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The timely identification of individuals at high risk for peptic ulcers (PUs) is vital in preventing gastrointestinal bleeding after antiplatelet therapy. This study was designed to determine PU risk factors and develop a risk assessment model for PU detection in the general Chinese population. In a prospective dataset, clinical data from individuals undergoing gastroscopic evaluation between April 2019 and May 2022 were recorded. PUs were defined as mucosal defects exceeding 5 mm confirmed via gastroscopy. Participants were categorized into development (April 2019 to April 2021) and validation (May 2021 to May 2022) sets based on chronological order. LASSO-derived logistic regression analysis was employed to create a score, which was further validated via temporal validation. A total of 902 patients were ultimately enrolled, 204 (22.6%) of whom had PUs based on endoscopic findings. In the development cohort (n = 631), seven independent risk factors emerged: male sex (OR = 2.35, P = 0.002), white blood cell (WBC) count (OR = 1.16, P = 0.010), red blood cell (RBC) count (OR = 0.49, P < 0.001), globulin level (OR = 0.92, P = 0.004), albumin level (OR = 0.94, P = 0.020), pepsinogen I (PGI) level (OR = 1.01, P < 0.001), and positive Helicobacter pylori (HP) antibody (OR = 2.50, P < 0.001). Using these factors, a nomogram (HAMPROW score [hazard ratio (HP) antibody, albumin, male, PGI, RBC, globulin, and WBC]) was developed for individual PU prediction. The ability of the HAMPROW score to predict survival was confirmed with AUCs of 0.854 (95% CI 0.816-0.891) and 0.833 (95% CI 0.771-0.895) in the development and validation sets, respectively. In conclusion, the HAMPROW score can be used to screen for PUs effectively in the general Chinese population, facilitating personalized early detection of high risk of gastrointestinal bleeding before antiplatelet therapy.
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Globulinas , Infecciones por Helicobacter , Helicobacter pylori , Úlcera Péptica , Humanos , Masculino , Úlcera Péptica Hemorrágica/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Estudios Prospectivos , Úlcera Péptica/complicaciones , Hemorragia Gastrointestinal/inducido químicamente , Albúminas/uso terapéutico , China/epidemiología , Supuración/inducido químicamente , Supuración/complicaciones , Infecciones por Helicobacter/tratamiento farmacológicoRESUMEN
Optical coherence tomography angiography (OCTA), as a new generation of non-invasive and efficient fundus imaging technology, can provide non-invasive assessment of vascular lesions in the retina and choroid. In terms of anatomy and development, the retina is referred to as an extension of the central nervous system (CNS). CNS diseases are closely related to changes in fundus structure and blood vessels, and direct visualization of fundus structure and blood vessels provides an effective "window" for CNS research. This has important practical significance for identifying the characteristic changes of various CNS diseases on OCTA in the future, and plays a key role in promoting early screening, diagnosis, and monitoring of disease progression in CNS diseases. This article reviews relevant fundus studies by comparing and summarizing the unique advantages and existing limitations of OCTA in various CNS disease patients, in order to demonstrate the clinical significance of OCTA in the diagnosis and treatment of CNS diseases.
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BACKGROUND: Extracellular matrix (ECM) remodeling and stiffening, which are correlated with tumor malignancy, drives tumor development. However, the relationship between ECM remodeling and rat experimental model of 1,2-dimethylhyrazine (DMH)-induced colorectal cancer (CRC) imposed by cold and capsaicin exposure remains unclear. AIM: To explore the effects of cold exposure and capsaicin on ECM remodeling and ECM enzymes in DMH-induced CRC. METHODS: For histopathological analysis, the sections of colon tissues were stained with hematoxylin and eosin, Masson's trichrome, Picrosirius red, and Weigert's Resorcin-Fuchsin to observe the remodeling of collagen and elastin. Additionally, the protein expression level of type I collagen (COL I), type 3 collagen (COL III0, elastin, matrix metalloproteinase (MMP) 1, MMP2, MMP9, and tissue-specific matrix metalloproteinase 1 (TIMP1) was assessed by immunohistochemistry. The messenger RNA (mRNA) levels of COL I, COL III, elastin, and lysyl oxidase-like-2 (LOXL2) in the colon tissues of rats was measured by reverse-transcriptase quantitative polymerase chain reaction. RESULTS: Although no differences were observed in the proportion of adenomas, a trend towards the increase of invasive tumors was observed in the cold and capsaicin group. The cold exposure group had a metastasis rate compared with the other groups. Additionally, abnormal accumulation of both collagen and elastin was observed in the cold exposure and capsaicin group. Specifically, collagen quantitative analysis showed increased length, width, angle, and straightness compared with the DMH group. Collagen deposition and straightness were significantly increased in the cold exposure group compared with the capsaicin group. Cold exposure and capsaicin significantly increased the protein levels of COL I, elastin, and LOXL2 along with increases in their mRNA levels in the colon tissues compared with the DMH group, while COL III did not show a significant difference. Furthermore, in immunohistochemical evaluations, MMP1, MMP2, MMP9, and TIMP1 staining increased in the cold exposure and capsaicin group compared with the DMH group. CONCLUSION: These results suggest that chronic cold and capsaicin exposure further increased the deposition of collagen and elastin in the colonic tissue. Increased COL I and elastin mRNA and protein levels expression may account for the enhanced ECM remodel and stiffness variations of colon tissue. The upregulated expression of the LOXL2 and physiological imbalance between MMP/TIMP activation and deactivation could contribute to the progression of the CRC resulting from cold and capsaicin exposure.
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Capsaicina , Matriz Extracelular , Animales , Capsaicina/farmacología , Carcinogénesis , Colon , Metaloproteinasa 2 de la Matriz/genética , RatasRESUMEN
Previous studies have indicated that capsaicin-rich diet and cold weather have shown strong association with tumor incidence. Thus, we investigated the effects of capsaicin and cold exposure in 1,2-dimethylhydrazine (DMH)-induced colorectal cancer as well as the mechanisms underlying capsaicin and cold-induced CRC. Rats were randomly divided into four groups and received cold still water and capsaicin via intragastric gavage until the end of the experiment. The rat's body weight, thymus weight, and food intakes were assessed. Global levels of histone H3K9, H3K18, H3K27, and H4K16 acetylation and histone deacetylase (HDACs) in colon mucosa were assessed by western blot. Expression levels of Toll-like receptors 2 (TLR2) and Toll-like receptors 4 (TLR4) were measured by western blot and reverse-transcriptase quantitative polymerase chain reaction (qPCR). We found that cold and low-dose capsaicin increased tumor numbers and multiplicity, although there were no differences in tumor incidence. Additionally, rat exposure to cold water and capsaicin display further higher levels of histone H3 lysine 9 (H3K9AC), histone H3 lysine 18 (H3K18AC), histone H3 lysine 27 (H3K27AC), and HDACs compared with the DMH and normal rats. In contrast, a considerable decrease of histone H4 lysine 16 (H4K16AC) was detected in the colon mucosa. Cold and low-dose capsaicin exposure groups were also increased TLR2 and TLR4 protein levels and mRNA levels. These results suggest that chronic cold exposure and capsaicin at a low-dose intervention exacerbate ectopic expression of global histone acetylation and TLR level, which are crucial mechanisms responsible for the progression of colorectal cancer in rats.
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Capsaicina , Neoplasias del Colon/metabolismo , Histonas , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 4/metabolismo , 1,2-Dimetilhidrazina , Acetilación , Animales , Capsaicina/farmacología , Carcinogénesis , Colon/metabolismo , Neoplasias del Colon/inducido químicamente , Histonas/metabolismo , RatasRESUMEN
The development of colorectal cancer is a complex and multistep process mediated by a variety of factors including the dysregulation of genetic and epigenetic under the influence of microenvironment. It is evident that epigenetics that affects gene activity and expression has been recognized as a critical role in the carcinogenesis. Aside from DNA methylation, miRNA level, and genomic imprinting, histone modification is increasingly recognized as an essential mechanism underlying the occurrence and development of colorectal cancer. Aberrant regulation of histone modification like acetylation, methylation and phosphorylation levels on specific residues is implicated in a wide spectrum of cancers, including colorectal cancer. In addition, as this process is reversible and accompanied by a plethora of deregulated enzymes, inhibiting those histone-modifying enzymes activity and regulating its level has been thought of as a potential path for tumor therapy. This review provides insight into the basic information of histone modification and its application in the colorectal cancer treatment, thereby offering new potential targets for treatment of colorectal cancer.