Objective To investigate the effect of intrathecal injection (IT) of dexmedetomidine targeting Toll-like receptor 3 (TLR3) on neuropathic pain and spinal cord levels of TLR3 mRNA,interleukin-1β(IL-1β),tumor necrosis factor-alpha (TNF-α) proteins in rat model of chronic constriction injury (CCI).Methods Male Sprague-Dawley rats were randomly divided into five groups(n =10):the sham group(intrathecal normal saline,IT NS),CCI group (CCI + IT NS),DEX-pre group (CCI + IT DEX pre 2ds),DEX-post group (CCl + IT DEX post 7ds) and DEX + ATIP group (CCI + IT DEX + ATIP).The lumbar intrathecal catheters were implanted in L5_6 of rats and CCI models were established as previously described.The thermal and mechanical nociceptive thresholds were assessed by paw withdrawal latency(PWL) to radiant heat and yon Frey filaments.The DEX was administered intrathecally for 7 days starting from 2 day before surgery or 7day after surgery.The spinal cord expression of TLR3 mRNA was assessed by real-time polymerase chain reaction (PCR).Levels of IL-1β,TNF-α in spinal cord were detected by enzyme-linked immunosorbent assay (ELISA).Results Compared with the sham group,animals in CCI group had significandy lower mechanical (F =12.73,P ＜ 0.05) and thermal pain thresholds (F =14.65,P ＜ 0.05),higher expression of TLR3 mRNA (F =11.03,P ＜ 0.05) and levels of IL-1 β (F =9.67,P ＜ 0.05),TNF-α(F =8.78,P ＜ 0.05) in the spinal cord (P ＜ 0.05).Rats in DEX-pre group had significantly higher mechanical (F =11.03,P ＜ 0.05) and thermal pain thresholds (F =15.03,P ＜ 0.05) and significantly lower expression of TLR3 mRNA (F =14.65,P ＜0.05) and levels of IL-1β (F =12.51,P＜0.05,TNF-α (F =9.01,P ＜0.05) in the spinal cord compared with those in the CCI group (at any observed time points after ligation,but most significantly at 7 d).And the effects of DEX-pre group were abated by IT ATIP at the same time or 7days after surgery alone (P ＜ 0.05).Conclusions Intrathecal injection of DEX can decrease the levels of inflammatory factors by decreasing the TLR3 mRNA in the spinal cord of rats and prophylactic relieve the neuropathic pain induced by CCI.

Objective To investigate the effect of remote ischemic preconditioning (RIPC) combined with dexmedetomidine on the lung injury during one-lung ventilation (OLV) in the patients undergoing thoracic surgery. Methods Eighty ASA physical status I or Ⅱ patients, scheduled for elective radical operation for esophageal cancer, were randomly divided into 2 groups(40 patients each group) using a random number table: control group and RIPC combined with dexmedetomidine group (ORD group). In ORD group,10 min after endotraeheal intubation, RIPC was induced by 3 cycles of 5 min lower extremity ischemia followed by 5 min reperfusion, and at the same time a loading dose of dexmedetomidine 1.0 μg/kg was infused intravenously over 15 min and then dexmedetomidine was infused at a rate of 0.5 μg/(kg·h) until the end of operation. At 0, 30 min, 1 h and 2 h of OLV(T1-4), blood samples were obtained from the radial artery for blood gas analysis and determination of plasma concentrations of tumor necrosis factor-α (TNF-α), interleukin (IL)-1βand IL-10.Oxygenation index and respiratory index were calculated. Exhaled breath condensate was collected at T1, T3 and T4, and the pH value was measured. Results The respiratory index at T2-4 in 2 groups were significantly higher than those at T1, control group: 1.16 ±0.12, 1.02 ±0.10 and 0.97±0.12 vs. 0.49±0.06, ORD group: 0.84±0.15, 0.72±0.12 and 0.65±0.10 vs. 0.48±0.08, there were statistical differences (P<0.05). The oxygenation index at T2-4 in 2 groups were significantly lower than those at T1, control group: (287.1±21.8), (306.8±35.2) and (312.9±25.5) mmHg (1 mmHg=0.133 kPa) vs. (426.5±39.0) mmHg, ORD group: (335.0±34.7), (341.1±41.3) and (359.1±38.8) mmHg vs. (433.6±23.8) mmHg, there were statistical differences (P<0.05). Compared with control group, the respiratory index at T2-4 in ORD group were elevated, the oxygenation index at T2-4 in ORD group were depressed, there were statistical differences (P<0.05). The TNF-α and IL-1β at T3-4 in 2 groups were significantly higher than those at T1, control group: (31.4±6.7) and (38.3±7.2) μg/L vs. (16.2±5.1) μg/L, (7.2±1.6) and (12.3±4.2) μg/L vs. (3.0±0.7) μg/L, ORD group: (21.7±5.4) and (23.4±5.1) μg/L vs. (16.3±4.7) μg/L, (4.8±0.9) and (6.3±1.6) μg/L vs. (2.9±0.8) μg/L, there were statistical differences (P<0.05). The pH value of exhaled breath condensate at T3-4 in 2 groups were significantly lower than those at T1, control group: 6.41±0.23 and 6.33±0.21 vs. 6.93±0.35, ORD group: 6.79±0.30 and 6.74±0.33 vs. 7.07±0.22, there were statistical differences (P<0.05). The IL-10 at T4 in 2 groups were significantly higher than those at T1, control group:(30.6±6.3) μg/L vs. (19.2±5.3) μg/L, ORD group: (41.3±5.2) μg/L vs. (19.5±4.9) μg/L, there were statistical differences (P<0.05). Compared with control group, the TNF-α and IL-1β at T3-4 in ORD group were depressed, the pH value of exhaled breath condensate at T3-4 in ORD group were elevated, the IL-10 at T4 in ORD group was elevated, there were statistical differences (P<0.05). Conclusions RIPC combined with dexmedetomidine can inhibit inflammatory responses and reduce airway acidification, thus attenuate the lung injury during OLV in the patients undergoing thoracic surgery.

Objective:To detect the methylation status of insulin-like growth factor Ⅱ(IGF-Ⅱ)gene promoter P3 in salivary pleo-morphic adenoma(SPA).Methods:The methylation of IGF-Ⅱ gene promtor P3 was examined in 26 cases of salivary pleomorphic adenoma with adjacent normal salivary gland tissues,1 0 cases of salivary gland malignant tumor (except malignant pleomorphic ade-noma)and 1 0 cases of normal salivary gland tissue by nested methylation specific polymerase chainreaction(nMSP),1 0 samples(3 SPA and controls,2 malignance and controls)were examined by pyrosequencing.Results:9 out off the 26 SPA showed lower level methylation oevel of IGF-II gene promoter P3.Normal salivary gland and salivary gland malignant tumor tissue did not.Conclusion:IGF-II gene promoter P3 with low level of methylation may play a role in the development of SPA.

Objective To investigate the correlation and risk factors between vaginal intraepithelial neoplasia (VAIN) and cervical intraepithelial neoplasia (CIN).Methods A total of 121 cases of VAIN patients was retrospectively analyzed with examination results such as clinical manifestations,liquid based cytology (TCT),human papilloma virus infection,virus infection type,and clinical data of treatment and follow up.Results VAIN Ⅰ,VAIN],and VAIN Ⅲ] were accounted for 33.9％ (41/121),38.0％ (46/121),and 24.4％ (34/121) ; for 40 or less years old patients,VAIN Ⅲ was accounted for 10.7％ (3/28) ; for more than 40 years old patients,VAIN Ⅲ was accounted for 33.3％ (31 /93).Among 121 VAIN patients,77.7％ (94/121) patients had CIN history,15.7％ of which (19/121) had a history of cervical cancer; 27.3％ (33/121) with hysterectomy history,of which 75.8％ (25/33) was due to cervical intraepithelial neoplasia and cervical cancer resection of the uterus.Papilloma viral load in patients with VAIN Ⅰ was detected with a (HPV-HC2) positive rate of 87.8％ (36/41),while in VAIN Ⅱ and VAIN [patients,the positive rate was 100％,the infection of high risk type of HPV ratio was 95.9％ (116/ 121).of which the mixed infection was accounted for 56.9％ (66/116).There was 94.6％ in oatients with VAIN (114/121),and liquid-based cytology test results suggest abnormality; 88.4％ (107/121) in patients with VAIN lesions occurred in upper 1/3 of vaginal.After diagnosed cervical disease,the onset time of VAIN was (3.45 ± 2.02) years,non-total-hysterectomy was (3.24 ± 1.97) years,after hysterectomy to pathological diagnosis time for VAIN was (5.01 ± 3.95) years:for the diagnosis of VAIN disease after resection of cervical original time was (3.96 ± 2.99) years,and rather than non cervical disease resection was an average of (9.94 ±5.37) years.In the course of treatment of the 12l cases of CIN patients,6 cases of patients were progressed to invasive carcinoma.Conclusions The clinical manifestation of VAIN is similar to CIN,the principle of diagnosis and treatment of CIN can also apply to VAIN,high risk HPV infection virus,cervical intraepithelial neoplasia are the risk factors for VAIN.

Animals ; Dose-Response Relationship, Drug ; Female ; Humans ; Metals, Heavy ; analysis ; pharmacology ; Placenta ; chemistry ; drug effects ; physiology ; Pregnancy ; Rats

Objective:To investigate the activated state of TH1/TH2 cytokines and T lymphocytes and to explore the pathogenesis of ankylosing sondylitis.Methods:Cytokine levels of Th1(IFN-?、TNF-?、IL-2)and Th2(IL-10、IL-5、IL-4) in plasma, percentages of CD3 +、CD4 +、CD8 + T cells、B cells(CD19 +) NK cells(CD16 +56 +)and CD3 +HLA-DR +、CD4 +HLA-DR +、CD8 +HLA-DR + T cells in peripheral blood lymphocytes were detected by Flow Cytometry.Results:In patients with AS ,plasma levels of TNF-?、IL-2 were significantly lower than that of healthy controls. IL-10 were significantly higher than that of healthy controls. In AS patients, percentages of CD3 +and CD8 + T cell from peripheral blood lymphocytes were significantly lower than that of healthy controls. Percentages of CD8 +HLA-DR + T cell were significantly lower than that of healthy controls. CD4 +HLA-DR +T cell was significantly highter than that of healthy controls.Conclusion:In patients with AS , lower levels of TNF-?、 IL-2 and higher level IL-10 at plasma indicate an inclination between TH1 and TH2, such as an impaired TH1 cytokine profile and an activated TH2 cytokine profile, especially in TNF-?.

Heart Defects, Congenital ; diagnostic imaging ; Humans ; Organ Size ; Radiography, Thoracic ; Syndrome

Adult ; Cytokines ; metabolism ; Female ; Gene Expression ; Humans ; Interleukin-2 ; blood ; Interleukin-4 ; blood ; Male ; Semaphorins ; genetics ; metabolism ; T-Lymphocytes, Helper-Inducer ; metabolism ; Thrombocytopenia ; genetics ; metabolism

Objective To investigate the effects of intrathecal injection (IT) of agonist and antagonist of N-methyl-D-aspartate receptor subunit 1 (NMDA NR1) on pain threshold and spinal levels of glutamate and glutamate transporter-1 (GLT-1) in rat model of chronic constriction injury (CCI) induced neuropathic pain.Methods Sprague-Dawley (SD) rats were randomly divided into 4 groups (Sham,CCI,NM-DA,and Humanin).The CCI model was established by right sciatic nerve constriction.The thermal and mechanical thresholds were assessed by paw withdrawal latency (PWL) to radiant heat and yon Frey filaments at 1,3,5,7,10 and 14 days as well as behavior after CCI.The NMDA and Humanin groups were administered intrathecally for 3 days before surgery.Spinal expression of GLT-1 assessed by Weston blotting and levels of glutamate were measured by enzyme-linked immunosorbent assay (ELISA).Results Compared to Sham group,the rats in CCI group gradually appeared the symptoms of toe close together,foot valgus and repeated licking to the operative side of the hind legs after surgery,and the paw withdrawal threshold (PWT),and PWL were greatly decreased,reaching the lowest level on the 7th day.Meanwhile,the glutamate content was increased,and the GLT-1 expression was decreased in spinal cord (P ＜ 0.05).Compared to CCI group,the rats in NMDA group were observed with further decrease in PWT,PWL and GLT-1 expressions at all observed timepoints (P ＜ 0.05),but increase in glutamate content in spine cord (P ＜0.05).Compared to CCI group,the rats in Humanin group were observed with increase in PWT,PWL and GLT-1 expressions at all observed timepoint (P ＜ 0.05),but decrease in glutamate content in spine cord (P ＜ 0.05).Conclusions NMDA receptor NR1 subunit participated in regulating neuropathic pain,inhibiting NMDA receptor NR1 subunit can alleviate neuropathic pain by down-regulating of glutamate and GLT-1.

Objective To investigate the beneficial effects and possible mechanisms of intrathecal injection of dexmedetomidine (DEX) in protection of spinal cord ischemia-reperfusion injury.Methods Spinal cord ischemia-reperfusion injury was induced in rabbits by infrarenal aortic occlusion for 30 minutes.Twenty-four rabbits were randomly divided into four groups:sham group,I/R group,DEX group (1 μg/kg dexmedetomidine by intrathecal injection),DEX + ATIP group (1 μg/kg dexmedetomidine and 0.5 μg/kg atipamezole (ATIP) by intrathecal injection).Physiological indices were assessed and motor neurons in the ventral gray matter were counted by histological examination.The expression of total extracellular signal-related kinase (t-ERK),phospho-extracellular signal-related kinase (p-ERK),and caspase 3 were assessed by Western blotting and real-time polymerase chain reaction (RT-PCR).The water content in spines was also measured.Results Intrathecal injection of dexmedetomidine minimized the neuromotor dysfunction and histopathological deficits(F =14.32,P ＜ 0.05) and attenuated the influences of peroxidation at 24 hours after spinal cord ischemia-reperfusion injury.The physical indices during experiment were comparable among all groups.In addition,intrathecal injection of dexmedetomidine reduced the excessive expression of caspase 3 mediated by ERK signal pathway(F =15.45,P ＜ 0.05).Conclusions Pre-emptive intrathecal injection of dexmedetomidine produced beneficial effects on spinal cord after spinal cord ischemia-reperfusion injury in a rabbit model of transient aortic occlusion.This beneficial effect was partly attributed to the inhibition of caspase 3 mediated by ERK signal pathway,which represents a potential therapeutic approach to mitigate spinal cord injury after aortic occlusion.