Objective To observe the expression of fractalkine (FKN or CX3CL1) in serum and lung tissue in early phases after paraquat (PQ) poisoning in rats,and to analyze the effect of FKN on acute lung injury induced by PQ.Methods A total of 66 SD rats were randomly (random number) divided into two groups,namely PQ group (n =36) and control group (n =30).Through intra-peritoneal route,PQ (22 mg/kg) was administered to PQ group,and an equal volume of normal saline to control group instead.Rats were separately sacrificed at 6 h,12 h,24 h,72 h and 120 h after poisoning.Lung coefficient was determined.The levels of FKN in serum and lung tissue homogenate were detected by ELISA.Lung pathological changes were observed by HE staining.FKN changes were investigated by immunohistochemistry staining.Data was analyzed by SPSS 19.0.Results From 6 h to 120 h after poisoning,parameter determined in PQ group had great changes,compared with the control group.At 6 h,12 h,24 h,72 h and 120 h,lung coefficients in PQ group were 5.03 ±0.07,5.17 ±0.10,5.46 ±0.10,5.68 ±0.15 and 5.83 ±0.11,respectively,which were significantly higher than those (4.49 ± 0.20,4.28 ± 0.13,4.45 ± 0.17,4.31 ±0.19 and 4.31 ±0.16) in control group (P＜0.01).Levels of FKN (pg/mL) in serum were 140.9 ± 15.8,157.9 ± 17.6,188.8 ± 24.8,224.4 ± 18.1 and 229.9 ± 10.0,respectively,significantly higher than those (121.7 ± 12.8,121.6 ± 12.1,118.3 ± 14.0,122.8 ± 12.4 and 120.5 ± 8.8) in control group (6 h P ＜0.05,others P ＜0.01).Levels of FKN (pg/mL) in lung tissue homogenate were 4 222.0 ± 641.1,5 021.0 ± 514.5,5 911.6 ± 478.1,7 092.2 ± 652.9 and 7 639.3 ± 666.6,respectively,significantly higher than those (2 860.2 ± 477.3,3 068.9 ± 446.0,3 168.7 ± 728.5,3 178.0 ±488.2 and 3 147.3 ±426.6) in control group (P ＜0.01).In PQ group,pathological changes manifested themselves in inflammatory cell infiltration,congestion,edema,structural damage,etc.The lung injury aggravated gradually from 6 h to 120 h.In control group,there was no significant change.FKN expressed mainly in bronchial cells,alveolar epithelial cells and pulmonary artery endothelial cells.Where there was higher expression of FKN,there were more inflammatory cells infiltrated.The level of FKN in lung tissue homogenate was positively correlated with lung coefficient (r =0.937).The level of FKN in serum was positively related to that in lung tissue homogenate (r =0.968).Conclusion There is correlation between FKN and acute lung injury induced by PQ in rats.

Objective To observe the effect of superoxide dismutase ( SOD ) , malondialdehyde ( MDA ) , glutathione (GSH), catalase (CAT) and endothelin (ET-1) and tumor necrosis factor alpha (TNF-α) on rat renal tissue under acute hypoxia .Methods 24 male Wistar rats, weight 180~220 g, were randomly divided into control group and acute hypobaric hypoxia group .Acute hypoxia group was divided into 2 groups hypoxia 1 and hypoxia 2, 8 rats for each group.After acute hypobaric hypoxia 10min and 24h, rats were sacrificed.The left removed kidneys were analyzed for biochemical indexes , and the right parts were observed by immunohistochemistry to evaluate the expression level of renal endothelin (ET-1) and tumor necrosis factor alpha (TNF-α).Results After acute hypobaric hypoxia , the activity of SOD of the rats kidney was greatly decreased (P <0.01), CAT activity of hypoxia group 1 was significantly decreased (P <0.01), GSH activity of hypoxia group 2 was significantly decreased (P <0.05), but the MDA content had no obvious change ( P >0.05).The immunohistochemical staining showed that , the expression level of ET-1 and TNF-αwas increased remarkably, but it was reduced after 24 h.Conclusion The obviously decreased activity of SOD , CAT, GSH and significantly increased expression of ET-1 and TNF-α, may be involved in the pathogenesis of renal hypoxic injury .

Objective:Comparing the effect of different doses of simvastatin in lowering the serum lipid.Methods:79 patients were randomized into group A and group B,and were given simvastatin 10 mg*d-1 (group A) and 20 mg*d-1 (group B),respectively for a total of 8 weeks.Results:Comparing with baseline,in group A,TC,TG,LDL-C were decreased by 23.4%,20.0% and 30.7%,respectively (P＜0.01); HDL-C was increased by 17.5%.The content of serum TC,TG and LDL-C was decreased to the normal range in 12.8%,28.2% and 15.4% of the patients in group A.For the group B,TC,TG,LDL-C were decreased by 32.7%,22.8% and 42.8%,respectively (P＜0.01); HDL-C was increased by 13.7%.The content of serum TC,TG and LDL-C was decreased to the normal range in 65.0%,57.5% and 65.0% of the group B patients.Conclusion:Oral intake of 20 mg of simvastatin once a day can effectively reduce the serum lipid.The patients can well tolerate and no obvious side effect was observed in our study.

Objective To study the correlations between bone fracture types and healing time in patients with osteofluorosis. Methods Thirty-seven patients with osteefluorosis and long tubular bone fracture were diagnosed in accordance with radiogram retrospectively. The fractures were divided into two groups: sclerotic and osteoporotic. Twenty four fractured patients with non osteofluorosis were included in the study as controls. All of the patients had operation(open reduction and nickelclad internal fixation). Fracture healing in patients with sclerotic and osteoporotic groups was compared with the control group after operation. Results There were notable differenees(F=4.30,P< 0.05) in term of fracture healing time among the three groups [sclerotic group:(18.4±5.3)weeks; osteoporotic group: (24.5±5.1)weeks; control group: (17.6±3.8)weeks]. Notably, there were significant differences between the osteoporotic and control groups(q=2.34,P<0.05), and between sclerotic and osteoporotic gronps(q=2.51, P<0.05). The healing time of the osteoporotic group was longer than that of sclerotic group. The constituent ratios of fracture healing in sclerotic, osteoporotic and control groups were 73.1% (19/26) ,54.5% (6/11),75.0% (18/24) respectively, and the differences among the three groups were statistically significant(X2=3.67,P<0.05). The healing rate of the osteoporotic group was lower than that of sclerotic and control groups(X2=3.12, 3.36, all P< 0.05). The constituent ratios of healing in the sclerotic, osteoporotic and control groups were 26.9% (7/26),45.5% (5/11),25.0%(6/24), respectively, and there differences among the three groups were statistically significant (X2=4.07 ,P<0.05). The delayed healing rate of the osteoperotic group was higher than those of the sclerotic and control groups(X2= 3.87,3.95, all P<0.05). Conclusions Fracture healing time of osteoporotic osteofluorosis after fracture is longer than normal, and the cause might be the loss of bone mass.

OBJECTIVE:To investigate the effects of Tongxinluo capsules on inflammatory cytokines of mice with diabetic pe-ripheral neuropathy. METHODS:40 KK/Upj-Ay mice were randomly divided into model group(pure water),and Tongxinluo low, medium and high dose groups [1,2 and 4 g (medicinial materials)/kg]. 10 C57BL/6 mice were selected into the control group (pure water). The drugs were given once a day for consecutive 12 weeks,ig. The pain perception threshold,motor nerve conduc-tion velocity(MNCV)and sensory nerve conduction velocity(SNCV)were detected for the mice 1 h after the last administration of drugs. The flow cytometry was used to detect the levels of tumor necrosis factor α(TNF-α),interleukin-1β(IL-1β),cyclooxy-genase 2(COX-2)and monocyte chemoattractant protein 1(MCP-1)in serum. Real-time fluorescent quantitative polymerase chain reaction(RT-PCR)and Western blot were respectively employed to detect the mRNA and protein expressions of TNF-α,IL- 1β, COX-2 and MCP-1 in the mice’s sciatic nerves. RESULTS:Compared with control group,pain perception threshold in model group was decreased;MNCV and SNCV were slowed;the levels of TNF-α,IL-1β,COX-2 and MCP-1 in serum were increased;the expressions of mRNA and protein of TNF-α,IL-1β,COX-2,MCP-1 were increased,with significant differences(P<0.01 or P<0.05). Compared with model group,pain perception threshold in Tongxinluo medium and high dose groups were increased;MNCV and SNCV were increased;the levels of TNF-α,IL-1β,COX-2 and MCP-1 in serum were decreased;the expressions of mRNA and protein of TNF-α,IL-1β,COX-2,MCP-1 in sciatic nerves were decreased;the expressions of mRNA of COX-2, MCP-1 and protein of IL-1β,COX-2,MCP-1 in sciatic nerves in Tongxinluo low dose group were decreased,there were statistical significant difference(P<0.01 or P<0.05). CONCLUSIONS:Tongxinluo capsules have certain protective effects on the mice with peripheral nerve in case of diabetes by a mechanism that may be associated with the inhibition of inflammatory cytokines.

Aim To investigate the effects of Tongxin-luo capsule on oxidative stress in diabetic peripheral neuropathy (DPN )mice and its mechanisms.Meth-ods KK/Upj-Ay mice were divided into model, Tongxinluo low-dose group, Tongxinluo middle-dose group and Tongxinluo high-dose group.C57BL/6 mice were selected as control group.Mice were given drugs intragastrically for 12 weeks.Paw withdrawal latency, motor nerve conduction velocity (MNCV)were detec-ted.Activity of superoxide dismutase (SOD),gluta-thione peroxidase (GSH-Px)and content of malondial-dehyde (MDA)in blood were detected by colorimetric method.The expression of heme oxygenase-1 (HO-1 ),γ-glutamyl cysteine synthetase (γ-GCS ) of sciatic nerve was examined by real time PCR and Western blot.The protein expression of p38 MAPK,p-p38 MAPK,JNK,p-JNK,ERK,p-ERK was examined by Western blot.Results Compared with model group, paw withdrawal latency was increased and MNCV was faster in Tongxinluo group (P <0.05 ,P <0.0 1 ). SOD and GSH-Px contents significantly increased, MDA content decreased (P <0.01 ).HO-1,γ-GCS mRNA and protein expression significantly increased (P<0.05,P <0.01 )in Tongxinluo group.p-p38 MAPK protein expression decreased in Tongxinluo group (P<0.05 ).Conclusion Tongxinluo can in-hibit oxidative stress in DPN of mice via suppressing the phosphorylation of p38 MAPK.

Aim To explore the effect of genetic poly-morphisms of POR on the stable warfarin maintenance doses in Han Chinese patients receiving mechanical heart valve replacement. Methods The association between POR gene polymorphisms and warfarin doses of 185 Han Chinese patients were investigated through ANOVA or t test. SNPs of POR and VKORC1 were de-tected by Sequenom? DNA MassArray genotyping method. CYP2C9*3 was genotyped by polymerase chain reaction-restriction fragment length polymorphism method ( PCR-RFLP ) . Patients ’ clinical characteris-tics, INR value and daily dose were obtained from their medical records. Statistical analysis was performed by SPSS 21. 0 software. Results No mutant carriers of POR rs17148944 , POR rs56256515 and rs72553971 were found in this study. The genotype frequencies of other SNPs were in accordance with Hardy-Weinberg e-quilibrium. In the group of patients with CYP2C9*1*1 , the mutant type carriers ( T carriers ) of POR rs17685 had a significantly higher dose than CC carri-ers(3. 50 ± 1. 07) mg·d-1 vs (3. 14 ± 0. 94) mg· d-1,P =0. 03. Also, in the group of patients with CYP2 C9*1*1 and VKORC1 rs9934438 G allele carri-ers, the mutant type carriers ( T carriers ) of POR rs17685 had a significantly higher dose than CC carri-ers(4. 76 ± 0. 90) mg·d-1 vs (4. 08 ± 1. 03) mg· d-1 ,P=0. 04. No significant difference was found in different genotypes of POR rs2868177 . Conclusion These results illustrate that POR rs17685 T carrier is closely associated with a higher warfarin maintenance dose, suggesting that this SNP is useful for clinical guidance of warfarin.

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.

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 observe the effects of an enriched environment (EE) on cognitive functioning and the synaptic plasticity of mice modeling post-stroke cognitive impairment (PSCI) and explore the possible mechanisms involved.Methods Mice modeling PSCI and sham-operated mice were randomly divided into 3 groups:sham-operated mice in a standard environment (the Sham+SE group),PSCI mice in a standard environment (the PSCI+SE group) and PSCI mice in an enriched environment (the PSCI+EE group).The cognitive functioning of all of the mice was quantified using a Morris water maze and their hippocampal long-term potentiation (LTP) was recorded using an electrophysiological method.The level of synaptophysin was detected using Western blotting.Synaptic ultrastructure in the hippocampus was imaged using electron microscopy.Results Compared with the Sham +SE group,the PSCI+SE group showed significantly poorer water maze performance and failed induction of contralateral LTP.Their average level of synaptophysin was significantly lower,and significant adverse changes in the synaptic ultrastructure of the hippocampus were observed,including a decreased number of synapses.The average width of the synaptic cleft,postsynaptic density and the interface curvature of the synapses were all less desirable.All of the measurements of the PSCI+EE group improved significantly compared to those of the PSCI+SE group,but were still significantly poorer than those of the Sham+SE group.Conclusions An enhanced environment can improve the cognitive functioning of mice modelling PSCI.It may be that an EE can improve synaptic plasticity in the hippocampus contralateral to the stroke.