ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally， the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome， such as oral ulcers， sore throat， and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation， oxidative stress， and energy metabolism in the early phase， Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting （XGBoost） algorithm was used to develop a prediction model for main symptom classification， with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers， sore throat， and overall symptoms， with significant effects observed especially in sore throat and overall symptom analyses （P<0.01）. Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement， were also called "heat-related biomarkers"， including succinic acid， α-ketoglutaric acid， glycine， lactic acid， adenosine monophosphate （AMP）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-10 （IL-10）， and so on. Conversely， clinical biomarkers negatively correlated with symptom severity， were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan， including malic acid， fumaric acid， cis-aconitic acid， adrenocorticotropic hormone （ACTH）， IL-1β， IL-4， IL-8， succinic acid， and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables， with importance scores of 0.081 and 0.080， respectively. After screening out 14 key variables and optimizing the parameters， model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables， confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established， achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.

ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally， the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome， such as oral ulcers， sore throat， and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation， oxidative stress， and energy metabolism in the early phase， Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting （XGBoost） algorithm was used to develop a prediction model for main symptom classification， with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers， sore throat， and overall symptoms， with significant effects observed especially in sore throat and overall symptom analyses （P<0.01）. Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement， were also called "heat-related biomarkers"， including succinic acid， α-ketoglutaric acid， glycine， lactic acid， adenosine monophosphate （AMP）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-10 （IL-10）， and so on. Conversely， clinical biomarkers negatively correlated with symptom severity， were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan， including malic acid， fumaric acid， cis-aconitic acid， adrenocorticotropic hormone （ACTH）， IL-1β， IL-4， IL-8， succinic acid， and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables， with importance scores of 0.081 and 0.080， respectively. After screening out 14 key variables and optimizing the parameters， model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables， confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established， achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.

Mucosae are the primary sites of causing infectious diseases in human beings. The high transmissibility and mortality rates of infectious diseases pose a serious threat to human health. Mucosal vaccines, which induce both mucosal and systemic immune responses, have emerged as an effective method for preventing or treating infectious diseases. This paper provides an overview of the structure and response characteristics of the mucosal immune system, as well as adjuvants and delivery vectors in vaccine design. It focuses on the multi-dimensional evaluation system of immunoprotective efficacy,covering key indicators such as antibody response, neutralization ability, antibody affinity and tissue-resident memory cells,providing reference for the future development of more effective mucosal vaccines.

Objective To investigate the post-discharge exercise behavior and factors influencing moderate to vigorous intensity physical activity (MVPA) in patients undergoing lung surgery. Methods A total of 2874 patients from the large prospective, observational perioperative lung symptom study cohort (CN-PRO-Lung 3) in the Department of Thoracic Surgery at Sichuan Cancer Hospital between April 7, 2021, and January 31, 2024, were selected as the survey subjects. A survey was conducted using the Investigation of Exercise Behavior after Lung Surgery questionnaire and the International Physical Activity Questionnaire-Short Form (IPAQ-SF) among patients who underwent lung surgery. Binary logistic regression was used to analyze the factors influencing patients’ engagement in MVPA. Results A total of 702 patients were surveyed, including 252 males and 450 females, with an average age of (52.4±10.2) years. Patients with lung cancer accounted for 85.9%. Only 36.0% of the patients had regular exercise habits, while 42.3% did not engage in any physical activity. The three main barriers for postoperative exercise were physical discomfort (pain, coughing, shortness of breath, etc, 54.7%), lack of professional guidance (41.7%), and concerns about the surgical wound (28.9%). The proportions of patients engaging in vigorous, moderate, and low-intensity physical activity were 5.7%, 28.2%, and 66.1%, respectively. Multivariate analysis showed that patients with a personal annual income ≥50000 yuan (OR=1.52, 95%CI 1.01-2.29, P=0.044), high school education or above (OR=1.92, 95%CI 1.33-2.76, P<0.001), and lobectomy (OR=1.44, 95%CI 1.02-2.03, P=0.037) engaged in more MVPA. Conclusion Patients undergoing lung surgery have inadequate physical activity after discharge, particularly lacking in MVPA. Patients with higher income, higher educational levels, and lobectomy are more frequently engaged in MVPA. Measures such as symptom control, providing exercise guidance, and enhancing education on wound care may potentially improve the inadequate physical activity in lung surgery patients after discharge.

Health economics evidence plays an important role in linking clinical value evidence with health resource allocation decisions in the development of clinical practice guidelines. It can not only effectively balance clinical effectiveness and economic feasibility but also avoid forming "idealized" recommendations that are detached from the affordability of the healthcare system or the burden-bearing capacity of patients. To promote guideline developers to use health economics evidence more standardizedly and fully, this paper conducts an in-depth analysis of the current application status, existing challenges, access channels, and application processes of health economics evidence in current guidelines, and on this basis, puts forward considerations and suggestions for strengthening and standardizing the application of health economics evidence in China's clinical practice guidelines.

ObjectiveTo systematically summarize the relevant pathophysiology underlying muscle fatigue in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). MethodsDatabases including PubMed, Web of Science Core Collection, Embase, Cochrane Library, EBSCO (CINAHL), CNKI, Wanfang Data and VIP Database were searched from their inception to July, 2025 for basic and clinical studies related to ME/CFS. Multidimensional evidence involving mitochondrial, neuromuscular junction dysfunction, autonomic dysregulation and immune-inflammatory responses was integrated. The role of muscles in the central-immune-metabolic-neural regulatory network and its association with clinical phenotypes were evaluated. ResultsPatients with ME/CFS commonly presented with impaired mitochondrial energy supply, oxidative stress, ion homeostasis disorders, reduced stability of neuromuscular junction transmission, insufficient central drive and postural intolerance. These abnormalities resulted in a predisposition to cross the anaerobic threshold and trigger post-exertional malaise. ConclusionMuscle pathophysiology plays a critical role in the pathogenesis and symptom persistence of ME/CFS. Rehabilitation practice should prioritize safety boundaries to avoid post-exertional malaise.

ObjectiveTo explore the mechanisms of Salviae Miltiorrhizae Radix et Rhizoma in treating metabolic hypertension induced by a high-sugar and high-fat diet in rats based on network pharmacology， proteomics， and animal experiments. MethodsThirty male SD rats were randomized into the control， model， positive drug （tetrandrine， Tet， 50 mg·kg^-1·d^-1）， low-dose Salviae Miltiorrhizae Radix et Rhizoma （DS-L， 45×10⁴ mg·kg^-1·d^-1）， and high-dose Salviae Miltiorrhizae Radix et Rhizoma （DS-H， 90×10⁴ mg·kg^-1·d^-1） groups. Except for the control group， each group was fed a high-fat and high-sugar diet for 8 weeks for the modeling of metabolic hypertension. Following successful modeling， drug interventions were conducted through gavage for 4 weeks. Blood pressure and lipid indicators were monitored， and cardiac function was assessed via echocardiography. Samples from the thoracic aorta and cardiac tissue were collected for histopathological examination. Network pharmacology analysis identified key active components， potential targets， and mechanisms of Salviae Miltiorrhizae Radix et Rhizoma in treating hypertension. Proteomics technology was employed to analyze the differential proteins and major pathway targets to synergistically elucidate the antihypertensive mechanism of Salviae Miltiorrhizae Radix et Rhizoma. Ca²⁺ concentrations in the thoracic aorta and cardiac tissue were measured. The protein levels of transient receptor potential cation channel （TRPC）3， TRPC6， NADPH oxidase （NOX）2， and NOX4 were quantified via Western blotting. The levels of oxidative stress markers and inflammatory factors， including superoxide dismutase （SOD）， malondialdehyde （MDA）， tumor necrosis factor-α （TNF-α）， and interleukin-1β （IL-1β）， were determined by enzyme-linked immunosorbent assay （ELISA）. Molecular docking analysis was performed for the main components of Salviae Miltiorrhizae Radix et Rhizoma with TRPC3， TRPC6， NOX2， and NOX4. ResultsThe experimental results indicated that compared with the control group， the model group exhibited abnormally elevated blood pressure and increased lipid levels （P<0.01）. Compared with the model group， the DS-L group exhibited reduced systolic blood pressure （SBP）， diastolic blood pressure （DBP）， and mean arterial pressure （MAP） （P<0.05）， decreased serum levels of triglycerides （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） （P<0.05）， and increased level of high-density lipoprotein cholesterol （HDL-C） （P<0.01）. The DS-H and Tet groups showed more significant effects （P<0.01）. Moreover， the interventions attenuated vascular wall thickening， myocardial cell injury， and collagen and lipid deposition. Network pharmacology and proteomics prediction results indicated that the core targets of Salviae Miltiorrhizae Radix et Rhizoma in treating hypertension were TRPC3， TRPC6， NOX2， and NOX4， and the core pathways included calcium signaling， cyclic guanosine monophosphate （cGMP）/cGMP-dependent protein kinase （PKG） signaling， and atherosclerosis-related pathways. The molecular mechanism experiment results indicated that compared with the control group， the model group exhibited significantly elevated tissue Ca²⁺ concentrations， exacerbated oxidative stress and inflammatory responses， and upregulated protein levels of TRPC3， TRPC6， NOX2， and NOX4 in the thoracic aorta and myocardial tissue （P<0.01）. Compared with the model group， DS-L reduced the free Ca²⁺ concentration， lowered the levels of IL-1β， TNF-α， SOD， and MDA （P<0.05）， and downregulated the protein levels of TRPC3， TRPC6， NOX2， and NOX4 in the thoracic aorta and myocardial tissue （P<0.05）. DS-H and Tet exhibited more significant effects （P<0.01）. Meanwhile， the main components of Salviae Miltiorrhizae Radix et Rhizoma had strong binding affinity with the core targets of hypertension. ConclusionSalviae Miltiorrhizae Radix et Rhizoma may ameliorate oxidative stress and mitigate inflammatory responses by regulating the TRPC3/6/NOX2/4 signaling pathway， thereby alleviating abnormal blood pressure abnormality and myocardial injury in hypertensive rats.

As people’s attention to health continues to increase, the market demand for traditional Chinese medicine (TCM) is growing steadily. The quality and safety of Chinese medicinal materials have attracted unprecedented social attention. In particular, the issue of exogenous harmful residue pollution in TCM has become a hot topic of concern for both regulatory authorities and society. The Chinese Pharmacopoeia 2025 Edition further refines the detection methods and limit standards for exogenous harmful residues in TCM. This not only reflects China’s high-level emphasis on the quality and safety of TCM but also demonstrates the continuous progress made by China in the field of TCM safety supervision. Basis on this study, by systematically reviewing the development history of the detection standards for exogenous harmful residues in TCM and analyzing the revisions and updates of these detection standards in the Chinese Pharmacopoeia 2025 Edition, deeply explores the key points of the changes in the monitoring standards for exogenous harmful residues in TCM in the Chinese Pharmacopoeia 2025 Edition. Moreover, it interprets the future development directions of the detection of exogenous residues in TCM, aiming to provide a reference for the formulation of TCM safety supervision policies.

Dental implant surgery,an established practice,has been widely used in patients with dentition defect.Dental implanta-tion-induced osteomyelitis of the jaw is a rare complication.Osteomyelitis of the jaw is an inflammatory change of the jaw caused by bac-terial infection or other physical and chemical factors involving the whole bone tissue,such as periosteum,blood vessels and nerves in the medullary cavity,etc.Due to protracted course and complicated treatment of the disease,the consequences will be serious if not swiftly managed.Here,an unusual case of severe mandibular osteomyelitis following mandibular implant surgery is reported.Also,re-lated literature is reviewed to elucidate the clinical characteristics and management as to highlight the understanding of this complication and provide reference for clinical prevention,diagnosis and treatment.

Objective:To evaluate the short-and medium-term therapeutic efficacy of shockwave balloon therapy for TASCⅡ C/D femoropopliteal artery atherosclerosis obliteration.Methods:This retrospective cohort study included 25 patients who received shockwave balloon therapy in five vascular centers from August 2022 to June 2023. All patients were diagnosed with TASC Ⅱ C/D femoropopliteal arteriosclerosis obliterans (13 cases of type C and 12 cases of type D), and underwent intravascular shock wave lithotripsy (IVL) to treat calcified lesions. The immediate effectiveness (residual stenosis<30% and no flow-limiting dissection), safety (whether there were adverse vascular events during the operation) and the rate of salvage stent implantation were recorded. The observation indexes of patients before operation, early postoperative period (immediately after operation or before discharge) and postoperative follow-up period (3, 6, 12 months after operation) were collected. The observation indexes included ankle-brachial index (ABI), Rutherford classification, and minimum lumen diameter (MLD). Repeated measures ANOVA was used to evaluate the changes of observation indexes in the early postoperative and follow-up stages compared with those before operation; Kaplan-Meier survival analysis was used to evaluate the one-stage patency rate at follow-up and the target lesion revascularization rate free from clinical drive.Results:The immediate effectiveness of surgery was 100% in all patients, with no vascular related adverse events occurred, and no remedial stent implantation was performed. The ABI, Rutherford grade and MLD of the patients in the early postoperative period and each follow-up stage were improved compared with those before operation, with statistically significant differences ( P<0.05). Kaplan-Meier survival analysis showed that the primary patency rate at 12 months after surgery was 0.78 (95% CI 0.64-0.84), and the revascularization rate of target lesions free from clinical drive was 0.87 (95% CI 0.85-0.95). Conclusion:Shockwave balloon therapy for complex calcified femoropopliteal artery lesions is safe and reliable, with satisfactory short-and medium-term efficacy.