Image 1.

Occult breast cancer (OBC) refers to a type of breast cancer where no primary lesion is detected through physical examination, imaging, and pathology. This report presents a clinical case of OBC with intestinal obstruction as the initial symptom. A 67-year-old female with no underlying conditions presented to Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University with intestinal obstruction. Contrast-enhanced CT of the abdomen showed thickening of the lower rectum and ascending colon, suggestive of a neoplastic lesion. Chest CT showed multiple enlarged lymph nodes in the left axilla. Colonoscopy revealed only mucosal congestion, roughness, and thickening. Suspecting an intestinal tumor, laparoscopic radical resection of the rectal stenosis was performed. Postoperative pathology indicated poorly differentiated adenocarcinoma of the rectum. Immunohistochemistry showed positive expression of estrogen receptor (ER), progesterone receptor (PR), GATA-binding protein 3 (GATA3), and cytokeratin 7 (CK7), suggesting breast cancer metastasis. Breast MRI revealed multiple proliferative nodules in both breasts (breast imaging reporting and data system, BI-RADS 2). Biopsies of the right lower-inner breast, bilateral axillary, and supraclavicular lymph nodes were performed. No carcinoma was found in the right breast tissues; however, small foci of carcinoma was detected in the right axillary lymph nodes, and poorly differentiated carcinoma of suspected breast origin was found in the bilateral supraclavicular and left axillary lymph nodes. The final diagnosis was OBC with lymph node and rectal metastasis. The patient died 16 months postoperatively. OBC often lacks identifiable primary breast lesions, and gastrointestinal metastases are particularly rare. Clinical manifestations are frequently masked by symptoms of metastatic lesions, making diagnosis challenging. Clinicians should maintain a high index of suspicion. Due to rapid disease progression and multiorgan involvement, prognosis is extremely poor. Early identification of the primary lesion in OBC is crucial for improving outcomes.
Humans ; Female ; Aged ; Intestinal Obstruction/etiology* ; Breast Neoplasms/pathology* ; Adenocarcinoma/diagnosis* ; Neoplasms, Unknown Primary/complications* ; Rectal Neoplasms/complications*

Objective:Construct a combined detection model of miR-202-5p and interleukin-6 (IL-6) and explore its diagnostic value for acute myocardial infarction (AMI).Methods:Clinical data of 202 patients with coronary atherosclerotic heart disease (CHD) who were admitted to the Department of Cardiology and Emergency Department of Hebei People's Hospital from August 2020 to August 2022 were retrospectively analyzed, including 106 AMI patients and 96 non AMI patients. The clinical characteristics and blood levels of miR-202-5p and IL-6 were compared between the two groups, T-test was used for inter group comparison of measurement data that conforms to normal distribution, non parametric rank sum test was used for inter group comparison of measurement data that does not conform to normal distribution, and χ2 test was used for inter group comparison of count data. Binary Logistic regression model was used to determine the independent influencing factors of AMI, and a combined diagnostic model was constructed according to the analysis results, the diagnostic efficacy of miR-202-5p, IL-6 and combined detection for AMI was evaluated by ROC curve, and the clinical diagnostic effect was observed. Results:The expression levels of serum total cholesterol (4.40 (3.71, 5.00) mmol/L), low density lipoprotein cholesterol (2.99 (2.39,3.47) mmol/L), lipoprotein a (276.80 (182.58,390.13) mg/L), interleukin-4(IL-4)(2.69(2.29,3.16) μg/L), IL-6(89.82(68.26,107.16) μg/L) in AMI group were significantly higher than those of non-AMI group (4.04 (3.12, 4.73) mmol/L, 2.75 (2.15, 3.21) mmol/L, 213.45 (146.73, 348.80) mg/L, 2.46 (1.92, 3.01)] μg/L, 45.89 (32.38, 62.83) μg/L, while miR-202-5p(0.33 (0.27,0.38)) was lower than that in the non-AMI group (0.51 (0.36,0.68)), ( H values were 4 167.50, 4 234.00, 4 262.50, 4 228.00, 1 513.00, and 2 098.50, respectively; P values were 0.027, 0.040, 0.047, 0.038, <0.001, <0.001, respectively). Multivariate binary logistic regression analysis showed that high levels of IL-6 and low levels of miR-202-5p were independent risk factors for AMI. The joint diagnostic model of IL-6 and miR-202-5p was Logit (P)=-1.046-5.236 × miR-202-5p+0.051 × IL-6, with probability value P as the diagnostic indicator and P=0.45 as the diagnostic threshold. ROC curve results showed that the area under curve (AUC) of IL-6 and miR-202-5p were 0.851 and 0.794, respectively, while the AUC of the combined diagnosis model was 0.894, indicating that the diagnosis accuracy was higher than that of a single index. Compared with isolated detection, the sensitivity, specificity and Kappa value of the IL-6+miR-202-5p collaborative test for AMI prediction were increased, especially the diagnosis results were close to a high degree of agreement with the actual results ( Kappa=0.732). Conclusion:High levels of IL-6 and low levels of miR-202-5p are independent influencing factors for AMI, and the combined diagnosis model of the two has clinical application value.

Objectives To investigate the regulatory role of miRNA-224-5p in hypoxia/reoxygenation(H/R)-induced H9c2 cardiomyocyte injury.Methods Plasma samples were collected from 160 patients with acute myocardial infarction and 80 healthy controls(HC)to measure miRNA-224-5p levels and other biochemical parameters.In cultured H9c2 cells with H/R injury,the effects of transfection with miR-224-5p mimics or a negative control sequence on cell viability,malondialdehyde(MDA)content,and superoxide dismutase 2(SOD2)and lactate dehydrogenase(LDH)activities were tested.Dual luciferase reporter gene assay was performed to verify the targeting relationship between miR-224-5p and PTEN.Bioinformatics methods were used to analyze the potential mechanisms of the target genes.The expression of miRNA-224-5p in the treated cells was detected with qRT-PCR,the protein expressions of PTEN,Bcl-2,Bax,cleaved caspase-3,SOD2,p-PI3K/PI3K,p-Akt/Ak and p-FoxO1/FoxO1 were determined using Western blotting,and cell apoptosis was analysed with flow cytometry.Results The levels of blood glucose,C-reactive protein,CK,CK-MB and cTnI were significantly higher in the AMI group compared with the HC group(P<0.05).The expression level of miR-224-5p was significantly lowered in patients with STEMI and NSTEMI and in H9c2 cells with H/R injury.The viability of H9c2 cells decreased time-dependently following H/R injury.PTEN was a target gene of miR-224-5p,and the PI3K/Akt pathway was the most significantly enriched pathway.H9c2 cells with H/R injury showed significantly decreased SOD2 activity,increased LDH activity and MDA content,increased cell apoptosis,decreased protein expression levels of p-PI3K,p-Akt,p-FoxO1,SOD2,and Bcl-2,and increased expressions of PTEN,Bax,and cleaved caspase-3.These changes were obviously attenuated by trasnfection of the cells with miR-224-5p mimics prior to H/R exposure.Conclusion MiR-224-5p overexpression upregulates the expression of the antioxidant gene SOD2 through the PI3K/Akt/FoxO1 axis to relieve H/R-induced oxidative stress and reduce apoptosis of H9c2 cells.

Objective To evaluate the potential of miR-30a-5p as a novel indicator of acute myocardial infarction(AMI)and the underlying molecular mechanisms.Methods AMI-associated microRNAs(miRNAs)and mRNA microarray datasets were downloaded from the GEO database.Real-time fluorescence quantitative PCR(qRT-PCR)technique was used to detect the level of miRNAs in serum samples;automatic biochemistry was used to detect other biochemical indicators.Receiver operating characteristic(ROC)curve analysis and Spearson correlation analysis were performed to assess the value of miR-30a-5p as a diagnostic AMI marker.The target genes of miR-30a-5p were predicted with the R language multiMiR package,and the protein interaction network was constructed by the STRING database.The results were imported into Cytoscape 3.7.1 software to screen the pivotal genes of the network.The R language clusterProfiler package performed KEGG and GO analyses on the hub genes to explore the clinical significance of miR-30a-5p in AMI and its potential molecular mechanisms.Results Compared with the control group,miR-30a-5p was upregulated significantly in the serum of patients in the AMI group(P＜0.05);miR-30a-5p was positively correlated with the levels of CK-MB,CK,TnT,proBNP and CRP(rs=0.489,P＜0.001;rs=0.347,P＜0.001;rs=0.545,P＜0.001;rs=0.533,P＜0.001;rs=0.206,P＜0.05).The area under the ROC curve was 0.862,with sensitivity of 84.4％and specificity of 74.2％.A total of 780 differentially expressed genes(DEGs)were obtained from the two datasets.A total of 1 061 target genes of miR-30a-5p and 61 common genes were identified by taking the intersection set.Among the central genes of PPI,BCL6,FOSL2,JDP2,LYN,PDE4D,SOCS3 and SOX4 scored high and were closely associated with the occurrence of AMI.KEGG and GO enrichment analyses showed that miR-30a-5p might regulate JAK-STAT,NF-kappaB and Wnt signaling pathways,which were involved in inflammatory response,apoptosis,autophagy and post-infarction remodeling,and thus participated in the process of AMI.Conclusion Serum miR-30a-5p is up-regulated in the early stage of AMI,and the study on miR-30a-5p and its regulatory pathways can help with the diagnosis and treatment of myocardial infarction.

Objectives To investigate the regulatory role of miRNA-224-5p in hypoxia/reoxygenation(H/R)-induced H9c2 cardiomyocyte injury.Methods Plasma samples were collected from 160 patients with acute myocardial infarction and 80 healthy controls(HC)to measure miRNA-224-5p levels and other biochemical parameters.In cultured H9c2 cells with H/R injury,the effects of transfection with miR-224-5p mimics or a negative control sequence on cell viability,malondialdehyde(MDA)content,and superoxide dismutase 2(SOD2)and lactate dehydrogenase(LDH)activities were tested.Dual luciferase reporter gene assay was performed to verify the targeting relationship between miR-224-5p and PTEN.Bioinformatics methods were used to analyze the potential mechanisms of the target genes.The expression of miRNA-224-5p in the treated cells was detected with qRT-PCR,the protein expressions of PTEN,Bcl-2,Bax,cleaved caspase-3,SOD2,p-PI3K/PI3K,p-Akt/Ak and p-FoxO1/FoxO1 were determined using Western blotting,and cell apoptosis was analysed with flow cytometry.Results The levels of blood glucose,C-reactive protein,CK,CK-MB and cTnI were significantly higher in the AMI group compared with the HC group(P<0.05).The expression level of miR-224-5p was significantly lowered in patients with STEMI and NSTEMI and in H9c2 cells with H/R injury.The viability of H9c2 cells decreased time-dependently following H/R injury.PTEN was a target gene of miR-224-5p,and the PI3K/Akt pathway was the most significantly enriched pathway.H9c2 cells with H/R injury showed significantly decreased SOD2 activity,increased LDH activity and MDA content,increased cell apoptosis,decreased protein expression levels of p-PI3K,p-Akt,p-FoxO1,SOD2,and Bcl-2,and increased expressions of PTEN,Bax,and cleaved caspase-3.These changes were obviously attenuated by trasnfection of the cells with miR-224-5p mimics prior to H/R exposure.Conclusion MiR-224-5p overexpression upregulates the expression of the antioxidant gene SOD2 through the PI3K/Akt/FoxO1 axis to relieve H/R-induced oxidative stress and reduce apoptosis of H9c2 cells.

Abdominal aortic aneurysm(AAA)is a hidden and fatal disease,but its underlying developmental mechanism remains unclear.Phenotypic switching of vascular smooth muscle cells and pyroptosis have been identified as biological processes closely related to the appearance and progression of AAA,with potentially important roles in the mechanism of AAA and in providing new directions for its diagnosis and treatment.In this review,we discuss phenotypic switching of vascular smooth muscle cells and the regulatory relationship between cell pyroptosis and AAA.

Abdominal aortic aneurysm(AAA)is a hidden and fatal disease,but its underlying developmental mechanism remains unclear.Phenotypic switching of vascular smooth muscle cells and pyroptosis have been identified as biological processes closely related to the appearance and progression of AAA,with potentially important roles in the mechanism of AAA and in providing new directions for its diagnosis and treatment.In this review,we discuss phenotypic switching of vascular smooth muscle cells and the regulatory relationship between cell pyroptosis and AAA.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting both upper and lower motor neurons (MNs) with large unmet medical needs. Multiple pathological mechanisms are considered to contribute to the progression of ALS, including neuronal oxidative stress and mitochondrial dysfunction. Honokiol (HNK) has been reported to exert therapeutic effects in several neurologic disease models including ischemia stroke, Alzheimer's disease and Parkinson's disease. Here we found that honokiol also exhibited protective effects in ALS disease models both in vitro and in vivo. Honokiol improved the viability of NSC-34 motor neuron-like cells that expressed the mutant G93A SOD1 proteins (SOD1-G93A cells for short). Mechanistical studies revealed that honokiol alleviated cellular oxidative stress by enhancing glutathione (GSH) synthesis and activating the nuclear factor erythroid 2-related factor 2 (NRF2)-antioxidant response element (ARE) pathway. Also, honokiol improved both mitochondrial function and morphology via fine-tuning mitochondrial dynamics in SOD1-G93A cells. Importantly, honokiol extended the lifespan of the SOD1-G93A transgenic mice and improved the motor function. The improvement of antioxidant capacity and mitochondrial function was further confirmed in the spinal cord and gastrocnemius muscle in mice. Overall, honokiol showed promising preclinical potential as a multiple target drug for ALS treatment.

Globally, the incidence of pancreatic cancer is on a rise. Pancreatic cancer is characterized by difficulty in early diagnosis, frequent distant metastasis, low surgical resection rate, and high risk of postoperative recurrence. Better treatments need to be developed to prolong the prognosis. Studies have confirmed that inflammation is closely correlated with tumorigenesis, and inflammatory mediators play important roles on tumor microenvironment of pancreatic cancer and lead to poor prognosis. This article reviewed the progress on the correlation between peripheral blood inflammatory index and the prognosis of pancreatic cancer.