Protective Roles of Bacillus licheniformis Preparation Against Gastrointestinal Dysfunction and Inflammation After Radiotherapy in Children With Medulloblastoma.

Background The pathological foundation of diabetic retinopathy is the breakdown of the bloodretina barrier induced by multifactors.Objective This study was to investigate the retinal morphologic change and the levels of serum vascular endothelial growth factor(VEGF),endothelin(ET)and nitric oxide(NO)in diabetic rats.Methods Forty healthy female SD rats were randomly divided into experimental group and control group and 20 rats for each group.Acute diabetes models were established by the intraperitoneal injection of 60 mg/kg streptozotocin in experimental group and the equal volume of buffer solution was injected at the same way in the control group.The serum VEGF level,ET level and NO concentration of diabetic and control rats were detected using ELISA double antibody sandwich method,125I radioimmune method and nitrate reduction method respectively at 2,4,6 and 8 weeks after injection.The eyeballs of rats were enucleated at the eighth week for retinal pathologic examination.This experiment followed the Measures for the administration of experimental animals of Shanghai City.Results The retinal structure was normal throughout the experimental duration in the control group.However,retinal edema and cellular disorganization appeared at 4 months and retinal blooding could be seen with the extending of diabetes course.The levels of serum VEGF and ET in each experimental group were significantly higher than those in control groups(P＜0.05).The levels of serum NO elevated in 2-month experimental group compared with same-phase control group(Z =-2.193,P＜0.05),and those in 6-and 8-month experimental groups were significantly lower than in corresponding control groups(Z =-2.449,Z =-2.236,P＜0.05).With the progression of the disease,the levels of VEGF and ET increased gradually,but the levels of NO decreased gradually,showing statistically significant differences(P＜0.05).The level of serum VEGF showed a positive correlation with serum ET level and a negative correlation with the serum NO concentration(r=-0.814,r=-0.803,P＜0.01)in the experimental group.A negative leaner relation was also found between serum ET level and serum NO concentration(r=0.821,P＜0.01).Conclusions The serum VEGF,ET and NO levels are closely associated with the degree of retinal lesion in early diabetic models.These results suggest that serum VEGF,ET and NO levels may be the important indexes predicting the course of retinal disease in diabetic rats. Key words: Diabetes mellitus; Retina; Vascular endothelial growth factor; Endothelin; Nitric oxide

Objective This study aims to investigate the role of endothelin-1 (ET-1) and C-reactive protein (CRP) in restenosis after intervention of lower extremity arteriosclerosis obliterans. Methods The present prospective observational study included a total of 251 patients with arteriosclerosis obliterans in the lower extremity. All patients were treated with balloon dilatation, stent-assisted angioplasty or balloon dilatation, and stent-assisted angioplasty. Furthermore, these patients received a CTA examination at one and three months after surgery. The serum ET-1 and CRP levels were determined using a commercial enzyme-linked immunosorbent assay (ELISA). Results In non-restenosis patients, both the CRP and ET-1 levels were significantly upregulated after surgery, reached a peak level at one week, and decreased at one month after surgery. However, for restenosis patients, the serum ET-1 and CRP levels did not decrease to the baseline at one and three months after surgery, but were remarkably higher than the levels for non-restenosis patients. Serum ET-1 levels were positively correlated with serum CRP levels at both one and three months after surgery. Both ET-1 and CRP levels after one week and one month, and CRP at three days, one week, one month and three months after surgery were risk factors for restenosis after intervention surgery of arteriosclerosis obliterans. Conclusion Both serum ET-1 and CRP levels were elevated after one and three months of intervention for lower extremity arteriosclerosis obliterans in patients with restenosis. These might be the risk factors for restenosis of lower extremity arteriosclerosis obliterans patients.

Transforming growth factor beta (TGF-β) is a cytokine with important involvement in biological processes related to the pathogenesis of sickle cell disease (SCD), including endothelial and vascular dysfunction, inflammation, and hematopoietic homeostasis. This study is aimed at investigating associations between levels of TGF-β1 and classical laboratory biomarkers and inflammatory mediators, as well as the tissue inhibitor of metalloproteases-1 (TIMP-1) and matrix metalloproteinase-9 (MMP-9), in pediatric patients (n = 123) with SCD in steady state: 84 with sickle cell anemia (HbSS) and 39 with hemoglobin SC disease (HbSC). A healthy control (HC) group of 59 individuals was also included. Hematological and biochemical analyses were carried out using electronic methods. TGF-β1, TIMP-1, and MMP-9 plasma quantifications were performed by ELISA. TGF-β1 plasma levels were higher in HbSS individuals than in HbSC and HC. In individuals with HbSS, TGF-β1 levels were positively correlated with red blood cells, hemoglobin, hematocrit, platelets, and TIMP-1. In addition, HbSS individuals with TGF-β1 levels above the median (≥72.29 ng/mL) also presented increased monocyte counts and decreased albumin levels. In patients with HbSC, TGF-β1 levels were positively correlated with leukocytes, eosinophils, lymphocytes, monocytes, and platelets, as well as levels of TIMP-1, VLDL-C, triglycerides, heme, and AST. Additionally, HbSC individuals with TGF-β1 levels above the median (≥47.80 ng/mL) presented increased leukocyte and platelet counts, as well as increased levels of triglycerides, VLDL-C, MMP-9, and TIMP-1, and decreased HDL-C. Our findings suggest that TGF-β1 may play important roles in vascular remodeling, vasculopathy, angiogenesis, and inflammation in pediatric patients with SCD.

Sir, Protein-energy malnutrition (PEM) is one of the leading causes of childhood morbidity and mortality in developing countries. The case-fatality rate for PEM was 28.4% despite hospitalization (1). Magnesium (Mg) modulates vasomotor tone, blood pressure, and peripheral blood flow. Mg deficiency was shown to trigger vasoconstriction and enhance vascular endothelial injury (2). On the other hand, endothelin-1 (ET-1) is a potent vasoconstrictor peptide, produced by vascular endothelial cells (3). We investigated the effects of hypomagnesaemia on mortality and other mortality risk factors in patients with PEM. The study included 25 children with PEM. Their mean age was 4.7+2.9 months. In the study groups, malnutrition was not related to malabsorption. Malnutrition was diagnosed using the Wellcome classification. All children had severe malnutrition without malabsorption (mean weight-for-height z-score was −3.1). Weights were measured using the same equipment by the same observer. Weights were measured to the nearest 10 g using a digital electronic instrument (Seca 727 Digital Baby Scale, serial interface RS 232, Seca Corporation, VogelH Catalog No. 900-022). Mann-Whitney U tests and odds ratio were used for the comparison of means of each group and for ratios of each group respectively. Informed consent was obtained from parents. The Ethics Committee of the Faculty approved the study. Serum Mg and ET-1 levels of the patients with PEM were prospectively evaluated. During the follow-up period, four (16%) patients died within four days after admission. Although serum Mg levels were significantly lower in the patients who died, serum ET-1 levels were slightly higher at admission (Table). Serum Mg levels were lower than normal value in three (75.0%) of the four deceased and in six (28.6%) of the 21 surviving patients with PEM. The odds ratio (odds ratio=(3/1)/(6/15)=7.5) for mortality was 7.5 times higher in the malnourished children with hypomagnesaemia (n=9) than in the malnourished children without hypomagnesaemia (n=16). When the mean weight-for-height measurements of the deceased and the surviving patients were evaluated, no significant difference (p>0.05) was observed between them. Table. Mean±SD and significance values for serum Mg and ET-1 levels in the surviving and deceased patients with PEM We found significant differences in serum Mg levels but not in serum ET-1 levels between the surviving and the deceased groups of patients with PEM. Serum Mg levels were significantly lower in the paediatric patients (68.8%) in the intensive care unit compared to the control group (12.0%) (p<0.001) (4). Furthermore, Mg intake from drinking-water was suggested to exert a significant protective effect on the risk of cerebrovascular disease and death from stroke (5). Mg is one of the most abundant ions in human cells, and its serum concentration is remarkably constant in healthy subjects. Although the measurement of serum Mg does not always reflect the overall status of Mg metabolism, serum Mg correlates well with intracellular-free Mg, the physiological active form of the elements (6). However, even small alteration in the extracellular Mg concentration can influence human organism and metabolism. When ET-1 levels were investigated as a mortality risk factor, Kunz et al. reported that plasma ET-1 levels were slightly higher but not significant in haemodialyzed patients with cardiovascular history compared to haemodialyzed patients without cardiovascular history (7). Adversly, plasma ET-1 concentrations are strongly related to outcome after acute myocardial infarction (p<0.0001) and provide prognostic information independent of clinical and biochemical variables. On the other hand, an experimental study showed that magnesium deficiency was associated with increased ET-1 levels and with significant proaggregatory and coagulation alterations (8). When Serebruany et al. investigated alterations in various haemostatic factors as risk factors for survival after acute myocardial infarction (9), no significant differences was found in the ET-1 plasma concentrations during occlusion between the surviving and the non-surviving groups in this study, although plasma baseline ET-1 levels was slightly higher but not significant in the deceased swine (9). This result was similar to ours. However, results of a previous study showed that the mean serum ET-1 levels in the group with low magnesium levels were significantly higher than that of the group with normal magnesium levels (p<0.05) in malnourished children (10). This discrepancy in our results may be related to the low number of the deceased patients with PEM. On the other hand, it has been shown a release of TNFα and IL-1 at approximately one week after the administration of a low Mg diet in mice (11). Results of another study showed that hypomagnesaemia could stimulate endothelial cells to produce and release ET-1 (12). So, the sampling time may be also important. Since the number of cases chosen was small in our study, additional studies on pathophysiology and clinical importance of hypomagnesaemia are needed. The findings of the present study calls for giving attention to hypomagnesaemia as a mortality risk factor in PEM.

To observe the effect of Fu's subcutaneous needling in the treatment of non-acute idiopathic facial paralysis and its effect on serum levels of nitric oxide (NO) and endothelin (ET). A total of 76 patients with non-acute idiopathic facial paralysis were randomly divided into an observation group (38 cases, 2 cases dropped out) and a control group (38 cases, 2 cases dropped out). The patients in the control group received basic treatment (mecobalamin tablets orally, specific electromagnetic spectrum irradiation, facial muscle rehabilitation training). The patients in the observation group were treated with Fu's subcutaneous needling on the basis of the control group. The needling points included brachioradialis muscle, sternocleidomastoid muscle, trapezius muscle, etc., and the needling was inserted around the affected muscle, and the reperfusion activity was carried out at the same time, once every other day, 3 times a week. Both groups were treated for 4 weeks. The House-Brackmann (H-B) grade and H-B symptom score were observed before treatment, after 2 and 4 weeks of treatment in the two groups. The facial disability index (FDI) score [including physical function (FDIP) score and social life function (FDIS) score] and the serum levels of NO and ET were compared before and after 4 weeks of treatment in the two groups. The clinical effect and safety of the two groups were assessed. After 2 and 4 weeks of treatment, the H-B grade of the two groups was lower than that before treatment, and the H-B symptom scores were higher than those before treatment (P<0.001, P<0.05); the H-B grade of the observation group was lower than that of the control group, and the H-B symptom score was higher than that of the control group (P<0.01, P<0.05). After 4 weeks of treatment, the FDIP scores of the two groups were higher than those before treatment, and the FDIS scores were lower than those before treatment (P<0.05 ); the FDIP score of the observation group was higher than that of the control group, and the FDIS score was lower than that of the control group (P<0.05). After 4 weeks of treatment, the serum level of NO in the observation group was higher than that before treatment, and the serum level of ET was lower than that before treatment (P<0.05); the increase of serum level of NO and the decrease of serum level of ET in the observation group were greater than those in the control group (P<0.05). The cure rate of the observation group was 55.6% (20/36), which was higher than 22.2% (8/36) of the control group (P<0.05). There were no serious adverse reactions in both groups. Fu's subcutaneous needling combined with basic treatment can effectively improve the motor function of facial muscles in patients with non-acute idiopathic facial paralysis, which may be related to the regulation of serum NO and ET levels.

Endoscopic evaluation is the gold standard for monitoring the disease activity in inflammatory bowel disease (IBD) but the procedure is invasive and not appropriate for frequent use, especially in the paediatric population. The aim of the present study was to assess the correlation between the levels of several inflammatory biomarkers and the degree of intestinal inflammation in paediatric patients with IBD. A single center study including 31 children with ulcerative colitis (UC) and 22 children with Crohn's disease (CD) with different disease duration and activity. All participants provided blood samples to measure the levels of white blood cell count, platelets, C-reactive protein, erythrocyte sedimentation rate, albumin and fibrinogen, and faecal samples for measurement of faecal calprotectin and faecal alpha-1 antitrypsin. All participants underwent endoscopic evaluation. Endoscopic disease activity was assessed according to the Mayo Endoscopic Subscore and Simple Endoscopic Score for Crohn's Disease in UC and CD patients, respectively. 135 visits were included: 73 for UC patients and 62 for CD patients. In UC patients the strongest correlation was between the Mayo Endoscopic Subscore and the faecal calprotectin (r=0.867, p<0.001) followed by the albumin (r=0.523, p<0.001) and the C-reactive protein (r=0.487, p<0.001). In CD the strongest correlation was between the Simple Endoscopic Score for Crohn's disease and the faecal calprotectin (r=0.872, p<0.001) followed by the C-reactive protein (0.708, p<0.001) and the erythrocyte sedimentation rate (0.605, p<0.001). The faecal calprotectin is a valuable surrogate marker of intestinal inflammation that is useful for monitoring of a disease activity in paediatric patients with IBD.

<h3>Background</h3> SNV are severe inflammatory disorders with highly variable course of disease after initial treatment. New biomarkers are needed for SNV because the existing markers such as anti-neutrophil cytoplasmic antibodies...

High-sensitivity C-reactive protein and endothelin-1 in age-related macular degeneration

Magnetic resonance (MR) enterography has the advantage over other techniques of being noninvasive, lacking ionizing radiation, and demonstrating excellent soft-tissue contrast to evaluate pediatric patients with inflammatory bowel disease (IBD). To evaluate the diagnostic performance of MR enterography for detection of active inflammation in children and adolescents with known or suspected IBD. A search of MEDLINE and EMBASE up to January 2, 2017, was performed to identify studies. Search terms included child, pediatric, adolescent, Crohn disease, inflammatory bowel disease, and magnetic resonance enterography. The search was limited to English-language publications. Studies evaluating the diagnostic performance of MR enterography for detection of active inflammation in pediatric patients with known or suspected IBD were selected. Two reviewers independently assessed the eligibility of the selected articles. The study was performed and reported in accordance with the PRISMA guidelines. Pooled summary estimates of sensitivity and specificity were calculated using hierarchical logistic regression modeling. The diagnostic performance of MR enterography for detection of active inflammation in pediatric patients with known or suspected IBD was the primary outcome. Subgroup analyses and meta-regression were performed. Eighteen original articles involving a total of 687 patients were included. The summary sensitivity was 83% (95% CI, 75%-89%), the summary specificity was 93% (95% CI, 90%-95%), and the area under the hierarchical summary receiver operating characteristic curve was 0.95 (95% CI, 0.93-0.97). The Higgins I2 statistics demonstrated substantial heterogeneity in terms of sensitivity (I2 = 84.1%) and specificity (I2 = 68.8%). Based on per-patient analysis, the summary sensitivity was 86% (95% CI, 78%-91%) and specificity was 91% (95% CI, 82%-96%). In meta-regression, among the various potential covariates, scanner manufacturer was associated with study heterogeneity. Magnetic resonance enterography, which is a noninvasive, radiation-free modality, demonstrates high diagnostic performance in the diagnosis of active inflammation in pediatric patients with IBD, especially at the per-patient level.

The diagnostic performance of diffusion-weighted imaging magnetic resonance enterography [DWI-MRE] has not been clearly established in a paediatric population. We systematically evaluated the diagnostic performance of DWI-MRE for the detection of bowel inflammation in paediatric patients with suspected or known inflammatory bowel disease [IBD]. MEDLINE/PubMed, EMBASE, Web of science and the Cochrane library were searched for articles investigating the diagnostic performance of DWI-MRE for the detection of bowel inflammation in paediatric patients with suspected or known IBD up to December 31, 2020. Pooled sensitivity and specificity were calculated using a bivariate random-effects model. Pooled inter-reader agreement for the interpretation of DWI-MRE was also calculated. This study was registered as PROSPERO CRD42021228754. Nine studies covering 400 paediatric patients were included. The pooled sensitivity and specificity of DWI-MRE for the detection of bowel inflammation were 0.93 (95% confidence interval [CI], 0.88-0.96) and 0.96 [95% CI, 0.87-0.99], respectively. Substantial heterogeneity was noted in both sensitivity [I2 = 66%; p < 0.01] and specificity [I2 = 94%; p < 0.01]. Meta-regression analysis identified that the use of spasmolytics contributed to higher specificity [0.89-0.99] and that quantitative assessment with an apparent diffusion coefficient cut-off value contributed to lower sensitivity [0.93-0.85] and specificity [0.98-0.72]. The pooled coefficient of inter-reader agreement, including four studies using visual assessment, was 0.97 [95% CI, 0.78-1.00]. DWI-MRE, especially when used with spasmolytics, is accurate for the detection of bowel inflammation in paediatric patients with suspected or known IBD. Quantitative measurement of ADC is not practical for this purpose.

Cardiovascular Disease in Children with Chronic Kidney Disease

We have investigated serum endothelin-1 (ET) and nitric oxide (NO) levels before and after a short course of high dose methylprednisolone (HDMP) in children with acute lymphoblastic leukemia (ALL) as an indicator of vasoconstrictor and vasodilator properties of endothelium. Nineteen children with ALL (aged 13-180 months; 5 girls and 14 boys) and 25 healthy children were included in the present study. The children with ALL were given HDMP (20 mg kg 1 day 1) alone for the first 5 days. Serum ET and NO levels were analysed before and after a short course of high dose methylprednisolone. Before treatment, serum ET levels (median 7.6 pg ml 1) of the patients were lower than the healthy controls (13.0 pg ml 1) (p < 0.05), and it rose to similar levels (13.0 pg ml 1) following therapy as in the controls. Nitric oxide levels (7.0 micromol) of the patients were insignificantly higher than the healthy controls (3.9 micromol) and did not differ after treatment (7.0 micromol) (p > 0.05). In conclusion, the elevation of ET to normal level following treatment suggests that a short course of high dose of methylprednisolone improve the endothelial dysfunction caused by acute leukemia.

<h3></h3> Children with inflammatory bowel disease (IBD) have significantly lower health related quality of life (HRQoL) compared to healthy controls. HRQoL presents a broad, multidimensional concept compromising one’s physical health, psychological state, level of independence, social relationships, personal beliefs and relationship to the environment. Good sleep is essential in maintaining health and quality of life (QoL) and plays a role in regulation of immune and neuroendocrine system. The aim of our study was to evaluate the relationship between sleep quality and HRQoL in children with IBD in remission. A total of 33 paediatric IBD patients in remission (20 boys) aged 15.6 ± 1.9 years were included in the study (disease type: Crohn’s disease (CD), n=16, ulcerative colitis (UC), n=15, inflammatory bowel disease-unclassified (IBD-U), n=2). Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) questionnaire, whilst HRQoL was assessed using IMPACT III questionnaire. Moreover, patients wore a triaxial accelerometer for five consecutive days for objective PA quantification. Anthropometric data and inflammatory markers’ values such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and faecal calprotectin values were recorded. Prevalence of impaired sleep quality (PSQI&gt;5) was 36.4%, with mean PSQI score 4.64±2.21. Highest mean scores were recorded in the sleep duration (mean score 1.06±0.99), sleep disturbance (mean score 1.06±0.35) and daytime dysfunction (mean score 1.00±0.79) components of the questionnaire. Mean IMPACT III score was 146.36±17.24. On average, patients spent 38 minutes in moderate-to-vigorous physical activity (MVPA), and 198 minutes in light physical activity (LPA) per day. PSQI score negatively correlated with IMPACT III score (coef. -0.446, p&lt;0.01); meaning that the more significantly impaired sleep quality the more impaired QoL; and with time spent in LPA (coef. -0.482, p &lt;0.01). Interestingly, faecal calprotectin only positively correlated with sleep disturbance score (coef. 0.352, p =0.048), but had no significant correlation with the total PSQI score. No correlation was found between anthropometric and other laboratory parameters, MVPA and PSQI and IMPACT III scores. More than a third of paediatric IBD patients suffer from poor sleep quality even in the remission phase. Further studies investigating the relationship between sleep quality, HRQoL and possible presence of subclinical inflammation in paediatric patients with IBD are warranted.

Objective To investigate the effects of estrogen replacement therapy on the serum nitric oxide and endothelin-1 level of ovariectomized rat.Methods The ovariectomized animal model and estrogen replacement therapy rat were established,thirty female rats were randomly divided into three groups:group A,ovariectomy;group B,ovariectomy plus estrogen replacement therapy;group C,sham-ovariectomy.The rats were killed after two months.The serum nitric oxide and endothelin-1 level were determined.Results In group A,the serum nitric oxide level was lower as compared with group C,but the serum endothelin-1 level was higher than those in group C.In group B,the serum nitric oxide level was higher and the serum endothelin-1 level was lower than those in group A.Conclusions Estrogen could modulate the productions of the nitric oxide and the endothelin-1 in the vascular endotheliocytes and improve the function of the vascular endothelial cells,which may be a bases of the benificial effect of estrogen in the prevention of atherosclerosis.

Abstracts