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.

Clinical Engineering Benchmarking Comparison Between Zhejiang Province and American Hospitals

Clinical engineering(CE) has evolved rapidly over the last 25 years in China. Among the 34 provincial-level administrative units within China, the Zhejiang Province is one of the most advanced in terms of healthcare technology maintenance and management. In order to determine Zhejiang's current stage of development and opportunities for further improvement, a comparison of the performance of its CE departments was made against hospitals in the USA. Data were collected from 21 Zhejiang hospitals and compared to those from 270 acute-care hospitals in USA collected by Truven Health Analytics. The benchmarking comparison was made in three categories: operational, financial, and productivity. Within the operational category, the following metrics were compared: equipment inventory size/operating beds, annual repairs/inventory size, and annual scheduled maintenance/inventory size. Within the Financial category, the following metrics were compared: total CE expense/operating beds and total CE expense/total hospital expense. Within the Productivity category, the following metrics were compared: total CE full-time equivalent(FTE)/inventory size and total CE FTE/total hospital expense. These comparisons showed that:(1) While the equipment inventory in Zhejiang tends to be much smaller than USA for hospitals of comparable amount of operating beds, the numbers of repairs and scheduled maintenance per inventory size are similar;(2) The total CE expense/total hospital expense ratio is around 1% in both Zhejiang and USA; however, the total CE expense/operating beds and total CE expense/cost of equipment inventory are significantly lower in Zhejiang than USA;(3) The FTE amount in Zhejiang is significantly higher than in USA relative to both inventory size and total hospital operating expense, but significantly lower relative to the number of operating beds. The fact that repairs and scheduled maintenance are similar in Zhejiang and USA shows that CE leaders are managing equipment in comparable manner. Most of the differences found in the comparisons were traced to a few factors. First, the average length of stay in China is substantially higher than USA, which explains why hospitals in Zhejiang tend to have more operating beds but fewer pieces of equipment. Second, labor cost is significantly lower in China than USA, thus allowing Zhejiang hospitals to employ more workers than their American counterparts. Third, there is significantly difference in the cost of living between China and USA; Finally, being public entities Chinese hospitals are managed and operated in a different manner than American hospitals, which are mostly private, albeit nonprofit organizations. Nonetheless, it is interesting to note that hospitals in both areas spend roughly 1% of their total expenditure for CE. The results suggest that CE in Zhejiang is comparable to USA in terms of managerial excellence but there could be some room for improvement in financial management and productivity.

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.

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.

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 specif ic 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 signif icant 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.

Factors associated with fasting plasma ghrelin levels in children and adolescents

AIM:To measure plasma ghrelin levels in children and adolescents, analyze the associated factors, and investigate the role of ghrelin in obesity, insulin resistance and reproductive physiology. METHODS:A total of 283 subjects aged 4.8-15.8 year were enrolled. Fasting blood samples were collected and plasma ghrelin levels were measured by radioimmunoassay. Fasting glucose (FG), fasting insulin (FI), baseline testosterone (T), estradiol (E2), prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), serum total cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT) and uric acid (UA) were measured. Body mass index (BMI), insulin resistance by homeostasis model (HOMA-IR) and beta cell function by homeostasis model (HOMA-β) were calculated. RESULTS:The median ghrelin level was 290 ng/L (15.0-1325.0 ng/L). Bivariate correlation analysis showed that ghrelin levels were inversely correlated with BMI, ALT, TG, UA, LH, FI and HOMA-IR (all P < 0.05). No other significant correlation was found between ghrelin levels and age, gender, TC, E2, FSH, PRL, FG and HOMA-β. Stepwise multiple regression analysis showed that only BMI and FI were independent determinants of plasma ghrelin levels in these children and adolescents (P = 0.018 and P = 0.046, respectively), which explained 25.4% of the variance. CONCLUSION:These data suggest that the lower ghrelin levels in obese subjects may be the result of obesity and hyperinsulinemia, which is very common in obese subjects. Moreover, ghrelin may regulate human reproductive physiology indirectly.

CagA^+ H.pylori Induces Akt1 Phosphorylation and Inhibits Transcription of p21^(WAF1/CIP1) and p27^(KIP1) via PI3K/Akt1 Pathway

Objective Cytotoxin-associated protein （CagA） of H. pylori has been confirmed to be closely associated with gastric inflammation and tumorigenesis, but the mechanism behind it is little understood. In this study, we try to determine roles of CagA＋ strain in activating PI3K/Akt1 signaling pathway, and affecting expression of p21WAF1/CIP1 and p27KIP1, and also in releasing IL-8 in host cells. Methods Akt1 phosphorylation and IL-8 levels of CagA＋ and CagAˉ strain infected AGS cells were detected by ELISAs. Two quantitative RT-PCRs were established to measure p21WAF1/CIP1 and p27KIP1 mRNA levels in the CagA＋ and CagAˉ strain infected cells. LY294002, an inhibitor of PI3K/Akt pathway, was used to define effect of the pathway in IL-8 release. Results CagA＋ strain could induce an obvious elevation of Akt1 phosphorylation in the infected AGS cells while CagAˉ strain failed to do so. The CagA＋ H. pylori strain infected AGS cells showed significant drops both in p21WAF1/CIP1 and p27KIP1 mRNA levels, whereas the CagAˉ H. pylori strain caused a remarkable increase in p21WAF1/CIP1 mRNA without affecting p27KIP1 gene transcription in the AGS cells. Both the CagA＋ and CagAˉ H. pylori strains enabled AGS cells to produce close elevated levels of IL-8, and the LY294002 block resulted in unexpected elevations of IL-8 levels. Conclusion CagA can activate PI3K/Akt1 pathway that plays an inhibitory role in IL-8 release in H. pylori infected AGS cells. Activation of PI3K/Akt1 pathway and subsequent negative regulation of p21^WAF1/CIP1 and p27^KIP1 expression might be involved in CagA-associated carcinogenesis.

Enhanced recovery after surgery strategy to shorten perioperative fasting in children undergoing non-gastrointestinal surgery:A prospective study

BACKGROUND Enhanced recovery after surgery strategies are increasingly implemented to improve the management of surgical patients.AIM To evaluate the effects of new perioperative fasting protocols in children≥3 mo of age undergoing non-gastrointestinal surgery.METHODS This prospective pilot study included children≥3 mo of age undergoing nongastrointestinal surgery at the Children’s Hospital(Zhejiang University School of Medicine)from January 2020 to June 2020.The children were divided into either a conventional group or an ERAS group according to whether they had been enrolled before or after the implementation of the new perioperative fasting strategy.The children in the conventional group were fasted using conventional strategies,while those in the ERAS group were given individualized fasting protocols preoperatively(6-h fasting for infant formula/non-human milk/solids,4-h fasting for breast milk,and clear fluids allowed within 2 h of surgery)and postoperatively(food permitted from 1 h after surgery).Pre-operative and postoperative fasting times,pre-operative blood glucose,the incidence of postoperative thirst and hunger,the incidence of perioperative vomiting and aspiration,and the degree of satisfaction were evaluated.RESULTS The study included 303 patients(151 in the conventional group and 152 in the ERAS group).Compared with the conventional group,the ERAS group had a shorter pre-operative food fasting time[11.92(4.00,19.33)vs 13.00(6.00,20.28)h,P<0.001],shorter preoperative liquid fasting time[3.00(2.00,7.50)vs 12.00(3.00,20.28)h,P<0.001],higher preoperative blood glucose level[5.6(4.2,8.2)vs 5.1(4.0,7.4)mmol/L,P<0.001],lower incidence of thirst(74.5%vs 15.3%,P<0.001),shorter time to postoperative feeding[1.17(0.33,6.83)vs 6.00(5.40,9.20),P<0.001],and greater satisfaction[7(0,10)vs 8(5,10),P<0.001].No children experienced perioperative aspiration.The incidences of hunger,perioperative vomiting,and fever were not significantly different between the two groups.CONCLUSION Optimizing fasting and clear fluid drinking before non-gastrointestinal surgery in children≥3 mo of age is possible.It is safe and feasible to start early eating after evaluating the recovery from anesthesia and the swallowing function.

U-Net-based deep learning for tracking and quantitative analysis of intracellular vesicles in time-lapse microscopy images

Fluorescence microscopy has become an essential tool for biologists,to visualize the dynamics of intracellular structures with specific labeling.Quantitatively measuring the dynamics of moving objects inside the cell is pivotal for understanding of the underlying regulatory mechanism.Protein-containing vesicles are involved in various biological processes such as material transportation,organelle interaction,and hormonal regulation,whose dynamic characteristics are signi¯cant to disease diagnosis and drug screening.Although some algorithms have been developed for vesicle tracking,most of them have limited performance when dealing with images with low resolution,poor signal-to-noise ratio(SNR)and complicated motion.Here,we proposed a novel deep learning-based method for intracellular vesicle tracking.We trained the U-Net for vesicle localization and motion classification,with demonstrates great performance in both simulated datasets and real biological samples.By combination with fan-shaped tracker(FsT)we have previously developed,this hybrid new algorithm significantly improved the performance of particle tracking with the function of subsequently automated vesicle motion classification.Furthermore,its performance was further demonstrated in analyzing with vesicle dynamics in different temperature,which achieved reasonable outcomes.Thus,we anticipate that this novel method would have vast applications in analyzing the vesicle dynamics in living cells.

A Multicenter Study of Viral Aetiology of Community-Acquired Pneumonia in Hospitalized Children in Chinese Mainland

Community-acquired pneumonia(CAP) is one of the leading causes of morbidity and mortality in children worldwide.In this study,we aimed to describe the aetiology of viral infection of pediatric CAP in Chinese mainland.During November2014 to June 2016,the prospective study was conducted in 13 hospitals.The hospitalized children under 18 years old who met the criteria for CAP were enrolled.The throat swabs or nasopharyngeal aspirates(NPAs) were collected which were then screened 18 respiratory viruses using multiplex PCR assay.Viral pathogens were present in 56.6%(1539/2721) of the enrolled cases,with the detection rate of single virus in 39.8% of the cases and multiple viruses in 16.8% of the cases.The most frequently detected virus was respiratory syncytial virus(RSV)(15.2%,414/2721).The highest detection rate of virus was in <6-month-age group(70.7%,292/413).RSV,human metapneumovirus(HMPV),human parainfluenza viruses(HPIVs) and influenza B virus(Flu B) showed the similar prevalence patterns both in north and south China,but HPIVs,Flu A,human bocavirus(HBoV),human adenovirus(HAdV) and human coronaviruses(HCoVs) showed the distinct circulating patterns in north and south China.Human enterovirus/human rhinovirus(HEV/HRV)(27.6%,27/98),HBoV(18.4%,18/98),RSV(16.3%,16/98) and HMPV(14.3%,14/98) were the most commonly detected viruses in severe pneumonia cases with single virus infection.In conclusion,viral pathogens are frequently detected in pediatric CAP cases and may therefore play a vital role in the aetiology of CAP.RSV was the most important virus in hospitalized children with CAP in Chinese mainland.

Xuefuzhuyu decoction and astragalus prevent hypoxic-ischemic brain injury

Hypoxic-ischemic brain injury models were generated by bilateral carotid artery ligation in Sprague-Dawley rats. Successful models were treated with a combination of Xuefuzhuyu decoction and 10g of astragalus. The experimental results showed that neuronal morphology and structure recovered, nerve growth factor mRNA expression increased in brain tissues, and neurological function signifi-cantly improved. There was no significant difference in these measures compared with rats treated with Xuefuzhuyu decoction alone or a combined treatment of Xuefuzhuyu decoction with 40 g as-tragalus. These experimental findings revealed that, Xuefuzhuyu decoction combined with astra-galus may up-regulate the expression of nerve growth factor mRNA and accordingly exert a neu-roprotective effect; however, this protection is not dependent on astragalus dosage.

Outcomes of two-stage double-level rotational osteotomy in treating patients with congenital proximal radioulnar synostosis

Congenital proximal radioulnar synostosis(CPRUS)is a rare anomaly which is caused by abnormal fusion of the proximal radius and ulna during development.This is due to the failure of embryological separation,resulting in the fixed position of the forearm,from mild to severe pronation.1Mild deformity leads to slight disability because the shoulder and wrist can effectively compensate.2 Patients with bilateral cases and/or pronation defor-mity of>60°may be severely limited in daily activities.34 Most surgeons recommend surgical intervention when the loss of forearm rotation exceeds 60°,particularly when the forearm is fixed in pronation.

Novel function of biguanides in inhibition of phospholipase D1 expression via a translational mechanism in cancer cells

Phospholipase D(PLD)and its product phosphatidic acid(PA)function as pleiotropic factors in the regulation of cancer progression,which includes the promotion of cell growth,survival,cell migration,and angiogenesis.1 Chemical inhibition of the enzymatic activity of PLD1 and PLD2,or genetic down-regulation of their expression both induce tumor suppression,1 while the compounds for PLD expression inhibition are barely reported.Here,we astonishingly found that the anti-hyperglycemic agents biguanides decreased PLD1 protein expression in cancer cells and further investigated its underlying regulatory mechanism.

A multi-center study on Molecular Epidemiology of Human Respiratory Syncytial Virus from Children with Acute Lower Respiratory Tract Infections in the Mainland of China between 2015 and 2019

Human respiratory syncytial virus(RSV) is a major pathogen of acute lower respiratory tract infection among young children. To investigate the prevalence and genetic characteristics of RSV in China, we performed a molecular epidemiological study during 2015–2019. A total of 964 RSV-positive specimens were identified from 5529 enrolled patients during a multi-center study. RSV subgroup A(RSV-A) was the predominant subgroup during this research period except in2016. Totally, 535 sequences of the second hypervariable region(HVR-2) of the G gene were obtained. Combined with182 Chinese sequences from GenBank, phylogenetic trees showed that 521 RSV-A sequences fell in genotypes ON1(512),NA1(6) and GA5(3), respectively;while 196 RSV-B sequences fell in BA9(193) and SAB4(3). ON1 and BA9 were the only genotypes after December 2015. Genotypes ON1 and BA9 can be separated into 10 and 7 lineages, respectively. The HVR-2 of genotype ON1 had six amino acid changes with a frequency more than 10%, while two substitutions H258 Q and H266 L were co-occurrences. The HVR-2 of genotype BA9 had nine amino acid substitutions with a frequency more than10%, while the sequences with T290 I and T312 I were all from 2018 to 2019. One N-glycosylation site at 237 was identified among ON1 sequences, while two N-glycosylation sites(296 and 310) were identified in the 60-nucleotide duplication region of BA9. To conclusion, ON1 and BA9 were the predominant genotypes in China during 2015–2019. For the genotypes ON1 and BA9, the G gene exhibited relatively high diversity and evolved continuously.

Epidemiology of respiratory distress and the illness severity in late preterm or term infants： a prospective multi-center study

Background The severity of respiratory distress was associated with neonatal prognosis. This study aimed to explore the clinical characteristics, therapeutic interventions and short-term outcomes of late preterm or term infants who required respiratory support, and compare the usage of different illness severity assessment tools.Methods Seven neonatal intensive care units in tertiary hospitals were recruited. From November 2008 to October 2009, neonates born at ≥34 weeks＇ gestational age, admitted at 〈72 hours of age, requiring continuous positive airway pressure （CPAP） or mechanical ventilation for respiratory support were enrolled. Clinical data including demographic variables, underlying disease, complications, therapeutic interventions and short-term outcomes were collected. All infants were divided into three groups by Acute care of at-risk newborns （ACoRN） Respiratory Score 〈5, 5-8, and 〉8.Results During the study period, 503 newborn late preterm or term infants required respiratory support. The mean gestational age was （36.8±2.2） weeks, mean birth weight was （2734.5±603.5） g. The majority of the neonates were male （69.4%）, late preterm （63.3%）, delivered by cesarean section （74.8%）, admitted in the first day of life （89.3%） and outborn （born at other hospitals, 76.9%）. Of the cesarean section, 51.1% were performed electively. Infants in the severe group were more mature, had the highest rate of elective cesarean section, Apgar score 〈7 at 5 minutes and resuscitated with intubation, the in-hospital mortality increased significantly. In total, 58.1% of the patients were supported with mechanical ventilation and 17.3% received high frequency oscillation. Adjunctive therapies were commonly needed.Higher rate of infants in severe group needed mechanical ventilation or high frequency oscillation, volume expansion,bicarbonate infusion or vasopressors therapy （P 〈0.05）. The incidence of complications was also increased significantly in severe group （P 〈0.05）. The in-hospital mortality in the severe group was significantly higher than other two groups （P〈0.05）. ACoRN Respiratory Score was correlated with Score for Neonatal Acute Physiology-Version Ⅱ （SNAP-Ⅱ） （P〈0.01）. High gestational age, high SNAP-Ⅱ score and oxygenation index （OI）, and Apgar score at 5 minutes 〈5 were independent risks for death.Conclusions Neonatal respiratory distress is still a common cause of hospitalization in China. Illness severity assessment is important for the management. ACoRN Respiratory Score which correlated with SNAP-Ⅱ score is easy to use and may be helpful in facilitating the caregivers in local hospital to identify the early signs and make the transfer decision promptly.

The etiology of congenital nephrotic syndrome: current status and challenges

Background:Congenital nephrotic syndrome(CNS),defined as heavy proteinuria,hypoalbuminemia,hyperlipidemia and edema presenting in the first 0-3 months of life,may be caused by congenital syphilis,toxoplasmosis,or congenital viral infections(such as cytomegalovirus).However,the majority of CNS cases are caused by monogenic defects of structural proteins that form the glomerular fi ltration barrier in the kidneys.Since 1998,an increasing number of genetic defects have been identifi ed for their involvements in the pathogenesis of CNS,including NPHS1,NPHS2,WT1,PLCE1,and LAMB2.Data sources:We searched databases such as PubMed,Elsevier and Wanfang with the following key words:congenital nephrotic syndrome,proteinuria,infants,neonate,congenital infection,mechanism and treatment;and we selected those publications written in English that we judged to be relevant to the topic of this review.Results:Based on the data present in the literature,we reviewed the following topics:1)Infection associated CNS including congenital syphilis,congenital toxoplasmosis,and congenital cytomegalovirus infection;2)genetic CNS including mutation of NPHS1(Nephrin),NPHS2(Podocin),WT1,LAMB2(Laminin-β2),PLCE1(NPHS3);3)Other forms of CNS including maternal systemic lupus erythematosus,mercury poisoning,renal vein thrombosis,neonatal alloimmunization against neutral endopeptidase.Conclusions:At present,the main challenge in CNS is to identify the cause of disease for individual patients.To make a definitive diagnosis,with the exclusion of infection-related CNS and maternal-associated disorders,pathology,family history,inheritance mode,and other accompanying congenital malformations are sometimes,but not always,useful indicators for diagnosing genetic CNS.Next-generation sequencing would be a more effective method for diagnosing genetic CNS in some patients,however,there are still some challenges with next-generation sequencing that need to be resolved in the future.

Small-animal PET demonstrates brain metabolic change after using bevacizumab in a rat model of cerebral ischemic injury

ABSTRACT To evaluate the effect of bevacizumab on cerebral ischemia, we used 2-deoxy-2-18F-fluoro-D-glucose （18F-FDG） small-animal positron emission tomography （PET） in the middle cerebral artery occlusion （MCAO） rat model. After baseline neurologic function tests and PET studies, MCAO Sprague-Dawley rats received bevacizumab or normal saline （controls）. Weekly PET imaging and neurologic function tests showed that the 18F-FDG accumulation in the bevacizumab group was similar to that in the controls during the first 2 weeks, but lower than in controls at weeks 3 and 4. However, no difference was found in neurological scores between the groups. The number of von Willebrand factor-positive cells in the bevacizumab group was lower than that in controls. The expression of vascular endothelial growth factor was higher than in controls at week 4. These results suggested that bevacizumab does not influence functional recovery in this model of cerebral ischemia during a 4-week period, but inhibits vascular formation and metabolic recovery, which may be considered in cancer patients with a recent ischemic stroke.

EGFR signaling augments TLR4 cell surface expression and function in macrophages via regulation of Rab5a activation

Dear Editor,oll-like receptor 4(TLR4)is a key receptor sensing bacterial lipopolysaccharide(LPS),and is the most investigated member of the Tol-like receptor family(Kawai and Akira,2007;Kayagaki et al,2013;Klein et al.,2015).Cell surface TLR4 expression is determined by the balance between receptor trafficking from the Golgi apparatus to the cell membrane,and internalization of the cell surface receptor into endosomal compartments(Saltoh,2009).In bone mar-row-derived macrophages(BMDM),we observed LPS-in-duced EGFR phosphorylation on the surface of BMDM,and this was inhibited by pretreatment with PD168393 or TAPI-1(Fig.S1).Next,we measured dynamic changes in cell sur-face TLR4 expression after LPS treatment.At6,12,and 24 h after LPS treatment,TLR4 expression on the surface of BMDM was increased^2-,~6-,and^9-fold,respectively,as compared with controls.

Mortality and Morbidity of Extremely Low Birth Weight Infants in the Mainland of China： A Multi-center Study

Background： With the progress ofperinatal medicine and neonatal technology, more and more extremely low birth weight （ELBW） survived all over the world. This study was designed to investigate the short-term ontcomes of ELBW infants during their Neonatal Intensive Care Unit （NICU） stay in the mainland of China. Methods： All infants admitted to 26 NICUs with a birth weight （BW） 〈1000 g were included between January 1,2011 and December 31,2011. All the data were collected retrospectively from clinical records by a prospectively designed questionnaire. The data collected from each NICU transmitted to the main institution where the results were aggregated and analyzed. Categorical variables were performed with Pearson Chi-square test. Binary Logistic regression analysis was used to detect risk factors. Results： A total of 258 ELBW infants were admitted to 26 NICUs, of whom the mean gestational age （GA） was 28.1 ± 2.2 weeks, and the mean BW was 868 ± 97 g. The overall survival rate at discharge was 50.0%. Despite aggressive treatment 60 infants （23.3%） died and another 69 infants （26.7%） died after medical care withdrawal. Furthermore, the survival rate was significantly higher in coastal areas than inland areas （53.6% vs. 35.3%, P = 0.019）. BW 〈750 g and GA 〈28 weeks were the largest risk factors, and being small for gestational age was a protective factor related to mortality. Respiratory distress syndrome was the most common complication. The incidence of patent ductus arteriosus, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, retinopathy of prematurity was 26.2%, 33.7%, 6.7%, 48.1%, and 41.4%, respectively. Ventilator associated pneumonia was the most common hospital acquired infection during hospitalization. Conclusions： Our study was the first survey that revealed the present status of ELBW infants in the mainland of China. The mortality and morbidity of ELBW infants remained high as compared to other developed countries.

AIFM1 variants associated with auditory neuropathy spectrum disorder cause apoptosis due to impaired apoptosis-inducing factor dimerization

Auditory neuropathy spectrum disorder(ANSD)represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function,but with the preservation of outer hair cell function.ANSD represents up to 15%of individuals with hearing impairments.Through mutation screening,bioinformatic analysis and expression studies,we have previously identified several apoptosis-inducing factor(AIF)mitochondria-associated 1(AIFM1)variants in ANSD families and in some other sporadic cases.Here,to elucidate the pathogenic mechanisms underlying each AIFM1 variant,we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)system and constructed AIF-wild type(WT)and AIF-mutant(mut)(p.T260A,p.R422W,and p.R451Q)stable transfection cell lines.We then analyzed AIF structure,coenzyme-binding affinity,apoptosis,and other aspects.Results revealed that these variants resulted in impaired dimerization,compromising AIF function.The reduction reaction of AIF variants had proceeded slower than that of AIF-WT.The average levels of AIF dimerization in AIF variant cells were only 34.5%-49.7%of that of AIF-WT cells,resulting in caspase-independent apoptosis.The average percentage of apoptotic cells in the variants was 12.3%-17.9%,which was significantly higher than that(6.9%-7.4%)in controls.However,nicotinamide adenine dinucleotide(NADH)treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells.Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD,and introduce NADH as a potential drug for ANSD treatment.Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.