KIF2A regulates ovarian development via modulating cell cycle progression and vitollogenin levels

The kinesin superfamily of proteins (KIFs) are microtubule motor proteins that use the hydrolysis of ATP to power directional movement along microtubules. KIFs induce microtubule depolymerization to regulate the length and dynamics of microtubules in a variety of cell processes and structures, including the mitotic and meiotic spindles and centriole and interphase microtubules. KIF plays a significant role in the transport of organelles, protein complexes and mRNAs. The brown planthopper (Nilaparvata lugens) is a major insect pest in rice paddy fields. Ovarian development is regulated by multiple factors, including endocrine factors. The role of KIFs in brown planthopper ovarian development remains unknown. We found that downregulation of KIF2A significantly compromised the development and eclosion of the brown planthopper, delayed ovarian cell cycle progression, disrupted ovarian development, reduced the expression of MCM genes required for DNA replication and significantly reduced the number of nuclei in the follicles. We also found a significant reduction in Vg mRNA and protein levels. We conclude that downregulation of KIF2A disrupts the cell cycle progression of cells. Alternatively, the ovarian phenotype could be an indirect effect of a compromised trophic cord. In summary, KIF2A regulates ovarian development via modulating cell cycle progression and/or vitollogenin transportation.     

Identification of key genes and pathways in discoid lupus skin via bioinformatics analysis

Discoid lupus erythematosus (DLE) is the most common skin manifestation of lupus; however, the molecular mechanisms underlying DLE remain unknown. Therefore, we aimed to identify key differentially expressed genes (DEGs) in discoid lupus skin and investigate their potential pathways.To identify candidate genes involved in the occurrence and development of the disease, we downloaded the microarray datasets {"type":"entrez-geo","attrs":{"text":"GSE52471","term_id":"52471"}}GSE52471 and {"type":"entrez-geo","attrs":{"text":"GSE72535","term_id":"72535"}}GSE72535 from the Gene Expression Database (GEO). DEGs between discoid lupus skin and normal controls were selected using the GEO2R tool and Venn diagram software (http://bioinformatics.psb.ugent.be/webtools/Venn/). The Database for Annotation, Visualization, and Integrated Discovery (DAVID), Enrichr, and Cytoscape ClueGo were used to analyze the Kyoto Encyclopedia of Gene and Genome pathways and gene ontology. Protein-protein interactions (PPIs) of these DEGs were further assessed using the Search Tool for the Retrieval Interacting Genes version 10.0.Seventy three DEGs were co-expressed in both datasets. DEGs were predominantly upregulated in receptor signaling pathways of the immune response. In the PPI network, 69 upregulated genes were selected. Furthermore, 4 genes (CXCL10, ISG15, IFIH1, and IRF7) were found to be significantly upregulated in the RIG-I-like receptor signaling pathway, from analysis of Enrichr and Cytoscape ClueGo.The results of this study may provide new insights into the potential molecular mechanisms of DLE. However, further experimentation is required to confirm these findings.     

Pediatric Wilson disease presenting as acute liver failure: Prognostic indices

BACKGROUNDAcute liver failure (ALF) can be a primary presentation of Wilson disease (WD). Mortality rates are high in WD with ALF (WDALF). Predictions of mortality in WDALF vary by model and are sometimes contradictory, perhaps because few patients are studied or WD diagnoses are questionable. AIMTo determine the outcomes among well-documented WDALF patients and assess mortality model performance in this cohort.METHODSWe reviewed the medical records of our pediatric WDALF patients (n = 41 over 6-years-old, single-center retrospective study) and compared seven prognostic models (King’s College Hospital Criteria, model for end-stage liver disease/pediatric end-stage liver disease scoring systems, Liver Injury Unit [LIU] using prothrombin time [PT] or international normalized ratio [INR], admission LIU using PT or INR, and Devarbhavi model) with one another.RESULTSAmong the 41 Han Chinese patients with ALF, WD was established by demonstrating ATP7B variants in 36. In 5 others, Kayser-Fleischer rings and Coombs-negative hemolytic anemia permitted diagnosis. Three died during hospitalization and three underwent liver transplantation (LT) within 1 mo of presentation and survived (7.3% each); 35 (85.4%) survived without LT when given enteral D-penicillamine and zinc-salt therapy with or without urgent plasmapheresis. Parameters significantly correlated with mortality included encephalopathy, coagulopathy, and gamma-glutamyl transpeptidase activity, bilirubin, ammonia, and serum sodium levels. Area under the receiver operating curves varied among seven prognostic models from 0.981 to 0.748 with positive predictive values from 0.214 to 0.429.CONCLUSIONWDALF children can survive and recover without LT when given D-penicillamine and Zn with or without plasmapheresis, even after enlisting for LT.     

Partial trisomy 16q and partial monosomy 7p of a fetus derivated from paternal balanced translocation: A case report

Introduction:Subchromosomal deletions and duplications could currently be detected by noninvasive preliminary screening (NIPS). However, NIPS is a screening test that requires further diagnosis. Here we report a fetus with an autosomal abnormality revealed by NIPS and conventional karyotype combined with copy number variations sequencing (CNV-seq) confirmed the fetus with an unbalanced translocation.Patient concern:This was the fourth pregnancy of a 30-year-old woman who underwent 2 spontaneous abortions and gave birth to a child with a normal phenotype. The woman and her husband were healthy and nonconsanguineous. NIPS indicated a repeat of about 19-Mb fragment at the region of 16q22.1-q22.4 at 17-week gestation.Diagnoses:The combination of traditional karyotype and CNV-seq could better locate the abnormal chromosomal region and further identify the source of fetal chromosomal abnormalities. Simultaneously, we evaluated the fetal morphology by ultrasound examination. The karyotype of the fetus was 46,XX,der(7)t(7;16)(p22;q23) and CNV-seq results showed an approximately 20.96-Mb duplication in 16q22.1-q24.3 (69200001-90160000) and an approximately 3.86-Mb deletion in 7p22.3-p22.2 (40001-3900000). Prenatal ultrasound revealed the fetal micrognathia. The paternal karyotype was 46,XY, t (7;16) (p22;q23), while the maternal was normal. The fetus inherited an abnormal chromosome 7 from its father.Interventions:No treatment for the fetus.Outcomes:Pregnancy was terminated.Conclusions:To our knowledge, the occurrence of de novo partial trisomy 16q (16q22.1-qter) and partial monosomy 7p (7p22.2-pter) has not previously been reported up to now. Here, we present the perinatal findings of such a case and a review of the literatures. CNV-seq combined with karyotype is a useful tool for chromosomal abnormalities indicated by NIPS.     

随访数据信息化管理系统对超声医师诊断效能的影响

目的探讨随访数据信息化管理系统的构建，并研究该系统对超声医师诊断效能的影响。 方法回顾性分析2016年7月至2018年12月北京大学深圳医院的8951个病例，均经病理证实。采用分级诊断构建随访数据信息化管理系统。所有病例采用诊断等级（1~3级，每个等级细分为诊断符合与不符合）并进行诊断加权分评估。计算随访效率（随访每100个有效病例所需要的人员和时间）。超声医师诊断效能通过诊断等级、诊断符合率及诊断加权分评价。采用χ²检验比较随访数据信息化管理系统构建前后超声医师诊断等级、诊断符合率的差异，采用t检验比较诊断加权分的差异。 结果随访工作占用成本由随访系统构建前的5.2人时/100例降低至构建后的3.1人时/100例。随访数据信息化管理系统构建前、后诊断等级比较（1级/2级/3级∶21.0%/21.0%/58.0% vs 17.3%/23.9%/58.8%），差异有统计学意义（χ²=23.708，P＜0.001），构建后的诊断等级优于构建前，对病变良恶性作出判断病例（2级+3级）的构成比增加（82.7% vs 79.0%）。系统构建后1级、3级诊断符合率与系统构建前比较有所提高（83.8% vs 66.6%；87.8% vs 85.7%），差异均具有统计学意义（χ²=361.453、5.573，P＜0.001、=0.020）；2级诊断符合率比较，差异无统计学意义（P＞0.05）。超声医师诊断加权分均值从3.93分提高至4.51分，差异具有统计学意义（t=-14.816，P＜0.001）。 结论随访数据信息化管理系统的构建能提高随访效率，并定量评价超声医师的诊断效能，通过系统反馈和校正的方式可提高超声医师的诊断效能。     

Ultra-High Performance Liquid Chromatography/Ion Mobility-Quadrupole Time-of-Flight Mass Spectrometry and Database-Driven Automatic Peak Annotation for the Rapid Profiling and Characterization of the Multicomponents from Stephaniae Tetrandrae Radix (Fang-Ji)

Quality control of traditional Chinese medicine (TCM) begins with elucidation of its chemical basis. The root of Stephania tetrandra, Stephaniae Tetrandrae radix (STR; Fang-Ji), has long been utilized as an antirheumatic, analgesic, and diuretic TCM. Powerful analytical strategies that would enable a multicomponent characterization of STR are still lacking. In the present study, we established a rapid, reliable, and enhanced profiling approach, using ultra?high performance liquid chromatography coupled with ion mobility/quadrupole time?of?flight mass spectrometry (MS) and automatic peak annotation facilitated by computational matching of an in?house library. This approach was used to characterize the multicomponents of STR. Good chromatographic separation was achieved within 17 min on a reversed-phase BEH C18 column eluted with acetonitrile/0.1% ammonium hydroxide in water, whereas data?independent high?definition MSE in the positive mode was applied to acquire the MS2 data using a Vion? IM?QTOF instrument, which, in theory, could cover all the profiled precursor ions. To overcome the interference of three predominant peaks, a knockout strategy was utilized by automated valve switching. An in?house library of 163 compounds was established and incorporated into the UNIFI? platform. By applying this method, we could identify or tentatively characterize 76 alkaloidsfrom the methanolic extract of STR, including 14 aporphine?type, four morphine?type, 48 bisbenzylisoquinoline?type, seven tetrahydroprotoberberine?type, one protopine?type, one benzylisoquinoline?type, and one other. For each component, four?dimensional information, such as retention time, collision cross-section, high-accuracy MS1, and high-accuracy MS2 data, was utilized to achieve the systematic multicomponent characterization of STR.     

Serum alpha-fetoprotein and clinical outcomes in patients with advanced hepatocellular carcinoma treated with ramucirumab

Background Post hoc analyses assessed the prognostic and predictive value of baseline alpha-fetoprotein (AFP), as well as clinical outcomes by AFP response or progression, during treatment in two placebo-controlled trials (REACH, REACH-2).Methods Serum AFP was measured at baseline and every three cycles. The prognostic and predictive value of baseline AFP was assessed by Cox regression models and Subpopulation Treatment Effect Pattern Plot method. Associations between AFP (≥ 20% increase) and radiographic progression and efficacy were assessed.Results Baseline AFP was confirmed as a continuous (REACH, REACH-2; p < 0.0001) and dichotomous (≥400 vs. <400 ng/ml; REACH, p < 0.01) prognostic factor, and was predictive for ramucirumab survival benefit in REACH (p = 0.0042 continuous; p < 0.0001 dichotomous). Time to AFP (hazard ratio [HR] 0.513; p < 0.0001) and radiographic (HR 0.549; p < 0.0001) progression favoured ramucirumab. Association between AFP and radiographic progression was shown for up to 6 (odds ratio [OR] 5.1; p < 0.0001) and 6–12 weeks (OR 1.8; p = 0.0065). AFP response was higher with ramucirumab vs. placebo (p < 0.0001). Survival was longer in patients with an AFP response than patients without (13.6 vs. 5.6 months, HR 0.451; 95% confidence interval, 0.354–0.574; p < 0.0001).Conclusions AFP is an important prognostic factor and a predictive biomarker for ramucirumab survival benefit. AFP ≥ 400 ng/ml is an appropriate selection criterion for ramucirumab.Clinical Trial Registration ClinicalTrials.gov, REACH ({"type":"clinical-trial","attrs":{"text":"NCT01140347","term_id":"NCT01140347"}}NCT01140347) and REACH-2 ({"type":"clinical-trial","attrs":{"text":"NCT02435433","term_id":"NCT02435433"}}NCT02435433).Subject terms: Oncology, Biomarkers     

Deletion of Krüppel-like factor-4 promotes axonal regeneration in mammals

Axonal regeneration plays an important role in functional recovery after nervous system damage. However, after axonal injury in mammals, regeneration is often poor. The deletion of Krüppel-like factor-4 (Klf4) has been shown to promote axonal regeneration in retinal ganglion cells. However, the effects of Klf4 deletion on the corticospinal tract and peripheral nervous system are unknown. In this study, using a mouse model of sciatic nerve injury, we show that the expression of Klf4 in dorsal root ganglion sensory neurons was significantly reduced after peripheral axotomy, suggesting that the regeneration of the sciatic nerve is associated with Klf4. In vitro, dorsal root ganglion sensory neurons with Klf4 knockout exhibited significantly enhanced axonal regeneration. Furthermore, the regeneration of the sciatic nerve was enhanced in vivo following Klf4 knockout. Finally, AAV-Cre virus was used to knockout the Klf4 gene in the cortex. The deletion of Klf4 enhanced regeneration of the corticospinal tract in mice with spinal cord injury. Together, our findings suggest that regulating KLF4 activity in neurons is a potential strategy for promoting axonal regeneration and functional recovery after nervous system injury. This study was approved by the Animal Ethics Committee at Soochow University, China (approval No. SUDA20200316A01).

Chinese Library Classification No.R456; R741; Q344+.14