Efficacy of Sacubitril-Valsartan on Survival and Cardiac Remodeling in Hypotensive Heart Failure With Reduced Ejection Fraction: A Multicenter Study.

OBJECTIVE: To investigate whether hypotensive patients diagnosed with heart failure and reduced ejection fraction (HFrEF) might benefit from angiotensin receptor-neprilysin inhibitors (ARNis) in real-world practice because patients with baseline systolic blood pressure (SBP) of less than 100 mm Hg have been excluded from landmark trials. PATIENTS AND METHODS: In this multicenter study conducted between January 1, 2013, and December 31, 2021, a total of 7562 symptomatic patients with HFrEF were enrolled and grouped by SBP (hypotension was defined as an SBP of less than 100 mm Hg) and ARNi use as follows: group 1, hypotensive/non-ARNi users (n=484); group 2, hypotensive/ARNi users (n=308); group 3, nonhypotensive/non-ARNi users (n=4560); and group 4, nonhypotensive/ARNi users (n=2210). Inverse probability of treatment weighting was used to balance baseline characteristics for survival analysis. RESULTS: Diverse baseline characteristics and lower rates of medication use were found among non-ARNi users compared with ARNi users. Hypotensive/ARNi users had lower ARNi initiation doses than nonhypotensive/ARNi users. We observed significantly lower mortality, composite heart failure hospitalization, and CV death for hypotensive/ARNi and the other 2 nonhypotensive groups (groups 3 and 4) during a median follow-up of 3.43 years (all P<.05), with a similar effect on reverse remodeling for the hypotensive/ARNi group compared with the hypotensive/non-ARNi group. The event-free survival benefits of ARNi vs renin-angiotensin system inhibitors were consistent with the lower boundary of SBP for clinical benefits found until 88 mm Hg (spline curves) after inverse probability of treatment weighting. CONCLUSION: Patients with HFrEF and hypotension may still benefit from ARNi treatment. Patients with hypotensive HFrEF should not be routinely excluded from ARNi use in a real-world setting.

Single-cell and spatial architecture of primary liver cancer.

Primary liver cancer (PLC) poses a leading threat to human health, and its treatment options are limited. Meanwhile, the investigation of homogeneity and heterogeneity among PLCs remains challenging. Here, using single-cell RNA sequencing, spatial transcriptomic and bulk multi-omics, we elaborated a molecular architecture of 3 PLC types, namely hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular-cholangiocarcinoma (CHC). Taking a high-resolution perspective, our observations revealed that CHC cells exhibit internally discordant phenotypes, whereas ICC and HCC exhibit distinct tumor-specific features. Specifically, ICC was found to be the primary source of cancer-associated fibroblasts, while HCC exhibited disrupted metabolism and greater individual heterogeneity of T cells. We further revealed a diversity of intermediate-state cells residing in the tumor-peritumor junctional zone, including a congregation of CPE+ intermediate-state endothelial cells (ECs), which harbored the molecular characteristics of tumor-associated ECs and normal ECs. This architecture offers insights into molecular characteristics of PLC microenvironment, and hints that the tumor-peritumor junctional zone could serve as a targeted region for precise therapeutical strategies.

2023 HRS/EHRA/APHRS/LAHRS Expert Consensus Statement on Practical Management of the Remote Device Clinic.

Remote monitoring is beneficial for the management of patients with cardiovascular implantable electronic devices by impacting morbidity and mortality. With increasing numbers of patients using remote monitoring, keeping up with higher volume of remote monitoring transmissions creates challenges for device clinic staff. This international multidisciplinary document is intended to guide cardiac electrophysiologists, allied professionals, and hospital administrators in managing remote monitoring clinics. This includes guidance for remote monitoring clinic staffing, appropriate clinic workflows, patient education, and alert management. This expert consensus statement also addresses other topics such as communication of transmission results, use of third-party resources, manufacturer responsibilities, and programming concerns. The goal is to provide evidence-based recommendations impacting all aspects of remote monitoring services. Gaps in current knowledge and guidance for future research directions are also identified.

Risk stratification for worsening renal function and renal decline in heart failure patients with reduced ejection fraction after sacubitril/valsartan treatment.

BACKGROUND: In the real-world setting, data regarding renal decline following sacubitril/valsartan treatment are lacking. This study aimed to develop a scoring system to predict renal outcome in sacubitril/valsartan-treated patients. METHODS: Between 2017 and 2018, a total of 1505 heart failure patients with reduced ejection fraction (HFrEF) undergoing sacubitril/valsartan treatment were consecutively enrolled from 10 hospitals to serve as the derivation cohort. Another 1620 HFrEF patients receiving sacubitril/valsartan were included as the validation cohort. Worsening renal function (WRF) was defined as a serum creatinine increase of >0.3 mg/dL and/or >25 % at 8 months of sacubitril/valsartan treatment. The derivation cohort was used to identify independent predictive factors for WRF through multivariate analysis, which were then used to develop the risk score system. RESULTS: Among the 3125 HFrEF patients, 689 (22.0 %) patients had WRF at 8 months following sacubitril/valsartan treatment. In the derivation cohort, six prognostic factors (age, functional class, history of peripheral arterial disease, diabetes mellitus, gout or hyperuricemia, and serum albumin level) were independently associated with WRF, and were combined into a risk predicting score. This score showed accurate discrimination in the derivation and validation cohorts (Harrell's concordance indexes 0.74 and 0.71, 95 % confidence intervals 0.71-0.78 and 0.69-0.74, respectively). Patients with a higher risk score experienced a more rapid decline in renal function, poorer clinical outcomes, and a higher rate of discontinuation of sacubitril/valsartan treatment. CONCLUSIONS: This study developed a score for WRF after sacubitril/valsartan treatment, which may assist clinicians with risk stratification and therapeutic decision-making.

2023 Consensus of Taiwan Society of Cardiology on the Pharmacological Treatment of Chronic Heart Failure.

The prevalence of heart failure is increasing, causing a tremendous burden on health care systems around the world. Although mortality rate of heart failure has been significantly reduced by several effective agents in the past 3 decades, yet it remains high in observational studies. More recently, several new classes of drugs emerged with significant efficacy in reducing mortality and hospitalization in chronic heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). To integrate these effective therapies and prioritize them in the management of Asian patients, Taiwan Society of Cardiology has recently appointed a working group to formulate a consensus of pharmacological treatment in patients with chronic heart failure. Based on most updated information, this consensus provides rationales for prioritization, rapid sequencing, and in-hospital initiation of both foundational and additional therapies for patients with chronic heart failure.

2023 HRS/EHRA/APHRS/LAHRS Expert Consensus Statement on Practical Management of the Remote Device Clinic.

Remote monitoring is beneficial for the management of patients with cardiovascular implantable electronic devices by impacting morbidity and mortality. With increasing numbers of patients using remote monitoring, keeping up with higher volume of remote monitoring transmissions creates challenges for device clinic staff. This international multidisciplinary document is intended to guide cardiac electrophysiologists, allied professionals, and hospital administrators in managing remote monitoring clinics. This includes guidance for remote monitoring clinic staffing, appropriate clinic workflows, patient education, and alert management. This expert consensus statement also addresses other topics such as communication of transmission results, use of third-party resources, manufacturer responsibilities, and programming concerns. The goal is to provide evidence-based recommendations impacting all aspects of remote monitoring services. Gaps in current knowledge and guidance for future research directions are also identified.

Levosimendan attenuates electrical alternans and prevents ventricular arrhythmia during therapeutic hypothermia in isolated rabbit hearts.

BACKGROUND: Therapeutic hypothermia (TH) increases the susceptibility to ventricular arrhythmias (VAs) by prolonging action potential duration (APD) and facilitating arrhythmogenic spatially discordant alternans (SDA). Levosimendan, a calcium sensitizer, has been reported to shorten APD by enhancing the adenosine triphosphate (ATP)-sensitive K current. OBJECTIVE: The purpose of this study was to test the hypothesis that, during TH, levosimendan shortens the already prolonged APD, attenuates SDA, and prevents VA. METHODS: Langendorff-perfused isolated rabbit hearts were subjected to TH (30°C) for 15 minutes, followed by treatment with either levosimendan 0.5 µM (n = 9) or vehicle (n = 8) for an additional 30 minutes under TH. Using an optical mapping system, epicardial APD was evaluated by S1 pacing. SDA threshold was defined as the longest pacing cycle length (PCL) that induces the phenomenon of SDA. Ventricular fibrillation (VF) inducibility was evaluated by burst pacing for 30 seconds at the shortest PCL that achieved 1:1 ventricular capture. RESULTS: During TH, levosimendan shortened ventricular APD (PCL 400 ms; from 259 ± 8 ms to 241 ± 18 ms; P = .036) and decreased SDA threshold (from 327 ± 88 ms to 311 ± 68 ms; P = .011). VF inducibility was lowered from 39% ± 30% to 14% ± 12% with levosimendan (P = .018), whereas APD at PCL 400 ms (P = .161), SDA threshold (P = 1), and VF inducibility (P = .173) were not changed by vehicle. CONCLUSION: During TH, levosimendan could protect hearts against VA by shortening APD and decreasing SDA threshold. Enhancing ATP-sensitive K current with levosimendan might be a novel approach to preventing VA during TH.

Real-World Experience of Angiotensin Receptor-Neprilysin Inhibition in Reduced Ejection Fraction Heart Failure Patients With Advanced Kidney Disease.

OBJECTIVE: To investigate the effectiveness and safety of angiotensin receptor-neprilysin inhibitors (ARNIs) in real-world patients with heart failure with reduced ejection fraction (HFrEF) and advanced chronic kidney disease (estimated glomerular filtration rate [eGFR] < 30 mL/min per 1.73 m2), which have been excluded from the landmark trials. PATIENTS AND METHODS: This study examined 3281 patients pooled from two multicenter HFrEF cohorts, and 661 patients with baseline eGFR less than 30 mL/min per 1.73 m2 were further analyzed (the Taiwan Society of Cardiology - Heart Failure with reduced Ejection Fraction (TSOC-HFrEF) registry: May 1, 2013 to October 31, 2014, and the Treatment with Angiotensin Receptor neprilysin inhibitor fOr Taiwan Heart Failure patients (TAROT-HF) study: March 1, 2017, to December 31, 2018). Propensity score matching was performed to adjust for confounders. At 1-year follow-up, all-cause mortality, total heart failure hospitalizations, renal function, and left ventricular ejection fraction (LVEF) were used as the endpoints. RESULTS: After propensity score matching, 510 patients (age, 69.8±13.9 years; male, 61.0%; mean LVEF, 29.8±7.3%; mean eGFR, 19.8±9.0 mL/min per 1.73 m2) were included in the final analysis, including 278 patients receiving ARNI treatment (ARNI group) and 232 patients not on ARNI treatment (non-ARNI group). Baseline characteristics were comparable between the two groups. At 1 year, eGFR and LVEF measurements were significantly higher in the ARNI group than in the non-ARNI group (25.0±17.1 mL/min per 1.73 m2 vs 21.4±17.5 mL/min per 1.73 m2; P=.04; and 40.1±12.9% vs. 33.1±10.8%, P<.001, respectively). The ARNI group had significantly lower risks of 1-year all-cause mortality (19.4 vs 30.9 per 100-person year; P=.02), and total HF rehospitalizations (70.0 vs 110.4 per 100-person year; P=.01) than non-ARNI users. CONCLUSION: Our results show the effectiveness of ARNIs in HFrEF patients with advanced chronic kidney disease in a real-world setting.

Clinical significance of structural remodeling concerning substrate characteristics and outcomes in arrhythmogenic right ventricular cardiomyopathy.

Background: The substrate and ablation outcome in arrhythmogenic right ventricular cardiomyopathy (ARVC) with or without right ventricular (RV) dysfunction is unclear. Objective: We aimed to investigate ablation outcome and substrate in ARVC patients with or without RV dysfunction. Methods: We retrospectively studied ARVC patients with (group 1) or without RV dysfunction (group 2) undergoing substrate mapping/ablation. Baseline characteristics and electrophysiological features were compared. The RV was divided into 7 prespecified segments. The scarred segment was defined as more than 50% of the area with bipolar scar. A multivariate regression analysis was performed to predict the risk of ventricular tachycardia (VT) recurrence. Results: A total of 106 patients were enrolled (57 in group 1 and 49 in group 2). There were more men (73.7% vs 32.7%, P < .05) in group 1 than group 2. Group 1 patients demonstrated larger abnormal substrate in both the endocardium (13.4 ± 14.7 cm2 vs 7.8 ± 5.4 cm2, P = .014) and in the epicardium (40.3 ± 27.7 cm2 vs 14.2 ± 12.6 cm2, P = .002) and had more scar in the inferior portion/tricuspid valve (TV) than group 2 patients. Twenty-five patients had recurrences of VT/ventricular fibrillation. After multivariate analysis, the presence of a superior TV scar in the endocardium predicted the recurrence in patients with sustained VT. Conclusion: The presence of RV dysfunction was associated with a larger abnormal substrate in the endocardium and epicardium of the RV. A scar involving the inferior portion and TV is associated with RV dysfunction. Scarring in the superior TV of the endocardium can predict recurrence despite catheter ablation.

Utility of PREDICT-HF score in high-risk Asian heart failure patients receiving sacubitril/valsartan.

Objective: The aim of this study was to investigate the application of sacubitril/valsartan in clinical practice and the utility of PREDICT-HF score for outcome prediction in Asian heart failure patients with difference risk profiles. Methods: The TAROT-HF study was a multicenter, single-arm, observational study. Totally 1,187 outpatients with HFrEF treated with sacubitril/valsartan were enrolled and categorized by: (1) high-risk group with ≥1 of the following three risk factors: old age (≥80 years), low baseline systolic blood pressure (<100 mmHg), and renal impairment (eGFR <30 ml/min/1.73 m2), and (2) standard-risk group, those who did not have any risk factors. Clinical outcomes were assessed using the PREDICT-HF risk model. Results: A total of 305 (25.7%) patients matched the criteria for the high-risk group. The event rates of cardiovascular death or first unplanned heart failure hospitalization (HFH) among the overall population, high-risk, and standard-risk groups were 13.7, 24.9, and 10.8 events per 100 patient-years, respectively. The C statistics for the PREDICT-HF model in the overall cohort and high-risk group for cardiovascular death or first unplanned HFH at 2 years were 0.73 (95% CI 0.70-0.76) and 0.71 (95% CI 0.65-0.76), respectively. The permanent discontinuation rate among the high-risk patients was significantly higher than that among the standard-risk patients (8.3 vs. 2.5 per 100 patient-years, p < 0.001). Conclusions: Real-world outcomes of the TAROT-HF study demonstrated that the PREDICT-HF model performed well in Asian HFrEF patients. Three easily detected clinical profiles of age, renal function, and systolic BP could help to identify patients at risk before initiating sacubitril/valsartan.

[The destructive role of soluble Robo4 secreted by the M1-polarized-microglia during cerebral ischemia-reperfusion in blood-brain barrier integrity].

This project was aimed to investigate the role and the underlying mechanism of microglia polarization on blood-brain barrier (BBB) during cerebral ischemia-reperfusion. After construction of the mouse model of cerebral ischemia-reperfusion, upregulated IL-6 and TNF-α in peripheral blood and increased IL-6 and iNOS in ischemia tissues were confirmed. The supernatant expression of TNF-α and IL-6, as well as IL-6, iNOS and CD86 mRNA, was significantly increased in the of Bv-2 cells after oxygen-glucose deprivation/reoxygenation (OGD/R) model was constructed in vitro. For further understanding the expression pattern of RNAs, the next-generation RNA sequencing was performed and upregulation of Robo4 (roundabout guidance receptor 4) was found both in M1-polarized and OGD/R treated Bv-2 cells, which was also confirmed by RT-qPCR. Extracellular soluble Robo4 (sRobo4) protein also increased in the supernatant of M1-polarized and OGD/R treated Bv-2 cells. Treating bEND3 cells with the Robo4 recombinant protein, M1-polarized Bv-2 cell supernatant or OGD/R Bv-2 cell supernatant decreased trans-endothelial electrical resistance (TEER), suggesting the injury of BBB. In addition, Robo4 was also highly expressed in the serum of patients who experienced acute ischemia stroke and mechanical thrombectomy operation. All the results suggest that increased secretion of Robo4 by M1-polarized-microglia during cerebral ischemia-reperfusion is most likely one of the causes of BBB injury, and Robo4 may be one of the therapeutic targets for BBB functional protection.

Clinical impacts of sacubitril/valsartan on patients eligible for cardiac resynchronization therapy.

AIMS: Sacubitril/valsartan (SAC/VAL) has been used in patients with heart failure and reduced ejection fraction (HFrEF), and cardiac resynchronization therapy (CRT) could benefit the HFrEF patients with wide QRS durations. This study aimed to evaluate the clinical impacts of SAC/VAL on reverse cardiac remodelling in CRT-eligible and CRT-ineligible HFrEF patients with different QRS durations. METHODS AND RESULTS: The TAROT-HF study was a multicentre, observational study enrolling patients who initiated SAC/VAL from 10 hospitals since 2017. Patients with baseline left ventricular ejection fraction (LVEF) ≤ 35% were classified into two groups: (i) Group 1: CRT-eligible group, patients with left bundle branch block (LBBB) morphology plus QRS duration ≥130 ms or non-LBBB morphology plus QRS duration ≥150 ms; and (ii) Group 2: CRT-ineligible group. Propensity score matching was performed to adjust for confounders, and 1168 patients were analysed. Baseline characteristics were comparable between the two groups. The improvements in LVEF and left ventricular end-systolic volume index (LVESVi) were more significant in Group 2 than in Group 1 after 1 year SAC/VAL treatment (LVEF: 8.4% ± 11.3% vs. 4.5% ± 8.1%, P < 0.001; change percentages in LVESVi: -14.4% ± 25.9% vs. -9.6% ± 23.1%, P = 0.004). LVEF improving to ≥50% in Groups 1 and 2 constituted 5.2% and 20.2% after 1 year SAC/VAL treatment (P < 0.001). Multivariate analyses showed that wide QRS durations were negatively associated with the reverse cardiac remodelling in these HFrEF patients with SAC/VAL treatment. CONCLUSION: Despite SAC/VAL treatment, wide QRS durations are associated with lower degrees of left ventricular improvement than narrow ones in the HFrEF patients. Optimal intervention timing for the CRT-eligible patients requires further investigation.

Effects of Ivabradine on Patients with Depressed Left Ventricular Function after Cardiac Resynchronization Therapy.

Background: The potential synergistic effect of ivabradine and cardiac resynchronization therapy (CRT) in heart failure (HF) patients has rarely been studied. We aimed to evaluate the clinical benefits of ivabradine in patients with left ventricular dysfunction following CRT implantation. Methods: Two hundred and thirty-one patients receiving CRT were consecutively enrolled between January 2014 and December 2018 from two HF centers. A total of 123 patients had left ventricular ejection fraction (LVEF) < 40% and resting sinus heart rate (HR) ≥ 75 bpm after six months of CRT implantation. Among these patients, 45 were treated with ivabradine (Group 1), and 78 did not receive ivabradine treatment (Group 2). Results: Baseline characteristics and prescription rates of HF medications other than ivabradine were similar between the two groups. In Group 1, the mean HR decreased from 82.2 ± 11.4 bpm to 76.3 ± 10.5 bpm (p = 0.012), and the mean LVEF increased from 29.9 ± 6.5% to 38.8 ± 12.4% (p < 0.001). Atrial pacing percentage, biventricular pacing percentage, and burden of atrial fibrillation (AF) were not significantly different between the two groups during the study period. The patients' daily physical activity increased significantly in Group 1 compared to Group 2 (Δ daily activity 0.4 ± 0.7 hours/day vs. -0.1 ± 7.2 hours/day, p < 0.001). Conclusions: Ivabradine could effectively reduce HR and improve physical activity. It was safe to use and did not increase AF burden or affect biventricular pacing percentage in CRT recipients.

Effectiveness of home-based telerehabilitation programs on functional capacity and cardiac function in elderly heart failure patients: A prospective longitudinal study.

Decreased functional capacity and reduced cardiac function were the main symptoms in patients with heart failure (HF) and the incidence increases with advanced age. The guidelines recommend that exercise training should be considered for medically stable HF outpatients. Studies have confirmed that exercise can improve functional capacity, prognosis, and reduced hospitalization rates; however, very few studies have investigated the elderly. It is not clear whether exercise could be feasible in elderly HF. The aim of this study was to evaluate the effect of the 6-month heart failure post-acute care program focused on home-based cardiac telerehabilitation (HCTR) on functional capacity, cardiac function, and readmission rates in HF patients. A prospective longitudinal study was conducted. Study duration was from January 2018 to December 2019. HF patients with a left ventricular ejection fraction <40% and age ≧65 years were included and divided into intervention (n = 40) and control group (n = 41). We arranged a 6-month heart failure post-acute care program that included outpatient cardiac rehabilitation and home exercise for the intervention group. The response to home exercise was followed by telemonitor. The exercise parameters were recorded on the HF health management mobile application system platform by each patient and daily transmission to hospital's cloud database as HCTR, usual care program for the control group. Information such as general data, laboratory data, six-minute walk test, cardiac function, and admission record was collected from all patients. Eighty one patients between the ages of 65 and 92 completed the study. The mean age was 73.3 ± 5.0 and 75.6 ± 6.0 years in control and intervention group, respectively. The intervention group showed a statistically significant improvement in functional capacity, percentage change in the of six-minute walk distance (51.2% vs 17.7%, P < .05, 95% confidence interval -45.9 to -6.3). Left ventricular ejection fraction increased by 7.7%, which corresponds to 25.6% in relative terms (P < .05, 95% confidence interval -7.8 to -0.5). The readmission rate was 4.6% in the intervention group. Six months of post-acute HF focused on HCTR programs was safe, improved functional capacity, cardiac function, and decreased readmission rate in elderly patients with HF patients.

Efficacy of Cryoballoon Ablation for Atrial Fibrillation and Recurrence Predictors in an Asian Cohort.

BACKGROUND: Cryoballoon ablation (CBA) for atrial fibrillation (AF) is a rhythm control procedure used in clinical trials, mostly in Western countries. Its efficacy and the predictors of AF recurrence after CBA remain unclear for Asian populations. We aimed to investigate the efficacy of CBA and the predictors of AF recurrence after CBA in Asian AF patients. METHODS: We included consecutive AF patients undergoing CBA for rhythm control between 2014 and 2020. The baseline characteristics, including AF types, symptom severity, and left atrial diameter (LAD), were analyzed. Holter's monitoring and 12-lead ECG were performed to document AF recurrence. A multivariate Cox hazards regression model was used to evaluate the risk of AF recurrence. RESULTS: A total of 120 AF patients (aged 61.9 ± 9.3 years) were included. The percentage of patients free from AF in the year following CBA was 74.2%. Among the three independent predictors of AF recurrence within one year were the presence of persistent AF (p = 0.025), an LAD ≥ 4.75 cm (p = 0.016), and pre-procedural cardioversion (p = 0.025). All patients survived and none had a stroke after CBA. CONCLUSION: CBA for AF is an effective and safe procedure in Asian populations. The presence of persistent AF, an LAD ≥ 4.75 cm, and severe symptoms are predictors of AF recurrence in the year following CBA.

Rhythm Control Better Prevents Dementia than Rate Control Strategies in Patients with Atrial Fibrillation-A Nationwide Cohort Study.

Background: Atrial fibrillation (AF) increases the risk of dementia. Whether the pharmacological rhythm control of AF can reduce the risk of dementia compared to the rate control strategy remains unclear. We hypothesize that the rhythm control strategy is better than the rate control strategy in preventing dementia. Methods: AF patients aged ≥65 years were identified from the Taiwan National Health Insurance Database. Patients receiving anti-arrhythmic drugs at a cumulative defined daily dose (cDDD) of >30 within the first year of enrollment constituted the rhythm control group. Patients who used rate control medications for a cDDD of >30 constituted the rate control group. A multivariate Cox hazards regression model was used to determine the hazard ratio (HR) for dementia. Results: A total of 3382 AF patients (698 in the rhythm control group; 2684 in the rate control group) were analyzed. During a 4.86 ± 3.38 year follow-up period, 414 dementia events occurred. The rhythm control group had a lower rate of dementia than the rate control group (adjust HR: 0.75, p = 0.031). The rhythm control strategy reduced the risk of dementia particularly in those receiving aspirin (p = 0.03). Conclusions: In patients with AF, pharmacological rhythm control was associated with a lower risk of dementia than rate control over a long-term follow-up period, particularly in patients receiving aspirin treatment.

Transcription factor Klf9 controls bile acid reabsorption and enterohepatic circulation in mice via promoting intestinal Asbt expression.

Bile acid (BA) homeostasis is regulated by the extensive cross-talk between liver and intestine. Many bile-acid-activated signaling pathways have become attractive therapeutic targets for the treatment of metabolic disorders. In this study we investigated the regulatory mechanisms of BA in the intestine. We showed that the BA levels in the gallbladder and faeces were significantly increased, whereas serum BA levels decreased in systemic Krüppel-like factor 9 (Klf9) deficiency (Klf9-/-) mice. These phenotypes were also observed in the intestine-specific Klf9-deleted (Klf9vil-/-) mice. In contrast, BA levels in the gallbladder and faeces were reduced, whereas BA levels in the serum were increased in intestinal Klf9 transgenic (Klf9Rosa26+/+) mice. By using a combination of biochemical, molecular and functional assays, we revealed that Klf9 promoted the expression of apical sodium-dependent bile acid transporter (Asbt) in the terminal ileum to enhance BA absorption in the intestine. Reabsorbed BA affected liver BA synthetic enzymes by regulating Fgf15 expression. This study has identified a previously neglected transcriptional pathway that regulates BA homeostasis.

Antiviral therapy improves postoperative survival of patients with HBV-related hepatocellular carcinoma.

BACKGROUND: We aimed to investigate whether improvements in the prognosis of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) who have undergone hepatectomy are associated with reductions in the liver inflammation and fibrosis by antiviral therapy (AVT). METHODS: Patients who underwent hepatectomy and re-hepatectomy for HBV-related HCC between 2010 and 2019 were divided into two groups. Histological changes in liver were compared between initial and recurrence stages within each group. Propensity score matching (PSM) analysis was performed to compare prognostic outcomes. RESULTS: After PSM, AVT group showed a significantly better prognosis than did non-AVT group (RFS: 19.1% vs. 5.8%, P = 0.001; OS: 64.0% vs. 43.2%, P < 0.001). The improvements in G and S were independent protective factors for RFS (G: P < 0.001; S: P < 0.001) and OS (G: P = 0.013; S: P < 0.001). CONCLUSIONS: The application of AVT after initial surgery improved liver inflammation and fibrosis, further benefiting long-term outcomes of patients with HBV-related HCC.

Clinical impacts of scar reduction on gated myocardial perfusion SPECT after cardiac resynchronization therapy.

BACKGROUND: It had not been reported that myocardial scar shown on gated myocardial perfusion SPECT (GMPS) might reduce after cardiac resynchronization therapy (CRT). In this study, we aim to investigate the clinical impact and characteristic of scar reduction (SR) after CRT. METHODS AND RESULTS: Sixty-one heart failure patients following standard indication for CRT received twice GMPS as pre- and post-CRT evaluations. The patients with an absolute reduction of scar ≥ 10% after CRT were classified as the SR group while the rest were classified as the non-SR group. The SR group (N = 22, 36%) showed more improvement on LV function (∆LVEF: 18.1 ± 12.4 vs 9.4 ± 9.9 %, P = 0.007, ∆ESV: - 91.6 ± 52.6 vs - 38.1 ± 46.5 mL, P < 0.001) and dyssynchrony (ΔPSD: - 26.19 ± 18.42 vs - 5.8 ± 23.0°, P < 0.001, Δ BW: - 128.7 ± 82.8 vs - 25.2 ± 109.0°, P < 0.001) than non-SR group (N = 39, 64%). Multivariate logistic regression analysis showed baseline QRSd (95% CI 1.019-1.100, P = 0.006) and pre-CRT Reduced Wall Thickening (RWT) (95% CI 1.016-1.173, P = 0.028) were independent predictors for the development of SR. CONCLUSION: More than one third of patients showed SR after CRT who had more post-CRT improvement on LV function and dyssynchrony than those without SR. Wider QRSd and higher RWT before CRT were related to the development of SR after CRT.

DNA barcoding of Scomberomorus (Scombridae, Actinopterygii) reveals cryptic diversity and misidentifications.

The genus Scomberomorus is economically important; however, the taxonomic status and phylogenetic relationships in this genus are not clearly resolved, making it difficult to effectively protect and exploit fish resources. To clarify the taxonomic status of Scomberomorus species, mitochondrial cytochrome c oxidase I (COI) gene sequences of 150 samples were analyzed. The average genetic distance among 14 species was approximately 11 times greater than the distances within species, in accordance with the '10× rule' of species identification. Five of the 14 species did not form monophyletic clades based on a Bayesian inference gene tree. The application of four DNA-based species delimitation methods (automatic barcode gap discovery, barcode index numbers, Poisson tree process, and the K/θ method) yielded several key results. (1) Cryptic species were detected within Scomberomoruscommerson. (2) A Scomberomorusqueenslandicus sample from Australia was misidentified as S.commerson in the Barcode of Life Data System (BOLD). (3) Specimens originally identified as Scomberomorusguttatus was differentiated into four OTUs or species, two in the Yellow, South China, and Java seas, and two in geographically distant areas, one each in the Arabian Sea and the Bay of Bengal. (4) Six specimens from South Africa originally identified as S.plurilineatus most likely do not belong to the species. (5) Specimens identified as S.maculatus and S.regalis were conspecific; however, introgression cannot be ruled out. Our findings revealed cryptic diversity and difficulties in morphological identification of species in the genus Scomberomorus. This study provides scientifically based support for the conservation of germplasm resources of the genus Scomberomorus.