Characteristics of vertical drop jump to screen the anterior cruciate ligament injury.

OBJECTIVE: To clarify the characteristics of vertical drop jump (VDJ) for screening athletes at high risk of ACL injury by comparing the kinematic, kinetic and electromyographic variables of different VDJ. SUBJECTS AND METHODS: Thirty male soccer players were recruited to measure parameters of knee kinematics, kinetics, and surface electromyograph during VDJ in four kinds of movements measured (the distance between the take-off feet is 5 cm or 30 cm, and the distance between the landing feet is 5 cm or 30 cm) using the Vicon motion capture system, Kistler3-D dynamometer, and Noraxon surface electromyograph test system. RESULTS: The peak knee abduction moment was significantly greater for landing feet distance of 30 cm compared to landing feet distance of 5 cm, regardless of whether the distance between take-off feet was 5 cm (0.58 vs. 0.44) or 30 cm (0.61 vs. 0.40); regardless of whether the distance between landing feet was 5 cm (22.78 vs. 20.45) or 30 cm (24.32 vs. 21.87), the peak vertical Ground Reaction Force was significantly increased for the take-off feet distance was 5 cm compared to take-off feet of 30 cm. CONCLUSIONS: In the test of VDJ, athletes will adopt different landing strategies for different movement instructions, and the VDJ with the distance of 5 cm between the take-off feet and the distance of 30 cm between the landing feet may be the better maneuver to screen for risk of ACL injury.

The neuroprotective effects of Galectin-1 on Parkinson's Disease via regulation of Nrf2 expression.

OBJECTIVE: Parkinson's disease (PD) is one of the neurodegenerative diseases. Galectin-1 (Gal-1) is expressed in the central nervous system. Our study sought to explore the neuroprotective effect of Gal-1 in 1­methyl­4­phenyl pyridine ion (MPP+)-induced cytotoxicity on SH-SY5Y cells. MATERIALS AND METHODS: SH-SY5Y cells were cultured in vitro, pretreated with Gal-1, and then exposed to MPP+. Thereafter, the generation of reactive oxygen species (ROS) in SH-SY5Y cells was investigated. The effects of Gal-1 on DNA breakage, cell damage (release of lactate dehydrogenase (LDH)), viability, and apoptosis in SH-SY5Y cells were examined by comet assay, LDH assay, WST-1 assay, and flow cytometry, respectively. Additionally, the regulatory effect of Gal-1 on Nrf2 expression was examined by western blot. Zebrafish embryos were pretreated with Gal-1 and then exposed to MPP+. The locomotor ability of zebrafish larvae was then investigated. RESULTS: MPP+ induced the production of ROS in cells, which can be alleviated by pretreatment with Gal-1. Gal-1 protected cells from MPP+-induced cytotoxicity by preventing DNA breakage and cell injury. Gal-1 inhibited apoptosis in SH-SY5Y cells. The neuroprotective effect of Gal-1 could be abolished when Nrf2 expression knockdown. Moreover, exposure to MPP+ decreased the locomotor activity of zebrafish, which was attenuated by pretreatment with Gal-1. CONCLUSIONS: Our study demonstrated that the administration of Gal-1 could protect neurons from cellular stress by preventing apoptosis and eliminating ROS. Moreover, the neuroprotective effect of Gal-1 in neuronal cells could be related to the activation of Nrf2 expression. Therefore, Gal-1 could be a promising strategy for treating PD.

Single nucleotide polymorphisms rs102313, rs118231 and rs201832 of CTEP TaqIB gene correlated with lipid metabolism abnormalities and cerebral infarction in patients with atherosclerosis.

OBJECTIVE: The purpose of this study was to investigate the correlations of cholesterol ester transfer protein (CTEP) TaqIB gene polymorphism with lipid metabolism abnormalities and cerebral infarction (CI) in patients with atherosclerosis (AS). PATIENTS AND METHODS: A case-control study was conducted on 100 AS patients complicated with (CI) as AS+CI group, and 200 AS patients with matched age, gender and race as controls (AS group). Single nucleotide polymorphisms (SNPs) rs102313, rs118231 and rs201832 in the promoter region of CTEP TaqIB gene were classified by conformational differential gel electrophoresis. Then, Chi-square test was carried out to determine whether the distribution frequency of CTEP TaqIB genotypes conforms to the law of genetic equilibrium. In the meantime, the correlations of gene polymorphisms and allelotypes in the promoter region of CTEP TaqIB with CI and lipid metabolism abnormalities in AS patients were analyzed. RESULTS: Hardy-Weinberg genetic equilibrium analysis showed that the three polymorphisms of CTEP TaqIB gene were in accordance with the genetic equilibrium distribution (p>0.05). Moreover, the results of gene association analysis revealed that the polymorphisms rs102313 and rs118231 and allelotypes in the promoter region of CTEP TaqIB gene were correlated with CI in AS patients (p<0.05). Specifically, AS patients with GG genotype and allele G at rs102313 and those with TT genotype and allele T at rs118231 had a higher risk of CI (p<0.05). Besides, the polymorphism rs102313 in the promoter region of CTEP TaqIB gene was markedly related to lipid metabolism abnormalities in AS patients (p<0.05). CONCLUSIONS: The polymorphisms rs102313 and rs118231 in the promoter region of CTEP TaqIB gene are associated with CI in AS patients, and the polymorphism rs102313 is remarkably correlated with lipid metabolism abnormalities in AS patients.

Effects of Secreted frizzled-related protein 1 on inhibiting cardiac remodeling.

OBJECTIVE: To investigate the effect of Secreted frizzled-related protein 1 (Sfrp1) on myocardial fibroblasts through Wnt/ß-catenin signaling pathway. MATERIALS AND METHODS: Rat myocardial fibroblasts were cultured and divided into control group, proliferation group (TGF-ß1 group), and Sfrp1 transfection group (TGF-ß1 + Ad-Sfrp1 group). The control group received no treatment. The TGF-ß1 group was stimulated with TGF-ß1 10 ng/mL for 12 h to establish a proliferation model. The TGF-ß1 + Ad-Sfrp1 group was first transfected with Ad-Sfrp1 virus. On day 3, TGF-ß1 was added at 10 ng/mL to stimulate 12 h. The ß-catenin and the marker protein α-SMA of myofibroblast (MyoFB) differentiation were detected by Western blotting method. In addition, we used MTT to test cell proliferation and flow cytometry to test cell cycle. At the same time, we used enzyme-linked immunosorbent assay (ELISA) to detect the collagen I and collagen III content of the cell supernatant and used quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) to test the expression of apoptotic factors and Dvl-1 and Cyclin D1. RESULTS: In TGF-ß1 group, the ß-catenin, and α-SMA protein expressions were all upregulated, the OD value and collagen I and collagen III contents were increased, but the apoptosis rate was decreased. On the contrary, the expression of ß-catenin and α-SMA proteins in the TGFß1 + Ad-Sfrp1 group were all downregulated, the OD value, collagen I and collagen III content, and percentage of S-phase cells were reduced, but the percentage of G0/G1, G2/M-phase cells, and the apoptotic rate increased. CONCLUSIONS: Sfrp1 can effectively inhibit myocardial fibroblast proliferation, collagen synthesis, promote fibroblast apoptosis, and inhibit the transformation of fibroblasts into myofibroblasts by inhibiting Wnt/ß-catenin signaling pathway.

CCL3 participates in the development of rheumatoid arthritis by activating AKT.

OBJECTIVE: To investigate whether CC chemokine 3 (CCL3) could exert a certain effect on rheumatoid arthritis (RA) by regulating inflammatory responses and provide a new direction for the treatment of RA. PATIENTS AND METHODS: Totally 47 RA patients (10 males and 37 females) with complete clinical data were included. Meanwhile, 27 healthy volunteers with same age and gender were recruited as healthy controls. The mRNA and protein level of CCL3 in the peripheral blood mononuclear cells (PBMCs) of RA patients and normal controls were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot, respectively. The inflammatory infiltration of synovial tissue was observed by hematoxylin and eosin (HE) staining. Immune fluorescence was used to further analyze the level of CCL3 in T and B cells of synovial tissue in RA patients. Simultaneously, real-time flow cytometry was applied to detect the level of CCL3 in T and B cells of PBMCs in the normal control group and the RA group. Western blot was used to detect the level of pAKT in RA-FLS treated with different concentrations of recombinant human CCL3. Besides, enzyme-linked immunosorbent assay (ELISA) was applied to detect the levels of interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α) and receptor activator of nuclear factor kappa-B ligand (RANKL) in the culture supernatant of RA-FLS stimulated by different doses of recombinant human CCL3. RESULTS: The level of CCL3 in peripheral blood and synovial fluid of RA patients was markedly higher than that of normal controls. Inflammatory cells were infiltrated in synovial tissue of RA patients. Meanwhile, CCL3 was mainly expressed in CD4+ T cells. CCL3 treatment in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) could activate the PI3K/AKT signaling pathway to different degrees and increase the expression of cytokines including interleukin-6 (IL-6), IL-1ß, TNF-α, and RANKL. These results indicated that CCL3 might participate in the progression of RA by activating AKT. CONCLUSIONS: We showed that CCL3 enhanced the expression level of pro-inflammatory cytokines such as IL-6, IL-1ß, TNF-α, and RANKL by activating the PI3K/AKT signaling pathway. Besides, CCL3 could up-regulate CD4+T cells to mediate the inflammatory response of RA. These findings might provide new directions for the prevention of RA.

Sorafenib in combination with transarterial chemoembolization for hepatocellular carcinoma: a meta-analysis.

OBJECTIVE: This meta-analysis aimed to analyze the efficacy of sorafenib in combination with transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Electronic data bases were searched for studies (1) enrolled HCC patients undergoing TACE; (2) with sorafenib therapy and control arm of no sorafenib therapy were included for meta-analysis and meta-regression; (3) studies without control arm were included for data review and (4) had time to progression (TTP) and overall survival (OS) or relative outcome of HCC as the endpoint. Meta-analysis and meta-regression were performed according to Cochrane guidelines. RESULTS: Five studies (3 randomized trials, 1 cohort study and 1 prospective non- randomized controlled trial, totally 899 patients) were eligible for meta-analysis. The hazard ratio (HR) for TTP was 0.75 (95% CI: 0.48-1.03, p = 0.003) with significant heterogeneity (I2 = 82.7%) and for OS was 0.76 (95% CI: 0.47-1.05, p = 0.147) with slight heterogeneity (I2 = 47.9%). However, no covariate was found as independent predictor for better treatment efficacy. Hand-foot skin reaction, alopecia, rash/desquamation, diarrhea, hypertension, fatigue, anorexia, nausea and vomiting were common adverse events. CONCLUSIONS: TACE combined with sorafenib has potential efficacy for HCC.

Quantification of viable but nonculturable Salmonella spp. and Shigella spp. during sludge anaerobic digestion and their reactivation during cake storage.

AIMS: The presence of viable but nonculturable (VBNC) bacterial pathogens which often fail to be detected by cultivation and can regain the cultivability if the living conditions improve were reported. The objective of this study was to determine the occurrence of VBNC Salmonella spp. and Shigella spp. in the biosolids during anaerobic digestion and its reactivation during the cake storage. METHODS AND RESULTS: The occurrence of VBNC Salmonella spp. and Shigella spp. during mesophilic, temperature-phased, thermophilic anaerobic digestion of sewage sludge and the subsequent storage were studied by RT-qPCR and most probable number (MPN) method. The VBNC incidence of Salmonella spp. and Shigella spp. during thermophilic digestion was four orders of magnitude higher than those of mesophilic digestion. Accordingly, higher resuscitation ratio of VBNC pathogens was also achieved in thermophilic digested sludge. As a result, the culturable Salmonella typhimurium contents in thermophilic digested sludge after cake storage were two orders of magnitude higher than mesophilic digestion. Both quantitative PCR and reverse transcription quantitative PCR assay results showed the two bacterial counting numbers remained stable throughout the cake storage. CONCLUSIONS: The results indicate that the increase in the culturable Salmonella spp. and Shigella spp. after centrifugal dewatering was attributed to the resuscitation from the VBNC state to the culturable state. SIGNIFICANCE AND IMPACT OF THE STUDY: Thermophilic anaerobic digestion mainly induced Salmonella spp. and Shigella spp. into VBNC state rather than killed them, suggesting that the biological safety of sewage sludge by temperature-phased anaerobic digestion should be carefully assessed.

Double genomic control is not effective to correct for population stratification in meta-analysis for genome-wide association studies.

Meta-analysis of genome-wide association studies (GWAS) has become a useful tool to identify genetic variants that are associated with complex human diseases. To control spurious associations between genetic variants and disease that are caused by population stratification, double genomic control (GC) correction for population stratification in meta-analysis for GWAS has been implemented in the software METAL and GWAMA and is widely used by investigators. In this research, we conducted extensive simulation studies to evaluate the double GC correction method in meta-analysis and compared the performance of the double GC correction with that of a principal components analysis (PCA) correction method in meta-analysis. Results show that when the data consist of population stratification, using double GC correction method can have inflated type I error rates at a marker with significant allele frequency differentiation in the subpopulations (such as caused by recent strong selection). On the other hand, the PCA correction method can control type I error rates well and has much higher power in meta-analysis compared to the double GC correction method, even though in the situation that the casual marker does not have significant allele frequency difference between the subpopulations. We applied the double GC correction and PCA correction to meta-analysis of GWAS for two real datasets from the Atherosclerosis Risk in Communities (ARIC) project and the Multi-Ethnic Study of Atherosclerosis (MESA) project. The results also suggest that PCA correction is more effective than the double GC correction in meta-analysis.

Decreasing loss of cryopreserved-thawed rat islets by coculture with Sertoli cells.

OBJECTIVE: Cryopreserved-thawed rat islets were cocultured with Sertoli cells to examine whether they could decrease the loss and improve islet function. METHODS: Islets and Sertoli cells were harvested from the pancreas and the testis of Sprague-Dawley rats, respectively. Cryopreserved, stored islets were thawed and divided into groups of coculture with Sertoli cells versus single cells. We measured islets recovery rate and function. Apoptotic-related proteins and gene expressions were detected by Western blot and reverse-transcriptase polymerase chain reaction. Soluble factors secreted by Sertoli cells in to the supernate were detected by enzyme-linked immunosorbent assay. We compared islet graft survival times in diabetic mice. RESULTS: In contrast to the single culture controls, thawed islets cocultured with Sertoli cells exhibited improved morphology. Recovery rates and insulin secretion were significantly higher among coculture cells. Four soluble factors were detected in supernates from Sertoli cell cultures including transforming growth factor-ß, insulin-like growth factor-1, epidermal growth factor, and basic fibroblast growth factor. Expression of proapoptotic Bax and caspase 3, 7 were down-regulated while that of antiapoptotic Bcl-2 was up-regulated. Cotransplantation with Sertoli cells significantly prolonged islet graft survival. CONCLUSION: These results suggested that coculture with Sertoli cells significantly improved islet yields and function after thawing and depressed islet apoptosis.

Seventeen polymorphic microsatellite markers developed for the Javelin goby, Synechogobius hasta (Gobiidae).

Synechogobius hasta is an important commercial marine fish with distinctive features of rapid growth and short lifespan. We isolated and characterized 17 microsatellite markers for S. hasta using a (GT)(13)-enriched genomic library. Polymorphism was assessed in 48 individuals from a single population collected from the northern coastal waters of the Yellow Sea. The number of alleles per locus ranged from 2 to 23, with a mean of 11.3. The observed and expected heterozygosities ranged from 0.130 to 1.000 and from 0.123 to 0.939, with means of 0.758 and 0.774, respectively. Fourteen of 17 loci conformed to Hardy-Weinberg equilibrium and no significant linkage disequilibrium between locus pairs was detected. These microsatellite markers will be useful for population genetic structure analyses.

Effects of astragalosides on cultured islets after cryopreservation in rats.

OBJECTIVE: To explore the effects of AST (astragalosides) on cultured rat islet yield, purity, and function after cryopreservation in rats. METHODS: Pancreatic islets were isolated from 30 Sprague-Dawley rats using the standard technique of collagenase P digestion and discontinuous Ficoll gradient purification. After thaw, the islets were randomly divided into AST group and control group (n=15). Next, the islet cells were cultured in AST-containing medium or standard medium for 7, 14, and 21 days after cryopreservation and thaw. The quantity, purity, and survival rate were calculated in the two groups before and after culture. Then the in vitro and in vivo function was observed in diabetic rats after islet transplantation. RESULTS: The quantity and purity of islets had no difference between the two groups before culture (P>.05) while the difference after culture was significantly (P<.05). The survival rate of islets was 48% in AST group and 32% in the control group 21 days after thaw (P<.05). After 3 days, there was significantly a higher simulation index in the AST group than in the control group (P<.05). There was a significant difference in blood glucose and insulin concentrations between the groups after 3 days (P<.05). CONCLUSION: AST can be added to the culture medium to reduce the loss of islet cryopreservation and be intravenously injected to improve culture islet function in vitro and prolong islet graft survival in diabetic rats.

Efficacy of laser occlusion of posterior semicircular canal for benign paroxysmal positional vertigo: case report.

OBJECTIVE: To observe the long-term effect of laser occlusion of the posterior semicircular canal for benign paroxysmal positional vertigo. METHOD: Case report and review of the relevant world literature. RESULTS: We treated a patient with refractory benign paroxysmal positional vertigo using laser occlusion of the posterior semicircular canal, and achieved satisfactory results. Three months after the operation, the patient was able to lead a normal life. There was no recurrence over five years of follow up. CONCLUSION: To our knowledge, this is the first report in the world literature of a patient with refractory benign paroxysmal positional vertigo being treated with laser occlusion of the posterior semicircular canal. This method had long-term effectiveness, and may be one of the most effective methods of treating patients with refractory benign paroxysmal positional vertigo.

Boron neutron capture therapy for glioblastoma multiforme: interim results from the phase I/II dose-escalation studies

OBJECTIVE: The primary objective of these Phase I/II dose-escalation studies is to evaluate the safety of boronophenylalanine (BPA)-fructose-mediated boron neutron capture therapy (BNCT) for patients with glioblastoma multiforme (GBM). A secondary purpose is to assess the palliation of GBM by BNCT, if possible. METHODS: Thirty-eight patients with GBM have been treated. Subtotal or gross total resection of GBM was performed for 38 patients (median age, 56 yr) before BNCT. BPA-fructose (250 or 290 mg BPA/kg body weight) was infused intravenously, in 2 hours, approximately 3 to 5 weeks after surgery. Neutron irradiation was begun between 34 and 82 minutes after the end of the BPA infusion and lasted 38 to 65 minutes. RESULTS: Toxicity related to BPA-fructose was not observed. The maximal radiation dose to normal brain varied from 8.9 to 14.8 Gy-Eq. The volume-weighted average radiation dose to normal brain tissues ranged from 1.9 to 6.0 Gy-Eq. No BNCT-related Grade 3 or 4 toxicity was observed, although milder toxicities were seen. Twenty-five of 37 assessable patients are dead, all as a result of progressive GBM. No radiation-induced damage to normal brain tissue was observed in postmortem examinations of seven brains. The minimal tumor volume doses ranged from 18 to 55 Gy-Eq. The median time to tumor progression and the median survival time from diagnosis (from Kaplan-Meier curves) were 31.6 weeks and 13.0 months, respectively. CONCLUSION: The BNCT procedure used has been safe for all patients treated to date. Our limited clinical evaluation suggests that the palliation offered by a single session of BNCT is comparable to that provided by fractionated photon therapy. Additional studies with further escalation of radiation doses are in progress.