Investigating oral microbiome profiles in patients with cleft lip and palate compared with the healthy control.

BACKGROUND: Patients with cleft lip and palate (CLP) have an oronasal communication differed from the closed state in healthy individuals, leading to a unique oral microbiome. This study aimed to determine if variances in the oral microbiota persist among CLP patients who have received treatments for the closure of these fistulas compared to the microbiota of healthy individuals. METHODS: Saliva samples were collected from a cohort comprising 28 CLP patients (CLP group) and 30 healthy controls (HC group). Utilizing 16S rRNA sequencing on the Illumina NovaSeq platform, we conducted a comprehensive analysis of the diversity and composition of the oral microbiota. RESULTS: The analysis of the microbiota in the saliva samples revealed a total of 23 microbial phyla, 38 classes, 111 orders, 184 families, 327 genera and 612 species. The alpha diversity with microbial abundance and evenness indicated the significant difference between the CLP and HC groups. Principal coordinate analysis (PCoA) and the ADONIS test further supported the presence of distinct microorganisms between the two groups. The CLP group displayed elevated abundances of Neisseria, Haemophilus, Porphyromonas, and Granulicatella, as indicated by LefSe analysis. Conversely, Rothia, Veillonella, and Pauljensenia exhibited significant reductions in abundance in the CLP group. The results of the PICRUSt analysis indicated significant differences in the relative abundance of 25 KEGG pathways within the CLP group. Through Spearman correlation analysis, strong associations between Rothia, Veillonella, and Pauljensenia and 25 functional pathways linked to CLP were identified. CONCLUSION: Findings of this study offer a thorough comprehension of the microbiome profiles of CLP patients after the restoration of oronasal structure and are anticipated to present innovative concepts for the treatment of CLP.

Porphyromonas gingivalis OMVs promoting endothelial dysfunction via the STING pathway in periodontitis.

OBJECTIVE: This study aimed to assess the effects of Porphyromonas gingivalis outer membrane vesicles (Pg-OMVs) in chronic periodontitis and explore the underlying mechanism involved. METHODS: In vitro, Pg-OMVs were incubated with Ea.hy926 (vessel endothelial cells, ECs) to evaluate their effects on endothelial functions and to investigate the underlying mechanism. The effects of endothelial dysfunction on MG63 osteoblast-like cells were verified using an indirect co-culture method. For in vivo studies, micro-CT was conducted to identify alveolar bone mass. Immunofluorescence staining was conducted to confirm the levels of stimulator of interferon genes (STING) in the blood vessel and the number of Runx2+ cells around the alveolar bone. RESULTS: Pg-OMVs were endocytosed by ECs, leading to endothelial dysfunction. The cGAS-STING-TBK1 pathway was activated in ECs, which subsequently inhibited MG63 migration and early osteogenesis differentiation. In vivo, Pg-OMVs promoted alveolar bone resorption, increased STING levels in the blood vessel, and decreased Runx2+ cells around the alveolar bone. CONCLUSIONS: Pg-OMVs caused endothelial dysfunction and activated the cGAS-STING-TBK1 signal cascade in ECs, thereby impairing ECs-mediated osteogenesis. Furthermore, Pg-OMVs aggregated alveolar bone loss and altered the blood vessel-mediated osteogenesis with elevated STING.

Phthalate exposure aggravates periodontitis by activating NFκB pathway.

BACKGROUND: Phthalates are widely used plasticizers, which were identified as risk factors in the development of many human diseases. However, the effects of phthalates in the periodontitis are unknown. We aimed to investigated the relationship of periodontitis and phthalate exposure as well as the underlying mechanisms. MATERIALS AND METHODS: Univariate and multivariate logistic regressions were employed to evaluate the association between phthalate metabolites and periodontitis. The generalized additive model and piecewise logistic regression were conducted to investigate the dose-response relationship. Cell and animal models were used to explore the role and mechanism of DEHP in the development of periodontitis. Transcriptome sequencing, bioinformatics analysis, western blot, immunofluorescence and mice model of periodontitis were also employed. RESULTS: MEHP (OR 1.14, 95% CI 1.05-1.24), MCPP (OR 1.08, 95% CI 1.00-1.17), MEHHP (OR 1.18, 95% CI 1.08-1.29), MEOHP (OR 1.18, 95% CI 1.07-1.29), MiBP (OR 1.15, 95% CI 1.04-1.28), and MECPP (OR 1.20, 95% CI 1.09-1.32) were independent risk factors. And MEHHP, the metabolite of DEHP, showed the relative most important effects on periodontitis with the highest weight (0.34) among all risk factors assessed. And the increase of inflammation and the activation of NFκB pathway in the periodontitis model mice and cells were observed. CONCLUSION: Exposure to multiple phthalates was positively associated with periodontitis in US adults between 30 and 80 years old. And DEHP aggravated inflammation in periodontitis by activating NFκB pathway.

Identification and verification of novel immune-related ferroptosis signature with excellent prognostic predictive and clinical guidance value in hepatocellular carcinoma.

Background: Immunity and ferroptosis often play a synergistic role in the progression and treatment of hepatocellular carcinoma (HCC). However, few studies have focused on identifying immune-related ferroptosis gene biomarkers. Methods: We performed weighted gene co-expression network analysis (WGCNA) and random forest to identify prognostic differentially expressed immune-related genes (PR-DE-IRGs) highly related to HCC and characteristic prognostic differentially expressed ferroptosis-related genes (PR-DE-FRGs) respectively to run co-expression analysis for prognostic differentially expressed immune-related ferroptosis characteristic genes (PR-DE-IRFeCGs). Lasso regression finally identified 3 PR-DE-IRFeCGs for us to construct a prognostic predictive model. Differential expression and prognostic analysis based on shared data from multiple sources and experimental means were performed to further verify the 3 modeled genes' biological value in HCC. We ran various performance testing methods to test the model's performance and compare it with other similar signatures. Finally, we integrated composite factors to construct a comprehensive quantitative nomogram for accurate prognostic prediction and evaluated its performance. Results: 17 PR-DE-IRFeCGs were identified based on co-expression analysis between the screened 17 PR-DE-FRGs and 34 PR-DE-IRGs. Multi-source sequencing data, QRT-PCR, immunohistochemical staining and testing methods fully confirmed the upregulation and significant prognostic influence of the three PR-DE-IRFeCGs in HCC. The model performed well in the performance tests of multiple methods based on the 5 cohorts. Furthermore, our model outperformed other related models in various performance tests. The immunotherapy and chemotherapy guiding value of our signature and the comprehensive nomogram's excellent performance have also stood the test. Conclusion: We identified a novel PR-DE-IRFeCGs signature with excellent prognostic prediction and clinical guidance value in HCC.

Transcriptome and targeted metabolomic integrated analysis reveals mechanisms of B vitamin accumulation in Areca catechu nut development.

Areca catechu is well known as a medicinal plant that has high nutritional and medicinal benefits. However, the metabolism and regulatory mechanism of B vitamins during areca nut development remain largely unclear. In this study, we obtained the metabolite profiles of six B vitamins during different areca nut developmental stages by targeted metabolomics. Furthermore, we obtained a panoramic expression profile of genes related to the biosynthetic pathway of B vitamins in areca nuts at different developmental stages using RNA-seq. In total, 88 structural genes related to B vitamin biosynthesis were identified. Furthermore, the integrated analysis of B vitamin metabolism data and RNA-seq data showed the key transcription factors regulating thiamine and riboflavin accumulation in areca nuts, including AcbZIP21, AcMYB84, and AcARF32. These results lay the foundation for understanding metabolite accumulation and the molecular regulatory mechanisms of B vitamins in A. catechu nut.

Neutrophil-to-lymphocyte and hypopharyngeal cancer prognosis: System review and meta-analysis.

Several studies have reported the value of neutrophil-to-lymphocyte ratio (NLR) for the prognosis of hypopharyngeal cancer. However, contradictory findings have also been published. We aimed to clarify the effect of NLR on the prognosis of hypopharyngeal cancer through meta-analysis. Systematic search of PubMed and other database with study selection and data extraction. The combined hazard ratio (HR) and 95% confidence intervals (CI) were calculated using STATA, applying either a fixed-effects or random-effects model. Meta-regression, subgroup analysis, and sensitivity analysis were used to analyze sources of heterogeneity. Publication bias were also assessed. This meta-analysis included 2232 patients with hypopharyngeal cancer from seven studies. The combined HR (OS, HR = 1.80, 95CI%, 1.14-2.82; PFS, HR = 1.88, 95CI%, 1.26-2.79) suggested that high NLR was associated with poor overall survival (OS) and progression-free survival (PFS). Pretreatment NLR can be used as an effective serological indicator to assess the prognosis of patients with hypopharyngeal cancer.

Increased IL-1α expression in chronic rhinosinusitis with nasal polyps.

PURPOSE: To examine whether and how interleukin (IL)-1α is involved in chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: Nasal polyp (NP) and control tissues were collected from CRSwNP patients and control subjects. The expression of IL-1α and other proinflammatory cytokines (IL-1ß, IL-8 and IL-13, etc.), as well as neutrophil and eosinophil accumulation, were examined in sinonasal tissues using immunohistochemical (IHC), immunofluorescent (IF) staining, qPCR, and Luminex, respectively. Moreover, the regulation of IL-1α expression and its effects on other proinflammatory cytokines were evaluated in cultured nasal epithelial cells (NECs). RESULTS: The mRNA and protein levels of IL-1α were significantly higher in NP tissues compared to that in control tissues. IL-1α in polyp tissues was mainly located in epithelial cells and neutrophils. Polyps IL-1α level was significantly associated with IL-8, IL-1ß, IL-6, IL-4 and IL-13 production, as well as tissue neutrophil infiltration. Moreover, poly (I:C), lipopolysaccharides, Flagellin, R848 and cytokines (IL-4, IL-5, and IL-13) significantly increased the expression of IL-1α in cultured NECs in vitro, and recombinant IL-1α significantly promoted production of IL-8 and CXCL1 in cultured NECs. CONCLUSIONS: These findings provided the evidence that IL-1α were significantly increased in NP tissues, which may contribute to tissue neutrophilia in CRSwNP patients in China.

Prognostic value of the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in laryngeal cancer: What should we expect from a meta-analysis?

Background: Although many studies have shown the predictive value of the high neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) for various cancers, there are conflicting reports regarding their role in laryngeal cancer. This study aimed to evaluate the relationship between high NLR/PLR and laryngeal cancer prognosis with the help of meta-analysis. Methods: PubMed, Embase and other databases were used to search relevant studies. The pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated using either the random-effect-model or fixed-effect model. Sensitivity analyses and subgroups were used to explore potential sources of heterogeneity. Publication bias was also adopted. Result: 5716 patients from 20 studies were involved in this meta-analysis. Pooled observed survival (OS) (HR=1.70, 95%CI, 1.41-2.04, p<0.001), progression-free survival (PFS) (HR=1.81, 95%CI, 1.47-2.23, p<0.001), and disease-free survival (DFS) (HR=1.86, 95%CI, 1.45-2.38, p<0.001) showed the prediction of high NLR for poor prognosis. It also suggested that high PLR predicted poor OS (HR=1.89, 95%CI, 1.21-2.94, p<0.001). Conclusion: This study indicated that high NLR was associated with poor OS, PFS, and DFS in laryngeal cancer patients, and high PLR was related to poor OS. Both could be potential predictors of prognosis.

Serum and glucocorticoid-regulated kinase 1 regulates transforming growth factor ß1-connective tissue growth factor pathway in chronic rhinosinusitis.

PURPOSE: Serum/glucocorticoid-regulated kinase 1 (SGK1) has been identified as a crucial regulator in fibrotic disorders. Herein, we explored SGK1 role in tissue remodeling of chronic rhinosinusitis (CRS). METHODS: Lentivirus was employed to generate an SGK1-overexpressing human bronchial epithelial cell (16HBE) line. To screen SGK1 downstream genes, RNA sequencing was performed on SGK1-overexpressing and control cell lines. To determine protein and gene expression levels, immunohistochemistry, western blotting, and quantitative real-time polymerase chain reaction were employed. Correlation analysis was performed using mRNA expression levels of SGK1, transforming growth factor ß1 (TGF-ß1), and connective tissue growth factor (CTGF) derived from CRS mucosal tissue and GEO database. Gene set enrichment analysis was conducted using gene sets from Molecular Signatures Database. The severity of symptoms in CRS patients was assessed using the 22-Item Sinonasal Outcome Test. RESULTS: SGK1 overexpression significantly increased the expression of connective tissue growth factor (CTGF) in 16HBE cells (P < 0.01). Consistently, CTGF protein level was considerably greater in mucosal tissue of CRS without nasal polyps (CRSsNP) than in CRS with nasal polyps (CRSwNP) (P < 0.05) or in control subjects (P < 0.01). TGF-ß1 protein level was higher in mucosal tissue of CRSsNP patients than in CRSwNP patients (P < 0.001) or in the control group (P < 0.01). mRNA levels of SGK1 and CTGF (P < 0.05, r = 0.668; P = 0.001, r = 0.630), TGF-ß1 and CTGF (P < 0.05, r = 0.560; P < 0.05, r = 0.420), as well as SGK1 and TGF-ß1(P < 0.05, r = 0.612; P < 0.05, r = 0.524) were significantly correlated in CRS mucosal tissue and GSE36830 dataset, respectively. TGF-ß1-induced upregulated genes were significantly enriched in SGK1 overexpression group. In vitro assays, TGF-ß1 promoted SGK1 and CTGF expression in a concentration- and time-dependent manner. Administrating an SGK1 inhibitor, GSK650394, significantly inhibited TGF-ß1-induced CTGF expression in 16HBE and dispersed primary nasal polyp cells. CONCLUSIONS: TGF-ß1 stimulation significantly increases SGK1 and CTGF expression. By regulating TGF-ß1-CTGF pathway, SGK1 may participate in tissue remodeling in the pathological mechanism of CRS.

TGF-ß1 induces epithelial-to-mesenchymal transition in chronic rhinosinusitis with nasal polyps through microRNA-182.

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) in nasal epithelial cells is involved in tissue remodeling of chronic rhinosinusitis with nasal polyps (CRSwNP). Our study investigated the molecular mechanisms that microRNA-182 (miR-182) regulated EMT in eosinophilic (Eos) and non-eosinophilic (non-Eos) CRSwNP. OBJECTIVE: To investigate the mechanism by which miR-182 regulates EMT in human nasal epithelial cells (hNEPCs). METHODS: The expression of EMT markers (E-cadherin, N-cadherin and vimentin), transforming growth factor (TGF)-ß1, and miR-182 were determined by western blotting and reverse transcription-quantitative PCR (RT-qPCR). Fluorescence in situ hybridization (FISH) was used to detect the miR-182 localization. Additionally, EMT markers expression and cell morphology changes were checked upon treatment with TGF-ß1, or TGF-ß1 with miR-182 inhibitor, or miR-182 mimics, or miR-182 inhibitor alone in hNEPCs. RESULTS: In both Eos CRSwNP and non-Eos CRSwNP, the expression levels of E-cadherin were downregulated while the expression levels of N-cadherin, vimentin, TGF-ß1 and miR-182 were significantly upregulated compared with control nasal tissues. Additionally, more significant changes in these EMT markers were observed in the Eos-CRSwNP when compared with the non-Eos CRSwNP. Invitro hNEPCs model, TGF-ß1 upregulated miR-182 expression and promoted EMT in hNEPCs, indicated by changes in cell morphology and EMT markers expression. Furthermore, these upregulations were reversed by miR-182 inhibitor. CONCLUSIONS: This study showed that miR-182-induced EMT in response to TGF-ß1 might promote nasal polypogenesis in both Eos CRSwNP and non-Eos CRSwNP, thus providing potential targets for the future development of novel therapeutic approaches for the management of CRSwNP.

CRISPR-based RNA-binding protein mapping in live cells.

RNA-binding proteins (RBPs) are involved in all aspects of RNA metabolism, and RNA-RBP interactions are important for cell homeostasis and viral replication. The global RNA-binding proteome was recently reported; however, little is known about the proteins that bind to specific RNAs. In this study, we describe a novel CRISPR-based RNA interaction proteomics method in live cells. In brief, dCas13a with an HA tag was expressed in cells and bound to an RNA of interest with the help of gRNA. The RNA-protein complexes physically bound to dCas13a-HA were crosslinked using UV light and captured using anti-HA beads, after which the proteins were purified and identified using mass spectrometry. We optimized this system and subsequently applied it to U1 small nuclear RNA, which revealed 226 proteins.

Green Conversion of Saponins to Diosgenin in an Alcoholysis System Catalyzed by Solid Acid Derived from Phosphorus Tailings.

This work proposed to prepare solid acid from phosphorus tailings and successfully convert Dioscorea zingiberensis C.H. Wright (DZW) into diosgenin from the perspective of solid waste resource reuse and clean production. The results showed that SiO2-SO3H solid acid could catalyze the production of diosgenin from total saponins under solvothermal reaction conditions. In addition, the parameters of a single factor, such as the amount of SiO2-SO3H, solvent volume, reaction temperature, and reaction time, were optimized to confirm the optimal range of reaction conditions, and the optimal process conditions were determined by the response surface method. The yield of diosgenin was 2.45 ± 0.17% under the optimum conditions, and the yield of diosgenin was increased by 12.90% compared with the traditional acid hydrolysis process. Except the relatively higher catalytic activity, the alcoholysis approach for the production of diosgenin has no waste liquid to discharge. The products were analyzed by high-performance liquid chromatography-mass spectrometry, and the pathway to convert total saponins into diosgenin under SiO2-SO3H has been proposed. Moreover, the adopted catalyst can be prepared with very low cost from phosphorus tailings. Considering the obvious superiorities, the alcoholysis approach in this work could be a promising strategy for green production of diosgenin as well as a possible utilization pathway of phosphorus tailings.

Circ-ATP5H Induces Hepatitis B Virus Replication and Expression by Regulating miR-138-5p/TNFAIP3 Axis.

BACKGROUND: Circular RNAs (circRNAs) play an important regulatory role in various cancers, including hepatocellular carcinoma (HCC). This study aimed to investigate the function of hsa_circ_0006942 (circ-ATP5H) in hepatitis B virus (HBV)-associated HCC and its underlying mechanism. METHODS: The levels of circ-ATP5H, miR-138-5p and tumor necrosis factor alpha-induced protein 3 (TNFAIP3) were determined using quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot assay. The copies of HBV DNA were examined using qRT-PCR. The levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were detected via enzyme-linked immunosorbent assay (ELISA). Dual-luciferase reporter assay was used to analyze the interactions among circ-ATP5H, miR-138-5p and TNFAIP3. RESULTS: Circ-ATP5H and TNFAIP3 levels were increased, while miR-138-5p level was reduced in HBV-positive HCC tissues and cells. Knockdown of circ-ATP5H hindered HBV DNA replication and decreased HBsAg and HBeAg levels in HBV-infected cells. Circ-ATP5H silencing suppressed HBV replication and expression by regulating miR-138-5p. Moreover, miR-138-5p blocked HBV replication and expression via targeting TNFAIP3. Furthermore, circ-ATP5H up-regulated TNFAIP3 via absorbing miR-138-5p. CONCLUSION: Circ-ATP5H promoted HBV replication and expression through modulating miR-138-5p/TNFAIP3 axis, suggesting a new biomarker for HBV-related HCC treatment.

Intravenous parecoxib for early postoperative cognitive dysfunction in elderly patients: evidence from a meta-analysis.

BACKGROUND: Inflammation plays a key role in the etiology and pathology of postoperative cognitive dysfunction (POCD). Cyclooxygenase (COX)-2 inhibitor parecoxib is used for the treatment of acute pain due to its potent anti-inflammatory and analgesic effects. Herein, we evaluated the efficacy and safety of parecoxib on early POCD in geriatric patients. OBJECTIVE: This study was performed to evaluate the efficacy and safety of parecoxib for early postoperative cognitive dysfunction (POCD) in elderly patients. METHODS: Comprehensive literature search based on six electronic databases was applied to retrieve all related randomized controlled trials (RCTs). Two independent reviewers screened each article for eligibility according to the predetermined inclusion criteria. The Cochrane's Tool was applied to evaluate the methodological quality of included studies. RevMan 5.3 was used to conduct meta-analysis. RESULTS: Eight RCTs comprising a total of 1106 subjects prepared for orthopedic surgical operation were selected. All the identified RCTs were conducted in China. The methodological qualities of included studies were judged to be medium to high. The integrated data showed that perioperative intravenous parecoxib could remarkably reduce the incidence of POCD with improved Mini-Mental State Examination (MMSE) score. Parecoxib could significantly reduce the concentrations of interleukin-6, but results regarding the changes in tumor necrosis factor-alpha, C-reactive protein, and S100ß levels remained inconsistent. CONCLUSION: Perioperative parecoxib administration is effective in reducing the incidence of POCD and improving the MMSE score compared with control. However, the beneficial effect of parecoxib has been tested only in the Chinese population. Future RCTs in western countries with larger-scale and more comprehensive neurological tests are needed.

The efficacy of virtual reality exposure therapy for PTSD symptoms: A systematic review and meta-analysis.

BACKGROUND: Virtual reality exposure therapy (VRET) for PTSD is an emerging treatment of remarkable promise, but its efficacy and safety are still unclear. Our aim was to investigate the efficacy of VRET for individuals with PTSD, and to identify the potential moderating variables associated with interventions. METHODS: Literature search was conducted via PubMed, Embase, Web of Science, Cochrane Library, PsycInfo, Science Direct, and EBSCO. We identified 18 studies on PTSD including 13 randomized controlled trials (RCTs; 654 participants) and 5 single-group trials (60 participants). RESULTS: The main effects analysis showed a moderate effect size (g = 0.327, 95% CI: 0.105-0.550, p<0.01) for VRET compared to control conditions on PTSD symptoms. Subgroup analysis revealed that the effects of VRET were larger when compared to inactive groups (g = 0.567) than active control groups (g = 0.017). This finding was in agreement with depressive symptoms. A dose-response relationship existed with more VRET sessions showing larger effects. There was a long-range effect of VRET on PTSD symptoms indicating a sustained decrease in PTSD symptoms at 3-month follow-up (g = 0.697) and 6-month follow-up (g = 0.848). The single-group trials analysis revealed that the VRET intervention had a significant effect on PTSD. LIMITATIONS: Many of the combat-related PTSD subjects resulted in uncertainty regarding meta-analytical estimates and subsequent conclusions. CONCLUSIONS: These findings demonstrated that VRET could produce significant PTSD symptoms reduction and supported its application in treating PTSD.

IgD-activated mast cells induce IgE synthesis in B cells in nasal polyps.

BACKGROUND: Although upregulated expression of local IgD has been reported in patients with chronic rhinosinusitis (CRS), its function is unclear. OBJECTIVE: We sought to explore the expression and function of soluble IgD in patients with CRS, particularly CRS with nasal polyps. METHODS: IgD levels in sinonasal mucosa were analyzed by using RT-PCR and ELISA. Numbers and phenotypes of IgD+ cells were studied by means of immunohistochemistry, immunofluorescence, and flow cytometry. HMC-1 cells, a human mast cell line, and mast cells purified from eosinophilic polyps were cultured alone or with naive B cells purified from peripheral blood. The antigen specificity of nasal IgD was investigated by using ELISA. RESULTS: The mRNA expression of immunoglobulin heavy constant delta gene, numbers of IgD+ cells, and protein levels of secretory IgD in sinonasal mucosa were increased in patients with CRS with or without nasal polyps compared with control subjects. Numbers of IgD+ plasmablasts were increased in both eosinophilic and noneosinophilic polyps, whereas numbers of IgD+ mast cells were only increased in eosinophilic polyps. Cross-linking IgD induced serum preincubated HMC-1 cells and polyp mast cells to produce B-cell activating factor, IL-21, IL-4, and IL-13 and to promote IgM, IgG, IgA, and IgE production from B cells. In eosinophilic polyps expression of those B cell-stimulating factors in mast cells and close contact between mast cells and B cells were found. Moreover, positive correlations of total IgD levels with total IgE levels and eosinophilia and upregulation of specific IgD against house dust mites were discovered in eosinophilic polyps. CONCLUSION: IgD-activated mast cells can facilitate IgE production and eosinophilic inflammation in patients with CRS with nasal polyps.

Immune active cells with 4-1BB signal enhancement inhibit hepatitis B virus replication in noncytolytic manner.

Immune active cells (IACs) have been shown to be an alternative immunotherapy for CHB patients. However, there is a practical problem of different expansion rate and function of HBV inhibition as individual variability exists. Our previous studies have confirmed that the proliferation and cytolysis of IACs were significantly up-regulated by engineered cells for costimulatory enhancement (ECCE) delivering a 4-1BBζ activating signal. In this study, we aimed to investigate the contribution of ECCE to IACs from CHB patients. We found that ECCE could enhance larger-scale expansion of IACs and the levels of HBV-markers were reduced prominently with minimal cytolysis, in the indirect system which separated ECCE-IACs and HepG2.2.15 by a 0.4-µm membrane. Furthermore, ECCE-IACs produced a lot of IFN-γ and TNF-α. Blockading them, the inhibition was abrogated. These results provide direct evidence that ECCE-IACs efficiently control HBV replication in a noncytolytic manner, and this effect is mediated by IFN-γ and TNF-α.

The activation and function of IL-36γ in neutrophilic inflammation in chronic rhinosinusitis.

BACKGROUND: Although increased accumulation of neutrophils has been noted in chronic rhinosinusitis (CRS), the function and regulation of neutrophils in CRS are largely unknown. IL-36 family cytokines may play an important role in neutrophilic inflammation. OBJECTIVE: This study sought to investigate the expression and function of IL-36 cytokines in CRS. METHODS: Quantitative RT-PCR, immunohistochemistry, immunofluorescence, and ELISA were used to investigate the expression of IL-36 cytokines and IL-36 receptor (IL-36R) in sinonasal mucosa. The expression of IL-36R on neutrophils in polyps and blood was measured by flow cytometry. Purified blood neutrophils were cultured to investigate the regulation of IL-36R expression. The cleavage of IL-36γ was detected by Western blotting. Dispersed nasal polyp cells were treated with IL-36γ with or without elastase inhibitor and dexamethasone. RESULTS: Neutrophil infiltration and expression of IL-36 cytokines and IL-36R were upregulated in both CRS with and without nasal polyps. IL-36γ was the most abundant isoform and mainly expressed by epithelial cells in CRS. Neutrophils were the principal IL-36R+ cell type in polyps. IL-36R expression was almost absent in blood neutrophils and upregulated by IL-6, IL-1ß, and Dermatophagoides pteronyssinus group 1. Elastase activity was increased in polyps and degraded full-length IL-36γ. Consistently, the levels of cleaved IL-36γ were increased in polyps. Full-length IL-36γ promoted the production of matrix metalloproteinase 9; IL-17A; and chemokine (C-X-C motif) ligands 1, 2, and 8 from dispersed nasal polyp cells, which was abolished by elastase inhibitor. The proinflammatory effect of IL-36γ was not suppressed by dexamethasone. CONCLUSIONS: Increased production and activation of IL-36γ may act on neutrophils and further exaggerate neutrophilic inflammation in CRS.

Efficacy and Safety of Postoperative Pain Relief by Parecoxib Injection after Laparoscopic Surgeries: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: This study aims to evaluate the efficacy and safety of parecoxib injection in pain relief after laparoscopic surgeries. METHODS: A comprehensive literature search based on 4 online databases (PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science) was applied to retrieve all related randomized controlled trials (RCTs). Two independent reviewers screened each article for eligibility according to the predetermined inclusion criteria. The Cochrane Collaboration's tool was applied to evaluate the methodological quality of included studies. A standardized data collection sheet was designed to extract data from included studies. RevMan version 5.3 (The Cochrane Collaboration, Copenhagen, Denmark) was selected to perform meta-analysis. RESULTS: A total of 1,060 participants who were scheduled for gynecological laparoscopic surgery or laparoscopic cholecystectomy (LC) were enrolled in 12 selected RCTs. The methodological qualities of the studies were evaluated as moderate to high. The combined data showed that perioperative parecoxib injection could significantly reduce the proportion of patients who required adjuvant pain relieve after laparoscopic surgeries. Significantly lower pain scores in the parecoxib groups were observed, which proved that preoperative or intraoperative injection of 40 mg parecoxib was more effective than placebo for immediate pain relief after LC. But preoperative injection of 40 mg parecoxib showed no improvement compared with placebo in the management of immediate pain following gynecological laparoscopic surgery. The occurrence of adverse events showed no differences between perioperative parecoxib administration and placebo control. CONCLUSION: Perioperative parecoxib administration was effective in reducing the proportion of patients who required adjuvant pain relief after laparoscopic surgeries without significant adverse events compared with placebo. The effect of parecoxib injection on immediate pain relief remains in question. Future RCTs with larger sample sizes are encouraged.

The Clinical Effect of Acupuncture in the Treatment of Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Purpose. This study aims to determine the clinical efficacy of acupuncture therapy in the treatment of obstructive sleep apnea. Methods. A systematic literature search was conducted in five databases including PubMed, EMBASE, CENTRAL, Wanfang, and CNKI to identify randomized controlled trials (RCTs) on the effect of acupuncture therapy for obstructive sleep apnea. Meta-analysis was conducted using the RevMan version 5.3 software. Results. Six RCTs involving 362 subjects were included in our study. Compared with control groups, manual acupuncture (MA) was more effective in the improvement of apnea/hypopnea index (AHI), apnea index, hypopnea index, and mean SaO2. Electroacupuncture (EA) was better in improving the AHI and apnea index when compared with control treatment, but no statistically significant differences in hypopnea index and mean SaO2 were found. In the comparison of MA and nasal continuous positive airway pressure, the results favored MA in the improvement of AHI; there was no statistical difference in the improvement in mean SaO2. No adverse events associated with acupuncture therapy were documented. Conclusion. Compared to control groups, both MA and EA were more effective in improving AHI and mean SaO2. In addition, MA could further improve apnea index and hypopnea index compared to control.