This study aims to explore the pharmacodynamic material basis of Jinbei Oral Liquid(JBOL) against idiopathic pulmonary fibrosis(IPF) based on serum pharmacochemistry and network pharmacology. The ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technology was employed to analyze and identify the components absorbed into rat blood after oral administration of JBOL. Combined with network pharmacology, the study explored the pharmacodynamic material basis and potential mechanism of JBOL against IPF through protein-protein interaction(PPI) network construction, "component-target-pathway" analysis, Gene Ontology(GO) functional enrichment, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. First, a total of 114 compounds were rapidly identified in JBOL extract according to the exact relative molecular mass, fragment ions, and other information of the compounds with the use of reference substances and a self-built compound database. Second, on this basis, 70 prototype components in blood were recognized by comparing blank serum with drug-containing serum samples, including 28 flavonoids, 25 organic acids, 4 saponins, 4 alkaloids, and 9 others. Finally, using these components absorbed into blood as candidates, the study obtained 212 potential targets of JBOL against IPF. The anti-IPF mechanism might involve the action of active ingredients such as glycyrrhetinic acid, cryptotanshinone, salvianolic acid B, and forsythoside A on core targets like AKT1, TNF, and ALB and thereby the regulation of multiple signaling pathways including PI3K/AKT, HIF-1, and TNF. In conclusion, JBOL exerts the anti-IPF effect through multiple components, targets, and pathways. The results would provide a reference for further study on pharmacodynamic material basis and pharmacological mechanism of JBOL.
Drugs, Chinese Herbal/pharmacokinetics* ; Animals ; Tandem Mass Spectrometry ; Network Pharmacology ; Rats ; Chromatography, High Pressure Liquid ; Rats, Sprague-Dawley ; Male ; Idiopathic Pulmonary Fibrosis/metabolism* ; Humans ; Administration, Oral ; Protein Interaction Maps/drug effects* ; Signal Transduction/drug effects*

OBJECTIVE: To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS). METHODS: In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4. RESULTS: Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group. CONCLUSIONS In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.

Aim To explore the effects of NaAsO

OBJECTIVE Compound Kushen injection (CKI) is a bis-herbal formulation extracted from Kushen (Radix Sophorae Flavescentis) and Baituling (Rhizoma Heterosmilacis Japonicae). Clinically, it is used as the adjuvant treat?ment of cancer. However, with the increased application, the cases of immediate hypersensitivity reactions (IHRs) also gradually rise. In this study, we investigated the underlying mechanism(s) and active constituent(s) for CKI-induced IHRs in experimental models. METHODS T helper 2 (Th2) immunity-amplified mice were prepared by aluminum adjuvant. Anaphylactic shock was detected by measuring rectal thermometry in propranolol pretreated mice. For evaluating micro?vascular permeability, Evans blue extravasation assay was used. Platelet-activating factor (PAF), serum total IgE (tIgE) and mouse mast cell protease 1 (MMCP1) were measured by ELISA. RESULTS The obtained results showed that CKI did not elevate serum tIgE and MMCP1 after consecutive immunization for five weeks, but could induce Evans blue extravasation (local) and cause obvious hypothermia (systemic) after a single injection. Further study showed that alka?loids in Kushen, especially matrine, were responsible for CKI-induced IHRs. Mechanism study showed that various PAF receptor antagonists could significantly counter CKI-induced IHRs locally or systemically. In cell system, CKI was able to promote PAF production in a non-cell-selective manner. In cell lysate, the effect of CKI on PAF production became stron?ger and could be abolished by blocking de novo pathway. CONCLUSION In conclusion, our study identifies, for the first time, that CKI is a PAF inducer. It causes non-immunologic IHRs, rather than IgE-dependent IHRs, by promoting PAF production through de novo pathway. Alkaloids in Kushen, especially matrine, are the prime culprits for IHRs. Our find?ings may provide a potential approach for preventing and treating CKI-induced IHRs.

Eight full-length genes of an avian influenza virus Chinese isolate of H9N2 subtype, A/Chicken/Guangdong/HL/2006 (H9N2) (abbreviated as Ck/GD/HL/06), were amplified by RT-PCR, including the 5' and 3' non-coding region. All the genes were cloned and sequenced. The phylogenetic analysis results showed the HA gene of Ck/GD/HL/06 was located in the same phylogenetic clade as Dk/HK/Y280/97 (H9N2), while the Dk/HK/Y280/97-like viruses had been predominately isolated from chickens in mainland China. After the analysis of glycosylation sites and receptor-binding sites in the HA, it was shown that the HA of Ck/GD/HL/06 exhibited the common feature of H9 subtype avian influenza virus isolated from China, but the leucine (Leu) residue at the amino acid position 226 indicated the potential of binding with SA alpha,2-6 receptor. The three internal genes of Ck/GD/HL/06 (PB1, PA and NP) had the highest nucleotide identity with A/Viet Nam/1203/2004 (abbreviated A/VN/1203/04) isolate, which was shown to be transmitted from chickens to human and caused lethal infection in human. No analogous H9N2 strains was reported in previous studies. Based on the high similarity of Ck/GD/HL/06 three genes to A/VN/1203/04, it was suggested that the possibility of generating new highly pathogenic H5N1 AIVs by recombination was worthy of our attention. Further studies should be needed for molecular epidemiologic surveillance of H9N2 AIV in the south China for a long time.
Amino Acid Sequence ; Animals ; Chickens ; China ; Cloning, Molecular ; Evolution, Molecular ; Genes, Viral ; genetics ; Genomics ; Influenza A Virus, H9N2 Subtype ; genetics ; isolation & purification ; Influenza in Birds ; virology ; Phylogeny ; Polymerase Chain Reaction ; Sequence Alignment ; Sequence Analysis, DNA ; Sequence Homology, Nucleic Acid ; Viral Proteins ; chemistry ; genetics

BACKGROUNDA comparison of efficacy and safety between transradial and transfemoral approach for percutaneous coronary intervention (PCI) in bifurcations has not been done. This study evaluated feasibility of transradial PCI (TRI) and compared the immediate and followup results with transfemoral PCI (TFI) in bifurcations.

METHODSOne hundred and thirty-four consecutive patients with bifurcations were treated with PCI in our hospital from April 2004 to October 2005. Of these, there were 60 patients (88 lesions) in TRI group and 74 patients (101 lesions) in TFI group. Bifurcations type was classified according to the Institut Cardiovasculaire Paris Sud Classification.

RESULTSTRI group had smaller stent diameter ((3.06 +/- 0.37) mm vs (3.18 +/- 0.35) mm, P = 0.023) and postprocedural in-stent minimum lumen diameter ((2.62 +/- 0.37) mm vs (2.74 +/- 0.41) mm, P = 0.029) than TFI, but there were not significant differences in in-stent subacute thrombosis rate (0% vs 1.0%, P = 0.349), target lesion revascularization (TLR) (0% vs 1.0%, P = 0.349) following procedure and thrombosis (2.3% vs 1.0%, P = 0.482), in-stent restenosis (12.5% vs 10.9%, P = 0.731), in-segment restenosis (17.0% vs 14.9%, P = 0.681), TLR (10.2% vs 13.9%, P = 0.446) and TLR-free cumulative survival rate (89.8% vs 86.1%, P = 0.787) at seven months followup. No death was reported in the two groups.

CONCLUSIONTransradial intervention is feasible and appears to be as effective and safe as transfemoral PCI in treatment of true bifurcational lesions.

Adult ; Aged ; Angioplasty, Balloon, Coronary ; adverse effects ; methods ; Coronary Angiography ; Coronary Disease ; therapy ; Drug Delivery Systems ; Female ; Femoral Artery ; Humans ; Male ; Middle Aged ; Radial Artery

BACKGROUNDThe sirolimus and paclitaxel distribution patterns and tissue residence time may be modified in atherosclerotic lesions for patients with diabetes, and the biological mechanisms of action for these agents differ significantly. Previous clinical trials have yielded discrepant results of major adverse cardiac events and restenosis between a sirolimus-eluting stent and a paclitaxel-eluting stent in coronary artery disease. Therefore, this study was conducted to compare in-hospital and long-term clinical outcomes between patients receiving sirolimus-eluting stent (Cypher or Cypher Select stent) and paclitaxel-eluting stent (Taxus Express stent) after percutaneous intervention (PCI) in Chinese patients with diabetes.

METHODSOne hundred and sixty-four consecutive diabetic patients underwent PCI in Fuwai Hospital from April 2004 to December 2004. Of them, 101 patients received Cypher or Cypher Select stents (Cypher group, 145 stents) and 63 patients received Taxus Express stents (Taxus group, 129 stents). Repeat coronary angiography was performed at 6-month and clinical outcomes were evaluated at 1- and 3-year follow-up. Stent thrombosis was classified according to Academic Research Consortium (ARC).

RESULTSThe two groups did not differ significantly with respect to cardiac death, recurrent myocardial infarction (re-MI), target vessel revascularization (TVR) and occurrence of major adverse cardiac events (MACE). And the MACE-free cumulative survival at 1- and 3-year follow-up and early, late and very late thrombosis rates were also similar in the two groups (all P > 0.05). There was a trend favoring PES over SES with regard to reducing cardiac death (0 vs 2.0%, P = 0.524), re-MI (0 vs 2.0%, P = 0.524), the composite of the cardiac death and re-MI (0 vs 4.0%, P = 0.299) and very late thrombosis (0 vs 3.0%, P = 0.295) between 1-year and 3-year follow-up.

CONCLUSIONThe study indicates that PCI with either Cypher or Taxus stents is associated with similar efficacy and safety in the small population of Chinese diabetic patients during long-term follow-up.

Aged ; Asian Continental Ancestry Group ; statistics & numerical data ; China ; Coronary Angiography ; Coronary Artery Disease ; diagnostic imaging ; therapy ; Diabetes Complications ; diagnostic imaging ; therapy ; Diabetes Mellitus ; ethnology ; pathology ; physiopathology ; Drug-Eluting Stents ; Female ; Follow-Up Studies ; Humans ; Inpatients ; statistics & numerical data ; Male ; Middle Aged ; Survival Analysis ; Time Factors ; Treatment Outcome

OBJECTIVETo probe the efficacy and feasibility of the transradial approach for diagnostic coronary angiography with 5F universal catheter.

METHODSTransradial coronary angiography was performed in 3094 consecutive patients, 2396 men and 698 women, aged 30 - 81 years, mean age (56.1 +/- 9.8) years, from July 2000 to April 2004. Patients were divided into 5F improved Terumo catheter group (improved Terumo group, n = 985), 5F universal Terumo catheter group (Terumo group, n = 1024) and 5F universal Medtronic catheter group (Medtronic group, n = 1085). The procedure success rate, duration of operation and fluoroscopy between groups were compared.

RESULTSThe procedure success rate was 98.4% in improved Terumo group, 98.0% in Terumo group, and 96.0 % in Medtronic group, respectively. The success rate was higher in improved Terumo group than in Medtronic group (P < 0.05). The average duration of operation and fluoroscopy in improved Terumo group was (17.9 +/- 5.8) min and (4.8 +/- 1.8) min, in Terumo group was (18.2 +/- 5.5) min and (5.0 +/- 1.7) min, but (21.1 +/- 7.2) min and (5.2 +/- 1.9) min in Medtronic group. There were significant differences among group (P < 0.05).

CONCLUSIONS(1) Transradial coronary angiography with small diameter universal catheter is safe and easy to perform with a higher success rate and allow earlier patient ambulation, and should be strongly encouraged and recommended. (2) Option of angiographic catheter plays a key role in the safety, efficacy and quality of transradial coronary angiography. Seemingly, the improved Terumo group was excellent and shoud be popularized.

Adult ; Aged ; Aged, 80 and over ; Cardiac Catheterization ; methods ; Coronary Angiography ; methods ; Female ; Humans ; Male ; Middle Aged ; Radial Artery ; diagnostic imaging