Publications by authors named "Yurong Gu"

42 Publications

Serum HBV pregenomic RNA exhibited opposite associations with NKdim and NKbright cell immunity in treatment-naïve chronic hepatitis B patients.

Biosci Rep 2021 Jul;41(7)

Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Hepatitis B virus (HBV) pregenomic RNA (pgRNA) is a new biomarker that reflects HBV replication, but its relationship with natural killer (NK) cell immunity in chronic hepatitis B (CHB) is unknown. We assessed serum HBV pgRNA levels in 323 CHB patients by reverse transcription-polymerase chain reaction, assessed cytokine production and activation and inhibitory markers of NK cells by flow cytometry, and measured serum cytokines by enzyme-linked immunosorbent assays (ELISAs). Among the different CHB phases, the serum HBV pgRNA level was highest in the immune-tolerant (IT) and immune-active (IA) phases. Regarding NK and NKdim cells, HBV pgRNA was negatively associated with frequencies, but positively associated with NKp44 and NKp46 expression (activation markers). Regarding NKbright cells, serum HBV pgRNA was positively associated with frequency and programmed cell death protein 1 (PD1) expression (inhibitory marker), but negatively associated with NKp44 and NKp46. Serum HBV pgRNA was not associated with NKp30 (activation marker) on NK cells or subsets. Lastly, serum HBV pgRNA was positively correlated with the levels of serum IL-7 and IL-12P40 (NK cell-promoting cytokines) and negatively correlated with serum prostaglandin E2 (PGE2) level (which negatively regulates NK cells). In conclusion, we found varied relationships between serum HBV pgRNA and NK cells and subsets, indicating that HBV pgRNA may play a complicated role in NK cell-related immunity, providing new information on HBV and host immunity.
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http://dx.doi.org/10.1042/BSR20210600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255538PMC
July 2021

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

Ecotoxicol Environ Saf 2021 Sep 12;220:112405. Epub 2021 Jun 12.

State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, 73 East Beijing Road, Nanjing 210008, China. Electronic address:

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.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112405DOI Listing
September 2021

Types of Transnasal Endoscopic Nasopharyngectomy for Recurrent Nasopharyngeal Carcinoma: Shanghai EENT Hospital Experience.

Front Oncol 2020 14;10:555862. Epub 2021 Jan 14.

Department of Otolaryngology, Eye, Ear, Nose and Throat Hospital, Shanghai Medical College of Fudan University, Shanghai, China.

Background: Transnasal endoscopic nasopharyngectomy (TEN) has become increasingly used for recurrent nasopharyngeal carcinoma (rNPC); however, there is no report on the definitive resectable contour for TEN according to the latest staging system for nasopharyngeal carcinoma. The aim of this study was to establish the types of TEN for rNPC.

Materials And Methods: A total of 101 rNPC patients underwent TEN from January 2016 to April 2019 at the authors' institution. TEN was categorized into four types, which included type I (n=40) with resection of the nasopharynx and sinuses; type II (n=10) with lateral extension to the parapharyngeal space; type III (n=40) with lateral extension to the floor of the middle cranial fossa and the infratemporal fossa and superior extension to the orbital apex and the cavernous sinus back to the prevertebral region; and type IV (n=11) with the resection of the involved internal carotid artery following type III. The 2-year overall survival rate (OS) and local recurrence-free survival rate (LRFS) were assessed.

Results: The median time of follow-up was 20 months. Twenty-five patients reoccurred. Nineteen patients died. Independent predictors of outcome on multivariate analysis were recurrent T stage (P = 0.039), types of TEN (P = 0.002) and surgical margin (P = 0.003). The 2-year OS and LRFS was 76.2% and 53.6%, respectively.

Conclusions: The result of TEN in the treatment of rNPC is promising. The types of TEN will provide effective guideline for surgical treatment of rNPC.
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http://dx.doi.org/10.3389/fonc.2020.555862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873878PMC
January 2021

An Immuno-Clinic score model for evaluating T cell immunity and predicting early antiviral therapy effectiveness in chronic hepatitis B.

Aging (Albany NY) 2020 12 26;12(24):26063-26079. Epub 2020 Dec 26.

Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.

We generated an Immuno-Clinic score (ICS) model to evaluate T cell immunity based on the clustering of antiviral cytokines and inhibitory molecules in 229 naïve chronic hepatitis B (CHB) patients. 126 patients receiving antiviral therapy were used to validate the model for predicting antiviral therapy effectiveness. Through receiver-operator characteristic curve analysis, the area under the curve, sensitivity, and specificity of the ICS model were 0.801 (95%CI 0.703-0.900), 0.727, and 0.722, respectively. The cut-off value was 0.442. Re-evaluation of T cell immunity in different phases of CHB showed that patients in the immune tolerant phase had the lowest percentage of ICS-high (15%), while patients in the inactive carrier phase had the highest percentage of ICS-high (92%). Patients in the immune active and gray zone phases had 17% and 56% ICS-high, respectively. Elevation of ICS as early as four weeks after treatment could predict the effectiveness of hepatitis B virus (HBV) DNA loss and normalization of alanine aminotransferase, while eight weeks after treatment could predict HBV surface antigen decline. Thus, this ICS model helps clinicians choose an optimal time for initiating antiviral therapy and predicting its efficacy.
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http://dx.doi.org/10.18632/aging.202274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803537PMC
December 2020

Circular RNA TGFBR2 acts as a ceRNA to suppress nasopharyngeal carcinoma progression by sponging miR-107.

Cancer Lett 2021 02 4;499:301-313. Epub 2020 Nov 4.

Department of Otolaryngology-Head and Neck Surgery, Affiliated Eye, Ear, Nose, and Throat Hospital, Fudan University, Shanghai, 200031, China. Electronic address:

Circular RNAs (circRNAs) act as competing endogenous RNAs, which are involved in the regulation of many types of cancers. They primarily function by sponging microRNAs (miRNAs) and influencing the expression of miRNA by target messenger RNA. However, the role of circRNAs in the progression of nasopharyngeal carcinoma (NPC) remains largely unclear. In this study, differentially expressed miRNAs associated with NPC were screened using microarray analyses, from which miR-107 was identified. Increased miR-107 expression was associated with poor prognosis in NPC, and miR-107 promoted the proliferation and migration of NPC cells. TGFBR2 was identified as the direct target of miR-107, which could reverse its effect on NPC cells. Furthermore, the expression of circTGFBR2 was downregulated in NPC tissue samples, while circTGFBR2 overexpression correlated with favorable prognosis in NPC. Functionally, circTGFBR2 overexpression inhibited the proliferation and migration of NPC cells both in vitro and in vivo. Further analysis showed that circTGFBR2 sponged miR-107, leading to the upregulation of TGFBR2 expression and suppression of NPC progression. Therefore, circTGFBR2 may serve as a novel tumor suppressive factor and potential target for new therapies in NPC patients.
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http://dx.doi.org/10.1016/j.canlet.2020.11.001DOI Listing
February 2021

Salvage Endoscopic Nasopharyngectomy in Recurrent Nasopharyngeal Carcinoma: Prognostic Factors and Treatment Outcomes.

Am J Rhinol Allergy 2021 Jul 5;35(4):458-466. Epub 2020 Oct 5.

Department of Otolaryngology-Head and Neck Surgery, Affiliated Eye Ear Nose and Throat Hospital, Fudan University, Shanghai, China.

Background: This study aimed to investigate the demographics, treatment outcomes, and prognostic factors of salvage endoscopic nasopharyngectomy in recurrent nasopharyngeal carcinoma (NPC).

Methods: We conducted a retrospective analysis of 189 patients who underwent treatment for recurrent NPC from January 2006 to June 2018. The Kaplan-Meier method and log-rank test were used to assess survival rates. A Cox regression model was used for multivariate survival analyses.

Results: We included 132 men and 57 women in the study, with a median age of 51 (range, 25-85) years. The overall 1-, 3-, and 5-year survival rates were 82.2%, 59.5%, and 43.6%, respectively, during a median follow-up of 24 (range, 2-111) months. In subjects over 50 years of age, diabetes, low body mass index (BMI < 20 kg/m), low hemoglobin (<120 g/l) levels, increased neutrophil to lymphocyte ratio (NLR; ≥ 6), advanced T stage (rT3 and rT4), lymph node metastasis, and positive surgical margins were associated with a poor prognosis in terms of overall survival. Cox multivariate regression analyses showed significant differences in age, BMI, NLR, diabetes, T stage, N stage, and tumor necrosis.

Conclusions: In subjects over 50 years of age, diabetes, low BMI, increased NLR, advanced T stage, lymph node metastasis, and tumor necrosis were independent prognostic factors for overall survival.
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http://dx.doi.org/10.1177/1945892420964054DOI Listing
July 2021

Are objective 'findings' the same as subjective 'severity'? A study of the relationship between computed tomography findings and subjective severity in preoperative CRSwNP patients.

Exp Ther Med 2020 Oct 23;20(4):2985-2992. Epub 2020 Jul 23.

Department of Otorhinolaryngology, Eye, Ear, Nose and Throat Hospital of Fudan University, Shanghai 200031, P.R. China.

In pre-surgical patients with chronic rhinosinusitis with nasal polyps (CRSwNPs), positive findings on computed tomography (CT) scans and an exacerbation of symptoms are two possible factors that indicate surgery. However, the relationship between these factors remains unclear. Confirmed CRSwNP patients ready for sinus surgery were consecutively enrolled. The Sino-Nasal Outcome Test 22 (SNOT-22) and visual analog scale (VAS) scoring were completed by these patients, and scores were subjected to factor analysis using a principal component analysis (PCA) to evaluate subjective symptom components related to CRS. Patient CT scores, measured by the Lund-Mackay score (LMS), together with their demographics, medical treatment, and atopy status, were collected and analyzed. A total of 288 patients who met the criteria for CRSwNP and underwent CT scanning prior to surgery in the Eye, Ear, Nose, and Throat Hospital of Fudan University were enrolled. Five components were identified from the PCA of the SNOT-22 results and VAS scores related to subjective symptoms. More severe 'nasal' symptoms (P=0.03; 95% CI, 0.092-1.824), loss of smell and taste (P<0.001; 95% CI, 0.961-1.767) and lower facial pain (P=0.001; 95% CI 1.811 to -0.475), derived from the SNOT-22, were significantly associated with total CT score. For the VAS PCA components, less severe 'ocular' symptoms (P=0.004; 95% CI -1.852 to -0.352), a reduced 'pain' component (P<0.001; 95% CI -2.133 to -0.715), a higher 'nasal' symptom component (P<0.001; 95% CI 0.752-2.257) and, again, loss of smell and taste (P<0.001; 95% CI 0.437-0.811) showed an association with total CT score. 'Allergy-associated symptoms' in both the SNOT-22 and VAS scores and 'loss of smell or taste' and 'hyposmia' were significantly more severe in patients with ethmoid sinus/maxillary sinus (E/M) ratios of >2.59 compared with patients with E/M ratios <2.59. Loss of smell and taste alone was correlated with the LMS in patients with highly positive CT scores. The present study demonstrated associations between several subjective symptoms and objective severity in preoperative CRSwNP patients. Nasal symptoms, including olfaction loss, were correlated positively with CT scores, while ocular- and pain-related symptoms showed an opposite pattern. However, this relationship was not confirmed in patients with highly positive CT scores. A subset analysis confirmed, in terms of symptoms, the value of the E/M ratio for indicating eosinophilic chronic rhinosinusitis.
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http://dx.doi.org/10.3892/etm.2020.9032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444383PMC
October 2020

Synergetic enhancement toxicity of copper, cadmium and microcystin-LR to the Ceratophyllum demersum L.

Toxicon 2020 Oct 14;186:151-159. Epub 2020 Aug 14.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, 163 Xianlin Avenue, Nanjing, 210023, China. Electronic address:

Heavy metals and microcystins commonly co-exist in water bodies with cyanobacteria, and have been shown to affect aquatic plants. However, their combined effects remain largely unknown. In this study, the toxic effects of copper (Cu) and cadmium (Cd) on Ceratophyllum demersum L. were characterized in the presence of microcystin-LR (MC-LR). The results showed that the bioaccumulation of MC-LR and Cu/Cd in C. demersum was significantly increased by the interaction between MC-LR and Cu/Cd. The combined toxicity assessment results suggested that the toxicities of Cu or Cd to C. demersum would be largely exacerbated by MC-LR, which could be the results of increased bioaccumulation of the pollutants. Cu, Cd and MC-LR, as well as their mixture, significantly decreased plant fresh weight and total chlorophyll content of C. demersum, especially at their high concentrations. The antioxidative system was activated to cope with the adverse effects of oxidative stress. Antioxidant enzyme activities were significantly stimulated by Cu, Cd and MC-LR, as well as their mixture. However, the decreased superoxide dismutase (SOD) and glutathione reductase (GR) activities were observed when exposed to relative high concentrations of Cu or Cd together with MC-LR of 5 μg L. MC-LR brought more stress to the antioxidative system, which is another possible explanation for the synergistic effect. Our findings highlight increased ecological risks of the co-contamination of heavy metals and harmful cyanobacteria.
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http://dx.doi.org/10.1016/j.toxicon.2020.08.008DOI Listing
October 2020

Occurrence and risk assessment of microcystin and its relationship with environmental factors in lakes of the eastern plain ecoregion, China.

Environ Sci Pollut Res Int 2020 Dec 10;27(36):45095-45107. Epub 2020 Aug 10.

State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, 73 East Beijing Road, Nanjing, 210008, China.

The frequent occurrence of microcystins (MCs) in freshwater poses serious threats to the drinking water safety and health of human beings. Although MCs have been detected in individual fresh waters in China, little is known about their occurrence over a large geographic scale. An investigation of 30 subtropical lakes in eastern China was performed during summer 2018 to determine the MCs concentrations in water and their possible risk via direct water consumption to humans, and to assess the associated environmental factors. MCs were detected in 28 of 30 lakes, and the highest mean MCs concentrations occurred in Lake Chaohu (26.7 μg/L), followed by Lake Taihu (3.11 μg/L). MC-LR was the primary variant observed in our study, and MCs were mainly produced by Microcystis, Anabaena (Dolicospermum), and Oscillatoria in these lakes. Replete nitrogen and phosphorus concentrations, irradiance, and stable water column conditions were critical for dominance of MC-producing cyanobacteria and high MCs production in our study. Hazard quotients indicated that human health risk of MCs in most lakes was at moderate or low levels except Lakes Chaohu and Taihu. Nutrient control management is recommended to decrease the likelihood of high MCs production. Finally, we recommend the regional scale thresholds of total nitrogen and total phosphorus concentrations of 1.19 mg/L and 7.14 × 10 mg/L, respectively, based on the drinking water guideline of MC-LR (1 μg/L) recommended by World Health Organization. These targets for nutrient control will aid water quality managers to reduce human health risks created by exposure to MCs.
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http://dx.doi.org/10.1007/s11356-020-10384-0DOI Listing
December 2020

A novel nomogram to predict survival in patients with recurrent nasopharyngeal carcinoma after salvage endoscopic surgery.

Oral Oncol 2020 12 23;111:104922. Epub 2020 Jul 23.

Department of Otolaryngology-Head and Neck Surgery, Affiliated Eye Ear Nose and Throat Hospital, Fudan University, Shanghai 200031, China. Electronic address:

Objectives: To develop and validate a nomogram to predict survival in patients with recurrent nasopharyngeal carcinoma (NPC) after salvage endoscopic surgery.

Materials And Methods: A total of 229 eligible patients with recurrent NPC were divided into training (n = 115) and validation (n = 114) cohorts. A multivariate Cox proportional risk regression model was used to identify significant prognostic factors for overall survival (OS) in the training cohort. A nomogram was then developed based on the regression model. The performance of the nomogram was assessed with regard to discrimination and calibration. Patients were divided into low-risk or high-risk groups based on the risk scores derived from the nomogram. Furthermore, decision curve analysis (DCA) was used to assess the clinical utility of the nomogram.

Results: Six significant predictors were identified: diabetes mellitus, body mass index (BMI), neutrophil-to-lymphocyte ratio (NLR), T stage, lymph node metastasis, and tumor necrosis. The nomogram incorporating these six predictors demonstrated favorable discrimination and calibration in the training cohort, with a C-index of 0.746 (95% confidence interval [CI] 0.656-0.836), which was subsequently confirmed in the validation cohort (C-index 0.768 [95% CI 0.675-0.861]). Furthermore, the nomogram successfully distinguished patients into low- and high-risk groups. DCA indicated that the nomogram was clinically useful.

Conclusions: The novel nomogram demonstrated its potential as an individual tool to predict survival in patients with recurrent NPC after salvage endoscopic surgery.
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http://dx.doi.org/10.1016/j.oraloncology.2020.104922DOI Listing
December 2020

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

BMC Infect Dis 2020 Jul 14;20(1):509. Epub 2020 Jul 14.

Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University, 600 Tian He Rd, Guangzhou, 510630, China.

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.
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http://dx.doi.org/10.1186/s12879-020-05233-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362653PMC
July 2020

Tension Pneumocephalus from Endoscopic Endonasal Surgery: A Case Series and Literature Review.

Ther Clin Risk Manag 2020 19;16:531-538. Epub 2020 Jun 19.

Department of Otolaryngology-Head and Neck Surgery, Affiliated Eye Ear Nose and Throat Hospital, Fudan University, Shanghai 200031, People's Republic of China.

Purpose: Tension pneumocephalus (TP) caused by endoscopic endonasal surgery is a serious complication. We report four cases of TP caused by endoscopic surgery and review other cases in the literature, with special attention devoted to symptoms, imaging features, and therapeutic approaches.

Methods: A retrospective chart review of patients who experienced TP caused by endoscopic surgery in our institution between 2015 and 2018 was performed. Additionally, the MEDLINE database was searched for all case series or reports of TP caused by endoscopic surgery.

Results: Eighteen articles were identified for review, including four cases from the authors' institution; ultimately, 26 cases were included in the present study. The main symptoms of TP were headache and a change in mental status. Cerebrospinal fluid (CSF) leakage was reported in 21 of the 26 patients (80.8%). Eight of the 26 patients (30.8%) presented with the "Mount Fuji sign" imaging feature. Twenty-four patients were treated with surgical intervention for TP (endoscopic multilayer closure of skull base defect, cranial burr hole, or bifrontal craniotomy). In addition, the present study is the first to report two patients with TP who were successfully treated conservatively.

Conclusion: The therapeutic method for treating TP should depend on the degree of the mass effect and clinical symptoms. When patients with TP present with obvious symptoms of CSF leakage and intracranial hypertension, urgent surgical multilayer repair of the skull base defects and/or release of the intracranial pressure are keys to treating these patients. However, conservative treatment under close observation is also feasible when the related symptoms are not overtly obvious.
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http://dx.doi.org/10.2147/TCRM.S258890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311094PMC
June 2020

Quality of Life Following Salvage Endoscopic Nasopharyngectomy in Patients With Recurrent Nasopharyngeal Carcinoma: A Prospective Study.

Front Oncol 2020 17;10:437. Epub 2020 Apr 17.

Department of Otolaryngology-Head and Neck Surgery, Affiliated Eye Ear Nose and Throat Hospital, Fudan University, Shanghai, China.

This study aimed to assess the effect of endoscopic nasopharyngectomy in patients with recurrent nasopharyngeal carcinoma (NPC) on site-specific and sinonasal-related quality of life (QoL) before and after surgery using validated instruments. Consecutive adult patients with recurrent NPC, who were treated via salvage endoscopic nasopharyngectomy, were prospectively enrolled at a single institution from January 2018 to December 2019. Each patient completed the Anterior Skull Base Questionnaire (ASBQ) and the 22-Item Sino-Nasal Outcome Test (SNOT-22) preoperatively, and then at regular intervals after surgery to assess their perceived QoL. Forty patients fulfilled the inclusion criteria. The median follow-up was 12 months (range, 2-24 months). Overall scores on the ASBQ and SNOT-22 at 3 or 12 weeks after surgery decreased significantly compared with before surgery ( < 0.05). At 6 months and 1 year postoperatively, there was no significant difference from the preoperative score. Subtotal resection was associated with worse overall ASBQ scores at 6 months and 1 year after endoscopic nasopharyngectomy ( < 0.05). Worse QoL was also associated with advanced T stage (rT3 and rT4) and pathological World Health Organization type III. Sex, age (<50 years), tumor necrosis, lymph node metastasis, and use of a nasoseptal flap approach did not impact postoperative QoL. Site-specific and sinonasal-related QoL, measured using validated tools, demonstrated an overall maintenance of postoperative compared with preoperative QoL. Endoscopic endonasal resection is a valuable management choice in patients with recurrent NPC. In addition, subtotal resection was an important factor that negatively influenced postoperative QoL; as such, gross-total resection should be attempted in all patients to optimize QoL after surgery.
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http://dx.doi.org/10.3389/fonc.2020.00437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182010PMC
April 2020

Association between effective hepatic blood flow and the severity and prognosis of hepatitis B virus-related acute on chronic liver failure.

Eur J Gastroenterol Hepatol 2021 Feb;32(2):246-254

Department of Infectious Diseases.

Background: Hepatic inflammation resulted in hepatocyte necrosis and microcirculatory dysfunction in acute on chronic liver failure (ACLF) with cirrhosis or not. The influence of effective hepatic blood flow (EHBF) on the severity of liver failure has not been fully elucidated.

Aim: The aim of this study was to assess the correlation between the EHBF and the severity and the prediction of 90-day mortality rate of hepatitis B virus-related ACLF (HBV-ACLF).

Methods: In this retrospective study, patients hospitalized for HBV-ACLF or decompensated cirrhosis and who underwent an indocyanine green (ICG) clearance test between June 2016 and July 2018 were enrolled. EHBF was measured by the ICG clearance test and patients were categorized into the ACLF without cirrhosis (HBV-ACLF-no-Cir), ACLF with cirrhosis (HBV-ACLF-Cir) and decompensated cirrhosis (HBV-De-Cir).

Results: A total of 522 patients (HBV-ACLF-no-Cir: 84, HBV-ACLF-Cir: 111 and HBV-De-Cir: 327) were enrolled. The mean EHBF in the HBV-De-Cir was significantly higher than that in the HBV-ACLF-no-Cir and HBV-ACLF-Cir (0.36 vs. 0.21 vs. 0.20 L/min, P < 0.001). EHBF was significantly correlated with the total bilirubin, prothrombin activity and model for end-stage liver disease (MELD) in the HBV-ACLF-no-Cir. The predicted 90-day mortality rate using the MELD, EHBF, ICG-retention rate at 15 min (R15%) and EHBF-R15% scores were similar. The sensitivity and specificity of the EHBF varied between 68.5-80.2% and 45.8-73.7%, respectively. The EHBF-MELD score had the highest specificity.

Conclusion: EHBF was significantly lower in the patients with ACLF compared to decompensated cirrhosis. The EHBF were closely related to the severity of HBV-ACLF and can be used for predicting the 90-day mortality rate of HBV-ACLF.
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http://dx.doi.org/10.1097/MEG.0000000000001721DOI Listing
February 2021

CCL14 is a prognostic biomarker and correlates with immune infiltrates in hepatocellular carcinoma.

Aging (Albany NY) 2020 01 12;12(1):784-807. Epub 2020 Jan 12.

Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

C-C motif chemokine ligand 14 (CCL14) is a chemokine promoting the activation of immune cells. However, the relationship between CCL14 expression, tumor immunity, and prognosis in Hepatocellular Carcinoma (HCC) remain unclear. CCL14 expression and its influence on tumor prognosis were analyzed by the ONCOMINE, Tumor Immune Estimation Resource (TIMER) and Kaplan-Meier plotter. The relationship between CCL14 expression and tumor immunity were analyzed by TIMER and Gene Expression Profiling Interactive Analysis (GEPIA). CCL14 expression was significantly lower in several human cancers, including HCC, than in corresponding normal tissues. CCL14 expression in HCC tissues correlated with prognosis. Low CCL14 expression associated with poorer overall survival, disease-specific survival, progression-free survival, and relapse-free survival in multiple cohorts of HCC patients, particularly at early disease stages (stage 1+2 or grade 2). CCL14 showed strong correlation with tumor-infiltrating B cells, CD4 and CD8 T cells, macrophages, neutrophils, and dendritic cells. CCL14 expression in HCC negatively correlated with expression of several immune cell markers, including exhausted T cell markers, PD-1, TIM-3 and CTLA-4, suggesting its role in regulating tumor immunity. These findings demonstrate that CCL14 is a potential prognostic biomarker that determines cancer progression and correlated with tumor immune cells infiltration in HCC.
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http://dx.doi.org/10.18632/aging.102656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6977663PMC
January 2020

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

J Med Virol 2020 03 21;92(3):317-328. Epub 2019 Nov 21.

Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

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.
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http://dx.doi.org/10.1002/jmv.25612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004183PMC
March 2020

A minimally invasive endoscopic transnasal retropterygoid approach to the upper parapharyngeal space: anatomic studies and surgical implications.

Int Forum Allergy Rhinol 2019 11 1;9(11):1263-1272. Epub 2019 Oct 1.

Department of Otolaryngology, Eye, Ear, Nose, and Throat Hospital, Shanghai Medical College of Fudan University, Shanghai, China.

Background: Surgery remains the mainstay of treatment for lesions in the parapharyngeal space. However, gaining access to the parapharyngeal space is often challenging. In this study we aim to describe a minimally invasive technique of approaching the upper parapharyngeal space through an endoscopic transnasal retropterygoid approach, based on anatomic studies and surgeries.

Methods: Six fresh human cadaver heads were prepared for anatomic study at the Surgical Neuroanatomy Laboratory of the Center for Cranial Base Surgery within the Department of Neurological Surgery at the University of Pittsburgh School of Medicine. Three clinical cases seen in the Department of Otolaryngology, Eye, Ear, Nose, and Throat Hospital, Shanghai Medical College of Fudan University, were used to illustrate the technique and feasibility of this approach and to assess its indications, advantages, and drawbacks.

Results: The medial pterygoid plate is the primary landmark of the endoscopic transnasal retropterygoid approach to the upper parapharyngeal space. Access to the upper parapharyngeal space could be obtained by removing the mucosa on the medial pterygoid plate and the mucosa below the pharyngeal orifice of the Eustachian tube. The 3 patients in our study tolerated the procedure well and had no serious complications after surgery.

Conclusion: The anatomic data and clinical cases in this study confirm that an endoscopic transnasal retropterygoid approach is a feasible and effective surgical treatment for selected tumors in the upper parapharyngeal space.
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http://dx.doi.org/10.1002/alr.22437DOI Listing
November 2019

Quantative HBsAg level correlates dendritic cells maturation in chronic hepatitis B patients.

Clin Res Hepatol Gastroenterol 2020 06 23;44(3):321-328. Epub 2019 Aug 23.

Department of Infectious Disease, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Liver Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. Electronic address:

Background: In order to better understand the role of Dendritic cells (DCs) in Chronic Hepatitis B (CHB), we investigated the frequencies and maturation markers on DCs in CHB patients and its change during entecavir treatment.

Methods: Twenty-six CHB patients on anti-virus treatment for 48 weeks were included in this study. Patients' blood samples were collected on every 3 months since starting treatment. Samples on baseline and after 48 weeks treatment were examined using flow-cytometry to investigate frequencies and maturation markers of DCs.

Results: The frequencies of myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) were lower in CHB patients than healthy controls on baseline. pDCs frequencies and mDCs maturation markers expression were increased after entecavir (ETV) treatment. Patients with higher baseline HBsAg levels showed a poorer maturation status than those with low baseline HBsAg levels, regardless of changes in HBsAg levels after treatment.

Conclusions: Entecavir treatment could restore the decreased DCs frequencies in CHB patients and improve DCs maturation levels. Baseline HBsAg level is an important factor that affecting DCs.
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http://dx.doi.org/10.1016/j.clinre.2019.07.016DOI Listing
June 2020

Degradation of tetrabromobisphenol a by ozonation: Performance, products, mechanism and toxicity.

Chemosphere 2019 Nov 27;235:701-712. Epub 2019 Jun 27.

School of Civil and Environmental Engineering, Harbin Institute of Technology, Shenzhen, 518055, China.

This study systematically investigated the performance of ozonation on tetrabromobisphenol A (TBBPA) degradation under different ozone dosages (5.21-83.33 μmoL/L), initial solution pH (3.0-11.0) and temperatures (10-50 °C). At the same time, the generations of inorganic products (bromide ion and bromate) under different experimental conditions were evaluated and the organic products were also identified. Then, the possible mechanism was proposed and verified by the quantum chemical calculation. In addition, variations and controlling of the toxicity were also analyzed, including acute toxicity, chronic toxicity and genotoxicity. Ozonation was proved to be an efficient and promising technology for removing TBBPA from water. TBBPA of 1.84 μmoL/L could be completely degraded within 5 min under the ozone dosage of 41.67 μmoL/L in wide ranges of pH (3.0-11.0) and temperature (10-40 °C). During the degradation of TBBPA, over 65% of the average bromine ion was detected and nine products were identified. The proposed degradation pathways verified that TBBPA might undergo addition and stepwise oxidative debromination, the hydrogen extraction, and the deprotonation. The results of toxicity testing showed that ozonation could effectively control the acute and chronic toxicity of the water samples, although the toxicity increased in the initial reaction stage due to the accumulation of more toxic intermediates.
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http://dx.doi.org/10.1016/j.chemosphere.2019.06.204DOI Listing
November 2019

The Clinical Effect of Arthroscopic Rotator Cuff Repair techniques: A Network Meta-Analysis and Systematic Review.

Sci Rep 2019 03 11;9(1):4143. Epub 2019 Mar 11.

Department of Orthopedics, the second affiliated hospital of Nanchang university, Nanchang, Jiangxi, China.

Rotator cuff tears are common and are associated with shoulder pain, disability, and dysfunction. Previous studies that have reported different arthroscopic techniques are controversial. A network meta-analysis with indirect and direct evidence was performed to compare the effectiveness of arthroscopic techniques for the treatment of rotator cuff tears. PUBMED, the Cochrane Register of Controlled Trials, EMBASE and Scopus were searched based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, and related studies that evaluated arthroscopic techniques for the treatment of rotator cuff tears were identified in May 2018. The primary outcome measure was the retear rate. The secondary outcome measures included the constant score and the range of motion (forward flexion and external rotation). Twenty-one trials comprising 1815 shoulders were included in the study. This study indicated that single-row (SR) repair resulted in a higher retear rate than suture bridge (SB) and double-row (DR) repairs. Moreover, the SR and DR repairs resulted in higher incidences of retear than SB repair. The ranking of the treatments based on the constant score and external rotation was SB repair, SR repair and DR repair, whereas the treatment ranking according to forward flexion was SB repair, DR repair and SR repair. In summary, this network meta-analysis provides evidence that SB repairs might be the best choice to improve the postoperative recovery of function and decrease the retear rate.
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http://dx.doi.org/10.1038/s41598-019-40641-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411857PMC
March 2019

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

BMC Infect Dis 2019 Mar 4;19(1):216. Epub 2019 Mar 4.

Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tian He Rd., Guangzhou, 510630, China.

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.
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http://dx.doi.org/10.1186/s12879-019-3853-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398217PMC
March 2019

Quality of recovery in patients undergoing endoscopic sinus surgery after general anesthesia: total intravenous anesthesia vs desflurane anesthesia.

Int Forum Allergy Rhinol 2019 03 19;9(3):248-254. Epub 2018 Nov 19.

Department of Anesthesiology, Eye Ear Nose and Throat Hospital, Fudan University, Shanghai, China.

Background: For sinus surgery, some centers favor total intravenous anesthesia (TIVA) over inhalation anesthesia. However, whether TIVA affects the patient's perceived quality of recovery remains unclear. This study used the Quality of Recovery-40 questionnaire (QoR-40) to compare patient recovery between surgical patients who received TIVA and those who received desflurane (DES) anesthesia.

Methods: Eighty patients (20 to 65 years old) undergoing endoscopic sinus surgery were prospectively enrolled and randomized to either the TIVA (propofol and remifentanil infusion) or DES (desflurane inhalation and remifentanil infusion) group. The QoR-40 was administered before surgery, at 6 hours after surgery, and on postoperative day 1 (POD1). Incidence of nausea and vomiting, remifentanil consumption, blood loss, and pain treatment were recorded. The influence of lesion extent (indexed as Lund-Mackay [LM] score) on recovery quality was also assessed.

Results: Forty patients were randomized into the TIVA group, and 40 patients were randomized into the DES group. The QoR-40 score at 6 hours after surgery was significantly higher in the TIVA group compared with the DES group (188.2 vs 182.6, respectively; p = 0.049), indicating a better quality of recovery in the TIVA group. TIVA resulted in less blood loss (p < 0.0001). A high LM score (≥12) was associated with lower QoR-40 scores at 6 hours after surgery (180.2 vs 187.2, p = 0.028) and on POD1 (181.5 vs 190.3, p = 0.003).

Conclusion: This study shows that the quality of recovery for endoscopic sinus surgery patients was better with TIVA than with desflurane anesthesia. A high LM score was related to poorer recovery quality.
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http://dx.doi.org/10.1002/alr.22246DOI Listing
March 2019

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

Int J Clin Oncol 2019 Mar 9;24(3):248-255. Epub 2018 Nov 9.

Department of Otolaryngology, Eye Ear Nose and Throat Hospital, Shanghai Medical College, Fudan University, 83 Fenyang Road, Shanghai, People's Republic of China.

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.
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http://dx.doi.org/10.1007/s10147-018-1354-8DOI Listing
March 2019

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

BMC Infect Dis 2018 07 3;18(1):295. Epub 2018 Jul 3.

Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, 600, Tianhe Road, Guangzhou, 510630, China.

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.
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http://dx.doi.org/10.1186/s12879-018-3192-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029116PMC
July 2018

Rapid and high-capacity adsorption of PFOS and PFOA by regenerable ammoniated magnetic particle.

Environ Sci Pollut Res Int 2018 May 6;25(14):13813-13822. Epub 2018 Mar 6.

Shenzhen Key Laboratory of Water Resource Utilization and Environmental Pollution Control, Harbin Institute of Technology Shenzhen Graduate School, Shenzhen, 518055, People's Republic of China.

Adsorption is well accepted as an effective method for perfluorinated compounds' (PFCs) removal from water among various conventional methods. However, development of adsorbents that combine good performance of PFC removal and regenerability has not yet been realized. This work demonstrated the fabrication and application of an ammoniated magnetic adsorbent for efficient and economical PFOS and PFOA removal. Functional ammonium groups and γ-FeO were effectively incorporated in the particle with the proposed method. These fabricated magnetic particles presented superior adsorption performance for PFOS and PFOA with short equilibrium time of 120 min and high adsorption capacity. The isotherms revealed that the adsorption process belonged to multilayer sorption with their intricate interactions including anion exchange and hydrophobic interaction. The magnetic particle maintained its removal efficacy over a wide pH range of 3-9 or with coexisting substances. Moreover, the regeneration and reuse of the magnetic particle were successfully carried out with PFOS and PFOA removal efficiency sustained higher than 80% in 15 consecutive treatment cycles. Along with the efficient adsorption and easy separation of adsorbents, we expect that this ammoniated magnetic particle can serve as an excellent alternative for PFOS and PFOA removal from water.
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http://dx.doi.org/10.1007/s11356-018-1578-1DOI Listing
May 2018

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

Surg Endosc 2018 07 24;32(7):3181-3191. Epub 2018 Jan 24.

Department of Otorhinolaryngology, Eye, Ear, Nose, and Throat Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, China.

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 χ 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.
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http://dx.doi.org/10.1007/s00464-018-6035-1DOI Listing
July 2018

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

J Craniofac Surg 2018 Jan;29(1):182-187

Department of Otorhinolaryngology.

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.
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http://dx.doi.org/10.1097/SCS.0000000000004175DOI Listing
January 2018

Synergistic effect of farnesyl transferase inhibitor lonafarnib combined with chemotherapeutic agents against the growth of hepatocellular carcinoma cells.

Oncotarget 2017 Dec 26;8(62):105047-105060. Epub 2017 Oct 26.

Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Hepatocellular carcinoma (HCC) is a common and deadly cancer worldwide and is often refractory to chemotherapy due to the development of multidrug resistance. Lonafarnib is an orally active and potent non-peptidomimetic inhibitor of farnesyl transferase. Here, using HCC cell models, we demonstrated that lonafarnib inhibited tumor proliferation and reduced the activity of mitogen-activated protein kinases pathways. In addition, lonafarnib caused G1 to S phase arrest through the downregulation of Cyclin D1, CDK6 and SKP2, while it induced cellular apoptosis by promoting the cleavage and activation of Caspase-3 and PARP. When combined with doxorubicin and sorafenib, lonafarnib was able to increase the sensitivity of HCC cells to chemotherapy. Furthermore, we also constructed ABCB1-overexpressing HCC cells and found that lonafarnib decreased chemoresistance by inhibiting ABCB1-mediated drug efflux activity. These results suggest that lonafarnib may be a promising synergistic agent for improving the treatment of drug-resistant HCC.
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http://dx.doi.org/10.18632/oncotarget.22086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5739619PMC
December 2017

Diverse correlations between fibrosis-related factors and liver stiffness measurement by transient elastography in chronic hepatitis B.

Eur J Gastroenterol Hepatol 2018 Feb;30(2):217-225

Background: Several fibrosis-related factors influence liver stiffness measurements (LSM); however, these changes have not been investigated in the context of the various disease stages of chronic hepatitis B (CHB).

Aim: The aim of this study was to assess the correlations between fibrosis-related factors and LSM in different disease stages of CHB.

Patients And Methods: Patients with mild CHB (n=305) and cirrhotic hepatitis B (cirrhotic HB) (n=137) were compared with determine the relationship between LSM and fibrosis-related factors including parameters of liver inflammation [aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (Tbil)], albumin, globulin, peripheral blood cells (neutrophil granulocytes, red blood cells, platelets), abdominal ultrasound B-scan parameters including right liver thickness, portal vein inradium, diameter of spleen (DS), thickness of spleen (TS), and splenic vein inradium (SV).

Results: In patients with mild CHB, LSM was correlated strongly with ALT (r=0.3534, P<0.0001), AST (r=0.3976, P<0.0001), and ALT+AST (r=0.3760, P<0.0001). LSM was correlated closely with Tbil (r=0.2237, P<0.0001), albumin (r=-0.3126, P<0.0001), albumin/globulin (r=-0.3086, P<0.0001), SV (r=0.3317, P<0.0001), DS (r=0.4157, P<0.0001), and spleen volume (DS×TS) (r=-0.4399, P<0.0001). Red blood cells were correlated negatively with LSM in both mild CHB and cirrhotic HB patients (r=-0.1981, P=0.0203; r=-0.1593, P=0.0053). LSM was not correlated with age, peripheral blood cell parameters, right liver thickness, portal vein inradium, or TS in mild CHB or cirrhosis HB patients. However, in patients with cirrhotic HB, LSM values were not correlated significantly with other fibrosis-related factors, except for Tbil (r=0.2272, P=0.0076).

Conclusion: Our findings suggest that the magnitude of these correlations differs significantly between mild CHB and cirrhotic HB patients.
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http://dx.doi.org/10.1097/MEG.0000000000001023DOI Listing
February 2018

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

J Transl Med 2017 10 31;15(1):220. Epub 2017 Oct 31.

Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, 510630, China.

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.
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http://dx.doi.org/10.1186/s12967-017-1318-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5663047PMC
October 2017