Extracorporeal membrane oxygenation states basilar artery thrombectomy and left posterior cerebral artery stent thrombectomy: A case report.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a new type of extracorporeal respiratory and circulatory assistance device. It can drain venous blood out of the body and inject it into veins or arteries after being oxygenated by an oxygenator (membrane lung) to replace lung and heart functions in a short time. ECMO can provide tissue blood perfusion and gas exchange almost equivalent to cardiac output and extend the effective treatment time window for patients with acute circulatory failure to restore cardiopulmonary function. CASE SUMMARY: We report a case of an 81-year-old woman who underwent whole cerebral angiography, basilar artery thrombectomy and stent thrombectomy in the posterior artery of the left brain after implantation of ECMO. The patient was admitted to the hospital due to myocardial infarction. Considering that the cause of the patient's disturbance of consciousness was unknown and cerebrovascular accident could not be ruled out after the implantation of ECMO, the department of Radioactive Intervention performed cerebral angiography. And the result of the angiography indicated vascular occlusion. After the basilar artery thrombectomy and stent thrombectomy in the posterior artery of the left brain, the patency of the occlusive vessel was achieved. CONCLUSION: Although the patient eventually died of circulatory failure, the result of this case verifies the feasibility of cerebral angiography and thrombectomy in patients with implanted ECMO in the intubated state.

Diagnostic value of carbohydrate antigen 50 in biliary tract cancer: A large-scale multicenter study.

BACKGROUND: To date, carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) have been widely used for the screening, diagnosis and prediction of biliary tract cancer (BTC) patients. However, few studies with large sample sizes of carbohydrate antigen 50 (CA50) were reported in BTC patients. METHODS: A total of 1121 patients from the Liver Cancer Clin-Bio Databank of Anhui Hepatobiliary Surgery Union between January 2017 and December 2022 were included in this study (673 in the training cohort and 448 in the validation cohort): among them, 458 with BTC, 178 with hepatocellular carcinoma (HCC), 23 with combined hepatocellular-cholangiocarcinoma, and 462 with nontumor patients. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were used to evaluate the diagnostic efficacy and clinical usefulness. RESULTS: ROC curves obtained by combining CA50, CA19-9, and AFP showed that the AUC value of the diagnostic MODEL 1 was 0.885 (95% CI 0.856-0.885, specificity 70.3%, and sensitivity 84.0%) in the training cohort and 0.879 (0.841-0.917, 76.7%, and 84.3%) in the validation cohort. In addition, comparing iCCA and HCC (235 in the training cohort, 157 in the validation cohort), the AUC values of the diagnostic MODEL 2 were 0.893 (95% CI 0.853-0.933, specificity 96%, and sensitivity 68.6%) in the training cohort and 0.872 (95% CI 0.818-0.927, 94.2%, and 64.6%) in the validation cohort. CONCLUSION: The model combining CA50, CA19-9, and AFP not only has good diagnostic value for BTC but also has good diagnostic value for distinguishing iCCA and HCC.

Adjuvant donafenib for hepatocellular carcinoma patients at high-risk of recurrence after radical resection: a real-world experience.

Background: Adjuvant therapy is used to reduce the risk of hepatocellular carcinoma (HCC) recurrence and improve patient prognosis. Exploration of treatment strategies that are both efficacious and safe has been extensively performed in the recent years. Although donafenib has demonstrated good efficacy in the treatment of advanced HCC, its use as adjuvant therapy in HCC has not been reported. Objectives: To investigate the efficacy and safety of postoperative adjuvant donafenib treatment in patients with HCC at high-risk of recurrence. Design: Retrospective study. Methods: A total of 196 patients with HCC at high-risk of recurrence were included in this study. Of these, 49 received adjuvant donafenib treatment, while 147 did not. Survival outcomes and incidence of adverse events (AEs) in the donafenib-treated group were compared. Inverse probability of treatment weighting (IPTW) method was used. Results: The median follow-up duration was 21.8 months [interquartile range (IQR) 17.2-27.1]. Before IPTW, the donafenib-treated group exhibited a significantly higher 1-year recurrence-free survival (RFS) rate (83.7% versus 66.7%, p = 0.023) than the control group. Contrarily, no significant difference was observed in the 1-year overall survival (OS) rates between the two groups (97.8% versus 91.8%, p = 0.120). After IPTW, the 1-year RFS and OS rates (86.6% versus 64.8%, p = 0.004; 97.9% versus 89.5%, p = 0.043, respectively) were higher than those in the control group. Multivariate analysis revealed that postoperative adjuvant donafenib treatment was an independent protective factor for RFS. The median duration of adjuvant donafenib treatment was 13.6 (IQR, 10.7-18.1) months, with 44 patients (89.8%) experienced AEs, primarily grade 1-2 AEs. Conclusion: Postoperative adjuvant donafenib treatment effectively reduced early recurrence among patients with HCC at high-risk of recurrence, while exhibiting favorable safety and tolerability profile. However, these findings warrant further investigation.

Comparison of the outcomes of patients with HCC with or without donafenib after radical resection to better understand the efficacy and safety of postoperative adjuvant donafenib Why was this study done? Donafenib is the only new-generation targeted drug developed in the past 14 years that has demonstrated superior efficacy and increased safety in the first-line treatment of HCC. We aimed to explore whether postoperative adjuvant donafenib can improve the prognosis of patients with HCC at high-risk of recurrence. What did the researchers do? Medical data of patients with HCC at high-risk of recurrence who underwent radical resection at two medical centers between April 2021 and October 2022 were collected to compare long-term outcomes of patients treated with and without donafenib and explore the safety of adjuvant donafenib treatment. What did the researchers find? A total of 196 patients with HCC at high-risk of recurrence, including 49 who received adjuvant donafenib treatment and 147 who did not, were analyzed. At a median follow-up of 21.8 months, it was observed that adjuvant donafenib treatment effectively reduced early recurrence among patients with HCC at high-risk of recurrence, while exhibiting favorable safety and compliance profiles. What do the findings mean? The study provides real-world clinical empirical data on adjuvant donafenib treatment for patients with HCC at high-risk of recurrence, and these results may provide new directions for adjuvant treatment of HCC.

Progress in the study of autophagy-related proteins affecting resistance to chemotherapeutic drugs in leukemia.

Leukemia is a life-threatening malignant tumor of the hematopoietic system. Currently, the main treatment modalities are chemotherapy and hematopoietic stem cell transplantation. However, increased drug resistance due to decreased sensitivity of leukemia cells to chemotherapeutic drugs presents a major challenge in current treatments. Autophagy-associated proteins involved in autophagy initiation have now been shown to be involved in the development of various types of leukemia cells and are associated with drug resistance. Therefore, this review will explore the roles of autophagy-related proteins involved in four key autophagic processes: induction of autophagy and phagophore formation, phagophore extension, and autophagosome formation, on the development of various types of leukemias as well as drug resistance. Autophagy may become a promising therapeutic target for treating leukemia.

Tumour response following preoperative chemotherapy is affected by body mass index in patients with colorectal liver metastases.

BACKGROUND: Colorectal cancer is the third most prevalent malignancy globally and ranks second in cancer-related mortality, with the liver being the primary organ of metastasis. Preoperative chemotherapy is widely recommended for initially or potentially resectable colorectal liver metastases (CRLMs). Tumour pathological response serves as the most important and intuitive indicator for assessing the efficacy of chemotherapy. However, the postoperative pathological results reveal that a considerable number of patients exhibit a poor response to preoperative chemotherapy. Body mass index (BMI) is one of the factors affecting the tumorigenesis and progression of colorectal cancer as well as prognosis after various antitumour therapies. Several studies have indicated that overweight and obese patients with metastatic colorectal cancer experience worse prognoses than those with normal weight, particularly when receiving first-line chemotherapy regimens in combination with bevacizumab. AIM: To explore the predictive value of BMI regarding the pathologic response following preoperative chemotherapy for CRLMs. METHODS: A retrospective analysis was performed in 126 consecutive patients with CRLM who underwent hepatectomy following preoperative chemotherapy at four different hospitals from October 2019 to July 2023. Univariate and multivariate logistic regression models were applied to analyse potential predictors of tumour pathological response. The Kaplan-Meier method with log rank test was used to compare progression-free survival (PFS) between patients with high and low BMI. BMI < 24.0 kg/m2 was defined as low BMI, and tumour regression grade 1-2 was defined as complete tumour response. RESULTS: Low BMI was observed in 74 (58.7%) patients and complete tumour response was found in 27 (21.4%) patients. The rate of complete tumour response was significantly higher in patients with low BMI (29.7% vs 9.6%, P = 0.007). Multivariate analysis revealed that low BMI [odds ratio (OR) = 4.56, 95% confidence interval (CI): 1.42-14.63, P = 0.011], targeted therapy with bevacizumab (OR = 3.02, 95%CI: 1.10-8.33, P = 0.033), preoperative carcinoembryonic antigen level < 10 ng/mL (OR = 3.84, 95%CI: 1.19-12.44, P = 0.025) and severe sinusoidal dilatation (OR = 0.17, 95%CI: 0.03-0.90, P = 0.037) were independent predictive factors for complete tumour response. The low BMI group exhibited a significantly longer median PFS than the high BMI group (10.7 mo vs 4.7 mo, P = 0.011). CONCLUSION: In CRLM patients receiving preoperative chemotherapy, a low BMI may be associated with better tumour response and longer PFS.

Nurses' perspectives on workplace environment needs associated to resilience: a qualitative descriptive study.

Objective: The purpose of this study was to explore the demands of nurses on the workplace environment related to psychological resilience. Methods: A qualitative descriptive design was employed for this study. Purposeful sampling was chosen from a tertiary hospital in Henan Province, China. Semi-structured in-depth interviews were conducted with 20 nurses. The interview data was analyzed using the Colaizzi's method and results were reported following the COREQ standards. Results: Analysis of the interview data revealed three main themes: (1) Career Support and Development, (2) Practical Support & Development, and (3) Personal Support and Development. Conclusion: The perspectives of nurses for a workplace environment demands needs to be appreciated, and in addition, it is worth noting that the key role of building a good workplace environment in strengthening the resilience of nurses emphasizes the need for careful consideration. Nursing administrators should formulate policies and measures from multiple perspectives based on the real needs of nurses in terms of professional, practical, and personal dimensions.

HOXC13-driven TIMM13 overexpression promotes osteosarcoma cell growth.

TIMM13 (translocase of inner mitochondrial membrane 13) located at the mitochondrial intermembrane space is vital for the integrity and function of mitochondria. We found that the mitochondrial protein TIMM13 is upregulated in human OS tissues and cells. In patient-derived primary OS cells and established cell lines, TIMM13 shRNA or knockout provoked mitochondrial dysfunction, causing mitochondrial depolarization, reactive oxygen species production, and oxidative injury, as well as lipid peroxidation, DNA damage, and ATP depletion. Moreover, TIMM13 depletion provoked OS cell apoptosis and inhibited cell proliferation and migration. Conversely, ectopic TIMM13 overexpression increased ATP contents, enhancing OS cell proliferation and migration. Moreover, we discovered that Akt-mTOR activation was inhibited with TIMM13 depletion in primary OS cells. Further studies revealed that HOXC13 (Homeobox C13)-dependent TIMM13 transcription was significantly increased in OS tissues and cells. Whereas TIMM13 transcription and expression were decreased following HOXC13 silencing in primary OS cells. In vivo, TIMM13 KO potently inhibited OS xenograft growth in the proximal tibia of nude mice. TIMM13 KO also induced Akt-mTOR inactivation, ATP depletion, oxidative injury, and apoptosis in the in situ OS tumors. Together, upregulation of the mitochondrial protein TIMM13 is important for OS cell growth, representing a novel and promising therapeutic target.

Brown tumor of the cervical spine with primary hyperparathyroidism: A case report and literature review.

RATIONALE: Brown tumor (BT), an uncommon focal lytic bone tumor, is a non-neoplastic and reactive process caused by increased osteoclastic activity and fibroblastic proliferation in primary or secondary hyperparathyroidism. Vertebral tumor causing neural compression is relatively rare, especially in the cervical spine. PATIENT CONCERNS: A 29-year-old man developed neck pain and arm radicular pain 4 months ago, with the level of serum calcium significantly higher than normal. Computed tomography scan of the cervical spine revealed an expansile lytic lesion occupying the C6 body, left pedicle, and left lamina of C5-6. DIAGNOSES: Osteoclastoma according to imaging and histopathological results. INTERVENTIONS: A laminectomy of C5-6 was performed. OUTCOMES: One month later, he was re-hospitalized due to nausea and vomiting and the serum calcium, was still, kept at a high level. Additionally, the parathormone (PTH) was greatly higher than normal. BT with primary hyperparathyroidism due to the parathyroid tumor was considered. After the surgery of the right parathyroid gland was performed, serum calcium and PTH both decreased, and computed tomography showed good recovery. LESSONS: BTs might be misdiagnosed as other giant cell tumors, thus when giant cell tumors are considered, serum calcium and PTH examination may be needed to exclude BTs.

Identification of a tumour immune barrier in the HCC microenvironment that determines the efficacy of immunotherapy.

BACKGROUND & AIMS: The tumour microenvironment (TME) is a crucial mediator of cancer progression and therapeutic outcome. The TME subtype correlates with patient response to immunotherapy in multiple cancers. Most previous studies have focused on the role of different cellular components in the TME associated with immunotherapy efficacy. However, the specific structure of the TME and its role in immunotherapy efficacy remain largely unknown. METHODS: We combined spatial transcriptomics with single-cell RNA-sequencing and multiplexed immunofluorescence to identify the specific spatial structures in the TME that determine the efficacy of immunotherapy in patients with hepatocellular carcinoma (HCC) receiving anti-PD-1 treatment. RESULTS: We identified a tumour immune barrier (TIB) structure, a spatial niche composed of SPP1+ macrophages and cancer-associated fibroblasts (CAFs) located near the tumour boundary, which is associated with the efficacy of immune checkpoint blockade. Furthermore, we dissected ligand‒receptor networks among malignant cells, SPP1+ macrophages, and CAFs; that is, the hypoxic microenvironment promotes SPP1 expression, and SPP1+ macrophages interact with CAFs to stimulate extracellular matrix remodelling and promote TIB structure formation, thereby limiting immune infiltration in the tumour core. Preclinically, the blockade of SPP1 or macrophage-specific deletion of Spp1 in mice led to enhanced efficacy of anti-PD-1 treatment in mouse liver cancer, accompanied by reduced CAF infiltration and increased cytotoxic T-cell infiltration. CONCLUSIONS: We identified that the TIB structure formed by the interaction of SPP1+ macrophages and CAFs is related to immunotherapy efficacy. Therefore, disruption of the TIB structure by blocking SPP1 may be considered a relevant therapeutic approach to enhance the therapeutic effect of immune checkpoint blockade in HCC. IMPACT AND IMPLICATIONS: Only a limited number of patients with hepatocellular carcinoma (HCC) benefit from tumour immunotherapy, which significantly hinders its application. Herein, we used multiomics to identify the spatial structure of the tumour immune barrier (TIB), which is formed by the interaction of SPP1+ macrophages and cancer-associated fibroblasts in the HCC microenvironment. This structure constrains immunotherapy efficacy by limiting immune cell infiltration into malignant regions. Preclinically, we revealed that blocking SPP1 or macrophage-specific deletion of Spp1 in mice could destroy the TIB structure and sensitize HCC cells to immunotherapy. These results provide the first key steps towards finding more effective therapies for HCC and have implications for physicians, scientists, and drug developers in the field of HCC.

3D printing of bone and cartilage with polymer materials.

Damage and degeneration to bone and articular cartilage are the leading causes of musculoskeletal disability. Commonly used clinical and surgical methods include autologous/allogeneic bone and cartilage transplantation, vascularized bone transplantation, autologous chondrocyte implantation, mosaicplasty, and joint replacement. 3D bio printing technology to construct implants by layer-by-layer printing of biological materials, living cells, and other biologically active substances in vitro, which is expected to replace the repair mentioned above methods. Researchers use cells and biomedical materials as discrete materials. 3D bio printing has largely solved the problem of insufficient organ donors with the ability to prepare different organs and tissue structures. This paper mainly discusses the application of polymer materials, bio printing cell selection, and its application in bone and cartilage repair.

Clinical efficacy of avatrombopag and recombinant human thrombopoietin in the treatment of chronic liver disease-associated severe thrombocytopenia: A real-world study.

Purpose: To investigate the clinical efficacy of avatrombopag, an oral thrombopoietin receptor agonist, versus subcutaneous recombinant human thrombopoietin (rh-TPO) in the treatment of severe thrombocytopenia (TCP) associated with chronic liver disease (CLD). Methods: Clinical data of 250 patients with severe TCP associated with CLD were collected in a single hospital from January 2019 to January 2022. The main parameters measured were the therapeutic response rate, changes in platelets (PLTs), and adverse events. Propensity score matching (PSM) was used to avoid possible selection bias. Results: After PSM, a total of 154 patients were enrolled in the study: 77 in the avatrombopag group and 77 in the rh-TPO group. There was no statistically significant difference between the two groups in the effect of increasing the PLT count (Waldχ 2 = 1.659, p = 0.198; Waldχ 2 = 0.220, p = 0.639). In addition, no interaction between time and different medications was found (Waldχ 2 = 0.540, p = 0.910; Waldχ 2 = 1.273, p = 0.736). Interestingly, in the subgroup analysis, both before and after PSM, avatrombopag showed better clinical efficacy than rh-TPO in the treatment of TCP associated with CLD in Child‒Pugh Class A (88.89% vs. 63.41%, p =0.003; 81.33% vs. 61.76%, p = 0.043). Fewer patients reported dizziness in the avatrombopag group than in the rh-TPO group both before and after PSM (7.8% vs. 25.0%; 7.8% vs. 24.7%, p < 0.05). Conclusion: Both before and after PSM, avatrombopag showed better clinical efficacy than rh-TPO in the treatment of TCP associated with CLD in Child‒Pugh Class A and showed a lower incidence of dizziness in all patients.

[Retracted] MicroRNA­873 targets HOXA9 to inhibit the aggressive phenotype of osteosarcoma by deactivating the Wnt/ß­catenin pathway.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that various panels showing the data from flow cytometry experiments in Figs. 2D, 5D and 6D, and certain of the migration assay data shown in Fig. 7A, were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article were already under consideration for publication prior to its submission to International Journal of Oncology, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 54: 1809­1820, 2019; DOI: 10.3892/ijo.2019.4735].

The Drug Coated Balloon-Only Strategy for Treatment of de Novo Left Main Coronary Artery Bifurcation Lesion: Stentless Strategy.

The study aimed to evaluate the efficacy and safety of drug coated balloon-only strategy (DCB-only) in the treatment of de novo left main coronary artery (LM) bifurcation lesions. 85 patients were enrolled in this study and classified them into two groups: DCB-only group (n = 36) and DES group (n = 49). The MLD of target vessels was measured before and immediately after percutaneous coronary intervention (PCI) and late luminal loss (LLL) were also calculated. And the occurrence of major adverse cardiovascular events (MACE) was also evaluated. Compared with that before PCI, the MLD of target lesions significantly increased immediately after PCI (P < .05) and no MACE was recorded during the perioperative period both in two groups. The MLD at follow-up was significantly higher than that before both DCB and DES treatment. Compared with the DES group, the MLD of the DCB group was smaller than immediately after PCI in the LM and LAD (P < .05). The LLL of LAD in DCB group was smaller than that in DES group (P < .05). There was no significant difference in the incidence of luminal restenosis at the target lesion between the two groups, and no significant difference in the incidence of MACE (P > .05). The use of DCB-only to treat de novo LM bifurcation lesions is effective and relatively safe, which provides new ideas for the treatment of LM coronary artery bifurcation lesions in the future.

Multi-organ metastasis as destination for breast cancer cells guided by biomechanical architecture.

A majority of breast cancer patients die of widespread aggressive multidrug-resistant tumors. Aspartate ß-hydroxylase (ASPH) is an α-ketoglutarate-dependent dioxygenase and oncofetal antigen involved in embryogenesis. To illustrate if ASPH could be targeted for metastatic breast cancer, embedded and on-top three-dimensional (3-D) cultures, 3-D invasion, mammosphere formation, immunofluorescence, immunohistochemistry, Western blot, co-IP and microarray were conducted. In vitro metastasis was developed to imitate how cancer cells invade basement membrane at the primary site, transendothelially migrate, consequently colonize and outgrow at distant sites. Orthotopic and experimental pulmonary metastatic (tail vein injection) murine models were established using stable breast cancer cell lines. Cox proportional hazards regression models and Kaplan-Meier plots were applied to assess clinical outcome of breast cancer patients. In adult non-cancerous breast tissue, ASPH is undetectable. Pathologically, ASPH expression re-emerged at ductal carcinoma in situ (DCIS), and enhanced with disease progression, from early-stage invasive ductal carcinoma (IDC) to late-stage carcinoma. ASPH at moderate to high levels contribute to aggressive molecular subtypes, early relapse or more frequent progression and metastases, whereas substantially shortened overall survival and disease-free survival of breast cancer patients. Through direct physical interactions with A disintegrin and metalloproteinase domain-containing protein (ADAM)-12/ADAM-15, ASPH could activate SRC cascade, thus upregulating downstream components attributed to multifaceted metastasis. ASPH-SRC axis initiated pro-invasive invadopodium formation causing breakdown/disorganization of extracellular matrix (ECM), simultaneously potentiated epithelial-mesenchymal transition (EMT), induced cancer stem cell markers (CD44 and EpCAM), enhanced mammosphere formation and intensified 3-dimentional invasion. Oncogenic SRC upregulated matrix metallopeptidases (MMPs) were assembled by invadopodia, acting as executive effectors for multi-step metastasis. ASPH-SRC signal guided multi-organ metastases (to lungs, liver, bone, spleen, lymph nodes, mesentery or colon) in immunocompromised mice. Malignant phenotypes induced by ASPH-SRC axis were reversed by the third-generation small molecule inhibitor (SMI) specifically against ß-hydroxylase activity of ASPH in pre-clinical models of metastatic breast cancer. Collectively, ASPH could activate ADAMs-SRC-MMPs cascades to promote breast cancer tumor progression and metastasis. ASPH could direct invadopodium construction as a biomechanical sensor and pro-metastatic outlet. ASPH-mediated cancer progression could be specifically/efficiently subverted by SMIs of ß-hydroxylase activity. Therefore, ASPH emerges as a therapeutic target for breast cancer.

Successful, Combined Long-term Treatment of Cerebral Candidiasis and Aspergillosis in a Liver Transplant Recipient: A Case Report.

Invasive fungal infections, of which the most common are candidiasis and aspergillosis, are among the most important and fatal complications in solid organ transplantation. They continue to be a significant cause of morbidity and mortality in patients with involvement of the central nervous system (CNS) because of the poor CNS penetration of antifungal medications. Voriconazole yields fungicidal drug concentrations in the CNS, but its use is limited in solid organ transplant patients because of its metabolic interactions with immunosuppression. Here we report a case of invasive fungal infection in the CNS after an emergency liver transplantation due to hepatitis B virus-related acute liver failure. The patient was managed successfully with a long-term conservative medical treatment.

Organelle dynamics of endothelial mitochondria in diabetic angiopathy.

Diabetes, a chronic non-communicable disease, has become one of the most serious and critical public health problems with increasing incidence trends. Chronic vascular complications are the major causes of disability and death in diabetic patients with endothelial dysfunction. Diabetes is intimately associated with endothelial mitochondrial dysfunction, indicated by increased oxidative stress, decreased biogenesis, increased DNA damage, and weakened autophagy in mitochondria. All these morphological and functional changes of mitochondria play important roles in diabetic endothelial dysfunction. Herein, we reviewed the roles and mechanisms of endothelial mitochondrial dysfunction, particularly mitochondrial dynamics in the vascular complications of diabetes and summarized the potential mitochondria-targeted therapies in diabetic vascular complications.

Upregulated mH2A1 serves as an unfavorable prognostic indicator and promotes the progress of hepatocellular carcinoma (HCC).

PURPOSE: To investigate the role and prognostic value of mH2A1 in the progression of hepatocellular carcinoma (HCC). METHODS: Basing on the Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) and GEO datasets, the gene expression of mH2A1 and relative clinical characteristics were analyzed to assess the prognostic significant of mH2A1 in HCC. The protein expression of mH2A1 was measured by immunohistochemistry. Stable cell lines and nude mice model were used to investigate the role of mH2A1 in the progression of HCC. RESULTS: In this study, using TCGA-LIHC data and HCC tissue microarray, we found that expression of mH2A1 was higher in tumor tissues than in adjacent normal tissues. These results were validated using the GEO database. Patients with high levels of mH2A1 were predicted to have larger tumor size and more advanced tumor stage and grade. Multivariate analysis revealed that increased mH2A1 expression was an independent prognostic risk factor of shorter overall survival (OS). Experimental results showed that elevated mH2A1 expression promoted the progression of HCC while reduced mH2A1 expression lead to opposite effects in vitro and in vivo. mH2A1 promoted the progression of HCC by regulating cell cycle via AKT. Dysregulated expression of mH2A1 was associated with its DNA methylation status. Two CpG sites (cg01466741 and cg02614129) were negatively correlated with mH2A1 expression. Notably, high methylation of both CpG sites was associated with better OS. CONCLUSION: Based on the above results, we concluded that upregulated mH2A1 in HCC promoted tumor progression and could serve as an unfavorable prognostic indicator.

ABCA8 is regulated by miR-374b-5p and inhibits proliferation and metastasis of hepatocellular carcinoma through the ERK/ZEB1 pathway.

BACKGROUND: ATP binding cassette subfamily A member 8 (ABCA8) belongs to the ATP binding cassette (ABC) transporter superfamily. ABCA8 is a transmembrane transporter responsible for the transport of organics, such as cholesterol, and drug efflux. Some members of the ABC subfamily, such as ABCA1, may inhibit cancer development. However, the mechanism of ABCA8 in the process of cancer activation is still ambiguous. METHODS: The expression of ABCA8 in human hepatocellular carcinoma (HCC) tissues and cell lines was examined using qPCR, immunoblotting, and immunohistochemical staining. The effects of ABCA8 on the proliferation and metastasis of HCC were examined using in vitro and in vivo functional tests. A luciferase reporter assay was performed to explore the binding between microRNA-374b-5p (miR-374b-5p) and the ABCA8 3'-untranslated region (UTR). RESULTS: ABCA8 was frequently down-regulated in HCC and this down-regulation was negatively correlated with prognosis. The overexpression of ABCA8 inhibited growth and metastasis in HCC, whereas the knockdown of ABCA8 exerted the antithetical effects both in vivo and in vitro. ABCA8 was down-regulated by miR-374b-5p; this down-regulation can induce epithelial transformation to mesenchyme via the ERK/ZEB1 signaling pathway and promote HCC progression. CONCLUSION: We exposed the prognostic value of ABCA8 in HCC, and illuminated a novel pathway in ABCA8-regulated inhibition of HCC tumorigenesis and metastasis. These findings may lead to a new targeted therapy for HCC through the regulation of ABCA8, and miR-374b-5p.

The protective role of DPP4 inhibitors in atherosclerosis.

Diabetes is a chronic non-communicable disease whose incidence continues to grow rapidly, and it is one of the most serious and critical public health problems. Diabetes complications, especially atherosclerosis-related chronic vascular complications, are a serious threat to human life and health. Growing evidence suggests that dipeptidyl peptidase 4 (DPP4) inhibitors, beyond their role in improving glycemic control, are helpful in ameliorating endothelial dysfunction in humans and animal models of T2DM. In fact, DPP4 inhibitors have been shown by successive studies to play a protective effect against vascular complications. On one hand, in addition to their hypoglycemic effects, DPP4 inhibitors participate in the control of atherosclerotic risk factors by regulating blood lipids and lowering blood pressure. On the other hand, DPP4 inhibitors exert anti-atherosclerotic effects directly through multiple mechanisms, including improving endothelial cell dysfunction, increasing circulating endothelial progenitor cell (EPCs) levels, regulating mononuclear macrophages and smooth muscle cells, inhibiting inflammation and oxidative stress and improving plaque instability. Herein, we review the beneficial roles of DPP4 inhibitors in atherosclerosis as detailed.