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Background: Methylmalonic aciduria (MMA) combined with homocystinuria, cobalamin(cbl)C deficiency type (OMIM 277400), is the most common autosomal recessive inherited disorder of intracellular cobalamin metabolism caused by mutations in the MMACHC gene (OMIM 609831), of which more than 100 mutations have been identified to date. In this study, we only identified a coding mutation in one allele at the MMACHC gene locus, and no large fragments deletion or duplication were found. Up to now, only three epimutation cblC cases were reported. We hypothesized whether the MMACHC was hypermethylated. Methods: To address this hypothesis, the entire coding region and adjacent splice sites of the panel genes involved in metabolic diseases were sequenced using the Illumina HiSeq X platform, followed by confirmation via Sanger sequencing in their parents and brothers. Methylation analysis of the MMACHC was performed using an EpiTect Bisulfite Kit and methylation‐specific PCR (MSP) to investigate the role of epimutations in cblC disease. Results: We identified a clearly pathogenic single heterozygous c.658_660del, p. (K220del) mutation, which was also identified in the mother. Analysis of the MMACHC indicated a heterozygous epimutation consisting of 34 hypermethylated CpG sites in a CpG island encompassing the promoter and first exon of the MMACHC, which was also identified in the father. Furthermore, we identified a single heterozygous c.*2C>T mutation in the sixth exon of the PRDX1 (OMIM 176763) in patients and their fathers, which was the only sequence variation that segregated with the MMACHC methylation. Neither c.658_660del and epimutation in MMACHC nor c.*2C>T in PRDX1 was discovered in her brother. Conclusion: We report compound heterozygotes in MMACHC for a genetic mutation and an epimutation in cblC cases. To our best knowledge, this is the first report of two cblC cases from China caused by compound heterozygous mutations with a coding mutation in one allele and an epimutation in the other at the MMACHC locus. [ABSTRACT FROM AUTHOR]

Purpose: Silent new ischemic cerebral lesions (sNICL) detected by diffusion-weighted imaging (DWI) are common after carotid artery stenting (CAS). As part of the Revascularization of Extracranial Carotid Artery Stenosis (RECAS) study, this work aimed to determine predictors of sNICL detected by DWI following CAS. Methods: A total of 694 patients eligible for the RECAS study treated in Xuanwu Hospital, Capital Medical University, with complete imaging data were included in this retrospective study. The patients were asymptomatic after CAS, and those with stroke, transient ischemic attack (TIA), or death were excluded. The RECAS protocol specified that DWI was completed 1–7 days before the procedure and within 3 days after CAS. Several parameters were assessed for associations with sNICL occurrence after CAS in univariate analysis. Finally, multivariate analysis was performed to determine risk factors for sNICL. Results: The rate of post-procedural sNICL in CAS was 51.3% (356/694 patients with sNICL). All patients underwent stenting with embolic protection devices. Univariate analysis showed that diabetes mellitus (P = 0.008), ipsilateral calcified plaques (P = 0.036), ipsilateral ulcerated plaques (P = 0.026), pre-dilatation (P = 0.003), and open-cell stent use (P < 0.001) were significantly associated with sNICL occurrence in CAS. Multivariate analysis revealed that diabetes mellitus (P = 0.006), ipsilateral calcified plaques (P = 0.024), ipsilateral ulcerated plaques (P = 0.021), and open-cell stent use (P < 0.001) were independent risk factors for sNICL. Conclusions: Patients with diabetes, calcified or ulcerated plaques who undergo CAS with open-cell stent application, are at high risk of sNICL. Large-scale prospective randomized controlled trials are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Background Breast cancer (BC) displays different clinicopathological features and outcomes based on patient age, molecular subtype, and treatment. However, such features in BC patients in northwest China are unclear. This study investigated the clinicopathological features and overall survival (OS) of early stage BC patients using a population-based study. Methods Patients who were newly diagnosed with BC at the First Affiliated Hospital of Xi'an Jiaotong University between January 2001 and June 2012 were included. Clinicopathological features and OS were assessed. Results The median age of 1287 patients was 50 years, with an average tumor size of 2.65 cm. Additionally, 42.7% were luminal A, 25.6% luminal B, 9.3% Her2 overexpression, and 17.7% triple negative. The cut-off age was 35 years, and young patients (< 35) tended to have larger tumors, ≥ 4 positive lymph nodes, grade 2 or 3 histology, non-luminal types, high Ki67, and poor outcomes. Patients with luminal A tumors showed moderate features: 50.6% had tumors < 2 cm, 56.7% had negative lymph nodes. Patients with Her2 overexpression tumors showed aggressive features and the poorest survival (5-year OS 67.6%). Patients with triple negative tumors were the youngest (average 48.4 years), but had the largest proportion of grade 3 histology and poor outcomes. Conclusion Our results are consistent with those in other provinces in China, but showed an earlier age at diagnosis and more aggressive pathological features compared to developed countries. Additionally, each molecular subtype showed specific features and different survival outcomes. [ABSTRACT FROM AUTHOR]

A phase-matched filtering technique is applied to extract fundamental mode signals from Rayleigh waves recorded at 62 digital seismic stations in the Yunnan and Sichuan regions. We use the fundamental mode of vibrations at two stations that are located on the same great circle as the focus to calculate an inter-station attenuation coefficient of the Rayleigh wave with periods between 0. 0 and 80.64 s, and invert for the inter-station S-wave Q-factor ( Q) at depths of 0-200 km. The results indicate that Q in Yunnan is 20-140, presenting a low Q background with apparent lateral variation. Taking the Honghe Fault as the boundary, Q of the crust is only 20 on the west side, extending to a depth of 120 km. The distribution of Q is consistent with large-scale Cenozoic volcanic and intrusive rocks in western Yunnan, implying that the crust and mantle are in the thermally active state. In the eastern Yunnan Block, east of the Xiaojiang Fault, Q in the upper 120 km is 140 in the south but only 20 in the north. Additionally, around the Dukou-Chuxiong in the mid-Yunnan Block, Q in the lithosphere is relatively high at 60-100, corresponding to a stiff crust. This is because the suture between the Indian and Eurasian plates reversed the tension in the rifting stage into the compression of orogenesis, leading to the closure of a gap in the crust. After some time, interstitial fluids gradually disappeared, resulting in a high velocity layer in the crust and low heat flow on the surface. The Yunnan region consists of an obvious block of elevated Q, distributed within the low background, consistent with the distribution of heat-flow values on the surface. The Honghe and Xiaojiang faults are tectonic boundaries in addition to being boundaries between regions of high and low crustal Q. The low Q is probably the result of crustal rupture and disturbance caused by strong earthquakes and the upwelling of hot substances along the deep fault zones. [ABSTRACT FROM AUTHOR]