2017 Chinese expert consensus on the clinical application ofserum marker for thyroid cancer

In recent years, the clinical incidence of thyroid cancer has been increasing year by year, and its risk assessment and clinical management methods have also been accordingly modified and constantly improved. There are great differences between the clinical diagnostic and therapeutic modes and disease management of thyroid cancer employed by various medical institutions in China, particularly with regard to the clinical application of serum marker of thyroid cancer. To this end, the China Anti-Cancer Association Thyroid Cancer Specialized Committee Chinese Association of Thyroid Oncology organized this compilation of ExpertConsensus on Clinical Application of Serum Marker of Thyroid Cancer to help and impel relevant clinical institutions and professionals to standardize clinical diagnosis, treatment, and long-term management of thyroid cancer, and to properly utilize the serum marker for scientific auxiliary clinical diagnosis and assessment of thyroid cancer before and after operation.

2016 Chinese expert consensus and guidelines for the diagnosis and treatment of papillary thyroid microcarcinoma

The incidence of papillary thyroid carcinoma(PTC)has exponentially increased in recent years.Papillary thyroid microcarcinoma(PTMC)accounts for the majority of the reported cases of PTC.The debates and crucial issues in PTMC management have received researchers'attention.To further improve the clinical management of PTMC in China,

Broadband Sheet Parametric Oscillator for x^((2)) Optical Frequency Comb Generation via Cavity Phase Matching

We demonstrate a broadband optical parametric oscillation,using a sheet cavity,via cavity phase-matching.A21.2 THz broad comb-like spectrum is achieved,with a uniform line spacing of 133.0 GHz,despite a relatively large dispersion of 275.4 fs^(2)/mm around 1064 nm.With 22.6% high slope efficiency,and 14.9 kW peak power handling,this sheet optical parametric oscillator can be further developed for x^((2)) comb.

Newborn screening with targeted sequencing:a multicenter investigation and a pilot clinical study in China

Different newborn screening(NBS) programs have been practiced in many countries since the 1960 s. It is of considerable interest whether next-generation sequencing is applicable in NBS. We have developed a panel of 465 causative genes for 596 early-onset, relatively high incidence, and potentially actionable severe inherited diseases in our Newborn Screening with Targeted Sequencing(NESTS) program to screen 11,484 babies in 8 Women and Children’s hospitals nationwide in China retrospectively. The positive rate from preliminary screening of NESTS was 7.85%(902/11,484). With 45.89%(414/902) follow-up of preliminary positive cases, the overall clinically confirmative diagnosis rate of monogenic disorders was 12.07%(50/414), estimating an average of 0.95%(7.85% × 12.07%) clinical diagnosis rate, suggesting that monogenic disorders account for a considerable proportion of birth defects. The disease/gene spectrum varied in different regions of China. NESTS was implemented in a hospital by screening 3923 newborns to evaluate its clinical application. The turn-around time of a primary report, including the sequencing period of < 7 days, was within 11 days by our automatic interpretation pipeline. Our results suggest that NESTS is feasible and cost-effective as a first-tier NBS program, which will change the status of current clinical practice of NBS in China.

Pneumomediastinum Secondary to Foreign Body Aspiration： Clinical Features and Treatment Explorement in 39 Pediatric Patients

Background：Pneumomediastinum （PM） secondary to foreign body aspiration （FBA） is rare in children.Although it is mainly benign,some cases may be fatal.Due to the rare nature of this clinical entity,proper assessment and management have been poorly studied so far.Here,we characterized the presentation and management of this clinical entity and provided an evaluation system for the management.Methods：We retrospectively reviewed children with PM secondary to FBA,who were treated in Beijing Children＇s Hospital from January 2010 to December 2015.All patients were stratified according to the degree of dyspnea on admission,and interventions were given accordingly.Bronchoscopic removals of airway foreign bodies （FBs） were performed on all patients.For patients in acute respiratory distress,emergent air evacuation and/or resuscitations were performed first.Admission data,interventions,and clinical outcomes were recorded.Results：A total of 39 patients were included in this study.The clinical severity was divided into three grades （Grades Ⅰ,Ⅱ,and Ⅲ） according to the degree of dyspnea.Thirty-one patients were in Grade Ⅰ dyspnea,and they simply underwent bronchoscopic FBs removals.PM resolved spontaneously and all patients recovered uneventfully.Six patients were in Grade Ⅱ dyspnea,and emergent drainage preceded rigid bronchoscopy.They all recovered uneventfully under close observation.Two exhausted patients were in Grade Ⅲ dyspnea.They died from large PM and bilateral pneumothorax,respectively,despite of aggressive interventions in our hospital.Conclusions：PM secondary to FBA could be life-threatening in some patients.The degree of dyspnea should be evaluated immediately,and patients in different dyspnea should be treated accordingly.For patients in Grade Ⅰ dyspnea,simple bronchoscopic FBs removals could promise a good outcome.For patients in Grade Ⅱ dyspnea,emergent air evacuation and/or resuscitation should precede a bronchoscopy before the children become exhausted.

2 μm optical frequency comb generation via optical parametric oscillation from a lithium niobate optical superlattice box resonator

Optical parametric oscillators(OPOs) can downconvert the pump laser to longer wavelengths with octave separation via χ^((2)), which is widely used for laser wavelength extension including mid-infrared(MIR) generation.Such a process can be integrated in monolithic resonators, being compact and low in threshold. In this work, we show that the monolithic χ^((2))mini-OPO can also be used for optical frequency comb generation around 2096 nm and enters the boundary of MIR range. A new geometry called an optical superlattice box resonator is developed for this realization with near-material-limited quality factor of 4.0 × 10^(7). Only a continuous-wave near-infrared pump laser is required, with OPO threshold of 80 mW and output power up to 340 mW. Revival temporal profiles are measured at a detectable repetition frequency of 1.426 GHz, and narrow beat note linewidth of less than 10 Hz shows high comb coherence. These results are in good agreement with our simulation for a stable comb generation. Such an OPO-based comb source is useful for carbon dioxide sensing or the mine prospect applications and can be generalized to longer MIR wavelengths for general gas spectroscopy.

A review of the risk factors associated with juvenile-onset recurrent respiratory papillomatosis:genetic,immune and clinical aspects

Background Juvenile-onset recurrent respiratory papillomatosis(JoRRP)is one of the most common benign lesions of hyperplastic respiratory epithelial tissue in children and is predominantly caused by human papillomaviruses(HPVs)6 and 11.The clinical course of the disease is variable,and some patients even develop a malignancy.The purpose of this review was to summarize the related factors affecting the disease course in patients with JoRRP.Data sources We used databases,including PubMed and Google Scholar,to search for publications on factors associated with the genetic,immune,and clinical aspects of JoRRP.The most relevant articles to the scope of this review were chosen for analysis.Results Mother-to-child transmission is the most important mode of disease transmission;other factors,such as immune condition or genetic susceptibility,may be important determinants of JoRRP occurrence.Genetically,the presence of DRBI*0301 and HFV 6/11 E6/E7 is associated with a more severe disease.Immunewise,patients have an enhanced T helper 2-like response.In addition,regulatory T cells are enriched in tumors and may become one of the effective prognostic indicators.For clinical characteristics,patients infected with HPV-11 have more aggressive disease.However,compared with HPV type,age at first onset is a more important factor related to the aggressiveness of JoRRP.Furthermore,socioeconomic status may also affect the course.Conclusions Genetic,immune,and some clinical factors have been noted to play an important role in the course of JoRRP.Exploring definite influencing factors will be an important direction of research in the future.

Correlation between TERT C228T and clinic-pathological features in pediatric papillary thyroid carcinoma

The aims of the present study were to reveal the prevalence of the TERT C228 T mutation in pediatric papillary thyroid carcinoma(PPTC) and to further investigate the role of the TERT C228 T mutation in PPTC. We also tested another TERT mutation, TERT C250 T, although this was not detected in PPTC patients. In this study, 48 patients with PPTC(41 with classic PPTC) were enrolled. DNA was extracted from PPTC tissues and TERT C228 T mutation analysis was performed. Chi-squared analysis,Fisher’s exact test, and a t-test were applied to test the significance of differences. The TERT C228 T mutation presented in 13(27.1%) of the 48 PPTC patients and 10(24.4%) of the 41 classical PPTC patients. There were significant differences between PPTC patients with the TERT C228 T mutation and those without in terms of modified radical neck dissection, multifocality,capsular invasion, extrathyroidal invasion, and American Joint Committee on Cancer(AJCC) tumor stage(P<0.05). In classical PPTC, there were additional significant differences in other clinic-pathological features, such as AJCC nodal stage(P=0.009)and American Thyroid Association(ATA) PPTC stage(P=0.021) between patients with and without the TERT C228 T mutation.These findings indicate that the TERT C228 T mutation is significantly correlated with certain aggressive clinic-pathological features of PPTC.

Correlation between BRAF^(V600E) mutation and clinicopathological features in pediatric papillary thyroid carcinoma

In adults, the presence of the BRAF^(V600E) mutation in papillary thyroid cancer(PTC) has been demonstrated to be strongly associated with aggressive cancer-cell characteristics and poor patient prognosis. In contrast, the frequency of this mutation in pediatric PTC has undergone limited study, and the few available estimates range from 0 to 63%. Furthermore, the role of the BRAF^(V600E) mutation in pediatric PTC is controversial; thus, the present study aimed to investigate the prevalence and role of the BRAF^(V600E) mutation in48 pediatric patients with PTC, aged 3–13 years. Of these patients, 41 were diagnosed with classic PTC, five were found to have a follicular variant of PTC, and two to exhibit a diffuse sclerosing PTC variant. The BRAF^(V600E) mutation was identified to be present in 35.4% of the 48 analyzed patients, and in 41.5% of the patients diagnosed with classical PTC. Furthermore, the presence of the BRAF^(V600E) mutation was found to be associated with a patient age at diagnosis of less than ten years(P=0.011), the performance of a thyroidectomy(P=0.03), exhibited tumor multifocality(P=0.02) and/or extra-thyroidal invasion(P=0.003), and both a low MACIS(Metastases, Age, Completeness of resection, Invasion, Size)(P=0.036) and AMES(Age, Metastasis, Extent of tumor,Size)(P=0.001)score. Together, these data suggest that the presence of the BRAF^(V600E) mutation may be negatively correlated with partial aggressive clinicopathological features of pediatric PTC.

Ambulatory blood pressure monitoring in children with obstructive sleep apnea syndrome

Importance:The incidence of obstructive sleep apnea syndrome(OSAS)in children has increased year by year recently.Blood pressure research of OSAS children can help understand the occurrence of OSAS related complications.Early detection and intervention of blood pressure changes in children with OSAS can reduce the incidence of cardiovascular disease in later adulthood.Objective:To investigate the differences in blood pressure among different groups of snoring children and different sleep stages.Methods:Habitually snoring children(snoring frequency of≥3 nights per week)aged3 to 11 years were recruited from Beijing Children's Hospital from 1 January 2017 to 30 June 2018.All children underwent polysomnography,and their blood pressure was monitored and calculated by the pulse transit time.The children were divided into those with primary snoring(PS),mild OSAS,and moderate to severe OSAS according to their obstructive apnea-hypopnea index(OAHI).Results:In total,140 children were included.Ninety-seven had PS,24 had mild OSAS,and 19 had moderate to severe OSAS.There were no differences in age,sex,or body mass index z-score among the groups.Statistieally significant differences were found in the OAHI,oxygen desaturation index 3%,respiratory arousal index,and lowest oxygen saturation among the three groups.Children with moderate to severe OSAS had higher systolic and diastolic blood pressure than those with mild OSAS andPS(P<0.001).In all children,systolic and diastolic blood pressure was higher in the rapid eye movement(REM)sleep stage than in the non-REM sleep stage(P<0.05).Interpretation:Children with moderate to severe OSAS had higher blood pressure than those with PS and mild OSAS in all sleep stages.Blood pressure in the REM sleep stage was higher than that in other sleep stages in all groups of children.

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.

Clinical evaluation of cochlear implantation in children younger than 12 months of age

Importance Cochlear implantation(CI)is an effective therapy for patients with severe to profound sensorineural hearing loss.It remains controversial whether children younger than 12 months of age should undergo CI.Objective To evaluate the safety and effectiveness of CI in children younger than 12 months of age.Methods We performed a retrospective study of clinical data of pediatric patients younger than 12 months of age who underwent CI and were followed up for 1 to 2 years.Patients’developmental levels were evaluated by the Gesell score before CI.Intraoperative and postoperative complications were recorded to evaluate the safety of CI.Auditory and speech abilities were scored by the LittlEARS®auditory questionnaire(LEAQ),categories of auditory performance(CAP),speech intelligibility rating(SIR),infant‐toddler meaningful auditory integration scale(IT‐MAIS),and meaningful use of speech scale(MUSS)at 1,2,3,6,9,and 12 months after CI.The associations between clinical characteristics before CI and postoperative scores at 1 year after CI were analyzed by the linear mixed‐effects model.Results Eighty‐nine children(47 boys and 42 girls)were included in this study(mean age at CI,9.2±1.6 months).Sixteen patients were diagnosed with cochlear malformation and 16 underwent bilateral CI.No severe complications occurred in any patients.The mean developmental quotient of the Gesell score was 78.00±10.03.The median LEAQ scores were 0,5,10,16,22,26 and 30 before and at 1,2,3,6,9,and 12 months after CI,respectively.These findings implied that the LEAQ score greatly improved in the first year after CI.The overall CAP,SIR,IT‐MAIS,and MUSS scores also increased with increasing duration after CI.No significant associations were detected between clinical characteristics(age,sex,implant number,pre‐CI Gesell score,and inner ear malformation)and LEAQ outcomes at 12 months after CI.Interpretation With increasing duration after CI,auditory and speech behavior dramatically improve in young children.Our findings indicate that CI is feasible for children younger than 12 months of age.

Identification of potential pathogenic mutations in Chinese children with first branchial cleft anomalies detected by whole-exome sequencing

Importance:First branchial cleft anomalies(FBCAs)are rare congenital malformations,accounting for<8%of all branchial cleft anomalies.However,little is currently known about the cause of FBCAs at the molecular level.Objective:To identify genomic alterations related to the genetic etiology of FBCAs in Chinese children.Methods:We performed whole-exome sequencing of samples from 10 pediatric patients with FBCAs.Data analysis was carried out using the Burrow-Wheeler Alignment software package,and the dbSNP database for comparisons.Rare variants were further validated by Sanger sequencing.Insertion/deletions(indels)were examined using the Genome Analysis Toolkit.Results:We identified 14 non-synonymous mutations in seven potential FBCA-susceptibility genes(TRAPPC12,NRP2,NPNT,SH3RF2,RHPN1,TENM4,and ARMCX4).We also detected 133 shared small indels in 125 genes.Gene Ontology analysis indicated that most of the identified genes played critical roles in development and differentiation pathways involved in regulating organ development.Interpretation:We characterized the mutational landscape in pathways involved in development and differentiation in Chinese children with FBCA.The results identified potential pathogenic genes and mutations related to FBCA,and provide molecular-level support for the branchial theory of FBCA pathogenesis.

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 genome analysis strategies in the clinical testing for pediatric diseases

Next-generation sequencing (NGS) is being used in clinical testing.Government authorities in both China and the United States are overseeing the clinical application of NGS instruments and reagents.In addition,the US Association for Molecular Pathology and the College of American Pathologists have jointly released a guidance to standardize the analysis and interpretation of NGS data involved in clinical testing.At present,the analysis strategies and pipelines for NGS data related to the clinical detection of pediatric disease are similar to those used for adult diseases.However,for rare pediatric diseases without linkage to known genetic variants,it is currently difficult to detect the relevant pathogenic genes using NGS technology.Additionally,it is challenging to identify novel pathogenic genes of familial pediatric tumors.Therefore,characterization of the pathogenic genes associated with above diseases is important for the diagnosis and treatment of rare diseases in children.This article introduces the general pipelines for NGS data analyses of diseases and elucidates data analysis strategies for the pathogenic genes of rare pediatric diseases and familial pediatric tumors.

Genotype-phenotype correlations,surgical selections,and postoperative complications of 5α-reductase 2 deficiency in 69 children with hypospadias

5α-reductase 2 deficiency prevents testosterone from being converted to dihydrotestosterone,which causes abnormal urogenital sinus development.The aim of this study was to analyze the relationship between genotype–phenotype,surgical selections,and postoperative complications of 5α-reductase 2-deficient patients with hypospadias.We retrospectively evaluated the medical records of patients who were diagnosed with 5α-reductase 2 deficiency after genetic testing in the Department of Endocrinology and underwent initial hypospadias surgery in the Department of Urology in Beijing Children’s Hospital,Capital Medical University(Beijing,China),from April 2007 to December 2021.A total of 69 patients were included in this study;the mean age at surgery was 34.1 months,and the average follow-up time was 54.1 months.Sixty children were treated with preoperative hormone stimulation(PHS)to promote penile growth.The average penis length and glans width were increased by 1.46 cm and 0.62 cm,respectively.The most frequent mutations were p.R227Q(39.1%,54/138),p.Q6^(*)(15.2%,21/138),p.G203S(12.3%,17/138),and p.R246Q(11.6%,16/138).In 64 patients who were followed up,43 had a one-stage operation and 21 had a staged operation,and there were significant differences in external masculinization score(EMS)(P=0.008)and the average number of operation required to cure(P<0.001)between one-stage and staged operations.PHS had a positive effect(P<0.001)on penile development.The p.R227Q mutation was associated with higher EMS and less severe hypospadias.One-stage surgery can be selected if conditions permit.The growth and development of children are acceptable in the long term,but penis growth remains unsatisfactory.Longterm complications of hypospadias should be considered during puberty.

International patterns and trends of childhood and adolescent cancer, 1978-2012

Background:This study aimed to provide a detailed analysis of the temporal trends of cancer incidence rates for individuals aged 0-19 years in selected regions globally from 1978 to 2012.Methods:Data were obtained from Volumes V-XI of Cancer Incidence in Five Continents(CI5),published by the International Agency for Research on Cancer.A total of 53 registries in 23 regions from the Americas,Asia,Europe,and Oceania that contained information on cancer incidence throughout 1978-2012(35 years)were included in this study.Joinpoint regression was used for the analysis of trends.Results:Most regions showed increasing trends in overall childhood cancer among children(aged 0-14 years)and adolescents(aged 15-19 years).Nearly all regions showed rising trends in childhood and adolescent leukemia incidence rates,whereas the incidence of lymphoma among children generally decreased.Only France,Australia,and New Zealand showed decreasing trends for malignant central nervous system(CNS)tumors among adoles-cents.Kidney cancer and bone cancer incidence rates remained stable for most regions.The incidence of thyroid cancer among adolescents increased in most regions and that of testicular cancer decreased in approximately one-half of the regions studied.Conclusion:The international temporal trends of cancer incidents among children and adolescents are varied by region,cancer type,age group,and gender,and have changed over time.

新辅助化疗与肿瘤减灭术治疗卵巢癌疗效和安全性的系统评价

目的采用系统评价和Meta分析探讨新辅助化疗(neoadjuvant chemotherapy,NACT)与肿瘤减灭术(primary debulking surgery,PDS)治疗卵巢癌的疗效和安全性。方法计算机检索6个中英文数据库,收集建库至2020年3月符合检索条件的文章,采用Revman 5.3对数据进行Meta分析。结果共纳入13项研究,包含研究对象3879例。Meta分析结果显示,NACT组与PDS组患者总生存期[MD=-1.55,95%CI(-3.17,0.07),P=0.06]和无症状生存期[MD=1.74,95%CI(1.00,2.47),P=0.06]相当;NACT组患者残留病灶≤1 cm比例大于PDS组患者[OR=2.19,95%CI(1.48,3.25),P<0.001];在安全性方面,NACT组术后死亡率[RR=0.14,95%CI(0.03,0.55),P=0.005]和并发症发生率[RR=0.48,95%CI(0.34,0.67),P<0.001]均降低。结论NACT减瘤效果和安全性优于PDS,但两种方案总生存期和无症状生存期相当。

光电化学水分解中铁酸盐光阴极的制备与改性

由n型半导体光阳极和p型半导体光阴极组成的无偏压光电化学电池通过太阳能可以将水直接转化为高能量密度的氢气,为解决太阳能利用过程中存在的间歇性和储存问题提供了一种潜在的经济有效的解决途径。金属氧化物具有低成本和易制备等优势,相比于发展较成熟的n型光阳极金属氧化物材料,传统的p型光阴极金属氧化物材料由于金属离子易受到光电腐蚀的影响,光电极寿命的提升是个很大的挑战。作为新型的金属氧化物光阴极材料,铁酸盐具有合适的带隙、较好的光稳定性、较正的起始电位以及较低的制备成本,正在成为光电化学电池实际应用中的有力竞争者。本文阐述了光电化学水分解的基本原理与提升光电极性能的一般方法,总结了近年来颇受关注的代表性铁酸盐光阴极材料CuFeO_2、CaFeO_4与LaFeO_3在制备方法、元素掺杂以及表面修饰等方面取得的重要进展,并对铁酸盐光阴极的未来发展趋势做了展望。

Pediatric reference intervals in China(PRINCE):design and rationale for a large,multicenter collaborative cross-sectional study

There is a lack of accurate pediatric reference intervals(RIs) in China, with most commonly used RIs established without consideration of the effect of age and gender. The Pediatric Reference Intervals in China(PRINCE) project aims to establish and verify pediatric RIs for 31 common laboratory measurands.The project will be a large, multicenter cross-sectional study:14,490 healthy children and adolescents aged up to 19 years will be surveyed by 10 children's hospitals and one pediatric department of a university hospital. To evaluate the feasibility and efficiency of the study methods, 602 children were surveyed in the pilot phase of the PRINCE study in April 2017: it found that some measurands were distinctly age dependent and that there were differences between values for males and females. The results of the pilot study affirmed the necessity of the PRINCE project for Chinese pediatrics. The pilot also indicated potential difficulties in the full survey, e.g., difficulties in recruiting children aged under 3 years and insufficient collection of blood samples from infants. The operation of the PRINCE project has been modified based on the findings in the pilot study toward improving the validity of the PRINCE project and promoting its openness and transparency.