Search

A previous study indicated that synergy-based functional electrical stimulation (FES) may improve instantaneous upper-limb motor performance for stroke survivors. However, it remains unclear whether the improvements will sustain over time to achieve functional gains associated with a task-oriented training (TOT). This pilot study was designed to investigate whether there is any promising sign of functional benefits. A TOT protocol with repeated forward and lateral reaching movements assisted by synergy-based FES was conducted in 16 patients (9 FES, 7 Sham) with post-stroke hemiparesis. FES stimuli were applied to 7 upper-extremity muscles of elbow and shoulder during patient movements. Envelopes of stimuli were individualized by re-composing the muscle synergies extracted from a healthy subject. After a five-day training for one hour each day, synergy-based FES induced higher increases in Fugl-Meyer scores (6.67 ± 5.20) than did the Sham (2.00 ± 2.38, p 0.05). Peak velocity of forward reaching movements increased with a slope 73% steeper in FES group than Sham. In lateral reaching movements, the change in synergy similarity correlated with the change in elbow flexion for the FES group, but not the Sham group. Our results indicate that synergy-based FES therapy induced clinically traceable signs of improvements in poststroke motor performance. The muscle activation in patients also showed promising sign of alteration by FES. Results suggest that a larger scale clinical trial of synergy-based FES may be feasible towards an individualized therapeutic regimen.

Ferroptosis is a form of iron-dependent programmed cell death. Regulate ferroptosis in tumor cells is a novel treatment modality. The present study aimed to investigate ferroptosis-related long non-coding RNAs (lncRNAs) and construct a prognostic model for colon adenocarcinoma (COAD). RNA- sequencing data and ferroptosis-related genes were obtained from The Cancer Genome Atlas database and FerrDb database. COAD patients were randomly assigned to training- and validation groups. The Least Absolute Shrinkage and Selection Operator regression and Cox regression model were used to determine and develop a predictive model. The model was corroborated using the validation group and the entire group. In total, 259 ferroptosis-related genes and 905 ferroptosis-related LncRNAs were obtained. Cox model revealed and constructed seven ferroptosis-related LncRNAs signature (LINC01503, AC004687.1, AC010973.2, AP001189.3, ARRDC1-AS1, OIP5-AS1, and NCK1-DT). Patients were assigned into two groups according to the median risk score. Kaplan–Meier survival curves showed that overall survival between high- and low-risk groups was statistically significant (P

Functional electrical stimulation (FES) is capable of activating muscles that are under-recruited in neurological diseases, such as stroke. Therefore, FES provides a promising technology for assisting upper-limb motor functions in rehabilitation following stroke. However, the full benefits of FES may be limited due to lack of a systematic approach to formulate the pattern of stimulation. Our preliminary work demonstrated that it is feasible to use muscle synergy to guide the generation of FES patterns.In this paper, we present a methodology of formulating FES patterns based on muscle synergies of a normal subject using a programmable multi-channel FES device. The effectiveness of the synergy-based FES was tested in two sets of experiments. In experiment one, the instantaneous effects of FES to improve movement kinematics were tested in three patients post ischemic stroke. Patients performed frontal reaching and lateral reaching tasks, which involved coordinated movements in the elbow and shoulder joints. The FES pattern was adjusted in amplitude and time profile for each subject in each task. In experiment two, a 5-day session of intervention using synergy-based FES was delivered to another three patients, in which patients performed task-oriented training in the same reaching movements in one-hour-per-day dose. The outcome of the short-term intervention was measured by changes in Fugl-Meyer scores and movement kinematics. Results on instantaneous effects showed that FES assistance was effective to increase the peak hand velocity in both or one of the tasks. In short-term intervention, evaluations prior to and post intervention showed improvements in both Fugl-Meyer scores and movement kinematics. The muscle synergy of patients also tended to evolve towards that of the normal subject. These results provide promising evidence of benefits using synergy-based FES for upper-limb rehabilitation following stroke. This is the first step towards a clinical protocol of applying FES as therapeutic intervention in stroke rehabilitation.

Yes-associated protein (YAP) has been identified as a key driver for epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance. Inhibition of YAP expression could be a potential therapeutic option for treating non-small-cell lung cancer (NSCLC). Herein, a nanococktail therapeutic strategy is proposed by employing amphiphilic and block-dendritic-polymer-based nanoparticles (NPs) for targeted co-delivery of EGFR-TKI gefitinib (Gef) and YAP-siRNA to achieve a targeted drug/gene/photodynamic therapy. The resulting NPs are effectively internalized into Gef-resistant NSCLC cells, successfully escape from late endosomes/lysosomes, and responsively release Gef and YAP-siRNA in an intracellular reductive environment. They preferentially accumulate at the tumor site after intravenous injection in both cell-line-derived xenograft (CDX) and patient-derived xenograft (PDX) models of Gef-resistant NSCLC, resulting in potent antitumor efficacy without distinct toxicity after laser irradiation. Mechanism studies reveal that the cocktail therapy could block the EGFR signaling pathway with Gef, inhibit activation of the EGFR bypass signaling pathway via YAP-siRNA, and induce tumor cell apoptosis through photodynamic therapy (PDT). Furthermore, this combination nanomedicine can sensitize PDT and impair glycolysis by downregulating HIF-1α. These results suggest that this stimuli-responsive dendritic-polymer-based nanococktail therapy may provide a promising approach for the treatment of EGFR-TKI resistant NSCLC.

Dehydroepiandrosterone sulphate (DHEAS), the most plentiful circulating adrenal hormone, may be considered as a marker of the onset of adrenarche and is involved in pubertal development and metabolic disorders.The objective of this study is to determine the genetic and environmental influences on the variation of basal DHEAS levels and pubertal development in pubertal girls.Three hundred and sixty twin girls aged 6-18-years were enrolled, consisting of 132 monozygotic pairs and 48 dizygotic pairs. Anthropometric and sexual characteristics were examined. Serum DHEAS was measured by RIA. Estimates of genetic and environmental components of variance were based on the theory of normal maximum likelihood in Mx package.Serum DHEAS concentrations of PH-II and PH-III were significantly higher than Tanner stage PH-I (p .05) and maintained higher levels in PH-IV ∼ V. Heritability of serum DHEAS estimated by model-fitting on data from 180-pairs of twins is 0.61 (0.52-0.70), the rest of the variance in DHEAS levels could be explained by unique environmental influences and age. The heritabilities of DHEAS in two pubertal sub-groups (PH-I and PH-II-V) are 0.82 (0.71-0.90) and 0.63 (0.52-0.74), respectively. The heritability index of menarche, breast development and pube development are 0.71, 0.35 and 0.45, respectively.Serum DHEAS concentrations of pubertal girls are mainly influenced by genetic factors, especially during the period of adrenarche. The results stress the importance of research into the genetic regulation of the endocrine regulators involved in adrenarche and related metabolic disorders in girls.

Objectives: In 2005, China acceded to the World Health Organization Framework Convention on Tobacco Control (WHO FCTC), the foundation for the global fight against tobacco. Certain cities in China have established local regulations to control tobacco use ahead of national policy, however, without the enforcement of statutory law, some of these regulations are merely lip service. The aim of the study was to assess the effects of city policy on smoking prevalence and on second-hand smoke (SHS) exposure status among non-smokers in Changchun City. Methods: A cross-sectional survey covering a multiple-stage, representative sample of the urban population aged ≥15 years was conducted between 1 Dec 2013 and 31 Jan 2014. The WHO and the US Centers for Disease Control and Prevention developed the questionnaires used, which included demographic characteristics, smoking behaviors and SHS exposure status. Results: Overall cigarette smoking prevalence was 23.5%, daily cigarette smoking prevalence was 21.2%. Smoking prevalence and cigarettes consumed per day was higher among men (p &lt, 0.05) and those aged 45–64 years (p &lt, 0.05). Among current smokers, 8.1% planned to quit within 12 months, 53.4% had no intention of quitting. Overall SHS exposure prevalence was 41.9% (workplace) and 34.1% (at home) over the previous 30 days. The weighted workplace SHS exposure prevalence increased with age. Conclusions: The high proportion of smokers with no intention of quitting and the high level of SHS exposure may constitute one of the most significant barriers to successful smoking cessation in the city. A continued drive to promote full implementation of the WHO FCTC is still needed.

To compare the differences in the complete genome sequence between mumps epidemic strain and mumps vaccine strain S79 isolated in Zhejiang province.A total of 4 mumps epidemic strains, which were separated from Zhejiang province during 2005 to 2010, named as ZJ05-1, ZJ06-3, ZJ08-1 and ZJ10-1 were selected in the study. The complete genome sequences were amplified using RT-PCR. The genetic differences between vaccine strain S79 and other genotype strains were compared; while the genetic-distance was calculated and the evolution was analyzed.The biggest difference between the 4 epidemic strains and the vaccine strain S79 was found on the membrane associated protein gene; whose average nucleotide differential number was 42.5 +/- 3.0 and the average variant ratio was 13.6%; while the mean amino acid differential number was 12.8 +/- 1.5 and the average variant ratio was 22.4%. The smallest difference among the 4 epidemic strains and the vaccine strain was found in stromatin genes, whose average nucleotide differential number was 73.8 +/- 2.5 and the average variant ratio was 5.9%; while the mean amino acid differential number was 3.0 +/- 0.8 and the average variant ratio was 0.8%. The dn/ds value of the stromatin genes of the 4 epidemic strains reached the highest, as 0.6526; but without any positive pressure (dn/ds1, chi2 = 0.87, P0.05). There were mutations happened on the known antigen epitope, as 8th amino acid of membrane associated protein genes and on the 336th and 356th amino acid of hemagglutinin/neuraminidase proteins. Compared with the vaccine strain, the glycosylation sites of ZJ05-1, ZJ06-3, ZJ08-1 and ZJ10-1 increased 1, 1, 2 and 2 respectively. The complete amino acid sequence of all strains showed that there were 17 characteristic sites found on the genotype-F mumps strain. Within the complete genome, the genetic-distance between epidemic strains and vaccine strains in Zhejiang province (0.071) was significantly larger than the genetic-distance between strains in Yunnan province (0.013); the difference showing statistical significance (t = 4.14, P0.05). Except nucleocapsid protein genes, all the genes shared similar evolution tree.There were significant differences found in the genes between mumps epidemic strain and mumps vaccine in Zhejiang province.

To evaluate the long-term immunogenicity and effectiveness of live attenuated hepatitis A (HA) vaccine (H2 strain) after one dose injection, through a 15 years' follow up observation.A total of 220 children with negative anti-HAV antibody (aged 1-3 y) were involved and followed up in Jiaojiang district, Taizhou city, Zhejiang province. Indicators would include seroconversion and geometric mean titer (GMT) levels after inoculation the vaccine with single dose at 2 m, 12 m, 6 years, 10 years and 15 years. Epidemiological observation was carried out within the 15 years to evaluate the relationship between vaccine coverage, the incidence of HA and the overall effectiveness. In the studied population, serum was tested by ELISA (calibrated by WHO international reference) and ABBOTT Axsym HAVAB mEIA.Seroconversion rates were found to be 98.6% and 81.3% after 2 months and 15 years of inoculation and slowly decreased. GMT level was 128 mIU/ml after 15 years, significantly higher than the required protective level of 20 mIU/ml, recommended by WHO experts. Effectiveness through the 15-year follow up program showed a significant correlation between vaccine coverage and incidence of HA in 1-15 years aged group (Kendall-Rank test, τ =-0.931, P0.01). There was no HA case seen among the observed accumulated 236 413 person-year vaccines, compared to 4 HA cases discovered in the 27 206 person-year of the non-vaccinees. The overall protective rate reached 100%. Through a mass vaccination program on children, the whole population established an immune-defence to enable the incidence of HA decreased by 96.7%.The long-term immunogenicity and effectiveness of live attenuated hepatitis A vaccine (H2 strain) after one dose injection could last as long as 15 years.

Live attenuated hepatitis A vaccine (H2 strain) is widely applied in prevention of hepatitis A epidemic in China and other countries now. It is essential to observe and confirm the vaccine immune efficacy, population antibody level and its persistent efficacy after mass immunization.A total of 220 children with negative anti-HAV antibody (aged 1 - 3 years) were taken for follow-up assay to observe seroconversion and geometric mean titre (GMT) level 2 months, 12 months, 6 years, and 10 years after inoculation. Another survey sampled from subjects of different age groups (3, 6, 9, 15, 18, 25 and 35 years) to compare anti-HA antibody positive rate before and after inoculation performed 10 years previously. Epidemiological observations were taken for 10 years to evaluate the relationship between vaccine coverage and hepatitis A morbidity. Serum antibody to HAV was detected by enzyme linked immunoassay (ELISA, calibrated by WHO international reference) and ABBOTT Axsym HAVAB microparticle enzyme immunoassay.Seroconversion in follow-up assay 2 months and 10 years after inoculation was 98.6% and 80.2% respectively. For children, the vaccination anti-HA antibody positive rates were significantly different before and after 10 years, 7.69% cf 70.45% (aged 3 years) and 52.58% cf 71.78% (aged 18 years). When vaccine coverage rose from 57% to 74%, there were no any HA epidemics. When vaccine coverage reached 85%, there were no any HA cases. With vaccine coverage between 85% and 91%, there were no any HA cases in cohorts from the age of 1 year to 15 years during the 10 years.Live attenuated hepatitis A vaccine has an obvious long-term effectiveness in prevention and control of HA epidemics through mass vaccination.

BackgroundPrevious trials have shown that zinc supplementation can decrease the risk of diarrhea, pneumonia, and malaria in children; however, the effects of zinc supplementation on mortality remain unclear. This study aimed at evaluating the benefits and risks of zinc supplementation on both total mortality and cause-specific mortality.Methodology and principal findingsWe searched PubMed, EmBase, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials in preschool children reporting total mortality or cause-specific mortality. Relative risk (RR) was used as a measure of the effect of zinc supplementation on the risk of mortality using a random effect model. Of the 1,520 identified articles, we included 8 trials reporting data on 87,854 children. Overall, zinc supplementation had no effect on total mortality (RR, 0.76; 95% CI: 0.56-1.04; P = 0.084), diarrhea-related mortality (RR, 0.80; 95% CI: 0.53-1.20; P = 0.276), pneumonia-related mortality (RR, 0.52; 95% CI: 0.11-2.39; P = 0.399), malaria-related mortality (RR, 0.90; 95% CI: 0.77-1.06; P = 0.196), or other causes of mortality (RR, 0.98; 95% CI: 0.67-1.44; P = 0.917). Subgroup analysis indicated that zinc supplementation was associated with a reduction in total mortality risk if the participants were boys, aged greater than 12 months, and the duration of the follow-up period was less than 12 months.Conclusions/significanceZinc supplementation does not have an effect on total mortality, diarrhea-related mortality, pneumonia-related mortality, malaria-related mortality, or other causes of mortality. Subgroup analysis suggested that zinc supplementation can effectively reduce the risk of total mortality if the participants were boys, aged greater than 12 months, and the duration of the follow-up period was less than 12 months.

AIM: To investigate the hotspots, direction, and the time course of evolution of hepatitis A virus in the process of consecutive cell culture passage in human KMB17 diploid cells. METHODS: Wild type hepatitis A virus H2w was serially propagated in KMB17 cells until passage 30, and the full-length genomes of H2w and its six chosen progenies were determined by directly sequencing RT-PCR products amplified from viral genomic RNA. Alignment comparison of sequences from H2w with its six progenies and phylogenetic analysis of the whole VP1 region from H2w, progenies of H2w, and other cell culture adapted hepatitis A virus were then carried out to obtain data on the molecular evolution of hepatitis A virus in the process of consecutive passage in KMB17 cells. RESULTS: Most of the mutations occurred by passage 5 and several hotspots related to adaptation of the virus during cell growth were observed. After that stage, few additional mutations occurred through the remaining duration of passage in KMB17 cells except for mutation in the virulence determinants, which occurred in the vicinity of passage 15. The phylogenetic analysis of the whole VP1 region suggested that the progenies of H2w evolved closely to other cell culture adapted hepatitis A virus, i.e. MBB, L-A-1, other than its progenitor H2w. CONCLUSION: Hepatitis A virus served as a useful model for studying molecular evolution of viruses in a given environment. The information obtained in this study may provide assistance in cultivating the next generation of a seed virus for live hepatitis A vaccine production.