Construction of Immune-Related ceRNA Network in Dilated Cardiomyopathy: Based on Sex Differences.

Background: Immune targeted therapy has become an attractive therapeutic approach for patients with dilated cardiomyopathy (DCM) recently. Genetic predisposition and gender play a critical role in immune-related responses of DCM. This study aimed to perform a bioinformatics analysis of molecular differences between male and female samples and identify immune-related ceRNA network in DCM. Methods: The gene expression microarray and clinical features dataset of GSE19303 was downloaded from the GEO. The raw data were preprocessed, followed by identification of differentially expressed genes (DEGs) between male and female DCM samples. Crucial functions and pathway enrichment analysis of DEGs were investigated through GO analysis and KEGG pathway analysis, respectively. A lncRNA-miRNA-mRNA network was constructed and a central module was extracted from the ceRNA network. Results: Compared with the female group, the male group benefits more from IA/IgG immunotherapy. Male patients of DCM had a significant positive correlation with the abundance of inflammatory cells (B cells, memory B cells, CD8+ Tem cells, and NK cells). Sex difference DEGs had a widespread impact on the signaling transduction, transcriptional regulation, and metabolism in DCM. Subsequently, we constructed an immune-related ceRNA network based on sex differences in DCM, including five lncRNAs, six miRNAs, and 29 mRNAs. Furthermore, we extracted a central module from the ceRNA network, including two lncRNAs (XIST and LINC00632), three miRNAs (miR-1-3p, miR-17-5p, and miR-22-3p), and six mRNAs (CBL, CXCL12, ESR1, IGF1R, IL6ST, and STC1). Among these DEGs, CBL, CXCL12, and IL6ST expression was considered to be associated with inflammatory cell infiltration in DCM. Conclusions: The identified ceRNA network and their enriched pathways may provide genetic insights into the phenotypic diversity of female and male patients with DCM and may provide a basis for development of sex-related individualization of immunotherapy.

Associations of ATP-Sensitive Potassium Channel's Gene Polymorphisms With Type 2 Diabetes and Related Cardiovascular Phenotypes.

Type 2 diabetes (T2D) is characterized by increased levels of blood glucose but is increasingly recognized as a heterogeneous disease, especially its multiple discrete cardiovascular phenotypes. Genetic variations play key roles in the heterogeneity of diabetic cardiovascular phenotypes. This study investigates possible associations of ATP-sensitive potassium channel (KATP) variants with cardiovascular phenotypes among the Chinese patients with T2D. Six hundred thirty-six patients with T2D and 634 non-diabetic individuals were analyzed in the study. Nine KATP variants were determined by MassARRAY. The KATP rs2285676 (AA + GA, OR = 1.43, 95% CI: 1.13-1.81, P = 0.003), rs1799858 (CC, OR = 1.42, 95% CI: 1.12-1.78, P = 0.004), and rs141294036 (CC, OR = 1.45, 95% CI: 1.15-1.83, P = 0.002) are associated with increased T2D risk. A follow-up of at least 45.8-months (median) indicates further association between the 3 variants and risks of diabetic-related cardiovascular conditions. The associations are categorized as follows: new-onset/recurrent acute coronary syndrome (ACS) (rs2285676/AA + GA, HR = 1.37, 95% CI: 1.10-1.70, P = 0.005; rs141294036/TT + CT, HR = 1.59, 95% CI: 1.28-1.99, P < 0.001), new-onset stroke (rs1799858/CC, HR = 2.58, 95% CI: 1.22-5.43, P = 0.013; rs141294036/CC, HR = 2.30, 95% CI: 1.16-4.55, P = 0.017), new-onset of heart failure (HF) (rs1799858/TT + CT, HR = 2.78, 95% CI: 2.07-3.74, P < 0.001; rs141294036/TT + CT, HR = 1.45, 95% CI: 1.07-1.96, P = 0.015), and new-onset atrial fibrillation (AF) (rs1799858/TT + CT, HR = 2.05, 95% CI: 1.25-3.37, P = 0.004; rs141294036/CC, HR = 2.31, 95% CI: 1.40-3.82, P = 0.001). In particular, the CC genotype of rs1799858 (OR = 2.38, 95% CI: 1.11-5.10, P = 0.025) and rs141294036 (OR = 1.95, 95% CI: 1.04-3.66, P = 0.037) are only associated with the risk of ischemic stroke while its counterpart genotype (TT + CT) is associated with the risks of HF with preserved ejection fraction (HFpEF) (rs1799858, OR = 3.46, 95% CI: 2.31-5.18, P < 0.001) and HF with mildly reduced ejection fraction (HFmrEF) (rs141294036, OR = 2.74, 95% CI: 1.05-7.15, P = 0.039). Furthermore, the 3 variants are associated with increased risks of abnormal serum levels of triglyceride (TIRG) (≥ 1.70 mmol/L), low-density lipoprotein cholesterol (LDL-C) (≥ 1.40 mmol/L), apolipoprotein B (ApoB) (≥ 80 mg/dL), apolipoprotein A-I (ApoA-I) level (< 120 mg/dL), lipoprotein(a) Lp(a) (≥ 300 mg/dL) and high-sensitivity C-reactive protein (HsCRP) (≥ 3.0 mg/L) but exhibited heterogeneity (all P < 0.05). The KATP rs2285676, rs1799858, and rs141294036 are associated with increased risks of T2D and its related cardiovascular phenotypes (ACS, stroke, HF, and AF), but show heterogeneity. The 3 KATP variants may be promising markers for diabetic cardiovascular events favoring "genotype-phenotype" oriented prevention and treatment strategies.

Association of Digoxin Application Approaches With Long-Term Clinical Outcomes in Rheumatic Heart Disease Patients With Heart Failure: A Retrospective Study.

Objective: This retrospective, case-control study was executed to assess the effects of digoxin (DGX) use approaches [continuous use of DGX (cDGX) vs. intermittent use of DGX (iDGX)] on the long-term prognosis in rheumatic heart disease (RHD) patients with heart failure (HF). Methods: A total of 642 RHD patients were enrolled to this study after propensity matching. The associations of DGX application approaches with the risks of all-cause mortality, cardiovascular death (CVD), HF re-hospitalization (1-, 3-, and 5-year), and new-onset atrial fibrillation (AF) were analyzed by multivariate Cox proportional hazards or binary logistic regression models, respectively. Results: cDGX was associated with increased risks of all-cause mortality (adjusted HR = 1.84, 95% CI: 1.27-2.65, P = 0.001) and CVD (adjusted HR = 2.23, 95% CI: 1.29-3.83, P = 0.004) in RHD patients with HF compared to iDGX. With exception of 1-year HF re-hospitalization risk, cDGX was associated with increased HF re-hospitalization risk of 3-year (adjusted OR = 1.53, 95% CI: 1.03-2.29, P = 0.037) and 5-year (adjusted OR = 1.61, 95% CI: 1.05-2.50, P = 0.031) as well as new-onset AF (adjusted OR = 2.06, 95% CI: 1.09-3.90, P = 0.027). Conclusion: cDGX was significantly associated with increased risks of all-cause mortality, CVD, medium-/long-term HF re-hospitalization, and new-onset AF in RHD patients with HF.

Predictive value of serum myostatin for the severity and clinical outcome of heart failure.

BACKGROUND: The exact relationship between serum myostatin and the severity and prognosis of chronic heart failure (CHF) is unclear. In this study, we investigated the association between serum myostatin and the severity and prognosis in patients with CHF. METHODS: Two hundred and eighty-eight CHF patients and 62 healthy controls were studied. Cardiac ultrasound and serum myostatin, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and other parameters were detected. CHF patients were divided into 3 groups according to tertiles of NT-proBNP or myostatin levels respectively. RESULTS: Serum myostatin levels were higher in CHF patients than in controls. New York Heart Association (NYHA) class IV patients had the highest levels of serum myostatin among the four NYHA classes. Compared with the low tertile NT-proBNP group, serum myostatin levels were significantly higher in the moderate and high tertile groups (15.47 ±â€¯4.25 vs. 14.18 ±â€¯3.69 ng/mL, p = .026; 16.28 ±â€¯5.34 vs. 14.18 ±â€¯3.69 ng/mL, p = .002). During 51-months follow-up, of 173 patients there were 36 deaths. Compared to survivors, nonsurvivors had significantly higher serum myostatin (18.11 ±â€¯4.52 vs. 14.85 ±â€¯5.11 ng/mL, p < .01). Patients in the high tertile myostatin group had lower survival rate (73.95% vs. 93.75%; p < .05) and larger number of CHF rehospitalization than those in the low tertile group. Cox regression analysis showed that serum myostatin was an independent predictor of mortality. CONCLUSIONS: Serum myostatin levels can reflect the severity of CHF and be a predictor of adverse prognosis in CHF patients.

Effect of Diabetes on the Assessment Role of 2-Oxoglutarate to the Severity of Chronic Heart Failure.

BACKGROUND: Serum 2-oxoglutarate can reflect the severity of chronic heart failure (CHF) in patients without diabetes. Whether this predictive role persists in type 2 diabetes mellitus (T2DM) patients is unclear. In this study, we investigated this predictive role in T2DM patients and whether 2-oxoglutarate can indicate the diastolic or systolic function of left ventricle. METHODS: One hundred eighty CHF patients (76 with T2DM) and 66 healthy controls were studied. 2-Oxoglutarate was assayed by liquid chromatography-mass spectrometry/mass spectrometry. Echocardiographic parameters, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and other parameters were measured. RESULTS: 2-Oxoglutarate was increased in CHF patients with or without T2DM compared with controls (both P<0.01). Patients with a lower left ventricular ejection fraction or a higher NT-proBNP or left ventricular end-diastolic volume index had higher levels of 2-oxoglutarate (median, 18.77 µg/mL versus 11.25 µg/mL; median, 14.06 µg/ml versus 9.39 µg/ml; median, 18.06 µg/mL versus 11.60 µg/mL, all P<0.05) in nondiabetic patients but not in T2DM patients. In multiple logistic regression analysis, NT-proBNP (OR=3.445, 95% CI=1.098 to 10.816, P=0.034) and left ventricular end-diastolic diameter (OR=2.544, 95% CI=1.033 to 6.268, P=0.042) were independently associated with increased 2-oxoglutarate in nondiabetic patients. CONCLUSIONS: The levels of 2-oxoglutarate can reflect the clinical severity of CHF in nondiabetic patients but not in those with T2DM, and it can be used as a potential indicator of the systolic dysfunction of the left ventricle.

Treatment for Persistent Somatoform Pain Disorder via Electroacupuncture and a Low Dosage of Fluoxetine Hydrochloride.

CONTEXT: The clinical treatment of somatoform pain disorder (SPD) commonly combines antianxiety and antidepressant medication with pain medication, yet the method often entails a lengthy treatment, with uncertain outcomes, and, on occasion, significant side effects. Acupuncture can activate a patient's own pain control system, stimulate blood flow, repair the physical damage of emotional distress, reduce pain, lift mood, and boost the immune system. OBJECTIVE: The study intended to evaluate the benefits of adding a small dosage of fluoxetine hydrochloride (Prozac) to electroacupuncture treatment in the treatment of SPD. DESIGN: The research team performed an observational study. SETTING: The study took place at the 181st Hospital of the Chinese People's Liberation Army (Guilin, China). Participants: Participants were 64 patients who had been diagnosed with persistent SPD and who were being treated at the hospital. INTERVENTION: Participants received electroacupuncture treatment in 2 sets of points applied in 40-min sessions on alternating days, for 6 d of continuous treatment per wk, up to 8 wk. Participants were additionally treated with individualized points particular to each person's pain location. Participants also took 20 mg/d of fluoxetine hydrochloride for 8 wk. OUTCOME MEASURES: At baseline and at 1, 2, 4, and 8 wk of treatment, patients' degrees of pain, states of mind, and experiences of side effects were evaluated through the short-form McGill pain questionnaire. RESULTS: With regard to patients who had had trouble controlling chronic somatoform pain, the treatment with electroacupuncture to spots on the head, abdomen, waist, back, and sacrum, in conjunction with a light dosage of fluoxetine hydrochloride, showed reductions in pain, minimal side effects, and a low risk of relapse. CONCLUSIONS: Electroacupuncture, combined with a low dosage of fluoxetine hydrochloride, could be a beneficial treatment for chronic SPD. It avoids the risk of significant side effects from long-term ingestion of antianxiety and antidepressant medications, and the current research team has observed that it provides a relatively low likelihood of relapse. For patients with a history of untreatable persistent somatoform pain while using prescribed antianxiety and antidepression medication, the results can be rather satisfactory. It is hoped that these observations will direct further clinical research.

Free triiodothyronine levels and short-term prognosis in chronic heart failure patients with type 2 diabetes.

BACKGROUND: In chronic heart failure (CHF) patients with type 2 diabetes mellitus (T2DM), the role of thyroid hormone (TH) in predicting CHF severity and prognosis is unclear. The authors therefore investigated the role of TH in predicting CHF severity and prognosis in these specific patients. METHODS: A total of 224 CHF patients (114 with T2DM) over a mean follow-up time of 6.56 ± 0.18 months were studied. TH, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and other parameters were measured. RESULTS: Free triiodothyronine (FT3) levels were lower in the T2DM group compared with the nondiabetes group (P = 0.026) and higher in the New York Heart Association (NYHA) I group than in the NYHA III and IV groups (both P < 0.05). Compared with the low NT-proBNP group, the high NT-proBNP group had lower FT3 levels (P < 0.01). NT-proBNP correlated with NYHA classes (r = 0.541, P < 0.001), and inversely correlated with left ventricular ejection fraction (r = -0.431, P < 0.001) and FT3 levels (r = -0.335, P < 0.001). In multiple linear regression analysis, NT-proBNP was significantly correlated with NYHA classes (P < 0.001), left ventricular ejection fraction (P < 0.001) and FT3 (P = 0.004). Kaplan-Meier curves showed that the low FT3 group had an increased rate of short-term adverse outcomes of CHF (log rank, χ = 9.794, P = 0.002). CONCLUSIONS: FT3 levels are associated with the severity of CHF and seem to reflect short-term outcomes in CHF patients with T2DM.

Correlation of virtual touch tissue quantification and liver biopsy in a rat liver fibrosis model.

Liver fibrosis assessment is very important to the treatment of chronic liver disease. In the present study, Virtual Touch Tissue Quantification (VTQ) and eSie Touch™ elasticity imaging techniques were used to examine the rat liver fibrosis model. Rat liver fibrosis was induced with thioacetamide and the degree of liver fibrosis was determined using pathological diagnosis as a gold standard. The right lobe of the liver was also examined with the VTQ and eSie Touch™ techniques. The VTQ and serological results were correlated and analyzed. The results were compared with those obtained from liver biopsies to investigate the accuracy and diagnostic value of eSie Touch™ and VTQ on the classification of liver fibrosis in rats. A total of 30 successful modeling cases were obtained, with a success rate of 86%. The mean acoustic radiation force impulse (ARFI) elastography­VTQ values were 1.08, 1.51, 1.88 and 2.50 m/sec for the normal and F1/F2, F3 and F4 fibrosis groups, respectively. A significant correlation (r = 0.969) was identified between the ARFI measurements and the degree of fibrosis assessed by pathological examination (P<0.001). The histological staging results correlated with those of the eSie Touch™ elasticity imaging of the biopsy site (r = 0.913, P<0.001). The predictive values of ARFI for various stages of fibrosis were as follows: F≥1 and 2 ­ cut­off >1.250 m/sec (when Vs >1.250 m/sec, the pathological grading was ≥F1/F2) [Area under receiver operating characteristic (AUROC) = 1.00], F≥3 ­ cut­off >1.685 m/sec (when Vs >1.685 m/sec, the pathological grading was ≥F3; AUROC = 1.00) and F≥4 ­ cut­off >2.166 m/sec (when Vs >2.166 m/sec, the pathological grading is cirrhosis; AUROC = 1.00). In conclusion, the eSie Touch™ elasticity imaging and VTQ techniques may be successfully adopted to assess the extent of liver stiffness. These techniques are expected to replace liver biopsy.

Increased serum 2-oxoglutarate associated with high myocardial energy expenditure and poor prognosis in chronic heart failure patients.

Myocardial energy expenditure (MEE) and 2-oxoglutarate are elevated in chronic heart failure (CHF) patients compared with healthy controls. To explore whether 2-oxoglutarate could reflect the levels of MEE and predict the prognosis of CHF, 219 CHF patients and 66 healthy controls were enrolled. 2-Oxoglutarate was assayed with Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC/MS/MS). CHF patients were divided into 4 groups according to interquartile range of MEE and followed for death or recurrent hospital admission due to CHF for the mean follow-up time 6.64±0.16months. 2-Oxoglutarate was increased in CHF patients compared with controls (P<0.01) and correlated with estimated glomerular filtration rate (r=0.142, P=0.036), age (r=-0.269, P<0.01) and MEE levels (r=0.307, P<0.01) in a multiple linear correlation analysis in CHF patients. Furthermore, 2-oxoglutarate (OR=3.470, 95% CI=1.557 to 7.730, P=0.002), N-terminal pro-B-type natriuretic peptide (OR=4.013, 95% CI=1.553 to 10.365, P=0.004), age (OR=1.611, 95% CI=1.136 to 2.283, P=0.007) and left ventricular ejection fraction (OR=7.272, 95% CI=3.110 to 17.000, P<0.001) were independently associated with MEE on multiple logistic regression analysis. Kaplan-Meier event curves showed that high 2-oxoglutarate levels were associated with adverse outcomes (Log Rank, Chi(2)=4.026, P=0.045). This study showed that serum 2-oxoglutarate is associated with MEE levels, which can be used as potential biomarkers for MEE, and it can reflect the clinical severity and short-term outcome of CHF.

Late hematoma, seroma, and galactocele in breasts injected with polyacrylamide gel.

Late hematoma or seroma and galactocele caused by augmentation mammaplasty have been reported in patients with silicon breast prostheses but are extremely rare in patients injected with polyacrylamide gel (PAAG). In a retrospective survey, the incidence, clinical manifestations, and management of late hematoma, seroma, and galactocele in 28 of 2,610 patients who underwent breast augmentation with PAAG injection were investigated, and 5 typical cases are presented. The diagnostic and managing methods for this complication have been assessed. The incidence of late hematoma or seroma was 0.65% and that of galactocele was 0.35% among patients with PAAG-injected breast augmentations. The clinical onsets of such late PAAG complications were of two types: rapid enlargement in 17 patients and progressive expansion in another 11 patients. Aspiration, ultrasound, and magnetic resonance imaging (MRI) are useful and sensitive tools for diagnosis. Foreign body reaction, PAAG-related tissue necrosis and fibrosis, and granuloma were shown, and the bacterial cultures in all 12 cases were negative. Needle aspiration with pressure dressing has been advocated as a reliable method for small diseases, and surgical exploration with irrigation-vacuum drainage and evacuation with capsulectomy have been considered more effective for recurrent, large, and long-term cases. In conclusion, these late complications rarely present after large-volume injections of PAAG for breast augmentation. The PAAG-related pathologic inflammatory tissue changes are suggested as the pathogenesis for the complication. Trauma and breastfeeding are considered to be stimulating factors.

[Nasendoscopic comparison for cleft palate repair after velopharyngeal muscle reconstruction].

OBJECTIVE: To find out the nasendoscopic changes of velopharyngeal configuration and movement after palatoplasty with or without velopharyngeal muscle reconstruction. METHODS: The nasendoscopy was taken in forty-one patients with palatoplasty, 22 repaired by velopharyngeal muscle reconstruction and 19 with modified von Langenbeck's procedure (non-reconstructive group). RESULTS: In patients with velopharyngeal muscle reconstruction, the velopharyngeal ports are smooth and full with a definite reduction in size than patients without velopharyngeal muscle reconstruction. During phonation, the complete and marginal velopharyngeal competence rate in reconstructive group (90.91%) is higher than the group of non-reconstruction (37.31%) The major velopharyngeal closure is circular movement in reconstructive group, otherwise coronal closure in nonconstructive group. CONCLUSIONS: Based the observation of nasendoscopy, the velopharyngeal muscle reconstruction in palatoplasty has more definite improvement to velopharyngeal closure than non-reconstructive procedure. Palatoplasty with velopharyngeal muscle reconstruction could reduce the size of velopharyngeal port and make the complete velopharyngeal closure easier.

Migration of implants: a problem with injectable polyacrylamide gel in aesthetic plastic surgery.

Polyacrylamide gel (PAAG) has been used as a soft tissue filler material for cosmetic purposes in Europe and China since 1997. The various complications of PAAG have been reported. A total of 15 patients who received PAAG injections at other institutions were treated for gel migration in the authors' hospitals. During treatment, the authors found that the injected PAAG had not formed capsules within the muscle and was encapsulated only by thin fibrous tissue in skin and mammary glands. Consequently, the filler material migrated easily because of muscular activity or the influence of gravity, especially when the capsule was broken by incorrect massage or incidental force. It is suggested that PAAG should not be injected into muscular tissue or subcutaneous areas with active movement, such as joints and muscles involved in facial expression with thin skin. After years of gel implantation, the thinned capsule may result in an increasing incidence of this complication. Management and some clinical findings in relation to the complication also are discussed.