The Viral Load of Epstein-Barr Virus in Blood of Children after Hematopoietic Stem Cell Transplantation

Objective To detect the Epstein-Barr virus(EBV)viral load of children after hematopoietic stem cell transplantation(HSCT)using chip digital PCR(cdPCR).Methods The sensitivity of cdPCR was determined using EBV plasmids and the EBV B95-8 strain.The specificity of EBV cdPCR was evaluated using the EBV B95-8 strain and other herpesviruses(herpes simplex virus 1,herpes simplex virus 2,varicella zoster virus,human cytomegalovirus,human herpesvirus 6,and human herpesvirus 7).From May 2019 to September 2020,64 serum samples of children following HSCT were collected.EBV infection and the viral load of serum samples were detected by cdPCR.The epidemiological characteristics of EBV infections were analyzed in HSCT patients.Results The limit of detection of EBV cdPCR was 110 copies/mL,and the limit of detection of EBV quantitative PCR was 327 copies/mL for the pUC57-BALF5 plasmid.The result of EBV cdPCR was up to 121 copies/mL in the EBV B95-8 strain,and both were more sensitive than that of quantitative PCR.Using cdPCR,the incidence of EBV infection was 18.75%in 64 children after HSCT.The minimum EBV viral load was 140 copies/mL,and the maximum viral load was 3,209 copies/mL using cdPCR.The average hospital stay of children with EBV infection(184±91 days)was longer than that of children without EBV infection(125±79 days),P=0.026.Conclusion EBV cdPCR had good sensitivity and specificity.The incidence of EBV infection was 18.75%in 64 children after HSCT from May 2019 to September 2020.EBV cdPCR could therefore be a novel method to detect EBV viral load in children after HSCT.

Pathogenic changes of community-acquired pneumonia in a children’s hospital in Beijing,China before and after COVID-19 onset:a retrospective study

Background This study aimed to analyze the pathogenic characteristics of community-acquired pneumonia(CAP)in a children’s hospital before and after the coronavirus disease 2019(COVID-19)pandemic and to provide testimony for preventing CAP in the future.Methods A retrospective analysis was performed.The information was collected from the electronic medical record system of the hospital.A total of 2739 children were included from February 1,2019,to January 31,2021.Results Among these 2739 patients were 1507(55.02%)males and 1232(44.98%)females;the median age was 3.84 years.There were 2364 cases during the pre-COVID-19 period and 375 cases during the post-COVID-19 period.The number of hospitalized children after the pandemic was 84.14%lower.The median age after the onset was 1.5 years younger than that before the onset(4.08 years old)(Z=−7.885,P<0.001).After the pandemic,the proportion of CAP in school-age children and Mycoplasma pneumoniae pneumonia(MPP)and influenza virus pneumonia(IVP)decreased significantly.During the pre-COVID-19 period,the proportions of detected pathogens were as follows:MP(59.56%)>bacteria(50.42%)>viruses(29.57%)>fungi(3.43%).During the post-COVID-19 period,the pathogen proportions were bacteria(56.53%)>viruses(53.60%)>MP(23.47%)>fungi(3.73%).Conclusions There was a significant decrease in the number of children with CAP hospitalized after the pandemic,especially among school-age children,and the pathogen proportions of CAP with MP and IV were significantly decreased.We inferred that CAP was effectively prevented in school-age children because of the strong mitigation measures.

Y-splitting medial rectus muscle and recession in treatment for convergence excess esotropia

AIM: To evaluate the surgical outcome of medial rectus(MR) recession with Y-splitting procedure in treatment of esotropia with convergence excess.METHODS: Medical records were retrospectively reviewed for those patients who underwent surgical treatment for their convergence excess esotropia(CEET) between January 2018 and December 2020. Refractive error was examined by the equipment of the VS100(Welch Allyn). The surgical approach was bilateral MR recession with Y-splitting. The amount of recession was calculated according to the deviation angle at distance. Ocular movement and ocular alignment at distance and near were evaluated pre-and post-operatively. Binocular sensory status was evaluated by the Bagolini striated glasses at near and distance, and by stereoacuity assessment at near using the Titmus test.RESULTS: Six patients with CEET were included in this study. Four of them were hyperopia and two of them were myopia. A mean of eso-deviation angle at distance had been changed from 27.3±13.02 prism diopters(PD) preoperatively to 1.83±1.60 PD postoperatively(P<0.05), while a mean of eso-deviation angle at near had been changed from 50.00±20.74 PD preoperatively to 6.83±0.98 PD postoperatively(P<0.05). Patients had obtained binocular vision postoperatively.CONCLUSION: The surgical approach of Y-splitting MR and recession is effective in treatment of CEET.

Endoscopy-assisted purely total outer wall excision for pediatric Sylvian arachnoid cysts

Background To present a novel endoscopy-assisted surgical strategy of Sylvian arachnoid cysts(ACs).Case presentation Endoscopy-assisted surgery was performed on 9 children(May 2019-December 2021).All patients were evaluated with CT and/or MRI and had regular follow-up examinations.The procedure consisted of performing a small temporal craniotomy(2 cm)behind the hairline.After dural opening,the surgery was performed with the assistance of a rigid 30-degree transcranial endoscope,self-irrigating bipolar forceps,and other standard endoscopic instruments.Steps included total excision of the AC outer wall and dissection of arachnoid adhesion around the cystic edge to communicate the residual cyst cavity with subdural space.Compared with the microscopical procedure,a 30-degree transcranial endoscope provides a wider view,especially for the lateral part exposure of the outer wall.The average age of the patients was 27.7 months(range 13-44 months).The Sylvian AC was in the right hemisphere in three patients and six in the left,respectively.1 patient suffered transient postoperative epilepsy.There was no mortality or additional postoperative neurological deficit in this series.All of the patients achieved significant clinical improvement after surgery.Radiological examination after the operation showed a significant reduction in all cases(100%,9/9)and disappearance in one case(11.1%,1/9).Postoperative subdural fluid collection occurred in six cases and completely resolved spontaneously in 9 months.Conclusion The study demonstrated the minimally invasive,safety,and effectivity of the endoscopy-assisted purely total outer wall excision.

Single-cell transcriptomic analysis reveals a systemic immune dysregulation in COVID-19-associated pediatric encephalopathy

Unraveling the molecular mechanisms for COVID-19-associated encephalopathy and its immunopathology is crucial for developing effective treatments.Here,we utilized single-cell transcriptomic analysis and integrated clinical observations and laboratory examination to dissect the host immune responses and reveal pathological mechanisms in COVID-19-associated pediatric encephalopathy.We found that lymphopenia was a prominent characteristic of immune perturbation in COVID-19 patients with encephalopathy,especially those with acute necrotizing encephalopathy(AE).This was characterized a marked reduction of various lymphocytes(e.g.,CD8^(+)T and CD4^(+)T cells)and significant increases in other inflammatory cells(e.g.,monocytes).Further analysis revealed activation of multiple cell apoptosis pathways(e.g.,granzyme/perforin-,FAS-and TNF-induced apoptosis)may be responsible for lymphopenia.A systemic S100A12 upregulation,primarily from classical monocytes,may have contributed to cytokine storms in patients with AE.A dysregulated type I interferon(IFN)response was observed which may have further exacerbated the S100A12-driven inflammation in patients with AE.In COVID-19 patients with AE,myeloid cells(e.g.,monocytic myeloid-derived suppressor cells)were the likely contributors to immune paralysis.Finally,the immune landscape in COVID-19 patients with encephalopathy,especially for AE,were also characterized by NK and T cells with widespread exhaustion,higher cytotoxic scores and inflammatory response as well as a dysregulated B cell-mediated humoral immune response.Taken together,this comprehensive data provides a detailed resource for elucidating immunopathogenesis and will aid development of effective COVID-19-associated pediatric encephalopathy treatments,especially for those with AE.

Consensus for criteria of running a pediatric inflammatory bowel disease center using a modified Delphi approach

Background Good quality of care for inflammatory bowel disease(IBD)depends on high-standard management and facility in the IBD center.Yet,there are no clear measures or criteria for evaluating pediatric IBD(PIBD)center in China.The aim of this study was to develop a comprehensive set of quality indicators(QIs)for evaluating PIBD center in China.Methods A modified Delphi consensus-based approach was used to identify a set of QIs of structure,process,and outcomes for defining the criteria.The process included an exhaustive search using complementary approaches to identify potential QIs,and two web-based voting rounds to select the QIs defining the criteria for PIBD center.Results A total of 101 QIs(35 structures,48 processes and 18 outcomes)were included in this consensus.Structure QIs focused on the composition of multidisciplinary team,facilities and services that PIBD center should provide.Process QIs highlight core requirements in diagnosing,evaluating,treating PIBD,and disease follow-up.Outcome QIs mainly included criteria evaluating effectiveness of various interventions in PIBD centers.Conclusion The present Delphi consensus developed a set of main QIs that may be useful for managing a PIBD center.

DCX and CRABP2 are candidate genes for differential diagnosis between pre-chemotherapy embryonic and alveolar rhabdomyosarcoma in pediatric patients

Importance Rhabdomyosarcoma(RMS)is the most common soft tissue sarcoma in children.More than 90%of cases are classified as embryonic RMS(ERMS)or alveolar RMS(ARMS).ERMS has a worse prognosis than ARMS.Early differential diagnosis is of paramount importance for optimization of treatment.Objective To identify genes that are differentially expressed between ARMS and ERMS,which can be used for accurate rhabdomyosarcoma classification.Methods Three Gene Expression Omnibus datasets composed of ARMS and ERMS samples were screened and 35 differentially expressed genes(DEGs)were identified.Receiver operating characteristic curve analysis and area under the curve analysis was performed for these 35 DEGs and seven candidate genes with the best differential expression scores between ARMS and ERMS were determined.The expression of these seven candidate genes was validated by immunohistochemical analysis of pre-chemotherapy ARMS and ERMS specimens.Results The levels of DCX and CRABP2 were confirmed to be remarkably different between paraffin-embedded ARMS and ERMS tissues,while EGFR abundance was only marginally different between these two RMS subtypes.Interpretation DCX and CRABP2 are potential biomarkers for distinguishing ARMS from ERMS in pre-chemotherapy pediatric patients.

Application of Human Adenovirus Genotyping by Phylogenetic Analysis in an Outbreak to Identify Nosocomial Infection

Nosocomial infections are common in pediatric patients and can be fatal in infants and immunocompromised patients. In September 2018, a high positive rate of human adenovirus HAdV was occurred among hospitalized children in the Children's Hospital Affiliated to the Capital Institute of Paediatrics in Beijing. To investigate whether this outbreak of HAdV was related to nosocomial infections or the result of community infections, we collected respiratory specimens from patients with acute respiratory infections in a respiratory ward during June to December 2018, and screened for respiratory viruses. Among 1,840 cases included, 95(5.2%, 95/1840) were positive for HAdV and 81 were genotyped based on phylogenetic analysis, including seven as HAdV-1(8.6%), 30 HAdV-3(37.0%), two HAdV-6(2.5%), and 42 HAdV-7(51.9%). More HAdV-positive samples were collected in August(4.7%, 12/255), September(15.0%, 41/274) and October(6.9%, 17/247), with a peak in September 2018. By combining the results of HAdV phylogenetic analysis with clinical data of patients, there were 77 cases(4.2%, 77/1840;81.1%, 77/95) excluded from nosocomial infections, eight cases representing possible infections transmitted by visitors or attending parents, three cases without sequences that might have been due to infection transmitted by roommates positive for HAdV, one case of a roommate without an HAdV sequence, and six cases that shared highly homologous sequences with those of their roommates, for which nosocomial infections might be considered. In conclusion, genotyping of HAdVs based on phylogenetic analysis combined with clinical information provides a powerful method to distinguish nosocomial infections from community acquired infection, especially when tracing the origins of nosocomial infections.

Prevention of Deep Vein Thrombosis by Panax Notoginseng Saponins Combined with Low-Molecular-Weight Heparin in Surgical Patients

Objective:To evaluate the efficacy of deep vein thrombosis(DVT)prevention among realworld surgical inpatients who received panax notoginseng saponins(PNS)combined with low-molecularweight heparin(LMWH).Methods:A prospective cohort study was conducted among surgical patients between January 2016 and November 2018 in Xuanwu Hospital,Capital Medical University,Beijing,China.Participants received LMWH alone or PNS combined with LMWH for preventing DVT.The primary outcome was incidence of lower extremity DVT,which was screened once a week.Participants in the LMWH group were given LMWH(enoxaparin)via hypodermic injection,4000-8000 AxalU once daily.Participants in the exposure group received PNS(Xuesaitong oral tablets,100 mg,3 times daily)combined with LMWH given the same as LMWH group.Results:Of the 325 patients screened for the study,281 participants were included in the final analysis.The cohort was divided into PNS+LMWH group and LMWH group with 134 and 147 participants,respectively.There was a significant difference of DVT incidence between two groups(P=0.01),with 21(15.7%)incident DVT in the PNS+LMWH group,and 41(27.9%)incident DVT in the LMWH group.Compared with participants without DVT,the participants diagnosed with DVT were older and had higher D-dimer level.The multivariate logistic regression moclel showed a significant lower risk of incident DVT among participants in the PNS+LMWH group compared with the LMWH group(odds ratio 0.46,95%confidence interval,0.25-0.86).There were no significant differences in thromboelaslography values(including R,K,Angle,and MA)and differences in severe bleeding between two groups.No symptomatic pulmonary embolism occurred during the study.Conclusion:Combined application of PNS and LMWH can effectively reduce the incidence of DVT among surgical inpatients compared with LMWH monotherapy,without increased risk of bleeding.

The cell cycle inhibitor P21 promotes the development of pulmonary fibrosis by suppressing lung alveolar regeneration

The cell cycle inhibitor P21 has been implicated in cell senescence and plays an important role in the injury-repair process following lung injury.Pulmonary fibrosis(PF)is a fibrotic lung disorder characterized by cell senescence in lung alveolar epithelial cells.In this study,we report that P21 expression was increased in alveolar epithelial type 2 cells(AEC2 s)in a time-dependent manner following multiple bleomycin-induced PF.Repeated injury of AEC2 s resulted in telomere shortening and triggered P21-dependent cell senescence.AEC2 s with elevated expression of P21 lost their self-renewal and differentiation abilities.In particular,elevated P21 not only induced cell cycle arrest in AEC2 s but also bound to P300 andβ-catenin and inhibited AEC2 differentiation by disturbing the P300-β-catenin interaction.Meanwhile,senescent AEC2 s triggered myofibroblast activation by releasing profibrotic cytokines.Knockdown of P21 restored AEC2-mediated lung alveolar regeneration in mice with chronic PF.The results of our study reveal a mechanism of P21-mediated lung regeneration failure during PF development,which suggests a potential strategy for the treatment of fibrotic lung diseases.

Disease characteristics and neuropathological changes associated with cognitive dysfunction in obstructive sleep apnea

Obstructive sleep apnea(OSA)is a common sleep-disordered breathing disease that often leads to many comorbidities(e.g.,cognitive dysfunction),which adversely affect the quality of life for patients with OSA.Thus far,the underlying mechanisms of this dysfunction remain unclear.Many studies have focused on OSA-related characteristics,including intermittent hypoxemia and sleep fragmentation.There is increasing emphasis on neuroimaging studies to explore underlying relationships between neuropathological changes and cognitive dysfunction.This article reviews recent research progress concerning cognitive dysfunction associated with OSA to reveal potential mechanisms that contribute to this dysfunction.

Chemokine CCL1 as a therapeutic target for pulmonary fibrosis: comments on ‘The chemokine CCL1 triggers an AMFR‒SPRY1 pathway that promotes differentiation of lung fibroblasts into myofibroblasts and drives pulmonary fibrosis’

Pulmonary fibrosis(PF)is a type of chronic and progressive respiratory diseases characterized by excessive extracellular matrix(ECM)deposition,interstitial fibrotic lesions,and architectural distortion.Patients with PF suffer from pulmonary function decline and progressive worsening of dyspnea with poor prognosis(Wilson and Wynn,2009).Although recent progress provides mechanistic insights into the pathogenesis of PF,no effective treatment against PF is available other than lung transplantation.Therefore,a better understanding of the molecular and cellular mechanisms of PF is crucial for the discovery of new therapeutic targets for safe and effective anti-PF drugs.

Ex utero intrapartum therapy in infants with congenital diaphragmatic hernia:a propensity score matching analysis

Objective Previous studies have shown that ex utero intrapartum therapy(EXIT)is safe and feasible for newborns with congenital diaphragmatic hernia(CDH).This study reports our experience with EXIT in fetuses with CDH in an attempt to explore the efficacy of EXIT on the survival rate of this population.Methods A retrospective analysis of the clinical data of 116 children with CDH was conducted.The children were assigned to EXIT and non-EXIT groups.Propensity score matching(PSM)toward clinical data was performed,and the clinical characteristics and outcomes were compared.Taking survival at discharge as the main outcome,logistic regression analysis was carried out to explore the efficacy of EXIT on survival.Results During the study period,30 of 116 children received EXIT.After PSM,the survival rates of the EXIT group and the non-EXIT group were 82.76%(24/29)and 48.28%(14/29),respectively(p=0.006).EXIT(OR=0.083,95%CI=0.013to 0.525,p=0.008),liver herniation(OR=16.955,95%CI=2.342 to 122.767,p=0.005),and gestational age at diagnosis(OR=0.662,95%CI=0.497 to 0.881,p=0.005)were independent mortality-related risk factors of all children with CDH.Ninety-nine of 116 children underwent surgery.After PSM,the postoperative survival rates of the EXIT group and non-EXIT group were 84.6%(22/26)and 76.9%(20/26),respectively(p=0.754).Liver herniation(OR=10.451,95%CI=1.641 to 66.544,p=0.013)and gestational age at diagnosis(OR=0.736,95%CI=0.577 to 0.938,p=0.013)were independent mortality-related risk factors of children after surgery.Conclusion EXIT can be performed safely for selected prenatally diagnosed CDH neonates with potentially better survival and does not cause more maternal complications compared with traditional cesarean section.

两例无关的罕见I型Crigler-Najjar综合征患者:两种新突变和一例患者UGT1A1基因杂合性缺失(英文)

研究目的:I型Crigler-Najjar综合征(CN-I)为先天性间接胆红素血症的最严重的一种,是由位于染色体2q37的葡萄糖醛酸转移酶基因(UGT1A1)的纯合或复合杂合突变引起的一种罕见的遗传性疾病。本研究对来自两个无关家庭的两例临床诊断为CN-I的患儿及父母进行UGT1A1基因分子遗传学分析。研究方法:经知情同意后,采集两例患儿及父母外周血;聚合酶链式反应(PCR)扩增UGT1A1基因5个外显子及外显子-内含子交界处,进行测序分析。应用实时定量PCR(qRT-PCR)测定其中一例患者UGT1A1基因的拷贝数。重要结论:本研究在两例CN-I型患儿中检测到3个UGT1A1基因突变:c.239_245delCTGTGCC(p.Pro80HisfsX6)、c.1253delT(p.Met418ArgfsX5)和c.1156G>T(p.Val386Phe)。前两个突变均为新发的移码突变,预测提前出现终止密码或诱发RNA降解;而突变c.1156G>T(p.Val386Phe)的致病机制尚需进一步研究。