[Oncologic outcomes of surgical treatments of advanced sinonasal malignancies].

Objective: To investigate the prognoses of advanced (T3-T4) sinonasal malignancies (SNM). Methods: The clinical data of 229 patients with advanced (T3-4) SNM who underwent surgical treatments in the First Affiliated Hospital of Sun Yat-sen University from 2000 to 2018 were retrospectively analyzed, including 162 males and 67 females, aged (46.8±18.5) years old. Among them, 167 cases received endoscopic surgery alone, 30 cases received assisted incision endoscopic surgery, and 32 cases received open surgery. The Kaplan-Meier method was used to estimate the 3-year and 5-year overall survival (OS) and event-free survival (EFS). Univariate and multivariate Cox regression analyses were performed to explore significant prognostic factors. Results: The 3-year and 5-year OS were respectively 69.7% and 64.0%. The median OS time was 43 months. The 3-year and 5-year EFS were respectively 57.8% and 47.4%. The median EFS time was 34 months. The 5-year OS of the patients with epithelial-derived tumors was better than that of the patients with mesenchymal-derived tumors and malignant melanoma (5-year OS was respectively 72.3%, 47.8% and 30.0%, χ2=36.01, P<0.001). Patients with microscopically margin-negative resection (R0 resection) had the best prognosis, followed by macroscopically margin-negative resection (R1 resection), and debulking surgery was the worst (5-year OS was respectively 78.4%, 55.1% and 37.4%, χ2=24.63, P<0.001). There was no significant difference in 5-year OS between the endoscopic surgery group and the open surgery group (65.8% vs. 53.4%, χ2=2.66, P=0.102). Older patients had worse OS (HR=1.02, P=0.011) and EFS (HR=1.01, P=0.027). Patients receiving adjuvant therapy had a lower risk of death (HR=0.62, P=0.038). Patients with a history of nasal radiotherapy had a higher risk of recurrence (HR=2.48, P=0.002) and a higher risk of death (HR=2.03, P=0.020). Conclusion: For patients with advanced SNM, the efficacy of endoscopic surgery can be comparable to that of open surgery when presence of safe surgical margins, and a treatment plan based on transnasal endoscopic surgery as the main comprehensive treatment is recommended.

[Cost-effectiveness of endoscopic nasopharyngectomy in locally recurrent rT1-rT3 nasopharyngeal carcinoma: a study based on Markov model].

Objective: To perform a cost-effectiveness analysis of endoscopic surgery versus intensity-modulated radiotherapy in the treatment of locally recurrent nasopharyngeal carcinoma (rNPC) from a health-economic perspective. Methods: From September 30, 2011 to January 16, 2017, a total of 200 patients were enrolled in the First Affiliated Hospital of Sun Yat-sen University, the First People's Hospital of Foshan, and Sun Yat-sen University Cancer Center. These patients were diagnosed as locally rT1-rT3 stage rNPC and were randomly assigned 1︰1 to the endoscopic surgery group (ENPG) and the intensity-modulated radiotherapy group (IMRT). There were 69 males and 31 females in ENPG, aging from 38 to 55 years. There were 72 males and 28 females in IMRT aging from 41 to 54 years. A retrospective cost-effectiveness analysis of the cohort was conducted using a Markov model. For each modality, data on survival and quality-adjusted life year (QALY) were sourced from relevant articles, and cost prices were included regarding treatment. Weibull distribution was used to estimate time-dependent transition probability. Beta-regression was used to convert the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) to utility. Results: The total cost of ENPG was 29 611.88 yuan, and the total cost of IMRT was 110 082.51 yuan. The incremental cost-effectiveness ratio (ICER) of ENPG versus radiotherapy for locally rNPC was -85 555.88 yuan/QALY, which was less than 3 times of Chinese gross domestic product (GDP) per capita. Sensitivity analysis showed that the cost of IMRT had the greatest impact on ICER. ICER was stable within 10% fluctuation of all the parameters. Conclusion: It is economical cost-effective to treat locally rNPC with ENGP versus IMRT.

[Study on the relationship between urinary polycyclic aromatic hydrocarbons metabolites and pulmonary function in community population].

Objective: To investigate the relationship between urinary polycyclic aromatic hydrocarbons(PAHs) metabolites and pulmonary function in community population. Methods: A total of 4 812 participants were recruited from two communities in Wuhan city from April to May 2011 and two communities in Zhuhai city in May 2012. Information of demographic characteristics and life style was collected by semi-structural questionnaire. Physical examination was performed and pulmonary function was measured. Morning urine was also collected. The concentration of 12 urinary PAHs metabolites was tested and classified into four types by chemical structure, including hydroxynaphthalene, hydroxyfluorene, hydroxyphenanthrene and hydroxypyrene. The level of pulmonary function in different group of urinary PAHs metabolites was compared by using covariance analysis. The association of the urinary PAHs metabolites and pulmonary function was analyzed by using generalized linear model, and the interaction of different population characteristics and life style on the association was analyzed. Results: The age of participants was(51.99±13.64) years old, and 67.66% (n=2 565) of the population were women. The M (P(25), P(75)) of concentration of total urinary PAHs metabolites was 5.72 (3.91,8.72) µg/mmol Cr. After controlling for variables including age, gender, city, Waist-to-Hip Ratio, smoking status, drinking situation, physical activity, cooking meals at home or not, kitchen ventilation and exposure to dust as confounding factors, generalized linear model showed that each 1-unit increase in log-transformed levels of hydroxynaphthalene, hydroxyfluorene, hydroxyphenanthrene, hydroxypyrene and total PAHs was associated with 26.83 (95%CI: -48.18, -5.48) , 21.86 (95%CI: -40.49, -3.23), 26.18(95%CI: -48.27, -4.09), 34.95 (95%CI: -55.95, -13.94), and 35.23 (95%CI: -58.93, -11.54) ml reduction of FVC and 29.36 (95%CI: -47.23, -11.48), 20.79 (95%CI: -36.39, -5.19), 22.65 (95%CI: -41.15, -4.15), 31.44(95%CI: -49.03, -13.85), and 33.20 (95%CI: -53.04, -13.36) ml reduction of FEV(1) respectively (all P values<0.05). Compared to non-alcohol users and participants with home cooking, the association was more evident in alcohol users and participants without home cooking(P for interaction<0.05). Conclusion: The exposure to PAHs was associated with decreased pulmonary function, and the association was more evident in alcohol users and participants without home cooking.

MicroRNA-421 promotes inflammatory response of fibroblast-like synoviocytes in rheumatoid arthritis by targeting SPRY1.

OBJECTIVE: The aim of this study was to investigate whether microRNA-421 could participate in the proliferative, migratory and inflammatory changes of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis by targeting SPRY1. PATIENTS AND METHODS: The expressions of microRNA-421 and SPRY1 in synovial tissues and FLS were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot, respectively. The binding condition between microRNA-421 and SPRY1 was verified by the Dual-Luciferase reporter gene assay. MicroRNA-421 mimics and inhibitor were constructed and transfected. The levels of extracellular interleukin-1 (IL-1), IL-6, and COX2 in FLS after microRNA-421 mimics or inhibitor transfection were detected by enzyme-linked immunosorbent assay (ELISA). The regulatory effect of microRNA-421 on the proliferation and migration of FLS was detected using cell counting kit-8 (CCK-8) and transwell assay, respectively. Furthermore, collagen-induced RA mouse model was constructed to confirm the specific effect of microRNA-421 on regulating RA development. RESULTS: MicroRNA-421 was highly expressed in the synovial tissues of RA patients. SPRY1 expression in FLS was negatively regulated by microRNA-421. Moreover, the overexpression of microRNA-421 significantly promoted proliferative, invasive potentials and inflammatory response of FLS. In vivo, RA mouse model indicated that downregulated microRNA-421 and upregulated SPRY1 were observed in mice injected with cortisone and microRNA-421 inhibitor when compared with those of controls. CONCLUSIONS: MicroRNA-421 promotes the inflammatory response of fibroblast-like synoviocytes in rheumatoid arthritis by downregulating the SPRY1 expression.

[Lateral endoscopic transorbital approach to middle skull base: anatomical and surgical practice study].

Objective: To investigate the anatomical and surgical approaches to middle cranial fossa through orbital lateral wall under endoscope. Methods: Cadaveric formalin fixed specimens and fresh colored silicone injected specimens were used for this study. All anatomic technical measurements were performed under 0° and 30° endoscope and infrared rays navigation. The surgical approach was designed with the bony opening on the lateral wall of orbit through which the lateral side of the middle cranial fossa could be directly entered under endoscope. One case of recurrent meningioma was performed through this surgical approach. SPSS 20.0 software was used for statistical analysis. Results: The approach can directly enter the middle cranial fossa and expose anatomic landmarks including superior orbital fissure, lateral side of cavernous sinus, foramen rotundum, foramen ovale, foramen spinosum, petrosal bone and others as well as Ⅱ, Ⅲ, Ⅳ, Ⅴ, Ⅵ cranial nerves under endoscope. The maximal bony opening through the lateral wall of orbit was measured, with a horizontal diameter of (1.38±0.68) cm, a vertical diameter of (2.02±0.32) cm, a depth of (1.44±0.42) cm from bony opening margin to the dura. The recurrent meningioma involving lateral side of the middle skull base was successfully removed by this surgical approach through lateral wall of orbit. Conclusion: Lateral transorbital endoscopic approach to the lateral side of middle skull base is a safe, feasible, and minimally invasive method, which allows surgeons to directly manipulate diseases involving this area with good visualization and minimal invasion under endoscope.

[Correlation between prognosis and IL-33 expression in head and neck squamous cell carcinoma].

Objective:To determine the correlation between the expression of IL-33 and significance in cancer biologial and patient's prognosis in head and neck squamous cell carcinoma (HNSCC). Method:Twenty pairs of tumor tissue and adjacent normal tissue were collected. qRT-PCR and immunohistochemistry (IHC) were used to detect the expression of IL-33 mRNA and protein in tissues. Correlation between IL-33 expression with clinicopathologic features of 107 HNSCC patients were analyzed. Result:IL-33 mRNA and protein expression levels in normal tissue were higher than paired tumor tissue. IL-33 level was significantly lower in patients with advanced T stages, lymph node metastases and advanced clinical stages, IL-33 expression was higher in well differentiated tumor than moderate or poor differentiated tumor. Low IL-33 expression predicts poor prognosis. Multivariate analysis indicated that IL-33 expression was an independent predictive factor. Conclusion:IL-33 is related with the clinicopathological features in HNSCC and could be an independent predictor of HNSCC prognosis.

[Clinical application of supraclavicular flap for oncologic reconstruction of hypopharynx and upper esophagus].

Objective: To assess the efficacy of supraclavicular artery island flap (SCAIF) for the reconstruction of hypopharynx and upper esophagus. Methods: The SCAIF procedure on was used in 10 patients, including 8 with hypopharygeal carcinomas, 1 with esophageal carcinoma and neck skin invasion and 1 with hypopharyngeal leiomyosarcoma, at the Otorhinolaryngology Hospital, the First Affiliated Hospital, Sun Yatsen University between December 2015 and June 2017. The sizes of the flaps were measured in (4-8) cm×(5-12) cm. Clinical indexes such as harvesting time and survival were recorded. Results: Harvesting time for SCAIF ranged from 20 to 30 minutes, averaging 26 minutes. Nine flaps survived, one flap had partially necrosis. Functional outcomes were excellent and the donor sites were direct closed without complications. Conclusions: SCAIF is a versatile, reliable, and easily harvested flap, with good cosmetic and functional outcomes for reconstructing the defects of hypopharynx and upper esophagus.

Risk of tuberculosis comparison in new users of antitumour necrosis factor-α and with existing disease-modifying antirheumatic drug therapy.

WHAT IS KNOWN AND OBJECTIVE: Patients with rheumatic disease are at risk for infections. Evaluating antitumour necrosis factor (anti-TNF) drug-associated risk of infections requires justification of baseline risk in the population at high risk of infection. We examined the incidence of active tuberculosis (TB) and its risk factors in patients with rheumatic disease started with anti-TNF-α therapy or with existing disease-modifying antirheumatic drug (DMARD) therapy. METHODS: A retrospective cohort study of anti-TNF-α therapy new users (anti-TNF-α group) and those starting with a DMARD after the failure of at least one other DMARD or who had added to existing DMARD treatment (DMARD group) for rheumatic disease in the largest medical setting in Taiwan from 1 January 2005 through 31 November 2013 was conducted to determine relative risk of TB between patient groups. Patients in the DMARD group were stratified into "mild" and "severe" disease severity as proxies for low and high background risk of infection. RESULTS AND DISCUSSION: A total of 3640 patients were enrolled (anti-TNF: 955; DMARD: 2685). The incidence of TB was 903.9/100 000 patient-years for anti-TNF-α new users and 391.7/100 000 patient-years for DMARD switchers. In Cox regression model, adjusted HR for TB in the anti-TNF-α group was higher than for the entire DMARD group (aHR, 2.41; 95% confidence interval [CI], 1.2-4.85), subgroup with mild disease (2.91; 1.31-6.47) and subgroup with severe disease (1.65; 0.68-4.03). Significant independent risk factors for TB were being male, age ≥60 years, history of respiratory disease, glucocorticoids dose >7.5 mg/d and living in a TB-prevalent region. WHAT IS NEW AND CONCLUSION: Anti-TNF-α therapy was independently associated with increased risk of TB in patients with mild disease, but it was not significantly correlated in patients with severe disease after adjusting for confounders.

Misdiagnosed paranasal gossypiboma: a 10-year experience with 21 cases at a tertiary center.

BACKGROUND: Different from rhinoliths, the paranasal gossypiboma is a foreign body, such as a surgical sponge, left in the nasal cavity. It is a rare, frequently misdiagnosed disease that has rarely been reported. We summarize its clinical characteristics, management, and possible risk factors. METHODOLOGY: We reviewed medical records of confirmed paranasal gossypibomas at a tertiary medical center between 2005 and 2015. Clinical symptoms, age, sex, anatomic sites, endoscopic photography, computed tomography, intraoperative findings, and past medical history were reviewed. RESULTS: The study included 21 patients, each of whom had ultimately undergone two operations. Among them, 20 underwent endoscopic nasal surgery in primary hospitals, and 15 had been misdiagnosed during the second surgery. The average interval to discovery of a retained foreign body was 200 days. Predominant occurrence sites were the maxillary and ethmoid sinuses. Computed tomography showed paranasal gossypiboma as a heterogeneous cystic lesion with a thin calcified shell. CONCLUSIONS: A history of endoscopic nasal surgery, especially performed at a primary hospital, is a warning sign for clinicians. Computed tomography can add to the warning by showing a heterogeneous cystic lesion with a thin calcified shell. Clinicians should be aware of these characteristics to avoid misdiagnosing paranasal gossypiboma.

[Therapy of adult-onset laryngeal papilloma: integrallty submucosal dissection of the tumor by CO2 laser].

Objective: To evaluate the feasibility and efficacy of the integrallty submucosal resection of adult-onset laryngeal papilloma by CO2 laser. Methods: A group of 64 cases (36 males and 28 females, multipe lesions 54 cases and single lesion 10 cases, aged 18-75 years, mean age 43.13 years) with adult-onset laryngeal papilloma encountered in the first affliated hospital of Sun Yatsen university from 2009 to 2015 was retrospectively analyzed. All cases were treated with integrallty submucosal dissection of the tumor by CO2 laser, and observed the changes of tumor integral scope, inter-operative, operative processes, postoperative voice quality, postoperative scarring, and the tracheotomy conditions, which were analysed and evaluated. Results: A total of 64 patients were followed up from 1 year to 5 years. Preoperative tumor integral scope of these patients averaged of 7.00. A total of 62 cases kept 0 score of the tumor integral scope for at least one year, which lead to a clinical cure rate of 96.9%. The inter-operative averaged of 25.7 months. The total operative processes of these patients were 87 times (mean time 1.36). Four cases resulted in postoperative scarring. However these was a good result in postoperative voice quality with a mean score 4.25. As to the changes of tumor integral scope, all cases got a declining score (mean score 6.72), which resulted in a remission rate of 100%. Conclusion: The integrallty submucosal dissection of adult-onset 1aryngeal papilloma by CO2 laser was an effective way to reduce the tumor integral scope; lengthen their inter-operative; decrease the operative processes, avoid the occurrence of tracheotomy; and improve the postoperative voice quality. Most of the patients could even be cured ultimately.

Large recovery strain in Fe-Mn-Si-based shape memory steels obtained by engineering annealing twin boundaries.

Shape memory alloys are a unique class of materials that can recover their original shape upon heating after a large deformation. Ti-Ni alloys with a large recovery strain are expensive, while low-cost conventional processed Fe-Mn-Si-based steels suffer from a low recovery strain (<3%). Here we show that the low recovery strain results from interactions between stress-induced martensite and a high density of annealing twin boundaries. Reducing the density of twin boundaries is thus a critical factor for obtaining a large recovery strain in these steels. By significantly suppressing the formation of twin boundaries, we attain a tensile recovery strain of 7.6% in an annealed cast polycrystalline Fe-20.2Mn-5.6Si-8.9Cr-5.0Ni steel (weight%). Further attractiveness of this material lies in its low-cost alloying components and simple synthesis-processing cycle consisting only of casting plus annealing. This enables these steels to be used at a large scale as structural materials with advanced functional properties.

A pharmacokinetic model for predicting absorption, elimination, and tissue burden of toxaphene in rats.

A two-compartment pharmacokinetic model was formulated to predict absorption, elimination, and tissue burden of toxaphene in rats. The model was constructed based on the database of Crowder and Dindal (Bull. Environ. Contam. Toxicol. 12, 320-327, 1974) and included six tissue compartments: blood, brain, liver, muscle, fat, and carcass. The pharmacokinetically based dosimetry indicated that absorption of toxaphene was fast in fat, whole body, carcass, and blood, relatively slow in liver and muscle, and slow in brain. In contrast, the elimination rate was rapid in whole body, muscle, and blood, moderate in carcass and brain, and slow in liver and fat. Tissue burden was highest in fat, whole body, and blood, intermediate in liver, and lowest in brain. The model performance was evaluated by the data set of Pollock and Hillstrand (J. Environ. Sci. Health B 17, 635-648, 1982) on toxaphene absorption and elimination in pregnant rats. Validity of the model was confirmed by the close agreement between the predicted and observed tissue burdens of toxaphene in target tissues. Disposition of toxaphene via feces was a dominant excretory pathway while urinary excretion was a minor elimination route in male rats. However, for pregnant rats, excretion of toxaphene both in urine and feces were of similar magnitude. These characteristics of elimination are valuable for understanding the metabolism of toxaphene in pregnant rats. The model serves as a starting point for a quantitative, mechanism-based understanding of the processes that influence the pharmacokinetics of toxaphene in mammalian systems.

The role of conjugation in hepatotoxicity of troglitazone in human and porcine hepatocyte cultures.

In primary human and porcine hepatocyte cultures, we investigated the relationship between metabolism and cytotoxicity of troglitazone. Treatment of human hepatocytes for 2 h with 10, 20, 25, 35, and 50 microM troglitazone in protein-free medium resulted in concentration-dependent decreases in total protein synthesis. Decreases at 10 and 20 microM were reversible by 24 h, however protein synthesis did not recover at concentrations >/=25 microM. Troglitazone at 50 microM caused cellular death. In porcine hepatocytes, 100 microM troglitazone was lethal, whereas at 50 microM, protein synthesis completely recovered by 24 h. Recovery in protein synthesis was associated with metabolism of parent drug, whereas toxicity correlated (r(2) = 0.82) with accumulation of unmetabolized troglitazone. By 1 h, in human hepatocytes, troglitazone was metabolized to similar amounts of sulfate and quinone metabolites with little glucuronide detected. In contrast, porcine hepatocytes metabolized troglitazone to the similar amounts of glucuronide and the quinone metabolites with little sulfate detected. Exposure of human hepatocytes to a combination of 10 microM troglitazone and 10 microM 2,4-dichloro-4-nitrophenol resulted in a 70% decrease in protein synthesis, associated with 90% inhibition in the formation of troglitazone sulfate, a 4-fold increase in unmetabolized troglitazone, and no effect on formation of the quinone metabolite. Treatment with a combination of acetaminophen or phenobarbital with 20 microM troglitazone resulted in sustained decrease in protein synthesis associated with inhibition of sulfation and accumulation of troglitazone. These results suggest that inhibition of troglitazone sulfation may result in increased hepatotoxicity due to exposure to parent drug, or increased metabolism by alternate pathways.

Trace analysis of acetaldehyde as fluorogenic derivative by high performance liquid chromatography.

A sensitive method is described for the determination of acetaldehyde as a fluorogenic derivative of decahydroacridin-1,8-dione by high performance liquid chromatography. The analytical derivatization is based on the reaction of acetaldehyde in an acidic aqueous system with 1,3-cyclohexanedione and ammonium acetate. The resulting derivative was separated by a reversed-phase C-18 column and monitored with a fluorescent detector (lambda ex, 375nm; lambda em, 512nm). Several parameters affecting the derivatization of acetaldehyde were studied. The linear range of the method for the quantitation of acetaldehyde was between 20 and 800 pmol in aqueous sample (0.5 mL). Application of the method to the analysis of acetaldehyde in plasma was performed.

[Coetsoidin A, a new diterpenoid from Rabdosia coetsoides C. Y. Wu].

From the leaves of Rabdosia coetsoides C. Y. Wu, a new diterpenoid, coetsoidin A (I) was isolated and its structure was established by spectroscopic and X-ray diffraction analysis. It is the first instance of a kaurene type diterpenoid possessing alpha,beta-unsaturated ketone functionality in ring B.