[Shenfu Injection regulates macrophage polarization via TLR4/NF-κB pathway to reduce inflammation in chronic heart failure].

This study aimed to investigate the therapeutic effect of Shenfu Injection on mice with chronic heart failure(CHF) and its effect on macrophage polarization. C57BL/6J mice were randomly assigned to the normal and model groups. The CHF model was established by intraperitoneal injection of isoproterenol(ISO, 7.5 mg·kg~(-1), 28 d). The successful modeling was determined by asses-sing the cardiac function and N-terminal pro-brain natriuretic peptide(NT-proBNP). The modeled mice were randomly divided into the model group, Shenfu Injection group, and TAK-242 group, and were injected intraperitoneally with the corresponding drugs for 15 days. Cardiac function was evaluated using echocardiography. Hematoxylin-eosin(HE) staining was used to detect the pathomorphology. Enzyme-linked immunosorbent assay(ELISA) was used to detect the values of serum NT-proBNP, interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), IL-10, and arginase 1(Arg-1). Flow cytometry was applied to detect the relative content and M1/M2 polarization of cardiac macrophages. Quantitative polymerase chain reaction(qPCR) and Western blot were used to detect the changes in the Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB) pathway-related mRNA and protein expressions. Compared with the normal group, mice in the model group had lower values of left ventricular ejection fraction(LVEF) and left ventricular fractional shorte-ning(LVFS), higher values of left ventricular internal diastolic end-diastolic(LVIDd), left ventricular internal diastolic end-systolic(LVIDs), NT-proBNP, TNF-α, and IL-6(P<0.01); the number of macrophages increased in cardiac tissues(P<0.05), and the values of M1-F4/80~+CD86~+ were increased(P<0.01), while the values of M2-F4/80~+CD163~+ decreased(P<0.05); the mRNA and protein expressions of TLR4, myeloid differentiation factor 88(MyD88), IκB kinase α(IKKα), and NF-κB p65 in myocardial tissues were significantly elevated(P<0.05, P<0.01). Compared with the model group, mice in the Shenfu Injection and TAK-242 groups showed elevated LVEF, LVFS, IL-10, and Arg-1 levels, and decreased LVIDd, LVIDs, NT-proBNP, TNF-α, and IL-6 levels(P<0.05, P<0.01); the cardiac F4/80~+CD11b~+(macrophage) and M1-F4/80~+ CD86~+ values were significantly down-regulated, while M2-F4/80~+CD163~+ values were increased(P<0.05, P<0.01); and the mRNA and protein expressions of TLR4, MyD88, IKKα, and NF-κB p65 in myocardial tissues were notably decreased(P<0.05, P<0.01). CHF mice have an imbalance of M1/M2 macrophage polarization, with M1-type macrophages predominating. Shenfu Injection promotes macrophage polarization towards M2, inhibits M1-type macrophage activation, and attenuates inflammatory responses in heart failure by regulating the TLR4/NF-κB signaling pathway.

Causal relationship from heart failure to kidney function and CKD: A bidirectional two-sample mendelian randomization study.

BACKGROUND: Heart Failure (HF) is a widespread condition that affects millions of people, and it is caused by issues with the heart and blood vessels. Even though we know hypertension, coronary artery disease, obesity, diabetes, and genetics can increase the risk of HF and Chronic Kidney Disease (CKD), the exact cause of these conditions remains a mystery. To bridge this gap, we adopted Mendelian Randomization (MR), which relies on genetic variants as proxies. METHODS: We used data from European populations for our Bidirectional Two-Sample MR Study, which included 930,014 controls and 47,309 cases of HF from the HERMES consortium, as well as 736,396 controls and 51,256 cases of CKD. We also employed several MR variations, including MR-Egger, Inverse Variance Weighted (IVW), and Weighted Median Estimator (WME), to guarantee the results were accurate and comprehensive.). RESULTS: In this study, the MR analysis found that individuals with a genetic predisposition for HF have an elevated risk of CKD. Our study revealed a significant association between the genetic prediction of HF and the risk of CKD, as evidenced by the IVW method [with an odds ratio (OR) of 1.12 (95% CI, 1.03-1.21), p = 0.009] and the WME [with an OR of 1.14 (95% CI, 1.03-1.26), p = 0.008]. This causal relationship remained robust even after conducting MR analysis while adjusting for the effects of diabetes and hypertension, yielding ORs of 1.13 (IVW:95% CI, 1.03-1.23), 1.12 (MR-Egger: 95% CI, 0.85-1.48), and 1.15 (WME:95% CI, 1.04-1.27) (p = 0.008). However, in the reverse analysis aiming to explore CKD and renal function as exposures and HF as the outcome, we did not observe a statistically significant causal link between CKD and HF. CONCLUSION: Our study demonstrates the significance of HF in CKD progression, thus having meaningful implications for treatment and the potential for discovering new therapies. To better understand the relationship between HF and CKD, we need to conduct research in a variety of populations.

Mapping clinical journeys of Asian patients presenting to the Emergency Department with syncope: Strict adoption of international guidelines does not reduce hospitalisations.

BACKGROUND: Limited data exists about management of syncope in Asia. The American College of Emergency Physicians (ACEP) and European Society of Cardiology (ESC) guidelines have defined the high-risk syncope patient. This study aims to determine the effectiveness of managing syncope in an Asian healthcare system and whether strict adherence of international guidelines would reduce hospitalizations. METHODS: Patients attending the Emergency Department of a Singaporean tertiary hospital with syncope were identified. Clinical journeys of all patients were meticulously mapped by interrogation of a comprehensive electronic medical record system and linkages with national datasets. Primary endpoint was hospitalization. Secondary endpoints were recurrent syncope within 1year and all-cause mortality. Expected admission rates based on application of ACEP/ESC guidelines were calculated. RESULTS: 638 patients (43.8±22.4years, 49.0% male) presented with syncope. 48.9% were hospitalized for 2.9±3.2days. Yields of common investigations ranged from 0 to 11.5% and no diagnosis was reached in 51.5% of patients. Diuretics use (HR 5.1, p=0.01) and prior hospitalization for syncope (HR 6.9, p<0.01) predicted recurrent syncope. Over 2.8 SD 0.3years of follow-up, 40 deaths occurred. 24 patients who died within 12months of presentation were admitted or had a firm diagnosis upon discharge. Application of guidelines did not significantly reduce hospitalisations, with limited agreement which patients warrant admission. (Actual 376, ACEP 354, ESC 391 admissions, p=NS). CONCLUSIONS: Unstructured management of syncope results in nearly half of patients being admitted and substantial healthcare expenditures, yet with limited diagnostic yield. Strict adoption of ACEP or ESC guidelines does not reduce admissions.

[The value of spleen sub-pedicle two steps severance with LigaSure in laparoscopic splenectomy].

OBJECTIVE: To evaluate the safety and utility of the methods of spleen sub-pedicle two steps severance with LigaSure Vessel Sealing System combined with ultrasound scalpel to resect peri-splenic ligaments during laparoscopic splenectomy. METHODS: The methods and the curative effect of 32 patients with laparoscopic splenectomy performed by the way as mentioned above were summarized and analyzed. 4 males, 28 females, median 36 years (range 16 - 64 years). Mean dimensions of spleens were 17 cm (range 11 - 23 cm). Nineteen patients had idiopathic thrombocytopenia purpura (ITP), 6 hereditary spherocytosis (HS) (5 of them were the same family constellation), 3 hemolytic anemia (HA), 2 spleen injury with haematoma infection, 1 Evan syndrome, 1 leukemia. Peri-splenic ligaments were resected by LigaSure combined with ultrasound scalpel, splenic pedicle was resected by spleen sub-pedicle two steps severance with LigaSure when splenic pedicle were sufficiently free. Splenic pedicle was non-excisional occluded by LigaSure at pancreatic cauda, in the first step and was occluded and resected alongside of the spleen in the second step. RESULTS: All of the 32 cases were completely succeed, the average operating time was 70 min (55 - 130 min), the estimated intraoperative blood loss was 200 ml (50 - 600 ml), no complications such as abdominal haemorrhage, visceral injury, pancreatic leakage and infection were observed. All the patients were healed well, the average hospital stay after an operation was 6 days. The average expense of each patients could save 8050 yuan because Endo-GIA was not used. CONCLUSIONS: Spleen sub-pedicle two steps severance with LigaSure Vessel Sealing System combined with ultrasound scalpel to resect peri-splenic ligaments during laparoscopic splenectomy, which shorten the operating persistence time with less hemorrhage is a safe, effective and low-cost minimally invasive surgery in selective cases.