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), ß-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.

Synthesis of 2-Amino-5-acylthiazoles by a Tertiary Amine-Promoted One-Pot Three-Component Cascade Cyclization Using Elemental Sulfur as a Sulfur Source.

A novel one-pot three-component cascade cyclization strategy for the synthesis of 2-amino-5-acylthiazoles using enaminones, cyanamide, and elemental sulfur has been developed. The reported methods have demonstrated good tolerance of various functional groups. Up to 28 2-amino-5-acylthiazole compounds bearing diverse structural differences were successfully synthesized from easily obtained starting materials with moderate to excellent yields. Our method provides an effective way for the access of valuable and potentially bioactive 2-amino-5-acylthiazole derivatives.

Dysregulation of microRNA­23b­3p contributes to the development of intracranial aneurysms by targeting phosphatase and tensin homolog.

MicroRNA­23b­3p (miR­23b­3p) has been reported to be involved in the pathogenesis of a number of diseases, including non­small cell lung cancer and gastric cancer, by acting on different signaling pathways. The present study aimed to understand the association between the miR­23b­3p level of intracranial aneurysms (IAs) and the mechanism involved. Computational analysis was used to search for the target of miR­23b­3p, and luciferase assay was used to validate the miRNA/target association. Western blot analysis and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to determine the expression of miR­23b­3p and phosphatase and tensin homolog (PTEN), and their expression in smooth muscle cells (SMCs) treated with miRNA mimic or inhibitor. Firstly, an online miRNA database (www.mirdb.org) was searched using the 'seed sequence' located within the 3'­untranslated region of the target gene, and then PTEN was validated as the direct target gene via a luciferase reporter assay system. The negative regulatory association between miR­23b­3p and PTEN was determined through the analysis of the relative luciferase activity. Additionally, RT-qPCR and western blot analysis was performed in order to assess the mRNA and protein expression levels of PTEN among IA (n=32) and control (n=17) groups or cells treated with scramble control, miR­23b­3p mimics, PTEN siRNA and miR­23b­3p inhibitors to verify the negative regulatory association between miR­23b­3p and PTEN. Experiments were then performed to investigate the effect of miR­23b­3p and PTEN on the viability and apoptosis of pulmonary artery SMCs (PASMCs). The results showed that cells transfected with miR­23b­3p inhibitors suppressed the viability of SMCs by promoting the apoptosis of the cells compared with that of the scramble controls, while cells transfected with miR­23b­3p mimics and PTEN siRNA enhanced the viability of VSMCs by inducing apoptosis. This indicated that miR­23b­3p negatively interfered with the viability of the cells, while PTEN positively interfered with the viability of the cells. In conclusion, PTEN was found to be a virtual target of miR­23b­3p, and a negative regulatory association existed between miR­23b­3p and PTEN. miR­23b­3p and PTEN interfered with the viability and apoptosis of SMCs.

Benefits of hyperbaric oxygen pretreatment for decompression sickness in Bama pigs.

Decompression sickness (DCS) occurs when ambient pressure is severely reduced during diving and aviation. Hyperbaric oxygen (HBO) pretreatment has been shown to exert beneficial effects on DCS in rats via heat-shock proteins (HSPs). We hypothesized that HBO pretreatment will also reduce DCS via HSPs in swine models. In the first part of our investigation, six swine were subjected to a session of HBO treatment. HSP32, 60, 70 and 90 were detected, before and at 6, 12, 18, 24 and 30 h following exposure in lymphocytes. In the second part of our investigation, another 10 swine were randomly assigned into two groups (five per group). All swine were subjected to two simulated air dives in a hyperbaric chamber with an interval of 7 days. Eighteen hours before each dive, the swine were pretreated with HBO or air: the first group received air pretreatment prior to the first dive and HBO pretreatment prior to the second; the second group were pretreated with HBO first and then air. Bubble loads, skin lesions, inflammation and endothelial markers were detected after each dive. In lymphocytes, all HSPs increased significantly (P<0.05), with the greatest expression appearing at 18 h for HSP32 and 70. HBO pretreatment significantly reduced all the determined changes compared with air pretreatment. The results demonstrate that a single exposure to HBO 18 h prior to diving effectively protects against DCS in the swine model, possibly via induction of HSPs.

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 siRNA 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 siRNA, 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 siRNA 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.

[A non-familial May-Hegglin anomaly accompanying with MYH9 gene R1933X mutation and I1626V polymorphism].

OBJECTIVES: To identify the nonmuscle myosin heavy chain 9 (MYH9) gene mutation site in a May-Hegglin anomaly(MHA) patient, and to analyze the genotype of her relatives to exclude the inherit correlation between the proband and her family members. METHODS: Inclusion bodies in neutrophils of the proband were examined by transmission electron microscope, and giant platelets by scanning electron microscope. The mutation "hot spot" on the MYH9 gene of the proband and her family members was amplified with polymerase chain reaction(PCR), and then sequenced in both directions to identify the mutant site. RESULTS: (1) The proband manifested with the typical MHA triad of giant platelet, thrombocytopenia and Dohle-like inclusion bodies in neutrophil. However, all of the proband's family members had no such anomaly. (2) Transmission electron microscope and scanning electron microscope confirmed that giant platelets and neutrophils inclusion bodies existed in the proband peripheral blood cells. (3) There was a missense mutation 5797 C-->T in the exon 40 of MYH9 gene which led to Arg changing into termination codon (Arg1933 stop). The proband also had a heterozygous mutation 4876A-->G in exon 33. There was no abnormal finding in the sites mentioned above in her mother, while her father carried the homozygous 4876A-->G mutation. CONCLUSIONS: This MHA case is a sporadic one, in whose family a mode for autosomal dominant inheritance can not be established. The 5797C-->T substitution in MYH9 gene is a pathogenic mutation, however, 4876A-->G is simply a polymorphism.