Objective Linkage analysis were performed in 2 pure Chinese paroxysmal kinesigenic dyskinesia families to localize the locus of them. Method Microsatellites markers corresponding to pericentrometric region of chromosome 16 were used in parametric and nonparametrie linkage analysis for 27 members in the 2 pedigrees, haplotypes were constructed subsequently. Result The maximum LOD score and NPL score in the 2 families were all negative, P values were significantly larger than 0.05.No haplotype segregated with PKD phenotype was found. It showed no evidence of association with known PKD loci in both pedigrees, providing evidence for a novel PKD locus. Conclusion PKD is heterogeneous, a novel PKD locus may be in pure Chinese pedigrees.

Objective To determine the methylation level of P15INK4B gene promoter in different types of myelodysplastic syndromes (MDS) and its correlation with its prognosis.Methods Methylation frequency of the P15INK4B gene promoter in 44 cases of MDS were determined by methylation-specific polymerase chain reaction (PCR) and pyrosequencing,and its correlation with clinical classification and characteristics of MDS were statistically analyzed.Results Frequency of P15INK4B gene promoter methylation in myelodysplastic syndromes-refractory anemia with excess blasts Ⅱ (MDS-RAEB Ⅱ) patients was (46.89 ± 15.41) ％,significandy higher than that in other types of MDS (P ＜ 0.05),but no difference in promoter methylation frequency was detected among the other types of MDS (P ＞ 0.05) ; frequency of P15INK4B gene promoter methylation was found to be correlated with decline in platelet upon diagnosis (t =9.02,P ＜ 0.01),but showed no significant correlation with drop of hemoglobin or leukopenia (P ＞0.05).As for the correlation between P15INK4B gene promoter methylation and MDS risk stratification,no significant difference was detected between the low-risk and very low-risk groups (P ＞ 0.05),but significant differences were detected among the medium-risk,high-risk,and very high-risk groups (P ＜ 0.05).In addition,frequency of P15INK4B gene promoter methylation was (49.21 ± 8.78)％ in MDS patients that developed leukemia in the following two year,significantly higher than that in MDS patients who didn't (19.64 ± 6.24) ％ (P ＜ 0.05).Conclusions P15INK4B gene promoter methylation frequency is a valuable indicator of prognosis of MDS patients.

Objective:To evaluate the left ventricular myocardial work parameters of the animal models with left bundle branch block (LBBB) and evaluate the effects of LBBB on left ventricular function and motion pattern by pressure-strain loops (PSL) of speckle tracking imaging (STI).Methods:In Twenty-four healthy male beagles, LBBB was induced by radio frequency ablation under anesthesia, and blood pressure was measured at the same time. Electrocardiograms and echocardiography images were acquired before (baseline), 30 minutes after (acute-LBBB) and 3 months after(chronic-LBBB) the creation of LBBB respectively. STI was applied to measure the left ventricular global longitudinal strain (GLS) and obtain the the PSL of each time point to evaluate the left ventricular global and segmental myocardial work parameters.Results:Compared to the baseline, the global work efficiencies(GWE) were obviously reduced ( P<0.05) and global wasted works(GWW) were significantly increased ( P<0.01) in the acute-LBBB and chronic-LBBB, significant differences were observed in GLS between acute-LBBB and baseline( P=0.04). In baseline, the work efficiency (WEsept) and the constructive work (CWsept) in the basal and middle segments of the septal wall were both obviously higher than the corresponding segments of left ventricular lateral wall( P<0.01), while the distribution of the wasted work(WWsept) was opposite( P<0.01). In acute-LBBB, the WEsept of all segments were significantly decreased ( P<0.05), the WWsept were obviously increased( P<0.05), the CWsept of basal segment was significantly reduced( P=0.01), while the wasted work in the basal segment of lateral wall(WWlat) was increased( P=0.04) compared with the baseline. Compared with the acute-LBBB, the WEsept of basal and middle segments were mildly recovery( P=0.03) in chronic-LBBB, but were still lower than the baseline ( P=0.001), the changes of the other myocardial work parameters of septal and lateral wall were similar to the acute-LBBB. Conclusions:Both acute-LBBB and chronic-LBBB can lead to the changes of left ventricular global and segmental myocardial work parameters. The myocardial work parameters of left ventricle can quantitatively analyze the changes of left ventricular function and motion pattern of the LBBB.

Objective:To explore whether the simulation training system for transesophageal echocardiography (TEE) can improve the effectiveness of standardized training of resident anesthesiologists.Methods:A total of 72 resident anesthesiologists without experience in cardiac ultrasound were randomly divided into traditional teaching group (36 residents) and simulation training group (36 residents). Before and after the teaching, theoretical examinations of 5 knowledge points related to cardiac ultrasound were conducted. After a standardized rotation of 2 months, the students were re-examined for both theories and operations, and clinical indicators were recorded. SPSS 23.0 was used for the t-test, rank sum test, chi-square test, or Fisher's exact test. Results:There was no significant difference in scores of theoretical examinations between the two groups of students before teaching. After teaching, the scores of the simulation training group were higher than those of the traditional teaching group, and the differences were significant in cross-sectional recognition and image diagnosis ( P<0.05). After rotation, there was no significant difference in theoretical examination between the two groups of students, but the score of operation was significantly higher in the simulation training group than in the traditional teaching group ( P<0.05). During the rotation period, the incidence of TEE-related complications was relatively low and the quantitative score of clinical operational skill assessment was relatively high in the simulation training group ( P<0.05). Conclusion:Anesthesia residents who receive training with the simulation system before TEE training can quickly acquire operational skills, reduce related complications, and more accurately identify and obtain standard TEE sections, which has significant value for clinical teaching.

Objective:To analyze the long-term prognosis and prognostic factors of allergic bronchopulmonary aspergillosis(ABPA) in children suffering from cystic fibrosis (CF).Methods:An observational study was performed.All children who were admitted to the Department of Respiratory, Beijing Children′s Hospital, Capital Medical University from August 2014 to June 2018, with more than 2 years of followed up for the diagnosis of CF accompanied by ABPA were involved.Results:Three children met the inclusion criteria, with 2 boys and 1 girl, and their diagnostic age were 14, 8 and 9 years old, respectively.The follow-up duration ranged from 2 to 6 years.All the 3 cases were treated with systemic corticosteroids and antifungal agent.In case 1, the initial dose of prednisone was 0.75 mg/(kg·d), and the course of treatment was more than 5 years.The corticosteroid-dependent patient suffered from expectoration and chest pain, and radiographic findings indicated exacerbation, while his lung function was normal.Treating with initial dose of prednisone 2 mg/(kg·d) for 9 months, case 2 had normal serum immunoglobulin E(IgE) concentration, but his pulmonary artery was infiltrated by lesions, thus leasing to lobectomy.In case 3, the initial dose of prednisone was 0.6 mg/(kg·d), and the course of treatment was 18 months.And she developed persistent hypoxemia, and decreased pulmonary function, so lung transplantation was necessary 2 years after diagnosis.Conclusions:Systemic glucocorticoid combined with antifungal therapy is the main treatment for CF with ABPA, but there are individual differences in the efficacy.The level of serum total IgE is not always consistent with lung function and chest images.The overall prognosis is poor, and it is infeasible to evaluate the prognosis by single factor.

The widespread application of next generation sequencing (NGS) in clinical settings has enabled testing, diagnosis, treatment and prevention of genetic diseases. However, many issues have arisen in the meanwhile. One of the most pressing issues is the lack of standards for reporting genetic test results across different service providers. The First Forum on Standards and Specifications for Clinical Genetic Testing was held to address the issue in Shenzhen, China, on October 28, 2017. Participants, including geneticists, clinicians, and representatives of genetic testing service providers, discussed problems of clinical genetic testing services across in China and shared opinions on principles, challenges, and standards for reporting clinical genetic test results. Here we summarize expert opinions presented at the seminar and report the consensus, which will serve as a basis for the development of standards and guidelines for reporting of clinical genetic testing results, in order to promote the standardization and regulation of genetic testing services in China.

OBJECTIVES: Platelet-to-lymphocyte ratio (PLR) has recently been investigated as a new inflammatory marker in many inflammatory diseases, including systemic lupus erythematosus and immunoglobulin A vasculitis. However, there were very few reports regarding the clinical role of PLR in patients with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis. This study was thus undertaken to investigate the relationship between inflammatory response and disease activity in Chinese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA) associated vasculitis. Furthermore, we evaluated whether PLR predicts the progression of end stage of renal disease (ESRD) and all-cause mortality. METHODS: The clinical, laboratory and pathological data, and the outcomes of MPO-ANCA associated vasculitis patients were collected. The Spearman correlation coefficient was computed to examine the association between 2 continuous variables. Cox regression analysis was used to estimate the association between PLR and ESRD or all-cause mortality. RESULTS: A total of 190 consecutive patients with MPO-ANCA associated vasculitis were included in this study. Baseline PLR was positively correlated with CRP (r=0.333, P<0.001) and ESR (r=0.218, P=0.003). PLR had no obvious correlation with Birmingham Vasculitis Activity Score (BVAS). Patients having PLR≥330 exhibited better cumulative renal survival rates than those having PLR<330 (P=0.017). However, there was no significant difference in the cumulative patient survival rates between patients with PLR≥330 and those with PLR<330 at diagnosis (P>0.05). In multivariate analysis, PLR is associated with the decreased risk of ESRD (P=0.038, HR=0.518, 95% CI 0.278 to 0.963). We did not find an association between PLR with all-cause mortality using multivariate analysis (HR=1.081, 95% CI 0.591 to 1.976, P=0.801). CONCLUSIONS PLR is positively correlated with CRP and ESR. Furthermore, PLR may independently predict the risk of ESRD.
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis* ; Antibodies, Antineutrophil Cytoplasmic/analysis* ; China/epidemiology* ; Humans ; Kidney Failure, Chronic/complications* ; Lymphocytes ; Peroxidase ; Retrospective Studies

BACKGROUND: Ischemic acute kidney injury (AKI) is a common syndrome associated with considerable mortality and healthcare costs. Up to now, the underlying pathogenesis of ischemic AKI remains incompletely understood, and specific strategies for early diagnosis and treatment of ischemic AKI are still lacking. Here, this study aimed to define the transcriptomic landscape of AKI patients through single-cell RNA sequencing (scRNA-seq) analysis in kidneys. METHODS: In this study, scRNA-seq technology was applied to kidneys from two ischemic AKI patients, and three human public scRNA-seq datasets were collected as controls. Differentially expressed genes (DEGs) and cell clusters of kidneys were determined. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, as well as the ligand-receptor interaction between cells, were performed. We also validated several DEGs expression in kidneys from human ischemic AKI and ischemia/reperfusion (I/R) injury induced AKI mice through immunohistochemistry staining. RESULTS: 15 distinct cell clusters were determined in kidney from subjects of ischemic AKI and control. The injured proximal tubules (PT) displayed a proapoptotic and proinflammatory phenotype. PT cells of ischemic AKI had up-regulation of novel pro-apoptotic genes including USP47 , RASSF4 , EBAG9 , IER3 , SASH1 , SEPTIN7 , and NUB1 , which have not been reported in ischemic AKI previously. Several hub genes were validated in kidneys from human AKI and renal I/R injury mice, respectively. Furthermore, PT highly expressed DEGs enriched in endoplasmic reticulum stress, autophagy, and retinoic acid-inducible gene I (RIG-I) signaling. DEGs overexpressed in other tubular cells were primarily enriched in nucleotide-binding and oligomerization domain (NOD)-like receptor signaling, estrogen signaling, interleukin (IL)-12 signaling, and IL-17 signaling. Overexpressed genes in kidney-resident immune cells including macrophages, natural killer T (NKT) cells, monocytes, and dendritic cells were associated with leukocyte activation, chemotaxis, cell adhesion, and complement activation. In addition, the ligand-receptor interactions analysis revealed prominent communications between macrophages and monocytes with other cells in the process of ischemic AKI. CONCLUSION Together, this study reveals distinct cell-specific transcriptomic atlas of kidney in ischemic AKI patients, altered signaling pathways, and potential cell-cell crosstalk in the development of AKI. These data reveal new insights into the pathogenesis and potential therapeutic strategies in ischemic AKI.
Humans ; Mice ; Animals ; Transcriptome/genetics* ; Ligands ; Kidney/metabolism* ; Acute Kidney Injury/metabolism* ; Ischemia/metabolism* ; Reperfusion Injury/metabolism* ; Sequence Analysis, RNA ; Adaptor Proteins, Signal Transducing/metabolism* ; Tumor Suppressor Proteins/metabolism*