Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences最新文献

{"title":"[Haploinsufficiency of A20 in a family caused by a heterozygous deletion in the <i>TNFAIP3</i> gene].","authors":"Cuili Yi, Jihong Xiao","doi":"10.3724/zdxbyxb-2025-0545","DOIUrl":"10.3724/zdxbyxb-2025-0545","url":null,"abstract":"<p><p>The proband was a 3-year-4-month-old boy who had experienced recurrent diarrhea, fever, joint swelling and pain for more than a year accompanied by oral and perianal ulcers. Gastrointestinal endoscopy revealed multiple colorectal ulcers. The proband's 36-year-old father had a three-year history of oral ulcers and a one-year history of recurrent diarrhea; gastroscopy showed chronic non-atrophic gastritis with erosion and duodenitis, while colonoscopy was unremarkable. Whole exome sequencing revealed that the proband and his parents had no pathogenic single nucleotide variants or small insertions/deletions. Subsequent copy number variation analysis identified a heterozygous deletion of exons 2-9 in the tumor necrosis factor-α-induced protein 3 (TNFAIP3) gene in both the proband and his father, which was confirmed by quantitative PCR. Based on the clinical manifestations and genetic findings, the proband and his father were diagnosed with haploinsufficiency of A20 (HA20). Therefore, in patients with suspected HA20 presenting early-onset Behçet's syndrome-like manifestations, copy number variation analysis should be performed when whole exome sequencing fails to detect single nucleotide variants or small insertions/deletions in the <i>TNFAIP3</i> gene.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"332-337"},"PeriodicalIF":0.0,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13154121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147575373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Clinical characteristics and outcomes of children with rheu-matoid factor-positive polyarticular juvenile idiopathic arthritis].","authors":"Yue Zhou, Jianqiang Wu, Meiping Lu","doi":"10.3724/zdxbyxb-2025-0574","DOIUrl":"10.3724/zdxbyxb-2025-0574","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;To compare the clinical characteristics and outcomes between patients with rheumatoid factor (RF)-positive and RF-negative polyarticular juvenile idiopathic arthritis (pJIA).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A retrospective analysis was conducted on clinical data of 131 children diagnosed with pJIA at the Children's Hospital, Zhejiang University School of Medicine from January 2019 to January 2025. Patients were divided into an RF-positive group (&lt;i&gt;n&lt;/i&gt;=59) and an RF-negative group (&lt;i&gt;n&lt;/i&gt;=72) based on serum RF status. Disease activity was assessed using the Juvenile Arthritis Disease Activity Score-27 (JADAS-27). All patients were followed for at least 6 months, with a maximum follow-up duration of 6 years. Clinical features, laboratory findings, and outcomes were compared between the two groups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Among the 131 pJIA patients, 122 (93.1%) had high disease activity at baseline. Compared with the RF-negative group, the RF-positive group had a higher proportion of females (58.3% &lt;i&gt;vs&lt;/i&gt;. 84.7%, &lt;i&gt;P&lt;/i&gt;&lt;0.01), an older age at onset (7.14±3.98 years &lt;i&gt;vs&lt;/i&gt;. 8.86±4.02 years, &lt;i&gt;P&lt;/i&gt;&lt;0.05), and a higher prevalence of interstitial lung disease (4.2% &lt;i&gt;vs&lt;/i&gt;. 23.7%, &lt;i&gt;P&lt;/i&gt;&lt;0.01). The most frequently affected joints were the wrist in the RF-positive group, and the knee joints in the RF-negative group. At baseline, serum levels of IL-2, IL-6, IL-10, and tumor necrosis factor-α were significantly higher in the RF-positive group than those in the RF-negative group (all &lt;i&gt;P&lt;/i&gt;&lt;0.05). A total of 101 patients (77.1%) received biologic-targeted therapies, 46 (78.0%) in RF-positive group, and 55 (76.4%) in RF-negative group. Among them, 23 RF-positive patients (50.0%) and 12 RF-negative patients (21.8%) required two or more biologic-targeted drugs. RF positivity was identified as an independent risk factor for the use of two or more biologic-targeted drugs (OR=3.232, 95%CI: 1.109-9.421, &lt;i&gt;P&lt;/i&gt;&lt;0.05). Both groups showed significant reductions in JADAS-27 scores at 3, 6, 12, 24, 36, 48, 60, 72 months after treatment initiation compared with baseline (all &lt;i&gt;P&lt;/i&gt;&lt;0.01), with no significant differences in JADAS-27 scores or remission rates between the two groups at any follow-up time point (all &lt;i&gt;P&lt;/i&gt;&gt;0.05). The median time to achieve first clinical remission after treatment was 24 months in both groups (&lt;i&gt;P&lt;/i&gt;&gt;0.05). No significant differences were observed in remission rates or the proportion of patients requiring two or more biologic-targeted drugs among different types of biologic-targeted drugs (all &lt;i&gt;P&lt;/i&gt;&gt;0.05).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Children with RF-positive pJIA showed higher baseline inflammatory status and a higher incidence of pulmonary involvement, yet they achieved comparable remission rates to those with RF-negative pJIA. Biologic-targeted therapies may contribute to improved remission rates and outcomes, but RF-positive patients may require switching or","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"285-293"},"PeriodicalIF":0.0,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13154140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147677091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Research progress of the ULBP-NKG2D axis in autoimmune diseases].","authors":"Jiani Ma, Jing Wu, Yanliang Jin","doi":"10.3724/zdxbyxb-2025-0692","DOIUrl":"10.3724/zdxbyxb-2025-0692","url":null,"abstract":"<p><p>The activating receptor natural killer group 2 member D (NKG2D) and its ligands, the UL16-binding protein (ULBP), play pivotal roles in autoimmune diseases, characterized by multidimensional regulatory features. This review employs a three-dimensional framework of \"ligand supply-ligand fate-receptor regulation\" to analyze the research progress of the ULBP-NKG2D axis in autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, multiple sclerosis, and Crohn disease. In systemic lupus erythematosus, the axis involves both peripheral immune suppression (driven by receptor internalization) and local tissue immune attack, collectively shaping the complex pathology. In rheumatoid arthritis, the core pathological dysre-gulation of the axis is concentrated in the inflammatory synovial microenvironment: membrane-bound ligands derived from synovial fibroblasts directly drive the cytotoxicity of local effector cells, exacerbating joint inflammatory damage, while these ligands may be cleaved by a disintegrin and metalloprotease 10 (ADAM10) into soluble forms that enter the circulation and mediate peripheral immunosuppression. In type 1 diabetes, pancreatic β cells directly trigger NKG2D-mediated immune killing by upregulating membrane-bound ULBP proteins. In multiple sclerosis, astrocyte-derived ULBP4, in both membrane-bound and soluble forms, enhances the migration and pro-inflammatory capacity of effector cells. In Crohn disease, endoplasmic reticulum stress induces widespread ULBP expression in intestinal epithelial and endothelial cells, collectively mediating immune cell recruitment and amplifying local inflammation. This review also summarizes the current status of innovative drugs targeting the NKG2D receptor and their clinical translation progress, aiming to provide a reference for unraveling the complex immunopathology and developing precision immunotherapy strategies.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"352-363"},"PeriodicalIF":0.0,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13154127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Association of metabolic syndrome and its components with gout: an analysis based on a large-scale health survey database].","authors":"Jianbin Li, Wei Liu","doi":"10.3724/zdxbyxb-2025-0660","DOIUrl":"10.3724/zdxbyxb-2025-0660","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the association of metabolic syndrome (MetS) and its components with gout.</p><p><strong>Methods: </strong>This study utilized data from 28 130 adults aged ≥18 years in the National Health and Nutrition Examination Survey (NHANES) 2007-2018, among whom 1279 were identified as gout patients. Logistic regression was used to assess the associations of MetS and its components with gout. Restricted cubic spline (RCS) models were employed to examine non-linear dose-response relationships between metabolic indicators and gout. Subgroup analyses were performed by age, sex, and body mass index (BMI), with interaction effects evaluated using the Wald test by including multiplicative interaction terms in the logistic regression models.</p><p><strong>Results: </strong>The prevalence of MetS was substantially higher in individuals with gout than in those without (66.9% <i>vs</i>. 33.3%). After adjusting for age, sex, BMI, smoking, and alcohol consumption, MetS was independently associated with gout (OR=2.55, 95%CI: 1.55-4.20, <i>P</i><0.01), with central obesity (OR=2.44, 95%CI: 1.55-3.85, <i>P</i><0.01) and hypertension (OR=1.70, 95%CI: 1.04-2.78, <i>P</i><0.05) showing the strongest associations. RCS analysis revealed J-shaped associations for BMI and fasting glucose, accelerating positive associations for waist circumference, mean systolic blood pressure, and triglyceride levels, and U-shaped associations for mean diastolic blood pressure and low-density lipoprotein cholesterol (LDL-C) levels (all <i>P</i><0.05). High-density lipoprotein cholesterol (HDL-C) showed a significant non-linear association, with the OR value of gout generally decreasing as HDL-C levels increased (<i>P</i><0.05). Subgroup analyses indicated that the association of MetS with gout was significantly stronger in females than that in males (OR: 5.07 <i>vs.</i> 2.34, interaction <i>P</i><0.05), and the association of diabetes with gout was more pronounced in those aged ≥50 years (OR=4.58) and in non-obese individuals (OR=5.21) (both interaction <i>P</i><0.01).</p><p><strong>Conclusions: </strong>MetS is independently associated with gout, exhibiting significant non-linear dose-response characteristics and population heterogeneity.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"311-320"},"PeriodicalIF":0.0,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13154120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147575308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Expression of Notch signaling pathway in children with Henoch-Schönlein purpura and its correlation with inflam-matory cytokines].","authors":"Huishan Chen, Feng Li, Ying Tang, Ping Zeng","doi":"10.3724/zdxbyxb-2025-0561","DOIUrl":"10.3724/zdxbyxb-2025-0561","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the expression of Notch signaling pathway-related genes in peripheral blood mononuclear cells (PBMCs) of children with Henoch-Schönlein purpura (HSP) and their correlation with inflammatory cytokine levels.</p><p><strong>Methods: </strong>A total of 66 children with initial-onset HSP (30 in the complex HSP group and 36 in the simple HSP group) treated at the Guangzhou Women and Children's Medical Center, along with 28 healthy controls, were enrolled. The messenger RNA (mRNA) expression levels of <i>NOTCH1</i>-<i>NOTCH4</i>, <i>JAG1</i>, <i>JAG2</i>, and <i>HES1</i> in PBMCs were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Serum levels of IL-1β, IL-4, IL-6, IL-17, interferon-γ, and tumor necrosis factor (TNF)-α were measured by enzyme-linked immunosorbent assay (ELISA). Spearman correlation analysis was performed to evaluate the relationships between <i>NOTCH1</i>/<i>NOTCH2</i> mRNA levels and the mRNA levels of the ligand-coding gene <i>JAG1</i>, the downstream target gene <i>HES1</i>, as well as inflammatory cytokine levels.</p><p><strong>Results: </strong>Compared with the healthy control group, both the simple and complex HSP groups showed significantly elevated mRNA levels of <i>NOTCH1</i>, <i>NOTCH2</i>, <i>JAG1</i>, and <i>HES1</i>, as well as increased serum levels of IL-17, interferon-γ, and TNF-α (all <i>P</i><0.05). Furthermore, the mRNA levels of <i>NOTCH1</i>, <i>NOTCH2</i>, and <i>HES1</i> were significantly higher in the complex HSP group than those in the simple HSP group (all <i>P</i><0.05). <i>NOTCH1</i> mRNA levels were positively correlated with <i>JAG1</i> and <i>HES1</i> mRNA levels, as well as with interferon-γ and TNF-α levels (all <i>P</i><0.05). <i>NOTCH2</i> mRNA levels were positively correlated with IL-17 and interferon-γ levels (both <i>P</i><0.05).</p><p><strong>Conclusions: </strong>The Notch signaling pathway is significantly activated during the acute phase of HSP and may participate in the immunopathological process by regulating the secretion of pro-inflammatory cytokines. The mRNA expression levels of <i>NOTCH1</i> and <i>NOTCH2</i> may correlate with disease severity, potentially serving as reference indicators for disease assessment.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"303-310"},"PeriodicalIF":0.0,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13154141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147634549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Dosage optimization of major components of Yinchenhao decoction for metabolic associated fatty liver disease and its mechanism: an experimental study].","authors":"Yanyan Gao, Ruyun Xue, Fangying Xu, Lin Chen, Jiannan Qiu, Xiaobing Dou","doi":"10.3724/zdxbyxb-2025-0323","DOIUrl":"10.3724/zdxbyxb-2025-0323","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;To investigate the optimal dose ratio and mechanisms of the primary active components in Yinchenhao decoction (geniposide, chlorogenic acid, and rhubarb polysaccharides) for ameliorating metabolic associated fatty liver disease (MAFLD).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;C57BL/6 mice were randomly divided into the normal control group, model control group, uniform design groups 1-6, and Yinchenhao decoction group; except for the normal control group, mice in all other groups were fed Western diets to establish MAFLD models, and after eight weeks of modeling, mice in the uniform design groups 1-6 and Yinchenhao decoction group were given the corresponding drugs by gavage. At 12 weeks, all mice were sacrificed: their body weight and liver weight were measured, hematoxylin-eosin staining was used to observe the histopathological changes of liver tissues, the plasma levels of alanine transaminase (ALT) and aspartate transaminase (AST) were measured, and the levels of total cholesterol (TC) and triglycerides (TG) in plasma and liver were measured. Based on these results, the optimal uniform design group was identified; subsequently, with plasma AST, plasma TG, and liver TC levels as screening indicators, the optimal dose ratio was obtained via a regression equation, which was further verified from functional indicators and tissue morphology. Meanwhile, glucose tolerance test and insulin tolerance test were conducted to evaluate glucose metabolic homeostasis and insulin sensitivity in mice, periodic acid-Schiff staining was used to observe glycogen accumulation, quantitative reverse transcription-polymerase chain reaction was employed to detect the mRNA expression of genes related to glycolipid metabolism and bile acid metabolism, Western blotting was performed to measure the protein expression of molecules involved in bile acid metabolism, and commercial kits were used to determine the plasma levels of total bilirubin (TBIL), direct bilirubin (DBIL), and total bile acid (TBA).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Combinations of geniposide, chlorogenic acid, and rhubarb polysaccharide all reduced the liver-to-body weight ratio, alleviated liver injury, and decreased lipid accumulation, among which the uniform design group 6 (200 mg/kg geniposide+160 mg/kg chlorogenic acid+340 mg/kg rhubarb polysac-charide) exhibited the optimal efficacy. Meanwhile, regression analysis indicated that the dosage ratio of uniform design group 6 was the optimal one for MAFLD intervention. Validation experiments showed that, compared with single-drug intervention, the optimal dosage ratio resulted in significantly lower body weight, as well as lower plasma levels of ALT, AST and TC in mice (all &lt;i&gt;P&lt;/i&gt;&lt;0.05), along with a more pronounced reduction in the area of hepatic lipid accumulation. Mechanistic investigation experiments demonstrated that intervention with the optimal dosage ratio significantly improved glucose tolerance and insulin sensitivi","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"210-221"},"PeriodicalIF":0.0,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13195734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145551218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Distribution characteristics of traditional Chinese medicine syndromes in patients with hepatolenticular degeneration across all age groups].","authors":"Daiping Hua, Lanting Sun, Qiaoyu Xuan, Shang Xiang, Shiheng Shi, Wenming Yang, Han Wang","doi":"10.3724/zdxbyxb-2025-0873","DOIUrl":"10.3724/zdxbyxb-2025-0873","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;To investigate the distribution of traditional Chinese medicine (TCM) syndrome patterns in hepatolenticular degeneration (Wilson disease, WD) and to characterize their variation across different age stages and clinical classifications.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A cross-sectional study was conducted on 2969 WD patients who visited the First Affiliated Hospital of Anhui University of Chinese Medicine between March 2020 and February 2025. Patients were divided into five age groups: childhood (3-&lt;14 years), adolescence (14-&lt;18 years), young adulthood (18-&lt;45 years), middle age (45-&lt;60 years), and old age (≥60 years). Meanwhile, the patients were divided into hepatic type, neurological type, other type and mixed type. Factor analysis was used to extract syndrome elements of disease location and disease nature, while cluster analysis summarized TCM syndrome patterns and analyzed their distribution across age stages and clinical classifications.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The primary TCM syndrome elements of disease location in WD were the liver (65.88%),spleen (44.73%), and kidney (32.47%). The core disease nature syndrome elements were dampness (37.59%), heat pathogen (37.42%), and phlegm (32.70%), accompanied by yin deficiency (31.83%) and blood stasis (27.01%). Six TCM syndrome patterns were identified: internal retention of damp-heat (26.34%), syndrome of intermin-gled phlegm and blood stasis (24.59%), syndrome of stagnation of liver qi and spleen deficiency (20.04%), syndrome of yin deficiency of liver and kidney (16.30%), syndrome of deficiency of both qi and blood (6.87%), and syndrome of yang deficiency of spleen and kidney (5.86%). The distribution of TCM syndrome patterns showed clear age-related characteristics: childhood was predominantly characterized by internal retention of damp-heat (28.33%) and syndrome of yin deficiency of liver and kidney (19.70%); adolescence by internal retention of damp-heat (28.09%) and syndrome of stagnation of liver qi and spleen deficiency (23.41%); young adulthood by syndrome of intermin-gled phlegm and blood stasis (27.66%) and internal retention of damp-heat (26.39%); middle age mainly by syndrome of intermin-gled phlegm and blood stasis (30.33%); and old age by syndrome of yin deficiency of liver and kidney (35.71%) and syndrome of stagnation of liver qi and spleen deficiency (28.57%). Regarding clinical classification, the distribution of TCM syndrome patterns also differed: internal retention of damp-heat (35.48%) was most prevalent in the hepatic type, syndrome of intermin-gled phlegm and blood stasis (36.52%) predominated in the neurological type, while the mixed type exhibited a complex pattern with co-occurrence of syndrome of intermin-gled phlegm and blood stasis (27.97%), internal retention of damp-heat (24.09%), and syndrome of stagnation of liver qi and spleen deficiency (21.70%).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The distribution of TCM syndromes in W","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"187-197"},"PeriodicalIF":0.0,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13195735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147677109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Chinese medicine Gandouling attenuates brain injury in hepatolenticular degeneration mice by inhibiting ferroptosis via the SIRT1/FoxO3 signaling pathway].","authors":"Kaijian Wu, Ni Wang, Dapeng Zhao, Wangyun Wei, Wanqing Zhang, Jing Zhang","doi":"10.3724/zdxbyxb-2025-0622","DOIUrl":"10.3724/zdxbyxb-2025-0622","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the mechanism by which the Chinese medicine Gandouling protects against brain injury in hepatolenticular degeneration (Wilson disease) through regulation of the silence information regulator 1 (SIRT1)/forkhead box protein O3 (FoxO3) pathway-mediated ferroptosis.</p><p><strong>Methods: </strong>TX mice were randomly divided into six groups: model control, Gandouling, resveratrol (SIRT1 activator), Gandouling+resveratrol, EX-527 (SIRT1 inhibitor), and Gandouling+EX-527 groups, with DL mice serving as the blank control group. After four weeks of intervention, neurological function was assessed using the Morris water maze test, wire hanging test, and pole test. Apoptosis in basal ganglia tissue was detected by TUNEL assay. Reactive oxygen species (ROS) levels in basal ganglia tissue were measured using the DCFH-DA method, while ferrous iron (Fe²⁺) and malondialdehyde (MDA) levels were determined by colorimetric assays. Immunofluorescence was used to evaluate the fluorescence intensity of SIRT1 and FoxO3. The protein expression levels of SIRT1, FoxO3, glutathione peroxidase 4 (GPX4), solute carrier superfamily 7 member 11 (SLC7A11), acid-CoA synthetase long-chain family 4 (ACSL4), ferritin heavy chain 1 (FTH1), and P53 were assessed by Western blotting, and the mRNA expression levels of <i>Sirt1</i> and <i>Foxo3</i> were quantified by qRT-PCR.</p><p><strong>Results: </strong>Compared with the blank control group, the model control group exhibited significant neurological impairments (prolonged escape latency, reduced platform crossing frequency, decreased grip score and prolonged turning and pole-climbing time), increased neuronal apoptosis, decreased transcription and expression of <i>Sirt1</i> (both <i>P</i><0.01), increased transcription (<i>P</i><0.05) and expression (<i>P</i><0.01) of <i>Foxo3</i>, and elevated levels of ROS, Fe²⁺, and MDA in basal ganglia tissue (all <i>P</i><0.01). Expression levels of ferroptosis-inhibiting proteins (GPX4, SLC7A11, FTH1) were decreased (all <i>P</i><0.01), while those of ferroptosis-promoting proteins (P53, ACSL4) were increased (both <i>P</i><0.05). Both Gandouling and resveratrol monotherapy significantly reversed the above alterations with comparable efficacy between the two treatments (all <i>P</i>>0.05) and combined Gandouling and resveratrol treatment exhibited synergistic effects. EX-527 exacerbated neurological impairments,neuronal apoptosis and ferroptosis (all <i>P</i><0.05). However, no significant differences were observed between the Gandouling+EX-527 group and the model control group (all <i>P</i>>0.05).</p><p><strong>Conclusions: </strong>Gandouling inhibits neuronal ferroptosis by regulating the SIRT1/FoxO3 signaling pathway, thereby improving neurological function in model mice.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"198-209"},"PeriodicalIF":0.0,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13195738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147634589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Anemoside B4 inhibits non-small cell lung cancer metastasis by modulating epithelial-mesenchymal transition mediated by the MAPK and Keap1/Nrf2 signaling pathways].","authors":"Qian Su, Lianting Liao, Lina Liu, Linyu Xiao, Yufang Shen, Shilin Yang, Renyikun Yuan, Hongwei Gao","doi":"10.3724/zdxbyxb-2025-0384","DOIUrl":"10.3724/zdxbyxb-2025-0384","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the effect and mechanism of Anemoside B4 (AB4) on non-small cell lung cancer (NSCLC) metastasis.</p><p><strong>Methods: </strong><i>In vitro</i>, the MTT assay was used to evaluate the effect of AB4 on the viability of human NSCLC cell lines A549 and H1975. Cell scratch and Transwell assays were performed to assess the effect of AB4 on the migration and invasion of A549 and H1975 cells induced by transforming growth factor-β1 (TGF-β1). Western blotting and immunofluorescence were used to detect the expression of proteins related to epithelial-mesenchymal transition (EMT), the mitogen-activated protein kinase (MAPK) signaling pathway, and the oxidative stress signaling pathway. <i>In</i><i>vivo</i>, a mouse model of melanoma lung metastasis was established by tail vein injection of B16-F10 cells to evaluate the effect of AB4 (20, 40 mg/kg) on melanoma lung metastasis. Blood routine parameters were measured, pathological changes in lung tissue were observed by hematoxylin and eosin staining, and the expression of EMT-, MAPK-, and oxidative stress signaling pathway-related proteins in lung tissue was analyzed by Western blotting.</p><p><strong>Results: </strong><i>In vitro</i>, the MTT assay showed that AB4 (5, 10, 20 μmol/L) had no cytotoxic effect. AB4 inhibited the migration and invasion of A549 and H1975 cells induced by TGF-β1; decreased the expression of N-cadherin, vimentin, Slug, and Snail while increasing E-cadherin expression in the EMT pathway; decreased Keap1 expression and increased Nrf2 expression in the oxidative stress pathway; and reduced the phosphorylation levels of JNK, ERK, and p38 in the MAPK pathway. <i>In</i><i>vivo</i>, AB4 alleviated weight loss, inhibited melanoma lung metastasis, and the mechanism may be related to the inhibition of EMT, oxidative stress, and the MAPK signaling pathway in the lung tissue of model mice.</p><p><strong>Conclusions: </strong>AB4 inhibits tumor metastasis by modulating EMT mediated by the MAPK and Keap1/Nrf2 signaling pathways.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"256-266"},"PeriodicalIF":0.0,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13195740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147677140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[<i>Angelica sinensis</i> polysaccharide ameliorates endometriosis in rats by restoring autophagic homeostasis via inhibition of Keap1/Nrf2/HO-1-mediated oxidative stress].","authors":"Jie Li, Xiao Li, Xia Ji, Yao Huang, Zhanli Wang","doi":"10.3724/zdxbyxb-2025-0459","DOIUrl":"10.3724/zdxbyxb-2025-0459","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the mechanism of <i>Angelica sinensis</i> polysac-charide (ASP) ameliorating endometriosis (EMT) via the Kelch-like epichlorohydrin-associated protein 1 (Keap1)/nuclear factor-erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway.</p><p><strong>Methods: </strong>SD rats were randomly divided into six groups (<i>n</i>=12 per group): normal control, model control, low-dose ASP, high-dose ASP, gestrinone, and high-dose ASP+recombinant Keap1 (rKeap1). EMT models were established in all groups except the normal control group. After successful modeling, the drugs were administered once daily for 4 weeks. The mass and volume of ectopic endometrial tissue were measured. Histopathological changes were evaluated using hematoxylin and eosin staining. Levels of reactive oxygen species, malondialdehyde, and superoxide dismutase (SOD) were measured using commercial kits. The number of autophagosomes was examined under transmission electron microscopy. The relative fluorescence intensity of microtubule-associated protein light chain 3 (LC3) in endometrial tissue was assessed by immunofluorescence staining. Western blotting was used to determine the protein expression levels of LC3-Ⅱ, LC3-Ⅰ, p62, Keap1, Nrf2 in the nucleus, and HO-1.</p><p><strong>Results: </strong>Compared with the normal control group, the model control group showed increased glandular proliferation, pronounced vacuolization of glandular cells, and substantial inflammatory cell infiltration in ectopic endometrial tissue. Levels of reactive oxygen species, malondialdehyde, p62, and Keap1 were significantly increased, while SOD levels, autophagosome numbers, and LC3 fluorescence intensity were significantly decreased (all <i>P</i><0.05). Protein expression levels of LC3-Ⅱ/LC3-Ⅰ, Nrf2 in the nucleus, and HO-1 were also significantly reduced (all <i>P</i><0.05). Compared with the model control group, the low- and high-dose ASP groups and the gestrinone group exhibited alleviated pathological damages, reduced mass and volume of ectopic endometrial tissues, decreased levels of reactive oxygen species, malondialdehyde, p62, and Keap1, and increased SOD levels, autophagosome numbers, LC3 fluorescence intensity, and protein expression levels of LC3-Ⅱ/LC3-Ⅰ, Nrf2 in the nucleus, and HO-1 (all <i>P</i><0.05). However, co-administration of rKeap1 reversed the inhibitory effects of high-dose ASP on oxidative stress and its restorative effects on autophagic homeostasis in EMT rats.</p><p><strong>Conclusions: </strong><i>Angelica sinensis</i> polysaccharide may ameliorate EMT in rats by inhibiting Keap1-mediated activation of the Nrf2/HO-1 pathway, thereby suppressing oxidative stress and restoring autophagic homeostasis.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"246-255"},"PeriodicalIF":0.0,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13195736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147595125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}