To explore the effect of high glucose on the NF-κB/IκB signal pathway in cultured rat glomerular mesangial cells. The results showed that high glucose increased the degradation of IκB-α and the translocation to nucleus of NF-κB. These changes could be reverted mostly by MG132, a proteasome inhibitor. It suggests that the activation of the NF-κB signal pathway by high glucose concentration may probably be via the ubiquitin-proteasome pathway.

Objective To investigate the effects of ketogenic amino acid ( KAA) replacement diet on insulin resistance in mice fed with high fat diet(HFD) and to analyze the possible mechanism. Methods C57BL mice were fed with a control diet, HFD, and KAA-fortified HFD(HFDKAAR)from the age of 8 weeks, and 8 weeks after HFD initiation, the HFD-fed mice were divided into two groups:one group of mice were fed the same HFD, the other group were fed HFDKAAR ( HFD→HFDKAAR ) . The metabolic evaluations were performed at the end of 16 weeks. Blood glucose levels were measured at 0, 15, 30, 60, 90, and 120 min after the injection of glucose ( 1 g/kg BW intraperitoneal glucose tolerance test, ipGTT) . The insulin,β-hydroxybutyrate, and acetoacetate levels in the plasma were measured via ELISA. The insulin resistance index ( IRI) and area under curve ( AUC) were calculated. The expression of hepatic LKB1 ( liver kinase B1 ) , AMP-activated protein kinase ( AMPK ) , and mTOR ( Mammalian target of rapamycin ) protein, and mcp-1 mRNA were measured by western blot and real-time PCR respectively. Results HFD-fed group of mice displayed significantly heavier body weight,heavier intra-abdominal fat weight, and significant deterioration of glucose tolerance at the end of 16 weeks in addition to higher insulin levels( all P<0. 05), HFDKAAR-fed mice exhibited significantly ameliorated high fat diet-induced obesity and glucose intolerance compared to the HFD-fed mice, which was associated with decreased insulin levels, IRI, AUC, and mcp-1 mRNA expression (all P<0. 05). HFD suppressed hepatic LKB1 and AMPK phosphorylation expression, and increased mTOR phosphorylation levels compared to the control diet-fed mice(all P<0. 05). In contrast, treatment with the HFDKAAR diet increased LKB1and p-AMPK expression, which was associated with suppressed p-mTOR levels compared to the HFD-fed mice(all P<0. 05). Conclusion KAA may ameliorate high fat diet-induced obesity, glucose intolerance, via normalizing the hepatic LKB1-AMPK-mTOR nutritional signal passageway. KAA replacement diet seems to be a potential nutritional intervention for the treatment for patients with metabolic defects, such as obesity, glucose intolerance, as well as metabolic syndrome.

BACKGROUND: Interlocking nail implantation exhibits great stability and preventory effect on fracture shortening or rotation.OBJECTIVE: To evaluate the reasons and countermeasures for the complication after interlocking nail implantation in treating femoral fracture.DESIGN, TIME AND SETTING: The case analysis was performed at Department of Orthopedics, Changhai Hospital of Second Military Medical University of Chinese PLA from April 1987 to April 2008.PARTICIPANTS: 352 patients underwent femoral interlocking nail implantation, including 289 male and 63 female with an average age of 35.9 years (range 18-84 years).METHODS: 127 patients were treated with close interlocking nail implantation, of which 30 cases were subjected to minimal incision to assist nail insertion; 24 were treated with dynamic interlocking nail implantation; 321 with static interlocking nail implantation, and 38 with interlocking nail implantation for femoral reconstruction.MIAN OUTCOME MEASURES: Complications post-implantation; limb joint function recovery during long-term follow-up.RESULTS: 331 cases were followed-up for over 60 months, and the longest follow-up lasted for 252 months. Complications were found in 16 cases, including deformity union in 2, femoral neck fracture in 1, exit of the nail in 2, infection in 2, breakage in 8 (nonunion in 3), and perineal nerve injury in 1. Except 2 with deformity union and recovered by secondary surgery, all patients developed bone union. During the followed-up, no pain or knocked pain was found with normal pseudoarthrosis activities and functional activities. The excellent function recovery in joints and limbs was 91.2%.CONCLUSION: Nail breakage is the main complication after interlocking nail implantation. Therefore, we should select longer and thicker interlocking nail as the first choice. In addition, the interlocked screws should be distal to fracture site. For the patients with severe trauma, the interlocking nail implantation in early stage of fracture would not increase complications.

BACKGROUND: With the advanced progress of prostheses manufacture and surgical technique, early loosening of hip articulation prostheses and femoral neck fracture tend to reduce after hip surface arthroplasty. Meanwhile hip articulation activity has been improved.OBJECTIVE: To discuss the biocompatibility between the implants and the hosts in patients underwent hip surface arthroplasty and observe the functional recovery of hip articulations.DESIGN, TIME AND SETTING: Retrospective case analysis was carded out in the Department of Orthopaedics, Changhai Hospital Affiliated to the Second Military Medical University of Chinese PLA (Shanghai, China) from January 2006 to August 2007.PARTICIPANTS: Fifty-two patients with hip articulation diseases, including 25 females and 27 males, underwent sixty-three hip surface arthroplasties, and eleven cases of them were subjected to bilateral arthroplasty. Their average age was 47.6 years.METHODS: Hip resurfacing prostheses were offered by Zimmerm Company (Huntington, Indiana, USA). Hip resurfacing was performed using 4-mm-thick cement-less acetabular bone (metal acetabular cup of 3.7-ram thickness was coated with 0.3-mm plasma titanium). Acetabular cup exhibits large diameter and arch shape (165°), is coated with 0.3-ram plasma titanium and fixed with cement less. By means of posterolateral approach, acetabular prostheses were implanted to the central position of hip articulation with regards to anatomy. Acetabular prostheses were covered more than 90% area.MAIN OUTCOME MEASURES: Subsequent to the arthroplasty, biocompatibility between the implant materials and the hosts was recorded, such as dislocation and infection. Functional recovery of the patients was assessed with Harris hip score at 1, 3, 6 and 12 months after operation and annually thereafter. Radiological evaluation was conducted to record radioactive permeability in the areas of 1 ram around acetabular cup in the DeLee and Charnley zone.RESULTS: All patients were involved in the follow-up. There were no cases of dislocation, deep venous embolism, deep infection or neurovascular complications that required further treatment. The mean Harris score was 38 points before operation and significantly increased to 90 points after operation. Two patients appeared a 2-mm crevice below acetabular prostheses, which disappeared 6 months after arthroplasty. Acetabular or femoral prostheses removal, or local osteolysis was detectable.CONCLUSION: Metal-on-metal hip surface arthroplasty has excellent early effects on young and active patients. The arthroplasty potentially offers the ultimate bone preservation and better restoration of hip articulation function in patients, without specific biocompatibility.

Objective To evaluate retrospectively the role of 18 F-fluorodeoxyglucose (FDG) PET/CT associated with MRI in the localization of epileptogenic foci. Methods Sixty-seven patients with medically resistant epilepsy were included from 2003 to 2008. All underwent 18F-FDG PET/CT and MRI for presurgical evaluation as well as post-surgical evaluation 12 to 65 months after operation. Based on postoperative seizure occurrence, patients were divided into two groups. One group was free of seizures ( Engel classification Ⅰ, Group 1) and the other was with postoperative seizure occurrence of any type ( Engel classification Ⅱ-Ⅳ, Group 2). X2-test or Fisher's exact test was used for the statistical analysis. Results About 71.6% (48/67) patients were defined as group 1, and 19 patients were group 2 ( 11 were Engel Ⅱ , 5 were Engel Ⅲ, and 3 were Engel Ⅳ ). In Group 1, no statistically significant difference was found between concordant (45/63) and discordant findings (3/4) with regard to 18F-FDG PET/CT and MRI images (Fisher's exact test, P ＞0.05). For 41 patients that showed focal abnormality both on MRI and 18F-FDG PET/CT, 80.5% (33/41) were found in group 1. For 20 patients that showed focal lesions on MRI while with multi-focal or generalized abnormal metabolism on 18F-FDG PET/CT, 11 (55.0%) were in group 1 and9 (45.0%) were group 2. There was no significant difference (33/41 vs 11/20, X2 =4.34, P ＜0.05 ). Conclusion 18F-FDG PET/CT associated with MRI may offer more helpful information for pre-surgical evaluation and prediction of prognosis of epileptic patients.

Objective To explore the relationship between corticospinal tract (CST) repairment and motor function recovery after rehabilitation in stroke patients by diffusion tensor imaging (DTI). Methods 15 stroke patients with internal capsule lesions and injured CST, 4-8 weeks after onset were included. They were scanned with DTI and assessed with the simple Fugl-Meyer Assessment (FMA) before and after 3-month rehabilitation. The fractional anisotropy (FA), FA ratio (rFA) and FA asymmetry (FAasy) in cerebral peduncle, posterior limb of internal capsule (PLIC) and corona radiate were obtained. The correlation of differences of FA, rFA and FAasy of CST with FMA was analyzed. Results The scores of FMA increased after treatment (P<0.01). The FA of the ipsilesional CST were significantly less than that of contralesional ones before and after rehabilitation. There was statistical differences in FA, rFA and FAasy in the corona radiate section of CST after treatment (P<0.05), but was not in the cerebral peduncle and PLIC section. However, there was no significant correlation of FA, rFA and FAasy of corona radiate section to scores of FMA. Conclusion DTI can respond to the repairment of corticospinal tract after stroke, especially in the corona radiate section.

Objective To explore brain plasticity of upper extremities motor function recovery after stroke with diffusion tensor imaging (DTI). Methods 25 stroke patients with internal capsule lesions and affected corticospinal tract (CST), 4-8 weeks after onset, were divided randomly into rehabilitation group (n=13) and control group (n=12). Both groups received routine medication and the rehabilitation group also received rehabilitation. All the patients were scanned with DTI and assessed with upper extremity Fugl-Myer Assessment (UE-FMA) before and 3 months after treatment. The fractional anisotropy (FA), FA ratio (rFA) and FA asymmetry (FAasy) in cerebral peduncle, posterior limb of internal capsule (PLIC) and corona radiate were obtained. The bilateral corticospinal tracts were reconstructed with diffusion tensor tractography. Results The scores of UE-FMA increased in both groups after treatment (P<0.05), and increased more in the rehabilitation group than in the control group (P<0.05). There was significant difference in FA, rFA and FAasy in the corona radiate section of CST after treatment in the rehabilitation group (P<0.05), but was not in the cerebral peduncle and PLIC section. However, there was no significant differences in FA, rFA and FAasy in the control group. The ipsilesional CST fibers were more compact after treatment in the rehabilitation group. Conclusion Rehabilitation can improve the upper extremities function recovery after stroke, which may associated with the repairment of CST in the corona radiate section.

Objective To construct cDNA entry library and cDNA expression library of Armillifer agkistrodontis (A.) nymphs and make a preliminary immunoscreening for the cDNA expression library.Methods The nymphs were collected from the Kunming mice infected experimentally with A.agkistrodontis eggs and the total RNA were extracted from the nymphs using TRIzol Reagent.After purifying the mRNA,the synthesized cDNAs were cloned into the donor vector pDONR222 by BP reaction of Gateway technology and the recombinants were transformed into the DH10B cells by electroporation,the cDNA entry library was obtained.Next,the expression vector pDEST17 was ligated with entry clones by LR reaction,and the recombinants were transformed into the BL21 (DE3) cells.Hence,the cDNA expression library was constructed.Then,the expression library was immunoscreened with the mixed sera of mice infected with A.agkistrodontis,and the insertions of positive clones were sequenced.After that,the open reading frame(ORF) of positive slone sequence,the homology of the screened genes and their encoded proteins were analyzed by Finder and BLAST (basic local alignment search tool) program of National Center of Biotechnology Information(NCBI),and the discovered new genes were submitted into the GenBank.Besides,the physico-chemical properties,secondary structure and B cell epitopes of encoded proteins were also analyzed by bioinformatics software.Results The average titer and total clones of the cDNA entry library were 1.45 × 105 CFU/ml(colony-forming unit,CFU) and 1.74 × 106 CFU,respectively,and the range of fragment length of the inserted cDNA was between 0.2-4.0 kb,with an average of 1.4 kb.The total clones of cDNA expression library were 1.00 × 105 CFU,and the fragment length of the inserted cDNA was between 0.3-2.2 kb,with an average of 1.0 kb.Five positive clones,coded S1,S5,A1,D1 and F1,respectively,were obtained through preliminary immunoscreening.The sequence and homology of the five positive clones were sequenced and analyzed by BLAST program.No significant similarities were found in pentastomida species,which meant that they were all novel genes of A.agkistrodontis.The gene sequences were submitted to GenBank,with the accession number from JQ180451 to JQ180455.Also,results obtained by bioinformatics software showed that the predictive encoding proteins were all potential to be valuable recombinant diagnostic antigens.Conclusions The cDNA library of A.agkistrodontis nymphs is successfully constructed,and five new genes of A.agkistrodontis are discovered.The establishment of cDNA library and the discovery of the new genes will lay a foundation for further studying the gene functions and screening the immunodiagnostic antigens.

The study on the effective core formulae (CEF) not only summarized traditional chinese medicine (TCM) treatment experience, but also helped reveal the underlying knowledge in the formulation of TCM prescriptions. The aim of the present paper was to investigate the method of data mining for the discovery of core effective formulae for lung cancer. In the present study, a prescription fingerprint approach was used to characterize the staged prescription information of patients. The D index was used to screen potential beneficial herbs. Then, based on a herbal compatibility network, the maximal clique searching algorithm (BK algorithm) and survival analysis were applied to discover CEF for lung cancer, and a mining analysis was made for the 322 cases from Longhua hospital. The correlation between prescriptions and survival time was analyzed by prescription fingerprints. Forty-three potentially beneficial herbs were obtained, and two CEFs were significant for the survival time by a parametric survival model based on lognormal distribution, the results were verified by a multivariate survival model. The rules of combination of the two CEFs basically conform to TCM onco-therapeutic theory of strengthening the body resistance and the actual conditions in clinic. All results showed that the established approach was feasible for discovering the core effective formulae for lung cancer and mining survival data for complex TCM onco-therapy.
Algorithms ; Data Mining ; Drug Prescriptions ; Drugs, Chinese Herbal ; chemistry ; therapeutic use ; Humans ; Lung Neoplasms ; drug therapy ; mortality ; Survival Analysis

Prolyl-4-hydroxylase domain (PHDs) family is one of the most important regulatory factors in hypoxic stress. PHD2 plays a critical role in cells and tissues adaptation to the low oxygen environment. Its hydroxylation activity regulates the stability and transcriptional activity of the hypoxia-inducible factor 1 (HIF-1), which is the key factor in response to hypoxic stress. Subsequently, PHD2 acts as an important factor in oxygen homeostasis. Studies have shown that PHD2, through its regulation on HIF-1, plays an important role in the post-ischemic neovascularization. Furthermore, under hypoxic condition, PHD2 also regulates other pathways that positively regulate angiogenesis factors HIF-1 independently. Moreover, recently, several evidences have also shown that PHD2 also affects tumor growth and metastasis in a tumor microenvironment. Based on these facts, PHD2 have been considered as a potential therapeutic target both in treating ischemic diseases and tumors. Here, we review the molecular regulation mechanism of PHD2 and its physiological and pathological functions. We focus on the role of PHD2 in both therapeutic angiogenesis for ischemic disease and tumor angiogenesis, and the current progress in utilizing PHD2 as a therapeutic target.
Animals ; Humans ; Hydroxylation ; Hypoxia-Inducible Factor 1 ; metabolism ; Hypoxia-Inducible Factor-Proline Dioxygenases ; antagonists & inhibitors ; physiology ; Neoplasms ; blood supply ; metabolism ; pathology ; therapy ; Neovascularization, Pathologic ; metabolism ; pathology ; Tumor Microenvironment ; Vascular Diseases ; pathology ; therapy