Ovarian cancer is a malignant tumor with a high mortality rate in women. PARP inhibitors (poly ADP-ribose polymerase inhibitors, PARPi), as one of the mainstays of maintenance therapy, can significantly improve the survival rate of patients; however, with the widespread use of PARPi, PARPi resistance has become an urgent problem in the treatment process. Current studies have found that metabolic reprogramming in the tumor microenvironment (TME) may affect chemoresistance in ovarian cancer through multiple mechanisms, but whether lipid metabolic reprogramming in the TME is involved in the formation of PARPi resistance is not clear. The aim of this paper is to explore the effect of lipid metabolism in TME on PARPi resistance in ovarian cancer in recent years and to analyze the possible link between it and PARPi resistance, with a view to providing new perspectives for further understanding the mechanism of PARPi resistance formation and searching for new therapeutic targets.

Long-acting injectable formulations are preferred over conventional formulations for the treatment of chronic diseases. An effort to build the relationship between an in-vivo property of a dosage form and an in-vitro response is often referred to as“in vitro-in vivo correlation” (IVIVC) analysis. This paper provides an overview of the classification, establishment and evaluation method of IVIVC. Due to long-acting injectable formulations' diverse nature, it is impractical to establish an universal IVIVC model in vitro, it is essential to develop individual IVIVC model in every study. Integrated knowledges of physicochemical, dosage form design and the interaction of the drug molecule with site of administration play important roles in the study of long-acting injectable formulations' IVIVC.

OBJECTIVE To investigate the secondary metabolites and hypolipidemic properties of Irpex lacteus. METHODS Compounds were isolated and purified using silica gel column chromatography, preparative high-performance liquid chromatography (Pre-HPLC), and other chromatographic techniques. Structural identification was performed through nuclear magnetic resonance (NMR), high-resolution mass spectrometry, infrared (IR), and ultraviolet (UV) spectroscopy. HepG2 cell model with high lipid was established to test the hypolipidemic activity. RESULTS Twelve compounds were isolated from Irpex lacteus and identified as (2α, 4β, 5β, 7β, 10α)-2, 5, 11-eudesmanetriol(1), 11, 12-epoxy-5, 6-secotremula-1, 6(13)-dien-5-12-olide(2), 8α, 10α-di-O-acetyl-lactarorufin A(3), (+)-(2S, 3R, 6S, 7S)-tremul-1(10)-ene-2, 12- diol(4), conocenolide A(5), irpexolactin G(6)、2, 2'-oxybis(1, 4-di-tert-butylbenzene) (7), 4'-hydroxy-5, 7-dimethoxy-6-(3-methyl-2-butenyl)- isoflavone(8), cyclo(Ile-Val) (9)、cyclo(L-Pro-L-Leu) (10), cyclo(Ile-Leu) (11), cyclo(Ile-lle) (12). The results of hypolipidemic activity showed that compounds 1-4, 8 and 9 had hypolipidemic activities, and the reduction effect of TG content in each dose group of compounds 1, 4 and the high and medium dose groups of compounds 2, 3 and 8 was better than that of the positive drug group. CONCLUSION Compounds 1-4, 7-12 are isolated from this strain for the first time. Compounds 1-4, 8 and 9 have good hypolipidemic effects.

OBJECTIVE To ensure the equivalence of the ancient and modern processes, and optimize the alcohol extractionprocess of Erxian Decoction(EXD), using standard relation andanalytic hierarchy process(AHP)-entropy weight method combinedwith Box-Behnken response surface method. METHODS Taking phellodendrine, mangiferin, ferulic acid, berberine, curculigoside, epmedin A1, epmedin A, epmedin B, epmedin C, icariin content, dry extract rate and fingerprint similarity as the key quality factors, taking ethanol concetration, solid-liquid ratio and extraction time as the key process parameters, the best extraction process was obtained by Box-Behnken response surface method. RESULTS The optimal conditions were 75% ethanol, 1∶14 solid-liquid ratio (g∶mL) and 62 min extraction time. The verified experimental results showed that the average comprehensive score was 86.64, and the relative standard deviation(RSD) was 1.02%. CONCLUSION The alcohol extraction process of EXD is optimized using standard relation combined with AHP-entropy weight method, the fitted model is significant, and the quality of the standard decoction is highly consistent, which provids a reference for the change of dosage form in the later stage.

OBJECTIVE To establish UPLC fingerprint of Aster tataricus cv.Qiziwan, identify the compounds of common peaks by UPLC-Q-TOF-MS technology, determine antioxidant activity of each batch and study the relationship between effects of antioxidant and spectrum of Aster tataricus cv.Qiziwan. METHODS The fingerprints of 22 batches of Aster tataricus cv.Qiziwan were drawn and evaluated by the the Similarity Evaluation System of TCM Chromatographic Fingerprint (2012 edition), and the common peaks were calibrated. The antioxidant activity of Aster tataricus cv.Qiziwan was investigated by using the free radical scavenging rate of 1, 1-diphenyl-2-picryl-hydrazyl (DPPH) and 2, 2'-azinobis- (3-ethylbenzthiazoline-6-sulphonate) (ABTS) free radical scavenging rate as the antioxidant index. The spectral effect relationship between chemical constituents and antioxidant activity of Aster tataricus cv.Qiziwan was analyzed by grey correlation degree and partial least squares regression. RESULTS The fingerprints of 22 batches of Aster tataricus cv.Qiziwan from different batchs were established, and the similarity was 0.892-0.995. Cluster analysis can distinguish rhizome with mother root, root and rhizome. Seventeen common peaks were identified by comparison of reference materials and UPLC-MS analysis. The DPPH free radical and ABTS free radical scavenging experiments showed that 22 batches of Aster tataricus cv.Qiziwan had antioxidant capacity, and the grey correlation analysis showed that shionone had the highest correlation degree. Combined with partial least squares regression analysis, it was preliminarily confirmed that rutin, ferulic acid, isochlorogenic acid A, astin A, quercetin, perillen and shionone were the main components of Aster tataricus cv.Qiziwan with antioxidant activity. CONCLUSION In this study, the fingerprint and antioxidant activity spectrum effect relationship of Aster tataricus cv. Qiziwan are successfully established, which can provide reference for the pharmacodynamic material basis research and quality control of Aster tataricus cv.Qiziwan.

OBJECTIVE To investigate the role and mechanism of phellopterin in preventing breast cancer metastasis. METHODS The cytotoxicity of phellopterin was evaluated by CCK-8 assay and flow cytometry for cell cycle and apoptosis. The effect of phellopterin on the adhesion between cancer cells and vascular endothelial cells was detected by immunofluorescence. The effect of phellopterin on the expression of cell adhesion molecules (CAMs) on the surface of HUVECs was detected by flow cytometry. The effect of phellopterin on the expression of epithelial-mesenchymal transition(EMT) regulatory proteins in cancer cells was detected by Western blot and quantitative real-time reverse transcription polymerase chain reaction(qRT-PCR). The inhibitory effect of phellopterin on lung metastasis of breast cancer in mice was evaluated by a mouse cancer metastasis model. RESULTS Phellopterin exhibits relatively low cytotoxicity and can inhibit the adhesion of cancer cells to HUVECs by reducing the expression of CAMs, such as vascular cell adhesion molecule-1(VCAM-1), intercellular cell adhesion molecule-1(ICAM-1), and E-selectin, which are induced by the inflammatory factor TNF-α. Additionally, phellopterin suppresses the expression of regulatory factors associated with EMT transformation and metastasis-promoting proteins, including tripartite motif containing 22(TRIM22), thrombospondin-1(THBS1), and KIT ligand(KITLG). In a mouse model of cancer metastasis, phellopterin was shown to significantly inhibit breast cancer lung metastasis and enhance the activity of anti-tumor immune cells (cytotoxic T lymphocytes and natural killer cells) in peripheral blood. CONCLUSION Phellopterin shows a significant preventive effect on breast cancer metastasis and holds substantial potential for further development and application.

OBJECTIVE To investigate the distribution of prevalent traditional Chinese medical syndromes associated with bortezomib-related peripheral neuropathy(BiPN), the efficacy of Guicao Baidu(GCBD) decoction combined with a PD(bortezomib combined with dexamethasone)-based regimen in the treatment of BiPN patients, and the likely mechanism. METHODS A retrospective analysis of the clinical data of 17 myeloma patients with peripheral neuropathy associated with bortezomib was conducted. Peripheral neuropathy of varying degrees was observed in these individuals following a bortezomib-based regimen administered from January 2019 to December 2023. Symptom score scale was formulated for the objective BiPN syndrome differentiation. Peripheral neuropathy was evaluated using the National Cancer Institute's Common Toxicity Criteria for Adverse Events(NCI-CTCAE). GCBD decoction was administered orally. The effectiveness was assessed by looking at the visual analogue scale(VAS) score, neuroelectrophysiology, tumor treatment function evaluation/gynecological tumor group neurotoxicity subscale(FACT/GOG-Ntx) score, and NCI-CTCAE grade. The possible ingredients and targets of GCBD decoction in intervening BiPN were then predictd using mass spectrometry analysis and network pharmacology approaches. Molecular docking technology was utilized to confirm the binding activity between GCBD decoction's components and targets, while gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) enrichment analysis were employed to investigate its mode of action. Furthermore, nerve growth factor(NGF)-induced PC12 cells were employed to generate a BiPN cell model. By assessing cell viability, reactive oxygen species(ROS) levels, neurite length, apoptosis levels, mitochondrial number, mitochondrial membrane potential, apoptotic protein expression, and mitochondrial translocation of BAX, the therapeutic mechanism of GCBD decoction was identified. RESULTS The syndrome differentiation types of BiPN patients were characterized mostly by qi and blood shortage, yang deficiency, cold coagulation, and blood stasis. GCBD decoction substantially reduced BiPN, peripheral neuropathy(PN) grade, FACT score, and VAS score(P<0.01 or P<0.05). Network pharmacology analysis obtained 3541 potential targets for GCBD decoction to interfere with BiPN, among which apoptotic proteins such as BCL2-Associated X (BAX), P53, B-cell lymphoma-2 (BCL-2), and Caspase-3 (CASP3) were the core targets. The GO and KEGG pathway enrichment indicated that one of the key pathways through which GCBD decoction intervened in BiPN was mitochondrial apoptosis. It was shown by molecular docking that several GCBD decoction monomers exhibited strong docking activity with the mitochondrial apoptotic proteins BAX, BCL-2, and CASP3. CONCLUSION This study preliminarily explors the TCM syndrome differentiation of BiPN patients, reveals the mechanism of GCBD decoction in inhibiting mitochondrial apoptosis and improving BiPN, and provids new ideas for reducing the toxic and side effects of chemotherapy in clinical practice.

OBJECTIVE This study aims to establish and characterize patient-derived colorectal cancer organoid models and evaluate their potential value in predicting chemotherapy responses through individualized drug sensitivity testing. METHODS Tumor tissues were obtained from surgical specimens of three patients who underwent radical surgery for colorectal cancer. Tumor cells were isolated through mechanical and enzymatic dissociation, and the resulting cell suspension was mixed with Matrigel and seeded into a three-dimensional culture system. The histopathological characteristics of the organoids were validated using hematoxylin-eosin (HE) staining and immunohistochemistry, and their genetic consistency was confirmed by short tandem repeat (STR) analysis, demonstrating that this model could reflect both intra- and inter-patient tumor heterogeneity. Standard clinical chemotherapy regimens were applied to the organoid models, and drug sensitivity was assessed using the CellTiter-Glo^® 3D cell viability assay. RESULTS The cultured colorectal cancer organoids closely resembled their originating tumors in terms of histopathological and genetic characteristics. Drug sensitivity testing indicated that organoids derived from different patients exhibited varied sensitivities to commonly used chemotherapeutic agents. CONCLUSION The colorectal cancer organoid model successfully established in this study closely recapitulates the histological classification and genetic features of the parent tumors and shows potential for application in vitro chemotherapy sensitivity testing. This model could be used to predict colorectal cancer patients’ responses to chemotherapy, providing valuable reference for personalized medicine.

OBJECTIVE To prepare carvacrol (CAR) mixed micelles with temperature-responsive characteristics, optimize the preparation process, and evaluate their properties. METHODS CAR mixed micelles were prepared using the thin-film dispersion method with vitamin E polyethylene glycol 1000 succinate (TPGS) and poly(N-isopropyl acrylamide) (PNIPAM) as carrier materials. The analytic hierarchy process (AHP)-variation coefficient method was employed to assign weights to individual indicators, yielding an overall desirability (OD) score as an evaluation parameter. This score was combined with the response surface method (RSM) to optimize the CAR mixed micelles preparation process, followed by characterization of their physicochemical properties. RESULTS The optimal conditions for preparing CAR mixed micelles were determined as follows: the mass ratio of TPGS to PNIPAM was 9∶1, the amount of carrier was 11 mg, the hydration medium was ultrapure water, the hydration temperature was 50 ℃, the hydration volume was 9.48 mL, and the hydration time was 1 hour. Validation testing showed that the critical micelle concentration (CMC) of CAR mixed micelles was 0.025 mg·mL^-1, the encapsulation efficiency was (86.36±2.29)%, the drug loading was (5.54±0.53)%, the particle size was (19.83±1.69) nm, the polydispersity index (PDI) was (0.242±0.080), and the Zeta potential was (-0.105±0.046) mV. The calculated OD value was (87.72±1.03)%, closely approximating the predicted value (86.92%), indicating reliable prediction. The CAR mixed micelles exhibited a spherical shape, uniform distribution without aggregation, and demonstrated good stability. Fourier transform infrared spectroscopy and differential scanning calorimetry confirmed the CAR's presence within the mixed micelles. Temperature sensitivity tests revealed that the CAR mixed micelles had a lower critical solution temperature (LCST) of 37.64 ℃, indicating their temperature-responsive properties. CONCLUSION The optimized CAR mixed micelles exhibit excellent stability and temperature sensitivity, providing a solid experimental foundation and reference for future formulation research.

OBJECTIVE To prepare chitosan (CS)/sodium alginate (SA) hydrogel (GelCA@LUT) loaded with luteolin (LUT) nanoparticles (NPs@LUT) as a wound dressing and evaluate its physicochemical properties, as well as its safety. METHODS NPs@LUT were prepared by an emulsion-solvent evaporation method, and hydrogels (GelCA) with different contents of cross-linking agents (genipin) and different CS/SA quality ratios were prepared. Then, the wound dressing (GelCA@LUT) was obtained by coating NPs@LUT on the surface of GelCA. The properties of the hydrogel were evaluated by measuring water vapor transmission rate, water content, water retention, swelling properties, porosity, and rheological properties. The structure and morphology of the hydrogel were characterized using Fourier transform infrared spectroscopy (FTIR), transmission (TEM), and scanning electron microscopy (SEM). The release profiles of LUT from NPs@LUT and GelCA@LUT was examined in different concentrations of hydrogen peroxide/PBS buffer; hemocompatibility and cytotoxicity were tested by hemolytic and cytotoxicity assays, respectively. RESULTS The characterization results showed that the average particle size of NPs@LUT was (234.3±4.7) nm, the drug loading rate was (9.54±0.10)%, and the encapsulation efficiency was (85.35±0.95)%. GelCA with a mass ratio of CS to SA at 1∶2 and a cross-linking agent dosage of 1.0 mg was successfully constructed. Both NPs@LUT and GelCA@LUT could release LUT stably, and GelCA@LUT had good biocompatibility. CONCLUSION GelCA@LUT can accelerate wound regeneration by substantially improving the wound microenvironment.

OBJECTIVE To construct a scoring card capable of distinguishing between wild, semi-wild, and cultivated Astragali Radix. METHODS Six hundred batches of virtual data generated by TVAE deep learning were used as the training and validation sets. The training set data were binned, and the bins were adjusted and optimized to calculate the weight of evidence (WOE) for each bin. The data were encoded using WOE, and a logistic regression model was established. The model was trained on the training set and tuned using the validation set. A score of 50 was set as the threshold where the sample's positive and negative classification probabilities are equal. The baseline score and the scores corresponding to each bin were calculated using the formula and the logistic regression model equation. The sample score was determined by adding the base score and the scores corresponding to each bin for the sample, with a threshold of 50 used to judge the probability of the sample's positive or negative category. Card A and Card B were constructed to discriminate whether the Astragali Radix sample is wild or cultivated, respectively. RESULTS Sixty-four batches of real sample data were used as the test set to evaluate Card A and Card B, with classification accuracy rates of 0.86 and 0.80, respectively. CONCLUSION The scoring card can accurately discriminate the source of Astragali Radix samples, and the model is stable, reliable, easy to operate, and easy to promote.

OBJECTIVE To investigate the characteristics of severe cutaneous adverse reactions (SCARs) induced by proton pump inhibitors (PPIs) and provide references for clinical safe use of drugs. METHODS Case reports of SCARs caused by PPIs were retrieved from Pubmed, CNKI, Wanfang and VIP databases up to June 2024. Information such as demographic characteristics, drug use, occurrence time, types, clinical manifestations, treatment measures and outcomes of patients was collected, and descriptive statistical analysis was conducted. RESULTS A total of 22 patients were included. There were 8 males (36.4%) and 14 females (63.6%), aged from 23 to 89 years, with an average age of years. The PPIs involved included omeprazole in 10 cases, esomeprazole in 6 cases, pantoprazole in 3 cases, and lansoprazole in 3 cases. SCARs occurred from 1 to 45 days, with an average time of days after treatment, and 18 cases (94.7%) within 3 weeks. Ten cases were diagnosed as Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), 7 cases were diagnosed as drug reaction with eosinophilia and systemic symptom (DRESS), and 5 cases were diagnosed as acute generalized exanthematous pustulosis (AGEP). The clinical symptoms and laboratory indicators of 18 patients (81.8%) were improved after discontinuation and treatment with glucocorticoid and/or globulin, but three patients died of multiple organ failure eventually, and one patient was discharged automatically. CONCLUSION SCARs can be caused by a variety of PPIs, with omeprazole and esomeprazole being relatively more common, and mainly manifest as SJS/TEN and DRESS. Patients should be closely monitored for any allergic symptoms such as fever and rash within 6 weeks of using PPIs. Once SCARs are suspected, the drug should be stopped in time, and symptomatic supportive treatment such as glucocorticoids should be provided if necessary.

OBJECTIVE To multi-dimensionally analyze the characteristics of adverse drug reaction (ADR) reports of medical institutions at different levels by the method of Pareto anlysis to provide accurate data reference for ADR monitoring and safe drug use in clinic thus to better guarantee public medication safety. METHODS ADR reports of 5 tertiary medical institutions, 7 secondary medical institutions, and 12 primary medical institutions and 7 private medical institutions in a district of Shanghai from 2021 to 2023 were retrospectively collected. The characteristics of ADRs were first explored from the time and the medical institution level dimensions. Then, these collected ADR reports were further analyzed using the method of Pareto diagram analysis to identify the mainly and high-frequencily involved drug categories and organ systems. RESULTS A total of 4 279 ADR reports were collected in this study. General ADRs accounted for 85.91% and chemical drug-induced ADRs accouted for 79.48%. From temporal perspective, the number of ADR reports displayed increasing tendency from 2021 to 2023. The elderly were the most involved age groups of human population. Females were more involved than males. From the perspective of medical institution level, ADR reports of tertiary and secondary medical institutions were much more than primary and private medical institutions. In tertiary and secondary medical institutions, the majority of ADRs were induced by anti-infective drugs, anti-tumor and tumor adjuvant drugs, and medication for mental illnesses. Diseases of skin and its subcutaneous tissues, as well as gastrointestinal system were the most common ADR symptoms. In primary medical units, ADRs were most commonly occurred in elderly people, accounting for 81.58%. The majority of ADRs were induced by traditional Chinese medicine (TCM)preparations and cardiovascular drugs, accounting for 29.26% and 23.07%, respectively. Diseases of gastrointestinal symptoms accounted for 34.21% which were the most common ADR symptoms. CONCLUSION Based on the criteria of Pareto classification, there are significant differences in the main drug categories causing ADRs in different levels of medical institutions, but no significant differences were found in the ADR-involved organ systems. Pareto analysis is a reliable menthod to identify drug categories and ADR symptoms needing intensive monitoring. It would facilitate precise adverse reaction monitoring and enhance clinical medication safety.