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Objective: To analyze the clinical features and genetic characteristics of two patients with hereditary hemorrhagic telangiectasia (HHT) and to review the relevant literature.Methods: The clinical data of two HHT patients admitted to the author’s hospital between April 2019 and February 2022 were retrospectively analyzed. Meanwhile, the genetic analysis was performed with their consent.Results: The first patient was a 62-year-old woman who had been complaining of shortness of breath and fever for 20 days. Her previous medical history included brain abscess drainage and video-assisted thoracoscopic surgery for a pulmonary hemangioma. A right heart catheterization revealed no pulmonary arterial hypertension, and an abdominal enhanced magnetic resonance imaging revealed multiple arteriovenous malformations in the liver. Her ACVRL1 heterozygous variants were discovered through whole-exon gene testing. The second case involved a 47-year-old woman who had been experiencing chest tightness for the past 2 years. Several years ago, she underwent brain abscess drainage and embolization of a pulmonary arteriovenous fistula. Ultrasound revealed generalized hepatic vascular dilation, and enhanced computed tomography revealed numerous pulmonary venous fistulas scattered in both lungs as well as multiple arteriovenous malformations in the liver. Her whole-exon gene testing revealed that she, like her son, had heterozygous ENG variants.Conclusion: HHT patients may experience infection, bleeding, dyspnea, and other symptoms. Imaging is important in disease diagnosis and management because early detection and treatment can prevent major complications and disability or even death.

Background: The clotting system abnormalities are the common complication in cancer patients. The aim of this retrospective study was to evaluate the coagulation state, clinical features, and treatment in cancer patients by routine tests. Methods: A total of 2328 patients with different types of cancer were classified as the positive group (n = 1419, including 53 patients with thrombosis) and the negative group (n = 909) based on D-dimer (DD) value. Of the 2328 cases, 354 were admitted for chemotherapy. Hemostasis test and complete blood count (CBC) were performed during treatment or following-up. Results: This study showed that the hypercoagulable state was affected not only by clinical staging (P < 0.0001) but also by metastasis site (P < 0.0001 for bone vs. lung). Compared to negative DD group, the higher fibrinogen level, the extended activated partial thromboplastin time, and prothrombin time interacted markedly with disease clinical stage (P < 0.05) in the positive group. Between positive DD groups with and without thrombus, the significantly statistic difference in white blood cell (WBC) and DD (P < 0.05) rather than in red blood cell (RBC) and platelet count was observed. However, the higher DD level was not correlated with WBC, RBC, and platelet count in the positive DD group. Furthermore, the hypercoagulable plasma profile in cancer patients was moderated 2–3 weeks after chemotherapy (P < 0.05 for first six cycles). Conclusions: The routine hemostatic parameters and CBC are valuable to assessment for thrombosis and chemotherapy even for disease prognosis.

Colorectal cancer (CRC) is a worldwide problem for public health. mutL homolog 1 (MLH1) is a key component of the mismatch repair system, and the MLH1-93G/A polymorphism (rs1800734) is predicted to affect MLH1 protein expression, suggesting that the polymorphism may be associated with the cancer risk; however, the results concerning this have been inconsistent. In order to investigate the possible correlation between human (h)MLH1-93G/A polymorphism and the development and progression of sporadic CRC (SCRC) in China, the genotypes of hMLH1-93G/A were detected by the TaqMan MGB probe method in 312 SCRC patients and 300 healthy controls, and immunohistochemical staining was also performed to measure the expression of hMLH1 in cases with different alleles among the SCRC patients and normal controls. It was observed that the A/A genotype and A allele significantly increased the risk of developing Duke's stage C+D CRC and lymphatic metastasis. hMLH1 expression of the A allele was lower than that of the G allele in CRC. By contrast, there was no statistically significant difference in hMLH1 expression for the A allele and the G allele in the normal controls. These results suggested that hMLH1-93G/A polymorphism may not be associated with the overall risk of CRC, but that the hMLH1-93A/A genotype and A allele are associated with the progression of CRC. [ABSTRACT FROM AUTHOR]

The objective of this study was to identify hub genes and pathways associated with hepatocellular carcinoma (HCC) by centrality analysis of a co-expression network. A co-expression network based on differentially expressed (DE) genes of HCC was constructed using the Differentially Co-expressed Genes and Links (DCGL) package. Centrality analyses, for centrality of degree, clustering coefficient, closeness, stress and betweenness for the co-expression network were performed to identify hub genes, and the hub genes were combined together to overcome inconsistent results. Enrichment analyses were conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. Finally, validation of hub genes was conducted utilizing reverse transcription-polymerase chain reaction (RT-PCR) analysis. In total, 260 DE genes between normal controls and HCC patients were obtained and a co-expression network with 154 nodes and 326 edges was constructed. From this, 13 hub genes were identified according to degree, clustering coefficient, closeness, stress and betweenness centrality analysis. It was found that reelin (RELN), potassium voltage-gated channel subfamily J member 10 (KCNJ10) and neural cell adhesion molecule 1 (NCAM1) were common hub genes across the five centralities, and the results of RT-PCR analysis for RELN, KCNJ10 and NCAM1 were consistent with the centrality analyses. Pathway enrichment analysis of DE genes showed that cell cycle, metabolism of xenobiotics by cytochrome P450 and p53 signaling pathway were the most significant pathways. This study may contribute to understanding the molecular pathogenesis of HCC and provide potential biomarkers for its early detection and effective therapies. [ABSTRACT FROM AUTHOR]

Background and Aim: The plasminogen activator/plasmin system is known to regulate the extracellular matrix turnover. The aim of this study was to detect the role of plasminogen activator inhibitor-1 (PAI-1) during liver fibrogenesis and investigate the functional effects of PAI-1 gene silencing in rat hepatic stellate cells (HSCs) using small interfering RNA (siRNA). Methods: Hepatic fibrosis in rats was induced through serial subcutaneously injections of CCl4 and the expression of PAI-1 was detected by immunohistochemistry and reverse transcription–polymerase chain reaction (PCR). PAI-1 siRNA molecules were constructed and transiently transfected into HSC-T6 using the cell suspension transfection method. The pSUPER RNA interfering system was used to establish the HSC stable cell line pSUPER-shPAI. Expression of alpha-smooth muscle actin, transforming growth factor-beta, tissue inhibitor of metalloproteinases-1, and collagen types I and III were evaluated by real-time PCR. Cell proliferation and the cell cycle were determined by the methyl thiazolyl tetrazolium (MTT) method and flow cytometry. Collagen content in HSCs supernatant was evaluated by enzyme-linked immunosorbent assay. Results: The results showed that PAI-1 was upregulated during liver fibrosis, and its expression was closely correlated with the deposition of collagens. SiRNA molecules were successfully transfected into HSCs and induced inhibition of PAI-1 expression time dependently. Moreover, PAI-1 siRNA treatment downregulated alpha-smooth muscle actin, transforming growth factor-beta, tissue inhibitor of metalloproteinases-1 expression, and inhibited collagen types I and III synthesis both at the mRNA and protein level in transiently and stably transfected HSCs. Conclusions: This study suggests a significant functional role for PAI-1 in the development of liver fibrosis and that downregulating PAI-1 expression might present as a potential strategy to treat liver fibrosis. [ABSTRACT FROM AUTHOR]