ObjectiveTo observe the clinical effectiveness and safety of Qingfei Shenshi Decoction （清肺渗湿汤） combined with western medicine for patients with bronchial asthma of heat wheezing syndrome， and to explore its potential mechanism of action. MethodsEighty-six participants with bronchial asthma of heat wheezing syndrome were randomly divided into treatment group and control group， each group with 43 participants. The control group received conventional western medicine， and the treatment group was additionally administered Qingfei Shenshi Decoction orally on the basis of the control group， 1 dose per day. Both groups were treated for 14 days. The primary outcome measure was clinical effectiveness； secondary outcome measures included traditional Chinese medicine （TCM） syndrome score， asthma control test （ACT） score， pulmonary function indices such as forced expiratory volume in 1 second （FEV₁）， forced vital capacity （FVC）， peak expiratory flow （PEF）， serum inflammatory factor levels including interleukin-4 （IL-4）， tumour necrosis factor-α （TNF-α）， and high-sensitivity C-reactive protein （hs-CRP）， and immune function indices including CD3⁺， CD4⁺， CD8⁺， CD4⁺/CD8⁺. All outcome measures were evaluated before and after treatment. Vital signs were monitored， and electrocardiography， blood routine， urine routine， liver function， and renal function tests were performed before and after treatment. Adverse events and reactions during the study were recorded. ResultsA total of 80 patients completed the trial with 40 in each group. The total clinical effective rate of the treatment group was 97.5% （39/40）， which was significantly higher than that of the control group （85.0%， 34/40， P＜0.05）. After treatment， both groups showed decreased TCM syndrome scores， IL-4， TNF-α， hs-CRP， and CD8⁺ levels， as well as increased ACT scores， CD3⁺， CD4⁺， CD4⁺/CD8⁺， FEV₁， FVC， and PEF levels （P＜0.05 or P＜0.01）. Moreover， the improvements in these indices were more significant in the treatment group than in the control group （P＜0.05 or P＜0.01）. No significant abnormalities in safety indicators were observed in either group， and no adverse events or reactions occurred. ConclusionQingfei Shenshi Decoction combined with conventional western medicine for patients with bronchial asthma of heat wheezing syndrome can effectively improve the clinical symptoms， pulmonary function， and clinical effectiveness， with good safety. Its mechanism may be related to reducing inflammatory factor levels and regulating T lymphocyte subsets to improve immune function.

Objective: To develop a clinical decision and prescription generation system (CDPGS) specifically for diarrhea in traditional Chinese medicine (TCM), utilizing a specialized large language model (LLM), Qwen-TCM-Dia, to standardize diagnostic processes and prescription generation. Methods: Two primary datasets were constructed: an evaluation benchmark and a fine-tuning dataset consisting of fundamental diarrhea knowledge, medical records, and chain-of-thought (CoT) reasoning datasets. After an initial evaluation of 16 open-source LLMs across inference time, accuracy, and output quality, Qwen2.5 was selected as the base model due to its superior overall performance. We then employed a two-stage low-rank adaptation (LoRA) fine-tuning strategy, integrating continued pre-training on domain-specific knowledge with instruction fine-tuning using CoT-enriched medical records. This approach was designed to embed the clinical logic (symptoms → pathogenesis → therapeutic principles → prescriptions) into the model’s reasoning capabilities. The resulting fine-tuned model, specialized for TCM diarrhea, was designated as Qwen-TCM-Dia. Model performance was evaluated for disease diagnosis and syndrome type differentiation using accuracy, precision, recall, and F1-score. Furthermore, the quality of the generated prescriptions was compared with that of established open-source TCM LLMs. Results: Qwen-TCM-Dia achieved peak performance compared to both the base Qwen2.5 model and five other open-source TCM LLMs. It achieved 97.05% accuracy and 91.48% F1-score in disease diagnosis, and 74.54% accuracy and 74.21% F1-score in syndrome type differentiation. Compared with existing open-source TCM LLMs (BianCang, HuangDi, LingDan, TCMLLM-PR, and ZhongJing), Qwen-TCM-Dia exhibited higher fidelity in reconstructing the “symptoms → pathogenesis → therapeutic principles → prescriptions” logic chain. It provided complete prescriptions, whereas other models often omitted dosages or generated mismatched prescriptions. Conclusion By integrating continued pre-training, CoT reasoning, and a two-stage fine-tuning strategy, this study establishes a CDPGS for diarrhea in TCM. The results demonstrate the synergistic effect of strengthening domain representation through pre-training and activating logical reasoning via CoT. This research not only provides critical technical support for the standardized diagnosis and treatment of diarrhea but also offers a scalable paradigm for the digital inheritance of expert TCM experience and the intelligent transformation of TCM.

OBJECTIVE To establish a method for simultaneous determination of plasma concentration of lamotrigine（LTG）， levetiracetam（LEV） and perampanel（PER） in children with epilepsy and apply this method in clinical practice. METHODS Plasma proteins were precipitated with acetonitrile. Using PER-D 5 as internal standard， ultra-high performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） method was adopted. The determination was performed on ACQUITY UPLC HSS T3 C 18 column with mobile phase consisted of 0.1% formic acid with 5 mmol/L ammonium acetate-acetonitrile （gradient elution） at the flow rate of 0.3 mL/min. The column temperature was 40 ℃， and sample size was 5 μL. The analysis time was 5 min. The electrospray ionization source and multiple reaction monitoring mode were used for positive ion scanning. The ion pairs used for quantitative analysis of LTG， LEV， PER and internal standard were m / z 255.9→144.9， m / z 171.1→126.1， m / z 350.1→219.0 and m / z 354.9→220.2， respectively. The steady-state trough concentrations of the aforementioned drugs in the plasma of 14 pediatric epilepsy patients receiving combination therapy were determined using the same UPLC-MS/MS method as above. RESULTS The linear ranges of LTG， LEV and PER were 0.15-24 μg/mL （ R 2 ＞0.993）， 0.312 5-50 μg/mL （ R 2 ＞0.997） and 6.25-1 000 ng/mL （ R 2 ＞0.997）， respectively. The lower limits of quantification were 0.15 μg/mL， 0.312 5 μg/mL and 6.25 ng/mL， respectively. RSDs of intraday and interday precision tests of the three drugs were no more than 9.83%， and the accuracies （relative errors） were between －9.33% and 13.72%（ n ＝6 or n ＝18）； the average extraction recovery rates were 86.4%-97.9%， and the average matrix effects were 86.9%-110.0% （ n ＝6）. The absolute values of the relative errors in the stability tests were all below 15%. The steady-state trough concentrations of LTG， LEV and PER were （5.64±4.03）μg/mL， （10.67±8.78）μg/mL and（450.20±251.27）ng/mL， respectively； the rates of achieving target trough concentrations were 71.4%， 37.5% and 84.6%， respectively. CONCLUSIONS The established UPLC-MS/MS method is specific， rapid and suitable for the plasma concentration monitoring in epileptic children receiving combination therapy.

Natural products (NPs) have long held a significant position in various fields such as medicine, food, agriculture, and materials. The chemical space covered by NPs is extensive but often underexplored. Therefore, high-throughput and efficient methodologies for the annotation and discovery of NPs are desired to address the complexity and diversity of NP-based systems. Mass spectrometry (MS) has emerged as a powerful platform for the annotation and discovery of NPs. MS databases provide vital support for the structural characterization of NPs by integrating extensive mass spectral data and sample information. Additionally, the released annotation methodologies, based on a variety of informatics tools, continuously improve the ability to annotate the structure and properties of compounds. This review examines the current mainstream databases and annotation methodologies, focusing on their advantages and limitations. Prospects for future technological advancements are then discussed in terms of novel applications and research objectives. Through a systematic overview, this review aims to provide valuable insights and a reference for MS-based NPs annotation, thereby promoting the discovery of novel natural entities.
Biological Products/chemistry* ; Mass Spectrometry/methods* ; Databases, Factual ; Drug Discovery/methods* ; Humans

This paper summarized Professor ZHOU Zhaoshan's clinical experience in treating bronchial asthma （abbreviated as asthma） by stages with dampness-draining method. It is believed that pathogenic dampness is the key pathological factor in the onset of asthma. Dampness accumulates into water， which gathers into rheum； the condensed rheum forms phlegm， which lingers in the lungs. When external pathogens trigger the latent phlegm， phlegm and qi become mutually obstructed， leading to airway obstruction， disrupted qi movement， and upward reversal of lung qi， thereby resulting in asthma attacks. The treatment emphasizes a stage-based approach. During acute attacks， the main syndromes include cold-damp obstructing the lungs， damp-heat accumulating in the lungs， and shaoyang （少阳） constraint with heat. For the syndrome of cold-damp obstructing the lungs， a self-formulated Wenfei Shenshi Decoction （温肺渗湿汤） is used to warm the lungs and disperse cold， drain dampness and relieve panting； for the syndrome of damp-heat accumulating in the lungs， a self-formulated Qingfei Shenshi Decoction （清肺渗湿汤） is employed to clear the lungs and expel heat， drain dampness and relieve asthma； and for the syndrome of shaoyang constraint with heat， a self-formulated Chaihu Shenshi Decoction （柴胡渗湿汤） is administered to harmonize the shaoyang， clear heat and drain dampness. During the remission stage， treatment is based on the underlying kidney-deficiency constitution， and a self-formulated Bushen Shenshi Decoction （补肾渗湿汤） is formulated to tonify the kidneys and drain dampness， improve qi reception and relieve panting.

Objective:To investigate the interventional effect of Rhizoma Corydalis on mice with ulcerative colitis(UC)induced by dextran sulfate sodium(DSS),as well as the potential mechanism of Rhizoma Corydalis in the treatment of UC based on metabolomics and inflammation biomarkers.Methods:A mouse model of UC was established,and then the mice were divided into model group,high-dose group(1.517 g/kg crude drug),middle-dose group(0.986 g/kg crude drug),low-dose group(0.455 g/kg crude drug),and positive drug group(5-aminosalicylic acid at a dose of 718.8 mg/kg),while the mice without modeling were selected as normal group(0.9%NaCl by gavage).The mice in each group were administered for 7 consecutive days,and phenotypic parameters were dynamically moni-tored,such as body weight change,disease activity index(DAI),mean daily food intake,and daily water intake.The mice were sacri-ficed after 7 days to collect serum and colon tissue samples;ELISA was used to measure the serum levels of the proinflammatory fac-tors interleukin-6(IL-6),interleukin-17A(IL-17A),C-reactive protein(CRP),and tumor necrosis factor-α(TNF-α),and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)was used to perform the non-targeted metabolomics analysis and compare the differences in se-rum metabolite profiles between groups.The mice were selected for modeling and validation with the same method,and glutathione(GSH)was selected as the positive drug.Colon length and mucosal damage were assessed,and quantitative real-time PCR was used to measure the relative mRNA expression levels of the key genes in the glutathione synthesis pathway(γ-glutamylcysteine synthetase[γ-GCS]and oxidative stress regulators yap1p and skn7)and mito-chondrial GSH transporter protein(Slc25a39)in colonic tissue.Results:Rhizoma Corydalis significantly improved weight loss,DAI,and colon length in a dose-dependent manner in the model animals,and there were reductions in the serum levels of IL-6,CRP,and TNF-α,while it had no significant effect on IL-17A.The metabolomics analysis revealed 21 potential biomarkers associated with amino acid and lipid metabolism,which were significantly regulated by Rhizoma Corydalis.In the verification experiment,both Rhi-zoma Corydalis and GSH exerted a significant protective effect against colonic mucosal damage without affecting colon length.Rhizoma Corydalis upregulated the expression of genes associated with glutathione synthesis,especially γ-GCS,suggesting that Rhizoma Co-rydalis could enhance intestinal antioxidant defenses.Conclusion:Rhizoma Corydalis has a therapeutic potential in a mouse model of DSS-induced UC and can alleviate symptoms,reduce the serum levels of inflammatory markers,and regulate metabolic pathways,and upregulation of the genes associated with glutathione synthesis suggests that the drug can enhance intestinal antioxidant defenses.

Objective:To explore the effects of childhood trauma on resting blood pressure, heart rate, and heart rate variability in patients with depression.Methods:A cross-sectional study was designed to prospectively collect clinical data on a total of 163 patients with depression, including 47 males and 116 females, aged 18-50 years,with mean[ M( Q1, Q3)] [29.0, (21.0, 37.0)]years, who were either the outpatients or the inpatients in the Mental Health Center of the First Hospital of Hebei Medical University from September 2022 to June 2024. The Childhood Trauma Questionnaire-Short form (CTQ-SF) was used to assess the experience of abuse and neglect during childhood. According to the CTQ-SF score, the subjects were divided into a trauma group ( n=80) and a non-trauma group ( n=83). The 17-item Hamilton Depression Scale (HAMD 17) and Hamilton Anxiety Scale (HAMA) were used to assess depressive and anxiety symptoms in the participants, respectively. A digital blood pressure monitor and an autonomic nervous system response detector were employed to measure resting blood pressure, heart rate, and heart rate variability (HRV). Spearman correlation analysis was used to examine the relationships between childhood trauma and resting blood pressure, heart rate, and HRV. Multiple linear regression analysis was performed to analyze factors influencing these parameters. The Bootstrap method was employed to test the potential mediating role of parasympathetic nervous system activity in the relationships between childhood trauma and resting blood pressure, and heart rate. Results:No significant difference was observed in resting heart rate between the trauma and non-trauma groups ( P>0.05). However, the trauma group exhibited higher resting systolic and diastolic blood pressure [(123.3±9.1) mmHg (1 mmHg=0.133 kPa) vs(116.9±10.8) mmHg, (80.0±8.6) mmHg vs (77.0±8.0) mmHg; Z=4.08, 2.24, all P<0.05]. HRV indices, including the standard deviation of normal to normal interval (SDNN), root mean square of successive differences (RMSSD), total power (TP), low frequency (LF), and high frequency (HF), were significantly lower in the trauma group [25.3 (19.4, 30.4) me vs 36.3 (27.4, 49.0) ms, 18.3 (12.9, 27.2) me vs 26.2 (19.0, 38.5) ms, 6.0(5.4, 6.5)ms 2vs 7.0(6.3, 7.4)ms 2,4.4(3.7,5.3)ms 2vs 5.8(4.9,6.3)ms 2, 4.2(3.4, 5.2)ms 2vs 5.2(4.6, 6.1)ms 2, respectively; all P<0.001]. Spearman correlation analysis showed that childhood trauma experiences in patients with depression were positively correlated with resting systolic blood pressure and diastolic blood pressure ( r=0.309, 0.236; P<0.01), childhood trauma was negatively correlated with HRV (SDNN, RMSSD, TP, LF, HF) ( r=-0.264, -0.274, -0.271, -0.235, -0.279; all P<0.01). Multiple linear regression analysis showed that childhood trauma was positively correlated with resting-state systolic blood pressure and resting-state diastolic blood pressure ( β=0.305, 0.291; all P<0.001). Childhood trauma was negatively correlated with RMSSD, TP, LF, and HF( β=-0.244, -0.249, -0.233, -0.263; all P<0.01). Mediation effect analysis showed that parasympathetic activity partially mediated the relationship between childhood trauma and resting systolic blood pressure (effect size 0.04, standard error 0.02, 95% CI=0.01-0.09), accounting for 14.29% (0.04/0.28) of the total effect. Conclusion:Childhood trauma experiences are associated with elevated resting blood pressure and reduced HRV in patients with depression. Decreased parasympathetic activity partially mediates the relationship between childhood trauma and elevated resting systolic blood pressure in these patients.

Objective:To investigate the radiation field distribution characteristics in a 9 MeV electron FLASH (e-FLASH) linear accelerator treatment room.Methods:The Geant4 Monte Carlo program was employed for physical simulating of the radiation field distribution inside and outside the treatment room under a single-beam delivery condition with a total dose of 50 Gy at the reference point and a dose rate of 250 Gy/s. High-sensitivity radiation detectors (AT1123) were used to validate the measurements at key points.Results:The dose rate at the reference point was approximately 9×10 11 μSv/h. Due to the scattering and shielding effects, the deviation of the attenuation rate from the inverse-square law was observed and the isodose lines exhibited spatial drift. Measured dose rates at key points showed good agreement with the simulation result, with a maximum deviation within 30%. Conclusions:The complex radiation field distribution can be effectively simulated using Geant4 in an e-FLASH treatment room. This indicated the Geant4 is not only applicable for the shielding calculations in e-FLASH radiotherapy facilities, but also for the design optimization through, reduction of trial-and-error iterations and engineering costs.

Objective:To explore the clinical efficacy of suture-bridge techniques assisted by our self-designed novel auxiliary sleeve in arthroscopic repair of large rotator cuff tear.Methods:A retrospective analysis was conducted of the clinical data of 35 patients with large rotator cuff tear who had been treated by the arthroscopic suture-bridge technique assisted by our novel auxiliary sleeve at Department of Orthopaedics, The People’s Hospital of Shanxi Province from July 2022 to January 2024. The 35 patients were set as an observation group [14 males and 21 females with an age of (58.3±10.3) years]. According to a 1:1 ratio, another 35 patients with large rotator cuff tear who had been treated by simple arthroscopic suture-bridge technique from January 2021 to June 2022 were selected as a control group [15 males and 20 females with an age of (55.3±10.5) years]. The perioperative efficacy between the 2 groups was evaluated by comparing operation time, total length of incision, and disparity in hemoglobin level between preoperation and postoperative day 1. The American Shoulder and Elbow Surgeons (ASES) score, University of California, Los Angeles (UCLA) score, and visual analogue scale (VAS) pain score at 3 months after operation were compared between the 2 groups to evaluate the functional recovery and shoulder pain relief, and comparisons of the 3 scores were also made between preoperation and 3 months after operation in each group.Results:There were no statistically significant differences in the general preoperative data between the 2 groups, indicating comparability ( P > 0.05). The 70 patients were followed up for 5.7 (5.0, 7.0) months after operation. No such complications as recurrent rotator cuff tear, poor wound healing, infection, or anchor withdrawal occurred in either group after operation. The operation time in the observation group was 133.3 (120.0, 140.0) min, significantly shorter than 171.7 (140.0, 200.0) min in the control group ( P < 0.05). In the control group, the ASES and UCLA scores increased significantly from 29.1 (27.5, 31.4) points and 11.8 (10.0, 13.0) points before operation to 56.0 (51.9, 59.5) points and 24.6 (22.0, 27.0) points at 3-month follow-up, respectively, and the VAS pain score decreased significantly from preoperative 8.1 (7.0, 10.0) points to 2.0 (2.0, 2.0) points at 3-month follow-up ( P < 0.05). In the observation group, the ASES and UCLA scores increased significantly from 29.9 (29.1, 31.2) points and 12.6 (11.0, 14.0) points before operation to 58.8 (53.1, 62.2) points and 26.7 (25.0, 29.0) points at 3-month follow-up, respectively, and the VAS pain score decreased significantly from preoperative 8.0 (7.0, 9.0) points to 1.9 (2.0, 2.0) points at 3-month follow-up ( P < 0.05). At 3 months after operation, the UCLA score for the observation group was significantly better than that for the control group ( P < 0.05). There were no significant differences between the 2 groups in total length of incision, hemoglobin level disparity, ASES score or VAS pain score at 3 months after operation ( P > 0.05). Conclusion:In arthroscopic repair of large rotator cuff tear with suture-bridge techniques, application of our novel auxiliary sleeve can shorten operation time, simplify surgical procedures, and achieve good shoulder joint function and efficacy without increasing the length of surgical incision.

Objective:To investigate the relationship between oxidative stress-related genes and pros-tate cancer(PCa)from a multi-omics perspective using summary-data-based Mendelian randomization(SMR),colocalization analysis,and cellular experiments.Methods:Summary-level data on DNA methylation,gene expression,and circulating proteins were obtained and filtered.The PRACTICAL con-sortium was used as the discovery cohort,with the deCODE database serving as the validation cohort.SMR analysis and heterogeneity in dependent instruments(HEIDI)tests were conducted to assess the association and heterogeneity between oxidative stress-related genes and PCa.Colocalization analysis was performed to determine whether oxidative stress-related genes and PCa shared common causal variants.Final-ly,CCK-8 assays,wound healing assays,and Transwell invasion assays and Western blotting,were con-ducted to examine the effects of oxidative stress-related genes on the biological behavior of the PCa cell line C4-2.Results:Multi-omics analysis identified SCP2 as significantly associated with increased PCa risk across gene methylation,gene expression,and circulating protein levels.GSTP1 showed significant associations at the methylation and protein levels,while LPO was associated at the protein level.At the methylation level,SCP2 sites cg00581603(OR=1.11,95％CI:1.05-1.17)and cg13078931(OR=1.12,95％CI:1.05-1.18)were identified as pathogenic.Among the four methylation sites in GSTP1,only cg05244766(OR=0.89,95％CI:0.84-0.95)was considered protective.At the gene expression level,SCP2(OR=1.05,95％CI:1.02-1.07)was also found to be a pathogenic factor.At the circu-lating protein level,SCP2(OR=2.10,95％CI:1.34-3.29)showed a consistent pathogenic trend.In addition,GSTP1(OR=1.16,95％CI:1.07-1.25)and LPO(OR=1.12,95％CI:1.05-1.19)were significantly associated with increased PCa risk.Further functional assays demonstrated that knock-down of SCP2 significantly reduced the oncogenic phenotype of prostate cancer cells.Conclusion:Through integrated multi-omics analysis and experimental validation,this study confirmed a significant as-sociation between SCP2 and increased PCa risk.These findings enhance our understanding of PCa patho-genesis and provide new potential targets and therapeutic directions for PCa treatment.