1.Whole genome sequence characteristics of 13 dengue virus serotype 2 strains isolated from Guangzhou in 2023
MA Jinzhe ; LIANG Yufeng ; ZHOU Zhijian
China Tropical Medicine 2025;25(1):110-
Objective To analyze the whole genome sequence characteristics of dengue serotype 2 virus (DENV-2) strains isolated from Guangzhou in 2023, providing new foundational data to support local dengue fever prevention and control efforts. Methods Dengue viruses were isolated from serum samples of dengue fever patients using C6/36 cells. Whole genome sequencing of dengue virus was performed using Nanopore sequencing technology (Nanopore platform). The sequencing data were assembled utilizing IPH-NANO v1.0 software, and homology analysis, phylogenetic analysis, and amino acid site variation analysis of the dengue virus genome sequence were conducted using software such as BioEdit7.0.9.0, MEGA11, and iqTree1.6.12. Results A total of 13 DENV-2 isolates were obtained from the serum samples of dengue fever patients in Guangzhou in 2023, all of which were derived from locally infected cases. The whole genome sequences obtained by sequencing and splicing ranged from 10 429-10 439 nt in length. The nucleotide (amino acid) homology among the 13 isolates was 99.7%-99.9% (99.6%-9.9%). A genome-wide phylogenetic analysis showed that the genotypes of all 13 Guangzhou isolates were identified as the Cosmopolitan genotype and were grouped in the same evolutionary clade as isolates from Réunion (French overseas territory), Djibouti, Kenya, and other regions. Compared with the reference sequence (NC001474), a total of 26 amino acid site variations were identified in the C/prM/E protein regions of the 13 isolates, including 4 variations in the C protein region, 8 in the prM protein region, and 14 in the E protein region. Conclusion The DENV-2 strains isolated from Guangzhou in 2023 exhibited high homology, with closely related isolates primarily originating from countries or regions such as Réunion, Djibouti, and Kenya, it highlights the need for further assessment of the risk of dengue fever importation from East Africa, South Asia, and other regions.
2.Computational pathology in precision oncology: Evolution from task-specific models to foundation models.
Yuhao WANG ; Yunjie GU ; Xueyuan ZHANG ; Baizhi WANG ; Rundong WANG ; Xiaolong LI ; Yudong LIU ; Fengmei QU ; Fei REN ; Rui YAN ; S Kevin ZHOU
Chinese Medical Journal 2025;138(22):2868-2878
With the rapid development of artificial intelligence, computational pathology has been seamlessly integrated into the entire clinical workflow, which encompasses diagnosis, treatment, prognosis, and biomarker discovery. This integration has significantly enhanced clinical accuracy and efficiency while reducing the workload for clinicians. Traditionally, research in this field has depended on the collection and labeling of large datasets for specific tasks, followed by the development of task-specific computational pathology models. However, this approach is labor intensive and does not scale efficiently for open-set identification or rare diseases. Given the diversity of clinical tasks, training individual models from scratch to address the whole spectrum of clinical tasks in the pathology workflow is impractical, which highlights the urgent need to transition from task-specific models to foundation models (FMs). In recent years, pathological FMs have proliferated. These FMs can be classified into three categories, namely, pathology image FMs, pathology image-text FMs, and pathology image-gene FMs, each of which results in distinct functionalities and application scenarios. This review provides an overview of the latest research advancements in pathological FMs, with a particular emphasis on their applications in oncology. The key challenges and opportunities presented by pathological FMs in precision oncology are also explored.
Humans
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Precision Medicine/methods*
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Medical Oncology/methods*
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Artificial Intelligence
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Neoplasms/pathology*
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Computational Biology/methods*
3.Food-derived bioactive peptides: health benefits, structure‒activity relationships, and translational prospects.
Hongda CHEN ; Jiabei SUN ; Haolie FANG ; Yuanyuan LIN ; Han WU ; Dongqiang LIN ; Zhijian YANG ; Quan ZHOU ; Bingxiang ZHAO ; Tianhua ZHOU ; Jianping WU ; Shanshan LI ; Xiangrui LIU
Journal of Zhejiang University. Science. B 2025;26(11):1037-1058
Food-derived bioactive peptides (FBPs), particularly those with ten or fewer amino acid residues and a molecular weight below 1300 Da, have gained increasing attention for their safe, diverse structures and specific biological activities. The development of FBP-based functional foods and potential medications depends on understanding their structure‒activity relationships (SARs), stability, and bioavailability properties. In this review, we provide an in-depth overview of the roles of FBPs in treating various diseases, including Alzheimer's disease, hypertension, type 2 diabetes mellitus, liver diseases, and inflammatory bowel diseases, based on the literature from July 2017 to Mar. 2023. Subsequently, attention is directed toward elucidating the associations between the bioactivities and structural characteristics (e.g., molecular weight and the presence of specific amino acids within sequences and compositions) of FBPs. We also discuss in silico approaches for FBP screening and their limitations. Finally, we summarize recent advancements in formulation techniques to improve the bioavailability of FBPs in the food industry, thereby contributing to healthcare applications.
Humans
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Peptides/therapeutic use*
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Structure-Activity Relationship
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Functional Food
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Diabetes Mellitus, Type 2/drug therapy*
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Biological Availability
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Alzheimer Disease/drug therapy*
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Inflammatory Bowel Diseases/drug therapy*
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Hypertension/drug therapy*
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Liver Diseases/drug therapy*
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Bioactive Peptides, Dietary
4.Mid to long-term clinical outcomes improvement through dual antiplatelet therapy after coronary artery bypass grafting: Interpretation of DACAB-FE trial
Jianyu QU ; Si CHEN ; Zhijian WANG ; Kang ZHOU ; Yuan ZHAO ; Ran DONG ; Dongmei SHI ; Nianguo DONG ; Zhe ZHENG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(08):1096-1100
Coronary artery bypass grafting (CABG) is one of the most effective revascularization treatments for coronary heart disease. Secondary prevention strategies, which rely on antiplatelet and lipid-lowering drugs, are crucial after CABG to ensure the durability of revascularization treatment effects and prevent adverse cardiovascular and cerebrovascular events in the medium to long term. Previous research conducted by Professor Zhao Qiang's team from Ruijin Hospital of Shanghai Jiao Tong University, known as the DACAB study, indicated that dual antiplatelet therapy (DAPT, specifically ticagrelor+aspirin) after CABG can enhance venous graft patency. However, it remains uncertain whether DAPT can further improve the medium to long-term clinical outcomes of CABG patients. Recently, the team reported the medium to long-term follow-up results of the DACAB study, termed the DACAB-FE study, finding that DAPT administered after CABG can reduce the incidence of major cardiovascular events over five years and improve patients' medium to long-term clinical outcomes. This article will interpret the methodological highlights and significant clinical implications of the DACAB-FE study.
5.Practiceand exploration of the reform of super-department system under the guidance of party building to promote high-quality development of hospital
Zijun HUANG ; Yajie LV ; Xueqiong LUO ; Kai ZHOU ; Chunzi LI ; Zhijian GUO
Modern Hospital 2024;24(1):3-6
Establishing a governance structure and an operational model that is compatible with modern hospital manage-ment systems,deepening the reform of hospital management institutions,and exploring the implementation of Super-department System with unified functions are inevitable requirements for promoting the high-quality development of public hospitals.Hospital of Stomatology of Sun Yat-sen University takes the Xi Jinping Thought on Socialism with Chinese Characteristics for a New Era as a guide and fully implements the"Opinions of the General Office of the State Council on Promoting the High Quality Development of Public Hospitals,"integrates party building work and vocational work,carries out practical exploration of the reform of the Su-per-department System,and leads the hospital to achieve phased results in high-quality development.
6.Application of automatic slide-dropping instrument in bone marrow chromosomal karyotyping
Wei ZHANG ; Chenghua CUI ; Ji ZHOU ; Yanyi LYU ; Siping WANG ; Shenghua CHEN ; Huijun WANG ; Qi SUN ; Zhijian XIAO ; Chengwen LI
Chinese Journal of Medical Genetics 2024;41(7):803-806
Objective:To explore the application of an automatic slide-dropping instrument in bone marrow chromosomal karyotyping.Methods:The effects of manual and automatic dropping methods under different environmental humidity were retrospectively analyzed, and the repeatability of the automatic dropping method was analyzed.Results:No statistical difference was found between the results of automatic and manual dropping methods under the optimum ambient humidity and high humidity ( P>0.05). At low humidity, there was a statistical difference between the two methods ( P<0.05). With regard to the repeatability, the coefficient of variations of the automatic dropping method for the number of split phases, the rate of good dispersion and the rate of overlap were all lower than those of the manual dropping method. A statistical difference was also found in the number of split phases ( P<0.05) but not in the discrete excellent rate and overlapping rate between the two methods ( P>0.05). Conclusion:Better effect can be obtained by the automatic dropping instrument. It is suggested to gradually replace manual work with machine.
7.Targeting NUF2 suppresses gastric cancer progression through G2/M phase arrest and apoptosis induction
Bo LONG ; Huinian ZHOU ; Lixia XIAO ; Xiangyan JIANG ; Jian LI ; Zhijian MA ; Na HE ; Wei XIN ; Boya ZHANG ; Xiaoqin ZHU ; Zeyuan YU ; Zuoyi JIAO
Chinese Medical Journal 2024;137(20):2437-2451
Background::Gastric cancer (GC), a malignant tumor with poor prognosis, is one of the leading causes of cancer-related deaths worldwide; consequently, identifying novel therapeutic targets is crucial for its corresponding treatment. NUF2, a component of the NDC80 kinetochore complex, promotes cancer progression in multiple malignancies. Therefore, this study aimed to explore the potential of NUF2 as a therapeutic target to inhibit GC progression. Methods::Clinical samples were obtained from patients who underwent radical resection of GC at Lanzhou University Second Hospital from 2016 to 2021. Cell count assays, colony formation assays, and cell-derived xenotransplantation (CDX) models were used to determine the effects of NUF2 on GC progression. Flow cytometry was used to detect the effect of NUF2 or quercetin on cell cycle progression and apoptosis. A live-cell time-lapse imaging assay was performed to determine the effect of NUF2 on the regulation of mitotic progression. Transcriptomics was used to investigate the NUF2-associated molecular mechanisms. Virtual docking and microscale thermophoresis were used to identify NUF2 inhibitors. Finally, CDX, organoid, and patient-derived xenograft (PDX) models were used to examine the efficacy of the NUF2 inhibitor in GC. Results::NUF2 expression was significantly increased in GC and was negatively correlated with prognosis. The deletion of NUF2 suppressed GC progression both in vivo and in vitro. NUF2 significantly regulated the mitogen-activated protein kinase (MAPK) pathway, promoted G2/M phase transition, and inhibited apoptosis in GC cells. Additionally, quercetin was identified as a selective NUF2 inhibitor with low toxicity that significantly suppressed tumor growth in GC cells, organoids, CDX, and PDX models. Conclusions::Collectively, NUF2-mediated G2/M phase transition and apoptosis inhibition promoted GC progression; additionally, NUF2 inhibitors exhibited potent anti-GC activity. This study provides a new strategy for targeting NUF2 to suppress GC progression in clinical settings.
8.Application of gecacitinib hydrochloride tablets in treatment of myelofibrosis
Yi ZHANG ; Hu ZHOU ; Zhijian XIAO ; Jie JIN
Journal of Leukemia & Lymphoma 2024;33(7):392-398
Gecacitinib hydrochloride tablets (gecacitinib for short, and formerly known as "jaktinib hydrochloride tablets") is a novel JAK and ACVR1 inhibitor, which not only blocks the JAK-STAT signaling pathway by inhibiting the activities of JAK1, JAK2, JAK3, and TYK2, thereby alleviating inflammation and splenomegaly symptoms, but also reduces hepcidin transcription by inhibiting ACVR1 activity, thereby improving iron metabolism imbalance and anemia. Data from phases Ⅱ and Ⅲ clinical trials suggest that gecacitinib can both alleviate splenomegaly and reduce constitutional symptoms in patients with myelofibrosis (MF) who are na?ve to JAK inhibitors or have been exposed to ruxolitinib, as well as improve anemia in patients with MF. This article describes the mechanisms of action, pharmacokinetic characteristics, clinical efficacy, and treatment-related adverse effects of gecacitinib in the treatment of MF, providing references for the rational application of this drug in MF.
9.The evaluation of blood glucose and blood lipid changes and non-pharmacological intervention effects in gestational diabetes mellitus patients at different gestational weeks based on insulin sensitivity index differences of homeostasis model assessment 2
Xia ZHOU ; Ruying LIANG ; Qingyun ZHAO ; Zhi BAI ; Zhijian WANG ; Chunwei MOU
Chinese Journal of Postgraduates of Medicine 2024;47(10):898-903
Objective:To investigate the changes of blood glucose and blood lipid in gestational diabetes mellitus (GDM) patients with different insulin sensitivity during pregnancy and the effect of non-drug intervention.Methods:Data of 240 pregnant women with GDM and 240 healthy pregnant women were collected from July 1 to September 1, 2023 in Shijing People′s Hospital in Baiyun District and other five hospital. The insulin sensitivity index (ISI) was calculated by homeostasis model assessment 2(HOMA2) model, according to the 25th percentile of ISI of normal pregnant women, GDM patients were divided into insulin sensitive group (group A) and insulin sensitive deficiency group (group B), and group A and group B were divided into two groups according to 36-week blood glucose control: group A1 with good blood glucose control (group A1 and group B1) and group A2 with bad blood glucose control (group A2 and group B2). The age, body mass index (BMI) before pregnancy, fasting plasma glucose (FPG), blood lipids and blood glycated hemoglobin (HbA 1c ) in the first trimester, blood glucose and blood lipids in the second trimester were compared at the 28th, 32nd and 36th weeks of gestation, the number of cases, blood glucose, blood lipids and non-drug intervention were measured. Results:There were 166 cases in group A and 74 cases in group B. Blood glucose and blood lipid were normal in early pregnancy. There was no significant difference in blood glucose between group A and group B during the second trimester. The levels of blood lipids were significantly higher than those during the first trimester, and the levels of triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) were significantly higher than those during the first trimester. The number of pregnant women in group A1 was significantly more than that in group A2 in the third trimester ( P = 0.01), and the number of pregnant women in group B1 was more than that in group B2 at 28 weeks ( P = 0.01). At 32 weeks, the number of pregnant women in group B1 and group B2 was similar ( P = 0.31). At 36 weeks, the number of pregnant women in group B1 was significantly lower than that in group B2 ( P = 0.01). In the third trimester of pregnancy, the levels of blood glucose in group B2 were higher than those in group A2 ( P<0.05). The levels of TG and LDL-C in group A2 and group B2 were higher than those in group A1 and group B1 respectively, high-density lipoprotein cholesterol (HDL-C) was lower than that in group A1 and group B1( P<0.05), and there was no significant difference in TC between group A2 and group A1 at 28 and 32 weeks ( P>0.05), but it was significantly higher at 36 weeks ( P = 0.01). In the third trimester of pregnancy, diet control was the most common (91.7%, 87.7%, 81.6%, respectively) in group A ( P>0.05). The proportions of diet-only and diet-plus exercise interventions were similar in group B1 at 28 weeks and 32 weeks (52.9% vs. 47.1%, 45.7% vs. 54.3%)( P = 0.072, 0.113). At the 36 weeks, the main intervention was diet combined with exercise (73.3%). In group B2, dietary intervention (69.6%, 71.8%, 69.5%) was the main cause of poor control of blood glucose. Conclusions:In GDM patients with insulin sensitivity deficiency, the blood glucose and blood lipids in the second trimester are obviously increased, and the abnormality in the third trimester is even greater.
10.Identification of USP2 as a novel target to induce degradation of KRAS in myeloma cells.
Yingying WANG ; Youping ZHANG ; Hao LUO ; Wei WEI ; Wanting LIU ; Weiwei WANG ; Yunzhao WU ; Cheng PENG ; Yanjie JI ; Jianfang ZHANG ; Chujiao ZHU ; Wenhui BAI ; Li XIA ; Hu LEI ; Hanzhang XU ; Leimiao YIN ; Wei WENG ; Li YANG ; Ligen LIU ; Aiwu ZHOU ; Yueyue WEI ; Qi ZHU ; Weiliang ZHU ; Yongqing YANG ; Zhijian XU ; Yingli WU
Acta Pharmaceutica Sinica B 2024;14(12):5235-5248
Inducing the degradation of KRAS represents a novel strategy to combat cancers with KRAS mutation. In this study, we identify ubiquitin-specific protease 2 (USP2) as a novel deubiquitinating enzyme of KRAS in multiple myeloma (MM). Specifically, we demonstrate that gambogic acid (GA) forms a covalent bond with the cysteine 284 residue of USP2 through an allosteric pocket, inhibiting its deubiquitinating activity. Inactivation or knockdown of USP2 leads to the degradation of KRAS, resulting in the suppression of MM cell proliferation in vitro and in vivo. Conversely, overexpressing USP2 stabilizes KRAS and partially abrogates GA-induced apoptosis in MM cells. Furthermore, elevated USP2 levels may be associated with poorer prognoses in MM patients. These findings highlight the potential of the USP2/KRAS axis as a therapeutic target in MM, suggesting that strategically inducing KRAS degradation via USP2 inhibition could be a promising approach for treating cancers with KRAS mutations.

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