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Introduction This study is to investigate the effect of late-onset hemorrhagic cystitis (LOHC) on progression-free survival (PFS) of patients after haploidentical peripheral blood hematopoietic stem cell transplantation (haplo-PBSCT). Methods This retrospective study enrolled 74 patients with hematological malignancies treated with a myeloablative conditioning regimen and haplo-PBSCT. The effect of LOHC on PFS was studied in terms of HC occurrence, grade, disease type, duration, onset time, gender, and age. Results There were 28 patients with LOHC, and no case was with early-onset HC. The cumulative incidence of LOHC was 37.8% (95% CI: 26.9–48.7%). The 2-year expected PFS of 74 patients and 34 AML patients was not significantly different between LOHC patients and patients without HC (P > 0.05). Among 27 ALL patients, the 2-year expected PFS of LOHC patients was 75%, significantly higher than patients without HC (54.2%) (P < 0.05). The 2-year expected PFSs of patients with mild LOHC and severe LOHC were 69.8 and 77.8%, respectively (P > 0.05). Similarly, the onset time, duration, age, and gender of LOHC patients did not show significant effects on PFS (P > 0.05). Conclusions After haplo-PBSCT, LOHC has a significant effect on the PFS of ALL patients. The HC grade, duration, onset time, gender, and age have no significant effect on PFS.

Carp edema virus (CEV) is the pathogen of carp edema virus disease (CEVD), an emerging infectious disease with high morbidity and mortality worldwide. In the winter of 2016, a disease outbreak occurred in a koi pond in Chengdu, located in the southwest of China. The water temperature at that time was 11–13 °C. The clinical signs of the diseased koi were lethargy, unresponsiveness, enophthalmos, swollen gills, and hemorrhagic skin. Histopathological changes were observed in moribund fish, such as significant cell hyperplasia in the gill lamellae, and swelling and vacuolar degeneration in epithelial cells of the renal tubules and hepatocytes. Electron microscopy of renal tissues showed virions of a pox-like virus (200–235 nm diameter). The presence of specific 528 bp and 478 bp fragments was detected by nested PCR. An experimental infection demonstrated cumulative mortality of 15% (3/20) at a water temperature of 13 ± 2 °C. Furthermore, sequence analysis of the partial 4a genes showed that the CEV isolate (MG189372) in this study had 100% homology with a UK strain (KX254027). The evidence showed that the pathogen involved in this outbreak was CEV. To the best of our knowledge, this is the first report of carp disease caused by CEV at low temperature in China, demonstrating that CEV disease should be monitored in the cold season and at low temperatures. The findings are of profound significance to reducing the risk of CEVD outbreaks in carp aquaculture.

Introduction Severe hemorrhagic cystitis (HC) is still a common complication after allogeneic hematopoietic stem cell transplantation, which affects the quality of life of patients, and may even cause kidney failure. This study reports the clinical effect of adjuvant treatment of adipose-derived mesenchymal stem cells (ADSCs) on severe refractory HC after of reduced intensity conditioning haplotype high-dose peripheral blood hematopoietic stem cell transplantation (RIC-PBSCT) in one case. Patient concerns A 53-year-old female patient with acute myeloid leukemia (FLT3-ITD) at high risk received RIC-PBSCT. The patient was relieved with complete donor chimerism of 99.01%, and normal hemogram. However, the patient developed frequent urination, urgency, and dysuria with gross hematuria with blood clots and difficult urinating, especially at night and early in the morning. There were obvious hyperemia and bleeding points in the mucosa of the posterior wall of the bladder. Diagnosis The patient was diagnosed as delayed HC of degree IV. Interventions and outcomes The patient was treated with antiviral drugs, urine alkalization, and diuretic drugs for more than 1 month, but no significant effect was obtained. Thus, the patient was then given ADSCs (1 × 106 kg per kg of body weight, infused once a week for a total of 3 infusions). Symptoms of frequent urination, urgency, and dysuria that happened during the first infusion were improved, and blood clots in the urine were also reduced. After the third infusion, HC symptoms disappeared, the red blood cells were normal, and there was no fever, chills, low infusion blood pressure, or rash. The patient's HC was cured. During follow-up, HC recurrence was not observed. Conclusion ADSCs adjuvant treatment of relapsed and refractory severe HC is safe and reliable with good clinical efficacy. It shows certain clinical application value, which however requires more clinical cases to further verify this.

Background: Paired related homeobox 1 (PRRX1) and zinc finger E-box binding homeobox 1 (ZEB1) have been observed to play a vital role in the epithelial-mesenchymal transition (EMT) process in different types of cancer. The microvessel density (MVD) is the most common indicator used to quantify angiogenesis. This study aimed to investigate expression of PRRX1 and ZEB1 in non-small cell lung cancer (NSCLC) and to explore associations between these factors and tumor prognosis, EMT markers and angiogenesis. Methods: Data for a total of 111 surgically resected NSCLC cases from January 2013 to December 2014 were collected. We used an immunohistochemical method to detect expression levels of PRRX1, ZEB1, and E-cadherin, and to assess MVD (marked by CD34 staining). SPSS 26.0 was employed to evaluate the connection between these factors and clinical and histopathological features, overall survival (OS) and tumor angiogenesis. Results: PRRX1 expression was obviously lower in tumor samples than in control samples. Low expression of PRRX1, which was more common in the high-MVD group than in the low-MVD group (P = .009), correlated positively with E-cadherin expression (P

Dongzheng Li,1 Ruixue Yang,2 Liu Yang,1 Dongfeng Wang,1 Xin Zhou,1 Yan Sun11Department of General Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, Jiangsu 210009, People’s Republic of China; 2Department of Paediatrics, Taikang Xianlin Drum Tower Hospital, Nanjing, Jiangsu 210046, People’s Republic of ChinaBackground: Circular RNAs (circRNAs) and microRNAs (miRNAs) play key roles in the development of human cancers. CircANKS1B has been reported to be increased in breast cancer.Methods: Real-time polymerase chain reaction (real-time PCR) assay was used to measure expressions of circANKS1B, ANKS1B, and FOXM1. Western blot assay was employed to examine the protein level of FOXM1 and Slug. The abilities of cell migration and invasion were measured by wound-healing and transwell assays. The interaction between circANKS1B and miR-149 was confirmed by site-directed mutagenesis and luciferase assays.Results: The expression of circANKS1B was up-regulated in colorectal cancer tissues and cells. Additionally, circANKS1B increased the expression of FOXM1. Furthermore, the enhancement of CRC cell migration and invasion by circANKS1B was dependent on FOXM1. However, previous studies have shown that miR-149 can directly target FOXM1 and act as tumor suppressor in CRC. Consequently, our results showed that miR-149 could directly bind to circANKS1B and FOXM1. The inhibition of circANKS1B could reduce FOXM1 and Slug protein levels, thus suppressing CRC cell migration and invasion.Conclusion: Taken together, circANKS1B promotes colorectal cancer cell migration and invasion by acting as a molecular sponge of miR-149 to modulate FOXM1 and Slug protein levels.Keywords: circANKS1B, cell invasion, miR-149, FOXM1, colorectal cancer

Angiogenic factor with G-patch and FHA domain 1 (AGGF1) is a newly initiator of angiogenesis. Forkhead box C2 (FOXC2) that is a member of the winged spiral transcription factor family plays an important role in epithelial-mesenchymal transition (EMT). Epithelial-cadherin (E-cad) that is an adhesion molecule is also involved in EMT. The purpose of this study is to investigate the expression of AGGF1, FOXC2, and E-cad in esophageal squamous cell carcinoma (ESCC) and their clinical significance. Immunohistochemistry was performed to investigate the expression of AGGF1, FOXC2, and E-cad in 170 ESCC specimens and corresponding normal esophageal mucosa tissues. Follow-up data was also collected. The positive rates of AGGF1 and FOXC2 expression were significantly higher in ESCC group when compared with the control group; the positive rate of E-cad expression was significantly lower in ESCC group when compared with the control group. Positive rates of AGGF1, FOXC2, and E-cad expression were significantly associated with grades of differentiation, tumor grades, lymph node metastasis stages, as well as tumor-node-metastasis stages. Kaplan–Meier analysis demonstrated that positive expression of AGGF1 or FOXC2 for ESCC patients had significantly unfavorably overall survival time when compared with patients with negative expression of AGGF1 or FOXC2; and positive expression of E-cad for ESCC patients had significantly longer overall survival time when compared with patients with negative expression of E-cad. Multivariate analysis indicated that AGGF1, FOXC2, and E-cad expression and tumor-node-metastasis stages were postoperative independent prognostic factors for ESCC patients. AGGF1, FOXC2, and E-cad may be considered promising biomarkers of ESCC patients’ prognosis.

Vasculogenic mimicry (VM) is a new blood supply style in tumors and has long been treated as a useful factor in malignant tumor metastasis and prognosis. Notch4 (a marker of Notch signaling pathway receptors), DLL4 (a marker of Notch signaling pathway ligands) and KAI1/CD82 (a suppressor gene of tumor metastasis) are all effective predictive factors for tumor metastasis. In this study, we analyzed correlations among VM, Notch4, DLL4, and KAI1/CD82 in non-small cell lung cancer (NSCLC), and their respective associations with patients’ clinicopathological parameters and survival rate in NSCLC. Positive rates of VM, Notch4, DLL4, and KAI1/CD82 in 189 whole NSCLC specimens were detected by histochemical and immunohistochemical staining. Moreover, patients’ clinicopathological information was also collected. Positive rates of VM, Notch4, and DLL4 were significantly higher, and levels of KAI1/CD82 were significantly lower in NSCLC than in normal lung tissues. Positive rates of VM, Notch4, and DLL4 were positively associated with tumor size, lymph node metastasis (LNM), distant metastasis (DM) and tumor-node-metastasis (TNM) stage, and inversely with patients, overall survival (OS) time and positive rate of DLL4 were positively associated with tumor grade. Levels of KAI1/CD82 were negatively associated with tumor size, LNM, DM, and TNM stage. The KAI1/CD82+ subgroup had significantly longer OS time than did the KAI1/CD82- subgroup. In multivariate analysis, high VM, Notch4, DLL4 levels, tumor size, LNM, DM, TNM stage, and low KAI1/CD82 levels were potential to be independent prognostic factors for overall survival time (OST) in NSCLC patients. VM and the expression of Notch4, DLL4, and KAI1/CD82 represent promising markers for tumor metastasis and prognosis, and maybe potential therapeutic targets for NSCLC.

Andrographolide (Andro), a major bioactive component obtained from Andrographis paniculata Nees, has exerted wide antioxidant as well as cytoprotective properties. However, whether Andro treatment could retard the progress of diabetic cardiomyopathy (DCM) remains unknown. In this study, we evaluated the effects of Andro against diabetes-induced myocardial dysfunction and explored the underlying mechanism in STZ-induced diabetic mice. As a result, treatment with Andro dose dependently suppressed cardiac inflammation and oxidative stress, accompanied by decreasing cardiac apoptosis, which subsequently ameliorated cardiac fibrosis and cardiac hypertrophy. Further, Andro blocked hyperglycemia-triggered reactive oxygen species (ROS) generation by suppressing NADPH oxidase (NOX) activation and augmenting nuclear factor erythroid 2-related factor 2 (Nrf2) expression both in vitro and in vivo. Our results suggest that the cardioprotective effects afforded by Andro treatment involve the modulation of NOX/Nrf2-mediated oxidative stress and NF-κB-mediated inflammation. The present study unravels the therapeutic potential of Andro in the treatment of DCM by attenuating oxidative stress, inflammation, and apoptosis.

Peptidyl-prolyl isomerase Pin1 has been reported to be associated with endothelial dysfunction. However, the role of smooth muscle Pin1 in the vascular system remains unclear. Here, we examined the potential function of Pin1 in smooth muscle cells (SMCs) and its contribution to abdominal aortic aneurysm (AAA) pathogenesis. The level of Pin1 expression was found to be elevated in human AAA tissues and mainly localized to SMCs. We constructed smooth muscle-specific Pin1 knockout mice to explore the role of this protein in AAA formation and to elucidate the underlying mechanisms. AAA formation and elastin degradation were hindered by Pin1 depletion in the angiotensin II-induced mouse model. Pin1 depletion reversed the angiotensin II-induced pro-inflammatory and synthetic SMC phenotype switching via the nuclear factor (NF)-κB p65/Klf4 axis. Moreover, Pin1 depletion inhibited the angiotensin II-induced matrix metalloprotease activities. Mechanically, Pin1 deficiency destabilized NF-κB p65 by promoting its polyubiquitylation. Further, we found STAT1/3 bound to the Pin1 promoter, revealing that activation of STAT1/3 was responsible for the increased expression of Pin1 under angiotensin II stimulation. Thus, these results suggest that Pin1 regulates pro-inflammatory and synthetic SMC phenotype switching and could be a novel therapeutic target to limit AAA pathogenesis.

Vasculogenic mimicry (VM) involves a tubular structure with a basement membrane that is similar to and communicates with vessels but functions independent of blood vessels to nourish tumor cells, promote tumor progression, invasion, and metastasis, with reduced 5-year survival rates. Tumor cell proliferation, invasion, and metastasis are promoted by the epithelial-mesenchymal transition (EMT). Paired-related homeobox 1 (PRRX1), a newly discovered EMT inducer, has been shown to correlate with metastasis and prognosis in diverse cancer types. Cancerous inhibitor of protein phosphatase 2A (CIP2A) was initially recognized as an oncoprotein. In this study, we aimed to investigate the expression and clinical significance of the EMT markers PRRX1, CIP2A and VM in clear cell renal cell carcinoma (CCRCC) and their respective associations with clinicopathological parameters and survival. Expression of PRRX1, CIP2A and VM in whole CCRCC tissues from 110 patients was analyzed by immunohistochemical and histochemical staining. Fisher's exact test or the chi square test was used to assess associations with positive or negative staining of these markers and clinicopathological characteristics. Positive expression of CIP2A and VM presence was significantly higher and that of PRRX1 was significantly lower in CCRCC tissues than in corresponding normal tissues. Furthermore, positive expression of CIP2A and VM was significantly associated with tumor grade, size, lymph node metastasis (LNM) stage, and tumor node metastasis (TNM) stage and inversely associated with overall survival time (OST). Moreover, levels of PRRX1 were negatively associated with tumor grade, size, LNM stage, and TNM stage. The PRRX1 subgroup had a significantly longer OST time than did the PRRX1 subgroup. In multivariate analysis, high VM and CIP2A, tumor grade, LNM stage, TNM stage, and low PRRX1 levels were identified as potential independent prognostic factors for OST in CCRCC patients. VM and expression of CIP2A and PRRX1 represent promising biomarkers for metastasis and prognosis and potential therapeutic targets in CCRCC.

Vascular remodeling is closely related to hypertension, atherosclerosis, and restenosis after PCI. Considerable evidence indicates that the activation and proliferation of adventitial fibroblasts play key roles in vessel injury. The inflammatory response and high expression of connexins contribute to adventitial remodeling. Therefore, reducing inflammation reaction and connexins expression in adventitia may become a new target to prevent vascular remodeling. Yiqihuoxuejiedu formula, composed of TCM therapeutic principle of supplementing qi, activating blood and detoxification, can inhibit restenosis after intimal injury. To further investigate the effect of Yiqihuoxuejiedu formula on inflammation and connexins, we established a carotid artery injury model. In model rats, hyperplasia in the intima was mild but obvious in the adventitia; CRP heightened; expressions of MCP-1, CD68, and Cx43 increased. Yiqihuoxuejiedu formula relieved intimal hyperplasia and adventitial area, obviously diminished the expressions of CD68 and Cx43 in the adventitia, and reduced CRP but did not lower MCP-1. These results indicated that Yiqihuoxuejiedu formula inhibited vascular remodeling especially adventitial hyperplasia by reducing the inflammation reaction including lowering macrophages infiltration and systemic nonspecific inflammatory response and also restraining gap junction connexins leading to less communication among cells. This study provides new ideas and methods for the prevention and treatment of vascular remodeling.