Stimulated Raman Scattering Microscopy Reveals Bioaccumulation of Small Microplastics in Protozoa from Natural Waters.

Microplastics (MPs) are pollutants of global concern, and bioaccumulation determines their biological effects. Although microorganisms form a large fraction of our ecosystem's biomass and are important in biogeochemical cycling, their accumulation of MPs has never been confirmed in natural waters because current tools for field biological samples can detect only MPs > 10 µm. Here, we show that stimulated Raman scattering microscopy (SRS) can image and quantify the bioaccumulation of small MPs (<10 µm) in protozoa. Our label-free method, which differentiates MPs by their SRS spectra, detects individual and mixtures of different MPs (e.g., polyethylene, polypropylene, polyvinyl chloride, polyethylene terephthalate, polystyrene, and poly(methyl methacrylate)) in protozoa. The ability of SRS to quantify cellular MP accumulation is similar to that of flow cytometry, a fluorescence-based method commonly used to determine cellular MP accumulation. Moreover, we discovered that protozoa in water samples from Yangtze River, Xianlin Wastewater Treatment Plant, Lake Taihu and the Pearl River Estuary accumulated MPs < 10 µm, but the proportion of MP-containing cells was low (∼2-5%). Our findings suggest that small MPs could potentially enter the food chain and transfer to organisms at higher trophic levels, posing environmental and health risks that deserve closer scrutiny.

Investigation of lethal thresholds of nanosecond pulsed electric field in rabbit VX2 hepatic tumors through finite element analysis and verification with a single-needle bipolar electrode: A prospective strategy employing three-dimensional comparisons.

Pulsed electric field has emerged as a promising modality for the solid tumor ablation with the advantage in treatment planning, however, the accurate prediction of the lesion margin requires the determination of the lethal electric field (E) thresholds. Herein we employ the highly repetitive nanosecond pulsed electric field (RnsPEF) to ablate the normal and VX2 tumor-bearing livers of rabbits. The ultrasound-guided surgery is operated using the conventional double- and newly devised single-needle bipolar electrodes. Finite element analysis is also introduced to simulate the E distribution in the practical treatments. Two- and three-dimensional investigations are performed on the image measurements and reconstructed calcification models on micro-CT, respectively. Specially, an algorithm considering the model surface, volume and shape is employed to compare the similarities between the simulative and experimental models. Blood vessel injury, temperature and synergistic efficacy with doxorubicin (DOX) are also investigated. According to the three-dimensional calculation, the overall E threshold is 4536.4 ± 618.2 V/cm and the single-needle bipolar electrode is verified to be effective in tissue ablation. Vessels are well preserved and the increment of temperature is limited. Synergy of RnsPEF and DOX shows increased apoptosis and improved long-term tumor survival. Our study presents a prospective strategy for the evaluation of the lethal E threshold, which can be considered to guide the future clinical treatment planning for RnsPEF.

Hemoglobin-to-Red Cell Distribution Width Ratio is Associated with All-Cause Mortality in Critically Ill Patients with Traumatic Brain Injury.

BACKGROUND: Hemoglobin-to-red cell distribution width ratio (HRR) has shown good prognostic value in various cancers. However, the relationship between HRR and outcomes in critically ill patients with traumatic brain injury (TBI) remains unclear. This study aimed to investigate the association between HRR and mortality among critically ill patients with TBI. METHODS: The Medical Information Mart for Intensive Care-IV (MIMIC-IV) database was utilized to conduct this retrospective cohort study. TBI patients were divided into four quartiles according to their HRR values. The primary outcome was 30-day mortality, whereas the secondary outcomes were 60-day and 120-day mortality. Univariable and multivariable Cox proportional risk models were performed to evaluate the hazard ratio (HR) and 95% confidence interval (CI) for the relationship between HRR and mortality. Receiver operating characteristic (ROC) curves were conducted to assess the prognostic value of HRR. RESULTS: For 30-day mortality, after adjustment for all potential covariates, the relationship remained significant with HRR treated as a continuous variable (HR, 95% CI: 0.87 [0.81, 0.92]; p < 0.001). In the fully adjusted model, the HR with 95% CI for the second, third, and fourth quartile groups were 0.67 (0.5, 0.9), 0.65 (0.46, 0.94), and 0.5 (0.32, 0.79), respectively, compared to the first quartile group. A similar relationship was also observed for 60-day mortality and 120-day mortality. HRR had a better predictive value than hemoglobin and red cell distribution width (RDW). CONCLUSIONS: A lower level of HRR is significantly associated with higher all-cause mortality among critically ill patients with TBI.

Neoadjuvant adebrelimab in locally advanced resectable esophageal squamous cell carcinoma: a phase 1b trial.

Overall survival (OS) benefits of neoadjuvant immunotherapy remain elusive in locally advanced esophageal squamous cell carcinomas (ESCC). Here, we reported the results of a phase 1b trial of neoadjuvant PD-L1 blockade with adebrelimab in resectable ESCC. Patients received two neoadjuvant doses of adebrelimab followed by surgery. The primary endpoints were safety and feasibility; secondary endpoints included pathologic complete response (pCR) and OS. Our data showed the primary endpoints of safety and feasibility had been met. Common treatment-related adverse events were anorexia (32%) and fatigue (16%), without grade 3 or more adverse events. Of the 30 patients enrolled in the trial, 25 underwent successful resection without surgery delay and 24% had major pathologic responses including a pCR rate of 8%. The 2-year OS was 92%. Responsive patients had an immune-enriched tumor microenvironment phenotype, whereas nonresponsive patients had greater infiltration of cancer-associated fibroblasts at baseline. Clonotypic dynamics of pre-existing intratumoral T cells was a hallmark of responsive patients. These findings provide a rational for neoadjuvant anti-PD-L1 monotherapy as a therapeutic strategy for patients with resectable ESCC. ClinicalTrials.gov identifier: NCT04215471 .

Direct Counting and Imaging Chain Lengths of Lipids by Stimulated Raman Scattering Microscopy.

Direct counting and mapping the chain lengths of fatty acids on a microscopic scale are of particular importance but remain an unsolvable challenge. Although the current hyperspectral stimulated Raman scattering (SRS) microscopy has gained exceptional capability in chemical imaging of the degree of desaturation, the complete lipid characterization, including the carbon chain length quantification, is awaiting a major breakthrough. Here, we pushed the spectral resolution limit of hyperspectral SRS microscopy to 5.4 cm-1 by employing a highly efficient spectral compressor, which achieved spectral narrowing of the fs laser without much energy loss. The SRS imaging with such high spectral resolution enabled us to differ eight types of saturated lipids with carbon chain lengths from C8:0 to C22:0 by interrogating their subtly red-shifting Raman bands of alkyl C-C gauche stretches between 1070 and 1110 cm-1. The SRS microscopy with superior spectral resolution will pave the way for comprehensive lipid characterization and contribute to uncovering the abnormal pathways of lipid metabolism in cancer.

Mechanisms of polyphenols on quality control of aquatic products in storage: A review.

Aquatic products are easily spoiled during storage due to oxidation, endogenous enzymes, and bacteria. At the same time, compared with synthetic antioxidants, based on the antibacterial and antioxidant mechanism of biological agents, the development of natural, nontoxic, low-temperature, better-effect green biological preservatives is more acceptable to consumers. The type and molecular structure of polyphenols affect their antioxidant and antibacterial effectiveness. This review will describe how they achieve their antioxidant and antibacterial effects. And the recent literature on the mechanism and application of polyphenols in the preservation of aquatic products was updated and summarized. The conclusion is that in aquatic products, polyphenols alleviate lipid oxidation, protein degradation and inhibit the growth and reproduction of microorganisms, so as to achieve the effect of storage quality control. And put forward suggestions on the application of the research results in aquatic products. We hope to provide theoretical support for better exploration of the application of polyphenols and aquatic product storage.

Hypoxia-induced RBBP7 promotes esophagus cancer progression by inducing CDK4 expression.

Hypoxia-induced epigenetic regulation calls for more effective therapeutic targets for esophageal cancer. We used GEPIA and UALCAN databases to screen survival-related and cancer stage-associated genes. Eca109 and KYSE450 esophageal cancer cell lines were cultured under normoxia, hypoxia, or CoCl-induced hypoxia conditions, which were further transfected with plasmids expressing RB binding protein 7 (RBBP7), hypoxia-inducible factor 1 (HIF1)-α, or RBBP7 shRNA. Colony formation and MTT assays were used to detect cell proliferation. Tumor sphere formation and stemness marker detection were applied to assess cell stemness. RT-PCR and western blot analysis were used to detect the relative mRNA level and protein expression, respectively. Luciferase assay was utilized to detect the direct interaction between HIF1α and RBBP7. Up-regulated RBBP7 was identified as one of the most prominent survival-related genes, which is negatively correlated with the overall survival (OS), disease recurrence-free survival (DFS), and tumor stages. Hypoxia-induced HIF1α up-regulates RBBP7 expression, which promotes esophagus cancer cell viability, proliferation, and stemness with increased cyclin-dependent kinase 4 (CDK4) expression. Luciferase reporter assay verified that HIF1α transcriptionally regulates the expression of RBBP7. We conclude that hypoxia induces high expression of RBBP7 which is at least partially mediated by HIF1α, up-regulates the expression of downstream CDK4, and thereby promotes tumor progression in esophageal cancer cells.

Long non-coding RNA DANCR accelerates colorectal cancer progression via regulating the miR-185-5p/HMGA2 axis.

Long non-coding RNAs (lncRNAs) are crucial players in tumour progression. Herein, this work was designated to decipher the clinical significance, function and molecular mechanism of a lncRNA, differentiation antagonizing non-coding RNA (DANCR) in colorectal cancer (CRC). Quantitative real-time polymerase chain reaction was adopted to examine DANCR, miR-185-5p and HMGA2 mRNA expressions in CRC tissues and cells. Both gain-of-function and loss-of-function cell models for DANCR were established, and then MTT, wound healing and Transwell, flow cytometry assays were carried out to detect the proliferation, migration, invasion, cell cycle and apoptosis of CRC cells. Dual-luciferase reporter gene assay and RIP assay were utilized to validate the targeting relationships between DANCR and miR-185-5p. Western blot was employed for detecting high mobility group A2 (HMGA2) expressions in CRC cells. In this study, we demonstrated that the expression of DANCR was elevated in CRC tissues and cell lines, and its high expression was significantly associated with increased TNM stage and positive lymph node metastasis. DANCR overexpression promoted CRC cell proliferation, migration, invasion and cell cycle progression, but inhibited apoptosis; while knocking down DANCR caused the opposite effects. DANCR was further identified as a molecular sponge for miR-185-5p, and DANCR could indirectly increase the expression of HMGA2 via repressing miR-185-5p. In conclusion, DANCR/miR-185-5p/HMGA2 axis participated in the progression of CRC.

Acupuncture for Quality of Life in Gastric Cancer Patients Undergoing Adjuvant Chemotherapy.

CONTEXT: Patients with gastric cancer experience health-related quality of life (HRQOL) decline during adjuvant chemotherapy following gastrectomy. OBJECTIVES: This pilot study aimed to evaluate the preliminary effect and feasibility of electro-acupuncture (EA) for HRQOL and symptom burden in these patients. METHODS: In this open-label, multicenter, parallel controlled trial, gastric cancer patients who planned to receive adjuvant chemotherapy were randomly assigned to receive high-dose EA (seven times each chemotherapy cycle for three cycles), low-dose EA (three times each chemotherapy cycle), or usual care only. The acupoints prescription consisted of bilateral ST36, PC6, SP4, and DU20, EX-HN3, and selected Back-shu points. Patients completed the Functional Assessment of Cancer Therapy-Gastric (FACT-Ga) weekly, and the Edmonton Symptom Assessment System (ESAS). The primary outcome was the difference among the groups on the gastric cancer subscale (GaCS) of the FACT-Ga. RESULTS: Of the 66 randomized patients, 58 were analyzed according to intention-to-treat principle, and 45 were in the per-protocol set (PPS). The average scores in PPS of GaCS were 52.12±9.71, 51.85±12.36, and 45.37±8.61 in high-dose EA, low-dose EA, and control groups, respectively. EA was significantly associated with improved average GaCS scores when compared with control group (51.98±10.91 vs. 45.37±8.61, P = 0.039). EA treatment also produced ESAS relief at the end of intervention (14.36 ± 12.28 vs. 23.91 ± 15.52, P = 0.027). Participants in EA groups had fewer grade ≥3 leukopenia (0% vs. 15.79%, P = 0.031) and neutropenia (2.56% vs. 26.31%, P = 0.012). CONCLUSION: EA showed promising effects in improving HRQOL, controlling symptom burden, and reducing toxicity during adjuvant chemotherapy in gastric cancer patients. Future adequately powered trials are feasible and needed to confirm the specific effect of EA.

Multi-Omics Analysis Reveals Disturbance of Nanosecond Pulsed Electric Field in the Serum Metabolic Spectrum and Gut Microbiota.

Nanosecond pulsed electric field (nsPEF) is a novel ablation technique that is based on high-intensity electric voltage to achieve tumour-killing effect in the target region, and increasingly considered for treating tumours of the liver, kidneys and other organs with rich blood supply. This study aims to observe effect of nsPFE treatment on serum metabolites and gut microbiota. The serum and faecal specimens of the pigs were collected pre- and post-treatment. The gut microbiota of pigs was sequenced by Illumina Miseq platform for analysing the diversity and alterations of gut microbiota. Liquid chromatography-mass spectrometry (LC-MS)-based metabonomic analysis and Pearson coefficient method were also used to construct the interaction system of different metabolites, metabolic pathways and flora. A total of 1,477 differential metabolites from the serum were identified by four cross-comparisons of different post-operative groups with the control group. In addition, an average of 636 OTUs per sample was detected. Correlation analysis also revealed the strong correlation between intestinal bacteria and differential metabolites. The nsPEF ablation of the liver results in a degree of liver damage that affects various metabolic pathways, mainly lipid metabolism, as well as gut microbiota. In conclusion, our study provided a good point for the safety and feasibility of applying nsPEF on liver through the integrated analysis of metabolomics and microbiomes, which is beneficial for the improvement of nsPEF in clinical use.

LncRNA MIAT Mediates ox-LDL-Induced Endothelial Cell Injury Via miR-206/RAB22A Axis.

BACKGROUND: Long non-coding RNA myocardial infarction associated transcript (MIAT) has exerted significant effects on atherosclerosis (AS). The biological roles of MIAT in endothelial cell dysfunction are not thoroughly elucidated. METHODS: The expression of MIAT, microRNA (miR)-206 and Ras-related protein Rab-22A (RAB22A) was detected by quantitative real-time polymerase chain reaction and western blot. The injury of human umbilical vein endothelial cells (HUVECs) was evaluated by testing cell viability, invasion, migration, apoptosis, epithelial-mesenchymal transition capacities and inflammatory response using cell counting kit-8, transwell, wound healing assays, flow cytometry, western blot and enzyme-linked immunosorbent assay, respectively. The binding interaction between miR-206 and MIAT or RAB22A was confirmed by dual-luciferase reporter and RNA immunoprecipitation assays. RESULTS: The expression of MIAT was up-regulated in ox-LDL-treated HUVECs, and knockdown of MIAT in ox-LDL-treated HUVECs remarkably promoted cell viability, invasion, migration, and epithelial-mesenchymal transition (EMT), as well as suppressed cell apoptosis and the levels of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α and endothelial nitric oxide synthase (eNOS). In a mechanical study, MIAT directly targeted miR-206, and miR-206 inhibition attenuated the protective effects of MIAT knockdown on ox-LDL-triggered HUVEC injury. Besides that, RAB22A was a target of miR-206, and RAB22A overexpression reversed the biological effects of miR-206 on ox-LDL-treated HUVECs. Additionally, we also proved MIAT could regulate RAB22A via miR-206 in HUVECs. CONCLUSION: MIAT knockdown impaired ox-LDL-induced HUVEC injury via regulating miR-206/RAB22A axis, suggesting the potential impacts of MIAT on AS occurrence, which revealed a potential therapeutic strategy for future clinic intervention in AS.

The effectiveness of EVOSKIN®Palm and sole moisturizing cream in treating capecitabine-associated hand-foot syndrome: a randomized double-blind clinical trial.

BACKGROUND: This study sought to test the effectiveness of EVOSKIN®Palm and sole moisturizing cream (PSMC) in preventing and treating hand-foot syndrome (HFS) during capecitabine chemotherapy. METHODS: Stage II/III colorectal cancer patients receiving capecitabine adjuvant chemotherapy were randomly allocated to receive either EVOSKINPSMC or physiological saline treatments for their hands and feet. Treatment was initiated along with adjuvant chemotherapy and continued till the end of chemotherapy. Participants' skin responses were evaluated every 3 weeks. RESULTS: During the study, 51 participants in the EVOSKIN PSMC group and 54 participants in the physiological saline group completed at least three cycles of capecitabine chemotherapy. The total incidence of HFS in the EVOSKIN PSMC group was lower than that in the physiological saline group (56.8% vs. 75.9%, P=0.006), as was the incidence of Grade 3/4 HFS (6.0% vs. 18.5%, P=0.011). The incidence of HFS became significant after 6weeks of chemotherapy. Further, the incidence of severe HFS was significant from as early as 3weeks after the commencement of chemotherapy despite the use of EVOSKIN PSMC to manage the condition. Notably, the incidence of Grade 1/2 HFS was not statistically significant between the two groups (26/51 vs. 32/54, 52.0% vs. 59.2%, P=0.194). CONCLUSIONS: The incidence of severe HFS among individuals using oral capecitabine can be reduced by the prophylactic treatment of EVOSKIN PSMC, this treatment is reasonable and acceptable for patients with capecitabine chemotherapy.

Establishment and Validation of Nomogram Model Integrated With Inflammation-Based Factors for the Prognosis of Advanced Non-Small Cell Lung Cancer.

OBJECTS: Inflammation is one of the hallmarks of cancer. Tumor-associated inflammatory response plays a crucial role in enhancing tumorigenesis. This study aimed to establish an effective predictive nomogram based on inflammation factors in patients with advanced non-small cell lung cancer (NSCLC). METHODS: We retrospectively evaluated 887 patients with advanced NSCLC between November 2004 and December 2015 and randomly divided them into primary (n = 520) and validation cohorts (n = 367). Cox regression analysis was used to identify prognostic factors for building the nomogram. The predictive accuracy and discriminative ability of the nomogram were determined using a concordance index (C-index), calibration plot, and decision curve analysis and were compared to the TNM staging system. RESULTS: The nomogram was established using independent risk factors (P < 0.05): age, TNM stage, C reaction protein-to-albumin ratio (CAR), and neutrophils (NEU). The C-index of the model for predicting OS had a superior discrimination power compared to that of the TNM staging system both in the primary [0.711 (95% CI: 0.675-0.747) vs 0.531 (95% CI: 0.488-0.574), P < 0.01] and validation cohorts [0.703, 95% CI: 0.671 -0.735 vs 0.582, 95% CI: 0.545-0.619, P < 0.01]. Decision curves also demonstrated that the nomogram had higher overall net benefits than that of the TNM staging system. Subgroup analyses revealed that the nomogram was a favorable prognostic parameter in advanced NSCLC (P < 0.05). The results were internally validated using the validation cohorts. CONCLUSIONS: The proposed nomogram with inflammatory factors resulted in an accurate prognostic prediction in patients with advanced NSCLC.

Combination of Plasma MIF and VCA-IgA Improves the Diagnostic Specificity for Patients With Nasopharyngeal Carcinoma.

INTRODUCTION: The purpose of this study is to evaluate the diagnostic value of macrophage migration inhibitory factor in patients with nasopharyngeal carcinoma. MATERIALS AND METHODS: The expression levels of macrophage migration inhibitory factor in nasopharyngeal carcinoma cell lines, tumor tissues, and plasma were measured by real-time polymerase chain reaction, Western blotting, enzyme-linked immunosorbent assay, and immunohistochemistry. Plasma Epstein-Barr virus viral capsid antigen was determined by immunoenzymatic techniques. RESULTS: Both the messenger RNA and protein expression levels of macrophage migration inhibitory factor were upregulated in nasopharyngeal carcinoma cell lines and nasopharyngeal carcinoma tissues. Macrophage migration inhibitory factor in plasma was significantly elevated in patients with nasopharyngeal carcinoma compared to Epstein-Barr virus viral capsid antigen-negative and Epstein-Barr virus viral capsid antigen-positive healthy donors. The combination of macrophage migration inhibitory factor and Epstein-Barr virus viral capsid antigen was better for diagnosing nasopharyngeal carcinoma (area under receiver operating characteristic curve = 0.925, 95% CI: 0.898-0.951) than macrophage migration inhibitory factor (area under receiver operating characteristic curve = 0.778, 95% CI: 0.732-0.824) and Epstein-Barr virus viral capsid antigen. Combining macrophage migration inhibitory factor and Epstein-Barr virus viral capsid antigen had higher specificity (82.40% vs 69.96%) and higher positive predictive value (79.17% vs 67.44%) without an obvious reduction in sensitivity (95.25%) compared to Epstein-Barr virus viral capsid antigen alone. Macrophage migration inhibitory factor was highly expressed in nasopharyngeal carcinoma cell lines, whereas it was not associated with Epstein-Barr virus infection. The level of macrophage migration inhibitory factor in plasma was not related to the titer of Epstein-Barr virus viral capsid antigen. CONCLUSION: The combination of macrophage migration inhibitory factor and Epstein-Barr virus viral capsid antigen increases the specificity and positive predictive value of detecting nasopharyngeal carcinoma and improves the diagnostic accuracy of nasopharyngeal carcinoma in high-risk individuals.

Interleukin-22 enhances chemoresistance of lung adenocarcinoma cells to paclitaxel.

The chemoresistance of tumors is the main barrier to cancer treatment. Interleukin-22 (IL-22) plays an important role in the chemoresistance of multi-cancers; however, the roles of IL-22 in the paclitaxel resistance of lung adenocarcinoma cells remain to be investigated. The present study aims to investigate the potential mechanisms of IL-22 enhancing the chemoresistance of lung adenocarcinoma cells to paclitaxel. We cultured A549, H358, and A549/PTX cell lines. qRT-PCR and western blot assays were performed to examine the mRNA and/or protein levels of IL-22 in A549, A549/PTX, H358, and H358/PTX. Moreover, cells were transfected with IL-22 siRNA1, IL-22 siRNA2, and siRNA NC, and treated with paclitaxel, and the proliferation rate of lung adenocarcinoma cells was evaluated by MTT assay. Flow cytometry was conducted to determine the apoptosis rate of lung adenocarcinoma cells. The results showed that the expression of IL-22 in lung adenocarcinoma tissues was higher than that in normal tissues, and the expression of IL-22 was higher in A549/PTX and H358/PTX compared with A549 and H358 cells. Meanwhile, the expression of IL-22 was strongly correlated with smoking history and TMN stage, as well. Furthermore, IL-22 siRNA inhibited the proliferation and promoted the apoptosis of A549/PTX and H358/PTX cells, and IL-22 siRNA also suppressed the expression levels of AKT and Bcl-2 and increased the expression levels of Bax and cleaved caspase 3. To sum up, IL-22 may mediate the chemosensitivity of lung adenocarcinoma cells to paclitaxel through inhibiting the AKT signaling pathways.

Systemic inflammatory response predicts poor prognoses in Barcelona Clinic Liver Cancer stage B/C hepatocellular carcinoma with transarterial chemoembolization: a prospective study.

BACKGROUND: Chronic inflammation has been demonstrated to be an important factor in the initiation, promotion, and progression of hepatocellular carcinoma (HCC). The aim of this study was to investigate the prognostic values of systemic inflammation markers in Barcelona Clinic Liver Cancer (BCLC) stage B/C HCC. METHODS: A prospective non-randomized study was performed from June 2016 to May 2017; 51 of 123 BCLC stage B/C HCC patients were enrolled and received transarterial chemoembolization (TACE). Clinical and laboratory data were recorded. Serum IL-6, IL-10, C-reactive protein (CRP), and blood-neutrophil-to-lymphocyte ratio (NLR) levels were analyzed during the perioperative period. Patient prognosis was investigated. Twenty-eight stage A cases and 10 stage B/C patients who received resection were also collected as controls. RESULTS: Compared to the stage A group, the BCLC stage B/C HCC patients had significantly higher serum IL-6, CRP, and blood NLR levels. Serum IL-6, IL-10, CRP, and blood NLR levels increased significantly 3 days after treatment (TACE/resection) and returned to baseline levels after 30 days. By univariate analyses, tumor size, high pretreatment serum IL-6, CRP, and blood NLR levels predicted worse progression-free survival (PFS) after TACE (log-rank test P<0.001, P=0.007, P=0.001, respectively). Multivariate analysis revealed that both high serum IL-6 (P=0.018) and CRP (P=0.042) were independent predictors of worse PFS, meanwhile blood NLR was the only inflammatory factor associated to overall survival (OS) (P=0.046). CONCLUSIONS: Serum IL-6, CRP, and blood NLR levels were significantly elevated in stage B/CHCC. Serum IL-6 and CRP were independent predictors of poor PFS while NLR independently predicted worse OS in BCLC stage B/C HCC.

Low circulating total adiponectin, especially its non-high-molecular weight fraction, represents a promising risk factor for colorectal cancer: a meta-analysis.

AIM: The principal goal of this meta-analysis is to test the hypothesis that circulating total adiponectin or certain fractions may represent a promising biological candidate in modulating the risk of colorectal cancer. METHODS: The processes of paper identification, paper selection and data extraction were accomplished independently by two authors. Effect-size estimates were expressed as weighted mean difference (WMD) and 95% confidence interval (95% CI). A total of 31 papers including 48 qualified studies (7,554 patients with colorectal cancer and 9,798 controls) were meta-analyzed. RESULTS: Pooling all studies found that circulating total adiponectin was significantly lower in patients with colorectal cancer than in controls (WMD: -0.76 µg/mL, 95% CI: -1.20 to -0.32, p=0.001), with significant heterogeneity (I2: 94.2%) and low publication bias (Egger's p=0.336). By adiponectin fractions, the difference in high-molecular weight (HMW) adiponectin was comparable between the two groups (WMD: -0.22 µg/mL, 95% CI: -0.70 to 0.25, p=0.350), while non-HMW adiponectin was significantly lower in patients with colorectal cancer than in controls (WMD: -0.27 µg/mL, 95% CI: -0.35 to -0.19, p<0.001), with marginal heterogeneity (I2: 52.3%). Subgroup analysis revealed that effect-size estimates were heterogeneous when grouping studies by cancer subtype, region, study design, matching status, gender and obesity. Further meta-regression analysis indicated that age and gender were significant potential sources of heterogeneity. The results showed the studied subgroups were not subject to publication bias (Egger's p<0.1). CONCLUSION: Our data collectively indicate that low circulating total adiponectin, especially its non-HMW fraction, represents a promising risk factor for colorectal cancer. Further studies are needed to explore underlying mechanisms.

Correction: Posttranscriptional regulation of Galectin-3 by miR-128 contributes to colorectal cancer progression.

[This corrects the article DOI: 10.18632/oncotarget.14839.].