Early outcomes, associated factors and predictive values of clinical outcomes of tandospirone in generalized anxiety disorder: a post-hoc analysis of a randomized, controlled, multicenter clinical trial.

OBJECTIVE: To examine the early outcomes, associated factors and predictive values of clinical outcomes of different tandospirone doses in patients with a generalized anxiety disorder (GAD). METHODS: This was a posthoc analysis of "a randomized, controlled multicenter clinical trial of the efficacy and safety of different doses of tandospirone on GAD". A total of 274 patients with GAD were included and randomized into the high-dose (tandospirone 60 mg/d) and low-dose (tandospirone 30 mg/d) groups for a 6-week treatment. The Hamilton Anxiety (HAMA), Clinical Global Impression-Severity (CGI-S), Short-Form-12 (SF-12) scales were used for assessment. The trial was registered at clinical trail.gov (NCT01614041). RESULTS: (1) In the first week of treatment, 35.8% of patients in the high-dose group fulfilled the early onset criteria, which was significantly higher than 19.0% found in the low-dose group (p = 0.002). In the second week of treatment, 22.6% of patients in the high-dose group achieved an early response, versus 12.4% in the low-dose group, indicating a significant difference (p = .026). (2) Factors associated with early onset at week 1 included baseline HAMA total score (OR = 0.916, 95%CI 0.882-0.952), age (OR = 0.974, 95%CI 0.950-0.998), drug dose (30 mg vs. 60 mg; OR = 0.298, 95%CI 0.156-0.568) and SF-12 physiological total score (OR = 1.030, 95%CI 1.010-1.050). (3) Early onset was significantly associated with response rate (OR = 18.34, 95%CI 12.10-27.81), remarkable response rate (OR = 27.56, 95%CI 11.65-65.17) and recovery rate (OR = 11.85, 95%CI 4.98-28.18). Group (high dose group vs. low dose group) (χ2 = 8.535, p = .003) and baseline HAMA total score (χ2 = 70.840, p < .001) were independent predictors of onset time. CONCLUSIONS: The early outcomes of high-dose tandospirone in the treatment of GAD are better than those of the low-dose group. Patients with younger age at onset, milder anxiety symptoms and better physiological functions administered high-dose tandospirone showed rapid onset, great early outcomes, high recovery rate and good prognosis. Drug onset time had a good predictive effect on treatment outcome.

A Design Method of Two-Dimensional Subwavelength Grating Filter Based on Deep Learning Series Feedback Neural Network.

Subwavelength grating structure has excellent filtering characteristics, and its traditional design method needs a lot of computational costs. This work proposed a design method of two-dimensional subwavelength grating filter based on a series feedback neural network, which can realize forward simulation and backward design. It was programed in Python to study the filtering characteristics of two-dimensional subwavelength grating in the range of 0.4-0.7 µm. The shape, height, period, duty cycle, and waveguide layer height of two-dimensional subwavelength grating were taken into consideration. The dataset, containing 46,080 groups of data, was generated through numerical simulation of rigorous coupled-wave analysis (RCWA). The optimal network was five layers, 128 × 512 × 512 × 128 × 61 nodes, and 64 batch size. The loss function of the series feedback neural network is as low as 0.024. Meanwhile, it solves the problem of non-convergence of the network reverse design due to the non-uniqueness of data. The series feedback neural network can give the geometrical structure parameters of two-dimensional subwavelength grating within 1.12 s, and the correlation between the design results and the theoretical spectrum is greater than 0.65, which belongs to a strong correlation. This study provides a new method for the design of two-dimensional subwavelength grating, which is quicker and more accurate compared with the traditional method.

Surgery in platinum-resistant recurrent epithelial ovarian carcinoma.

BACKGROUND: Ovarian cancer is one of the three most common malignant tumors of the female reproductive tract and ranks first in terms of mortality among gynecological tumors. Epithelial ovarian carcinoma (EOC) is the most common ovarian malignancy, accounting for 90% of all primary ovarian tumors. The clinical value of cytoreductive surgery in patients with platinum-resistant recurrent EOC remains largely unclear. AIM: To evaluate the feasibility of secondary cytoreductive surgery for treating platinum-resistant recurrent EOC. METHODS: This was a retrospective study of the clinical data of patients with platinum-resistant EOC admitted to the Cancer Hospital of the University of Chinese Academy of Sciences between September 2012 and June 2018. Patient baseline data were obtained from clinical records. Routine follow-up of disease progression was performed as follows. CA125 assessment and physical examination were performed every 3 wk during treatment, including gynecological examination. Imaging assessment was carried out every 12 wk by B-mode ultrasound, computed tomography, or magnetic resonance imaging. The primary outcome was progression-free survival (PFS). Secondary outcomes included overall survival (OS), chemotherapy-free interval (CFI), and complications. Follow-up ended on April 15, 2019. RESULTS: A total of 38 patients were included. R0 resection was achieved in 25 (65.8%) patients and R1/2 in 13 (34.2%). Twenty-five (65.8%) patients required organ resection. Nine (23.7%) patients had operative complications, 36 (94.7%) received chemotherapy, and five (13.2%) had targeted therapy. Median PFS and OS were 10 (95%CI: 8.27-11.73) months and 28 (95%CI: 12.75-43.25) months, respectively; median CFI was 9 (95%CI: 8.06-9.94) months. R0 resection and postoperative chemotherapy significantly prolonged PFS and OS (all P < 0.05), and R0 resection also significantly prolonged CFI (P < 0.05). Grade ≥ 3 complications were observed, including rectovaginal fistula (n = 1), intestinal and urinary fistulas (n = 1), and renal failure-associated death (n = 1). Except for the patient who died after surgery, all other patients with complications were successfully managed. Two patients developed intestinal obstruction and showed improvement after conservative treatment. CONCLUSION: Secondary cytoreductive surgery is feasible for treating platinum-resistant recurrent EOC. These findings provide important references for the selection of clinical therapeutic regimens.

Predicting the risk of suicide attempt in a depressed population: Development and assessment of an efficient predictive nomogram.

The purpose of this study was to develop and validate a user-friendly suicide attempt risk nomogram in depression, supporting timely interventions by clinicians. We collected clinical data of 273 depressed patients from January 2020 to January 2021. Suicide attempt was assessed conducting the Mini International Neuropsychiatric Interview. First, optimized features were filtrated through the least absolute shrinkage and selection operator regression analysis. Subsequently, we selected variables with nonzero coefficients and entered them into multiple logistic regression model and nomogram function to construct a visual predicting suicide attempt model. Additionally, the C-index, calibration plot and decision curve analysis, were applied to assess discrimination, calibration, and clinical practicability. Finally, the bootstrapping validation was applied to assess internal validation. Finally, eleven clinical features are screened out in the prediction nomogram. The model presented tiptop calibration and pleasant discrimination with a C-index of 0.853. A towering C-index value, up to 0.799, could also be attained in the interval validation analysis. In addition, decision curve analysis exhibited that our predictive model is clinically effective when the threshold is no less than 1%. These results demonstrate this predictive model was helpful for clinicians assessing the inpatient's suicide attempt recently and implementing individualized treatment strategies.

Shotgun metagenomics reveals both taxonomic and tryptophan pathway differences of gut microbiota in major depressive disorder patients.

BACKGROUND: The microbiota-gut-brain axis, especially the microbial tryptophan (Trp) biosynthesis and metabolism pathway (MiTBamp), may play a critical role in the pathogenesis of major depressive disorder (MDD). However, studies on the MiTBamp in MDD are lacking. The aim of the present study was to analyze the gut microbiota composition and the MiTBamp in MDD patients. METHODS: We performed shotgun metagenomic sequencing of stool samples from 26 MDD patients and 29 healthy controls (HCs). In addition to the microbiota community and the MiTBamp analyses, we also built a classification based on the Random Forests (RF) and Boruta algorithm to identify the gut microbiota as biomarkers for MDD. RESULTS: The Bacteroidetes abundance was strongly reduced whereas that of Actinobacteria was significantly increased in the MDD patients compared with the abundance in the HCs. Most noteworthy, the MDD patients had increased levels of Bifidobacterium, which is commonly used as a probiotic. Four Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologies (KOs) (K01817, K11358, K01626, K01667) abundances in the MiTBamp were significantly lower in the MDD group. Furthermore, we found a negative correlation between the K01626 abundance and the HAMD scores in the MDD group. Finally, RF classification at the genus level can achieve an area under the receiver operating characteristic curve of 0.890. CONCLUSIONS: The present findings enabled a better understanding of the changes in gut microbiota and the related Trp pathway in MDD. Alterations of the gut microbiota may have the potential as biomarkers for distinguishing MDD patients form HCs.

Shotgun metagenomics reveals both taxonomic and tryptophan pathway differences of gut microbiota in bipolar disorder with current major depressive episode patients.

BACKGROUND: The microbiome-gut-brain axis, especially the microbial tryptophan biosynthesis and metabolism pathway (MiTBamp), is closely connected to bipolar disorder with current major depressive episode (BPD). METHODS: We performed shotgun metagenomics sequencing (SMS) of faecal samples from 25 BPD patients and 28 healthy controls (HCs). Except for the microbiota taxa and MiTBamp analyses, we also built a classification model using the Random Forests (RF) and Boruta algorithm to find the microbial biomarkers for BPD. RESULTS: Compared to HCs, the phylum Bacteroidetes abundance was significantly reduced, whereas that of the Actinobacteria and Firmicutes were significantly increased in BPD patients. We also identified 38 species increased and 6 species decreased significantly in the BPD group. In the MiTBamp, we identified that two Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologies (KOs) (K00658 and K00837) were significantly lower in the BPD, and five KOs (K01696, K00382, K00626, K01667, and K03781) were significantly higher in the BPD group. We also identified significant genera and species which were closely related to these KOs. Finally, RF classification based on gut microbiota at the genus level can achieve an area under the receiver operating characteristic curve of 0.997. LIMITATIONS: The features of cross-sectional design, limited sample size, the heterogeneity of bipolar disorders, and a lack of serum/plasma tryptophan concentration measurements. CONCLUSIONS: The present findings enable a better understanding of changes in gastrointestinal microbiome and MiTBamp in BPD. Alterations of microbes may have potential as biomarkers for distinguishing the BPD patients form HCs.

Potential Repressive Impact of microRNA-20a on Renal Tubular Damage in Diabetic Kidney Disease by Targeting C-X-C Motif Chemokine Ligand 6.

BACKGROUND AND AIMS: C-X-C Motif Chemokine Ligand 6 (CXCL6) is an important chemokine. We attempt in this investigation to explore its role and possible mechanism in diabetic kidney disease (DKD). METHODS: By intergrating GEO data, CXCL6 expression in DKD patients and normal controls was exhibited. miRWalk website and luciferase reporter assay were used to predict and verify the upstream miRNA of CXCL6. CCK-8 assay and flow cytometry were performed to detect proliferation and apoptosis capacities. The levels of inflammatory key factors (TNF-α, IL-6 and IL-8) were measured using ELISA analysis. Expression of CXCL6, miR-20a, and JAK/STAT3 pathway-related markers were detected by qRT-PCR or western blot assays. RESULTS: CXCL6 was increased in DKD. miR-20a was identified as an upstream regulatory miRNA of CXCL6, and its expression was decreased in DKD and HG-treated HK-2 cells. miR-20a overexpression facilitated the proliferation of HG-treated HK-2 cells, whereas miR-20a depletion exhibited the opposite phenomenon. The levels of TNF-α, IL-6 and IL-8 were increased by HG treatment in HK-2 cells. CXCL6 antagonized the promoting impacts of miR-20a mimics on HG-exposed HK-2 cell proliferation. The suppressive effect of miR-20a overexpression on apoptosis and inflammatory response of HG-induced HK-2 cell was rescued by CXCL6 enhancement. The protein expression of p-JAK and p-STAT3 were reduced by miR-20a mimic while facilitated by CXCL6 overexpression in HG-stimulated HK-2 cells. CONCLUSION: These consequences hinted that miR-20a might exert a repressive impact on DKD, possibly through targeting CXCL6 and mediating JAK/STAT3 pathway, which offer new targets for DKD treatment.

DACH1, a novel target of miR-218, participates in the regulation of cell viability, apoptosis, inflammatory response, and epithelial-mesenchymal transition process in renal tubule cells treated by high-glucose.

Objective: This report was designed to assess the functional role of miR-218/dachshund family transcription factor 1 (DACH1) in diabetic kidney disease (DKD) and investigate its possible molecular mechanism.Materials and Methods: From the GEO database, we downloaded different datasets for analyzing the expression of miR-218 and DACH1 in DKD. TargetScan was adopted to predict the binding sites between miR-218 and DACH1, which was further verified by dual-luciferase reporter assays. The renal proximal tubule cells (HK-2) treated with high glucose (HG) were used as an in vitro model. QRT-PCR and western blot were used to determine the expression of DACH1 and other relative factors. Cell counting kit-8 and flow cytometer were applied to detect cell viability and apoptosis. The levels of inflammatory cytokines were determined by an ELISA assay.Results: A prominent raise of miR-218 was observed in DKD through bioinformatics analysis, which was further confirmed in the HG-induced model. DACH1 is a target of miR-218. miR-218 reduced cell viability and induced apoptosis by negatively regulating DACH1. Moreover, upregulating miR-218 in HG models increased the concentrations of pro-inflammatory cytokines TNF-α and IL-1ß, reduced the level of anti-inflammatory cytokine IL-10, and promoted the epithelial-mesenchymal transition (EMT) process, which is possibly achieved by targeting DACH1. While downregulating miR-218 showed the opposite results.Conclusion: These data demonstrated that, under an in vitro HG environment, miR-218 suppressed the HK-2 cells proliferation, promoted apoptosis, caused an inflammatory response, and facilitated the EMT process largely by targeting DACH1, providing an insight into the therapeutic intervention of DKD.

Study protocol for a parallel-group, double-blinded, randomized, controlled, noninferiority trial: the effect and safety of hybrid electroconvulsive therapy (Hybrid-ECT) compared with routine electroconvulsive therapy in patients with depression.

BACKGROUND: Electroconvulsive therapy (ECT) is the most rapid and effective treatment for patients with depression, ECT can achieve remarkable antidepressant effects in the initial 3-4 sessions, but significant side effects limit its use. However, recent low-charge electrotherapy (LCE) studies have demonstrated antidepressant or antipsychotic effects with significantly fewer side effects. The aim of this study is to propose a novel two-step charge set strategy for ECT treatment, referred to as Hybrid-ECT, to decrease side effects by using a low charge while preserving treatment efficacy. METHODS/DESIGN: A randomized, double-blinded, standard-controlled, parallel-group design will be carried out. We plan to enroll 112 inpatients diagnosed with depression (unipolar or bipolar) and randomly assign them to conventional ECT (control group) or to Hybrid-ECT (treatment group, 3 ECT sessions followed by LCE sessions (approximately 2.8 joules per session)). We will evaluate participants across a wide variety of domains including clinical symptoms, cognitive, psychological and functional metrics. We will also perform magnetic resonance imaging (MRI) and event-related potential (ERPs) assessments during treatment to explore brain function differences between ECT and LCE. DISCUSSION: This research proposes a simple but completely novel ECT strategy that aims to rapidly relieve depressive symptoms and minimize side effects. The mechanism of ECT and LCE will be further discussed. TRIAL REGISTRATION: Chinese Clinical Trial Registry, Number: ChiCTR1900022905 (Registration date: April 30, 2019).

Downregulation of LINC00515 in high-grade serous ovarian cancer and its relationship with platinum resistance.

Aim: To investigate the expression of long intergenic noncoding RNA 00515 (LINC00515) in high-grade serous ovarian cancer (HGSOC) and its potential correlation with platinum resistance. Patients & methods: Expression of LINC00515 in HGSOC (n = 115) and normal (n = 19) tissues was detected via quantitative real-time PCR (qRT-PCR). We further explored the statistical significance of the relationship between LINC00515 expression and platinum resistance in HGSOC. Results: LINC00515 was gradually downregulated in the order of normal > platinum-sensitive > platinum-resistant tissue (p < 0.05). Results demonstrated that LINC00515 downregulation was correlated with platinum resistance and relapse-free survival (RFS) of HGSOC (p < 0.05). Conclusion: LINC00515 downregulation is correlated with HGSOC development, platinum resistance and RFS, supporting its utility as a potential biomarker to predict platinum resistance and prognosis of RFS.

Similarly in depression, nuances of gut microbiota: Evidences from a shotgun metagenomics sequencing study on major depressive disorder versus bipolar disorder with current major depressive episode patients.

BACKGROUND: To probe the differences of gut microbiota among major depressive disorder (MDD), bipolar disorder with current major depressive episode (BPD) and health participants. METHODS: Thirty one MDD patients, thirty BPD patients, and thirty healthy controls (HCs) were recruited. All the faecal samples were analyzed by shotgun metagenomics sequencing. Except for routine analyses of alpha diversity, we specially designed a new indicator, the Gm coefficient, to evaluate the inequality of relative abundances of microbiota for each participant. RESULTS: The Gm coefficients are significant decreased in both MDD and BPD groups. The relative abundances of increased phyla Firmicutes and Actinobacteria and decreased Bacteroidetes were significantly in the MDD and BPD groups. At genus level, four of top five enriched genera (Bacteroides, Clostridium, Bifidobacterium, Oscillibacter and Streptococcus) were found increased significantly in the MDD and BPD groups compared with HCs. The genera Escherichia and Klebsiella showed significant changes in abundances only between the BPD and HC groups. At the species level, compared with BPD patients, MDD patients had a higher abundance of Prevotellaceae including Prevotella denticola F0289, Prevotella intermedia 17, Prevotella ruminicola, and Prevotella intermedia. Furthermore, the abundance of Fusobacteriaceae, Escherichia blattae DSM 4481 and Klebsiella oxytoca were significantly increased, whereas the Bifidobacterium longum subsp. infantis ATCC 15697 = JCM 1222 was significantly reduced in BPD group compared with MDD group. CONCLUSIONS: Our study suggested that gut microbiota may be involved in the pathogenesis of both MDD and BPD patients, and the nuances of bacteria may have the potentiality of being the biomarkers of MDD and BPD.

Associations of serotonin transporter gene promoter polymorphisms and monoamine oxidase A gene polymorphisms with oppositional defiant disorder in a Chinese Han population.

BACKGROUND: Oppositional defiant disorder (ODD) is a behavioral disorder that mainly refers to a recurrent pattern of disobedient, defiant, negativistic and hostile behaviors toward authority figures. Previous studies have showed associations of serotonin transporter (5-HTT) and monoamine oxidase A (MAOA) with behavioral and psychiatric disorders. The purposes of this study were to investigate the potential association of 5-HTT gene promoter polymorphism (5-HTTLPR) and MAOA gene polymorphism with susceptibility to ODD in a Han Chinese school population. METHODS: The 5-HTTLPR gene polymorphism and the MAOA gene polymorphism were genotyped in a case-control study of 257 Han Chinese children (123 ODD and 134 healthy controls). RESULTS: There was significant difference in the allele distribution of 5-HTTLPR (χ2 = 7.849, P = 0.005) between the ODD and control groups. Further, there were significant differences in genotype (χ2 = 5.168, P = 0.023) and allele distributions (χ2 = 10.336, P = 0.001) of the MAOA gene polymorphism that is variable-number tandem repeat (MAOA-uVNTR) between two groups. Moreover, there were significant differences in genotype (χ2 = 4.624, P = 0.032) and allele distributions (χ2 = 9.248, P = 0.002) of MAOA-uVNTR only in the male ODD and healthy groups. CONCLUSIONS: Our results suggest that 5-HTTLPR and MAOA-uVNTR gene variants may contribute to susceptibility to ODD. Further, MAOA-uVNTR gene polymorphism may play a role in susceptibility to ODD only in male children.

Natural antisense transcript TPM1-AS regulates the alternative splicing of tropomyosin I through an interaction with RNA-binding motif protein 4.

LncRNAs play a vital role in alternative splicing of target genes. However, the mechanisms underlying lncRNAs involvement in splicing are poorly understood. In the present study, we identified a previously uncharacterized lncRNA, which is denoted as TPM1-AS, is reverse-transcribed from the fourth intronic region of the tropomyosin I (TPM1). In situ hybridization and RNA immunoprecipitation assays demonstrated that TPM1-AS was located in the nucleus and interacted with RNA-binding motif protein 4 (RBM4) in human esophageal cancer cells. TPM1-AS overexpression or RBM4 knockdown decreased endogenous exon 2a expression of TPM1, resulting in specifically down-regulation of TPM1variant V2 and V7 in human esophageal cancer cells. Mechanismly, the interaction of TPM1-AS with RBM4 hindered binding of RBM4 to TPM1 pre-mRNA and inhibited RBM4 to promote endogenous exon 2a inclusion of TPM1. Importantly, overexpression of TPM1-AS inhibited migration and filopodium formation, whereas TPM1variant V2 and V7 promoted these behaviors of human esophageal cancer cells. Taken together, the results suggest that a natural antisense TPM1-AS regulates the alternative splicing of TPM1 through an interaction with RBM4 and involves in TPM1-mediated filopodium formation and migration of cancer cells.

Xiaoaiping combined with cisplatin can inhibit proliferation and invasion and induce cell cycle arrest and apoptosis in human ovarian cancer cell lines.

PURPOSE: The aim of the present study was utilizing Xiaoaiping as a single agent or combined with cisplatin to study its effect on the ovarian cancer cells (HO-8910 and HO-8910PM cells) in tumor cell proliferation, cell apoptosis, cell cycle distribution and cell invasion and migration. METHODS: Both HO-8910 and HO-8910PM cell lines were treated with Xiaoaiping injection, cisplatin or combination. Effects on the cell viability and apoptosis induction were estimated using the Cell counting Kit-8 assay and Annexin V-FITC/Propidium Iodide staining. The distribution of cells in different phases of the cell cycle was assayed using flow cytometry analysis. The effects of Xiaoaiping on the inhibition of cell invasion and migration were researched with Transwell cell migration. RESULTS: Both Xiaoaiping and cisplatin significantly decreased the HO-8910 cell survival versus control arm. Combination treatment showed a higher cytotoxicity to cells in vitro than Xiaoaiping and cisplatin alone. An increase in the G0/G1 phase fraction in HO-8910 cells treated with either Xiaoaiping or cisplatin alone was evident when compared to the fraction in control arm. Compared to the effects of treatment with either agent alone, combination treatment significantly increased the fraction of cells in G0/G1 phase. The HO-8910 cell lines treated with cisplatin demonstrated a significant increase of apoptotic cell rate compared to untreated cell lines. The rate of apoptosis in combined treatment group was significantly higher than that of the single agent treatment groups. A significant reduction in the number of invading cells was observed for Xiaoaiping-treated HO-8910 cells compared with the control group. However, cisplatin did not significantly induce the migration of cells versus untreated cells. Combination of Xiaoaiping and cisplatin significantly suppressed cell invasion and migration versus single-drug treatment in HO-8910 cells. The results of HO-8910PM cells were similar with HO-8910 cells in all tests. CONCLUSIONS: In summary, our results showed that Xiaoaiping as a single agent or combined with cisplatin could induce cell cycle arrest, cause apoptosis and necrosis in ovarian cancer cells, and inhibit cell invasion and migration. The present study also laid a foundation for further investigation involving molecular mechanism. Above all, it may provide a novel therapeutic regimen for ovarian cancer.

LncRNA-ANCR down-regulation suppresses invasion and migration of colorectal cancer cells by regulating EZH2 expression.

Our study aimed to explore the effects of long noncoding RNA (lncRNA)-ANCR on the invasion and migration of colorectal cancer (CRC) cells by regulating enhancer of zeste homolog 2 (EZH2) expression. CRC tissues and adjacent normal tissues were collected and CRC SW620 cells line and normal human intestinal epithelial cells (HIECs) were incubated. CRC SW620 cells line was transfected with ANCR-siRNA. The expressions of ANCR and EZH2 mRNA were measured by real-time quantitative polymerase chain reaction (RT-qPCR). EZH2 and trimethylation of H3K27 (H3K27me3) protein expressions were detected using Western blotting. The relationship between ANCR and EZH2 was determined through RNA pull-down and co-immunoprecipitation (co-IP) assays. Cell invasion and migration were determined by Trans-well and cell scratch assays. ANCR, EZH2 and H3K27me3 expressions were up-regulated in CRC tissues and SW620 cells (all P < 0.05). After transfected with ANCR-siRNA, SW620 cells showed decreased ANCR expression and EZH2 mRNA and protein expressions (all P < 0.05). According to the results of RNA pull-down and co-IP assays, ANCR could specifically bind to EZH2. The results of Trans-well and cell scratch tests showed that when ANCR expression was decreased, the invasion and migration abilities of SW620 cells significantly declined (both P < 0.05). In conclusion, these results suggest that lncRNA-ANCR could influence the invasion and migration of CRC cells by specifically binding to EZH2.

Venlafaxine ameliorates the depression-like behaviors and hippocampal S100B expression in a rat depression model.

BACKGROUND: Accumulating evidence has indicated that S100B may be involved in the pathophysiology of depression. No published study has examined the effect of the antidepressant drug venlafaxine on S100B in animal models of depression. This study investigated S100B expression in the hippocampus and assessed the effect of venlafaxine on S100B mRNA level and protein expression in rats exposed to chronic unpredictable mild stress (CUMS). METHODS: Forty Sprague-Dawley rats were randomly divided into four groups as control, 0, 5 and 10 mg venlafaxine groups. The venlafaxine groups were exposed to CUMS from day 2 to day 43. Venlafaxine 0, 5 and 10 mg/kg were then administered from day 23 to day 43. We performed behavioral assessments with weight change, open-field and sucrose preference, and analyzed S100B protein expression and mRNA level in the hippocampus. RESULTS: The CUMS led to a decrease in body weight, locomotor activity and sucrose consumption, but venlafaxine treatment (10 mg) reversed these CUMS-induced decreases Also, CUMS increased S100B protein expression and mRNA level in the hippocampus, but venlafaxine treatment (10 mg) significantly decreased S100B protein expression and mRNA level, which were significantly lower than the other treatment groups, without significant difference between the 10 mg venlafaxine and the control groups. CONCLUSIONS: Our findings showed that venlafaxine treatment (10 mg) may improve the depression-like behaviors and decrease over-expression of S100B protein and mRNA in the hippocampus in a rat model of depression.

Association of tryptophan hydroxylase-2 polymorphisms with oppositional defiant disorder in a Chinese Han population.

BACKGROUND: Oppositional defiant disorder (ODD) is a behavioral disorder of school-age population. It is well known that 5-HT dysfunction is correlated with impulsivity, which is one of the common characteristics of ODD. The enzyme tryptophan hydroxylase-2 (TPH-2) synthesizes 5-HT in serotonergic neurons of the midbrain raphe. The purposes of this study were to investigate the potential association of TPH-2 polymorphisms with susceptibility to ODD in a Han Chinese school population. METHODS: Four polymorphisms (rs4570625, rs11178997, rs1386494 and rs7305115) of the TPH-2 gene were analyzed by using polymerase chain reaction and DNA microarray hybridization in a case-control study of 276 Han Chinese individuals (124 ODD and 152 controls). RESULTS: In single marker analyses,there was a significant difference in the genotype (χ 2  = 4.163, P = 0.041) and allele frequency (χ 2  = 3.930, P = 0.047) of rs1386494 between ODD and control groups. Haplotype analyses revealed higher frequencies of haplotypes TA (rs4570625-rs11178997), TAG (rs4570625-rs11178997-rs1386494), TAA (rs4570625-rs11178997-rs7305115) and TAGA (rs4570625-rs11178997-rs1386494-rs7305115), but lower frequencies of haplotypes GA (rs4570625-rs11178997) and GAG (rs4570625-rs11178997-rs1386494) in ODD compared to control groups. CONCLUSIONS: These findings suggest the role of these TPH-2 gene variants in susceptibility to ODD. Some haplotypes might be the risk factors for Chinese Han children with ODD, while others might be preventable factors.

Lipocalin 2 promotes the migration and invasion of esophageal squamous cell carcinoma cells through a novel positive feedback loop.

Lipocalin 2 (LCN2) is a poor prognostic factor in esophageal squamous cell carcinoma (ESCC), however its functional roles and molecular mechanisms of action remain to be clarified. Here, we described the functions and signaling pathways for LCN2 in ESCC. Overexpression of LCN2 in ESCC cells accelerated cell migration and invasion in vitro, and promoted lung metastasis in vivo. Blocking LCN2 expression inhibited its pro-oncogenic effect. Either overexpression of LCN2 or treatment with recombinant human LCN2 protein enhanced the activation of MEK/ERK pathway, which in turn increases endogenous LCN2 to increase MMP-9 activity. The decreased p-cofilin and increased p-ERM induced by pERK1/2 cause the cytoskeleton F-actin rearrangement and alter the behavior of ESCC cells mediated by LCN2. As a consequence, activation of MMP-9 and the rearrangement of F-actin throw light on the mechanisms for LCN2 in ESCC. These results imply that LCN2 promotes the migration and invasion of ESCC cells through a novel positive feedback loop.

Macrolide analog F806 suppresses esophageal squamous cell carcinoma (ESCC) by blocking ß1 integrin activation.

The paucity of new drugs for the treatment of esophageal squamous cell carcinoma (ESCC) limits the treatment options. This study characterized the therapeutic efficacy and action mechanism of a novel natural macrolide compound F806 in human ESCC xenograft models and cell lines. F806 inhibited growth of ESCC, most importantly, it displayed fewer undesirable side effects on normal tissues in two human ESCC xenograft models. F806 inhibited proliferation of six ESCC cells lines, with the half maximal inhibitory concentration (IC50) ranging from 9.31 to 16.43 µM. Furthermore, F806 induced apoptosis of ESCC cells, contributing to its growth-inhibitory effect. Also, F806 inhibited cell adhesion resulting in anoikis. Mechanistic studies revealed that F806 inhibited the activation of ß1 integrin in part by binding to a novel site Arg610 of ß1 integrin, suppressed focal adhesion formation, decreased cell adhesion to extracellular matrix and eventually triggered apoptosis. We concluded that F806 would potentially be a well-tolerated anticancer drug by targeting ß1 integrin, resulting in anoikis in ESCC cells.

Prognostic value of serum α-fetoprotein in ovarian yolk sac tumors: A systematic review and meta-analysis.

This study was conducted to determine the prognostic value of serum α-fetoprotein (AFP) levels in patients with ovarian yolk sac tumor (OYST). We performed a systematic review and meta-analysis to assess the associations between serum AFP level and prognosis in OYST. A total of 12 quantitative studies met the inclusion criteria. Preoperative AFP was not found to be associated with overall survival (OS) [odds ratio (OR)=0.84, 95% confidence interval (CI): 0.43-1.62] in OYST. However, a high postoperative AFP level was associated with worse OS (OR=0.16, 95% CI: 0.05-0.48) and relapse-free survival (RFS) (OR=0.18, 95% CI: 0.08-0.43) compared to a low postoperative AFP level in patients with OYST. In addition, a postoperative AFP level of >1,000 ng/ml was associated with a decrease in OS (OR=0.16, 95% CI: 0.05-0.50) and RFS (OR=0.21, 95% CI: 0.08-0.57). In conclusion, the postoperative, but not the preoperative, AFP level was found to be a prognostic factor in patients with OYST. In particular, a postoperative AFP level of >1,000 ng/ml was an indicator of poor prognosis in patients with OYST.