1.Pathogenesis Reasoning Chain-of-thought Supervision for Large Language Models: Syndrome Manifestation Recognition and Multidimensional Evaluation in Spleen-stomach Disorders
Shu-Han YANG ; Yu-Xin HU ; Xin-Yu YU ; Yu-Ying TU ; Yi-Chang ZANG ; Pan-Fei LI
Progress in Biochemistry and Biophysics 2026;53(5):1240-1263
ObjectiveThe essence of syndrome manifestation recognition in traditional Chinese medicine (TCM) is to infer the body’s latent pathogenesis state from clinical observational information, rather than to perform simple label matching. However, previous studies have largely modeled this task as syndrome pattern classification within a fixed label space, which does not adequately reflect the cognition process of TCM syndrome differentiation centered on pathogenesis reasoning, and is also insufficient to capture the openness, semantic variability, and cross-disease reusability of syndrome manifestation expression. This study aimed to investigate whether introducing pathogenesis reasoning chain-of-thought (PR-CoT) supervision into large language models (LLMs) could improve the quality and cognitive consistency of syndrome manifestation recognition and support cross-disease transfer. MethodsSyndrome manifestation recognition was formulated as a conditional generation task under the framework of clinical observational information (X)→pathogenesis structure (Z)→syndrome pattern output (Y), where Z serves as an explicit intermediate structural variable linking the clinical evidence and syndrome judgment. Within this framework, a PR-CoT-supervised dataset for syndrome manifestation recognition was constructed based on medical case records of spleen-stomach disorders. After preprocessing, information extraction, manual proofreading, and data cleaning, the dataset comprised 4 800 training cases, 400 development cases, and 400 test cases. Each sample was annotated with a structured PR-CoT consisting of three progressive levels: clinical information summarization, comprehensive pathogenesis analysis, and syndrome pattern output. Supervised fine-tuning was conducted on open-source LLMs, with an end-to-end model serving as the baseline. Qwen3-32B was used as the primary experimental model, and Qwen3-14B as the scale comparison model. A progressive multidimensional evaluation framework was further established, comprising a structural parsing level, a semantic similarity level, and an expert blind review level. At the structural parsing level, syndrome pattern expressions were decomposed into structural elements and evaluated using Precision, Recall, F1 score, and Jaccard similarity. At the semantic similarity level, independent LLMs scored the theoretical proximity between predicted and reference syndrome patterns. At the expert blind review level, three TCM experts independently evaluated model outputs on two dimensions: syndrome differentiation consistency and terminology standardization of syndrome patterns. In addition, zero-shot cross-disease transfer evaluation was conducted on gynecological and heart-system disorder test sets. ResultsAt the structural parsing level, PR-CoT supervision did not lead to a stable improvement in the element-wise overlap of syndrome pattern structural components. Compared with the corresponding baselines, neither Qwen3-32B nor Qwen3-14B showed consistent advantages in structural matching metrics after the introduction of PR-CoT supervision. In contrast, at the semantic similarity level, PR-CoT supervision produced stable positive gains across different model scales and evaluation systems. The average semantic score of Qwen3-32B increased from 6.425 8 in the baseline model to 6.585 0 after PR-CoT supervision, and that of Qwen3-14B increased from 5.870 0 to 5.964 2. At the expert blind review level, the overall score of Qwen3-32B (PR-CoT) was 7.026 0±0.107 7, higher than 6.416 3±0.288 9 for its baseline. In zero-shot cross-disease testing, the PR-CoT model still showed advantages in semantic evaluation and expert evaluation on both gynecological and heart-system disorder test sets, indicating a certain degree of transferability. ConclusionThe benefits of PR-CoT supervision are mainly reflected in TCM semantic consistency and clinical plausibility, rather than in improved hard matching of structural elements. These findings support understanding syndrome manifestation recognition as a process of generating and expressing latent pathogenesis structures, rather than as a classification task within a traditional fixed label space. By introducing pathogenesis reasoning as an explicit intermediate structure into the modeling process and combining it with a progressive multidimensional evaluation framework, this study provides a methodological pathway for intelligent TCM syndrome differentiation that integrates theoretical alignment, interpretability, and multi-level evaluation.
2.Pathogenesis Reasoning Chain-of-thought Supervision for Large Language Models: Syndrome Manifestation Recognition and Multidimensional Evaluation in Spleen-stomach Disorders
Shu-Han YANG ; Yu-Xin HU ; Xin-Yu YU ; Yu-Ying TU ; Yi-Chang ZANG ; Pan-Fei LI
Progress in Biochemistry and Biophysics 2026;53(5):1240-1263
ObjectiveThe essence of syndrome manifestation recognition in traditional Chinese medicine (TCM) is to infer the body’s latent pathogenesis state from clinical observational information, rather than to perform simple label matching. However, previous studies have largely modeled this task as syndrome pattern classification within a fixed label space, which does not adequately reflect the cognition process of TCM syndrome differentiation centered on pathogenesis reasoning, and is also insufficient to capture the openness, semantic variability, and cross-disease reusability of syndrome manifestation expression. This study aimed to investigate whether introducing pathogenesis reasoning chain-of-thought (PR-CoT) supervision into large language models (LLMs) could improve the quality and cognitive consistency of syndrome manifestation recognition and support cross-disease transfer. MethodsSyndrome manifestation recognition was formulated as a conditional generation task under the framework of clinical observational information (X)→pathogenesis structure (Z)→syndrome pattern output (Y), where Z serves as an explicit intermediate structural variable linking the clinical evidence and syndrome judgment. Within this framework, a PR-CoT-supervised dataset for syndrome manifestation recognition was constructed based on medical case records of spleen-stomach disorders. After preprocessing, information extraction, manual proofreading, and data cleaning, the dataset comprised 4 800 training cases, 400 development cases, and 400 test cases. Each sample was annotated with a structured PR-CoT consisting of three progressive levels: clinical information summarization, comprehensive pathogenesis analysis, and syndrome pattern output. Supervised fine-tuning was conducted on open-source LLMs, with an end-to-end model serving as the baseline. Qwen3-32B was used as the primary experimental model, and Qwen3-14B as the scale comparison model. A progressive multidimensional evaluation framework was further established, comprising a structural parsing level, a semantic similarity level, and an expert blind review level. At the structural parsing level, syndrome pattern expressions were decomposed into structural elements and evaluated using Precision, Recall, F1 score, and Jaccard similarity. At the semantic similarity level, independent LLMs scored the theoretical proximity between predicted and reference syndrome patterns. At the expert blind review level, three TCM experts independently evaluated model outputs on two dimensions: syndrome differentiation consistency and terminology standardization of syndrome patterns. In addition, zero-shot cross-disease transfer evaluation was conducted on gynecological and heart-system disorder test sets. ResultsAt the structural parsing level, PR-CoT supervision did not lead to a stable improvement in the element-wise overlap of syndrome pattern structural components. Compared with the corresponding baselines, neither Qwen3-32B nor Qwen3-14B showed consistent advantages in structural matching metrics after the introduction of PR-CoT supervision. In contrast, at the semantic similarity level, PR-CoT supervision produced stable positive gains across different model scales and evaluation systems. The average semantic score of Qwen3-32B increased from 6.425 8 in the baseline model to 6.585 0 after PR-CoT supervision, and that of Qwen3-14B increased from 5.870 0 to 5.964 2. At the expert blind review level, the overall score of Qwen3-32B (PR-CoT) was 7.026 0±0.107 7, higher than 6.416 3±0.288 9 for its baseline. In zero-shot cross-disease testing, the PR-CoT model still showed advantages in semantic evaluation and expert evaluation on both gynecological and heart-system disorder test sets, indicating a certain degree of transferability. ConclusionThe benefits of PR-CoT supervision are mainly reflected in TCM semantic consistency and clinical plausibility, rather than in improved hard matching of structural elements. These findings support understanding syndrome manifestation recognition as a process of generating and expressing latent pathogenesis structures, rather than as a classification task within a traditional fixed label space. By introducing pathogenesis reasoning as an explicit intermediate structure into the modeling process and combining it with a progressive multidimensional evaluation framework, this study provides a methodological pathway for intelligent TCM syndrome differentiation that integrates theoretical alignment, interpretability, and multi-level evaluation.
3.Meta-integration of qualitative studies on body image experience in breast cancer patients
Shu YANG ; Yihui LIN ; Zhihao HAN ; Linxia TANG ; Yunxia QIU ; Xiaoqin MA
Chinese Journal of Nursing 2025;60(14):1786-1792
Objective To systematically integrate the qualitative studies on body image experience in breast cancer patients,in order to provide references for the clinical formulation of corresponding intervention programs.Methods Systematical search was conducted for qualitative studies on the body image experiences of breast cancer patients in databases including PubMed,Web of Science,Cochrane Library,CINAHL,PsycINFO,CNKI,WanFang Database,VIP and CBM.The search period was from the establishment of the database to July 2024.The quality of the literature was evaluated using the 2016 edition of the qualitative research appraisal tool from the Evidence-Based Health Care Center of the Joanna Briggs Research Institute in Australia,and the results were integrated using the pooled integration method.Results A total of 14 pieces of the literature were included,and 36 research results were extracted and summarized into 7 new categories.Totally 3 integrated results were obtained,namely the negative impact of changes in body image,patients' self-adjustment and growth,and patients' need for external support.Conclusion Breast cancer patients are plagued by multiple body images.Medical staff should pay attention to the psychological state of patients,do a good job in health education,improve the understanding and support of the society,provide targeted professional guidance,promote the psychological adaptation of patients,meet the emotional needs of patients,establish multiple support systems,and improve the body image and quality of life of patients.
4.Diagnostic value of fecal calprotectin for assessing endoscopic activity in ulcerative colitis: comparison with conventional inflammatory markers
Qianqian XIA ; Ye GUO ; Wei HAN ; Yuzhe ZHOU ; Xiaoyan TANG ; Hong LYU ; Huijun SHU ; Gechong RUAN ; Hong YANG ; Jiaming QIAN
Chinese Journal of Inflammatory Bowel Diseases 2025;09(6):448-455
Objective:To evaluate the diagnostic performance of fecal calprotectin (FC) in predicting endoscopic activity of ulcerative colitis (UC), and to compare it with high-sensitivity C reactive protein (hsCRP) and erythrocyte sedimentation rate (ESR) .Methods:A cross-sectional stydy was conducted. UC patients diagnosed at Peking Union Medical College Hospital between May 2023 and July 2025 were retrospective enrolled. Patients were divided into the endoscopically active group and endoscopic remission group according to endoscopic activity. FC levels were measured using latex-enhanced turbidimetric immunoassay (LETIA). Receiver operating characteristic (ROC) curves and logistic regression models were used to assess diagnostic efficacy. Subgroup analyses were conducted according to disease extent.Results:A total of 166 UC patients were enrolled, including 92 males and 74 females with the age of 40.00 (32.00, 52.00) years old and disease course 5.00 (2.00, 10.75) years. Forty-six patients were assigned to the active group, while the remaining 120 were assigned to the remission group. FC levels were significantly higher in the active group than in the remission group (620.72 μg/g vs. 29.00 μg/g, P < 0.001), with an AUC of 0.894 at a cutoff value of 122.54 μg/g. hsCRP and ESR had lower AUC (0.712 and 0.736, respectively). The combination of FC, hsCRP, and ESR slightly improved specificity (AUC 0.898). FC was strongly correlated with the endoscopic activity ( r =0.669, P < 0.001) but not with disease extent. Conclusions:FC measured by latex-enhanced turbidimetric immunoassay had comparable diagnostic accuracy to ELISA-based methods commonly used abroad, and provided a reference cutoff value of 122.54 μg/g. FC outperforms hsCRP and ESR in assessing intestinal inflammation in UC and it is less affected by disease extent, making it a reliable non-invasive biomarker for UC monitoring.
5.Cross-sectional study of fecal calprotectin in predicting endoscopic activity in patients with Crohn's disease
Yuzhe ZHOU ; Qianqian XIA ; Ye GUO ; Wei HAN ; Xiaoyan TANG ; Hong LYU ; Huijun SHU ; Gechong RUAN ; Hong YANG ; Jiaming QIAN
Chinese Journal of Inflammatory Bowel Diseases 2025;09(6):462-468
Objective:To evaluate the predictive efficacy of fecal calprotectin (FC) for endoscopic activity in patients with Crohn's disease (CD) .Methods:A cross-sectional study was conducted and patients diagnosed as CD at Peking Union Medical College Hospital from June 2023 to September 2025 were enrolled consecutively. Data was collected including general information, laboratory tests [hemoglobin (HGB), platelet (PLT), FC, high-sensitivity C-reactive protein (hsCRP), erythrocyte sedimentation rate (ESR) and so on], and endoscopic results. FC levels were measured by latex-enhanced turbidimetric immunoassay (LETIA). Endoscopic activity was defined as the simplified endoscopic score for Crohn's disease (SES-CD) > 2. Patients were divided into the endoscopically active group and endoscopic remission group according to endoscopic activity, and the differences in clinical data between the two groups were compared. Spearman correlation analysis was used to assess the correlation between FC and endoscopic activity, and receiver operating characteristic (ROC) curve was used to evaluate the predictive efficacy of FC, hsCRP and ESR for endoscopic activity, and the differences were compared.Results:A total of 90 CD patients were enrolled, including 65 males and 25 females with the age of 30 (22, 41) years old and disease course 4.0 (0.5, 8.0) years. Seventy-one patients (78.9%) had ileocolonic disease involvement (L3), and 55 patients (61.1%) were using biologics. Sixty-nine patients in endoscopic active phase were assigned to the endoscopically active group, while the remaining 21 were assigned to the endoscopic remission group. There were no statistically significant differences in general characteristics such as age and gender between the two groups (all P > 0.05). Compared with endoscopic remission group, HGB was significantly lower in the endoscopically active group, while PLT, hsCRP, ESR, and FC were moderataly higher (all P < 0.05). Among the 90 CD patients, FC levels were moderatly correlated with endoscopic activity (ρ = 0.494). ROC curve analysis indicated that the area under the curve for FC in predicting endoscopic activity was 0.836 (95% CI: 0.737-0.935), with a sensitivity of 0.725, specificity of 0.952, and accuracy of 0.778 at the optimal FC cutoff value of 153.8 μg/g. FC outperformed hsCRP and ESR. Conclusion:FC measured by LETIA demonstrates certain efficacy in predicting endoscopic activity in CD and will assist in efficient clinical monitoring of CD patients.
6.Study on Pre-Clinical In-Vitro Test Methods of Unicondylar Knee Prosthesis.
Shu YANG ; Dan HAN ; Wen CUI ; Zhenxian CHEN ; Jinju DING ; Jintao GAO ; Bin LIU
Chinese Journal of Medical Instrumentation 2025;49(1):111-118
Compared with total knee arthroplasty, unicondylar knee replacement has the advantage of preserving the knee tissue structure and motor function to the greatest extent. Pre-clinical in-vitro test is an important tool to evaluate the safety and effectiveness of unicondylar knee prostheses, and it is also a key focus of the product registration process. Through collection, comparison, and analysis of current regulations, technical standards, guidelines, and related research literature, this paper expounds on the relevant research methods for the pre-clinical in-vitrotesting of unicondylar knee prostheses. At the same time, in conjunction with current evaluation requirements and experience, the study discusses the focus of pre-clinical performance research for unicondylar knee prostheses during the registration process to clarify the performance evaluation requirements of this product category. This aims to provide a reference for the pre-clinical performance research of unicondylar knee prostheses and to standardize industry testing standards.
Knee Prosthesis
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Arthroplasty, Replacement, Knee
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Humans
;
Prosthesis Design
;
Materials Testing
7.Effectiveness of Lianhua Qingwen Granule and Jingyin Gubiao Prescription in Omicron BA.2 Infection and Hospitalization: A Real-World Study of 56,244 Cases in Shanghai, China.
Yu-Jie ZHANG ; Guo-Jian LIU ; Han ZHANG ; Chen LIU ; Zhi-Qiang CHEN ; Ji-Shu XIAN ; Da-Li SONG ; Zhi LIU ; Xue YANG ; Ju WANG ; Zhe ZHANG ; Lu-Ying ZHANG ; Hua FENG ; Yan-Qi ZHANG ; Liang TAN
Chinese journal of integrative medicine 2025;31(1):11-18
OBJECTIVE:
To examine the effectiveness of Chinese medicine (CM) Lianhua Qingwen Granule (LHQW) and Jingyin Gubiao Prescription (JYGB) in asymptomatic or mild patients with Omicron infection in the shelter hospital.
METHODS:
This single-center retrospective cohort study was conducted in the largest shelter hospital in Shanghai, China, from April 10, 2022 to May 30, 2022. A total of 56,244 asymptomatic and mild Omicron cases were included and divided into 4 groups, i.e., non-administration group (23,702 cases), LHQW group (11,576 cases), JYGB group (12,112 cases), and dual combination of LHQW and JYGB group (8,854 cases). The length of stay (LOS) in the hospital was used to assess the effectiveness of LHQW and JYGB treatment on Omicron infection.
RESULTS:
Patients aged 41-60 years, with nadir threshold cycle (CT) value of N gene <25, or those fully vaccinated preferred to receive CM therapy. Before or after propensity score matching (PSM), the multiple linear regression showed that LHQW and JYGB treatment were independent influence factors of LOS (both P<0.001). After PSM, there were significant differences in LOS between the LHQW/JYGB combination and the other groups (P<0.01). The results of factorial design ANOVA proved that the LHQW/JYGB combination therapy synergistically shortened LOS (P=0.032).
CONCLUSIONS
Patients with a nadir CT value <25 were more likely to accept CM. The LHQW/JYGB combination therapy could shorten the LOS of Omicron-infected individuals in an isolated environment.
Humans
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Drugs, Chinese Herbal/therapeutic use*
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Male
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Female
;
Middle Aged
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Adult
;
China/epidemiology*
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Hospitalization
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COVID-19 Drug Treatment
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COVID-19/epidemiology*
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SARS-CoV-2
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Retrospective Studies
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Treatment Outcome
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Length of Stay
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Young Adult
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Aged
8.Erratum: Author correction to "PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism" Acta Pharm Sin B 13 (2023) 157-173.
Mingming SUN ; Leilei LI ; Yujia NIU ; Yingzhi WANG ; Qi YAN ; Fei XIE ; Yaya QIAO ; Jiaqi SONG ; Huanran SUN ; Zhen LI ; Sizhen LAI ; Hongkai CHANG ; Han ZHANG ; Jiyan WANG ; Chenxin YANG ; Huifang ZHAO ; Junzhen TAN ; Yanping LI ; Shuangping LIU ; Bin LU ; Min LIU ; Guangyao KONG ; Yujun ZHAO ; Chunze ZHANG ; Shu-Hai LIN ; Cheng LUO ; Shuai ZHANG ; Changliang SHAN
Acta Pharmaceutica Sinica B 2025;15(4):2297-2299
[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].
9.Five-year outcomes of metabolic surgery in Chinese subjects with type 2 diabetes.
Yuqian BAO ; Hui LIANG ; Pin ZHANG ; Cunchuan WANG ; Tao JIANG ; Nengwei ZHANG ; Jiangfan ZHU ; Haoyong YU ; Junfeng HAN ; Yinfang TU ; Shibo LIN ; Hongwei ZHANG ; Wah YANG ; Jingge YANG ; Shu CHEN ; Qing FAN ; Yingzhang MA ; Chiye MA ; Jason R WAGGONER ; Allison L TOKARSKI ; Linda LIN ; Natalie C EDWARDS ; Tengfei YANG ; Rongrong ZHANG ; Weiping JIA
Chinese Medical Journal 2025;138(4):493-495
10.Buzhong Yiqi Decoction alleviates immune injury of autoimmune thyroiditis in NOD.H-2~(h4)mice via c GAS-STING signaling pathway.
Yi-Ran CHEN ; Lan-Ting WANG ; Qing-Yang LIU ; Zhao-Han ZHAI ; Shou-Xin JU ; Xue-Ying CHEN ; Zi-Yu LIU ; Xiao YANG ; Tian-Shu GAO ; Zhi-Min WANG
China Journal of Chinese Materia Medica 2025;50(7):1872-1880
This study aims to explore the effects of Buzhong Yiqi Decoction(BYD) on the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING) signaling pathway in the mouse model of autoimmune thyroiditis(AIT) and the mechanism of BYD in alleviating the immune injury. Forty-eight NOD.H-2~(h4) mice were assigned into normal, model, low-, medium-, and high-dose BYD, and selenium yeast tablets groups(n=8). Mice of 8 weeks old were treated with 0.05% sodium iodide solution for 8 weeks for the modeling of AIT and then administrated with corresponding drugs by gavage for 8 weeks before sampling. High performance liquid chromatography was employed to measure the astragaloside Ⅳ content in BYD. Hematoxylin-eosin staining was employed to observe the pathological changes in the mouse thyroid tissue. Enzyme-linked immunosorbent assay was employed to measure the serum levels of thyroid peroxidase antibody(TPO-Ab), thyroglobulin antibody(TgAb), and interferon-γ(IFN-γ). Flow cytometry was employed to detect the distribution of T cell subsets in the spleen. The immunohistochemical method was used to detect the expression of cGAS, STING, TANK-binding kinase 1(TBK1), and interferon regulatory factor 3(IRF3). Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of markers related to the cGAS-STING signaling pathway in the thyroid tissue. The results showed that the content of astragaloside Ⅳ in BYD was(7.06±0.08) mg·mL~(-1). Compared with the normal group, the model group showed disrupted structures of thyroid follicular epithelial cells, massive infiltration of lymphocytes, and elevated levels of TgAb and TPO-Ab. Compared with the model group, the four treatment groups showed intact epithelial cells, reduced lymphocyte infiltration, and lowered levels of TgAb and TPO-Ab. Compared with the normal group, the model group showed increases in the proportions of Th1 and Th17 cells, a decrease in the proportion of Th2 cells, and an increase in the IFN-γ level. Compared with the model group, the four treatment groups presented decreased proportions of Th1 and Th17 cells and lowered levels of IFN-γ, and the medium-dose BYD group showed an increase in the proportion of Th2 cells. Compared with the normal group, the modeling up-regulated the mRNA levels of cGAS, STING, TBK1, and IRF3 and the protein levels of cGAS, p-STING, p-TBK1, and p-IRF3. Compared with the model group, the four treatment groups showed reduced levels of cGAS, STING, TBK1, and IRF3-positive products, down-regulated mRNA levels of cGAS, STING, and TBK1, and down-regulated protein levels of cGAS and p-STING. The high-dose BYD group showed down-regulations in the mRNA level of IRF3 and the protein levels of p-TBK1 and p-IRF3. The above results indicate that BYD can repair the imbalance of T cell subsets, alleviate immune injury, and reduce thyroid lymphocyte infiltration in AIT mice by inhibiting the cGAS-STING signaling pathway.
Animals
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Drugs, Chinese Herbal/administration & dosage*
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Signal Transduction/drug effects*
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Thyroiditis, Autoimmune/metabolism*
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Mice
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Membrane Proteins/metabolism*
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Mice, Inbred NOD
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Humans
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Female
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Nucleotidyltransferases/metabolism*
;
Male
;
Disease Models, Animal

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