Objective:To investigate whether ferroptosis of nerve cells exists in a rat model of neuropathic pain (NP), and to explore the mechanism of O 3 treatment of NP. Methods:Sixty male SD rats were randomly divided into three groups: neuropathic pain model group (NP group), sham operation group (Sham group) and ozone group (O 3 group). The partial sciatic nerve ligation was used in the NP and O 3 groups to construct a neuropathic pain model. The Sham group was subjected to sham surgery. In the O 3 group, 15 μl of O 3 (40 μg/ml) was injected locally at the injury site, and the NP and Sham were injected with the same amount of air, once per day. The mechanical contraction response threshold (MWT) and thermal contraction latency (TWL) of the rats were measured 1 day before the surgery (T0) and 1, 3, 7, 14 days after the surgery (T1 to T4). The spinal cord segments of rats were collected. The expression levels of glutathione peroxidase 4 (GPX4) and long chain fatty acid coenzyme A synthetase 4 (ACSL4) at T1 to T4 was detected using Western Blot. The number of NeuN+ neuron cells in the spinal dorsal horn at T4 was detected using immunofluorescence technology. The specific changes of ferroptosis at T4 was observed by a transmission electron microscopy. Iron deposition in the spinal dorsal horn at T1 to T4 was measured using ferroptosis kits. Results:Compared with the Sham group, rats in the NP group and O 3 group showed decreasing of MWT decreased and shortening of TWL at T2 to T4, decreasing of NeuN+ neurons in spinal dorsal horn at T4, specific changes of ferroptosis in mitochondria at T4, and increasing of iron content in nerve tissue at T2 to T4. Compared with the Sham group, rats in NP group showed decreasing of GPX4 level and increasing of ACSL4 level. Compared with the NP group, rats in the O 3 group showed increasing of MWT and prolonging of TWL at T2 to T4, increasing of the GPX4 level and decreasing of ACSL4 level at T2 to T4, increasing of the number of NeuN+ neuron cells in the spinal dorsal horn, improving of the mitochondrial atrophy of nerve cells, and decreasing of the iron content in nerve tissue at T2 to T4. The above results are statistically significant (all P<0.05). Conclusions:The mechanism of O 3 in treating neuropathic pain may be through inhibition of iron death.

Objective:To evaluate the reliability and validity of Chinese version of Ureteral Stent-Related Symptom Questionnaire (USSQ) so as to provide a scientific tool for the symptom assessment of patients with indwelling ureteral stents.Methods:Following the translation principle of Brislin, the cultural adjustment of the questionnaire was completed according to the process of literal translation of the scale, back translation, expert committee discussion and pre-experiment, and the Chinese version of USSQ was formed. Inpatients with ureteral stents in the Urology Departments of 3 ClassⅢ Grade A hospitals in Urumqi from April 2018 to February 2019 were selected as research objects, and 485 questionnaires were collected by analyzing and testing the items and reliability and validity of the questionnaire.Results:Finally, 462 valid questionnaires were collected. The analysis results of the project suggested that the two items of S1 and S2 in the Chinese version of USSQ in the field of sexual life could be deleted ( P>0.05) , however, considering the rationality of the structure of the questionnaire, S1 should be retained. Cronbach's α coefficient of the questionnaire was 0.923, Cronbach's α coefficient of the six dimensions of urinary symptoms, physical pain, total health status, work performance, sexual life and additional problems was 0.703 to 0.918, retest reliability was 0.885, retest correlation coefficient of the six dimensions was 0.338 to 0.849 ( P<0.05) , and half reliability was 0.628. The content validity of the questionnaire was 0.887. Through exploratory factor analysis, the cumulative variance contribution rate of the nine principal factors was 68.995%. In the correlation analysis, except for the correlation coefficients in the field of sexual life and other fields were from 0.014 to 0.101 ( P>0.05) , the correlation coefficients in other dimensions were from 0.406 to 0.629 ( P<0.01) . The test results of criterion validity showed that the correlation coefficients of each dimension of the questionnaire with International Prostate Symptom Score (IPSS) , Incontinence Quality of Life Scale (I-QOL) and The 12-Item Short Form Health Survey (SF-12) were from 0.35 to 0.49 ( P<0.01) . Conclusions:In addition to the field of sexual life, the Chinese version of USSQ has good reliability and validity in the evaluation of symptoms in other fields, which can provide a basis for the investigation and improvement of related symptoms in patients with indwelling ureteral stents in China.

Objective To compare the analgesic effect and the effect on the success rate of reduc-tion of three doses of remifentanil combined with dexmedetomidine in the clamping reduction of cricoarytenoid joint dislocation.Methods Fifty-one patients with cricoarytenoid joint dislocation,30 males and 21 females,aged 18-80 years,BMI 18.5-30.0 kg/m2,ASA physical status Ⅰ-Ⅲ,were selected from April 2021 to December 2022 in the department of otolaryngology,head and neck surgery.The patients were randomly divided into three groups according to remifentanil dose:remifentanil 0.5 μg·kg-1·min-1 group(group A,n=17),remifentanil 1.0 μg·kg-1·min-1 group(group B,n=18),and remifentanil 1.5 μg·kg-1·min-1 group(group C,n=16).After admission,dexmedetomidine 0.6 μg·kg 1·h-1 was injected intravenously,and an ear,nose and throat anesthetic spray(2％lidocaine 2 ml)was used to administer surface anesthesia to the base of the tongue.A second surface anesthesia was administered to the throat at 5 minutes,and dexmedetomidine was stopped at 10 minutes.The supraglottic and periarticular cri-coarytenoid joints were subjected to superficial anesthesia for a third time under visual laryngoscope,and then remifentanil at corresponding doses was injected intravenously in three groups for 5 minutes,and the reduction operation began after the pumping was stopped.The success of the first reduction,the anesthesia quality satisfaction score of the surgeon and the recovery of remifentanil during the operation were recorded.VAS pain scores were recorded at the time of entry,3 minutes,30 minutes,and 6 hours after operation.The adverse reactions during operation and recovery were recorded.Results Compared with group B,the success rate of first reduction and the score of anesthesia quality satisfaction were significantly decreased in groups A and C(P＜0.05).Compared with group A,the ratio of additional remifentanil supplementation in groups B and C was significantly reduced,and the VAS pain score 3 minutes after surgery was significant-ly decreased(P＜0.05).Compared with group C,the proportion of mandibular manipulation ventilation in groups A and B was significantly reduced(P＜0.05).There was no significant difference in the incidence of bradyheart rate,nausea and vomiting,agitation,delirium and laryngeal spasm between the three groups.Conclusion Compared with remifentanil 0.5 and 1.5 μg·kg-1·min-1,remifentanil 1.0 μg·kg-1·min-1 combined with dexmedetomide sequential pumping provided good analgesic effect for the clamping reduction of cricoarytenoid joint dislocation,improved the success rate of the first reduction,more stable respiratory circulation and fewer perioperative adverse reactions.

Endoplasmic reticulum (ER) stress is mediated by disturbance of Ca²⁺ homeostasis. The store-operated calcium (SOC) channel is the primary Ca²⁺ channel in non-excitable cells, but its participation in agent-induced ER stress is not clear. In this study, the effects of tunicamycin on Ca²⁺ influx in human umbilical vein endothelial cells (HUVECs) were observed with the fluorescent probe Fluo-4 AM. The effect of tunicamycin on the expression of the unfolded protein response (UPR)-related proteins BiP and CHOP was assayed by western blotting with or without inhibition of Orai1. Tunicamycin induced endothelial dysfunction by activating ER stress. Orai1 expression and the influx of extracellular Ca²⁺ in HUVECs were both upregulated during ER stress. The SOC channel inhibitor SKF96365 reversed tunicamycin-induced endothelial cell dysfunction by inhibiting ER stress. Regulation of tunicamycin-induced ER stress by Orai1 indicates that modification of Orai1 activity may have therapeutic value for conditions with ER stress-induced endothelial dysfunction.
Blotting, Western ; Calcium ; Endoplasmic Reticulum ; Endoplasmic Reticulum Stress ; Endothelial Cells ; Homeostasis ; Human Umbilical Vein Endothelial Cells ; Tunicamycin ; Unfolded Protein Response

Depression is a mental disorder with high morbidity, disability and relapse rates. Ginkgo biloba extract (GBE), a traditional Chinese medicine, has a long history of clinical application in the treatment of cerebral and mental disorders, but the key mechanism remains incompletely understood. Here we showed that GEB exerted anti-depressant effect in mice through regulating gut microbial metabolism. GBE protected against unpredictable mild stress (UMS)-induced despair, anxiety-like and social avoidance behavior in mice without sufficient brain distribution. Fecal microbiome transplantation transmitted, while antibiotic cocktail abrogated the protective effect of GBE. Spatiotemporal bacterial profiling and metabolomics assay revealed a potential involvement of Parasutterella excrementihominis and the bile acid metabolite ursodeoxycholic acid (UDCA) in the effect of GBE. UDCA administration induced depression-like behavior in mice. Together, these findings suggest that GBE acts on gut microbiome-modulated bile acid metabolism to alleviate stress-induced depression.
Humans ; Mice ; Animals ; Depression/drug therapy* ; Gastrointestinal Microbiome ; Plant Extracts ; Ginkgo biloba