Ecological risk assessment of heavy metals in tea plantation soil around Tai Lake region in Suzhou, China.

Tea plant [Camellia sinensis (L.) O. Kuntze] is one of the important foliar cash crops in China, and its root system absorbs heavy metal (HM) elements enriched in the soil and transports them to the over ground part. In order to ensure the safety of the soil ecological environment and tea raw materials in the tea production area, the HM contents of soil and tea plant leaves in Suzhou tea plantations were detected, the relationship between HMs and soil physicochemical properties was analyzed, and the ecological risk of HMs in tea plantation soils was evaluated by using relevant detection techniques and evaluation models. The results showed that the average pH of tea plantation soils around Tai Lake in Suzhou was within the range suitable for the growth of tea plants. The pH, soil organic matter, total nitrogen, available phosphorus and available potassium of tea plantation soil satisfying the requirements of high quality, high efficiency and high yield ('3H') tea plantation accounted for 47.06%, 26.47%, 8.82%, 79.41% and 67.65%, respectively. Site 2 fully met the requirements of '3H' tea plantation. In addition, the contents of cadmium (Cd) and mercury (Hg) were extremely variable, and the average contents exceeded the background value of soil in Jiangsu Province, but the HM contents of tea leaves all met the pollution-free standard, and the HM contents of tea leaves around Tai Lake in Suzhou were generally at a safe level. The composite ecological risk index ranged from 0.05 to 0.60, and 32 of the 34 sample sites (except site 21 and site 23) are the most suitable agricultural land for tea plantations.

Patient-derived melanoma organoid models facilitate the assessment of immunotherapies.

BACKGROUND: Only a minority of melanoma patients experience durable responses to immunotherapies due to inter- and intra-tumoral heterogeneity in melanoma. As a result, there is a pressing need for suitable preclinical models to investigate resistance mechanisms and enhance treatment efficacy. METHODS: Here, we report two different methods for generating melanoma patient-derived organoids (MPDOs), one is embedded in collagen gel, and the other is inlaid in Matrigel. MPDOs in Matrigel are used for assessing the therapeutic effects of anti-PD-1 antibodies (αPD-1), autochthonous tumor infiltrating lymphocytes (TILs), and small molecule compounds. MPDOs in collagen gel are used for evaluating the chemotaxis and migratory capacity of TILs. FINDING: The MPDOs in collagen gel and Matrigel have similar morphology and immune cell composition to their parental melanoma tissues. MPDOs show inter- and intra-tumoral heterogeneity and contain diverse immune cells such as CD4+, CD8+ T, Treg, CD14+ monocytic, CD15+, and CD11b+ myeloid cells. The tumor microenvironment (TME) in MPDOs is highly immunosuppressive, and the lymphoid and myeloid lineages express similar levels of PD-1, PD-L1, and CTLA-4 as their parental melanoma tissues. Anti-PD-1 antibodies (αPD-1) reinvigorate CD8+ T cells and induce melanoma cell death in the MPDOs. TILs expanded by IL-2 and αPD-1 show significantly lower expression of TIM-3, better migratory capacity and infiltration of autochthonous MPDOs, and more effective killing of melanoma cells than TILs expanded by IL-2 alone or IL-2 with αCD3. A small molecule screen discovers that Navitoclax increases the cytotoxicity of TIL therapy. INTERPRETATION: MPDOs may be used to test immune checkpoint inhibitors and cellular and targeted therapies. FUNDING: This work was supported by the NIH grants CA114046, CA261608, CA258113, and the Tara Miller Melanoma Foundation.

Case Report: Predicting the Range of Lamotrigine Concentration Using Pharmacokinetic Models Based on Monte Carlo Simulation: A Case Study of Antiepileptic Drug-Related Leukopenia.

Lamotrigine (LTG), a wide-spectrum antiepileptic drug, is frequently associated with cutaneous side-effects, whereas hematological side-effects such as leukopenia have rarely been reported for it. We report the case of a 15-year-old Chinese female epileptic patient weighing 60 kg who developed combined asymptomatic leukopenia after receiving concomitant therapy with LTG and valproate acid (VPA). In this case report, antiepileptic drug-related leukopenia may have occurred in definite relation to an increase in LTG concentration and reversed with the discontinuation of VPA. Monte Carlo (MC) simulations were performed to estimate the steady-state serum concentrations (C ss ) of LTG for different dosing regimens in adolescent Chinese epileptic patients weighing the same as the patient considered in the case study, based on pharmacokinetic (PK) models published in past research. Adjustments to the dosage of LTG for the patient were analyzed to illustrate the application of MC simulations and verify the results. The predicted LTG concentrations within a prediction interval between the 10th and 90th percentiles that represented 80% of the simulated populations, could adequately capture the measured LTG concentrations of the patient, indicating that MC simulations are a useful tool for estimating drug concentrations. Clinicians may benefit from the timely probabilistic predictions of the range of drug concentration based on an MC simulation that considers a large sample of virtual patients. The case considered here highlights the importance of therapeutic drug monitoring (TDM) and implementing model-informed precision dosing in the course of a patient's individualized treatment to minimize adverse reactions.