Calhm2 has an important role in microglial activation and contributes to Alzheimer’s disease pathology.

Corticotropin releasing factor (CRF) network in the oval nucleus of bed nuclei of the stria terminalis (ovBNST) is generally indicated in stress, but its role in female-biased susceptibility to anxiety is unknown. Here, we established a female-biased stress paradigm. We found that the CRF release in ovBNST during stress showed female-biased pattern, and ovBNST CRF neurons were more prone to be hyperexcited in female mice during stress in both in vitro and in vivo studies. Moreover, optogenetic modulation to exchange the activation pattern of ovBNST CRF neurons during stress between female and male mice could reverse their susceptibility to anxiety. Last, CRF receptor type 1 (CRFR1) mediated the CRF-induced excitation of ovBNST CRF neurons and showed female-biased expression. Specific knockdown of the CRFR1 level in ovBNST CRF neurons in female or overexpression that in male could reverse their susceptibility to anxiety. Therefore, we identify that CRFR1-mediated hyperexcitation of ovBNST CRF neurons in female mice encode the female-biased susceptibility to anxiety.

Background: Liposomal bupivacaine (LB) can provide prolonged analgesia, which may reduce patients’ opioid consumption, improve comfort, and facilitate recovery. Looser tissue and lower vascularity in the paravertebral space may facilitate LB diffusion and duration, so we investigated the effects of LB in multimodal analgesia after thoracic surgery with paravertebral block. Methods: In this single-center, double-blind, randomized, parallel-controlled trial, 102 patients undergoing elective thoracoscopic surgery were randomized 1:1 to thoracic paravertebral block with LB (6.67 mg/mL) or ropivacaine hydrochloride (RH; 0.33%). The primary outcome was opioid consumption within 72 h postoperatively. Secondary outcomes included pain ratings at 6, 12, 24, 48, and 72 h postoperatively; rescue analgesia; time to first ambulation and defecation; post-anesthesia care unit and hospital length of stay; and adverse events. Results: One patient was excluded due to block failure, leaving 101 patients (LB group, n = 51; RH group, n = 50). LB significantly reduced 72-h opioid consumption compared to RH (difference = – 181.4 mg; 95% CI: – 232.8, – 130.0 mg; P < 0.001), and fewer patients in the LB group required rescue analgesia compared to the RH group (OR: 0.33; 95% CI: 0.13, 0.82; P < 0.05). Pain scores at 24 h were lower in the LB group than RH group (difference = – 0.44; 95% CI: – 0.84, – 0.04; P < 0.05), with no differences at other timepoints. The LB group had shorter time to first ambulation than the RH group [median time (IQR): 20 (18– 24) h vs 26 (22– 32) h; HR: 3.81; 95% CI: 2.32, 6.19; P < 0.001] and shorter time to defecation [median time (IQR): 56 (42– 65) h vs 72 (57– 80) h; HR: 3.98; 95% CI: 2.46, 6.44; P < 0.001]. Conclusion: Ultrasound-guided paravertebral block with LB may reduce postoperative opioid consumption and enhance recovery in patients undergoing thoracic surgery. Trial Registration: Chinese Clinical Trials Registry Platform (chictr.org.cn): ChiCTR2400091217.