Safety profile of 0.0015%tafluprost eye drops in China:a post-marketing observational study

AIM:To investigate the treatment pattern and safety of tafluprost for glaucoma and ocular hypertension(OH)in clinical practice in China.METHODS:This post-marketing observational study included patients who received tafluprost to lower intraocular pressure(IOP)within 30d between September 2017 and March 2020 in 20 hospitals in China.Adverse drug reactions(ADRs)during tafluprost treatment and within 30d after the treatment were collected.RESULTS:A total of 2544 patients were included in this study,of them 58.5%(1488/2544)had primary open angle glaucoma(POAG),21.9%(556/2544)had OH and 19.7%(500/2544)used tafluprost for other reasons.Of 359 ADRs occurred in 10.1%(258/2544)patients,and no serious adverse event occurred.The most common ADR was conjunctival hyperemia(128 ADRs in 124 patients,4.9%).Totally 1670 participants(65.6%)combined tafluprost with carbonic anhydrase inhibitors(CAIs;37.1%,620/1670),sympathomimetics(33.5%,559/1670),β-blockers(33.2%,555/1670),other prostaglandin analogs(PGAs;15.6%,260/1670)and other eye drops(15.1%,253/1670).The highest incidence of conjunctival hyperemia was noted in patients who received tafluprost in combination with other PGAs(23 ADRs in 23 patients,8.8%,23/260)and the lowest was in combination with CAIs(16 ADRs in 16 patients,2.6%,16/620).Tafluprost was applied in primary angle-closure glaucoma(41.6%,208/500),after glaucoma surgery(17.8%,89/500)and after non-glaucoma surgery(15.8%,79/500).CONCLUSION:Tafluprost is safe for POAG and OH,and tolerable when combined with other eye drops and under various clinical circumstances.

Study on the role of Cathepsin B and JNK signaling pathway in the development of cerebral aneurysm

Objective: To investigate the correlation between JNK signal and the apoptosis of VSMC as well as the expression of Cathepsin B and to explore the role of JNK signal in the development of cerebral aneurysm. Methods: Rat models of cerebral aneurysm were established and histopathologic changes of cerebral aneurysm and the apoptosis of VSMC were analyzed. Rat models were respectively subject to subcutaneous injection of Cathepsin B si RNA and JNK inhibitor SP600125. Western blot technique was used to detect the expression of proteins like Cathepsin B, Caspase-3, and p-JNK. Spearman's rho was used to examine the correlation between p-JNK and Cathepsin B, as well as the expression of relevant proteins. Results:The success rate of modeling rats with cerebral aneurysm was 88.75%. After the respective injection of Cathepsin B si RNA, SP600125 and their combination, the cell densities of VSMC of rats with cerebral aneurysm all increased significantly(P<0.05 or P<0.01), but the apoptosis rate of VSMC decreased significantly(P<0.01). Compared with normal rats, the expression of Cathepsin B, Caspase-3 and p-JNK in cerebral aneurysm models increased significantly. Effectively intervening Cathepsin B genes with Cathepsin B si RNA could significantly inhibit the expression of Cathepsin B and Caspase-3, but hardly influence the expression of p-JNK. JNK inhibitor SP600125 had no influence on the expression of Cathepsin B and Caspase-3, but effectively inhibited the expression of p-JNK. In cerebral aneurysm tissues, positive correlation was observed between the expression of p-JNK and Cathepsin B, the correlation coefficient was r=0.640. Conclusion: After the attack of cerebral aneurysm, proteins like Cathepsin B, Caspase-3 and p-JNK are all involved in the apoptosis of VSMCs. This process may be realized by Cathepsin B which activates the apoptosis mechanism of Caspase-3 and mediate the apoptosis of VSMC through the JNK signaling pathway. Therefore, silencing Cathepsin B gene or inhibiting the conduction through JNK signaling pathway can mitigate the apoptosis of vascular smooth muscle cells in cerebral aneurysm.