[A clinical research report on the pathophysiological characteristics of exercise in patients with mitral regurgitation].

Objective: Cardiopulmonary exercise testing (CPET) was used to investigate the exercise pathophysiology of mitral regurgitation. Methods: 26 patients with moderate and severe mitral regurgitation who completed standardized extreme exercise CPET under strict quality control after signing informed consent since 2016, and 11 normal subjects in the same period as the control group. The core indexes of CPET were analyzed and calculated according to the standard method and compared with normal subjects for intergroup statistical independent sample t-test. At the same time, the patients with heart failure and exercise oscillation breathing (OB) were divided into two subgroups: 11 cases without heart failure, 15 cases with heart failure, 8 cases with non-OB and 18 cases with OB, and their similarities and differences were compared between each subgroup. Results: The core indexes of CPET, such as peak oxygen uptake (85.60 ±9.06)%pred and anaerobic threshold (AT, (87.59 ±15.38)%pred) were normal. The peak oxygen uptake of CPET in patients with mitral regurgitation was (48.15 ±12.11)%pred, peak oxygen pulse was (66.57 ±12.20)%pred, AT was (56.75 ±11.50)%pred, oxygen uptake efficiency plateau was (88.24 ±16.42)%pred , lowest value of carbon dioxide ventilatory efficiency was (125.89 ±27.05)%pred and slope of carbon dioxide ventilatory efficiency was (128.31 ±31.68)%pred. Among them, only oxygen uptake efficiency plateau (OUEP) was normal and low, and the other indexes were significantly abnormal. There were significant differences between the patients and the control group (P<0.01). There was no significant difference between the non-OB group and the OB group, but there was significant difference between the non-OB group and the control group (P<0.05). There was no significant difference between the non-heart failure group and the heart failure group, but there was significant difference between the non-heart failure group and the control group. Conclusion: All the core indexes of cardiopulmonary exercise are significantly abnormal in patients with mitral regurgitation who are significantly lower than those in normal subjects except for the low effectiveness of oxygen ventilation. And with or without heart failure and OB did not affect the cardiopulmonary function.

High preoperative plasma fibrinogen and serum albumin score is associated with poor survival in operable esophageal squamous cell carcinoma.

This study was performed to investigate the prognostic significance of a cumulative score based on the preoperative plasma fibrinogen and serum albumin (FA score) in operable esophageal squamous cell carcinoma (ESCC). Clinicopathologic characteristics, preoperative fibrinogen, and albumin concentrations were retrospectively reviewed in patients who underwent transthoracic esophagectomy. The optimal cutoff value was defined as 4.0 g/L for fibrinogen according to previous studies and as 41.0 g/L for albumin for the lower quartile. Subjects with elevated fibrinogen and decreased albumin levels were allocated a score of 2, those with only one of these two abnormalities were assigned a score of 1, and those with neither of the abnormalities were allocated a score of 0. The preoperative FA score was significantly associated with tumor length, depth of invasion, lymph node involvement, tumor-node-metastasis (TNM) stage, and the modified Glasgow Prognostic Score (mGPS). No significant differences in age, gender, tumor location, degree of differentiation, smoking or alcohol consumption were found between groups. Univariate survival analysis revealed that high preoperative FA score (1/2) was significantly associated with unfavorable disease-free survival (DFS) [hazard ratio (HR), 1.675; 95% confidence interval (CI), 1.278-2.195; P < 0.001] and overall survival (OS) (HR, 1.685; 95% CI, 1.268-2.239; P < 0.001). Furthermore, it remained an independent prognostic indicator for both DFS (HR, 1.394; 95% CI, 1.035-1.879; P = 0.029) and OS (HR, 1.369; 95% CI, 1.010-1.878; P = 0.048) in multivariable Cox regression analysis. A high preoperative FA score could significantly predict impaired long-term survival for ESCC patients who underwent transthoracic esophagectomy.

Silencing of perilipin by short hairpin RNA inhibits proliferation and induces apoptosis in liposarcoma cells.

Previous studies have identified that perilipin-1 (PLIN1) is a highly specific marker for liposarcoma. However, its functions have yet to be fully elucidated. The aim of the present study was to investigate the potential role of PLIN1 in the proliferation, migration and apoptosis of liposarcoma cells. Short hairpin RNA was designed to inhibit PLIN1 levels. Cell proliferation was monitored by Cell Counting Kit­8 assay and cell migration determined by wound healing assay. Flow cytometry was performed to assess the cell cycle distributions and apoptosis in liposarcoma cells. The results demonstrated that the expression of PLIN1 was significantly upregulated in liposarcoma tumor tissues compared with normal adipose tissues. Silencing of PLIN1 by short hairpin RNA significantly inhibited proliferation and migration and induced G1 phase cell cycle arrest and apoptosis in liposarcoma cell lines. It was identified that PLIN1 serves a crucial role in the pathogenesis and progression of liposarcoma and may be a potential therapeutic target for its clinical management.

Trastuzumab modified silica nanoparticles loaded with doxorubicin for targeted and synergic therapy of breast cancer.

Untargeted delivery as well as low efficacy are two main obstacles for effective breast cancer therapy. Here in this study, we surface modified silica nanoparticles (SLN) with Trastuzumab (Tra) to construct a tumor-targeting carrier (Tra-SLN) for specific drug delivery to human epidermal growth factor receptor 2 (HER2) overexpressing breast cancer cells. In addition, Tra-SLN could also loaded with broad-spectrum anticancer drug doxorubicin (DOX) to finally construct a drug delivery system (DDS) capable of co-delivering Tra and DOX (Tra-SLN/DOX). Our results demonstrated that the as-prepared Tra-SLN/DOX was nanoscale particles with spheroid appearance which showed preferable stability in physiological environments. In addition, the Tra-SLN/DOX could specifically target to HER2 overexpressed MCF-7 cells. Both in vitro and in vivo experiments revealed that the Tra-SLN/DOX exerted enhanced anticancer efficacy when compared with Tra or DOX alone. It was suggested that Tra-SLN/DOX might be a promising platform for enhanced therapy of breast cancer.

A novel functional polymorphism of GFAP decrease glioblastoma susceptibility through inhibiting the binding of miR-139.

Glioblastoma (GBM) is the most commonly diagnosed solid tumor outside the central nervous system. However, genetic factors underlying GBM remain largely unclear. Previous studies indicated that Glial fibrillary acidic protein (GFAP) might play an important role in the aggressiveness of GBM and also contributed to its poor overall survival. The present study aims to test (1) the associations between GFAP single nucleotide polymorphisms (SNPs) and GBM cells chemoresistance and metastasis, and (2) the molecular mechanism accounting for their effects. Four tagging SNPs of GFAP were initially genotyped in 667 subjects and the significant SNP was further analyzed via online bioinformatical tools. SNP rs11558961 was found to be significantly associated with GBM susceptibility. It was predicted to influence microRNA(miR)-139 binding to 3'UTR of GFAP gene. In functional experiments, we found that cells transfected with rs11558961 G-allele constructs had lower baseline luciferase activities and were more responsive to miR-139 changes, compared to C-allele constructs. Moreover, rs11558961 C>G variant reduced the chemoresistance of GBM cells and migration capability. In conclusion, rs11558961 might influence the chemoresistance and progression of GBM cells via promoting the binding of miR-139, ultimately decrease the susceptibility of GBM. This investigation will shed light on the optimizing for clinical trial design and individualizing of therapeutic plans.

Protein Regulator of Cytokinesis PRC1 Confers Chemoresistance and Predicts an Unfavorable Postoperative Survival of Hepatocellular Carcinoma Patients.

Background: PRC1, a microtubules(MTs)-associated protein, is essential in the mitosis and cell cycle regulation. It has been recently linked to chemoresistance and tumorigenesis. The current study sought to explore the role of PRC1 on chemoresistance and postoperative prognosis of hepatocellular carcinoma(HCC). Methods: PRC1 was transfected into HCC cells to detect its effects of chemoresistance to 5-fluorouracil in vitro and in vivo. This study also investigated the impact of PRC1 on 5-FU-induced G2/M phase arrest and the potential molecular mechanism. Surgical specimens from HCC patients were examined immunohistochemically for PRC1 expression. Results: Ectopic expression of PRC1 significantly increased the chemoresistance, promoted the tumor growth and abrogated 5-FU-induced G2/M phase arrest via p21/p27-pRBs pathway. In clinical specimens, high expression of PRC1(immunostaining score≥3) in HCC cells predicted an unfavorable postoperative survival of HCC patients(P=0.019), especially for whom received postoperative chemotherapy(P=0.002). In multivariate Cox analyses, high PRC1 expression significantly predicted an unfavorable postoperative prognosis, not dependent of TNM stage. Conclusion: High PRC1 expression in HCC cells increased chemoresistance, attenuated 5-FU-induced apoptosis, abrogated 5-FU-induced G2/M phase arrest, and predicts an unfavorable survival, especially for the patients who received chemotherapy. PRC1 might be a novel prognostic and predictive marker and therapeutic target for HCC patients.

Extraventricular neurocytoma of the sellar region: case report and literature review.

INTRODUCTION: The extraventricular neurocytoma of the sellar region (EVNSR) is a rare disease, it is difficult to make exact diagnosis of and operate on patients. Retrospectively analysed the clinical manifestations, image features, therapy methods and outcomes among patients with EVNSR, to investigate the epidemiological characteristics, image features, diagnosis, treatment and prognosis. CASE DESCRIPTION: A 25-year-old man man with 7-month worsening vision of left eye, was confirmed EVNSR after subtotally resection from the neurosurgical department of Deji hospital. DISCUSSION AND EVALUATION: Nine cases of EVNSR were reported from this article and elsewhere. Ages of these patients were ranging from 25 to 66 (with an average of 45.67). The male-female ratio was 1-2. All EVNSR patients had visual damage. Images showed the tumors were in the sellar and suprasellar regions. Preoperatively, all patients were misdiagnosed as other diseases: such as pituitary tumor, craniopharyngioma, and meningioma. For tumor removal treatment, five patients received transpterional approach, one received subfrontal approach and three received transnostril-transsphenoidal approach. EVNSR was confirmed by pathological tests. The tumor was completely removed in one patient. During the 12-24 month postoperative follow up period, the recurrence or metastasis of the tumor was found in two patients. CONCLUSIONS: EVNSR is a rare disease. It occurs mostly in middle-aged women. EVNSR is likely to be misdiagnosed as pituitary adenoma preoperatively. The histological examination would help confirm the diagnosis. Using transpterional approach to remove tumor will help the prognosis, especially among patients with normal pituitary function. Both postoperative radiotherapy and long-term follow-up are recommended.

Thrombin Maybe Plays an Important Role in MK Differentiation into Platelets.

OBJECTIVES: After development and differentiation, megakaryocytes (MKs) can produce platelets. As is well known, thrombopoietin (TPO) can induce MKs to differentiate. The effect of thrombin on MKs differentiation is not clear. In this study, we used a human megakaryoblastic leukemia cell line (Meg-01) to assess the effect of thrombin on MKs differentiation. METHODS: In order to interrogate the role of thrombin in Meg-01 cells differentiation, the changes of morphology, cellular function, and expression of diverse factors were analyzed. RESULTS: The results show that thrombin suppresses Meg-01 cells proliferation and induces apoptosis and cell cycle arrest. Thrombin upregulates the expression of CD41b, which is one of the most important MK markers. Globin transcription factor 1 (GATA-1), an important transcriptional regulator, controls MK development and maturation. The expression of GATA-1 is also upregulated by thrombin in Meg-01 cells. The expression of B-cell lymphoma 2 (Bcl-2), an apoptosis-inhibitory protein, is downregulated by thrombin. Phosphorylated protein kinase B (p-AKT) and phosphorylated extracellular signal-regulated kinase (p-ERK) were upregulated by thrombin in Meg-01 cells. All the results are consistent with Meg-01 cells treated with TPO. DISCUSSION AND CONCLUSION: In conclusion, all these data indicate that thrombin maybe plays an important role in MK differentiation into platelets. However, whether the platelet-like particles are certainly platelets remains unknown.

Multicenter study of creatinine- and/or cystatin C-based equations for estimation of glomerular filtration rates in Chinese patients with chronic kidney disease.

OBJECTIVE: To establish equations for the estimation of glomerular filtration rates (eGFRs) based on serum creatinine (SCr) and/or serum cystatin C (SCysC) in Chinese patients with chronic kidney disease (CKD), and to compare the new equations with both the reference GFR (rGFR) and the literature equations to evaluate their applicability. METHODS: The 788 Chinese CKD patients were randomly divided into two groups, the training group and the testing group, to establish new eGFR-formulas based on serum CysC and to validate the established formulas, respectively. (99m)Tc-DTPA clearance (as the rGFR), serum Cr, and serum CysC were determined for all patients, and GFR was calculated using the Cockcroft-Gault equation (eGFR1), the MDRD formula (eGFR2), the CKD-EPI formulas (eGFR3, eGFR4), and the Chinese eGFR Investigation Collaboration formulas (eGFR5, eGFR6). The accuracy of each eGFR was compared with the rGFR. RESULTS: The training and testing groups' mean GFRs were 50.84±31.36 mL/min/1.73 m(2) and 54.16±29.45 mL/min/1.73 m(2), respectively. The two newly developed eGFR formulas were fitted using iterative computation: [Formula: see text] and [Formula: see text]. Significant correlation was observed between each eGFR and the rGFR. However, proportional errors and constant errors were observed between rGFR and eGFR1, eGFR2, eGFR4, eGFR5 or eGFR6, and constant errors were observed between eGFR3 and rGFR, as revealed by the Passing & Bablok plot analysis. The Bland-Altman analysis illustrated that the 95% limits of agreement of all equations exceeded the previously accepted limits of <60 mL/min •1.73 m(2), except the equations of eGFR7 and eGFR8. CONCLUSION: The newly developed formulas, eGFR7 and eGFR8, provide precise and accurate GFR estimation using serum CysC detection alone or in combination with serum Cr detection. Differences in detection methods should be carefully considered when choosing literature eGFR equations to avoid misdiagnosis and mistreatment.

The effects of hepatitis C virus non-structural protein 3 on cell growth mediated by extracellular signal-related kinase cascades in human hepatocytes in vitro.

Hepatitis C virus (HCV) infection has become a severe health problem worldwide. The viral proteins are believed to be among the most important factors that contribute to HCV mediated pathogenesis. Accumulated evidence demonstrating that HCV non-structural protein 3 (NS3) possesses oncogenic potential, and is involved in the regulation of cell proliferation has been documented. In this study, we emphasized the effect of HCV NS3 protein on cell proliferation in the immortally normal hepatocyte QSG7701 cells. The cell line transfected with plasmid expressing NS3 protein showed enhanced cell growth, extracellular signal-related kinase (ERK) activation, DNA binding activities of transcription factors of activator protein 1 (AP-1) and NF-kappaB, and cyclin D1 overexpression, but without activation of Jun amino-terminal kinase or p38. Pre-treatment of NS3 protein expressing cells with ERK inhibitor, PD98059, blocked the activation of AP-1 and NF-kappaB, and inhibited cyclin D1 expression and cell proliferation. The results suggest that NS3-mediated cell growth occurs through activation of ERK/AP-1 and NF-kappaB/cyclin D1 cascades.

[Cross-talk between ERK and NF-kappaB signal transduction pathways in the hepatocytes expressing hepatitis C virus nonstructural protein 3].

OBJECTIVE: To explore the cross-talk between extracellular signal-regulated kinase (ERK) and nuclear factor (NF-kappaB) signal transduction pathways in the hepatocytes expressing hepatitis C virus nonstructural protein 3 (HCV NS3). METHODS: A cell line QSG7701/NS3, which stably expressed HCV NS3 protein, was constructed by transfecting plasmid pcDNA3.1-NS3 into a human immortalized hepatocyte line QSG7701. Before and after QSG7701/NS3 cells were treated by MEK inhibitor PD98059, the phosphorylation level of ERK and the expression of cyclin D1 protein were detected by Western blot; the DNA binding activities of activator protein 1 (AP-1) and NF-kappaB were evaluated with electrophoretic mobility shift assay (EMSA). Cell cycles were measured by flow cytometry (FCM); the effects of PD98059 on the cell proliferation were determined by MTT assay. RESULTS: HCV NS3 protein could up-regulate the phosphorylation of ERK and the expression level of cyclin D1 in QSG7701 cells. PD98059 could inhibit the cell proliferation mediated by HCV NS3 protein, down-regulate the activities of AP-1 and NF-kappaB, and suppress the expression of cyclin D1. CONCLUSION: The inhibition of ERK can suppress the DNA binding activity of NF-kappaB and the cell proliferation mediated by HCV NS3 protein in a dose-dependent manner. There may be a cross-talk between ERK and NF-kappaB signal transduction pathways, which may exert synergistic action on the proliferation and malignant transformation of hepatocytes.