LncRNA-Gm9866 promotes liver fibrosis by activating TGFß/Smad signaling via targeting Fam98b.

OBJECTIVE: The exact mechanism and target molecules of liver fibrosis have remained largely elusive. Here, we investigated the role of long noncoding RNA Gm9866(lncRNA-Gm9866) on liver fibrosis. METHODS: The transcription of lncRNA-Gm9866 in activated cells and mouse fibrotic livers was determined by quantitative polymerase chain reaction (qRT-PCR). The effects of lentivirus-mediated knockdown or overexpression of lncRNA-Gm9866 in liver fibrosis were examined in vitro and in vivo. Furthermore, bioinformatics analysis, cell samples validation, fluorescence in situ hybridization (FISH) co-localization, RNA binding protein immunoprecipitation (RIP), actinomycin D test and Western blot (WB) were carried out to explore the potential mechanism of lncRNA-Gm9866. RESULTS: The expression of α-smooth muscle actin (α-SMA), Collagen I (COL-1) and lncRNA-Gm9866 were significantly increased in tissues and cells. Overexpressing lncRNA-Gm9866 promoted the activation of hepatic stellate cells (HSCs). Silencing lncRNA-Gm9866 inhibited the activation of HSCs and transforming growth factor-ß1 (TGFß1) induced fibrosis. Overexpressing lncRNA-Gm9866 promoted hepatocytes (HCs) apoptosis and the expression of pro-fibrogenic genes, inhibited the proliferation and migration of HCs. Knockdown of lncRNA-Gm9866 inhibited the apoptosis of HCs, the expression of pro-fibrogenic genes, TGFß1 induced fibrosis and the occurrence of carbon tetrachloride (CCl4)-induced liver fibrosis, and promoted the proliferation and migration of HCs. Mechanistically, lncRNA-Gm9866 may directly bine with Fam98b. Silencing Fam98b in stably overexpressing lncRNA-Gm9866 cell lines reversed the increase of pro-fibrogenic genes and pro-apoptotic genes, fibrosis related pathway protein TGFß1, Smad2/3, p-Smad2/3 and Notch3 induced by overexpressing lncRNA-Gm9866. CONCLUSIONS: LncRNA-Gm9866 may regulate TGFß/Smad and Notch pathways by targeting Fam98b to regulate liver fibrosis. LncRNA-Gm9866 may be a new target for diagnosis and treatment of liver fibrosis.

Development and Validation of an Electronic Frailty Index Using Routine Electronic Health Records: An Observational Study From a General Hospital in China.

Background: This study aimed to develop and validate an electronic frailty index (eFI) based on routine electronic health records (EHR) for older adult inpatients and to analyze the correlations between frailty and hospitalized events and costs. Methods: We created an eFI from routine EHR and validated the effectiveness by the consistency of the comprehensive geriatric assessment-frailty index (CGA-FI) with an independent prospective cohort. Then, we analyzed the correlations between frailty and hospitalized events and costs by regressions. Results: During the study period, 49,226 inpatients were included in the analysis, 42,821 (87.0%) of which had enough data to calculate an eFI. A strong correlation between the CGA-FI and eFI was shown in the validation cohort of 685 subjects (Pearson's r = 0.716, P < 0.001). The sensitivity and specificity for an eFI≥0.15, the upper tertile, to identify frailty, defined as a CGA-FI≥0.25, were 64.8 and 88.7%, respectively. After adjusting for age, sex, and operation, an eFI≥0.15 showed an independent association with long hospital stay (odds ratio [OR] = 2.889, P < 0.001) and death in hospital (OR = 19.97, P < 0.001). Moreover, eFI values (per 0.1) were positively associated with total costs (ß = 0.453, P < 0.001), examination costs (ß = 0.269, P < 0.001), treatment costs (ß = 0.414, P < 0.001), nursing costs (ß = 0.381, P < 0.001), pharmacy costs (ß = 0.524, P < 0.001), and material costs (ß = 0.578, P < 0.001) after adjusting aforementioned factors. Conclusions: We successfully developed an effective eFI from routine EHR from a general hospital in China. Frailty is an independent risk factor for long hospital stay and death in hospital. As the degree of frailty increases, the hospitalized costs increase accordingly.

Performance of Prognostic Risk Scores in Elderly Chinese Patients with Heart Failure.

PURPOSE: Elderly heart failure (HF) patients have different clinical characteristics and poorer prognosis compared with younger patients. Prognostic risk scores for HF have not been validated well in elderly patients. We aimed to validate the Seattle Heart Failure Model (SHFM) and the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score in an elderly Chinese HF cohort. PATIENTS AND METHODS: This retrospective study enrolled 675 elderly HF patients (age≥70 years) discharged from our hospital between 2012 and 2017. The performance of the two risk scores was evaluated in terms of discrimination, using receiver-operating characteristic analysis, and calibration using a calibration plot and Hosmer-Lemeshow (H-L) test. Absolute risk reclassification was used to compare the two scores. RESULTS: During the mean follow-up time of 32.6 months, 193 patients (28.6%) died, and 1-year mortality was 10.5%. The predicted median 1-year mortality was 8% for the SHFM and 18% for the MAGGIC score. A Kaplan-Meier survival curve demonstrated that event rates of all-cause mortality significantly increased with increasing SHFM and MAGGIC scores. The discriminatory capacity of the SHFM was greater than that of the MAGGIC score (c-statistics were 0.72 and 0.67, respectively; P = 0.05). The calibration plot for the SHFM was better than that for MAGGIC score for 1-year mortality (SHFM: H-L χ2 =8.2, P = 0.41; MAGGIC: H-L χ2 =18.8, P =0.02). Compared with the MAGGIC score, the net reclassification index (NRI) of the SHFM was 2.96% (Z=5.88, P< 0.0001). CONCLUSION: The SHFM performs better than MAGGIC score, having good discrimination, calibration and risk classification for the prediction of 1-year mortality in elderly Chinese HF patients.

Myocardial Tissue Reverse Remodeling After Guideline-Directed Medical Therapy in Idiopathic Dilated Cardiomyopathy.

BACKGROUND: The prognosis of patients with idiopathic dilated cardiomyopathy (DCM) has improved remarkably in recent decades with guideline-directed medical therapy. Left ventricular (LV) reverse remodeling (LVRR) is one of the major therapeutic goals. Whether myocardial fibrosis or inflammation would reverse associated with LVRR remains unknown. METHODS: A total of 157 prospectively enrolled patients with DCM underwent baseline and follow-up cardiovascular magnetic resonance examinations with a median interval of 13.7 months (interquartile range, 12.2-18.5 months). LVRR was defined as an absolute increase in LV ejection fraction of >10% to the final value of ≥35% and a relative decrease in LV end-diastolic volume of >10%. Statistical analyses were performed using paired t test and student t test, logistic regression analysis, and linear regression analysis. RESULTS: Forty-eight (31%) patients reached LVRR. At baseline, younger age, worse New York Heart Association class, new-onset heart failure, lower LV ejection fraction, absence of late gadolinium enhancement, lower myocardial T2, and extracellular volume were significant predictors of LVRR. During the follow-up, patients with and without LVRR both showed a significant decrease of myocardial native T1 (LVRR: [baseline] 1303.0±43.6 ms; [follow-up] 1244.7±51.8 ms; without LVRR: [baseline] 1308.5±80.5 ms; [follow-up] 1287.6±74.9 ms, both P<0.001), matrix and cellular volumes while no significant difference was observed in T2 or extracellular volume values after treatment. CONCLUSIONS: In patients with idiopathic DCM, the absence of late gadolinium enhancement, lower T2, and extracellular volume values at baseline are significant predictors of LVRR. The myocardial T1, matrix, and cell volume decrease significantly in patients with LVRR after guideline-directed medical therapy. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: ChiCTR1800017058.

Prognostic value of left ventricular remodelling index in idiopathic dilated cardiomyopathy.

AIMS: To evaluate the prognostic value of left ventricular (LV) remodelling index (RI) in idiopathic dilated cardiomyopathy (DCM) patients. METHODS AND RESULTS: We prospectively enrolled 412 idiopathic DCM patients and 130 age- and sex-matched healthy volunteers who underwent cardiovascular magnetic resonance imaging between September 2013 and March 2018. RI was defined as the cubic root of the LV end-diastolic volume divided by the mean LV wall thickness on basal short-axis slice. The primary endpoint included all-cause mortality and heart transplantation. The secondary endpoint included the primary endpoint and heart failure (HF) readmission. During the median follow-up of 28.1 months (interquartile range: 19.3-43.0 months), 62 (15.0%) and 143 (34.7%) patients reached the primary and secondary endpoints, respectively. Stepwise multivariate Cox regression showed that RI [hazard ratio (HR) 1.20, 95% confidence interval (CI) 1.11-1.30, P < 0.001], late gadolinium enhancement (LGE) presence and log (N-terminal pro-B-type natriuretic peptide) were independent predictors of the primary endpoint, while RI (HR 1.15, 95% CI 1.08-1.23, P < 0.001) and extracellular volume were independent predictors of the secondary endpoint. The addition of RI to LV ejection fraction (EF) and LGE presence showed significantly improved global χ2 for predicting primary and secondary endpoints (both P < 0.001). Furthermore, RI derived from echocardiography also showed independent prognostic value for primary and secondary endpoints with clinical risk factors. CONCLUSIONS: RI is an independent predictor of all-cause mortality, heart transplantation, and HF readmission in DCM patients and provides incremental prognostic value to LVEF and LGE presence.

Predicting non-elective hospital readmission or death using a composite assessment of cognitive and physical frailty in elderly inpatients with cardiovascular disease.

BACKGROUND: We aimed to assess the utility of the combination of the mini-mental state examination (MMSE) + clock drawing test (CDT) and the Fried phenotype for predicting non-elective hospital readmission or death within 6 months in elderly inpatients with cardiovascular disease (CVD). METHODS: A single-center prospective cohort was conducted from September 2018 to February 2019. Inpatients ≥65 years old were recruited. Predictive validity was tested using a Cox proportional hazards regression model analysis, and the discriminative ability was evaluated by the receiver operating characteristic (ROC) curve. RESULTS: A total of 542 patients were included. Overall, 12% (64/542) screened positive for cognitive impairment, 16% (86/542) were physically frail and 8% (44/542) had cognitive impairment combined with physical frailty, showing an older age (P < 0.001) and a lower education level (P < 0.001) than physically frail patients. A total of 113 patients (20.9%) died or were readmitted at 6 months. Frail participants with a normal (hazard ratio [HR]: 1.73, 95% confidence interval [CI]: 1.06-2.82, P = 0.028) or impaired cognition (HR: 2.50, 95% CI: 1.27-4.91, P = 0.008) had a higher risk of non-elective hospital readmission or death than robust patients after adjusting for the age, sex, education level, marital status, the presence of diabetes mellitus, heart failure, and history of stroke. The area under the ROC curve (AUC) showed that the discriminative ability in relation to 6 months readmission and death for the MMSE + CDT + Fried phenotype was 0.65 (95% CI: 0.60-0.71), and the AUC for men was 0.71 (95% CI: 0.63-0.78), while that for women was 0.60 (95% CI: 0.51-0.69). CONCLUSIONS: Accounting for cognitive impairment in the frailty phenotype may allow for the better prediction of non-elective hospital readmission or death in elderly inpatients with CVD in the short term. TRIAL REGISTRATION: ChiCTR1800017204; date of registration: 07/18/2018.

Urinary 8-oxo-7,8-dihydroguanosine as a potential biomarker of frailty for elderly patients with cardiovascular disease.

The diagnosis of frailty is usually subjective, which calls for objective biomarkers in clinical medicine. 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGsn) and 8-oxo-7, 8-dihydroguanosine (8-oxoGsn) in urine are two aging biomarkers that have not been explored deeply in cases of frailty. A total of 508 elderly patients with cardiovascular disease (mean age 75.0 ± 6.5 years, 50.8% males) were enrolled consecutively. Frailty was assessed by the Fried phenotype (robust: 0 score; pre-frail: 1-2 scores; frail: 3-5 scores). The concentrations of 8-oxoGsn and 8-oxodGsn in urine were measured by improved ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Urinary creatinine (Cre) was tested to correct the 8-oxoGsn and 8-oxodGsn levels. According to the Fried phenotype score, the proportions of robust, pre-frail, and frail subjects were 20.5% (104/508), 53.9% (274/508), and 25.6% (130/508), respectively. The urinary 8-oxoGsn/Cre (P < 0.001) differed significantly among these 3 groups, but the urinary 8-oxodGsn/Cre (P = 0.600) showed no marked difference. Univariate and multivariate logistic regression showed that the age (odds ratio [OR] = 1.090, P < 0.001), systolic blood pressure (OR = 0.981, P = 0.008), 8-oxoGsn/Cre (OR = 1.203, P = 0.007), hemoglobin (OR = 0.980, P = 0.007), and sodium (OR = 0.915, P = 0.044) were independently associated with frailty. The sensitivity and specificity to identify frailty were 53.08% and 71.96%, respectively, for 8-oxoGsn/Cre at the optimal cut-off value of 3.879 µmol/mol according to the maximal Youden index. Urinary 8-oxoGsn, as a recognized biomarker of RNA oxidation, is independently associated with frailty in elderly patients with cardiovascular disease. However, the urinary 8-oxodGsn shows no obvious correlation with frailty. To obtain a better diagnostic performance for frailty, more biomarkers from different pathophysiological pathways should be explored in the future.

Left ventricular function recovery in peripartum cardiomyopathy: a cardiovascular magnetic resonance study by myocardial T1 and T2 mapping.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is rare and potentially life-threatening; its etiology remains unclear. Imaging characteristics on cardiovascular magnetic resonance (CMR) and their prognostic significance have rarely been studied. We sought to determine CMR's prognostic value in PPCM by using T1 and T2 mapping techniques. METHODS: Data from 21 PPCM patients from our CMR registry database were analyzed. The control group comprised 20 healthy age-matched females. All subjects underwent comprehensive contrast-enhanced CMR. T1 and T2 mapping using modified Look-Locker inversion recovery and T2 prep balanced steady-state free precession sequences, respectively. Ventricular size and function, late gadolinium enhancement (LGE), myocardial T1 value, extracellular volume (ECV), and T2 value were analyzed. Transthoracic echocardiography was performed at baseline and during follow-up. The recovered left ventricular ejection fraction (LVEF) was defined as LVEF ≥50% on echocardiography follow-up after at least 6 months of the diagnosis. RESULTS: CMR imaging showed that the PPCM patients had severely impaired LVEF and right ventricular ejection fraction (LVEF: 26.8 ± 10.6%; RVEF: 33.9 ± 14.6%). LGE was seen in eight (38.1%) cases. PPCM patients had significantly higher native T1 and ECV (1345 ± 79 vs. 1212 ± 32 ms, P < 0.001; 33.9 ± 5.2% vs. 27.1 ± 3.1%, P < 0.001; respectively) and higher myocardial T2 value (42.3 ± 3.7 vs. 36.8 ± 2.3 ms, P < 0.001) than did the normal controls. After a median 2.5-year follow-up (range: 8 months-5 years), six patients required readmission for heart failure, two died, and 10 showed left ventricular function recovery. The LVEF-recovered group showed significantly lower ECV (30.7 ± 2.1% vs. 36.8 ± 5.6%, P = 0.005) and T2 (40.6 ± 3.0 vs. 43.9 ± 3.7 ms, P = 0.040) than the unrecovered group. Multivariable logistic regression analysis showed ECV (OR = 0.58 for per 1% increase, P = 0.032) was independently associated with left ventricular recovery in PPCM. CONCLUSIONS: Compared to normal controls, PPCM patients showed significantly higher native T1, ECV, and T2. Native T1, ECV, and T2 were associated with LVEF recovery in PPCM. Furthermore, ECV could independently predict left ventricular function recovery in PPCM.

Identification of Frailty and Its Risk Factors in Elderly Hospitalized Patients from Different Wards: A Cross-Sectional Study in China.

OBJECTIVES: To survey the difference of frailty prevalence in elderly inpatients amongdifferent wards; to compare the diagnostic performance of five frailty measurements (Clinical Frailty Scale [CFS], FRAIL, Fried, Edmonton, Frailty Index [FI]) in identifying frailty; and to explore the risk factors of frailty in elderly inpatients. PARTICIPANTS AND METHODS: This was a cross-sectional study including 1000 inpatients (mean age 75.2±6.7 years, 51.5% male; 542, 229, and 229 patients from cardiology, non-surgical, and surgical wards, respectively) in a tertiary hospital from September 2018 to February 2019. We applied the combined index to integrate the five frailty measurements mentioned above as the gold standard of frailty diagnosis. Multivariate logistic regression models were used to determine the independent risk factors of frailty. RESULTS: Frailty prevalence was 32.3% (Fried), 36.2% (CFS), 19.2% (FRAIL), 25.2% (Edmonton), 35.1% (FI) in all patients. The frailty was more common in non-surgical wards, regardless of the frailty assessment tools used (non-surgical wards: 27.5% to 51.5%; cardiology ward: 14.9% to 29.3%; surgical wards: 18.8% to 41.9%). CFS≥5 showed a sensitivity of 94.1% and a specificity of 85.2% for all patients. FI≥0.25 showed a sensitivity of 94.8% and a specificity of 87.0% for all patients. Age [odds ratio (OR) = 1.089, P<0.001], education level (OR = 0.782, P=0.001), heart rate (OR = 1.025, P<0.001), albumin (OR = 0.911, P=0.002), log D-dimer (OR = 2.940, P<0.001), ≥5 comorbidities (OR = 2.164, P=0.002), and ≥5 medications (OR = 2.819, P<0.001) were independently associated with frailty in all participants. CONCLUSION: Frailty is common among elderly inpatients, especially in non-surgical wards. CFS is a preferred screening tool and FI may be an optimal assessment tool. Old age, low educational level, fast heart rate, low albumin, high D-dimer, ≥5 comorbidities, and polypharmacy are independent risk factors of frailty in elderly hospitalized patients.

Post-discharge short message service improves short-term clinical outcome and self-care behaviour in chronic heart failure.

AIMS: In addition to giving optimal medical and device therapy, promoting self-care of chronic heart failure (CHF) patients also plays an important role in comprehensive disease management for better outcomes. The study was aimed to investigate whether short message service (SMS) would help to improve death or readmission-free survival and self-care behaviour in CHF patients. METHODS AND RESULTS: This was a randomized controlled trial. Between December 2011 and September 2015, patients admitted with decompensated CHF in a tertiary referral hospital who fulfilled the inclusion criteria were enrolled and randomized to receive SMS, structured telephone support (STS), or usual care after discharge. All patients were followed up to 180 days after discharge by phone call or clinic visit. Primary endpoint was the 180 day composite event, defined as all-cause mortality or readmission. Secondary endpoints included self-care behaviour and quality of life. Seven hundred sixty-seven patients (61 ± 15 years, 56.5% male) were finally randomized to receive SMS (n = 252), STS (n = 255), or usual care (n = 260). Baseline characteristics were similar among the three groups. Five hundred twenty-five (68.4%) patients were in New York Heart Association Class III or IV, and 472 (61.5%) patients had an ejection fraction of <50%. During a 180 day follow-up, 76 (9.9%) patients died and 274 (35.7%) patients experienced at least one readmission. In a short-term follow-up of 30 days, there was no difference in mortality and the composite endpoint among the three groups (SMS vs. STS vs. usual care: 2.8% vs. 3.1% vs. 3.8% for mortality, P = 0.786; 12.3% vs. 14.5% vs. 15.4% for the composite endpoint, P = 0.588). The 180 day composite event rate was significantly lower in the SMS and STS groups (50.4% vs. 41.3% and 36.5%, both P < 0.05) than in the usual care group, but no difference was observed between the two phone-based intervention groups (P = 0.268). Although there was no difference between the two groups, better self-care behaviour was reported in the SMS and STS groups than in the control group (medication compliance, 78.9% vs. 81.4% vs. 69.5%, P = 0.011; water restriction, 70.8% vs. 74.5% vs. 61.5%, P = 0.013). Quality-of-life score was similar among the three groups at 180 days (P = 0.526). CONCLUSIONS: In CHF patients, post-discharge SMS, which appeared as efficient as STS, reduced the 180 day composite event and improved self-care behaviour. SMS intervention could be integrated into CHF management.

Caregiving burden and depression in paid caregivers of hospitalized patients: a pilot study in China.

BACKGROUND: Caregiving burden and depression in family caregivers have been investigated, but little is known about how they affect paid caregivers. The aim of this study was to investigate caregiving burden and depression in paid caregivers of hospitalized patients. METHODS: A cross-sectional survey study was conducted in a tertiary referral hospital (Chengdu, China) that enrolled 108 paid caregivers who worked in the inpatient department. The Caregiver Burden Inventory (CBI) and the Center for Epidemiologic Studies Depression (CES-D) scale were incorporated into a self-developed questionnaire to gather demographic information on the following four aspects: general, work, income, and family. RESULTS: The mean total CBI score was 29.7 ± 12.5. The time-dependence burden had the highest score of 15.3 ± 4.0, which was followed by the physical burden score of 6.5 ± 4.6, developmental burden score of 3.7 ± 4.0, social burden score of 3.2 ± 4.0, and emotional burden score of 2.4 ± 3.1. Multiple linear regression analysis showed that a higher CBI was associated with a longer time as a paid caregiver [ß=7.041, 95% Confidence Interval (CI):1.935 to 12.974, p = 0.009], lower income satisfaction (ß= - 6.573, 95% CI: -11.248 to -3.020, p = 0.001), and higher frequency of meeting with their relatives (ß=7.125, 95% CI: 2.019 to 12.456, p = 0.006). The mean CES-D score was 11.9 ± 8.7, and significant depression was found in 28 (25.9%) paid caregivers according to the CES-D score ≥ 16 cut-off. There was a moderate positive correlation between the CBI and CES-D scores (Pearson's r = 0.452, p < 0.001). CONCLUSIONS: A high caregiving burden was commonly observed in paid caregivers of hospitalized patients in China, as was a high prevalence of depression symptoms. Several associated factors were identified that could be areas for future interventions.