Overall survival and short-term efficacy analysis of cervical squamous cell carcinoma with skeletal muscle and 18F-FDG PET/CT parameters.

2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) can provide tumor biological metabolism and skeletal muscle composition information. The aim of this study was to evaluate overall survival (OS) and short-term efficacy of cervical squamous cell carcinoma combining tumor biological metabolism and skeletal muscle composition parameters. Eighty two patients with cervical squamous cell carcinoma were included in the study, who received 18F-FDG PET/CT scans before treatment. Clinical characteristics, tumor biological metabolism parameters [standardized uptake value, metabolic tumor volume (MTV), total lesion glycolysis, heterogeneity of tumors, etc.] and body composition parameters were recorded. The survival analysis of cervical squamous cell carcinoma patients was performed by univariate and multivariate analysis. A combined model included clinical indicators, tumor metabolism parameters and sarcopenia was constructed to evaluate OS of patients. According to the Response Evaluation Criteria in Solid Tumours version 1.1, the relationship between sarcopenia with tumor metabolism parameters and short-term efficacy was investigated in subgroup. The results indicate that sarcopenia and high value of the sum of MTV of lesions and metastases (MTVtotal) were poor prognostic factors in patients with cervical squamous cell carcinoma. The combination of sarcopenia, MTVtotal and clinical factors provided an improved prediction of OS especially in the long term after treatment. Nutritional status of the patients and tumor metabolism may not affect the short-term efficacy of chemoradiotherapy in cervical squamous cell carcinoma patients.

The Role of High Mobility Group Box B-1 in the Prognosis of Colorectal Cancer Based on the Changes in the Intestinal Mucosal Barrier.

Background: To investigate the expression of high mobility group box B-1 (HMGB-1) in patients with colorectal cancer (CRC) and its association with clinicopathological features and prognosis in colorectal carcinoma by combining bioinformatics and clinical data analysis, and to clarify the role of HMGB-1. To examine whether HMGB-1 expression is related to the damage of the intestinal mucosal barrier, and then explore the potential HMGB-1-dependent mechanisms affecting the progression of CRC. Methods: CRC datasets of GSE12945, GSE17536, and GSE17537 from the public gene chip database were screened and downloaded. Clinical information and CRC tissue samples from patients with stage I-III CRC from the hospital were collected. Serum samples of patients were applied by enzyme-linked immunosorbent assay on HMGB-1, and were divided into high and low HMGB-1 expression, which was examined by 16S rDNA sequencing. Immunohistochemistry was performed to examine the relationship between the expression of HMGB-1 and tight junction protein, occludin, tumor necrosis factor-α, and interferon-γ. Results: Based on the Cutoff value of 10.24 ng/mL, the CRC patients were divided into high and low expression groups. In the HMGB-1H patient group, the TNM staging, overall survival, disease-free survival, recurrence, and metastasis were inferior to the HMGB-1L group. The results of 16S rDNA sequencing demonstrated that the Providencia genus was found to be enriched in the HMGB-1L group. Immunohistochemical results showed that HMGB-1 expression was negatively correlated with the expression of ZO-1 and occludin (R = 0.035, R = 0.003, P < .05), but was positively correlated with the expression of TNF-α and IFN-γ (R = 0.016, R = 0.001, P < .05). Conclusion: The survival of CRC patients with positive HMGB-1 expression was significantly shortened, which may be related to the decrease of Rovitensis content, the decreased expression of ZO-1 and occludin, and the increased levels of TNF-α and IFN-γ, which in turn damage the intestinal mucosal barrier, leading to the development of CRC.

Advantages of growth and competitive ability of the invasive plant Solanum rostratum over two co-occurring natives and the effects of nitrogen levels and forms.

Introduction: Atmospheric nitrogen (N) deposition has often been considered as a driver of exotic plant invasions. However, most related studies focused on the effects of soil N levels, and few on those of N forms, and few related studies were conducted in the fields. Methods: In this study, we grew Solanum rostratum, a notorious invader in arid/semi-arid and barren habitats, and two coexisting native plants Leymus chinensis and Agropyron cristatum in mono- and mixed cultures in the fields in Baicheng, northeast China, and investigated the effects of N levels and forms on the invasiveness of S. rostratum. Results: Compared with the two native plants, S. rostratum had higher aboveground and total biomass in both mono- and mixed monocultures under all N treatments, and higher competitive ability under almost all N treatments. N addition enhanced the growth and competitive advantage of the invader under most conditions, and facilitated invasion success of S. rostratum. The growth and competitive ability of the invader were higher under low nitrate relative to low ammonium treatment. The advantages of the invader were associated with its higher total leaf area and lower root to shoot ratio compared with the two native plants. The invader also had a higher light-saturated photosynthetic rate than the two native plants in mixed culture (not significant under high nitrate condition), but not in monoculture. Discussion: Our results indicated that N (especially nitrate) deposition may also promote invasion of exotic plants in arid/semi-arid and barren habitats, and the effects of N forms and interspecific competition need to be taken into consideration when studying the effects of N deposition on invasion of exotic plants.

A Research Study to Measure the Efficacy of Terminating Cervical Cancer via Customized Optimum Pathway.

Background: To develop a precise prognostic model of overall survival in patients with terminating cervical cancer based on surveillance, epidemiology, and end results (SEER) program. Methods: The patients were retrieved from SEER data who are diagnosed with terminating cervical cancer from 2004 to 2016. The data were performed using univariate and multivariate analyses and constructed nomograms for predicting survival. Use C-index to validate the model accuracy. Results: Totally 15839 patients diagnosed with cervical cancer were independently allocated into the training set (n = 11088) and validation set (n = 4751). The multivariate analysis results indicated that age, race, stage_T, stage_M, and stage_N were confirmed as independent risk predictors, and those factors are applied to construct this clinical model. The C-index of overall survival in the training set was 0.6816 (95% confidence intervene (CI), 0.694-0.763) and that in the validation set was 0.6931(95% CI, 0.613-0.779). All calibration curves of various factors were consistent with predicted and actual survival. Conclusion: The nomogram provides a novel method for predicting the survival of patients with terminating cervical cancer, assisting in accurate therapeutic methods for patients with primary terminating cervical cancer.

ITGA7, CD133, ALDH1 are inter-correlated, and linked with poor differentiation, lymph node metastasis as well as worse survival in surgical cervical cancer.

AIM: Integrin alpha 7 (ITGA7) regulates cancer stemness and metastasis in several malignancies, while its role in cervical cancer is obscure. Therefore, the current study aimed to investigate the correlation among ITGA7, cluster of differentiation 133 (CD133), and aldehyde dehydrogenase isoform 1 (ALDH1), as well as their relation to tumor features and survival in cervical cancer patients. METHODS: A total of 133 surgical cervical cancer patients were enrolled. Tumor ITGA7, CD133, and ALDH1 expressions were determined by immunohistochemistry (IHC). Furthermore, the clinicopathological features, disease-free survival (DFS), and overall survival (OS) were collected. RESULTS: ITGA7 expression positively related to CD133 expression (p = 0.040) and ALDH1 expression (p < 0.001). Besides, ITGA7 (p = 0.001), CD133 (p = 0.016), and ALDH1 (p = 0.009) high expressions linked with poor tumor differentiation; meanwhile, ITGA7 (p = 0.010) and ALDH1 (p = 0.004) high expressions correlated with more prevalence of lymph node metastasis. However, ITGA7, CD133, or ALDH1 expression was not associated with other clinicopathological features. Inspiringly, it was worth noting that ITGA7 (p = 0.009), CD133 (p = 0.041), and ALDH1 (p = 0.035) high expressions predicted unfavorable DFS; meanwhile, both ITGA7 (p = 0.021) and ALDH1 (p = 0.023) high expressions but not CD133 expression (p = 0.169) forecasted exasperated OS. CONCLUSION: ITGA7, CD133, ALDH1 are inter-correlated, and linked with poor differentiation, lymph node metastasis as well as worse survival in surgical cervical cancer.

miR-186-3p attenuates the tumorigenesis of cervical cancer via targeting insulin-like growth factor 1 to suppress PI3K-Akt signaling pathway.

miR-186-3p acts as a tumor suppressor in various cancers. This study aimed to explore the expression levels of miR-186-3p and its role in cervical cancer. We analyzed the effects of miR-186-3p and insulin-like growth factor 1 (IGF1) on the proliferation, invasion, and apoptosis of cervical cancer cells in vitro by regulating the PI3K/Akt signaling pathway. In cervical cancer tissues and cells, miR-186-3p was downregulated, and IGF1 was upregulated. In addition, miR-186-3p inhibited cell proliferation and invasion and enhanced apoptosis of cervical cancer cells. Moreover, our results showed that miR-186-3p inversely regulated the mRNA expression of IGF1 through direct contact. Knockdown of IGF1 reversed the results of miR-186-3p inhibitor in cervical cancer cells. In addition, the PI3K/Akt signaling pathway was activated by the miR-186-3p inhibitor, although partially arrested by IGF1 knockdown. The PI3K/Akt signaling pathway inhibitor suppressed miR-186-3p inhibitor-stimulated cell proliferation in cervical cancer. In conclusion, miR-186-3p inhibits tumorigenesis of cervical cancer by repressing IGF1, which inactivates the PI3K/Akt signaling pathway, implicating miR-186-3p as a potential new target for the treatment of cervical cancer.

MiR-186-3p attenuates tumorigenesis of cervical cancer by targeting IGF1.

BACKGROUND: Mounting evidence in the cancer literature suggests that microRNAs (miRNAs) influence the progression of human cancer cells by targeting protein-coding genes. How insulin-like growth factor 1(IGF1) and miR-186-3p contribute to the development of cervical cancer (CC) remains unclear. This study examined the regulatory roles of miR-186-3p and IGF1 in CC development. METHODS: Gene expression levels were determined by qRT-PCR. Proliferation, migration, and apoptosis of CC and normal cells were determined by MTT, Transwell, and caspase-3 activity assays, respectively. Dual-luciferase reporter activity and RNA pull-down assays were performed to identify the target gene of miR-186-3p. RESULTS: IGF1 was the target of miR-186-3p. The expression of miR-186-3p inhibited cell proliferation and migration abilities of CC cell lines, but induced the apoptosis rate of CC cells. IGF1 could restore the inhibitory effects of miR-186-3p on the proliferation, migration, and apoptosis abilities of CC cells. Experimental results revealed that miR-186-3p could inhibit IGF1 expression, thereby reducing the viability of CC cells. CONCLUSIONS: The data suggest that targeting of IGF1 by miR-186-3p could be crucial in regulating the progression of CC.

MicroRNA-186-3p attenuates tumorigenesis of cervical cancer by targeting MCM2.

The present study examined the effect of microRNA (miRNA/miR)-186-3p and its target gene, minichromosome maintenance complex component 2 (MCM2), on cervical cancer. Cervical cancer tissues and corresponding normal tissues were collected from 48 patients and bioinformatics analysis was performed to identify the differentially expressed genes in cervical cancer. TargetScan and TarBase were used to identify miRNAs, and reverse transcription-quantitative PCR was conducted to detect and evaluate mRNA expression levels. Additionally, MTT and 5-bromo-2-deoxyuridine assays were performed to examine cell proliferation. Cell adhesion, cell cycle distribution and apoptosis were assessed using cell adhesion, flow cytometry and caspase-3/7 activity assays, respectively. The results revealed that miR-186-3p expression was downregulated in cervical cancer tissues and cells, and it negatively regulated MCM2 expression by directly targeting its 3' untranslated region in cervical cancer. Furthermore, MCM2 facilitated cell proliferation and inhibited cell apoptosis, which were reversed by upregulation of miR-186-3p expression. Collectively, the present study suggested that MCM2 and its negative regulator, miR-186-3p, regulate cervical cancer progression.

Glutamate receptor, ionotropic, N-methyl D-aspartate-associated protein 1, a potential target of miR-296, facilitates proliferation and migration of rectal cancer cells.

The purpose of our article was to probe the influence of GRINA on rectal cancer and how GRINA is regulated in rectal cancer. Based on the public data, we found that GRINA was highly expressed in rectal cancer tissues and related to worse prognosis in rectal cancer patients. MiR-296 was predicted as an upstream regulatory miRNA of GRINA, which was further verified by dual-luciferase reporter assay. Moreover, we revealed that up-regulation/down-regulation of GRINA facilitated/suppressed SW1463/SW837 cell proliferation, migration, and invasion. Rescue assays indicated that the facilitating impact of GRINA on SW1463 cell proliferation and motility was abolished by miR-296 over-expression whilst the suppressing influence of GRINA on SW837 cell proliferation, migration, and invasion was reversed by miR-296 depletion. These consequences indicated that GRINA, which might be regulated by miR-296, acted stimulative important impact on rectal cancer cells, insinuating that GRINA might be a novel potential target for rectal cancer therapy.

Functional implications of miR-145/RCAN3 axis in the progression of cervical cancer.

Cervical cancer, as the second leading cause of death in women malignant tumor, is not optimistic about survival rate and late recurrence rate. RCAN3 has been reported to function in a variety of diseases, but its relationship with cervical cancer has not been reported. This study aimed to investigate whether RCAN3 contributes to the development of cervical cancer and its mechanism. RCAN3 expression was analyzed in 306 cervical cancer tissues and 13 normal healthy tissues from TCGA and GTEX databases. Kaplan-Meier analysis and Cox regression analysis were carried out to assess the potential function of RCAN3. Subsequently, the upstream regulatory miRNA of RCAN3 was predicted by bioinformatics and confirmed using dual luciferase reporter assay. CCK-8, colony formation assay, transwell assay were used for functional analysis of miR-145/RCAN3 axis in vitro. The results showed that RCAN3 was highly expressed in cervical cancer tissues, leading to poor prognosis, and could be used as a prognostic factor for cervical cancer. MiR-145 directly targeted RCAN3, which was lowly expressed in cervical cancer tissues and cell lines, and the higher the miR-145 expression, the longer the survival time of patients. Finally, from the functional experiments results we can see that miR-145 can inhibit the proliferation, migration and invasion of cervical cancer cells, but overexpression of RCAN3 can reverse miR-145-mediated inhibition. To sum up, miR-145/RCAN3 axis may serve as a potential therapeutic target to regulate the progression of cervical cancer.

Lesser leaf herbivore damage and structural defense and greater nutrient concentrations for invasive alien plants: Evidence from 47 pairs of invasive and non-invasive plants.

Empirical evidence of enemy release is still inconsistent for invasive alien plant species, although enemy release is the key assumption for both the enemy release hypothesis (ERH) and the evolution of increased competitive ability hypothesis (EICA). In addition, little effort has been made to test this assumption in terms of defense investment using a multi-species comparative approach. Using a phylogenetically controlled within-study meta-analytical approach, we compared leaf herbivore damage, structural defenses and nutrients between 47 pairs of invasive versus native and/or non-invasive alien plants in China. The invasive relative to the co-occurring native or non-invasive (native and non-invasive alien) plants incurred lesser leaf herbivore damage, had lesser leaf concentrations of cellulose, hemicellulose, lignin and carbon, lesser leaf density and carbon or lignin to nitrogen ratio but greater nutrients, which may facilitate success of the invasive plants. The lesser structural investment did not result in lesser leaf construction costs for the invaders, which may be associated with their greater leaf nitrogen concentration. However, the invasive plants were not significantly different from the non-invasive alien plants in any trait. Our results provide strong evidence for ERH, also are consistent with EICA, and indicate that enemy release may be an important factor in alien plant invasions.

The association between serum growth differentiation factor-15 and 3-month depression after acute ischemic stroke.

OBJECTIVE: The aim of this study was to assess the association between serum growth differentiation factor-15(GDF-15) and 3-month depression after acute ischemic stroke. METHODS: In this single-center prospective study, patients with first-ever acute ischemic stroke between March 2017 and November 2018 were included. Neurological and neuropsychological evaluations were conducted during the 3-month follow-up. The predictive value of GDF-15 to predict the post-stroke depression (PSD) within 3 months, was compared with other known predictors. RESULTS: The median level of GDF-15 in 310 stroke patients was 1285(IQR, 846-1934) ng/l. During the 3-month follow-up, 76 patients were defined as depression (24.5%; 95% confidence interval [CI]: 17.9%-29.3%), and GDF-15 levels in those patients were nearly more than 1 time greater as compared with patients who were free of depression (P < 0.001). Using the ROC curves, GDF-15 serum level at 1660 ng/l predicted the PSD with the highest sensitivity and specificity [67.1% and 77.4%, respectively; AUC=0.78, 95%CI: 0.72-0.84; P < 0.001]. Interestingly, When GDF-15 was added to the model containing established significant risk factors, AUROC (standard error) was increased from 0.81(0.029) to 0.88(0.020). A significant difference in the AUC between the established risk factors alone and the addition of GDF-15 was observed (difference, 0.07[0.009]; P = 0.001). In a multivariate model using the elevated levels of GDF-15 (≥cut-off=1660 ng/l) vs. normal (

Antitumor activity of chimeric antigen receptor NK-92 cells targeting PSCA anainst cervical cancer / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To construct and verify the anti-tumor activity of chimeric antigen receptor (CAR) modified NK-92 cells (CAR-NK-92 cells) targeting prostate stem cell antigen (PSCA) in cervical cancer. Methods: Lentiviral vector expressing CAR targeting PSCA was constructed, and PSCA CAR-NK-92 cells were obtained by lentivirus transfection. The expression of PSCA in human cervical cancer cells was determined by Flow cytometry and Western blotting. The killing effect of PSCA CAR-NK-92 cells against cervical cancer cells was verified by co-incubation of effector and target cells in vitro, and the tumor inhibitory ability of PSCA CAR-NK-92 cells was verified with the nude mice xenograft model in vivo. Results: PSCA CAR-NK-92 cells were successfully constructed. PSCA was highly expressed in human cervical cancer Hela and MS751 cells (all P<0.01). In vitro co-incubation results showed that PSCA CAR-NK-92 cells could lyse PSCA+ cervical cancer transplanted tumor in a dose-dependent manner. In vivo anti-tumor data showed that PSCA CAR-NK-92 cells significantly inhibited the growth of cervical cancer cells compared with NK-92 cells transfected with vehicle vectors (P<0.01). In addition, PSCA CAR-NK-92 cells could effectively infiltrate tumor tissues and promote the secretion of anti-tumor cytokines TNF-α and IFN-γ (all P<0.01). Conclusion: The CAR-NK-92 targeting PSCA shows good anti-tumor effect on PSCA+ tumor cells both in vitro and in vivo, and has potential to be a therapeutic strategy for cervical cancer.

Higher photosynthesis, nutrient- and energy-use efficiencies contribute to invasiveness of exotic plants in a nutrient poor habitat in northeast China.

The roles of photosynthesis-related traits in invasiveness of introduced plant species are still not well elucidated, especially in nutrient-poor habitats. In addition, little effort has been made to determine the physiological causes and consequences of the difference in these traits between invasive and native plants. To address these problems, we compared the differences in 16 leaf functional traits related to light-saturated photosynthetic rate (Pmax ) between 22 invasive and native plants in a nutrient-poor habitat in northeast China. The invasive plants had significantly higher Pmax , photosynthetic nitrogen- (PNUE), phosphorus- (PPUE), potassium- (PKUE) and energy-use efficiencies (PEUE) than the co-occurring natives, while leaf nutrient concentrations, construction cost (CC) and specific leaf area were not significantly different between the invasive and native plants. The higher PNUE contributed to higher Pmax for the invasive plants, which in turn contributed to higher PPUE, PKUE and PEUE. CC changed independently with other traits such as Pmax , PNUE, PPUE, PKUE and PEUE, showing two trait dimensions, which may facilitate acclimation to multifarious niche dimensions. Our results indicate that the invasive plants have a superior resource-use strategy, i.e. higher photosynthesis under similar resource investments, contributing to invasion success in the barren habitat.

Essential tremor is associated with disruption of functional connectivity in the ventral intermediate Nucleus--Motor Cortex--Cerebellum circuit.

The clinical benefits of targeting the ventral intermediate nucleus (VIM) for the treatment of tremors in essential tremor (ET) patients suggest that the VIM is a key hub in the network of tremor generation and propagation and that the VIM can be considered as a seed region to study the tremor network. However, little is known about the central tremor network in ET patients. Twenty-six ET patients and 26 matched healthy controls (HCs) were included in this study. After considering structural and head-motion factors and establishing the accuracy of our seed region, a VIM seed-based functional connectivity (FC) analysis of resting-state functional magnetic resonance imaging (RS-fMRI) data was performed to characterize the VIM FC network in ET patients. We found that ET patients and HCs shared a similar VIM FC network that was generally consistent with the VIM anatomical connectivity network inferred from normal nonhuman primates and healthy humans. Compared with HCs, ET patients displayed VIM-related FC changes, primarily within the VIM-motor cortex (MC)-cerebellum (CBLM) circuit, which included decreased FC in the CBLM and increased FC in the MC. Importantly, tremor severity correlated with these FC changes. These findings provide the first evidence that the pathological tremors observed in ET patients might be based on a physiologically pre-existing VIM - MC - CBLM network and that disruption of FC in this physiological network is associated with ET. Further, these findings demonstrate a potential approach for elucidating the neural network mechanisms underlying this disease.

Multiple Resting-State Networks Are Associated With Tremors and Cognitive Features in Essential Tremor.

INTRODUCTION: The heterogeneous clinical features of essential tremor indicate that the dysfunctions of this syndrome are not confined to motor networks, but extend to nonmotor networks. Currently, these neural network dysfunctions in essential tremor remain unclear. In this study, independent component analysis of resting-state functional MRI was used to study these neural network mechanisms. METHODS: Thirty-five essential tremor patients and 35 matched healthy controls with clinical and neuropsychological tests were included, and eight resting-state networks were identified. After considering the structure and head-motion factors and testing the reliability of the selected resting-state networks, we assessed the functional connectivity changes within or between resting-state networks. Finally, image-behavior correlation analysis was performed. RESULTS: Compared to healthy controls, essential tremor patients displayed increased functional connectivity in the sensorimotor and salience networks and decreased functional connectivity in the cerebellum network. Additionally, increased functional network connectivity was observed between anterior and posterior default mode networks, and a decreased functional network connectivity was noted between the cerebellum network and the sensorimotor and posterior default mode networks. Importantly, the functional connectivity changes within and between these resting-state networks were correlated with the tremor severity and total cognitive scores of essential tremor patients. CONCLUSIONS: The findings of this study provide the first evidence that functional connectivity changes within and between multiple resting-state networks are associated with tremors and cognitive features of essential tremor, and this work demonstrates a potential approach for identifying the underlying neural network mechanisms of this syndrome.