Dexmedetomidine Ameliorate CLP-Induced Rat Intestinal Injury via Inhibition of Inflammation.

The aim was to verify that dexmedetomidine (DEX) can attenuate CLP-induced intestinal injury via inhibition of inflammation. Male Sprague-Dawley (SD) rats were randomly allocated into Sham group and the other three CLP model groups, in terms of different treatments: placebo, DEX, and yohimbine plus DEX (DEX + YOH) groups. Pathology examination was conducted with HE stain. To identify differences among groups, the levels of DAO, and D-lactate in serum were measured by spectrophotometry, and the levels of TNF-α, IL-1ß, and IL-6 in serum and organ were measured by ELISA. The expressions of occludin and TLR4 in tissue were detected by Western blot. The survival rate of an additional group of animals within 7 d was recorded. In DEX group, mortality was lower, histology change was minor, DAO, and D-lactate levels were reduced, and occludin expression was increased; the expressions of TNF-α, IL-1ß, IL-6, and TLR4 were also decreased in DEX group. These results indicated that acute intestinal injury induced by CLP was mitigated by DEX treatment. However, these effects of DEX were significantly attenuated by yohimbine in DEX + YOH group. Our study indicated the protective effects of DEX on CLP-induced injury, which may be associated with the inhibition of inflammation via modulating TLR4 pathway and can be blocked by yohimbine.

Focus on the cGAS-STING Signaling Pathway in Sepsis and Its Inflammatory Regulatory Effects.

Sepsis is a severe systemic inflammatory response commonly occurring in infectious diseases, caused by infection with virulent pathogens. In the pathogenesis of sepsis, the cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase-stimulator of interferon genes (cGAS-STING) signaling pathway serves a crucial role as a fundamental immunoregulatory mechanism. This signaling pathway activates STING upon recognizing intracellular DNA damage and pathogen-derived DNA, subsequently inducing the production of numerous inflammatory mediators, including interferon and inflammatory cytokines, which in turn trigger an inflammatory response. The aim of this paper is to explore the activation mechanism of the cGAS-STING signaling pathway in sepsis and its impact on inflammatory regulation. By delving into the mechanism of action of the cGAS-STING signaling pathway in sepsis, we aim to identify new therapeutic strategies for the treatment and prevention of sepsis.

Perioperative Adjunctive Esketamine for Postpartum Depression Among Women Undergoing Elective Cesarean Delivery: A Randomized Clinical Trial.

Importance: Postpartum depression (PPD) is one of the most common mental health conditions during the perinatal and postpartum periods, which can have adverse effects on both mother and infant. Objective: To investigate the efficacy of perioperative adjunctive esketamine administration after cesarean deliveries in the prevention of PPD. Design, Setting, and Participants: A single-center, double-blind, placebo-controlled, randomized clinical trial was conducted from January 1, 2022, to January 1, 2023, at Fujian Provincial Hospital among 298 women aged 18 to 40 years, with an American Society of Anesthesiologists grade I to III classification and singleton full-term pregnancies who were scheduled for elective cesarean deliveries. Primary analyses were performed on a modified intention-to-treat basis. Interventions: Patients were randomly assigned to the esketamine (n = 148) and control (n = 150) groups. Those in the esketamine group received a single intravenous injection of 0.25 mg/kg of esketamine immediately after fetal delivery, followed by 50 mg of esketamine as an adjuvant in patient-controlled intravenous analgesia for 48 hours after surgery. Saline was given to the control group of patients. Main Outcomes and Measures: The primary outcome was assessments of PPD symptoms by using the Edinburgh Postnatal Depression Scale (EPDS) at postpartum day 7. Positive screening for PPD was defined as a score of 10 or more points on the EPDS. In addition, the EPDS was analyzed as a continuous variable to evaluate depressive symptoms. Secondary outcomes included the Numeric Rating Scale (NRS) of postoperative pain, along with safety evaluations including adverse events and clinical assessments at postpartum days 14, 28, and 42. Results: A total of 298 pregnant women were included, with 150 in the control group (median age, 31.0 years [IQR, 29.0-34.0 years]) and 148 in the esketamine group (median age, 31.0 years [IQR, 28.0-34.0 years]). The prevalence of depression symptoms was significantly lower among patients given esketamine compared with controls (23.0% [34 of 148] vs 35.3% [53 of 150]; odds ratio, 0.55; 95% CI, 0.33-0.91; P = .02) on postpartum day 7. In addition, the esketamine group also showed a significantly lower change in EPDS scores (difference of least-squares means [SE], -1.17 [0.44]; 95% CI, -2.04 to -0.31; effect size, 0.74; P = .008). However, there were no differences between the groups in the incidence of positive screening results for PPD or in changes from the baseline EPDS scores at postpartum days 14, 28, and 42. There were no differences in NRS scores at rest and on movement except on movement at 72 hours postoperatively, when scores were significantly lower in the esketamine group (median, 3.0 [IQR, 2.0-3.0] vs 3.0 [IQR, 3.0-3.5]; median difference, 0 [95% CI, 0-0]; P = .03). Conclusions and Relevance: These results suggest that intravenous administration of esketamine during the perioperative period of elective cesarean delivery can improve depression symptoms during the early postpartum period. However, this antidepression effect may not be universally applicable to patients with low EPDS scores. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2100054199.

Establishment of ultrasound-guided stellate ganglion block in rats.

Background: A novel protocol for accurate stellate ganglion block under ultrasound guidance was designed in rats. This technique raises the success rate of stellate ganglion block and reduces the incidence of brachial plexus and vagus nerve block. Methods: Fifty-six Sprague-Dawley were randomly divided into an ultrasound-guided group (n = 28) and a blind technique group (n = 28). The rats in the blind technique group were injected with 1.5% lidocaine mixed with methylene blue after signs of brachial plexus stimulation were elicited. The lateral side of the cephalic brachial vein was located under the first rib, where lidocaine was injected into the rats in the ultrasound-guided group. The up-and-down sequential method of Dixon was used to determine the minimum effective volume for stellate ganglion block in rats. Furthermore, we calculated the required operative duration of the two methods and observed the difference in the lidocaine diffusion range between the two groups. Results: The minimum effective volume for stellate ganglion block in the ultrasound-guided group was 0.040 ml, and the 95% CI was 0.026-0.052 ml. In the blind technique group, the minimum effective volume was 0.639 ml, and the 95% CI was 0.490-0.733 ml. Within the 95% CI of the lowest effective volume, the incidence of brachial plexus block as a complication of stellate ganglion block under ultrasound guidance was 10.00%. Conclusion: Stellate ganglion block under ultrasound guidance is more accurate than blind detection, which the incidence of complications of stellate ganglion block under ultrasound guidance was significantly lower than under blind detection; the rate of methylene blue staining in the vagus nerve was significantly lower under ultrasound guidance.

S100A9 Upregulation Contributes to Learning and Memory Impairments by Promoting Microglia M1 Polarization in Sepsis Survivor Mice.

Sepsis-associated encephalopathy (SAE) is a clinical syndrome of brain dysfunction secondary to sepsis, which is characterized by long-term neurocognitive deficits such as memory, attention, and executive dysfunction. However, the mechanisms underlying SAE remain unclear. By using transcriptome sequencing approach, we showed that hippocampal S100A9 was significantly increased in sepsis induced by cecal ligation and puncture (CLP) or lipopolysaccharide (LPS) challenge. Thus, we used S100A9 inhibitor Paquinimod to study the role of S100A9 in cognitive impairments in CLP-induced and LPS-induced mice models of SAE. Sepsis survivor mice underwent behavioral tests or the hippocampal tissues subjected to Western blotting, real-time quantitative PCR, and immunohistochemistry. Our results showed that CLP-induced and LPS-induced memory impairments were accompanied with increased expressions of hippocampal microglia Iba1 and CD86 (M1 markers), but reduced expression of Arg1 (M2 marker). Notably, S100A9 inhibition significantly improved the survival rate and learning and memory impairments in sepsis survivors, with a shift from M1 to M2 phenotype. Taken together, our study suggests that S100A9 upregulation might contribute to learning and memory impairments by promoting microglia M1 polarization in sepsis survivors, whereas S100A9 inhibition might provide a potential therapeutic target for SAE.

Transcutaneous Electrical Acupoint Stimulation Improves the Postoperative Quality of Recovery and Analgesia after Gynecological Laparoscopic Surgery: A Randomized Controlled Trial.

Background. We conducted this prospective, randomized, double-blind, placebo-controlled study to evaluate the effects of transcutaneous electric acupoint stimulation (TEAS) on the quality of recovery (QoR) and postoperative analgesia after gynecological laparoscopic surgery. Methods. 74 American Society of Anesthesiologists physical status (ASA) I or II patients undergoing gynecological laparoscopic surgery were randomly allocated to TEAS or control groups. The primary outcome was the quality of recovery, which was assessed on the day before surgery and 24 h after surgery using a 40-item questionnaire. Secondary outcomes included postoperative pain scores, the incidence of postoperative nausea and vomiting (PONV), duration of postanesthesia care unit (PACU) stay, and patient's satisfaction. Results. The TEAS group had higher QoR scores than control group upon 24 h after surgery (177 versus 165; P < 0.001). Compared with the control group, postoperative pain scores and the cumulative number of opioids administered were lower in the TEAS group patients (P = 0.04). TEAS reduced the incidence of PONV and dizziness, as well as duration of PACU stay. Simultaneously, the patient's satisfaction scores were higher in the TEAS group (P = 0.002). Conclusion. Preoperative TEAS enhances QoR, improves postoperative analgesia and patient's satisfaction, alleviates postoperative side effects, and accelerates discharge after general anesthesia for gynecological laparoscopic surgery.

Transcutaneous electric acupoint stimulation alleviates remifentanil-induced hyperalgesia in patients undergoing thyroidectomy: a randomized controlled trial.

BACKGROUND: In this prospective, randomized, double-blind study, we verified the hypothesis that TEAS can alleviate remifentanil-induced hyperalgesia in patients undergoing thyroidectomy. METHODS: 60 American Society of Anesthesiologists physical status (ASA) I-IIpatients, aged 18-60 year, scheduled for thyroidectomy were randomly allocated to TEAS or sham groups. TEAS consisted of 30 min of stimulation (6-9 mA, 2/10 Hz) on the Hegu (LI4) and Neiguan (PC6) before anesthesia. Anesthesia was maintained with sevoflurane adjusted to bispectral index (40-60) and target remifentanil 5.0 ng/ml. Mechanical pain thresholds were assessed using electronic von Frey. The primary outcome was mechanical pain thresholds. Secondary outcomes included postoperative pain scores, the time to first rescue analgesic, cumulative number of rescue analgesia, and side effects, including postoperative nausea and vomiting (PONV), dizziness and shivering in 24 h postoperatively. RESULTS: Baseline mechanical pain thresholds were similar between the groups. The analysis revealed the decrease in mechanical threshold was greater in the sham group than the TEAS group (P < 0.001). Postoperative pain scores and cumulative number of rescue analgesia were lower in the TEAS group (P < 0.05). In addition, TEAS group patients reduced the incidence of PONV and shivering. CONCLUSION: Preoperative TEAS can attenuate remifentanil-induced hyperalgesia in patients undergoing thyroidectomy.

Transcutaneous electric acupoint stimulation at Jiaji points reduce abdominal pain after colonoscopy: a randomized controlled trial.

BACKGROUND: Transcutaneous electric acupoint stimulation (TEAS) at Jiaji acupuncture points has therapeutic potential for relieving viscera pain and opioid-related side effects. This prospective, randomized, triple-blinded, placebo-controlled trial was to investigate the efficacy of TEAS on abdominal pain after colonoscopy. METHODS: Consecutive outpatients with American Society of Anesthesiologists (ASA) physical status I or II underwent selective colonoscopy were randomly assigned into two groups for either TEAS or sham pretreatment. The primary outcomes were the incidence of abdominal pain after colonoscopy. The secondary outcomes included the incidence of abdominal distension, postoperative nausea and vomiting (PONV), duration of PACU stay, and patient's satisfaction and acceptance. RESULTS: Among the 229 patients analyzed, fewer occurrence of post-procedural abdominal pain (11.4% vs 25.2%, P = 0.007) and distension (1.8% vs 7.8%, P = 0.032) were observed in TEAS group, when compared with the sham group. The duration of PACU stay was significant shortened in TEAS group (P < 0.001). Meanwhile, patients' satisfaction score to medical service was higher (P < 0.001), and their acceptance to colonoscopy was improved (P = 0.011). CONCLUSION: Pretreatment with TEAS can reduce post-procedural discomfort, provide more efficient medical resources utilization, and improved patient's satisfaction and colonoscopy acceptance.