Stretchable, dynamic covalent polymers for soft, long-lived bioresorbable electronic stimulators designed to facilitate neuromuscular regeneration.

Bioresorbable electronic stimulators are of rapidly growing interest as unusual therapeutic platforms, i.e., bioelectronic medicines, for treating disease states, accelerating wound healing processes and eliminating infections. Here, we present advanced materials that support operation in these systems over clinically relevant timeframes, ultimately bioresorbing harmlessly to benign products without residues, to eliminate the need for surgical extraction. Our findings overcome key challenges of bioresorbable electronic devices by realizing lifetimes that match clinical needs. The devices exploit a bioresorbable dynamic covalent polymer that facilitates tight bonding to itself and other surfaces, as a soft, elastic substrate and encapsulation coating for wireless electronic components. We describe the underlying features and chemical design considerations for this polymer, and the biocompatibility of its constituent materials. In devices with optimized, wireless designs, these polymers enable stable, long-lived operation as distal stimulators in a rat model of peripheral nerve injuries, thereby demonstrating the potential of programmable long-term electrical stimulation for maintaining muscle receptivity and enhancing functional recovery.

Efficacy of Chinese herbal medicine for lumbar disc herniation: a systematic review of randomized controlled trials.

OBJECTIVE: This is a review of the effects of Chinese herbal medicine (CHM) used alone to treat lumbar disc herniation (LDH). METHODS: A literature search of the following electronic databases from their inception to February 2013 was conducted: Chinese Biomedical databases, Chinese National Knowledge Infrastructure, Wanfang Database, China Science and Technology Journal Database, Cochrane Library, Web of Science, MEDLINE, and EMBASE. Randomized controlled trials where CHM had been used to treat LDH were selected. Data extraction, quality assessment, and data analysis were carried out by two independent reviewers. RESULTS: Of the 2415 studies identified, eight with complete data on 1146 patients were selected. The methodological quality was poor in all trials. Five studies reported that CHM was better than Western Medicine [OR = 2.81, 95% CI (1.27, 6.18); OR = 3.34, 95% CI (1.92, 5.79); OR = 2.22, 95% CI (1.08, 4.57); OR = 6.67, 95% CI (1.34, 33.28); and OR = 1.94, 95% CI (1.23, 3.06)]. Two studies reported that the clinical outcome was better in CHM groups than in physiotherapy and placebo groups, [OR = 3.02, 95% CI (1.08, 8.46); and OR = 2.67, 95% CI (1.26, 5.64), respectively], whereas one study reported no difference between CHM and physiotherapy groups. One study reported that CHM resulted in higher Japanese Orthopedic Association scores [MD = 7.78, 95% CI (6.67, 8.89)] than in a control group and another that participants treated with CHM had lower Visual Analogue Scale scores [MD = -0.72, 95% CI (- 0.86, -0.58)] than those in a control group. Three studies reported that the adverse effects of CHM and Western Medicine did not differ significantly [OR = 0.10, 95% Cl (0.01, 1.85); OR = 0.19, 95% CI (0.01, 4.07); and OR = 0.07, 95% CI (0.00, 1.32)]. CONCLUSION: CHM may be more effective than other interventions for LDH; however, methodological weaknesses in the studies assessed in this review prevent a definitive conclusion. More high-quality large-scale studies are required to clarify this matter.

[Analysis of variance of repeated data measured by water maze with SPSS].

OBJECTIVE: To introduce the method of analyzing repeated data measured by water maze with SPSS 11.0, and offer a reference statistical method to clinical and basic medicine researchers who take the design of repeated measures. METHODS: Using repeated measures and multivariate analysis of variance (ANOVA) process of the general linear model in SPSS and giving comparison among different groups and different measure time pairwise. RESULTS: Firstly, Mauchly's test of sphericity should be used to judge whether there were relations among the repeatedly measured data. If any (P

[Effect of TX0201 on expression of the apoptosis signal transduction molecule caspase-3 and apoptosis associated genes bcl-2 and bax mRNA in brain tissue of rat analogue model of Alzheimer's disease].

OBJECTIVE: To study the mechanism of TX0201, an effective fraction extracted from Tiaoxin recipe in regulating apoptosis associated genes in brain tissue of rat analogue model of Alzheimer's disease (AD) induced by beta-amyloid protein 25-35 (Abeta 25-35). METHODS: The model of AD was induced by bilateral amygdala injection of Abeta 25-35 to study the spatial memory capacity using Morris water maze test, and by means of RT-PCR and immunohistochemistry assay, the expressions of beta-amyloid precursor protein (APP), apoptosis correlative genes (bcl-2, bax), and apoptosis signal transduction molecule (Caspase-3) in the brain, and the effect of TX0201 on expressions of these genes were examined. RESULTS: In AD model group, the spatial capacity was damaged significantly. Caspase-3 and the expression of APP mRNA and bax/bcl-2 mRNA were increased in the cortex and hippocampus; TX0201 ameliorated all the pathologic changes mentioned above. CONCLUSION: TX0201 could improve the oriented learning and memory capacity in AD rats by decreasing bax/bcl-2 and down-regulating Caspase-3 to reduce neurocyte apoptosis, suggesting that effective regulation of neuron apoptosis associated genes may be one of the mechanisms of TX0201.

[Effects of recipes for replenishing qi and activating blood on senescence related gene expressions in the liver of aging rats].

OBJECTIVE: To observe the effects of recipes for replenishing qi and activating blood on p16, p21, proliferating cell nuclear antigen (PCNA), cyclin D1 and cyclin E gene expressions in the liver of aging rats. METHODS: A recipe for replenishing qi and a recipe for activating blood were administered to aging rats respectively, and the effects of the above recipes on the expressions of senescence related genes (p16, p21, PCNA, cyclin D1 and cyclin E) were examined by RT-PCR and Western blotting methods. RESULTS: The expressions of p16, p21 and cyclin D1 mRNAs and proteins in the liver of the untreated aging rats were up-regulated, while the expressions of PCNA and cyclin E mRNAs and proteins decreased. As compared with the untreated aging rats, both recipes could down-regulate the expressions of cyclin D1 mRNA and protein and up-regulate the expressions of cyclin E mRNA and protein, but had no obvious effects on the expressions of mRNAs and proteins of p16, p21 and PCNA. CONCLUSION: Recipes for replenishing qi and activating blood can improve the liver cell proliferation of aging rats via down-regulating the expressions of cyclin D1 mRNA and protein and up-regulating the expressions of cyclin E mRNA and protein.

Electroacupuncture attenuates morphine withdrawal signs and c-Fos expression in the central nucleus of the amygdala in freely moving rats.

Experimental efforts for understanding the mechanisms of electroacupuncture (EA) for opiate addiction are partially hampered by restraint stress. In unrestrained animals, it is difficult to perform EA stimulation at acupuncture points frequently selected on the four limbs. The present study was performed to evaluate the effect of EA at the acupuncture point Shen-Shu (BL.23) on morphine withdrawal signs and c-Fos expression of the amygdala in freely moving rats or restrained rats. We applied immunohistochemistry to detect c-Fos-positive nuclei. Corticosterone levels and behavioral responses were measured during EA stimulation. The needles were bilaterally inserted and fixed at BL.23, and 100-Hz electric stimulation was conducted 30 min before naloxone-precipitated withdrawal. In both freely moving rats and restrained rats, EA significantly reduced the signs of morphine withdrawal. Notably, EA stimulation in freely moving rats attenuated c-Fos expression in the central nucleus of the amygdala while EA in restrained animals increased this response. In addition, the restrained rats emitted greater levels of vocalization and facial expression than freely moving rats during EA stimulation. Corticosterone levels were also significantly higher in restrained animals after EA stimulation. The new EA paradigm demonstrated in the present study might help the analysis of certain physiological responses induced by EA that would otherwise have been hindered by restraint stress.

[Effect of recipes replenishing qi and activating blood on cell proliferation and apoptosis in the liver of aging rats].

OBJECTIVE: To observe the effect of recipes replenishing qi and activating blood on cell proliferation and apoptosis in the liver of natural aging rats. METHODS: Natural aging rats were under administration of recipes replenishing qi or activating blood for 4 months. The liver of the rats was prepared into cell suspension for determination of cell proliferation and apoptosis with PI-staining and flow cytometer. RESULTS: (1) Compared with those of the young rats, the cells in G(0)-G1 phase in the liver tissue of aging rats were increased (P< 0.01), and apoptosis cells were increased (P< 0.01), while the cells in S and G2-M phases were decreased (P< 0.01). (2) Compared with those of the aging rats, the cells in G(0)-G1 phase in the liver tissue of aging rats administered recipes replenishing qi or activating blood were decreased (P< 0.01), and it was more obvious in activating blood group than in replenishing qi group (P< 0.01); the cells in S and G2-M phases were increased (P< 0.01) and there was no significant difference between the activating blood group and the replenishing qi group (P> 0.05). (3) The apoptosis cells in replenishing qi or activating blood group were decreased significantly (P< 0.01), and the effect of replenishing qi was better than that of activating blood (P< 0.01). CONCLUSION: (1) Cell proliferation is decreased and apoptosis is increased in the liver tissue of natural aging rats. (2) Recipes replenishing qi or activating blood can accelerate cell proliferation in the liver tissue of natural aging rats, and the effect of activating blood was slightly stronger than that of replenishing qi. (3) Recipes replenishing qi or activating blood can inhibit cell apoptosis in the liver tissue of natural aging rats, and the effect of replenishing qi was better than that of activating blood.

[Effect of heart benefiting recipe in controlling IL-1beta, IL-6 and APPmRNA expression in brain of beta-amyloid protein induced rat model of dementia].

OBJECTIVE: To investigate the neuro-immune regulatory mechanism of Heart Benefiting recipe (HBR), an effective recipe for treatment of Alzheimer's disease (AD). METHODS: Using immunohistochemical and RT-PCR methods, the neuro-immunological pathological changes in the AD rat model induced by beta-amyloid protein (A beta1-40) via lateral cerebral ventricle injection, including mainly the glial fibrillary acidic protein expression and inflammatory cytokines IL-1beta, IL-6mRNA and beta-amyloid protein precursor (APPmRNA) gene expression were studied. And the effects of HBR on these parameters were observed. RESULTS: Deposition of A beta in cerebral tissue could induce activation of stellate glial cells and abnormal increased levels of inflammatory cytokines (IL-1beta and IL-6mRNA), also the elevation of APPmRNA level. HBR could effectively control the above-mentioned pathological changes. CONCLUSION: HBR could effectively control the inflammation and the A beta immune cascade reaction in brain of AD patients, it is one of the important therapeutic mechanisms of the recipe.

[Comparative study on the regulatory effects on senescence related cell cycle gene expression by TCM principles of tonifying shen, invigorating pi benefiting qi, and activating blood circulation].

OBJECTIVE: To compare the effects of TCM therapeutic principles of tonifying Shen (TS), benefiting Qi (BQ), invigorating Pi (IP) and activating blood circulation (ABC) herbs in regulating the gene expression in senescence related cell cycle. METHODS: Drug sera containing TCM herbs of the above-mentioned principles were used to treat the aged human diploid fibroblast cell line 2BS. The effect of TCM on the senescence related cell cycle and its related gene expression (P16INK4, Cyclin D1 and PCNA) were examined by means of cell proliferative doublings, flow cytometry, RT-PCR and Western blot analysis. RESULTS: TCM herbs of TS and BQ could improve the cell cycle, down-regulate the P16 and Cyclin D1 mRNA/protein expression, up-regulate PCNA mRNA/protein expression, while TCM herbs of IP and ABC showed insignificant effect on these indexes. CONCLUSION: TCM herbs of TS and BQ have effect in improving cell cycle, it may be achieved through promoting the P16 pathway of gene expression.

[Establishment of analogous oxidative damaged Alzheimer's disease rat model and effect of tiaoxin recipe on it].

OBJECTIVE: To establish a convenient, economical and practical analogous oxidative damaged Alzheimer's disease rat model (AD model) for exploring the effect of Tiaoxin Recipe (TXR) on the spatial memory capacity and beta-amyloid protein (A beta) deposition in the model. METHODS: The AD model was established by left ventricular injection of DHF-FeCl3-ADP. Spatial memory and learning capacity of the model rat was observed by Morris water maze method, A beta deposition in its cerebral cortex was observed by immunohistochemistry, and the effect of TXR was analysed. RESULTS: Compared with the normal group, the spatial memory capacity in the model group was obviously decreased, with A beta widely deposited in cortex, immunohistochemical examination showed that the number of A beta positive cells and their mean optic density significantly increased. TXR displayed significantly improving effect on the above-mentioned changes. CONCLUSION: The oxidative damaged model could not only express the clinical characteristics (short-term memory impairment), but also partially reflex the pathological changes (A beta deposition) of AD, is an economical and practical analogous AD model. TXR has the effects of improving spatial memory impairment and lowering A beta deposition in the AD model rats.