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To review the efforts and progress in promoting quality and transparency of health research in China and to discuss how to improve.We focused on three different types of health research: clinical trials, systematic reviews, and clinical practice guidelines, and summarized China's progress from their registration, implementation, and reporting stages.In the last 3 decades, China's major works include the following: 1) For registration, the trials and CPGs registries have been set up, and released policies to mandate registration and submission of protocols for trials. 2) For implementation, multiple clinical research and EBM centers have been established. The ResMan platform for data management has been created and required researchers to share results data. 3) For reporting, the Chinese EQUATOR Center has been set up. Translations and extensions of the CONSORT, PRISMA, and RIGHT have been published. 4) For traditional Chinese medicine (TCM), specific guidelines for the registration and reporting of TCM research have been developed.China has made progress in promoting research quality and transparency, especially in research registration and reporting. Nevertheless, more can be done in data management and sharing for research implementation, and good publication practices in TCM.

To assess the reporting quality of randomized controlled trials (RCTs) with multicenter design, particularly whether necessary information related to multicenter characteristics was adequately reported.Through a search of 4 international electronic databases, we identified multicenter RCTs published in English from 1975 to 2019. Reporting quality was assessed by the CONSORT (Consolidated Standards of Reporting Trials) checklist (37 items) and by a self-designed multicenter-specific checklist (27 items covering multicenter design, implement and analysis). The scores of trials published in three time periods (1975-1995; 1996-2009; and 2010-2019) were also compared.A total of 2,844 multicenter RCTs were included. For the CONSORT checklist, the mean (standard deviation) reporting score was 24.1 (5.5), 12 items were assessed as excellent (90%), 12 items as good (50%-90%), and 13 items as poor (50%). For the multicenter checklist, the reporting score was 3.9 (2.2), only 3 items were excellent or good, and the remaining 24 items were poor. Time period comparison showed that reporting quality improved over time, especially after the CONSORT 2010 issued.Although CONSORT appears to have enhanced the reporting quality of multicenter RCTs, further improvement is needed. A "CONSORT extension for multicenter trials" should be developed.

Spexin (SPX) acts as a neuropeptide with pleiotropic functions that can participate in anxiety regulation. Corticotropin releasing factor (CRF) is widely expressed in brain tissues and associated with depression and anxiety and addiction. With the anxious mice under chronic unpredictable stress, we found SPX mRNA expression level in the hippocampus of the brain was significantly reduced, while local CRF mRNA expression level was increased. Furthermore, CRF injection in the hippocampus could also decrease SPX mRNA expression levels in hippocampus and other brain tissues, including pituitary and hypothalamus. With the primary mouse hippocampal cell model, CRF treatment could decrease SPX mRNA expression at hippocampal cell level and this inhibitory effect was mediated only by corticotropin releasing factor receptor 2 (CRFR2) but not corticotropin releasing factor receptor 1 (CRFR1). In HEK293 cells with CRFR2 over-expression, CRF could also inhibit SPX promoter activity coupling with AC/cAMP/PKA and MEK1/2/Erk1/2 cascades. In addition, Epac was also involved with the CRF-repressed SPX promoter activity and cross-talked with MEK1/2/Erk1/2 pathway. CRF could inhibit SPX gene expression in mouse hippocampus via transcriptional activation at the promoter level with coupling of AC/cAMP and MEK1/2/Erk1/2 signaling, which will be relevant to the anxiety response mediated by SPX in central nervous system.

Stroke is the second leading cause of death worldwide. In Hong Kong, the proportion of deaths caused by cerebrovascular disease accounted for approximately 6.8% of total deaths. Although integrative medicine approaches are widely adapted by patients, there is a lack of guideline to support the corresponding clinical practice for stroke management and rehabilitation. Therefore, we design this framework for the development of an integrative medicine clinical practice guideline (CPG) for stroke.The framework follows the instructions of World Health Organization (WHO) handbook for guideline development, Guideline International Network (GIN), Appraisal of Guidelines for Research and Evaluation Instrument (AGREE II), and Reporting Items for Practice Guidelines in Healthcare (RIGHT). Three stages with ten steps are conducted.Clinical practice guidelines are essential to provide optimal recommendations for patients' prognosis. With proper methodology, this framework will facilitate the formation of clinical practice guideline for stroke through synthesizing evidences in the scope of integrative medicine.

Currently, there is no effective treatment for Burkitt's lymphoma in patients aged above 60 years, and thus research on effective treatment options for Burkitt's lymphoma has been gaining increasing attention. Artesunate has been identified as a novel effective growth suppressor in Burkitt's lymphoma. Here, we utilized molecular biology, transcriptome analysis, and other techniques to study artesunate-induced death of the Burkitt's lymphoma cells DAUDI and CA-46, the effect of artesunate on gene expression in DAUDI and CA-46 cells, and the effect of artesunate-induced ATF4-CHOP-CHAC1 pathway on ferroptosis. We also studied the inhibitory effects and ferroptosis induction of artesunate on CA-46 cells in mouse xenografts. Results showed that artesunate induced ferroptosis in DAUDI and CA-46 cells, as evidenced by the protective effect of liproxstatin-1, ferrostatin-1, and desferoxamine, resulting in an endoplasmic reticulum stress response, a ctivation of the ATF4-CHOP-CHAC1 pathway enhanced ferroptosis in DAUDI and CA-46 cells. A mouse-transplanted tumor model showed that artesunate can inhibit the proliferation and induce ferroptosis of CA-46 cells in vivo. This study provides a novel perspective for the development of drugs against different types of Burkitt's lymphomas.

Gut barrier makes a huge research gap between in vivo and in vitro studies of orally bioactive polysaccharides: whether/how they contact the related cells in vivo. A hyperbranched heteroglycan RAP from Radix Astragali, exerting antitumor and immunomodulatory effects in vitro and in vivo, is right an example. Here, we determined first that RAP's antitumor activity is immune-dependent. Being undegraded and non-absorbing, RAP quickly entered Peyer's patches (PPs) in 1 h where it directly targeted follicle dendritic cells and initiated antitumor immune responses. RAP was further delivered to mesenteric lymph node, bone marrow, and tumor. By contrast, the control Dendrobium officinale polysaccharide did not enter PPs. These findings revealed a blood/microbiota-independent and selective lymphatic route for orally administrated RAP to directly contact immune cells and trigger antitumor immune responses. This route bridges the research gap between the in vitro and in vivo studies and might apply to many other bioactive polysaccharides.

Background: Lipopolysaccharide(LPS) inserts into the hydrophobic binding pocket of the myeloid differentiation protein 2(MD-2) that bound to toll-like receptor 4(TLR4). TLR4 antagonists have been designed based on the structure of lipid A, the innermost regions of LPS. However, these antagonists have poor bioavailability and may be toxic. Furthermore, the presence of lipid A moiety is not necessary for driving TLR4 activation. Therefore, compound directly binds to TLR4 is a better strategy to inhibit TLR4 activity. Methods: Biophysical techniques were used to examine the direct binding between baicalein and TLR4. With colorectal cancer(CRC) as models, coupled with drug-target-disease network, protein-protein interaction network and functional studies, the effect and the associated underlying mechanism of action upon the binding baicalein to TLR4 were examined. Findings: We evidently show a direct physical binding of baicalein to TLR4 in molecular docking, surface plasmon resonance biosensor analysis and bio-layer interferometry analysis. With CRC cells as model, we demonstrate the binding of baicalein to TLR4 with cellular thermal shift assay; which interrupts the binding of LPS to TLR4-MD-2 in the cells. Baicalein inhibits TLR4 activity, reduces CRC cell viability and migration in TLR4-dependent manner. Drug–targets–disease network and protein-protein interaction network highlight hypoxia inducible factor(HIF-1α) and vascular endothelial growth factor(VEGF) as downstream of TLR4, which are further validated in cell models. Involvement of TLR4/HIF-1α/VEGF axis in the anti-CRC and anti-angiogenic effect of baicalein is demonstrated in CRC-bearing mice and chick-chorioallantoic-membrane assay, respectively. Our study provides evidence to support the translation of baicalein into TLR4-targeting therapeutics. Funding Information: This work was partially supported by Research Grant Council of HKSAR HKBU-22103017-ECS, Innovation & Technology Commission #PRP/015/19FX, National Natural Science Foundation of China #SCM-2016-NSFC-003 and Natural Science Foundation of Guangdong Province #2018A0303130122 to HYK; the National Natural Science Foundation of China (82074019 and 81703705), Characteristic innovation projects of universities in Guangdong Province (2020KTSCX030), the Opening Project of Zhejiang Provincial Preponderant and Characteristic Subject of Key University (Traditional Chinese Pharmacology), Zhejiang Chinese Medical University (ZYAOX2018010) to ST. Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: Animal experiments were approved by the Guangzhou University of Chinese Medicine Animal Care and Use Committee (Guangzhou, China), and conducted according to the ethical standards and national guidelines.

Coronaviruses (CoVs), a family of enveloped positive-sense RNA viruses, are characterized by club-like spikes that project from their surface, unusually large RNA genome, and unique replication capability. CoVs are known to cause various potentially lethal human respiratory infectious diseases, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the very recent coronavirus disease 2019 (COVID-19) outbreak. Unfortunately, neither drug nor vaccine has yet been approved to date to prevent and treat these diseases caused by CoVs. Therefore, effective prevention and treatment medications against human coronavirus are in urgent need. In the past decades, many natural compounds have been reported to possess multiple biological activities, including antiviral properties. In this article, we provided a comprehensive review on the natural compounds that interfere with the life cycles of SARS and MERS, and discussed their potential use for the treatment of COVID-19., Graphical abstract Chinese herbal medicines and natural compounds possess promising antiviral effects against Human coronaviruses (HCoVs) and provide a rich resource for novel antiviral drug development. This review provides an update on natural compounds against HCoVs and summarizes the active natural compounds and their possible action mechanisms.Image 1

The results and data availability of vaccine trials directly affect the decisions of healthcare providers, the public, and policymakers as to whether the vaccine should be applied. However, the reporting and data sharing level of COVID-19 vaccine studies are not clear.A cross-sectional study was conducted. A systematic search up to 9 May 2021 in 12 databases and an updated search to 6 July 2021 were conducted in the Cochrane Living Systematic Review and Network Meta-Analysis database to identify COVID-19 vaccine trials. The basic characteristics of included trials were summarized. The reporting level was assessed according to the CONSORT checklist. The data sharing level was assessed by open science practices. Types of incomplete reporting including protocol deviation, lack of primary outcomes clarity, and the omission of harms were analyzed.Finally, thirty-six COVID-19 vaccine articles reporting on 40 randomized controlled trials were included in this analysis. Based on the CONSORT checklist, the mean reporting score was 29.7 [95% confidence interval 28.7, 30.7]. Thirty-one articles (31/36, 86.1%) had data sharing statements, twenty-five articles (25/36, 69.4%) provided access to the source data. Twenty-seven articles (27/36, 75.0%) had protocol deviation, lack of primary outcomes clarity, or the omission of harms.The reporting and data sharing level of COVID-19 vaccine trials were not optimal. We hope that the reporting and data sharing of future trials will be improved. We recommend establishing a comprehensive, accurate data sharing system for future vaccine trials.This work was supported by the National Key RD Program of China (2019YFC1710400; 2019YFC1710403).

Polysaccharides are considered the main active ingredient for the immune-enhancing effect of Radix Astragali, which is popularly used as medicinal food supplementary. The signal pathways involved in immune-enhancing effect remain unclear. This study is to investigate the role and regulation relation of Akt pathway with downstream kinases of TLR4 receptor in macrophages induced by Astragalus polysaccharide, RAP. The results showed that RAP induced phosphorylation of Akt, NFκB, IRF3 and MAPKs in RAW264.7 cells, and their individual inhibitors not only inhibited their inflammatory factors production and gene expression, but also suppressed the Akt phosphorylation, while Akt inhibitor exerted no effect on MAPKs, NFκB, and IRF3 phosphorylation. Taken together, these results suggested that Akt and IRF3 exerted activation role in RAP induced macrophage, and Akt exerted effect downstream of MyD88 dependent and independent pathway. This study will provide a deeper insight into the signal transduction induced by Astragalus polysaccharides.

Migraine is one of the most common chronic neurological disorders worldwide. Current clinical treatment mainly aims to relieve symptoms, and the outcome is primarily evaluated on subjective parameters with a lack of comprehensive and objective evaluation criteria. The development of a core outcome set (COS) may offer a solution to the problems with evaluating the outcome of treatments for migraine. A total of 57 outcome indicators were obtained from the systematic review and semi-constructed interviews. After the two-round Delphi survey and analytic hierarchy process were used to assess the weight of each outcome, 16 core outcomes of acupuncture treatment for migraine treatment were selected. The COS evaluates the degree of relief provided by acupuncture therapy in terms of pain level and symptoms and provides a comprehensive and multidimensional assessment of quality of life, sleep quality, and mental health from the perspective of pain and it presented here could guide the application and precise evaluation of treatment for migraine. Funding Statement: This research was funded by the National key R&D Program of China (No. 2018YFC1707604) and the National Natural Science Foundation of China (No. 81674150). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: Ethical approval was obtained from the ethics committee of Beijing university of Chinese medicine (Approval no. DZMEC-KY-2018-44).Written informed consent for publication of our research details was obtained from the patients.

The Industrial Internet of Things (IIoT) has expanded worldwide rapidly, which brings key devices and applications of IIoT under a trustworthy umbrella that reinforces secure and safe IIoT services have never been more important. However, there are few effective methods for assessing the trustworthiness of IIoT networks and services, which may lead to a compromised system and massive decreases in productivity, or even catastrophic consequences. Complex networks have emerged to be a promising method to assess the trustworthiness of IIoT because they can reveal the latent features of networks and services. Enlightened by the potential of complex networks, a cloud-fog-edge computing paradigm for IIoT is presented and mapped to multilayer networks. Furthermore, we propose a Trustworthiness Assessment with Entropy (TAE) method, which quantitatively analyzes the topological characteristics of the IIoT networks and services. Experimental results on synthetic and real-world datasets present a comprehensive assessment of IIoT trustworthiness with the qualitative and quantitative analysis of von Neumann entropy, which proves the feasibility and robustness of the proposed method.

Our previous study demonstrated that a combination of alternative medicine berberine and conventional 5-aminosalicylic acid (5-ASA) showed promise to be a novel therapeutic strategy for ulcerative colitis (UC). This present study aims to sketch the pre-clinical toxicity profile of this combination (1:10 dose ratio) on mice. In acute toxicity test, the determined median lethal dose (LD50) was 278.7 mg/kg berberine plus 2787 mg/kg 5-ASA. The results from subacute toxicity test demonstrated that no toxic signs of clinical symptoms, no significant changes in hematological or biochemical parameters were detected in mice treated with 14 + 140, 28 + 280 or 56 + 560 mg/kg of berberine plus 5-ASA treatment. Histological examinations revealed that accompanied with an increase in spleen weight, frequently recorded enlargement and white pulp hyperplasia of spleen were detected in mice when exposed to three doses of combination treatments. Further in vitro assessment suggested that the spleen toxicity was originated from berberine by its inhibition in cell viability and cell proliferation of lymphocytes. The results of this study indicate that the combination of berberine and 5-ASA shows a slight toxic effect on spleen, suggesting that this combination should be used with caution for patients.

Introduction Functional dyspepsia is one of the typical functional gastrointestinal disorders and can be further categorized into postprandial distress syndrome and epigastric pain syndrome. The clinical response to conventional medicine treatment is unsatisfactory so that a majority of the population will seek help from Traditional Chinese Medicine. In clinical practice JianPi’I, derived from a classical TCM formula Xiangshaliujunzi decoction, appears to have a satisfactory effect on functional dyspepsia. Therefore, in order to further verify the benefit of JianPi’I, we designed a strict clinical trial to evaluate the safety and efficacy of JianPi’I in postprandial distress syndrome patients. Methods This is a 10-week, multicenter, randomized, double-blinded, placebo-controlled trial. Eligible 144 patients will randomly be assigned to JianPi’I or placebo. The primary outcome is the change in the postprandial discomfort severity scale from baseline to treatment endpoint. The secondary outcomes include the changes in the clinical global impression scale, Traditional Chinese Medicine symptoms scores, MOS 36-Item Short-Form Health Survey and gastric emptying from baseline to treatment endpoint. Discussion The main ingredients of JianPi’I contain Radix Codonopsis (Dangshen), Rhizoma Atractylodis Macrocephalae (Baizhu), Poria (Fuling), Fructus Amomi (Sharen), Radix Glycyrrhizae (Gancao), Radix Aucklandiae (Muxiang), Pericarpium Citri Reticulatae (Chenpi), and Rhizoma Pinelliae (Banxia), which are expected to alleviate symptoms of postprandial distress syndrome. This randomized placebo-controlled trial will comprehensively examine the efficacy and safety of JianPi’I in postprandial distress syndrome patients, and aim to provide a new treatment option for clinical practice in postprandial distress syndrome management.

Ultrasound treatment was applied to modify the physicochemical properties of an exopolysaccharide from mycelial culture of Schizophyllum commune. Molecular weight (MW) degradation, viscosity and anti-inflammatory property of ultrasonic treated polysaccharide were optimized with response surface methodology. The best ultrasonic parameters were obtained with a three-variable-three-level Box-Behnken design. The optimized conditions for efficient anti-inflammatory activity are initial concentration at 0.4%, ultrasonic power at 600W, and duration of ultrasonic irradiation for 9min. Under these conditions, the nitric oxide inhibition rate was 95±0.03% which agreed closely with the predicted value (96%). Average MW of polysaccharide decreased after ultrasonic treatments. The viscosity of degraded polysaccharide dropped compared with native polysaccharide. The anti-inflammatory activity was improved by ultrasound treatment. The results suggested that ultrasound treatment is an effective approach to decrease the MW of polysaccharide with high anti-inflammatory activity. Ultrasonic treatment is a viable modification technology for high MW polymer materials.

Introduction The formula of MaZiRenWan (MZRW) has been commonly used in Chinese medicine to treat constipation. Our previous studies have showed benefits in terms of increased bowel movement, relief in the severity of constipation and straining of evacuation when compared with placebo. However, the lack of studies on its safety, tolerability, system exposure and pharmacokinetics making it difficult to obtain a consistent picture of its mechanism of action. Methods/design This is a randomized, open-labelled, three-arm phase 0/1 clinical trial. After the run-in period, eligible healthy subjects will be randomized assigned in a ratio of 1:1:1 to receive 5.0 g, 7.5 g, 10 g q.d. of MZRW. The primary outcome will be the number of participants with adverse events as a measurement of safety and tolerability among three doses of MZRW. Secondary outcome will be the clearness of pharmacokinetic parameters of main active ingredients in human sample, include the area under the plasma concentration-time curve ( AUC ), the peak plasma concentration of an ingredient after administration ( C max ), the time to reach C max ( t max ), the elimination half-life ( t 1/2 ) and clearance ( CL ). Ethics and dissemination The study was approved by Hong Kong Baptist University Ethics Committee on the Use of Human Subjects for Teaching and Research (Approval no. HASC/13-14/0017) and was registered with an identifier (NCT02359396) in Clinical Trial.gov. The potential risks incurred by study participants will be reported to the public and the study results will be released to the investigators, patients and the general medical community.

Tumour growth is closely related to the development of new blood vessels to supply oxygen and nutrients to cancer cells. Without the neovascular formation, tumour volumes cannot increase and undergo metastasis. Antiangiogenesis is one of the most promising approaches for antitumour therapy. The exploration of new antiangiogenic agents would be helpful in antitumour therapy. Quinoline is an aromatic nitrogen compound characterized by a double-ring structure which exhibits a benzene ring fused to pyridine at two adjacent carbon atoms. The high stability of quinoline makes it preferable in a variety of therapeutic and pharmaceutical applications, including antitumour treatment. This work is to examine the potential antiangiogenic activity of the synthetic compound 2-Formyl-8-hydroxy-quinolinium chloride. We found that 2-Formyl-8-hydroxy-quinolinium chloride could inhibit the growth of human umbilical vein endothelial cells in vitro. Using the diethylnitrosamine-induced hepatocarcinogenesis model, 2-Formyl-8-hydroxy-quinolinium chloride showed strong antiangiogenic activity. Furthermore, 2-Formyl-8-hydroxy-quinolinium chloride could inhibit the growth of large Hep3B xenografted tumour from the nude mice. We assume that 2-Formyl-8-hydroxy-quinolinium chloride could be a potential antiangiogenic and antitumour agent and it is worthwhile to further study its underlying working mechanism.

Ethnopharmacological relevance Polysaccharides of Radix Astragali (Astragalus membranaceus (Fisch) Bge.; Huangqi) are able to induce cytokine production of macrophages and are considered the main active ingredient for the immune-enhancing effect of this commonly used medicinal herb. Aim of study To investigate the molecular mechanism of immunomodulating activities of a reported Astragalus polysaccharide, RAP, which is a hyperbranched heteroglycan with average molecular weight of 1334 kDa. Materials and methods The cytokine production of RAW264.7 cells were analyzed by using ELISA assays while cell viability was assessed by MTT method. Western blot analysis was used for determining protein contents of mitogen-activated protein kinases (MAPKs). In addition, the level of IL-6, iNOS, and TNF-α mRNA was determined by RT-PCR. Results It has been found that RAP itself did not have any cytotoxic effect on mouse mammary carcinoma 4T1 cells, but it significantly enhanced cytotoxicity of the supernatant of RAW264.7cells on 4T1 cells. Furthermore, RAP enhanced the production of NO and cytokines in RAW264.7 cells, and significantly up-regulated gene expressions of TNF-α, IL-6, iNOS. All these bioactivities were blocked by the inhibitor of TLR4 (Toll-like receptor 4), suggesting that TLR4 is a receptor of RAP and mediates its immunomodulating activity. Further analyses demonstrated that RAP rapidly activated TLR4-related MAPKs, including phosphorylated ERK, phosphorylated JNK, and phosphorylated p38, and induced translocation of NF-κB as well as degradation of IκB-α. These results are helpful to better understand the immunomodulating effects of Radix Astragali. Conclusions RAP may induce cytokine production of RAW264.7 cells through TLR4-mediated activation of MAPKs and NF-κB.

Introduction Insomnia in Chinese Medicine can be defined as inability to sleep or inability to relax when lying down. Insomnia is common among people in Hong Kong and requires appropriate management. Approximately 39.4% of adults are thought to suffer from insomnia in Hong Kong, a significant proportion of whom seek Chinese Medicine (CM) therapies as supportive care. This article provides a CM clinical practice guideline (CPG) for insomnia to guide local licensed CM practitioners which can be beneficial by providing a reference point for medical decision makers as well as patients. Methods A systematic search of clinical research regarding CM treatments for insomnia was conducted. After data retrieval and evaluation, the guideline was drafted on the basis of clinical evidence, data mining, consensus of experts in Hong Kong and overseas, and synthesizing information by the process of assessment and consultation. Results Based on the results of data mining and consensus by experts, common patterns of insomnia included: transformation of liver depression into fire, harassment of interior phlegm-heat, yin deficiency with internal fire, dual deficiency of the heart and spleen and lack of interaction between the heart and kidney. The recommended CM herbal prescriptions were: Longdanxiegan decoction, Modified Wendan decoction, Huanglianejiao decoction, Renshenguipi decoction and Jiaotai pill respectively. Appropriate acupuncture points were also identified Conclusions This article provides the first CM CPG for insomnia for Hong Kong local use which will provide a milestone in the development of CM in Hong Kong. It may help standardize and secure CM clinical practice thus improving efficacy and safety of CM.

Hydrogen sulfide (H2S), like CO and NO, is an endogenous gas signal molecule that can play a vital role in many physiological processes. Therefore, it's of great significance to study the efficient and sensitive imaging technology of H2S in vivo. Copper is an essential trace element in the human body that is very important for many cellular functions and related metabolic processes. In this study we report the design of a peptide L (FITC-Ahx-His-Glu-Phe-His-NH2) that can act as an “On-Off-On” fluorescent chemical sensor to detect Cu2+ and S2−, and cysteine (Cys) and glutathione (GSH) can also replace Cu2+ from L-Cu system. The capability of this peptide fluorescent probe to detect H2S in HeLa cells is also evaluated.

Ethnopharmacological relevance Sigesbeckiae Herba (SH), a traditional anti-inflammatory Chinese herbal medicine, is originated from the plants of Sigesbeckia pubescens Makino (SP), S. orientalis L. (SO) and S. glabrescens Makino (SG). The current studies reported that the chemical constituents in the three species of plants were different. Aim of the study The aim of this study is to provide a systemic comparison on the anti-inflammatory effects and the underlying molecular mechanisms among the three plants based on their effects on nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) signal pathways in vitro. Material and methods Twenty-four batches of three Sigesbeckia herbs were collected from different regions of China and extracted with 50% ethanol. The distribution of 6 compounds in the 24 batches of SH extracts were characterized by UPLC analysis. The cytotoxicity of all extracts to RAW264.7 cells in the absence or presence of lipopolysaccharide (LPS) were examined by 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The anti-inflammatory effects of the extracts were investigated using Griess reagent and enzyme-linked immunosorbent assay. The underlying mechanisms of the representative samples (SP007, SO005 and SG003) for individual species were examined by western blotting and immunofluorescence staining. Results The estimated average sub-lethal dose (LD15) of SP, SO and SG on RAW264.7 cells were 181.7 ± 15.7, 291.5 ± 33.9 and 317.1 ± 16.3 μg/mL, respectively. In LPS-stimulated RAW264.7 cells, the inhibitory effects of SH species were determined to be SP > SO > SG on NO release, while SP ~ SO > SG on secretion of post-inflammatory cytokines (TNF-α, IL-6 and MCP-1). Moreover, suppression on LPS-induced excessive expressions of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), as well as the activation of NF-κB and phosphorylation of MAPKs were investigated to be associated to the anti-inflammatory effects for all SH species. Conclusions We firstly reported a systemic comparison on the anti-inflammatory properties for the three main plant origins of SH. Although SG showed lower toxicity and less anti-inflammatory effects compared with SP and SO in LPS-induced RAW264.7 cells, comparable inhibitory effects on NF-κB and MAPKs pathways and the reduction of LPS-induced iNOS and COX-2 were observed in the anti-inflammatory process for all Sigesbeckia plants.

Ma-Zi-Ren-Wan (MZRW) is a classic Chinese formula which has been used to treat human constipation in China for over 2000 years. In order to make good and rational use of this formula in the future, this paper presents the first attempt to track the pharmacokinetic features of MZRW in rat using rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Ten chemical components of MZRW, namely, rhein, emodin, aloe emodin, hesperidin, naringin, amygdalin, albiflorin, paeoniflorin, magnolol and honokiol, were simultaneously determined in rat plasma after a single oral administration (10g/kg body weight) of MZRW to rats. Geniposide and liquiritin were used as internal standards. The separation was performed on a Waters ACQUITY BEH C18 column (100mm×2.1mm, 1.7μm). The detection was conducted by multiple-reaction monitoring (MRM) in negative ionization mode. Two highest abundant MRM transitions without interference were optimized for each analyte. This method was well validated in terms of linearity, precision, accuracy, recovery, matrix effect and stability. All calibration curves had good linearity (r(2)>0.995) over the concentration range from 3.9 to 125.0ng/mL for emodin, 3.9-500.0ng/mL for amygdalin, 2.0-4000.0ng/mL for naringin and hesperidin, 3.9-2000.0ng/mL for magnolol, 7.8-2000.0ng/mL for rhein and 3.9-4000.0ng/mL for albiflorin, paeoniflorin, aloe emodin and honokiol. The intra-day and inter-day precision (relative standard deviation) was within 15%, the accuracy (relative error) ranged from -13.6% to 15.1%, and the lower limit of quantification in plasma ranged between 2.0ng/mL and 7.8ng/mL. Extraction recovery, matrix effect and stability were satisfactory. The validated method was successfully applied to a pharmacokinetic study of these ten compounds after oral administration of MZRW to rats. The pharmacokinetic parameters of each compound can facilitate clinical studies in the future.

One of the main active components from mushrooms was recently identified as β-glucan. Health-promoting β-glucans are an auspicious group of polysaccharides. β-Glucans from different sources such as cereals, yeast and grass have previously been documented. However, information on mushroom β-glucan is limited. This review summarizes the extraction, purification, quantification, and structural characterization of β-glucans, along with chemical and biological activities from this compound from mushrooms, and the current status of this research area with a view for future directions.

Trans -resveratrol, also known as 3,5,4′-trihydroxy- trans -stilbene, is a natural stilbenoid found at high concentration in skins of red grapes and berries. Over the recent years, it has been reported with a variety of beneficial effects such as antioxidant, anti-aging and anti-inflammatory bioactivities; thus often utilized as an active substance in human and veterinary therapeutics. In the current study, we aimed to delineate the mechanism of its anti-fibrotic action by means of various biochemical assays, such as immunofluorescent staining, real-time polymerase chain reaction and Western blotting analyses in a cellular model, the LTC-14 cells, which retain essential characteristics and morphological features of primary pancreatic stellate cells (PSCs). Our results demonstrated that the application of trans -resveratrol as low as 10 μM notably suppressed the mRNA and protein levels of different fibrotic mediators namely alpha-smooth muscle actin, type I collagen and fibronectin in the LTC-14 cells stimulated with transforming growth factor-beta, a well recognized pro-fibrotic inducer. Importantly, the mechanism of the anti-fibrotic action of trans -resveratrol was associated with a decrease in nuclear factor-kappaB activation and protein kinase B phosphorylation. In conclusion, our finding suggests that trans -resveratrol may serve as a therapeutic or an adjuvant agent in anti-fibrotic approaches and/or PSC-relating pathologies.

Ethnopharmacological relevance Inflammatory bowel disease (IBD) is generally associated with a set of debilitating symptoms including abdominal pain, tenesmus, diarrhea and bloody stool. The standard approaches for treating IBD, which are the application of pharmaceuticals, are often unsatisfactory. IBD patients may suffer from repeated relapses and even exacerbation after taking these medications. Thus, patients are increasingly seeking relief through the use of complementary and alternative medicines. Aim of study To provide scientific ground for the mode of actions of a Chinese medicinal formulation—modified ZenWu Decoction (MZWD) in ulcerative colitis. Materials and methods C57BL6 mice were fed with 3 cycles of 2% dextran sulfate sodium (DSS) in drinking water for the induction of chronic colitis and then given MZWD at 17.47 g/kg/day. Effects of MZWD were evaluated by histopathological and biochemical assays. Results When MZWD was given, inflammatory responses namely immune-cell infiltration, elevated serum levels of pro-inflammatory cytokines and mucosal lesions were notably suppressed. Further, MZWD treatment attenuated the activation of nuclear factor-kappaB (NF-κB), the vital regulator of inflammatory cascades, while lessening the degradation of I-kappaB-alpha and reducing the activity of protease-activated receptor 2 in DSS-induced colonic tissues. Consequently, diarrhea, bloody stool and colon shortening were reduced whilst mucosal integrity was improved in MZWD-treated colitis mice. Conclusions Our findings suggest that MZWD is a potential remedy for treating IBD, and the mechanism of its efficacy is an anti-inflammatory effect associated with the suppression of the NF-κB pathway.

Introduction Health information technology (HIT) has been used to assist health care professionals in managing clinical tasks and conducting research. In recent years, HIT has also been applied to traditional Chinese medicine (TCM). In order to identify appropriate approaches to facilitate HIT adoption in TCM, a survey study was conducted to investigate the views of practitioners towards computer use in TCM. Methods Questionnaires were administered from June to July 2013. Responses were collected from two groups (private practitioners and academics). Descriptive analyses were conducted. Results The response rate for the private practitioner group was 65.49%. Although only 31.76% of private practitioners had used computer programmes for TCM practice, 72.30% of respondents agreed that computer programmes should be used in the clinical setting. In contrast, HIT adoption was high (95.00%) in the academic group. All respondents in the academic group agreed that computer programmes should be used in the clinical setting and research. Conclusions Respondents from different TCM groups were generally supportive of the use of HIT in clinical practice. As views towards HIT use varied between the TCM groups, different approaches to HIT adoption is needed to suit the needs of TCM professionals in different settings.

Introduction Electronic prescribing (e-prescribing) can potentially improve the quality of patient care in traditional Chinese medicine (TCM) by facilitating clinical tasks. Published survey studies investigating e-prescribing use were mostly conducted in conventional medicine, but these findings cannot be entirely generalised to TCM practice. It is important, therefore, to investigate e-prescribing in the TCM context. Purpose To investigate Chinese medicine students’ attitudes and perceptions of e-prescribing use in Hong Kong. Method Questionnaires were distributed to TCM students in three Hong Kong universities between January and May 2013. There were 259 participants in this study. Questionnaires were distributed and collected during lectures. The data was analysed using descriptive statistics. Results The overall response rate was 89.3%. Only 21.2% of survey respondents had previously used an e-prescribing system. However, 86.5% of the respondents stated they want to use e-prescribing after they qualify as TCM practitioners. Patient care efficiency was rated as the most favourable outcome of e-prescription compared to handwritten prescriptions. The reliability of the e-prescribing system was rated as a major concern. Conclusion TCM students in Hong Kong were generally supportive of e-prescribing uptake. However, this study raised concerns and potential barriers to e-prescribing use. Factors that may facilitate e-prescribing uptake in TCM are also suggested. Further studies investigating TCM practitioners’ views will be required to identify further facilitators and barriers to the uptake of e-prescribing.

β-Glucans from fungi exhibit a broad spectrum of biological activities including anti-tumor, immune-modulating and anti-inflammatory properties. The anti-inflammatory effect is mediated through the regulation of various inflammatory cytokines, such as nitric oxide (NO), interleukins (ILs), tumor necrosis factor alpha (TNF)-α, interferon gamma (INF)-γ as well as non-cytokine mediator, prostaglandin E2 (PGE2). Up to now, the anti-inflammatory activity of β-glucans has received little attention. It is worthwhile to investigate the anti-inflammatory properties of fungal β-glucans in a separate review, discussing in vitro studies, animal studies and human studies on anti-inflammation effects of fungal β-glucans, as well as the structure-anti-inflammatory activity relationships.

This paper reports a way to increase the production yield of counter-current chromatography by using two-phase solvent systems in sample pretreatment. This strategy succeeds in the case of anti-EV71 saponin preparation from Anemarrhena asphodeloides. Briefly, 15 g of water extract was refined by solvent partition with ethyl acetate/1-butanol/water (1:4:5, v/v) to yield 4.17 g of the upper part, which in turns yielded 635 mg of timosaponin B-II (purity 96.5%) and 672 mg of anemarsaponin B (97.8%) after gradient CCC separation with 1-butanol/water (containing 0.01 mol/L CuSO4 in water, 1:1, v/v) and ethyl acetate/1-butanol/water (3:17:20, v/v/v). In a similar way, the ethanol extract (8 g) was partitioned between the diphase solvent system of ethyl acetate/1-butanol/water (4:1:5) to get 2.16 g of refined fraction and yielded 358 mg of timosaponin A-III (96.4%) by CCC elution using ethyl acetate–methanol–water (4:1:5, v/v/v). To remove mangiferin, the salt CuSO4 was added; it formed a complex with mangiferin, thereby enlarging the separation coefficient between mangiferin and timosaponin B-II.

As an efficient catalyst, the [Ir(COD)Cl]2/NMDPP complex has been successfully applied to promote the asymmetric ring opening reaction of oxabenzonorbornadienes with various amines, which afforded the corresponding products in good yields (72–98%) with good enantioselectivities (80–90% ee).

This study reports the synthesis and characterization of quinoline derivatives. The synthesized quinoline compounds were applied to the dyeing treatment of acrylic fabrics. The color fastness to washing and light of quinoline compound-dyed fabrics was examined. Human skin HaCaT cell line was also used for the skin cytotoxicity evaluation of the quinoline compound-dyed acrylic fabrics.

Lactococcosis is prevalent on grey mullet (Mugil cephalus) in Hong Kong aquaculture resulting in serious economic loss. A compound formulation of Traditional Chinese Medicines (TCM) (modified Huanglian Jiedu decoction (HLJDD)) comprising Rhizoma coptidis, Radix scutellaria, Cortex phellodendri, Fructus gardeniae, Fructus forsythiae and Flos lonicerae japonicae (in a ratio of 3:2:2:3:3:5) were applied as feed supplements to deal with the disease. The Nitroblue tetrazolium activity in blood, bactericidal activity and total immunoglobulin in plasma were significantly enhanced after feeding 1% of this TCM for 28 days. The disease resistances to Lactococcus garvieae in 1% and 2% TCM feeding groups were significantly enhanced. In the in vitro study, the modified HLJDD also activated the plasma bactericidal activities (p

Ethnopharmacological relevance Saussurea laniceps Hand.-Mazz. (SL) has long been used under the herbal name Tibetan “Snow Lotus” for the treatment of rheumatoid arthritis, stomachache and dysmenorrhea in Tibetan folk medicine. Since herbal medicine (HM) is a synergistical system with multiple components, both of the metabolism and pharmacokinetic studies of HM are interdependent. This study aimed to develop an integrated strategy based on the UPLC–DAD–QTOF-MS technique for metabolism and pharmacokinetic studies of HM. Material and methods SL was used here as a test herb to verify the feasibility of the proposed strategy. SL was administered to rats, then, the blood plasma, urine and feces were analyzed to determine the metabolic profiles. Using our strategy, umbelliferone and scopoletin were evaluated to be the key bioactive components. Their pharmacokinetic parameters were measured and biotransformation pathways were elucidated. Results After oral administration of SL to rats, 17 components in blood, 10 components in urine and 2 components in feces were identified and characterized using our UPLC–DAD–QTOF-MS method. Umbelliferone, scopoletin and their metabolites were found to be the major components involved in the metabolism process. Literature reports also suggest that umbelliferone and scopoletin are responsible for the therapeutic effects of SL, thus these two components were selected as the active markers for pharmacokinetic study. In the test of validity, the established method presented good linearity with R2>0.99. The relative standard deviation value was below 13.9% for precision, and recovery studies for accuracy were found to be within the range 91.8–112.5%. Conclusion The present strategy offers, simultaneously, precision in quantitative analysis (metabolism study) and accuracy in quantitative analysis (pharmacokinetic study) with greater efficiency and less costs, which is therefore reliably used for integrated metabolism and pharmacokinetic studies of HM.

Gelatin/Collagen-based matrix and reservoir nanoparticles require crosslinkers to stabilize the formed nanosuspensions, considering that physical instability is the main challenge of nanoparticulate systems. The use of crosslinkers improves the physical integrity of nanoformulations under the-host environment. Aldehyde-based fixatives, such as formaldehyde and glutaraldehyde, have been widely applied to the crosslinking process of polymeric nanoparticles. However, their potential toxicity towards human beings has been demonstrated in many previous studies. In order to tackle this problem, D-glucose was used during nanoparticle formation to stabilize the gelatin/collagen-based matrix wall and reservoir wall for the deliveries of Calendula officinalis powder and oil, respectively. In addition, therapeutic selectivity between malignant and normal cells could be observed. The C. officinalis powder loaded nanoparticles significantly strengthened the anti-cancer effect towards human breast adenocarcinoma MCF7 cells and human hepatoma SKHep1 cells when compared with the free powder. On the contrary, the nanoparticles did not show significant cytotoxicity towards normal esophageal epithelial NE3 cells and human skin keratinocyte HaCaT cells. On the basis of these evidences, D-glucose modified gelatin/collagen matrix nanoparticles containing C. officinalis powder might be proposed as a safer alternative vehicle for anti-cancer treatments.

Introduction An increasing number of clinical practice guidelines (CPGs) in traditional Chinese medicine (TCM) for rheumatoid arthritis (RA) have been issued, and all have been developed in China but their quality is unclear. This study aimed to systematically review the quality and consistency of recommendations on the TCM CPGs for RA in China using the AGREE II instrument. Methods TCM CPGs identified from five electronic databases and hand searches through related handbooks published between January 1990 and December 2012. The CPG were categorized into Evidence Based (EB) guideline, Consensus Based with no explicit consideration of Evidence Based (CB–EB) guideline and Consensus Based (CB) guideline according to the method reported previously. Four reviewers independently appraised the CPGs based on the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument, and compared the recommendation on TCM pattern (Zheng) classification and treatment. Results Five TCM CPGs satisfied the inclusion criteria. The quality score of EB guideline was higher than CB–EB and CB guidelines. Five TCM patterns in the CPGs were recommended in the EB CPG. The herbal preparations including Tripterygium wilfordii recommended in the EB CPG were mostly recommended for RA treatment. The recommendations on non-drug management in the CPGs were fairly consistent, and the recommendations are different based on the different TCM patterns accordingly. Conclusions EB CPG for RA treatment in TCM show higher quality with measurement of AGREE II instrument, and it suggested that TCM CPG could be better developed with clinical evidence.

Objectives Casein kinase 2 interacting protein 1 (CKIP-1) is a newly discovered intracellular negative regulator of bone formation without affecting bone resorption. In this study, we aimed to identify a cross-species siRNA sequence targeting CKIP-1 to facilitate developing a novel RNAi-based bone anabolic drug for reversing established osteoporosis. Methods Eight specifically designed cross-species CKIP-1 siRNA sequences were screened in human, rhesus, rat and mouse osteoblast-like cells in vitro to identify the optimal sequence with the highest knockdown efficiency. The effect of this optimal siRNA sequence on osteogenic differentiation and matrix mineralization was further examined in osteoblast-like cells across different species, followed by an immunogenicity assessment in human peripheral blood mononuclear cells in vitro. The intra-osseous localization and silencing efficiency of the optimal siRNA were examined in vivo using a biophotonic system and real-time polymerase chain reaction, respectively. The RNAi-mediated cleavage of the CKIP-1 transcript was confirmed by rapid amplification of the 5′ cDNA ends in vivo. Furthermore, the effect of the optimal siRNA sequence on osteogenic differentiation, bone turnover biomarkers, bone mass and micro-architecture parameters was investigated in healthy and osteoporotic rodents. Results The CKIP-1 siRNA sequence (si-3) was identified as the optimal sequence, which consistently maintained CKIP-1 mRNA/protein expression at the lowest level across species in vitro. The si-3 significantly increased mRNA expression levels of osteoblast phenotypic genes and matrix mineralization across species without inducing an immunostimulatory activity in vitro. The intra-osseous localization and RNAi-mediated CKIP-1 silencing with high efficiency were confirmed in vivo. Periodic intravenous injections of si-3 promoted mRNA expression of osteoblast phenotypic genes, enhanced bone formation, increased bone mass and elevated serum level of bone formation marker without raising urine level of bone resorption marker in the healthy rodents. Moreover, the si-3 treatment promoted bone formation, improved trabecular micro-architecture and reversed bone loss in the osteoporotic mice. Conclusions The identified optimal CKIP-1 siRNA sequence (si-3) could promote osteogenic differentiation across species in vitro, stimulate bone formation in the healthy rodents and reverse bone loss in the osteoporotic mice.

Introduction Pattern differentiation is a critical component for traditional Chinese medicine (TCM) diagnosis and treatment. However, the issue of whether pattern differentiation is appropriately applied in TCM interventional trials, including Chinese herbal medicine (CHM) interventions and non-herbal TCM interventions, is unclear. The aim of this study was to i) systematically review the current status of pattern differentiation used in WHO-registered clinical trials for different types of TCM interventions; and ii) provide suggestions for improving the use of pattern differentiation in future clinical trial design. Methods The World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) database was searched for all TCM interventional trials registered up to 31 December 2017. In this systematic review trials with a TCM pattern differentiation in their design were included. Descriptive statistics were collated to demonstrate the characteristics of pattern differentiation applied for different TCM interventional trials. Results Among 2955 TCM interventional trials registered during 1999–2017, 376 (12.7%) trials included pattern differentiation. Of 376 trials, the use of pattern differentiation was identified in; –the title (30.6%), objective (50.5%), participants inclusion (100%), outcomes (43.6%) and study background (12.5%). Further, 85.4% reported the specific name of the TCM intervention, 10.6% provided the intervention’s targeted pattern, 83.8% reported the specific name of the TCM pattern, 7.2% presented diagnostic criteria for the pattern studied, and 19.1% adopted a pattern-related outcome as primary outcome for evaluation. Conclusion The reporting and application of pattern differentiation in TCM trials were inadequate and confusing, which was mainly due to lack of clarity regarding study design, objectives, diagnostic criteria and outcomes.

Hemp seed soft gel capsule (HSSGC) is a modernised dosage form that is derived from a traditional Chinese patent medicine, Hemp Seed Pills (HSP). Two dosage forms claim the same therapeutic effects; however, their chemical components and chemical equivalency are unclear. In the present study, an ultra performance liquid chromatography coupled with time-of-flight mass spectrometry (UHPLC-ToF–MS)-based chemical profiling approach was proposed to rapidly evaluate the chemical differences between HSP and HSSGC as model dosage forms. Samples of the two dosage forms were subjected to UHPLC-ToF–MS analysis. The datasets of retention time ( T R ) and mass-to-charge ratio ( m / z ) pairs, ion intensities and sample codes were processed with principal component analysis (PCA) and partial least squares discriminate analysis (PLS-DA) to holistically compare the difference between these two dosage form samples. A clear classification trend was observed in the score plot, and a loading bi-plot was generated in which the variables are correlated with the group and the samples that were observed. The important chemical components that caused differences among the samples were explored with a Variables Importance Projection (VIP) index. Using the proposed approach, global chemical differences were found between the two dosage forms and among samples of the same dosage form. The most important components that are related to the differences were identified and most of them were attributed to Fructus Aurantii Immaturus. It is suggested that this newly established approach could be used for pre-clinical trial chemical equivalence study or the quality evaluation of the traditional medicinal products with large variations in quality.

Developing new pharmaceuticals requires massive amounts of time, money and efforts. The key step is how to find a safe and effective entity for a disease condition and how to develop it as new drug effectively. Unfortunately, the FDA's rate of approving new entities has declined dramatically in the last three decades. There is a strong need to review the current strategy and to optimize process in developing new drugs, both to shorten the process and increase the success rate. Chinese medicine has used natural products to treat patients for thousands of years, and Chinese medicine practitioners have chronicled the patients and treatment methods for thousands of years. There is much information that has not yet been used. The success stories of artimisinin and arsentic trioxide are wonderful examples of how the annals of Chinese medicine can provide leads for discovering new drugs. This paper argues that the annals of Chinese medicine are valuable and describes how they can be used in modern drug discovery. The major topics addressed are: (i) why Chinese medicine is a rich resource for finding new drugs; (ii) how to identify a potential valuable record from Chinese medicine annals; (iii) when a potential valuable record is identified from annals, how to proceed; and (iv) both why and how the approach used for chemical drugs should be revised for drugs based on the historical documents related to herbal medicine. In conclusion, we argue here that the annals of Chinese medicine offer not only a rich resource for new drugs, but also several centuries of patient data with regard to safety and efficacy, that in effect represent pilot studies. Acknowledging and using these data can shorten new drug discovery time and improve efficiency of the drug development process, bringing more effective, safe drugs to market much more quickly and cheaply.

Metabolomics, the exponentially developing technique, could provide a systemic mapping in toxicology by directly measuring small molecular metabolites. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) was found to be neurotoxic in mammalian animals. In this study, we employed liquid chromatography/quadrupole time-of-flight mass spectrometry for non-targeted analysis of metabolic profiling in hippocampal sample sets of the rats exposed to TCDD. Hippocampal metabolome from different ages of the healthy rats (4-week, 12-week and 20-week) was also deciphered. The relationship between the two tested cases was unlocked to delineate TCDD toxicity associated with ageing. Tandem mass spectrometry fragmentation in conjunction with metabolic database searching and compared to authentic standards was utilized for metabolite identification. As a consequence, the reduced levels of phenylalanine and leucine/isoleucine as well as the up-regulation of inosine and hypoxanthine were highlighted for understanding of TCDD toxicity related to age in rats and the trajectory was depicted by principal components analysis.

Though acupuncture has long been used to treat various kinds of pain, its mechanisms remain partly understood. Our recent study has shown that it may inhibit cyclooxygenase-2 (COX-2) in the spinal dorsal horn where COX-2 is upregulated after the development of neuropathic pain following spinal nerve ligation (SNL). The current study directly compared the effect of acupuncture with COX-2 inhibitor celecoxib in the spinal cord after SNL in rats. After L5 SNL, the rats were treated either with acupuncture applied to Zusanli (ST36) and Sanyinjiao (SP6) bilaterally with or without electrical stimulation (2 Hz, 0.5-1-2 mA) four times over 22 days, and/or celecoxib fed daily. Paw-withdrawal-threshold to mechanical stimulation and paw-withdrawal-latency to thermal test were tested for neuropathic pain at four intervals following the treatments in comparison with the pre-treatment and non-treatment controls. The results demonstrate that electroacupuncture (EA) had a long lasting and better analgesic effect than celecoxib in reducing neuropathic hypersensitivity. Though COX-2 expression in the spinal L4-L6 dorsal horn by immunostaining was significantly reduced by acupuncture just as well as by celecoxib, the superior analgesic mechanism of acupuncture appears well beyond COX-2 inhibition alone.

The fact that many cancer patients take herbal medicine, including Chinese herbal medicine, together with chemotherapy is well known. The potential for side effects resulting from concurrent use of these two different treatment modalities requires physicians to be aware of the potential risks and benefits that might arise. This study searched available evidence for herb-drug interaction in cancer therapy and identified 168 articles. Little direct evidence for such interaction could be found, whereas there is some indirect evidence for benefit. Hence, most of the concern about herb-drug interaction in chemotherapy appears to be theoretical. To resolve this discrepancy, evidence-based studies should be undertaken to document the positive and/or negative effects of the concomitant use of herbs with anticancer chemotherapeutic drugs. As evidence accumulates, it would be helpful to set up an internationally accessible database to document the use of Chinese medicine herbs with anticancer drugs. Once this information is collected, efforts should be made to educate health care professionals and patients about the use of Chinese herbal medicine together with Western drugs in treating cancer.

Paeoniflorin (PF), a chief active ingredient in the root of Paeonia lactiflora Pall (family Ranunculaceae), is effective in relieving colorectal distention (CRD)-induced visceral pain in rats with visceral hyperalgesia induced by neonatal maternal separation (NMS). This study aimed at exploring the underlying mechanisms of PF's analgesic effect on CRD-evoked nociceptive signaling in the central nervous system (CNS) and investigating whether the adenosine A 1 receptor is involved in PF's anti-nociception. Results : CRD-induced visceral pain as well as phosphorylated-extracellular signal-regulated protein kinase (p-ERK) and phospho-cAMP response element-binding protein (p-CREB) expression in the CNS structures of NMS rats were suppressed by NMDA receptor antagonist dizocilpine (MK-801) and ERK phosphorylation inhibitor U0126. PF could similarly inhibit CRD-evoked p-ERK and c-Fos expression in laminae I–II of the lumbosacral dorsal horn and anterior cingulate cortex (ACC). PF could also reverse the CRD-evoked increased glutamate concentration by CRD as shown by dynamic microdialysis monitoring in ACC, whereas, DPCPX, an antagonist of adenosine A 1 receptor, significantly blocked the analgesic effect of PF and PF's inhibition on CRD-induced p-ERK and p-CREB expression. These results suggest that PF's analgesic effect is possibly mediated by adenosine A 1 receptor by inhibiting CRD-evoked glutamate release and the NMDA receptor dependent ERK signaling.

This study presented a capillary zone electrophoresis (CZE) method for the analysis of trace amount of neurotransmitters glutamate (Glu) and aspartate (Asp) in the microdialysates of rat periaqueductal gray matter (PAG). Glu and Asp were derivatized with the fluorescent agent 5-carboxyfluorescein N-succinimidyl ester (CFSE) for the first time and detected by laser-induced fluorescence (LIF) after separation by CZE. The concentration detection limits (S/N=2) were 6.9x10(-10)M and 8.1x10(-10)M for Glu and Asp, respectively. The repeatability (expressed as RSD) of the migration times of CFSE-amino acid were better than 0.5%, and not higher than 1.5% even over the period of 1 month. This method was applied to quantify Glu and Asp in rat PAG microdialysates with the treatment of formalin injection, and the measured basal concentrations of Glu and Asp were (22.4+/-1.6)x10(-6)M and (0.9+/-0.1)x10(-6)M, respectively.

Neonatal maternal separation (NMS) has been shown to trigger alterations in neuroendocrine, neurochemical and sensory response to nociceptive stimuli along the brain–gut axis. These alterations may be the result of a cascade of events that are regulated by neurotrophic factors. Nerve growth factor (NGF), a member of the neurotrophin family, is essential for the development and maintenance of sensory neurons and for the formation of central pain circuitry. The present study aimed to investigate whether NMS causes changes in neuronal plasticity and the relationship of these changes in plasticity with the expression of NGF and its high affinity tyrosine kinase receptor A (TrkA) in the lumbosacral spinal cord in adult rats. Male Wistar rat pups were either subjected to 180 min daily of NMS or not handled (NH) for 13 consecutive days. The expression of NGF and TrkA was examined in NH and NMS rats with or without colorectal distention (CRD) as determined by Western blot analysis and immunohistochemistry. The present results of Western blot analysis indicated NMS and CRD have a significant effect on NGF protein level in the lumbosacral spinal cord of rats. Assessments of optical densities revealed that NMS enhanced TrkA-ir fiber densities in laminae I–III and laminae V–VI of rats in both conditions with or without CRD. Double immunofluorescence revealed that TrkA co-expressed with calcitonin gene-related peptide (CGRP) in afferent fibers, while no significant difference in terms of the intensity of TrkA-ir in these fibers was found among groups. Quantitative analysis of TrkA-ir neurons indicated a significant interactive effect of NMS and CRD on the mean number of TrkA-ir neurons in laminae V–VI of rats, in which significant difference was found between NMS+CRD and NH+CRD. Double immunofluorescence of TrkA and Fos showed that CRD has a significant effect on TrkA expression in Fos-positive neurons in laminae V–VI and lamina X of rats, while no significant difference was found between NMS+CRD and NH+CRD. These results demonstrate that NMS induced alterations in NGF protein level and TrkA expression in adult rat spinal cord and indicate that NGF is a crucial mediator for the changes in neuronal plasticity that occur in NMS-induced visceral hyperalgesia.

QFGJS is an herbal preparation, and its pronounced effectiveness in treating adjuvant-induced arthritis (AIA) has been previously demonstrated. We herein aimed to confirm its anti-arthritic effect on collagen-induced arthritis (CIA) in rats. CIA was established in female Wistar rats with intradermal injection of type II bovine collagen at the base of the tail of animals. CIA rats were treated daily with oral administration of different doses of QFGJS beginning on the day of the induction of arthritis (day 0, the prophylactic treatment) or on the day after the onset of arthritis (day 13, the therapeutic treatment) until day 30. The results showed that prophylactic treatment with QFGJS significantly suppressed the onset of arthritis, and therapeutic treatment with QFGJS markedly reduced paw swelling and ESR levels even in the established CIA. Radiologic and histopathologic changes in the arthritic joints were also significantly reduced in the QFGJS-treated versus vehicle-treated rats. Moreover, the serum levels of pro-inflammatory cytokines TNF-alpha, IL-1beta, and IL-6 were markedly lowered in the QFGJS-treated rats. Hence, our studies demonstrate the quality, safety, and effectiveness of QFGJS as an anti-arthritic agent, which makes QFGJS a strong candidate for further clinical trials on rheumatoid arthritis (RA) patients.