Research progress of the effective active ingredients of Astragalus mongholicus in the treatment of diabetic peripheral neuropathy.

Diabetic peripheral neuropathy (DPN) is one of the most prevalent consequences of diabetes, with a high incidence and disability rate. The DPN's pathogenesis is extremely complex and yet to be fully understood. Persistent high glucose metabolism, nerve growth factor deficiency, microvascular disease, oxidative stress, peripheral nerve cell apoptosis, immune factors, and other factors have been implicated in the pathogenesis of DPN. Astragalus mongholicus is a commonly used plant used to treat DPN in clinical settings. Its rich chemical components mainly include Astragalus polysaccharide, Astragalus saponins, Astragalus flavones, etc., which play a vital role in the treatment of DPN. This review aimed to summarize the pathogenesis of DPN and the studies on the mechanism of the effective components of Astragalus mongholicus in treating DPN. This is of great significance for the effective use of Chinese herbal medicine and the promotion of its status and influence on the world.

Age and sex-specific differences of mindfulness traits with measurement invariance controlled in Chinese adult population: A pilot study.

Objectives: To examine the relationships of age and sex with mindfulness traits among Chinese adults with controlling for measurement invariance. Methods: A total of 1777 participants completing the Five-Facet Mindfulness Questionnaire were included for analysis. Their age and sex information were also collected. Descriptive analysis, Pearson's Chi-Square test and analysis of variance were performed to test the age- and sex-specific differences, measurement invariance was examined by confirmatory factor analysis. Results: Excellent data fit to the model indicated configural, metric, and scalar invariance across age and sex. Participants aged 60 or above scored significantly higher in dimensions of acting with awareness, nonjudging of inner experience, nonreactivity to inner experience, and the total scores than younger individuals, who had higher scores in the observing domain. In addition, females scored higher in describing and observing than males, while the latter had higher score in nonreactivity to inner experience. Conclusions: The Five-Facet Mindfulness Questionnaire Mindfulness showed acceptable measurement invariance across age and sex in Chinese adult population. The old and the young differs in the traits of awareness, observing, nonjudging of inner experience, nonreactivity to inner experience and the total mindfulness level, while males and females varied in describing, observing and nonreactivity to inner experience. Individual differences should be considered and well addressed in future studies on mindfulness.

A GLP-2 Analogue Protects SH-SY5Y and Neuro-2a Cells Against Mitochondrial Damage, Autophagy Impairments and Apoptosis in a Parkinson Model.

Glucagon-like peptide-2 (GLP-2) is a peptide hormone that belongs to the glucagon-derived peptide family. We have previously shown that analogues of the sister hormone Glucagon-like peptide-1 (GLP-1) showed neuroprotective effects. Here we investigated the effect of a GLP-2 agonist in a cell model of Parkinson's disease (PD) created by treating SH-SY5Y or Neuro-2a cells with 1-Methyl-4-phenyl-pyridine ion (MPP+). Cell viability and cell cytotoxicity was detected by MTT and LDH assays, respectively. The protein expression levels of mitochondrial, autophagy and apoptotic biomarkers including PGC-1α, Mfn2, IRE1, ATG7, LC3B, Beclin1 and Bcl-2 were detected by western blot. Mitochondrial superoxide was detected by MitoSOX Red. In addition, mitochondrial morphology, autophagosome and apoptotic corpuscles were observed by transmission electron microscope (TEM). We found that the GLP-1 and the GLP-2 agonists both protect cells against mitochondrial damage, autophagy impairments and apoptosis induced by MPP+both in SH-SY5Y and Neuro-2a cells. Cell signaling for mitogenesis was enhanced, and oxidative stress levels much reduced by the drugs. This demonstrates for the first time the neuroprotective effects of a GLP-2 analogue in PD cellular models, in which oxidative stress, autophagy and apoptosis play crucial roles. The protective effects were comparable to those seen with the GLP-1 analogue liraglutide. The results suggest that not only GLP-1, but also GLP-2 has neuroprotective properties and may be useful as a novel treatment of PD.

Toward Defect-Free Doping by Self-Assembled Molecular Monolayers: The Evolution of Interstitial Carbon-Related Defects in Phosphorus-Doped Silicon.

Self-assembled molecular monolayer (SAMM) doping on semiconductors has been widely appraised for its advantages of doping nanoelectronic devices for applications in the complementary metal-oxide-semiconductor transistor (CMOS) industry. However, defects introduced by SAMM-doping will limit the performance of the devices. Previously, we have found that SAMM-doping can bring carbon impurities into the silicon substrate and these unwanted carbon impurities can deactivate phosphorus dopants by forming an interstitial carbon (Ci)-substitutional phosphorus (Ci-Ps) complex. Herein, to develop a defect-free SAMM-doping process, the generation and annihilation of Ci-related defects are investigated by extending the thermal annealing time from 2 to 10 min using secondary ion mass spectrometry and deep-level transient spectroscopy. The results show that the concentration of Ci-related carbon defects is lower after a longer time of thermal annealing, although a longer annealing time actually introduces a higher concentration of carbon impurities into Si. This observation indicates that interstitial carbon evolves into substitutional carbon (Cs) that is electrically inactive during the thermal annealing process. A defect-free SAMM-doping process may be developed by an appropriate post-annealing process.

Traditional Chinese medicine (TCM) collaborative care for patients with axial spondyloarthritis (AcuSpA): protocol for a pragmatic randomized controlled trial.

BACKGROUND: Axial spondyloarthritis (AxSpA) is a chronic disease which results in fatigue, pain, and reduced quality of life (QoL). Traditional Chinese medicine (TCM), especially acupuncture, has shown promise in managing pain. Although a TCM collaborative model of care (TCMCMC) has been studied in cancer, there are no randomized controlled trials investigating TCM in AxSpA. Therefore, we will conduct a pragmatic trial to determine the clinical effectiveness, safety, and cost-effectiveness of TCMCMC for patients with AxSpA. We define TCMCMC as standard TCM history taking and physical examination, acupuncture, and TCM non-pharmacological advice and communications with rheumatologists in addition to usual rheumatologic care. The purpose of this paper is to describe the rationale for and methodology of this trial. METHODS/DESIGN: This pragmatic randomized controlled trial will recruit 160 patients who are diagnosed with AxSpA and have inadequate response to non-steroidal anti-inflammatory drugs (NSAIDs). Simple randomization to usual rheumatologic care or the intervention (TCMCMC) with a 1:1 allocation ratio will be used. Ten 30-min acupuncture sessions will be provided to patients assigned to the TCMCMC arm. All participants will continue to receive usual rheumatologic care. The primary endpoint - spinal pain - will be evaluated at week 6. Secondary endpoints include clinical, quality of life, and economic outcome measures. Patients will be followed up for up to 52 weeks, and adverse events will be documented. DISCUSSION: This trial may provide evidence regarding the clinical effectiveness, safety, and cost-effectiveness of a TCMCMC for patients with AxSpA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03420404 . Registered on 14 February 2018.

MNE Scan: Software for real-time processing of electrophysiological data.

BACKGROUND: Magnetoencephalography (MEG) and Electroencephalography (EEG) are noninvasive techniques to study the electrophysiological activity of the human brain. Thus, they are well suited for real-time monitoring and analysis of neuronal activity. Real-time MEG/EEG data processing allows adjustment of the stimuli to the subject's responses for optimizing the acquired information especially by providing dynamically changing displays to enable neurofeedback. NEW METHOD: We introduce MNE Scan, an acquisition and real-time analysis software based on the multipurpose software library MNE-CPP. MNE Scan allows the development and application of acquisition and novel real-time processing methods in both research and clinical studies. The MNE Scan development follows a strict software engineering process to enable approvals required for clinical software. RESULTS: We tested the performance of MNE Scan in several device-independent use cases, including, a clinical epilepsy study, real-time source estimation, and Brain Computer Interface (BCI) application. COMPARISON WITH EXISTING METHOD(S): Compared to existing tools we propose a modular software considering clinical software requirements expected by certification authorities. At the same time the software is extendable and freely accessible. CONCLUSION: We conclude that MNE Scan is the first step in creating a device-independent open-source software to facilitate the transition from basic neuroscience research to both applied sciences and clinical applications.

Explore the effects of Huang-Lian-Jie-Du-Tang on Alzheimer's disease by UPLC-QTOF/MS-based plasma metabolomics study.

Alzheimer's disease (AD) is a progressive neurodegenerative disease with neither definitive pathogenesis nor effective treatment method so far. Huang-Lian-Jie-Du-Tang (HLJDT) is a classic formula of traditional Chinese medicine (TCM) proven to have ameliorative effects on learning and memory deficits of dementia. Morris water maze (MWM) test and pathology analysis have demonstrated that HLJDT could ameliorate learning and memory deficits in AD mouse model, which may act via its anti-neuroinflammation properties. According to our previous studies, an UPLC-QTOF/MS-based metabolomics approach was performed to explore the potential mechanisms of HLJDT on preventing AD. As a result, a total of 23 potential metabolites (VIP >1, |Pcorr| >0.58, CUFjk excludes 0, P < 0.05) contributing to AD progress were identified. The metabolic pathway analysis with MetPA revealed that glycerophospholipid metabolism, sphingolipid metabolism, arachidonic acid metabolism, linoleic acid metabolism and tryptophan metabolism were disturbed in mouse model of AD. After HLJDT treatment, 14 metabolites were restored back to the control-like levels.

Metabolomics-based mechanisms exploration of Huang-Lian Jie-Du decoction on cerebral ischemia via UPLC-Q-TOF/MS analysis on rat serum.

ETHNOPHARMACOLOGICAL RELEVANCE: Huang-Lian Jie-Du decoction (HLJDD), a traditional formula of Chinese medicine constituted with Rhizoma Coptidis, RadixScutellariae, CortexPhellodendri amurensis and Fructus Gardeniae, exhibits unambiguous therapeutic effect on cerebral ischemia via multi-targets action. Further investigation, however, is still required to explore the relationship between those mechanisms and targets through system approaches. MATERIALS AND METHODS: Rats of cerebral ischemia were completed by middle cerebral artery occlusion (MCAO) with reperfusion. Following evaluation of pharmacological actions of HLJDD on MCAO rats, the plasma samples from rats of control, MCAO and HLJDD-treated MCAO groups were prepared strictly and subjected to ultra-performance liquid chromatography quadrupole time of flight mass spectrometry for metabolites analysis. The raw mass data were imported to MassLynx software for peak detection and alignment, and further introduced to EZinfo 2.0 software for orthogonal projection to latent structures analysis, principal component analysis and partial least-squares-discriminant analysis. The metabolic pathways assay of those potential biomarkers were performed with MetaboAnalyst through the online database, HMDB, Metlin, KEGG and SMPD. Those intriguing metabolic pathways were further investigated via biochemical assay. RESULTS: HLJDD ameliorated the MCAO-induce cerebral damage and blocked the severe inflammation response. There were nineteen different biomarkers identified among control, MCAO and HLJDD-treated MCAO groups. Ten metabolic pathways were proposed from these significant metabolites. Incorporation with the biochemical assay of cerebral tissue, modulation of metabolic stress, regulation glutamate/GABA-glutamine cycle and enhancement of cholinergic neurons function were explored that involved in the actions of HLJDD on cerebral ischemia. CONCLUSION: HLJDD achieves therapeutic action on cerebral ischemia via coordinating the basic pathophysiological network of metabolic stress, glutamate metabolism, and acetylcholine levels and function.

Statin Use Reduces Prostate Cancer All-Cause Mortality: A Nationwide Population-Based Cohort Study.

Studies have suggested that statin use is related to cancer risk and prostate cancer mortality. We conducted a population-based cohort study to determine whether using statins in prostate cancer patients is associated with reduced all-cause mortality rates. Data were obtained from the Taiwan National Health Insurance Research Database. The study cohort comprised 5179 patients diagnosed with prostate cancer who used statins for at least 6 months between January 1, 1998 and December 31, 2010. To form a comparison group, each patient was randomly frequency-matched (according to age and index date) with a prostate cancer patient who did not use any type of statin-based drugs during the study period. The study endpoint was mortality. The hazard ratio (HR) and 95% confidence interval (CI) were estimated using Cox regression models. Among prostate cancer patients, statin use was associated with significantly decreased all-cause mortality (adjusted HR = 0.65; 95% CI = 0.60-0.71). This phenomenon was observed among various types of statin, age groups, and treatment methods. Analyzing the defined daily dose of statins indicated that both low- and high-dose groups exhibited significantly decreased death rates compared with nonusers, suggesting a dose-response relationship. The results of this population-based cohort study suggest that using statins reduces all-cause mortality among prostate cancer patients, and a dose-response relationship may exist.

Risk of prostate and bladder cancers in patients with spinal cord injury: a population-based cohort study.

OBJECTIVE: To evaluate the risk of prostate and bladder cancers in patients with spinal cord injury (SCI). MATERIALS AND METHODS: We used data obtained from the National Health Insurance system of Taiwan for this study. The SCI cohort contained 54,401 patients with SCI, and each patient was randomly frequency matched with 4 people from the general population (without SCI) based on age, sex, and index date. Incidence rates, SCI cohort to non-SCI cohort rate ratios, and hazard ratios were measured to evaluate the cancer risks. RESULTS: Patients with SCI showed a significantly lower risk of developing prostate cancer compared with subjects without SCI (adjusted hazard ratio = 0.73; 95% confidence interval = 0.59, 0.90), after accounting for the competing risk of death. No significant difference in the risk of bladder cancer emerged between the SCI and control groups. Further analyses found a higher spinal level of SCI tended to predict a lower risk for prostate cancer. CONCLUSIONS: Patients with SCI incurred a lower risk for prostate cancer compared with people without SCI. The risk for bladder cancer did not differ between people with or without SCI.

Higher risk for meningioma in women with uterine myoma: a nationwide population-based retrospective cohort study.

OBJECT: Evidence suggests that hormones play a role in modifying both uterine myoma (UM) and meningioma. A number of studies have observed the positive association between these diseases. The aim of the current population-based study was to determine if women with UM are at a higher risk for meningioma. METHODS: The authors used data from the National Health Insurance system of Taiwan for the study. The UM cohort contained 281,244 women. Each woman was randomly frequency-matched with 4 women without UM, based on age, index year of diagnosis, occupation, urbanization (urbanization level was categorized by the population density of the residential area into 4 levels, with Level 1 as the most urbanized and Level 4 as the least urbanized), and comorbidity, to form the control cohort. Cox's proportional hazard regression analysis was conducted to estimate the influence of UM on the meningioma risk. RESULTS: Among women with UM, the risk of developing meningioma was significantly higher (45%) than among women without UM (95% CI 1.23-1.70). The same phenomenon was observed among most age groups, but a significant difference was only seen in the middle-age range. For women with UM, further analysis did not show a significant change after myomectomy. The cumulative incidence of meningioma between groups with and without UM differed over time. CONCLUSIONS: The nationwide population-based cohort study found that Taiwanese women with UM are at higher risk for developing meningioma.

Cortical reorganization after motor imagery training in chronic stroke patients with severe motor impairment: a longitudinal fMRI study.

INTRODUCTION: Despite its clinical efficacy, few studies have examined the neural mechanisms of motor imagery training (MIT) in stroke. Our objective was to find the cortical reorganization patterns after MIT in chronic stroke patients. METHODS: Twenty stroke patients with severe motor deficits were randomly assigned to the MIT or conventional rehabilitation therapy (CRT) group, but two lost in the follow-up. All 18 patients received CRT 5 days/week for 4 weeks. Nine subjects in the MIT group received 30-min MIT 5 days/week for 4 weeks. Before and after the interventions, the upper limb section of the Fugl-Meyer Scale (FM-UL) was blindly evaluated, and functional magnetic resonance imaging was administered while the patients executed a passive fist clutch task. RESULTS: Two cortical reorganization patterns were found. One pattern consisted of the growth in activation in the contralateral sensorimotor cortex (cSMC) for most patients (six in the MIT group, five in the CRT group), and the other consisted of focusing of the activation in the cSMC with increasing of the laterality index of the SMC for a small portion of patients (three in the MIT group, one in the CRT group). When we applied correlation analyses to the variables of relative ΔcSMC and ΔFM-UL in the 11 patients who experienced the first pattern, a positive relationship was detected. CONCLUSIONS: Our results indicate that different cortical reorganization patterns (increases in or focusing of recruitment to the cSMC region) exist in chronic stroke patients after interventions, and patients may choose efficient patterns to improve their motor function.

Electroacupuncture suppresses discrete cue-evoked heroin-seeking and fos protein expression in the nucleus accumbens core in rats.

Relapse to drug seeking was studied using a rodent model of reinstatement induced by exposure to drug-related cues. Here, we used intravenous drug self-administration procedures in rats to further investigate the beneficial effects of electroacupuncture (EA) on heroin-seeking behavior in a reinstatement model of relapse. We trained Sprague-Dawley rats to nose-poke for i.v. heroin either daily for 4 h or 25 infusions for 14 consecutive days. Then the rats were abstinent from heroin for two weeks. 2 Hz EA stimulation was conducted once daily for 14 days during heroin abstinence. We tested these animals for contextual and discrete cue-induced reinstatement of active responses. We also applied immunohistochemistry to detect Fos-positive nuclei in the nucleus accumbens (NACc) core and shell after reinstatement test. We found that active responses elicited by both contextual cues and discrete cues were high in the rats trained with heroin than in saline controls. EA treatment significantly reduced active responses elicited by discrete cues. EA stimulation attenuated Fos expression in the core but not the shell of the NACc. Altogether, these results highlight the therapeutic benefit of EA in preventing relapse to drug addiction.

Column bioleaching of uranium embedded in granite porphyry by a mesophilic acidophilic consortium.

A mesophilic acidophilic consortium was enriched from acid mine drainage samples collected from several uranium mines in China. The performance of the consortium in column bioleaching of low-grade uranium embedded in granite porphyry was investigated. The influences of several chemical parameters on uranium extraction in column reactor were also investigated. A uranium recovery of 96.82% was achieved in 97 days column leaching process including 33 days acid pre-leaching stage and 64 days bioleaching stage. It was reflected that indirect leaching mechanism took precedence over direct. Furthermore, the bacterial community structure was analyzed by using Amplified Ribosomal DNA Restriction Analysis. The results showed that microorganisms on the residual surface were more diverse than that in the solution. Acidithiobacillus ferrooxidans was the dominant species in the solution and Leptospirillum ferriphilum on the residual surface.

New anti-HBV caryophyllane-type sesquiterpenoids from Euphorbia humifusa Willd.

Activity-guided fractionation of Euphorbia humifusa for anti-HBV activity led to the isolation of two novel sesquiterpenoids, named humifusane A (1) and humifusane B (2). Their structures were elucidated by spectral data to show that they have a caryophyllane-type precursor structure. The two new sesquiterpenoids showed anti-HBV activities through specifically inhibiting the secretion of HBsAg in HepG2.2.15.

Anti-HBV active flavone glucosides from Euphorbia humifusa Willd.

Thirteen flavone glucosides from the herb of Euphorbia humifusa were isolated and elucidated. Among them, five compounds including apigenin-7-O-ß-D-glucopyranoside (2), apigenin-7-O-(6''-O-galloyl)-ß-D-glucopyranoside (3), luteolin-7-O-ß-D-glucopyranoside (7), luteolin-7-O-(6''-O-trans-feruloyl)-ß-D-glucopyranoside (8) and luteolin-7-O-(6''-O-coumaroyl)-ß-D-glucopyranoside (9) showed anti-HBV activity in vitro. The structure-activity relationship showed that the parent structure was closely relevant to the anti-HBV activity of these compounds (agigenin>luteolin>quercetin). It was found that the number of glucoside in the structure may significantly influence their activities (flavone monoglucoside>flavone diglucoside) and cytotoxicity (flavone>flavone monoglucoside>flavone diglucoside). In addition, the substitution of acyl group on glucoside may be important to keep the anti-HBV activities of these compounds (galloyl>feruloyl>coumaroyl).

[Phenols from Euphorbia humifusa].

The investigation on the herbal of Euphorbia humifusa Wild. was carried out to find its anti-HBV constituents. The isolation and purification were performed by chromatography such as macroporous resin, polyamide, Sephadex LH-20, MCI GEL CHP 20P and so on. Based on the spectral analysis, seven phenols were identified as brevifolin (1), brevifolin carboxylic acid (2), methyl brevifolincarboxylate (3), phyllanthussin E methyl ester (4), sanguisorbic acid dilactone (5), 3,3'-2-di-O-methyl ellagic acid (6), ellagic acid (7). Among them, Compounds 2-6 were isolated from this plant for the first time.

Strength and fluoride release characteristics of a calcium fluoride based dental nanocomposite.

Secondary caries and restoration fracture remain the two most common problems in restorative dentistry. Release of fluoride ions (F) could be a substantial benefit because F could enrich neighboring enamel or dentin to combat caries. The objective of this study was to incorporate novel CaF(2) nanoparticles into dental resin to develop stress-bearing, F-releasing nanocomposite. CaF(2) nanoparticles, prepared in our laboratories for the first time, were combined with reinforcing whisker fillers in a resin. Flexural strength (mean+/-sd; n=6) was 110+/-11 MPa for the composite containing 30% CaF(2) and 35% whiskers by mass. It matched the 108+/-19 MPa of a stress-bearing, non-releasing commercial composite (Tukey's at 0.05). The composite containing 20% CaF(2) had a cumulative F release of 2.34+/-0.26 mmol/L at 10 weeks. The initial F release rate was 2 microg/(hcm(2)), and the sustained release rate after 10 weeks was 0.29 microg/(hcm(2)). These values exceeded the reported releases of traditional and resin-modified glass ionomer materials. In summary, nanocomposites were developed with relatively high strength as well as sustained release of fluoride ions, a combination not available in current materials. These strong and F-releasing composites may yield restorations that can reduce the occurrence of both secondary caries and restoration fracture.

[Optimization of preparative separation and purification of water-soluble substance from Salvia miltiorrhiza by macroporous resins].

OBJECTIVE: To study the optimum conditions for the isolation and purification of water-soluble substance from Salvia miltiorrhiza Bge. METHODS: The optimum macroporous resin was selected and the separation and purification process was evaluated by measuring the content of Salvianolic acid B in the fractions by HPLC. RESULTS: The XDA-5 macroporous resin was the most effective compared with other macroporous resins. The optimum conditions were screened, which were 18 mg/ml corresponding to Salvianolic acid B for concentration of extract, pH was 4, and the volume of 70% (V/V) ethanol as eluant was 3 BV. By this method, the elution efficiency of Salvianolic acid B exceeded 90%. CONCLUSION: The method is more effective for large-scale isolation and purification of water-soluble substance from Salvia miltiorrhiza Bge.

[Effects of electroacupuncture of low frequency on heroin-seeking behavior and FosB protein expression in relative brain regions].

OBJECTIVE: To observe effects of electroacupuncture (EA) of low frequency on heroin-seeking behavior and FosB protein expression in relative brain regions so as to explore the mechanism of EA. METHODS: Rat model of relapsing into heroin was established with progressive fixed ratio program, and model rats were randomly divided into 3 groups: a "Sanyinjiao" needle-retention control group, a low frequency and weak EA group, and a low frequency and strong EA group. Heroin-seeking behavior was elicited by conditional clue and small dose of heroin; FosB protein expression was investigated with immunohistochemical technique. RESULTS: After treatment, the heroin-seeking behavior induced by conditional clue decreased in the needle-retention control group and the weak EA group, and the heroin-seeking behavior induced by small dose of heroin in the weak EA group significantly reduced as compared with the control group, and FosB protein expression in the nucleus accumbens septi, globus pallidus, basolateral amygdaloid nucleus significantly decreased in the weak EA group, and did not significantly change in the strong EA group; the activity induced by heroin increased as compared with those in the control group and the weak EA group. CONCLUSION: EA of low frequency and low intensity can cure the heroin-seeking behavior, which is correlated with regulating nervous adaptation of nucleus accumbens septi, basolateral amygdaloid nucleus, etc..