Lidocaine has been reported to induce apoptosis on rabbit corneal endothelial cells. However, the apoptotic effect and exact mechanism involved in cytotoxicity of lidocaine are not well‐established in human corneal endothelial (HCE) cells. In this study, we investigated the apoptosis‐inducing effect of lidocaine on HCE cells in vitro. After HCE cells were treated with lidocaine at concentrations of 0.15625–10.0 g/l, the morphology and ultrastructure of the cells were observed by inverted light microscope and transmission electron microscope (TEM). Cell viability was measured by MTT assay, and the apoptotic ratio was evaluated with flow cytometry and fluorescent microscopic counting after FITC–Annexin V/PI and AO/EB staining. DNA fragmentation was detected by electrophoresis, and the activation of caspases was evaluated by ELISA. In addition, changes in mitochondrial membrane potential were determined by JC‐1 staining. Results suggest that lidocaine above 1.25 g/l reduced cellular viability and triggered apoptosis in HCE cells in a time‐ and dose‐dependent manner. Diminishment of ΔΨm and the activation of caspases indicate that lidocaine‐induced apoptosis was caspase dependent and may be related to mitochondrial pathway.

Objectives: To determine the differences in a proliferation-inducing ligand (APRIL) between seropositive and seronegative rheumatoid arthritis (RA) patients and further investigate the possible pathogenesis of the two subtypes of RA. Method:Concentrations of APRIL in sera (18 seropositive RA patients, 16 seronegative RA patients, and 10 healthy controls) and synovial fluid (SF) (eight seropositive RA patients, two seronegative RA patients, and 10 controls) were detected by enzyme-linked immunosorbent assay (ELISA). Infiltration of plasma cells, macrophages, and APRIL-positive cells in the synovium [14 seropositives, eight seronegatives, and 10 osteoarthritis (OA) controls] was detected by immunohistochemistry. Correlations between serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), 28-joint Disease Activity Score (DAS28), and sera/SF levels of APRIL and synovial cell infiltration were analysed. Results: The mean serum APRIL level of seropositive RA patients was significantly higher than that of seronegative patients (26.1 ± 31.2 vs. 8.0 ± 10.2 ng/mL, p = 0.03). The level of APRIL in the SF of seropositive RA patients was comparable to that of seronegative patients [47.9 ± 54.4 vs. 32.82 (6.52–59.12) ng/mL, p > 0.05]. The SF APRIL level of RA patients was higher than that of patients with other inflammatory arthritis. Dramatically increased infiltration of APRIL-positive cells in the RA synovium was observed compared with the OA group (seropositive RA vs. OA, p < 0.001; seronegative RA vs. OA, p = 0.001). The infiltration of both plasma cells and macrophages was more in seropositive RA than in OA (p = 0.013 and p = 0.003, respectively). Conclusions: The serum APRIL levels of seropositive RA patients are significantly higher than those of seronegative RA patients. APRIL may participate in the formation of seropositive RA.