Narrow band imaging might contribute to the diagnosis of laryngopharyngeal reflux.

PURPOSE: Laryngopharyngeal reflux (LPR) accounts for 4-10% of outpatient visits. The standard domestic LPR diagnostic tools are the reflux finding score (RFS) and reflux symptom index (RSI). Narrow band imaging (NBI) can identify previously unknown characteristic microvessel features. Our aim was to explore the role of NBI in LPR diagnosis. MATERIALS AND METHODS: We recruited 56 LPR outpatients and 41 symptom-negative controls. All individuals received RSI and RFS scores and underwent 24-hour multichannel intraluminal impedance-PH (MII-pH) monitoring and endoscopic NBI before and after treatment. The positivity rates in the study and control groups, before and after treatment, and using NBI and the conventional method were evaluated. RESULTS: Fifty-one LPR and six control patients had sparse light brownish dots or tufted light brownish dots in the postcricoid region. The RSI and RFS positivity rates were 31.3% and 87.1%, respectively. NBI is as effective as the RFS (P < 0.05), and has poor consistency with the RSI (P < 0.05). Fifty-three LPR patients underwent posttreatment laryngoscopy. The positivity rate decreased to 17.0% (P < 0.05). CONCLUSION: NBI has good value for LPR diagnosis.

Design, Synthesis and Bioactive Evaluation of Oxime Derivatives of Dehydrocholic Acid as Anti-Hepatitis B Virus Agents.

Oxime derivatives of dehydrocholic acid and its esters were designed for anti-hepatitis B virus (HBV) drugs according to principles of assembling active chemical fragments. Twelve compounds were synthesized from dehydrocholic acid by esterification and oxime formation, and their anti-hepatitis B virus (HBV) activities were evaluated with HepG 2.2.15 cells. Results showed that 5 compounds exhibited more effective inhibition of HBeAg than positive control, among them 2b-3 and 2b-1 showed significant anti-HBV activities on inhibiting secretion of HBeAg (IC50 (2b-3) = 49.39 ± 12.78 µM, SI (2b-3) = 11.03; IC50 (2b-1) = 96.64 ± 28.99 µM, SI (2b-1) = 10.35) compared to the Entecavir (IC50 = 161.24 µM, SI = 3.72). Molecular docking studies showed that most of these compounds interacted with protein residues of heparan sulfate proteoglycan (HSPG) in host hepatocyte and bile acid receptor.

Autophagy inhibition induces the repolarisation of tumour-associated macrophages and enhances chemosensitivity of laryngeal cancer cells to cisplatin in mice.

Tumour-associated macrophages (TAMs) are the key components in the tumour microenvironment. TAMs have two major subtypes, M1 and M2. M1 macrophages are tumour inhibitory, while M2 macrophages are tumour promotive. Repolarising TAMs from M2 to M1 is a promising strategy in cancer treatment. M1 and M2 macrophages were generated from murine bone marrow-derived macrophages (BMDMs). We found that chloroquine (CQ), an autophagy inhibitor, was able to repolarise M2 macrophages to the anti-tumour M1 phenotype. The repolarised macrophages demonstrated higher phagocytotic activity towards Hep-2 laryngeal tumour cells and re-sensitised Hep-2 cells to cisplatin (CDDP) treatment in vitro. While CQ did not demonstrate cytotoxicity to Hep-2 cells in vitro, CQ treatment reduced Hep-2 laryngeal tumour growth in vivo and improved CDDP treatment outcomes. It seems that CQ-induced M2-to-M1 macrophage repolarisation played an important role in tumour growth inhibition, and the CQ/CDDP combined therapy might have clinical potential in laryngeal cancer treatment.

MiR-199-3p-Dnmt3a-STAT3 signalling pathway in ovalbumin-induced allergic rhinitis.

NEW FINDINGS: What is the central question of this study? What is the mechanism of DNA methylation in allergic rhinitis? What is the main finding and its importance? A miR-199-3p-Dnmt3a-STAT3 signalling pathway is involved in ovalbumin-induced allergic rhinitis, and miR-199-3p antagomir can relieve the symptoms in the mouse model. ABSTRACT: Recent research has pointed out the involvement of epigenetic modifications in allergic rhinitis (AR), especially DNA methylation. However, the detailed mechanism has remained largely uncovered. We used ovalbumin (OVA) to induce AR in mouse, and behaviour scores were used to confirm its successful establishment. Histamine and other inflammatory factors were detected to further verify success of the model. Real-time PCR was employed to identify the overexpression of miR-199-3p and subsequent down-regulation of DNA methyltransferase 3a (Dnmt3a). Western blotting was utilized to detect Dnmt3a and signal transducer and activator of transcription 3 (STAT3) at the protein level. Bisulfite sequencing PCR was applied to reveal the methylation status of the Stat3 promoter region. A dual-reporter assay was used to confirm the direct targeting of miR-199-3p on the Dnmt3a mRNA and an antagomir specific to miR-199-3p was injected to rescue the symptoms of AR. The AR model was successfully established in mouse and confirmed by both behaviour and molecular markers. We also found lowered expression of Dnmt3a and consecutive hypomethylation of Stat3 promoter and elevated expression of STAT3, which then led to overexpression of IgE and other inflammatory factors. MicroRNAs that worked on the Dnmt3a 3'-untranslated region were predicted and then verified by dual-reporter assay. Finally injection of a miR-199-3p antagomir successfully attenuated the symptoms of AR. We propose that the miR-199-3p-Dnmt3a-STAT3 signalling pathway is involved in OVA-induced AR.

Design, Synthesis, and Bioactive Screen In Vitro of Cyclohexyl (E)-4-(Hydroxyimino)-4-Phenylbutanoates and Their Ethers for Anti-Hepatitis B Virus Agents.

A series of oxime Cyclohexyl (E)-4-(hydroxyimino)-4-phenylbutanoates and their ethers were designed, synthesized, and evaluated for anti-hepatitis B virus (HBV) activities with HepG 2.2.15 cell line in vitro. Most of these compounds possessed anti-HBV activities, and among them, compound 4B-2 showed significant inhibiting effects on the secretion of HBsAg (IC50 = 63.85 ± 6.26 µM, SI = 13.41) and HBeAg (IC50 = 49.39 ± 4.17 µM, SI = 17.34) comparing to lamivudine (3TC) in HBsAg (IC50 = 234.2 ± 17.17 µM, SI = 2.2) and HBeAg (IC50 = 249.9 ± 21.51 µM, SI = 2.07). Docking study of these compounds binding to a protein residue (PDB ID: 3OX8) from HLA-A2 that with the immunodominant HBcAg18-27 epitope (HLA-A2.1- restricted CTL epitope) active site was carried out by using molecular operation environment (MOE) software. Docking results showed that behaviors of these compounds binding to the active site in HLA-A protein residue partly coincided with their behaviors in vitro anti-HBV active screening.

Ferulic acid promotes survival and differentiation of neural stem cells to prevent gentamicin-induced neuronal hearing loss.

Neural stem cells (NSCs) have exhibited promising potential in therapies against neuronal hearing loss. Ferulic acid (FA) has been widely reported to enhance neurogenic differentiation of different stem cells. We investigated the role of FA in promoting NSC transplant therapy to prevent gentamicin-induced neuronal hearing loss. NSCs were isolated from mouse cochlear tissues to establish in vitro culture, which were then treated with FA. The survival and differentiation of NSCs were evaluated. Subsequently, neurite outgrowth and excitability of the in vitro neuronal network were assessed. Gentamicin was used to induce neuronal hearing loss in mice, in the presence and absence of FA, followed by assessments of auditory brainstem response (ABR) and distortion product optoacoustic emissions (DPOAE) amplitude. FA promoted survival, neurosphere formation and differentiation of NSCs, as well as neurite outgrowth and excitability of in vitro neuronal network. Furthermore, FA restored ABR threshold shifts and DPOAE in gentamicin-induced neuronal hearing loss mouse model in vivo. Our data, for the first time, support potential therapeutic efficacy of FA in promoting survival and differentiation of NSCs to prevent gentamicin-induced neuronal hearing loss.

The role of drug-induced sleep endoscopy: predicting and guiding upper airway surgery for adult OSA patients.

PURPOSE: Obstructive sleep apnea (OSA) is a common sleep disorder that can be corrected with upper airway surgery. Prior to surgery, drug-induced sleep endoscopy (DISE) is routinely used to evaluate obstruction sites and severity. Evidence suggests that the findings of DISE may relate to the final surgical outcome. Therefore, we evaluated the ability of drug-induced sleep endoscopy to predict the final effect of upper airway surgery and potentially to guide surgical treatment decision-making. METHODS: A retrospective analysis was conducted on 85 adult patients with OSA (50 men with mean apnea-hypopnea index [AHI] 30 ± 15 events/h) who underwent DISE followed by tonsillectomy, uvulopalatopharyngoplasty (UPPP), or a combination of the two. Surgery outcome was evaluated at follow-up by polysomnography. Success response to surgery was defined as a postoperative value of the AHI< 20 events/h and more than 50% postoperative reduction of AHI. RESULTS: Of the 85 patients evaluated, 48 (53%) were responders. DISE revealed significant differences between the two groups. Specifically, complete circumferential collapse at the velum and complete anterior-posterior collapse at the tongue base occurred at higher frequencies in nonresponders. In contrast, the presence of grade 3-4 tonsillar hypertrophy and anterior-posterior mild/partial collapse at the velum were positively associated with responders. CONCLUSIONS: Our results suggest that DISE may help predict the final outcome of tonsillectomy, UPPP, or a combination of the two in adult patients with OSA. The use of DISE shows potential to guide treatment decisions for individual patients with OSA.

Discovery of Oxime Ethers as Hepatitis B Virus (HBV) Inhibitors by Docking, Screening and In Vitro Investigation.

A series of oxime ethers with C6-C4 fragment was designed and virtually bioactively screened by docking with a target, then provided by a Friedel-Crafts reaction, esterification (or amidation), and oximation from p-substituted phenyl derivatives (Methylbenzene, Methoxybenzene, Chlorobenzene). Anti-hepatitis B virus (HBV) activities of all synthesized compounds were evaluated with HepG2.2.15 cells in vitro. Results showed that most of compounds exhibited low cytotoxicity on HepG2.2.15 cells and significant inhibition on the secretion of HBsAg and HBeAg. Among them, compound 5c-1 showed the most potent activity on inhibiting HBsAg secretion (IC50 = 39.93 µM, SI = 28.51). Results of the bioactive screening showed that stronger the compounds bound to target human leukocyte antigen A protein in docking, the more active they were in anti-HBV activities in vitro.

[Design, virtual screening, synthesis and anti-hepatitis B virus of oxime derivatives].

A series of new oxime and oxime ethers compounds were designed and virtually screened with target using the Molecular Operating Environment（MOE） software. Twelve unreported compounds including 4 oximes and 8 oxime ethers were synthesized with benzene, toluene, methoxybenzene and chlorobenzene as initial raw materials. Structures of compounds were elucidated by 1H NMR, 13C NMR and MS. The results of bioactive screening showed that a part of compounds displayed obviously anti-HBV activities. Inhibitory activities of compounds 4B-2 in secretion of HBsAg and HBeAg were IC50 HBsAg= 81.15 µmol·L-1, SIHBsAg = 9.20 and IC50 HBeAg = 90.66 µmol·L-1, SIHBeAg = 8.24, respectively. Preliminary structure-activity relationship study shows that methyl oxime ethers displayed better anti-HBV activities than the oximes.

The role of the mitochondrial ribosomal protein family in detecting hepatocellular carcinoma and predicting prognosis, immune features, and drug sensitivity.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumors, with a slow onset, rapid progression, and frequent recurrence. Previous research has implicated mitochondrial ribosomal genes in the development, metastasis, and prognosis of various cancers. However, further research is necessary to establish a link between mitochondrial ribosomal protein (MRP) family expression and HCC diagnosis, prognosis, ferroptosis-related gene (FRG) expression, m6A modification-related gene expression, tumor immunity, and drug sensitivity. METHODS: Bioinformatics resources were used to analyze data from patients with HCC retrieved from the TCGA, ICGC, and GTEx databases (GEPIA, UALCAN, Xiantao tool, cBioPortal, STRING, Cytoscape, TISIDB, and GSCALite). RESULTS: Among the 82 MRP family members, 14 MRP genes (MRPS21, MRPS23, MRPL9, DAP3, MRPL13, MRPL17, MRPL24, MRPL55, MRPL16, MRPL14, MRPS17, MRPL47, MRPL21, and MRPL15) were significantly upregulated differentially expressed genes (DEGs) in HCC tumor samples in comparison to normal samples. Receiver-operating characteristic curve analysis indicated that all 14 DEGs show good diagnostic performance. Furthermore, TCGA analysis revealed that the mRNA expression of 39 MRPs was associated with overall survival (OS) in HCC. HCC was divided into two molecular subtypes (C1 and C2) with distinct prognoses using clustering analysis. The clusters showed different FRG expression and m6A methylation profiles and immune features, and prognostic models showed that the model integrating 5 MRP genes (MRPS15, MRPL3, MRPL9, MRPL36, and MRPL37) and 2 FRGs (SLC1A5 and SLC5A11) attained a greater clinical net benefit than three other prognostic models. Finally, analysis of the CTRP and GDSC databases revealed several potential drugs that could target prognostic MRP genes. CONCLUSION: We identified 14 MRP genes as HCC diagnostic markers. We investigated FRG and m6A modification-related gene expression profiles and immune features in patients with HCC, and developed and validated a model incorporating MRP and FRG expression that accurately and reliably predicts HCC prognosis and may predict disease progression and treatment response.

Study on the Mechanism of the Combination of Methotrexate and Leflunomide in the Treatment of Rheumatoid Arthritis Based on Network Pharmacology, Molecular Docking, and in vitro Experimental Verification.

BACKGROUND: To date, disease-modifying antirheumatic drugs (DMARDs) are widely used as the primary first-line treatment option for patients with rheumatoid arthritis (RA), and the curative effect of methotrexate (MTX) and leflunomide (LEF; MTX + LEF) is greater than that of single-agent MTX therapy, but the synergistic mechanism of MTX + LEF is unclear. METHODS: First, we explored the mechanism of action of MTX + LEF in RA through network pharmacology and molecular docking. Venn diagram analysis revealed 97 overlapping gene targets of MTX + LEF-RA and STRING, along with Cytoscape plug-in MOCDE and cytoHubba; and GO enrichment analysis revealed that the functions of 97 synergistic targets were related to 123 molecular functions (MF), 63 cell components (CC), and 1,068 biological processes (BP). The Cytoscape plug-in ClueGO demonstrated that these targets were enriched in KEGG pathways of 52 terms, whereas 9 pivotal genes were mainly involved in the signaling pathways of estrogen, Ras, Rap1, PI3K-Akt, relaxin, TNF, AMPK, FoxO, prolactin, IL-17, and adherens junction. Finally, CETSA and DARTS validated the direct binding of MTX or LEF to the selected target proteins EGFR, PPARG, MMP9, and SRC in RAW264.7 cells. RESULTS: We identified 292 MTX targets and 247 LEF targets from 7 databases. Furthermore, 2,814 potential targets of RA were identified by merging 1,925 targets from 7 databases and 999 differentially expressed genes (DEGs) between normal controls and patients with RA extracted from 5 GEO databases. Nine pivotal genes, ESR1, ALB, CASP3, EGFR, HSP90AA1, SRC, MMP9, PPARG, and IGF1, were identified. Molecular docking verified that both MTX and LEF strongly bind to most of the 9 pivotal proteins except ESR1 and IGF1. CONCLUSION: These results contribute to our understanding of the enhancement mechanism of MTX combined with LEF and provide a targeted basis for the clinical treatment of RA.

Preemptive peritonsillar infiltration with lidocaine for relief of bipolar adult post-tonsillectomy pain: a randomized, double-blinded clinical study.

There are discordant results in the studies of the peritonsillar infiltration in adults undergoing the tonsillectomy. The study is to compare the effect of the preemptive peritonsillar infiltration with lidocaine in bipolar tonsillectomy in adult. 172 adult patients were randomly located into five groups before tonsillectomy: group 0: without the peritonsillar infiltration, group 1: for 3 ml normal saline with 1:200,000 epinephrine per tonsil, group 2: for 3 ml 1 %lidocaine with 1:200,000 epinephrine per tonsil, group 3: for 8 ml normal saline with 1:200,000 epinephrine per tonsil, group 4: for 8 ml lidocaine with 1:200,000 epinephrine per tonsil. The post-operative pain in the following 7 days was assessed by visual analog scale. Operation time and post-operative bleeding were also recorded. No significant differences were found between operative times, post-tonsillectomy hemorrhage between the five groups. The differences between pain scores of the group 0, group 1 and group 2 were not statistically significant (P > 0.05). The differences between pain scores of group 3, group 4 against group 0, group 1, group 2 were statistically significant (P < 0.05). We found the volume of peritonsillar infiltration might contribute to the relief of pain of the bipolar post-tonsillectomy.

Future trajectory of SARS-CoV-2: Constant spillover back and forth between humans and animals.

SARS-CoV-2, known as severe acute respiratory syndrome coronavirus 2, is causing a massive global public health dilemma. In particular, the outbreak of the Omicron variants of SARS-CoV-2 in several countries has aroused the great attention of the World Health Organization (WHO). As of February 1st, 2023, the WHO had counted 671,016,135 confirmed cases and 6,835,595 deaths worldwide. Despite effective vaccines and drug treatments, there is currently no way to completely and directly eliminate SARS-CoV-2. Moreover, frequent cases of SARS-CoV-2 infection in animals have also been reported. In this review, we suggest that SARS-CoV-2, as a zoonotic virus, may be frequently transmitted between animals and humans in the future, which provides a reference and warning for rational prevention and control of COVID-19.

A meta-analysis of short-term and long-term effects of indocyanine green fluorescence imaging in hepatectomy for liver cancer.

OBJECTIVES: This meta-analysis aimed to compare the short-term and long-term effects of indocyanine green fluorescence imaging in hepatectomy for liver cancer. METHODS: The databases PubMed, Embase, Scopus, Cochrane Library, Web of Science, ScienceDirect, and major scientific websites were screened up to January 2023. Randomized controlled trials and observational studies comparing fluorescence navigation-assisted and fluorescence-free navigation-assisted hepatectomy for liver cancer were included. Our meta-analysis comprises overall results and 2 subgroup analyses based on surgery type (laparoscopy and laparotomy). These estimates are presented as mean differences (MD) or odds ratio (OR) estimates with 95% CIs. RESULTS: We analyzed 16 studies that included 1260 patients with liver cancer. Our results showed that fluorescent navigation-assisted hepatectomy were significantly more shorter than fluorescence-free navigation-assisted hepatectomy in the following parameters: operative time [MD = -16.19; 95% CI: -32.27 to -0.11; p = 0.050], blood loss [MD = -107.90; 95% CI: -160.46 to -55.35; p < 0.001], blood transfusion [OR = 0.5; 95% CI: 0.35 to 0.72; p = 0.0002], hospital stay [MD = -1.60; 95% CI: -2.33 to -0.87; p < 0.001], and postoperative complications [OR = 0.59; 95% CI: 0.42 to 0.82; p = 0.002], The one-year disease-free survival rate [OR = 2.87; 95% CI: 1.64 to 5.02; p = 0.0002] was higher in the fluorescent navigation-assisted hepatectomy group. CONCLUSIONS: Indocyanine green fluorescence imaging has good clinical value and can improve the short-term and long-term results of hepatectomy for liver cancer.

The combination of insulin and linezolid ameliorates Staphylococcus aureus pneumonia in individuals with diabetes via the TLR2/MAPKs/NLRP3 pathway.

Diabetes mellitus (DM) complicated with Staphylococcus aureus (S. aureus) infection lacks effective treatment strategies. In this study, we found that insulin combined with linezolid has potential to deal with the thorny problem. In vitro, our drug sensitivity assay, bacterial growth curve and hemolytic tests showed that a combination of insulin and linezolid exerted good antibacterial and anti-α-hemolysin activity, CCK8 experiment, glucose content and glycogen content determination showed that the combination of insulin and linezolid increased murine macrophage survival rate and reduced the extracellular glucose level of high glucose-treated MH-S cells and intracellular glycogen level, and Western blot showed that the combination inhibited TLR2/MAPKs/NLRP3-related inflammatory pathways in MH-S cells. The results of in vivo experiments showed that the combination therapy stabilized glucose level, remained body weight, ameliorated lung injury including improving pulmonary edema and decreasing lung wet/dry weight ratio, reduced the CFUs and inflammation in the lung tissue in a mouse model of diabetes with S. aureus pneumonia, and inhibited the expression of TLR2, MAPKs and NLRP3 inflammatory pathway. Overall, the combination of insulin and linezolid as autolytic inhibitor exhibited the effects of significant antibacterial and improving glucose level in vitro and in vivo, and also has an anti-inflammation activity via the TLR2/MAPKs/NLRP3 pathway, this paves the way for new treatments for diabetes mellitus complicated with S. aureus infection.

Acute mesenteric ischemia secondary to oral contraceptive-induced portomesenteric and splenic vein thrombosis: A case report.

BACKGROUND: Mesenteric ischemia represents an uncommon complication of splanchnic vein thrombosis, and it is less infrequently seen in young women using oral contraceptives. Diagnosis is often delayed in the emergency room; thus, surgical intervention may be inevitable and the absence of thrombus regression or collateral circulation may lead to further postoperative ischemia and a fatal outcome. CASE SUMMARY: We report a 28-year-old female patient on oral contraceptives who presented with acute abdominal pain. Her physical examination findings were not consistent with her symptoms of severe pain and abdominal distention. These findings and her abnormal blood tests raised suspicion of acute mesenteric ischemia (AMI) induced by splanchnic vein thrombosis. Contrast-enhanced abdominal computed tomography revealed ischemia of the small intestine with portomesenteric and splenic vein thrombosis (PMSVT). We treated the case promptly by anticoagulation after diagnosis. We then performed delayed segmental bowel resection after thrombus regression and established collateral circulation guided by collaboration with a multidisciplinary team. The patient had an uneventful postoperative course and was discharged 14 d after surgery and took rivaroxaban orally for 6 mo. In subsequent follow-up to date, the patient has not complained of any other discomfort. CONCLUSION: AMI induced by PMSVT should be considered in young women who are taking oral contraceptives and have acute abdominal pain. Prompt anticoagulation followed by surgery is an effective treatment strategy.

The combination of cloxacillin, thioridazine and tetracycline protects mice against Staphylococcus aureus peritonitis by inhibiting α-Hemolysin-induced MAPK/NF-κB/NLRP3 activation.

Staphylococcus aureus (S. aureus) infection is difficult to fight, previous experimental reports have demonstrated thioridazine (TZ) and tetracycline (TC) is an inhibitor of S. aureus efflux pump NorA and autolysin Atl, respectively, here, by means of molecular docking and molecular dynamics simulation, we observed that thioridazine (TZ) and tetracycline (TC) blocked the binding of substrates to NorA and Atl, respectively, and reduced their activities, and our antibacterial susceptibility test and three-dimensional checkerboard method showed that the three-drug combination of antibiotic cloxacillin (CXN), TZ and TC had a synergistic anti-Staphylococcal activity in vitro, and α-Hemolysin tests and scanning electron microscopy showed that the three-drug combination and the subinhibitory concentration of the combination significantly inhibited the secretion of α-hemolysin relative to the number of membrane-derived vesicles produced by S. aureus. Whereas Western blot and pharmacological inhibition assays showed that the three-drug combination significantly inhibited the expression of MAPK/NF-κB/NLRP3 proteins in macrophages induced with S. aureus α-hemolysin. In vivo, the drug combination significantly reduced bacterial colony-forming unit counts in the viscera of a mouse peritonitis model of S. aureus infection, therapy reduced the primary inflammatory pathology and the bacteria-stimulated release of cytokines such as IL-1ß and TNF-α, and inhibited the expression of MAPK/NF-κB/NLRP3 proteins in peritoneal macrophages. Thus, the combination of efflux pump inhibitor, autolysis inhibitor and antibiotic, is a novel anti-Staphylococcal and anti-inflammatory strategy who owning good antibacterial activity and significant inhibiting staphylococcal α-hemolysin and inflammation.

Poly (I: C) inhibits reticuloendothelial virus replication in chicken macrophage-like cells through the activation of toll-like receptor-3 signaling.

Reticuloendothelial virus (REV) is widely found in many domestic poultry areas and results in severe immunosuppression of infected chickens. This increases the susceptibility to other pathogens, which causes economic losses to the poultry industry. The aim of our study was to determine whether polyinosinic-polycytidylic acid [Poly (I: C)] treatment could inhibit REV replication in chicken macrophage-like cell line, HD11. We found that Poly (I: C) treatment could markedly inhibit REV replication in HD11 from 24 to 48 h post infection (hpi). Additionally, Poly (I: C) treatment could switch HD11 from an inactive type into M1-like polarization from 24 to 48 hpi. Furthermore, Poly (I: C) treatment promoted interferon-ß secretion from HD11 post REV infection. Moreover, Toll-like receptor-3 (TLR-3) mRNA and protein levels in HD11 treated with Poly (I: C) were markedly increased compared to those of HD11 not treated with Poly (I: C). The above results suggested that Poly (I: C) treatment switches HD11 into M1-like polarization to secret more interferon-ß and activate TLR-3 signaling, which contributes to block REV replication. Our findings provide a theoretical reference for further studying the underlying pathogenic mechanism of REV and Poly (I: C) as a potential therapeutic intervention against REV infection.

The prognostic value of the C-reactive protein to albumin ratio in cancer: An updated meta-analysis.

BACKGROUND: Previous studies have demonstrated that the C-reactive protein to albumin ratio (CAR) is correlated with the clinical outcomes of solid tumors. However, the available data have not been systematically evaluated. The objective of the present meta-analysis was to explore the prognostic value of the CAR in solid tumors. METHODS: Eligible studies were identified from the PubMed, EMBASE and Web of Science electronic databases. The clinical characteristics, disease -free survival (DFS) /progression-free survival (PFS) and overall survival (OS) were extracted from the eligible studies. The pooled hazard ratios (HRs) and 95% confidence intervals were calculated with STATA 12.0 software. We also performed subgroup, meta-regression and sensitivity analyses. RESULTS: In total, twenty-seven eligible studies including 10556 patients were enrolled in the present meta-analysis. The pooled HRs with 95% confidence intervals showed that the CAR was significantly associated with poor OS (HR = 1.95, 95% CI: 1.71-2.22) and DFS/PFS (HR = 1.82, 95% CI: 1.61-2.07) in patients with solid tumors. Although publication bias was found in the studies with regard to OS, a further trim and fill analysis revealed that the adjusted HR was 1.82 (95% CI: 1.69-1.96), which was close to the original HR. Subgroup analysis confirmed the CAR as a strong prognostic marker in patients with solid tumors, regardless of the tumor type, detection time, cut-off value, sample size and area. CONCLUSION: Our meta-analysis indicated that a high CAR might be an unfavorable prognostic marker for OS and DFS/PFS in patients with solid tumors.

Bone Marrow Mesenchymal Stem Cells Promote the Stemness of Hypopharyngeal Cancer Cells.

A study was to investigate the regulation of bone marrow mesenchymal stem cells (BMSCs) on the stemness of hypopharyngeal cancer cells (FaDu cells). Green fluorescent protein-labeled FaDu cells were cocultured with BMSCs and then were isolated. In vitro experiments, including cell cycle and apoptosis analyses and clonogenic and sphere formation assays, were conducted using the cocultured FaDu cells to determine the stemness of FaDu cells. The tumor formation assay was performed through subcutaneous injection of FaDu cells into nude mice to determine the tumorigenic ability of FaDu cells after coculture. Immunohistochemical analysis of CD44 and ALDH1 was performed on the tumor tissue. After coculturing with human BMSCs, the ratio of FaDu cells at G2 phase was increased, while the ratios at S and G1 phases were decreased. In addition, coculture reduced apoptosis, but increased the clonogenic ability and sphere formation efficiency of FaDu cells. Finally, coculturing FaDu cells induced more robust and faster tumor formation as well as increased expression levels of CD44 and ALDH1 in tumor tissue. BMSCs promote the stemness of hypopharyngeal cancer cells.