OBJECTIVE: To explore the effect of cytokine levels on early death and coagulation function of patients with newly diagnosed acute promyelocytic leukemia (APL). METHODS: Routine examination was performed on 69 newly diagnosed APL patients at admission. Meanwhile, 4 ml fasting venous blood was extracted from the patients. And then the supernatant was taken after centrifugation. The concentrations of cytokines, lactate dehydrogenase (LDH) and ferritin were detected by using the corresponding kits. RESULTS: It was confirmed that cerebral hemorrhage was a major cause of early death in APL patients. Elevated LDH, decreased platelets (PLT) count and prolonged prothrombin time (PT) were high risk factors for early death (P <0.05). The increases of IL-5, IL-6, IL-10, IL-12p70 and IL-17A were closely related to the early death of newly diagnosed APL patients, and the increases of IL-5 and IL-17A also induced coagulation disorder in APL patients by prolonging PT (P <0.05). In newly diagnosed APL patients, ferritin and LDH showed a positive effect on the expression of IL-5, IL-10 and IL-17A, especially ferritin had a highly positive correlation with IL-5 (r =0.867) and IL-17A (r =0.841). Moreover, there was a certain correlation between these five high-risk cytokines, among which IL-5 and IL-17A (r =0.827), IL-6 and IL-10 (r =0.823) were highly positively correlated. CONCLUSION Elevated cytokine levels in newly diagnosed APL patients increase the risk of early bleeding and death. In addition to the interaction between cytokines themselves, ferritin and LDH positively affect the expression of cytokines, thus affecting the prognosis of APL patients.
Humans ; Leukemia, Promyelocytic, Acute/diagnosis* ; Cytokines/metabolism* ; Interleukin-10 ; Interleukin-17/metabolism* ; Interleukin-6/metabolism* ; Interleukin-5/metabolism* ; Blood Coagulation Disorders ; Ferritins ; Tretinoin

Novel drug discovery from the active ingredients of traditional Chinese medicine is the most distinctive feature and advantageous field of China, which has provided an unprecedented opportunity. However, there are still problems such as unclear functional substance basis, action targets and mechanism, which greatly hinder the clinical transformation of active ingredients in traditional Chinese medicine. Based on the analysis of the current status and progress of innovative drug research and development in China, this paper aimed to explore the prospect and difficulties of the development of natural active ingredients from traditional Chinese medicine, and to explore the efficient discovery of trace active ingredients in traditional Chinese medicine, and obtain drug candidates with novel chemical structure, unique target/mechanism and independent intellectual property rights, in order to provide a new strategy and a new model for the development of natural medicine with Chinese characteristics.
Medicine, Chinese Traditional ; Drugs, Chinese Herbal/chemistry* ; Research ; Drug Discovery ; China

Unlike healthy, non-transformed cells, the proteostasis network of cancer cells is taxed to produce proteins involved in tumor development. Cancer cells have a higher dependency on molecular chaperones to maintain proteostasis. The chaperonin T-complex protein ring complex (TRiC) contains eight paralogous subunits (CCT1-8), and assists the folding of as many as 10% of cytosolic proteome. TRiC is essential for the progression of some cancers, but the roles of TRiC subunits in osteosarcoma remain to be explored. Here, we show that CCT4/TRiC is significantly correlated in human osteosarcoma, and plays a critical role in osteosarcoma cell survival. We identify a compound anticarin-β that can specifically bind to and inhibit CCT4. Anticarin-β shows higher selectivity in cancer cells than in normal cells. Mechanistically, anticarin-β potently impedes CCT4-mediated STAT3 maturation. Anticarin-β displays remarkable antitumor efficacy in orthotopic and patient-derived xenograft models of osteosarcoma. Collectively, our data uncover a key role of CCT4 in osteosarcoma, and propose a promising treatment strategy for osteosarcoma by disrupting CCT4 and proteostasis.

With increasing morbidity and mortality, acute myocardial infarction (AMI) has become one of the major causes of human death, leading to heavy burdens to individuals, families and society. Previous researches have found that though large amount of resources and great effort were devoted, no significant improvements were achieved in reducing the in-hospital mortality of AMI patients. Meanwhile, extensive studies about Chinese medicine (CM) have found that CM has special advantages in treating AMI patients. However, there is no standardized and unified clinical practice guideline (CPG) of CM for AMI. Therefore, a CPG with strict standard and generally acknowledgement is urgent to be established. This guideline was developed following the methodological process established by the World Health Organization Handbook for Guideline Development. Extensive search on clinical evidences including systematic review (SR), randomized controlled trial (RCT), observational study and case reports was launched, covering evidence of CM for AMI on several aspects, such as diagnosis, CM patterns, CM interventions on AMI and complications, cardiac rehabilitation and clinical pathway management. Besides, the application of Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach enabled the evaluation of evidence and formulation of grade of recommendation (GOR) and level of evidence (LOE). With the help of GOR and LOE, this CPG recommends the integrative CM and WM treatment method in AMI patients and provides useful information on medical decision for clinical physicians.

To observe the efficacy of cinnamaldehyde on dextran sulfate sodium(DSS)-induced ulcerative colitis(UC) with Can-dida albicans(Ca) colonization and its effect on dectin-1/TLRs/NF-κB signaling pathway in mice. C57 BL/6 mice were randomly divided into normal group, DSS group, DSS+Ca group, cinnamaldehyde group and mesalazine group. Mice in DSS+Ca group were given Ca(1×10~8 CFU per mouse) through intragastrical administration for 4 consecutive days and then distilled water with 3.0% DSS for 7 consecutive days. In cinnamaldehyde group and mesalazine group, in addition to the induction method of the DSS+Ca group, mice were given 75 mg·kg~(-1) cinnamaldehyde and 200 mg·kg~(-1) mesalazine accompanied with 3.0% DSS for 7 consecutive days, respectively. Mice in normal group and DSS group were correspondingly administered with distilled water. The general conditions of the mice were observed daily, the diseased activity index(DAI) score was calculated, and fungal loads of feces were detected by plate method. The mice were sacrificed on day 12, colon length was measured, colon mucosa damage index(CMDI) score was calculated, and histopathological analysis was carried out by HE staining. Anti-saccharomces cerevisiae antibody(ASCA) and β-1,3-glucan in serum, and TNF-α, IL-1β, IL-6, IL-8, IL-10 in serum and colon tissue were detected by ELISA. The contents of β-1,3-glucan and macrophage infiltration in colon tissues were examined by immunofluorescence staining. The protein expressions of dectin-1, TLR2, TLR4 and NF-κB were detected by Western blot and immunohistochemistry staining. The results showed that cinnamaldehyde could significantly improve the general conditions of UC mice with Ca colonization, decrease DAI and histopathological scores, reduce intestinal mucosal congestion, erosion and colon shortening, decrease Ca load in mouse feces and tissues, down-regulate the contents of ASCA and β-1,3-glucan in serum, reduce the contents of TNF-α, IL-1β, IL-6, IL-8 and increase IL-10 in serum and colon tissues, inhibit macrophages infiltration and down-regulate the protein expression of dectin-1, TLR2, TLR4 and NF-κB in colon tissue. These results suggested that cinnamaldehyde had a therapeutic effect on UC mice with Ca colonization, which might be related to the inhibition of Ca proliferation, the regulation of dectin-1/TLRs/NF-κB signaling pathways and the coordination of the balance between pro-inflammatory and anti-inflammatory factors.
Acrolein ; analogs & derivatives ; Animals ; Candida albicans ; Colitis, Ulcerative ; Colon ; Dextran Sulfate ; Disease Models, Animal ; Lectins, C-Type ; Mice ; NF-kappa B ; Signal Transduction

Objective: To investigate the neuroprotective effect of modified Yuejuwan and Ganmai Dazao Tang (YJGZ) on glutamate-induced cell injury of mouse hippocampal neuron cell line (HT22). Method: The HT22 cell was cultured aseptically, and the cell injury model was established with high concentration of glutamate acid, YJGZ aqueous extract and drug-containing serum were prepared. Then experiment was divided into normal group, model group, YJGZ drug-containing serum groups (1%, 5%, 10%), YJGZ aqueous extract group (166 mg·L^-1), and nimodipine group (100 μmol·L^-1). Methye thiazolye telrazlium (MTT) was used to detect the cell survival rate of each group, the level of lactate dehydrogenase (LDH) release and intracellular reactive oxygen species (ROS) were detected by enzyme-linked immunosorbent assay (ELISA). Western blot was used to detect the protein expression of hippocampal N-methyl-D-aspartate receptor subunit 2B protein (NR2B), cyclic adenosine response element binding protein (CREB), phosphorylated cyclic adenosine response element binding protein (p-CREB), extracellular regulated protein kinase (ERK),and phosphorylated extracellular regulated protein kinase (p-ERK). Result: As compared with normal group, the cell survival rate was significantly decreased in model group (P<0.01), LDH release rate was significantly increased (P<0.05), intracellular reactive oxygen species (ROS) level was increased (P<0.05), expression of NR2B protein was increased (P<0.05), and the protein expression levels of CREB, p-CREB, ERK and p-ERK were decreased (P<0.05). As compared with model group, YJGZ aqueous extract group and nimodipine group can significantly improve the survival rate of HT22 cells under glutamate model conditions (P<0.01), reduce cell damage, reduce LDH release rate and intracellular ROS levels (P<0.05,P<0.01), decrease the expression level of NR2B protein (P<0.05), and increase the protein expression levels of CREB, p-CREB, ERK and p-ERK (P<0.05). However, the survival rate of HT22 cells was not increased in the YJGZ-containing serum group as compared with model group. Conclusion: YJGZ aqueous extract has a significant protective effect on glutamate-induced HT22 cell injury.

Objective: Reveal the global expression profile of serum exosomal proteins of Crouzon syndrome patients. Methods: We isolated microvesicles from serum of Crouzon children with a C342Y mutation in FGFR2 by ultracentrifugation, which were further characterized by electron microscopy and immunoblotting. The protein profiling in normal subjects and Crouzon patients was systematically compared by iTRAQ proteomic analysis. Results: The result demonstrated that microvesicles were between 30—100 nm in diameter, round shape with cup-like concavity and expressed exosomal marker tumor susceptibility gene (TSG) 101 and flotillin (Flot) 1. We identified a total number of 62 proteins, among which 22 proteins overlap with ExoCarta database and were different between the Crouzon patient and the normal subject. The Ingenuity Pathway Analysis showed that the functions of these proteins are mostly involved in Developmental Disorder, Hereditary Disorder, Skeletal and Muscular Disorders, which are all related to the clinical manifestations of Crouzon syndrome. In addition, the proteins were focused on the network of "Organismal Injury and Abnormalities, Hematological System Development and Function, Cell-To-Cell Signaling and Interaction" . The central protein FN1 was presented as the key protein in the network. Conclusions Our data demonstrated that serum exosomes harbor informative proteins and FN1 was selected as a potential candidate for its role in promoting osteoblast adhesion, proliferation and mineralization.

OBJECTIVETo evaluate the effect and safety of Kuanxiong Aerosol (, KA) on patients with angina pectoris.

METHODSBlock randomization was performed to randomly allocate 750 patients into KA (376 cases) and control groups (374 cases). During an angina attack, the KA group received 3 consecutive sublingual sprays of KA (0.6 mL per spray). The control group received 1 sublingual nitroglycerin tablet (NT, 0.5 mg/tablet). Log-rank tests and Kaplan-Meier estimations were used to estimate the angina remission rates at 6 time-points after treatment (1, 2, 3, 4, 5, and >5 min). Logistic regression analysis was performed to observe the factors inflfluencing the rate of effective angina remission, and the remission rates and incidences of adverse reactions were compared for different Canadian Cardiovascular Society (CCS) classes of angina.

RESULTSThe 5-min remission rates in the KA and control groups were not signifificantly different (94.41% vs. 90.64%, P>0.05). The angina CCS class signifificantly inflfluenced the rate of remission (95% confidence interval = 0.483-0.740, P<0.01). In the CCS subgroup analysis, the 3-and 5-min remission rates for KA and NT were similar in the CCSII and III subgroups (P>0.05), while they were signifificantly better for KA in the CCSI and II subgroups (P<0.05 or P<0.01). Furthermore, the incidence of adverse reactions was signifificantly lower in the KA group than in the control group for the CCSII and III subgroups (9.29% vs. 26.22%, 10.13% vs. 20.88%, P<0.05 or P<0.01).

CONCLUSIONSKA is not inferior to NT in the remission of angina. Furthermore, in CCSII and III patients, KA is superior to NT, with a lower incidence of adverse reactions. (Registration No. ChiCTRIPR-15007204).

Aerosols ; adverse effects ; therapeutic use ; Angina Pectoris ; drug therapy ; Case-Control Studies ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Female ; Humans ; Kaplan-Meier Estimate ; Logistic Models ; Male ; Middle Aged ; Remission Induction ; Treatment Outcome

Ischemic stroke leads to high potentiality of mortality and disability.The current treatment for ischemic stroke is mainly focused on intravenous thrombolytic therapy.However,ischemia/reperfusion induces neuronal damage,which significantly influences the outcome of patients with ischemic stroke,and the exact mechanism implicated in ischemia/reperfusion injury remains unclear,although evidence shows that oxidative stress is likely to be involved.Betulinic acid is mainly known for its anti-tumor and anti-inflammatory activities.Our previous study showed that betulinic acid could decrease the reactive oxygen species (ROS) production by regulating the expression of NADPH oxidase.Thus,we hypothesized that betulinic acid may protect against brain ischemic injury in the animal model of stroke.Focal cerebral ischemia was achieved by using the standard intraluminal occlusion method and reperfusion enabled after 2 h ischemia.Neurological deficits were scored.Infarct size was determined with 2,3,5-triphenyltetrazolium chloride monohydrate (TTC) staining and the mRNA expression of NADPH oxidase 4 (NOX4) was determined by RT-PCR in infarct tissue.ROS generation and apoptosis in ischemic tissue were analyzed by measuring the oxidative conversion of cell permeable 2',7'-dichloro-fluorescein diacetate (DCF-DA) to fluorescent dichlorofluorescein (DCF) in fluorescence microplate reader and TUNEL assay,respectively.In Kunming mice,2 h of middle cerebral artery (MCA) occlusion followed by 24 or 72 h of reperfusion led to an enhanced NOX4 expression in the ischemic hemisphere.This was associated with elevated levels of ROS generation and neuronal apoptosis.Pre-treatment with betulinic acid (50 mg/kg/day for 7 days via gavage) prior to MCA occlusion prevented the ischemia/reperfusion-induced up-regulation of NOX4 and ROS production.In addition,treatment with betulinic acid could markedly blunt the ischemia/reperfusion-induced neuronal apoptosis.Finally,betulinic acid reduced infarct volume and ameliorated the neurological deficit in this stroke mouse model.Our results suggest that betulinic acid protects against cerebral ischemia/reperfusion injury in mice and the down-regulation of NOX4 may represent a mechanism contributing to this effect.

The aim of the study is to evaluate the utility value of species identification of Triculinae based on COI gene.Triculinae-like samples were collected from different places in Fujian Province.After classification based on morphology characters,genomic DNA was extracted from collected samples.Then the segments of COI gene were amplified and sequenced for taxonomy annotation and phylogenetic analysis.Eleven samples were annotated as Gammatricula (identities:88.96％-97.82％),the other two were annotated as Tricula wumingensis (identity:87.08％) and Neotricula apart (identity:88.55％),respectively.In most cases (12 out of 13),there was a difference between results based on different classification methods on a genus level.The alignment of COI gene segment is sufficient for preliminary identification of Triclulinae at family level.However,it is need further study in species identification of Triclulinae at genus level.