An Ethnopharmaceutical Study on the Hypolipidemic Formulae in Taiwan Issued by Traditional Chinese Medicine Pharmacies.

Globally, approximately one-third of ischemic heart diseases are due to hyperlipidemia, which has been shown to cause various metabolic disorders. This study was aimed to disassemble and analyze hypolipidemic formulae sold by traditional Chinese medicine (TCM) pharmacies. Using commonly used statistical parameters in ethnopharmacology, we identified the core drug combination of the hypolipidemic formulae, thereby exploring the strategy by which the Taiwanese people select hypolipidemic drugs. Most important of all, we preserved the inherited knowledge of TCM. We visited 116 TCM pharmacies in Taiwan and collected 91 TCM formulae. The formulae were mainly disassembled by macroscopical identification, and the medicinal materials with a relative frequency of citation (RFC) >0.2 were defined as commonly used medicinal materials. Subsequently, we sorted the information of medicinal materials recorded in the Pharmacopeia, searched for modern pharmacological research on commonly used medicinal materials using PubMed database, and visualized data based on the statistical results. Finally, the core hypolipidemic medicinal materials used in folk medicine were obtained. Of the 91 TCM formulae collected in this study, 80 traditional Chinese medicinal materials were used, belonging to 43 families, predominantly Lamiaceae. Roots were the most commonly used part as a medicinal material. There were 17 commonly used medicinal materials. Based on medicinal records in Pharmacopeia, most flavors and properties were warm and pungent, the majority traditional effects were "tonifying and replenishing" and "blood-regulating." Besides, the targeted diseases searching from modern pharmacological studies were diabetes mellitus and dyslipidemia. The core medicinal materials consisted of Astragalus mongholicus Bunge and Crataegus pinnatifida Bunge, and the core formulae were Bu-Yang-Huan-Wu-Tang and Xie-Fu-Zhu-Yu-Tang. In addition, 7 groups of folk misused medicinal materials were found. Although these TCMs have been used for a long period of time, their hypolipidemic mechanisms remain unclear, and further studies are needed to validate their safety and efficacy.

AeQTL: eQTL analysis using region-based aggregation of rare genomic variants.

Concurrently available genomic and transcriptomic data from large cohorts provide opportunities to discover expression quantitative trait loci (eQTLs)-genetic variants associated with gene expression changes. However, the statistical power of detecting rare variant eQTLs is often limited and most existing eQTL tools are not compatible with sequence variant file formats. We have developed AeQTL (Aggregated eQTL), a software tool that performs eQTL analysis on variants aggregated according to user-specified regions and is designed to accommodate standard genomic files. AeQTL consistently yielded similar or higher powers for identifying rare variant eQTLs than single-variant tests. Using AeQTL, we discovered that aggregated rare germline truncations in cis exomic regions are significantly associated with the expression of BRCA1 and SLC25A39 in breast tumors. In a somatic mutation pan-cancer analysis, aggregated mutations of those predicted to be missense versus truncations were differentially associated with gene expressions of cancer drivers, and somatic truncation eQTLs were further identified as a new multi-omic classifier of oncogenes versus tumor-suppressor genes. AeQTL is easy to use and customize, allowing a broad application for discovering rare variants, including coding and noncoding variants, associated with gene expression. AeQTL is implemented in Python and the source code is freely available at https://github.com/Huan-glab/AeQTL under the MIT license.

Effects of Chinese herbal medicines on dementia risk in patients with sleep disorders in Taiwan.

ETHNOPHARMACOLOGICAL RELEVANCE: Sleep disorders affect an estimated 150 million people worldwide and result in adverse health, safety, and work performance-related outcomes that have important economic consequences. In Taiwan, Chinese herbal medicine (CHM) is a complementary natural medicine and has been widely used as an adjunctive therapy. AIM OF THE STUDY: This study aimed to investigate the effect of CHM on dementia risk in patients with sleep disorders in Taiwan. MATERIALS AND METHODS: We identified 124,605 patients with sleep disorders between the ages of 20 and 60 years. Of these, 5876 CHM users and 5876 non-CHM users were matched according to age and gender. The chi-squared test, Cox proportional hazard model, Kaplan-Meier method, and log-rank test were used for the comparisons. Association rule mining and network analysis were applied to determine a CHM pattern specialized for sleep disorders. RESULTS: More CHM users did not use sleeping pills than non-CHM users. CHM users had a lower risk of dementia than non-CHM users after adjusting for age, gender, and sleeping pill use (hazard ratio (HR): 0.469, 95% CI = 0.289-0.760; p-value = 0.002). The cumulative incidence of dementia was lower among CHM users (long-rank test, p-value < 0.001). Association rule mining and network analysis showed that Ye-Jiao-Teng (YJT; Caulis Polygoni Multiflori; Polygonum multiflorum Thunb), Suan-Zao-Ren-Tang (SZRT), Jia-Wei-Xiao-Yao-San (JWXYS), He-Huan-Pi (HHP; Cortex Albizziae; Albizia julibrissin Durazz.), and Suan-Zao-Ren (SZR; Semen Zizyphi Spinosae; Ziziphus jujuba Mill.) were important CHMs for patients with sleep disorders in Taiwan. CONCLUSIONS: A comprehensive list of herbal medicines may be useful for the clinical treatment of patients with sleep disorders, and for future scientific investigations into the prevention of dementia in these patients.

Hierarchical U-shape Attention Network for Salient Object Detection.

Salient object detection aims at locating the most conspicuous objects in natural images, which usually acts as a very important pre-processing procedure in many computer vision tasks. In this paper, we propose a simple yet effective Hierarchical U-shape Attention Network (HUAN) to learn a robust mapping function for salient object detection. Firstly, a novel attention mechanism is formulated to improve the well-known U-shape network [1], in which the memory consumption can be extensively reduced and the mask quality can be significantly improved by the resulting U-shape Attention Network (UAN). Secondly, a novel hierarchical structure is constructed to well bridge the low-level and high-level feature representations between different UANs, in which both the intra-network and inter-network connections are considered to explore the salient patterns from a local to global view. Thirdly, a novel Mask Fusion Network (MFN) is designed to fuse the intermediate prediction results, so as to generate a salient mask which is in higher-quality than any of those inputs. Our HUAN can be trained together with any backbone network in an end-to-end manner, and high-quality masks can be finally learned to represent the salient objects. Extensive experimental results on several benchmark datasets show that our method significantly outperforms most of the state-of-the-art approaches.

Anti-inflammatory effects of powdered product of Bu Yang Huan Wu decoction: Possible role in protecting against Transient Focal Cerebral Ischemia.

Bu Yang Huan Wu decoction (BYHW) is a traditional Chinese medicine (TCM) that consists of several herbs and has been used in patients with ischemic stroke for centuries. Although powdered formula of BYHW has widely been prescribed in clinic nowadays, evidence-based effectiveness and mechanism of action of BYHW powdered product in stroke remain to be characterized. Adult male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 90 min followed by reperfusion for 24 h (ischemia/reperfusion; I/R) or sham surgery. After I/R, the rats were then given low dose (0.5 g/kg) and high dose (2.5 g/kg) of BYHW or vehicle by oral gavage twice a day for seven consecutive days. The results showed that I/R induced obvious cerebral infarction and neurobehavioral defects, in parallel with histological aberrations and extensive signaling of proinflammatory cytokines, including tumor necrosis factor (TNF-α) and interleukin-6 (IL-6), in the stroke model. Post-I/R treatment with BYHW powdered product significantly reduced the infarct area and ameliorated neurofunctional defects in a dose-dependent manner. The dose dependence was associated with TNF-α downregulation and interleukin-10 (IL-10) induction. In summary, the present findings demonstrated that BYHW powdered product exhibited therapeutic efficacy for experimental stroke and a higher dose treatment may strengthen the effectiveness via inflammatory modulation.

Development of an in situ diagnostic system for mapping the deposition distribution on plasma facing components of the HL-2M tokamak.

The assessment of material deposition and fuel retention on Plasma Facing Components (PFCs) is of primary importance for the steady-state operations of future fusion devices. In this paper, an in situ diagnostic for mapping the deposition distribution (IMap) on a wide area of PFCs for HL-2M (Huan Liu Qi-2 Modification) is developed. The design, fabrication, integration, and lab test of the IMap have been implemented. This system is built with the laser-induced breakdown spectroscopy technique which is an in situ diagnostic technique to determine the constituents and the depth profile of deposition compositions on PFCs. With a molybdenum reflection mirror inside the chamber and its manipulator, the IMap system can scan from the inner wall across the lower divertor to the outer middle plane. The system can be remotely controlled, and its optical lenses, mirrors, and fibers can be adjusted automatically when scanning over the PFCs. Therefore, the wall properties over a wide area of the vessel can be measured. All elements with the emission lines in the range of 380-850 nm can be analyzed, and the isotope species H and D can also be identified clearly with this diagnostic. Moreover, the depth profiles of the deposited materials can be determined, and the fuel retention on PFCs can be evaluated in situ. This gives a clear picture of the deposition and retention over the wall of HL-2M.

Correction to: Prof. Huan-Yong Chen: a leading botanist and taxonomist, one of the pioneers and founders of modern plant taxonomy in China.

In the original publication, there are some incorrect information.

Correction to: Prof. Huan-Yong Chen: a leading botanist and taxonomist, one of the pioneers and founders of modern plant taxonomy in China

In the original publication, there are some incorrect information.

Strong convergence theorems for coordinatewise negatively associated random vectors in Hilbert space.

In this work, some strong convergence theorems are established for weighted sums of coordinatewise negatively associated random vectors in Hilbert spaces. The results obtained in this paper improve and extend the corresponding ones of Huan et al. (Acta Math. Hung. 144(1):132-149, 2014) as well as correct and improve the corresponding one of Ko (J. Inequal. Appl. 2017:290, 2017).

Eupafolin and Ethyl Acetate Fraction of Kalanchoe gracilis Stem Extract Show Potent Antiviral Activities against Enterovirus 71 and Coxsackievirus A16.

Enterovirus 71 (EV71) and coxsackievirus A16 (CoxA16) are main pathogens of hand-foot-and-mouth disease, occasionally causing aseptic meningitis and encephalitis in tropical and subtropical regions. Kalanchoe gracilis, Da-Huan-Hun, is a Chinese folk medicine for treating pain and inflammation, exhibiting antioxidant and anti-inflammatory activities. Our prior report (2012) cited K. gracilis leaf extract as moderately active against EV71 and CoxA16. This study further rates antienteroviral potential of K. gracilis stem (KGS) extract to identify potent antiviral fractions and components. The extract moderately inhibits viral cytopathicity and virus yield, as well as in vitro replication of EV71 (IC50 = 75.18 µ g/mL) and CoxA16 (IC50 = 81.41 µ g/mL). Ethyl acetate (EA) fraction of KGS extract showed greater antiviral activity than that of n-butanol or aqueous fraction: IC50 values of 4.21 µ g/mL against EV71 and 9.08 µ g/mL against CoxA16. HPLC analysis, UV-Vis absorption spectroscopy, and plaque reduction assay indicate that eupafolin is a vital component of EA fraction showing potent activity against EV71 (IC50 = 1.39 µ M) and CoxA16 (IC50 = 5.24 µ M). Eupafolin specifically lessened virus-induced upregulation of IL-6 and RANTES by inhibiting virus-induced ERK1/2, AP-1, and STAT3 signals. Anti-enteroviral potency of KGS EA fraction and eupafolin shows the clinical potential against EV71 and CoxA16 infection.

Deciphering the neuroprotective mechanisms of Bu-yang Huan-wu decoction by an integrative neurofunctional and genomic approach in ischemic stroke mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Bu-yang Huan-wu decoction (BHD) is a famous traditional Chinese medicine formula that has been used clinically in Asia to treat stroke-induced disability for centuries, but the underlying neuroprotective mechanisms are not fully understood. AIM OF THE STUDY: In this study, we aim to investigate the mechanisms of action using an integrative neurofunctional and broad genomics approach. MATERIALS AND METHODS: Male ICR mice were subjected to an acute ischemic stroke by inducing a middle cerebral ischemic/reperfusion (CI/R) injury. To examine whether BHD could extend the lifespan of mice with a stroke, we used oral administration of BHD (0.5 and 1.0g/kg) twice daily starting from 2h after ischemia and compared this with vehicle control treatments, recombinant tissue-type plasminogen activator (rt-PA, 10mg/kg, i.v.), and MK-801 (0.2mg/kg, i.p.). An integrative neurofunctional and genomic approach was performed to elucidate the underlying molecular mechanisms of BHD. RESULTS: More than 80% of the mice died within 2 days after stroke induction in the vehicle control treatment group. However, the survival rates and life-spans of mice treated with BHD, rt-PA and MK-801 were significantly enhanced as compared to the vehicle-treated CI/R group in all three cases. Mice treated with BHD (1.0g/kg) showed the greatest protective effect across all groups. BHD successfully restored brain function, ameliorated the cerebral infarction, and significantly improved the neurological deficits of the mice with a stroke. BHD also reduced inflammation, oxidative stress, and apoptosis, as well as improved neurogenesis. The molecular impacts of BHD were assessed by genome-wide transcriptome analysis using brains from the CI/R mice. The results showed a total of 377 ischemia-induced probe-sets that were significantly influenced by BHD including 93 probe-sets that were commonly more abundant in BHD-treated and sham mice, and another 284 ischemia-induced probe sets that were suppressed by BHD. Mining the functional modules and genetic networks of these 377 genes revealed a significant upregulation of neuroprotective genes associated with neurogenesis (6 genes) and nervous system development (9 genes), and a significant down-regulation of destructive genes associated with the induction of inflammation (14 genes), apoptosis (15 genes), angiogenesis (11 genes) and blood coagulation (7 genes) by BHD. CONCLUSIONS: Our results suggested that BHD is able to protect mice against stroke and extend lifespan primarily through a significant down-regulation of genes involved in inflammation, apoptosis, angiogenesis and blood coagulation, as well as an up-regulation of genes mediating neurogenesis and nervous system development. The changes in expression after treatment with BHD are beneficial after ischemic stroke.

[Analysis of dynamic change of huperzine A content in Huperzia serrata].

A precise and selective reversed phase high-performance liquid chromatographic method (HPLC) was used to quantify the levels of huperzine A in samples of three Huperzia serrata populations with a total of 73 individuals located in Zhejiang, Guangxi, Chongqing, respectively, as well as in one-to-one samples of these 73 individuals introduced in same site after one year. Huperzine A content variation both among and within populations, and the dynamic change of this alkaloid occurring in same population after one year introduction, were analyzed using SPSS 13.0 software (Coefficient of variation, One-way ANOVA analysis, Paired-samples T tests). The results indicated that huperzine A content varied significantly by geographical locations, especially change with longitude, i. e., the order of the huperzine A content was CQ population > GX population > ZJ population. The coefficients of variation (CV) were as follows: 0.36 (CQ), 0.44 (GX) and 0.40 (ZJ). This indicated that there was plentiful diversity concerned with huperzine A content among individuals within population. Moreover, this high diversity was still maintained after one year introduction. ANOVA analysis showed that there was significant difference among populations in huperzine A content. Finally, the significant change of huperzine A content was not observed in all three populations after one year introduction. The results presented in this study could provide evidence that the huperzine A content variation of H. serrata is the results of an interaction between genes and the environment, by comparison, is mainly controlled by genetic factor.

C-fos expression during electroacupuncture analgesia in rats--an immunohistochemical study.

Although the central mechanisms of electroacupuncture analgesia (EAA) have been investigated, a systematic study for the involvement of neuronal populations of central nervous system (CNS) in EAA has not been well undertaken, largely due to the difficulty in tracing the neuronal pathways by traditional techniques. Recently developed c-fos expression examination by immunohistochemical method with Ab-1 antisera might be used for this purpose as a useful marker for neuronal activity in CNS. In this study, tail flick latency (TFL) was tested as an index of pain threshold in conscious rats. After unilateral electroacupuncture was applied at 'Zuan-san-li' and 'Huan-tiao', the TFL was significantly prolonged. To explore the possible involvement of certain neuronal groups of central nervous system in EAA, we examined the EAA accompanied c-fos expression throughout the neuraxis, and a lot of specific c-fos protein labelled neurons were found in lumbar spinal cord (laminae I and II), nucleus raphe magnus, nucleus raphe dorsalis, substantia grisea centralis, nucleus habenulae lateralis, nucleus habenulae medialis, nucleus medialis thalami, nucleus lateralis hypothalami, nucleus supramamillaris, nucleus supraopticus, nucleus arcuatus, nucleus preopticus medialis, nucleus amygdala, nucleus tractus diagonalis, etc. No obvious c-fos expression was shown in these areas on control rats. These results strongly suggested that the functional activation of above-mentioned nuclei by electroacupuncture was underlied in EAA action.