Evidence mapping and overview of systematic reviews of the effects of acupuncture therapies.

OBJECTIVE: To provide a route map regarding systematic reviews (SRs) of acupuncture therapies that will meet two goals: (1) to identify areas in which more or better evidence is required and (2) to identify acupuncture applications that, although proven effective, remain underused in practice, and thus warrant more effective knowledge dissemination. ELIGIBILITY CRITERIA: We included SRs that conducted meta-analyses (MAs) of randomised controlled trials (RCTs) for this overview. INFORMATION SOURCES: We searched for SRs without language restrictions from January 2015 to November 2020 in four Chinese electronic databases and Epistemonikos database. And we also searched for newly published RCTs that were eligible for selected best SRs in PubMed, Medline, Cochrane Central Register of Controlled Trials, Embase and four Chinese electronic databases from its lasted search dates to November 2020. SYNTHESIS OF RESULTS: We reanalysed the selected MAs if new primary studies were added. We used random-effect model to calculate the overall effect. RESULTS: Our search identified 120 SRs published in the last 5 years addressing acupuncture therapies across 12 therapeutic areas and 77 diseases and conditions. The SRs included 205 outcomes and involved 138 995 participants from 1402 RCTs. We constructed 77 evidence matrices, including 120 SRs and their included RCTs in the Epistemonikos database. Seventy-seven SRs represented the effect estimate of acupuncture therapies. Finally, we system summarised the areas of possible underutilisation of acupuncture therapies (high or moderate certainty evidence of large or moderate effects), and the areas of warranting additional investigation of acupuncture therapies (low or very low certainty evidence of moderate or large effects). CONCLUSION: The evidence maps and overview of SRs on acupuncture therapies identified both therapies with substantial benefits that may require more assertive evidence dissemination and promising acupuncture therapies that require further investigation.

Differential effects of relaxin-3 and a selective relaxin-3 receptor agonist on food and water intake and hypothalamic neuronal activity in rats.

The neuropeptide relaxin-3 (RLN3) binds with high affinity to its cognate receptor, relaxin-family peptide receptor 3 (RXFP3), and with lower affinity to RXFP1, the cognate receptor for relaxin. Intracerebroventricular (icv) administration of RLN3 in rats strongly increases food and water intake and alters the activity of the hypothalamic-pituitary-adrenal (HPA) and gonadal (HPG) axes, but the relative involvement of RXFP3 and RXFP1 in these effects is not known. Therefore, the effects of icv administration of equimolar (1.1 nmol) amounts of RLN3 and the RXFP3-selective agonist RXFP3-A2 on food and water intake, plasma levels of corticosterone, testosterone, and oxytocin and c-fos mRNA expression in key hypothalamic regions in male rats were compared. Food intake was increased by both RLN3 and RXFP3-A2, but the orexigenic effects of RXFP3-A2 were significantly stronger than RLN3, 30 and 60min after injection. Water intake and plasma corticosterone and testosterone levels were significantly increased by RLN3, but not by RXFP3-A2. Conversely, RXFP3-A2 but not RLN3 decreased oxytocin plasma levels. RLN3, but not RXFP3-A2, increased c-fos mRNA levels in the parvocellular (PVNp) and magnocellular (PVNm) paraventricular and supraoptic (SON) hypothalamic nuclei, in the ventral medial preoptic area (MPAv), and in the organum vasculosum of the lamina terminalis (OVLT). A significant increase in c-fos mRNA expression was induced in the perifornical lateral hypothalamic area (LHApf) by RLN3 and RXFP3-A2. These results suggest that RXFP1 is involved in the RLN3 stimulation of water intake and activation of the HPA and HPG axes. The reduced food intake stimulation by RLN3 compared to RXFP3-A2 may relate to activation of both orexigenic and anorexigenic circuits by RLN3.

Role of relaxin-3/RXFP3 system in stress-induced binge-like eating in female rats.

Binge eating is frequently stimulated by stress. The neuropeptide relaxin-3 (RLN3) and its native receptor RXFP3 are implicated in stress and appetitive behaviors. We investigated the dynamics of the central RLN3/RXFP3 system in a newly established model of stress-induced binge eating. Female Sprague-Dawley rats were subjected to unpredictable intermittent 1-h access to 10% sucrose. When sucrose intake stabilized, rats were assessed for consistency of higher or lower sucrose intake in response to three unpredictable episodes of foot-shock stress; and assigned as binge-like eating prone (BEP) or binge-like eating resistant (BER). BEP rats displayed elevated consumption of sucrose under non-stressful conditions (30% > BER) and an additional marked increase in sucrose intake (60% > BER) in response to stress. Conversely, sucrose intake in BER rats was unaltered by stress. Chow intake was similar in both phenotypes on 'non-stress' days, but was significantly reduced by stress in BER, but not BEP, rats. After stress, BEP, but not BER, rats displayed a significant increase in RLN3 mRNA levels in the nucleus incertus. In addition, in response to stress, BEP, but not BER, rats had increased RXFP3 mRNA levels in the paraventricular and supraoptic nuclei of the hypothalamus. Intracerebroventricular administration of a selective RXFP3 antagonist, R3(B1-22)R, blocked the stress-induced increase in sucrose intake in BEP rats and had no effect on sucrose intake in BER rats. These results provide important evidence for a role of the central RLN3/RXFP3 system in the regulation of stress-induced binge eating in rats, and have therapeutic implications for eating disorders.