A multi-center study to predict the risk of intraoperative hypothermia in gynecological surgery patients using preoperative variables.

OBJECTIVES: Hypothermia is highly common in patients undergoing gynecological surgeries under general anesthesia, so the length of hospitalization and even the risk of mortality are substantially increased. Our aim was to develop a simple and practical model to preoperatively identify gynecological surgery patients at risk of intraoperative hypothermia. METHODS: In this retrospective study, we collected data from 802 patients who underwent gynecological surgery at three medical centers from June 2022 to August 2023. We further allocated the patients to a training group, an internal validation group, or an external validation group. The preliminary predictive factors for intraoperative hypothermia in gynecological patients were determined using the least absolute shrinkage and selection operator (LASSO) method. The final predictive factors were subsequently identified through multivariate logistic regression analysis, and a nomogram for predicting the occurrence of hypothermia was established. RESULTS: A total of 802 patients were included, with 314 patients in the training cohort (mean age 48.5 ± 12.6 years), 130 patients in the internal validation cohort (mean age 49.9 ± 12.5 years), and 358 patients in the external validation cohort (mean age 47.6 ± 14.0 years). LASSO regression and multivariate logistic regression analyses indicated that body mass index, minimally invasive surgery, baseline heart rate, baseline body temperature, history of previous surgery, and aspartate aminotransferase level were associated with intraoperative hypothermia in gynecological surgery patients. This nomogram was constructed based on these six variables, with a C-index of 0.712 for the training cohort. CONCLUSIONS: We established a practical predictive model that can be used to preoperatively predict the occurrence of hypothermia in gynecological surgery patients. CLINICAL TRIAL REGISTRATION: chictr.org.cn, identifier ChiCTR2300071859.

Immune system changes in those with hypertension when infected with SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) outbreak has become an evolving global health crisis. With an increasing incidence of primary hypertension, there is greater awareness of the relationship between primary hypertension and the immune system [including CD4+, CD8+ T cells, interleukin-17 (IL-17)/T regulatory cells (Treg) balance, macrophages, natural killer (NK) cells, neutrophils, B cells, and cytokines]. Hypertension is associated with an increased risk of various infections, post-infection complications, and increased mortality from severe infections. Despite ongoing reports on the epidemiological and clinical features of COVID-19, no articles have systematically addressed the role of primary hypertension in COVID-19 or how COVID-19 affects hypertension or specific treatment in these high-risk groups. Here, we synthesize recent advances in understanding the relationship between primary hypertension and COVID-19 and its underlying mechanisms and provide specific treatment guidelines for these high-risk groups.

Efficacy and safety of rhomboid intercostal block for analgesia in breast surgery and thoracoscopic surgery: a meta-analysis.

BACKGROUND: Rhomboid intercostal block (RIB) is a new regional anesthesia technique that provides postoperative analgesia for breast surgery and thoracoscopic surgery. The published papers are not yet fully integrated and do not adequately address the impact and safety of the RIB on postoperative pain. METHODS: The PubMed, Web of Science and Embase were searched from 2016 to 2021 for all available randomized controlled trials (RCTs) that evaluated the analgesic efficacy and safety of RIB after thoracic surgery and breast surgery. Random and fixed-effects meta-analytical models were used where indicated, and between-study heterogeneity was assessed. The primary outcome was Postoperative Numerical Rating Scale (NRS) scores of patients at rest recorded 0-1, 6-8, 24 h after surgery. The secondary outcomes included rate of postoperative nausea and vomiting (PONV), postoperative fentanyl consumption and presence of complications of the block. RESULTS: From 81 records identified, four studies met our inclusion criteria, including 216 patients (RIB:108 patients; no block: 108 patients). In the primary outcome, RIB group showed significantly lower postoperative NRS at rest at first 0-1 h and 6-8 h (weighted mean difference [WMD] = -1.55; 95% confidence internal [CI] = -2.92 to -0.19; p < 0.05), (WMD = -0. 69; 95% CI = -1.29 to -0. 09; p < 0. 05). And there was no significant difference between groups in NRS at rest at 24 h (WMD = -0.78; 95% CI = -1.64 to -0.08; p = 0.77). Also, RIB group showed significantly lower postoperative NRS of breast surgery and thoracoscopic surgery at 0-1 h (WMD = -3.00; 95% CI = -3.13 to -2.87; p < 0.01), (WMD = -1.08; 95% CI = -1.98 to -0.18; p < 0.05). In the secondary outcome, the analysis also showed RIB group had significant lower of POVN rates (summary relative risk (RR) = 0.212;95%CI = 0.10 to 0.45; p < 0. 01) and the postoperative consumption of fentanyl (WMD = -57.52;95%CI = -106.03 to -9.02; p < 0. 05). CONCLUSION: This review shows that RIB was more effective in controlling acute pain after breast surgery and thoracoscopic surgery than general analgesia. And it is a trend that RIB may be a kind of effective and safe nerve bock technology and it requires further studies.

Increased Hyperalgesia and Proinflammatory Cytokines in the Spinal Cord and Dorsal Root Ganglion After Surgery and/or Fentanyl Administration in Rats.

BACKGROUND: Perioperative fentanyl has been reported to induce hyperalgesia and increase postoperative pain. In this study, we tried to investigate behavioral hyperalgesia, the expression of proinflammatory cytokines, such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and the activation of microglia in the spinal cord and dorsal root ganglion (DRG) in a rat model of surgical plantar incision with or without perioperative fentanyl. METHODS: Four groups of rats (n = 32 for each group) were subcutaneously injected with fentanyl at 60 µg/kg or normal saline for 4 times with 15-minute intervals. Plantar incisions were made to rats in 2 groups after the second drug injection. Mechanical and thermal nociceptive thresholds were assessed by the tail pressure test and paw withdrawal test on the day before, at 1, 2, 3, 4 hours, and on the days 1-7 after drug injection. The lumbar spinal cord, bilateral DRG, and cerebrospinal fluid of 4 rats in each group were collected to measure IL-1ß, IL-6, and TNF-α on the day before, at the fourth hour, and on the days 1, 3, 5, and 7 after drug injection. The lumbar spinal cord and bilateral DRG were removed to detect the ionized calcium-binding adapter molecule 1 on the day before and on the days 1 and 7 after drug injection. RESULTS: Rats injected with normal saline only demonstrated no significant mechanical or thermal hyperalgesia or any increases of IL-1ß, IL-6, and TNF-α in the spinal cord or DRG. However, injection of fentanyl induced analgesia within as early as 4 hours and a significant delayed tail mechanical and bilateral plantar thermal hyperalgesia after injections lasting for 2 days, while surgical plantar incision induced a significant mechanical and thermal hyperalgesia lasting for 1-4 days. The combination of fentanyl and incision further aggravated the hyperalgesia and prolonged the duration of hyperalgesia. The fentanyl or surgical incision upregulated the expression of IL-1ß, IL-6, and TNF-α in the spinal cord and bilateral DRG for more than 7 days and increase of ionized calcium-binding adapter molecule 1 in the spinal cord. The combination of fentanyl and incision resulted in higher increase of IL-1ß, IL-6, and TNF-α in the spinal cord and bilateral DRG. CONCLUSIONS: The surgical plantar incision with or without perioperative fentanyl induced significant mechanical and thermal hyperalgesia, an increased expression of IL-1ß, IL-6, TNF-α in the spinal cord and DRG, and activation of microglia in the spinal cord.

Double-injection technique assisted by a nerve stimulator for ultrasound-guided supraclavicular brachial plexus block results in better distal sensory-motor block: A randomised controlled trial.

BACKGROUND: To evaluate the efficacy of a nerve stimulator when used with ultrasound-guided double injection in supraclavicular brachial plexus block. OBJECTIVES: We hypothesised that targeting the inferior trunk of the plexus guided by a nerve stimulator would obtain a higher success rate of ulnar nerve blockade than the traditional double-injection technique. DESIGN: A blinded randomised controlled study. SETTING: Conducted at the University Hospital from October 2015 to January 2016. PATIENTS: Ninety patients undergoing upper extremity surgery were randomised into two equal groups. INTERVENTIONS: Patients were randomly allocated to a modified double-injection group (MDI group) or a traditional double-injection group (DI group). All patients received 23 ml of a 1 : 1 mixture of 2% lidocaine and 1% ropivacaine during ultrasound-guided supraclavicular brachial plexus block. In the MDI group (n = 45), half the volume was deposited within the brachial plexus sheath guided by ultrasound, next to the inferior trunk and verified by nerve stimulation; the remaining volume was deposited in the main neural cluster. In the double-injection group (n = 45), the first half volume was deposited on ultrasound guidance alone. Sensory-motor blockade of the musculocutaneous, median, radial, ulnar nerves and surgical anaesthesia, performance time, number of needle passes and complications were recorded. MAIN OUTCOME MEASURES: The success rate of complete sensory block of the ulnar nerve within 15 min after local anaesthetic injection. RESULTS: Compared with the DI group the MDI group had higher success rates of complete sensory block of the ulnar nerve (93 vs 67%, P = 0.002) and complete anaesthesia (80 vs 56%, P = 0.014) at 15 min, whereas the average performance time was significantly longer (5.08 ±â€Š1.41 vs 4.10 ±â€Š0.64 min, P < 0.001) and the number of needle passes was significantly higher (4.40 ±â€Š1.14 vs 2.87 ±â€Š0.79, P < 0.001). CONCLUSION: The MDI technique has a higher success rate for complete sensory block of the ulnar nerve within 15 min of local anaesthetic injection. The time needed to perform the block is about 1 min longer than the traditional technique. TRIAL REGISTRATION: http://www.chictr.org.cn with the registration number of ChiCTR-IOR-15007588.

Midazolam inhibits the proliferation of human head and neck squamous carcinoma cells by downregulating p300 expression.

The objective of this study was to investigate the mechanism of midazolam in inhibiting the proliferation of hypopharyngeal squamous carcinoma cells. Cultured FaDu cancer cells were treated with different concentrations of midazolam. MTT and BrdU incorporation assays were then used to evaluate cancer cell proliferation. The mRNA and protein levels of p300, a key factor involved in the tumorigenesis of numerous cancers, were measured with RT-PCR and Western blotting, respectively. Midazolam inhibited the expression of p300 and the proliferation of FaDu cells. Additionally, knockdown of p300 resulted in increased expression of p21 and p27 and decreased expression of p-Rb while inhibiting the proliferation of FaDu cells. Midazolam inhibits the proliferation of human head and neck squamous carcinoma cells by downregulating p300. Midazolam may be useful for the treatment of hypopharyngeal squamous cancers.

Effectiveness of general anaesthesia with remimazolam tosilate on intraoperative haemodynamics and postoperative recovery: study protocol for a randomised, positive-controlled, pragmatic clinical trial (GARTH trial).

INTRODUCTION: It is encouraged to estimate the effectiveness of components within the enhanced recovery after surgery (ERAS) protocol through patient-reported outcomes, alongside doctor-reported outcomes and length of hospital stay. At present, studies on the contributions of optimal anaesthetic drugs within the ERAS protocol to patient-reported and doctor-reported outcomes are limited. Therefore, this study aims to pragmatically evaluate the effectiveness and safety of general anaesthesia (GA) with remimazolam tosilate within the ERAS protocol on intraoperative haemodynamics and postoperative recovery in adults undergoing elective surgeries, compared with propofol. METHODS AND ANALYSIS: This study is a single-centre, randomised, blinded, positive-controlled, pragmatic clinical trial. A total of 900 patients, aged ≥18 years old, scheduled for an elective surgical procedure under GA will be included. Patients will be randomised in a 1:1 ratio to the remimazolam group (the GA with remimazolam tosilate within the ERAS protocol group) or propofol group (the GA with propofol within the ERAS protocol group), stratified by general surgery, thoracic surgery and other surgeries (including urological surgery and otolaryngology surgery). The primary outcomes include the 24-hour postoperative quality of recovery-40 score and the rate of intraoperative hypotension. Secondary endpoints include the rate of sedative hypotension requiring treatment, the haemodynamic profiles, the 72-hour postoperative quality of recovery-40 score, the functional anaesthetic capability, adverse events and complications, quality of life within 3 months as well as economic health outcomes. ETHICS AND DISSEMINATION: This study protocol has been approved by the ethics committee of Guangdong Provincial People's Hospital (KY-H-2022-005-03-08). Dissemination plans will be presented at scientific meetings and in scientific publications. TRIAL REGISTRATION NUMBER: ChiCTR2200062520.

ATF4 inhibits TRPV4 function and controls itch perception in rodents and nonhuman primates.

ABSTRACT: Acute and chronic itch are prevalent and incapacitating, yet the neural mechanisms underlying both acute and chronic itch are just starting to be unraveled. Activated transcription factor 4 (ATF4) belongs to the ATF/CREB transcription factor family and primarily participates in the regulation of gene transcription. Our previous study has demonstrated that ATF4 is expressed in sensory neurons. Nevertheless, the role of ATF4 in itch sensation remains poorly understood. Here, we demonstrate that ATF4 plays a significant role in regulating itch sensation. The absence of ATF4 in dorsal root ganglion (DRG) neurons enhances the itch sensitivity of mice. Overexpression of ATF4 in sensory neurons significantly alleviates the acute and chronic pruritus in mice. Furthermore, ATF4 interacts with the transient receptor potential cation channel subfamily V member 4 (TRPV4) and inhibits its function without altering the expression or membrane trafficking of TRPV4 in sensory neurons. In addition, interference with ATF4 increases the itch sensitivity in nonhuman primates and enhances TRPV4 currents in nonhuman primates DRG neurons; ATF4 and TRPV4 also co-expresses in human sensory neurons. Our data demonstrate that ATF4 controls pruritus by regulating TRPV4 signaling through a nontranscriptional mechanism and identifies a potential new strategy for the treatment of pathological pruritus.

Loss expression of PHLPP1 correlates with lymph node metastasis and exhibits a poor prognosis in patients with gastric cancer.

BACKGROUND: PHLPP1 functions as an antitumor factor in several human cancers, but the expression pattern and clinical significance of PHLPP1 in gastric cancer have yet to be determined. The aim of this study is to assess the expression of PHLPP1 in gastric cancer and its impact on the prognosis of patients with gastric cancer. METHODS: A total of 202 consecutive patients with gastric cancer who had undergone gastrectomy were enrolled in this study. The expressions of PHLPP1 were assessed by immunohistochemistry method. Survival analysis according to PHLPP1 expression was calculated. RESULTS: The positive rates of PHLPP1 protein in primary gastric cancer tissues and metastatic lymph nodes were significantly lower than in normal stomach mucosa tissues (56.9% vs. 96.7%, 38.8% vs. 96.7%, both P < 0.001). The overall survival (OS) time and relapse-free survival (RFS) time in PHLPP1-positive patients were significantly longer than in PHLPP1-negative patients (both P < 0.001). Moreover, PHLPP1 was an independent prognostic factor for OS and RFS of gastric cancer patients (HR 0.55, 95% CI 0.36-0.85, P = 0.007; HR 0.52, 95% CI 0.31-0.87, P = 0.013; respectively). CONCLUSIONS: The loss expression of PHLPP1 was observed in gastric cancer and PHLPP1 is an independent prognostic factor for patients with gastric cancer.

Construction of a risk index system for the prediction of chronic post-surgical pain after video-assisted thoracic surgery for lung resection: A modified Delphi study.

In the present study, several research methods were adopted, including literature retrieval, theoretical analysis, and qualitative research, and then the draft of the prognostic factors for the chronic post-surgical pain (CPSP) index system after video-assisted thoracoscopic surgery (VATS) for lung resection was constructed. A Delphi survey was used for the study of 24 experts in the field of pain from three different grade-A tertiary hospitals in Guangzhou, China. In the two rounds of survey, the experts rated these indicators for the importance and feasibility of measurement (round 1, n = 21 participants; round 2, n = 20). Finally, we calculated Kendall's W index as a measure of consensus. A general consensus was reached on predicting CPSP after VATS, consisting of 10 first-level domains and 64 second-level indicators, involving biological, psychological and social perspectives. This study provides a comprehensive draft of risk factors developed and identified by experts to inform research-based evidence on chronic pain. Increased clinical awareness and a full understanding of how to screen and identify people with CPSP problems may lead to earlier recognition of chronic pain and greater facilitation of professional prevention.

Ultrasound-guided brachial plexus block at the clavicle level: A review.

The supraclavicular block (SCB) and the infraclavicular block (ICB) are introduced to meet upper extremity surgery, where the transducer or the insertion point is placed superiorly and inferiorly at the approximate midpoint of the clavicle, respectively. These two approaches are highly appealing since they clearly exhibited each cord and its associated anatomy. In addition, it directed the needle accurately with real-time imaging by ultrasound guidance. Therefore, it brought higher success rates and fewer complications. Numerous trials have recently been conducted to examine the SCB and ICB regarding the new approach, injection techniques, block dynamics, and complication of hemidiaphragmatic paresis. It was found that both approaches could improve block effectiveness and postoperative analgesia for upper extremity surgery, according to recent studies at the level of the clavicular brachial plexus block. However, there is still a lack of work comparing the clinical performance and effectiveness of both approaches with ultrasonography. This review aims to outline the current available data from clinical trials along with case reports about these two approaches and to describe the findings published in the literature during the previous 5 years. Based on these findings, we attempt to determine whether there exists a one-size-fits-all approach that has the potential to meet upper extremity surgery.

A single dose of ketamine relieves fentanyl-induced-hyperalgesia by reducing inflammation initiated by the TLR4/NF-κB pathway in rat spinal cord neurons.

A large amount of clinical evidence has revealed that ketamine can relieve fentanyl-induced hyperalgesia. However, the underlying mechanism is still unclear. In the current study, a single dose of ketamine (5 mg/kg or 10 mg/kg), TAK-242 (3 mg/kg), or saline was intraperitoneally injected into rats 15 min before four subcutaneous injections of fentanyl. Results revealed that pre-administration of ketamine alleviated fentanyl-induced hyperalgesia according to hind paw-pressure and paw-withdrawal tests. High-dose ketamine can reverse the expression of toll-like receptor-dimer (d-TLR4), phospho- nuclear factor kappa-B (p-NF-κB, p-p65), cyclooxygenase-2 (COX-2), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) 1 d after fentanyl injection in the spinal cord. Moreover, fentany-linduced-hyperalgesia and changes in the expression of the aforementioned proteins can be attenuated by TAK-242, an inhibitor of TLR4, as well as ketamine. Importantly, TLR4, p-p65, COX-2, and IL-1ß were expressed in neurons but not in glial cells in the spinal cord 1 d after fentanyl injection. In conclusion, results suggested that a single dose of ketamine can relieve fentanyl-induced-hyperalgesia via the TLR4/NF-κB pathway in spinal cord neurons.

Multiple-, but not single-, dose of parecoxib reduces shoulder pain after gynecologic laparoscopy.

BACKGROUND: The aim of this study was to investigate effect of single- and multiple-dose of parecoxib on shoulder pain after gynecologic laparoscopy. METHODS: 126 patients requiring elective gynecologic laparoscopy were randomly allocated to three groups. Group M (multiple-dose): receiving parecoxib 40mg at 30min before the end of surgery, at 8 and 20hr after surgery, respectively; Group S (single-dose): receiving parecoxib 40mg at 30min before the end of surgery and normal saline at the corresponding time points; Group C (control): receiving normal saline at the same three time points. The shoulder pain was evaluated, both at rest and with motion, at postoperative 6, 24 and 48hr. The impact of shoulder pain on patients' recovery (activity, mood, walking and sleep) was also evaluated. Meanwhile, rescue analgesics and complications were recorded. RESULTS: The overall incidence of shoulder pain in group M (37.5%) was lower than that in group C (61.9%) (difference=-24.4%; 95% CI: 3.4~45.4%; P=0.023). Whereas, single-dose regimen (61.0%) showed no significant reduction (difference with control=-0.9%; 95% CI: -21.9~20.0%; P=0.931). Moreover, multiple-dose regimen reduced the maximal intensity of shoulder pain and the impact for activity and mood in comparison to the control. Multiple-dose of parecoxib decreased the consumption of rescue analgesics. The complications were similar among all groups and no severe complications were observed. CONCLUSIONS: Multiple-, but not single-, dose of parecoxib may attenuate the incidence and intensity of shoulder pain and thereby improve patients' quality of recovery following gynecologic laparoscopy.

Improving successful rate of transcranial electrical motor-evoked potentials monitoring during spinal surgery in young children.

INTRODUCTION: This prospective study was to investigate the successful rate of intraoperative motor evoked potentials (MEP) monitoring for children (<12 years old) with congenital scoliosis. MATERIALS AND METHODS: A consecutive series of 27 young children (7 girls and 20 boys; from 1 to 11 years old) between September 2007 and November 2009, were enrolled to this study. 12 patients received general anesthesia based on TIVA, induced with propofol 2-4 mg/kg and fentanyl 3-5 µg/kg followed by a continuous infusion of propofol (20-150 µg/kg/min, at mean of 71.7 µg/kg/min). The other 15 patients received combined inhalation and intravenous anesthesia, induced with sevoflurane and fentanyl 3-5 µg/kg and maintained by sevoflurane (0.5-1%). The maintenance of anaesthesia management was performed with stable physiological parameters during surgery. RESULTS: Intraoperative MEP monitoring was successfully performed in all patients, while SEP was successfully performed in 26 of 27 patients. There was no significant difference of successful rates between SEP and MEP monitoring (P > 0.05). As well, no difference in MEP successful rates was observed in two groups with different anesthetic techniques. No wake-up test and no post-operative neurological deficits occurred in this series of patients. CONCLUSION: Low dose anesthesia by either TIVA with propofol or sevoflurane-based mixture anesthesia protocol can help the intraoperative spinal cord monitoring to successfully elicit MEP and perform reliable monitoring for patients below 12 years of age.

Intertruncal versus classical approach to the ultrasound-guided supraclavicular brachial plexus block for upper extremity surgery: study protocol for a randomized non-inferiority trial.

BACKGROUND: Ultrasound-guided intertruncal approach (IA) to the supraclavicular block (SB) is recently proposed as a new approach for local anesthetic (LA) injection in terms of the classical approach (CA) at the level of the first rib. The CA-SB has been proven to result in satisfying sensorimotor block, but associate with a high risk of intraneural injection. The aim of this randomized non-inferiority study is to explore whether IA-SB can obtain similar block dynamics, as the CA-SB, but avoiding an intraneural injection during the whole nerve block procedure. METHODS: The total 122 patients undergoing elective upper extremity surgery will be randomly allocated to receive either an IA-SB or a CA-SB using a double-injection (DI) technique. In the IA-SB group, a portion of LA (15 mL) is injected accurately to the intertruncal plane between the middle and lower trunks under real-time ultrasound guidance; then, the remaining volume (10 mL) is carefully distributed to the other intertruncal plane between the upper and middle trunks. In the CA-SB group, the DI technique will be carried out as described in Tran's study. The primary outcome is the percentage of patients with a complete sensory blockade at 20 min with a predefined non-inferiority margin of - 5%. The secondary outcomes include the sensory-motor blockade of all 4 terminal nerves, onset times of the individual nerves within 30 min, block-related variables, and adverse events. DISCUSSION: The results will provide sensory-motor blockade-related parameters and safety of the ultrasound-guided intertruncal approach to the supraclavicular block, thereby promoting clinical practice. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000040199 . Registered on 25 November 2020.

Effects of double vs triple injection on block dynamics for ultrasound-guided intertruncal approach to the supraclavicular brachial plexus block in patients undergoing upper limb arteriovenous access surgery: study protocol for a double-blinded, randomized controlled trial.

BACKGROUND: Ultrasound-guided intertruncal approach (IA) has been proposed to be an alternative and promising approach to the supraclavicular block (SCB), in which double injection (DI) of local anesthetics (LA) is sequentially administered between intertruncal planes. We would like to apply a refined injection technique, named triple injection (TI) technique, based on the 3 separate compartments visualized by ultrasound. The aim of this study is to compare the percentage of patients with complete sensory blockade at 20 min of DI vs TI technique, when they are applied in patients undergoing upper limb arteriovenous access surgery. METHODS: This study is a prospective parallel-group randomized controlled trial. A total of 86 end-stage renal disease patients will be randomly allocated to receive IA-SCB using either DI or TI technique with identical LA (0.5% ropivacaine 24 mL). The primary outcome is the percentage of patients with complete sensory blockade of all 4 terminal nerves (median, ulnar, radial, and musculocutaneous nerves) of the brachial plexus measured at 20 min after injection. The secondary outcomes will consist of the sensory or motor blockade of all individual nerves, onset times, performance time, diaphragmatic paralysis, surgical anesthesia, and adverse events. DISCUSSION: It is expected that ultrasound-guided IA-SCB with the TI technique results in better block dynamic in patients undergoing upper limb arteriovenous access surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100045075 .

Pentazocine-induced antinociception is mediated mainly by µ-opioid receptors and compromised by κ-opioid receptors in mice.

Pentazocine is a widely used mixed agonist-antagonist opioid. Previous animal studies have demonstrated that pentazocine-induced antinociception displayed a ceiling effect characterized by biphasic dose response with a increasing and then descending analgesia like a bell-shaped curve. This study attempted to clarify the mechanisms underlying such dose-response relationships. ddY and C57BL/6J mice received subcutaneous injection of saline or pentazocine (3, 10, 30, 56, or 100 mg · kg(-1)), at 120 min after subcutaneous injection of saline, a µ-opioid receptor antagonist clocinnamox mesylate (C-CAM) (5 mg · kg(-1)), a κ-opioid receptor antagonist nor-binaltorphimine (nor-BNI) (10 mg · kg(-1)), or the combination of C-CAM and nor-BNI. The antinociceptive effects of pentazocine were evaluated using tail pressure, hot plate, tail flick, and acetic acid writhing tests. Without pretreatment with an opioid receptor antagonist, the antinociceptive effects of pentazocine exhibited biphasic bell-shaped dose-response curves peaking at 30 mg · kg(-1). C-CAM completely and partly antagonized the antinociception induced by pentazocine at low (3-30 mg · kg(-1)) and high (56-100 mg · kg(-1)) doses, respectively. nor-BNI enhanced the antinociception by pentazocine at high doses and turned the later descending portion of the biphasic dose-response curves into a sigmoid curve. The combination of C-CAM and nor-BNI completely abolished the antinociception by pentazocine at all doses. Our results suggest pentazocine produces antinociception primarily via activation of µ-opioid receptors, but at high doses, this µ-opioid receptor-mediated antinociception is antagonized by concomitant activation of κ-opioid receptors. This provides the first reasonable hypothesis to explain the ceiling effects of pentazocine analgesia characterized by a biphasic dose response.