1.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.
2.Comparative Study of Community-Based Management Models of Schizophrenia at Home and Abroad
Zhaohua CHEN ; Xujun FENG ; Yuan SHI ; Lu TAN ; Xiangdong TANG
Journal of Sichuan University (Medical Sciences) 2025;56(4):1152-1159
Schizophrenia,a severe mental illness characterized by high disability and chronicity,imposes a heavy disease burden on society and patients in China.Community-based management plays a crucial role in the long-term and comprehensive management of patients with schizophrenia.Through years of exploration,community-based management models—primarily focused on case management,assertive community treatment(ACT),and crisis intervention—have proven beneficial to the overall recovery of patients.However,notable differences exist in the implementation of these models between domestic and international practices.Given this context,we systematically analyze domestic and international research to examine the characteristics of different management models and the causes of the differences.Based on this analysis,we propose targeted recommendations for improving community-based management of schizophrenia in China.Regarding case management,a tiered approach should be adopted according to regional economic conditions and resource availability to optimize the efficiency of resource allocation.For ACT,we suggest developing a family-centered integrated intervention framework adapted to China's specific context.Finally,regarding crisis intervention,a collaborative family-community-police response mechanism should be established,complemented by enhanced professional training and streamlined referral procedures.We advocate enhancing resource allocation and theoretical research,along with broader involvement of all sectors of society,to jointly optimize the community-based management model for schizophrenia in China.
3.Application of Activity-Based Costing in Hospital Cost Management under the Reform of Medical Insurance Payment Mode
Zhaohua TANG ; Yong XUE ; Jie ZHU
Chinese Health Economics 2024;43(12):110-114
Objective:To explore the application value of Activity-Based Costing (ABC) in hospital cost management under the reform of medical insurance payment mode. Methods:Hospital cost management scheme based on ABC was constructed. The application differences between traditional cost method and ABC were compared and analyzed to determine application advantages of ABC in hospital cost management compared with traditional costing method under the reform of medical insurance payment mode. Taking hospital cost management based on activity-based costing was proposed under the reform of medical insurance payment mode. Results:According to analysis,the cost by traditional costing method was 1731.8173 million yuan,and the cost by ABC was 1925.1388 million yuan,193.3215 million yuan more than that of the former,and the difference rate was 11.16%. The items that gave rise to the differences were mainly due to the fact that the cost of personnel and sanitary materials in the operation cost method were 54.371200 million yuan and 68.810200 million yuan more than the traditional cost method,and that fixed assets and depreciation,intangible assets and amortization,and utilities and property costs were 16.140600 million yuan and 24.217100 million yuan less than the traditional cost method. Conclusion:Compared with traditional costing method,application of ABC in hospital cost management under the reform of medical insurance payment mode is more advanced. It can comprehensively analyze cost compositions and benefits in different projects and medical services at the project level,and thus provide feasible reference basis for promoting hospital cost fine management scheme.
4.Study on risk factors for coma in patients with hypoglycemia
Quanhong LIN ; Yaowei XU ; Yuzhuo LI ; Lebai LIU ; Shifan TANG ; Xiaowan LIN ; Zhaohua XIN
Chinese Journal of Emergency Medicine 2024;33(9):1273-1280
Objective:To investigate the incidence and risk factors of coma in patients with hypoglycemia (≤3.9 mmol/L).Methods:A retrospective study was conducted. Patients aged 20 years and older with blood glucose levels ≤3.9 mmol/L, and measured by emergency physicians from January 2020 to December 2022 were collected. Baseline patient data, clinical values collected on-site, and treatment outcomes were analyzed. The Glasgow Coma Scale (GCS) was used to determine if patients were comatose, with GCS ≤8 classified as the coma group and GCS >8 as the non-coma group. Further analysis was conducted on the resuscitated coma group to identify factors affecting patient recovery. Patients were divided into eight age groups, seven time periods within 24 h, and six blood glucose level groups to calculate the incidence of coma. A multivariate logistic regression model was constructed to analyze independent risk factors for coma in hypoglycemic patients.Results:A total of 754 patients with blood glucose levels ≤3.9 mmol/L were collected, with 425 cases of coma and 329 non-coma cases, resulting in a coma probability of 56.37% (95% CI: 52.82%-59.91%). Patients in the coma group were older ( P<0.001) and had a higher prevalence of diabetes compared to the non-coma group (82.12% vs. 67.78%, P<0.001). The age of all patients was (73.05±15.20) years, with the 61-90 years age groups being the most prone to hypoglycemia and coma. In terms of time distribution, the high-incidence periods for hypoglycemia and coma were 0-6 o’clock, 6-9 o’clock, and 14-18 o’clock. The primary causes of hypoglycemia included reduced energy intake after insulin injection (12.07%), improper use of insulin (6.37%), and reduced energy intake (6.23%), with 71.09% of cases having unknown causes. Additionally, 18.44% of patients used insulin before the onset of hypoglycemia, with a higher proportion in the coma group compared to the non-coma group (22.12% vs. 13.68%, P=0.003). The initial blood glucose level of all patients was (2.13±0.85) mmol/L, with lower levels observed in the coma group compared to the non-coma group ( P<0.001). The probabilities of coma occurrence corresponding to blood glucose levels were: 1.1-1.5 mmol/L (72.97%), 1.6-2.0 mmol/L (68.90%), 2.1-2.5 mmol/L (54.10%), 2.6-3.0 mmol/L (38.20%), 3.1-3.5 mmol/L (37.50%), and 3.6-3.9 mmol/L (19.40%). Multivariate logistic regression analysis indicated that age ( OR=1.021, 95% CI: 1.010-1.033, P<0.001), insulin use before onset ( OR=1.948, 95% CI: 1.142-3.323, P=0.014), and blood glucose concentration ( OR=0.426, 95% CI: 0.347-0.522, P<0.001) were independent predictors of coma in hypoglycemic patients. The investigation revealed that after intravenous injection of 50% glucose solution, 215 of 425 coma patients regained consciousness (50.58%), and the recovery time was (18.43±9.09) min. Patients in the recovery group were younger and had lower initial blood glucose levels compared to the non-recovery group (both P<0.05), while recovery group re-measured blood glucose levels were higher than those in the non-recovery group ( P=0.002). Conclusions:The probability of coma in hypoglycemic patients was high, with insulin use being a common trigger. Proper use of insulin is essential to prevent hypoglycemia and coma.
5.Mechanism of action of Wuzi Yanzong pill in the treatment of oligoasthenozoospermia in rats determined via serum metabolomics
Zhenru Shen ; Zhaohua Zhang ; Kejin Tong ; Chunrui Wang ; Shuaiqiang Wang ; Ping Zhao ; Meng Gu ; Jingjing Hu ; Yibo Tang ; Zhenquan Liu
Journal of Traditional Chinese Medical Sciences 2024;11(2):180-190
Objective:
To investigate the mechanism of action of Wuzi Yanzong pill (WYP) in rats with oligoasthenozoospermia (OAZ) via metabolomics and to provide a possible basis for improving this WYP-based treatment.
Methods:
A rat model of OAZ was established by treating male Sprague–Dawley rats with glucosides from Tripterygium wilfordii Hook. F. Seventy-two rats were randomly divided into six groups: control, L-carnitine (positive control), model, and low-, medium-, and high-dose WYP groups. Rats in the experimental groups were treated with WYP for 4 weeks. At the end of the treatment period, sperm cell quality (density, motility, and viability) was assessed using a semen analysis system, mitochondrial membrane potential (MMP) was assessed using flow cytometry, and testicular injury was assessed using hematoxylin and eosin staining to validate the therapeutic effect of WYP in OAZ. Further, serum metabolomics-based analysis was performed using high-performance liquid chromatography-mass spectrometry to identify differential metabolic pathways and possible mechanisms of action of WYP in OAZ treatment.
Results:
A rat model of OAZ was considered successfully-established after comparing the quality of spermatozoa in the model group to that in the control group. WYP-M and WYP-H treatments significantly improved sperm cell density, motility, and viability compared with those in the model group (all P < .05). Compared with the model group, both WYP-M and WYP-H treatments increased MMP values (P = .006 and P = .021 respectively), while there was no significant difference in the L-carnitine group. L-carnitine and WYP administration reversed damage to the testes to varying degrees compared with that in the model group. Further, 44 differential metabolites and four metabolic pathways, especially autophagy pathway, related to OAZ were identified via metabolomics.
Conclusions
WYP improves sperm cell quality and MMP in OAZ primarily via autophagy regulation. These findings can be employed to improve the efficacy of WYP in humans.
6.Application of Activity-Based Costing in Hospital Cost Management under the Reform of Medical Insurance Payment Mode
Zhaohua TANG ; Yong XUE ; Jie ZHU
Chinese Health Economics 2024;43(12):110-114
Objective:To explore the application value of Activity-Based Costing (ABC) in hospital cost management under the reform of medical insurance payment mode. Methods:Hospital cost management scheme based on ABC was constructed. The application differences between traditional cost method and ABC were compared and analyzed to determine application advantages of ABC in hospital cost management compared with traditional costing method under the reform of medical insurance payment mode. Taking hospital cost management based on activity-based costing was proposed under the reform of medical insurance payment mode. Results:According to analysis,the cost by traditional costing method was 1731.8173 million yuan,and the cost by ABC was 1925.1388 million yuan,193.3215 million yuan more than that of the former,and the difference rate was 11.16%. The items that gave rise to the differences were mainly due to the fact that the cost of personnel and sanitary materials in the operation cost method were 54.371200 million yuan and 68.810200 million yuan more than the traditional cost method,and that fixed assets and depreciation,intangible assets and amortization,and utilities and property costs were 16.140600 million yuan and 24.217100 million yuan less than the traditional cost method. Conclusion:Compared with traditional costing method,application of ABC in hospital cost management under the reform of medical insurance payment mode is more advanced. It can comprehensively analyze cost compositions and benefits in different projects and medical services at the project level,and thus provide feasible reference basis for promoting hospital cost fine management scheme.
7.Simple model construction of arteriovenous fistula classification in maintenance hemodialysis patients
Zhaohua ZOU ; Wei QING ; Liqun TANG ; Zhen ZHANG ; Maocai ZHU
Chinese Journal of Practical Nursing 2023;39(5):374-378
Objective:To construct a simple model of arteriovenous fistula classification,and to achieve the classification of arteriovenous fistula in hemodialysis patients.Methods:The study was a retrospective analysis, a total of 304 hemodialysis patients with internal fistula in People′s Hospital of Deyang City from January 2016 to January 2021 were selected by convenience sampling method,depending on whether the internal fistula was dysfunctional, patients were divided into 64 in the internal fistula failure group and 240 in the internal fistula patency group. Independent influence factors and their regression coefficient were obtained by single-factor analysis and logistic regression analysis, The risk score formula was established based on the regression coefficient to form a simple model of internal fistula classification.The model was evaluated by receiver operating characteristic curve and the scoring criteria for internal fistula classification was determined.Results:Logistic regression analysis showed that diabetes mellitus, hypotension, age≥60 years old, compression time≥30 min, blood phosphorus>1.78 mmol/L, triglyceride>1.71 mmol/L and fibrinogen>4 g/L were independent influencing factors of internal fistula failure (all P<0.05).The area under the receiver operating characteristic curve was 0.858(95% CI 0.789-0.928, P<0.01), and the best critical value of the internal fistula classification was 7.5, the sensitivity was 80.4% and the specificity was 84.8%. Conclusions:By obtaining the predictors of internal fistula failure, conducted the risk score, and constructed a simple model of internal fistula classification, which can effectively predicted the risk of internal fistula failure. It is conducive to the implementation of internal fistula classification management and the puncture of corresponding grade, to ensure the pathway safety of patients.
8.Blocking ERK signaling pathway lowers MMP-9 expression to alleviate brain edema after traumatic brain injury in rats.
Zhaohua TANG ; Wentao WANG ; Zili LIU ; Xiaochuan SUN ; Zhengbu LIAO ; Feilan CHEN ; Guangyuan JIANG ; Gang HUO
Journal of Zhejiang University. Medical sciences 2020;40(7):1018-1022
OBJECTIVE:
To investigate the effects of blocking the activation of ERK pathway on the expression of matrix metalloproteinase-9 (MMP-9) and the formation of cerebral edema in SD rats after brain injury.
METHODS:
Ninety SD rats were randomly divided into 3 equal groups, including a sham-operated group, modified Feeney's traumatic brain injury model group, and ERK inhibition group where the ERK inhibitor SCH772984 (500 μg/kg) was injected via the femoral vein 15 min before brain trauma. At 2 h and 2 days after brain trauma, the permeability of blood-brain barrier was assessed by Evans blue method, the water content of the brain tissue was determined, and the phosphorylation level of ERK and the expression level of MMP-9 mRNA and protein were measured by RT-PCR and Western blotting.
RESULTS:
Compared with the sham-operated group, the rats with brain trauma exhibited significantly increased level of ERK phosphorylation at 2 h and significantly increased expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). Treatment with the ERK inhibitor significantly decreased the phosphorylation level of ERK after the injury ( < 0.01), suppressed over-expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). The permeability of blood-brain barrier increased significantly 2 h after brain trauma ( < 0.05) and increased further at 2 days ( < 0.01); the water content of the brain did not change significantly at 2 h ( > 0.05) but increased significantly 2 d after the injury ( < 0.01). Treatment with the ERK inhibitor significantly lowered the permeability of blood-brain barrier and brain water content after brain trauma ( < 0.01).
CONCLUSIONS
Blocking the activation of ERK pathway significantly reduced the over-expression of MMP-9 and alleviates the damage of blood-brain barrier and traumatic brain edema, suggesting that ERK signaling pathway plays an important role in traumatic brain edema by regulating the expression of MMP-9.
Animals
;
Brain Edema
;
drug therapy
;
etiology
;
Brain Injuries, Traumatic
;
complications
;
drug therapy
;
Gene Expression Regulation, Enzymologic
;
drug effects
;
Indazoles
;
pharmacology
;
therapeutic use
;
MAP Kinase Signaling System
;
drug effects
;
Matrix Metalloproteinase 9
;
genetics
;
Piperazines
;
pharmacology
;
therapeutic use
;
Protein Kinase Inhibitors
;
pharmacology
;
therapeutic use
;
Random Allocation
;
Rats
;
Rats, Sprague-Dawley
9.Blocking ERK signaling pathway lowers MMP-9 expression to alleviate brain edema after traumatic brain injury in rats.
Zhaohua TANG ; Wentao WANG ; Zili LIU ; Xiaochuan SUN ; Zhengbu LIAO ; Feilan CHEN ; Guangyuan JIANG ; Gang HUO
Journal of Southern Medical University 2020;40(7):1018-1022
OBJECTIVE:
To investigate the effects of blocking the activation of ERK pathway on the expression of matrix metalloproteinase-9 (MMP-9) and the formation of cerebral edema in SD rats after brain injury.
METHODS:
Ninety SD rats were randomly divided into 3 equal groups, including a sham-operated group, modified Feeney's traumatic brain injury model group, and ERK inhibition group where the ERK inhibitor SCH772984 (500 μg/kg) was injected via the femoral vein 15 min before brain trauma. At 2 h and 2 days after brain trauma, the permeability of blood-brain barrier was assessed by Evans blue method, the water content of the brain tissue was determined, and the phosphorylation level of ERK and the expression level of MMP-9 mRNA and protein were measured by RT-PCR and Western blotting.
RESULTS:
Compared with the sham-operated group, the rats with brain trauma exhibited significantly increased level of ERK phosphorylation at 2 h and significantly increased expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). Treatment with the ERK inhibitor significantly decreased the phosphorylation level of ERK after the injury ( < 0.01), suppressed over-expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). The permeability of blood-brain barrier increased significantly 2 h after brain trauma ( < 0.05) and increased further at 2 days ( < 0.01); the water content of the brain did not change significantly at 2 h ( > 0.05) but increased significantly 2 d after the injury ( < 0.01). Treatment with the ERK inhibitor significantly lowered the permeability of blood-brain barrier and brain water content after brain trauma ( < 0.01).
CONCLUSIONS
Blocking the activation of ERK pathway significantly reduced the over-expression of MMP-9 and alleviates the damage of blood-brain barrier and traumatic brain edema, suggesting that ERK signaling pathway plays an important role in traumatic brain edema by regulating the expression of MMP-9.
Animals
;
Blood-Brain Barrier
;
Brain Edema
;
Brain Injuries, Traumatic
;
MAP Kinase Signaling System
;
Matrix Metalloproteinase 9
;
Rats
;
Rats, Sprague-Dawley
10.Treatment strategy of the scar uterus patients in assisted reproduction
Xiaoli WU ; Hong YU ; Man LUO ; Ling YANG ; Huizhen TANG ; Zhaohua LIU ; Huilian CHEN ; Nannan LI
Journal of Chinese Physician 2020;22(9):1332-1336
Objective:To investigate the effect of scar uterus on assisted reproduction treatment strategy.Methods:From January 1, 2017 to December 31, 2017, 109 cases of scar uterus group and 63 cases of vaginal delivery history group who underwent in vitro fertilization-embryo transfer (IVF-ET) assisted pregnancy fresh embryo transfer in our hospital were retrospectively analyzed. Results:⑴ There was no significant difference in the total amount of gonadotropin (Gn) and the total days of GN in patients <35 between scar uterus group and the vaginal delivery history group ( P>0.05), but there were significant differences in the number of oocytes, mature oocytes, two pronucleus (2PN) and excellent embryos between the scar uterus group and the vaginal delivery history group ( P<0.05). When the age was ≥35 years old, there was no significant difference in the total number of GN, the total days of GN, the number of oocytes obtained, the number of mature oocytes, the number of 2PN and the number of excellent embryos between the two groups ( P>0.05). ⑵ There were no statistically significant differences in clinical pregnancy rate and embryo implantation rate between the two groups of patients < 35 years old, no matter single embryo transplantation or double embryos transplantation. When transplant two embryos, the clinical pregnancy rate and embryo implantation rate in the scar uterus group were slightly lower than those in the vaginal delivery history group (57.57% vs 71.05% and 39.39% vs 47.37%, respectively), but with no significant difference ( P>0.05). There were no statistically significant differences in the clinical pregnancy rate and embryo implantation rate between single embryo transplantation and double embryo transplantation in patients≥35 years old ( P>0.05). ⑶ There were no statistically differences in biochemical pregnancy rate, early abortion rate, preterm birth rate and average newborn weight between the scar uterus group and the vaginal delivery history group ( P>0.05). Conclusions:Cesarean section may affect the ovarian function. For patients with previous cesarean section, early evaluation of ovarian function is recommended. Single embryo transfer does not reduce the outcome in IVF-ET. It is recommended to perform single embryo transfer for patients with scar uterus to reduce the risk during pregnancy of twin pregnancy.


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