CDKN1C gene mutation causing familial Silver–Russell syndrome:A case report and review of literature

BACKGROUND Cyclin-dependent kinase inhibitor 1C(CDKN1C)is a cell proliferation inhibitor that regulates the cell cycle and cell growth through G1 cell cycle arrest.CDKN1C mutations can lead to IMAGe syndrome(CDKN1C allele gain-of-function mutations lead to intrauterine growth restriction,metaphyseal dysplasia,adrenal hypoplasia congenital,and genitourinary malformations).We present a Silver-Russell syndrome(SRS)pedigree that was due to a missense mutation affecting the same amino acid position,279,in the CDKN1C gene,resulting in the amino acid substitution p.Arg279His(c.836G>A).The affected family members had an SRS phenotype but did not have limb asymmetry or adrenal insufficiency.The amino acid changes in this specific region were located in a narrow functional region that contained mutations previously associated with IMAGe syndrome.In familial SRS patients,the PCNA region of CDKN1C should be analysed.Adrenal insufficiency should be excluded in all patients with functional CDKN1C variants.CASE SUMMARY We describe the case of an 8-year-old girl who initially presented with short stature.Her height was 91.6 cm,and her weight was 10.2 kg.Physical examination revealed that she had a relatively large head,an inverted triangular face,a protruding forehead,a low ear position,sunken eye sockets,and irregular cracked teeth but no limb asymmetry.Family history:The girl’s mother,greatgrandmother,and grandmother’s brother also had a prominent forehead,triangular face,and severely proportional dwarfism but no limb asymmetry or adrenal insufficiency.Exome sequencing of the girl revealed a new heterozygous CDKN1C(NM_000076.2)c.836G>A mutation,resulting in a variant with a predicted evolutionarily highly conserved arginine substituted by histidine(p.Arg279His).The same causative mutation was found in both the proband’s mother,great-grandmother,and grandmother’s brother,who had similar phenotypes.Thus far,we found an SRS pedigree,which was due to a missense mutation affecting the same amino acid position,279,in the CDKN1C gene,resulting in the amino acid substitution p.Arg279His(c.836G>A).Although the SRS-related CDKN1C mutation is in the IMAGe-related mutation hotspot region[the proliferating cell nuclear antigen(PCNA)domain],no adrenal insufficiency was reported in this SRS pedigree.The reason may be that the location of the genomic mutation and the type of missense mutation determines the phenotype.The proband was treated with recombinant human growth hormone(rhGH).After 1 year of rhGH treatment,the height standard deviation score of the proband increased by 0.93 standard deviation score,and her growth rate was 8.1 cm/year.No adverse reactions,such as abnormal blood glucose,were found.CONCLUSION Functional mutations in CDKN1C can lead to familial SRS without limb asymmetry,and some patients may have glucose abnormalities.In familial SRS patients,the PCNA region of CDKN1C should be analysed.Adrenal insufficiency should be excluded in all patients with functional CDKN1C variants.

气管插管与非气管插管静脉复合麻醉在食管胃静脉曲张内镜治疗中的对比分析

背景食管胃静脉曲张(esophageal-gastro varices, EGV)是肝硬化常见并发症之一,如其破裂出血则具有发病急、病情重的特点,是肝硬化患者主要死因之一.无痛内镜下治疗是EGV破裂出血的重要措施,目前临床上有气管插管与非气管插管麻醉两种方式,本文拟讨论对两种麻醉方式的安全性及经济性,可在一定程度上指导临床治疗.目的探讨比较EGV内镜治疗中气管插管与非气管插管静脉复合麻醉的安全性及经济性.方法选择2017-09/2018-08石河子大学医学院第一附属医院行EGV内镜治疗的58例非活动性出血期患者,随机分为静脉复合麻醉组(非插管组)28例和气管插管静脉复合麻醉组(插管组)30例,对两组患者基本情况、安全性和经济性进行对比分析.计量资料用t检验或秩和检验,计数资料用卡方检验.结果非插管组患者术中血氧饱和度较插管组下降(P <0.05),血压、心率等生命征两组无明显差异(P>0.05);术中非插管组患者出现恶心、呛咳、呃逆、打鼾等反应,发生率均高于插管组,但程度较轻,对操作影响不大;非插管组麻醉诱导时间、苏醒时间、手术总时间均短于插管组(P<0.01),内镜治疗时间无明显差异(P>0.05);麻醉费用对比插管组高于非插管组(P<0.01),内镜治疗费用、总住院费用及住院天数两组无明显差异(P>0.05).结论对于非活动性出血期EGV内镜治疗患者,气管插管与非气管插管静脉复合麻醉均可提供良好的麻醉环境,内镜治疗效果无明显差异,且非气管插管静脉复合麻醉诱导时间短,苏醒快,麻醉费用低,是一种安全、经济的麻醉方式.

A survey of high risk factors affecting retinopathy in full-term infants in China

AIM: To investigate the possible relationship between the influencing factors occurring before and during birth in full-term infants and the outcome of retinopathy. METHODS: Totally 816 full-term infants admitted in the neonate intensive unit of Boai Hospital of Zhongshan between 1 May, 2008 and 30 June, 2011 were included in the study. Fundus examination was performed and evaluated individually on them at the age of 48 hours after delivery, 2 weeks and 1 month. Some possible risk factors happening prenatally or during delivery such as pregnant related hypertension, placenta previa, placental abruption etc, as well as some neonatal risk factors such as neonatal asphyxia, hypoxic-ischemic encephalopathy (HIE), low birth weight etc, were recorded and evacuated. Then the effect of the risk factors of full-term infants on retinopathy was studied. RESULTS: The incidence of retinal hemorrhage of full-term infants with prenatal pregnant related hypertension (PRH) of the mother (43.6%) was significantly higher than that of full-term infants without (8.0%). (P<0.001). The incidence of retinal hemorrhage of full-term infants with neonatal asphyxia and /or hypoxic-ischemic encephalopathy (HIE)(29.3%) was significantly higher than that of those without (15.7%), but correlation was not found between the severity of retina hemorrhage and the degree of hypoxic disease. A pale color of optic disc was associated with a low birth weight of full-term infant. Full-term infants with birth weigh-less than 2500g had a significant higher incidence of retinopathy than those with birth weight equal or more than 2500g( P<0.001). CONCLUSION: The main influencing factors which lead to retinopathy of high risk full-term infants are prenatal factors such as PRH, and some neonatal risk factors such as asphyxia, hypoxic-ischemic encephalopathy, and low birth weight.

Effects of muddy water irrigation with different sediment gradations on nitrogen transformation in agricultural soil of Yellow River Basin

Muddy water irrigation has been widely practiced in the Yellow River Basin for agricultural production and is an important method of economical and intensive utilization of water resources.In this study,the effects of sediment gradation,sand content,and soil moisture content on nitrogen(N)transformation were studied through a series of experimental tests.The results indicated that muddy water irrigation significantly affected agricultural soil physical and biological properties as well as N transformation.Soil bulk density,total porosity,pH,and microbial enzyme activities significantly correlated with N transformation as affected by the interaction between sediment and soil moisture.Sediment addition generally increased the soil bulk density and reduced the soil porosity and pH significantly,and the optimum moisture for promotion of the N transformation rate was 80%of the water-filled pore space.Therefore,muddy water irrigation has a potentially long-term influence on agricultural N cycles in semi-arid regions of northwestern China.This could provide a theoretical basis for scientific and rational use of muddy water for irrigation.

A 7-year-old boy with recurrent cyanosis and tachypnea:A case report

BACKGROUND Brain tumors are the most common solid tumors in children and comprise 25%of all malignancies in children.Common presentations include headache,nausea and vomiting,gait abnormality,papilledema,and epileptic seizure;however,some symptoms can be very insidious,with atypical and misleading manifestations.CASE SUMMARY Here,we report a 7-year-old boy who presented with recurrent cyanosis and tachypnea after exercise for 2 years.His body mass index was 26.43 kg/m2.Hepatosplenomegaly,blood gas analysis,biochemical parameters,chest computed tomography scan,and echocardiograph suggested type II respiratory failure,pulmonary heart disease,and mild liver injury.Non-invasive breathing support,antibiotics,and anti-heart failure therapy were given.The patient’s pulse oxygen saturation increased to over 95%when he was awake but dropped to 50%-60%,accompanied by cyanosis,during sleep while receiving high-flow nasal cannula oxygen.Sleep-related breathing disorder was suspected.In the intensive care unit,however,polysomnography was unavailable.Brain magnetic resonance imaging revealed a space-occupying(cerebellum and brainstem)lesion,which was later confirmed to be pleomorphic xanthoastrocytoma by surgery and histopathology by tissue biopsy.CONCLUSION When treating patients with cyanosis and tachypnea,a broad differential diagnosis should be considered,including brain tumor.

Pulmonary lymphomatoid granulomatosis in a 4-year-old girl:A case report

BACKGROUND Pulmonary lymphomatoid granulomatosis(PLG)is a lymphoproliferative disease associated with Epstein-Barr viral infection occurring mainly in adults and rarely in children.It is characterized by multiple pulmonary nodules.Its diagnosis depends on lung biopsy findings.Most patients are immunodeficient,and it commonly presents in children undergoing chemotherapy for leukemia.We report the case of a child with PLG caused by a mutation in the macrophageexpressed gene 1(MPEG1),suggesting possible PLG occurrence in children undergoing treatment for pulmonary nodular lesions.CASE SUMMARY This study reports a case of PLG without apparent immunodeficiency,suggesting the possibility of this disease occurrence during the treatment of pulmonary nodular lesions in children.Initially,the cause was assumed to be an atypical pathogen.Following conventional anti-infective treatment,chest computed tomography findings revealed that there were still multiple nodules in the lungs.Additionally,the patient was found to be infected with the Epstein-Barr virus.Histopathological examination of the resected lung revealed lymphoproliferative lesions with necrosis.Small lymphocytes,plasma cells,and histiocytes were observed in the background,although Reed-Sternberg cells were absent.Immunohistochemical staining[CD20(+),CD30(+),and CD3(+)]and EBV-encoded small RNA1/2 in situ hybridization of small lymphocytes revealed approximately 200 cells/high-power field.Whole exon sequencing of the patient revealed a mutation in the MPEG1.The patient was eventually diagnosed with PLG and transferred to the Department of Pediatric Oncology for bone marrow transplantation.CONCLUSION As PLG is rare and fatal,it should be suspected in clinical settings when treatment of initial diagnosis is ineffective.

Impacts of air pollution and meteorological conditions on dry eye disease among residents in a northeastern Chinese metropolis:a six-year crossover study in a cold region

The purpose of this study is to explore the associations among dry eye disease(DED),air pollution,and meteorological conditions in the cold region of a northeastern Chinese metropolis(i.e.,Changchun).Data on ambient air pollutants and meteorological parameters as well as diagnosed DED outpatients during 2015–2021 were collected.The associations between DED and environmental factors were analysed at multiple time scales using various statistical methods(i.e.,correlation,regression and machine learning).Among the 10,809 DED patients(21,617 eyes)studied,64.60%were female and 35.40%were male.A higher frequency of DED was observed in March and April,followed by January,August and October.Individual and multiple factor models showed the positive importance of particles with aerodynamic diameters<10μm(PM10),carbon monoxide(CO),and ozone(O_(3))among normal air pollutants and air pressure(AP),air temperature(AT)and wind speed(WS)among normal meteorological parameters.Air pollutants(PM10,nitrogen dioxide:NO_(2))and meteorological parameters(AT,AP)have combined impacts on DED occurrence.For the first time,we further explored the associations of detailed components of atmospheric particles and DED,suggesting potential emission sources,including spring dust from bare soil and roads and precursor pollutants of summer O_(3)formation from vehicles and industry in Northeast China.Our results revealed the quantitative associations among air pollutants,meteorological conditions and DED outpatients in cold regions,highlighting the importance of coordinated policies in air pollution control and climate change mitigation.

Fluorescence detection of hydroxyl radical generated from oxygen reduction on Fe/N/C catalyst

Pyrolyzed Fe/N/C catalyst has been considered as the most promising candidate to replace Pt for oxygen reduction reaction(ORR) in fuel cells.However,poor stability of Fe/N/C catalyst,mainly attributed to the oxidation corrosion by aggressive ·OH radical,severely hampers its applications.However,the exact mechanism for generation of ·OH is unclear yet.Herein,we developed a fluorescent method to effectively detect ·OH generated from ORR on Fe/N/C catalyst by using coumarin as a fluorescent probe.A great difference in potential dependence between ·OH and H2O2 generated from the ORR was observed,which suggests that ·OH is not generated from the decomposition of H2O2 as traditional viewpoint.

Sleep fragmentation as an important clinical characteristic of sleep disorders in Parkinson's disease: a preliminary study

Background:Sleep disorders are one of the earliest non-motor symptoms of Parkinson's disease (PD).Sleep disorders could,therefore,have value for recognition and diagnosis in PD.However,no unified classification and diagnostic criteria exist to evaluate sleep disorders by polysomnography (PSG).Utilizing PSG to monitor sleep processes of patients with PD and analyze sleep disorder characteristics and their relationship with demographic parameters could aid in bridging this gap.This preliminary study aimed to evaluate the clinical characteristic of sleep disorders in PD using PSG.Methods:PSG was used to evaluate sleep disorders in 27 patients with PD and 20 healthy volunteers between August 2015 and July 2018 in Fujian Medical University Union Hospital.Total sleep time (TST),sleep efficiency (SE),total wake time,and other parameters were compared between the two groups.Finally,the correlation between sleep disorders and age,disease duration,Unified Parkinson's Disease Rating Scale-Ⅲ scores,Hoehn-Yahr stage,and levodopa dose were analyzed.The main statistical methods included Chi-square test,two independent samples t test,Fisher exact test,and Pearson correlation.Results:Sleep fragmentation in the PD group was significantly increased (74.1%) while difficulty falling asleep and early awakening were not,as compared to healthy controls.No significant differences were found in time in bed,sleep latency (SL),non-rapid eye movement (NREM) stage 1 (N1),N1%,N2,N2%,N3%,and NREM% between PD and control groups;but TST (327.96± 105.26 min vs.414.67 ± 78.31 min,P =0.003),SE (63.26%± 14.83% vs.76.8%± 11.57%,P =0.001),R N3 (20.00 [39.00] min vs.61.50 [48.87] min,P=0.001),NREM (262.59 ± 91.20 min vs.337.17± 63.47 min,P=0.003),rapid-eyemovement (REM)(32.50 [33.00] min vs.85.25 [32.12] min,P < 0.001),REM%(9.56 ± 6.01 vs.15.50 ± 4.81,P =0.001),REM sleep latency (157.89 ± 99.04 min vs.103.47 ± 71.70 min,P =0.034) were significantly reduced in PD group.Conclusion:This preliminary study supported that sleep fragmentation was an important clinical characteristic of sleep disorders in PD.Whether sleep fragmentation is a potential quantifiable marker in PD needs to be further investigated in the future study.

Effect of controlled rolling/controlled cooling parameters on microstructure and mechanical properties of the novel pipeline steel

The study of controlled rolling/controlled cooling process parameters which affect the microstructure and mechanical properties of a novel pipeline steel has been optimized by the orthogonal experiment with four factors and three levels in this paper. However, the parameters of thermo-mechanical control process （TMCP） optimized by the Gleeble-3500 hot simulator could not satisfy performance requirements of the X100 pipeline steel. In order to improve the performance of this steel, the influence of finish cooling temperature （FCT） on the microstructure and property is studied in detail. It is found that, as this steel is thermo-mechanically treated by this set of parameters （the start heating temperature, finish rolling temperature （FRT）, FCT and cooling rate of 1,180 ℃, 810 ℃, 350 ℃ and 35 ℃/s, respectively）, the micro- structures are mainly composed of granular bainite （GB） and acicular ferrite （AF）. The effective grain sizes are below 20 μm; the steel reaches the optimal balance between the strength and the toughness; the yield strength is 695 MPa; the tensile strength is 768 MPa; the elongation is 16.6 %; the impact energy is 262 J at room temperature. All indexes could meet the requirements of X100 pipeline steel.

A review on recent developments of vanadium-based cathode for rechargeable zinc-ion batteries

Benefiting from their high safety,low cost,and excellent performance,aqueous zinc-ion batteries are regarded as a promising candidate for next-generation commercial energy storage devices.High-performance cathodes are urgently needed to accelerate practical application of zinc-ion batteries(ZIBs).Among various cathodes reported previously,vanadium-based materials attract a great deal of attention since they hold high capacity and good cycling stability.Though fruitful achievements have been made,there are amounts of crystal structures and energy storage mechanisms are still unclear,which will significantly affect performance of full batteries.This review presents a comprehensive overview of structure characteristics,relevant electrochemical behavior,and proposed energy storage mechanisms of reported vanadium-based materials which provide effective Zn-storage performance.Meanwhile,recent developments of vanadium-based materials for ZIBs are systematically summarized.Last but not least,the future perspectives are also discussed.We hope that this review can provide suggestions to design high-performance electrode materials and promote the development of ZIBs.

Development and application of a new random walk model to simulate the transport of degradable pollutants

To simulate the pollutant transport with seif-purification in inland waters,the widely used random walk model(RWM)is modified to include a source term for the degradation and to consider the impact of land boundaries.The source term for the degradation is derived from the assumption of the first-order reaction kinetics.Parameters for the new model are determined by a comparison to the analytical results.The proposed model is then applied to simulate and analyze the transport of a test pollutant and its spatial distribution in a large reservoir in northeast China.Reasonable results are obtained,and the effects of the runoff,the flow structure,and the wind on the pollutant transport are analyzed.The results may help the risk assessment and the management of the water pollution in inland waters.

A conceived model of“physician scientist”cultivation:exploring the double degrees of MD-PhD program

To the Editor:With the rapid economic growth and improvement of people's living standards in China,ever-greater demands for high-level health-care services hre expected.These expectations are bringing new challenges to the development of clinical doctors.However,the traditional path for doctor training is inadequate to meet these challenges,as both clinical and scientific practices are important for doctors but difficult to integrate into medical education.Thus,the current medical training system is challenged to combine scientific research training with conventional clinical training.To provide possible sol-utions,Health Science Center(HSC)of Xian Jiaotong University(XJTU)has been exploring a new mode of developing physician scientists:The Double Doctoral Program(DDP)。