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

{"title":"[Live-combined <i>Bifidobacterium, Lactobacillus,</i> and <i>Enterococcus</i> improves heat tolerance and attenuates systemic inflammatory injury in heat-stroke rats via modulation of gut microbiota and intestinal barrier].","authors":"Jiangbo Xie, Zhengbiao Xue, Shuchang Ding, Peishan Wen, Yanhua Wen","doi":"10.3724/zdxbyxb-2025-0929","DOIUrl":"10.3724/zdxbyxb-2025-0929","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the ameliorative effects of live-combined <i>Bifidobacterium, Lactobacillus</i>, and <i>Enterococcus</i> (LCBLE) on heat tolerance and systemic inflammatory injury in rats with heat stroke, and to explore its underlying mechanisms.</p><p><strong>Methods: </strong>Rats were randomly divided into blank control, LCBLE control, model control, and LCBLE treatment groups. The LCBLE-treated groups received daily intragastric administration of LCBLE for 7 consecutive days, while the control groups received equal volumes of normal saline. On day 8, heat stroke was induced in the model control and LCBLE treatment groups. Core body temperature, body weight, and survival rate were monitored. Serum inflammatory cytokines were measured by enzyme-linked immunosorbent assay, and intestinal barrier function was assessed by blood biomarkers. Tight junction proteins zonula occludens-1 (ZO-1) and occludin were localized by immunofluorescence, intestinal ultrastructure was observed by transmission electron microscopy, and pathological morphology was evaluated by hematoxylin-eosin staining. Gut microbial composition was analyzed by 16S rRNA sequencing.</p><p><strong>Results: </strong>LCBLE pretreatment significantly reduced peak core body temperature [(42.03±0.43) ℃ <i>vs.</i> (43.21±0.33) ℃, <i>P</i><0.01], attenuated post-model weight loss [(307.8±11.3) g <i>vs.</i> (286.7±12.6) g, <i>P</i><0.05 ], and improved 24 h survival rate (77.8% <i>vs.</i> 55.6%, <i>P</i><0.05) compared with the model control group. Serum levels of tumor necrosis factor-α, IL-6, and IL-1β were significantly lower in the LCBLE treatment group (all <i>P</i><0.01), along with reduced pathological scores in all intestinal segments (all <i>P</i><0.01). LCBLE also restored the expression and distribution of ZO-1 and occludin, preserved intestinal epithelial ultrastructure, and markedly decreased serum D-lactate, intestinal fatty acid-binding protein, and endotoxin levels (all <i>P</i><0.01). 16S rRNA sequencing revealed that LCBLE significantly increased the relative abundances of <i>Bifidobacterium</i> and <i>Lactobacillus</i> in the gut.</p><p><strong>Conclusions: </strong>Pretreatment with LCBLE improves heat tolerance and alleviates systemic inflammation in heat-stroke rats, likely through regulating gut microbiota and maintaining intestinal barrier integrity.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"1-11"},"PeriodicalIF":0.0,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148391871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Ecological analysis of the association between dietary factors and thyroid carcinoma incidence based on GBD 2021 data].","authors":"Keyu Chen, Yanting Duan, Jiajie Xu","doi":"10.3724/zdxbyxb-2025-0819","DOIUrl":"10.3724/zdxbyxb-2025-0819","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;To examine the association between dietary factors and thyroid carcinoma incidence.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Data on thyroid carcinoma incidence and per capita intake of 15 dietary factors in 194 countries and territories from 1990 to 2021 were extracted from the Global Burden of Disease (GBD) 2021 database. At the dietary factor level, collinearity diagnostics were first performed, continuous dietary exposure variables were standardized using Z-scores before model fitting, and Bayesian generalized linear mixed models with a gamma distribution and log link function were fitted using the age-standardized incidence rate of thyroid carcinoma as the outcome to estimate posterior regression coefficients and rate ratios (per one-standard-deviation increase in each dietary exposure). At the dietary pattern level, principal component analysis was used to derive dietary patterns. After calculating and standardizing the dietary pattern scores, the statistical strength of the association between different dietary patterns and the age-standardized incidence rate of thyroid carcinoma was evaluated. Heterogeneity in the associations was further assessed by stratified analyses according to the sociodemographic index (SDI), sex, and age.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;From 1990 to 2021, the global age-standardized incidence rate of thyroid carcinoma increased and showed marked regional variation. Incidence remained consistently higher in females than in males, and the age-specific incidence rates increased with age. Analysis of dietary exposure indicated that intake of dietary fiber, legumes, and nuts increased globally, whereas trans fat intake generally declined. Intake patterns of sugar-sweetened beverages and animal-source foods showed pronounced SDI-related differences. Bayesian generalized linear mixed model identified 11 factors significantly associated with the age-standardized incidence rate of thyroid carcinoma. Intake of legumes, fruits, sugar-sweetened beverages, red meat, trans fats, and sodium was positively associated with thyroid carcinoma incidence, whereas intake of nuts, dietary fiber, processed meat, milk, and vegetables was negatively associated with thyroid carcinoma incidence. Three dietary patterns were identified, scores for pattern 1 (characterized by high loadings of red meat, processed meat, sugar-sweetened beverages, and milk) and pattern 2 (characterized by high loadings of fruits, legumes, vegetables, and polyunsaturated fatty acids, accompanied by a moderate loading of sugar-sweetened beverages) were positively associated with thyroid carcinoma incidence. In contrast, the score for dietary pattern 3 (characterized by high loadings of nuts and omega-3 fatty acids) was negatively associated with thyroid carcinoma incidence.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The global increase in thyroid carcinoma incidence may be associated with changes in dietary structure, especially in medium-development","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"540-550"},"PeriodicalIF":0.0,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13388239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148259494","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":"[En-bloc resection of thyroid carcinoma using recurrent laryngeal nerve tunnel dissection combined with mesothyroid excision: a retrospective analysis of 174 cases].","authors":"Kai Zhao, Heng Xia, Minghua Ge, Xingyu Huang, 加 杰 徐","doi":"10.3724/zdxbyxb-2025-0817","DOIUrl":"10.3724/zdxbyxb-2025-0817","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the application value of recurrent laryngeal nerve tunnel dissection combined with mesothyroid excision in en-bloc resection for thyroid carcinoma.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 174 patients with thyroid carcinoma diagnosed by preoperative fine-needle aspiration cytology who underwent surgery at Shaoxing Central Hospital from January 2020 to May 2024. These patients (modified surgery group) received en-bloc resection using recurrent laryngeal nerve tunnel dissection combined with mesothyroid excision, including 143 cases of unilateral radical thyroidectomy, 24 cases of bilateral radical thyroidectomy, and 7 cases of isthmus thyroidectomy. A total of 178 patients diagnosed by preoperative fine-needle aspiration cytology who underwent conventional two-step surgery by the same surgical team during the same period were selected as the conventional surgery group, including 160 cases of unilateral radical thyroidectomy and 18 cases of bilateral radical thyroidectomy.</p><p><strong>Results: </strong>All surgeries were completed successfully. Compared with the conventional surgery group, the modified surgery group showed superior outcomes in terms of postoperative temporary recurrent laryngeal nerve palsy, the number of autologous parathyroid glands transplanted, and the number of lymph nodes dissected from the central compartment and level ⅣB (all <i>P</i><0.05). And for patients undergoing unilateral radical thyroidectomy, operative time was shortened (<i>P</i><0.05). As of May 25, 2026, the follow-up period ranged from 15 to 77 months; no adverse events such as recurrence of thyroid carcinoma were reported.</p><p><strong>Conclusions: </strong>The modified en-bloc resection of thyroid carcinoma using recurrent laryngeal nerve tunnel dissection combined with mesothyroid excision is convenient to perform, achieves thorough lymph node dissection, and provides reliable protection of the recurrent laryngeal nerve and parathyroid glands, which is worthy of clinical application.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"571-578"},"PeriodicalIF":0.0,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13388237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148303303","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":"[Inhibitory effect of lonafarnib on anaplastic thyroid carcinoma cells and xenograft tumor growth in nude mice].","authors":"Jiaxin Li, Yuchen Gao, Yanting Duan, Jiajie Xu","doi":"10.3724/zdxbyxb-2025-0795","DOIUrl":"10.3724/zdxbyxb-2025-0795","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the inhibitory effect of the farnesyltransferase inhibitor lonafarnib on anaplastic thyroid carcinoma (ATC), and to elucidate the underlying mechanisms.</p><p><strong>Methods: </strong>The anti-proliferative effect of lonafarnib on ATC cell lines (8505C, CAL62) was assessed using CCK-8 assay. Cell migration and invasion were evaluated by Transwell assay. Apoptosis was detected by flow cytometry. Western blotting was used to measure protein expression levels of Ras, extracellular signal-regulated kinase (ERK), phosphorylated ERK, poly ADP-ribose polymerase (PARP), cleaved PARP, cysteine aspartic acid specific protease-3 (Caspase-3), cleaved Caspase-3, gasdermin E (GSDME), and GSDME N-terminal fragment (GSDME-N). A subcutaneous xenograft model was established in female BALB/c nude mice (4-6 weeks old). 8505C cells (1×10⁶) were injected into the right back of each mouse. When tumor volume reached 100-150 mm³, the mice were randomly divided into three groups (<i>n</i>=4 per group): blank control (normal saline by gavage every other day), low-dose lonafarnib (25 mg/kg by gavage every other day), and high-dose lonafarnib (50 mg/kg by gavage every other day). Treatment lasted for 15 days. Tumor volume and body weight were measured every two days. At the endpoint, tumors were excised and weighed.</p><p><strong>Results: </strong>Lonafarnib significantly inhibited the proliferation of ATC cells in a concentration-dependent manner, with superior efficacy compared to cobimetinib and lenvatinib. After treatment with 5, 10, and 20 μmol/L lonafarnib, the numbers of migrated and invaded 8505C and CAL62 cells were markedly reduced, and the apoptosis rates were increased (all <i>P</i><0.05). Mechanistically, lonafarnib treatment in ATC cells downregulated Ras protein expression, decreased the levels of total ERK, phosphorylated ERK, and PARP, and led to overall decreasing trends in Caspase-3 and GSDME expression. Concurrently, cleaved PARP increased in a concentration- and time-dependent manner, and both GSDME-N and cleaved Caspase-3 levels showed overall increasing trends. <i>In vivo</i>, the low-dose and high-dose lonafarnib groups exhibited significantly slower tumor growth compared with the control group. At the end of the observation period, tumor weights in lonafarnib groups were significantly lower than that in the control group (both <i>P</i><0.05). No significant body weight loss was observed, indicating good tolerability.</p><p><strong>Conclusions: </strong>Lonafarnib effectively suppresses the malignant progression of ATC both in ATC cell lines and in a BALB/c nude mouse xenograft model. The mechanism involves inhibition of Ras farnesylation and the downstream ERK signaling pathway, leading to activation of Caspase-3/PARP-mediated apoptosis and GSDME-mediated pyroptosis.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"495-504"},"PeriodicalIF":0.0,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13388233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148206369","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":"[Network pharmacology-based investigation of the therapeutic efficacy and molecular targets of Xiangsha Liujunzi decoction in thyroid carcinoma].","authors":"Kaihuai Huang, Yunye Liu, Ruimin Liang, Guowan Zheng, Lei Zhu, Fahuan Song, Yawen Guo","doi":"10.3724/zdxbyxb-2025-0779","DOIUrl":"10.3724/zdxbyxb-2025-0779","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;To explore the active components and potential molecular mechanisms of Chinese medicine Xiangsha Liujunzi decoction (XSLJZ) in the treatment of thyroid carcinoma.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Active components and corresponding targets of XSLJZ were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Thyroid cancer-related targets were collected from seven bioinformatics databases, including GeneCards, Online Mendelian Inheritance in Man Database (OMIM), DISGENET, DrugBank, The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Therapeutic Target Database (TTD). A protein-protein interaction (PPI) network and a multi-level \"XSLJZ-medicinal materials-active components-potential targets-thyroid carcinoma\" network were constructed to identify core targets. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed, followed by molecular docking to assess binding affinities. &lt;i&gt;In vitro,&lt;/i&gt; cell counting kit-8 (CCK-8), flow cytometry, colony formation, Transwell, and Western blotting assays were used to evaluate cell viability, death, proliferation ability, migration, and protein expression in 8505C and TPC1 thyroid carcinoma cells. &lt;i&gt;In vivo&lt;/i&gt;, a subcutaneous xenograft model was established in female BALB/c nude mice (6-8 weeks old, 15-16 g) by injecting 2×10&lt;sup&gt;6&lt;/sup&gt; 8505C cells. Mice were randomly divided into model control (vehicle), low-dose XSLJZ (200 mg/kg), and high-dose XSLJZ (400 mg/kg) groups (&lt;i&gt;n&lt;/i&gt;=6 per group), receiving daily gavage for 24 days. Tumor volume and body weight were measured every four days. Histopathological changes were observed by hematoxylin and eosin staining and immunohistochemical staining.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Five major active components of XSLJZ (isoliquiritigenin, naringenin, baicalein, nobiletin, and glycyrrhetinic acid) and 45 core targets for thyroid carcinoma were identified. XSLJZ and these five components significantly inhibited the proliferation of 8505C and TPC1 cells without notable toxicity to normal thyroid cells, with isoliquiritigenin showing the most prominent effect. Flow cytometry revealed that XSLJZ (16 mg/mL) induced up to (84.91±0.49)% death in TPC1 cells. Molecular docking showed low binding energies between isoliquiritigenin and protein kinase B 1 (Akt1), cysteine aspartic acid specific protease (Caspase)-3, Caspase-9, and poly ADP-ribose polymerase (PARP) (lowest －9.9 kcal/mol with PARP). XSLJZ and isoliquiritigenin dose-dependently suppressed colony formation and migration, downregu-lated receptor for advanced glycation end product (RAGE), phosphorylated phosphoino-sitide 3-kinase (PI3K), and phosphorylated Akt, upregulated B-cell lymphoma protein 2 associated X protein (BAX) and mitochondrial cytochrome c, and activated Caspase-3/9-mediated apoptosis and gasdermin E (GSDME)-dependent pyroptosis via the advanced glycation ","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"515-528"},"PeriodicalIF":0.0,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13388234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148303271","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":"[Methyltransferase-like protein 7B promotes glycolysis and malignant progression in papillary thyroid carcinoma cells via the USP28/HIF-1α axis].","authors":"Fengyu Xu, Qiuping Xie","doi":"10.3724/zdxbyxb-2025-0822","DOIUrl":"10.3724/zdxbyxb-2025-0822","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the expression of methyltransferase-like protein 7B (METTL7B) in papillary thyroid carcinoma (PTC) and elucidate its role and molecular mechanisms in tumor metabolic reprogramming and malignant progression.</p><p><strong>Methods: </strong>Public datasets from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were used to analyze METTL7B expression in PTC and its association with clinicopathological features. Immunohistochemistry on tissue microarrays was performed to validate METTL7B protein expression in clinical samples. Stable <i>METTL7B</i>-knockdown PTC cell lines were constructed, and knockdown efficiency was confirmed by quantitative real-time PCR (qRT-PCR) and Western blotting. Cell proliferation and clonogenic potential were evaluated using MTT and colony formation assays. Transcrip-tome sequencing was conducted in <i>METTL7B</i>-overexpressing cells to identify differentially expressed genes and enriched pathways, followed by qRT-PCR and Western blotting validation of METTL7B-mediated regulation of hypoxia-inducible factor 1α (HIF-1α). Cycloheximide chase and ubiquitination assays were used to assess the effect of METTL7B on HIF-1α protein stability, and the involvement of ubiquitin-specific protease 28 (USP28) was further examined. Lactate production and glucose uptake assays were performed to assess the impact of METTL7B and HIF-1α on glycolytic activity.</p><p><strong>Results: </strong>METTL7B was significantly upregulated in PTC tissues (<i>P</i><0.05) and positively correlated with lymph node metastasis (<i>P</i><0.05). <i>METTL7B</i> knockdown markedly suppressed PTC cell proliferation and colony formation (all <i>P</i><0.05), and markedly reduced the growth rate of PTC xenograft tumors in nude mice, with tumor volumes smaller than those in the control group (<i>P</i><0.05). Bioinformatics analysis suggested a strong association between METTL7B and the HIF-1α signaling pathway. <i>METTL7B</i> knockdown reduced HIF-1α protein levels without affecting its mRNA expression. Mechanistically, METTL7B inhibited the ubiquitination and degradation of HIF-1α, thereby maintaining its protein stability, and this process was mediated by USP28. Functional assays demonstrated that METTL7B enhanced glycolytic activity and malignant phenotypes of PTC cells by upregulating glycolysis-related genes through the USP28/HIF-1α axis.</p><p><strong>Conclusions: </strong>METTL7B promotes glycolysis and malignant progression in PTC cells by stabilizing HIF-1α through USP28-mediated deubiquitination.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"528-539"},"PeriodicalIF":0.0,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13388235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148303289","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 between mixed metal element exposure and the risk of thyroid carcinoma: a case-control study].","authors":"Zijian Zhan, Shuai Ma, Xiaopeng Zeng, Min Ye, Sihan Liu, Jiayi Song, Jianqing Zhang","doi":"10.3724/zdxbyxb-2025-0645","DOIUrl":"10.3724/zdxbyxb-2025-0645","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the association between urinary metal element concentrations and the risk of papillary thyroid carcinoma(PTC), to identify key risk factors, and to evaluate the combined effects and interactions of metal element exposure.</p><p><strong>Methods: </strong>A 1∶1 matched case-control study was adopted, including 189 pairs of newly diagnosed PTC patients and healthy controls matched by age and sex. Urinary concentrations of metal elements were measured using inductively coupled plasma mass spectrometry. Conditional logistic regression was applied to evaluate the associations of individual and mixed metal element exposure with PTC risk. Least absolute shrinkage and selection operator (LASSO) regression was used to screen for key metal elements. Weighted quantile sum (WQS) regression was employed to identify the main contributors to the mixture effect. Finally, a Bayesian kernel machine regression(BKMR) model was constructed to assess the overall effect of mixed metal element exposure and potential interactions among metal elements.</p><p><strong>Results: </strong>Multivariable conditional logistic regression showed that, in the model adjusted for multiple metal elements, elevated urinary concentra-tions of nickel, molybdenum, and barium were associated with an increased risk of thyroid carcinoma, with ORs (95%CIs) of 2.08 (1.53-2.96), 2.78 (1.68-4.77), and 2.42 (1.80-3.33), respectively; selenium and copper were negatively associated with thyroid carcinoma risk, with ORs (95%CIs) of 0.20 (0.15-0.37) and 0.31 (0.16-0.60), respectively. LASSO regression identified eight metal elements as key predictors: chromium, nickel, selenium, molybdenum, lead, iron, copper, and barium. WQS regression showed that nickel, barium, and molybdenum had relatively high weights in the positive constraint model, while copper and selenium had relatively high weights in the negative constraint model, suggesting that these metal elements may be major contributors to the overall mixture effect. The BKMR model indicated a nonlinear association between mixed metal element exposure and thyroid carcinoma risk, with potential effect modification among metal elements.</p><p><strong>Conclusions: </strong>Nickel, molybdenum, and barium exposure may be risk factors for thyroid carcinoma, copper may have a protective effect, while association between selenium and thyroid carcinoma risk showed an inverted U-shaped pattern. The effect of mixed metal element exposure was characterized by non-linearity and concentration dependence, with potential interactions among different metal elements.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"551-560"},"PeriodicalIF":0.0,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13388241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148206316","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":"[Preparation of retinoic acid and irinotecan co-loaded lipo-somes and their <i>in vitro</i> evaluation against anaplastic thyroid carcinoma].","authors":"Shixu Lyu, Yili Zhou, Yi Xu, Fan Yang","doi":"10.3724/zdxbyxb-2025-0811","DOIUrl":"10.3724/zdxbyxb-2025-0811","url":null,"abstract":"<p><strong>Objectives: </strong>To prepare retinoic acid (RA) and irinotecan (IRI) co‑loaded liposomes (RA-IRI@Lip) and evaluate their <i>in vitro</i> therapeutic effects against anaplastic thyroid carcinoma (ATC) and their ability to eliminate cancer stem cells (CSCs).</p><p><strong>Methods: </strong>RA-IRI@Lip was obtained through the co-encapsulation of RA and IRI within liposomes, using the thin-film hydration method. The particle size, Zeta potential, encapsulation efficiency, and <i>in vitro</i> release profiles of RA-IRI@Lip were characterized. Hemolysis assay was conducted to evaluate blood compatibility. Cellular uptake of FITC-labeled liposomes was assessed. The <i>in vitro</i> anti-ATC effects were evaluated by cell counting kit-8 (CCK‑8), calcein‑AM/PI staining, and Transwell assay. The synergistic effect of RA and IRI was analyzed using the combination index, while flow cytometry was performed to detect the proportions of aldehyde dehydrogenase-positive cells and CD133-positive cells.</p><p><strong>Results: </strong>The prepared RA-IRI@Lip had an average particle size of (210.3±5.2) nm, a polydispersity index less than 0.3, and Zeta potential of －(13.7±2.3) mV. The encapsulation efficiencies of RA and IRI were (88.1±2.9)% and (86.8±1.6)%, respectively. <i>In vitro</i> release studies showed that RA-IRI@Lip significantly delayed the release of both RA and IRI, with 48-h cumulative release rates of (66.2±3.6)% and (77.7±4.1)%, respectively. Hemolysis assays demonstrated that all tested concentrations of RA-IRI@Lip exhibited hemolysis rates below 3%, indicating good hemocompatibility. Liposomes can be efficiently taken up by ATC cells after FITC labeling. CCK-8 and calcein-AM/PI staining demonstrated that RA-IRI@Lip significantly inhibited the viability of ATC cells and promoted cell death, with an IC₅₀ significantly lower than those of the free IRI group and the free RA+IRI group (both <i>P</i><0.01). Combination index analysis demonstrated that both the free RA+IRI group and the RA-IRI@Lip group exhibited synergistic effects (combination index <1), with stronger synergism observed in the RA-IRI@Lip group. Transwell assay results demonstrated that RA-IRI@Lip exerted the most significant inhibitory effect on the migration and invasion of ATC cells. Flow cytometry results showed that RA-IRI@Lip significantly decreased the proportions of aldehyde dehydrogenase-positive cells and CD133-positive cells (both <i>P</i><0.01).</p><p><strong>Conclusions: </strong>RA-IRI@Lip was successfully prepared, achieving synergistic effects of differentiation therapy and chemotherapy of RA and IRI, thereby effectively eliminating ATC cells and CSCs.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"505-514"},"PeriodicalIF":0.0,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13388238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148259564","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 on the roles of mitochondrial fusion, fission, and mitophagy in burn wound healing​].","authors":"Zehao Li, Weixue Jin, Songxue Guo","doi":"10.3724/zdxbyxb-2026-0134","DOIUrl":"10.3724/zdxbyxb-2026-0134","url":null,"abstract":"<p><p>Mitochondria, known as the \"energy factory\" of cells, play a critical role in burn wound healing owing to their structural and functional stability. Following burn injury, mitochondrial damage exacerbates inflammatory responses, triggers endogenous apoptotic pathways, and reduces adenosine triphosphate synthesis, thereby delaying tissue repair. The dynamic balance between mitochondrial fusion and fission, together with mitophagy, is a key regulatory mechanism that maintains mitochondrial structural integrity and functional stability. Moderate mitochondrial fission promotes wound healing, whereas excessive fission induces overproduction of reactive oxygen species and inflammatory cytokines, which is detrimental to repair. Mitochondrial fusion may confer benefits to wound healing, and mitophagy alleviates apoptosis and oxidative stress, thereby regulating multiple stages of burn wound healing. This review focuses on the maintenance of the mitochondrial fusion-fission balance and mitophagy, elaborates their specific roles in burn wound repair, and discusses the clinical prospects of targeting these mechanisms for the prevention and treatment of post-burn injuries.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"579-586"},"PeriodicalIF":0.0,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13388236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148139282","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":"[A nomogram combining ultrasound radiomics and clinical features for predicting pathological invasiveness of papillary thyroid carcinoma].","authors":"Han Liu, Chunjie Hou, Min Wei, Kefeng Lu, Litao Sun, Jinglan Tang","doi":"10.3724/zdxbyxb-2025-0746","DOIUrl":"10.3724/zdxbyxb-2025-0746","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;To develop a nomogram model combining ultrasound radiomics and clinical features and to evaluate its predictive value for pathological invasiveness of papillary thyroid carcinoma (PTC).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This study included 224 patients diagnosed with PTC between January 2024 and May 2025 at Zhejiang Provincial People's Hospital. Baseline clinical data, laboratory findings, and raw ultrasound images were collected. The patients were randomly divided into a training cohort (&lt;i&gt;n&lt;/i&gt;=179) and a testing cohort (&lt;i&gt;n&lt;/i&gt;=45) at an 8∶2 ratio. Additionally, 42 patients diagnosed with PTC from June to November 2025 were enrolled as an independent validation cohort. Pathological invasiveness was defined as the presence of one or more of the following features: extrathyroidal extension, vascular invasion, perineural invasion, intraglandular dissemination, extra-glandular invasion, central or lateral cervical lymph node metastasis, or high-risk subtypes. Univariate analysis was performed on 11 candidate clinical features, followed by stepwise logistic regression to identify independent predictors and to construct a clinical feature-based model. Ultrasound radiomics features were screened using Mann-Whitney U test, Spearman's correlation analysis (threshold 0.9) with greedy recursive elimination, and least absolute shrinkage and selection operator (LASSO) regression. The selected features were then input into eight machine learning algorithms to build predictive models, and the optimal algorithm was selected based on the area under the receiver operating characteristic (ROC) curve (AUC). A nomogram was subsequently constructed by integrating the clinical model and the ultrasound radiomics model into a logistic regression framework. The discriminative ability, calibration, and clinical utility of the nomogram were assessed using ROC curves, calibration curves, and clinical decision curves.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The clinical feature model based solely on nodule size achieved AUCs of 0.889 (95%CI: 0.843-0.935) and 0.934 (95%CI: 0.860-0.973) in the training and testing cohorts, respectively. Thirteen ultrasound radiomics features were selected. The radiomics model built with logistic regression yielded AUCs of 0.846 (95%CI: 0.791-0.902) and 0.939 (95%CI: 0.871-1.000) in the training and testing cohorts, respectively. The nomogram combining ultrasound radiomics and clinical features achieved AUCs of 0.902 (95%CI: 0.858-0.945) in the training cohort, 0.982 (95%CI: 0.953-1.000) in the testing cohort, and 0.803 (95%CI: 0.665-0.941) in the independent validation cohort. Calibration curves demonstrated good agreement between predicted and observed probabilities, and clinical decision curves indicated favorable net clinical benefit.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;A nomogram model combining ultrasound radiomics and clinical features was successfully developed, which exhibited good discrimination, calibration,","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"485-494"},"PeriodicalIF":0.0,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13388242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148144695","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}