1.Discovery of a potential hematologic malignancies therapy: Selective and potent HDAC7 PROTAC degrader targeting non-enzymatic function.
Yuheng JIN ; Xuxin QI ; Xiaoli YU ; Xirui CHENG ; Boya CHEN ; Mingfei WU ; Jingyu ZHANG ; Hao YIN ; Yang LU ; Yihui ZHOU ; Ao PANG ; Yushen LIN ; Li JIANG ; Qiuqiu SHI ; Shuangshuang GENG ; Yubo ZHOU ; Xiaojun YAO ; Linjie LI ; Haiting DUAN ; Jinxin CHE ; Ji CAO ; Qiaojun HE ; Xiaowu DONG
Acta Pharmaceutica Sinica B 2025;15(3):1659-1679
HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.
2.Precision-driven imaging assessment of traumatic fractures in the era of personalized medicine
Xuan WEI ; Yeming ZHONG ; Zigang CHE ; Yuchen CHEN ; Hao WANG ; Pengfei ZHAO
Chinese Journal of Medical Aesthetics and Cosmetology 2025;31(4):343-347
Traumatic injuries represent the fifth leading cause of death in China and the primary cause of death among young adults. While facial fractures can lead to significant aesthetic and psychological consequences, fractures in the limbs and joints impair functional mobility. In traumatic incidents requiring forensic evaluation, such as traffic accidents or violent conflicts, the type and severity of fractures directly determine injury grading and disability assessment. Consequently, the accurate diagnosis of traumatic fractures is not only a critical medical issue impacting patient management and rehabilitation but also a significant social issue influencing judicial fairness. This article systematically reviews advancements in multi-modal imaging techniques. While conventional X-ray radiography remains a fundamental screening tool, it faces challenges in detecting occult fractures. Multi-slice spiral computed tomography (MSCT), utilizing 3D reconstruction, enables spatial analysis of complex fractures. Magnetic resonance imaging (MRI), with its multi-sequence capabilities, plays an indispensable role in detecting bone marrow edema and assessing concomitant soft tissue injuries. Regarding innovative technologies, dual-energy computed tomography (DECT) employs virtual non-calcium (VNC) techniques for quantitative bone marrow edema analysis; ultra-high-resolution computed tomography (U-HRCT) breaks through imaging limitations of trabecular microarchitecture with a resolution of approximately 10 μm; and 7.0 T ultra-high-field MRI, alongside MRI-based CT-like imaging techniques, advances radiation-free bone structure evaluation. Artificial intelligence (AI) models significantly enhance diagnostic efficiency in fracture detection. Future developments will focus on multi-modal image fusion, the construction of intelligent decision-support systems, and the quantitative functional assessment of bone microstructure, facilitating a paradigm shift from anatomical description to prognostic prediction and realizing the principles of personalized medicine.
3.Correlation between mental health status and metabolic syndrome in health checkup population
Honghai HE ; Xiaolian ZHANG ; Xiaoyan HAO ; Ying CHE ; Wei ZHAO ; Hongli WANG ; Lei TIAN ; Hua WU ; Peng WANG
Chinese Journal of Health Management 2025;19(2):127-133
Objective:To analyze the correlation between mental health status and metabolic syndrome (MetS) in health checkup people.Methods:It was a cross-sectional study, 2 920 participants who received health checkup in the Health Examination Center of Peking University Third Hospital from January 2019 to December 2023 were selected using cluster sampling method. Their general information, physical examination, biochemical indicators, body composition, and self-evaluation scores on the Symptom Checklist-90 (SCL-90) were collected. According to the inclusion and exclusion criteria, a total of 2 813 study subjects were included, and divided into the MetS group and the non-MetS group based on whether they had MetS. The differences in general demographic information, body composition, blood biochemistry, and SCL-90 scores between the two groups were compared. Binary Logistic regression analysis was used to explore the correlation between mental health status and MetS.Results:Of the 2 813 subjects included, 1 576 were males (56.0%) and 1 237 were females (44.0%), with an average age of (41.7±11.0) years, the MetS group had 586 cases (20.8%) and the non-MetS group had 2 227 cases (79.2%). The MetS group had higher levels of age, body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, total cholesterol, triglycerides, low density lipoprotein cholesterol (LDL-C), fasting blood glucose, glycosylated hemoglobin (HbA 1c), free thyroxine(FT4), total triiodothyronine (TT3), free triiodothyronine (FT3), waist-to-hip ratio, visceral fat area, body fat percentage, uric acid/creatinine, homocysteine (Hcy), aspartate aminotransferases (AST), and alanine transaminase (ALT) levels, as well as higher scores for somatization, hostility, paranoia, and other factor compared to the non-MetS group (all P<0.05), while high density lipoprotein cholesterol (HDL-C) and estimated glomerular filtration rate (eGFR) levels were lower than those in the non-MetS group (all P<0.05). The proportion of male, and the positive rates of SCL-90, somatization, interpersonal sensitivity, hostility, paranoia and other factor in the MetS group were higher than those in the non-MetS group (all P<0.05). Multifactorial analysis showed that individuals with a positive SCL-90 assessment had a 1.34 times higher risk of MetS than those with a negative assessment ( OR=1.34, 95% CI: 1.06-1.68; P=0.014). Among them, individuals with positive somatization ( OR=2.02, 95% CI: 1.25-3.28; P=0.004) and hostility ( OR=1.61, 95% CI: 1.02-2.56; P=0.042) had increased risk of MetS. Conclusion:Poor mental health status increases the risk of MetS.
4.Correlation between normalized grip strength and normal weight obesity in health check-up population
Honghai HE ; Xiaolian ZHANG ; Xiaoyan HAO ; Wei ZHAO ; Peng WANG ; Ying CHE
Chinese Journal of Health Management 2025;19(4):273-278
Objective:To explore the correlation between normalized grip strength (NGS) and normal weight obesity (NWO) in the population undergoing health check-ups.Methods:It was a cross-sectional study. A cluster sampling method was adopted to consecutively select 4 104 subjects who completed general health check-ups, body composition tests, and grip strength tests at the Medical Examination Center of Peking University Third Hospital from January 2019 to December 2023. The general information, physical examination results, biochemical indicators, body composition, and grip strength test results were collected. The subjects were grouped by gender and whether they had NWO (male: NWO group 314 cases, normal control group 690 cases; female: NWO group 834 cases, normal control group 2 266 cases). The differences in various indicators between the NWO group and the normal control group were compared by using t-tests, χ 2 tests, or Mann-Whitney U tests. The subjects were divided into four groups with the quartiles of NGS (Q 1-Q 4 groups), and binary logistic regression analysis was used to explore the correlation between the NGS and NWO. The receiver operating characteristic (ROC) curve was used to evaluate the optimal cut-off point of the NGS for diagnosing NWO. Results:Among the 4 104 subjects included in the analysis, 1 148 (28.0%) had NWO. The risk of NWO in both males and females increased with the decrease of NGS. Compared with the Q 4 group, the risk of NWO in the Q 2 and Q 1 groups of males increased by 2.600 times ( OR=2.600, 95% CI:1.556-4.343) and 4.350 times ( OR=4.350, 95% CI: 2.618-7.229), respectively; the risk of NWO in the Q 3, Q 2, and Q 1 groups of females increased by 2.024 times ( OR=2.024, 95% CI: 1.322-3.099), 4.265 times ( OR=4.265, 95% CI: 2.856-6.371), and 7.395 times ( OR=7.395, 95% CI: 4.991-10.956), respectively (all P<0.05). The optimal cut-off point of the NGS for diagnosing NWO in males and females was 0.636 2 and 0.472 2, respectively. Conclusions:The NGS is negatively correlated with the risk of NWO. Evaluation of the NGS can provide a reference for the early diagnosis and prevention of NWO.
5.Construction and effect evaluation of group health management mode for functional community
Ying CHE ; Gaili HE ; Honghai HE ; Peng WANG ; Lei TIAN ; Wei ZHAO ; Zhenge ZHANG ; Xiaoyan HAO
Chinese Journal of Health Management 2025;19(10):815-822
Objective:To construct a health management mode for functional community groups and evaluate its health management effect.Methods:This study was a non-randomized controlled trial. A cluster sampling method was adopted to select 3 352 subjects who completed three health examinations at the Physical Examination Center of Peking University Third Hospital from January 2022 to October 2024 and received health management for two consecutive years from a certain functional community (an enterprise) in Beijing as the research subjects. A health management mode for functional community groups was constructed, and a cohort of the population was established. A health management platform was built, and the research subjects were included in the health management system. Comprehensive interventions were carried out using multiple methods, including disease risk assessment, daily monitoring and reminders, exercise and nutrition assessment and intervention, personal health consultation, and health science popularization knowledge push. The subjects were classified and analyzed based on general information such as age and gender. The changes in systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were assessed using One-way Repeated Measures Analysis of Variance before the intervention and at 1 and 2 years after the intervention. The changes in triglycerides were assessed using Generalized Estimating Equations before the intervention and at 1 and 2 years after the intervention.Results:The systolic blood pressure, total cholesterol, and LDL-C levels of the total population showed a linear decreasing trend after the intervention (all P0.001). The HDL-C level showed an overall upward trend after the intervention [(1.45±0.32) vs (1.39±0.30) vs (1.47±0.33) mmol/L, F=12.746, P0.001]. However, there was no linear change trend in diastolic blood pressure, fasting blood glucose, and triglycerides after the intervention (all P0.05). The systolic blood pressure, total cholesterol and LDL-C levels of both men and women showed a linear decreasing trend after the intervention. For men, systolic blood pressure [(128.6±16.1) vs (127.6±16.3) vs (126.5±15.5) mmHg (1 mmHg=0.133 kPa); F=33.488, P0.001], total cholesterol [(5.29±1.02) vs (5.07±1.00) vs (4.94±1.03) mmol/L; F=286.525, P0.001], and LDL-C [(3.45±0.86) vs (3.43±0.84) vs (3.33±0.83) mmol/L; F=55.419, P0.001] all decreased. For women, systolic blood pressure [(118.9±15.6) vs (117.5±15.6) vs (117.2±15.8) mmHg; F=34.188, P0.001], total cholesterol [(5.13±0.94) vs (4.96±0.90) vs (4.85±0.90) mmol/L; F=274.080, P0.001], and LDL-C [(3.13±0.79) vs (3.10±0.76) vs (3.10±0.75) mmol/L; F=6.861, P=0.009] also decreased. The HDL-C level of men showed an overall upward trend after the intervention [(1.30±0.26) vs (1.25±0.25) vs (1.32±0.28) mmol/L; F=6.866, P0.05]. For men and women, diastolic blood pressure, fasting blood glucose and triglyceride levels showed no linear change trend after the intervention (all P0.05). The systolic blood pressure and total cholesterol levels of all age groups showed a linear decreasing trend after the intervention(all P0.001). In the 50-59 age group, diastolic blood pressure showed a linear decreasing trend after intervention [(81.6±11.6) vs (80.1±11.6) vs (79.9±11.6) mmHg; F=7.043, P0.05]. In the 40-49 age group, triglyceride showed an overall decreasing trend after intervention [1.29(0.91-2.01) vs 1.27(0.88-1.91) vs 1.27(0.92-1.89) mmol/L; Wald χ 2=10.062, P0.05]. In the 30-39 age group, LDL-C showed a linear decreasing trend after intervention [(3.23±0.80) vs (3.20±0.79) vs (3.19±0.77) mmol/L; F=7.702, P0.05]. In the 40-49 age group, LDL-C also showed a linear decreasing trend after intervention [(3.39±0.84) vs (3.36±0.82) vs (3.30±0.80) mmol/L; F=22.801, P0.001]. In the 50-59 age group, LDL-C showed a linear decreasing trend after intervention [(3.38±0.92) vs (3.32±0.91) vs (3.15±0.88) mmol/L; F=27.920, P0.001]. In the 30-39 age group, HDL-C showed an overall increasing trend after intervention [(1.46±0.33) vs (1.39±0.31) vs (1.48±0.34) mmol/L; F=10.047, P0.05]. In the 40-49 age group, HDL-C also showed an overall increasing trend after intervention [(1.45±0.30) vs (1.40±0.30) vs (1.47±0.32) mmol/L; F=10.118, P0.05]. However, there was no linear change trend in fasting blood glucose and triglyceride levels in all age groups after intervention ( F=1.169, 2.643, 0.663, 0.001, all P0.05). Conclusion:The functional community group health management mode constructed in this study has a good effect.
6.DiaSphere embolized microsphere TACE for treating primary hepatocellular carcinoma:A prospective multicenter randomized controlled study
Hang YAO ; Hongtao HU ; Huicun CAO ; Xinwei HAN ; Jian ZHANG ; Weifu LYU ; Huanzhang NIU ; Hongyuan LIANG ; Hao XU ; Wentao LI ; Wei ZHAO ; Haibo CHE ; Yinghua ZOU
Chinese Journal of Interventional Imaging and Therapy 2025;22(6):375-379
Objective To observe the effectiveness and safety of DiaSphere embolized microsphere TACE for treating primary hepatocellular carcinoma(HCC).Methods Totally 188 patients with HCC were prospectively enrolled and randomly assigned to research group(n=93)and control group(n=95),who underwent TACE with DiaSphere embolized microspheres and Embosphere embolized microspheres,respectively.The incidence of TACE-related adverse events were recorded.The therapeutic efficacy 1 month after the first TACE,also 1 and 3 months after the last TACE,and liver functions 1 month after the first and last TACE were compared between groups.Results In research group,there were 69 cases underwent 1 time TACE,22 cases underwent 2 times and 2 cases underwent 3 times TACE,while in control group,there were 82 cases underwent 1 time and 13 cases underwent 2 times TACE,respectively.No statistical difference of the incidence of adverse events was found between groups(77.42%[72/93]vs.76.84%[73/95],P=1.000).One month after the first TACE,7 cases in research group and 11 cases in control group were lost to follow-up,respectively.One month after the last TACE,12 cases were lost to follow-up in both groups,and 3 months after the last TACE,28 cases were lost to follow-up in both groups.No significant difference of objective response rate nor disease control rate was found between groups at the above time points(all P>0.05).One month after the first and last TACE,liver function indicators were not different between groups(all P>0.05).Conclusion Both the short-term efficacy and safety of TACE with DiaSphere embolized microspheres for treating HCC were good.
7.Expert consensus on non-surgical treatment for acute lateral ankle sprain (version 2025)
Hui CHE ; Wenge DING ; Shiming FENG ; Xueping GU ; Qinwei GUO ; Jianchao GUI ; Yinghui HUA ; Yuefeng HAO ; Qinglin HAN ; Bo HU ; Xiaojun LIANG ; Guoping LI ; Yunxia LI ; Qi LI ; Yanlin LI ; Xin MA ; Jun MA ; Xudong MIAO ; Jianzhong QIN ; Xiaodong QIN ; Xu SUN ; Kefu SUN ; Weidong SONG ; Dai SHI ; Zhongmin SHI ; Youlun TAO ; Xu WANG ; Youhua WANG ; Liheng WANG ; Anli WANG ; Aiguo WANG ; Weidong WU ; Yajun XU ; Weidong XU ; Renjie XU ; Yongsheng XU ; Tengbo YU ; Lianqi YAN ; Xiaodong YUAN ; Yuan ZHU ; Mingzhu ZHANG ; Hongtao ZHANG ; Xintao ZHANG ; Xiaofei ZHENG
Chinese Journal of Trauma 2025;41(6):517-529
Acute lateral ankle sprain (ALAS) is one of the most common sport injuries, with high incidence, recurrence and disability rates. Currently, exercise rehabilitation-based non-surgical treatment is the primary management approach for ALAS. However, there remain improper practices such as excessive immobilization or uncontrolled activity, which contribute to recurrent sprains and chronic ankle instability, significantly impairing patients′ athletic function and quality of life. To standardize the non-surgical management of ALAS, improve the cure rates, and reduce the recurrence and disability rates, Chinese Sports Rehabilitation Medicine Training Project of Chinese Medical Association, Foot and Ankle Basics and Orthopedics Group, Orthopedic Branch of Chinese Medical Doctor Association, and Sports Medicine Branch of Jiangsu Medical Association organized relevant experts to formulate Expert consensus on non-surgical treatment for acute lateral ankle sprain ( version 2025), following the principles of scientific vigor, practicality, and innovation. Thirteen recommendations were proposed for standardized treatment protocols across different healing phases, aiming to provide references for standard management of ALAS and improve the therapeutic outcomes.
8.Construction and validation of prediction models for delayed encephalopathy after acute carbon monoxide poisoning based on machine learning
Yanwu YU ; Yan ZHANG ; Ding YUAN ; Huihui HAO ; Fang YANG ; Hongyi YAN ; Pin JIANG ; Mengnan GUO ; Zhigao XU ; Changhua SUN ; Gaiqin YAN ; Lu CHE ; Jianjun GUO ; Jihong CHEN ; Yan LI ; Yanxia GAO
Chinese Journal of Emergency Medicine 2025;34(10):1403-1409
Objective:s To investigate the risk factors for delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) in patients with acute carbon monoxide poisoning (ACOP) and to develop predictive models based on machine learning algorithms.Methods:Patients with ACOP hospitalized at the First Affiliated Hospital of Zhengzhou University from August 2019 to October 2024 were included, with the occurrence of DEACMP as the outcome measure. The dataset was randomly divided into training and validation sets at a ratio of 7:3. Lasso regression was used to select features influencing the outcome in training sets. Nine machine learning models—including Random Forest (RF), Extreme Gradient Boosting (XGBoost), and Support Vector Machine (SVM)—were constructed. Receiver operating characteristic (ROC) curves were plotted and the area under the curve (AUC) calculated for each model. Calibration curves were used to assess accuracy, and decision curve analysis (DCA) was applied to evaluate clinical utility. The SHapley Additive exPlanations (SHAP) method was employed to visualize and interpret the best-performing model.Results:A total of 264 ACOP patients were included, of whom 54 (20.5%) developed DEACMP. Lasso regression identified eight key feature variables. Based on these factors, predictive models were constructed, showing good AUC stability across the nine machine learning models in both training (0.92–0.99) and validation sets (0.85–0.91). The RF model performed best, with an AUC of 0.99 in the training set and 0.90 in the validation set; its calibration curve and DCA curve also demonstrated excellent performance. SHAP analysis of the RF model revealed the importance ranking of factors from highest to lowest as follows: Glasgow Coma Scale (GCS) score, duration of coma, age, history of coronary heart disease, CK-MB level, monocyte count, diastolic blood pressure (DBP), and drinking history.Conclusions:The RF model exhibited the highest predictive performance for DEACMP occurrence in ACOP patients. The influencing factors, ranked in order of importance from highest to lowest, are as follows: GCS score, duration of coma, age, history of coronary heart disease, CK-MB level, monocyte count, DBP, and drinking history.
9.Carotid artery stenting via transradial approach using single-layer braided microporous dense mesh stents:practical experiences from ten single-center cases
Xiangming XU ; Fengjun MAO ; Junjie SAI ; Yu LIANG ; Yansen CUI ; Hao WANG ; Fengyuan CHE
Chinese Journal of Cerebrovascular Diseases 2025;22(8):557-565
Objective To investigate the feasibility and safety of transradial approach(TRA)for carotid artery stenting(CAS)using single-layer braided carotid stents with a microporous dense mesh design.Methods A retrospective consecutive series of patients with carotid artery stenosis who underwent CAS via TRA using single-layer braided microporous dense mesh stents admitted to the Department of Neurology,Linyi People's Hospital,Shandong Second Medical University were included from December 2022 to April 2023.General and clinical data,lesion characteristics,procedural metrics,periprocedural conditions,and follow-up outcomes were collected from the patients.General and clinical data including sex,age,medical history(hypertension,diabetes,coronary artery disease),and preoperative modified Rankin scale(mRS)score.Lesion characteristics included stenosis location,normal lumen diameters distal and proximal to the stenosis,stenosis rate,lesion length,and aortic arch type.Procedural metrics included successfully guided catheter placement,stent deployment,retrieval of the embolic protection device and residual stenosis rate.Periprocedural conditions included periprocedural complications(within 72 hours included puncture site bleeding,symptomatic radial artery occlusion,new cerebral infarctions on diffusion-weighted imaging,and cardio-cerebrovascular events[angina,acute myocardial infarction,cerebral infarction,cerebral hemorrhage])and length of hospital stay.The mRS scores at 1 and 6 months after surgery were recorded via telephone follow-ups.At 12 months after surgery,outpatient carotid color Doppler ultrasound was performed to evaluate in-stent restenosis.Results(1)Ten patients(9 male,1 female)aged 57-72 years,with a median age of 70(62,71)years were included.Among them,9 had hypertension,2 had diabetes,and 1 had coronary artery disease.Four patients had symptomatic carotid stenosis:2 presented with hemiparesis,1 with mild dysarthria,and 1 with transient ischemic attack.Preoperative mRS scores among symptomatic patients were 0(1 patient),1(2 patients),and 2(1 patient).The remaining 6 patients had asymptomatic stenosis,all with preoperative mRS scores of 0.(2)Two patients had left internal carotid artery(ICA)stenosis,and 8 had right ICA stenosis.The mean stenosis degree was(79.9±7.1)%,and the mean lesion length was(16.8±5.7)mm.The mean normal distal and proximal lumen diameter of the stenosed blood vessel were(5.1±0.5)mm and(8.1±0.8)mm,respectively.One patient had a type Ⅰ aortic arch,8 patients had type Ⅱ,and 1 patient had type Ⅲ.Among the 8 patients with right ICA stenosis,4 underwent direct catheterization of the right common carotid artery using a glidewire,while the other 4 required exchange technique for guide catheter placement.Both left-sided lesions were treated using exchange technique.Guide catheter placement and stent deployment were successful in all cases.No difficulties were encountered in embolic protection device retrieval.The mean residual stenosis rate was(21.6±6.7)%.(3)The mean postoperative hospital stay was(1.8±0.9)days.No puncture site bleeding or symptomatic radial artery occlusion occurred.One patient experienced a cerebrovascular event due to a pontine perforator artery infarction,presenting with diplopia and impaired left eye adduction,likely caused by postoperative hypotension and hypoperfusion.This patient had an immediate postoperative mRS score of 2 at discharge,which improved to 0 at 6 months.The other 9 patients showed no change in mRS scores compared to preoperative assessments,and no new cerebral infarctions were detected within 72 hours after surgery.At 12-month follow-up,carotid color Doppler ultrasound revealed no in-stent restenosis in any patient.Conclusions CAS performed via TRA using single-layer braided microporous dense mesh stents appears to be feasible and safe.However,this study is a single-center,retrospective analysis with a small sample size.Larger prospective randomized controlled trials are needed to validate these findings.
10.Integrating Single-cell RNA Sequencing and Mendelian Randomization Reveals the Pathogenic Mechanism of Eomes in Renal Cell Carcinoma
Xin-cen WANG ; Hai-xia HUANG ; Xin-hao WANG ; Zhi-fei CHE ; Pei-yu LIANG
Progress in Modern Biomedicine 2025;25(15):2421-2430
Objective:This study employs a combination of single-cell sequencing and Mendelian randomization to explore the genetic associations and molecular mechanisms of Eomes in RCC.Methods:In this study,single-cell transcriptomic data from RCC tissues and adjacent normal tissues were extracted from the GEO database.The data were analyzed using R language and various packages such as Seurat,limma,and CellChat for cell cluster annotation,intercellular communication analysis,and differential expression analysis.Additionally,eQTL data related to differentially expressed genes were retrieved from the GWAS database as exposure variables,with RCC used as the outcome variable in Mendelian randomization analysis to identify the role of Eomes in RCC.Finally,GO functional enrichment and KEGG pathway analyses were conducted to explore the potential molecular mechanisms of Eomes.Results:Single-cell RNA sequencing revealed that B cells play a significant role in the heterogeneity of RCC.Mendelian randomization analysis indicated that Eomes is an important risk factor for RCC(P<0.05).Furthermore,seven highly correlated specific SNPs were identified,including rs 17021298,rs2247056,rs2617170,rs3806624,rs55908509,rs6590334,and rs9420589.GO and KEGG enrichment analyses suggest that Eomes may be involved in early cell fate determination in renal cell carcinoma and participate in the regulation of Th1 and Th2 cell differentiation,HPV infection,and the Notch signaling pathway.Conclusions:This study is the first to combine single-cell sequencing and Mendelian randomization analysis in RCC,confirming a strong positive causal relationship between Eomes and RCC(OR>1).Our findings offer new insights into the pathogenesis of RCC,suggesting that Eomes could serve as a novel target for early diagnosis and personalized treatment of RCC.

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