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Recent studies have found that in the development of epilepsy, cyclic adenosine monophosphate response element binding protein (CREB) may cause recurrent epilepsy by inhibiting the expression of γ-aminobutyric acid, resulting in neuron damage and weakened effect of antiepileptic drug targets. Antiepileptic drugs can not control the extent or frequency of seizures, and then the patients are in a persistent state, hence the development of drug-resistant epilepsy. Therefore, the mechanism of CREB leading to drug-resistant epilepsy was reviewed in this paper, hoping to provide ideas for the treatment of drug-resistant epilepsy patients.
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Objective:To screen 89Zr-labeled anti-epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) monoclonal antibody molecular probes suitable for monitoring the gastric mucinous adenocarcinoma bearing mouse models with low glucose metabolism. Methods:The expression of EGFR and HER2 in the MGC803 gastric cancer cell line was verified by analyzing cell slides and xenograft tumor sections. 89Zr-Deferoxamine (DFO)-Cetuximab and 89Zr-DFO-Pertuzumab were prepared and the radiochemical purity was detected. Cell binding experiments and blocking experiments were performed to verify the binding ability and specificity of the probes. Twelve gastric mucinous adenocarcinoma bearing mouse models were divided into 3 groups ( n=4 in each group): 89Zr-DFO-Cetuximab group (7.4 MBq/mouse, 74 μg/mouse), 89Zr-DFO-Pertuzumab group (7.4 MBq/mouse, 70 μg/mouse) and 18F-fluorodeoxyglucose (FDG) group (7.4 MBq/mouse). MicroPET imaging was performed at 4, 24 and 48 h ( 18F-FDG group underwent imaging at 1 h only) post-injection. The biodistribution study of 89Zr-DFO-Cetuximab and 89Zr-DFO-Pertuzumab was conducted in 2 groups ( n=4 in each group) 48 h after the injection. The independent sample t test was used for data analysis. Results:The immunofluorescent staining demonstrated EGFR expression was significantly higher than HER2 expression in MGC803 gastric cancer cell line. The radiochemical purity of 89Zr-DFO-Cetuximab and 89Zr-DFO-Pertuzumab were both more than 95%, and the specific activities were 100 and 95 MBq/mg, respectively. The two probes had good stability in normal saline and fetal bovine serum, with the radiochemical purity higher than 80% at 72 h. MicroPET imaging showed that the uptake of 89Zr-DFO-Cetuximab in the MGC803 tumor was significantly higher than that of 18F-FDG and 89Zr-DFO-Pertuzumab. The biodistribution study demonstrated the 89Zr-DFO-Cetuximab uptake (percentage activity of injection dose per gram of tissue, %ID/g) of tumors at 48 h was significantly higher than that of 89Zr-DFO-Pertuzumab (56.3±12.0 vs 22.0±3.6; t=4.31, P<0.05). Conclusion:Compared with 89Zr-DFO-Pertuzumab, 89Zr-DFO-Cetuximab has a better potential for non-invasive monitoring of gastric mucinous adenocarcinoma with low glucose metabolism.
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Objective:To prepare a 68Ga labeled probe targeting integrin alpha M(CD11b) receptor, namely 68Ga-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid-Glycine-Arginine-Glutamate-Arginine-Glutamate-polyethylene glycol 11-1, 2, 4, 5-terazine/CD11b antibody-F(ab′) 2-trans-cyclooctene ( 68Ga-NOTA-Polypeptide-PEG 11-Tz/anti-CD11b-F(ab′) 2-TCO), and to explore its feasibility as a molecular probe for CD11b receptor through microPET imaging. Methods:Immunofluorescence was used to detect the expression of CD11b on the surface of RAW264.7 cell. CD11b specific monoclonal antibody (M1/70) was conjugated with TCO, and anti-CD11b-F(ab′) 2-TCO fragment was obtained. The ligand NOTA-Polypeptide-PEG 11-Tz was labeled with 68Ga, and its specific activity and radiochemical purity were detected. Pre-targeted cell binding experiment was conducted to evaluate the binding ability of molecular probe. CT26 colon cancer bearing mouse models were established, and then pre-targeted biodistribution and imaging experiments were performed. Immunohistochemical experiment was used to verify the expression of CD11b receptor in tumor. The one-way analysis of variance was used to compare the data. Results:The results of immunofluorescence demonstrated CD11b receptor was highly expressed on the surface of RAW264.7 cell. Anti-CD11b-F(ab′) 2-TCO fragment was verified by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). 68Ga-NOTA-Polypeptide-PEG 11-Tz was successfully synthesized, with the labeling efficiency of 94.6%. The specific activity was 7.0-7.4 MBq/μg, and the radiochemical purity was higher than 95%. Pre-targeted cell binding experiment confirmed that the molecular probe bound to the CD11b receptor. The biodistribution and imaging experiments showed that the kidney radioactivity uptake was high at pre-targeted 4, 12 and 24 h intervals, which proved that probe was excreted through the urinary system. In addition, molecular probe had higher radioactive uptake at the tumor site, with the tumor/muscle ratios of 9.23±1.45, 12.53±1.36 and 10.74±1.11 ( F=848.8, P<0.05). When the radioligand was injected 1 h after the pre-positioned 12 h interval, the images contrast was the best, with the standardized uptake value (SUV) in tumor and muscle of 0.67±0.12, 0.09±0.04, respectively. Immunohistochemistry verified the highly expression of CD11b receptor in tumor. Conclusions:The pre-targeted molecular probe 68Ga-NOTA-Polypeptide-PEG 11-Tz/anti-CD11b-F(ab′) 2-TCO is successfully synthesized. The molecular probe has targeting ability for CD11b + colon cancer, and is expected to be used as a tracer targeting CD11b receptor in vivo.
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Objective ToexplorethevalueofCTtargetreconstructionforpureground-glassnodules(pGGN)onidentifyingthe invasivenessofthelungadenocarcinoma.Methods ThepGGNs weredividedintopre-invasivegroup[atypicaladenomatoushyperplasia (AAH),andadenocarcinomainsitu(AIS)]andinvasivegroup[minimallyinvasiveadenocarcinoma(MIA),andinvasiveadenocarcinomas(IA)] accordingtothepathologicresults.ThemorphologicfeaturesofpGGNonCTincludedthelargestdiameters,CTvalue,pleuralindentation,air bronchogram,bubblelucency,vesselconvergence,vesseldilatation,lobulationandspeculation.Twodiagnosticiansevaluatedthemorphologic featuresofpGGNonCT.Binary L o g istic regressionwasusedtoassesstheassociationbetweenCTfindingsandhistopathological classification.ROCcurveanalysiswasusedindiameterandCTvalue.Results Betweenpre-invasiveandinvasivegroup,therewere significantdifferencesindiameter,CTvalue,spiculationandvesseldilatation(P<0.05).Nodifferencewasfoundinlobulated-margin,bubble lucency,airbronchogram,vascularconvergenceorpleuralindentationbetweenthetwogroups(P>0.05).Thediagnosticthresholds forpredictingpGGOinfiltrationwere8.75mminmaximumdiameterand-605HUinCTvaluerespectively.Conclusion ThepGGNwitha diametermorethan87.5mm,theCTvaluemorethan-605HU,andpresencesofspiculationandvesseldilatationsuggeststhatpGGOisinvasive.
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Ischemic stroke is a leading cause of morbidity and mortality worldwide. Resident microglia are the principal immune cells of the brain, and the first to respond to the pathophysiological changes induced by ischemic stroke. Traditionally, it has been thought that microglial activation is deleterious in ischemic stroke, and therapies to suppress it have been intensively explored. However, increasing evidence suggests that microglial activation is also critical for neurogenesis, angiogenesis, and synaptic remodeling, thereby promoting functional recovery after cerebral ischemia. Here, we comprehensively review the dual role of microglia during the different phases of ischemic stroke, and the possible mechanisms controlling the post-ischemic activity of microglia. In addition, we discuss the dynamic interactions between microglia and other cells, such as neurons, astrocytes, oligodendrocytes, and endothelial cells within the brain parenchyma and the neurovascular unit.
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Objective To explore the effect of primary exchange reamed nailing (ERN) and augmentation compression plating (ACP) combined with autogenous bone grafting (ABG) on health-related quality of life in patients with dystrophic or atrophic nonunion of femoral shaft after intramedullary nailing. Methods The study used a prospective study method. Sixty- two patients with femoral shaft nonunion after intramedullary nailing from August 2010 to October 2016 were selected, and the patients were divided into ERN group (group A, 32 cases) and ACP group (group B, 30 cases) by random digits table method. In group A, isthmus nonunion was in 18 cases (56.2％), and non-isthmus nonunion in 14 cases (43.8％); in group B, isthmus nonunion was in 16 cases (53.3％), and non-isthmus nonunion in 14 cases (46.7％ ). The health- related quality of life was compared between 2 groups, including physical component summary (PCS) and mental component summary (MCS) in the- 12- item short form health survey (SF- 12), brief pain inventory- severity (BPI- S) and brief pain inventory- interference (BPI- I). Results Fifty-four patients were followed-up for more than 1 year, and the mean follow-up time was 18.3 (13 to 37) months. All patients successfully achieved bone union, and the mean time was 5.8 (4 to 8) months. Significant improvements in terms of SF-12 PCS and SF-12 MCS score were noted after operation for patients with isthmus nonunion in both groups (t=3.148, 2.156, 2.456 and 2.559; P < 0.05), but there were no significant differences before and after operation in group A with non-isthmus nonunion (P >0.05). At the last follow-up, SF-12 PCS and SF-12 MCS in group B were significantly improved compared with those in group A: (45.2 ± 5.8) scores vs. (33.6 ± 4.7) scores and (48.8 ± 6.5) scores vs. (39.4 ± 5.6) scores, and there were statistical difference (P<0.05); SF-12 BPI-S and BPI-I showed obvious relief: (4.6 ± 2.1) scores vs. (6.2 ± 2.5) scores and (5.2 ± 1.9) scores vs. (6.8 ± 2.7) scores, and there were statistical differences (P<0.05); however there were no statistical difference in SF-12 PCS, SF-12 MCS, BPI-S and BPI- I between 2 groups (P>0.05). Conclusions Compared with ERN combined with ABG, ACP combined with ABG can significantly improve the quality of life in patients with dystrophic or atrophic nonunion of femoral shaft after intramedullary nailing. It has greater advantage on the improvement of health-related quality of life, especially for patients with non-isthmus nonunion.
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Objective To analyze the related risk factors of re-nonunion after primary revision for femoral shaft nonunion subsequent to failed intramedullary nailing. Methods A retrospective study was performed in 61 patients with femoral shaft nonunion subsequent to failed intramedullary nailing from June 2008 to June.All patients were divided into re-nonunion group(22 cases)and non-re-nonunion group (39 cases) according to diagnostic criteria of bone re-nonunion. Univariate analysis was used to analyze 14 factors that may lead to the occurrence of re-nonunion after revision for femoral shaft nonunion subsequent to failed intramedullary nailing including age, gender, body mass index (BMI), smoking, alcohol abuse, injury reason, fracture types, intramedullary nail types, locking screws technology for intramedullary nail, bone nonunion sites, bone nonunion time, pathological types of bone nonunion, primary revision methods and autologous bone graft or not, and multi-factor logistic regression analysis was performed on the factors showing a significant difference. Results Univariate analysis showed significant difference in smoking (χ2= 6.564, P = 0.036), BMI (χ2= 6.783, P = 0.021), bone nonunion sites(χ2=7.316,P=0.011),primary revision methods(χ2=8.069,P=0.003)and autologous bone graft or not(χ 2=6.668,P=0.027).Logistic regression analysis showed that primary revision methods(OR=1.027,95% CI 0.028-0.463,P<0.05)and autologous bone graft or not(OR=1.024,95% CI 0.006-0.363, P < 0.05) were independent risk factors for re-nonunion after revision of femoral shaft nonunion subsequent to failed intramedullary nailing. Conclusions Primary revision methods and autologous bone graft or not are independent risk factors for re-nonunion after revision of femoral shaft nonunion subsequent to failed intramedullary nailing.By strictly controlling the surgical indications and combining with autogenous bone grafting,it is possible to reduce the occurrence of nonunion after primary revision of the femoral shaft nonunion subsequent to failed intramedullary nailing.
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Objective To investigate the feasibility of low-dose CT perfusion imaging(CTPI)examination combined with iterative model reconstruction (IMR) in the brain.Methods 80 patients with clinical suspicion of acute cerebral infarction underwent the cerebral CTPI were enrolled in this study.30 normal hemispheres on group A [35 cases,80 kV,150 mAs, filtered back projection(FBP)] and group B(45 cases,80 kV,30 mAs, IMR) were selected to evaluate respectively.The pictures' subjective scores, effective radiation dose (ED),CT value,SD,signal to noise ratio(SNR), contrast to noise ratio(CNR) and the perfusion parameters of the grey matter (GM) and white matter(WM) in each hemisphere of the middle cerebral artery(MCA) territory were respectively compared at ASPECTS level 2 for the two groups.Results The ED were 2.52,0.50 mSv for group A,B.There were no statistical significances in the perfusion parameters,CT value, SD, CNR of the ROIs of the GM and WM,the SNR of the ROIs of the GM and the pictures' subjective scores between group A, B (P>0.05).There was statistical significance in the SNR of the ROIs of the WM between group A,B (P<0.05).Conclusion IMR combined with 30 mAs of the CTPI can reduce the radiation dose apparently while maintain the stability of the image quality and perfusion parameters.
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Objective To investigate the feasibility of iterative model reconstruction (IMR) combined with low tube voltage and low iodine intaken of contrast media in head and neck CT angiography (CTA). Methods Eighty patients with clinical suspicion of head and neck vascular disease underwent head and neck CTA were enrolled in this prospective study. According to random number table, patients were randomly divided into two groups. Group A (n=40) was scanned according to the protocol of 120 kV, 50 ml iopromide (370 mg/ml) and filtered back projection (FBP) reconstruction, and group B (n=40) was scanned with 80 kV, 30 ml iohexol (300 mg/ml) and IMR, while the other parameters kept consistent. Mann-Whitney U test was used to compare the enhanced CT value of arteries, image noise, signal noise ratio (SNR), contrast noise ratio (CNR), the score of image quality, effective radiation dose (ED) and iodine intaken of contrast media between two groups. Results The CT value at the origin level of common carotid artery were (316.9 ± 53.0) and (433.4 ± 101.8)HU in group A and B, image noise were (28.1 ± 6.8)and (12.1 ± 2.6)HU ,SNR were (11.9 ± 3.2) and (37.7 ± 13.3) ,and CNR were (10.2 ± 2.9) and (32.6 ± 13.3), respectively. There were showed significant differences in CT value, image noise, SNR and CNR between two groups (Z=-5.490,-7.592,-7.698,-7.660, P<0.05). The CT value at the origin level of internal carotid artery were (359.5 ± 54.3) and (443.5 ± 120.1) HU in group A and B, image noise were (18.8±6.2) and (6.8±1.7) HU ,SNR were 21.5±8.7 and 69.7±27.4 ,and CNR were 18.0±7.3 and 62.7± 26.4, respectively. The significant differences were acquired in CT value, image noise, SNR and CNR between two groups (Z=-3.022,-7.376,-7.496,-7.515, P<0.05). The CT value at M1 segment level of middle cerebral artery were (321.1±47.3) and (401.6±104.0) HU in group A and B, image noise were (32.3± 17.2) and (11.2 ± 2.7) HU,SNR were 12.4 ± 5.6 and 39.3 ± 18.4,and CNR were 10.7 ± 4.7 and 36.4 ± 17.7, respectively. There also showed significant differences in CT value, image noise, SNR and CNR between two groups (Z=-3.527,-7.487,-7.482,-7.535, P<0.05). The score of image quality of group A and B were 3.9 ± 0.7 and 4.5±0.6, which also showed significant difference between two two groups (Z=-3.517, P<0.05). The ED were (2.78 ± 0.13) and (0.84 ± 0.04) mSv for group A and B, which also showed significant difference between the two groups (Z=-7.706, P<0.05). The iodine intaken of contrast media were 1.85 g and 0.90 g in group A and B. Conclusion IMR combined with low tube voltage and low iodine intaken of contrast media can not only decrease effective radiation dose and iodine intaken of contrast media significantly, but also improve the imaging quality in head and neck CTA examination.
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Objective To analyze the related risk factors for Lisfranc injury resulting from low energy violence.Methods A retrospective study was performed for 61 cases (35 males,26 females) with low-energy foot injury hospitalized from June 2008 to June 2014.Mean age was 36.7 years (range,16-57 years).Fall injuries were noted in 24 cases,sports injuries in 21 cases,and twist injuries in 16 cases.The cases were divided into Lisfranc injury group(n =23) and non-Lisfranc injury group (n =38) according to the different diagnosis.Univariate analysis and multi-factor logistic regression analysis were used to identify the factors that may lead to the occurrence of Lisfranc injury including age,gender,body mass index,operation history,smoking,alcohol abuse,injury reason,medial depth of the mortise/ second metatarsal length (b/a),lateral depth of the mortise/ second metatarsal length (c/a),first metatarsal-to-talus angle,first intermetatarsal angle,second metatarsal length/foot length(a/g),calcaneal inclination angle and cuboid-navicular overlap/cuboid vertical height (e/e + f).Results Univariate analysis showed between-group differences were significant in age (x2 =7.385,P ＜0.05),injury reason (x2 =8.663,P ＜ 0.05),calcaneal inclination angle (t =3.958,P ＜ 0.05),b/a (t =5.051,P ＜ 0.05) and a/g(t =4.618,P ＜ 0.05).Logistic regression analysis identified b/a(OR =1.036,95 ％ CI 0.018-0.450,P ＜ 0.01) and a/g(OR =1.013,95％ CI 0.005-0.374,P ＜ 0.01) as independent risk factors for low-energy Lisfranc injury.Conclusion Low-energy Lisfranc injury is independently associated with b/a and a/g,and may relate to the decreased medial depth of the mortise and increased foot length.
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Objective To investigate the effects of protocadherin 20 (PCDH20) in the spinal cord in the development of bone cancer pain (BCP) in rats.Methods Thirty-six SPF female Sprague-Dawley rats,weighing 180-200 g,were randomly divided into 4 groups (n =9 each):sham operation group (group S),BCP group,lentivirus control group (group LC) and PCDH20 siRNA lentivirus group (group P).Control lentivirus and lentivirus containing PCDH20 siRNA 4 μl were injected into the ipsilateral spinal cord in groups LC and P,respectively.One week later,BCP was induced by injection of Walker 256 breast cancer cells into the upper segment of bone marrow of right tibia.The mechanical paw withdrawal threshold (MWT) was measured at 1 day before injection of lentivirus (T1),1 day before BCP (T2),and 7,14 and 21 days after BCP (T3-5).Three rats in each group were sacrificed after measurement of the MWT at 21 day after BCP and the tibia on the operated side was obtained for examination of invasion of the cancer cells with light microscope.The spinal cord was removed for determination of the expression of PCDH20 and postsynaptic density 95 (PSD95) protein (by Western blot) and mRNA (by RTPCR).Results In groups BCP,LC and P,the cancer cells grew out of the bone and destroyed the cortical bone seriously.Compared with group S,the MWT was significantly decreased at T3-5 in groups BCP,LC and P,the expression of PCDH20 and PSD95 protein and mRNA was up-regulated in groups BCP and LC,and the expression of PCDH20 was up-regulated in group P (P ＜ 0.05).Compared with BCP group,no significant change was found in the MWT and expression of PCDH20 and PSD95 protein and mRNA in group LC (P ＞ 0.05),and the MWT was significantly increased at T4,5 and the expression of PCDH20 and PSD95 protein and mRNA was down-regulated in group P (P ＜ 0.05).Conclusion PCDH20 is involved in the development of BCP through regulating the expression of PSD95 in the spinal cord and adjusting the function of excitatory synapse in rats.
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<p><b>BACKGROUND</b>Connexin 43 (Cx43) is one of the major components of human keratinocyte gap junctions. To study whether gap junctional intercellular communication participates in the transfer of acupoint signals and acupuncture analgesia, the expression of Cx43 was studied in Zusanli (ST36) acupoints compared with control non-acupoint regions in rats after acupuncture. In addition, Cx43 heterozygous gene knockout mice were used to further explore the relationship between Cx43 and acupuncture analgesia.</p><p><b>METHODS</b>The expression of Cx43 was detected by immunohistochemistry, immunoblotting, and RT-PCR for the Cx43 protein and mRNA. The influence of the Cx43 gene knockout on acupuncture analgesia was measured by a hot plate and observing the writhing response on Cx43 heterozygous gene knockout mice.</p><p><b>RESULTS</b>Immunohistochemistry showed abundant Cx43 expression in some cells in the skin and subcutaneous tissue of rat ST36 acupoints. The mRNA and protein levels of Cx43 in acupoints were significantly higher than those in the control points in the non-acupuncture group, and even more so after acupuncture. The hot plate and writhing response experiments showed that partial knockout of the Cx43 gene decreased acupuncture analgesia.</p><p><b>CONCLUSION</b>Cx43 expression and acupuncture analgesia showed a positive correlation.</p>
Subject(s)
Animals , Female , Mice , Rats , Acupuncture Analgesia , Acupuncture Points , Blotting, Western , Connexin 43 , Genetics , Metabolism , Gene Expression Regulation , Genotype , Immunohistochemistry , Mice, Knockout , Pain , Metabolism , Pain Management , Random Allocation , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Objective To explore the reconstructive methods of benign bone tumor defects in proximal joint. Methods Operative treatment was performed in 11 cases with benign bone tumor defects in proximal joint, a-mong whom 4 cases were treated by curettage,cauterization of wall and bone grafting,3 cases were treated by filling branch through segment fibula transplantation with vascular,2 cases were treated by fibula head transplantation with vascular to reconstruct the glenohumeral joint and rediocarpal joint, and 2 cases were treated by artificial joint re-placement. Results The follow-up ranged from 1.5 to 6 years. All of cases got excellent bone unioned without re-lapse and 2 cases of them developed with little limitation in joint function. Conclusion The importance and recon-structive achievement of fibula transplantation in treating the benign bone tumor defects in proximal joint should be thought fully. The indication of artificial tumor prosthesis replacement should be strictly mastered.
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Objective To observe the effects of cell cycle inhibitor on astrocytic proliferation and scar formation and to study neuronal apoptosis after focal cerebral ischemia in rats.Methods Ischemic model was established by photochemistry method.T_2-weighted MRI was performed on the 3rd, 7th, and 30th day after focal cerebral ischemia.The expression of glial fibrillary acidic protein(GFAP)and apoptosis was observed by immunofluorescence.The protein levels of GFAP and proliferation cell nuclear antigen (PCNA), CyelinA and CyclinB1 were measured by Western blotting from the ischemic and sham animals finished on the 3rd, 7th, and 30th day.Results A marked and significant reduction of brain infarction volume was found in Olomoucine-treated ischemic animals(2.27%?0.28% , 1.87%?0.19%, 1.08%? 0.18%)as compared with controls(5.10%?0.35%, 4.60%?0.26%, 3.96%?0.28%, P