Multi-target drugs attract increasing attentions for the therapy of complicated neurodegenerative diseases. In this study, a computer-assisted strategy was applied to search for multi-target compounds by the pharmacophore matching. This strategy has been successfully used to design dual-target inhibitor models against both the acetylcholinesterase (AChE) and poly (ADP-ribose) polymerase-1 (PARP-1). Based on two pharmacophore models matching and physicochemical properties filtering, one hit was identified which could inhibit AChE with IC50 value of (0.337 +/- 0.052) micromol x L(-1) and PARP-1 by 24.6% at 1 micromol x L(-1).
Acetylcholinesterase ; metabolism ; Cholinesterase Inhibitors ; pharmacology ; Computer-Aided Design ; Drug Discovery ; methods ; Poly(ADP-ribose) Polymerase Inhibitors

Objective To investigate the value of electromagnetic navigation in microsurgical resection of intracranial cavernous hemangioma of different locations.Methods The microsurgical resection of intracranial cavernous hemangioma of different locations with the guide of electromagnetic navigation of COMPASS Cygnus system,There were 47 cavernous hemangioma of 43 patients,including of multiple cavernous hemangioma of 3 cases,one case had 3,the other 2 cases had 2 ; Including 25 deep in the cerebral cortex(including of 4 deep in the cerebellar cortex),twenty shallow in the cerebral cortex,two were in the orbital apex,including of 4 deep in the sensorimotor cortex,four deep in the language center,and 2 deep in the visual center.Results All 47 cavernous hemangioma of 43 patients,the accuracy was 100％.The resection rate was 100％,including of 16 patients were removed with a straight incision.There was no one with the neurological dysfunction worse postoperative,with no deaths,with 1 case of normal perfusion pressure breakthrough and was cured by conservative treatment.Thirty cases were discharged within 1 week.The blood loss of 30 cases was less than 50 ml.The average registration error of navigation was 1.6 ± 0.4 mm.Conclusion The surgical incision and surgical approach can been designed with the help of electromagnetic navigation system before operation,and can accurately resect the lesions simultaneously avoid brain function area,protect the normal brain tissue,reduce postoperative complications,with the help of the electromagnetic navigation system intraoperative in real time.It is suitable for minimally invasive surgery for intracranial cavernous hemangioma.

Objective To investigate the metabolite features of acute necrotizing pancreatitis in rats in vitro by high resolution magic angle spinning nuclear magnetic resonance spectroscopy (HR-MASNMR).Methods A total of 30 Wistar rats were randomized into ANP group ( n = 20) and control group ( n = 10).All the rats in ANP group were injected with L-arginine 2.5mg/g body weight twice, and the animals in the control group received same dose of saline. HR MASNMR was used to study the metabolic changes of acute necrotizing pancreatitis in rats in vitro. Results 12 hours after the ANP induction, the pancreas were more swelling, presented with bleeding points, with mild increase in liquefied change, coagulation necrosis could be found in parenchyma and a large number of fatty tissues could be seen around the pancreas. Serum amylase level was ( 3527 ± 429 ) U/L, which was significantly higher than ( 1250 ± 188 ) U/L in control group.Compared with those in the control group, the signal intensity of taurine ( Tau), acetic acid ( Ace), alanine (Ala) of the ANP group were significantly increased. While the signal intensities of phosphocholine (Pc),glycerophosphocholine (GPc) and betine (Bet) were significantly decreased. The signal intensities of choline (Cho), glutamic acid (Glu), lactate (Lac) were not significantly different. Conclusions There were obvious metabolic features of pancreatic tissues of ANP in rats, and it is useful for the application of magnetic resonance spectroscopy in AP in vivo in human studies.

Objective To evaluate the diagnostic value of the metabolic parameters for differentiating focal autoimmune pancreatitis (F-AIP) and pancreatic cancer (PC) by dual time 18F-FDG PET/CT scan.Methods Ten F-AIP patients and 20 PC patients in Changhai Hospital from May 2011 to November 2014 were enrolled in this study.All the AIP patients were histological confirmed or diagnosed by clinical follow up.The PC patients were histological confirmed and gender-and age-matched with F-AIP patients.50％ SUVmax was set as the threshold to fine-tune the boundary of interest.The extracted parameters included SUV SUV metabolic tumor volume (MTV),total lesion glycolysis (TLG),target-to-background ratio (TBR) and the retention indexes(RI) of all the parameters above.The PET/CT imaging features were also observed.Results The high metabolic lesions were observed in both F-AIP patients and PC patients.There were 6 F-AIP patients whose lesion was located in pancreas head,4 F-AIP patients whose lesion was located in pancreas body and tail.There were 12 PC patients whose lesion was located in pancreas head,8 PC patients whose lesion was located in pancreas body and tail.In F-AIP patients,2 cases had dilated pancreatic duct,6 had dilated biliary duct,8 had increased metabolism in mediastinal lymph node and 2 had abdominal lymphadenopathy,which were 8,5,5 and 14 cases in PC patients.The positive rate of mdeiastinal lymphadenopathy in F-AIP patients was statistically higher than that in PC patients,while the positivity rate of abdominal lymphadenopathy in AIP patients was lower than that in PC patients.The difference was statistically significant (both P ＜ 0.05).There were no statistical differences on the positivity rate of the dilated pancreatic duct,intra-and extra-hepatic bile duct between two groups.SUVmax,SUVmean and MTV in F-AIP were 5.37 ± 0.88,3.48 ± 0.66,21.79 ±15.60 in early stage and 6.45 ±1.51,4.23 ± 1.10,19.36 ± 14.63 in delayed stage,and those in PC were 8.31 ±3.08,5.41±1.95,9.26±8.35 in early stage,and 9.75±3.86,6.36±2.56,9.09±10.71 in delayed stage.SUVmax and SUVmean in F-AIP were lower than those in PC,whereas MTV were larger in F-AIP than that in PC.ROC curves for SUVmax,SUVmean and MTV were made.The AUC of SUV was the highest at 0.85,the cut-off value was 4.45,the corresponding sensitivity was 65％ and the specificity was 90％.TLG,TBR and RI of all the parameters were not statistically different in F-AIP and PC.Conclusions The 18F-FDG PET/CT metabolic parameters,such as SUVmax,SUVmean,MTV,could be of special diagnostic significance in discriminating F-AIP from PC.

OBJECTIVETo investigate the features and causes of complications of unilateral pedicle screw fixation combined with contralateral percutaneous translaminar facet screw fixation and lumbar interbody fusion in treating lower lumbar diseases.

METHODSThe clinical data of 166 patients with lower lumbar diseases who underwent unilateral pedicle screw fixation combined with contralateral percutaneous translaminar facet screw fixation and lumbar interbody fusion with intervertebral cages from January 2008 to December 2013 were retrospectively analyzed. There were 64 males and 102 females, aged from 24 to 74 years with a mean of 51.9 years old, suffered from lower lumbar lesions for 47.5 months on average (ranged, 8 months to 30 years). Among these patients, lumbar intervertebral disc degeneration was found in 49 patients, recurred lumbar intervertebral disc protrusion in 17 patients, massive lumbar intervertebral disc protrusion in 23 patients, lumbar intervertebral disc protrusion accompany with spinal canal stenosis in 27 patients, lumbar degenerative spondylolisthesis with degree I (Meyerding grade) in 21 patients, far lateral lumbar intervertebral disc protrusion in 5 patients. Single segmental diseases occurred in 124 patients and two segmental diseases in 42 patients. The diseases occurred at L(3,4) segment in 6 patients, at L(4,5) segment in 97 patients, at L5S1 segment in 21 patients, at L(2,3), and L(3,4) segments in 1 patient, at L(3,4) and L4,5) segments in 26 patients, and at L(4,5), and L5S1 segments in 15 patients.

RESULTSThere was no abnormal bleeding in the patients and no patient received blood transfusion. During the surgery, spinal dura mater injury with cerebrospinal fluid leakage complicated in 1 patient, a fracture of vertebral pedicle in 4 patients, and end plate injury in 2 patients. No postoperative cerebrospinal fluid, incision infection and skin necrosis were found after operation. Nerve root injury was found in 1 patient. According to the position of pedicles crew, 371 screws of 163 patients were in degree I and 3 screws of 3 patients were in degree II; position of translaminar facet screw, 199 screws of 157 patients were type I, 8 screws of 8 patients were type II, 1 screw of 1 patient was III. Translaminar facet screw was slightly short in 2 patients. Five patients were lost to follow-up, two patients were died. The remaining patients were followed up for 35.4 months on average (ranged, 12 to 60 months). During the follow-up period , end plate was cut off and intervertebral cages were embedded in 14 segments of 14 patients. Abnormal pain of both lower extremities was found in 1 patient. With the exception of 11 unidentified segments in 11 patients, 189 segments of 148 patients obtained intervertebral fusion. No loosening, displacement, breakage of pedicle screw or translaminar facet screw, displacement of intervertebral cages or obvious degeneration of adjacent segments were found. The coronal and sagittal planes balance of lumbar vertebra were obviously improved. Postoperative JOA score was significantly increased than that of preoperative.

CONCLUSIONUnilateral pedicle screw fixation combined with contralateral percutaneous translaminar facet screw fixation and lumbar interbody fusion with intervertebral cages is a good choice for the treatment of lower lumbar diseases, but it has a risk of complications. Abundant surgeon's surgical experience, careful operation, and rational use of imaging technique can effectively reduce the incidence of complications.

Adult ; Aged ; Bone Plates ; Female ; Humans ; Internal Fixators ; Intervertebral Disc Degeneration ; surgery ; Intervertebral Disc Displacement ; surgery ; Lumbar Vertebrae ; surgery ; Male ; Middle Aged ; Pedicle Screws ; Retrospective Studies ; Spinal Fusion ; Spondylolisthesis ; surgery ; Treatment Outcome ; Young Adult

Objective To observe the metabolic characteristics of an experimental model of chronic pancreatitis,and to investigate its role in the grading of chronic pancreatitis.Methods Thirty-six Wistar rats were injected with dibutyltin chloride (DBTC) solution (8mg/kg) via the tail vein to establish the experimental model of chronic pancreatitis.The 36 rats were divided into 6 groups with 6 rats in each group.On0,7,14,21,28,35 days after modeling,rats was sacrificed and pancreatic tissue of the rats was harvested,and a small part was used for pathologic study,the majority part was kept at-80℃ under liquid nitrogen freezing.Metabolites of pancreatic tissue were determined by high-resolution magic angle spinning nuclear magnetic resonance spectroscopic (HR-MAS NMRS).On the basis of the abnormal structure,tubular complexes,gland atrophy,fibrosis,edema and inflammatory cell infiltration,chronic pancreatitis was graded.Results Pathologic study showed the severity of chronic pancreatitis gradually increased with time after modeling.The 7th,14th day after modeling,the pancreatic change was mild chronic pancreatitis; the 21st,28th,35th day,the pancreatic change was changed into severe chronic pancreatitis.Principal component analysis of HR-MAS NMRS showed that the betaine (Bet) and choline ( Cho)-contained components were significantly increased in severe chronic pancreatitis; while aspartate (Asp),lactate (Lac),isoleucine/leucine/valine (I/L/V) and fatty acid (FA) were significantly reduced when compared with those in mild chronic pancreatitis and normal pancreatic tissue.There was no significant difference in the amount of metabolic characteristics between mild chronic pancreatitis and normal pancreatic tissue.Conclusions HRMAS NMRS was helpful in distinguishing the severe chronic pancreatitis from mild chronic pancreatitis.

OBJECTIVETo investigate the chemical constituents from the branch of Broussonetia papyrifera.

METHODColumn chromatographic methods were used to isolate the chemical constituents. ESI-MS and NMR methods were employed for their structural elucidation.

RESULTSix compounds were isolated and identified as (2S)-7, 3'-dihydroxy-4'-methoxyflavan (1), ergosterol peroxide (2), D-galacitol (3), sulfuretin (4), liriodendrin (5), graveolone (6), respectively.

CONCLUSIONCompounds 1-6 were isolated from the plant for the first time.

Benzofurans ; chemistry ; isolation & purification ; Broussonetia ; chemistry ; Ergosterol ; analogs & derivatives ; chemistry ; isolation & purification ; Flavonoids ; chemistry ; isolation & purification ; Furans ; chemistry ; isolation & purification ; Glucosides ; chemistry ; isolation & purification ; Plant Stems ; chemistry ; Plants, Medicinal ; chemistry

OBJECTIVETo observe the efficacy on primary osteoporosis treated with spreading moxibustion for warming yang and activating blood circulation so as to provide the effective clinical therapeutic methods for osteoporosis.

METHODSSixty cases of primary osteoporosis were randomized into a spreading moxibustion group (30 cases) and a calcium tablet group (30 cases). In the calcium tablet group, caltrate was prescribed for oral administration, 600 mg per day. In the spreading moxibustion group, on the basis of the treatment as the calcium tablet group, the spreading moxibustion was applied at Dazhui (GV 14) to Yaoshu (GV 2) for warming yang and activating blood circulation. The duration of treatment was 12 weeks. Visual analogue scale (VAS) score, TCM clinical symptom score and bone mineral density (BMD) were observed and compared before and after treatment in the patients between the two groups.

RESULTSVAS scores were reduced apparently after treatment in the two groups (both P < 0.01) and the results in the spreading moxibustion group were obviously superior to that in the calcium tablet group (2.36 +/- 0.43 vs 4.52 +/- 0.35, P < 0.01). BMD were all increased in the two groups (P < 0.05, P < 0.01) and the results in the spreading moxibustion group were superior to those in the calcium tablet group (both P < 0.05). The total clinical effective rate was 86.67% (26/30) in the spreading moxibustion group, apparently better than 63.33% (19/30) in the calcium tablet group (P < 0.05). TCM clinical symptom scores after treatment were all reduced apparently in the two groups (both P < 0.01), and the result in the spreading moxibustion group was obviously superior to that in the calcium tablet group (4.72 +/- 1.90 vs 6.82 +/- 2.30, P < 0.01). The total effective rate of TCM symptoms was 93.33% (28/30) in the spreading moxibustion group, apparently better than 70.00% (21/30) in the calcium tablet group (P < 0.05).

CONCLUSIONThe combined therapy of spreading moxibustion for warming yang and activating blood circulation and the oral administration of caltrate apparently relieves pain and TCM clinical symptoms, improves BMD in the patients of osteoporosis and achieves definite clinical efficacy in the patients of osteoporosis.

Aged ; Blood Circulation ; Bone Density ; Female ; Humans ; Male ; Middle Aged ; Moxibustion ; Osteoporosis ; physiopathology ; therapy ; Yang Deficiency ; physiopathology ; therapy

OBJECTIVETo measure the stability of Evans procedure and Chrisman-Snook technique in the treatment of II degree lateral collateral ligament of ankle joint, and provide basis for treatment and prognosis.

METHODSFrom July 2008 to June 2009,18 frozen corpes were collected, including 10 males and 8 females, with an average age of fresh 39.3 +/- 11.2 years. The frozen corpes were randomly divided into three group, including normal controls(group A), Evans procedure (group B) and Chrisman-Snook technique ( group C), 6 specimens in each group. Anterior talofibular ligament and calcaneofibular ligament were cut off to cause II degree lateral collateral ligament in group B and C. Evans procedure or Chrisman-Snook technique were applied to restore lateral collateral ligament, and measure biomechnics. The displacement of tibiotalar joint and subtalar joint were observed.

RESULTS(1) The lateral stress results of tibiotalar joint showed the displacement by Evans procedure (group B) was greater than other groups (P < 0.0001). There were no significant differences between group A and C (P > 0.05). (2) The lateral stress results of subtalar joint showed the displacement by Evans procedure (group B) was greater than other groups (P< 0.0001). There were no significant differences between group A and C (P > 0.05).

CONCLUSIONAnkle instability is caused by ankle joint lateral collateral ligament injury. Chrisman-Snook technique is better than Evans procedure in stability on the early stage of ankle joint restoration, and conform to principle of biomechanics.

Adult ; Ankle Joint ; Biomechanical Phenomena ; Female ; Humans ; Lateral Ligament, Ankle ; diagnostic imaging ; injuries ; surgery ; Male ; Mechanical Phenomena ; Prognosis ; Radiography ; Reconstructive Surgical Procedures ; methods

Objective At present,there is still a lack of effective means for the treatment of diabetic cystopathy,and to find natural antioxidants for this purpose has become a hot spot in research. This study is to investigate the protective effect of inosine on the bladder of diabetic rats and its antioxidative stress mechanisms. Methods A total of 60 adult male Sprague-Dawley rats were ran-domly divided into three groups of equal number:normal control,diabetes mellitus(DM) model control,and inosine intervention. The DM model was made by intraperitoneal injection of streptozotocin at 60 mg/kg. The DM model controls were injected with saline while the model rats in the intervention group with inosine, all at 75 mg/kg, ip,bid. After 4 and 8 weeks of treatment, the bladder tissues were collected from the rats for examination of the structural changes by HE staining,determination of the expressions of c-kit and nerve growth factor (NGF) by immunofluorescence assay, and observation of the ultrastructure of the bladder tissue under the electron microscope,de-tection of the cell apoptosis by TUNEL,and measurement of the con-tents of malondialdehyde (MDA),superoxide dismutase (SOD),and glutathione (GSH). Results HE staining indicated signifi-cant mucosal hyperplasia, disordered arrangement, loose structure, fracture, expanded intervals and collagen fiber filling of muscle bundles,muscular atrophy,lymphocytes infiltration,vascular hyperplasia and congestion,and few muscle bundles,while electron mi-croscopy manifested disordered arrangement, interrupted connection, mitochondrial vacuolation in muscular and interstitial cells, shrinkage of nuclear membrane,disappearance of nucleoli,and irregular chromatin margination and condensation in the bladder tissues of the DM rat models. Immunofluorescence assay showed that the signals of c-kit and NGF were reduced in the DM models as compared with those in the normal controls. After 4 and 8 weeks of intervention,the cell apoptosis rate was significantly higher in the DM model control ([1.68±3.04]% and [10.51±0.90]%) and inosine-treated rats ([7.00±1.72]% and [7.24±1.66]%) than in the normal controls ([4.65±3.04]% and[5.48±2.00]%),but remarkably lower in the inosine-treated than in the DM model controls(P<0.01). The contents of SOD and GSH were increased(P<0.05) while that of MDA decreased markedly in the DM models(P<0.05),but the former decreased (P<0.05) while the latter increased significantly in the inosine intervention group as compared with the DM model control group (P<0.05). At 8 weeks,the contents of SOD and GSH were remarkably lower in the DM model than in the normal con-trols (P<0.01),while that of MDA markedly higher than in both the normal control and inosine intervention groups (P<0.01). The wet weight of the bladder was significantly increased in the DM model and inosine intervention groups in comparison with that of the nor-mal controls(P<0.01). Conclusion Oxidative stress plays an important role in the development and progression of diabetic cystopa-thy. Inosine can protect the bladder structure and function of the DM rat by reducing oxidative stress and injury to the bladder tissue.