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Tislelizumab may induce immune-related adverse events, especially adverse skin events. Early detection and timely intervention of cutaneous adverse events are crucial to improve patients' quality of life and reduce the disruption of therapeutic regimens. This study aimed to determine the clinical characteristics of cutaneous adverse reactions to tislelizumab and offer a reference for its rational clinical use. Case reports of cutaneous adverse reactions induced by tislelizumab were collected from the relevant databases (up to 31 March 2023). Patient age, sex, primary disease, medication use, occurrence of adverse skin conditions, treatment, and outcomes were recorded and descriptively analysed. A total of 13 patients were enrolled, including six males and seven females, aged 55–79 years, with a median age of 75 years and a mean age of 70.92 ± 8.84 years. The original disease was lung carcinoma in none patients, cervical carcinoma in two, and urothelial carcinoma and squamous cell carcinoma in one each. The time from the initiation of medication use to the occurrence of cutaneous adverse reactions ranged from 7 to 177 days. Among the 13 patients, 10 showed improvement after drug withdrawal or symptomatic treatment. Two patients died (one died of disease progression and multiorgan failure, one died of acute coronary syndrome), and one patient's adverse skin reactions persisted without treatment. Tislelizumab-related cutaneous adverse reactions mostly occur after several days to months of treatment. In clinical practice, evaluation and monitoring should be strengthened. More attention should be paid to erythema and rashes, which may be signs of serious adverse skin reactions. Early detection and intervention can ensure the safe use of drugs and provide greater clinical benefits to patients. [ABSTRACT FROM AUTHOR]

To explore the association between polymorphisms in microRNAs (miRNAs) and the cholinesterase (ChE) activity in omethoate-exposed workers, we recruited 180 omethoate-exposed workers and 115 controls to measure their ChE activity using acetylcholine and dithio-bis-(nitrobenzoic acid) and genotype susceptible SNPs in their miRNA by time-of-flight mass spectrometry. ChE activity in the exposure group was lower than that in the control group (P < 0.001). The analysis of covariance result showed that ChE activity was lower in the (- -/- T) genotype in miR-30a rs111456995 (1.97 ± 0.47) than in the TT genotype (2.23 ± 0.59) of the exposure group (P = 0.004). Multivariate linear regression was performed to find influencing factors on ChE activity, and variables kept in the model included omethoate exposure (b = −1.094, P < 0.001), gender (b = −0.381, P < 0.001), miR-30a rs111456995 (- -/- T)(b = −0.248, P < 0.001), and drinking (b = 0.258, P =0.019). The results suggest that individuals carrying a (- -/- T) genotype in miR-30a rs111456995 were more susceptible to damage in their cholinesterase induced by omethoate exposure. [ABSTRACT FROM AUTHOR]

Context:Caffeic acid phenethyl ester (CAPE), isolated from honeybee propolis, has pharmacological applications. A synthesized CAPE derivative,p-nitro-caffeic acid phenethyl ester (CAPE-NO2), showed similar activities with CAPE. The pharmacological activities of CAPE and CAPE-NO2are related to their absorption properties. Objective:To understand the pharmacokinetic profiles of CAPE and CAPE-NO2in rats and investigate the absorption mechanisms and effects on P-glycoprotein in Caco-2 cells. Materials and methods:The pharmacokinetic profiles of CAPE and CAPE-NO2were obtained after oral administration (10 mg/kg) to rats. Transport studies of CAPE and CAPE-NO2(5, 10, 20 μM) were performed in Caco-2 cell model. P-gp activities were assayed by rhodamine 123 cellular retention. Expression of P-gp was determined after the cells were administrated with CAPE and CAPE-NO2(5, 20 μM) for 48 and 72 h. Results:The AUC(0−t)of CAPE-NO2(3239.9 ± 352 ng × h/mL) was two-time greater than CAPE (1659.6 ± 152 ng × h/mL) in rats. ThePappvalues of CAPE and CAPE-NO2were (4.86 ± 0.90) × 10−6 cm/s and (12.34 ± 1.6) × 10−6 cm/s, respectively. The accumulation of rhodamine 123 was increased by 1.3- to 1.9-fold and 1.4- to 2.3-fold in CAPE and CAPE-NO2groups after 1 h administration, respectively. However, CAPE and CAPE-NO2increased the P-gp levels by 2.1- and 1.7-fold, respectively. Conclusion:The absorption of CAPE-NO2can be enhanced in rats and Caco-2 cells compared with CAPE. The two compounds are potential inhibitors of P-gp. The increased P-gp levels generated by CAPE and CAPE-NO2played a role as a defense mechanism by limiting intracellular xenobiotic levels. [ABSTRACT FROM AUTHOR]

The medical properties of baicalin have been well known for many years. However, the discovery that baicalin in the presence of metal ions is more effective than baicalin alone changed the course of drug research. The present study was designed to investigate the effect and possible mechanism of apoptosis induced by baicalin-copper in a human hepatoblastoma cancer cell line (HepG2) and in vivo. This study demonstrated that baicalin-copper suppresses the proliferation of HepG2 cells in a dose-dependent manner. Intraperitoneal injection of baicalin-copper resulted in a significant decrease in tumor growth in xenografts in nude mice. Acridine orange staining and flow cytometry analysis demonstrated that baicalin-copper induced apoptosis in HepG2 cells and caused cells to arrest in G2-M phase of the cell cycle. Furthermore, baicalin-copper treatment significantly increased the Bax/Bcl-2 ratio and p38 levels, as well as decreased the expression of caspase-3, p-PI3K, p-Akt and p-mTOR ( P < 0.01). All of the evidences above indicate that baicalin-copper induces apoptosis in HepG2 cells by down-regulating the PI3K/Akt/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]