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.

Purpose: We used bioinformatics methods and Mendelian randomization (MR) analysis to investigate the hub genes involved in acute myeloid leukemia (AML) and their causal relationship with hemolysis, to explore a new direction for molecular biology research of AML. Methods: We first differentially analyzed peripheral blood samples from 62 healthy volunteers and 65 patients with AML from the Gene Expression Omnibus database to obtain differentially expressed genes (DEGs), and intersected them with genes sourced from weighted gene co-expression network analysis (WGCNA) and the GeneCards database to obtain target genes. Target genes were screened using protein–protein interaction (PPI) network analysis and ROC curves to identify genes associated with AML. Finally, we analyzed the correlation between genes and immune cells and the relationship between toll-like receptor 4 (TLR4) and AML using MR. Results: We compared peripheral blood expression profiles using an array of 62 healthy volunteers (GSE164191) and 65 patients with AML (GSE89565) (M0:25; M1:11; M2:10; M3:1; M4:7; M4 eo t [16;16] ou inv [16]:4; M5:6; M6:1) and obtained 7,339 DEGs (3,733 upregulated and 3,606 downregulated). We intersected these DEGs with 4,724 genes from WGCNA and 1,330 genes related to hemolysis that were identified in the GeneCards database to obtain 190 target genes. After further screening these genes using the PPI network, we identified TLR4, PTPRC, FCGR3B, STAT1, and APOE, which are closely associated with hemolysis in patients with AML. Finally, we found a causal relationship between TLR4 and AML occurrence using MR analysis (p < 0.05). Conclusion We constructed a WGCNA-based co-expression network and identified hemolysis-associated AML genes.

OBJECTIVE: miR-34c-3p is down-regulated in nasopharyngeal carcinoma (NPC). The biological role of miR-34c-3p in NPC and its underlying mechanisms are unknown and were explored in this study. METHODS: Flow cytometry and immunohistochemical staining were employed to detect cluster of differentiation 86 (CD86) and cluster of differentiation 206 (CD206) expression; quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were employed to examine mRNA expression and protein levels; cell counting kit-8 (CCK8) and transwell assays were employed to assess cell proliferation, migration, and invasion; and hematoxylin-eosin (HE) staining was employed to assess pathological changes in tumor tissues. RESULTS: Our results revealed that the miR-34c-3p mimic markedly inhibited M2 polarization of macrophages by targeting SLC7A11, and M2 macrophages transfected with the miR-34c-3p mimic inhibited the proliferation, migration, and invasion of NPC cells. The in vivo experiments further confirmed that miR-34c-3p mimics blocked tumor growth and reduced inflammatory infiltration in tumor tissues. CONCLUSION This study provides novel insights into the pathogenesis of NPC and a new treatment strategy.
MicroRNAs/metabolism* ; Nasopharyngeal Carcinoma/genetics* ; Humans ; Animals ; Nasopharyngeal Neoplasms/genetics* ; Macrophages/physiology* ; Cell Line, Tumor ; Mice ; Cell Proliferation ; Mice, Inbred BALB C ; Cell Movement ; Male ; Gene Expression Regulation, Neoplastic ; Mice, Nude ; Female

Purpose: We used bioinformatics methods and Mendelian randomization (MR) analysis to investigate the hub genes involved in acute myeloid leukemia (AML) and their causal relationship with hemolysis, to explore a new direction for molecular biology research of AML. Methods: We first differentially analyzed peripheral blood samples from 62 healthy volunteers and 65 patients with AML from the Gene Expression Omnibus database to obtain differentially expressed genes (DEGs), and intersected them with genes sourced from weighted gene co-expression network analysis (WGCNA) and the GeneCards database to obtain target genes. Target genes were screened using protein–protein interaction (PPI) network analysis and ROC curves to identify genes associated with AML. Finally, we analyzed the correlation between genes and immune cells and the relationship between toll-like receptor 4 (TLR4) and AML using MR. Results: We compared peripheral blood expression profiles using an array of 62 healthy volunteers (GSE164191) and 65 patients with AML (GSE89565) (M0:25; M1:11; M2:10; M3:1; M4:7; M4 eo t [16;16] ou inv [16]:4; M5:6; M6:1) and obtained 7,339 DEGs (3,733 upregulated and 3,606 downregulated). We intersected these DEGs with 4,724 genes from WGCNA and 1,330 genes related to hemolysis that were identified in the GeneCards database to obtain 190 target genes. After further screening these genes using the PPI network, we identified TLR4, PTPRC, FCGR3B, STAT1, and APOE, which are closely associated with hemolysis in patients with AML. Finally, we found a causal relationship between TLR4 and AML occurrence using MR analysis (p < 0.05). Conclusion We constructed a WGCNA-based co-expression network and identified hemolysis-associated AML genes.

Objective:To investigate the effects of 10° head up tilt bed rest (HUT) on human cardiac function via 3D speckle tracking echocardiography (3D-STE), and to study the difference in cardiac function under the submaximal exercise load between the horizontal position and 10° HUBR.Methods:Thirty young healthy volunteers were recruited as the subjects, who were randomly divided into an 10° HUT exercise group and horizontal exercise group with 15 subjects in each. Subjects in both groups were asked to ride the bicycle ergometer in the 10° HUBR position and supine position respectively. The load started with 50 W and was increased by 25 W every 3 min until it reached the maximum of 125 W. Before the exercise (resting state), 1 min after the load was increased each time, and 3 min after exercise (recovery period), the following indices were collected: ①basic cardiac function indices: heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP), ②conventional cardiac ultrasound indices: left ventricular ejection fraction (LVEF), stroke volume (SV) and cardiac output (CO), ③left ventricular strain indices: global longitudinal strain (GLS), global circumferential strain (GCS), and global area strain (GAS) measured by 3D-SET. The changes of these indices in the 2 groups of subjects under different exercise loads were observed.Results:The differences in the major effect of the basic heart indices (HR, SBP and DBP), conventional cardiac ultrasound indices (LVEF, SV and CO) and left ventricular strain indices (GLS, GCS and GAS) in response to the exercise load were statistically significant ( F=194.90, 113.66, 17.19, P=0.017, 0.018, 0.001). With the increase of the exercise load, the basic heart indices and conventional cardiac ultrasound indices kept rising, the left ventricular strain indices reached the minimum under a moderate exercise load (75 W), HR, SBP and CO were higher than those of the resting state ( P<0.05 or 0.01). Both LVEF under exercise loads of 75, 100, 125 W and during recovery, and SV under exercise loads of 100, 125 W and during recovery were significantly higher than those of the resting state ( P<0.05 or 0.01), while GLS and GCS under exercise loads of 50, 75, 125 W ( P<0.05 or 0.01), and GAS under exercise loads of 50, 75 W ( P<0.01) were significantly lower. There were statistically significant differences not only in GCS across the groups ( F=4.60, P=0.026) but also in DBP due to the interactions between the grouping and exercise loads ( F=3.13, P=0.031). DBP was higher than that of the resting state when the exercise load was 125 W in both groups. Conclusions:During submaximal exercise, myocardial contractility shows sustained enhancement with the increase of the exercise load. The results of GLS, GCS and GAS indicate that myocardial strain reaches its lowest value under a moderate exercise load, suggesting that moderate exercise can be used to evaluate cardiac function via 3D-SET. Under a simulated lunar gravity of 10° HUT, there is less deformation in the short axis direction of the myocardium, indicating that GCS can be used as a sensitive indicator to detect changes in cardiac function under different gravities.

Objective To analyze and compare the efficacy of DNA barcode,i.e.,Cytochrome b(Cytb)and 12S ribosomal RNA(12S rRNA)gene sequences,in the species identification of wildlife.Methods DNA extraction,quantification,PCR amplification of Cytb and 12S rRNA gene fragments,Sanger sequencing,and sequence alignment analysis were performed on ten wildlife samples.Results Both gene fragments were successfully amplified in six samples,while Cytb alone was successfully amplified in 1 sample,and 12S rRNA alone in 3 samples.Sequence analysis indicated that Cytb enabled species-level identification for 6 samples(Gallinula chloropus,Streptopelia orientalis,Phasianus colchicus,Falco naumanni,Myiopsitta monachus and Lynx lynx)and genus-level identification for 1 sample(Lepus).In contrast,12S rRNA achieved species-level identificaggion for 8 samples(Gallinula chloropus,Lepus sinensis,Phasianus colchicus,Myiopsitta monachus,Muntiacus reevesi,Macaca mulatta and Lynx lynx),representing seven species,and genus-level identification for 1 sample(Falco).However,by combining Cytb and 12S rRNA,all samples could be identified to the species level.Conclusion When applying DNA barcodes to wildlife identification,the Cytb and 12S rRNA gene regions analyzed here can effectively identify common species such as Gallinula chloropus and Streptopelia orientalis,but face difficulties in distinguishing closely related species within the same genus.Therefore,when conducting wildlife species identification,it is recommended to use two or more DNA barcode markers.

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.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

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.