Local anesthetics (LAs), such as articaine (AT), exhibit limited efficacy in inflammatory environments, which constitutes a significant limitation in their clinical application within oral medicine. In our prior research, we developed AT-17, which demonstrated effective properties in chronic inflammatory conditions and appears to function as a novel oral LA that could address this challenge. In the present study, we further elucidated the beneficial effects of AT-17 in acute inflammation, particularly in oral acute inflammation, where mitochondrial-related apoptosis played a crucial role. Our findings indicated that AT-17 effectively inhibited lipopolysaccharide (LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction in vitro. This process involved the inhibition of mitochondrial reactive oxygen species (mtROS) production and the subsequent activation of the NRF2 pathway. Most notably, improvements in mitochondria-related apoptosis were key contributors to AT-17's inhibition of voltage-gated sodium channels. Additionally, AT-17 was shown to reduce mtROS production in nerve cells through the Na⁺/NCLX/ETC signaling axis. In conclusion, we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis. This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.

Objective:To evaluate the effect of esketamine combined with ultrasound-guided dorsal penile nerve block (DPNB) on negative postoperative behavioral changes (NPOBCs) in pediatric patients undergoing circumcision under general anesthesia.Methods:One-hundred and ninety-five pediatric patients, aged 4-8 yr, with body mass index of 10-35 kg, of American Society of Anesthesiologists Physical Status classificationⅠ or Ⅱ, undergoing elective circumcision under general anesthesia, were selected and divided into 3 groups ( n=65 each) using a random number table method: esketamine group (group E), DPNB group (group D) and esketamine combined with DPNB group (group ED). Propofol 1.5 mg/kg was intravenously injected, and the patients were admitted to the operating room after consciousness disappeared in the 3 groups. Esketamine 0.5 mg/kg was intravenously injected in E and ED groups, and the equal volume of normal saline was given in group D. D and ED groups underwent bilateral DPNB with 0.25 % ropivacaine 0.15 ml/kg under ultrasound guidance, with the maximum total amount of the drug not exceeding 10 ml. Fentanyl 1.0 μg/kg and propofol 2.0 mg/kg were intravenously injected prior to the skin incision in the three groups. If intraoperative body movement occurred, propofol 10 mg was added, which could be repeated. The occurrence of intraoperative body movement, respiratory depression and amount of propofol added was recorded. When postoperative pain (FLACC score >4) occurred, flurbiprofen 1 mg/kg was intravenously injected for analgesia, and the usage of flurbiprofen was recorded. When emergence agitation(PEAD score>10) occurred, propofol 1 mg/kg was intravenously injected for sedation, and the occurrence of emergence agitation was recorded. Parents were followed up by telephone at 1, 7 and 30 days postoperatively to assess the occurrence of NPOBCs using the PHBQ scale. Results:Fifty-six patients in group E and 59 patients in D and ED groups finally completed the study.Compared with group E, the incidence of intraoperative body movement was significantly decreased, the amount of additional propofol was reduced, the emergence agitation score, incidence of emergence agitation and severe agitation and usage rate of postoperative flurbiprofen were decreased, and the incidence of separation anxiety at 7 and 30 days postoperatively was decreased in D and ED groups, and the incidence of intraoperative respiratory depression was significantly decreased, and the incidence of NPOBCs at 7 and 30 days postoperatively was decreased in group ED ( P<0.05). Compared with group D, the incidence of intraoperative respiratory depression was significantly decreased, the amount of additional propofol was decreased, the usage rate of postoperative flurbiprofen and incidence of sleep anxiety at 1 day postoperatively were decreased ( P<0.05), and no significant change was found in the incidence of NPOBCs at each time point after operation in group ED ( P>0.05). Conclusions:Esketamine combined with ultrasound-guided DPNB can reduce the occurrence of NPOBCs in pediatric patients undergoing circumcision under general anesthesia.

Objective To investgate the value of various parameters obtained from monoexponential, biexponential, and stretched exponential diffusion?weighted imaging models in the differential diagnosis of breast lesions. Methods A retrospective study performed in 54 patients with pathologically confirmed malignant tumors(n=30), benign lesions(n=34) and normal fibroglandular tissues (n=30). All patients underwent T1WI, T2WI, dynamic enhancement and diffusion weighted MRI with multi?b values at a 3.0 T magnetic resonance imaging unit. All parameters were measured at a workstation. ADC was calculated by using monoexponential analysis(b=0, 800 s/mm2). Slow apparent diffusion coefficient (ADC?slow), fast apparent diffusion coefficient (ADC?fast), and perfusion fraction (f) were calculated using the biexponential model. Distributed diffusion coefficient (DDC) and water molecular diffusion heterogeneity index (α) were obtained from diffusion?weighted images using the stretched exponential model. All parameters were statistically compared among normal fibroglandular tissues, benign lesions and malignant tumors using Kruskal?Wallis rank sum test. Mann?Whitney U test were used for further comparisons between specific group pairs. ADC values were compared with ADC?slow and DDC for different groups by paired Wilcoxon test. Correlations between ADC?value, ADC?slow and DDC were assessed by using Spearman rank correlation coefficient. Receiver operating characteristic curve was used to analyze and compare the ability of these parameters in differentiation of benign and malignant breast lesions. Results The ADC, ADC?slow, f, DDC and α values were significantly different among the normal fibroglandular tissues, benign tumors and malignant tumors (P<0.05). Further differential comparisons of the four parameters between each pair showed that the ADC, ADC?slow, f, DDC and α values were significantly lower in malignant tumors than both in normal fibroglandular tissues and benign tumors(P<0.016 7). The ADC values of normal fibroglandular tissues, benign tumors and malignant tumors were significantly higher than ADC?slow and DDC (P<0.05). The f and DDC had higher area under the receiver operating characteristic curve (0.688 and 0.657 respectively). The optimal cutoff values for ADC, ADC?slow, f, DDC and α were 1.235 × 10-3mm2/s, 0.428 × 10-3mm2/s, 57.8%, 1.175 × 10-3mm2/s and 0.721, respectively. Theαvalue showed higher specificity (65.5%) and the f value had higher sensitivity (82.9%). Conclusion The parameters derived from biexponential and stretched exponential DWI could be helpful for differentiation between benign and malignant breast tumors.