Expression of TPX2 in kidney renal clear cell carcinoma and its clinical significance / 国际肿瘤学杂志

Objective:To analyze the expression of targeting protein for Xklp2 (TPX2) in kidney renal clear cell carcinoma (KIRC) and its clinical significance.Methods:The postoperative tissue samples of 54 patients with KIRC admitted to the Department of Urology, the First Affiliated Hospital of Bengbu Medical College from July 2017 to June 2019 were collected. Immunohistochemistry was used to detect the protein expression of TPX2 in renal carcinoma and paracancerous tissues. The difference of TPX2 mRNA expression between KIRC tissues and normal tissues was analyzed by using the TIMER database, which verified the immunohistochemical results. The UALCAN database and the Kaplan-Meier plotter database were used to analyze the relationship between TPX2 mRNA expression and clinical stage, molecular subtypes, lymph node metastasis, and prognosis of patients with KIRC. The protein interaction network was constructed by STRING database to obtain TPX2-related proteins, and the genes corresponding to the related proteins were enriched for the KEGG pathway. The relationship between TPX2 expression and immune cell infiltration and the immune checkpoint was studied by using the TIMER database.Results:Immunohistochemical results showed that the positive expression rate of TPX2 protein was 48.15% (26/54) in cancer tissues, which was higher than that in paracancerous tissues (20.37%, 11/54) ( χ2=9.25, P=0.002). The results of bioinformatics analysis showed that TPX2 mRNA expression was significantly up-regulated in KIRC [cancer tissue: 1.89 (1.49, 2.42), normal tissue: 0.35 (0.24, 0.57), U=2 297.00, P<0.001]. The expression of TPX2 mRNA was related to the clinical stage ( χ2=34.36, P<0.001), molecular subtypes ( χ2=30.15, P<0.001), and lymph node metastasis status ( χ2=27.21, P<0.001) of KIRC patients. The 5-year survival rate (53.80%) in patients with high TPX2 expression was lower than that in patients with low TPX2 expression (74.40%, χ2=18.87, P<0.001). STRING database protein interaction network construction obtained 20 TPX2-related proteins, and the genes corresponding to the related proteins were enriched in the cell cycle. The expression of TPX2 was positively correlated with B cells ( r=0.30, P<0.001), CD8 + T cells ( r=0.23, P<0.001), CD4 + T cells ( r=0.18, P<0.001), macrophages ( r=0.20, P<0.001), neutrophils ( r=0.31, P<0.001), dendritic cells ( r=0.39, P<0.001) infiltration and most of its biomarkers (all P<0.05). It was positively correlated with immune checkpoint PD-1 ( r=0.31, P<0.001) and CTLA-4 ( r=0.27, P<0.001), but not correlated with PD-L1 ( r=0.07, P=0.146) . Conclusion:TPX2 is highly expressed in KIRC and is closely associated with poor prognosis. It is expected to be a new therapeutic target for KIRC.

Investigation of Laboratory and Clinical Feature in the Patients with Myeloproliferative Neoplasm Co-expression of BCR-ABL1 and JAK2 V617F / 中国实验血液学杂志

OBJECTIVE@#To analyze the comprehensive laboratory test data of BCR-ABL1 fusion gene and JAK2 V617F mutation co-expressed in myeloproliferative neoplasm (MPN) patients, and investigate its relative clinical significance.@*METHODS@#Data of 1 332 MPN patients were comprehensively analyzed, BCR-ABL1 (P190/P210/P230) fusion gene and JAK2 V617F mutation were detected by real time-polymerase chain reaction (RT-PCR) technique, the CALR, MPL, JAK2 12 and 13 exon mutations were detected by the First Generation Sequencing, the bone marrow cell morphology and pathological characteristics were evaluated by bone marrow smear and biopsy technique, the immune phenotypes of bone marrow cells were evaluated by flow cytometry, the chromosome karyotypes of bone marrow cells were analyzed by chromosome G banding technique.@*RESULTS@#Four of the 1 332 patients were found to have the co-existence of BCR-ABL1 fusion gene and the JAK2 V617F mutation, with a 0.3% incidence and a median age of 70 years old, including 2 cases of polycythemia vera, 1 case of primary myelofibrosis, and 1 case of chronic myeloid leukemia-accelerated phase. The clues of double positive genes of such patients at the time of initial diagnose could not be cued only by age, physical signs and cell morphology, they should be analyzed by comprehensive test data.@*CONCLUSION@#The co-existence of BCR-ABL1 fusion gene and JAK2 V617F mutation in the same case is a kind of disease with special clinical significance. The application of multiple detection methods can improve the detection of this disease, which is conducive to early detection, reasonable diagnosis and treatment by clinicians.

Impact of Myocardial Infarction and Abnormalities of Cardiac Conduction System on Sudden Cardiac Death / 法医学杂志

Sudden cardiac death （SCD）, most commonly seen in coronary heart disease, is a kind of sudden death caused by series of cardiac parameters, which usually combines with myocardial infarction. However, some SCDs （including early myocardial infarction） happen suddenly and cause death in a very short time. In these circumstances, typical morphological changes are lack in macroscopic or microscopic fields, which make such SCDs become the emphasis and difficulty in the present research. SCD caused by myocardial infarction and abnormalities of cardiac conduction system （CCS） is related to atherosclerosis of coronary artery closely. This paper reviews cardiac dysfunction caused by myocardial infarction and diseases of CCS from morphology and molecular biology, and explores potential relationship between them. This paper aims to provide clues to the mechanism of myocardial infarction related sudden death and possible assistance for forensic diagnosis of SCD.

Risk factors for recurrent wheezing in infants and young children suffering from dust mite allergy after their first wheezing / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the risk factors for recurrent wheezing in infants and young children suffering from dust mite allergy after their first wheezing.</p><p><b>METHODS</b>A total of 1 236 infants and young children who experienced a first wheezing episode and were hospitalized between August 2014 and February 2015 were enrolled, among whom 387 were allergic to dust mites. These infants and young children were followed up to 1 year after discharge. A total of 67 infants and young children who experienced 3 or more recurrent wheezing episodes within 1 year were enrolled as the recurrent wheezing group, while 84 infants and young children who did not experience recurrent wheezing during follow-up were enrolled as the control group. Univariate analysis and multivariate logistic stepwise regression analysis were performed to investigate the risk factors for recurrent wheezing in these patients.</p><p><b>RESULTS</b>The univariate analysis showed that the age on admission, wheezing time before admission, Mycoplasma pneumoniae infection rate, and influenza virus infection rate were associated with recurrent wheezing. The multivariate logistic stepwise regression analysis showed that the older age on admission (OR=2.21, P=0.04) and Mycoplasma pneumoniae infection (OR=3.54, P=0.001) were independent risk factors for recurrent wheezing.</p><p><b>CONCLUSIONS</b>Infants and young children who are allergic to dust mites, especially young children, have a significantly increased risk of recurrent wheezing if they are complicated by Mycoplasma pneumoniae infection during the first wheezing episode.</p>

Studying the changes of the related serum complement immune indexes in patients with occupational medicamentosa-like dermatitis induced by trichloroethylene and workers occupationally exposed to trichloroethylene / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To explore the mechanism of occupational medicamentosa-like dermatitis (OMDT) induced by trichloroethylene (TCE) and some immunity indexes in workers occupationally exposed to TCE.</p><p><b>METHODS</b>The blood samples from 8 cases with medicamentosa-like dermatitis in 1st, 2nd, 3rd, 4th and 5th weeks after admitting to hospital were examined for liver function, immunoglobulin and some complement indexes. Thirty nine workers occupationally exposed to TCE were investigated for urinary TCE and some immuno-complement indexes. The TCE concentrations of air in workplaces were monitored.</p><p><b>RESULTS</b>C3d-CIC and C3 of patients before admission were (92.86 ± 44.80) mg/L and 0.91 ± 0.19 mg/L, respectively. C3d-CIC and C3 of patients before discharge were (52.41 ± 17.75) mg/L and (1.14 ± 0.22) mg/L, respectively. There were significant differences between admission and discharge (P < 0.05). The average TCE concentration in 4 workplaces was (351.96 ± 36.72) mg/m(3), which was higher than the occupational exposure limits (OELs). The number of workers exposed to the TCE concentration-time weighted and TCA in urine over OELs were 28.21% and 56.41% of total subjects, respectively. The serum IgG and CIC levels of patients before discharge were (10.03 ± 1.21) mg/L and 103.50 ± 29.17 mU/L, which were significantly lower than those (17.21 ± 1.85) mg/L and (227.46 ± 111.67) mU/L of patients before admission (P < 0.01).</p><p><b>CONCLUSION</b>The type II and III hypersensitivity may be associated with OMDT and the organ injure induced by TCE.</p>

Mutation of drug resistant gene in HIV/AIDS patients with antiretroviral therapy in Shandong province in 2011 / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate drug resistance status in patients with highly active antiretroviral therapy (HAART) in Shandong province.</p><p><b>METHODS</b>A total of 758 patients were separated from the anticoagulatory whole blood during May and October in 2011. The entire protease gene and part of the reverse transcriptase gene were amplified by RT-PCR and nest-PCR in the samples with viral load larger than 1000 copies/ml, then sequenced the gene fragments. Mutation of drug resistant gene and drug susceptibility was analyzed by the online tool HIV db program developed by Stanford University.</p><p><b>RESULTS</b>The rate of virologic failure in patients was 9.1% (69/758). A total of 53 gene sequences that acquired were used for genotypic resistance analysis. A total of 23 patients were indicated drug resistance with the total of 3.1% (23/742). Drug resistance rates of nucleotide reverse transcriptase inhibitor (NRTI) and non-NRTI(NNRTI) were 2.4% (18/742) and 3.0% (22/742), respectively, and the primary mutation types of drug resistance were M184V and Y181C for NRTI and NNRTI, with no resistance to protease inhibitor (PI). In the 23 patients indicated drug resistance, 78.3% (18/23) were NRTI resistance, 95.7% (22/23) were NNRTI resistance and 73.9% (17/23) dual NRTI and NNRTI resistance.</p><p><b>CONCLUSION</b>The presence of drug resistant gene in HIV strains among AIDS patients with HAART in Shandong province was at low level, but mutation diversity was found in drug resistant gene.</p>

The prevalence and evolution of HIV drug-resistant strains in people who live with HIV/AIDS during HIV antiretroviral therapy in Shandong province / 中华预防医学杂志

<p><b>OBJECTIVE</b>To understand the prevalence and evolution of HIV drug-resistant strains in people who live with HIV/AIDS (PLWHA) during HIV antiretroviral therapy in Shandong province.</p><p><b>METHODS</b>Viral load testing was performed by using fluorescence real-time quantitative PCR (NucliSens EasyQ system) on 324 patients who were under HIV antiretroviral therapy (ART) over 1 year in Shandong province. HIV resistance testing was conducted on the samples with more than 1000 copies/ml by using genotypic resistance testing method established in our lab. We tested the samples from drug-resistant patients before and after treatment to analyze the evolution of HIV resistant strains.</p><p><b>RESULTS</b>The resistance rate for the patients under HIV ART over 1 year was 6.2% (20/324). The rate of drug-resistant mutation, but not resistant to ART was 0.6% (5/324). Nucleoside reverse transcriptase inhibitor (NRTIs) and non-NRTIs (NNRTIs) accounted for 93.1% (94/101) and protein inhibitors (PIs) accounted only 6.9% (7/101) of all mutations. M184V (48.0%, 12/25) and Y181C (32.0%, 8/25) were the most frequent mutations among 25 samples. Our research showed 20.0% (2/10) patients were resistant to primary ART and 1 patient was detected drug resistance in 6 months after ART treatment. HIV evolved from wild type to drug resistant virus, from low level to high level drug resistance, and from resistance to few to multiple drugs. In addition, interactions between mutations may influence the sensitivity of patients to other drug treatment.</p><p><b>CONCLUSION</b>The prevalence of HIV drug-resistant strains in Shandong province is still at a low level, but its evolution is complex.</p>

Analysis of condom use and its factors on female sex workers in Shandong province / 中华预防医学杂志

<p><b>OBJECTIVE</b>This study was to investigate the condom use and its factors on sex workers in Shandong province, and to provide effective suggestions for AIDS prevention strategies and interventions.</p><p><b>METHODS</b>From April to July in 2009, 4732 female sex workers were investigated through anonymous questionnaires from 11 cities which were selected based on the AIDS epidemic, geographic location, economic conditions in Shandong province. Serum samples were collected and antibodies were tested by ELISA and TPPA from 4641 people.</p><p><b>RESULTS</b>4732 female sex workers who were 15 - 58 years old were investigated and the majority belonged to the low age group (≤ 24 years old) which accounted for 61.5% (2912/4732). Among the 4732 female sex workers, the unmarried, the divorced, or the widowed females accounted for 72.8% (3441/4725) and 72.0% (3403/4726) of them were poorly educated.42.3% (1994/4719) of them were found from other provinces. The right answers for knowledge of AIDS accounted for 45.7% (2164/4732). 80.6% (3416/4236) of these females were found to used condoms in the most recent commercial sex activity. The rate of consistently using condoms in sex activity during the last month was 58.4% (2467/4221). In this survey, 7.3% (337/4637) of investigated females had been diagnosed with sexually transmitted diseases, 30.7% (1449/4726) of them had received HIV antibody test, 70.4% (3323/4732) of these people had received the AIDS intervention services, and 3.6% (167/4668) of them had ever used drug. Multivariate logistic regression analysis showed that high education level (junior high school or lower vs senior high school or higher, adjusted OR = 0.77, 95%CI: 0.67 - 0.90), having received the HIV intervention (received vs unreceived, adjusted OR = 1.36, 95%CI: 1.17 - 1.58), antibody detection (done vs not done, adjusted OR = 1.33, 95%CI: 1.15 - 1.55), and good knowledge about AIDS (low score group vs high score group, adjusted OR = 0.37, 95%CI: 0.32 - 0.44) were independent factors that increased safe sex behavior; while using drug (drug vs not drug, adjusted OR = 0.22, 95%CI: 0.15 - 0.31) was a negative factor.</p><p><b>CONCLUSION</b>The prevalence rate of HIV infection among female sex workers was low in Shandong province. However, the low rate of condom use and the high prevalence of self-reported STD-related symptoms suggested that more attentions should be paid to the factors of risk behaviors, and more targeted interventions are critically needed.</p>

Atorvastatin use and coronary flow reserve in patients with coronary slow flow / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the impact of statin use on coronary flow reserve (CFR) in patients with slow coronary flow.</p><p><b>METHODS</b>A total of 91 patients with chest pain and coronary slow flow but normal coronary angiography were included in this study, patients were divided into statin group (atorvastatin 20 mg/d for 8 weeks, n = 51) and non-statin group (n = 40), 26 healthy subjects with normal angiography and negative exercise ECG test served as normal controls. Blood cholesterol was measured. Doppler coronary flow velocity and Doppler reserve measurement of distal left anterior descending were recorded at rest and adenosine infusion (140 microgxkg(-1)xmin(-1)) induced hyperemia state, CFR was calculated by the ratio of maximal hyperemia and baseline peak diastolic coronary flow velocity (hCFV and bCFV) before and after atorvastatin treatment.</p><p><b>RESULTS</b>(1) Eight weeks later, total cholesterol and LDL-C levels were significantly lower in statin group than in non-statin group and control group [TC (3.83 +/- 0.80) mmol/L vs. (5.30 +/- 1.18) mmol/L vs. (5.32 +/- 1.17) mmol/L, P < 0.05; LDL-C (2.26 +/- 0.64) mmol/L vs. (3.28 +/- 0.85) mmol/L vs. (3.30 +/- 0.82) mmol/L, P < 0.05]. (2)Baseline CFR levels were significantly lower in statin group and non-statin group than that in control group (2.32 +/- 0.30 vs. 2.25 +/- 0.33 vs. 3.15 +/- 0.34, P < 0.05). Compared with non-statin group and statin group before treatment, 8 weeks statin treatment was associated with reduced bCFV [(26.06 +/- 3.22) cm/s vs. (29.02 +/- 3.36) cm/s and (26.06 +/- 3.22) cm/s vs. (28.43 +/- 3.40) cm/s, P < 0.05], increased hCFV [(77.63 +/- 8.96) cm/s vs. (65.17 +/- 7.22) cm/s and (77.63 +/- 8.96) cm/s vs. (64.58 +/- 6.26) cm/s, P < 0.05] and increased CFR (3.07 +/- 0.29 vs. 2.28 +/- 0.35 and 3.07 +/- 0.29 vs. 2.32 +/- 0.30, P < 0.05). bCFV, hCFV and CFR of statin group post treatment were similar to those of controls (P > 0.05).</p><p><b>CONCLUSION</b>Patients with coronary slow flow were associated with lower CFR which could be significantly improved by statin therapy.</p>

Study on the events of nonfatal drowning among primary and middle school students in a rural town of Guangdong province, 2006 / 中华流行病学杂志

Objective To understand the incidence and characteristics of nonfatal drowning among primary and middle school students in rural area and to provide basic information for intervention.Methods A rural town was selected and all students from 3th-8th grades,10th grade and 11th grade were studied.All data were collected,using a self-administrated questionnaires which was guided by investigator.Results The overall incidence rate of nonfatal drowning was 5.65%(549/9732)and were 7.69%,5.80%,2.39%for primary,secondary and high school students,respectively.Male students had a higher rate(7.14%)than that of females(4.03%).The incidence rates of non-treated,treated in emergency and under hospitalization were 4.52%,0.77% and 0.35%.The major reasons of drowning were swimming (46.88%),falling into waters(15.67%),diving(13.79%)and rescuing others(6.24%).The proportion of drowning occurred in the afternoon,evening,at noon or in the morning were 59.94%,15.64%,14.77%and 9.65%respectively.The common sites of drowning were river/lake(42.48%),swimming pool(19.56%),reservoir(11.39%)and pond(4.38%).66.76%of the drowning cases were witnessed by other person,and 17.86%were conscious when being removed from waters.Conclusion The incidence of nonfatal drowning among students in rural areas was high,and the natural body of waters was the most common site causing drowning while swimming was the major reason of drowning.Intervention targeting on primary and middle sehool students in rural should be carried out to reduce the incidence.

Processing method and HPLC fingerprint of charred radix Scutellariae / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the process and HPLC fingerprint of Charred Radix Scutellariae, and lay a foundation of Charred Radix Scutellariae quanlity control mode.</p><p><b>METHOD</b>Select HPLC-UV fingerprint. Chromatogram condition: Hypersil C18 column (5.0 mm x 200 mm, 5 microm), mixtures of methanol, 0.4% phosphoric acid and acetonitrile as mobile phase in a gradient mode. Flow rate: 1.0 mL x min; Detection wavelength was set at 277 nm.</p><p><b>RESULT</b>There were no evident differences among Charred Radix Scutellariae that were normatively manufactured and processed.</p><p><b>CONCLUSION</b>This test proves the process is feasible, this method recurs well and can be used to provide scieitific basis for the normative process and quanlity control mode of Charred Radix Scutellariae.</p>

Study of HPLC-DAD fingerprint on complex traditional Chinese medicine proprietary preparation-Baoji pills / 中国中药杂志

<p><b>OBJECTIVE</b>Based on 'Back-tracking' method, identification and quality evaluation of complex traditional Chinese medicine (TCM) preparation of Baoji pills (BJP) were carried out by HPLC fingerprint analysis.</p><p><b>METHOD</b>HPLC-DAD fingerprint of BJP was conducted with Zorbax SB-C18 column and non-linear elution with the mobile phase consisted of acetonitrile-0.5% glacial acetic acid at column temperature 30 degrees C and detective wavelengths of 250 nm and 283 nm. From the established chromatographic pattern of BJP, track backward to the corresponding crude herbal drugs in the formula, attribution ofmost peaks in the BJP fingerprint can be disclosed.</p><p><b>RESULT</b>The BJP HPLC fingerprint consisted of 44 peaks among which 35 peaks were assigned by parallel comparison with the fingerprint of the 10 corresponding crude drugs in the formula such as pueraria, pummelo peel, and magnolia bark, etc. and 22 peaks we reidentified by comparison with the chemical reference substances.</p><p><b>CONCLUSION</b>The established HPLC fingerprint represents the whole character of BJP, which enhanced the specialty for control and assessment of the product quality. It exemplified much more effective for quality control than selecting any marker for qualitative or quantitative testing target. And the Back-tracking' experimental method extended the study mentality for complex formula TCM products chromatographic fingerprinting analysis.</p>

HPLC fingerprinting of radix paeoniae alba / 药学学报

To establish a sensitive and specific HPLC method for quality control of Radix Paeoniae Alba, HPLC method was applied for quality assessment of Radix Paeoniae Alba. HPLC analysis was performed on a Symmetry C18 column (250 mm x 4. 6 mm ID, 5 microm, Waters, USA). The mobile phase consisted of acetonitrile (solvent A) and water containing 0.1% (v/v) phosphoric acid (solvent B) at a constant flow rate of 0.8 mL x min(-1). An increasing linear gradient (v/v) of solvent A was used (t/min, % A): (0,10), (5,10), (25,15), (45, 22), (46, 65), (50, 80) and (60, 80). The column temperature was set at 25 degrees C. The chromatograms were monitored at 230 nm and the on-line UV spectra were recorded in the range of 190 - 400 nm. The HPLC chromatographic fingerprinting of Radix Paeoniae Alba, showing 11 characteristic peaks, was established from 28 lots of Radix Paeoniae Alba. The areas of main chromatographic peaks were found to complied with the following rule: paeoniflorin > 1, 2, 3, 4, 6-penta-O-galloyl-glucos > albiflorin > methyl gallate > other compounds. The chromatographic fingerprinting of Radix Paeoniae Alba with high specificity can be used to control its quality and assure lot-to-lot consistency.

The effects of combined beta(1) adrenergic receptor antagonist and beta(2) adrenergic receptor agonist therapy on cardiac function and myocardial apoptosis in heart failure rats / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the effects of combined beta(1) adrenergic receptor (AR) antagonist with beta(2)AR agonist therapy on cardiac function and cardiomyocyte apoptosis in heart failure rats.</p><p><b>METHODS</b>Heart failure was induced by isoproterenol and rats were randomly divided into metoprolol group (50 mg/kg twice daily/gavage, n = 11), combined treatment group (fenoterol 125 microg/kg and metoprolol 50 mg/kg twice daily/gavage, n = 11) and placebo group (saline, n = 10), another normal 9 male Wistar rats served as control group. After 8 weeks' treatment, cardiac function, apoptosis index (AI), Caspase-3 activity, expression levels of bcl-2 and bax protein, organ weight/body weight and collagen volume fraction (CVF) were evaluated.</p><p><b>RESULTS</b>(1) Left ventricular end diastolic dimension, left ventricular end systolic dimension and E/A ratio were significantly increased and fractional shortening, ejection fraction significantly reduced post isoproterenol (all P < 0.05 vs. control) and these changes were significantly attenuated by metoprolol alone (all P < 0.05 vs. placebo) and further attenuated by the metoprolol and fenoterol combination therapy (all P < 0.05 vs. placebo and metoprolol). (2) Left ventricular weight to body weight ratio, lung weight to body weight ratio and CVF were also significantly reduced in metoprolol and combined treatment group than those in placebo group (all P < 0.01). (3) Compared with placebo group, AI and Caspase-3 activity were significantly lower in metoprolol group (all P < 0.01 vs. placebo) and further reduced in combined treatment group (all P < 0.01 vs. metoprolol). (4) The expression level of bax protein was significantly lower in metoprolol group while bcl-2/bax significantly higher than those in placebo group. These changes were more significant in combined treatment group (all P < 0.01 vs. metoprolol).</p><p><b>CONCLUSIONS</b>beta(1)AR antagonist in combination with beta(2)AR agonist further improved the cardiac function and prevented cardiac remodeling compared with using beta(1)AR antagonist alone in heart failure rats. Downregulated bax and upregulated bcl-2/bax expressions might contribute to the observed beneficial therapy effects by reducing cardiomyocyte apoptosis in these animals.</p>

Chronic blocking of beta 3-adrenoceptor ameliorates cardiac function in rat model of heart failure / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Stimulation of the heart beta 3-adrenoceptor (AR) may result in a negative inotropic effect. Being up-regulated, beta 3-AR plays a more important role in the regulation of cardiac function during heart failure. However, the effect of chronic blocking of beta 3-AR on heart failure has not been fully elucidated. In this study, we used a selective beta 3-AR antagonist SR59230A to treat a well defined heart failure rat model chronically, then evaluated its effect on cardiac function and investigated the mechanism.</p><p><b>METHODS</b>Male Wistar rats were chosen randomly as controls (n = 8). Isoproterenol induced heart failure rats were randomly divided into ISO group (n = 10) and SR group (n = 10). The ISO group received intraperitoneal injection of 1 ml saline twice a day; the SR group received intraperitoneal injection of SR59230A 85 nmol in 1 ml saline twice a day; and the control group received no treatment. The treatment was started 24 hours after the last isoproterenol injection and continued for 7 weeks. Then we measured the following indexes: the ratio of heart weight to body weight (HW/BW) and the ratio of left ventricular weight to body weight (LVW/BW), collagen volume fraction (CVF), left ventricular end diastolic dimension (LVEDd), left ventricular end systolic dimension (LVESd), ejection fraction (EF), fractional shortening (FS) and the ratio of E wave to A wave (E/A), the mRNA and protein expression of beta 3-AR and eNOS, and cGMP level in the heart.</p><p><b>RESULTS</b>The ratios HW/BW and LVW/BW were significantly increased in the ISO group compared with the control group (P < 0.01), but they were limited in the SR group (P < 0.05 compared with the ISO group). CVF increased in the ISO group and the SR group (P < 0.01), but it was significantly attenuated in the SR group (P < 0.01). LVEDd, LVESd and E/A ratio were significantly increased in the ISO group compared with the control group (P < 0.01), while EF and FS were significantly decreased (P < 0.01). Compared with the ISO group, the SR group showed that LVEDd, LVESd and E/A ratio were significantly decreased (P < 0.01), whereas EF and FS were significantly increased (P < 0.01). beta(3)-AR and eNOS mRNA and protein in the ISO group were significantly increased when compared with the control group (P < 0.01). These increases were all attenuated in the SR group compared with the ISO group (P < 0.01). The level of cGMP in myocardial tissue was significantly increased in the ISO group compared with the control group (P < 0.01), whereas SR59230A treatment normalized this increment (P < 0.01).</p><p><b>CONCLUSIONS</b>Chronic blocking of beta 3-AR could ameliorate cardiac function in heart failure rats and its mechanism involves inhibition of the negative inotropic effect and attenuation of cardiac remodeling.</p>

Analysis of hydrochloride 4-methyl-piperazine-1-carbodithioc acid 3-cyano-3,3-diphenyl-propyl ester and its metabolites in rats by HPLC-ESI/ITMSn / 药学学报

<p><b>AIM</b>To identify the main metabolites of hydrochloride 4-methyl-piperazine-1-carbodithioc acid 3-cyano-3,3-diphenyl-propyl ester (TM208) in rats.</p><p><b>METHODS</b>Rat feces, urine and plasma samples were collected after ig 500 mg x kg(-1) TM208, then the samples were extracted and concentrated using ethyl acetate. The treated samples were analyzed by HPLC-ESI/ITMSn. The structures of metabolites were elucidated according to the rules of drug metabolism and disposition in vivo and the characteristic fragmentation behaviors of TM208 in ESI-ITMSn.</p><p><b>RESULTS</b>Eight phase I metabolites were identified existing in rat feces, five of them were also found in rat urine and plasma, but no phase II metabolite was found.</p><p><b>CONCLUSION</b>The HPLC-ESI/ITMSn method is rapid, highly sensitive and specific and it is suitable for the identification of TM208 and its metabolites in rats.</p>

Antigen-specific tolerance induced by IL-10 gene modified immature dendritic cells in experimental autoimmune myocarditis in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Experimental autoimmune myocarditis (EAM) in rats is a T-cell-mediated disorder. The initiation and maintenance of autoimmune responses in EAM depend on the maturation state of dendritic cells. IL-10 is a pleiotrophic immunomodulatory cytokine that functions at different levels of the immune response, so it has emerged as a promising therapeutic factor for the treatment of autoimmune/inflammatory diseases. This study was designed to test the hypothesis that IL-10 gene modified bone marrow-derived immature dendritic cells (iDCs) ameliorate EAM and to explore the underlying mechanisms.</p><p><b>METHODS</b>EAM was induced using the methods of cardiac myosin immunization on day 0 and day 7. Immature and mature bone marrow-derived dendritic cells (BMDCs) were generated without or with the stimulation by lipopolysaccharide (LPS) and the phenotype was analyzed by flow cytometry. Some of the iDCs were transfected by pcDNA3-IL-10 plasmid. 2 x 10(6)/per rat mature DC (mDC), immature DC (iDC), pcDNA3 transfected iDC, pcDNA3-IL-10 transfected iDC or phosphate buffered saline (PBS) were injected intravenously for treatment 5 days after the first immunization. On day 21, HE staining was performed to detect the myocardial inflammation and T lymphocyte proliferation assay was used to determine the effects of IL-10 gene transfected iDC on autoreactive T cell proliferation. Expression of IkappaB, the inhibitor of NF-kappaB pathway, was determined by Western blot.</p><p><b>RESULTS</b>BMDCs generated in a medium supplemented with granulocyte-macrophage-colony-stimulating factor (GM-CSF) were relatively immature, as determined by flow cytometry. However, stimulation with LPS induced these cells to become mature (m) DCs with higher levels of surface major histocompatibility complex (MHC)-II and costimulatory molecules. Intravenous administration of iDCs, especially pcDNA3-IL-10 transfected iDC, ameliorated the histopathological severity of the myosin induced-EAM, and the effect was lost after the DCs underwent maturation induced by in vitro exposure to LPS. IL-10 gene modified iDC inhibited the antigen specific T cell responses towards cardiac myosin. IkappaB protein was up-regulated significantly in the IL-10 gene modified iDC group.</p><p><b>CONCLUSIONS</b>IL-10 gene modified iDC induced antigen-specific tolerance in EAM. The underlying mechanisms may be related to costimulatory molecules down-regulation and NF-kappaB pathway inhibition.</p>

IL-10 gene modification on immature dendritic cells induces antigen-specific tolerance in experimental autoimmune myocarditis / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate whether IL-10 gene modification on immature dendritic cells (iDC) could induce autoimmune tolerance in rat experimental autoimmune myocarditis (EAM).</p><p><b>METHODS</b>EAM was induced by cardiac myosin immunization on day 0 and day 7 in rats. A total of 2 x 10(6) mature DC (mDC), iDC, pcDNA3 transfected iDC, pcDNA3-IL-10 transfected iDC or PBS were injected intravenously at 5th immunization day. Three weeks later, echocardiography and HE staining were performed to observe the cardiac function and myocardial inflammation. Th1/Th2 cytokines were detected by ELISA and MHC-II molecules, costimulatory molecules were identified by flow cytometry. In vitro T lymphocyte proliferation assay and adoptive transfer of DCs were performed to determine the antigen specific tolerance induced by IL-10 gene modification on iDCs.</p><p><b>RESULTS</b>EAM rats treated with pcDNA3-IL-10 transfected iDC showed improved cardiac function and reduced inflammatory cells infiltration into myocardium. Moreover, lower Th1 and higher Th2-type response was induced, MHC-II and costimulatory molecules down-regulated and antigen specific immunological responses towards cardiac myosin inhibited in pcDNA3-IL-10-iDC treated EAM rats.</p><p><b>CONCLUSION</b>Treatment with IL-10 gene modified iDCs could ameliorates EAM by inducing Th2 polarization and down-regulation of MHC-II molecules and costimulatory molecule expressions.</p>

The epidemiological study on human immunodeficiency virus infection among paid blood donors living in Shandong provincial China Comprehensive Response Project Areas / 中华流行病学杂志

<p><b>OBJECTIVE</b>To understand the current epidemic situation and high risk factors of human immunodeficiency virus (HIV) infection among paid blood donors living in Shandong provincial China Comprehensive Response (CARES) Project Areas.</p><p><b>METHODS</b>All residents between 20 to 60 years old were selected from one or several counties in August 2003.</p><p><b>RESULTS</b>There were 19 HIV(+) infections among 661 subjects interviewed. HIV prevalence rate among paid blood donors was higher (3.98%) than that of others (0.48%) while HIV prevalence rate was higher in plasma donors (7.24%) than that in both plasma and full blood donors (2.90%). There was no infections identified in full blood donors. Donors who donated blood during 1994 - 1995 had a higher prevalence rate (7.07%) than those who started donation after 1995 and those began donation before 1993 (0.99%). The rate of condom use was lower among paid blood donors (13.72%) than that of others. There was a lower rate of voluntary HIV testing among paid blood donors than that of others.</p><p><b>CONCLUSION</b>The main high risk population of HIV infection were paid donors in CARES Project Areas, whose risk factor was plasma donation and were infected mainly before 1995. Both the rate of condom use and HIV testing were all very low, indicating that they knew little on HIV/AIDS and paid less attention to self-proctection. It is necessary to enhance HIV/AIDS health education and behavior intervention on paid blood donors.</p>

The experimental study on changes of endothelial nitric oxide synthase and plasminogen activator inhibitor-1 protein in the canine atrial fibrillation model / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the changes in the expressions of endothelial nitric oxide synthase (eNOS) and plasminogen activator inhibitor-1 (PAI-1) and the alterations of nitric oxide (NO) concentration in atrial endocardium in atrial fibrillation (AF) in order to investigate the mechanisms that contribute to thrombosis.</p><p><b>METHODS</b>In canine AF was produced with rapid atrial pacing at 400 bpm for 6 weeks, whereas the controls had no atrial pacing. NO production was measured by NO-specific microelectrode. The expression of endocardial eNOS and PAI-1 protein were determined by Western blot analysis and immunohistochemical Staining. Plasma levels of PAI-1 were analysed by Enzyme-linked immunoadsorbent assay.</p><p><b>RESULTS</b>Left atrial NO concentration was decreased in AF than that in controls [(23.4 +/- 5.8)nmol/L vs (63.8 +/- 16.1)nmol/L, P < 0.01]. Endocardial eNOS expression was also significantly decreased (855 +/- 217 vs 2320 +/- 694, P < 0.05), whereas the expression of the PAI-1 was increased (3164 +/- 827 vs 1371 +/- 352, P < 0.01). Neither NO concentration, nor PAI-1, eNOS expression were altered in the right atria at the same time. A significant increase for plasma levels of PAI-1 was also detected in AF group. No correlation was found between eNOS and PAI-1 protein expression (r = 0.217, P > 0.05).</p><p><b>CONCLUSION</b>In the canine model AF was associated with a marked decrease in endocardial NOS expression and NO concentration and with an increase in PAI-1 expression in the left atrium, which may contribute to the thrombosis in AF.</p>