A Novel Prognostic Model for Patients with Primary Gastric Diffuse Large B-Cell Lymphoma.

Objectives: Primary gastric diffuse large B-cell lymphoma (PG-DLBCL) is a common phenotype of extranodal non-Hodgkin's lymphoma (NHL). This research aims to identify a model for predicting overall survival (OS) and cancer-specific survival (CSS) in PG-DLBCL. Methods: A total of 1716 patients diagnosed with PG-DLBCL between 1975 and 2017 were obtained from the SEER database and further randomly divided into the training and validating cohorts at a ratio of 7 : 3. Univariate and multivariate cox analyses were conducted to determine significant variables for the construction of nomogram. The performance of the model was then assessed by the concordance index (C-index), the calibration plot, and the area under the receiver operating characteristic (ROC) curve (AUC). Results: Multivariate analysis revealed that age, race, insurance status, Ann Arbor stage, marital status, chemotherapy, and radiation therapy all showed a significant association with OS and CSS. These characteristics were applied to build a nomogram. In the training cohort, the discrimination of nomogram for OS and CSS prediction was excellent (C-index = 0.764, 95% CI, 0.744-0.784 and C-index = 0.756, 95% CI, 0.732-0.780). The AUC of the nomogram for predicting 3- and 5-year OS was 0.779 and 0.784 and CSS was 0.765 and 0.772. Similar results were also observed in the internal validation set. Conclusions: We have successfully established a novel nomogram for predicting OS and CSS in PG-DLBCL patients with good accuracy, which can help physicians to quickly and accurately complete the evaluation of survival probability, risk stratification, and therapeutic strategy at diagnosis.

Relaxin-3 Ameliorates Diabetic Cardiomyopathy by Inhibiting Endoplasmic Reticulum Stress.

Background: This study is aimed at investigating whether relaxin-3 exhibits protective effects against cardiomyopathy in diabetic rats by suppressing ERS. Methods: Eighty male SD rats were randomly divided into two groups: controls (n = 20) and diabetes (n = 60). The streptozotocin-treated rats were randomly divided into three groups: diabetic group (DM), low-dose relaxin-3 group (0.2 µg/kg/d), and high-dose relaxin-3 group (2 µg/kg/d). The myocardial tissues and collagen fiber were observed by hematoxylin and eosin (H&E) and Masson staining. Serum brain natriuretic peptide (BNP), troponin (TNI), myoglobin, interleukin (IL-17), interleukin (IL)-1α, and tumor necrosis factor (TNF)-α were determined by ELISA. The protein expression of glucose regulatory protein 78 (GRP78) and C/EBP homologous protein (CHOP) in the heart tissue of each group was detected by Western blot analysis. Results: (1) HE and Masson staining indicated that relaxin-3 could attenuate myocardial lesions and myocardial collagen volume fraction. (2) BNP, TnI, and myoglobin in the DM group at four and eight weeks were significantly higher than in the controls (P < 0.01). The relaxin-3-treated groups showed significantly reduced serum BNP, TnI, and myoglobin levels compared with the DM group (P < 0.05). (3) IL-17, IL-1α, and TNF-α levels in the DM rats at 4 weeks were higher than in the controls (P < 0.05). Low or high dose of relaxin-3-treated groups showed reduced serum IL-17 and TNF-α levels compared with the DM group at four and eight weeks (P < 0.05). (4) CHOP and GRP78 protein expression was increased in the DM group at four and eight weeks compared with the controls (P < 0.01), and small and large doses of relaxin-3 significantly reduced GRP78 and CHOP protein expression. Conclusions: Exogenous relaxin-3 ameliorates diabetic cardiomyopathy by inhibiting ERS in diabetic rats.

Overlapping anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis with neuromyelitis optica spectrum disorders: a case report.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis can coexist with neuromyelitis optica spectrum disorder (NMOSD). Patients with overlapping anti-NMDAR encephalitis with positive NMDAR antibodies and aquaporin 4 immunoglobulin G (AQP4-IgG)-seropositive NMOSD are rare but should not be ignored. CASE PRESENTATION: This report describes a unique case of anti-NMDAR encephalitis coexisting with NMOSD. A 27-year-old male presented with blurred vision, cognitive impairment, psychosis, dysphagia, gait instability and urinary incontinence. Brain magnetic resonance imaging (MRI) showed abnormal signals in the right cerebellar hemisphere, temporal lobe, and corpus callosum. NMDAR antibodies were positive in the CSF. AQP4-IgG antibodies were positive in the serum. The patient's condition was stable following intravenous gamma globulin, corticosteroids, immunosuppressants and symptomatic treatments. CONCLUSIONS: This case provides further evidence for the occurrence of anti-NMDAR encephalitis overlapping NMOSD with AQP4-IgG-seropositive in a Chinese patient. However, the mechanisms underlying the occurrence of double-positive antibodies remain elusive.

Effect of Peptidylarginine Deiminase 4 on Endothelial Progenitor Cell Function in Peripheral Arterial Disease.

At present, the global prevalence of peripheral arterial disease is increasing year by year, and it has become a worldwide disease. Studies have shown that transplanting endothelial progenitor cells (EPCs) into ischemic tissues can improve the tissue ischemia, thereby having a therapeutic effect on peripheral arterial diseases. This indicates that EPCs play a therapeutic effect in peripheral arterial disease. Recent studies have shown that peptidylarginine deiminase (PAD) is involved in the regulation of epigenetics and its inhibitor Cl-amidine can improve endothelium-dependent vasodilation and significantly reduce the formation of arterial thrombosis. It can also play a role in hematopoietic stem cells that share the same origin with EPCs. Therefore, we speculate that PAD4 may also have an effect on EPCs through a similar mechanism, thereby participating in the damage and repair of peripheral arterial disease. Therefore, we first detected the expression of PAD4 in EPCs of peripheral arterial disease and detected changes in the number and function of endothelial progenitor cells in peripheral blood after injecting the PAD4 inhibitor Cl-amidine into mice. A mouse model of lower limb ischemia was established to explore the effect of PAD4 on the function of EPCs in peripheral arterial disease. The results show that PAD4 is highly expressed in peripheral arterial diseases and the PAD4 inhibitor Cl-amidine can increase the number of EPCs and can treat peripheral arterial diseases by improving the proliferation, migration, and vascularization of EPCs.

Catechin relieves hypoxia/reoxygenation-induced myocardial cell apoptosis via down-regulating lncRNA MIAT.

BACKGROUND: Catechin protects heart from myocardial ischaemia/reperfusion (MI/R) injury. However, whether catechin inhibits H/R-induced myocardial cell apoptosis is largely unknown. OBJECTIVE: This study aims to investigate the underlying mechanism of catechin in inhibiting the apoptosis of H/R-induced myocardial cells. METHODS: LncRNA MIAT expression was detected by qRT-PCR. Cell viability of H9C2 cells was detected using CCK-8 assay. The apoptosis of H9C2 cells was detected by flow cytometry. The interaction between CREB and MIAT promoter regions was confirmed by dual-luciferase reporter gene assay and ChIP assay. RESULTS: In MI/R rats, catechin improved heart function and down-regulated lncRNA MIAT expression in myocardial tissue. In H/R-induced H9C2 cells, catechin protected against cell apoptosis, and lncRNA MIAT overexpression attenuated this protective effect of catechin. We confirmed that transcription factor CREB could bind to MIAT promoter region, and catechin suppressed lncRNA MIAT expression through up-regulating CREB. Catechin improved mitochondrial function and relieved apoptosis through promoting Akt/Gsk-3ß activation. In addition, MIAT inhibited Akt/Gsk-3ß activation and promoted cell apoptosis in H/R-induced H9C2 cells. Finally, we found catechin promoted Akt/Gsk-3ß activation through inhibiting MIAT expression in H/R-induced H9C2 cells. CONCLUSION: Catechin relieved H/R-induced myocardial cell apoptosis through regulating CREB/lncRNA MIAT/Akt/Gsk-3ß pathway.

Crown ether-appended calix[2]triazolium[2]arene as a macrocyclic receptor for the recognition of the H2PO4- anion.

A crown ether-appended calix[2]triazolium[2]arene, which exhibits excellent selectivity for H2PO4- compared to other anions, has been designed and synthesized. The selectivity of the prepared receptor for H2PO4- is caused by the stabilization of H2PO4- by the neighboring triazolium hydrogen bond donors and crown ether hydrogen bond acceptors.

Inflammatory cytokines in cardiac pacing patients with atrial fibrillation and asymptomatic atrial fibrillation.

BACKGROUND: To investigate the changes of inflammatory cytokines in cardiac pacing patients with atrial fibrillation and asymptomatic atrial fibrillation and the effects of metoprolol on them. METHODS: A total of 92 cardiac pacing patients with atrial fibrillation and asymptomatic atrial fibrillation in our hospital from April 2015 to March 2017 were selected and randomly divided into the control group and the observation group, with 46 cases in each group. Three months after pacemaker implantation, the control group was treated with aspirin, the observation group was treated with metoprolol on the basis of aspirin, and the curative effects were compared between the two groups. After treatment, the heart rate, the frequency and duration of atrial fibrillation and the atrial fibrillation load were observed. P-wave dispersion (PD) and cardiac function of the two groups of patients at 6 months after treatment were compared. The changes of serum levels of tumor necrosis factor-α (TNF-α), high sensitive C-reactive protein (Hs-CRP) and interleukin-6 (IL-6) in patients were compared before treatment and at 1, 3 and 6 months after treatment. The quality of life of the two groups of patients was observed. RESULTS: After treatment, the effective rate of treatment in the observation group was significantly higher than that in the control group (P<0.05). After treatment, the average heart rate and atrial fibrillation load in the observation group were significantly improved compared with those in the control group, and the frequency and duration of atrial fibrillation were significantly lower than those in the control group (P<0.05). After treatment, the maximum P-wave duration (Pmax), the minimum P-wave duration (Pmin) and PD in the observation group were significantly lower than those in the control group (P<0.05). The left ventricular ejection fraction (LVEF) in the observation group was significantly higher than that in the control group, and the left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and E/A in the observation group were significantly lower than those in the control group (P<0.05). After treatment, the levels of TNF-α, Hs-CRP and IL-6 in the two groups of patients were decreased significantly, and those in the observation group were significantly lower than those in the control group (P<0.05). The quality of life score in the observation group was significantly higher than that in the control group (P<0.05). CONCLUSIONS: Metoprolol can effectively reduce the incidence of atrial fibrillation, atrial fibrillation loadand inflammatory cytokine levels in cardiac pacing patients with atrial fibrillation and asymptomatic atrial fibrillation, and improve cardiac function of the patients and their quality of life. It has an important clinical significance.

Role of microRNA-29b in angiotensin II-induced epithelial-mesenchymal transition in renal tubular epithelial cells.

Angiotensin II (Ang II) has been proven to induce epithelial-mesenchymal transition (EMT). The aim of the present study was to determine the role of microRNA-29b (miR-29b) during Ang II-induced EMT. For this purpose, we used spontaneously hypertensive rats (SHRs) and age-matched Wistar-Kyoto (WKY) rats. The levels of Ang II and its receptor in the kidneys of the SHRs are significantly higher than those in the age-matched WKY rats. As shown by RT-qPCR, the expression of miR-29b in the renal cortex was lower in the SHRs than in the WKY rats. For in vitro experiments, NRK-52E renal tubular epithelial cells were treated with 10(-7) M Ang II; we found that the expression of miR-29b was decreased in the cells treated with Ang II. In addition, transfection of the NRK-52E cells with miR-29b inhibitor led to the downregulation of miR-29b in these cells, and increased the expression of transforming growth factor (TGF)-ß, α-smooth muscle actin (α-SMA) and collagen I (Col I). Similar results were observed with the induction of Ang II expression in the NRK-52E cells. By contrast, the upregulation of miR-29b by transfection with miR-29b mimics inhibited the overexpression of these genes induced by Ang II. These results suggest that miR-29b plays an important role in Ang II-induced EMT.

Effect of nicotine on L-dopa-induced dyskinesia in animal models of Parkinson's disease: a systematic review and meta-analysis.

L-dopa-induced dyskinesias (LIDs) are abnormal involuntary movements (AIM) that develop with long-term L-dopa therapy for Parkinson's disease (PD). In this study, we used these tools to describe the efficacy of nicotine reduced LID in animal models of PD. Studies were identified by electronic searching of six online databases up to September of 2013 to identify preclinical trials involving nicotine for LID in animal model. Data were extracted for AIM compared with LID animals. Pre-specified subgroup analysis was carried out according to method of model, gender, anesthetic used, and species. Combined standardized mean difference (SMD) estimates and 95 % confidence intervals (CIs) were calculated using a random-effects model. Eleven studies involving 181 animals which described the effect of nicotine on LID were included in the meta-analysis. Nicotine was efficacious in reducing total AIM compared with control group (SMD -3.77, 95 % CI -5.30 to -2.23, P < 0.00001). Meanwhile, four studies showed certain effects of nicotine for improving the axial AIM (SMD -2.21, 95 % CI -4.17 to -0.24, P = 0.03); oral AIM and forelimb AIM were obvious improved in six studies in the nicotine group (SMD -3.00, 95 % CI -4.55 to -1.44, P = 0.0002; SMD -2.52, 95 % CI -3.52 to -1.53, P < 0.00001, respectively). We conclude that nicotine appears to have efficacy in animal models of LID. Large randomized clinical trials testing the effect of nicotine in PD patients with LID are warranted.