Abstract:

Pulmonary arterial hypertension (PAH) is one of the most severe complications of congenital heart defects with left to right shunt. Pulmonary vascular remodeling (PVR) is extremely essential in PAH. Therefore, prevention and reversion of PVR is one of the most important factors for improving quality of life for children suffering from PAH. In this article we reviewed the emerging research views on PVR from the disciplines of oncology and anti-tumor pharmacy. Two main sections were included. On the one hand, we introduced the "ATM signal turning point hypothesis" from the DNA damage response (DDR) mechanism research in oncology. The hypothesis suggests that the tumor-like proliferation of vascular smooth muscle cells might be the pathological basis of obstructive PAH. On the other hand, a new lung-targeted drug delivery system based on the fact that low concentration of anti-tumor drugs can inhibit angiogenesis without cellular toxicity was introduced. These new research directions could extend current practice in PVR therapy.

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OBJECTIVE: Congenital heart disease (CHD) is a chronic illness with a high frequency in the worldwide population, and is normally diagnosed at birth or in uterus. Because of better conditions in diagnosis and early medical and surgical treatment, patients have survival rates of 90% and go further and further in life, facing different challenges in life cycle. In this study, we tested the effects of different demographic, clinical and psychosocial variables on the perception of quality of life (QOL), on psychosocial adjustment (PSA) and psychiatric morbidity (PM) of adolescents and young adults with CHD. We aimed to evaluate QOL, PM and PSA of adolescents and young adults with CHD and to determine which variables (demographic, clinical, and psychosocial) play a role in buffering stress and promoting resilience and which ones have a detrimental effect. METHODS: The study enrolled 150 CHD patients (87 males and 63 females), 12 to 26 years (17.45±3.373 years). The participants were interviewed regarding social support, family educational style, self-image, demographic information and physical limitations. They responded to questions in a standardized psychiatric interview (SADS-L) and completed self-reports questionnaires for assessment of QOL (WHOQOL-BREF) and PSA (YSR/ASR). ReESULTS: We found a 18.7% lifetime prevalence of psychopathology in our participants (25.4% in females and 13.8% in males). 57.1% had retentions in school (1.53±0.804 year). The perception of QOL of CHD patients is better compared to the Portuguese population in the social relationships, environmental, physical and general dimensions. However, it is worse in female CHD patients and patients with poor academic performance and social support as well as in patients with complex or cyanotic CHD, moderate-to-severe residual lesions and physical limitations, and undergoing surgery. All of these variables, except presence of cyanosis, are also associated to a worse PSA. CONCLUSIONS: Female patients and patients with poor academic performance and poor social support refer worse PSA and QOL.

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OBJECTIVE: To study the expression of histone acetyltransferases (HATs) and histone deacetylases (HDACs) in children with tetralogy of Fallot (TOF), and to investigate the role of histone acetylation and acetylation-related enzymes in the pathogenesis of TOF. METHODS: Myocardial tissue samples in the TOF group were obtained from 46 children with TOF who underwent radical operation, and myocardial tissue samples in the control group were obtained from 16 children who suffered accidental deaths and had no cardiac anomalies as shown by autopsy. The acetylation of H3K9, H3K18 and H3K27 was evaluated by immunohistochemistry. The mRNA expression of HATs and HDACs in the myocardium was measured by real-time PCR. The correlation between mRNA expression of HATs and HDACs and histone acetylation was analyzed. RESULTS: Compared with the control group, the TOF group showed significantly increased acetylation of H3K9 (P=0.0165) and significantly decreased acetylation of H3K18 (P=0.0048) and H3K27 (P=0.0084). As to 4 HATs and 6 HDACs, the mRNA expression of EP300 and CBP was significantly higher in the TOF group than in the control group (P=0.025; P=0.017), and there was no significant difference in the mRNA expression of other HATs and HDACs between the two groups. The correlation analysis revealed a positive correlation between H3K9 acetylation and mRNA expression of EP300 (r=0.71, P<0.01) and CBP (r=0.72, P<0.01). CONCLUSIONS: Upregulated mRNA expression of EP300 and CBP may be associated with increased H3K9 acetylation, suggesting that EP300 and CBP might affect cardiac development by regulating H3K9 acetylation.

Abstract:OBJECTIVE: To investigate the association between 2 SNPs of ISL1 gene and congenital heart disease (CHD) in Tianjin Han children. METHODS: Polymerase chain reaction and DNA sequencing were used to detect 2 SNPs at rs41268421 and rs1017 sites of ISL1 gene, including 35 CHD cases and 30 non-CHD controls. Differences of genotype and allele frequencies of rs41268421 and rs1017 sites were compared, and haplotype analysis of the two sites was performed. RESULTS: Three genotypes (GG, GT and TT) were detected at ISL1 gene SNP rs41268421, and three genotypes (AA, AT and TT) were detected at SNP rs1017. At rs41268421, GT+TT genotypes and T allele frequencies in the CHD group were statistically higher than in the controls. The risk of CHD in children with T allele was significantly increased compared with children with G allele (OR=4.833). At rs1017, AT+TT genotypes and T allele frequencies in the CHD group were statistically higher than controls. The risk of CHD in children with T allele was greater compared with children with A allele (OR=4.491; P<0.05). Four kinds of haplotype were detected in the two SNPs sites and TT type increased the risk of CHD (OR=7.813). CONCLUSIONS: Haplotype TT may increase the risk of CHD in Tianjin Han children.

Abstract:OBJECTIVE: To study the perioperative change in serum neutrophil gelatinase-associated lipocalin (NGAL) level among children with congenital heart disease (CHD) and pulmonary hypertension (PH) and its significance. METHODS: Eighty children with CHD were divided into four groups according to pulmonary artery systolic pressure: non-PH, mild PH, moderate PH and severe PH groups. Serum NGAL levels were measured before operation, immediately after operation and 24 hours after operation. The relationship of serum NGAL level with PH and early prognosis was analyzed. RESULTS: The mild, moderate and severe PH groups had significantly higher serum NGAL levels than the non-PH group, and the severer the PH, the higher the serum NGAL level (P<0.01). All groups showed significant decreases in serum NGAL levels after operation (P<0.01). Serum NGAL level was positively correlated with the degree of PH and length of stay in the intensive care unit (P<0.01). CONCLUSIONS: Serum NGAL level increases in children with CHD and PH, and it gradually decreases after operation for closing the abnormal shunt. Serum NGAL level may be used as a serological indicator for evaluating the degree of PH and surgical outcome.

Abstract:OBJECTIVE: To identify the risk factors for accelerated junctional escape rhythm (AJER) in children early after percutaneous ventricular septal defect (VSD) closure. METHODS: A retrospective controlled study was conducted on 42 children who had AJER within one week after percutaneous VSD closure between January 2008 and October 2012. These subjects were compared with controls without AJER after VSD closure in terms of age, sex, diameter of VSD, occluder size, difference between occluder size and diameter of VSD, and distance between VSD and aortic valve ring. Risk factors for AJER were identified by logistic regression analysis. RESULTS: Compared with the control group, the AJER group had a longer distance betweenVSD and aortic valve ring, a larger diameter of VSD (basal diameter), a larger occluder size (waist diameter) , and a bigger difference between the waist diameter of occluder and diameter of VSD (P<0.05). Logistic regression analysis showed that distance between VSD and aortic valve ring (OR=1.813, P<0.05) and occluder size (OR=1.671, P<0.05) are primary risk factors for AJER. CONCLUSIONS: AJER early after percutaneous VSD closure is related to diameter of VSD, occluder size, difference between the waist diameter of occluder and diameter of VSD, and distance between VSD and aortic valve ring. The distance between VSD and aortic valve ring and occluder size are primary risk factors for AJER.

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OBJECTIVE: Inadequate postnatal nutritional support is an important factor contributing to growth failure, which leads to poor neurological outcome. In this study, co-word analysis was used to investigate the research on nutrition of premature infants over the last six years in China, describe the research trend in this field in China, and provide possible directions for future research. METHODS: A literature search was performed in January 2013 using the CNKI database and the key words “preterm infant” and “nutrition”. A total of 772 articles were retrieved. Then high-frequency key words were extracted using Excel 2010 to create a co-occurrence matrix. Finally, a visualized network was built using Ucinet 6.0. RESULTS: The knowledge domain map of research on nutritional support for premature infants in China showed that the major topic of relevant research is still the combination of parenteral nutrition and enteral nutrition, with the goal of maintaining appropriate growth rates in premature infants. Researchers have paid much attention to the adverse effects of parenteral nutrition. Feeding intolerance is still the main problem in nutritional support, especially enteral nutrition, for premature infants. CONCLUSIONS: A visualized network of current research on nutrition of premature infants in China has been created, and a knowledge domain map has been drawn to reflect the hot topics in this field of study over the last six years.

Abstract:OBCTIVE: To observe changes in plasma thrombomodulin (TM) and D-dimer (DD) levels in neonates with sepsis, and to investigate their significance in evaluating the patients' condition and prognosis. METHOD: Fifty-six neonates with sepsis were classified into extremely critical (n=13), critical (n=22) and non-critical groups (n=21) based on neonatal critical illness score (NCIS). Fasting venous blood samples were collected on admission and in the recovery phase. Plasma TM and D-dimer levels were measured using enzyme-linked immunosorbent assay and immune turbidimetry, respectively. Twenty-six healthy neonates were selected as the control group. Plasma TM and D-dimer levels were compared between groups, and the changes after treatment were determined. RESULTS: Plasma TM levels in the extremely critical, critical and non-critical groups were 25.5±6.6, 17.3±4.7 and 13.3±2.8 μg/L respectively, significantly higher than in the control group (9.8±2.7 μg/L) (P<0.01). Plasma D-dimer levels in the extremely critical and critical groups were 744±262 and 436±147 μg/L respectively, also significantly higher than in the control group (205±61 μg/L) (P<0.01). The extremely critical group had significantly higher plasma TM and DD levels than the critical group (P<0.05), and the critical group had significantly higher plasma TM and DD levels than the non-critical group (P<0.05). All patients showed significant decreases in plasma TM and DD levels in the recovery phase after treatment (P<0.01). Plasma TM and DD levels were significantly negatively correlated with NCIS (r?=?-0.428, P<0.01; r?=?-0.363, P<0.01). CONCLUSIONS: Determination of plasma TM and DD levels may be helpful in evaluating severity and prognosis in neonates with sepsis.

Abstract:OBJECTIVE: To study the clinical features of bronchiolitis obliterans (BO) in children. METHODS: The clinical data of 28 children with BO between July 2007 and April 2012 was retrospectively reviewed. RESULTS: All patients presented with persistent or repeated cough and wheezing. Twenty-three cases were post-infectious bronchiolitis obliterans (PIBO), among whom the etiology were adenovirus (12 cases), measles (2 cases), influenza virus A (2 cases), mycoplasma pneumoniae (1 case), mycoplasma pneumoniae coinfection with adenovirus (1 case), respiratory syncytial virus coinfection with Parainfluenza type 3 virus (1 case) and pulmonary tuberculosis (1 case). The etiology of 3 cases was not associated with infection. The etiology was unknown in 2 cases. Pulmonary HRCT revealed that decreased density in 25 cases, mosaic perfusion in 21 cases, bronchial wall thickening in 15 cases, bronchiectasis in 12 cases and air retention in 6 cases. Lung function test was performed on 21 cases and demonstrated that obstructive ventilation disorder in all 21 cases. Bronchodilation test was performed on 18 cases and 17 cases showed a negative result. All 28 cases received corticosteroid treatment, and 24 cases were orally administered with low doses of azithromycin. One case died during hospitalization. Eighteen cases were followed up for 4 months to 4 years and seven months. Clinical manifestations were improved in 12 cases and one case died. CONCLUSIONS: Low respiratory infection is the most common cause of pediatric BO and adenovirus is a major pathogen. Persistent wheezing and cough were main clinical manifestations. Pulmonary HRCT imaging is important for diagnosis and follow-up of BO. Lung function test can typically show obstructive ventilation disorder. Corticosteroid and methotrexate may be effective for treatment of BO. Prognosis of this disease is unsatisfactory. Early diagnosis and treatment, and avoidance of repeated respiratory tract infection may be helpful to improve the prognosis.

Abstract:OBJECTIVE: To investigate the effect of low-dose methylprednisolone on serum tumor necrosis factor alpha (TNF-α) level in children with Mycoplasma pneumoniae pneumonia (MPP). METHODS: A case-control study was conducted among 38 children with MPP who received treatment in the Affiliated Hospital of Yan'an University between January and December 2012, and who had not received glucocorticoids before hospitalization. They were randomly divided into methylprednisolone treatment (n=20) and conventional treatment groups (n=18). The methylprednisolone treatment group was administered with methylprednisolone (1 mg/kg·d) by intravenous drip for three days in addition to conventional treatment. Serum samples were collected from both groups before treatment and on days 4 and 7 of treatment. Twenty-five children who underwent physical examination in the healthcare clinic during the same period were randomly selected as a normal control group, and serum samples were collected on the same day that the physical examination was performed. Serum TNF-α levels in the three groups were measured using enzyme-linked immunosorbent assay. RESULTS: On admission, the methylprednisolone treatment and conventional treatment groups had significantly higher serum TNF-α levels than the normal control group (P<0.01), but there was no significant difference between the methylprednisolone treatment and conventional treatment groups. On days 4 and 7 of treatment, the methylprednisolone treatment group had significantly lower serum TNF-α levels than the conventional treatment group (P<0.05; P<0.01). On day 7 of treatment, there was no significant difference in serum TNF-α level between the methylprednisolone treatment and normal control groups, but the conventional treatment group still had a significantly higher serum TNF-α level than the normal control group (P<0.01). CONCLUSIONS: Low-dose methylprednisolone can significantly decrease serum TNF-α level and inhibit inflammatory response in children with MPP, and may reduce damage caused by inflammatory response.

Abstract:OBJECTIVE: To investigate impact factors for the efficacy of specific immunotherapy (SIT) in children with dust mite allergic asthma. METHODS: Ninety-nine children with house dust mite allergic asthma received standardized SIT, and the level of asthma control was evaluated after 6 months (S1 stage), 12 months (S2 stage), 18 months (S3 stage), and 24 months (S4 stage) of treatment. The age of first visit, course of asthma, level of asthma severity, initial serum specific immunoglobulin E (sIgE) level, combination with allergic rhinitis or atopic dermatitis, use of inhaled corticosteroids, and local or systemic side effects during treatment were recorded, and their impacts on the level of asthma control were analyzed. RESULTS: As the SIT proceeded, the number of clinically controlled cases increased significantly (P<0.01). The level of asthma control was significantly affected by the age of patients at first visit in S1 and S3 stages, and combination with allergic rhinitis or atopic dermatitis in S1 stage (P<0.05). In all stages of SIT, the controlled cases had significantly higher initial serum sIgE levels than the uncontrolled cases (P<0.05). In S1 and S2 stages, there was a significantly higher proportion of controlled cases among children with a high level of asthma severity than among those with a low level of asthma severity (P<0.05). CONCLUSIONS: There is a positive correlation between long-term efficacy of SIT and the course or the total dose of treatment. Patients with higher initial serum sIgE levels achieve clinical control earlier than those with lower initial serum sIgE levels during SIT.

Abstract:OBJECTIVE: To assess the efficiency and safety of human neural progenitor cells (hNPCs) transplantation in the treatment of pervasive developmental disorder (PDD) in children. METHODS: Twenty-two children with PDD were treated, including 13 children with Rett syndrome and 9 children with autism. They accepted hNPCs transplantation voluntarily. hNPCs derived from aborted fetal tissue were injected into the lateral ventricle of the patients under supersonic guidance. All patients were assessed according to the Autism Behavior Checklist before operation, at one and six months post operation, and one year later. RESULTS: No delayed complications resulting from this therapy were observed. The clinical symptoms of 17 patients, including 8 patients with autism and 9 patients with Rett syndrome, improved in varying degrees. The assessment results of the Autism Behavior Checklist for children with autism showed that compared with pre-operative function, social communication scores were significantly reduced at six months after transplantation, and total scores and social communication and language scores were also significantly reduced 1 year after transplantation (P<0.05). CONCLUSIONS: These results suggest that hNPCs transplantation is effective and safe for treatment of PPD in children. It deserves a further study

Abstract:OBJECTIVE: To investigate the effects of sleep deprivation on intelligence development in primary school students. METHODS: Between June 2009 and April 2010, 316 grade 5 students aged 10-11 years were selected from four primary schools in four administrative districts of Changsha, China by stratified random sampling. The intelligence characteristics of children with varying degrees of sleep deprivation were investigated using the Chinese Wechsler Intelligence Scale for Children. RESULTS: A total of 286 valid questionnaires were received, with a response rate of 90.5%. The survey was comprised of a sleep deprivation group (sleep time <8 hours per night; n=180) and a control group (sleep time ≥8 hours per night; n=106). The sleep deprivation group had significantly lower subtest scores, verbal intelligence quotient (IQ) (VIQ), performance IQ (PIQ) and full scale IQ (P<0.05) and significantly lower verbal comprehension factor score and memory/attention factor score compared with the control group (P<0.05). Compared with the control group, the moderate sleep deprivation subgroup had significantly decreased VIQ and full scale IQ as well as verbal comprehension factor score and memory/attention factor score (P<0.05), and the severe sleep deprivation subgroup showed decreases in all scores (P<0.05). The sleep deprivation group and moderate and severe sleep deprivation subgroups had significantly higher proportions of children with VIQ-PIQ imbalance than the control group. CONCLUSIONS: Sleep deprivation adversely affects intelligence development, especially VIQ, in primary school students, and the adverse effects of sleep deprivation are mainly seen in students with moderate and severe sleep deprivation.

Abstract:OBJECTIVE: To study the differences in quality of life and psychosocial function between children with short stature and children with normal stature. METHODS: The Pediatric Quality of Life Inventory (PedsQL) was used to survey 53 children aged 5-18 years who were diagnosed with short stature between June 2011 and June 2012, and their parents or guardians. Seventy-nine healthy children aged 4-17 years were selected as the control group. RESULTS: For PedsQL Child-Self Report, the children with short stature had a significantly higher total score than the control children (25.3±11.2 vs 21.1±10.3; P<0.05), and the former had significantly higher scores than the latter on the following items: It is hard for me to walk more than one block; It is hard for me to lift something heavy; I hurt or ache; I worry about what will happen to me; I cannot do things that other kids of my age can do; It is hard to keep up when I play with other kids; It is hard to pay attention in class; I forget things; I have trouble keeping up with my schoolwork (P<0.05). For PedsQL Parent-Proxy Report, the children with short stature had significantly higher scores than the control children on the following items: troubled sleeping; paying attention in class; keeping up with schoolwork; forgetting things (P<0.05). There was no significant difference in total score, however, between the two groups (P>0.05). CONCLUSIONS: Children with short stature have poorer development of psychosocial function than children with normal stature.

Abstract:OBJECTIVE: To study the relationship of serum 25-hydroxyvitamin D [25-(OH)D3] level with obesity and inflammatory cytokines in children, and to provide a basis for clinical evaluation of the relationship between vitamin D nutritional status and obesity. METHODS: Seventy-eight children with obesity who visited the hospital between February and June 2012 were selected as subjects. According to baseline data, such as age and sex, 105 children who underwent physical examination in the same period were selected as controls. Fasting venous blood samples were taken to measure serum levels of 25-(OH)D3, interleukin-6 (IL-6), interleukin-8 (IL-8), interferon-γ (IFN-γ), and tumor necrosis factor α (TNF-α). RESULTS: Serum 25-(OH)D3 levels were significantly lower in the obesity group than in the control group (P<0.01). Serum 25-(OH)D3 levels were negatively correlated with BMI (r=-0.462, P<0.01). Patients were further divided, according to their serum 25-(OH)D levels, into vitamin D sufficiency, vitamin D insufficiency, vitamin D deficiency and severe vitamin D deficiency subgroups. There were significant differences in serum IFN-γ levels among the subgroups (P<0.05). There were no significant differences in serum IL-6, IL-8 and TNF-α levels between the subgroups, however (P>0.05). CONCLUSIONS: Obese children have lower serum 25-(OH)D3 levels than normal children. Serum 25-(OH)D3 level is negatively correlated with BMI, but has little correlation with inflammatory cytokines levels.

Abstract:OBJECTIVE: To investigate nutritional risk and its relationship with clinical outcome in children hospitalized in the surgical department, and to provide a scientific basis for clinical nutrition management. METHODS: Nutritional risk screening was performed on 706 children hospitalized in the surgical department using the Screening Tool for Risk on Nutritional Status and Growth. The data on nutritional support during hospitalization, incidence of infectious complications, length of hospital stay, post operative length of hospital stay and total hospital expenses were recorded. RESULTS: Of the 706 cases, 11.5% had high nutritional risk, 46.0% had moderate nutritional risk, and 42.5% had low nutritional risk. Congenital hypertrophic pyloric stenosis, intestinal obstruction and congenital heart disease were the three most common types of high nutritional risk. The incidence of high nutritional risk was significantly higher in infants than in other age groups (P<0.01). Fifty-two (64.2%) of the eighty-one children with high nutritional risk received parenteral nutrition. Children with high nutritional risk were significantly more likely to have weight loss than children with low nutritional risk (P<0.05). Children with high nutritional risk had significantly increased incidence of infectious complications, length of hospital stay, post operative length of hospital stay and total hospital expenses compared with those with moderate or low nutritional risk (P<0.01). CONCLUSIONS: Moderate or high nutritional risk is seen in children hospitalized in the surgical department. Nutritional risk score is correlated with clinical outcome. Nutritional support for these children is not yet properly provided. Nutritional risk screening and standard nutritional support should be widely applied among hospitalized children.

Abstract:OBECTIVE: To study clinical features, treatment and curative effects in children with acute clenbuterol poisoning, in order to provide a basis for early diagnosis and treatment. METHODS: Clinical data of 28 hospitalized children with acute clenbuterol poisoning in April 2011 were retrospectively studied. RESULTS: Of the 28 patients, there were 15 males and 13 females, aged 1 to 13 years (mean age 6.5±4.8 years). Vomiting, palpitations and limb shaking were found as main clinical manifestations in the patients. Main changes of blood biochemical included hypokalemia, lactic acidosis, hyperglycemia, hypsocreatinkinase. Snus tachycardia and S-T segment depression were observed on ECG. Patients' symptoms were gradually alleviated after 12-78 hours by use of beta blockers, potassium supplement, protecting the heart and other symptomatic and supportive treatment. Blood biochemical indexes were improved after 48 hours of admission. All of the patients were cured after 5 days. The symptoms of the patients do not longer occur during a follow up of half a month. COCLUSIONS: Acute clenbuterol poisoning is characterized by vomiting, palpitations, limb shaking, hypokalemia, lactic acidosis and tachycardia in children. An early effective treatment of this disease can improve prognosis in children.

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OBJECTIVE: To study the effects of erythropoietin (EPO) on cardiomyocyte apoptosis and endoplasmic reticulum stress (ERS)-related proteins, glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP), in neonatal rats with asphyxia. METHODS: A total of 120 newborn Sprague-Dawley rats (7 days old) were randomly divided into sham-operated (n=40), asphyxia (n=40) and EPO-treated asphyxia groups (n=40). A neonatal rat model of normobaric asphyxia was established in the asphyxia and EPO-treated asphyxia groups. The rats in the EPO-treated asphyxia group received intraperitoneal injection of recombinant human erythropoietin (500 U/mL) immediately after the model was established, while the other two groups received the same volume of normal saline (0.9%). Heart blood and myocardial tissue samples were collected from 8 rats in each group at 2, 6, 12, 24 or 48 hours after the model was established. Serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels were measured; cardiomyocyte apoptosis was evaluated, and expression of myocardial GRP78 and CHOP was measured. RESULTS: Compared with the sham-operated and EPO-treated asphyxia groups, the asphyxia group had significantly increased serum CK and LDH levels, number of apoptotic cells, and expression of myocardial GRP78 and CHOP at each time point (P<0.01), and all the indices were significantly higher in the EPO-treated asphyxia group than in the sham-operated group (P<0.01). At 24 hours after asphyxia, the expression of myocardial CHOP was positively correlated with the myocardial apoptosis index (r=0.944, P<0.01). CONCLUSIONS: EPO exerts a protective effect on the myocardium of neonatal rats with hypoxic-ischemic injury by regulating ERS-related proteins GRP78 and CHOP and reducing cardiomyocyte apoptosis.

Abstract:Objective To investigate the role and significance of cardiac mast cells and Toll-like receptor 4 (TLR4) in the development and progression of viral myocarditis (VMC). Methods Forty-eight Balb/c mice were randomly divided into a control group (n=24) and a model group (n=24). Coxsackievirus B3 was intraperitoneally injected into the model group mice to establish a VMC model. In each group, cardiac tissues were collected from 8 mice at 7, 14 and 28 days after the model was established. The cardiac tissues were stained with hematoxylin and eosin as well as Masson trichrome to observe pathological changes in cardiac tissues. The number and degranulation of cardiac mast cells at each time point were measured and evaluated by toluidine blue staining and transmission electron microscopy. The mRNA and protein expression of TLR4 in cardiac tissues was measured by RT-PCR and immunohistochemistry. In the model group, the correlation between number of cardiac mast cells and mRNA expression of TLR4 at all time points was analyzed. Results The model group had significantly higher pathological scores of cardiac tissues than the control group at all time points (P<0.05). The myocardial collagen volume fraction in the model group at 28 days was significantly higher than in the control group at all time points and higher than in the model group at 7 and 14 days (P<0.05). At each time point, the model group had a significantly increased number of mast cells (P<0.05), and significantly increased mRNA and protein expression of TLR4 (P<0.05) compared with the control group. In the model group, the number of cardiac mast cells was positively correlated with the mRNA expression of TLR4 at all time points (R2=0.877, P<0.05). Conclusions Mice with VMC have significantly increased numbers of cardiac mast cells and expression of TLR4 compared with control mice at all time points, suggesting that mast cells and TLR4 may play important roles in the inflammatory response and fibrosis of VMC.

Abstract:OBJECTIVE: To observe the level in plasma hydrogen sulfide (H2S) and the expression of cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE) (two key synthetases for endogenous H2S generation in the kidney) in obstructed kidney tissue among rats with tubulointerstitial fibrosis (TIF) induced by unilateral ureteral obstruction (UUO), and to explore the role of H2S in TIF. METHODS: Ninety-six male Sprague-Dawley rats were randomly divided into sham-operated, model, low-dose NaHS and high-dose NaHS groups (n=24 each). TIF was induced by UUO in the model, low-dose NaHS and high-dose NaHS groups. The low-dose and high-dose NaHS groups were intraperitoneally injected with NaHS (1.4 and 7.0 μmol/kg respectively) twice daily immediately after operation, and the sham-operated and model groups were intraperitoneally injected with an identical volume of normal saline. In each group, 8 rats were randomly selected and sacrificed at 7, 14 or 21 days after operation. Plasma H2S concentration was measured by deproteinization. The obstructed kidney tissue was subjected to hematoxylin and eosin staining and Masson staining, and the renal tubulointerstitial injury was evaluated under a microscope. mRNA and protein expression of CBS and CSE in the obstructed kidney tissue was measured by RT-PCR and immunohistochemistry respectively. RESULTS: The degree of UUO-induced renal tubulointerstitial injury was negatively correlated with plasma H2S concentration in (r=-0.891, P<0.01). With H2S supplementation, renal tubulointerstitial injury was reduced (P<0.01), the expression of mRNA and protein of CBS and CSE in the kidney tissue and plasma H2S level were upregulated (P<0.01), and the degree of TIF was reduced (P<0.01). There were no significant differences in plasma H2S level and mRNA and protein expression of CBS and CSE between the low-dose and high-dose NaHS groups (P>0.05). CONCLUSIONS: H2S is involved in the development of UUO-induced TIF, and the CBS/H2S and CSE/H2S systems play key roles in this process. H2S supplementation can delay the progression of TIF.

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Abstract:Randomized controlled trials have demonstrated the safety and efficacy of mild hypothermia in the treatment of neonatal hypoxic-ischemic encephalopathy (HIE), which can reduce mortality or the incidence of severe neurological sequelae. Mild hypothermia has been used in the neonatal intensive care unit (NICU) as a routine treatment method for neonatal HIE in many developed countries, and it is increasingly applied in some NICUs in China. However, 40%-50% of the neonates treated with mild hypothermia die or develop severe neurological disability. Thus, to achieve the best neuroprotective effect, issues such as selection of patients with indications for mild hypothermia, cooling method, optimal time for mild hypothermia, duration of mild hypothermia, optimal target temperature, and the safety and long-term effects of mild hypothermia combined with other therapies, need to be further discussed. This article reviews the latest progress in clinical research on these issues.