Motor-sparing peripatellar plexus block provides noninferior block duration and complete block area of the peripatellar region compared with femoral nerve block: a randomized, controlled, noninferiority study.

BACKGROUND: Developing adequate regional anaesthesia for knee surgeries without affecting lower limb mobilization is crucial to perioperative analgesia. However, reports in this regard are limited. We proposed a technique for ultrasound-guided peripatellar plexus (PP) block. Compared with the femoral nerve (FN) block, we hypothesized that this technique would provide a noninferior block duration and a complete cutaneous sensory block in the peripatellar region without affecting lower limb mobilization. An investigation was conducted to verify our hypothesis in cadavers and volunteers. METHODS: The study was designed in two parts. First, eight cadaveric lower limbs were dissected to verify the feasibility of PP block after methylene blue injection under ultrasound. Second, using a noninferiority study design, 50 healthy volunteers were randomized to receive either a PP block (PP group) or an FN block (FN group). The primary outcome was the duration of peripatellar cutaneous sensory block, with the prespecified noninferiority margin of -3.08 h; the secondary outcome was the area of peripatellar cutaneous sensory block; in addition, the number of complete anaesthesias of the incision line for total knee arthroplasty and the Bromage score 30 min after block were recorded. RESULTS: The PP was successfully dyed, whereas the FN and saphenous nerve were unstained in all cadaveric limbs. The mean difference of the block duration between the two groups was - 1.24 (95% CI, -2.81 - 0.33) h, and the lower boundary of the two-sided 95% CI was higher than the prespecified noninferiority margin (Pnoninferiority = 0.023), confirming the noninferiority of our technique over FN block. The cutaneous sensory loss covered the entire peripatellar region in the PP group. PP block achieved complete anaesthesia of the incision line used for total knee arthroplasty and a Bromage score of 0 in 25 volunteers, which differed significantly from that of volunteers who underwent FN block. CONCLUSION: Ultrasound-guided PP block is a feasible technique. Compared with FN block, PP block provides noninferior block duration and complete blocking of the peripatellar region without affecting lower limb mobilization. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Register (registration no. ChiCTR2000041547, registration date 28/12/2020).

Identification and Validation of Three Hub Genes Involved in Cell Proliferation and Prognosis of Castration-Resistant Prostate Cancer.

Background: The acquisition of castration resistance is lethal and inevitable in most prostate cancer patients under hormone therapy. However, effective biomarkers and therapeutic targets for castration-resistant prostate cancer remain to be defined. Methods: Comprehensive bioinformatics tools were used to screen hub genes in castration-resistant prostate cancer and were verified in androgen-dependent prostate cancer and castration-resistant prostate cancer in TCGA and the SU2C/PCF Dream Team database, respectively. Gene set enrichment analysis and in vitro experiments were performed to determine the potential functions of hub genes involved in castration-resistant prostate cancer progression. Results: Three hub genes were screened out by bioinformatics analysis: MCM4, CENPI, and KNTC1. These hub genes were upregulated in castration-resistant prostate cancer and showed high diagnostic and prognostic value. Moreover, the expression levels of the hub genes were positively correlated with neuroendocrine prostate cancer scores, which represent the degree of castration-resistant prostate cancer aggression. Meanwhile, in vitro experiments confirmed that hub gene expression was increased in castration-resistant prostate cancer cell lines and that inhibition of hub genes hindered cell cycle transition, resulting in suppression of castration-resistant prostate cancer cell proliferation, which confirmed the gene set enrichment analysis results. Conclusions: MCM4, CENPI, and KNTC1 could serve as candidate diagnostic and prognostic biomarkers of castration-resistant prostate cancer and may provide potential preventive and therapeutic targets.

Morphine inhibits sleep-promoting neurons in the ventrolateral preoptic area via mu receptors and induces wakefulness in rats.

Morphine is the most efficacious and widely prescribed treatment for pain. However, it decreases the total amount of deep sleep and rapid eye movement sleep in humans. Acute morphine administration at low doses causes wakefulness in animal models. To clarify the mechanism by which morphine affects sleep-wake behavior, we investigated the effects of morphine on the sleep-promoting neurons of the ventrolateral preoptic area (VLPO), a putative sleep-active nucleus, using in vitro brain slices by the patch-clamp technique. We also examined the effects of morphine on sleep-wake profiles after administration of opioid receptor antagonist to the VLPO using EEG and electromyogram recordings in freely moving rats. The results showed that morphine inhibited the firing rate of sleep-promoting neurons and hyperpolarized their membrane potentials without affecting interneurons in the VLPO. Morphine-induced hyperpolarization of membrane potentials could be reversed by, D-Phe-Cys-Thr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), a mu receptor antagonist, in the presence of tetrodotoxin. However, after the mu receptors were blocked by CTOP, morphine still suppressed the firing of the sleep-promoting neurons. This effect was antagonized by nor-BIN, a kappa receptor antagonist. Activation of kappa receptor by U50488H inhibited the firing of the sleep-promoting neurons. These results indicate that morphine could inhibit the activity of sleep-promoting neurons in the VLPO through mu and kappa receptors. EEG recordings revealed that morphine injected subcutaneously induced arousal in a dose-dependent manner. CTOP microinjected into VLPO antagonized the arousal effects of morphine, but nor-BIN did not. However, CTOP alone was not associated with any changes in the physiological sleep-wake cycle. Taken together, these findings clearly indicate that morphine inhibits sleep-promoting neurons in the VLPO by affecting mu receptors and so induces wakefulness in rats.

Honokiol promotes non-rapid eye movement sleep via the benzodiazepine site of the GABA(A) receptor in mice.

BACKGROUND AND PURPOSE: Decoctions of the Chinese herb houpu contain honokiol and are used to treat a variety of mental disorders, including depression. Depression commonly presents alongside sleep disorders and sleep disturbances, which appear to be a major risk factor for depression. Here, we have evaluated the somnogenic effect of honokiol and the mechanisms involved. EXPERIMENTAL APPROACH: Honokiol was administered i.p. at 20:00 h in mice. Flumazenil, an antagonist at the benzodiazepine site of the GABA(A) receptor, was administered i.p. 15 min before honokiol. The effects of honokiol were measured by EEG and electromyogram (EMG), c-Fos expression and in vitro electrophysiology. KEY RESULTS: Honokiol (10 and 20 mg·kg⁻¹) significantly shortened the sleep latency to non-rapid eye movement (non-REM, NREM) sleep and increased the amount of NREM sleep. Honokiol increased the number of state transitions from wakefulness to NREM sleep and, subsequently, from NREM sleep to wakefulness. However, honokiol had no effect on either the amount of REM sleep or EEG power density of both NREM and REM sleep. Honokiol increased c-Fos expression in ventrolateral preoptic area (VLPO) neurons, as examined by immunostaining, and excited sleep-promoting neurons in the VLPO by whole-cell patch clamping in the brain slice. Pretreatment with flumazenil abolished the somnogenic effects and activation of the VLPO neurons by honokiol. CONCLUSION AND IMPLICATIONS: Honokiol promoted NREM sleep by modulating the benzodiazepine site of the GABA(A) receptor, suggesting potential applications in the treatment of insomnia, especially for patients who experience difficulty in falling and staying asleep.