OBJECTIVE Amyotrophic lateral sclerosis(ALS)is a fetal neurodegenerative disease characterized by the progressive loss of upper and lower motor neu-rons,leading to skeletal muscle atrophy,weakness,and paralysis.Oxidative stress plays a crucial role in ALS pathogenesis,including the familial forms of the disease arising from mutations in the gene coding for superox-ide dismutase(SOD1).Additionally,the abnormal accu-mulation of TAR DNA-binding protein of 43 ku(TDP-43)is a pathological feature present in almost all patients,even though the pathogenesis of ALS is unclear.Current-ly,there is no drug that can cure ALS/FTLD.Tetramethyl-pyrazine nitrone(TBN)is a derivative of tetramethylapyr-azine,derived from traditional Chinese medicine Ligusti-cum chuanxiong,which has been extensively proven to have therapeutic effects on various models of neurode-generative diseases.METHODS We investigated the therapeutic effect of TBN in the SOD1G93A and TDP-43M337V ALS mouse models.In the SOD1G93A trans-genic mouse model,TBN was administered to mice via intraperitoneal or intragastric injection after the onset of motor deficits.We injected the TDP-43M337V virus into the striatum of mice unilaterally and bilaterally,and then administered TBN 30 mg·kg-1 intragastrically to observe changes in behavior and survival rate of mice.RESULTS TBN slowed the progression of motor neuron disease,as evidenced by improved motor performance,reduced spi-nal motor neuron loss and associated glial response,and decreased skeletal muscle fiber denervation and fibrosis.TBN treatment activated mitochondrial antioxidant activity through the PGC-1α/Nrf2/HO-1 pathway and decreased the expression of human SOD1.In the mice with unilateral injection of TDP-43M337V into the striatum,TBN improved motor deficits and cognitive impairment in the early stages of disease progression.In mice with bilateral injection of TDP-43M337V into the striatum,TBN not only improved motor function but also prolonged survival.Moreover,we demonstrate that its therapeutic effect may be through activation of the Akt/mTOR/GSK-3β and AMPK/PGC-1α/Nrf2 signaling pathways.CONCLUSION TBN shows promise as an agent for the treatment of ALS/FTLD.TBN is currently undergoing clinical investigation for several indications,including a Phase Ⅱ trial for ALS.

Memantine is a non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist clinically approved for moderate-to-severe Alzheimer's disease (AD) to improve cognitive functions. There is no report about the proteomic alterations induced by memantine in AD mouse model yet. In this study, we investigated the protein profiles in the hippocampus and the cerebral cortex of AD-related transgenic mouse model (3×Tg-AD) treated with memantine. Mice (8-month) were treated with memantine (5 mg/kg/bid) for 4 months followed by behavioral and molecular evaluation. Using step-down passive avoidance (SDA) test, novel object recognition (NOR) test and Morris water maze (MWM) test, it was observed that memantine significantly improved learning and memory retention in 3xTg-AD mice. By using quantitative proteomic analysis, 3301 and 3140 proteins in the hippocampus and the cerebral cortex respectively were identified to be associated with AD abnormalities. In the hippocampus, memantine significantly altered the expression levels of 233 proteins, among which PCNT, ATAXIN2, TNIK, and NOL3 were up-regulated, and FLNA, MARK 2 and BRAF were down-regulated. In the cerebral cortex, memantine significantly altered the expression levels of 342 proteins, among which PCNT, PMPCB, CRK, and MBP were up-regulated, and DNM2, BRAF, TAGLN 2 and FRY1 were down-regulated. Further analysis with bioinformatics showed that memantine modulated biological pathways associated with cytoskeleton and ErbB signaling in the hippocampus, and modulated biological pathways associated with axon guidance, ribosome, cytoskeleton, calcium and MAPK signaling in the cerebral cortex. Our data indicate that memantine induces higher levels of proteomic alterations in the cerebral cortex than in the hippocampus, suggesting memantine affects various brain regions in different manners. Our study provides a novel view on the complexity of protein responses induced by memantine in the brain of AD.
Alzheimer Disease ; Animals ; Axons ; Brain ; Calcium ; Cerebral Cortex ; Cognition ; Computational Biology ; Cytoskeleton ; Hippocampus ; Learning ; Memantine ; Memory ; Mice ; Mice, Transgenic ; N-Methylaspartate ; Proteome ; Ribosomes ; Water

OBJECTIVE:To establish the fingerprint of Artemisia apiacea to identify common model and evaluate the quality coherence of the commercially available A. apiacea decoration pieces in Chongqing. METHODS:HPLC method was performed on the column of Waters XTerra C18 with the mobile phase consisted of methanol-0.1% phosphoric acid(gradient elution)at the flow rate of 1.0 ml/min. The detection wavelength was 220 nm,column temperature was 30 ℃ and the sample size was 10 μl. The simi-larity of 12 batches of samples was evaluated by TCM Chromatogram Fingerprint Similarity Evaluation System(2004A edition);a common model of fingerprints was identified by principal component analysis(PCA)and cluster analysis(CA). RESULTS:Total-ly 11 batches of samples were screened to establish common model of fingerprints and 16 common peaks were obtained,among which,3 common components were identified;RSDs of precision,stability and reproducibility tests were lower than 2.53%. The similarity of 11 batches of A. apiacea and reference chromatogram was more than 0.990. CONCLUSIONS:The method is stable and easy,and can provide reference for the scientific quality evaluation and control of A. apiacea;the quality of commercially available A. apiacea decoration pieces is generally good,however,there is still a little number of batches with poor quality. The production procedures and supervision of A. apiacea decoration pieces should be strengthened.

Artemisinin is the antidote to malaria, and has made hundreds of millions patients get rid of the disease since application in clinic. At present, the main accesses to artemisinin are directly extracted from Artemisia annua,chemical synthesis and biosynthesis. By comparing the differences of artemisinin production process between China and abroad, this research analyzes the reasons of the problem, and put forward their views and suggestions, so as to provide references for Artemisia annua further research.

Objective To study the prevention and cure effect of immunoregulation therapy on postoperative infectious complications of calculous obstructive jaundice.Methods Prospective,randomized,blind and controlled clinical analysis of 40 patients conforming to the standard of calculous obstructive jaundice was carried out.The patients were divided into two groups at random.One was control group (n=20) with regular therapy,and the treatment group (n=20) with ulinastatin plus thymosin-α1 on the base of regular therapy for 1 week.The immunological indexes were determined before and after therapy on the 1st,3rd,5th、7th and 14th day,including the changes in lymphocyte count,CD14+ monocytes human leukocyte antigen (locus) DR (HLA-DR),and the incidence of postoperative infection were observed.Results The incidence of postoperative infectious complications in treatment group (10％) was remarkable lower than that in control group (30％,P＜0.01).There was significant difference between two groups (P＜0.05).After the 3rd,up to 14th day of therapy,the counts of lymphocyte and CD14+ monocytes HLA-DR were significantly higher than those in control group (all P＜0.05).Conclusions Immunoregulation therapy can improve the prognosis of obstructive jaundice patients in a period of 14 days of observation,and lymphocyte counts and CD14+monocytes HLA-DR were increased significantly,showing that immuno suppression can be ameliorated.Immunoregulation therapy could effectively prevent infectious complications of calculous obstructive jaundice.

Objective To investigate the effect of herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GGV)system driven by human alpha fetoprotein(AFP)enhancer on hepatocellular carcinoma(HCC)cells in vitro and in vivo.Methods HCC-specific eukarotypic expression vector carrying suicide gene driven by AFP enhancer(pAFP-cDNA3.1-TK)was constructed.The plasmid was trasfected to AFP-positive HepG2 cells and AFP-negative SMMC7721 cells by liposomes.Protein and mRNA expressions of TK were detected by RT-PCR or Western blot.The survival rates of HCC cells were detected by methyl thiazolyl tetrazolium assay.The effects of GGV on the in vitro proliferation,survival and apoptosis of HCC cells were observed,and the inhibitive effect of GGV on the survival of HCC cells in vivo was also detected.All data were analyzed by using the t test.Results The pAFP-cDNA3.1-TK was successfully constructed and transfected to the HCC cells.The protein and mRNA expressions of TK were detected in AFP-positive HepG2 cells.GGV dose-and time-dependently inhibited the growth and induced the apoptosis of HepG2 cells in vitro,but it had no effect on SMMC7721 cells.No protein or mRNA expression of TK was detected in the SMMC7721 cells.There was a significant difference on the inhibitory effects of GGV on HepG2 cells and SMMC7721 cells(t =2.58,2.73,3.12,P ＜0.05).GGV specifically inhibited the growth of AFP-positive HepG2 cells,and the inhibition rate was 46%;the growth of AFP-negative SMMC7721 cells was not influenced by GGV.There was a significant difference in the inhibitive effect of GGV on the growth of HepG2 cells and SMMC7721 cells(t = 3.36,P ＜ 0.05).Conclusion HSV-TK/GGV systemdriven by human APF enhancer kills APF-positive HCC cells and inhibits the growth of HCC cells.

Objective To evaluate the surgical treatment for renal cell carcinoma with inferior vena cava tumor thrombus and the clinical significance of multidisciplinary treatment. Methods Two cases of renal cell carcinoma with inferior vena cava thrombus diagnosed by Doppler ultrasonography and CT were included in this retrospective analysis. The tumor thrombus was in level Ⅱ in one case and in level Ⅳ in the other. Coagulation test and complete blood count were done again before surgery. Human albumin, fibrinogen, prothrombin complex, plasma, platelet, UW and irrigating solution were prepared before the operation.Under general anesthesia, surgery was performed using abdomen inverted Y shaped incision. Right radical nephrectomy was finished by the urological surgeon; the vena cava was completely dissected from the renal vein level to the secondary porta of the liver by the hepatobiliary surgeon, the vena cava and the surrounding branch vein were blocked in the upper and lower vena cava tumor thrombus; tumor thrombus was removed completely by the vascular surgeon. In one case (patient with level Ⅳ thrombus ) where the tumour thrombus invaded the wall of the vena cava, the thrombus was found to be extending to the cavo-atrial junction but not into the right atrium. The left femoral venous-right atrial bypass was established, the cardiopulmonary bypass lasted for 241 mia, and the aorta was blocked for 18 min. Salvage autotransfusion was used during surgery, and the hepatic vein of the secondary liver porta was anastomosed to artificial vascular graft.The data for surgical indication, operation time, operative blood loss and postoperative hospital stay were analyzed. Results Right radical nephrectomy and inferior vena cava thrombectomy were performed successfully, and the two patients were discharged on the 15th and 27th day after surgery, respectively. The two patients were followed up for 1 and 16 months after surgery, respectively, and both survived without local recurrence and distant metastasis. Conclusion Radical nephrectomy and inferior vena cava thrombectomy is the preferred method for patients without metastasis, and multidisciplinary cooperation could shorten the operation time, reduce the tumor recurrence and increase the survival rate of patients.

Objective To observe the effects of thymosin alpha-1 on T cell subsets and gastricintestinal reac-tion of patients with gastricintestinal tumor. Methods Twenty patients with gastricintestinal tumor were divided into two groups, observe group(n = 10) received thymosin alpha-1 during chemotherapy, and control group(n = 10) only received chemotherapy, T cell subsets and gastricintestinal reaction were observed. Results Before chemotherapy, CD+4,CD+8 and CD+4/CD+8 of observe group were(43.7±7.5),(27.3±2.8) and (1.5±0.1), and control group were (39.4±6.3), (30.9±2.5) and (1.2±0.6). There was significant difference between them (P < 0.05). After chemotherapy, CD+4, CD+8 and NK cell were (40.6±6.8)、( 29.7±2.6) and (19.1±2.7), control group (35.9±5.7), (33.4±2.4) and (18.6±2.3). There was significant difference between them (P < 0.05). Effec-tive ratio of nausea and vomit of observe group were 72.5% and 60.0%, control group 40.0% and 33.3%, There were significant differences between them(P <0.05). Conclusion Thymosin alpha-1 may ameliorate the function of T cell subsets and gastricintestinal reaction of patients with gastricintestinal tumor.

Objective To investigate the diagnosis and operation treatment of primary intrahepatic cholangiocelhlar carcinoma (PICC), for improving the level of diagnosis and treament of PICC. Methods The clinical data of 18 cases with PICC confirmed by operation were analyzed retrospectively. Results In the early stage, no specific symptoms was found in all the 18 cases, the positive cases of AFP, CEA, CA199 and live cirrhosis were 2, 4, 3 and 4. The diagnostic rates of ultrasound examination, CT and MRI were 11.1%(2/18), 42.9%(6/14) and 45.5% (5/11 ). Seven cases were diagnosed as suffering from PICC and the others were misdiagnosed. Of all the 18 patients, 8 cases underwent radical resection and 10 cases received palliative excision. Conclusions PICC patients lack clinical features and serum tumor marker,the rato of misdiagnosis is high, but that of radical resection is low. Knowing its clinicopathological features well. Radicalresection is the best way for treatment of PICC.

We have brought forward a wavelet-based algorithm for electroencephalograph (EEG) signals--using scale dependent threshold based on median. In comparison with the universal threshold and Sure threshold, our proposed threshold, which is adaptive to the subband noise signals, preserves the noise free reconstruction property and takes lower risk than does the universal threshold; and our proposed threshold overcomes the drawback of Sure threshold. Evidently, the scale dependent threshold based on median is computationally simple and can obtain higher singal-to-noise ratio (SNR) it outperforms the universal threshold and Sure threshlold.
Algorithms ; Artifacts ; Electroencephalography ; Humans ; Signal Processing, Computer-Assisted