OBJECTIVE To discuss technical considerations for the design of efficacy evaluation indicators for drugs used in the treatment of kidney disease. METHODS Based on practical experience in disease characteristics, drug development, and evaluation, technical recommendations were proposed for designing efficacy evaluation indicators for kidney disease treatment drugs. RESULTS and CONCLUSION Renal failure and cardiovascular death are considered as the primary clinical outcomes for evaluating the efficacy of drugs used in kidney disease treatment. Based of the urgent clinical need and slow progression of kidney disease, exploring the selection and application of intermediate/surrogate indicators holds significant clinical value. Some evidence suggests that improvement in estimated glomerular filtration rate (eGFR) slope can partially predict the clinical benefits of treatment on chronic kidney disease (CKD) progression, making it a potential alternative indicator for early or slowly progressing CKD patients in drug trials. The correlation between elevated urinary protein levels and duration with renal function loss in lupus nephritis, membranous nephropathy, and IgA nephropathy indicates their potential for predicting renal outcomes; however, further research evidence is still required. In conclusion, when selecting indicators to evaluate efficacy, scientific design should be based on trial objectives, target population characteristics, drug mechanisms of action, and effect intensity while carefully considering surrogate indicators.

OBJECTIVE To investigate the influencing factors and test methods of viable bacterial count in probiotic products of nature Bifidobacterium, and provide reference and suggestions for improving the quality control of such products. METHODS The effects of storage temperature and viable count determination method on viable count were studied, and the pretreatment methods and diluent composition were optimized, and the drug resistance genes and virulence genes of 11 strains contained in four products were analyzed by whole genome sequencing and functional genomics analysis. RESULTS The results showed that temperature had a great influence on the results of viable bacteria count of Bifidobacteria products, and the optimized method of live bacteria count could effectively improve the count results. Several strains of live bacteria products contained drug resistance genes and virulence genes. CONCLUSION It is suggested that we should pay attention to the influence of temperature on products in production storage and circulation. The count method of live bacteria can consider the characteristics of strains and production technology, and optimize the influencing factors such as pre-treatment and diluent. And there is a need for systematic safety assessment of all strains involved in commercially live bacteria product.

OBJECTIVE To prepare t he immobilized α-L-rhamnosidase on SBA 15 mesoporous silica to promote the efficient conversion of epimedin C to icariin. METHODS SBA-15 was modified through amination and aldehydeylation, and the α-L-rhamnosidase was covalently coupled onto SBA-15. The immobilization conditions were optimized using the enzyme loading capacity and relative enzyme activity as evaluation index. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), N₂ adsorption-desorption analysis, scanning electron microscopy (SEM) and transmission electron microscope (TEM) were used to characterize the physicochemical properties of immobilized α-L-rhamnosidase. Using epimedin C as substrate and free α-L-rhamnosidase as control, the optimal enzymatic hydrolysis conditions, enzymatic kinetic parameters and recyclability of the immobilized α-L-rhamnosidase were investigated. RESULTS The optimal pH was 3.5, the optimal temperature was 35 ℃, the optimal immobilization time was 4 h and the optimal α-L-rhamnosidase concentration was 8 mg·mL^-1. The immobilized α-L-rhamnosidase showed a well-retained activity of 198.6 μmol·h^-1·g^-1 as well as a high enzyme loading capacity of 256.9 mg·g^-1 support. The optimum hydrolysis conditions were as follows: pH 4.5, conversion temperature 50 ℃, substrate concentration 0.5 mg·mL^-1, and transformation time 12 h. The V_max and K_m of the immobilized α-L-rhamnosidase was 0.505 μg·min^-1 and 0.787 mmol·L^-1, respectively. After four cycles of reuse, the residual relative enzyme activity of the immobilized α-L-rhamnosidase was more than 65%, which showed good stability. CONCLUSION The immobilized α-L-rhamnosidase has a high enzyme loading capacity, strong enzyme activity and good reusability, which can be used for efficient conversion of epimedin C to icariin.

OBJECTIVE To investigate the effects of age, gender, body mass index (BMI), type of epilepsy, dosage and combined medication on the steady-state serum concentration of perampanel in children with epilepsy. METHODS A total of 95 serum samples from 4 to 14 years old children with epilepsy who were admitted to our hospital from 2019 to 2023 and took perampanel regularly were collected. The serum concentration was determined by high performance liquid chromatography. The influence of factors such as gender, BMI, dosage and combined medication on the concentration were analyzed. RESULTS The children aged 4.25-14 (7.25±3.99) years. The serum concentration of perampanel was 0.13-0.99(0.47±0.36)μg·mL^-1. There were no significant differences in the serum concentration and ratio of concentration dose (CDR) of perampanel among different age groups and gender groups (P>0.05). The CDRs of patients of 18.5≤BMI<24.0 group were significantly higher than those of BMI<18.5 group (t=-1.207, P<0.05). The combination of drug had no significant effects on the dosage, blood concentration and CDR of perampanel (P>0.05). The correlation between perampanel concentration and dose was poor (r=0.113). CONCLUSION In the course of using perampanel for the treatment of epilepsy in children, it is necessary to conduct therapeutic drug monitoring, so that the concentration can be controlled within the therapeutic range to ensure clinical efficacy and reduce the incidence of adverse reactions.

OBJECTIVE To establish a method for identifying the authenticity of Artemisiae Argyi Folium suitable for use in drug regulatory work. METHODS The near-infrared spectra of samples of Artemisiae Argyi Folium and counterfeit were determined, and the experimental data was processed using feature engineering related techniques, such as feature screening and feature derivation. The training set and test set were divided randomly, and the logistic regression model, a classic model in the field of machine learning, was trained in 2-class mode and evaluated with the training set data and the test set data used, respectively. RESULTS The discrimination accuracy of the samples in the test set was 97%, and the other evaluation indicators were also above 92% with the logistic regression model. In addition, the results of discrimination between genuine and counterfeit mixed samples were also relatively accurate. Compared with traditional chemometrics methods, the machine learning used in the study had higher discrimination accuracy. CONCLUSION The logistic regression model established in this study can achieve the authenticity identification of Artemisiae Argyi Folium, providing technical support for actual drug regulatory work.

OBJECTIVE To investigate the attribution of berberine hydrochloride in the biological pharmaceutics classification system (BCS) and to determine its taxonomic properties. METHODS The solubility of berberine hydrochloride was investigated in pH 1.0-8.0 medium; its absorption parameters related to the rat duodenum, jejunum, ileum and colon were derived from in-situ intestinal perfusion model in vivo to determine its permeability. RESULTS The solubility in different pH dissolution media with the value of drug metering number (D₀) and combined with the pharmacopoeia regulations found that berberine hydrochloride belonged to the low solubility drugs. From the results of permeability experiments, it was found that the permeability coefficient P_eff(rat) of berberine hydrochloride in each intestinal segments was exceeded than 5.0×10^-5 cm·s^-1 in rats, and the conversion into human absorption F_a(human) was exceeded than 85%, therefore, it was determined to be the high permeability drug. CONCLUSION The combination of solubility and permeability test results proves that berberine hydrochloride is a low solubility and high permeability drug, which belongs to BCS class Ⅱ.

Non-alcoholic steatohepatitis (NASH), a severe subtype of non-alcoholic fatty liver disease (NAFLD), is emerging as a major health threat worldwide. However, due to its complex pathogenesis, there are currently no marketed drugs for NASH. The disease is not only involved in fat accumulation, but also accompanied by inflammation and fibrosis processes, in which inflammation plays an important role in the progression of NASH, long-term inflammatory response, can promote liver fibrosis and lipid homeostasis imbalance. Therefore, inhibiting inflammation is of great significance in improving NASH. This review systematically reviews the mechanism of action of inflammatory signaling pathways such as mitogen-activated protein kinase(MAPK), nuclear factor-κB(NF-κB), inactive rhomboid-like protein 2(iRhom2) and inflammasome in the development of NASH, and the current research status of related drugs such as Selonsertib, SHR0302 and fisetin, and further discusses the research progress of new targets for the treatment of NASH. It aims to provide new ideas for the research and development of drugs for NASH.

Red yeast rice is a kind of traditional Chinese medicine(TCM) commonly used in China and all over the world in medicine, food additives, fermented food and other fields, but the research in this TCM is far from enough. Recently, the safety of red yeast rice health care product has aroused great concern around the world. This article reviews studies on the applied history, fermentation processing technology, material basis and quality control status of red yeast rice, aiming to clarify the factors that may lead to the risk of quality and safety of red yeast rice, and provide references for the safety quality control and risk prevention and control of red yeast and its products in China.

OBJECTIVE To establish a high performance liquid chromatography (HPLC) method for the detection of related substances in somatostatin for injection. METHODS The determination was performed on a C₁₈ column with mobile phases consisting of potassium dihydrogen phosphate solution and acetonitrile by gradient elution. The detection wavelength was set at 215 nm and the column temperature was maintained at 50 ℃. RESULTS The established method can effectively separate the main components and seven major degradation impurities. The peak area of somatostatin and 7 kinds of impurities had good linear relationships with the concentration (r≥0.999 1, n=8). Relative standard deviation (RSD) of precision, stability and repeatability tests of 7 kinds of impurities were all lower than 3.6%. The average recoveries of 7 kinds of impurities ranged from 100.0% to 104.4% (n=9). The impurity content determined by the established method is higher than that determined by the European Pharmacopoeia(EP) and Chinese Pharmacopoeia(Ch.P). CONCLUSION The method is simple, accurate and stable. It can control the impurities in somatostatin for injection and provide a basis for improving the standard of this drug.

OBJECTIVE To establish a method based on gas chromatography-mass spectrometry (GC-MS) for simultaneous determination of a variety of soluble sugars in Ophiopohon japonicus tuberous roots and fibrous roots and to analyze the differences in the soluble sugars by multivariate statistical analysis. METHODS The optimized two-step derivatization method of methoxylation-trimethylsilylation combined with GC-MS was used to determine the soluble sugar components in 18 batches of Ophiopohon japonicus tuberous roots and fibrous roots. And the differences in the components were analyzed by multivariate statistical analysis, and the sweetness values of the tuberous roots and fibrous roots samples were converted according to the contents. RESULTS Eighteen kinds of soluble sugars were identified and 14 kinds of them were quantitatively analyzed in the tuberous roots and fibrous roots of Ophiopohon japonicus. It was found that the ingredients of the soluble sugar components in the tuberous roots and fibrous roots of Ophiopohon japonicus were basically the same, and the average of the total contents of the 14 kinds of soluble sugar components were also basically the same (88.76 mg·g^-1 in tuberous roots vs. 85.66 mg·g^-1 in fibrous roots). However, there were some differences in the contents of the components, and the contents of D-(-)-fructose and in the fibrous roots were significantly higher than those in the tuberous roots, while the contents of D-(+)-sucrose in the tuberous roots were significantly higher than those in the fibrous roots. The results of multivariate statistical analysis showed that tuberous roots and fibrous roots could be significantly differentiated by the determination of soluble sugar fractions. The difference in sweetness values between tuberous roots and fibrous roots was small by conversion. CONCLUSION With high sensitivity, good precision and accuracy, GC-MS is able to distinguish a variety of soluble monosaccharides and disaccharides with similar structures, and realize the accurate characterization and quantification of a variety of soluble sugars in Ophiopohon japonicus, and providing a basis for the study of soluble sugar fractions in different parts of Ophiopohon japonicus and its further development and utilization.