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.

Vascular dementia （VaD） is a cognitive dysfunction syndrome caused by cerebrovascular disease and is the second most common type of dementia worldwide， following Alzheimer's disease. The pathological mechanisms of VaD are complex， involving multiple biological processes， including angiogenesis， neuroinflammation， apoptosis， and oxidative stress. Among these， angiogenesis is a key process in VaD pathology and is primarily regulated through the vascular endothelial growth factor （VEGF） signaling pathway. In recent years， traditional Chinese medicine （TCM） has gradually gained attention in the treatment of VaD， particularly the therapeutic approach of benefiting Qi， activating blood circulation， and resolving blood stasis， which has demonstrated unique advantages in clinical practice. This method， based on the TCM theory of Qi and blood， emphasizes improving the pathological state of ''blood stasis'' by harmonizing the circulation of Qi and blood， and its scientific basis has been increasingly elucidated by modern pharmacological studies. This article systematically integrates the TCM concept of ''removing stasis to promote regeneration'' with the modern medical mechanism of neoangiogenesis and reviews the current research on promoting neoangiogenesis through the benefiting Qi， activating blood circulation， and resolving blood stasis in VaD treatment. It covers research progress on single Chinese medicine and compound formulas that promote neoangiogenesis， reduce apoptosis， and improve cerebral hemodynamics through multi-target and multi-pathway synergistic effects. Furthermore， this article explores the therapeutic approach of combining acupuncture and moxibustion with Chinese medicine formulas， breaking through the traditional single-treatment model. The synergistic treatment of acupuncture and herbal medicine not only enhances neoangiogenesis but also improves cognitive function and quality of life in VaD patients via multiple pathways. By comparing the advantages and limitations of modern medicine and TCM in VaD treatment， this article notes that while modern medicine excels in elucidating pathological mechanisms and targeted therapies， it is limited in overall regulation and multi-target interventions. TCM， through the comprehensive effects of multiple components and targets， is better suited to address the complex pathological features of VaD. However， current research on TCM for VaD still has limitations， including incompletely clarified mechanisms and insufficient clinical studies. Therefore， future research should further integrate multidisciplinary approaches， such as modern pharmacology and molecular biology， to deeply explore TCM resources and investigate diverse interdisciplinary collaborative treatment models， providing new ideas and strategies for VaD therapy.

OBJECTIVE: To evaluate the clinical outcomes and explore the application of partial sialoadenectomy for the treatment of benign tumors in the submandibular gland (SMG). METHODS: Patients with pleomorphic adenoma of the SMG who underwent surgical treatment in the Department of Oral and Maxillofacial Surgery, Peking University Shenzhen Hospital, from October 2017 to February 2021, were enrolled and assessed in the follow-up. Fifteen patients underwent partial sialoadenectomy (PS group), and 18 patients underwent total sialoadenectomy (TS group). Postoperative salivary secretion, degree of dry mouth, appearance changes of the face and neck, nerve damage, and tumor recurrence were compared between the groups. The volume of the glands on the operated and contralateral sides of the patients in the PS group, the saliva flow rate, and their correlations, were also analyzed. RESULTS: There was no recurrence during the follow-up period. The whole saliva flow rate at rest in the PS group was higher than that in the TS group [(2.15±1.10) g/5 min vs. (1.35±0.97) g/5 min, t=2.208, P=0.035)], while the stimulated saliva flow rate was not significantly different. The objective feeling of dry mouth, evaluated by visual analogue scale (VAS) score, was more obvious in the TS group than in the PS group (Z=-2.244, P=0.025). In the PS group, the resting saliva flow rate of the SMG on the operated side was lower than that on the contralateral side of the same patient [(0.92±0.40) g/5 min vs. (1.18±0.40) g/5 min, t=-2.821, P=0.014], however, in the cases whose remaining SMG was more than 80% of the contralateral side, the saliva flow rate of both sides was not significantly different (t=-0.027, P=0.980). There was no significant difference in the saliva flow rate per unit volume of the gland on either side (t=-0.015, P=0.989), and the saliva flow rate of the operated SMG was positively correlated with the volume of the remaining gland (r=0.750, P=0.012). The VAS scores for neck deformity were not significantly different between the two groups (t=-0.997, P=0.319). No symptoms of nerve injury occurred in either group. CONCLUSION Partial sialoadenectomy in the SMG can safely remove benign tumors while preserving glandular secretory function, with fewer complications and improved quality of life.
Humans ; Submandibular Gland/pathology* ; Male ; Female ; Middle Aged ; Adenoma, Pleomorphic/surgery* ; Adult ; Treatment Outcome ; Submandibular Gland Neoplasms/surgery* ; Saliva/metabolism* ; Aged

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Objective:To investigate the effect of early high-sucrose diet (eHSD) on cognitive function and its regulatory mechanism in 3×Tg-AD mice.Methods:(1) Eighteen specific-pathogen-free (SPF)-grade 2-month-old wide-type (WT) mice were randomly divided into a WT+normal chow diet (NCD) group and a WT+eHSD group, with 9 mice in each group; and 18 SPF-grade 2-month-old 3×Tg-AD mice were randomly divided into a 3×Tg-AD+NCD group and a 3×Tg-AD+eHSD group, with 9 mice in each group. At 2-5 months old, mice in the 4 groups received standard laboratory food+purified water or 30% sucrose water, followed by standard feed for all groups. At 8 months old, cognitive function was assessed by Morris water maze test; fluorescent intensity of AT8 (phosphorylated [p]-tau) and T22 (tau oligomers) in the hippocampal tissues was detected by immunofluorescent staining; concentrations of β-amyloid protein (Aβ) 42 and Aβ 40 were detected by enzyme-linked immunosorbent assay (ELISA); protein expressions of stimulator of interferon genes (STING), TANK-binding kinase 1 (TBK1), p-TBK1, and CCAAT/enhancer-binding protein β (C/EBPβ) were detected by Western blotting; activity of C/EBPβ transcription factor was detected by activity assay; mitochondrial DNA (mtDNA) content in the cytoplasm of cell was detected by real-time quantitative PCR (qPCR). (2) Eighteen SPF-grade 2-month-old 3×Tg-AD mice were randomized into a 3×Tg-AD+eHSD+H-151 group and a 3×Tg-AD+eHSD+dimethyl sulfoxide (DMSO) group, with 9 mice in each group. Mice at 2-5 months old were given standard laboratory food+30% sucrose water; they were, respectively, injected intraperitoneally with STING pathway inhibitor H-151 or DMSO at 5 months old, and continually injected until 8 months old; and then, the behavioral testing, immunofluorescent staining, ELISA, Western blotting and C/EBPβ transcription factor activity experiments were repeated as before. (3) After crossing C/EBPβ heterozygous knockout (C/EBPβ +/-) mice with 3×Tg-AD mice, 3×Tg-AD/C/EBPβ +/- mice were obtained, and 3×Tg-AD mice were used as controls; they were named 3×Tg-AD/C/EBPβ +/-+eHSD group and 3×Tg-AD+eHSD group, with 9 mice in each group. Both groups of mice were given standard laboratory food+30% sucrose water at 2-5 months old, followed by standard feed until 8 months old; and then, the behavioral testing, immunofluorescent staining, ELISA, and Western blotting experiments were repeated as before. (4) C/EBPβ transgenic mice (C/EBPβTg) were crossed with 3×Tg-AD mice to obtain C/EBPβTg/3×Tg-AD mice, and Non-Tg/3×Tg-AD mice were used as controls; they were, respectively, named as C/EBPβTg/3×Tg-AD+eHSD+H-151 group, Non-Tg/3×Tg-AD+eHSD+H-151 group, and Non-Tg/3×Tg-AD+eHSD+DMSO group, with 9 mice in each group. All 3 groups of mice were given standard laboratory food+30% sucrose water at 2-5 months old; at 5-8 months old, mice in the C/EBPβTg/3×Tg-AD+eHSD+H-151 group and Non-Tg/3×Tg-AD+eHSD+H-151 group were intraperitoneally injected with H-151, while mice in the Non-Tg/3×Tg-AD+eHSD+DMSO group were injected with DMSO; and then, the behavioral testing, immunofluorescent staining, ELISA, and Western blotting experiments were repeated as before. Results:(1) Compared with those in the WT+NCD group and WT+eHSD group, area under the latency curve of 3×Tg-AD+eHSD mice was significantly increased, and proportion of time spending in the targeted quadrant of mice in the 3×Tg-AD+NCD group and 3×Tg-AD+eHSD group was significantly decreased ( P<0.05); compared with that in the 3×Tg-AD+NCD group, proportion of time spending in the targeted quadrant in mice of the 3×Tg-AD+eHSD group was significantly reduced ( P<0.05). Compared with the 3×Tg-AD+NCD group, the 3×Tg-AD+eHSD group had significantly increased p-tau and tau oligomers, Aβ 42 and Aβ 40 concentrations in the hippocampus (AT8 fluorescent intensity: 1.000±0.076 vs. 2.902±0.399; T22 fluorescent intensity: 1.000±0.145 vs. 2.495±0.273; Aβ 42: 1.000±0.167 vs.1.956±0.132; Aβ 40: 1.000±0.226 vs.1.900±0.116), significantly increased C/EBPβ protein expression and C/EBPβ transcription factor activity (1.000±0.164 vs. 1.804±0.112; 1.000±0.216 vs. 2.743±0.301), and statistically increased mtDNA level detected by D-loop1 and D-loop3 (1.000±0.234 vs. 2.800±0.210; 1.000±0.155 vs. 2.952±0.078; P<0.05). Compared with the 3×Tg-AD+NCD group, the 3×Tg-AD+eHSD group had significantly increased STING protein expression and p-TBK1/TBK1 ratio (STING: 1.000±0.192 vs. 2.093±0.081; p-TBK1/TBK1: 1.000±0.148 vs. 1.561±0.112, P<0.05). (2) Compared with the 3×Tg-AD+eHSD+DMSO group, the 3×Tg-AD+eHSD+H-151 group had significantly decreased area under the latency curve, significantly increased proportion of time spending in the targeted quadrant, significantly decreased p-tau and tau oligomers expressions, Aβ 42 and Aβ 40 concentrations in the hippocampus (AT8 fluorescent intensity: 1.000±0.142 vs. 0.538±0.057; T22 fluorescent intensity: 1.000±0.104 vs. 0.665±0.088; Aβ 42: 1.000±0.084 vs. 0.600±0.007; Aβ 40: 1.000±0.138 vs. 0.476±0.083), significantly decreased STING protein expression and p-TBK1/TBK1 ratio (STING: 1.000±0.054 vs. 0.468±0.111; p-TBK1/TBK1: 1.000±0.057 vs. 0.598±0.090), and significantly decreased C/EBPβ transcription factor activity (1.000±0.097 vs. 0.445±0.106; P<0.05). (3) Compared with the 3×Tg-AD+eHSD group, the 3×Tg-AD/C/EBPβ +/-+eHSD group had significantly decreased area under the latency curve, significantly increased proportion of time spending in the targeted quadrant, significantly decreased p-tau and tau oligomers, Aβ 42 and Aβ 40 concentrations in the hippocampus (AT8 fluorescent intensity: 1.000±0.160 vs. 0.506±0.065; T22 fluorescent intensity: 1.000±0.127 vs. 0.346±0.048; Aβ 42: 1.000±0.017 vs. 0.510±0.101; Aβ 40: 1.000±0.098 vs. 0.586±0.153), and significantly decreased C/EBPβ protein expression (1.000±0.101 vs. 0.568±0.094; P<0.05). (4) Compared with the Non-Tg/3×Tg-AD+eHSD+DMSO group, the Non-Tg/3×Tg-AD+eHSD+H-151 group had significantly decreased area under the latency curve, significantly increased proportion of time spending in the targeted quadrant, and significantly decreased p-tau and tau oligomers expressions, Aβ 40 concentration in the hippocampus, and the Non-Tg/3×Tg-AD+eHSD+H-151 group, the C/EBPβTg/3×Tg-AD+eHSD+H-151 group had significantly decreased STING protein expression and p-TBK1/TBK1 ratio in the hippocampus ( P<0.05). Compared with the Non-Tg/3×Tg-AD+eHSD+H-151 group, the C/EBPβTg/3×Tg-AD+eHSD+H-151 group had significantly increased area under the latency curve, significantly decreased proportion of time spending in the targeted quadrant, and significantly increased p-tau and tau oligomers expressions, Aβ 40 and Aβ 42 concentration in the hippocampus ( P<0.05). Conclusion:The eHSD aggravates cognitive impairment in 3×Tg-AD mice through activating cGAS-STING-C/EBPβ pathway.

Objective:To explore the efficacy and safety of the combination therapy of lenalidomide and rituximab (R2) for short-cycle maintenance therapy in patients with B-cell non-Hodgkin lymphoma (B-NHL).Methods:A retrospective case series study was conducted. The clinical data of 19 B-NHL patients who received R2 regimen maintenance therapy after achieving complete remission through chemotherapy or autologous hematopoietic stem cell transplantation at Dongguan Kanghua Hospital from February 2018 to January 2024 were collected, and the overall survival (OS), progression-free survival (PFS), adverse reactions, changes in lymphocyte subsets and cytokine levels before and after treatment were analyzed.Results:Among the 19 patients, there were 7 males and 12 females, with a median age [ M ( Q1, Q3)] of 49 (45, 65) years. The median follow-up time was 56 months, ranging from 5 to 77 months. The 1-year OS and PFS rates were 89.2% and 88.9%, respectively. The 2-year and 5-year PFS rates were both 83.2%, and the 2-year and 5-year OS rates were both 88.9%. Common adverse reactions included hematological adverse reactions and infections, with 4 cases (21.1%) experiencing grade 3-4 hematological adverse reactions and 4 cases (21.1%) experiencing infections. There was no statistically significant difference in the levels of lymphocyte subsets (total T cells, helper T cells, regulatory T cells, NK cells, B cells, and CD4/CD8) and cytokines [interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-α, and interferon-γ] before and after treatment (all P > 0.05). Conclusions:The R2 regimen for short-cycle maintenance therapy of B-NHL is effective and well tolerated by patients.

OBJECTIVE To establish refined medication rules for parenteral nutrition （PN） and evaluate its effectiveness. METHODS Refined medication rules for PN were constructed based on drug instructions， relevant guidelines， and expert consensus. Through the pre-approval review system of prescription automatic screening system （PASS）， PN prescription information for inpatients from January to December 2024 （referred to as “post-intervention”） was collected to analyze the post- intervention prescription review status. PN prescription information for inpatients at our hospital from January to December 2023 and January to December 2024 was collected through the medical order review system to evaluate the rationality rates of PN prescriptions. RESULTS The established refined medication rules for PN included system module rules （including nutrients， drug compatibility， PN concentration and osmotic pressure） and custom review rules （covering off-label drug use， drug compatibility， and other drug use conditions）. As of December 2024， the PASS pre-approval review system had established a total of 102 rules， comprising 55 system module rules and 47 custom review rules for PN. After intervention， when comparing with the first quarter of 2024， the number of PN reviewed and intervened by pharmacists decreased， the pharmacist intervention rate dropped， while the rate of physician modifications following pharmacist intervention increased in the fourth quarter. The primary types of irrational prescriptions identified by the system module rules were irrational PN concentration and osmotic pressure. The primary types of irrational prescriptions identified by the custom review rules were off-label drug use （specifically indications for amino acids） and irrational drug incompatibility. In 2024， the number of false-positive tasks and the false-positive rate initially increased and then decreased， while both the number of irrational prescriptions identified through manual review and the false-negative rate showed a declining trend. In 2024， the overall rationality rate after manual review PN refined medication rules for PN medical order review system significantly increased compared to that in 2023 （P＜0.01）. CONCLUSIONS The refined medication rules for PN in our hospital were established successfully， which can reduce the PN-induced risks and significantly improve the rationality of PN prescriptions.