Evaluation of metoprolol standard dosing pathway in Chinese patients with acute coronary syndrome: a prospective multicenter single-arm interventional study / 老年心脏病学杂志（英文版）

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.

The Relationship between the Expressions of CD33 and CD13 and the Prognosis of Patients with Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the expressions of CD33 and CD13 in newly diagnosed multiple myeloma (MM) patients and its relationship with prognosis.@*METHODS@#It was retrospectively observed that the expression of CD33 and CD13 in 121 MM patients who were newly diagnosed from January 2014 to January 2020, and the relationship between the expressions of CD33 and CD13 and patients prognosis was analyzed.@*RESULTS@#Among the 121 newly diagnosed MM patients, there were 30 patients (24.8%) in the CD33+ group and 12 patients (9.9%) in the CD13+ group. Kaplan-Meier analysis showed that, compared with the CD33- group, the progression-free survival (PFS) time and overall survival (OS) time were significantly shortened in MM patients in CD33+ group (PFS 17.5 vs 23 months, P=0.000; OS 18.5 vs 25 months, P=0.000); and the PFS time and OS time of MM patients in the CD13+ group were also significantly shortened than those in CD13- group (PFS 21 vs 22 months, P=0.012; OS 25 vs 26 months, P=0.006). Cox regression analysis showed that CD33 and CD13 were independent adverse prognostic factors in MM patients (CD33: P=0.000;CD13: P=0.003).@*CONCLUSION@#CD33 and CD13 are prognostic risk factors in patients with MM.

To Explore Mechanism of Xinmaikang Tablets in Treatment of Atherosclerosis Cardiovascular Disease Based on Network Pharmacology and Cell Experiment / 中国实验方剂学杂志

ObjectiveTo investigate the potential pharmacological mechanism of Xinmaikang tablets in the treatment of atherosclerosis cardiovascular disease by using network pharmacology and cell experimental validation. MethodThe components of Xinmaikang tablets were searched by BATMAN-TCM database and the active ingredients and potential targets were screened. The atherosclerosis related disease targets were searched in GeneCards and online mendelian inheritance in man（OMIM） disease databases. The therapeutic targets were obtained by mapping the intersection of the tablets and disease targets. Therapeutic targets were uploaded to STRING database to construct protein-protein interaction（PPI） network. Cytoscape software was used to create a "drug-active component-therapeutic target" network map， and a network topology algorithm was used to screen key action targets. David software was used for gene ontology（GO） and Kyoto encyclopedia of genes and genomes（KEGG） function enrichment analysis. The key targets of drug therapy were validated by in vitro cell assay. ResultA total of 19 active ingredients， 132 potential targets and 4703 atherosclerotic disease-related target genes of Xinmaikang tablets were retrieved and screened， and 84 intersection targets were obtained. 3 key therapeutic targets of Xinmaikang tablets in the treatment of atherosclerotic diseases were screened， including Calmodulin 1（CALM1）， voltage-dependent L-type calcium channel subunit alpha-1C（CACNA1C） and Phosphatidylinositol 4，5-bisphosphate 3-kinase catalytic subunit alpha isoform（PIK3CA）. A total of 313 biological processes， 89 molecular functions and 53 cell components were obtained by GO enrichment. A total of 40 pathways were obtained from KEGG functional enrichment， including purine metabolism， renin secretion， CGMP/PKG signaling pathway and so on. In vitro cell experiment results verified that Xinmaikang tablets can up-regulate the expression of CALM1 and CACNA1C， down-regulate the expression of PIK3CA， so as to inhibit the activity of inflammatory response， and play a therapeutic role in atherosclerotic diseases. ConclusionXinmaikang tablets may treat atherosclerosis cardiovascular disease through betulin， methyleugenol and other compounds， through purine metabolism， renin secretion， cGMP/PKG signaling pathway and other pathways， which acts on CALM1， CACNA1C， PIK3CA and other targets.

Expressions of CD96 and CD123 and Their Relationship with Prognosis of Patients with Myelodysplastic Syndrome / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the relationship between expression of CD96 and CD123 and prognosis of patients with myelodysplastic syndrome(MDS).</p><p><b>METHODS</b>Eight-nine MDS patients(MDS group) and 20 persons without hematologic disease as controls(Control group) were enrolled. The patients were grouped by the risk. All participants received bone marrow biopsy. Mononuclear cells were extracted, CD34CD38CD123and CD34CD38CD96cells were counted by using flow cytometry. Expressions of 2 type cells in control group, MDS group and its subgroups were analyzed.</p><p><b>RESULTS</b>The proportion of CD34cells and CD34CD38cells in mononuclear cells of patients in MDS group was higher than in control group (P<0.05). The proportions of CD34CD38CD123cells and CD34CD38CD96cells in CD34CD38cells were significantly higher than that in control group(P<0.05) and the proportion increased with the risk. In the low-and middle-risk group, the rates of complete remission(CR) and partial remission(PR) of patients with CD123and CD96were higher than those in patients with CD123and CD96; in the middle-2 and high risk patients, the PR of patients with CD123was higher than that in patients with CD123(P<0.05). The CR rate of patients with CD96was higher than that of patients with CD96(P<0.05).</p><p><b>CONCLUSION</b>The differentiation of CD34cells in bone marrow of MDS patients is abnormal, and the high expression of CD123 and CD96 cells existes. These findings may partially explain the cause of hematopoietic stem cell malignant clone in MDS patients.</p>

Effects of Uric Acid on Expression of Lysyl Oxidase and Matrix Metalloproteinase-2 in Rat Smooth Muscle Cells / 中国循环杂志

Objectives: To explore the effects of uric acid on expression of lysyl oxidase (LOX) and matrix metalloproteinase-2 (MMP-2) in rat vascular smooth muscle cells. Methods: Rat vascular smooth muscle cell was cultured, and divided into following groups: control group, uric acid group (cells were treated with 20, 40, 60 mg/L uric acid for 48 hours, cells were treated with 40 mg/L uric acid for 24, 48, 72 h) and β-aminopropionitrile group (cells were treated with 10 mg/ml β-aminopropionitrile for 24 hours). The reactive oxygen species was detected by confocal microscopy. mRNAs and protein expression levels of LOX and MMP-2 in rat vascular smooth muscle cells were measured by RT-PCR and Western blot, respectively. Results: The number of increased cell proliferation, reactive oxygen species burst, mRNAs and protein expression levels of LOX and MMP-2 were significantly increased in uric acid group than in control group (P<0.01). The mRNAs and protein expression levels of LOX and MMP-2 were significantly downregulated in β-aminopropionitrile group than in uric acid group (P<0.01). Conclusions: Uric acid can enhance the expression of LOX and MMP-2 in rat vascular smooth muscle cells.

Biosorption characteristics of ectomycorrhizal fungal mycelium for anthracene / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the potential of Gomphidius viscidus, a kind of ectomycorrhizal fungi, for phytoremediation of anthracene in soil.</p><p><b>METHODS</b>Absorptioe changes of micro-habitat were studied in detail.</p><p><b>CONCLUSION</b>Ectomycorrhizal plants have a strong potential for remediation of polycyclic aromatic hydrocarn characteristics of both active and inactivated mycelia.</p><p><b>RESULTS</b>A high calculated adsorption capacity of 1,886.79 mg/g and 1,515.15 mg/g at 25 °C, pH 6.0 for active and inactivated mycelia respectively, was obtained based on Langmuir model. The ANT biosorption was more ideally characterized by the Langmuir model than by the Freundlich model. The biosorption of anthracene to biomass was extremely fast and could be modeled with pseudo-second order adsorption kinetics. Moreover, ectomycorrhizal mycelia demonstrated a strong ability to adjust the physiological process to get adapted to the change of micro-habitat.</p>

Clinicopathologic features of peripheral T-cell lymphoma, unspecified with follicular pattern / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features of peripheral T-cell lymphoma, unspecified (PTL-U) with follicular pattern.</p><p><b>METHODS</b>The clinical data, hematoxylin and eosin-stained sections of lymph node biopsies and follow-up data of 18 cases of PTL-U associated with follicular growth pattern were reviewed and studied. Eight cases of reactive lymphoid hyperplasia were used as controls. Semi-quantitative observation by retiform micrometer rule was carried out. Immunohistochemical study was also performed in all cases. T-cell receptor and immunoglobulin heavy chain gene rearrangement studies were conducted by polymerase chain reaction-based method.</p><p><b>RESULTS</b>The median age of the patients was 53 years. The male-to-female ratio was 1.57:1 in lymphoma group. All of the lymphoma patients presented with superficial lymphadenopathy, with (8/18) or without B symptoms. Histologically, the lymphoma was characterized by follicles of various sizes and shapes. The T zones were expanded by medium-sized lymphoma cells which contained clear cytoplasm and irregular nuclei. Mitotic figures were commonly identified. Immunohistochemical study confirmed that the lymphoma cells were of T-lineage. The proliferative index, as highlighted by Ki-67, was higher [average = (38.24 +/- 13.42)%/mm2] than that in the control group. T-cell receptor gene rearrangement was demonstrated in 71.4% (10/14) of the lymphoma cases.</p><p><b>CONCLUSIONS</b>A definitive diagnosis of PTL-U with follicular pattern can be made on the basis of morphologic examination, immunohistochemical assessment and clinical features. Cases with atypical features can further be delineated by molecular analysis. Long-term follow up of these patients is prudent.</p>

A clinico-pathological analysis of HCV infection in post-liver transplantation patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the pathological characteristics of HCV infection after liver transplantation.</p><p><b>METHODS</b>This is a retrospective analysis of the clinico-pathological changes of 73 liver biopsies obtained from 61 patients who had HCV infection (including HCV recurrence and reinfection) after liver transplantation in our center from September 2000 to September 2006.</p><p><b>RESULTS</b>Abnormal enzyme test results due to HCV infection happened on the 9th to the 1553rd post-transplantation surgery day. The serum HCV RNA level was higher than 10(5) copies/ml in 19 cases and between 10(2)-10(5) copies/ml in the other 42 cases. The histological changes in the transplanted livers were hepatocellular degeneration, necrosis and apoptosis, portal infiltrations and fibrosis. They were classified into two stages (early stage and late stage) according to the onset of fibrosis which appeared within 90 days or later after their transplantation in our study. The incidence of predominant portal infiltrates and liver fibrosis in early stage and late stage was 5.7% (2/35) and 94.7% (36/38) (chi2=54.34, P<0.01) and 2.9% (1/35) and 97.4% (37/38) (chi2=61.47, P<0.01) respectively.</p><p><b>CONCLUSIONS</b>Pathological features of early stage and late stage hepatitis C infection in transplanted livers are different and they are also different from that in native livers. Liver biopsies are important in clinical staging, evaluation of the severity, and differential diagnosis of post-transplantation HCV infection.</p>

Clinicopathological analysis of biliary tract complications on post-liver transplantation patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To analyze the pathohistological changes of the livers and the clinical features of patients with biliary tract complications after their orthotopic liver transplantations.</p><p><b>METHODS</b>From Sept 1998 to June 2005 clinical and pathological data of 173 post-liver transplantation patients with biliary tract complications were analyzed.</p><p><b>RESULTS</b>Biliary tract complications occurred within 3-2920 days after the transplantation operations. These complications occurred within 1-30 days, 31-90 days, 91-180 days, 180 days at rates of 49.71%, 17.92%, 4.62%, 27.74% respectively. The complications were of inflammatory nature in 171 cases, (72.25%), and of obstructive nature in 164 cases (27.74%). The main pathological changes were epithelium degeneration of interlobular bile ducts, inflammatory cell infiltration in portal areas, proliferation of interlobular bile ducts, fibrosis in portal areas, cholestasis in small bile ducts and hepatocytes.</p><p><b>CONCLUSION</b>Many of the biliary tract complications of post-liver transplantation in our cases were of inflammatory nature and they often occurred within 30 days after the surgery. Obstructive nature complications often occurred in 90 days after the surgery and the prognosis of these cases was much poorer. The pathological changes of live tissues shown in liver biopsies are important for prognostic evaluation, differential diagnosis and categorization of biliary tract complications.</p>

Six Months Follow Up Results of "Granulocytes-Colony Stimulating Factor" Based Stem Cell Therapy in Patients with Myocardial Infarction: MAGIC Cell Randomized Controlled Trial

BACKGROUND AND OBJECTIVES: Granulocytes-colony stimulating factor (G-CSF) has a stem cell mobilizing capacity and favorable effects on ventricular remodeling following a myocardial infarction. G-CSF based stem cell therapy has shown favorable results in animal studies. However, the long term outcome of G-CSF based stem cell therapy in clinical trial remains unknown. Herein, we report the six month follow up results of two different G-CSF based stem cell therapy strategies. SUBJECTS AND METHODS: We compared the intra-coronary infusion of mobilized peripheral blood stem cells (PBSCs) with G-CSF (n=10), mobilization with G-CSF alone (n=16) and control percutaneous coronary intervention (PCI) alone (n=15) in patients following a myocardial infarction. RESULTS: At the six month follow up evaluations, the intra-coronary cell infusion was found to have improved the left ventricular (LV) systolic function and remodeling compared to the baseline, whereas G-CSF alone showed no improvement. Therefore, an intra-coronary cell infusion showed better improvements in the LV systolic function (p<0.001) and remodeling (p<0.01) than G-CSF alone. Cell infusion also showed better results than the control PCI alone group, but these did not reach statistical significance with the limited number of patients used in this study. Patients who received G-CSF administration showed a modest increase of binary restenosis (p=0.185) and a greater late loss in the minimal luminal diameter at the 6 month follow up than the control group. CONCLUSION: An intra-coronary cell infusion of mobilized PBSCs using G-CSF was found to be better than G-CSF alone at the six month follow up evaluation. G-CSF was also found to increase the potential risk of restenosis, especially when administered prior to stent implantation. The efficacy of an intra-coronary infusion of mobilized PBSCs should be evaluated in a large randomized controlled trial.

Pathologic feature and diagnosis of pulmonary alveolar proteinosis / 中华病理学杂志

<p><b>OBJECTIVE</b>To describe the pathologic features and diagnostic algorithm of pulmonary alveolar proteinosis (PAP).</p><p><b>METHODS</b>Thirty-nine biopsy and postmortem cases of PAP were studied by light microscopy and histochemical staining using periodic acid-Schiff (with digestion) (PAS-D), mucicarmine (with digestion) (mucicarmine-D) and alcian blue.</p><p><b>RESULTS</b>Histologically, the affected lung tissue displayed the following characteristic features: (1) alveoli and some of the small bronchioles were filled with eosinophilic and fine granular proteinaceous material with needle-like clefts; (2) proteinaceous material was seen admixed with various numbers of degenerated and sometimes exfoliated pneumocytes; (3) pneumocytes were hyperplastic; (4) alveolar capillaries and alveolar septa had become hyperemic, but pulmonary interstitial inflammation was not obvious; (5) no significant inflammation was identified in the bronchial wall; (6) compensating emphysema was noted in the surrounding lung parenchyma. Fragments of eosinophilic, finely granular proteinaceous material with needle-like clefts were also found in the bronchoalveolar lavage fluid under light microscopy. The proteinaceous material was stained red by PAS-D. The staining for mucicarmine-D was negative, while alcian blue staining was either weakly positive (faint blue staining) or negative. Pathologic examination of lung biopsies and bronchoalveolar lavage fluid thus remaines the gold standard for diagnosis of PAP.</p><p><b>CONCLUSIONS</b>Identification of homogeneous, eosinophilic, finely granular and PAS-D-positive proteinaceous material with needle-like clefts in alveolar spaces or bronchoalveolar lavage fluid is of diagnostic importance in PAP. Bronchoalveolar lavage, being a relatively safe and non-invasive procedure, can be a useful adjunct in arriving at the final conclusion.</p>

Pathologic diagnosis of 1123 post-transplant liver biopsies from 665 liver transplant patients / 中华病理学杂志

<p><b>OBJECTIVE</b>To summarize the Chinese experience in pathologic diagnosis of liver biopsies after orthotopic liver transplantation (OLTx).</p><p><b>METHODS</b>1123 post-transplant liver biopsies from 665 OLTx patients from the Shanghai Eastern Hepatobiliary Surgery Hospital, Tianjin First Central Hospital, Guangzhou Sun Yat-sen University and Chongqing Southwest Hospital were retrospectively analyzed. All liver biopsies were stained with hematoxylin and eosin. Immunohistochemical studies for cytomegalovirus, HBsAg, CK19, CD4 and CD8 were also performed in selected examples.</p><p><b>RESULTS</b>In the involved hospitals, 4 to 12 types of complications were encountered after OLTx. The number of liver biopsies performed for each patient ranged from 1 to 9 (mean = 2.2). The timing of these biopsies varied from the second to the 2877 th post-transplant day. The 5 most common complications were acute cellular rejection (35.6%), ischemic-reperfusion injury (13.4%), biliary stricture (5.6%), drug complication (5.0%) and chronic rejection (4.7%). The 5 earliest complications after OLTx were primary non-function (occurring at day 4.7 +/- 2.1), ischemic-reperfusion injury (occurring at day 14.0 +/- 4.0), acute cellular rejection (occurring at day 32.1 +/- 62.9), hepatic artery thrombosis / stricture (occurring at day 62.9 +/- 74.2) and cytomegalovirus infection (occurring at day 107.7 +/- 93.0).</p><p><b>CONCLUSIONS</b>This study has evaluated the types, incidence and timing of major complications occurring after OLTx. The most important issue is the distinction between rejection and non-rejection pathology. Thorough understanding of atypical pathologic features of these complications is necessary. The Banff Schema (rejection activity index) for grading liver allograft rejection is useful for monitoring anti-rejection therapy and should be used routinely.</p>

NF-kappa B decoy potentiates the effects of radiation on vascular smooth muscle cells by enhancing apoptosis

NF-kappa B promotes cell survival against external stress such as radiation. We examined whether NF-kappa B decoy transfection enhances the antiproliferative effects of radiation on vascular smooth muscle cells (VSMCs) in vitro. The irradiation induced activation or nuclear translocation of NF-kappa B p65 in VSMCs was confirmed by immunofluorescence. NF-kB decoy transfection resulted in inhibition of the radiation-induced NF-kB activation in VSMCs and the subsequent reduction of transcription and translocation of ICAM, iNOS, and TNF-alpha, downstream molecules under the control of NF-kappa B. By using MTT assay, NF-kappa B decoy augmented the antiproliferative effects of radiation, where the effect of low dose radiation (2 and 8-Gy) of the cells transfected with NF-kappa B decoy was equivalent to the high dose (16-Gy) irradiated non-transfected cells at 48 h after irradiation: 1.06+/-0.16, 1.11+/-0.22, 1.20+/-0.25, respectively. The decrease in proliferation and survival of the radiation treated cells by flow cytometry analysis showed that NF-kappa B inhibition did not show any additive effects on the cell cycle of the irradiated VSMCs, while apoptosis was significantly increased after NF-kappa B decoy transfection in the irradiated VSMCs (apoptosis fraction: 13.33+/-2.08% vs. 26.29+/-7.43%, for radiation only vs. radiation+NF-kappa B decoy transfection, P < 0.05). In addition, at 48 h, NF-kappa B decoy transfection dose dependently (10 mM vs. 20 mM) inhibited proliferation of 16Gy-irradiated VSMCs, and showed greater antiproliferative efficacy than 100 mM sulfasalazine, a specific NF-kappa B inhibitor. These results indicate that NF-kappa B inhibition reduces proliferation and survival of irradiated VSMCs, likely by increased apoptosis rather than additive cell cycle arrest and suggest the possibility of adjunctive gene therapy using NF-kappa B decoy to improve efficacy and to decrease the adverse effects of intracoronary radiation therapy.

Relationship of Polymorphisms in the Oxidative Stress Related Genes - Paraoxonase and p22phox - to Variant Angina and Coronary Artery Stenosis in Korean

BACKGROUND AND OBJECTIVES: Oxidative stress plays an important role in the pathogenesis of coronary atherosclerosis and spasm. We investigated whether the polymorphisms in two oxidative stress-related genes, paraoxonase and p22phox, are associated with risks of coronary artery spasm and stenosis. SUBJECTS AND METHODS: The study comprised of 116 patients with variant angina, 118 patients with coronary artery stenosis and 117 control subjects, who were all classified by coronary angiography. In all three groups, the genotype frequencies of the Q192R polymorphism of the paraoxonase gene and C242T polymorphism of the p22phox gene were analyzed, and the serum thiobarbituric acid-reactive substance concentrations measured. RESULTS: The frequency of the RR genotype of the paraoxonase Q192R polymorphism was significantly higher in patients with variant angina and coronary artery stenosis than in the control subjects (40.4% in variant angina and 37.8% in coronary artery stenosis vs. 24.7% in control, p=0.020 and 0.048, respectively). From the multivariate analysis, the odds ratio of the RR genotype was 2.240 for variant angina (95% confidence interval ; 1.012-4.956), and 2.333 for coronary artery stenosis (95% confidence interval ; 1.140-4.777), in relation to the control subjects. The thiobarbituric acid-reactive substance level was significantly higher in the RR type than in the QQ+QR types (RR vs. QQ+QR : 1.106+/-0.420 nmol/mL vs. 0.949+/-0.311 nmol/mL, p=0.028). There was no significant difference in the prevalence of the C242T polymorphism of the p22phox gene between the three groups. CONCLUSION: The RR genotype of the paraoxonase gene Q192R polymorphism was found to be an independent risk factor for both coronary spasm and stenosis.

Role of 5-HT2A Receptor Gene T102C Polymorphism in Coronary Artery Disease and Serum Lipid Level

BACKGROUND AND OBJECTIVES: The 5-HT2A receptor is one of the main mediators of a serotonin-evoked coronary artery contraction. This is because vasoconstriction is selectively blocked by the 5-HT2 receptor antagonist, with the 5-HT2A receptor gene mRNA being detected in spastic coronary arteries. The relationship between the T102C polymorphism of the 5-HT2A receptor gene and the response to the 5-HT2A antagonist (clozapine) has recently been established, suggestive of a functional implication. Previous studies have observed an association between low cholesterol levels and mental disorders, but the underlying cause has not been determined. It has been established that the T102C polymorphism of the 5-HT2A serotonin receptor gene and a variety of psychological problems are related, but the relationship between the serum lipid level and this genetic polymorphism has not been reported. We investigated the influence of this polymorphism on coronary artery disease, including vasospastic angina and the clinical parameters, such as the lipid profile. SUBJECTS AND METHODS: After a diagnostic angiography was performed, the genotype was identified from the genomic DNA extracted from the peripheral blood of 646 patients without specific psychiatric diseases. RESULTS: There were no differences in the genotype frequencies between coronary artery disease, coronary artery disease with vasospasm, and the normal control groups, even from a subgroup analysis of the clinical parameters. Contrary to previous reports, the genotype distribution was not related to a myocardial infarction or hypertension. The lipid profile analysis showed significantly lower total cholesterol (193.5 vs. 202.1mg/dL, p=0.016) and HDL-cholesterol (42.7 vs. 46.2mg/dL, p=0.003) levels in the CC genotype than the other genotypes, and the frequencies of CC genotype showed a significantly decreasing trend between the HDL-cholesterol (p=0.003) and total cholesterol (p=0.003) quartiles. From a multivariate analysis, only the HDL-cholesterol level was significantly associated with a lower frequency of the CC genotype (p=0.006). CONCLUSION: The T102C polymorphism is not related to coronary artery disease, including vasospasm of the coronary artery, but the CC genotype of this polymorphism is related to low HDL-cholesterol. We identified a novel genetic polymorphism of the serotonin receptor, which affects the HDL-cholesterol level. Because previous observational studies have shown an association between low cholesterol levels and mental disorders, our data should be considered when analyzing the serum lipid levels and serotonin receptor function in humans.

Long-term toxicity test of rhIL-11 in cynomolgus / 第二军医大学学报

Objective:To investigate the long-term toxicity of recombinant human interleukin-11(rhIL-11) in cynomolgus. Methods: Eighteen cynomolgus were randomized into 4 groups: control group(2/sex), low dose group(2/sex), medium dose group(2/sex)， and high dose group(3/sex). The drug groups were sc adminstered 0.1, 0.3 and 1.0 mg/kg of rhIL-11 for 90 days with a 30-day recovery period. The clinical signs were observed, electrocardiogram, hematological, biochemical, urinary and immunological parameters were measured, organ masses were weighed, bone marrow and pathological histology were observed. Results: The food consumption, body mass of the drug groups were decreased, the body temperature was increased transiently. One of the low dose group showed restricted movements and tremors. One of the high dose group vomited and another died. Reduced red blood cell(RBC) count, hemoglobin(Hb) concentration, hematocrit(Hct), mean corpuscular volume(MCV), mean corpuscular hemoglobin(MCH), and mean corpuscular hemoglobin concentration(MCHC), dose-related increase of platelet(Plat) counts were present in drug groups. Biochemical examinations revealed dose-related decreases in serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), lactate dehydrogenase(LDH), total proteins(TP) and albumin(Alb) increases in serum alkaline phosphatase(ALP) levels. Positive antibody responses were seen and circulatory immune complex(CIC) was significantly increased in all drug groups. Hypertropy of marrow megakaryocyocytes was noted in the medium and high dose groups. The heart and liver masses were slightly increased in all treatment groups. Treatment-related microscopic findings included dose-related degeneration in the liver and the kidney. The adverse effects were reversed by the end of the recovery period. Conclusion: The target organs and systems are blood, liver, kidney, immmue system and bone marrow. The toxicity injuries were reversible and the no-toxic-effect level is 0.1 mg/kg.

Long-term toxicity test of rhIL-11 in cynomolgus / 第二军医大学学报

Objective:To investigate the long-term toxicity of recombinant human interleukin-11(rhIL-11) in cynomolgus. Methods: Eighteen cynomolgus were randomized into 4 groups: control group(2/sex), low dose group(2/sex), medium dose group(2/sex)， and high dose group(3/sex). The drug groups were sc adminstered 0.1, 0.3 and 1.0 mg/kg of rhIL-11 for 90 days with a 30-day recovery period. The clinical signs were observed, electrocardiogram, hematological, biochemical, urinary and immunological parameters were measured, organ masses were weighed, bone marrow and pathological histology were observed. Results: The food consumption, body mass of the drug groups were decreased, the body temperature was increased transiently. One of the low dose group showed restricted movements and tremors. One of the high dose group vomited and another died. Reduced red blood cell(RBC) count, hemoglobin(Hb) concentration, hematocrit(Hct), mean corpuscular volume(MCV), mean corpuscular hemoglobin(MCH), and mean corpuscular hemoglobin concentration(MCHC), dose-related increase of platelet(Plat) counts were present in drug groups. Biochemical examinations revealed dose-related decreases in serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), lactate dehydrogenase(LDH), total proteins(TP) and albumin(Alb) increases in serum alkaline phosphatase(ALP) levels. Positive antibody responses were seen and circulatory immune complex(CIC) was significantly increased in all drug groups. Hypertropy of marrow megakaryocyocytes was noted in the medium and high dose groups. The heart and liver masses were slightly increased in all treatment groups. Treatment-related microscopic findings included dose-related degeneration in the liver and the kidney. The adverse effects were reversed by the end of the recovery period. Conclusion: The target organs and systems are blood, liver, kidney, immmue system and bone marrow. The toxicity injuries were reversible and the no-toxic-effect level is 0.1 mg/kg.