1.Process Optimization and Health Risk Assessment of Calcined Haematitum Based on QbD Concept
Yue YANG ; Jingwei ZHOU ; Jialiang ZOU ; Guorong MEI ; Yifan SHI ; Lei ZHONG ; Jiaojiao WANG ; Xuelian GAN ; Dewen ZENG ; Xin CHEN ; Lin CHEN ; Hongping CHEN ; Shilin CHEN ; Yuan HU ; Youping LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):187-196
ObjectiveTo investigate the processing technology of calcined Haematitum based on the concept of quality by design(QbD) and to assess its health risk. MethodsTaking whole iron content, Fe2+ dissolution content and looseness as critical quality attributes(CQAs), and calcination temperature, calcination time, spreading thickness and particle size as critical process parameters(CPPs) determined by the failure mode and effect analysis(FMEA), the processing technology of calcined Haematitum was optimized by orthogonal test combined with analytic hierarchy process-criteria importance through intercriteria correlation(AHP-CRITIC) hybrid weighting method. The contents of heavy metals and harmful elements were determined by inductively coupled plasma mass spectrometry, and the health risk assessment was carried out by daily exposure(EXP), target hazard quotient(THQ) and lifetime cancer risk(LCR), and the theoretical value of the maximum limit was deduced. ResultsThe optimal processing technology for calcined Haematitum was calcination at 650 ℃, calcination time of 1 h, particle size of 0.2-0.5 cm, spreading thickness of 1 cm, and vinegar quenching for 1 time[Haematitum-vinegar(10:3)]. The contents of 5 heavy metals and harmful elements in 13 batches of calcined Haematitum were all decreased with reductions of up to 5-fold. The cumulative THQ of 2 batches of samples was>1, while the cumulative THQ of all batches of Haematitum was>1. The LCR of As in 1 batches of Haematitum was 1×10-6-1×10-4, and the LCR of the rest was<1×10-6, and the LCRs of calcined Haematitum were all<1×10-6, indicating that the carcinogenic risk of calcined Haematitum was low, but special attention should still be paid to Haematitum medicinal materials. Preliminary theoretical values of the maximum limits of Cu, As, Cd, Pb and Hg were formulated as 1 014, 25, 17, 27, 7 mg·kg-1. ConclusionThe optimized processing technology of calcined Haematitum is stable and feasible, and the contents of heavy metals and harmful elements are reduced after processing. Preliminary theoretical values of the maximum limits of Cu, As, Cd, Pb and Hg are formulated to provide a scientific basis for the formulation of standards for the limits of harmful elements in Haematitum.
2.Process Optimization and Health Risk Assessment of Calcined Haematitum Based on QbD Concept
Yue YANG ; Jingwei ZHOU ; Jialiang ZOU ; Guorong MEI ; Yifan SHI ; Lei ZHONG ; Jiaojiao WANG ; Xuelian GAN ; Dewen ZENG ; Xin CHEN ; Lin CHEN ; Hongping CHEN ; Shilin CHEN ; Yuan HU ; Youping LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):187-196
ObjectiveTo investigate the processing technology of calcined Haematitum based on the concept of quality by design(QbD) and to assess its health risk. MethodsTaking whole iron content, Fe2+ dissolution content and looseness as critical quality attributes(CQAs), and calcination temperature, calcination time, spreading thickness and particle size as critical process parameters(CPPs) determined by the failure mode and effect analysis(FMEA), the processing technology of calcined Haematitum was optimized by orthogonal test combined with analytic hierarchy process-criteria importance through intercriteria correlation(AHP-CRITIC) hybrid weighting method. The contents of heavy metals and harmful elements were determined by inductively coupled plasma mass spectrometry, and the health risk assessment was carried out by daily exposure(EXP), target hazard quotient(THQ) and lifetime cancer risk(LCR), and the theoretical value of the maximum limit was deduced. ResultsThe optimal processing technology for calcined Haematitum was calcination at 650 ℃, calcination time of 1 h, particle size of 0.2-0.5 cm, spreading thickness of 1 cm, and vinegar quenching for 1 time[Haematitum-vinegar(10:3)]. The contents of 5 heavy metals and harmful elements in 13 batches of calcined Haematitum were all decreased with reductions of up to 5-fold. The cumulative THQ of 2 batches of samples was>1, while the cumulative THQ of all batches of Haematitum was>1. The LCR of As in 1 batches of Haematitum was 1×10-6-1×10-4, and the LCR of the rest was<1×10-6, and the LCRs of calcined Haematitum were all<1×10-6, indicating that the carcinogenic risk of calcined Haematitum was low, but special attention should still be paid to Haematitum medicinal materials. Preliminary theoretical values of the maximum limits of Cu, As, Cd, Pb and Hg were formulated as 1 014, 25, 17, 27, 7 mg·kg-1. ConclusionThe optimized processing technology of calcined Haematitum is stable and feasible, and the contents of heavy metals and harmful elements are reduced after processing. Preliminary theoretical values of the maximum limits of Cu, As, Cd, Pb and Hg are formulated to provide a scientific basis for the formulation of standards for the limits of harmful elements in Haematitum.
3.Immunomodulatory effect of short-chain fatty acids in hepatic encephalopathy and its potential diagnostic value
Weiyu CHEN ; Dewen MAO ; Han WANG ; Yang DU ; Wenqian FENG ; Lei FU ; Chun YAO
Journal of Clinical Hepatology 2025;41(5):954-962
Hepatic encephalopathy (HE) is a common complication of severe liver disease in the end stage, and it is urgently needed to improve the rate of effective treatment and clarify the pathogenesis of HE. The liver is a crucial hub for immune regulation, and disruption of immune homeostasis is a key factor in the pathological mechanisms of HE. As the main metabolites of intestinal flora, short-chain fatty acids (SCFAs) play a vital role in the biological processes of both innate and adaptive immunity and can regulate the proliferation and differentiation of immune cells maintain the homeostasis of intestinal microenvironment and the integrity of barrier function. Studies have shown that SCFAs participate in bidirectional and dynamic interactions with the liver-gut-brain axis through immunomodulatory pathways, thereby playing an important role in the diagnosis, treatment, and prognostic evaluation of HE. Starting from the immunoregulatory effect of SCFAs, this article summarizes and analyzes the crosstalk relationship between SCFAs and the liver-gut-brain axis and the significance of SCFAs in the diagnosis and treatment of HE, in order to provide new ideas for optimizing clinical prevention and treatment strategies.
4.The role of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in liver diseases
Yangling ZENG ; Yunyong WANG ; Haimei GUAN ; Tianwen WANG ; Baohua XIE ; Guobao LI ; Riyun ZHANG ; Tingshuai WANG ; Dewen MAO
Journal of Clinical Hepatology 2025;41(5):983-990
Cholesterol is an essential molecule for the biosynthesis of cell membranes and cell proliferation and differentiation, and the liver plays a central role in cholesterol metabolism and is responsible for the synthesis, uptake, secretion, and transport of cholesterol. The initial stages of cholesterol synthesis in the liver are particularly important, and abnormalities in such stages are closely associated with the progression of various liver diseases. Studies have shown that as a key rate-limiting enzyme in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) has well-defined regulatory properties and has been confirmed as an important target for the regulation of various liver diseases. This article reviews the process of cholesterol metabolism, the degradation and regulatory mechanisms of HMGCR, and the application of inhibitors, as well as the role of HMGCR in liver diseases, in order to provide new insights for scientific research and the clinical prevention and treatment of liver diseases.
5.Comprehensive Application of AHP-CRITIC Hybrid Weighting Method, Grey Correlation Analysis and BP-ANN in Optimization of Extraction Process of Qizhi Prescription
Qun LAN ; Yi CHENG ; Zian LI ; Bingyu WU ; Jinyu WANG ; Dewen LIU ; Yan TONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):176-186
ObjectiveBased on analytic hierarchy process(AHP)-criteria importance through intercriteria correlation(CRITIC) hybrid weighting method, grey relational analysis and backpropagation artificial neural network(BP-ANN), to optimize the water extraction process of Qizhi prescription, so as to provide an experimental basis for optimization of the preparation process of this prescription and the establishment of quality standards. MethodsL9(34) orthogonal test was employed, and the AHP-CRITIC hybrid weighting method was utilized to determine the weight coefficients of the quality fractions of various components, including astragaloside Ⅳ, polygalaxanthone Ⅲ, calycosin-7-O-β-D-glucoside, tenuifolin, and 3,6′-disinapoylsucrose, as well as the dry extract yield. The comprehensive score of each factor level combination in the orthogonal test were calculated as evaluation indicator to select the optimal extraction process parameters. The effects of extraction times, extraction time, and solvent dosage on the aqueous extraction process of the formula were investigated through intuitive analysis, variance analysis, and grey relational analysis. Meanwhile, a BP-ANN model was established to reverse-predict the optimal extraction process parameters of Qizhi prescription, and the optimized process parameters were validated. ResultsThe weight coefficients of the five index components(astragaloside Ⅳ, tenuifolin, calycosin-7-O-β-D-glucoside, polygalaxanthone Ⅲ, and 3,6′-disinapoylsucrose) and dry extract yield were 25.7%, 20.82%, 16.41%, 12.45%, 15.96% and 8.67%, respectively. The optimized extraction process parameters were extracted 3 times with 8, 6, 6 times the amount of water, each time for 1 h. The network prediction results of BP-ANN test samples were consistent with the orthogonal test results, and the mean square error(MSE) of the predicted and measured values of the network was <1%. The water extraction process of Qizhi prescription analyzed and predicted by relevant mathematical models was stable and feasible, which could effectively improve the extraction efficiency of the active ingredients of Astragali Radix and Polygalae Radix, and the average comprehensive score of the validation test was 90.85 with the relative standard deviation(RSD) of 1.55%. ConclusionThis study establishes a water extraction process for compound Qizhi granules, and the optimized extraction process can effectively improve the extraction efficiency of active ingredients, which provides useful references for the optimization of preparation process and the establishment of quality standards for other clinical experience formulas.
6.Construction and practice of the theory of “turbid toxin pathogenesis” and related prevention and treatment strategies for hepatic encephalopathy in traditional Chinese medicine/Zhuang medicine
Zhipeng WU ; Yuqin ZHANG ; Chun YAO ; Minggang WANG ; Na WANG ; Mengru PENG ; Ningfang MO ; Yaqing ZHENG ; Rongzhen ZHANG ; Dewen MAO
Journal of Clinical Hepatology 2025;41(2):370-374
Hepatic encephalopathy is a difficult and critical disease with rapid progression and limited treatment methods in the field of liver disease, and it is urgently needed to make breakthroughs in its pathogenesis. Selection of appropriate prevention and treatment strategies is of great importance in delaying disease progression and reducing the incidence and mortality rates. This article reviews the theory of “turbid toxin pathogenesis” and related prevention and treatment strategies for hepatic encephalopathy in traditional Chinese medicine/Zhuang medicine, proposes a new theory of “turbid toxin pathogenesis”, analyzes the scientific connotations of “turbid”, “toxin”, and the theory of “turbid toxin pathogenesis”, and constructs the “four-step” prevention and treatment strategies for hepatic encephalopathy, thereby establishing the new clinical prevention and treatment regimen for hepatic encephalopathy represented by “four prescriptions and two techniques” and clarifying the effect mechanism and biological basis of core prescriptions and techniques in the prevention and treatment of hepatic encephalopathy, in order to provide a reference for the prevention and treatment of hepatic encephalopathy.
7.Role of neutrophil extracellular traps in hepatocellular carcinoma
Xueru TIAN ; Weiyu CHEN ; Luyi YAN ; Yang HONG ; Han WANG ; Shouqin LIU ; Lei QING ; Guojuan MA ; Dewen MAO ; Chun YAO
Journal of Clinical Hepatology 2025;41(11):2410-2417
Hepatocellular carcinoma (HCC) is a malignant tumor with high incidence and mortality rates worldwide. Recent studies have shown that neutrophil extracellular traps (NETs) play an important role in the development, progression, and immune escape of HCC. NETs are released by neutrophils and mainly consist of DNA, histones, and antimicrobial molecules, and in addition to immune defense, they are also involved in the initiation, metastasis, and thrombosis of HCC. This article elaborates on the formation and regulatory mechanisms of NETs, explores their potential mechanisms in the initiation, metastasis, immune escape, and thrombosis of HCC, and discusses the prospect of NETs as a target for the diagnosis and treatment of HCC, in order to provide new ideas for the precise treatment of HCC in the future and promote the early diagnosis and effective treatment of HCC.
8.Research advances in traditional Chinese medicine regulation of programmed cell death in intervening against hepatic fibrosis
Liangjiang HUANG ; Dewen MAO ; Rongzhen ZHANG ; Guochu HUANG ; Han WANG ; Weibin QIN ; Chun YAO
Journal of Clinical Hepatology 2024;40(1):161-168
Hepatic fibrosis (HF) is a pathological process of abnormal repair of liver tissue structure caused by chronic liver injury, and its pathogenesis has not been fully clarified. Related studies have shown that programmed cell death may be associated with the onset of HF, and traditional Chinese medicine (TCM) has a significant effect in regulating programmed cell death to intervene against HF. This article reviews the main mechanism of the influence of programmed cell death on HF and discusses the possible mechanism of TCM regulation of programmed cell death in improving HF, which provides new ideas for TCM prevention and treatment of HF.
9.Role of neuroimmune communication via the gut-brain axis in the pathogenesis of hepatic encephalopathy
Yong LIN ; Jiongfen LI ; Feiyan LI ; Yuanqin DU ; Meiyan LIU ; Minggang WANG ; Fuli LONG ; Na WANG ; Dewen MAO
Journal of Clinical Hepatology 2024;40(12):2518-2523
Hepatic encephalopathy (HE) is a common severe liver disease syndrome in clinical practice and is one of the critical and severe diseases in internal medicine, and more than half of liver failure patients diagnosed with overt HE have a survival time of less than 1 year. A comprehensive analysis of the complex pathogenesis of HE and the development of diagnosis and treatment regimens based on evidence-based medicine are of great importance for alleviating high medical resource consumption, high medical expenses, and high incidence and mortality rates in clinical practice. The latest studies have shown that the intestinal tract and the central nervous system can perform bidirectional continuous interaction and signal transmission and regulate the function of inflammation signals, molecules, cells, and organs, which is known as neuroimmune communication and is highly consistent with the main pathological features of HE. With a focus on the mechanism of neuroimmune communication in HE, this article reviews the association between inflammation signal transduction via the gut-brain axis and neurotransmitter regulation and its role in neuroimmune communication in HE, which provides new ideas for the clinical diagnosis and treatment of HE and the research and development of related drugs.
10.Mediating effect of negative emotions on visual impairment and resilience among middle-aged and elderly populations
WU Zhengyu ; WANG Dewen ; LIU Zhengkui
Journal of Preventive Medicine 2024;36(1):5-8
Objective :
To investigate the mediating effect of negative emotions on visual impairment and resilience among middle-aged and elderly populations, so as to provide insights into improving psychological health among middle-aged and elderly populations.
Methods:
Demographic information, visual impairment, negative emotions and resilience in the residents at ages of 45 years and older were collected through the database of the Yushu Physical and Mental Health Survey carried out by Institute of Psychology of Chinese Academy of Sciences. Structural equation model was used to analyze the effects of visual impairment and resilience and the mediating role of negative emotions.
Results:
Totally 2 997 middle-aged and elderly populations were enrolled, with the median age of 50.00 (interquartile range, 47.00) years. There were 1 320 males (44.04%) and 1 677 females (55.96%), 1 627 illiterate persons (54.29%), and 2 780 married persons (92.76%). The scores of visual impairment, negative emotions and resilience were (6.79±2.59), (6.35±3.05) and (33.38±10.41) points, respectively. The results of structural equation model analysis showed that after adjusting for age, gender, educational level and marital status, visual impairment had a direct negative positive effect on resilience, with a direct effect value of -0.157 (95%CI: -0.177 to -0.137), and visual impairment could also negatively affect residence through negative emotions, with a mediating effect value of -0.112 (95%CI: -0.126 to -0.104), and the mediating effect contributed 41.64% to the total effect.
Conclusion
visual impairment could reduce residence directly or indirectly through the mediating effect of negative emotions among middle-aged and elderly populations.


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