Preoperative serum cortisone levels are associated with cognition in preschool‑aged children with tetralogy of Fallot after corrective surgery:new evidence from human populations and mice

Background Tetralogy of Fallot(TOF)is the most common cyanotic congenital heart disease.Children with TOF would be confronted with neurological impairment across their lifetime.Our study aimed to identify the risk factors for cerebral morphology changes and cognition in postoperative preschool-aged children with TOF.Methods We used mass spectrometry(MS)technology to assess the levels of serum metabolites,Wechsler preschool and primary scale of intelligence-Fourth edition(WPPSI-Ⅳ)index scores to evaluate neurodevelopmental levels and multimodal magnetic resonance imaging(MRI)to detect cortical morphological changes.Results Multiple linear regression showed that preoperative levels of serum cortisone were positively correlated with the gyrification index of the left inferior parietal gyrus in children with TOF and negatively related to their lower visual spaces index and nonverbal index.Meanwhile,preoperative SpO_(2) was negatively correlated with levels of serum cortisone after adjusting for all covariates.Furthermore,after intervening levels of cortisone in chronic hypoxic model mice,total brain volumes were reduced at both postnatal(P)11.5 and P30 days.Conclusions Our results suggest that preoperative serum cortisone levels could be used as a biomarker of neurodevelopmental impairment in children with TOF.Our study findings emphasized that preoperative levels of cortisone could influence cerebral development and cognition abilities in children with TOF.

Water modeling on fluid flow and mixing phenomena in a BOF steelmaking converter

A 1∶8 physical water model was constructed to investigate the fluid flow and mixing phenomena in the basic oxygen furnace(BOF)converter.The particle image velocimetry was employed to measure the velocity distribution of the bath and the high-speed camera was applied to capture the cavity shape in the combined blowing BOF converter.The mixing time for varied operating conditions was measured by the stimulus-response approach.The cavity depth increased with the decrease in the lance height and the increase in the top gas flow rate while the bottom blowing gas had little influence on the cavity depth.The minimum cavity depth was obtained under the condition of a 69.8 m^(3)/h top gas flow rate,a 287.5 mm lance height and a 0.93 m^(3)/h bottom blowing gas flow rate,which was 161.2 mm.The mixing time decreased as the lance height decreased and the top blowing gas flow rate increased.The mixing time was first decreased and then increased with the increase in the bottom gas flow rate.With the condition of 69.8 m^(3)/h gas flow rate of top blowing,the 287.5 mm lance height and the 0.93 m^(3)/h gas flow rate of bottom blowing,the mixing time in the converter was 48.65 s.The empirical formula between the stirring power and the mixing time in the converter was calculated.

FoxO is required for optimal fitness of the migratory brown planthopper, Nilaparvata lugens (Hemiptera: Delphacidae)

The forkhead box O(FoxO)protein is the main transcriptional effector downstream of the insulin/insulin-like signaling pathway and regulates many developmental and physiological processes.Holometabolous insects with loss-of-function mutations in FoxO exhibit phenotypes distinct from those of hemimetabolous insects in which RNA interference was used.Despite the functional importance of FoxO,whether hemimetabolous insects share an evolutionally conserved function of FoxO with holometabolous insects remains to be clarified.We used the clustered regularly interspaced short palindromic repeats/CRISPR-associated 9(CRISPR/Cas9)genome editing-system to establish a homozygous FoxO-null mutant(NlFoxO^(4E))of the wing-dimorphic brown planthopper(BPH)Nilaparvata lugens,an economically important insect pest of rice fields.The phenotypes of NlFoxO^(4E) mutants included extended nymphal duration,shortened lifespan,reduced reproduction,and decreased stress resistance.In addition,depletion of NlFoxO promoted cell proliferation in wing buds and led to 100%long-winged morphs,in stark contrast to short-winged wild-type BPHs.These findings indicate that NlFoxO is highly functionally conserved with its counterpart in holometabolous insects,and is required for optimal fitness of N.lugens.The insights from FoxO studies may facilitate the identification of potential target genes for BPH control applications.

Efficacy and Safety of Zhuanggu Joint Capsules in Combination with Celecoxib in Knee Osteoarthritis： A Multi-center, Randomized, Double-blind, Double-dummy, and Parallel Controlled Trial

Background：Knee osteoarthritis （KOA） is a chronic joint disease that manifests as knee pain as well as different degrees of lower limb swelling,stiffness,and movement disorders.The therapeutic goal is to alleviate or eliminate pain,correct deformities,improve or restore joint functions,and improve the quality of life.This study aimed to evaluate the efficacy and safety of Zhuanggu joint capsules combined with celecoxib and the benefit of treatment with Zhuanggu alone for KOA.Methods：This multi-center,randomized,double-blind,double-dummy,parallel controlled trial,started from December 2011 to May 2014,was carried out in 6 cities,including Beijing,Shanghai,Chongqing,Changchun,Chengdu,and Nanjing.A total of 432 patients with KOA were divided into three groups （144 cases in each group）.The groups were treated,respectively,with Zhuanggu joint capsules combined with celecoxib capsule simulants,Zhuanggu joint capsules combined with celecoxib capsules,and celecoxib capsules combined with Zhuanggu joint capsule simulants for 4 weeks consecutively.The improvement of Western Ontario and McMaster Universities Osteoarthritis （WOMAC） index and the decreased rates in each dimension of WOMAC were evaluated before and after the treatment.Intergroup and intragroup comparisons of quantitative indices were performed.Statistically significant differences were evaluated with pairwise comparisons using Chi-square test （or Fisher＆#39;s exact test） and an inspection level ofα =0.0167.Results：Four weeks after treatment,the total efficacies of Zhuanggu group,combination group,and celecoxib group were 65%,80%,and 64%,respectively,with statistically significant differences among the three groups （P =0.005）.Intergroup pairwise comparisons showed that the total efficacy of the combination group was significantly higher than that of the Zhuanggu （P =0.005） and celecoxib （P =0.003）groups.The difference between the latter two groups was not statistically significant （P 〉 0.0167）.Four weeks after discontinuation,the efficacies of the three groups were 78%,95%,and 65%,respectively,with statistically significant differences （P 〈 0.0001）.Intergroup pairwise comparisons revealed that the efficacy of the combination group was significantly better than that of the Zhuanggu and the celecoxib groups （P 〈 0.0001）.The difference between the latter two groups was not statistically significant （P 〉 0.0167）.The incidences of adverse events in Zhuanggu group,combination group,and celecoxib group were 8.5%,8.5%,and 11.1%,respectively,with insignificant differences （P 〉 0.05）.Conclusions：Zhuanggu joint capsules alone or combined with celecoxib showed clinical efficacy in the treatment of KOA.The safety of Zhuanggu joint capsules alone or combined with celecoxib was acceptable.

Three-Dimensional Heterogeneity of Cerebellar Interposed Nucleus-Recipient Zones in the Thalamic Nuclei

The cerebellum is conceptualized as a processor of complex movements and is also endowed with roles in cognitive and emotional behaviors.Although the axons of deep cerebellar nuclei are known to project to primary thalamic nuclei,macroscopic investigation of the characteristics of these projections,such as the spatial distribution of recipient zones,is lacking.Here,we studied the output of the cerebellar interposed nucleus(IpN)to the ventrolateral(VL)and centrolateral(CL)thalamic nuclei using electrophysiological recording in vivo and trans-synaptic viral tracing.We found that IpN stimulation induced mono-synaptic evoked potentials(EPs)in the VL but not the CL region.Furthermore,both the EPs induced by the IpN and the innervation of IpN projections displayed substantial heterogeneity across the VL region in three-dimensional space.These findings indicate that the recipient zones of IpN inputs vary between and within thalamic nuclei and may differentially control thalamo-cortical networks.