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Sheng Xu

Sheng Xu

· Professor of Anesthesiology, Perioperative & Pain Medicine (Department Research) and, by courtesy, of Electrical EngineeringVerified

Stanford University · Rheumatology

Active 2000–2025

h-index23
Citations3.9k
Papers9842 last 5y
Funding
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About

Sheng Xu is a Professor of Anesthesiology, Perioperative & Pain Medicine (Department Research) and, by courtesy, of Electrical Engineering at Stanford University. He is affiliated with the Center for Artificial Intelligence in Medicine & Imaging (AIMI). His research focuses on the application of artificial intelligence and imaging techniques in medicine, aiming to advance healthcare through innovative technological solutions. Sheng Xu's work involves integrating AI methodologies with medical imaging to improve diagnostic accuracy and patient outcomes, contributing to the development of intelligent systems in healthcare settings.

Research topics

  • Materials science
  • Nanotechnology
  • Chemical engineering
  • Organic chemistry
  • Chemistry
  • Metallurgy
  • Combinatorial chemistry
  • Polymer chemistry
  • Engineering
  • Biochemistry
  • Medicine
  • Biology
  • Biophysics
  • Nuclear chemistry
  • Geology
  • Inorganic chemistry

Selected publications

  • Unilateral pulmonary vein atresia

    IJTLD OPEN · 2025-04-01

    articleOpen access

    OBJECTIVE: This study aims to summarise the clinical characteristics of unilateral pulmonary vein atresia (UPVA) and compare the differences between Chinese cases and all published cases worldwide. METHODS: We retrospectively enrolled 6 Chinese children with UPVA from January 2014 to January 2024 at a single centre. We reviewed their demographic data, clinical symptoms, laboratory tests, imaging examinations, treatment and prognosis to describe their clinical features. Additionally, the remaining 79 confirmed patients with UPVA, as described in 52 references, were also summarised. RESULTS: UPVA is sporadically distributed worldwide, with the highest number of reported cases in China (27/85) and the United States (20/85). In the overall cohort (85 cases), the patient median age at diagnosis was 5.2 years. The male-to-female ratio was 1:1. Right-sided UPVA was slightly more common, with a right-to-left ratio of 1.4:1. The most frequently reported clinical manifestations were recurrent pneumonia (79.2%), followed by recurrent haemoptysis (48.1%) and exercise intolerance (35.1%). Additionally, 10.4% of patients were asymptomatic. Congenital heart disease was observed in 34.1% of cases, and 20% of patients had comorbid pulmonary hypertension. The overall mortality rate was 8.9%. CONCLUSION: There were no statistically significant differences in the clinical characteristics of UPVA between Chinese patients and all published cases worldwide.

  • Histomorphological development and progression of gastric intramucosal papillary adenocarcinoma—a retrospective study

    Frontiers in Oncology · 2025-12-01

    articleOpen accessCorresponding

    Objective: The aim of this study is to elucidate the developmental process, progression patterns, and histomorphological features of gastric-type intramucosal papillary adenocarcinoma. Methods: This study employed a retrospective research method. Histological examination and immunohistochemical analyses were conducted on endoscopic biopsy samples and endoscopic submucosal dissection (ESD) specimens from 450 cases of superficial gastric epithelial lesions. Results: Atrophic changes in gastric foveolar epithelium, resulting from infectious, chemical, autoimmune, or genetic factors, were associated with a sequential process of tumorigenesis in gastric intramucosal papillary adenocarcinoma. This process involved two phases of compensatory epithelial proliferation followed by three distinct stages of neoplastic transformation. The initial compensatory phase was characterized histologically by papillary hyperplasia of the gastric crypt epithelium. The second phase, representing transitional or dysregulated proliferation, was observed as gastric surface epithelial-type adenoma. The first neoplastic stage was identified as gastric-type low-grade intraepithelial neoplasia, followed by high-grade intraepithelial neoplasia, and culminating in the third stage as gastric-type intramucosal papillary adenocarcinoma. The progression of these stages was delineated based on histopathological features and immunophenotypic profiles. Conclusion: Recognizing the histopathological and immunophenotypic features involved in the stepwise development of gastric-type papillary adenocarcinoma enhances the accuracy of clinical management and surveillance of neoplastic progression. This has significant implications for early intervention and prevention of gastric cancer progression.

  • Biosynthesis, Characterization, and Functional Analysis of Wheat Antifreeze Protein Based on Peptidomics Techniques

    SSRN Electronic Journal · 2025-01-01

    preprintOpen access
  • Abstract 340: GenSci139, a highly differentiated EGFR×HER2 bispecific ADC, for the treatment of multiple solid tumors

    Cancer Research · 2025-04-21 · 1 citations

    articleSenior author

    Abstract Background: Enhertu®/DS-8201, a HER2-directed ADC, has been used for the treatment of multiple tumor types, including HER2-positive and HER2-low breast cancer, HER2-mutant NSCLC, HER2-positive gastric cancer, etc. Despite Enhertu’s success as a breakthrough therapy, significant unmet need remains in the HER2-low settings and in the occurrence of secondary resistance. Dual targeting of EGFR and HER2 represents a promising approach to the treatment of HER2-low patients and to overcoming drug resistance, as they are both oncogenic drivers and widely co-expressed. We developed GenSci139, an EGFR×HER2 bispecific ADC with a highly stable but cleavable linker and a potent topoisomerase 1 inhibitor payload, using our proprietary platform technologies. Preclinical studies are underway to evaluate the potential of GenSci139 as a novel targeted therapy across multiple solid tumor types. Methods: GenSci139’s plasma stability, in vitro cellular binding, internalization, cytotoxicity, and bystander effect, and blocking activity of GenSci139 or its parental bispecific antibody on EGFR/HER2 signaling in a number of human cancer cell lines were characterized. In vivo anti-tumor activity of GenSci139 was evaluated in a number of human cancer CDX models in mice. In addition, the ability of GenSci139 to induce immunogenic cell death (ICD) in tumor cell cultures was assessed. Results: GenSci139 showed much better in vitro plasma stability than DS-8201, suggesting a favorable PK and safety profile. GenSci139 exhibited stronger in vitro tumor cell binding and internalization activities than DS-8201 and potent direct cytotoxicity and bystander killing effect in tumor cell lines. The parental bispecific antibody of GenSci139 inhibited EGF-induced signaling and cell proliferation in tumor cell culture. GenSci139 demonstrated superior in vivo anti-tumor efficacy versus DS-8201 in a number of CDX models in mice. In addition, GenSci139 was shown to induce hallmarks of ICD in tumor cells, providing a complementary anti-tumor mechanism when in a combination therapy regimen with immune checkpoint inhibitors. Conclusion: These data suggest the potential of GenSci139 as a novel and effective therapy across a variety of tumor types, including urothelial cancer, lung cancer, gastric cancer, colorectal cancer, ovarian cancer, breast cancer, etc., and support its further evaluation in IND-enabling studies. Citation Format: Xiaojuan Chai, Fu Li, Hongmei Xie, Yuting Lu, Nan Li, Hanxi Yu, Li Tong, Weiming He, Wenqiang Zhai, Fanglong Yang, John L. Xu. GenSci139, a highly differentiated EGFR×HER2 bispecific ADC, for the treatment of multiple solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 340.

  • Abstract C077: GenSci143, a Novel B7-H3 × PSMA Bispecific Antibody-Drug Conjugate (BsADC), Demonstrates Broad-Spectrum Preclinical Antitumor Efficacy with a Favorable Safety Profile

    Molecular Cancer Therapeutics · 2025-10-22

    article

    Abstract Introduction: B7-H3 (CD276) and prostate-specific membrane antigen (PSMA) are tumor-associated antigens overexpressed in metastatic castration-resistant prostate cancer (mCRPC) and other solid tumors. Clinical limitations of single-target agents include restricted efficacy in mCRPC monotherapy (e.g., DS-7300a [anti-B7-H3 ADC] and ARX517 [anti-PSMA ADC]), often attributed to tumor heterogeneity and variable target expression. To overcome this, we engineered GenSci143, a bispecific ADC (BsADC) targeting both B7-H3 and PSMA, conjugated to a potent TOP1 inhibitor payload. This dual-targeting strategy aims to enhance efficacy and expand treatable patient populations by simultaneously addressing antigen heterogeneity in mCRPC and other solid tumors. Methods: Target expression was evaluated by immunohistochemistry. In vivo efficacy was assessed across multiple cell-derived xenograft (CDX) and patient-derived xenograft (PDX) models representing prostate cancer (PCa), non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and gastric cancer (GC). Combination potential with enzalutamide (endocrine therapy) was evaluated in a PCa PDX model. Biomarkers associated with therapeutic efficacy were analyzed in PCa PDX models. Pharmacokinetic (PK) and toxicology profiles were characterized in cynomolgus monkeys. Results: In PCa CDX/PDX models with varying B7-H3/PSMA expression, GenSci143 exhibited significantly stronger antitumor activity versus benchmark ADCs DS-7300a and ARX517 analogs. Synergy was observed when combining GenSci143 with enzalutamide in a PCa PDX model. GenSci143 also demonstrated potent efficacy in NSCLC and GC CDX/PDX models. A SLFN11-dependent response pattern was observed in PCa PDX models treated with GenSci143 or DS-7300a, but not ARX517, supporting SLFN11 as a biomarker for TOP1 inhibitor response. PK studies revealed favorable drug exposure with linear kinetics. Repeat-dose toxicity assessments in non-human primates indicated a well-tolerated profile. Conclusion: GenSci143, a dual-targeting B7-H3 × PSMA ADC, achieves superior efficacy over DS-7300a and ARX517 analogs in prostate cancer models with heterogeneous target expression, effectively overcoming limitations of single-target ADCs. Its potent activity across multiple solid tumors (NSCLC, GC) and synergy with endocrine therapy support broader clinical applicability. The association with the SLFN11 biomarker may further optimize patient stratification. These results position GenSci143 as a promising therapeutic modality with enhanced efficacy and expanded patient coverage potential for mCRPC and beyond. Citation Format: Liang Xu, Hui Yi. Lin, Xin Chen, Peng Qi, Nan Shao. Liang, Xuan Ye, Yan Li, Qin Yun. Chen, Chun Qu, Yao Xu, Yu Zhi. Cui, Ming Wei. He, Qiang Wen. Zhai, Fu Li, Long Fang. Yang, John L. Xu, Zhen Xiao. Wang, Zhou Hai. Zhang. GenSci143, a Novel B7-H3 × PSMA Bispecific Antibody-Drug Conjugate (BsADC), Demonstrates Broad-Spectrum Preclinical Antitumor Efficacy with a Favorable Safety Profile [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr C077.

  • Prevalence and recurrence rates of spontaneous pneumothorax in patients with diffuse cystic lung diseases in China

    Orphanet Journal of Rare Diseases · 2025-02-11

    articleOpen access

    OBJECTIVES: To investigate the prevalence and recurrence rates of spontaneous pneumothorax (SP) in patients with diffuse cystic lung diseases (DCLDs). METHODS: We retrospectively identified and analyzed medical records of patients with DCLDs encountered at the First Affiliated Hospital of University of Science and Technology of China from Jan 1, 2017 to December 31, 2023. RESULTS: A total of 289 patients were identified with DCLDs; 212 females and 77 males, with a median age of 48 years (range, 18-81 years). Among them, 89 (31%) patients had experienced SP; 59% among 115 patients with Birt-Hogg-Dubé (BHD), 34% of 41 patients with lymphangioleiomyomatosis (LAM, all women), 36% of 11 patients with pulmonary Langerhans cell histiocytosis (PLCH), none of 57 patients with Sjögren's syndrome-associated diffuse cystic lung disease (SS-DCLD), and 5% of 65 patients with no identifiable underlying disease (χ² = 90.585, P < 0.001). The overall recurrence rate of SP was higher with observation or chest tube placement strategy compared to surgical intervention, 59% vs. 11% (P < 0.001, 95% CI [0.1, -0.4]), respectively. The recurrence rate after surgical management was significantly lower compared to conservative management in patients with BHD (10% vs. 69%, P < 0.001, 95% CI [0.1, 0.3]) and LAM (20% vs. 57%, P = 0.322, 95% CI [0.1, 2.1]). Among patients with BHD, LAM, and PLCH, those who had pneumothorax as the initial presentation were diagnosed of their underlying disease at a significantly younger age (42.2 ± 13.0 years) compared to those without pneumothorax (48.1 ± 11.8 years) (P = 0.032, 95% CI [-8.24, -0.36]). Notably, eight of LAM patients who were treated with sirolimus after the initial SP did not experience recurrence of SP. CONCLUSION: The risk of SP secondary to DCLDs was highest in patients with BHD, followed by those with PLCH and LAM. It was extremely low in SS-DCLD. Pneumothorax as the initial presentation often facilitated diagnosis of the underlying disease. Surgical treatment was associated with a lower recurrence rate of SP compared to nonsurgical management. In addition, sirolimus therapy may reduce the risk of pneumothorax recurrence in patients with LAM.

  • Abstract A135: GS24-B057, a potential best-in-class Nectin-4- and Trop-2-directed bispecific ADC, for the treatment of multiple solid tumors

    Molecular Cancer Therapeutics · 2025-10-22 · 1 citations

    articleSenior author

    Abstract Background: Nectin-4 and Trop-2 are transmembrane proteins commonly co-overexpressed in various solid tumors and associated with tumor progression. ADCs targeting Nectin-4 or Trop-2 have shown promising therapeutic potential in urothelial carcinoma (UC), non-small cell lung cancer (NSCLC), and triple-negative breast cancer (TNBC). Notably, the combination of Padcev™ (a Nectin-4-directed ADC; also referred to as EV) and Trodelvy™ (a Trop-2-directed ADC; also referred to as SG) as second-line therapy for metastatic UC has demonstrated significantly improved efficacy, with the overall response rate (ORR) reaching 70%. However, the safety profile of this combination remains to be a concern, with ≥Grade 3 treatment-emergent adverse events (TEAEs) occurring in 78% of patients. To enhance clinical efficacy while minimizing toxicity, we developed GS24-B057, a dual Nectin-4- and Trop-2-targeting ADC with a drug-to-antibody ration (DAR) of 6, integrating an optimally engineered bispecific antibody, a tailored topoisomerase I inhibitor payload, and site-specific conjugation. Materials and Methods: The in vitro tumor cell binding and internalization activity of GS24-B057 were evaluated by flow cytometry in Nectin-4 and Trop-2 positive cell lines. Cytotoxicity and bystander killing effect were assessed in a Cell Titer-Glo assay and in a luciferase assay, respectively. The in vivo anti-tumor efficacy of GS24-B057 was systematically examined in a number of human cancer cell line-derived xenograft (CDX) models in mice. Results: In preclinical studies, GS24-B057 exhibited significantly stronger in vitro cell binding and internalization than EV and SG, as well as robust direct cytotoxicity and pronounced bystander killing effect in tumor cell lines. GS24-B057 demonstrated superior in vivo anti-tumor efficacy as compared to the EV and SG combination in a number of CDX models including UC and TNBC. A pilot non-GLP 4-week repeat dose toxicity study in cynomolgus monkeys has been planned. Conclusion: These data suggest the potential of GS24-B057 as an effective therapeutic option for patients with UC and TNBC and support its further evaluation in IND-enabling studies. Citation Format: Meihan Li, Fu Li, Qiuru Che, Dongxia Chu, Qiyang Zhang, Xiaojing Huang, Nan Li, Qingjuan Ma, Shaonan Liang, Weiming He, Yihui Lin, Wenqiang Zhai, Fanglong Yang, Siqing Wang, Lei Jin, John L. Xu. GS24-B057, a potential best-in-class Nectin-4- and Trop-2-directed bispecific ADC, for the treatment of multiple solid tumors [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr A135.

  • Controlled distribution of both Pt nanoparticles and ionomer in self-supported nanoporous carbon scaffolds significantly enhances oxygen reduction kinetics and stability

    Journal of Materials Chemistry A · 2025-01-01 · 3 citations

    articleOpen access

    Keeping Pt NPs and Nafion in their own microenvironments in a PEM fuel cell cathode catalyst layer results in exceptional ORR kinetics and stability.

  • Helicobacter pylori VacA-induced gastric mucosal atrophy: a comparative analysis with other forms of atrophic gastritis

    Journal of Molecular Histology · 2025-06-01

    articleSenior author
  • Mechanism of Helicobacter pylori vacuolar cytotoxin a-induced gastric mucosal atrophy: A histopathological and immunohistochemical analysis

    Diagnostic Microbiology and Infectious Disease · 2025-03-07

    articleSenior authorCorresponding

Frequent coauthors

  • Fritz B. Prinz

    33 shared
  • Yufan Lian

    Third Affiliated Hospital of Sun Yat-sen University

    16 shared
  • Lei Tan

    Guangzhou Center for Disease Control and Prevention

    16 shared
  • Jie Ren

    Sun Yat-sen University

    16 shared
  • Bowen Zheng

    Nanfang Hospital

    16 shared
  • Tao Wu

    Third Affiliated Hospital of Sun Yat-sen University

    16 shared
  • Tinghui Yin

    Third Affiliated Hospital of Sun Yat-sen University

    12 shared
  • Thomas F. Jaramillo

    11 shared
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