Research Progress on the Prevention of Premature Infant Lung Injury and Neonatal Respiratory Support

In the past 40 years,advances in neonatal intensive care unit(NICU)technology have enabled premature infants with lower birth weight and younger gestational age to survive.But with it comes an increase in the incidence of long-term respiratory dysfunction,mainly in the form of bronchopulmonary dysplasia(BPD).Preventing lung injury is crucial for preventing BPD and improving the long-term prognosis of premature infants.Therefore,how to avoid ventilator-associated lung injury has become a focus of clinical and scientific research in premature infants in recent years.This article will elaborate on the susceptibility and pathophysiology of premature infant lung injury,ventilation strategies for preventing lung injury,and new advances in neonatal respiratory support.

A rabbit model of pediatric nonalcoholic steatohepatitis: The role of adiponectin

AIM： To create a rabbit model of pediatric nonalcoholic steatohepatitis （NASH） and to evaluate the role of adiponectin in the process. METHODS： Thirty-two specific pathogen-free male New Zealand rabbits were divided randomly into three groups： （1） the normal control group （n = 10） was fed with standard diet for 12 wk; （2） the model group A （n = 11）; and （3） model group B （n = 11） were fed with a highfat diet （standard diet ＋ 10% lard ＋ 2% cholesterol） for 8 and 12 wk, respectively. Hepatic histological changes were observed and biochemical parameters as well as serum levels of adiponectin, interleukin （IL）-6, IL-10 and tumor necrosis factor （TNF）-α were measured. RESULTS： Typical histological hepatic lesions of NASH were observed in both model groups described as liver steatosis, liver inflammatory infiltration, cytologic ballooning, perisinusoidal fibrosis and overall fibrosis. Compared with the normal control group, there were significant increases in model groups A and B in weight gain （1097.2 ± 72.3, 1360.5± 107.6 vs 928.0 ±58.1, P 〈 0.05, P 〈 0.01）, liver weight （93.81±6.64, 104.6±4.42 vs 54.4±1.71, P 〈 0.01）, Lg （ALT） （1.9±0.29, 1.84± 0.28 vs 1.60±0.17, P 〈 0.01）, and Lg （TG） （1.03 ±0.24, 1.16 ±0.33 vs 0.00 ±0.16, P 〈 0.01）. Weight gain was much more in model group B than in model group A （1360.5± 107.6 vs 1097.2 ±72.3, P 〈 0.05）. But, there was no significant difference between the two groups concerning the other indexes. Pro-inflammatory cytokines （IL-6 and TNF-α） increased in model group B compared with that of control and model group A （IL-6：1.86±0.21 vs 1.41 ±0.33, 1.38± 0.42, P 〈 0.01; TNF-α： 1.18±0.07 vs 0.66 ±0.08, 0.86 ±0.43, P 〈 0.01, P 〈 0.05）, whereas serum adiponectin and IL-10 decreased in model groups compared with that in the control （adiponectin： A： 21.87±4.84 and B： 21.48 ±4.60 vs 27.36 ±7.29, P 〈 0.05. IL-10： A： 1.72± 0.38 and B： 1.83 ±0.39 vs 2.26±0.24, P 〈 0.01）. Lg （TC） and the degree of liver fatty infiltration was an independent determinant of serum adiponectin level analyzed by stepwise multiple regressions, resulting in 29.4% of variances. CONCLUSION： This rabbit model produces the key features of pediatric NASH and may provide a realistic model for future studies. Adiponectin level partially reflects the severity of liver steatosis, but not the degree of liver inflammation.

Hemolymphangioma: A rare differential diagnosis of cystic-solid or cystic tumors of the pancreas

We report a case of pancreatic hemolymphangioma. Hemolymphangioma is a malformation of both lymphatic vessels and blood vessels. The incidence of this disease in the pancreas is extremely rare. To the best of our knowledge, only seven cases have been reported worldwide (PubMed). A 39-year-old woman with a oneday history of abdominal pain was admitted to our hospital. There was no obvious precipitating factor. The preoperative examination, including ultrasonography and computed tomography, showed a cystic-solid tumor in the pancreas, and it was considered to be a mucinous cystadenoma or cystadenocarcinoma. Pancreaticbody-tail resection combined with splenectomy was performed. After the operation, the tumor was pathologically demonstrated to be a pancreatic hemolymphangioma. Although pancreatic hemolymphangioma is rare, we believe that it should be considered in the differential diagnosis of cystic-solid tumors of the pancreas, particularly when there is no sufficient evidence for diagnosing cystadenoma, cystadenocarcinoma or some other relatively common disease of the pancreas.

Therapeutic upper gastrointestinal tract endoscopy in Paediatric Gastroenterology

Since the first report of use of endoscopy in children in the 1970 s, there has seen an exponential growthin published experience and innovation in the field. In this review article we focus on modern age therapeutic endoscopy practice, explaining use of traditional as well as new and innovative techniques, for diagnosis and treatment of diseases in the paediatric upper gastrointestinal tract.

Ketamine induces tau hyperphosphorylation at serine 404 in the hippocampus of neonatal rats

Male Wistar 7-day-old rats were injected with 40 mg/kg ketamine intraperitoneally, followed by three additional injections of 20 mg/kg ketamine each upon restoration of the righting reflex. Neonatal rats injected with equivalent volumes of saline served as controls. Hippocampal samples were collected at 1,7 or 14 days following administration. Electron microscopy showed that neuronal structure changed noticeably following ketamine treatment. Specifically, microtubular structure became irregular and disorganized. Quantitative real time-PCR revealed that phosphorylated tau mRNA was upregulated after ketamine. Western blot analysis demonstrated that phosphorylated tau levels at serine 396 initially decreased at 1 day after ketamine injection, and then gradually returned to control values. At 14 days after injection, levels of phosphorylated tau were higher in the ketamine group than in the control group. Tau protein phosphorylated at serine 404 significantly increased after ketamine injection and then gradually decreased with time. However, the levels of tau protein at serine 404 were significantly greater in the ketamine group than in the control group until 14 days. The present results indicate that ketamine induces an increase of phosphorylated tau mRNA and excessive phosphorylation of tau protein at serine 404, causing disruption of microtubules in the neonatal rat hippocampus and potentially resulting in damage to hippocampal neurons.

History of the infantile hepatic hemangioma:From imaging to generating a differential diagnosis

We aim to provide an up-to-date summary of infantile hepatic hemangioma(IHH) and its misnomers and to dialectically present the differential diagnosis of these rare entities of the liver.Eligible peer-reviewed articles on hepatic infantile hemangiomas,published between 2000 and 2015,were reviewed for this study.IHH is the most common hepatic vascular tumor in children.Once a liver mass is identified in an infant,the differential diagnosis ranges from vascular malformations to benign and malignant tumors including mesenchymal hamartoma,hepatoblastoma,metastatic neuroblastoma,so careful physical examination,imaging studies,and,if indicated,tumor markers and biopsy,are of pivotal importance to ascertain the correct diagnosis.Despite the benign nature of IHHs,some of these lesions may demand medical and/or surgical intervention,especially for multiple and diffuse IHH.Complications can include hepatomegaly,hypothyroidism and cardiac failure.Therefore,a close follow-up is required until complete involution of the lesions.We propose an algorithm to guide the physicians towards the proper management of hepatic lesions.

Australian Hajj pilgrims' knowledge about MERS-CoV and other respiratory infections

Dear Editor,With the intense crowding in mass gatherings such as Hajj,there is a high risk of acquisition of airborne in-fections with the potential for its transmission in the pilgrims’country of origin(Memish Z A,et al.,2014).The risk of importing serious infections from Hajj has escalated since the emergence of the Middle East respiratory syndrome coronavirus(MERS-CoV)in Saudi Arabia and other neighbouring countries from September2012.Active surveillance of Hajj pilgrims in 2012 and 2013

Increasing the dosage of vincristine: a clinical and pharmacokinetic study of continuous-infusion vincristine in children with central nervous system tumors

BACKGROUND: Vincristine (VCR) is widely used to treat patients with malignant disease; among the patients treated with VCR are children with brain tumors. In vitro studies have demonstrated that the cytotoxic activity of VCR is related to both extracellular concentration and duration of exposure. The attainment of higher plasma concentrations by injecting larger bolus doses of VCR has been limited by concerns about neurotoxicity. One possible alternative strategy for enhancing the antitumor efficacy of VCR involves prolonging the duration of in vivo exposure. Therefore, the authors explored the neurotoxicity and pharmacokinetics of VCR administered via a 96hour continuous infusion after administration of a conventional bolus dose in a pediatric population. METHODS: The current study included 16 patients, 11 of whom were males. The median age of the study population was 4. 8 years (range, 1.7-15. 8 years).

CHOP THER APY INDUCED MITOCHONDRIAL REDOX STATE ALTERATION IN NON-HODGKIN'S LYMPHOMA XENOGRAFTS

We are interested in investigating whether cancer therapy may alter the mitochondrial redox state in cancer cells to inhibit their growth and survival.The redox state can be imaged by the redox scanner that collects the fuorescence signals from both the oxidized-fAavoproteins(Fp)and the reduced form of nicotinamide adenine dinucleotide(NADH)in snap frozen tissues and has been previously employed to study tumor aggressiveness and treatment responses.Here,with the redox scanner we investigated the effects of chemotherapy on mouse xenografts of a human diffuse large B.cell lymphoma cell line(DLCL2).The mice were treated with CHOP therapy,i.e,cyclophosphamide(C)+hydroxydoxorubicin(H)+Oncovin(O)+prednisone(P)with CHO administration on day 1 and prednisone administration on days 1-5.The Fp content of the treated group was significantly decreased(p=0.033)on day 5,and the mitochondrial redox state of the treated group was slightly more reduced than that of the control group(p=0.048).The decrease of the Fp heterogeneity(measured by the mean st andard deviation)had a border-line statistical significance(p=0.071).The result suggests that the mitochondrial metabolism of lymphoma cells was slightly suppressed and the lymphomas became less aggressive after the CHOP therapy.

Listeria monocytogenes meningitis in three immunocompetent children and a review of the literature

Objective:To summarize the clinical characteristics and treatment outcome of 3 cases of Listeria monocytogenes(Lm)meningitis in immunocompetent children,improve clinicians'awareness of the disease.Methods:The clinical features and treatment of Lm meningitis in children admitted to Children's Hospital of Zhejiang University School of Medicine from January 2016 to May 2019 were analyzed retrospectively.We summarized related literatures,and compared the selection of antibiotics in children with Lm meningitis reported in cases.Results:All patients had fever,vomiting and other symptoms,CSF as purulent meningitis performance,Ampicillin is currently the first choice of treatment,while meropenem and Linezolid could be administered as alternative drugs for Lm meningitis.Conclusions:For children with meningitis,when the empirical antibiotics treatment fill,the possibility of Lm meningitis should be considered,and antibiotics that can effectively cover Lm should be adjusted in time.

Association between the polymorphisms of the VDR gene and kidney stone formation in Guangxi population

Objective:To investigate the relationship between the rs9729,rs11574129,BsmI(rs1544410),TaqI(rs731236)and DdeI(rs3782905)polymorphisms of the vitamin D receptor(VDR)gene and kidney stone formation in a study group from Guangxi.Methods:A hospital-based casecontrol study including 890patients with kidney stone formation and 822age-and sex-matched controls without stone formation was conducted.Five single-nucleotide polymorphisms(SNPs)of the VDR gene were studied using SNPscanTMhighthroughput SNP classification assays.Results:The T allele variant of rs9729significantly increased the risk of kidney stone formation(P=0.021).In particular,a significantly increased risk of kidney stone formation was found in the combined genotypes TG/TT of rs9729compared with the wild GG genotype after covariate adjustment.However,after gender stratification analysis,compared with the wild GG genotype,the GT,TT and GT/TT genotypes of rs9729increased the risk of kidney stone formation in males.Moreover,the GA and GA/GG genotypes of rs11574129 were associated with increased risk of kidney stone formation in males.By contrast,the GC and GC/CC genotypes of DdeI(rs3782905)significantly decreased the risk of kidney stone formation in males.Haplotype analysis suggested that the five-locus polymorphism of VDR was significantly related to kidney stone formation in male participants(P=0.0025).Conclusion:TheT allele variant of the rs9729polymorphism of the VDR gene was significantly related to the risk of kidney stone formation.Gender may affect the association between the rs9729,rs11574129and DdeI polymorphisms of the VDR gene and the risk of kidney stone formation in the Chinese population.

Efficacy of Azithromycin sequential therapy combined with Tanreqing injection for treatment of children with mycoplasma pneumonia

Objective:To study the effect of Azithromycin sequential therapy combined with Tanreqing injection on serum sTREM-1, CK, G-CSF, IL-10, CRP and TNF-α in children with mycoplasma pneumonia.Methods:A total of 80 children with mycoplasma pneumonia in our hospital from June 2014 to September 2016 were enrolled in this study. The subjects were divided into the control group (n=40) and the treatment group (n=40) randomly. The control group were treated with Azithromycin sequential therapy, the treatment group were treated with Azithromycin sequential therapy combined with Tanreqing injection. The two groups were treated for 2 periods. The serum sTREM-1, CK, G-CSF, IL-10, CRP and TNF-α levels of the two groups before and after treatment were compared.Results: There were no significantly differences of the serum sTREM-1, CK, G-CSF, IL-10, CRP and TNF-α levels of the two groups before treatment. The serum sTREM-1, CK, G-CSF, IL-10, CRP and TNF-α levels of the two groups after treatment were significantly lower than before treatment, and that of the treatment group were significantly lower than the control group.Conclusion:Azithromycin sequential therapy combined with Tanreqing injection can significantly reduce the serum sTREM-1, CK, G-CSF, IL-10, CRP and TNF-α levels of children with mycoplasma pneumonia, have good clinical efficacy, and it was worthy clinical application.

Effect of nutrition-related infodemics and social media on maternal experience: A nationwide survey in a low/middle income country

BACKGROUND Undernutrition is a crucial cause of morbidity and mortality among children in low-or middle-income countries(LMICs).A better understanding of maternal general healthy nutrition knowledge,as well as misbeliefs,is highly essential,especially in such settings.In the current era of infodemics,it is very strenuous for mothers to select not only the right source for maternal nutrition information but the correct information as well.AIM To assess maternal healthy nutritional knowledge and nutrition-related misbeliefs and misinformation in an LMIC,and to determine the sources of such information and their assessment methods.METHODS This cross-sectional analytical observational study enrolled 5148 randomly selected Egyptian mothers who had one or more children less than 15 years old.The data were collected through online questionnaire forms:One was for the general nutrition knowledge assessment,and the other was for the nutritional myth score.Sources of information and ways of evaluating internet sources using the Currency,Relevance,Authority,Accuracy,and Purpose test were additionally analyzed.RESULTS The mean general nutrition knowledge score was 29±9,with a percent score of 70.8%±12.1%(total score:41).The median myth score was 9(interquartile range:6,12;total score:18).The primary sources of nutrition knowledge for the enrolled mothers were social media platforms(55%).Half of the mothers managed information for currency and authority,except for considering the author's contact information.More than 60%regularly checked information for accuracy and purpose.The mothers with significant nutrition knowledge checked periodically for the author's contact information(P=0.012).The nutrition myth score was significantly lower among mothers who periodically checked the evidence of the information(P=0.016).Mothers dependent on their healthcare providers as the primary source of their general nutritional knowledge were less likely to hold myths by 13%(P=0.044).However,using social media increased the likelihood of having myths among mothers by approximately 1.2(P=0.001).CONCLUSION Social media platforms were found to be the primary source of maternal nutrition information in the current era of infodemics.However,healthcare providers were the only source for decreasing the incidence of maternal myths among the surveyed mothers.

对儿童用药和临床试验的思考

近年来,有高达79%的儿科药物在没有明确标识或者没有额外获得儿童使用许可的情况下使用[1]。2006年,我国医院对于4亿儿科患者使用的1 103种药品中仅有64种（占5.8%）是按说明书指导使用的[2]。另有数据显示,中国患病儿童占总患病人口的20%左右,但80%以上的已上市药品没有儿童使用标识,90%的药物没有儿童剂型[3]。

定量药理学:一个促进药物开发及转换型研究严谨思考的多学科领域

尽管从事定量药理学研究的科学工作者一再强调将定量分析的原则应用于促进新药研发的决策,定量药理学的发展还是超过了上述领域。普通研究和决策领域总是期望着常规和传统的研究范例发生进步,当与定量药理学相关的领域自身在发展并与其交互作用时,自然便产生对临床药理学的协同作用。创新性和可塑性训练计划和策略均是将来临床研究工作中必不可少的要素。掌握定量药理学领域的知识成为对药理科学家的要求,具有定量药理学背景的人员可望获得更高的薪水。目前定量药理学相关培训计划,教学资料,及学术权威均比较贫乏,学生们可以从企业化、调控性的背景的教师等多种机构的教职员那获得指导,此外也可以通过在线课程,可视化教学进修课程,与他们的导师保持联系。对课程和学位的管理可以采取灵活的态度,这样可在短期内培养更多的定量药理学工作者。

Effect of lifestyle intervention on non-alcoholic fatty liver disease in Chinese obese children

AIM: To investigate the effect of lifestyle intervention on non-alcoholic fatty liver disease (NAFLD) in Chinese obese children. METHODS: Seventy-six obese children aged from 10 to 17 years with NAFLD were enrolled for a one-month intervention and divided randomly into three groups. Group1, consisting of 38 obese children, was an untreated control group without any intervention. Group 2, consisting of 19 obese children in summer camp, was strictly controlled only by life style intervention. Group 3, consisting of 19 obese children, received oral vitamin E therapy at a dose of 100 mg/d. The height, weight, fasting blood glucose (FBG), fasting serum insulin (FINS), plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TCHO) and homeostasis model assent- insulin resistance (HOMA-IR) were measured at baseline and after one month. All patients were underwent to an ultrasonographic study of the liver performed by one operator who was blinded to the groups. RESULTS: The monitor indices of BMI, ALT, AST, TG, TCHO and HOMA-IR were successfully improved except in group 1. BMI and ALT in group 2 were reduced more significantly than in group 3 (2.44 ± 0.82 vs 1.45 ± 0.80, P = 0.001; 88.58 ± 39.99 vs 63.69 ± 27.05, P = 0.040, respectively).CONCLUSION: Both a short-term lifestyle intervention and vitamin E therapy have an effect on NAFLD in obese children. Compared with vitamin E, lifestyle intervention is more effective. Therefore, lifestyle intervention should represent the first step in the management of children with NAFLD.

定量药理学与儿童药物研发和合理用药

This article provides a comprehensive overview of key issues related to pediatric drug development and rational dosing guidance in pediatrics with an emphasis on how pharmacometrics can improve the efficiency and productivity of pediatric trials.The pharmacokinetics(PK)and pharmacodynamics(PD)of drugs are often different between adult and pediatric populations which necessitate specific studies in children.The aims of this review are to discuss a number of recent methodological developments of modeling and simulation that facilitate the evaluation of drugs in pediatrics.Specific focus has been placed on addressing the key issues of PK/PD scaling,sparse sampling,colinearity,covariate evaluation,dose optimization for trial design and label,modeling strategies and validation approaches.The features and potential advantages of Bayesian hierarchical model,physiology-based PK models,and K-PD models are also presented.

Mitochondrial DNA mutations associated with aminoglycoside induced ototoxicity

Aminoglycosides(Am An) are widely used for their great efficiency against gram-negative bacterial infections. However, they can also induce ototoxic hearing loss, which has affected millions of people around the world. As previously reported, individuals bearing mitochondrial DNA mutations in the 12 S rRNA gene, such as m.1555A>G and m.1494C>T, are more prone to Am An-induced ototoxicity. These mutations cause human mitochondrial ribosomes to more closely resemble bacterial ribosomes and enable a stronger aminoglycoside interaction. Consequently,exposure to Am An can induce or worsen hearing loss in these individuals. Furthermore, a wide range of severity and penetrance of hearing loss was observed among families carrying these mutations. Studies have revealed that these mitochondria mutations are the primary molecular mechanism of genetic susceptibility to Am An ototoxicity, though nuclear modifier genes and mitochondrial haplotypes are known to modulate the phenotypic manifestation.

Non-alcoholic fatty liver disease:An early mediator predicting metabolic syndrome in obese children?

AIM:To investigate if non-alcoholic fatty liver disease (NAFLD) is an early mediator for prediction of metabolic syndrome,and if liver B-ultrasound can be used for its diagnosis.METHODS:We classified 861 obese children (6-16 years old) into three subgroups:group 0 (normal liver in ultrasound and normal transaminases);group 1 (fatty liver in ultrasound and normal transaminases);and group 2 (fatty liver in ultrasound and elevated transaminases).We measured the body mass index,waist and hip circumference,blood pressure,fasting blood glucose,insulin,homeostasis model assessment of insulin resistance (HOMA-IR),whole-body insulin sensitivity index (WBISI),lipid profile and transaminases in all the participants.The risk of developing metabolic syndrome (MS) was assessed according to the degree of liver fatty infiltration based on the B-ultrasound examination.RESULTS:Among the 861 obese children,587 (68.18%) were classified as having NAFLD,and 221 (25.67%) as having MS.The prevalence of MS in NAFLD children (groups 1 and 2) was 37.64% (221/587),which was much higher than that in non-NAFLD group (group 0,12.04%) (P < 0.01).There were significantly higher incidences concerning every component of MS in group 2 compared with group 0 (P < 0.05).The incidence of NAFLD in MS patients was 84.61% (187/221),which was significantly higher than that of hypertension (57.46%,127/221) and glucose metabolic anomalies (22.62%,50/221),and almost equal to the prevalence of dyslipidemia (89.14%,197/221).Based on the B-ultrasound scales,the presence of moderate and severe liver fatty infiltration carried a high risk of hypertension [odds ratio (OR):2.18,95% confidence interval (95% CI):1.27-3.75],dyslipidemia (OR:7.99,95% CI:4.34-14.73),impaired fasting glucose (OR:3.65,95% CI:1.04-12.85),and whole MS (OR:3.77;95% CI:1.90-7.47,P < 0.01).The state of insulin resistance (calculated by HOMA-IR and WBISI) deteriorated as the degree of fatty infiltration increased.CONCLUSION:NAFLD is not only a liver disease,but also an early mediator that reflects metabolic disorder,and liver B-ultrasound can be a useful tool for MS screening.

Single-center experience of 309 consecutive patients with obscure gastrointestinal bleeding

AIM: To investigate the diagnostic yield of capsule endoscopy (CE) in patients with obscure gastrointestinal bleeding (OGIB), and to determine whether the yield was affected by different bleeding status. METHODS: Three hundred and nine consecutive patients (all with recent negative gastric and colonic endoscopy results) were investigated with CE; 49 cases with massive bleeding and 260 cases with chronic recurrent overt bleeding. Data regarding OGIB were obtained by retrospective chart review and review of an internal database of CE fi ndings.RESULTS: Visualization of the entire small intestine was achieved in 81.88% (253/309) of cases. Clinically positive findings occurred in 53.72% (166/309) of cases. The positivity of the massive bleeding group was slightly higher than that of the chronic recurrent overt bleeding group but there was no significant difference (59.18% vs 52.69%, P > 0.05) between the two groups. Small intestinal tumors were the most common fi nding in the entire cohort, these accounted for 30% of clinically signifi cant lesions. In the chronic recurrent overt bleeding group angioectasia incidence reached more than 29%, while in the massive bleedinggroup, small intestinal tumors were the most common finding at an incidence of over 51%. Increasing patient age was associated with positive diagnostic yield of CE and the findings of OGIB were different according to age range. Four cases were compromised due to the capsule remaining in the stomach during the entire test, and another patient underwent emergency surgery for massive bleeding. Therefore, the complication rate was 1.3%. CONCLUSION: In this study CE was proven to be a safe, comfortable, and effective procedure, with a high rate of accuracy for diagnosing OGIB.