Adrenomedullin ; metabolism ; Child ; Endothelin-1 ; metabolism ; Female ; Heart Defects, Congenital ; complications ; Humans ; Hypertension ; metabolism ; Hypertension, Pulmonary ; metabolism ; Male ; Nitric Oxide ; metabolism

Objective To discuss the clinical value of 99Tcm-sestamibi(99Tcm-MIBI) myocardial perfusion imaging on detecting myocardial ischemia in children with Kawasaki disease(KD) at convalescence period.Methods Twenty-one children wih KD at convalescence period were divided into 2 groups according to results of echocardiography.Four cases with coronary artery dilation,17 cases without coronary artery dilation.All cases accepted dipyridamole stress myocardial perfusion imaging.These patients who had positive results were given rest myocardial perfusion imaging again next day.Results Among 21 cases,9 cases(42.8%) were positive in perfusion imaging.Four cases with coronary artery dilation showed myocardial ischemia in different degree detected by myocardial perfusion imaging.Among 17 cases without coronary artery dilation,5 cases(29.4%) were positive.Conclusions Compared to echocardiography,99Tcm-MIBI myocardial perfusion imaging can objectively evaluate the location,extent and degree of myocardial ischemia of children with KD.It will be a routine test in observing its phase development.

Objective To explore the changes of plasma angiotensinⅡ (AngⅡ) and cardiac function,and the curative effect of children with acute viral myocarditis (VMC) treated with captopril(CAP).Methods Concentrations of plasma AngⅡ were measured with radio-immunity and cardiac function was detected by Doppler echocardiography for the VMC group (n=60) before and after treatment [the CAP group (n=30), the routine group (n=30) and the control group (n=30)].Results 1. The level of plasma AngⅡ significantly increased and the contractive and diastolic function obviously declined in children with acute VMC. There was a significant difference between VMC group and control group, with a significant correlation between the level of AngⅡand the contractive diastolic function.2. Compared with the level before treatment, the level of AngⅡ decreased and the contractive function obviously ameliorated in two groups; the diastolic function obviously ameliorated in the CAP group and did not ameliorate in the routine group after treatment. In CAP group the level of AngⅡ and the cardiac function significantly improved; there were statistical differences between the two groups after treatment.Conclusions 1.The increase of the plasma AngⅡ was an important factor for decrements of the contractive and diastolic function in acute viral myocarditis.2.It could decrease the concentration of plasma AngⅡ and ameliorate cardiac function in children with acute VMC treated with captopril,which was an effective therapy for acute VMC.

OBJECTIVETo investigate the distribution of babA2 cagA and vacA genotypes of Helicobacter pylori (Hp) in chronic gastritis and peptic ulcer and to discuss the relationship between babA2, cagA and vacA genotypes of Hp and chronic gastritis and peptic ulcer.

METHODSbabA2, cagA genotypes and vacA subtype of 58 Hp strains isolated from patients of Zhejiang province with chronic gastritis or peptic ulcer were tested by polymerase chain reaction.

RESULTSThe positive rates of babA2, cagA, vacAs1a, vacA m1 and vacA m2 of 58 Hp strains were 87.9%, 100%, 93.1%, 1.7% and 65.5%, respectively. There were no significant differences between the positive rates of babA2, vacA s1a and vacA m2 genes of Hp strains isolated from patients with chronic gastritis and peptic ulcer.

CONCLUSIONThe genotypes of Hp isolated from patients of Zhejiang province were predominatly babA2 positive, cagA positive and vacA s1a/m2. The relationships between babA2, cagA and vacA genotypes of Hp and chronic gastritis and peptic ulcer can not be identified.

Adhesins, Bacterial ; Antigens, Bacterial ; Bacterial Proteins ; genetics ; Carrier Proteins ; genetics ; Chronic Disease ; Gastritis ; microbiology ; Genotype ; Helicobacter pylori ; genetics ; Humans ; Peptic Ulcer ; microbiology

AIM:To investigate the protective effect of basic fibroblast growth factor(bFGF)on the heart of mice with myocardial infarction and its mechanism.METHODS:The model of myocardial infarction was established by the ligation of left anterior descending artery of C57/B6 mice(8～12 weeks old)after lateral thoracotomy.The mice were divided into sham operation group ,myocardial infarction group and bFGF administration group.bFGF at 0.5μg was intra-peritoneally injected on alternate days after myocardial infarction for 7 d.Cardiac Doppler ultrasonography was used to de-tect cardiac function after myocardial infarction for 28 d,and left ventricular end-diastolic diameter ,left ventricular end-systolic diameter,left ventricular ejection fraction and left ventricular shortening fraction(LVFS)were used to evaluate cardiac function.After myocardial infarction for 28 d,the mice were sacrificed and the hearts were collected for preparing pathological sections.The degrees of myocardial fibrosis and angiogenesis in the myocardial infarction area were observed. Western blot was used to detect the indicators of angiogenesis.RESULTS:The results of Masson staining showed that bF-GF administration significantly reduced myocardial fibrosis at 28 d after myocardial infarction.Cardiac ultrasound data showed that cardiac functions in myocardial infarction group were poorer than those in sham group ,and bFGF administration significantly improved cardiac functions.Immunofluorescence staining showed that neovascularization in myocardial infarc -tion area of bFGF administration group was more than that in myocardial infarction group.The results of Western blot showed that bFGF activated AKT/HIF-1α/VEGF signaling pathway.CONCLUSION:Intraperitoneal injection of bFGF reduces myocardial fibrosis and improves cardiac function in myocardial infarction mice.bFGF may promote angiogenesis by activating AKT/HIF-1α/VEGF signaling pathway.

OBJECTIVETo investigate the role of heme oxygenase-1 (HO-1) and its catalyst carbon monoxide (CO) in the development of myocardial damage and the effects of zinc protoporphyrin IX (ZnPPIX), an inhibitor of HO-1 on myocardium of mice with acute viral myocarditis.

METHODSA total of 112 inbred male Balb/C mice 4 - 6 weeks of age were divided randomly into 3 groups: the control group (C group, n = 32), the viral myocarditis group (V group, n = 40) and ZnPPIX group (Z group, n = 40). The Z and V groups were inoculated intraperitoneally (i.p.) with 0.1 ml of 10(-4.36) tissue culture infectious dose 50% (TCID(50))/ml Coxsackie virus B3 (CVB(3)) to produce viral myocarditis model on day 0, C group was injected i.p. with virus-free 1640 culture culture medium 0.1 ml at the same time, then operation was done as follows: the mice of group C and group V were injected i.p. with 0.1 ml NS each day. The mice of group Z were injected i.p. with 40 micromol per kilogram of body weight ZnPPIX (HO-1 inhibitor) qod. Eight mice of each group were sacrificed on days 4, 8, 15 and 21, respectively. The blood specimens were collected by taking out the eyeballs to test for the content of carboxyhemoglobin (COHb) using spectrophotometry and cardiac troponin I (cTnI) using chemiluminescent immunoassay. The hearts tissue slides were also stained by immunohistochemistry (IHC) for HO-1 and in situ hybridization (ISH) for HO-1 mRNA. The histological and ultrastructural changes were observed under light and electron microscopes.

RESULTS(1) The histopathological changes of myocardial cells: in the V and Z groups myocardial inflammatory cells infiltration reached the peak on day 8, the Z group histopathological scores were significantly lower than those in V group on day 8 (2.40 +/- 0.31 vs. 1.73 +/- 0.24, P < 0.01) and on day 15 (1.78 +/- 0.29 vs. 1.43 +/- 0.23, P < 0.05). No inflammation was present in group C. (2) The changes of serum cTnI level in both V and Z groups were significantly higher than those in C group on day 4, 8 and 15 (P < 0.01). The level in Z group was significantly lower than that in V group on day 4 [(6.074 +/- 1.475) ng/ml vs (7.911 +/- 1.225) ng/ml, P < 0.05] and day 8 [(0.821 +/- 0.294) ng/ml vs (1.480 +/- 0.454) ng/ml, P < 0.05]. (3) The changes of blood COHb level: compared with V group, in Z group the COHb level was lower on day 4 (P < 0.05) and day 15 (P < 0.01) after CVB(3) inoculation. Surprisingly, in Z group COHb level elevated suddenly on day 8 and showed conspicuously higher than that of V group (P < 0.01). (4) The result of HO-1 IHC staining: in both V and Z group myocardial cells had positive expression, while C group did not. (5) The results of HO-1 ISH were similar to those of HO-1 IHC, the A values of group Z was significantly lower than that of group V on day 4, 15 and 21(P < 0.01), but on day 8 it was higher than that of group C (P < 0.05).

CONCLUSIONHO-1 inhibitor, ZnPP not only could inhibit HO-1 overexpression but also could induce HO-1 expression temporarily and protect against myocardial injury at the early stage of acute viral myocarditis.

Animals ; Heme Oxygenase-1 ; antagonists & inhibitors ; Male ; Mice ; Mice, Inbred BALB C ; Myocarditis ; enzymology ; metabolism ; pathology ; virology ; Myocardium ; pathology ; ultrastructure ; Protoporphyrins ; pharmacology ; Virus Diseases ; metabolism ; pathology

OBJECTIVEIrinotecan (CPT-11), a specific inhibitor of topoisomerase I, has been proven to be effective in the treatment of refractory or metastatic colorectal cancer. Furthermore, several first line phase III trials of the combination therapy (FOLFIRI) using CPT-11 and fuorouracil/leucovorin (5-Fu/LV) were reported to have significant improvement in treatment result. Therefore, we designed a multicenter clinical study to observe the overall survival (OS), time to death (TTD), time to progression (TTP), efficacy and safety of FOLFIRI regimen for patients with refractory or metastatic colorectal cancer after first line chemotherapy failure.

METHODSPatients with metastatic or refractory colorectal cancer after first line oxaliplatin-based chemotherapy failure were enrolled into this prospective, one arm and open-labeled multicenter study. Irinotecan 180 mg/m2 was administered biweekly on D1, LV 200 mg/m2 by intravenous infusion in 2 hours before bolus intravenous injection of 5-Fu 400 mg/m2, then followed immediately by intravenous infusion of 5-Fu 2.4 g/m2 in 46 hours. OS, TTD, TTP, response rate (RR) and adverse events were assessed according to RSCIST criteria and NCIC-CTG CTCAE (3.0).

RESULTSSixty-six patients were valuable for safety assessment and and 61 for efficacy. There was no CR patient in this series. Ten patients had PR, 35 SD (57.4% ) and 16 PD (26.2%) with a response rate of 16.4% (10/61). The median TTP was 5.0 months (1-12 months), median TTD 9.9 months (5-27 months)and median OS 18.2 months (7-33 months). The adverse events including nausea,vomiting, anorexia,diarrhea, leucopenia and cholinergic syndrome were frequent, but usually in I - II degree. The rate of III/IV degree diarrhea and leucopenia was 7.6% and 22.7%, respectively.

CONCLUSIONThe regimen of irinotecan plus fuorouracil/leucovorin (FOLFIRI) is effective and well-tolerated as a second-line chemotherapy and may prolong the overall survival for the patient with refractory or metastatic colorectal cancer.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Camptothecin ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Colonic Neoplasms ; drug therapy ; pathology ; Disease Progression ; Female ; Fluorouracil ; adverse effects ; therapeutic use ; Follow-Up Studies ; Humans ; Leucovorin ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Neutropenia ; chemically induced ; Prospective Studies ; Rectal Neoplasms ; drug therapy ; pathology ; Remission Induction ; Survival Rate ; Vomiting ; chemically induced ; Young Adult

Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) is the most abundant kinase within excitatory synapses in the mammalian brain. It interacts with and phosphorylates a large number of synaptic proteins, including major ionotropic glutamate receptors (iGluRs) and group I metabotropic glutamate receptors (mGluRs), to constitutively and/or activity-dependently regulate trafficking, subsynaptic localization, and function of the receptors. Among iGluRs, the N-methyl-D-aspartate receptor (NMDAR) is a direct target of CaMKII. By directly binding to an intracellular C-terminal (CT) region of NMDAR GluN2B subunits, CaMKII phosphorylates a serine residue (S1303) in the GluN2B CT. CaMKII also phosphorylates a serine site (S831) in the CT of α-amino-3-hydroxy-5- methylisoxazole-4-propionic acid receptors. This phosphorylation enhances channel conductance and is critical for synaptic plasticity. In addition to iGluRs, CaMKII binds to the proximal CT region of mGluR1a, which enables the kinase to phosphorylate threonine 871. Agonist stimulation of mGluR1a triggers a CaMKII-mediated negative feedback to facilitate endocytosis and desensitization of the receptor. CaMKII also binds to the mGluR5 CT. This binding seems to anchor and accumulate inactive CaMKII at synaptic sites. Active CaMKII dissociates from mGluR5 and may then bind to adjacent GluN2B to mediate the mGluR5-NMDAR coupling. Together, glutamate receptors serve as direct substrates of CaMKII. By phosphorylating these receptors, CaMKII plays a central role in controlling the number and activity of the modified receptors and determining the strength of excitatory synaptic transmission.
Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; metabolism ; Neuronal Plasticity ; Phosphorylation ; Receptor, Metabotropic Glutamate 5 ; metabolism ; Receptors, Metabotropic Glutamate ; metabolism ; Receptors, N-Methyl-D-Aspartate ; metabolism ; Serine ; metabolism ; Synapses ; Synaptic Transmission

OBJECTIVETo investigate the effect of plasma homocysteic acid (HCA) reduction on serum C-reactive protein (CRP) level in children with Kawasaki disease (KD).

METHODSSeventy-six children with KD were divided into 2 equal groups for treatment with aspirin and IVIG, or with vitamin B6 and folic acid besides in addition to aspirin and IVIG. Serum CRP level was tested before and after the treatments, and plasma HCA level was also measured after the treatments.

RESULTSSerum CRP level was comparable between the two groups before the treatment, but significantly reduced after vitamin B6 and folic acid treatment (7.56-/+2.94 mg/L vs 12.23-/+4.16 mg/L, P<0.05). Additional vitamin B6 and folic acid treatment significantly lowered plasma HCA level (4.56-/+1.14 micromol/L vs 7.79-/+1.79 micromol/L, P<0.05), and correlation analysis demonstrated a positive correlation between plasma HCA and serum CRP levels (r=0.697, P<0.01).

CONCLUSIONLowering plasma HCA can decrease serum CRP in children with KD to enhance the therapeutic effect.

Aspirin ; therapeutic use ; C-Reactive Protein ; analysis ; Child ; Child, Preschool ; Female ; Folic Acid ; therapeutic use ; Homocysteine ; analogs & derivatives ; blood ; Humans ; Immunoglobulins, Intravenous ; therapeutic use ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome ; blood ; drug therapy ; Vitamin B 6 ; therapeutic use

Objective:To investigate the risk factors and their warning value for the occurrence of sepsis in patients with severe multiple trauma.Methods:A retrospective cohort study was conducted to analyze the clinical data of 92 patients with severe multiple trauma admitted to Yuyao People′s Hospital from July 2019 to October 2021. There were 71 males and 21 females, with the age range of 36-55 years [(45.5±13.6)years]. The injury severity score (ISS) was 20-29 points [(25.3±6.4)points]. The patients were divided into sepsis group ( n=32) and non-sepsis group ( n=60) according to whether sepsis occurred during hospitalization. Data were recorded for the two groups, including gender, age, basic diseases, cause of injury, number of injury sites, ISS, post-injury complications, and levels of aryl hydrocarbon receptor (AHR), C-reactive protein (CRP) and procalcitonin (PCT) at 1, 3 and 5 days after injury. The above data were analyzed to identify their correlation with the occurrence of sepsis in patients with severe multiple trauma by univariate analysis. The independent risk factors for sepsis in patients with severe multiple trauma were determined by multivariate Logistic regression analysis. The warning value of the single or combined risk factors for the occurrence of sepsis in patients with severe multiple trauma was evaluated by the receiver operating characteristic (ROC) curve and area under the curve (AUC). Results:By univariate analysis, it was demonstrated that the occurrence of sepsis was correlated with ISS, level of AHR at day 1 after injury, level of CRP at day 3 after injury and level of PCT at day 3 after injury ( P<0.05 or 0.01), but not with age, sex, basic diseases, level of AHR at 3, 5 days after injury, level of PCT at 1, 5 days after injury and level of CRP at 1, 5 days after injury (all P>0.05). By multivariate Logistic regression analysis, higher ISS ( OR=1.12, 95% CI 1.01, 1.24, P<0.05), level of AHR at day 1 after injury ( OR=1.30, 95% CI 1.10, 1.52, P<0.01) and level of PCT at day 3 after injury ( OR=1.81, 95% CI 1.08, 3.03, P<0.05) were found to be strongly correlated with the occurrence of sepsis. ROC curve analysis showed that higher ISS (AUC=0.69, 95% CI 0.57, 0.76) and level of AHR at day 1 after injury (AUC=0.79, 95% CI 0.68, 0.90) had warning value for the occurrence of sepsis, and the warning efficiency of combined panel was much better (AUC=0.86, 95% CI 0.77, 0.95). Conclusions:Higher ISS, level of AHR at day 1 after injury and level of PCT at day 3 after injury are independent risk factors for the occurrence of sepsis in patients with severe multiple trauma. ISS, AHR and combination of both exhibit good warning value for the occurrence of sepsis in patients with severe multiple trauma.