Objective:To explore the effect of Sugammadex sodium on muscle relaxant recovery and coagulation function after modified radical mastectomy for breast cancer.Methods:A total of 110 patients who underwent modified radical mastectomy in Shanxi Cancer Hospital from May. 2022 to May. 2024 were chosen and separated into two groups according to random number table method, with 55 cases in each group, receiving the same anesthesia scheme. Muscle relaxant was monitored by train-of-four stimulation (TOF) . After surgery, when the TOF count was ≥2, the study group was given Sugammadex sodium, and the control group was given neostigmine + atropine. Operation-related indexes and adverse reactions were recorded; The muscle relaxant residue was analyzed at 5, 15 and 30min after injection of muscle relaxant antagonists; Blood clot formation time (K value) , blood clot formation rate (Angle) , maximum blood clot intensity (MA value) and blood clot reaction time (R value) of the two groups were compared before (T1) and 5min (T2) , 15min (T3) and 30min (T4) after injection.Results:The extubation time and the first extubation time in the study group were shorter [ (4.10±1.05) min, (22.95±2.24) h vs. (13.28±2.96) min, (29.83±3.06) h] ( t=21.68, 13.46, all P < 0.05) . The muscle relaxation residual rates in the study group at 5min and 15min were lower [12.73% (7/55) , 0.00% (0/55) vs. 100.00% (55/55) , 63.64% (35/55) ] ( χ2=85.16, 51.33, P < 0.05) . There were no differences in K value, Angle value, MA value and R value between the two groups at T1, T2, T3 and T4 ( t K=0.17, 0.44, 0.14, 0.13, t Angle=0.93, 1.29, 1.04, 1.00, t MA=1.17, 1.72, 0.87, 1.03, t R=0.36, 0.08, 0.09, 0.37, all P > 0.05) . The incidence rates of postoperative nausea, vomiting and respiratory depression in the study group were lower [5.45% (3/55) , 7.27% (4/55) , 0.00% (0/55) vs. 18.18% (10/55) , 21.82% (12/55) , 10.91% (6/55) ] ( χ2/ Fisher=4.27, 4.68, -, all P < 0.05) . Conclusion:Sugammadex sodium can promote the recovery of muscle relaxant in patients after modified radical mastectomy for breast cancer, and has little effect on coagulation function, which can reduce the occurrence of postoperative adverse reactions.

Objective:To investigate the effects of dexmedetomidine combined with esketamine on postoperative analgesia, immune function and inflammatory response in patients undergoing radical mastectomy.Methods:108 patients with breast cancer who received radical mastectomy in Breast Surgery Department, Shanxi Cancer Hospital from Apr. 2022 to Apr. 2024 were divided into the control group (n=54, esketamine) and the observation group (n=54, esketamine + dexmedetomidine) by random number table method. The postoperative recovery, analgesic effect, immune function indexes and inflammatory factors were compared between the two groups, and the occurrence of adverse reactions were recorded.Results:The number of postoperative analgesic pump compression in the observation group was less than that in the control group ( t = 6.60, P<0.05); There was no significant difference between the two groups in the proportion of patients with additional analgesic drugs, postoperative wakefulness-eye opening time or 15-item quality of recovery (QoR-15) scale ( χ2=0.32, t=1.32, 1.15, P>0.05); The observation group had lower VAS scores at 30min (T1), 4 h (T2), 8 h (T3) and 12 h (T4) after surgery ( t=4.82, 6.53, 14.01, 12.87, P<0.05); At T1, T2, T3 and T4, peripheral helper T cells (Th) 1 and Th1/Th2 in observation group were higher, while Th2 was lower ( t=3.98, 4.62, 4.12, 8.52, 3.81, 9.47, 13.98, 9.53, 4.44, 4.50, 4.31, 5.45, all P<0.05); The observation group had lower tumor necrosis factor -α (TNF-α), interleukin-6 (IL-6) at T1, T2, T3 and T4, while higher IL-2 ( t=2.46, 2.99, 2.29, 3.05, 2.85, 3.64, 4.70, 2.51, 3.17, 3.74, 3.24, 2.79, all P<0.05); The incidence of adverse reactions between the two groups showed no significant difference ( χ2=2.31, P>0.05) . Conclusion:Dexmedetomidine combined with esketamine analgesia regimen can significantly improve the analgesic effect after radical mastectomy, reduce postoperative inflammatory response, and effectively protect postoperative immune function of patients, with certain safety.

Objective:To study the effects of remimazolam on stress response index, T lymphocyte subsets and postoperative delirium in patients undergoing modified radical mastectomy.Methods:A total of 120 patients with breast cancer who underwent modified radical mastectomy in our hospital from Aug. 2024 to Dec. 2024 were separated into the control group (n=60, anesthetic induction and maintenance with Propofol) and the observation group (n=60, anesthetic induction and maintenance with remimazolam) according to random number table method, and the other anesthetic drugs were the same. The operation time, anesthesia recovery time, postoperative delirium and cognitive dysfunction of the two groups were observed, and the changes of stress response indexes and T lymphocyte subsets indexes at different time points were compared, and the adverse reactions after anesthesia were counted.Results:The incidence of postoperative delirium and cognitive dysfunction in the observation group was lower than that in the control group ( x2=4.62, 5.18, P < 0.05), and there was no statistically significant difference in operation time or anesthesia recovery time between the two groups ( t=0.43, 1.71, P > 0.05). The observation group had lower serum cortisol (Cor), norepinephrine (NE) and epinephrine (E) levels 30 min after anesthesia induction (T 1) and immediately after surgery (T 2) ( t=5.53, 6.71, 9.33, 6.74, 7.26, 8.77, P < 0.05), while the comparison of those indexes before surgery (T 0) and 12 h after surgery (T 3) showed no statistically significant difference ( t=1.19, 1.85, 0.90, 1.55, 1.64, 1.81, P > 0.05). The levels of CD3 +T, CD4 +T and CD4 +/CD8 + in the observation group were higher than those in the control group at T 1, T 2 and T 3 ( t=2.21, 4.94, 4.77, 4.44, 6.24, 7.07, 2.11, 2.56, 2.15, P < 0.05), and there was no statistically significant difference in those indexes between the two groups at T 0 ( t=0.76, 0.79, 1.51, P > 0.05). The incidence of adverse reactions after anesthesia showed no statistically significant difference between the two groups [25.00% (15/60) and 33.33% (20/60) ] ( χ2=1.008, P > 0.05) . Conclusion:The induction and maintenance of remimazolam anesthesia can effectively reduce the incidence of postoperative delirium and cognitive dysfunction in patients with modified radical mastectomy, relieve the body stress response of patients, and effectively reduce the influence of anesthesia on T lymphocytes.

Objective:To investigate the application effect of medical failure modes and effects analysis(FMEA)in reducing the inci-dence rate of catheter dislodgement in patients in the post-anesthesia care unit(PACU).Methods:A retrospective study was con-ducted among 469 PACU patients in our hospital from January 2023 to June 2024.According to the application time of FMEA,the pa-tients were divided into routine group(234 PACU patients who did not receive FMEA from January to June 2023)and FMEA group(235 PACU patients who received FMEA from July 2023 to June 2024).The two groups were compared in terms of the incidence rate of catheter dislodgement,risk priority number(RPN)coefficients(including professional knowledge,risk awareness,and intervention guidance),the quality of recovery of consciousness(including the time to complete recovery of consciousness and the length of stay in the PACU),and the degree of satisfaction with nursing(including risk management,nursing services,and nursing techniques).Results:The FMEA group had a significantly lower incidence rate of catheter dislodgement than the routine group[0.43%(1/235)vs.2.99%(7/234),the difference was statistically significant(χ2=4.604,P=0.032)].Compared with the routine group,the FMEA group had significantly lower RPN coefficients of risk awareness t=52.518,professional knowledge t=49.641,and intervention guidancet=61.592(P<0.001).Compared with the routine group,the FMEA group had significantly shorter time to complete recovery t=18.087 of consciousness and length of stay in the PACUt=15.710(P<0.001).The FMEA group had a significantly higher degree of satisfaction with nursing than the routine group in terms of risk management t=19.794,nursing services t=10.825,and nursing techniques t=14.555(P<0.001).Conclusion:The application of FMEA manage-ment in PACU patients can reduce the incidence rates of catheter dislodgement and risk events and improve the quality of recovery of consciousness and the degree of satisfaction with nursing,and there-fore,it has important clinical significance.

Objective:To investigate the expression of interleukin (IL)-22 in lung adenocarcinoma and its effect and possible mechanism for lung adenocarcinoma metastasis.Methods:The cancer tissues and paired adjacent normal tissues (>2 cm from the tumor edge) surgically removed from 27 lung adenocarcinoma patients in Tianjin Medical University Cancer Institute & Hospital from January to June 2023 were retrospectively collected. Flow cytometry was used to detect the expression levels of IL-22 in T cells of all tissues, and the expression levels of IL-22 in T cells were compared between cancer and adjacent tissues, as well as between lung cancer tissues of patients with and without lymph node metastasis. The cancer tissues and paired adjacent normal tissues were retrospectively collected from 6 patients with lung adenocarcinoma during the same period, and the expression level of IL-22 receptor IL-22RA1 in the tissues was detected by Western blotting. IL-22RA1 transcriptome data from cancer tissues of lung adenocarcinoma patients in 3 datasets in The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database were collected. Using the R software survminer package to select the optimal critical value of IL-22RA1 that reflected the survival relationship, and patients were divided into high and low IL-22RA1 groups based on this. The survival package was used to draw the overall survival curve and log-rank test was performed for inter group comparison. Recombinant IL-22 was used to treat human lung adenocarcinoma A549 cells and mouse lung adenocarcinoma LLC cells, with cells not treated with IL-22 as controls; Transwell assay was used to detect the number of migrating cells in each group; Western blotting was used to detect the expression levels of ERK, AKT and STAT signaling pathways-related proteins, matrix metalloproteinase 9 (MMP-9) and epithelial cadherin (E-cad) in each group of cells. The expression levels of these proteins in A549 cells and LLC cells were also measured after the addition of STAT3 inhibitor C188-9, AKT inhibitor MK-2206 and ERK inhibitor SCH772984. A lung metastasis model of LLC cells was constructed using 10 C57BL/6 mice, the mice were randomly divided into the experimental group and the control group using simple randomization method. IL-22 neutralizing antibody (50 μg/mouse) and non-neutralizing control antibody (50 μg/mouse) were injected once every other day. On the 10th day, the mice were euthanized and dissected to count lung metastatic nodules. The metastatic lung tissue was stained with HE and the metastatic foci were counted. Flow cytometry was used to detect the proportion of CD4 + T cells and CD8 + T cells to immune cells in single cells prepared from metastatic lung tissue. Results:The flow cytometry analysis showed that the proportion of IL-22 + CD4 + T cells in T cells (labeled with CD3 and CD45) in 27 clinically collected lung adenocarcinoma tissues [ M ( Q1, Q3)] was higher than that in adjacent normal tissues [0.28% (0.04%, 1.00%) vs. 0.01% (0.00%, 0.25%)]. The proportion of IL-22 + CD4 + T cells in lung adenocarcinoma tissues of patients with metastasis (9 cases) was higher than that of patients without metastasis (18 cases) [1.06% (0.49%, 4.72%) vs. 0.15% (0.00%, 0.35%)], and the differences were statistically significant (both P < 0.01). Western blotting analysis showed that the relative expression level of IL-22RA1 protein in lung adenocarcinoma tissues was higher than that in adjacent normal tissues (1.03±0.25 vs. 0.35±0.10), and the difference was statistically significant ( P < 0.05). The overall survival of the IL-22RA1 low expression group in lung adenocarcinoma tissues was better than that of the IL-22RA1 high expression group in the TCGA database and GEO databases GSE42127, GSE29016 and GSE26939 datasets, and the differences were statistically significant (all P < 0.001). Transwell assay showed that A549 cells [(744±40) cells, (770±64) cells vs. (403±42) cells] and LLC cells [(167±39) cells, (246±80) cells vs. (31±5) cells] treated with 100 and 200 ng/ml IL-22 for 24 hours had fewer migration numbers than the control group, and the differences were statistically significant (both P < 0.01). Western blotting analysis showed that during treatment with 100 ng/ml recombinant IL-22 for 15-1 440 minutes, the levels of p-STAT3, p-ERK and p-AKT proteins in A549 and LLC cells were higher than those in the control group, while there was no difference in the levels of E-cad and MMP-9 proteins between the two groups. After the combined treatment of recombinant IL-22 and STAT3, AKT or ERK inhibitor, the corresponding levels of p-STAT3, p-AKT and p-ERK proteins in A549 and LLC cells were similar to those in cells without inhibitor and recombinant IL-22 treatment, but significantly lower than those in cells treated with recombinant IL-22 alone. In the dissected lung tissues of mice lung metastasis models, the experimental group had fewer metastatic lung nodules than the control group (2.3±0.6 vs. 7.0±2.0), and the difference was statistically significant ( t = 3.88, P = 0.018). In the morphological observation of lung metastasis tissues, the experimental group had fewer metastatic lesions than the control group (1.8±0.8 vs. 5.4±1.1), and the difference was statistically significant ( t = 5.69, P < 0.001). Flow cytometry analysis showed that the proportion of CD8 + T cells in immune cells in the lung tissues of mice in the experimental group (labeled with CD45) was higher than that in the control group [(27±5)% vs. (15±5)%], and the difference was statistically significant ( t = 3.01, P = 0.040). There was no statistically significant difference in the proportion of CD4 + T cells in immune cells between the two groups ( P > 0.05). Conclusions:The expression levels of IL-22 and its receptor IL-22RA1 in lung adenocarcinoma tissues are higher than those in adjacent normal tissues, and the high expression level of IL-22RA1 in cancer tissues may be associated with poor prognosis of patients; on the one hand, IL-22 may promote the migration of lung adenocarcinoma cells by activating the ERK, AKT and STAT3 signaling pathways, and on the other hand, it may promote lung adenocarcinoma metastasis by reducing CD8 + T cell infiltration in the immune microenvironment of lung adenocarcinoma.

Objective:To investigate the effect of different degrees of neuromuscular blockade on postoperative pain of patients receiving laparoscopic radical gastrectomy.Methods:A prospective randomized-controlled study was conducted. A total of 128 patients undergoing laparoscopic radical gastrectomy with American Society Anesthesiologists grade Ⅰ or Ⅱ in Shanxi Province Cancer Hospital from May 2023 to October 2024 were selected, and all patients were randomly divided into deep neuromuscular blockade group (group D, 64 cases) and moderate neuromuscular blockade group (group M, 64 cases) according to the random number table method. The patients in both groups were treated with general intravenous anesthesia combined with transversus abdominis plane block under the monitoring of a train-of-four (TOF) stimulus of the adductor pollicis muscle. The intraoperative pneumoperitoneum pressure was maintained at 12 mmHg (1 mmHg=0.133 kPa). Patient controlled analgesia (PCA) was connected with intravenous analgesia pump after operation. The surgical field exposure scores, the length of operation, anesthetic drug dosage, time of tracheal tube removal (the time from administration of muscle relaxant antagonists until spontaneous breathing returns to normal and the removal time of tracheal tube), time for neuromuscular blockade to recover to a train-of-four stimulus ratio (TOFr) ≥ 0.9, duration of stay in the post-anesthesia care unit (PACU), occurrence of PACU hypoxemia (blood oxygen saturation < 90%) in the PACU, postoperative visual analogue pain score (VAS), occurrence of shoulder pain, total number of presses and effective presses of the analgesic pump were recorded in both groups.Results:There were no statistically significant differences in the baseline data of the 2 groups (all P > 0.05). The surgical field exposure score in group D was higher than that in group M [(4.7±0.5) points vs. (4.0±0.7) points], the total dosage of rocuronium in group D was more than that in the group M [(192±15) mg vs. (141±21) mg], and the differences were statistically significant ( t values were -2.70 and -3.21 respectively, both P < 0.05). There were no significant differences in the time to extubation, the time for neuromuscular blockade recover to TOFr ≥0.9 and the length of stay in PACU, the incidence of hypoxemia in the PACU and the VAS scores at rest and during activity at 1 h and 6 h after surgery between the 2 groups (all P > 0.05). The VAS scores at rest and during activity at 24 h, 48 h and during activity at 72 h after operation in group D were lower than those in group M, and the differences were statistically significant (all P < 0.05). The incidence of shoulder pain after surgery in group D was lower than that in group M [20.0% (9/58) vs. 35.5% (20/58)], and the difference was statistically significant ( χ2 = 5.56, P < 0.05). The total number of postoperative analgesic pump presses and the number of effective presses in group D were less than those in group M, and the differences were statistically significant (both P < 0.05). Conclusions:Laparoscopic radical gastrectomy under deep neuromuscular blockade may alleviate postoperative pain of patients.

Objective:To explore the effect of loneliness on self-perceived aging among elderly patients after gastric cancer surgery, and to examine the mediating role of emotion regulation strategies, in order to provide a basis for clinical interventions.Methods:A convenience sample of 220 elderly postoperative gastric cancer patients hospitalized in Shanxi Provincial Cancer Hospital between August and November 2024 was selected. Data were collected using a general demographic questionnaire, the Emotion Regulation Questionnaire (ERQ), the Cancer Loneliness Scale (CLS), and the Brief Aging Perceptions Questionnaire (B-APQ). A structural equation model was constructed using AMOS 26.0, and the significance of the mediating effect was tested using the bootstrap method with 5 000 resamples.Results:A total of 220 questionnaires were distributed in this study, and 203 valid questionnaires were recovered, with a response rate of 92.27%. The total B-APQ score was (47.45±11.43). For the ERQ, the score for cognitive reappraisal was (22.80±8.17), and for expressive suppression was (18.37±5.10). The CLS score was (18.19±6.11). Mediation analysis showed that loneliness had a direct effect of 0.353 on self-perceived aging. Emotion regulation strategy—cognitive reappraisal—partially mediated the relationship between loneliness and self-perceived aging, with a mediation effect value of 0.178, accounting for 33.52% of the total effect (0.178/0.531) .Conclusions:Clinical practitioners should implement interventions to reduce loneliness in elderly patients after gastric cancer surgery and guide them in adopting cognitive reappraisal as an emotion regulation strategy. These approaches may help promote positive aging in this patient population.

Objective:To investigate the effect of hydrogen on the expressions of stromal interaction molecule 1 (STIM1) and Ca 2+-release-activated-Ca 2+ channel protein 1 (Orai1) and the protective effect of hydrogen on septic mice acute lung injury (ALI). Methods:Forty-eight male ICR mice were divided into sham operation group (Sham group), hydrogen control group (Sham+H 2 group), sepsis group (SS group) and hydrogen intervention group (SS+H 2 group) according to a random number table method, with 12 mice in each group. Sepsis mice model were established by cecal ligation and puncture (CLP). Sham group and Sham+H 2 group did not undergo CLP, other operations were the same as follow. Sham+H 2 group and SS+H 2 group received 1 hour inhalation of 2% H 2 at 1 hour and 6 hours after CLP or sham operation. At 24 hours after CLP, 6 mice in each group were sacrificed for observing pulmonary microvascular permeability after injecting Evans blue (EB) through tail vein. Other 6 mice in each group were sacrificed for obtaining fresh lung tissue to observe the lung pathological change and lung wet/dry (W/D) weight ratio. The protein expressions and distribution of STIM1 and Orai1 in lung tissue were detected by Western blotting and immunofluorescence staining. The mRNA expressions of STIM1 and Orai1 in lung tissue were detected by reverse transcriotion-polymerase chain reaction (RT-PCR). Coimmunoprecipitation was used to observe STIM1-Orai1 interaction. Finally, pulmonary microvascular endothelial cells (PMVEC) of mice were cultured in vitro and randomly divided into four groups for inoculation onto culture plates: Control group, rich hydrogen solution group (Control+H 2 group), lipopolysaccharide (LPS) group and rich hydrogen solution intervention group (LPS+H 2 group). PMVECs in Control group and LPS group were cultured in normal medium. Control+H 2 group and LPS+H 2 group were cultured in saturated hydrogen medium. LPS group and LPS+H 2 group were added with LPS at 5 μg/mL. Intracellular Ca 2+ ([Ca 2+]i) concentration of PMVECs were detected by Fluo-4/AM green dye. Results:Compared with Sham group, the pathological score and lung W/D ratio were significantly increased in SS group at 24 hours after CLP (pathological score: 11.00±1.41 vs. 1.00±0.63, lung W/D ratio: 7.63±0.52 vs. 3.45±0.58, both P < 0.05), the content of EB in the lung tissue was increased (μg/g: 0.16±0.02 vs. 0.09±0.02, P < 0.05). Compared with SS group, the pathological score and lung W/D ratio were decreased in SS+H 2 group (pathological score: 3.50±1.05 vs. 11.00±1.41, lung W/D ratio: 4.45±0.45 vs. 7.63±0.52, both P < 0.05), the content of EB in the lung tissue was decreased (μg/g: 0.13±0.02 vs. 0.16±0.02, P < 0.05), which prove that hydrogen can improve ALI caused by sepsis. Compared with Sham group, the protein and mRNA expressions of STIM1 and Orai1 were up-regulated in SS group (relative expression level of STIM1 protein: 3.08±0.32 vs. 1.00±0.00, relative expression level of STIM1 mRNA: 3.65±0.24 vs. 1.00±0.00, relative expression level of Orai1 protein: 3.63±0.23 vs. 1.00±0.00, relative expression level of Orai1 mRNA: 3.80±0.22 vs. 1.00±0.00, all P < 0.05), while the protein and mRNA expressions of STIM1 and Orai1 were down-regulated in SS+H 2 group compared with SS group (relative expression level of STIM1 protein: 1.78±0.13 vs. 3.08±0.32, relative expression level of STIM1 mRNA: 1.76±0.28 vs. 3.65±0.24, relative expression level of Orai1 protein: 1.92±0.22 vs. 3.63±0.23, relative expression level of Orai1 mRNA: 1.85±0.18 vs. 3.80±0.22, all P < 0.05). Coimmunoprecipitation staining results showed that there was no statistically significance in the association between STIM1 and Orai1 in Sham group and Sham+H 2 group. Compared with Sham group, the STIM1-Orai1 interaction was increased in SS group (relative expression level: 3.71±0.37 vs. 1.00±0.00, P < 0.05), while the STIM1-Orai1 interaction was decreased in SS+H 2 group compared with SS group (relative expression level: 2.17±0.29 vs. 3.71±0.37, P < 0.05). There were no statistically significant differences in various indicators between Sham group and Sham+H 2 group. In vitro, the intracellular [Ca 2+]i concentration in PMVECs was increased in LPS group compared with Control group using Fluo-4/AM green dye. The intracellular [Ca 2+]i concentration in PMVECs was decreased in LPS+H 2 group compared with LPS group. Conclusion:The protective effect of hydrogen on lung tissues in septic mice is related to the inhibition of STIM1, Orai1 and the interaction between them.

Objective:To evaluate the role of spinal Annexin A3 (ANXA3) in neuropathic pain in mice.Methods:Sixty-four SPF healthy adult male C57BL/6 mice, weighing 22-26 g, aged 8-10 weeks, were divided into 4 groups ( n=16 each) by the random number table method: sham operation group (group S), chronic constriction injury (CCI) group, CCI+ negative control adeno-associated virus AAV-NC group (group CCI+ N) and CCI+ adeno-associated virus AAV-shANXA3 group (group CCI+ sh). The neuropathic pain was induced by CCI of the sciatic nerve in anesthetized animals. The AAV-shANXA3 and AAV-NC (5 μl) were intrathecally injected at 14 days before developing the model in CCI+ N group and CCI+ sh group. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before developing the model and at 7, 14 and 21 days after developing the model. All the mice were sacrificed after the last measurement of pain threshold, the L 4-6 segments of the spinal cord were removed for determination of the expression of ANXA3, phosphorylated nuclear factor-kappa B (p-NF-κB) and ionized calcium-binding adaptor molecule-1 (Iba-1)(by Western blot), expression of ANXA3 mRNA (by real-time polymerase chain reaction), microglial activation (using the immunofluorescence staining), and contents of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-6 and anti-inflammatory cytokines transforming growth factor-beta (TGF-β) and IL-10 (using enzyme-linked immunosorbent assay). Results:Compared with group S, the MWT was significantly decreased and TWL was shortened after developing the model, the expression of ANXA3 protein and mRNA, p-NF-κB and Iba-1 in spinal cord was up-regulated, the contents of TNF-α, IL-1β and IL-6 were increased, the contents of TGF-β and IL-10 were decreased ( P<0.05), the activation of microglia in the spinal cord was significantly increased, and the cell body was enlarged in group CCI. There was no significant difference in each parameter between group CCI and group CCI+ N ( P>0.05). Compared with CCI+ N group, the MWT was significantly increased on days 14 and 21 after developing the model, the TWL was prolonged on day 21 after developing the model, the expression of ANXA3 protein and mRNA, p-NF-κB and Iba-1 was down-regulated, the contents of TNF-α, IL-1β and IL-6 were decreased, the contents of TGF-β and IL-10 were increased ( P<0.05), and the activation of spinal microglia was decreased in CCI+ sh group. Conclusions:Spinal ANXA3 may be involved in the development and maintenance of neuropathic pain by activating the NF-κB signaling pathway and further promoting microglial activation in mice.

Objective:To evaluate the role of spinal Annexin A3 (ANXA3) in neuropathic pain in mice.Methods:Sixty-four SPF healthy adult male C57BL/6 mice, weighing 22-26 g, aged 8-10 weeks, were divided into 4 groups ( n=16 each) by the random number table method: sham operation group (group S), chronic constriction injury (CCI) group, CCI+ negative control adeno-associated virus AAV-NC group (group CCI+ N) and CCI+ adeno-associated virus AAV-shANXA3 group (group CCI+ sh). The neuropathic pain was induced by CCI of the sciatic nerve in anesthetized animals. The AAV-shANXA3 and AAV-NC (5 μl) were intrathecally injected at 14 days before developing the model in CCI+ N group and CCI+ sh group. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before developing the model and at 7, 14 and 21 days after developing the model. All the mice were sacrificed after the last measurement of pain threshold, the L 4-6 segments of the spinal cord were removed for determination of the expression of ANXA3, phosphorylated nuclear factor-kappa B (p-NF-κB) and ionized calcium-binding adaptor molecule-1 (Iba-1)(by Western blot), expression of ANXA3 mRNA (by real-time polymerase chain reaction), microglial activation (using the immunofluorescence staining), and contents of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-6 and anti-inflammatory cytokines transforming growth factor-beta (TGF-β) and IL-10 (using enzyme-linked immunosorbent assay). Results:Compared with group S, the MWT was significantly decreased and TWL was shortened after developing the model, the expression of ANXA3 protein and mRNA, p-NF-κB and Iba-1 in spinal cord was up-regulated, the contents of TNF-α, IL-1β and IL-6 were increased, the contents of TGF-β and IL-10 were decreased ( P<0.05), the activation of microglia in the spinal cord was significantly increased, and the cell body was enlarged in group CCI. There was no significant difference in each parameter between group CCI and group CCI+ N ( P>0.05). Compared with CCI+ N group, the MWT was significantly increased on days 14 and 21 after developing the model, the TWL was prolonged on day 21 after developing the model, the expression of ANXA3 protein and mRNA, p-NF-κB and Iba-1 was down-regulated, the contents of TNF-α, IL-1β and IL-6 were decreased, the contents of TGF-β and IL-10 were increased ( P<0.05), and the activation of spinal microglia was decreased in CCI+ sh group. Conclusions:Spinal ANXA3 may be involved in the development and maintenance of neuropathic pain by activating the NF-κB signaling pathway and further promoting microglial activation in mice.