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.

Objective: To investigate the characteristics and potential risk factors associated with HIV infection among newly reported HIV positive male student cases in Jiangsu Province from 2023 to 2024, so as to provide evidence for targeted intervention strategies. Methods: Data were obtained from the China CDC Surveillance System on newly reported HIV positive male student cases from 2023 to 2024. A survey was conducted to collect information on demographic characteristics, knowledge of AIDS prevention, education and training history, HIV testing history, behavioral and substance use patterns, and other relevant factors prior to HIV diagnosis among 343 newly reported HIV positive male student cases in Jiangsu Province. Multivariate Logistic regression analysis was used to assess the risk factors of HIV infection among male students. Results: Among the HIV positive male student cases, homosexual behavior accounted for 93.88% of transmission routes, while 10.20% involved heterosexual contact, as well as 4.08% for two sexual hehaviors. Awareness of HIV prevention knowledge was 97.08%, and 66.76% had previously undergone HIV testing. Among the respondents, 10.50% had used rush poppers as enhancers, and 72.30% had received HIV prevention education within the past year. Among students cases with homosexual behavior, the median time from first homosexual contact to HIV diagnosis was ≤2 years, with 54.66% of cases falling into this category; the most common way of finding same sex partners was through social software, accounting for 88.20% of cases, while the proportion of those via "Blued" app reached 87.07% ; the proportion of using condoms every time during sexual activity in the past six months was 12.27%. Among the student cases with homosexual behavior, the results of multiple Logistic regression analysis showed that student cases aged 18 to 24 ( OR =4.52) and >24 ( OR = 19.23 ), without receiving education on HIV prevention in the past year ( OR =1.86), having consistent condom use ( OR =2.73) and not using condoms ( OR =2.12) during the last sexual activity were more likely to had the first same sex sexual activity for more than 3 years before being diagnosed as HIV positive cases (all P <0.05). Student cases who were uncertain about their partner s sexual identity ( OR =0.33), and who primarily identified same sex partners through "other" means ( OR = 0.23 ) were more likely to avoid HIV testing; in contrast, student cases with consistent condom use during the last homosexual encounter ( OR =7.20) was significantly associated with increased likelihood of HIV testing (all P <0.05). Conclusions Newly reported HIV positive male student cases in Jiangsu Province exhibit serious discrepancies between knowledge and practice regarding HIV prevention. Measures are needed to accelerate the optimization of campus based HIV prevention education content and delivery methods. Simultaneously, enhanced management of extracurricular male populations is essential to effectively control the spread of HIV.

Objective To evaluate the short-term effects of comprehensive health management interventions for stroke high-risk population screening on the prevention and treatment of ischemic stroke, and to provide reference and basis for improving and exploring health management and prevention strategies for stroke high-risk population. Methods From 2018 to 2022, 13 community health service centers in Jiading District, Shanghai were selected in the present study. Based on information push platform, stroke risk assessment and health intervention follow-up were conducted for community residents through convenience sampling. The residents were divided into a full course intervention group (intervention group) and a routine intervention group (control group) according to different health intervention measures and forms. The incidence of ischemic stroke in the two groups of survey subjects was tracked within 36 months. Results A total of 52144 subjects were included in the study. The total number of patients in the full course intervention group was 14227, with an incidence density of 577.32/100 000 (556.49/100 000-598.12/100 000), which was lower than that of the conventional intervention group (37 917), with an incidence density of 1 485.47/100 000 (1 464.99/100 000-1 505.94/100 000) (χ²=2490.212, P<0.001). The relative risk of the full course intervention group was 0.39, and the relative risk of stroke risk factors in the full course intervention group from low to high was 0.33, 0.43, 0.45, and 0.49, respectively. The incidence density of males in the full course intervention group was 660.76 (627.46/100 000 - 694.05/100 000), with a relative risk of 0.43, and the incidence density of female patients was 509.71/100 000 (483.37/100 000 - 536.05/100 000), with a relative risk of 0.35. The overall incidence density of the population under 62 years old gourp, 62-75 years old group and over 75 years old group was 197.45/100 000 (173.09/100 000 -221.80/100 000), 608.36/100 000 (580.19/100 000-636.54/100 000), and 1 025.06/100 000 (958.51/100 000-1 091.61/100 000), with relative risks of 0.51, 0.44, and 0.38, respectively. Conclusion Comprehensive health management measures can effectively reduce the short-term risk of ischemic stroke, and should be further promoted and improved to enhance the effectiveness of stroke prevention and control.

BackgroundPain is one of the most common physical symptoms in patients with major depressive disorder （MDD）. The high comorbidity rate of MDD and pain aggravates patients' physical and psychological distress， undermines their treatment adherence， and contributes to poor clinical outcomes， posing a critical challenge for the clinical management of MDD. Anxiety symptoms are strongly associated with the pain severity in patients with MDD， yet the underlying mechanisms of the association remain poorly elucidated. Accumulating evidence have indicated that depressive symptoms and pain vigilance and awareness are involved in the modulation of pain perception. Nevertheless， few studies have incorporated these variables into an integrated analytical framework to clarify their parallel mediating effects on the relationship between anxiety symptoms and pain severity. ObjectiveTo explore the mediating pathways linking anxiety symptoms to pain severity via depressive symptoms and pain vigilance and awareness in patients with MDD， so as to provide insights for precise intervention for MDD accompanied by pain symptoms. MethodsA total of 249 patients who met the diagnostic criteria for MDD specified in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） were recruited from Beijing Huilongguan Hospital from May to September 2025. Hamilton Depression Scale-17 item （HAMD-17）， Hamilton Anxiety Scale （HAMA）， Pain Vigilance and Awareness Questionnaire （PVAQ） and Numerical Rating Scale （NRS） were used for assessment. Partial correlation analyses were performed to examine correlations among these variables. Parallel mediating effects were tested using model 4 of the Process macro for SPSS， with depressive symptoms and pain vigilance and awareness as parallel mediators linking anxiety symptoms to pain severity. ResultsA total of 135 patients （54.22%） reported pain， comprising 59 （43.70%） with mild pain， 43 （31.85%） with moderate pain， and 33 （24.45%） with severe pain. Partial correlation analyses revealed significant positive correlations among HAMD-17， HAMA， PVAQ， and NRS scores in patients with MDD （r=0.198–0.424， P<0.05 or 0.01）. Anxiety symptoms positively predicted pain severity， with a direct effect of 0.128 （95% CI： 0.065–0.190）. Both depressive symptoms and pain vigilance and awareness acted as partial mediators linking anxiety symptoms to pain severity. The indirect effects were 0.057 （95% CI： 0.029–0.089） and 0.042 （95% CI： 0.016–0.079）， accounting for 25.22% and 18.58% of the total effect， respectively. ConclusionIn patients with MDD， anxiety symptoms exert a positive predictive effect on pain severity， which is partially mediated through the parallel roles of depressive symptoms and pain vigilance and awareness.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

Objective:To explore the relationship between early fecal calprotectin (FC) level and the long-term efficacy of infliximab (IFX) in the treatment of Crohn′s disease (CD) and predictive the value.Methods:From January 2018 to December 2023, at the First Affiliated Hospital with Nanjing Medical University, the clinical data of patients with moderate-to-severe CD who received IFX as first-line therapy were retrospectively collected. The main outcomes were clinical and endoscopic remission at week 52 after IFX treatment, and the secondary outcome was clinical response at week 14 after IFX treatment. The predictive value of FC levels at week 0 (at baseline when first administered) and week 14 of treatment was evaluated for the clinical and endoscopic remission at week 52 after IFX treatment. Multivariate logistic regression was performed to investigate the factors predicting endoscopic remission. The optimal cutoff value was calculated, model was established, the data was divided into training set and validation set at a ratio of 7∶3 using the random number table method and the corresponding column chart was drawn. Receiver operating characteristic curve (ROC) and calibration curve were used to evaluate the discrimination and calibration of the model, respectively. Mann-Whitney U test was used for statistical comparison. Results:A total of 165 patients with CD were enrolled, of whom 150 cases (90.9%) achieved clinical response after induction therapy, and 15 cases (9.1%) were primary non-response. Among the 150 patients with clinical response, 112 cases (74.7%) achieved clinical remission at week 52 after treatment, while 38 cases (25.3%) did not achieve clinical remission. Endoscopic evaluation was performed at week 52 after treatment in 139 patients, of whom 54 cases (38.8%) achieved endoscopic remission and 85 cases (61.2%) did not. At week 14 of treatment, there was no statistically significant difference in FC level between the patients achieved and did not achieve clinical response (263.24 (93.96, 675.28) μg/g vs. 556.35 (245.77, 953.56) μg/g, P>0.05). At week 52 after treatment, the FC level of patients who achieved clinical remission was lower than that of patients did not achieve(103.20(44.11, 456.57) μg/g vs. 531.26(222.06, 998.40) μg/g) and the decreased value of FC at week 52 and week 0 after treatment of patients achieved clinical remission was more than that of patients did not achieve clinical remission (443.34 (82.25, 788.95) μg/g vs. 269.91 (-79.20, 522.54) μg/g), and the differences were statistically significant ( U=1 078.00, 2 677.00; P<0.001, =0.018). At week 52 after treatment, the FC level of patients achieved endoscopic remission was lower than that of patients did not achieve endoscopic remission (52.80(31.93, 83.47) μg/g vs. 506.18(217.44, 778.02) μg/g), and the decreased value of FC at week 52 and week 0 after treatment of patients achieved endoscopic remission was more than that of patients did not achieve endoscopic remission (428.85(140.20, 863.60) μg/g vs. 309.61(-62.37, 683.82) μg/g), and the differences were statistically significant ( U=500.00, 2 812.00; P<0.001, =0.025). The FC level at week 14 of treatment could predict the clinical and endoscopic remission at week 52 after treatment (area under the curve (AUC) =0.663, 0.773; 95% confidence interval (95% CI): 0.566 to 0.760, 0.694 to 0.852; P=0.006, <0.001). The optimal cutoff value of FC at week 14 of treatment for predicting endoscopic remission at week 52 after treatment was 246.13 μg/g, with a sensitivity of 0.741 and a specificity of 0.671. The results of multivariate logistic regression analysis revealed that FC ≤ 246.13 μg/g at week 14 of treatment ( OR=4.576, 95% CI: 2.021 to 10.363, P<0.001), baseline albumin ( OR=1.093, 95% CI: 1.006 to 1.188, P=0.035), and baseline platelet-to-lymphocyte ratio (PLR) ( OR=0.995, 95% CI: 0.990 to 1.000, P=0.046) were independent influencing factors of endoscopic remission at week 52 after treatment. A predictive model for endoscopic remission at week 52 after IFX treatment was established based on FC ≤ 246.13 μg/g at week 14 of treatment, baseline albumin and PLR. The results of ROC analysis showed that this model had good discriminative ability, with an AUC of 0.780 (95% CI: 0.700 to 0.878) in the validation set, with a sensitivity of 0.812 and a specificity of 0.760. The results of calibration curve analysis demonstrated that the average absolute error of the prediction model in the validation set was 0.038, and the consistency between the predicted probability and the actual probability was good. Conclusion:FC ≤ 246.13 g/g at week 14 of IFX treatment has good predictive value for endoscopic remission at week 52 after treatment in CD patients.

"Double first-class" universities bear the pressure on competitions in scientific research and talents cultivation. Young faculties at these universities commonly face the stress of tenure-track assessment. Many of them are required to engage in part-time counselor work, leveraging their expertise in the value guidance for the students and providing all-round education. This article outlines the formation and development of the part-time counselor system, as well as the importance and necessity of part-time counselors in "double first-class" universities. Taking preventive medicine major of Fudan University as an example, the practical work of part-time counselors are explained. Finally, the responsibility of part-time counselors, as well as shortcomings and prospects of the construction of the part-time counselor team are summarized based on the major characteristics and cultivation goals of preventive medicine major. In a word, part-time counselors play an important role in guiding students' value formation, addressing psychological and life issues, fostering professional identity, mentoring academic research, and engaging in public health practice. In turn, this work deepens young teachers' appreciation of socialist education and strengthens their sense of nationality at the same time. In the future, it is still necessary to further improve the discovery and cultivation of top-notch innovative talents, promote interdisciplinary exchanges, and strengthen public health practice, etc. Strengthen the all-round capacity building of the team of part-time counselors, and accelerate the cultivation of high-quality interdisciplinary public health leaders who serve Healthy China and have an international perspective are of great significance.