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.

Anti-tumor traditional Chinese medicine has a long history of clinic application, in which the star molecules have always been the hotspot of modern drug research, but they are limited by the solubility, stability, targeting, bioactivity or toxicity of the monomer components of traditional Chinese medicine anti-tumor star molecules and other pharmacokinetic problems, which hinders the traditional Chinese medicine anti-tumor star molecules for further clinical translation and application. Currently, the nanosystems prepared by supramolecular technologies such as molecular self-assembly and nanomaterial encapsulation have broader application prospects in improving the anti-tumor effect of active components of traditional Chinese medicine, which has attracted extensive attention from scholars at home and abroad. In this paper, we systematically review the research progress in preparation of supramolecular nano-systems from anti-tumor star molecule of traditional Chinese medicine, and summarize the two major categories and ten small classes of carrier-free and carrier-based supramolecular nanosystems and their research cases, and the future development direction is put forward. The purpose of this paper is to provide reference for the research and clinical transformation of using supramolecular technology to improve the clinical application of anti-tumor star molecule of traditional Chinese medicine.

Metformin has been used for the treatment of type II diabetes mellitus for decades due to its safety, low cost, and outstanding hypoglycemic effect clinically. The mechanisms underlying these benefits are complex and still not fully understood. Inhibition of mitochondrial respiratory-chain complex I is the most described downstream mechanism of metformin, leading to reduced ATP production and activation of AMP-activated protein kinase (AMPK). Meanwhile, many novel targets of metformin have been gradually discovered. In recent years, multiple pre-clinical and clinical studies are committed to extend the indications of metformin in addition to diabetes. Herein, we summarized the benefits of metformin in four types of diseases, including metabolic associated diseases, cancer, aging and age-related diseases, neurological disorders. We comprehensively discussed the pharmacokinetic properties and the mechanisms of action, treatment strategies, the clinical application, the potential risk of metformin in various diseases. This review provides a brief summary of the benefits and concerns of metformin, aiming to interest scientists to consider and explore the common and specific mechanisms and guiding for the further research. Although there have been countless studies of metformin, longitudinal research in each field is still much warranted.
Humans ; Metformin/pharmacokinetics* ; Diabetes Mellitus, Type 2/metabolism* ; Hypoglycemic Agents/pharmacology* ; AMP-Activated Protein Kinases/metabolism* ; Aging

Pancreatic lipase (PL), a crucial enzyme in the digestive system of mammals, has been proven as a therapeutic target to prevent and treat obesity. The purpose of this study is to evaluate and characterize the PL inhibition activities of the major constituents from Fructus Psoraleae (FP), one of the most frequently used Chinese herbs with lipid-lowering activity. To this end, a total of eleven major constituents isolated from Fructus Psoraleae have been obtained and their inhibition potentials against PL have been assayed by a fluorescence-based assay. Among all tested compounds, isobavachalcone, bavachalcone and corylifol A displayed strong inhibition on PL (IC < 10 μmol·L). Inhibition kinetic analyses demonstrated that isobavachalcone, bavachalcone and corylifol A acted as mixed inhibitors against PL-mediated 4-methylumbelliferyl oleate (4-MUO) hydrolysis, with the K values of 1.61, 3.77 and 10.16 μmol·L, respectively. Furthermore, docking simulations indicated that two chalcones (isobavachalcone and bavachalcone) could interact with the key residues located in the catalytic cavity of PL via hydrogen binding and hydrophobic interactions. Collectively, these finding provided solid evidence to support that Fructus Psoraleae contained bioactive compounds with lipid-lowering effects via targeting PL, and also suggested that the chalcones in Fructus Psoraleae could be used as ideal leading compounds to develop novel PL inhibitors.

Objective To access the effects of different doses of recombinant fusion protein of human tumor necrosis factor receptor mutant and Fc fragment [rhTNFR(m):Fc] after a single subcutaneous injection on the plasma concentration of tumor necrosis factor-α (TNF-or) in Chinese healthy volunteers.Methods A total of 56 healthy Chinese volunteers were randomly divided into 6 groups to receive a single injection of 10,20,35,65,75 mg of rhTNFR(m):Fc.The plasma concentrations of TNF-α and total TNF-α were determined at 1 h pre-dose and at 4,48,96,168,216,264,312,384,480 h post-dose.Results After administration of rhTNFR(m):Fc at 0-264 h,the plasma concentrations of free TNF-α and total TNF-α increased significantly in the each group.At 264-480 h post-dose,the concentration of them began to decrease,and at 480 h the concentration of free TNF-α almostly decreased to normal levels.In the dose range of 10-75 mg,the exposure of free TNF-α and total TNF-α (Cmax) had no significant correlation with the dose of rhTNFR (m):Fc.Conclusion After giving the single dose of rhTNFR (m):Fc,there was an increase of free and total TNF-α plasma concentration in Chinese healthy volunteers.As a result,the plasma concentration of free and total TNF-α may not be a suitable pharmacodynamic evaluation index.

Objective To assess the changes in iodine status and dietary iodine intake among Shanghai residents since common salt was iodized 20 years ago.Methods As-CE Catalysis spectrophotometry was used to determinate the urine iodine level in school-age children,pregnant women,wet nurse and adults of Shanghai between 1995 and 2015.B ultrasonic was used to determinate the thyroid volume of school-age children.And then the goiter rate was calculated.Direct titration or arbitration methods were applied to detect the household salt iodine level quantitatively.The survey was conducted by using 3 days 24-hour dietary questionnaire and condiment weighing methods to analyze the level of iodine intake and sources for the cases of all iodized salt consumption and all consumption of non-iodized salt.Results The median urine iodine concentration (UIC) of school age children was 72.3 μg/L in 1995,rose to 214-231 μg/L from 1997-1999,and then became stable between 100 μg/L and 200 μg/L since 2002.The goiter rate was below 5% among children aged 8-10 from 1995-2015 in Shanghai.The median urine iodine of pregnant women was between 126.5 μg/L and 139.8 μg/L.The median UIC of other populations were all between 100 μg/L and 200 μg/L: with adults,lactating women,infants and young children and women of childbearing age,the median urinary iodine was 138.4,123.1-131.1,150.1 and 125.6 μg/L.The qualified iodized salt at household consumption rate was 90% from 2001 to 2009,the percentage declined year by year from 2010.In the cases of all taking iodine salt,the median iodine intake volume for male aged 7-10,11-13,14-18 and over 18 was 200.3,235.5,252.7 and 215.4 μg/L;women aged 7-10,11-13,14-18 and over 18 was 193.0,213.8,208.3 and 186.1 μg/L.The contribution rate of iodine salt in the diet were 51.6%-54.1% and 49.1%-53% in men and women.Kelp,seaweed and fish and shrimp on the contribution of iodine are 7.6%-16.6% and 4.5%-7.4%.Conclusion In the past about 20 years,iodine nutritional status of residents in Shanghai has stabilized totally in a appropriate and safe level.However,the iodine nutrition of pregnant women was insufficient.As iodized salt is the major source of dietary iodine in coastal areas,it is still necessary to continue the policy of universal salt iodized in Shanghai to ensure residents'' needs for iodine and control the risk of iodine deficiency.

OBJECTIVEThis study was designed to evaluate the prevalence of thyroid nodules (TNs) and its relationship with urine iodine concentrations (UICs) after the regional rapid economic growth and lifestyle changes.

METHODSA cross-sectional survey was conducted in the general population aged 15-69 years. A questionnaire regarding general and personal characteristics and relevant information was administered. Ultrasonography of the thyroid was performed, and serum triiodothyronine (T3), tetraiodothyronine (T4), serum thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free tetraiodothyronine (FT4), thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), and TSH receptor antibody (TRAb) levels were measured for each individual subject.

RESULTSThe prevalence rates of TNs in the whole population, females and males were 27.76%, 34.04%, and 21.60%, respectively. The prevalence of multiple nodules increased with age, whereas the prevalence peaks differed between males and females. The median UICs in the whole population and females with non-TNs were higher than those of subjects with TNs (P=0.0035, P=0.0068). The median UICs in subjects with a single TN were higher than those in subjects with multiple TNs (P=0.0164, P=0.0127). The result showed a U-shaped curve relationship between UIC and prevalence of TNs. The prevalence of TNs was the lowest when the UIC was 140-400 μg/L.

CONCLUSIONThe prevalence of TNs was nearly 30% and increased with age. The relationship between UIC and prevalence of TNs is U-shaped, with an increase in risk when the UIC was <140 μg/L and >400 μg/L. Very low or high UIC levels need attention and correction.

Adolescent ; Adult ; Aged ; China ; epidemiology ; Cross-Sectional Studies ; Female ; Humans ; Iodine ; urine ; Male ; Middle Aged ; Nutritional Status ; Prevalence ; Thyroid Nodule ; chemically induced ; epidemiology ; Young Adult

The fruit of Lycium ruthenicum is a common folk medicine in China. Now it is popular for its antioxidative effect and other medical functions. The adulterants of the herb confuse consumers. In order to identify a new adulterant of L. ruthenicum, a research was performed based on NCBI Nucleotide Database ITS Sequence, combined analysis of the origin and morphology of the adulterant to traceable varieties. Total genomic DNA was isolated from the materials, and nuclear DNA ITS sequences were amplified and sequenced; DNA fragments were collated and matched by using ContingExpress. Similarity identification of BLAST analysis was performed. Besides, the distribution of plant origin and morphology were considered to further identification and verification. Families and genera were identified by molecular identification method. The adulterant was identified as plant belonging to Berberis. Origin analysis narrowed the range of sample identification. Seven different kinds of plants in Berberis were potential sources of the sample. Adulterants variety was traced by morphological analysis. The united molecular identification-origin-morphology research proves to be a preceding way to medical herbs traceability with time-saving and economic advantages and the results showed the new adulterant of L. ruthenicum was B. kaschgarica. The main differences between B. kaschgarica and L. ruthenicum are as follows: in terms of the traits, the surface of B. kaschgarica is smooth and crispy, and that of L. ruthenicum is shrinkage, solid and hard. In microscopic characteristics, epicarp cells of B. aschgarica thickening like a string of beads, stone cells as the rectangle, and the stone cell walls of L. ruthenicum is wavy, obvious grain layer. In molecular sequences, the length of ITS sequence of B. kaschgarica is 606 bp, L. ruthenicum is 654 bp, the similarity of the two sequences is 53.32%.
Berberis ; classification ; cytology ; genetics ; China ; DNA Barcoding, Taxonomic ; methods ; DNA, Plant ; chemistry ; genetics ; DNA, Ribosomal Spacer ; chemistry ; genetics ; Drug Contamination ; Drugs, Chinese Herbal ; isolation & purification ; standards ; Lycium ; classification ; cytology ; genetics ; Medicine, Chinese Traditional ; Phylogeny ; Sequence Analysis, DNA ; Species Specificity

OBJECTIVETo investigate the expression level of SOX11 mRNA in mantle cell lymphoma (MCL) and other B-cell non-Hodgkin lymphoma (B-NHL) and its prognostic value in MCL.

METHODSThe expression level of SOX11 mRNA in 80 B-NHL patients were determined by real-time quantitative RT-PCR, GAPDH was used as internal control. The dispersion of SOX11 expression ratio of groups with different prognostic factors was described by Mann-Whitney U test.

RESULTSThe SOX11 mRNA expression level was 2.90 (0.75 - 4.63) in 80 B-NHL patients, and the expression level was significantly higher in MCL than that in other B-NHL (P = 0.014). The SOX11 expression level was statistically lower in the group of MCL with hyperleukocytosis, 12 trisomy, MYC amplification and therapeutic effect < PR (P = 0.042, 0.013, 0.028, 0.009) than that of MCL in other group. But SOX11 expression was not associated with MCL international prognostic index (MIPI) (P = 0.333), lactate dehydrogenase (LDH) (P = 0.790), ATM mutation (P = 0.865) and P53 deletion (P = 0.116). The progression free survival (PFS) and overall survival (OS) were significantly longer in the MCL patients with high level of SOX11 than that of other MCL patients.

CONCLUSIONThere was statistically significant differences in SOX11 mRNA expression between MCL with other B-NHL. SOX11 maybe a good prognostic factor in MCL.

Adult ; Aged ; Aged, 80 and over ; Female ; Gene Expression ; Humans ; Lymphoma, Mantle-Cell ; genetics ; metabolism ; pathology ; Lymphoma, Non-Hodgkin ; genetics ; pathology ; Male ; Middle Aged ; Prognosis ; RNA, Messenger ; genetics ; SOXC Transcription Factors ; genetics ; metabolism