The pharmaceutical industry faces challenges in quality digitization for complex multi-stage processes, especially in small-sample systems. Here, an intelligent quality prediction and diagnostic (IQPD) framework was developed and applied to Tong Ren Tang's Niuhuang Qingxin Pills, utilizing four years of data collected from four production units, covering the entire process from raw materials to finished products. In this framework, a novel path-enhanced double ensemble quality prediction model (PeDGAT) is proposed, which combines a graph attention network and path information to encode inter-unit long-range and sequential dependencies. Additionally, the double ensemble strategy enhances model stability in small samples. Compared to global traditional models, PeDGAT achieves state-of-the-art results, with an average improvement of 13.18% and 87.67% in prediction accuracy and stability on three indicators. Additionally, a more in-depth diagnostic model leveraging grey correlation analysis and expert knowledge reduces reliance on large samples, offering a panoramic view of attribute relationships across units and improving process transparency. Finally, the IQPD framework integrates into a Human-Cyber-Physical system, enabling faster decision-making and real-time quality adjustments for Tong Ren Tang's Niuhuang Qingxin Pills, a product with annual sales exceeding 100 million CNY. This facilitates the transition from experience-driven to data-driven manufacturing.

Ten novel xanthones, garpedunxanthones A-G (1-5, 6a/6b, 7a/7b) and nujiangxanthone Q (8), along with sixteen known analogs (9-24), were isolated from Garcinia pedunculata and G. nujiangensis. Their structures were elucidated through high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) data, comprehensive nuclear magnetic resonance (NMR) spectroscopic analyses, and electronic circular dichroism (ECD) calculations. All compounds without cytotoxicity were assessed for anti-inflammatory properties by measuring the inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 cells. Structure-activity relationships are also discussed. Compounds 7b, 19, and 21 exhibited significant anti-inflammatory activity with IC₅₀ values of 16.44 ± 0.69, 14.28 ± 0.78, and 10.67 ± 3.28 μmol·L^-1, respectively. Enzyme-linked immunosorbent assay (ELISA) demonstrated that compounds 7b, 19, and 21 inhibited the expression of pro-inflammatory cytokines TNF-α and IL-6 in a dose-dependent manner. The inhibitory effect of compound 21 on IL-6 at 20 μmol·L^-1 was comparable to that of the positive control. In network pharmacology studies, potential targets of compounds and inflammation were identified from PharmMapper and GeneCards databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the overlapped targets were intricately associated with major pathogenic processes linked to inflammation, including positive regulation of mitogen-activated protein kinase (MAPK) cascade, protein kinase activity, NO synthase regulator activity, MAPK signaling pathway, and EGFR tyrosine kinase inhibitor resistance.
Xanthones/therapeutic use* ; Garcinia ; Anti-Inflammatory Agents/therapeutic use* ; Plant Preparations/therapeutic use* ; Structure-Activity Relationship ; Nitric Oxide/metabolism* ; RAW 264.7 Cells ; Animals ; Mice ; Enzyme-Linked Immunosorbent Assay ; Mitogen-Activated Protein Kinase Kinases/metabolism* ; Circular Dichroism

Objective:To investigate the efficacy of antiviral therapy and influencing factors of hepatitis B surface antigen(HBsAg) negative conversion for hepatitis B e antigen(HBeAg)-positive chronic hepatitis B(CHB) in children.Methods:The clinical data of 38 children with CHB who received antiviral treatment in Children's Hospital Affiliated to Xi'an Jiaotong University from January 2019 to August 2024 were collected.All patients were treated with interferon alpha monotherapy or combined with nucleoside analogues for 48 weeks.The patients were divided into HBsAg negative group and HBsAg non-negative group according to the therapeutic results at 48 weeks.Multivariate Logistic regression were used to identify influencing factors of HBsAg negative conversion at 48 weeks.The receiver operator characteristic（ROC）curve was used to analyze the predictive value of each factor to HBsAg negative conversion.Results:The alanine aminotransferase normalization rate，hepatitis B virus DNA negative rate，HBeAg negative rate and HBsAg negative rate were 76.3%，94.7%，39.5% and 47.4%，respectively at 48 weeks.There were 18 cases in HBsAg negative group and 20 cases in HBsAg non-negative group.There were statistical significant differences in age and HBsAg decline level at 12 and 24 weeks of antiviral treatment between HBsAg negative group and HBsAg non-negative group（ P<0.05）.Multivariate Logistic regression analysis showed that age and HBsAg decline level at 12 and 24 weeks of antiviral treatment were independent predictors of HBsAg negative conversion at 48 weeks（ OR=0.664，95% CI 0.473-0.932， P=0.018； OR=8.719，95% CI 1.920-39.604， P=0.005； OR=6.182，95% CI 2.083-18.347， P=0.001）.The area under the curve of age and HBsAg decline level at 12 and 24 weeks were 0.737（95% CI 0.576-0.899， P=0.012），0.847（95% CI 0.725-0.969， P<0.001）and 0.939（95% CI 0.811-0.991， P<0.001），respectively.When the age was less than 4.625 years，the sensitivity，specificity，positive predictive value and negative predictive value of HBsAg negative conversion at 48 weeks were 83.3%，65.0%，68.2% and 81.3%，respectively.A decrease in HBsAg level of >1.07 lg IU/mL at 12 weeks of treatment had a sensitivity，specificity，positive predictive value，and negative predictive value of 72.2%，90.0%，86.7%，and 78.3%，respectively，for predicting HBsAg seroclearance at 48 weeks.A reduction in HBsAg of >1.92 lg IU/mL at 24 weeks of treatment showed a sensitivity，specificity，positive predictive value，and negative predictive value of 83.3%，90.0%，88.2%，and 85.7%，respectively，in predicting HBsAg seroclearance at 48 weeks. Conclusion:The children with CHB have a higher rate of HBsAg negative conversion after antiviral therapy at 48 weeks.Age and HBsAg decline level at 12 and 24 weeks of antiviral treatment can serve as early predictors for HBsAg negative conversion in children with CHB.

Objective:This study investigated the expression of C-X-C motif chemokine receptor 3 (CXCR3) on CD45RO? T cells in the peripheral blood of patients with Alzheimer′s disease (AD) and its association with clinical features.Methods:A total of 41 AD patients and 30 age-and sex-matched healthy controls (HCs) were recruited from the Department of Neurology at the Medical Division of PLA General Hospital between September 2022 and March 2024. Flow cytometry was used to quantify CXCR3 expression on CD45RO? T cell subsets in peripheral blood. Dementia severity in AD patients was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Spearman correlation analysis examined the relationship between CD45RO?CXCR3? T cell levels and cognitive function in the AD group. Receiver operating characteristic (ROC) curve analysis determined the predictive utility of CD45RO?CXCR3? T cells for AD, quantified by the area under the curve (AUC).Results:Compared to healthy controls, AD patients exhibited significantly elevated levels of CD8?CD45RO?CXCR3? T cells [17.8% (7.2%, 40.3%) vs. 8.2% (5.1%, 12.3%), Z=-2.59, P<0.05]. However, no significant differences were observed for CD4?CD45RO?CXCR3? T cells, CD4?CD45RO?CXCR3? T cells, or CD8?CD45RO?CXCR3? T cells ( P>0.05). Spearman correlation analysis revealed a negative correlation between CD8?CD45RO?CXCR3? T cell levels and cognitive scores (MMSE: r=-0.72, P<0.05; MoCA: r=-0.70, P<0.05). ROC analysis demonstrated an AUC of 0.81 for CD8?CD45RO?CXCR3? T cells in predicting AD, with a sensitivity of 59.0% and specificity of 93.3%. Conclusions:CXCR3 expression is significantly upregulated on CD8?CD45RO? T cells in AD patients, and its levels correlate with cognitive impairment severity. These findings suggest that CD8?CD45RO?CXCR3? T cells may serve as a potential biomarker for AD diagnosis and progression monitoring.

Childhood primary renal tubular diseases are chronic kidney diseases characterized by impaired renal tubular reabsorption. Primary renal tubular disease has diverse clinical manifestations and lacks of specificity. Laboratory tests are limited，making it prone to missed diagnosis and misdiagnosis. Based on the current knowledge of renal tubular diseases，authors propose early warning signals of renal tubular diseases such as family history of primary tubular diseases，unexplained polyhydramnios during pregnancy，polydipsia，polyuria，delayed growth and development or rickets，decreased muscle strength and tone，unexplained electrolyte disturbance，hyperuricemia，acid-base disturbance，positive urine sugar test，renal tubular proteinuria，urinary imaging examination suggesting kidney stones，calcium deposition，renal cysts and early onset of eye，ear，joint and neuron injury.Meanwhile，some universal management strategies for primary renal tubular disease are proposed，emphasizing the importance of multidisciplinary collaboration，genetic testing and individualized intervention to improve the long-term prognosis of childhood primary renal tubular diseases.

Objective:To construct a updating decision model of medical equipment based on multi-criteria,so as to provide scientific guidance for decision of management departments for medical equipment.Methods:To establish an evaluation index system for updating medical equipment,and evaluate the importance of expert,and transform weight language of expert index into intuitionistic fuzzy numbers,and use the Intuitionistic Fuzzy Weighted Average(IFWA)operator to aggregate qualitative indicators,and construct an initial decision matrix by integrating quantitative data,and apply the Tomadade Decis?o Iterativa Multicritério(TODIM)method to conduct prioritization for medical equipment that was waiting update.Four B-ultrasound equipment that were waiting for update in Peking University First Hospital from January 2023 to December 2023 were selected,and they were labeled respectively as A1,A2,A3 and A4 for priority ranking to conduct update.Results:The obtained comprehensive scores of A1,A2,A3 and A4 were respectively 0.617,0,0.714 and 1.000 through intuitionistic fuzzy theory and TODIM calculations.The priority ranking for updated equipment was ε(a4)＞ε(a3)＞ε(a1)＞ε(a2),indicating that medical equipment A4 was the highest-priority equipment for update.The result was consistent with actual operation that A4 equipment had been scrapped for disposal as scheme in April,2024.Conclusion:The model of updating decision for medical equipment on the basis of the intuitionistic fuzzy TODIM,can effectively avoid the subjectivity of medical institutes in updating equipment and solve the problem of multi-criteria decision-making in updating medical equipment.

Objective:To construct a updating decision model of medical equipment based on multi-criteria,so as to provide scientific guidance for decision of management departments for medical equipment.Methods:To establish an evaluation index system for updating medical equipment,and evaluate the importance of expert,and transform weight language of expert index into intuitionistic fuzzy numbers,and use the Intuitionistic Fuzzy Weighted Average(IFWA)operator to aggregate qualitative indicators,and construct an initial decision matrix by integrating quantitative data,and apply the Tomadade Decis?o Iterativa Multicritério(TODIM)method to conduct prioritization for medical equipment that was waiting update.Four B-ultrasound equipment that were waiting for update in Peking University First Hospital from January 2023 to December 2023 were selected,and they were labeled respectively as A1,A2,A3 and A4 for priority ranking to conduct update.Results:The obtained comprehensive scores of A1,A2,A3 and A4 were respectively 0.617,0,0.714 and 1.000 through intuitionistic fuzzy theory and TODIM calculations.The priority ranking for updated equipment was ε(a4)＞ε(a3)＞ε(a1)＞ε(a2),indicating that medical equipment A4 was the highest-priority equipment for update.The result was consistent with actual operation that A4 equipment had been scrapped for disposal as scheme in April,2024.Conclusion:The model of updating decision for medical equipment on the basis of the intuitionistic fuzzy TODIM,can effectively avoid the subjectivity of medical institutes in updating equipment and solve the problem of multi-criteria decision-making in updating medical equipment.

Objective:To investigate the efficacy of antiviral therapy and influencing factors of hepatitis B surface antigen(HBsAg) negative conversion for hepatitis B e antigen(HBeAg)-positive chronic hepatitis B(CHB) in children.Methods:The clinical data of 38 children with CHB who received antiviral treatment in Children's Hospital Affiliated to Xi'an Jiaotong University from January 2019 to August 2024 were collected.All patients were treated with interferon alpha monotherapy or combined with nucleoside analogues for 48 weeks.The patients were divided into HBsAg negative group and HBsAg non-negative group according to the therapeutic results at 48 weeks.Multivariate Logistic regression were used to identify influencing factors of HBsAg negative conversion at 48 weeks.The receiver operator characteristic（ROC）curve was used to analyze the predictive value of each factor to HBsAg negative conversion.Results:The alanine aminotransferase normalization rate，hepatitis B virus DNA negative rate，HBeAg negative rate and HBsAg negative rate were 76.3%，94.7%，39.5% and 47.4%，respectively at 48 weeks.There were 18 cases in HBsAg negative group and 20 cases in HBsAg non-negative group.There were statistical significant differences in age and HBsAg decline level at 12 and 24 weeks of antiviral treatment between HBsAg negative group and HBsAg non-negative group（ P<0.05）.Multivariate Logistic regression analysis showed that age and HBsAg decline level at 12 and 24 weeks of antiviral treatment were independent predictors of HBsAg negative conversion at 48 weeks（ OR=0.664，95% CI 0.473-0.932， P=0.018； OR=8.719，95% CI 1.920-39.604， P=0.005； OR=6.182，95% CI 2.083-18.347， P=0.001）.The area under the curve of age and HBsAg decline level at 12 and 24 weeks were 0.737（95% CI 0.576-0.899， P=0.012），0.847（95% CI 0.725-0.969， P<0.001）and 0.939（95% CI 0.811-0.991， P<0.001），respectively.When the age was less than 4.625 years，the sensitivity，specificity，positive predictive value and negative predictive value of HBsAg negative conversion at 48 weeks were 83.3%，65.0%，68.2% and 81.3%，respectively.A decrease in HBsAg level of >1.07 lg IU/mL at 12 weeks of treatment had a sensitivity，specificity，positive predictive value，and negative predictive value of 72.2%，90.0%，86.7%，and 78.3%，respectively，for predicting HBsAg seroclearance at 48 weeks.A reduction in HBsAg of >1.92 lg IU/mL at 24 weeks of treatment showed a sensitivity，specificity，positive predictive value，and negative predictive value of 83.3%，90.0%，88.2%，and 85.7%，respectively，in predicting HBsAg seroclearance at 48 weeks. Conclusion:The children with CHB have a higher rate of HBsAg negative conversion after antiviral therapy at 48 weeks.Age and HBsAg decline level at 12 and 24 weeks of antiviral treatment can serve as early predictors for HBsAg negative conversion in children with CHB.

Objective:This study investigated the expression of C-X-C motif chemokine receptor 3 (CXCR3) on CD45RO? T cells in the peripheral blood of patients with Alzheimer′s disease (AD) and its association with clinical features.Methods:A total of 41 AD patients and 30 age-and sex-matched healthy controls (HCs) were recruited from the Department of Neurology at the Medical Division of PLA General Hospital between September 2022 and March 2024. Flow cytometry was used to quantify CXCR3 expression on CD45RO? T cell subsets in peripheral blood. Dementia severity in AD patients was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Spearman correlation analysis examined the relationship between CD45RO?CXCR3? T cell levels and cognitive function in the AD group. Receiver operating characteristic (ROC) curve analysis determined the predictive utility of CD45RO?CXCR3? T cells for AD, quantified by the area under the curve (AUC).Results:Compared to healthy controls, AD patients exhibited significantly elevated levels of CD8?CD45RO?CXCR3? T cells [17.8% (7.2%, 40.3%) vs. 8.2% (5.1%, 12.3%), Z=-2.59, P<0.05]. However, no significant differences were observed for CD4?CD45RO?CXCR3? T cells, CD4?CD45RO?CXCR3? T cells, or CD8?CD45RO?CXCR3? T cells ( P>0.05). Spearman correlation analysis revealed a negative correlation between CD8?CD45RO?CXCR3? T cell levels and cognitive scores (MMSE: r=-0.72, P<0.05; MoCA: r=-0.70, P<0.05). ROC analysis demonstrated an AUC of 0.81 for CD8?CD45RO?CXCR3? T cells in predicting AD, with a sensitivity of 59.0% and specificity of 93.3%. Conclusions:CXCR3 expression is significantly upregulated on CD8?CD45RO? T cells in AD patients, and its levels correlate with cognitive impairment severity. These findings suggest that CD8?CD45RO?CXCR3? T cells may serve as a potential biomarker for AD diagnosis and progression monitoring.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.