Electrochemical Oxidative C(sp2)-H Amination of Aldehyde Hydrazones with Azoles.

A general and highly efficient method for the electrochemical C(sp2)-H amination of aldehyde hydrazones with azoles has been developed. This reaction proceeds under exogenous metal-, catalyst-, and oxidant-free conditions to provide aminated hydrazone derivatives in good to excellent yields. This strategy applies to both aromatic and aliphatic aldehyde hydrazones and tolerates a broad range of functional groups.

Determining the Minimum Effective Concentration of Ropivacaine in Epidural Anesthesia for Tolerable Pain in Transforaminal Percutaneous Endoscopic Lumbar Discectomy to Avoid Nerve Injury: A Double-Blind Study Using a Biased-Coin Design.

PURPOSE: Epidural anesthesia (EA) is the main anesthesia method for transforaminal percutaneous endoscopic lumbar discectomy (PELD). Reducing the concentration of ropivacaine can help preserve tactile sensation, allowing patients to provide timely feedback to the surgeons when a nerve root is contacted to avoid nerve injury. Therefore, a 90% effective concentration (EC90) that allows for mild pain [visual analog scale (VAS) score ≤3] while maximizing tactile sensation must be identified. METHODS: The concentration of ropivacaine for EA was varied for consecutive patients in this study using a two-stage biased-coin design (BCD) according to the response of the previous patient; the concentration used for the first patient was 0.2%. When the previous patient had a negative response (VAS score >3), the concentration used for the next one was increased by 0.015%. When the previous patient had a positive response (VAS score ≤3), the concentration used for the next one had an 89% probability of remaining the same and an 11% probability of being reduced by 0.015%. The EC90 of ropivacaine was estimated using isotonic regression, and the 95% confidence interval (CI) was estimated using the bootstrapping method in R. RESULTS: A total of 58 patients were included in the study. The calculated EC90 was 0.294% [95% CI (0.271%, 0.303%)]. Among 13 patients who reported unintended nerve root contact during the operation, none were found to have irreversible nerve injury after the operation. CONCLUSION: To preserve maximum tactile sensation, the EC90 of ropivacaine was 0.294% for patients with allowed mild pain. This concentration could allow for timely feedback when the nerve root is contacted, to avoid nerve injury.

Effect Analysis of Epidural Anesthesia with 0.4% Ropivacaine in Transforaminal Endoscopic Surgery.

Background: Epidural anesthesia used in percutaneous endoscopic lumber discectomy (PELD) has the risk of complete neurotactile block. Patients cannot timely respond to the operator when the nerve is touched by mistake, so the potential risk of nerve injury cannot be avoided. According to pharmacodynamics, with the decrease of local anesthetic concentration, the nerve tactile gradually recovered; however, the analgesic effect also gradually weakened. Therefore, it is necessary to explore an appropriate concentration of local anesthetics that can keep the patients' nerve touch without pain. By comparing the advantages and disadvantages of 0.4% ropivacaine epidural anesthesia, local anesthesia and intravenous anesthesia on intraoperative circulation fluctuation, the incidence of salvage analgesia and the incidence of nerve non-touch, the feasibility of using low concentration epidural anesthesia in PELD to obtain enough analgesia and avoid the risk of nerve injury was confirmed. Methods: 153 cases of intervertebral foramen surgery from October 2017 to January 2020 were selected and divided into local anesthesia group (LA group), 0.4% ropivacaine epidural anesthesia group (EA group), and intravenous anesthesia group (IVA group) according to different anesthesia methods. The changes of blood pressure and heart rate, the incidence of rescue analgesia and nerve root non-touch were compared among the three groups. Results: The difference of map peak value among the three groups was statistically significant (P < 0.001); pairwise comparison showed that the map peak value of the LA group was higher than that of the EA group (P < 0.001) and IVA group (P < 0.001), but there was no statistical significance between the EA group and IVA group. The difference of HR peak value among the three groups was statistically significant; pairwise comparison showed that the HR peak value of the LA group was higher than that of the EA group (P < 0.001) and IVA group (P < 0.001), but there was no statistical significance between the EA group and IVA group. There was significant difference in the incidence of intraoperative hypertension among the three groups (P < 0.05); pairwise comparison showed that the incidence of intraoperative hypertension in the EA group was lower than that in the LA group (P < 0.05), while there was no significant difference between the IVA group, EA group, and LA group. There was significant difference in the incidence of rescue analgesia among the three groups (P < 0.01); pairwise comparison showed that the incidence of rescue analgesia in the EA group was lower than that in the LA group (P < 0.05) and IVA group (P < 0.05), but there was no significant difference between the LA group and IVA group. Due to the different analgesic mechanisms of the three anesthesia methods, local anesthesia and intravenous anesthesia do not cause the loss of nerve tactile, while the incidence of nerve tactile in 0.4% ropivacaine epidural anesthesia is only 2.4%, which is still satisfactory. Conclusion: Epidural anesthesia with 0.4% ropivacaine is a better anesthesia method for PELD. It not only has a low incidence of non-tactile nerve, but also has perfect analgesia and more stable intraoperative circulation.

Effect of ADRA2A gene polymorphisms on the anesthetic and analgesic effects of dexmedetomidine in Chinese Han women with cesarean section.

It is well known that differences in drug reactions among individuals are widespread, and therefore the study of genetic polymorphisms of drug targets has become a research hotspot. Dexmedetomidine is clinically effective by acting on α2 adrenergic receptor and the impact of the adrenoceptor α2A gene (ADRA2A) polymorphisms on the anesthetic and analgesic effects of dexmedetomidine is related to the clinical application of dexmedetomidine. The present study aimed to analyze the effects of the rs1800035, rs201376588 and rs775887911 locus single-nucleotide polymorphisms of the ADRA2A on the anesthetic and analgesic effects of dexmedetomidine in Chinese Han women. A total of 434 Chinese women undergoing cesarean section were enrolled in this study. A 3-ml fasting venous blood sample was collected from all subjects for genomic DNA extraction and genotype detection. The pre-anesthetic and post-anesthetic pain threshold (PTh), pain tolerance threshold (PTTh), mean arterial pressure, heart rate, blood oxygen saturation, cortisol (Cor) content, blood glucose (Glu) content, opioid usage, patient-controlled analgesia pressing times, surgical satisfaction and postoperative adverse reactions were recorded. The visual analogue scale (VAS) and Ramsay sedation score were evaluated. PTh and PTTh in the wild-type women were higher than those in the women with mutations (P<0.05). The postoperative VAS scores of wild-type women were lower than those of mutants (P<0.05). The Ramsay sedation scores of wild-type patients at 12 h after the operation were significantly higher than in those with mutations (P<0.05). The levels of Cor and Glu in women with mutations were significantly higher than those of wild-type women at 12, 24 and 48 h after surgery (P<0.05). The satisfaction with surgery of wild-type patients was higher than that of patients with mutations (P<0.05). Gene mutations of rs1800035, rs201376588 and rs775887911 loci in the ADRA2A gene reduced the anesthetic and analgesic effect during and after cesarean section in Chinese Han women. Postoperative analgesia of mothers with mutations may require higher doses of analgesics.

MicroRNA-212-3p Attenuates Neuropathic Pain via Targeting Sodium Voltage-gated Channel Alpha Subunit 3 (NaV 1.3).

PURPOSE: To explore the role and potential mechanism of miR-212-3p in neuropathic pain regulation. METHODS: Adult male rats were used to establish chronic constriction injury (CCI) model to mimic the neuropathic pain. Then, paw withdrawal threshold (PWT) and paw withdrawal thermal latency (PWL) were determined. The concentrations of interleukin 1 beta (IL-1ß), interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were measured with enzyme-linked immune sorbent assay (ELISA) kit and the expression of miR-212-3p was measured by real time quantitative PCR (RTqPCR). Besides, miR-212-3p agomir was intrathecally injected into CCI rats and the expression of key apoptotic proteins was determined by western blot. Furthermore, dual-luciferase reporter assay was used to determine the binding of miR-212-3p and 3' untranslated regions (3'UTR) of NaV1.3 and the expression levels of NaV1.3 were measured by western blot and RT-qPCR. RESULTS: In the CCI group, the PWT and PWL were significantly decreased and IL-1ß, IL-6 and TNF-α were increased. miR-212-3p was decreased in response to CCI. The intrathecal injection of miR-212-3p agomir into CCI rats improved the PWT and PWL, decreased the IL-1ß, IL-6 and TNF-α, decreased the expression levels of BCL2 associated X, apoptosis regulator (Bax), cleaved caspase-3 and increased the expression levels of BCL2 apoptosis regulator (Bcl-2). The results of dual--luciferase reporter assay showed that miR-212-3p could directly bind with 3'UTR of NaV1.3. The expression of NaV1.3 was up-regulated in CCI rats who were intrathecally injected with miRctrl, whereas it decreased in CCI rats intrathecally injected with miR-212-3p agomir. CONCLUSION: The expression of miR-212a-3p attenuates neuropathic pain by targeting NaV1.3.