Effect of glutamine on the systemic innate immune response in broiler chickens challenged with Salmonella pullorum.

BACKGROUND: The objective of this study was to evaluate the effects of glutamine on the growth performance and systemic innate immune response in broiler chickens challenged with Salmonella pullorum. A total of 600 one-day-old Arbor Acres broiler chickens were assigned randomly to 6 dietary treatments with 10 replicates for a 21-day feeding experiment. The experimental treatments were as follows: the control treatment (birds fed the basal diet), the Gln1 treatment, and the Gln 2 treatment (birds fed the basal diet supplemented with 0.5%, and 1.0% Glutamine, respectively). At 3 d of age, half of the birds from each treatment were challenged oral gavage with 2.0 × 104 CFU/mL of S. pullorum suspension (1.0 mL per bird) or an equivalent amount of sterile saline alone, which served as a control. RESULTS: The results showed that S. pullorum infection had adverse effects on the average daily feed intake, average daily gain, and feed conversion ratio of broiler chickens compared with those of the CON treatment on d 7, decreased the spleen and bursa of fabricius relative weights (except on d 21), serum immunoglobulin A (IgA),immunoglobulin G (IgG), and immunoglobulin M (IgM) concentrations, and spleen melanoma differentiation-associated gene 5 (MDA5) and laboratory of genetics and physiology gene 2 (LGP2) mRNA expression levels, and increased the mRNA expression levels of spleen Nodinitib-1 (NOD1), Toll-like receptors 2,4 (TLR2, TLR4), DNA-dependent activator of IFN-regulatory factors (DAI), mitochondrial antiviral-signaling protein (MAVS), P50, P65, and RelB on d 4, 7, 14, and 21. Supplementation with Gln improved the relative weights of the spleen and bursa of Fabricius (except on d 21), increased the serum IgA, IgG, and IgM concentrations and the mRNA expression levels of spleen MDA5 and LGP2, and decreased the mRNA expression levels of spleen NOD1, TLR2, TLR4, DAI, MAVS, P50, P65, and RelB of S. pullorum-challenged broiler chickens. CONCLUSION: These results indicate that Gln might stimulate the systemic innate immune responses of the spleen in broiler chickens challenged with S. pullorum.

Meta-analysis of the effectiveness and safety of Xingnaojing and naloxone in the treatment of carbon monoxide poisoning.

BACKGROUND: To evaluate the effectiveness and safety of Xingnaojing combined with naloxone in the treatment of carbon monoxide poisoning. METHODS: By retrieving the literatures published in the databases of PubMed, Cochrane Library, Web of Science, Embase, Wanfang Database, Weipu Database, and China National Knowledge Infrastructure from January 2010 to September 2021, the data of randomized controlled trials (RCTs) of Xingnaojing combined with naloxone in the treatment of carbon monoxide poisoning were extracted. The methodological quality of the included RCTs was evaluated by using the tools of bias risk evaluation of Cochrane Collaboration, and the data were statistically analyzed by using RevMan 5.3 software. RESULTS: A total of 20 literatures were included, involving in 771 cases treated by Xingnaojing combined with naloxone and 761 cases in the control group. The effective rate of the experimental group is higher than that of the control group [risk ratio (RR) = 1.20, 95% confidence interval (CI) (1.14, 1.26)]. The average awake time (STD mean difference = -2.08, 95% CI [-2.60, -1.56]), physical recovery time (STD mean difference = -2.94, 95% CI [-3.59, -2.28]), delayed encephalopathy (RR = 0.44, 95% CI [0.31, 0.62]), and adverse reactions (RR = 0.23, 95% CI [0.10, 0.54]) was lower than that of the control group. CONCLUSION: Xingnaojing combined with naloxone in the treatment of carbon monoxide poisoning is significantly superior to naloxone, but it still needs to be further verified by high-quality large samples of RCTs.

Nonsteroidal anti-inflammatory drug diclofenac accelerates the emergence of antibiotic resistance via mutagenesis.

Overuse of antimicrobial agents are generally considered to be a key factor in the occurrence of antibiotic resistance bacteria (ARB). Nevertheless, it is unclear whether ARB can be induced by non-antibiotic chemicals such as nonsteroidal anti-inflammatory drug (NSAID). Thus, the objective of this study is to investigate whether NSAID diclofenac (DCF) promote the emergence of antibiotic resistance in Escherichia coli K12 MG1655. Our results suggested that DCF induced the occurrence of ARB which showed hereditary stability of resistance. Meanwhile, gene variation was identified on chromosome of the ARB, and DCF can cause bacterial oxidative stress and SOS response. Subsequently, transcriptional levels of antioxidant (soxS, sodA, sodC, gor, katG, ahpF) and SOS (recA, lexA, uvrA, uvrB, ruvA, ruvB, dinB, umuC, polB) system-related genes were enhanced. However, the expression of related genes cannot be increased in high-dosage treatment compared with low-dosage samples because of cytotoxicity and cellular damage. Simultaneously, high-dosage DCF decreased the mutation frequency but enhanced the resistance of mutants. Our findings expand our knowledge of the promoting effect on the emergence of ARB caused by DCF. More attention and regulations should be given to these potential ecological and health risks for widespread DCF.

Prognostic Impact of Aberrantly Expressed Protein-coding Gene Associated With Gastric Cancer's Regulatory T Cells, Based on Online Databases.

Context: Gastric cancer (GC) remains one of the most prevalent malignancies worldwide, and no effective cure exists for advanced GC. Clinicians believe that molecularly targeted therapy through PCGs may replace surgery, radiotherapy, and other treatments as a breakthrough in curing malignancies. Objective: The study intended to examine the impact of aberrant expression of the protein-coding genes (PCGs) associated with regulatory T cells on the prognosis of patients with gastric cancer (GC). Design: The research team performed a genetic study through research of genetic data in online databases. Setting: The study took place at Zhongda Hospital. Outcome Measures: The research team selected a publicly available dataset, genetic suppressor element 109476 (GSE109476), from the Gene Expression Omnibus (GEO) database for differential gene analysis, gene ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to screen for PCGs associated with regulatory T cells as well as the Gene Expression Profiling Interactive Analysis (GEPIA) database with the Kaplan-Meier Plotter database to analyze the expression of the above PCGs in GC and the prognostic impact on GC. Results: The GEO2R analysis found 315 differentially expressed PCGs in GSE109476, among which nine PCGs were associated with regulatory T cells: (1) chemokine (C-C motif) ligand 19 (CCL19), (2) CCL21, (3) C-C chemokine receptor type 7 (CCR7), (4) cluster of differentiation 70 (CD70), (5) ephrin B3 (EFNB3), (6) early growth response 3 (EGR3), (7) interleukin-7 receptor (IL7R), (8) galectin-1 (LGALS1), and (9) tumor necrosis factor (TNF) receptor superfamily member 13C (TNFRSF13C). The GEPIA database indicated that no significant differences existed between the expression of CCL19, CCL21, CD70, EFNB3, EGR3, IL7R, and TNFRSF13C in stomach adenocarcinoma (STAD) tissues and that in normal tissues (P > .05), while expressions of CCR7 and LGALS1 were significantly elevated in STAD tissues compared to the normal tissues (P < .05). The Kaplan-Meier Plotter database analysis, on the other hand, showed a significant relationship between all of the above-mentioned PCGs, except CCL19, and the prognosis of GC. Conclusions: CCL19, CCL21, CCR7, CD70, EFNB3, EGR3, IL7R, LGALS1, and TNFRSF13C are PCGs are differentially expressed in GC and closely associated with regulatory T cells. They may affect the occurrence and development of GC through a variety of pathways, including regulation of immune infiltration and inflammation, and are of great potential research value.

Meta-analysis of the effectiveness and safety of Shenyankangfu tablets combined with losartan potassium in the treatment of chronic glomerulonephritis.

OBJECTIVE: To conduct a systematic review of the efficacy and safety of Shenyankangfu tablets in combination with losartan potassium in the treatment of chronic glomerulonephritis. METHOD: We searched PubMed, Embase, Cochrane Library, CNKI, WanFang Data, and WeiPu for comparative studies on Shenyankangfu tablets in combination with losartan potassium in the treatment of chronic glomerulonephritis. The search period runs from the establishment of the database until September 2021. Data extraction and quality evaluation were carried out on the documents that met the inclusion criteria, and a meta-analysis of the included literature was conducted using the RevMan5.3 software. RESULTS: A total of 17 randomized controlled trials that met the inclusion criteria were included, with a total sample size of 1680 patients (841 patients in the study group and 839 in the control group). The effective rate was significantly higher in the study group than in the control group [RR = 1.22, 95% CI (1.16, 1.27), P < 0.00001]. In addition, 24-hour urine protein levels [SMD = -1.11, 95% CI (-1.40, -0.83), P < 0.00001], urine NAG enzyme [SMD = -0.99, 95% CI (-1.27, -0.72), P < 0.00001], leukotactin-1 [SMD = -2.43, 95% CI (-3.50, -1.35), P < 0.00001], and the incidence of adverse reactions [RR = 0.43, 95% CI (0.28, 0.66), P < 0.00001] were lower in the study group when compared to the control group. CONCLUSION: It is safer to treat chronic glomerulonephritis with Shyenyankangfu tablets in combination with losartan potassium. At the same time, it alleviates disease-related symptoms, reduces the influence of cytokine levels, and has fewer adverse reactions, making it more conducive to disease recovery. However, additional multi-center, randomized, control trials with large sample sizes must be conducted to confirm the findings.

BuFeiXiaoJiYin ameliorates the NLRP3 inflammation response and gut microbiota in mice with lung cancer companied with Qi-yin deficiency.

INTRODUCTION: NLRP3 inflammasome responses and gut microbiota have been shown an important role in lung cancer, however, the relationship between gut microbiota and NLRP3 inflammasome responses in lung cancer with Qi-yin deficiency remains elusive. METHODS: To investigate the effect of the traditional Chinese medicine BuFeiXiaoJiYin (BFXJY) on NLRP3 inflammasome responses and dysbiosis in lung cancer with Qi-yin deficiency, the female BALB/cA-nu mice were treated with LPS and ATP to induce inflammation, and were intragastrically treated with warm Chinese medicine and smoked with shavings to induce Qi-yin deficiency, as well as were injected with 1 × 107/ml A549 cells to simulate lung cancer. Then the three different doses of BuFeiXiaoJiYin (BFXJY) and positive control (CRID3) were used for intervention in mice for 27 consecutive days. Then, we estimated the protection effect of BFXJY on lung cancer mice with Qi-yin deficiency, through deterring tumor growth, NLRP3 inflammasome, PKC signaling, and homeostasis of gut microbiota. RESULTS: In this study, we found that BFXJY could inhibit the tumor growth in lung cancer with Qi-yin deficiency by reducing the production of IL-1ß and IL-18 and inhibiting NLRP3 inflammasome activation, which might be associated with the inhibition of PKC signaling. Furthermore, BFXJY could promote microbial diversity and balance the microbial composition changes induced by inflammation and Qi-yin deficiency in lung cancer. CONCLUSION: BuFeiXiaoJiYin ameliorates the NLRP3 inflammation response and gut microbiota in mice with lung cancer companied with Qi-yin deficiency. Our study provides a theoretical basis for the clinical development of therapeutic drugs targeting to treat lung cancer.

A Microcosmic Syndrome Differentiation Model for Metabolic Syndrome with Multilabel Learning.

BACKGROUND: Metabolic syndrome (MS) is a complex multisystem disease. Traditional Chinese medicine (TCM) is effective in preventing and treating MS. Syndrome differentiation is the basis of TCM treatment, which is composed of location and/or nature syndrome elements. At present, there are still some problems for objective and comprehensive syndrome differentiation in MS. This study mainly proposes a solution to two problems. Firstly, TCM syndromes are concurrent, that is, multiple TCM syndromes may develop in the same patient. Secondly, there is a lack of holistic exploration of the relationship between microscopic indexes, and TCM syndromes. In regard to these two problems, multilabel learning (MLL) method in machine learning can be used to solve them, and a microcosmic syndrome differentiation model can also be built innovatively, which can provide a foundation for the establishment of the next model of multidimensional syndrome differentiation in MS. METHODS: The standardization scale of TCM four diagnostic information for MS was designed, which was used to obtain the results of TCM diagnosis. The model of microcosmic syndrome differentiation was constructed based on 39 physicochemical indexes by MLL techniques, called ML-kNN. Firstly, the multilabel learning method was compared with three commonly used single learning algorithms. Then, the results from ML-kNN were compared between physicochemical indexes and TCM information. Finally, the influence of the parameter k on the diagnostic model was investigated and the best k value was chosen for TCM diagnosis. RESULTS: A total of 698 cases were collected for the modeling of the microcosmic diagnosis of MS. The comprehensive performance of the ML-kNN model worked obviously better than the others, where the average precision of diagnosis was 71.4%. The results from ML-kNN based on physicochemical indexes were similar to the results based on TCM information. On the other hand, the k value had less influence on the prediction results from ML-kNN. CONCLUSIONS: In the present study, the microcosmic syndrome differentiation model of MS with MLL techniques was good at predicting syndrome elements and could be used to solve the diagnosis problems of multiple labels. Besides, it was suggested that there was a complex correlation between TCM syndrome elements and physicochemical indexes, which worth future investigation to promote the development of objective differentiation of MS.

[Research progress on chemical constituents and bioactivities of Lepidium meyenii].

Maca( Lepidium meyenii) known as the " national treasure of Peru" and " South American ginseng",is annual or biennial herbs of the genus Lepidium in Cruciferae. It mainly contains proteins,amino acids,polysaccharides,alkaloids( including:macamides,imidazoles,hydroxypyridines,carbazoles,organic amines and so on),glucosinolates,macaenes,thioethylurea,sterols and other chemical constituents. In recent years,more and more studies have found that it could treat osteoporosis and improve prostatehyperplasia,and possessed anti-cancer,female climacteric syndrome,rheumatism,antioxidant and other pharmacological effects. In this paper,the chemical constituents and bioactivity of Maca were reviewed,which could provide the basis for the further development and utilization of Maca.

N-acetylcysteine alleviated bisphenol A-induced testicular DNA hypermethylation of rare minnow (Gobiocypris rarus) by increasing cysteine contents.

Ubiquitous BPA exposure resulted in DNA methylation errors and oxidative stress. Numerous studies have demonstrated that oxidative stress can lead to changes in DNA methylation levels and supplementation with antioxidants, including N-acetylcysteine (NAC), was able to restore these changes. Our previous study supposed that BPA-induced de novo synthesis of glutathione (GSH) promoted DNA methylation process in Gobiocypris rarus testes. To validate this conjecture and explore the protective effects of NAC on BPA toxicity, the present study was carried out. Adult male G. rarus was treated with 225 µg L-1 BPA and/or NAC for 7 days. The sperm motility and DNA integrity of G. rarus were determined. Meanwhile, the levels of 5-methylcytosine (5mC), GSH, hydrogen peroxide (H2O2), DNA methyltransferase proteins (DNMTs), γ-glutamyl cysteine synthetase (GCS), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), homocysteine (HCY), nicotinamide adenine dinucleotide phosphate (NADPH) and cysteine in the testes were detected. Furthermore, the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were measured. Results indicated that NAC addition resulted in increase of cysteine contents and partially inhibited the BPA-induced DNA hypermethylation of G. rarus testes. In addition, the changes in DNA methylation levels in the testes after BPA and/or NAC treatment might be controlled by DNA methylation process that mediated by DNMTs. Moreover, BPA exposure caused oxidative stress in the testes and the elimination of H2O2 might be mainly accomplished by CAT while it changed to mainly through GPx after NAC supplement. Finally, the positive response of testicular antioxidant enzyme system and the antioxidant activity of NAC itself protected sperm motility and DNA integrity from oxidative damage in each group.

Therapeutic effect of acupuncture combined electrical stimulation on aged patients with post‐stroke de‐pression／ / 心血管康复医学杂志

To explore therapeutic effect of acupuncture combined electrical stimulation on aged patients with post‐stroke depression .Methods : A total of 78 patients with post‐stroke depression were randomly and equally divided into routine treatment group (received health education based on routine treatment ) and combined treatment group (received acupuncture combined low‐frequency electrical stimulation based on routine treatment group ).After four‐week treatment , score of Hamilton rating scale for depression (HAMD) and therapeutic effect were compared between two groups .Results : Compared with before treatment , there was significant reduction in HAMD score in two groups after treatment ;compared with routine treatment group after treatment , there was significant reduction in HAMD score [(19.72 ± 2. 04) scores vs.(14. 94 ± 1. 86) scores] in combined treatment group , P＝0. 001 all.To‐tal effective rate of combined treatment group was significantly higher than that of routine treatment group (87.18% vs.64.1%, P＝0.018).Conclusion : Acupuncture combined low‐frequency electrical stimulation possesses significant therapeutic effect on post‐stroke depression , which is worthy of clinical application .

Three new cassane diterpenes from the seeds of Caesalpinia minax Hance.

Four fractions were prepared from the crude extract of Caesalpinia minax Hance and the inhibitory activity of nitric oxide (NO) production release of RAW 264.7 cells stimulated by lipopolysaccharide (LPS) was evaluated. The ethyl acetate (EtOAc) fraction showed obvious inhibitory effect. Bioassay-guided fractionation led to the isolation of three new cassane diterpenes, caesalmin X (1), caesalmin Y (2) and caesalmin Z (3), together with 19 known cassane diterpenoids (4-22). Their structures were mainly characterised on the basis of extensive spectroscopic analyses and comparison with reported data. Moreover, three compounds (20-22) which possessed furanditerpenoid 7,17-lactone structures, displayed moderate activities, with IC50 value of 29.85, 27.38 and 25.40 µM, respectively.

Solanerioside A, an unusual 14,15-dinor-cyclophytane glucoside from the leaves of Solanum erianthum.

Solanerioside A (1), the first example of a diterpenoid glucoside featuring a 14,15-dinor-cyclophytane scaffold, together with three known terpene glucosides (2-4) were isolated from the methanol extract of the leaves of Solanum erianthum (Solanaceae). The structure of 1 was mainly characterised on the basis of extensive spectroscopic analyses, especially from the 2D NMR spectra. In addition, the spectroscopic data of (6E, 10E)-5,12-dihydroxy-ß-nerolidol 5-O-ß-D-glucopyranoside (3) were reported for the first time. However, these compounds did not display obvious inhibition of LPS-induced NO release in RAW264.7 cells and anti-tumour activity against A549, HepG2, Hela and MCF-7 cells in vitro.

Effect of Catnip Charcoal on the In Vivo Pharmacokinetics of the Main Alkaloids of Rhizoma Coptidis.

This study aims to explore the effect of catnip Nepeta cataria (CNC) charcoal on the pharmacokinetics of the main alkaloids of Rhizoma Coptidis in vivo. Twenty-four rabbits were randomly divided into four groups and given oral administration of an aqueous extract of Rhizoma Coptidis (RCAE), RCAE plus CNC, RCAE plus activated carbon (AC), or distilled water, respectively. Plasma samples were collected after administration. The concentrations of berberine, coptisine, palmatine, and epiberberine in plasma were measured by high-performance liquid chromatography (HPLC). The pharmacokinetics data were calculated using pharmacokinetic DAS 2.0 software. The results showed that the area under the concentration-time curve (AUC) of berberine increased, while the AUC of coptisine, palmatine, and epiberberine decreased in the rabbits that received RCAE plus CNC. Meanwhile, the AUC of berberine, coptisine, palmatine, and epiberberine decreased in the group given RCAE plus AC. The difference of main pharmacokinetics parameters among the four groups was significant (P < 0.05). This study showed that CNC improved the bioavailability of berberine in comparison to AC and prolonged its release in comparison to RCAE alone. However, it decreased the bioavailability of coptisine, palmatine, and epiberberine. In comparison, AC uniformly declined the bioavailability of berberine, coptisine, palmatine, and epiberberine.

Evidence that ghrelin may be associated with the food intake of gibel carp (Carassius auratus gibelio).

Ghrelin, a non-amidated peptide hormone, is a potent anorectic neuropeptide implicated in feeding regulation in mammals and non-mammalian vertebrates. However, the involvement of ghrelin in the feeding behavior of teleosts has not been well understood. To better understand the role of ghrelin in the regulation of appetite in fish, in this study, we cloned the cDNAs encoding ghrelin and investigated their mRNA distributions in gibel carp tissues. We also assessed the effects of different nutritional status on ghrelin mRNA abundance. Ghrelin mRNAs were ubiquitously expressed in ten tissues (intestine, liver, brain, mesonephron, head kidney, spleen, skin, heart, muscle, gill and pituitary gland), and relatively high expression levels were detected in the gut. Postprandial studies analysis revealed a significant postprandial decrease in ghrelin mRNA expression in the gut (1 and 3 h after the regular feeding time). In addition, ghrelin mRNA expression in the gut significantly increased at day 7 after fasting and declined sharply after refeeding, which suggested that ghrelin might be involved in the regulation of appetite in gibel carp. Overall, our result provides basis for further investigation into the regulation of feeding in gibel carp.

Enantiomeric Neolignans and a Sesquiterpene from Solanum erianthum and Their Absolute Configuration Assignment.

One pair of new C-8-C-3'/C-7-O-C-4' linked neolignan enantiomers (1a/1b) and one new guaiane sesquiterpene (2) first featuring the 1(2),9(10)-conjugated double bond were isolated from the stems of Solanum erianthum (Solanceae). Their structures were characterized on the basis of extensive spectroscopic analyses, especially from their 2D nuclear magnetic resonance (NMR) spectra. The absolute configurations of 1a/2b were rigorously elucidated by electronic circular dichroism (ECD) experiments combined with the reversed helicity rule for the 2,3-dihydrobenzo[b]furan chromophore, and compound 2 is the first report on the sterochemical assignment of a guaiane sesquiterpene by using the allylic axial chirality rule for the conjugated diene chromophore in combination with the calculated ECD spectrum.

Two new glycosides isolated from Sapindus mukorossi fruits: effects on cell apoptosis and caspase-3 activation in human lung carcinoma cells.

Two new glycosides (1, 2) and two saponins (3, 4) were isolated from the fruits of Sapindus mukorossi Gaertn. The two glycosides were designated as sapindoside G (1) and 4'',4'''''-O-diacetylmukurozioside IIa (2). All four compounds exhibited inhibitory effects against A549 human lung adenocarcinoma cells with inhibition rates up to 69.2-83.3% at a concentration of 100 µg/mL. Flow cytometric analysis revealed that compounds 1-4 could suppress A549 cell growth by promoting cell apoptosis, which was related to the activation of caspase-3.

Diterpenoids from aerial parts of Flickingeria fimbriata and their nuclear factor-kappaB inhibitory activities.

Chemical investigation of the aerial parts of Flickingeria fimbriata (Bl.) Hawkes resulted in isolation of sixteen ent-pimarane diterpenoids, including five rare 16-nor-ent-pimarane diterpenoids, two 15,16-dinor-ent-pimarane diterpenoids and one ent-pimarane diterpenoid. Structures were mainly elucidated by extensive spectroscopic analysis, and their absolute configurations were unequivocally determined by the exciton chirality method, the modified Mosher's method, the CD experiments (including Snatzke's method) and chemical transformations, respectively. All the isolated compounds were screened for inhibitory effects on the nuclear factor-kappaB (NF-κB) in lipopolysaccharide (LPS) induced murine macrophage RAW264.7 cells, using a NF-κB-dependent luciferase reporter gene assay. Several of these compounds displayed comparable or even better activities than the positive control pyrrolidinedithiocarbamate (PDTC) (IC50=26.3 µM) with IC50 values in the range of 14.7-29.2 µM and structure-activity relationships are briefly proposed.

A new triterpenoid saponin and an oligosaccharide isolated from the fruits of Sapindus mukorossi.

A new triterpenoid saponin (1) and a new oligosaccharide (2), together with three known saponins (3-5), have been isolated from n-BuOH extract of the fruits of Sapindus mukorossi Gaertn. The structures were elucidated using detailed analysis of one- and two-dimensional nuclear magnetic resonance spectra along with their mass spectrometric data and the results of acid hydrolysis. Of the isolated compounds 1 and 3-5 displayed cytotoxic effects against human cancer cell lines in A-549 (lung carcinoma), MDA-231 (breast carcinoma) and PC-3 (prostatic carcinoma).

"Re-evaluation upon suspected event" is an approach for post-marketing clinical study: lessons from adverse drug events related to Bupleuri Radix preparations / 中国中药杂志

We revisited the "Xiao Chaihu Decoction event (XCHDE)" occurred in late 1980s in Japan and the Bupleuri Radix related adverse drug reaction (ADR) reports in China After careful review, comparison, analysis and evaluation, we think the interstitial pneumonitis, drug induced Liver injury (DILI) and other severe adverse drug envents (ADEs) including death happened in Japan is probably results from multiple factors, including combinatory use of XCHDE with interferon, Kampo usage under modern medicine theory guidance, and use of XCHD on the basis of disease diagnosis instead of traditional Chinese syndrome complex differentiation. There are less ADE case reports related to XCHD preparation in China compared to Japan, mostly manifest with hypersensitivity responses of skin and perfuse perspiration. The symptoms of Radix Bupleuri injection related ADEs mainly manifest hypersensitivity-like response, 2 cases of intravenous infusion instead of intramuscular injection developed hypokalemia and renal failure. One case died from severe hypersensitivity shock. In Chinese literatures, there is no report of the interstitial pneumonitis and DILI associated with XCHDG in Japan. So far, there is no voluntary monitoring data and large sample clinical research data available. The author elaborated the classification of "reevaluation" and clarified "re-evaluation upon events" included the reaction to the suspected safety and efficacy events. Based on the current status of the clinical research on the Radix Bupleuri preparations, the author points out that post-marketing "re-evaluation upon suspected event" is not only a necessity of continuous evaluation of the safety, efficacy of drugs, it is also a necessity for providing objective clinical research data to share with the international and domestic drug administrations in the risk-benefit evaluation. It is also the unavoidable pathway to culture and push the excellent species and famous brands of TCM to the international market, in that it enhances the pharmaceutical manufactures the ability to control enterprise risk and eliminate the negative impact on traditional Chinese medicine. With the widely used and ADR report concentrated Radix Bupleuri injection as an example, the author provide a new approach to post-marketing clinical research.

Novel sorbicillin analogues from the marine fungus Trichoderma sp. associated with the seastar Acanthaster planci.

Two novel sorbicillinoid analogues, (4'Z)-sorbicillin (1) and (2S)-2,3-dihydro-7-hydroxy-6-methyl-2-[(E)-prop-1-enyl]-chroman-4-one (2), together with three known compounds, (2S)-2,3-dihydro-7-hydroxy-6,8-dimethyl-2-[(E)-prop-1-enyl]-chroman-4-one (3), sorbicillin (4), and 2',3'-dihydrosorbicillin (5), were isolated from the culture broth of the fungus Trichoderma sp. associated with the seastar Acanthaster planci. Their structures were determined by analysis of the NMR and MS data. Compound I was the first example with a Z-configuration of the C-4'/C-5' double bond in the sorbyl side chain. Compounds 2 and 3 were uncommon monomeric sorbicillinoids with a cyclic sorbyl chain. 2, 3 and 5 showed moderate cytotoxic activities against various cancer cell lines.