Application and Exploration of Big Data Mining in Clinical Medicine / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To review theories and technologies of big data mining and their application in clinical medicine.</p><p><b>DATA SOURCES</b>Literatures published in English or Chinese regarding theories and technologies of big data mining and the concrete applications of data mining technology in clinical medicine were obtained from PubMed and Chinese Hospital Knowledge Database from 1975 to 2015.</p><p><b>STUDY SELECTION</b>Original articles regarding big data mining theory/technology and big data mining's application in the medical field were selected.</p><p><b>RESULTS</b>This review characterized the basic theories and technologies of big data mining including fuzzy theory, rough set theory, cloud theory, Dempster-Shafer theory, artificial neural network, genetic algorithm, inductive learning theory, Bayesian network, decision tree, pattern recognition, high-performance computing, and statistical analysis. The application of big data mining in clinical medicine was analyzed in the fields of disease risk assessment, clinical decision support, prediction of disease development, guidance of rational use of drugs, medical management, and evidence-based medicine.</p><p><b>CONCLUSION</b>Big data mining has the potential to play an important role in clinical medicine.</p>

Establishment of human cardiac C protein induced experimental autoimmune myocarditis model in rat / 中华心血管病杂志

<p><b>OBJECTIVE</b>To construct the recombinant plasmid of human cardiac C protein (CCP) peptide with immunogenicity and to express, purification and renature fusion protein. The fusion protein was injected to Lewis rats to establish experimental autoimmune myocarditis (EAM) model.</p><p><b>METHODS</b>Total RNA was extracted from human heart and used as the template for reverse transcriptase-directed cDNA synthesis. The cDNA was then amplified by polymerase chain reaction (PCR) using oligonucleotide primers specific for CCP peptide with immunogenicity. Subsequently, the purified CCP peptide gene was cloned into PEASY-T1 vector and the ligated product was identified by PCR and DNA sequence analysis. Then the CCP target gene of positive clone was inserted into the pQE30, a prokaryotic expression vector, and the inserting plasmid was transformed into Escherichia coli. host M15. The positive clone extracted from the bacterium liquid was sieved by insertional inactivation sieve method and identified by PCR of bacterium liquid, CCP immunological peptide was purified and renatured in semipermeable membrane. EAM model in Lewis rats was induced by injection of mixture of 100 µg CCP fusion protein immunological peptide and 2.5 g/L completed Freund adjuvant from two double foot pad and subsequent abdominal injection of 0.5 µg pertussis toxin. Two, four, six, and eight weeks after immunization, hemodynamic evaluation was made and hearts underwent histological examination.</p><p><b>RESULTS</b>The DNA sequence analysis for cloning vector extraction revealed that the CCP target gene was cloned into pQE30 exactly. The DNA of 1000 bp length was obtained by PCR examination of bacterium liquid with transformation of express recombinants which were consistent with the expected size. Purified fusion protein in vertical slab gel electrophoresis showed 35 000 as expected. The recombinant CCP fusion protein existed in inclusion bodies of E. coli and amounted to 80% - 90% of the total protein. Hemodynamic and histological evaluations showed typical acute inflammatory responses at 2 weeks, subacute inflammatory and fibrosis changes at 4 weeks after injection, and signs of chronic dilated cardiomyopathy at 6 weeks post injection.</p><p><b>CONCLUSION</b>Combination of gene clone technique and histidine tag protein purification technique can be used to synthesize human cardiac C protein to induce EAM model in Lewis rat.</p>

Experimental study of MMP-2 inhibitor treatment of experimental autoimmune myocarditis in Lewis rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the inhibitor of matrix metalloproteinase-2 (MMP-2) (2R)-2-[5-[4-[ ethyl-methylamino] phenyl [thiophene-2-sulfonylamino]-3-methylbutyric acid (TISAM) therapeutic effect on experimental autoimmune myocarditis (EAM) in Lewis rats.</p><p><b>METHODS</b>Treatment protocol of oral administration of 5 mg/kg TISAM once a day for 14 days was performed on EAM Lewis rats. EAM Lewis rats were divided into 3 groups: treatment in early, middle and later stage respectively (n = 20). After experiment at the designate time point, the rats were euthanatized and hearts were harvested. Cardiac inflammatory score, fibrosis score and content, and infiltration of macrophages and T lyminflammatory score, fibrosis score and content, and infiltration of macrophages and T lymphocytes, message RNA (mRNA) expression of matrix metalloproteinase (MMP)-2 and MMP-9 and protein activity of gelatinase were determined.</p><p><b>RESULTS</b>TISAM treatment in early phase was invalid (treatment started from the creation of the model), treatment in middle and later phase was effective (treatment started from 7 and 14 day after the creation of the model).</p><p><b>CONCLUSION</b>Inhibitor of MMP-2 can block ventricular remodeling in middle stage in EAM Lewis rats. The mechanism maybe alleviate the inflammatory cell cardiac infiltration, decrease the mRNA expression of MMP-2 at transcript level and downregulate gelatinase activity at protein level.</p>

Effects of matrix metalloproteinase-9 inhibitor in Lewis rats with experimental autoimmune myocarditis / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of matrix metalloproteinase-9 (MMP-9) inhibitor minocyclin hydrochloride in Lewis rats with experimental autoimmune myocarditis (EAM).</p><p><b>METHODS</b>EAM was induced by injection of cardiac C protein emulsified in completed Freund adjuvant in double footpad and intraperitoneal injection of pertussis toxin on 6- to 8-week old Lewis rats. Sixty EAM Lewis rats were divided into 3 groups (early, middle and late intervention groups, n = 20 each: 10 minocyclin treated and 10 control rats). In early intervention group, rats in treatment group received intraperitoneal injection of minocyclin hydrochloride from 1(st) to 21(st) day after immunization; in middle intervention group, rats were treated from 8(th) to 28(th) day after immunization and in late intervention group, rats were treated from 15(th) to 35(th) day after immunization (50 mg/kg body weight, once daily). Control rats received intraperitoneal injection of same volumetric physiological saline at corresponding time periods. At the end of intervention, rats were euthanatized and hearts were harvested. Paraffin sections were used for hematoxylin and eosin stain to determine the inflammatory score, for picrosirius stain to determine fibrosis score and collagen content, and for immunohistological stain to determine macrophages and T lymphocytes. Real time PCR was used to detect mRNA expression of myocardial MMP-2 and MMP-9. Cryostat sections were used for in situ zymography to detect protein activity of gelatinase.</p><p><b>RESULTS</b>Inflammatory score in cardiac paraffin slides, number of cardiac macrophages and T lymphocytes, cardiac interstitial fibrosis score and content, expression of MMP-2, 9 mRNA and activity of gelatinase in treatment group were all significantly lower than in control group for early and middle intervention groups (inflammatory score: early control group vs. treatment group: 3.03 ± 1.35 vs.1.51 ± 0.36, P < 0.05, middle control group vs. treatment group: 3.75 ± 0.29 vs. 2.11 ± 0.82, P < 0.01; cardiac interstitial fibrosis score, early control group vs. treatment group: 2.75 ± 0.29 vs.1.51 ± 0.35, P < 0.01, middle control group vs. treatment group: 2.50 ± 0.41 vs. 1.61 ± 0.42, P < 0.05; gelatinase, early control group vs. treatment group: 162 367 ± 5095 vs. 62 366 ± 2131, P < 0.01, middle control group vs. treatment group: 184 256 ± 5427 vs. 113 197 ± 4809, P < 0.01) while these parameters were similar between minocyclin-treated and control rats in late intervention group (all P > 0.05).</p><p><b>CONCLUSIONS</b>MMP-9 plays an important role in the pathogenesis of autoimmune myocarditis. Inhibition of MMP-9 in early and middle stage could significantly attenuate inflammatory responses and myocardial fibrosis in this experimental EAM model.</p>

Transfection of Nitric Oxide Synthase Gene with Adenovirus Can Inhibit the Intimal Hyperplasia of Venous Autografts / 中国康复理论与实践

@#ObjectiveTo investigate the effects of nitric oxide synthase (NOS) genetic transfection on the intimal hyperplasia of venous autografts. MethodsThe external jugular veins were autografted into abdominal aorta arteries in 20 Wistar rats, which were divided evenly into experimental or control groups. The transplanted veins of experimental group were immersed in the adenovirus-mediated eNOS gene solution for 15 minutes just before anastomosis. The transplanted vascular samples were taken out 2 weeks after operation. The intimal thickness(IH), degree of restenosis(DR), expression of PCNA and NOS mRNA were determined with histology and transcription polymerase chain reaction (PCR). ResultsThe IH, DR and PCNA decreased, while the expression of eNOS mRNA increased comparing with control group(P<0.01). ConclusionTransfection of NOS gene can inhibit the intimal hyperplasia of venous autografts.