Infective endocarditis(IE) is a kind of endocardial infection which cardiac intima is affected by some pathogens.Intravascular catheter,implantable artificial device and surgery are the common reasons for IE,congenital heart diseases and cardiac surgery are the main causes for IE in children.The incidence of infective endocarditis is high and case fatality rate is as high as 20％.The dominant pathogen of IE is gram-positive bacteria.Modified Duke standard is the gold standard in the diagnosis of IE,some other imaging evidence and new laboratory tests and biomarkers for diagnosis of IE have improved the sensitivity of the diagnostic criteria.Good oral hygiene and regular dental check are the most effective prevention measures.The idea ofendocarditis management team in the newest guidelines on IE requires muhidisciplinary experts to participate in diagnosis and treatment of IE.Individualized treatment is the best way to improve the patients survival rate.

With the inappropriate use of antibiotics, the situation of bacterial resistance is more and more severe. The emergence of multidrug-resistant (MDR) bacteria has made it difficult to cure the infections in clinical. For treatment the infections caused by MDR and reducucton of the generation of resistant bacteria, researchers are actively studying on the non-antibiotic substances for antibacterial activity. In this paper, the advances in those with conifrmed effects such as phage therapy, metal/chelation therapy, immunization therapy, photodynamic therapy, and nitric oxide (NO)-based therapies, small molecule inhibitors, antimicrobial peptides and Chinese herb were reviewed.

Objective To investigate pediatric infective endocarditis(IE) risk factors and the feature of pathogen.Methods We conducted a retrospective study of 46 cases who were diagnosed as IE from January 2000 to June 2007.Sixteen variables such as sex,primary disease,infectious site,complication,culture result and therapeutic measure were selected for logistic regression analysis.Results Forty-six IE patients accounted for 0.78‰ of all the hospitalized patients during the same period.Of 46 cases,40 had heart diseases.The incidence rate of left-sided endocarditis was higher than that of right-sided endocarditis.Twenty-four had positive blood culture result,one patient had positive culture from vegetation sample.The total positive culture rate was 54%.Gram-positive bacteria were found in 15 cases,and the most common organisms were α-hemolytic streptococcus.Gram-negative bacteria were in 7 cases and fungus infection was present in 3 cases.After antiboitic treatment,40 were cured,6 died.In the logistic regression model,the variables significantly associated with death included negative blood culture (OR=25.127,95%CI=1.110-363.236),hematological system disease (OR=28.620,95%CI=2.261-354.448) and multiple organ failure (OR=19.843,95%CI=0.786-221.754).Conclusion Streptococcus viridans is the most common pathogen in pediatric IE in our hospital.Higher incidence in the left heart than that in the right heart is found.Negative blood culture,hematological system disease and MOF are the risk factors in IE patients.

OBJECTIVE:To establish the method for pharmacokinetic study of luteolin and cynaroside in rats and to determine pharmacokinetic parameters. METHODS:16 SD rats were randomly divided into luteolin group (sublingual iv,1.34 mg/kg) and cynaroside group(sublingual iv,0.64 mg/kg). 0.5 ml blood were collected before administration and 0,15,30 min and 1,2,3,4,6, 8,12,24,48 h after administration respectively to prepare plasma. UPLC-TQ-MS was adopted to determine plasma concentration, and pharmacokinetic parameters were calculated. A CORTECSTM UPLC? C18(100 mm×2.1 mm,1.6 μm)column was used with mobile phase consisted of acetonitrile-water (containing 0.1% formic acid) at a flow rate of 0.4 ml/min,the column temperature was set at 40 ℃,and quercetin was used as internal standard. RESULTS:The linear range of luteolin and cynaroside were 2.5-500 ng/ml (r=0.998 2) and 10-2 500 ng/ml (r=0.993 5). The lowest quantitation limits were 1 and 2.5 ng/ml,and extraction were 70.75%-87.72% and 75.40%-91.18%(n=6);RSD of inter-day and intra-day were all lower than 10%(n=3). Pharmacokinetic parameters as t1/2 were (1.88 ± 0.32) and (1.57 ± 0.08) h;CL were (0.77 ± 0.18) and (0.06 ± 0.01) L/(h·kg);AUC0-6 h were (189.60±40.04)and(1 093.14±187.36)ng·h/ml;AUC0-∞ were(195.18±38.37)and(1 097.11±188.07)ng·h/ml. CONCLU-SIONS:The method can be used for pharmacokinetic study of luteolin and cynaroside in rats,and the pharmacokinetics of them in rats are in line with two-compartment model.

Objective:To establish an ultra performance liquid chromatography-tandem quadrupole mass spectrometry method for the determination of warfarin and its metabolite 7-hydroxywarfarin in human plasma. Methods: An ACQUITY UPLC? BEH C18 (50 mm × 2. 1 mm, 1. 7 μm) column was used as the stationary phase at 40℃. The mobile phase consisted of acetonitrile and water (con-taining 0. 1% formic acid) with gradient elution at a flow rate of 0. 4 ml·min-1 . Warfarin-d5 was used as the internal standard. The analytes were detected on a triple-quadrupole mass spectrometer equipped with an ESI interface in a positive mode. Results:The reten-tion time of warfarin and 7-hydroxywarfarin was 1. 8 min and 1. 5 min, respectively. Excellent linear calibration curve of warfarin and 7-hydroxywarfarin was obtained within the concentration range of 25-2 000 ng · ml-1 ( r =0. 999 3 ) and 5-500 ng · ml-1 ( r =0. 999 6), respectively. The lower limit of quantification of warfarin and 7-hydroxywarfarin was 5 ng·ml-1 and 2. 5 ng·ml-1 with the average recovery of 96. 9%-105. 3% and 97. 1% -103. 3%, respectively. The intra-and inter-day standard deviations were both less than 10%. Conclusion: The method is accurate and simple, and suitable for the determination of warfarin and its metabolite 7-hydroxywarfarin in human plasma.

Objective:To investigate the correlation between hematopoietic cell kinase (HCK) and the expression level of the mitochondrial ribosomal protein L13 (MRPL13) and hematopoietic multimode ultrasound.Methods:204 female breast cancer patients treated by surgery in Quzhou people’s Hospital from Jan. 2017 to Sep. 2020 were selected as study subjects. Breast cancer tissues and adjacent normal tissues were extracted intraoperatively. Preoperative conventional ultrasound, shear wave elastography (SWE) and contrast-enhanced Ultrasonography (CEUS) were used to detect HCK and MRPL13 expression levels. Univariate analysis and binary Logistic regression were used to analyze the correlation between multi-mode ultrasonic features and HCK and MRPL13.Results:The positive expression ratios of HCK and MRPL 13 in breast cancer tissues were significantly higher than those in adjacent tissues ( χ2 was 5.625, 7.197; P was 0.018, 0.007) . In conventional ultrasound features, the proportions of HCK-positive breast cancer patients with irregular mass edges, microcalcifications, and grade II to III blood flow classification were significantly higher than those of HCK-negative patients ( χ2 was 7.437, 16.684, 23.262; P was 0.006, <0.001, <0.001) ; The proportion of MRPL13-positive breast cancer patients with a maximum diameter of ≥2 cm, irregular edges of the tumor, and grade II-III blood flow classification was significantly higher than that of MRPL13-negative patients ( χ2 was 4.676, 11.118, 8.389; P was 0.031, 0.001, 0.004) . For SWE signs, the proportion of HCK positive breast cancer patients with hard ring sign was significantly higher than that of HCK negative patients ( χ2=11.220, P=0.001) ; the proportion of MRPL13 positive breast cancer patients with hard ring sign and black hole sign was significantly higher than that of MRPL13. Those who were negative ( χ2 was 4.482, 8.775; P was 0.034, 0.003) . Among CEUS characteristics, the proportion of HCK-positive patients with high enhancement was significantly higher than that of HCK-negative patients ( χ2=7.356, P=0.007) ; the proportion of MRPL13-positive patients with high enhancement and late regression was significantly higher than that of MRPL13-negative patients ( χ2 was 9.165, 7.631; P was 0.002, 0.006) . The results of binary logistic analysis showed that there was microcalcification ( OR=4.619, 95% CI=2.657-8.119, P=0.009) , blood flow classification II to III ( OR=4.150, 95% CI=2.547-7.954, P=0.015) and high enhancement of CEUS ( OR=4.150, 95% CI=2.547-7.954, P=0.015) are independent risk factors for positive expression of HCK; blood flow grade II to grade III ( OR=4.213, 95% CI=3.145-8.557, P=0.012) , appearance of black hole sign ( OR=5.246, 95% CI=2.864-10.378, P<0.001) and high enhancement of CEUS ( OR=3.872, 95% CI=1.887~6.438, P=0.026) were the independent risk factors for the positive expression of MRPL13. Conclusion:The multimodal ultrasonographic features of breast cancer are helpful to predict the expression levels of HCK and MRPL13, so as to provide new imaging ideas for early diagnosis of breast cancer, the designation of treatment options and the preoperative non-invasive assessment of breast cancer prognosis.

Objective To investigate the pathogen of 21 infective endocarditis (IE) cases treated with operation in Shanghai Children's Medical Center from 2007 to 2010.Methods Blood culture,vegetation culture and vegetation PCR assay(target gene to the conserved region V3 in 16SrRNA gene) were detected in 21 IE patients; multiplex PCR amplification of staphylococci for methicillin-resistant staphylococcus was performed.Results Of 21 IE cases,20 cases were detected positive by vegetation PCR with the detection rate of 95.2％,12 IE cases were detected positive by blood culture with the detection rate of 57.1％,2 IE cases were detected positive by vegetation culture with the detection rate of 9.5％.The difference of the positive rates of the three methods was statistically significant (P ＜ 0.0001).The vegetation PCR of one case was actinobacillus actinomycetemcomitans,while the blood culture was haemolysis pasteurell which was inconsistent with the vegetation PCR result.Howerver,the PCR result of colony obtained by blood culture was consistent with vegetation PCR that was confirmed as actinobacillus actinomycetemcomitans.The endocardium PCR results of 11 IE cases were consistent with the results of blood culture.MecA gene was detected by multiplex PCR,which could identify methicillin-resistant staphylococcus quickly,sensitively and accurately and could also effectively identify methicillin resistant staphylococcus aureus,when coupled with femA gene detection,thus glycopeptides antibiotic could be prescribed promptly.All the 21 patients recovered and discharged without infection recurrence in the follow-up.Conclusion Universal primer V3 coupled with multiplex PCR can improve vegetation pathogen detection rate of IE patients and is minimally influenced by antibiotic therapy.Multiplex PCR can be applied for etiological diagnosis of IE patients with indication of surgery and negative blood culture or difficult diagnosis,contributing to post-surgery antibiotics selection and improvement of recovery rate of IE patients.

Objective To study the clinical characteristics, treatment and prognosis of infective endocarditis in children. Methords Clinical data from 83 patients of infective endocarditis admitted from 1998 to 2012 were retrospectively analyzed. Results In a total of 83 patients, there were 53 males and 30 females, and the average age was 6.8±4.6 years. The main clinical characteristics were fever (77.1%) and mild to moderate anemia (71.1%). The C-reaction protein (67.5%), erythrocyte sedimen-tation rate (60.2%), and white blood cell (47.0%) were elevated. Twenty (24.1%) patients had embolism. Blood culture was pos-itive in 56 (67.5%) cases with bacteria mainly being Gram-positive and Streptococcus and Staphylococcus accounted for 89.3%. Vancomycin and other sensitive antibiotics were effective. Neoplasm was detected in 68 cases (82%) by transthoracic echocar-diograerphy. Fifty-ifve (66.2%) patients underwent cardio surgery. Seven patients (8.4%) died. Conclusion In recent years, the distribution of pathogenic bacteria in infective endocarditis had changed. Streptococcus mitis and Staphylococcus aureus has become a major pathogens and need to be treated by vancomycin and other sensitive antibiotics. The detection rate of neoplasm is higher by echocardiography.

Objective To explore the influence on the bad eating habits of diabetes by the management of diabetes education with families participation.Method Sixty-six patients with type 2 diabete mellitus were chosen as study object.They were divided into the experiment group and the control group at random.The diabetic knowledge and die behavior education were taken to the two groups and the families of the experiment group.The bad eating habits of the two groups were investigated before and after management. Results The snack,night snack and out eating times were significantly decreased in the experiment group than the control group and before management.There were statistical significant difference(all P<0.05).Conclusion The management of diabetes education with families participation can improve the bad eating habits so as to delay the progression of diabetes.

Objective:To establish an ultra performance liquid chromatography-tandem quadruple mass spectrometry ( UPLC-MS/MS) method to determine CYP2C9 activity in vitro. Methods:An ACQUITY UPLC? BEH C18 (100 mm × 2. 1 mm, 1. 7 μm) column was used as the stationary phase at 30℃. The mobile phase consisted of acetonitrile-water ( containing 0. 1% formic acid and 0. 5%ammonia water) (40∶60, v/v). The flow rate was 0. 2 ml·min-1. Chlorpropamide was used as the internal standard. The MS condi-tions were as follows:ESI with positive ion detection mode. Self-prepared CYP2C9?1, ?2, ?3 and ?13 protein were incubated with tolbutamide at 37℃ and 800μl ethyl acetate was added to stop the reaction. After centrifuged at 10 000g, the organic layer was then dried using nitrogen, the residue was re-dissolved in 200μl mobile phase and determined by UPLC-MS/MS. Results: The reten-tion time of 4-hydroxytolbutamide was 1. 21 min. An excellent linear calibration curve of 4-hydroxytolbutamide was obtained within the concentration range of 0. 05-5 ng·μl-1(r=0. 999 8). The lower limit of quantification of 4-hydroxytolbutamide was 0. 01 ng·μl-1 with the average recovery of 99. 3%-100. 3%. The intra- and inter-day RSDs were all less than 5%. There was no interference from the endogenous substances existing in the incubation system. The catalytic activity of the variants CYP2C9?2,?3 and?13 after tol-butamide was incubated with CYP2C9?1,?2,?3 and?13 was 47. 3%, 11% and 0. 3% of wild type CYP2C9?1. Conclusion:The method is simple and stable, and suitable for the fast evaluation of cytochrome CYP2C9 activity in vitro and relevant studies on the inhibitors.