Background: Chronic diabetic peripheral neuropathic pain (DPNP) is common and difficult to treat. The recommended medications are either inadequate effective or limited by the side effects. This study aims to evaluate the efficacy and safety of HSK16149, a potent, selective ligand of the a2δ subunit of voltage-gated calcium channels (VGCC), as analgesia treatment for DPNP. Materials and Methods: This was a randomized, double-blind, placebo and active-controlled phase II/III study of patients aged ≥18 years with diabetic peripheral neuropathy in China. Firstly, the patients with moderate to severe pain were randomized to receive placebo, HSK 16149 40,80 mg/d without titration, and HSK16149 120, 160mg/d, pregabalin 300mg/d with 1 week titration on average. Then more patients were recruited and randomized to placebo and two HSK16149 dose groups, continued the treatment for up to 13 weeks. The primary endpoint was the change from baseline in average daily pain score (ADPS) at week 13. The secondary endpoint was the responder rates as ≥30% and ≥50% improvement in ADPS. Results: Compared with placebo, the pain was reduced since week 1 in HSK16149 groups. At week 13, the mean ADPS change from baseline was -1.23, -2.24 and -2.16 for placebo (n=177), HSK 16149 40mg/d (n=178) and 80mg/d (n=179), showing statistical significance for both HSK groups versus placebo (P<0.0001). The 30% and 50% responder rate were both significantly greater for two HSK groups versus placebo (≥30%: 57.3%, 51.4% versus 31.6%; ≥50%: 32.0%, 36.3% versus 18.1%) at week 13. Most treatment-emergent adverse events (TEAE) in HSK16149 groups were mild to moderate, and the most frequent TEAEs were dizziness and somnolence, which were always transient and needed no additional treatment. Conclusions: HSK 16149 rapidly improved analgesia without titration and was efficacious in relieving pain in Chinese DPNP patients, and well tolerated. Disclosure X.Guo: None. T.Zhang: None. G.Yuan: None. L.Yukun: None. J.Ma: None. L.Hong-mei: None.

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After a large-scale radiological accident, such as Chernobyl or Fukushima Nuclear Power Plant accident occurred, rapid and high-throughput biodosimetry would be needed. It is very important to find a rapid, high-throughput biodosimeter for massive population triage and biological dose estimation. Studies showed that Circular RNA (circRNA) expressions can be altered by ionizing radiation in normal human cell lines and tumor tissue. Whether circRNAs are suitable for triage and dose estimation remains unclear. In this study, radiation-induced differential expressed circRNAs were screened through transcriptome sequencing with human lymphoblastoid cell line AHH-1 at 4 h after irradiated with 0, 2, and 5 Gy Cobalt-60 γ-rays. The results showed that 3 up-regulated and 4 down-regulated circRNAs were identified in 2 Gy-induced cells, and 5 up-regulated and 3 down-regulated circRNAs were identified in 5 Gy-induced cells both compared with those in the 0 Gy group. After validation, 11 circRNAs were chosen for establishing the expression dosimetry models, because their expression levels changed in a dose-dependent manner. Different circRNA expression models involving one or two circRNAs were established by stepwise regression analysis for different time-point (4h, 12 h, 24 h, and 48 h) post-irradiation, with R2 ranged from 0.950 to 0.998 (P < 0.01). A blind test showed that most of the estimated doses based on the expression models were deviated from the actual absorbed doses and the relative deviation were higher than 20%. In conclusion, ionizing radiation can alter the circRNA expression profile in the normal cell line AHH-1. Some circRNAs may be having the potential for being radiation biomarkers and needs further comprehensive investigation.