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Background Light-chain (AL) amyloidosis is the most common type of systemic amyloidosis with poor prognosis. Currently, the predictors of cardiac involvement and prognostic staging systems are primarily based on conventional echocardiography and serological biomarkers. We used three-dimensional speckle tracking echocardiography (STE-3D) measurements of strain, hypothesizing that it could detect cardiac involvement and aid in prediction of mortality. Methods We retrospectively analysed 74 consecutive patients with biopsy-proven AL amyloidosis. Among them, 42 showed possible cardiac involvement and 32 without cardiac involvement. LV global longitudinal strain (GLS), global radial strain, global circumferential strain and global area strain (GAS) measurements were obtained. Results The GLS and GAS were considered significant predictors of cardiac involvement. The cut-off values discriminating cardiac involvement were 16.10% for GLS, 32.95% for GAS. During the median follow-up of 12.5 months (interquartile range 4–25 months), 20 (27%) patients died. For the Cox proportional model survival analysis, heart rate, cardiac troponin T, NT-proBNP levels, E/e’, GLS, and GAS were univariate predictors of death. Multivariate Cox model showed that GLS ≤ 14.78% and cardiac troponin T ≥ 0.049 mg/l levels were independent predictors of survival. Conclusions STE-3D measurements of LV myocardial mechanics could detect cardiac involvement in patients with AL amyloidosis; GLS and cardiac biomarkers can provided prognostic information for mortality prediction.

Background The correlations between genotype and phenotype in hypertrophic cardiomyopathy (HCM) have not been established. Mutation of α-actin gene (ACTC1) is a rare cause of HCM. This study aimed to explore novel genotype–phenotype correlations in HCM patients with the variants in ACTC1 and myosin-binding protein (MYBPC3) genes in three unrelated Chinese families. Methods Clinical, electrocardiographic, and echocardiographic examinations were performed in three Han pedigrees. Exon and boarding intron analysis of 96 cardio-disease-related genes was performed using second-generation sequencing on three probands. The candidate variants were validated in 14 available family members and 300 unrelated healthy controls by bi-directional Sanger sequencing. The pathogenicity and conservation were calculated using MutationTaster, PolyPhen-2, SIFT, and Clustal X. Pathogenicity classification of the variants was based on American College of Medical Genetics and Genomics (ACMG) guidelines. Results Nine members fulfilled diagnostic criteria for HCM with clinical characteristics, electrocardiographic, and echocardiographic findings. Two candidate variants in ACTC1 p.Asp26Asn (ACTC1-D26N) and MYBPC3 p.Arg215Cys (MYBPC3-R215C) were identified in patients. Only ACTC1-D26N strongly co-segregated with the HCM phenotype. Seven patients who harbored variant ACTC-D26N only were diagnosed with non-obstructive HCM, and four of these patients exhibited a triphasic left ventricular (LV) filling pattern. Two patients carrying both ACTC1-D26N and MYBPC3-R215C variants showed a higher LV outflow tract pressure gradient. Bioinformatics analysis revealed that the two variants were deleterious and highly conserved across species. According to ACMG guidelines, ACTC1-D26N is classified as a likely pathogenic mutation. The second variation MYBPC3-R215C may function as a genetic modifier, which remains uncertain here. Conclusions Novel p.(Asp26Asn) mutation of ACTC1 was associated with HCM phenotype, and the penetrance is extremely high (∼81.8%) in adults. The second variation, MYBPC3-R215C may function as a genetic modifier, which remains uncertain here.

Vitiligo is an acquired depigmentation skin disease caused by immune-mediated death of melanocytes. The most common treatment for vitiligo is narrow band ultraviolet B phototherapy, which often is combined with topical therapies such as tacrolimus. However, patients’ responses to these treatments show large variations. To date, the mechanism for this heterogeneity is unknown, and there are no molecular indicators that can predict an individual patient’s response to therapy. The goal of this study is to identify clinical parameters and gene expression biomarkers associated with vitiligo response to therapy. Six patients with segmental vitiligo and 30 patients with non-segmental vitiligo underwent transcriptome sequencing of lesional and nonlesional skin at baseline before receiving combined UBUVB and tacrolimus therapy for 6 month, and were separated into good response and bad response groups based on target lesion achieving > 10% repigmentation or not. Our study revealed that treatment-responsive vitiligo lesions had significantly shorter disease duration compared with non-responsive vitiligo lesions (2.5 years vs 11.5 years, p=0.046, t-Test), while showing no significant differences in the age, gender, ethnicity, vitiligo subtype, or disease severity. Transcriptomic analyses identified a panel of 68 genes separating the good response from bad response lesions including upregulation of immune active genes, such as CXCL10, FCRL3, and TCR, Further, compared with vitiligo lesions with long disease duration, the lesions with short duration also have much higher level of expression of immune-active genes, including some (such as FCRL3 and TCR genes) that are associated with favorable therapeutic response. In conclusion, our study has identified clinical parameters such as short disease duration and a panel of immune active and other gene expression biomarkers that are associated with favorable response to immune suppressive NBUVB + tacrolimus therapy. These markers may be useful clinically for individualized therapeutic management of vitiligo patients in the future.

Mitochondrial diseases constitute a group of heterogeneous hereditary diseases caused by impairments in mitochondrial oxidative phosphorylation and abnormal cellular energy metabolism. C1QBP plays an important role in mitochondrial homeostasis. In this study, clinical, laboratory examinations, 12-lead electrocardiographic, ultrasonic cardiogram, and magnetic resonance imaging data were collected from four members of a Chinese family. Whole exome were amplified and sequenced for the proband. The structure of protein encoded by the mutation was predicted using multiple software programs. The proband was a 14-year old boy with myocardial hypertrophy, exercise intolerance, ptosis, and increased lactate. His 9-year old brother exhibited similar clinical manifestations while the phenomenon of ptosis was not as noticeable as the proband. The onset of this disease was in infancy in both cases. They were born after uneventful pregnancies of five generation blood relative Chinese parents. A homozygous mutation (Leu275Phe) in the C1QBP gene was identified in both brothers in an autosomal recessive inherited pattern. Their parents were heterozygous mutation carriers without clinical manifestations. We demonstrated that a homozygous C1QBP- P.Leu275Phe mutation in an autosomal recessive inherited mode of inheritance caused early onset combined oxidative phosphorylation deficiency 33 (COXPD 33) (OMIM:617713) in two brothers from a Chinese family.

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).

Objectives: This study aimed to assess left ventricular (LV) energy loss (EL), circulation and vortex area using vector flow mapping (VFM) in patients with latent obstructive hyper­trophic cardiomyopathy (LOHCM) and nonobstructive hypertrophic cardiomyopathy (NOHCM). Methods: Fourteen LOHCM patients, 10 NOHCM patients, and 11 healthy individuals were evaluated by transthoracic echocardiography. An offline VFM workstation was used to analyze the LV blood flow patterns and fluid dynamics. The hemodynamic parameters, EL, circulation, and vortex area in 7 cardiac phases were calculated and analyzed. Results: Compared with controls and NOHCM patients, EL was significantly higher in ­LOHCM patients during the rapid ejection phase, slow ejection (SE) phase, and isovolumetric relaxation phase (p < 0.05). LOHCM patients also showed increased circulation during SE compared to the other two groups (p < 0.05). The ability to discriminate between NOHCM and LOHCM was assessed by the area under the receiver-operating characteristic curve (AUC), and EL during SE was found to have the largest AUC (0.964); the best cutoff value was 6.34 J/m3/s, with a sensitivity of 100% and specificity of 80%. Conclusions: The VFM technique can detect abnormal changes of LV EL and vortex characteristics in hypertrophic cardiomyopathy patients. Compared with controls and NOHCM patients, the LOHCM patients have worse systolic and diastolic functions.

To evaluate the efficacy and side effects of 1550-nm fractional Er:Glass laser in treating atrophic acne scar.Thirty Chinese patients aged 18-65 with atrophic acne scars on both cheeks received a split-face treatment, one side with four sessions of treatment with fractional 1550-nm Er:Glass laser at 20-day interval and the other with topical asiaticoside cream application three times daily as control. Clinical response and side effects were evaluated by a dermatologist three weeks after each treatment and again 12 weeks after the last laser treatment. In addition, self-evaluation of satisfaction by the patients was done at the end of treatment.The study found that mean scores decrease after treatment was 5.65 ± 4.34 for the treated side and 1.23 ± 3.41 for the control side. The improvement in acne scars after the fractional Er:Glass laser 1550-nm treatment was more significant than the control side (p = 0.0001). The side effects were mainly local skin irritation and erythema, which disappeared within one week.The research results show that the fractional 1550-nm Er:Glass laser is an effective and safe treatment device for atrophic acne scars.

Melasma is an acquired disorder of symmetrical hyperpigmentation commonly seen in patients with Fitzpatrick skin types III and IV. Various novel therapeutic modalities have emerged to treat melasma. The large-spot low-fluence QS Nd:YAG laser has been widely used in Asia; however, the modality needs to be optimized because of the high recurrence rate. The objective of this study is to explore the clinical efficacy and safety of fractional-mode (Pixel) Q-switched neodymium-doped yttrium aluminum garnet (Nd:YAG) 1064-nm laser for treatment of melasma in Chinese patients. Twenty-seven patients were enrolled and completed all the treatment sessions and the 12-week follow-up. All were treated using the fractional-mode Pixel QS Nd:YAG (1064 nm) laser for eight sessions at a 2–3-week interval. Clinical photographs were taken using the Visia skin analysis imaging system. Two blinded assessors evaluated melasma area and severity index (MASI) scores before and 4 weeks after the final session. Melanin index (MI) and erythema index (EI) was measured before each treatment visit and after the final treatment. The degree of pigmentation and erythema was assessed using a tristimulus color analyzer. Physicians’ global assessment (PGA) and patients’ self-assessment were taken as the subjective assessments. Wilcoxon signed-rank test was performed to evaluate clinical response. Recurrence rate were also evaluated. Mean MASI scores decreased from 12.84 ± 6.89 to 7.29 ± 4.15 after treatment (p = 0.000). Seventy percent of patients got moderate to good improvements after all the treatment. Mean MI decreased significantly from 56.52 ± 23.35 to 32.75 ± 12.91 (p = 0.000). L value increased from 59.21 ± 2.22 before treatment to 61.60 ± 2.40 (p = 0.000) after therapy. The mean score of PGA was 3.76 ± 0.71, indicating a “moderate” clearance of the lesion. In patients’ self-evaluations, 70 % of the patients rated the result as “good” to “remarkable.” Partial recurrence was seen in 40 % patients at the 3-month follow-up. No severe adverse events were observed during the study, and the treatment was well tolerated. The fractional mode (Pixel) QS Nd:YAG 1064-nm laser is an effective and safe treatment for melasma. The recurrence rate was relatively lower than that reported in studies treating with large-spot low-fluence QS Nd:YAG laser.