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.

BACKGROUND:Spleen has the functions of blood storage,hematopoiesis,and immunity.With the increase of age,the structural degeneration and functional decline of spleen lead to the impairment of immune system function,thus accelerating the aging process of the body.The treatment of spleen aging in tree shrews with highly active umbilical cord mesenchymal stem cells has not been reported. OBJECTIVE:To explore the intervention effect and mechanism of highly active umbilical cord mesenchymal stem cells on spleen aging in tree shrews. METHODS:Highly active umbilical cord mesenchymal stem cells were isolated,cultured,and obtained from the umbilical cord tissue of newborn tree shrews by caesarean section.The differentiation abilities of adipogenesis,osteogenesis,and chondrogenesis were detected by three-line differentiation kit.Cell cycle and surface markers were detected by flow cytometry.The second generation of highly active umbilical cord mesenchymal stem cells were transfected with Genechem Green Fluorescent Protein with infection complex values of 100,120,140,160,180,and 200,respectively,to screen the best transfection conditions.After transfection,the fourth generation of highly active umbilical cord mesenchymal stem cells was injected into the tail vein of tree shrews in the elderly treatment group.The young control group and the aged model group were not given special treatment.After 4 months of treatment,the spleen tissue was taken and the structure of the spleen was observed by hematoxylin-eosin staining.β-Galactosidase staining was used to detect the activity of aging-related galactosidase.Immunohistochemical staining was used to detect the expression levels of p21 and p53 proteins.Ki67 and PCNA immunofluorescence staining was used to detect cell proliferation activity.Immunofluorescence staining was used to detect the expression levels of spleen autophagy protein molecules Beclin 1 and APG5L/ATG5.Reactive oxygen species fluorescence staining was used to detect the content of reactive oxygen species in spleen tissue.CD3 immunofluorescence staining was used to detect the change of the proportion of total T lymphocytes.The secretion levels of interleukin 1β and transforming growth factor β1 in spleen were detected by enzyme linked immunosorbent assay.The distribution of highly active umbilical cord mesenchymal stem cells labeled with green fluorescent protein in spleen tissue was observed by DAPI double staining of nucleus. RESULTS AND CONCLUSION:(1)Highly active umbilical cord mesenchymal stem cells grew in a short spindle shape with fish-like growth,with a large proportion of G0/G1 phase,and had the potential to differentiate into adipogenesis,osteogenesis,and chondrogenesis.(2)Multiplicity of infection=140 and transfection for 72 hours were the best conditions for labeling tree shrews highly active umbilical cord mesenchymal stem cells with Genechem Green Fluorescent Protein.(3)Compared with the aged model group,in the aged treatment group,the spleen tissue cells of tree shrews were arranged closely,and the area of white pulp was increased(P<0.01);the boundary between red pulp and white pulp was clear;the proportion of germinal centers did not show statistically significant difference(P>0.05).The activity level of galactosidase related to spleen tissue aging was decreased(P<0.001),and the expression levels of aging protein molecules p21 and p53 were down-regulated(P<0.001).The expression levels of proliferation-related molecules Ki67 and PCNA were up-regulated(P<0.001,P<0.05);expression levels of autophagy-related molecules Beclin 1 and APG5L/ATG5 were up-regulated(P<0.001),and the content of reactive oxygen species decreased(P<0.001),and the proportion of CD3+T cells increased(P<0.05).The secretion level of interleukin 1β in the aging-related secretion phenotype decreased(P<0.001);no significant difference was found in transforming growth factor β1 level(P>0.05).Compared with the young control group,the above indexes were significantly different in the elderly treatment group(P<0.05).(4)Green fluorescent cells labeled with green fluorescent protein were observed in spleen tissue of tree shrews the elderly treatment group by frozen tissue section observation.The results show that intravenous infusion of highly active umbilical cord mesenchymal stem cells can migrate to spleen tissue,inhibit the production of reactive oxygen species,down-regulate the expression of aging-related proteins,induce autophagy,promote cell proliferation,reduce chronic inflammation,and then improve the structure and function of spleen tissue.

Recent years have witnessed significant advancements in myopia control research through the application of diffuse optical technology(DOT)spectacle lenses. Myopia has emerged as a global public health challenge, affecting nearly half of the world's population, with childhood and adolescent myopia rates continuing to rise. DOT lenses represent an innovative myopia control intervention based on retinal contrast signal theory. These lenses incorporate micro-light scattering dots distributed across the lens surface to reduce retinal imaging contrast and modulate the influence of visual input on axial elongation, thereby slowing myopia progression. The core mechanism operates through refractive index differences between the lens substrate(1.53)and scattering dots(1.50), which generate optical scattering effects. This design maintains clear vision through a central 5 mm optical zone while effectively reducing contrast signal intensity in the peripheral retina. Large-scale randomized controlled trials, including the CYPRESS study, have demonstrated significant myopia control efficacy in children aged 6-10 years: 12-month follow-up data revealed a 74% reduction in myopia progression and a 50% reduction in axial elongation, with sustained safety and visual quality maintained over 4-year long-term follow-up. However, several aspects of DOT technology remain contentious and require further clinical validation, including its applicability across different age groups, optimal scattering dot density configurations, combined application effects with other myopia control methods, and long-term visual adaptation during extended use. This review systematically examines the theoretical foundations, design characteristics, clinical application progress, and future development directions of DOT technology, providing scientific evidence for clinical myopia prevention and control strategy formulation.

OBJECTIVE To compare the predictive accuracy and clinical applicability of four vancomycin individualized dosing tools （SmartDose， ClinCalc， Gulou， Pharmado） and provide a basis for rational clinical medication use. METHODS A retrospective cohort study was conducted， enrolling 479 adult patients who received vancomycin therapy and underwent steady-state trough concentration monitoring in Zhongshan Hospital， Fudan University （Xiamen Branch） from January 1， 2022， to June 30， 2024. The predictive accuracy of each tool was evaluated using indicators， such as mean error （ME）, mean absolute error （MAE）， mean percentage error （MPE）， mean absolute percentage error （MAPE）， the proportion of patients with an absolute percentage error （APE） of less than 30%， the 95% limits of agreement， and the overall relative percentage difference between predicted and measured values. Using indicators such as accessibility， patient management， and recommendation of multiple treatment options， the clinical panxso@163.com applicability of the tools for all patients was evaluated； using the discrepancy in accuracy between the predicted and actual measured blood drug concentrations as an indicator， the clinical applicability was assessed for patients in different renal function subgroups （hyperfunction， normal， mild impairment， moderate impairment， and severe impairment）. RESULTS In terms of accuracy， SmartDose demonstrated the best overall performance with an MAPE of 46.40% and a proportion of APE ＜30% （46.56%）. Bland-Altman analysis indicated that SmartDose had the smallest overall relative percentage difference （－7.25%）， although the 95% limits of agreement were broad for all tools， with differences between the upper and lower limits exceeding 200%. In terms of applicability， all four dosing tools were freely accessible and demonstrated good availability； SmartDose and Pharmado provided the most comprehensive solutions， offering features such as patient management， multiple regimen recommendations， and drug concentration-time curve plotting. Stratified analysis based on renal function revealed that Pharmado showed optimal prediction for hyperfiltration patients （mean difference： 0.11 mg/L）. SmartDose and ClinCalc showed relatively better performance in normal and mild renal impaiment （mean difference： 0.37， 0.51 mg/L and －1.13， －1.33 mg/L，respectively）. SmartDose performed best in moderate renal impairment （mean difference： －2.60 mg/L）. Pharmado and Gulou had smaller prediction biases in severe renal impairment （mean differences： 1.52 mg/L and －0.23 mg/L， respectively）. CONCLUSIONS The four individualized dosing tools demonstrated limited accuracy in the initial prediction of vancomycin concentrations. Among them， SmartDose demonstrates the highest overall prediction accuracy and possesses comprehensive clinical management features. It is recommended that Pharmado be preferred for patients with renal hyperfiltration； SmartDose or ClinCalc can be used for patients with normal or mildly impaired renal function； SmartDose is recommended for patients with moderately impaired renal function； Pharmado or Gulou may be considered for patients with severely impaired renal function.

OBJECTIVE: To investigate the clinical efficacy of thoracoscopic minimally invasive surgery with nickel-titanium shape memory alloy wrap bone plate versus rib periosteal internal fixation in patients with multiple rib fractures (MRF) and flail chest. METHODS: A retrospective analysis was performed on 100 patients with MRF and flail chest treated with thoracoscopic minimally invasive surgery and internal fixation with rib fracture preservation between January 2019 and December 2022, including 54 males and 46 females, aged from 20 to 65 years old, with an average age of (38.0±18.0)years old. The duration of the disease ranged from 8 to 21 days. According to the different surgical methods, the patients were divided into control group and study group, with 50 patients in each group. The control group consisted of 23 males and 27 females, with an average age of (38.35±18.05) years old, who underwent rib preservation periosteal internal fixation. In the study group, there were 31 males and 19 females, with an average age of (38.15±17.99) years old, treated with thoracoscopic nickel-titanium shape memory alloy circumferential bone plate. The pulmonary function indices, electrocardiographic monitoring indices, pain severity, levels of inflammatory factors, complications, rehabilitation indices, and therapeutic efficacy were compared between the two groups before and after treatment. RESULTS: All patients were followed up for 6 months. After 3 days of treatment, the heart rate of both groups was (102.43±13.74) beats per minute vs (86.26±8.06) beats per minute, respiratory rate (28.45±3.40) breaths per minute vs (22.05±2.85) breaths per minute, blood oxygen saturation (89.68±3.66)% vs (98.46±4.84)%, rest pain (3.5±0.5) points vs (2.6±0.6) points, movement pain (3.6±0.5) points vs (2.5±0.5) points, and these differences were statistically significant(P<0.05). The levels of Interleukin-6 (IL-6) (102.30±17.00) pg·ml^-1 vs (85.68±21.20) pg·ml^-1 and tumor necrosis factor-alpha (TNF-α)(33.44±4.85) pg·ml^-1 vs (18.14±4.28) pg·ml^-1 in both groups exhibited an increase post-treatment, while the C-reactive protein (CRP) (75.51±10.54) mg·L^-1 vs (60.75±9.84) mg·L^-1 demonstrated a decrease compared to pre-treatment levels. Furthermore, the study group displayed significantly lower levels than the control group (P<0.05). After 10 days of treatment, the peak expiratory flow rate (3.31±0.52) L·s^-1 vs (5.69±0.74) L·s^-1, forced expiratory volume (1.46±0.29) L vs (2.06±0.38) L, and forced vital capacity (2.68±0.95) L vs (4.26±1.05) L of both groups exhibited significant improvements compared to pre-treatment levels. Moreover, the study group demonstrated significantly higher values than the control group (P<0.05). The incidence of postoperative complications in the study group was significantly lower compared to the control group (6 cases vs 14 cases, P<0.05). Additionally, the duration of bone callus formation(9.50±1.40) days and fracture healing (72.20±8.32) days in the study group was significantly shorter compared to the control group(11.35±2.15) days, (93.70±9.90) days (P<0.001). CONCLUSION Compared with traditional rib-preserving internal fixation, patients with MRF and flail chest treated with minimally invasive internal fixation with thoracoscopic nickel-titanium shape memory alloy surround bone plate have better therapeutic effect, because of less surgical trauma, less pain and inflammatory reaction, fewer postoperative pulmonary complications, faster and better recovery of lung function, and thus promote the recovery of patients.
Humans ; Male ; Female ; Middle Aged ; Adult ; Retrospective Studies ; Rib Fractures/surgery* ; Aged ; Minimally Invasive Surgical Procedures/methods* ; Flail Chest/surgery* ; Thoracoscopy/methods* ; Fracture Fixation, Internal/methods*

The patient was a boy aged 1 year and 9 months who presented with 46,XY disorder of sex development (DSD), with severe undermasculinization of the external genitalia. Laboratory tests and ultrasound examinations showed normal functions of Leydig cells and Sertoli cells in the testes. Genetic testing revealed a novel pathogenic heterozygous variant, c.1186dupA (p.T396Nfs*17), in the PPP1R12A gene. Thirteen cases of PPP1R12A gene variants have been reported previously. These variants may cause isolated involvement of the genitourinary or neurological systems, or affect other systems/organs including the digestive tract, eyes, heart, etc. Patients with DSD typically present with a 46,XY karyotype and variable degrees of undermasculinization involving the external genitalia, gonads, and reproductive tract. This article reports a child with 46,XY DSD accompanied by growth retardation caused by a heterozygous variant in the PPP1R12A gene, which expands the clinical disease spectrum associated with PPP1R12A gene variants.
Humans ; Male ; Infant ; Disorder of Sex Development, 46,XY/etiology* ; Protein Phosphatase 1/genetics*

BACKGROUND: Early control of low-density lipoprotein cholesterol (LDL-C) is crucial for reducing the progress of cardiovascular disease. However, its additional role to the risk of primary osteoporosis in men with coronary heart disease was inconclusive. Our study aims to determine the association of LDL-C and its trajectories for osteoporosis risk in the middle-aged and aged men of China. METHODS: The retrospective cohort study of 1546 men aged 69.74 ± 11.30 years conducted in Beijing, China from 2015 to 2022. And the incidence of primary osteoporosis was annually recorded. LDL-C trajectories were further identified by latent class growth model using repeated measurements of LDL-C. The association of baseline LDL-C for osteoporosis was estimated using hazard ratio (HR) with 95% CI in Cox proportional hazard model, while mean level and trajectories of LDL-C for osteoporosis were evaluated using odds ratio (OR) with 95% CI in logistic regression model. RESULTS: During the median 6.2-year follow-up period, 70 men developed primary osteoporosis. The higher level of baseline LDL-C (HR = 1.539, 95% CI: 1.012-2.342) and mean LDL-C (OR = 2.190, 95% CI: 1.443-3.324) were associated with higher risk of osteoporosis in men with coronary heart disease after adjusted for covariates. Compared with those in the LDL-C trajectory of low-stable decrease, participants with medium-fluctuant trajectory, whose longitudinal LDL-C started with a medium LDL-C level and appeared an increase and then decrease, were negatively associated with osteoporosis risk (OR = 2.451, 95% CI: 1.152-5.216). And participants with initially high LDL-C level and then a rapid decrease demonstrated a tendency towards reduced risk (OR = 0.718, 95% CI: 0.212-2.437). CONCLUSIONS Elevated LDL-C level and its long-term fluctuation may increase the risk of primary osteoporosis in men. Early controlling a stable level of LDL-C is also essential for bone health.

The ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson's disease (PD). Notably, the VA receives direct innervation from the hypothalamic histaminergic system. However, its role in PD remains unknown. Here, we assessed the contribution of histamine to VA neuronal activity and PD motor deficits. Functional magnetic resonance imaging showed reduced VA activity in PD patients. Optogenetic activation of VA neurons or histaminergic afferents significantly alleviated motor deficits in 6-OHDA-induced PD rats. Furthermore, histamine excited VA neurons via H1 and H2 receptors and their coupled hyperpolarization-activated cyclic nucleotide-gated channels, inward-rectifier K⁺ channels, or Ca²⁺-activated K⁺ channels. These results demonstrate that histaminergic afferents actively compensate for Parkinsonian motor deficits by biasing VA activity. These findings suggest that targeting VA histamine receptors and downstream ion channels may be a potential therapeutic strategy for PD motor dysfunction.
Animals ; Histamine/metabolism* ; Male ; Oxidopamine/toxicity* ; Rats ; Ventral Thalamic Nuclei/physiopathology* ; Rats, Sprague-Dawley ; Disease Models, Animal ; Parkinson Disease/metabolism* ; Neurons/physiology* ; Humans ; Optogenetics

Attention is the cornerstone of effective functioning in a complex and information-rich world. While the neural activity of attention has been extensively studied in the cortex, the brain-wide neural activity patterns are largely unknown. In this study, we conducted a comprehensive analysis of neural activity across the mouse brain during attentional processing using EEG and c-Fos staining, utilizing hierarchical clustering and c-Fos-based functional network analysis to evaluate the c-Fos activation patterns. Our findings reveal that a wide range of brain regions are activated, notably in the high-order cortex, thalamus, and brain stem regions involved in advanced cognition and arousal regulation, with the central lateral nucleus of the thalamus as a strong hub, suggesting the crucial role of the thalamus in attention control. These results provide valuable insights into the neural network mechanisms underlying attention, offering a foundation for formulating functional hypotheses and conducting circuit-level testing.
Animals ; Attention/physiology* ; Mice ; Brain/physiology* ; Male ; Electroencephalography ; Reaction Time/physiology* ; Brain Mapping ; Mice, Inbred C57BL ; Choice Behavior/physiology* ; Proto-Oncogene Proteins c-fos/metabolism*