Detection of the HBB: c.393T>G Mutation in Two Patients with Hypochromic Microcytic Anemia.

A novel mutation, HBB: c.393T>G on the HBB gene, was detected in two hypochromic microcytic anemia patients from Yulin, in the Guangxi Province of the People's Republic of China (PRC), by next-generation sequencing (NGS). It is a nonsense mutation causing a stop codon at amino acid 131 in exon 3 of the HBB gene. It was found in a heterozygous state in two patients who both presented severe anemia during pregnancy and moderate anemia before pregnancy; Hb A2 levels were slightly increased (more than 4.0%) in both patients. It was also detected in the father of one of the patients. This mutation was pathogenic, and caused the dominant thalassemia-like phenotypes in the two patients.

Optical coherence tomography enhanced depth imaging of chorioretinal folds in patients with orbital tumors.

AIM: To characterize spectral-domain optical coherence tomography (SD-OCT) features of chorioretinal folds in orbital mass imaged using enhanced depth imaging (EDI). METHODS: Prospective observational case-control study was conducted in 20 eyes of 20 patients, the uninvolved eye served as a control. All the patients underwent clinical fundus photography, computed tomography, EDI SD-OCT imaging before and after surgery. Two patients with cavernous hemangiomas underwent intratumoral injection of bleomycin A5; the remaining patients underwent tumor excision. Patients were followed 1 to 14mo following surgery (average follow up, 5.8mo). RESULTS: Visual acuity prior to surgery ranged from 20/20 to 20/200. Following surgery, 5 patients' visual acuity remained unchanged while the remaining 15 patients had a mean letter improvement of 10 (range 4 to 26 letters). Photoreceptor inner/outer segment defects were found in 10 of 15 patients prior to surgery. Following surgical excision, photoreceptor inner/outer segment defects fully resolved in 8 of these 10 patients. CONCLUSION: Persistence of photoreceptor inner/outer segment defects caused by compression of the globe by an orbital mass can be associated with reduced visual prognosis. Our findings suggest that photoreceptor inner/outer segment defects on EDI SD-OCT could be an indicator for immediate surgical excision of an orbital mass causing choroidal compression.

Adjuvant therapy for orbital non-rhabdomyosarcoma soft tissue sarcoma: comparison of long-term outcome between radiotherapy and chemotherapy.

AIM: To illustrate clinicopathological features of orbital non-rhabdomyosarcoma soft tissue sarcoma (NRSTS), and to compare the treatment outcome between postoperative radiotherapy (RT) and chemotherapy in a retrospective analysis nearly 20y. METHODS: A retrospective cohort study of 56 patients with orbital NRSTS were reviewed, 34 of whom received postoperative RT, and 22 received postoperative chemotherapy. The clinicopathological features, local recurrence, metastases, and survival data were recorded. Survival analysis was performed using the Kaplan-Meier method. RESULTS: During follow-up (111.8mo, ranged 8-233mo) for 56 patients, 19 patients of them developed local recurrence, and 7 patients developed distant metastases. Fifteen patients died during follow-up period. Overall survival rates considering the whole study group was 78.57% at 5y, and 72.16% at 10y after the initial diagnosis. Compared with chemotherapy, RT was associated with lower risk of local recurrence [hazard ratio for RT vs chemotherapy, 0.263, 95% confidence interval (CI), 0.095-0.728, P=0.0015]; with lower risk of distant metastasis (hazard ratio for RT vs chemotherapy, 0.073, 95%CI, 0.015-0.364, P=0.0014); and with lower risk of death from disease (hazard ratio for RT vs chemotherapy, 0.066, 95%CI, 0.022-0.200, P<0.0001). The 5-year survival rate in RT group was 97.06% compared to 50% in chemotherapy group. CONCLUSION: In patients with orbital NRSTS, postoperative RT provides better control of local recurrence, distant metastasis, and death from disease than chemotherapy. RT is the more preferrable adjuvant therapy compared to chemotherapy possibly.

Video-assisted thoracic surgery drainage is feasible and safe for acute necrotizing mediastinitis: a retrospective cohort study.

Background: Acute necrotizing mediastinitis (ANM) is a severe infection of the mediastinal loose connective tissue. Traditionally, it has been treated with thoracotomy, but video-assisted thoracic surgery (VATS) is been increasingly used in patients with this condition. This study aimed to compare the outcomes of VATS and open thoracotomy in treating ANM. Methods: The medical records of patients with ANM who underwent surgery between March 2012 and April 2021 were retrieved. A retrospective screening was conducted based on clinical characteristics, bacterial pathogens, surgical approach, and outcomes. The patients were divided into a VATS group and an open thoracotomy (Open) group. The patient characteristics and surgical outcomes of the two groups were summarized and compared. Results: A total of 64 cases were enrolled in this study, including 48 in the VATS group (75%) and 16 in the Open group (25%). The most common site of infection was the neck (n=26, 40.6%). Streptococcus constellatus and Acinetobacter baumannii (A. baumannii) were the most frequently found pathogens in secretion culture. In sputum culture, the most common pathogens were Klebsiella pneumonia and A. baumannii. Postoperative outcomes, including blood transfusion (33.3% vs. 43.8%; P=0.45), duration of postoperative drainage {14 [1-47] vs. 17 [4-54] days; P=0.15}, length of antibiotic medication {14.5 [1-54] vs. 18 [4-54] days; P=0.29}, admission to intensive care unit (ICU) (87.5% vs. 75.0%; P=0.43), length of ICU stay {5 [1-58] vs. 8.5 [1-37] days; P=0.20}, postoperative hospital stay {17 [2-61] vs. 21 [5-56] days; P=0.22}, reoperation rate (12.5% vs. 6.25%; P=0.82), and mortality rate (14.6% vs. 12.5%; P>0.99) were comparable between the two groups. Conclusions: ANM treated by both the VATS and open approach had comparable outcomes. Therefore, VATS is a viable option for patients with ANM.

Identification of representative genes of the central nervous system of the locust, Locusta migratoria manilensis by deep sequencing.

The shortage of available genomic and transcriptomic data hampers the molecular study on the migratory locust, Locusta migratoria manilensis (L.) (Orthoptera: Acrididae) central nervous system (CNS). In this study, locust CNS RNA was sequenced by deep sequencing. 41,179 unigenes were obtained with an average length of 570 bp, and 5,519 unigenes were longer than 1,000 bp. Compared with an EST database of another locust species Schistocerca gregaria Forsskåi, 9,069 unigenes were found conserved, while 32,110 unigenes were differentially expressed. A total of 15,895 unigenes were identified, including 644 nervous system relevant unigenes. Among the 25,284 unknown unigenes, 9,482 were found to be specific to the CNS by filtering out the previous ESTs acquired from locust organs without CNS's. The locust CNS showed the most matches (18%) with Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae) sequences. Comprehensive assessment reveals that the database generated in this study is broadly representative of the CNS of adult locust, providing comprehensive gene information at the transcriptional level that could facilitate research of the locust CNS, including various physiological aspects and pesticide target finding.

Arabidopsis Hormone Database: a comprehensive genetic and phenotypic information database for plant hormone research in Arabidopsis.

Plant hormones are small organic molecules that influence almost every aspect of plant growth and development. Genetic and molecular studies have revealed a large number of genes that are involved in responses to numerous plant hormones, including auxin, gibberellin, cytokinin, abscisic acid, ethylene, jasmonic acid, salicylic acid, and brassinosteroid. Here, we develop an Arabidopsis hormone database, which aims to provide a systematic and comprehensive view of genes participating in plant hormonal regulation, as well as morphological phenotypes controlled by plant hormones. Based on data from mutant studies, transgenic analysis and gene ontology (GO) annotation, we have identified a total of 1026 genes in the Arabidopsis genome that participate in plant hormone functions. Meanwhile, a phenotype ontology is developed to precisely describe myriad hormone-regulated morphological processes with standardized vocabularies. A web interface (http://ahd.cbi.pku.edu.cn) would allow users to quickly get access to information about these hormone-related genes, including sequences, functional category, mutant information, phenotypic description, microarray data and linked publications. Several applications of this database in studying plant hormonal regulation and hormone cross-talk will be presented and discussed.

Characterization of the genome expression trends in the heading-stage panicle of six rice lineages.

To study how changes in gene regulation shape phenotypic variations in rice, we performed a comparative analysis of genome expression in the heading-stage panicle from six lineages of cultivated and wild rice, including Oryza sativa subsp. indica, japonica and javanica, O. nivara , O. rufipogon and O. glaberrima. While nearly three-quarters of the genes are expressed at a constant level in all six lineages, a large portion of the genome, ranging from 1767 to 4489 genes, exhibited differential expression between Asian domesticated and wild rice with repression or down-regulation of genome expression in Asian cultivated rice as the dominant trend. Importantly, we found this repression was achieved to a large extent by the differential expression of a single member of paralogous gene families. Functional analysis of the differentially expressed genes revealed that genes related to catabolism are repressed while genes related to anabolism up-regulated. Finally, we observed that distinct evolutionary forces may have acted on gene expression and the coding sequences in the examined rice lineages.

Exome Sequencing Identifies TENM4 as a Novel Candidate Gene for Schizophrenia in the SCZD2 Locus at 11q14-21.

Schizophrenia is a complex psychiatric disorder with high genetic heterogeneity, however, the contribution of rare mutations to the disease etiology remains to be further elucidated. We herein performed exome sequencing in a Han Chinese schizophrenia family and identified a missense mutation (c.6724C>T, p.R2242C) in the teneurin transmembrane protein 4 (TENM4) gene in the SCZD2 locus, a region previously linked to schizophrenia at 11q14-21. The mutation was confirmed to co-segregate with the schizophrenia phenotype in the family. Subsequent investigation of TENM4 exons 31, 32, and 33 adjacent to the p.R2242C mutation revealed two additional missense mutations in 120 sporadic schizophrenic patients. Residues mutated in these mutations, which are predicted to be deleterious to protein function, were highly conserved among vertebrates. These rare mutations were not detected in 1000 Genomes, NHLBI Exome Sequencing Project databases, or our in-house 1136 non-schizophrenic control exomes. Analysis of RNA-Seq data showed that TENM4 is expressed in the brain with high abundance and specificity. In line with the important role of TENM4 in central nervous system development, our findings suggested that increased rare variants in TENM4 could be associated with schizophrenia, and thus TENM4 could be a novel candidate gene for schizophrenia in the SCZD2 locus.

[Application of Next Generation Sequencing to Screen the Neonatal Thalassemia Genes].

OBJECTIVE: To explore the feasibility of using next-generation sequencing technology (NGS) to screen the neonatal thalassemia genes. METHODS: Plantar blood of 206 cases of neonatal born in our hospital were randomly collected to be made into dried blood, which can be screened for thalassemia genes by next-generation sequencing, and then a further analysis would be performed on the basis on the detection results. RESULTS: In 206 cases of neonates tested, the thalassemia gene mutations in 22 cases were screened, including 11 cases of alpha-thalassemia, 11 cases of beta-thalassemia, 5 cases of new mutations. Out of 11 cases of alpha-thalassemia 7 cases were proved to be the gene deletion, accounting for 64% (7/11), and the specific genotype distribution was as follows: 4 cases of αα/-α(3.7), 2 cases of αα/-SEA, 1 case of αα/-α(4.2), the remaining 4 cases with point mutations (4/11, 36%): Hb Part-Dieu hybrid, Hb Quong Sze hybrid, Hb Westmead hybrid, HBA1: c. 95 + 9 c > T (rewly discovered gene mutation). The whole 11 cases of ß-thalassemia are proved to be with beta chain point mutations, 7 kinds of mutation genotype were detected , CD17 (A->T) is the most common point locus mutation, accounted for 27% (3/11), and 50 G>A hybrid in 2 cases, 1 cases of Hb Hamilton hybrid, IVS-II-654 (C->T) in 1 case. The remaining 4 cases are of the new gene point mutation, they are as follows respectively: HBB: c. 316-116 c>A, HBB: c.316-248G>T, HBB: c.315 + 63 T>c, HBB: c. -23 A>G. CONCLUSION: The next-generation sequencing technology can be used to screen neonatal plantar dried blood for the thalassemia genetic mutation, which not only can effectively detect thalassemia gene types, but also can look for new gene mutations. The advantages of this method include easy collecting samples, precise result and wide use for clinical diagnosis, thus possibly give an early diagnosis for thalassemia.

Transcriptome analysis of the brown planthopper Nilaparvata lugens.

BACKGROUND: The brown planthopper (BPH) Nilaparvata lugens (Stål) is one of the most serious insect pests of rice in Asia. However, little is known about the mechanisms responsible for the development, wing dimorphism and sex difference in this species. Genomic information for BPH is currently unavailable, and, therefore, transcriptome and expression profiling data for this species are needed as an important resource to better understand the biological mechanisms of BPH. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we performed de novo transcriptome assembly and gene expression analysis using short-read sequencing technology (Illumina) combined with a tag-based digital gene expression (DGE) system. The transcriptome analysis assembles the gene information for different developmental stages, sexes and wing forms of BPH. In addition, we constructed six DGE libraries: eggs, second instar nymphs, fifth instar nymphs, brachypterous female adults, macropterous female adults and macropterous male adults. Illumina sequencing revealed 85,526 unigenes, including 13,102 clusters and 72,424 singletons. Transcriptome sequences larger than 350 bp were subjected to Gene Orthology (GO) and KEGG Orthology (KO) annotations. To analyze the DGE profiling, we mainly compared the gene expression variations between eggs and second instar nymphs; second and fifth instar nymphs; fifth instar nymphs and three types of adults; brachypterous and macropterous female adults as well as macropterous female and male adults. Thousands of genes showed significantly different expression levels based on the various comparisons. And we randomly selected some genes to confirm their altered expression levels by quantitative real-time PCR (qRT-PCR). CONCLUSIONS/SIGNIFICANCE: The obtained BPH transcriptome and DGE profiling data provide comprehensive gene expression information at the transcriptional level that could facilitate our understanding of the molecular mechanisms from various physiological aspects including development, wing dimorphism and sex difference in BPH.