MiRNA-296-5p promotes the sensitivity of nasopharyngeal carcinoma cells to cisplatin via targeted inhibition of STAT3/KLF4 signaling axis.

Improving drug sensitivity is an important strategy in chemotherapy of cancer and accumulating evidence indicates that miRNAs are involved in the regulation of drug sensitivity, but the specific mechanism is still unclear. Our previous study has found that miR-296-5p was significantly downregulated in nasopharyngeal carcinoma (NPC). Here, we aim to explore whether miR-296-5p is involved in regulating cisplatin sensitivity in NPC by regulating STAT3/KLF4 signaling axis. The cell proliferation and clonogenic capacity of NPC cells were evaluated by CCK8 Assay and plate colony assay, respectively. The Annexin V-FITC staining kit was used to determine and quantify the apoptotic cells using flow cytometry. The drug efflux ability of NPC cells were determined by Rhodamine 123 efflux experiment. The expression of miR-296-5p, apoptosis-related genes and protein in NPC cell lines were detected by qPCR and Western blot, respectively. Animal study was used to evaluate the sensitivity of NPC cells to DDP treatment in vivo. Our results showed that elevated miR-296-5p expression obviously promoted the sensitivity of NPC cells to DDP by inhibiting cell proliferation and clonogenic capacity, and inducing apoptosis. In addition, we found that miR-296-5p inhibited the expression of STAT3 and KLF4 in NPC cells, while overexpression of exogenous STAT3 reversed miR-296-5p-mediated enhancement in cell death of DDP-treated NPC cells. In vivo studies further confirmed that miR-296-5p promotes the sensitivity of NPC cells to DDP treatment. miRNA-296-5p enhances the drug sensitivity of nasopharyngeal carcinoma cells to cisplatin via STAT3/KLF4 signaling pathway.

Surviving winter on the Qinghai-Xizang Plateau: Extensive reversible protein phosphorylation plays a dominant role in regulating hypometabolism in hibernating Nanorana parkeri.

Changes in protein abundance and reversible protein phosphorylation (RPP) play important roles in regulating hypometabolism but have never been documented in overwintering frogs at high altitudes. To test the hypothesis that protein abundance and phosphorylation change in response to winter hibernation, we conducted a comprehensive and quantitative proteomic and phosphoproteomic analysis of the liver of the Xizang plateau frog, Nanorana parkeri, living on the Qinghai-Xizang (Tibet) Plateau (QTP). In total, 5 170 proteins and 5 695 phosphorylation sites in 1 938 proteins were quantified. Based on proteomic analysis, 674 differentially expressed proteins (438 up-regulated, 236 down-regulated) were screened in hibernating N. parkeri versus summer individuals. Functional enrichment analysis revealed that higher expressed proteins in winter were significantly enriched in immune-related signaling pathways, whereas lower expressed proteins were mainly involved in metabolic processes. A total of 4 251 modified sites (4 147 up-regulated, 104 down-regulated) belonging to 1 638 phosphoproteins (1 555 up-regulated, 83 down-regulated) were significantly changed in the liver. During hibernation, RPP regulated a diverse array of proteins involved in multiple functions, including metabolic enzymatic activity, ion transport, protein turnover, signal transduction, and alternative splicing. These changes contribute to enhancing protection, suppressing energy-consuming processes, and inducing metabolic depression. Moreover, the activities of phosphofructokinase, glutamate dehydrogenase, and ATPase were all significantly lower in winter compared to summer. In conclusion, our results support the hypothesis and demonstrate the importance of RPP as a regulatory mechanism when animals transition into a hypometabolic state.

DHA inhibits invasion and metastasis in NSCLC cells by interfering with CCL18/STAT3 signaling pathway.

Omega-3 has been proposed as an antitumor substance that suppresses the growth and metastasis of multiple types of tumor cells, including lung cancer, but the specific mechanisms involved remain obscure. Our previous studies showed that the expression of chemokine ligand 18 was related to the migration and metastasis of non-small cell lung cancer. Here, we aim to explore whether omega-3 inhibits invasion and metastasis of NSCLC by regulating the expression of CCL18. The expression of CCL18, metastasis- and epithelial-mesenchymal transition (EMT)-related genes at mRNA and protein levels in NSCLC cell lines were detected by RT-qPCR and Western blot, respectively. The metastatic and invasive capability of NSCLC cells were evaluated by scratch wound healing and Transwell assays, respectively. Our results showed that the level of CCL18 is positively associated with metastatic ability of NSCLC cells. Docosahexaenoic acid, an important long-chain, polyunsaturated omega-3 (n-3) fatty acid, significantly inhibited invasion and metastasis of NSCLC cells, and concomitantly downregulated the expression of metastasis- and EMT-related genes and p-STAT3 signaling pathway. Additionally, we found that DHA inhibited CCL18 expression in lung cancer cells, while overexpression of CCL18 effectively reversed DHA-mediated downregulation in the expression of metastasis- and EMT-related genes and p-STAT3 signaling as well as DHA-mediated inhibitory effect on metastasis and invasion of NSCLC cells. DHA inhibits NSCLC cell invasion and metastasis possibly through targeted inhibition of CCL18/ STAT3 signaling pathway and EMT process.

Omega-3 Polyunsaturated Fatty Acids Protect against High-Fat Diet-Induced Morphological and Functional Impairments of Brown Fat in Transgenic Fat-1 Mice.

The role of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in the regulation of energy homeostasis remains poorly understood. In this study, we used a transgenic fat-1 mouse model, which can produce n-3 PUFAs endogenously, to investigate how n-3 PUFAs regulate the morphology and function of brown adipose tissue (BAT). We found that high-fat diet (HFD) induced a remarkable morphological change in BAT, characterized by "whitening" due to large lipid droplet accumulation within BAT cells, associated with obesity in wild-type (WT) mice, whereas the changes in body fat mass and BAT morphology were significantly alleviated in fat-1 mice. The expression of thermogenic markers and lypolytic enzymes was significantly higher in fat-1 mice than that in WT mice fed with HFD. In addition, fat-1 mice had significantly lower levels of inflammatory markers in BAT and lipopolysaccharide (LPS) in plasma compared with WT mice. Furthermore, fat-1 mice were resistant to LPS-induced suppression of UCP1 and PGC-1 expression and lipid deposits in BAT. Our data has demonstrated that high-fat diet-induced obesity is associated with impairments of BAT morphology (whitening) and function, which can be ameliorated by elevated tissue status of n-3 PUFAs, possibly through suppressing the effects of LPS on inflammation and thermogenesis.

Decreased Tissue Omega-6/Omega-3 Fatty Acid Ratio Prevents Chemotherapy-Induced Gastrointestinal Toxicity Associated with Alterations of Gut Microbiome.

Gastrointestinal toxicity (GIT) is a debilitating side effect of Irinotecan (CPT-11) and limits its clinical utility. Gut dysbiosis has been shown to mediate this side effect of CPT-11 by increasing gut bacterial ß-glucuronidase (GUSB) activity and impairing the intestinal mucosal barrier (IMB). We have recently shown the opposing effects of omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) on the gut microbiome. We hypothesized that elevated levels of tissue n-3 PUFA with a decreased n-6/n-3 PUFA ratio would reduce CPT-11-induced GIT and associated changes in the gut microbiome. Using a unique transgenic mouse (FAT-1) model combined with dietary supplementation experiments, we demonstrate that an elevated tissue n-3 PUFA status with a decreased n-6/n-3 PUFA ratio significantly reduces CPT-11-induced weight loss, bloody diarrhea, gut pathological changes, and mortality. Gut microbiome analysis by 16S rRNA gene sequencing and QIIME2 revealed that improvements in GIT were associated with the reduction in the CPT-11-induced increase in both GUSB-producing bacteria (e.g., Enterobacteriaceae) and GUSB enzyme activity, decrease in IMB-maintaining bacteria (e.g., Bifidobacterium), IMB dysfunction and systemic endotoxemia. These results uncover a host-microbiome interaction approach to the management of drug-induced gut toxicity. The prevention of CPT-11-induced gut microbiome changes by decreasing the tissue n-6/n-3 PUFA ratio could be a novel strategy to prevent chemotherapy-induced GIT.

Prediction model for cardiovascular disease risk in hemodialysis patients.

PURPOSE: To derive and validate a prediction score for cardiovascular disease (CVD) risk in hemodialysis patients in China. METHODS: Three hundred and eighty-eight patients with regular hemodialysis for more than 3 months were recruited from January 1, 2015 to September 30, 2019 and followed up till May 31, 2020. We derived a prediction score using all participants as a training data set and validated using a bootstrap validation data set. Discriminatory ability of the prediction score was assessed by the area under the receiver operating characteristic curve (AUC). RESULTS: Of 388 patients without CVD at baseline, 132 developed first CVD events during an average follow-up of 3.27 (inter-quartile range = 3.08) years. Of 26 clinical parameters, age, hypertension, diabetes and abnormal white blood cell (WBC) count were identified as significant predictors and included in the prediction model. Compared to those without any of these risk factors, those with one, two, and three to four points showed increased risks of CVD, with the adjusted hazards ratio and 95% confidence interval (CI) being 3.29 (1.17-9.26), 7.42 (2.68-20.51) and 15.43 (5.44-43.75), respectively. The score showed satisfactory discriminatory ability in both training and validation data set (AUC = 0.7025, 95% CI 0.6520-0.7530, and 0.6876, 95% CI 0.6553-0.7200, respectively). CONCLUSION: We derived and validated a prediction score for CVD risk in hemodialysis patients in China. Given there is a rapid increase in the number of hemodialysis patients, this simple point score can be used to identify high-risk individuals in clinical practice for more precise and efficient personalized treatment.

Fish consumption, long-chain omega-3 fatty acids intake and risk of stroke: An updated systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Although fish consumption or omega-3 intake is associated with cardio- cerebrovascular disease including stroke, their correlation is still controversial. Therefore, this meta-analysis is to identify the relationship between the risk of stroke and fish consumption or omega-3 intake. METHODS AND STUDY DESIGN: We searched the PubMed, EMBASE and Cochrane Library databases as of May 2019. Multivariateadjusted risk ratios (RRs) with 95% confidence interval (CI) for stroke in different level intake of fish or Longchain omega-3 polyunsaturated fatty acids (LC ω3-PUFAs) were pooled using a random-effects meta-analysis. A dose-response analysis was conducted with the 2-stage generalized least-squares trend program. RESULTS: Our meta-analysis identified a total of 17 prospective cohort studies including 14986 strokes events in 672711 individuals. Meta-analysis revealed that the higher fish consumption was significantly associated with lower risk of stroke (RR=0.871, 95% CI: 0.779-0.975, p=0.016), especially with ischemic stroke (RR=0.808, 95% CI: 0.696- 0.937, p=0.005). Meantime, the combined RR of total stroke was 0.859 (95% CI: 0.769-0.959, p=0.007) for the highest versus lowest intake of LC ω3-PUFAs, and stratification analysis showed that higher LC ω3-PUFAs intake was associated with reduced stroke risk in women (RR=0.793, 95% CI: 0.706-0.891, p=0.000) but not in men. In addition, the dose-response analysis showed fish consumption with 1000g per month and LC ω3-PUFAs intake with 0.5g per month was associated with 17.3% (RR=0.927, 95% CI: 0.83-0.98) and 14% (RR=0.86, 95% CI: 0.78-0.95) lower risk of stroke, respectively. CONCLUSIONS: Both fish consumption and LC ω3-PUFAs intake were negatively associated with the risk of stroke, especially in women, which suggest that increased intake of fishery products and LC ω3-PUFAs may benefit primary prevention of stroke.

Cloning and characterization of two chlorophyll A/B binding protein genes and analysis of their gene family in Camellia sinensis.

In this study, two chlorophyll A/B binding protein (CAB) genes (CsCP1 and CsCP2) in tea plant were cloned. The proteins encoded by these genes belong to the external or internal antenna proteins of PS II, respectively. They may be the targets of physiological regulation for tea leaf cell PS II because they all contain multiple functional domains and modifiable sites. The CAB gene family in the tea genome consists of 25 homologous genes. We measured the expression patterns of ten genes in the CsCP1 and CsCP2 subfamily under six different stresses. CsCP1 expression was inhibited in response to 6 kinds of stress; CsCP2 expression was slightly upregulated only after cold stress and ABA treatment. However, the expression levels of CSA016997 and CSA030476 were upregulated significantly in the six stresses. The results suggested that the 10 CAB genes may have different functions in tea leaves. Moreover, changes in the expression of the 10 genes under stress appear to be related to ABA- and MeJA-dependent signalling pathways, and their responses to MeJA treatment is faster than those to ABA. In addition, we introduced our experiences for cloning the genes in the context of complex genomes.

Dynamic prediction of liver cirrhosis risk in chronic hepatitis B patients using longitudinal clinical data.

OBJECTIVES: In longitudinal studies, serum biomarkers are often measured longitudinally which is valuable to predict the risk of disease progression. Previous risk prediction models for liver cirrhosis restrict data to baseline or baseline and a single follow-up time point, which failed to incorporate the time-dependent marker information. The aim of this study is to develop risk model in patients with chronic hepatitis B for dynamic prediction of cirrhosis by incorporating longitudinal clinical data. METHODS: Data from the hospital-based retrospective cohort at the Third Affiliated Hospital of Sun Yat-sen University, from 2004 to 2016, were analyzed. Using the multilevel logistic regression model, the time-dependent marker information and individual characteristics were taken as input, and the risk of at different time as the output. RESULTS: At the end of follow-up, 8.8% of patients progressed to cirrhosis, the average estimate values of hepatitis B virus DNA and alanine aminotransferase demonstrated a downward trend, the aspartate aminotransferase/alanine aminotransferase ratio showed a flat trend overall. The important predictors were as follows: age, oral antiviral treatment, hepatitis B virus DNA. This risk prediction model had an area under the receiver operator characteristic curve of 0.835 (95% confidence interval: 0.772-0.899) and 0.809 (95% confidence interval: 0.708-0.910) in the derivation and validation sets, respectively. CONCLUSION: Longitudinal prediction model can be used for dynamic prediction of disease progression and identify changing high-risk patients.

Multi-omic analysis in transgenic mice implicates omega-6/omega-3 fatty acid imbalance as a risk factor for chronic disease.

An unbalanced increase in dietary omega-6 (n-6) polyunsaturated fatty acids (PUFA) and decrease in omega-3 (n-3) PUFA in the Western diet coincides with the global rise in chronic diseases. Whether n-6 and n-3 PUFA oppositely contribute to the development of chronic disease remains controversial. By using transgenic mice capable of synthesizing PUFA to eliminate confounding factors of diet, we show here that alteration of the tissue n-6/n-3 PUFA ratio leads to correlated changes in the gut microbiome and fecal and serum metabolites. Transgenic mice able to overproduce n-6 PUFA and achieve a high tissue n-6/n-3 PUFA ratio exhibit an increased risk for metabolic diseases and cancer, whereas mice able to convert n-6 to n-3 PUFA, and that have a lower n-6/n-3 ratio, show healthy phenotypes. Our study demonstrates that n-6 PUFA may be harmful in excess and suggests the importance of a low tissue n-6/n-3 ratio in reducing the risk for chronic diseases.

Comparative analysis of mitochondrial DNA datasets indicates that Toxascaris leonina represents a species complex.

BACKGROUND: Toxascaris leonina is one of the most common intestinal parasites of canids and felids. In this study, we characterised the entire mitochondrial (mt) genome sequence of T. leonina from the cheetah and compared it with that of T. leonina from the dog. RESULTS: The entire mt genome sequence of T. leonina from the cheetah is 14,685 bp in size, which is 375 bp longer than that from the dog, and it is 408 bp longer than that from the South China tiger. The overall nucleotide sequence (except for the non-coding region) identity was 92.8% between the two mt genomes of T. leonina from the cheetah and the dog. For the 12 protein-coding genes, sequence difference between T. leonina from the cheetah and the dog was 5.0-9.7% at the nucleotide level and 1.0-7.2% at the amino acid level. Moreover, comparison of mt cox1 sequences among T. leonina isolates (n = 23) from different hosts revealed substantial nucleotide differences (10.6%). Phylogenetic analysis showed the separation of T. leonina from canid and felid hosts into three distinct clades. CONCLUSIONS: Taken together, these mtDNA datasets indicate that T. leonina from canid and felid hosts represents a species complex. Our results have implications for further studies of the molecular epidemiology, systematics and population genetics of this nematode.

The serum level of CC chemokine ligand 18 correlates with the prognosis of non-small cell lung cancer.

BACKGROUND: CC chemokine ligand 18 (CCL18) is a chemotactic cytokine involved in the pathogenesis and progression of various cancers. Our previous research showed that the expression of CCL18 is obviously higher in non-small cell lung cancer (NSCLC) than in the adjacent normal tissues, suggesting its role in NSCLC. METHODS: We further examined the serum level of CCL18 in 80 NSCLC patients with enzyme-linked immunosorbent assay and simultaneously analyzed the survival curve of these patients by the Kaplan-Meier method, and then utilized a log-rank test to evaluate the correlation of CCL18 expression with the malignant progression of NSCLC. RESULTS: Our results showed that the median serum concentration of CCL18 was significantly elevated to 436.11 ng/mL in NSCLC patients compared to 41.97 ng/ml in healthy people (P<0.01), which was also positively related to the expression of lung cancer biomarkers carcinoma-embryonic antigen and cytokeratin fragment antigen 21-1. Moreover, correlation analysis showed that an increased level of serum CCL18 was associated with a worse survival time in NSCLC patients. CONCLUSION: Our findings suggest that the serum CCL18 level of NSCLC patients was negatively correlated with the prognosis, thus suggesting that CCL18 may serve as a potential circulating biomarker for NSCLC diagnosis.

Positive expression of chemokine (C-C Motif) ligand 18 and prognosis in cancer: A meta-analysis.

PURPOSE: Chemokine (C-C Motif) Ligand 18 (CCL18) is a chemotactic cytokine involved in the pathogenesis and progression of various cancers by activating downstream signaling pathways and affecting cellular behaviors. We conducted a meta-analysis to evaluate the CCL18 as a prognostic marker for cancer and determine the relationship between CCL18 and clinicopathological features of cancer. METHODS: We searched the PubMed, Cochrane, Embase, Web of Science and SinoMed databases for publications to investigate the association between CCL18 expression and survival outcome in cancer. Hazard ratios (HRs) and 95% confidence intervals (CI) of overall survival (OS) were pooled. Odds ratios (ORs) of clinicopathological features were computed. Meta-analysis was performed using STATA 12.0 software. RESULTS: Our meta-analysis identified a total of 17 studies including 2829 cases. Meta-analysis revealed that the expression of CCL18 in various cancer tissues was significantly higher than that in the normal group (OR=16.694, 95% CI=14.117-27.476, p<0.01, random effects). The abnormal expression of CCL18 was associated with lymph node metastasis (OR=4.409, 95% CI=2.129-9.128, p<0.01, random effects) and TNM stage (breast cancer subgroup: III+IV vs I+II OR=13.187, 95% CI=8.417-20.660, p<0.01; gastric cancer subgroup: III+IV vs I+II OR=0.034, 95% CI=0.008-0.137, p<0.01) but is was not related to gender (male vs. female: OR=0.88, 95% CI=0.667-1.162, p=0.368) and age (>60 vs. ≤60 years: OR=1.118, 95% CI=0.795-1.571, p-0.522). CCL18 overexpression was associated with poor overall prognosis of breast cancer (Hazard Ratio/HR=2.969, 95% CI=1.361- 6.478, p<0.01, random effects). CONCLUSIONS: CCL18 is highly expressed in cancer tissues and is closely related to tumor metastasis and prognosis, and its role in tumor development is worth of further study.

Suppression of Postprandial Blood Glucose Fluctuations by a Low-Carbohydrate, High-Protein, and High-Omega-3 Diet via Inhibition of Gluconeogenesis.

Hyperglycemia significantly contributes to the development and progression of metabolic diseases. Managing postprandial blood glucose fluctuations is of particular importance for patients with hyperglycemia, but safe and effective means of reducing blood glucose levels are still lacking. Five diets with varying macronutrient ratios and omega-3 fatty acid amounts were tested for their blood glucose-lowering effects in male C57BL/6J mice. The diets with potent blood glucose-lowering effects were further investigated for their underlying mechanisms and their beneficial effects on hyperglycemia models. Mice given the low-carbohydrate, high-protein, and high-omega-3 (LCHP+3) diet exhibited a rapid reduction of the blood glucose levels that remained consistently low, regardless of feeding. These effects were associated with reduced amino acid gluconeogenesis, due to the inhibition of hepatic alanine transaminase (ALT). Furthermore, the LCHP+3 intervention was effective in reducing the blood glucose levels in several disease conditions, including type 1 diabetes mellitus, hormone-induced hyperglycemia, and diet-induced metabolic syndrome. Our findings identify the LCHP+3 diet as a potent blood glucose-lowering diet that suppresses postprandial blood glucose fluctuations through the inhibition of gluconeogenesis and may have great clinical utility for the management of metabolic diseases with hyperglycemia.

Identification of a sustainable two-plant diet that effectively prevents age-related metabolic syndrome and extends lifespan in aged mice.

The current system of food production is linked to both the increasing prevalence of chronic disease and the deterioration of the environment, and thereby calls for novel ways of producing nutritious foods in a sustainable manner. In the "longevity village" of Bama, China, we have identified two plant foods, hemp seed and bitter vegetable (Sonchus oleraceus), that are commonly consumed by its residents and grow abundantly in unfarmed land without fertilizers or pesticides. Here, we show that a diet composed of these two foods (the "HB diet") provides a sufficient variety of nutrients and confers significant health benefits. Aged mice allowed ad libitum access to the HB diet not only had longer life spans and improved cognitive function but were also protected against age-related metabolic syndrome, fatty liver, gut dysbiosis and chronic inflammation compared to aged mice fed a control Western diet. Furthermore, longevity-related genes (including 5'adenosine monophosphate-activated protein kinase, sirtuin 1, nuclear respiratory factor 1 and forkhead box O3) were significantly up-regulated, while aging-related genes (including mammalian target of rapamycin and nuclear factor kappa B) were down-regulated. These results demonstrate that the HB diet is capable of promoting health and longevity, and present a sustainable source of healthy foods that can help control the prevalence of chronic diseases and reduce agricultural impact on the environment.

Entecavir Combined With Adefovir Ameliorates Patients With Chronic Hepatitis B Who Fail to Respond to Nucleotide (Acid) Analog Monotherapy.

The aim of this study was to evaluate the efficacy and safety of entecavir (ETV) combined treatment with adefovir (ADV) on chronic hepatitic B (CHB) patients who failed to respond to nucleotide (acid) analog (NA) treatment. On this basis, the possible factors in the combined treatment of these patients will be analyzed. The safety, biochemical index, and the possible factors that might affect the ETV and ADV combined treatment at different points in time were retrospectively analyzed. The biochemical index included the following: virological response, hepatitis B virus (HBV) DNA decline, primary nonresponse, biochemical response, and the hepatitis B virus E antigen/hepatitis B virus E antibody seroconversion rate. There were 94 CHB patients and compensated liver cirrhosis patients who received ETV plus ADV treatment for over 12 weeks after failure of treatment with NAs. The authors have also investigated 76 CHB patients (80.9%) and 18 hepatitis B cirrhosis patients (19.1%) in this study. The HBV DNA baseline was 4.4 ± 1.4 log10 IU/mL, and the positive rate of HBeAg before salvage treatment was 78.7% (74/94). The sample sizes were 94, 78, 42, 10, 6, and 1 for follow-up of 24, 48, 96, 144, 192, and 240 weeks, respectively. The virological responses (HBV DNA < 2 log10 IU/mL) and biochemical responses were 52.1%, 74.3%, and 90.4% and 63.1%, 61.6%, and 81.1%, respectively, at 24, 48, and 96 weeks, which showed significant differences (P < 0.001 and P < 0.005, respectively). The HBV DNA decline was presented as mean ± SEM, which were 1.53 ± 1.23, 1.75 ± 1.37, 2.07 ± 1.54, and 2.39 ± 1.77 log10 IU/mL at 12, 24, 48, and 96 weeks, respectively. They showed significant differences compared with the baseline (χ = 8.084, P < 0.05). The rate of primary nonresponse was 30.9% (29/94), and the primary treatment failure rates were 26.6% (25/94), 24.4% (19/78), and 4.8% (2/42) at 24, 48, and 96 weeks, respectively. They all have statistical difference (P = 0.011 < 0.05). There were 23 patients who experienced virological breakthrough after the HBV DNA levels were undetectable, whereas after follow-up for 12-24 weeks, the HBV DNA levels were back to undetectable again. ETV plus ADV treatment is an efficient and safe treatment for CHB and compensated liver cirrhosis patients who experienced NA treatment failure. The high quantity of baseline HBV DNA level is a risk factor for poor efficacy of salvage treatment.

Meta-analysis of transcatheter arterial chemoembolization plus radiofrequency ablation versus transcatheter arterial chemoembolization alone for hepatocellular carcinoma.

This meta-analysis was conducted to compare transcatheter arterial chemoembolization (TACE) plus radiofrequency ablation (RFA) with TACE alone for hepatocellular carcinoma. We searched MEDLINE, EMBASE and CENTRAL for all relative randomized controlled trials (RCTs) and retrospective studies until October 31 2016. Tumor response, recurrence-free survival, overall survival and postoperative complications were the major evaluation indices. Review Manager (version 5.3) was used to analyze the data. Dichotomous data was calculated by odds ratio (OR) with 95% confidence intervals (CI). There were 1 RCT and 10 retrospective studies with 928 patients in this meta-analysis: 412 patients with TACE plus RFA and 516 patients with TACE alone. Compared with TACE alone group, TACE plus RFA group attained higher tumor response rates (OR = 6.08, 95% CI = 4.00 to 9.26, P < 0.00001), achieved longer recurrence-free survival rates (ORRFS = 3.78, 95% CI: 2.38 to 6.02, P < 0.00001) and overall survival rates (OR1-year = 3.92, 95% CI = 2.41-6.39, P < 0.00001; OR3-year = 2.56; 95% CI = 1.81-3.60; P < 0.00001; OR5-year = 2.78; 95% CI = 1.77-4.38; P < 0.0001). Serious postoperative complications were not observed, although complications were higher in TACE plus RFA group than that in TACE alone group (OR = 2.74, 95% CI = 1.07 to 7.07, P = 0.04). In conclusion, the use of TACE plus RFA for intermediate stage hepatocellular carcinoma can attain higher tumor response rates and improve survival rates than TACE alone.

Protection against fine particle-induced pulmonary and systemic inflammation by omega-3 polyunsaturated fatty acids.

BACKGROUND: Exposure to fine particulate matter, such as through air pollution, has been linked to the increased incidence of chronic diseases. However, few measures have been taken to reduce the health risks associated with fine particle exposure. The identification of safe and effective methods to protect against fine particle exposure-related damage is urgently needed. METHODS: We used synthetic, non-toxic, fluorescent fine particles to investigate the physical distribution of inhaled fine particles and their effects on pulmonary and systemic inflammation in mice. Tissue levels of omega-3 fatty acids were elevated via dietary supplementation or the fat-1 transgenic mouse model. Markers of pulmonary and systemic inflammation were assessed. RESULTS: We discovered that fine particulate matter not only accumulates in the lungs but can also penetrate the pulmonary barrier and travel into other organs, including the brain, liver, spleen, kidney, and testis. These particles induced both pulmonary and systemic inflammation and increased oxidative stress. We also show that elevating tissue levels of omega-3 fatty acids was effective in reducing fine particle-induced inflammation, whether as a preventive method (prior to exposure) or as an intervention (after exposure). CONCLUSIONS: These results advance our understanding of how fine particles contribute to disease development and suggest that increasing tissue omega-3 levels may be a promising nutritional means for reducing the risk of diseases induced by particle exposure. GENERAL SIGNIFICANCE: Our findings demonstrate that elevating tissue omega-3 levels can prevent and treat fine particle-induced health problems and thereby present an immediate, practical solution for reducing the disease burden of air pollution.

Possible Source Populations of the White-backed Planthopper in the Greater Mekong Subregion Revealed by Mitochondrial DNA Analysis.

The white-backed planthopper, Sogatella furcifera (Horváth) (Hemiptera: Delphacidae), is a serious pest of rice in Asia. However, little is known regarding the migration of this pest insect from the Greater Mekong Subregion (GMS) including Cambodia, Laos, Myanmar (Burma), Thailand, and Vietnam, into China's Yunnan Province. To determine the migration patterns of S. furcifera in the GMS and putative secondary immigration inside China's Yunnan Province, we investigated the population genetic diversity, genetic structure, and gene flow of 42 S. furcifera populations across the six countries in the GMS by intensive sampling using mitochondrial genes. Our study revealed the potential emigration of S. furcifera from the GMS consists primarily of three major sources: 1) the S. furcifera from Laos and Vietnam migrate into south and southeast Yunnan, where they proceed to further migrate into northeast and central Yunnan; 2) the S. furcifera from Myanmar migrate into west Yunnan, and/or central Yunnan, and/or northeast Yunnan; 3) the S. furcifera from Cambodia migrate into southwest Yunnan, where the populations can migrate further into central Yunnan. The new data will not only be helpful in predicting population dynamics of the planthopper, but will also aid in regional control programs for this economically important pest insect.

A host-microbiome interaction mediates the opposing effects of omega-6 and omega-3 fatty acids on metabolic endotoxemia.

Metabolic endotoxemia, commonly derived from gut dysbiosis, is a primary cause of chronic low grade inflammation that underlies many chronic diseases. Here we show that mice fed a diet high in omega-6 fatty acids exhibit higher levels of metabolic endotoxemia and systemic low-grade inflammation, while transgenic conversion of tissue omega-6 to omega-3 fatty acids dramatically reduces endotoxemic and inflammatory status. These opposing effects of tissue omega-6 and omega-3 fatty acids can be eliminated by antibiotic treatment and animal co-housing, suggesting the involvement of the gut microbiota. Analysis of gut microbiota and fecal transfer revealed that elevated tissue omega-3 fatty acids enhance intestinal production and secretion of intestinal alkaline phosphatase (IAP), which induces changes in the gut bacteria composition resulting in decreased lipopolysaccharide production and gut permeability, and ultimately, reduced metabolic endotoxemia and inflammation. Our findings uncover an interaction between host tissue fatty acid composition and gut microbiota as a novel mechanism for the anti-inflammatory effect of omega-3 fatty acids. Given the excess of omega-6 and deficiency of omega-3 in the modern Western diet, the differential effects of tissue omega-6 and omega-3 fatty acids on gut microbiota and metabolic endotoxemia provide insight into the etiology and management of today's health epidemics.