Numerical and experimental evaluation of nasopharyngeal aerosol administration methods in children with adenoid hypertrophy.

Administering aerosol drugs through the nasal pathway is a common early treatment for children with adenoid hypertrophy (AH). To enhance therapeutic efficacy, a deeper understanding of nasal drug delivery in the nasopharynx is essential. This study uses an integrated experimental, numerical modelling approach to investigate the delivery process of both the aerosol mask delivery system (MDS) and the bi-directional delivery system (BDS) in the pediatric nasal airway with AH. The combined effect of respiratory flow rates and particle size on delivery efficiency was systematically analyzed. The results showed that the nasopharyngeal peak deposition efficiency (DE) for BDS was approximately 2.25-3.73 times higher than that for MDS under low-flow, resting and high-flow respiratory conditions. Overall nasopharyngeal DEs for MDS were at a low level of below 16 %. For each respiratory flow rate, the BDS tended to achieve higher peak DEs (36.36 % vs 9.74 %, 37.80 % vs 14.01 %, 34.58 % vs 15.35 %) at smaller particle sizes (15 µm vs 17 µm, 10 µm vs 14 µm, 6 µm vs 9 µm). An optimal particle size exists for each respiratory flow rate, maximizing the drug delivery efficiency to the nasopharynx. The BDS is more effective in delivering drug aerosols to the nasal cavity and nasopharynx, which is crucial for early intervention in children with AH.

Numerical investigation of nanoparticle deposition in the olfactory region among pediatric nasal airways with adenoid hypertrophy.

To understand inhaled nanoparticle transport and deposition characteristics in pediatric nasal airways with adenoid hypertrophy (AH), with a specific emphasis on the olfactory region, virtual nanoparticle inhalation studies were conducted on anatomically accurate child nasal airway models. The computational fluid-particle dynamics (CFPD) method was employed, and numerical simulations were performed to compare the airflow and nanoparticle deposition patterns between nasal airways with nasopharyngeal obstruction before adenoidectomy and healthy nasal airways after virtual adenoidectomy. The influence of different inhalation rates and exhalation phase on olfactory regional nanoparticle deposition features was systematically analyzed. We found that nasopharyngeal obstruction resulted in significant uneven airflow distribution in the nasal cavity. The deposited nanoparticles were concentrated in the middle meatus, septum, inferior meatus and nasal vestibule. The deposition efficiency (DE) in the olfactory region decreases with increasing nanoparticle size (1-10 nm) during inhalation. After adenoidectomy, the pediatric olfactory region DE increased significantly while nasopharynx DE dramatically decreased. When the inhalation rate decreased, the deposition pattern in the olfactory region significantly altered, exhibiting an initial rise followed by a subsequent decline, reaching peak deposition at 2 nm. During exhalation, the pediatric olfactory region DE was substantially lower than during inhalation, and the olfactory region DE in the pre-operative models were found to be significantly higher than that of the post-operative models. In conclusions, ventilation and particle deposition in the olfactory region were significantly improved in post-operative models. Inhalation rate and exhalation process can significantly affect nanoparticle deposition in the olfactory region.

[Effect of nasal swell body on nasal airflow and Artemisia pollen deposition].

Objective:The nasal swell body（NSB） consists of the nasal septal cartilage, nasal bone, and swollen soft tissue, all of which are visible during endoscopic and imaging examinations. Although the function of the NSB remains uncertain, there is evidence to suggest that it plays a vital role in regulating nasal airflow and filtering inhaled air. Based on anatomical and histological evidence, it is hypothesized that the NSB is indispensable in these processes. This study aims to investigate the impact of NSB on nasal aerodynamics and the deposition of allergen particles under physiological conditions. Methods:The three-dimensional （3D） nasal models were reconstructed from computed tomography （CT） scans of the paranasal sinus and nasal cavity in 30 healthy adult volunteers from Northwest China, providing basis for the construction of models without NSB following virtual NSB-removal surgery. To analyze the distribution of airflow in the nasal cavity, nasal resistance, heating and humidification efficiency, and pollen particle deposition rate at various anatomical sites, we employed the computed fluid dynamics（CFD） method for numerical simulation and quantitative analysis. In addition, we created fully transparent segmented nasal cavity models through 3D printing, which were used to conduct bionic experiments to measure nasal resistance and allergen particle deposition. Results:①The average width and length of the NSB in healthy adults in Northwest China were （12.85±1.74） mm and （28.30±1.92） mm, respectively. ②After NSB removal, there was no significant change in total nasal resistance, and cross-sectional airflow velocity remained essentially unaltered except for a decrease in topical airflow velocity in the NSB plane. ③There was no discernible difference in the nasal heating and humidification function following the removal of the NSB; ④After NSB removal, the deposition fraction（DF） of Artemisia pollen in the nasal septum decreased, and the DFs post-and pre-NSB removal were（22.79±6.61）% vs （30.70±12.27）%, respectively; the DF in the lower airway increased, and the DFs post-and pre-NSB removal were（24.12±6.59）% vs （17.00±5.57）%, respectively. Conclusion:This study is the first to explore the effects of NSB on nasal airflow, heating and humidification, and allergen particle deposition in a healthy population. After NSB removal from the healthy nasal cavities: ①nasal airflow distribution was mildly altered while nasal resistance showed no significantly changed; ②nasal heating and humidification were not significantly changed; ③the nasal septum's ability to filter out Artemisia pollen was diminished, which could lead to increased deposition of Artemisia pollen in the lower airway.

Effect of different degrees of adenoid hypertrophy on pediatric upper airway aerodynamics: a computational fluid dynamics study.

To improve the diagnostic accuracy of adenoid hypertrophy (AH) in children and prevent further complications in time, it is important to study and quantify the effects of different degrees of AH on pediatric upper airway (UA) aerodynamics. In this study, based on computed tomography (CT) scans of a child with AH, UA models with different degrees of obstruction (adenoidal-nasopharyngeal (AN) ratio of 0.9, 0.8, 0.7, and 0.6) and no obstruction (AN ratio of 0.5) were constructed through virtual surgery to quantitatively analyze the aerodynamic characteristics of UA with different degrees of obstruction in terms of the peak velocity, pressure drop (△P), and maximum wall shear stress (WSS). We found that two obvious whirlpools are formed in the anterior upper part of the pediatric nasal cavity and in the oropharynx, which is caused by the sudden increase in the nasal cross-section area, resulting in local flow separation and counterflow. In addition, when the AN ratio was ≥ 0.7, the airflow velocity peaked at the protruding area in the nasopharynx, with an increase 1.1-2.7 times greater than that in the nasal valve area; the △P in the nasopharynx was significantly increased, with an increase 1.1-6.8 times greater than that in the nasal cavity; and the maximum WSS of the posterior wall of the nasopharynx was 1.1-4.4 times larger than that of the nasal cavity. The results showed that the size of the adenoid plays an important role in the patency of the pediatric UA.

Melatonin reduces IL-33 and TSLP expression in human nasal epithelial cells by scavenging ROS directly.

BACKGROUND: Chronic rhinosinusitis (CRS) is a chronic mucosal inflammation of the nasal cavity and sinuses. It is classified into CRS without nasal polyps and CRS with nasal polyps (CRSwNP). CRSwNP has high recurrence, especially CRSwNP with massive eosinophil infiltration which is mediated by type 2 inflammatory response. Melatonin is a hormone secreted by the pineal gland, it has powerful antioxidant and anti-inflammatory effects in addition to regulating biological rhythms. There are no studies on melatonin for the treatment of CRS, so we aimed to explore whether melatonin could be used for the treatment of CRS. MATERIALS AND METHODS: In this study, we used melatonin to treat a cell model of CRS. Subsequently, MTT assay was performed to examine the cell viability of human nasal epithelial cells (HNEpCs), a reactive oxygen species (ROS) kit to detect ROS production, a malondialdehyde (MDA) kit to detect the MDA content in the cell culture supernatant, and an apoptosis kit and Western blot analysis to detect apoptosis. The expressions of Nrf2, HO-1, IL-33, TSLP, and IL-25 were detected by Western blot analysis. RESULTS: Melatonin improved the viability of HNEpCs, reduced lipopolysaccharide-induced ROS, reduced the MDA content, and inhibited their apoptosis. More importantly, melatonin reduced the expression of IL-33 and TSLP, an important phenomenon for the treatment of CRSwNP. CONCLUSION: Melatonin protects HNEpCs from damage in inflammation and reduces IL-33 and TSLP expression of HNEpCs.

HO-1: a new marker for predicting postoperative recurrence of CRSwNP.

BACKGROUND: Chronic rhinosinusitis with polyps (CRSwNP) is a subtype of chronic rhinosinusitis and is highly prone to recurrence; therefore, it is urgent to find appropriate markers to predict recurrence of CRSwNP after surgery. PURPOSE: We aim to investigate the expression of HO-1 in CRSwNP and assess its value of predicting postoperative recurrence of CRSwNP. METHODS: We recruited 77 participants and collected clinical data of all. We use Immunohistochemical staining to determine the expression of HO-1 in tissues. We use Spearman correlation test to analyze the correlation between HO-1 positive cell count and clinical score, and ROC curve to assess the value of HO-1 positive cell count in predicting recurrence of CRSwNP. RESULTS: HO-1 positive cells were macrophages and significantly increased in CRSwNP; HO-1 positive cell count was negatively correlated with preoperative SNOT-22 score; HO-1 can predict postoperative recurrence of CRSwNP, AUC = 0.80, p = 0.004. CONCLUSION: HO-1 is a biochemical marker of CRSwNP and can predict postoperative recurrence of CRSwNP.

Evaluation of nasal function after endoscopic endonasal surgery for pituitary adenoma: a computational fluid dynamics study.

OBJECTIVE: To analyze the effect of different endoscopic endonasal approaches (EEAs) on nasal airflow and heating and humidification in patients with pituitary adenoma (PA) by computational fluid dynamics (CFD). METHODS: A three-dimensional pre-surgical model (Pre) of the nasal cavity and 6 that were post-EEA surgery were created from computed tomography scans as follows: small posterior septectomy (0.5 cm, sPS), middle posterior septectomy (1.5 cm, mPS), large posterior septectomy (2.5 cm, lPS), and sPS with middle turbinate resection (sPS-MTR), mPS-MTR, and lPS-MTR. Simulations were performed by CFD to compare the changes in different models. RESULTS: The temperature in the nasal vestibule rose more rapidly than in other parts of the nasal cavities in all models. There were no apparent differences in temperature and humidity among the models in sections anterior to the middle turbinate head (C6 section). MTR significantly influenced airflow distribution between the bilateral nasal cavities and the different parts of the nasal cavity, while changes in temperature and humidity in each section were mainly affected by MTR. The temperature and humidity of the choana and nasopharynx of each postoperative model were significantly different from those of the preoperative model and the change in values significantly correlated with the surface-to-volume ratio (SVR) of the airway. CONCLUSIONS: Changes due to the different nasal structures caused different effects on nasal function following the use of EEA surgery for the treatment of PA. CFD provided a new approach to assess nasal function, promising to provide patients with individualized preoperative functional assessment and surgical planning.

[Study on changes of nasal resistance based on 3D printing transparent nasal cavity models].

Objective:To investigate the causal relationship between the minimum cross-sectional area of nasal cavity and nasal resistance. Methods:Thirty transparent detachable 3D printing nasal cavity models were made. The airway was completely blocked with sealing material at different anatomical sections. Then ventilatable nasal drainage tubes with different cross-sectional areas were used to pass through the nasal cavity. Nasal resistance was measured. SPSS was used for statistical analysis. Results:①The postoperative nasal resistances of patients and 3D printing nasal cavity models were （0.38±0.15）Pa· s/mL and （0.39±0.02）Pa· s/mL respectively. There was no statistical difference between the two groups.The preoperative nasal resistance of patients was （0.56±0.09）Pa· s/mL, and the postoperative nasal resistance of the models was significantly descreased by 31% compared with preoperative nasal resistance of the patients, with statistically significant difference（P<0.05）. ②When the ventilatable nasal drainage tubes with a cross-sectional area of 3.14 square millimeters was located in the the upper part of common meatus and the nasal valve area, the nasal cavity is moderately blocked, and the nasal resistances were （1.80±0.30） times and （2.02±0.36） times of that before the obstruction respectively. When the ventilatable nasal drainage tube was located in the lower part of common meatus,the nasal resistance was （1.68±0.28） times of that before the obstruction. ③When the ventilatable nasal drainage tubes with a cross-sectional area of 6.28 square millimeters and were located in the lower part of common meatus, the upper part of common meatus and nasal valve area, the nasal resistances were （1.44±0.23） times, （1.50±0.25） times and （1.60±0.27） times of those before obstruction, respectively. ④When the ventilatable nasal drainage tubes with a cross-sectional area of 9.42 square millimeters were located in the above areas, nasal ventilation was nearly normal without obvious nasal obstruction. The nasal resistances were （1.17±0.18） times, （1.26±0.21） times and （1.33±0.24） times of those before obstruction, respectively. ⑤The nasal resistance was statistically significant correlated with the cross-sectional area of the ventilation tubes and the obstruction sites. The correlation coefficients were -0.895 and 0.339, respectively （P<0.05）. Conclusion:①3D printing can quickly and accurately replicate anatomical structure of the nasal cavity, and can be used as a research method for quantifitative measurement of nasal resistance. ②The minimum cross-sectional area of nasal cavitiy is the main determinant of nasal resistance. ③The obstruction site is the secondary determinant of nasal resistance. When the degree of nasal obstruction is the same , the nasal resistance in the nasal valve area is sightly higher than that in the common meatus.

Impact of the Extent of Surgical Resection on Patients With Intradural Extramedullary Bronchogenic Cysts: A Retrospective Institutional Experience and Review of the Literature.

Intradural extramedullary bronchogenic cysts (IEBC) are rare congenital cystic lesions. The clinical manifestations, radiological characteristics, especially the optimal treatment regimen are not well-understood. We retrospectively analyzed a series of patients with confirmed IEBC in Tangdu hospital and reviewed the published works to gain a comprehensive understanding of IEBC. In our institution, nine consecutive patients had pathologically confirmed IEBC between 2005 and 2018. We also identified 27 patients from previous studies. The most common presentations on magnetic resonance imaging (MRI) were hypointensity on T1-weighted images (T1WI), hyperintensity on T2-weighted images(T2WI), and no improvement on T1WI contrast-enhanced with gadolinium (94.4%). All patients in our center and the patients we reviewed received surgical resection; gross total resection (GTR) and partial resection (PR) were achieved in 20 (55.6%) and 16 (44.4%) patients, respectively. The symptom remission rate of patients who underwent GTR was 100%, which was similar to those who underwent PR (93.8%) (P = 0.457). The recurrence rate was 12.5% in the group who underwent PR and nil after GTR (P = 0.202). According to our current investigation, the surgical resection degree is irrelevant to the symptom remission rate. Therefore, we suggest that total resection should not be recommended for cases with tight adhesion. For patients with PR, longer follow-up will be necessary to determine the long-term outcome.

Numerical Simulation of Nasal Airflow Aerodynamics, and Warming and Humidification in Models of Clival Chordoma Pre and Post-Endoscopic Endonasal Surgery.

OBJECTIVES: To study the effect of endoscopic endonasal surgery on nasal function for the treatment of clival chordoma. METHODS: Pre and post-operative computed tomography (CT) scans of a case of chordoma treated with an endoscopic endonasal approach (EEA) were collected retrospectively, and models of the nasal cavity were reconstructed so that a subsequent numerical simulation of nasal airflow characteristics, warming, and humidification could be conducted. RESULTS: Middle turbinectomy resulted in redistribution of airflow within the nasal cavity, and the most significant changes occurred in the middle section. Consistent with the results of airflow evaluation, it was found that the change in nasal anatomical structure significantly reduced warming and humidification. Nasal humidification decreased substantially when postoperative loss of mucosa was taken into consideration. The H2O mass fraction of pharynx in inspiration phase were significantly correlated with airway surface-to-volume ratio (SVR). CONCLUSIONS: The EEA for chordoma significantly affected nasal function. Attention should be paid to the protection of nasal structure and the associated mucosa.

Prognostic and Predictive Factors in Elderly Patients With Glioblastoma: A Single-Center Retrospective Study.

Glioblastoma (GBM) is the most common primary malignant intracranial tumor and the median age at diagnosis is 65 years. However, elderly patients are usually excluded from clinical studies and age is considered as an independent negative prognostic factor for patients with GBM. Therefore, the best treatment method for GBM in elderly patients has remained controversial. Elderly GBM patients (≥ 60 years old) treated between January 2015 and December 2019 were enrolled in this study. Medical records were reviewed retrospectively, and clinicopathological characteristics, treatments, and outcomes were analyzed. A total of 68 patients were included, with a median age of 65.5 years (range: 60-79). The median preoperative Karnofsky performance scale (KPS) score was 90 (range 40-100) and median postoperative KPS score was 80 (range 0-90). Univariate analysis results showed that age, gender, comorbidities, preoperative KPS < 90 and MGMT promoter methylation were not significantly associated with PFS and OS. On the other hand, total resection, postoperative KPS ≥ 80, Ki67 > 25%, and Stupp-protocol treatment were significantly associated with prolonged PFS and OS. Moreover, multivariate analysis found that postoperative KPS ≥ 80, total resection, and Stupp-protocol treatment were prognostic factors for PFS and OS. The findings of this study have suggested that, on the premise of protecting function as much as possible, the more aggressive treatment regimens may prolong survival for elderly patients with GBM. However, further studies, particularly prospective randomized clinical trials, should be conducted to provide more definitive data on the appropriate management of elderly patients, especially for patients with MGMT promoter methylation.

Resource Value Discovery and Utilization of Wastes in Industrialization of Rhei Radix et Rhizoma / 中国实验方剂学杂志

The recycling of traditional Chinese medicine （TCM） wastes is an important research topic to be solved urgently in the industrialization of TCM resources. Rhei Radix et Rhizoma is a bulk Chinese herb mainly derived from Rheum palmatum，R. tanguticum，and R. officinale. At present，these three medicinal plants have been cultivated on a large scale and widely used in the fields of medicine，health care，food，cosmetics，and veterinary medicine，with an annual demand of more than 5 500 tons（1 ton=1 000 kg）. However，a large number of wastes such as non-medicinal parts and residues produced in the production and deep processing are discarded because there is no effective way of utilization，resulting in serious waste of resources and environmental pollution. The non-medicinal parts contain not only the chemical components and pharmacological effects similar to those of roots and rhizomes but also a variety of amino acids，mineral elements，and conventional nutrients. They have a long history of use，and the content of some resource components is higher than that in roots and rhizomes. In particular，their stems and leaves exhibit great potential to be consumed as food and medicine due to high safety. Besides，the content of anthraquinones in Rhei Radix et Rhizoma residue is high and it possesses good antibacterial activity. It can be seen that the waste from the industrialization of Rhei Radix et Rhizoma has high utilization value. Hence，based on the relevant literature and investigation on the application of producing areas in China and abroad，the paper summarized the utilization status of their medicinal and non-medicinal parts，the waste production in the industrialization，as well as the active substances and utilization ways and put forward the multi-level and multi-path utilization strategy of Rhei Radix et Rhizoma wastes，in order to provide reference for the rational development and application of Rhei Radix et Rhizoma resources and promote the effective utilization and green development of the corresponding wastes.

Clinical Features and Molecular Markers on Diffuse Midline Gliomas With H3K27M Mutations: A 43 Cases Retrospective Cohort Study.

PURPOSE: Diffuse midline gliomas (DMG) with H3K27M mutations have been identified as a rare distinctive entity with unique genetic features, varied molecular alterations, and poor prognosis. The current study aimed to evaluate the clinical characteristics and profile of molecular markers on patients with a DMG harboring H3K27M mutations, and explore the impact of this genetic makeup on overall survival. METHODS: We retrospectively analyzed 43 consecutive patients diagnosed with a DMG harboring H3K27M mutations (age range 3 to 75 years) and treated in a tertiary institution within China between January 2017 to December 2019. Various clinical and molecular factors were evaluated to assess their prognostic value in this unique patient cohort. RESULTS: The median overall survival (OS) was 12.83 months. Preoperative Karnofsky Performance Score (KPS) and adjuvant radiotherapy were found to be independent clinical parameters influencing the OS by multivariate analysis (p = 0.027 and p < 0.001 respectively). Whereas extent of tumor resection failed to demonstrate statistical significance. For molecular markers, P53 overexpression was identified as a negative prognostic factor for overall survival by multivariate analysis (p = 0.030). CONCLUSION: Low preoperative KPS, absence of radiotherapy and P53 overexpression were identified as predictors of a dismal overall survival in patients with DMG and H3K27M mutations.

Molecular Pathological Markers Correlated With the Recurrence Patterns of Glioma.

PURPOSE: Glioma is one of the most common tumors of the central nervous system, and many patients suffer from recurrence even after standard comprehensive treatment. However, little is known about the molecular markers that predict the recurrence patterns of glioma. This study aimed to demonstrate the correlations between molecular markers and glioma recurrence patterns, which included local/nonlocal recurrence and paraventricular/nonparaventricular recurrence. METHODS: Immunohistochemical techniques were used to assess the molecular markers of 88 glioma tissues following surgical resection. The recurrence patterns were divided into local recurrence, marginal recurrence, distant recurrence, multirecurrence, and subarachniod recurrence, with the last four recurrence patterns being collectively called nonlocal recurrence. According to whether the recurrence invaded ventricles, the nonlocal recurrence patterns were divided into paraventricular and nonparaventricular recurrence. Then, we compared the different recurrence patterns and their clinical characteristics, focusing on the expression of molecular markers. RESULTS: More patients in the nonlocal recurrence group received combined radiotherapy and chemotherapy than patients in the local recurrence group (p=0.019). Sex, age, extent of surgery, time to recurrence, tumor location, size, and WHO grade were not different in the defined groups (P>0.05). Recurrent tumor volume and WHO grade were significantly different between the paraventricular and nonparaventricular recurrence groups (p=0.046 and 0.033). The expression of Ki-67, P53, and PCNA in the nonlocal recurrence group was significantly higher than that in the local recurrence group (p=0.015, 0.009, and 0.037), while the expression of S-100 in the nonlocal recurrence group was significantly lower than that in the local recurrence group (p=0.015). Cox regression indicated hazard ratio (HR) for high expression level of PCNA associated with non-local recurrence was 3.43 (95% CI, 1.15, 10.24), and HR for high expression level of MGMT associated with paraventricular recurrence was 2.64 (95% CI, 1.15,6.08). CONCLUSIONS: Ki-67, P53, PCNA, and MGMT might be important clinical markers for nonlocal recurrence and paraventricular recurrence.

Knockdown of RPL34 inhibits the proliferation and migration of glioma cells through the inactivation of JAK/STAT3 signaling pathway.

Ribosomal protein L34 (RPL34), belonging to the L34E family of ribosomal proteins, was reported to be dysregulated in several types of cancers and plays important roles in tumor progression. However, the expression and roles of RPL34 in human glioma remain largely unknown. Thus, the objective of this study was to investigate the expression and role of RPL34 in glioma. We report here that RPL34 is highly expressed in human glioma tissues and cell lines. Knockdown of RPL34 markedly inhibited the proliferation, migration, and invasion, as well as prevented the epithelial-mesenchymal transition phenotype in glioma cells. Further, mechanistic analysis showed that knockdown of RPL34 significantly downregulated the levels of p-JAK and p-STAT3 in glioma cells. Taken together, our findings indicated that knockdown of RPL34 inhibits the proliferation and migration of glioma cells through the inactivation of JAK/STAT3 signaling pathway. Thus, RPL34 may serve as a potential therapeutic target for the treatment of glioma.

[Analysis of prognostic factors for survival in elderly patients with glioma].

OBJECTIVE: To analyze the prognostic factors for survival in elderly patients with glioma.
 Methods: We performed a retrospective analysis of prognostic factors for elderly patients with glioma, who were treated by the same attending doctor during June 2014 and June 2016, to investigate the correlations of the age, dimension of pathology, histological grade, extent of resection, adjuvant therapy, preoperative Karnofsky Performance Scale (KPS) score, postoperative KPS score, molecular markers [isocitrate dehydrogenase-1 (IDH-1), O6-methylguanine DNA-transferase (MGMT), epidermal growth factor receptor (EGFR), Ki-67] with the prognosis.
 Results: A total of 45 patients were included in the study. The median overall survival (OS) was 11 months. The median progression-free survival (PFS) was 6 months. Univariate analysis revealed that the age, gender, dimension of pathology, histological grade and preoperative KPS score had no significant correlation with survival (P>0.05). The gross total resection, higher postoperative KPS score, adjuvant therapy, lower Ki-67 index were significantly correlated with survival. The expressions of MGMT and EGFR were significant factors for survival. High postoperative KPS score (P=0.019), adjuvant therapy (P=0.024), and the expression of MGMT (P=0.026) were independent predictors for increased median OS in a multivariate regression model.
 Conclusion: The extent of resection, adjuvant therapy, postoperative KPS score and molecular markers are the influential factors for survival. Larger prospective studies are needed to confirm these findings.

Improvement of health related quality of life in patients with recurrent glioma treated with bevacizumab plus daily temozolomide as the salvage therapy.

OBJECTIVES: Bevacizumab (BEV) plus daily temozolomide (TMZ) as a salvage therapy have been recommended to recurrent glioma. The objective of this retrospective study was to evaluate the effect of the combined regimen on health related quality of life (HRQL) and treatment response in patients with recurrent glioma. PATIENTS AND METHODS: Twenty patients with recurrent glioma were treated with BEV (5-10 mg/kg, i.v. every 2 weeks) plus daily TMZ (daily, 50 mg/m2). The treatment response was evaluated via the RANO criteria. HRQL were measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30 (QLQ-C30) and Brain Module (QLQ-BN20). RESULTS: Twenty patients received a total of 85 cycles of BEV with a median number of 4 cycles (range: 2-10). No patients showed complete response (CR) to treatment. Twelve patients had partial response (PR), stable disease (SD) in 5 patients with, and 3 patients showed progressive disease (PD). In the functioning domains of QLQ-C30, physical functioning, cognitive functioning and emotional functioning significantly improved after the second cycle of BEV compared to baseline, with the mean score of 45.0 vs. 64.0 (p = 0.020), 55.8 vs. 71.7 (p = 0.020) and 48.3 vs. 67.5 (p = 0.015), respectively. In the symptom scales, the scores of pain and nausea/vomiting significantly decreased compared to baseline from the mean score of 39.1 to 20.0 (p = 0.020) and 29.2 to 16.7 (p = 0.049), respectively. Score of global health status also increased from 47.5 to 63.3 (p = 0.001). As determined with the QLQ-BN20, motor dysfunction (43.3 vs. 25.0, p = 0.021), weakness of legs (36.7 vs. 18.3, p = 0.049), headache (38.3 vs. 20.0, p = 0.040), and drowsiness (50.0 vs. 30.0, p = 0.026) after the second cycle of BEV also significantly improved compared to baseline. CONCLUSION: BEV plus daily TMZ as a salvage therapy improved HRQL in patients with recurrent glioma.

MicroRNA-302a targets GAB2 to suppress cell proliferation, migration and invasion of glioma.

Glioma is the most frequent and aggressive primary tumor of the brain in humans. Over the last few decades, significant progress has been made in early detection and multi-mode treatments, but the prognosis of gliomas is still extremely poor. MicroRNAs are endogenously expressed non-coding, single strand and short RNA molecules. Increasing number of studies demonstrated that microRNAs are dysregulated in a variety of human cancers, and play significant roles in tumorigenesis and tumor development, including glioma. In the present study, we for the first time found that microRNA-302a (miR-302a) was significantly downregulated in both glioma tissues and cell lines. In glioma patients, low miR-302a expression was correlated with KPS score and WHO grade. Restoration of miR-302a expression inhibited cell proliferation, migration and invasion of glioma in vitro. In addition, GAB2 was identified as a direct target of miR-320a. In clinical glioma tissues, GAB2 was upregulated and in-versely correlated with miR-302a expression. GAB2 underexpression had similar biological roles with miR-302a overexpression in glio-ma cells, further confirming that GAB2 was a functional downstream target of miR-302a. Moreover, rescue experiments showed that upregulation of GAB2 effectively reversed the inhibition effects of miR-302a on glioma cells proliferation, migration and invasion. These findings suggested that miR-302a is an important tumor suppressor of glioma progression by directly targeting GAB2, thus providing new insight into the molecular mechanisms underlying glioma occurrence, development and evolution of glioma.

Quercetin nanoparticles induced autophagy and apoptosis through AKT/ERK/Caspase-3 signaling pathway in human neuroglioma cells: In vitro and in vivo.

Neuroglioma is a complex neuroglial tumor involving dysregulation of many biological pathways at multiple levels. Quercetin is a potent cancer therapeutic agent presented in fruit and vegetables, preventing tumor proliferation, and is a well known cancer therapeutic agent and autophagy mediator. Recent studies showed that drug delivery by nanoparticles have enhanced efficacy with reduced side effects. In this regard, gold-quercetin into poly (dl-lactide-co-glycolide) nanoparticles was examined. In the present study, quercetin nanoparticle induced cell autophagy and apoptosis in human neuroglioma cell was investigated. Quercetin nanoparticle administrated to animals displayed suppressed role in tumor growth. The cell viability was deterined through CCK8 assay. Transmission electron microscopy was utilized to observe the formation of autophagosome. The cell apoptosis was assessed by annexin V-PI staining. The protein expression of cell autophagy regulators and tumor suppressors were analyzed via western blot and RT-PCR. Treatment of human neuroglioma cell with quercetin nanoparticle induced cell death in a dose-and time-dependent manner. The flow cytometry results showed that the proportion of the apoptosis cells had gained after quercetin nanoparticle treatment compared to untreatment group. Moreover, the expression of activated PI3K/AKT and Bcl-2 were down-regulated upon quercetin nanoparticle treatment in human neuroglioma cells. The expression level of LC3 and ERK as well as cytoplasm p53, cleaved Caspase-3 and PARP was positively correlated with the concentration of quercetin nanoparticle. In addition, p-mTOR and GAIP were obviously down-regulated by quercetin nanoparticle treatment in a dose-dependent manner. These results indicated that quercetin nanoparticle could induce autophagy and apoptosis in human neuroglioma cells, the underlying molecular mechanisms, at least partly, through activation LC3/ERK/Caspase-3 and suppression AKT/mTOR signaling.

Copper as an antibacterial agent for human pathogenic multidrug resistant Burkholderia cepacia complex bacteria.

The Burkholderia cepacia complex (Bcc) consists of 17 closely related multidrug resistant bacterial species that are difficult to eradicate. Copper has recently gained attention as an antimicrobial agent because of its inhibitory effects on bacteria, yeast, and viruses. The objective of this study was to evaluate the antibacterial activity of copper surfaces and copper powder against members of the B. cepacia complex. The antibacterial activity of different copper surfaces was evaluated by incubating them with Bcc strain suspensions (5×10(7)cfu/ml). The bacterial survival counts were calculated and the data for various copper surfaces were compared to the data for stainless steel and polyvinylchloride, which were used as control surfaces. The antibacterial activity of copper powder was determined with the diffusimetrical technique and the zone of inhibition was evaluated with paper disks. A single cell gel electrophoresis assay, staining assays, and inductively coupled plasma mass spectroscopy were performed to determine the mechanism responsible for the bactericidal activity. The results showed a significant decrease in the viable bacterial count after exposure to copper surfaces. Moreover, the copper powder produced a large zone of inhibition and there was a significantly higher influx of copper ions into the bacterial cells that were exposed to copper surfaces compared to the controls. The present study demonstrates that metallic copper has an antibacterial effect against Bcc bacteria and that copper adversely affects the bacterial cellular structure, thus resulting in cell death. These findings suggest that copper could be utilized in health care facilities to reduce the bioburden of Bcc species, which may protect susceptible members of the community from bacterial infection.