OBJECTIVE To screen one Monascus purpureus stain that has high yield of lovastatin and provide potential strains for the development of red yeast rice(RYR) industry. OBJECTIVE Twelve RYR samples were collected, and Monascus sp. was isolated from these samples using traditional isolation technology and identified by morphology and ITS sequencing. All M. purpureus strains were screened and their total lovastatin contents [including lactone lovastatin(C₂₄H₃₆O₅) and acid lovastatin(C₂₄H₃₈O₆)] were determined by high performance liquid chromatography(HPLC). Soft SPSS 25.0 was used for variance analysis. RESULTS A total of 35 Monascus sp. strains were isolated and 23 of them were identified at specie level, including 11 M. purpureus strains, 10 M. ruber strains and 2 M. aurantiacus strains. There was significant difference(P<0.05) in lovastatin production among 11 M. purpureus strains. Among them, SM-1 isolate produced the highest amount of total lovastatin, with the value reaching (4.652±0.001) mg·g^-1, followed by M4-1, F1-3, and F5-3 strains with the value reaching (2.903±0.033) and (3.108±0.009) mg·g^-1, respectively. M4-5 isolate produced the lowest amount of lovastatin with the value of (2.712±0.014) mg·g^-1. CONCLUSION Fungal strain is chaotic in the fermentation of RYR on the market. A high-yielding lovastatin strain SM-1 is screened and can be used a potential strain for RYR production.

Rheumatoid arthritis(RA) is a chronic, systemic, and abnormal inflammatory immune response. It is characterized by the involvement of synovium and multiple organs and the destruction of joints and articular cartilage. In the past 30 years, some promising new compounds and antibodies have been developed to treat RA. The introduction of RA therapeutic drugs and the development of precision medicine have also given rise to several problems related to patients' access to new treatments, choice of the best regimen, cost-effectiveness, prognosis monitoring and efficacy monitoring, especially in terms of low drug response rate, drug resistance and adverse side effects. People attach great importance to the best combination of drugs for the treatment of RA, especially in patients with severe symptoms or early progression. New treatments and mechanisms are needed to solve these problems, and accurate guidelines for drug selection and drug recombination are established. According to the clinical trial database of the National Library of Medicine, this study summarizes the exciting new drugs, and discusses the trends and challenges in the development of RA drugs, which provides a meaningful reference for the accurate treatment and future research direction of RA.

OBJECTIVE To analyze the quality differences of Cyathulae Radix from different manufacturers on the market based on national drug sampling and testing in 2022, then analyze the problems and put forward suggestions to provide basis for the quality supervision and standard improvement of Cyathulae Radix. OBJECTIVE Inspection was conducted according to corresponding standards, inspection reports were issued, and then quality evaluation and analysis were conducted. At the same time, problems were found and suggestions were made based on targeted exploratory research on quality problems, standard problems and other related problems found in the inspection. RESULTS A total of 334 batches of Cyathulae Radix samples were taken. According to the standard inspection, two batches of samples were found to be substandard in character, and Cyathulae capitatae Radix was used as Cyathulae Radix. At the same time, it was found that the content determination methods in the standard were too complex, and the specified limit for content determination was too low. In the exploratory study, the unique component achybidensaponin I was detected in 27 batches of Cyathulae Radix and 7 batches exceeded the specified limit, which was mixed with Achyranthes bidentata. Plant growth regulator (paclobutrazol) was detected in 270 batches of Cyathulae capitatae Radix. The detection of heavy metals and harmful elements cadmium(Cd) in 114 batches exceeded the limit. Finally, the quality standard of Cyathulae Radix was improved, the supplementary test method was established, and the risk warning was put forward. CONCLUSION Through the national sampling inspection, the relevant problems in the prepared slices and quality standards of Cyathulae Radix are found, suggesting that the quality standards should be improved and the quality supervision of Cyathulae Radix should be strengthened.

OBJECTIVE To verify the accuracy of the “water content-conductivity fitting curve” model for determining the critical point of microemulsion O/W phase, and to further use this model to optimize the microemulsion of tanshinone extract. OBJECTIVE The “water content-conductivity fitting curve” model was used to determine the phase critical point of microemulsion into O/W type. According to the proportion of microemulsion oil phase, total surfactant and water phase, the pseudo ternary was drawn using Origin 2021 software. The phase diagram was used to screen out the proportions of the larger milk-forming areas; the average particle size and PDI of the microemulsion were used as the inspection indicators, and the star point design-response surface method was used to optimize the microemulsion; high-speed centrifugation and standing at 4 ℃ and 25 ℃ for 60 days, to examine the stability of the microemulsion. RESULTS The optimized microemulsion formulation was(18.11% medicated oil phase, 61.21% Tween 80, 20.68% 1,2-propanediol, the water critical point is 64.29%), K_m was 2.96, preparation temperature was 27.4 ℃, under different experimental conditions, the stability of the microemulsion was good. CONCLUSION The O/W phase critical point determined by the “water content-conductivity fitting curve” model has high accuracy, and the optimized microemulsion has good stability, which achieves the expected research goals.

OBJECTIVE To study the protective effect of petroleum ether fraction(AERP) and water soluble fraction(AERW) of Arnebia euchroma(Royle) Johnst. on acute liver injury in mice, and to isolate the effective components of petroleum ether fraction with better effect, and to study the antihepatitis B virus effect of its effective components. OBJECTIVE Forty eight C57 mice were randomly divided into 6 groups. After 14 days of administration, lipopolysaccharide/D-galactosamine(LPS/D-Galn) was used to induce acute liver injury with inflammatory infiltration at the last 2 hours. The liver and spleen index, the content of AST and ALT in mouse serum and the content of NO in liver homogenate were measured, and the pathological section of liver tissue was investigated. The petroleum ether extract was separated by normal silica gel, reverse silica gel and thin layer preparation plate, and four active naphthoquinones were obtained. The antihepatitis B virus activity of the four active naphthoquinones on HepG2.2.15 cells was detected by MTT method. RESULTS Both AERW high-dose group and AERP low-dose group can reduce the activity of AST and ALT in serum and the content of NO in liver tissue of mice to varying degrees, and improve the pathological changes of liver tissue to varying degrees. After comparative analysis, AERP has better liver protective and anti-inflammatory effects. The extraction method of AERP was optimized to obtain AERP with more effective components, and four active naphthoquinones were isolated: isovalerylshikonin, acetylshikonin, 2,3-dimethylpentenylshikonin and shikonin. Four active naphthoquinones have good inhibitory effects on HepG2.2.15 cells. CONCLUSION The results show that AERW and AERP have a good protective effect on acute liver injury. The liver protective effect of AERP is better than that of AERW. The four active components of AERP have a good inhibitory effect on HBV. AER extract has a significant liver protective effect, and the active components of AER have a significant inhibitory effect on hepatitis B virus.

OBJECTIVE To synthesize p-toluenesulfonic acid(PTS) and famotidine(FMT) cocrystal in order to improve thesolubility of famotidine in water and the permeability. OBJECTIVE The cocrystal was prepared by solvent evaporation method combined with ultrasound. The cocrystal was characterized by scanning electron microscopy, differential scanning calorimetry, thermogravimetric analysis, infrared spectroscopy and powder X-ray diffraction. The single crystal structure of FMT-PTS-H₂O(1∶1∶1) was successfully obtained, and the solubility and permeability of the newly synthesized cocrystal were studied. RESULTS After the formation of cocrystal, the water solubility and permeability of FMT increased by 1.54 and 2.29 times, respectively. CONCLUSION Compared with FMT, the solubility and permeability of FMT after the formation of cocrystal were improved. This study provides a method for improving the permeability of biopharmaceutics classification system(BCS)Ⅲ drugs, which will contribute to the development of low permeability drugs.

OBJECTIVE To investigate the effect of 717 Jiedu decoction on neutrophil extracellular traps (NETs) and CYR61/CCN1 expression in local tissue of rats after Agkistrodon halys bite. METHODS SD rats were randomly divided into normal control group, Agkistrodon halys bite group and high-dose and low-dose 717 Jiedu decoction groups. The serum and thigh gastrocnemius were collected, and the pathological changes of gastrocnemius in each group were observed by Hematoxylin-Eosin staining(HE) and Masson staining, the ultrastructure of gastrocnemius in each group was observed by transmission electron microscopy, the apoptosis of gastrocnemius cells in each group was detected by TUNEL method, and the serum circulating-free cell (cf-DNA) level was detected by PicoGreen fluorescence. The expression levels of myeloperoxidase (MPO) in serum and gastrocnemius were detected by enzyme-linked immunosorbent assay(ELISA), the change of neutrophil elastase (NE) in gastrocnemius was detected by immunohistochemistry, and the level of citcitinic histone H3 (CitH3) in gastrocnemius was detected by immunofluorescence. The expressions of CYR61/CCN1 protein and its mRNA in gastrocnemius were detected by Western blot and PCR. RESULTS Compared with the normal group, the model group showed significant inflammatory infiltration and bleeding reaction, and the degree of collagen fibrosis increased. Ultrastructure showed that the structure of gastrocnemius cells in the model group was seriously damaged, and the distribution of muscle segments was asymmetrical. The contents of cf-DNA and MPO in serum were significantly increased (P<0.01), the protein expressions of MPO and CitH3 in gastrocnemius were increased (P<0.05 or P<0.01), and the protein and mRNA expressions of CYR61/CCN1 in gastrocnemius were up-regulated. All the administration groups of 717 Jiedu decoction significantly improved the local inflammatory response and bleeding symptoms of rats, reduced the degree of collagen fibrosis, effectively inhibited the apoptosis rate of gastrocnemius cells of pit viper bitten rats, and reduced the contents of cf-DNA and MPO in serum (P<0.05 or P<0.01). The expressions of NE and MPO in gastrocnemius were inhibited in the high-dose 717 Jiedu decoction group, and the expression of CitH3 in gastrocnemius muscle was decreased in all administration groups of 717 Jiedu decoction (P<0.05 or P<0.01), and the high expression of CYR61/CCN1 protein and its mRNA was inhibited. CONCLUSION The venom of Agkistrodon halys can induce the formation of neutrophil NETs in local tissue and the overexpression of CYR61/CCN1. The 717 Jiedu decoction could improve the ultrastructure of gastrocnemius muscle and inhibit cell apoptosis, which may also improve snitch symptoms by regulating the NETs-Cyr61/CCN1 pathway. The signaling molecules of NETs and CYR61/CCN1 are expected to be new targets for the prevention and treatment of local tissue damage caused by Agkistrodon halys venom.

OBJECTIVE To establish the fingerprint of the substance benchmark of Qianghuo shengshi decoction (QSD) and the determination method of multi-index composition content, study the transfer rule of the substance benchmark value of QSD, and provide a scientific basis for the subsequent development of QSD and quality control evaluation. METHODS Fifteen batches of QSD substance benchmark samples were prepared according to the method recorded in ancient medical books, and their fingerprint was established and evaluated, its characteristic peaks was clarified and assigned to the characteristic peaks, and we complete the content determination and transfer rate calculation of the 8 index components in the QSD substance benchmark. RESULTS The similarity of the fingerprint of 15 batches of QSD substance benchmark was between 0.882 and 0.938. A total of 24 common peaks were identified, and 8 common peaks were identified as chlorogenic acid, prim-O-glucosylcimifugin, ferulic acid, senkyunolide I, 5-O-methylvisammioside, ammonium glycyrrhizinate, notopterygol, osthole. The paste yield of 15 batches of QSD was 22.54%-29.92%, and the average paste transfer rate was 70.69%. The content and average transfer rate of each index component from decoction pieces to substance benchmarks were 0.077 2%-0.106 6% and 128.05% for chlorogenic acid,prim-O-glucosylcimifugin 0.015 5%-0.023 8% and 120.26%, ferulic acid 0.047 5%-0.076 0% and 114.49%, senkyunolide I 0.006 6%-0.008 9% and 132.93%, 5-O-methylvisammioside 0.007 2%-0.009 9% and 90.27%, ammonium glycyrrhizinate 0.181 6%-0.273 5% and 80.53%, notopterygol 0.000 7%-0.001 3% and 50.97%, osthole 0.000 9%-0.002 2% and 13.67%. CONCLUSION In this experiment, a combination of fingerprint, paste yield and multi-index composition content determination could be used to analysis the transfer rate of QSD decoction pieces to substance benchmarks, and provide a method reference for the quality control and subsequent development of this prescription.

OBJECTIVE To investigate the effects of different drying methods on the concentrates of Astragalus membranaceus and provide a basis for the optimization and establishment of their drying processes. METHODS The contents of Astragalus methyloside, Pistil isoflavone glucoside, Pistil isoflavone, Mangiferin, Astragalus polysaccharide, ethanol extract and the clarity index and solubility index were used as evaluation indexes to dry Astragalus concentrate by freeze-drying, vacuum drying, atmospheric pressure drying and microwave drying, and the weights of each index were jointly determined by hierarchical analysis (AHP) and entropy weighting method, and the most suitable drying method was selected by the combination of comprehensive scoring, cluster analysis, fingerprinting and other methods as well as the characteristics of each drying method itself. RESULTS The effects of different drying methods on the concentration of Astragalus membranaceus varied widely, with the highest comprehensive scores for freeze-drying and vacuum-drying and lower scores for atmospheric-pressure drying and microwave drying. According to the analysis of similarity evaluation software, the fingerprint profiles of freeze-dried and vacuum-dried samples were the most similar to those of concentrates, the differences between the samples obtained from the two drying methods were small, and the results were similar to the comprehensive scores. Within the experimental range, the concentrates of Astragalus membranaceus were more stable under freeze-drying and vacuum-drying conditions. CONCLUSION The effect of different drying methods and conditions on Astragalus concentrates varies greatly. Through the study of four drying methods, vacuum drying is finally selected as the most suitable drying method for Astragalus concentrates.

OBJECTIVE To investigate the non-clinical safety and immunogenicity of recombinant group B meningococcal vaccine by repeatedly dose to rats, so as to provide reference for designing dose level and monitoring toxicity and side effects in clinical trials. METHODS SD rats were used to design 4 main toxicity groups including negative control group, adjuvant control group, low dose vaccine group (1 dose each) and high dose vaccine group (3 doses each) and 3 satellite groups. The vaccine was dosed by intramuscular injection at weeks 0, 3, 6, 9 and 12 respectively. During the study, all the animals of the main toxicity group were observed for clinical signs, indicators such as body weights, food consumption, body temperature, blood cells counting, coagulation, serum biochemistry, ophthalmology, T lymphocyte subsets and cytokines were detected. Serum specific IgG antibody and bactericidal antibody were measured for satellite animals. All the animals were observed anatomically, main organs were weighed to the calculate viscera/body ratio and the viscera/brain ratio, and various tissues and organs were examined pathologically. RESULTS It could produce high-leveled binding antibodies and bactericidal antibodies with strong activity in immune serum that rats injected the low and high doses of recombinant group B meningococcal vaccines. Both the low and high dose vaccines caused the increases in neutrophils, monocytes and lymphocytes significantly, the decreases in hemoglobin and RBC significantly. Other dose-related changes involved the increase in serum globulin and decrease in albumin, with concomitant decrease in A/G, which basically returned to normal after 4 weeks of recovery period. The histopathological findings associated with adjuvant and vaccine were mild or moderate granulomatous inflammation, acute inflammation in injection site, infiltration and proliferation of mononuclear cells/mixed cells in the sciatic membrane, and increased number of myeloid plasma cells and granulocytes in lymph nodes. CONCLUSION Recombinant group B meningococcal vaccine had good immunogenicity and safety profile in SD rats, there is no immune toxicity reaction. It is obvious that adjuvant and vaccine-related changes in indicators of peripheral blood and the inflammation response in injection site. Under the dose levels of this study, there is no adverse effect level on recombinant B group meningococcal vaccine for 3 doses/one rat.