Prognostic values of pretreatment neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in endometrial cancer: a systematic review and meta-analysis.

PURPOSE: Elevated inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), have been identified as poor predictors of survival in several malignancies. This meta-analysis was performed to quantify the effect of pretreatment NLR and PLR on the survival of patients with endometrial cancer (EC). METHODS: This review systematically searched for relevant publications in databases of PubMed, Embase, and the Cochrane Library. Pooled hazard ratios (pHRs) with 95% confidence intervals (95% CIs) were determined and used to explore the association between inflammatory markers and overall survival (OS) and disease-free survival (DFS) in a random-effects model. Subgroup analysis, sensitivity analysis, and publication bias were also conducted in this meta-analysis. RESULTS: Nine articles comprising 3390 patients were included. NLR higher than the cutoff was associated with a shorter OS (pHR = 2.22, 95% CI 1.77-2.78) and poorer PFS (pHR = 1.81, 95% CI 1.35-2.41). Patients with elevated PLR had high risk of decreased OS (pHR = 1.99, 95% CI = 1.51-2.61) and unfavorable PFS (pHR = 2.02, 95% CI 1.45-2.80). CONCLUSIONS: Elevated NLR and PLR during pretreatment are biomarkers of poor prognosis in patients with EC.

Anticancer effect of berberine based on experimental animal models of various cancers: a systematic review and meta-analysis.

BACKGROUND: Numerous studies have explored the anti-tumor effect of berberine (BBR), but little clinical evidence guides the use of BBR in cancer patients. OBJECTIVES: Our aim was to investigate the impact of BBR on various cancers in healthy animals to promote the transformation from bench to bed. SEARCH METHODS: PubMed, Embase, Springer, and Cochrane databases were searched from January 2000 to October 2018 for relevant articles. SELECTION CRITERIA: Only published studies focusing on the relationship between BBR and various cancers in vivo were qualified. Two review authors independently assessed the risk of bias for each study, and any disagreement was resolved by discussion or by involving a third assessor. RESULTS: A total of 26 studies from 2000 to 2018, focusing on various cancer types, including breast cancer, liver cancer, colorectal cancer, nasopharyngeal carcinoma, lung cancer, gastric cancer, neuroepithelial cancer, endometrial carcinoma, esophageal cancer, tongue cancer, cholangiocarcinoma, and sarcoma were included. Overall, BBR reduced tumor volume (SMD =3.72, 95% CI: 2.89, 4.56, Z = 8.73, p < 0.00001) and tumor weight (SMD =2.35, 95% CI: 1.51, 3.19, Z = 5.50, p < 0.00001) in a linear The dose-response relationship (Pearson r = - 0.6717, p < 0.0001 in tumor volume analysis; Pearson r = - 0.7704, p < 0.0005 in tumor weight analysis). BBR inhibited angiogenesis in tumor tissues (SMD = 4.29, 95% CI: 2.14, 6.44, Z = 3.92, p < 0.00001), but it had no significant effect on the body weight of experimental animals (SMD = 0.11, 95% CI: - 0.70, 0.92, Z = 0.27, p = 0.78). Publication bias was not detected. CONCLUSION: BBR exerted anti-tumor effects in a variety of tumors in vivo, especially breast cancer and lung cancer, and the evidence was still insufficient in colorectal cancer and gastric cancer.

2-Deoxy-D-Glucose Exhibits Anti-seizure Effects by Mediating the Netrin-G1-KATP Signaling Pathway in Epilepsy.

Epilepsy is a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures. The glycolytic inhibitor 2-deoxy-D-glucose (2-DG) has been reported to exert antiepileptic effects by upregulating KATP subunits (kir6.1 and kir6.2). We evaluated whether 2-DG exhibits anti-seizure effect by mediating the netrin-G1-KATP signaling pathway in epilepsy. In a mouse epilepsy model induced by lithium chloride-pilocarpine, 2-DG intervention increased the mRNA and protein expression levels of kir6.1 and kir6.2, and these increases were significantly reversed after knocking down netrin-G1 expression. Similarly, in cultured neurons with a magnesium-free medium, we found that the frequency of spontaneous postsynaptic potentials (SP) was increased, and in the meanwhile, expression levels of kir6.1 and kir6.2 were increased after pretreatment with 2DG. These effects were remarkably reversed after knocking down netrin-G1. Thus, our findings show that 2DG exhibits anti-seizure effects through the netrin-G1-KATP signaling pathway.

Mortality of site-specific cancer in patients with schizophrenia: a systematic review and meta-analysis.

BACKGROUND: Numerous studies have reported contradicting results on the relationship between cancer mortality and schizophrenia. Our aim is to quantify the mortality rate of common site-specific cancers among patients with schizophrenia and to synthesize the available research evidence. METHODS: We performed a systemic search of the PubMed, EMBASE and Web of Science databases. Studies reporting the mortality rate of different cancer in patients with schizophrenia were included. A random-effects model was applied to calculate the pooled relative risks (RRs) with 95% confidence intervals (95%CIs). RESULTS: Seven studies consisting of 1,162,971 participants with schizophrenia were included in this meta-analysis. Data regarding mortality risk of breast, colon, lung and prostate cancer among schizophrenia patients were subjected to quantitative analysis. Pooled results showed significant increases in mortality risk of breast cancer (RR = 1.97, 95%CI 1.38-2.83), lung cancer (RR = 1.93, 95%CI 1.46-2.54) and colon cancer (RR = 1.69, 95%CI 1.60-1.80) in patients with schizophrenia compared with those in the general population or control group. The mortality risk of prostate cancer increased in male patients, although no significant difference was detected (RR = 1.58, 95% CI 0.79-3.15). Increased risks of mortality from lung and colon cancer were observed in female patients (RR = 2.49, 95%CI 2.40-2.59 and RR = 2.42, 95%CI 1.39-4.22, respectively) and elevated risks of mortality from lung and colon cancer in male patients (RR = 2.40, 95%CI 2.30-2.50 and RR = 1.90, 95%CI 1.71-2.11, respectively) were detected. CONCLUSIONS: Individuals with schizophrenia have a significantly high risk of mortality from breast, colon, and lung cancer.

Functional Characterization of a Drought-Responsive Invertase Inhibitor from Maize (Zea mays L.).

Invertases (INVs) play essential roles in plant growth in response to environmental cues. Previous work showed that plant invertases can be post-translationally regulated by small protein inhibitors (INVINHs). Here, this study characterizes a proteinaceous inhibitor of INVs in maize (Zm-INVINH4). A functional analysis of the recombinant Zm-INVINH4 protein revealed that it inhibited both cell wall and vacuolar invertase activities from maize leaves. A Zm-INVINH4::green fluorescent protein fusion experiment indicated that this protein localized in the apoplast. Transcript analysis showed that Zm-INVINH4 is specifically expressed in maize sink tissues, such as the base part of the leaves and young kernels. Moreover, drought stress perturbation significantly induced Zm-INVINH4 expression, which was accompanied with a decrease of cell wall invertase (CWI) activities and an increase of sucrose accumulation in both base parts of the leaves 2 to 7 days after pollinated kernels. In summary, the results support the hypothesis that INV-related sink growth in response to drought treatment is (partially) caused by a silencing of INV activity via drought-induced induction of Zm-INVINH4 protein.

Association of BSG genetic polymorphisms with atherosclerotic cerebral infarction in the Han Chinese population.

The Basigin (BSG, also known as CD147/extracellular matrix metalloproteinase inducer) belongs to the immunoglobulin superfamily (IgSF). It is a cellular receptor for cyclophilin A (CypA), and is originally known as tumor cell collagenase stimulatory factor (TCSF), which could abundantly expressed on the surface of tumor cells, haematopoietic, monocytes, epithelial endothelial cells and smooth muscle cells. Accumulating evidence showed that BSG played an important role in stimulating the secretion of matrix metalloproteinases (MMPs), which has been reported to be involved in the development of atherosclerosis. Since atherosclerosis is an important risk factor for atherosclerotic cerebral infarction (ACI), we speculate that BSG genetic polymorphisms may influence formation of atherosclerosis and then development of ACI. This study aimed to detect the potential association of the single nucleotide polymorphisms (SNP, -631 G > T, -318 G > C, 10141 G > A and 10826 G > A) of BSG gene in Hunan Han Chinese population with ACI. We genotyped 199 ACI patients and 188 matched healthy controls for the four BSG SNP by method of matrix-assisted laser desorption/ionization-time-offlight mass spectrometry (MALDI-TOF MS). Our results suggested that all the polymorphisms were observed in the subjects from Changsha area of Hunan Province. However, no significant difference was observed between the distribution of these SNP in cases and controls. Therefore, we speculate that BSG genetic polymorphisms might not be an important factor in the development of ACI in our Chinese Han population.

Adjuvant trastuzumab for triple-positive breast cancer with chronic renal failure: A case report and review of literature.

RATIONALE: Although the occurrence of combined renal insufficiency among patients with breast cancer is even rarer, it poses a significant challenge in the treatment of these patients. Treating such patients often requires both targeted and endocrine therapies. However, oncologists lack evidence-based guidelines for managing renal function in patients with renal insufficiency. PATIENTS CONCERN: A 56-year-old menopausal female with a history of renal failure was diagnosed with triple-positive breast cancer and administered endocrine therapy and targeted therapy associated with hemodialysis after surgery. OUTCOMES: Under the premise of regular dialysis, the patient successfully completed endocrine therapy and targeted therapy for 1 year. DISCUSSION: Patients with advanced triple-positive breast cancer, including those undergoing hemodialysis, require a combination of anti-human epidermal growth factor receptor-2 and endocrine therapies, The side effects of these 2 treatment methods are worth considering in patients with renal insufficiency. CONCLUSION: We report a case of triple-positive breast cancer in a patient undergoing hemodialysis. There was no difference in the treatment approach between patients with and without normal renal function.

Effect of intravenous thrombolysis on core growth rate in patients with acute cerebral infarction.

Objective: This study aimed to investigate the effects of recombinant tissue plasminogen activator intravenous thrombolysis (IVT) on the core growth rate of acute ischemic stroke. Methods: Stroke patients with large vessel occlusion and non-recanalization from IVT treatment were retrospectively included in this study and divided into two groups: IVT and non-IVT. The core growth rate was estimated by the acute core volume on perfusion CT divided by the last known well time from stroke to CT perfusion. The primary endpoint was the core growth rate, the tissue outcome was 24 h-ASPECTS, and the clinical outcome was a 3-month modified Rankin score. Results: A total of 94 patients were included with 53 in the IVT group and 41 in the non-IVT group. There was no significant difference in age, gender, hypertension, diabetes, atrial fibrillation, acute NIHSS, and last known well time from stroke to CT perfusion acquisition between the two groups. The core growth rate in the IVT group was lower than that in the non-IVT group, which was statistically significant after multivariate adjustment (coefficient: -5.20, 95% CI= [-9.85, -0.56], p = 0.028). There was a significant interaction between the IVT and the collateral index in predicting the core growth rate. The analysis was then stratified according to the collateral index, and the results suggested that IVT reduced the core growth rate more significantly after the worsening of collateral circulation (coefficient: 15.38, 95% CI= [-26.25, -4.40], p = 0.007). The 3-month modified Rankin score and 24 h-ASPECTS were not statistically significant between the two groups. Conclusion: Intravenous thrombolysis reduces the core growth rate in patients with AIS, especially those with poor collateral status.

Prognostic value of platelet-to-lymphocyte ratio in neoadjuvant chemotherapy for solid tumors: A PRISMA-compliant meta-analysis.

INTRODUCTION: Previous research indicates that the platelet-to-lymphocyte ratio (PLR) may be an indicator of poor prognosis in many tumor types. However, the PLR is rarely described in patients undergoing neoadjuvant chemotherapy (NAC) for solid tumors. Thus, we performed a meta-analysis to investigate the prognostic value of this ratio for patients with solid tumors treated by NAC. METHODS: A comprehensive search of the literature was conducted using the PubMed, EMBASE, Cochrane Library, and Web of Science databases, followed by a manual search of references from the retrieved articles. Pooled hazard ratios (HRs) with 95% confidence interval (CIs) were used to evaluate the association between PLR and 3 outcomes, namely, overall survival, disease-free survival, and pathological complete response rate after NAC. RESULTS: Eighteen studies published no earlier than 2014 were included in our study. A lower PLR was associated with better overall survival (HR = 1.46, 95% CI, 1.11-1.92) and favorable disease-free survival (HR = 1.81, 95% CI, 1.27-2.59). A PLR that was higher than a certain cutoff was associated with a lower pathological complete response rate in patients with cancer who received NAC (Odds ratio = 1.93, 95% CI, 1.40-2.87). CONCLUSION: Elevated PLR is associated with poor prognosis in various solid tumors. PLR may be a useful biomarker in delineating those patients with poorer prognoses who may benefit from neoadjuvant therapies.

A γ-glutamylcysteine ligase AcGCL alleviates cadmium-inhibited fructooligosaccharides metabolism by modulating glutathione level in Allium cepa L.

Fructooligosaccharides (FOS) are important carbohydrates in plants. Cadmium (Cd) toxicity limits growth and development in several plant species. Whether FOS metabolism is affected by Cd and the molecular mechanisms of tolerance of the effects of Cd toxicity in plants remain enigmatic. In the present study, FOS metabolism was analyzed under Cd stress in onion (Allium cepa L.). Results showed that Cd stress can inhibit FOS accumulation in onion, followed by the upregulation of a putative onion γ-glutamylcysteine ligase gene AcGCL. Heterologous expression of the AcGCL protein in Escherichia coli revealed that this recombinant enzyme has GCL activity. Furthermore, overexpressing AcGCL significantly increased glutathione (GSH) accumulation in young onion roots under Cd treatment, accompanied by increased phytochelatin (PC) amount, and increased transcript expression of GSH synthetase (GS), and phytochelatin synthase (PCS) genes. Notably, compared with control, overexpressing AcGCL ameliorated Cd phytotoxicity on onion FOS metabolism, which correlated with increased FOS synthesis. Taken together, these results suggest that the function of AcGCL as a γ-glutamylcysteine ligase can alleviate Cd inhibited FOS metabolism by modulating GSH levels in onion.

The prognostic and clinicopathological significance of RBM3 in the survival of patients with tumor: A Prisma-compliant meta-analysis.

BACKGROUND: RNA-binding motif protein 3 (RBM3) plays an important role in carcinogenesis and tumor progression. However, the prognostic role of RBM3 in human carcinomas remains controversial. Therefore, we took a meta-analysis to research the association between the overall survival of patients with cancer and the expression of RBM3. METHODS: Systematic literature research identified 17 potentially eligible studies comprising 4976 patients in ten different cancer types. Two researchers independently screened the content and quality of studies and extracted data. Correlations of RBM3 expression and survival were analyzed and the hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated. RESULTS: In the pooled analysis, overexpression of RBM3 was related to improved overall survival (OS), recurrence-free survival (RFS), and disease-free survival (DFS) in patients with cancer having a pooled HR of 0.61 (HR = 0.61; 95% CI: 0.47-0.69), 0.57 (HR = 0.60; 95% CI: 0.50-0.71) and 0.54 (HR 0.54; 95% CI: 0.38-0.78). Besides, subgroup analysis proved that overexpression of RBM3 was related to improved OS in colorectal cancer (HR = 0.61, 95% CI: 0.43-0.86), melanoma (HR = 0.32, 95% CI: 0.20-0.52), and gastric cancer (HR = 0.51, 95% CI: 0.35-0.73). However, subgroup analysis according to tumor type revealed that overexpression of RBM3 was not related to better OS in breast carcinoma (HR = 0.52, 95% CI: 0.17-0.61). CONCLUSIONS: Our results indicated that RBM3 overexpression was significantly predictive of better prognosis in various human cancers. For certain tumors, overexpression RBM3 might be a marker of improved survival in humans with cancer, except for breast cancer.

Prognostic Role of the Activated p-AKT Molecule in Various Hematologic Malignancies and Solid Tumors: A Meta-Analysis.

Cancer is one of the main causes of human death worldwide. Recently, many studies have firmly established the causal relationship between oxidative stress and cancer initiation and progression. As a key protein in PI3K/Akt signaling pathway, p-AKT (phosphorylated Akt) participates in the process of oxidative stress and plays a prognostic role in various hematologic tumors and solid tumors. We conducted a comprehensive search of the PubMed, Embase and Cochrane libraries to identify studies published in the past decade involving cancer patients expressing p-AKT that reported overall survival (OS) during follow-up. In this study, 6,128 patients in total were evaluated from 29 enrolled articles, and we concluded that overexpression of p-AKT was closely related to worse OS in cancer patients with a hazard ratio (HR) of 2.33 (95% CI: 1.67-4.00). Furthermore, we conducted a subgroup analysis, and the results indicated that overexpression of p-AKT was associated with worse OS in hematological tumor (HR: 1.64, 95% CI: 1.41-1.92), and solid tumor (HR: 2.44, 95% CI: 1.61-5.26). High expression of p-AKT is related to poor prognosis of various hematologic tumors and solid tumors.

Apoplastic maize fructan exohydrolase Zm-6-FEH displays substrate specificity for levan and is induced by exposure to levan-producing bacteria.

Fructan exohydrolases (FEHs) are structurally related to cell wall invertases. While the latter are ubiquitous in higher plants, the role of FEHs in non-fructan species has remained enigmatic. To explore possible roles of FEHs in maize, a full length putative Zm-6-FEH-encoding cDNA was cloned displaying high sequence similarity with cell wall invertases. For functional characterization, Zm-6-FEH protein was expressed in Picha pastoris and in Nicotiana benthamiana leaves. Enzyme activity of recombinant Zm-6-FEH protein showed a strong preference for levan as substrate. Expression profiling in maize seedlings revealed higher transcript amounts in the more mature leaf parts as compared to the growth zone at the base of the leaf, in good correlation with FEH enzyme activities. Subcellular localization analysis indicated Zm-6-FEH location in the apoplast. Noteworthy, incubation of leaf discs with levan and co-incubation with high levan-producing bacteria selectively up-regulated transcript levels of Zm-6-FEH, accompanied by an increase of 6-FEH enzyme activity. In summary, the results indicate that Zm-6-FEH, a novel fructan exohydrolase of a non-fructan species, may have a role in plant defense against levan-producing bacteria.

Efficacy and safety of liposome-paclitaxel/liposome-paclitaxel combined with S-1 in 17 advanced gastric cancer patients with poor performance status.

BACKGROUND: To evaluate the efficacy and safety of liposome-paclitaxel (L-PTX)/L-PTX plus S-1 in advanced gastric cancer patients with poor performance status (PS). METHODS: We performed this retrospective study on 17 advanced gastric cancer patients with poor PS [rated as ≥2 based on the Eastern Cooperative Oncology Group (ECOG) scale] who underwent the following chemotherapy regimen: (I) L-PTX single-agent: L-PTX 60-80 mg/m2 given on days 1 and 8, in a 21-day cycle; (II) timed sequential (TS) regimen: L-PTX 60-80 mg/m2 given on days 1 and 8. S-1, 40-60 mg/m2 twice a day on days 1-14, in a 21-day cycle. Initially, some patients could not tolerate the 2-drug combination chemotherapy regimen, only L-PTX single-agent was given. After the patient's physical condition was improved, plus S-1 was also given. RESULTS: A total of 17 patients were studied. No complete response (CR) or partial response (PR) were observed in six patients, accounting for 35.29% (6/17). Stable disease (SD) was observed in five patients, accounting for 29.41% (5/17), and progressive disease (PD) in 6, accounting for 35.29% (6/17). The objective response and disease control rates were 35.29% (6/17) and 64.71% (11/17), respectively. The median progression-free survival (PFS) and median overall survival (OS) were 6.50 months [95% confidence interval (CI): 4.81-8.20] and 13.00 months (95% CI: 0.00-33.65), respectively. The most common hematological toxicities were neutropenia and anemia. CONCLUSIONS: L-PTX/L-PTX plus S-1 in the treatment of advanced gastric cancer patients with poor PS can prolong the patients' PFS and OS, and the toxicity is tolerable.

The Expression of microRNA-223 and FAM5C in Cerebral Infarction Patients with Diabetes Mellitus.

The aim of the study was to investigate the expression of miR-223 and FAM5C in the peripheral blood mononuclear cells (PBMCs) of cerebral infarction patients with or without diabetes. Sixteen cases with diabetes mellitus (DM), 14 cases with cerebral infarction (CI), 12 cases with cerebral infarction and diabetes mellitus (CIDM), and 18 healthy subjects were included in this study. Real-time PCR was used to quantify mRNA expression. Western blot was used to detect FAM5C protein level. Recombinant plasmids expressing miR-223-3p and 3' UTR of FAM5C were constructed. Dual-luciferase reporter system was used to analyze the binding of miR-223-3p to FAM5C 3' UTR. FAM5C mRNA and protein level were significantly higher in the PBMCs of CIDM patients compared with healthy controls (P < 0.05). miR-223-3p expression in PBMCs was significantly lower in DM patients than in healthy controls (P < 0.05). The expression of miR-223-3p was negatively correlated with FAM5C mRNA in all patients and healthy controls. Co-transfection of miR-223-3p plasmid with FAM5C 3'UTR dual-luciferase plasmid significantly inhibited the luciferase activity (P < 0.01). FAM5C, but not miR-223, is a risk factor for CI in type 2 DM patients.

Detection of platelet microRNA expression in patients with diabetes mellitus with or without ischemic stroke.

AIMS: The objective of this study was to investigate the role of plasma and platelet microRNAs in the occurrence of ischemic stroke in patients with diabetes mellitus. METHODS: miR-223, miR-146a, miR-495, and miR-107 expression in the plasma and platelets, blood glucose concentration, and platelet activation rate were measured in patients with diabetes mellitus and ischemic stroke, diabetes mellitus only, ischemic stroke only, and healthy controls. Platelet activity was measured by flow cytometric measurement of P-selectin expression, while miRNA was measured by real-time PCR. RESULTS: The expressions of platelet and plasma miR-223 and miR-146a were significantly downregulated in patients with ischemic stroke and diabetes mellitus or diabetes mellitus only, but not in patients with ischemic stroke only compared to healthy controls. The expressions of platelet and plasma miR-495 and miR-107 showed no significant differences among these four groups. The expression of platelet miR-223 and miR-146a significantly correlated with plasma miR-223 and miR-146a levels, blood glucose concentration, and platelet activation rate. CONCLUSIONS: Hyperglycemia may downregulate the expressions of miR-223 and miR-146a, leading to subsequent platelet activation in patients with diabetes mellitus. Low platelet and plasma miR-223 and miR-146a expression is a risk factor for ischemic stroke in Chinese diabetes mellitus patients.