Diagnosis of Neurological Infections in Pediatric Patients from Cell-Free DNA Specimens by Using Metagenomic Next-Generation Sequencing.

Central nervous system (CNS) infections can cause significant morbidity and mortality, especially in children. Rapid and accurate pathogenic detection in suspected CNS infections is essential for disease control at the early stage of infection. To evaluate the performance of metagenomic next-generation sequencing (mNGS) of cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) in pediatric patients, we retrospectively analyzed the efficiency of cfDNA mNGS in children with CNS infections (n = 257) or noninfectious neurological disorders (n = 81). The CSF samples of 124 random subjects were used to evaluate the accuracy between mNGS of cfDNA and whole-cell DNA (wcDNA). In total, cfDNA mNGS detected a wide range of microbes with a detection rate of 71.0%, and the sensitivity and total coincidence rate with clinical diagnosis reached 68.9% and 67.5%, respectively. Compared with wcDNA mNGS, cfDNA mNGS had a higher efficacy in detecting viruses (66 versus 13) and Mycobacterium (7 versus 1), with significantly higher reads per million. The dominant causative pathogens were bacteria and viruses in CNS infections, but these presented with different pathogen spectra in different age categories. The best timing for the mNGS test ranged from 1 to 6 days after the start of anti-infection therapy, and the earlier mNGS started, the better was identification of bacterial CNS infections. This study emphasized that cfDNA mNGS had overall superiority to conventional methods on causative pathogen detection in pediatric CNS infections, and it was even better than wcDNA mNGS. Furthermore, research needs to be better validated in large-scale clinical trials to improve the clinical applications of cfDNA mNGS. IMPORTANCE Our study emphasized that cfDNA mNGS had overall superiority to conventional methods on causative pathogen detection in CNS-infected children, and it was even better than wcDNA mNGS. cfDNA mNGS detected a wide range of pathogens with a high total coincidence rate (67.5%) against clinical diagnosis. The best timing for cfDNA mNGS detection ranged from 1 to 6 days, rather than 0 days, after the start of empirical anti-infection therapy. The earlier mNGS started, the better the identifications of bacterial CNS infections. To the best of our knowledge, this research is the first report evaluating the clinical utility of mNGS with different methods (cfDNA versus wcDNA) of extracting DNA from CSF specimens in diagnosing pediatric CNS infections. Meanwhile, this is the largest cohort study that has evaluated the performance of mNGS using cfDNA from CSF specimens in pediatric patients with CNS infections.

Psychological outcomes and associated factors amongst healthcare workers during a single wave, deeper into the COVID-19 pandemic in China.

Background: To date, the repeated breakout of the novel coronavirus disease 2019 (COVID-19) pandemic across many regions in China has caused continuous physical and mental harm to health care workers. This study investigates the psychological burden of the pandemic and its associated risk factors among Chinese healthcare workers (HCWs) during a single wave of COVID-19. Methods: For this cross-sectional web-based survey conducted from January 16, 2022 to February 5, 2022, a total of 412 HCWs from Northwestern China were recruited. Their socio-demographic data and COVID-19 related survey variables were then collected using online self-rating questionnaires. In addition, the Chinese versions of well-validated instruments, including the 12-item General Health Questionnaire for psychiatric morbidity, the Generalized Anxiety Disorder Scale-7 for anxiety, the Patient Health Questionnaire-9 for depression and the Insomnia Severity Index-7 for insomnia, were used to assess the participants' mental health status. Multivariate logistic regression analysis was eventually performed to identify the risk factors associated with the psychological outcomes. Results: Of the 388 participants who were included in the final study (94.17% response rate), the prevalence of anxiety, depression, and insomnia symptoms were 25.3% (95% CI: 20.9-29.6%), 40.7% (95% CI: 35.8-45.6%), and 30.9% (95% CI: 26.3-35.5%), respectively. Multivariate logistic regression analysis revealed that being a woman and having a perceived need for psychological support were risk factors for all psychological outcomes, while poor disease cognition and perceived susceptibility were risk factors for anxiety. Poor disease cognition and being unvaccinated against COVID-19 were risk factors for depression, with the latter also being an independent risk factor for insomnia. Conclusion: This study has identified a relatively lower prevalence rate of psychological disorders among Chinese HCWs during a single wave, deeper into the COVID-19 pandemic. Female HCWs, and those who had a perceived need for psychological support, had poor disease cognition, were perceived as susceptible to COVID-19 and had not been vaccinated against COVID-19 deserve more attention.

Novel DIP2C gene splicing variant in an individual with focal infantile epilepsy.

Disco-interacting protein 2 C (DIP2C) encodes a disco-interacting protein and is highly expressed in the nervous system. Most variants of DIP2C are microdeletions on chromosome 10p15.3. This study reports a 17-month-old infant with focal infantile epilepsy who has a single-nucleotide variation in DIP2C that results in alternative splicing. The de novo variation (NM_014974.3: c.1057+2T>G) in DIP2C was uncovered through whole-exome sequencing. Minigene assays were performed and verified the alternative splicing caused by the variation. Finally, an 80-bp nucleotide deletion in the 3' end of Exon 8 was detected. Our study identified a de novo splicing variant that affects the coding length of DIP2C. This finding provides a new candidate gene for focal infantile epilepsy. Importantly, our finding is the first to associate a single nucleotide variant in DIP2C with focal infantile epilepsy.

The clinical features, treatment and outcomes of 33 children from Northwestern China with Anti-N-methyl-D-aspartate receptor encephalitis.

OBJECTIVES: We analyzed the clinical features and outcomes of children with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis in Northwestern China. METHODS: We retrospectively recruited 33 pediatric patients with anti-NMDAR encephalitis in Northwestern China from December 2013 to April 2020. The demographics, clinical features, treatments, and outcomes were reviewed. RESULTS: 33 patients with anti-NMDAR encephalitis were enrolled in this study (a median age of 6.8 years, 20 females and 13 males). The initial symptoms included seizures (42.4%), psychiatric symptoms (39.4%), speech dysfunction (12.1%), and paralysis (6.1%). During the course of the disease, 31 patients (93.9%) presented with psychiatric symptoms, 29 patients (87.9%) presented with speech dysfunction, 25 patients (75.8%) presented with movement disorders and 24 patients (72.7%) presented with sleep disorders followed by seizures, consciousness disturbance, autonomic nervous dysfunction, paralysis, and hypoventilation. 12 patients (36.4%) had abnormal cerebrospinal fluid (CSF) findings, 10 patients (30.3%) exhibited abnormal brain magnetic resonance imaging (MRI) results, and 29 patients (87.9%) showed abnormal Electroencephalography (EEG) findings. None of the patients had tumors. All patients received first-line immunotherapy and 8 patients both received first and second-line immunotherapy. 30 of the 33 patients achieved good outcomes (score on the modified Rankin Scale [mRS] of 0-2), whilst the other 3 patients had poor outcomes (mRS score of 3-6). CONCLUSIONS: Patients with higher CSF anti-NMDAR body titer were more likely to develop sleep disorders, consciousness disturbances and more severe disease states.

Controllable fabrication of polymeric nanowires by NIL technique and self-assembled AAO template for SERS application.

A controllable strategy to fabricate the polymeric nanowires with high throughput and low cost is developed by using the thermal nanoimprint lithography (NIL) technique and self-assembled anodic aluminum oxide (AAO) template. The length of polymeric nanowires can be controlled by adjusting the duration of thermal NIL. A fill mechanism of thermoplastic intermediate polymer stamp (IPS) polymer pressed into the AAO nanopores is closely studied. The as-prepared IPS polymeric nanowire-based Surface-Enhanced Raman Scattering (SERS)-active substrate exhibits a remarkable reproducibility. The effective adsorption of the R6G as probe molecule near to hotspots generated at 3D vertically aligned polymeric nanowire SERS active substrates shows extraordinary enhancement of Raman signal with an enhancement factor (EF) of 105-106. The present strategy is of great guiding significance to broaden the use of thermal NIL technique and AAO template for the fabrication of other nanomaterials, especially for the flexible and transparent polymer-based nanomaterials.

Sterol metabolism and protein metabolism are differentially correlated with sarcopenia in Asian Chinese men and women.

OBJECTIVES: Our aim was to investigate the prevalence and predictive variables of sarcopenia. METHODS: We recruited participants from the Peking Union Medical College Hospital Multicenter Prospective Longitudinal Sarcopenia Study (PPLSS). Muscle mass was quantified using bioimpedance, and muscle function was quantified using grip strength and gait speed. Logistic regression revealed the relationships between sarcopenia and nutritional, lifestyle, disease, psychosocial and physical variables. RESULTS: The prevalence of sarcopenia and sarcopenic obesity was 9.2%-16.2% and 0.26%-9.1%, respectively. Old age, single status, undernourishment, higher income, smoking, low physical activity, poor appetite and low protein diets were significantly associated with sarcopenia. Multiple logistic regression analysis showed that age was a risk factor for all stages of sarcopenia, and participants above 80 years were greater than fivefold more susceptible to sarcopenia, while lower physical activity was an independent risk factor. The optimal cut-off value for age was 71 years, which departs from the commonly accepted cut-off of 60 years. Female participants were greater than twofold less susceptible to sarcopenia than male participants. The sterol derivative 25-hydroxyvitamin D was associated with fourfold lower odds of sarcopenia in male participants. Several protein intake variables were also correlated with sarcopenia. Based on these parameters, we defined a highly predictive index for sarcopenia. CONCLUSIONS: Our findings support a predictive index of sarcopenia, which agglomerates the complex influences that sterol metabolism and nutrition exert on male vs female participants.

Efficacy and Safety of Rituximab in Chinese Children With Refractory Anti-NMDAR Encephalitis.

Purpose: To assess the efficacy and safety of rituximab treatment as second-line immunotherapy in pediatric cases of anti-NMDA receptor (NMDAR) encephalitis. Methods: We retrospectively recruited 8 patients with anti-NMDAR encephalitis who were treated with rituximab as second-line immunotherapy. We evaluated the clinical features, laboratory examination results and treatment protocols of the Chinese children and defined good outcomes based on the modified Rankin scale (mRS) score (0-2) at the last follow-up. Results: A total of eight pediatric patients (median age 6.7 years; four female) with refractory anti-NMDAR encephalitis were recruited to the study. Rituximab was given after a median duration of disease of 57 days (range 50.5-113.75 days). The use of rituximab led to a significant reduction in the mRS and CD19+ B-cells compared to before rituximab infusion (P < 0.05). Five patients (62.5%) had a good outcome (mRS ≤ 2) including four patients (50%) who showed complete recovery (mRS = 0) at the last follow-up. Transient infusion adverse events were recorded in 2 patients (25%). Two patients (25%) had severe infectious adverse events (AEs) and two patients with grade 5 (death). None of the patients developed progressive multifocal leukoencephalopathy (PML). Conclusion: Our study provides evidence that rituximab can efficiently improve the clinical symptoms of anti-NMDAR encephalitis in children. However, due to the risk of adverse infections, rituximab should be restricted in pediatric patients with high rates of mortality and disability.

CRISPR/Cas9-mediated SlAN2 mutants reveal various regulatory models of anthocyanin biosynthesis in tomato plant.

KEY MESSAGE: Combining phenotype and gene expression analysis of the CRISPR/Cas9-induced SlAN2 mutants, we revealed that SlAN2 specifically regulated anthocyanin accumulation in vegetative tissues in purple tomato cultivar 'Indigo Rose.' Anthocyanins play an important role in plant development and also exhibit human health benefits. The tomato genome contains four highly homologous anthocyanin-related R2R3-MYB transcription factors: SlAN2, SlANT1, SlANT1-like, and SlAN2-like/Aft. SlAN2-like/Aft regulates anthocyanin accumulation in the fruit; however, the genetic function of the other three factors remains unclear. To better understand the function of R2R3-MYB transcription factors, we conducted targeted mutagenesis of SlAN2 in the purple tomato cultivar 'Indigo Rose' using clustered regularly interspersed short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9). The SlAN2 mutants had a fruit color and anthocyanin content similar to cv. 'Indigo Rose,' while the anthocyanin content and the relative expression levels of several anthocyanin-related genes in vegetative tissues were significantly lower in the SlAN2 mutant relative to cv. Indigo Rose. Furthermore, we found that anthocyanin biosynthesis is controlled by different regulators between tomato hypocotyls and cotyledons. In addition, SlAN2 mutants were shorter, with smaller and lighter fruits than cv. 'Indigo Rose.' Our findings further our understanding of anthocyanin production in tomato and other plant species.

Impact of ischemia on sample quality of human pancreatic tissues.

BACKGROUND: Successful clinical evaluation of human tumors relies on proper handling of tissue samples to maximally preserve the cellular and metabolic states in vivo. Pancreatic samples are particularly sensitive to sample mishandling due to the abundance of digestive enzymes. We study how the duration of ischemia, in vivo and ex vivo, both of which are unavoidable lagging periods following surgical dissection, significantly impact the utility of pancreatic samples. METHODS: We systematically characterize a wide range of tissue integrity features, including histological patterns, cellular structures, DNA/RNA quality and activity of major signaling pathways in normal pancreases and pancreatic ductal adenocarcinoma (PDAC) tumor tissues from 41 patients with different ischemia. RESULTS: We reveal that tissues experiencing longer periods of ischemia exhibit significant deterioration and could potentially mislead disease diagnosis and preclinical research. Based on these analyses, we propose an optimal procedure that balances better clinical practice and high tissue sample quality. CONCLUSIONS: Our work provides a guideline for pancreatic sample handling and could have wide implications in clinical diagnosis and translational research.

Whole-genome sequencing reveals distinct genetic bases for insulinomas and non-functional pancreatic neuroendocrine tumours: leading to a new classification system.

OBJECTIVE: Insulinomas and non-functional pancreatic neuroendocrine tumours (NF-PanNETs) have distinctive clinical presentations but share similar pathological features. Their genetic bases have not been comprehensively compared. Herein, we used whole-genome/whole-exome sequencing (WGS/WES) to identify genetic differences between insulinomas and NF-PanNETs. DESIGN: The mutational profiles and copy-number variation (CNV) patterns of 211 PanNETs, including 84 insulinomas and 127 NF-PanNETs, were obtained from WGS/WES data provided by Peking Union Medical College Hospital and the International Cancer Genome Consortium. Insulinoma RNA sequencing and immunohistochemistry data were assayed. RESULTS: PanNETs were categorised based on CNV patterns: amplification, copy neutral and deletion. Insulinomas had CNV amplifications and copy neutral and lacked CNV deletions. CNV-neutral insulinomas exhibited an elevated rate of YY1 mutations. In contrast, NF-PanNETs had all three CNV patterns, and NF-PanNETs with CNV deletions had a high rate of loss-of-function mutations of tumour suppressor genes. NF-PanNETs with CNV alterations (amplification and deletion) had an elevated risk of relapse, and additional DAXX/ATRX mutations could predict an increased relapse risk in the first 2-year period. CONCLUSION: These WGS/WES data allowed a comprehensive assessment of genetic differences between insulinomas and NF-PanNETs, reclassifying these tumours into novel molecular subtypes. We also proposed a novel relapse risk stratification system using CNV patterns and DAXX/ATRX mutations.

Anthocyanin Fruit encodes an R2R3-MYB transcription factor, SlAN2-like, activating the transcription of SlMYBATV to fine-tune anthocyanin content in tomato fruit.

Anthocyanin fruit (Aft) and atroviolacea (atv) were characterized in wild tomato and can enhance anthocyanin content in tomato fruit. However, the gene underlying the Aft locus and the mechanism by which Aft and atv act remain largely unknown. In this study, the Aft locus was fine-mapped to an approximately 145-kb interval on chromosome 10, excluding SlAN2 (Solyc10g086250), SlANT1 (Solyc10g086260) and SlANT1-like (Solyc10g086270), which have previously been suggested as candidates. Thus, the R2R3-MYB transcription factor SlAN2-like (Solyc10g086290) was considered the best candidate gene for Aft. The CRISPR/Cas9-mediated SlAN2-like mutants show a much lower accumulation of anthocyanins associated with the downregulation of multiple anthocyanin-related genes compared to the wild-type tomato, indicating that SlAN2-like is responsible for the Aft phenotype. The repressive function of SlMYBATV also was confirmed through the CRISPR/Cas9 approach. A yeast-two-hybrid assay revealed that SlMYBATV interacts with the bHLH protein SlJAF13. Furthermore, yeast-one-hybrid and dual-luciferase transient expression assays showed that Aft directly binds to the SlMYBATV promoter and activates its expression. The results herein provide candidate genes to enhance anthocyanin content in tomato fruit. This research also provides insight into a mechanism involving the Aft-SlMYBATV pathway that fine-tunes anthocyanin accumulation in tomato fruit.

Experimental dataset of nanoporous GaN photoelectrode supported on patterned sapphire substrates for photoelectrochemical water splitting.

GaN is one of the most promising materials for high PEC efficiency to produce clean, renewable hydrogen in an ecofriendly manner (Ebaid et al., 2015; Kamimura et al., 2017; Yang et al., 2018; Ohkawa et al., 2013). Trough assays of nanoporous gallium nitride (GaN) photoelectrode, we recently demonstrated an improved PEC efficiency and photocurrent density of nanoporous GaN photoelectrode by 470% times with respect to planar counterpart (Li et al., 2019). Here, we report original data acquired under UV-visible spectrometer, X-ray diffraction (XRD), room temperature PL measurements and PEC measurements, based on the characterization of different sapphire substrate, different GaN samples and different GaN photoelectrodes. The optical properties and photoelectrochemical properties of the corresponding samples and possible mechanisms are presented, which is freely available (Li et al., 2019). The data can be valuable for researchers interested in photoelectrochemical water splitting, as well as to researchers developing fabrication of nanoporous photoelectrode. For more insight please see the research article "A nanoporous GaN photoelectrode on patterned sapphire substrates for high-efficiency photoelectrochemical water splitting", https://doi.org/10.1016/j.jallcom.2019.06.234.

Fabrication of GaN truncated nanocone array using a pre-deposited metallic nano-hemispheres template for efficient solar water splitting.

The GaN truncated nanocone is an excellent candidate for better photoelectrochemical efficiency than other GaN nanostructures. Here the highly ordered GaN truncated nanocone array was fabricated using a pre-deposited metallic nano-hemispheres template on a wafer scale. The highly ordered profiles of pre-deposited metallic nano-hemispheres template were defined by anodic aluminum oxide (AAO) masks through electron beam evaporation. The formation mechanism for the profiles of nano-hemispheres and GaN truncated nanocones were investigated. The results elucidate that proper selection of AAO parameters enables controllability of desired profiles and depth of Cr nano-hemispheres template, further controllability of desired profiles and depth of the GaN truncated nanocones. The optical and photoelectrochemical characterizations show the substantial improvements in ultraviolet light absorption and photoelectrochemical efficiency with photocurrent density by 300% times with respect to planar counterpart. The presented synthetic strategy will pave the way towards low-cost and mass production of GaN truncated nanocone photoelectrode for efficient photocatalysis.

Circulating factors associated with sarcopenia during ageing and after intensive lifestyle intervention.

BACKGROUND: Ageing, chronic diseases, prolonged inactivity, and inadequate nutrition pose a severe threat to skeletal muscle health and function. To date, experimental evidence suggests that ageing-related subclinical inflammation could be an important causative factor in sarcopenia. Although inflammatory signalling has been implicated in the pathogenesis of experimental animal models of sarcopenia, few studies have surveyed the clinical association between circulating factors and muscle mass in patients before and after lifestyle interventions. In this study, we evaluated whether proinflammatory cytokines are associated with the onset of sarcopenia, which circulating factors are associated with the severity of sarcopenia, and how these factors change after lifestyle interventions in sarcopenic elderly persons. METHODS: A total of 56 elderly subjects (age ≥ 60 years) with sarcopenia and 56 elderly non-sarcopenic subjects, who met entry criteria and had given informed consent, were selected from the Peking Union Medical College Hospital multicentre prospective longitudinal sarcopenia study for testing relevant circulating factors. Thirty-two elderly subjects from the sarcopenic cohort completed a 12 week intensive lifestyle intervention programme with whey supplements (30 g/day) and a personalized resistance training regimen. The levels of proinflammatory cytokines and metabolic hormones, pre-intensive and post-intensive lifestyle interventions, were measured. RESULTS: The sarcopenic group was significantly older (72.05 ± 6.54 years; P < 0.001), more likely to be inactive and female (57.1% of all sarcopenic patients), and had a higher prevalence of type 2 diabetes (16% higher risk). Compared with non-sarcopenic subjects, serum interleukin (IL)-6, IL-18, tumour necrosis factor-α (TNF-α), TNF-like weak inducer of apoptosis (TWEAK), and leptin were significantly higher, while insulin growth factor 1, insulin, and adiponectin were significantly lower in sarcopenic patients (all P < 0.05). Logistic regression analyses revealed that high levels of TNF-α (>11.15 pg/mL) and TWEAK (>1276.48 pg/mL) were associated with a 7.6-fold and 14.3-fold increased risk of sarcopenia, respectively. After adjustment for confounding variables, high levels of TWEAK were still associated with a 13.4-fold increased risk of sarcopenia. Intensive lifestyle interventions led to significant improvements in sarcopenic patients' muscle mass and serum profiles of TWEAK, TNF-α, IL-18, insulin, and adiponectin (all P < 0.05). CONCLUSIONS: High levels of the inflammatory cytokines TWEAK and TNF-α are associated with an increased risk of sarcopenia, while the metabolic hormones insulin growth factor 1, insulin, and adiponectin are associated with a decreased risk of sarcopenia in our Chinese patient cohort. Intensive lifestyle interventions could significantly improve muscle mass, reduce inflammation, and restore metabolic hormone levels in sarcopenic patients. This trial was registered at clinicaltrials.gov as NCT02873676.

Identification of Candidate HY5-Dependent and -Independent Regulators of Anthocyanin Biosynthesis in Tomato.

High quantities of anthocyanins in plants confer potential protective benefits against biotic and abiotic stressors. Studies have shown that the bZIP transcription factor HY5 plays a key role in controlling anthocyanin accumulation in response to light. However, in hy5 mutants, residual anthocyanins have been detected, indicating that other regulators exist to regulate anthocyanin biosynthesis in an HY5-independent manner. Here, we employed the CRISPR/Cas9 (clustered regularly interspersed short palindromic repeats/CRISPR-associated protein 9) system specifically to induce targeted mutagenesis of SlHY5 in the purple tomato cultivar 'Indigo Rose'. The T2 generation of tomato plants homozygous for the null allele of the SlHY5 frameshift mutated by a 1 bp insertion contained a lower anthocyanin content. Transcriptional analysis showed that most of the anthocyanin biosynthesis structural genes and several regulatory genes were down-regulated in the hy5 mutant lines. With transcriptome analyses of the various tissues from hy5 mutant lines, eight candidate transcription factors were identified that may regulate anthocyanin biosynthesis in an HY5-independent manner. These findings deepen our understanding of how light controls anthocyanin accumulation and facilitate the identification of the regulators of anthocyanin biosynthesis in an HY5-independent manner.

Reference ranges and age-related changes of peripheral blood lymphocyte subsets in Chinese healthy adults.

This study was performed to build region-specific reference ranges of peripheral blood lymphocyte subsets for Chinese healthy adults from the young to the elderly and analyze the trends of changes in lymphocyte subsets for evaluating the impact of age on the values. 151 healthy adults aged 19-86 were recruited based on the SENIEUR protocol. Three sets of reference ranges were finally built applicable for the healthy young (19-44 years), middle-aged (45-64 years) and elder adults ([Symbol: see text]65). Comparisons in parameters among the three cohorts showed that a statistically significant increase in CD16CD56+ NK cell was observed between the middle-aged and elder cohorts, whereas for the majority of the parameters, a significant decline was observed between the young and the middle-aged cohorts. Further results showed that inverse correlations were observed between the age and CD19(+) B, CD3(+) T, CD3(+)CD4(+) T, CD4(+)CD45RA(+)CD62L(+) naïve T cell and CD4(+)CD28(+)/CD4(+), while the positive one was identified between the age and the NK cell. These significant changes of the most of immune parameters provided evidence for immunosenescence. Notably, T cell activation markers of CD8(+)CD38(+) and CD8(+)HLA-DR(+) showed reverse trends of association with age, which provides a clue for further researches on the mechanisms underlying the paradoxical clinical presentation of the elder patients.

[Comparison of imaging characteristics of magnetic resonance myocardial delayed enhancement between ischemic and nonischemic myocardial diseases].

OBJECTIVE: To compare the imaging characteristics of magnetic resonance (MR) delayed enhancement between ischemic and nonischemic myocardial diseases. METHODS: We retrospectively analyzed the imaging and clinical characteristics of 25 patients who had MR delayed enhancement. RESULTS: Among the 25 cases, 19 cases were ischemic heart diseases, in which the delayed enhancement was subendocardium, non-transmural or transmural; two cases were hypertrophic cardiomyopathy, in which the delayed enhancement was midwall in the hypertrophic myocardium, strip- and patch-shaped; one case was dilated cardiomyopathy, in which the delayed enhancement was diffuse small midwall spots two cases was restrictive cardiomyopathy, in which the delayed enhancement was located in the area of the subendocardium both of the right and left ventricles; and one case was a mass of the lateral wall of the left ventricle, in which the delayed enhancement with a clumpy shape was shown. CONCLUSIONS: MR myocardial delayed enhancement is not a specific sign of myocardial infarction of ischeminc heart disease. The differentiation of the etiology of the delayed enhancement relies upon both the MR images and the clinical history.

Coronary angiography with dual source computed tomography: initial experience.

OBJECTIVE: To explore the scan technique and image quality of coronary angiography with dual source computed tomography (CT) without oral metoprolol preparation. METHODS: Plain and enhanced dual source CT coronary angiography without oral metoprolol preparation was prospectively performed in 600 patients. Calcium scoring with plain scan images as well as multi-planar reconstruction (MPR), maximum intensity projection (MIP), and volume rendering technique (VRT) reconstruction with enhanced scan images were performed in all cases. The scan technique and post-reconstruction experience was summarized. The image quality was classified as 1 to 4 points, and coronary segments classified according to the American Heart Association standards were evaluated. RESULTS: The average calcium score of the 600 cases was 213.6 +/- 298.7 (0-3,216.5). The average heart rate of the enhanced scan was 82.1 +/- 16.2 (47-139) bpm. The post-reconstruction methods with which coronary segments could be shown as best as possible consisted of single phase reconstruction method, two or more phases supplemented method, and electrocardiogram editing method. Altogether 8,457 coronary segments were evaluated, among which 97.2% were evaluated as point 1, 1.7% point 2, 0.5% point 3, and 0.6% point 4. The coronary segments in 261 cases were completely normal, while 360 segments were diagnosed with < 50% stenosis and 625 segments with > or = 50% stenosis. CONCLUSIONS: Excellent coronary artery image can be obtained with dual source CT in patients with any heart rate without oral metoprolol preparation. Heart rate is not a major source of the artifact, coronary segments can be well shown with single or multiple-phase reconstruction method.

[EGFR and HER2 gene expression status and their correlation in non-small cell lung cancer].

OBJECTIVE: To explore epidermal growth factor receptor (EGFR) and HER2 gene status, to assess the correlation between EGFR and HER2 gene status, and to investigate the role of copy number increase and amplification of EGFR gene and HER2 gene in the tumorigenesis and disease progression of non-small-cell lung cancer. METHODS: Using Path Vysion kit and LSI EGFR SpectrumOrange/CEP7 Spectrum Green probes, EGFR gene and HER2 gene status were evaluated by fluorescence insitu hybridization (FISH) using formalin-fixed, paraffin-embedded samples from 31 patients with non-small-cell lung cancer, including 20 adenocarcinomas, 2 squamous cell carcinomas, 2 large cell carcinoma, 4 bronchoalveolar carcinomas and 3 adenosquamous carcinomas. The correlation between EGFR and HER2 gene status was analyzed. RESULTS: Six of thirty-one carcinomas showed EGFR gene amplification. Of 25 cases without EGFR gene non-amplification, four tetrasomy and 5 polysomy were detected. Overall, 15 out of 31 carcinomas demonstrated either EGFR gene copy number increase or gene amplification (15/31). HER2 gene amplification was seen in 2 of the 31 cases. Four trisomy, one tetrasomy and nine polysomy cases were found in 29 tumors that had no HER2 gene amplification. Overall, 16 of 31 cases showed either HER2 gene copy number increase and/or amplification (16/31). Synchronous EGFR and HER2 gene numerical changes, i.e. gene copy number increase and gene amplification, were found in 12 of 31 cases (12/31), and almost all such patients had either clinical stage III or IV tumor. EGFR gene numerical changes significantly correlated with HER2 gene abnormality (chi(2)(Adj) = 7.3045, P = 0.0069). CONCLUSIONS: EGFR or HER2 copy number increase is much more frequent than gene amplification in no-small-cell lung cancer. Our data based on gene alterations indicate, for the first time, that there is a significant correlation between EGFR alterations and HER2 abnormalities. Both genes are involved in the tumorigenesis and development of lung cancer. EGFR/HER2 dimer is one of the predominant heterodimerization types in lung cancer. The interactions between EGFR and HER2 may play a rule in the progression of non-small-cell lung cancer.