[Meta-analysis of effect of Qishen Yiqi Dripping Pills combined with Western medicine on adverse cardiovascular events and quality of life after percutaneous coronary intervention].

To systemically evaluate the effect of Qishen Yiqi Dripping Pills combined with Western medicine on adverse cardiovascular events and quality of life after percutaneous coronary intervention(PCI). A total of 7 Chinese and English databases including CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library and Web of Science were searched by computer to collect the randomized controlled trials(RCTs) on Qishen Yiqi Dripping Pills combined with Western medicine in the treatment of patients with coronary heart disease after PCI with the retrieval time from the database establishment to April 1, 2020. Two researchers independently conducted li-terature screening, data extraction and bias risk assessment. Then, Meta-analysis was performed by using RevMan 5.3 software. A total of 31 RCTs were included, involving 3 537 patients. The results of Meta-analysis showed that in terms of major adverse cardiovascular events(MACE) after PCI, the combination of Qishen Yiqi Dripping Pills could significantly reduce the recurrence of angina pectoris, incidence of arrhythmia, heart failure and re-revascularization, and the effect was better than that of Western medicine treatment alone. However, there was no significant difference between the two groups in the improvement of non-fatal myocardial infarction, cardiac death, stent restenosis, stroke and other adverse cardiovascular events. In terms of improving left ventricular ejection fraction(LVEF), 6 min walking test(6 MWT), high-sensitivity C-reactive protein(hs-CRP) and Seattle angina pectoris scale(SAQ), the combination of Qishen Yiqi Dripping Pills and Western medicine treatment had obvious advantages over Western medicine treatment alone in increasing LVEF, 6 MWT and SAQ, and reducing the level of hs-CRP, with statistically significant differences. There were few adverse reactions in both groups, and there was no significant difference between the two groups. The main manifestations were gastrointestinal reactions, rash, gingiva and other small bleeding, and no serious adverse reactions occurred. The above reactions could disappear after drug withdrawal or symptomatic treatment. The application of Qishen Yiqi Dripping Pills combined with Western medicine in the treatment of patients after PCI could reduce the occurrence of MACE, improve the clinical efficacy, quality of life and prognosis in a safe and reliable manner. However, due to the quantity and quality limitations of included studies, more standardized, rigo-rous and high-quality clinical studies are still needed to further verify the above conclusions.

DAPK3 inhibits gastric cancer progression via activation of ULK1-dependent autophagy.

Dysregulation of the balance between cell proliferation and cell death is a central feature of malignances. Death-associated protein kinase 3 (DAPK3) regulates programmed cell death including apoptosis and autophagy. Our previous study showed that DAPK3 downregulation was detected in more than half of gastric cancers (GCs), which was related to tumor invasion, metastasis, and poor prognosis. However, the precise molecular mechanism underlying DAPK3-mediated tumor suppression remains unclear. Here, we showed that the tumor suppressive function of DAPK3 was dependent on autophagy process. Mass spectrometry, in vitro kinase assay, and immunoprecipitation revealed that DAPK3 increased ULK1 activity by direct ULK1 phosphorylation at Ser556. ULK1 phosphorylation by DAPK3 facilitates the ULK1 complex formation, the VPS34 complex activation, and autophagy induction upon starvation. The kinase activity of DAPK3 and ULK1 Ser556 phosphorylation were required for DAPK3-modulated tumor suppression. The coordinate expression of DAPK3 with ULK1 Ser556 phosphorylation was confirmed in clinical GC samples, and this co-expression was correlated with favorable survival outcomes in patients. Collectively, these findings indicate that the tumor-suppressor roles of DAPK3 in GC are associated with autophagy and that DAPK3 is a novel autophagy regulator, which can directly phosphorylate ULK1 and activate ULK1. Thus, DAPK3 might be a promising prognostic autophagy-associated marker.

Chitosan-Stabilized Self-Assembled Fluorescent Gold Nanoclusters for Cell Imaging and Biodistribution in Vivo.

Biocompatible, near-infrared luminescent gold nanoclusters were synthesized in situ using as-prepared chitosan grafted with N-acetyl-l-cysteine (NAC-CS). The fluorescent gold nanoclusters coated with chitosan-N-acetyl-l-cysteine (AuNCs@NAC-CS) were aggregated by multiple ultrasmall gold nanoclusters closing with each other, with strong fluorescence emission at 680 nm upon excitation at 360 nm. AuNCs@NAC-CS did not display any appreciable cytotoxicity on cells even at a concentration of 1.0 mg mL-1. AuNCs@NAC-CS were more insensitive to H2O2 and trypsin compared with fluorescent gold nanoclusters coated with Albumin Bovine V (AuNCs@BSA), which make them have long time imaging in HeLa cells. Furthermore, the obvious fluorescence signal of AuNCs@NAC-CS appeared in the liver and kidney of the normal mice after 6 h injection. And the fluorescence intensity decreased after that because of the highly efficient clearance characteristics of ultrasmall nanoparticles. These findings demonstrated that AuNCs@NAC-CS possessed good fluorescence, low cytotoxicity, and low sensitivity to some content of cells, allowing imaging of the living cells.

Chitosan-coated gold nanorods for cancer therapy combining chemical and photothermal effects.

To develop a novel type of nanoparticle for cancer therapy, gold nanorods (GNRs) are coated with chitosan (CS) derivatives to combine chemical and photothermal effects. Thiol-modified chitosan derivatives chemically conjugated to doxorubicin (DOX) are successfully synthesized and their in vitro effect is evaluated. Functional nanocarriers (DOX-CS-GNR) with good biocompatibility and optical properties are prepared by conjugating chitosan derivatives to GNRs. Two types of structures with different molar ratios of chitosan derivatives and GNRs are successfully obtained. In in vitro studies, GNR-loaded nanoparticles show low cytotoxicity and high potential for anti-cancer effects. Under conditions of short exposure time and low light intensity, DOX-CS-GNR nanocarriers with a side-by-side structure exhibit cytoxicity against tumor cells based on a combination of chemical and photothermal therapeutic effects.

Enhanced uptake and cytotoxity of folate-conjugated mitoxantrone-loaded micelles via receptor up-regulation by dexamethasone.

Folate conjugated amphiphilic polymeric micelles have attracted much attention for active targeted delivery of drugs in folate receptor α (FR-α) positive tumors. However, the efficacy improvement of targeted delivery folate-based nanovehicles was limited by the abundance of FR-α on the surface of tumor cells. Recently, it was found that FR-α expression of Hela cells could be up-regulated by modulators such as dexamethasone, which open a new avenue to enhance the efficiency of targeted delivery from the biological view. In this study, folate-conjugated or plain lipid-core micelles loaded with fluorescent coumarin 6 or mitoxantrone (MTN) were prepared by self-assembly. In addition, FOLR1 mRNA and cell surface FR-α levels were evaluated in Hela cells with dexamethasone treatment. The endocytosis of folate-conjugated or plain micelles loaded with coumarin 6 was examined with confocal microscopy and flow cytometry, which displayed that folate-conjugated micelles can be internalized more efficiently in dexamethasone-treated Hela cells than in normal Hela cells. Moreover, the antitumor activity of folate-conjugated micellar MTN was also improved through up-regulation of FR-α. Therefore, FR-α up-regulation using modulators has great potential to improve the therapeutic efficacy of folate-conjugated nanovehicles in some FR-α positive tumors via receptor-mediated endocytosis.

Spatiotemporal control over growth factor delivery from collagen-based membrane.

Exogenous administration of growth factors has been identified as a potential therapeutic approach for healing wounds. A way to enhance the efficacy of growth factors would be to achieve spatiotemporal control over their delivery to desired sites for an extended period. In this study, we designed and prepared a kind of double-layered collagen membrane, a dense layer and a loose layer, which incorporated basic fibroblast growth factor (bFGF)-loaded chitosan-heparin nanoparticles. The nanoparticles were prepared by polyelectrolyte gelation process and then were sandwiched between the two layers of collagen membrane. The release of model protein human serum albumin (HSA) from the double-layered membrane was tracked by radio-label assay, and the bioactivity of the growth factor on fibroblast cell (L929) was evaluated by MTT assay. The release of protein displayed a spatiotemporal control model and its release in undesired direction was lessened. The bFGF maintained the bioactivities after release from the membranes. Moreover, different release amounts of bFGF from the different layers of the membrane induced significant difference in cell proliferation when the cells were seeded on the different layers of membrane in vitro. This kind of double-layered collagen membrane could have potential applications in the field of tissue repair due to the spatiotemporal control over growth factor delivery, the mild fabrication conditions, and the simple processes.