1.The prognostic value and immune regulatory role of BRF1 in pan-cancer, and its function in esophageal squamous cell carcinoma
Jianxin XU ; Zihao LI ; Wang LÜ ; ; Zhiyang XU ; Yunfeng YI ; Songlin CHEN ; Jian HU ; Luming WANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(01):122-131
Objective To investigate the expression profile, prognostic value, gene co-expression network, and immunomodulatory role of BRF1 in a pan-cancer context, and to explore its biological functions and molecular regulatory mechanisms in esophageal squamous cell carcinoma (ESCC). Methods The pan-cancer dataset from The Cancer Genome Atlas (TCGA) was utilized to analyze the differential expression of BRF1 in tumor versus normal tissues, its association with patient survival, pathway enrichment for co-expressed genes, and immune features (including immune checkpoints, cytokines, and immune cell infiltration). The expression profile of BRF1 in ESCC was validated using the Gene Expression Omnibus (GEO) database. In vitro, BRF1 was knocked down in ESCC cells using siRNA. Cell proliferation and migration were assessed by MTT and Transwell assays, respectively. The expression levels of proliferation- and migration-related proteins were detected by Western blotting. The correlation between BRF1 and ferroptosis was analyzed using TCGA data. Results BRF1 was significantly upregulated in over 20 types of cancer, and its high expression was associated with poor prognosis in patients with adrenocortical carcinoma and prostate adenocarcinoma. BRF1 was found to positively regulate the T-cell-mediated cell death pathway in esophageal adenocarcinoma and was associated with the circadian rhythm regulation pathway in pancreatic adenocarcinoma. The correlation of BRF1 with immune checkpoints, cytokine networks, and immune cell infiltration was found to be cancer type-specific. In vitro experiments demonstrated that knocking down BRF1 significantly inhibited the proliferation of ESCC cells, accompanied by the downregulation of the proliferation marker PCNA. Cell migration was also significantly impaired, with decreased expression of Vimentin and MMPs and increased expression of E-cadherin. Furthermore, the expression of BRF1 was positively correlated with that of ferroptosis-antagonizing genes, such as GPX4, HSPA5, and SLC7A11. Conclusion BRF1 plays complex roles in pan-cancer, participating in the regulation of tumorigenesis, progression, and immune infiltration. BRF1 promotes the proliferation and migration of ESCC cells, a mechanism potentially associated with the regulation of ferroptosis resistance. These findings suggest that BRF1 could be a potential therapeutic target for ESCC.
2.Construction and clinical application exploration of an artificial intelligence-based high-quality lung cancer surgery dataset
Xuhua HUANG ; Yunfeng NIE ; Liang SHEN ; Pengxu KONG ; Xin TAN ; Zihao LI ; Wang LV ; Min ZHOU ; Xudong LV ; Jian HU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(05):717-727
Objective To construct a lung cancer surgery-oriented disease-specific database covering the entire perioperative care pathway, thereby improving the quality and usability of key surgical data elements. Methods Real-world clinical data were extracted from a single-center thoracic surgery department. A standardized data model was established based on the open electronic health record (openEHR) standard. Large language model (LLM), optical character recognition (OCR), and artificial intelligence (AI)-driven techniques were employed to extract, structure, and perform quality control on unstructured clinical narratives, imaging reports, and radiological data, with a focus on capturing surgically relevant perioperative indicator. Results A multimodal database comprising 19 917 patients was established, including 7 930 males and 11 987 females, with ages ranging from 15 to 97 (61.7±9.7) years. The database includes 582 structured data variables, textual report data corresponding to 69 clinical indicators, 13 000 pulmonary function test PDF reports, and chest CT imaging data from 16 884 patients. This database comprehensively covers major information relevant to surgical diagnosis and treatment of lung cancer, significantly improving the completeness and granularity of surgical detail data. Large language models (LLMs) and optical character recognition (OCR) technologies enhanced the efficiency of converting unstructured data into structured formats, while a multi-level manual verification process ensured data accuracy and traceability. The database supports real-world research including comparisons of surgical procedures, prediction of postoperative complications, prognosis assessment, and multimodal data association analyses.
3.Comprehensive evaluation of benign and malignant pulmonary nodules using combined biological testing and imaging assessment in 1 017 patients: A retrospective cohort study
Lei ZHANG ; Zihao LI ; Nan LI ; Jun CHENG ; Feng ZHANG ; Pinghui XIA ; Wang LÜ ; ; Jian HU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(01):60-66
Objective By combining biological detection and imaging evaluation, a clinical prediction model is constructed based on a large cohort to improve the accuracy of distinguishing between benign and malignant pulmonary nodules. Methods A retrospective analysis was conducted on the clinical data of the 32 627 patients with pulmonary nodules who underwent chest CT and testing for 7 types of lung cancer-related serum autoantibodies (7-AABs) at our hospital from January 2020 to April 2024. The univariate and multivariate logistic regression models were performed to screen independent risk factors for benign and malignant pulmonary nodules, based on which a nomogram model was established. The performance of the model was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Results A total of 1 017 patients with pulmonary nodules were included in the study. The training set consisted of 712 patients, including 291 males and 421 females, with a mean age of (58±12) years. The validation set included 305 patients, comprising 129 males and 176 females, with a mean age of (58±13) years. Univariate ROC curve analysis indicated that the combination of CT and 7-AABs testing achieved the highest area under the curve (AUC) value (0.794), surpassing the diagnostic efficacy of CT alone (AUC=0.667) or 7-AABs alone (AUC=0.514). Multivariate logistic regression analysis showed that radiological nodule diameter, nodule nature, and CT combined with 7-AABs detection were independent predictors, which were used to construct a nomogram prediction model. The AUC values for this model were 0.826 and 0.862 in the training and validation sets, respectively, demonstrating excellent performance in DCA. Conclusion The combination of 7-AABs with CT significantly enhances the accuracy of distinguishing between benign and malignant pulmonary nodules. The developed predictive model provides strong support for clinical decision-making and contributes to achieving precise diagnosis and treatment of pulmonary nodules.
4.Principles, technical specifications, and clinical application of lung watershed topography map 2.0: A thoracic surgery expert consensus (2024 version)
Wenzhao ZHONG ; Fan YANG ; Jian HU ; Fengwei TAN ; Xuening YANG ; Qiang PU ; Wei JIANG ; Deping ZHAO ; Hecheng LI ; Xiaolong YAN ; Lijie TAN ; Junqiang FAN ; Guibin QIAO ; Qiang NIE ; Mingqiang KANG ; Weibing WU ; Hao ZHANG ; Zhigang LI ; Zihao CHEN ; Shugeng GAO ; Yilong WU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(02):141-152
With the widespread adoption of low-dose CT screening and the extensive application of high-resolution CT, the detection rate of sub-centimeter lung nodules has significantly increased. How to scientifically manage these nodules while avoiding overtreatment and diagnostic delays has become an important clinical issue. Among them, lung nodules with a consolidation tumor ratio less than 0.25, dominated by ground-glass shadows, are particularly worthy of attention. The therapeutic challenge for this group is how to achieve precise and complete resection of nodules during surgery while maximizing the preservation of the patient's lung function. The "watershed topography map" is a new technology based on big data and artificial intelligence algorithms. This method uses Dicom data from conventional dose CT scans, combined with microscopic (22-24 levels) capillary network anatomical watershed features, to generate high-precision simulated natural segmentation planes of lung sub-segments through specific textures and forms. This technology forms fluorescent watershed boundaries on the lung surface, which highly fit the actual lung anatomical structure. By analyzing the adjacent relationship between the nodule and the watershed boundary, real-time, visually accurate positioning of the nodule can be achieved. This innovative technology provides a new solution for the intraoperative positioning and resection of lung nodules. This consensus was led by four major domestic societies, jointly with expert teams in related fields, oriented to clinical practical needs, referring to domestic and foreign guidelines and consensus, and finally formed after multiple rounds of consultation, discussion, and voting. The main content covers the theoretical basis of the "watershed topography map" technology, indications, operation procedures, surgical planning details, and postoperative evaluation standards, aiming to provide scientific guidance and exploration directions for clinical peers who are currently or plan to carry out lung nodule resection using the fluorescent microscope watershed analysis method.
5.SITA: Predicting site-specific immunogenicity for therapeutic antibodies.
Yewei CUN ; Hao DING ; Tiantian MAO ; Yuan WANG ; Caicui WANG ; Jiajun LI ; Zihao LI ; Mengdie HU ; Zhiwei CAO ; Tianyi QIU
Journal of Pharmaceutical Analysis 2025;15(6):101316-101316
Antibody (Ab) humanization is critical to reduce immunogenicity and enhance efficacy in the preclinical phase of the development of therapeutic Abs originated from animal models. Computational suggestions have long been desired, but available tools focused on immunogenicity calculation of whole Ab sequences and sequence segments, missing the individual residue sites. This study introduces Site-specific Immunogenicity for Therapeutic Antibody (SITA), a novel computational framework that predicts B-cell immunogenicity score for not only the overall antibody, but also individual residues, based on a comprehensive set of amino acid descriptors characterizing physicochemical and spatial features for antibody structures. A transfer-learning-inspired framework was purposely adopted to overcome the scarcity of Ab-Ab structural complexes. On an independent testing dataset derived from 13 Ab-Ab structural complexes, SITA successfully predicted the epitope sites for Ab-Ab structures with a receiver operating characteristic (ROC)-area unver the ROC curve (AUC) of 0.85 and a precision-recall (PR)-AUC of 0.305 at the residue level. Furthermore, the SITA score can significantly distinguish immunogenicity levels of whole human Abs, therapeutic Abs and non-human-derived Abs. More importantly, analysis of an additional 25 therapeutic Abs revealed that over 70% of them were detected with decreased immunogenicity after modification compared to their parent variants. Among these, nearly 66% Abs successfully identified actual modification sites from the top five sites with the highest SITA scores, suggesting the ability of SITA scores for guide the humanization of antibody. Overall, these findings highlight the potential of SITA in optimizing immunogenicity assessments during the process of therapeutic antibody design.
6.Arthroscopic Total Internal Suture Combined With Platelet-rich Plasma for the Treatment of Lateral Meniscal Popliteal Hiatus Area Injuries
Pengfei ZHANG ; Yutong WANG ; Huiwen ZHOU ; Ziheng ZHANG ; Zihao HU ; Yansong QI ; Yongsheng XU
Chinese Journal of Minimally Invasive Surgery 2025;25(8):489-494
Objective To investigate the short-term efficacy of arthroscopic total internal suture combined with platelet-rich plasma(PRP)in the treatment of lateral meniscal popliteal hiatus area injuries.Methods Forty-eight patients diagnosed with lateral meniscal popliteal hiatus area injuries in our hospital from January 2020 to December 2022 were selected and divided into Fast-Fix total internal suture group(FF group,n=23)and Fast-Fix total internal suture combined with PRP group(PRP group,n=25)according to treatment methods.The positive rate of McMurray test at 6 and 12 months after surgery,the preoperative and postoperative visual analogue scale(VAS)of pain,the International Knee Documentation Committee(IKDC)scores,the Lysholm Knee Function Scores,and the Knee Society Scores(KSS)were compared between the two groups.Results No adverse events such as vascular and nerve injury,fever and infection occurred in both groups.There was no significant difference between the two groups in the positive rates of McMurray test at 6 and 12 months(χ2=0.880,P=0.348;Fisher's exact test,P=0.479).In the PRP group,25 cases were followed up for11-14 months,with an average of(12.2±0.8)months;in the FF group,23 cases were followed up for11-14 months,with an average of(12.8±0.8)months.The VAS scores at 6 months and 12 months after surgery were significantly lower than those before surgery in both groups(all P=0.000).The VAS scores of the PRP group at 6 and 12 months after surgery were significantly lower than those of the FF group(P<0.05).Both groups showed significant improvements in IKDC,Lysholm,and KSS scores at 6 and 12 months after surgery compared to preoperative levels(all P=0.000).The IKDC,Lysholm,and KSS scores of the PRP group at 6 and 12 months after surgery were significantly higher than those of the FF group(P<0.05).Conclusion Compared to Fast-Fix total internal suture alone,PRP joint cavity adjuvant therapy based on Fast-Fix total internal suture surgery could reduce the postoperative pain of patients,and promote the functional recovery of the knee joint,which is more recommended in clinical practice.
7.SITA:Predicting site-specific immunogenicity for therapeutic antibodies
Yewei CUN ; Hao DING ; Tiantian MAO ; Yuan WANG ; Caicui WANG ; Jiajun LI ; Zihao LI ; Mengdie HU ; Zhiwei CAO ; Tianyi QIU
Journal of Pharmaceutical Analysis 2025;15(6):1378-1389
Antibody humanization is critical to reduce immunogenicity and enhance efficacy in the preclinical phase of the development of therapeutic antibodies originated from animal models.Computational suggestions have long been desired,but available tools focused on immunogenicity calculation of whole antibody sequences and sequence segments,missing the individual residue sites.This study introduces Site-specific Immunogenicity for Therapeutic Antibody(SITA),a novel computational framework that predicts B-cell immunogenicity score for not only the overall antibody,but also individual residues,based on a comprehensive set of amino acid descriptors characterizing physicochemical and spatial features for antibody structures.A transfer-learning-inspired framework was purposely adopted to overcome the scarcity of Antibody-Antibody structural complexes.On an independent testing dataset derived from 13 Antibody-Antibody structural complexes,SITA successfully predicted the epitope sites for Antibody-Antibody structures with a receiver operating characteristic(ROC)-area unver the ROC curve(AUC)of 0.85 and a precision-recall(PR)-AUC of 0.305 at the residue level.Furthermore,the SITA score can significantly distinguish immunogenicity levels of whole human antibodies,therapeutic antibodies and non-human-derived antibodies.More importantly,analysis of an additional 25 thera-peutic antibodies revealed that over 70%of them were detected with decreased immunogenicity after modification compared to their parent variants.Among these,nearly 66%antibodies successfully iden-tified actual modification sites from the top five sites with the highest SITA scores,suggesting the ability of SITA scores for guide the humanization of antibody.Overall,these findings highlight the potential of SITA in optimizing immunogenicity assessments during the process of therapeutic antibody design.
8.The effect of different types of robotic-assisted therapy on sub-acute stroke patients with mild hemipare-sis of the upper extremity
Zihao WANG ; Chuan HU ; Haiquan ZHANG
Chinese Journal of Rehabilitation Medicine 2025;40(3):397-403
Objective:To compare the rehabilitation effects of exoskeleton(EX)robots and end-effector(EE)robots in patients with mild upper limb hemiparesis in the subacute phase of stroke.Method:From February 2022 to February 2023,30 patients with mild hemiparesis due to stroke were recruit-ed at the Rehabilitation Treatment Center of Shandong University Affiliated Provincial Third Hospital.Using a single-blind design,these patients were randomly assigned to either the EX group or the EE group,with 15 patients in each group.Both groups received robot-assisted therapy in addition to standard rehabilitation treat-ment.The therapy sessions were conducted five days a week for four weeks,with each session lasting 25 min-utes.The affected upper limb was evaluated using the upper extremity Fugl-Meyer assessment(FMA-UE),Wolf motor function test(WMFT),and modified Barthel index(MBI).Assessments were performed at base-line,2 weeks,and 4 weeks.Result:Within-group comparisons revealed that both groups had significant improvements in FMA-UE,WMFT,and MBI scores at the 2-week and 4-week after treatment compared to baseline(P<0.05).However,only the EX group showed continued improvement between 2 and 4 weeks after treatment(P<0.05).Inter-group comparisons demonstrated that the EX group had significantly greater improvement in FMA-UE scores than the EE group at the 4-week assessment(P<0.05),while no significant differences were observed between the two groups for WMFT and MBI scores.Conclusion:The EX robot demonstrated superior upper limb motor function improvement in patients with mild upper limb hemiparesis in subacute phase of stroke.However,no significant differences were observed be-tween the two robots in improving upper limb functional tasks and enhancing independence in activities of dai-ly living.
9.The effect of different types of robotic-assisted therapy on sub-acute stroke patients with mild hemipare-sis of the upper extremity
Zihao WANG ; Chuan HU ; Haiquan ZHANG
Chinese Journal of Rehabilitation Medicine 2025;40(3):397-403
Objective:To compare the rehabilitation effects of exoskeleton(EX)robots and end-effector(EE)robots in patients with mild upper limb hemiparesis in the subacute phase of stroke.Method:From February 2022 to February 2023,30 patients with mild hemiparesis due to stroke were recruit-ed at the Rehabilitation Treatment Center of Shandong University Affiliated Provincial Third Hospital.Using a single-blind design,these patients were randomly assigned to either the EX group or the EE group,with 15 patients in each group.Both groups received robot-assisted therapy in addition to standard rehabilitation treat-ment.The therapy sessions were conducted five days a week for four weeks,with each session lasting 25 min-utes.The affected upper limb was evaluated using the upper extremity Fugl-Meyer assessment(FMA-UE),Wolf motor function test(WMFT),and modified Barthel index(MBI).Assessments were performed at base-line,2 weeks,and 4 weeks.Result:Within-group comparisons revealed that both groups had significant improvements in FMA-UE,WMFT,and MBI scores at the 2-week and 4-week after treatment compared to baseline(P<0.05).However,only the EX group showed continued improvement between 2 and 4 weeks after treatment(P<0.05).Inter-group comparisons demonstrated that the EX group had significantly greater improvement in FMA-UE scores than the EE group at the 4-week assessment(P<0.05),while no significant differences were observed between the two groups for WMFT and MBI scores.Conclusion:The EX robot demonstrated superior upper limb motor function improvement in patients with mild upper limb hemiparesis in subacute phase of stroke.However,no significant differences were observed be-tween the two robots in improving upper limb functional tasks and enhancing independence in activities of dai-ly living.
10.Arthroscopic Total Internal Suture Combined With Platelet-rich Plasma for the Treatment of Lateral Meniscal Popliteal Hiatus Area Injuries
Pengfei ZHANG ; Yutong WANG ; Huiwen ZHOU ; Ziheng ZHANG ; Zihao HU ; Yansong QI ; Yongsheng XU
Chinese Journal of Minimally Invasive Surgery 2025;25(8):489-494
Objective To investigate the short-term efficacy of arthroscopic total internal suture combined with platelet-rich plasma(PRP)in the treatment of lateral meniscal popliteal hiatus area injuries.Methods Forty-eight patients diagnosed with lateral meniscal popliteal hiatus area injuries in our hospital from January 2020 to December 2022 were selected and divided into Fast-Fix total internal suture group(FF group,n=23)and Fast-Fix total internal suture combined with PRP group(PRP group,n=25)according to treatment methods.The positive rate of McMurray test at 6 and 12 months after surgery,the preoperative and postoperative visual analogue scale(VAS)of pain,the International Knee Documentation Committee(IKDC)scores,the Lysholm Knee Function Scores,and the Knee Society Scores(KSS)were compared between the two groups.Results No adverse events such as vascular and nerve injury,fever and infection occurred in both groups.There was no significant difference between the two groups in the positive rates of McMurray test at 6 and 12 months(χ2=0.880,P=0.348;Fisher's exact test,P=0.479).In the PRP group,25 cases were followed up for11-14 months,with an average of(12.2±0.8)months;in the FF group,23 cases were followed up for11-14 months,with an average of(12.8±0.8)months.The VAS scores at 6 months and 12 months after surgery were significantly lower than those before surgery in both groups(all P=0.000).The VAS scores of the PRP group at 6 and 12 months after surgery were significantly lower than those of the FF group(P<0.05).Both groups showed significant improvements in IKDC,Lysholm,and KSS scores at 6 and 12 months after surgery compared to preoperative levels(all P=0.000).The IKDC,Lysholm,and KSS scores of the PRP group at 6 and 12 months after surgery were significantly higher than those of the FF group(P<0.05).Conclusion Compared to Fast-Fix total internal suture alone,PRP joint cavity adjuvant therapy based on Fast-Fix total internal suture surgery could reduce the postoperative pain of patients,and promote the functional recovery of the knee joint,which is more recommended in clinical practice.

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