Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.

Background: The previous research has confirmed the existence of idiosyncratic drug-induced liver injury (IDILI) caused by Polygonum multiflorum (PM-IDILI), and demonstrated that PM-IDILI is an immune-mediated injury, with HLA-B*35:01 identified as a genetic susceptibility marker. Additionally, emodin-8-O-β-D-glucoside (EG) and 2, 3, 5, 4′-tetrahyd roxystilbene-2-O-β-D-glucoside have been proposed as potential contributory ingredients in the pathogenesis of PM-IDILI. However, the precise mechanisms through which these susceptible factors contribute to the development of PM-IDILI remain unclear. Objectives: This study aims to explore the molecular characteristics of HLA-B*35:01 that contribute to PM-DILI and to propose a mechanistic hypothesis based on our previous research on PM-induced protein adducts. Methods: Key differences between HLA-B*35:01 and general Chinese HLA-B alleles were identified by comparing protein sequences, peptide binding motifs, and protein structures. Molecular docking was employed to assess whether PM-induced haptenated peptides can be presented by HLA-B*35:01 and other related alleles. Additionally, a simplified dipeptide model was used to evaluate the binding affinity of HLA-B*35:01 to EG-haptenated peptides. Results: Our findings revealed significant differences in the residues of the B and F peptide binding pockets of HLA-B*35:01 compared to general Chinese HLA-B alleles. Further analysis suggested that the F pocket of HLA-B*35:01 was capable of binding EG-cysteine adducts and might be a key feature in the PM-IDILI pathogenesis. Peptide docking using DINC and molecular dynamics simulations indicated that HLA-B*35:01 could form stable complexes with EG-haptenated peptides. Molecular dynamics simulations also highlighted the critical roles of both the B and F pockets in peptide binding. Specifically, the F pocket binds the EG-modified residue in haptenated peptides, while the B pocket, despite lacking shared features among PM-IDILI patients, may indirectly influence the incidence of PM-IDILI by filtering haptenated peptides. The binding affinity of HLA-B*35:01 to EG-modified cysteine residues was experimentally validated through a dipeptide-based assay, confirming that HLA-B*35:01 could bind EG-haptenated peptides. Conclusions: This study identified the unique B and F binding pockets of HLA-B*35:01 as key factors in PM-IDILI pathogenesis and demonstrated that HLA-B*35:01 could bind EG-haptenated peptides. These findings suggest that PM-IDILI may be a hapten-based drug hypersensitivity reaction driven by EG, providing a theoretical framework for further research aimed at elucidating the molecular mechanisms underlying PM-IDILI.

Background: The previous research has confirmed the existence of idiosyncratic drug-induced liver injury (IDILI) caused by Polygonum multiflorum (PM-IDILI), and demonstrated that PM-IDILI is an immune-mediated injury, with HLA-B*35:01 identified as a genetic susceptibility marker. Additionally, emodin-8-O-β-D-glucoside (EG) and 2, 3, 5, 4′-tetrahyd roxystilbene-2-O-β-D-glucoside have been proposed as potential contributory ingredients in the pathogenesis of PM-IDILI. However, the precise mechanisms through which these susceptible factors contribute to the development of PM-IDILI remain unclear. Objectives: This study aims to explore the molecular characteristics of HLA-B*35:01 that contribute to PM-DILI and to propose a mechanistic hypothesis based on our previous research on PM-induced protein adducts. Methods: Key differences between HLA-B*35:01 and general Chinese HLA-B alleles were identified by comparing protein sequences, peptide binding motifs, and protein structures. Molecular docking was employed to assess whether PM-induced haptenated peptides can be presented by HLA-B*35:01 and other related alleles. Additionally, a simplified dipeptide model was used to evaluate the binding affinity of HLA-B*35:01 to EG-haptenated peptides. Results: Our findings revealed significant differences in the residues of the B and F peptide binding pockets of HLA-B*35:01 compared to general Chinese HLA-B alleles. Further analysis suggested that the F pocket of HLA-B*35:01 was capable of binding EG-cysteine adducts and might be a key feature in the PM-IDILI pathogenesis. Peptide docking using DINC and molecular dynamics simulations indicated that HLA-B*35:01 could form stable complexes with EG-haptenated peptides. Molecular dynamics simulations also highlighted the critical roles of both the B and F pockets in peptide binding. Specifically, the F pocket binds the EG-modified residue in haptenated peptides, while the B pocket, despite lacking shared features among PM-IDILI patients, may indirectly influence the incidence of PM-IDILI by filtering haptenated peptides. The binding affinity of HLA-B*35:01 to EG-modified cysteine residues was experimentally validated through a dipeptide-based assay, confirming that HLA-B*35:01 could bind EG-haptenated peptides. Conclusions: This study identified the unique B and F binding pockets of HLA-B*35:01 as key factors in PM-IDILI pathogenesis and demonstrated that HLA-B*35:01 could bind EG-haptenated peptides. These findings suggest that PM-IDILI may be a hapten-based drug hypersensitivity reaction driven by EG, providing a theoretical framework for further research aimed at elucidating the molecular mechanisms underlying PM-IDILI.

Background: The previous research has confirmed the existence of idiosyncratic drug-induced liver injury (IDILI) caused by Polygonum multiflorum (PM-IDILI), and demonstrated that PM-IDILI is an immune-mediated injury, with HLA-B*35:01 identified as a genetic susceptibility marker. Additionally, emodin-8-O-β-D-glucoside (EG) and 2, 3, 5, 4′-tetrahyd roxystilbene-2-O-β-D-glucoside have been proposed as potential contributory ingredients in the pathogenesis of PM-IDILI. However, the precise mechanisms through which these susceptible factors contribute to the development of PM-IDILI remain unclear. Objectives: This study aims to explore the molecular characteristics of HLA-B*35:01 that contribute to PM-DILI and to propose a mechanistic hypothesis based on our previous research on PM-induced protein adducts. Methods: Key differences between HLA-B*35:01 and general Chinese HLA-B alleles were identified by comparing protein sequences, peptide binding motifs, and protein structures. Molecular docking was employed to assess whether PM-induced haptenated peptides can be presented by HLA-B*35:01 and other related alleles. Additionally, a simplified dipeptide model was used to evaluate the binding affinity of HLA-B*35:01 to EG-haptenated peptides. Results: Our findings revealed significant differences in the residues of the B and F peptide binding pockets of HLA-B*35:01 compared to general Chinese HLA-B alleles. Further analysis suggested that the F pocket of HLA-B*35:01 was capable of binding EG-cysteine adducts and might be a key feature in the PM-IDILI pathogenesis. Peptide docking using DINC and molecular dynamics simulations indicated that HLA-B*35:01 could form stable complexes with EG-haptenated peptides. Molecular dynamics simulations also highlighted the critical roles of both the B and F pockets in peptide binding. Specifically, the F pocket binds the EG-modified residue in haptenated peptides, while the B pocket, despite lacking shared features among PM-IDILI patients, may indirectly influence the incidence of PM-IDILI by filtering haptenated peptides. The binding affinity of HLA-B*35:01 to EG-modified cysteine residues was experimentally validated through a dipeptide-based assay, confirming that HLA-B*35:01 could bind EG-haptenated peptides. Conclusions: This study identified the unique B and F binding pockets of HLA-B*35:01 as key factors in PM-IDILI pathogenesis and demonstrated that HLA-B*35:01 could bind EG-haptenated peptides. These findings suggest that PM-IDILI may be a hapten-based drug hypersensitivity reaction driven by EG, providing a theoretical framework for further research aimed at elucidating the molecular mechanisms underlying PM-IDILI.

ObjectiveThis paper aims to analyze the clinical characteristics and medication rationality of liver injury related to Epimedii Folium preparation （EP） and explore the possible risk factors of liver injury， so as to provide a reference for the safe clinical application of Epimedii Folium （EF）. MethodA retrospective analysis was conducted on liver injury cases related to EP from 2012 to 2016. ResultThe number of reported liver injury cases and the proportion of severe cases related to the use of EP show an increasing trend， indicating the objective existence of liver injury caused by EP. There are more cases of liver injury related to EP in women than in men， with an onset age range of 15-91 years old and a median onset age of 60 years old （median onset ages for men and women are 59 and 60 years old， respectively）. The time span from taking EP alone to the occurrence of liver injury is 1-386 days， with a median of 38 days. The time span from taking both EP and Western medicine to the occurrence of liver injury is 1-794 days， with a median of 34 days. EF-related liver injury preparations are mostly composed of traditional Chinese medicines that promote immunity and tonify the liver and kidney， indicating that immune stress in the body may be the mechanism of liver injury caused by the use of EP alone or in combination. There is no increasing trend of toxicity with time or dose in the liver injury caused by EP. By further exploring its risk factors， it is found that patients have unreasonable medication methods such as excessive dosage， repeated use， and multi-drug combination， which may also be one of the important risk factors for EF-related liver injury. ConclusionEP has a certain risk of liver injury and should be emphasized in clinical diagnosis and treatment. Immune stress may be the mechanism of liver injury caused by EP， and in clinical use， it is necessary to be vigilant about the risk of liver injury caused by unreasonable use and combined use with Western medicine.

Pharmaceutical analysis is a discipline based on chemical, physical, biological, and information technologies. At present, biotechnological analysis is a short branch in pharmaceutical analysis; however, bioanalysis is the basis and an important part of medicine. Biotechnological approaches can provide information on biological activity and even clinical efficacy and safety, which are important characteristics of drug quality. Because of their advantages in reflecting the overall biological effects or functions of drugs and providing visual and intuitive results, some biotechnological analysis methods have been gradually applied to pharmaceutical analysis from raw material to manufacturing and final product analysis, including DNA super-barcoding, DNA-based rapid detection, multiplex ligation-dependent probe amplification, hyperspectral imaging combined with artificial intelligence, 3D biologically printed organoids, omics-based artificial intelligence, microfluidic chips, organ-on-a-chip, signal transduction pathway-related reporter gene assays, and the zebrafish thrombosis model. The applications of these emerging biotechniques in pharmaceutical analysis have been discussed in this review.

Objective:To document the blood indexes of middle-aged and elderly intracerebral hemorrhage (ICH) patients complicated with deep vein thrombosis (DVT).Methods:A retrospective analysis was conducted of 77 hospitalized ICH patients using venous color Doppler ultrasonography within 3 days of admission. According to the results, they were divided into a DVT group (18 cases) and a non-DVT group (59 cases). The blood routine, biochemistry, coagulation, and D-dimer examinations were conducted on the 2nd day after admission. T-tests and rank sum tests tested the significance of any differences between the groups in average white blood cell counts, neutrophil percentages, platelets, albumin, globulin, fasting blood glucose, urea nitrogen, creatinine, uric acid, electrolytes, fibrinogen or D-dimer.Results:The average levels of albumin, uric acid and calcium in the DVT group were significantly lower than in the non-DVT group. The average levels of fasting blood glucose and D-dimer were significantly higher.Conclusions:Decreased serum uric acid, calcium and albumin levels, together with increased fasting blood glucose and D-dimer are related to the occurrence of DVT in ICH patients. To reduce the risk of DVT it is important to maintain normal levels of serum uric acid, calcium and albumin and to limit D-dimer and fasting blood glucose.

To screen strains with antibacterial and antitumor activity, pregnenolone was used as the sole carbon source for screening bacteria from soil. Based on bacteriostatic activity assay, Pseudomonas aeruginosa HBD-12 was found to be effectively inhibiting the growth of Escherichia coli, Bacillus thuringiensis, Penicillium digitatum and Penicillium italicum, and its fermentation broth was separated and purified using column chromatography. Then, structure of the obtained monomeric compounds was analyzed by spectrum analysis, and their antitumor activity was measured using HTRF kinase detection kit. The isolated monomeric compounds 1-hydroxy-9,10-phenanthroline and 3-hydroxy-9,10-dihydrophenanthroline had significant antitumor activity. At 20 μg/mL, 1-hydroxy-9,10-phenanthroline and 3-hydroxy-9,10-dihydrophenanthroline inhibited 78.39±2.29% and 60.34±8.35% Aurora kinase A, respectively. Therefore, the secondary metabolites of Pseudomonas aeruginosa HBD-12 have the potential to develop antibacterial and antitumor drugs.
Anti-Bacterial Agents/pharmacology* ; Microbial Sensitivity Tests ; Penicillium ; Pseudomonas aeruginosa

Objective To study the participating farmers'interest demands for NRCMs in order to provide basis for the payment system reform based on the demand side perspective. Methods A cross-sectional study was conducted from September 2016 to February 2017. Multi-stage stratified random sampling was conducted in six counties of three provinces in the eastern, middle and western regions of China. Mathematical statistics analysis was conducted to clarify the interest demands and influencing factors of the participating farmers. Results The interests claims of the 1 452 participating farmers were to improve service quality, to reduce the economic burden of disease, and to standardize the management. The medians found were 4.00, 4.00 and 3.63 respectively. Relative to the flat rate, the DRGs raised higher requirements for standardized medical behaviors offered by the medical workers. Furthermore, it called for effective medical quality supervision, rigorous control of medical costs and highly scientific and standardized management. The differences were statistically significant ( P ＜0.05 ). Conclusions The diversity of participating farmers'interest demands deserves due attention, the payment methods combination should fit local needs, the interests demands expression channel of the participants should be expanded, and the demand side deserves a due role in supervision of the funds.

Objective To further improve the comprehensive evaluation program of patient satisfaction in view of the defective item screening and weight design short of considerations for patients'psychological expectation and rational judgment, based on the theory of bounded rationality. Methods A satisfaction measurement scale was compiled and used to survey 847 inpatients in July-August 2017. The internal consistency test, correlation and factor analysis were used to evaluate the reliability and validity of the scale. The combination weight PWi was calculated based on patients' importance of the five satisfaction dimensions and the scoring of certainty degree of their responses. The combination weight EWi was calculated based on the five-dimension importance and operability scoring of expert consultation. The indicator combination weight OWi was determined using the integrated factors scoring, TOPSIS, weight rank-sun ratio, gray correlation method, and synthetic index method were used in a general assessment of patient satisfaction of a hospital in question. Results The Cronbach α coefficient of the patient satisfaction rating scale was 0.939, and the half-reliability coefficient was 0.951. The cumulative contribution rate of the five common factors variance extracted from the factor analysis was 71. 4%. The rational weights of five dimensions of service environment, service efficiency, service attitude, service technology, and service costs were 0.220, 0.214, 0.217, 0.179, and 0.171 respectively, while the comprehensive weights of the five dimensions were 0.115, 0.233, 0.196, 0.264, and 0.192 respectively. The comprehensive evaluation results of the two correlation coefficients were greater than 0.95. Conclusions The patient satisfaction measurement scale developed based on the theory of bounded rationality can expand the index connotation and items of core elements such as service technology and cost. The design of index weights fits with the concern of medical service factors and the degree of rational judgment in the patient's medical treatment process. The evaluation results are basically consistent with the actual situation and can be used as a reference tool for the scientific rational evaluation of patient satisfaction.