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Spinal cord injury (SCI) is a very serious clinical traumatic illness with a very high disability rate. It not only causes serious functional disorders below the injured segment, but also causes unimaginable economic burden to social development. Exosomes are nano-sized cellular communication carriers that exist stably in almost all organisms and cell types. Because of their capacity to transport proteins, lipids, and nucleic acids, they affect various physiological and pathological functions of recipient cells and parental cells. Autophagy is a process that relies on the lysosomal pathway to degrade cytoplasmic proteins and organelles and involves a variety of pathophysiological processes. Exosomes and autophagy play critical roles in cellular homeostasis following spinal cord injury. Presently, the coordination mechanism of exosomes and autophagy has attracted much attention in the early efficacy of spinal cord injury. In this review, we discussed the interaction of autophagy and exosomes from the perspective of molecular mechanisms, which might provide novel insights for the early therapeutic application of spinal cord injury.

Objective. The aim of this study was to summarize and evaluate the efficacy of acupuncture in hypertension animal study. Methods. Studies were searched from six databases, including Medline, Embase, Chinese National Knowledge Infrastructure, Wanfang Data, VIP information database, and Chinese Biomedical Literature Database. Study quality of each included study was evaluated according to the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines, and the risk of bias was evaluated by the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were selected as outcomes. Meta-analyses were performed using Stata 12.0 software. The effect size was calculated by combining SBP/DBP/MAP data with the random effects model, respectively. Results. 67 studies containing 1522 animals were included. According to the ARRIVE guideline, 8 items were assessed as poor and 4 items were assessed as excellent. According to the SYRCLE tool, all studies were judged as having high risk of bias. Compared with the hypertension group, the pooled results showed significant antihypertension effects of acupuncture for SBP, DBP, and MAP. Similarly, compared with the sham-acupuncture group, the pooled results showed significant antihypertension effects of acupuncture for SBP, DBP, and MAP. Conclusion. Although pooled data suggested that the acupuncture group was superior to the hypertension group or sham-acupuncture group for SBP/DBP/MAP, the presentation of poor methodological quality, high risk of bias, and heterogeneity deserves cautious interpretation of the results.

To evaluate the clinical efficacy of acupuncture at different timings in acute stage for limb dysfunction in patients with cerebral infarction.A total of 101 patients with cerebral infarction limb dysfunction were divided into an early exposure group (Compared before treatment, the mRS grade at 30 and 60 days after onset in the early exposure group was improved (The timing of acupuncture is an independent factor affecting the disability status and limb motor dysfunction in patients with cerebral infarction, and the effect of early intervention may be better than late intervention.

This study aimed to evaluate the efficacy and adherence of sublingual immunotherapy (SLIT) for house dust mite (HDM)-induced allergic rhinitis (AR) patients over 60 years old.Eighty-six AR patients aged 60-75 years old were randomly divided in the control and treatment group as 1:1 ratio. The control group was treated with standard pharmacotherapy while the treatment group was treated with SLIT plus pharmacotherapy on demand. Patients adherence, combined symptom and medication score (CSMS), visual analog scale (VAS), and presence of adverse events were evaluated in the baseline and after 6-months, 12-months and 24-months treatment.Twenty-five (58.1%) subjects in the treatment group and 20 (46.5%) subjects in the control group completed the study (P 0.05). The major reasons for premature cessation were out of touch and relieved symptoms. At the same time, CSMS and VAS of the patients over 60 years old in both groups significantly decreased from baseline to any post-baseline time point (all P 0.05). The comparison of CSMS and VAS between the two groups revealed statistically significant differences in favor of the SLIT group at month 24 (P 0.05), whereas no differences at month 6 and month 12 (all P 0.05).41.9% of the patients dropped out within 2 years of SLIT treatment and the major reasons for premature cessation were out of touch and relieved symptoms. This study suggested that SLIT plus pharmacotherapy provided a greater clinical benefit than pharmacotherapy alone at two years.

The main constituents of a typical medicinal herb, Polygonum multiflorum (Heshouwu in Chinese), that induces idiosyncratic liver injury remain unclear. Our previous work has shown that cotreatment with a nontoxic dose of lipopolysaccharide (LPS) and therapeutic dose of Heshouwu can induce liver injury in rats, whereas the solo treatment cannot induce observable injury. In the present work, using the constituent "knock-out" and "knock-in" strategy, we found that the ethyl acetate (EA) extract of Heshouwu displayed comparable idiosyncratic hepatotoxicity to the whole extract in LPS-treated rats. Results indicated a significant elevation of plasma alanine aminotransferase, aspartate aminotransferase, and liver histologic changes, whereas other separated fractions failed to induce liver injury. The mixture of EA extract with other separated fractions induced comparable idiosyncratic hepatotoxicity to the whole extract in LPS-treated rats. Chemical analysis further revealed that 2,3,5,4'-tetrahydroxy trans-stilbene-2-O-β-glucoside (trans-SG) and its cis-isomer were the two major compounds in EA extract. Furthermore, the isolated cis-, and not its trans-isomer, displayed comparable idiosyncratic hepatotoxicity to EA extract in LPS-treated rats. Higher contents of cis-SG were detected in Heshouwu liquor or preparations from actual liver intoxication patients associated with Heshouwu compared with general collected samples. In addition, plasma metabolomics analysis showed that cis-SG-disturbing enriched pathways remarkably differed from trans-SG ones in LPS-treated rats. All these results suggested that cis-SG was closely associated with the idiosyncratic hepatotoxicity of Heshouwu. Considering that the cis-trans isomerization of trans-SG was mediated by ultraviolet light or sunlight, our findings serve as reference for controlling photoisomerization in drug discovery and for the clinical use of Heshouwu and stilbene-related medications.

Aconite is a valuable drug and also a toxic material, which can be used only after detoxification processing. Although traditional processing methods can achieve detoxification effect as desired, there are some obvious drawbacks, including a significant loss of alkaloids and poor quality consistency. It is thus necessary to develop a new detoxification approach. In the present study, we designed a novel one-step detoxification approach by quickly drying fresh-cut aconite particles. In order to evaluate the technical advantages, the contents of mesaconitine, aconitine, hypaconitine, benzoylmesaconine, benzoylaconine, benzoylhypaconine, neoline, fuziline, songorine, and talatisamine were determined using HPLC and UHPLC/Q-TOF-MS. Multivariate analysis methods, such as Clustering analysis and Principle component analysis, were applied to determine the quality differences between samples. Our results showed that traditional processes could reduce toxicity as desired, but also led to more than 85.2% alkaloids loss. However, our novel one-step method was capable of achieving virtually the same detoxification effect, with only an approximately 30% alkaloids loss. Cluster analysis and Principal component analysis analyses suggested that Shengfupian and the novel products were significantly different from various traditional products. Acute toxicity testing showed that the novel products achieved a good detoxification effect, with its maximum tolerated dose being equivalent to 20 times of adult dosage. And cardiac effect testing also showed that the activity of the novel products was stronger than that of traditional products. Moreover, particles specification greatly improved the quality consistency of the novel products, which was immensely superior to the traditional products. These results would help guide the rational optimization of aconite processing technologies, providing better drugs for clinical treatment.

Ethnopharmacological relevance Polygonum multiflorum L. is a famous traditional Chinese medicine that has always been perceived to be safe. Recently, the increasing case reports on hepatotoxicity induced by Raw P. multiflorum (RP) have attracted particular attention. However, the diagnosis and identification of RP-induced hepatotoxicity are still very difficult for its unknown mechanism and the lack of specific biomarkers. Aim of the study To further explore the toxicity and metabolic mechanisms involved in the hepatotoxicity induced by RP. Materials and methods The hepatotoxicity induced by RP and its processed products (PP) (dosed at 20 g/kg for 4 weeks) on rats were investigated using conventional approaches including the biochemical analysis and histopathological observations. Further, a urinary metabolomic approach was developed to study the metabolic disturbances caused by RP and PP, followed by the pattern recognition approach and pathways analysis. Results RP showed obvious hepatotoxity whereas PP did not. 16 potential biomarkers (pyridoxamine, 4-pyridoxic acid, citrate et al.) differentially expressed in RP group were identified compared with the control and PP-treated groups. The pathways analysis showed that vitamin B6 metabolism, tryptophan metabolism and citrate cycle might be the major enriched pathways involved in the hepatotoxicity of the herb. Conclusion 16 differentially expressed metabolites were identified to be involved in the RP-induced hepatotoxicity. Vitamin B6 metabolism might be mostly related to the hepatotoxicity induced by RP. This finding may provide a potential therapeutic target or option to treat hepatotoxicity induced by RP.

The root of Polygonum multiflorum Thunb (PM) has been used in China to treat a variety of diseases, such as constipation, early graying of the hair and hyperlipemia. Recent evidence shows that PM causes idiosyncratic drug-induced liver injury (IDILI) in humans. In this study, we investigated the molecular basis of PM-induced liver injury in a rat model of IDILI based on a non-hepatotoxic dose of LPS. SD rats were orally administered 3 potentially hepatotoxic compounds of PM: cis-stilbene glucoside (cis-SG, 50 mg/kg), trans-SG (50 mg/kg) or emodin (5 mg/kg), followed by injection of LPS (2.8 mg/kg, iv). Serum and liver histology were evaluated 7 h after LPS injection. Among the 3 compounds tested, cis-SG, but not emodin or trans-SG, induced severe liver injury in rats when combined with LPS. The levels of AST and ALT in plasma and inflammatory cytokines in both plasma and liver tissues were markedly elevated. The liver tissues showed increased injury, hepatocyte apoptosis, and macrophage infiltration, and decreased cell proliferation. Microarray analysis revealed a negative correlation between peroxisome proliferator-activated receptor-γ (PPAR-γ) and LPS/cis-SG-induced liver injury. Immunohistochemical staining and RT-PCR results further confirmed that cis-SG significantly inhibited activation of the PPAR-γ pathway in the liver tissues of LPS/cis-SG-treated rats. Pre-treatment with a PPAR-γ agonist pioglitazone (500 g/kg, ig) reversed LPS/cis-SG-induced liver injury, which was associated with inhibiting the nuclear factor kappa B (NF-κB) pathway. These data demonstrate that cis-stilbene glucoside induces immunological idiosyncratic hepatotoxicity through suppressing PPAR-γ in a rat model of IDILI.

Objective: Discusses the application of multi-media technology in the hematology test teaching. Methods: Based on characteristics of hematology test subject, this article analyzes advantages and existing problems in the multi-media technology in teaching. Results: Multi-media teaching as a modern teaching means, compared with the clinical hematology test of traditional teaching mode has more obvious advantages. Conclusion: Multi-media technology applied in hematology test teaching, giving people the traditional teaching mode of new energy, optimized the teaching content, improve teaching efficiency and quality.

To cope with the challenges of climate change, Chinese transportation industry has been working to promote green transportation development. Brazil and China are both developing countries and also the "BRIC Countries". Considering their energy strategies and energy advantages, Brazil and China have made beneficial attempts in transport energy-saving emission reduction and achieved success. The experience of Brazil transportation energy conservation and emission reduction will provide positive and beneficial reference for promoting green recycling and low carbon transport construction in China.

Decoction is one of the most commonly used dosage forms of traditional Chinese medicine. The stability of chemical constituents in decoction is closely related to the clinical efficacy and safety. There were few reports about the influence of metal ions in the stability of chemical constituents in traditional Chinese medicine. However, there is no evidence that metal ions in decoction water need to be controlled. In this study, 2,3,5,4'-tetrahydroxy stilbene-2-O-β-D-glucoside (THSG), one of the main constituents in Polygoni Multiflori Radix was studied. Ordinary tap water, deionized water, and water containing different metal ions were used to investigate and compare the influence on THSG. The results showed that after storage in a dark place at the room temperature for 10 days, the degradation of THSG was 7% in deionized water, while undetectable in tap water. The content of THSG could be decreased by different kinds of metal ions, and the effect was concentration-dependent. Moreover, Fe3+ and Fe2+ showed the greatest influence at the same concentration; and our study has shown that THSG decreased more than 98% in Fe and Fe2+ solutions at 500 ppm concentration. In the same time we found out p-hydroxybenzaldehyde (molecular weight: 122.036 7) and 2,3,5-trihydroxybenzaldehyde-2-O-glycoside (molecular weight: 316.079 4) were the main degradation products of THSG in tap water and water containing Cu2+, Ca2+, Zn2+, Mg2+ and Al3+. The product of THSG dimer with a water molecule was found in water containing Fe3+ and Fe2+. The above results showed that the metal ions in water could significantly influence the stability of THSG in water, indicating that the clinical efficacy and safety of decoction would be affected if the metal ions in water were not under control. It's suggested that deionized water should be used in the preparation of decoction containing Polygoni Multiflori Radix in the clinic to avoid degradation of THSG. Meanwhile, decoction prepared by tap water should be taken by patients in a short time. Our investigation provides important information and reference about the influence of metal ions on the stability of decoctions in other traditional Chinese medicine that have unstable groups such as hydroxyls and unsaturated bonds, etc.

Many foods and herbs are experientially classified into different commodity grades in commercial circulation. Regarding the hypertoxic herb aconite, large samples are considered to be of better quality. However, this experiential classification lacks a scientific basis. In this study, we focused on the quality diversity among different grades and studied it using the minimum lethal dose assay and a novel ultra high performance liquid chromatography coupled with time-of-flight mass spectrometry method. Toxicity assay result suggested grade I aconite had the lowest toxicity (p < 0.05). Using this method with partial least squares-discriminant analysis, we discovered nine chemomarkers, including neoline, songorine, fuziline, mesaconitine, talatizidine, dexyaconitine, talatisamine, hypaconitine, and fuzitine. Considering their toxicity and activity, we found the levels of toxic ingredients hypaconitine, dexyaconitine, and mesaconitine in grade I were lower than those in grade II (p < 0.01), while the levels of efficacy ingredients songorine, talatisamine, and neoline were the highest in grade I (p < 0.01). Further study demonstrated that the quality variation was associated with plant tissue development and toxic ingredient distribution law. Our results provide scientific evidence for the experiential quality evaluation of aconite, and it will be of great utility for other foods and herbs.

Impressed by the exceptional anticancer activity of cinnamon, the present study was conducted to elucidate the anticancer potential of essential oil of Cinnamon (EOC).EOC was tested against various cell lines (FaDu, Detroit-562 and SCC-25) of head and neck squamous cell carcinoma (HNSCC) using MTT assay. The Hep-2 cell xenograft model was used to assess the positive bio-activity of EOC. EGFR-TK inhibitory assay was also carried out to explain the possible mechanism of action of EOC. Moreover, to rationalise the key contacts responsible for attenuating EGFR, the major component of EOC, i.e., trans-cinnamaldehyde, as identified by GC-MS analysis, was subjected to molecular docking experiments with the catalytic domain of EGFR protein model.EOC exhibited significant anticancer activity with percent inhibition 66.12, 87.32, and 99.34%, against FaDu, Detroit-562 and SCC-25, respectively. Moreover, EOC reduced the tumor burden to 43.5% in Hep-2 cell xenograft model along with 89% inhibition of EGFR-TK activity in the EGFR-TK inhibitory assay. Docking experiments showed that trans-cinnamaldehyde was proficiently fitted into the inner grove of the active site of EGFR by making close inter-atomic contacts with the key catalytic residues Val702, Ala719, Lys721, Leu764, Thr766 and Leu820 and with inhibition constant Ki = 775.93 μM.EOC exhibits significant anticancer activity against HNSCC cells in vitro. The mechanism underlying its anticancer action was attributed to the suppression of EGFR-TK. It also significantly suppressed the tumor growth in Hep-2 cell xenograft model.

Purpose: To demonstrate the role of chloroquinone (CQ) in inducing apoptosis in HONE-1 and HNE-1, nasopharyngeal carcinoma (NPC) cell lines. Methods: Water-soluble tetrazolium salt (WST)-1 assay was used for the determination of cell proliferation while an inverted microscope was employed for the analysis of alterations in the morphology of the cells. Results: CQ treatment led to a significant reduction in the rate of cell proliferation in NPC cells after 48 h. In HONE-1 and HNE-1 cell lines viability was reduced to 89 and 82 %, respectively on treatment with 10 μΜ concentration of CQ without affecting normal human skin keratinocyte cell line, K38. The expression of Ki67, a marker for proliferation as well as proliferating cell nuclear antigen (PCNA), decreased in the CQ-treated NPC cells. Morphological examination of NPC cells revealed cell apoptosis on treatment with CQ after 48 h. Treatment of NPC cells with CQ induced activation of caspases and DNA was damaged which further confirmed CQ mediated induction of apoptosis. The level of apoptotic cells in CQ treated and untreated control HONE-1 cell cultures was 53.67 and 3.78 %, respectively (p

We put forward a new specialty blasting method to solve drill-jamming based on stress concentration and stress wave theory. Drill-jamming accident of banji was successfully solved at the early 2006 through this method first: for this drill-jamming, study drilling tools and location of drill-jamming to find the weak position (Fig. 1); produce impact loading and form stress concentration (Fig. 3) at weak position by place well-designed explosive package at special position. Through many times controllable safe explosions and repeatedly impact loading, accurate fracture, separate sinker bar and the above parts from drill bit, this part raised up successfully (Fig. 7). The rest would be taken out after second reaming.

According to different toxicities of various aqueous extracts of Polygonum multiflorum on hepatocyte, the impacts of chemical composition on the safety of P. multiforum was studied. In this study, 8 main chemical compositions in aqueous extracts of P. multiflorum were determined by the established HPLC method; at the same time, the inhibition ratios of different aqueous extracts of P. multiflorum on L02 cell were determined. Afterwards, the potential compounds related to the toxicity of P. multiforum were tentatively found through a multiple correlation analysis. The results showed that P. multiforum with different chemical compositions exhibited great differences in dissolution. The hepatocyte toxicity of P. multiflorum powder was much greater than P. multiflorum lumps. In addition, three constituents closely related to toxicity of P. multiflorum were found by multiple correlation analysis. The study revealed that chemical composition of P. multiflorum is closely related to the hepatotoxicity, and the hepatotoxicity of P. multiflorum powder is greater than that of other dosage forms. This study indicates that P. multiflorum with different chemical compositions show varying toxicity, which therefore shall be given high attention.

Xiao Ma,1,2 Yan-ling Zhao,2 Yun Zhu,3 Zhe Chen,1,2 Jia-bo Wang,4 Rui-yu Li,1,4 Chang Chen,1,2 Shi-zhang Wei,1,2 Jian-yu Li,3 Bing Liu,5 Rui-lin Wang,3 Yong-gang Li,3 Li-fu Wang,3 Xiao-he Xiao4 1Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Department of Pharmacy, 302 Military Hospital of People’s Liberation Army, Beijing, People’s Republic of China; 3Department of Integrative Medical Center, 302 Military Hospital of People’s Liberation Army, Beijing, People’s Republic of China; 4China Military Institute of Chinese Medicine, 302 Military Hospital of People’s Liberation Army, Beijing, People’s Republic of China; 5School of Chinese Medicine, The University of Hong Kong, Hong Kong Background: Paeonia lactiflora Pall. (PLP), a traditional Chinese herbal medicine, has been used for hepatic disease treatment over thousands of years. In our previous study, PLP was shown to demonstrate therapeutic effect on hepatitis with severe cholestasis. The aim of this study was to evaluate the antioxidative effect of PLP on alpha-naphthylisothiocyanate (ANIT)-induced cholestasis by activating NF-E2-related factor 2 (Nrf2) via phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Materials and methods: Liquid chromatography-mass spectrometry (LC-MS) was performed to identify the main compounds present in PLP. The mechanism of action of PLP and its therapeutic effect on cholestasis, induced by ANIT, were further investigated. Serum indices such as total bilirubin (TBIL), direct bilirubin (DBIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GT), and total bile acid (TBA) were measured, and histopathology of liver was also performed to determine the efficacy of treatment with PLP. Moreover, in order to illustrate the underlying signaling pathway, liver glutathione (GSH) content and mRNA or protein levels of glutamate-cysteine ligase catalytic subunit (GCLc), glutamate-cysteine ligase modulatory subunit (GCLm), Akt, heme oxygenase-1 (HO-1), NAD(P)H/quinone oxidoreductase 1 (Nqo1), and Nrf2 were further analyzed. In addition, validation of PLP putative target network was also performed in silico. Results: Four major compounds including paeoniflorin, albiflorin, oxypaeoniflorin, and benzoylpaeoniflorin were identified by LC-MS analysis in water extract of PLP. Moreover, PLP could remarkably downregulate serum levels of TBIL, DBIL, AST, ALT, ALP, γ-GT, and TBA, and alleviate the histological damage of liver tissue caused by ANIT. It enhanced antioxidative system by activating PI3K/Akt/Nrf2 pathway through increasing Akt, Nrf2, HO-1, Nqo1, GCLc, and GCLm expression. The putative targets network validation also confirmed the important role of PLP in activating Akt expression. Conclusion: The potential mechanism of PLP in alleviating ANIT-induced cholestasis could to be related to the induction of GSH synthesis by activating Nrf2 through PI3K/Akt-dependent pathway. This indicates that PLP might be a potential therapeutic agent for cholestasis. Keywords: Paeonia lactiflora Pall., cholestatic hepatitis, antioxidation, Nrf2, Akt

As a representative variety of hypertoxic herbs, aconite has a very high medicinal value but certain security risks. With the advance of urbanization and industrial transfer and upgrading, traditional geo-authentic regions and emerging regions have gradually coexisted. However, there are significant differences in the geographical distribution, ecological environment and growing cycle in these areas, which may cause intraspecific variations in chemical components, and then affect herb quality and clinical efficacy. Furthermore, there was still lack of in-depth study on characteristic constituents of aconite genuineness. In this paper, an UPLC-Q-TOF-MS was used to investigate the chemical ingredients in Jiangyou aconite, Hanzhong aconite, Butuo aconite and Weishan aconite. The results suggested that using unsupervised PCA method, Jiangyou aconite was similar with Hanzhong aconite in chemical ingredients, but significantly different from ones in emerging regions. Using PLS-DA method, seven characteristic constituents were identified, in which Butuo aconite and Weishan aconite had higher contents of mesaconitine and fuziline, while Jiangyou aconite and Hanzhong aconite had higher contents of hypaconitine, neoline, carmichaeline, and songorine. Based on basic toxicity of each ingredient, we can find that hypaconitine and mesaconitine were the key toxicity factors to distinguish Jiangyou aconite, Butuo aconite, and Weishan aconite. The toxicity of geo-authentic Jiangyou aconite was lower than that of Butuo aconite and Weishan aconite. The lower toxicity in geo-authentic Jiangyou aconite was beneficial for ensuring clinical drug safety, which may be one of the important reasons for the formation of genuine aconite. These results provide new reference data to reveal the formation mechanism of genuine aconite from the perspective of plant secondary metabolite diversity.

Maternally inherited diabetes and deafness (MIDD), a mitochondrial disease first described in 1992, results from the mitochondrial DNA mutation and affects up to 1% of the patients with diabetes. This review discusses the biomedical mechanisms of MIDD patients; summarizes the recent improvement of clinical and genetic diagnosis of MIDD; outlines the advances of the clinical management of these patients and their families.