[Expert consensus on clinical application of GBE50 Dispersible Tablets for ischemic cardiovascular and cerebrovascular diseases].

Ginkgo biloba Extract( GBE50) Dispersible Tablets is a new standardized prescription,which is widely used in the treatment of ischemic cardiovascular and cerebrovascular diseases. However,there are still many problems in its clinical application.Rational and safe use of GBE50 Dispersible Tablets is pivotal to the medication safety and clinical prognosis of patients. This consensus has been jointly formulated by clinical experts of traditional Chinese medicine and western medicine in cardiovascular and cerebrovascular diseases and followed the Manual for the Clinical Experts Consensus of Chinese Patent Medicine published by the China Association of Chinese Medicine. The present study identified clinical problems based on clinical investigation,searched the research papers according to PICO clinical problems,carried out evidence evaluation,classification,and recommendation by GRADE system,and reached the expert consensus with nominal group technique. The consensus combines evidence with expert experience. Sufficient evidence of clinical problems corresponds to " recommendations",while insufficient evidence to " suggestions". Safety issues of GBE50 Dispersible Tablets,such as indications,usage and dosage,and medication for special populations,are defined to improve clinical efficacy,promote rational medication,and reduce drug risks. This consensus needs to be revised based on emerging clinical issues and evidencebased updates in practical applications in the future.

Study on the Multitarget Mechanism and Active Compounds of Essential Oil from Artemisia argyi Treating Pressure Injuries Based on Network Pharmacology.

In order to comprehensively explore multitarget mechanism and key active compounds of Artemisia argyi essential oil (AAEO) in the treatment of pressure injuries (PIs), we analyzed the biological functions and pathways involved in the intersection targets of AAEO and PIs based on network pharmacology, and the affinity of AAEO active compounds and core targets was verified by molecular docking finally. In our study, we first screened 54 effective components according to the relative content and biological activity. In total, 103 targets related to active compounds of AAEO and 2760 targets associated with PIs were obtained, respectively, and 50 key targets were overlapped by Venny 2.1.0. The construction of key targets-compounds network was achieved by the STRING database and Cytoscape 3.7.2 software. GO analysis from Matespace shows that GO results are mainly enriched in biological processes, including adrenergic receptor activity, neurotransmitter clearance, and neurotransmitter metabolic process. KEGG analysis by the David and Kobas website shows that the key targets can achieve the treatment on PIs through a pathway in cancer, PI3K-Akt signaling pathway, human immunodeficiency virus 1 infection, MAPK signaling pathway, Wnt signaling pathway, etc. In addition, molecular docking results from the CB-Dock server indicated that active compounds of AAEO had good activity docking with the first 10 key targets. In conclusion, the potential targets and regulatory molecular mechanisms of AAEO in the treatment of PIs were analyzed by network pharmacology and molecular docking. AAEO can cure PIs through the synergistic effect of multicomponent, multitarget, and multipathway, providing a theoretical basis and new direction for further study.

Gandouling Tablets Inhibit Excessive Mitophagy in Toxic Milk (TX) Model Mouse of Wilson Disease via Pink1/Parkin Pathway.

OBJECTIVE: Gandouling (GDL) tablet is a Chinese patent medicine approved by the National Medical Product Administration, which is used to treat Wilson disease (WD) in China. In this study, we aimed to investigate the effects of GDL on mitophagy in the hippocampus in the toxic milk (TX) mouse model of WD. METHODS: Mice were randomly divided into the following four groups: control, Wilson (model group), D-penicillamine (DPA), and GDL groups. The animal behaviors were evaluated by the water maze experiment, traction test, and pole test. Transmission electron microscopy was used for the detection of mitochondrion structure. An enzyme-linked immunosorbent assay (ELISA) was performed for the analysis of the changes in liver function. Colocalization of mitophagy-related proteins was detected by fluorescence microscopy. Western blotting (WB) and reverse transcription-polymerase chain reaction (RT-PCR) were conducted for the detection of protein expression and mRNA levels, respectively. RESULTS: Significant reduction in neurological impairments was observed in the WD model group. All of these results were significantly reversed by GDL intervention. Compared with the levels in the Wilson group, the levels of alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), and albumin (ALB) changed obviously. Colocalization between mitophagy-related proteins pink1, parkin, and mitochondria was changed significantly. The mitophagy-related mRNA (pink1, parkin, and LC3II) and protein expression levels (pink1, parkin, and the rate of LC3II/LC3I) were decreased significantly, while p62 was remarkably increased after GDL intervention. CONCLUSION: Our findings indicated that the neuroprotective mechanism of GDL may occur via the inhibition of excessive mitophagy through the regulation of the pink1/parkin pathway in the TX mouse brain of WD.

Evidence for reductions in floral attractants with increased selfing rates in two heterandrous species.

Although theoretical models predict low allocation to attractive structures with increased selfing in animal-pollinated plants, empirical measurement of the reproductive costs and benefits is complicated. Here, floral sex allocation was compared in two nectarless heterandrous species with different mating systems: Monochoria korsakowii (Pontederiaceae), which has moderate outcrossing rates, and Monochoria vaginalis, a predominant selfer. In both species, mirror-image flowers have one large dark-purple anther and five small yellow anthers. Experimental evidence is provided for functional differences between the two sets of anthers using data on pollinator visitation, pollen removal and deposition, and seed set after hand pollinations. Flower manipulations in bee-pollinated M. korsakowii demonstrated different functions of the two sets of anthers: the yellow (feeding) anthers function to attract pollinators, but have similar pollen performance to the purple (pollinating) anthers. Furthermore, a disproportional reduction in pollen production of the feeding anthers in the selfing species was found. This differential allocation between feeding and pollinating anthers in heterandrous species has not been recognized before. The finding of reduced allocation to attractive structures with an increase in the rate of self-fertilization supports the theory of sex allocation.

Pollinator response to female and male floral display in a monoecious species and its implications for the evolution of floral dimorphism.

Pollinator-mediated selection has been hypothesized as one cause of size dimorphism between female and male flowers. Flower number, ignored in studies of floral dimorphism, may interact with flower size to affect pollinator selectivity. In the present study, we explored pollinator response, and estimated pollen receipt and removal, in experimental populations of monoecious Sagittaria trifolia, in which plants were manipulated to display three, six, nine or 12 female or male flowers per plant. In this species, female flowers are smaller but have a more compressed flowering period than males, creating larger female floral displays. Overall, pollinators preferred to visit male rather than female displays of the same size. Both first visit per foraging bout and visitation rates to female displays increased with display size. However, large male displays did not show increased attractiveness to pollinators. A predicted relationship that pollen removal, rather than pollen receipt, is limited by pollinator visitation was confirmed in the experimental populations. The results suggest that the lack of selection on large male displays may affect the evolution of floral dimorphism in this species.

Temporal floral sex allocation in protogynous Aquilegia yabeana contrasts with protandrous species: support for the mating environment hypothesis.

We tested one of the predictions of Brunet and Charlesworth (1995) that relative floral sex allocation will vary temporally with the mating environment and that the form of dichogamy (protandry vs. protogyny) will select for the pattern of variation in male versus female resource allocation. In many hermaphroditic plant species, allocation to female function (ovule number) decreases from early to late flowers within inflorescences as a result of resource limitation or ontogenetic changes. This pattern may obscure the effects of the mating environment and dichogamy on selection for allocation patterns in protandrous species (male allocation increases regardless). By examining a protogynous species the alternative pattern of temporal variation in resource allocation is predicted, namely that allocation to male function should decrease (or female allocation increase) throughout the flowering sequence. This pattern was observed in protogynous Aquilegia yabeana (Ranunculaceae), in which ovule number per flower remained constant whereas pollen number decreased in sequentially blooming flowers. These observations support the temporal sex allocation hypothesis of Brunet and Charlesworth (1995).