Currently, brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are widely used as diagnostic biomarkers for heart failure (HF) and cardiac dysfunction in clinical medicine. They are also used as postmortem biomarkers reflecting cardiac function of the deceased before death in forensic medicine. Several previous studies have reviewed BNP and NT-proBNP in clinical medicine, however, few articles have reviewed their application in forensic medicine. The present article reviews the biological features, the research and application status, and the future research prospects of BNP and NT-proBNP in both clinical medicine and forensic medicine, thereby providing valuable assistance for clinicians and forensic pathologists.

Mn(III) ortho-N-alkyl- and N-alkoxyalkyl porphyrins (MnPs) were initially developed as superoxide dismutase (SOD) mimics. These compounds were later shown to react with numerous reactive species (such as ONOO-, H2O2, H2S, CO3•-, ascorbate, and GSH). Moreover, the ability of MnPs to oxidatively modify activities of numerous proteins has emerged as their major mechanism of action both in normal and in cancer cells. Among those proteins are transcription factors (NF-κB and Nrf2), mitogen-activated protein kinases, MAPKs, antiapoptotic bcl-2, and endogenous antioxidative defenses. The lead Mn porphyrins, namely, MnTE-2-PyP5+ (BMX-010, AEOL10113), MnTnBuOE-2-PyP5+ (BMX-001), and MnTnHex-2-PyP5+, were tested in numerous injuries of normal tissue and cellular and animal cancer models. The wealth of the data led to the progression of MnTnBuOE-2-PyP5+ into four Phase II clinical trials on glioma, head and neck cancer, anal cancer, and multiple brain metastases, while MnTE-2-PyP5+ is in Phase II clinical trial on atopic dermatitis and itch.

Biomarkers such as B-type natriuretic peptide (BNP), N-terminal pro-BNP (NT-proBNP), cardiac troponin (cTn), and CK-MB contribute significantly to the diagnosis of cardiovascular disease (CVD). Recent studies have demonstrated that suppression of tumorigenicity 2 (ST2) is associated with CVD, but a meta-analysis of ST2 levels in different CVDs has yet to be conducted. Therefore, the present study aimed to investigate soluble ST2 (sST2) levels in patients with ischemic heart disease (IHD), myocardial infarction (MI), and heart failure (HF). A total of 1,425 studies were searched across four databases, of which 16 studies were included in the meta-analysis. The Newcastle–Ottawa Quality Assessment Scale (NOS) values of all 16 studies were ≥7. The meta-analysis results indicated that the sST2 level was not correlated with IHD (standard mean difference [SMD] = 0.58, 95% confidence interval [95% CI] = 0.00 to 1.16, p = 0.05) or MI (weighted mean difference [WMD] = 0.17, 95% CI = −0.22 to 0.55, p = 0.40) but was significantly associated with HF (WMD = 0.21, 95% CI = 0.04 to 0.38, p = 0.02; I2 = 99%, p < 0.00001). sST2 levels did not differ significantly between patients with IHD or MI and healthy individuals; however, we believe that ST2 could be used as an auxiliary diagnostic biomarker of HF.

B cells constitute a major component of infiltrating immune cells in colorectal cancer (CRC). However, the characteristics of B cells and their clinical significance remain unclear. In this study, using single-cell RNA sequencing and multicolour immunofluorescence staining experiments, we identified five distinct subtypes of B cells with their marker genes, distribution patterns and functional properties in the CRC tumour microenvironment. Meanwhile, we found a higher proportion of IgG plasma cells in tumour sites than that in adjacent normal mucosal tissues. In addition, the CXCL13-producing CD8 + T cells in the tumour tissues could promote the formation of tertiary lymphoid structure (TLS) B cells, and the CCL28-CCR10 axis is pivotal for IgG plasma cell migration from the periphery of TLSs to the tumour stroma. Finally, we identified four distinct colon immune classes (CICs: A-D) and found that CD20 + B cells within TLSs were enriched in one immune-inflamed or hot tumour group (CIC D). This B cell-rich group, which was characterized by strong antigen presentation, IgG plasma cells accumulation, microsatellite instability-high (MSI-H) and high tumour mutation Abbreviations: CICs, colon immune classes; CO 2 , carbon dioxide; CRC, colorectal cancer; dMMR, DNA mismatch-repair-deficient; GEO, Gene Expression Omnibus; GSVA, gene set variation analysis; HPFs, high power fields; ICB, immune checkpoint blockade; LPS, lipopolysaccharide; MSI-H, microsatellite instability-high; SCENIC, single-cell regulatory network inference and clustering; ssGSEA, single sample gene set enrichment analysis; TCGA-COAD, the Cancer Genome Atlas Colon Adenocarcinoma; TLS, tertiary lymphoid structure; TMB-H, high tumour mutation burden; TME, tumour microenvironment. Jie Xia, Zhangjuan Xie and Gengming Niu contributed equally to this study.

The aim of the present study was to investigate the differential expression of B-type natriuretic peptide (BNP) between the left and right ventricle (RV) in sudden cardiac death (SCD). A total of 26 forensic autopsy cases of sudden death (survival time <30 min, postmortem interval <48 h or frozen within 6 h following death) in the present institute were examined. The cases consisted of acute ischemic heart disease (AIHD, n=15) with/without apparent myocardial necrosis as a sign of infarction (acute myocardial infarction, n=6; ischemic heart disease, IHD, n=9), and arrhythmogenic right ventricular cardiomyopathy (ARVC/D, n=5), in addition to traffic accidents and high falls without any pre existing heart disease as control (C, total n=6). BNP was investigated in all cases by the colloidal gold method, hematoxylin-eosin staining, immunohistochemistry (IHC) and the molecular pathological method. The IHC results demonstrated that a positive BNP immunostaining was detected in all groups; however, there was no difference between different causes of death. Pericardial N-terminal (NT)-proBNP concentration was significantly increased in deaths resulting from AIHD and ARVC/D compared with control group. The relative quantification of BNP mRNA demonstrated that relative expression levels of BNP mRNA were significantly increased in the left ventricle (LV) in the AIHD group, and in the RV of the ARVC/D group. The relative quantification difference and ratio of BNP mRNA between LV and RV demonstrated a significantly greater value in the AIHD group compared with control group. BNP mRNA in myocardium and NT-proBNP concentration in pericardial fluid were elevated in SCD patients, and left ventricular dysfunction predominated in AIHD patients, whereas right ventricular dysfunction predominated in ARVC/D patients. The results of the present study suggest the possible use of molecular pathology of BNP for the determination of terminal cardiac function in SCD and analysis of its fatal mechanism in forensic practice.