Evaluation of metoprolol standard dosing pathway in Chinese patients with acute coronary syndrome: a prospective multicenter single-arm interventional study.

OBJECTIVE: To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS). METHODS: In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4. RESULTS: Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group. CONCLUSIONS: In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.

The P300 Auditory Event-Related Potential May Predict Segregation of Competing Speech by Bimodal Cochlear Implant Listeners.

Compared to normal-hearing (NH) listeners, cochlear implant (CI) listeners have greater difficulty segregating competing speech. Neurophysiological studies have largely investigated the neural foundations for CI listeners' speech recognition in quiet, mainly using the P300 component of event-related potentials (ERPs). P300 is closely related to cognitive processes involving auditory discrimination, selective attention, and working memory. Different from speech perception in quiet, little is known about the neurophysiological foundations for segregation of competing speech by CI listeners. In this study, ERPs were measured for a 1 vs. 2 kHz contrast in 11 Mandarin-speaking bimodal CI listeners and 11 NH listeners. Speech reception thresholds (SRTs) for a male target talker were measured in steady noise or with a male or female masker. Results showed that P300 amplitudes were significantly larger and latencies were significantly shorter for the NH than for the CI group. Similarly, SRTs were significantly better for the NH than for the CI group. Across all participants, P300 amplitude was significantly correlated with SRTs in steady noise (r = -0.65, p = 0.001) and with the competing male (r = -0.62, p = 0.002) and female maskers (r = -0.60, p = 0.003). Within the CI group, there was a significant correlation between P300 amplitude and SRTs with the male masker (r = -0.78, p = 0.005), which produced the most informational masking. The results suggest that P300 amplitude may be a clinically useful neural correlate of central auditory processing capabilities (e.g., susceptibility to informational masking) in bimodal CI patients.

Effect of neuregulin-1 on the auditory cortex in adult C57BL/6J mice.

OBJECTIVES: We sought to explore whether neuregulin-1(NRG1) would have a protective effect on the auditory cortices of adult C57BL/6J mice. MATERIALS AND METHODS: We used RTPCR and Western blot (WB) to detect the expression of NRG1 and ERBB4 (the receptor of NRG1) in the auditory cortices of C57BL/6J mice of different ages (6-8 weeks and 42-44 weeks). Three groups of 42-44 week-old C57BL/6J mice were intraperitoneally injected with mouse neurotrophic factor (m-NGF), NRG1, or saline for two months. We observed the ultrastructures of the auditory cortices of adult mice after treatment using transmission electron microscopy. Additionally, we observed expression of NRG1 in the auditory cortices by immunohistochemistry. RESULTS: Expression of NRG1 and ERBB4 in the auditory cortices of C57BL/6J mice at the age of 42-44 weeks was lower compared with 6-8 week-old mice. The ultra-structures of the auditory cortices, including the neurons and myelin sheaths, as revealed by transmission electron microscopy were healthier in the m-NGF and NRG1 treatment groups than those in the saline group. We found that expression of NRG1 in the auditory cortices after treatment in the m-NGF and NRG1 groups, especially in the NRG1 group, was higher than that in the saline group. CONCLUSION: We concluded that with increasing age, NRG1 in the auditory cortices of C57BL/6J mice gradually decreased, and that NRG1 had a protective effect on the auditory cortices in adult C57BL/J mice.

The association between CDH1 promoter methylation and patients with ovarian cancer: a systematic meta-analysis.

BACKGROUND: The down-regulation of E-cadherin gene (CDH1) expression has been regarded as an important event in cancer invasion and metastasis. However, the association between CDH1 promoter methylation and ovarian cancer remains unclear. A meta-analysis was conducted to evaluate the potential role of CDH1 promoter methylation in ovarian cancer. METHODS: Relevant articles were identified by searches of PubMed, EMBASE, Cochrane Library, CNKI and Wanfang databases. The pooled odds ratio (OR) and corresponding 95 % confidence interval (CI) were calculated to assess the strength of association. RESULTS: Nine studies were performed using the fixed-effects model in this study, including 485 cancer tissues and 255 nonmalignant tissues. The findings showed that CDH1 promoter methylation had an increased risk of ovarian cancer in cancer tissues (OR = 8.71, P < 0.001) in comparison with nonmalignant tissues. Subgroup analysis of the ethnicity showed that the OR value of CDH1 methylation in Asian population subgroup (OR = 13.20, P < 0.001) was higher than that in Caucasian population subgroup (OR = 3.84, P = 0.005). No significant association was found between ovarian cancer and low malignant potential (LMP) tumor (P = 0.096) among 2 studies, and between CDH1 promoter methylation and tumor stage and tumor histology (all P > 0.05). There was not any evidence of publication bias by Egger's test (all P > 0.05). CONCLUSIONS: CDH1 promoter methylation can be a potential biomarker in ovarian cancer risk prediction, especially Asians can be more susceptible to CDH1 methylation. However, more studies are still done in the future.

Targeted next-generation sequencing of candidate genes reveals novel mutations in patients with dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is a major cause of sudden cardiac death and heart failure, and it is characterized by genetic and clinical heterogeneity, even for some patients with a very poor clinical prognosis; in the majority of cases, DCM necessitates a heart transplant. Genetic mutations have long been considered to be associated with this disease. At present, mutations in over 50 genes related to DCM have been documented. This study was carried out to elucidate the characteristics of gene mutations in patients with DCM. The candidate genes that may cause DCM include MYBPC3, MYH6, MYH7, LMNA, TNNT2, TNNI3, MYPN, MYL3, TPM1, SCN5A, DES, ACTC1 and RBM20. Using next-generation sequencing (NGS) and subsequent mutation confirmation with traditional capillary Sanger sequencing analysis, possible causative non-synonymous mutations were identified in ~57% (12/21) of patients with DCM. As a result, 7 novel mutations (MYPN, p.E630K; TNNT2, p.G180A; MYH6, p.R1047C; TNNC1, p.D3V; DES, p.R386H; MYBPC3, p.C1124F; and MYL3, p.D126G), 3 variants of uncertain significance (RBM20, p.R1182H; MYH6, p.T1253M; and VCL, p.M209L), and 2 known mutations (MYH7, p.A26V and MYBPC3, p.R160W) were revealed to be associated with DCM. The mutations were most frequently found in the sarcomere (MYH6, MYBPC3, MYH7, TNNC1, TNNT2 and MYL3) and cytoskeletal (MYPN, DES and VCL) genes. As genetic testing is a useful tool in the clinical management of disease, testing for pathogenic mutations is beneficial to the treatment of patients with DCM and may assist in predicting disease risk for their family members before the onset of symptoms.

Targeted Next-Generation Sequencing Reveals Hot Spots and Doubly Heterozygous Mutations in Chinese Patients with Familial Cardiomyopathy.

As a common cardiac disease mainly caused by gene mutations in sarcomeric cytoskeletal, calcium-handling, nuclear envelope, desmosomal, and transcription factor genes, inherited cardiomyopathy is becoming one of the major etiological factors of sudden cardiac death (SCD) and heart failure (HF). This disease is characterized by remarkable genetic heterogeneity, which makes it difficult to screen for pathogenic mutations using Sanger sequencing. In the present study, three probands, one with familial hypertrophic cardiomyopathy (FHCM) and two with familial dilated cardiomyopathy (FDCM), were recruited together with their respective family members. Using next-generation sequencing technology (NGS), 24 genes frequently known to be related to inherited cardiomyopathy were screened. Two hot spots (TNNI3-p.Arg145Gly, and LMNA-p.Arg190Trp) and double (LMNA-p.Arg190Trp plus MYH7-p.Arg1045His) heterozygous mutations were found to be highly correlated with familial cardiomyopathy. FDCM patients with doubly heterozygous mutations show a notably severe phenotype as we could confirm in our study; this indicates that the double mutations had a dose effect. In addition, it is proposed that genetic testing using NGS technology can be used as a cost-effective screening tool and help guide the treatment of patients with familial cardiomyopathy particularly regarding the risk of family members who are clinically asymptomatic.