CircPIAS1 promotes hepatocellular carcinoma progression by inhibiting ferroptosis via the miR-455-3p/NUPR1/FTH1 axis.

BACKGROUND: The role of circRNAs in hepatocellular carcinoma (HCC) progression remains unclear. CircPIAS1 (circBase ID: hsa_circ_0007088) was identified as overexpressed in HCC cases through bioinformatics analysis. This study aimed to investigate the oncogenic properties and mechanisms of circPIAS1 in HCC development. METHODS: Functional analyses were conducted to assess circPIAS1's impact on HCC cell proliferation, migration, and ferroptosis. Xenograft mouse models were employed to evaluate circPIAS1's effects on tumor growth and pulmonary metastasis in vivo. Bioinformatics analysis, RNA immunoprecipitation, and luciferase reporter assays were utilized to elucidate the molecular pathways influenced by circPIAS1. Additional techniques, including RNA pulldown, fluorescence in situ hybridization (FISH), chromatin immunoprecipitation (ChIP), qPCR, and western blotting, were used to further explore the underlying mechanisms. RESULTS: CircPIAS1 expression was elevated in HCC tissues and cells. Silencing circPIAS1 suppressed HCC cell proliferation and migration both in vitro and in vivo. Mechanically, circPIAS1 overexpression inhibited ferroptosis by competitively binding to miR-455-3p, leading to upregulation of Nuclear Protein 1 (NUPR1). Furthermore, NUPR1 promoted FTH1 transcription, enhancing iron storage in HCC cells and conferring resistance to ferroptosis. Treatment with ZZW-115, an NUPR1 inhibitor, reversed the tumor-promoting effects of circPIAS1 and sensitized HCC cells to lenvatinib. CONCLUSION: This study highlights the critical role of circPIAS1 in HCC progression through modulation of ferroptosis. Targeting the circPIAS1/miR-455-3p/NUPR1/FTH1 regulatory axis may represent a promising therapeutic strategy for HCC.

ACSL4 accelerates osteosarcoma progression via modulating TGF-ß/Smad2 signaling pathway.

Osteosarcoma (OS) is a malignant bone sarcoma arising from mesenchymal stem cells. The biological role of Acyl-CoA synthetase long-chain family member 4 (ACSL4), recently identified as an oncogene in numerous tumor types, remains largely unclear in OS. In this study, we investigated the expression of ACSL4 in OS tissues using immunohistochemistry staining (IHC) staining of a human tissue microarray and in OS cells by qPCR assay. Our findings revealed a significant up-regulation of ACSL4 in both OS tissues and cells. To further understand its biological effects, we conducted a series of loss-of-function experiments using ACSL4-depleted MNNG/HOS and U-2OS cell lines, focusing on OS cell proliferation, migration, and apoptosis in vitro. Our results demonstrated that ACSL4 knockdown remarkably suppressed OS cell proliferation, arrested cells in the G2 phase, induced cell apoptosis, and inhibited cell migration. Additionally, a subcutaneous xenograft mice model was established to validate the in vivo impact of ACSL4, revealing ACSL4 silencing impaired tumor growth in the OS xenograft mice. Additionally, we discovered that ACSL4 could regulate the phosphorylation level of Smad2 through cooperative interactions, and treatment with a TGF-ß inhibitor weakened the promoting effects of ACSL4 overexpression. In short, ACSL4 regulated OS progression by modulating TGF-ß/Smad2 signaling pathway. These findings underscore ACSL4 as a promising therapeutic target for OS patients and contribute novel insights into the pathogenesis of OS.

Changes in microcystin concentration in Lake Taihu, 13 years (2007-2020) after the 2007 drinking water crisis.

Since the 2007 water crisis occurred in Lake Taihu, substantial measures have been taken to restore the lake. This study evaluates the effectiveness of these restoration activities. We examined the physicochemical parameters and the distribution of microcystin and Microcystis in both the water column and sediment during the bloom period of May 2020 to October 2020. The mean value of extracellular and intracellular microcystin content was 0.12 µg L-1 and 16.26 µg L-1, respectively. The mean value of microcystin in sediment was 172.02 ng g-1 and peaked in August. The concentration in the water and sediment was significantly lower than the historical average concentration. The abundance of toxigenic Microcystis and total Microcystis in the water column ranged from 2.61 × 102 to 2.25 × 109 copies·L-1 and 8.28 × 105 to 2.76 × 109 copies·L-1, respectively. The proportion of toxic Microcystis in the sediment ranging from 31.2% to 19.12%. The highest and lowest region was Meiliang Bay and Grass-algae type zone, respectively. The copy number of the 16S rRNA gene was 1-4 orders of magnitude higher than that of mcyA gene in populations of Microcystis, indicating that non-toxic Microcystis was the dominant form in the majority of the lake. The abundance of toxic Microcystis in the water column was positively correlated with total phosphorus, PO43--P and pH, while the water temperature played distinct role to the distribution of toxic Microcystis in sediment. Our research indicated phosphorus remains a key factor influencing the toxic Microcystis and microcystins in the water column. pH played distinct roles in the distribution of microcystins in sediment and water column. The increasing water temperature is a threat. Explicit management actions and policies, which take into account nutrient concentrations, pH, and increasing temperatures, are necessary to understand and control the distribution of microcystin and Microcystis in Lake Taihu.

COLEC10 Induces Endoplasmic Reticulum Stress by Occupying GRP78 and Inhibits Hepatocellular Carcinoma.

Collectin subfamily member 10 (COLEC10), a C-type lectin mainly expressed in the liver, is involved in the development of hepatocellular carcinoma (HCC). However, its underlying molecular mechanism in HCC progression remains unknown. In this study, reduced COLEC10 expression in tumor tissues was validated using various HCC cohorts and was associated with poor patient prognosis. COLEC10 overexpression attenuated HCC cell growth and migration abilities in vitro and in vivo. We identified that COLEC10 was a novel interactor of 78-kDa glucose-regulated protein (GRP78), a master modulator of the unfolded protein response in the endoplasmic reticulum (ER). COLEC10 overexpression potentiated ER stress in HCC cells, as demonstrated by elevated expression levels of phosphorylated protein kinase RNA-like ER kinase, phosphorylated inositol-requiring protein 1α, activating transcription factor 4, DNA damage-inducible transcript 3, and X-box-binding protein 1s. The ER in COLEC10-overexpressing cells also showed a dilated and fragmented pattern. Mechanistically, COLEC10 overexpression increases GRP78 occupancy through direct binding by the C-terminal carbohydrate recognition domain in the ER, which released and activated the ER stress transducers protein kinase RNA-like ER kinase and phosphorylated inositol-requiring protein 1α, triggering the unfolded protein response activity. COLEC10-overexpressing HCC cells generated a relatively high reactive oxygen species level and switched to apoptotic cell death under sorafenib-treated conditions. Our study provides the first novel view that COLEC10 inhibits HCC progression by regulating GRP78-mediated ER stress signaling and may serve as a promising therapeutic and prognostic biomarker.

Preliminary evidence for endoscopic surgery combined with postoperative anti-PD-1 immunotherapy in advanced recurrent nasopharyngeal carcinoma.

BACKGROUD: Endoscopic surgery can be used as the main treatment for advanced recurrent nasopharyngeal carcinoma (rNPC). However, there is a huge clinical controversy about the need for consolidated immunotherapy after surgery. METHODS: We performed a retrospective propensity score-matched analysis (1:2) of patients with locally advanced rNPC who underwent endoscopic nasopharyngectomy (ENPG) combined with anti-programmed cell death protein-1 (PD-1) monotherapy or ENPG alone. The survival rate was analyzed by Kaplan-Meier method. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), objective response rate (ORR) and disease control rate (DCR). Potential surgical-related complications and immune-related adverse events (AEs) were also assessed. RESULTS: We recruited 10 patients receiving ENPG plus anti-PD-1 monotherapy and 20 receiving ENPG alone. During the mean follow-up of 23.8 months, a significant improvement in the 2-year PFS was detected in the consolidation immunotherapy group compared to the ENPG alone group (80.0% vs. 40.0%; HR = 0.258; 95% CI: 0.09-0.72; p = 0.04), while the 2-year OS in the consolidation immunotherapy group was not significantly longer than that in the ENPG alone group (90.0% vs. 75.0%; HR = 0.482; 95% CI: 0.08-3.00; p = 0.50). The incidence of surgical-related complications in the consolidation immunotherapy group and ENPG alone group was 70.0 and 60.0%, respectively. Immune-related AEs were similar between the toripalimab arm (75.0%) and the camrelizumab arm (66.7%). Surgical-related complications depend on symptomatic treatments. Immune-related AEs were mild and tolerable. CONCLUSIONS: Consolidation immunotherapy regimen for patients with advanced rNPC after ENPG compared to ENPG alone provides a superior PFS rate with a manageable safety profile.

Chloride intercellular channel 3 suppression-mediated macrophage polarization: a potential indicator of poor prognosis of hepatitis B virus-related acute-on-chronic liver failure.

Patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) are characterized by immune paralysis and susceptibility to infections. Macrophages are important mediators of immune responses can be subclassified into two main phenotypes: classically activated and alternatively activated. However, few studies have investigated changes to macrophage polarization in HBV-related liver diseases. Therefore, we investigated the functional status of monocyte-derived macrophages (MDMs) from patients with mild chronic hepatitis B (n = 226), HBV-related compensated cirrhosis (n = 36), HBV-related decompensated cirrhosis (n = 40), HBV-ACLF (n = 62) and healthy controls (n = 10), as well as Kupffer cells (KCs) from patients with HBV-ACLF (n = 3). We found that during the progression of HBV-related liver diseases, the percentage of CD163+ CD206+ macrophages increased, while the percentage of CD80+ human leukocyte antigen-DR+ macrophages decreased significantly. MDMs and KCs mainly exhibited high CD163+ CD206+ expression in patients with HBV-ACLF, which predicted poor clinical outcome and higher liver transplantation rate. Transcriptome sequencing analysis revealed that chloride intracellular channel-3 (CLIC3) was reduced in patients with HBV-ACLF, indicating a poor prognosis. To further study the effect of CLIC3 on macrophage polarization, human monocytic THP-1 cell-derived macrophages were used. We found that classical and alternative macrophage activation occurred through nuclear factor kappa B (NF-κB) and phosphoinositide 3-kinase/protein kinase B pathways, respectively. CLIC3 suppression inhibited NF-κB activation and promoted the alternative activation. In conclusion, macrophage polarization gradually changed from classically activated to alternatively activated as HBV-related liver diseases progressed. Both CLIC3 suppression and increased alternatively activated macrophage percentage were potential indicators of the poor prognosis of patients with HBV-ACLF.

Dummy Template-Based Molecularly Imprinted Membrane Coating for Rapid Analysis of Malachite Green and Its Metabolic Intermediates in Shrimp and Fish.

A novel malachite green molecularly imprinted membrane (MG-MIM) with specific selectivity for malachite green (MG) and leucomalachite green (LMG) was prepared using a hydrophobic glass fiber membrane as the polymer substrate, methyl violet as a template analog, 4-vinyl benzoic acid as the functional monomer, and ethyleneglycol dimethacrylate as the crosslinking agent. MG-MIM and non-imprinted membrane (NIM) were structurally characterized using scanning electron microscopy, surface area analyzer, Fourier-transform infrared spectrometer and synchronous thermal analyzer. The results showed that MG-MIM possessed a fluffier surface, porous and looser structure, and had good thermal stability. Adsorption properties of MG-MIM were investigated under optimal conditions, and adsorption equilibrium was reached in 20 min. The saturated adsorption capacities for MG and LMG were 24.25 ng·cm-2 and 13.40 ng·cm-2, and the maximum imprinting factors were 2.41 and 3.20, respectively. Issues such as "template leakage" and "embedding" were resolved. The specific recognition ability for the targets was good and the adsorption capacity was stable even after five cycles. The proposed method was successfully applied for the detection of MG and LMG in real samples, and it showed good linear correlation in the range of 0 to 10.0 µg·L-1 (R2 = 0.9991 and 0.9982), and high detection sensitivity (detection limits of MG and LMG of 0.005 µg/kg and 0.02 µg·kg-1 in shrimp, and 0.005 µg/kg and 0.02 µg/kg in fish sample). The recoveries and relative standard deviations were in the range of 76.31-93.26% and 0.73-3.72%, respectively. The proposed method provides a simple, efficient and promising alternative for monitoring MG and LMG in aquatic products.

Acute and chronic toxicity of microcystin-LR and phenanthrene alone or in combination to the cladoceran (Daphnia magna).

Hazardous substances, such as microcystin-LR (MC-LR) and phenanthrene (Phe) are ubiquitous co-contaminants in eutrophic freshwaters, which cause harms to aquatic organisms. However, the risks associated with the co-exposure of aquatic biota to these two chemicals in the environment have received little attention. In this study, the single and mixture toxic effects of MC-LR and Phe mixtures were investigated in Daphnia magna after acute and chronic exposure. Acute tests showed that the median effective concentrations (48 h) for MC-LR, Phe and their mixtures were 13.46, 0.57 and 8.84 mg/L, respectively. Mixture toxicity prediction results indicated that the independent action model was more applicable than the concentration addition model. Moreover, combination index method suggested that the mixture toxicity was concentration dependent. Synergism was elicited at low concentrations of MC-LR and Phe exposure (≤4.04 + 0.17 mg/L), whereas antagonistic or additive effects were induced at higher concentrations. The involved mechanism of antagonism was presumably attributable to the protective effects of detoxification genes activated by high concentrations of MC-LR in mixtures. Additionally, chronic results also showed that exposure to a MC-LR and Phe mixture at low concentrations (≤50 +2 µg/L) resulted in greater toxic effects on D. magna life history than either chemical acting alone. The significant inhibition on detoxification genes and increased accumulation of MC-LR could be accounted for their synergistic toxic effects on D. magna. Our findings revealed the exacerbated ecological hazard of MC-LR and Phe at environmental concentrations (≤50 +2 µg/L), and provided new insights to the potential toxic mechanisms of MC-LR and Phe in aquatic animals.

Serum HBV pregenomic RNA is correlated with Th1/Th2 immunity in treatment-naïve chronic hepatitis B patients.

BACKGROUND AND AIM: Hepatitis B virus (HBV) load and antigens are related to the innate and adaptive immunity of chronic hepatitis B (CHB) patients. As a new HBV biomarker, the role of pregenomic RNA (pgRNA) in host immunity is not known. This study aimed to identify the relationship between serum HBV pgRNA and host immunity in CHB patients. METHODS: Two hundred twenty-five treatment-naïve CHB patients were enrolled. Serum cytokines were measured by cytokine antibody array (Luminex multiplex platform). Th1 (T-helper cell, Th) and Th2 cells were tested by flow cytometry. Serum HBV pgRNA was detected by a reverse transcription-polymerase chain reaction. RESULTS: Serum HBV pgRNA was significantly different among patients in different disease phases and significantly associated with both HBV antigens and antibodies. Serum HBV pgRNA was positively correlated with the HBsAg level (P < .001) and the presence of HBeAg (P < .001). Patients with higher HBcAb levels showed lower serum HBV pgRNA levels (P = .003). Notably, HBsAb positivity was associated with higher levels of serum HBV pgRNA in HBeAg(-) patients (P = .049). Serum HBV pgRNA was positively associated with ALT level, Th2 cell frequency, and related cytokine sCD30 (P < .001, P < .001, and P = .003, respectively), but negatively associated with Th1-related cytokine interleukin (IL)-12P70 and cytotoxic lymphocytes (CTLs) (P = .017 and P < .001, respectively). CONCLUSION: Our study confirmed the relationship between serum HBV pgRNA and host immunity. The results demonstrated that serum HBV pgRNA is positively correlated with Th2 immunity but negatively correlated with Th1 immunity, indicating that it might have a relationship with HBV antigen conversion and CTL immunodeficiency in CHB patients.

Distinct T-cell receptor profiles associated with hepatitis B e antigen seroconversion during entecavir treatment.

BACKGROUND & AIMS: T-cell receptor (TCR) repertoire is ambiguously changed in chronic hepatitis B (CHB) patients during antivirus therapy. We tried to assess TCR repertoire dynamics and its clinical significance upon HBeAg seroconversion in CHB patients. METHODS: Twenty CHB patients undergoing 1-year entecavir (ETV) treatment were enrolled, including 10 complete response (CR) vs 10 non-complete response (NCR) patients based on HBeAg seroconversion at week 48. The TCRß complementarity-determining region 3 (CDR3) of peripheral CD4+ and CD8+ T cells at weeks 0, 12 and 48 was analyzed by unbiased high-throughput sequencing. The TCR repertoire profiles and their correlations with serological parameters were analyzed. RESULTS: The diversity of TCRß repertoires was decreasing in CR patients but increasing in NCR patients. The distribution pattern of TCR repertoires stratified according to clonotype frequencies changed in the opposite direction between CR and NCR patients. Narrow amounts of newly appearing clonotypes in CR patients experienced a more intensive and robust expansion and this phenomenon could occur as early as week 12 for the CD4+ subset but later at week 48 for the CD8+ subset. There existed some CR-exclusive clonotypes with a relatively low but increasing frequency at week 48. The number of unique TCRß clonotypes was positively correlated with the ALT or HBV DNA level in CR patients but showed no or negative correlation in NCR patients. CONCLUSION: Distinct TCR profiles contribute to predicting HBeAg seroconversion in CHB patients during ETV treatment and certain TCRß CDR3 motif may be utilized for CHB immunotherapy in the future.

Association among cytokine profiles of innate and adaptive immune responses and clinical-virological features in untreated patients with chronic hepatitis B.

BACKGROUND: Complete clearance of intracellular viruses depends on effector cells of innate and adaptive immune systems. This study aimed to identify the relationships among antiviral cytokines produced by natural killer (NK) and T cells and clinical-virological characteristics in untreated chronic hepatitis B (CHB) patients. METHODS: We measured antiviral cytokines interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and interleukin-2 (IL-2) produced by T, NK and natural killer T (NKT) cells, respectively, in a cohort with chronic hepatitis B virus (HBV) infection (CHB). We also correlated these cytokines with clinical-virological characteristics using a linear regression model. RESULTS: levels of IFN-γ+ and TNF-α+ CD4+ and CD8+ T cells were significantly higher in immune active (IA) phase than in other phases. Immune tolerant (IT) patients showed the lowest expression of IFN-γ by NK and NKT cells, and TNF-α by NK cells. IFN-γ+, TNF-α+ and IL-2+ CD4+ and CD8+ T cells frequencies were similar between IA and gray zone (GZ) phases. Principal component analysis based on cytokines confirmed that most IT patients significantly differed from inactive carriers (IC) and IA patients, while GZ patients were widely scattered. Multivariate analysis showed both T and NK cells producing IFN-γ and TNF-α, but not IL-2, had significant association with serum alanine aminotransferase (ALT). Moreover, IFN-γ+ NKT cells were associated with HBV DNA, while IFN-γ+ CD4+ and CD8+ T cells were correlated with age. CONCLUSION: HBV clinical phases are characterized by distinct cytokine signatures, which showed relationship to viral features in these untreated CHB patients.

Correlations between cytokines produced by T cells and clinical-virological characteristics in untreated chronic hepatitis B patients.

BACKGROUND: Hepatitis B virus (HBV) replicates non-cytopathically in the hepatocytes and HBV-related diseases are caused by immune-mediated inflammatory events. This study aimed to identify the relationship between clinical-virological characteristics and immunity in untreated chronic hepatitis B (CHB) patients. METHODS: A total of 209 CHB patients were categorized into immune tolerant (IT, n = 17), inactive carrier (IC, n = 20), immune active (IA, n = 120), and gray zone (GZ, n = 72) phases. The quantitative hepatitis B surface antigen (qHBsAg), hepatitis B e antigen (HBeAg), anti-HBeAg (HBeAb), HBV genotype, viral mutant and frequencies of interleukin (IL)-4, IL-17, IL-10 and interferon-gamma (IFN-γ) produced by CD4+ and CD8+ T cells were tested. We also correlated these cytokines with clinical-virological characteristics using a linear regression model. RESULTS: CD8+ T cells frequency were significantly decreased in IT patients. Levels of CD4+ T cells IL-4+ or IL-10+ were strongly negatively associated with qHBsAg titers. The frequency of IFN-γ produced by CD4+ and CD8+ T cells showed significant positive association with age and alanine aminotransferase (ALT) level, while that had negative association with qHBsAg titers. Additionally, the ratios of mutations in the HBV precore (PC) stop codon and basal core promoter (BCP) and the combined mutations were 32.5, 27.2, and 11.3%, respectively. The frequency of CD4+ T cells IL-17+ was higher in patients with a PC mutation than that in patients carrying a wild-type sequence. Finally, little associations among T cell derived IL-4, IL-10, IL-17, and IFN-γ was observed in the current untreated CHB cohort. CONCLUSIONS: Several components of the immune system were correlated with HBV factors that influence an inflammatory process during CHB. Of particular relevance are the significant associations of between CD4+ T cells IL-4+ and qHBsAg level, and between CD4+ T cells IL-17+ and the presence of a mutation in PC.

Endoscopic sequestrectomy for skull base osteoradionecrosis in nasopharyngeal carcinoma patients: a 10­year experience.

BACKGROUND: Skull base osteoradionecrosis is a devastating post-irradiation complication in nasopharyngeal carcinoma patients. We conducted a retrospective analysis to assess the long-term survival and prognostic factors of patients with skull base osteoradionecrosis treated with endoscopic sequestrectomy. METHODS: We enrolled 59 nasopharyngeal carcinoma patients with skull base osteoradionecrosis who underwent endoscopic nasopharyngectomy. The clinical characteristics and outcome at the last follow-up visit were collected. The survival curve and univariate and multivariate survival analysis were analyzed by Kaplan-Meier and Cox proportional hazards model to analyze the potential prognostic factors of overall survival, including age, gender, number of radiation, number of operations, extension of disease (local or extensive), whether the ICA is exposed to the procedure (yes or no) and the hypha status (yes or no) at postoperative pathological examination. RESULTS: The predilection sites of skull base osteoradionecrosis in osteoradionecrosis patients are as follows: the base of the sphenoid bone and sphenoid sinus region, the clivus and petrous apex region including the internal carotid canal and the pterygoid process region (including its medial and lateral pterygoid plates). After surgery, clinical symptoms were alleviated in most patients to varying degrees. By the last follow-up visit, 26 patients had died. Most deaths (24) in the study occurred during the first 2 years. Most patients (24) died of sudden severe hemorrhage. The follow-up period ranged from 1 to 108 months, with a median of 27 months. The 2-year overall survival rate was 54.2%. Multivariate Cox regression analysis showed that the number of radiation (P = 0.026) and age (P = 0.002) were independent risk factors for the overall survival. CONCLUSIONS: Endoscopic sequestrectomy with minimal complications and clear vision is a valuable option for the therapy of skull base osteoradionecrosis in nasopharyngeal carcinoma patients.

Co-infection with hepatitis B virus among tuberculosis patients is associated with poor outcomes during anti-tuberculosis treatment.

BACKGROUND: Tuberculosis (TB) and chronic Hepatitis B virus (HBV) infection are common in China. Fist-line anti-TB medications often produce drug-induced liver injury (DILI). This study sought to investigate whether TB patients with chronic HBV co-infection are more susceptible to liver failure and poor outcomes during anti-TB treatment. METHODS: Eighty-four TB patients developed DILI during anti-TB treatment and were enrolled, including 58 with chronic HBV co-infection (TB-HBV group) and 26 with TB mono-infection (TB group). Clinical data and demographic characteristics were reviewed. The severity of DILI and incidences of liver failure and death were compared. Risk factors of clinical outcomes were defined. RESULTS: The patterns of DILI were similar in both groups. Compared with patients in the TB group, patients in the TB-HBV group who did not receive anti-HBV therapy before anti-TB treatment were more susceptible to Grade-4 severity of DILI (36.2% vs. 7.7%, P = 0.005), liver failure (67.2% vs. 38.5%, P = 0.013) and poor outcomes (37.9% vs. 7.7%, P = 0.005). Age > 50 years (48.1% vs. 22.6%, P = 0.049), cirrhosis (50.0% vs. 15.4%, P = 0.046) and total bilirubin > 20 mg/dl (51.6% vs. 14.8%, P = 0.005) were independent risk factors for the rate of death in the TB-HBV group, and HBV DNA > 20,000 IU/ml had borderline significance (44.1% vs. 20.8%, P = 0.081). In the TB-HBV group, nucleos(t)ide analogues as rescue therapy were not able to reduce short-term death (33.3% vs. 36.8%, P = 0.659) once liver failure had occurred. CONCLUSIONS: Patients on anti-TB therapy with chronic HBV co-infection are more susceptible to developing liver failure and having poor outcomes during anti-TB treatment. Regular monitoring of liver function and HBV DNA level is mandatory. Anti-HBV treatment should be considered in those with high viral levels before anti-TB treatment.

Cumulative sum analysis of the learning curve for endoscopic resection of juvenile nasopharyngeal angiofibroma.

BACKGROUND: To determine the learning curve with cumulative sum analysis for endoscopic resection of juvenile nasopharyngeal angiofibroma (JNA) and investigate whether the surgeon's expertise is a risk factor for recurrence. MATERIALS AND METHODS: We reviewed the medical records of patients with JNA who underwent endoscopic or endoscopic-assisted surgery between 2006 and 2015. We used cumulative sum (Cusum) analysis to plot the learning curve for operation time versus chronological sequence, and verified the Cusum curve by risk-adjusted Cusum (RA-Cusum) analysis. We identified three phases of expertise. The recurrence rate was analyzed using the Kaplan-Meier method and log-rank tests. A multivariable Cox regression analysis was performed to identify the independent risk factors for recurrence. RESULTS: We included 154 JNA patients with a median age of 16 years. The surgeon overcame the learning curve after case 80 with increasing surgical efficiency and competence. The learning curve plotted by Cusum analysis divided the cases into three phases: phase 1, accumulation of initial experience (cases 1-41); phase 2, further accumulation of experience (cases 42-117); and phase 3, mastering the procedure (cases 118-154). Pearson's χ2 tests showed that tumor stage (P = 0.021), blood loss (P = 0.001), operation time (P < 0.001), and phase (P < 0.001) were associated with recurrence. The log-rank test showed that time to recurrence was significantly shorter in phase 1 than in phases 2 and 3. Blood loss and phase were independently prognostic factors for time to recurrence, with P values of 0.023 and 0.009, respectively. The RA-Cusum analysis identified two inflection points of the curve at case 44 and 83, and verified the results of Cusum analysis. CONCLUSION: Surgical experience and competence with endoscopic resection affect the recurrence rate in JNA patients. LEVEL OF EVIDENCE: 4.

Endoscopic Repairs of Sinonasal Cerebrospinal Leaks: Outcome and Prognostic Factors.

OBJECTIVE: The aim of this study was to review the management of sinonasal cerebrospinal fluid (CSF) leaks and outcome of endoscopic repairs and to provide experience regarding leaks at the lateral wall of sphenoid sinus and the posterior wall of frontal sinus. METHODS: Patients who underwent endoscopic repairs of CSF leaks were reviewed. Characteristics of different etiologies were compared, and prognostic factors were analyzed. RESULTS: The study included 144 patients with 150 CSF leaks, in which spontaneous leaks account for 55%. Patients with traumatic leaks were significantly younger than those with spontaneous leaks (P = 0.012), and most traumatic leaks occurred in men (P < 0.001). The computed tomography scan showed an overall accuracy of 86.7%. For 17 leaks at the lateral wall of sphenoid sinus, transnasal (29%), transethmoid (24%), and transpterygoid (47%) approaches were used, with a success rate of 75%. For 11 defects at the posterior wall of the frontal sinus, 2 were managed by draf III surgery, and 3 by trephination-assisted procedure successfully. Success rate for primary repair was 95.6%, reaching 100% after a second repairing. Six leaks failed to be repaired included 4 spontaneous leaks, and 3 occurred at the lateral wall of the sphenoid sinus, 4 occurred in patients with elevated body mass index (BMI), 4 had evidence of raised intracranial pressure (ICP). CONCLUSION: Repair of leaks at lateral sphenoid sinus and posterior frontal sinus could achieve favorable results via selected endoscopic approaches. The failure of repair was associated with inaccessible leak sites, spontaneous leaks, raised ICP, and elevated BMI.

Veritable antiviral capacity of natural killer cells in chronic HBV infection: an argument for an earlier anti-virus treatment.

BACKGROUND: There is limited information on innate immunity, especially natural killer (NK) cell function, in different chronic hepatitis B (CHB) stages. Therefore, we examined whether the clinical staging strategy accurately reflects veritable NK cell immunity. METHODS: A total of 237 eligible CHB patients and 22 healthy controls were enrolled in our study. Demographic and clinical data were collected, and the CHB phases (immune active-IA, immune tolerant phase-IT, inactive CHB-IC, and grey zone-GZ) were classified according to the latest American Association for the Study of Liver Disease guidelines. Peripheral blood mononuclear cells from patients and healthy controls were tested for NK cell frequency, phenotype and function using flow cytometry. RESULTS: A significant decrease in activating receptor NKp44 and NKp46 expression and significant increase of exhaustion molecule Tim-3 expression were observed in NK cells from CHB patients. Reduced cytokine secretion and preserved or elevated cytotoxic function were also observed. Patients in the IT group exhibited comparable cytokine secretion and cytolytic capacity as age-matched IA patients. NK cell anti-viral functions were preserved in GZ patients. Some of the NK cell function in patients who were excluded from treatment by the current treatment guidelines was less compromised than patients who qualified for treatment. CONCLUSION: Our findings provide evidence of veritable NK cell immunity during different natural history phases in treatment-naïve patients with chronic HBV Infection. Chronic HBV infection hindered NK cell function in CHB patients. However, the presumed IT and GZ statuses of CHB patients based on the clinical parameters may not accurately reflect the inner immune status of these patients and should be reconsidered. Some patients excluded from treatment by the current treatment guidelines may be able to be selected as candidates for treatment.

Salvage endoscopic nasopharyngectomy for local recurrent or residual nasopharyngeal carcinoma: a 10-year experience.

BACKGROUND: Our aim was to review the outcomes of endoscopic nasopharyngectomy performed on a large series of patients with residual or recurrent nasopharyngeal carcinomas and to identify the prognostic factors. METHODS: Ninety-one patients with residual (10) and recurrent (81) nasopharyngeal carcinomas who underwent endoscopic nasopharyngectomy were enrolled in our study. Clinical information including gender, age, medical history, symptoms, radiographic findings, tumor stage, treatment, recurrence time, postoperative pathological examination, complications, and outcomes at last follow-up visit was collected. The survival curves and multivariate survival analysis were analyzed using the Kaplan-Meier and Cox proportional hazards model. RESULTS: Our study included 71 men and 20 women with a median age of 51 years. The lesions were staged as follows: rT1, 30; rT2, 13; rT3, 29; and rT4, 19. No serious operative or postoperative complication was observed. The median follow-up period was 23 months (range, 4-109 months). Tumor necrosis was identified in 40 of 91 patients. At the last follow-up, 42 patients were free of disease, 10 were alive with disease, and 39 had died. At 2- and 5-year follow-up, the overall survival rates were 64.8% and 38.3%, respectively; the disease-free survival rates were 57.5% and 30.2%, respectively, for the two periods. Multivariate analysis showed that T classification (P = 0.02) and tumor necrosis (P = 0.024) were independent risk factors. CONCLUSIONS: Endoscopic nasopharyngectomy is a feasible and effective surgical treatment for recurrent and residual nasopharyngeal carcinomas.

Efficient Reductive Decomposition of Perfluorooctanesulfonate in a High Photon Flux UV/Sulfite System.

Hydrated electron (eaq-) induced reduction techniques are promising for decomposing recalcitrant organic pollutants. However, its vigorous reactivity with copresent scavenging species and the difficulty in minimizing the competitive reactions make the proportion of eaq- participating in pollutant decomposition low, reflecting by slow decomposition kinetics. In this study, a high photon flux UV/sulfite system was employed to promote eaq- production. Its feasibility in enhancing a notorious recalcitrant pollutant, PFOS, decomposition was investigated. The effective photon flux utilized for producing eaq- was 9.93 × 10-8 einstein/cm2·s. At initial solution pH 9.2, with DO about 5 mg/L, and at around 25 °C, 98% PFOS was decomposed within 30 min from its initial concentration of 32 µM. The kobs of PFOS decomposition was 0.118 min-1 (7.08 h-1), and about 8-400 folds faster than those obtained in other reductive approaches. In this system, PFOS decomposition showed can tolerate copresent 7 mg N/L of NO3-. Suggested by molecular orbitals and thermodynamic analyses, the mechanisms responsible for PFOS decomposition involve defluorination, desulfonation, and centermost C-C bond scission. By demonstrating a more practical relevant treatment process, the outcomes of this study would be helpful for facilitating future applications of eaq- induced reduction techniques for efficient recalcitrant pollutants decomposition.

Health care workers in Pearl River Delta Area of China are not vaccinated adequately against hepatitis B: a retrospective cohort study.

BACKGROUNDS: Health-care workers' (HCWs) exposure to bodily fluids puts them at risk of hepatitis B virus HBV infection. This study investigated HBV vaccination practices and outcomes in HCWs and assessed postvaccination seroprotection across HCWs in different departments. METHODS: A survey of HCWs in a Chinese public general hospital was carried out with a retrospective cohort of 1420 hospital HCWs (458 males and 962 females). HBV vaccination status (10-µg/dose used) was investigated in the cohort from vaccination records from the period of 1988 to 2008. Blood samples were collected and tested for hepatitis B surface antigen (HBsAg) and HBV antibodies (anti-HBs). RESULTS: The overall vaccination (complete course) and HBsAg carrier rates among HCWs were 40.42 % (574/1420) and 6.13 % (87/1420), respectively. Vaccination rates differed by department, with HCWs in internal medicine (39.5 %) and emergency (42.0 %) departments having particularly low rates. The natural infection rate was 7.53 % (107/1420) among HCWs. HCWs in the department of infectious diseases (vaccination rate, 57.8 %) had the highest rate of antibody produced by natural infection (88.2 %). CONCLUSION: The vaccination rate was a disappointingly low among HCWs in Pearl River Delta Area of China. HCWs working in infectious diseases departments and technicians were at particularly likely to have been infected with HBV. A concerted effort is needed to bring vaccination rates up among Chinese HCWs in Pearl River Delta Area of southern China.