OBJECTIVES: Neuropathic pain (NP) is one of the most common forms of chronic pain, yet current treatment options are limited in effectiveness. Peripheral nerve injury activates spinal microglia, altering their inflammatory response and phagocytic functions, which contributes to the progression of NP. Most current research on NP focuses on microglial inflammation, with relatively little attention to their phagocytic function. Early growth response factor 2 (EGR2) has been shown to regulate microglial phagocytosis, but its specific role in NP remains unclear. This study aims to investigate how EGR2 modulates microglial phagocytosis and its involvement in NP, with the goal of identifying potential therapeutic targets. METHODS: Adult male Sprague-Dawley (SD) rats were used to establish a chronic constriction injury (CCI) model of the sciatic nerve. Pain behaviors were assessed on days 1, 3, 7, 10, and 14 post-surgery to confirm successful model induction. The temporal and spatial expression of EGR2 in the spinal cord was examined using real-time quantitative PCR (RT-qPCR), Western blotting, and immunofluorescence staining. Adeno-associated virus (AAV) was used to overexpress EGR2 in the spinal cord, and behavioral assessments were performed to evaluate the effects of EGR2 modulation of NP. CCI and lipopolysaccharide (LPS) models were established in animals and microglial cell lines, respectively, and changes in phagocytic activity were measured using RT-qPCR and fluorescent latex bead uptake assays. After confirming the involvement of microglial phagocytosis in NP, AAV was used to overexpress EGR2 in both in vivo and in vitro models, and phagocytic activity was further evaluated. Finally, eukaryotic transcriptome sequencing was conducted to screen differentially expressed mRNAs, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses to identify potential downstream effectors of EGR2. RESULTS: The CCI model successfully induced NP. Following CCI, EGR2 expression in the spinal cord was upregulated in parallel with NP development. Overexpression of EGR2 via spinal AAV injection enhanced microglial phagocytic activity and increased pain hypersensitivity in rats. Both animal and cellular models showed that CCI or LPS stimulation enhanced microglial phagocytosis, which was further amplified by EGR2 overexpression. Transcriptomic analysis of spinal cord tissues from CCI rats overexpressing EGR2 revealed upregulation of numerous genes associated with microglial phagocytosis and pain regulation. Among them, Lag3 emerged as a potential downstream target of EGR2. CONCLUSIONS EGR2 contributes to the maintenance of NP by enhancing microglial phagocytosis in the spinal dorsal horn.
Animals ; Microglia/metabolism* ; Phagocytosis/physiology* ; Rats, Sprague-Dawley ; Neuralgia/physiopathology* ; Early Growth Response Protein 2/metabolism* ; Male ; Rats ; Spinal Cord/metabolism* ; Sciatic Nerve/injuries*

【Objective】 To reduce the incidence of postoperative intestinal obstruction, we tried to improve surgical techniques by closing the cavity formed during radical cystectomy + ileal passage (Bricker) via laparoscopy to prevent the formation of abdominal hernia. 【Methods】 During Oct.2018 and Feb.2022, 41 patients were involved (conventional group). After standard laparoscopic radical cystectomy + pelvic lymphadenectomy, the ileum channel was established. The right medial retroperitoneum was sutured to cover the mesothelium and end of the ileum channel under open operation or endoscope. The space between the ureter and mesothelium of the ileum channel was sealed, and the end of the ileum channel and both ureters were externalized. During Feb.2022 and Dec.2022, 15 patients were involved (modified group). The right inner and outer lateral peritoneums below the ileal conduit were sutured to "bottom out" the gap between the ileal conduit and the right abdominal wall in addition to standard procedures. The recovery of intestinal function and incidence of bowel obstruction were compared between the two groups. 【Results】 In the conventional group, the intestinal function recovered within 2 to 6 days after surgery, with a median ventilation time of 3 days. Intestinal obstruction occurred in 3 patients, 2 of whom improved after conservative treatment while 1 underwent surgical exploration after ineffective conservative therapy. There were no significant differences in the time of discharge and ventilation between the two groups, but no intestinal obstruction occurred in the modified group. 【Conclusion】 Peritoneal externalization at the end of ileal passage can reduce the incidence of intra-abdominal hernia and postoperative intestinal obstruction, which is worthy of clinical application.

Studies have shown that bone marrow mesenchymal stem cells (BMSCs) transplantation can restore the sensory and motor function of patients with ischemic stroke. BMSCs transplantation is a promising therapeutic strategy because of its ability to differentiate into neuron-like cells. This article reviews the inducers that promote BMSCs to differentiate into neuron-like cells in vitro.

Objective To investigate the effects of maternal behaviors in the rats with neuropathic pain (NP) on emotions of offspring rats and the relationship with DNA methylation in the amygdala.Methods Forty-eight healthy adult Sprague-Dawley rats (24 males and 24 females),weighing 200-250 g,were used in the study.Twelve female and 12 male rats were randomly selected,and NP was induced by chronic constriction injury (CCI).Each female rat was mated with one male rat at 10 days after CCI.Fortyeight F1 generation rats of maternal rats with NP were randomly divided into 2 groups (n =24 each) using a random number table:NP1 group and NP2 group.Forty-eight F1 generation rats of normal maternal rats were randomly divided into 2 groups (n=24 each) using a random number table:S1 group and S2 group.The F1 generation rats were cross-fed immediately after birth between group NP2 and group S2,and fed by their own mother rats in NP1 and S1 groups.All the offspring rats were fed to 21 days after birth by the maternal rats selected,and separately fed to 30 days after birth,and then subjected to behavioral testing.Retrieving and licking pups were recorded after delivery in maternal rats to evaluate the maternal behaviors.The mechanical and thermal paw withdrawal thresholds were measured in the offspring rats.Elevated plus maze and open field tests were conducted to detect anxiety and depression behaviors in the offspring rats.At 1 day after completion of behavioral testing,the expression of DNA methyltransferase 1 (DNMT1) and DNA methyltransferase 3a and 3b in the amygdala was detected by Western blot analysis.Results Compared with S1 or S2 groups,the latency to lick pups,latency to retrieve pups,and total retrieval time were significantly prolonged,and the total time spent licking pups was significantly shortened in NP1 group or NP2 group (P＜0.05 or 0.01).There was no significant difference in the mechanical and thermal paw withdrawal thresholds in the offspring rats between the four groups (P＞0.05).Compared with group S1,the ratios of time spent in the open arm to the closed arm and of time spent in the central square to the peripheral square were significantly decreased,DNMT1 expression in the amygdala was significantly up-regulated,and the total DNA methylation was increased in the offspring rats in S2 and NP1 groups (P＜0.05).Compared with group NP2,the ratios of time spent in the open arm to the closed arm and of time spent in the central square to the peripheral square were significantly decreased,DNMT1 expression in the amygdala was significantly up-regulated,and the total DNA methylation was increased in the offspring rats in S2 and NP1 groups (P＜0.05).Conclusion Decreased maternal behaviors in the rats with NP results in negative emotions including anxiety and depression in the offspring rats,and the mechanism is related to increased DNA methylation in the amygdala of the offspring rats.

OBJECTIVE: To determine the drug resistance of Comamonas testosteroni (C. testosteroni) by the Kirby-Bauer (K-B) method without Clinical and Laboratory Standards Institute (CLSI) explanation or the minimum inhibitory concentration (MIC) method with the standard CLSI explanation to evaluate the sensitivity of K-B method in detection of C. testosteroni.
 METHODS: K-B method and MIC method was used to determine the sensitivity of C. testosteroni to Piperacillin, Cefepime, Piperacillin/tazobactam, Imipenem, Meropenem, Amikacin, Gentamicin, Tobramycin, Ceftazidime and Ciprofloxacin. The interpretation standard for Pseudomonas aeruginosa was temporary used for the K-B method. The coincident rate was compared between the two methods.
 RESULTS: The complete or partial coincident rate for K-B method and MIC method to detect Piperacillin and Cefepime was 97.4% or 2.6%; the complete coincidence rate to detect Piperacillin/tazobactam, Imipenem and Meropenem was 100%; the complete or partial coincident rate to detect Amikacin, Gentamicin and Tobramycin 94.7% or 5.3%; the complete or partial coincident rate to detect Ceftazidime was 97.4% or 2.6%; the complete or partial coincident rate to detect Ciprofloxacin 86.8% or 10.6%, and the full non-coincidence rate was 2.6%.
 CONCLUSION The results of drug sensitive test from the two methods are highly consistent. We suggest that the microbiology labs do not report the interpretive results for C. testosteroni with K-B method but report the test results.
Anti-Bacterial Agents ; Cefepime ; Cephalosporins ; Comamonas testosteroni ; Imipenem ; Meropenem ; Microbial Sensitivity Tests ; Penicillanic Acid ; analogs & derivatives ; Piperacillin ; Piperacillin, Tazobactam Drug Combination ; Pseudomonas aeruginosa ; Thienamycins

Objective To investigate the value of the bedside index for severity in acute pancreatitis (BISAP),Ranson's,APACHE Ⅱ and computed tomography severity index (CTSI) scoring system in evaluating the severity of acute pancreatitis.Methods The clinical data of 385 patients with acute pancreatitis who were admitted to the Zhongnan Hospital of Wuhan University from 2005 to 2011 were retrospectively analyzed.The values of 4 scoring systems including BISAP,Ranson's,APACHE Ⅱ and CTSI in predicting the incidences of severe acute pancreatitis,local complications and death were investigated by Chi-square test and receiver operating characteristic curv e.Odds ratio (OR) was calculated.The differences of areas under the curves (AUC) were analyzed using the Z test.Results The incidences of severe acute pancreatitis,local complications and mortality of patients with BISAP score ≥ 3 were 64.4％ (56/87),16.1％ (14/87) and 8.0％ (7/87),which were significantly higher than 13.4％ (40/298),6.4％ (19/298) and 0.3 ％ (1/298) of patients with BISAP score ≤ 2 (x2 =93.4,8.1,19.7,P ＜ 0.05).The incidences of severe acute pancreatitis,local complications and mortality of patients with Ranson's score≥3 were 52.7％ (48/91),22.0％ (20/91) and 7.7％ (7/91),which were significantly higher than 16.3％ (48/294),4.4％ (13/294) and 0.3％ (1/294) of patients with Ranson's score ≤2 (x2 =49.2,27.3,18.5,P ＜0.05).The incidences of severe acute pancreatitis,local complications and mortality of patients with APACHE Ⅱ score ≥ 8 were 46.6％ (27/58),20.7％ (12/58) and 8.6％ (5/58),which were significantly higher than 21.1％ (69/327),6.4％ (21/327) and 0.9％ (3/327) of patients with APACHE Ⅱ score≤7 (x2 =17.0,12.8,14.4,P ＜0.05).The incidences of severe acute pancreatitis,local complications and mortality of patients with CTSI score ≥4 were 51.4％ (19/37),51.4％ (19/37),16.2％ (6/37),which were significantly higher than 22.2％ (77/347),4.0％ (14/347),0.6％ (2/347) of patients with CTSI score≤3 (x2 =15.1,95.3,40.1,P ＜ 0.05).The sensitivity,specificity,positive and negative predictive values of BISAP were 58％,89％,64％,86％,respectively,and the AUC was 0.848,which were significantly higher than the other 3 systems (Z =2.02,4.22,4.78,P ＜ 0.05).The sensitivity,specificity,positive and negative predictive values of CTSI were 58％,95％,51％ and 96％,respectively,and the AUC was 0.926,which was significantly higher than the other 3 systems (Z =3.99,3.24,4.06,P ＜ 0.05).The sensitivity,specificity,positive and negative predictive values of BISAP were 88％,79％,8％ and 100％,respectively,and the AUC was 0.855,with no significant difference compared with the other 3 systems (Z =0.81,0.03,0.14,P ＞ 0.05).Conclusions The accurate rate of BISAP in predicting the severe acute pancreatitis is higher than Ranson's,APACHE Ⅱ and CTSI.The accurate rate of CTSI in predicting the incidence of local complications is higher than the other 3 systems.There is no significant difference of the 4 systems in predicting the mortality.The BISAP scoring system is helpful in early diagnosis of severe acute pancreatitis,and making the individualized treatment plan,thus improving the prognosis of patients.

Objective To evaluate the changes in the expression of acetylated histone H3 (Ac-H3) and deacetylase silent information regulator 1 (SIRT1) in dorsal root ganglions in a rat model of negative phenotype neuropathic pain.Methods Forty-eight male Sprague-Dawley rats,weighing 250-300 g,were randomly divided into 2 groups (n =24 each):sham operation group (group S) and C-fiber dysfunction group (group CFD).The rats were anesthetized with 10％ chloral hydrate 3 ml/kg.C-fiber dysfunction was induced by exposing sciatic nerve to 8％ capsaicin for 30 min in group CFD.The thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) were measured before and on 1,3,7 and 14 days after CFD.Six rats were then sacrificed at each time and the lumbar segments (L5) of the dorsal root ganglions were removed for detection of SIRT1 mRNA expression (by RT-PCR) and Ac-H3 and SIRT1 protein expression (by Western blot).Results Compared with group S,TWL was significantly increased at 1,3,7 and 14 days after CFD,SIRT1 mRNA and protein expression was up-regulated and Ac-H3 expression was down-regulated at 3,7 and 14 days after CFD (P ＜ 0.05),while no significant change was found in MWT at each time point in group CFD (P ＞ 0.05).Conclusion The mechanism of negative phenotype neuropathic pain is related to up-regulation of deacetylase SIRT1 expression and decreased acetylation of histone H3 in rat dorsal root ganglions.