BACKGROUND:Dexmedetomidine is an efficient, highly selective alpha-2 adrenergic receptor agonist, with sedative, analgesia and anti-anxiety effects, it has little impact on the respiration.
OBJECTIVE:To observe the analgesic effect induced by intrathecal injection of dexmedetomidine in rat model of spared nerve injury.
METHODS:A total of 60 male Sprague-Dawley rats were randomly divided into three groups (n=12):normal control group, dexmedetomidine group and saline group. Except for the normal control group, spared nerve injury model was established in the rats of dexmedetomidine group and saline group. Dexmedetomidine group was treated with intrathecal injection of dexmedetomidine 3μg/kg every day within 14 days after injury. Saline group was given equal volume of saline for 14 days. The thermal withdrawal latency and mechanical withdrawal threshold were measured respectively before injury, after injury, before injection, and 2, 7, 14 days after intrathecal injection. Four rats were sacrificed in each group at day 2, 7 and 14 after injection, and the lumbar segments (L 4-6 Hematoxylin-eosin staining was performed to detect the morphology of the spinal dorsal horn neurons and ) of the spinal cord were removed. Real-time RT-PCR and western blot analysis were used to determine the expression of protein kinase C mRNA and protein in the spinal dorsal horn neurons. immunohistochemistry staining was carried out to assess the expression level and distribution of protein kinase C.
RESULTS AND CONCLUSION:The thermal withdrawal latency and mechanical withdrawal threshold in dexmedetomidine group and saline group were significantly decreased compared with normal control group before or after injection (P<0.05). However, both the thermal withdrawal latency and mechanical withdrawal threshold in dexmedetomidine group after intrathecal injection were significantly higher than those in saline group (P<0.05). The protein kinase C expression in spinal dorsal horn neurons was significantly decreased in dexmedetomidine group compared with saline, and reached to the most lowest levels as normal control group on 14 days after injection. Moreover, the apoptosis of spinal dorsal horn neurons in dexmedetomidine group was lighter than that in saline group, and was similar to the morphology of neurons in normal control group on 14 days after injection. Intrathecal injection of dexmedetomidine could attenuate the hyperalgesia induced by spared nerve injury, which might be associated with the inhibition of protein kinase C expression in spinal dorsal horn.

BACKGROUND:Dexmedetomidine is an effective high-selectivityα2-adrenoceptor agonist that has sedative, analgesic, anxiolytic effects, but slightly affects respiration.
OBJECTIVE:To observe the analgesic effect of dexmedetomidine on selective damage of sciatic nerve branch in a rat model by intrathecal injection.
METHODS:A total of 36 male Sprague-Dawley rats were randomly divided into normal control group, physiological saline group and dexmedetomidine group. A rat model of selective damage of sciatic nerve branch was established by knotting off the common peroneal nerve and tibial nerve in the physiological saline group and dexmedetomidine group. Rats in the dexmedetomidine group were daily injected with dexmedetomidine 3μg/kg by intrathecal injection within 14 days after injury. Rats in the physiological saline group were injected with physiological saline.
RESULTS AND CONCLUSION:Compared with the physiological saline group, the mechanical withdrawal threshold and the thermal withdrawal latency were significantly increased in the dexmedetomidine group (P<0.05). Neuronal nitric oxide synthase mRNA and protein expression levels were significantly decreased in the spinal dorsal horn (P<0.05). The injury to spinal dorsal horn neurons was obviously lessened. Moreover, neuronal nitric oxide synthase mRNA and protein expression levels and the injury to spinal dorsal horn neurons were similar between 14 days after administration and normal control group. Results indicated that intrathecal injection of dexmedetomidine could inhibit the expression of neuronal nitric oxide synthase in the spinal dorsal horn and relieve the pain induced by sciatic nerve injury.

Objective:To investigate the effect of the combined general and epidural anesthesia on tissue perfusion and intestinal barrier in elderly patients undergoing radical resection of colorectal cancer.Methods:A total of 118 elderly patients with colorectal cancer admitted to our hospital from January 2018 to September 2019 were randomly divided into two groups: a single general anesthesia(control, n=59)and combined general and epidural anesthesia(observation, n=59). Two groups underwent radical resection of colorectal cancer.The perioperative parameters were compared between the two groups, including tissue perfusion[central venous-to-arterial carbon dioxide difference(Pcv-aCO 2), oxygen delivery index(DO 2I), oxygen consumption index(VO 2I), difference between central venous and arterial lactate(Dcv-aLac), oxygen extraction rate(O 2ER), central venous oxygen saturation(ScvO 2)], and intestinal barrier[diamine oxidase(DAO), D-lactic acid(D-Lac)]. Results:Compared with the control group, the ScvO 2 during T2-T4 periods was increased in the observation group, and the VO 2I, Dcv-aLac and Pcv-aCO 2 during T1-T4 periods were reduced in observation group( P<0.05). The DO 2I during T1-T4 periods was slightly higher in the observation group than in the control group, and the O 2ER was slightly lower in the observation group than in the control group, but the differences were not statistically significant, ( P>0.05). In the both two groups, the D-Lac and DAO levels showed a gradual upward trend during T1-T5 periods and a gradual downward trend during T5-T6 periods.The D-Lac and DAO levels during T2-T6 periods were lower in observation group than in the control group( P<0.05)[during abdominal exploration(T1); invitrolesion(T2); before abdominal closure(T3); after surgery(T4); postoperative day 1(T5); postoperative day 3(T6)]. Conclusions:General anesthesia combined with epidural anesthesia in elderly colorectal cancer patients undergoing radical resection can stabilize perioperative tissue perfusion, decrease intestinal barrier injury and increase anesthetic effect.

Objective To detect eight kinds of clinical common pathogenic bacteria by DNA microarray.Methods Eight kinds of common pathogenic bacteria,including Staphylococcus aureus,Pseudomonas aeruginosa,Klebsiella pneumoniae,Escherichia coli,Proteus mirabilis,Enterobacter aerogenes,Pseudomonas fluorescens,Shigella sonnei were collected.Universal primers were designed to amplify 16S rRNA gene fragment from the genomic DNA of the eight bacteria,and probes were designed in the highly variable regions.DNA microarray detection system was established and used for detection of colleted bacteria.A total of 50 samples were collected from the Zhongnan Hospital of Wuhan University,including 6 blood samples,32 sputum samples,9 feces samples and 3 bronchoscope lavage samples.DNA were extracted and detected by the established DNA microarray system.Results The desired fragments were well amplified by the self-designed universal primers.The selected probes had good detection results according to repeated detection.Of the 50 samples detected,pathgenic bacteria were accurately detected in 47 samples.Other three samples were not detected as those bacteria were not included in the chip.By optimizing the detection process,the results could be reported within 8 hours.Observation of probe signal attenuation indicated that even attenuated after 60 days,but the attenuation did not affect the results.Conclusion A microarray system was established for detection of clinical common bacteria accurately and quickly,which provided foundation for its clinical application.

Objectiye To investigate the effect of selective COX-2 inhibitor, nimesulide, on inhibiting proliferation of the human acute myeloid leukemia HL-60 cells. Methods HL-60 cells were treated with different concentration of nimesulide. HL-60 cell proliferation was examined by CCK-8 method. Flow cytometry, Western blotting and ELISA were used to measure the effect of nimesulide on apoptosis, cell cycle,COX-2, PGE2, bax, bcl-2 and c-myc. Results Nimesulide inhibited HL-60 cells proliferation in a dose and time dependence manner. Nimesulide induced cell apoptosis and arrested cell cycle in G0-G1 phase. The expression of COX-2 protein declined after treated with nimesulide 48 h, the total apoptosis in 100, 200,400 μmol/L nimesulide-treated group and control group were (24.97 ± 6.36) %, (34.22 ± 5.76) %, (44.59 ±6.69) % and (4.11 ± 1.26) %, there were significant differences (P ＜ 0.05). Nimesulide inhibited the synthesis of PGE2, the expressions of bcl-2 and c-myc protein and upregulated the expression of bax protein simultaneity.Conclusion Nimesulide significantly inhibited the proliferation of HL-60 cells and induced cell apoptosis,which may be associated with the downregulation of COX-2 expression, reduction of PGE2 synthesis, arrest of cell cycle and regulation bcl-2, c-myc and bax protein expression.

Objective To detect the expression of VEGF in NHL and analyze the relation of the expression levels with malignant aggressiveness,treatment response,and prognosis.Methods The expression of VEGF in lymph nodes taken from 39 NHL patients Wag measured by immunohistochemical-staining method.9 patients with benign lymphadenopathy were acted as control.Results The expression of VEGF in NHL(79.5%)was higher than that in the contrel(44.4%)(P=0.048＜0.05).In NHL,the VEGF level was higher in aggressive lympboma than that in indolent lymphoma(x2=5.284,P=0.044＜0.05).The patients had the higher-level expression as the Ann Arbor stage Wag higher,and the patients who had the higher-level expression of VEGF had higher serum LDH level,lower chemotherapy remission,unfavorable prognosis and lower 3-year survival (P＜0.05).Conclusion The expression of VEGF in NHL was increased.It was correlated with histopathological grade,Ann Arbor stage,chemotherapy response and prognosis.

Objective To investigate the effect of membrane-bound prostaglandin E2 synthase 1 (mPGES-1) inhibitor MK886 on cell cycle of the human acute myeloid leukemia HL-60/A cells.Methods Flow cytometry,Western blot and ELISA were used to measure the difference of cell cycle,expression of cyclin D1, mPGES-1 among HL-60/A cells,MNC and HL-60 cells.The effect of MK886 on cell cycle,cyclin D1,mPGES-1,PGE2,P-Akt and c-myc of HL-60/A cells were observed.Results Compared with MNC and HL-60 cells,the expression of cyclin D1 and mPGES-1 were higher in HL-60/A cells,the percentage of G0-G1 phase was decreased [MNC (62.63±6.58) ％,HL-60 (38.86±2.25) ％,HL-60/A (30.53±2.15) ％]and S phase increased[MNC (12.18±4.43) ％,HL-60 (47.70±1.88）％,HL-60/A (57.56±1.54) ％](all P＜ 0.05).After treated with MK886,cell cycle was arrested in G0-G1 phase.The expression of mPGES-1,cyclin D1,P-Akt and c-myc and synthesis of PGE2 were decreased.Conclusion MK886 can arrest HL-60/A cell cycles in G0-G1 phase,which possibly through down-regulation of mPGES-1/PGE2,reduction cyclin D1,P-Akt and c-myc expression.

Objective Our preliminary study demonstrates that quercetin can inhibit the proliferation of HL-60 cells. This sudy aimed to find some drugs which could have synergistic effects with quercetin on apoptosis of HL-60 cells. Methods HL-60 cells were cultured with bortezomib at different concentrations (1, 2, 4, 8, 16, and 32μmol/L) alone or combined with quercetin at different concentrations for 48 h. HL-60 cells were cultured with lenalidomide at different concentrations (5, 10, 20, 40, 80, 160, and 320 μmol/L) alone or in combination with quercetin at different concentrations for 48 h. The CCK-8 assay was used to determine the effects on proliferation of HL-60 cells. Results Bortezomib significantly inhibited the proliferation of HL-60 cells (P<0.01). IC50 of quercetin was 49.24μmol/L after cells treated by quercetin combined with bortezomib, which was 13.44μmol/L lower than that treated by quercetin alone. Isobolographic analysis revealed the two drugs had synergistic effect. The results of cell viability of HL-60 cells treated by lenalidomide at lower concentrations (5, 10, 20, 40, and 80μmol/L)were not different from those of the control group (P > 0.05). The results of cell viability of HL-60 cells treated by lenalidomide at higher concentrations (160 and 320μmol/L) were lower than those of the control group (P<0.05). IC50 of quercetin after cells treated by quercetin combined with bortezomib was not different from that treated by quercetin alone. Isobolographic analysis revealed the two drugs had no synergistic effect. Conclusions Bortezomib can inhibit the proliferation of HL-60 cells and it has a synergistic effect with quercetin on HL-60 cells. Lenalidomide has a weaker role in inhibition of the proliferation of HL-60 cells, and it has no synergistic effect with quercetin on HL-60 cells.

Objective To explore the correlation of atheroselerosis progression and the expression of platelet derived endothelial nitric oxide synthase (eNOS) in rabbits. Methods A total of 24 male New Zealand white rabbits were used in this study. Six of the animals were fed with normal food (control group). Eighteen rabbits were fed with cholesterol-rich food (1 g/d) for 12 weeks to establish the atherosclerosis model. Among 18 models, 6 rabbits were executed immediately and their aorta and platelet samples were collected for further analysis (model group), 6 rabbits were orally administered with pravastatin (10 rag/d) for additional 12 weeks (treated group), and the remaining 6 rabbits were left untreated until the end of the study (untreated group). The control, treated and untreated animals were then killed, and the aorta and platelet samples were collected for eNOS expression analysis (RT-PCR). Results The aorta samples in model and untreated group exhibited rough intima and a lot of longitudinal fatty streaks, which indicated that atherosclerosis models were established successfully. While in treated group, the degree of atherosclerosis was decreased. The average percent of thickness of fatty streaks or atheroselerotic plaques relative to the whole thickness of vessel walls was 0. 04±0. 02, 0. 82±0. 16, 0. 33±0. 18,0. 77±0. 14 in control, model, treated and untreated group, respectively. The thickness of fatty streaks or atherosclerotic plaques was significantly increased in the model and untreated groups and decreased in treated group compared with the control group (both P<0. 05). The expressions of platelet derived eNOS/mRNA were 1. 02± 0. 28, 0. 41± 0. 27, 1.00 ± 0. 77, 0. 40±0. 29 in control, model, treated and untreated group, respectively. The expression of eNOS/mRNA was markedly decreased in model group and untreated group compared with the control group, but was increased in treated group compared with untreated and model groups (F=3. 544, P = 0. 024). Conclusions There is a negative correlation between eNOS expression and atherosclerosis development, which suggests that the reversal effect of pravastatin on atheroselerosis progression and plaque formation may relate to the expression of platelet derived eNOS.

Objective:To explore the effect of dexmedetomidine on cough reactions and related indexes during recovery from general anesthesia in thyroid tumor surgery.Methods:A total of 90 patients with thyroid tumor who underwent general anesthesia for thyroid tumor surgery from July 2019 to July 2021 in the First People's Hospital of Shangqiu City, Henan Province were selected and divided into the observation group (45 cases) and the control group (45 cases) according to the random number table method. The observation group was given dexmedetomidine 0.5 μg/kg intravenously at the beginning of the surgery, and the intravenous drip time should not be less than 10 min; the control group was given the same dose of normal saline intravenously. The recovery time and extubation time of the two groups were compared, and the incidence of cough reactions during the recovery from general anesthesia was compared. Changes of visual analogue scale (VAS) of pain at 6 h, 24 h and 48 h after surgery, and the changes of stress response indexes [cortisol (Cor), epinephrine (E) and norepinephrine (NE)] and pain factors [prostaglandin E2 (PGE2), neuropeptide Y (NPY) and β-endorphin (β-EP)] before and 48 h after surgery were compared.Results:The recovery time and extubation time in the observation group [(15.62 ± 3.64), (18.27 ± 4.25) min] were faster than those in the control group [(23.12 ± 4.53), (25.65 ± 3.89) min, P < 0.001]. The incidence of cough reactions during recovery from general anesthesia in the observation group [8.89% (4/45)] was lower than that in the control group [28.89% (13/45), P = 0.015]. The VAS score in the observation group was lower than that in the control group at 6 h, 24 h and 48 h after surgery ( P < 0.001). The levels of serum Cor, E and NE at 48 h after surgery in both groups were higher than those before surgery ( P < 0.001); and the serum Cor, E, and NE levels in the observation group were lower than those in the control group at 48 h after surgery ( P < 0.001). The serum PGE2 and NPY levels of the two groups at 48 h after surgery were higher than those before surgery, while β-EP level was lower than that before surgery ( P < 0.001); the serum PGE2 and NPY levels in the observation group were lower than those in the control group at 48 h after surgery, while β-EP level was higher than that in the control group ( P < 0.001). Conclusion:Dexmedetomidine can reduce the cough reactions during recovery from general anesthesia in thyroid tumor surgery, significantly reduce pain, and has little effect on stress response and pain factors.