The concept of syndrome differentiation and treatment is often misunderstood as "arbitrary empiricism" or dismissed as unjustifiable when judged by a single external indicator. To address it， this paper draws on hermeneutics， especially the idea that "tradition， understanding， and practice" are mutually generative， to elucidate the object levels， inferential pathways， and efficacy-based validation and correction mechanisms underlying this approach in the clinical process. It is argued that "syndrome" is not a substitute for a disease label or an isolated indicator， but rather a structured configuration of manifestations and an evolving trajectory of illness situated in a specific clinical context. The correlation of all four examinations and physician-patient dialogue form a reasoned chain for the selection of diagnoses， through which discrete signs and symptoms are organized into a syndrome judgment that can be articulated and debated. Therapeutic principles and prescriptions externalize clinical understanding and， through feedback from therapeutic effects， reflexively prompt re-differentiation， thereby forming a cyclical， self-corrective dynamic loop of "syndrome， treatment and effect". Accordingly， syndrome differentiation and treatment should not be regarded as a contingent accumulation of experience， but as a form of clinical rationality under multiple constraints， including classical methods， communal training， and clinical verification.

Background Per- and poly-fluoroalkyl substances (PFAS) can influence gestational diabetes mellitus (GDM); however, current studies on their association are limited and have yielded inconsistent findings. Objective To investigate the association between maternal exposure to PFAS, as measured by urinary concentrations in early pregnancy, and the risk of developing GDM. Methods Based on the Wuhu Birth Cohort in Anhui Province conducted between 2020 and 2023, this study included 1910 pregnant women. Urine samples were collected during the first trimester, and a 75 g oral glucose tolerance test (OGTT) was completed at 24–28 gestational weeks. The concentrations of six PFAS in urine were measured using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Participants were categorized into low, medium, and high exposure groups according to tertiles of individual PFAS concentrations. Logistic regression analysis was employed to assess the potential impact of early-pregnancy PFAS exposure levels on the risk of GDM, with stratified analyses by maternal age and fetal sex. A generalized weighted quantile sum regression (gWQS) model was applied to evaluate the relative weight distribution of the six PFAS in their mixture effect. Results The logistic regression results revealed that both medium exposure to perfluorohexane sulfonate (PFHxS) (OR=1.475, 95%CI: 1.040, 2.093) and high exposure to perfluorononanoic acid (PFNA) (OR=1.430, 95%CI: 1.013, 2.018) were positively associated with diagnosed GDM. This association was more pronounced among women older than 28 years. Among pregnant women carrying male fetuses, high-level exposures to per fluorohexanoic acid (PFHxA) (OR=1.708, 95%CI: 1.006, 2.899) and PFHxS (OR=2.116, 95%CI: 1.247, 3.584) showed positive associations with diagnosed GDM. In contrast, among those carrying female fetuses, moderate perfluorooctanesulfonic acid (PFOS) exposure was associated with a lower risk of GDM (OR=0.542, 95%CI: 0.311, 0.946). The gWQS results demonstrated that PFOS (0.48) and perfluorobutane sulfonate (PFBS) (0.34) contributed the most to the mixture effect. Conclusion Early-pregnancy exposure to PFAS (particularly PFHxS and PFNA) may be an etiological factor for GDM, with maternal age and fetal sex potentially acting as effect modifiers in this association.

OBJECTIVE To evaluate the cost-effectiveness of culmerciclib combined with fulvestrant as second-line treatment for patients with hormone receptor-positive（HR+）/human epidermal growth factor receptor 2-negative （HER2–） locally advanced or metastatic breast cancer， within the context of the Chinese healthcare system. METHODS A partitioned survival model was established based on the CULMATE-1 study， with a simulation time horizon set at 15 years and a cycle length of 28 days. The incremental cost-effectiveness ratio （ICER） of culmerciclib combined with fulvestrant versus fulvestrant monotherapy as second-line treatment for HR+/HER2– breast cancer was calculated. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess the robustness of the model. Meanwhile， scenario analysis of culmerciclib price reduction was conducted； the required price reduction and price to reach the willingness-to-pay （WTP） threshold in this study were calculated. RESULTS The results of the base-case analysis indicated that， compared with the fulvestrant monotherapy regimen， culmerciclib combined with fulvestrant yielded an additional 0.823 quality-adjusted life year （QALY）， with a corresponding ICER of 371 696.26 yuan/QALY， which exceeded the WTP threshold （199 330 yuan/QALY）. The results of the univariate sensitivity analysis indicated that the cost of culmerciclib， the discount rate， the utility values for progression disease and progression free survival status were significant factors influencing the ICER； both the univariate sensitivity analysis and the probabilistic sensitivity analysis validated the robustness of the model results. Scenario analysis indicated that when the price of culmerciclib was reduced by 30%， 55% and 85% respectively， the corresponding ICER values fell below 3， 2， and 1 times China’s per capita GDP in 2025， with the probability of cost-effectiveness being 3.00%， 94.90%， 100%. When the cost of culmerciclib （60 mg） was reduced by 52.6% to 50.96 yuan， the ICER value met the WTP threshold established in this study. CONCLUSIONS When the WTP threshold is set at twice China’s per capita GDP in 2025， second-line treatment with culmerciclib combined with fulvestrant for HR+/HER2– locally advanced or metastatic breast cancer does not exhibit cost-effectiveness advantage over fulvestrant monotherapy. Therefore， a reasonable price reduction is required to alleviate the financial burden on patients.

Magnetic resonance elastography （MRE） has become an important tool for the diagnosis and staging of fibrosis in metabolic dysfunction-associated fatty liver disease （MAFLD）， and its high diagnostic accuracy can help to effectively evaluate the dynamic changes and long-term prognosis of fibrosis in patients with MAFLD. In addition， MRE also shows wide potential in patient screening and outcome assessment in new drug development for metabolic-associated steatohepatitis. This article comprehensively analyzes the potential value of MRE in evaluating liver fibrosis in MAFLD patients， as well as its advantages in clinical practice and future development directions.

ObjectiveThis paper aims to investigate the differential mechanisms underlying the staged therapeutic effects of Qijia Rougan formula on liver fibrosis using proteomic technology. MethodsThe staged rat model of liver fibrosis was established by subcutaneous injection of carbon tetrachloride （CCl₄） and olive oil. One hundred and four SD rats were randomized into thirteen groups：a normal group，a two-week model group，a four-week model group，a six-week model group，an eight-week model group，a two-week Qijia Rougan formula group，a four-week Qijia Rougan formula group，a six-week Qijia Rougan formula group，an eight-week Qijia Rougan formula group，a two-week compound Biejia Ruangan tablet group，a four-week Compound Biejia Ruangan Tablet group，a six-week Compound Biejia Ruangan Tablet group，and an eight-week compound Biejia Ruangan tablet group. After two weeks of drug intervention，liver tissue and abdominal aortic blood samples were collected from the rats for testing. Hematoxylin-eosin （HE） staining，Masson staining，and Picro Sirius red staining were used to observe pathological damage and collagen fiber deposition in liver tissues. Immunohistochemistry （IHC） was employed to detect the contents of fibrosis markers in liver tissues. The contents of liver function indicators in the serum were measured using a fully automated biochemical analyzer，and the levels of liver fibrosis indicators in the serum were assessed by enzyme-linked immunosorbent assay （ELISA）. Liver tissues from the normal group，each model group，and each Qijia Rougan formula group were subjected to label-free quantitative proteomic analysis to identify differential proteins among the groups，with key proteins validated by Western blot. Finally，bioinformatics analysis was performed on the differential proteins. Results（1） The staged rat model of liver fibrosis constructed with CCl₄ and olive oil showed pathological results at the 2^nd，4^th，6^th，and 8^th weeks of modeling that were consistent with the Metavir standards for the F1，F2，F3，and F4 stages. Compared with those in the normal control group，the protein expressions of α-smooth muscle actin （α-SMA） and Collagen Ⅰ were significantly increased in each stage （P<0.05）. The levels of liver function indicators in the serum，including alanine aminotransferase （ALT），aspartate aminotransferase （AST），alkaline phosphatase （ALP），direct bilirubin （DBIL），and total bilirubin （TBil） in each model group，were significantly elevated in each stage （P<0.01）. The levels of liver fibrosis indicators in the serum，including procollagen Ⅲ peptide （PⅢP），type Ⅳ collagen（Ⅳ-C），hyaluronic acid （HA），and laminin （LN） in each model group，were significantly increased in each stage （P<0.05，P<0.01）. This study successfully established a staged rat model of liver fibrosis. （2） Compared with the model groups at each stage，the administration groups showed a reduction in hepatocyte ballooning degeneration，a more orderly arrangement of hepatocytes，and a decrease of inflammatory cell infiltration. The blue-stained collagen fibers became significantly thinner and finer，with reduced and narrowed fibrous septa. The areas of collagen fibers and Picro Sirius red staining were reduced （P<0.05）. The positive areas of α-SMA and Collagen Ⅰ expression were significantly decreased （P<0.05）. The levels of ALT，AST，ALP，DBIL，and TBil in the rats of the model groups at each stage were significantly reduced （P<0.05，P<0.01）. The levels of PⅢP，Ⅳ-C，HA，and LN in the rats of the model groups at each stage were significantly decreased （P<0.05）. Among these，the improvements in all indicators were most significant in the F3 stage （P<0.01）.（3） The proteomic results show that a total of 165 differential proteins exhibit a callback trend when comparing the model groups at four stages with the normal group，and when comparing the Qijia Rougan formula group with the model group. Western blot analysis reveals that the levels of NAD（P）H：quinone oxidoreductase 1 （NQO1），mitogen-activated protein kinase 1 （MAPK1），arginase 1 （Arg1），and glutathione S-transferase α1 （GSTA1） were consistent with the proteomic results. Bioinformatics results reveal that 165 differentially expressed proteins are enriched in multiple signaling pathways. Notably，signaling pathways such as drug metabolism-cytochrome P450，arginine biosynthesis，and the peroxisome proliferator-activated receptor （PPAR） signaling pathway were found to be closely associated with liver fibrosis，suggesting that the Qijia Rougan formula may exert its staged regulatory effects on liver fibrosis by regulating these pathways. ConclusionThe Qijia Rougan formula may achieve staged regulation of liver fibrosis by regulating drug metabolism-cytochrome P450，arginine biosynthesis，and the PPAR signaling pathway.

Objective: To address the lack of fine-grained clinical recognition for specific Yang deficiency syndrome subtypes and the limitations of conventional object detection models in extracting irregular, low-contrast tongue phenotypes. This study aims to develop an objective subtype recognition framework based on an improved You Only Look Once nano (YOLO11n) architecture, using a standardized visual phenotype matrix to translate macroscopic traditional Chinese medicine (TCM) descriptions into quantifiable clinical targets. Methods: This cross-sectional diagnostic study consecutively enrolled adult inpatients admitted to the Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Wannan Medical University (Yijishan Hospital), between September 1, 2024 and June 1, 2025, who were suspected of having Yang deficiency constitution based on initial TCM consultation. Clinical tongue image data were collected for analysis. Based on an Expert Visual Phenotype Annotation Matrix, a five-category recognition system was established, including the following TCM syndrome subtypes: spleen-dampness exuberance syndrome, mild kidney Yang deficiency syndrome, upper heat and lower cold syndrome, simultaneous Yin-Yang deficiency syndrome, and Yin deficiency and fluid depletion syndrome (negative control). The proposed Yang deficiency YOLO (YD-YOLO) model, built upon the YOLO11n baseline, integrates the Cross Stage Partial with kernel size 2 (C3k2)-GhostBottleneck-Dynamic Convolution (GBDC) module into the backbone to adaptively extract low-contrast features, and embeds the multipath aggregation coordinate attention (MACA) mechanism into the neck to suppress background interference through multi-scale spatial coordination. Gradient-weighted class activation mapping (Grad-CAM) was used to visualize feature attribution and evaluate the biological plausibility of the model’s focus. Model performance was evaluated through ablation and comparative experiments using mean average precision (mAP), precision, recall, F1 score, inference speed (frames per second, FPS), overall accuracy, Cohen’s kappa, and the area under the receiver operating characteristic (ROC) curve (AUC). Results: Based on the final inclusion of 1 186 clinical cases, the YD-YOLO model had an overall accuracy of 91.5%, a Cohen’s kappa of 0.912, and an mAP@50 of 0.731 [higher than the YOLO11n baseline (0.681)], with AUC ranging from 0.91 to 0.97 across all TCM syndrome subtypes. Among the TCM syndrome subtypes, the mild kidney Yang deficiency syndrome had the highest mAP@50 (0.900), and the inference speed reached 89.00 FPS. Grad-CAM analysis showed that the model localized activation to key TCM pathological features, such as marginal tooth marks and focal root coatings, while suppressing non-diagnostic oral background noise. Conclusion The YD-YOLO model demonstrates the feasibility of deep learning for the fine-grained classification of TCM Yang deficiency subtypes. By integrating visual phenotype quantification with model interpretability, the proposed framework provides an objective basis for syndrome differentiation, supporting the development of standardized digital diagnostic systems and the provision of clinical decision support in TCM practice.

Objective:To analyze the clinical features of patients with traumatic optic neuropathy (TON) and to explore its clinical patterns and treatment outcomes.Methods:A retrospective analysis was conducted on data from 323 patients (334 eyes) with TON, who were treated in the Department of Otorhinolaryngology Head and Neck Surgery, the Affiliated Hospital of Qingdao University from April 1999 to October 2024. Among these patients, 288 were male and 35 were female, with ages ranging from 4 to 70 years. All patients were followed up for a period of 6 to 24 months, with the final follow-up visual acuity recorded as the ultimate visual outcome. The visual acuity evaluation criteria were classified into five levels: no light perception, light perception, hand movement in front of the eye, counting fingers at 1 meter, and "chart-visible acuity". A treatment outcome was deemed effective if the post-treatment visual acuity improved by one level or more compared to pre-treatment, or if the chart-visible acuity improved by two lines or more on the logMAR chart. The clinical characteristics of patients, causes of injury, complications, treatment methods, and changes in visual acuity before and after treatment were summarized. Logistic regression analyses were performed to identify the influencing factors affecting treatment efficacy.Results:TON occurred mostly in young (215/323, 66.56%) males (288/323, 89.16%), the majority of patients came from villages and towns (236/323, 73.07%). Traffic accidents (232/323, 71.83%) remained the main etiology. Most patients had craniofacial injuries and other bodily injuries. The effective rate of vision improvement was 50.30% (168/334). Multiple logistic regression analyses identified that residual vision (light perception or better) at presentation ( OR=3.26, P<0.001) and receiving treatment within 7 days after injury ( OR=2.04, P=0.008) were protective factors on visual acuity recovery, while the presence of orbital wall fracture was a risk factor for visual acuity recovery ( OR=0.26, P<0.001). Additionally, undergoing surgical treatment was a protective factor for visual improvement in patients with no light perception ( OR=2.94, P=0.007). For patients with residual vision at presentation, orbital wall fracture was a significant risk factor ( OR=0.28, P=0.009). Conclusions:TON is more prevalent in young males and is primarily caused by traffic accidents, leading to a poor prognosis. Timely medical intervention following injury significantly influences prognostic outcomes. Early surgical intervention (within 7 days) is recommended, particularly for patients with no light perception at presentation.

The legal and regulatory system for the import of blood products in China has undergone a three-stage evolution of"safety first,demand-driven and standard upgrading",ultimately forming a dual control framework that centers on infectious disease prevention and control as well as quality approval.While the current policy effectively ensures biosafety,it also faces several deep-seated contradictions.These include the worsening imbalance between supply and demand,limited access to clinically needed blood products,and insufficient alignment with international standards.Moreover,strict regulation has also constrained technological innovation and market diversification.To address these challenges,it is suggested to establish a synergy mechanism that integrates a"clinical urgent need list,"hierarchical supervision,and mutual recognition of Good Manufacturing Practice(GMP).By implementing dynamic access,risk classification management,and international certification mutual recognition,it is possible to achieve compatible development between the safety baseline and medical accessibility.

Objective:To observe the effects of acupuncture on the motor function of Parkinson disease(PD)model mice and to investigate the neuroprotective effects of acupuncture on PD from the perspective of cellular senescence.Methods:C57BL/6J mice were randomly divided into a normal control(NC)group,a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)group,an acupuncture(ACU)group,and a rasagiline(RAS)group,with 6 mice in each group.Except for the mice in the NC group,all mice were injected intraperitoneally with MPTP[30 mg/(kg·bw)]to establish a PD mouse model.After the models were successfully established,mice in the ACU group received acupuncture at Baihui(GV20)and bilateral Yanglingquan(GB34)for 15 min,once a day for 14 consecutive days.Mice in the RAS group were treated with gavage of rasagiline mesylate[0.5 mg/(kg·bw)],once daily for 14 d.Mouse balance and motor functions were detected using the mouse fatigue rotating rod apparatus.Immunohistochemistry staining was used to detect the number of tyrosine hydroxylase(TH)-positive neurons and the protein expression levels of special AT-rich sequence-binding protein 1(SATB1),p21,and p53 in the substantia nigra(SN)region of the mouse brain in each group.The glutathione peroxidase(GSH-Px)activity of mouse brain SN tissue was detected by enzyme-linked immunosorbent assay.The protein expression levels of interleukin(IL)-6 and senescence-associated β-galactosidase(SA-β-gal)in the SN tissue of mice in each group were detected by Western blotting.The relative expression of SATB1,p21,and p53 mRNA in the SN of each group was detected by real-time quantitative polymerase chain reaction.Results:Compared to the NC group,the overall rod performance(ORP)score,the number of TH-positive neurons,and GSH-Px activity in the SN region were significantly lower in the mice in the MPTP group(P<0.01);compared to the MPTP group,the ORP score,the number of TH-positive neurons,and GSH-Px activity were significantly increased in the ACU group and the RAS group(P<0.01 or P<0.05).Compared to the NC group,the protein levels of IL-6 and SA-β-gal in the SN tissue,the protein and mRNA expression levels of p21 and p53 were significantly increased(P<0.01);compared to the MPTP group,the protein levels of IL-6 and SA-β-gal in the SN tissue,the protein and mRNA expression levels of p21 and p53 were significantly decreased in the ACU group and the RAS group(P<0.01 or P<0.05).Compared to the NC group,the relative expression of SATB1 protein and mRNA in the SN of mice in the MPTP group was significantly decreased(P<0.01);compared to mice in the MPTP group,mice in the ACU group and the RAS group showed significant increases in the relative expression of SATB1 protein and mRNA(P<0.01 or P<0.05).Conclusion:Acupuncture can improve motor function and increase the number of TH-positive neurons in the SN of PD model mice.Its neuroprotective effect may relate to the regulation of the SATB1/p21 signaling pathway and the inhibition of cellular senescence-related biomarker expression in the SN.

Objective:To quantitatively assess the participation of social medical insurance in palliative care medical insurance payment policies in different regions of China,explore the characteristics,find the weak points,and provide a basis for subsequent policy formulation.Methods:Based on text mining and literature review,it established a Policy Modeling Consistency(PMC)index model with 9 primary indicators and 38 secondary indicators,and quantitatively evaluated the palliative care insurance payment policies from 2017 to 2024.Results:A total of 24 policies were included,and the overall PMC index was 5.65,which was an acceptable grade,including 10 good grade policies,13 acceptable grade policies,and 1 poor grade policy.Conclusion:Overall,palliative care medical insurance payment policies are good,with relatively complete provisions in terms of coverage,medical insurance payment mechanism,supervision and management.However,there are still shortcomings in terms of financing channels,policy recipients,and incentive constraints.The follow-up should focus on broadening the financing channels,expanding the scope of recipients,and improving the incentive and constraint mechanism,so as to promote the optimization and improvement of the palliative care insurance payment system.