Gender- and age-related differences in distinct phenotypes of hypertrophic cardiomyopathy-associated mutation MYBPC3-E334K.

The mutation MYBPC3-E334K is a culprit mutation of hypertrophic cardiomyopathy (HCM). The pathogenicity of MYBPC3-E334K is conflicting in ClinVar because of the limited segregation data and the relatively high frequency in gnomAD (0.03% overall, with 0.3% in East Asians and 0.8% in Japanese). The main aim is to clarify the clinical importance and phenotype-genotype correlations in subjects with or without MYBPC3-E334K alone. The prevalence of MYBPC3-E334K was sequenced in 1017 HCM unrelated probands. The clinical features, morphology phenotypes, and electrical phenotypes were further analyzed according to the phenotype and genotype status in families with single-mutation MYBPC3-E334K. Nine of 1017 (0.88%) unrelated HCM probands were detected harboring MYBPC3-E334K, and three of them harbored a second variant in sarcomere protein gene. Family study and co-segregation analyses indicated that patients with single-mutation MYBPC3-E334K showed autosomal dominant mode of inheritance with incomplete penetrance. The overall disease penetrance was 52.6%, and the disease penetrance was higher in males than in females (100% in men vs 25% in women, p = 0.003). The mean age at diagnosis of males was approximately 25 years younger than females (36.57 ± 18.65 vs 62.33 ± 12.10, p = 0.062). The variant MYBPC3-E334K was classified as a likely pathogenic variant, and a second sarcomere variant did not reveal obvious cumulative effects. The patients harboring single-mutation MYBPC3-E334K had incomplete penetrance, and males demonstrated higher penetrance and early onset HCM than females. A second sarcomere variant did not reveal obvious cumulative effects.

Clinical and molecular characterization of seven patients with Danon disease.

Danon disease is an X-linked glycogen storage disease characterized by skeletal myopathy, cardiomyopathy and intellectual impairment. It is caused by a loss-of-function mutation in the lysosome-associated membrane protein-2 (LAMP2) gene. In the present study, exon and boarding intron analysis of 96 cardio disease-associated genes was performed in 770 patients with hypertrophic cardiomyopathy (HCM) using second-generation sequencing. Next, the identified mutations were confirmed in family members of the patients and 300 healthy controls. Detailed clinical, electrocardiographic (ECG) and echocardiographic findings were recorded. A pathogenic mutation in LAMP2 was identified in 7 patients who phenotypically presented with HCM. A total of four patients had a fragmented QRS complex (fQRS) on surface ECG. In addition, two patients presented with ventricular preexcitation with a short PR interval. Compared with the patients with protein kinase AMP-activated non-catalytic subunit γ2 syndrome and Fabry disease, the 7 patients with Danon disease presented at an earlier age, had a smaller left atrial size, a thinner maximal left ventricular wall thickness and a lower probability of pacemaker implantation. Compared with 12 sex- and age-matched patients with sarcomere-protein mutations, the 4 patients with Danon disease had a lower left ventricular outflow tract gradient and worse diastolic function. The present study provided a comprehensive comparison of different pathologies presenting with HCM and reported on features of early-onset Danon disease, including the characteristic preexcitation and fQRS on ECG. This may provide valuable information that may be utilized for the early diagnosis and treatment of patients with Danon disease. The present study was registered as a clinical trial with ClinicalTrials.gov (Sep. 2, 2016; registry no. NCT02888132).

Metabolomic and transcriptomic profiling of three types of litchi pericarps reveals that changes in the hormone balance constitute the molecular basis of the fruit cracking susceptibility of Litchi chinensis cv. Baitangying.

Many Litchi chinensis cv. Baitangying orchards are suffering from a serious fruit cracking problem, but few studies have improved our understanding of the mechanism or the molecular basis of cracking susceptibility in 'Baitangying'. We conducted metabolome and transcriptome analyses of three types of litchi pericarps. To prevent passive progression after fruit cracking from affecting the results, we mainly focused on 11 metabolites and 101 genes that showed the same regulatory status and overlap in pairwise comparisons of cracking 'Baitangying' versus noncracking 'Baitangying' and noncracking 'Baitangying' versus noncracking 'Feizixiao'. Compared with the cracking-resistant cultivar 'Feizixiao', the 'Baitangying' pericarp has higher abscisic acid contents, and the presence of relevant metabolites and genes suggests increased biosynthesis of ethylene and jasmonic acid and decreased auxin and brassinosteroid biosynthesis. The fruit cracking-susceptible trait in 'Baitangying' might be associated with differences in the balance of these five types of hormones between the pericarp of this cultivar and that of 'Feizixiao'. Additionally, combined analyses showed a correspondence between the metabolite profiles and transcript patterns. qRT-PCR validation indicated the reliability of our high-throughput results. The acquired information might help in further studying the mechanisms that mediate fruit cracking susceptibility in 'Baitangying' and other litchi cultivars.

Coarctation of the Aorta with Aortic Arch Hypoplasia: Midterm Outcomes of Aortic Arch Reconstruction with Autologous Pulmonary Artery Patch.

BACKGROUND: Coarctation of the aorta (CoA) with aortic arch hypoplasia (AAH) is a relatively common congenital heart disease in clinical practice. Nonetheless, the corrective surgical technique for infants and children is a clinical problem that remains controversial. In this study, we sought to evaluate the surgical effects of aortic arch (AA) reconstruction with coarctation resection and aortoplasty with autologous pulmonary artery patch for infants and young children with CoA and AAH. METHODS: Between January 2009 and December 2015, a total of 22 infants and young children with CoA and AAH who underwent coarctation resection and aortoplasty with autologous pulmonary artery patch were enrolled in this study. The median age of patients was 4.5 (Q1, Q3: 2.0, 14.0) months and the median body weight was 5.75 (Q1, Q3: 4.10, 9.38) kg. All patients were diagnosed with CoA and AAH, and concomitant cardiac anomalies were corrected in one stage. Perioperative and postoperative data were collected and analyzed using the paired sample t-test. RESULTS: No perioperative deaths occurred. No residual obstruction was detected by echocardiography. The postoperative pressure difference across the repaired segment of CoA was 14.05 ± 4.26 mmHg (1 mmHg = 0.133 kPa), which was smaller than the preoperative pressure difference (48.30 ± 15.73 mmHg; t = -10.119, P < 0.001). The median follow-up time was 29.0 (Q1, Q3: 15.5, 57.3) months. There was no death during the follow-up period, and all patients experienced obvious clinical improvement. Only one child underwent subsequent aortic balloon angioplasty due to restenosis. Computed tomography angiography showed that the AA morphology was smooth, with no aortic aneurysm or angulation deformity. CONCLUSION: AA reconstruction with coarctation resection and aortoplasty with autologous pulmonary artery patch could effectively correct CoA with AAH, and the rate of reintervention for restenosis is low.

[Drug resistance and associated factors on HIV in Liangshan prefecture, Sichuan province].

OBJECTIVE: To investigate the HIV drug resistance among HIV/AIDS patients who had received highly active antiretroviral treatment (HAATR) in Liangshan prefecture and related factors. METHODS: This investigation was conducted from August to October 2010. Data on epidemiology, treatment, CD4(+) T cell, viral load and drug resistance tests were collected. RESULTS: 233 (73.50%) had a viral load of < 1000 copy/ml, with the median CD4(+) T cell count as 329 cell/µl. 26 samples appeared to be drug resistant, with the rate as 8.20%. Among 84 patients with antiviral therapy failure, the overall drug resistance rate was 30.95% (26/84). While 24 (28.57%) were resistant to non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs. Among nucleoside reverse transcriptase inhibitors (NRTI), 7 (8.33%) were resistant. 1 (1.19%) had protease inhibitor (PI) resistance mutations identified. Factors that significantly associated with drug resistance would include: being injecting drug users (AOR = 3.37, 95%CI: 1.06 - 10.66, P = 0.0390), having had chronic diarrhea > 1 month (AOR = 8.38, 95%CI: 1.87 - 37.69, P = 0.0055), having had CD4(+) T cell < 200 (AOR = 3.48, 95%CI: 1.29 - 9.39, P = 0.0139), being residents from Butuo area (AOR = 17.68, 95%CI: 4.97 - 62.86, P < 0.0001). When comparing with other areas, data from Butuo showed that people who carried Yi ethnicity (AOR = 17.35, 95%CI: 2.01 - 149.73, P = 0.0095) and were literate (having had primary or higher levels of education) (AOR = 0.18, 95%CI: 0.08 - 0.42, P < 0.0001), being married or having cohabited relations (AOR = 8.17, 95%CI: 2.35 - 28.39, P = 0.001) were found to be less adherent (AOR = 0.05, 95%CI: 0.02 - 0.13, P < 0.0001) to the treatment. CONCLUSION: Successful antiviral outcomes were seen among those AIDS patients under treatment, in Liangshan prefecture. Resistance rates were significantly different in regions. For IDUs, enforcement on subjects including prevention on drug resistance, adherence to HAART and treatment for drug addiction should be strengthened and programs being integrated.

[Determination of trace chrysene in environmental water by solid-phase microextraction coupled with high performance liquid chromatography].

A rapid method for the determination of trace chrysene in environmental water by solid-phase microextraction (SPME) coupled with high performmnce liquid chromatography (HPLC) was developed. The experimental conditions of SPME, such as extraction time, extraction temperature, effect of ion strength, desorption time, desorption solution, desorption mode and the analytical conditions of HPLC were optimized. The optimal conditions were room temperature, 1,100 r/min of stirring rate, 30 min of extraction time, 3 min of desorption time, and methanol as the desorption solution. Methanol was used as the mobile phase on a C18 reversed phase chromatographic column. The flow rate was 1 mL/min. The detection wavelength was 266 nm on a UV-Vis detector. The linear range was from 0.013 microgram/L to 3.0 micrograms/L, the detection limit was 2.7 ng/L, and the relative standard deviation (RSD) was 5.6%. The method was used for the determination of trace chrysene in tap water, mineral water, rain water and river water. The recoveries were from 103.2% to 119.3%, the RSDs were from 4.8% to 10.2%. The method is fast, convenient, sensitive, solvent-free, and suitable for the determination of trace chrysene in environmental water.