[Chylomicron retention disease caused by SAR1B gene variations in 2 cases and literatures review].

Objective: To summarize the genotype and clinical characteristics of chylomicron retention disease (CMRD) caused by secretion associated Ras related GTPase 1B (SAR1B) gene variations. Methods: Clinical data and genetic testing results of 2 children with CMRD treated at Children's Hospital of Fudan University and Jiangxi Provincial Children's Hospital from May 2022 to July 2023 were summarized. To provide an overview of the clinical and genetic characteristics of CMRD caused by SAR1B gene variations, all of the literature was searched and reviewed from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, China VIP database, China Biology Medicine disc and PubMed database (up to January 2024) with "chylomicron retention disease" "Anderson disease" or "Anderson syndrome" as the search terms. All relevant literatures were reviewed to summarize the clinical and genetic features of CMRD caused by SAR1B gene variations. Results: One 11-year-old boy and one 4-month-old girl with CMRD. Both patients had lipid malabsorption, failure to thrive, decreased cholesterol, elevated transaminase and creatine kinase, and Vitamin E deficiency, with homozygous variations (c.224A>G) and compound heterozygous variations (c.224A>G and c.554G>T) in SAR1B gene, respectively. Case 1 was followed up for over a month, and he still occasionally experienced lower limb muscle pain. Case 2 was followed up for more than a year, and her had caught up to normal levels. Both patients had no other significant discomfort. Literature search retrieved 0 Chinese literature and 22 English literatures. In addition to the 2 cases reported in this study, a total of 51 patients were identified as CMRD caused by SAR1B gene variations. Twenty-one types of SAR1B variants 10 missense, 4 nonsense, 3 frameshift, 1 in-frame deletion, 1 splice, 1 gross deletion, and 1 gross insertion-deletion were found among the 51 CMRD cases. Among all the patients, 49 cases had lipid malabsorption (43 cases had diarrhea or fatty diarrhea, 17 cases had vomiting, and 12 cases had abdominal distension), 45 cases had lipid soluble Vitamin deficiency (43 cases had Vitamin E deficiency, 10 cases had Vitamin A deficiency, 9 case had Vitamin D deficiency, and 5 cases had Vitamin K deficiency), 35 cases had failure to thrive, 32 cases had liver involvement (32 cases had elevated transaminases, 5 cases had fatty liver, and 3 cases had hepatomegaly), 29 cases had white small intestinal mucosa under endoscopy, and 17 cases had elevated creatine kinase, 14 cases had neuropathy, 5 cases had ocular lesions, 2 cases had acanthocytosis, 1 case had decreased cardiac ejection fraction, and 1 case was symptom-free. Conclusions: Early infancy failure to thrive and lipid malabsorption are common issues for CMRD patients. The laboratory tests are characterized by hypocholesterolemia with or without fat-soluble Vitamin deficiency, elevated liver enzymes and (or) creatine kinase. Currently, missense variations are frequent among the primarily homozygous SAR1B genotypes that have been described.

[Short-term efficacy and safety of cardiac contractility modulation in patients with heart failure].

Objective: To investigate the short-term efficacy and safety of cardiac contractility modulation (CCM) in patients with heart failure. Methods: This was a cross-sectional study of patients with heart failure who underwent CCM placement at the First Affiliated Hospital of Xinjiang Medical University from February to June 2022. With a follow-up of 3 months, CCM sensation, impedance, percent output, and work time were monitored, and patients were compared with pre-and 3-month postoperative left ventricular ejection fraction (LVEF) values, and 6-minute walk test distance and New York Heart Association (NYHA) cardiac function classification, and the occurrence of complications was recorded. Results: CCM was successfully implanted in all 9 patients. Seven(7/9) of them were male, aged (56±14) years, 3 patients had ischaemic cardiomyopathy and 6 patients had dilated cardiomyopathy. At 3-month postoperative follow-up, threshold was stable, sense was significantly lower at follow-up than before (right ventricle: (16.3±7.0) mV vs. (8.2±1.1) mV, P<0.05; local sense: (15.7±4.9) mV vs. (6.7±2.5) mV, P<0.05), and impedance was significantly lower at follow-up than before (right ventricle (846±179) Ω vs. (470±65) Ω, P<0.05, local sense: (832±246) Ω vs. (464±63) Ω, P<0.05). The CCM output percentage was (86.9±10.7) %, the output amplitude was (6.7±0.4) V, and the daily operating time was (8.6±1.0) h. LVEF was elevated compared to preoperative ((29.4±5.2) % vs. (38.3±4.3) %, P<0.05), the 6-minute walk test was significantly longer than before ((96.8±66.7)m vs. (289.3±121.7)m, P<0.05). No significant increase in the number of NYHA Class Ⅲ-Ⅳ patients was seen (7/9 vs. 2/9, P>0.05). The patient was not re-hospitalised for worsening heart failure symptoms, had no malignant arrhythmic events and experienced significant relief of symptoms such as chest tightness and shortness of breath. No postoperative complications related to pocket hematoma, pocket infection and rupture, electrode detachment, valve function impairment, pericardial effusion, or cardiac perforation were found. Conclusions: CCM has better short-term safety and efficacy in patients with heart failure.

Advances in non-pharmacological management of Parkinson's disease complicated with blood pressure abnormalities.

Parkinson's disease (PD) often presents with autonomic dysregulation, leading to blood pressure irregularities such as neurogenic orthostatic hypotension (nOH), neurogenic supine hypertension (nSH), and postprandial hypotension (PPH). Unfortunately, these conditions remain prevalent and receive insufficient attention in scientific discourse. They not only cause complications like syncope, falls, and fractures but also result in long-term damage to vital organs, diminishing patients' quality of life. Early implementation of appropriate non-pharmacologic management is crucial to prevent severe adverse events later on. This review focuses on the types, clinical characteristics, mechanisms, and common non-pharmacologic management measures for PD complicated by abnormal blood pressure. By promoting early diagnosis, recognizing symptoms of abnormal blood pressure, and employing non-pharmacologic interventions such as health education, dietary adjustments, exercise, and Chinese medicine techniques, we aim to improve patients' symptoms and quality of life while providing practical guidance for managing PD-related blood pressure abnormalities.

[Incidence and risk factors of congenital ventricular septal defect in Qingdao].

Objective: To analyze the incidence and risk factors of ventricular septal defect (VSD) in Qingdao. Methods: A prospective cohort study design was used to include pregnant women who underwent prenatal screening in Qingdao between August 2018 and June 2020 (the whole population coverage). VSD was diagnosed according to the pulse oxygen saturation and heart auscultation, and the final diagnosis was made according to the echocardiography of VSD positive newborns within postnatal day 7. Results: The study included 115 238 live births, among which 388 were diagnosed as VSD, with an incidence of 3.37‰. The results of multivariate logistic regression analysis showed that mother with postgraduate level (OR=1.61, 95%CI: 1.00-2.58, P=0.049) (compared with junior high school and below), preterm birth history (OR=2.90, 95%CI: 1.47-5.70, P=0.002), and pregnancy history of congenital heart disease (OR=5.98, 95%CI: 2.63-14.73, P<0.001) were risk factors for VSD. Compared with female infants, the overall risk of VSD in male infants was relatively low (OR=0.74, 95%CI: 0.60-0.91, P=0.005). Conclusions: The incidence of VSD in Qingdao is 3.37‰. The risk factors of VSD include higher maternal education level, pregnancy history of congenital heart disease and preterm birth history. Moreover, the overall risk of VSD in male infants is low.

[Analysis of factors related to systemic embolism in patients≥75 years old with non-valvular atrial fibrillation].

Objective: To explore the related risk factors for systemic embolism (SE) in patients aged≥75 years with non-valvular atrial fibrillation (NVAF). Methods: A case-control study. NVAF patients aged≥75 years who were hospitalized at the First Affiliated Hospital of Xinjiang Medical University from October 2018 to October 2020 were divided into no SE (n=1 127) and SE (n=433) groups according to the occurrence of SE after NVAF. Multivariate logistic regression was used to analyze SE-related factors in patients with NVAF without anticoagulation treatment. Results: In the multivariate model, the following factors were associated with an increased risk of SE in patients with NVAF: history of AF≥5 years [odds ratio (OR)=2.75, 95% confidence interval (CI) 1.98-3.82, P<0.01], lipoprotein(a)>300 g/L (OR=2.07, 95%CI 1.50-2.84, P<0.01), apolipoprotein (Apo)B>1.2 g/L (OR=1.91, 95%CI 1.25-2.93, P=0.003), left ventricular ejection fraction (LVEF) of 30%-49% (OR=2.45, 95%CI 1.63-3.69, P<0.01), left atrial diameter>40 mm (OR=1.54, 95%CI 1.16-2.07, P=0.003), and CHA2DS2-VASc score≥3 (OR=15.14, 95%CI 2.05-112.13, P=0.01). ApoAI>1.6 g/L was negatively correlated with the occurrence of SE (OR=0.28, 95%CI 0.15-0.51, P<0.01). Conclusions: History of AF≥5 years, lipoprotein(a)>300 g/L, elevated ApoB, left atrial diameter>40 mm, LVEF of 30%-49%, and CHA2DS2-VASC score≥3 are independent risk factors for SE whereas ApoAI>1.6 g/L is a protective factor against SE in patients with NVAF.

Identification of novel Mendelian disorders of the epigenetic machinery (MDEMs)-associated functional mutations and neurodevelopmental disorders.

BACKGROUND: Mendelian disorders of the epigenetic machinery (MDEMs) are a newly identified group of neurodevelopmental disorders (NDDs) and multiple congenital anomalies caused by mutations in genes encoding components of the epigenetic machinery. Many studies have shown that MDEM-associated mutations may disrupt the balance of chromatin states and trigger dysplasia. AIM: To help eight Chinese families with NDDs acquire a definitive diagnosis. METHODS: In this study, we used whole-exome sequencing to diagnose eight unrelated Chinese families with NDDs. We also verified the potential pathogenic variants by Sanger sequencing and analyzed the changes in gene expression along with histone methylation modifications. RESULTS: Eight variants of six epigenetic machinery genes were identified, six of which were novel. Six variants were pathogenic (P) or likely pathogenic (LP), while two novel missense variants (c.5113T>C in CHD1 and c.10444C>T in KMT2D) were classified to be variants of uncertain significance (VUS). Further functional studies verified that c.5113T>C in CHD1 results in decreased protein levels and increased chromatin modifications (H3K27me3). In addition, c.10444C>T in KMT2D led to a significant decrease in mRNA transcription and chromatin modifications (H3K4me1). Based on experimental evidence, these two VUS variants could be classified as LP. CONCLUSION: This study provided a definitive diagnosis of eight families with NDDs and expanded the mutation spectrum of MDEMs, enriching the pathogenesis study of variants in epigenetic machinery genes.

Unique motif shared by HLA-B*59:01 and HLA-B*55:02 is associated with methazolamide-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Han Chinese.

BACKGROUND: Methazolamide (MTZ) has been occasionally linked to the lethal Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which are associated with HLA-B*59:01. However, some MTZ-induced SJS/TEN (MTZ-SJS/TEN) cases are negative for HLA-B*59:01, implying that other genetic factors besides HLA-B*59:01 are contributing to MTZ-SJS/TEN. OBJECTIVES: To comprehensively identify HLA and non-HLA genetic susceptibility to MTZ-SJS/TEN in Han Chinese. METHODS: Eighteen patients with MTZ-SJS/TEN, 806 subjects of the population control and 74 MTZ-tolerant individuals were enrolled in this study. Both exome-wide and HLA-based association studies were conducted. Molecular docking analysis was employed to simulate the interactions between MTZ and risk HLA proteins. RESULTS: We found a strong signal in the major histocompatibility complex region on chromosome 6 with 22 SNPs reaching exome-wide significance. Compared with MTZ-tolerant controls, a significant association of HLA-B*59:01 with MTZ-SJS/TEN was validated [odds ratio (OR) = 146.00, 95% confidence interval (CI): 16.12-1321.98; P = 6.19 × 10-10 ]. Moreover, 66.7% of MTZ-SJS/TEN patients negative for HLA-B*59:01 were carriers of HLA-B*55:02, whilst 2.7% of the tolerant individuals were observed with HLA-B*55:02 (OR = 71.00, 95% CI: 7.84-643.10; P = 1.43 × 10-4 ). Within HLA-B protein, the E45-L116 motif could completely explain the association of HLA-B*59:01 and HLA-B*55:02 with MTZ-SJS/TEN (OR = 119.33, 95% CI: 29.19-1227.96; P = 4.36 × 10-13 ). Molecular docking analysis indicated that MTZ binds more stably to the pocket of HLA-B*59:01 and HLA-B*55:02 than to that of non-risk alleles of HLA-B*40:01 and HLA-C*01:02. CONCLUSIONS: This study confirmed the association of HLA-B*59:01 with MTZ-SJS/TEN and identified HLA-B*55:02 as a novel risk allele in Han Chinese with the largest sample size to date. Notably, the rs41562914(A)-rs12697944(A) haplotype, encoding E45-L116, is capable of serving as a powerful genetic predictor for MTZ-SJS/TEN with a sensitivity of 89% and specificity of 96%.

[Effect of RBP2 gene silencing on proliferation, migration and invasion of ovarian epithelial cancer SKOV3/DDP cells and its mechanism].

Objective: To explore the effect of down-regulation of retinol binding protein 2 (RBP2) expression on the biological characteristics of ovarian cancer cells and its mechanism. Methods: Knockdown of RBP2 and cisplatin (DDP)-resistant ovarian cancer cell line SKOV3/DDP-RBP2i was established, the negative control group and blank control group were also set. Cell counting kit 8 (CCK-8) was used to detect the cell proliferation ability, flow cytometry was used to detect cell apoptosis, scratch test and Transwell invasion test were used to detect cell migration and invasion ability, real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) and western blot were used to detect the expressions of molecular markers related to epithelial-mesenchymal transition (EMT). The effect of RBP2 on the growth of ovarian cancer was verified through experiment of transplanted tumors in nude mice, and the relationships between RBP2 expression and tumor metastasis and patient prognosis were analyzed using the clinical data of ovarian cancer in TCGA database. Results: After down-regulating the expression of RBP2, the proliferation ability of SKOV3/DDP cell was significantly reduced. On the fifth day, the proliferation activities of SKOV3/DDP-RBP2i group, negative control group and blank control group were (56.67±4.16)%, (84.67±3.51) and (87.00±4.00)% respectively, with statistically significant difference (P<0.001). The apoptosis rate of SKOV3/DDP-RBP2i group was (14.19±1.50)%, higher than (8.77±0.75)% of the negative control group and (7.48±0.52)% of the blank control group (P<0.001). The number of invasive cells of SKOV3/DDP-RBP2i group was (55.20±2.39), lower than (82.60±5.18) and (80.80±7.26) of the negative control group and the blank control group, respectively (P<0.001). The scratch healing rate of SKOV3/DDP-RBP2i group was (28.47±2.72)%, lower than (50.58±4.06)% and (48.92±4.63)% of the negative control group and the blank control group, respectively (P<0.001). The mRNA and protein expressions of E-cadherin in the SKOV3/DDP-RBP2i group were higher than those in the negative control group (P=0.015, P<0.001) and the blank control group (P=0.006, P<0.001). The mRNA and protein expression of N-cadherin in SKOV3/DDP-RBP2i group were lower than those in the negative control group (P=0.012, P<0.001) and the blank control group (P=0.005, P<0.001). The mRNA and protein expressions of vimentin in SKOV3/DDP-RBP2i group were also lower than those in the negative control group (P=0.016, P=0.001) and the blank control group (P=0.011, P=0.001). Five weeks after the cells inoculated into the nude mice, the tumor volume of SKOV3/DDP-RBP2i group, negative control group and blank control group were statistically significant different. The tumor volume of SKOV3/DDP-RBP2i group was smaller than those of negative control group and blank control group (P=0.001). Bioinformatics analysis showed that the expression of RBP2 in patients with metastatic ovarian cancer was higher than that without metastasis (P=0.043), and the median overall survival of ovarian cancer patients with high RBP2 expression was 41 months, shorter than 69 months of low RBP2 expression patients (P<0.001). Conclusion: Downregulation of the expression of RBP2 in SKOV3/DDP cells can inhibit cell migration and invasion, and the mechanism may be related to the inhibition of EMT.

Evaluation of the frequency of mutation genes in multidrug-resistant tuberculosis (MDR-TB) strains in Beijing, China.

The aim of this study was to explore the frequency and distribution of gene mutations that are related to isoniazid (INH) and rifampin (RIF)-resistance in the strains of the multidrug-resistant tuberculosis (MDR-TB) Mycobacterium tuberculosis (M.tb) in Beijing, China. In this retrospective study, the genotypes of 173 MDR-TB strains were analysed by spoligotyping. The katG, inhA genes and the promoter region of inhA, in which genetic mutations confer INH resistance; and the rpoB gene, in which genetic mutations confer RIF resistance, were sequenced. The percentage of resistance-associated nucleotide alterations among the strains of different genotypes was also analysed. In total, 90.8% (157/173) of the MDR strains belonged to the Beijing genotype. Population characteristics were not significantly different among the strains of different genotypes. In total, 50.3% (87/173) strains had mutations at codon S315T of katG; 16.8% (29/173) of strains had mutations in the inhA promoter region; of them, 5.5% (15/173) had point mutations at -15 base (C→T) of the inhA promoter region. In total, 86.7% (150/173) strains had mutations at rpoB gene; of them, 40% (69/173) strains had mutations at codon S531L of rpoB. The frequency of mutations was not significantly higher in Beijing genotypic MDR strains than in non-Beijing genotypes. Beijing genotypic MDR-TB strains were spreading in Beijing and present a major challenge to TB control in this region. A high prevalence of katG Ser315Thr, inhA promoter region (-15C→T) and rpoB (S531L) mutations was observed. Molecular diagnostics based on gene mutations was a useful method for rapid detection of MDR-TB in Beijing, China.

Diversification of reprogramming trajectories revealed by parallel single-cell transcriptome and chromatin accessibility sequencing.

Cellular reprogramming suffers from low efficiency especially for the human cells. To deconstruct the heterogeneity and unravel the mechanisms for successful reprogramming, we adopted single-cell RNA sequencing (scRNA-Seq) and single-cell assay for transposase-accessible chromatin (scATAC-Seq) to profile reprogramming cells across various time points. Our analysis revealed that reprogramming cells proceed in an asynchronous trajectory and diversify into heterogeneous subpopulations. We identified fluorescent probes and surface markers to enrich for the early reprogrammed human cells. Furthermore, combinatory usage of the surface markers enabled the fine segregation of the early-intermediate cells with diverse reprogramming propensities. scATAC-Seq analysis further uncovered the genomic partitions and transcription factors responsible for the regulatory phasing of reprogramming process. Binary choice between a FOSL1 and a TEAD4-centric regulatory network determines the outcome of a successful reprogramming. Together, our study illuminates the multitude of diverse routes transversed by individual reprogramming cells and presents an integrative roadmap for identifying the mechanistic part list of the reprogramming machinery.

TRIM59 attenuates inflammation and apoptosis caused by myocardial ischemia reperfusion injury by activating the PI3K/Akt signaling pathway.

The article "TRIM59 attenuates inflammation and apoptosis caused by myocardial ischemia reperfusion injury by activating the PI3K/Akt signaling pathway, Z.-Q. Lv, C.-Y. Yang, Q.-S. Xing, published in Eur Rev Med Pharmacol Sci 2020; 24(7): 4005-4015. DOI: 10.26355/eurrev_202004_20870. PMID: 32329876" has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause.

TRIM59 attenuates inflammation and apoptosis caused by myocardial ischemia reperfusion injury by activating the PI3K/Akt signaling pathway.

OBJECTIVE: Myocardial ischemia reperfusion injury (MIRI) is a common factor in heart-related diseases. The aim of this study was to explore the effect of TRIM59 gene on MIRI and its mechanism. MATERIALS AND METHODS: Rats were used to construct MIRI models, and TRIM59 gene was overexpressed in myocardium by Entranster technique to detect the effects of TRIM59 on myocardial oxidative stress, myocardial injury, and ATPase. In addition, rat myocardial H9c2 cells were cultured, and a hypoxia-reoxygenation model of H9c2 cells was constructed to detect the effect of TRIM59 overexpression on the inflammation and apoptosis of H9c2 cells. Finally, the PI3K/Akt signaling pathway inhibitor LY294002 was used to study the effect of TRIM59 on the PI3K/Akt signaling pathway. RESULTS: Overexpression of TRIM59 in vivo effectively reduced the expressions of MDA, CK, and LDH, and increased the expression of SOD and the activity of Na+-K+-ATPase and Ca2+-Mg2+-ATPase. In addition, overexpression of TRIM59 in H9c2 cells significantly reduced the expression of inflammatory cytokines (IL-1ß, IL-6, and TNF-α) and oxidative stress (ROS) levels. TRIM59 also significantly increased the activity of PI3K/Akt signaling pathway and promoted the phosphorylation of Akt. CONCLUSIONS: TRIM59 reduces the level of inflammation and apoptosis of myocardial cells caused by MIRI by activating the PI3K/Akt signaling pathway, thereby reducing myocardial injury.

[Study on the prevalence of Beijing genotype Mycobacterium tuberculosis and its relationship with second-line anti-tuberculosis drug resistance].

Objective: To explore the prevalence risk factors of Beijing genotype Mycobacterium tuberculosis (MTB) in Beijing and its correlation with second-line anti tuberculosis drug resistance. Methods: A total of 1 140 clinical MTB positive strains were collected from various districts in Beijing, and the drug sensitivity was detected by proportion method. Beijing genotype and non Beijing genotype MTB were identified by the method of Spoligotyping. Using SPSS 22.0 statistical software, chi square test or Fisher exact probability test was used to analyze the experimental data. Results: Among 1 140 MTB clinical isolates, 941 (82.5%) were Beijing genotype MTB, 199 were non Beijing genotype MTB. There were 663 males (70.5%) in Beijing genotype and 124 males (62.3%) in non Beijing genotype strains. There were significant differences in the proportion of males between the two genotypes [P=0.021, OR (95% CI):1.442 (1.048-1.985)]. There were 441 floating population (46.9%) in Beijing genotype MTB and 78 floating population (39.2%) in non Beijing genotype MTB. There was a significant difference in the proportion of floating population between the two genotypes [P=0.048,OR (95%CI):1.368(1.001-1.869)]. There were 129 patients (13.7%) aged 65 or older in Beijing genotype MTB, 40 patients (20.1%) aged 65 or older in non Beijing genotype MTB. The difference was statistically significant [P=0.021, or (95% CI): 0.631 (0.426-0.936)]. The resistance drug rates of Levofloxacin (Lfx), Amikacin (Am), Capreomycin (Cm), Para-aminosalicylic (PAS) in Beijing genotypes were 5.5% (52/941), 1.3% (12/941), 3.2% (30/941) and 3.0% (28/941), respectively, and those of non Beijing genotypes were 10.6% (21/199), 8.5% (17/199, 12.6% (25/199) and 11.6% (23/199), the difference was statistically significant (all P<0.05). There were 58 (6.2%) multidrug-resistant (MDR) strains in Beijing genotype MTB and 19 (9.5%) multidrug-resistant strains in non Beijing genotype. There was no significant difference in the proportion of MDR strains between Beijing genotype and non Beijing genotype (P>0.05). Conclusions: Beijing genotype MTB is widespread in Beijing and has a higher proportion in male population and floating population. Compared with non Beijing genotype, Beijing genotype MTB has a lower resistance rate to Lfx, Am, Cm and PAS, and there is no significant difference in the proportion of MDR-TB patients between the two genotypes.

[Application of arterial duct stent in ductus-dependent hypoplastic right heart syndrome].

Objective: To summarize the experience of arterial duct (AD) stenting in children with ductus-dependent hypoplastic right heart syndrome (HRHS). Methods: Seven children including 4 cases of pulmonary atresia with intact ventricular septum (PA-IVS) with HRHS and 3 cases of critical pulmonary stenosis (CPS)-IVS with HRHS underwent AD stenting in Qingdao Women and Children's Hospital between January 2012 and January 2019. During the same period, 9 patients of PA-IVS with HRHS received Blalock Taussig (B-T) shunt. Two groups of children on the operation time, hospital stay time, intensive care time and mortality were compared.T test or Mann-Whitney U test was used for comparison between the two groups. Results: There was no significant difference in the age (18 (7-100) vs. 17 (1-142) d, U=31.000, P>0.05) and weight ((3.8±1.1) vs. (3.7±1.3) kg, t=0.272, P>0.05) between the AD stenting group and the B-T group.The operation time ((108±7) vs. (160±49) min, t=-4.304), intensive care time ((3.4±1.0) vs. (6.3±4.5) d, t=-8.692) and total hospitalization time ((10.3±1.0) vs. (26.3±1.0) d, t=-7.822) in the AD stenting group were differed significantly compared with the B-T group (all P<0.05). The transcutaneous oxygen saturation improved significantly (0.723±0.125 vs. 0.926±0.005, t=-6.044, P<0.05) after AD stenting. The diameter of AD stent ranged from 3.5 to 4.0 mm, and the length of AD stent was 16-21 mm. There were no complications such as vascular injury, acute thrombus, catheter spasm and death in the AD stenting group. The mortality of children in the B-T group was 3 in 9 cases. Three cases in the AD stenting group received pulmonary valvulotomy and bilateral Glenn operation at 6, 9 and 9 months after AD stenting, respectively. Conclusions: AD stenting is a feasible, effective, safe and minimally invasive procedure for children with ductus-dependent HRHS. It can even be used as an alternative to B-T shunt.

MicroRNA-193a-3p participates in the progression of rheumatoid arthritis by regulating proliferation and apoptosis of MH7A cells through targeting IGFBP5.

OBJECTIVE: This study aims to explore the regulatory effect of microRNA-193a-3p on rheumatoid arthritis (RA) and its underlying mechanism. PATIENTS AND METHODS: Expression level of microRNA-193a-3p in synovial tissues extracted from 30 RA patients and healthy controls was detected by quantitative Real-time polymerase chain reaction (qRT-PCR). MH7A cells were subjected to TNF-α induction for constructing the in vitro RA model. After transfection of microRNA-193a-3p inhibitor in MH7A cells, proliferation and apoptosis were detected by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. Enzyme-linked immunosorbent assay (ELISA) was conducted to determine levels of interleukin 6 (IL-6) and IL-8 in MH7A cells. Subsequently, the dual-luciferase reporter gene assay was carried out to verify the binding condition between microRNA-193a-3p and IGFBP5. Rescue experiments were conducted to evaluate the proliferation and apoptosis of MH7A cells with knockdown of microRNA-193a-3p and IGFBP5. RESULTS: MicroRNA-193a-3p was highly expressed in synovial tissues of RA patients and TNF-α-induced MH7A cells than those of controls. TNF-α induction significantly increased the proliferative rate of MH7A cells, reaching the peak at 96 h. After knockdown of microRNA-193a-3p, the promoted proliferation by TNF-α induction was significantly inhibited. In addition, TNF-α induction significantly inhibited the apoptosis of MH7A cells. After inhibition of microRNA-193a-3p expression, the inhibited apoptosis by TNF-α induction remarkably increased. TNF-α induction upregulated levels of IL-6 and IL-8 in MH7A cells, which were remarkably reduced after the microRNA-193a-3p knockdown. Dual-luciferase reporter gene assay confirmed that IGFBP5 could bind to microRNA-193a-3p, and its expression was negatively regulated by microRNA-193a-3p. The regulatory effects of microRNA-193a-3p on proliferation and apoptosis of MH7A cells were reversed by IGFBP5 knockdown. CONCLUSIONS: MicroRNA-193a-3p is highly expressed in the synovial tissues and cells of rheumatoid arthritis. MicroRNA-193a-3p participates in the process of rheumatoid arthritis by regulating the proliferation, apoptosis and inflammatory response of MH7A cells through targeting IGFBP5.

Radio frequency measurement and tuning of a 13 MeV Alvarez-type drift tube linac for a compact pulsed hadron source.

This paper describes the radio frequency (RF) measurement and tuning result of a 13 MeV Alvarez-type drift tube linac (DTL) for a compact pulsed hadron source (CPHS) at Tsinghua University. The design, machining, assembly, and alignment of the DTL are presented for integrity. The CPHS project consists of a high-current proton linac (13 MeV, 16 kW, peak current of 50 mA, 0.5 ms pulse width at 50 Hz), a neutron target station, a small-angle neutron scattering instrument, and a neutron imaging/radiology station. The linac contains an electron cyclotron resonance ion source, a low energy beam transport line, a four-vane radio frequency quadrupole (RFQ) accelerator, an Alvarez-type DTL, a high energy beam transport line, and a RF power supply and distributor. Construction on the CPHS started in June 2009, and the CPHS has provided 2000 h since 2013 to users with the neutrons produced by the 3 MeV proton beam from the radio frequency quadrupole bombarding on the beryllium target as an achievement of its mid-term objective. Presently, the tuning of the assembled DTL cavity has been completed successfully. The 4.3-m-long DTL consists of 40 accelerating cells, among which 39 full-length drift tubes (DTs) are suspended inside the cavity, and two half-length DTs are mounted inside the two end flanges of the cavity. Each DT contains a permanent magnet quadrupole. Thirteen post couplers and nine tuners are available for the tuning of the field. The relative error of the field after tuning is within ±1.6%, with a tilt sensitivity within ±33%/MHz in all cells. The beam energy will reach its designed value of 13 MeV after the DTL is installed in the beam line downstream the 3 MeV RFQ accelerator.

[Analysis of the KCNQ1 gene mutation in 2 families with congenital long QT syndrome type 1 in Xinjiang Uygur Autonomous Region].

Objective: Present study analyzed the association betwen the postassium voltage-gated channel KQT-like subfamily member 1 gene (KCNQ1) mutation and the clinical and the electrocardiographic features in 2 pedigrees with congenital long QT syndrome type 1 (LQT1) in Xinjiang Uygur Autonomous Region. Methods: Three family members were diagnosed as LQT1 patients in 2 Uygur congenital LQT1 families, these 3 LQT1 patients served as long QT group, 24 Uygur healthy volunteers served as control group. Electrocardiogram (ECG) and the gene detection were applied to compare the ECG and molecular genetic features between the long QT group and control group, and to explore the relationship between the KCNQ1 gene mutation and the clinical and the electrocardiographic features in these 2 families with congenital long QT syndrome type 1. Results: The LQT1 was diagnosed in 3 cases of the 2 pedigrees. The common features of ECG were QTc>480 ms, prolonged ST segment, and delayed T wave. The gene test evidenced a polymorphism of KCNQ1 gene exon 13:47G➝A(R16R). The mutation of 133G➝A9(G45S) of exon 16 resulted in the change of the original glycine (G) to serine (s). The ECG of the control group were normal, and there were no KCNQ1 gene mutations in control group. Conclusion: The exon sequencing results of KCNQ1 gene in 2 Xinjiang Uygur congenital long LQT1 families showed that exon16 missense changes (133G to A (G45S)) can lead to amino acid mutation, this mutation may be a pathogenic mutation. Subsequent validation of the expanded sample will provide a reference for revealing the relationship between the KCNQ1 gene and the pathogenesis of LQT1.

Comparative efficacy and safety of contact force-sensing catheter and second-generation cryoballoon ablation for atrial fibrillation: a meta-analysis.

This meta-analysis compared the efficacy and safety of the contact force (CF)-sensing catheter and second-generation cryoballoon (CB) ablation for treating atrial fibrillation (AF). Six controlled clinical trials comparing ablation for AF using a CF-sensing catheter or second-generation CB were identified from PubMed, EMBASE, Cochrane Library, Wanfang Data, and China National Knowledge Infrastructure. The procedure duration was significantly lower in the CB group compared with that in the CF group [mean difference (MD)=29.4; 95%CI=17.84-40.96; P=0.01], whereas there was no difference between the groups for fluoroscopy duration (MD=0.59; 95%CI=-4.48-5.66; P=0.82). Moreover, there was no difference in the incidence of non-lethal complications (embolic event, tamponade, femoral/subclavian hematoma, arteriovenous fistula, pulmonary vein stenosis, phrenic nerve palsy, and esophageal injury) between the CB and the CF groups (8.38 vs 5.35%; RR=0.66; 95%CI=0.37-1.17; P=0.15). Transient phrenic nerve palsy occurred in 17 of 326 patients (5.2%) of the CB group vs none in the CF group (RR=0.12; 95%CI=0.03-0.43; P=0.001). A comparable proportion of patients in CF and CB groups suffered from AF recurrence during the 12-month follow-up after a single ablation procedure [risk ratio (RR)=1.03; 95%CI=0.78-1.35; P=0.84]. AF ablation using CF-sensing catheters and second-generation CB showed comparable fluoroscopy duration and efficacy (during a 12-month follow-up), with shorter procedure duration and different complications in the CB group.