Paediatric off-label use of drugs in Gansu, China: a multicentre cross-sectional study.

OBJECTIVE: To examine the current prevalence and cost of paediatric off-label drug prescriptions in Gansu, China, and the potential influencing factors. DESIGN: The prevalence of off-label prescriptions in paediatrics was evaluated according to the National Medical Products Administration drug instructions in the China Pharmaceutical Reference (China Pharmaceutical Reference, MCDEX) database. The evidence of the prescription was determined by existing clinical practice guidelines and the Thomson Grade in the Micromedex 2021 compendium. We used logistic regression to investigate the characteristics that influence paediatric off-label drug use after single-factor regression analysis. SETTING: A multicentre cross-sectional study of outpatient paediatric prescriptions in 196 secondary and tertiary hospitals in Gansu Province, China, in March and September 2020. RESULTS: We retrieved 104 029 paediatric prescriptions, of which 39 480 (38.0%) contained off-label use. The most common diseases treated by off-label drugs were respiratory system diseases (n=15 831, 40.1%). A quarter of off-label prescriptions had adequate evidence basis (n=10 130, 25.6%). Unapproved indications were the most common type of off-label drug use (n=25 891, 65.6%). A total of 1177 different drugs were prescribed off-label, with multienzyme tablets being the most common drug (n=1790, 3.5%). The total cost of the prescribed off-label drugs was ¥106 116/day. Off-label prescriptions were less frequent in tertiary than in secondary hospitals. Topical preparations were more commonly prescribed off-label than other types of drugs. Senior-level clinicians prescribed drugs off-label more often than intermediate and junior clinicians. CONCLUSION: Off-label drug use is widespread in paediatric practice in China. Three-quarters of the prescriptions may potentially include inappropriate medication use, resulting in a daily economic burden of about ¥81 000 in 2020 in Gansu Province with 25 million inhabitants. The management of off-label drug use in paediatrics in China needs improvement.

Neuronostatin promotes soluble Aß1-42 oligomers -induced spatial learning and memory impairments in mice.

Neuronostatin (NST) is composed of a 13-amino acid and amidated peptide hormone encoded in the somatostatin (SST) gene, and plays an important physiological function in diverse tissues. Previous studies have shown that intracerebroventricular (i.c.v.) and intra-hippocampally administration of NST can significantly decrease the percentage of novel object exploration time in the step-down test. In this study, to define the contribution of NST to cognitive impairments induced by soluble Aß42 oligomers (oAß), along with the underlying mechanisms. This study used behavioral, biochemical and immunohistological methods to find that i.c.v. administration of NST (3 nmol/mouse) disrupted the ability of spatial learning and memory in mice, led to increase the levels of cAMP, GPR107 protein expression and phosphorylation of PKA at Thr197 in the cortex and hippocampus. NST promoted oAß (1 nmol/mouse) -induced cognitive impairments, subsequently co-injection of NST and oAß increased the levels of GPR107 expression and PKA phosphorylation, which also led to hyperactivation of GFAP in the cortex and neuroinflammation cytokines (IL-1ß, IL-6 and TNFα) both in the cortex and hippocampus. Moreover, it was demonstrated that co-administration of NST and oAß had increased the phosphorylation of Akt and GSK3ß and reduced the levels of ATP and hexokinase (HK) activity in the cortex. Therefore, taken together, this study provided powerful insight into the mechanism of NST for memory impairments induced by oAß, and may potentially serve as a promising target for future Alzheimer's disease interventions.

Neuronostatin ameliorates sodium taurocholate-induced acute pancreatitis in rats.

BACKGROUND AND AIMS: Neuronostatin is encoded in the preprosomatostatin gene and exerts important physiological actions on neuronal and cardiovascular regulation and metabolism in diverse tissues. An intraperitoneal injection of neuronostatin can induce c-Jun expression in the periphery of pancreatic islets. Because of the relatively high amount of neuronostatin present in the pancreas, it is necessary to investigate the effects of neuronostatin on pancreas. Furthermore, little is known about the effect of neuronostatin on acute pancreatitis. METHODS: Neuronostatin (30, 60, and 120 nmol) was injected in to the external jugular vein 30 min before retrograde infusion of 2 % sodium taurocholate into the pancreaticobiliary duct. After 6 h, histological damage of the pancreas was evaluated by pancreas weight and paraffin section. A blood sample was collected to determine the serum amylase and lipase activities. RESULTS: In our findings, neuronostatin groups had a reduction in interstitial edema, acinar cell vacuolization, and inflammatory infiltration of the pancreas compared with the model group. Biochemical data showed that serum amylase and lipase activities were significantly decreased in neuronostatin-pretreated groups by comparison with the model group. CONCLUSIONS: Histopathologic examination suggests that neuronostatin ameliorated the histological damage of sodium taurocholate-induced acute pancreatitis in rats. The biochemical analysis was consistent with that obtained from histopathologic examination, which was toward a trend of attenuating acute pancreatitis. In summary, neuronostatin might be potentially capable of ameliorating pancreatic damage in acute pancreatitis in rats.

Synergistic analgesic effects between neuronostatin and morphine at the supraspinal level.

Neuronostatin, a 13-amino acid peptide, is encoded in the somatostatin pro-hormone. I.c.v. administration of neuronostatin produces a significant antinociceptive effect in the mouse tail-flick test, which is mediated by endogenous opioid receptor. However, the direct functional interaction between morphine and neuronostatin has not been characterized. In the present study, effect of neuronostatin on morphine analgesia was investigated in the tail-flick test. Our findings showed that i.c.v. administration of neuronostatin (0.3nmol/mouse i.c.v.) significantly enhanced the antinociceptive effect of morphine (2.5, 5 or 10µg/kg) at the supraspinal level. Results of antagonism experiments suggested that the synergistic analgesia induced by morphine and neuronostatin was mediated by µ- and к-opioid receptors not δ-opioid receptor. In conclusion, there may be a cascade amplification phenomenon when morphine and neuronostatin were co-administered in acute pain model. The above results provide evidence for the potential use of neuronostatin in combination with morphine to control pain and addiction.