Since Hosobuchi first found that spinal cord stimulation had the effect of significantly increasing cerebral blood flow (CBF) more than two decades ago, spinal cord stimulation had attracted wide attention in the field of treating cerebral ischemia. A large number of animal and clinical studies have been performed in this field, which make it another research focus following thrombolysis and interventional therapy. This article reviews the research history, mechanisms, and current status of clinical applications of spinal cord stimulation in cerebral ischemia protection.

ObjectiveTo investigate and compare the efficacy, safety, and cost effectiveness in the treatment of painful osteoporotic vertebral compression fractures ( OVCFs ) with percutaneous vertebroplasty (PVP) and kyphoplasty(PKP). MethodsSeventy-two patients (96 vertebrae) with painful OVCFs were treated by PVP (n ＝34) or PKP (n ＝38) under radiological monitoring. After bone biopsy needle into the compressed vertebra, bone cement (polymethylmethacrylate) was injected in PVP group, and that was inserted followed by the inflation of vertebra to create cavities in PKP group. The fluoroscopy time, total amount of bone cement injected, and cost were recollected respectively. The score of visual analogue scale point( VAS, 10-point scale)was determined at before the procedures, and 24 hours, one week, and one month after the procedures.Pain relief and complications were observed.The Cobb angle and vertebral heights of the anterior, middle, and posterior border were measured pre-and post-operative. ResultsThe two procedures were technically successful in all patients. The follow-up ranged from 1. 0 to 34. 0 months [mean time, (8. 9 ±3.2) months]. The Mean fluoroscopy time of treating per vertebra in PVP group was ( 11. 1 ± 10. 6 ) min, which was significant shorter than that ( 23.5 ± 13. 0) min in PKP group( P ＜0. 05 ).The mean total cost per patient was (5127. 2 ± 502.3 ) yuan in PVP group, which were strikingly lower than that(32 301.4 ±3204. 6) yuan in PKP group (P ＜0. 05).(3)There was no significant difference( P ＞0. 05 ) in average cement volumes in PVP group [ (4. 9 ± 1.1 ) ml]and PKP group [ (5.4 ± 1.7 ) ml]. Pain relief of was observed in 94. 1％ (32/34) of PVP group and in 92. 1％ (35/38) of PKP group. The score of VAS at pre-operation was (8. 3 ±0. 4 vs 7.9 ±0. 8) ,and at post-operative 24 h (2. 9 ±0. 9 vs 2. 8 ± 1. 2),1 week (2.6 ± 0. 9 vs 2.6 ± 1. 1 ), and 1 month (2.6 ± 0. 9 vs 2. 5 ± 1.3 ) were no difference at PKP and PVP group(P ＜0.05). There was significant difference between pre- and post-operative time point in each group. The Cobb angle, anterior and middle height of vertebra was corrected in both PVP and PKP group. In PVP group, the preoperative Cobb angle, anterior and middle height of vertebra was (24. 2 ± 3.8 )°,( 19. 1 ± 1.4) mm, (25. 2 ± 1.0) mm, which was significant different ( P ＜ 0. 05 ) from that of ( 19.4 ±3.9)°, (21.0 ± 1.5) mm, (27.0 ± 1.2) mm at pre-operation.In PKP group,there was significant difference (P ＜ 0. 05 ) in the preoperative Cobb angle, anterior and middle height of vertebra [(25. 1 ±5.0)°vs(10.7 ±2.8)°, (19.5 ± 1.5) mm vs (24.3 ± 1.9) mm, (25.4 ± 1.1) mm vs (29.7 ±1.3) mm, respectively]. As to the above index, the overall correcting effect in PKP was much better than that in PVP( P ＜0. 05 ). Cement leakage occurred in 9 cases in PVP group and 3 cases in PKP group ( P ＜0. 05 ) but no symptoms. There were no major complications during operation in the two groups. Conclusion PVP and PKP are effective and safe in the treatment of painful OVCFs but PVP is more cost effective than PKP.

OBJECTIVETo investigate the effects of asymmetric dimethylarginine (ADMA) on ACAT-1 expression and cholesterol content in THP-1-derived macrophages and foam cells.

METHODSTHP-1 cells were induced to differentiate into macrophages and further into foam cells. The macrophages and foam cells were exposed to different concentrations (0, 3.75, 7.5, 15, and 30 µmol/L) of ADMA for varying time lengths (6, 12, and 24 h), and the changes in ACAT-1 mRNA and protein levels in the cells were measured with RT-PCR and Western blotting. The cellular cholesterol content was measured with enzyme-linked colorimetry assay.

RESULTSIn THP-1-derived macrophages and foam cells, the expression levels of ACAT-1 mRNA and protein and cellular cholesterol content increased significantly in response to ADMA treatment in a time- and concentration-dependent manner.

CONCLUSIONADMA may play an important role in inducing foam cell formation from macrophages. ACAT-1 inhibition targeting the macrophages and foam cells may serve as a potential therapeutic target in the treatment of atherosclerosis.

Acetyl-CoA C-Acetyltransferase ; metabolism ; Arginine ; analogs & derivatives ; pharmacology ; Cell Line ; Cholesterol ; analysis ; Foam Cells ; cytology ; metabolism ; Humans ; Macrophages ; cytology ; drug effects ; metabolism ; Monocytes ; cytology ; drug effects ; RNA, Messenger ; genetics ; Up-Regulation

Objective　To verify the safety and feasibility of applying transperitoneal laparoendoscopic single-site surgery (LESS) nephrectomy in the treatment of kidney malignant and benign diseases.Methods　From Nov.2010 to Jun.2012,we had used LESS nephrectomy technique treated four kidney tumors,one renal pelvic tumor and one atrophic kidney. Quadport was introduced into abdominal cavity through a paraumbilical incision. Conventional laparoscopic instruments,prebent laparoscopic instruments and flexible tip 5mm laparoscope were used. The standard laparoscopic transperitoneal nephrectomy technique was then performed.We evaluated this technique in respects of operative time,estimated blood loss,intraoperative complications,1st post-operative day pain (VAPS),drainage time,post-operative hospital stay and pathological results.　Results　The 6 procedures in this group were completed successfully with LESS nephrectomy. There was no additional trocar added,no conversion to conventional laparoscopic or open surgery.Application of Quadport and prebent instruments reduced the clash of instruments,both intracorporally and extracorporally.The average operative time were 181.7 (145.0 -235.0) min,average estimated blood loss were 78.3 (20.0 - 150.0) ml.There was no severe intraoperative complication.The average VAPS in the first post - operative day was 1.7 ( 1.0 - 2.0).The average drainage time was 2.8 ( 1.0 -4.0) d,post-operative hospital stays was 6.8 ( 1.0 - 10.0) d.There was no secondary bleeding or wound infection.Pathological results showed 3 cases of renal clear cell carcinoma,1 case of chromophobic carcinoma,1 case of high-grade urothelial carcinoma and 1 case of atrophic kidney.All the specimens in this group were surgical margin negative.　Conclusions　LESS nephrectomy is a safe and feasible treatment option for the treatment of kidney surgical diseases.

The aim of the study is to evaluate the effects of the single and mixed decoction of Thallus laminariae (kelp) and Glycyrrhiza glabra (licorice) on the metabolism and their difference. The mixed decoction of kelp and licorice and the single decoction were made and intragastrically administered to the SD rats. The effect on system metabolism, the toxicity of liver and kidney were assessed by GC-MS profiling of the endogenous molecules in serum, routine biochemical assays and histographic inspection of tissues from SD rats, separately. The mixed decoction of kelp and licorice induced more obvious pathological abnormalities in SD rats than a single decoction of kelp, while the extracts of licorice did not show any pathological change. Neither the mixed, nor the single decoction showed abnormal histopathology. After intragastric administration of extracts for 5 days, the mixed decoction induced a decrease of ALT (no significant change in the groups of single decoction) and an increase of BUN (so did the single decoction of kelp). Metabolomic profile of the molecules in serum revealed that the metabolic patterns were all obviously affected for the three groups, i.e., the mixed and single decoction of kelp and licorice. The rats given with the single decoction of kelp showed a similar pattern to that of the mixed decoction, indicating that the kelp primarily contributed the perturbation of metabolism for the mixed decoction. All three groups induced a decrease of branched chain amino acids, TCA cycle intermediates and glycolysis intermediates (e.g., pyruvic acid and lactic acid) and an increase of 3-hydroxybutyric acid. Kelp decoction showed stronger potential in reducing TCA cycle intermediates and glycolysis intermediates than the other two groups, while the levels of branched chain amino acids were the lowest after licorice extracts were given. These results suggested that the effect of the mixed decoction on metabolism was closely associated with both kelp and licorice. The continuous administration of single decoction of kelp and the mixed decoction of licorice and kelp resulted in pathological abnormalities in kidney of SD rats. The mixed decoction of kelp and licorice distinctly perturbed sera molecules and hence system metabolism, which showed associated with those of kelp and licorice. Although the metabolic effect was associated with both kelp and licorice, the results suggested kelp contributed to it primarily.
Animals ; Glycyrrhiza ; chemistry ; Kelp ; chemistry ; Kidney ; drug effects ; Liver ; drug effects ; Metabolomics ; Plant Preparations ; pharmacology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the immunoregulatory activities of polysaccharopeptide and astragalus polysaccharides on EAC tumor-bearing mice.

METHODEhrlich's ascites carcinoma (EAC) Kunming (KM) mice were used to establish the animal model for solid tumor. Mice were randomly divided into six groups (n = 10): NS group (NS, 10 mL x kg(-1) x d(-1)), AMD group (AMD, 4 mg x kg(-1) x d(-1), 0.2 mL, only for the first 3 days), PSP group (PSP, 250 mg x kg(-1) x d(-1), 0.2 mL), APS group (APS, 250 mg x kg(-1) x d(-1), 0.2 mL), complex prescription group (PSP + APS, 250 mg x kg(-1) x d(-1), 0.1 mL) and combined treat group (AMD + PSP + APS, same dosage as above). After thirty days of treatment, immunocytochemical method was employed to detect the changes of T-lymphocyte subsets in the PBMC of tumor-bearing mice. Subsequently, the organ indexes and tumor inhibition rate were calculated and compared with those of control group.

RESULTPercentage of CD3+, CD4+ T-cell and the ratio of CD4+/CD8+ were obviously prominence in the PSP and PSP + APS groups compared with those of NS group (0.05), percentage of CD8+ T-cell was significantly decreased compared with that of AMD group; percentage of CD3+, CD4+ T-cell were obviously increased in AMD + PSP + APS group relative to that of AMD group; the thymus index of AMD group was significantly decreased compared with that of NS group, but the thymus index of AMD + PSP + APS group was obviously increased compared with that of AMD group; the weight of tumor in each administration group was significantly decreased compared with that of NS group.

CONCLUSIONPSP and PSP + APS complex prescription showed the remarkable immunoregulation on EAC mice with chemotherapy or not.

Animals ; Antineoplastic Combined Chemotherapy Protocols ; Astragalus Plant ; chemistry ; immunology ; Carcinoma, Ehrlich Tumor ; drug therapy ; immunology ; pathology ; Female ; Mice ; Polysaccharides ; administration & dosage ; immunology ; pharmacology ; therapeutic use ; Proteoglycans ; administration & dosage ; immunology ; pharmacology ; therapeutic use ; T-Lymphocyte Subsets ; drug effects ; immunology

OBJECTIVETo investigate the effect of ADMA on macrophage migration inhibitory factor (MIF) expression and tumor necrosis factor-α (TNF-α) and IL-8 secretion in THP-1 monocyte-derived macrophages. METHIDS: THP-1 monocytes were induced to differentiate into macrophages by a 24-h incubation with 160 nmol/L PMA. The THP-1 monocyte-derived macrophages were exposed to different concentrations of ADMA for 24 h, and the changes in MIF mRNA and protein expressions were analyzed with RT-PCR and Western blotting, respectively. Enzyme-linked immunosorbent assay was used to detect the levels of TNF-α and IL-8 in the supernatant of THP-1-derived macrophages following ADMA treatments.

RESULTSADMA obviously up-regulated MIF mRNA and protein expressions in THP-1-derived macrophages in a concentration- dependent manner. Exposure of the cells to 15 µmol/L ADMA for 24 h showed the most potent effect in up-regulating MIF mRNA and protein expressions. ADMA treatment also resulted in a dose-dependent increase of the levels of TNF-α and IL-8 in the culture supernatant of the macrophages, and the peak levels occurred following the treatment with 15 µmol/L ADMA.

CONCLUSIONADMA can up-regulate MIF expression and induce TNF-α and IL-8 secretion in THP-1 monocyte-derived macrophages.

Arginine ; analogs & derivatives ; pharmacology ; Cell Differentiation ; Cell Line ; Humans ; Interleukin-8 ; secretion ; Intramolecular Oxidoreductases ; genetics ; metabolism ; Macrophage Migration-Inhibitory Factors ; genetics ; metabolism ; Macrophages ; cytology ; metabolism ; Monocytes ; cytology ; Phenanthrenes ; pharmacology ; RNA, Messenger ; genetics ; metabolism ; Tumor Necrosis Factor-alpha ; secretion

OBJECTIVETo study the effect of low- and intermediate-dose factor VIII (FVIII) for prophylactic treatment of severe hemophilia A in children by comprehensively evaluating the outcomes of the joints.

METHODSForty-seven children with severe hemophilia A (FVIII activity ≤2%) were enrolled in this study. Eighteen of the children received prophylactic treatment with low-dose FVIII (10 U/kg, 2-3 times a week), 20 received prophylactic treatment with intermediate-dose FVIII (15-30 U/kg, 3 times a week), and 9 received on-demand treatment with FVIII infusion when bleeding occurred according to the Chinese Expert Consensus on the Diagnosis and Treatment of Hemophilia. The children were followed up for 180 days to observe the changes in the indexes of clinical bleeding phenotype, joint structure, joint function, and joint mobility, and the correlation of these indexes were analyzed.

RESULTSCompared with on-demand treatment, prophylactic treatment with low- and intermediate-dose FVIII significantly improved the clinical hemorrhage phenotype (P<0.01), and the improvement was significantly more conspicuous with intermediate-dose prophylactic treatment (P<0.05). Comprehensive evaluation of the joint structure and function changes showed that compared with on-demand treatment, prophylactic treatment with low- and intermediate-dose FVIII resulted in significant improvements in the total score of Hemophilia Joint Health Score (HJHS), Functional Independence Score in Hemophilia (FISH), the single most severe target joint ultrasound and HJHS score of the target joint (P<0.05) and prophylactic treatment with intermediate-dose FVIII appeared to produce better outcomes of the joint than low-dose FVIII. No correlation was found between annual target joint bleeding rate (ATJBR) and ultrasound score, between ATJBR and HJHS change, or between annual joint bleeding rate (AJBR) and the total score of FISH (P>0.05).

CONCLUSIONCompared with on-demand treatment, prophylactic treatment with low- and intermediate-dose FVIII can significantly improve the bleeding phenotype and delay the progression of joint injury, but the clinical hemorrhagic phenotype is not sufficient to monitor the disease progression.

Background Researches showed that elevatory blood glucose level results in long-term damage of cells and tissue,or metabolic memory phenomenon,and manipulation of hyperglycemic memory is a good approach in the prevention of diabetic complications.However,its mechanism is not clear.It is speculated that the pathogenesis of diabetic retinopathy (DR) in diabetic patients may be associated to related mechanisms.Uncoupling proteins (UCPs) can decrease the production of reactive oxygen species (ROS),which may be related to DR.Objective This study was to explore the association between DR and the single nucleotide polymorphisms (SNPs) of UCP genes in Chinese Han population with type 2 diabetes.Methods A cross-sectional study was performed.This study was approved by Ethic Committee of Affiliated First Hospital of Shanghai Jiao Tong University and complied with Declaration of Helsinki,and written informed consent was obtained from each subject prior to any medical examination.One thousand eight hundreds and seventy-five patients with type 2 diabetes mellitus were enrolled in Xinjing district of Shanghai city by cluster sampling from November 2014 to January 2015.The demographic and medical baseline characteristics,ocular examination and laboratory tests were obtained and periphery blood of 2 ml was collected for extraction of DNA.Eight tag SNPs of UCP1,three tag SNPs of UCP2,and seven tag SNPs of UCP3 were selected as marker locus for the detection of genotype by Sequenom Mass ARRAY.Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry platform were used for genotyping.Hardy-Weinberg equilibrium (HWE) analysis,allele and genotype frequencies,haplotype analysis,and association tests for DR and SNPs were performed by SAS and SHEsis software.Results A total of 530 DR patients were checked out from 1 875 subjects with type 2 diabetes mellitus,with the detection rate of 28.27％.rs660339 locn of UCP2 gene and rs1626521,rs668514 locus of UCP3 gene appeared to have low detectable rates,and the secondary allele base frequency of rs632862 in UCP2 gene was ＜0.01 and rs15763 of UCP3 gene was unmatched with HWE,therefore,these locus analysis was not included.In 13 SNPs locus included in the analysis,only 2 SNPs of UCP1 gene were related to DR.Compared with the non-diabetic retinopathy (NDR) patients,the G allele frequency of rs10011540 was increased (P =0.03,OR =1.31,95 ％ confidence interval[CI] =1.03-1.67,and T allele frequency of rs3811787 was decreased (P=0.04,OR=0.86,95％ CI=0.75-0.99) in DR patients.Genotyping detection showed that the C/C and A/A frequencies of rs3811790 in UCP1 gene were significantly more and C/A frequency was less in DR patients than those in NDR patients (all at P＜0.01).The logistic regression analysis indicated an association of SNPs of rs10011540 and rs3811787 with DR independent from glucose and disease duration.Conclusions The SNPs of rs10011540 and rs3811787 locus in UCP1 gene are associated with DR in Chinese type 2 diabetes patients.

Objective:To explore the effects of coenzyme Q10(CoQ10) on high-fat diet-induced obesity, lipid disorders, and bile acid metabolism in mice.Methods:Eight-week-old C57BL/6J mice were randomly divided into control group(regular chow), high-fat diet group(45% high-fat chow), and CoQ10 intervention group(45% high-fat chow+ 100 mg·kg -1·d -1CoQ10) based on their body weights according to the randomized block design. The body weight and food intake of mice in each group were collected. The levels of serum total cholesterol, triglyceride, low density lipoprotein-cholesterol, high density lipoprotein-cholesterol, alanine aminotransferase, and aspartate aminotransferase were detected. The contents of 17 bile acids in serum, liver, and colon contents of mice were detected by ultra-performance liquid chromatography-tandem mass(UPLC-MS/MS). The protein expressions of cholesterol 12α-hydroxylase(CYP8B1) and oxysterol 7α-hydroxylase(CYP7B1) in liver were detected by Western blotting. Results:CoQ10 significantly reduced body weight and ameliorated lipid metabolism disorders in mice fed a high-fat diet. Compared with the control group, serum total bile acid levels were reduced in the high-fat diet group( P<0.05); CoQ10 intervention elevated serum and colonic total bile acid levels( P=0.021, P=0.014) and increased liver, colon, and serum deoxycholic acid and ursodeoxycholic acid levels( P<0.05) in the mice compared with the high-fat diet group. Both colonic and serum deoxycholic acid levels in the CoQ10 intervention group were negatively correlated with body weights( P=0.024, P=0.019), and colonic deoxycholic acid and total cholesterol levels were also negatively correlated( P=0.006). CoQ10 increased the expression of CYP8B1 and CYP7B1 proteins in the liver of mice. Conclusion:CoQ10 can modulate bile acid metabolism in high-fat diet-fed mice and alleviate their obesity and lipid metabolism disorders.