Danggui Buxue Tang (DBT) is a simple decoction, having about 800 years of usage in China to treat menopausal irregularity in women, which contains two herbs: Radix Astragali (Huangqi) and Radix Angelicae Sinensis (Danggui). Traditionally, boiling water has been used for preparing DBT; however, the optimized conditions of extraction have not yet been determined. Here, the amounts of Radix Astragali-derived astragaloside IV, calycosin, formononetin, and Radix Angelicae Sinensis-derived ferulic acid and ligustilide were determined in DBT, which were extracted according to an orthogonal array experimental design having three variable parameters: extraction time, extraction volume and number of repeats of the extraction. Our results suggest that extraction time and number of repeats of the extraction are two crucial factors, while extraction volume is a subordinate factor. The optimized conditions for extraction were therefore established. Besides the chemical composition, the estrogenic and anti-platelet aggregation activities of DBT were determined in different groups of the extraction, and the results of bioassays were in line with the amounts of the analyzed chemical ingredients. The results provide a model system for establishing the quality assurance of the herbal preparation.

Recently, chimeric antigen receptor (CAR)-T cell therapy has shown great promise in treating haematological malignancies1–7. However, CAR-T cell therapy currently has several limitations8–12. Here we successfully developed a two-in-one approach to generate non-viral, gene-specific targeted CAR-T cells through CRISPR–Cas9. Using the optimized protocol, we demonstrated feasibility in a preclinical study by inserting an anti-CD19 CAR cassette into the AAVS1 safe-harbour locus. Furthermore, an innovative type of anti-CD19 CAR-T cell with PD1 integration was developed and showed superior ability to eradicate tumour cells in xenograft models. In adoptive therapy for relapsed/refractory aggressive B cell non-Hodgkin lymphoma (ClinicalTrials.gov, NCT04213469), we observed a high rate (87.5%) of complete remission and durable responses without serious adverse events in eight patients. Notably, these enhanced CAR-T cells were effective even at a low infusion dose and with a low percentage of CAR+ cells. Single-cell analysis showed that the electroporation method resulted in a high percentage of memory T cells in infusion products, and PD1 interference enhanced anti-tumour immune functions, further validating the advantages of non-viral, PD1-integrated CAR-T cells. Collectively, our results demonstrate the high safety and efficacy of non-viral, gene-specific integrated CAR-T cells, thus providing an innovative technology for CAR-T cell therapy.

A novel multifunctional Ag S quantum dot (QD)-based nanomedicine of alendronate (Ald)/doxorubicin (DOX)@Ag S is developed for highly effective bone tumor therapy in an orthotopic model. The bone-targeting and osteolysis inhibition of Ald and the chemotherapeutic effect of DOX on the bone tumor are in situ visualized by Ag S QDs with emission in the second near-infrared window.

CD19-targeting chimeric antigen receptor (CAR)-T cell therapy has shown great efficacy in patients with relapsed/ refractory non-Hodgkin lymphoma (NHL) but has been associated with serious adverse effects, such as cytokine release syndrome (CRS). It has been speculated that NHL baseline disease burden might affect clinical outcome and CRS, but this has not been explored in detail in any previous study. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG), as measured by fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET-CT), are quantitative indicators of baseline tumor burden. Using FDG PET-CT, we calculated baseline and post-CAR-T cell therapy MTV and TLG in 19 patients with NHL. The median MTV was 72 cm 3 (range, .02 to 1137.7 cm 3 ), and the median TLG was 555.9 (range, .011 to 8990.3). After a median follow-up of 5 months (range, 1 to 12 months), the best overall response rate was 79.0%. The baseline MTV and TLG did not differ significantly between patients with response and those without response (P = .62 and .95, respectively). On Cox regression analysis, baseline MTV and TLG were not significantly associated with overall survival (P = .67 and .45, respectively). Patients with mild and moderate CRS (grade 0 to 2) had significantly lower MTV and TLG than those with severe CRS (grade 3 to 4) (P = .008 for MTV comparison, P = .011 for TLG comparison). Using FDG PET-CT, we also demonstrated that CAR-T cell therapy in patients with NHL was associated with pseudoprogression and local immune activation. Our data indicate that patients with higher baseline disease burden have more severe CRS, and that CAR-T cell therapy is associated with lymphoma pseudoprogression and local immune activation.

FDG-PET is especially effective in detecting patients with elevated thyroglobulin levels and normal radioiodine WBS; FDG-PET/CT is a more sensitive method in the follow-up of thyroid cancer recurrence or metastases, particularly in those with negative WBS.