1.Effect of different liver biopsy needle track management on Yttrium-90 selective internal radiation therapy on liver cancer
Zhenyuan XU ; Xue LIU ; Shuqun SHEN ; Zhijia XU ; Changkai LI ; Yefa YANG
Chinese Journal of Clinical Medicine 2025;32(2):288-294
Objective To explore the effect of different needle track management on Yttrium-90 microsphere selective internal radiation therapy (90Y-SIRT) on liver cancer after liver biopsy. Methods A retrospective analysis was conducted on the clinical data of 21 patients with liver cancer who underwent Technetium-99m-macroaggregated albumin (99mTc-MAA) evaluation and 90Y-SIRT after liver biopsy from June 2023 to December 2024. The methods of needle track management, hepatic arteriovenous shunting, and lung shunt fraction (LSF) were recorded. The occurrence of hepatic arteriovenous fistula (HAVF), as well as the corresponding countermeasures were analyzed. Results Among the 21 liver cancer patients, 7 cases (medical glue group) underwent embolization of the needle tract with medical glue (N-butyl 2-cyanoacrylate [NBCA]) immediately after biopsy, and no significant HAVF was observed during the 99mTc-MAA tests; 14 cases (non-medical glue group) were treated with delayed needle extraction or gelatin sponge particle blocking after biopsy, among which 7 cases developed significant HAVF, and the fistulas were treated with NBCA. The LSF of the medical glue group was significantly lower than that of the non-medical glue group ([7.06±2.33] % vs [12.43±7.73] %, P=0.037). All 21 patients successfully completed 90Y-SIRT. Conclusions Liver biopsy may affect 90Y-SIRT by causing iatrogenic HAVF. Immediate NBCA-embolization of the needle tract after biopsy or timely NBCA-embolization of fistulas during 99mTc-MAA tests may reduce the impact.
2.Chemical knockdown of Keap1 and homoPROTAC-ing allergic rhinitis.
Jianyu YAN ; Tianyu WANG ; Ruizhi YU ; Lijuan XU ; Hongming SHAO ; Tengfei LI ; Zhe WANG ; Xudong CHA ; Zhenyuan MIAO ; Chengguo XING ; Ke XU ; Huanhai LIU ; Chunlin ZHUANG
Acta Pharmaceutica Sinica B 2025;15(8):4137-4155
Allergic rhinitis (AR), a globally prevalent immune-mediated inflammatory condition, is still an incurable disease. In the present study, we have validated the impact of the Kelch-like ECH associated protein 1 (Keap1)-related oxidative stress and inflammatory response in clinical AR patient peripheral blood and nasal swab samples, emphasizing the biological relevance of Keap1 and AR. Targeting Keap1 -nuclear factor erythroid 2-related factor 2 (Nrf2) related anti-oxidative stress may be effective for AR intervention. Drawing inspiration from the Keap1 homodimerization and the E3 ligase characteristics, we herein present a design of novel bivalent molecules for chemical knockdown of Keap1. For the first time, we characterized ternary complexes of Keap1 dimer and one molecule of bivalent compounds. The best bivalent molecule 8 encompasses robust capacity to degrade Keap1 as a homoPROTACKEAP1. It efficaciously suppresses inflammatory cytokines in extensively different cells, including human nasal epithelial cells. Moreover, in an AR mouse model, we confirmed that the chemical degradation induced by homoPROTACKEAP1 led to therapeutic benefits in managing AR symptoms, oxidative stress and inflammation. In summary, our findings underscore the efficacy of targeting the Keap1 system through the homoPROTAC-ing technology as an innovative and promising treatment strategy for the incurable allergic disorders.
3.Research progress and prospects of artificial intelligence in diagnosis and treatment of colorectal cancer
Wei WEI ; Kunshan HE ; Zhenyuan HU ; Zhenyu LIU ; Jianqiang TANG ; Jie TIAN
Chinese Journal of Gastrointestinal Surgery 2024;27(1):15-23
Colorectal cancer is one of the most common malignant tumors worldwide. Due to the heterogeneity in patient outcomes and treatment responses to standard therapy regimens, personalized diagnostic and therapeutic strategies have remained a focus of sustained interest in research. In recent years, with the rapid progression of artificial intelligence (AI) technology in the medical field, an abundance of phased research results has emerged in the decision-making for preoperative, intraoperative, and postoperative diagnostic and therapeutic plans for colorectal cancer, demonstrating great potential for application. This new and efficient solution provides for the personalized evaluations and auxiliary diagnoses and treatments of patients with colorectal cancer. In the future, AI systems may continue to advance towards multimodal, multi-omics, and real-time directions. This paper aims to explore the current state of research on the multi-faceted auxiliary applications of AI in the diagnosis and treatment of colorectal cancer, as well as to present a prospective view of the innovations that AI technology could bring to personalized colorectal cancer treatment in the future and the challenges it may face.
4.Research progress and prospects of artificial intelligence in diagnosis and treatment of colorectal cancer
Wei WEI ; Kunshan HE ; Zhenyuan HU ; Zhenyu LIU ; Jianqiang TANG ; Jie TIAN
Chinese Journal of Gastrointestinal Surgery 2024;27(1):15-23
Colorectal cancer is one of the most common malignant tumors worldwide. Due to the heterogeneity in patient outcomes and treatment responses to standard therapy regimens, personalized diagnostic and therapeutic strategies have remained a focus of sustained interest in research. In recent years, with the rapid progression of artificial intelligence (AI) technology in the medical field, an abundance of phased research results has emerged in the decision-making for preoperative, intraoperative, and postoperative diagnostic and therapeutic plans for colorectal cancer, demonstrating great potential for application. This new and efficient solution provides for the personalized evaluations and auxiliary diagnoses and treatments of patients with colorectal cancer. In the future, AI systems may continue to advance towards multimodal, multi-omics, and real-time directions. This paper aims to explore the current state of research on the multi-faceted auxiliary applications of AI in the diagnosis and treatment of colorectal cancer, as well as to present a prospective view of the innovations that AI technology could bring to personalized colorectal cancer treatment in the future and the challenges it may face.
5.Study on quality improvement in organisational structure and management model of integrated community child health services
Yaoyuan ZHANG ; Yili DAI ; Tianyu WANG ; Zhenyuan SHEN ; Hongmei HUAN ; Fulai SHEN ; Yu FENG ; Jiaoyu LIU
Chinese Journal of General Practitioners 2024;23(12):1270-1275
Objective:To explore the quality improvement in the organization structure and management model of the integrated community child health services.Methods:This was a qualitative study, including two parts: cause analysis and service improvement suggestions. In the analysis part the data mining was conducted to identify valuable patterns and relationships in the comprehensive child health services. Semi-structured interviews were conducted with 12 relevant department heads and health workers of the comprehensive child health service team at Gumei Community Health Service Center in December 2023, and the causes of the key problems were explored. In the service improvement part, focus group discussions were held to propose suggestions, then improvement measures were formulated to address the identified problems.Results:Through data mining and semi-structured interviews, the key problems were identified: information isolation among multiple departments and lack of coordination mechanism in the comprehensive child health service team. A team organizational structure based on the "three definite" principle was established. The organizational structure should include the pediatric family doctor team, general practitioner management team and departments of pediatrics, maternal and child health care, immunization and child rehabilitation; the management model should include a cross-department resource and information sharing mechanism, the pediatric family doctor model, optimization and integration of physical space, and enhancement of publicity activities for the comprehensive child health services.Conclusion:Based on the analysis in Gumei health service center, this study identified key problems in community integrated child health services, and proposes the quality improvement measure in the organizational structure and management model of the service team.
6.Assessment of the clinical effect of aortic endovascular remodeling device (AERD) for type A aortic dissection
Zhenyuan XU ; Haiyue WANG ; Chen LU ; Yu LIU ; Peng YANG ; Hongwei ZHANG ; Zhenghua XIXO ; Wei MENG ; Jia HU
Chinese Journal of Thoracic and Cardiovascular Surgery 2024;40(6):324-330
Objective:To investigate the early and mid-term outcomes of aortic endovascular remodeling device (AERD) for Stanford type A aortic dissection (TAAD) in type Ⅱhybrid surgery, and to evaluate its clinical efficacy.Methods:46 patients with TAAD, including 14 females and 32 males, participated in the single-center clinical trial of West China Hospital of Sichuan University and underwent type II hybrid surgery (Bentall / ascending aorta replacement + AERD implantation) from February 2021 to October 2023. The safety and efficacy of AERD in type Ⅱ hybrid surgery for TAAD were estimated by clinical indicators (postoperative mortality, cardiovascular and cerebrovascular accidents, paraplegia, ischemia), and blood flow condition (volume of the true and false lumen, and suprachial branches).Results:Three patients (6.52%) died during the follow-up period, and the operation-related mortality was 4.35% (2/46). The remaining 43 patients were followed up for an average of (25.53±9.60) months. There were two cases (4.35%) of stroke after the operation, and paraplegia, acute renal insufficiency, and other severe complications were not noticed. The blood flow of the superior branch of the aortic arch was unobstructed, and there was no significant difference in the blood flow of the branch before the operation and at each follow-up time point. Compared to the pre-operation, the true lumen volume of the stent part increased by 59.0% and the false lumen volume decreased by 82.4%.Conclusion:AERD is a safe and effective alternative in type II hybrid surgery for acute TAAD, which is helpful in improving perioperative and short- and long-term survival rates and clinical outcomes.
7.Knockdown of nuclear protein 1 delays pathological pro-gression of osteoarthritis through inhibiting chondrocyte ferroptosis.
Taiyang LIAO ; Zhenyuan MA ; Deren LIU ; Lei SHI ; Jun MAO ; Peimin WANG ; Liang DING
Journal of Zhejiang University. Medical sciences 2024;53(6):669-679
OBJECTIVES:
To investigate the effect of nuclear protein (Nupr) 1 on the pathological progression of osteoarthritis and its relationship with ferroptosis of chondrocytes.
METHODS:
Chondrocytes from mouse knees were divided into small interfering RNA (siRNA) control group, small interfering RNA targeting Nupr1 (siNupr1) group, siRNA control+IL-1β group (siRNA control interference for 24 h followed by 10 ng/mL IL-1β) and siNupr1+IL-1β group (siNupr1 interference for 24 h followed by 10 ng/mL IL-1β). The protein and mRNA expressions of Nupr1 were detected by Western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Cell proliferation viabilities were measured using the cell counting kit-8 method. The levels of ferrous ions were detected by FerroOrange staining. Lipid peroxidation levels were detected by C11-BODIPY-591 fluorescence imaging. The contents of malondialdehyde (MDA) and glutathione (GSH) were detected by enzyme-linked immunosorbent assay. The protein expressions of acyl-CoA synthetase long-chain family (ACSL) 4, P53, glutathione peroxidase (GPX) 4 and solute carrier family 7 member 11 gene (SLC7A11) were detected by Western blotting. The osteoarthritis model was constructed by destabilization of the medial meniscus (DMM) surgery in 7-week-old male C57BL/6J mice. The mice were randomly divided into four groups with 10 animals in each group: sham surgery (Sham)+adeno-associated virus serotype 5 (AAV5)-short hairpin RNA (shRNA) control group, Sham+AAV5-shRNA control targeting Nupr1 (shNupr1) group, DMM+AAV5-shRNA control group, and DMM+AAV5-shNupr1 group. Hematoxylin and eosin staining and Safranin O-Fast Green staining were used to observe the morphological changes in cartilage tissue. The Osteoarthritis Research Society International (OARSI) osteoarthritis cartilage histopathology assessment system was used to evaluate the degree of cartilage degeneration in mice. The mRNA expressions of matrix metallopeptidase (MMP) 13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 5, cyclooxy-genase (COX) 2, and GPX4 were detected by qRT-PCR.
RESULTS:
In vitro experiments showed that knocking down Nupr1 alleviated the decrease of chondrocyte proliferation activity induced by IL-1β, reduced iron accumulation in mouse chondrocytes, lowered lipid peroxidation, downregulated ACSL4 and P53 protein expression and upregulated GPX4 and SLC7A11 protein expression (all P<0.01), thereby inhibiting ferroptosis in mouse chondrocytes. Meanwhile, in vivo animal experiments demonstrated that knocking down Nupr1 delayed the degeneration of articular cartilage in osteoarthritis mice, improved the OARSI score, slowed down the degradation of the extracellular matrix in osteoarthritis cartilage, and reduced the expression of the key ferroptosis regulator GPX4 (all P<0.01).
CONCLUSIONS
Knockdown of Nupr1 can delay the pathological progression of osteoarthritis through inhibiting ferroptosis in mouse chondrocytes.
Animals
;
Ferroptosis
;
Mice
;
Chondrocytes/metabolism*
;
Osteoarthritis/pathology*
;
RNA, Small Interfering/genetics*
;
Basic Helix-Loop-Helix Transcription Factors/genetics*
;
Interleukin-1beta/metabolism*
;
Phospholipid Hydroperoxide Glutathione Peroxidase/genetics*
;
Coenzyme A Ligases/genetics*
;
Tumor Suppressor Protein p53/metabolism*
;
Mice, Inbred C57BL
;
DNA-Binding Proteins
;
Neoplasm Proteins
;
Amino Acid Transport System y+
;
Nuclear Receptor Subfamily 1, Group D, Member 1
8.Advances in the Immunotherapeutic Potential of Isocitrate Dehydrogenase Mutations in Glioma.
Feng TANG ; Zhiyong PAN ; Yi WANG ; Tian LAN ; Mengyue WANG ; Fengping LI ; Wei QUAN ; Zhenyuan LIU ; Zefen WANG ; Zhiqiang LI
Neuroscience Bulletin 2022;38(9):1069-1084
Isocitrate dehydrogenase (IDH) is an essential metabolic enzyme in the tricarboxylic acid cycle (TAC). The high mutation frequency of the IDH gene plays a complicated role in gliomas. In addition to affecting gliomas directly, mutations in IDH can also alter their immune microenvironment and can change immune-cell function in direct and indirect ways. IDH mutations mediate immune-cell infiltration and function by modulating immune-checkpoint gene expression and chemokine secretion. In addition, IDH mutation-derived D2-hydroxyglutarate can be absorbed by surrounding immune cells, also affecting their functioning. In this review, we summarize current knowledge about the effects of IDH mutations as well as other gene mutations on the immune microenvironment of gliomas. We also describe recent preclinical and clinical data related to IDH-mutant inhibitors for the treatment of gliomas. Finally, we discuss different types of immunotherapy and the immunotherapeutic potential of IDH mutations in gliomas.
Brain Neoplasms/therapy*
;
Glioma/therapy*
;
Humans
;
Immunotherapy
;
Isocitrate Dehydrogenase/genetics*
;
Mutation/genetics*
;
Tumor Microenvironment
9.The correlation between inflammation levels and lung function on patients defined by different TCM syndromes with acute exacerbation of chronic obstructive pulmonary disease
Rui WEI ; Lina YOU ; Jie XIA ; Li LEI ; Chaoyuan LIU ; Zhenyuan WU ; Xia PAN
International Journal of Traditional Chinese Medicine 2020;42(5):421-426
Objective:To observe the changes of neutrophil to lymphocyte ratio and lung function of patients defined by different TCM syndromes with acute exacerbation of chronic obstructive pulmonary disease.Methods:A total of 181 patients with acute exacerbation of chronic obstructive pulmonary disease in our hospital from January 2016 to Novenber 2018 were included and divided into 5 groups accoding to different TCM syndromes, which were wind-cold invading lung syndrome (26), external cold and internal fluid syndrome (40), phlegm-heat obstructing lung syndrome (48), phlegm-dampness blocked syndrome (48), an heart spirit confused by phlegm syndrome (19). Then tested the blood for each group, and calculated NLR; tested c-reactive protein, and lung function, and measured with COPD Assessment Test (CAT) and Modified British Medical Research Council (mMRC); conducted 6MWT, then the BODE index and Charlson Comorbidity Index (CCI) scores were calculated.Results:The NLR, CRP level in patients with external cold and internal fluid syndrome and an heart spirit confused by phlegm syndromeby phlegm were significantly higher than those of other syndrome ( P<0.05 or P<0.01), and FEV1% Pred was significantly lower than that of phlegm-dampness blocked syndrome ( P=0.024); the 6-minute walking distance of patients with external cold and internal fluid syndrome was significantly shorter than that of phlegm-heat obstructing lung syndrome and phlegm-dampness blocked syndrome ( P=0.006, P=0.024). The comparison of mMRC grades among the syndromes was statistically significant ( F=26.367, P=0.049). The BODE index of patients external cold and internal fluid syndrome was higher than that of patients phlegm-heat obstructing lung syndrome ( P=0.015), and the CCI score of patients an heart spirit confused by phlegm syndrome was higher than that of patients phlegm-dampness blocked syndrome ( P=0.012). The BODE index of patients with external cold internal fluid syndrome was significantly higher than that of phlegm-heat obstructing lung syndrome ( P=0.015). The CCI score of patients with mental disorder caused by phlegm was significantly higher than that of phlegm-dampness blocked lung syndrome ( P=0.012). Conclusions:There were significantly differences in neutrophil to lymphocyte ratio, CRP and 6-minute walking distance among different TCM syndromes in patients with acute exacerbation of chronic obstructive pulmonary disease. The inflammation in patients with external cold and internal fluid syndrome and mental disorder caused by phlegmare much severe, but there might be no difference in dyspnea and prognosis among TCM syndromes.
10.Wristband pedometer-measured activity and its determinants among middle school students
YU Dandan, NIE Lianlian, YANG Zhenyuan, ZHANG Lingling, LIU Xiaowei
Chinese Journal of School Health 2019;40(10):1475-1477
Objective:
To improve physical activity by assessing pedometer-based physical activity during specific intervals over a week, among junior high school students,and to provide a reference for improving the level of students’ physical activity.
Methods:
Students (n=675) of grades 6-8 from six public junior high schools in Shanghai were recruited and instructed to wear a pedometer for a week, step counts and contents were recorded over a specific period. This period mainly included steps taken on the way to and from school, at school, at home in the evening on weekdays, and in the morning, afternoon, and evening on weekends.
Results:
The daily step counts recorded were 8 332 steps, with those on weekdays showing significantly higher values than step counts on weekends (9 065 steps vs. 6 392 steps)(t=22.9, P<0.01). Proportionately, the physical activity level at school contributed more to daily step counts (61.3%), followed by those on the commute to and from school(25.5%). Boys were more active than girls. For all intervals on weekdays, the step counts of students in rural districts, with overweight or obese, in grades 6 and 7, were higher than those in urban districts, with normal status, in grade 8 respectively (P<0.05). Low-activity students with physical education were more active than one without physical education(t boy=1.99,t girl=2.45,P<0.05).
Conclusion
These findings facilitate the implementation of effective, feasible interventions to enhance physical activity over a series of intervals during the day.


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