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.

Lung cancer is a leading cause of cancer-related morbidity and mortality worldwide. Coupled with the substantial workload, the clinical management of lung cancer is challenged by the critical need to efficiently and accurately process increasingly complex medical information. In recent years, large language models (LLMs) technology has undergone explosive development, demonstrating unique advantages in handling complex medical data by leveraging its powerful natural language processing capabilities, and its application value in the field of lung cancer diagnosis and treatment is continuously increasing. The paper systematically analyzes that the exceptional potential of LLMs in lung cancer auxiliary diagnosis, tumor feature extraction, automatic staging, progression/outcome analysis, treatment recommendations, medical documentation generation, and patient education. However, they face critical technical and ethical challenges including inconsistent performance in complex integrated decision-making (e.g., TNM staging, personalized treatment suggestions) and "black box" opacity issues, along with dilemmas such as training data biases, model hallucinations, data privacy concerns, and cross-lingual adaptation challenges ("data colonization"). Future directions should prioritize constructing high-quality multimodal corpora specific to lung cancer, developing interpretable and compliant specialized models, and achieving seamless integration with existing clinical workflows. Through dual drivers of technological innovation and ethical standardization, LLMs should be prudently advanced for holistic lung cancer management processes, ultimately promoting efficient, standardized, and personalized diagnosis and treatment practices.

BACKGROUND:The formation of postoperative abdominal adhesions is a complicated process,and the prevention of postoperative adhesions is an urgent problem in clinic. OBJECTIVE:To analyze the mechanism of adhesion at cellular and molecular levels,and to provide theoretical basis for the prevention and treatment of adhesion by mesenchymal stem cell exosomes. METHODS:"Abdominal adhesion,pelvic adhesion,postoperative adhesion,epithelial mesenchymal transformation,mesenchymal stem cells,stem cell exosomes,mesenchymal stem cell exosomes"were selected as Chinese and English search terms.We searched PubMed,CNKI,and Chinese biomedical literature and screened relevant articles on postoperative abdominal adhesion and mesenchymal stem cell exosomal intervention published from inception to August 2023.After systematic analysis,54 articles were finally included for the review. RESULTS AND CONCLUSION:(1)Any pathological factors such as peritoneal inflammation,mechanical injury,tissue ischemia,and foreign body implantation cause peritoneal surface injury,resulting in postoperative abdominal adhesion.The formation process of adhesion includes the interaction of peritoneal mesothelial cell repair,inflammatory response,fibrinolytic system,coagulation pathway and other processes,involving a variety of cytokines and signaling pathways.Wnt/β-catenin pathway can induce fibrosis and angiogenesis,and cooperate with transforming growth factor-β/Smads signaling pathway to stimulate fibroblast proliferation and cause peritoneal fibrosis.Meanwhile,nuclear factor-κB signaling pathway up-regulates the expression of cellular inflammatory factors,promotes fibroblast proliferation,and plays a key role in the process of tissue fibrosis.(2)The paracrine function of stem cells is an important direction of molecular intervention in abdominal adhesions based on regenerative medicine.It can participate in a variety of complex cytokines and signaling pathways involved in abdominal adhesions.(3)Compared with traditional methods for treating abdominal adhesions,mesenchymal stem cell exosome has biological activity and is safe to use.Mesenchymal stem cell exosomes without special culture and expansion have lower immunogenicity,longer stability and other advantages,can guide a normal repair and healing through a variety of ways.(4)Mesenchymal stem cell exosome has been proven to be involved in regulating the above processes of adhesion formation in previous studies,showing potential application prospects in clinical studies.However,further clinical studies are needed to explore appropriate treatment options for mesenchymal stem cell exosomes to address the problem of clinical translation.

INTRODUCTION: Comparison of patient health-related quality of life (HRQOL) scores to a reference group is needed to quantify the HRQOL impact of disease or treatment. This study aimed to establish population norms for 2 HRQOL questionnaires-EuroQol 5-dimension 5-level questionnaire (EQ-5D-5L) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Question-naire 30 (EORTC QLQ-C30) according to age, sex and ethnicity-and to explore relationships between the EQ-5D-5L, EORTC QLQ-C30 and sociodemographic characteristics. We used a representative sample of adult Singapore residents aged 21 years and above. METHOD: This study used data collected from a cross-sectional household survey in which 600 adult Singaporeans completed questions on sociodemo-graphic characteristics-the EQ-5D-5L and the EORTC QLQ-C30. Multiple linear regression analyses were conducted to explore associations between sociodemographic characteristics, the EQ-5D-5L scores and the EORTC QLQ-C30 scores. Regression-based population norms were computed for each subgroup using a post-stratification method. RESULTS: In multiple linear regression analysis, age was significantly associated with EQ-5D-5L index and visual analogue scale (VAS) scores, while no sociodemographic characteristics were significantly associated with EORTC QLQ-C30 summary scores. The normative EQ-5D-5L index and VAS scores decreased in adults aged 65 years and above, and EQ-5D-5L index scores were slightly lower in females than males and in non-Chinese than Chinese. The normative EORTC QLQ-C30 summary scores were slightly higher in Chinese than in the non-Chinese group and in the 45-64 age group than other age groups. CONCLUSION This study provides population norms for the EQ-5D-5L and EORTC QLQ-C30 for the general adult population in Singapore. Future studies of patient populations in Singapore using EQ-5D-5L or QLQ-C30 can use these normative data to interpret the HRQOL data collected.
Humans ; Quality of Life ; Singapore ; Male ; Female ; Middle Aged ; Adult ; Cross-Sectional Studies ; Aged ; Surveys and Questionnaires ; Young Adult ; Health Status ; Age Factors ; Linear Models ; Aged, 80 and over

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

General anesthesia is widely used in clinical practice,whereas the exact mechanism behind the general anesthetic-induced reversible loss of consciousness remains unclear.Recent studies have revealed a close relationship between the dopaminergic system and general anesthetic-induced loss of consciousness.This system,encompassing dopamine neurons,dopamine receptors,and related neural pathways,regulates functions such as movement,memory,arousal,and cognition.The dopaminergic neurons in the ventral periaqueductal gray and ventral tegmental area,along with D1 receptors,have been shown to facilitate emergence from anesthesia.However,the role of D2 receptors remains controversial.This review summarizes recent advancements in the role of the dopaminergic system in general anesthesia and the underlying mechanism,with the aim of clarifying the mechanism of general anesthesia and providing a theoretical basis for preventing delayed emergence from anesthesia.
Humans ; Anesthesia, General ; Brain/metabolism* ; Dopaminergic Neurons/physiology* ; Dopamine/physiology* ; Animals

OBJECTIVE To analyze the correlation between styloid process related parameters and symptoms in patients with styloid process syndrome.METHODS A retrospective study was conducted on the 3D reconstruction CT results of the styloid process in 68 patients diagnosed with styloid process syndrome who visited the Department of Otolaryngology Head and Neck Surgery,the Second Affiliated Hospital of Xi'an Jiaotong University from January 2010 to December 2024.The relationship between parameters such as styloid process length,angle,distance from styloid process tip to pharynx,and specific symptoms in patients with styloid process syndrome was analyzed.RESULTS Among 68 patients with styloid process syndrome,44 had unilateral symptoms and 24 had bilateral symptoms.The length of the styloid process on the symptomatic side of patients with unilateral symptoms(3.86±0.16)cm was significantly longer than that on the asymptomatic side(2.98±0.17)cm(Z=-2.191,P=0.028);The length of the styloid process on the side with severe symptoms in patients with bilateral symptoms(3.98±0.37)cm was also significantly longer than that in patients with mild symptoms(3.37±0.15)cm(t=2.448,P=0.024).Patients with styloid process syndrome mainly present with pharyngalgia(64.71%,44/68).There were no significant differences in the length,inclination angle,anteversion angle,and distance between the styloid process tip and the pharynx among those with unilateral pharyngalgia(n=29),bilateral pharyngalgia(n=15),and non pharyngalgia(n=24)(P>0.05).However,among the 68 patients with styloid syndrome,12 had calcification of the styloid hyoid ligament,while 56 did not.The incidence of unilateral pharyngalgia was significantly higher in patients with calcification of the styloid hyoid ligament than in patients without calcification(66.7%vs.35.7%,χ2=3.909,P=0.048).CONCLUSION The severity of symptoms in patients with styloid process syndrome is related to the length of the styloid process,and those with calcification of the styloid hyoid ligament are more likely to experience pharyngalgia.

Objective To investigate the relationship between the five-circuit and six-qi characteristics of birth dates and the prevalence of endometriosis(EMs).Methods Clinical data from 333 EMs patients treated at the Department of Reproductive Medicine,The First Affiliated Hospital of Henan University of Chinese Medicine between March 2022 and March 2025 were collected.Statistical analysis was performed on parameters of the five circuits and six qi of patients' birth dates.Results No statistically significant differences were found in the distribution of heavenly stems,dominant circuits,guest circuits,dominant qi,guest qi,joining of guest qi with dominant qi,or Sitian-Zaiquan among the 333 EMs patients(all P＞0.05).However,significant differences were observed in the distribution of earthly branches,yearly circuits,and circuit-qi combinations(P＜0.05 or P＜0.01).Specifically:(1)The most frequent earthly branch was the"Wei"year(12.3％,41/333);(2)The most common annual circuit was"deficient water circuit"(14.7％,49/333);(3)The predominant circuit-qi combination was"Tong Sui Hui"(23.1％,77/333).Conclusion The development of EMs is associated with specific five circuits and six qi characteristics at birth:(1)Earthly branch of"Wei"year;(2)Annual circuit of"deficient water circuit";(3)Circuit-qi combination of"Tong Sui Hui".These patterns suggest that congenital endowmentl deficiencies in the spleen and kidney systems may predispose individuals to EMs.

Objective To construct fluorescent molecular probes targeting at tumor heat shock protein 90(Hsp90)in order to enhance tumor-specific recognition.Methods The human pancreatic adenocarcinoma cell line PANC-1 and the human small cell lung cancer cell line NCI-H446 were used as the research targets to study the uptake and clearance of Cy5-P7 by tumor cells with flow cytometry as well as immune-fluorescence technology;The mechanism to mediate entrance of Cy5-P7 into the cells by Hsp90 was investigated by blocking of the PANC-1 cell surface pro-teins with monoclonal antibody to Hsp90;Human pancreatic cancer cell line PANC-1 was subcutaneously injected into posterior dorsum of BALB/c nude mice to construct a xenogeneic subcutaneous tumor model to validate the in vivo tumor recognition ability by Cy7-P7 as well as its in vivo distribution in mice.Results The uptake of Cy5-P7 by cells was significantly reduced in low temperature(P<0.05);An average fluorescence intensity in Cy5-P7-trea-ted cells was significantly reduced after blocking with a monoclonal antibody to Hsp90(P<0.05);The fluorescence intensity at the tumor site of Cy7-P7 group was higher than that of control group(P<0.05),and there was a significant presence of Cy7-P7 in the kidney and tumor fluorescence.Conclusions Cy5-P7 can effectively target at Hsp90,and its specific binding significantly enhanced the cellular uptake of Cy5-P7 fluorescent probe,which im-proved the sensitivity and accuracy of fluorescence imaging.Cy7-P7 showed good tumor active recognition in vivo,and was able to be enriched at the tumor site and metabolized out of the body in 48 h,which may effectively sup-port accurate tumor recognition.