OBJECTIVE To investigate the secondary metabolites and bioactivities of the mangrove Rhizophora stylosa derived fungus Diaporthe sp. SCSIO 41011. METHODS Various modern chromatographic methods were subjected to isolate and purify the fermentation products of the strain. The chemical structures of the obtained compounds were identified by nuclear magnetic resonance technology as well as literature data. The antibacterial activity, NF-κB luciferase inhibitory activity, and antioxidant activity of the compounds were determined. The antioxidant activity of the compounds was determined by 1,1-diphenyl-2-picrylhydrazy (DPPH) and ferric reducing ability of plasma (FRAP). RESULTS Seven compounds (1-7) were isolated from the fermentation products and were identified as nigrosporapyrone D (1), vermopyrone (2), tyrosol (3), 2-(2-hydroxyethyl)phenol (4), 3-phenylpropane-1,2-diol (5), 4-hydroxyphenethyl acetate (6), 2-hydroxyphenethyl acetate (7). The chemical structure of 2 was confirmed by X-ray single-crystal diffraction method for the first time herein. At the concentration of 1 mg·mL^-1, the FRAP values of compounds 3, 6, and 7 were 208.75, 160.03, and 162.75 μmol·L^-1, respectively. CONCLUSION Two pyranones (1 and 2) and five phenolic compounds (3-7) are characterized from the fungus, meanwhile compounds 1, 2, 4, 5, and 7 are isolated from the Diaporthe genus for the first time. And compounds 3, 6, and 7 show iron ion reduction/antioxidant capacity. This study would enrich the structural diversity of secondary metabolites of Diaporthe sp., and lays a foundation for further study on the natural products of mangrove endophytic fungi.

OBJECTIVE To optimize the spray drying process of Ejiao zaoqi water extract concentrate, and to measure the physical fingerprint of spray drying extract powder. METHODS The powder yield, calycosin-7-O-β-D-glucopyranoside transfer rate, hesperidin transfer rate and extract moisture content were used as evaluation indexes, and the AHP-entropy weight method was used to weight, and the spray drying process was optimized by Plackett-Burman test combined with Box-Behnken response surface method. Twelve secondary physical indexes of micromeritic properties, such as moisture content and bulk density of spray dried extract powder, were determined, and the physical fingerprints was determined for similarity analysis. RESULTS The optimal spray drying conditions were as follows: liquid concentration of 0.25 g·mL^-1, addition of dextrin 5.0 g·100 mL^-1, air inlet velocity of 0.41 m³·min^-1, air temperature of 140 ℃, injection speed of 10 mL·min^-1, temperature of liquid 60 ℃, and gun pressure of 0.4 MPa. The similarity of the physical fingerprints of the 10 batches of detection powder was greater than 0.9. CONCLUSION The spray drying process of the selected Ejiao zaoqi water extract concentrate is stable and feasible, which can provide a basis for the research and development of this preparation.

OBJECTIVE To investigate the imatinib mesylate (IM) adherence and health-related quality of life (HRQoL) of gastrointestinal stromal tumor (GIST) patients, and further identify the influencing factors. METHODS Patients who visited the GIST specialty clinic between April 2022 and April 2024 were enrolled. All eligible patients completed a composite questionnaire, including the basic situation, adherence, HRQoL, and adverse events. Then the influencing factors of adherence and HRQoL were analyzed. RESULTS A total of 227 GIST patients were enrolled, and the IM adherence rate was 48.5%. The main non-adherence factors were living in rural area for extended periods, concomitant disease, without therapeutic drug monitoring (TDM), impaired cognitive function, pain, dyspnea, insomnia, fatigue, and gastrointestinal adverse effects. Multivariate logistic regression analysis showed that TDM and no pain were promoters of adherence. The risk factors for global health status were female, unemployment, monthly income less than 3000 yuan, concomitant medications and anemia, and such patients had lower functioning score and higher symptom burden. Multivariate logistic regression analysis showed that gender was a predictor of global health status. CONCLUSION Patients with GIST often exhibit low adherence to IM, and various factors can impact both adherence and HRQoL. In the future, medical workers can play a crucial role in providing medication education and guidance, adverse events management, TDM, and interventions for patients with specific risk factors to enhance IM adherence and overall well-being of patients with GIST.

Styrene-isoprene-styrene block copolymer pressure sensitive adhesive (SIS-PSA) is an ideal commercial adhesive with unique environmental attributes and high processability. As a key excipient for patches, SIS-PSA has a significant impact on the key properties such as drug release and adhesion. Since the performance of SIS-PSA is determined by a combination of different components, a thorough understanding of these components is essential for patch formulation design. This article discusses the impact of each component in SIS-PSA on the key performance of patches, summarizes the composition and application of marketed SIS-PSA patches, and focuses on patch formulation design oriented towards clinical needs, aiming to provide a reference for the research and development of SIS-PSA patches.

OBJECTIVE To investigate the fibrinolytic activity and protein profile change of Pheretima guillemi (Michaelsen)-derived anticoagulant proteins DPf3 after digestion in gastrointestinal tract in vitro and in vivo, and to predict the spatial structure of its active protein, DPf3 ID NO.2, by homology modeling. METHODS The in vitro digestive effects of pepsin (and trypsin) on DPf3 were investigated under simulated gastric empty state (pH 2) and semi-empty state (pH 5), and the in vivo digestion effects were evaluated via Kunming mice orally administrated DPf3. The activity and protein profile of DPf3 after hydrolysis in vivo and in vitro were analyzed by fibrin plate method combined with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE); I-TASSER combined with SAVES v5.0 were used to homology modeling and evaluate the structure of DPf3 ID NO.2, the active protein of DPf3, and to predict its secondary and tertiary structure. RESULTS After enzymatic hydrolysis in vitro, the fibrinolytic activity of DPf3 was lost under pH 2 incubation, and the fibrinolytic activity of DPf3 incubated with heat inactivated pepsin at pH 5 was slightly higher than that of DPf3 incubated with activated pepsin. After enzymolysis in vivo, only the fibrinolytic activity of gastric perfusion fluid was significantly different from that of control group. The protein profile showed that the stable presence of DPf3 ID NO.2 might be an important reason for the fibrinolytic activity of DPf3. Spatial structure prediction showed that DPf3 ID NO.2 was a typical chymotrypsin-like serine protease, revealing its catalytic center, zymogenic center, important amino acid residues and S1 active pocket. CONCLUSION The combination of in vivo and in vitro hydrolysis provide a basis for the protein expression profile and activity changes of antithrombotic protein DPf3 after oral administration. Homologous modeling is feasible for the structural prediction of active peptides in macromolecular proteins of the traditional Chinese animal medicine.

OBJECTIVE To construct a competency evaluation index system for clinical pharmacists. METHODS Based on previous research, the method of analytic hierarchy process was used to establish the evaluation hierarchy for competency of clinical pharmacists. A total of 20 experts were included, with an average age of (44.9±5.2) years and an average working seniority of (16.2±8.8) years. RESULTS The weight coefficients of 6 first class indictors, 18 secondary class indictors and 54 third class indictors were confirmed. The weight of each indictor was all consistent with the test. CONCLUSION This study preliminarily constructs a competency evaluation index system for clinical pharmacists, providing reference for the selection, evaluation, and training of clinical pharmacists, and further improvements are still needed.

OBJECTIVE To establish HPLC fingerprints of Centellae Herba and study the spectrum-effect relationship between its fingerprints and antioxidant activity, screen the quality markers of Centellae Herba and provide a basis for its quality evaluation. METHODS To establish the HPLC fingerprint of Centellae Herba and study the results of common peak area by combining cluster analysis and principal component analysis (PCA). The antioxidant activity of 16 batches of Centellae Herba samples was evaluated by the DPPH and ABTS radical scavenging methods and apply gray correlation analysis (GCA) and partial least squares regression (PLSR) to analyze the spectrum-effect relationship between Centellae Herba fingerprint and antioxidant activity. Network pharmacology technology was introduced to analyze the core targets and construct the network relationship, the compound and core target were verified based on molecular docking to comprehensively screen the active ingredients. RESULTS The similarity range of the fingerprints spectrum was 0.819-0.982, and a total of 9 common peaks were calibrated, 7 chemical components were identified. The 16 batches of Centellae Herba were divided into four categories, all of which had antioxidant capacity and were concentration-dependent. The results of spectral correlation analysis showed that the total peaks 1 (asiaticoside B), 2 (madecassoside) and 5 (kaempferol) were closely related to the antioxidant activity of Centellae Herba, among which asiaticoside B, madecassoside and kaempferol acted on 127 targets, and the key targets were SRC, ESR1 and HSP90AB1. Based on the five principles of Q-Marker, asiaticoside B, madecassoside, kaempferol and asiaticoside were finally determined as the evaluation indexes for quality control. CONCLUSION The spectral correlation analysis between different batches of Centellae Herba and antioxidant activity can provide a reference for the excavation and overall quality control of Centellae Herba.

Chronic kidney disease(CKD)is a major disease that seriously endangers human health and life, with high morbidity and mortality. It is an urgent problem to find effective treatment methods to control the development. many studies have found that intestinal flora and its metabolites are closely related to the occurrence and development of CKD. Curcumin(CUR)have been shown to be effective in acute kidney injury and CKD. However, CUR has extremely low bioavailability after oral administration and absorption, and the material basis and process mechanism of its pharmacological effects have been controversial. In recent years, the regulatory effect of CUR on intestinal microecology has been extensively studied. It has been reported that high concentrations of CUR exist in the gastrointestinal tract after oral administration, which may mainly play a direct regulatory role in the gastrointestinal tract. Furthermore, a newly proposed theory suggests that CUR may exert its renal protective effects indirectly by affecting the “gut-kidney axis”. Therefore, this review will mainly discuss the close relationship between gut microbiota and its metabolites with CKD, and the therapeutic strategies of CUR targeting gut microbiota to improve CKD, including regulating the composition of gut microbiota, protecting the intestinal mucosal barrier, regulating intestinal inflammatory signal transduction, increasing the content of short-chain fatty acids(SCFAs), and enhancing of gut microbiota-mediated biotransformation of CUR. The future prospect is assessed by us that the metabolites of CUR and microorganisms can beneficially delay the onset and progression of CKD by targeting the intestinal flora and propose the unresolved scientific issues in this area.

OBJECTIVE To determine the xanthine oxidase (XO) inhibitory activity of Phellodendri Chinensis Cortex based on electrochemical biosensor to establish the evaluation method for anti-gout biological potency and compare the quality combined with chemical content determination, thus to provide a new model of overall quality assessment of Phellodendri Chinensis Cortex. METHODS The contents of berberine and phellodendrine in Phellodendri Chinensis Cortex samples were determined by high performance liquid chromatography (HPLC). The anti-gout biological potency was investigated by electrochemical biosensor. And Pearson correlation analysis was used to calculate the correlation between biological potency and chemical components of Phellodendri Chinensis Cortex. RESULTS The chemical content of Phellodendri Chinensis Cortex in each batch met the requirements of the Chinese Pharmacopoeia 2020: the content of berberine was 5.09% to 34.76%, and the content of phellodendrine was 2.56% to 4.76%. The XO inhibitory activity of Phellodendri Chinensis Cortex samples varied greatly, and their biological potency ranged from 25.60 to 337.96 U·mg^-1. In addition, Pearson correlation analysis showed that there was no significant correlation between berberine and phellodendrine contents and their anti-gout biological potency (P>0.05). CONCLUSION The established biological potency evaluation method with electrochemical biosensor can be used for the quality test of Phellodendri Chinensis Cortex, and the combination of chemical composition and biological potency can reflect the quality difference among Phellodendri Chinensis Cortex batches more objectively and reasonably.

The RNA-dependent RNA polymerase (RdRp) of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) plays a pivotal role in the virus's replication process and is a primary target for nucleoside analogue antiviral drugs. However, the ongoing mutations of the virus have led to the emergence of multiple variants of concern, such as Alpha, Beta, Gamma, Delta, and Omicron, resulting in recurrent waves of the pandemic that are yet to be fully controlled. Although the RdRp of the novel coronavirus is relatively conserved, ongoing research has identified several mutations at this protein, such as V166A, V166L, and P323L. The impact of these mutations on the antiviral efficacy of currently available small molecule drugs is noteworthy. This article reviews the influence of SARS-CoV-2 RdRp mutations on resistance to remdesivir, incorporating protein structure prediction of the mutation sites, with the aim of providing insights for optimizing antiviral treatment strategies against COVID-19.