BACKGROUND:Antedor canulated screw has been considered an ideal method to treat odontoid fracture.OBJECTIVE:To compare the biomechanical properties of different anterior screws.DESIGN,TIME AND SETTING:A randomized contrast study was performed at the Biomechanics Laboratory of Southern Medical University from March to September 2006.MATERIALS:Double-thread canulated screws and single-thread canulated screws were made of titanium alloy and provided by Shuangyang Medical Apparatus Co.,Ltd.,Suzhou.METHODS:A total of head-neck complexes (C0-C3) which were collected from 20 corpses were maintained in formaldehyde for less than 3 months;thereafter,the muscles and ligaments were removed to obtain the axis specimens so as to make type Ⅱ odontoid fracture models.The fracture samples were individually treated with double-thread and single-thread canulated screws,with 10 samples for each group.MAIN OUTCOME MEASURES:The shear stiffness and the maximum resistance of the two kinds of screw were tested in this study.RESULTS:The shear stiffness of the double-thread screw group was significantly higher than the single-thread screw group (P＜0.01 );however,there was no significant different in the maximum resistance between the two groups (P＞0.05).CONCLUSION:Double-thread canulated screws have a strong biomechanical stability for treating odontoid fracture;therefore,the first choice of the internal fixation should be double-thread canuiated screws for patients with osteoporosis or those who are susceptible to expanded screw pathway during surgical procedures.

OBJECTIVETo investigate the feasibility of no nasogastric intubation and early oral feeding at will after thoracolaparoscopic esophagectomy for patients with esophageal cancer.

METHODSBetween January 2013 and January 2014, the feasibility of no nasogastric intubation and early oral feeding at postoperative day(POD) 1 after thoracolaparoscopic esophagectomy was prospectively investigated in 156 patients (trial group) with esophageal cancer in the Henan Cancer Hospital. One hundred and sixty patients previously managed in the same unit who were treated routinely after thoracolaparoscopic esophagectomy were served as control group.

RESULTSOf 156 patients of trial group, 6(3.8%) patients could not take food early as planned because of postoperative complications. The overall complication rate in trial group was 19.2%(30/156), which was 25.0%(30/160) in control group (P=0.217). The anastomotic leakage in trial group and control group was 2.6%(4/156) and 4.3%(7/160) respectively (P=0.380). Compared with control group, time to first flatus [(2.1±0.9) d vs. (3.3±1.1) d, P<0.001], bowel movement [(4.4±1.3) d vs. (6.6±1.0) d, P<0.001] and postoperative hospital stay [(8.3±3.2) d vs. (10.4±3.6) d, P<0.001] were significantly shorter in trial group.

CONCLUSIONSNo nasogastric intubation and early oral feeding postoperatively in patients with thoracolaparoscopic esophagectomy is feasible and safe. This management can shorten postoperative hospital stay and fasten postoperative bowel function recovery.

Eating ; Esophageal Neoplasms ; surgery ; Esophagectomy ; Fasting ; Feasibility Studies ; Humans ; Intubation, Gastrointestinal ; Postoperative Complications ; Postoperative Period

Objective:To compare the accuracy of two methods in reducing leg length discrepancy(LLD)during hip hemiarthroplasty.Methods:We retrospectively analyzed 89 patients of hip hemiarthroplasty who suffered from femoral neck fracture.There were 47 patients in the new method group(NM), and 42 patients in the traditional method group(traditional method, TM)which comparing the position of the greater trochanter tip and the center of the femoral head.In the NM group, the distance from the center of femoral head to the lesser trochanter(L)and the diameter of femoral head(D)of the healthy side hip were measured on preoperative anteroposterior pelvic X-ray film, and the ratio(R)of D to L was calculated.During operation, the diameter of the femoral head(d)was measured with a caliper, and the distance should be obtained from the center of the femoral head prosthesis to the lesser trochanter according to the ratio R of the healthy side.The difference of postoperative LLD between the two groups and the incidences of |LLD| in each range were compared.Results:In the NM group, the maximum LLD was 11.10 mm and the minimum LLD was -4.0 mm, with an average of(4.4±3.2)mm, 80.9%(38/47)| LLD | < 6 mm, 93.6%(44/47)| LLD | < 10 mm, 6.4%(3/47)| LLD | ≥ 10 mm.In the TM group, the maximum LLD was 13.2 mm and the minimum LLD was -8.3 mm, with an average of (6.2±5.1)mm, 42.9%(18/42)|LLD|<6 mm, 69.0%(29/42)|LLD| <10 mm, 31.0%(13/42)|LLD|≥10mm.The differences of patients of the mean postoperative LLD and the incidences of |LLD| in each range between two the groups were statistically significant( t=-2.036、 χ2=14.629, P=0.046、0.001). Conclusions:The new method is simple, convenient, more accurate and can obtain a more satisfactory LLD compared with the traditional method which refers to the relative position of the great trochanter tip and the center of the femoral head.

Objective:To explore the roles and mechanisms of metformin in the improvement of cognitive dysfunction induced by chronic cerebral hypoperfusion in rats.Methods:Total 82 SD male rats (SPF grade) aged 3-4 months were randomly divided into four groups: sham operation control group (Con group, n=15), sham operation with metformin treatment group (Met group, n=20), 2-vessel occlusion group (2VO group, n=22), and 2-vessel occlusion with metformin administration group (2VO+ Met group, n=25). The chronic cerebral hypoperfusion model was established by bilateral common carotid artery ligation, and the carotid arteries of rats in Con group and Met group were only separated without ligation.After 2VO operation, rats in 2VO+ Met group and Met group were given metformin solution in drinking water at a dose of 100 mg/kg per day for 4 weeks.After 4-week continuous intervention with metformin, Morris water maze was performed to test the spatial cognitive function of the rats, in vivo electrophysiological technology was used to detect the long-term potential of the rats, and enzyme-linked immunosorbent assay(ELISA) was used to detect the concentrations of inflammatory factor tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) and interleukin-6(IL-6) in the hippocampus.The density of dendritic spines of hippocampal neurons was observed by Golgi staining, and the synaptic structure of hippocampal neurons, especially the vesicle density, was observed by transmission electron microscopy.SPSS 16.0 software was used for statistical analysis.Repetitive measurement ANOVA was used for the escape latency data of 7 days repeated learning training in water maze.One-way ANOVA was used for the comparison of other data among multiple groups, and Dunnett's t test was used for further pairwise comparison. Results:Morris water maze results showed that during 7 days of learning training, the time and group interaction for escape latency was not significant in the 4 groups of rats ( F=0.93, P>0.05), but the time main effect ( F=25.90, P<0.05) and group main effect ( F=13.20, P<0.05) were significant.Morris water maze test showed that from the 3rd to 7th day, the escape latencies in 2VO group were significantly longer than those in Con group and 2VO+ Met group(all P<0.05). The short-term memory of rats was detected after 1 day of rest.The results showed that the escape latency in 2VO group was significantly longer than that in Con group and 2VO + Met group( P<0.01). The retention time and crossing times in the platform area of 2VO rats were less than those in Con group and 2VO + Met group ( P<0.01). Electrophysiological results showed that the relative field excitatory postsynaptic potential slope of 2VO group (1.29±0.09) was significantly lower than that in Con group (2.07±0.09) and 2VO + Met group (1.69±0.08)( P<0.01). ELISA results showed that TNF-α level in hippocampal tissue of 2VO group was significantly higher than that in Con group and 2VO+ Met group; IL-1β and IL-6 levels in hippocampal tissue of 2VO group were significantly higher than those in Con group and 2VO + Met group.Density of dendritic spines in hippocampal neurons of 2VO group was significantly lower than that in Con group and 2VO+ Met group.The density and proportion of immature dendritic spines in hippocampal neurons of 2VO group were significantly higher than those in Con group and 2VO + Met group.Synaptic vesicle density of neurons in CA1 area of hippocampus in 2VO group ((230.29±19.44) vescicles/μm 2) was significantly lower than that in the Con group ((414.52±13.17) vescicles/μm 2) and 2VO+ Met group ((313.19±12.42) vescicles/μm 2). Conclusion:Metformin can reduce neuroinflammation of hippocampus with chronic cerebral hypoperfusion and improve synaptic plasticity and cognitive dysfunction.It may have potential application value in the treatment of vascular cognitive dysfunction.

Objective:To explore the protective effects and mechanisms of L-carnitine (LCAR) on cognitive dysfunction in chronic cerebral hypoperfusion rats.Methods:Totally 90 SD male rats (SPF class) aged 3-4 months were divided into four groups according to random number talbe: sham operated control group (SHAM group, n=15), sham operated with L-carnitine treatment group (LCAR group, n=25), 2-vessel occlusion group (2VO group, n=25), and 2-vessel occlusion with L-carnitine treatment group (2VO+ LCAR group, n=25). The chronic cerebral hypoperfusion model was established by bilateral common carotid artery ligation, and the carotid arteries from SHAM group and LCAR group were only separated without ligation.L-carnitine was administered intraperitoneally (300 mg·kg -1·d -1) for 30 days after surgery in the LCAR and 2VO+ LCAR groups.After 30 days of L-carnitine intervention, Morris water maze was performed to test the spatial cognitive function of the rats, the ATP level of hippocampal tissue was detected by chemiluminescence, the mitochondrial structure and synaptic structure of hippocampal neurons were observed by transmission electron microscopy, the degree of mitochondrial damage was scored, the vesicle density was counted and measured, the level of N-methyl-D-aspartate receptor subunit 2A or 2B(NR2A/B) and postsynaptic density 95(PSD95) in hippocampal tissue were detected by Western blot.The expression and distribution levels of transcription factor cAMP response element-binding protein(CREB) in brain tissues were observed by immunofluorescence.SPSS 16.0 software was used for statistical analysis.The escape latency data of repeated learning training in Morris water maze was conducted by repetitive measurement ANOVA, while other data were adopted by one-way ANOVA, and Dunnett's t test was used for further pairwise comparison. Results:(1)Morris water maze results showed that the time and group interaction of escape latency was not significant among the 4 groups of rats ( F=1.4, P>0.05), but the time main effect and group main effect were significant( F=21.6, 15.2, both P<0.05). Morris water maze results showed that platform position learning from 3rd to 7th day, the escape latencies in 2VO group were longer than those in SHAM group and 2VO+ LCAR group (all P<0.05). The results of short-term memory showed that the escape latency in 2VO group was longer than those in SHAM group and 2VO+ LCAR group (all P<0.05). Meanwhile, the retention time and crossing times in the platform area of 2VO group were less than those in SHAM group and 2VO+ LCAR group (all P<0.05). (2) The absolute and relative levels of ATP in hippocampus showed that the difference among the 4 groups were statistically significant ( F=14.6, 13.2, both P<0.05). ATP level of hippocampus in 2VO group was lower than those in SHAM group and 2VO+ LCAR group (both P<0.05). Electron microscopic observation of mitochondrial morphology showed that the Flameng score of mitochondrial damage in the hippocampus of rats in 2VO group (2.82±0.17) was higher than those in SHAM group (0.25±0.07) and 2VO+ LCAR group (1.76±0.09) (both P<0.05). (3) The density of synaptic vesicles in the hippocampus of rats in 2VO group ((289.09±22.41)/μm 2)was lower than those in SHAM group ((497.49±28.89)/μm 2)and 2VO+ LCAR group ((401.23±45.09)/μm 2) (both P<0.01). Western blot results showed that the relative levels of synaptic proteins NR2A/B, PSD95 and CREB in 2VO group were lower than those in SHAM group and 2VO+ LCAR group (all P<0.05). Immunofluorescence results showed that the relative level of CREB expression in hippocampal subregions and cortex in 2VO group was lower than those in SHAM group and 2VO+ LCAR group (both P<0.01). Conclusion:L-carnitine can improve spatial learning and memory dysfunction in rats with chronic cerebral hypoperfusion, which are related with promoting ATP production and protecting mitochondrial morphology, and promoting synaptic vesicle synthesis and synaptic protein expression.

Bromodomain containing protein 4 (BRD4), as an epigenetic reader, can specifically bind to the acetyl lysine residues of histones and has emerged as an attractive therapeutic target for various diseases, including cancer, cardiac remodeling and heart failure. Herein, we described the discovery of hit 5 bearing 4-phenylquinazoline skeleton through a high-throughput virtual screen using 2,003,400 compound library (enamine). Then, structure-activity relationship (SAR) study was performed and 47 new 4-phenylquinazoline derivatives toward BRD4 were further designed, synthesized and evaluated, using HTRF assay set up in our lab. Eventually, we identified compound C-34, which possessed better pharmacokinetic and physicochemical properties as well as lower cytotoxicity against NRCF and NRCM cells, compared to the positive control JQ1. Using computer-based molecular docking and cellular thermal shift assay, we further verified that C-34 could target BRD4 at molecular and cellular levels. Furthermore, treatment with C-34 effectively alleviated fibroblast activation in vitro and cardiac fibrosis in vivo, which was correlated with the decreased expression of BRD4 downstream target c-MYC as well as the depressed TGF-β1/Smad2/3 signaling pathway. Taken together, our findings indicate that novel BRD4 inhibitor C-34 tethering a 4-phenylquinazoline scaffold can serve as a lead compound for further development to treat fibrotic cardiovascular disease.