BACKGROUND We report a rare case of primary clinical presentation featuring elevated creatine kinase(CK)levels in a neonate,which is associated with the LAMA2 gene.In this case,a heterozygous mutation in exon5 of the ...BACKGROUND We report a rare case of primary clinical presentation featuring elevated creatine kinase(CK)levels in a neonate,which is associated with the LAMA2 gene.In this case,a heterozygous mutation in exon5 of the LAMA2 gene,c.715C>G(resulting in a change of nucleotide number 715 in the coding region from cytosine to gua-nine),induced an amino acid alteration p.R239G(No.239)in the patient,repre-senting a missense mutation.This observation may be elucidated by the neonatal creatine monitoring mechanism,a phenomenon not previously reported.CASE SUMMARY We analysed the case of a neonate presenting solely with elevated CK levels who was eventually discharged after supportive treatment.The chief complaint was identification of increased CK levels for 15 d and higher CK values for 1 d.Ad-mission occurred at 18 d of age,and despite prolonged treatment with creatine and vitamin C,the elevated CK levels showed limited improvement.Whole exo-me sequencing revealed the presence of a c.715C>G mutation in LAMA2 in the newborn,correlating with a clinical phenotype.However,the available informa-tion offers insufficient evidence for clinical pathogenicity.CONCLUSION Mutations in LAMA2 are associated with the clinical phenotype of increased neonatal CK levels,for which no specific treatment exists.Whole genome sequen-cing facilitates early diagnosis.展开更多
Background This study aimed to identify survival risk factors in Chinese children with hepatoblastoma(HB)and assess the effectiveness of the new treatment protocol proposed by the Chinese Children's Cancer Group(C...Background This study aimed to identify survival risk factors in Chinese children with hepatoblastoma(HB)and assess the effectiveness of the new treatment protocol proposed by the Chinese Children's Cancer Group(CCCG)in 2016.Methods A multicenter,prospective study that included 399 patients with HB from January 2015 to June 2020 was con-ducted.Patient demographics,treatment protocols,and other related information were collected.Cox regression models and Kaplan-Meier curve methods were used.Results The 4-year event-free survival(EFS)and overall survival(OS)were 76.9 and 93.5%,respectively.The 4-year EFS rates for the very-low-risk,low-risk,intermediate-risk,and high-risk groups were 100%,91.6%,81.7%,and 51.0%,respec-tively.The 4-year 0S was 100%,97.3%,94.4%,and 86.8%,respectively.Cox regression analysis found that age,tumor rupture(R+),and extrahepatic tumor extension(E+)were independent prognostic factors.A total of 299 patients had complete remission,and 19 relapsed.Patients with declining alpha-fetoprotein(AFP)>75%after the first two cycles of neoadjuvant chemotherapy had a better EFS and OS than those≤75%.Conclusions The survival outcome of HB children has dramatically improved since the implementation of CCCG-HB-2016 therapy.Age≥8 years,R+,and E+were independent risk factors for prognosis.Patients with a declining AFP>75%after the first two cycles of neoadjuvant chemotherapy had better EFS and OS.展开更多
Autophagy has been suggested to participate in the pathology of hypoxic-ischemic brain damage(HIBD).However,its regulatory role in HIBD remains unclear and was thus examined here using a rat model.To induce HIBD,the...Autophagy has been suggested to participate in the pathology of hypoxic-ischemic brain damage(HIBD).However,its regulatory role in HIBD remains unclear and was thus examined here using a rat model.To induce HIBD,the left common carotid artery was ligated in neonatal rats,and the rats were subjected to hypoxia for 2 hours.Some of these rats were intraperitoneally pretreated with the autophagy inhibitor 3-methyladenine(10 m M in 10 μL) or the autophagy stimulator rapamycin(1 g/kg) 1 hour before artery ligation.Our findings demonstrated that hypoxia-ischemia-induced hippocampal injury in neonatal rats was accompanied by increased expression levels of the autophagy-related proteins light chain 3 and Beclin-1 as well as of the AMPA receptor subunit GluR 1,but by reduced expression of GluR 2.Pretreatment with the autophagy inhibitor 3-methyladenine blocked hypoxia-ischemia-induced hippocampal injury,whereas pretreatment with the autophagy stimulator rapamycin significantly augmented hippocampal injury.Additionally,3-methyladenine pretreatment blocked the hypoxia-ischemia-induced upregulation of Glu R1 and downregulation of GluR2 in the hippocampus.By contrast,rapamycin further elevated hippocampal Glu R1 levels and exacerbated decreased GluR2 expression levels in neonates with HIBD.Our results indicate that autophagy inhibition favors the prevention of HIBD in neonatal rats,at least in part,through normalizing Glu R1 and GluR2 expression.展开更多
Hypoxic injuries during fetal distress have been shown to cause reduced expression of micro RNA-27a(mi R-27a),which regulates sensitivity of cortical neurons to apoptosis.We hypothesized that miR-27 a overexpression...Hypoxic injuries during fetal distress have been shown to cause reduced expression of micro RNA-27a(mi R-27a),which regulates sensitivity of cortical neurons to apoptosis.We hypothesized that miR-27 a overexpression attenuates hypoxia- and ischemia-induced neuronal apoptosis by regulating FOXO1,an important transcription factor for regulating the oxidative stress response.miR-27 a mimic was transfected into hippocampal neurons to overexpress miR-27 a.Results showed increased hippocampal neuronal viability and decreased caspase-3 expression.The luciferase reporter gene system demonstrated that mi R-27 a directly binded to FOXO1 3′UTR in hippocampal neurons and inhibited FOXO1 expression,suggesting that FOXO1 was the target gene for mi R-27 a.These findings confirm that mi R-27 a protects hippocampal neurons against oxygen-glucose deprivation-induced injuries.The mechanism might be mediated by modulation of FOXO1 and apoptosis-related gene caspase-3 expression.展开更多
Clock genes are involved in circadian rhythm regulation, and surviving newborns with hypoxic-ischemic encephalopathy may present with sleep-wake cycle reversal. This study aimed to determine the expression of the cloc...Clock genes are involved in circadian rhythm regulation, and surviving newborns with hypoxic-ischemic encephalopathy may present with sleep-wake cycle reversal. This study aimed to determine the expression of the clock genes Clock and Bmall, in the pineal gland of rats with hypoxic-ischemic brain damage. Results showed that levels of Clock mRNA v^re not significantly changed within 48 hours after cerebral hypoxia and ischemia. Expression levels of CLOCK and BMAL1 protein were significantly higher after 48 hours. The levels of Bmall mRNA reached a peak at 36 hours, but were significantly reduced at 48 hours. Experimental findings indicate that Clock and Bmall genes were indeed expressed in the pineal glands of neonatal rats. At the initial stage (within 36 hours) of hypoxic-ischemic brain damage, only slight changes in the expression levels of these two genes were detected, followed by significant changes at 36-48 hours. These changes may be associated with circadian rhythm disorder induced by hypoxic-ischemic brain damage.展开更多
AIM:To analyze the retinal proteomes with and without conbercept treatments in mice with oxygen-induced retinopathy(OIR)and identify proteins involved in the molecular mechanisms mediated by conbercept.METHODS:OIR was...AIM:To analyze the retinal proteomes with and without conbercept treatments in mice with oxygen-induced retinopathy(OIR)and identify proteins involved in the molecular mechanisms mediated by conbercept.METHODS:OIR was induced in fifty-six C57 BL/6 J mouse pups and randomly divided into four groups.Group 1:Normal17(n=7),mice without OIR and treated with normal air.Group 2:OIR12/EXP1(n=14),mice received 75%oxygen from postnatal day(P)7 to 12.Group 3:OIR17/Control(n=14),mice received 75%oxygen from P7 to P12 and then normal air to P17.Group 4:Lang17/EXP2(n=21),mice received 75%oxygen from P7 to P12 with intravitreal injection of 1μL conbercept at the concentration of 10 mg/m L at P12,and then normal air from P12 to P17.Liquid ChromatographyMass Spectrometry(LC-MS)/MS data were reviewed to find proteins that were up-regulated after the conbercept treatment.Gene ontology(GO)analysis was performed of conbercept-mediated changes in proteins involved in single-organism processes,biological regulation,cellular processes,immune responses,metabolic processes,locomotion and multiple-organism processes.RESULTS:Conbercept induced a reversal of hypoxiainducible factor 1 signaling pathway as revealed by the Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis and also induced down-regulation of proteins involved in blood coagulation and fibrin clot formation as demonstrated by the Database for Annotation,Visualization and Integrated Discovery(DAVID)and the stimulation of interferon genes studies.These appear to be risk factors of retinal fibrosis.Additional conbercept-specific fibrosis risk factors were also identified and may serve as therapeutic targets for fibrosis.CONCLUSION:Our studies reveal that many novel proteins are differentially regulated by conbercept.The new insights may warrant a valuable resource for conbercept treatment.展开更多
Background Respiratory syncytial virus(RSV)is the leading global cause of respiratory infections and is responsible for about 3 million hospitalizations and more than 100,000 deaths annually in children younger than 5...Background Respiratory syncytial virus(RSV)is the leading global cause of respiratory infections and is responsible for about 3 million hospitalizations and more than 100,000 deaths annually in children younger than 5 years,representing a major global healthcare burden.There is a great unmet need for new agents and universal strategies to prevent RSV infections in early life.A multidisciplinary consensus development group comprising experts in epidemiology,infectious diseases,respiratory medicine,and methodology aims to develop the current consensus to address clinical issues of RSV infections in children.Data sources The evidence searches and reviews were conducted using electronic databases,including PubMed,Embase,Web of Science,and the Cochrane Library,using variations in terms for"respiratory syncytial virus","RSV","lower respiratory tract infection","bronchiolitis","acute","viral pneumonia","neonatal","infant""children",and"pediatric".Results Evidence-based recommendations regarding diagnosis,treatment,and prevention were proposed with a high degree of consensus.Although supportive care remains the cornerstone for the management of RSV infections,new monoclonal antibodies,vaccines,drug therapies,and viral surveillance techniques are being rolled out.Conclusions This consensus,based on international and national scientific evidence,reinforces the current recommendations and integrates the recent advances for optimal care and prevention of RSV infections.Further improvements in the management of RSV infections will require generating the highest quality of evidence through rigorously designed studies that possess little bias and sufficient capacity to identify clinically meaningful end points.展开更多
To the Editor,Cytarabine is one of the most used drugs for the treatment of hematological malignancies such as leukemia and non-Hodgkin's lymphoma.In cells,cytarabine is activated into ara-CTP,which can replace de...To the Editor,Cytarabine is one of the most used drugs for the treatment of hematological malignancies such as leukemia and non-Hodgkin's lymphoma.In cells,cytarabine is activated into ara-CTP,which can replace deoxycytidine triphosphate(dCTP)and become incorporated into the DNA of proliferating cells.Thus,it can block DNA synthesis,resulting in proliferation arrest and cell death.展开更多
Secondary brain damage caused by hyperactivation of autophagy and inflammatory responses in neurons plays an important role in hypoxic-ischemic brain damage(HIBD).Although previous studies have implicated Toll-like re...Secondary brain damage caused by hyperactivation of autophagy and inflammatory responses in neurons plays an important role in hypoxic-ischemic brain damage(HIBD).Although previous studies have implicated Toll-like receptor 4(TLR4)and nuclear factor kappa-B(NF-κB)in the neuroinflammatory response elicited by brain injury,the role and mechanisms of the TLR4-mediated autophagy signaling pathway in neonatal HIBD are still unclear.We hypothesized that this pathway can regulate brain damage by modulating neuron autophagy and neuroinflammation in neonatal rats with HIBD.Hence,we established a neonatal HIBD rat model using the Rice-Vannucci method,and injected 0.75,1.5,or 3 mg/kg of the TLR4 inhibitor resatorvid(TAK-242)30 minutes after hypoxic ischemia.Our results indicate that administering TAK-242 to neonatal rats after HIBD could significantly reduce the infarct volume and the extent of cerebral edema,alleviate neuronal damage and neurobehavioral impairment,and decrease the expression levels of TLR4,phospho-NF-κB p65,Beclin-1,microtubule-associated protein l light chain 3,tumor necrosis factor-α,and interleukin-1βin the hippocampus.Thus,TAK-242 appears to exert a neuroprotective effect after HIBD by inhibiting activation of autophagy and the release of inflammatory cytokines via inhibition of the TLR4/NF-κB signaling pathway.This study was approved by the Laboratory Animal Ethics Committee of Affiliated Hospital of Yangzhou University,China(approval No.20180114-15)on January 14,2018.展开更多
With improvements in care of at-risk neonates, more and more children survive. This makes it increasingly important to assess, soon after birth, the prognosis of children with hypoxic-ischemic encephalopathy. Computed...With improvements in care of at-risk neonates, more and more children survive. This makes it increasingly important to assess, soon after birth, the prognosis of children with hypoxic-ischemic encephalopathy. Computed tomography, ultrasound, and conventional magnetic resonance imaging are helpful to diagnose brain injury, but cannot quantify white matter damage. In this study, ten full-term infants without brain injury and twenty-two full-term neonates with hypoxic-ischemic encephalopathy (14 moderate cases and 8 severe cases) underwent diffusion tensor imaging to assess its feasibility in evaluating white matter damage in this condition. Results demonstrated that fractional anisotropy, voxel volume, and number of fiber bundles were different in some brain areas between infants with brain injury and those without brain injury. The correlation between fractional anisotropy values and neonatal behavioral neurological assessment scores was closest in the posterior limbs of the internal capsule. We conclude that diffusion tensor imaging can quantify white matter injury in neonates with hypoxic-ischemic encephalopathy.展开更多
Acute myeloid leukemia(AML) is a heterogeneous disease characterized by the accu.mulation of immature myeloid progenitor cells in the bone marrow,compromising of normal hematopoi.esis and ultimately resulting in bone ...Acute myeloid leukemia(AML) is a heterogeneous disease characterized by the accu.mulation of immature myeloid progenitor cells in the bone marrow,compromising of normal hematopoi.esis and ultimately resulting in bone marrow failure.Chemotherapy is the mainstay treatment for all AML patients,however,drug resistance and clinical relapse limits its efficacy.The 5-year survival rate of AML patients is only 26.6%.Survival rates are even lower among patients ages 65 to 74 years(5.3%) and 75 years or older(1.6%).Therefore,exploring novel therapeutic agents is urgent for improving the outcome of patients with AML.Saponins are amphipathic glycosides found in traditional Chinese medicines.In the present study,we isolated a panel of saponins from Paris forrestii(Takht.) H.Li,a unique plant found in Tibet and Yunnan provinces,China.By examining their activities in suppressing acute myeloid leukemia cell proliferation,total saponins from Paris forrestii(TSPf) displayed more potent activity than individual ones.TSPf induced more than 40% AML cell apoptosis within 24 h and decreased the viability of all leukemia cell lines.TSPf-induced apoptosis was confirmed by both Annexin V staining and caspase-3 activation.TSPf downregulated pro-survival proteins Mcl-1,Bcl-xL and Bcl-2,but upreg.ulated the expression of tumor suppressor proteins p53,p27,Bax and Beclin 1.The AKT/mTOR signaling pathway is frequently over activated in various AML cells,and TSPf was found to suppress the activa.tion of both AKT and mTOR,but had no effects on their total protein expression.This was further con.firmed by the inactivation of 4 EBP-1 and p70 S6 K,two typical downstream signal molecules in the AKT/mTOR pathway.More specifically,TSPf-inactivated AKT/mTOR signaling was found to be associated with downregulated RNF6,a recently identified oncogene in AML.RNF6 activated AKT/mTOR,and consistently,knockdown of RNF6 led to inactivation of the AKT/mTOR pathway.Furthermore,TSPf suppressed the growth of AML xenografts in nude mice models.Oral administration of 100 mg · kg^(-1) body weight almost fully suppressed tumor growth within 14 d,without gross toxicity.This study thus demonstrated that TSPf displays potent anti-AML activity by suppressing the RNF6/AKT/mTOR pathway.Given its low toxicity,TSPf could be developed for the treatment of AML.展开更多
Dear Editor,R-spondin3(RSPO3)is essential for vascular development and angiogenesis.Analyzing RSPO3-knockout embryos revealed severe vascular defects in the placenta(Aoki et al.2007).In both Xenopus and murine embryos...Dear Editor,R-spondin3(RSPO3)is essential for vascular development and angiogenesis.Analyzing RSPO3-knockout embryos revealed severe vascular defects in the placenta(Aoki et al.2007).In both Xenopus and murine embryos,RSPO3 KO led to significant vascular defects(Kazanskaya et al.2008)and embryonic death(Kazanskaya et al.2008).In the placenta,RSPO3 could promote vascular endothelial growth factor(VEGF)expression(Kazanskaya et al.2008).RSPO3 is a ligand of low-density lipoprotein receptor-related protein 6(LRP6)and leucine-rich repeat G protein-coupled receptor 4(LGR4)to form a multiple ligands-receptors-cluster with Wnt and frizzled(FzD),thereby activating and amplifying downstreamβ-catenin signaling(in and Yoon 2012;Tocci et al.2020).展开更多
Approximately 31%of patients with 22q11.2 deletion syndrome(22q11.2DS)have genitourinary system disorders and 6%of them have undescended testes.Haploinsufficiency of genes on chromosome 22q11.2 might contribute to the...Approximately 31%of patients with 22q11.2 deletion syndrome(22q11.2DS)have genitourinary system disorders and 6%of them have undescended testes.Haploinsufficiency of genes on chromosome 22q11.2 might contribute to the risk of 22q11.2DS.In this study,we used mice with single-allele deletion in mitochondrial ribosomal protein L4o(Mrpl40-)as models to investigate the function of Mrpl40 in testes and spermatozoa development.The penetrance of cryptorchidism in Mrpl40+-mice was found to be higher than that in wild-type(WT)counterparts.Although the weight of testes was not significantly different between the WT and Mrpl40+-mice,the structure of seminiferous tubules and mitochondrial morphology was altered in the Mrpl40+-mice.Moreover,the concentration and motility of spermatozoa were significantly decreased in the Mrpl4O+-mice.In addition,data-independent acquisition mass spectrometry indicated that the expression of genes associated with male infertility was altered in Mrpl40+-testes.Our study demonstrated the important role of Mrpl40 in testicular structure and spermatozoa motility and count.These findings suggest that Mrpl4o is potentially a novel therapeutic target for cryptorchidism and decreased motility and count of spermatozoa.展开更多
Sepsis is a life-threatening organ dysfunction characterized by severe systemic inflammatory response to infection.Effective treatment of bacterial sepsis remains a paramount clinical challenge,due to its astonishingl...Sepsis is a life-threatening organ dysfunction characterized by severe systemic inflammatory response to infection.Effective treatment of bacterial sepsis remains a paramount clinical challenge,due to its astonishingly rapid progression and the prevalence of bacterial drug resistance.展开更多
Objective:To observe the effect of electro-acupuncture(EA)on tumor necrosis factor-α(TNF-α) and vascular endothelial growth factor(VEGF)in peripheral blood and joint synovia in patients with rheumatoid arthri...Objective:To observe the effect of electro-acupuncture(EA)on tumor necrosis factor-α(TNF-α) and vascular endothelial growth factor(VEGF)in peripheral blood and joint synovia in patients with rheumatoid arthritis(RA)to verify the clinical efficacy of EA.Methods:Adopting randomized controlled principle,the 63 RA patients enrolled were assigned to two groups,the 32 patients in the EA group were treated with EA,and the 31 patients in the simple needling(SN)group treated with simple needling.According to the integral-local combining method,the acupoints were selected mainly from yang-meridian and local Ashi points(pain-point).EA or SN was applied every other day,10 times as a course,and each patient received a total of 3 courses of treatment. Results:Blood and synovial levels of TNF-αand VEGF were reduced significantly after treatment in both groups.The lowering(absolute value and difference value)of TNF-αas well as the absolute value of VEGF, either in blood or in synovia,were similar in the two groups(P0.05);but the lowering of VEGF after treatment was more significant in the EA group than that in the SN group(P0.05).Conclusion:EA could effectively lower the contents of TNF-αand VEGF in peripheral blood and joint synovia to improve the internal environment for genesis and development of RA,so as to enhance the clinical therapeutic effectiveness.展开更多
In the present study, three new triterpenoids, 23-hydroxyurs-12, 18-dien-28-oic acid 3β-O-α-L-arabinopyranoside(1), 23-hydroxyurs-12, 18-dien-28-oic acid 3β-O-β-D-glucuronopyranoside-6-O-methyl ester(2), and urs-1...In the present study, three new triterpenoids, 23-hydroxyurs-12, 18-dien-28-oic acid 3β-O-α-L-arabinopyranoside(1), 23-hydroxyurs-12, 18-dien-28-oic acid 3β-O-β-D-glucuronopyranoside-6-O-methyl ester(2), and urs-12, 18-dien-28-oic acid 3β-O-β-D-glucuronopyranoside-6-O-methyl ester(3), and a known triterpenoid, 3β-hydroxy-urs-2, 18-dien-28-oic acid(4, randialic acid B), were isolated from the aerial parts of Ilex cornuta. Their structures were identified by the spectroscopic analyses(IR, ESI-MS, HR-ESI-MS, and 1D and 2D NMR) and chemical reactions. Compound 4 showed significant cell-protective effects against H_2O_2-induced H9c2 cardiomyocyte injury. Compounds 1-4 did not show any significant DPPH radical scavenging activity.展开更多
Background Macrophage activation syndrome(MAS)is a major cause of morbidity and mortality in pediatric rheumatology.We aimed to further understand the clinical features,treatment,and outcome of MAS in China.Methods A ...Background Macrophage activation syndrome(MAS)is a major cause of morbidity and mortality in pediatric rheumatology.We aimed to further understand the clinical features,treatment,and outcome of MAS in China.Methods A multi-center cohort study was performed in seven hospitals in China from 2012 to 2018.Eighty patients with MAS were enrolled,including 53 cases with systemic juvenile idiopathic arthritis(SJIA-MAS),10 cases of Kawasaki disease(KD-MAS),and 17 cases of connective tissue disease(CTD-MAS).The clinical and laboratory data were collected before(pre-),at onset,and during full-blown stages of MAS.We compared the data among the SJIA-MAS,KD-MAS,and CTD-MAS subjects.Results 51.2%of patients developed MAS when the underlying disease was first diagnosed.In patients with SJIA,22.6%(12/53)were found to have hypotension before the onset of SJIA-MAS.These patients were also found to have significantly increased aspartate aminotransferase(AST)and lactate dehydrogenase(LDH),as well as decreased albumin(P<0.05),but no difference in alanine aminotransferase,ferdtin,and ratio of ferritin/erythrocyte sedimentation rate(ESR)at onset of MAS when compared to pre-MAS stages of the disease.In addition,ferritin and ratio of ferritin/ESR were significantly elevated in patients at full-blown stages of SJIA-MAS compared to pre-MAS stage.Significantly increased ferritin and ratio of ferritin/ESR were also observed in patients with SJIA compared to in KD and CTD.Receiver-operating characteristic analysis showed that 12,217.5μg/L of ferritin and 267.5 of ferritin/ESR ratio had sensitivity(80.0%and 90.5%)and specificity(88.2%and 86.7%),respectively,for predicting full-blown SJIA-MAS.The majority of the patients received corticosteroids(79/80),while biologic agents were used in 12.5%(10/80)of cases.Tocilizumab was the most commonly selected biologic agent.The overall mortality rate was 7.5%.Conclusions About half of MAS occurred when the underlying autoimmune diseases(SJIA,KD,and CTD)were first diagnosed.Hypotension could be an important manifestation before MAS diagnosis.Decreased albumin and increased AST,LDH,ferritin,and ratio of ferritin/ESR could predict the onset or full blown of MAS in patient with SJIA.展开更多
Background Acute hypoxemic respiratory failure (AHRF) often develops acute respiratory distress syndrome (ARDS), and its incidence and mortalities in critically ill pediatric patients in China were 2% and 40% resp...Background Acute hypoxemic respiratory failure (AHRF) often develops acute respiratory distress syndrome (ARDS), and its incidence and mortalities in critically ill pediatric patients in China were 2% and 40% respectively. This study aimed at prospectively investigating incidence, causes, mortality and its risk factors, and any relationship to initial tidal volume (VT) levels of mechanical ventilation, in children 〈5 years of age with AHRF and ARDS. Methods In 12 consecutive months in 23 pediatric intensive care units (PICU), AHRF and ARDS were identified in those requiring 〉12 hour intratracheal mechanical ventilation and followed up for 90 days or until death or discharge. ARDS was diagnosed according to the American-European Consensus definitions. The mortality and ventilation free days (VFD) were measured as the primary outcome, and major complications, initial disease severity, and burden were measured as the secondary outcome. Results In 13 491 PICU admissions, there were 439 AHRF, of which 345 (78.6%) developed ARDS, resulting in incidences of 3.3% and 2.6%, and corresponding mortalities of 30.3% and 32.8% respectively along with 8.2 and 6.7 times of relative risk of death in those with pneumonia (62.9%) and sepsis (33.7%) as major underlying diseases respectively. No association was found in VT levels during the first 7 days with mortality, nor for V-r at levels 〈6, 6-8, 8-10, and 〉10 ml/kg in the first 3 days with mortality or length of VFD. By binary Logistic regression analyses, higher pediatric risk of mortality score III, higher initial oxygenation index, and age 〈1 year were associated with higher mortality or shorter VFD in AHRF. Conclusions The incidence and mortalities of AHRF and ARDS in children 〈5 years were similar to or lower than the previously reported rates (in age up to 15 years), associated with initial disease severity and other confounders, but causal relationship for the initial VT levels as the independent factor to the major outcome was not found.展开更多
Background The aim of this study is to explore the characteristics of Kawasaki disease(KD)and concurrent pathogens due to a stay-at-home isolation policy during coronavirus disease 2019(COVID-19)epidemic.Methods All p...Background The aim of this study is to explore the characteristics of Kawasaki disease(KD)and concurrent pathogens due to a stay-at-home isolation policy during coronavirus disease 2019(COVID-19)epidemic.Methods All patients with KD admitted between February and April in 2015-2020,were classified into before(group 1,in 2015-2019)and after(group 2,in 2020)isolation groups.A total of 4742 patients[with KD(m=98)and non-KD(n=4644)]referred to Mycoplasma pneumoniae(MP)and virus detection were analyzed in 2020.Clinical characteristics,laboratory data,and 13 pathogens were analyzed retrospectively.Results Group 2 had a significantly increased incidence of KD(0.11%)with 107 patients compared to that of group 1(0.03%)with 493 patients.The comparisons of oral mucosal change,strawberry tongue,desquamation of the fingertips,cervical lymphadenopathy and neutrophil percentage decreased in group 2 compared to group 1.The infection rate of MP increased significantly in group 2(34.7%)compared to group 1(19.3%),while the positive rate of viruses decreased significantly in group 2(5.3%)compared to group 1(14.3%).In 2020,the positive rate of MP infection increased significantly in patients with KD compared to the increase in patients with non-KD.The infection rate of MP for younger children aged less than 3 years old was higher in group 2 than in group 1.Conclusion Compared with the characteristics of KD from 2015 to 2019 years,the incidence of KD was increased in 2020 and was accompanied by a high incidence of MP infection,especially in younger children(less than 3 years old)during the isolation due to COVID-19 pandemic.展开更多
Background Glucocorticoid receptor (GR) is believed to be a major factor in brain maturation and in modulation of a series of brain activity. Hippocampal neurons are abundant in glucocorticoid receptor, and there is...Background Glucocorticoid receptor (GR) is believed to be a major factor in brain maturation and in modulation of a series of brain activity. Hippocampal neurons are abundant in glucocorticoid receptor, and there is significant change in GR expression under certain pathological state. Epilepsy is a special pathological state of the central nervous system. This study aimed to explore the role of GR in epilepsy by observing the change and functions of GR in hippocampus with a basolateral amygdale-electrical kindled rat epilepsy model. Methods Firstly, we established the basolateral amygdale-electrical kindled rat epilepsy model. Then GR mRNA expression in the hippocampus was assayed by semi-quantitative reverse transcription-PCR in this experiment. In addition, the processes of epileptic seizures were observed and electroencephalograms were recorded. One-way analysis of variance (ANOVA) was employed for comparing means of multiple groups, followed Fisher's least significant difference (LSD) for paired comparison. Results The rats were successfully kindled after an average of (13.50+3.99) times electrical stimulation, in which it was showed that GR mRNA expression reduced obviously as compared with the control group and the sham groups (P 〈0.001). The down-regulation of GR mRNA expression was abated or reversed by some anti-epilepsy drugs (P 〈0.001 compared with the epilepsy group), accompanied by attenuation of seizures and improvement of electroencephalograms. Conclusions Down-regulation of hippocampal GR mRNA expression may be related to the kindling. Anti-epilepsy drugs exposure can retard this change.展开更多
基金Supported by The Suzhou Science and Technology Development Plan Guiding Project,No.SZSYYXH-2023-YB5The Suzhou Science and Technology Development Plan Project,No.SKY2023002The Suzhou Key Laboratory of Children's Structural Deformities,No.SZS2022018.
文摘BACKGROUND We report a rare case of primary clinical presentation featuring elevated creatine kinase(CK)levels in a neonate,which is associated with the LAMA2 gene.In this case,a heterozygous mutation in exon5 of the LAMA2 gene,c.715C>G(resulting in a change of nucleotide number 715 in the coding region from cytosine to gua-nine),induced an amino acid alteration p.R239G(No.239)in the patient,repre-senting a missense mutation.This observation may be elucidated by the neonatal creatine monitoring mechanism,a phenomenon not previously reported.CASE SUMMARY We analysed the case of a neonate presenting solely with elevated CK levels who was eventually discharged after supportive treatment.The chief complaint was identification of increased CK levels for 15 d and higher CK values for 1 d.Ad-mission occurred at 18 d of age,and despite prolonged treatment with creatine and vitamin C,the elevated CK levels showed limited improvement.Whole exo-me sequencing revealed the presence of a c.715C>G mutation in LAMA2 in the newborn,correlating with a clinical phenotype.However,the available informa-tion offers insufficient evidence for clinical pathogenicity.CONCLUSION Mutations in LAMA2 are associated with the clinical phenotype of increased neonatal CK levels,for which no specific treatment exists.Whole genome sequen-cing facilitates early diagnosis.
基金supported by the Shanghai Municipal Hospital New Frontier Technology Joint Key Project,Shanghai,China(No.SHDC12019115).
文摘Background This study aimed to identify survival risk factors in Chinese children with hepatoblastoma(HB)and assess the effectiveness of the new treatment protocol proposed by the Chinese Children's Cancer Group(CCCG)in 2016.Methods A multicenter,prospective study that included 399 patients with HB from January 2015 to June 2020 was con-ducted.Patient demographics,treatment protocols,and other related information were collected.Cox regression models and Kaplan-Meier curve methods were used.Results The 4-year event-free survival(EFS)and overall survival(OS)were 76.9 and 93.5%,respectively.The 4-year EFS rates for the very-low-risk,low-risk,intermediate-risk,and high-risk groups were 100%,91.6%,81.7%,and 51.0%,respec-tively.The 4-year 0S was 100%,97.3%,94.4%,and 86.8%,respectively.Cox regression analysis found that age,tumor rupture(R+),and extrahepatic tumor extension(E+)were independent prognostic factors.A total of 299 patients had complete remission,and 19 relapsed.Patients with declining alpha-fetoprotein(AFP)>75%after the first two cycles of neoadjuvant chemotherapy had a better EFS and OS than those≤75%.Conclusions The survival outcome of HB children has dramatically improved since the implementation of CCCG-HB-2016 therapy.Age≥8 years,R+,and E+were independent risk factors for prognosis.Patients with a declining AFP>75%after the first two cycles of neoadjuvant chemotherapy had better EFS and OS.
基金supported by the National Natural Science Foundation of China,No.81471488,81271378,81502157,and 81501291the Key Medical Subjects of Jiangsu Province of China,No.XK201120+3 种基金the Jiangsu Province Key Research and Development of Special Funds in China,No.BE2015644the Science and Technology Project of Suzhou City of China,No.SYSD2013105,SYS201446,SYS201441the Public Health Technology Project of Suzhou City of China,No.SS201536the Department of Pediatrics Clinical Center of Suzhou City of China,No.Szzx201504
文摘Autophagy has been suggested to participate in the pathology of hypoxic-ischemic brain damage(HIBD).However,its regulatory role in HIBD remains unclear and was thus examined here using a rat model.To induce HIBD,the left common carotid artery was ligated in neonatal rats,and the rats were subjected to hypoxia for 2 hours.Some of these rats were intraperitoneally pretreated with the autophagy inhibitor 3-methyladenine(10 m M in 10 μL) or the autophagy stimulator rapamycin(1 g/kg) 1 hour before artery ligation.Our findings demonstrated that hypoxia-ischemia-induced hippocampal injury in neonatal rats was accompanied by increased expression levels of the autophagy-related proteins light chain 3 and Beclin-1 as well as of the AMPA receptor subunit GluR 1,but by reduced expression of GluR 2.Pretreatment with the autophagy inhibitor 3-methyladenine blocked hypoxia-ischemia-induced hippocampal injury,whereas pretreatment with the autophagy stimulator rapamycin significantly augmented hippocampal injury.Additionally,3-methyladenine pretreatment blocked the hypoxia-ischemia-induced upregulation of Glu R1 and downregulation of GluR2 in the hippocampus.By contrast,rapamycin further elevated hippocampal Glu R1 levels and exacerbated decreased GluR2 expression levels in neonates with HIBD.Our results indicate that autophagy inhibition favors the prevention of HIBD in neonatal rats,at least in part,through normalizing Glu R1 and GluR2 expression.
基金supported by the National Natural Science Foundation of China,No.81101159the Natural Science Foundation of Jiangsu Province of China,No.BK20151268
文摘Hypoxic injuries during fetal distress have been shown to cause reduced expression of micro RNA-27a(mi R-27a),which regulates sensitivity of cortical neurons to apoptosis.We hypothesized that miR-27 a overexpression attenuates hypoxia- and ischemia-induced neuronal apoptosis by regulating FOXO1,an important transcription factor for regulating the oxidative stress response.miR-27 a mimic was transfected into hippocampal neurons to overexpress miR-27 a.Results showed increased hippocampal neuronal viability and decreased caspase-3 expression.The luciferase reporter gene system demonstrated that mi R-27 a directly binded to FOXO1 3′UTR in hippocampal neurons and inhibited FOXO1 expression,suggesting that FOXO1 was the target gene for mi R-27 a.These findings confirm that mi R-27 a protects hippocampal neurons against oxygen-glucose deprivation-induced injuries.The mechanism might be mediated by modulation of FOXO1 and apoptosis-related gene caspase-3 expression.
基金supported by grants from the Foundation for Advancing Medical Sciences of the Health Department, Jiangsu Province, No. Z200519the Project for Social Development of Suzhou, No. SSZ0230
文摘Clock genes are involved in circadian rhythm regulation, and surviving newborns with hypoxic-ischemic encephalopathy may present with sleep-wake cycle reversal. This study aimed to determine the expression of the clock genes Clock and Bmall, in the pineal gland of rats with hypoxic-ischemic brain damage. Results showed that levels of Clock mRNA v^re not significantly changed within 48 hours after cerebral hypoxia and ischemia. Expression levels of CLOCK and BMAL1 protein were significantly higher after 48 hours. The levels of Bmall mRNA reached a peak at 36 hours, but were significantly reduced at 48 hours. Experimental findings indicate that Clock and Bmall genes were indeed expressed in the pineal glands of neonatal rats. At the initial stage (within 36 hours) of hypoxic-ischemic brain damage, only slight changes in the expression levels of these two genes were detected, followed by significant changes at 36-48 hours. These changes may be associated with circadian rhythm disorder induced by hypoxic-ischemic brain damage.
基金Supported by the National Natural Science Foundation of China(No.81671641)Suzhou Science and Technology Fund of China(No.SYS2020137)。
文摘AIM:To analyze the retinal proteomes with and without conbercept treatments in mice with oxygen-induced retinopathy(OIR)and identify proteins involved in the molecular mechanisms mediated by conbercept.METHODS:OIR was induced in fifty-six C57 BL/6 J mouse pups and randomly divided into four groups.Group 1:Normal17(n=7),mice without OIR and treated with normal air.Group 2:OIR12/EXP1(n=14),mice received 75%oxygen from postnatal day(P)7 to 12.Group 3:OIR17/Control(n=14),mice received 75%oxygen from P7 to P12 and then normal air to P17.Group 4:Lang17/EXP2(n=21),mice received 75%oxygen from P7 to P12 with intravitreal injection of 1μL conbercept at the concentration of 10 mg/m L at P12,and then normal air from P12 to P17.Liquid ChromatographyMass Spectrometry(LC-MS)/MS data were reviewed to find proteins that were up-regulated after the conbercept treatment.Gene ontology(GO)analysis was performed of conbercept-mediated changes in proteins involved in single-organism processes,biological regulation,cellular processes,immune responses,metabolic processes,locomotion and multiple-organism processes.RESULTS:Conbercept induced a reversal of hypoxiainducible factor 1 signaling pathway as revealed by the Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis and also induced down-regulation of proteins involved in blood coagulation and fibrin clot formation as demonstrated by the Database for Annotation,Visualization and Integrated Discovery(DAVID)and the stimulation of interferon genes studies.These appear to be risk factors of retinal fibrosis.Additional conbercept-specific fibrosis risk factors were also identified and may serve as therapeutic targets for fibrosis.CONCLUSION:Our studies reveal that many novel proteins are differentially regulated by conbercept.The new insights may warrant a valuable resource for conbercept treatment.
文摘Background Respiratory syncytial virus(RSV)is the leading global cause of respiratory infections and is responsible for about 3 million hospitalizations and more than 100,000 deaths annually in children younger than 5 years,representing a major global healthcare burden.There is a great unmet need for new agents and universal strategies to prevent RSV infections in early life.A multidisciplinary consensus development group comprising experts in epidemiology,infectious diseases,respiratory medicine,and methodology aims to develop the current consensus to address clinical issues of RSV infections in children.Data sources The evidence searches and reviews were conducted using electronic databases,including PubMed,Embase,Web of Science,and the Cochrane Library,using variations in terms for"respiratory syncytial virus","RSV","lower respiratory tract infection","bronchiolitis","acute","viral pneumonia","neonatal","infant""children",and"pediatric".Results Evidence-based recommendations regarding diagnosis,treatment,and prevention were proposed with a high degree of consensus.Although supportive care remains the cornerstone for the management of RSV infections,new monoclonal antibodies,vaccines,drug therapies,and viral surveillance techniques are being rolled out.Conclusions This consensus,based on international and national scientific evidence,reinforces the current recommendations and integrates the recent advances for optimal care and prevention of RSV infections.Further improvements in the management of RSV infections will require generating the highest quality of evidence through rigorously designed studies that possess little bias and sufficient capacity to identify clinically meaningful end points.
基金The Foundation of GUSU Health Talent Research Project(Grant/Award Number:GSW2022057)the Key Technology Research and Development Project for Medical and Health Technology Innovation of Soochow(Grant/Award Number:SKY2021049).
文摘To the Editor,Cytarabine is one of the most used drugs for the treatment of hematological malignancies such as leukemia and non-Hodgkin's lymphoma.In cells,cytarabine is activated into ara-CTP,which can replace deoxycytidine triphosphate(dCTP)and become incorporated into the DNA of proliferating cells.Thus,it can block DNA synthesis,resulting in proliferation arrest and cell death.
基金financially supported by the National Natural Science Foundation of China,No.81771625(to XF)the Jiangsu Provincial Key Medical Discipline of China,No.ZDXKA2016013(to XF)the Pediatric Clinical Center of Suzhou City of China,No.Szzx201504(to XF)
文摘Secondary brain damage caused by hyperactivation of autophagy and inflammatory responses in neurons plays an important role in hypoxic-ischemic brain damage(HIBD).Although previous studies have implicated Toll-like receptor 4(TLR4)and nuclear factor kappa-B(NF-κB)in the neuroinflammatory response elicited by brain injury,the role and mechanisms of the TLR4-mediated autophagy signaling pathway in neonatal HIBD are still unclear.We hypothesized that this pathway can regulate brain damage by modulating neuron autophagy and neuroinflammation in neonatal rats with HIBD.Hence,we established a neonatal HIBD rat model using the Rice-Vannucci method,and injected 0.75,1.5,or 3 mg/kg of the TLR4 inhibitor resatorvid(TAK-242)30 minutes after hypoxic ischemia.Our results indicate that administering TAK-242 to neonatal rats after HIBD could significantly reduce the infarct volume and the extent of cerebral edema,alleviate neuronal damage and neurobehavioral impairment,and decrease the expression levels of TLR4,phospho-NF-κB p65,Beclin-1,microtubule-associated protein l light chain 3,tumor necrosis factor-α,and interleukin-1βin the hippocampus.Thus,TAK-242 appears to exert a neuroprotective effect after HIBD by inhibiting activation of autophagy and the release of inflammatory cytokines via inhibition of the TLR4/NF-κB signaling pathway.This study was approved by the Laboratory Animal Ethics Committee of Affiliated Hospital of Yangzhou University,China(approval No.20180114-15)on January 14,2018.
基金supported by a grant from the Clinical Medicine Science and Technology Projects in Jiangsu Province of China,No.BL2014037a grant from the Changzhou City Science and Technology Support Plan in China,No.CE20165027+1 种基金a grant from the Changzhou Health Development Planning Commission Major Projects in China,No.ZD201515the Changzhou High-Level Health Personnel Training Project Funding
文摘With improvements in care of at-risk neonates, more and more children survive. This makes it increasingly important to assess, soon after birth, the prognosis of children with hypoxic-ischemic encephalopathy. Computed tomography, ultrasound, and conventional magnetic resonance imaging are helpful to diagnose brain injury, but cannot quantify white matter damage. In this study, ten full-term infants without brain injury and twenty-two full-term neonates with hypoxic-ischemic encephalopathy (14 moderate cases and 8 severe cases) underwent diffusion tensor imaging to assess its feasibility in evaluating white matter damage in this condition. Results demonstrated that fractional anisotropy, voxel volume, and number of fiber bundles were different in some brain areas between infants with brain injury and those without brain injury. The correlation between fractional anisotropy values and neonatal behavioral neurological assessment scores was closest in the posterior limbs of the internal capsule. We conclude that diffusion tensor imaging can quantify white matter injury in neonates with hypoxic-ischemic encephalopathy.
基金supported by Natural Science Foundation of China(81770154)
文摘Acute myeloid leukemia(AML) is a heterogeneous disease characterized by the accu.mulation of immature myeloid progenitor cells in the bone marrow,compromising of normal hematopoi.esis and ultimately resulting in bone marrow failure.Chemotherapy is the mainstay treatment for all AML patients,however,drug resistance and clinical relapse limits its efficacy.The 5-year survival rate of AML patients is only 26.6%.Survival rates are even lower among patients ages 65 to 74 years(5.3%) and 75 years or older(1.6%).Therefore,exploring novel therapeutic agents is urgent for improving the outcome of patients with AML.Saponins are amphipathic glycosides found in traditional Chinese medicines.In the present study,we isolated a panel of saponins from Paris forrestii(Takht.) H.Li,a unique plant found in Tibet and Yunnan provinces,China.By examining their activities in suppressing acute myeloid leukemia cell proliferation,total saponins from Paris forrestii(TSPf) displayed more potent activity than individual ones.TSPf induced more than 40% AML cell apoptosis within 24 h and decreased the viability of all leukemia cell lines.TSPf-induced apoptosis was confirmed by both Annexin V staining and caspase-3 activation.TSPf downregulated pro-survival proteins Mcl-1,Bcl-xL and Bcl-2,but upreg.ulated the expression of tumor suppressor proteins p53,p27,Bax and Beclin 1.The AKT/mTOR signaling pathway is frequently over activated in various AML cells,and TSPf was found to suppress the activa.tion of both AKT and mTOR,but had no effects on their total protein expression.This was further con.firmed by the inactivation of 4 EBP-1 and p70 S6 K,two typical downstream signal molecules in the AKT/mTOR pathway.More specifically,TSPf-inactivated AKT/mTOR signaling was found to be associated with downregulated RNF6,a recently identified oncogene in AML.RNF6 activated AKT/mTOR,and consistently,knockdown of RNF6 led to inactivation of the AKT/mTOR pathway.Furthermore,TSPf suppressed the growth of AML xenografts in nude mice models.Oral administration of 100 mg · kg^(-1) body weight almost fully suppressed tumor growth within 14 d,without gross toxicity.This study thus demonstrated that TSPf displays potent anti-AML activity by suppressing the RNF6/AKT/mTOR pathway.Given its low toxicity,TSPf could be developed for the treatment of AML.
基金supported by Key Research and Development Program of Jiangsu Province(No.BE2019652)National Natural Science Foundation of China(81922025,81974388,82171461,81771457).
文摘Dear Editor,R-spondin3(RSPO3)is essential for vascular development and angiogenesis.Analyzing RSPO3-knockout embryos revealed severe vascular defects in the placenta(Aoki et al.2007).In both Xenopus and murine embryos,RSPO3 KO led to significant vascular defects(Kazanskaya et al.2008)and embryonic death(Kazanskaya et al.2008).In the placenta,RSPO3 could promote vascular endothelial growth factor(VEGF)expression(Kazanskaya et al.2008).RSPO3 is a ligand of low-density lipoprotein receptor-related protein 6(LRP6)and leucine-rich repeat G protein-coupled receptor 4(LGR4)to form a multiple ligands-receptors-cluster with Wnt and frizzled(FzD),thereby activating and amplifying downstreamβ-catenin signaling(in and Yoon 2012;Tocci et al.2020).
基金supported by grants from the National Natural Science Foundation of China(No.81803116 and No.32001072)Open Project Fund from NHC Key Laboratory of Male Reproductive Health/National Research Institute for Family Planning(2022GJP0102)+1 种基金Non-profit Central Research Institute Fund of National Research Institute For Family Planing(2022GJM02)Start-up Fund(Q410800320)from Soochow University.
文摘Approximately 31%of patients with 22q11.2 deletion syndrome(22q11.2DS)have genitourinary system disorders and 6%of them have undescended testes.Haploinsufficiency of genes on chromosome 22q11.2 might contribute to the risk of 22q11.2DS.In this study,we used mice with single-allele deletion in mitochondrial ribosomal protein L4o(Mrpl40-)as models to investigate the function of Mrpl40 in testes and spermatozoa development.The penetrance of cryptorchidism in Mrpl40+-mice was found to be higher than that in wild-type(WT)counterparts.Although the weight of testes was not significantly different between the WT and Mrpl40+-mice,the structure of seminiferous tubules and mitochondrial morphology was altered in the Mrpl40+-mice.Moreover,the concentration and motility of spermatozoa were significantly decreased in the Mrpl4O+-mice.In addition,data-independent acquisition mass spectrometry indicated that the expression of genes associated with male infertility was altered in Mrpl40+-testes.Our study demonstrated the important role of Mrpl40 in testicular structure and spermatozoa motility and count.These findings suggest that Mrpl4o is potentially a novel therapeutic target for cryptorchidism and decreased motility and count of spermatozoa.
基金This work was supported by the National Natural Science Foundation of China(31500802,82172132,and 82000523)the Natural Science Foundation of Jiangsu Province(BK20190097 and BK20190053)+2 种基金the Program of Qilu Young Scholars of Shandong UniversityThis work was also supported by the Cyrus Tang Foundation,the Taishan Scholars Program for Young Expert of Shandong Province(tsqn201909021)the Youth Cross-Scientific Innovation Group of Shandong University.
文摘Sepsis is a life-threatening organ dysfunction characterized by severe systemic inflammatory response to infection.Effective treatment of bacterial sepsis remains a paramount clinical challenge,due to its astonishingly rapid progression and the prevalence of bacterial drug resistance.
基金Supported by the Suzhou Municipal Developing Plan of Sciences and Technology(Social Development and Three-drug Keystone,No.SS0528)
文摘Objective:To observe the effect of electro-acupuncture(EA)on tumor necrosis factor-α(TNF-α) and vascular endothelial growth factor(VEGF)in peripheral blood and joint synovia in patients with rheumatoid arthritis(RA)to verify the clinical efficacy of EA.Methods:Adopting randomized controlled principle,the 63 RA patients enrolled were assigned to two groups,the 32 patients in the EA group were treated with EA,and the 31 patients in the simple needling(SN)group treated with simple needling.According to the integral-local combining method,the acupoints were selected mainly from yang-meridian and local Ashi points(pain-point).EA or SN was applied every other day,10 times as a course,and each patient received a total of 3 courses of treatment. Results:Blood and synovial levels of TNF-αand VEGF were reduced significantly after treatment in both groups.The lowering(absolute value and difference value)of TNF-αas well as the absolute value of VEGF, either in blood or in synovia,were similar in the two groups(P0.05);but the lowering of VEGF after treatment was more significant in the EA group than that in the SN group(P0.05).Conclusion:EA could effectively lower the contents of TNF-αand VEGF in peripheral blood and joint synovia to improve the internal environment for genesis and development of RA,so as to enhance the clinical therapeutic effectiveness.
文摘In the present study, three new triterpenoids, 23-hydroxyurs-12, 18-dien-28-oic acid 3β-O-α-L-arabinopyranoside(1), 23-hydroxyurs-12, 18-dien-28-oic acid 3β-O-β-D-glucuronopyranoside-6-O-methyl ester(2), and urs-12, 18-dien-28-oic acid 3β-O-β-D-glucuronopyranoside-6-O-methyl ester(3), and a known triterpenoid, 3β-hydroxy-urs-2, 18-dien-28-oic acid(4, randialic acid B), were isolated from the aerial parts of Ilex cornuta. Their structures were identified by the spectroscopic analyses(IR, ESI-MS, HR-ESI-MS, and 1D and 2D NMR) and chemical reactions. Compound 4 showed significant cell-protective effects against H_2O_2-induced H9c2 cardiomyocyte injury. Compounds 1-4 did not show any significant DPPH radical scavenging activity.
基金This study is funded by Zhejiang Basic Public Welfare Research Project(LGF19H100002).
文摘Background Macrophage activation syndrome(MAS)is a major cause of morbidity and mortality in pediatric rheumatology.We aimed to further understand the clinical features,treatment,and outcome of MAS in China.Methods A multi-center cohort study was performed in seven hospitals in China from 2012 to 2018.Eighty patients with MAS were enrolled,including 53 cases with systemic juvenile idiopathic arthritis(SJIA-MAS),10 cases of Kawasaki disease(KD-MAS),and 17 cases of connective tissue disease(CTD-MAS).The clinical and laboratory data were collected before(pre-),at onset,and during full-blown stages of MAS.We compared the data among the SJIA-MAS,KD-MAS,and CTD-MAS subjects.Results 51.2%of patients developed MAS when the underlying disease was first diagnosed.In patients with SJIA,22.6%(12/53)were found to have hypotension before the onset of SJIA-MAS.These patients were also found to have significantly increased aspartate aminotransferase(AST)and lactate dehydrogenase(LDH),as well as decreased albumin(P<0.05),but no difference in alanine aminotransferase,ferdtin,and ratio of ferritin/erythrocyte sedimentation rate(ESR)at onset of MAS when compared to pre-MAS stages of the disease.In addition,ferritin and ratio of ferritin/ESR were significantly elevated in patients at full-blown stages of SJIA-MAS compared to pre-MAS stage.Significantly increased ferritin and ratio of ferritin/ESR were also observed in patients with SJIA compared to in KD and CTD.Receiver-operating characteristic analysis showed that 12,217.5μg/L of ferritin and 267.5 of ferritin/ESR ratio had sensitivity(80.0%and 90.5%)and specificity(88.2%and 86.7%),respectively,for predicting full-blown SJIA-MAS.The majority of the patients received corticosteroids(79/80),while biologic agents were used in 12.5%(10/80)of cases.Tocilizumab was the most commonly selected biologic agent.The overall mortality rate was 7.5%.Conclusions About half of MAS occurred when the underlying autoimmune diseases(SJIA,KD,and CTD)were first diagnosed.Hypotension could be an important manifestation before MAS diagnosis.Decreased albumin and increased AST,LDH,ferritin,and ratio of ferritin/ESR could predict the onset or full blown of MAS in patient with SJIA.
文摘Background Acute hypoxemic respiratory failure (AHRF) often develops acute respiratory distress syndrome (ARDS), and its incidence and mortalities in critically ill pediatric patients in China were 2% and 40% respectively. This study aimed at prospectively investigating incidence, causes, mortality and its risk factors, and any relationship to initial tidal volume (VT) levels of mechanical ventilation, in children 〈5 years of age with AHRF and ARDS. Methods In 12 consecutive months in 23 pediatric intensive care units (PICU), AHRF and ARDS were identified in those requiring 〉12 hour intratracheal mechanical ventilation and followed up for 90 days or until death or discharge. ARDS was diagnosed according to the American-European Consensus definitions. The mortality and ventilation free days (VFD) were measured as the primary outcome, and major complications, initial disease severity, and burden were measured as the secondary outcome. Results In 13 491 PICU admissions, there were 439 AHRF, of which 345 (78.6%) developed ARDS, resulting in incidences of 3.3% and 2.6%, and corresponding mortalities of 30.3% and 32.8% respectively along with 8.2 and 6.7 times of relative risk of death in those with pneumonia (62.9%) and sepsis (33.7%) as major underlying diseases respectively. No association was found in VT levels during the first 7 days with mortality, nor for V-r at levels 〈6, 6-8, 8-10, and 〉10 ml/kg in the first 3 days with mortality or length of VFD. By binary Logistic regression analyses, higher pediatric risk of mortality score III, higher initial oxygenation index, and age 〈1 year were associated with higher mortality or shorter VFD in AHRF. Conclusions The incidence and mortalities of AHRF and ARDS in children 〈5 years were similar to or lower than the previously reported rates (in age up to 15 years), associated with initial disease severity and other confounders, but causal relationship for the initial VT levels as the independent factor to the major outcome was not found.
基金supported by the grants from the National Natural Science Foundation of China(Nos.81870365,81971477 and 81970436)the National Youth Foundation of China(No.81800437)+1 种基金the Jiangsu Provincial Medical Young Talents(QNRC2016756 and QNRC2016764)the Shanghai Science and Technology Support Project for Medicine(No.18411967300).
文摘Background The aim of this study is to explore the characteristics of Kawasaki disease(KD)and concurrent pathogens due to a stay-at-home isolation policy during coronavirus disease 2019(COVID-19)epidemic.Methods All patients with KD admitted between February and April in 2015-2020,were classified into before(group 1,in 2015-2019)and after(group 2,in 2020)isolation groups.A total of 4742 patients[with KD(m=98)and non-KD(n=4644)]referred to Mycoplasma pneumoniae(MP)and virus detection were analyzed in 2020.Clinical characteristics,laboratory data,and 13 pathogens were analyzed retrospectively.Results Group 2 had a significantly increased incidence of KD(0.11%)with 107 patients compared to that of group 1(0.03%)with 493 patients.The comparisons of oral mucosal change,strawberry tongue,desquamation of the fingertips,cervical lymphadenopathy and neutrophil percentage decreased in group 2 compared to group 1.The infection rate of MP increased significantly in group 2(34.7%)compared to group 1(19.3%),while the positive rate of viruses decreased significantly in group 2(5.3%)compared to group 1(14.3%).In 2020,the positive rate of MP infection increased significantly in patients with KD compared to the increase in patients with non-KD.The infection rate of MP for younger children aged less than 3 years old was higher in group 2 than in group 1.Conclusion Compared with the characteristics of KD from 2015 to 2019 years,the incidence of KD was increased in 2020 and was accompanied by a high incidence of MP infection,especially in younger children(less than 3 years old)during the isolation due to COVID-19 pandemic.
文摘Background Glucocorticoid receptor (GR) is believed to be a major factor in brain maturation and in modulation of a series of brain activity. Hippocampal neurons are abundant in glucocorticoid receptor, and there is significant change in GR expression under certain pathological state. Epilepsy is a special pathological state of the central nervous system. This study aimed to explore the role of GR in epilepsy by observing the change and functions of GR in hippocampus with a basolateral amygdale-electrical kindled rat epilepsy model. Methods Firstly, we established the basolateral amygdale-electrical kindled rat epilepsy model. Then GR mRNA expression in the hippocampus was assayed by semi-quantitative reverse transcription-PCR in this experiment. In addition, the processes of epileptic seizures were observed and electroencephalograms were recorded. One-way analysis of variance (ANOVA) was employed for comparing means of multiple groups, followed Fisher's least significant difference (LSD) for paired comparison. Results The rats were successfully kindled after an average of (13.50+3.99) times electrical stimulation, in which it was showed that GR mRNA expression reduced obviously as compared with the control group and the sham groups (P 〈0.001). The down-regulation of GR mRNA expression was abated or reversed by some anti-epilepsy drugs (P 〈0.001 compared with the epilepsy group), accompanied by attenuation of seizures and improvement of electroencephalograms. Conclusions Down-regulation of hippocampal GR mRNA expression may be related to the kindling. Anti-epilepsy drugs exposure can retard this change.