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.

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.

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.

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.

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.

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.

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.

Genome sequence of the rice-pathogenic bacterium Acidovorax avenae subsp. avenae RS-1.

Acidovorax avenae subsp. avenae is a phytobacterium which is the causative agent of several plant diseases with economic significance. Here, we present the draft genome sequence of strain RS-1, which was isolated from rice shoots in a rice field in China. This strain can cause bacterial stripe of rice.

Genome sequence of the Enterobacter mori type strain, LMG 25706, a pathogenic bacterium of Morus alba L.

Enterobacter mori is a plant-pathogenic enterobacterium responsible for the bacterial wilt of Morus alba L. Here we present the draft genome sequence of the type strain, LMG 25706. To the best of our knowledge, this is the first genome sequence of a plant-pathogenic bacterium in the genus Enterobacter.

Horizontal gene transfer in silkworm, Bombyx mori.

BACKGROUND: The domesticated silkworm, Bombyx mori, is the model insect for the order Lepidoptera, has economically important values, and has gained some representative behavioral characteristics compared to its wild ancestor. The genome of B. mori has been fully sequenced while function analysis of BmChi-h and BmSuc1 genes revealed that horizontal gene transfer (HGT) maybe bestow a clear selective advantage to B. mori. However, the role of HGT in the evolutionary history of B. mori is largely unexplored. In this study, we compare the whole genome of B. mori with those of 382 prokaryotic and eukaryotic species to investigate the potential HGTs. RESULTS: Ten candidate HGT events were defined in B. mori by comprehensive sequence analysis using Maximum Likelihood and Bayesian method combining with EST checking. Phylogenetic analysis of the candidate HGT genes suggested that one HGT was plant-to- B. mori transfer while nine were bacteria-to- B. mori transfer. Furthermore, functional analysis based on expression, coexpression and related literature searching revealed that several HGT candidate genes have added important characters, such as resistance to pathogen, to B. mori. CONCLUSIONS: Results from this study clearly demonstrated that HGTs play an important role in the evolution of B. mori although the number of HGT events in B. mori is in general smaller than those of microbes and other insects. In particular, interdomain HGTs in B. mori may give rise to functional, persistent, and possibly evolutionarily significant new genes.

Enterobacter mori sp. nov., associated with bacterial wilt on Morus alba L.

Two isolates of mulberry-pathogenic bacteria isolated from diseased mulberry roots were investigated in a polyphasic taxonomic study. Comparative 16S rRNA gene sequence analysis combined with rpoB gene sequence analysis allocated strains R18-2(T) and R3-3 to the genus Enterobacter, with Enterobacter asburiae, E. amnigenus, E. cancerogenus, E. cloacae subsp. cloacae, E. cloacae subsp. dissolvens and E. nimipressuralis as their closest relatives. Cells of the isolates were Gram-negative, facultatively anaerobic rods, 0.3-1.0 µm wide and 0.8-2.0 µm long, with peritrichous flagella, showing a DNA G+C content of 55.1 ± 0.5 mol%. Calculation of a similarity index based on phenotypic features and fatty acid methyl ester (FAME) analysis suggested that these isolates are members of E. cancerogenus or E. asburiae or a closely related species. Biochemical data revealed that the isolates could be differentiated from their nearest neighbours by the presence of lysine decarboxylase activity and their ability to utilize d-arabitol. DNA-DNA relatedness also distinguished the two isolates from phylogenetically closely related Enterobacter strains. Based on these data, it is proposed that the isolates represent a novel species of the genus Enterobacter, named Enterobacter mori sp. nov. The type strain is R18-2(T) ( = CGMCC 1.10322(T) = LMG 25706(T)).

[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.

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.

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.

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.

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.

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.

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.