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.

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.

Traditional Chinese medicine （TCM） cultural tourism integration is an important form of TCM culture dissemination and health service expansion. To address conceptual generalization， insufficient theoretical interpretation， short-term experiential activities， and traffic-oriented evaluation in current research and practice of TCM cultural tourism， this paper analyzes the conversion process of "knowledge-practice-value" in TCM cultural tourism from the perspective of cultural translation. It is argued that cultural translation should be based on the academic ontology of TCM， utilizing knowledge， practice， and value translation to transform professional TCM discourse into cultural expressions that the public can understand， participate in， and identify with. Cultural explanation， spatial embedding， and narrative construction are treated as the main implementation paths， while "cognition-experience-identification" is introduced as the basic analytical framework to evaluate the effectiveness of cultural translation. Accordingly， this paper examines the deficiencies of cultural translation in TCM cultural tourism integration regarding ontological integrity， daily life integration， fashionability， and internationalization. Furthermore， it proposes optimization paths such as improving academic interpretation， expanding daily practice scenarios， updating media expressions， and strengthening cross-cultural interpretation， thereby promoting the shift of TCM cultural tourism from static knowledge display to living practice， and from short-term experience to stable identification.

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.

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.

Objective:To establish a method for the rapid detection of varicella-zoster virus (VZV) by recombinase-aid amplification (RAA) combined with Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a system.Methods:Clinical samples of suspected herpes zoster in Shandong province and Shanghai from 2023 to 2024 were collected, nucleic acids of positive samples were extracted, RAA-specific primers and crRNA (CRISPR RNA, crRNA) were designed for the conserved region of VZV, and the fluorescence intensity generated by Cas12a non-specific cleavage of single-stranded fluorescent probes was used to screen highly sensitive crRNAs and optimize the concentrations of crRNA, Cas12a and ssDNA probes. The sensitivity and reproducibility of the RAA-CRISPR/Cas12a detection method were evaluated by using synthesized plasmids and clinical samples, and the specificity of the method was evaluated by using other viral nucleic acids. The method was used to detect clinical samples by using the method and quantitative real-time PCR (qPCR) method, and the detection rate and consistency of the two method were compared.Results:The highly sensitive crRNA-4 was screened from the four crRNAs designed, and a VZV detection method for RAA-CRISPR/CAS12a based on fluorescence intensity measurement was established, which could be detected at 37℃ in 45 min, and the sensitivity of the detection could reach 10 copies/μL, a minimum clinical sample with a Ct value of 38.980 can be detected. It has high specificity and no cross-reactivity with Adenovirus 7, Herpes simplex virus type I, Herpes simplex virus type II, Coxsackieviruses A16, Cytomegalovirus, Epstein-Barr virus, Measles virus, Mumps virus, Enterovirus 71, Japanese encephalitis virus genotype 5. It has good stability, and can be successfully detected in low, medium and high concentrations of viral positive plasmids with good consistency. The detection rate of the clinically positive samples was 100%, which was completely consistent with the qPCR test result.Conclusions:RAA isothermal amplification technology combined with CRISPR-CAS12a technology was used to establish an accurate method for the detection of VZV virus, which was highly sensitive, specific, and had low requirements for experimental conditions, and could be completed within 45 min, which could provide strong technical support for the early detection of VZV.

Objective:To evaluate the efficacy and safety of treatments in phase Ⅰ oncology clinical trials in patients with advanced non-small-cell lung cancer(NSCLC).Methods:We retrospectively analyzed the clinical data of 65 patients with advanced NSCLC who received phase Ⅰ antitumor trial drugs at the Clinical Trial Research Center of The First Affiliated Hospital of Bengbu Medical University from January 2020 to December 2023.The efficacy and occurrence of serious adverse events(SAEs)were analyzed.Results:The objective response rate(ORR)and disease control rate(DCR)were 9.2%and 61.4%,respectively,whereas the median progression-free survival(PFS)and overall survival(OS)were 2.9 and 15.1 months,respectively.Previously receiving second-line or more lines of treatment and SAE occurrence were independent risk factors for a shorter PFS(P<0.05).A history of smoking and previous second-line or more lines of treatment were inde-pendent risk factors for a shorter OS(P<0.05).The SAE incidence was 15.4%,and no treatment-related deaths occurred.Conclusions:Treat-ments in phase Ⅰ oncology clinical trials are beneficial for patients with advanced NSCLC.Patients with a higher number of previous treat-ment lines and those who experienced SAEs during the trial had a shorter PFS,whereas patients with no smoking history and fewer previous treatment lines had a longer overall survival.The overall safety of the treatments was acceptable.

Objective:To evaluate the association between heatwaves and fall-related mortality.Methods:A total of 61 421 fall-related mortality from 2013 to 2022 in 7 provinces of China were included in a time-stratified case-crossover design, with daily meteorological data derived from the fifth generation European Reanalysis dataset produced by the European Centre for Medium-Range Weather Forecasts. Conditional logistic regression chimeric distributed lag nonlinear model was used to analyze the association between heatwaves and fall-related mortality and stratified analysis was conducted according to gender and age.Results:Heatwaves were associated with an increased risk of fall-related morality. The risk of fall-related mortality during heatwaves was higher than during non-heatwave periods ( OR=1.11, 95% CI: 1.05-1.18). The attributable fraction of fall-related motality due to heatwaves was 10.25% (95% CI: 4.49%-15.36%). For each 1 ℃ increase above the heatwave threshold, the risk of fall-related mortality increased by 34% ( OR=1.34, 95% CI: 1.02-1.76). The effect of heatwave duration on fall-related mortality was not statistically significant. Stratified analyses indicated that women experienced a higher risk of fall-related mortality during heatwaves ( OR=1.13, 95% CI: 1.04-1.22) compared to man ( OR=1.10, 95% CI: 1.04-1.17). Conclusions:Heatwave increases the risk of fall-related mortality, and the intensity of heatwaves modify this risk. Women are vulnerable populations.