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.

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.

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.

Objective:To evaluate the effects of low-frequency ultrasound on antibiotic susceptibility and biofilm formation of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli).Methods:After MRSA and E. coli were treated with low-frequency ultrasound with different parameters, they were divided into a group with different ultrasound durations and a group with different ultrasound powers. With the power parameter set at 100%, the former was divided into 5 subgroups: control, 1.0 min, 2.5 min, 5.0 min, and 10.0 min subgroups. The bacteria were sonicated for 0, 1.0, 2.5, 5.0, 10.0 min, respectively. The group with different ultrasound powers was also divided into 5 subgroups: control, 25% power, 50% power, 75% power, and 100% power subgroups. The bacteria were treated with ultrasonic powers of 0, 25%, 50%, 75%, and 100% for 5.0 min. The MRSA and E. coli corresponded to antibiotic susceptibility testing using vancomycin and meropenem. The number of bacteria surviving was assessed by colony counts. Confocal microscopy was used to observe the changes in biofilms co-cultured with 1/2 minimum inhibitory concentration (MIC) antibiotics after sonication.Results:The E. coli enhanced its susceptibility to meropenem after 5.0 min of high-power sonication while the susceptibility of MRSA to vancomycin was unaffected. The number of E. coli decreased significantly with increasing ultrasound time and power: the numbers of E. coli in the 1.0 min, 2.5 min, 5.0 min, and 10.0 min subgroups [(51.00±18.73), (30.00±9.17), (5.33±4.04), and (0.23±0.03)×10 4 CFU/mL] were significantly smaller than that in the control subgroup [(120.00±7.81)×10 4 CFU/mL], and the numbers of E. coli in the 25%, 50%, 75%, and 100% subgroups [(25.00±3.00), (8.00±2.65), (5.00±2.00), and (5.33±4.04)×10 4 CFU/mL] were significantly smaller than that in the control subgroup [(120.00±7.81)×10 4 CFU/mL] ( P<0.05). However, the number of MRSA was not significantly affected. After treatment with ultrasound combined with 1/2 MIC meropenem, the ratio of live/dead biofilm areas of E. coli decreased significantly with increasing ultrasound time and power: the proportions of E. coli in the 1.0 min, 2.5 min, 5.0 min and 10.0 min subgroups (66.10%±1.78%, 50.84%±7.99%, 60.98%±2.23%, and 29.20%±16.49%) were significantly smaller than those in the control subgroup (93.73%±0.44%), and the proportions of E. coli in the 25%, 50%, 75%, and 100% subgroups (75.23%±2.21%, 65.10%±1.25%, 57.34%±11.21%, and 60.98%±2.23%) were significantly smaller than that in the control subgroup (93.73%±0.44%) ( P<0.05). However, the MRSA live/dead biofilm area ratio was not significantly affected by the treatment with ultrasound combined with 1/2 MIC vancomycin. Conclusions:Low frequency ultrasound can effectively inhibit the growth of E. coli and significantly enhance its sensitivity to antibiotics, and its combination with antibiotics can inhibit the formation of bacterial biofilm. However, low frequency ultrasound or its combination with antibiotics has no significant effect on MRSA.

Objective:To study the mechanistic role of Jiedu Huayu granule in improving intestinal mucosal barrier functional damage and protecting against liver failure in mice induced by D-galactosamine combined with lipopolysaccharide.Methods:Fifty mice were randomly divided into a normal group, a model group, a low-dose Jiedu Huayu granule group (4.16 g·kg -1·d -1), a medium-dose Jiedu Huayu granule group (8.32 g·kg -1·d -1), and a high-dose Jiedu Huayu granule group (16.64 g·kg -1·d -1). D-galactosamine combined with lipopolysaccharide was administered once to establish an acute liver failure mouse model, followed by corresponding drug intervention. Retro-orbital blood samples were collected to measure serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels six hours after modeling in mice. The endotoxin content was detected using the limulus reagent method. The content of serum interleukin-1β, tumor necrosis factor-α, and interferon-γ levels were detected using enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was used to observe liver and intestinal pathological tissues.Western blot and RT-PCR were used to determine the protein and mRNA expression of Occludin, Zo-1, Tricellulin, and CLDN3 in intestinal tissues. Multiple quantitative data were analyzed using one-way ANOVA, following a normal distribution. LSD-t test was used for statistical analysis between inter-groups. Results:The medium-and high-dose Jiedu Huayu granules had reduced and improved liver function impairment, liver pathological tissue damage, intestinal barrier damage, serum endotoxin and inflammatory factors ( P<0.05), and increased intestinal expression of occludin, Zo-1, Tricellulin, and CLDN3 ( P<0.05) in mice group with acute liver failure. Conclusion:Jiedu Huayu granules can reduce liver inflammatory damage, gut-derived endotoxemia, bacterial endotoxins entering the liver, and protect intestinal barrier function, thereby remissioning liver inflammation and antagonizing liver failure in mice with acute liver failure.

Hepatic encephalopathy is a neuropsychiatric syndrome secondary to severe liver disease.Recent studies have shown that the development of hepatic encephalopathy is closely associated with bile acid/short-chain fatty acid metabolic disorder.As the core theory of traditional Chinese medicine,the theory of Yin and Yang provides a unique perspective for analyzing the association between bile acids/short-chain fatty acids and hepatic encephalopathy.Bile acids function like Yang,governing the free flow of Qi and assisting in metabolic processes,while short-chain fatty acids belong to Yin,maintaining internal stability and conservation,preserving the intestinal barrier,and combating inflammation and toxins.Bile acids and short-chain fatty acids constrain each other and are interdependent to regulate the dynamic equilibrium of the gut-liver-brain axis.On this basis,by regulating the metabolic imbalance of bile acids and short-chain fatty acids,it is expected to restore the dynamic balance of Yin and Yang in patients with hepatic encephalopathy under the synergistic intervention of traditional Chinese medicine and Western medicine.

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.

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.

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.

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.