OBJECTIVE To study the efficacy of Tianjiang xueshuantong pills in the treatment of coronary heart disease. METHODS In accordance with the common pathogenesis of coronary heart disease， acute myocardial ischemia model， hyperlipidemia model， blood stasis model， and carotid artery thrombosis model were established using Wistar rats or SD rats as the experimental subjects. The effects of Tianjiang xueshuantong pills administered at high， medium， and low doses （0.6， 1.2 and 2.4 g/kg） on hemodynamic parameters and myocardial enzyme markers [lactate dehydrogenase （LDH）， creatine kinase-MB （CK- MB）]， oxidative stress factors [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione （GSH）]， inflammatory cytokines [tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， IL-1β， monocyte chemotactic protein-1 （MCP-1）， intercellular adhesion molecule-1 （ICAM-1）]， myocardial infarction percentage， serum lipid indexes [total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）]， platelet aggregation function 话：022-84845240。E-mail：jiangx@tjipr.com [maximum aggregation rate （MAR）]， and thrombus formation indexes [thrombosis time， thrombus mass， thrombus protein content， plasminogen activator inhibitor-1 （PAI-1）， and tissue-type plasminogen activator （t-PA）] were evaluated in the rat models. RESULTS In myocardial ischemia tests， Tianjiang xueshuantong pills significantly reduced the percentage of myocardial infarction and the levels of CK-MB， LDH， MDA， GSH， IL-6， TNF-α， IL- 1β， and MCP-1 in serum （P＜0.05 or P＜0.01）. In hyperlipidemia tests， high dose of Tianjiang xueshuantong pills significantly reduced the serum levels of TC， LDL and significantly increased the level of HDL in rats after 2 weeks and 4 weeks of administration. In blood stasis tests， different doses of Tianjiang xueshuantong pills significantly reduced MAR of rats （P＜0.01）. In artery thrombosis tests， high dose of Tianjiang xueshuantong pills significantly prolonged the time of thrombosis formation （P＜ 0.01）， significantly reduced the weight and protein content of thrombus and the level of PAI-1 in serum （P＜0.01）. CONCLUSIONS Tianjiang xueshuantong pills exert therapeutic effects on coronary heart disease through multi-dimensional synergistic actions， including anti-myocardial ischemia， lipid-lowering， and anti-thrombotic effects.

The chemical constituents from the fruits of Morinda citrifolia were systematically explored by chromatographic fractionation methods including silica gel, octadecylsilyl(ODS) gel, Sephadex LH-20 gel, and preparative high performance liquid chromatography(pre-HPLC). The chemical structures of all isolated compounds were identified on the basis of their physicochemical properties, spectroscopic analyses, as well as the comparisons of their physicochemical and spectroscopic data with the reported data in literature. As a result, 22 isolated compounds from the 90% ethanol extract of the fruits of M. citrifolia were identified, which were moricitritone(1), 2'-deoxythymidine(2), cyclo-(L-Pro-L-Tyr)(3), methyl-5-hydroxy-2-pyridinecarboxylate(4), methyl pyroglutamate(5), bisbenzopyran(6), epipinoresinol(7), 3, 3'-bisdemethyl pinoresinol(8), 3, 3'-bisdemethyltanegool(9), trimesic acid(10), crypticin B(11), kojic acid(12), vanillic acid(13), protocatechoic acid(14), 5-hydroxymethyl furfural(15), blumenol A(16), 1-O-(9Z, 12Z-octadecadienoyl) glycerol(17), mucic acid dimethylester(18), methyl 2-O-β-D-glucopyranosylbenzoate(19), 2-phenylethyl-O-β-D-glucoside(20), scopoletin(21), and quercetin(22). Among them, compound 1 was a new pyrone derivative, compounds 2, 4-7, 10-12, and 17 were isolated from the plants belonging to Morinda genus for the first time, and compound 18 was obtained from M. citrifolia for the first time. Moreover, on the basis of testing the activities of all isolated compounds on inhibiting the proliferation of synovial fibroblasts in vitro by MTS assay, the anti-rheumatoid arthritis activities of all isolated compounds were initially evaluated. The results showed that compounds 1-6, 9, 19, and 20 exhibited remarkable anti-rheumatoid arthritis activities, which displayed the inhibitory effects on the proliferation of MH7A synovial fibroblast cells with the IC_(50) values in the range of(3.69±0.08) to(168.96±0.98) μmol·L~(-1).
Fruit/chemistry* ; Morinda/chemistry* ; Synoviocytes ; Cell Proliferation ; Arthritis

In order to improve the management level of medicine list of medical institutions in China ，and help medical institutions build a medicine list of medical institutions with reasonable drug use structure ，standardized adjustment procedures ， convenient operation and application and scientific evaluation methods ，so as to meet the needs of clinical rational drug use to the greatest extent ，with the support of the Pharmaceutical Care Professional Committee of the Chinese Pharmaceutical Association ， China-Japan Friendship Hospital and the First Affiliated Hospital of University of Science and Technology of China （Anhui Provincial Hospital ）jointly initiate and complete Guideline for the Evaluation of Medicine List in Chinese Medical Institutions jointly with a number of medical institutions. In strict accordance with the methodological requirements of World Health Organization standard guidelines ，based on the Delphi method ，the guideline formulation working group has constructed the quality evaluation index system and quantitative scoring table of medicine list management in medical institutions from the 5 dimensions of organization and management ，structure，adjustment，application and e valuation of the list. It is used to help medical institutions evaluate the quality of their medicine list management ，so asto play a positive role in the fine management of medicine list in medical institutions.

The chemical constituents from the branches and leaves of Artocarpus incisus were isolated and purified via silica gel, ODS, and Sephadex LH-20 column chromatography as well as preparative HPLC. The chemical structures of all isolated compounds were identified in the light of their physicochemical properties, spectroscopic analyses, and comparisons of their physicochemical and spectroscopic data with the reported data in literature. As a result, 20 compounds were isolated and characterized from the 90% ethanol extract of the branches and leaves of A. incisus, which were identified as tephrosin(1), 6-hydroxy-6 a, 12 a-dehydrodeguelin(2), sarcolobin(3), lupiwighteone(4), 12-deoxo-12α-methoxyelliptone(5), 6 aα,12 aα-12 a-hydroxyelliptone(6), homopterocarpin(7), 3-hydroxy-8,9-dimethoxypterocarpan(8), pterocarpin(9), maackiain(10), medicarpin(11), calycosin(12), genistein(13), formononetin(14), 5-hydroxy-4',7-dimethoxy isoflavone(15), liquiritigenin(16), 4(15)-eudesmene-1β,7α-diol(17), ent-4(15)-eudesmene-1β,6α-diol(18), 1α-hydroxyisodauc-4-en-15-al(19), and guaianediol(20). Except compounds 13 and 16, all other compounds were isolated from the Artocarpus plants for the first time. Additionally, using MTS assay, compounds 1-20 were eva-luated for their anti-rheumatoid arthritis activities by measuring their anti-proliferative effects on synoviocytes in vitro. As a consequence, compounds 1-16 showed notable anti-rheumatoid arthritis activities, which displayed inhibitory effects on the proliferation of MH7 A synovial fibroblast cells, with the IC_(50) values in range of(9.86±0.09)-(218.07±1.96) μmol·L~(-1).
Arthritis ; Artocarpus ; Cell Proliferation ; Ethanol ; Genistein ; Plant Extracts/pharmacology* ; Silica Gel ; Synoviocytes

Objective:To analyze the characteristics of clinical distribution and change of aeroallergens in children with allergic diseases from 2015 to 2020.Methods:Children who visited Capital Institute of Pediatrics affiliated Children′s Hospital, suspected of allergic diseases and received serum aeroallergens specific immunoglobulin E (sIgE) test were retrospectively enrolled (1 to 14 years old). sIgE was detected by Phadia1000 system with radioallergosorbent test fluorescent enzyme-linked immunoassay. The characteristics and change of the aeroallergens among the 6 years was analyzed. Enumeration data were expressed by percentage and categorical variables were compared by the independent samples t-test and Pearson χ 2 test. Results:In total 4 608 tests (4 575 patients) of children were enrolled, the average age was (5.4±2.9) years old, with the median age of 5.0 years old. 3 176 were boys (68.9%), and 1 432 were girls (31.1%). 4 294 children were from the north of China (93.2%), 295 children were from the south of China (6.4%), and 19 children were from unknown regions (0.4%). In total the most common aeroallergen was mold mixture (1 956/4 457 tests, 43.9%) and Alternaria alternata (276/630 tests, 43.8%), followed by Artemisia (300/889 tests, 33.7%), Humulus scandens (12/38 tests, 31.6%) and grass mixture (909/2 874 tests, 31.6%). Among the 6 years, mold, grass pollen and tree pollen sensitization increased, and mold [38/130 (29.2%) vs 1 574/3 233 (48.7%)], grass pollen [11/77 (14.3%) vs 1 069/3 072 (34.8%)] increased significantly (χ 2 was 18.953 and 49.559, respectively, P=0.000). Positive rate of tree pollen increased [1/10 (10.0%) vs 516/2 122 (24.3%)], but did not have statistical significance (χ2=1.111, P=0.292). Dust mite [36/146 (24.7%) vs 321/1 408 (22.8%)] and hair of pets [7/33 (21.2%) vs 321/1 408 (17.1%)] sensitization didn′t change greatly (χ 2 =0.258, P =0.611; χ 2 =0.379, P =0.538). In 2015, the most common aeroallergens was mold (38/130, 29.2%), followed by dust mite (36/146, 24.7%), while in 2020, the most common aeroallergens was still mold (1 574/3 233, 48.7%), with grass pollen (1 069/3 072, 34.8%) and tree pollen (516/2 122, 24.3%) ranked after. Conclusion:Mold might be the most common aeroallergens in allergic children in Beijing area. With time went on, dust mite was gradually exceeded by grass pollen and tree pollen.

Objective:To analyze the characteristics of clinical distribution and change of aeroallergens in children with allergic diseases from 2015 to 2020.Methods:Children who visited Capital Institute of Pediatrics affiliated Children′s Hospital, suspected of allergic diseases and received serum aeroallergens specific immunoglobulin E (sIgE) test were retrospectively enrolled (1 to 14 years old). sIgE was detected by Phadia1000 system with radioallergosorbent test fluorescent enzyme-linked immunoassay. The characteristics and change of the aeroallergens among the 6 years was analyzed. Enumeration data were expressed by percentage and categorical variables were compared by the independent samples t-test and Pearson χ 2 test. Results:In total 4 608 tests (4 575 patients) of children were enrolled, the average age was (5.4±2.9) years old, with the median age of 5.0 years old. 3 176 were boys (68.9%), and 1 432 were girls (31.1%). 4 294 children were from the north of China (93.2%), 295 children were from the south of China (6.4%), and 19 children were from unknown regions (0.4%). In total the most common aeroallergen was mold mixture (1 956/4 457 tests, 43.9%) and Alternaria alternata (276/630 tests, 43.8%), followed by Artemisia (300/889 tests, 33.7%), Humulus scandens (12/38 tests, 31.6%) and grass mixture (909/2 874 tests, 31.6%). Among the 6 years, mold, grass pollen and tree pollen sensitization increased, and mold [38/130 (29.2%) vs 1 574/3 233 (48.7%)], grass pollen [11/77 (14.3%) vs 1 069/3 072 (34.8%)] increased significantly (χ 2 was 18.953 and 49.559, respectively, P=0.000). Positive rate of tree pollen increased [1/10 (10.0%) vs 516/2 122 (24.3%)], but did not have statistical significance (χ2=1.111, P=0.292). Dust mite [36/146 (24.7%) vs 321/1 408 (22.8%)] and hair of pets [7/33 (21.2%) vs 321/1 408 (17.1%)] sensitization didn′t change greatly (χ 2 =0.258, P =0.611; χ 2 =0.379, P =0.538). In 2015, the most common aeroallergens was mold (38/130, 29.2%), followed by dust mite (36/146, 24.7%), while in 2020, the most common aeroallergens was still mold (1 574/3 233, 48.7%), with grass pollen (1 069/3 072, 34.8%) and tree pollen (516/2 122, 24.3%) ranked after. Conclusion:Mold might be the most common aeroallergens in allergic children in Beijing area. With time went on, dust mite was gradually exceeded by grass pollen and tree pollen.

Objective　To investigate the role of fatty acid binding protein 4 (FABP4) in the apoptosis of mouse podocytes induced by hyperhomocysteinemia (HHcy).　Methods　Nine wild male C57BL/6J mice (Cbs+/+) and nine C57BL/6J male mice with cystathionine beta synthase gene knockout heterozygote (Cbs+/-) were used as the control group and HHcy model group, respectively. All mice were fed with 2% high methionine diet for 8 weeks to replicate the HHcy model. The ultrastructure of glomerular podocytes was observed by transmission electron microscopy. Glomerular podocytes were cultured in vitro and divided into blank control group (Control group) podocytes treated with Hcy concentration of 0 μmol•L-1 for 48 hours. The podocytes of homocysteine group (Hcy group) were treated with Hcy concentration of 80 μmol•L-1 for 48 hours. Podocytes were infected with GFP-labeled adenovirus (Ad-GFP group) and FABP4 overexpression adenovirus (Ad-FABP4 group), respectively. Podocytes were treated with Hcy and FABP4 adenovirus, named as Hcy+Ad-FABP4 group. The expression of FABP4 was detected by qRT-PCR and Western blot. The changes of apoptosis-related proteins Bax, Bcl-2 and Caspase-12 were analyzed by Western blot. The apoptosis rate of cells was measured by flow cytometry.　Results　Compared with the control group, the podocyte injury was aggravated and accompanied by the increasing number of apoptotic cells in the kidney tissues of model group mice. At the same time, the expression of FABP4 mRNA (3.20±0.42) and protein (4.98±1.12) in model group were higher than those in control group (2.09±0.13, 3.04±0.11)(P<0.05). The expression of FABP4 mRNA (5.34±0.28) and the expression of FABP4 protein (11.94±0.22) in Hcy group were higher than those in control group (4.00±0.17, 5.10±0.20)(P<0.05). After infection with FABP4 adenovirus, the mRNA expression levels (3.05±0.22) and protein expression (4.07±0.20) of FABP4 in Ad-GFP group were not significantly different from those in control group (3.07±0.15, 3.93±0.15) (P>0.05); the mRNA expression levels (4.59±0.28) and protein expression (10.07±0.82) of FABP4 in Ad-FABP4 group were higher than those in Ad-GFP group (P<0.05). Bax/Bcl-2 value (3.15±0.65) and Caspase-12 protein expression (4.30±0.89) in Hcy group were higher than those in control group (2.19±0.10, 3.19±0.47) (P<0.05). The Bax/Bcl-2 values (5.42±0.55) and Caspase-12 protein expression (7.87±1.27) in the Hcy+Ad-FABP4 group were significantly higher than those in the Hcy+Ad-GFP group (3.19±0.47, 4.34±0.64) (P<0.05).　FABP4 plays an important role in the apoptosis of mouse podocytes induced by HHcy. Flow cytometry analysis showed that the total apoptotic rate of Hcy group was (10.85±1.25) higher than that of control group (3.77±0.12) (P<0.05). Hcy + Ad-FABP4 group (15.72±1.60) was higher than that of Hcy+Ad-GFP group (11.22±0.43) (P< 0.05).　Conclusion　FABP4 promotes the apoptosis of podocytes in mice treated with HHcy.

BACKGROUNDThe acute myeloid leukemia 1 (AML1)-eight-twenty-one (ETO) fusion protein generated by the t(8;21)(q22;q22) translocation is considered to display a crucial role in leukemogenesis in AML. By focusing on the anti-leukemia effects of eyes absent 4 (EYA4) gene on AML cells, we investigated the biologic and molecular mechanism associated with AML1-ETO expressed in t(8;21) AML.

METHODSQualitative polymerase chain reaction (PCR), quantitative reverse transcription PCR (RT-PCR), and Western blotting analysis were used to observe the mRNA and protein expression levels of EYA4 in cell lines. Different plasmids (including mutant plasmids) of dual luciferase reporter vector were built to study the binding status of AML1-ETO to the promoter region of EYA4. Chromatin immunoprecipitation assay was used to study the epigenetic silencing mechanism of EYA4. Bisulfite sequencing was applied to detect the methylation status in EYA4 promoter region. The influence of EYA4 gene in the cell proliferation, apoptosis, and cell clone-forming ability was detected by the technique of Cell Counting Kit-8, flow cytometry, and clonogenic assay.

RESULTSEYA4 gene was hypermethylated in AML1-ETO+ patients and its expression was down-regulated by 6-fold in Kasumi-1 and SKNO-1 cells, compared to HL-60 and SKNO-1-siA/E cells, respectively. We demonstrated that AML1-ETO triggered the epigenetic silencing of EYA4 gene by binding at AML1-binding sites and recruiting histone deacetylase 1 and DNA methyltransferases. Enhanced EYA4 expression levels inhibited cellular proliferation and suppressed cell colony formation in AML1-ETO+ cell lines. We also found EYA4 transfection increased apoptosis of Kasumi-1 and SKNO-1 cells by 1.6-fold and 1.4-fold compared to negative control, respectively.

CONCLUSIONSOur study identified EYA4 gene as targets for AML1-ETO and indicated it as a novel tumor suppressor gene. In addition, we provided evidence that EYA4 gene might be a novel therapeutic target and a potential candidate for treating AML1-ETO+ t (8;21) AML.

Apoptosis ; genetics ; physiology ; Blotting, Western ; Cell Line, Tumor ; Cell Proliferation ; genetics ; physiology ; Chromatin Immunoprecipitation ; Core Binding Factor Alpha 2 Subunit ; genetics ; metabolism ; DNA Methylation ; genetics ; Epigenesis, Genetic ; genetics ; Gene Silencing ; HL-60 Cells ; Humans ; Leukemia, Myeloid, Acute ; genetics ; metabolism ; pathology ; Oncogene Proteins, Fusion ; genetics ; metabolism ; RNA, Small Interfering ; genetics ; RUNX1 Translocation Partner 1 Protein ; Radioimmunoprecipitation Assay ; Trans-Activators ; genetics ; metabolism

BACKGROUNDTwo recent whole-exome sequencing researches identifying somatic mutations in the ubiquitin-specific protease 8 (USP8) gene in pituitary corticotroph adenomas provide exciting advances in this field. These mutations drive increased epidermal growth factor receptor (EGFR) signaling and promote adrenocorticotropic hormone (ACTH) production. This study was to investigate whether the inhibition of USP8 activity could be a strategy for the treatment of Cushing's disease (CD).

METHODSThe anticancer effect of USP8 inhibitor was determined by testing cell viability, colony formation, apoptosis, and ACTH secretion. The immunoblotting and quantitative reverse transcription polymerase chain reaction were conducted to explore the signaling pathway by USP8 inhibition.

RESULTSInhibition of USP8-induced degradation of receptor tyrosine kinases including EGFR, EGFR-2 (ERBB2), and Met leading to a suppression of AtT20 cell growth and ACTH secretion. Moreover, treatment with USP8 inhibitor markedly induced AtT20 cells apoptosis.

CONCLUSIONSInhibition of USP8 activity could be an effective strategy for CD. It might provide a novel pharmacological approach for the treatment of CD.

Adrenocorticotropic Hormone ; metabolism ; Animals ; Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; physiology ; Cell Survival ; drug effects ; physiology ; Endopeptidases ; metabolism ; Endosomal Sorting Complexes Required for Transport ; antagonists & inhibitors ; metabolism ; Enzyme Inhibitors ; pharmacology ; Humans ; Indenes ; pharmacology ; Mice ; Pyrazines ; pharmacology ; Receptor, Epidermal Growth Factor ; metabolism ; Ubiquitin Thiolesterase ; antagonists & inhibitors ; metabolism

OBJECTIVETo investigate the clinical effect and application value of the modified method of prepuce-degloving repair (PDR) in the treatment of urethrocutaneous fistula (UCF) following hypospadias surgery.

METHODSWe retrospectively analyzed 87 cases of UCF caused by hypospadias repair from May 2001 to December 2011, of which 61 were treated by simple closure or Y-V plasty of the fistula (group A), and the other 26 by modified PDR (group B). We compared the success rate of surgery and long-term recurrence between the two groups.

RESULTSThe total success rates of repair were 78.7 and 96.2% in groups A and B, respectively. Thirteen cases in group A did not respond to surgery, of which 6 failed to be cured by the second operation but later were treated successfully by modified PDR. In comparison, there was only 1 case of failure in group B, which was cured by a second PDR.

CONCLUSIONModified PDR can significantly improve the success rate and reduce the recurrence rate of UCF after hypospadias surgery, which deserves wide clinical application.

Child ; Child, Preschool ; Foreskin ; surgery ; Humans ; Hypospadias ; surgery ; Male ; Reconstructive Surgical Procedures ; methods ; Retrospective Studies ; Treatment Outcome ; Urinary Fistula ; etiology ; surgery ; Urologic Surgical Procedures, Male