Towards understandings of serine/arginine-rich splicing factors

Serine/arginine-rich splicing factors (SRSFs) refer to twelve RNA-binding proteins which regulate splice site recognition and spliceosome assembly during precursor messenger RNA splicing. SRSFs also participate in other RNA metabolic events, such as transcription, translation and nonsense-mediated decay, during their shuttling between nucleus and cytoplasm, making them indispensable for genome diversity and cellular activity. Of note, aberrant SRSF expression and/or mutations elicit fallacies in gene splicing, leading to the generation of pathogenic gene and protein isoforms, which highlights the therapeutic potential of targeting SRSF to treat diseases. In this review, we updated current understanding of SRSF structures and functions in RNA metabolism. Next, we analyzed SRSF-induced aberrant gene expression and their pathogenic outcomes in cancers and non-tumor diseases. The development of some well-characterized SRSF inhibitors was discussed in detail. We hope this review will contribute to future studies of SRSF functions and drug development targeting SRSFs.

Deep learning in digital pathology image analysis: a survey / 医学前沿

Deep learning (DL) has achieved state-of-the-art performance in many digital pathology analysis tasks. Traditional methods usually require hand-crafted domain-specific features, and DL methods can learn representations without manually designed features. In terms of feature extraction, DL approaches are less labor intensive compared with conventional machine learning methods. In this paper, we comprehensively summarize recent DL-based image analysis studies in histopathology, including different tasks (e.g., classification, semantic segmentation, detection, and instance segmentation) and various applications (e.g., stain normalization, cell/gland/region structure analysis). DL methods can provide consistent and accurate outcomes. DL is a promising tool to assist pathologists in clinical diagnosis.

Expression changes of S100 family proteins and their functional significances in renal cancer / 中国药科大学学报

@#Renal cell carcinoma is a common type malignant tumor of the urinary system. The global incidence of renal cancer is 2. 2%. S100 proteins are involved in the regulations of proliferation, differentiation, apoptosis, and Ca2+ homeostasis, etc. S100 proteins are often closely associated with tumor progression. This review lists the expression changes of S100s and their functional significances in renal cancers, providing a new direction for the researches and treatments of renal cancer. The interpretation of S100 in the regulation of VHL/HIF signaling pathways should be a future direction.

Gastroenteropancreatic neuroendocrine neoplasms: concepts and related issues / 浙江大学学报·医学版

The incidence of neuroendocrine neoplasms (NENs) has been gradually increasing and most of NENs are located in gastroenteropancreatic system. With the application of target therapeutic drugs in recent years, the precise pathological diagnosis is required critically for effective clinical treatment: target therapy needs targeted pathological diagnosis. In this article, the definition of NENs, and the century-long evolution of diagnostic terms and grades are reviewed. The eight steps of pathological diagnosis of NENs for clinical needs are described. Four inconsistent concepts in NENs diagnosis are also discussed, that is immunohistochemical biomarkers of pathological diagnosis, subpopulation of neuroendocrine neoplasms with high proliferative activity, general adenocarcinomas with neuroendocrine differentiation and molecular genetics characteristics. To correctly understand these issues would be of great value for diagnosis and treatment of NENs.

Association of neuroendocrine differentiation with progression and prognosis of gastric adenocarcinoma / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the association of neuroendocrine differentiation with progression and prognosis of gastric adenocarcinoma.</p><p><b>METHODS</b>Clinicopathological data of 240 patients with gastric adenocarcinomas were retrospectively analyzed. The expression of chromogranin A, synaptophysin and secrectagogin in cancer tissue was assessed by immunohistochemistry. The association of neuoroendocrine differentiation parameters with disease progression and survival of patients was analyzed.</p><p><b>RESULTS</b>The expression of synaptophysin was positively correlated with depth of invasion and secretagogin more often expressed in cases with lymph node metastasis. In Lauren diffuse type of cancer, expression of chromogranin A and secretagogin was unfavorable prognostic predictor. In TNM stage II adenocarcinoma, expression of chromogranin A and synaptophysin related to poor survival, and multivariate Cox proportional hazard model showed that synaptophysin was an independent predictor for poor survival.</p><p><b>CONCLUSION</b>Neuroendocrine differentiation predicts deeper depth of invasion, more possibility of lymph node metastasis and poor survival in gastric adenocarcinoma.</p>

Update of pathological diagnosis of pulmonary neuroendocrine tumor / 浙江大学学报·医学版

Pulmonary neuroendocrine tumors are common in pathological practice and its pathological classification and histological grading are not exactly the same as that of those in the digestive tract and pancreas. In 2015 edition of World Health Organization classification, pulmonary neuroendocrine tumors are classified as carcinoid tumors (including typical carcinoid and atypical carcinoid), small cell lung carcinoma, large cell neuroendocrine carcinoma, and precursor lesion diffuse idiopathic neuroendocrine cell hyperplasia; each category has distinctive morphological and immunohistochemical features. The morphologic features including growth patterns and cytological appearances are keys for the diagnosis of neuroendocrine tumor, and immunohistochemical findings are also critical for its diagnosis. Furthermore, the diagnostic criteria vary for different types of specimen. In this article, we present a concise review and summary of the update of clinicopathological characterizations of pulmonary neuroendocrine tumor, with an emphasis on its diagnostic criteria and differential diagnosis.

Location and functions of secretagogin protein / 浙江大学学报·医学版

Secretagogin (SCGN) is a novel member of EF-hand Ca2+-binding proteins, which was identified in islet β cells by Wagner. SCGN is a six EF-hand Ca2+-binding protein, primarily expressed on the neuroendocrine axis and the central nervous system. The protein has abundant biological functions. A certain concentration of calcium ion can lead to conformation change of SCGN, resulting in the change of intracellular signal transduction. Preliminary studies showed that SCGN would be used to treat stress reaction, such as mental illness (depression), burns or post-traumatic stress disorder and chronic stress reaction caused by pain. In Alzheimer's disease, the expression of SCGN in the hippocampus can boycott neurodegeneration. In neuroendocrine tumors, SCGN presents a good consistency with neuroendocrine markers such as CgA, Syn, and NSE, with a higher overall sensitivity and specificity. In addition, SCGN is released into serum after neural damage in cerebral ischemic diseases, suggesting that SCGN can be used as a marker for brain trauma. In this article, we review the recent research progress of secretagogin, focus on its distribution and functions in various tumorous diseases and non-tumorous diseases, such as Alzheimer's disease.

Research progress on genome-wide association studies of colorectal cancer / 浙江大学学报·医学版

Colorectal cancer (CRC), one of the most common malignant tumors, is caused both by environmental and genetic factors. Genetic factor plays an important role in the pathogenesis of CRC. Genome-wide association study (GWAS) is a new tool of genetic research. A series of susceptibility genes and loci of the complex diseases has been identified with GWAS strategy. In this article, the research progress on GWAS of CRC is reviewed, and the advantages and limitations of GWAS study as well as the prospective of its application are discussed.

Reg IV, a differentially expressed gene in colorectal adenoma / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To discover and identify differentially expressed genes associated with colorectal adenoma formation and the role of RegIV in colorectal adenoma differentiation.</p><p><b>METHODS</b>A subtracted cDNA library was constructed with cDNAs that were isolated from either the normal mucosa or adenoma tissue of a single patient. Suppressive subtractive hybridization (SSH) combined with virtual northern blotting was used to characterize differentially expressed genes and contigs were assembled by electronic cloning (in silico cloning) with the EST database. Semi-quantitative RT-PCR was performed in 9 colorectal adenomas.</p><p><b>RESULTS</b>The amino acid sequence was determined with open reading frame (ORF) prediction software and was found to be 100% homologous to the protein product of RegIV (a novel gene isolated from a large inflammatory bowel disease library). RegIV was found to be highly expressed in all of the adenoma samples (9/9) compared with the normal mucosa samples, while 5/6 cases showed RegIV to be more strongly expressed in adenocarcinoma.</p><p><b>CONCLUSION</b>RegIV may play an important role in the initiation of colorectal adenoma differentiation, and its detection may be useful in the early diagnosis of colorectal adenoma formation.</p>

Research progress in guanylin family / 中国病理生理杂志

Guanylin family, described in recent 10 years, is a series of small peptides (including guanylin, uroguanylin and lymphoguanylin) with structural and functional similarities to heat-stable enterotoxins (STs) elaborated by various pathogenic bacteria. They are abundance of cysteines and are endogenous activators of guanylyl cyclase-C (GC-C) receptors. Immunoreactive guanylin family peptides are localized in many human organs and tissues, especially in gastrointestinal tract and kidney, and play an important role in regulation of water and salt homeostasis. Recent studies showed that the mRNA levels of guanylin family peptides were down-regulated in colorectal cancers; oral intake of uroguanylin might suppress polyp formation in Apc(Min/+) mouse, and ~(111)In-labeled-ST peptide analog might specifically target human colon cancers. These evidences highlight that guanylin family may have a potential application in diagnosis and therapy effects of colorectal cancers.