Objective To study the effect of STAT3 over-expression-mediated A2 astrocyte polarization on type 1 diabetic mellitus(T1DM)peripheral neuropathy.Methods STAT3 over-expression virus was intrathecally injected into type 1 diabetic rats with painful diabetic neuropathy(PDN).The rats were divided into four groups:control group,T1DM group,T1DM+vector group,and T1DM+STAT3 OE group.Paw withdrawal threshold and paw withdrawal latency were measured.Flow cytometry and RT-qPCR were used to sort astrocytes and determine the phenotype of reactive astrocytes.Immune-fluorescence staining microscopy was performed to observe the changes of A2 phenotype astrocytes in the spinal dorsal horn of each group.Results Compared to the control group,the me-chanical(P＜0.001)and heat thresholds(P＜0.05)were significantly reduced in the T1DM group.The mechanical threshold was significantly increased in the T1DM+STAT3 OE group as compared to that in the T1DM group(P＜0.001).Histolgical analysis showed degenerative pathological changes of spinal dorsal horn astrocytes in the T1DM group.Astrocytes in the T1DM+STAT3 OE group were activated and polarized toward the A2 phenotype.Conclusions The STAT3 pathway in the spinal dorsal horn astrocytes of rats with type 1 diabetic neuropathy is im-paired.Restoring STAT3 expression promotes activation of astrocyte proliferation,activation,and polarization toward the A2 phenotype,thereby alleviating diabetic neuropathic pain.

Objective To evaluate the effect of different approaches to thoracolumbar interfascial plane (TLIP) block on the analgesic efficacy after lumbar spinal fusion.Methods Seventy-five patients of both sexes,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,aged 40-70 yr,with body mass index ≤40 kg/m2,undergoing posterior median approach to lumbar spinal fusion,were divided into 3 groups (n =25 each) using a random number table method:patient-controlled intravenous analgesia (PCIA) group (group P),medial approach to TLIP combined with PCIA group (group MP) and lateral approach to TLIP combined with PCIA group (group LP).TLIP block was performed by advancing the block needle in a lateral to medial direction and injecting 0.5％ ropivacaine 20 ml locally between the bilateral multifidus and longissimus muscles in group MP.TLIP block was performed by advancing the block needle in a medial to lateral direction and injecting 0.5％ ropivacaine 20 ml locally between the bilateral longissimus and iliocostalis muscles in group LP.The identification rate and distinction score between multifidus and iliocostalis muscles obtained from ultrasonic images were recorded before block in MP and LP groups.All the patients received PCIA until 48 h after surgery.PCIA solution contained sufentanil 100 μg and tropisetron 10 mg diluted to 100 ml with 0.9％ normal saline.The PCA pump was set up with a 2 ml bolus dose,a 15-min lockout interval and background infusion at a rate of 1 ml/h.When visual analogue scale score at rest ＞4 after surgery,parecoxib 40 mg was intravenously injected for rescue analgesia.The development of adverse reactions such as nausea and vomiting was recorded within 48 h after surgery.Results The identification rate and distinction score of the iliocostalis was significantly higher than that of the multifidus (P＜0.05).Compared with group P,the intraoperative consumption of propofol and remifentanil was significantly decreased,the pressing times of PCA,amount of drugs consumed in PCA and consumption of parecoxib were decreased within 48 h after surgery (P＜0.05),and no significant change was found in the incidence of nausea or vomiting in MP and LP groups (P＞0.05).There was no significant difference in the parameters mentioned above between group MP and group LP (P＞0.05).Conclusion Ultrasound-guided medial and lateral approaches to TLIP block is helpful in achieving low-dose opioid anesthesia mode and more helpful in enhancing the efficacy of PCIA when used for lumbar spinal fusion.

Objective To evaluate the role of hippocampal CD200 receptor 1(CD200R1)in peri-operative neurocognitive disorders(PND)in mice.Methods Sixty clean-grade male C57BL/6 mice,aged 9-10 months,weighing 32-38 g,were used in the study.The experiment was performed in two parts.Ex-periment Ⅰ Thirty-six mice were divided into 2 groups(n＝18 each)using a random number table meth-od: control group(group C)and PND group.Group C only received isoflurane anesthesia.Partial left lo-bectomy of the liver was performed under isoflurane anesthesia in group PND.Contextual fear conditioning test was performed at 1,3 and 7 days after surgery,and the freezing time was recorded.The mice were then sacrificed,and the hippocampus was isolated for determination of interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)contents(by enzyme-linked immunosorbent assay)and CD200 and CD200R1 expression(by Western blot).ExperimentⅡ Twenty-four mice were divided into 2 groups(n＝12 each)using a random number table method: CD200-Fc group and IgG1-Fc group.Recombinant proteins CD200-Fc and human IgG1-Fc were injected into the lateral cerebral ventricle in CD200-Fc group and IgG1-Fc group,respectively.Partial left lobectomy of the liver was performed after the end of injection.Contextual fear conditioning test was performed at 1 and 3 days after surgery,and the freezing time was recorded.Re-sults Experiment Ⅰ Compared with group C,the freezing time in the contextual fear conditioning test was significantly shortened,and the contents of IL-1β were increased at 1 and 3 days after surgery,the contents of TNF-α were increased at 3 and 7 days after surgery,and the expression of CD200 and CD200R1 was up-regulated at 1 day after surgery in group PND(P＜0.05).ExperimentⅡ Compared with IgG1-Fc group,the freezing time in the contextual fear conditioning test was significantly prolonged at 1 day after surgery in CD200-Fc group(P＜0.05).Conclusion Up-regulated expression of hippocampal CD200R1 is the endogenous protective mechanism of PND in mice.

Objective: To evaluate the role of hippocampal CD200 receptor 1 (CD200R1) in perioperative neurocognitive disorders (PND) in mice. Methods: Sixty clean-grade male C57BL/6 mice, aged 9-10 months, weighing 32-38 g, were used in the study.The experiment was performed in two parts.Experiment Ⅰ Thirty-six mice were divided into 2 groups (n=18 each) using a random number table method: control group (group C) and PND group.Group C only received isoflurane anesthesia.Partial left lobectomy of the liver was performed under isoflurane anesthesia in group PND.Contextual fear conditioning test was performed at 1, 3 and 7 days after surgery, and the freezing time was recorded.The mice were then sacrificed, and the hippocampus was isolated for determination of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) contents (by enzyme-linked immunosorbent assay) and CD200 and CD200R1 expression (by Western blot). Experiment Ⅱ Twenty-four mice were divided into 2 groups (n=12 each) using a random number table method: CD200-Fc group and IgG1-Fc group.Recombinant proteins CD200-Fc and human IgG1-Fc were injected into the lateral cerebral ventricle in CD200-Fc group and IgG1-Fc group, respectively.Partial left lobectomy of the liver was performed after the end of injection.Contextual fear conditioning test was performed at 1 and 3 days after surgery, and the freezing time was recorded. Results: Experiment Ⅰ Compared with group C, the freezing time in the contextual fear conditioning test was significantly shortened, and the contents of IL-1β were increased at 1 and 3 days after surgery, the contents of TNF-α were increased at 3 and 7 days after surgery, and the expression of CD200 and CD200R1 was up-regulated at 1 day after surgery in group PND (P<0.05). Experiment Ⅱ Compared with IgG1-Fc group, the freezing time in the contextual fear conditioning test was significantly prolonged at 1 day after surgery in CD200-Fc group (P<0.05). Conclusion Up-regulated expression of hippocampal CD200R1 is the endogenous protective mechanism of PND in mice.

Objective To compare the efficacy of ultrasound-guided lumbar epidural access using paramedian transverse scanning (PMTS) versus paramedian saggital scanning (PMSS) with the needle inplane.Methods Fifty American Society of Anesthesiologists physical status Ⅰ-Ⅲ patients,aged 50-75 yr,weighing 55-85 kg,undergoing lower extremity surgery under combined spinal-epidural anesthesia,were divided into PMSS group (n=25) and PMTS group (n=25) using a random number table.The realtime ultrasound-guided lumbar epidural access (L3,4) was performed using PMTS and PMSS in PMTS and PMSS groups,respectively.The visibility of ligamentum flavum,posterior and anterior dura maters,posterior epidural space on the prepuncture ultrasound images,imaging quality score,time for puncture and depth of puncture were recorded.The development of air ultrasonic contrast sign and backflow of cerebrospinal fluid from the spinal needle were recorded.The development of adverse reactions such as paresthesia and hypokinesia was also recorded on 2 days after operation.Results Compared with group PMSS,the time for puncture was significantly shortened,the depth of puncture was shallower (P＜0.05),and no significant change was found in the visibility of spinal structure,imaging quality score or air ultrasonic contrast sign and incidence of backflow of cerebrospinal fluid in group PMTS (P＞0.05).No significant change was found in adverse reactions such as paresthesia or hypokinesia between the two groups (P＞0.05).Conclusion PMTS provides clear imaging and simple and convenient operation in guiding lumbar epidural access with the needle in-plane when compared with PMSS,and it is worthy of clinical application.

Objective To observe the effect of ultrasound-guided single erector spinae plane (ESP ) block combined with patient-controlled intravenous analgesia (PCIA ) on postoperative analgesia in patients undergoing lobectomy performed via video-assisted thoracoscope. Methods Forty patients (20 males and 20 females,ASA physical status Ⅰ or Ⅱ),scheduled for e-lective video-assisted thoracoscopic lobectomy,were randomly assigned into two groups,ESP block combined with PCIA group (group EP)and PCIA only group (group P).ESP block was given to pa-tients in group EP before operation,and its effect was evaluated by testing the area of block.VAS scores were recorded at 1,6,18,24 and 48 h after operation.The frequency for compress PCIA,the volume of analgesic drugs,the consumption of flurbiprofen axetil and the side-effects were recorded as well.Results ESP block was accomplished in group EP with sensory loss from T2-T8 or T3-T7 over the entire posterolateral aspect of the hemithorax.And there were no puncture-related complications. The VAS scores both at rest and coughing in group EP were lower than those in group P (P <0.05). The compress PCA numbers,the volume of analgesic drugs and the consumption of flurbiprofen axetil were significantly less in group EP than those in group P (P <0.05).Only nausea and vomiting were observed as postoperative side effects,and there were no significant differences between the two groups.Conclusion Ultrasound-guided single erector spinae plane block combined with PCIA is a sa-fer and more effective method for the analgesia of thoracic operation than PCIA only.

Objective To evaluate the changes in the expression of neuroligin1 in excitatory postsynaptic membrane of the spinal dorsal horn in a rat model of inc isional pain.Methods Forty-eight pathogen-free healthy adult male Sprague-Dawley rats,aged 6-8 weeks,weighing 280-320 g,were divided into control group (group C,n =12) and incisional pain group (group Ⅰ,n=36) using a random number table.A1 cm long incision was made in the plantar surface of the right hindpaw in group Ⅰ.Cumulative pain score (CPS) was assessed and mechanical paw withdrawal threshold to von Frey stimuli was measured at 3 hand 1 and 3 days after operation (T1,2,3).The animals were then sacrificed and their lumbar segments (L3-6) of the spinal cord were removed for detection of the expression of neuroligin1,postsynaptic density-95 protein (PSD-95),glutamate receptor 1 (GluR1) and GluR2 in the postsynaptic membrane of spinal dorsal horn (by Western blot) and co-expression of neuroligin1 with PSD-95 in spinal dorsal horn (by co-immuno-precipitation).Results Compared with group C,CPS was significantly increased and mechanical paw withdrawal threshold was decreased at T1-3,and the expression of neuroligin1 and GluR1 in the postsynaptic membrane of spinal dorsal horn at T1,2 and co-expression of neuroligin1 with PSD-95 at T1 were up-regulated in group Ⅰ (P＜0.01 or 0.05).Conclusion The development and maintenance of incisional pain is related to the signaling pathway regulated by neuroligin1 in excitatory postsynaptic membrane of the spinal dorsal horn of rats.

Objective To evaluate the clinical efficacy of “Shamrock” ultrasound images?guided lumbar sympathetic ganglion blockade ( LSGB) . Methods Sixty patients of both sexes, aged 18-60 yr, weighing 50-70 kg, of American Society of Anesthesiologists physical statusⅠorⅡ, undergoing unilater?al LSGB, were divided into groupⅠ ( n=30) and group Ⅱ ( n=30) using a random number table. In group Ⅰ, unilateral LSGB was performed at the L2 level under ultrasound guidance with paramedian trans?verse scanning. In groupⅡ, unilateral LSGB was performed at the L2 level under ultrasound guidance with“Shamrock” ultrasound images. After final needle position was confirmed, 2% lidocaine 6?0 ml was ad?ministered in each patient. At 20 min before and after LSGB, the visual analogue scale scores and skin temperature of the big toe of the affected foot were recorded, and the successful blockade and visibility of important paravertebral structures on ultrasound images were recorded during puncture. Results The visu?al analogue scale scores were significantly lower, and the skin temperature on the affected side was signifi?cantly higher after LSGB than before LSGB in both groups ( P<0?05) . The important paravertebral struc?tures such as erector spinae, quadratus lumborum, psoas major, transverse process of L2 vertebrae, and the curved edge of L2 vertebrae were visible in both groups. The visibility rate of the inferior vena cava or ab?dominal aorta on ultrasound images and the success rate of blockade were significantly lower in group Ⅰthan in group Ⅱ (P<0?01). Conclusion Compared with paramedian transverse scanning, LSGB has some advantages such as real?time monitoring, higher success rate of blockade, better efficacy and avoiding damage to great vessels when performed under “Shamrock” ultrasound image guidance.

Objective To explore the differences of Th17 population and serum transforming growth factor (TGF)-β1 levels between early-and late-stage primary biliary cirrhosis (PBC) and their roles in pathogenesis.Methods Peripheral Th17 counts were analyzed by flow cytometry.The expression of IL-17A in peripheral blood mononuclear cells and TGF-β1 were measured by real-time quantitative polymerase chain reaction.Serum concentration of TGF-β1 was measured by enzyme-linked immunosorbent assay.Liver biopsies were stained with hematoxylin-eosin to determine the pathological stage.Results were evaluated using KrustalWallis test followed by Mann-Whitney U tests for comparisons of Th17 population between patients with early and late PBC,patients with chronic hepatitis B (CHB) and health controls (HCs).ANOVA followed by LSD t-tests were used for comparing IL-17 mRNA,TGF-β1 mRNA and TGF-β1 serum concentration between groups.The correlations between Mayo risk score and peripheral Th17 of PBC patients,Mayo risk score and serum concentration of TGF-β1 was analyzed by Pearson correlation analysis separately.Results The peripheral Th17 population increased in patients with early PBC (1.03±0.33)％,compared to those with late PBC [(0.48± 0.13％,U=14.0,P＜0.01],CHB [(0.56±0.35)％,U=104.5,P＜0.01],and HCs [(0.36±0.17)％,U=8.0,P＜0.01],while TGF-β1 changed in the opposite direction.Serum concentration of TGF-β1 elevated in late PBC (43.0± 18.7) ng/ml compared with early PBC (29.5±12.2) ng/ml,t=2.85,P=0.006.Conclusion The opposite changes of Th17 population and TGF-β1 level in early and late PBC indicated their different roles in different stages.Th17 may contribute to the autoimmune response in early PBC,participate in the occurrence of autoimmune inflammation,while TGF-β1 to fibrogenesis in late stage.In addition,the possible regulation mechanisms of differentiation of Th17 by TGF-β1 cannot be ignored.

Objective To describe the immunological characteristics of refractory primary biliary cirrhosis compared with the typical patients for more than 1 year's administration of UDCA.Methods Sixty patients treated with UDCA for more than 1 year in our clinic were enrolled into this study.According to the response to UDCA by Paris criteria,patients were divided into refractory group (23 patients) and typical groups (37 patients).The recent peripheral lymphocyte subsets and cytokines of the two groups were tested and analyzed.One-way ANOVA and t test were used for statistical analysis.Results ① One-year treatment after diagnosis,there were no differences between the two groups in the distribution of peripheral lymphocytic subsets,meanwhile,the two groups had higher percentage of B cells,CD4+T cells,CD4+CD28+T cells and CD8+ CD28-T cells than healthy controls respectively.② The serum levels of IL-6 [(0.8±0.9) pg/ml vs (0.3±0.4) pg/ml] and HGF were higher in the refractory group than other groups.Conclusion During the plateau phase,refractory PBC patients have higher serum levels of IL-6 and HGF,which probably suggest that the refractory PBC patients may have severe immunologic disturbance in vivo.