AIM: To explore the effect of melatonin (MLT) on the apoptosis of thymocytes and splenocytes in mice induced by ionizing radiation and its mechanism. METHODS: The percentages of apoptotic bodies and the DNA lytic rates of thymocytes and splenocytes in mice in vitro and in vivo were detected with flow cytometry and fluorospectrophotometry, respectively. RESULTS: The apoptosis of mouse thymocytes and splenocytes in vitro increased with significant dose-dependence in 0 5-6 0 Gy X-irradiation. When MLT of 2 mmol?L -1 was added into thymocytes or splenocytes in vitro before irradiation with 0 5-6 0 Gy X-rays, the percentages of apoptotic bodies and the DNA lytic rates all decreased significantly as compared with those in the irradiation group. The percentages of apoptotic bodies in these two kinds of cells were 86 25% and 89 22% of those in the irradiation group, respectively, and the DNA lytic rates were 87 23% and 89 16%, respectively. When MLT was injected into intraperitonium in mice 60 min before whole-body irradiation with 2 Gy X-rays, the percentages of apoptotic bodies and the DNA lytic rates were significantly lower than those in the irradiation group, and near or lower than those in the sham-irradiation group. MLT of 0 1-2 5 mg/kg decreased the lymphocyte apoptosis, but without significant dose-dependence. CONCLUSION: The protective effects of MLT on mouse lymphocytes damaged by irradiation in vivo are obvious than those in vitro. [

OBJECTIVETo evaluate the clinical effects of iliolumbar fixation for the sacrum fractures of Denis type II.

METHODSThe clinical data of 86 patients with sacrum fracture of Denis type II treated by iliolumbar fixation from January 2008 to January 2012 were retrospectively analyzed. There were 55 males and 31 females, aged from 17 to 55 years old with an average of 39.1 years. Among them, 73 cases complicated with pelvis fracture and 13 cases with acetabular fracture; 37 cases with sacral neurological symptoms and 49 cases without sacral neurological symptoms. Fracture healing time, nerve function, clinical function and complications were observed in the patients.

RESULTSIn 86 cases, 6 cases were out of followed-up and 80 cases were followed up from 24 to 71 months with an average of 36 months. The mean fracture healing time was 13 weeks (ranged, 10 to 38 weeks). According to Gibbons scoring to evaluate the neurological function, preoperative nerve rehabilitation, lower limbs feeling, lower limbs activity,bladder and rectum function,total score respectively were 0.62 +/- 0.04, 1.54 +/- 0.35, 1.12 +/- 0.18, 0.23 +/- 0.01, 3.46 +/- 0.47 and postoperative respectively were 0.82 +/- 0.12, 0.36 +/- 0.04, 0.05 +/- 0.01, 0.03 +/- 0.01, 1.25 +/- 0.22, there were statistically significant differences between preoperative and postoperative (P < 0.05). According to Majeed scoring to evaluate the clinical function, postoperative pain, standing, sitting, sexual life, work ability, total score respectively were 22.54 +/- 4.02, 27.93 +/- 5.46, 8.47 +/- 3.61, 2.54 +/- 1.33, 16.46 +/- 4.34, 81.32 +/- 8.73, 60 cases got excellent results, 17 good, 3 fair. The main complications including fracture nonunion of 5 cases,deep incision infection of 1 case, and screw prominence resulting uncomfortable of 8 cases.

CONCLUSIONIliolumbar fixation has the advantages of stable fixation, satisfactory functional rehabilitation, less complications, and is a good method in treating sacrum fracture of Denis type II.

Adolescent ; Adult ; Bone Screws ; Female ; Fracture Fixation, Internal ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Sacrum ; injuries ; surgery ; Spinal Fractures ; surgery ; Treatment Outcome ; Young Adult

Aortic Aneurysm, Abdominal ; surgery ; Endovascular Procedures ; adverse effects ; Humans ; Intestinal Fistula ; diagnosis ; etiology ; Male ; Middle Aged

Aged ; China ; Health Status ; Humans ; Life Expectancy ; Life Tables

Objective To evaluate the relationship between hippocampal cyclic adenosine monophosphate response element-binding protein(CREB)/brain-derived neurotrophic factor(BDNF)signaling pathway and cognitive dysfunction in rats with chronic pathological pain.Methods Thirty-two healthy adult male Sprague-Dawley rats,weighing 220-250 g,were divided into 3 groups using a random number table:control group(group C,n=8),sham operation group(group S,n=8)and chronic pathological pain group(group CP,n=16).Chronic pathological pain model was established by injecting cobra venom 0.4 mg(4 μl)into the sheath of the infraorbital nerve.The mechanical pain threshold was measured at 3 days before establishment of the model(baseline)and 4 days and 1,2,3,4 and 8 weeks after establishment of the model.Morris water maze test was performed to evaluate the spatial learning and memory abilities at 5 and 9 weeks after establishment of the model.Eight rats were sacrificed at 5 and 9 weeks after establishment of the model in CP group,and rats were sacrificed after the end of Morris water maze test at 9 weeks after establishment of the model in C and S groups.The hippocampi were isolated for determination of the expression of phosphorylated CREB and BDNF in the hippocampal tissues using Western blot.Results Compared with group C,the mechanical pain threshold was significantly decreased at each time point after establishment of the model,the escape latency was prolonged at 5 and 9 weeks after establishment of the model,the rate of time of staying at the target quadrant was decreased,the frequency of crossing the original platform was decreased,and the expression of phosphorylated CREB and BDNF was down-regulated at 9 weeks after establishment of the model in group CP(P<0.05),and no significant change was found in the parameters mentioned above in group S(P>0.05).Conclusion The mechanism underlying cognitive dysfunction may be related to inhibited activation of CREB/BDNF signaling pathway in the hippocampus of rats with chronic pathological pain.

Objective To evaluate the analgesic effect of curcumin on trigeminal neuralgia in rats. Methods Thirty healthy adult male Sprague?Dawley rats, weighing 200-250 g, aged 7-8 weeks, were divided into 3 groups ( n=10 each) using a random number table: sham operation group ( group S) , tri?geminal neuralgia group (group TN) and trigeminal neuralgia + curcumin group (group Cur). Trigeminal neuralgia model was established by injecting cobra venom solution into the sheath of the infraorbital nerve ( ION) . Starting from 15 days after establishment of the model, curcumin 45 mg∕kg was intragastrically ad?ministered twice a day for 28 consecutive days in group Cur, while the equal volume of peanut oil was ad?ministered in group TN. Before establishment of the model (baseline), and on 4, 7, 14, 21, 28, 35 and 42 days after establishment of the model, the mechanical pain threshold was measured, the free behav?iors were observed, and the time and frequency of face?grooming and exploratory behaviors were recorded. After observation of the free behaviors, the ION and medulla oblongata on the affected side were removed for examination of the ultrastructure using transmission electron microscopy. Results Compared with group S, the mechanical pain threshold was significantly decreased, the time of face?grooming behaviors was signifi?cantly prolonged, the frequency of face?grooming behaviors was significantly increased, the time of explora?tory behaviors was significantly shortened, and the frequency of exploratory behaviors was significantly de?creased on 4-42 days after establishment of the model in group TN (P<0.05 or 0.01). Compared with group TN, the mechanical pain threshold was significantly increased, and the time of face?grooming behav?iors was significantly shortened on 28-42 days after establishment of the model, and the frequency of face?grooming behaviors was significantly decreased, the time of exploratory behaviors was significantly pro?longed, and the frequency of exploratory behaviors was significantly increased on 21-42 days after estab?lishment of the model in group Cur ( P<0.05 or 0.01) . Microscopic examination revealed that the changes in demyelination of the ION and medulla oblongata were significantly attenuated in group Cur as compared with group TN. Conclusion Intragastrically administered curcumin 45 mg∕kg ( twice a day for 28 consecutive days) can attenuate trigeminal neuralgia in rats, and the mechanism is related to the attenuated changes in demyelination of the ION and medulla oblongata.

Objective To evaluate the effect of curcumin on cognitive dysfunction in a rat model of trigeminal neuralgia.Methods Thirty healthy adult male Sprague-Dawley rats,weighing 200-250 g,were randomly divided into 3 groups (n=10 each) using a random number table:sham operation group (Sham group),trigeminal neuralgia group (TN group),and trigeminal neuralgia + curcumin group (TN + Cur group).Trigeminal neuralgia was produced by injecting cobra venom solution 4 μl into the sheath of the infraorbital nerve in TN and TN + Cur groups.Starting from 15 days after establishment of the model,1.5 ml peanut oil was injected through a gastric tube into stomach twice a day (in the morning and at night) for 28 consecutive days in TN group,and curcumin 45 mg/kg (dissolved in 1.5 ml peanut oil) was injected through a gastric tube into stomach twice a day (in the morning and at night) for 28 consecutive days in TN + Cur group.The cognitive function was assessed using Morris water maze test after the end of treatment.The escape latency,swimming speed,ratio of time of staying at the target quadrant,and the number of times the animals crossing the platform were recorded.The pathological changes in the hippocampal CA1 region were observed with an electron microscope.The ultrastructure of neurons,organelles and synapses in the hippocampal CA1 region was examined with a transmission electron microscope.Results There was no significant difference in the swimming speed between the three groups (P＞0.05).Compared with Sham group,the escape latency on 1st-4th days was significantly prolonged,the ratio of time of staying at the target quadrant was decreased,and the number of times the animals crossing the platform was decreased in TN group,and the escape latency was significantly prolonged on 3rd and 4th days in TN + Cur group (P＜0.01).Compared with TN group,the escape latency on 2nd-4th days was significantly shortened,the ratio of time of staying at the target quadrant was increased,the number of times the animals crossing the platform was increased (P＜0.01),and the pathological changes of hippocampal tissues were attenuated in TN + Cur group.Conclusion Curcumin can improve cognitive dysfunction in a rat model of trigeminal neuralgia.

Central nervous system (CNS) diseases are serious threats to human health. Blood-brain barrier (BBB) plays an important role in protecting the CNS. However, it also impedes the delivery of drugs to CNS and affects the treatment of CNS diseases. Brain targeted nano-drug delivery systems provide the possibility to brain-targeting drug delivery. In this article, we introduce the physiological structure and functions of BBB, and the brain targeting mechanism and the applications of brain-targeting nano-vectors to give a brief overview of the research status of brain targeting nano-drug delivery system.

Objective: To explore the molecular mechanisms of 14-3-3ζ in gemcitabine resistance in extranodal NK/T-cell lymphoma, nasal type (ENKTL) . Methods: The effects of cell proliferation and invasion were detected by cell counting kit-8 (CCK-8) assay and transwell assay. YTS cells were exposed to gradually increased concentrations of gemcitabine to establish gemcitabine-resistant YTS cells (YTS-gem) in vitro. 14-3-3ζ specific siRNA lentiviral vector was transfected into YTS and YTS-gem cells to downregulate 14-3-3ζ expression, and stable transfected cell clones were screened. The protein expression was determined by Western blot. Results: ①14-3-3ζ expression was significantly up-regulated in gemcitabine resistant YTS-gem cells, comparing with that of YTS cells (P<0.05) . ②The results of CCK-8 and transwell assay showed that downregulation of 14-3-3ζ significantly reduced the cell proliferation and invasion abilities (P<0.05) . ③Downregulation of 14-3-3ζ could restore gemcitabine sensitivity in gemcitabine resistant YTS-gem cells (P<0.05) . ④Western blotting results showed that knockdown of 14-3-3ζ significantly upregulated pro-apoptotic Bax, and downregulated anti-apoptotic Bcl-2, Caspase-3, cleaved caspase-3, Cyclin D1 in gemcitabine-resistant YTS-gem cells (P<0.05) . There was no significant difference in p53 ang P-gp expression levels. Conclusions: 14-3-3ζ was upregulated in gemcitabine resistant YTS cells. Overexpression of 14-3-3ζ promoted cell proliferation and enhanced cell migration. 14-3-3ζ contributed to gemcitabine resistance to ENKTL through anti-apoptosis.
14-3-3 Proteins/metabolism* ; Cell Line, Tumor ; Deoxycytidine/therapeutic use* ; Drug Resistance, Neoplasm ; Humans ; Lymphoma, Extranodal NK-T-Cell/drug therapy* ; Gemcitabine

The anti-apoptotic members of Bcl-2 family proteins, Bcl-2 and Mcl-1, are considered therapeutic targets of various cancers. In this article, we developed four hydrophobic tag (HyT)-based protein degraders of Bcl-2/Mcl-1, based on a Bcl-2/Mcl-1 dual inhibitor S1-6, and tested their capability in Bcl-2/Mcl-1 degradation and apoptotic induction in MCF-7 cells. Interestingly, different linkers in the HyT degraders led to selective Bcl-2/Mcl-1 degradation, though the degraders S1-D1-S1-D4 maintained the pan-Bcl-2 family binding capacity. Among them, S1-D2 and S1-D4, two compounds bearing a hydrophobic linker or a PEG linker, were observed to potently and selectively induce the ubiquitination and proteasomal degradation of Bcl-2 and Mcl-1 in living cells, with a degradation rate of more than 80% or 60%, respectively. Moreover, the HyT-based degraders showed increased lethality of cancer cells compared to the parent inhibitor S1-6, demonstrating that the advantage of degraders to the occupancy-based inhibitors.