement instruments"was used to evaluate the methodological quality and measurement attributes of the inclusion assessment tools.The improved version of the evidence quality evaluation and recommendation strength grading method is used to grade the evidence of the assessment tool and form the final recommendation opinion.Results A total of 14 articles were included,including 10 advance care planning readiness assessment tools suitable for the elderly.None of the articles reported cross-cultural validity,measurement error,and responsiveness.The content validity and internal consistency of the Chinese Advance Care Planning Readiness Scale and the Advance Care Planning Readiness Scale for Chronic Disease Patients were both"adequate",with A-level recommendations,and the remaining assessment tools were all B-level recommendations.Conclusion There are various types of advance care planning readiness assessment tools for the elderly,but the methodological quality needs to be improved and the measurement properties need to be further evaluated.It is temporarily recommended to use the Chinese Advance Care Planning Readiness Scale and the Advance Care Planning Readiness Scale for Chronic Disease Patients.
7.Research Progress of Flavonoids Derived from Forsythia against Respiratory Viruses
Jiaqing LIU ; Wei HONG ; Yingjie QING
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(11):1573-1584
Respiratory viruses,characterized by high mutation rates and strong immune evasion,remain a significant global public health challenge.Natural products have gained increasing attention due to their multi-target modulation and high safety profiles,dem-onstrating unique advantages in antiviral,anti-inflammatory,and immunoregulatory applications.Forsythia,a deciduous shrub of the Oleaceae family,possesses medicinal value in nearly all its parts,with flavonoids being among its most prominent bioactive compo-nents.This review provides a comprehensive summary of the botanical characteristics and traditional medicinal uses of Forsythia,the composition and structural classification of flavonoids from different parts of the plant,and its clinical applications.Building on the"holistic view"of traditional Chinese medicine,this review primarily discusses the antiviral mechanisms of Forsythia-derived flavo-noids in four key aspects:viral targeting,immune regulation,inflammation suppression,and post-viral syndrome.Additionally,it ana-lyzes its clinical application advantages and translational strategies,providing a basis for further development of new natural products and therapeutic drugs in clinical practice.
8.Research Paradigms and Methods in Integrated Imaging of Traditional Chinese and Western Medicine
Yingjie WU ; Nuan CUI ; Guojiang XIN ; Wanghua LIU ; Weixiong JIAN ; Hao LIANG
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(5):7-12
The integration of TCM and Western medicine in imaging aims to enrich the sources of diagnostic information by utilizing medical imaging technologies,focusing on key elements such as TCM imaging,Western medical imaging,diseases and TCM syndrome types,thereby facilitating the complementary strengths of both systems.With the advancement of digital imaging and artificial intelligence technologies,various research models and methodologies have emerged.This article discussed the development and application of integrated imaging of traditional Chinese and Western medicine,and proposed three primary research paradigms in this field:Analyzing TCM images(e.g.,tongue and face)through manual or image processing techniques to assist in the diagnosis of Western medical diagnosis;Mapping Western medical imaging signs(e.g.,computed tomography,magnetic resonance imaging and ultrasound imaging)to TCM syndrome patterns for objective evidence in TCM diagnosis and treatment;Applying imaging omics to extract and integrate features from both TCM and Western medical images for comprehensive diagnosis.This study reviewed the three paradigms,explained relevant concepts and technologies,and proposed a specific research workflow of integrated imaging omics of traditional Chinese and Western medicine,aiming to provide a reference for innovative development in this field.
9.Short-term outcome study on cervical deep lymph node-venous anastomosis technique in the treatment of Alzheimer’s disease
Cheng GAN ; Zhengdong KONG ; Xiaoye RAN ; Shudong QIAO ; Yixin ZHANG ; Lu YUE ; Yingjie WANG ; Hui BI ; Dong YANG ; Hongtong MA ; Yuan CHEN ; Hongli CHAI ; Ying JIA ; Chenhao MA ; Zixiang CHEN ; Ke LI ; Miao WANG ; Liguo XUE ; Siwen ZHAO ; Ke WEN ; Lin YIN ; Bo DING ; Shan ZHU ; Yuanbo LIU ; Mengqing ZANG
Chinese Journal of Plastic Surgery 2025;41(2):130-143
Objective:To explore the short-term clinical effects of deep cervical lymph node-venous anastomosis in the treatment of Alzheimer’s disease (AD).Methods:A prospective exploratory study was conducted on the treatment of AD patients using the cervical deep lymph node-venous anastomosis technique in Scar and Wound Treatment Department, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, from September to October 2024. The patients underwent high-frequency ultrasound to locate deep cervical lymph nodes and the external jugular vein. Under general anesthesia, bilateral deep cervical lymph node-venous anastomoses were performed. Indocyanine green (ICG) lymphography was conducted via subcutaneous injection behind the ear to visualize lymph nodes in levels Ⅱ and Ⅲ. After making a skin incision along the posterior margin of the sternocleidomastoid muscle, the external jugular vein, internal jugular veins, and associated lymph nodes were exposed. Adjacent veins were selected for anastomosis of lymph node. Using microsurgical techniques, end-to-side or end-to-end anastomosis was completed for lymph nodes in levels Ⅱ and Ⅲ. Preoperative assessments included the mini-mental state examination (MMSE, a higher score indicates better cognitive function), Alzheimer’s disease assessment scale-cognitive subscale (ADAS-Cog, a higher score indicates greater impairment of cognitive function), Alzheimer’s disease cooperative study scale for activities of daily living (ADCS-ADL, a higher score indicates better ability to perform daily activity), and neuropsychiatric inventory (NPI, a higher score indicates more severe behavioral and emotional symptom). Postoperative follow-up included the same scales to observe changes in cognitive function, activities of daily living, and emotional communication.Results:Four patients (1 male, 3 females, aged 58-79 years) with AD were included. All were diagnosed based on cerebrospinal fluid biomarkers. All patients successfully underwent bilateral deep cervical lymph node-venous anastomoses. On average, 4.3 (2-7 per person) anastomoses were performed per patient. Surgical procedures lasted an average of 6.5 h (5.5-8.5 h) with minimal blood loss (less than 50 ml). Patients resumed normal activity within 6 hours postoperatively and were discharged after an average of 4.1 d (3.5-5.0 d). Postoperative complications included one case each of aspiration pneumonia, lower limb venous thrombosis, and transient delirium, all of whom resolved without long-term effects. Clinical symptoms, including memory decline, mood swings, and anxiety, showed varying degrees of improvement. Patients reported enhanced quality of life, emotional stability, and social engagement, confirming the procedure’s safety and potential cognitive benefits. At one month postoperatively, the MMSE scores of the four patients increased by an average of 0.8 points compared to preoperative levels. Additionally, the two patients who completed the ADAS-Cog assessments showed a decrease in their scores (reduced by 1.0 points and 11.3 points, respectively, compared to preoperative scores), indicating a certain degree of improvement in cognitive function during this period. The ADCS-ADL and NPI scores of four patients varied significantly, without showing any clear pattern.Conclusion:Lymphovenous anastomosis of the deep cervical lymph node-venous anastomosis may provide a new surgical intervention approach for AD, but further large-scale studies and long-term follow-up are needed to validate its safety and effectiveness.
10.Construction of prognostic risk model for renal cell carcinoma based on lactate metabolism-related genes and analysis of immune characteristics of renal cell carcinoma
Zhijia SUN ; Zhuo SONG ; Xu LIU ; Xiaoli KANG ; Xinji LI ; Yingjie WANG
Chinese Journal of Microbiology and Immunology 2025;45(11):949-957
Objective:To construct a prognostic risk model based on lactate metabolism-related genes screened using bioinformatics methods in renal cell carcinoma patients,and investigate the clinical prognosis and immune characteristics of renal cell carcinoma.Methods:Gene expression data and clinical information of patients with renal cell carcinoma were downloaded from the Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma(TCGA-KIRC)dataset. Lactate metabolism-related gene sets were obtained from the Gene Set Enrichment Analysis(GSEA)database. The R package DEseq2 was employed to identify differentially expressed genes associated with lactate metabolism within the TCGA-KIRC dataset. GO and KEGG enrichment analyses were performed using the clusterProfiler package. Prognosis-related genes were screened via univariate Cox regression analysis and the intersection with lactate metabolism-related differentially expressed genes was obtained. A risk model was constructed using LASSO regression followed by multivariate Cox regression analysis to calculate risk scores. This risk model was subsequently validated using the GSE29609 dataset. Patients were stratified into high-risk and low-risk groups based on the median risk score. The expression profiles of key immune molecule genes and immune checkpoint genes were compared between the two groups. Survival analysis curves for immune checkpoint genes were generated using the survival and survminer R packages. Differences in tumor mutation burden(TMB)between the high-risk and low-risk groups were assessed,and corresponding TMB survival analysis curves were plotted. Finally,the tumor immune dysfunction and exclusion(TIDE)algorithm was used to evaluate disparities in immunotherapy response potential between the two risk groups.Results:An optimal prognostic risk model incorporating seven lactate metabolism- and prognosis-related genes( LDHD,PER2,ACADM,FLI1,LIPA,TCIRG1,SLC25A4)was constructed and successfully validated in the GSE29609 dataset. Univariate Cox regression analysis revealed that a high-risk score was significantly associated with poor prognosis( HR=2.915,95% CI:2.451-3.470, P<0.001). Multivariate Cox regression analysis confirmed that this risk model could serve as an independent prognostic factor for patients with renal cell carcinoma( HR=2.231,95% CI:1.829-2.722, P<0.001). Patients in the high-risk group exhibited significantly worse outcomes compared to the low-risk group,regardless of whether they had early-stage or advanced-stage renal cell carcinoma(both P<0.001). Analyses related to the immune microenvironment indicated an upregulated immunosuppressive phenotype in the high-risk group. Furthermore,the TMB was significantly higher in the high-risk group than in the low-risk group( P=0.032),and patients within the high-risk group exhibiting higher TMB levels demonstrated even poorer survival( P<0.001). Finally,the TIDE score was significantly elevated in the high-risk group in comparison to the low-risk group( P<0.001). Conclusions:The risk model based on lactate metabolism-related genes constructed in this study can guide the prognosis of renal cell carcinoma. Patients in the high-risk group are more prone to immune escape and formation of an inhibitory immune microenvironment,leading to worse prognoses. This risk model may serve as a biomarker for predicting immunotherapy response.

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