Lycopodium Alkaloids from Huperzia serrata and Their Anti-acetylcholinesterase Activities.

One new fawcettimine-type alkaloid (1), one new miscellaneous-type alkaloid (2), four new lycodine-type alkaloids (3-6), and eight known ones (7-14) were isolated from the whole plants of Huperzia serrata. Their structures and absolute configurations were elucidated based on spectroscopic data, X-ray diffraction, ECD calculation and Mosher's method. Compound 1 was a rare C18 N2 -type Lycopodium alkaloid, possessing serratinine skeleton with an amide side chain in C-5. The absolute configuration of the 18-OH of compounds 4-6 were first determined by Mosher's method. Moreover, compounds 1-14 were assayed anti-acetylcholinesterase effect in vitro, and compound 7 showed significant anti-acetylcholinesterase activity with an IC50 value of 16.18±1.64 µM.

Excessive Treadmill Training Produces different Cardiac-related MicroRNA Profiles in the Left and Right Ventricles in Mice.

High-volume training followed by inadequate recovery may cause overtraining. This process may undermine the protective effect of regular exercise on the cardiovascular system and may increase the risk of pathological cardiac remodelling. We evaluated whether chronic overtraining changes cardiac-related microRNA profiles in the left and right ventricles. C57BL/6 mice were divided into the control, normal training, and overtrained by running without inclination, uphill running or downhill running groups. After an 8-week treadmill training protocol, the incremental load test and training volume results showed that the model had been successfully established. The qRT-PCR results showed increased cardiac miR-1, miR-133a, miR-133b, miR-206, miR-208b and miR-499 levels in the left ventricle of the downhill running group compared with the left ventricle of the control group. Similarly, compared with the control group, the downhill running induced increased expression of miR-21, miR-17-3p, and miR-29b in the left ventricle. Unlike the changes in the left ventricle, no difference in the expression of the tested miRNAs was observed in the right ventricle. Briefly, our results indicated that overtraining generally affects key miRNAs in the left ventricle (rather than the right ventricle) and that changes in individual miRNAs may cause either adaptive or maladaptive remodelling with overtraining.

[Characteristics of Sleep Electroencephalographic Power in Chronic Insomnia Patients].

OBJECTIVE: To study the sleep electroencephalogram (EEG) power features of patients with chronic insomnia. METHODS: Retrospective analysis was performed with patients who met the ICD-10 diagnostic criteria for chronic insomnia, using polysomnography (PSG) to examine the overnight sleep EEG. The sleep architectures and relative EEG power across five frequency bands during overnight sleep were compared to study the differences between the insomnia and control groups. Furthermore, the correlation between EEG power and various PSG measures was also analyzed. RESULTS: Forty-five subjects were enrolled in the study, including 25 chronic insomniacs (18 females, aged [36.2±10.7] years) and 20 controls (18 females, aged [36.1±7.6] years). Compared to those of the control group, insomnia patients had significantly lower value of delta power ([38.0±6.1] vs. [43.2±5.8], P<0.05) in the NREM1 stage, and increased value of beta power during total NREM, NREM1 and NREM2 (NREM sleep [5.4±2.3] vs. [3.8±1.4], NREM1 [11.3±3.5] vs. [8.7±2.8], and NREM2 [5.7±2.3] vs. [4.4±1.4], all P<0.05). For correlation analyses, in the insomnia group, a significantly positive correlation was found between the delta value during NREM sleep and the duration of NREM3 sleep ( r=0.527). The beta value during NREM sleep was found to be negatively correlated to the duration of NREM3 sleep ( r=－0.767). A positive correlation was found between the beta value during NREM sleep and the duration of NREM1 and NREM2 sleep ( r=0.486 and 0.589, respectively). CONCLUSION: The results suggest that patients with chronic insomnia have decreased low-frequency EEG power, but increased high-frequency EEG power during NREM sleep. The findings indicate that cortex arousal level is elevated in chronic insomniacs during NREM sleep.

Construction and immune efficacy of recombinant Lactobacillus casei strains expressing Malt from Aeromonas veronii.

Aeromonas veronii is an important zoonotic pathogen that causes significant economic losses in the aquaculture industry. The use of probiotics in aquaculture is a practical alternative to antibiotics to promote animal health and aid in disease prevention. In the present study, we aimed to construct a recombinant Lactobacillus casei(surface-displayed or secretory) strain containing Malt from A. veronii TH0426 and assess its potential as an oral vaccine. A 1314-bp Malt gene fragment was successfully amplified and cloned into a prokaryotic protein expression system. Protein expression in resulting recombinant strains Lc-MCS-Malt (surface-displayed) and Lc-pPG-Malt (secretory) was then verified by Western blotting and indirect immunofluorescence. A single band was observed on the Western blots, with the molecular weight of the corresponding protein shown to be 48 kDa. Furthermore, a fluorescent signal for Lc-MCS-Malt was observed by fluorescence microscopy. At 0, 7, 16, 25, and 34 days post-immunization, tissue and blood samples were collected from common carp orally administered with the recombinant L. casei strains for immune-related index analyses. Treatment of common carp with the recombinant vaccine candidate stimulated high serum or skin mucus specific antibody titers and induced a higher lysozyme, ACP, SOD activity, while fish fed with Lc-pPG or PBS had no detectable immobilizing immune responses. Expression of IL-10, IL-1ß, TNF-α, and IFN-γ genes in the group immunized with recombinant L. casei were significantly (P < 0.05) up regulated as compared with control groups, indicating that inflammatory response and cell immune response were triggered. Results also showed that recombinant L. casei could stimulate the mucosa through colonization of the intestine, resulting in increased transcription of IL-10, IL-1ß, TNF-α, and IFN-γ. Immunity and colonization assays also showed that after 34 days of fasting, recombinant L. casei were still present in the intestines of the immunized fish. Common carp that received Lc-MCS-Malt(53.3%) and Lc-pPG-Malt (46.7%) exhibited higher survival rates than the controls after challenge with the pathogen A. veronii. Our findings suggested that recombinant L. casei can adequately protect fish and improve immunity, providing a theoretical basis for the future development of an oral Lactobacillus vaccine for use in aquaculture.

An effective live attenuated vaccine against Aeromonas veronii infection in the loach (Misgurnus anguillicaudatus).

Aeromonas veronii is a major pathogenic bacterium in humans and animals. When it causes outbreaks, there are enormous economic losses to the aquaculture industry. An effective live attenuated vaccine strain, ΔhisJ, was obtained in our previous studies by gene knockout in Aeromonas veronii TH0426 using the suicide vector pRE112. Here, we evaluated whether the live attenuated vaccine ΔhisJ was suitable for prevention of Aeromonas veronii infection by injection and immersion in loaches. Compared with that of the TH0426 wild-type strain, the virulence of the live vaccine was significantly weakened. Vaccine safety assessment results also indicated that 1 × 107 CFU/mL live vaccine was safe and did not induce clinical symptoms or obvious pathological changes. Additionally, after challenging loaches with Aeromonas veronii TH0426, the relative percent survival of the IN3 injection group was 65.66%, and that of the IM group was 50.78%. Our data show that the live attenuated vaccine ΔhisJ can improve the immune protection rate of loaches. Furthermore, increased enzyme activity parameters (SOD, LZM, ACP, and AKP) in the skin mucus, increased enzyme activity parameters (SOD, LZM, ACP, AKP, and GPx) in the serum, increased specific IgM antibodies and cytokine IL-1ß contents in the serum, and increased cytokine (IL-15, pIgR, IL-1ß, and TNF-α) expression in the liver and spleen were observed. These data are the first to indicate that the live attenuated vaccine ΔhisJ is suitable for the development of a safe and effective vaccine against Aeromonas veronii infection in loach aquaculture.

Immunogenicity of extracellular products from an inactivated vaccine against Aeromonas veronii TH0426 in koi, Cyprinus carpio.

Aeromonas veronii is a type of human-livestock-aquatic animal pathogen; it is widely found in nature and causes many deaths among aquatic animals. Extracellular products (ECPs) are secreted by the pathogen during growth and reproduction. These products are considered effective protective antigens that can induce the host to produce an immune response. In this study, the ECPs of A.veronii TH0426 were prepared by ultrafiltration, and then the pathogenicity and enzymatic activity of the ECPs were determined. All the groups were injected intraperitoneally, as follows: group one: ECP protein with an equal volume of Freund's adjuvant; group two: ECPs and formalin-killed cells (FKC) of A.veronii combined with an equal volume of Freund's adjuvant (FKC + ECPs); group three: formalin-killed cells (FKC) of A.veronii combined with an equal volume of Freund's adjuvant (FKC); and, group four: sterile PBS as the control group. The expression levels of IgM, IL-1ß, and TNF-α and the lysozyme activity in blood were examined at 7, 14, and 21 days after the immunizations. The results show that the ECPs can produce protease, lipase, amylase and hemolyase, and there was no lecithinase, urease, or gelatinase activity. The results indicate that the ECPs were clearly pathogenic to koi fish, and the LD50 dose was 391.6 µg/fish. Throughout this study, the RPS of the three experimental groups were 75%, 50%, and 70%. This study indicates that the ECPs of A.veronii can effectively enhance the ability of kio fish to resist bacterial invasion.

A retrospective comparison of the modified tension band technique and the parallel titanium cannulated lag screw technique in transverse patella fracture.

OBJECTIVE: To compare efficacy between the modified tension band technique and the parallel titanium cannulated lag screw technique for the transverse patella fracture. METHODS: Seventy-two patients were retrospectively analyzed aged 22 to 79 years (mean, 55.6 years) with transverse patella fractures, among whom 37 patients underwent the modified tension band and 35 patients received the titanium cannulated lag screw. Patients were followed up for 1-3 years. We analyzed the difference of operation time, complications, fracture reduction, fracture healing time, and the Iowa score for knee function between both groups. RESULTS: In modified tension band group, five patients had skin irritation and seven suffered wire migration, two of whom required a second operation. In comparison, there were no complications in the titanium cannulated lag screw group, which also had a higher fracture reduction rate and less operation time. CONCLUSION: The parallel titanium cannulated lag screw technique has superior results and should be considered as an alternative method to treat transverse patella fracture.

Role of neuronal nitric oxide synthase in the cardiac ischemia reperfusion in mice.

Several studies have demonstrated the role of endothelial and inducible nitric oxide synthase in cardiac ischemia reperfusion(IR). However, the role of neuronal nitric oxide synthase (nNOS) in IR is still controversial. The present study was designed to explore the possible involvement of nNOS in cardiac IR. nNOS-/- knockout (KO) and wild type C57 (WT) mice were subjected to 45 min of ischemia by left descending branch of coronary artery ligation followed by 3 h reperfusion, which plasma was collected for creatine kinase (CK) and lactate dehydrogenase (LDH) measurements, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining and measurements of activities of caspase-3, -8, -9, phospho-p38, -ERK, -JNK mitogen-activated protein kinase (MAPK) and phospho-nNOS, phospho-eNOS and iNOS. IR induced cardiac tissue apoptosis by increases of TUNEL staining and activities of caspase-3, -8, and -9, accompanied with increase of CK and LDH concentration and phosphorylation of p38, ERK and JNK MAPK and phospho-nNOS, phospho-eNOS and iNOS in both mouse strains. However, IR induced increases of TUNEL staining and activities of caspase-3, -8 and -9, and CK and LDH concentrations and activation of p38 MAPK were markedly lower in KO mice compared with WT mice. But the phosphorylation of eNOS was significantly higher compared with WT IR group (P < 0.05). The data obtained suggest that nNOS exacerbates IR-induced injury maybe involving p38 MAPK activation.

Modulation of oxidized low-density lipoprotein-affected macrophage efferocytosis by mitochondrial calcium uniporter in a murine model.

OBJECTIVE: Efferocytosis dysfunction contributes to the progression and rupture of atherosclerotic plaques. Efferocytosis is crucially modulated by intracytoplasmic Ca2+, and mitochondrial calcium uniporter (MCU) complex proteins serve as key channels for regulating Ca2+ concentration. Therefore, it was speculated that MCU may affect the development of atherosclerosis (AS) by regulating efferocytosis. In the present study, we aimed to investigate whether MCU could affect foam cell formation by regulating efferocytosis. METHODS: We stimulated primary macrophages (Møs) using oxidized low-density lipoprotein (ox-LDL) to mimic the atherosclerotic microenvironment and treated them with Ru360, an MCU-specific inhibitor, and UNC1062, an inhibitor of efferocytosis. Additionally, we conducted double staining to determine the Mø efferocytosis rate. We measured the expression of MCU complexes and efferocytosis-associated proteins using western blotting (WB) and real-time quantitative polymerase chain reaction (RT-qPCR), respectively. In addition, we separately detected the Ca2+ level in the cytoplasm and mitochondria (MT) using Fluo-4 AM and Rhod-2 methods. We separately determined the reactive oxygen species (ROS) level in cytoplasm and MT using dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probing method and Mito-SOXTM superoxide indicator staining. Additionally, we conducted the enzyme-linked immunosorbent assay (ELISA) to detect the production of interleukin-6 (IL-6), interleukin-18 (IL-18), interleukin-1ß (IL-1ß), and tumor necrosis factor-alpha (TNF-α). Oil Red O staining was performed to measure cytoplasmic lipid levels. RESULTS: Ru360 attenuated ox-LDL-induced efferocytosis dysfunction, and attenuated the upregulation of MCU and MCUR1 induced by ox-LDL, and meanwhile attenuated the downregulation of MCUb induced by ox-LDL. Ru360 attenuated the decrease of intracytoplasmic Ca2+ concentration induced by ox- LDL, Ru360 also attenuated the ROS production induced by ox- LDL, attenuated the release of IL-6, IL-18, IL-1ß, and TNF-α induced by ox- LDL, and attenuated the increase of intracytoplasmic lipid content induced by ox-LDL. UNC1062 attenuated the effects of Ru360 in reducing inflammatory cytokines and intracytoplasmic lipid content. CONCLUSIONS: In this study, we found that MCU inhibition modulated intracytoplasmic Ca2+ concentration, improved impaired Mø efferocytosis, and reduced ROS generation. Macrophage efferocytosis removed apoptotic cells and prevented the release of inflammatory factor and foam cell formation, and this can be a potential new therapeutic target for alleviating atherosclerosis.

Antibiotic synergist OM19r reverses aminoglycoside resistance in multidrug-resistant Escherichia coli.

Introduction: The continued emergence and spread of multidrug-resistant (MDR) bacterial pathogens require a new strategy to improve the efficacy of existing antibiotics. Proline-rich antimicrobial peptides (PrAMPs) could also be used as antibacterial synergists due to their unique mechanism of action. Methods: Utilizing a series of experiments on membrane permeability, In vitro protein synthesis, In vitro transcription and mRNA translation, to further elucidate the synergistic mechanism of OM19r combined with gentamicin. Results: A proline-rich antimicrobial peptide OM19r was identified in this study and its efficacy against Escherichia coli B2 (E. coli B2) was evaluated on multiple aspects. OM19r increased antibacterial activity of gentamicin against multidrug-resistance E. coli B2 by 64 folds, when used in combination with aminoglycoside antibiotics. Mechanistically, OM19r induced change of inner membrane permeability and inhibited translational elongation of protein synthesis by entering to E. coli B2 via intimal transporter SbmA. OM19r also facilitated the accumulation of intracellular reactive oxygen species (ROS). In animal models, OM19r significantly improved the efficacy of gentamicin against E. coli B2. Discussion: Our study reveals that OM19r combined with GEN had a strong synergistic inhibitory effect against multi-drug resistant E. coli B2. OM19r and GEN inhibited translation elongation and initiation, respectively, and ultimately affected the normal protein synthesis of bacteria. These findings provide a potential therapeutic option against multidrug-resistant E. coli.

Lipopolysaccharide Alters the m6A Epitranscriptomic Tagging of RNAs in Cardiac Tissue.

N6-methyladenosine (m6A) modification plays important roles in the pathology of a variety of diseases. However, the roles of m6A modification in sepsis-induced myocardial dysfunction are not well defined. Rats were divided into control and lipopolysaccharide (LPS)-induced sepsis group. Global m6A levels of left ventricle tissue were measured by LC-MS/MS, and transcriptome-wide m6A modifications were profiled using epitranscriptomic microarrays (mRNAs and lncRNAs). Bioinformatics analysis was conducted to understand the functional implications of m6A modifications during sepsis. Methylated lncRNAs and mRNAs were measured by m6A single-base site qPCR. The global m6A levels in left ventricle tissue were significantly decreased in the LPS group. While 27 transcripts (23 mRNAs and four lncRNAs) were hypermethylated, 46 transcripts (39 mRNAs and 7 lncRNAs) were hypomethylated in the LPS group. The mRNA expression of writers and readers was significantly decreased in the LPS group. The m6A modification of Clec1b, Stk38l and Tnfrsf26 was associated with platelet activation and apoptotic pathways. Moreover, the decrease in m6A modification of lncRNA XR_346,771 may be related to cation import in cardiac tissue. Our data provide novel information regarding changes to m6A modifications in cardiac tissue during sepsis, and m6A modifications might be promising therapeutic targets.

Functional analysis of hisJ in Aeromonas veronii reveals a key role in virulence.

Aeromonas veronii is an important aquatic zoonotic pathogen in humans and animals. In recent years, extracellular proteins from bacteria have been found to be the major pathogenic factors for aquatic animals. The aim of this study was to systematically analyze the extracellular proteins of nine sources of A. veronii and the effects of hisJ on virulence. We screened only the common proteins from nine different sources of A. veronii by liquid chromatography-tandem mass spectrometry and identified the gene hisJ. We then constructed ΔhisJ (deleted) and C-hisJ (complemented) variants of A. veronii TH0426 to assess the biological function of hisJ. While the ΔhisJ strain did not show altered growth (P > 0.05), we observed that it had reduced colony formation and biofilm formation and reduced adhesion to and invasion of epithelioma papulosum cyprini cells by 2.0-, 1.9-, and 10.8-fold, respectively. Additionally, infection experiments on zebrafish and mouse infection experiments showed that the virulence of the ΔhisJ strain was decreased by 865-fold (P < 0.001) compared with the wild-type strain; virulence of the complemented C-hisJ strain was reduced only 2.8-fold. Furthermore, in the context of hisJ deletion, flagella of A. veronii TH0426 were easily detached and the expression of virulence genes was downregulated. A persistence test (of bacterial colonies in crucian carp) showed that the number of bacteria in the immune organs of the ΔhisJ-infected group was lower than that in the wild-type-infected group. Overall, these results show that hisJ affects flagellar shedding, virulence, biofilm formation, adhesion, and invasion of A. veronii TH0426, and that hisJ is closely associated with virulence and plays a crucial role in its pathogenicity of A. veronii TH0426.

Primary malignant gastrointestinal neuroectodermal tumor occurring in the ileum with intra-abdominal granulomatous nodules: A case report and review of the literature.

Malignant gastrointestinal neuroectodermal tumors (GNETs) are rare aggressive malignant neoplasms that exclusively occur within the wall of the gastrointestinal tract. The GNET was first described as an 'osteoclast-rich tumor of the gastrointestinal tract with features resembling clear cell sarcoma (CCS) of soft parts' in 2003. Although the GNET shares certain histological features with CCS, it is characterized by a lack of melanocytic differentiation and the presence of non-tumoral osteoclast-like giant cells (OLGCs). The present study reports a case of a GNET of the ileum with intra-abdominal granulomatous nodules, an uncommon accompanying finding, and summarizes the current literature. A 30-year-old woman presented with the symptoms of intestinal obstruction, and a mass was found within the ileum wall. Multiple grey-white nodules were found adhering to the omentum and serosa of the ileum. Histologically, the tumor was located in the muscularis propria and infiltrated the mucosa and the serosa. Tumor cells presented with oval or polygonal nuclei and prominent nucleoli, and were predominantly arranged in nested and pseudopapillary patterns, with the presence of cluster of differentiation (CD)68-positive, scattered OLGC. Immunohistochemically, it was determined that the tumor cells expressed Vimentin, CD56, S-100 and transcription factor SOX-10, while being negative for pan-cytokeratin, cytokeratin (CK)7, CK20, synaptophysin, chromogranin-A, CD117, anoctamin-1, CD34, human melanoma black-45, Melan-A, smooth muscle actin, CD3 and CD20 expression. Ewing sarcoma breakpoint region 1 gene rearrangement was identified by fluorescence in situ hybridization analysis. Ultrastructurally, no typical melanosomes were identified. In addition, the intra-abdominal grey-white nodules were microscopically identified as chronic granulomatous inflammation. The patient received four cycles of adjuvant chemotherapy following routine tumor resection. Due to its rarity and histological similarity with other neoplasms, unfamiliarity with the features of GNETs by surgical pathologists can easily lead to a misdiagnosis. Therefore, comprehensive assessments, including morphology and ancillary studies, are required for an accurate diagnosis of GNET.

Overexpression of MCM6 predicts poor survival in patients with glioma.

Minichromosome maintenance proteins (MCMs) play an essential role in DNA replication and other cellular activities. However, their expression levels and clinical value in glioma are unclear. In the present study, we analyzed the relationship between MCM mRNA expression and clinical parameters in 325 gliomas and found that MCM6 presented high expression and was associated with poor survival. Immunohistochemistry analysis of an independent data set of 423 glioma tissues confirmed the overexpression of MCM6 protein, especially in glioblastomas with shorter overall survival. Importantly, a combination of MCM6 overexpression with IDH1 mutation further improved the prediction of the prognosis of glioblastomas. Patients with IDH1 mutation and low MCM6 expression exhibited the longest survival, whereas those with high MCM6 expression and wild-type IDH1 showed the shortest. Collectively, our observation indicates that MCM6 is a novel potential biomarker for predicting poor prognosis of the patients with glioma.

Phosphorylated Hsp27 is mutually exclusive with ATRX loss and the IDH1R132H mutation and may predict better prognosis among glioblastomas without the IDH1 mutation and ATRX loss.

AIM: To identify biomarkers for accurate classification of glioma. PATIENTS AND METHODS: We evaluated the heat shock protein 27 (Hsp27), phosphorylated Hsp27 (p-Hsp27), ATRX and IDH1R132Hproteins using immunohistochemistry in 421 glioma tissues. The χ2 test was used to assess the relationship between molecular alterations and clinico-pathological parameters. Kaplan-Meier survival curves were constructed, and differences were detected by the log-rank test. RESULTS: We found that Hsp27 and p-Hsp27 were mainly expressed in aggressive astrocytic gliomas. However, neither Hsp27 nor p-Hsp27 expression was related to survival time for any grade of glioma. Interestingly, p-Hsp27 was mutually exclusive with ATRX loss (ATRX-) and the IDH1R132H mutation, except for one case of anaplastic astrocytoma. We classified glioblastomas (GBMs) into three subtypes: ATRX-/IDH1R132H, high p-Hsp27 expression (p-Hsp27+) and none of these three markers. ATRX-/IDH1R132Hshowed the longest median survival (19.6 months). The prognostic difference between p-Hsp27+ and none of these three markers was significant (15.0 vs 13.1 months, P=0.045). Moreover, p-Hsp27+ predicted better sensitivity for standard therapy among GBMs without the IDH1 mutation and ATRX loss (26.3 vs 15.5 months, P=0.008). CONCLUSION: p-Hsp27 is a novel biomarker of glioma and might have important clinical value for further classification of patients with wild-type IDH1 and normal ATRX expression, for evaluating prognosis and for guidance for adjuvant therapy.

Comparison of pharmacokinetic profiles of Terminalia phenolics after intragastric administration of the aqueous extracts of the fruit of Terminalia chebula and a Mongolian compound medicine-Gurigumu-7.

ETHNOPHARMACOLOGICAL RELEVANCE: The dried fruit of Terminalia chebula (fructus chebulae) is an important Traditional Medicine used for intestinal and hepatic detoxification. Gurigumu-7 which is made of fructus chebulae and 6 other traditional medicines is one of the most frequently used compound Mongolian and Tibet medicines for liver diseases. Terminalia phenolics are considered as the bioactive constituents of fructus chebulae and consequently of Gurigumu-7. AIM OF THE STUDY: To compare the pharmacokinetic profiles of Terminalia phenolics after intragastric administration of the aqueous extracts of fructus chebulae and Gurigumu-7 and to evaluate the possible influence of intestinal bacterial metabolism on these pharmacokinetic profiles. MATERIALS AND METHODS: An ultra performance liquid chromatography with triple quadrupole mass spectrometry method was established and validated for simultaneously determining the pharmacokinetic profiles of seven Terminalia phenolics after intragastric administration of pure compounds, fructus chebulae extract, and Gurigumu-7 extract. In vitro rat fecal lysates experiments were carried out to explore the metabolic discrepancy between fructus chebulae and Gurigumu-7. RESULTS: Seven Terminalia phenolics were detected in rat plasma after intragastric administration of the aqueous extracts of fructus chebulae and Gurigumu-7. Administration of Gurigumu-7 could promote the absorption and increase the Cmax and AUC values of these phenolic constituents compared to fructus chebulae administration. The fecal lysates studies showed that the Terminalia phenolics in Gurigumu-7 were less rapidly bio-transformed than those in fructus chebulae. This may be a contributing factor to the pharmacokinetic discrepancy between the phenolics in fructus chebulae and Gurigumu-7. CONCLUSION: Administration of Gurigumu-7 could increase the absorption of Terminalia phenolics through slowing down the intestinal bacteria metabolism. These results provide, in part, an in vivo rationale for the formulation of the traditional Mongolia / Tibet medicine, Gurigumu-7.

[Textual research on the Wu zhi fang (Prescriptions of Five Hemorrhoids) of Ding Zhai, a lay Buddhist].

The book Wu zhi fang (Prescriptions of Five Hemorrhoids), included in the Bibliography of the Song Annals was claimed by later scholars as a book written by Dingzhai, the lay Buddhist. Parts of its contents are cited in Wei Xian's Wei shi jia cang fang (Collections of Prescriptions of the Wei Family). By the preface of the latter book, the prescriptions of the Wu zhi fang were derived from Li Yong-he, whose son passed these prescriptions to Ma Xing-si, who, in turn, gave them to Wei Xian's father Wei Xiong-meng. Wei Xiong-meng was familiar with a calligrapher of the Southern Song Dynasty Shan Wei, nicknamed Dingzhai, the lay Buddhist, who wrote the autobiography for Wei Xiong-meng. In addition to those collected in the Wei shi jia cang fang, there are also "Li Fangyu's Prescriptions for Five Hemorrhoids Secretly Handed Down" collected in the Mi chuan wai ke fang (Prescriptions for External Diseases Secretly Handed Down) of the Ming Dynasty which are also Li Yong-he's prescriptions for hemorrhoids, outnumbering those collected by the Wei shi jia cang fang.

[Approaches to acquire medical prescriptions by the Song intellectuals].

In order to treat disease of oneself or other people, the Song intellectuals were eager to collect medical recipes or compiled medical formularies. Their main approaches in this regard included conversation with medical practitioners, mutual communication among themselves, and reading medical texts. Since the effectiveness of the recipes was emphasized through the first two approaches, the approach of reading medical texts appeared to be insignificant. Even if this last approach was selected, they tended to read those texts with evidences showing its effectiveness of the recipes carried in the texts.

[The tension between history and medicine in TCM historiography].

Before subject classification was introduced from the western world Traditional Chinese Medicine (TCM) had the background of Chinese traditional culture, and therefore the features of both medicine and historiography. After the introduction of subject classification, TCM was classified into medicine which is a science category and TCM history was classified into the historiography category. From then on, in the context of subject classification, the nature of TCM became more and more medical while less and less historic. As the subject classification of TCM has not been completed, its history needs retrospective study retrospective study needs to be done to its history. Focusing on TCM subject classification and on reality, TCM historiography usually highlights the medical part. In the process of TCM subject classification, the historic mode of academic development did not disappear. In the context of subject classification, TCM is usually classified to TCM historiography for its historic nature, while TCM historiography is somewhat medical because of TCM's medical nature. Considering the particularity of TCM, the tension between history and medicine should be maintained in the TCM historiography research.

[On relativity of the cognition of health].

The people's cognition of health has changed, from less to more. WHO (World Health Organization) put forward the definition of health, and revise it constantly. Although the people's cognition of health is developed continually, the cognition still has its own relativity, because of the difference of cognition methods, the changes of the frame of reference and uncertainty of the standard of judgment.