OBJECTIVE: To explore the clinical characteristics and genetic etiology of a patient with adolescent-onset hypomyelinated leukodystrophy with atrophy of basal ganglia and cerebellum (H-ABC). METHODS: A patient who was diagnosed with H-ABC in March 2018 at the First Affiliated Hospital of Nanjing Medical University was selected as the study subject. Clinical data was collected. Peripheral venous blood samples of the patient and his parents were collected. The patient was subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. RESULTS: The patient, a 31-year-old male, had manifested with developmental retardation, cognitive decline and abnormal gait. WES revealed that he has harbored a heterozygous c.286G>A variant of the TUBB4A gene. Sanger sequencing confirmed that neither of his parents has carried the same variant. Analysis with SIFT online software indicated the amino acid encoded by this variant is highly conserved among various species. This variant has been recorded by the Human Gene Mutation Database (HGMD) with a low population frequency. The 3D structure constructed by PyMOL software showed that the variant has a harmful effect on the structure and function of the protein. According to the guidelines formulated by the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic. CONCLUSION The c.286G>A (p.Gly96Arg) variant of the TUBB4A gene probably underlay the hypomyelinating leukodystrophy with atrophy of basal ganglia and cerebellum in this patient. Above finding has enriched the spectrum of TUBB4A gene variants and enabled early definitive diagnosis of this disorder.
Male ; Humans ; Adolescent ; Adult ; Magnetic Resonance Imaging ; Basal Ganglia/pathology* ; Cerebellum ; Atrophy/pathology* ; Mutation ; Tubulin/genetics*

Active exploratory behaviors have often been associated with theta oscillations in rodents, while theta oscillations during active exploration in non-human primates are still not well understood. We recorded neural activities in the frontal eye field (FEF) and V4 simultaneously when monkeys performed a free-gaze visual search task. Saccades were strongly phase-locked to theta oscillations of V4 and FEF local field potentials, and the phase-locking was dependent on saccade direction. The spiking probability of V4 and FEF units was significantly modulated by the theta phase in addition to the time-locked modulation associated with the evoked response. V4 and FEF units showed significantly stronger responses following saccades initiated at their preferred phases. Granger causality and ridge regression analysis showed modulatory effects of theta oscillations on saccade timing. Together, our study suggests phase-locking of saccades to the theta modulation of neural activity in visual and oculomotor cortical areas, in addition to the theta phase locking caused by saccade-triggered responses.
Animals ; Frontal Lobe/physiology* ; Macaca mulatta ; Neurons/physiology* ; Saccades ; Theta Rhythm ; Visual Fields

"The Expert Group on Tumor Ablation Therapy of Chinese Medical Doctor Association, The Tumor Ablation Committee of Chinese College of Interventionalists, The Society of Tumor Ablation Therapy of Chinese Anti-Cancer Association and The Ablation Expert Committee of the Chinese Society of Clinical Oncology" have organized multidisciplinary experts to formulate the consensus for thermal ablation of pulmonary subsolid nodules or ground-glass nodule (GGN). The expert consensus reviews current literatures and provides clinical practices for thermal ablation of GGN. The main contents include: (1) clinical evaluation of GGN, (2) procedures, indications, contraindications, outcomes evaluation and related complications of thermal ablation for GGN and (3) future development directions.
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Objective:To investigate the therapeutic effects of antibiotic articular cement spacer on shoulder joint infection in the elderly patients during stage-one operation.Methods:The data of 3 patients were analyzed retrospectively who had been treated at Department of Orthopaedics, The Sixth People's Hospital Affiliated to Shanghai Jiao Tong University for shoulder infection from May 2018 to December 2019. They were one man and 2 women with an average age of 65.3 years (from 64 to 67 years). One case of infection followed shoulder puncture, another proximal humeral fracture and another shoulder prosthesis replacement. All the 3 patients underwent radical debridement and implantation of antibiotic shoulder cement spacer in stage-one operation but no stage-two operation. The therapeutic effects were evaluated by American Shoulder and Elbow Surgeons (ASES) scoring, Quick Disabilities of the Arm, Shoulder, and Hand (Quick-DASH) scoring, Visual Analog Scale (VAS), and range of shoulder motion.Results:The 3 patients were followed up for 18 to 28 months (mean, 22.7 months). There was no recurrence of infection and the spacers were in good position. The microorganisms detected were Bifidobacterium brevis in one case and methicillin-resistant Staphylococcus aureus in 2 cases. At the final follow-up, the ASES scores averaged 54.4 (from 46.3 to 60.0), Quick-DASH scores 45.1 (from 40.8 to 50.0), VAS scores 2.3 (from 2 to 3), ranges of elevation 65.7 °, ranges of abduction 43.8° and ranges of external rotation 21.7°.Conclusion:For the elderly patients with shoulder infection, implantation of antibiotic shoulder cement spacer after radical debridement can well control infection, relieve pain and improve shoulder functions, sparing them secondary operation.

Objective:To explore the feasibility in evaluating segmental extracellular volume (ECV) using dual-layer spectral detector CT in patients with heart failure with various percentages of delayed hyper-enhanced volume, using MRI as a reference.Methods:Twenty-seven patients with heart failure in Peking Union Medical College Hospital were prospectively enrolled in this study from July 2019 to January 2021. All the patients underwent both CT late iodine enhancement and MR late gadolinium enhancement imaging within a week. According to percentages of hyper-enhanced volume on cardiac MR image, myocardial segments were classified into 3 groups: 0-4% (group A), 5%-49% (group B) and 50%-100% (group C). ECV images were independently observed by 2 experienced radiologists. The correlation and agreement between CT-ECV and MRI-ECV for the whole myocardial assessment and for the segmental assessment were evaluated using Spearman correlation and Bland-Altman analysis. Inter-observer agreement was assessed using the ICC.Results:Of the 27 patients, 432 segments were analyzed, with 199 segments in group A, 151 segments in group B and 82 segments in group C. In the whole myocardial analysis, the CT-ECV and MRI-ECV were 32.25% (28.04%, 34.28%) and 32.27% (28.35%, 34.77%), respectively. A good correlation was found between CT-ECV and MRI-ECV ( r=0.969, P<0.001). Bland-Altman analysis between CT-ECV and MRI-ECV showed a small bias (0.4%), with 95% limits of agreement of -6.9% to 7.8%. as for the segmental myocardial assessment, the CT-ECV was 28.23% (26.18%, 29.92%) for group A, 33.29% (30.16%, 35.96%) for group B and 40.22% (34.06%, 46.70%) for group C. There was statistically significant difference in ECV among three groups (all P<0.001). Good correlations between CT-ECV and MRI-ECV were found in group A ( r=0.614, P<0.001), group B ( r=0.852, P<0.001) and group C ( r=0.953, P<0.001). Bland-Altman analysis between CT-ECV and MRI-ECV showed a small bias 2.0% (95% limits of agreement:-17.6%-21.6%) in group A, a small bias -0.4% (95% limits of agreement: -13.8%-12.9%) in group B and a small bias -1.8% (95% limits of agreement: -17.4%-13.9%) in group C. The ICC values between 2 observers were 0.877 and 0.945 on CT-ECV and MRI-ECV, respectively. Conclusions:The larger percentage of hyper-enhanced volume on cardiac MR image, the stronger correlation are between the CT-ECV and MRI-ECV. CT-ECV may be taken as an alternative tool for quantitative evaluation of myocardial tissue in patients with heart failure.

Objective:To evaluate the feasibility of high concentrated contrast media combined with monochromatic images to improve image quality with double low scanning in dual-layer spectral coronary CT angiography.Methods:Fifty-six patients with suspected coronary artery disease were enrolled and randomly separated into two groups. All patients were scanned at 120 kVp in step-and-shoot mode using a dual-layer detector CT (IQon spectral CT). Patients were either injected with 18 ml high concentration contrast medium(400 mgl/ml) at 2 ml/s (group A) or 45 ml contrast medium (370 mgl/ml) at 4 ml/s (group B). Forty to 80 keV monoenergetic images with 10 keV increment and conventional image (group A2) were reconstructed for group A, conventional poly-energetic image was reconstructed for group B. Region of interest was placed on aorta root (AO), middle segment of left anterior descending (LAD), left circumflex (LCX) and right coronary artery (RCA) to measure the attenuation and noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). Image quality was assessed by two reviewers independently with a 4-point scale on image quality (1-undiagnostic,4-excellent). The objective and subjective image evaluation were compared using the Kruskal-Wallis test. The Steel Dwass was used for multiple comparisons between monoenergetic images in Group A and conventional images in Group B, after the Kruskal-Wallis test.Results:There were significant differences among the attenuation, noise, SNR and CNR of group B, group A2, and monoenergetic images(all P<0.001).The CT value in the aortic root was significantly higher at 40-50 keV monoenergetic images than that in group B(all P<0.05), and similarly, the CT value in LAD,LCX and RCA at 40 keV were superior than that in group B(all P<0.001). There was no significant difference in the noise of the aortic root among 40 keV image, group A2 and group B(all P>0.05),while the noise in the 50-80 keV monoenergetic images were significantly lower than that in Group B(all P<0.001). The SNR and CNR in the aortic root were significantly higher at 40-60 keV monoenergetic images than that in group B(all P<0.001).The SNR in LAD and RCA at 40，50 keV and the CNR in LAD and RCA at 40-60 keV were higher than that in group B(all P<0.01).The SNR at 40-60 keV and CNR at 40-70 keV in LCX were superior than that in group B(all P<0.05). There were significant differences among the subjective image quality score of group B, group A2, and monoenergetic images(all P<0.001).The subjective image quality score of 40，50 keV images were not significantly different from that in group B (all P>0.05),while the score in 60-80 keV image and group A2 were lower than that of Group B(all P<0.001). Conclusion:40，50 keV low monochromatic images derived from dual-layer spectral detect CT combined with high concentrated contrast media can provide comparable or superior image quality with double low scanning in CCTA study.

Objective To analyze the expression and role of ubiquitin specific peptidase 18 (USP18) in gastric cancer cells,and to investigate the relationship between the development of gastric cancer and USP18.Methods The levels of USP18 protein and mRNA expression in immortalized gastric mucosa epithelial GSE cell lines and gastric cancer cell lines (AGS,MKN45,MKN25,BGC823,BGC803,SGC7901) were detected by using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot,respectively.The role of USP18 in the invasion and proliferation of gastric cancer cells was analyzed by using CCK8 and Transwell assays.Results The mRNA level of USP18 was lower in GSE cell lines than that in gastric cancer cells (F =794.052,P ＜ 0.000 1).In six gastric cancer cell lines,mRNA level of USP18 was relatively high in BGC823 (17.62±0.55) and BGC803 (13.52±0.50) cell lines,and low in MKN28 (1.40±0.17) and MKN45 cell lines (4.23±0.26).As for the protein level,the expression of USP18 was lowest in GSE cell line.In six gastric cancer cell lines,the expression of USP18 was the highest in more aggressive SGC7901 and BGC803 cell lines and the lowest in AGS and MKN45 cells.Compared with the control group,interference of USP18 decreased the invasion and proliferation abilities of SGC7901 and BGC803 cell lines (P ＜ 0.01).Conclusion USP18 is highly expressed in more invasive gastric cancer cells,and the downregulation of USP18 can suppress the invasion and proliferation of gastric cancer cells.

Cells can adapt to environment and development by reconstructing their transcriptional networks to regulate diverse cellular processes without altering the underlying DNA sequences. These alterations, namely epigenetic changes, occur during cell division, differentiation and cell death. Numerous evidences demonstrate that epigenetic changes are governed by various types of determinants, including DNA methylation patterns, histone posttranslational modification signatures, histone variants, chromatin remodeling, and recently discovered chromosome conformation characteristics and non-coding RNAs (ncRNAs). Here, we highlight recent efforts on how the two latter epigenetic factors participate in the sophisticated transcriptional process and describe emerging techniques which permit us to uncover and gain insights into the fascinating genomic regulation.
Cell Death ; Cell Differentiation ; Cell Division ; Chromatin ; chemistry ; metabolism ; Chromatin Assembly and Disassembly ; DNA Methylation ; Epigenesis, Genetic ; Eukaryotic Cells ; cytology ; metabolism ; Histones ; genetics ; metabolism ; Humans ; Protein Processing, Post-Translational ; RNA, Untranslated ; genetics ; metabolism ; Transcription, Genetic

This study aimed to investigate infiltration related microRNAs (miRNAs) in bladder urothelial carcinoma (BUC). Twenty patients with BUC were enrolled and divided into 2 groups according to infiltration or not: infiltrating BUC group (n=12) and non-infiltrating BUC group (n=8). Gene chip was used to detect infiltration related miRNAs in the BUC samples. In other recruited 17 patients with BUC who were divided into infiltrating BUC samples (n=14) and non-infiltrating BUC samples (n=3), and in 4 BUC cell lines (EJ, 5637, T24 and BIU-87), the expression of miRNAs was assayed by using reverse transcription-polymerase chain reaction (RT-PCR). In infiltrating BUC group, as compared with non-infiltrating BUC group, there were 7 differentially expressed miRNAs: hsa-miR-29c, hsa-miR-200a, hsa-miR-378, hsa-miR-429, hsa-miR-200c and hsa-miR-141 were up-regulated, while hsa-miR-451 was down-regulated. In the BUC samples, the results of RT-PCR were consistent with those by the miRNA array. In the cancer cell lines, RT-PCR in T24 only revealed the similar expression pattern of miRNAs to that by the miRNA array. It is suggested that infiltration of BUC is related with different expression of miRNAs, which may provide a novel platform for further study on function and action mechanism of miRNAs.
Carcinoma ; genetics ; Cell Line, Tumor ; Humans ; MicroRNAs ; genetics ; Urinary Bladder ; metabolism ; Urinary Bladder Neoplasms ; genetics

Objective To figure out and verify infiltration related miRNAs in bladder urothelial carcinoma (BUC). Methods Fresh tissues (20 samples,12 were infiltrative BUC samples,8 were non-infiltrative BUC samples) were collected in liquid nitrogen.The total RNA was extracted by using Trizol reagents.RNA quality control; miRNA microarray hybridization; data analysis.Another 22 samples were collected in fresh (15 were infiltrative BUC samples,7 were non-infiltrative BUC samples) for verifying purpose.4 types of bladder cancer cell lines were used for the study.BUC cell strain; total RNA was extracted by Trizol reagents; RNA quality control; RT-PCR and analysis of the data. Results ①In infiltrative BUC group,compared with non-infiltrative BUC group,there were 7 differentially expressed miRNAs:hsa-miR29c,hsa-miR-200a,hsa-miR-378,hsa-miR-429,hsa-miR-200c and hsa-miR-141 were up-regulated; hsamiR-451 was down-regulated.②In collected samples,the result of RT-PCR was consistent with miRNA array.③In bladder cancer cell lines,only the results of T24 were consistent with miRNA array. Conclusion Infiltration of BUC might relate with different expression of miRNAs.