AIM: To investigate the effect of dexmedetomidine (DEX) on renal injury induced by lung ischemia/reperfusion (I/R) in mice and its relationship with endoplasmic reticulum stress response.METHODS: Healthy SPF male C57BL/6J mice, weighing 20~24 g, aged 8~10 weeks, were randomly divided into 5 groups (n=10 each): sham operation group (sham group), I/R group, atipamezole (Atip) group, DEX group, and DEX+Atip group.In vivo lung I/R model was established by occlusion of the left pulmonary artery for 30 min followed by 180 min of reperfusion in the mice.The Atip (250 μg/kg), DEX (20 μg/kg) and DEX+Atip were intraperitoneally infused into the mice before left pulmonary hilus was blocked in Atip group, DEX group and DEX+Atip group, and other operations were the same as I/R group.After experiment, the mice were killed, and the renal tissues were harvested to observe the morphological changes.The enzymatic activity of caspase-3, serum creatinine and blood urea nitrogen, and cell apoptotic index of the renal cells were also analyzed.The expression of c-Jun N-terminal kinase (JNK), caspase-12, CCAAT/enhancer-binding protein homdogous protein (CHOP) and glucose-regulated protein 78 (GRP78) at mRNA and protein levels in the renal tissues was determined by RT-PCR and Western blot.RESULTS: Compared with sham group, the enzymatic activity of caspase-3, serum creatinine and blood urea nitrogen, renal cell apoptotic index, and the mRNA and protein levels of JNK, caspase-12, CHOP and GRP78 in I/R group were significantly increased (P<0.01), and the renal tissues had obvious damage under light microscope.Compared with I/R group, Atip group and DEX+Atip group, the enzymatic activity of caspase-3, serum creatinine and blood urea nitrogen, renal cell apoptotic index, and the mRNA and protein levels of JNK, caspase-12 and CHOP in DEX group were significantly decreased, and the expression level of GRP78 significantly increased (P<0.01).Furthermore, the renal tissue damage was obvious reduced.CONCLUSION: DEX effectively relieves the renal injury induced by lung I/R in mice, which may be associated with exciting α2-adrenergic receptor and inhibiting endoplasmic reticulum stress response.

Artemisinin and its derivatives have shown the potential application value in anti-tumor fields.But their applications are limited due to poor solubility, short half-life and so on;therefore, many scholars devoted themselves to developing and studying relative pharmaceutical preparations.Nano drug delivery system is a new drug delivery tool.Compared with the traditional dosage forms, such as tablets, suppositories and injections, nano drug delivery system has such advantages as good stability, targeted drug release and combined drug delivery.In this review, nano drug delivery carriers for artemisinin were summarized, including nanoparticles, liposomes, micelles, nanomicroemulsions and so on.The research results and characteristics of artemisinin-containing nano formulas in tumor therapy, as well as the co-delivery system of artemisinin and transferrin, were discussed.

Objective To evaluate dexmedetomidine-induced cardioprotection in a mouse model of lung ischemia-reperfusion (I/R) and the relationship with endoplasmic reticulum stress.Methods Forty healthy SPF male C57BL/6J mice,weighing 20-24 g,aged 8-10 weeks,were divided into 4 groups (n=10 each) using a random number table:sham operation group (Sham group),lung I/R group (I/R group),dexmedetomidine group (Dex group) and dexmedetomidine plus atipamezole (specific α2-adrenergic receptor antagonist) group (DA group).The model of lung I/R injury was established by clamping the left hilum of lung for 30 min followed by 180 min of reperfusion.In group Sham,only sternotomy was performed,the hilum of lung was not clamped,and the mice were mechanically ventilated for 210 min.In Dex and DA groups,dexmedetomidine 20 μg/kg and dexmedetomidine 20 μg/kg plus atipamezole 250 μg/kg were injected intraperitoneally,respectively,at 30 min before establishment of the model.At 180 min of reperfusion,blood samples were collected from the orbit for determination of creatine kinase-MB (CK-MB) and lactic dehydrogenase (LDH) activities in serum.The animals were then sacrificed,and hearts were removed for determination of apoptosis in cardiomyocytes (by TUNEL) and expression of phosphorylated c-Jun N-terminal kinase (p-JNK),caspase-12,CCAAT/enhancer-binding protein homologous protein (CHOP) and glucose-regulated protein 78 (GRP78) in myocardial tissues (by Western blot),and expression of JNK,caspase-12,CHOP,GRP78 mRNA in myocardial tissues (by real-time polymerase chain reaction).Apoptosis index was calculated.Results Compared with Sham group,the serum CKMB and LDH activities and apoptosis index were significantly increased,the expression of p-JNK,JNK mRNA,and caspase-12,CHOP and GRP78 protein and mRNA was up-regulated in I/R,Dex and DA groups (P＜0.01).Compared with I/R group,the serum CK-MB and LDH activities and apoptosis index were significantly decreased,the expression of p-JNK,JNK mRNA,and caspase-12 and CHOP protein and mRNA was down-regulated,the expression of GRP78 protein and mRNA was up-regulated in group Dex,and the expression of GRP78 protein and mRNA was significantly up-regulated (P＜0.01),and no significant change was found in the other parameters in group DA (P＞0.05).Compared with DEX group,the serum CK-MB and LDH activities and apoptosis index were significantly increased,the expression of pJNK,JNK mRNA,and caspase-12 and CHOP protein and mRNA was up-regulated (P＜0.01),and no significant change was found in the expression of GRP78 protein and mRNA in DA group (P＞0.05).Conclusion Dexmedetomidine can reduce myocardial injury induced by lung I/R,and the mechanism may be related to activation of α2-adrenergic receptors and inhibition of endoplasmic reticulum stress in myocardial cells of mice.

BACKGROUND:Operative approaches of lumbar interbody fusion include anterior (ALIF),posterior (PLIF) and transforaminal lumbar interbody fusion (TLIF).The resected structures and cage implantation sites are different,and the initial stability of lumbar spine is varied.OBJECTIVE:To compare the initial stability of lumbar spine following ALIF,PLIF or TLIF in combination with bilateral pedicle screw fixation.DESIGN:Comparative observation.MATERIALS:Fifteen samples of fresh calf lumbar spine were used.METHODS:Models ofALIE PLIF and TLIF were simulated.After examination as normal group,the samples were randomly divided into three groups (n=5).Besides anterior,posterior and transforaminal lumbar interbody fusion include anterior,bilateral pedicle screw fixation was performed.MAIN OUTCOME MEASURES:Biomechanical characteristics of the lumbar spine before and after ALIF,PLIF or TLIF in combination with bilateral pedicle screw fixation.RESULTS:Following three approaches of lumbar interbody fusion,the stability of lumbar spine was significantly reduced,which was enhanced after bilateral pedicle screw fixation (torsion indexes were also increased).In addition,rigidity of the lumbar spine was enhanced.The stability indexes of lumbar spine following TLIF were significantly greater than the other approaches,indicating the initial stability of TLIF was the best.The rigidity,stress,and swain of lumbar spine following PLIF were greater than ALIE but torsion indexes were smaller than ALIE CONCLUSION:The stability of lumbar spine following lumbar interbody fusion was significantly reduced compared with normal sample.But bilateral pedicle screw fixation greatly increases the stability.Among three types of lumbar interbody fusion,the initial stability of lumbar spine following TLIF is the best.

BACKGROUND:Transforaminal lumbar interbody fusion(TLIF)can be applied in any lumbar segment,and retain integrity of lateral vertebral plate and zygapophysiai joints.However,few studies have been conducted about the biomechanical performance.OBJECTIVE:To explore the stability of lumbar intervertebral segment following TLIF appHed bilateral and unilateral transpedicular screws fixation.DESIGN,TIME AND SETTING:Biomechanical test was performed at the Institute of Biomechanics,Shanghai University and Nantong University between August 2005 and April 2006.MATERIALS:Twenty samples of fresh one-month-old calf lumbar vertebra.METHODS:Twenty samples of calf lumbar vertebra underwent TLIF alone,TLIF in combination with bilateral or unilateral transpedicular screws fixation.Biomechanical test was performed on spinal three dimensional motion testing machine.MAIN OUTCOME MEASURES:Stress,displacement.strain and torsion angle were recorded.RESULTS:After TLIF without fixation.no obvious changes were found in mean stress and strain,but the axes stiffness and rotational stiffness were significantly decreased,indicating TLIF could produce immediate lumbar stability.After TLIF with unilateral or bilateral transpedicular screws fixation,the lumbar stability was significantly enhanced compared with TLIF alone,especially bilateral transpedicular screws fixadon.Although the lumbar stability following unilateral transpedicular screws fixation was inferior to bilateral fixation,it was still greatly enhanced,even bxceeded normal sample,indicating TLIF with unilateral transpedicular screws fixation could produce enough initiallumbar stability.CONCLUSION:TLIF alone cannot support sufficient initial stability,but TLIF with bilateral and unilateral transpedicular screws fixation can enhance lumbar initial stability.

Objective To assess the safety and efficacy of percutaneous nephrolithotripsy withpneumatic and ultrasonic power in pediatric renal calculi. Methods The clinical data of 44 patientstreated with combination of pneumatic and ultrasonic power during pereutaneous nephrolithotripsywere retrospectively analyzed. The 44 patients had 49 renal calculi. The patients were all under 14years old. The average age was 11 years (range 7-14 years). There were 39 unilateral and 5 bilateralcalculi. Among the 44 patients,metabolic disturbance occurred in 19 cases (43.2%),anatomical dys function occurred in 15 cases (34.1%),urinary tract infection occurred in 14 cases (31.8%). Ante grade percutaneous access was established under ultrasound guidance,a combination of pneumatic andultrasonic lithotripsy were used. The effect was evaluated by postoperative KUB and ultrasonic. Re suits The access was successfully established in all patients. Complete stone clearance was achievedin 36 kidneys in phase Ⅰ,stones from 9 kidneys were completely removed with second lithotripsy.Leftover stone in 2 kidneys were treated by ESWL. Open surgery was performed in 2 kidneys due toexcessive bleeding. The operative time ranged from 52 132 min,average time was 79 min. Two pa tients needed blood transfusion. No severe complications occurred in all patients. Thirty seven pa tients were followed up for 3 18 months. The renal function was not worsened and hydronephrosiswas not aggravated in these patients. Conclusion The percutaneous nephrolithotripsy with pneumatic and ultrasonic power is a safe,effective treatment for pediatric renal calculi.

Objective To observe the effects of Yiqi Huoxue Tongluo Jiedu fang (YHTJF) on pneumocyte apoptosis after lung ischemia/reperfusion (I/R) injury (LIRI) in mice and to investigate whether c-Jun N-terminal protein kinase (JNK) is involved in the mechanism of apoptosis.Methods Seventy C57BL/6J male mice were randomly divided into seven groups:normal control group (C group),carboxyl methyl cellulose-Na+normal control group (CMC-Na+C group),CMC-Na+sham group (CMC-Na+S group),CMC-Na+I/R group (CMC-Na+I/R group) and CMC-Na+YHTJF-low,-middle,-high dose groups (CMC-Na+YL,CMC-Na+YM,CMC-Na+YH groups).C group did not undergo any processing;in CMC-Na+S group,only was chest opened without clipping the lung hilum;in the rest of the four groups,they all underwent opening of the chest and clipping the lung hilum for 30 minutes,then the clipping of artery was relieved and left lung reperfusion was carried out for 3 hours.After operation,the mice were sacrificed,the lung tissues were harvested.Under light and electron microscopes,the lung morphological and ultra-structural changes were observed,and the changes of index of quantitative evaluation for alveolar damage (IQA) were determined.The terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) was applied to evaluate the apoptosis index (AI) of the lung tissues.The protein and mRNA expressions of JNK and glucose regulating protein 78 (GRP78) in lung tissues were detected by Western Blot and reverse transcription-polymerase chain reaction (RT-PCR);the correlations between lung AI and the expressions of mRNA and protein of JNK and GRP78,IQA were analyzed.Results Compared with CMC-Na+S group,IQA,AI and mRNA and the protein expressions of JNK and GRP78 in CMC-Na+I/R group were obviously higher [IQA:(74.00 ± 7.31)％ vs.(7.00 ± 1.23)％,AI:(64.40 ± 11.97)％ vs.(5.60 ± 1.14)％,JNK mRNA (gray value):1.143 ± 0.284 vs.0.152 ± 0.128,GRP78 mRNA (gray value):0.897 ± 0.129 vs.0.284 ± 0.044,JNK protein (A value):0.428 ± 0.074 vs.0.073 ± 0.052,GRP78 protein (A value):1.075 ± 0.145 vs.0.589 ± 0.060].Compared with CMC-Na+I/R group,the IQA,AI,protein and mRNA expressions of JNK and GRP78 in CMC-Na+YL,CMC-Na+YM,CMC-Na+YH groups were all lower,and the degree of reduction in group CMC-Na+YM was the most remarkable,greater than that in CMC-Na+YL or CMC-Na+YH group [IQA:(26.20 ± 3.35)％ vs.(34.00±5.34)％,(41.20±9.18)％,AI:(29.40±3.05)％ vs.(48.20±3.83)％,(39.20±6.14)％,JNK mRNA (gray value):0.681 ± 0.130 vs.0.804 ± 0.153,0.938 ± 0.11,GRP78 mRNA (gray value):0.450 ± 0.105 vs.0.747 ± 0.231,0.566 ± 0.115,JNK protein (A value):0.188 ± 0.049 vs.0.261 ± 0.065,0.209 ± 0.063,all P ＜ 0.01],compared with the CMC-Na+I/R group,the expression of GRP78 protein was obviously higher in CMC-Na+YH,CMC-Na+YL,CMC-Na+YM groups and the most remarkably high was in CMC-Na+YH group (A value:1.429 ±0.226 vs.1.130±0.169,1.128 ±0.177,all P ＜ 0.01).The apoptosis of each group was mainly in the pulmonary vascular endothelial cells and alveolar epithelial cells,and brown particles were positive cells under light microscope.Under transmission electron microscope:nuclear pyknosis and margination under the nuclear membrane,cytoplasm condensed,lamellar bodies decreased and emptying increased,cell membrane microvilli decreased or disappeared,mitochondria swelling,inflammatory cells increased in alveolar septum and adhering onto the capillary walls could be seen in CMC-Na+I/R group.Compared with CMC-Na+I/R group,the lung tissue ultrastructural damage alleviated,ultrastructure of alveoli clearly seen,nuclear chromatin relatively uniform,cytoplasm increased,type Ⅱ alveolar epithelial cell surface microvilli relatively plenty,lamellar corpuscle number increased,mitochondria swelling ameliorated in CMC-Na+YH,CMC-Na+YL,CMC-Na+YM groups and the most remarkable one was CMC-Na+YM group.AI was significantly positive correlated with the mRNA and protein expressions of JNK,GRP78 and IQA (r =0.907,0.928,0.880,0.712,0.911,all P ＜ 0.01).Conclusions YHTJF may effectively alleviate the cell apoptosis in mice LIRI,and its mechanism may be related to the inhibition of JNK pathway.

Background Mitomycin C (MMC) is still irreplaceable until now.While it's current administration method has proved less than effective in the treatment of refractory glaucoma.To construct a MMC sustained release system which can maintain effective concentration and reduce toxicity is important for postoperative scarring regulation after glaucoma filtration surgery.Objective To evaluate the postoperative effect of use PTMC-F127-PTMC thermosensitive hydrogel as a new drug delivery carrier to sustained release MMC in rabbit trabeculactory.Methods Sixty rabbits,aged 10 to 14 weeks,were divided into 5 trabeculectomy groups in accordance with the random number table,including surgery only group,blank PTMC-F127-PTMC group and three sustained groups with 0.1 ml PTMC-F127-PTMC loaded with 0.05,0.10,0.20 g/L MMC injected after surgery.The MMC concentration of anterior chamber aqueous in three sustained release group with 0.1 ml PTMC-F127-PTMC loaded with 0.05,0.1,0.2 g/L MMC injected after surgery were tested by Guangzhou Analysis and Testing Center using high performance liquid chromatograph-mass spectrometer (HPLC-MS).At 3,7 days postoperatively,0.1 ml aqueous humor from 2 random selected rabbits in each group was extracted using 1 ml syringe with 30G needles from corneal limbus.At postoperative 1,3,5,7,10,14,28 days,bleb width and depth were calculated with caliper measurements and height was graded semiquantitatively by slit-lamp examinations,intraocular pressure (IOP) was measured with Tonopen.And corneal endothelial cell densities were examined by corneal endothelial counting before and 28 days after surgery.Sequential sections of the operative region were prepared and stained with hematoxylin and eosin and proliferating cell nuclear antigen (PCNA) after taking off the eyeballs from dead rabbits at 28 days later.Results MMC could be sustained released from PTMC-F127-PTMC hydrogel for more than 20 days.The mean postoperative bleb survival time in trabeculectomy surgery only group,blank hydrogel group and three sustained release groups were (5.3 ± 0.4),(5.5 ± 0.4),(12.2 ± 1.0),(25.1 ± 0.9),(26.7 ± 0.7) days respectively,the difference between each group was significantly (F =123.200,P =0.000).0.05 g/L MMC sustained release group has a better bleb survival time than that of surgery only group and blank hydrogel group (P =0.000).Compared with other groups,0.10 g/L and 0.20 g/L MMC sustained group has the longest bleb survival time (P =0.000),and more obvious IOP downtrending (F=53 010.000,P＜0.01).But the difference between the two groups was not significant.There was no difference in cornea endothelia cells counts between each group and no MMC was detected in aqueous humors.Histopathology test shows that the inflammatory response and fibrosis were lighter in MMC sustained release group,with stronger proliferation inhibition.Conclusions PTMC-F127-PTMC thermosensitive hydrogel can be a new drug delivery carrier to sustained release MMC.Sustain release MMC can extent bleb survival time with low toxicity.

Objective To detect serum oxytocin and highly sensitive C-reactive protein (hs-CRP) levels in obese and type 2 diabetes mellitus(T2DM) subjects and investigate the relationships between serum oxytocin levels and hs-CRP, glycolipid metabolism, insulin resistance and pancreas β cell function. Methods A total of 176 subjects were enrolled in the study, including 88 patients with newly-diagnosed type 2 diabetes ( T2DM) and 88 subjects with normal glucose tolerance(NGT). NGT and T2DM groups were further divided each into normal weight (NW) and obese(OB) subgroups. Obesity was defined as body mass index(BMI)≥25 kg/ m2 according to the WHO-Western Pacific Region diagnostic criteria (2000). 75g oral glucose tolerance test ( OGTT) was performed in all subjects. Fasting plasma glucose ( FPG), 2 h postprandial plasma glucose (2hPG), fasting insulin ( FINS), 2h postprandial serum insulin(2hINS), HbA1C and lipids were also determined. Insulin resistance and pancreas β-cell function were determined by homeostasis model assessment ( HOMA-IR, HOMA-β). Highly sensitive C-reactive protein(hs-CRP) level was determined by chemiluminescence immunoassay and fasting serum oxytocin level was determined by ELISA. Results Serum oxytocin level was lower in T2DM group than that in NGT group(P<0. 01), while serum hs-CRP level was higher in T2DM group than that in NGT group(P<0. 01). The level of serum oxytocin in subjects with obesity was also lower than that in subjects with NW in both NGT and T2DM groups [7. 16(6. 45-8. 82) vs 7. 98(7. 03-9. 17) ng/ L and 9. 23(8. 16-10. 36) vs 9. 86(8. 77-12. 06) ng/ L, P<0. 05]. The level of serum hs-CRP in subjects with obesity was higher than that in subjects with NW in both NGT and T2DM groups [0. 99(0. 25-1. 97) vs 0. 54(0. 19-0. 91) mg/ L and 3. 47(1. 63-6. 20) vs 1. 65(0. 81-3. 81) mg/ L, P<0. 05]. Serum oxytocin level was negatively correlated with hs-CRP, BMI, WC, WHR, HbA1C , FPG, 2hPG, FINS, 2hINS, total cholesterol, triglycerides, LDL-C and HOMA-IR, while was positively correlated with HOMA-β(P<0. 05). Subjects within the upper serum hs-CRP tertile had lower level of oxytocin when compared to subjects in the middle or lower serum hs-CRP tertiles(P<0. 05 ). Conclusion Serum oxytocin level was decreased in subjects with type 2 diabetes as well as with obesity. Serum oxytocin level was closely correlated with inflammation, glycolipid metabolism, insulin resistance, and pancreas β cell function. It may play an important role in the pathogenesis of obesity and T2DM.

Objective: To investigate the analgesic mechanism of Tuina (Chinese therapeutic massage) by observing the effect of the N-methyl-D-aspartate receptor subunit 2B (NR2B)/postsynaptic density-95 (PSD-95) pathway on the dendritic structure of spinal cord dorsal horn in rats with lumbar disc herniation. Methods: Fifty Sprague-Dawley rats were randomly divided into a blank group, a model group, a Tuina group, a blocker agent group, and a blocker agent + Tuina group. The sciatic nerve chronic constriction injury (CCI) model was prepared by the sciatic nerve ligation method. From the 4th day after modeling, rats in the Tuina group and the blocker agent + Tuina group were subject to daily Tuina intervention, and those in the blocker agent group and the blocker agent + Tuina group were daily intrathecally injected with NR2B blocker agent (MK-801). The spontaneous pain score was used to observe the pain behavior of all rats. The expression levels of NR2B and downstream PSD-95 were measured by immunohistochemistry, and the dendritic structure changes were observed by Golgi staining for rat spinal cord dorsal horn after 14 d of continuous intervention. Results: Compared with the blank group, the degree of rat spontaneous pain after CCI was elevated in both the model and the Tuina groups (P<0.01) and was reduced in the Tuina group after the Tuina intervention compared with the model group (P<0.05). Compared with the model group, the rat spontaneous pain level after blocking NR2B was reduced in both the blocker agent group and the blocker agent + Tuina group (P<0.05). The NR2B and PSD-95 protein levels were significantly higher in the model group compared with the blank group (P<0.01); the total number of dendritic branches was increased (P<0.01), and the total dendritic length became longer (P<0.01) in the spinal cord dorsal horn. The rat NR2B and PSD-95 protein levels were significantly decreased in the Tuina group compared with the model group (P<0.01); the total dendritic branch number was reduced (P<0.01) and the total length was shortened (P<0.01) in the spinal cord dorsal horn. After blocking NR2B, the expression levels of NR2B and downstream PSD-95 protein were significantly lower in both the blocker agent group and the blocker agent + Tuina group compared to the model group (P<0.01). The total branch number was significantly reduced (P<0.01), and the total length was significantly shortened (P<0.01) of the dendrites in the spinal cord dorsal horn. Conclusion: Tuina may exert an analgesic effect by remodeling the dendritic structure in the spinal cord dorsal horn in rats with lumbar disc herniation, and its mechanism may be related to the inhibition of NR2B/PSD-95 signaling pathway.