Value of circulating tumor cell assisting low-dose computed tomography in screening pulmonary nodules based on existing liquid biopsy techniques: a systematic review with meta-analysis and trial sequential analysis.

OBJECTIVE: This study aims to assess the diagnostic utility of circulating tumor cells (CTCs) in conjunction with low-dose computed tomography (LDCT) for differentiating between benign and malignant pulmonary nodules and to substantiate the foundation for their integration into clinical practice. METHODS: A systematic literature review was performed independently by two researchers utilizing databases including PubMed, Web of Science, The Cochrane Library, Embase, and Medline, to collate studies up to September 15, 2023, that investigated the application of CTCs in diagnosing pulmonary nodules. A meta-analysis was executed employing Stata 15.0 and Revman 5.4 to calculate the pooled sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR), and the area under the receiver operating characteristic curve (AUC). Additionally, trial sequential analysis was conducted using dedicated TSA software. RESULTS: The selection criteria identified 16 studies, encompassing a total of 3409 patients. The meta-analysis revealed that CTCs achieved a pooled sensitivity of 0.84 (95% CI 0.80 to 0.87), specificity of 0.80 (95% CI 0.73 to 0.86), PLR of 4.23 (95% CI 3.12 to 5.72), NLR of 0.20 (95% CI 0.16 to 0.25), DOR of 20.92 (95% CI 13.52 to 32.36), and AUC of 0.89 (95% CI 0.86 to 0.93). CONCLUSIONS: Circulating tumor cells demonstrate substantial diagnostic accuracy in distinguishing benign from malignant pulmonary nodules. The incorporation of CTCs into the diagnostic protocol can significantly augment the diagnostic efficacy of LDCT in screening for malignant lung diseases.

A mechanism linking ferroptosis and ferritinophagy in melatonin-related improvement of diabetic brain injury.

Ferroptosis and ferritinophagy play critical roles in various disease contexts. Herein, we observed that ferroptosis and ferritinophagy were induced both in the brains of mice with diabetes mellitus (DM) and neuronal cells after high glucose (HG) treatment, as evidenced by decreases in GPX4, SLC7A11, and ferritin levels, but increases in NCOA4 levels. Interestingly, melatonin administration ameliorated neuronal damage by inhibiting ferroptosis and ferritinophagy both in vivo and in vitro. At the molecular level, we found that not only the ferroptosis inducer p53 but also the ferritinophagy mediator NCOA4 was the potential target of miR-214-3p, which was downregulated by DM status or HG insult, but was increased after melatonin treatment. However, the inhibitory effects of melatonin on ferroptosis and ferritinophagy were blocked by miR-214-3p downregulation. These findings suggest that melatonin is a potential drug for improving diabetic brain damage by inhibiting p53-mediated ferroptosis and NCOA4-mediated ferritinophagy through regulating miR-214-3p in neurons.

FOXD2-AS1 acts an oncogene in esophageal squamous cell carcinoma through sponging miR-204-3p

Purpose: A growing number of evidences has revealed that long non-coding RNAs (lncRNAs) have vital effect in the pathogenesis of esophageal squamous cell carcinoma (ESCC). In our work, we found that lncRNA FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) was significantly increased in clinical ESCC samples and cell lines.MethodsThe biological effect of FOXD2-AS1 on EC109 and KYSE150 cells showed that the low expression of FOXD2-AS1 inhibited the proliferation through CCK8 and colony formation assays, invasion by transwell chamber test, migration abilities by wound healing assay, and enhance apoptosis rates by flow cytometry assay.ResultsThrough bioinformatics analysis and luciferase reporter assays, microRNA (miR)-204-3p was proved to be a target of FOXD2-AS1. We further confirmed that FOXD2-AS1 was the upstream inhibitor of miR-204-3p and the down-regulation of miR-204-3p reversed the repressive effects of low expression of FOXD2-AS1 on ESCC progression. In addition, inhibition of FOXD2-AS1 effectively suppressed the tumor growth.ConclusionsIn general, our results suggested that FOXD2-AS1 may be of vital therapeutic importance for the treatment of ESCC patients. (AU)

FOXD2-AS1 acts an oncogene in esophageal squamous cell carcinoma through sponging miR-204-3p.

PURPOSE: A growing number of evidences has revealed that long non-coding RNAs (lncRNAs) have vital effect in the pathogenesis of esophageal squamous cell carcinoma (ESCC). In our work, we found that lncRNA FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) was significantly increased in clinical ESCC samples and cell lines. METHODS: The biological effect of FOXD2-AS1 on EC109 and KYSE150 cells showed that the low expression of FOXD2-AS1 inhibited the proliferation through CCK8 and colony formation assays, invasion by transwell chamber test, migration abilities by wound healing assay, and enhance apoptosis rates by flow cytometry assay. RESULTS: Through bioinformatics analysis and luciferase reporter assays, microRNA (miR)-204-3p was proved to be a target of FOXD2-AS1. We further confirmed that FOXD2-AS1 was the upstream inhibitor of miR-204-3p and the down-regulation of miR-204-3p reversed the repressive effects of low expression of FOXD2-AS1 on ESCC progression. In addition, inhibition of FOXD2-AS1 effectively suppressed the tumor growth. CONCLUSIONS: In general, our results suggested that FOXD2-AS1 may be of vital therapeutic importance for the treatment of ESCC patients.

Compound Heterozygous COX20 Variants Impair the Function of Mitochondrial Complex IV to Cause a Syndrome Involving Ophthalmoplegia and Visual Failure.

The cytochrome c oxidase 20 (COX20) gene encodes a protein with a crucial role in the assembly of mitochondrial complex IV (CIV). Mutations in this gene can result in ataxia and muscle hypotonia. However, ophthalmoplegia and visual failure associated with COX20 mutation have not been examined previously. Moreover, the mechanism causing the phenotype of patients with COX20 variants to differ from that of patients with mutations in other genes impairing CIV assembly is unclear. In this investigation, the aim was to assess the relation between COX20 variants and CIV assembly. We performed detailed clinical, physical, and biochemical investigations of affected individuals. Western blotting, reverse transcription-polymerase chain reaction, and blue native-polyacrylamide gel electrophoresis were used to analyze the expression level of COX20 and oxidative phosphorylation. A Seahorse XF Cell Mito Stress Test and enzymatic activity analysis were performed to evaluate mitochondrial function. Whole-exome sequencing revealed the same compound heterozygous mutations (c.41A > G and c.222G > T, NM_198076) in COX20 in two siblings. This is the first description of ophthalmoplegia and visual failure associated with COX20 variants. In vitro analysis confirmed that the COX20 protein level was significantly decreased, impairing the assembly and activity of CIV in patients' fibroblast. Overexpression of COX20 using a transduced adenovirus partially restored the function of the patients' fibroblasts. Early-onset complex movement disorders may be closely related to COX20 variants. Our results broaden the clinical phenotypes of patients with COX20 variants showing ophthalmoplegia and visual failure. Additionally, dysfunction of COX20 protein can impair the assembly and activity of CIV.

Growth Differentiation Factor 15 Protects SH-SY5Y Cells From Rotenone-Induced Toxicity by Suppressing Mitochondrial Apoptosis.

Objective: Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide. Mitochondrial dysfunction is suspected as one of the pathogenic mechanisms of PD. Growth/differentiation Factor-15 (GDF15) has been reported to affect mitochondrial function in PD. However, the relationship between mitochondrial function and GDF15 induction has not been explained well. Hence, we aimed to reveal the effect of GDF15 induction on SH-SY5Y cells with rotenone toxicity, a cell model of PD. Methods: SH-SY5Y cells were exposed to 1 µM rotenone as a PD model. Cells were transfected with a GDF15-overexpression plasmid and empty vector. We then analyzed the expression level of GDF15, BCL-2/BAX, P53, PGC1-α, α-syn, and TH in GDF15-overexpressing cells by western blotting, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction. The cytotoxicity of rotenone was measured by CCK-8 assays. Cell apoptosis was detected by flow cytometric and TUNEL assays. The effect of GDF15 on oxidative stress and mitochondrial function was revealed using DCFH-DA, mito-SOX, and JC-10 assays and a Seahorse XF Cell Mito Stress Test. Results: GDF15 protected rotenone-treated SH-SY5Y cells from toxicity by preserving mitochondrial function and decreasing apoptosis, during which GDF15 might function by influencing PGC1α through the regulation of p53. In addition, GDF15 overexpression could improve Akt and mTOR phosphorylation, leading to PI3K/Akt/mTOR pathway activation. However, these protective effects were eliminated when cells were treated with the PI3K/Akt specific inhibitor LY294002. Conclusion: Our findings suggest that GDF15 can protect mitochondrial function and inhibit apoptosis in SH-SY5Y cells after exposure to rotenone by upregulating PGC1α via p53. These properties might comprise its anti-apoptotic effects, mediated by the PI3K/Akt/mTOR signaling pathway.

Orthostatic tremor secondary to primary malignant melanoma of the spinal cord: A case report.

BACKGROUND AND PURPOSE: Orthostatic tremor and spinal cord melanoma are rare entities and seem unlikely to be associated. Herein, we report a patient diagnosed with orthostatic tremor secondary to primary malignant melanoma of the spinal cord. CASE PRESENTATION: We report the case of a 67-year-old man who experienced tremor when he was standing, which disappeared when he was sitting or walking. He also reported gait disturbance and cognitive dysfunction. Electromyography revealed a regular and symmetric high-frequency tremor in the lower extremities. The patient was admitted to a hospital several times and was diagnosed with primary orthostatic tremor and later hydrocephalus; thus, he received a ventriculoperitoneal shunt. Finally, he showed symptoms of the presence of melanoma in the spinal cord, which was supported by spinal cord magnetic resonance imaging findings. Primary malignant melanoma of the spinal cord was confirmed postoperatively. CONCLUSIONS: Orthostatic tremor is a rare entity that can be characterized by specific high-frequency tremors when the subject is standing. Considering that it remains unknown why this condition appears, some possible associations, such as primary spinal cord melanoma, should be considered. Thus, a comprehensive assessment of these types of patients is required. Our case report may facilitate the understanding of the pathophysiology and clinical symptoms of this disease.

Alteration and the Function of Intestinal Microbiota in High-Fat-Diet- or Genetics-Induced Lipid Accumulation.

Diet and host genetics influence the composition of intestinal microbiota, yet few studies have compared the function of intestinal microbiota in the diet- or genotype-induced lipid deposition, which limits our understanding of the role of intestinal bacteria in metabolic disorders. The lipid accumulation in wild-type zebrafish fed with control (CON) or high-fat (HF) diet and two gene-knockout zebrafish lines (cpt1b -/- or pparab -/-) fed with control diet was measured after a 4-week feeding experiment. The intestinal microbiota composition of these groups was investigated using 16S ribosomal RNA (rRNA) gene sequencing (DNA-based) and 16S rRNA sequencing (RNA-based). The HF diet or deficiency of two genes induced more weight gain and higher triglyceride content in the liver compared with their control group. 16S rRNA gene sequencing (DNA-based) indicated the decreased abundance of Proteobacteria in the HF group compared with CON, but there was no significant difference in bacterial α diversity among treatments. 16S rRNA sequencing (RNA-based) confirmed the decreased abundance of Proteobacteria and the bacterial α diversity in the HF group compared with CON. Deficiency of cpt1b or pparab showed less change in microbiota composition compared with their wild-type group. Intestinal microbiota of each group was transferred to germ-free zebrafish, and the quantification of Nile red staining indicated that the intestinal microbiota of the HF group induced more lipid accumulation compared with CON, whereas intestinal microbiota of cpt1b -/- and pparab -/- zebrafish did not. The results showed that RNA-based bacterial sequencing revealed more bacterial alteration than DNA-based bacterial sequencing. HF diet had a more dominant role in shaping gut microbiota composition to induce lipid accumulation compared with the gene-knockout of cpt1b or pparab in zebrafish, and the transplant of intestinal microbiota from HF-fed fish induced more lipid deposition in germ-free zebrafish. Together, these data suggested that a high-fat diet exerted a more dominant role over the deletion of cpt1b or pparab on the intestinal bacterial composition, which corresponded to lipid accumulation.

The efficacy and safety of antiepileptics in the prophylaxis of pediatric migraine: the meta-analysis of randomized controlled trials.

BACKGROUND: Migraine is the most common primary headache among children and adolescents. The aim of this meta-analysis was to evaluate the efficacy and safety of antiepileptic drugs in the prevention of pediatric migraine. METHODS: PubMed, Cochrane Library, EMBASE and Chinese National Knowledge Infrastructure (CNKI) databases were searched for eligible published RCTs from January 1970 to June 2020. Migraine frequency and ≥50% response rate were measured as the efficacy outcomes. We used "Risk of Bias" tool for quality assessment and RevMan5.3 software for statistical analysis. RESULTS: Four articles containing 7 RCTs with 794 participants compared the efficacy of AEDs with placebo. Four RCTs assessed topiramate vs. placebo and 3 RCTs evaluated divalproex sodium extended-release (DVPX ER) vs. placebo. The results demonstrated that children receiving antiepileptic drugs had a significant advantage in remitting the mean monthly migraine days compared to those who received placebo, with an MD of -0.48 (n=930, 95% CI: -0.84 to -0.12, Z=2.60, P=0.009). Topiramate significantly reduced monthly migraine days (MD =-0.70, n=489, 95% CI: -1.16 to -0.25, Z=3.01, P=0.003) but failed to improve the ≥50% response rate (MD =-1.50, n=489, 95% CI: 0.70 to 3.22, Z=1.05, P=0.30). DVPX ER did not significantly reduce monthly headache frequency (n=441, 95% CI: -0.70 to 0.47, Z=0.38, P=0.70) or improve the ≥50% response rate (n=441, 95% CI: 0.59 to 1.25, Z=0.82, P=0.41) compared with placebo. Topiramate and DVPX ER were related to higher rates of side effects and adverse reactions. DISCUSSION: Topiramate can reduce monthly headache days in children and adolescents with migraine. However, it failed to improve the ≥50% response rate. DVPX ER showed no difference from placebo in the prophylactic treatment pediatric migraine. Side effects seemed to be more frequent in topiramate and DVPX ER treated children but generally well-tolerated.

Whether cognitive behavioral therapy is effective for Alzheimer's disease: A protocol for systematic review and network meta-analysis.

BACKGROUND: Alzheimer disease (AD) is a progressive neurodegenerative disease characterized by impaired memory and cognitive judgment. It is the leading cause of dementia in the elderly, and its high morbidity and mortality have also brought a significant social burden. So far, there is no method can completely cure Alzheimer's dementia, but there are many non-drug treatments that have been praised by people, especially the cognitive behavioral therapy proposed in recent years. The main purpose of this article is to evaluate the effect of cognitive behavioral therapy on the cognitive function improvement of patients with Alzheimer's dementia. METHODS: We did a network meta-analysis to identify both direct and indirect evidence in relevant studies. A systematic literature search will be performed in the Cochrane Library, PubMed, and EMBASE from inception to October 2020. We extracted the relevant information from these trials with a predefined data extraction sheet and assessed the risk of bias with the Cochrane risk of bias tool.The outcomes investigated were Mini-Mental State Examination and AD Assessment Scale-Cognitive section scores. We did a pair-wise meta-analysis using the fixed-effects model and then did a random-effects network meta-analysis within a Bayesian framework. The = the Assessment of Multiple Systematic Reviews-2 scale, Preferred Reporting Items for Systematic Reviews and Meta-Analyses scale and Grading of Recommendations Assessment, Development and Evaluation were used to assess the quality and evidence grade of the literature. General characteristics of the eligible randomized controlled trials will be summarized and described. Meanwhile, The ADDIS software will be used to perform the network meta-analysis, and the result figures will be generated by STATA 15.0 software. RESULTS: Using the draft search strategy of databases and after screening,7 randomized controlled trials met the a priori criteria and were included. This network mate-analysis will be published in a peer-reviewed journal. CONCLUSION: Our study will provide evidence for cognitive behavioral intervention in AD patients. And provide recommendations and guidelines for the clinic. PROTOCOL REGISTRATION: INPLASY2020110052.

The individual and combined effects of hypoxia and high-fat diet feeding on nutrient composition and flesh quality in Nile tilapia (Oreochromis niloticus).

Hypoxia and high-fat diet (HFD) feeding are two factors commonly existing in aquaculture. However, their individual and combined effects on nutrient composition and flesh quality in fish have not been investigated. The present study evaluated the alterations of growth, nutrient composition and flesh quality in Nile tilapia (initially 7.0 ± 0.1 g and 5.6 ± 0.2 cm) fed with normal fat diet (5.95% fat) or HFD (11.8% fat) at two dissolved oxygen levels (1.1 ± 0.1 and 7.2 ± 0.1 mg/L) for 8 weeks. The results showed that hypoxia and HFD had similar effects in inducing lipid deposition, reducing flesh protein and amino acids content, pH values and water holding ability. Hypoxia had additional adverse effects in decreasing meat yield, flesh contents of n-3 PUFA and glycogen, increasing flesh fragmentation and causing liver damages. The combination of hypoxia and HFD significantly decreased feed intake, survival rate and muscle protein content, but didn't affect flesh quality-related parameters.

Oligosaccharides improve the flesh quality and nutrition value of Nile tilapia fed with high carbohydrate diet.

High level of carbohydrate in aquafeed could achieve cost-sparing effect, but it may cause adverse effects on flesh quality of aquatic products. An eight-week trial was conducted to investigate whether oligosaccharides-supplementation, including Galacto-oligosaccharides (GOS) and xylo-oligosaccharide (XOS), could systematically improve the growth performance, texture characteristics and nutrition composition of Nile tilapia fed with high-carbohydrate diet. The results indicated that GOS-supplementation improved the amino acid composition, while XOS-supplementation showed beneficial effects on growth performance. High-carbohydrate diet had adverse effects on fillet texture, while oligosaccharide-supplementation regulated the expression of muscle development-related genes to help restoring muscle texture properties. Furthermore, either high-carbohydrate or addition of oligosaccharides could change the intestinal microbiota composition and their metabolites. Further correlation analysis suggested that intestinal microbiota may account for the improvement in fish growth condition and texture characteristics. Application of oligosaccharides may be an innovative strategy for flesh quality modulation in aquaculture.

Peroxisomal proliferator-activated receptor α-b deficiency induces the reprogramming of nutrient metabolism in zebrafish.

KEY POINTS: The pparab subtype in zebrafish is much more highly expressed in tissues with high oxidative activity than pparaa. The pparab deficiency in zebrafish reduces fatty acid ß-oxidation both in liver and muscle, illustrating its functional homology as a mammalian peroxisome proliferator-activated receptor α (PPARα). pparab deficiency promotes metabolic reprogramming by increasing glucose utilization and inhibiting amino acid breakdown. The present study brings new insights into the comprehensive regulatory roles of PPARα in the cellular fuel selection and provides a valuable animal model for PPARα studies from a viewpoint of comparative physiology. ABSTRACT: Dysfunction of lipid metabolism is involved in the pathogenesis of several chronic metabolic diseases. Peroxisome proliferator-activated receptor α (PPARα) is essential for normal metabolic homeostasis and, in particular, for the regulation of fatty acid ß-oxidation (FAO). However, little is known about its regulation roles in systemic nutrient metabolism. To explore the underlying modulation role of PPARα in metabolic homeostasis, we generated a pparab-knockout zebrafish (Danio rerio) model. The pparab mutants demonstrated lower expression of key enzymes involved in FAO, as well as lower mitochondrial and peroxisomal FAO in tissues, which was associated with lipid accumulation in liver and visceral mass. Conversely, glucose utilization was higher because they demonstrated lower blood glucose and tissue glycogen concentrations, as well as activation of the phosphoinositide 3-kinase/AKT pathway. In addition, pparab-deficient zebrafish demonstrated activation of AKT/mammalian target of rapamycin signalling and higher protein content, implying greater protein synthesis and/or lower amino acid breakdown. These data clearly revealed that pparab deletion reduces FAO but increases glucose utilization and protein deposition to maintain energy homeostasis. The present study provides new insights into the comprehensive regulatory role of PPARα in systemic energy metabolism in fish, and this pparab-deficient zebrafish also constitutes a valuable model for investigating the functions of PPARα in mammals from comparative physiology aspects.

Environmental estrogen exposure converts lipid metabolism in male fish to a female pattern mediated by AMPK and mTOR signaling pathways.

Environmental estrogens, including bisphenol A (BPA) and 17ß-estradiol (E2), which are widely used in industries and medicine, pose a severe ecological threat to fish due to feminization induction. However, the related metabolic basis for reproductive feminization in male fish has not been well addressed. We first found that female zebrafish exhibited higher lipid accumulation and lipogenesis activity than males. Next, we exposed male and female zebrafish to E2 (200 ng/L) or BPA (100 µg/L) for six weeks, and observed an early-phase reproductive feminization in males, accompanied with reduced spermatids, significant fat deposition and lipogenic gene expressions that mimicked female patterns. Cellular signaling assays revealed that, E2 or BPA modulated lipid metabolism in males mainly through lowering 5' AMP-activated protein kinase (AMPK) and upregulating the lipogenic mechanistic target of rapamycin (mTOR) pathways. For the first time, we show that environmental estrogens could alter lipid metabolism in male fish to a female pattern (metabolic feminization) prior to gonad feminization in male fish, to allows males to accumulate efficiently lipids to harmonize with the feminized gonads. This study suggests that negative effects of environmental estrogens, as hazardous materials, on vertebrate health are more complicated than originally thought.

Up-Regulation of MicroRNA-21 Indicates Poor Prognosis and Promotes Cell Proliferation in Esophageal Squamous Cell Carcinoma via Upregulation of lncRNA SNHG1.

INTRODUCTION: MicroRNA-21 (miRNA-21) and lncRNA SNHG1 (small nucleolar RNA host gene 1) are known to be aberrantly upregulated and promote tumor progression in various cancers. Nevertheless, very few studies have determined the roles of tissue and circulating miRNA-21 and SNHG1 in ESCC patients. Particularly, knowledge about the characteristics of miRNA-21 and SNHG1 expression and their correlations with survival rates, as well as their interaction with each other remains inadequate in ESCC. METHODS: Thse expression level of miRNA-21 and SNHG1 of tissues, serum and cell lines were detected by qRT-PCR, and the characteristics of their expression and clinicopathology were analyzed. Then, the diagnostic and prognosis value of serum and tissue miRNA-21 and SNHG1 were evaluated, respectively. In addition, the interaction with each other between miRNA-21 and SNHG1, as well as the effect on ESCC cell proliferation were further clarified. RESULTS: The expression level of miRNA-21 and SNHG1 are significantly upregulated in tissues, serum and cell lines of ESCC, and tissue miRNA-21 and SNHG1 significantly correlates with lymph node metastasis, TNM stage, tumor size, and poor overall survival in ESCC patients. The receiver operating characteristic (ROC) curves show that areas under the ROC curve (AUC) for serum miRNA-21 and SNHG1 are 0.928 and 0.850, respectively. Pearson correlation coefficient indicated that the expression levels of miRNA-21 and SNHG1 in frozen cancerous tissues are significantly associated with their respective serum levels. Further, Cox univariate and multivariate analyses reveal that miRNA-21 and SNHG1 are independent prognostic factors for overall survival (OS) and disease-free survival (DFS) in ESCC patients. In addition, our in vitro data revealed a novel regulatory pathway, in which miRNA-21 is probably a unidirectional upstream positive regulator of SNHG1 in ESCC cells, and the interaction between miRNA-21 and SNHG1 plays an important role in the proliferation of ESCC cells. DISCUSSION: In summary, our data show that SNHG1 may be a novel downstream target of miRNA-21 and not vice versa in ESCC cells and contributes significantly toward the proliferation of ESCC cells. These findings suggest that miRNA-21 and SNHG1 may serve as potential diagnostic, prognostic biomarkers and therapeutic targets for ESCC patients.

PPARα activation enhances the ability of nile tilapia (Oreochromis niloticus) to resist Aeromonas hydrophila infection.

Peroxisome proliferator-activated receptor α (PPARα) plays critical physiological roles in energy metabolism, antioxidation and immunity of mammals, however, these functions have not been fully understood in fish. In the present study, Nile tilapia (Oreochromis niloticus) were fed with fenofibrate, an agonist of PPARα, for six weeks, and subsequently challenged with Aeromonas hydrophila. The results showed that PPARα was efficiently activated by fenofibrate through increasing mRNA and protein expressions and protein dephosphorylation. PPARα activation increased significantly mitochondrial fatty acid ß-oxidation efficiency, the copy number of mitochondrial DNA and expression of monoamine oxidase (MAO), a marker gene of mitochondria. Meanwhile, PPARα activation also increased significantly the expression of NADH dehydrogenase [ubiquinone] 1α subcomplex subunit 9 (NDUFA9, complex I) and mitochondrial cytochrome c oxidase 1 (MTCO1, complex IV). The fenofibrate-fed fish had higher survival rate when exposed to A. hydrophila. Moreover, the fenofibrate-fed fish also had higher activities of immune and antioxidative enzymes, and gene expressions of anti-inflammatory cytokines, while had lower expressions of pro-inflammatory cytokine genes. Taken together, PPARα activation improved the ability of Nile tilapia to resist A. hydrophila, mainly through enhancing mitochondrial fatty acids ß-oxidation, immune and antioxidant capacities, as well as inhibiting inflammation. This is the first study showing the regulatory effects of PPARα activation on immune functions through increasing mitochondria-mediated energy supply in fish.

The comparisons in protective mechanisms and efficiencies among dietary α-lipoic acid, ß-glucan and l-carnitine on Nile tilapia infected by Aeromonas hydrophila.

Dietary α-lipoic acid (LA), ß-glucan (Gluc) and l-carnitine (L-Ca) are commonly used additives to promote fish growth and stress resistance in aquaculture production. However their mechanisms and efficiencies in helping fish to resist diseases have not been compared before. In this study, we fed Nile tilapia (Oreochromis niloticus) with diets containing appropriate doses of LA, Gluc and L-Ca for five weeks and further intraperitoneally injected the fish with Aeromonas hydrophila. After dietary treatment, none of the additives affected the fish growth, but dietary Gluc and L-Ca reduced protein and lipid body contents in fish, respectively. After A. hydrophila challenge, all fish treated with the three dietary additives showed higher survival rate, but those fed on dietary L-Ca had lower survival than those fed on LA and Gluc diets, indicating high protection efficiency of LA and Gluc. The protective mechanisms of the three feed additives were quite different under A. hydrophila infection. Dietary LA induced higher total antioxidant capacity and higher mRNA expression of anti-oxidative genes than other additives in liver and also activated partly the immune function in serum and spleen. Gluc largely increased the immune function by activating the immunity enzymes in serum, inducing inflammation in liver and increasing the expression of immune genes in spleen and head kidney. Gluc also increased partly the antioxidant capacity in serum and liver and lipid catabolism in liver. L-Ca largely increased lipid catabolism in liver while it increased partly the antioxidant capacities in serum and liver. Taken together, these results indicate that, dietary LA, Gluc and L-Ca have various protective mechanisms and differ in their efficiencies on resisting A. hydrophila infection in Nile tilapia.

Minimally invasive oesophagectomy versus open esophagectomy for resectable esophageal cancer: a meta-analysis.

BACKGROUND: Open esophagectomy (OE) is associated with significant morbidity and mortality. Minimally invasive oesophagectomy (MIO) reduces complications in resectable esophageal cancer. The aim of this study is to explore the superiority of MIO in reducing complications and in-hospital mortality than OE. METHODS: MEDLINE, Embase, Science Citation Index, Wanfang, and Wiley Online Library were thoroughly searched. Odds ratio (OR)/weighted mean difference (WMD) with a 95% confidence interval (CI) was used to assess the strength of association. RESULTS: Fifty-seven studies containing 15,790 cases of resectable esophageal cancer were included. MIO had less intraoperative blood loss, short hospital stay, and high operative time (P < 0.05) than OE. MIO also had reduced incidence of total complications; (OR = 0.700, 95% CI = 0.626 ~ 0.781, P V < 0.05), pulmonary complications (OR = 0.527, 95% CI = 0431 ~ 0.645, P V < 0.05), cardiovascular complications (OR = 0.770, 95% CI = 0.681 ~ 0.872, P V < 0.05), and surgical technology related (STR) complications (OR = 0.639, 95% CI = 0.522 ~ 0.781, P V < 0.05), as well as lower in-hospital mortality (OR = 0.668, 95% CI = 0.539 ~ 0.827, P V < 0.05). However, the number of harvested lymph nodes, intensive care unit (ICU) stay, gastrointestinal complications, anastomotic leak (AL), and recurrent laryngeal nerve palsy (RLNP) had no significant difference. CONCLUSIONS: MIO is superior to OE in terms of perioperative complications and in-hospital mortality.

Differential expression of miR-21 and miR-75 in esophageal carcinoma patients and its clinical implication.

In Xinjiang, China, esophageal carcinoma has a high incidence in Kazak and Uighur populations. MicroRNA (miR)-21 and miR-375 are related to esophageal carcinoma. This study thus investigated their potencials in early diagnosis and prognosis in Kazak and Uighur populations, to provide evidences for serum markers of esophageal cancer. A total of 126 Kazak or Uighur esophageal cancer patients were enrolled as the disease group, along with 86 local Han patients as disease control cohort, and 80 healthy Kazak or Uighur individuals. MiRNA expression was detected by in situ hybridization in tissues and by qRT-PCR in serum. ROC approach was used to evaluate the diagnostic value of miRNA on esophageal carcinoma. Cox analysis was performed to screen factors governing prognosis. MiR-21 level was significantly elevated in both tissue and serum samples of esophageal cancer patients, while miR-375 was down-regulated. Such difference was more potent in disease group compared to disease control group. MiR expression was correlated with infiltration depth, TNM stage, vascular invasion, and lymph node metastasis. Elevated expression of miR-21 reduced the sensitivity of radio-therapy, and increased recurrence frequency. The diagnostic value of single assay for miR-21 or miR-375 was lower than the combined assay (AUC=0.812 or 0.739 vs. 0.858). They also affected patient prognosis (OR=1.53 or 0.652). MiR-21 and miR-375 presented abnormal expression in Kazak or Uighur esophageal carcinoma patients and were independent factors affecting prognosis. The combined assay of miR-21 and miR-375 may help to make early diagnosis of esophageal cancer.