Lipoprotein(a): Are we ready for large-scale clinical trials?

Cardiovascular diseases (CVD) are currently the most important disease threatening human health, which may be due to the high incidence of risk factors including hyperlipidemia. With the deepening of research on lipoprotein, lipoprotein (a) [Lp(a)] has been shown to be an independent risk factor for atherosclerotic cardiovascular diseases and calcified aortic valve stenosis and is now an unaddressed "residual risk" in current CVD management. Accurate measurement of Lp(a) concentration is the basis for diagnosis and treatment of high Lp(a). This review summarized the Lp(a) structure, discussed the current problems in clinical measurement of plasma Lp(a) concentration and the effects of existing lipid-lowering therapies on Lp(a).

Association between performance measures and clinical outcomes in patients with heart failure in China: Results from the HERO study.

BACKGROUND: There is great heterogeneity in the quality of care among hospitals in China, but studies on the performance measures and prognosis of patients with heart failure (HF) are still deficient. HYPOTHESIS: Performance measures have been used as a guideline to clinicans, however, the association between them and outcomes among HF patients in China remains unclear. METHODS: We analyzed 4497 patients with HF from the Heart Failure Registry of Patient Outcomes study. Performance measures were determined according to the guidelines, and the patients were divided into four groups based on a composite performance score. Multiple imputation and Cox proportional-hazard regression models were used to assess the association between the performance measures and clinical outcomes. RESULTS: Overall, only 12.5% of patients met the top 25% of the performance measures, whereas 33.5% of patients met the bottom 25% of the measures. A total of 992 (22.2%) patients died within 1 year, involving a larger proportion of patients who had met only the bottom 25% of the performance measures than had met the top 25% (27.0% vs. 16.3%, respectively). The patients who met the top 25% of the measures had a lower 1-year mortality rate (adjusted hazard ratio: 0.78, 95% confidence interval: 0.61-0.98). CONCLUSIONS: The association between performance measures and mortality appeared to follow a dose-response pattern with a larger degree of compliance with performance measures being associated with a lower mortality rate in patients with HF. Accordingly, the quality of care for patients with HF in China needs to be further improved.

Effect of Intensive Blood Pressure Control on Cardiovascular Outcomes in Cancer Survivors.

BACKGROUND: To evaluate whether cancer modifies the effect of intensive blood pressure control on major cardiovascular outcomes. METHODS: Using data of the SPRINT (Systolic Blood Pressure Intervention Trial), we compared the risk of the composite outcomes of myocardial infarction, other acute coronary syndromes, stroke, heart failure, and cardiovascular death in patients with and without a history of cancer. Using Cox proportional hazards regression, we tested interactions between history of cancer and intensive blood pressure control on major cardiovascular outcomes. RESULTS: The study included a total of 9336 patients, with a mean age of 67.9±9.4 years, among whom 2066 (22.2%) were cancer survivors. Over a median follow-up of 3.2 years, 561 primary cardiovascular outcomes were observed. Cancer survivors had a similar risk of experiencing the primary outcome compared with patients without cancer after multivariable adjustment (adjusted hazard ratio, 0.94 [95% CI, 0.77-1.15]). Intensive blood pressure control reduced risk of the primary cardiovascular outcome similarly for cancer survivors (hazard ratio, 0.70 [95% CI, 0.51-0.97]) and patients without cancer (HR, 0.76 [95% CI, 0.63-0.93]; P for interaction 0.74). CONCLUSIONS: In SPRINT study, intensive blood pressure treatment reduced the risk of major cardiovascular events in cancer survivors to a similar extent to that of patients without cancer. Cancer history not requiring active treatment in last 2 years should not be an obstacle to intensive treatment of hypertension. This post hoc analysis should be considered as hypothesis-generating and merit further clinical trial. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01206062.

Effect of SGLT2 inhibitors on cardiovascular events in patients with atrial fibrillation: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) is reported to reduce incident atrial fibrillation (AF) in patients with or without diabetes; however, its cardiovascular (CV) benefit for AF patients remains unclear. SS AIMS: To investigate the effect of SGLT2i on the incidence of CV events in patients with AF. METHODS: Six randomized controlled trials (RCTs) assessing the effects of SGLT2i on CV outcomes in patients with or without AF were included (PROSPERO: CRD 42023431535). The primary endpoint was the composite outcome of heart failure (HF) hospitalization and CV death. Additionally, we assessed the effects of treatment in prespecified subgroups on HF hospitalization, CV death, and all-cause mortality. RESULTS: Among 38,529 participants from all trials, 5018 patients with AF were treated with SGLT2i. The follow-up period of these trials ranged from 2.3 to 3.3 years. SGLT2i treatment was significantly associated with the risk reduction of primary endpoint in patients with AF (risk ratio [RR] 0.81, 95% confidence interval [CI] 0.74-0.88; p < 0.001), consistent with the finding in the general population (p for interaction = 0.76). SGLT2i was also associated with a consistent reduction in the risk of HF hospitalization in patients with AF (RR 0.76, 95% CI 0.69-0.84; p < 0.001) or not (RR 0.72, 95% CI 0.64-0.80; p < 0.0001), with no statistical difference between them (p for interaction = 0.41). Meta-regression further revealed no significant association between the prevalence of HF with reduced ejection fraction or diabetes and the effect size of SGLT2i. CONCLUSIONS: The treatment effects of SGLT2i were associated with a lower incidence of CV events, especially HF hospitalization, in patients with AF.

Body mass index, frailty, and outcomes in heart failure with preserved ejection fraction.

AIMS: Relationship between body mass index (BMI), frailty, and clinical adverse events remains unclear in patients with heart failure (HF) with preserved ejection fraction (HFpEF) in different patient populations. We aimed to compare the association of BMI, frailty, and clinical adverse events between a US cohort from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) study and a Chinese cohort from the Heart Failure Registry of Patient Outcomes (HERO) study. METHODS AND RESULTS: We used data of 1715 participants enrolled from America in the TOPCAT study and 1487 patients with HFpEF in the Chinese registry study, the HERO. We evaluated the relationship between BMI and frailty using multivariate restricted cubic spline logistic regression. Association between frailty and BMI categories and primary outcomes including HF hospitalization, aborted sudden death, and cardiovascular death, all-cause mortality, and HF hospitalization were analysed by Cox proportional hazards models. The patients' mean age was 72 ± 11 years for both study populations, with 50% and 46% female for the TOPCAT study and the HERO study, respectively. Patients in the TOPCAT study had a higher mean BMI (33.9 vs. 24 kg/m2), with 72.3% vs. 52.9% defined as moderately to severely frail (frailty index > 0.3). In the TOPCAT study, risk of frailty rose as BMI increased, but not in the HERO study. Patients with frailty were at significant higher risk for the primary composite outcomes [hazard ratio (HR) 1.84 (95% confidence interval: 1.46-2.32)], all-cause mortality [HR 1.73 (1.34-2.25)], and HF hospitalization [HR 1.83 (1.40-2.40)] in the TOPCAT study. The corresponding numbers in the HERO study were 1.26 (1.01-1.57), 2.21 (1.45-3.35), and 1.15 (0.81-1.37), respectively. The association of frailty with clinical outcomes did not vary with BMI categories in the two studies. CONCLUSIONS: BMI distribution and association between BMI and frailty risk were different between the two study populations. Frailty was associated with clinical adverse events and this association was consistent across different BMI categories in both studies.

Impact of Sodium-Glucose Cotransporter 2 Inhibitor on Recurrence After Catheter Ablation for Atrial Fibrillation in Patients With Diabetes: A Propensity-Score Matching Study and Meta-Analysis.

BACKGROUND: The association between sodium-glucose cotransporter 2 inhibitors (SGLT2i) and atrial fibrillation (AF) recurrence after catheter ablation among patients with diabetes and AF remains unclear. METHODS AND RESULTS: Patients with AF undergoing initial catheter ablation with a history of diabetes from the China AF registry were included. Patients using SGLT2i were identified and matched by propensity score with non-SGLT2i patients in a 1:3 ratio. The main outcome was AF recurrence during the 18-month follow-up. A total of 138 patients with diabetes with SGLT2i therapy and 387 without SGLT2i were analyzed. AF recurrence occurred in 37 patients (26.8%) in the SGLT2i group and 152 patients (39.3%) in the non-SGLT2i group during a total of 593.3 person-years follow-up. The SGLT2i group was associated with lower AF recurrence compared with the non-SGLT2i group (hazard ratio, 0.63 [95% CI, 0.44-0.90], P=0.007). A total of 4 studies were analyzed in our meta-analysis demonstrating that SGLT2i was associated with lower AF recurrence after catheter ablation (odds ratio, 0.61 [95% CI, 0.54-0.69]; P<0.001, I2=0.0%). CONCLUSIONS: Our prospective study coupled with a meta-analysis demonstrated a lower risk of AF recurrence with the use of SGLT2i among patients with diabetes after AF ablation.

Re-evaluating serum angiotensin-converting enzyme in sarcoidosis.

Sarcoidosis is a systemic inflammatory disease of unknown etiology, which mainly affects the lungs and lymph nodes, as well as extrapulmonary organs. Its incidence, and prevalence rate, and disease course largely vary with regions and populations globally. The clinical manifestations of sarcoidosis depend on the affected organs and the degree of severity, and the diagnosis is mainly based on serum biomarkers, radiographic, magnetic resonance, or positron emission tomography imaging, and pathological biopsy. Noncaseating granulomas composing T cells, macrophages, epithelioid cells, and giant cells, were observed in a pathological biopsy, which was the characteristic pathological manifestation of sarcoidosis. Angiotensin-converting enzyme (ACE) was first found in the renin-angiotensin-aldosterone system. Its main function is to convert angiotensin I (Ang I) into Ang II, which plays an important role in regulating blood pressure. Also, an ACE insertion/deletion polymorphism exists in the human genome, which is involved in the occurrence and development of many diseases, including hypertension, heart failure, and sarcoidosis. The serum ACE level, most commonly used as a biomarker in diagnosing sarcoidosis, in patients with sarcoidosis increases. because of epithelioid cells and giant cells of sarcoid granuloma expressing ACE. Thus, it serves as the most commonly used biomarker in the diagnosis of sarcoidosis and also aids in analyzing its therapeutic effect and prognosis in patients with sarcoidosis.

Recent progress of TP/NIR fluorescent probes for metal ions.

Metal ions are of significance in various pathological and physiological processes. As such, it is crucial to monitor their levels in organisms. Two-photon (TP) and near-infrared (NIR) fluorescence imaging has been utilized to monitor metal ions because of minimal background interference, deeper tissue depth penetration, lower tissue self-absorption, and reduced photodamage. In this review, we briefly summarize recent progress from 2020 to 2022 of TP/NIR organic fluorescent probes and inorganic sensors in the detection of metal ions. Additionally, we present an outlook for the development of TP/NIR probes for bio-imaging, diagnosis of diseases, imaging-guided therapy, and activatable phototherapy.

[Advances in methods for detecting plastics biodegradation].

The pollution caused by improper handling of plastics has become a global challenge. In addition to recycling plastics and using biodegradable plastics, an alternative solution is to seek efficient methods for degrading plastics. Among them, the methods of using biodegradable enzymes or microorganisms to treat plastics have attracted increasing attention because of its advantages of mild conditions and no secondary environmental pollution. Developing highly efficient depolymerizing microorganisms/enzymes is the core for plastics biodegradation. However, the current analysis and detection methods cannot meet the requirements for screening efficient plastics biodegraders. It is thus of great significance to develop rapid and accurate analysis methods for screening biodegraders and evaluating biodegradation efficiency. This review summarizes the recent application of various commonly used analytical techniques in plastics biodegradation, including high performance liquid chromatography, infrared spectroscopy, gel permeation chromatography, and determination of zone of clearance, with fluorescence analysis techniques highlighted. This review may facilitate standardizing the characterization and analysis of plastics biodegradation process and developing more efficient methods for screening plastics biodegraders.

A turn-on fluorescent probe based on ESIPT and AIEE mechanisms for the detection of butyrylcholinesterase activity in living cells and in non-alcoholic fatty liver of zebrafish.

Butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) are two important cholinesterase enzymes in human metabolism which are closely related to various diseases of the liver. BChE and AChE are difficult to be distinguished due to their similarity in biochemical properties. Therefore, developing BChE-specific probes with high sensitivity and low background reading is desirable for the relevant biological applications. Herein, we reported the design and synthesis of a fluorescent probe HBT-BChE for biological detection and imaging of BChE. The probe is triggered by BChE-mediated hydrolysis, releasing a fluorophore that holds AIEE and ESIPT properties with large Stokes shift (>100 nm), rendering the probe features of low background interference and high sensitivity. The probe can also distinguish BChE from AChE with a low detection limit of 7.540 × 10-4 U/mL. Further in vitro studies have shown the ability of HBT-BChE to detect intracellular BChE activity, as well as to evaluate the efficiency of the BChE inhibitor. More importantly, the in vivo studies of imaging the BChE activity level in liver tissues using zebrafish as the model animal demonstrated the potential of HBT-BChE as a powerful tool for non-alcoholic fatty liver disease.

Role of Toll-Like Receptors and Th Responses in Viral Myocarditis.

Myocarditis is the common cause of sudden cardiac death, dilated cardiomyopathy (DCM) and heart failure (HF) in young adults. The most common type of myocarditis is viral myocarditis (VMC). Toll-like receptors (TLRs) are vital to identify pathogens in vivo. TLRs promote the differentiation of naive CD4+T cells to T helper (Th) cells, activate the immune response, and participate in the pathogenesis of autoimmune and allergic diseases. Although the pathogenesis of VMC is unclear, autoimmune responses have been confirmed to play a significant role; hence, it could be inferred that VMC is closely related to TLRs and Th responses. Some drugs have been found to improve the prognosis of VMC by regulating the immune response through activated TLRs. In this review, we discuss the role of TLRs and Th responses in VMC.

Benzothiazole derivatives based colorimetric and fluorescent probes for detection of amine/ammonia and monitoring the decomposition of urea by urease.

Amines play critical roles in chemical, agrochemical and pharmaceutical industries. However, volatile amine vapours cause widespread pollution and threaten human health. An efficient, highly sensitive and recyclable sensor for monitoring amine vapours is highly demanded. Typically, 2-(2-hydroxy-5-methyl) benzothiazole (HBT) derivates exhibit excellent aggregation-induced emission (AIE) phenomena in keto form originated from a unique excited-state intramolecular proton transfer (ESIPT) process. In this work, we have designed and synthesized two HBT-based fluorescent probes for ratiometric detection toward amine vapours and ammonia. In addition, the detection limits for ammonia were calculated as 226 ppm and 13 ppm respectively. Additionally, the test strips and electrospinning film dopped with fluorescent probes were utilized to recognize amine vapours and ammonia colorimetric with high sensitivity in solid states. According to the above characteristics, probes could monitor the biological activity of urease conveniently and rapidly.

PEGylated Dimeric BODIPY Photosensitizers as Nanocarriers for Combined Chemotherapy and Cathepsin B-Activated Photodynamic Therapy in 3D Tumor Spheroids.

The development of enzyme-activatable photosensitizers and their combination with conventional chemodrugs for antitumor therapy are of great interest. In this work, we reported a strategy of constructing activatable photosensitizers by interfering with the intramolecular charge transfer (ICT) state of an orthogonal boron dipyrromethene (BODIPY) chromophore. By conjugating a cathepsin B substrate peptide with a photosensitizer, BDP-BDP-NH2, the reactive oxygen species (ROS) generation of the product (ABP) was significantly suppressed due to the blockage of the electron-donating amino group. In vitro experiments proved the recovery of ROS generation under laser irradiation after the peptide linker was cleaved by cathepsin B. The ABP was then PEGylated and modified with a cRGD peptide (RNC) to encapsulate a hydrophobic anticancer drug, 10-hydroxycamptothecin (HCPT). The formed RNC/HCPT nanoparticles had good stability in serum-containing solutions with a hydrodynamic size of around 200 nm. The combination of cathepsin B-activated PDT and chemotherapy exhibited a strong ability to inhibit the growth of 4T1 breast cancer cells while promoting the induction of cell apoptosis. The RNC/HCPT nanoparticles also showed the ability to penetrate the 4T1 three-dimensional (3D) tumor spheroids and effectively shrunk the size of the spheroids. Taken together, our strategy offers a platform for antitumor drug delivery with an activatable PDT effect and combined therapy.