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.

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.

Objective To investigate the prognostic value of the platelet-to-lymphocyte ratio(PLR)at different early time points in adult patients undergoing veno-arterial extracorporeal membrane oxygenation(VA-ECMO).Methods A retrospective study was conducted,selecting 55 adult patients who underwent VA-ECMO treatment at the First Hospital of Jiaxing from June 2020 to October 2022 as the study subjects.Then,the patients'gender,age,past history[including hypertension,diabetes,heart disease,chronic obstructive pulmonary disease(COPD)],and the reason for extracorporeal membrane pulmonary oxygenation(ECMO)adjuvant therapy[including severe myocarditis,acute myocardia infarction,in-hospital and out-of-hospital cardiac arrest,severe closed craniocerebral injury,severe pneumonia,pelvic fracture,other(pulmonary embolism,electrocution,traumatic hepatic rupture,post-partum hemorrhage,severe acute pancreatitis,crush syndrome)],acute physiology and chronic health evaluationⅡ(APACHEⅡ),sequential organ failure assessment(SOFA)at the time of admission,and ECMO peripheral blood tests[creatinine,alanine aminotransferase(ALT),aspartate aminotransferase(AST),blood lactate acid(Lac),white blood cell count(WBC),neutrophil count(NEU),lymphocyte count(LYM),hemoglobin(Hb),and platelet count(PLT)]and the last time prior to ECMO assistance,24 hours prior to the occurrence of acute kidney injury(AKI),and 24 hours after the occurrence of AKI.PLR levels at 24 hours ECMO,and the proportion of continuous renal replacement therapy(CRRT).The patients were divided into a death group and a survival group based on their 30-day prognosis and further categorized into a CRRT group and a non-CRRT group based on whether CRRT was administered.Clinical indicators of patients with different prognosis and the differences in PLR levels between CRRT and non-CRRT groups were compared.Logistic regression analysis was used to identify independent risk factors affecting the 30-day prognosis of VA-ECMO patients.The receiver operator characteristic(ROC curves)were plotted to evaluate the prognostic predictive value of each risk factor.Results Compared to the survival group,the death group had significantly higher APACHEⅡscores,SOFA scores,LYM and proportion receiving CRRT[APACHEⅡscore:34.00(28.50,36.00)vs.25.00(14.75,34.00),SOFA score:5.00(4.00,6.50)vs.3.00(2.00,5.25),LYM(×109/L):3.40±1.97 vs.2.24±2.11,proportion receiving CRRT:91.30%(21/23)vs.62.50%(20/32)],and a significantly lower level of the last PLR prior to ECMO adjuvant[30.00(21.06,48.17)vs.58.82(41.80,145.72)],and the differences were statistically significant(all P<0.05).Logistic regression analysis showed that the levels of the last PLR before ECMO assistance[odds ratio(OR)=0.965,95%confidence interval(95%CI)was 0.938-0.993,P=0.013],APACHEⅡscore at the time of admission(OR=1.121,95%CI was 1.018-1.234,P=0.020),and CRRT(OR=7.734,95%CI was 1.042-57.401,P=0.045)were independent risk factors affecting the prognosis of the VA-ECMO patients at 30 days after adjuvant;the ROC curve analysis showed that APACHEⅡscore,CRRT and the last PLR level before ECMO assistance had a predictive value for the prognosis of VA-ECMO patients 30 days after assistance,in which the APACHEⅡscore+the last PLR level before ECMO assistance had the greatest predictive value in predicting the prognosis of the patients,with area under the curve(AUC)of 0.846,with a sensitivity of 62.5%and a specificity of 95.7%.Higher early PLR levels were associated with better prognosis.In the CRRT group,PLR levels at 24 hours before ECMO initiation,24 hours before AKI onset,and 24 hours after AKI onset were significantly lower than those in the non-CRRT group(all P<0.05).Conclusion Early PLR levels and CRRT administration have significant predictive value for the prognosis of patients undergoing VA-ECMO therapy.

Objective To comparatively analyze the clinical characteristics of primary bilateral macronodular adrenal hyperplasia(PBMAH)and adrenal cortisol-producing Adenoma(CPA),and enhance the understanding of two diseases.Methods The clinical data of 85 PBMAH patients(PBMAH group)and 195 CPA patients(CPA group)diagnosed at Department of Endocrinology,the First Medical Center of Chinese PLA General Hospital,from September 2014 to August 2024 were retrospectively analyzed.The demographic characteristics,comorbidities,biochemical indicators,adrenocorticotropic hormone-cortisol(ACTH-F)levels,and adrenal imaging features and treatment conditions were compared between the two groups.Results(1)General characteristics:Compared with CPA group,PBMAH group had older age at diagnosis and a higher proportion of male patients.(2)Clinical characteristics:Compared with CPA group,PBMAH group had a longer disease duration,a higher proportion of subclinical Cushing's syndrome(CS),and a higher proportion of hypertension,impaired glucose tolerance/diabetes,bone mass reduction or osteoporosis,with higher serum potassium levels,and the differences were statistically significant(P<0.01).(3)Hormone levels:Both PBMAH and CPA groups showed ACTH-F rhythm disorder,significantly increased cortisol levels and suppressed ACTH.Compared with PBMAH group,CPA group had stronger autonomous cortisol secretion ability,manifested by increased midnight serum cortisol(F0:00),16:00 serum cortisol(F16:00),24-hour urinary free cortisol(24 h UFC)levels and lower 8:00 serum ACTH(ACTH8:00)and 16:00 serum ACTH(ACTH16:00)(P<0.01).After low-dose dexamethasone suppression test(LDDST),CPA group showed lower suppression rates of ACTH and cortisol,and higher proportions of paradoxical elevation in serum cortisol and 24 h UFC compared with PBMAH(P<0.01).Conclusions PBMAH has a longer disease course and higher proportions of comorbid metabolic disorders than CPA,mostly manifested as subclinical Cushing's syndrome.CPA has stronger autonomous cortisol secretion ability,with cortisol less likely to be suppressed after LDDST and more obvious paradoxical elevation of cortisol and 24 h UFC.

Objective To characterize multimodal metabolic disorders in subclinical Cushing's syndrome(SCS)patients with different cortisol levels,providing a reference for clinical diagnosis and treatment.Methods A retrospective analysis was conducted on the clinical data of 165 SCS patients diagnosed at the First Medical Center of Chinese PLA General Hospital due to adrenal masses from January 2014 to October 2024.Using the serum cortisol levels after the midnight 1 mg dexamethasone suppression test(1 mg DST)as the cut-off point,SCS patients were divided into high-level group(1 mg DST-F>138 nmol/L,n=96)and low-level group(50 nmol/L<1 mg DST-F≤138 nmol/L,n=69).The differences in age,gender,body mass index(BMI),blood pressure,glucolipid metabolism indices,electrolytes,hormone levels,and imaging features of adrenal adenoma(such as CT values)were compared between the two groups.Multivariate linear regression was used to analyze the correlation between CT values and metabolic indices.Results Compared with low-level group,patients in high-level group were younger(54.0±11.3 vs.57.7±10.3,P=0.034),while there were no statistically significant differences in gender ratio or BMI between the two groups(P>0.05).Both groups exhibited decreased adrenocorticotropic hormone(ACTH)levels and disrupted circadian rhythm.Compared with low-level group,high-level group showed significantly higher F0:00 levels[250.00(170.07,422.53)nmol/L vs.110.00(82.74,133.90)nmol/L]and 24-hour urinary free cortisol(24 h UFC)[568.40(377.80,875.45)nmol/24 h vs.369.40(265.40,494.69)nmol/24 h](P<0.001),with no significant differences in serum F8:00,or 1 mg DST ACTH0:00 levels(P>0.05).Except for the fasting C-peptide level in the high-level group being higher than that in low-level group[(2.88±1.01)ng/ml vs.(2.46±0.78)ng/ml,P=0.024],there were no significant differences in blood pressure,blood lipids,glycated hemoglobin(HbA1c),fasting blood glucose,fasting insulin,serum electrolytes,uric acid,and other indices between the two groups(P>0.05).The CT value of adrenal adenoma during contrast-enhanced scanning was higher in high-level group[80.00(17.80,93.00)Hu vs.52.00(35.50,75.00)Hu,P=0.006]compared with low-level group.Multivariate linear regression analysis revealed that diastolic blood pressure was positively correlated with CT values of adrenal adenomas in both plain scanning(β=0.49,95%CI 0.09-0.90)and contrast-enhanced scanning(β=2.08,95%CI 0.76-3.39),while triglyceride levels were negatively correlated with plain scanning CT values(β=-5.77,95%CI-10.88--0.66).Conclusion Patients with SCS at different cortisol levels differ in age,fasting C-peptide levels,and CT values.CT values may serve as potential imaging markers to assess metabolic risk in SCS patients.

Objective To investigate the clinical characteristics of patients with clinical and subclinical Cushing's syndrome caused by primary bilateral macronodular adrenal hyperplasia(PBMAH).Methods A retrospective analysis was performed on the clinical data of 198 patients with Cushing's syndrome caused by PBMAH diagnosed in the First Medical Center of Chinese PLA General Hospital from January 2004 to October 2024.According to clinical manifestations,the patients were classified into clinical type Cushing's syndrome(n=61)and subclinical type Cushing's syndrome(n=137),and the clinical characteristics of the two types were compared.Results The mean age at diagnosis of patients with PBMAH-induced Cushing's syndrome was(53.5±10.4)years,including 118 males and 80 females,with a male-to-female ratio of 1.475:1.Compared with the subclinical type,the clinical type had a higher proportion of females,higher levels of serum cortisol,24-hour urine free cortisol(24 h UFC),and inhibited serum cortisol after low-dose dexamethasone suppression.Additionally,the clinical type had lower plasma ACTH,larger adrenal nodules and a higher risk of surgery(P<0.05)compared with those in subclinical type.The incidences of hypertension,dyslipidemia,obesity,diabetes mellitus,hypokalemia,vitamin D deficiency,osteoporosis,coronary heart disease,and cerebrovascular disease in patients with Cushing's syndrome caused by PBMAH were 87.9%,50.5%,37.1%,36.9%,27.8%,25.9%,18.7%,18.7%and 12.1%,respectively.Among them,compared with subclinical type patients,clinical type patients had higher incidence of hypokalaemia,vitamin D deficiency and osteoporosis(P<0.05),while there were no statistically significant differences in the incidences of other comorbidities between the two types(P>0.05).The results of postoperative follow-up for PBMAH patients showed that the short-term biochemical remission rate of unilateral total adrenalectomy was 41.5%(22/53)and the long-term biochemical remission rate was 32.0%(8/25).The short-term biochemical remission rate of unilateral partial(or nodular)adrenalectomy was 52.9%(9/17),and the long-term biochemical remission rate was 14.3%(1/7).All patients who underwent unilateral total adrenalectomy plus contralateral partial resection developed adrenal insufficiency(3/3),and 1 patient(1/3)relapsed 3.4 years after surgery.Conclusion Clinical and subclinical types of Cushing's syndrome caused by PBMAH have their distinct clinical characteristics.Surgery is an effective treatment for PBMAH,but a certain proportion of patients fail to achieve biochemical remission after non-bilateral total adrenalectomy.

Objective To analyze the clinical characteristics,treatment,and prognosis of immune checkpoint inhibitor-related diabetes mellitus(ICI-DM).Methods The clinical characteristics,laboratory examinations,treatment regimens,and follow-up outcomes of 10 ICI-DM patients who were diagnosed and treated in the First Medical Center of Chinese PLA General Hospital between July 2019 and December 2024 were retrospectively analyzed.Relevant literatures were retrieved from domestic and foreign databases such as PubMed,CNKI,and VIP.The clinical characteristics of ICI-DM were summarized based on the literature results.Results All 10 patients were PD-1 inhibitor users,including 5 males and 5 females,with a median age of 54.5(51.3,64.0)years and a body mass index(BMI)of(22.0±2.15)kg/m2.Among them,9 cases(90.0%)were fulminant type 1 diabetes mellitus(FT1DM);9 cases(90.0%)had a severity of adverse events reaching grade 3-4 according to the Common Terminology Criteria for adverse events(CTCAE).The median time from PD-1 inhibitor treatment to the occurrence of the classic diabetes symptoms referred to as"three more and one less"(polyuria,polydipsia,polyphagia,and weight loss)in all patients was 145.5(110.5,204.8)days,and the medication duration was 6.0(4.3,7.8)cycles.The average blood glucose level of the 10 patients at the time of consultation was 25.3(10.0-41.4)mmol/L,and the glycated hemoglobin(HbA1c)level was 8.0%(6.6%-10.9%).Eight patients had fasting and 2-hour C-peptide levels<0.1 ng/ml(fasting C-peptide from<0.010 to 0.067 ng/ml,2-hour C-peptide from<0.010 to 0.077 ng/ml).Nine of the 10 patients were negative for diabetes autoantibodies,while 1 was not tested.All 10 patients were successfully treated with insulin and other therapies.During the follow-up after discharge,all patients still relied on insulin treatment,and no significant recovery of pancreatic islet β cell function was observed compared with that at discharge.Literature review revealed that ICI-DM was more common in PD-1 inhibitor users,with clinical mainly manifested as diabetic ketoacidosis(DKA)(65.4%)and diabetic ketosis(13.1%).Patients had severely impaired pancreatic islet function and required long-term insulin treatment,and some cases were complicated by thyroid or pituitary dysfunction.Conclusions ICI-DM typically presents as FT1DM,often manifesting with DKA or diabetic ketosis at onset.It is characterized by severe and irreversible loss of pancreatic islet function,necessitating lifelong insulin therapy.To enable early detection and prompt treatment,close monitoring of blood glucose is essential during ICI treatment.

Objective To propose a high-precision deep learning-based image assessment method of osteosarcoma chemotherapy efficacy for clinical treatment,as existing methos have low accuracy of osteosarcoma assessment.Methods The low incidence of osteosarcoma led to the small scale of its imaging data and the problem of imbalance in data categories.This study combined deep learning with clinical medical information,combined the bone sarcoma generation module of BoneGAN and the scale lesion information capture module,and proposed OMLA-Net,a deep learning assessment network for chemotherapy effect of bone sarcoma based on multi-scale lesion attention network,which achieved computer-aided bone tumor assessment with integrated data augmentation and focused lesion information through pre-training and generalized loss training.Results In this study,40 cases of osteosarcoma MRI data were used as the basis for the comparison test on the generated dataset,and the OMLA-Net assessment outperformed the SOTA method Conv-LSTM-GAN in terms of the assessment effects such as accuracy and F1 scores,and the difference was statistically significant(Bootstrap statistical method P＜0.05);the subsequent K-fold cross-validation ablation experiments further demonstrated the effectiveness of each module proposed by OMLA-Net.Conclusion OMLA-Net can effectively perform the impact assessment of chemotherapy effect on osteosarcoma,which provides a new idea for subsequent clinical application.

Guided by the pathogenesis of"structure-activity imbalance of lung collaterals",this paper proposes that structure-activity imbalance of lung collaterals is the initial factor of idiopathic pulmonary fibrosis(IPF)and elucidates the pathogenesis of abnormal changes in biomechanical properties of IPF.It is postulated that the changes of biomechanical properties of lung tissue are closely related to the injury of lung qi collaterals,the abnormal mechanical stress are closely related to the injury of lung blood collaterals,and the biomechanical response of intrapulmonary resident cells is closely related to the structure-activity imbalance of lung collaterals,which ultimately leading to abnormal increase in lung tissue stiffness and progressive scarring formation in lung tissue.Integrating traditional pathogenesis concepts with microscopic pathological changes,and the in-depth exploration of the correlation between the structure-activity imbalance of lung collaterals and the biomechanical properties of IPF can provide direction for exploring IPF medical-engineering cross research,which are of great significance for enriching the syndrome and treatment system of lung collateral diseases.

BACKGROUND:When exercising in a cold environment,the body's inflammatory response is affected by both low temperature and exercise intervention,and its impact and mechanism remain to be explored.OBJECTIVE:To explore the effects and mechanisms of cold water swimming on inflammatory response of rats based on transcriptome sequencing technology.METHODS:40 male SD rats were randomly divided into room temperature control group,room temperature swimming group,cold water control group,and cold water swimming group,with 10 rats in each group.The room temperature control group had no intervention and was free to eat.The room temperature swimming group received swimming at 30 min/time,6 times/week,for 5 weeks;the water temperature was(28±2)℃,and the water depth was 35 cm.In the cold water control group,the rats were placed in a water tank with a depth of 3 cm;the water temperature was(18±2)℃,and they were free to move.The cold water swimming group received swimming at 30 min/time,6 times/week,for 5 weeks;the water temperature was(18±2)℃,and the water depth was 35 cm.Enzyme-linked immunosorbent assay was used to detect the levels of serum interleukin-6,tumor necrosis factor-α,and high-sensitivity C-reactive protein.Based on the transcriptome sequencing results,differentially expressed genes were screened to draw Venn diagrams and heat maps,and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed.The protein-protein interaction network was used to screen core genes.RT-qPCR was used to detect the mRNA expression of IRF7,OAS2,and OASL in rat spleen tissue.RESULTS AND CONCLUSION:(1)The ELISA results showed that compared with the room temperature control group,the levels of various inflammatory indicators in the room temperature swimming group and the cold water swimming group were significantly increased(P＜0.05),and there was no significant difference in the cold water control group.Compared with the room temperature swimming group,there was no significant difference in the expression of inflammatory indicators in the cold water swimming group.Compared with the cold water control group,the expressions of interleukin-6 and tumor necrosis factor-α in the cold water swimming group showed an upward trend,and high-sensitivity C-reactive protein increased significantly(P＜0.05).(2)Transcriptome analysis:Venn diagram showed that there were 39 differentially expressed genes affected by the dual factors of temperature and exercise intervention.Cluster heat map analysis results showed that the overall gene expression trends of the room temperature swimming group and the cold water swimming group were similar,and the cold water control group showed an opposite trend.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis results showed that differentially expressed genes were enriched in the immune system,locomotion,nucleic acid-binding transcription factor activity,NOD-like receptor signaling pathways and other pathways.The number of genes enriched in the NOD-like receptor signaling pathway was relatively large,and the q value was small,which may be a key pathway.The protein-protein interaction network screened out IRF7,OAS2,OASL,IFIT2,IFIT3 and other core genes.(3)RT-qPCR verification results showed that compared with the room temperature control group,the expressions of IRF7,OAS2 and OASL were significantly increased in the room temperature swimming group and the cold water swimming group(P＜0.01),and there was no significant difference in the cold water control group.Compared with the cold water control group,the expression of each gene was significantly increased in the cold water swimming group(P＜0.01).(4)It is concluded that cold water swimming can promote inflammatory response,and its mechanism may be regulated through the NOD-like receptor signaling pathway.