1.Impact of birth weight on the trajectory of blood pressure among primary school students
CUI Chengpeng, YE Siyan, FANG Yanfei, LI Yan, PENG Zeqin, XIAO Yuqing, WU Meng, LIU Qin
Chinese Journal of School Health 2026;47(3):309-313
Objective:
To explore the early effects of birth weight at different gestational ages on blood pressure trajectory among primary school students, so as to provide evidence for incorporating gestational age birth weight into individualized early warning and intervention strategies for childhood hypertension.
Methods:
From May to November 2023, a purposeful sampling method was used to recruit 1 676 students in grade 1-3 from three primary schools in a certain urban district of Chongqing. Follow up assessments were conducted in May 2024(T1), November 2024(T2), and May 2025(T3). General demographic and birth related information were collected via self administered questionnaires, while height, weight and blood pressure were obtained through physical examinations. Linear mixed effects model was used to analyze the associations between birth weight at different gestational ages and blood pressure trajectories.
Results:
During the T1-T3 period, the systolic blood pressure of boys were 98.5 (93.0, 104.5 ),98.5 (93.5, 105.0), and 97.5 (92.5, 103.5)mmHg, respectively, while the diastolic blood pressure were 60.5 (56.5, 65.0), 61.5 ( 57.0 , 65.5), and 60.0 (56.0, 64.0)mmHg, respectively. For girls, the systolic blood pressure were 95.5 (90.0, 102.0),95.5 (90.5, 101.5), and 96.0 (90.5, 101.5)mmHg, respectively, and the diastolic blood pressure were 60.5 (56.0, 64.5 ),61.5 (57.5, 65.5), and 59.5 (56.0, 63.0)mmHg, respectively. Through Friedman test within both boys and girls, diostolic blood pressure were statistically significant across three measurements( χ 2=48.85,81.54,both P <0.01). The proportion of normal blood pressure increased , and the proportion of prehypertension and hypertension decreased with time( χ 2=39.72,25.62,both P < 0.01 ). Linear mixed effects model analysis revealed that after adjusting for age, sex, household income monthly, parental education, family history of hypertension and maternal pregnancy complications, large for gestational age had significantly higher trajectories of systolic ( β = 1.50) and diastolic( β =0.94) blood pressure compared to appropriate for gestational age(both P <0.01).
Conclusion
Large for gestational age is associated with elevated blood pressure trajectories during school age, and it may be considered as an early indicator for individualized screening and intervention for childhood hypertension.
2.Effect and mechanism of action of Biejiajian Pills on a rat model of hepatic fibrosis induced by carbon tetrachloride
Longda WU ; Yuanqin DU ; Yanfei WEI ; Dewen MAO ; Yong LIN ; Lu LU ; Faming SHU
Journal of Clinical Hepatology 2026;42(8):1866-1877
ObjectiveTo investigate the therapeutic effect of Biejiajian Pills on rats with carbon tetrachloride (CCl4)-induced hepatic fibrosis and its mechanism based on the bile acid (BA)-short-chain fatty acid (SCFA) metabolic axis. MethodsThe method of CCl4 induction was used to establish a rat model of hepatic fibrosis, and 32 male Sprague-Dawley rats were randomly divided into control group, model group, Biejiajian Pills group (2.2 g/kg), and silymarin group (43.19 mg/kg), with 8 rats in each group. All rats except those in the control group were given intraperitoneal injection of CCl4 (diluted with corn oil at a ratio of 4∶6, 2 mL/kg) to induce a model of hepatic fibrosis for 8 consecutive weeks, and the rats in the drug administration groups were given the corresponding drug by gavage. An automatic biochemical analyzer was used to measure the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), and albumin (Alb); chloramine-T colorimetry was used to measure the content of hydroxyproline (HYP) in liver tissue; HE staining and Masson staining were used to observe liver histopathological changes; UPLC-MS/MS and GC-MS were used to measure the levels of BAs and SCFAs. The Shapiro-Wilk test and the Levene test were performed for all data to determine normality and homogeneity of variance; a one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups; the Kruskal-Wallis H test was used for comparison of Ishak score between groups, and the Dunn’s test was used for further comparison between two groups. The Benjamini-Hochberg method was used for multiple comparison correction in the screening of differentially expressed metabolites in metabolomics data. The variable importance in projection (VIP) values were obtained in combination with the orthogonal partial least squares-discriminant analysis (OPLS-DA) model, and metabolites with VIP>1 and P<0.05 were selected as significantly differentially expressed metabolites between groups. The robustness of the OPLS-DA model was evaluated through 200 permutation tests, and the main parameters of the model were reported, including the interpretation rate of the model for categorical variables (R2Y) and the predictive ability of the model (Q2). A Spearman’s rank correlation analysis was performed. ResultsThe results of staining showed ordered arrangement of hepatocytes in the Biejiajian Pills group, with significant alleviation of inflammatory cell infiltration and collagen fiber deposition. Compared with the control group, the model group had significant increases in the serum levels of TBil and HYP and a significant reduction in the serum level of Alb (all P<0.05). Compared with the control group, the Biejiajian Pills group had significant increases in the serum levels of AST, ALT, TBil, and HYP and a significant reduction in the serum level of Alb (all P<0.05), and the silymarin group had significant increases in the serum levels of ALT, TBil, and HYP and a significant reduction in the serum level of Alb (all P<0.05). Compared with the model group, the Biejiajian Pills group had significant reductions in the serum levels of ALT, AST, TBil, and HYP (all P<0.05), and the silymarin group had significant reductions in the serum levels of ALT, TBil, HYP, and AST and a significant increase in the serum level of Alb (all P<0.05). Mechanism studies showed that compared with the control group, the model group had significant reductions in the levels of taurolithocholic acid, tauro-α-muricholic acid, taurocholic acid, glycodeoxycholic acid, taurohyocholic acid, chenodeoxycholic acid, glycohyodeoxycholic acid, 7,12-diketolithocholic acid, taurochenodeoxycholic acid, and glycochenodeoxycholic acid and significant increases in the levels of hyodeoxycholic acid, norcholic acid, β-muricholic acid, and cholic acid (all P<0.05). Compared with the model group, the Biejiajian Pills group had significant increases in the levels of the protective BAs taurolithocholic acid, chenodeoxycholic acid, taurocholic acid, taurohyocholic acid, and taurodeoxycholic acid and significant reductions in the levels of tauro-α-muricholic acid, tauro-β-muricholic acid, taurohyodeoxycholic acid+tauroursodeoxycholic acid, α-muricholic acid, glycoursodeoxycholic acid, and norcholic acid (alll P<0.05). As for SCFAs, compared with the model group, the Biejiajian Pills group had significant increases in the levels of acetic acid, propionic acid, isobutyric acid, butyric acid, isopentanoic acid, pentanoic acid, and hexanoic acid (all P<0.05). Compared with the model group, the silymarin group had significant reductions in the levels of taurolithocholic acid, tauro-α-muricholic acid, norcholic acid, glycocholic acid, deoxycholic acid, tauro-β-muricholic acid, taurodeoxycholic acid, taurohyodeoxycholic acid+tauroursodeoxycholic acid, and α-muricholic acid and significant increases in the levels of taurocholic acid and chenodeoxycholic acid, as well as significant increases in the levels of the SCFAs acetic acid, propionic acid, pentanoic acid, and hexanoic acid (all P<0.05). The correlation analysis showed that the metabolism of BAs and SCFAs was correlated with the changes in serum indicators. ConclusionBiejiajian Pills can alleviate CCl4-induced hepatic fibrosis in rats by regulating the BA/SCFA metabolic axis.
3.Development of a training content framework for hospice volunteers based on competency model
Qiaozhen XIANG ; Linye WU ; Shulan YANG ; Xichen CHAI ; Yanfei XIA ; Yanfang LI ; Yilong YANG
Chinese Journal of General Practitioners 2025;24(4):405-413
Objective:To develop a training content framework for hospice volunteers based on the competency model.Methods:This was a qualitative study. A draft of the training content framwork for hospice volunteers was first formed according to results of literature review and qualitative interviews based on the competency model. From December 2023 to March 2024, two rounds of Delphi consultation with 16 experts were conducted to develop the final version of the system, and the weights of each indicator were determined with analytic hierarchy process.Results:Among the 14 consulting experts who completed two rounds of consultation, including 10 females, all held intermediate or above professional titles, and their working years ranged from 10 to 34 years, covering fields of hospice care, nursing management, clinical nursing and nursing education. In two rounds of consultation the expert positive coefficient was 14/16 and 14/14, the expert authority coefficient was 0.882 and 0.893, and the Kendall coordination coefficient of all indicators was 0.109 and 0.161 ( P<0.01), the coefficient of variation was 0-0.31 and 0-0.19, respectively. The final version of the system consisted of 3 first-level indicators, 7 second-level indicators, 20 third-level indicators, and 55 specific training contents. The three first-level indicators were knowledge, skill, role and value, and the weight coefficients were 0.335, 0.313 and 0.352, respectively. Each judgment matrix was consistent. Conclusions:A training content system for hospice care volunteers has been developed in this study, which may be used for medical institutions and organizations to train hospice care volunteers.
4.Trajectory of intrinsic capacity and association with daily life ability in people aged 50 years and over in Shanghai
Jiaqi WANG ; Yanfei GUO ; Yan SHI ; Shuangyuan SUN ; Jiamin CAO ; Anli JIANG ; Yujun DONG ; Ye RUAN ; Fan WU
Chinese Journal of Epidemiology 2025;46(7):1209-1216
Objective:To identify the change trajectory of intrinsic capacity in people aged ≥50 years in Shanghai and explore the impact of intrinsic capacity trajectory change on overall function and dalily life activities in this population.Methods:The longitudinal data from round 1 to 3 Study of Global Ageing and Adult Health in Shanghai were used. The total intrinsic ability scores from five dimensions of cognition, psychology, sensory, vitality and locomotion were calculated. The censored normal model of group-based trajectory was used to identify the trajectory of intrinsic capacity change over time. Linear regression model and multivariate logistic regression model were used to analyse the effects of different levels intrinsic capacity trajectory on the scores of the WHO Disability Assessment Schedule (WHODAS), the activity of daily living (ADL) and the instrumental activities of daily living (IADL).Results:A total of 2 302 study participants aged ≥50 years with 3 round complete data were included in this study, and 3 levels of intrinsic capacity trajectory were identified, low-level trajectory (9.3%), medium-level trajectory (41.7%), and high-level trajectory (49.0%). Compared with the high-level group, the medium-level and low-level groups had higher WHODAS scores, which increased by 3.578 (95% CI: 2.028-5.129) and 12.620 (95% CI: 9.951-15.289), respectively, and those with more severe disability and those in the low-level group were at higher risk for severe difficulty in ADLs ( OR=12.450, 95% CI: 4.310-35.966) and IADLs ( OR=5.479, 95% CI: 1.311-22.904). Conclusions:Heterogeneity in trajectory of intrinsic capacity exists in people aged ≥50 years in Shanghai. Middle-aged and elderly people with low initial level and rapid decline trajectory of intrinsic capacity are at greater risk for the decline of daily life ability and the increase of disability. It is necessary to strengthen the long-term dynamic monitoring and evaluation of the change trajectory of intrinsic capacity in this population.
5.A case of ulcerative colitis complicated with bullous pemphigoid
Yuhui GAO ; Yanfei ZHAN ; Xiaohong DANG ; Jingyu REN ; Hongxia HE ; Lina WU ; Linglin TIAN
Chinese Journal of Inflammatory Bowel Diseases 2025;09(5):436-437
Extraintestinal manifestations (EIM) of inflammatory bowel disease (IBD) may affect multiple organ systems, with approximately 50% of IBD patients presenting with at least one EIM during the course of their disease, with cutaneous involvement being particularly common. Cutaneous manifestations can present in various forms. This paper reports a case of ulcerative colitis (UC) complicated with bullous pemphigoid (BP), aiming to enhance clinicians' awareness of skin lesions associated with UC.
6.Molecular Mechanisms of Huangjing Zanyu Capsule in Treating Oligoasthenospermia:A Study Based on AMPK-Mediated Mitophagy
Yuan GAO ; Yiyang GUO ; Mohan WU ; Yanfei ZHENG
Journal of Sichuan University (Medical Sciences) 2025;56(1):74-82
Objective To investigate the molecular mechanism of Huangjing Zanyu Capsule(HJZY),a new class-Ⅲ traditional Chinese medicine for the treatment of male infertility developed by Wang Qi,an academician of the Chinese Academy of Engineering,based on AMPK-mediated mitophagy in the treatment of oligoasthenospermia.Methods Acrolein(ACR)was used to treat GC-2spd(ts)mouse spermatocytes to establish a cell model of oligoasthenospermia.The optimal ACR concentration and exposure time for subsequent modeling were determined by CCK8 cell viability assay.After successful modeling,the cells were cultured in complete medium containing different concentrations of HJZY.Then,cell viability was assessed by CCK8 assay after 24 hours,and the subsequent treatment concentration was determined based on the cell viability.After the GC-2spd cells adhered to the wall,they were divided into a normal control(NC)group,a modeling group,and an ACR+HJZY treatment group.The effect of HJZY on mitophagy was observed by confocal fluorescence microscopy.The three groups of cells were transfected with siRNA-NC and siRNA-AMPK,respectively,and divided into six groups,including siRNA-NC+control,siRNA-NC+ACR,siRNA-NC+ACR+HJZY,siRNA-AMPK+control,siRNA-AMPK+ACR,and siRNA-AMPK+ACR+HJZY groups.Western blot was performed to validate the regulatory effect of HJZY on mitophagy-related proteins,such as p-AMPK,LC3B,P62,PINK1,Parkin,TBK1,and ULK1,which were all proteins mediated by AMPK.Results Through the cell viability assay,34 μmol/L was selected as the the modeling concentration of ACR,and 20 minutes was selected as the modeling time The treatment concentration of HJZY was 160 μmol/L.Confocal fluorescence microscopy showed that HJZY had,to a certain degree,a positive regulatory effect on the mitochondrial membrane potential of damaged spermatogenic cells.The mitochondrial membrane potential of the model group decreased significantly compared with that of the NC group.After exposure to treatment,the cell membrane potential of the ACR+HJZY treatment group increased compared with that of the model group,and the difference was statistically significant(P<0.05).Western blot results showed that the expression levels of p-AMPK/AMPK and PINK1 proteins in the siRNA-NC+ACR group were significantly lower than those in the siRNA-NC+control group(P<0.001).The level of Parkin protein in the siRNA-NC+ACR group was lower than that in the siRNA-NC+control group,but the difference was not statistically significant.After the administration of HJZY,the levels of these 3 proteins increased,and those in the siRNA-NC+ACR+HJZY group were higher than those in the siRNA-NC+ACR group(P<0.001).The expression levels of LC3B,P62,TBK1,and ULK1 proteins in the siRNA-NC+ACR group were higher than those in the siRNA-NC+control group(P<0.01),and those in the siRNA-NC+ACR+HJZY group were lower than those in the siRNA-NC+ACR group(P<0.05).After transfection with the gene-silencing siRNA-AMPK,the expression levels of p-AMPK/AMPK,PINK1,and Parkin proteins in the siRNA-AMPK+ACR group were lower than those in the siRNA-AMPK+control group(P<0.01).After the administration of HJZY,there was no significant difference in the levels of these three proteins between the siRNA-AMPK+ACR+HJZY group and the siRNA-AMPK+ACR group.The expression level of LC3B protein in the siRNA-AMPK+ACR+HJZY group was still lower than that in the siRNA-AMPK+ACR group(P<0.01).There was no significant difference in the levels of P62,TBK1,and ULK1 proteins between the siRNA-AMPK+ACR+HJZY group and the siRNA-AMPK+ACR group.Compared with the siRNA-NC+control group,the siRNA-AMPK+control group showed significantly decreased expression levels of p-AMPK/AMPK,ULK1,and TBK1 proteins(P<0.001),decreased expression of PINK1 protein(P<0.05),and increased expression of P62 protein(P<0.001).Compared with the siRNA-NC+ACR group,the siRNA-AMPK+ACR group showed decreased expression of TBK1 protein(P<0.001),decreased expression of LC3B protein(P<0.01),and decreased expression of ULK1 protein(P<0.05).The expression levels of PINK1 and Parkin proteins in the siRNA-AMPK+ACR group were lower than those in the siRNA-NC+ACR group,but the difference was not statistically significant.Compared with the siRNA-NC+ACR+HJZY group,the siRNA-AMPK+ACR+HJZY group showed decreased expression of p-AMPK/AMPK,PINK1,and Parkin proteins(P<0.05),decreased expression of LC3B protein(P<0.01),and increased expression of P62 protein(P<0.001).There was no significant difference in the levels of TBK1 and ULK1 proteins between the siRNA-AMPK+ACR+HJZY group and the siRNA-NC+ACR+HJZY group.Conclusion HJZY may exert its therapeutic effect on oligoasthenospermia by regulating AMPK-mediated mitophagy.
7.Total alkaloids of Cocculus orbiculatus attenuate ulcerative colitis in mice via PINK1/parkin mitophagy pathway
Qiling JIANG ; Yanfei XU ; Sha YANG ; Pengrui ZHANG ; Qiannan DONG ; Hao WU ; Xiao KANG
Chinese Journal of Pathophysiology 2025;41(10):2001-2008
AIM:To investigate whether total alkaloids of Cocculus orbiculatus(COTA)attenuate ulcerative colitis(UC)in mice via PINK1/parkin mitophagy pathway.METHODS:Sixty C57BL/6 mice were randomly divided into normal control group,model group,positive drug mesalazine group,and low-,medium-and high-dose(0.162,0.324 and 0.486 g/kg)COTA groups,with 10 mice in each group.Except for normal control group,the mice in all groups were given free access to 3%dextran sulfate sodium(DSS)solution for 7 consecutive days to establish a UC model in mice,and were then treated with COTA or mesalazine via oral gavage.The general condition of the mice was observed,and the colon length and disease activity index(DAI)score were determined.Colon histopathological damage was observed by HE staining.The serum levels of interleukin-1β(IL-1β),IL-6 and tumor necrosis factor-α(TNF-α)were detected by ELISA.The pro-tein levels of PINK1,parkin,microtubule-associated protein 1 light chain 3(LC3),P62 and beclin-1 in colon tissues were determined by Western blot.The protein expression of LC3 and parkin was detected by immunofluorescence.RE-SULTS:Compared with normal control group,the mice in model group showed varying degrees of soft stools or bloody stools,decreased body weight(P<0.05),increased DAI score,shortened colon length(P<0.05),and obvious pathologi-cal damage in the colon tissue.The serum levels of IL-1β,IL-6 and TNF-α were elevated(P<0.05).The protein levels of parkin,PINK1,LC3-II and beclin-1 were significantly decreased(P<0.05),while P62 protein expression was in-creased(P<0.05).Immunofluorescence showed a small number of autophagosomes in the colon tissue.In contrast,com-pared with model group,the mice in total alkaloids of Cocculus orbiculatus groups exhibited increased body weight(P<0.05),decreased DAI score,increased colon length(P<0.05),and reduced levels of IL-1β,IL-6 and TNF-α(P<0.05).The protein levels of parkin,PINK1,LC3 and beclin-1 were elevated(P<0.05),while P62 expression was re-duced(P<0.05),with numerous autophagosomes visible in the colon tissue via immunofluorescence.CONCLUSION:Total alkaloids of Cocculus orbiculatus can enhance the expression of mitophagy-related proteins PINK1,parkin,LC3 and beclin-1,activate mitophagy,and reduce the expression of inflammatory factors,thereby attenuating the inflammatory re-sponse in the colon mucosa of DSS-induced UC mice.
8.Epidemiological characteristics and influencing factors of SARS-CoV-2 reinfection in community populations in Xuhui District, Shanghai
Huiting WANG ; Yanfei GUO ; Chen CHEN ; Junhong YUE ; Qingqing JIA ; Fei WU ; Yanlu YIN ; Jiajie ZANG ; Fan WU
Shanghai Journal of Preventive Medicine 2025;37(10):803-812
ObjectiveTo analyze the epidemiological characteristics and influencing factors of SARS-CoV-2 reinfection by conducting follow-up investigations among community residents who experienced their first SARS-CoV-2 infection between March and June 2022, so as to provide a scientific basis for predicting future epidemic trends and adjusting prevention and control strategies. MethodsA cohort study was conducted in Xuhui District, Shanghai. A total of 1 208 individuals with a documented primary SARS-CoV-2 infection between March and June 2022 were enrolled and followed-up longitudinally. Data were collected using structured questionnaire surveys to assess the reinfection rate, incidence density, and clinical manifestations of SARS-CoV-2 reinfection. A logistic regression model was used to analyze the influencing factors of SARS-CoV-2 reinfection. ResultsA total of 497 SARS-CoV-2 reinfection cases were observed among the 1 208 research subjects, with a reinfection rate of 41.14% and an incidence density of 0.63 cases per 1 000 person-days. The cumulative reinfection rates at 6, 9, 12, 15, and 18 months following the initial infection were 0.08%, 15.31%, 19.04%, 33.53%, and 38.25%, respectively. Compared with the primary infection, reinfection was more likely to be symptomatic, with a greater severity of fever, dry cough, sore throat, and runny nose. Being female, younger age, and symptom duration ≥7 days during the primary infection were identified as influencing factors for SARS-CoV-2 reinfection, while a higher socioeconomic status can reduce the risk of SARS-CoV-2 reinfection. ConclusionSARS-CoV-2 reinfection is relatively common and often symptomatic. Age, gender, income level, and the duration of symptoms during the primary infection are identified as infuencing factors for SARS-CoV-2 reinfection. Continuous monitoring of reinfection in the population is recommended, along with the development of effective strategies to mitigate the impact of reinfection.
9.Exploration of emergency airway opening method for dyspnea caused by tumor related cervical tracheal stenosis
Jing WU ; Yanfei LIAO ; Yehai LIU
Chinese Archives of Otolaryngology-Head and Neck Surgery 2025;32(2):121-124
OBJECTIVE To explore emergency airway opening methods for patients with dyspnea caused by tumor related cervical tracheal stenosis,and summarize safe and effective emergency management methods for such patients.METHODS Retrospectively collect cases of dyspnea caused by tumor invasion or wrapping around the cervical trachea treated in the First Affiliated Hospital of Anhui Medical University between January 2012 and December 2023,analyze the process or method of emergency airway opening,and summarize the safe and effective airway opening methods for such patients.RESULTS A total of 31 cases were collected,including 25 cases of thyroid malignant tumors invading the cervical trachea(18 cases of differentiated thyroid cancer,5 cases of thyroid lymphoma,1 case of undifferentiated cancer,and 1 case of medullary cancer),3 cases of cervical tracheal recurrence after laryngeal cancer surgery,2 cases of primary tumors in the cervical trachea,1 case of cervical esophageal cancer,24 cases of grade II dyspnea upon admission,6 cases of grade III dyspnea,and 1 case of grade IV dyspnea.The methods of airway opening are as follows:20 cases underwent tumor resection and tracheotomy under anesthesia intubation and general anesthesia,6 cases underwent longitudinal downward tracheostomy with the larynx as the landmark,2 cases underwent midline tumor resection with the chin and sternum as the landmark to expose the trachea,2 cases underwent emergency tracheotomy with extracorporeal membrane oxygenation(ECMO)support,and 1 case underwent tracheotomy with extracorporeal circulation machine support.All patients successfully opened their airways without serious complications such as major bleeding,asphyxia,or cardiovascular and cerebrovascular accidents.CONCLUSION For patients with tumor induced cervical tracheal stenosis that is difficult to expose the trachea using conventional methods and requires emergency airway opening,the anesthesiology department can first evaluate whether a small tracheal tube can be inserted for general anesthesia before tracheotomy.If intubation is difficult,the airway can be opened by longitudinally splitting the cricoid cartilage or the anterior wall of the trachea,marked by the larynx.If the larynx is covered or wrapped by tumors and cannot be exposed,the midline marked by the chin and suprasternal fossa can be used to remove a portion of the tumor and expose the trachea,followed by longitudinally splitting the anterior wall of the trachea to open the airway.If the above methods are difficult to operate,it is feasible to remove the tumor under general anesthesia with extracorporeal circulation or ECMO support,expose the trachea,and open the airway.
10.AI-integrated IQPD framework of quality prediction and diagnostics in small-sample multi-unit pharmaceutical manufacturing: Advancing from experience-driven to data-driven manufacturing.
Kaiyi WANG ; Xinhai CHEN ; Nan LI ; Huimin FENG ; Xiaoyi LIU ; Yifei WANG ; Yanfei WU ; Yufeng GUO ; Shuoshuo XU ; Lu YAO ; Zhaohua ZHANG ; Jun JIA ; Zhishu TANG ; Zhisheng WU
Acta Pharmaceutica Sinica B 2025;15(8):4193-4209
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.


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